-
Reproduction (Cambridge, England) Apr 2021Proteomic approaches have been widely used in reproductive studies to uncover protein biomarkers of bull fertility. Seminal plasma is one of the most relevant sources of...
Proteomic approaches have been widely used in reproductive studies to uncover protein biomarkers of bull fertility. Seminal plasma is one of the most relevant sources of these proteins that may influence sperm physiology. Nonetheless, there are still gaps in existing knowledge in the functional attributes of seminal proteins. Thus, we reviewed the relationships between seminal plasma proteins and bull fertility by conducting a systematic review with data obtained from 71 studies. This review showed that the associations related to fertility improvement with the use of total seminal plasma proteins are still controversial. None of the studies explored the sperm fertilizing ability following these interactions. By contrast, the exposure to a single protein, such as osteopontin, binder of sperm proteins, and heparin binding proteins, can increment sperm motility, capacitation, and fertilizing ability by modulating intracellular calcium concentrations, removing lipids from sperm membranes, and regulating the acrosome reaction. Variations in protein analyses and the protein contents and their abundances between animals contributed to the difficulty of establishing protein biomarkers of fertilizing potential of the bull sperm. Indeed, the heterogenicity of methodologies was a limitation of this review. Standardized methods of seminal protein analyses, as well as sperm endpoints, may minimize such discrepancies. In conclusion, potential biomarkers of sperm parameters are still to be established. Future studies should evaluate protein isoforms and how they interact with sperm to ascertain their biological functions.
Topics: Animals; Cattle; Fertility; Male; Reproduction; Seminal Plasma Proteins
PubMed: 33606662
DOI: 10.1530/REP-20-0392 -
European Journal of Cancer (Oxford,... May 2005Glutathione s-transferase (GST) polymorphisms (GSTM1, GSTP1 and GSTT1) have been considered as risk factors for developing acute leukaemia in a number of studies;... (Meta-Analysis)
Meta-Analysis Review
Glutathione s-transferase (GST) polymorphisms (GSTM1, GSTP1 and GSTT1) have been considered as risk factors for developing acute leukaemia in a number of studies; however the overall results of such studies are inconsistent. To investigate a putative association of GST polymorphisms with the risk of acute leukaemia, we performed a systematic review and meta-analysis of 30 published case-control studies. To take into account the possibility of heterogeneity across the studies, a statistical test was performed. The pooled odds ratios (ORs) were assessed using both a fixed-effects and a random-effects model. The pooled OR of acute leukaemia risks associated with GSTM1 null genotype, GSTP1 Val105 allele and GSTT1 null genotype were 1.22 (95% confidence interval (CI) 1.07-1.38), 1.07 (95% CI 1.00-1.13) and 1.19 (95% CI 1.00-1.41), respectively. Significantly increased risk of acute lymphoblastic leukaemia associated with GSTM1 and GSTT1 null genotypes was observed. Their pooled ORs were 1.24 (95% CI 1.17-1.31) and 1.30 (95% CI 1.06-1.60), respectively. We also found substantial evidence of heterogeneity between the studies. Our results suggest that GSTM1 and GSTT1, but not GSTP1 polymorphisms, appear to be associated with a modest increase in the risk of acute lymphoblastic leukaemia. It is conceivable that GSTM1 and GSTT1 null genotypes may thus play a role in leukemogenesis. A review of the 30 case-control studies indicates that greater attention should be paid to the design of future studies.
Topics: Acute Disease; Genotype; Glutathione S-Transferase pi; Glutathione Transferase; Humans; Isoenzymes; Odds Ratio; Polymorphism, Genetic; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Risk Factors
PubMed: 15862746
DOI: 10.1016/j.ejca.2005.01.014 -
Genetics in Medicine : Official Journal... Mar 2017In 2009, the agalsidase beta shortage resulted in switching to agalsidase alfa treatment for many Fabry disease patients, offering the unique opportunity to compare the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
In 2009, the agalsidase beta shortage resulted in switching to agalsidase alfa treatment for many Fabry disease patients, offering the unique opportunity to compare the effects of the two drugs. Because single studies describing effects of switching on the disease course are limited and inconclusive, we performed a systematic review and meta-analysis of existing data.
METHODS
Relevant studies were identified in the PubMed, Cochrane, ISI Web, and SCOPUS databases from July 2009 to September 2015. The following parameters were analyzed: clinical events, changes in organ function or structure, disease-related symptoms, lyso-Gb3 plasma levels, and adverse effects.
CONCLUSIONS
The nine studies (217 patients) included in our systematic review showed only marginal differences in most of the evaluated parameters. Seven of these studies were included in the meta-analysis (176 patients). The pooled incidence rate of major adverse events was reported for five studies (150 patients) and was equal to 0.04 events per person-year. No significant change was observed after the shift in glomerular filtration rate, whereas left ventricular mass index, left ventricular posterior wall dimension, and ejection fraction were significantly reduced over time. Our data showed that the switch to agalsidase alfa was well tolerated and associated with stable clinical conditions.Genet Med 19 3, 275-282.
Topics: Disease Progression; Enzyme Replacement Therapy; Fabry Disease; Female; Glomerular Filtration Rate; Glycolipids; Humans; Isoenzymes; Male; Recombinant Proteins; Sphingolipids; Treatment Outcome; alpha-Galactosidase
PubMed: 27608175
DOI: 10.1038/gim.2016.117 -
Animals : An Open Access Journal From... Sep 2020Adiponectin is an abundant plasma protein that is closely related to obesity and obesity-related pathologies. The molecule can be found in three different isoforms, each...
Adiponectin is an abundant plasma protein that is closely related to obesity and obesity-related pathologies. The molecule can be found in three different isoforms, each with different biological activities. Studies on canine obesity have suggested that adiponectin concentrations are decreased in obesity; however, no canine meta-analyses have been performed that feature all the required data. The aim of this study is to perform a systematic review and meta-analysis of studies that pertain to total and high molecular weight (HMW) adiponectin in relation to canine obesity. From 20 different studies, a total of 366 dogs with obesity and 349 normal weight dogs are included in the meta-analysis. Client-owned dogs were most represented, accounting for 54.3% of the dogs used, while experimental dogs enrolled in the studies made up the remaining 45.7%. The concentrations of total adiponectin in dogs with obesity were significantly lower compared with normal weight dogs. Additionally, adiponectin concentrations were significantly higher in dogs after a successful weight loss protocol compared to the start of the protocol and were significantly lower in dogs after gaining weight. In conclusion, although caution should be taken due to the relatively low number of studies that exist and the high heterogeneity between them, this meta-analysis indicates that adiponectin is decreased in obese dogs.
PubMed: 32937899
DOI: 10.3390/ani10091650 -
Neuroscience and Biobehavioral Reviews May 2022Once considered only scaffolding proteins at glutamatergic postsynaptic density (PSD), Homer1 proteins are increasingly emerging as multimodal adaptors that integrate... (Review)
Review
The Homer1 family of proteins at the crossroad of dopamine-glutamate signaling: An emerging molecular "Lego" in the pathophysiology of psychiatric disorders. A systematic review and translational insight.
Once considered only scaffolding proteins at glutamatergic postsynaptic density (PSD), Homer1 proteins are increasingly emerging as multimodal adaptors that integrate different signal transduction pathways within PSD, involved in motor and cognitive functions, with putative implications in psychiatric disorders. Regulation of type I metabotropic glutamate receptor trafficking, modulation of calcium signaling, tuning of long-term potentiation, organization of dendritic spines' growth, as well as meta- and homeostatic plasticity control are only a few of the multiple endocellular and synaptic functions that have been linked to Homer1. Findings from preclinical studies, as well as genetic studies conducted in humans, suggest that both constitutive (Homer1b/c) and inducible (Homer1a) isoforms of Homer1 play a role in the neurobiology of several psychiatric disorders, including psychosis, mood disorders, neurodevelopmental disorders, and addiction. On this background, Homer1 has been proposed as a putative novel target in psychopharmacological treatments. The aim of this review is to summarize and systematize the growing body of evidence on Homer proteins, highlighting the role of Homer1 in the pathophysiology and therapy of mental diseases.
Topics: Carrier Proteins; Dopamine; Glutamates; Homer Scaffolding Proteins; Humans; Mental Disorders; Signal Transduction
PubMed: 35248676
DOI: 10.1016/j.neubiorev.2022.104596 -
Frontiers in Pharmacology 2022The nine membrane-delimited eukaryotic adenylyl cyclases are pseudoheterodimers with an identical domain order of seven (nine) distinct subdomains. Bioinformatics show...
The nine membrane-delimited eukaryotic adenylyl cyclases are pseudoheterodimers with an identical domain order of seven (nine) distinct subdomains. Bioinformatics show that the protein evolved from a monomeric bacterial progenitor by gene duplication and fusion probably in a primordial eukaryotic cell around 1.5 billion years ago. Over a timespan of about 1 billion years, the first fusion product diverged into nine highly distinct pseudoheterodimeric isoforms. The evolutionary diversification ended approximately 0.5 billion years ago because the present isoforms are found in the living fossil coelacanth, a fish. Except for the two catalytic domains, C1 and C2, the mAC isoforms are fully diverged. Yet, within each isoform a high extent of conservation of respective subdomains is found. This applies to the C- and N-termini, a long linker region between the protein halves (C1b), two short cyclase-transducing-elements (CTE) and notably to the two hexahelical membrane domains TM1 and TM2. Except for the membrane anchor all subdomains were previously implicated in regulatory modalities. The bioinformatic results unequivocally indicate that the membrane anchors must possess an important regulatory function specifically tailored for each mAC isoform.
PubMed: 36238545
DOI: 10.3389/fphar.2022.1009797 -
International Journal of Molecular... Aug 2018Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal types of tumours, and its incidence is rising worldwide. Although survival can be improved by surgical... (Review)
Review
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal types of tumours, and its incidence is rising worldwide. Although survival can be improved by surgical resection when these tumours are detected at an early stage, this cancer is usually asymptomatic, and disease only becomes apparent after metastasis. Several risk factors are associated with this disease, the most relevant being chronic pancreatitis, diabetes, tobacco and alcohol intake, cadmium, arsenic and lead exposure, certain infectious diseases, and the mutational status of some genes associated to a familial component. PDAC incidence has increased in recent decades, and there are few alternatives for chemotherapeutic treatment. Endoplasmic reticulum (ER) stress factors such as GRP78/BiP (78 kDa glucose-regulated protein), ATF6α (activating transcription factor 6 isoform α), IRE1α (inositol-requiring enzyme 1 isoform α), and PERK (protein kinase RNA-like endoplasmic reticulum kinase) activate the transcription of several genes involved in both survival and apoptosis. Some of these factors aid in inducing a non-proliferative state in cancer called dormancy. Modulation of endoplasmic reticulum stress could induce dormancy of tumour cells, thus prolonging patient survival. In this systematic review, we have compiled relevant results concerning those endoplasmic reticulum stress factors involved in PDAC, and we have analysed the mechanism of dormancy associated to endoplasmic reticulum stress and its potential use as a chemotherapeutic target against PDAC.
Topics: Activating Transcription Factor 6; Animals; Antibodies; Carcinoma, Pancreatic Ductal; Communicable Diseases; Deoxycytidine; Diabetes Complications; Disease Models, Animal; Endoplasmic Reticulum Chaperone BiP; Endoplasmic Reticulum Stress; Endoribonucleases; Gene Expression Regulation; Heat-Shock Proteins; Humans; Pancreatic Neoplasms; Pancreatitis, Chronic; Protein Serine-Threonine Kinases; RNA, Small Interfering; Risk Factors; Sulfones; eIF-2 Kinase; Gemcitabine
PubMed: 30134550
DOI: 10.3390/ijms19092468 -
Frontiers in Aging Neuroscience 2022Because of high prevalence of Alzheimer's disease (AD) in low- and middle-income countries (LMICs), there is an urgent need for inexpensive and minimally invasive...
BACKGROUND
Because of high prevalence of Alzheimer's disease (AD) in low- and middle-income countries (LMICs), there is an urgent need for inexpensive and minimally invasive diagnostic tests to detect biomarkers in the earliest and asymptomatic stages of the disease. Blood-based biomarkers are predicted to have the most impact for use as a screening tool and predict the onset of AD, especially in LMICs. Furthermore, it has been suggested that panels of markers may perform better than single protein candidates.
METHODS
Medline/Pubmed was searched to identify current relevant studies published from January 2016 to December 2020. We included all full-text articles examining blood-based biomarkers as a set of protein markers or panels to aid in AD's early diagnosis, prognosis, and characterization.
RESULTS
Seventy-six articles met the inclusion criteria for systematic review. Majority of the studies reported plasma and serum as the main source for biomarker determination in blood. Protein-based biomarker panels were reported to aid in AD diagnosis and prognosis with better accuracy than individual biomarkers. Conventional (amyloid-beta and tau) and neuroinflammatory biomarkers, such as amyloid beta-42, amyloid beta-40, total tau, phosphorylated tau-181, and other tau isoforms, were the most represented. We found the combination of amyloid beta-42/amyloid beta-40 ratio and APOEε4 status to be most represented with high accuracy for predicting amyloid beta-positron emission tomography status.
CONCLUSION
Assessment of Alzheimer's disease biomarkers in blood as a non-invasive and cost-effective alternative will potentially contribute to early diagnosis and improvement of therapeutic interventions. Given the heterogeneous nature of AD, combination of markers seems to perform better in the diagnosis and prognosis of the disease than individual biomarkers.
PubMed: 35360215
DOI: 10.3389/fnagi.2022.683689 -
Medicine Sep 2015The prognostic value of hypoxia-inducible factor (HIF) in renal cell carcinoma (RCC) has been evaluated in a large number of studies, but the reports were inconsistent... (Meta-Analysis)
Meta-Analysis Review
The prognostic value of hypoxia-inducible factor (HIF) in renal cell carcinoma (RCC) has been evaluated in a large number of studies, but the reports were inconsistent and remained inconclusive. Therefore, we conducted a systematic review and meta-analysis to clarify the significance of HIF expression in RCC prognosis. PubMed, Embase, Web of Science, Cochrane Library, EBSCO, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Biological Abstracts were searched for eligible studies. Hazard ratio (HR) data for overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS) with 95% confidence interval (CI) related to the expression status of HIF-1α or HIF-2α detected by immunohistochemistry were all extracted. Data were combined using a random- or fixed-effects model based on the corresponding inter-study heterogeneity. Subgroup analyses were also performed. A total of 14 studies composed of 1258 patients for HIF-1α evaluation and 619 patients for HIF-2α evaluation were included for further analysis. When initially analyzed as a whole, the HIF-1α expression was not significantly correlated with OS (HR 1.637, 95% CI 0.898-2.985, P = 0.108), CSS (HR 1.110, 95% CI 0.595-2.069, P = 0.744), and PFS (HR 1.113, 95% CI 0.675-1.836, P = 0.674). Similarly, HIF-2α expression was not significantly correlated with CSS (HR 1.597, 95% CI 0.667-3.824, P = 0.293) and PFS (HR 0.847, 95% CI 0.566-1.266, P = 0.417). However, subgroup analyses concerning subcellular localization of HIFs revealed that the high nuclear expression of HIF-1α was significantly associated with poor OS (HR 2.014, 95% CI 1.206-3.363, P = 0.007) and the high cytoplasmic expression of HIF -2α was significantly associated with poor CSS (HR 2.356, 95% CI 1.629-3.407, P = 0.000). The increased nuclear expression of HIF-1α and cytoplasmic expression of HIF-2α indicate unfavorable prognosis in RCC patients, which may serve as biomarkers for disease management.
Topics: Basic Helix-Loop-Helix Transcription Factors; Biomarkers, Tumor; Carcinoma, Renal Cell; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Kidney Neoplasms; Prognosis; Protein Isoforms
PubMed: 26402839
DOI: 10.1097/MD.0000000000001646 -
The Tohoku Journal of Experimental... Jan 2014Pharyngolaryngeal cancer is one of the most common head and neck cancer worldwide, and the early diagnosis and prognosis prediction are still difficult because of... (Meta-Analysis)
Meta-Analysis Review
Pharyngolaryngeal cancer is one of the most common head and neck cancer worldwide, and the early diagnosis and prognosis prediction are still difficult because of lacking in reliable cell markers. Although the expression of CD44 has been reported to correlate with poor prognosis of pharyngolaryngeal cancer in most literatures, some controversies still exist. Since the limited patient numbers within independent studies, here we performed a meta-analysis to clarify the correlations between CD44 expression and clinicopathological features and prognosis in pharyngolaryngeal cancer. A search of PubMed, ISI Web of Science and China National Knowledge Infrastructure databases (up to June 2013) was performed. Nineteen studies with 1,405 patients met the inclusion criteria. The expression of pan-CD44, including all variant isoforms, was detected in 58.0% (14.1-79.2%) specimens, while CD44-v6 (variant isoform 6 of CD44) was expressed in 54.8% (12-79.2%). In pooled analysis, CD44 expression was significantly associated with larger tumor size (T category, RR (relative risk) = 1.21, 95% CI: 1.01-1.46), lymph nodes metastasis (N category, RR = 1.94, 95% CI: 1.38-2.73) and poor prognosis [3-year overall survival (OS): RR = 0.70, 95% CI: 0.53-0.91; 5-year OS: RR = 0.66, 95% CI: 0.66-0.94]. In the stratified analysis of CD44 isoforms, high expression of CD44-v6 was related with a poor 5-year OS rate (RR = 0.53, 95% CI: 0.37-077). We propose that CD44 expression is associated with tumor size, lymph node metastasis, and poor prognosis in pharyngolaryngeal cancer patients.
Topics: Carcinoma, Squamous Cell; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Hyaluronan Receptors; Laryngeal Neoplasms; Lymphatic Metastasis; Neoplasm Metastasis; Observational Studies as Topic; Pharyngeal Neoplasms; Prognosis; Protein Isoforms; Randomized Controlled Trials as Topic; Risk; Survival Analysis; Treatment Outcome
PubMed: 24429392
DOI: 10.1620/tjem.232.9