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Biochemical Pharmacology Sep 2023Lipid and glucose metabolism are critical for human activities, and their disorders can cause diabetes and obesity, two prevalent metabolic diseases. Studies suggest... (Review)
Review
Lipid and glucose metabolism are critical for human activities, and their disorders can cause diabetes and obesity, two prevalent metabolic diseases. Studies suggest that the bone involved in lipid and glucose metabolism is emerging as an endocrine organ that regulates systemic metabolism through bone-derived molecules. Sclerostin, a protein mainly produced by osteocytes, has been therapeutically targeted by antibodies for treating osteoporosis owing to its ability to inhibit bone formation. Moreover, recent evidence indicates that sclerostin plays a role in lipid and glucose metabolism disorders. Although the effects of sclerostin on bone have been extensively examined and reviewed, its effects on systemic metabolism have not yet been well summarized. In this paper, we provide a systemic review of the effects of sclerostin on lipid and glucose metabolism based on in vitro and in vivo evidence, summarize the research progress on sclerostin, and prospect its potential manipulation for obesity and diabetes treatment.
Topics: Humans; Proteins; Glucose Metabolism Disorders; Obesity; Glucose; Lipids
PubMed: 37481136
DOI: 10.1016/j.bcp.2023.115694 -
Drug Metabolism Reviews Nov 2023Nebivolol is a beta-1 receptor blocker used to treat hypertension, heart failure, erectile dysfunction, vascular disease, and diabetes mellitus. This review investigated... (Review)
Review
Nebivolol is a beta-1 receptor blocker used to treat hypertension, heart failure, erectile dysfunction, vascular disease, and diabetes mellitus. This review investigated the data regarding pharmacokinetic (PK) parameters, drug-drug interactions, dextrorotatory (D), and levorotatory (L) stereoisomers of nebivolol. The articles related to the PK of nebivolol were retrieved by searching the five databases; Google Scholar, PubMed, Cochrane Library, ScienceDirect, and EBSCO. A total of 20 studies comprising plasma concentration-time profile data following the nebivolol's oral and intravenous (IV) administration were included. The area under the concentration-time curve from zero to infinity (AUC) was 15 times greater in poor metabolizers (PMs) than in extensive metabolizers (EMs). In hypertensive patients, L-nebivolol expressed a higher maximum plasma concentration (C) than D-nebivolol, i.e. 2.5 ng/ml vs 1.2 ng/ml. The AUC of nebivolol was 3-fold greater in chronic kidney disease (CKD). The clearance (CL) was increased in obese than in controls from 51.6 ± 11.6 L/h to 71.6 ± 17.4 L/h when 0.5 mg/ml IV solution was infused. Nebivolol showed higher C, AUC and half-life (t) when co-administered with bupropion, duloxetine, fluvoxamine, paroxetine, lansoprazole, and fluoxetine. This concise review of nebivolol would be advantageous in assessing all PK parameters, which may be crucial for clinicians to avoid drug-drug interactions, prevent adverse drug events and optimize the dosage regimen in diseased patients diagnosed with hypertension and cardiovascular disorders.
Topics: Male; Humans; Nebivolol; Hypertension; Fluvoxamine; Lansoprazole; Drug Interactions
PubMed: 37849071
DOI: 10.1080/03602532.2023.2271195 -
International Clinical... Jul 2023The whole picture of psychotropics for bipolar depression (BPD) remains unclear. This review compares the differences in efficacy and safety profiles among common...
The whole picture of psychotropics for bipolar depression (BPD) remains unclear. This review compares the differences in efficacy and safety profiles among common psychotropics for BPD. MEDLINE, EMBASE, and PsycINFO were searched for proper studies. The changes in the depressive rating scale, remission/response rates, nervous system adverse events (NSAEs), gastrointestinal adverse events (GIAEs), metabolic parameters, and prolactin were compared between medication and placebo or among medications with the Cohen's d or number needed to treat/harm. The search provided 10 psychotropics for comparison. Atypical antipsychotics (AAPs) were superior to lithium and lamotrigine at alleviating acute depressive symptoms. Lithium was more likely to induce dry mouth and nausea. Cariprazine and aripiprazole seemed to be associated with an increased risk of akathisia and upper GIAEs. Lurasidone was associated with an increased risk of developing akathisia and hyperprolactinemia. Olanzapine, olanzapine-fluoxetine combination (OFC), and quetiapine were associated with an increased risk of NSAEs, metabolic risk, dry mouth, and constipation. Cariprazine, lurasidone, OFC, or quetiapine was optimal monotherapy for BPD. Further studies are needed to assess the efficacy and safety of lamotrigine for treating BPD. Adverse events varied widely across different drug types due to variations in psychopharmacological mechanisms, dosages, titration, and ethnicities.
Topics: Humans; Antipsychotic Agents; Bipolar Disorder; Lurasidone Hydrochloride; Quetiapine Fumarate; Lamotrigine; Lithium; Psychomotor Agitation; Antimanic Agents
PubMed: 36947416
DOI: 10.1097/YIC.0000000000000449 -
International Journal of Molecular... Dec 2023Substance addiction is a chronic and relapsing brain disorder characterized by compulsive seeking and continued substance use, despite adverse consequences. The high... (Review)
Review
Substance addiction is a chronic and relapsing brain disorder characterized by compulsive seeking and continued substance use, despite adverse consequences. The high prevalence and social burden of addiction are indisputable; however, the available intervention is insufficient. The modulation of gene expression and aberrant adaptation of neural networks are attributed to the changes in brain functions under repeated exposure to addictive substances. Considerable studies have demonstrated that miRNAs are strong modulators of post-transcriptional gene expression in substance addiction. The emerging role of microRNA (miRNA) provides new insights into many biological and pathological processes in the central nervous system: their variable expression in different regions of the brain and tissues may play a key role in regulating the pathophysiological events of addiction. This work provides an overview of the current literature on miRNAs involved in addiction, evaluating their impaired expression and regulatory role in neuroadaptation and synaptic plasticity. Clinical implications of such modulatory capacities will be estimated. Specifically, it will evaluate the potential diagnostic role of miRNAs in the various stages of drug and substance addiction. Future perspectives about miRNAs as potential novel therapeutic targets for substance addiction and abuse will also be provided.
Topics: Humans; MicroRNAs; Substance-Related Disorders; Behavior, Addictive; Brain
PubMed: 38069445
DOI: 10.3390/ijms242317122 -
European Journal of Medicinal Chemistry Dec 2023Targeted protein degradation (TPD) has emerged as a promising therapeutic approach with potential advantages over traditional occupancy-based inhibitors in terms of... (Review)
Review
Targeted protein degradation (TPD) has emerged as a promising therapeutic approach with potential advantages over traditional occupancy-based inhibitors in terms of dosing, side effects and targeting "undruggable" proteins. Targeted degraders can theoretically bind any nook or cranny of targeted proteins to drive degradation. This offers convenience versus the small-molecule inhibitors that must function in a well-defined pocket. The degradation process depends mainly on two cell self-destruction mechanisms, namely the ubiquitin-proteasome system and the lysosomal degradation pathway. Various TPD strategies (e.g., proteolytic-targeting chimeras, molecular glues, lysosome-targeting chimeras, and autophagy-targeting chimeras) have been developed. These approaches hold great potential for targeting dysregulated proteins, potentially offering therapeutic benefits. In this article, we systematically review the mechanisms of various TPD strategies, potential applications to drug discovery, and recent advances. We also discuss the benefits and challenges associated with these TPD strategies, aiming to provide insight into the targeting of dysregulated proteins and facilitate their clinical applications.
Topics: Proteolysis; Proteasome Endopeptidase Complex; Autophagy; Drug Discovery; Lysosomes
PubMed: 37778240
DOI: 10.1016/j.ejmech.2023.115839 -
Phytotherapy Research : PTR Nov 2023Cardiovascular diseases are currently the primary cause of mortality in the whole world. Growing evidence indicated that the disturbances in cardiac fatty acid... (Review)
Review
Cardiovascular diseases are currently the primary cause of mortality in the whole world. Growing evidence indicated that the disturbances in cardiac fatty acid metabolism are crucial contributors in the development of cardiovascular diseases. The abnormal cardiac fatty acid metabolism usually leads to energy deficit, oxidative stress, excessive apoptosis, and inflammation. Targeting fatty acid metabolism has been regarded as a novel approach to the treatment of cardiovascular diseases. However, there are currently no specific drugs that regulate fatty acid metabolism to treat cardiovascular diseases. Many traditional Chinese medicines have been widely used to treat cardiovascular diseases in clinics. And modern studies have shown that they exert a cardioprotective effect by regulating the expression of key proteins involved in fatty acid metabolism, such as peroxisome proliferator-activated receptor α and carnitine palmitoyl transferase 1. Hence, we systematically reviewed the relationship between fatty acid metabolism disorders and four types of cardiovascular diseases including heart failure, coronary artery disease, cardiac hypertrophy, and diabetic cardiomyopathy. In addition, 18 extracts and eight monomer components from traditional Chinese medicines showed cardioprotective effects by restoring cardiac fatty acid metabolism. This work aims to provide a reference for the finding of novel cardioprotective agents targeting fatty acid metabolism.
Topics: Humans; Cardiovascular Diseases; Heart; Medicine, Chinese Traditional; PPAR alpha; Fatty Acids; Energy Metabolism
PubMed: 37533230
DOI: 10.1002/ptr.7965 -
PloS One 2023Diabetic kidney disease (DKD) is a health burden of rising importance. Slowing progression to end stage kidney disease is the main goal of drug treatment. The aim of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Diabetic kidney disease (DKD) is a health burden of rising importance. Slowing progression to end stage kidney disease is the main goal of drug treatment. The aim of this analysis is to compare drug treatments of DKD by means of a systemic review and a network meta-analysis.
METHODS
We searched Medline, CENTRAL and clinicaltrials.gov for randomized, controlled studies including adults with DKD treated with the following drugs of interest: single angiotensin-converting-enzyme-inhibitor or angiotensin-receptor-blocker (single ACEi/ARB), angiotensin-converting-enzyme-inhibitor and angiotensin-receptor-blocker combination (ACEi+ARB combination), aldosterone antagonists, direct renin inhibitors, non-steroidal mineralocorticoid-receptor-antagonists (nsMRA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i). As primary endpoints, we defined: overall mortality and end-stage kidney disease, as secondary endpoints: renal composite outcome and albuminuria and as safety endpoints: acute kidney injury, hyperkalemia and hypotension. Under the use of a random effects model, we computed the overall effect estimates using the statistic program R4.1 and the corresponding package "netmeta". Risk of bias was assessed using the RoB 2 tool and the quality of evidence of each pairwise comparison was rated according to GRADE (Grading of Recommendations Assessment, Development and Evaluation).
RESULTS
Of initial 3489 publications, 38 clinical trials were found eligible, in total including 42346 patients. Concerning the primary endpoints overall mortality and end stage kidney disease, SGLT2i on top of single ACEi/ARB compared to single ACEi/ARB was the only intervention significantly reducing the odds of mortality (OR 0.81, 95%CI 0.70-0.95) and end-stage kidney disease (OR 0.69, 95%CI 0.54-0.88). The indirect comparison of nsMRA vs SGLT2i in our composite endpoint suggests a superiority of SGLT2i (OR 0.60, 95%CI 0.47-0.76). Concerning safety endpoints, nsMRA and SGLT2i showed benefits compared to the others.
CONCLUSIONS
As the only drug class, SGLT2i showed in our analysis beneficial effects on top of ACEi/ARB treatment regarding mortality and end stage kidney disease and by that reconfirmed its position as treatment option for diabetic kidney disease. nsMRA reduced the odds for a combined renal endpoint and did not raise any safety concerns, justifying its application.
Topics: Adult; Humans; Angiotensin-Converting Enzyme Inhibitors; Diabetic Nephropathies; Angiotensin Receptor Antagonists; Network Meta-Analysis; Sodium-Glucose Transporter 2 Inhibitors; Kidney Failure, Chronic; Angiotensins; Diabetes Mellitus
PubMed: 37917640
DOI: 10.1371/journal.pone.0293183 -
Journal of Psychiatric Research Aug 2023Rapid-cycling in bipolar disorder (RC-BD) is associated with greater illness morbidity and inferior treatment response but many aspects remain unclear, prompting this... (Review)
Review
Rapid-cycling in bipolar disorder (RC-BD) is associated with greater illness morbidity and inferior treatment response but many aspects remain unclear, prompting this systematic review of its definitions, prevalence, and clinical characteristics. We searched multiple literature databases through April 2022 for systematic reviews or meta-analyses on RC-BD and extracted associated definitions, prevalence, risk-factors, and clinical outcomes. We assessed study quality (NIH Quality Assessment Tool) and levels of evidence (Oxford criteria). Of 146 identified reviews, 22 fulfilling selection criteria were included, yielding 30 studies involving 13,698 BD patients, of whom 3777 (27.6% [CI: 26.8-28.3]) were considered RC-BD, as defined in 14 reports by ≥4 recurrences/year within the past 12 months or in any year, without considering responsiveness to treatment. Random-effects meta-analytically pooled one-year prevalence was 22.3% [CI: 14.4-32.9] in 12 reports and lifetime prevalence was 35.5% [27.6-44.3] in 18 heterogenous reports. Meta-regression indicated greater lifetime prevalence of RC-BD among women than men (p=0.003). Association of RC-BD with suicide attempts, and unsatisfactory response to mood-stabilizers was supported by strong evidence (Level 1); associations with childhood maltreatment, mixed-features, female sex, and type-II BD had moderate evidence (Level 2). Other factors: genetic predisposition, metabolic disturbances or hypothyroidism, antidepressant exposure, predominant depressive polarity (Level 3), along with greater illness duration and immune-inflammatory dysfunction (Level 4) require further study. RC-BD was consistently recognized as having high prevalence (22.3%-35.5% of BD cases) and inferior treatment response. Identified associated factors can inform clinical practice. Long-term illness-course, metabolic factors, and optimal treatment require further investigation.
Topics: Female; Humans; Male; Antidepressive Agents; Bipolar Disorder; Hypothyroidism; Prevalence; Systematic Reviews as Topic; Meta-Analysis as Topic
PubMed: 37429185
DOI: 10.1016/j.jpsychires.2023.06.021 -
Nutrients Aug 2023Studies indicate a high prevalence of vitamin D deficiency in both the general population and at-risk groups. Given the association between vitamin D deficiency and... (Review)
Review
INTRODUCTION
Studies indicate a high prevalence of vitamin D deficiency in both the general population and at-risk groups. Given the association between vitamin D deficiency and various diseases, addressing this concern becomes crucial, especially in situations where routine monitoring is challenging.
MATERIALS AND METHODS
A systematic literature review of the current knowledge on vitamin D dosing in diverse at-risk populations and the application of the findings to a broader clinical perspective.
RESULTS
The reviewed studies revealed a high prevalence of vitamin D deficiency among patients with musculoskeletal disorders, systemic connective tissue diseases, corticosteroid use, endocrine and metabolic conditions, malabsorption syndromes, obesity, chronic kidney disease, cancer, and central nervous system diseases. Vitamin D deficiency was often more severe compared to the general population. Higher dosages of vitamin D beyond the recommended levels for the general population were shown to be effective in improving vitamin D status in these at-risk individuals. Additionally, some studies suggested a potential link between intermittent vitamin D administration and improved adherence.
CONCLUSION
Simplified dosing could empower clinicians to address vitamin D deficiency, particularly in high-risk populations, even without routine monitoring. Further research is needed to establish the optimal dosing regimens for specific at-risk populations.
Topics: Humans; Vitamin D; Vitamins; Vitamin D Deficiency; Knowledge; Malabsorption Syndromes
PubMed: 37686757
DOI: 10.3390/nu15173725 -
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