Circulation. 2022 May 23. doi: 10.1161/CIRCULATIONAHA.122.060402. Online ahead of print.

ABSTRACT

Background: Sodium-glucose co-transporter-2 inhibitors (SGLT2i) are foundational therapy in patients with heart failure with reduced ejection fraction (HFrEF), yet underlying mechanisms of benefit are not well defined. We sought to investigate the relationships between SGLT2i treatment, changes in metabolic pathways, and outcomes using targeted metabolomics. Methods: Dapagliflozin Effects on Biomarkers, Symptoms and Functional Status in Patients with HF with Reduced Ejection Fraction (DEFINE-HF) was a placebo-controlled trial of dapagliflozin in HFrEF. We performed targeted mass spectrometry-based profiling of 63 metabolites (45 acylcarnitines [markers of fatty acid oxidation], 15 amino acids, and 3 conventional metabolites) in plasma samples at randomization and 12 weeks. Using mixed models, we identified principal components analysis (PCA)-defined metabolite clusters that changed differentially with treatment, and also examined the relationship between change in metabolite clusters with change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Models were adjusted for relevant clinical covariates, and nominal p<0.05 with FDR-adjusted p-value<0.10 were used to determine statistical significance. Results: Among the 234 DEFINE-HF participants with targeted metabolomic data, the mean age was 62.0±11.1 years, 25% were women, 38% were Black, and mean ejection fraction was 27±8%. Dapagliflozin increased ketone-related and short/medium-chain acylcarnitine PCA metabolite clusters compared with placebo (nominal p=0.01, FDR-adjusted p-value=0.08 for both clusters). However, ketosis (Β-hydroxybutyrate levels > 500 μM), was infrequently achieved (3 [2.5%] in dapagliflozin arm vs. 1 [0.9%] in placebo arm), and supraphysiologic levels were not observed. Conversely, increases in long-chain acylcarnitine, long-chain dicarboxylacylcarnitine, and aromatic amino acid metabolite clusters were associated with decreases in KCCQ scores (i.e. worse quality of life) and increases in NT-proBNP levels, without interaction by treatment group. Conclusions: In this study of targeted metabolomics in a placebo-controlled trial of SGLT2i in HFrEF, we observed effects of dapagliflozin on key metabolic pathways, supporting a role for altered ketone and fatty acid biology with SGLT2i in patients with HFrEF. Reassuringly, only physiologic levels of ketosis were observed. Additionally, we identified several metabolic biomarkers associated with adverse HFrEF outcomes.

PMID:35603596 | DOI:10.1161/CIRCULATIONAHA.122.060402

Saudi J Biol Sci. 2022 Jun;29(6):103302. doi: 10.1016/j.sjbs.2022.103302. Epub 2022 Apr 22.

ABSTRACT

In tropical and sub-tropical areas of the world the most damaging pest of the livestock sector are cattle tick, Rhipicephalus microplus. The current study was aimed to generate phytochemical derived acaricides to control Rhipicephalus microplus populations, to maintain livestock herd production, minimize economic losses and to reduce uses of man-made chemicals acaricides. To achieve this goal, Adult immersion and larval package test were used to determine the feasibility of Berberium lyceum and Tamarixa aphylla against Rhipicephalus microplus ticks. Further, an In silico technique was employed to discover biologically active substances from both plants using docking method. Berberium lyceum and Tamarixa aphylla exhibited a reasonably high fatal effect at 40.0 mg/L on egg laying (index of egg laying = 0.19 and 0.19) respectively, thus inhibiting the oviposition (49.5 and 45.1, respectively) and the larval mortality (97% and 93%, respectively). Further, we also used Chem-Draw ultra-software (v. 12.0.2.1076. 2010) to illustrate different structures of38 known bioactive phytochemicals which are discovered in the PubChem database and verify the hypothesis that tick inhibition was linked to acetylcholinesterase (AChE). Barbamunine and rutin from Berberium lyceum showed remarkable interaction with RmAChE1 active site residues with docking scores of -9.11 to -8.71 while phytol and dehydrodigallic acid from Tamarix aphylla showed comparable docking scores of -7.17 and -7.14 respectively against Rhipicephalus microplus acetylcholinesterase protein. Based on obtained result, we believe that Berberium lyceum and Tamarixa aphylla bioactive components could be potential candidates in the control and management of Rhipicephalus microplus and should be studied further as a supplement or replacement for synthetic acaricides.

PMID:35602870 | PMC:PMC9118158 | DOI:10.1016/j.sjbs.2022.103302

Cureus. 2022 Apr 18;14(4):e24250. doi: 10.7759/cureus.24250. eCollection 2022 Apr.

ABSTRACT

Hepatic injury due to dietary and herbal supplements can often share similar clinical characteristics with autoimmune hepatitis (AIH). Sambucus species, commonly known as elderberry, have been used in traditional medicine for centuries to prevent and treat respiratory problems. Although there are no clear reports on the association of elderberry with AIH or drug-induced hepatitis, there have been concerns about negative health manifestations linked to elderberry and the overproduction of inflammatory cytokines. In this article, we discuss a case of a patient who developed autoimmune hepatitis while on long-term elderberry-containing supplements and a probable association between the two.

PMID:35602846 | PMC:PMC9116981 | DOI:10.7759/cureus.24250

Cureus. 2022 Apr 17;14(4):e24225. doi: 10.7759/cureus.24225. eCollection 2022 Apr.

ABSTRACT

Introduction Malnutrition among women of reproductive age (WRA), especially those living in slum areas, is one of the most concerning nutritional issues because of the extreme nutritional stress they face in the form of inequitable intra-household food distribution (IHFD). This study aimed to assess the nutritional status (NS) and its association with IHFD among reproductive-age-group women along with exploring the perspectives of the stakeholders regarding inequitable food distribution. Materials and methods The quantitative part of the convergent parallel mixed-methods design study was conducted among 150 WRA, selected by cluster random sampling from 15 slum areas of Hooghly District, between December 2020 and May 2021. Data were collected using a predesigned pretested schedule with anthropometric measurements. IHFD was quantified by the relative dietary energy adequacy ratio (RDEAR). Ordinal logistic regression was performed to obtain adjusted-proportional odds ratios (aPOR) for higher categories of NS (underweight: reference category). Stratified subgroup analysis was done to assess the influencers of IHFD. For the qualitative part, in-depth interviews were conducted with eight purposively selected in-laws of study participants, and the data were interpreted by thematic analysis. Results The mean age of the study participants was 28.6±6.3 years. The proportion of malnutrition and inequitable IHFD (RDEAR<1) among them was 50% and 46%, respectively. Higher categories of NS were found to be significantly associated with an increase in RDEAR (aPOR=22.6, 95% CI: 2.75-185.45, p-value=0.004). Among underweight and normal NS women, those who were earning members and directly involved in food preparation/production had a greater allocation of food within their households. Physiological intolerance, incapacity of earning, and traditional customs were the most recurring themes transcribed as the barriers to equitable food distribution. Conclusion A high magnitude of malnutrition and its association with inequitable IHFD among WRA warrant policy-level support to increase women's employment opportunities and address gender-based inequities through comprehensive information education communication (IEC) techniques as well.

PMID:35602827 | PMC:PMC9117825 | DOI:10.7759/cureus.24225

Inf Serv Use. 2022 Apr 26;41(3-4):293-314. doi: 10.3233/ISU-210130. eCollection 2021.

ABSTRACT

The U.S. National Library of Medicine (NLM) exhibition known as Native Voices reflected Donald A.B. Lindberg M.D.'s keen and long-held desire to help improve public understanding of Native American health challenges and honor the culture, tradition, and healing ways of Native Peoples. A centerpiece of the exhibition was a large set of video interviews that Dr. Lindberg conducted with Native health and community leaders. Dr. Lindberg and his team engaged Native advisors in the exhibition development; sought Native input through Listening Circles, Tribal Consultations; and site visits, and made the video interviews accessible via interactive kiosks and iPads. For its time, this was state-of-the-art exhibition technology. The exhibition also included Native artifacts and art works to complement the videos, including a scale model of the iconic Hokule'a Native Hawaiian voyaging canoe, and a full-size Lummi Indian healing totem pole. The totem journeyed across the U.S. prior to its installation next to the NLM herbal garden in Bethesda, MD. A traveling version of the exhibition visited more than 130 venues in 40 States across the U.S. The interview clips and other content are accessible on the exhibition website, and the full-length interviews are retained in the NLM permanent video collection.

PMID:35602563 | PMC:PMC9071794 | DOI:10.3233/ISU-210130

Front Med (Lausanne). 2022 May 4;9:822870. doi: 10.3389/fmed.2022.822870. eCollection 2022.

ABSTRACT

Aristolochic acid nephropathy (AAN) is a progressive tubulointerstitial nephritis caused by the intake of aristolochic acids (AA) contained in Chinese herbal remedies or contaminated food. AAN is characterized by tubular atrophy and interstitial fibrosis, characterizing advanced kidney disease. It is established that sustained or recurrent acute kidney injury (AKI) episodes contribute to the progression of CKD. Therefore, the study of underlying mechanisms of AA-induced nephrotoxicity could be useful in understanding the complex AKI-to-CKD transition. We developed a translational approach of AKI-to-CKD transition by reproducing human AAN in rodent models. Indeed, in such models, an early phase of acute tubular necrosis was rapidly followed by a massive interstitial recruitment of activated monocytes/macrophages followed by cytotoxic T lymphocytes, resulting in a transient AKI episode. A later chronic phase was then observed with progressive tubular atrophy related to dedifferentiation and necrosis of tubular epithelial cells. The accumulation of vimentin and αSMA-positive cells expressing TGFβ in interstitial areas suggested an increase in resident fibroblasts and their activation into myofibroblasts resulting in collagen deposition and CKD. In addition, we identified 4 major actors in the AKI-to-CKD transition: (1) the tubular epithelial cells, (2) the endothelial cells of the interstitial capillary network, (3) the inflammatory infiltrate, and (4) the myofibroblasts. This review provides the most comprehensive and informative data we were able to collect and examines the pending questions.

PMID:35602498 | PMC:PMC9115860 | DOI:10.3389/fmed.2022.822870

Oxid Med Cell Longev. 2022 May 12;2022:4139330. doi: 10.1155/2022/4139330. eCollection 2022.

ABSTRACT

Ischemic stroke, a cerebrovascular disease worldwide, triggers a cascade of pathophysiological events, including blood-brain barrier (BBB) breakdown. Brain microvascular endothelial cells (BMECs) play a vital role in maintaining BBB function. The injury of BMECs may worsen neurovascular dysfunction and patients' prognosis. Therefore, uncover the principal molecular mechanisms involved in BBB disruption in stroke becomes pressing. The endocannabinoid system (ECS) has been implicated in increasingly physiological functions, both in neurometabolism and cerebrovascular regulation. Modulating its activities by the fatty acid amide hydrolase (FAAH) shows anti-inflammatory characteristics. Andrographolide (AG), one Chinese herbal ingredient, has also attracted attention for its role in immunomodulatory and as a therapeutic target in BBB disorders. Recently, the FAAH inhibitor URB597 and AG have important regulatory effects on neuronal and vascular cells in ischemia. However, the effects of URB597 and AG on BMEC permeability and apoptosis in oxygen-glucose deprivation (OGD) and the underlying mechanisms remain unclear. To address these issues, cultured BMECs (bEnd.3 cells) were exposed to OGD. The cell viability, permeability, tube formation, and apoptosis were assessed following treatment with URB597, AG, and cotreatment. Mitochondrial membrane potential (MMP), reactive oxygen species (ROS), superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), proinflammatory factors, tight junction (TJ) proteins, and oxidative stress-mediated Nrf2 signaling were also investigated. Results revealed that OGD broke the endothelial barrier, cell viability, MMP, and tube formation, which was reversed by URB597 and AG. OGD-induced enhancement of ROS, MDA, and apoptosis was reduced after drug interventions. URB597 and AG exhibited antioxidant/anti-inflammatory and mitochondrial protective effects by activating Nrf2 signaling. These findings indicated that URB597 and AG protect BMECs against OGD-induced endothelial permeability impairment and apoptosis by reducing mitochondrial oxidative stress and inflammation associated with activation of Nrf2 signaling. URB597 and AG showing the vascular protection may have therapeutic potential for the BBB damage in ischemic cerebrovascular diseases.

PMID:35602108 | PMC:PMC9119762 | DOI:10.1155/2022/4139330

Oxid Med Cell Longev. 2022 May 13;2022:2427802. doi: 10.1155/2022/2427802. eCollection 2022.

ABSTRACT

OBJECTIVES: Acute kidney injury (AKI) is a loose set of kidney diseases accompanied by a variety of syndromes, which is a serious threat to human life and health. Some alkaloids are derived from various Chinese herbs have been widely concerned in the improvement of AKI. This review provides the research progress of alkaloids in AKI experimental models and discusses the related molecular mechanisms. Key Findings. Alkaloids can protect AKI through various mechanisms including antioxidant stress, improvement of mitochondrial damage, reduction of cell death, induction of autophagy, and inhibition of inflammation. These mechanisms are mainly related to the activation of Nrf2/HO-1 signaling pathway, inhibition of ferroptosis and apoptosis, regulation of PINK1/Parkin pathway, inhibition of TLR4/NF-κB pathway and NLRP3 inflammatory bodies, upregulation of Klotho protein level and so on. In addition, there are a few alkaloids that have certain toxicity on the kidney.

CONCLUSION: Alkaloids have been shown to significantly improve AKI, but only in pharmacological studies. This paper summarizes the main experimental models currently used in AKI research and describes some representative alkaloids based on recent research. Their potential roles in the prevention and treatment of AKI through different mechanisms are highlighted.

PMID:35602100 | PMC:PMC9122709 | DOI:10.1155/2022/2427802

Vet Res Forum. 2022 Mar;13(1):7-14. doi: 10.30466/vrf.2020.118949.2814. Epub 2022 Mar 15.

ABSTRACT

At the present time cancer is one of the biggest health problems and because of the problems encountered in its treatment, alternative treatment methods of herbal origin are researched. In this study, the cytotoxic effects of the essential oil extracted from the Micromeria congesta plant on various cancer cells (A549, ECC-1, HCT-116, HELA, HGC-27, MDA-MB-231, SNU-423, U20S, DLD-1, PC-3) and normal cells (BEAS-2B, CRL-4010) have been examined. Anticancer mechanism of action has been particularly examined on gastric cancer (HGC-27; IC50: 15.84 µg mL^-1), on which essential oil showed a high cytotoxic effect. In the study, the cytotoxic effect and the apoptotic effect have been applied by MTT and flow cytometric annexin-V methods, respectively. The apoptotic gene expression (caspase 3, caspase 9, MMP2, MMP9, ACTB) real-time PCR content analysis has been performed with gas chromatography mass spectrometry (GC-MS). M. congesta essentials oil has the highest cytotoxic effect on gastric cancer (HGC-27) cells, decreases MMP2 and MMP9 expressions, and induces apoptosis with increasing the expression of caspase 3 and caspase 8 genes. In addition, it has been determined that piperitenone oxide (40.00 - 45.00%), pulegone (11.00%) and cyclohexanone (18.00 - 19.00%) are the major components of M. congesta essentials oil. In conclusion, it has been determined that the compounds found in high amounts in M. congesta plant induces apoptosis by affecting the expression of compound genes and thus can have the potential to be an alternative drug in the treatment of gastric cancer.

PMID:35601780 | PMC:PMC9094590 | DOI:10.30466/vrf.2020.118949.2814

Helminthologia. 2022 May 4;59(1):37-45. doi: 10.2478/helm-2022-0005. eCollection 2022 Mar.

ABSTRACT

Trichinellosis is a nematode-causing disease distinguished by its continuous transmission in the carnivores and omnivores. Despite effective eradication of the enteral forms, conventional drugs fail to eliminate the migrating and muscle ones. Over the past years, researchers intensified the work on herbal medicines as alternatives or aids to albendazole, the reference drug. This research hypothesizes that the therapeutic agent absorption route could be an evidence-based carrier molecule or auxiliary drug to albendazole. Accordingly, this in vitro study was designed to investigate mainly the phenotypic changes induced by a mono-treatment of albendazole, Lipidium sativum (garden cress), and Commiphora molmol (myrrh). Incredibly, no data were reported on the morphological alterations of T. spiralis larvae treated by any of these drugs. The experimental design tested various concentrations (25, 50, 100, and 200 μg/ml) of each herbal medicine for the lethal effects on the parasite forms for a day (1, 12, and 24h). The data showed that the highest significant mortality rate of the parasite forms was in favor of the concentration 200 μg/ml of both plant extracts in a time-dependent manner. Therefore, albendazole at 200 μg/ml dose was tested in parallel, and all experimental groups were compared to non-treated muscle larvae and worms. Albendazole-treated worms accounted for the least significant (p<0.001) survival rate (2 %), followed by myrrh (5 %), and the adverse was valid for the survival rate of the muscle larvae at that time. None of the larvae/worms was alive after 24 hours of incubation with the 200μg/ml of either treatment. The scanning electron microscope investigation of the experimental groups provided a shred of evidence for different routes of taking up the candidate drugs by the parasite. In conclusion, the results of the previous work in vivo and current in vitro study recommend myrrh over garden cress as a complementary agent of albendazole.

PMID:35601763 | PMC:PMC9075874 | DOI:10.2478/helm-2022-0005

Nutr Metab Insights. 2022 May 17;15:11786388221098507. doi: 10.1177/11786388221098507. eCollection 2022.

ABSTRACT

We explored the benefits of a digitized bedside terminal with a touchscreen for selectable hospital meals called "à la carte digital-select" in cancer chemotherapy patients. The subjects used "à la carte digital-select" for 35 days, from November to December 2015. On average, 253 (between 196 and 288) patients accessed this system per day, and 40 patients used it daily (15.9%). Subjects included 75 patients (cancer chemotherapy: chem-digital-select patients, female: 47) and 12 patients (concurrent chemo radiotherapy: CRT-digital-select patients, female: 6) with a repeat rate of 87% (65) and 100% (12). The average length of hospital stay in chem-digital-select patients was 6 days (1-35), the average number of days using "à la carte digital-select" was 3 days (1-24); a correlation was observed between these factors (r = .80; P < .01). The eating rate of chemotherapy patients and CRT-digital-select patients was high (81%, 81%), and no differences were observed between the rate in the cisplatin group (80%) with 28 patients, the non-cisplatin group (81%) with 47 patients, CRT-digital-select patients (81%) with 12 patients (P = .59; ANOVA). Registered dietitians provided no nutritional intervention in any of the cases. We found that "à la carte digital-select" can contribute to supporting cancer chemotherapy and the dietary needs of cancer patients undergoing chemotherapy.

PMID:35601408 | PMC:PMC9118450 | DOI:10.1177/11786388221098507

JGH Open. 2022 Apr 28;6(5):324-329. doi: 10.1002/jgh3.12744. eCollection 2022 May.

ABSTRACT

BACKGROUND AND AIM: The present study aimed to compare the utility and safety of the colonic self-expandable metallic stent between patients with obstructive primary colorectal cancer who underwent chemotherapy or palliative treatment care and patients bridging for surgery.

METHODS: The cases of 71 patients with colonic obstructive stenosis and in-dwelling stents who were hospitalized between May 2012 and April 2020 at Karatsu Red Cross Hospital were retrospectively analyzed. The patients were classified into three groups: bridging for curative surgery (group I), receiving systemic chemotherapy (group II-A), and receiving only palliative treatment (group II-B). Technical and clinical success rates and complication rates after stenting were evaluated.

RESULTS: No significant differences were observed in the technical (procedure) success rates (group I: 100%; group II, 97.6% [II-A: 100%; II-B: 95.8%]). The total clinical success rate was 85.9% (61/71) and did not vary significantly among the groups (group I: 82.8%; group II 88.0% [II-A: 83.3%; II-B: 91.6%]). No significant differences were observed in the early complication rates between groups I and II and in the late complication rates between groups II-A and II-B. Nutrition status, general condition, tumor staging, and 1-year survival were poorer in group II than in group I.

CONCLUSION: The findings show that colonic stenting for malignant obstruction was performed successfully and safely both in patients who received systemic chemotherapy or palliative therapy and in patients bridging for curative surgery, regardless of risk status for malnutrition, poor general condition, cancer stage progression, and short survival.

PMID:35601122 | PMC:PMC9120876 | DOI:10.1002/jgh3.12744

Evid Based Complement Alternat Med. 2022 May 12;2022:8831750. doi: 10.1155/2022/8831750. eCollection 2022.

ABSTRACT

METHODS: We conducted a literature search on the bioactive components of medicinal plants and their effects on angiogenesis after MI. We searched for articles in Web of Science, MEDLINE, PubMed, Scopus, Google Scholar, and China National Knowledge Infrastructure databases before April 2021.

RESULTS: In this article, we summarized the mechanisms by which copper ions, microRNA, Akt1, inflammation, oxidative stress, mitochondria, and pericytes are involved in angiogenesis after myocardial infarction. In addition, we reviewed the angiogenic effects of natural herbal medicines such as Salvia miltiorrhiza Bunge Bunge, Carthamus tinctorius L., Pueraria lobata, Astragalus, Panax ginseng C.A. Mey., Panax notoginseng (Burkill) F.H. Chen, Cinnamomum cassia (L.) J. Presl, Rehmannia glutinosa (Gaertn.) DC., Leonurus japonicus Houtt, Scutellaria baicalensis Georgi., and Geum macrophyllum Willd.

CONCLUSIONS: Some herbs have the effect of promoting angiogenesis. In the future, natural proangiogenic drugs may become candidates for the treatment of cardiovascular diseases.

PMID:35600953 | PMC:PMC9119779 | DOI:10.1155/2022/8831750

Evid Based Complement Alternat Med. 2022 May 11;2022:3821345. doi: 10.1155/2022/3821345. eCollection 2022.

ABSTRACT

Gosha-jinki-gan (GJG) and Keishi-bukuryo-gan (KBG) are Kampo traditional herbal prescriptions used for different clinical patterns (sho) that improve blood flow. The pharmacological basis of the therapeutic choice remains unclear, although the clinical reliance of this pattern-based therapy is widely proven. We aimed to investigate their effects on microcirculation and nitric oxide (NO) kinetics using a live-imaging system to provide evidence for this. Live-imaging was performed in murine subcutaneous vessels and rat mesentery. In the subcutaneous vessels, we analyzed the effects of both drugs on the vessel diameter, blood flow velocity, and volume in the arteries, arterioles, and capillaries. In the rat mesentery, we induced the "oketsu" blood stasis using a stack of thin vinylidene chloride films and examined the effect on NO production using a fluorescent diaminofluorescein-2 diacetate. Following dissolution in hot water, 300 mg/kg of both drugs were administered intragastrically via a transesophageal catheter. Live-imaging analysis of subcutaneous blood flow revealed the different effects of GJG and KBG on their target vessels and effect onset. GJG targeted the capillaries and progressively increased the blood flow velocity and rate at 30-120 min after administration. No vasodilation or increased blood flow in the arteries and arterioles occurred. In contrast, KBG increased the diameter of the arterioles and arteries at 30-90 min after administration, and increased blood flow velocity and rate in arteries and arterioles. In a model of oketsu blood stasis in the mesenteric arteries, KBG increased the NO production from the vascular endothelial cells with dilatation of the arteriolar diameter. GJG improved blood flow mainly in the capillaries. Endothelial NO production decreased after GJG administration. The empirical treatment choice between GJG and KBG is based on the difference in target vessels and NO action and provides a pharmacological basis for therapy based on traditional medicine.

PMID:35600944 | PMC:PMC9117033 | DOI:10.1155/2022/3821345

Evid Based Complement Alternat Med. 2022 May 12;2022:5318117. doi: 10.1155/2022/5318117. eCollection 2022.

ABSTRACT

OBJECTIVE: The aim of this work was to evaluate the antioxidant potential of Datura metel.

MATERIALS AND METHODS: Heart failure was induced in the frog's heart by continuous perfusion of hydrogen peroxide. Survival time and some heart tissue parameters of oxidative stress were recorded in the presence of aqueous extracts of the leaves and seeds of Datura metel. Ascorbic acid was used as a reference drug.

RESULTS: H₂O₂-enriched Ringer's solution inhibited the negative inotropic and chronotropic effects of acetylcholine, indicating the desensibilization of muscarinic receptors due to H₂O₂-induced oxidative stress. These hearts had a relatively short survival time (14 minutes). In the presence of the aqueous extract of the leaves and seeds of Datura metel (1.5 and 2.5 mg/mL), the time necessary to cause the cardiac arrest was extended to 35 and 37 minutes, respectively, versus 29 minutes for ascorbic acid and 14 minutes for H₂O₂. Furthermore, antioxidant parameters (MDA, SOD, and CAT) were significantly improved in plant extract-treated hearts, compared to peroxidized hearts.

CONCLUSION: Aqueous extract of the leaves and seeds of D. metel can extend heart survival time through antioxidant mechanisms.

PMID:35600941 | PMC:PMC9119793 | DOI:10.1155/2022/5318117

Biochem Biophys Rep. 2022 May 14;30:101280. doi: 10.1016/j.bbrep.2022.101280. eCollection 2022 Jul.

ABSTRACT

The ability of organisms to sense their nutritional environment and adjust their behavior accordingly is critical for survival. Insulin-like peptides (ilps) play major roles in controlling behavior and metabolism; however, the tissues and cells that insulin acts on to regulate these processes are not fully understood. In the fruit fly, Drosophila melanogaster, insulin signaling has been shown to function in the fat body to regulate lipid storage, but whether ilps act on the fly brain to regulate nutrient storage is not known. In this study, we manipulate insulin signaling in defined populations of neurons in Drosophila and measure glycogen and triglyceride storage. Expressing a constitutively active form of the insulin receptor (dInR) in the insulin-producing cells had no effect on glycogen or triglyceride levels. However, activating insulin signaling in the Drosulfakinin (Dsk)-producing neurons led to triglyceride accumulation and increased food consumption. The expression of ilp2, ilp3 and ilp5 was increased in flies with activated insulin signaling in the Dsk neurons, which along with the feeding phenotype, may cause the triglyceride storage phenotypes observed in these flies. In addition, expressing a constitutively active dInR in Dsk neurons resulted in decreased sleep in the fed state and less starvation-induced sleep suppression suggesting a role for insulin signaling in regulating nutrient-responsive behaviors. Together, these data support a role for insulin signaling in the Dsk-producing neurons for regulating behavior and maintaining metabolic homeostasis.

PMID:35600902 | PMC:PMC9115315 | DOI:10.1016/j.bbrep.2022.101280

Front Pharmacol. 2022 May 5;13:765226. doi: 10.3389/fphar.2022.765226. eCollection 2022.

ABSTRACT

Objectives: Pharmacoeconomics evaluation (PE) is increasingly used in the healthcare decision-making process in China. Little is known about PE conducted in Chinese Herbal Medicines (CHMs). We aimed to systematically review trends, characteristics, and quality of PE of CHMS. Methods: We systematically searched both Chinese (CNKI, WanFang, and VIP) and English (Pubmed) databases. Studies were included if they were PE studies comparing both costs and outcomes between two or more interventions published in Chinese or English. Assessment of the quality of studies was conducted using the Quality of Health Economic Analyses (QHES) instrument. T-test and Chi-square tests were used to compare the studies before and after the first edition of China Guidelines for PE published in 2011, and between studies published in Chinese and English. Results: A total of 201 articles were included. There was an increasing trend of PE studies on CHMs during the study period. The top three studied diseases were central nervous system (CNS), mental, and behavioral disorders; cardiovascular diseases; and blood, immune and endocrine diseases. The average QHES score for the included studies was 63.37. Cost-effectiveness analysis (CEA) accounted for the majority (76.6%) of the included studies. Only a quarter of the articles (27.4%) were funded, and there were significantly more studies funded after the publication of China guidelines for PE. About 96.5% of studies did not specify evaluation perspectives and 89.6% of studies had a sample size of less than 300. Around half of the studies (55%) used incremental analysis, but only a few of them considered using a threshold. Half of the studies lacked sensitivity analysis. There was no significant improvement in the quality of studies published after the publication of China Guidelines for PE, and English articles had significantly higher quality than Chinese articles. Conclusion: This study identified several problems in PE studies on CHMs, including having small sample sizes, lacking necessary research elements, and using single evaluation methods. The quality of PE studies on CHMs was not sufficient. Researchers need to understand the standardized way to conduct PE studies and improve the quality and level of PE studies on CHMs.

PMID:35600881 | PMC:PMC9117622 | DOI:10.3389/fphar.2022.765226

Front Pharmacol. 2022 May 4;13:878371. doi: 10.3389/fphar.2022.878371. eCollection 2022.

ABSTRACT

Chronic pain is common and debilitating in cancer survivors. Tibetan herbal pain-relieving plaster is used as an external analgesic to treat musculoskeletal pain in China; however, its safety and efficacy have not been evaluated via clinical trials in cancer survivors. We designed this Phase II randomized, double-blind, placebo-controlled trial (ClinicalTrials.gov Identifier: NCT04916249) to assess the efficacy and safety of the pain-relieving plaster for temporary pain relief among cancer survivors with chronic musculoskeletal pain. Under ethical approval from the Institutional Review Board at the Memorial Sloan Kettering Cancer Center, we will enroll eligible cancer survivors who have a clinical diagnosis of moderate to severe chronic musculoskeletal pain in this study. We use a central randomization system to allocate the eligible participants to either the treatment or the control group in a 1:1 ratio, with stratification by baseline opioid use. We will instruct the participants to apply the herbal patch (Tibetree Pain-Relieving Plaster, Tibet Cheezheng Tibetan Medicine Co. Ltd., Tibet, China) or placebo patch daily at the focal area with worst pain for 14 consecutive days. Study physician, participant, outcome assessor, and biostatistician are blinded to the group allocation. The primary outcome is pain severity measured by the Brief Pain Inventory on Days 2-7. Secondary outcomes include changes in insomnia, anxiety, depression, fatigue, pressure pain threshold, pain medication use, and global impression of change. We will also monitor the adverse events throughout the study period. Statistical analysis will follow the intention-to-treat principle and linear mixed modeling will be used. With rigorous design and implementation, this randomized, placebo-controlled trial will provide the initial evidence on the efficacy and safety of the pain-relieving plaster for pain relief among cancer survivors with chronic musculoskeletal pain.

PMID:35600872 | PMC:PMC9114465 | DOI:10.3389/fphar.2022.878371

Front Pharmacol. 2022 May 5;13:889799. doi: 10.3389/fphar.2022.889799. eCollection 2022.

ABSTRACT

Primary liver cancer (PLC) is one of the most common solid malignancies. However, PLC drug development has been slow, and first-line treatments are still needed; thus, studies exploring and developing alternative strategies for effective PLC treatment are urgently needed. Chinese herbal medicine (CHM) has long been applied in the clinic due to its advantages of low toxicity and targeting of multiple factors and pathways, and it has great potential for the development of novel natural drugs against PLC. Purpose: This review aims to provide an update on the pharmacological mechanisms of Chinese patent medicines (CPMs) and the latest CHM-derived compounds for the treatment of PLC and relevant clinical evaluations. Materials and Methods: A systematic search of English literature databases, Chinese literature, the Clinical Trials Registry Platform, and the Chinese Clinical Trial Registry for studies of CHMs for PLC treatment was performed. Results: In this review, we summarize the clinical trials and mechanisms of CPMs for PLC treatment that have entered the clinic with the approval of the Chinese medicine regulatory authority. These CPMs included Huaier granules, Ganfule granules, Fufang Banmao capsules, Jinlong capsules, Brucea javanica oil emulsions, and compound kushen injections. We also summarize the latest in vivo, in vitro, and clinical studies of CHM-derived compounds against PLC: icaritin and ginsenoside Rg3. Dilemmas facing the development of CHMs, such as drug toxicity and low oral availability, and future developments are also discussed. Conclusion: This review provides a deeper the understanding of CHMs as PLC treatments and provides ideas for the development of new natural drugs against PLC.

PMID:35600861 | PMC:PMC9117702 | DOI:10.3389/fphar.2022.889799

Front Pharmacol. 2022 May 5;13:854292. doi: 10.3389/fphar.2022.854292. eCollection 2022.

ABSTRACT

Aims: The objective of this study was to assess the efficacy and potential mechanisms of Chinese herbal medicine (CHM) for treating coronary heart disease (CHD) patients with anxiety or depression. Methods: A systematic literature search was performed. Screening studies, extracting data, and assessing article quality were carried out independently by two researchers. The active ingredients of CHM for the treatment of CHD with anxiety or depression were analyzed by the network pharmacology, and the main potential mechanisms were summarized by the database of Web of Science. Results: A total of 32 studies were included. The results showed that compared with the blank control groups, CHM was more beneficial in treating anxiety or depression in patients with CHD [anxiety: OR = 3.22, 95% CI (1.94, 5.35), p < 0.00001, I² = 0%; depression: OR = 3.27, 95% CI (1.67, 6.40), p = 0.0005, I² = 0%], and the efficacy of CHM was not inferior to that of Western medicine (WM) [anxiety: OR = 1.58, 95%CI (0.39, 6.35), p = 0.52, I² = 67%; depression: OR = 1.97, 95%CI (0.73, 5.28), p = 0.18, I² = 33%,]. Additionally, CHM also showed a significant advantage in improving angina stability (AS) in CHD patients with anxiety or depression compared with blank groups [anxiety: SMD = 0.55, 95%CI (0.32, 0.79), p < 0.00001, I² = 0%; depression: p = 0.004] and WM groups [anxiety: SMD = 1.14, 95%CI (0.80, 1.47), p < 0.00001, I² = 0%; depression: SMD = 12.15, 95%CI (6.07, 18.23), p < 0.0001, I² = 0%]. Angina frequency (AF) and electrocardiogram (ECG) analysis after using CHM demonstrated similar trends. Based on the network pharmacology, quercetin, kaempferol, luteolin, beta-sitosterol, puerarin, stigmasterol, isorhamnetin, baicalein, tanshinone IIa, and nobiletin were most closely and simultaneously related to the pathological targets of CHD, anxiety, and depression. The main underlying mechanisms might involve anti-damage/apoptosis, anti-inflammation, antioxidative stress, and maintaining neurotransmitter homeostasis. Conclusion: CHM exhibited an obvious efficacy in treating CHD patients with anxiety or depression, especially for improving the symptom of angina pectoris. The most active compounds of CHM could simultaneously act on the pathological targets of CHD, anxiety, and depression. Multiple effective components and multiple targets were the advantages of CHM compared with WM.

PMID:35600859 | PMC:PMC9117623 | DOI:10.3389/fphar.2022.854292

J Ginseng Res. 2022 May;46(3):496-504. doi: 10.1016/j.jgr.2021.12.008. Epub 2021 Dec 22.

ABSTRACT

BACKGROUND: Cigarette smoke (CS) is considered a principal cause of chronic obstructive pulmonary disease (COPD) and is associated with mucus hypersecretion and airway inflammation. Ginsenoside compound K (CK), a product of ginsenoside metabolism, has various biological activities. Studies on the effects of CK for the treatment of COPD and mucus hypersecretion, including the underlying signaling mechanism, have not yet been conducted.

METHODS: To study the protective effects and molecular mechanism of CK, phorbol 12-myristate 13-acetate (PMA)-induced human airway epithelial (NCI-H292) cells were used as a cellular model of airway inflammation. An experimental mouse COPD model was also established via CS inhalation and intranasal administration of lipopolysaccharide. Mucin 5AC (MUC5AC), monocyte chemoattractant protein-1, tumor necrosis factor-α (TNF-α), and interleukin-6 secretion, as well as elastase activity and reactive oxygen species production, were determined through enzyme-linked immunosorbent assay. Inflammatory cell influx and mucus secretion in mouse lung tissues were estimated using hematoxylin and eosin and periodic acid-schiff staining, respectively. PKCδ and its downstream signaling molecules were analyzed via western blotting.

RESULTS: CK prevented the secretion of MUC5AC and TNF-α in PMA-stimulated NCI-H292 cells and exhibited a protective effect in COPD mice via the suppression of inflammatory mediators and mucus secretion. These effects were accompanied by an inactivation of PKCδ and related signaling in vitro and in vivo.

CONCLUSION: CK suppressed pulmonary inflammation and mucus secretion in COPD mouse model through PKC regulation, highlighting the compound's potential as a useful adjuvant in the prevention and treatment of COPD.

PMID:35600779 | PMC:PMC9120799 | DOI:10.1016/j.jgr.2021.12.008

J Ginseng Res. 2022 May;46(3):408-417. doi: 10.1016/j.jgr.2021.07.003. Epub 2021 Jul 12.

ABSTRACT

BACKGROUND: Korean Red Ginseng extract (KRGE) has been used as a health supplement and herbal medicine. Astrocytes are one of the key cells in the central nervous system (CNS) and have bioenergetic potential as they stimulate mitochondrial biogenesis. They play a critical role in connecting the brain vasculature and nerves in the CNS.

METHODS: Brain samples from KRGE-administered mice were tested using immunohistochemistry. Treatment of human brain astrocytes with KRGE was subjected to assays such as proliferation, cytotoxicity, Mitotracker, ATP production, and O₂ consumption rate as well as western blotting to demonstrate the expression of proteins related to mitochondria functions. The expression of hypoxia-inducible factor-1α (HIF-1α) was diminished utilizing siRNA transfection.

RESULTS: Brain samples from KRGE-administered mice harbored an increased number of GFAP-expressing astrocytes. KRGE triggered the proliferation of astrocytes in vitro. Enhanced mitochondrial biogenesis induced by KRGE was detected using Mitotracker staining, ATP production, and O₂ consumption rate assays. The expression of proteins related to mitochondrial electron transport was increased in KRGE-treated astrocytes. These effects were blocked by HIF-1α knockdown. The factors secreted from KRGE-treated astrocytes were determined, revealing the expression of various cytokines and growth factors, especially those related to angiogenesis and neurogenesis. KRGE-treated astrocyte conditioned media enhanced the differentiation of adult neural stem cells into mature neurons, increasing the migration of endothelial cells, and these effects were reduced in the background of HIF-1α knockdown.

CONCLUSION: Our findings suggest that KRGE exhibits prophylactic potential by stimulating astrocyte mitochondrial biogenesis through HIF-1α, resulting in improved neurovascular function.

PMID:35600778 | PMC:PMC9120627 | DOI:10.1016/j.jgr.2021.07.003

J Ginseng Res. 2022 May;46(3):435-443. doi: 10.1016/j.jgr.2021.08.002. Epub 2021 Aug 10.

ABSTRACT

BACKGROUND: Post-traumatic stress disorder (PTSD) is a psychiatric disease that develops following exposure to a traumatic event and is a stress-associated mental disorder characterized by an imbalance of neuroinflammation. Korean Red Ginseng (KRG) is the herbal supplement that is known to be involved in a variety of pharmacological activities. We aimed to investigate the effects of KRG on neuroinflammation as a potential mechanism involved in single prolonged stress (SPS) that negatively influences memory formation and consolidation and leads to cognitive and spatial impairment by regulating BDNF signaling, synaptic proteins, and the activation of NF-kB.

METHODS: We analyzed the cognitive and spatial memory, and inflammatory cytokine levels during the SPS procedure. SPS model rats were injected intraperitoneally with 20, 50, or 100 mg/kg/day KRG for 14 days.

RESULTS: KRG administration significantly attenuated the cognitive and spatial memory deficits, as well as the inflammatory reaction in the hippocampus associated with activation of NF-κB in the hippocampus induced by SPS. Moreover, the effects of KRG were equivalent to those exerted by paroxetine. In addition, KRG improved the expression of BDNF mRNA and the synaptic protein PSD-95 in the hippocampus. Taken together, these findings demonstrate that KRG exerts memory-improving actions by regulating anti-inflammatory activities and the NF-κB and neurotrophic pathway.

CONCLUSION: Our findings suggest that KRG is a potential functional ingredient for protecting against memory deficits in mental diseases, such as PTSD.

PMID:35600771 | PMC:PMC9120622 | DOI:10.1016/j.jgr.2021.08.002

Diabetes Metab Syndr Obes. 2022 May 16;15:1527-1535. doi: 10.2147/DMSO.S365491. eCollection 2022.

ABSTRACT

BACKGROUND: The persistent coronavirus disease 2019 (COVID-19) outbreak has placed a significant burden on the scientific and medical professions. The study examined the association between body mass index (BMI), stratified by category, and severe form of COVID-19, and to explore the influence of demographic characteristics and other known risk factors.

METHODS: This was a retrospective analysis based on COVID-19 data from the Saudi Arabian Ministry of Health. Data were collected for all patients admitted to three main hospitals in Riyadh region between March 1st and July 30, 2020. The effects of BMI, demographic characteristics, clinical presentation, and comorbidities on infection severity were investigated.

RESULTS: A total of 950 patients were included in the study (70% male, 85% aged younger than 60 years old). A total of 55 (5.8%) patients were underweight, 263 (27.7%) were normal weight, 351 (37%) were overweight, 161 (17%) were obese class I, 76 (8%) were obese class II, and 44 (4.6%) were obese class III. Cough, fever, and shortness of breath were the most common symptoms among overweight patients. According to the findings of a bivariate logistic regression study, class III obesity was significantly associated with a more severe form of COVID-19 (odds ratio, 2.874; 95% confidence interval, 1.344-6.149).

CONCLUSION: This study revealed that patients with a BMI ≥40 kg/m² had a higher risk of severe COVID-19 than those with normal weight. This suggests that obesity is a risk factor for severe COVID-19 and influences disease presentation.

PMID:35600752 | PMC:PMC9121990 | DOI:10.2147/DMSO.S365491

J Ayurveda Integr Med. 2022 May 18:100587. doi: 10.1016/j.jaim.2022.100587. Online ahead of print.

ABSTRACT

BACKGROUND: Ayurveda herbal formulation AYUSH-64, proven to treat malaria and influenza-like illness in india was repurposed for COVID-19 patients considering preliminary evidances, however, scientific data was not available.

AIM: To evaluate the preliminary efficacy and safety of AYUSH 64 as an add-on to standard of care in mild COVID19 patients.

MATERIALS AND METHODS: A single centre, randomized, open-labeled, controlled, pilot study were conducted on mild COVID 19 confirmed patients. Patients allotted in interventional group (n=41) recieved AYUSH 64, 3 gm per day in three divided dose for 14 days as an adjuvant to standard of care (SOC) whereas control group received SOC (n=39) alone. Outcomes were reduction in WHO ordinal scale for clinical improvement, all-cause mortality, incidence of COVID19 symptoms among asymptomatic patients at baseline, use for oxygen therapy, use for a mechanical ventilator, the total duration of symptomatic phase and adverse events.

RESULTS: Mean score of WHO ordinal scale was reduced as time lapse in both the groups (f(1)= 20.5, p < 0.001) indicating clinical improvement among groups. There was no statistically significant difference in mean WHO ordinal scale between groups (f(1)= 0.98, p = 0.32). The proportion of asymptomatic patients progressing to the symptomatic stage is lower in AYUSH 64 group [OR, 0.68 (CI, 0.17 - 2.66)]. Mean days for the total duration of the symptomatic phase was also short in AYUSH 64 group (4.68 ± 3.29 days) compared to SOC group (5.81 ± 3.5 days). No incidence of the requirement of a mechanical ventilator, adverse drug reaction and death were observed in either of the groups.

CONCLUSION: The findings of this pilot study show that an integrated approach of AYUSH 64 with SOC provide early trends of benefit by reduction in disease progression and in total symptom duration. However, its effects remains inconclusive on outcomes such as all cause mortality, use of oxygen therapy, invasive ventilator due to sparse outcomes.

PMID:35600633 | PMC:PMC9114151 | DOI:10.1016/j.jaim.2022.100587

Ann Med Surg (Lond). 2022 May 7;78:103710. doi: 10.1016/j.amsu.2022.103710. eCollection 2022 Jun.

ABSTRACT

BACKGROUND: Long-term glucocorticoid (GC) use is the most frequent cause of adrenal insufficiency through suppression of the hypothalamic-pituitary-adrenal axis. There are no guidelines for predicting adrenal insufficiency (AI) and minimizing its risk.

METHODS: This is a prospective observational study carried out in the Endocrinology-Diabetology and Nutrition department between 2014 and 2021. All patients had received GC therapy for longer than 3 weeks before switching to hydrocortisone substitution, for various indications. These patients were admitted to our department for stimulation tests. We assessed the prevalence of AI, predicting factors, screening and management.

RESULTS: In our study the GC-induced AI was found in 49% of patients. We found a strong correlation between the basal morning serum cortisol, body mass index and the peak cortisol level after stimulation tests, while no correlation was found between adrenal function and age, sex, indication of GC therapy, duration of corticosteroid therapy, cumulative dose and daily dose. Patients with GC induced AI took a mean of 12 ± 12,18 months to recover. Adrenal function recovery rate was higher in patients tested by short Synacthen than in those tested by Insulin Hypoglycemia.

CONCLUSIONS: We demonstrated the positive correlation between serum cortisol peak levels after stimulation and body mass index. The study supports that basal cortisol level, the duration of corticoid cessation and the type of stimulation test can predict the response of cortisol to stimulation tests.

PMID:35600196 | PMC:PMC9114451 | DOI:10.1016/j.amsu.2022.103710

Ann Med Surg (Lond). 2022 May 11;78:103746. doi: 10.1016/j.amsu.2022.103746. eCollection 2022 Jun.

ABSTRACT

BACKGROUND: The current investigation aims to green synthesized the zinc nanoparticles (ZnNPs) using Lavandula angustifolia extract by microwave technique and its protoscolicidal effects alone and combined with albendazole against hydatid cyst protoscoleces.

METHODS: Different concentrations of the ZnNPs (50, 100, and 200 μg/ml) alone and combined with albendazole (ALZ, 100 μg/ml) were treated with hydatid cyst protoscoleces obtained from liver of infected sheep for 5-60 min in vitro and ex vivo. Eosin exclusion examination was used to assess the viability of protoscoleces. The induction of apoptosis in hydatid cyst protoscoleces was assessed by measurement of the Caspase-3 activity of protoscoleces treated with various concentrations of ZnNPs.

RESULTS: The size of green synthesized ZnNPs was ranged from 30 to 80 nm, most of these nanoparticles were between 50 and 60 nm in size. In vitro, the highest scolicidal effect of ZnNPs was observed at the concentration of 200 μg/ml, where it killed 81.6% of protoscolices. While the combination of these nanoparticles with ALZ, especially at the concentration of 200 μg/ml, completely killed the protoscolices after 10 min' exposure. However, compared to in vitro assay, the drugs tested took longer to show their protoscolicidal effect.

CONCLUSION: Based on the obtained results, ZnNPs particularly in combination with albendazole displayed the potent protoscolicidal in vitro and ex vivo as an intraperitoneal model of administration of agents to hydatid cyst treatment; nevertheless, additional investigations are mandatory to evaluate the efficacy and safety Zn NPs as a favorable protoscolicidal agent in clinical setting.

PMID:35600184 | PMC:PMC9118496 | DOI:10.1016/j.amsu.2022.103746

Ann Med Surg (Lond). 2022 Jun;78:103798. doi: 10.1016/j.amsu.2022.103798. Epub 2022 May 18.

ABSTRACT

Child malnourishment is a long-lasting concern that Afghanistan has been facing for many years now. This major factor amongst countless others like growing socioeconomic disparity, ineffective healthcare due to lack of funding and political instability has caused increase in nutritional instability through Afghanistan. This has increased the likelihood of numerous malnourished children contracting deadly infectious diseases like measles. Despite receiving nutritional aid, vaccines (reduce measles spread) and funding from international organizations much of these efforts have fell short due to the political instability and lack of sustained support. Emergence of COVID-19 has further intensified the already existing challenges faced by vulnerable Afghan children. The pandemic has impeded with the eradication of measles and vaccine coverage as much of the funding and attention has shifted to containing COVID-19 spread posing a greater threat for malnourished children. The combined effect of both infections has exacerbated and increased mortality in malnourished children as rate of measle spread increases. Afghan healthcare systems are now struggling more as much of their efforts are ineffectual due to lack of facilities and resources.

PMID:35600180 | PMC:PMC9113768 | DOI:10.1016/j.amsu.2022.103798

Small Sci. 2022 Mar 13:2100124. doi: 10.1002/smsc.202100124. Online ahead of print.

ABSTRACT

The current COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an enormous threat to public health. The SARS-CoV-2 3C-like protease (3CLpro), which is critical for viral replication and transcription, has been recognized as an ideal drug target. Herein, it is identified that three herbal compounds, Salvianolic acid A (SAA), (-)-Epigallocatechin gallate (EGCG), and Oridonin, directly inhibit the activity of SARS-CoV-2 3CLpro. Further, blocking SARS-CoV-2 infectivity by Oridonin is confirmed in cell-based experiments. By solving the crystal structure of 3CLpro in complex with Oridonin and comparing it to that of other ligands with 3CLpro, it is identified that Oridonin binds at the 3CLpro catalytic site by forming a C-S covalent bond, which is confirmed by mass spectrometry and kinetic study, blocking substrate binding through a nonpeptidomimetic covalent binding mode. Thus, Oridonin is a novel candidate to develop a new antiviral treatment for COVID-19.

PMID:35600064 | PMC:PMC9111243 | DOI:10.1002/smsc.202100124

Clin Case Rep. 2022 May 20;10(5):e05895. doi: 10.1002/ccr3.5895. eCollection 2022 May.

ABSTRACT

Oral dexamethasone was administered at a dose of 0.075 mg/kg/day for a boy with ataxia-telangiectasia. The SARA score was improved by 7.0 points after dexamethasone treatment over a period of 28 days. The body weight was increased by 1.4 kg after 4 weeks leading to dose titration to 0.05 mg/kg/day.

PMID:35600021 | PMC:PMC9122799 | DOI:10.1002/ccr3.5895

Front Plant Sci. 2022 May 6;13:880600. doi: 10.3389/fpls.2022.880600. eCollection 2022.

ABSTRACT

Orchid seed germination in nature is an extremely complex physiological and ecological process involving seed development and mutualistic interactions with a restricted range of compatible mycorrhizal fungi. The impact of the fungal species' partner on the orchids' transcriptomic and metabolic response is still unknown. In this study, we performed a comparative transcriptomic analysis between symbiotic and asymbiotic germination at three developmental stages based on two distinct fungi (Tulasnella sp. and Serendipita sp.) inoculated to the same host plant, Dendrobium officinale. Differentially expressed genes (DEGs) encoding important structural proteins of the host plant cell wall were identified, such as epidermis-specific secreted glycoprotein, proline-rich receptor-like protein, and leucine-rich repeat (LRR) extensin-like protein. These DEGs were significantly upregulated in the symbiotic germination stages and especially in the protocorm stage (stage 3) and seedling stage (stage 4). Differentially expressed carbohydrate-active enzymes (CAZymes) in symbiotic fungal mycelium were observed, they represented 66 out of the 266 and 99 out of the 270 CAZymes annotated in Tulasnella sp. and Serendipita sp., respectively. These genes were speculated to be involved in the reduction of plant immune response, successful colonization by fungi, or recognition of mycorrhizal fungi during symbiotic germination of orchid seed. Our study provides important data to further explore the molecular mechanism of symbiotic germination and orchid mycorrhiza and contribute to a better understanding of orchid seed biology.

PMID:35599894 | PMC:PMC9120867 | DOI:10.3389/fpls.2022.880600

Nutr Clin Pract. 2022 May 23. doi: 10.1002/ncp.10864. Online ahead of print.

ABSTRACT

We have previously advocated that nutritional care be raised to the level of a human right, in close relationship to two well-recognized fundamental rights: the right to food and the right to health. This article aims to analyze the implication of nutritional care as a human right for healthcare practitioners. We will focus on the impact of the Human Rights Basic Approach (HRBA) on healthcare professionals (HCPs), namely how they can translate HRBA into routine clinical practice. Ethics and human rights are guiding values for clinical nutrition practitioners. Together they ensure a patient-centered approach, in which the needs and rights of the patients are of the most significant importance. Human rights are based on the powerful idea of equal dignity for all people while expressing a set of core values, including fairness, respect, equality, dignity, and autonomy (FREDA). Through the analysis of FREDA principles, we have provided the elements to understand human rights and how an HRBA can support clinicians in the decision-making process. Clinical practice guidelines in clinical nutrition should incorporate disease-specific ethical issues and the HRBA. The HRBA should contribute to building conditions for HCPs to provide optimal and timely nutritional care. Nutritional care must be exercised by HCPs with due respect for several fundamental ethical values: attentiveness, responsibility competence, responsiveness, and solidarity.

PMID:35599586 | DOI:10.1002/ncp.10864

Zhonghua Wei Chang Wai Ke Za Zhi. 2022 May 25;25(5):433-439. doi: 10.3760/cma.j.cn441530-20220309-00098.

ABSTRACT

Objective: Currently, the Overlap anastomosis is one of the most favored reconstruction methods of intracorporeal esophagojejunostomy (EJS). Despite many advantages of the method, it remains some shortcomings to be improved when it comes to the retraction of the esophagus stump, the insertion of the anvil fork of the linear stapler into a "pseudo" lumen, and the closure of the common entry hole. This study aims to investigate the safety and feasibility of a multi-mode modified Overlap anastomosis. Methods: A descriptive case series study was conducted. Medical records of 152 consecutive patients who underwent totally laparoscopic total gastrectomy (TLTG) with our multi-mode modified Overlap EJS method by the same surgical team at our department from February 2017 to June 2020 were retrospectively analyzed. The multi-mode modified Overlap method mainly included (1) After ensuring the safety of tumor resection margin (proximal margin was at least 3 cm from the tumor), the esophagus was partially transected from left to right (with 5-8 mm width esophagus continuation). The specimen was then placed in a plastic bag which was tied up at the mouth using strings with a part of the esophageal wall poking through. Then the plastic bag containing the specimen was transferred to the right lumbar region, while the patient's body position was adjusted so that the abdominal esophagus could be pulled by the gravity of the specimen. (2) Using the "three-direction traction" method. The esophageal lumen was properly exposed, then guided by the gastric tube, the anvil fork was accurately placed into the esophageal lumen for completing the side-to-side EJS. (3) The 3-0 barbed suture was used in the closure of the common entry hole of the stapler from dorsally to ventrally with simple one-layer continuous suture (the stitch going from inside to inside) followed by continuous Lembert's suture (the stitch going from outside to outside). Combined with clinicopathological characteristics, the perioperative outcomes and postoperative complications of the whole group were analyzed and evaluated. Results: The study cohort included 129 men and 23 women, with a mean age of (60.2±9.1) years and a mean body mass index (BMI) of (23.2±3.1) kg/m(2). Of the 152 patients, 23 patients (15.1%) had a history of previous abdominal surgery; dentate line was invaded by tumor in 21 patients (13.8%). The mean length of the proximal resection margin was (3.3±0.3) cm and the postoperative pathological examination indicated negative resection margin tumor. The mean operative time and anastomotic time were (302.1±39.9) minutes and (29.8±5.4) minutes, respectively. The mean estimated blood loss was (87.9±46.4) ml. The mean length of postoperative hospital stay was (12.3±7.3) days. The overall severe postoperative complications (Clavien-Dindo ≥ II) occurred in 22 patients (14.5%). Six cases of pancreatic leakage were successfully recovered by adequate drainage, inhibition of pancreatic exocrine secretion and nutritional support. Ten cases of pneumonia and three cases of abdominal infection were cured with anti-infection and physical therapy. Two patients developed anastomotic leakage postoperatively. One case was caused by excessive tension of the Roux loop of the jejunum and excessive opening on the side of the jejunum after side-to-side anastomosis, and the other case was caused by an accidental intraoperative occurrence of "nasogastric tube stapled to the side-to-side anastomosis". Both of them recovered after conservative treatment including adequate drainage, anti-infection, and adequate nutritional support. One patient underwent immediate open surgery because of Peterson's hernia 7 days after TLTG, and the patient died due to extensive small bowel necrosis. Conclusions: Multi-mode modified overlap method simplifies the operation and reduces the difficulty of EJS. It is a safe and feasible method for EJS.

PMID:35599398 | DOI:10.3760/cma.j.cn441530-20220309-00098

Nephrol Ther. 2022 May 19:S1769-7255(22)00025-6. doi: 10.1016/j.nephro.2022.01.002. Online ahead of print.

ABSTRACT

INTRODUCTION: Nutrition in hemodialysis patients is important in decreasing complications, improving quality of life, and preventing of malnutrition. Recommendations of the guidelines are taken into consideration while prescribing a nutrition therapy plan for patients. However, the recommendations may differ between the guidelines. It was aimed to compare the newly published National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF KDOQI) guideline with previous reported two guideline recommendations and protein energy wasting criteria in this study.

MATERIALS AND METHODS: Fifty-five maintenance hemodialysis patients between the ages of 18-65 were included in the study. Daily energy intake and daily protein intake of these patients were evaluated by three different nutrition guidelines; NKF KDOQI-2000, 2020 and European Best Practice Guidelines-2007. In addition, protein energy wasting was determined by using anthropometric measurements, biochemical findings and food intake of the patients.

RESULTS: When the inadequacy rate in dietary daily energy intake and daily protein intake of the patients evaluated by NKF KDOQI-2000 recommendations, it was found to be higher than the rates in other two recommendations (P<0.05). Based on criteria, protein energy wasting was detected in 29.1% of the patients. While the NKF KDOQI-2020 daily energy intake recommendation was not consistent with other guideline recommendations, it seems highly compatible with protein energy wasting recommendations such as albumin, body mass index, mid-upper arm circumference, energy, and protein intake. While NKF KDOQI-2020 daily protein intake recommendation complies with European Best Practice Guidelines-2007 recommendations, the level of agreement with protein energy wasting criteria is very low.

CONCLUSION: Inadequate protein intake is still an ongoing problem in hemodialysis patients. NKF KDOQI-2020 guidelines provide a more suitable and applicable daily energy intake recommendation for patients compared to the previous guidelines.

PMID:35599164 | DOI:10.1016/j.nephro.2022.01.002

J Acad Nutr Diet. 2022 May 19:S2212-2672(22)00310-0. doi: 10.1016/j.jand.2022.04.015. Online ahead of print.

ABSTRACT

BACKGROUND: Household food insecurity persists in the United States and has important implications for health and well-being. Food insecurity in female-identified caregivers is particularly concerning given its association with their mental health and adverse health outcomes for their children. Food insecurity is associated with disordered eating, but no prior studies have examined an association between food insecurity and food addiction.

OBJECTIVE: To examine whether food insecurity is associated with higher food addiction symptom endorsement in low-income female adults.

DESIGN: Secondary analysis of baseline data from a quasi-experimental study of a mindfulness-based intervention on gestational weight gain among low-income pregnant individuals and an observational study of low-income families.

PARTICIPANTS/SETTING: Participants in Study 1 (n = 208) were English-speaking, low-income pregnant individuals with overweight or obesity, recruited in California from 2011 to 2013. Participants in Study 2 (n = 181) were English-speaking, low-income female caregivers for children between 8 and 10 years old, recruited in Michigan from 2018 to 2019. Both studies recruited participants from community health clinics, social service agencies, and online advertisements.

MAIN OUTCOME MEASURES: The primary outcome measure was food addiction symptoms, assessed by the Yale Food Addiction Scale.

STATISTICAL ANALYSIS: Multivariate Poisson regression was used to examine the association between household food insecurity and food addiction symptoms in each sample, adjusted for sociodemographic characteristics.

RESULTS: In Study 1, pregnant individuals in food-insecure households reported 21% higher food addiction symptoms than pregnant individuals in food-secure households (IRR 1.21, 95% CI 1.00, 1.47, P=.047). In Study 2, caregivers in food-insecure households had 56% higher food addiction symptoms than caregivers in food-secure households (IRR 1.56, 95% CI 1.01, 2.40, P=.045).

CONCLUSIONS: These findings provide preliminary support for a relationship between household food insecurity and food addiction. Future research should examine potential mechanisms and whether interventions to reduce food insecurity lower risk of food addiction.

PMID:35598730 | DOI:10.1016/j.jand.2022.04.015

Cancer Immunol Immunother. 2022 May 22. doi: 10.1007/s00262-022-03213-5. Online ahead of print.

ABSTRACT

Bacterial flora has clinical significance for the host. The metabolic environment created by this flora influences immunotherapy in urothelial carcinoma. However, there are no reports on the clinical significance of bacterial flora in the host bloodstream. We aimed to clarify the correlation between extracellular vesicle (EV)-derived blood microflora information and tumor immunological status in urothelial carcinoma (UC) patients. Serum samples were collected from 20 healthy donors, 50 patients with localized UC, and 31 patients with metastatic UC (mUC) who had undergone pembrolizumab treatment. Bacterial DNA in EVs was extracted from each sample. Metagenomic sequencing was performed after amplification of the V1-V2 region of the bacterial 16S rRNA gene. Using the matched tumor tissue and serum samples, we revealed that the smaller amount of peripheral EVs carrying Firmicutes DNA was significantly correlated with the higher number of infiltrating T cells within tumor tissues (CD3; p = 0.015, CD4; p = 0.039, CD8; p = 0.0084) and the higher expression of activation markers on their surface (ICOS on both CD4; p = 0.0013 and CD8 T cells; p = 0.016 and 4-1BB on CD4 T cells; p = 0.016). In terms of circulating metabolic information, L-Ser and L-Pro levels, which play important roles in T cell expansion and proliferation, were significantly higher in the Firmicutes-low group (p = 0.010). All of the patients with higher Firmicutes abundance had disease progression without any clinical response (p = 0.026) and significantly inferior prognosis for pembrolizumab therapy (p = 0.035). This is the first study on the importance of peripheral bacterial EVs in cancer patients treated with cancer immunotherapy.

PMID:35598195 | DOI:10.1007/s00262-022-03213-5

Virol J. 2022 May 21;19(1):87. doi: 10.1186/s12985-022-01808-z.

ABSTRACT

BACKGROUND: The new coronavirus (COVID-19) has been transmitted exponentially. Numerous studies have been performed in recent years that have shown the inhibitory effect of plant extracts or plant-derived compounds on the coronavirus family. In this study, we want to use systematic review and meta-analysis to answer the question, which herbal compound has been more effective?

MAIN BODY: The present study is based on the guidelines for conducting meta-analyzes. An extensive search was conducted in the electronic database, and based on the inclusion and exclusion criteria, articles were selected and data screening was done. Quality control of articles was performed. Data analysis was carried out in STATA software.

CONCLUSION: Due to the variety of study methods, definitive conclusions are not possible. However, in this study, we attempted to gather all the available evidence on the effect of plant compounds on SARS-COV-2 to be used for the development and use of promising antiviral agents against this virus and other coronaviruses. Trypthantrin, Sambucus extract, S. cusia extract, Boceprevir and Indigole B, dioica agglutinin urtica had a good effect on reducing the virus titer. Also among the compounds that had the greatest effect on virus inhibition, Saikosaponins B2, SaikosaponinsD, SaikosaponinsA and Phillyrin, had an acceptable selectivity index greater than 10. Andrographolide showed the highest selectivity index on SARS-COV-2. Our study confirmed insufficient data to support alkaloid compounds against SARS-COV-2, and the small number of studies that used alkaloid compounds was a limitation. It is recommended to investigate the effect of more alkaloid compounds against Corona virus.

PMID:35597998 | DOI:10.1186/s12985-022-01808-z

Methods. 2022 May 18:S1046-2023(22)00117-7. doi: 10.1016/j.ymeth.2022.05.003. Online ahead of print.

ABSTRACT

Chinese herbal formulae are the heritage of traditional Chinese medicine (TCM) in treating diseases through thousands of years. The formula function is not just a simple herbal efficacy addition, but produces complex and nonlinear relationships between different herbs and their overall efficacy, which brings challenges to the formula efficacy analysis. In our study, we proposed a model called HPE-GCN that combines graph convolutional networks (GCN) with TCM-defined herbal properties (TCM-HPs) to predict formulae efficacy. In addition, to process the unstructured natural language in the formula text, we proposed a weighting calculation method related to herb frequency and the number of herbs in a formula called Formula-Herb dependence degree (FHDD), to assess the dependency degree of a formula with its herbs. In our research, 214 classic tonic formulae from ancient TCM books such as Synopsis of the Golden Chamber, Jingyue's Complete Works and the Golden Mirror of Medicin were collected as datasets. The performance of HPE-GCN on multi-classification of tonic formulae reached the best result compared with classic machine learning models, such as support vector machine, naive Bayes, logistic regression, gradient boosting decision tree, and K-nearest neighbors. The evaluated index Macro-Precision, Macro-Recall, Macro-F1 of HPE-GCN on the test set were 87.70%, 84.08% and 83.51% respectively, increased by 7.27%, 7.41% and 7.30% respectively from second best compared models. GCN has the advantage of low-dimensional feature expression for herbs and formulae, and is an effective analysis tool for TCM research. HPE-GCN integrates TCM-HPs and fits the complex nonlinear mapping relationship between TCM-HPs and formulae efficacy, which provides new ideas for related research.

PMID:35597515 | DOI:10.1016/j.ymeth.2022.05.003

J Ethnopharmacol. 2022 May 18:115334. doi: 10.1016/j.jep.2022.115334. Online ahead of print.

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Wound healing is a complex process that can leave pathological scars, especially in case of infections from opportunistic microorganisms. In this context, herbal medicines open up great possibilities for investigation. One of the species of interest native to Brazil is Garcinia brasiliensis ("bacupari"). Traditionally known for treating wounds and ulcers, G. brasiliensis presents anti-inflammatory, antioxidant and antimicrobials properties. But, its wound healing profile in experimental models, in order to validate its efficacy, is still litle studied.

AIM OF THE STUDY: Thus, the objective of this work was to evaluate, in an infected cutanous wound model, the potential of formulations incorporated with G. brasiliensis leaves extracts.

MATERIALS AND METHODS: Crude extract (CE), Ethyl Acetate Fraction (EAF) and Hexanic Fraction (HF) were submitted to phytochemical assays, high performance thin layer chromatography (HTPLC) and cytotoxicity studies. CE and EAF were also tested for microbicidal properties and incorporated in cream and gel formulations at 10% concentration. After stability testing, the gel formulations with CE or EAF at 10% were selected and applied to skin wounds infected or not with Staphylococcus aureus in Wistar rats. The healing potenttial of the extracts was verified by the expression of the protein Annexin A1 (AnxA1), related to the processes of inflammation and antifibrotic function, the cells immunostaining for Gasdermin-D (GSDM-D), a marker of pyroptotic cell death, and the dosage of interleukin-10 (IL-10) and monocyte chemotactic protein (MCP)-1 inflammatory mediators.

RESULTS: Phytochemical studies indicated the presence of compounds of pharmacological interest, including Catechin, Quercetin and Berberine in addition to low cytotoxicity of CE and EAF at 10%. After the 6-day topical treatments, CE and EAF gel formulations demonstrated to control the pruritus formation process. The treatments decreased AnxA1 expression and the amount of cells immunostained for GSDM-D, and increased the expression of MCP-1 in infected wounds.

CONCLUSIONS: Together, the results show important anti-inflammatory profile and skin healing potential of CE and EAF from G. brasiliensis leaves, even in infected lesions, with therapeutic perspectives.

PMID:35597412 | DOI:10.1016/j.jep.2022.115334

J Ethnopharmacol. 2022 May 18:115395. doi: 10.1016/j.jep.2022.115395. Online ahead of print.

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Zuojin Pill, a traditional poly-herbal drug, comprises Coptis chinensis Franch - Tetradium ruticarpum (A. Juss.) T.G. Hartley (6:1). The significant quantity of alkaloids found in the participating herbs is a key aspect of the Zuojin Pill. According to traditional Chinese medicine (TCM), these numerous alkaloidal compounds within Zuojin Pill have various essential therapeutic effects.

AIM OF THE STUDY: The alkaloids in Tetradium are mainly indole alkaloids, while the alkaloids in Coptis are mostly isoquinoline alkaloids with low bioavailability. Alkaloids and their metabolites are nitrogen-containing compounds or weakly alkaline substances that can be partially ionized under physiological pH conditions. Fortunately, organic cation transporters (OCTs) play a crucial role in the cellular uptake of weakly alkaline compounds. Therefore, we speculated that the alkaloidal compounds might interact with liver cation transporters hOCT1 and kidney cation transporters hOCT2 to alter cell drug disposal. In order to clarify our hypothesis, a series of alkaloids-OCTs interaction experiments were conducted.

MATERIALS AND METHODS: HEK293 cells stably expressing hOCT1 and hOCT2 were modeled and evaluated. Afterward, high-content screening (HCS) was conducted to analyze whether the main alkaloids and their metabolites of Coptis - Tetradium were inhibitors of hOCT1 and hOCT2 transporters. Meanwhile, LC-MS/MS was used to investigate whether the alkaloidal compounds were substrates of hOCT1 and hOCT2 transporters. Finally, drug interactions at the cellular level were assessed by LC-MS/MS after co-administration of berberine and rutacorine.

RESULTS: Berberine, jateorhizine, coptisine, epiberberine, columbamine, demethyleneberberine, and berberrubine could significantly inhibit hOCT1 and hOCT2 activity. Isoquinoline alkaloids, including berberine, jateorhizine, coptisine, epiberberine, columbamine, and palmatine, were substrates of hOCT1 and hOCT2, but not the indole alkaloids evodiamine and rutaecarpine. Furthermore, evodiamine at a concentration of 20 μmol/L had a trivial effect on berberine accumulation in HEK293-hOCT2 cells.

CONCLUSIONS: These results support the idea that alkaloidal compounds within Coptis and Tetradium have hOCT1 and hOCT2 inhibitory activity or be their substrates, and the increased oral bioavailability of berberine in vivo was closely related to the potential interactions of small molecules in Coptis- Tetradium. Overall, our study provides a framework for investigating the potential interactions of small molecules in Coptis- Tetradium.

PMID:35597409 | DOI:10.1016/j.jep.2022.115395

Biomed Pharmacother. 2022 May 17;151:113100. doi: 10.1016/j.biopha.2022.113100. Online ahead of print.

ABSTRACT

Chronic distress-induced hypothalamic-pituitary-adrenal axis deregulations have been associated with the development of neuropsychiatric disorders such as anxiety and depression. Currently available drugs treating such pathological conditions have limited efficacy and diverse side effects, revealing the need of new safer strategies. Aromatic plant-based compounds are largely used in herbal medicine due to their therapeutic properties on mood, physiology, and general well-being. The purpose of this study was to investigate the effects of 2-phenylethyl alcohol (PEA), one of the pharmacologically active constituents of rose essential oil, on chronic corticosterone (CORT)-induced behavioral and neurobiological changes in female mice. Animals followed a prolonged PEA inhalation exposure (30 min per day) for 15 consecutive days prior to behavioral evaluation with open-field, forced swim and novelty-suppressed feeding tests. CORT treatment induced an anxio-depressive-like phenotype, evidenced by a reduced locomotor activity in the open-field, and an increased latency to feed in the novelty-suppressed feeding paradigms. To elucidate the neural correlates of our behavioral results, immunohistochemistry was further performed to provide a global map of neural activity based on cerebral cFos expression. The altered feeding behavior was accompanied by a significant decrease in the number of cFos-positive cells in the olfactory bulb, and altered functional brain connectivity as shown by cross-correlation-based network analysis. CORT-induced behavioral and neurobiological alterations were reversed by prolonged PEA inhalation, suggesting a therapeutic action that allows regulating the activity of neural circuits involved in sensory, emotional and feeding behaviors. These findings might contribute to better understand the therapeutic potential of PEA on anxio-depressive symptoms.

PMID:35597115 | DOI:10.1016/j.biopha.2022.113100

Phytomedicine. 2022 May 10;102:154163. doi: 10.1016/j.phymed.2022.154163. Online ahead of print.

ABSTRACT

BACKGROUND: Artemisia anomala S. Moore (Compositae), known as "Nan-Liu-Ji-Nu" in traditional Chinese medicine (TCM), has been used to treat many inflammatory diseases, including enteritis, acute icteric hepatitis, rheumatism, toothache, tonsillitis, and chronic bronchitis, for centuries. Our preliminary studies have demonstrated that the ethanolic extract of A. anomala (EAA) might be with the potential of inhibiting the activation of the NLRP3 inflammasome. However, the anti-inflammatory activity of EAA based on NLRP3 inflammasome inhibition is still unclear.

PURPOSE: This work aimed to elucidate the anti-inflammatory mechanism of EAA by inhibiting NLRP3 inflammasome activation.

METHODS: Lipopolysaccharide (LPS)-primed bone marrow-derived macrophages (BMDMs) were used to evaluate the inhibitory effects on NLRP3 inflammasome activation. The level of IL-1β was determined by ELISA. The expression levels of IL-1β, caspase-1, NLRP3, and ASC were assayed using western blot analysis. ASC oligomerization and speck formation were detected by immunofluorescence microscopy. The measurements of intracellular chloride and potassium were conducted using N-(ethoxycarbonylmethyl)-6-methoxyquinolinium bromide (MQAE) probe assay and inductively coupled plasma-optical emission spectrometry (ICP-OES), respectively. Mitochondrial reactive oxygen species (mtROS) were examined using the MitoSOX method. Acridine orange (AO) staining was used to detect the permeability of the lysosomal membrane. A DSS-induced ulcerative colitis model was established to evaluate the anti-inflammatory effects of EAA in vivo. Finally, high-performance liquid chromatography (HPLC) was employed to identify and quantify the major constituents of EAA.

RESULTS: In BMDMs, EAA significantly inhibited the release of IL-1β induced by LPS. The mechanistic study revealed that EAA inhibited NLRP3 inflammasome activation by blocking the oligomerization of ASC and suppressed the LPS-induced priming step. Furthermore, EAA protected lysosomes by inhibiting the TAK1-JNK pathway, thereby inhibiting the assembly of downstream NLRP3 inflammasome and the production of IL-1β. In addition, EAA exerted potent protective effects in an ulcerative colitis model by decreasing the content of colonic IL-1β and alleviating the process of ulcerative colitis. HPLC analysis identified eight main components of EAA, including isofraxidin (1), quercetin-7-O-β-D-glucopyranoside (2), apigenin-7-O-β-D-glucopyranoside (3), 7-methoxycoumarin (4), quercetin (5), luteolin (6), kaempferol (7), and eupatorin (8), Of these compounds, quercetin and kaempferol were found to be the most potent ingredients.

CONCLUSION: These findings collectively reveal that EAA exerts anti-inflammatory effects by both suppressing the NLRP3 priming step and protecting lysosomes to inhibit NLRP3 inflammasome activation, suggesting that this traditional herbal medicine might be used to treat NLRP3-driven inflammatory diseases.

PMID:35597027 | DOI:10.1016/j.phymed.2022.154163

Vopr Pitan. 2022;91(2):58-71. doi: 10.33029/0042-8833-2022-91-2-58-71. Epub 2022 Mar 14.

ABSTRACT

Insufficient vitamin content in the diet is a risk factor for the development of various diseases and their progression, and drug therapy can also contribute to the development of a deficiency of these micronutrients. Data on vitamin sufficiency of patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN) are needed to develop measures to improve it. The aim of the research was to compare vitamin status of patients with T2DM without DN and those with T2DM complicated by nephropathy by assessing vitamin blood level and urinary excretion. Material and methods. In a single-stage research, 57 patients with T2DM and concomitant obesity (14 men, 43 women aged 42-75 years) have been examined. The 1st group included 26 patients with T2DM (7 men and 19 women, BMI 41.5±1.7 kg/m²) with glycated hemoglobin (HbA1c) - 8.0±1.4%, blood serum glucose level 8.1±0.6 mmol/l, glomerular filtration rate (GFR) - 86.7±3.0 ml/min per 1.73 m², microalbuminuria - 18.0±2.0 mg/day. The 2nd group included 31 patients with T2DM complicated by DN (7 men and 24 women, BMI 42.5±1.3 kg/m²), with an HbA1c level of 6.4±0.2%, blood serum glucose level 6.8±0.3 mmol/l, GFR - 62.8±2.7 ml/min per 1.73 m², microalbuminuria - 59.5±22.5 mg/day. The determination of vitamins С (ascorbic acid), A (retinol), E (α- and γ-tocopherols), D [25(OH)D], B₂ (riboflavin) and β-carotene in blood serum and vitamins C (ascorbic acid), B₁ (thiamine), B₂ (riboflavin) and B₆ (4-pyridoxic acid) in the morning portion of urine collected on an empty stomach within 40-120 min was carried out. The vitamin status was assessed based on the concentration of vitamins in blood serum and urinary excretion relative to the lower limit of the norm, as well as using the criteria for the optimal supply and 2 molar ratios. Results. Compared to patients with T2DM without nephropathy, patients with DN were better provided with vitamins B₂, A and β-carotene: vitamin B₂ deficiency was found 3.2 fold less often (in 9.7%), β-carotene - 1.8 fold less often (in 35.5%), nonoptimal retinol level occurred twice less often (in 41.9%). At the same time, serum α-tocopherol level below the optimal level was found in 67.7% of individuals versus 50% among patients with T2DM without nephropathy, with a significantly reduced urinary excretion of vitamins B₁ and B₂. With the exception of one man, the rest of the DN patients had a deficiency or lack of vitamin D. The characteristic features of the vitamin status of patients in both groups were the complete absence of individuals who were simultaneously optimally provided with all the studied vitamins and β-carotene (when assessing the vitamin status using both the absolute serum vitamer levels and 2 additional molar ratios), and a high frequency of detection of several simultaneously non-optimal vitamin status indicators. A negative correlation was found between blood serum level of β-carotene and glycemia (ρ=-0.359, p=0.006), as well as GFR (ρ=-0.289, р=0.029) and positive with high-density lipoprotein cholesterol (ρ=0.423, р=0.001), that indicated the need to increase this antioxidant blood level in patients with T2DM. The presence of a negative correlation between the concentration ratio of vitamins C and E and glucosuria (ρ=-0.288, p=0.033) and postprandial glycemia (ρ=-0.313, p=0.031) indicated the need to maintain it at an optimal level. Conclusion. For patients with T2DM and concomitant obesity, vitamin D and β-carotene turned out to be the most problematic, since their reduced levels are detected more often than other vitamins. In addition to the optimal blood level of vitamins C and E, it is extremely important for them to maintain the blood molar ratio of ascorbic acid and α-tocopherol at an optimal level. The purposefully development of specialized vitamin complexes containing effective doses is necessary for patients with DN.

PMID:35596636 | DOI:10.33029/0042-8833-2022-91-2-58-71

Vopr Pitan. 2022;91(2):21-30. doi: 10.33029/0042-8833-2022-91-2-21-30. Epub 2022 Mar 14.

ABSTRACT

There are no clear dietary recommendations for patients over 70 years of age, while stages 3-5 of chronic kidney disease (CKD) and protein-energy wasting (PEW) is common among this category of patients. Nutritional status is known to be one of the significant factors influencing the prognosis of patients receiving renal replacement therapy. The aim of the research was the analysis of the mechanisms of PEW, methods for assessing the nutritional status and effectiveness of diets with different protein content in patients with CKD based on literature data. Material and methods. The research material was the scientific literature presented in the domestic and international (eLIBRARY, PubMed, Google Scholar) databases, as well as clinical recommendations for the management of geriatric patients with CKD, dietary recommendations for patients with anorexia and other conditions. Results. The studies devoted to the mechanisms of PEW were analyzed. One of the leading causes of this condition is anorexia, in the pathogenesis of which uremic toxins, inflammation and hormonal disorders are involved (hormones such as gastrin, cholecystokinin, leptin, insulin, testosterone and others may be involved in the pathogenesis). A number of studies have shown that limiting protein to 0.6 g/kg day could significantly reduce uremic dyspepsia risk and slow CKD progression. At the same time, several researchers gave data on the ineffectiveness of a low-protein diet in patients with CKD and diabetes mellitus and a significant risk of malnutrition. Subjective global assessment, the mini nutrition assessment and the geriatric nutritional risk index can be distinguished among the methods of assessing nutritional status. Conclusion. Research data on the effectiveness of a low-protein diet in elderly patients with stage 3B-5 CKD are contradictory. PEW in CKD is common and largely determines survival; the mechanism of PEW is complex. The study of the optimal nutritional diet for elderly patients with predialysis stages of CKD still remains an urgent problem.

PMID:35596632 | DOI:10.33029/0042-8833-2022-91-2-21-30

Vopr Pitan. 2022;91(2):5-14. doi: 10.33029/0042-8833-2022-91-2-5-14. Epub 2022 Mar 14.

ABSTRACT

The TCF7L2 gene is one of the new markers associated with the development of type 2 diabetes mellitus (DM). Evaluation of the effect of TCF7L2 gene polymorphisms on the effectiveness of hypoglycemic therapy will allow an individual approach to the choice of methods for treating type 2 DM in their carriers. The aim of the research was to study the effect of carriage of TCF7L2 gene polymorphisms on glycemic control parameters in patients with type 2 DM receiving metformin glucose-lowering therapy in combination with a low-calorie version of the standard diet. Material and methods. The study included 55 patients with type 2 DM (mean age 59.9±6.9, BMI 44.3±8.2 kg/m²) receiving metformin monotherapy at a dosage of 1500-2000 mg/day in combination with a low-calorie variant of the standard diet (1730±130 kcal/day). The frequency of occurrence of polymorphisms rs7903146/rs12255372 of the TCF7L2 gene was studied. The indicators of glycemic and metabolic control, anthropometric parameters and body composition were evaluated. Results. The frequency of occurrence of the T-allele of both single nucleotide polymorphisms rs7903146 and rs12255372 of the TCF7L2 gene among patients was 38.2%. Among carriers of the T-allele rs7903146 of the TCF7L2 gene, 72% of patients responded to therapy, showing a statistically significant decrease in the level of fasting glycemia by an average of 16.2±1.6% from the baseline, while among carriers of the CC genotype - 10.5±1.5% (p=0.017). There were no statistically significant changes in glycemic control indicators on hypoglycemic therapy during 7 months of observation, both in the group of T allele and CC genotype carriers. Conclusionss. An improvement in glycemic control was established in patients with type 2 DM among carriers of the T allele rs7903146 of the TCF7L2 gene during metformin therapy in combination with a low-calorie standard diet. The study of TCF7L2 gene polymorphism in combination with indicators of glucose metabolism makes it possible to predict the effectiveness of hypoglycemic therapy with great accuracy.

PMID:35596630 | DOI:10.33029/0042-8833-2022-91-2-5-14

Hepatol Commun. 2022 May 21. doi: 10.1002/hep4.1959. Online ahead of print.

ABSTRACT

Nitrofurantoin, minocycline, methyldopa and infliximab, have been found to induce autoimmune-like hepatitis (DI-AILH). Evidence for other drugs and herbal and dietary supplements (HDS) is unclear. The aims of the study were to establish criteria to define and review the published evidence of suspected DI-AILH. Search was undertaken in Pubmed using search terms "drug-induced liver injury," "autoimmune hepatitis," and "drug-induced autoimmune hepatitis." DI-AILH was defined as (1) drug as a potential trigger of liver injury with autoimmune features and histological findings compatible with AIH; (2) no or incomplete recovery or worsening of liver tests after discontinuation of the drug; (3) corticosteroids requirement or spontaneous recovery; (4) follow-up without immunosuppression (IS) and no relapse of AIH at least 6 months after discontinuation of IS; and (5) drugs potentially inducing AILH with a chronic course. Cases fulfilling the first four criteria were considered probable DI-AILH with three possible DI-AILH. A total of 186 case reports were identified for conventional drugs (n = 148; females 79%; latency 2.6 months) and HDS (n = 38; females 50%). The most commonly reported agents of DI-AILH were interferons (n = 37), statins (n = 24), methylprednisolone (MPS) (n = 16), adalimumab (n = 10), imatinib (n = 8), and diclofenac (n = 7). Tinospora cordifolia and Khat were the only HDS with probable DI-AILH cases. No relapses of AIH were observed when IS was stopped after interferons, imatinib, diclofenac, and methylprednisolone. Conclusion: Beyond well-recognized nitrofurantoin, methyldopa, hydralazine, minocycline, and infliximab as causes of DI-AILH, interferons, imatinib, adalimumab, and MPS were the best-documented agents leading to probable DI-AILH. Khat and Tinospora cordifolia were the only HDS found to be able to induce DI-AILH. Long-term immunosuppression appears to be rarely required in patients with DI-AILH due to these drugs.

PMID:35596597 | DOI:10.1002/hep4.1959

Inquiry. 2022 Jan-Dec;59:469580221102202. doi: 10.1177/00469580221102202.

ABSTRACT

Background and Aim: Alternative treatments for respiratory disorders attempt to prevent or relieve symptoms and enhance functions. Furthermore, substantial evidence shows that several herbal medicines have been clinically effective against respiratory disorders. Thus this study assesses the Saudi students' use, beliefs, and practices related to herbal and dietary supplements for the possible prevention of respiratory infections. Methods: A cross-sectional web-based survey was designed using Google Forms to collect the data from the healthcare and non-healthcare students currently pursuing their courses at King Saud University, Riyadh, Saudi Arabia. The data was collected over 4 months, from November 2021 to February 2022, using convenience sampling with a 25-item questionnaire. A statistical package for social sciences, SPSS 26, was used to analyze the data. Results: A total of 274 participants responded to the study. The mean age of the respondents was 21.9 ± 3.08 (mean (SD)). The prevalence of herbal medicine (HM) was found to be 62.7% (n = 172). Around 48.5% (n = 133) of the respondents occasionally used some form of HM during the period of an illness associated with a respiratory infection. About 66% of the respondents agreed that using HMs prevents or controls respiratory symptoms and strengthens immunity. A majority (75.2%) of the respondents agreed that ginger extract possesses antiviral and immunity-boosting properties, followed by garlic extract (59.5%), cinnamon (39.4%), and lemongrass (38.3%). In addition, between 37% and 45.6% of the respondents agreed that vitamin C and vitamin D intake helps in boosting immunity and reducing the likelihood of developing respiratory infections. The overall mean of the positive beliefs and practice score was 9.6 (range 0-14). The mean positive beliefs and practice scores were significantly higher for males (11.4 ± 3.2) compared to females (8.6 ± 3.6) (P < .001). The numbers were not significantly different regardless of the source of information (9.6 ± 3.5), respondents being in health colleges (8.9 ± 4.1) or non-health colleges (9.8 ± 3.7), them being previously or currently infected (9.7 ± 3.8), the absence of infection (9.7 ± 3.8), or the respondents possessing a history of chronic diseases (10.5 ± 3.9) or not (9.5 ± 3.7) (P > .05). Conclusions: This study found a relatively high prevalence of herbal and dietary supplements' use, positive beliefs, and practices to strengthen one's immunity against respiratory symptoms.

PMID:35596542 | DOI:10.1177/00469580221102202

BMC Pregnancy Childbirth. 2022 May 20;22(1):425. doi: 10.1186/s12884-022-04753-5.

ABSTRACT

BACKGROUND: Mothers in rural Ethiopian communities prefer giving birth at home. In developing countries, traditional birth attendants play an important role in reducing the maternal mortality rate. In Ethiopia, however, their role during pregnancy, childbirth, the postnatal period, and their integration with health professionals is not clearly defined. This study aimed to explore the role of traditional birth attendants in feto-maternal care during pregnancy, childbirth, and the postnatal period, and integration with health professionals in the West Omo Zone, southern Ethiopia.

METHODS: A qualitative descriptive design was used with triangulation of methods and data sources. We conducted in-depth interviews with traditional birth attendants, key informant interviews with health care professionals and community or religious leaders, and two focus group discussions with multiparous pregnant women. Each interview and focus group discussion was tape-recorded and the data obtained were transcribed and translated into English for analysis. The analysis was done based on thematic analysis framework.

RESULTS: Traditional birth attendants stated that they used herbal remedies to treat nausea and vomiting, decrease pain during labor, and increase pregnant women's desire to push. The absence of incentives for their work, shortage of logistics, and lack of training was mentioned as challenges to the continuity of their roles. All study participants explained the importance of training traditional birth attendants on maternal and child health in rural communities. However, health care professionals reported that few traditional birth attendants advised mothers about traditional practices such as milk tooth extraction and uvulectomy.

CONCLUSION AND RECOMMENDATION: Traditional birth attendants continued their roles despite the existing challenges. There was no integration between TBA and the formal health care system. The need for training traditional birth attendants has been emphasized by all study participants and its impact on reducing feto-maternal death was recognized by health care professionals. Therefore, the federal ministry of health should works better for the development of TBAs to scale up their skills across all regions in the country.

PMID:35596165 | PMC:PMC9123652 | DOI:10.1186/s12884-022-04753-5

Z Rheumatol. 2022 May 20. doi: 10.1007/s00393-022-01218-0. Online ahead of print.

ABSTRACT

Gout is the most common inflammatory arthritis in men with a rising incidence worldwide. It is a metabolic disease caused by hyperuricemia. Common causes of hyperuricemia, in addition to hereditary reduced renal excretion of urate, include purine over-nutrition, aging, comorbidities and associated medications, some of which increase serum urate levels. The first gout flare represents the signal for deposited urate crystals. If hyperuricemia remains untreated, crystal deposition proceeds and can cause recurrent gout flares, joint destruction and tophi. There is evidence that silent inflammation is ongoing even during asymptomatic stages. Gout patients often exhibit other metabolic, renal and cardiovascular co-morbidities and have higher (cardiovascular) mortality. Therefore, guidelines call for consequent urate lowering strategies to bring serum urate levels to a target at least below 360 µmol/l. The following article summarizes the recent state of knowledge regarding the diagnosis and therapy of gout.

PMID:35596003 | DOI:10.1007/s00393-022-01218-0

Endocrinol Diabetes Nutr (Engl Ed). 2022 May 17:S2530-0180(22)00047-6. doi: 10.1016/j.endien.2021.03.003. Online ahead of print.

ABSTRACT

INTRODUCTION: Resident physicians' proper use of nutritional support and knowledge about Clinical Nutrition is essential to ensuring that their patients receive suitable nutritional care.

MATERIALS AND METHOD: An online survey was sent to resident physicians at our hospital in specialisations with hospital beds. The survey featured 20 multiple-choice questions scored from 1 to 10 (1 being "completely disagree" and 10 being "completely agree") across the following themes: nutritional assessment, diets, oral nutritional supplements, enteral nutrition and perception of the Nutrition Unit.

RESULTS: The survey was completed by 69% of resident physicians in medical specialisations and 70% of those in surgical specialisations. Overall, the average survey score was 6.28, with higher scores among medical residents than surgical residents (6.86 versus 5.38; p < 0.001), especially in the sections on nutritional assessment, diets and oral nutritional supplements. The respondents had a positive perception of the Nutrition Unit (mean score 7.6).

DISCUSSION: Residents in medical specialisations afford greater importance to their patients' nutrition than residents in surgical specialisations, although in both groups the average score was rather low. There is much room for improvement in the training in Clinical Nutrition of this group, and it is important to include topics in Clinical Nutrition in training programmes for all residents in hospital specialisations.

PMID:35595656 | DOI:10.1016/j.endien.2021.03.003