Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications

MedComm, Journal Year: 2023, Volume and Issue: 4(3)

Published: May 2, 2023

Protein posttranslational modifications (PTMs) refer to the breaking or generation of covalent bonds on backbones amino acid side chains proteins and expand diversity proteins, which provides basis for emergence organismal complexity. To date, more than 650 types protein modifications, such as most well-known phosphorylation, ubiquitination, glycosylation, methylation, SUMOylation, short-chain long-chain acylation redox irreversible have been described, inventory is still increasing. By changing conformation, localization, activity, stability, charges, interactions with other biomolecules, PTMs ultimately alter phenotypes biological processes cells. The homeostasis important human health. Abnormal may cause changes in properties loss functions, are closely related occurrence development various diseases. In this review, we systematically introduce characteristics, regulatory mechanisms, functions health addition, therapeutic prospects diseases by targeting associated enzymes also summarized. This work will deepen understanding promote discovery diagnostic prognostic markers drug targets

Language: Английский

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Practical Clinical and Diagnostic Pathway for the Investigation of the Infertile Couple

Frontiers in Endocrinology, Journal Year: 2021, Volume and Issue: 11

Published: Jan. 19, 2021

Capsule This expert opinion summarizes current knowledge on risk factors for infertility and identifies a practical clinical diagnostic approach the male female partners of an infertile couple aimed to improve investigation management fertility problems. Background Infertility represents important growing health problem affecting up 16% couples worldwide. In most cases, male, female, or combined factor can be identified, different causes have been related this condition. However, there are no standardized guidelines clinical-diagnostic recommendations concerning sometimes lacking, incomplete, problematic apply. Objective The aim work is provide appropriate pathway designed by multidisciplinary-team experts. rationale based history physical examination then oriented basis initial investigations. could applied in order reduce variation practice Methods Prominent Italian experts main specialties committed ART procedures, including gynecologists, andrologists, embryologists, biologists, geneticists, oncologists, microbiologists, called “InfertilItaly group”, used available evidence develop position. Outcomes Starting from individuation principal that may influence females males both genders, group identified procedures using gradual obtain precise diagnosis effective therapeutic option, reducing invasive occasionally redundant procedures. Conclusions position provides suggests workflow couples. By step-by-step approach, care workers involved ART, individuate shared

Language: Английский

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The effectiveness of weight‐loss lifestyle interventions for improving fertility in women and men with overweight or obesity and infertility: A systematic review update of evidence from randomized controlled trials

Obesity Reviews, Journal Year: 2021, Volume and Issue: 22(12)

Published: Aug. 13, 2021

Summary Being overweight or obese can have a negative impact on fertility outcomes. This systematic review updates randomized controlled trial (RCT) findings the effectiveness of weight loss interventions in reducing and improving reproductive outcomes women men with obesity infertility. Eligible studies, published since last review, were identified by searching databases from March 20, 2016 until 31, 2020. RCTs involving any type lifestyle intervention considered. Eight aggregated seven included our previous review. Meta‐analyses revealed that to combined diet exercise more likely become pregnant, risk ratio (RR) = 1.87 (95% CI 1.20, 2.93) achieve live birth RR 2.20 1.23, 3.94), compared control groups who received no minimal intervention. pattern was not replicated trials where immediate access assisted technology (ART). No eligible identified. Data largely obtained small scale studies. Better designed, adequately powered, robust are needed better understand effect both men.

Language: Английский

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Sperm count is increased by diet-induced weight loss and maintained by exercise or GLP-1 analogue treatment: a randomized controlled trial

Human Reproduction, Journal Year: 2022, Volume and Issue: 37(7), P. 1414 - 1422

Published: April 20, 2022

Abstract STUDY QUESTION Does diet-induced weight loss improve semen parameters, and are these possible improvements maintained with sustained loss? SUMMARY ANSWER An 8-week low-calorie was associated improved sperm concentration count, which were after 1 year in men who loss. WHAT IS KNOWN ALREADY Obesity is impaired quality. Weight improves metabolic health obesity, but there a lack of knowledge on the acute long-term effects parameters. DESIGN, SIZE, DURATION This substudy obesity enrolled randomized, controlled, double-blinded trial (the S-LITE trial). The conducted between August 2016 November 2019. A total 56 included study assigned to an initial diet (800 kcal/day) followed by randomization 52 weeks either: placebo habitual activity (placebo), exercise training (exercise), Glucagon Like Peptide (GLP-1) analogue liraglutide (liraglutide) or combination (combination). PARTICIPANTS/MATERIALS, SETTING, METHODS Inclusion criteria delivered samples, 18 65 years age, body mass index 32 43 kg/m2, otherwise healthy. carried out at Hvidovre Hospital University Copenhagen, participants from Greater Copenhagen Area. We assessed parameters anthropometrics collected blood samples before (T0), dietary intervention (T1), (T2). MAIN RESULTS AND THE ROLE OF CHANCE lost average 16.5 kg (95% CI: 15.2–17.8) during diet, increased 1.49-fold 1.18–1.88, P < 0.01) count 1.41-fold 1.07–1.87, 0.01). These for loss, not regained weight. Semen volume, motility motile did change. LIMITATIONS, REASONS FOR CAUTION randomized controlled maintenance. Analysis preregistered explore maintenance definite inferences cannot be made. WIDER IMPLICATIONS FINDINGS shows that obesity. Our findings indicate either both as strategies may used maintain count. FUNDING/COMPETING INTEREST(S) work supported excellence grant Novo Nordisk Foundation (NNF16OC0019968), Challenge Programme Grant (NNF18OC0033754) Helsefonden. Center Basic Metabolic Research independent research centre partially funded unrestricted donation (NNF18CC0034900). Saxenda pens provided Nordisk. Cambridge Plan products Plan. E.A.: shareholder, employee ExSeed Health Ltd. Recipient Ltd listed Patents planned, issued pending Ltd; J.J.H.: consultant Eli Lilly A/S A/S. Lecture fees Listed Advocacy group Antag Therapeutics Bainan Biotech; S.M.: lecture Support attending meetings Advisory boards A/S; Sanofi Aventis Merck Sharp & Dohme. S.S.T.: recipient remaining authors have no conflicts interest declare. TRIAL REGISTRATION NUMBER approved Ethical Committee Capital Region Denmark (H-16027082) Danish Medicines Agency (EudraCT Number: 2015-005585-32). ClinicalTrials.gov identifier (NCT number): NCT04122716. DATE 11 May 2016. FIRST PATIENT’S ENROLMENT

Language: Английский

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Does an increase in adipose tissue ‘weight’ affect male fertility? A systematic review and meta‐analysis based on semen analysis performed using the WHO 2010 criteria

Andrology, Journal Year: 2023, Volume and Issue: 12(1), P. 123 - 136

Published: May 25, 2023

Abstract Introduction Obesity negatively impact on the metabolism of sex hormones, leading to reduced testosterone serum levels. However, how obesity could overall gonadal function, particularly male fertility, remained unclear so far. Objective To systematically review evidences regarding influence body weight excess sperm production. Methods A meta‐analysis was conducted, searching all prospective and retrospective observational studies reporting subjects older than 18 years old, with from overweight severe were considered. Only using V edition World Health Organization (WHO) manual for semen analysis interpretation No specific interventions Search focused comparing overweight/obese normal subjects. Results Twenty‐eight Total count progressive motility significantly lower in compared Meta‐regression analyses demonstrated that patients’ age impacted parameters. Similarly, obese men showed concentration, total number, motilities, morphology Reduced concentration influenced by age, smoking habit, varicocele, levels at meta‐regression analyses. Conclusions The potential fertility is increased weight, men. higher worst quantity/quality. This result comprehensively included among non‐communicable risk factor infertility, shedding new lights negative function.

Language: Английский

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Exploring the underlying mechanisms of obesity and diabetes and the potential of Traditional Chinese Medicine: an overview of the literature

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: Aug. 1, 2023

Obesity and diabetes are closely related metabolic disorders that have become major public health concerns worldwide. Over the past few decades, numerous studies explored underlying mechanisms of these identified various risk factors, including genetics, lifestyle, dietary habits. Traditional Chinese Medicine (TCM) has been increasingly recognized for its potential to manage obesity diabetes. Weight loss is difficult sustain, several diabetic therapies, such as sulfonylureas, thiazolidinediones, insulin, might make it harder lose weight. While lifestyle changes should be primary approach people interested in lowering weight, drugs also worth investigating. Since some newer glucose-lowering medications cause weight loss, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) sodium-glucose cotransporter 2 inhibitors (SGLT2i), additionally utilized or under consideration use anti-obesity drugs, frontier between medication appears shifting. This review provides an overview literature on prospect TCM their management. We discuss interventions, acupuncture, herbal medicine, therapy, effects health. highlight regulating gut microbiota, reducing inflammation, improving insulin sensitivity. The findings suggest may provide a promising preventing managing However, further well-designed needed confirm efficacy safety interventions elucidate action.

Language: Английский

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Obesity and male fertility disorders

Molecular Aspects of Medicine, Journal Year: 2024, Volume and Issue: 97, P. 101273 - 101273

Published: April 8, 2024

Often associated with obesity, male infertility represents a widespread condition that challenges the wellbeing of couple. In this article, we provide comprehensive and critical analysis studies exploring association between obesity reproductive function, to evaluate frequency association, establish effects increased body weight on conventional biofunctional sperm parameters infertility. an attempt find possible molecular markers in obese patients, numerous mechanisms responsible for overweight/obese patients are reviewed depth. These include obesity-related functional hypogonadism, insulin resistance, hyperinsulinemia, chronic inflammation, adipokines, irisin, gut hormones, microbiome, transcriptome. According meta-analytic evidence, excessive negatively influences health. This can occurr through broad array mechanisms. Some these not yet fully understood need be further elucidated future. A better understanding metabolic disorders spermatogenesis fertilizing capacity is very useful identifying new diagnostic designing therapeutic strategies clinical management

Language: Английский

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Dietary Antioxidants in the Treatment of Male Infertility: Counteracting Oxidative Stress

Biology, Journal Year: 2021, Volume and Issue: 10(3), P. 241 - 241

Published: March 20, 2021

Infertility affects about 15% of the population and male factors only are responsible for ~25–30% cases infertility. Currently, etiology suboptimal semen quality is poorly understood, many environmental genetic factors, including oxidative stress, have been implicated. Oxidative stress an imbalance between production free radicals, or reactive oxygen species (ROS), capacity body to counteract their harmful effects through neutralization by antioxidants. The purpose this review, employing joint expertise international researchers specialized in nutrition fertility areas, update knowledge reproductive consequences excessive ROS concentrations on Assisted Reproduction Techniques (ART) clinical outcomes, discuss role antioxidants finally why foods dietary patterns more innocuous long term solution ameliorating therefore results ART outcomes. Since a narrative review not systematic/meta-analysis, summarized information present study should be considered cautiously.

Language: Английский

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Body mass index and subfertility: multivariable regression and Mendelian randomization analyses in the Norwegian Mother, Father and Child Cohort Study

Human Reproduction, Journal Year: 2021, Volume and Issue: 36(12), P. 3141 - 3151

Published: Sept. 21, 2021

What is the association between BMI and subfertility?We observed a J-shaped relationship subfertility in both sexes, when using standard multivariable regression Mendelian randomization (MR) analysis.High women men associated with observational studies this further substantiated by few small randomized controlled trials of weight reduction success assisted reproduction. Women low also have lower conception rates reproduction technologies.Cohort study (the Norwegian Mother, Father Child Cohort Study), 28 341 26 252 men, recruited from all over Norway 1999 2008.Women (average age 30, average 23.1 kg/m2) 33, 25.5 had available genotype data provided self-reported information on time-to-pregnancy BMI. A total 10% couples were subfertile (time-to-pregnancy ≥12 months).Our findings support sexes logistic models. Non-linear MR validated relationship. 1 kg/m2 greater genetically predicted was linked to 18% odds (95% CI 5% 31%) obese (≥30.0 15% (-24% -2%) <20.0 kg/m2. higher 26% (8-48%) among men. Low values related risk at end distribution. 23 25 lowest respectively.The main limitations our that we did not know whether driven women, or both; exclusive consideration individuals northern European ancestry; limited amount participants obesity kg/m2.Our results causal effect Our expand current evidence indicating <20 may an increased subfertility. These suggest 20 are optimal for minimal subfertility.The MoBa Study supported Ministry Health Care Services Education Research. This project received funding Research Council under Union's Horizon 2020 research innovation program (grant agreement No 947684). It partly through its Centres Excellence scheme, number 262700. Open Access Folkehelseinstituttet/Norwegian Institute Public Health. D.A.L. UK National Senior Investigator (NF-SI-0611-10196) US Institutes (R01 DK10324) Advanced Grant (DevelopObese; 669545). The funders no role collection, analysis interpretation data; writing report; decision submit article publication. receives (or has last 10 years) International government charitable bodies, Roche Diagnostics Medtronic unrelated work. rest authors declare competing interests exist.N/A.

Language: Английский

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APHRODITE criteria: Addressing male patients with hypogonadism and/or infertility owing to altered idiopathic testicular function

Reproductive BioMedicine Online, Journal Year: 2023, Volume and Issue: 48(4), P. 103647 - 103647

Published: Oct. 29, 2023

Can a novel classification system of the infertile male - 'APHRODITE' (Addressing Patients with Hypogonadism and/or infeRtility Owing to altereD, Idiopathic TEsticular function) stratify different subgroups infertility help scientists design clinical trials on hormonal treatment infertility, and clinicians counsel treat endocrinological imbalances in men and, ultimately, increase chances natural assisted conception?

Language: Английский

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