-
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 -
Journal of Inherited Metabolic Disease May 2020Since the first description of galactosemia in 1908 and despite decades of research, the pathophysiology is complex and not yet fully elucidated. Galactosemia is an...
Since the first description of galactosemia in 1908 and despite decades of research, the pathophysiology is complex and not yet fully elucidated. Galactosemia is an inborn error of carbohydrate metabolism caused by deficient activity of any of the galactose metabolising enzymes. The current standard of care, a galactose-restricted diet, fails to prevent long-term complications. Studies in cellular and animal models in the past decades have led to an enormous progress and advancement of knowledge. Summarising current evidence in the pathophysiology underlying hereditary galactosemia may contribute to the identification of treatment targets for alternative therapies that may successfully prevent long-term complications. A systematic review of cellular and animal studies reporting on disease complications (clinical signs and/or biochemical findings) and/or treatment targets in hereditary galactosemia was performed. PubMed/MEDLINE, EMBASE, and Web of Science were searched, 46 original articles were included. Results revealed that Gal-1-P is not the sole pathophysiological agent responsible for the phenotype observed in galactosemia. Other currently described contributing factors include accumulation of galactose metabolites, uridine diphosphate (UDP)-hexose alterations and subsequent impaired glycosylation, endoplasmic reticulum (ER) stress, altered signalling pathways, and oxidative stress. galactokinase (GALK) inhibitors, UDP-glucose pyrophosphorylase (UGP) up-regulation, uridine supplementation, ER stress reducers, antioxidants and pharmacological chaperones have been studied, showing rescue of biochemical and/or clinical symptoms in galactosemia. Promising co-adjuvant therapies include antioxidant therapy and UGP up-regulation. This systematic review provides an overview of the scattered information resulting from animal and cellular studies performed in the past decades, summarising the complex pathophysiological mechanisms underlying hereditary galactosemia and providing insights on potential treatment targets.
Topics: Animals; Disease Models, Animal; Galactokinase; Galactose; Galactosemias; Genotype; Humans; Oxidative Stress; Phenotype; UDPglucose 4-Epimerase; UTP-Hexose-1-Phosphate Uridylyltransferase
PubMed: 31808946
DOI: 10.1002/jimd.12202 -
BioMed Research International 2021Type 2 deiodinase (Dio2) is a selenoenzyme that is mainly expressed in the endoplasmic reticulum of the central nervous system, brown adipose tissue, and placenta and is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Type 2 deiodinase (Dio2) is a selenoenzyme that is mainly expressed in the endoplasmic reticulum of the central nervous system, brown adipose tissue, and placenta and is responsible for outer ring deiodination of thyroxine (T4) to form biologically active triiodothyronine (T3). The Thr92Ala polymorphism of Dio2 has been found to be a potential risk factor for various diseases beyond the hypothalamus-pituitary-thyroid (HPT) axis.
METHODS
We searched the relevant studies in the PubMed, Embase, and Cochrane Library databases and Google Scholar. A systematic review and meta-analysis of studies on the Thr92Ala polymorphism and metabolic parameters beyond the HPT axis (e.g., BMI, fasting glycemic traits, plasma lipid levels, and hypertension risk) were performed.
RESULTS
Six eligible studies that analyzed the relationship between the Thr92Ala polymorphism and metabolic parameters beyond the thyroid were identified. All selected studies excluded patients with thyroid dysfunction, and diabetic patients were also excluded when fasting glucose and fasting insulin levels were meta-analyzed. The Thr92Ala polymorphism was found to be a significant risk factor for higher BMI (Std. mean difference 0.31 (0.01, 0.60), = 0.04) and higher fasting glucose levels (Std. mean difference 1.18 (0.05, 2.31), = 0.04). However, fasting insulin levels, plasma lipid levels, and hypertension risk showed a nonsignificant association with the Thr92Ala polymorphism.
CONCLUSION
Compared with euthyroid noncarriers (Thr/Thr), euthyroid Ala92-Dio2 carriers showed increased BMI levels, and Ala92-Dio2 carriers also had higher fasting plasma glucose levels than matched euthyroid nondiabetic noncarriers.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Blood Glucose; Body Mass Index; Fasting; Female; Genetic Association Studies; Humans; Hypertension; Iodide Peroxidase; Lipids; Male; Middle Aged; Polymorphism, Single Nucleotide; Risk Factors; Young Adult
PubMed: 34660805
DOI: 10.1155/2021/9914009 -
Current Drug Targets 2019In previous studies, oxidative stress damage has been solely considered to be the mechanism of ovarian aging, and several antioxidants have been used to delay ovarian...
In previous studies, oxidative stress damage has been solely considered to be the mechanism of ovarian aging, and several antioxidants have been used to delay ovarian aging. But recently, more reports have found that endoplasmic reticulum stress, autophagy, sirtuins, mitochondrial dysfunction, telomeres, gene mutation, premature ovarian failure, and polycystic ovary syndrome are all closely related to ovarian aging, and these factors all interact with oxidative stress. These novel insights on ovarian aging are summarized in this review. Furthermore, as a pleiotropic molecule, melatonin is an important antioxidant and used as drugs for several diseases treatment. Melatonin regulates not only oxidative stress, but also the various molecules, and normal and pathological processes interact with ovarian functions and aging. Hence, the mechanism of ovarian aging and the extensive role of melatonin in the ovarian aging process are described herein. This systematic review supply new insights into ovarian aging and the use of melatonin to delay its onset, further supply a novel drug of melatonin for ovarian aging treatment.
Topics: Aging; Autophagy; Endoplasmic Reticulum Stress; Female; Humans; Melatonin; Mitochondria; Ovary; Oxidative Stress; Sirtuins
PubMed: 30156157
DOI: 10.2174/1389450119666180828144843 -
Experimental Diabetes Research 2012Diabetic nephropathy is a serious complication of diabetes mellitus, and its prevalence has been increasing worldwide. Therefore, there is an urgent need to identify a... (Review)
Review
Diabetic nephropathy is a serious complication of diabetes mellitus, and its prevalence has been increasing worldwide. Therefore, there is an urgent need to identify a new therapeutic target to prevent diabetic nephropathy. Autophagy is a major catabolic pathway involved in degrading and recycling macromolecules and damaged organelles to maintain intracellular homeostasis. The study of autophagy in mammalian systems is advancing rapidly and has revealed that it is involved in the pathogenesis of various metabolic or age-related diseases. The functional role of autophagy in the kidneys is also currently under intense investigation although, until recently, evidence showing the involvement of autophagy in the pathogenesis of diabetic nephropathy has been limited. We provide a systematic review of autophagy and discuss the therapeutic potential of autophagy in diabetic nephropathy to help future investigations in this field.
Topics: AMP-Activated Protein Kinases; Animals; Autophagy; Diabetic Nephropathies; Endoplasmic Reticulum; Homeostasis; Humans; Hypoxia; Kidney; Mice; Microscopy, Electron; Nephrons; Oxidative Stress; Prevalence; Reactive Oxygen Species; Sirtuin 1; TOR Serine-Threonine Kinases
PubMed: 22028701
DOI: 10.1155/2012/628978 -
Frontiers in Neuroscience 2022Spinal cord injury (SCI) is a devastating condition with few treatment options. Metformin, a classical antidiabetic and antioxidant, has extended its application to...
The effect of metformin on ameliorating neurological function deficits and tissue damage in rats following spinal cord injury: A systematic review and network meta-analysis.
Spinal cord injury (SCI) is a devastating condition with few treatment options. Metformin, a classical antidiabetic and antioxidant, has extended its application to experimental SCI treatment. Here, we performed a systematic review to evaluate the neurobiological roles of metformin for treating SCI in rats, and to assess the potential for clinical translation. PubMed, Embase, China National Knowledge Infrastructure, WanFang data, SinoMed, and Vip Journal Integration Platform databases were searched from their inception dates to October 2021. Two reviewers independently selected controlled studies evaluating the neurobiological roles of metformin in rats following SCI, extracted data, and assessed the quality of methodology and evidence. Pairwise meta-analyses, subgroup analyses and network analysis were performed to assess the roles of metformin in neurological function and tissue damage in SCI rats. Twelve articles were included in this systematic review. Most of them were of moderate-to-high methodological quality, while the quality of evidence from those studies was not high. Generally, Basso, Beattie, and Bresnahan scores were increased in rats treated with metformin compared with controls, and the weighted mean differences (WMDs) between metformin and control groups exhibited a gradual upward trend from the 3rd (nine studies, = 164, WMD = 0.42, 95% CI = -0.01 to 0.85, = 0.06) to the 28th day after treatment (nine studies, = 136, WMD = 3.48, 95% CI = 2.04 to 4.92, < 0.00001). Metformin intervention was associated with improved inclined plane scores, tissue preservation ratio and number of anterior horn motor neurons. Subgroup analyses indicated an association between neuroprotection and metformin dose. Network meta-analysis showed that 50 mg/kg metformin exhibited greater protection than 10 and 100 mg/kg metformin. The action mechanisms behind metformin were associated with activating adenosine monophosphate-activated protein kinase signaling, regulating mitochondrial function and relieving endoplasmic reticulum stress. Collectively, this review indicates that metformin has a protective effect on SCI with satisfactory safety and we demonstrate a rational mechanism of action; therefore, metformin is a promising candidate for future clinical trials. However, given the limitations of animal experimental methodological and evidence quality, the findings of this pre-clinical review should be interpreted with caution.
PubMed: 36117612
DOI: 10.3389/fnins.2022.946879 -
Oxidative Medicine and Cellular... 2016Cancer is a leading cause of death worldwide. We aim to provide a systematic review about the roles of reactive oxygen species (ROS) in anticancer therapy with Salvia... (Review)
Review
Cancer is a leading cause of death worldwide. We aim to provide a systematic review about the roles of reactive oxygen species (ROS) in anticancer therapy with Salvia miltiorrhiza Bunge (Danshen). Danshen, including its lipophilic and hydrophilic constituents, is potentially beneficial for treating various cancers. The mechanisms of ROS-related anticancer effects of Danshen vary depending on the specific type of cancer cells involved. Danshen may enhance TNF-α-induced apoptosis, upregulate caspase-3, caspase-8, caspase-9, endoplasmic reticulum stress, P21, P53, Bax/Bcl-2, DR5, and AMP-activated protein kinase, or activate the p38/JNK, mitogen-activated protein kinase, and FasL signaling pathways. Conversely, Danshen may downregulate human telomerase reverse transcriptase mRNA, telomerase, survivin, vascular endothelial growth factor/vascular endothelial growth factor receptor 2, CD31, NF-κB, Erk1/2, matrix metalloproteinases, microtubule assembly, and receptor tyrosine kinases including epidermal growth factor receptors, HER2, and P-glycoprotein and inhibit the PI3K/Akt/mTOR or estrogen receptor signaling pathways. Therefore, Danshen may inhibit cancer cells proliferation through antioxidation on tumor initiation and induce apoptosis or autophagy through ROS generation on tumor progression, tumor promotion, and tumor metastasis. Based on the available evidence regarding its anticancer properties, this review provides new insights for further anticancer research or clinical trials with Danshen.
Topics: Animals; Antineoplastic Agents; Drugs, Chinese Herbal; Humans; Hydrophobic and Hydrophilic Interactions; Neoplasms; Reactive Oxygen Species; Salvia miltiorrhiza
PubMed: 27579153
DOI: 10.1155/2016/5293284 -
Molecular Neurobiology Feb 2024The development of central nervous system (CNS) can form perceptual, memory, and cognitive functions, while injuries to CNS often lead to severe neurological dysfunction... (Review)
Review
The development of central nervous system (CNS) can form perceptual, memory, and cognitive functions, while injuries to CNS often lead to severe neurological dysfunction and even death. As one of the prevalent post-translational modifications (PTMs), O-GlcNAcylation has recently attracted great attentions due to its functions in regulating the activity, subcellular localization, and stability of target proteins. It has been indicated that O-GlcNAcylation could interact with phosphorylation, ubiquitination, and methylation to jointly regulate the function and activity of proteins. Furthermore, a growing number of studies have suggested that O-GlcNAcylation played an important role in the CNS. During development, O-GlcNAcylation participated in the neurogenesis, neuronal development, and neuronal function. In addition, O-GlcNAcylation was involved in the progress of CNS injuries including ischemic stroke, subarachnoid hemorrhage (SAH), and intracerebral hemorrhage (ICH) and played a crucial role in the improvement of brain damage such as attenuating cognitive impairment, inhibiting neuroinflammation, suppressing endoplasmic reticulum (ER) stress, and maintaining blood-brain barrier (BBB) integrity. Therefore, O-GlcNAcylation showed great promise as a potential target in CNS development and injuries. In this article, we presented a review highlighting the role of O-GlcNAcylation in CNS development and injuries. Hence, on the basis of these properties and effects, intervention with O-GlcNAcylation may be developed as therapeutic agents for CNS diseases.
PubMed: 38367136
DOI: 10.1007/s12035-024-04045-3 -
Addiction (Abingdon, England) Sep 2022Genomic and transcriptomic findings greatly broaden the biological knowledge regarding substance use. However, systematic convergence and comparison evidence of...
Common and distinguishing genetic factors for substance use behavior and disorder: an integrated analysis of genomic and transcriptomic studies from both human and animal studies.
BACKGROUND AND AIMS
Genomic and transcriptomic findings greatly broaden the biological knowledge regarding substance use. However, systematic convergence and comparison evidence of genome-wide findings is lacking for substance use. Here, we combined all the genome-wide findings from both substance use behavior and disorder (SUBD) and identified common and distinguishing genetic factors for different SUBDs.
METHODS
Systemic literature search for genome-wide association (GWAS) and RNA-seq studies of alcohol/nicotine/drug use behavior (partially meets or not reported diagnostic criteria) and alcohol use behavior and disorder (AUBD), nicotine use behavior and disorder (NUBD) and drug use behavior and disorder (DUBD) was performed using PubMed and the GWAS catalog. Drug use was focused upon cannabis, opioid, cocaine and methamphetamine use. GWAS studies required case-control or case/cohort samples. RNA-seq studies were based on brain tissues. The genes which contained significant single nucleotide polymorphism (P ≤ 1 × 10 ) in GWAS and reported as significant in RNA-seq studies were extracted. Pathway enrichment was performed by using Metascape. Gene interaction networks were identified by using the Protein Interaction Network Analysis database.
RESULTS
Total SUBD-related 2910 genes were extracted from 75 GWAS studies (2 773 889 participants) and 17 RNA-seq studies. By overlapping the genes and pathways of AUBD, NUBD and DUBD, four shared genes (CACNB2, GRIN2B, PLXDC2 and PKNOX2), four shared pathways [two Gene Ontology (GO) terms of 'modulation of chemical synaptic transmission', 'regulation of trans-synaptic signaling', two Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of 'dopaminergic synapse', 'cocaine addiction'] were identified (significantly higher than random, P < 1 × 10 ). The top shared KEGG pathways (Benjamini-Hochberg-corrected P-value < 0.05) in the pairwise comparison of AUBD versus DUBD, NUBD versus DUBD, AUBD versus NUBD were 'Epstein-Barr virus infection', 'protein processing in endoplasmic reticulum' and 'neuroactive ligand-receptor interaction', respectively. We also identified substance-specific genetic factors: i.e. ADH1B and ALDH2 were unique for AUBD, while CHRNA3 and CHRNA4 were unique for NUBD.
CONCLUSIONS
This systematic review identifies the shared and unique genes and pathways for alcohol, nicotine and drug use behaviors and disorders at the genome-wide level and highlights critical biological processes for the common and distinguishing vulnerability of substance use behaviors and disorders.
Topics: Aldehyde Dehydrogenase, Mitochondrial; Animals; Cocaine; Epstein-Barr Virus Infections; Genetic Predisposition to Disease; Genome-Wide Association Study; Genomics; Herpesvirus 4, Human; Humans; Nicotine; Polymorphism, Single Nucleotide; Substance-Related Disorders; Tobacco Use Disorder; Transcriptome
PubMed: 35491750
DOI: 10.1111/add.15908 -
Frontiers in Pharmacology 2024Matrine, an alkaloid derived from the dried roots of Aiton, has been utilized for the treatment of liver diseases, but its potential hepatotoxicity raises concerns....
Matrine, an alkaloid derived from the dried roots of Aiton, has been utilized for the treatment of liver diseases, but its potential hepatotoxicity raises concerns. However, the precise condition and mechanism of action of matrine on the liver remain inconclusive. Therefore, the objective of this systematic review and meta-analysis is to comprehensively evaluate both the hepatoprotective and hepatotoxic effects of matrine and provide therapeutic guidance based on the findings. The meta-analysis systematically searched relevant preclinical literature up to May 2023 from eight databases, including PubMed, Web of Science, Cochrane Library, Embase, China National Knowledge Infrastructure, WanFang Med Online, China Science and Technology Journal Database, and China Biomedical Literature Service System. The CAMARADES system assessed the quality and bias of the evidence. Statistical analysis was conducted using STATA, which included the use of 3D maps and radar charts to display the effects of matrine dosage and frequency on hepatoprotection and hepatotoxicity. After a thorough screening, 24 studies involving 657 rodents were selected for inclusion. The results demonstrate that matrine has bidirectional effects on ALT and AST levels, and it also regulates SOD, MDA, serum TG, serum TC, IL-6, TNF-α, and CAT levels. Based on our comprehensive three-dimensional analysis, the optimal bidirectional effective dosage of matrine ranges from 10 to 69.1 mg/kg. However, at a dose of 20-30 mg/kg/d for 0.02-0.86 weeks, it demonstrated high liver protection and low toxicity. The molecular docking analysis revealed the interaction between MT and SERCA as well as SREBP-SCAP complexes. Matrine could alter Ca homeostasis in liver injury via multiple pathways, including the SREBP1c/SCAP, Notch/RBP-J/HES1, IκK/NF-κB, and Cul3/Rbx1/Keap1/Nrf2. Matrine has bidirectional effects on the liver at doses ranging from 10 to 69.1 mg/kg by influencing Ca homeostasis in the cytoplasm, endoplasmic reticulum, Golgi apparatus, and mitochondria. https://inplasy.com/, identifier INPLASY202340114.
PubMed: 38348397
DOI: 10.3389/fphar.2024.1315584