Epigenetics-targeted drugs: current paradigms and future challenges

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Ноя. 26, 2024

Epigenetics governs a chromatin state regulatory system through five key mechanisms: DNA modification, histone RNA remodeling, and non-coding regulation. These mechanisms their associated enzymes convey genetic information independently of base sequences, playing essential roles in organismal development homeostasis. Conversely, disruptions epigenetic landscapes critically influence the pathogenesis various human diseases. This understanding has laid robust theoretical groundwork for developing drugs that target epigenetics-modifying pathological conditions. Over past two decades, growing array small molecule targeting such as methyltransferase, deacetylase, isocitrate dehydrogenase, enhancer zeste homolog 2, have been thoroughly investigated implemented therapeutic options, particularly oncology. Additionally, numerous epigenetics-targeted are undergoing clinical trials, offering promising prospects benefits. review delineates epigenetics physiological contexts underscores pioneering studies on discovery implementation drugs. include inhibitors, agonists, degraders, multitarget agents, aiming to identify practical challenges avenues future research. Ultimately, this aims deepen epigenetics-oriented strategies further application settings.

Язык: Английский

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Predictive and Explainable Artificial Intelligence for Weight Loss After Sleeve Gastrectomy: Insights from Wide and Deep Learning with Medical Image and Non-Image Data

Applied Sciences, Год журнала: 2025, Номер 15(5), С. 2457 - 2457

Опубликована: Фев. 25, 2025

There has been no feasible approach for predicting weight loss after bariatric surgery. This study develops wide and deep learning (WAD), a predictive explainable artificial intelligence sleeve gastrectomy with medical image non-image data, such as electronic records (EMRs). Prospective data came from 42 patients at university hospital. They were followed one year The dependent variable consisted of three categories: minimal, moderate, significant change groups, classified based on postoperative percentage total (%TWL) in body mass index. A pair 100 images their each patient, 4200 pairs total. WAD model was trained tested 3200 1000 pairs, respectively. Here, the combined convolutional neural network (CNN) linear layer (EMR). population included patients, mean age 36.6 years (standard deviation SD 11.0) female proportion 58% (26/45). On average, %TWL 19.1 (SD 2.8), 27.3 2.2), 35.1 4.7) corresponding accuracy outcomes 61%, 100%, 75% groups (average 71%). When minimal moderate combined, 100% group group, an overall average 88%. Baseline HOMA2-B, insulin, vitamin B12 major predictors %TWL. optimal region interest found to be entire cross-section above diaphragm. In conclusion, is effective following data. most important identified baseline levels, while key (ROI) abdominal CT imaging located

Язык: Английский

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Impact of Metabolic Syndrome on Adiponectin, Cardio-Ankle Vascular Index, and Cardiovascular Risk in Middle-Aged Obese Men: A Cross-Sectional Study

Опубликована: Янв. 1, 2025

This study determined the impact of metabolic syndrome (MetS) on cardiovascular disease (CVD) risk in obese men by assessing adiponectin levels, cardio-ankle vascular index (CAVI), and 10-year atherosclerotic using Thai score (TCVRS), evaluated whether CAVI can be predictors for CVD. Among 82 middle-aged men, 70.7% had MetS, 56.1% hypoadiponectinemia, 20.7% were classified as having a high (>8), 15.9% considered at (TCVRS ≥ 20%). Compared with non-MetS group, participants MetS group higher CVD risk, evidenced significantly lower levels TCVRS. However, values did not differ significantly. components triglyceride low HDL-cholesterol affected while fasting plasma glucose impacted values, consistent Spearman correlation analysis. Additionally, positively correlated TCVRS was found to an independent predictor both total groups. In contrast, exhibited inverse group. Notably, subgroup analysis indicated that without hypoadiponectinemia highest TCVRS, over half which should monitored.

Язык: Английский

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Impact of metabolic syndrome on adiponectin, cardio-ankle vascular index, and cardiovascular risk in middle-aged obese men: a cross-sectional study

Human Nutrition & Metabolism, Год журнала: 2025, Номер unknown, С. 200309 - 200309

Опубликована: Март 1, 2025

Язык: Английский

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Transcriptome analysis of corpora lutea in domestic cats (Felis catus) reveals strong differences in gene expression of various hormones, hormone receptors and regulators across different developmental stages

BMC Genomics, Год журнала: 2025, Номер 26(1)

Опубликована: Март 31, 2025

Язык: Английский

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Joint association of triglyceride glucose index (TyG) and body roundness index (BRI) with stroke incidence: a national cohort study

Cardiovascular Diabetology, Год журнала: 2025, Номер 24(1)

Опубликована: Апрель 16, 2025

Abstract Background Insulin resistance (IR), as quantified by the triglyceride glucose (TyG) index, and visceral obesity, assessed body roundness index (BRI), have been identified pivotal risk factors for stroke. However, combined impact of these two indicators on stroke has not thoroughly investigated. This study aims to investigate both separate associations, well potential interactions, between TyG and/or BRI with respect incidence. Methods cohort encompassed 6621 respondents who were free at baseline from China Health Retirement Longitudinal Study (CHARLS). Participants categorized based median values or/and BRI. Cox proportional hazards regression models employed examine associations alone, their effects Both additive multiplicative interaction further estimated. Results Among participants aged 45 years or older, mean (SD) age was 58.06 (8.57) years, 2951 (44.6%) being male. During a follow-up period up 9 743 individuals experienced events. Compared low BRI, adjusted hazard ratios (HRs) follows: 1.36 (95% confidence interval [CI] 1.05–1.75) high 1.61 CI 1.27–2.05) 1.78 1.40–2.26) Neither nor interactions incident statistically significant. The combination enhanced predictive capability compared either biomarker alone. Conclusion We discovered that are strongly associated joint assessment enhances stroke, underscoring critical role IR adiposity in identification screening risk. Graphical abstract

Язык: Английский

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Pharmacological Blocking of Adiponectin Receptors Induces Alzheimer’s Disease-like Neuropathology and Impairs Hippocampal Function

Biomedicines, Год журнала: 2025, Номер 13(5), С. 1056 - 1056

Опубликована: Апрель 27, 2025

Background/Objectives: Previous studies have shown that adiponectin deficiency or blocking receptors (AdipoRs) in the brain can lead to an Alzheimer’s disease (AD)-like neuropathology. While AdipoRs are abundantly expressed peripheral tissues, effects of these tissues on unclear. This study investigates impacts with a administration ADP400, antagonist peptide targets cognitive performance, hippocampal adult neurogenesis, and AD-like neuropathology mice. Methods: Adult mice were intraperitoneally administered ADP400 blocks continuously for 21 days, followed by battery behavioral test mood memory performance. Results: ADP400-treated exhibited impaired performance increased anxiety-like behaviors. Molecular analyses revealed heightened hyperphosphorylation tau β-amyloid levels, alongside decreased expression PP2A hippocampus, suggesting critical role Furthermore, treatment significantly reduced as indicated BrdU, Ki67, DCX staining. Inhibiting could accumulated levels. Conclusions: These findings highlight manipulation modulating function offering insights into potential therapeutic strategies AD related disorders.

Язык: Английский

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Heterocyclic Betanin from Opuntia stricta var. Dillenii: Purification, Stability, and Effects on Carbohydrate Digestion, Absorption, Metabolism, and Enzyme Inhibition in Obese Rats with Type 2 Diabetes

Food Bioscience, Год журнала: 2025, Номер unknown, С. 106569 - 106569

Опубликована: Апрель 1, 2025

Язык: Английский

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Reevaluating Adiponectin’s impact on obesity hypertension: a Chinese case-control study

BMC Cardiovascular Disorders, Год журнала: 2024, Номер 24(1)

Опубликована: Апрель 13, 2024

Abstract Background Obesity and hypertension are major risk factors for cardiovascular diseases that affect millions of people worldwide. Both conditions associated with chronic low-grade inflammation, which is mediated by adipokines such as adiponectin. Adiponectin the most abundant adipokine has a beneficial impact on metabolic vascular biology, while high serum concentrations some syndromes. This “adiponectin paradox” still needs to be clarified in obesity-associated hypertension. The aim this study was investigate how adiponectin affects blood pressure, function obesity using Chinese adult case-control study. Methods A had finished recruiting 153 subjects divided four characteristic groups. levels were tested ELISA these among physical examination Waist circumference (WC), body mass index (BMI), systolic pressure (SB), diastolic (DB), other clinical laboratory data collected. Analyzation correlations between research differences groups done SPSS. Results Serum the| normal healthy group (NH group) significantly higher than those newly diagnosed untreated just-obesity (JO group), negatively correlated visceral adiposity index. With multiple linear egression analysis, it found that, adiponectin, gender, albumin (ALB), alanine aminotransferase (ALT) high-density lipoprotein cholesterol (HDLC) significant independent correlates, SB, age HDLC DB, alkaline phosphatase (ALP) correlate. variables did not reach significance model. Conclusions Our reveals adiponectin’s role obesity-hypertension multifaceted influenced systemic homeostasis signaling axis. In obesity-related hypertension, compensatory effects, resistance, reduced clearance from impaired kidneys liver all contribute paradox”.

Язык: Английский

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Alleviation of lipid metabolic dysfunction through regulation of intestinal bacteriophages and bacteria by green tea polyphenols in Ob/Ob mice

Food Chemistry, Год журнала: 2024, Номер 456, С. 139988 - 139988

Опубликована: Июнь 5, 2024

Язык: Английский

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