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International Journal of Molecular... Jul 2023Temporal lobe epilepsy (TLE) is the most common form of epilepsy in adults. Tissue reorganization at the site of the epileptogenic focus is accompanied by changes in the... (Review)
Review
Temporal lobe epilepsy (TLE) is the most common form of epilepsy in adults. Tissue reorganization at the site of the epileptogenic focus is accompanied by changes in the expression patterns of protein molecules. The study of mRNA and its corresponding proteins is crucial for understanding the pathogenesis of the disease. Protein expression profiles do not always directly correlate with the levels of their transcripts; therefore, it is protein profiling that is no less important for understanding the molecular mechanisms and biological processes of TLE. The study and annotation of proteins that are statistically significantly different in patients with TLE is an approach to search for biomarkers of this disease, various stages of its development, as well as a method for searching for specific targets for the development of a further therapeutic strategy. When writing a systematic review, the following aggregators of scientific journals were used: MDPI, PubMed, ScienceDirect, Springer, and Web of Science. Scientific articles were searched using the following keywords: "proteomic", "mass-spectrometry", "protein expression", "temporal lobe epilepsy", and "biomarkers". Publications from 2003 to the present have been analyzed. Studies of brain tissues, experimental models of epilepsy, as well as biological fluids, were analyzed. For each of the groups, aberrantly expressed proteins found in various studies were isolated. Most of the studies omitted important characteristics of the studied patients, such as: duration of illness, type and response to therapy, gender, etc. Proteins that overlap across different tissue types and different studies have been highlighted: DPYSL, SYT1, STMN1, APOE, NME1, and others. The most common biological processes for them were the positive regulation of neurofibrillary tangle assembly, the regulation of amyloid fibril formation, lipoprotein catabolic process, the positive regulation of vesicle fusion, the positive regulation of oxidative stress-induced intrinsic apoptotic signaling pathway, removal of superoxide radicals, axon extension, and the regulation of actin filament depolymerization. MS-based proteomic profiling for a relevant study must accept a number of limitations, the most important of which is the need to compare different types of neurological and, in particular, epileptic disorders. Such a criterion could increase the specificity of the search work and, in the future, lead to the discovery of biomarkers for a particular disease.
Topics: Adult; Humans; Epilepsy, Temporal Lobe; Epilepsy; Proteins; Mass Spectrometry; Biomarkers; Temporal Lobe
PubMed: 37446307
DOI: 10.3390/ijms241311130 -
PloS One 2024This study aimed to evaluate the intervention effect of curcumin on hepatic fibrosis in rodent models through systematic review and meta-analysis, in order to provide... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This study aimed to evaluate the intervention effect of curcumin on hepatic fibrosis in rodent models through systematic review and meta-analysis, in order to provide meaningful guidance for clinical practice.
METHODS
A systematic retrieval of relevant studies on curcumin intervention in rats or mice hepatic fibrosis models was conducted, and the data were extracted. The outcome indicators included liver cell structure and function related indicators, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), albumin (ALB), ratio of albumin to globulin (A/G), total bilirubin (TBIL), bax protein, bcl-2 protein and index of liver, as well as the relevant indicators for evaluating the degree of hepatic fibrosis, such as hyaluronic acid (HA), laminin (LN), type I collagen (Collagen I), type III collagen (Collagen III), type III procollagen (PCIII), type III procollagen amino terminal peptide (PIIINP), type IV collagen (IV-C), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), α-Smooth muscle actin (α-SMA), hydroxyproline (HYP), platelet derived factor-BB (PDGF-BB), connective tissue growth factor (CTGF) and transforming growth factor-β1 (TGF-β1), and oxidative stress-related indicators, such as superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px). These results were then analyzed by meta-analysis. Studies were evaluated for methodological quality using the syrcle's bias risk tool.
RESULTS
A total of 59 studies were included in the meta-analysis, and the results showed that curcumin can reduce the levels of ALT, AST, ALP, TBIL, bax protein, and index of liver in hepatic fibrosis models. It can also reduce HA, LN, Collagen I, Collagen III, PCIII, PIIINP, IV-C, TNF-α, α-SMA, HYP, PDGF-BB, CTGF, TGF-β1 and MDA, and increase the levels of ALB, A/G, SOD, and GSH-Px in the hepatic fibrosis models. However, the effects of curcumin on bcl-2 protein, IL-6 in hepatic fibrosis models and index of liver in mice were not statistically significant.
CONCLUSION
The analysis results indicate that curcumin can reduce liver cell apoptosis by maintaining the stability of liver cell membrane, inhibit the activation and proliferation of hepatic stellate cells by reducing inflammatory response, and alleviate tissue peroxidation damage by clearing oxygen free radicals.
Topics: Animals; Liver Cirrhosis; Curcumin; Mice; Rats; Disease Models, Animal; Oxidative Stress; Liver
PubMed: 38781262
DOI: 10.1371/journal.pone.0304176 -
PeerJ 2024To elucidate the relationship between cancer-associated fibroblast (CAFs) biomarkers and the prognosis of breast cancer patients for individualized CAFs-targeting... (Meta-Analysis)
Meta-Analysis
BACKGROUND
To elucidate the relationship between cancer-associated fibroblast (CAFs) biomarkers and the prognosis of breast cancer patients for individualized CAFs-targeting treatment.
METHODOLOGY
PubMed, Web of Science, Cochrane, and Embase databases were searched for CAFs-related studies of breast cancer patients from their inception to September, 2023. Meta-analysis was performed using R 4.2.2 software. Sensitivity analyses were performed to explore the sources of heterogeneity. Funnel plot and Egger's test were used to assess the publication bias.
RESULTS
Twenty-seven studies including 6,830 patients were selected. Univariate analysis showed that high expression of platelet-derived growth factor receptor- (PDGFR-) ( = 0.0055), tissue inhibitor of metalloproteinase-2 (TIMP-2) ( < 0.0001), matrix metalloproteinase (MMP) 9 ( < 0.0001), MMP 11 ( < 0.0001) and MMP 13 ( = 0.0009) in CAFs were correlated with reduced recurrence-free survival (RFS)/disease-free survival (DFS)/metastasis-free survival (MFS)/event-free survival (EFS) respectively. Multivariate analysis showed that high expression of -smooth muscle actin (-SMA) ( = 0.0002), podoplanin (PDPN) ( = 0.0008), and PDGFR- ( = 0.0470) in CAFs was associated with reduced RFS/DFS/MFS/EFS respectively. Furthermore, PDPN and PDGFR- expression in CAFs of poorly differentiated breast cancer patients were higher than that of patients with relatively better differentiated breast cancer. In addition, there is a positive correlation between the expression of PDPN and human epidermal growth factor receptor-2 (HER-2).
CONCLUSIONS
The high expression of -SMA, PDPN, PDGFR- in CAFs leads to worse clinical outcomes in breast cancer, indicating their roles as prognostic biomarkers and potential therapeutic targets.
Topics: Humans; Female; Breast Neoplasms; Cancer-Associated Fibroblasts; Tissue Inhibitor of Metalloproteinase-2; Biomarkers, Tumor; Breast; Receptor, Platelet-Derived Growth Factor beta
PubMed: 38410801
DOI: 10.7717/peerj.16958 -
Journal of the American Heart... Dec 2020Background Human mesenchymal cells are culprit factors in vascular (patho)physiology and are hallmarked by phenotypic and functional heterogeneity. At present, they are... (Meta-Analysis)
Meta-Analysis
Background Human mesenchymal cells are culprit factors in vascular (patho)physiology and are hallmarked by phenotypic and functional heterogeneity. At present, they are subdivided by classic umbrella terms, such as "fibroblasts," "myofibroblasts," "smooth muscle cells," "fibrocytes," "mesangial cells," and "pericytes." However, a discriminative marker-based subclassification has to date not been established. Methods and Results As a first effort toward a classification scheme, a systematic literature search was performed to identify the most commonly used phenotypical and functional protein markers for characterizing and classifying vascular mesenchymal cell subpopulation(s). We next applied immunohistochemistry and immunofluorescence to inventory the expression pattern of identified markers on human aorta specimens representing early, intermediate, and end stages of human atherosclerotic disease. Included markers comprise markers for mesenchymal lineage (vimentin, FSP-1 [fibroblast-specific protein-1]/S100A4, cluster of differentiation (CD) 90/thymocyte differentiation antigen 1, and FAP [fibroblast activation protein]), contractile/non-contractile phenotype (α-smooth muscle actin, smooth muscle myosin heavy chain, and nonmuscle myosin heavy chain), and auxiliary contractile markers (h1-Calponin, h-Caldesmon, Desmin, SM22α [smooth muscle protein 22α], non-muscle myosin heavy chain, smooth muscle myosin heavy chain, Smoothelin-B, α-Tropomyosin, and Telokin) or adhesion proteins (Paxillin and Vinculin). Vimentin classified as the most inclusive lineage marker. Subset markers did not separate along classic lines of smooth muscle cell, myofibroblast, or fibroblast, but showed clear temporal and spatial diversity. Strong indications were found for presence of stem cells/Endothelial-to-Mesenchymal cell Transition and fibrocytes in specific aspects of the human atherosclerotic process. Conclusions This systematic evaluation shows a highly diverse and dynamic landscape for the human vascular mesenchymal cell population that is not captured by the classic nomenclature. Our observations stress the need for a consensus multiparameter subclass designation along the lines of the cluster of differentiation classification for leucocytes.
Topics: Atherosclerosis; Humans; Mesenchymal Stem Cells; Muscle, Smooth, Vascular
PubMed: 33190596
DOI: 10.1161/JAHA.120.017094 -
International Journal of Environmental... Dec 2019Physical, chemical, and social environments adversely affect the molecular process and results in cell signal transduction and the subsequent transcription factor...
DNA Methylation of Candidate Genes (ACE II, IFN-γ, AGTR 1, CKG, ADD1, SCNN1B and TLR2) in Essential Hypertension: A Systematic Review and Quantitative Evidence Synthesis.
Physical, chemical, and social environments adversely affect the molecular process and results in cell signal transduction and the subsequent transcription factor dysregulation, leading to impaired gene expression and abnormal protein synthesis. Stressful environments such as social adversity, isolation, sustained social threats, physical inactivity, and highly methylated diets predispose individuals to molecular level alterations such as aberrant epigenomic modulations that affect homeostasis and hemodynamics. With cardiovascular disease as the leading cause of mortality in the US and blacks/African Americans being disproportionately affected by hypertension (HTN) which contributes substantially to these deaths, reflecting the excess mortality and survival disadvantage of this sub-population relative to whites, understanding the molecular events, including epigenomic and socio-epigenomic modulations, is relevant to narrowing the black-white mortality risk differences. We aimed to synthesize epigenomic findings in HTN namely (a) angiotensin-converting enzyme 2 (ACE II) gene, (b) Toll-like receptor 2 (TLR2) gene, (c) interferon γ (IFN-γ) gene, and (d) Capping Actin Protein, Gelosin-Like () , adducin 1(ADD1) gene, (e) Tissue inhibitor of metalloproteinase 3 (), (f) mesoderm specific transcript (MEST) loci, (g) sodium channel epithelial 1 alpha subunit 2 (SCNN1B), (h) glucokinase (CKG) gene (i) angiotensin II receptor, type1 (AGTR1), and DNA methylation (mDNA). A systematic review and quantitative evidence synthesis (QES) was conducted using Google Scholar and PubMed with relevant search terms. Data were extracted from studies on: (a) Epigenomic modulations in HTN based on ACE II (b) TLR2, (c) IFN-γ gene, (d) , ADD1, , MEST loci, and mDNA. The random-effect meta-analysis method was used for a pooled estimate of the common effect size, while z statistic and I^2 were used for the homogeneity of the common effect size and between studies on heterogeneity respectively. Of the 642 studies identified, five examined hypermethylation while seven studies assessed hypomethylation in association with HTN. The hypermethylation of ACE II, SCNN1B, CKG, IFN-γ gene, and miR-510 promoter were associated with hypertension, the common effect size (CES) = 6.0%, 95% CI, -0.002-11.26. In addition, the hypomethylation of TLR2, IFN-γ gene, ADD1, AGTR1, and GCK correlated with hypertension, the CES = 2.3%, 95% CI, -2.51-7.07. The aberrant epigenomic modulation of ACE II, TLR2, IFN-γ, AGTR1, and GCK correlated with essential HTN. Transforming the environments resulting from these epigenomic lesions will facilitate early intervention mapping in reducing HTN in the US population, especially among socially disadvantaged individuals, particularly racial/ethnic minorities.
Topics: DNA Methylation; Essential Hypertension; Female; Genotype; Humans
PubMed: 31805646
DOI: 10.3390/ijerph16234829 -
Stem Cell Research & Therapy Jan 2021Mesenchymal stem cell (MSC) therapy shows great promise for diabetic kidney disease (DKD) patients. Research has been carried out on this topic in recent years. The main... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Mesenchymal stem cell (MSC) therapy shows great promise for diabetic kidney disease (DKD) patients. Research has been carried out on this topic in recent years. The main goals of this paper are to evaluate the therapeutic effects of MSCs on DKD through a meta-analysis and address the mechanism through a systematic review of the literature.
METHOD
An electronic search of the Embase, Cochrane Library, ISI Web of Science, PubMed, and US National Library of Medicine (NLM) databases was performed for all articles about MSC therapy for DKD, without species limitations, up to January 2020. Data were pooled for analysis with Stata SE 12.
RESULT
The MSC-treated group showed a large and statistically significant hypoglycemic effect at 1 week, 2 weeks, 3 weeks, 1 month, 2 months, 3 months, and 6 months. Total hypoglycemic effect was observed (SMD = - 1.954, 95%CI - 2.389 to - 1.519, p < 0.001; I = 85.1%). The overall effects on serum creatinine (SCr) and blood urea nitrogen (BUN) were analyzed, suggesting that MSC decreased SCr and BUN and mitigated the impairment of renal function (SCr: SMD = - 4.838, 95%CI - 6.789 to - 2.887, p < 0.001; I = 90.8%; BUN: SMD = - 4.912, 95%CI - 6.402 to - 3.422, p < 0.001; I = 89.3%). Furthermore, MSC therapy decreased the excretion of urinary albumin. Fibrosis indicators were assessed, and the results showed that transforming growth factor-β, collagen I, fibronectin, and α-smooth muscle actin were significantly decreased in the MSC-treated group compared to the control group.
CONCLUSION
MSCs might improve glycemic control and reduce SCr, BUN, and urinary protein. MSCs can also alleviate renal fibrosis. MSC therapy might be a potential treatment for DKD.
Topics: Blood Urea Nitrogen; Creatinine; Diabetes Mellitus; Diabetic Nephropathies; Fibrosis; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells
PubMed: 33413678
DOI: 10.1186/s13287-020-02108-5 -
Frontiers in Pharmacology 2022(common name: Earthworm, Chinese name: dilong) has been used in traditional Chinese medicine for thousands of years. Recently, a few scientific studies have...
(common name: Earthworm, Chinese name: dilong) has been used in traditional Chinese medicine for thousands of years. Recently, a few scientific studies have investigated the antifibrotic effects of Dilong extract (DE) and produced controversial results. We conducted a meta-analysis to make an informed decision on the antifibrotic effects of Dilong extract. The studies on antifibrotic effects of Dilong extract published until July 2022 in the scientific databases [PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), VIP database for Chinese Technical Periodicals, SinoMed and WanFang database] were reviewed. The RevMan 5.4.1 software was used for standardized mean difference (SMD) analysis. Two researchers independently reviewed all the studies, and their quality was assessed using the Cochrane risk of bias tool. A total of 325 studies were found in the scientific databases; however, only 13 studies met the criteria for analysis. Dilong extract treatment was associated with antifibrotic effects inhibiting the transforming growth factor beta 1 (TGF-β1, SMD = -3.16, 95% CI: -4.18, -2.14, < .00001) and alpha-smooth muscle actin (α-SMA: SMD = -2.57, 95% CI: -3.47, -1.66, < .00001). Dilong extract effectively reduces tissue fibrosis; thus, further scientific studies should be conducted to investigate and develop it for clinical use. https://www.crd.york.ac.uk/prospero/, identifier CRD42022357141.
PubMed: 36618931
DOI: 10.3389/fphar.2022.1039553 -
International Journal of Molecular... Nov 2021Cytotoxic necrotizing factor 1 (CNF1) is a bacterial virulence factor, the target of which is represented by Rho GTPases, small proteins involved in a huge number of... (Review)
Review
Cytotoxic necrotizing factor 1 (CNF1) is a bacterial virulence factor, the target of which is represented by Rho GTPases, small proteins involved in a huge number of crucial cellular processes. CNF1, due to its ability to modulate the activity of Rho GTPases, represents a widely used tool to unravel the role played by these regulatory proteins in different biological processes. In this review, we summarized the data available in the scientific literature concerning the observed in vitro effects induced by CNF1. An article search was performed on electronic bibliographic resources. Screenings were performed of titles, abstracts, and full-texts according to PRISMA guidelines, whereas eligibility criteria were defined for in vitro studies. We identified a total of 299 records by electronic article search and included 76 original peer-reviewed scientific articles reporting morphological or biochemical modifications induced in vitro by soluble CNF1, either recombinant or from pathogenic extracts highly purified with chromatographic methods. Most of the described CNF1-induced effects on cultured cells are ascribable to the modulating activity of the toxin on Rho GTPases and the consequent effects on actin cytoskeleton organization. All in all, the present review could be a prospectus about the CNF1-induced effects on cultured cells reported so far.
Topics: Actin Cytoskeleton; Bacterial Toxins; Cell Line; Enterotoxins; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Humans; rho GTP-Binding Proteins
PubMed: 34830494
DOI: 10.3390/ijms222212610 -
Frontiers in Pharmacology 2021Rhubarb, also known as Da Huang, is a traditional Chinese medicine, and it was often used as a laxative in the past. Recently, multiple studies have applied rhubarb to...
Rhubarb, also known as Da Huang, is a traditional Chinese medicine, and it was often used as a laxative in the past. Recently, multiple studies have applied rhubarb to treat diabetic nephropathy (DN). Anthraquinones, including emodin and rhein, have been extracted from rhubarb and used to explore the effective components and possible mechanisms of rhubarb for DN. Evaluating the efficacy of rhubarb may provide a scientific reference for the clinical application of rhubarb for the treatment of DN. 1) To evaluate the efficacy of rhubarb in the treatment of DN; 2) To identify the most effective ingredient of rhubarb for DN; 3) To explore the specific mechanism of rhubarb in treating DN. Data sources: related studies were identified by searching Cochrane Library, Ovid-EMBASE, PubMed, SinoMed, WanFang, VIP, CNKI, and other Chinese magazines. Assessment and analysis: SYRCLE's risk of bias tool for animal studies was used to assess the quality of articles. The meta-analysis was performed in accordance with the Cochrane Handbook for Systematic Reviews of Interventions. Data analysis adopted RevMan 5.3 and STATA 12.0 software. This study was published in the register with PROSPERO, number CRD42020204701. Aggregated data were collected from 27 eligible studies. The results illustrated an intense improvement in the following outcomes in rhubarb-treated animals with DN ( < 0.05): blood glucose, serum creatinine (Scr), blood urea nitrogen (BUN), albumin creatinine ratio (ACR), urine protein (UP), urinary albumin excretion (UAE), renal index (two kidneys weight/body weight, KW/BW), tubulointerstitial injury index (TII), transforming growth factor-beta1 (TGF-β1) mRNA and protein, alpha-smooth muscle actin (α-SMA) protein, and E-cadherin (E-cad) protein. Of these, DN animals with rhubarb exhibited a significantly higher level of E-cad protein. In addition, the level of the other outcomes mentioned above decreased significantly, while there was no significant association between the intervention and nephrin protein ( > 0.05). This systematic review and meta-analysis demonstrated that rhubarb has a positive therapeutic effect on animals with DN, which may provide confidence and some theoretical reference for clinical application to a certain extent.
PubMed: 34177560
DOI: 10.3389/fphar.2021.602816 -
Sexual Medicine Apr 2023Erectile dysfunction (ED) is a common disease among elderly men, and novel therapy methods are needed for drug-refractory ED. As an extracellular vesicle, stem...
INTRODUCTION
Erectile dysfunction (ED) is a common disease among elderly men, and novel therapy methods are needed for drug-refractory ED. As an extracellular vesicle, stem cell-derived exosomes displayed erectile function improvement in rat ED models in some preclinical studies. However, the therapeutic efficacy has not been comprehensively evaluated.
AIM
To study the therapeutic effects of stem cell-derived exosomes on ED in preclinical studies and to investigate the potential mechanisms responsible for the efficacy.
METHODS
The systematic literature search was conducted in Web of Science, PubMed, and Embase to retrieve studies utilizing stem cell-derived exosomes for ED treatment. We extracted data of intracavernous pressure/mean artery pressure (ICP/MAP), and cavernosum structural changes in rat ED models before and after stem cell-derived exosome therapy. RevMan 5.3 was used to perform meta-analyses of ICP/MAP and cavernosum microstructural changes. Publication bias was assessed with the Egger test and funnel plot by Stata 15.0 (StataCorp).
MAIN OUTCOME MEASURES
Outcomes included ICP/MAP, smooth muscle, and endothelial markers-such as the ratio of smooth muscle to collagen and the expression of α-SMA (alpha smooth muscle actin), CD31 (cluster of differentiation 31), nNOS and eNOS (neuronal and endothelial nitric oxide synthase), TGF-β1 (transforming growth factor β1), and caspase 3 protein-to evaluate erectile function and microstructural changes. Forest plots of effect sizes were performed.
RESULTS
Of 146 studies retrieved, 11 studies were eligible. Pooled analysis showed that stem cell-derived exosomes ameliorated damaged ICP/MAP (standardized mean difference, 3.68; 95% CI, 2.64-4.72; < .001) and structural changes, including the ratio of smooth muscle to collagen and the expression of α-SMA, CD31, nNOS, eNOS, TGF-β1, and caspase 3 protein. Subgroup analysis indicated that exosome type and ED model type made no difference to curative effects.
CONCLUSION
This meta-analysis suggests the therapeutic efficacy of stem cell-derived exosomes for ED. Exosomes may restore erectile function by optimizing cavernosum microstructures.
PubMed: 36910707
DOI: 10.1093/sexmed/qfac019