Vitamin D plays an active role beyond mineral metabolism and skeletal health, including regulation of the immune system. Vitamin D deficiency is widely prevalent, and observational studies link low vitamin D status to a risk of infections and auto-immune disorders. Reports indicate an inverse relationship between vitamin D status and such conditions. This review details vitamin D signalling interactions with the immune system and provides experimental and clinical evidence evaluating vitamin D status, vitamin D supplementation and host susceptibility to infections, inflammation and auto-immunity. The published literature including related reviews, systematic reviews, meta-analyses, randomised controlled trials (RCTs), observational studies and basic science reports have been synthesised. Meta-analyses of observational studies have demonstrated a link between low vitamin D status and risk of acute respiratory infections, COVID-19 disorders, multiple sclerosis, type 1 diabetes (T1DM), inflammatory bowel disease (IBD), systemic lupus erythematosus and other auto-immune disorders. Observational studies suggest that vitamin D supplementation may protect against several infectious and auto-immune conditions. Meta-analyses of RCTs had mixed results, demonstrating a small protective role for vitamin D supplementation against acute respiratory infections, especially in those with vitamin D deficiency and children, and providing modest benefits for the management of T1DM and IBD. Vitamin D status is inversely associated with the incidence of several infectious and auto-immune conditions. Supplementation is recommended for those with vitamin D deficiency or at high risk of deficiency, and it might provide additional benefit in acute respiratory infections and certain auto-immune conditions.

Vitamin D: immune function, inflammation, infections and auto-immunity.

This draft clinical practice guideline for the diagnosis, treatment and prevention of vitamin D deficiency is an update from a previous 2016 document. An analysis of the relevant literature data was carried out, with particular attention to meta-­analyzes, randomized clinical trials and systematic reviews published over the past 5 years. The updated recommendations were discussed and revised by the leading endocrinologists of the Russian Federation, who have expert status in this issue.The classification of 25(OH)D levels has been revised (in particular, the target range of 25(OH)D values has been specified), recommendations have been developed for screening of the disorders associated with vitamin D deficiency. The concept of vitamin D-associated toxicity and recommendations for its diagnosis and prevention have been introduced. Also, indications for the assessment of other vitamin D metabolites besides 25(OH)D, the main marker of vitamin D status, have been indicated.The section regarding treatment of vitamin D deficiency has been expanded and corrected. The major additions concerned the replenishment of the vitamin D deficiency and insufficiency in certain categories of patients (particularly, in the presence of the chronic kidney disease and autoimmune diseases, as well as in pregnant women) and monitoring of the effectiveness and safety of the therapy. The indications for prescribing active metabolites of vitamin D have been adjusted. Recommendations for the prevention of vitamin D deficiency in the general population have also been revised, taking into account large randomized clinical trials, meta-analyzes and systematic reviews of recent years.This publication is an expanded version of the federal guidelines.

Draft federal clinical practice guidelines for the diagnosis, treatment, and prevention of vitamin D deficiency

Vitamin D supplementation has been considered a possible treatment to reduce the risk of disease activity and progression in people with multiple sclerosis (MS). However, its effect on disease symptoms remains unclear. The aim of this meta-analysis was to conduct a systematic review to assess the effect of vitamin D on fatigue in this population. The systematic review was conducted using the MEDLINE, Cochrane Library, Embase and Web of Science databases from inception to May 2023. Randomized controlled trials (RCTs) reporting pre–post changes in fatigue after vitamin D supplementation were included. Pooled effect sizes and 95% confidence intervals (95% CIs) were calculated by applying a random effects model with Stata/SE (Version 16.0; StataCorp., College Station, TX, USA). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. A total of five studies with 345 individuals (271 females; age range: 25.4–41.1 years) were included. A significant reduction in fatigue was perceived when vitamin D supplementation was compared with a control group: −0.18 (95% CI: −0.36 to −0.01; I2 = 0%). Thus, our findings show that the therapeutic use of vitamin D on fatigue in people with MS could be considered. Nevertheless, due to the lack of agreement on the dose to be applied, it is recommended to use it under medical prescription.

/pdf/effect-of-vitamin-d-supplementation-on-fatigue-in-multiple-3bpx5zq2.pdf

Effect of Vitamin D Supplementation on Fatigue in Multiple Sclerosis: A Systematic Review and Meta-Analysis

This study reported the efficacy and underlying mechanism of agrimonolide (AM) in treating colon cancer.Colon cancer-AM-related targets were screened from online database. AM targets for colon cancer were identified by Venn diagram. Main molecular function, biological process, cellular component and pathways associated with AM targets for colon cancer were analyzed by GO and KEGG enrichment analysis. Relationship of the 10 core targets of AM for colon cancer with the top 15 BP and KEGG pathways was analyzed by Cytoscape software. A "component-target-pathway" network was constructed to select the hub genes of AM for colon cancer. AM effects on colon cancer cell viability, proliferation, invasion, migration and apoptosis were researched by CCK-8, colony formation, Transwell invasion, wound healing and flow cytometry assays. Tumor-bearing nude mice models were constructed and given AM treatment. Hub gene expression in cells/tissues was detected by Western blot.A total of 107 targets were selected as AM targets for colon cancer. The 10 core targets were related to the top 15 biological process terms and KEGG pathways. PI3K, AKT and mTOR were selected as the hub genes of AM for colon cancer. AM weakened colon cell proliferation, invasion, migration and apoptosis inhibition, and suppressed colon cell in vivo growth. AM up-regulated Caspase-3 and BAX proteins, down-regulated C-Myc, Cyclin D1 and BCL-2 proteins, and inactivated the PI3K/AKT/mTOR pathway both in vitro and in vivo.AM suppressed colon cancer progression through inactivating the PI3K/AKT/mTOR pathway. It may be useful for colon cancer treatment. 

Elucidating the Mechanism of Agrimonolide in Treating Colon Cancer Based on Network Pharmacology

Introduction: Asparagus (Asparagus officinalis) is a perennial flowering plant species. Its main components have tumor-prevention, immune system-enhancement, and anti-inflammation effects. Network pharmacology is a powerful approach that is being applied increasingly to research of herbal medicines. Herb identification, study of compound targets, network construction, and network analysis have been used to elucidate how herbal medicines work. However, the interaction of bioactive substances from asparagus with the targets involved in multiple myeloma (MM) has not been elucidated. We explored the mechanism of action of asparagus in MM through network pharmacology and experimental verification. Methods: The active ingredients and corresponding targets of asparagus were acquired from the Traditional Chinese Medicine System Pharmacology database, followed by identification of MM-related target genes using GeneCards and Online Mendelian Inheritance in Man databases, which were matched with the potential targets of asparagus. Potential targets were identified and a target network of traditional Chinese medicine was constructed. The STRING database and Cytoscape were utilized to create protein–protein interaction (PPI) networks and further screening of core targets. Results: The intersection of target genes and core target genes of the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway was enriched, the top-five core target genes were selected, and the binding affinity of corresponding compounds to the top-five core targets was analyzed using molecular docking. Network pharmacology identified nine active components of asparagus from databases based on oral bioavailability and drug similarity, and predicted 157 potential targets related to asparagus. Enrichment analyses showed that “steroid receptor activity” and the “PI3K/AKT signaling pathway” were the most enriched biological process and signaling pathway, respectively. According to the top-10 core genes and targets of the PPI pathway, AKT1, interleukin (IL)-6, vascular endothelial growth factor (VEGF)A, MYC, and epidermal growth factor receptor (EGFR) were selected for molecular docking. The latter showed that five core targets of the PI3K/AKT signaling pathway could bind to quercetin, among which EGFR, IL-6, and MYC showed strong docking, and the diosgenin ligand could bind to VEGFA. Cell experiments showed that asparagus, through the PI3K/AKT/NF-κB pathway, inhibited the proliferation and migration of MM cells, and caused retardation and apoptosis of MM cells in the G0/G1 phase. Discussion: In this study, the anti-cancer activity of asparagus against MM was demonstrated using network pharmacology, and potential pharmacological mechanisms were inferred using in vitro experimental data.

https://www.frontiersin.org/articles/10.3389/fphar.2023.1076815/pdf

Mechanism of action of Asparagus officinalis extract against multiple myeloma using bioinformatics tools, in silico and in vitro study

Background Despite the vitamin D treatment in patients with multiple sclerosis (MS), there continues to be controversial discrepancy in outcomes according to the current research. Many systematic reviews have evaluated the effect of vitamin D as an adjuvant treatment in patients with MS; however, there is no consensus on the optimum administration time and dosage of vitamin D intake. A meta-analysis for exploring the different administration time and dosage of vitamin D is warranted. Methods Randomized controlled trials (RCTs) on the effect of different administration time and dosage of vitamin D in patients with MS were recorded within 7 databases. This meta-analysis was performed with 2 clinical outcomes: EDSS (Expanded Disability Status Scale) and relapses during research. Results The pooled results indicated that receiving different administration time and dosage of vitamin D as an adjuvant treatment had no significant therapeutic effect on MS according to the EDSS scores and relapses during research. Conclusion According to our meta-analysis, the administration of vitamin D in different dosages (ranging from 2,857 to 14,007 IU/day) and treatment period (ranging from 6 to 24 months) did not affect the clinical outcomes (EDSS and relapses during research) in patients with MS. Additional RCTs should be conducted to explore whether a longer duration and a larger dosage of vitamin D without serious adverse effects might produce therapeutic effects in patients with MS.

The Effect of Different Administration Time and Dosage of Vitamin D Supplementation in Patients with Multiple Sclerosis: A Meta-Analysis of Randomized Controlled Trials.

Prevalence, in-hospital mortality, and factors related to neurogenic pulmonary edema after spontaneous subarachnoid hemorrhage: a systematic review and meta-analysis

Asparagus (ASP) is a well-known traditional Chinese medicine with nourishing, moistening, fire-clearing, cough-suppressing, and intestinal effects. In addition, it exerts anti-inflammatory, antioxidant, anti-aging, immunity-enhancing, and anti-tumor pharmacological effect. The anti-tumor effect of ASP has been studied in hepatocellular carcinoma. However, its action and pharmacological mechanism in colorectal cancer (CRC) are unclear. The present study aimed to identify the potential targets of ASP for CRC treatment using network pharmacology and explore its possible therapeutic mechanisms using in vitro and in vivo experiments. The active compounds and potential targets of ASP were obtained from the TCMSP database, followed by CRC-related target genes identification using GeneCards and OMIM databases, which were matched with the potential targets of ASP. Based on the matching results, potential targets and signaling pathways were identified by protein-protein interaction (PPI), gene ontology (GO) functions, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Finally, in vitro and in vivo experiments were performed to further validate the anti-cancer effects of ASP on CRC. Network pharmacology analysis identified nine active components from ASP from the database based on oral bioavailability and drug similarity index, and 157 potential targets related to ASP were predicted. The PPI network identified tumor protein 53 (TP53), Fos proto-oncogene, AP-1 transcription factor subunit (FOS), and AKT serine/threonine kinase 1 (AKT1) as key targets. GO analysis showed that ASP might act through response to wounding, membrane raft, and transcription factor binding. KEGG enrichment analysis revealed that ASP may affect CRC through the phosphatidylinositol-4,5-bisphosphate 3-kinase PI3K/AKT/mechanistic target of rapamycin kinase (mTOR) signaling pathway. In vitro, ASP inhibited cell proliferation, migration, and invasion of HCT116 and LOVO cells, and caused G0/G1 phase arrest and apoptosis in CRC cells. In vivo, ASP significantly inhibited the growth of CRC transplanted tumors in nude mice. Furthermore, pathway analysis confirmed that ASP could exert its therapeutic effects on CRC by regulating cell proliferation and survival through the PI3K/AKT/mTOR signaling pathway. This study is the first to report the potential role of ASP in the treatment of colorectal cancer.

Combining Network Pharmacology and Experimental Validation to Study the Action and Mechanism of Water extract of Asparagus Against Colorectal Cancer

Abstract Background Posterior reversible encephalopathy syndrome (PRES) is a rare disease characterized by reversible subcortical vasogenic brain edema. Neuromyelitis optica spectrum disorder (NMOSD) is a frequent neurological autoimmune disease that is rarely reported to complicate PRES. Case presentation Here, we report a case of neuromyelitis optica (NMO) concurrent with PRES. A 50-year-old woman presented with severe impairment of her health visual acuity, with significantly worsening of the motor weakness in both lower limbs during methylprednisolone therapy after her diagnosis of NMO. MRI showed new-onset brain edematous lesions of the bilateral frontal, occipital, and parietal lobes. PRES was considered. Her vision impairment and weakness of the extremities were alleviated after antihypertensive treatment and dehydration. The edema lesions detected by MRI also completely disappeared. Conclusions We reviewed 14 cases of NMO with PRES and concluded that the etiology of NMOSD concurrent PRES may be multifactorial, involving pathogenic IgGs against aquaporin-4 (AQP-4) and immunotherapy treatment. Different underlying pathogeneses require different treatment approaches. 

https://bmcneurol.biomedcentral.com/counter/pdf/10.1186/s12883-022-02985-8

The pathogenesis and treatment of posterior reversible encephalopathy syndrome after neuromyelitis optica spectrum disorder: a case report and literature review

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Papers

The Effect of Different Administration Time and Dosage of Vitamin D Supplementation in Patients with Multiple Sclerosis: A Meta-Analysis of Randomized Controlled Trials.

Prevalence, in-hospital mortality, and factors related to neurogenic pulmonary edema after spontaneous subarachnoid hemorrhage: a systematic review and meta-analysis

Combining Network Pharmacology and Experimental Validation to Study the Action and Mechanism of Water extract of Asparagus Against Colorectal Cancer

The pathogenesis and treatment of posterior reversible encephalopathy syndrome after neuromyelitis optica spectrum disorder: a case report and literature review