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Reproductive Biomedicine Online Sep 2019This systematic review evaluated whether single nucleotide polymorphisms of AMH and AMHRII genes are associated with ovarian function. A literature search of PubMed and... (Meta-Analysis)
Meta-Analysis
This systematic review evaluated whether single nucleotide polymorphisms of AMH and AMHRII genes are associated with ovarian function. A literature search of PubMed and Embase was complemented by hand searches in the reference lists. Eight studies involving 3155 participants were included in a meta-analysis and 10 studies included for description. For AMH c.146T>G polymorphism, no significant difference in serum anti-Müllerian hormone (AMH) levels was found between participants with different genotypes (weighted mean difference [WMD] 0.42, 95% confidence interval [CI] -0.16 to 0.99). Subgroup analyses showed similar results for the European region and in healthy and infertile populations. Regarding AMHRII -482 A>G, there was no significant difference in serum AMH levels between participants with A/A genotype and G/A or G/G genotype carriers (WMD -0.04, 95% CI -0.31 to 0.23). In subgroup analysis, an interesting trend was confirmed in healthy women and polycystic ovary syndrome (PCOS) patients (WMD -0.36, 95% CI -0.63 to -0.09, P = 0.009; WMD 0.46, 95% CI 0.15 to 0.77, P = 0.004). The review suggests that AMH c.146T>G is not associated with AMH levels, while AMHRII -482 A>G may be related to AMH levels in PCOS and healthy subgroups. However, the impact of polymorphisms in the AMH signalling pathway on ovarian function still requires further investigation.
Topics: Anti-Mullerian Hormone; Female; Humans; Menopause; Ovarian Reserve; Ovulation Induction; Polymorphism, Single Nucleotide; Primary Ovarian Insufficiency; Receptors, Peptide; Receptors, Transforming Growth Factor beta; Signal Transduction
PubMed: 31253588
DOI: 10.1016/j.rbmo.2019.04.010 -
Prostate Cancer and Prostatic Diseases Mar 2020Obesity has been proposed as a risk factor for prostate cancer (PCa). In obesity, serum levels of the appetite-regulating hormones-leptin, adiponectin, and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Obesity has been proposed as a risk factor for prostate cancer (PCa). In obesity, serum levels of the appetite-regulating hormones-leptin, adiponectin, and ghrelin-become deregulated.
OBJECTIVE
To explore whether serum levels of appetite-regulating hormones associate with the incidence of PCa, the incidence of advanced disease, or PCa-specific mortality.
METHODS
PRISMA guidelines were followed. A systematic search for relevant articles published until March 2019 was performed using the databases PubMed, EMBASE, and Web of Science. Observational studies with data on serum levels of leptin, adiponectin, or ghrelin and PCa outcome were included. Meta-analysis was used to combine risk estimates. Meta-relative risks (mRRs) were calculated using random effects models. When available, raw data was pooled. Publication bias was assessed by funnel plot and Begg's test.
RESULTS
Thirty-five studies were eligible for inclusion. The qualitative analysis indicated that leptin was not consistently associated with any PCa outcome, although several cohorts reported decreased adiponectin levels in men who later developed advanced PCa. Based on the meta-analysis, there was no significant effect of leptin on PCa incidence (mRR = 0.93 (95% CI 0.75-1.16), p = 0.52) or advanced PCa (mRR = 0.90 (95% CI 0.74-1.10), p = 0.30). There were insufficient studies to estimate the mRR of PCa incidence for men with the highest levels of adiponectin. The combined risk of advanced PCa for men with the highest levels of adiponectin was reduced but did not reach significance (mRR = 0.81 (95% CI 0.61-1.08), p = 0.15).
CONCLUSIONS
The current evidence does not suggest an association between leptin and PCa outcome. However, there may be an inverse association between adiponectin and the incidence of advanced PCa that should be investigated by further studies. Serum ghrelin has not been largely investigated.
Topics: Adiponectin; Appetite; Disease Susceptibility; Epithelial Cells; Gene Expression Regulation; Ghrelin; Humans; Leptin; Male; Obesity; Peptide Hormones; Prostatic Neoplasms; Publication Bias; Signal Transduction
PubMed: 31147627
DOI: 10.1038/s41391-019-0154-1 -
Brain Injury 2019Glucagon-like peptide 1 (GLP-1) is a target for treatment of diabetes; however, its function in the brain is not well studied. In this systematic review, we aimed to...
Glucagon-like peptide 1 (GLP-1) is a target for treatment of diabetes; however, its function in the brain is not well studied. In this systematic review, we aimed to analyze the neuroprotective role of GLP-1 and its defined mechanisms. : We searched 'Web of Science' and 'Pubmed' to identify relevant studies using GLP-1 as the keyword. Two hundred and eighty-nine clinical and preclinical studies have been included. Data have been presented by grouping neurodegenerative, neurovascular and specific cell culture models. : Recent literature shows that GLP-1 and its agonists, DPP-4 inhibitors and combined GLP-1/GIP molecules are effective in partially or fully reversing the effects of neurotoxic compounds, neurovascular complications of diabetes, neuropathological changes related with Alzheimer's disease, Parkinson's disease or vascular occlusion. Possible mechanisms that provide neuroprotection are enhancing the viability of the neurons and restoring neurite outgrowth by increased neurotrophic factors, increasing subventricular zone progenitor cells, decreasing apoptosis, decreasing the level of pro-inflammatory factors, and strengthening blood-brain barrier. : Based on the preclinical studies, GLP-1 modifying agents are promising targets for neuroprotection. On the other hand, the number of clinical studies that investigate GLP-1 as a treatment is low and further clinical trials are needed for a benchside to bedside translation of recent findings.
Topics: Clinical Trials as Topic; Glucagon-Like Peptide 1; Humans; Neurodegenerative Diseases; Neuroprotection; Neuroprotective Agents; Signal Transduction
PubMed: 30938196
DOI: 10.1080/02699052.2019.1587000 -
Current Diabetes Reviews 2018With cardiovascular disease accounting for approximately 50% of deaths in patients diagnosed with type 2 diabetes, it is pertinent to initiate anti-diabetic medications... (Review)
Review
BACKGROUND
With cardiovascular disease accounting for approximately 50% of deaths in patients diagnosed with type 2 diabetes, it is pertinent to initiate anti-diabetic medications with cardiovascular benefits. This systematic clinical review critically examines the clinical therapeutic effect of lixisenatide.
METHODS
Data were gathered from articles indexed in PubMed, Google Scholar and Medline from 2010 - 2017, with the following search terms, "lixisenatide" and "GLP-1 receptor agonist". Studies written in the English language were included.
RESULTS
Thirteen clinical studies which evaluated the efficacy of lixisenatide were analyzed. Results from these studies showed that lixisenatide is an effective monotherapy in the reduction of glycated hemoglobin (A1C), Postprandial Glucose (PPG) and Fasting Blood Glucose (FPG). As an add-on therapy to metformin or sulfonylureas and insulin, it was found to be clinically effective compared to placebo. In all reviewed trials, there were higher proportions of patients who achieved A1C < 7% or < 6.5% compared to placebo without a corresponding increase in weight. Finally, the use of lixisenatide was not associated with an increased risk of cardiovascular events. The most common adverse events in all lixisenatide groups were nausea, vomiting, and diarrhea.
CONCLUSION
Lixisenatide appears to be safe and effective therapy for the management of type 2 diabetes mellitus. It is not associated with either the risk of cardiovascular events or symptomatic hypoglycemia. Finally, lixisenatide may be best used as an adjunct therapy for patients who are inadequately controlled with other diabetic medications, or select group of patients at risk of insulin induced obesity, hypertension or heart failure.
Topics: Biomarkers; Blood Glucose; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Glucagon-Like Peptide-1 Receptor; Humans; Hypoglycemic Agents; Incretins; Peptides; Protective Factors; Risk Factors; Signal Transduction; Treatment Outcome
PubMed: 28738763
DOI: 10.2174/1573399813666170724113240 -
European Journal of Endocrinology Mar 2017To investigate the differences in bone turnover between diabetic patients and controls. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To investigate the differences in bone turnover between diabetic patients and controls.
DESIGN
A systematic review and meta-analysis.
METHODS
A literature search was conducted using the databases Medline at PubMed and EMBASE. The free text search terms 'diabetes mellitus' and 'bone turnover', 'sclerostin', 'RANKL', 'osteoprotegerin', 'tartrate-resistant acid' and 'TRAP' were used. Studies were eligible if they investigated bone turnover markers in patients with diabetes compared with controls. Data were extracted by two reviewers.
RESULTS
A total of 2881 papers were identified of which 66 studies were included. Serum levels of the bone resorption marker C-terminal cross-linked telopeptide (-0.10 ng/mL (-0.12, -0.08)) and the bone formation markers osteocalcin (-2.51 ng/mL (-3.01, -2.01)) and procollagen type 1 amino terminal propeptide (-10.80 ng/mL (-12.83, -8.77)) were all lower in patients with diabetes compared with controls. Furthermore, s-tartrate-resistant acid phosphatase was decreased in patients with type 2 diabetes (-0.31 U/L (-0.56, -0.05)) compared with controls. S-sclerostin was significantly higher in patients with type 2 diabetes (14.92 pmol/L (3.12, 26.72)) and patients with type 1 diabetes (3.24 pmol/L (1.52, 4.96)) compared with controls. Also, s-osteoprotegerin was increased among patients with diabetes compared with controls (2.67 pmol/L (0.21, 5.14)).
CONCLUSIONS
Markers of both bone formation and bone resorption are decreased in patients with diabetes. This suggests that diabetes mellitus is a state of low bone turnover, which in turn may lead to more fragile bone. Altered levels of sclerostin and osteoprotegerin may be responsible for this.
Topics: Adaptor Proteins, Signal Transducing; Biomarkers; Bone Morphogenetic Proteins; Bone Remodeling; Case-Control Studies; Collagen Type II; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Genetic Markers; Humans; Osteocalcin; Osteoprotegerin; Peptide Fragments; Procollagen; Tartrate-Resistant Acid Phosphatase
PubMed: 28049653
DOI: 10.1530/EJE-16-0652 -
Biological Psychology Jan 2018Ghrelin, which is mainly released from the stomach, is the most important orexigenic regulator of food intake, inducing appetite, enhancing adiposity and releasing... (Review)
Review
Ghrelin, which is mainly released from the stomach, is the most important orexigenic regulator of food intake, inducing appetite, enhancing adiposity and releasing growth hormone. Besides the hypothalamus, ghrelin receptors (GHS-R1A) are also expressed in the mesolimbic dopaminergic system, which increases the possibility that ghrelin plays an important role in reward regulation for substance use disorders such as alcohol addiction, especially through activating the cholinergic-dopaminergic reward link. In this review we focus on the impact of ghrelin on the development and maintenance of alcohol addiction/dependence, alcohol consumption, alcohol craving and alcohol withdrawal, attempting to integrate preclinical and clinical studies concerning the intriguing relationship between appetite regulation, reward and alcohol addiction. Integrating the existing preclinical and clinical data on ghrelin antagonism, specifically at the GHS-R1A receptor in mesolimbic dopaminergic pathways, may reveal a new and innovative target for the treatment of alcohol dependence in the future.
Topics: Alcohol Drinking; Alcoholism; Animals; Appetite; Behavior, Addictive; Brain; Craving; Eating; Ghrelin; Humans; Receptors, Ghrelin; Reward; Signal Transduction; Substance Withdrawal Syndrome
PubMed: 28011402
DOI: 10.1016/j.biopsycho.2016.12.012 -
Medical Oncology (Northwood, London,... Aug 2016C-Jun activation domain-binding protein-1 (Jab1) not only is full but also a subunit (CSN5) of the constitutive photomorphogenesis 9 signalosome (CSN), which is an... (Review)
Review
C-Jun activation domain-binding protein-1 (Jab1) not only is full but also a subunit (CSN5) of the constitutive photomorphogenesis 9 signalosome (CSN), which is an evolutionarily conserved and multifunctional protein that involves in controlling cellular proliferation and apoptosis, affecting a series of pathways, as well as regulating genomic instability and DNA damage and repair. The CSN is a highly conservative protein from yeast to human and interacts with the cullin-RING family of ubiquitin ligases so that it could be execute a process of removing NEDD8, a ubiquitin-like polypeptide (deneddylase activity). The role of Jab1/CSN5's multi-function has been proved as being oncogenic in nature, what is more, Jab1/CSN5 has been confirmed by much evidence that it participates in the carcinogenesis progression and is tightly associated with poor prognosis. However, the biologic implication of Jab1/CSN5 activity during the cancer's development is unclear. We performed a systematic literature review and assessment from PubMed and Medline databases in this article. Jab1/CSN5 is participate in a lot of biologic responses, including cell proliferation, apoptosis, cell cycle regulation, DNA metabolism, invasion, DNA damage and repair, and recurrence. It also promotes cell transformation and tumorigenesis. In this review, we mainly expound the progress in the function and research advances of Jab1/CSN5 and in untangling the Jab1/CSN5 signaling pathway. Based on these bases, its potential as a therapeutic target for cancer can play a greater role in future cancer treatment.
Topics: Animals; COP9 Signalosome Complex; Carcinogenesis; Humans; Intracellular Signaling Peptides and Proteins; Neoplasms; Peptide Hydrolases; Signal Transduction
PubMed: 27412572
DOI: 10.1007/s12032-016-0805-1