ABSTRACT The pharmacological activation of peroxisome proliferator‐activated receptor gamma (PPARγ) is a convenient and promising strategy for promoting beige adipocyte biogenesis to combat obesity‐related metabolic disorders. However, thiazolidinediones (TZDs), the full agonists of PPARγ exhibit severe side effects in animal models and in clinical settings. Therefore, the development of efficient and safe PPARγ modulators for the treatment of metabolic diseases is emerging. In this study, using comprehensive methods, we report a previously unidentified ligand‐binding pocket (LBP) in PPARγ and link it to beige adipocyte differentiation. Further virtual screening of 4097 natural compounds based on this novel LBP revealed that saikosaponin A (NJT‐2), a terpenoid compound, can bind to PPARγ to induce coactivator recruitment and effectively activate PPARγ‐mediated transcription of the beige adipocyte program. In a mouse model, NJT‐2 administration efficiently promoted beige adipocyte biogenesis and improved obesity‐associated metabolic dysfunction, with significantly fewer adverse effects than those observed with TZD. Our results not only provide an advanced molecular insight into the structural ligand‐binding details in PPARγ, but also develop a linked selective and safe agonist for obesity treatment.
Introduction: Radiation induced meningiomas (RIM) occur in patients with prior history of radiation to the craniospinal axis or head and neck region, for the treatment of prior malignancies. These tumors tend to follow a more aggressive natural history with a tendency for progression and recurrence.
Background WHO Grade II meningiomas account for 10 to 15% of all meningiomas. These tumors have a 5-year recurrence rates between 30 and 50%, and 5-year survival rates as low as 50%. Surgery is the primary treatment for these neoplasms, while the use of various adjuvant treatments remains debated. Continuing to study patient outcomes in relation to histological features, and clinical course, will help clinicians and surgeons makes informed, evidence-based treatment plans to optimize care for patients with WHO Grade II meningiomas.
Introduction The rising incidence of heart failure (HF) among the U.S. population has become a major concern for healthcare providers. This study aims to assess mortality trends related to HF across different age groups, racial demographics, and geographic locations from 1999 to 2020. Material and methods This descriptive analysis uses death certificate data from the CDC WONDER database to track mortality trends among HF patients from 1999 to 2020. Log-linear regression models were used to delineate trends. The study used deidentified public data, complying with ethical standards. Results Over 21 years, 1,426,657 HF-related deaths were recorded in individuals aged 15 and older, with a slight overall increase in mortality (AAPC = 0.11). Mississippi recorded the highest age-adjusted mortality rates (AAMRs) at 58.0 per 100,000. The Midwest showed the highest regional mortality rates, while the oldest individuals (≥ 85) exhibited the highest crude mortality rate (CMR) of 663.9. Males consistently demonstrated higher AAMRs than females, despite females accounting for 57.6% of the deaths. Black ancestry individuals experienced the highest mortality rates, with rising trends, particularly in non-metropolitan areas. After 2012, significant increases in mortality were noted, especially in individuals over 85, with stable rates in younger demographics. Conclusions Males and Black ancestry individuals are disproportionately affected, demonstrating the need for targeted interventions.
Aortic dissection (AD) is a potentially fatal cardiovascular issue that needs to be diagnosed and treated very away. While early detection is essential for bettering patient outcomes, there are substantial obstacles with the diagnostic techniques used today. Promising pathways for improving AD prognosis evaluation and early detection are presented by recent developments in serum biomarkers. The most recent research on serum biomarkers for AD is reviewed here, with an emphasis on the prognostic and diagnostic utility of these indicators. A number of biomarkers, including as matrix metalloproteinases, soluble elastin fragments, smooth muscle myosin heavy chain, and D-dimer, have been identified as putative markers of AD. These indicators are indicative of multiple pathophysiological mechanisms associated with AD, including inflammation, extracellular matrix remodeling, and vascular damage. Research has indicated that they are useful in differentiating AD from other acute cardiovascular diseases, facilitating prompt diagnosis and risk assessment.
Non-alcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) is the most common chronic liver disease in the world. However, there are still no drugs for NAFLD/NASH in the market. Gastrodin (GAS) is a bioactive compound that is extracted from
Cerebral infections have been reported after endovascular interventions such as embolization and coiling. Such complications are extremely rare and only one other case has been reported in a patient who underwent an endovascular therapy for ischemic stroke. We report a 32-year-old woman, who presented to our hospital with headaches lasting four weeks after an endovascular intervention for ischemic stroke via mechanical thrombectomy. Further investigations revealed a cerebral abscess in the area of the infarct. She was effectively treated with antibiotics in combination with stereotactic drainage and was discharged after she made a good recovery. A review of literature on cerebral abscesses after minimally invasive procedures such as endovascular intervention was also done and is being presented in this paper. A cerebral abscess can occur rarely after endovascular interventions. A high degree of suspicion is important in identifying patients with an abscess and appropriate treatment can prevent significant morbidity or even death.
Nonalcoholic fatty liver disease (NAFLD)1 is the most common chronic liver disease worldwide. Cichorium glandulosum Boiss. et Huet (CG) is a common traditional Uighur medicine, and it has been widely used as active therapy on various hepatic diseases. Recently, lipid-lowering effect has been revealed on CG. Polysaccharides are principal component of CG which could be the possible lipid-lowering compound in CG. In this study, extraction and purification of CG polysaccharides (CGP) was performed, and the lipid regulation effect of CGP was investigated on NAFLD zebrafish model. The results showed that CGP significantly decreased the levels of TC, TG, and decreased the mRNA expression of srebf-1, and fas, increased the expression of pparab. The findings suggest that the lipid-lowering effects of CGP mainly depend on facilitation of lipolysis (mainly beta-oxidation) or inhibition of lipogenesis. Furthermore, CGP could prevent and causes the regression of steatosis in NAFLD via its lipid metabolism regulation effect.
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease around the world.However, there is still no drug for NAFLD in the market, the study of potential therapeutic drugs on NAFLD is extraordinarily pressing and urgent.The rodent models for NAFLD drugs' study are always with a long time cost.Therefore, we aim to establish a short-time NAFLD drug screening model.A laboratory-made high cholesterol diet was used on larval zebrafish for 3 weeks to establish the NAFLD screen model.Lipid metabolism, oxidant stress, and pathology were studied to comprehensively demonstrate the whole spectrum of NAFLD on this model.Bezafibrate and pioglitazone were used to evaluate the model.Moreover, mechanism research was performed on this model.The NAFLD larval zebrafish model was established with the comprehensive process of NAFLD.Moreover, multiple index on lipid metabolism, oxidant stress, hepatic steatosis, and hepatic inflammation can be easily tested for drug screening.Furthermore, this model can be used to perform the mechanism research by testing mRNA expression.The NAFLD larval zebrafish model is a comprehensive short-time screening method for NAFLD drugs.
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