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Sexual Medicine Reviews Jan 2021Testosterone prescriptions have increased dramatically in recent years, largely because of changes in expert guidelines. Concerns have been raised that testosterone... (Review)
Review
INTRODUCTION
Testosterone prescriptions have increased dramatically in recent years, largely because of changes in expert guidelines. Concerns have been raised that testosterone therapy (TTh) may be associated with an increased incidence of conditions such as cardiovascular (CV) disease, thromboembolic events, obstructive sleep apnea (OSA), benign prostatic hyperplasia (BPH), and prostate cancer (PCa) and also may be a beneficial therapy in the management of prediabetes. As such, considerable debate remains regarding which hypogonadal populations are appropriate candidates for TTh.
OBJECTIVES
This systematic review aims to affirm or refute, using the most current evidence, the published concerns surrounding TTh and its potential increased risk of conditions such as CV disease, thromboembolic events, OSA, urolithiasis, BPH, and PCa, as well as its role as a potential tool for managing prediabetes.
METHODS
A systematic review of literature surrounding TTh and its impact on increasing risk for the adverse conditions mentioned previously was performed. 62 publications were selected for inclusion based on their relevance to the effects and risks of TTh. Evidence is current through December 2019.
RESULTS
Evidence demonstrates that positive associations exist between TTh and OSA, erythrocytosis, as well as urolithiasis. TTh may potentially be used to treat hypogonadal men with prediabetes. While low testosterone is positively correlated with adverse CV events, TTh in hypogonadal men either has no effect or decreases such risk. TTh is likely not associated with increased risk of PCa incidence or recurrence.
CONCLUSIONS
Despite historical beliefs that TTh increases the risk of CV disease, thromboembolic events, BPH, and PCa, recent evidence suggests that TTh conveys less risk than previously perceived. While caution should continue to be exercised, evidence suggests that TTh is a reasonable treatment option in many hypogonadal men who were previously excluded from TTh based on risk factors and prior health histories. Twitchell DK, Pastuszak AW, Khera M. Controversies in Testosterone Therapy. Sex Med Rev 2021;9:149-159.
Topics: Hormone Replacement Therapy; Humans; Hypogonadism; Male; Polycythemia; Prostatic Neoplasms; Testosterone
PubMed: 33309270
DOI: 10.1016/j.sxmr.2020.09.004 -
Biotechnology Advances 2023Polyphenolic compounds (such as quercetin and resveratrol) possess potential medicinal values due to their various bioactivities, but poor water solubility hinders their... (Review)
Review
Polyphenolic compounds (such as quercetin and resveratrol) possess potential medicinal values due to their various bioactivities, but poor water solubility hinders their health benefits to humankind. Glycosylation is a well-known post-modification method to biosynthesize natural product glycosides with improved hydrophilicity. Glycosylation has profound effects on decreasing toxicity, increasing bioavailability and stability, together with changing bioactivity of polyphenolic compounds. Therefore, polyphenolic glycosides can be used as food additives, therapeutics, and nutraceuticals. Engineered biosynthesis provides an environmentally friendly and cost-effective approach to generate polyphenolic glycosides through the use of various glycosyltransferases (GTs) and sugar biosynthetic enzymes. GTs transfer the sugar moieties from nucleotide-activated diphosphate sugar (NDP-sugar) donors to sugar acceptors such as polyphenolic compounds. In this review, we systematically review and summarize the representative polyphenolic O-glycosides with various bioactivities and their engineered biosynthesis in microbes with different biotechnological strategies. We also review the major routes towards NDP-sugar formation in microbes, which is significant for producing unusual or novel glycosides. Finally, we discuss the trends in NDP-sugar based glycosylation research to promote the development of prodrugs that positively impact human health and wellness.
Topics: Humans; Glycosides; Carbohydrates; Glycosylation; Glycosyltransferases; Sugars; Nucleotides
PubMed: 37028465
DOI: 10.1016/j.biotechadv.2023.108146 -
Trends in Genetics : TIG Feb 2017Our understanding of gene expression has come far since the 'one-gene one-polypeptide' hypothesis proposed by Beadle and Tatum. In this review, we address the gradual... (Review)
Review
Our understanding of gene expression has come far since the 'one-gene one-polypeptide' hypothesis proposed by Beadle and Tatum. In this review, we address the gradual recognition that a growing number of polycistronic genes, originally discovered in viruses, are being identified within the mammalian genome, and that these may provide new insights into disease mechanisms and treatment. We carried out a systematic literature review identifying 13 mammalian genes for which there is evidence for polycistronic expression via translation through an internal ribosome entry site (IRES). Although the canonical mechanism of translation initiation has been studied extensively, here we highlight a process of noncanonical translation, IRES-mediated translation, that is a growing source for understanding complex inheritance, the elucidation of disease mechanisms, and the discovery of novel therapeutic targets. Identification of additional polycistronic genes may provide new insights into disease therapy and allow for new discoveries of both translational and disease mechanisms.
Topics: Animals; Genetic Diseases, Inborn; Humans; Internal Ribosome Entry Sites; Mammals; Molecular Targeted Therapy; Protein Biosynthesis; RNA, Messenger
PubMed: 28012572
DOI: 10.1016/j.tig.2016.11.007 -
Traffic (Copenhagen, Denmark) Dec 2021Endoplasmic reticulum (ER)-to-Golgi trafficking is an essential and highly conserved cellular process. The coat protein complex-II (COPII) arm of the trafficking... (Review)
Review
Endoplasmic reticulum (ER)-to-Golgi trafficking is an essential and highly conserved cellular process. The coat protein complex-II (COPII) arm of the trafficking machinery incorporates a wide array of cargo proteins into vesicles through direct or indirect interactions with Sec24, the principal subunit of the COPII coat. Approximately one-third of all mammalian proteins rely on the COPII-mediated secretory pathway for membrane insertion or secretion. There are four mammalian Sec24 paralogs and three yeast Sec24 paralogs with emerging evidence of paralog-specific cargo interaction motifs. Furthermore, individual paralogs also differ in their affinity for a subset of sorting motifs present on cargo proteins. As with many aspects of protein trafficking, we lack a systematic and thorough understanding of the interaction of Sec24 with cargoes. This systematic review focuses on the current knowledge of cargo binding to both yeast and mammalian Sec24 paralogs and their ER export motifs. The analyses show that Sec24 paralog specificity of cargo (and cargo receptors) range from exclusive paralog dependence or preference to partial redundancy. We also discuss how the Sec24 secretion system is hijacked by viral (eg, VSV-G, Hepatitis B envelope protein) and bacterial (eg, the enteropathogenic Escherichia coli type III secretion system effector NleA/EspI) pathogens.
Topics: Animals; COP-Coated Vesicles; Endoplasmic Reticulum; Golgi Apparatus; Mammals; Membrane Proteins; Protein Transport; Proteins; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Secretory Pathway
PubMed: 34533884
DOI: 10.1111/tra.12817 -
Biomolecules Mar 2024Cholesterol is an essential molecule of life, and its synthesis can be inhibited by both genetic and nongenetic mechanisms. Hundreds of chemicals that we are exposed to... (Review)
Review
Cholesterol is an essential molecule of life, and its synthesis can be inhibited by both genetic and nongenetic mechanisms. Hundreds of chemicals that we are exposed to in our daily lives can alter sterol biosynthesis. These also encompass various classes of FDA-approved medications, including (but not limited to) commonly used antipsychotic, antidepressant, antifungal, and cardiovascular medications. These medications can interfere with various enzymes of the post-lanosterol biosynthetic pathway, giving rise to complex biochemical changes throughout the body. The consequences of these short- and long-term homeostatic disruptions are mostly unknown. We performed a comprehensive review of the literature and built a catalogue of chemical agents capable of inhibiting post-lanosterol biosynthesis. This process identified significant gaps in existing knowledge, which fall into two main areas: mechanisms by which sterol biosynthesis is altered and consequences that arise from the inhibitions of the different steps in the sterol biosynthesis pathway. The outcome of our review also reinforced that sterol inhibition is an often-overlooked mechanism that can result in adverse consequences and that there is a need to develop new safety guidelines for the use of (novel and already approved) medications with sterol biosynthesis inhibiting side effects, especially during pregnancy.
Topics: Animals; Humans; Biosynthetic Pathways; Cholesterol; Lanosterol; Sterols
PubMed: 38672427
DOI: 10.3390/biom14040410 -
European Journal of Endocrinology Sep 2023Anorexia nervosa is a primary psychiatric disorder characterized by self-induced negative energy balance. A number of hormonal responses and adaptations occur in... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Anorexia nervosa is a primary psychiatric disorder characterized by self-induced negative energy balance. A number of hormonal responses and adaptations occur in response to starvation and low body weight including changes in adrenocortical hormones. Our objective was to systematically review adrenocortical hormone levels in anorexia nervosa.
DESIGN/METHODS
We searched MEDLINE and EMBASE for studies that reported at least one adrenocortical hormone, including dehydroepiandrosterone (DHEA), DHEA-sulphate (DHEA-S), progesterone, 17-hydroxyprogesterone, pregnenolone, cortisol (serum, urine, cerebrospinal fluid, and hair sample), aldosterone, androstenedione, and testosterone in patients with anorexia nervosa and normal-weight healthy controls from inception until October 2021. Means and standard deviations for each hormone were extracted from the studies to calculate a mean difference (MD). A pooled MD was then calculated by combining MDs of each study using the random-effects model.
RESULTS
We included a total of 101 studies with over 2500 females with anorexia nervosa. Mean cortisol levels were significantly higher in anorexia nervosa as compared to normal-weight controls for multiple forms of measurement, including morning cortisol, 12-hour and 24-hour pooled serum cortisol, 24-hour urine cortisol, and after an overnight dexamethasone suppression test. In contrast, mean serum total testosterone and DHEA-S levels were significantly lower among patients with anorexia nervosa.
CONCLUSIONS
Women with anorexia nervosa have higher cortisol levels and lower DHEA-S and testosterone levels compared to women without anorexia nervosa. This finding is important to consider when evaluating low-weight women for disorders involving the adrenal axis, especially Cushing's syndrome.
Topics: Humans; Female; Anorexia Nervosa; Hydrocortisone; Aldosterone; Progesterone; Dehydroepiandrosterone Sulfate
PubMed: 37669399
DOI: 10.1093/ejendo/lvad123 -
Wiley Interdisciplinary Reviews. RNA Nov 2021In the last decade, an intriguing new paradigm of regulation has emerged in which some transcripts longer than 200 nucleotides and no coding potential, long noncoding... (Review)
Review
In the last decade, an intriguing new paradigm of regulation has emerged in which some transcripts longer than 200 nucleotides and no coding potential, long noncoding RNA (lncRNAs), exhibit the capability to control posttranslational modifications of nonhistone proteins in both invertebrates and vertebrates. The extent of such a regulation is still largely unknown. We performed a systematic review to identify and evaluate the potential impact of lncRNA-dependent methylation of nonhistone proteins. Collectively, these lncRNAs primarily act as scaffolds upon which methyltransferases (MTases) and targets are brought in proximity. In this manner, the N-MTase activity of EZH2, protein arginine-MTase 1/4/5, and SMYD2 is exploited to modulate the stability or the compartmentalization of several nonhistone proteins with roles in cell signaling, gene expression, and RNA processing. Moreover, these lncRNAs can indirectly affect the methylation of nonhistone proteins by transcriptional or posttranscriptional regulation of MTases. Strikingly, the lncRNAs/MTases/nonhistone proteins networking seem to be relevant to carcinogenesis and neurological disorders. This article is categorized under: Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs.
Topics: Animals; Gene Expression Regulation; Methylation; Protein Processing, Post-Translational; RNA Processing, Post-Transcriptional; RNA, Long Noncoding
PubMed: 33913612
DOI: 10.1002/wrna.1661 -
European Geriatric Medicine Jun 2022We conducted a systematic review to evaluate the relationship between total testosterone (TT), free testosterone (fT), or sex hormone-binding globulin (SHBG) and frailty... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
We conducted a systematic review to evaluate the relationship between total testosterone (TT), free testosterone (fT), or sex hormone-binding globulin (SHBG) and frailty in older adults.
METHODS
We systematically searched nine databases (e.g. MEDLINE, Embase, ACP Journal Club, and the Cochrane library et al.) for papers on frailty and androgen levels published up to October 10, 2021. We calculated the odds ratio (OR) for the relationship between testosterone level and frailty by performing meta-analysis.
RESULTS
The search strategy yielded 311 hits in all databases combined. Eleven (seven cross-sectional studies and four cohort studies) met the inclusion criteria for meta-analysis. Among cross-sectional studies, meta-analysis revealed a significant association between TT and frailty in men (OR = 1.37 [95% CI 1.09, 1.72]) not women (OR = 1.06 [0.84, 1.34]). The fT was also significantly association with frailty in men (OR = 1.55 [1.06, 2.25] not women (OR = 1.35 [0.91, 2.01]). Cohort studies showed the same result in TT (OR = 1.09 [1.02, 1.18]) and fT (OR = 1.15 [1.02, 1.30]) for men. We did not find a significant association between SHBG and frailty.
CONCLUSION
The findings of this systematic review and meta-analysis suggest that TT and fT were significantly associated with frailty in older men but not women.
Topics: Aged; Cohort Studies; Cross-Sectional Studies; Frailty; Humans; Male; Odds Ratio; Testosterone
PubMed: 35107811
DOI: 10.1007/s41999-022-00614-8 -
Obstetrics and Gynecology Sep 2023To systematically review the literature and provide clinical practice guidelines regarding various nonestrogen therapies for treatment of genitourinary syndrome of...
OBJECTIVE
To systematically review the literature and provide clinical practice guidelines regarding various nonestrogen therapies for treatment of genitourinary syndrome of menopause (GSM).
DATA SOURCES
MEDLINE, EMBASE, ClinicalTrials.gov , and Cochrane databases were searched from inception to July 2021. We included comparative and noncomparative studies. Interventions and comparators were limited to seven products that are commercially available and currently in use (vaginal dehydroepiandrosterone [DHEA], ospemifene, laser or energy-based therapies, polycarbophil-based vaginal moisturizer, Tibolone, vaginal hyaluronic acid, testosterone). Topical estrogen, placebo, other nonestrogen products, as well as no treatment were considered as comparators.
METHODS OF STUDY SELECTION
We double-screened 9,131 abstracts and identified 136 studies that met our criteria. Studies were assessed for quality and strength of evidence by the systematic review group.
TABULATION, INTEGRATION, AND RESULTS
Information regarding the participants, details on the intervention and comparator and outcomes were extracted from the eligible studies. Alternative therapies were similar or superior to estrogen or placebo with minimal increase in adverse events. Dose response was noted with vaginal DHEA and testosterone. Vaginal DHEA, ospemifene, erbium and fractional carbon dioxide (CO 2 ) laser, polycarbophil-based vaginal moisturizer, tibolone, hyaluronic acid, and testosterone all improved subjective and objective signs of atrophy. Vaginal DHEA, ospemifene, tibolone, fractional CO 2 laser, polycarbophil-based vaginal moisturizer, and testosterone improved sexual function.
CONCLUSION
Most nonestrogen therapies are effective treatments for the various symptoms of GSM. There are insufficient data to compare nonestrogen options to each other.
Topics: Female; Humans; Hyaluronic Acid; Menopause; Vagina; Estrogens; Testosterone; Dehydroepiandrosterone
PubMed: 37543737
DOI: 10.1097/AOG.0000000000005288 -
Environmental Science and Pollution... Sep 2022Worldwide use of glyphosate is constantly increasing and its residues are detected in drinking water, agriculture, and food products. There are controversial data... (Meta-Analysis)
Meta-Analysis Review
Worldwide use of glyphosate is constantly increasing and its residues are detected in drinking water, agriculture, and food products. There are controversial data regarding the potential reproductive adverse effects of glyphosate herbicide. Therefore, we conducted a systematic review and meta-analysis on the studies in which the alteration of at least one sexual hormone including testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol was reported as a measured outcome in rats. In November 2020, 284 articles were screened, of which eight were eligible for the meta-analysis. An overall considerable effect of glyphosate exposure was found on decreasing of testosterone (7 studies, WMD = - 1.48 ng/mL; 95% CI, - 2.34 to - 0.61; P = 0.001), LH (3 studies, WMD = - 2.03 mIu/mL; 95% CI, - 3.34 to - 0.71; P = 0.003), and FSH (3 studies, WMD = - 2.28 mIu/mL; 95% CI, - 5.12 to 0.55; P = 0.115). According to our results, glyphosate intake could have major effects on the health of reproductive system. Consequently, strict monitoring of the residual glyphosate content in the drinking water, agricultural crops, and food products is necessary.
Topics: Animals; Drinking Water; Follicle Stimulating Hormone; Glycine; Luteinizing Hormone; Rats; Testosterone; Glyphosate
PubMed: 34453247
DOI: 10.1007/s11356-021-16145-x