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BACKGROUND: The relationship between lifestyle and migraine is complex, as it remains uncertain which specific lifestyle factors play the most prominent role in the development of migraine, or which modifiable metabolic traits serve as mediators in establishing causality. METHODS: Independent genetic variants strongly associated with 20 lifestyle factors were selected as instrumental variables from corresponding genome-wide association studies (GWASs). Summary-level data for migraine were obtained from the FinnGen consortium (18,477 cases and 287,837 controls) as a discovery set and the GWAS meta-analysis data (26,052 cases and 487,214 controls) as a replication set. Estimates derived from the two datasets were combined using fixed-effects meta-analysis. Two-step univariable MR (UVMR) and multivariable Mendelian randomization (MVMR) analyses were conducted to evaluate 19 potential mediators of association and determine the proportions of these mediators. RESULTS: The combined effect of inverse variance weighted revealed that a one standard deviation (SD) increase in genetically predicted Leisure screen time (LST) was associated with a 27.7% increase (95% CI: 1.14-1.44) in migraine risk, while Moderate or/and vigorous physical activity (MVPA) was associated with a 26.9% decrease (95% CI: 0.61-0.87) in migraine risk. The results of the mediation analysis indicated that out of the 19 modifiable metabolic risk factors examined, hypertension explains 24.81% of the relationship between LST and the risk of experiencing migraine. Furthermore, hypertension and diastolic blood pressure (DBP) partially weaken the association between MVPA and migraines, mediating 4.86% and 4.66% respectively. CONCLUSION: Our research findings indicated that both LST and MVPA in lifestyle have independent causal effects on migraine. Additionally, we have identified that hypertension and DBP play a mediating role in the causal pathway between these two factors and migraine.
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Ejercicio Físico , Estudio de Asociación del Genoma Completo , Hipertensión , Análisis de la Aleatorización Mendeliana , Trastornos Migrañosos , Tiempo de Pantalla , Humanos , Trastornos Migrañosos/genética , Trastornos Migrañosos/epidemiología , Trastornos Migrañosos/fisiopatología , Ejercicio Físico/fisiología , Hipertensión/genética , Hipertensión/epidemiología , Actividades RecreativasRESUMEN
Numerous plant extracts used as feed additives in aquaculture have been shown to stimulate appetite, promote growth and enhance immunostimulatory and disease resistance in cultured fish. However, there are few studies on the famous Chinese herbal medicine Gelsemium elegans, which attracts our attention. In this study, we used the Megalobrama amblycephala to investigate the effects of G. elegans alkaloids on fish intestinal health after diet supplementation with 0, 5, 10, 20 and 40â¯mg/kg G. elegans alkaloids for 12 weeks. We found that dietary G. elegans alkaloids at 40â¯mg/kg improved intestinal morphology by increasing villus length, muscle thickness and villus number in the foregut and midgut and muscle thickness in the hindgut (Pâ¯<â¯0.05). These alkaloids also significantly improved intestinal antioxidant capabilities by increasing superoxide dismutase, catalase, total antioxidant capacity and malondialdehyde levels and up-regulated intestinal Cu/Zn-SOD and Mn-SOD (Pâ¯<â¯0.05) at 20 and 40â¯mg/kg. Dietary G. elegans alkaloids improved intestinal immunity via up-regulating the pro-inflammatory cytokines IL-1ß, IL-8, TNF-α and IFN-α and down-regulating expression of the anti-inflammatory cytokines IL-10 and TGF-ß (Pâ¯<â¯0.05) at 20 and 40â¯mg/kg. The expression of Toll-like receptors TRL1, 3, 4 and 7 were also up-regulated in intestine of M. amblycephala (Pâ¯<â¯0.05). In intestinal microbiota, the abundance of Proteobacteria was increased while the Firmicutes abundance was decreased at phylum level after feeding the alkaloids (Pâ¯<â¯0.05). The alkaloids also increased the abundance of the probiotic Rhodobacter and decreased the abundance of the pathogenic Staphylococcus at genus level (Pâ¯<â¯0.05). In conclusion, dietary G. elegans alkaloid supplementation promoted intestine health by improving intestine morphology, immunity, antioxidant abilities and intestinal microbiota in M. amblycephala.
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Antioxidantes/metabolismo , Cyprinidae/fisiología , Microbioma Gastrointestinal/efectos de los fármacos , Gelsemium/química , Inmunidad Innata/efectos de los fármacos , Extractos Vegetales/metabolismo , Alimentación Animal/análisis , Animales , Cyprinidae/microbiología , Dieta/veterinaria , Suplementos Dietéticos/análisis , Relación Dosis-Respuesta a Droga , Intestinos/anatomía & histología , Intestinos/efectos de los fármacos , Extractos Vegetales/administración & dosificación , Distribución AleatoriaRESUMEN
The present study aim to investigate the effects of dietary Gelsemium elegans alkaloids supplementation in Megalobrama amblycephala. A basal diet supplemented with 0, 5, 10, 20 and 40â¯mg/kg G. elegans alkaloids were fed to M. amblycephala for 12 weeks. The study indicated that dietary 20â¯mg/kg and 40â¯mg/kg G. elegans alkaloids supplementation could significantly improve final body weight (FBW), weight gain rate (WGR), specific growth rate (SGR), feed conversion ratio (FCR) and protein efficiency ratio (PER) (Pâ¯<â¯0.05). The 20â¯mg/kg and 40â¯mg/kg G. elegans alkaloids groups showed significantly higher whole body and muscle crude protein and crude lipid contents compared to the control group (Pâ¯<â¯0.05). The amino acid contents in muscle were also significantly increased in 20â¯mg/kg and 40â¯mg/kg groups (Pâ¯<â¯0.05). Dietary 40â¯mg/kg G. elegans alkaloids had a significant effect on the contents of LDH, AST, ALT, ALP, TG, TC, LDL-C, HDL-C, ALB and TP in M. amblycephala (Pâ¯<â¯0.05). Fish fed 20â¯mg/kg and 40â¯mg/kg dietary G. elegans alkaloids showed significant increase in complement 3, complement 4 and immunoglobulin M contents. The liver antioxidant enzymes (SOD, CAT and T-AOC) and MDA content significantly increased at 20â¯mg/kg and 40â¯mg/kg G. elegans alkaloids supplement (Pâ¯<â¯0.05). The mRNA levels of immune-related genes IL-1ß, IL8, TNF-α and IFN-α were significantly up-regulated, whereas TGF-ß and IL10 genes were significantly down-regulated in the liver, spleen and head kidney of fish fed dietary supplementation with 20â¯mg/kg and 40â¯mg/kg G. elegans alkaloids. After challenge with Aeromonas hydrophila, significant higher survival rate was observed at 20â¯mg/kg and 40â¯mg/kg G. elegans alkaloids supplement (Pâ¯<â¯0.05). Therefore, these results indicated that M. amblycephala fed a diet supplemented with 20â¯mg/kg and 40â¯mg/kg G. elegans alkaloids could significantly promote its growth performance, lipids and amino acids deposition, immune ability and resistance to Aeromonas hydrophila.
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Cyprinidae/inmunología , Resistencia a la Enfermedad/inmunología , Enfermedades de los Peces/prevención & control , Gelsemium/química , Extractos Vegetales/farmacología , Adyuvantes Inmunológicos/farmacología , Aeromonas hydrophila/fisiología , Alcaloides/química , Alcaloides/farmacología , Alimentación Animal/análisis , Animales , Cyprinidae/crecimiento & desarrollo , Dieta/veterinaria , Suplementos Dietéticos/análisis , Relación Dosis-Respuesta a Droga , Enfermedades de los Peces/inmunología , Proteínas de Peces/genética , Proteínas de Peces/metabolismo , Infecciones por Bacterias Gramnegativas/inmunología , Infecciones por Bacterias Gramnegativas/prevención & control , Infecciones por Bacterias Gramnegativas/veterinaria , Extractos Vegetales/químicaRESUMEN
Objectives: To perform a meta-analysis and network analysis identification to evaluate the efficacy, safety, and potential mechanisms of modified Baitouweng decoction (mBTWD) in the treatment of radiation enteritis. Methods: We searched PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang Databases, SionMed, and Chinese Scientific Journals Database to collect the randomized controlled trials (RCTs) of mBTWD treating radiation enteritis. Rev.Man 5.3 and Stata 14.0 software are employed for meta-analysis. The GRADE online tool is used to evaluate the quality of evidence. Network analysis and molecular docking approach are applied to predict the potential targets and ingredients of representative drugs in mBTWD for the treatment of radiation enteritis. Results: Seventeen studies are eventually included, covering a total of 1611 patients: (1) The clinical efficacy is significantly higher in mBTWD groups than in control groups (RR = 1.24, 95% CI (1.17, 1.32), P < 0.00001). (2) mBTWD has certain advantages in improving TCM syndromes (MD = -3.41, P < 0.00001). (3) mBTWD has a certain positive effect on the improvement of intestinal signs and symptoms (RR = 1.23, P=0.0001; OR = 3.51, P < 0.00001). (4) Indexes including CRP, KPS, and OB, are better in mBTWD groups than in control groups (P < 0.00001, P=0.002, P=0.03), but the credibility is downgraded for a small sample size. Adverse events and recurrence rates require further confirmation with larger sample sizes. (5) Univariate meta-regression for clinical efficacy shows none of the coefficients are significantly associated with the estimated risk ratio. The clinical efficacy overestimates about 4.9% from publication bias. The quality of the included studies is low according to GRADE evidence. (6) Quercetin, isorhamnetin, and beta-sitosterol are the main ingredients from representative drugs in mBTWD and its key targets are MYC, TP53, and MAPK14/MAPK1. Conclusions: mBTWD may be effective in the treatment of radiation enteritis, but its long-term benefits, safety, and molecular mechanisms remain unclear due to the poor quality of the evidence. Larger sample sizes, high-quality studies, and basic research are essential in the future.
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Objective: To systematically review the efficacy and safety of botanical drugs in the treatment of cancer-related fatigue (CRF) caused by gastric cancer (GC) and to determine the underlying pharmacological mechanisms using a network analysis. Methods: Databases such as China National Knowledge Infrastructure (CNKI), SinoMed, Wanfang, Pubmed, Embase, Cochrane Library, and Web of Science were searched for randomized controlled trials (RCTs) from inception to 18 April 2022. Methodological quality assessment was performed using the collaborative tool Cochrane, and data analysis were carried out using RevMan 5.4 and STATA 16 software. The botanical drugs with the highest frequency of use in the included studies was selected. The chemical composition, targets of action, disease targets, and shared targets of these botanical drugs were screened based on network analysis to explore the potential mechanisms of treating CRF in patients with gastric cancer (GC). Results: A total of 13 studies that included 986 patients with gastric CRF met the inclusion criteria. The results showed that botanical drugs could improve the CRF scores of gastric CRF, including the total scores of CRF dichotomous data [Odds Ratio (OR) = 4.22; 95% confidence interval (CI) 1.67-10.68; p = 0.002], the total scores of CRF continuous data [Standardized Mean Difference (SMD) = -0.98; 95% CI -1.36 to -0.60; p < 0.00001], the affective subscales of Piper Fatigue Scale (PFS) scores [Weighted Mean Difference (MD) = -0.79; 95%CI -0.92 to -0.65; p < 0.00001], the sensory subscales of PFS scores (MD = -0.57; 95%CI -0.77 to -0.37; p < 0.00001), the behavioral subscales of PFS scores (MD = -1.05; 95% CI -1.29 to -0.82; p < 0.00001), Quality of Life Questionnaire Core 30 (QLQ-C30) (MD = 10.53, 95% CI 8.26 to12.80; p < 0.00001), and the Karnofsky Performance Status scale (KPS) (MD = 5.18, 95% CI 2.60 to 7.76; p < 0.0001). The botanical drugs group had milder adverse effects than the control group. A total of 44 chemical components and 241 potential targets were obtained from the online database and 121 drug targets overlapped with the disease targets of CRF in patients with GC. Moreover, five key active ingredients, namely quercetin, Stigmasterol, luteolin, kaempferol, and isorhamnetin, as well as five key targets including AKT1, TP53, TNF, VEGFA, and CASP3, were screened. In addition, five key signaling pathways, including cancer, Hepatitis B, Prostate cancer, Hepatitis C, and Pancreatic cancer pathways, were obtained through enrichment analysis. Conclusion: The results of the study showed that botanical drugs have positive effects on CRF in patients with GC. However, more well-designed, multicenter, and large sample-sized Randomized Controlled Trials are required to evaluate the effectiveness of botanical drugs on CRF in patients with GC.
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Koumine is a component of the Chinese medicinal herb Gelsemium elegans and is toxic to vertebrates. We used the ciliate Tetrahymena thermophila as a model to evaluate the toxic effects of this indole alkaloid in eukaryotic microorganisms. Koumine inhibited T. thermophila growth and viability in a dose-dependent manner. Moreover, this drug produced oxidative stress in T. thermophila cells and expressions of antioxidant enzymes were significantly elevated at high koumine levels (p < 0.05). Koumine also caused significant levels of apoptosis (p < 0.05) and induced DNA damage in a dose-dependent manner. Mitophagic vacuoles were present in cells indicating induction of autophagy by this drug. Expression of ATG7, MTT2/4, CYP1 and HSP70 as well as the MAP kinase pathway gene MPK1 and MPK3 were significantly altered after exposed to koumine. This study represents a preliminary toxicological evaluation of koumine in the single celled eukaryote T. thermophila.
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Apoptosis/efectos de los fármacos , Daño del ADN , Alcaloides Indólicos/farmacología , Estrés Oxidativo/efectos de los fármacos , Tetrahymena thermophila/metabolismo , Apoptosis/genética , Regulación de la Expresión Génica/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/genética , Estrés Oxidativo/genética , Proteínas Protozoarias/biosíntesis , Proteínas Protozoarias/genética , Tetrahymena thermophila/genéticaRESUMEN
OBJECTIVE: To study the therapeutic effect of Weicao Capsule (WCC) on gout. METHODS: Two hundred gout patients were assigned to two groups. The treated group was treated with WCC and the control group was treated with Tongfengding Capsule. Both groups were given the respective treatments orally 3 times a day, 2 capsules each time with 2 weeks as one course and all patients received 2 successive courses of treatment. Changes of blood beta(2)-microglobulin (beta(2)-M), hemoglobin (Hb), 24 h urinary protein (24 h UP), pH value of urine and blood uric acid (BUA) as well as kidney function were observed. RESULTS: After treatment, level of beta(2)-M got lowered significantly, Hb and 24 h UP, blood urea nitrogen, serum creatinine and the clearance rate of creatinine, as well as blood lipids all improved obviously in the treated group (all P<0.01), while these parameters remained unchanged in the control group (P>0.05). The pH value of urine was improved in both groups showing an insignificant difference between them (P>0.05). BUA was decreased in both groups with a decrease to a larger extent in the treated group (P<0.01). The total effective rate was 87% in the treated group, which was superior to that in the control group (62%, P<0.05). CONCLUSION: WCC has a favorable therapeutic effect on gout and its mechanism of action for improving renal function and reducing urinary protein could be related with the lowering of blood beta(2)-M, BUA and lipids.