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Transplant International : Official... Oct 2020Several factors mediate intestinal microbiome (IM) alterations in transplant recipients, including immunosuppressive (IS) and antimicrobial drugs. Studies on the... (Review)
Review
Several factors mediate intestinal microbiome (IM) alterations in transplant recipients, including immunosuppressive (IS) and antimicrobial drugs. Studies on the structure and function of the IM in the post-transplant scenario and its role in the development of metabolic abnormalities, infection, and cancer are limited. We conducted a systematic review to study the taxonomic changes in liver (LT) and kidney (KT) transplantation, and their potential contribution to post-transplant complications. The review also includes pre-transplant taxa, which may play a critical role in microbial alterations post-transplant. Two reviewers independently screened articles, and assessed risk of bias. The review identified 13 clinical studies, which focused on adult kidney and liver transplant recipients. Patient characteristics and methodologies varied widely between studies. Ten studies reported increased an abundance of opportunistic pathogens (Enterobacteriaceae, Enterococcaceae, Fusobacteriaceae, and Streptococcaceae) followed by butyrate-producing bacteria (Lachnospiraceae and Ruminococcaceae) in nine studies in post-transplant conditions. The current evidence is mostly based on observational data and studies with no proof of causality. Therefore, further studies exploring the bacterial gene functions rather than taxonomic changes alone are in demand to better understand the potential contribution of the IM in post-transplant complications.
Topics: Adult; Dysbiosis; Humans; Immunosuppressive Agents; Kidney Transplantation; Liver; Transplant Recipients
PubMed: 32640109
DOI: 10.1111/tri.13696 -
Microbial Genomics Nov 2023(group B , GBS) has recently emerged as an important pathogen among adults. However, it is overlooked in this population, with all global efforts being directed towards...
(group B , GBS) has recently emerged as an important pathogen among adults. However, it is overlooked in this population, with all global efforts being directed towards its containment among pregnant women and neonates. This systematic review assessed the molecular epidemiology and compared how the lineages circulating among non-pregnant populations relate to those of pregnant and neonatal populations worldwide. A systematic search was performed across nine databases from 1 January 2000 up to and including 20 September 2021, with no language restrictions. The Joanna Briggs Institute (JBI) Prevalence Critical Appraisal Tool (PCAT) was used to assess the quality of included studies. The global population structure of GBS from the non-pregnant population was analysed using typing and phylogenetic reconstruction tools. Twenty-four articles out of 13 509 retrieved across 9 databases were eligible. Most studies were conducted in the World Health Organization European region (12/24, 50 %), followed by the Western Pacific region (6/24, 25 %) and the Americas region (6/24, 25 %). Serotype V (23%, 2310/10240) and clonal complex (CC) 1 (29 %, 2157/7470) were the most frequent serotype and CC, respectively. The pilus island PI1 : PI2A combination (29 %, 3931/13751) was the most prevalent surface protein gene, while the tetracycline resistance M (55 %, 5892/10624) was the leading antibiotic resistance gene. This study highlights that, given the common serotype distribution identified among non-pregnant populations (V, III, Ia, Ib, II and IV), vaccines including these six serotypes will provide broad coverage. The study indicates advanced molecular epidemiology studies, especially in resource-constrained settings for evidence-based decisions. Finally, the study shows that considering all at-risk populations in an inclusive approach is essential to ensure the sustainable containment of GBS.
Topics: Pregnancy; Adult; Infant, Newborn; Humans; Female; Streptococcus agalactiae; Molecular Epidemiology; Phylogeny; Anti-Bacterial Agents; Databases, Factual
PubMed: 38019122
DOI: 10.1099/mgen.0.001140 -
Dermatology (Basel, Switzerland) 2021Acne inversa/hidradenitis suppurativa (HS) is a chronic, recurrent inflammatory disease of the skin that can significantly affect patients' quality of life. The etiology...
BACKGROUND
Acne inversa/hidradenitis suppurativa (HS) is a chronic, recurrent inflammatory disease of the skin that can significantly affect patients' quality of life. The etiology and pathogenesis of HS are unclear and gene mutations might play a role.
SUMMARY
The primary focus of the review is on aggregating the gene mutations reported, summarizing the structure of γ-secretase and analyzing and speculating about the mechanism and the underlying relations between gene mutation and functional changes of protein. The systematic literature review was done by searching the PubMed, Embase, and Web of Science databases. γ-Secretase is an intramembrane protease complex responsible for the intramembranous cleavage of more than 30 type-1 transmembrane proteins including amyloid precursor protein and Notch receptors. The protein complex consists of four hydrophobic proteins: presenilin, presenilin enhancer-2 (PSENEN), nicastrin, and anterior pharynx defective 1 (APH1). To date, 57 mutations of γ-secretase genes have been reported in 70 patients or families worldwide, including 39 in NCSTN, 14 in PSENEN, and 4 in PSEN1, of which 17 are frameshifts, 15 result in nonsense mutations, 13 in missense mutations, and 12 are splice site mutations. Given the structure of γ-secretase and analysis of related mutation loci of NCSTN, PSENEN, and PSEN1, mutations in γ-secretase genes could affect activation of presenilin, prevent substrate binding, and hinder intramembrane cleavage of select proteins.
Topics: Amyloid Precursor Protein Secretases; Hidradenitis Suppurativa; Humans; Mutation
PubMed: 33333507
DOI: 10.1159/000512455 -
The Journal of Pain 2020Chronic postsurgical pain (CPSP) is a significant detriment to postsurgical recovery and a risk factor for prolonged opioid use. Emerging evidence suggests the estimated... (Meta-Analysis)
Meta-Analysis
Chronic postsurgical pain (CPSP) is a significant detriment to postsurgical recovery and a risk factor for prolonged opioid use. Emerging evidence suggests the estimated heritability for chronic pain is 45% and that genetic factors partially explain individual susceptibility to CPSP. The aim of this study was to systematically review, assess quality, and summarize the studies in humans that have investigated genetic factors associated with CPSP. We also conducted a meta-analysis to derive a single effect size for evaluable genetic associations with CPSP. Our comprehensive literature search included review of 21 full-text articles evaluating variants of 69 genes for association with CPSP. We found significant gene variant associations reported for variants/haplotypes of 26 genes involved in neurotransmission, pain signaling, immune responses and neuroactive ligand-receptor interaction, with CPSP. Six variants of 5 genes (COMT: rs4680 and rs6269, OPRM1: rs1799971, GCH1: rs3783641, KCNS1: rs734784 and TNFA: rs1800629), were evaluated by more than one study and were included in the meta-analysis. At rs734784 (A>G) of KCNS1, presence of G allele marginally increased risk of CPSP (Additive genetic model; Odds ratio: 1.511; 95% CI 1-2.284; P value: .050), while the other variants did not withstand meta-analyses criteria. Our findings demonstrate the role of genetic factors with different functions in CPSP, and also emphasize that single genetic factors have small effect sizes in explaining complex conditions like CPSP. Heterogeneity in surgical cohorts, population structure, and outcome definitions, as well as small number of available studies evaluating same variants, limit the meta-analysis. There is a need for large-scale, homogenous, replication studies to validate candidate genes, and understand the underlying biological networks underpinning CPSP. PERSPECTIVE: Our systematic review comprehensively describes 21 studies evaluating genetic association with CPSP, and limitations thereof. A meta-analysis of 6 variants (5 genes) found marginally increased risk for CPSP associated with rs734784 A>G of the potassium voltage-gated channel gene (KCNS1). Understanding genetic predisposition for CPSP will enable prediction and personalized management.
Topics: Genetic Predisposition to Disease; Humans; Pain, Postoperative
PubMed: 31129315
DOI: 10.1016/j.jpain.2019.05.008 -
The Lancet. Microbe Feb 2024Clinical bedaquiline resistance predominantly involves mutations in mmpR5 (Rv0678). However, mmpR5 resistance-associated variants (RAVs) have a variable relationship... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Clinical bedaquiline resistance predominantly involves mutations in mmpR5 (Rv0678). However, mmpR5 resistance-associated variants (RAVs) have a variable relationship with phenotypic Mycobacterium tuberculosis resistance. We did a systematic review to assess the maximal sensitivity of sequencing bedaquiline resistance-associated genes and evaluate the association between RAVs and phenotypic resistance, using traditional and machine-based learning techniques.
METHODS
We screened public databases for articles published from database inception until Oct 31, 2022. Eligible studies performed sequencing of at least mmpR5 and atpE on clinically sourced M tuberculosis isolates and measured bedaquiline minimum inhibitory concentrations (MICs). A bias risk scoring tool was used to identify bias. Individual genetic mutations and corresponding MICs were aggregated, and odds ratios calculated to determine association of mutations with resistance. Machine-based learning methods were used to define test characteristics of parsimonious sets of diagnostic RAVs, and mmpR5 mutations were mapped to the protein structure to highlight mechanisms of resistance. This study was registered in the PROSPERO database (CRD42022346547).
FINDINGS
18 eligible studies were identified, comprising 975 M tuberculosis isolates containing at least one potential RAV (mutation in mmpR5, atpE, atpB, or pepQ), with 201 (20·6%) showing phenotypic bedaquiline resistance. 84 (29·5%) of 285 resistant isolates had no candidate gene mutation. Sensitivity and positive predictive value of taking an any mutation approach was 69% and 14%, respectively. 13 mutations, all in mmpR5, had a significant association with a resistant MIC (adjusted p<0·05). Gradient-boosted machine classifier models for predicting intermediate or resistant and resistant phenotypes both had receiver operator characteristic c statistic of 0·73 (95% CI 0·70-0·76). Frameshift mutations clustered in the α1 helix DNA-binding domain, and substitutions in the α2 and α3 helix hinge region and in the α4 helix-binding domain.
INTERPRETATION
Sequencing candidate genes is insufficiently sensitive to diagnose clinical bedaquiline resistance, but where identified, some mutations should be assumed to be associated with resistance. Genomic tools are most likely to be effective in combination with rapid phenotypic diagnostics. This study was limited by selective sampling in contributing studies and only considering single genetic loci as causative of resistance.
FUNDING
Francis Crick Institute and National Institute of Allergy and Infectious Diseases at the National Institutes of Health.
Topics: United States; Humans; Antitubercular Agents; Diarylquinolines; Tuberculosis; Mycobacterium tuberculosis; Genomics
PubMed: 38215766
DOI: 10.1016/S2666-5247(23)00317-8 -
Reproductive Biology and Endocrinology... Aug 2017The Catsper channel is a sperm-specific, Ca-permeable, pH-dependent, and low voltage-dependent channel that is essential for the hyperactivity of sperm flagellum,... (Review)
Review
The Catsper channel is a sperm-specific, Ca-permeable, pH-dependent, and low voltage-dependent channel that is essential for the hyperactivity of sperm flagellum, chemotaxis towards the egg, capacitation and acrosome reaction. All of these physiological events require calcium entry into sperm cells. Remarkably, Catsper genes are exclusively expressed in the testis during spermatogenesis, and are sensitive to ion channel-induced pH change, such as NHEs, CaATPase, K channel, Hv1 channel and HCO transporters. Furthermore, the Catsper channel is regulated by some physiological stimulants, such as progesterone, cyclic nucleotides (e.g., cAMP, cGMP), zona pellucida (ZP) glycoproteins and bovine serum albumin (BSA). All of these factors normally stimulate Ca entry into sperm through the Catsper channel. In addition, the Catsper channel may be a potential target for male infertility treatment or contraception. This review will focus on the structure, functions, regulation mechanisms and medicinal targets of the Catsper channel.
Topics: Animals; Calcium Channels; Calcium Signaling; Humans; Hydrogen-Ion Concentration; Infertility, Male; Male; Mice; Spermatozoa
PubMed: 28810916
DOI: 10.1186/s12958-017-0281-2 -
Frontiers in Pharmacology 2023Irritable bowel syndrome (IBS) is a group of functional intestinal disorders characterized by abdominal pain, bloating, and changes in bowel habits, and/or stool...
Irritable bowel syndrome (IBS) is a group of functional intestinal disorders characterized by abdominal pain, bloating, and changes in bowel habits, and/or stool characteristics. Recent studies have shown that there has been a significant advancement in the study of visceral hypersensitivity in IBS. Through the use of bibliometrics, this study aims to provide a comprehensive overview of the knowledge structure and research hotpots of visceral hypersensitivity in IBS. Publications related to visceral hypersensitivity in IBS from 2012 to 2022 were searched on the web of science core collection (WoSCC) database. CiteSpace.6.1. R2 and Vosviewer 1.6.17 were used to perform bibliometric analysis. A total of 974 articles led by China and the United States from 52 countries were included. Over the past decade, the number of articles on visceral hypersensitivity and IBS has steadily increased year by year. China, the United States, and Belgium are the main countries in this field. Univ Oklahoma, Univ Gothenburg, and Zhejiang University are the main research institutions. Simren, Magnus, Greenwood-van meerveld, Beverley, and Tack, Jan are the most published authors in this research field. The research on the causes, genes, and pathways involved in visceral hypersensitivity in IBS and the mechanism of IBS are the main topics and hotspots in this field. This study also found that gut microbiota may be related to the occurrence of visceral hypersensitivity, and probiotics may be a new method for the treatment of visceral hypersensitivity and pain, which may become a new direction for research in this field. This is the first bibliometric study to comprehensively summarize the research trends and developments of visceral hypersensitivity in IBS. This information provides the research frontier and hot topics in this field in recent years, which will provide a reference for scholars studying this field.
PubMed: 37201020
DOI: 10.3389/fphar.2023.1175057 -
NeuroImage. Clinical 2020Diffusion magnetic resonance imaging (dMRI) is an imaging technique which probes the random motion of water molecules in tissues and has been widely applied to... (Review)
Review
Diffusion magnetic resonance imaging (dMRI) is an imaging technique which probes the random motion of water molecules in tissues and has been widely applied to investigate changes in white matter microstructure in Alzheimer's Disease. This paper aims to systematically review studies that examined the effect of Alzheimer's risk genes on white matter microstructure. We assimilated findings from 37 studies and reviewed their diffusion pre-processing and analysis methods. Most studies estimate the diffusion tensor (DT) and compare derived quantitative measures such as fractional anisotropy and mean diffusivity between groups. Those with increased AD genetic risk are associated with reduced anisotropy and increased diffusivity across the brain, most notably the temporal and frontal lobes, cingulum and corpus callosum. Structural abnormalities are most evident amongst those with established Alzheimer's Disease. Recent studies employ signal representations and analysis frameworks beyond DT MRI but show that dMRI overall lacks specificity to disease pathology. However, as the field advances, these techniques may prove useful in pre-symptomatic diagnosis or staging of Alzheimer's disease.
Topics: Alzheimer Disease; Anisotropy; Brain; Diffusion Magnetic Resonance Imaging; Diffusion Tensor Imaging; Humans; White Matter
PubMed: 32758801
DOI: 10.1016/j.nicl.2020.102359 -
Medicine Sep 2017Matrix metalloproteinases (MMPs), particularly gelatinase A (MMP-2) and gelatinase B (MMP-9), as well as their tissue inhibitors (TIMP-1 and TIMP-2), are involved in the... (Review)
Review
BACKGROUND
Matrix metalloproteinases (MMPs), particularly gelatinase A (MMP-2) and gelatinase B (MMP-9), as well as their tissue inhibitors (TIMP-1 and TIMP-2), are involved in the development of skeletal muscle tissue, in the repair process after muscle injury and in the adaptive modifications induced by physical exercise in skeletal muscle. This paper aims at reviewing results from human studies that investigated the role of gelatinases and their inhibitors in skeletal muscle response to acute physical exercise or training.
METHODS
Electronic databases PubMed/MEDLINE, Scopus and Web of Science were searched for papers published between January 2000 and February 2017. The papers were eligible when reporting human studies in which MMP-2 and/or MMP-9 and/or the inhibitors TIMP-1/TIMP-2 were evaluated, in blood or muscular tissue, before and after acute physical exercise or before and after a period of structured physical training. We included studies on healthy subjects and patients with chronic metabolic diseases (obesity, diabetes mellitus, metabolic syndrome-MS) or asymptomatic coronary artery disease. We excluded studies on patients with neurological, rheumatologic or neoplastic diseases.
RESULTS
Studies conducted on muscle biopsies showed an early stimulation of MMP-9 gene transcription as a result of acute exercise, whereas MMP-2 and TIMP transcription resulted from regular repetition of exercise over time. Studies on serum or plasma level of gelatinases and their inhibitors showed an early release of MMP-9 after acute exercise of sufficient intensity, while data on MMP-2 and TIMP were more contrasting. Most of the studies dealing with the effect of training indicated a trend toward reduction in blood gelatinase levels, once again more clear for MMP-9. This result was related to an anti-inflammatory effect of regular exercise and was more evident when training consisted of aerobic activities. This study has limitations: as the initial selection was done through titles and abstracts, incomplete retrieval cannot be excluded, as well as we cannot exclude bias due to selective reporting within studies.
CONCLUSION
A better knowledge of the molecular events activated by different types of acute exercise and regular training could be of great relevance in order to maximize the benefits of physical activity in healthy subjects and patients.
Topics: Exercise; Gelatinases; Humans; Muscle, Skeletal
PubMed: 28906407
DOI: 10.1097/MD.0000000000008072 -
Journal of the Royal Society, Interface May 2023Contact structure among livestock populations influences the transmission of infectious agents among them. Models simulating realistic contact networks therefore have... (Review)
Review
Contact structure among livestock populations influences the transmission of infectious agents among them. Models simulating realistic contact networks therefore have important applications for generating insights relevant to livestock diseases. This systematic review identifies and compares such models, their applications, data sources and how their validity was assessed. From 52 publications, 37 models were identified comprising seven model frameworks. These included mathematical models ( = 8; including generalized random graphs, scale-free, Watts-Strogatz and spatial models), agent-based models ( = 8), radiation models ( = 1) (collectively, considered 'mechanistic'), gravity models ( = 4), exponential random graph models ( = 9), other forms of statistical model ( = 6) (statistical) and random forests ( = 1) (machine learning). Overall, nearly half of the models were used as inputs for network-based epidemiological models. In all models, edges represented livestock movements, sometimes alongside other forms of contact. Statistical models were often applied to infer factors associated with network formation ( = 12). Mechanistic models were commonly applied to assess the interaction between network structure and disease dissemination ( = 6). Mechanistic, statistical and machine learning models were all applied to generate networks given limited data ( = 13). There was considerable variation in the approaches used for model validation. Finally, we discuss the relative strengths and weaknesses of model frameworks in different use cases.
Topics: Animals; Livestock; Models, Theoretical; Models, Statistical; Movement
PubMed: 37194271
DOI: 10.1098/rsif.2022.0890