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Molecular Pain 2021Trigeminal neuralgia (TN) is a severe facial pain disease of unknown cause and unclear genetic background. To examine the existing knowledge about genetics in TN, we...
Trigeminal neuralgia (TN) is a severe facial pain disease of unknown cause and unclear genetic background. To examine the existing knowledge about genetics in TN, we performed a systematic study asking about the prevalence of familial trigeminal neuralgia, and which genes that have been identified in human TN studies and in animal models of trigeminal pain. MedLine, Embase, Cochrane Library and Web of Science were searched from inception to January 2021. 71 studies were included in the systematic review. Currently, few studies provide information about the prevalence of familial TN; the available evidence indicates that about 1-2% of TN cases have the familial form. The available human studies propose the following genes to be possible contributors to development of TN: CACNA1A, CACNA1H, CACNA1F, KCNK1, TRAK1, SCN9A, SCN8A, SCN3A, SCN10A, SCN5A, NTRK1, GABRG1, MPZ gene, MAOA gene and SLC6A4. Their role in familial TN still needs to be addressed. The experimental animal studies suggest an emerging role of genetics in trigeminal pain, though the animal models may be more relevant for trigeminal neuropathic pain than TN per se. In summary, this systematic review suggests a more important role of genetic factors in TN pathogenesis than previously assumed.
Topics: Animals; Facial Pain; Humans; NAV1.7 Voltage-Gated Sodium Channel; Serotonin Plasma Membrane Transport Proteins; Trigeminal Neuralgia
PubMed: 34000891
DOI: 10.1177/17448069211016139 -
CNS Drugs Nov 2022For decades, treatment of mood disorders, psychoses, anxiety and dementia have been confounded by limited efficacy and high rates of treatment resistance. Preclinical... (Meta-Analysis)
Meta-Analysis
BACKGROUND
For decades, treatment of mood disorders, psychoses, anxiety and dementia have been confounded by limited efficacy and high rates of treatment resistance. Preclinical and clinical evidence have highlighted disruption of cholinergic signalling in several neuropsychiatric conditions and examined intervention strategies including acetylcholinesterase inhibitors and nicotinic receptor-targeted intervention. However, the effectiveness of these approaches is often curtailed by on-target side effects. Post mortem studies implicate muscarinic receptor dysregulation in neuropsychiatric pathophysiology; therefore, we conducted a systematic review and meta-analysis to investigate the therapeutic efficacy and safety of muscarinic receptor-targeted interventions in adults with neuropsychiatric disorders.
METHODS
PubMed, EMBASE, PsycINFO, EBSCO and Web of Science were searched using relevant keywords from database inception to 7 August 2022. Randomised, double-blind, placebo-controlled studies were included if they investigated the effect of muscarinic receptor-targeted intervention in adults with a diagnosis of a neuropsychiatric disorder and were published in English. A narrative synthesis approach was adopted to describe the findings. Wherever three or more studies with a similar intervention were available, effect sizes were calculated, and a meta-analysis was performed. Cochrane risk-of-bias-2 tool was utilised to assess the risk of bias, and sensitivity analyses were performed to identify publication bias. Certainty analysis (high, moderate, low and/or very low) was conducted using GRADE criteria.
RESULTS
Overall, 33 studies met the inclusion criteria and 5 were included in the meta-analysis. Despite a limited pool with several different interventions, we found therapeutic efficacy of xanomeline (M/M agonist) in primary psychotic disorders plus behavioural and psychological symptoms of dementia. Scopolamine showed a significant antidepressant effect in a combined cohort of major depressive and bipolar disorders in the short-term outcome measure, but no effect following cessation of treatment. Results from bias assessments suggest "very low" certainty in the antidepressant effect of scopolamine. Critical limitations of the current literature included low power, high heterogeneity in the patient population and a lack of active comparators.
CONCLUSION
While the results are not definitive, findings on muscarinic receptor-targeted interventions in several mental disorders are promising in terms of efficacy and safety, specifically in treating schizophrenia, mood disorders, and behavioural and psychiatric symptoms of Alzheimer's disease. However, orthosteric muscarinic receptor-targeted interventions are associated with a range of peripheral adverse effects that are thought to be mediated via M/M receptors. The orthosteric binding site of muscarinic acetylcholine receptors is remarkably conserved, posing a challenge for subtype-selective interventions; nonetheless allosteric ligands with biased signalling pathways are now in development. We conclude that adequately powered prospective studies with subtype-selective interventions are required to determine the clinical effectiveness of muscarinic-receptor targeted interventions for the treatment of neuropsychiatric disorders.
Topics: Adult; Humans; Depressive Disorder, Major; Prospective Studies; Acetylcholinesterase; Treatment Outcome; Antidepressive Agents; Receptors, Muscarinic; Scopolamine Derivatives; Dementia; Randomized Controlled Trials as Topic
PubMed: 36269510
DOI: 10.1007/s40263-022-00964-8 -
Medicina (Kaunas, Lithuania) May 2021: The aim of this systematic review is to summarize the current data about the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its entry... (Meta-Analysis)
Meta-Analysis Review
: The aim of this systematic review is to summarize the current data about the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its entry factors in oral tissues and cells. : This systematic review was carried out based on the Preferred Reporting Items for a Systematic Review and Meta-Analysis (PRISMA). Three databases were analyzed (Pubmed, Web of science and Scopus) by three independent researchers. From the 18 identified studies, 10 of them met the inclusion criteria. The presence of SARS-CoV-2 or its entry factors (angiotensin-converting enzyme II (ACE2), transmembrane serine proteases (TMPRSS), and furin) was analyzed in these 10 studies during the pandemic. ACE2 expression was analyzed in 9 of the 10 studies. ACE2 is expressed mainly in the tongue, oral mucosa, salivary glands and epithelial cells. The expression of the TMPRSS2 gene or protein was analyzed in 6 studies. These studies reported that the expression of TMPRSS2 was mainly in the salivary glands, tongue, sulcular epithelium and oral mucosa; as well as in cells of the salivary glands (ductal, acinar and myoepithelial cells) and the tongue (the spinous-based cell layer, horny layer and the epithelial surface). Other TMPRSS were also reported. The expression of TMPRSS3, TMPRSS4, TMPRSS5, TMPRSS7 and TMPRSS11D was reported mainly in salivary glands and in epithelial-type cells. Furan expression was analyzed in three studies. The expression of furin was detected mainly in epithelial cells of the tongue. A variety of methods were used to carry out the detection of SARS-CoV-2 or its input molecules. : These results show that SARS-CoV-2 can infect a wide variety of oral tissues and cells, and that together with the theories dedicated to explaining the oral symptoms present in SARS-CoV-2 positive patients, it provides us with a good scientific basis for understanding the virus infection in the oral cavity and its consequences.
Topics: COVID-19; Furin; Humans; Membrane Proteins; Mouth Mucosa; Neoplasm Proteins; Pandemics; SARS-CoV-2; Serine Endopeptidases
PubMed: 34070998
DOI: 10.3390/medicina57060523 -
Biomolecules Nov 2023Mitochondria are ancient endosymbiotic double membrane organelles that support a wide range of eukaryotic cell functions through energy, metabolism, and cellular... (Review)
Review
Mitochondria are ancient endosymbiotic double membrane organelles that support a wide range of eukaryotic cell functions through energy, metabolism, and cellular control. There are over 1000 known proteins that either reside within the mitochondria or are transiently associated with it. These mitochondrial proteins represent a functional subcellular protein network (mtProteome) that is encoded by mitochondrial and nuclear genomes and significantly varies between cell types and conditions. In neurons, the high metabolic demand and differential energy requirements at the synapses are met by specific modifications to the mtProteome, resulting in alterations in the expression and functional properties of the proteins involved in energy production and quality control, including fission and fusion. The composition of mtProteomes also impacts the localization of mitochondria in axons and dendrites with a growing number of neurodegenerative diseases associated with changes in mitochondrial proteins. This review summarizes the findings on the composition and properties of mtProteomes important for mitochondrial energy production, calcium and lipid signaling, and quality control in neural cells. We highlight strategies in mass spectrometry (MS) proteomic analysis of mtProteomes from cultured cells and tissue. The research into mtProteome composition and function provides opportunities in biomarker discovery and drug development for the treatment of metabolic and neurodegenerative disease.
Topics: Humans; Proteome; Neurodegenerative Diseases; Proteomics; Mitochondria; Neurons; Mitochondrial Proteins
PubMed: 38002320
DOI: 10.3390/biom13111638 -
Journal of Sport and Health Science Mar 2024One of the pathological hallmarks distinguishing Alzheimer's disease from other dementias is the accumulation of amyloid beta (Aβ). Higher physical activity is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
One of the pathological hallmarks distinguishing Alzheimer's disease from other dementias is the accumulation of amyloid beta (Aβ). Higher physical activity is associated with decreased dementia risk, and one potential path could be through Aβ levels modulation. We aimed to explore the relationship between physical activity and Aβ in middle-aged and older adults.
METHODS
A systematic search of PubMed, Web of Science, PsycINFO, Cochrane Central Register of Controlled Trials, and SPORTDiscus was performed from inception to April 28, 2022. Studies were eligible if they included physical activity and Aβ data in adults aged 45 years or older. Multi-level meta-analyses of intervention and observational studies were performed to examine the role of physical activity in modulating Aβ levels.
RESULTS
In total, 37 articles were included (8 randomized controlled trials, 3 non-randomized controlled trials, 4 prospective longitudinal studies, and 22 cross-sectional studies). The overall effect size of physical activity interventions on changes in blood Aβ was medium (pooled standardized mean difference = -0.69, 95% confidence interval (95%CI): -1.41 to 0.03; I = 74.6%). However, these results were not statistically significant, and there were not enough studies to explore the effects of physical activity on cerebrospinal fluid (CSF) and brain Aβ. Data from observational studies were examined based on measurements of Aβ in the brain using positron emission tomography scans, CSF, and blood. Higher physical activity was positively associated with Aβ only in the CSF (Estimate r = 0.12; 95%CI: 0.05-0.18; I = 38.00%).
CONCLUSION
Physical activity might moderately reduce blood Aβ in middle-aged and older adults. However, results were only near statistical significance and might be interpreted with caution given the methodological limitations observed in some of the included studies. In observational studies, higher levels of physical activity were positively associated with Aβ only in CSF. Therefore, further research is needed to understand the modulating role of physical activity in the brain, CSF, and blood Aβ, as well as its implication for cognitive health.
Topics: Middle Aged; Humans; Aged; Amyloid beta-Peptides; Prospective Studies; Cross-Sectional Studies; Alzheimer Disease; Brain
PubMed: 37558161
DOI: 10.1016/j.jshs.2023.08.001 -
PloS One 2021GPRC5A is associated with various cancer initiation and progression. Controversial findings have been reported about GPRC5A prognostic characteristics, and no... (Meta-Analysis)
Meta-Analysis
BACKGROUND
GPRC5A is associated with various cancer initiation and progression. Controversial findings have been reported about GPRC5A prognostic characteristics, and no meta-analysis has been conducted to assess the relationship between GPRC5A and cancer prognosis. Therefore, the objective of this meta-analysis is to evaluate the overall prognostic effectiveness of GPRC5A.
METHODS
We first conducted a systematic search in the PubMed, Embase, Web of Science, CNKI, Cochrane, and WangFang databases. The hazard ratio (HR) and odds ratios (OR) with 95% CI were then pooled to assess the associations between GPRC5A expression and overall survival (OS), disease-free survival (DFS), event-free survival (EFS), and clinicopathological characteristics. Chi-squared test and I2 statistics were completed to evaluate the heterogeneity in our study. A random-effects model was used when significant heterogeneity existed (I2>50% and p<0.05); otherwise, we chose the fixed-effect model. Subgroup analysis was stratified by tumor type, region, HR obtained measurements, and sample capacity to explore the source of heterogeneity.
RESULTS
In total, 15 studies with 624 patients met inclusion criteria of this study. Our results showed that higher expression of GPRC5A is associated with worse OS (HR:1.69 95%CI: 1.20-2.38 I2 = 75.6% p = 0.000), as well as worse EFS (HR:1.45 95%CI: 1.02-1.95 I2 = 0.0% p = 0.354). Subgroup analysis indicated that tumor type might be the source of high heterogeneity. Additionally, cancer patients with enhanced GPRC5A expression were more likely to lymph node metastasis (OR:1.95, 95%CI 1.33-2.86, I2 = 43.9%, p = 0.129) and advanced tumor stage (OR: 1.83, 95%CI 1.15-2.92, I2 = 61.3%, p = 0.035), but not associated with age, sex, differentiation, and distant metastasis.
CONCLUSION
GPRC5A can be a promising candidate for predicting medical outcomes and used for accurate diagnosis, prognosis prediction for patients with cancer; however, the predictive value of GPRC5A varies significantly according to cancer type. Further studies for this mechanism will be necessary to reveal novel insights into application of GPRC5A in cancers.
Topics: Disease-Free Survival; Humans; Neoplasms; Prognosis; Progression-Free Survival; Publication Bias; Receptors, G-Protein-Coupled
PubMed: 33788883
DOI: 10.1371/journal.pone.0249040 -
International Journal of Surgery... Nov 2023Hepatocellular carcinoma (HCC) is the third-most lethal malignant tumor worldwide. The rapid development of immunotherapy utilizing immune checkpoint inhibitors for... (Meta-Analysis)
Meta-Analysis
Clinico-characteristics of patients which correlated with preferable treatment outcomes in immunotherapy for advanced hepatocellular carcinoma: a systematic review and meta-analysis.
BACKGROUND AND AIMS
Hepatocellular carcinoma (HCC) is the third-most lethal malignant tumor worldwide. The rapid development of immunotherapy utilizing immune checkpoint inhibitors for advanced HCC patients has been witnessed in recent years, along with numerous randomized clinical trials demonstrating the survival benefits for these individuals. This systematic review and meta-analysis aimed to identify specific clinico-pathological characteristics of advanced HCC patients that may lead to preferable responses to immunotherapy in terms of overall survival (OS), progression-free survival (PFS), and objective response rate (ORR).
METHODS
The included clinical trials were retrieved from PubMed, Embase, the Cochrane library, and the Web of Science databases published in English between 1 January 2002 and 20 October 2022. A systematic review and meta-analysis for first-line and second-line phase II/III studies were conducted on immunotherapy for patients with advanced HCC by using OS as the primary outcome measure, and PFS and ORR as the secondary outcome measures to obtain clinico-pathological characteristics of patients which might be preferable responses to programmed death-1 (PD-1) and programmed cell death-Ligand 1 (PD-L1) inhibitors. Toxicity and specific treatment-related adverse events (TRAEs) were also determined.
RESULTS
After screening 1392 relevant studies, 12 studies were included in this systematic review and meta-analysis to include 5948 patients. Based on the analysis of interaction, the difference in OS after first-line immunotherapy between the subgroups of viral hepatitis [hazard ratio (HR)=0.73 vs 0.87, P for interaction=0.02] and macrovascular invasion and/or extrahepatic spread (HR=0.73 vs 0.89, P for interaction=0.02) were significant. The difference in PFS between the subgroups of viral hepatitis was highly significant (pooled HR=0.55 vs 0.81, P for interaction=0.007). After second-line immunotherapy, the difference in ORR between the subgroups of Barcelona Clinic Liver Cancer was significant (pooled ES=0.12 vs 0.23, P for interaction=0.04). Compared with PD-L1 inhibitors, PD-1 inhibitors may have a higher probability to cause TRAEs. Diarrhea, increased aspartate aminotransferase, and hypertension were the top three TRAEs.
CONCLUSIONS
This systematic review and meta-analysis represents the first pilot study aimed at identifying crucial clinico-pathological characteristics of patients with advanced HCC that may predict favorable treatment outcomes in terms of OS, PFS, and ORR to immunotherapy. Findings suggest that patients with viral hepatitis positivity (especially hepatitis B virus) and macrovascular invasion and/or extrahepatic spread may benefit more in OS when treated with PD-1/PD-L1 immune checkpoint inhibitors.
Topics: Humans; Carcinoma, Hepatocellular; B7-H1 Antigen; Immune Checkpoint Inhibitors; Pilot Projects; Programmed Cell Death 1 Receptor; Liver Neoplasms; Treatment Outcome; Immunotherapy; Hepatitis, Viral, Human; Lung Neoplasms
PubMed: 37598406
DOI: 10.1097/JS9.0000000000000652 -
Journal of Clinical Medicine Dec 2022Fatty acid translocase/cluster of differentiation 36 (FAT/CD36) is a multifunctional membrane protein activated by a high-fat diet, physical exercise, fatty acids (FAs),... (Review)
Review
Fatty acid translocase/cluster of differentiation 36 (FAT/CD36) is a multifunctional membrane protein activated by a high-fat diet, physical exercise, fatty acids (FAs), leptin, and insulin. The principal function of FAT/CD36 is to facilitate the transport of long-chain fatty acids through cell membranes such as myocytes, adipocytes, heart, and liver. Under high-energy expenditure, the different isoforms of FAT/CD36 in the plasma membrane and mitochondria bind to the mobilization and oxidation of FAs. Furthermore, FAT/CD36 is released in its soluble form and becomes a marker of metabolic dysfunction. Studies with healthy animals and humans show that physical exercise and a high-lipid diet increase FAT/CD36 expression and caloric expenditure. However, several aspects such as obesity, diabetes, Single Nucleotide polymorphisms (SNPs), and oxidative stress affect the normal FAs metabolism and function of FAT/CD36, inducing metabolic disease. Through a comprehensive systematic review of primary studies, this work aimed to document molecular mechanisms related to FAT/CD36 in FAs oxidation and trafficking in skeletal muscle under basal conditions, physical exercise, and diet in healthy individuals.
PubMed: 36615118
DOI: 10.3390/jcm12010318 -
Clinical and Molecular Hepatology Apr 2023Hepatocellular carcinoma (HCC) is one of the most common and deadly cancers worldwide and is characterized by complex molecular carcinogenesis. Neuropilins (NRPs) NRP1... (Review)
Review
Hepatocellular carcinoma (HCC) is one of the most common and deadly cancers worldwide and is characterized by complex molecular carcinogenesis. Neuropilins (NRPs) NRP1 and NRP2 are the receptors of multiple proteins involved in key signaling pathways associated with tumor progression. We aimed to systematically review all the available findings on their role in HCC. We searched the Scopus, Web of Science (WOS), PubMed, Cochrane and Embase databases for articles evaluating NRPs in preclinical or clinical HCC models. This study was registered in PROSPERO (CRD42022349774) and include 49 studies. Multiple cellular and molecular processes have been associated with one or both NRPs, indicating that they are potential diagnostic and prognostic biomarkers in HCC patients. Mainly NRP1 has been shown to promote tumor cell survival and progression by modulating several signaling pathways. NRPs mainly regulate angiogenesis, invasion and migration and have shown to induce invasion and metastasis. They also regulate the immune response and tumor microenvironment, showing a crucial interplay with the hypoxia response and microRNAs in HCC. Altogether, NRP1 and NRP2 are potential biomarkers and therapeutic targets, providing novel insight into the clinical landscape of HCC patients.
Topics: Humans; Carcinoma, Hepatocellular; Neuropilins; Liver Neoplasms; Signal Transduction; Biomarkers; Biomarkers, Tumor; Tumor Microenvironment
PubMed: 36726054
DOI: 10.3350/cmh.2022.0425 -
Frontiers in Cellular and Infection... 2023Identifying novel biomarkers that are both specific and sensitive to periprosthetic joint infection (PJI) has the potential to improve diagnostic accuracy and ultimately... (Review)
Review
BACKGROUND
Identifying novel biomarkers that are both specific and sensitive to periprosthetic joint infection (PJI) has the potential to improve diagnostic accuracy and ultimately enhance patient outcomes. Therefore, the aim of this systematic review is to identify and evaluate the effectiveness of novel biomarkers for the diagnosis of PJI.
METHODS
We searched the MEDLINE, EMBASE, PubMed, and Cochrane Library databases from January 1, 2018, to September 30, 2022, using the search terms "periprosthetic joint infection," "prosthetic joint infection," or "periprosthetic infection" as the diagnosis of interest and the target index, combined with the term "marker." We excluded articles that mentioned established biomarkers such as CRP, ESR, Interleukin 6, Alpha defensin, PCT (procalcitonin), and LC (leucocyte cell count). We used the MSIS, ICM, or EBJS criteria for PJI as the reference standard during quality assessment.
RESULTS
We collected 19 studies that analyzed fourteen different novel biomarkers. Proteins were the most commonly analyzed biomarkers (nine studies), followed by molecules (three studies), exosomes (two studies), DNA (two studies), interleukins (one study), and lysosomes (one study). Calprotectin was a frequently analyzed and promising marker. In the scenario where the threshold was set at ≥50-mg/mL, the calprotectin point-of-care (POC) performance showed a high sensitivity of 98.1% and a specificity of 95.7%.
CONCLUSION
None of the analyzed biomarkers demonstrated outstanding performance compared to the established parameters used for standardized treatment based on established PJI definitions. Further studies are needed to determine the benefit and usefulness of implementing new biomarkers in diagnostic PJI settings.
Topics: Humans; Prosthesis-Related Infections; Arthritis, Infectious; Biomarkers; Procalcitonin; Leukocyte Count; alpha-Defensins; Sensitivity and Specificity
PubMed: 37529352
DOI: 10.3389/fcimb.2023.1210345