RESUMEN
BACKGROUND: Dyslipidemia is a common complication in patients with diabetes mellitus (DM) that increases the risk of cardiovascular disease. Genetic polymorphisms have been implicated in the development of dyslipidemia. AIM: To investigate the association between polymorphisms of candidate genes involved in lipid metabolism and dyslipidemia in Chinese patients with DM. METHODS: A cross-sectional study was conducted on 1098 Chinese patients with DM recruited from multiple healthcare centers. Demographic and clinical data were collected, and dyslipidemia was defined according to the National Cholesterol Education Program Adult Treatment Panel III guidelines. Genomic DNA was extracted from blood samples and genotyping for selected polymorphisms of candidate genes (APOE, LPL, CETP, and others) was performed using PCR and DNA sequencing techniques. Statistical analyses were performed using logistic regression models adjusted for potential confounding factors. RESULTS: The study population consisted of 578 males (52.6%) and 520 females (47.4%), with a mean age of 58.4 ± 12.2 years. The prevalence of dyslipidemia was 64.8%. Significant associations were found between dyslipidemia and the APOE rs7412 T/T, APOE rs429358 C/C, LPL rs328 G/G, and CETP rs708272 G/G genotypes after adjusting for covariates. Subgroup analyses showed generally consistent associations across subgroups, although some variations in effect sizes were observed. CONCLUSION: This study identified significant associations between genetic polymorphisms of APOE, LPL, and CETP genes and dyslipidemia in Chinese patients with DM.
RESUMEN
Cardiac fibrosis is a typical feature of cardiac pathological remodeling, which is associated with adverse clinical outcomes and has no effective therapy. Nicotine is an important risk factor for cardiac fibrosis, yet its underlying molecular mechanism remains poorly understood. This study aimed to identify its potential molecular mechanism in nicotine-induced cardiac fibrosis. Our results showed nicotine exposure led to the proliferation and transformation of cardiac fibroblasts (CFs) into myofibroblasts (MFs) by impairing autophagy flux. Through the use of drug affinity responsive target stability (DARTS) assay, cellular thermal shift assay (CETSA), and surface plasmon resonance (SPR) technology, it was discovered that nicotine directly increased the stability and protein levels of lactate dehydrogenase A (LDHA) by binding to it. Nicotine treatment impaired autophagy flux by regulating the AMPK/mTOR signaling pathway, impeding the nuclear translocation of transcription factor EB (TFEB), and reducing the activity of cathepsin B (CTSB). In vivo, nicotine treatment exacerbated cardiac fibrosis induced in spontaneously hypertensive rats (SHR) and worsened cardiac function. Interestingly, the absence of LDHA reversed these effects both in vitro and in vivo. Our study identified LDHA as a novel nicotine-binding protein that plays a crucial role in mediating cardiac fibrosis by blocking autophagy flux. The findings suggest that LDHA could potentially serve as a promising target for the treatment of cardiac fibrosis.
Asunto(s)
Autofagia , Fibrosis , Nicotina , Animales , Autofagia/efectos de los fármacos , Ratas , Masculino , Ratas Endogámicas SHR , Transducción de Señal/efectos de los fármacos , Miocardio/patología , Miocardio/metabolismo , Lactato Deshidrogenasa 5/metabolismo , Células Cultivadas , Humanos , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Miofibroblastos/efectos de los fármacos , Miofibroblastos/metabolismo , Ratas Sprague-DawleyRESUMEN
Spasmodic torticollis (ST) is a focal dystonia that affects adults, causing limited muscle control and impacting daily activities and quality of life. The etiology and curative methods for ST remain unclear. Botulinum toxin is widely used as a first-line treatment, but long-term usage can result in reduced tolerance and adverse effects. Rehabilitation therapy, with its minimal side effects and low potential for harm, holds significant clinical value. This article explores the effectiveness of adjunctive therapies, including exercise therapy, transcranial magnetic stimulation, shockwave therapy, neuromuscular electrical stimulation, vibration therapy, electromyographic biofeedback, and acupuncture, in the treatment of ST. The aim is to provide clinicians with additional treatment options and to discuss the efficacy of rehabilitation therapy for ST.