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(1) Background: Diabetes is a common metabolic disease that seriously endangers human health. In the present study, we investigated the therapeutic effects of the active ingredient Eleutheroside B (EB) from the traditional Chinese medicine Eleutheroside on diabetes mellitus in a zebrafish model. Concomitant hepatic injury was also analysed, along with the study of possible molecular mechanisms using metabolomics technology. This work should provide some theoretical references for future experimental studies. (2) Methods: A zebrafish diabetes model was constructed by soaking in a 1.75% glucose solution and feeding a high-fat diet. The intervention drug groups were metformin (100 µgâmL-1) and EB (50, 100, and 150 µgâmL-1) via water-soluble exposure for 30 days. Glucose, TG, TC, LDL-C, and HDL-C were evaluated in different treatment groups. GLUT4 protein expression was also evaluated in each group, and liver injury was observed by HE staining. Metabolomics techniques were used to investigate the mechanism by which EB regulates endogenous markers and metabolic pathways during the development of diabetes. (3) Results: All EB treatment groups in diabetic zebrafish showed significantly reduced body mass index (BMI) and improved blood glucose and lipid profiles. EB was found to upregulate GLUT4 protein expression and ameliorate the liver injury caused by diabetes. Metabolomics studies showed that EB causes changes in the metabolic profile of diabetic zebrafish. These were related to the regulation of purine metabolism, cytochrome P450, caffeine metabolism, arginine and proline metabolism, the mTOR signalling pathway, insulin resistance, and glycerophospholipid metabolism. (4) Conclusions: EB has a hypoglycaemic effect in diabetic zebrafish as well as significantly improving disorders of glycolipid metabolism. The mechanism of action of EB may involve regulation of the mTOR signalling pathway, purine metabolism, caffeine metabolism, and glycerophospholipid metabolism.
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Diabetes Mellitus , Glucose , Glucosídeos , Fenilpropionatos , Humanos , Animais , Metabolismo dos Lipídeos , Peixe-Zebra , Cafeína , Transportador de Glucose Tipo 4 , Serina-Treonina Quinases TOR , GlicerofosfolipídeosRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Acanthopanax senticosus (Rupr. & Maxim.) Harms (AS), also known as Eleutherococcus senticosus (Rupr. & Maxim.) Maxim. or Siberian ginseng, has a rich history of use as an adaptogen, a substance believed to increase the body's resistance to stress, fatigue, and infectious diseases. As a traditional Chinese medicine, AS is popular for its cardioprotective effects which can protect the cardiovascular system from hazardous conditions. Doxorubicin (DOX), on the other hand, is a first-line chemotherapeutic agent against a variety of cancers, including breast cancer, lung cancer, gastric cancer, and leukemia, etc. Despite its effectiveness, the clinical use of DOX is limited by its side effects, the most serious of which is cardiotoxicity. Considering AS could be applied as an adjuvant to anticancer agents, the combination of AS and DOX might exert synergistic effects on certain malignancies with mitigated cardiotoxicity. Given this, it is necessary and meaningful to confirm whether AS would neutralize the DOX-induced cardiotoxicity and its underlying molecular mechanisms. AIM OF THE STUDY: This paper aims to validate the cardioprotective effects of AS against DOX-induced myocardial injury (MI) while deciphering the molecular mechanisms underlying such effects. MATERIALS AND METHODS: Firstly, the cardioprotective effects of AS against DOX-induced MI were confirmed both in vitro and in vivo. Secondly, serum pharmacochemistry and network pharmacology were orchestrated to explore the in vivo active compounds of AS and predict their ways of functioning in the treatment of DOX-induced MI. Finally, the predicted mechanisms were validated by Western blot analysis during in vivo experiments. RESULTS: The results demonstrated that AS possessed excellent antioxidative ability, and could alleviate the apoptosis of H9C2 cells and the damage to mitochondria induced by DOX. In vivo experiments indicated that AS could restore the conduction abnormalities and ameliorate histopathological changes according to the electrocardiogram and cardiac morphology. Meanwhile, it markedly downregulated the inflammatory factors (TNF-α, IL-6, and IL-1ß), decreased plasma ALT, AST, LDH, CK, CK-MB, and MDA levels, as well as increased SOD and GSH levels compared to the model group, which collectively substantiate the effectiveness of AS. Afterward, 14 compounds were identified from different batches of AS-dosed serum and selected for mechanism prediction through HPLC-HRMS analysis and network pharmacology. Consequently, the MAPKs and caspase cascade were confirmed as primary targets among which the interplay between the JNK/Caspase 3 feedback loop and the phosphorylation of ERK1/2 were highlighted. CONCLUSIONS: In conclusion, the integrated approach employed in this paper illuminated the molecular mechanism of AS against DOX-induced MI, whilst providing a valuable strategy to elucidate the therapeutic effects of complicated TCM systems more reliably and efficiently.
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Antineoplásicos , Eleutherococcus , Neoplasias , Humanos , Eleutherococcus/química , Cardiotoxicidade/tratamento farmacológico , Farmacologia em Rede , Doxorrubicina/farmacologia , Antineoplásicos/farmacologia , Neoplasias/tratamento farmacológico , Estresse Oxidativo , ApoptoseRESUMO
Shenzhu Erkang Syrup (SZEK) is a traditional Chinese medicine that improves spleen and stomach function, tonifying the Qi and activating the blood; however, its therapeutic effects in hematopoietic dysfunction and their underlying mechanism remain unexplored. In this study, mice were given cyclophosphamide (100 mg/kg) by intraperitoneal injections for three days to produce hematopoietic dysfunction model. We investigated the hematopoietic effect and mechanism of SZEK in mice with hematopoietic dysfunction via histopathological examination, flow cytometry, enzyme-linked immunosorbent assay, and Western blotting combined with intestinal flora and serum metabolomics analysis. In mice with hematopoietic dysfunction, SZEK (gavage, 0.3 mL/25 g) alleviated pathological damage to the bone marrow and spleen; increased the number of naïve cells (Lin-), hematopoietic stem cells (Lin-Sca-1+c-Kit+), long-term self-renewing hematopoietic stem cells (Lin-Sca-1+c-Kit+CD48-CD150+), B lymphocytes (CD45+CD19+), and macrophages (CD11b+F4/80+) in the bone marrow; and reduced inflammation. Preliminary intestinal flora and serum metabolome analyses indicated that the pro-hematopoietic mechanism of SZEK was associated with macrophage differentiation. Further validation revealed that SZEK promoted hematopoiesis by decreasing the number of M2 macrophages and inhibiting the secretion of negative hematopoietic regulatory factors in mice with hematopoietic dysfunction.
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Medula Óssea , Medicamentos de Ervas Chinesas , Células-Tronco Hematopoéticas , Camundongos , Animais , Hematopoese , Células da Medula Óssea , Macrófagos , Camundongos Endogâmicos C57BLRESUMO
A pilot-scale carbon fibers enhanced ecological floating beds (CF-EFBs) was constructed. Compared to EFBs without carbon fibers enhancement, CF-EFBs have the better removal of total inorganic nitrogen (TIN), total phosphorus (TP), and chemical oxygen demand (COD), the removal efficiencies were 3.19, 3.49, and 2.74 times higher than EFBs. Throughout the pilot test (under three different coverage rates), the concentrations of COD, TIN and TP of effluent were 18.11 ± 4.52 mgL-1, 1.95 ± 0.92 mgL-1 and 0.13 ± 0.08 mgL-1. Meanwhile, the average removal of TIN, TP and COD from tailwater was 0.96 gm-2d-1, 0.07 gm-2d-1 and 2.37 gm-2d-1 respectively. When the coverage was 30 %, the CF-EFBs had better nitrogen removal effectiveness (TIN purification ability of 1.49 gm-2d-1). The enrichment of denitrifying bacteria, such as Aridibacter, Nitrospira, Povalibacter, and Phaeodactylibacter increased denitrification efficiency. These results verified the feasibility of CF-EFBs in tailwater treatment at pilot-scale, which was of great significance for the practical application of CF-EFBs.
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Purificação da Água , Fibra de Carbono , Nitrogênio , Fósforo , Desnitrificação , Carbono , Reatores Biológicos , Eliminação de Resíduos LíquidosRESUMO
BACKGROUND: Alcohol abuse leads to alcoholic liver disease (ALD), for which no effective treatment is yet known. Gentiana Scabra Bge is a traditional Chinese medicine; its extract has a significant liver protection effect, but its effects on the mechanism of improving alcohol-induced toxicity remain unclear. Therefore, this study used cell and mouse models to investigate how Gentiana Scabra Bge extract (GSE) might affect the TLT4/NF-κB inflammation pathway in ALD. METHODS: In mice, we induced the alcoholic liver injury model by applying alcohol and induced the inflammatory cell model by lipopolysaccharide (LPS)-induced macrophages. Using an enzyme-linked immunosorbent assay (ELISA) kit, aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and interleukin 1ß (IL-1ß), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α) levels were measured in liver tissue; we also performed histological analysis of liver tissue sections to assess the hepatoprotective effect of GSE on alcohol. Using real-time fluorescence quantification, we determined the expression of toll-like receptor 4 (TLR4) and nuclear factor κB (NF-κB) mRNA levels; we used Western blotting to detect the expression of TLR4/NF-κB signaling pathway-related proteins. RESULTS: We demonstrate that GSE decreased AST and ALT activity, ameliorated liver dysfunction, decreased cytokine levels, and reduced LPS-induced cellular inflammation. In addition, GSE protected mouse liver cells from the inflammatory response by reducing alcohol-induced liver pathological damage and downregulating genes and proteins such as nuclear factors. CONCLUSIONS: GSE can attenuate liver injury in mice through the TLR4/NF-κB pathway by inhibiting the activation of nuclear factors.
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Gentiana , Hepatopatias Alcoólicas , Animais , Camundongos , Gentiana/química , Inflamação/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , Fígado/metabolismo , Hepatopatias Alcoólicas/tratamento farmacológico , Hepatopatias Alcoólicas/metabolismo , Hepatopatias Alcoólicas/prevenção & controle , NF-kappa B/efeitos dos fármacos , Receptor 4 Toll-Like/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêuticoRESUMO
Ecological floating bed coupled with microbial electrochemical system (ECOFB-MES) has great application potential in micro-polluted water remediation yet limited by low electron transfer efficiency on the microbial/electrode interface. Here, an innovative cathode-enhanced EOCFB-MES was constructed with nano-Fe3O4 modification and applied for in-situ remediation both at lab scale (6 L, 62-day operation) and demonstration scale (2300 m2, 1-year operation). The cathode-enhanced ECOFB-MES exhibited superior removal in TOC (81.43 ± 2.05%), TN (85.12% ± 1.46%) and TP (59.80 ± 2.27%), much better than those of original ECOFB-MES and anode-enhanced ECOFB-MES in the laboratory test. Meanwhile, cathode-enhanced ECOFB-MES boosted current output by 33% than that of original ECOFB-MES, which made a great contribution to the improvement of ectopic electronic compensation for pollutant decontamination. Notably, cathode-enhanced ECOFB-MES presented high efficiency, stability and durability in the demonstration test, and fulfilled the average concentration of COD (9.5 ± 2.81 mg/L), TN (1.00 ± 0.21 mg/L) and TP (0.10 ± 0.04 mg/L) of effluent water to meet the Grade III (GB 3838-2002) with stable operation stage. Based on the KOSIM calculation, the removal loads of cathode-enhanced ECOFB-MES in carbon, nitrogen and phosphorus could reach 37.14 g COD/(d·m2), 2.62 g TN/(d·m2) and 0.55 g TP/(d·m2), respectively. According to the analysis of microbial communities and functional genes, the cathode modified by Fe3O4 made a sensible enrichment in electroactive bacteria (EAB) and nitrogen-converting bacteria (NCB) as well as facilitated the functional genes expression in electron transfer and nitrogen metabolism, resulting in the synergistic removal of carbon in sediment and nitrite in water. This study provided a brandnew technique reference for in-situ remediation of surface water in practical application.
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Fósforo , Água , Fósforo/análise , Carbono , Eletrodos , Nitrogênio/análiseRESUMO
This study investigated the effect of butanol extract of AS (ASBUE) on atherosclerosis in apolipoprotein E-deficient (ApoE-/-) mice. The mice were administered ASBUE (390 or 130â mg/kg/day) or rosuvastatin (RSV) via oral gavage for eight weeks. In ApoE-/- mice, ASBUE suppressed the abnormal body weight gain and improved serum and liver biochemical indicators. ASBUE remarkably reduced the aortic plaque area, improved liver pathological conditions, and lipid metabolism abnormalities, and altered the intestinal microbiota structure in ApoE-/- mice. In the vascular tissue of ASBUE-treated mice, P-IKKß, P-NFκB, and P-IκBα levels tended to decrease, while IκB-α increased in high fat-diet-fed atherosclerotic mice. These findings demonstrated the anti-atherosclerotic potential of ASBUE, which is mediated by the interaction between the gut microbiota and lipid metabolism and regulated via the Nuclear Factor-kappa B (NF-κB) pathway. This work paves the groundwork for subsequent studies to develop innovative drugs to treat atherosclerosis.
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Aterosclerose , Eleutherococcus , Extratos Vegetais , Animais , Camundongos , Apolipoproteínas/genética , Apolipoproteínas E/genética , Aterosclerose/tratamento farmacológico , Butanóis , Dieta Hiperlipídica/efeitos adversos , Eleutherococcus/química , NF-kappa B/metabolismo , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêuticoRESUMO
In recent years, black ginseng, a new type of processed ginseng product, has attracted the attention of scholars globally. Ginsenoside and ginseng polysaccharide, the main active substances of black ginseng, have been shown to carry curative effects for many diseases. This article focuses on the mechanism of their action in anti-inflammatory response, which is mainly divided into three aspects: activation of immune cells to exert immune regulatory response; participation in inflammatory response-related pathways and regulation of the expression level of inflammatory factors; effect on the metabolic activity of intestinal flora. This study identifies active anti-inflammatory components and an action mechanism of black ginseng showing multi-component, multi-target, and multi-channel characteristics, providing ideas and a basis for a follow-up in-depth study of its specific mechanism.
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Ginsenosídeos , Panax , Anti-Inflamatórios/farmacologia , Ginsenosídeos/química , Ginsenosídeos/farmacologia , Panax/química , Extratos Vegetais/farmacologia , Polissacarídeos/farmacologiaRESUMO
Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumors with a low quality of life. Because traditional surgical treatment often causes large wounds and then affects the quality of life of patients, it is urgent to find new and efficient drugs with good safety for clinical treatment. This study aimed to identify potential anticancer drugs starting from the traditional Chinese medicine Salvia miltiorrhiza extract. Cryptotanshinone, a compound isolated from the Chinese herb Salvia miltiorrhiza, was found to significantly induce apoptosis and inhibit proliferation in OSCC. By electron microscopy, autophagosomes were found. Confocal fluorescence microscopy data showed that cryptotanshinone significantly induced autophagy in OSCC cells. Mechanistically, the western blot assay indicated that cryptotanshinone induced cell autophagy through the activation of the LC3 pathway, whereas the autophagy inhibitor 3-methyladenine attenuated these effects. Furthermore, we demonstrated that cryptotanshinone had a significant antitumor effect in a tumor xenograft model, and no damage to vital organs was observed. Our findings provide evidence that cryptotanshinone may be a novel therapeutic strategy for the treatment of OSCC.
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Antineoplásicos , Carcinoma de Células Pequenas , Medicamentos de Ervas Chinesas , Neoplasias Bucais , Humanos , Masculino , Adulto , Fenantrenos/uso terapêutico , Neoplasias Bucais/tratamento farmacológico , Autofagia , Antineoplásicos/farmacologia , Carcinoma de Células Pequenas/tratamento farmacológico , Qualidade de VidaRESUMO
OBJECTIVE: To explore whether casticin (CAS) suppresses stemness in cancer stem-like cells (CSLCs) obtained from human cervical cancer (CCSLCs) and the underlying mechanism. METHODS: Spheres from HeLa and CaSki cells were used as CCSLCs. DNA methyltransferase 1 (DNMT1) activity and mRNA levels, self-renewal capability (Nanog and Sox2), and cancer stem cell markers (CD133 and CD44), were detected by a colorimetric DNMT activity/inhibition assay kit, quantitative real-time reverse transcription-polymerase chain reaction, sphere and colony formation assays, and immunoblot, respectively. Knockdown and overexpression of DNMT1 by transfection with shRNA and cDNA, respectively, were performed to explore the mechanism for action of CAS (0, 10, 30, and 100 nmol/L). RESULTS: DNMT1 activity was increased in CCSLCs compared with HeLa and CaSki cells (P<0.05). In addition, HeLa-derived CCSLCs transfected with DNMT1 shRNA showed reduced sphere and colony formation abilities, and lower CD133, CD44, Nanog and Sox2 protein expressions (P<0.05). Conversely, overexpression of DNMT1 in HeLa cells exhibited the oppositive effects. Furthermore, CAS significantly reduced DNMT1 activity and transcription levels as well as stemness in HeLa-derived CCSLCs (P<0.05). Interestingly, DNMT1 knockdown enhanced the inhibitory effect of CAS on stemness. As expected, DNMT1 overexpression reversed the inhibitory effect of CAS on stemness in HeLa cells. CONCLUSION: CAS effectively inhibits stemness in CCSLCs through suppression of DNMT1 activation, suggesting that CAS acts as a promising preventive and therapeutic candidate in cervical cancer.
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Neoplasias do Colo do Útero , Feminino , Humanos , Linhagem Celular Tumoral , Células HeLa , Células-Tronco Neoplásicas/metabolismo , RNA Interferente Pequeno/metabolismo , Neoplasias do Colo do Útero/metabolismoRESUMO
Colitis-associated cancer (CAC) is a subtype of inflammatory bowel disease (IBD)-associated colorectal cancer. Huoxiang Zhengqi (HXZQ) is a classical Chinese herbal medicine and has been used to treat intestinal disorders, however, anti-CAC effects and underlying mechanisms of HXZQ have not been reported. An azoxymethane/dextran sulfate sodium-induced CAC mice model was used to investigate the anti-CAC effect of HXZQ. HXZQ significantly reduced colonic inflammation, suppressed the size and number of tumors, and reduced the levels of pro-inflammatory cytokines (interleukin [IL]-1α, IL-1ß, IL-6, IL-17A, IL-21, IL-23, granulocyte macrophage-colony stimulating factor, and tumor necrosis factor-α) and oxidative stress markers (reactive oxygen species and malondialdehyde), and increased the levels of anti-inflammatory cytokines (IL-10 and IL-27) in CAC mice. Intestinal microbiota and serum metabolomics analyses indicated that HXZQ altered the gut microbial composition and the abundance of 29 serum metabolites in CAC mice. Additionally, HXZQ activated the nuclear factor-erythroid factor 2-related factor 2 (Nrf2) signaling pathway and increased the levels of antioxidants such as catalase (CAT), heme oxygenase-1 (HO-1), NAD(P)H quinone oxidoreductases-1 (NQO-1), and superoxide dismutase-1 (SOD-1). HXZQ inhibited the activation of the nuclear factor kappa-B (NF-κB) signaling pathway and decreased the expression of NLR family pyrin domain containing 3 (NLRP3) by inhibiting the phosphorylation of inhibitor of nuclear factor kappa-B (IκB), inhibitor of nuclear factor kappa-B kinase (IKK), and NF-κB. In conclusion, HXZQ alleviated CAC in mice by modulating the intestinal microbiota and metabolism, activating Nrf2-mediated antioxidant response, and inhibiting NF-κB-mediated NLRP3 inflammasome activation against inflammation. The present data provide a reference for the use of HXZQ as a therapeutic or combination agent for clinical CAC treatment.
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Doxorubicin (DOX) is an effective antineoplastic drug; however, its clinical application is limited owing to the side effect of fatal heart dysfunction on its use. Panax ginseng glycoproteins have antioxidant, antiapoptotic, and anti-inflammatory properties. Thus, the aim of this study was to investigate the effects and possible action mechanisms of P. ginseng glycoproteins against DOX-induced cardiotoxicity. To this end, we used an in vitro model of DOX-treated H9C2 cells and an in vivo model of DOX-treated rats. We found that P. ginseng glycoproteins markedly increased H9C2 cell viability, decreased creatine kinase and lactate dehydrogenase levels, and improved histopathological and electrocardiogram changes in rats, protecting them from DOX-induced cardiotoxicity. Furthermore, P. ginseng glycoproteins significantly inhibited myocardial oxidative insult through adjusting the intracellular ROS, MDA, SOD, and GSH levels in vitro and in vivo. In conclusion, our data suggest that P. ginseng glycoproteins alleviated DOX-induced myocardial oxidative stress-related cardiotoxicity. This natural product could be developed as a new candidate for alleviating DOX-induced cardiotoxicity.
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Doxorrubicina/toxicidade , Glicoproteínas/farmacologia , Cardiopatias/induzido quimicamente , Cardiopatias/tratamento farmacológico , Miócitos Cardíacos/efeitos dos fármacos , Panax/química , Animais , Antibióticos Antineoplásicos/toxicidade , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Glicoproteínas/química , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Distribuição Aleatória , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: To observe the effect of moxibustion on postpartum urodynamics and recovery of pelvic floor function based on the pelvic floor muscle function training. METHODS: A total of 150 puerperal women were randomly divided into an observation group (75 cases, 15 cases dropped off) and a control group (75 cases, 15 cases dropped off). The control group was treated with pelvic floor muscle function training, twice a day. Based on the treatment in the control group, the observation group was treated with Baixiao moxibustion at Qihai (CV 6), Guanyuan (CV 4), Sanyinjiao (SP 6) and Zusanli (ST 36), twice a week. The treatment started on the 42nd day after delivery, totaling for 12 weeks. The urodynamic indexes (functional urethral length [FUL], stress leak point pressure [SLPP], maximum urethral closure pressure [MUCP], bladder compliance [BC], maximum urethral pressure [MUP], detrusor pressure at maximum urinary flow rate [Pdet Qmax]), the international consultation on incontinence questionnaire-urinary incontinence-short form (ICIQ-UI-SF) score and vaginal muscle voltage were observed before and after treatment. The prolapse rate of pelvic floor organ and normal rate of pelvic floor muscle strength of the two groups were recorded after treatment. RESULTS: Compared before treatment, the levels of FUL, MUCP, BC, Pdet Qmax and SLPP in the observation group after treatment were increased (P<0.05), while the FUL and SLPP in the control group after treatment were increased (P<0.05). After treatment, the levels of FUL, SLPP, MUCP and BC in the observation group were higher than those in the control group (P<0.05). Compared before treatment, the ICIQ-UI-SF scores in the two groups after treatment were decreased (P<0.01), and the vaginal muscle voltage was increased (P<0.01). After treatment, the ICIQ-UI-SF score in the observation group was lower than that in the control group (P<0.01), and the vaginal muscle voltage in the observation group was higher than that in the control group (P<0.01). The prolapse rate of pelvic floor organ was 6.7% (4/60) in the observation group, which was lower than 20.0% (12/60) in the control group (P<0.05). The normal rate of pelvic floor muscle strength in the observation group was 88.3% (53/60), which was higher than 65.0% (39/60) in the control group (P<0.05). CONCLUSION: The moxibustion combined with pelvic floor muscle function training could improve postpartum urodynamics and pelvic floor muscle strength.
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Moxibustão , Incontinência Urinária por Estresse , Terapia por Exercício , Feminino , Humanos , Diafragma da Pelve , Período Pós-Parto , UrodinâmicaRESUMO
The Wan-Nian-Qing prescription (WNQP), an herbal composite containing Ornithogalum caudatum, has been used in China for several years for cancer treatment. However, the mechanism of its pharmacological action against liver cancer is not clear. This study aimed to investigate the role of WNQP in inhibiting tumor growth in hepatocellular carcinoma model mice and determine its mechanism of action. We established HepG2- and SMMC-7721-xenografted tumor models in nude mice and BALB/c mice. The mice were administered WNQP for 2 weeks. The bodyweight of each mouse was monitored every day, and the tumor size was measured using vernier caliper before each round of WNQP administration. After the last dose, mice were sacrificed. The tumors were removed, lysed, and subjected to proteome profiling, enzyme-linked immunosorbent assay, and western blotting. The liver, spleen, and kidney were collected for histopathological examination. The effects of WNQP against liver cancer were first systematically confirmed in HepG2- and SMMC-7721-xenografted nude mice and BALB/c mice models. WNQP inhibited tumor growth, but failed to affect bodyweight and organ structures (liver and spleen), confirming that it was safe to use in mice. In BALB/c mice, WNQP regulated immune function, inferred from the modulation of immune-related cytokines such as interleukins, interferon, tumor necrosis factors, and chemokines. Further results confirmed that this regulation occurred via the regulatory effects of WNQP on Nrf2 signaling. WNQP can inhibit the growth of HepG2- and SMMC-7721-xenografted tumors in nude mice and BALB/c mice. This effect manifests at least partially through immunomodulation mediated apoptosis.
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PURPOSE: Docosahexaenoic acid (DHA) plays an essential role in brain, and its status is dependent on dietary intakes. School-aged children in rural China, who consume diets low in omega-3 polyunsaturated fatty acids, may benefit from DHA supplementation. Therefore, this trial was performed to examine the effect of 6-month DHA supplementation on executive functions (EFs) among healthy school-aged children in rural China. METHODS: A randomized, double-blind, placebo-controlled trial was conducted among 106 primary school children aged 7-12 years in rural China. Participants were randomized to receive either 300 mg/d DHA or placebo for 6 months. EFs including working memory and cognitive flexibility were evaluated at baseline, at 3 months and at 6 months, using Digit Span Backwards and Wisconsin card sorting test, respectively. Socio-demographic data were collected at baseline, and erythrocyte membrane fatty acids and serum neurotransmitters were measured at baseline and after 6-month intervention. RESULTS: Ninety-four children (88.7%) completed the study according to the protocol. Changes in erythrocyte membrane fatty acids indicated good compliance of the participants. There was no significant intervention effect on serum neurotransmitters. In two-factor ANCOVA, both groups showed a significant improvement in the Digit Span Backwards and the Wisconsin card sorting test from baseline to endpoint. However, no significant intervention effect was found on any EF scores. Linear regression analysis suggested no significant association between changes in erythrocyte DHA level with changes in any EF scores. CONCLUSIONS: Supplementation with 300 mg/d DHA for 6 months had no benefit on EFs including working memory and cognitive flexibility among healthy school-aged children. This trial was registered at clinicaltrials.gov as NCT02308930 on December 5, 2014.
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Ácidos Docosa-Hexaenoicos , Ácidos Graxos Ômega-3 , Criança , China , Suplementos Nutricionais , Método Duplo-Cego , Função Executiva , Humanos , Instituições AcadêmicasRESUMO
OBJECTIVE@#To observe the effect of moxibustion on postpartum urodynamics and recovery of pelvic floor function based on the pelvic floor muscle function training.@*METHODS@#A total of 150 puerperal women were randomly divided into an observation group (75 cases, 15 cases dropped off) and a control group (75 cases, 15 cases dropped off). The control group was treated with pelvic floor muscle function training, twice a day. Based on the treatment in the control group, the observation group was treated with @*RESULTS@#Compared before treatment, the levels of FUL, MUCP, BC, Pdet Qmax and SLPP in the observation group after treatment were increased (@*CONCLUSION@#The moxibustion combined with pelvic floor muscle function training could improve postpartum urodynamics and pelvic floor muscle strength.
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Feminino , Humanos , Terapia por Exercício , Moxibustão , Diafragma da Pelve , Período Pós-Parto , Incontinência Urinária por Estresse , UrodinâmicaRESUMO
Pollen wall consists of several complex layers which form elaborate species-specific patterns. In Arabidopsis, the transcription factor ABORTED MICROSPORE (AMS) is a master regulator of exine formation, and another transcription factor, TRANSPOSABLE ELEMENT SILENCING VIA AT-HOOK (TEK), specifies formation of the nexine layer. However, knowledge regarding the temporal regulatory roles of TEK in pollen wall development is limited. Here, TEK-GFP driven by the AMS promoter was prematurely expressed in the tapetal nuclei, leading to complete male sterility in the pAMS:TEK-GFP (pat) transgenic lines with the wild-type background. Cytological observations in the pat anthers showed impaired callose synthesis and aberrant exine patterning. CALLOSE SYNTHASE5 (CalS5) is required for callose synthesis, and expression of CalS5 in pat plants was significantly reduced. We demonstrated that TEK negatively regulates CalS5 expression after the tetrad stage in wild-type anthers and further discovered that premature TEK-GFP in pat directly represses CalS5 expression through histone modification. Our findings show that TEK flexibly mediates its different functions via different temporal regulation, revealing that the temporal regulation of TEK is essential for exine patterning. Moreover, the result that the repression of CalS5 by TEK after the tetrad stage coincides with the timing of callose wall dissolution suggests that tapetum utilizes temporal regulation of genes to stop callose wall synthesis, which, together with the activation of callase activity, achieves microspore release and pollen wall patterning.
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Proteínas de Arabidopsis/genética , Arabidopsis/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Pólen/fisiologia , Fatores de Transcrição/metabolismo , Arabidopsis/fisiologia , Proteínas de Arabidopsis/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Epigênese Genética , Regulação da Expressão Gênica de Plantas , Glucosiltransferases/metabolismo , Histonas/metabolismo , Metilação , Plantas Geneticamente Modificadas/fisiologia , Pólen/genética , Regiões Promotoras GenéticasRESUMO
Antibiotic resistance is becoming significantly prominent and urgent in clinical practice with the increasing and wide application of antibacterial drugs. However, developing and synthesizing new antimicrobial drugs is costly and time-consuming. Recently, researchers shifted their sights to traditional Chinese medicine (TCM). Here, we summarized the inhibitory mechanism of TCM herbs and their active ingredients on bacteria, discussed the regulatory mechanism of TCM on antibiotic-resistant bacteria, and revealed preclinical results of TCM herbs and their active components against antibiotic-resistant bacteria in mouse models. Those data suggest that TCM herbs and their effective constituents exhibit potential blockage ability on antibiotic-resistant bacteria, providing novel therapeutic ideas for reversing antibiotic resistance.
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Ginsenosides, the key components isolated from ginseng, have been extensively studied in antitumor treatment. Numerous studies have shown that ginsenosides have direct function in tumor cells through the induction of cancer cell apoptosis and the inhibition of cancer cell growth and enhance the antitumor immunity through the activation of cytotoxic T lymphocytes and natural killer cells. However, little is known about the function of ginsenosides on myeloid immunosuppressive cells including dendritic cells in tumor, tumor-associated macrophages, and myeloid-derived suppressor cells in the tumor microenvironments. Those myeloid immunosuppressive cells play important roles in promoting tumor angiogenesis, invasion, and metastasis. In the review, we summarize the regulatory functions of ginsenosides on myeloid immunosuppressive cells in tumor microenvironment, providing the novel therapeutic methods for clinical cancer treatment.
Assuntos
Ginsenosídeos/farmacologia , Imunossupressores/farmacologia , Células Mieloides/efeitos dos fármacos , Células Supressoras Mieloides/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos , Animais , Antineoplásicos/farmacologia , Humanos , Células Matadoras Naturais/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Neoplasias/terapia , Linfócitos T Citotóxicos/efeitos dos fármacosRESUMO
Ginsengs, has long been used as one medicinal herb in China for more than two thousand years. Many studies have shown that ginsengs have preventive and therapeutic roles for cancer, and play a good complementary role in cancer treatment. Ginsenosides, as most important constituents of ginseng, have been extensively investigated and emphasized in cancer chemoprevention and therapeutics. However, the functional mechanism of Ginsenosides on cancer is not well known. This review will focus on introducing the functional mechanisms of ginsenosides and their metabolites, which regulate signaling pathways related with tumor growth and metastasis. Ginsenosides inhibit tumor growth via upregulating tumor apoptosis, inducing tumor cell differentiation and targeting cancer stem cells. In addition, Ginsenosides regulate tumor microenvironment via suppressing tumor angiogenesis-related proteins and pathways. Structural modification of ginsenosides and their administration alone or combinations with other Chinese medicines or chemical medicines have recently been developed to be a new therapeutic strategy for cancer.