-
Signal Transduction and Targeted Therapy Oct 2020Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging virus that is highly pathogenic and has caused the recent worldwide pandemic officially named...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging virus that is highly pathogenic and has caused the recent worldwide pandemic officially named coronavirus disease (COVID-19). Currently, considerable efforts have been put into developing effective and safe drugs and vaccines against SARS-CoV-2. Vaccines, such as inactivated vaccines, nucleic acid-based vaccines, and vector vaccines, have already entered clinical trials. In this review, we provide an overview of the experimental and clinical data obtained from recent SARS-CoV-2 vaccines trials, and highlight certain potential safety issues that require consideration when developing vaccines. Furthermore, we summarize several strategies utilized in the development of vaccines against other infectious viruses, such as severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), with the aim of aiding in the design of effective therapeutic approaches against SARS-CoV-2.
Topics: Angiotensin-Converting Enzyme 2; Antibodies, Viral; Betacoronavirus; COVID-19; COVID-19 Vaccines; Clinical Trials as Topic; Coronavirus Infections; Gene Expression Regulation; Humans; Immunity, Innate; Immunization Schedule; Immunogenicity, Vaccine; Middle East Respiratory Syndrome Coronavirus; Pandemics; Patient Safety; Peptidyl-Dipeptidase A; Pneumonia, Viral; Protein Binding; Receptors, Virus; Severe acute respiratory syndrome-related coronavirus; SARS-CoV-2; Severe Acute Respiratory Syndrome; Spike Glycoprotein, Coronavirus; Vaccines, Attenuated; Vaccines, DNA; Vaccines, Subunit; Vaccines, Virus-Like Particle; Viral Vaccines
PubMed: 33051445
DOI: 10.1038/s41392-020-00352-y -
Molecular Psychiatry Jul 2023Impairment of insulin action and metabolic dysregulation have traditionally been associated with schizophrenia, although the molecular basis of such association remains... (Meta-Analysis)
Meta-Analysis
Impairment of insulin action and metabolic dysregulation have traditionally been associated with schizophrenia, although the molecular basis of such association remains still elusive. The present meta-analysis aims to assess the impact of insulin action manipulations (i.e., hyperinsulinemia, hypoinsulinemia, systemic or brain insulin resistance) on glutamatergic, dopaminergic, γ-aminobutyric acid (GABA)ergic, and serotonergic pathways in the central nervous system. More than one hundred outcomes, including transcript or protein levels, kinetic parameters, and other components of the neurotransmitter pathways, were collected from cultured cells, animals, or humans, and meta-analyzed by applying a random-effects model and adopting Hedges'g to compare means. Two hundred fifteen studies met the inclusion criteria, of which 180 entered the quantitative synthesis. Significant impairments in key regulators of synaptic plasticity processes were detected as the result of insulin handlings. Specifically, protein levels of N-methyl-D-aspartate receptor (NMDAR) subunits including type 2A (NR2A) (Hedges' g = -0.95, 95%C.I. = -1.50, -0.39; p = 0.001; I = 47.46%) and 2B (NR2B) (Hedges'g = -0.69, 95%C.I. = -1.35, -0.02; p = 0.043; I = 62.09%), and Postsynaptic density protein 95 (PSD-95) (Hedges'g = -0.91, 95%C.I. = -1.51, -0.32; p = 0.003; I = 77.81%) were found reduced in insulin-resistant animal models. Moreover, insulin-resistant animals showed significantly impaired dopamine transporter activity, whereas the dopamine D2 receptor mRNA expression (Hedges'g = 3.259; 95%C.I. = 0.497, 6.020; p = 0.021; I = 90.61%) increased under insulin deficiency conditions. Insulin action modulated glutamate and GABA release, as well as several enzymes involved in GABA and serotonin synthesis. These results suggest that brain neurotransmitter systems are susceptible to insulin signaling abnormalities, resembling the discrete psychotic disorders' neurobiology and possibly contributing to the development of neurobiological hallmarks of treatment-resistant schizophrenia.
Topics: Humans; Animals; Schizophrenia; Insulin; Neurobiology; Disks Large Homolog 4 Protein; Receptors, N-Methyl-D-Aspartate; gamma-Aminobutyric Acid; Neurotransmitter Agents
PubMed: 37085712
DOI: 10.1038/s41380-023-02065-4 -
Journal of Neurotrauma Apr 2021Accurate diagnosis of traumatic brain injury (TBI) is critical to effective management and intervention, but can be challenging in patients with mild TBI. A substantial... (Meta-Analysis)
Meta-Analysis
Blood-Based Protein Biomarkers for the Management of Traumatic Brain Injuries in Adults Presenting to Emergency Departments with Mild Brain Injury: A Living Systematic Review and Meta-Analysis.
Accurate diagnosis of traumatic brain injury (TBI) is critical to effective management and intervention, but can be challenging in patients with mild TBI. A substantial number of studies have reported the use of circulating biomarkers as signatures for TBI, capable of improving diagnostic accuracy and clinical decision making beyond current practice standards. We performed a systematic review and meta-analysis to comprehensively and critically evaluate the existing body of evidence for the use of blood protein biomarkers (S100 calcium binding protein B [S100B], glial fibrillary acidic protein [GFAP], neuron specific enolase [NSE], ubiquitin C-terminal hydrolase-L1 [UCH-L1]. tau, and neurofilament proteins) for diagnosis of intracranial lesions on CT following mild TBI. Effects of potential confounding factors and differential diagnostic performance of the included markers were explored. Further, appropriateness of study design, analysis, quality, and demonstration of clinical utility were assessed. Studies published up to October 2016 were identified through searches of MEDLINE, Embase, EBM Reviews, the Cochrane Library, World Health Organization (WHO), International Clinical Trials Registry Platform (ICTRP), and clinicaltrials.gov. Following screening of the identified articles, 26 were selected as relevant. We found that measurement of S100B can help informed decision making in the emergency department, possibly reducing resource use; however, there is insufficient evidence that any of the other markers is ready for clinical application. Our work pointed out serious problems in the design, analysis, and reporting of many of the studies, and identified substantial heterogeneity and research gaps. These findings emphasize the importance of methodologically rigorous studies focused on a biomarker's intended use, and defining standardized, validated, and reproducible approaches. The living nature of this systematic review, which will summarize key updated information as it becomes available, can inform and guide future implementation of biomarkers in the clinical arena.
Topics: Adult; Biomarkers; Blood Proteins; Brain Concussion; Brain Injuries, Traumatic; Disease Management; Emergency Service, Hospital; Glial Fibrillary Acidic Protein; Humans; Neurofilament Proteins; Phosphopyruvate Hydratase; S100 Calcium Binding Protein beta Subunit
PubMed: 29020853
DOI: 10.1089/neu.2017.5182 -
Pathogens (Basel, Switzerland) Nov 2023Host genetic factors significantly influence susceptibility to SARS-CoV-2 infection and COVID-19 severity. Among these genetic factors are single-nucleotide variants... (Review)
Review
Host genetic factors significantly influence susceptibility to SARS-CoV-2 infection and COVID-19 severity. Among these genetic factors are single-nucleotide variants (SNVs). and genes have been associated with severe COVID-19 in populations from the United Kingdom, Africa, and Latin America. IFNAR1 and IFNAR2 are subunits forming the type I interferon receptor (IFNAR). SNVs in the genes impact protein function, affecting antiviral response and disease phenotypes. This systematic review aimed to describe and variants associated with COVID-19 susceptibility and severity. Accordingly, the current review focused on and studies published between January 2021 and February 2023, utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) protocol. The electronic search was conducted in PubMed databases using Boolean operators and inclusion and exclusion criteria. Of the 170 literature pieces, 11 studies were included. We include case reports of rare SNVs, defined by minor allele frequency (MAF) < 1%, and genome-wide associated studies (GWAS). Variants in and could potentially be new targets for therapies that limit the infection and the resulting inflammation by SARS-CoV-2 infection.
PubMed: 38003785
DOI: 10.3390/pathogens12111320 -
Archives of Academic Emergency Medicine 2024Traumataic brain injury (TBI) represents a significant global health burden. This systematic review delves into the comparison of S100B and Neuron-Specific Enolase (NSE)... (Review)
Review
INTRODUCTION
Traumataic brain injury (TBI) represents a significant global health burden. This systematic review delves into the comparison of S100B and Neuron-Specific Enolase (NSE) regarding their diagnostic and prognostic accuracy in TBI within the adult population.
METHODS
Conducted on October 21, 2023, the search identified 24 studies encompassing 6454 adult patients. QUADAS-2 and QUAPAS tools were employed to assess the risk of bias. The analyses aimed to evaluate the diagnostic and prognostic performance of S100B and NSE based on sensitivity, specificity, and area under the curve (AUC). The outcomes were detecting intracranial injury, mortality, and unfavorable outcome.
RESULTS
Pooled data analysis tended towards favoring S100B for diagnostic and prognostic purposes. S100B exhibited a diagnostic AUC of 0.74 (95% confidence interval (CI): 0.70-0.78), sensitivity of 80% (95% CI: 63%-90%), and specificity of 59% (95% CI: 45%-72%), outperforming NSE with an AUC of 0.66 (95% CI: 0.61-0.70), sensitivity of 74% (95% CI: 53%-88%), and specificity of 46% (95% CI: 24%-69%). Notably, both biomarkers demonstrated enhanced diagnostic value when blood samples were collected within 12 hours post-injury. The analyses also revealed the excellent diagnostic ability of S100B with a sensitivity of 99% (95% CI: 4%-100%) and a specificity of 76% (95% CI: 51%-91%) in mild TBI patients (AUC = 0.89 [0.86-0.91]). In predicting mortality, S100B showed a sensitivity of 90% (95% CI: 65%-98%) and specificity of 61% (95% CI: 39%-79%), slightly surpassing NSE's performance with a sensitivity of 88% (95% CI: 76%-95%) and specificity of 56% (95% CI: 47%-65%). For predicting unfavorable outcomes, S100B exhibited a sensitivity of 83% (95% CI: 74%-90%) and specificity of 51% (95% CI: 30%-72%), while NSE had a sensitivity of 80% (95% CI: 64%-90%) and specificity of 59% (95% CI: 46%-71%).
CONCLUSION
Although neither biomarker has shown promising diagnostic performance in detecting abnormal computed tomography (CT) findings, they have displayed acceptable outcome prediction capabilities, particularly with regard to mortality.
PubMed: 38572218
DOI: 10.22037/aaem.v12i1.2222 -
The Malaysian Journal of Medical... Jun 2022The prevalence of type 2 diabetes mellitus (T2DM) is increasing among Asians. The adenosine monophosphate-activated protein kinase (AMPK) increases T2DM risk through... (Review)
Review
The prevalence of type 2 diabetes mellitus (T2DM) is increasing among Asians. The adenosine monophosphate-activated protein kinase (AMPK) increases T2DM risk through insulin resistance. Glucose levels are related to AMPK subunit α2 encoded by . This systematic review and meta-analysis aimed to analyse the association between variation and T2DM risk. Publication search related to and T2DM used PubMed, ProQuest, and ScienceDirect databases. Article selection based on inclusion and exclusion criteria only included Japanese and Chinese populations. This meta-analysis used five genotype models to estimate the effect of variation and T2DM risk. Additionally, a fixed-effect model was selected to measure the pooled size effect if > 0.05 or I < 50%. Qualitative analysis included four eligible studies, and meta-analysis included only two studies because both showed data concerning rs2746342 variation. Patients with G allele are 1.45 times more likely to have T2DM than patients with T allele (95% confidence interval [CI]: 1.20, 1.76; : 0.0001). Notably, patients who had GG genotype have 1.96 times higher risk of T2DM compared with those with TT genotype (95% CI: 1.34, 2.87; : 0.0005), dominant model (odds ratio [OR]: 1.75; 95% CI: 1.32, 2.31; : 0.001), and recessive model (OR: 1.43; 95% CI: 1.01, 2.01; : 0.04). variation, especially in rs2746342, has an association with T2DM risk in the G allele, additive, dominant, and recessive models. G allele might be the most contributable factor in increasing T2DM susceptibility.
PubMed: 35846493
DOI: 10.21315/mjms2022.29.3.2 -
Arab Journal of Urology 2021: To provide a summary of the current evaluation of azoospermia and insights into future perspectives in the evaluation and counselling of men with azoospermia. : A...
: To provide a summary of the current evaluation of azoospermia and insights into future perspectives in the evaluation and counselling of men with azoospermia. : A search of PubMed, Cochrane Reviews and Web of Science databases was performed for full-text English-language articles published between 1943 and 2020 focussing on 'future perspectives', 'azoospermia' and 'evaluation'. : Azoospermia represents a severe form of male infertility characterised by sperm production so impaired that there are no sperm present in the ejaculate. The current evaluation of azoospermia focusses on patient history and physical examination with selected adjunctive laboratory investigations including serum hormones, a karyotype and screening for Y chromosome microdeletions. Future diagnostics are focussed on identifying the underlying genetic aetiologies for azoospermia, as well as a greater emphasis on screening for systemic illness that men with severe infertility may be predisposed to develop. : Azoospermia represents an extreme form of male infertility, and evaluation relies heavily on history and physical examination, as genetic evaluations for these individuals remain limited. Future evaluation will focus on next-generation sequencing and more rigorous evaluation for possible co-existing and future risk of systemic disease. : ADGRG2, adhesion G protein-coupled receptor G2; ASRM: American Society of Reproductive Medicine; AZF: azoospermia factor; CBAVD: congenital bilateral absence of the vas deferens; CFTR: cystic fibrosis transmembrane conductance regulator; CRKL: CRK-like proto-oncogene; E2F1: E2F transcription factor 1; HAUS7: HAUS augmin-like complex subunit 7; HR: hazard ratio; KS: Klinefelter syndrome; MAZ, MYC-associated zinc finger protein; NGS: next-generation sequencing; NOA: non-obstructive azoospermia; OA: obstructive azoospermia; RHOX: reproductive homeobox on the X chromosome; SH2: SRC homology 2; TAF7L: TATA-box binding protein associated factor 7-like; TEX11: testis-expressed 11; WES: whole-exome sequencing.
PubMed: 34552771
DOI: 10.1080/2090598X.2021.1954415 -
Frontiers in Endocrinology 2022It is currently controversial whether subclinical hyperthyroidism is associated with gene variants. We describe a man with subclinical hyperthyroidism and a gene...
BACKGROUND AND OBJECTIVES
It is currently controversial whether subclinical hyperthyroidism is associated with gene variants. We describe a man with subclinical hyperthyroidism and a gene variant who was diagnosed with Carney complex (CNC), and we performed a systematic review of published studies to assess the association between gene variants and the risk of subclinical hyperthyroidism.
DESIGN AND METHODS
The PubMed, EMBASE, OVID, Science Direct, and gray literature electronic databases were searched for articles published from January 2002 to May 2021 using predefined keywords and inclusion and exclusion criteria. Data on thyroid function from selected studies were extracted and analyzed.
RESULTS
We identified a CNC patient with a subclinical hyperthyroidism phenotype combined with multiple components and genetic sequenced data. In a subsequent systematic review, twenty selected studies (14 case studies and 6 series studies) enrolling 23 individuals were included in the final analysis. The patient's thyroid function data were qualitative in 11 cases and quantitative in 12 cases. The prevalence of subclinical hyperthyroidism in the CNC patients with a gene variant, including our patient, was markedly higher than that in the normal population (12.5% vs. 2%).
CONCLUSIONS
The findings of this systematic review provide helpful evidence that gene variants and subclinical hyperthyroidism are related and suggest that subclinical hyperthyroidism may be a neglected phenotype of gene variants and a novel component of CNC patients.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO, identifier CRD42021197655.
Topics: Carney Complex; Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; Humans; Hyperthyroidism; Phenotype
PubMed: 36213268
DOI: 10.3389/fendo.2022.951133 -
Frontiers in Aging Neuroscience 2020Sarcopenia is an aging process with a decline of skeletal muscle mass and function, which is a challenging public health problem with reduced quality of life in...
Sarcopenia is an aging process with a decline of skeletal muscle mass and function, which is a challenging public health problem with reduced quality of life in patients. The endplate, the post-synaptic part of the neuromuscular junction (NMJ), occupies 0.1% of the myofiber surface area only, but is composed of millions of acetylcholine receptors (AChRs) that are efficient in binding to acetylcholine (ACh) and triggering skeletal muscle contraction. This systematic review aims to examine aging-associated alterations of post-synaptic AChRs, including morphology, function and related gene expression. A systematic literature search was conducted in PubMed, Embase and Web of Science with relevant keywords by two independent reviewers. Original pre-clinical and clinical studies regarding AChRs changes during aging with available full text and written in English were included. Information was extracted from the included studies for further review. In total, 30 articles were included. Various parameters assessing AChRs alterations by radioassay, immunofluorescence, electrophysiology and mechanical test were reported. Endplate fragmentation and denervation were common in old skeletal muscles during aging. To ensure efficient NMJ transmission and force generation, type I or IIb muscle fibers tended to have increased ACh quanta releasing after electrical stimulations, while type IIa muscle fibers tended to have stronger binding between ACh and AChRs, but the overall function of AChRs was reduced during aging. Alterations of AChRs area depended on muscle type, species and the progress of muscle atrophy and type I muscles fibers tended to demonstrate enlarging AChRs areas. Myogenic regulator factors (MRFs) can regulate the expression of AChRs subunits, while decreased MRF4 may lead to expression changes of AChRs subunits during aging. Sarcoglycan-α can delay low-density lipoprotein receptor-related protein 4 (LRP4) degradation. This protein was increased in old muscles but still cannot suppress the degradation of LRP4. Investigating the role of these AChRs-related genes in the process of aging may provide a potential target to treat sarcopenia.
PubMed: 33362532
DOI: 10.3389/fnagi.2020.597811 -
Scientific Reports Jun 2024To elucidate the correlation of HIF1A with clinicopathologic characteristics in patients with gastric cancer (GC), we conducted a systematic review and meta-analysis. We... (Meta-Analysis)
Meta-Analysis
To elucidate the correlation of HIF1A with clinicopathologic characteristics in patients with gastric cancer (GC), we conducted a systematic review and meta-analysis. We searched PubMed, Embase and Web of Science for studies on GC and HIF1A, covering studies published until January 31st, 2022. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for clinical characteristics based on high and low HIF1A protein levels. We used random-effects and fixed-effects meta-analysis methods to determine mean effect sizes of ORs and evaluated publication heterogeneity with τ, I, and Q values. Additionally, we generated funnel plots to inspect publication bias. Our meta-analysis included 20 publications with 3416 GC patients to estimate the association between high or low HIF1A expression and clinical characteristics. Positive HIF1A expression was significantly associated with T stage progression (OR: 2.46; 95% CI 1.81-3.36; P < 0.01), TNM stage progression (OR: 2.50; 95% CI 1.61-3.87; P < 0.01), lymph node metastasis (OR: 2.06; 95% CI 1.44-2.94; P < 0.01), undifferentiated status (OR: 1.83; 95% CI 1.45-2.32; P < 0.01), M stage progression (OR: 2.34; 95% CI 1.46-3.77; P < 0.01), Borrmann stage progression (OR: 1.48; 95% CI 1.02-2.15; P = 0.04), larger tumor size (OR: 1.27; 95% CI 1.06-1.52; P < 0.01), vascular invasion (OR: 1.94; 95% CI 1.38-2.72; P < 0.01), and higher vascular endothelial growth factor (VEGF) protein expression (OR: 2.61; 95% CI 1.79-3.80; P < 0.01) in our meta-analysis. GC Patients highly expressing HIF1A protein might be prone to tumor progression, poorly differentiated GC cell types, and a high VEGF expression.
Topics: Stomach Neoplasms; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Lymphatic Metastasis; Biomarkers, Tumor; Neoplasm Staging; Vascular Endothelial Growth Factor A; Gene Expression Regulation, Neoplastic
PubMed: 38877062
DOI: 10.1038/s41598-024-63019-6