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Cell Stress & Chaperones Nov 2023Metabolic disorders, such as obesity, type 2 diabetes mellitus (T2DM), and metabolic syndrome (MS) are related to chronic pro-inflammatory conditions. Evidence suggests... (Meta-Analysis)
Meta-Analysis
Metabolic disorders, such as obesity, type 2 diabetes mellitus (T2DM), and metabolic syndrome (MS) are related to chronic pro-inflammatory conditions. Evidence suggests that heat shock proteins are linked to metabolic disorders. Intracellular HSP70 (iHSP70) is mandatory for normal insulin signalling, and proteostasis, and exerts a powerful anti-inflammatory role. On the other hand, the extracellular (eHSP72) is linked with a pro-inflammatory state and induces insulin resistance in humans. Then, we conducted a systematic review with meta-analysis to summarize the data of HSP70 in people with and without metabolic disorders. PubMed, Embase, Scopus, and Web of Science databases were used. Eligibility criteria included observational and baseline data of experimental studies that assessed iHSP70 and/or eHSP72 in adults with metabolic disorders and healthy people. The risk of bias was assessed by the Newcastle-Ottawa scale. Meta-analysis was performed using a random-effect model and the mean difference was estimated for eHSP72 and the standardized mean difference for iHSP70. A total of 11,255 articles were retrieved, 31 articles were assessed for eligibility and 15 were included for data extraction. There was no difference in eHSP72 between metabolic disorders and healthy controls (mean difference (MD) = 0.11; 95% confidence interval (CIs) = -0.05 to 0.27; I = 95%). Subgroup analysis showed higher levels of eHSP72 in T2DM people than healthy ones (MD = 0.32; 95% CIs = 0.17 to 0.47; I = 92%). For iHSP70 no difference was found (standardized mean difference (SMD) =-0.24; 95% CIs =-1.62 to 1.15; I = 86%). Our results suggest that eHSP72 levels may be dependent on metabolic condition and no difference in iHSP70 levels are attributed to high heterogeneity level between studies (PROSPERO REGISTRATION: CRD42022323514).
Topics: Adult; Humans; Diabetes Mellitus, Type 2; HSP70 Heat-Shock Proteins; Insulin Resistance; Obesity; Insulin
PubMed: 37495770
DOI: 10.1007/s12192-023-01368-3 -
Metabolic Brain Disease Feb 2019Studies have showed that high clusterin (CLU) concentration was associated with increased risk of dementia. However, the results based on small samples remained... (Meta-Analysis)
Meta-Analysis
Studies have showed that high clusterin (CLU) concentration was associated with increased risk of dementia. However, the results based on small samples remained controversial. The aim of our study was to determine the relationship between CLU concentration and the late-life cognitive outcomes including mild cognitive impairment (MCI), Alzheimer's disease (AD), vascular dementia (VAD), Parkinson's disease related dementia (PDD), Lewy body dementia (DLB) and frontotemporal dementia (FTD). A comprehensive search was conducted to screen the eligible studies in online database PubMed, Web of Science and Embase from 1950 to January 2017 according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) checklist. The CLU concentration data in brain tissue, cerebrospinal fluid (CSF), serum and plasma was collected to determine the strength of this association. The results were presented with standard difference of the mean (SDM) with 95% confidence intervals (CIs). A total of 28 studies were identified to calculate the association between CLU concentration and dementia. The results showed that the CLU concentration in the plasma (SDM = 0.73, 95% CI 0.26-1.19, P = 0.002) and brain tissue (SDM = 0.71, 95% CI 0.10-1.32, P = 0.022) was increased in dementia compared to normal control. Subgroup analysis showed that the plasma CLU concentration was significantly increased only in the AD group (SDM = 1.85, 95% CI 0.84-2.85, P < 0.001), but not in MCI or other dementias. No association was found between serum and CSF clusterin concentration and dementia. This meta-analysis indicates that high CLU concentration in the plasma and brain is associated with dementia, especially in AD.
Topics: Alzheimer Disease; Brain; Clusterin; Cognitive Dysfunction; Dementia; Dementia, Vascular; Humans
PubMed: 30291488
DOI: 10.1007/s11011-018-0325-0 -
The Science of the Total Environment Sep 2022The effect of high-altitude (HA) on venous thromboembolism (VTE) and its mechanism remains ambiguous. To clarify this, we aimed to conduct a meta-analysis and systematic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The effect of high-altitude (HA) on venous thromboembolism (VTE) and its mechanism remains ambiguous. To clarify this, we aimed to conduct a meta-analysis and systematic review to evaluate the incidence of VTE at HA and comparatively low altitude (LA) and figure out the intrinsic risk factors such as susceptibility genes of patients with VTE at HA.
METHODS
We selected studies that explored the risk factors for HA and VTE by searching PubMed, Embase, and Web of Science to analyze the impact of HA on VTE. All relevant studies before August 2021 were screened using the terms ([high altitude] OR [plateau] OR [mountain]) AND ([venous thromboembolism] OR [deep vein thrombosis] OR [pulmonary embolism]). Latest studies on the gene of HA-VTE patients were also summarized and analyzed.
RESULTS
Fifteen studies were eventually assessed, and the overall numbers of subjects with and without VTE were 1475 and 286,926 respectively. The overall incidence of VTE, deep vein thrombosis (DVT) and pulmonary embolism (PE) in the HA group was significantly higher than that in the LA group (P < 0.01). The overall incidence of VTE, DVT and PE in the HA group was significantly higher than that in the LA group at 30 days post operation (P < 0.05, P < 0.05 and P < 0.01, respectively). At 90 days post operation, incidence of VTE and PE in the HA group was higher than that in the LA group (P < 0.01and P < 0.01, respectively), but there was no difference in the incidence of DVT (P = 0.07). Regarding endogenous factors, the analysis of genes in patients with HA-VTE revealed numerous targeted genes such as ANG, ACE, lncRNA-LINC00 659/UXT-AS1 and GP4.
CONCLUSIONS
We observed a significant association between HA and the overall incidence of VTE and that at 30/90 days post operation, indicating that HA may be a risk factor for VTE.
Topics: Humans; Altitude; Cell Cycle Proteins; Genetic Predisposition to Disease; Incidence; Molecular Chaperones; Pulmonary Embolism; Risk Factors; Venous Thromboembolism; Venous Thrombosis
PubMed: 35691358
DOI: 10.1016/j.scitotenv.2022.156632 -
Breast (Edinburgh, Scotland) Oct 2013Pharmacological inhibition of Hsp90 shows great promise in breast cancer treatment. This is the first systematic review to synthesize all available data and to evaluate... (Review)
Review
PURPOSE
Pharmacological inhibition of Hsp90 shows great promise in breast cancer treatment. This is the first systematic review to synthesize all available data and to evaluate the efficacy and safety of Hsp90 inhibitors in breast cancer.
METHODS
This study was performed in accordance with the PRISMA guidelines. Eligible articles were identified by a search of MEDLINE and ClinicalTrials.gov databases, using a predefined combination of the terms "breast", "cancer", "Hsp90", "inhibitors".
RESULTS
Overall, 19 articles (190 patients) were eligible. The greatest clinical activity has been observed on the field of HER2-positive metastatic breast cancer. However, accumulating data suggest that Hsp90 inhibitors may play a significant role in the treatment of triple negative and aromatase inhibitor-resistant breast cancer.
CONCLUSION
In the last decade, the development of Hsp90 inhibitors has moved forward rapidly; however, no phase III trials have been conducted and none agent has been approved for use in the clinical practice.
Topics: Adenine; Antineoplastic Agents; Benzamides; Benzoquinones; Biomarkers, Tumor; Female; Glycine; HSP70 Heat-Shock Proteins; HSP90 Heat-Shock Proteins; Humans; Indazoles; Isoxazoles; Lactams, Macrocyclic; Pyridines; Resorcinols; Triazoles; Triple Negative Breast Neoplasms
PubMed: 23870456
DOI: 10.1016/j.breast.2013.06.003 -
Arquivos Brasileiros de Cardiologia Jul 2015Acute myocardial infarction is the leading cause of morbidity and mortality worldwide. Furthermore, research has shown that exercise, in addition to reducing... (Review)
Review
BACKGROUND
Acute myocardial infarction is the leading cause of morbidity and mortality worldwide. Furthermore, research has shown that exercise, in addition to reducing cardiovascular risk factors, can also protect the heart against injury due to ischemia and reperfusion through a direct effect on the myocardium. However, the specific mechanism involved in exerciseinduced cardiac preconditioning is still under debate.
OBJECTIVE
To perform a systematic review of the studies that have addressed the mechanisms by which aerobic exercise promotes direct cardioprotection against ischemia and reperfusion injury.
METHODS
A search was conducted using MEDLINE, Literatura Latino-Americana e do Caribe de Informação em Ciências da Saúde, and Scientific Electronic Library Online databases. Data were extracted in a standardized manner by two independent researchers, who were responsible for assessing the methodological quality of the studies.
RESULTS
The search retrieved 78 studies; after evaluating the abstracts, 30 studies were excluded. The manuscripts of the remaining 48 studies were completely read and, of these, 20 were excluded. Finally, 28 studies were included in this systematic review.
CONCLUSION
On the basis of the selected studies, the following are potentially involved in the cardioprotective response to exercise: increased heat shock protein production, nitric oxide pathway involvement, increased cardiac antioxidant capacity, improvement in ATP-dependent potassium channel function, and opioid system activation. Despite all the previous investigations, further research is still necessary to obtain more consistent conclusions.
Topics: Antioxidants; Exercise; Exercise Therapy; Heat-Shock Proteins; Humans; KATP Channels; Myocardial Infarction; Myocardial Reperfusion Injury; Time Factors
PubMed: 25830711
DOI: 10.5935/abc.20150024 -
Metabolic Brain Disease Aug 2017Clusterin polymorphism (rs9331888) was reported to be associated with the susceptibility to alzheimer's disease (AD). Nevertheless, the results were inconclusive. To... (Meta-Analysis)
Meta-Analysis Review
Clusterin polymorphism (rs9331888) was reported to be associated with the susceptibility to alzheimer's disease (AD). Nevertheless, the results were inconclusive. To derive a more precise estimation of this association, this meta-analysis was conducted. We've conducted a comprehensive search of PubMed, Embase, CNKI and AlzGene database for case-control studies published throughout October, 2016 that evaluated the role of rs9331888 gene variants in AD patients. Odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated to assess the strength of associations between the rs9331888/C > G polymorphism and AD disease. A total of 9 studies were enrolled in the Meta Analysis. The overall analysis revealed a significant association between the rs9331888/C > G polymorphism and AD disease in the recessive model (GG vs. GC + CC: OR = 1.11, 95% CI: 1.05-1.18; P < 0.01). Sub-group analysis revealed that the Caucasian populations which with recessive model (GG vs. GC + CC: OR = 1.12, 95% CI: 1.06-1.2; P < 0.01) were dramatically related to AD, while no significant association was found in the Chinese populations among the five genetic models. Our meta-analysis demonstrated that the rs9331888/C > G polymorphism in the clusterin gene might contribute to AD susceptibility especially in Caucasian populations. Whereas the relationship of the polymorphism to the disease in Chinese populations was still in controversial. Additional well-designed studies, with larger sample sizes, are required to further elucidate this association.
Topics: Alleles; Alzheimer Disease; Asian People; China; Clusterin; Genetic Predisposition to Disease; Genotype; Humans; Polymorphism, Single Nucleotide; White People
PubMed: 28168383
DOI: 10.1007/s11011-017-9957-8 -
Anticancer Research Mar 2018Studies have focused on heat shock protein (Hsp) inhibitors as potential treatment agents in breast cancer, with controversial results. Adopting a pathophysiological... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND/AIM
Studies have focused on heat shock protein (Hsp) inhibitors as potential treatment agents in breast cancer, with controversial results. Adopting a pathophysiological perspective, this systematic review aims to synthesize the evidence examining the association between Hsp70/Hsp90 expression and breast cancer prognosis, as well as prognosis-related clinicopathological indices. Secondarily, changes in Hsp70/Hsp90 expression in the continuum of breast neoplasia were assessed.
MATERIALS AND METHODS
Hsp70/Hsp90 expression was approached globally, quantified by means of immunohistochemistry, western blot or PCR. This study was performed in accordance with the PRISMA guidelines. Relevant studies were sought in PubMed, up to December 31, 2015.
RESULTS
A total of 23 eligible studies were identified (7,288 breast cancer cases). High Hsp90 expre s sion was associated with worse overall survival (pooled RR=1.48, 95%CI=1.21-1.82) and marginally with worse disease-free survival. High Hsp70 expression also correlated with worse disease-free survival (pooled RR=1.77, 95%CI=1.71-2.82). Hsp70 intense expression correlated with ER positivity (pooled OR=3.51, 95%CI=1.31-9.40) and PR positivity (pooled OR=2.48, 95%CI=1.39-4.44). No significant associations were noted between Hsp70/Hsp90 expression and clinicopathological variables including histological grade, tumor size, nodal metastasis or patient age at diagnosis. No clear pattern emerged for Hsp70/Hsp90 expression along the breast neoplasia continuum.
CONCLUSION
This systematic review and meta-analysis highlights the prognostic role of Hsp90 and Hsp70 expression in breast cancer. Further high-quality studies, with detailed reporting are needed to provide epidemiological evidence complementing the findings of ongoing clinical trials on Hsp inhibitors.
Topics: Breast Neoplasms; Disease-Free Survival; Gene Expression Regulation, Neoplastic; HSP70 Heat-Shock Proteins; HSP90 Heat-Shock Proteins; Humans; Immunohistochemistry; Prognosis; Reverse Transcriptase Polymerase Chain Reaction
PubMed: 29491085
DOI: 10.21873/anticanres.12384 -
Current Problems in Cardiology Feb 2023Transient receptor potential (TRP) family play critical roles in cardiovascular system. TRPM family as largest TRP subfamily is non-voltage Ca2+-activated selective... (Review)
Review
Transient receptor potential (TRP) family play critical roles in cardiovascular system. TRPM family as largest TRP subfamily is non-voltage Ca2+-activated selective channels which has 8 members. This study aimed to discuss the role of TRPM family in cardiovascular system and diseases. Systematic search was performed covering PubMed, ISI Web of Science, and Google Scholar from inception until June 2021 using related keywords and Mesh terms for English studies with human, animal and in-vitro subjects. Finally 10 studies were selected for data extraction. Reviewing the articles showed that TRPM2, TRPM4, TRPM5, TRPM6 and TRPM7 play important roles in cardiovascular system and diseases. TRPM2 could be activated by reactive oxygen species (ROS) and effects on cardiac injury and cardiac fibrosis. TRPM7 and TRPM6 also have been reported to be associated with cardiac fibrosis and atrial fibrosis development respectively. TRPM4 channels contributed to resting membrane potential of cerebral artery smooth muscle cells and atrial contraction. TRPM5 channels are bitter taste sensors and prevent high salt intake and consequently high blood pressure due to the high salt intake. In conclusion based on the proof of the effectiveness of some members of TRPM family in the cardiovascular system, research on other members of this channel group seems to be useful and necessary to find their possible connection to the cardiovascular system.
Topics: Animals; Humans; TRPM Cation Channels; Sodium Chloride, Dietary; Membrane Potentials; Clusterin; Cardiovascular System; Protein Serine-Threonine Kinases
PubMed: 34644560
DOI: 10.1016/j.cpcardiol.2021.101012 -
Pathology, Research and Practice Feb 2023GRP78 is a chaperone with anti-apoptotic function associated with aggressive tumors. This systematic review aimed to evaluate GRP78 expression in cancer and its relation... (Meta-Analysis)
Meta-Analysis Review
GRP78 is a chaperone with anti-apoptotic function associated with aggressive tumors. This systematic review aimed to evaluate GRP78 expression in cancer and its relation to prognosis outcomes. This review was conducted in different databases searching for human cancer studies assessing GRP78 immunohistochemical levels on tissue samples. A total of 98 manuscripts were included. In 62% of the studies, GRP78 was associated with a worse prognosis. A meta-analysis included 29 studies that detected a significantly higher expression of GRP78 in cancer tissues (RR= 2.35, 95% CI 1.75-3.15) compared to control. A meta-analysis of 3 and 5-years Overall Survival revealed an increased risk of death for tumors with high expression of GRP78 (RR=1.36, 95%CI 1.16-1,59, I = 57%) and (RR=1.65, 95%CI 1.22-2.21, I =64%), respectively. GRP78 is an important prognostic biomarker for different types of cancer and a promising therapeutic target.
Topics: Humans; Endoplasmic Reticulum Chaperone BiP; Heat-Shock Proteins; Prognosis; Neoplasms; Biomarkers; Glucose
PubMed: 36610326
DOI: 10.1016/j.prp.2023.154301 -
Otology & Neurotology : Official... Feb 2013We reviewed case-control studies concerning the diagnostic accuracy of Heat Shock Protein 70 (Hsp-70) auto antibodies in the detection of immunomediated inner ear... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
We reviewed case-control studies concerning the diagnostic accuracy of Heat Shock Protein 70 (Hsp-70) auto antibodies in the detection of immunomediated inner ear disease.
MATERIALS AND METHODS
We searched for relevant articles published in English language on PubMed and Scopus up to December 2011. A quality assessment of the retrieved articles was performed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) 2 tool. Pooled data on the accuracy of the test were calculated, where possible.
RESULTS
Three articles were deemed eligible. Among them, 2 evaluated the relationship between Hsp-70 and immunomediated inner ear disease by using the Western blot, whereas one report used the enzyme-linked immunosorbent assay method. Pooled sensitivity of Western blot test for Hsp-70 was 0.70 (95% confidence interval [CI], 0.59-0.80), with a large heterogeneity (I = 72.7%), and pooled specificity was 0.98 (95% CI, 0.87-1.00), with an I of 61.0%. Pooled positive likelihood ratios (LR) was 14.7 (95% CI, 2.1-104.1; I = 31.4%), and pooled negative LR was 0.32 (95% CI, 0.10-0.70; I = 78.8%). Sensitivity and specificity of enzyme-linked immunosorbent assay test for Hsp-70 auto antibodies was 0.85 (95% CI, 0.55-0.98) and 0.98 (95% CI, 0.86-1.00). Risk of bias was performed by using QUADAS 2 tool, with high scores obtained for patient selection and index test domains and low for the applicability criterion.
DISCUSSION
This review shows that studies on autoimmune hearing loss diagnosis based on the detection of Hsp-70 autoantibodies used different inclusion and methodologic criteria and are affected from potential bias. Additional studies are actually required to identify an accurate laboratory diagnostic method for the autoimmune hearing loss.
Topics: Antibodies; Autoimmune Diseases; Blotting, Western; Data Interpretation, Statistical; Enzyme-Linked Immunosorbent Assay; HSP70 Heat-Shock Proteins; Hearing Loss; Humans; Likelihood Functions; Publication Bias; Research Design; Sensitivity and Specificity
PubMed: 23295728
DOI: 10.1097/MAO.0b013e31827d0b8b