-
Reproductive Biology and Endocrinology... Oct 2016Women with PCOS have elevated levels of the harmful Advanced Glycation End Products (AGEs), which are highly reactive molecules formed after glycation of lipids and... (Review)
Review
BACKGROUND
Women with PCOS have elevated levels of the harmful Advanced Glycation End Products (AGEs), which are highly reactive molecules formed after glycation of lipids and proteins. Additionally, AGEs accumulate in the ovaries of women with PCOS potentially contributing to the well-documented abnormal steroidogenesis and folliculogenesis.
MAIN BODY
A systematic review of articles and abstracts available in PubMed was conducted and presented in a systemic manner. This article reports changes in steroidogenic enzyme activity in granulosa and theca cells in PCOS and PCOS-models. It also described the changes in AGEs and their receptors in the ovaries of women with PCOS and presents the underlying mechanism(s) whereby AGEs could be responsible for the PCOS-related changes in granulosa and theca cell function thus adversely impacting steroidogenesis and follicular development. AGEs are associated with hyperandrogenism in PCOS possibly by altering the activity of various enzymes such as cholesterol side-chain cleavage enzyme cytochrome P450, steroidogenic acute regulatory protein, 17α-hydroxylase, and 3β-hydroxysteroid dehydrogenase. AGEs also affect luteinizing hormone receptor and anti-Mullerian hormone receptor expression as well as their signaling pathways in granulosa cells.
CONCLUSIONS
A better understanding of how AGEs alter granulosa and theca cell function is likely to contribute meaningfully to a conceptual framework whereby new interventions to prevent and/or treat ovarian dysfunction in PCOS can ultimately be developed.
Topics: 3-Hydroxysteroid Dehydrogenases; Animals; Cholesterol Side-Chain Cleavage Enzyme; Female; Glycation End Products, Advanced; Gonadal Steroid Hormones; Granulosa Cells; Humans; Ovary; Phosphoproteins; Polycystic Ovary Syndrome; Receptors, LH; Receptors, Peptide; Receptors, Transforming Growth Factor beta; Steroid 17-alpha-Hydroxylase; Theca Cells
PubMed: 27769286
DOI: 10.1186/s12958-016-0205-6 -
International Journal of Molecular... Dec 2022Vitamin D takes part in the functioning of many processes that ensure the homeostasis of the body. In orthopedics, it is indicated as an inseparable element ensuring... (Review)
Review
Vitamin D takes part in the functioning of many processes that ensure the homeostasis of the body. In orthopedics, it is indicated as an inseparable element ensuring proper bone growth and functioning, and its deficiencies are indicated in various diseases, mainly in the proper structure and function of the skeleton. In this review, we focus on the most important components of the vitamin D metabolic pathway, in correlation with selected orthopedic conditions. Records were obtained from the PubMed database in a timeline of 2010-2022. The keywords were as follows: vitamin D/cholesterol/vitamin D binding protein/ VDBP/Cytochrome/CYP24A1/CYP 27B1/Vitamin D receptor/VDR/ + diseases (ACL reconstruction, rotator cuff, arthroplasty knee/hip/shoulder). The recent original studies were analyzed, discussed, and the most important data were shown. The vast majority of articles concern the metabolite of vitamin D (25(OH)D), which is measured as a standard in diagnostic laboratories. Even though there is a lot of valuable information in the literature, we believe that the other elements of the vitamin D pathway also deserve attention and suggest their research in correlation with orthopedic disorders to supplement the missing knowledge on this topic.
Topics: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase; Metabolic Networks and Pathways; Orthopedics; Receptors, Calcitriol; Vitamin D; Vitamin D3 24-Hydroxylase; Vitamins
PubMed: 36555202
DOI: 10.3390/ijms232415556 -
Advances in Nutrition (Bethesda, Md.) Mar 2023PUFA status is highly implicated in cognitive development and metabolic disorder-related diseases. Genetic variants of FADS genes encoding enzymes that catalyze the... (Meta-Analysis)
Meta-Analysis Review
PUFA status is highly implicated in cognitive development and metabolic disorder-related diseases. Genetic variants of FADS genes encoding enzymes that catalyze the rate-limiting steps of PUFA biosynthesis appear to be associated with n-3 and n-6 PUFA contents. Therefore, we conducted the first systematic review and meta-analysis to explore the association of the A-allele carriers of the FADS1 rs174556 with PUFA status. The PRISMA guidelines were followed. The literature search was conducted up to November 2022 in PubMed, Web of Science, Embase, Cochrane Library, Airiti Library, and CINAHL. The Joanna Briggs Institute checklists were used to assess the methodological quality. The correlation with 95% CIs was determined by a random-effect meta-analysis. Eleven studies that met the inclusion criteria and acceptable quality were included in this systematic review. The data on PUFA contents were collected when they were mainly analyzed using blood samples and breast milk. Results of the meta-analysis on eight studies (one randomized controlled trial, one cohort study, and six cross-sectional studies) showed that the A-allele carriers of rs174556 were significantly negatively correlated with the concentrations of AA (P = 0.001), EPA (P = 0.004), and DHA (P = 0.025). However, ALA and LA were not associated with the A-allele carriers. To clarify the discrepancy, we further divided the studies into blood samples and breast milk subgroups. The subgroup analysis revealed that the A-allele carriers of rs174556 were significantly positively correlated with LA (P = 0.031) and negatively correlated with AA (P = 0.001), EPA (P = 0.036), and DHA (P < 0.001) in the blood sample group, but not in the breast milk group. The current meta-analysis proved that the A-allele carriers of the FADS1 rs174556 appeared to be highly associated with lower concentrations of AA, EPA, and DHA but higher LA in the blood samples. The study has been registered on the International Prospective Register of Systematic Reviews (PROSPERO:CRD42022363978). Adv Nutr 2023;x:xx-xx.
Topics: Female; Humans; Fatty Acid Desaturases; Cohort Studies; Cross-Sectional Studies; Polymorphism, Single Nucleotide; Fatty Acids, Unsaturated; Genotype; Randomized Controlled Trials as Topic
PubMed: 36806496
DOI: 10.1016/j.advnut.2023.01.007 -
Medicine Sep 2018Human cytochrome P450 (CYP) is an enzyme responsible for the metabolic activation of many carcinogens, including nitrosamines. CYP2E1 represents a major CYP isoform and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Human cytochrome P450 (CYP) is an enzyme responsible for the metabolic activation of many carcinogens, including nitrosamines. CYP2E1 represents a major CYP isoform and is expressed in the human urothelial cells. Recent studies have investigated the association of CYP2E1 gene polymorphisms with bladder cancer risk but have shown contradictory results. Hence, we performed a systematic literature review and meta-analysis to assess the association between CYP2E1 gene polymorphisms and bladder cancer.
METHODS
Systematic literature searches were conducted with PubMed, Excerpt Medica Database, Science Direct/Elsevier, China National Knowledge Infrastructure, and the Cochrane Library up to January 2018 for studies that involved the association of CYP2E1 gene polymorphisms with bladder cancer risk. A meta-analysis was performed with Review Manager and Stata software. Combined odds ratios (ORs) were identified with 95% confidence intervals (CIs) in a random or fixed effects model.
ETHICS
The protocol was approved by the institutional review board of each study center. Written informed consent will be obtained from all patients before registration, in accordance with the Declaration of Helsinki.
RESULTS
Eight studies were identified, including 1733 cases of bladder cancer and 1814 normal controls. Our results illustrated that there are significant associations between CYP2E1 gene polymorphisms and bladder cancer in all genetic models (P < .05). The combined ORs and 95% CIs were as follows for each model: additive model [OR 0.56; 95% CI (0.38-0.82)]; dominant model [OR 0.79; 95% CI (0.67-0.93)]; recessive model [OR 0.61; 95% CI (0.41-0.89)]; codominant model [OR 0.80; 95% CI (0.67-0.96)]; allele model [OR 0.75; 95% CI (0.59-0.95)]. A subgroup study showed that there are also significant associations between CYP2E1 gene polymorphisms and bladder cancer in Asian people. However, there are no significant associations between CYP2E1 gene polymorphisms and bladder cancer in Caucasian populations.
CONCLUSIONS
The present study provides evidence for an association between CYP2E1 gene polymorphisms and bladder cancer progression, and suggests that CYP2E1 gene polymorphisms might be a protective factor against bladder cancer in Asian people. However, studies with larger sample sizes are needed to confirm the correlation between CYP2E1 gene polymorphisms and bladder cancer.
Topics: Cytochrome P-450 CYP2E1; Disease Progression; Genetic Predisposition to Disease; Humans; Polymorphism, Genetic; Urinary Bladder; Urinary Bladder Neoplasms
PubMed: 30278485
DOI: 10.1097/MD.0000000000011910 -
Medicine Mar 2018This meta-analysis aims to examine whether the MspI and Ile462Val polymorphisms of cytochrome P450 1A1 (CYP1A1) are associated with cervical cancer risk. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This meta-analysis aims to examine whether the MspI and Ile462Val polymorphisms of cytochrome P450 1A1 (CYP1A1) are associated with cervical cancer risk.
METHODS
Eligible case-control studies were identified dated until July 2017. Pooled odds ratios (ORs) were used to assess the strength of the association between the two variants and cervical cancer risk.
RESULTS
Thirteen studies were eligible (2148 cases and 2252 controls) concerning MspI polymorphism and 8 studies were eligible (1466 cases and 1690 controls) for Ile462Val polymorphism. MspI polymorphism seemed to result in cervical cancer risk in any genetic model (C allele vs T allele: OR = 1.44, 95% confidence interval [CI] = 1.16-1.79; heterozygous model: OR = 1.40, 95% CI = 1.08-1.82; homozygous model: OR = 2.22, 95% CI = 1.48-3.33, dominant model: OR = 1.50, 95% CI = 1.14-1.98 and recessive model: OR = 1.80, 95% CI = 1.35-2.41); similar significantly increased risk was found among Caucasians and Asians. Ile462Val polymorphism was associated with elevated cervical cancer risk (Val allele vs Ile allele: OR = 1.85, 95% CI = 1.27-2.67; heterozygous model: OR = 1.42, 95% CI = 1.28-1.61; homozygous model: OR = 2.94, 95% CI = 1.15-7.54; dominant model: OR = 2.00, 95% CI = 1.33-3.00); this finding was replicated upon Caucasian population.
CONCLUSION
This meta-analysis demonstrated that polymorphisms in MspI and Ile462Val of CYP1A1 were risk factors for developing cervical cancer.
Topics: Alleles; Asian People; Cytochrome P-450 CYP1A1; Female; Genetic Predisposition to Disease; Humans; Odds Ratio; Polymorphism, Single Nucleotide; Risk Factors; Uterine Cervical Neoplasms; White People
PubMed: 29595663
DOI: 10.1097/MD.0000000000010210 -
Cells Oct 2022Major depressive disorder (MDD) and bipolar disorder (BD) with melancholia and psychotic features and suicidal behaviors are accompanied by activated immune-inflammatory... (Meta-Analysis)
Meta-Analysis Review
The Tryptophan Catabolite or Kynurenine Pathway in a Major Depressive Episode with Melancholia, Psychotic Features and Suicidal Behaviors: A Systematic Review and Meta-Analysis.
Major depressive disorder (MDD) and bipolar disorder (BD) with melancholia and psychotic features and suicidal behaviors are accompanied by activated immune-inflammatory and oxidative pathways, which may stimulate indoleamine 2,3-dioxygenase (IDO), the first and rate-limiting enzyme of the tryptophan catabolite (TRYCAT) pathway resulting in increased tryptophan degradation and elevated tryptophan catabolites (TRYCTAs). The purpose of the current study is to systematically review and meta-analyze levels of TRP, its competing amino acids (CAAs) and TRYCATs in patients with severe affective disorders. Methods: PubMed, Google Scholar and SciFinder were searched in the present study and we recruited 35 studies to examine 4647 participants including 2332 unipolar (MDD) and bipolar (BD) depressed patients and 2315 healthy controls. Severe patients showed significant lower ( < 0.0001) TRP (standardized mean difference, SMD = -0.517, 95% confidence interval, CI: -0.735; -0.299) and TRP/CAAs (SMD = -0.617, CI: -0.957; -0.277) levels with moderate effect sizes, while no significant difference in CAAs were found. Kynurenine (KYN) levels were unaltered in severe MDD/BD phenotypes, while the KYN/TRP ratio showed a significant increase only in patients with psychotic features (SMD = 0.224, CI: 0.012; 0.436). Quinolinic acid (QA) was significantly increased (SMD = 0.358, CI: 0.015; 0.701) and kynurenic acid (KA) significantly decreased (SMD = -0.260, CI: -0.487; -0.034) in severe MDD/BD. Patients with affective disorders with melancholic and psychotic features and suicidal behaviors showed normal IDO enzyme activity but a lowered availability of plasma/serum TRP to the brain, which is probably due to other processes such as low albumin levels.
Topics: Albumins; Amino Acids; Depressive Disorder, Major; Humans; Indoleamine-Pyrrole 2,3,-Dioxygenase; Kynurenic Acid; Kynurenine; Quinolinic Acids; Suicidal Ideation; Tryptophan
PubMed: 36231075
DOI: 10.3390/cells11193112 -
International Journal of Molecular... Aug 2022Studies have demonstrated the link between vitamin-D-related genetic variations and nonskeletal outcomes. We aimed to identify all available data on the association of... (Review)
Review
BACKGROUND
Studies have demonstrated the link between vitamin-D-related genetic variations and nonskeletal outcomes. We aimed to identify all available data on the association of vitamin-D-related genetic variations with nonalcoholic fatty liver disease (NAFLD).
METHODS
Potentially eligible studies were identified from Embase and Medline databases from inception to June 2022 using a search strategy that comprised terms for "Vitamin D" and "NAFLD". Eligible studies must report the association between vitamin D-related genetic variations and presence, severity or response to treatment of NAFLD. Data were extracted from each eligible study.
RESULTS
A total of 3495 articles were identified. After a systematic review, twelve studies were included. A total of 26 genetic variations were identified. Presence of NAFLD was associated with variations of (rs222054, rs222020, rs10011000, rs7041), (rs2228570, rs11168287, rs10783219, rs4752), (rs3787557, rs6068816, rs2296241, rs2248359) and (rs4646536). Severity of NAFLD was associated with variations of (rs4588), (rs2228570, rs4334089), (rs10741657), (rs1544410, rs3829251, rs12785878) and (rs3787557, rs6068816, rs6097809, rs6127119, rs2248359, rs3787554, rs4809960, rs6022999). Response to calcitriol treatment was associated with variation of (rs10735810).
CONCLUSIONS
Multiple vitamin D-related genetic variations were associated with NAFLD, indicating the role of vitamin D in the pathogenesis of NAFLD.
Topics: Cholestanetriol 26-Monooxygenase; Cytochrome P450 Family 2; Genetic Variation; Genotype; Humans; Non-alcoholic Fatty Liver Disease; Polymorphism, Single Nucleotide; Receptors, Calcitriol; Vitamin D; Vitamin D3 24-Hydroxylase; Vitamins
PubMed: 36012386
DOI: 10.3390/ijms23169122 -
Pharmacogenomics 2015Drug addiction is a serious disease with damaging effects on the brain and physical health. Despite the increase in the number of affected individuals, there are few... (Meta-Analysis)
Meta-Analysis Review
Drug addiction is a serious disease with damaging effects on the brain and physical health. Despite the increase in the number of affected individuals, there are few effective pharmacological treatment options for substance use disorders. The study of the influence of an individual's genetic features on the treatment response may help to identify more efficacious treatment options. This systematic review focuses on the serotonergic system because of its relevant role in mood and impulse control disorders, and its contribution to the development and maintenance of drug use disorders. In particular, we examine the role of serotonergic genes in the response to pharmacotherapy for alcohol, cocaine and nicotine addiction. Current evidence suggests that genetic variability of the serotonergic biosynthesis enzyme tryptophan hydroxylase 2 (TPH2) and the serotonin transporter (SLC6A4) genes mediates the efficacy of several addiction treatments, such as ondansetron and disulfiram, and the antidepressants bupropion, nortriptyline and sertraline.
Topics: Genetic Variation; Humans; Serotonin; Serotonin Agents; Serotonin Plasma Membrane Transport Proteins; Substance-Related Disorders; Tryptophan Hydroxylase
PubMed: 26265436
DOI: 10.2217/pgs.15.72 -
Revista Paulista de Pediatria : Orgao... 2020To verify the occurrence of overweight in children and adolescents with phenylketonuria and to identify possible causal factors.
OBJECTIVE
To verify the occurrence of overweight in children and adolescents with phenylketonuria and to identify possible causal factors.
DATA SOURCES
A systematic review was performed in the SciELO, PubMed and VHL databases using the descriptors "Phenylketonurias", "Overweight", "Child" and "Adolescent". Original articles conducted with children and adolescents, published between 2008 and 2018 in Portuguese, English or Spanish languages were included.
DATA SYNTHESIS
A total of 16 articles were identified and, after screening procedures, 6 studies were selected for the review. Overweight in children and adolescents with phenylketonuria was a frequent occurence in the studies included in this review, ranging from 7.8 to 32.6%. The female sex was the most affected by the nutritional disorder. Furthermore, a high caloric intake combined with a lack of stimuli to practice physical activities were main factors associated with the excessive weight in the population of interest.
CONCLUSIONS
Excess weight can be considered a common outcome in children and adolescents with phenylketonuria. It is mainly caused by inadequate food consumption and sedentary lifestyle. The importance of early identification of nutritional disturbances in children and adolescents with phenylketonuria should be emphasized, in order to prevent associated chronic diseases and to promote health by encouraging continued healthy eating habits and the regular practice of physical exercises.
Topics: Adolescent; Age Factors; Body Mass Index; Child; Child, Preschool; Cross-Sectional Studies; Energy Intake; Feeding Behavior; Female; Humans; Infant; Male; Overweight; Pediatric Obesity; Phenylalanine Hydroxylase; Phenylketonurias; Prevalence; Retrospective Studies; Sedentary Behavior; Sex Factors; Young Adult
PubMed: 32159642
DOI: 10.1590/1984-0462/2020/38/2018201 -
British Journal of Clinical Pharmacology Jun 2020CYP2D6 genetic polymorphisms are associated with metoprolol pharmacokinetics. Whether the clinical response to metoprolol is also affected remains uncertain. (Meta-Analysis)
Meta-Analysis Review
AIMS
CYP2D6 genetic polymorphisms are associated with metoprolol pharmacokinetics. Whether the clinical response to metoprolol is also affected remains uncertain.
METHODS
We conducted a systematic review on the effects of CYP2D6 polymorphism on the clinical response to metoprolol. Searches were conducted using MEDLINE. Meta-analyses were performed on the impact of CYP2D6-inferred phenotypes on heart rate (HR) reduction, diastolic (DBP) and systolic (SBP) blood pressure reduction, average daily doses, all-type adverse events and bradycardia.
RESULTS
Our qualitative assessment indicated inconsistent results in individual studies and endpoints, but CYP2D6 poor metabolizers (PM) generally presented a greater reduction in HR. The meta-analysis of 15 studies, including a total of 1146 individuals, found a reduction in HR of 3 beats/min (P = .017), and of SBP and DBP by 3 mmHg (P = .0048) for PM compared to non-PM individuals using similar metoprolol doses. Bradycardia appeared more frequent by 4-fold for PM, although significant heterogeneity was observed regarding bradycardia, which limits the scope of this finding.
CONCLUSION
Patients without any CYP2D6 metabolic capacities appear to have increased reduction in DBP, HR and SBP during metoprolol treatment and may be at a higher risk of bradycardia compared to patients with active CYP2D6 phenotypes. Further prospective data are required to determine whether CYP2D6 is associated with clinical events in patients treated with metoprolol, as well as to demonstrate the clinical utility of an individualized approach of prescribing metoprolol using CYP2D6-inferred phenotypes.
Topics: Cytochrome P-450 CYP2D6; Genotype; Humans; Metoprolol; Phenotype; Polymorphism, Genetic
PubMed: 32090368
DOI: 10.1111/bcp.14247