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Acupuncture has demonstrated its efficacy as a treatment for Parkinson's disease (PD). Thus, the objective of this study was to investigate the potential mechanisms underlying acupuncture's effects on PD treatment. Our approach involved several steps. Firstly, we assessed the behavioral changes in PD rats, the modulation of dopamine (DA) and 5-hydroxytryptamine (5-HT) levels in the striatum, as well as the alteration in α-synuclein (α-syn) levels in the midbrain, aiming to evaluate the efficacy of acupuncture in PD treatment. Secondly, we selected endoplasmic reticulum (ER) stress inhibitors and activators to assess the impact of ER stress on PD rats. Lastly, we utilized an IRE1 inhibitor to observe the influence of acupuncture on the IRE1/XBP1 pathway in PD rats. The findings of this study revealed that acupuncture improved the autonomous motor function, balance ability, coordination, and sensory motor integration function in the PD model rats. Additionally, it increased the levels of DA and 5-HT in the striatum while decreasing the levels of α-syn in the midbrain. Acupuncture also activated the expression of ER stress in the midbrain and upregulated the expression of IRE1/XBP1 in the striatum of PD model rats. Based on these results, we concluded that acupuncture may enhance the behavior of PD rats by activating the IRE1/XBP1 ER stress pathway, associated with the reduction of midbrain α-syn expression and the increase in striatal DA and 5-HT levels in unilateral 6-OHDA lesioned rats.
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Terapia por Acupuntura , Enfermedad de Parkinson , Animales , Ratas , Estrés del Retículo Endoplásmico , Enfermedad de Parkinson/terapia , Enfermedad de Parkinson/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Serotonina/metabolismoRESUMEN
BACKGROUND: It is unclear whether acupuncture has a rapid antidepressant effect and what is the main mechanism. METHODS: In this study, forced swimming stress test (FST) in mice were divided into five groups: control group, acupuncture group, scopolamine group, arecoline group, and acupuncture + arecoline group. Chronic unpredictable mild stress (CUMS) model rats were divided into six groups: naïve (non-CUMS) group, CUMS group, acupuncture group, scopolamine group, arecoline group, and acupuncture + arecoline group. Twenty-four hours after the end of treatment, FST was conducted in mice and rats. The expression of M1-AchR, AMPA receptors (GluR1 and GluR2), BDNF, mTOR, p-mTOR, synapsin I, and PSD95 in the prefrontal cortex was determined by western blot. The spine density of neurons in the prefrontal cortex was detected by golgi staining. RESULTS: The results showed that acupuncture reduced the immobility time of FST in two depression models. Acupuncture inhibited the expression of M1-AchR and promoted the expression of GluR1, GluR2, BDNF, p-mTOR, synapsin I, PSD95, and increased the density of neuron dendritic spine in the prefrontal cortex. CONCLUSIONS: The rapid antidepressant effect of acupuncture may be activating the "glutamate tide" - AMPA receptor activation - BDNF release - mTORC1 pathway activation through inhibiting the expression of M1-AchR in the prefrontal cortex, thereby increasing the expression of synaptic proteins and regulating synaptic plasticity.
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Terapia por Acupuntura , Depresión , Ratas , Ratones , Animales , Depresión/terapia , Depresión/metabolismo , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Sinapsinas/metabolismo , Arecolina/metabolismo , Arecolina/farmacología , Antidepresivos/farmacología , Antidepresivos/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Modelos Animales de Enfermedad , Escopolamina/farmacología , Corteza Prefrontal/metabolismo , Plasticidad Neuronal , Hipocampo/metabolismo , Estrés Psicológico/terapia , Estrés Psicológico/metabolismoRESUMEN
Importance: Tongxinluo, a traditional Chinese medicine compound, has shown promise in in vitro, animal, and small human studies for myocardial infarction, but has not been rigorously evaluated in large randomized clinical trials. Objective: To investigate whether Tongxinluo could improve clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI). Design, Setting, and Participants: Randomized, double-blind, placebo-controlled clinical trial was conducted among patients with STEMI within 24 hours of symptom onset from 124 hospitals in China. Patients were enrolled from May 2019 to December 2020; the last date of follow-up was December 15, 2021. Interventions: Patients were randomized 1:1 to receive either Tongxinluo or placebo orally for 12 months (a loading dose of 2.08 g after randomization, followed by the maintenance dose of 1.04 g, 3 times a day), in addition to STEMI guideline-directed treatments. Main Outcomes and Measures: The primary end point was 30-day major adverse cardiac and cerebrovascular events (MACCEs), a composite of cardiac death, myocardial reinfarction, emergent coronary revascularization, and stroke. Follow-up for MACCEs occurred every 3 months to 1 year. Results: Among 3797 patients who were randomized, 3777 (Tongxinluo: 1889 and placebo: 1888; mean age, 61 years; 76.9% male) were included in the primary analysis. Thirty-day MACCEs occurred in 64 patients (3.4%) in the Tongxinluo group vs 99 patients (5.2%) in the control group (relative risk [RR], 0.64 [95% CI, 0.47 to 0.88]; risk difference [RD], -1.8% [95% CI, -3.2% to -0.6%]). Individual components of 30-day MACCEs, including cardiac death (56 [3.0%] vs 80 [4.2%]; RR, 0.70 [95% CI, 0.50 to 0.99]; RD, -1.2% [95% CI, -2.5% to -0.1%]), were also significantly lower in the Tongxinluo group than the placebo group. By 1 year, the Tongxinluo group continued to have lower rates of MACCEs (100 [5.3%] vs 157 [8.3%]; HR, 0.64 [95% CI, 0.49 to 0.82]; RD, -3.0% [95% CI, -4.6% to -1.4%]) and cardiac death (85 [4.5%] vs 116 [6.1%]; HR, 0.73 [95% CI, 0.55 to 0.97]; RD, -1.6% [95% CI, -3.1% to -0.2%]). There were no significant differences in other secondary end points including 30-day stroke; major bleeding at 30 days and 1 year; 1-year all-cause mortality; and in-stent thrombosis (<24 hours; 1-30 days; 1-12 months). More adverse drug reactions occurred in the Tongxinluo group than the placebo group (40 [2.1%] vs 21 [1.1%]; P = .02), mainly driven by gastrointestinal symptoms. Conclusions and Relevance: In patients with STEMI, the Chinese patent medicine Tongxinluo, as an adjunctive therapy in addition to STEMI guideline-directed treatments, significantly improved both 30-day and 1-year clinical outcomes. Further research is needed to determine the mechanism of action of Tongxinluo in STEMI. Trial Registration: ClinicalTrials.gov Identifier: NCT03792035.
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Medicamentos Herbarios Chinos , Infarto del Miocardio con Elevación del ST , Femenino , Humanos , Masculino , Persona de Mediana Edad , Medicina Tradicional China , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio con Elevación del ST/tratamiento farmacológico , Accidente Cerebrovascular , Medicamentos Herbarios Chinos/uso terapéutico , Método Doble Ciego , Estudios de Seguimiento , Enfermedades CardiovascularesRESUMEN
Abnormal bone metabolism and subsequence osteoporotic fractures are common complications of chronic inflammatory diseases. No effective treatment for these bone-related complications is available at present. The chronic inflammatory state in these diseases has been considered as a key factor of bone loss. Therefore, the combination of inflammation inhibition and bone loss suppression may be an important strategy for reducing bone damage associated with inflammatory diseases. Bushen Huoxue Decoction (BSHXD) is a traditional Chinese herbal compound that has demonstrated the ability to improve bone quality and increase bone density. However, the efficacy of BSHXD on inflammatory bone loss and its underlying mechanisms remain unclear. This study aimed to investigate whether BSHXD inhibits inflammatory bone loss in mice and its potential molecular mechanisms. In the present study, the effect of BSHXD on lipopolysaccharide (LPS)-induced M1 polarization of RAW264.7 macrophage and on local inflammatory bone loss model of mouse skull was determined. The results showed that after treating RAW264.7 cells with LPS for 24 h, the expression levels of IL-1ß (39.42 ± 3.076 ng/L, p < 0.05), IL-6 (49.24 ± 1.766 mg/L, p < 0.05) and TNF-α (286.3 ± 27.12 ng/L, p < 0.05) were significantly increased. The addition of BSHXD decreased the expression levels of IL-1ß, IL-6, and TNF-α to 31.55 ± 1.296 ng/L, 37.94 ± 0.8869 mg/L, and 196.4 ± 25.25 ng/L, respectively (p < 0.05). The results of immunofluorescence staining, Western blotting (WB) and flow cytometry indicated that the proportion of M1 macrophages in RAW264.7 cells treated with BSHXD for 24 h was significantly lower than that in the LPS group (13.36% ± 0.9829% VS 24.80% ± 4.619%, p < 0.05). The evidence from in-vitro experiments showed that the immunomodulatory ability of BSHXD may be associated with the activation of AMP-dependent protein kinase (AMPK) pathway in LPS-treated macrophages. In addition, the results of micro-CT, H&E staining, immunohistochemical staining and immunofluorescence staining of mouse skull further demonstrated that BSHXD treatment significantly alleviated LPS-induced local bone loss and inflammatory damage in mouse skull model. All results indicated that BSHXD significantly inhibited inflammatory factors release and M1 polarization of macrophage through AMPK signaling pathway. Therefore, BSHXD may be a promising drug for the treatment of inflammatory bone loss.
RESUMEN
Acupuncture is a good treatment for depression in Parkinson's disease (DPD), so the possible mechanism of acupuncture in the treatment of DPD was explored in this study. Firstly, observing the behavioral changes of the DPD rat model, the regulation of monoamine neurotransmitters dopamine (DA) and 5-hydroxytryptamine (5-HT) in the midbrain, the change of α-synuclein (α-syn) in the striatum, the efficacy of acupuncture in the treatment of DPD was discussed. Secondly, autophagy inhibitors and activators were selected to judge the effect of acupuncture on autophagy in the DPD rat model. Finally, an mTOR inhibitor was used to observe the effect of acupuncture on the mTOR pathway in the DPD rat model. The results showed that acupuncture could improve the motor and depressive symptoms of DPD model rats, increase the content of DA and 5-HT, and decrease the content of É-syn in the striatum. Acupuncture inhibited the expression of autophagy in the striatum of DPD model rats. At the same time, acupuncture upregulates p-mTOR expression, inhibits autophagy, and promotes synaptic protein expression. Therefore, we concluded that acupuncture might improve the behavior of DPD model rats by activating the mTOR pathway, inhibiting autophagy from removing α-syn and repairing synapses.
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Terapia por Acupuntura , Enfermedad de Parkinson , Ratas , Animales , Enfermedad de Parkinson/terapia , Enfermedad de Parkinson/metabolismo , Depresión/terapia , Serotonina/farmacología , alfa-Sinucleína/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Sinapsis/metabolismo , Dopamina/farmacología , AutofagiaRESUMEN
Hyperprolactinemia is a common endocrine disease in women of reproductive age. Research has shown that patients with hyperprolactinemia often have decreased bone mineral density and an increased risk of fractures. However, there is still a lack of effective treatments. Paeoniflorin, one of the primary bioactive components in peony, is widely used in traditional Chinese medicine. Research has shown that paeoniflorin promotes osteoblast differentiation. However, whether paeoniflorin plays a role in hyperprolactinemia-induced osteoblastogenesis inhibition is not yet clear. In this study, we investigated the effect of paeoniflorin on prolactin (PRL)-mediated inhibition of osteoblast function. Our results showed that prolactin significantly reduced the expression of alkaline phosphatase (ALP), Osterix, and runt-related transcription factor 2 (RUNX2) in MC3T3-E1 cells cultured in an osteoblast differentiation medium, suggesting that prolactin inhibited osteoblast function. After treatment with paeoniflorin (PF), the expression of these osteoblast markers was upregulated. In addition, our findings proved that paeoniflorin increased the absorbance values of ALP-positive cells and the areas of alizarin red S (ARS) deposition compared to those in the prolactin group, suggesting that paeoniflorin reversed the PRL-induced reduction in osteoblast differentiation. The PRL-induced activation of nuclear factor kappa B (NF-κB) was significantly reversed by paeoniflorin, indicating that paeoniflorin promoted osteoblast function by inhibiting the NF-κB signaling pathway. In summary, these results showed that paeoniflorin alleviated the inhibitory effect of prolactin on osteoblastogenesis by suppressing the NF-κB signaling pathway.
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Selenium is an essential element but toxic at high levels in animals. The effects of Se on growth performance and the immune system in Nile tilapia remain inconclusive. In this study, Nile tilapia Oreochromis niloticus was fed on selenium yeast (Se(Y))- and selenite (Se(IV))-enriched feed at 0, 3, 6, and 12 µg/g (dry wt) for 45 and 90 d. The growth, bioaccumulation, biochemical markers related to antioxidant, immunological, nervous and digestive systems were evaluated in various fish tissues (liver, intestine, kidney, muscle, brain, spleen, gills). The results showed that the accumulation of Se(Y) was 1.3-2 folds of Se(IV) in most tissues. The growth of tilapia was enhanced by both Se(Y) and Se(IV) at 3 µg/g after 90 d, with Se(Y) better than Se(IV) in tilapia feed. After 45 d, the levels of lipid peroxidation, the activity of the antioxidant enzymes, and the transcriptional levels of the immune related genes (IL-1ß, IFN-γ and TNF-α) and stress proteins (HSP70 and MT) were enhanced in all treatments, except that of MT in the 12 µg/g Se(Y) group. In addition, both Se species inhibited the activity of acetylcholinesterase (AChE) in the brain and one digestive enzyme α-glucosidase (α-Glu) in the intestine at 12 µg/g. However, after 90 d, the effects on most biochemical markers were less pronounced, implying a possible acclimation after prolonged duration. The results demonstrate Se is beneficial to O. niloticus at low levels and toxic at elevated levels. The immunostimulation by Se might be greatly weakened after long term feeding Se-enriched feed. This study helps to better understand the effects of Se on the antioxidant and immune systems and to establish the optimal Se levels in the feed and duration for O. niloticus.
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Antioxidantes/metabolismo , Bioacumulación , Cíclidos/inmunología , Inmunidad Innata/efectos de los fármacos , Ácido Selenioso/metabolismo , Selenio/metabolismo , Levadura Seca/metabolismo , Alimentación Animal/análisis , Animales , Dieta/veterinaria , Suplementos Dietéticos/análisis , Relación Dosis-Respuesta a Droga , Ácido Selenioso/administración & dosificación , Selenio/administración & dosificación , Factores de Tiempo , Levadura Seca/administración & dosificaciónRESUMEN
BACKGROUND: Iodine deficiency in pregnant women, defined as a median urinary iodine concentration (UIC) of less than 150 µg/L, is an important public health issue. To improve their iodine intake, it is important to understand the knowledge and practices regarding iodine. METHODS: A cross-sectional investigation was conducted on 2642 pregnant women during 2016â»2017 in Zhejiang province, China. A 3-point Likert scale questionnaire was used to record knowledge. The UIC and iodine content in household salt were determined. RESULTS: Coastal participants were iodine deficient (median UIC 127.6 µg/L) while inland participants were iodine sufficient (median UIC 151.0 µg/L). The average knowledge scores were significantly lower for the coastal participants (24.2 points vs. 25 points for the inland participants; p < 0.001). The percentage for iodized salt consumption was significantly lower for the coastal participants (88.9% vs. 96.0% for those inland; p < 0.001). A generalized linear model analysis showed that non-iodized salt consumption, coastal region, and low knowledge scores were independently associated with a low UIC. CONCLUSIONS: Comprehensive interventional strategies are needed to develop to achieve an optimal iodine status. We recommend that coastal pregnant women should take iodine supplements based on the consumption of iodized salt, and improvement of iodine-related knowledge.
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Ingestión de Alimentos/psicología , Conocimientos, Actitudes y Práctica en Salud , Yodo/deficiencia , Complicaciones del Embarazo/psicología , Mujeres Embarazadas/psicología , Adolescente , Adulto , China , Estudios Transversales , Femenino , Humanos , Yodo/análisis , Yodo/orina , Estado Nutricional , Embarazo , Complicaciones del Embarazo/etiología , Complicaciones del Embarazo/orina , Cloruro de Sodio Dietético/análisis , Sodio en la Dieta/análisis , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Zhejiang introduced universal salt iodization (USI) programme in 1995 and has achieved the goal of elimination of iodine deficiency disorders (IDD) since 2011. However, no systematical data of iodine nutritional status in population in pregnancy is available. In this cross-sectional study, pregnant women were interviewed to complete questionnaires in addition to handing in samples of urine and household table salt between March 2016 to February 2017. Date of birth, age of pregnancy, ethnicity and dietary iodine habits were recorded. The overall median urinary iodine concentration in 8561 pregnant women was 130.47 µg/L, which was lower than the cut-off value of iodine sufficiency of 150 µg/L recommended by the WHO. Participants using non-iodized salt, taking non-iodine-containing supplements, in coastal and in Han group were independently associated with iodine deficiency. The current USI programme did not supply Zhejiang pregnant women with sufficient iodine intake. They are generally iodine deficient, which have great public health importance since even mild IDD in pregnancy have adverse effects on fetal neurodevelopment. We strongly recommend urgent measures to improve iodine intake in pregnancy.
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Yodo/deficiencia , Desnutrición/epidemiología , Complicaciones del Embarazo/epidemiología , Oligoelementos/deficiencia , China/epidemiología , Estudios Transversales , Femenino , Humanos , Yodo/administración & dosificación , Yodo/orina , Embarazo , Cloruro de Sodio Dietético/administración & dosificación , Encuestas y Cuestionarios , Orina/químicaRESUMEN
OBJECTIVE: To study the glycosides from Guangdong Liangcha Granules. METHODS: The chemical constituents were isolated by various chromatographic techniques and the structures of chemical constituents were identified by spectroscopic analysis and literature. RESULTS: Six compounds were isolated and identified as ilexoside B (1), asprellanosides B (2), asprellanoside A (3), 4', 5 ,7 -tri- hydroxyflavone-6-O-ß3-D-glucopyranosyl ester(4), isoviolanthin (5),3-O-methy-lellagic acid 4'-O-rhamnopyranoside (6). CONCLUSION: Compounds 1 - 5 are firstly obtained from Guangdong Liangcha Granules.
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Medicamentos Herbarios Chinos/química , Glicósidos/análisis , Saponinas , TriterpenosRESUMEN
Six new triterpenoid saponins, psychotrianosides A-F (1-6), and two known triterpenoid saponins, psychotrianoside G (7) and ardisianoside D (8), were isolated from Psychotria sp. Their structures were determined mainly by spectroscopic methods. The cytotoxic activities of 1-8 against five human cancer cell lines (MDA-MB-231, MCF-7, MCF-7/ADM, HepG2, and HepG2/ADM) are reported for the first time. Psychotrianoside C (3) showed the most potent antiproliferative activity among these saponins, and the IC50 value of 3 against MDA-MB-231 was 2.391 ± 0.161 µM. Compound 3 was also found to induce apoptosis.
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Antineoplásicos Fitogénicos/farmacología , Psychotria/química , Saponinas/farmacología , Triterpenos/farmacología , Antineoplásicos Fitogénicos/química , Apoptosis , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Concentración 50 Inhibidora , Espectroscopía de Resonancia Magnética , Estructura Molecular , Tallos de la Planta/química , Saponinas/química , Saponinas/aislamiento & purificación , Análisis Espectral , Triterpenos/química , Triterpenos/aislamiento & purificaciónRESUMEN
Residue of azole antifungals in the environment is of concern due to the environmental risks and persistence. Distribution, behavior, and fate of frequently used azole antifungal pharmaceuticals were investigated in wastewater at two sewage treatment plants (STPs) in China. Fluconazole, clotrimazole, econazole, ketoconazole, and miconazole were constantly detected at 1-1834 ng L(-1) in the wastewater. The latter four were also ubiquitously detected in sewage sludge. Fluconazole passed through treatment in the STPs and largely remained in the final effluent. On the contrary, biotransformation and sorption to sludge occurred to the other azoles. Ketoconazole was more readily bio-transformed, whereas clotrimazole, econazole, and miconazole were more likely to be adsorbed onto and persisted in sewage sludge. Lipophilicity plays the governing role on adsorption. The highest concentrations in the raw wastewater were observed in winter for the azole pharmaceuticals except for fluconazole. The seasonal difference was smoothed out after treatment in the STPs.
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Antifúngicos/análisis , Azoles/análisis , Eliminación de Residuos Líquidos/métodos , Contaminantes Químicos del Agua/análisis , Antifúngicos/química , Azoles/química , Biodegradación Ambiental , China , Clotrimazol/análisis , Clotrimazol/química , Econazol/análisis , Econazol/química , Monitoreo del Ambiente , Fluconazol/análisis , Fluconazol/química , Cetoconazol/análisis , Cetoconazol/química , Miconazol/análisis , Miconazol/química , Aguas del Alcantarillado/química , Contaminantes Químicos del Agua/químicaRESUMEN
OBJECTIVE: To investigate the association of serum levels of hyaluronic acid (HA), tumor necrosis factor-alpha (TNF-alpha), vascular endothelial growth factor (VEGF), NO, and Se with the clinical manifestations in adult patients with Kashin-Beck disease (KBD). METHODS: Total 216 adults were selected for KBD screening from the KBD-prevalent areas in Yongshou county and the non-KBD areas of Chang'an county, Xi'an city, ShaanXi Province. According to the National Diagnostic Criteria of Kashin-Beck Disease in China, the diagnoses of KBD was established in 25 adult patients (11 men and 14 women, average age of 47.88+/-11.16 years), and 20 healthy control subjects from the KBD areas (8 men and 12 women, average age of 47.85+/-12.05 years) and 20 from the non-KBD areas (8 men and 12 women, average age of 47.45+/-11.24 years) were also selected to serve as controls. There was no significant difference in the average age and gender distribution between the 3 groups. The serum levels of HA, TNF-alpha, VEGF, NO and Se were measured by enzyme-linked immunosorbent assay, nitrate reductase method and griphite furnace atomic absorption spectrometry. RESULTS: Serum NO level was significantly higher in KBD group (41.7+/-21.89 micromol/L) than in the health controls from KBD areas (17.1+/-13.01 micromol/L) and non-KBD areas (17.58+/-11.48 micromol/l, F=13.11, df=2, P<0.001). Serum TNF-alpha level in KBD group (32.7+/-3.55 pg/ml) was significantly higher than that in the control subjects from the non-KBD areas (30.95+/-2.22 pg/ml, F=3.672, df=2, P=0.031), but similar with the control subjects from the KBD areas (32.7+/-3.55 pg/ml). Serum TNF-alpha and NO levels were identified as the indices that differed between adult KBD patients and the controls from both KBD and non-KBD areas by differential analysis (the function of differentiation was 0.062xNO+0.173xTNF -7.218). CONCLUSION: Serum TNF-alpha and NO levels are significantly increased in adult KBD patients and are associated with the clinical manifestations of KBD.