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Purpose: Migraine is a complex neurovascular disorder with obesity as a notable risk factor. This study aimed to investigate an under-researched area of the association between migraine duration and body composition. Patients and Methods: Patients with migraine from a neurology outpatient department were enrolled and were categorized into four groups based on illness duration: 1 year, 1-5 years, 5-10 years, and >10 years. Patient demographics, blood biochemistry, and body composition data were collected and analyzed statistically. Results: Patients with migraine were predominantly female, with lower education levels, significant work stress, poor sleep, and limited exercise. Longer migraine duration corresponded to increased obesity metrics. Notably, those patients with under 1 year of illness showed elevated blood lipid and liver function levels, whereas those with >10 years showed increased weight, waist circumference, body mass index, and fat content, despite higher physical activity. Significant positive correlation between obesity metrics and migraine duration was seen in patients who had migraine for >1 year. Conclusion: Our findings indicate that protracted episodes of migraine could amplify obesity tendencies, underscoring the imperative of weight regulation in migraine intervention to diminish ensuing adiposity-associated hazards.
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PURPOSE: Migraine, a severely debilitating condition, may be effectively managed with topiramate, known for its migraine prevention and weight loss properties due to changes in body muscle and fat composition and improved insulin sensitivity. However, the mechanism of topiramate in modulating insulin response in adipocytes and myocytes remains elusive. This study aims to elucidate these molecular mechanisms, offering insights into its role in weight management for migraine sufferers and underpinning its clinical application. METHODS: Insulin resistance improvements were evaluated through glucose uptake measurements in C2C12 muscle cells and 3T3L-1 adipocytes, with Oil red O staining conducted on adipocytes. RNA-seq transcriptome analysis was used to identify the regulatory target genes of topiramate in these cells. The involvement of key genes and pathways was further validated through western blot analysis. RESULTS: Topiramate effectively reduced insulin resistance in C2C12 and 3T3L-1 cells. In C2C12 cells, it significantly lowered SORBS1 gene and protein levels. In 3T3L-1 cells, topiramate upregulated CTGF and downregulated MAPK8 and KPNA1 genes. Changes were notable in nuclear cytoplasmic transport and circadian signaling pathways. Furthermore, it caused downregulation of MKK7, pJNK1/ JNK1, BMAL1, and CLOCK proteins compared to the insulin-resistant model. CONCLUSION: This study provides preliminary insights into the mechanisms through which topiramate modulates insulin resistance in C2C12 myocytes and 3T3L-1 adipocytes, enhancing our understanding of its therapeutic potential in managing weight and insulin sensitivity in migraine patients.
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Adipocitos , Resistencia a la Insulina , Topiramato , Animales , Topiramato/farmacología , Topiramato/uso terapéutico , Resistencia a la Insulina/fisiología , Ratones , Adipocitos/efectos de los fármacos , Adipocitos/metabolismo , Células Musculares/efectos de los fármacos , Células Musculares/metabolismo , Línea Celular , Células 3T3-L1 , Transducción de Señal/efectos de los fármacosRESUMEN
AIMS: To explore the effectiveness of the Taiwanese Diabetes Shared Care Program (DSCP) on improving the metabolic indicators of people with type 2 diabetes. METHODS: Relevant studies published between January 2002 and August 2021 were retrieved from Chinese- and English-language electronic databases, including PubMed, MEDLINE, CINAHL, ProQuest, Cochrane Library, Airiti Library, and Taiwan Periodical Literature System. After screening, studies that met inclusion criteria were included in the literature review. RevMan 5.4 was employed for a meta-analysis. RESULTS: Ten studies published between 2007 and 2021 were included in the systematic review, with nine of them contributing to the meta-analysis. In total, 1506 and 1388 participants were classified into DSCP and non-DSCP groups, respectively, for the meta-analysis. The results revealed that the DSCP significantly improved glycated hemoglobin levels (mean difference [MD]: -0.50, 95% Confidence Interval [CI]: -0.83 to -0.17) and body weights (MD: -0.83, 95% CI: -1.29 to -0.38) within 1-year follow-up. However, it did not show significant improvement in other metabolic indicators. CONCLUSIONS: Taiwanese DSCP led to improvements in glycated hemoglobin levels and body weights among people with type 2 diabetes. This study suggests that people with diabetes and health-care institutions should consider participating in the DSCP.
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Biomarcadores , Prestación Integrada de Atención de Salud , Diabetes Mellitus Tipo 2 , Hemoglobina Glucada , Control Glucémico , Diabetes Mellitus Tipo 2/terapia , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/epidemiología , Humanos , Hemoglobina Glucada/metabolismo , Biomarcadores/sangre , Persona de Mediana Edad , Femenino , Masculino , Resultado del Tratamiento , Glucemia/metabolismo , Anciano , Taiwán/epidemiología , Evaluación de Programas y Proyectos de Salud , Adulto , Factores de Tiempo , Hipoglucemiantes/uso terapéutico , Peso CorporalRESUMEN
The forkhead box protein P2 (Foxp2), initially identified for its role in speech and language development, plays an important role in neural development. Previous studies investigated the function of the Foxp2 gene by deleting or mutating Foxp2 from developmental stages. Little is known about its physiological function in adult brains. Although Foxp2 has been well studied in the dorsal striatum, its function in the nucleus accumbens (NAc) of the ventral striatum remains elusive. Here, we examine the physiological function of Foxp2 in NAc of mouse brains. We conditionally knocked out Foxp2 by microinjections of AAV-EGFP-Cre viruses into the medial shell of NAc of Foxp2 floxed (cKO) mice. Immunostaining showed increased c-Fos positive cells in cKO NAc at basal levels, suggesting an abnormality in Foxp2-deficient NAc cells. Unbiased behavioral profiling of Foxp2 cKO mice showed abnormalities in limbic-associated function. Foxp2 cKO mice exhibited abnormal social novelty without preference for interaction with strangers and familiar mice. In appetitive reward learning, Foxp2 cKO mice failed to learn the time expectancy of food delivery. In fear learning, Foxp2 cKO mice exhibited abnormal increases in freezing levels in response to tone paired with foot shock during fear conditioning. The extinction of the fear response was also altered in Foxp2 cKO mice. In contrast, conditional knockout of Foxp2 in NAc did not affect locomotion, motor coordination, thermal pain sensation, anxiety- and depression-like behaviors. Collectively, our study suggests that Foxp2 has a multifaceted physiological role in NAc in the regulation of limbic function in the adult brain.
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Aprendizaje , Núcleo Accumbens , Ratones , Animales , Núcleo Accumbens/metabolismo , Factores de Transcripción Forkhead/genética , Factores de Transcripción Forkhead/metabolismo , Proteínas Represoras/metabolismoRESUMEN
Background: Elevated Phospholipids (PLs) and sphingolipid (SM) metabolism relates to with poor clinical status and adverse outcome of end-stage kidney disease patients undergoing peritoneal dialysis (PD). Studies have suggested that the use of hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) (Roxadustat) is associated with altered lipid metabolism. Observing on how PLs and SMs changes after the HIF-PHI treatment in PD patients may help understand the possible effect of HIF-PHI on PD patients besides correcting of anemia. Materials and methods: Stable peritoneal dialysis (PD) patients treated with Roxadustat for over 3 months were included. Phospholipid and sphingolipid metabolism were measured before and after treatment. Results: 25 PD patients were included. Overall, phospholipid and sphingolipid metabolism showed a decreasing trend after HIF-PHI treatment. Levels of LysoPC (20:0), 1,2-dilinoleoyl-sn-glycero-3-phosphocholine [CisPC (DLPC) (18:2)], lysophosphatidylethanolamine (LysoPE) (14:0), and sphingomyelin (d18:1/17:0) (17:0) were significantly decreased (all p < 0.05). Further regression analyses confirmed the significant relationship between the increased of hemoglobin levels and the decrease in egg lyso PC: phosphatidylethanolamines (PE) (16:0-18:1), PE (16:0-18:2), PE (16:0-22:6), PE (18:0-20:4), PE (18:0-18:2), LysoPE (18:0), LysoPE (18:1), and phosphatidylcholine (PC) (18:1-18:0). Conclusion: This study demonstrated that phospholipid and sphingolipid metabolism decreased after administration of HIF-PHI and was associated with improvement of anemia.