RESUMEN
Aim: The aim of this research was to ascertain the correlations between alexithymia, social support, depression, and glycemic control in patients diagnosed with type 2 diabetes mellitus. Additionally, this study sought to delve into the potential mediating effects of social support and depression in the relationship between alexithymia and glycemic control. Method: A purposive sampling methodology was employed to select a cohort of 318 patients afflicted with type 2 diabetes mellitus, hailing from a care establishment situated in Chengdu City. This investigation embraced a cross-sectional framework, wherein instruments such as the General Information Questionnaire, the Toronto Alexithymia Scale 20, the Social Support Rating Scale, and the Hamilton Depression Scale were judiciously administered. The primary objective of this endeavor was to unravel the interplay that exists amongst alexithymia, social support, depression, and glycemic control. The inquiry discerned these interrelationships through both univariate and correlational analyses, subsequently delving into a comprehensive exploration of the mediating ramifications engendered by social support and depression in the nexus between alexithymia and glycemic control. Results: The HbA1c level of patients diagnosed with type 2 diabetes mellitus was recorded as (8.85 ± 2.107), and their current status with regards to alexithymia, social support, and depression were measured as (58.05 ± 4.382), (34.29 ± 4.420), and (7.17 ± 3.367), respectively. Significant correlations were found between HbA1c and alexithymia (R=0.392, P<0.01), social support (R=-0.338, P<0.01), and depression (R=0.509, P<0.01). Moreover, alexithymia correlation with social support (R=-0.357, P<0.01) and with depression (R=0.345, P<0.01). Regarding the mediation analysis, the direct effect of alexithymia on HbA1c was calculated to be 0.158, while the indirect effect through social support and depression were 0.086 and 0.149, respectively. The total effect value was determined to be 0.382, with the mediating effect accounting for 59.95%, and the direct effect accounting for 40.31%. Conclusion: Alexithymia exerts both direct and indirect adverse effects on glycemic control, thereby exacerbating disease outcomes. Hence, it is imperative to prioritize the mental health status of individuals with type 2 diabetes to enhance overall well-being, ameliorate diabetes-related outcomes, elevate patients' quality of life, and alleviate the psychological distress and financial burden associated with the condition.
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Síntomas Afectivos , Depresión , Diabetes Mellitus Tipo 2 , Control Glucémico , Apoyo Social , Humanos , Diabetes Mellitus Tipo 2/psicología , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Síntomas Afectivos/epidemiología , Femenino , Masculino , Persona de Mediana Edad , Depresión/epidemiología , Depresión/psicología , Estudios Transversales , Control Glucémico/psicología , Análisis de Clases Latentes , Adulto , Anciano , Hemoglobina Glucada/análisis , Hemoglobina Glucada/metabolismo , Glucemia/análisis , Glucemia/metabolismoRESUMEN
Introduction: Research has demonstrated that higher social support is associated with better psychological health, quality of life, cognition, activities of daily living, and social participation, but the relationship between social support and sleep quality remains unknown. This study aims to investigate the mediating effects of anxiety and depression in the relationship between social support and sleep among community-dwelling patients with schizophrenia. Method: Purposive sampling was used to collect face-to-face data from 1,107 community-dwelling patients with schizophrenia in Chengdu, Sichuan Province, China, between April and July 2023. The Athens Insomnia Scale (AIS) was used to assess sleep quality; the Generalized Anxiety Disorder 7-item scale (GAD-7) was utilized to evaluate anxiety symptoms; and the Patient Health Questionnaire-9 (PHQ-9) was employed to assess depressive symptoms. The mediating effect of anxiety and depression symptoms was assessed using the bootstrap method via Model 6 (Serial multiple mediator model) of the SPSS PROCESS macro. Results: Among the 1,107 participants, the proportions of people with schizophrenia experiencing anxiety, depressive symptoms, and poor sleep quality were 22.8, 37.7, and 42.1%, respectively. Mediation analyses indicated that although social support had no direct effect on sleep quality, anxiety and depressive symptoms fully mediated the relationship between social support and sleep quality. Conclusion: Patients with schizophrenia experience low levels of social support and poor sleep quality. To enhance the sleep quality of individuals with schizophrenia, all levels of society (government, medical institutions, and communities) must pay more attention to mental health. Implementing diverse intervention measures to strengthen social support and improve symptoms of anxiety and depression should be considered. This approach may potentially lead to an improvement in sleep quality among individuals with schizophrenia.
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Ansiedad , Depresión , Esquizofrenia , Calidad del Sueño , Apoyo Social , Humanos , Masculino , Femenino , Esquizofrenia/complicaciones , Adulto , China/epidemiología , Depresión/epidemiología , Persona de Mediana Edad , Encuestas y Cuestionarios , Calidad de Vida/psicología , Vida IndependienteRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Xanthium sibiricum Patrin ex Widder (X. sibiricum) are widely used traditional herbal medicines for arthritis treatment in China. Rheumatoid arthritis (RA) is characterized by progressive destructions of joints, which is accompanied by chronic, progressive inflammatory disorder. According to our previous research, tomentosin was isolated from X. sibiricum and revealed anti-inflammatory activity. However, the potential therapeutic effect of tomentosin on RA and the anti-inflammatory mechanism of tomentosin remain to be clarified. The present study lays theoretical support for X. sibiricum in RA treatment, also provides reference for further development of X. sibiricum in clinic. AIM OF THE STUDY: To investigate the effect of tomentosin in collagen-induced arthritis (CIA) mice and reveal its underlying mechanism. MATERIALS AND METHODS: In vivo, tomentosin (10, 20 and 40 mg/kg) was given to CIA mice for seven consecutive days, to evaluate its therapeutic effect and anti-inflammatory activity. In vitro, THP-1-derived macrophages were used to verify the effect of tomentosin on inflammation. Then, molecular docking and experiments in vitro was conducted to predict and explore the mechanism of tomentosin inhibiting inflammation. RESULTS: Tomentosin attenuated the severity of arthritis in CIA mice, which was evidenced by the swelling of the hind paws, arthritis scores, and pathological changes. Particularly, tomentosin effectively reduced the ratio of M1 macrophage and TNF-α levels in vitro and vivo. Then, molecular docking and experiments in vitro was carried out, indicating that tomentosin inhibited M1 polarization and TNF-α levels accompanied by the increase of MERTK and up-regulated GAS6 levels. Moreover, it has been proved that GAS6 was necessary for MERTK activation and tomentosin could up-regulate GAS6 levels effectively in transwell system. Further mechanistic studies revealed that tomentosin suppressed M1 polarization via increasing MERTK activation mediated by regulation of GAS6 in transwell system. CONCLUSION: Tomentosin relieved the severity of CIA mice by inhibiting M1 polarization. Furthermore, tomentosin suppressed M1 polarization via increasing MERTK activation mediated by regulation of GAS6.
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Artritis Experimental , Artritis Reumatoide , Ratones , Animales , Tirosina Quinasa c-Mer , Factor de Necrosis Tumoral alfa , Simulación del Acoplamiento Molecular , Inflamación/tratamiento farmacológico , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Artritis Experimental/inducido químicamente , Artritis Experimental/tratamiento farmacológico , Artritis Experimental/patologíaRESUMEN
CONTEXT: Rheumatoid arthritis (RA) is an autoimmune disease with aberrant Th17 cell differentiation. Panax notoginseng (Burk.) F. H. Chen (Araliaceae) saponins (PNS) have an anti-inflammatory effect and can suppress Th17 cell differentiation. OBJECTIVE: To investigate mechanisms of PNS on Th17 cell differentiation in RA, and the role of pyruvate kinase M2 (PKM2). MATERIALS AND METHODS: Naive CD4+T cells were treated with IL-6, IL-23 and TGF-ß to induce Th17 cell differentiation. Apart from the Control group, other cells were treated with PNS (5, 10, 20 µg/mL). After the treatment, Th17 cell differentiation, PKM2 expression, and STAT3 phosphorylation were measured via flow cytometry, western blots, or immunofluorescence. PKM2-specific allosteric activator (Tepp-46, 50, 100, 150 µM) and inhibitor (SAICAR, 2, 4, 8 µM) were used to verify the mechanisms. A CIA mouse model was established and divided into control, model, and PNS (100 mg/kg) groups to assess an anti-arthritis effect, Th17 cell differentiation, and PKM2/STAT3 expression. RESULTS: PKM2 expression, dimerization, and nuclear accumulation were upregulated upon Th17 cell differentiation. PNS inhibited the Th17 cells, RORγt expression, IL-17A levels, PKM2 dimerization, and nuclear accumulation and Y705-STAT3 phosphorylation in Th17 cells. Using Tepp-46 (100 µM) and SAICAR (4 µM), we demonstrated that PNS (10 µg/mL) inhibited STAT3 phosphorylation and Th17 cell differentiation by suppressing nuclear PKM2 accumulation. In CIA mice, PNS attenuated CIA symptoms, reduced the number of splenic Th17 cells and nuclear PKM2/STAT3 signaling. DISCUSSION AND CONCLUSIONS: PNS inhibited Th17 cell differentiation through the inhibition of nuclear PKM2-mediated STAT3 phosphorylation. PNS may be useful for treating RA.
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Panax notoginseng , Saponinas , Ratones , Animales , Saponinas/farmacología , Células Th17 , Fosforilación , Diferenciación CelularRESUMEN
CONTEXT: Rheumatoid arthritis (RA) is an autoimmune disease with the aberrant differentiation of T helper 17 (Th17) cells. Pyruvate kinase M2 (PKM2), a key enzyme of glycolysis, was associated with Th17 cell differentiation. AIM: To investigate the potential therapeutic effects of triptolide (TP) in collagen-induced arthritis (CIA) and Th17 cell differentiation, and elucidated the underlying mechanisms. METHODS: PKM2 expression and IL-17A production in peripheral blood of RA patients were detected by RT-qPCR or ELISA. Flow cytometry and ELISA were employed to assess the effect of Th17 cell differentiation by TP. PKM2 expression and other glycolysis-related factors were detected using RT-qPCR and Western Blot. PKM2 specific inhibitor Compound 3 K was used to verify the mechanisms. Male DBA/1J mice were divided into control, model, and TP (60 µg/kg) groups to assess the anti-arthritis effect, Th17 cell differentiation and PKM2 expression. RESULTS: PKM2 expression positively correlated with IL-17A production in RA patients. PKM2 expression was increased upon Th17 cell differentiation. Down-regulating PKM2 expression could strongly reduce Th17 cell differentiation. Molecular docking analysis predicted that TP targeted PKM2. TP treatment significantly reduced Th17 cell differentiation, PKM2 expression, pyruvate, and lactate production. In addition, compared with down-regulating PKM2 alone (Compound 3 K treatment), co-treatment with TP and Compound 3 K further significantly decreased PKM2-mediated glycolysis and Th17 cell differentiation. In CIA mice, TP repressed the PKM2-mediated glycolysis and attenuated joint inflammation. CONCLUSION: TP inhibited Th17 cell differentiation through the inhibition of PKM2-mediated glycolysis. We highlight a novel strategy for the use of TP in RA treatment.
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Artritis Reumatoide , Interleucina-17 , Masculino , Animales , Ratones , Ratones Endogámicos DBA , Simulación del Acoplamiento Molecular , Artritis Reumatoide/tratamiento farmacológico , Diferenciación CelularRESUMEN
PURPOSE: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease, and Th17 cells are key factors in the pathogenesis of human inflammatory conditions, such as RA. Catalpol (CAT), a component in Rehmanniae Radix (RR), has been found to regulate human immunity. However, the effects of CAT on Th17 cell differentiation and improvement of RA are not clear. MATERIALS AND METHODS: Collagen-induced arthritis (CIA) mice were constructed to detect the effects of CAT on arthritis and Th17 cells. The effect of CAT on Th17 differentiation was evaluated with let-7g-5p transfection experiments. Flow cytometry was used to detect the proportion of Th17 cells after CAT treatment. Levels of interleukin-17 and RORγt were assessed by qRT-PCR and enzyme-linked immunosorbent assay. The expression of signal transducer and activator of transcription 3 (STAT3) was determined by qRT-PCR and Western blot. RESULTS: We found that the proportion of Th17 cells was negatively associated with let-7g-5p expression in CIA mice. In in vitro experiments, CAT suppressed traditional differentiation of Th17 cells. Simultaneously, CAT significantly decreased Tregs-to-Th17 cells transdifferentiation. Our results demonstrated that CAT inhibited Tregs-to-Th17 cells transdifferentiation by up-regulating let-7g-5p and that the suppressive effect of CAT on traditional differentiation of Th17 cells is not related with let-7-5p. CONCLUSION: Our data indicate that CAT may be a potential modulator of Tregs-to-Th17 cells transdifferentiation by up-regulating let-7g-5p to reduce the expression of STAT3. These results provide new directions for research into RA treatment.