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Human Reproduction (Oxford, England) Jun 2023What is the influence of body composition during childhood, adolescence, and adulthood, as well as metabolic parameters, on incident polycystic ovary syndrome (PCOS)? (Meta-Analysis)
Meta-Analysis
STUDY QUESTION
What is the influence of body composition during childhood, adolescence, and adulthood, as well as metabolic parameters, on incident polycystic ovary syndrome (PCOS)?
SUMMARY ANSWER
Excess body fat, even during childhood/adolescence, and metabolic parameters, suggestive of hyperinsulinaemia/insulin resistance, significantly impact the risk of PCOS in a linear fashion.
WHAT IS KNOWN ALREADY
Observational and Mendelian randomization (MR) data have demonstrated an association between adulthood overweight/obesity and development of PCOS. However, the contribution of body composition in childhood/adolescence to incident PCOS is unclear, as is the influence of childhood overweight/obesity.
STUDY DESIGN, SIZE, DURATION
We conducted a systematic review and meta-analysis and integrated our results with a previously published systematic review. Two blinded investigators screened abstracts published between November 2010 and May 2021. Furthermore, we incorporated summary statistics from genome-wide association study (GWAS) data in subjects of European ancestry. Adult overweight was defined as BMI ≥ 25 kg/m2 and obesity as BMI ≥ 30 kg/m2; in Asian subjects, overweight was defined as BMI ≥ 23 kg/m2 and obesity as BMI ≥ 25 kg/m2.
PARTICIPANTS/MATERIALS, SETTING, METHODS
We utilized meta-analysis and MR together to allow synthesis of genetic and observational data. For the systematic review, the search revealed 71 studies, of which 63 were included in meta-analysis by calculating odds ratios (ORs) using the random-effects model. Furthermore, we conducted a two-sample MR study of GWAS data to determine the impact of childhood and adult body size (defined categorically by BMI and childhood body size proportions), abnormal body composition and metabolic parameters (higher fasting serum insulin or lower sex hormone-binding globulin (SHBG) concentration) on the odds of incident PCOS via the inverse-variance weighted method.
MAIN RESULTS AND THE ROLE OF CHANCE
Significant associations were shown between body composition and PCOS incidence. From the systematic review/meta-analysis, women with overweight (OR 3.80, 2.87-5.03), obesity (OR 4.99, 3.74-6.67), and central obesity (OR 2.93, 2.08-4.12) had increased odds of PCOS. For adolescents with overweight and/or obesity, the PCOS odds were greater than for adults. From MR, for every standard deviation increase in BMI (4.8 kg/m2), the odds of PCOS increased by 2.76 (2.27-3.35). Childhood body size had an independent effect on PCOS odds after adjusting for adult body size (OR: 2.56, 1.57-4.20). Genetically determined body fat percentage (OR 3.05, 2.24-4.15), whole body fat mass (OR 2.53, 2.04-3.14), fasting serum insulin (OR 6.98, 2.02-24.13), and SHBG concentration (OR 0.74, 0.64-0.87) were all significantly associated with PCOS in a linear relation.
LIMITATIONS, REASONS FOR CAUTION
The meta-analysis included studies which were cross-sectional and retrospective, limiting our ability to determine causality. MR was limited by interrogating subjects only of European ancestry and including cases classified by either self-diagnosis or diagnostic criteria.
WIDER IMPLICATIONS OF THE FINDINGS
Our study demonstrates for the first time a critical role of the impact of excess childhood/adolescent adiposity on the pathophysiology of adult PCOS. Our results, driven by genetically determined childhood/adolescent body composition, higher BMI, hyperinsulinaemia, and lower SHBG, clearly favour obesity driving the metabolic, but not reproductive, PCOS phenotype. Overall, effective weight maintenance, even from the early years, is likely to reduce the risk of this reproductive endocrine disorder.
STUDY FUNDING/COMPETING INTEREST(S)
S.S.Z. was funded by a National Institute for Health and Care Research (NIHR) Academic Clinical Lectureship. U.A. is chair of the NIHR Steering Committee Trial-CASSANDRA-DN. No other authors declare any sources of funding or relevant conflicts of interest. The authors declare that the research was conducted in the absence of any commercial or financial relations that could be construed as a potential conflict of interest.
TRIAL REGISTRATION NUMBER
N/A.
Topics: Humans; Female; Polycystic Ovary Syndrome; Overweight; Adiposity; Retrospective Studies; Genome-Wide Association Study; Mendelian Randomization Analysis; Body Mass Index; Obesity; Insulin Resistance; Insulins
PubMed: 37015099
DOI: 10.1093/humrep/dead053 -
Clinica Chimica Acta; International... Jun 2022The potential of disease-modifying therapies for Alzheimer's disease has greatly stimulated interest in the development of minimally invasive testing for early... (Review)
Review
BACKGROUND AND AIMS
The potential of disease-modifying therapies for Alzheimer's disease has greatly stimulated interest in the development of minimally invasive testing for early identification of at-risk individuals. Accordingly, identification of blood-based biomarkers is paramount. The recent discovery of plasma phosphorylated at threonine217 (p-tau217) may provide a turning point in Alzheimer's disease detection. This systematic review aims to evaluate the available evidence on the use of plasma p-tau217 as a marker to predict Alzheimer's disease and to monitor disease progression.
MATERIAL AND METHODS
This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Study quality was assessed using the QUADAS-2 tool. In total, 676 publications were identified, of which 16 were in accordance with the pre-defined eligibility criteria.
RESULTS
Current evidence shows that plasma p-tau217 is a sensitive maker of the clinical manifestation and progression of Alzheimer's disease and of pathological changes associated with this condition, including amyloid accumulation, tau burden, brain atrophy and physical degradation. Moreover, given that plasma p-tau217 does not predict such changes in patients with other neurodegenerative disorders, plasma p-tau217 is also specific to Alzheimer's disease.
CONCLUSION
More large, diverse community studies are needed to harmonize plasma p-tau217 measurements and to determine widely applicable diagnostic cut-off values.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Biomarkers; Disease Progression; Humans; tau Proteins
PubMed: 35341762
DOI: 10.1016/j.cca.2022.03.018 -
Proteomics Mar 2023Peptide-mediated interactions (PMIs) play a crucial role in cell signaling network, which are responsible for about half of cellular protein-protein associations in the... (Review)
Review
Peptide-mediated interactions (PMIs) play a crucial role in cell signaling network, which are responsible for about half of cellular protein-protein associations in the human interactome and have recently been recognized as a new kind of promising druggable target for drug development and disease therapy. In this article, we give a systematic review regarding the proteome-wide discovery of PMIs and targeting druggable PMIs (dPMIs) with chemical drugs, self-inhibitory peptides (SIPs) and protein agents, particularly focusing on their implications and applications for therapeutic purpose in omics. We also introduce computational peptidology strategies used to model, analyze, and design PMI-targeted molecular entities and further extend the concepts of protein context, direct/indirect readout, and enthalpy/entropy effect involved in PMIs. Current issues and future perspective on this topic are discussed. There is still a long way to go before establishment of efficient therapeutic strategies to target PMIs on the omics scale.
Topics: Humans; Peptides; Proteins; Entropy
PubMed: 36461811
DOI: 10.1002/pmic.202200175 -
Obesity Reviews : An Official Journal... Aug 2023Glucagon-like peptide 1 (GLP-1) analogs regulate body weight and liver steatosis. Different body adipose tissue (AT) depots exhibit biological variability. Accordingly,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Glucagon-like peptide 1 (GLP-1) analogs regulate body weight and liver steatosis. Different body adipose tissue (AT) depots exhibit biological variability. Accordingly, GLP-1 analog effects on AT distribution are unclear.
OBJECTIVES
To investigate GLP1-analog effects on adiposity distribution.
SEARCH METHODS
PubMed, Cochrane, and Scopus databases were screened for eligible randomized human trials. Pre-defined endpoints included visceral AT (VAT), subcutaneous AT (SAT), total AT (TAT), epicardial AT (EAT), liver AT (LAT), and waist-to-hip ratio (W:H). Search was conducted until May 17, 2022.
DATA COLLECTION AND ANALYSIS
Data extraction and bias assessment were performed by two independent investigators. Treatment effects were estimated using random effects models. Analyses were performed on Review Manager v5.3.
MAIN RESULTS
Out of the 367 screened studies, 45 were included in the systematic review and 35 were used in the meta-analysis. GLP-1 analogs reduced VAT, SAT, TAT, LAT, and EAT, with non-significant effects on W:H. Overall bias risk was low.
CONCLUSIONS
GLP-1 analog treatment reduces TAT, affecting most studied AT depots, including the pathogenic VAT, EAT, and LAT. GLP-1 analogs may have significant roles in combating metabolic, obesity-associated diseases via reductions of key AT depot volumes.
Topics: Humans; Adiposity; Glucagon-Like Peptide 1; Obesity; Body Weight; Liver
PubMed: 37191219
DOI: 10.1111/obr.13574 -
Journal of Cosmetic Dermatology Jun 2019Glutathione is one of agents which is commonly used to lighten skin color in Asia as a dietary supplement. Previous studies suggest its potential effect of glutathione...
BACKGROUND
Glutathione is one of agents which is commonly used to lighten skin color in Asia as a dietary supplement. Previous studies suggest its potential effect of glutathione on skin color. However, the clinical efficacy of glutathione in oral form is still questionable due to its limited absorption and bioavailability.
AIM
To determine the clinical effects of glutathione on skin color and related skin conditions.
PATIENTS/METHODS
A systematic review was conducted using PubMed, CINAHL, Scopus, EMBASE and Cochrane library were searched from inceptions to October 2017. All clinical studies evaluating the effect of glutathione on any skin effects in healthy volunteer were included.
RESULTS
A total of four studies were included. Three studies were RCTs with placebo control, while one was a single-arm trial. One study used topical form, while others used oral form of glutathione with 250 to 500 mg/day. We found that both oral glutathione with the dosage of 500 mg/day and topical 2.0% oxidized glutathione could brighten skin color in sun-exposed area measured by skin melanin index. No significant differences in the reduction in skin melanin index were observed in sun-protected area for any products. In addition, glutathione also has a trend to improve skin wrinkle, skin elasticity, and UV spots. Some adverse events but nonserious were reported.
CONCLUSIONS
Current evidence of the skin whitening effect of glutathione is still inconclusive due to the quality of included studies and inconsistent findings. However, there is a trend that glutathione might brighten skin color at skin-exposed area.
Topics: Administration, Cutaneous; Administration, Oral; Biological Availability; Dietary Supplements; Glutathione; Humans; Melanins; Randomized Controlled Trials as Topic; Skin; Skin Absorption; Skin Lightening Preparations; Skin Pigmentation; Sunlight; Treatment Outcome
PubMed: 30895708
DOI: 10.1111/jocd.12910 -
International Journal of Molecular... Nov 2022Fibroblast growth factor 21 is a pleiotropic hormone secreted mainly by the liver in response to metabolic and nutritional challenges. Physiologically, fibroblast growth... (Review)
Review
Fibroblast growth factor 21 is a pleiotropic hormone secreted mainly by the liver in response to metabolic and nutritional challenges. Physiologically, fibroblast growth factor 21 plays a key role in mediating the metabolic responses to fasting or starvation and acts as an important regulator of energy homeostasis, glucose and lipid metabolism, and insulin sensitivity, in part by its direct action on the central nervous system. Accordingly, pharmacological recombinant fibroblast growth factor 21 therapies have been shown to counteract obesity and its related metabolic disorders in both rodents and nonhuman primates. In this systematic review, we discuss how fibroblast growth factor 21 regulates metabolism and its interactions with the central nervous system. In addition, we also state our vision for possible therapeutic uses of this hepatic-brain axis.
Topics: Animals; Fibroblast Growth Factors; Liver; Insulin Resistance; Brain; Energy Metabolism
PubMed: 36362103
DOI: 10.3390/ijms232113318 -
Molecular Neurodegeneration Nov 2022The family of VPS10p-Domain (D) receptors comprises five members named SorLA, Sortilin, SorCS1, SorCS2 and SorCS3. While their physiological roles remain incompletely... (Review)
Review
The family of VPS10p-Domain (D) receptors comprises five members named SorLA, Sortilin, SorCS1, SorCS2 and SorCS3. While their physiological roles remain incompletely resolved, they have been recognized for their signaling engagements and trafficking abilities, navigating a number of molecules between endosome, Golgi compartments, and the cell surface. Strikingly, recent studies connected all the VPS10p-D receptors to Alzheimer's disease (AD) development. In addition, they have been also associated with diseases comorbid with AD such as diabetes mellitus and major depressive disorder. This systematic review elaborates on genetic, functional, and mechanistic insights into how dysfunction in VPS10p-D receptors may contribute to AD etiology, AD onset diversity, and AD comorbidities. Starting with their functions in controlling cellular trafficking of amyloid precursor protein and the metabolism of the amyloid beta peptide, we present and exemplify how these receptors, despite being structurally similar, regulate various and distinct cellular events involved in AD. This includes a plethora of signaling crosstalks that impact on neuronal survival, neuronal wiring, neuronal polarity, and synaptic plasticity. Signaling activities of the VPS10p-D receptors are especially linked, but not limited to, the regulation of neuronal fitness and apoptosis via their physical interaction with pro- and mature neurotrophins and their receptors. By compiling the functional versatility of VPS10p-D receptors and their interactions with AD-related pathways, we aim to further propel the AD research towards VPS10p-D receptor family, knowledge that may lead to new diagnostic markers and therapeutic strategies for AD patients.
Topics: Humans; Alzheimer Disease; Amyloid beta-Peptides; Depressive Disorder, Major; Protein Transport; Nerve Growth Factors
PubMed: 36397124
DOI: 10.1186/s13024-022-00576-2 -
Journal of Affective Disorders Apr 2023Growing evidence suggests that epigenetic modification is vital in biological processes of depression. Findings from studies exploring the associations between DNA... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Growing evidence suggests that epigenetic modification is vital in biological processes of depression. Findings from studies exploring the associations between DNA methylation and depression have been inconsistent.
METHODS
A systematical search of EMBASE, PubMed, Web of Science, and PsycINFO databases was conducted to include studies focusing on the associations between DNA methylation and depression (up to November 1st 2021) according to PRISMA guidelines with registration in PROSPERO (CRD42021288664).
RESULTS
A total of 47 studies met inclusion criteria and 31 studies were included in the meta-analysis. This meta-analysis found that genes hypermethylation, including BDNF (OR: 1.15, 95%CI: 1.01-1.32, I = 90 %), and NR3C1 (OR: 1.43, 95%CI: 1.09-1.87, I = 88 %) was associated with increased risk of depression. Significant association of SLC6A4 hypermethylation with depression was only found in the subgroup of using original data (OR: 1.09, 95%CI: 1.01-1.19, I = 52 %). BDNF hypermethylation could increase the risk of depression only in the Asian population (OR: 1.18, 95%CI: 1.01-1.40, I = 91 %), and significant associations of NR3C1 hypermethylation with depression were found in the group for depressive symptoms (OR: 1.34, 95%CI: 1.08-1.67, I = 85 %), but not for depressive disorder (OR: 1.89, 95%CI: 0.54-6.55, I = 94 %).
LIMITATIONS
More studies are needed to explore the factors that might influence the estimates owing to the contextual heterogeneity of the pooling of included studies.
CONCLUSIONS
It is noted that DNA hypermethylation, namely BDNF and NR3C1, is associated with increased risk of depression. The findings in this study could provide some material evidence for preventing and diagnosing of depression.
Topics: Humans; Brain-Derived Neurotrophic Factor; Depression; DNA Methylation; Epigenesis, Genetic; Serotonin Plasma Membrane Transport Proteins
PubMed: 36717033
DOI: 10.1016/j.jad.2023.01.079 -
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 -
Biomolecules Jul 2020The grass family (Poaceae) is one of the largest families of flowering plants, growing in all climatic zones of all continents, which includes species of exceptional... (Review)
Review
The grass family (Poaceae) is one of the largest families of flowering plants, growing in all climatic zones of all continents, which includes species of exceptional economic importance. The high adaptability of grasses to adverse environmental factors implies the existence of efficient resistance mechanisms that involve the production of antimicrobial peptides (AMPs). Of plant AMPs, defensins represent one of the largest and best-studied families. Although wheat and barley seed γ-thionins were the first defensins isolated from plants, the functional characterization of grass defensins is still in its infancy. In this review, we summarize the current knowledge of the characterized defensins from cultivated and selected wild-growing grasses. For each species, isolation of defensins or production by heterologous expression, peptide structure, biological activity, and structure-function relationship are described, along with the gene expression data. We also provide our results on in silico mining of defensin-like sequences in the genomes of all described grass species and discuss their potential functions. The data presented will form the basis for elucidation of the mode of action of grass defensins and high adaptability of grasses to environmental stress and will provide novel potent molecules for practical use in medicine and agriculture.
Topics: Defensins; Disease Resistance; Gene Expression Regulation, Plant; Models, Molecular; Plant Proteins; Poaceae; Protein Conformation; Structure-Activity Relationship
PubMed: 32664422
DOI: 10.3390/biom10071029