Vitamin D supplementation for the prevention of total cancer incidence and mortality: An updated systematic review and meta-analysis.

Introduction: Previous randomized controlled trials (RCTs) and meta-analyses of RCTs evaluating vitamin D supplementation for the prevention of cancer incidence and mortality have found inconsistent results and no meta-analysis has assessed the quality of the evidence available. We, therefore, aimed to perform an updated meta-analysis by including recent large-scale RCTs and assessing the quality of the pooled evidence. Methods: We searched several databases and trial registers from inception to April 2022. We used a random-effects model to estimate pooled risk ratios (RRs) and 95% confidence intervals (CIs). We used the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) considerations to evaluate the certainty of evidence. Results: We included 13 RCTs in our study. Vitamin D supplementation had no effect on the risk of total cancer incidence (RR 0.99, 95% CI: 0.94-1.04; I 2 = 0%), total cancer mortality (RR 0.93, 95% CI: 0.84-1.03; I 2 = 24%) and total mortality (RR 0.92, 95% CI: 0.82-1.04; I 2 = 36%). The overall quality of evidence was high for all outcomes. Discussion: Vitamin D supplementation is ineffective in reducing total cancer incidence and mortality in largely vitamin D-replete older adult populations. Future research should be based on populations with a higher prevalence of vitamin D deficiency and should involve more extended follow-up periods. Study protocol: PROSPERO database, CRD42021285401.

Pharmacological insights into the multifaceted biological properties of quinic acid.

Quinic acid is a cyclohexanecarboxylic acid contained in the extracts of several parts of medicinal plants including Haematocarpus validus, Hypericum empetrifolium, Achillea pseudoaleppica, Rumex nepalensis, Phagnalon saxatile subsp. saxatile, Coffea arabica, Ziziphus lotus L, and Artemisia annua L … etc. Currently, in vitro and in vivo pharmacological studies showed that quinic acid exhibits various biological activities, such as antioxidant, antidiabetic, anticancer activity, antimicrobial, antiviral, aging, protective, anti-nociceptive and analgesic effects. Indeed, QA possesses an important antibacterial effect which could be explained by the fact that this molecule modules the functions of ribosomes and the synthesis of aminoacyl-tRNAs, modifications the levels of glycerophospholipids and fatty acids and disruption of the oxidative phosphorylation pathway thereby causing interference with membrane fluidity. The antidiabetic activity of AQ is achieved by stimulation of insulin secretion via the mobilization of Ca2+ from intracellular reserves and the increase in the NAD(P)H/NAD(P)+ ratio. Its anticancer effect is through the promotion of apoptosis, inhibition of activator protein 1 (AP-1) and signaling pathways involving protein kinase C (PKC) and certain mitogen-activated protein kinases (MAPKs), resulting in the downregulation of matrix metallopeptidase 9 (MMP-9) expression. Therefore, this review describes the main research work carried out on the biological properties of AQ and the mechanism of action underlying some of these effects, as well as the investigations of the main pharmacokinetic studies.

Identification of Novel and Safe Fungicidal Molecules against Fusarium oxysporum from Plant Essential Oils: In Vitro and Computational Approaches.

Phytopathogenic fungi are serious threats in the agriculture sector especially in fruit and vegetable production. The use of plant essential oil as antifungal agents has been in practice from many years. Plant essential oils (PEOs) of Cuminum cyminum, Trachyspermum ammi, Azadirachta indica, Syzygium aromaticum, Moringa oleifera, Mentha spicata, Eucalyptus grandis, Allium sativum, and Citrus sinensis were tested against Fusarium oxysporum. Three phase trials consist of lab testing (MIC and MFC), field testing (seed treatment and foliar spray), and computer-aided fungicide design (CAFD). Two concentrations (25 and 50 µl/ml) have been used to asses MIC while MFC was assessed at four concentrations (25, 50, 75, and 100 µl/ml). C. sinensis showed the largest inhibition zone (47.5 and 46.3 m2) for both concentrations. The lowest disease incidence and disease severity were recorded in treatments with C. sinensis PEO. Citrus sinensis that qualified in laboratory and field trials was selected for CAFD. The chemical compounds of C. sinensis PEO were docked with polyketide synthase beta-ketoacyl synthase domain of F. oxysporum by AutoDock Vina. The best docked complex was formed by nootkatone with -6.0 kcal/mol binding affinity. Pharmacophore of the top seven C. sinensis PEO compounds was used for merged pharmacophore generation. The best pharmacophore model with 0.8492 score was screened against the CMNP database. Top hit compounds from screening were selected and docked with polyketide synthase beta-ketoacyl synthase domain. Four compounds with the highest binding affinity and hydrogen bonding were selected for confirmation of lead molecule by doing MD simulation. The polyketide synthase-CMNPD24498 showed the highest stability throughout 80 ns run of MD simulation. CMNPD24498 (FW054-1) from Verrucosispora was selected as the lead compound against F. oxysporum.

In Silico and In Vitro Screening Constituents of Eclipta alba Leaf Extract to Reveal Antimicrobial Potential.

Phytochemicals have been shown to possess multiple bioactives and have been reported to showcase many medicinal effects. A similar kind of evaluation of phytoconstituents for their antimicrobial action has been reported, based on in vitro and in silico data. The goal of the research was to explore bioactive phytoconstituents of Eclipta alba leaf for antimicrobial activity. The antimicrobial activity was validated by both molecular docking and antimicrobial assay. Bioactive metabolites were identified using GC-MS. The antimicrobial and antimycobacterial activity of Eclipta alba leaves was investigated using the Kirby-Bauer well diffusion method and the rapid culture-MGIT™ DST method against a variety of human pathogens, as well as Mycobacterium tuberculosis (H37Rv) and Mycobacterium tuberculosis bacteria resistant to isoniazid and rifampicin. Eclipta alba's GC-MS studies confirmed the detection of 17 bioactive constituents. The extract demonstrates the highest antibacterial activity against Escherichia coli (sensitive), Pseudomonas aeruginosa (sensitive) and methicillin-resistant Staphylococcus aureus (MRSA), and Pseudomonas aeruginosa susceptible and MRSA (sensitive) with zone of inhibition of 27 mm, 24 mm, and 32 mm respectively. The extract showed no effect on Mycobacterium tuberculosis (H37Rv) and Mycobacterium tuberculosis bacteria resistant to isoniazid and rifampicin in antimycobacterial activity testing. Molecular docking investigation revealed that three compounds (phthalic acid, isobutyl octadecyl ester, hexadecanoic acid, 1(hydroxymethyl)1,2-ethanediylester, and 2,myristynoyl pantetheine) have generated the best results in terms of binding energies and significant interactions with key residues of target protein 3-hydroxydecanoyl-acyl carrier protein dehydratase (FabA) and confirm its activity as antimicrobial inhibitors. These two-dimensional plots show significant protein-ligand binding interactions (van der Waals interactions, hydrogen bond, alkyl, and Pi-alkyl interactions). ADMET (absorption, distribution, metabolism, excretion, and toxicity) results additionally support the drug-likeness characteristics of concluded potential compounds. The experimental and computational results demonstrated that methanolic extract of Eclipta alba leaves had antimicrobial effects for specific infections due to the presence of phytochemical compounds.

Identification of Effective and Nonpromiscuous Antidiabetic Drug Molecules from Penicillium Species.

Diabetes mellitus (DM) is a very common metabolic disorder/disease. The deterioration of ß-cells by autoimmune system is the hallmark of this disease. Thioredoxin-Interacting Protein (TXNIP) is responsible for ß-cells degradation by T-cells in the pancreas. This protein had been declared a good drug target for controlling DM. Lots of side effects have been reported as a result of long-time consumption of conventional antidiabetic drugs. The development of new and effective drugs with the minimal side effects needs time. TXNIP was selected as a target for Computer-Aided Drug Design. The antidiabetic fungal metabolite compounds were selected from the literature. The compounds were screened for their drug-likeness properties by DruLiTo and DataWarior tools. Twenty-two drug-like fungal compounds were subjected to Quantitative Structure-Activity Relationship (QSAR) analysis by using CheS-Mapper 2.0. The lowest (0.01) activity cliff was found for three compounds: Pinazaphilone A, Pinazaphilone B, and Chermesinone A. The highest value for apol (81.76) was shown by Asperphenamate, while Albonoursin and Sterenin L showed highest score (40.66) for bpol. The lowest value (0.46) for fractional molecular frame (FMF) was calculated for Pinazaphilone A and Pinazaphilone B. TPSA for Pinazaphilone A and Pinazaphilone B was 130.51 Å2. log P < 5 was observed for all the twenty-two compounds. Molecular docking of fungal compounds with TXNIP was done by AutoDock Vina. The binding energy for complexes ranged between -9.2 and -4.6 kcal/mol. Four complexes, TXNIP-Pinazaphilone A, TXNIP-Pinazaphilone B, TXNIP-Asperphenamate, and TXNIP-Sterenin L, were selected for MD simulation to find out the best lead molecule. Only one complex, TXNIP-Pinazaphilone B, showed a stable conformation throughout the 80 ns run of MD simulation. Pinazaphilone B derived from the Penicillium species fungi was selected as the lead molecule for development of antidiabetic drug having the least side effects.

Natural therapeutics and nutraceuticals for lung diseases: Traditional significance, phytochemistry, and pharmacology.

BACKGROUND: Lung diseases including chronic obstructive pulmonary disease (COPD), infections like influenza, acute respiratory distress syndrome (ARDS), asthma and pneumonia lung cancer (LC) are common causes of sickness and death worldwide due to their remoteness, cold and harsh climatic conditions, and inaccessible health care facilities. PURPOSE: Many drugs have already been proposed for the treatment of lung diseases. Few of them are in clinical trials and have the potential to cure infectious diseases. Plant extracts or herbal products have been extensively used as Traditional Chinese Medicine (TCM) and Indian Ayurveda. Moreover, it has been involved in the inhibition of certain genes/protiens effects to promote regulation of signaling pathways. Natural remedies have been scientifically proven with remarkable bioactivities and are considered a cheap and safe source for lung disease. METHODS: This comprehensive review highlighted the literature about traditional plants and their metabolites with their applications for the treatment of lung diseases through experimental models in humans. Natural drugs information and mode of mechanism have been studied through the literature retrieved by Google Scholar, ScienceDirect, SciFinder, Scopus and Medline PubMed resources against lung diseases. RESULTS: In vitro, in vivo and computational studies have been explained for natural metabolites derived from plants (like flavonoids, alkaloids, and terpenoids) against different types of lung diseases. Probiotics have also been biologically active therapeutics against cancer, anti-inflammation, antiplatelet, antiviral, and antioxidants associated with lung diseases. CONCLUSION: The results of the mentioned natural metabolites repurposed for different lung diseases especially for SARS-CoV-2 should be evaluated more by advance computational applications, experimental models in the biological system, also need to be validated by clinical trials so that we may be able to retrieve potential drugs for most challenging lung diseases especially SARS-CoV-2.

The Relationship Between Vitamin D Levels and Severity in Illness in COVID-19 Patients: A Cross-Sectional Study.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic hit the world badly with high mortality. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection increased the COVID-19 burden among developed and developing countries due to the unavailability of proven treatment options. Vitamin D has many important anti-inflammatory, immunomodulator, and anti-viral functions. The present study was conducted to evaluate the relationship between Vitamin D in COVID-19. METHODS: A cross-sectional study was conducted at a tertiary care hospital in Patna, India. All the patients were enrolled during the period of 3.5 months. A chemiluminescence-based immunoassay analyzer was used to quantify Vitamin D among COVID-19 patients. The study compared Vitamin D deficiency and insufficiency among different groups, i.e., age, sex, BMI, comorbidity, etc. Diabetes and hypertension were evaluated as risk factors for mortality. RESULTS: A total of 225 patients were investigated. Of these, 13.6% had Vitamin D deficiency and 38.9% had insufficiency. Vitamin D level was statistically significant among different age groups, sex, and smokers. Patients aged >60 years were 23 times more likely to have a severe illness (adjusted OR (aOR) 23.53, 95%CI 4.67-118.61), whereas those aged 40 to 60 years were 11 times more likely to have a severe illness (aOR 10.86, 95%CI 2.39-49.31). Patients with many comorbidities, on the other hand, had a tenfold greater chance of severe COVID-19 (aOR 9.94, 95%CI 2.47-39.88). A deficiency of vitamin D increased the chance of a serious illness by nearly five times (aOR 4.72, 95%CI 1.31-17.03). CONCLUSION: Vitamin D level was associated with severity of illness; it can be used to estimate the prognosis of COIVD-19 patients and aid in the modification of treatment protocols.

Bovine Follicular Fluid and Extracellular Vesicles Derived from Follicular Fluid Alter the Bovine Oviductal Epithelial Cells Transcriptome.

While follicular fluid (FF) is well known to provide an optimal environment for oogenesis, its functional roles following its release into the oviduct during ovulation are currently elusive. We hypothesized that FF and FF-derived extracellular vesicles (EVs) may be conveyors of signals capable of inducing functionally-relevant transcriptional responses in oviductal cells. The aim of this study was, therefore, to evaluate the effect of FF and FF-derived EVs on the transcriptome of primary bovine oviductal epithelial cells (BOECs). We examined the gene expression of BOECs in three conditions: BOECs cultured with FF, FF-derived EVs, and without supplementations. For each condition, cells were cultured for 6 and 24 h. RNA sequencing results revealed that FF had a stronger effect on BOECs gene expression compared to EVs. We detected 488 and 1998 differentially expressed genes (DEGs) with FF treatment in 6 and 24 h, respectively, whereas only 41 DEGs were detected at 6 h following EV treatment. Pathway analysis of the FF-induced DEGs showed that several pathways were highly enriched, notably oxidative phosphorylation, thermogenesis, arachidonic acid metabolism, and steroid hormone biosynthesis. Some of these pathways have a role in sperm survival, fertilization, and early embryo development. In conclusion, the findings of our study demonstrate for the first time that bovine FF and FF-derived EVs can induce changes in the gene expression of the bovine oviductal cells which, although observed in vitro, may be reflective of in vivo responses which may contribute to a favorable periconceptional microenvironment for sperm survival, fertilization, and early embryo development.