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Molecular Metabolism Nov 2023The gut microbiota is increasingly recognized as a crucial factor in human health and disease. Metformin, a commonly prescribed medication for type 2 diabetes, has been... (Review)
Review
BACKGROUND
The gut microbiota is increasingly recognized as a crucial factor in human health and disease. Metformin, a commonly prescribed medication for type 2 diabetes, has been studied for its potential impact on the gut microbiota in preclinical models. However, the effects of metformin on the gut microbiota in humans remain uncertain.
SCOPE OF REVIEW
We conducted a systematic review of clinical trials and observational studies to assess the existing knowledge on the impact of metformin on the gut microbiota in humans. The review focused on changes in bacterial composition and diversity following metformin treatment.
MAJOR CONCLUSIONS
Thirteen studies were included in the analysis. The results revealed alterations in the abundance of bacterial genera from various phyla, suggesting that metformin may selectively influence certain groups of bacteria in the gut microbiota. However, the effects on gut microbiota diversity were inconsistent across populations, with conflicting findings on changes in alpha and beta diversity measures. Overall, the use of metformin was associated with changes in the abundance of specific bacterial genera within the gut microbiota of human populations. However, the effects on gut microbiota diversity were not consistent, highlighting the need for further research to understand the underlying mechanisms and clinical significance of these changes.
Topics: Humans; Metformin; Diabetes Mellitus, Type 2; Gastrointestinal Microbiome; Bacteria
PubMed: 37696355
DOI: 10.1016/j.molmet.2023.101805 -
World Journal of Gastroenterology Mar 2016To construct a global "metabolic phenotype" of pancreatic ductal adenocarcinoma (PDAC) reflecting tumour-related metabolic enzyme expression. (Review)
Review
AIM
To construct a global "metabolic phenotype" of pancreatic ductal adenocarcinoma (PDAC) reflecting tumour-related metabolic enzyme expression.
METHODS
A systematic review of the literature was performed using OvidSP and PubMed databases using keywords "pancreatic cancer" and individual glycolytic and mitochondrial oxidative phosphorylation (MOP) enzymes. Both human and animal studies investigating the oncological effect of enzyme expression changes and inhibitors in both an in vitro and in vivo setting were included in the review. Data reporting changes in enzyme expression and the effects on PDAC cells, such as survival and metastatic potential, were extracted to construct a metabolic phenotype.
RESULTS
Seven hundred and ten papers were initially retrieved, and were screened to meet the review inclusion criteria. 107 unique articles were identified as reporting data involving glycolytic enzymes, and 28 articles involving MOP enzymes in PDAC. Data extraction followed a pre-defined protocol. There is consistent over-expression of glycolytic enzymes and lactate dehydrogenase in keeping with the Warburg effect to facilitate rapid adenosine-triphosphate production from glycolysis. Certain isoforms of these enzymes were over-expressed specifically in PDAC. Altering expression levels of HK, PGI, FBA, enolase, PK-M2 and LDA-A with metabolic inhibitors have shown a favourable effect on PDAC, thus identifying these as potential therapeutic targets. However, the Warburg effect on MOP enzymes is less clear, with different expression levels at different points in the Krebs cycle resulting in a fundamental change of metabolite levels, suggesting that other essential anabolic pathways are being stimulated.
CONCLUSION
Further characterisation of the PDAC metabolic phenotype is necessary as currently there are few clinical studies and no successful clinical trials targeting metabolic enzymes.
Topics: Animals; Carcinoma, Pancreatic Ductal; Energy Metabolism; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Glucose; Humans; Pancreatic Neoplasms; Phenotype
PubMed: 27022229
DOI: 10.3748/wjg.v22.i12.3471 -
Journal of Psychiatric Research Nov 2020Although the precise pathophysiologies underlying autism spectrum disorder (ASD) has not yet been fully clarified, growing evidence supports the involvement of... (Review)
Review
BACKGROUND
Although the precise pathophysiologies underlying autism spectrum disorder (ASD) has not yet been fully clarified, growing evidence supports the involvement of neuroinflammation in the pathogenesis of this disorder, with microglia being particular relevance in the pathophysiologic processes.
OBJECTIVE
The present review aimed to systematically characterize existing literature regarding the role of microglia mediated neuroinflammation in the etiology of ASD.
METHODS
A systematic search was conducted for records indexed within Pubmed, EMBASE, or Web of Science to identify potentially eligible publications. Study selection and data extraction were performed by two authors, and the discrepancies in each step were settled through discussions.
RESULTS
A total of 14 studies comprising 1007 subjects met the eligibility criteria for this review, including 8 immunohistochemistry (IHC) studies, 5 genetic analysis studies, and 1 positron emission tomography (PET) studies. Although small in quantity, the included studies collectively pointed to a role of microglia mediated neuroinflammation in the pathogenesis of ASD.
CONCLUSION
Findings generated from this review consistently supported the involvement of neuroinflammation in the development of ASD, confirmed by the activation of microglia in different brain regions, involving increased cell number or cell density, morphological alterations, and phenotypic shifts.
Topics: Autism Spectrum Disorder; Brain; Humans; Inflammation; Microglia; Positron-Emission Tomography
PubMed: 32823050
DOI: 10.1016/j.jpsychires.2020.07.013 -
Current Opinion in Neurology Jun 2017To present an updated and streamlined overview of the metabolic and biochemical aspect of the migraine pathophysiology based on findings from phosphorous (P) and... (Meta-Analysis)
Meta-Analysis Review
PURPOSE OF REVIEW
To present an updated and streamlined overview of the metabolic and biochemical aspect of the migraine pathophysiology based on findings from phosphorous (P) and hydrogen (H) magnetic resonance spectroscopy (MRS) studies.
RECENT FINDINGS
Despite of the variation in the methodology and quality of the MRS migraine studies over time, some results were consistent and reproducible. P-MRS studies suggested reduced availability of neuronal energy and implied a mitochondrial dysfunction in the migraine brain. H-MRS studies reported interictal abnormalities in the excitatory and inhibitory neurotransmitters, glutamate and γ-aminobutyric acid (GABA), suggesting persistent altered excitability in migraine patients. N-Acetylaspartate levels were decreased in migraine, probably due to a mitochondrial dysfunction and abnormal energy metabolism. The reported abnormalities may increase the susceptibility of migraine patients to excitatory stimulation, such as migraine attack triggers.
SUMMARY
Several biochemical aspects of the migraine pathophysiology remain to be elucidated using MRS, such as the migraine attack, correlation to disease severity, and medication efficacy. Nevertheless, to identify a biomarker in migraine, MRS may be a valuable noninvasive technique.
Topics: Aspartic Acid; Biomarkers; Humans; Magnetic Resonance Spectroscopy; Migraine Disorders; gamma-Aminobutyric Acid
PubMed: 28240609
DOI: 10.1097/WCO.0000000000000436 -
Journal of Leukocyte Biology May 2022Inflammation is a key driver of common noncommunicable diseases. Among common triggers of inflammation, chronic gingival inflammation (periodontitis) triggers a... (Meta-Analysis)
Meta-Analysis Review
Inflammation is a key driver of common noncommunicable diseases. Among common triggers of inflammation, chronic gingival inflammation (periodontitis) triggers a consistent humoral host inflammatory response, but little is known on its impact on circulating inflammatory cell profiles. We aimed to systematically appraise all the evidence linking periodontitis and its treatment to circulating inflammatory cell profiles. From 6 databases, 157 studies were eligible for qualitative synthesis and 29 studies for meta-analysis. Our meta-analysis showed that participants with periodontitis exhibited a significant mean increase in circulating CD4 , CD4 CD45RO , IFNγ-expressing CD4 and CD8 T cells, CD19 CD27 and CD5 B cells, CD14 CD16 monocytes, and CD16 neutrophils but decrease in CD8 T and CD14 CD16 monocytes. Our qualitative synthesis revealed that peripheral blood neutrophils of patients with periodontitis consistently showed elevated production of reactive oxygen species (ROS) when compared with those of healthy controls. Some evidence suggested that the treatment of periodontitis reversed the exaggerated ROS production, but limited and inconclusive data were found on several circulating inflammatory cell profiling. We conclude that periodontitis and its treatment are associated with minor but consistent alterations in circulating inflammatory cell profiles. These changes could represent key mechanisms explaining the association of periodontitis with other comorbidities such as cardiovascular disease, diabetes, and rheumatoid arthritis.
Topics: CD8-Positive T-Lymphocytes; Humans; Inflammation; Monocytes; Periodontitis; Reactive Oxygen Species
PubMed: 35199874
DOI: 10.1002/JLB.5RU1021-524R -
Chemosphere Oct 2023Glyphosate was classified as a probable human carcinogen (Group 2A) by the International Agency for Research on Cancer (IARC) partially due to strong mechanistic... (Review)
Review
Glyphosate was classified as a probable human carcinogen (Group 2A) by the International Agency for Research on Cancer (IARC) partially due to strong mechanistic evidence in 2015. Since then, numerous studies of glyphosate and its formulations (GBF) have emerged. These studies can be evaluated for cancer hazard identification with the newly described ten key characteristics (KC) of carcinogens approach. Our objective was to assess all in vivo, ex vivo, and in vitro mechanistic studies of human and experimental animals (mammals) that compared exposure to glyphosate/GBF with low/no exposure counterparts for evidence of the ten KCs. A protocol with our methods adhering to PRISMA guidelines was registered a priori (INPLASY202180045). Two blinded reviewers screened all in vivo, ex vivo, and in vitro studies of glyphosate/GBF exposure in humans/mammals reporting any KC-related outcome available in PubMed before August 2021. Studies that met inclusion criteria underwent data extraction conducted in duplicate for each KC outcome reported along with key aspects of internal/external validity, results, and reference information. These data were used to construct a matrix that was subsequently analyzed in the program R to conduct strength of evidence and quality assessments. Of the 2537 articles screened, 175 articles met inclusion criteria, from which we extracted >50,000 data points related to KC outcomes. Data analysis revealed strong evidence for KC2, KC4, KC5, KC6, KC8, limited evidence for KC1 and KC3, and inadequate evidence for KC7, KC9, and KC10. Notably, our in-depth quality analyses of genotoxicity (KC2) and endocrine disruption (KC8) revealed strong and consistent positive findings. For KC2, we found: 1) studies conducted in humans and human cells provided stronger positive evidence than counterpart animal models; 2) GBF elicited a stronger effect in both human and animal systems when compared to glyphosate alone; and 3) the highest quality studies in humans and human cells consistently revealed strong evidence of genotoxicity. Our analysis of KC8 indicated that glyphosate's ability to modulate hormone levels and estrogen receptor activity is sensitive to both exposure concentration and formulation. The modulations observed provide clear evidence that glyphosate interacts with receptors, alters receptor activation, and modulates the levels and effects of endogenous ligands (including hormones). Our findings strengthen the mechanistic evidence that glyphosate is a probable human carcinogen and provide biological plausibility for previously reported cancer associations in humans, such as non-Hodgkin lymphoma. We identified potential molecular interactions and subsequent key events that were used to generate a probable pathway to lymphomagenesis.
Topics: Animals; Humans; Carcinogens; Herbicides; Neoplasms; Lymphoma, Non-Hodgkin; Mammals; Glyphosate
PubMed: 37474029
DOI: 10.1016/j.chemosphere.2023.139572 -
Frontiers in Genetics 2021Huntington's disease (HD) is a chronic neurodegenerative disorder caused by an expansion of polyglutamine repeats in exon 1 of the Huntingtin gene. Transcriptional... (Review)
Review
Huntington's disease (HD) is a chronic neurodegenerative disorder caused by an expansion of polyglutamine repeats in exon 1 of the Huntingtin gene. Transcriptional dysregulation accompanied by epigenetic alterations is an early and central disease mechanism in HD yet, the exact mechanisms and regulators, and their associated gene expression programs remain incompletely understood. This systematic review investigates genome-wide transcriptional studies that were conducted using RNA sequencing (RNA-seq) technology in HD patients and models. The review protocol was registered at the Open Science Framework (OSF). The biomedical literature and gene expression databases, PubMed and NCBI BioProject, Array Express, European Nucleotide Archive (ENA), European Genome-Phenome Archive (EGA), respectively, were searched using the defined terms specified in the protocol following the PRISMA guidelines. We conducted a complete literature and database search to retrieve all RNA-seq-based gene expression studies in HD published until August 2020, retrieving 288 articles and 237 datasets from PubMed and the databases, respectively. A total of 27 studies meeting the eligibility criteria were included in this review. Collectively, comparative analysis of the datasets revealed frequent genes that are consistently dysregulated in HD. In postmortem brains from HD patients, and genes were commonly upregulated across all brain regions and cell types except for medium spiny neurons (MSNs) at symptomatic disease stage, and and genes were altered in expression in all symptomatic brain datasets, indicating early and sustained changes in the expression of genes related to heat shock response as well as response to misfolded proteins. Specifically in indirect pathway medium spiny neurons (iMSNs), mitochondria related genes were among the top uniquely dysregulated genes. Interestingly, blood from HD patients showed commonly differentially expressed genes with a number of brain regions and cells, with the highest number of overlapping genes with MSNs and BA9 region at symptomatic stage. We also found the differential expression and predicted altered activity of a set of transcription factors and epigenetic regulators, including and , respectively, which may underlie the observed transcriptional changes in HD. Altogether, our work provides a complete overview of the transcriptional studies in HD, and by data synthesis, reveals a number of common and unique gene expression and regulatory changes across different cell and tissue types in HD. These changes could elucidate new insights into molecular mechanisms of differential vulnerability in HD. https://osf.io/pm3wq.
PubMed: 34721539
DOI: 10.3389/fgene.2021.751033 -
Expert Review of Respiratory Medicine Jan 2018Palivizumab is a humanized monoclonal antibody used for respiratory syncytial virus (RSV) prophylaxis. RSV is the primary cause of lower respiratory tract infection in... (Review)
Review
Palivizumab is a humanized monoclonal antibody used for respiratory syncytial virus (RSV) prophylaxis. RSV is the primary cause of lower respiratory tract infection in children aged <2 years, and can give rise to high-burden hospitalization and respiratory complications in later life. Adherence to a monthly dosing regimen, both in timing and injection number, is essential to sustain therapeutic levels of palivizumab and maintain protective status. Deviation from the approved dosing schedule may reduce the efficacy of palivizumab and increase the risk of breakthrough RSV infection and hospitalization. Areas covered: There is no standardized definition of adherence to palivizumab treatment. This review addresses the wide variability in defining and reporting adherence to palivizumab prophylaxis across different studies. The review assesses whether a relationship exists in the outcomes reported in studies relative to the monthly adherence protocol as defined in published randomized controlled trials of the efficacy and safety of palivizumab. Expert commentary: Standardized detailed reporting of adherence to palivizumab prophylaxis using consistent definitions will help provide a more robust level of evidence. This information may be important when considering variations in effectiveness, alterations to recommendations and guidelines, and cost-effectiveness of treatment.
Topics: Antiviral Agents; Cost-Benefit Analysis; Humans; Infant; Infant, Newborn; Palivizumab; Respiratory Syncytial Virus Infections; Treatment Outcome
PubMed: 29130355
DOI: 10.1080/17476348.2018.1401926 -
Oncotarget Nov 2019To assess the association of tumor mutational burden (TMB) with clinical outcomes, other biomarkers and patient/disease characteristics in patients receiving therapy... (Review)
Review
To assess the association of tumor mutational burden (TMB) with clinical outcomes, other biomarkers and patient/disease characteristics in patients receiving therapy for lung cancer. In total, 4,303 publications were identified; 81 publications were included. The majority of publications assessing clinical efficacy of immunotherapy reported an association with high TMB, particularly when assessing progression-free survival and objective response rate. High TMB was consistently associated with alterations, and negatively associated with EGFR mutations. High TMB was also associated with smoking, squamous cell non-small cell lung carcinoma, and being male. A systematic literature review based upon an a priori protocol was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Cochrane methodologies. Searches were conducted in EMBASE, SCOPUS, Ovid MEDLINE, and Emcare (from January 2012 until April 2018) and in two clinical trial registries. Conference abstracts were identified in EMBASE, and in targeted searches of recent major conference proceedings (from January 2016 until April 2018). Publications reporting data in patients receiving therapy for lung cancer that reported TMB and its association with clinical efficacy, or with other biomarkers or patient/disease characteristics, were included. Results are presented descriptively. This systematic literature review identified several clinical outcomes, biomarkers, and patient/disease characteristics associated with high TMB, and highlights the need for standardized definitions and testing practices. Further studies using standardized methodology are required to inform treatment decisions.
PubMed: 31762941
DOI: 10.18632/oncotarget.27287 -
Frontiers in Immunology 2023The aim of this systematic review was to summarize the available literature on gut microbiome (GMB) and osteoarthritis (OA), analyze the correlation between GMB and OA,...
OBJECTIVES
The aim of this systematic review was to summarize the available literature on gut microbiome (GMB) and osteoarthritis (OA), analyze the correlation between GMB and OA, and explore potential underlying mechanisms.
METHODS
A systematic search of the PubMed, Embase, Cochrane, and Web of Science with the keywords "Gut Microbiome" and "Osteoarthritis" was conducted to identify the human and animal studies exploring the association between GMB and OA. The retrieval time range was from the database inception to July 31, 2022. Studies reported the other arthritic diseases without OA, reviews, and studies focused on the microbiome in other parts of the body with OA, such as oral or skin, were excluded. The included studies were mainly reviewed for GMB composition, OA severity, inflammatory factors, and intestinal permeability.
RESULTS
There were 31 studies published met the inclusion criteria and were analyzed, including 10 human studies and 21 animal studies. Human and animal studies have reached a consistent conclusion that GMB dysbiosis could aggravate OA. In addition, several studies have found that alterations of GMB composition can increase intestinal permeability and serum levels of inflammatory factors, while regulating GMB can alleviate the changes. Owing to the susceptibility of GMB to internal and external environments, genetics, and geography, the included studies were not consistent in GMB composition analysis.
CONCLUSION
There is a lack of high-quality studies evaluating the effects of GMB on OA. Available evidence indicated that GMB dysbiosis aggravated OA through activating the immune response and subsequent induction of inflammation. Future studies should focus on more prospective, cohort studies combined with multi-omics to further clarify the correlation.
Topics: Animals; Humans; Dysbiosis; Prospective Studies; Osteoarthritis; Inflammation; Gastrointestinal Microbiome
PubMed: 37180142
DOI: 10.3389/fimmu.2023.1150572