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Cancer Control : Journal of the Moffitt... 2022The previous reports on clusterin (CLU) levels in various types of cancer have been controversial and heterogeneous. The present meta-analysis has aimed to evaluate the... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The previous reports on clusterin (CLU) levels in various types of cancer have been controversial and heterogeneous. The present meta-analysis has aimed to evaluate the association between soluble CLU levels and the risk of different human cancers based on observational studies.
METHODS
A systematic literature review was conducted to determine the relevant eligible studies in English language from health-related electronic databases up to January 2021. Random effects models were used to calculate the summary standard mean difference (SMD) with 95% confidence intervals (CIs) to identify the correlation between CLU levels and cancer risk. The meta-regression, sensitivity, Galbraith, and subgroup analyses were performed to explore the source of between-study heterogeneity. Furthermore, the funnel plot and Egger's linear regression tests were carried out to evaluate the risk of publication bias.
RESULTS
According to 16 eligible articles, 3331 patients and 839 healthy controls were included in our meta-analysis. Overall, the CLU levels were significantly higher in various cancer cases compared to the healthy groups (SMD = 1.50, 95% CI = 0.47-2.53). Moreover, subgroup analysis based on types of cancer showed a significant correlation between CLU levels and the risk of digestive system cancers (SMD = 1.54, 95% CI = 0.91-2.18, <0.001), especially in HCC (SMD = 1.89, 95% CI = 0.76-3.03, = 0.001), and CRC (SMD = 1.63, 95% CI = 0.0-3.23, = 0.048).
CONCLUSION
The present meta-analysis indicates a significant association of CLU levels with the risk of digestive system cancers such as hepatocellular carcinoma and colorectal cancer. Therefore, CLU can be monitored as a novel molecular biomarker for the prognosis and diagnosis of various types of cancers particularly in the digestive system.
Topics: Carcinoma, Hepatocellular; Clusterin; Humans; Liver Neoplasms; Prognosis; Risk
PubMed: 35465749
DOI: 10.1177/10732748211038437 -
PloS One 2017A number of genetic loci were found to be associated with dystonia. Quite a few studies have been contacted to examine possible contribution of TOR1A variants to the... (Meta-Analysis)
Meta-Analysis Review
IMPORTANCE
A number of genetic loci were found to be associated with dystonia. Quite a few studies have been contacted to examine possible contribution of TOR1A variants to the risk of dystonia, but their results remain conflicting. The aim of the present study was to systematically evaluate the effect of TOR1A gene SNPs on dystonia and its phenotypic subtypes regarding the body distribution.
METHODS
We performed a systematic review of Pubmed database to identify all available studies that reported genotype frequencies of TOR1A SNPs in dystonia. In total 16 studies were included in the quantitative analysis. Odds ratios (ORs) were calculated in each study to estimate the influence of TOR1A SNPs genotypes on the risk of dystonia. The fixed-effects model and the random effects model, in case of high heterogeneity, for recessive and dominant mode of inheritance as well as the free generalized odds ratio (ORG) model were used to calculate both the pooled point estimate in each study and the overall estimates.
RESULTS
Rs1182 was found to be associated with focal dystonia in recessive mode of inheritance [Odds Ratio, OR (95% confidence interval, C.I.): 1.83 (1.14-2.93), Pz = 0.01]. In addition, rs1801968 was associated with writer's cramp in both recessive and dominant modes [OR (95%C.I.): 5.99 (2.08-17.21), Pz = 0.00009] and [2.48 (1.36-4.51), Pz = 0.003) respectively and in model free-approach [ORG (95%C.I.): 2.58 (1.45-4.58)].
CONCLUSIONS
Our meta-analysis revealed a significant implication of rs1182 and rs1801968 TOR1A variants in the development of focal dystonia and writer's cramp respectively. TOR1A gene variants seem to be implicated in dystonia phenotype.
Topics: Databases, Factual; Dystonia; Dystonic Disorders; Genetic Predisposition to Disease; Humans; Molecular Chaperones; Odds Ratio; Polymorphism, Single Nucleotide
PubMed: 28081261
DOI: 10.1371/journal.pone.0169934 -
Molecules (Basel, Switzerland) Dec 2017Conformational diseases represent a new aspect of proteomic medicine where diagnostic and therapeutic paradigms are evolving. In this context, the early biomarkers for... (Meta-Analysis)
Meta-Analysis Review
Conformational diseases represent a new aspect of proteomic medicine where diagnostic and therapeutic paradigms are evolving. In this context, the early biomarkers for target cell failure (neurons, β-cells, etc.) represent a challenge to translational medicine and play a multidimensional role as biomarkers and potential therapeutic targets. This systematic review, which follows the PICO and Prisma methods, analyses this new-fangled multidimensionality, its strengths and limitations, and presents the future possibilities it opens up. The nuclear diagnosis methods are immunoassays: ELISA, immunodot, western blot, etc., while the therapeutic approach is focused on pharmaco- and molecular chaperones.
Topics: Amyloid; Animals; Biomarkers; Disease; Enzyme-Linked Immunosorbent Assay; Humans; Protein Aggregates; Protein Conformation
PubMed: 29286329
DOI: 10.3390/molecules23010079 -
Frontiers in Endocrinology 2021Pancreatic neuroendocrine tumors (PanNETs) are a heterogeneous group of neoplasms with increasing incidence and unpredictable behavior. Whole-exome sequencing recently... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pancreatic neuroendocrine tumors (PanNETs) are a heterogeneous group of neoplasms with increasing incidence and unpredictable behavior. Whole-exome sequencing recently has shown very frequent somatic mutations in the alpha-thalassemia/mental retardation X-linked (ATRX) and death domain-associated protein (DAXX) genes in PanNETs. And the prognostic significance of altered ATRX/DAXX genes in PanNETs patients have been revealed in several reports. However, many of these include small sample size and hold controversial opinions. To increase statistical power, we performed a systematic review and meta-analysis to determine a pooled conclusion. We examined the impact of altered ATRX/DAXX genes mainly on overall survival (OS), disease-free survival (DFS) and relapse-free survival (RFS) in PanNETs.
METHODS
Eligible studies were identified and quality was assessed using multiple search strategies (last search May 2021). Data were collected from studies about prognostic significance of altered ATRX/DAXX in PanNETs. Studies were pooled, and combined hazard ratios (HRs) with 95% confidence intervals (CIs) were used to estimate strength of the associations.
RESULTS
Fourteen studies involving 2313 patients treated for PanNETs were included. After evaluating for publication bias, disease-free survival and relapse-free survival was significantly shortened in patients with altered ATRX/DAXX gene, with combined HR 5.05 (95% confidence interval (CI): 1.58-16.20, = 0.01) and 3.21 (95% confidence interval (CI): 1.44-7.16, < 0.01) respectively. However, the combined data showed there were no difference between patients with altered ATRX/DAXX gene or not in overall survival, with a combined HR 0.71 (95% confidence interval (CI): 0.44-1.15, = 0.23). We also performed a subgroup analysis with metastatic patients in overall survival, showing a combined HR 0.22 (95% confidence interval (CI): 0.11-0.48, = 0.96). The small number of studies and paucity of multivariate analyses are the limitations of our study.
CONCLUSIONS
This is the first rigorous pooled analysis assessing ATRX/DAXX mutation as prognostic biomarkers in PanNETs. Patients with altered ATRX/DAXX gene would have poor DFS according to the combined data. And altered ATRX/DAXX genes in metastatic patients showed a trend towards improved overall survival, although the difference did not reach statistical significance.
Topics: Co-Repressor Proteins; Humans; Molecular Chaperones; Neuroendocrine Tumors; Pancreatic Neoplasms; Prognosis; X-linked Nuclear Protein
PubMed: 34220718
DOI: 10.3389/fendo.2021.691557 -
Biomolecules Oct 2022Alzheimer's disease (AD) is considered a chronic and debilitating neurological illness that is increasingly impacting older-age populations. Some proteins, including... (Review)
Review
Alzheimer's disease (AD) is considered a chronic and debilitating neurological illness that is increasingly impacting older-age populations. Some proteins, including clusterin ( or ) transporter, can be linked to AD, causing oxidative stress. Therefore, its activity can affect various functions involving complement system inactivation, lipid transport, chaperone activity, neuronal transmission, and cellular survival pathways. This transporter is known to bind to the amyloid beta (Aβ) peptide, which is the major pathogenic factor of AD. On the other hand, this transporter is also active at the blood-brain barrier (BBB), a barrier that prevents harmful substances from entering and exiting the brain. Therefore, in this review, we discuss and emphasize the role of the transporter and -linked molecular mechanisms at the BBB interface in the pathogenesis of AD.
Topics: Humans; Clusterin; Alzheimer Disease; Amyloid beta-Peptides; Blood-Brain Barrier; Membrane Transport Proteins; Lipids
PubMed: 36291661
DOI: 10.3390/biom12101452 -
International Journal of Molecular... Mar 2023Schizophrenia is a severe psychiatric illness affecting almost 25 million people worldwide and is conceptualized as a disorder of synaptic plasticity and brain... (Review)
Review
Canonical and Non-Canonical Antipsychotics' Dopamine-Related Mechanisms of Present and Next Generation Molecules: A Systematic Review on Translational Highlights for Treatment Response and Treatment-Resistant Schizophrenia.
Schizophrenia is a severe psychiatric illness affecting almost 25 million people worldwide and is conceptualized as a disorder of synaptic plasticity and brain connectivity. Antipsychotics are the primary pharmacological treatment after more than sixty years after their introduction in therapy. Two findings hold true for all presently available antipsychotics. First, all antipsychotics occupy the dopamine D2 receptor (D2R) as an antagonist or partial agonist, even if with different affinity; second, D2R occupancy is the necessary and probably the sufficient mechanism for antipsychotic effect despite the complexity of antipsychotics' receptor profile. D2R occupancy is followed by coincident or divergent intracellular mechanisms, implying the contribution of cAMP regulation, β-arrestin recruitment, and phospholipase A activation, to quote some of the mechanisms considered canonical. However, in recent years, novel mechanisms related to dopamine function beyond or together with D2R occupancy have emerged. Among these potentially non-canonical mechanisms, the role of Na channels at the dopamine at the presynaptic site, dopamine transporter (DAT) involvement as the main regulator of dopamine concentration at synaptic clefts, and the putative role of antipsychotics as chaperones for intracellular D2R sequestration, should be included. These mechanisms expand the fundamental role of dopamine in schizophrenia therapy and may have relevance to considering putatively new strategies for treatment-resistant schizophrenia (TRS), an extremely severe condition epidemiologically relevant and affecting almost 30% of schizophrenia patients. Here, we performed a critical evaluation of the role of antipsychotics in synaptic plasticity, focusing on their canonical and non-canonical mechanisms of action relevant to the treatment of schizophrenia and their subsequent implication for the pathophysiology and potential therapy of TRS.
Topics: Humans; Antipsychotic Agents; Dopamine; Schizophrenia; Schizophrenia, Treatment-Resistant; beta-Arrestins
PubMed: 36983018
DOI: 10.3390/ijms24065945 -
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 -
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 -
Orphanet Journal of Rare Diseases Apr 2017Hereditary proximal spinal muscular atrophy (SMA) is a severe neuromuscular disease of childhood caused by homozygous loss of function of the survival motor neuron (SMN)... (Review)
Review
BACKGROUND
Hereditary proximal spinal muscular atrophy (SMA) is a severe neuromuscular disease of childhood caused by homozygous loss of function of the survival motor neuron (SMN) 1 gene. The presence of a second, nearly identical SMN gene (SMN2) in the human genome ensures production of residual levels of the ubiquitously expressed SMN protein. Alpha-motor neurons in the ventral horns of the spinal cord are most vulnerable to reduced SMN concentrations but the development or function of other tissues may also be affected, and cardiovascular abnormalities have frequently been reported both in patients and SMA mouse models.
METHODS
We systematically reviewed reported cardiac pathology in relation to SMN deficiency. To investigate the relevance of the possible association in more detail, we used clinical classification systems to characterize structural cardiac defects and arrhythmias.
CONCLUSIONS
Seventy-two studies with a total of 264 SMA patients with reported cardiac pathology were identified, along with 14 publications on SMA mouse models with abnormalities of the heart. Structural cardiac pathology, mainly septal defects and abnormalities of the cardiac outflow tract, was reported predominantly in the most severely affected patients (i.e. SMA type 1). Cardiac rhythm disorders were most frequently reported in patients with milder SMA types (e.g. SMA type 3). All included studies lacked control groups and a standardized approach for cardiac evaluation. The convergence to specific abnormalities of cardiac structure and function may indicate vulnerability of specific cell types or developmental processes relevant for cardiogenesis. Future studies would benefit from a controlled and standardized approach for cardiac evaluation in patients with SMA.
Topics: Heart; Humans; Motor Neurons; Muscular Atrophy, Spinal; Spinal Muscular Atrophies of Childhood; Survival of Motor Neuron 1 Protein; Survival of Motor Neuron 2 Protein
PubMed: 28399889
DOI: 10.1186/s13023-017-0613-5 -
Molecular Medicine (Cambridge, Mass.) Aug 2023Glucose-Regulated Protein 78 (GRP78) is a chaperone protein that is predominantly expressed in the lumen of the endoplasmic reticulum. GRP78 plays a crucial role in... (Review)
Review
Glucose-Regulated Protein 78 (GRP78) is a chaperone protein that is predominantly expressed in the lumen of the endoplasmic reticulum. GRP78 plays a crucial role in protein folding by assisting in the assembly of misfolded proteins. Under cellular stress conditions, GRP78 can translocate to the cell surface (csGRP78) were it interacts with different ligands to initiate various intracellular pathways. The expression of csGRP78 has been associated with tumor initiation and progression of multiple cancer types. This review provides a comprehensive analysis of the existing evidence on the roles of GRP78 in various types of cancer and other human pathology. Additionally, the review discusses the current understanding of the mechanisms underlying GRP78's involvement in tumorigenesis and cancer advancement. Furthermore, we highlight recent innovative approaches employed in downregulating GRP78 expression in cancers as a potential therapeutic target.
Topics: Humans; Endoplasmic Reticulum Chaperone BiP; Neoplasms; Cell Transformation, Neoplastic; Endoplasmic Reticulum
PubMed: 37605113
DOI: 10.1186/s10020-023-00706-6