-
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 -
Nutrients Nov 2021Several observational studies have examined vitamin D pathway polymorphisms and their association with type 1 diabetes (T1D) susceptibility, with inconclusive results.... (Meta-Analysis)
Meta-Analysis
Several observational studies have examined vitamin D pathway polymorphisms and their association with type 1 diabetes (T1D) susceptibility, with inconclusive results. We aimed to perform a systematic review and meta-analysis assessing associations between selected variants affecting 25-hydroxyvitamin D [25(OH)D] and T1D risk. We conducted a systematic search of Medline, Embase, Web of Science and OpenGWAS updated in April 2021. The following keywords "vitamin D" and/or "single nucleotide polymorphisms (SNPs)" and "T1D" were selected to identify relevant articles. Seven SNPs (or their proxies) in six genes were analysed: rs10741657, (low frequency) rs117913124, rs12785878, rs3755967, rs17216707, rs10745742 and rs8018720. Seven case-control and three cohort studies were eligible for quantitative synthesis ( = 10). Meta-analysis results suggested no association with T1D (range of pooled ORs for all SNPs: 0.97-1.02; > 0.01). Heterogeneity was found in rs12785878 (I: 64.8%, = 0.02). Sensitivity analysis showed exclusion of any single study did not alter the overall pooled effect. No association with T1D was observed among a Caucasian subgroup. In conclusion, the evidence from the meta-analysis indicates a null association between selected variants affecting serum 25(OH)D concentrations and T1D.
Topics: Adolescent; Adult; Amidohydrolases; Carbon-Nitrogen Ligases with Glutamine as Amide-N-Donor; Child; Child, Preschool; Cholestanetriol 26-Monooxygenase; Cohort Studies; Cytochrome P450 Family 2; Diabetes Mellitus, Type 1; Female; Genetic Predisposition to Disease; Humans; Male; Oxidoreductases Acting on CH-CH Group Donors; Polymorphism, Single Nucleotide; Receptors, Calcitriol; Vesicular Transport Proteins; Vitamin D; Vitamin D Deficiency; Vitamin D-Binding Protein; Vitamin D3 24-Hydroxylase; Young Adult
PubMed: 34959812
DOI: 10.3390/nu13124260 -
Cancers Jul 2020Aquaporin (AQP) channels enable regulated transport of water and solutes essential for fluid homeostasis, but they are gaining attention as targets for anticancer...
Aquaporin (AQP) channels enable regulated transport of water and solutes essential for fluid homeostasis, but they are gaining attention as targets for anticancer therapies. Patterns of AQP expression and survival rates for patients were evaluated by systematic review (PubMed and Embase) and transcriptomic analyses of RNAseq data (Human Protein Atlas database). Meta-analyses confirmed predominantly negative associations between AQP protein and RNA expression levels and patient survival times, most notably for AQP1 in lung, breast and prostate cancers; AQP3 in esophageal, liver and breast cancers; and AQP9 in liver cancer. Patterns of AQP expression were clustered for groups of cancers and associated with risk of death. A quantitative transcriptomic analysis of AQP1-10 in human cancer biopsies similarly showed that increased transcript levels of AQPs 1, 3, 5 and 9 were most frequently associated with poor survival. Unexpectedly, increased AQP7 and AQP8 levels were associated with better survival times in glioma, ovarian and endometrial cancers, and increased AQP11 with better survival in colorectal and breast cancers. Although molecular mechanisms of aquaporins in pathology or protection remain to be fully defined, results here support the hypothesis that overexpression of selected classes of AQPs differentially augments cancer progression. Beyond fluid homeostasis, potential roles for AQPs in cancers (suggested from an expanding appreciation of their functions in normal tissues) include cell motility, membrane process extension, transport of signaling molecules, control of proliferation and apoptosis, increased mechanical compliance, and gas exchange. AQP expression also has been linked to differences in sensitivity to chemotherapy treatments, suggesting possible roles as biomarkers for personalized treatments. Development of AQP pharmacological modulators, administered in cancer-specific combinations, might inspire new interventions for controlling malignant carcinomas.
PubMed: 32679804
DOI: 10.3390/cancers12071911 -
Lipids in Health and Disease Sep 2023Hepatitis C has been associated with the development of hepatic steatosis, which increases the risk of liver cancer. The microsomal triglyceride transporter protein... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hepatitis C has been associated with the development of hepatic steatosis, which increases the risk of liver cancer. The microsomal triglyceride transporter protein (MTTP), is a lipid transport protein that mediates lipid metabolism and CD1d antigen presentation. The study aimed to explore the association between MTTP genotype (-493G/T) polymorphism and hepatic steatosis in hepatitis C.
METHODS
The database "Pubmed, Cochrane library, CNKI, Web of science, Embase and CBM" were retrieved to identify the literature. The quality of the selected literature was evaluated using the "the Newcastle-Ottawa Scale" (NOS). Relevant data was extracted and analyzed using the Stata software. Heterogeneity was expressed by "Cochran's Q and I", with I ≥ 50% or P < 0.05 indicating high heterogeneity. A random-effects model and subgroup analysis were conducted to identify the sources of heterogeneity. We also used "Funnel plots", "Egger's tests" and "Begg's tests" to evaluate biases in the literature.
RESULTS
The study found a significant and positive association between liver steatosis and the HCV genotype 3 with a dominant model of the MTTP genotype (-493G/T) (OR = 11.57, 95%CI: 4.467-29.962, P < 0.001). In contrast, no correlation was found between hepatic steatosis and either the recessive, homozygous or heterozygous models (OR = 1.142, P = 0.5; OR = 1.581, P = 0.081; OR = 1.029, P = 0.86). There was no significant publication biases, as measured by the Funnel plot, and the Egger's and Begg's tests. Finally, sensitivity analysis showed the obtained results are stable.
CONCLUSIONS
Dominant mutations in the T allele of the MTTP genotype (-493G/T) increase susceptibility to hepatic steatosis in patients presenting with the HCV genotype 3.
Topics: Humans; Carrier Proteins; Fatty Liver; Genotype; Hepacivirus; Hepatitis C
PubMed: 37726765
DOI: 10.1186/s12944-023-01916-x -
Frontiers in Pharmacology 2022Potassium ion (K) channels are pore-forming transmembrane proteins that control the transport of K ions. Medicinal plants are widely used as complementary therapies for... (Review)
Review
Potassium ion (K) channels are pore-forming transmembrane proteins that control the transport of K ions. Medicinal plants are widely used as complementary therapies for several disorders. Studies have shown that the modulation of K channels is most likely involved in various pharmacological effects of medicinal plants. This review aimed to evaluate the modulatory effects of medicinal plants and their active constituents on K channels under pathological conditions. This systematic review was prepared according to the Preferred Reporting Items for the Systematic Reviews and Meta-analyses (PRISMA) 2020 guideline. Four databases, including PubMed, Web of Science, embase, and Scopus, were searched. We identified 687 studies from these databases, from which we selected 13 studies for the review by using the Population, Intervention, Comparison, Outcomes, Study (PICOS) tool. The results of the 13 selected studies showed a modulatory effect of medicinal plants or their active constituents on ATP-sensitive potassium channels (K), and small (SK) and large (BK) conductance calcium-activated K channels in several pathological conditions such as nociception, brain ischemia, seizure, diabetes, gastric ulcer, myocardial ischemia-reperfusion, and hypertension via possible involvement of the nitric oxide/cyclic GMP pathway and protein kinase. K channels should be considered as significant therapeutic milestones in the treatment of several diseases. We believe that understanding the mechanism behind the interaction of medicinal plants with K channels can facilitate drug development for the treatment of various K channel-related disorders.
PubMed: 35273505
DOI: 10.3389/fphar.2022.831963 -
Biomolecules Aug 2022α-synuclein is a core component of Lewy bodies, one of the pathological hallmarks of Parkinson's disease. Aggregated α-synuclein can impair both synaptic functioning... (Review)
Review
α-synuclein is a core component of Lewy bodies, one of the pathological hallmarks of Parkinson's disease. Aggregated α-synuclein can impair both synaptic functioning and axonal transport. However, understanding the pathological role that α-synuclein plays at a cellular level is complicated as existing findings are multifaceted and dependent on the mutation, the species, and the quantity of the protein that is involved. This systematic review aims to stratify the research findings to develop a more comprehensive understanding of the role of aggregated α-synuclein on synaptic and axonal proteins in Parkinson's disease models. A literature search of the PubMed, Scopus, and Web of Science databases was conducted and a total of 39 studies were included for analysis. The review provides evidence for the dysregulation or redistribution of synaptic and axonal proteins due to α-synuclein toxicity. However, due to the high quantity of variables that were used in the research investigations, it was challenging to ascertain exactly what effect α-synuclein has on the expression of the proteins. A more standardized experimental approach regarding the variables that are employed in future studies is crucial so that existing literature can be consolidated. New research involving aggregated α-synuclein at the synapse and regarding axonal transport could be advantageous in guiding new treatment solutions.
Topics: Axons; Humans; Lewy Bodies; Parkinson Disease; Synapses; alpha-Synuclein
PubMed: 36139038
DOI: 10.3390/biom12091199 -
American Journal of Human Biology : the... Nov 2022Bone is a dynamic organ under continual turnover influenced by life history stage, energy dynamics, diet, climate, and disease. Bone turnover data have enormous...
OBJECTIVES
Bone is a dynamic organ under continual turnover influenced by life history stage, energy dynamics, diet, climate, and disease. Bone turnover data have enormous potential in biological anthropology for testing evolutionary and biocultural hypotheses, yet few studies have integrated these biomarkers. In the present article we systematically review the current availability, future viability, and applicability of measuring bone turnover markers (BTMs) in dried blood spot (DBS) samples obtained from finger prick whole blood.
METHODS
Our review considers clinical and public health relevance, biomarker stability in DBS, assay availability, and cost. We consider biomarkers of bone formation such as osteocalcin (bone matrix protein), PINP (N-terminal propeptide of type I collagen), and alkaline phosphatase (osteoblast enzyme), as well as biomarkers of bone resorption such as CTX (marker of collagen breakdown) and TRACP5b (tartrate-resistant acid phosphatase 5b; osteoclast enzyme).
RESULTS
Two BTMs have been validated for DBS: osteocalcin (formation) and TRACP5b (resorption). Prime candidates for future development are CTX and PINP, the formation and resorption markers used for clinical monitoring of response to osteoporosis treatment.
CONCLUSION
BTMs are a field-friendly technique for longitudinal monitoring of skeletal biology during growth, reproduction and aging, combining minimized risk to study participants with maximized ease of sample storage and transport. This combination allows new insights into the effects of energy availability, disease, and physical activity level on bone, and questions about bone gain and loss across life history and in response to environmental factors; these issues are important in human biology, paleoanthropology, bioarchaeology, and forensic anthropology.
Topics: Humans; Osteocalcin; Tartrate-Resistant Acid Phosphatase; Bone Remodeling; Biomarkers; Anthropology
PubMed: 36214251
DOI: 10.1002/ajhb.23816 -
Journal of Dairy Science Jan 2021Development of ketosis in high-producing dairy cows contributes to several animal health issues and highlights the need for a better understanding of the genetic basis... (Meta-Analysis)
Meta-Analysis
Development of ketosis in high-producing dairy cows contributes to several animal health issues and highlights the need for a better understanding of the genetic basis of metabolic diseases. To evaluate the pattern of differential gene expression in the liver of cows under negative energy balance (NEB), and under subclinical and clinical ketosis, a meta-analysis of gene expression and genome-wide association studies results was performed. An initial systematic review identified 118 articles based on the key words "cow," "liver," "negative energy balance," "ketosis," "expression," "qPCR," "microarray," "proteomic," "RNA-Seq," and "GWAS." After further screening for only peer-reviewed and pertinent articles for gene expression during NEB and clinical and subclinical ketosis (considering plasma levels of β-hydroxybutyrate), 20 articles were included in the analysis. From the systematic review, 430 significant SNPs identified by genome-wide association studies (GWAS) were assigned to genes reported in gene expression studies by considering chromosome and base pair positions in the ARS-UCD 1.2 bovine assembly. Venn diagrams were created to integrate the data obtained in the systematic review, and Gene Ontology enrichment analysis was carried out using official gene names. A QTL enrichment analysis was also performed to identify potential positional candidate loci. Twenty-four significant SNPs were located within the coordinates of differentially expressed genes located on chromosomes 2, 3, 6, 9, 11, 14, 27, and 29. Three significant metabolic pathways were associated with NEB and subclinical and clinical ketosis. In addition, 2 important genes, PPARA (peroxisome proliferator activated receptor alpha) and ACACA (acetyl-coenzyme A carboxylase α), were identified, which were differentially expressed in the 3 metabolic conditions. The PPARA gene is involved in the regulation of lipid metabolism and fatty liver disease and the ACACA gene encodes an enzyme that catalyzes the carboxylation of acetyl-coenzyme A to malonyl-coenzyme A, which is a rate-limiting step in fatty acid synthesis. Gene network analysis revealed co-expression interactions among 34 genes associated with functions involving fatty acid transport and fatty acid metabolism. For the annotated QTL, 9 QTL were identified for ketosis. The genes FN1 (fibronectin 1) and PTK2 (protein tyrosine kinase 2), which are mainly involved in cell adhesion and formation of extracellular matrix constituents, were enriched for QTL previously associated with the trait "ketosis" on chromosome 2 and for the trait "milk iron content" on chromosome 14, respectively. This integration of gene expression and GWAS data provides an additional understanding of the genetic background of NEB and subclinical and clinical ketosis in dairy cattle. Thus, it is a useful approach to identify biological mechanisms underlying these metabolic conditions in dairy cattle.
Topics: Animals; Cattle; Cattle Diseases; Energy Metabolism; Female; Gene Expression
PubMed: 33189279
DOI: 10.3168/jds.2020-18883 -
Disease Markers 2020As an important component of miRNA processing genes, RAN gene encodes the ras-related nuclear protein, which is a unique member of the Ras superfamily of GTPases. The... (Meta-Analysis)
Meta-Analysis
As an important component of miRNA processing genes, RAN gene encodes the ras-related nuclear protein, which is a unique member of the Ras superfamily of GTPases. The mutations in RAN gene are very likely to play a critical role in pathology-related changes to miRNA transport and expression and thus participate in tumor genesis and development. Currently, accumulating studies have explored the association between RAN SNPs and cancer risk. However, the results are conflicting. In the present study, we performed a systematic review for the association of RAN SNPs with overall cancer risk. Meanwhile, a meta-analysis was conducted based on available data, aiming at clarifying the association between RAN SNPs and cancer susceptibility. After literature search and data extraction, 17 studies containing four RAN SNPs were involved in the systematic review. And 12 studies with two highly studied SNPs (RAN rs14035 C>T and rs3803012 A>G) were included in the final meta-analysis, consisting of 7662 cases and 9807 controls. The results showed that the rs14035 polymorphism was linked to a decreased cancer risk in overall subjects and hospital-based (HB) subgroup, while the rs3803012 polymorphism conferred to an increased cancer risk in overall subjects and population-based (PB) subgroup. Our findings suggested that the two SNPs had the potential to be predictive biomarkers for cancer risk. The study would provide novel clues for the identification of miRNA-related genetic biomarkers applied to predicting cancer susceptibility.
Topics: Humans; Neoplasms; Polymorphism, Single Nucleotide; ran GTP-Binding Protein
PubMed: 32015773
DOI: 10.1155/2020/9026707 -
Urologic Oncology May 2022Determining meta-analysis of transcriptional profiling of muscle-invasive bladder cancer (MIBC) through Gene Expression Omnibus (GEO) datasets has not been investigated.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Determining meta-analysis of transcriptional profiling of muscle-invasive bladder cancer (MIBC) through Gene Expression Omnibus (GEO) datasets has not been investigated. This study aims to define gene expression profiles in MIBC and to identify potential candidate genes and pathways.
OBJECTIVES
To review and evaluate gene expression studies in MIBC through publicly available RNA sequencing (RNA-Seq) and microarray data in order to identify potential prognostic and therapeutic targets for MIBC.
METHODS
A systematic literature search of the Ovid MEDLINE, PubMed, and Wiley Cochrane Central Register of Controlled Trials databases was performed using the terms "gene," "gene expression," and "bladder cancer" January 1, 1990 through March 2021 focused on populations with MIBC.
RESULTS
In the final analysis, GEO datasets were included. Fixed effect model was employed in the meta-analysis. Gene networking connections and gene-set functional analyses of the identified genes as differentially expressed in MIBC were performed using ImaGEO and GeneMANIA software. A heatmap for the upregulated and downregulated genes was generated along with the correlated pathways.
CONCLUSION
A total of 9 genes were reported in this analysis. Six genes were reported as upregulated (ProTα, SPINT1, UBE2E1, RAB25, KPNB1, HDAC1) and 3 genes as downregulated (NUP188, IPO13, NUP124). Genes were found to be involved in "ubiquitin mediated proteolysis," "protein processing in endoplasmic reticulum," "transcriptional misregulation in cancer," and "RNA transport" pathways.
Topics: Female; Gene Expression Profiling; Gene Regulatory Networks; Humans; Male; Muscles; Neoplasm Invasiveness; Prognosis; Urinary Bladder Neoplasms; rab GTP-Binding Proteins
PubMed: 35039218
DOI: 10.1016/j.urolonc.2021.11.003