Calcium levomefolate 15mg gastro-resistant tablets

ObjectivesTo examine the strengths and limitations of existing data to provide guidance for the use of folate supplements as treatment, with or without other psychotropic medications, in various psychiatric disorders. To identify area for further research in terms of the biosynthesis of mechanism of folate and genetic variants in metabolic pathway in human.MethodsA systematic review of published literature following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, to assess whether folate supplements are beneficial in certain psychiatric disorders (depression, bipolar disorder, schizophrenia, autism spectrum disorder, and attention deficit hyperactivity disorder). Methodology of this review is registered with Prospero (Registration number CRD 42021266605).Data sourcesEligible studies were identified using a systematic search of four electronic databases: Embase, Pubmed, PsycINFO, and Cochrane. The search strategy covered the time period from 1974 to August 16th, 2021. Therefore, this review examines randomized control trials or open-label trials completed during this period.ResultsWe identified 23 studies of folate supplements in various psychiatric disorders for critical review. Of these, 9 studies investigated the efficacy of folate supplements in major depressive disorders, 5 studies in schizophrenia, 6 studies in autism spectrum disorder, 2 studies in bipolar affective disorder and 1 study in attention deficit hyperactive disorder. The most consistent finding association of oral levomefolic acid or 5-methylfolate with improvement in clinical outcomes in mental health conditions as mentioned above, especially in major depressive disorder (including postpartum and post-menopausal depression), schizophrenia, autism spectrum disorder, attention deficit hyperactivity disorder and bipolar affective disorder. Folate supplements were well tolerated.LimitationOur results are not representative of all types of studies such as case reports or case series studies, nor are they representative of the studies conducted in languages that are not in English or not translated in English.ConclusionIncreasing evidence from clinical trials consistently demonstrate folate supplements, especially levomefolic acid or 5-methylfolate, may improve clinical outcomes for certain psychiatric diseases, especially as an adjunct pharmacotherapy with minimal side effects.

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Schizophrenia is a disease with a complex etiology that significantly impairs the functioning of patients. In recent years, there has been increasing focus on the importance of the gut microbiota in the context of the gut-brain axis. In our study, we analyzed data on the gut-brain axis in relation to schizophrenia, as well as the impacts of eating habits, the use of various supplements, and diets on schizophrenia. Additionally, the study investigated the impact of antipsychotics on the development of metabolic disorders, such as diabetes, dyslipidemia, and obesity. There may be significant clinical benefits to be gained from therapies supported by supplements such as omega-3 fatty acids, B vitamins, and probiotics. The results suggest the need for a holistic approach to the treatment of schizophrenia, incorporating both drug therapy and dietary interventions.

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The pandemic of novel coronavirus disease 2019 (COVID-19) has rampaged the world, with more than 58.4 million confirmed cases and over 1.38 million deaths across the world by 23 November 2020. There is an urgent need to identify effective drugs and vaccines to fight against the virus. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) belongs to the family of coronaviruses consisting of four structural and 16 non-structural proteins (NSP). Three non-structural proteins, main protease (Mpro), papain-like protease (PLpro), and RNA-dependent RNA polymerase (RdRp), are believed to have a crucial role in replication of the virus. We applied computational ligand-receptor binding modeling and performed comprehensive virtual screening on FDA-approved drugs against these three SARS-CoV-2 proteins using AutoDock Vina, Glide, and rDock. Our computational studies identified six novel ligands as potential inhibitors against SARS-CoV-2, including antiemetics rolapitant and ondansetron for Mpro; labetalol and levomefolic acid for PLpro; and leucal and antifungal natamycin for RdRp. Molecular dynamics simulation confirmed the stability of the ligand-protein complexes. The results of our analysis with some other suggested drugs indicated that chloroquine and hydroxychloroquine had high binding energy (low inhibitory effect) with all three proteins-Mpro, PLpro, and RdRp. In summary, our computational molecular docking approach and virtual screening identified some promising candidate SARS-CoV-2 inhibitors that may be considered for further clinical studies.

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Major Depressive Disorder (MDD) is a highly prevalent psychiatric disorder worldwide. It causes individual suffering, loss of productivity, increased health care costs and high suicide risk. Current pharmacologic interventions fail to produce at least partial response to approximately one third of these patients, and remission is obtained in approximately 30% of patients. This is known as Treatment-Resistant Depression (TRD). The burden of TRD exponentially increases the longer it persists, with a higher risk of impaired functional and social functioning, vast losses in quality of life and significant risk of somatic morbidity and suicidality. Different approaches have been suggested and utilized, but the results have not been encouraging. In this review article, we present new approaches to identify and correct potential causes of TRD, thereby reducing its prevalence and with it the overall burden of this disease entity. We will address potential contributory factors to TRD, most of which can be investigated in many laboratories as routine tests. We discuss endocrinological aberrations, notably, hypothalamic-pituitary-adrenal (HPA) axis dysregulation and thyroid and gonadal dysfunction. We address the role of Vitamin D in contributing to depression. Pharmacogenomic testing is being increasingly used to determine Single Nucleotide Polymorphisms in Cytochrome P450, Serotonin Transporter, COMT, folic acid conversion (MTHFR). As the role of immune system dysregulation is being recognized as potentially a major contributory factor to TRD, the measurement of C-reactive protein (CRP) and select immune biomarkers, where testing is available, can guide combination treatments with anti-inflammatory agents (e.g., selective COX-2 inhibitors) reversing treatment resistance. We focus on established and emerging test procedures, potential biomarkers and non-biologic assessments and interventions to apply personalized medicine to effectively manage treatment resistance in general and TRD specifically.

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Drought is the most significant abiotic stress that impedes agroforestry development. In nature, drought tolerance also depends on the ability to compensate after water restoration. Dark septate endophytes (DSEs) are believed to enhance plant tolerance in drought environments. However, the compensatory mechanisms of DSEs for rehydration after drought stress have not been reported. To assess the drought tolerance and compensatory capacity of DSEs, the following DSEs were investigated in this study using solid-liquid screening and potting tests under different drought gradients, rehydration conditions, and field water-holding capacities: Stagonosporopsis lupini, Microsphaeropsis cytisi, Macrophomina pseudophaseolina, Paraphoma radicina, Alternaria alstroemeriae, Alternaria tellustris, and Papulaspora equi. The results showed that M. pseudophaseolina reached the maximum diameter for plate growth in only 4 d. In a liquid shaker, the biomass of S. lupini peaked after rehydration. The Mantel heatmap indicated that lipid metabolites were significantly expressed in M. pseudophaseolina and S. lupini under drought stress. Correlations between drought tolerance indexes and amino acid metabolites increased dramatically in both DSEs after rehydration. Moreover, in rehydration after drought, the treatments inoculated with M. pseudophaseolina and S. lupini showed significant increases in root weight of 20.36% and 23.82%, respectively, compared with the uninoculated treatment.

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Aging interventions have progressed in recent years due to the growing curiosity about how lifestyle impacts longevity. This study assessed the effects of SRW Laboratories' Cel System nutraceutical range on epigenetic methylation patterns, inflammation, physical performance, body composition, and epigenetic biomarkers of aging. A 1-year study was conducted with 51 individuals, collecting data at baseline, 3 months, 6 months, and 12 months. Participants were encouraged to walk 10 minutes and practice 5 minutes of mindfulness daily. Significant improvements in muscle strength, body function, and body composition metrics were observed. Epigenetic clock analysis showed a decrease in biological age with significant reductions in stem cell division rates. Immune cell subset analysis indicated significant changes, with increases in eosinophils and CD8T cells and decreases in B memory, CD4T memory, and T-regulatory cells. Predicted epigenetic biomarker proxies (EBPs) showed significant changes in retinol/TTHY, a regulator of cell growth, proliferation, and differentiation, and deoxycholic acid glucuronide levels, a metabolite of deoxycholic acid generated in the liver. Gene ontology analysis revealed significant CpG methylation changes in genes involved in critical biological processes related to aging, such as oxidative stress-induced premature senescence, pyrimidine deoxyribonucleotide metabolic process, TRAIL binding, hyaluronan biosynthetic process, neurotransmitter loading into synaptic vesicles, pore complex assembly, collagen biosynthetic process, protein phosphatase 2A binding activity, and activation of transcription factor binding. Our findings suggest that the Cel System supplement range may effectively reduce biological age and improve health metrics, warranting further investigation into its mechanistic pathways and long-term efficacy.

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Amidst rising global prevalence of metabolic syndrome, the associated risk of non-alcoholic fatty liver disease (NAFLD) is also rapidly increasing. The pathogenesis of NAFLD starts with fat accumulation and progresses through inflammation and fibrotic sequel, often involving complex molecular mechanisms involving de novo lipogenesis. Stearoyl-CoA desaturase 1 (SCD1) enzyme, expressed in liver and adipose tissue, converts saturated fatty acids to monounsaturated fatty acids (MUFAs), contributing to triglyceride and cholesterol ester formation. In this study, potential SCD1 inhibitors were screened using the ZINC database of curated medically-approved drugs by virtual screening, molecular docking, and molecular dynamics simulations. The top-scoring five ligands with strong binding affinity against SCD1 were ZINC000003831151 > ZINC000001540998 > ZINC000003830713 > ZINC000000897251 > ZINC000002005305, which showed stable protein-ligand complexation and favorable pharmacokinetic attributes. The top ligand, Montelukast, was experimentally validated for its pharmacological efficacy in an in vitro cell culture model of steatosis (NAFLD). Montelukast showed a dose-dependent decrease in hepatic fat accumulation, reduced levels of free radicals, and lowered oxidative stress (P < 0.05). These outcomes suggest Montelukast to be a potential SCD1 inhibitor, with anti-NAFLD efficacy. These findings open new avenues for therapeutic development of the top 5 ligands in metabolic disorders involving SCD1.

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