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Central nervous system (CNS) diseases have become one of the leading causes of death in the global population. The pathogenesis of CNS diseases is complicated, so it is important to find the patterns of the disease to improve the treatment strategy. Microglia are considered to be a double-edged sword, playing both harmful and beneficial roles in CNS diseases. Therefore, it is crucial to understand the progression of the disease and the changes in the polar phenotype of microglia to provide guidance in the treatment of CNS diseases. Microglia activation may evolve into different phenotypes: M1 and M2 types. We focused on the roles that M1 and M2 microglia play in regulating intercellular dialogues, pathological reactions and specific diseases in CNS diseases. Importantly, we summarized the strategies used to modulate the polarization phenotype of microglia, including traditional pharmacological modulation, biological therapies, and physical strategies. This review will contribute to the development of potential strategies to modulate microglia polarization phenotypes and provide new alternative therapies for CNS diseases.
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Doenças do Sistema Nervoso Central , Microglia , Humanos , Microglia/patologia , Doenças do Sistema Nervoso Central/terapia , Doenças do Sistema Nervoso Central/patologia , FenótipoRESUMO
Evodia rutaecarpa, the near-ripe fruit of Euodia rutaecarpa (Juss.) Benth, Euodia rutaecarpa (Juss.) Benth. var. officinalis (Dode) Huang, or Euodia rutaecarpa (Juss.) Benth. var. bodinieri (Dode) Huang, is a famous herbal medicine with several biological activities and therapeutic values, which has been applied for abdominalgia, abdominal distension, vomiting, and diarrhea as a complementary and alternative therapy in clinic. Indole alkaloids, particularly evodiamine (EVO), rutaecarpine (RUT), and dedhydroevodiamine (DHE), are received rising attention as the major bioactivity compounds in Evodia rutaecarpa. Therefore, this review summarizes the physicochemical properties, pharmacological activities, pharmacokinetics, and therapeutic effects on gastrointestinal diseases of these three indole alkaloids with original literature collected by PubMed, Web of Science Core Collection, and CNKI up to June 2023. Despite sharing the same parent nucleus, EVO, RUT, and DHE have different structural and chemical properties, which result in different advantages of biological effects. In their wide range of pharmacological activities, the anti-migratory activity of RUT is less effective than that of EVO, and the neuroprotection of DHE is significant. Additionally, although DHE has a higher bioavailability, EVO and RUT display better permeabilities within blood-brain barrier. These three indole alkaloids can alleviate gastrointestinal inflammatory in particular, and EVO also has outstanding anti-cancer effect, although clinical trials are still required to further support their therapeutic potential.
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Evodia , Gastroenteropatias , Plantas Medicinais , Humanos , Evodia/química , Alcaloides Indólicos/farmacologia , Alcaloides Indólicos/uso terapêutico , Plantas Medicinais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Extratos Vegetais/análise , Gastroenteropatias/tratamento farmacológico , Frutas/químicaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Tou Nong Powder (TNP), a classical Chinese medicinal formula originated from the Chinese Ming Dynasty, has been applied to treat skin ulcers in patients with deficient constitutions. According to theory of traditional Chinese medicine, colonic ulcers share similar pathological conditions with skin ulcers, and consequently, TNP has been applied to ulcerative colitis (UC) safely and effectively. AIM OF STUDY: To investigate whether TNP obstructs 2,4,6-trinitrobenzene sulfonic acid (TNBS) induced enteric inflammation through regulation of NLRP3 inflammasome and attenuating enteric pyroptosis. MATERIALS AND METHODS: Network pharmacology and UPLC-Q-TOF/MS were operated to identify compounds and pharmacological potential targets. The therapeutic effects of TNP were assessed on TNBS induced colitis via general symptoms (disease activity index, colonic weight and length) and histopathological observation. The NF-κB/NLRP3/Caspase-1/GSDMD signaling pathway regulation was investigated by Western blot and real time reverse transcription polymerase chain reaction (RT-qPCR). RESULTS: TNP ameliorates the disease activity index, reverses the increase of colonic weight increase, alleviates colonic shortening and colonic histopathological injury. A decrease in tumor necrosis factor α (TNF-α), diamine oxidase (DAO), intercellular adhesion molecule-1 (ICAM-1), and endo-toxin (ET) were investigated in peripheral circulation. Moreover, TNP significantly obstructed the NF-κB/NLRP3/Caspase-1/GSDMD signaling pathway. CONCLUSION: TNP displays a promising therapeutic effect on UC via suppressing NF-κB/NLRP3/Caspase-1/GSDMD signaling pathway and reducing the expression of IL-1ß and IL-18.
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Colite Ulcerativa , Colite , Humanos , Inflamassomos/metabolismo , NF-kappa B/metabolismo , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Pós/uso terapêutico , Caspase 1/metabolismo , Colite/tratamento farmacológico , Proteínas de Ligação a Fosfato , Proteínas Citotóxicas Formadoras de Poros/metabolismoRESUMO
Autonomic imbalance is a core aspect of stress response that strongly correlates to cardiovascular diseases. Enhanced activity of the central corticotropin-releasing hormone (CRH) system may result in autonomic imbalance to cause cardiovascular responses in a stress state. Electroacupuncture at PC6 acupoints has been demonstrated to prevent and treat cardiovascular diseases. In this study, we aim to demonstrate the protective role of electroacupuncture at PC6 in ameliorating cardiac autonomic imbalance and investigate the underlying mechanisms in immobilization stress rats. Four groups were subjected. Immobilization stress was applied to three groups. And the rats in two electroacupuncture-intervened groups exerted electroacupuncture at PC6 or tail respectively. Then, we performed ECG recording for heart rate variability (HRV) analysis, and rats were sacrificed after experiments for biological analysis. HRV analysis indicated that electroacupuncture at PC6 improved the enhanced low-frequency band of the power spectrum (LF), the reduced high-frequency band of the power spectrum (HF), and the enhanced LF/HF ratio caused by immobilization stress. Besides, electroacupuncture at PC6 significantly decreased phosphorylated tyrosine hydroxylase expression and increased acetylcholine esterase expression in heart of immobilization stress rats. Furthermore, electroacupuncture at PC6 significantly decreased CRH level and CRH 1 type receptor and CRH 2 type receptor (CRHR2) expressions in the rostral ventrolateral medulla (RVLM), and CRH level and CRHR2 expression in the nucleus of the solitary tract (NTS) of immobilization stress rats. Our findings suggest that electroacupuncture at PC6 can ameliorate stress-induced cardiac autonomic imbalance by modulating the CRHergic input in the RVLM and NTS.
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Doenças Cardiovasculares , Eletroacupuntura , Ratos , Animais , Hormônio Liberador da Corticotropina/metabolismo , Eletroacupuntura/métodos , Coração , Núcleo Solitário/metabolismoRESUMO
Stress can trigger cardiovascular disease. Both imbalance of autonomic nervous activity and increase of neurohormonal output are core aspects of stress responses and can lead to cardiovascular disease. PC6 as a very important acupoint is used to prevent and treat cardiovascular disease and to improve stress-related activities. We examined the influence of electroacupuncture (EA) at PC6 on stress-induced imbalance of autonomic nervous activity and increase of neurohormonal output. EA at PC6 relieved increased cardiac sympathetic nervous activity and decreased cardiac vagal nervous activity induced by immobilization stress. Also, EA at PC6 reduced immobilization stress-induced increases of plasma norepinephrine (NE) and adrenaline (E) released from sympatho-adrenal-medullary axis. Finally, EA at PC6 reduced immobilization stress-induced increases of corticotropin-releasing hormone (CRH) in paraventricular hypothalamic nucleus and plasma cortisol (CORT) released from hypothalamic-pituitary-adrenal axis. However, EA at tail had no significant effect on the stress-induced autonomic and neuroendocrine responses. The results demonstrate the role of EA at PC6 regulating the autonomic and neuroendocrine responses induced by stress and provide insight into the prevention and treatment of EA at PC6 for stress-induced cardiovascular disease by targeting autonomic and neuroendocrine systems.
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Background: Tong-fu therapeutic method (TFTM) is a traditional Chinese medicine treatment method for ulcerative colitis, which is a novel treatment strategies and have purgative effect. As the most representative medicinal of TFTM, Rhubarb has been reported to have a therapeutic impact on ulcerative colitis by regulating intestinal flora, anti-inflammation, and improving intestinal microcirculation. Although rhubarb has been widely used in Chinese medicine for the treatment of ulcerative colitis, the appropriate protocol is still demanded to its rational use in clinic, which promoted to evaluate the efficacy and safety for rhubarb-based therapy on ulcerative colitis. Method: Clinical trials were searched through PubMed, Cochrane Library, Web of Science, Excerpta Medica Database, Chinese National Knowledge Infrastructure, WAN FANG Database, Chinese Scientific Journal Database, and Chinese Biomedical Literature Database. The subgroup analyses were performed with three groups: medication, course of treatment, and route of administration. The statistical analyses were performed on Review Manager software (version 5.4.1). Results: A total of 2, 475 patients in 30 original studies were analyzed in this article. It was found that rhubarb-based therapy could increase clinical efficacy and reduce the recurrence rate. Subgroup analyses showed that rhubarb-based therapy was more effective than 5-aminosalicylic acid or sulfasalazine alone. In addition, the hypercoagulable state of ulcerative colitis could be ameliorated by decreasing platelet (PLT) and fibrinogen (FIB), and increasing prothrombin time (PT) significantly. Moreover, C-reaction protein (CRP), tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-8, and IL-1ß expression were significantly reduced, while IL-10 production was increased, which mediated the alleviation of intestinal inflammation stress. Conclusion: Rhubarb-based therapy could effectively improve ulcerative colitis. Of note, the rhubarb-based medicinal formulas combined with 5-ASA or SASP are more effective than the 5-ASA or SASP alone. In addition, although rhubarb has side effect, the results of our analysis showed that rhubarb-based therapy did not exhibit significant side effects. This means it has a high safety profile in clinical use. Moreover, the use of rhubarb-based therapy is recommend to use within 1-13 weeks or 3 months via administered orally or by enema, which is contributes to ensure the curative effect and avoid its toxic and side effects. As an important case of TFTM, rhubarb-based therapy provides evidence for the practical application of TFTM.
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Objective: To analyze the effectiveness of nursing risk management in neonatal asphyxia resuscitation care and to observe and summarize the nursing measures and outcomes. Methods: A total of 60 neonatal asphyxia cases from January 2021 to December 2021 were recruited and assigned via a random number table method at a ratio of 1 : 1 to receive either routine care plus nursing risk management (the observation group, n = 30) or routine care (the control group, n = 30). Outcome measures included blood gas index, neonatal Apgar score, neonatal behavioral neurological assessment (NBNA) score, nursing satisfaction, and complications. Results: The differences in partial pressure of oxygen (PaO2) and partial pressure of carbon dioxide (PaCO2) between the two groups before care were not statistically significant (P > 0.05), while after care, PaO2 in the observation group had a higher level of PaO2 and a lower level of PaCO2 than the control group (P < 0.01). The two groups showed similar Apgar scores and NBNA scores before care (P > 0.05), while after care, routine care plus nursing risk management resulted in higher Apgar scores and NBNA scores versus routine care alone (P < 0.01). The nursing satisfaction rate in the observation group (96.67%) was significantly higher than that of the control group (73.33%) (P=0.030). Nursing risk management plus routine care was associated with a significantly lower incidence of complications (6.67%) compared to routine care (26.67%) (P=0.038). Conclusion: Nursing risk management in neonatal asphyxia resuscitation care showed outstanding outcomes in improving neonatal blood gas index, neurological function, and Apgar score, while reducing the occurrence of complications and achieving high nursing satisfaction.
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Purpose: To evaluate the efficacy of the Sanyin formula (SYF) plus conventional standard chemotherapy in operable triple-negative breast cancer (TNBC) patients, a randomized controlled trial was implemented at 5 hospitals and cancer centers in China between May 23, 2016, and October 31, 2019. Materials and Methods: Female patients aged 18 to 80 years with operable TNBC after definitive surgery were screened and enrolled. The exclusion criteria included metastatic disease, other tumors, or locally advanced disease. Patients were randomly divided into groups SYF plus conventional standard chemotherapy and placebo plus conventional standard chemotherapy at a ratio of 1:1. The primary endpoint of the investigation was disease-free survival (DFS), and secondary endpoints included overall survival (OS) and toxicity. Results: A total of 252 operable female TNBC patients were randomized to receive SYF plus conventional standard chemotherapy (N = 127) or a placebo plus conventional standard chemotherapy (N = 125). At a median follow-up of 51 months, 5-year DFS time was longer in those assigned to SYF plus conventional standard chemotherapy compared with placebo plus conventional standard chemotherapy (94.2%vs 85.5%, hazard ratio [HR] = 0.40; 95%CI, 0.17-0.97; P = 0.034). The absolute benefit for 5-year DFS was 8.7% in the SYF plus conventional standard chemotherapy group. No statistically significant difference was observed in OS between the two groups (P = 0.23). Patients with negative node status benefited more from SYF plus conventional standard chemotherapy treatment (HR = 0.21, P-interaction = 0.013) in accordance with the exploratory subgroup analyses of DFS. Conclusions: The results of the present study suggest that the traditional Chinese medicine SYF plus conventional chemotherapy regimens is an effective alternative adjuvant chemotherapy strategy for female operable TNBC patients. Clinical Trial Registration: https://www.chictr.org.cn/searchproj.aspx, identifier ChiCTR-IPR-16008590.
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[This corrects the article DOI: 10.3389/fmed.2021.766126.].
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Background: The combination of probiotics and traditional Chinese medicine (TCM) is a prospective therapy for ulcerative colitis (UC), and its efficacy and safety need to be urgently evaluated. Objective: This study aims to comprehensively assess the efficacy and safety of probiotics combined with TCM for the treatment of UC. Methods: The Pubmed, EMBASE, Cochrane library, China Academic Journals (CNKI), Wan-fang database, Chinese biomedical literature service system (CBM), and Chinese Science and Technology Journals (CQVIP) were searched. Subgroup analysis were designed in accordance with different control drugs, treatment courses, and types of probiotics. The Review Manager software (version 5.4.1) was utilized for statistical analysis. Results: 14 original studies containing 1,154 patients were analyzed and showed that probiotics with TCM was more effective than 5-aminosalicylic acid (5-ASA), probiotics or TCM used individually. Moreover, probiotics combined with TCM could inhibit the intestinal inflammation, reduce the recurrence rate and the incidence of adverse events. The subgroup analysis showed that a mixture of different probiotics was more effective than a single strain. Conclusion: It is suggested that probiotics combined with TCM could effectively control clinical symptoms, inhibit intestinal inflammatory response, and finally slow down the disease progress and reduce the disease recurrence with less adverse events. The mixture of different probiotics used in conjunction with individually tailored TCM is a potential clinical strategy for UC.
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[This corrects the article DOI: 10.3389/fphar2021.714287.].
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Ulcerative Colitis (UC) is a chronic inflammatory bowel disease. The prolonged course of UC and the lack of effective treatment management make it difficult to cure, affecting the health and life safety of patients. Although UC has received more attention, the etiology and pathogenesis of UC are still unclear. Therefore, it is urgent to establish an updated and comprehensive understanding of UC and explore effective treatment strategies. Notably, sufficient evidence shows that the intestinal microbiota plays an important role in the pathogenesis of UC, and the treating method aimed at improving the balance of the intestinal microbiota exhibits a therapeutic potential for UC. This article reviews the relationship between the genetic, immunological and microbial risk factors with UC. At the same time, the UC animal models related to intestinal microbiota dysbiosis induced by chemical drugs were evaluated. Finally, the potential value of the therapeutic strategies for restoring intestinal microbial homeostasis and treating UC were also investigated. Comprehensively, this study may help to carry out preclinical research, treatment theory and methods, and health management strategy of UC, and provide some theoretical basis for TCM in the treatment of UC.
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Background: The combination of strengthening Qi and eliminating pathogens is an available therapeutic principle in traditional Chinese medicine (TCM) for primary liver cancer (PLC) at middle-advanced stage. However, there is a lack of reasonable evidence to support the proper application of this therapeutic principle. This meta-analysis aims to evaluate the efficacy and safety of Chinese medicinal formulas (CMFs), including two subgroup analyses of the principle of strengthening Qi and eliminating pathogens. Method: Clinical trials were obtained through searching of EMBASE, Web of Science, PubMed, Cochrane Library, Chinese National Knowledge Infrastructure, Wanfang Database, Chinese Scientific Journal Database, Chinese Biomedical Literature Database, and two clinical trial registries. The randomized controlled trials with the combination of CMFs and transcatheter arterial chemoembolization (TACE) in the experiment group were acceptable, in contrast to the TACE alone in the control group. The statistics analysis was performed on Review Manager 5.4. Results: A total of eligible 24 trials were accessed in this work. Overall, CMFs could improve the survival duration of 6 months, 1 year, and 2 years, Karnofsky Performance Status, tumor objective response rate (ORR), AFP, and symptom. In the subgroup analysis, trials complying with the principle of single strengthening Qi did not show any significant difference in increasing tumor ORR. Meanwhile, the principle of combined strengthening Qi and eliminating pathogens was uncertain in improving symptoms and 1-year and 2-year survival time. In addition, the outcome indexes of ALT and AST were heterogeneous. In last, the total occurrence of adverse events could not be reduced via using CMFs. Patients treated with CMFs exhibited liver injury, fever, and white blood cell decline, with mild events occurring more frequently and severe events occurring less. Conclusion: CMFs are an effective treatment method to cure PLC at the middle-advanced stage. Adopting the principle of single strengthening Qi presents better efficacy in the long term by prolonging the survival duration. Following the principle of combined strengthening Qi and eliminating pathogens could be more beneficial to patients in short term by lessening the tumor size. CMFs have the advantage of reducing certain serious adverse events.
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Osteoporosis is the most common osteolytic disease characterized by excessive osteoclast formation and resultant bone loss, which afflicts millions of patients around the world. Astilbin, a traditional herb, is known to have anti-inflammatory, antioxidant and antihepatic properties, but its role in osteoporosis treatment has not yet been confirmed. In our study, astilbin was found to have an inhibitory effect on the RANKL-induced formation and function of OCs in a dose-dependent manner without cytotoxicity. These effects were attributed to its ability to suppress the activity of two transcription factors (NFATc1 and c-Fos) indispensable for osteoclast formation, followed by inhibition of the expression of bone resorption-related genes and proteins (Acp5/TRAcP, CTSK, V-ATPase-d2 and integrin ß3). Furthermore, we examined the underlying mechanisms and found that astilbin repressed osteoclastogenesis by blocking Ca2+ oscillations and the NF-κB and MAPK pathways. In addition, the therapeutic effect of MA on preventing bone loss in vivo was further confirmed in an ovariectomized mouse model. Therefore, considering its ability to inhibit RANKL-mediated osteoclastogenesis and the underlying mechanisms, astilbin might be a potential candidate for treating osteolytic bone diseases.
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Reabsorção Óssea/prevenção & controle , Flavonóis/farmacologia , Osteoclastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Ligante RANK/farmacologia , Animais , Células Cultivadas , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Expressão Gênica/efeitos dos fármacos , Humanos , Integrina beta3/genética , Integrina beta3/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Fatores de Transcrição NFATC/metabolismo , Osteoclastos/metabolismo , Osteogênese/genética , Ovariectomia , Fitoterapia/métodos , Proteínas Proto-Oncogênicas c-fos/metabolismo , Células RAW 264.7 , Fosfatase Ácida Resistente a Tartarato/genética , Fosfatase Ácida Resistente a Tartarato/metabolismoRESUMO
Deregulation of the Wnt signaling pathway leads to colorectal cancer progression. Natural dietary compounds serve as promising candidates for development as chemopreventive agents by suppressing the Wnt/ß-catenin signaling pathway. Physalis peruviana-derived 4ßHWE showed a significant inhibitory activity with a calculated IC50 of 0.09 µΜ in a screening of novel inhibitors of Wnt signaling with the dual-luciferase reporter assay. This study investigated the anti-tumor effect of 4ßHWE and the potential Wnt signaling inhibitory mechanism. Both the western blot analysis and immunofluorescence assay showed that 4ßHWE promoted the phosphorylation and degradation of ß-catenin and the subsequent inhibition of its nuclear translocation to attenuate the endogenous Wnt target gene expression in colorectal cancer (CRC) cells. The cell viability assay indicated that 4ßHWE preferentially inhibited the proliferation of CRC compared with CCD-841-CoN, a normal human colonic epithelial cell line. 4ßHWE-mediated G0/G1 cell cycle arrest and apoptosis induction contributed to the suppression of the proliferation of CRC in the cell cycle and Annexin V-FITC/Propidium Iodide apoptosis analysis. Moreover, in vivo, 4ßHWE dramatically inhibited tumor growth in HCT116 xenografts by attenuating the Wnt/ß-catenin signaling pathway. In conclusion, our study suggested that 4ßHWE could be of potential use in anti-tumor agent development as a novel Wnt signaling inhibitor.
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Antineoplásicos Fitogênicos/farmacologia , Physalis/química , Extratos Vegetais/farmacologia , Vitanolídeos/farmacologia , Via de Sinalização Wnt/efeitos dos fármacos , Animais , Antineoplásicos Fitogênicos/química , Apoptose/efeitos dos fármacos , Biomarcadores , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias Colorretais/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Humanos , Camundongos , Estrutura Molecular , Extratos Vegetais/química , Relação Estrutura-Atividade , Vitanolídeos/químicaRESUMO
This study was focused on investigating the effect of lentinan (LNT) on the expression patterns of ß-catenin, Bcl-2, and Bax in murine bone marrow cells (BMCs). Adult BALB/L mice were divided into four groups (n = 10 for each group) that consisted of normal control adult BALB/L mice (control group) and adult BALB/L mice with intraperitoneal injection of low, medium, and high doses of LNT (LLen, MLen, and HLen, respectively). Cells of bone marrow from adult BALB/L mice were cultured in DMEM medium with or without laminarin (inhibitor of dectin-1) to investigate the role of dectin-1 in the effect of lentinan on the expression profile of ß-catenin, Bcl-2, and Bax using western blotting and RT-PCR methods. The ELISA results indicated that the expression profiles of dectin-1 were significantly elevated in BMCs from groups of LLen, MLen, and HLen compared with the control group (P < 0.05). The protein and gene expression profiles of ß-catenin and Bax increased significantly in murine BMCs from groups of MLen and HLen compared with the control group or the LLen group (P < 0.05). In contrast, the protein and gene expression levels of Bcl-2 decreased significantly in BMCs from the LLen, MLen, and HLen groups compared with the control group (P < 0.05). Furthermore, the expression profiles of ß-catenin, Bcl-2, and Bax reversed with the administration of laminarin (P < 0.05). Taken together, our results identified that the changing expression profiles of ß-catenin, Bcl-2, and Bax in murine BMCs are associated with enhancing dectin-1.
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Células da Medula Óssea/efeitos dos fármacos , Lectinas Tipo C/genética , Lentinano/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteína X Associada a bcl-2/genética , beta Catenina/genética , Animais , Apoptose/efeitos dos fármacos , Feminino , Glucanos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos BALB CRESUMO
Escin, a triterpene saponin isolated from horse chestnut seed, has been used to treat encephaledema, tissue swelling and chronic venous insufficiency. Recent studies show that escin induces cell cycle arrest, tumor proliferation inhibition and tumor cell apoptosis. But the relationship between escin-induced DNA damage and cell apoptosis in tumor cells remains unclear. In this study, we investigated whether and how escin-induced DNA damage contributed to escin-induced apoptosis in human colorectal cancer cells. Escin (5-80 µg/mL) dose-dependently inhibited the cell viability and colony formation in HCT116 and HCT8 cells. Escin treatment induced DNA damage, leading to p-ATM and γH2AX upregulation. Meanwhile, escin treatment increased the expression of p62, an adaptor protein, which played a crucial role in controlling cell survival and tumorigenesis, and had a protective effect against escin-induced DNA damage: knockdown of p62 apparently enhanced escin-induced DNA damage, whereas overexpression of p62 reduced escin-induced DNA damage. In addition, escin treatment induced concentration- and time-dependent apoptosis. Similarly, knockdown of p62 significantly increased escin-induced apoptosis in vitro and produced en escin-like antitumor effect in vivo. Overexpression of p62 decreased the rate of apoptosis. Further studies revealed that the functions of p62 in escin-induced DNA damage were associated with escin-induced apoptosis, and p62 knockdown combined with the ATM inhibitor KU55933 augmented escin-induced DNA damage and further increased escin-induced apoptosis. In conclusion, our results demonstrate that p62 regulates ATM/γH2AX pathway-mediated escin-induced DNA damage and apoptosis.
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Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Dano ao DNA/efeitos dos fármacos , Escina/uso terapêutico , Proteína Sequestossoma-1/metabolismo , Animais , Antineoplásicos/farmacologia , Proteínas Mutadas de Ataxia Telangiectasia/genética , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Autofagia/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Regulação para Baixo , Escina/farmacologia , Feminino , Histonas/genética , Histonas/metabolismo , Humanos , Camundongos Nus , Proteína Sequestossoma-1/genética , Transdução de Sinais/efeitos dos fármacos , Regulação para CimaRESUMO
OBJECTIVE: To study the effect of rhubarb on neonatal rats with bronchopulmonary dysplasia (BPD) induced by hyperoxia. METHODS: A total of 64 rats (postnatal day 4) were randomly divided into four groups: air control, rhubarb control, hyperoxia model, and hyperoxia+rhubarb (n=16 each). The rats in the hyperoxia model and hyperoxia+rhubarb groups were exposed to hyperoxia (60% O2) to establish a BPD model. The rats in the rhubarb control and hyperoxia+rhubarb groups were given rhubarb extract suspension (600 mg/kg) by gavage daily. The pathological changes of lung tissue were evaluated by hematoxylin-eosin staining on postnatal days 14 and 21. The content of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) were measured by spectrophotometry. The mRNA and protein expression levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were determined by RT-PCR and Western blot respectively. RESULTS: The hyperoxia model group showed reduced alveolar number, increased alveolar volume, and simplified alveolar structure, which worsened over the time of exposure to hyperoxia. These pathological changes were significantly reduced in the hyperoxia+rhubarb group. On postnatal days 14 and 21, compared with the air control and rhubarb control groups, the hyperoxia model group had significantly reduced radical alveolar count (RAC), significantly reduced activity of SOD in the lung tissue, and significantly increased content of MDA and mRNA and protein expression levels of TNF-α and IL-6 (P<0.05). Compared with the hyperoxia model group, the hyperoxia+rhubarb group had significantly increased RAC, significantly increased activity of SOD in the lung tissue, and significantly reduced content of MDA and mRNA and protein expression levels of TNF-α and IL-6 (P<0.05). CONCLUSIONS: Rhubarb may play a protective role in rats with BPD induced by hyperoxia through inhibiting inflammatory response and oxidative stress.
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Displasia Broncopulmonar/prevenção & controle , Hiperóxia/complicações , Extratos Vegetais/uso terapêutico , Rheum , Animais , Animais Recém-Nascidos , Displasia Broncopulmonar/metabolismo , Displasia Broncopulmonar/patologia , Modelos Animais de Doenças , Pulmão/metabolismo , Pulmão/patologia , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/genéticaRESUMO
OBJECTIVE: To investigate the effects of Ningmitai Capsules (NMT) combined with doxycycline hydrochloride (DH) on chronic prostatitis induced by Ureaplasma urealyticum (Uu). METHODS: This randomized controlled trial included 240 male patients with Uuîpositive chronic prostatitis, treated orally with NMT at 4 capsules tid (n= 35), DH at 100 mg bid (n = 78), and NMT+DH at the corresponding doses (n = 127), respectively, all for 2 successive weeks. At 1 week after drug withdrawl, we conducted routine urine analysis, EPS examination, and drug sensitivity test of the cultured Uu. RESULTS: The positiveîtoînegative rate of Uu was significantly higher in the NMT+DH group than in the NMT and DH groups (89.0% ï¼»113/127ï¼½ vs 54.3% ï¼»19/35ï¼½ and 71.8% ï¼»56/78ï¼½, P< 0.05), so were the cure rate (25.2% vs 20.0% and 20.5%, P< 0.05) and total effectiveness rate (89.0% vs 54.3% and 71.8%, P< 0.05). CONCLUSIONS: The combination of Ningmitai Capsules and doxycycline hydrochloride is more effective than either Ningmitai Capsules or doxycycline hydrochloride used alone in the treatment of Uuîpositive chronic prostatitis.
Assuntos
Antibacterianos/uso terapêutico , Doxiciclina/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Prostatite/tratamento farmacológico , Infecções por Ureaplasma/tratamento farmacológico , Ureaplasma urealyticum , Cápsulas , Quimioterapia Adjuvante , Doença Crônica , Humanos , Masculino , Prostatite/microbiologia , Infecções por Ureaplasma/microbiologiaRESUMO
Objective To comparatively observe clinical efficacies of Fusidic Acid Cream (FAC) , Longzhu Ointment (LO) , and their combination of minocycline hydrochloride for treating facial acne vulgaris. Methods Totally 186 patients with acne vulgaris were randomly assigned to the FAC group (103 cases) and the LO group (83 cases). Each group was further divided into two subgroups ac- cording to the severity of acne: single treatment group and united treatment group. Patients with mild ac- ne vulgaris in the FAC group received FAC alone (39 cases) , and those with severe acne vulgaris in the FAC group received FAC and minocycline hydrochloride (64 cases). Patients with mild acne vulgaris in the LO group received LO alone (27 cases) , and those with severe acne vulgaris in the LO group received LO and minocycline hydrochloride. The therapeutic course for all was 4 weeks, with one return vis- it once per week. Grading of skin lesions was assessed by global acne grading system (GAGS). Clinical improvement was evaluated. Skin spots, red areas, and other data were statistically analyzed by VISIA skin analyzer. Results GAGS score was statistically different between before and after treatment in the FAC group and the LO group (P <0. 05). The total effective rate was 64. 1% (25)39) in single treatment group of the FAC group and 66. 7% (18/27) in single treatment group of the LO group, but with no statisti- cal difference between the two groups (Χ² =0. 09, P >0. 05). The total effective rate was 70. 3% (45/64) in united treatment group of the FAC group and 62. 5% (35/56) in united treatment group of the LO group, but with no statistical difference between the two groups (Χ² =0. 04, P >0. 05). Results of VISIA showed, compared with before treatment, statistical difference existed in red area of single treatment group of the FAC group and the LO group (P <0. 05). Statistical difference existed in ultraviolet rays, red area, sclererythrin of united treatment group of the FAC group and the LO group (P <0. 05). Conclusions FAC and LO could effectively control the inflammation of acne. LO had a rapid onset. Combined with minocy- cline hydrochloride, FAC could significantly reduce the secretion of fats, and LO could defense against ultraviolet more significantly.