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Nutrients Jan 2021Vitamin D is an essential component of immune function and childhood deficiency is associated with an increased risk of acute lower respiratory infections (ALRIs)....
Vitamin D is an essential component of immune function and childhood deficiency is associated with an increased risk of acute lower respiratory infections (ALRIs). Globally, the leading childhood respiratory pathogens are , respiratory syncytial virus and the influenza virus. There is a growing body of evidence describing the innate immunomodulatory properties of vitamin D during challenge with respiratory pathogens, but recent systematic and unbiased synthesis of data is lacking, and future research directions are unclear. We therefore conducted a systematic PubMed literature search using the terms "vitamin D" and "" or "Respiratory Syncytial Virus" or "Influenza". A priori inclusion criteria restricted the review to in vitro studies investigating the effect of vitamin D metabolites on human innate immune cells (primary, differentiated or immortalised) in response to stimulation with the specified respiratory pathogens. Eleven studies met our criteria. Despite some heterogeneity across pathogens and innate cell types, vitamin D modulated pathogen recognition receptor (PRRs: Toll-like receptor 2 (TLR2), TLR4, TLR7 and nucleotide-binding oligomerisation domain-containing protein 2 (NOD2)) expression; increased antimicrobial peptide expression (LL-37, human neutrophil peptide (HNP) 1-3 and β-defensin); modulated autophagosome production reducing apoptosis; and modulated production of inflammatory cytokines (Interleukin (IL) -1β, tumour necrosis factor-α (TNF-α), interferon-ɣ (IFN-ɣ), IL-12p70, IFN-β, Regulated on Activation, Normal T cell Expressed (RANTES), IL-10) and chemokines (IL-8 and C-X-C motif chemokine ligand 10 (CXCL10)). Differential modulation of PRRs and IL-1β was reported across immune cell types; however, this may be due to the experimental design. None of the studies specifically focused on immune responses in cells derived from children. In summary, vitamin D promotes a balanced immune response, potentially enhancing pathogen sensing and clearance and restricting pathogen induced inflammatory dysregulation. This is likely to be important in controlling both ALRIs and the immunopathology associated with poorer outcomes and progression to chronic lung diseases. Many unknowns remain and further investigation is required to clarify the nuances in vitamin D mediated immune responses by pathogen and immune cell type and to determine whether these in vitro findings translate into enhanced immunity and reduced ALRI in the paediatric clinical setting.
Topics: Child; Child, Preschool; Cytokines; Humans; Immunity, Innate; Immunomodulation; Infant; Influenza A virus; Influenza, Human; Pneumonia, Pneumococcal; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Respiratory Tract Infections; Streptococcus pneumoniae; Vitamin D
PubMed: 33478006
DOI: 10.3390/nu13010276 -
Current Medicinal Chemistry 2017Crohn's disease (CD) and ulcerative colitis (UC) are classified under inflammatory bowel disease (IBD) which has been linked to a multifaceted etiology involving both... (Review)
Review
Crohn's disease (CD) and ulcerative colitis (UC) are classified under inflammatory bowel disease (IBD) which has been linked to a multifaceted etiology involving both environmental and genetic factors that intersect with the vitamin D pathway. Dysfunctions in innate immune defense mechanisms in the epithelial compartment of the intestine play a crucial role in the pathogenesis of IBD. Symptoms of IBD are caused by excessive immune responses to luminal bacteria, and vitamin D has been shown to play a role in intestinal defense by aiding in the suppression of microbial invasion into the epithelium. Vitamin D, as an immunomodulator, can modify the innate immune response of the body. Vitamin D attenuates the transcription of pro-inflammatory cytokines that are upregulated in the event of epithelial stress common in patients with IBD. Vitamin D deficiency was identified in 82% of IBD patients compared to the 31% national average and has been linked to defective epithelial processes at both genomic and proteomic levels. Mucosal damage and an impaired immune response are at the center of IBD, and vitamin D aids in sustaining the structural integrity of epithelial cells while enhancing innate immune responses in the mucosa. Here we provide a systematic review of the pathophysiological effects of cytokines in IBD in the presence of vitamin D deficiency. Also, analysis of the immunomodulatory effect of vitamin D in regulating immunopathogenic factors like chemokines, growth factors, and human defensins will enhance knowledge of the underlying molecular mechanisms of the therapeutic role of vitamin D in IBD and thus aid in the development of better patient management strategies.
Topics: Humans; Immunity; Inflammatory Bowel Diseases; Vitamin D
PubMed: 27784213
DOI: 10.2174/0929867323666161026124951 -
Revista Medica Del Instituto Mexicano... Jul 2023Single nucleotide polymorphisms (SNPs) have been reported to play an important role in the etiology of dental caries. The aim of this research was, through a systematic... (Review)
Review
Single nucleotide polymorphisms (SNPs) have been reported to play an important role in the etiology of dental caries. The aim of this research was, through a systematic review, to identify SNPs recently associated with dental caries in pediatric populations. We included studies performed in humans up to 18 years of age that evaluated the relationship between SNPs and dental caries from 2017 to 2022. Articles that covered other study variables were excluded. PubMed, ScienceDirect and Web of Science were used to search for information and the included articles were evaluated with one of the Joanna Briggs Institute's tools. Twenty-five articles were selected, 60% of which were given high methodological quality. A total of 10,743 research subjects, ranging in age from 20 months to 17 years, participated in the study. The SNPs considered risk factors were identified in the genes miRNA202, VDR, AMELX, TUFT1, KLK4, MBL2, ENAM, DEFB1, HLA-DRB1, TAS1R1, DSPP, RUNX2 and MMP13; those considered protective factors were identified in the genes MMP20, AMBN, MMP9, TIMP2, TNF-α, VDR, IL1B, ENAM and HLA-DRB1. This systematic review presents the genetic polymorphisms that are associated with the etiology of caries in children and adolescents, some of which act as risk factors and others as protective factors against the disease.
Topics: Adolescent; Humans; Child; Dental Caries; HLA-DRB1 Chains; Polymorphism, Single Nucleotide; Mannose-Binding Lectin; beta-Defensins; MicroRNAs
PubMed: 37540722
DOI: 10.5281/zenodo.8200501 -
JBJS Reviews Mar 2023Periprosthetic joint infection (PJI) is a devastating complication after total joint arthroplasty (TJA), with treatment failure occurring in 12% to 28% after 2-stage... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Periprosthetic joint infection (PJI) is a devastating complication after total joint arthroplasty (TJA), with treatment failure occurring in 12% to 28% after 2-stage revision. It is vital to identify diagnostic tools indicative of persistent infection or treatment failure after 2-stage revision for PJI.
METHODS
The Cochrane Library, PubMed (MEDLINE), and EMBASE were searched for randomized controlled trials and comparative observational studies published before October 3, 2021, which evaluated the utility of serum/plasma biomarkers (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], interleukin-6 [IL-6], fibrinogen, D-dimer), synovial biomarkers (white blood cell [WBC] count, neutrophil percentage [PMN %], alpha-defensin [AD], leukocyte esterase [LE]), tissue frozen section, tissue culture, synovial fluid culture, or sonicated spacer fluid culture indicative of persistent infection before the second stage of 2-stage revision for PJI or treatment failure after 2-stage revision for PJI.
RESULTS
A total of 47 studies including 6,605 diagnostic tests among 3,781 2-stage revisions for PJI were analyzed. Among those cases, 723 (19.1%) experienced persistent infection or treatment failure. Synovial LE (sensitivity 0.25 [0.10-0.47], specificity 0.99 [0.93-1.00], positive likelihood ratio 14.0 [1.45-135.58]) and serum IL-6 (sensitivity 0.52 [0.33-0.70], specificity 0.92 [0.85-0.96], positive likelihood ratio 7.90 [0.86-72.61]) had the highest diagnostic accuracy. However, no biomarker was associated with a clinically useful negative likelihood ratio. In subgroup analysis, synovial PMN %, synovial fluid culture, serum ESR, and serum CRP had limited utility for detecting persistent infection before reimplantation (positive likelihood ratios ranging 2.33-3.74; negative likelihood ratios ranging 0.31-0.9) and no utility for predicting failure after the second stage of 2-stage revision.
CONCLUSIONS
Synovial WBC count, synovial PMN %, synovial fluid culture, serum ESR, and serum CRP have modest sensitivity and specificity for predicting persistent infection during the second stage of 2-stage revision, suggesting some combination of these diagnostic tests might be useful before reimplantation. No biomarker or culture accurately predicted treatment failure after reimplantation.
LEVEL OF EVIDENCE
Level III. See Instructions for Authors for a complete description of levels of evidence.
Topics: Humans; Interleukin-6; Persistent Infection; Arthroplasty; Replantation; Biomarkers; Diagnostic Tests, Routine; Prosthesis-Related Infections
PubMed: 36947634
DOI: 10.2106/JBJS.RVW.22.00201 -
Frontiers in Microbiology 2024The increasing demand for orthopedic surgeries, including joint replacements, is driven by an aging population and improved diagnosis of joint conditions. Orthopedic...
The increasing demand for orthopedic surgeries, including joint replacements, is driven by an aging population and improved diagnosis of joint conditions. Orthopedic surgeries carry a risk of infection, especially in patients with comorbidities. The rise of antibiotic resistance exacerbates this issue, necessitating alternatives like bioengineered antimicrobial peptides (AMPs), offering broad-spectrum activity and multiple action mechanisms. This review aimed to assess the prevalence of antimicrobial potential and the yield after purification among recombinant AMP families. The antimicrobial potential was evaluated using the Minimum Inhibitory Concentration (MIC) values against the most common bacteria involved in clinical infections. This systematic review adhered to PRISMA guidelines, focusing on studies of recombinant AMPs. The search strategy was run on PubMed, Scopus and Embase up to 30 March 2023. The Population, Exposure and Outcome model was used to extract the data from studies and ToxRTool for the risk of bias analysis. This review included studies providing peptide production yield data and MIC values against pathogenic bacteria. Non-English texts, reviews, conference abstracts, books, studies focusing solely on chemical synthesis, those reporting incomplete data sets, using non-standard MIC assessment methods, or presenting MIC values as ranges rather than precise concentrations, were excluded. From 370 publications, 34 studies on AMPs were analyzed. These covered 46 AMPs across 18 families, with Defensins and Hepcidins being most common. Yields varied from 0.5 to 2,700 mg/L. AMPs were tested against 23 bacterial genera, with MIC values ranging from 0.125 to >1,152 μg/mL. Arenicins showed the highest antimicrobial activity, particularly against common orthopedic infection pathogens. However, AMP production yields varied and some AMPs demonstrated limited effectiveness against certain bacterial strains. This systematic review emphasizes the critical role of bioengineered AMPs to cope infections and antibiotic resistance. It meticulously evaluates recombinant AMPs, focusing on their antimicrobial efficacy and production yields. The review highlights that, despite the variability in AMP yields and effectiveness, Arenicins and Defensins are promising candidates for future research and clinical applications in treating antibiotic-resistant orthopedic infections. This study contributes significantly to the understanding of AMPs in healthcare, underscoring their potential in addressing the growing challenge of antibiotic resistance. https://osf.io/2uq4c/.
PubMed: 38756724
DOI: 10.3389/fmicb.2024.1370826 -
Die Pharmazie Jul 2019Previous studies showed that gene polymorphisms may impact the development and progression of periodontitis; nevertheless, inconsistent conclusions were described. This... (Meta-Analysis)
Meta-Analysis
Previous studies showed that gene polymorphisms may impact the development and progression of periodontitis; nevertheless, inconsistent conclusions were described. This study meta-analytically explored the association between periodontitis the gene polymorphisms and periodontitis. We searched PubMed, Embase, Springer and Cochrane Library for the relevant case-control studies of periodontitis up to February 13, 2019. Two reviewers selected studies according to the predefined inclusion and exclusion criteria. Newcastle-Ottawa Scale (NOS) was used to assess the quality of studies, and the combined effect size was calculated using R 3.12 software. A total of 9 studies involving 4113 patients and 2373 controls were included. Meta-analysis of -G1654A gene polymorphisms showed that there were significant differences in model A G (OR = 3.7876, 95%CI = 2.9051-4.9382, < 0.001), AA GG (OR = 4.6743, 95%CI = 3.0900-7.0710, < 0.001), AA GG AG (OR = 3.5131, 95%CI = 2.4496-5.0384, < 0.001), AA + AG GG (OR = 4.3087, 95%CI = 2.8827-6.4402, < 0.001) and AG GG (OR = 3.0639, 95%CI = 1.6804-5.5863, = 0.003). However, no significant differences were found between rs11362, rs1799946 and rs1800972 and periodontitis. Sensitivity analysis implied that our results were robust and no publication bias was noticed. Our meta-analysis showed that the -G1654A polymorphism may be a genetic susceptibility factor for periodontitis.
Topics: Genetic Predisposition to Disease; Humans; Periodontitis; Polymorphism, Single Nucleotide; beta-Defensins
PubMed: 31288894
DOI: 10.1691/ph.2019.9459 -
BMC Medical Genetics Sep 2019Rotator cuff disease is a widespread musculoskeletal pathology and a major cause of shoulder pain. Studies on familial predisposition suggest that genetic plays a role... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Rotator cuff disease is a widespread musculoskeletal pathology and a major cause of shoulder pain. Studies on familial predisposition suggest that genetic plays a role in the pathogenesis of rotator cuff disease. Several genes are responsible for rotator cuff disease. The aim of this study was to perform a systematic review on genetic association between rotator cuff disease and genes variations.
METHODS
A systematic review of the literature was performed, in accordance with the PRISMA guidelines. PubMed, Medline, CINAHL, Cochrane, Embase and Google Scholar databases were searched comprehensively using the keywords: "Rotator cuff", "Gene", "Genetic", "Predisposition", "Single-nucleotide polymorphism" and "Genome-wide association".
RESULTS
8 studies investigating genes variations associated with rotator cuff tears were included in this review. 6 studies were case-control studies on candidate genes and 2 studies were GWASs. A significant association between SNPs and rotator cuff disease was found for DEFB1, FGFR1, FGFR3, ESRRB, FGF10, MMP-1, TNC, FCRL3, SASH1, SAP30BP, rs71404070 located next to cadherin8. Contradictory results were reported for MMP-3.
CONCLUSION
Further investigations are warranted to identify complete genetic profiles of rotator cuff disease and to clarify the complex interaction between genes, encoded proteins and environment. This may lead to individualized strategies for prevention and treatment of rotator cuff disease.
LEVEL OF EVIDENCE
Level IV, Systematic Review.
Topics: Cadherins; Databases, Factual; Fibroblast Growth Factor 10; Genetic Variation; Genome-Wide Association Study; Humans; Matrix Metalloproteinase 1; Nuclear Proteins; Polymorphism, Single Nucleotide; Receptor, Fibroblast Growth Factor, Type 1; Receptor, Fibroblast Growth Factor, Type 3; Receptors, Estrogen; Receptors, Immunologic; Rotator Cuff; Rotator Cuff Injuries; Tenascin; Transcription Factors; Tumor Suppressor Proteins; beta-Defensins
PubMed: 31477042
DOI: 10.1186/s12881-019-0883-y -
Digestion 2021The need for noninvasive markers of disease activity is mandatory in the assessment of Crohn's disease (CD). The most widely fecal biomarker in CD, despite several...
INTRODUCTION
The need for noninvasive markers of disease activity is mandatory in the assessment of Crohn's disease (CD). The most widely fecal biomarker in CD, despite several limits, is fecal calprotectin. This review aims to elucidate the role, if any, of all other fecal biomarkers, as alternative tools for assessing clinical and endoscopic disease activity, and predict capsule endoscopy findings, response to therapy, disease relapse, and postoperative recurrence. These fecal biomarkers included lactoferrin, S100A12, high mobility group box 1, neopterin, polymorphonuclear neutrophil elastase, fecal hemoglobin, alpha1-antitrypsin, lysozyme, human beta-defensin-2, neutrophil gelatinase-associated lipocalin, matrix metalloproteinase-9, chitinase 3-like-1, M2-pyruvate kinase, myeloperoxidase, and eosinophil proteins.
METHODS
A systematic electronic search in the medical literature was performed up to April 2020. Seventy eligible studies were identified out of 859 citations. Data were grouped according to the assessment of clinical and endoscopic disease activity, capsule endoscopy findings, response to therapy, prediction of relapse, and postoperative recurrence.
RESULTS
The overall correlation between lactoferrin and clinical indexes is poor, while performance is good with endoscopic scores. Lactoferrin seems to represent a reasonably good surrogate marker of response to therapy and to be potentially useful in identifying patients at high risk for endoscopic relapse or postoperative recurrence. The evaluation of the performance of all other fecal markers is limited by the lack of adequate data.
CONCLUSIONS
None of the fecal markers so far represents an acceptable alternative to calprotectin in clinical practice. Fecal lactoferrin is the only possible exception, but a more extensive investigation is still required.
Topics: Biomarkers; Crohn Disease; Feces; Humans; Lactoferrin; Leukocyte L1 Antigen Complex; Severity of Illness Index
PubMed: 34518458
DOI: 10.1159/000518419 -
Frontiers in Genetics 2019Chronic periodontitis (CP) is a growing problem that affects the worldwide population, having significant impacts on people's daily lives and economic development....
Chronic periodontitis (CP) is a growing problem that affects the worldwide population, having significant impacts on people's daily lives and economic development. Genetics is an important component in the determination of individual susceptibility to periodontal diseases. Numerous studies have been performed to investigate the association between beta defensin 1 () rs11362 polymorphism and risk of CP, but the results are still inconclusive. Therefore, we conducted this meta-analysis to ascertain whether this variation in is associated with CP susceptibility. The relevant studies were searched in PubMed and Chinese National Knowledge Infrastructure (CNKI) databases up to January 9, 2018. Two independent authors selected citations and extracted the data from eligible studies. Odds ratios (ORs) with their 95% confidence intervals (95% CIs) were used to assess the strength of the association. Seven case-control studies were included in this meta-analysis. Based on unadjusted data, there was no obvious association between rs11362 polymorphism and CP risk in all genetic models (A vs. G: OR = 0.86, 95%CI = 0.61-1.20; AA vs. GG: OR = 0.83, 95% CI = 00.50-1.39; AG vs. GG: OR = 1.01, 95%CI = 0.73-1.39; AG+AA vs. GG: OR = 0.91, 95% CI = 00.74-1.11; and AA vs. AG+GG: OR = 0.83, 95% CI = 00.57-1.21); the results of adjusted data also showed no significant relationship. Subgroup analyses based on ethnicity, participants' smoking status, HWE in controls and severity of CP all revealed similar results to that of the overall analysis. Sensitivity analysis indicated the results were robust and no evidence of publication bias was found. Our meta-analysis suggests that rs11362 polymorphism may not have an important effect on the risk of CP. Further large-scale and well-designed studies are necessary to validate our conclusion in the future.
PubMed: 30915104
DOI: 10.3389/fgene.2019.00179 -
Clinical Orthopaedics and Related... Jul 2018
PubMed: 29912808
DOI: 10.1097/CORR.0000000000000362