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Frontiers in Endocrinology 2021To comprehensively evaluate and compare the therapeutic effects of various hypoglycemic agents in NAFLD patients with or without diabetes. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To comprehensively evaluate and compare the therapeutic effects of various hypoglycemic agents in NAFLD patients with or without diabetes.
METHODS
All literature from the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, and Clinical Trials was searched, and the language was limited to English. Two reviewers independently assessed study eligibility, continuous data extraction, and independent assessment of bias risk. Our primary outcomes were alanine aminotransferase (ALT), aspartate aminotransferase (AST) and triglyceride levels, while our secondary outcomes were high-density lipoprotein (HDL) and low-density lipoprotein (LDL) levels, body weight, BMI, and fasting glucose and glycosylated hemoglobin (HbA1c) levels.
RESULTS
The review identified 20 eligible trials that met the inclusion criteria. We found that, compared to other drugs, thiazolidinediones, especially pioglitazone, had a greater effect on the levels of ALT (-8.01 (95% CI -14.3 to 2.02)) and AST (-5.0 (95% CI -9.21 to -1,22)) and other biological indicators, but they were also associated with an increased risk of weight gain (3.62 (95% CI 2.25 to 4.99) and increased BMI (0.59 (95% Cl -0.13 to 1.29). GLP1 RAs and metformin also had better therapeutic effects than other drugs as measured by the levels of ALT (liraglutide: -9.36 (95% Cl -18 to -0.34), metformin: -2.84 (95% CI -11.09 to 5.28)) and AST (liraglutide: -5.14 (95% CI -10.69 to 0.37), metformin: -2.39 (95% CI -7.55, 2.49)) and other biological indicators.
CONCLUSION
Despite the significant risk of weight gain, thiazolidinediones, especially pioglitazone, are beneficial in normalizing liver and glucose metabolism in NAFLD patients. In clinical practice, we believe that GLP1 RAs such as liraglutide and exenatide or metformin can be used in combination to offset the risk of weight gain associated with thiazolidinediones. However, long-term studies are still needed to verify the efficacy and safety of individual hypoglycemic agents.
SYSTEMATIC REVIEW REGISTRATION
[PROSPERO], identifier [CRD42020212025].
Topics: Alanine Transaminase; Aspartate Aminotransferases; Bayes Theorem; Blood Glucose; Body Mass Index; Body Weight; Clinical Trials as Topic; Diabetes Complications; Diabetes Mellitus; Glycated Hemoglobin; Glycosylation; Humans; Hypoglycemic Agents; Lipoproteins, HDL; Lipoproteins, LDL; Metformin; Network Meta-Analysis; Non-alcoholic Fatty Liver Disease; Pioglitazone; Reproducibility of Results; Risk; Treatment Outcome
PubMed: 33841337
DOI: 10.3389/fendo.2021.649018 -
Bone Research Aug 2022Approximately 40% of treatments of chronic and recurrent osteomyelitis fail in part due to bacterial persistence. Staphylococcus aureus, the predominant pathogen in... (Review)
Review
Approximately 40% of treatments of chronic and recurrent osteomyelitis fail in part due to bacterial persistence. Staphylococcus aureus, the predominant pathogen in human osteomyelitis, is known to persist by phenotypic adaptation as small-colony variants (SCVs) and by formation of intracellular reservoirs, including those in major bone cell types, reducing susceptibility to antibiotics. Intracellular infections with S. aureus are difficult to treat; however, there are no evidence-based clinical guidelines addressing these infections in osteomyelitis. We conducted a systematic review of the literature to determine the demonstrated efficacy of all antibiotics against intracellular S. aureus relevant to osteomyelitis, including protein biosynthesis inhibitors (lincosamides, streptogramins, macrolides, oxazolidines, tetracyclines, fusidic acid, and aminoglycosides), enzyme inhibitors (fluoroquinolones and ansamycines), and cell wall inhibitors (beta-lactam inhibitors, glycopeptides, fosfomycin, and lipopeptides). The PubMed and Embase databases were screened for articles related to intracellular S. aureus infections that compared the effectiveness of multiple antibiotics or a single antibiotic together with another treatment, which resulted in 34 full-text articles fitting the inclusion criteria. The combined findings of these studies were largely inconclusive, most likely due to the plethora of methodologies utilized. Therefore, the reported findings in the context of the models employed and possible solutions for improved understanding are explored here. While rifampicin, oritavancin, linezolid, moxifloxacin and oxacillin were identified as the most effective potential intracellular treatments, the scientific evidence for these is still relatively weak. We advocate for more standardized research on determining the intracellular effectiveness of antibiotics in S. aureus osteomyelitis to improve treatments and patient outcomes.
PubMed: 35961964
DOI: 10.1038/s41413-022-00227-8 -
Neurological Sciences : Official... Dec 2019CYP19A1 enzyme (aromatase) encoded by CYP19A1 (cytochrome p450 family 19 subfamily a member 1) gene plays a key role in the biosynthesis of estrogen, which has been... (Meta-Analysis)
Meta-Analysis
Association between rs10046, rs1143704, rs767199, rs727479, rs1065778, rs1062033, rs1008805, and rs700519 polymorphisms in aromatase (CYP19A1) gene and Alzheimer's disease risk: a systematic review and meta-analysis involving 11,051 subjects.
BACKGROUND
CYP19A1 enzyme (aromatase) encoded by CYP19A1 (cytochrome p450 family 19 subfamily a member 1) gene plays a key role in the biosynthesis of estrogen, which has been significantly associated with Alzheimer's disease (AD). To ascertain whether CYP19A1 gene polymorphisms are correlated with the susceptibility to AD, we performed this systematic review and meta-analysis of currently available studies.
MATERIALS AND METHODS
A comprehensive literature search was conducted by using PubMed, Embase, and Web of Science databases and the Cochrane Library. The association was evaluated by using odds ratios (ORs) and 95% confidence intervals (CIs) through Stata software (version 12.0).
RESULTS
A total of eight articles including 39 case-control studies with 11,051 subjects including 3215 AD cases and 7836 controls were involved in this meta-analysis. By pooling all eligible studies, we detected that rs10046, rs1143704, rs767199, and rs727479 polymorphisms in CYP19A1 gene were significantly associated with AD risk. A significant association between rs10046 polymorphism and AD risk was found under allele contrast, homozygous (TT vs CC: OR = 1.17, 95%CI = 1.02-1.34, I = 0.0%, P = 0.026), and dominant genetic models. In addition, we observed an association between with rs1143704 polymorphism under heterozygous and dominant genetic models (TT+TA vs AA: OR = 1.36, 95%CI = 1.03-1.79, I = 0.0%, P = 0.033). Similar results were found in rs767199 and rs727479 polymorphisms, while null results were found for other polymorphisms.
CONCLUSIONS
This systematic review and meta-analysis suggested that the rs10046, rs1143704, rs767199, and rs727479 polymorphisms in CYP19A1 gene significantly increase AD susceptibility. In addition, our results demonstrated that homozygous TT genotype in rs10046, dominant AA and AG genotypes in rs767199, homozygous TT genotype in rs727479, and dominant TT and TA genotypes in rs1143704 might be the susceptibility genotypes for AD, while no associations were observed between rs1065778, rs1062033, rs1008805, and rs700519 polymorphisms and AD susceptibility.
Topics: Alzheimer Disease; Aromatase; Genetic Predisposition to Disease; Humans
PubMed: 31278540
DOI: 10.1007/s10072-019-04003-1 -
American Journal of Medical Genetics.... Jul 2020Variations in SLC9A9 gene expression and protein function are associated with multiple human diseases, which range from Attention-deficit/hyperactivity disorder (ADHD)...
Variations in SLC9A9 gene expression and protein function are associated with multiple human diseases, which range from Attention-deficit/hyperactivity disorder (ADHD) to glioblastoma multiforme. In an effort to determine the full spectrum of human disease associations with SLC9A9, we performed a systematic review of the literature. We also review SLC9A9's biochemistry, protein structure, and function, as well as its interacting partners with the goal of identifying mechanisms of disease and druggable targets. We report gaps in the literature regarding the genes function along with consistent trends in disease associations that can be used to further research into treating the respective diseases. We report that SLC9A9 has strong associations with neuropsychiatric diseases and various cancers. Interestingly, we find strong overlap in SLC9A9 disease associations and propose a novel role for SLC9A9 in neuropsychiatric comorbidity. In conclusion, SLC9A9 is a multifunctional protein that, through both its endosome regulatory function and its protein-protein interaction network, has the ability to modulate signaling axes, such as the PI3K pathway, among others.
Topics: Alternative Splicing; Attention Deficit Disorder with Hyperactivity; Autism Spectrum Disorder; Autophagy; Comorbidity; Exons; Genetic Predisposition to Disease; HEK293 Cells; Humans; Mental Disorders; Phosphatidylinositol 3-Kinases; Protein Interaction Mapping; Protein Processing, Post-Translational; Signal Transduction; Sodium-Hydrogen Exchangers
PubMed: 32400953
DOI: 10.1002/ajmg.b.32787 -
Medicine Nov 2019The kinesin family (KIF) is reported to be aberrantly expressed and significantly correlated with survival outcomes in patients with various cancers. This meta-analysis... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The kinesin family (KIF) is reported to be aberrantly expressed and significantly correlated with survival outcomes in patients with various cancers. This meta-analysis was carried out to quantitatively evaluate the prognostic values of partial KIF members in cancer patients.
METHODS
Two well-known KIF members, KIF2A and KIF20A, were investigated to evaluate their potential values as novel prognostic biomarkers in human cancer. A comprehensive literature search was carried out of the PubMed, EMBASE, Cochrane Library, and Web of Science databases up to April 2019. Pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the association of KIF2A and KIF20A expression with overall survival (OS) and clinicopathological parameters.
RESULTS
Twenty-five studies involving 7262 patients were finally incorporated, including nine about KIF2A and sixteen about KIF20A. Our results indicated that patients with high expression of KIF2 and KIF20A tended to have shorter OS than those with low expression (HR = 2.23, 95% CI = 1.87-2.65, P < .001; HR = 1.77, 95% CI = 1.57-1.99, P < .001, respectively). Moreover, high expression of these 2 KIF members was significantly associated with advanced clinical stage (OR = 1.98, 95% CI: 1.57-2.50, P < .001; OR = 2.63, 95% CI: 2.03-3.41, P < .001, respectively), positive lymph node metastasis (OR = 2.32, 95% CI: 1.65-3.27, P < .001; OR = 2.13, 95% CI: 1.59-2.83, P < .001, respectively), and distant metastasis (OR = 2.20, 95% CI: 1.21-3.99, P = .010; OR = 5.25, 95% CI: 2.82-9.77, P < .001, respectively); only high KIF20A expression was related to poor differentiation grade (OR = 1.82, 95% CI: 1.09-3.07, P = .023).
CONCLUSIONS
High expression of KIF2 and KIF20A in human cancer was significantly correlated with worse prognosis and unfavorable clinicopathological features, suggesting that these 2 KIF members can be used as prognostic biomarkers for different types of tumors.
PROSPERO REGISTRATION NUMBER
CRD42019134928.
Topics: Biomarkers, Tumor; Humans; Kinesins; Lymphatic Metastasis; Neoplasms; Prognosis; Proportional Hazards Models
PubMed: 31725680
DOI: 10.1097/MD.0000000000018040 -
Annual Review of Biochemistry Jun 2021Codon usage bias, the preference for certain synonymous codons, is found in all genomes. Although synonymous mutations were previously thought to be silent, a large body...
Codon usage bias, the preference for certain synonymous codons, is found in all genomes. Although synonymous mutations were previously thought to be silent, a large body of evidence has demonstrated that codon usage can play major roles in determining gene expression levels and protein structures. Codon usage influences translation elongation speed and regulates translation efficiency and accuracy. Adaptation of codon usage to tRNA expression determines the proteome landscape. In addition, codon usage biases result in nonuniform ribosome decoding rates on mRNAs, which in turn influence the cotranslational protein folding process that is critical for protein function in diverse biological processes. Conserved genome-wide correlations have also been found between codon usage and protein structures. Furthermore, codon usage is a major determinant of mRNA levels through translation-dependent effects on mRNA decay and translation-independent effects on transcriptional and posttranscriptional processes. Here, we discuss the multifaceted roles and mechanisms of codon usage in different gene regulatory processes.
Topics: Animals; Codon Usage; Eukaryota; Gene Expression; Humans; Protein Biosynthesis; Protein Folding; RNA, Messenger; RNA, Transfer; Ribosomes
PubMed: 33441035
DOI: 10.1146/annurev-biochem-071320-112701 -
Oral Oncology Jul 2020The presence of Programmed Death-Ligand 1 protein (PD-L1) in oral squamous cell carcinoma (OSCC) may indicate an ability to evade immune response and has been suggested... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The presence of Programmed Death-Ligand 1 protein (PD-L1) in oral squamous cell carcinoma (OSCC) may indicate an ability to evade immune response and has been suggested as a prognostic marker, but there is controversy in the literature.
OBJECTIVE
To review the scientific evidence of a prognostic role for PD-L1 levels in OSCC.
METHODS
PubMed, Embase, Web of Science, and Scopus were searched for studies published on or before March 02, 2019. Studies measuring PD-L1 levels by immunohistochemistry (IHC) in OSCC were included. Study quality was assessed using the QUIPS tool. Meta-analysis was performed for survival outcomes and clinic-pathological parameters.
RESULTS
26 articles were included comprising 2532 patients. Analysis of studies measuring PD-L1 expression in the cell membrane showed a worse prognosis for disease-specific survival (HR = 1.74, 95% CI = 1.14-2.66, p = 0.01) and disease-free survival (HR = 1.56, 95% CI = 1.16-2.09, p = 0.003). PD-L1 overexpression was more likely in females (OR = 0.69, 95% CI = 0.53-0.91, p = 0.008), non-smokers (OR = 0.45, 95% CI = 0.27-0.75, p = 0.002), non-drinkers (OR = 0.40, 95% CI = 0.16-0.97, p = 0.04), advance stage tumours (OR = 1.63, 95% CI = 1.00-2.64, p = 0.05) and in tumours with high levels of PD-1 (OR = 33.36, 95% CI = 1.88-591.69, p = 0.02), CD4+ (OR = 3.25, 95% CI = 1.36-7.76, p = 0.008) and CD8+ (OR = 3.63 , 95% CI = 1.20-10.99, p = 0.02).
CONCLUSION
This meta-analysis found a worse prognosis in OSCCs overexpressing PD-L1 in the cell membrane as measured by disease specific survival and disease-free survival. We also found positive correlations between PD-L1 overexpression and advanced tumours, females, non-smokers, non-drinkers and high levels of tumour PD-1, CD4, and CD8.
Topics: B7-H1 Antigen; Disease-Free Survival; Female; Humans; Male; Mouth Neoplasms; Prognosis; Squamous Cell Carcinoma of Head and Neck; Survival Rate
PubMed: 32330687
DOI: 10.1016/j.oraloncology.2020.104722 -
Experimental Physiology Jun 2024Bed rest and limb immobilization are models of muscle disuse associated with skeletal muscle atrophy and reduced strength. The purpose of this systematic review was to... (Meta-Analysis)
Meta-Analysis
Bed rest and limb immobilization are models of muscle disuse associated with skeletal muscle atrophy and reduced strength. The purpose of this systematic review was to examine the impact of protein or amino acid provision before and/or during a period of muscle disuse on muscle atrophy (primary outcome), strength and muscle protein synthesis (secondary outcomes) following a disuse period. We performed a systematic review of Embase, MEDLINE, Web of Science, PubMed and Clinical Trials in December 2022. Eligible studies were randomized controlled trials that combined a dietary protein or amino acid intervention versus control during an experimental model of disuse (bed rest or unilateral limb immobilization) in healthy individuals aged ≥18 years. Nine articles from eight independent trials were identified and rated for risk of bias by two authors. A meta-analysis of muscle mass data revealed no effect (standardized mean difference: 0.2; 95% confidence interval: -0.18 to 0.57, P = 0.31) of protein/amino acid intervention in preventing disuse-induced muscle atrophy. Although the meta-analysis was not conducted on strength or muscle protein synthesis data, there was insufficient evidence in the reviewed articles to support the use of protein/amino acid provision in mitigating the disuse-induced decline in either outcome measurement. Additional high-quality studies, including the reporting of randomization procedures and blinding procedures and the provision of statistical analysis plans, might be required to determine whether protein or amino acid provision serves as an effective strategy to attenuate muscle atrophy during periods of disuse.
Topics: Adult; Humans; Amino Acids; Bed Rest; Dietary Proteins; Immobilization; Muscle Proteins; Muscle Strength; Muscle, Skeletal; Muscular Atrophy
PubMed: 38424716
DOI: 10.1113/EP090434 -
Molecular Neurobiology Jan 2023Despite annual increases in the incidence and prevalence of neurodegenerative diseases, there is a lack of effective treatment strategies. An increasing number of E3... (Review)
Review
Despite annual increases in the incidence and prevalence of neurodegenerative diseases, there is a lack of effective treatment strategies. An increasing number of E3 ubiquitin ligases (E3s) and deubiquitinating enzymes (DUBs) have been observed to participate in the pathogenesis mechanisms of neurodegenerative diseases, on the basis of which we conducted a systematic literature review of the studies. This review will help to explore promising therapeutic targets from highly dynamic ubiquitination modification processes.
Topics: Humans; Ubiquitin-Protein Ligases; Neurodegenerative Diseases; Ubiquitination
PubMed: 36260224
DOI: 10.1007/s12035-022-03063-3 -
Journal of Neurochemistry Mar 2021The liver-derived, circulating transport protein transthyretin (TTR) is the cause of systemic hereditary (ATTRv) and wild-type (ATTRwt) amyloidosis. TTR stabilization...
The liver-derived, circulating transport protein transthyretin (TTR) is the cause of systemic hereditary (ATTRv) and wild-type (ATTRwt) amyloidosis. TTR stabilization and knockdown are approved therapies to mitigate the otherwise lethal disease course. To date, the variety in phenotypic penetrance is not fully understood. This systematic review summarizes the current literature on TTR pathophysiology with its therapeutic implications. Tetramer dissociation is the rate-limiting step of amyloidogenesis. Besides destabilizing TTR mutations, other genetic (RBP4, APCS, AR, ATX2, C1q, C3) and external (extracellular matrix, Schwann cell interaction) factors influence the type of onset and organ tropism. The approved small molecule tafamidis stabilizes the tetramer and significantly decelerates the clinical course. By sequence-specific mRNA knockdown, the approved small interfering RNA (siRNA) patisiran and antisense oligonucleotide (ASO) inotersen both significantly reduce plasma TTR levels and improve neuropathy and quality of life compared to placebo. With enhanced hepatic targeting capabilities, GalNac-conjugated siRNA and ASOs have recently entered phase III clinical trials. Bivalent TTR stabilizers occupy both binding groves in vitro, but have not been tested in trials so far. Tolcapone is another stabilizer with the potential to cross the blood-brain barrier, but its half-life is short and liver failure a potential side effect. Amyloid-directed antibodies and substances like doxycycline aim at reducing the amyloid load, however, none of the yet developed antibodies has successfully passed clinical trials. ATTR-amyloidosis has become a model disease for pathophysiology-based treatment. Further understanding of disease mechanisms will help to overcome the remaining limitations, including application burden, side effects, and blood-brain barrier permeability.
Topics: Amyloid; Amyloidosis, Familial; Animals; Gene Knockdown Techniques; Humans; Prealbumin
PubMed: 33155274
DOI: 10.1111/jnc.15233