In vitro biological studies and computational prediction-based analyses of pyrazolo[1,5-a]pyrimidine derivatives

RSC Advances, Journal Year: 2024, Volume and Issue: 14(12), P. 8397 - 8408

Published: Jan. 1, 2024

Recently, new pharmaceutical discoveries have become very important for addressing diverse health problems and protecting humanity.

Language: Английский

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The Multifaceted S100B Protein: A Role in Obesity and Diabetes?

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(2), P. 776 - 776

Published: Jan. 8, 2024

The S100B protein is abundant in the nervous system, mainly astrocytes, and also present other districts. Among these, adipose tissue a site of concentration for protein. In light consistent research showing some associations between context obesity, metabolic disorders, diabetes, this review tunes possible role pathogenic processes these which are known to involve tissue. reported data suggest obesity/diabetes processes, thus putatively re-proposing played by astrocytic neuroinflammatory/neurodegenerative processes.

Language: Английский

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The case for precision medicine in the prevention, diagnosis, and treatment of cardiometabolic diseases in low-income and middle-income countries

The Lancet Diabetes & Endocrinology, Journal Year: 2023, Volume and Issue: 11(11), P. 836 - 847

Published: Oct. 4, 2023

Language: Английский

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Single‐Administration Self‐Boosting Microneedle Patch for the Treatment of Obesity

Advanced Therapeutics, Journal Year: 2024, Volume and Issue: unknown

Published: May 21, 2024

Abstract Glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) are one of the most effective treatments for obesity. The current therapy associated with repeated subcutaneous injections to maintain drug therapeutic effect causes patient compliance issues and raises environmental concerns (due sharp biohazard waste from disposed syringes/needles). Herein, a programmable scheduled release microneedles (PSR‐MNs) system is reported delivering Semaglutide (a GLP‐1 RA agent half‐life ≈7 days) manage treat A single skin administration PSR‐MNs patch (2 cm × 2 cm) that contains 4 core‐shell microneedle (MNs) patches (1 each, so‐called pixels) enables every 7 days sustains efficacy an unprecedented one‐month period, simulating using four bolus spaced apart. This provides advanced injection‐free platform significantly enhance treatment obesity GLP‐1RAs, addressing related pain, needle phobia, high cost, need medical facilities/personnel in traditional administer drug.

Language: Английский

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The enduring metabolic improvement of combining dual amylin and calcitonin receptor agonist and semaglutide treatments in a rat model of obesity and diabetes

AJP Endocrinology and Metabolism, Journal Year: 2024, Volume and Issue: 327(2), P. E145 - E154

Published: June 12, 2024

These studies describe the benefit of combining dual amylin and calcitonin receptor agonists (DACRA) with semaglutide for long-term treatment obesity type 2 diabetes. Combination induced sustained weight loss improved glucose control. A DACRA-driven reduction in a serological biomarker cardiac fibrosis indicated reduced risk complications. results highlight DACRAs as promising candidate combination diabetes related

Language: Английский

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Associations of Serum Lipid Traits With Fracture and Osteoporosis: A Prospective Cohort Study From the UK Biobank

Journal of Cachexia Sarcopenia and Muscle, Journal Year: 2024, Volume and Issue: 15(6), P. 2669 - 2683

Published: Oct. 29, 2024

ABSTRACT Background Previous studies reveal inconsistent associations between serum lipid traits and the risks of fractures osteoporosis in general population. Methods This prospective cohort study analysed data from 414 302 UK Biobank participants (223 060 women 191 242 men, aged 37–73 years) with measurements: apolipoprotein A (Apo A), B B), total cholesterol (TC), high‐density lipoprotein (HDL‐C), low‐density (LDL‐C), triglycerides (TG) (Lp(a)). Multivariable Cox proportional hazard models penalized cubic splines were used to explore potential nonlinear each trait osteoporosis. Subgroup analyses by age, sex, BMI categories pre‐existing cardiovascular disease conducted. Mediation using g‐formula performed quantify which extent bone mineral density (BMD) may mediate association lipids fracture risk. Results Over a median follow‐up period 13.8 years, 25 918 (6.8%) 383 530 without prior had incident cases, 7591 (4.1%) 184 919 primary care baseline diagnosed TG osteoporosis, whereas Apo B, TC LDL‐C linear associations. There also HDL‐C fractures. Individuals highest quintiles for (fracture: HR 1.15 [95% CI 1.10, 1.21]; osteoporosis: 1.13 [1.02, 1.25]) 1.27 [1.20, 1.34]; 1.31 [1.18, 1.46]) associated higher Conversely, those quintile 0.85 [0.81, 0.89]; 0.86 [0.79, 0.94]), 0.89 [0.85, 0.93]; 0.91 [0.83, 1.00]) 0.78 [0.74, 0.82]; 0.75 [0.68, 0.82]) lower risks. The (ratio [RHR] 1.05 1.09]) (RHR 1.06 [1.03, risk more pronounced men compared women. Except Lp(a), appear be partially mediated through BMD (mediation proportions: 5.30% 40.30%), assuming causality. Conclusions Our reveals complex interplay different markers skeletal health, potentially BMD. Routine profile assessments, including among other traits, integrated into strategies stratification.

Language: Английский

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Feruloylacetone and Its Analog Demethoxyferuloylacetone Mitigate Obesity-Related Muscle Atrophy and Insulin Resistance in Mice

Journal of Agricultural and Food Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 4, 2025

Obesity-induced muscle alterations, such as inflammation, metabolic dysregulation, and myosteatosis, lead to a decline in mass function, often resulting sarcopenic obesity. Currently, there are no definitive treatments for obesity beyond lifestyle changes dietary supplementation. Feruloylacetone (FER), thermal degradation product of curcumin, its analog demethoxyferuloylacetone (DFER), derived from the bisdemethoxycurcumin, have shown potential antiobesity effects previous studies. This study investigates impact FER DFER on obesity-related glucose intolerance atrophy. High-fat diet (HFD) feeding resulted reduction increased intramuscular triglyceride accumulation, both which were mitigated by The supplements activated PI3K/Akt/mTOR signaling pathway, enhanced protein synthesis, decreased markers degradation. Additionally, supplementation improved homeostasis HFD-fed mice. also promoted formation gut microbial consortium comprising Blautia intestinalis, Dubosiella newyorkensis, Faecalicatena fissicatena, Waltera Clostridium viride, Caproiciproducens galactitolivorans, contributed obesity-induced chronic inflammation. These findings suggest, first time, that may prevent complications, including atrophy insulin resistance, thereby warranting further research into their long-term efficacy safety.

Language: Английский

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A novel human specific lncRNA MEK6-AS1 regulates adipogenesis and fatty acid biosynthesis by stabilizing MEK6 mRNA

Journal of Biomedical Science, Journal Year: 2025, Volume and Issue: 32(1)

Published: Jan. 8, 2025

Abstract Background Obesity is becoming one of the major non-communicable diseases with increasing incidence and risks that cannot be ignored. However effective safe clinical treatment strategies still need to deeply explored. Increased number volume adipocytes lead overweight obesity. The aim our work identify lncRNAs have important regulatory in differentiation human mesenchymal stem cells (MSCs) into adipocytes, provide targets for prevention obesity related metabolic disorders. Methods We extracted primary MSCs from adipose tissue, conducted expression profile analysis during adipogenic screen changed lncRNAs. Characteristics lncRNA were revealed mainly by RACE RNA FISH. Loss- gain-of function experiments vivo vitro used analyze effects lncRNA. Targeted metabolomics was utilized detect levels free fatty acids. pull-down, mRNA stability tests, etc. employed explore mechanisms Results Human-specific lncRNA, we named it MEK6-AS1, most up-regulated transcript MSCs. MEK6-AS1 highly expressed tissue samples individuals BMI ≥ 25 positively correlated marker genes these samples. Knocking down inhibited markers ectopic adipogenesis, reducing contents various acids, as well promoting osteogenic differentiation. Overexpression had opposite above processes. also found elevated hepatic steatosis organoid generation. Mechanistically, worked partially through stabilization MEK6 NAT10. Conclusions identified a human-specific (MEK6-AS1) position information genomic database but has not been extensively reported. demonstrated novel involved acid metabolism, may exert its effect enhancing Our study insights implication cell biology offer new potential therapeutic target other disease.

Language: Английский

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Use of Semaglutide (Wegovy) in Adults in France: A Nationwide Drug Utilization Study

BioDrugs, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 11, 2025

Language: Английский

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Individual participant data meta-analysis of eating behaviour traits as effect modifiers in acceptance and commitment therapy-based weight management interventions

International Journal of Obesity, Journal Year: 2025, Volume and Issue: unknown

Published: April 10, 2025

Abstract Background Obesity care may benefit from precision approaches, matching patients to treatment types based on their individual characteristics, including eating behaviour traits (EBTs) like emotional eating, uncontrolled external internal disinhibition and restraint. Initial evidence suggests that Acceptance Commitment Therapy (ACT)-based interventions might address dysregulated EBTs more effectively than standard behavioural treatments. However, it is unclear if ACT effective for certain EBT levels. Methods analysis This pre-registered (CRD42022359691) one-stage Individual Participant Data (IPD) meta-analysis explored the moderating effects of baseline weight outcomes in trials ACT-based adults with a BMI ≥ 25 kg/m 2 . Unlike traditional meta-analyses, IPD meta-analyses re-analyse existing data answer novel research questions. We identified 16 eligible through systematic search eight databases until June 20, 2022. obtained, checked, harmonised 15 ( N = 2535). used mixed regression models investigate both continuous categorical interaction effects. Results found no interactions between vs. control as variables percentage change. we suggest an added difference change −4.47% (95%CI −1.15, −7.73) 12-months after intervention end participants medium levels compared those high Sensitivity analyses similarly indicated greater medium, rather high, (in reduced experiential avoidance using three-factor questionnaire) at least 60% attendance). Given exploratory nature analyses, results should be interpreted caution. Conclusion Findings potential non-linear but require replication confirmatory trials. These help guide further approaches EBTs.

Language: Английский

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