-
Gene Dec 2023Identification of genetic risk factors for PCOS susceptibility. (Meta-Analysis)
Meta-Analysis Review
IMPORTANCE
Identification of genetic risk factors for PCOS susceptibility.
OBJECTIVE
To identify genetic risk variants of the genes involved in metabolic or inflammatory pathways.
DATA SOURCES
Relevant literature was identified and extracted from PubMed, Central Cochrane Library, Google Scholar, and Science Direct by using a set of keywords related to pre-determined genes up to 06 May 2023. Study selection and synthesis: PRISMA guidelines were followed to design the protocol which is registered in PROSPERO (CRD42023422501). Pooled odds ratio (OR) and 95% confidence interval (95% CI) for different gene variants were calculated under different genetic models (dominant model, recessive model, additive model, and allele model) by using Review Manager software 4.2.
MAIN OUTCOMES
Metabolic genetic variants FTO rs9939609, IL-6 rs1800795 and CAPN10 rs3842570, rs2975760, and RAB5B rs705702 are associated with PCOS risk.
RESULTS
Forty-four relevant articles have been identified for genes involved in metabolic (n = 23) or inflammatory pathways (n = 21). There is a significant association (p < 0.05) of IL-6 rs1800795 and FTO rs9939609 with increased risk.CAPN10 rs2975760 Ins allele is suggested as a protective factor among only the non-Asian population. Also, a significant association of CAPN10 rs2975760 and RAB5B rs705702 with increased risk among the Asian population is suggested. However, no significant association could be found between CAPN10 rs3792267, rs5030952, and SUMO1P1 rs2272046, and the risk of PCOS in any of the subpopulations analysed. In silico analysis suggests the deleterious effect of IL-6 rs1800795.
CONCLUSION
and relevance: The study suggests the role of various genetic variants for genetic predisposition to PCOS among different subpopulations.
Topics: Female; Humans; Alpha-Ketoglutarate-Dependent Dioxygenase FTO; Genetic Predisposition to Disease; Interleukin-6; Polycystic Ovary Syndrome; Polymorphism, Single Nucleotide; Risk Factors
PubMed: 37714276
DOI: 10.1016/j.gene.2023.147796 -
Molecular Biotechnology Jul 2024The methylotrophic yeast Pichia pastoris is garnering interest as a chassis cell factory for the manufacture of recombinant proteins because it effectively satisfies the... (Review)
Review
The methylotrophic yeast Pichia pastoris is garnering interest as a chassis cell factory for the manufacture of recombinant proteins because it effectively satisfies the requirements of both laboratory and industrial set up. The optimisation of P. pastoris cultivation is still necessary due to strain- and product-specific problems such as promoter strength, methanol utilisation type, and culturing conditions to realize the high yields of heterologous protein(s) of interest. Techniques integrating genetic and process engineering have been used to overcome these problems. Insight into the Pichia as an expression system utilizing MUT pathway and the development of methanol free systems are highlighted in this systematic review. Recent developments in the improved production of proteins in P. pastoris by (i) diverse genetic engineering such as codon optimization and gene dosage; (ii) cultivating tactics including co-expression of chaperones; (iii) advances in the use of the 2A peptide system, and (iv) CRISPR/Cas technologies are widely discussed. We believe that by combining these strategies, P. pastoris will become a formidable platform for the production of high value therapeutic proteins.
Topics: Recombinant Proteins; Saccharomycetales; Biological Products; CRISPR-Cas Systems; Genetic Engineering; Pichia
PubMed: 37400712
DOI: 10.1007/s12033-023-00803-1 -
PloS One 2023Diabetic kidney disease (DKD) is a health burden of rising importance. Slowing progression to end stage kidney disease is the main goal of drug treatment. The aim of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Diabetic kidney disease (DKD) is a health burden of rising importance. Slowing progression to end stage kidney disease is the main goal of drug treatment. The aim of this analysis is to compare drug treatments of DKD by means of a systemic review and a network meta-analysis.
METHODS
We searched Medline, CENTRAL and clinicaltrials.gov for randomized, controlled studies including adults with DKD treated with the following drugs of interest: single angiotensin-converting-enzyme-inhibitor or angiotensin-receptor-blocker (single ACEi/ARB), angiotensin-converting-enzyme-inhibitor and angiotensin-receptor-blocker combination (ACEi+ARB combination), aldosterone antagonists, direct renin inhibitors, non-steroidal mineralocorticoid-receptor-antagonists (nsMRA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i). As primary endpoints, we defined: overall mortality and end-stage kidney disease, as secondary endpoints: renal composite outcome and albuminuria and as safety endpoints: acute kidney injury, hyperkalemia and hypotension. Under the use of a random effects model, we computed the overall effect estimates using the statistic program R4.1 and the corresponding package "netmeta". Risk of bias was assessed using the RoB 2 tool and the quality of evidence of each pairwise comparison was rated according to GRADE (Grading of Recommendations Assessment, Development and Evaluation).
RESULTS
Of initial 3489 publications, 38 clinical trials were found eligible, in total including 42346 patients. Concerning the primary endpoints overall mortality and end stage kidney disease, SGLT2i on top of single ACEi/ARB compared to single ACEi/ARB was the only intervention significantly reducing the odds of mortality (OR 0.81, 95%CI 0.70-0.95) and end-stage kidney disease (OR 0.69, 95%CI 0.54-0.88). The indirect comparison of nsMRA vs SGLT2i in our composite endpoint suggests a superiority of SGLT2i (OR 0.60, 95%CI 0.47-0.76). Concerning safety endpoints, nsMRA and SGLT2i showed benefits compared to the others.
CONCLUSIONS
As the only drug class, SGLT2i showed in our analysis beneficial effects on top of ACEi/ARB treatment regarding mortality and end stage kidney disease and by that reconfirmed its position as treatment option for diabetic kidney disease. nsMRA reduced the odds for a combined renal endpoint and did not raise any safety concerns, justifying its application.
Topics: Adult; Humans; Angiotensin-Converting Enzyme Inhibitors; Diabetic Nephropathies; Angiotensin Receptor Antagonists; Network Meta-Analysis; Sodium-Glucose Transporter 2 Inhibitors; Kidney Failure, Chronic; Angiotensins; Diabetes Mellitus
PubMed: 37917640
DOI: 10.1371/journal.pone.0293183 -
Phytomedicine : International Journal... Nov 2023Verbascoside is a natural and water-soluble phenylethanoid glycoside found in several medicinal plants. It has extensive pharmacological effects, including antioxidative... (Review)
Review
BACKGROUND
Verbascoside is a natural and water-soluble phenylethanoid glycoside found in several medicinal plants. It has extensive pharmacological effects, including antioxidative and antineoplastic actions, and a wide range of therapeutic effects against depression.
PURPOSE
In this review, we appraised preclinical and limited clinical evidence to fully discuss the anti-depression capacity of verbascoside and its holistic characteristics that can contribute to better management of depression in vivo and in vitro models, as well as, its toxicities and medicinal value.
METHODS
This review was prepared according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A systematic review of 32 preclinical trials published up to April 2023, combined with a comprehensive bioinformatics analysis of network pharmacology and molecular docking, was conducted to elucidate the antidepressant mechanism of action of verbascoside. Studies included in the systematic review were obtained from 7 electronic databases: PubMed, Scopus, Web of Science, Cochrane, ResearchGate, ScienceDirect, and Google Scholar.
RESULTS
Studies on the antidepressant effects of verbascoside showed that various pharmacological mechanisms and pathways, such as modulating the levels of monoamine neurotransmitters, inhibiting hypothalamic-pituitary-adrenal (HPA) axis hyperfunction and promoting neuroprotection may be involved in the process of its action against depression. Verbascoside promotes dopamine (DA) biosynthesis by promoting the expression of tyrosine hydroxylase mRNA and protein, upregulates the expression of 5-hydroxytryptamine receptor 1B (5-HT1B), prominence protein, microtubule-associated protein 2 (MAP2), hemeoxygenase-1 (HO-1), SQSTM1, Recombinant Autophagy Related Protein 5 (ATG5) and Beclin-1, and decreases the expression of caspase-3 and a-synuclein, thus exerting antidepressant effects. We identified seven targets (CCL2, FOS, GABARAPL1, CA9, TYR, CA12, and SQSTM1) and three signaling pathways (glutathione metabolism, metabolism of xenobiotics by cytochrome P450, fluid shear stress and atherosclerosis) as potential molecular biological sites for verbascoside.
CONCLUSIONS
These findings provide strong evidence that verbascoside exerts its antidepressant effects through various pharmacological mechanisms. However, further multicentre clinical case-control and molecularly targeted fishing studies are required to confirm the clinical efficacy of verbascoside and its underlying direct targets.
Topics: Glycosides; Molecular Docking Simulation; Neuroprotection; Sequestosome-1 Protein
PubMed: 37657207
DOI: 10.1016/j.phymed.2023.155027 -
Journal of the European Academy of... Jun 2024Rosacea is a chronic and psychologically ladened disease affecting 1%-3% of people worldwide. The identification and validation of biomarkers in rosacea patients has the... (Review)
Review
Rosacea is a chronic and psychologically ladened disease affecting 1%-3% of people worldwide. The identification and validation of biomarkers in rosacea patients has the potential to improve disease progression, support diagnosis, provide objective measures for clinical trials and aid in management. The objective of this review is to systematically identify all rosacea biomarkers, categorize them by type and identify trends to improve disease expression. Eligibility criteria for this review (PROSPERO CRD42023397510) include randomized controlled trials, case-control studies, cohort studies and other observational studies. No restrictions were placed on patient demographics (age, sex, ethnicity) or language of publication until February 2023. Quality of studies was assessed using the National Institute of Health quality assessment tool. The literature search was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. A total of 805 unique articles were screened based on the applied inclusion and exclusion criteria. After the articles were screened based on title/abstract and full-text, a total of 38 studies were included, reporting on a total of 119 unique biomarkers. The results of this review and current rosacea pathogenic mechanisms provide the greatest support for the innate cathelicidin and inflammasome, T1 and T17 pathways. The most commonly reported biomarkers include IL-1β, TNF-α, IL-37, IFN-γ and MMP-9. Biomarkers identified in this study support current theories of rosacea pathogenesis and provide direction for research to further our knowledge. However, more research is needed to identify biomarkers panels that can provide diagnostic utility. This may be difficult due to the heterogeneity of the disease and potential differences between rosacea subtypes.
Topics: Rosacea; Humans; Biomarkers; Cathelicidins; Antimicrobial Cationic Peptides
PubMed: 38078369
DOI: 10.1111/jdv.19732 -
Cureus Oct 2023The role of vitamin D in maintaining gum well-being is crucial. However, scientific research reported that the connotations of cholecalciferol and periodontal health... (Review)
Review
The role of vitamin D in maintaining gum well-being is crucial. However, scientific research reported that the connotations of cholecalciferol and periodontal health have been divested in the present literature. However, there is enormous heterogeneity in the data available. The current review aims to systematically review and appraise the available literature investigating the role of vitamin D in maintaining periodontal health. Studies included randomized controlled trials and clinical trials following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and cohort studies reporting associations between vitamin D and oral health in systemically healthy patients. Databases such as PubMed, Google Scholar, Scopus, Embase, and other sources, including hand search, were searched until May 2023 using together-equipped search sequences. Altogether, scientific articles that conform to the inclusion principles underwent a thorough eminence evaluation. All papers meeting inclusion criteria were subject to quality assessment, and the method used to assess the risk of bias was the Cochrane risk of bias tool. The search identified 1883 papers, among which 1435 were excluded after title evaluation. After abstract and title screening, 455 were excluded, and six full texts were assessed. After full-text evaluation, two articles were excluded, and only four were included. The data shows vitamin D's association with oral health maintenance. Along with its action on bone metabolism, it has extended function, which provides for its action as an anti-inflammatory agent and production of anti-microbial peptides, which help maintain oral health. Although the literature available is immense, there is enormous heterogenicity in the papers conducted to appraise the association between vitamin D and oral health. This systematic review has filtered all the data to review a few essential aspects of the role of vitamin D in maintaining oral physiology. Vitamin D has a linear relationship with periodontal health; however, the evidence is insufficient, and further studies must be done.
PubMed: 37899906
DOI: 10.7759/cureus.47773 -
Autoimmunity Reviews Sep 2023Psoriatic arthritis (PsA) is an inflammatory complex condition. Posttranslational modifications influence almost all aspects of normal cell biology and pathogenesis. The... (Review)
Review
BACKGROUND AND AIMS
Psoriatic arthritis (PsA) is an inflammatory complex condition. Posttranslational modifications influence almost all aspects of normal cell biology and pathogenesis. The aim of this systematic review was to collect all published evidence regarding posttranslational modifications in PsA, and the main outcome was to evaluate an association between disease outcomes and specific posttranslational modifications in PsA.
METHODS
A systematic electronic search was performed in Medline, PubMed, Cochrane, Virtual Health Library, and Embase databases. A total of 587 articles were identified; 59 were evaluated after removing duplicates and scanning, of which 47 were included. A descriptive analysis was conducted, with results grouped according to the type of posttranslational modification evaluated. The protocol was registered at the PROSPERO database.
RESULTS
Seven posttranslational modifications were identified: citrullination, carbamylation, phosphorylation, glycosylation, acetylation, methylation, and oxidative stress. Anti-citrullinated peptide and anti-carbamylated protein have been evaluated in rheumatoid arthritis. There is now information suggesting that these antibodies may be helpful in improving the diagnosis of PsA and that they may demonstrate a correlation with worse disease progression (erosions, polyarticular involvement, and poor treatment response). Glycosylation was associated with increased inflammation and phosphorylation products related to the expression of SIRT2 and pSTAT3 or the presence of Th17 and cytokine interleukin-22, suggesting a possible therapeutic target.
CONCLUSIONS
Posttranslational modifications often play a key role in modulating protein function in PsA and correlate with disease outcomes. Citrullination, carbamylation, phosphorylation, glycosylation, acetylation, methylation, and oxidative stress were identified as associated with diagnosis and prognosis.
Topics: Humans; Arthritis, Psoriatic; Protein Processing, Post-Translational; Citrullination; Glycosylation; Arthritis, Rheumatoid
PubMed: 37487969
DOI: 10.1016/j.autrev.2023.103393 -
JAMA Pediatrics Dec 2023Although benefits have been reported for most exercise modalities, the most effective exercise approaches for reducing insulin resistance in children and adolescents... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Although benefits have been reported for most exercise modalities, the most effective exercise approaches for reducing insulin resistance in children and adolescents with excess weight and the optimal exercise dose remain unknown.
OBJECTIVE
To compare exercise training modalities and their association with changes in insulin resistance markers among children and adolescents with excess weight and to establish the optimal exercise dose.
DATA SOURCES
For this systematic review and network meta-analysis, 6 electronic databases (PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Scopus, Web of Science, and CINAHL) were searched for studies from inception to April 1, 2023.
STUDY SELECTION
Randomized clinical trials (ie, randomized controlled trials and randomized trials without a control group) were included if they reported outcomes associated with aerobic training, resistance training, high-intensity interval training (HIIT), or a combination of these interventions.
DATA EXTRACTION AND SYNTHESIS
Data extraction for this systematic review was conducted following a network meta-analysis extension of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guideline. Effect sizes were calculated as the mean difference (MD) with 95% CI using random-effects inverse-variance models with the Hartung-Knapp-Sidik-Jonkman method. The hierarchy of competing interventions was defined using the surface under the cumulative ranking curve. The Cochrane Risk-of-Bias tool, version 2 (RoB2), was used to independently assess the risk of bias of the included studies. The certainty of evidence in consistent networks was assessed using the Grading of Recommendation, Assessment, Development and Evaluation approach. The study protocol was prospectively registered with PROSPERO. Data analyses were conducted between May and June 2023.
MAIN OUTCOMES AND MEASURES
The primary outcomes were fasting glucose, insulin, and homeostatic model assessment for insulin resistance (HOMA-IR).
RESULTS
This analysis included 55 studies with a total of 3051 children and adolescents (mean [SD] age, 13.5 [2.3] years; 1537 girls [50.4%] and 1514 boys [49.6%]). Exercise was associated with reductions in fasting insulin (MD, -4.38 μU/mL [95% CI, -5.94 to -2.82 μU/mL]) and HOMA-IR (MD, -0.87 [95% CI, -1.20 to -0.53]). A nonlinear association in both markers was observed, with a required minimal exercise dosage of approximately 900 to 1200 metabolic equivalent of task minutes per week, especially in children and adolescents with insulin resistance at baseline. Combination HIIT and resistance training and concurrent training were the most effective approaches for reducing insulin resistance markers. On average, the certainty of evidence varied from low to moderate.
CONCLUSIONS AND RELEVANCE
These findings underscore the role of exercise interventions in enhancing insulin resistance markers among children and adolescents with overweight and obesity. It is advisable to include resistance exercises alongside aerobic and HIIT programs for a minimum of two to three 60-minute sessions per week.
Topics: Male; Female; Humans; Adolescent; Child; Insulin Resistance; Network Meta-Analysis; Weight Gain; Insulin; Exercise
PubMed: 37812414
DOI: 10.1001/jamapediatrics.2023.4038 -
Wiley Interdisciplinary Reviews. RNA 2024Long noncoding RNAs (lncRNA) are a class of non-coding RNAs greater than 200 bp in length with limited peptide-coding function. The transcription of LINC00152 is... (Review)
Review
Long noncoding RNAs (lncRNA) are a class of non-coding RNAs greater than 200 bp in length with limited peptide-coding function. The transcription of LINC00152 is derived from chromosome 2p11.2. Many studies prove that LINC00152 influences the progression of various tumors via promoting the tumor cells malignant phenotype, chemoresistance, and immune escape. LINC00152 is regulated by multiple transcription factors and DNA hypomethylation. In addition, LINC00152 participates in the regulation of complex molecular signaling networks through epigenetic regulation, protein interactions, and competitive endogenous RNA (ceRNA). Here, we provide a systematic review of the upstream regulatory factors of LINC00152 expression level in different types of tumors. In addition, we revisit the main functions and mechanisms of LINC00152 as driver oncogene and biomarker in pan-cancer. This article is categorized under: RNA in Disease and Development > RNA in Disease RNA Methods > RNA Analyses in Cells RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes.
Topics: RNA, Long Noncoding; Humans; Neoplasms; Oncogenes; Gene Expression Regulation, Neoplastic
PubMed: 38702938
DOI: 10.1002/wrna.1851 -
Cells Dec 2023Atopic dermatitis (AD) is the most common chronic inflammatory skin disease and presents a major public health problem worldwide. It is characterized by a recurrent... (Review)
Review
Atopic dermatitis (AD) is the most common chronic inflammatory skin disease and presents a major public health problem worldwide. It is characterized by a recurrent and/or chronic course of inflammatory skin lesions with intense pruritus. Its pathophysiologic features include barrier dysfunction, aberrant immune cell infiltration, and alterations in the microbiome that are associated with genetic and environmental factors. There is a complex crosstalk between these components, which is primarily mediated by cytokines. Epidermal barrier dysfunction is the hallmark of AD and is caused by the disruption of proteins and lipids responsible for establishing the skin barrier. To better define the role of cytokines in stratum corneum lipid abnormalities related to AD, we conducted a systematic review of biomedical literature in PubMed from its inception to 5 September 2023. Consistent with the dominant T2 skewness seen in AD, type 2 cytokines were featured prominently as possessing a central role in epidermal lipid alterations in AD skin. The cytokines associated with T1 and T17 were also identified to affect barrier lipids. Considering the broad cytokine dysregulation observed in AD pathophysiology, understanding the role of each of these in lipid abnormalities and barrier dysfunction will help in developing therapeutics to best achieve barrier homeostasis in AD patients.
Topics: Humans; Dermatitis, Atopic; Cytokines; Epidermis; Skin; Lipids
PubMed: 38132113
DOI: 10.3390/cells12242793