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To investigate the mechanism of the treatment of hyperlipidemia rats induced by Huangqi San. The 40 male SD rats were randomly divided into normal group, model group, Huangqi San low and high dose group (1, 2 g·kg⻹), and positive lipitor group (2 mg·kg⻹). The normal group feeds on base feed, and other groups feed on high-fat feed. After 8 weeks, the hyperlipidemia model was successful. After intervention by drugs for 13 weeks, fasting blood glucose, total cholesterol, triglycerides and LDL cholesterol content of all rats were measured. The pathological changes of liver and skeletal muscle of rats were observed in rats. Real-time PCR and Western blot were used to detect the mRNA and protein expression levels of AMPK signaling pathway in the liver and skeletal muscles (AMPK, ACC, CPT1A, SREBP2, HMGCR). The degree of FPG, TC, TG and LDL-C were the highest in the model group, and the liver and skeletal muscle pathology were the most obvious. After intervention by Huangqi San and lipitor, a significant reduction in the blood sugar blood fat, liver, and skeletal muscle injury has improved significantly, except SREBF2 and HMGCR mRNA and protein expression of this enzyme is reduced, other AMPK pathway related mRNA and protein expression increased significantly. Huangqi San effect is superior to lipitor. Huangqi San may improve hyperlipidemia by regulating the AMPK signaling pathway, increasing the oxidation of fatty acids and inhibiting cholesterol synthesis.
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Medicamentos de Ervas Chinesas/farmacologia , Hiperlipidemias/tratamento farmacológico , Transdução de Sinais , Adenilato Quinase/metabolismo , Animais , Glicemia/análise , Colesterol/sangue , Fígado/patologia , Masculino , Músculo Esquelético/patologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Triglicerídeos/sangueRESUMO
An approach for molecular similarity/substructure searching based on structural hierarchy matching is proposed. In this approach, small molecules are divided into two categories, acyclic and cyclic forms. The latter are further divided into three structural hierarchies, namely, framework, complicated-, and mono-rings. During searching, the similarity coefficients of a structural query and each retrieved molecule are calculated using the hierarchy of the query as the reference. A total of 13,911 chemicals were involved in this work, from which the minimal cyclic and acyclic substructures are extracted, and further processed into fuzzy structural fingerprints. Subsequently, the fingerprints are used as the searching indices for molecular similarity or substructure searching. The tests show that this approach can give user options to choose between one-substructure and multi-substructure searching with sorted results. Moreover, this algorithm has the potential to be developed for molecular similarity searching and substructure analysis.
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Algoritmos , Bases de Dados de Compostos Químicos , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
Diamide insecticides are widely used in rice paddies and pose a potential threat to aquatic organisms. However, the risk research related to their application in major rice-producing areas is very limited, especially mesocosm research to simulate the impact on aquatic ecosystems of long-term exposure, as well as exposure analysis based on local models and local scenarios. To assess potential risks from a novel diamide insecticide (tetrachlorantraniliprole) to aquatic nontarget organisms in the field over long-term exposure, an outdoor mesocosm study was performed, and the environmental concentrations were predicted by the multimedia paddy-pond model (TOPRICE). The mesocosm experiment showed that tetrachlorantraniliprole mainly stayed in the aqueous phase after entering the water body. Although the chemical dissipated quickly in the aqueous phase (half-life of 0.79-1.5 days), it showed toxic effects on zooplankton communities. Cladocerans, represented by Simocephalus vetulus, were most sensitive to tetrachlorantraniliprole stress. Significant short-term toxicity to cladocerans occurred in all treatment groups, but all recovered within 8 weeks except for the highest concentration group (30.0 µg /L). Based on the ecological recovery results, 7.74 µg tetrachlorantraniliprole/L (nominal concentration, 10.0 µg /L) is suggested to be the no-observed-ecological-adverse-effect concentration (NOEAEC) for the zooplankton community. When this NOEAEC was compared with predicted environmental concentrations (PECs; the PECs in natural ponds simulated by the TOPRICE model for 148 application scheme combinations in major rice-producing areas), a relatively high risk of applying tetrachlorantraniliprole during the rice tillering stage was found. The present study makes a positive contribution to the hypothesis that the current Tier 1 approaches for global acute risk assessment have a sufficient protective effect for assessing the risk of tetrachlorantraniliprole to aquatic organisms. Also, the present results should help us to gain a fuller understanding of the ecological risk of diamide insecticides in aquatic ecosystems and their rational application schemes. Environ Toxicol Chem 2024;43:429-439. © 2023 SETAC.
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Inseticidas , Oryza , Poluentes Químicos da Água , Animais , Inseticidas/toxicidade , Ecossistema , Zooplâncton , Diamida/farmacologia , Organismos Aquáticos , Poluentes Químicos da Água/toxicidadeRESUMO
Erythroxylumaustroguangdongense (Erythroxylaceae), a new species from Guangdong Province, China, is described and illustrated. This new species is morphologically most similar to E.calyptratum, but is distinguished by the leathery leaf blade with fewer pairs of secondary veins and flowers borne on leafless nodes of the basal part of the current branch with much longer pedicels and sub-rectangular petal appendages. This is the second native species of Erythroxylum recorded from China.
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Two new 13,28-epoxy oleanane-type triterpenoids, namely heterogenoside E and F, were isolated from Lysimachia heterogenea Klatt, together with the eight known compounds: palmitic acid, ß-stigmasterol, kaempferol, quercetin, hyperin, isorhamnetin, isorhamnetin-3-O-galactopyranoside and anagallisin C. Heterogenoside F possesses acetoxyl groups at the unusual C-21 and C-22 positions of its oleanane skeleton. The cytotoxic activities of anagallisin C, heterogenoside E and F were weak.
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Antineoplásicos Fitogênicos/isolamento & purificação , Extratos Vegetais/isolamento & purificação , Primulaceae/química , Triterpenos/isolamento & purificação , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Concentração Inibidora 50 , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Triterpenos/química , Triterpenos/farmacologiaRESUMO
The orthogonal test and the supercritical carbon dioxide fluid extraction were used for optimizing the extraction of the essential oil from Plumeria rubra var. actifolia for the first time. Compared with the steam distillation, the optimal operation parameter of extraction was as follows: extraction pressure 25 MPa, extraction temperature 45 degrees C; separator I pressure 12 MPa, separator I temperature 55 degrees C; separator II pressure 6 MPa, separator II temperature 30 degrees C. Under this condition the yield of the essential oil was 5.8927%. The components were separated and identified by GC-MS. 53 components of Plumeria rubra var. actifolia measured by SFE method were identified and determined by normalization method. The main components were 1, 6, 10-dodecatrien-3-ol, 3, 7, 11-trimethyl, benzoic acid, 2-hydroxy-, phenylmethyl ester, 1, 2-benzenedicarboxylic acid, bis(2-methylpropyl) ester,etc.. 1, 2-Benzenedicarboxylic acid, bis (2-methylpropyl) este. took up 66.11% of the total amount, and there was much difference of the results from SD method.
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Apocynaceae/química , Cromatografia com Fluido Supercrítico/métodos , Flores/química , Óleos Voláteis/isolamento & purificação , Álcoois/análise , Álcoois/química , Dióxido de Carbono , Ésteres/análise , Ésteres/química , Cromatografia Gasosa-Espectrometria de Massas , Laos , Estrutura Molecular , Óleos Voláteis/química , Pressão , TemperaturaRESUMO
BACKGROUND: Bamboos, widely distributed in temperate and tropical Asia, Africa and America, refer to a group of special plants in Poaceae, Bambusoideae. China is rich in bamboo species. However, due to a long flowering cycle, the flowering habit and the flowering structure of many bamboo species are still not well understood. Here, we report a new bamboo species from Guangdong, China and an analysis of its interesting branch development in relation to flowering. RESULTS: This species is similar to G. stellatus, the type species, but differs in the characteristics of its lemma and palea, mid-culm branch complement, and culm-sheath ligules. The initial branches at a culm node do not apically develop flowering structures during a flowering episode; instead, these form on what appears to be specialized flowering branches. CONCLUSIONS: The results of morphological comparison support the recognition of Gelidocalamus fengkaiensis as a new species. And during a flowering episode, two branch types ('foliage branch' and 'flowering branch') can be distinguished in this species.
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Artabotrys pachypetalus sp. nov. is described from Guangdong, Guangxi, Guizhou, Hunan and Jiangxi in China. A detailed description, distribution data, along with a color plate and a line drawing are provided. In China, specimens representing this species were formerly misidentified as A. multiflorus or A. hongkongensis (= A. blumei). Artabotrys blumei typically has a single flower per inflorescence, whereas both Artabotrys pachypetalus and A. multiflorus have multiple flowers per inflorescence. In addition, A. pachypetalus is readily distinguished from A. multiflorus in having thicker and shorter petals, and connivent and somewhat trigonal or terete inner petal blades. Artabotrys pachypetalus is most similar to A. punctulatus because both have multi-flowered inflorescences and similar petal length, but A. pachypetalus differs in having cream petals in vivo, connivent inner petal blades, and a short, raised rim above the inner petal claw. Artabotrys multiflorus should be excluded from the flora of China because none of the Chinese specimens of Artabotrys collected so far fall within the variation of A. multiflorus.
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BACKGROUND AND AIM: Overexpression of the human epidermal growth factor receptor 2 (HER-2) protein has been detected in gastric cancer and has been associated with an unfavorable prognosis. We investigated the anti-cancer effects of anti-p185(HER-2) ricin A chain (RTA) immunotoxin, alone or in combination with 5-flurouracil on SGC7901-HER-2+ cells. METHODS: SGC7901-HER-2+ cells were obtained by transfecting SGC7901 cells with HER-2-pcDNA3.1. Anti-p185(HER-2)-RTA was prepared by chemical conjugation of anti-HER-2 monoclonal antibody (mAb) and RTA. The SGC7901-HER-2+ cells were incubated with RTA, anti-p185(HER-2)-RTA, and/or 5-flurouracil. The effects of drugs on cells were evaluated by MTT assay and Annexin V-fluorescein isothiocyanate and propidium iodide double staining flow cytometry. The expression of caspase-3, caspase-9, cyclooxygenase-2, and nuclear factor-kappaB/p65 were assayed by western blot. SGC7901-HER-2+ cells were transplanted into BALB/c nude mice to produce solid tumors in an attempt to study the immunotoxin activity in vivo. RESULTS: In vitro, anti-p185(HER-2)-RTA inhibited cell growth and induced apoptosis in SGC7901-HER-2+ cells. Anti-p185(HER-2)-RTA enhanced caspase-3 and caspase-9 activity, while downregulating the expression of cyclooxygenase-2 and nuclear factor-kappaB/p65. Its combination with 5-flurouracil further inhibited the growth of SGC7901-HER-2+ cells. In vivo, our data showed that anti-p185(HER-2)-RTA significantly inhibited the growth of SGC7901-HER-2+ cells-transplanted tumors. CONCLUSIONS: Anti-p185(HER-2)-RTA inhibits the growth of SGC7901-HER-2+ cells. The effect may be related to the activation of caspase-3 and caspase-9 and inhibition of cyclooxygenase-2 and nuclear factor-kappaB/p65. Anti-p185(HER-2)-RTA plus 5-FU enhance anti-cancer activity, suggesting useful clues for further study for the treatment of HER-2 positive gastric cancers.
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Anticorpos Monoclonais/imunologia , Imunotoxinas/farmacologia , Receptor ErbB-2/imunologia , Ricina/farmacologia , Neoplasias Gástricas/tratamento farmacológico , Animais , Antimetabólitos Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Caspase 9/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , Relação Dose-Resposta a Droga , Fluoruracila/farmacologia , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Receptor ErbB-2/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/patologia , Fatores de Tempo , Fator de Transcrição RelA/metabolismo , Transfecção , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: Smear cytology (SC) using endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is the established and traditional choice for diagnosing pancreatic lesions. Liquid-based cytology (LBC) is a novel alternative cytological method, however, the comparative diagnostic efficacy of LBC remains inconclusive. AIM: To examine the diagnostic efficacy of LBC and SC for pancreatic specimens obtained through EUS-FNA via a systematic review and meta-analysis. METHODS: A systematic literature search was performed using PubMed, EMBASE, the Cochrane Library, and Web of Science. The numbers of true positives, false positives, true negatives, and false negatives for each cytological test (LBC and CS) were extracted from the included studies. The pooled sensitivity and specificity and the area under the summary receiver operating characteristic curve (AUC) were calculated, and the AUC was compared by Tukey's multiple comparisons test. The quality of the included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies II tool. RESULTS: A total of 1656 patients in eight studies were included. The pooled sensitivity and specificity and the AUC for LBC were 0.76 (95%CI: 0.72-0.79), 1.00 (95%CI: 0.98-1.00), and 0.9174, respectively, for diagnosing pancreatic lesions. The pooled estimates for SC were as follows: Sensitivity, 0.68 (95%CI: 0.64-0.71); specificity, 0.99 (95%CI: 0.96-100.00); and AUC, 0.9714. Similarly, the corresponding values for LBC combined with SC were 0.87 (95%CI: 0.84-0.90), 0.99 (95%CI: 0.96-1.00), and 0.9894. Tukey's multiple comparisons test was used to compare the sensitivities and AUCs of the three diagnostic methods; statistically significant differences were found between the three methods, and LBC combined with SC was superior to both LBC (P < 0.05) and SC (P < 0.05). The pooled sensitivity and AUC did not change significantly in the sensitivity analysis. CONCLUSION: LBC may be sensitive than SC in the cytological diagnosis of pancreatic lesions, however, the superior diagnostic performance of their combination emphasizes their integrated usage in the clinical evaluation of pancreatic lesions.
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BACKGROUND: Pit pattern classification using magnifying chromoendoscopy is the established method for diagnosing colorectal lesions. The Japan Narrow-band-imaging (NBI) Expert Team (JNET) classification is a novel NBI magnifying endoscopic classification that focuses on the vessel, and surface patterns. AIM: To determine the diagnostic efficacy of each category of the JNET and Pit pattern classifications for colorectal lesions. METHODS: A systematic literature search was performed using PubMed, Embase, the Cochrane Library, and Web of Science databases. The pooled sensitivity, specificity, diagnostic odds ratio, and area under the summary receiver operating characteristic curve of each category of the JNET and Pit pattern classifications were calculated. RESULTS: A total of 19227 colorectal lesions in 31 studies were included. The diagnostic performance of the JNET classification was equivalent to the Pit pattern classification in each corresponding category. The pooled sensitivity, specificity, and area under the curve (AUC) for each category of the JNET classification were as follows: 0.73 (95%CI: 0.55-0.85), 0.99 (95%CI: 0.97-1.00), and 0.97 (95%CI: 0.95-0.98), respectively, for Type 1; 0.88 (95%CI: 0.78-0.94), 0.72 (95%CI: 0.64-0.79), and 0.84 (95%CI: 0.81-0.87), respectively, for Type 2A; 0.56 (95%CI: 0.47-0.64), 0.91 (95%CI: 0.79-0.96), and 0.72 (95%CI: 0.68-0.76), respectively, for Type 2B; 0.51 (95%CI: 0.42-0.61), 1.00 (95%CI: 1.00-1.00), and 0.90 (95%CI: 0.87-0.93), respectively, for Type 3. CONCLUSION: This meta-analysis suggests that the diagnostic efficacy of the JNET classification may be equivalent to that of the Pit pattern classification. However, due to its simpler and clearer clinical application, the JNET classification should be promoted for the classification of colorectal lesions, and to guide the treatment strategy.
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Pólipos do Colo , Neoplasias Colorretais , Colonoscopia , Neoplasias Colorretais/diagnóstico por imagem , Humanos , Japão , Imagem de Banda EstreitaRESUMO
BACKGROUND: Intestinal mucosal barrier dysfunction plays an important role in the pathogenesis of ulcerative colitis (UC). Recent studies have revealed that impaired autophagy is associated with intestinal mucosal dysfunction in the mucosa of colitis mice. Resveratrol exerts anti-inflammatory functions by regulating autophagy. AIM: To investigate the effect and mechanism of resveratrol on protecting the integrity of the intestinal mucosal barrier and anti-inflammation in dextran sulfate sodium (DSS)-induced ulcerative colitis mice. METHODS: Male C57BL/6 mice were divided into four groups: negative control group, DSS model group, DSS + resveratrol group, and DSS + 5-aminosalicylic acid group. The severity of colitis was assessed by the disease activity index, serum inflammatory cytokines were detected by enzyme-linked immunosorbent assay. Colon tissues were stained with haematoxylin and eosin, and mucosal damage was evaluated by mean histological score. The expression of occludin and ZO-1 in colon tissue was evaluated using immunohistochemical analysis. In addition, the expression of autophagy-related genes was determined using reverse transcription-polymerase chain reaction and Western-blot, and morphology of autophagy was observed by transmission electron microscopy. RESULTS: The resveratrol treatment group showed a 1.72-fold decrease in disease activity index scores and 1.42, 3.81, and 1.65-fold decrease in the production of the inflammatory cytokine tumor necrosis factor-α, interleukin-6 and interleukin-1ß, respectively, in DSS-induced colitis mice compared with DSS group (P < 0.05). The expressions of the tight junction proteins occludin and ZO-1 in DSS model group were decreased, and were increased in resveratrol-treated colitis group. Resveratrol also increased the levels of LC3B (by 1.39-fold compared with DSS group) and Beclin-1 (by 1.49-fold compared with DSS group) (P < 0.05), as well as the number of autophagosomes, which implies that the resveratrol may alleviate intestinal mucosal barrier dysfunction in DSS-induced UC mice by enhancing autophagy. CONCLUSION: Resveratrol treatment decreased the expression of inflammatory factors, increased the expression of tight junction proteins and alleviated UC intestinal mucosal barrier dysfunction; this effect may be achieved by enhancing autophagy in intestinal epithelial cells.
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Colite , Animais , Autofagia , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colo , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Mucosa Intestinal , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Resveratrol/farmacologiaRESUMO
BACKGROUND: Conventional Crohn's disease (CD) treatments are supportive rather than curative and have serious side effects. Adipose-derived mesenchymal stem cells (ADSCs) have been gradually applied to treat various diseases. The therapeutic effect and underlying mechanism of ADSCs on CD are still not clear. AIM: To investigate the effect of ADSC administration on CD and explore the potential mechanisms. METHODS: Wistar rats were administered with 2,4,6-trinitrobenzene sulfonic acid (TNBS) to establish a rat model of CD, followed by tail injections of green fluorescent protein (GFP)-modified ADSCs. Flow cytometry, qRT-PCR, and Western blot were used to detect changes in the Wnt signaling pathway, T cell subtypes, and their related cytokines. RESULTS: The isolated cells showed the characteristics of ADSCs, including spindle-shaped morphology, high expression of CD29, CD44, and CD90, low expression of CD34 and CD45, and osteogenic/adipogenic ability. ADSC therapy markedly reduced disease activity index and ameliorated colitis severity in the TNBS-induced rat model of CD. Furthermore, serum anti-sacchromyces cerevisiae antibody and p-anti-neutrophil cytoplasmic antibody levels were significantly reduced in ADSC-treated rats. Mechanistically, the GFP-ADSCs were colocalized with intestinal epithelial cells (IECs) in the CD rat model. GFP-ADSC delivery significantly antagonized TNBS-induced increased canonical Wnt pathway expression, decreased noncanonical Wnt signaling pathway expression, and increased apoptosis rates and protein level of cleaved caspase-3 in rats. In addition, ADSCs attenuated TNBS-induced abnormal inflammatory cytokine production, disturbed T cell subtypes, and their related markers in rats. CONCLUSION: Successfully isolated ADSCs show therapeutic effects in CD by regulating IEC proliferation, the Wnt signaling pathway, and T cell immunity.
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Tecido Adiposo , Colite , Células-Tronco Mesenquimais , Animais , Colite/induzido quimicamente , Colite/terapia , Células Epiteliais , Transplante de Células-Tronco Mesenquimais , Ratos , Ratos Wistar , Regeneração , Linfócitos T , Ácido Trinitrobenzenossulfônico/toxicidade , Via de Sinalização WntRESUMO
BACKGROUND: Gastric cancer (GC) is one of the most common and deadliest types of cancer worldwide due to its delayed diagnosis and high metastatic frequency, but its exact pathogenesis has not been fully elucidated. ETS homologous factor (EHF) is an important member of the ETS family and contributes to the pathogenesis of multiple malignant tumors. To date, whether EHF participates in the development of GC via the c-Met signaling pathway remains unclear. AIM: To investigate the role and mechanism of EHF in the occurrence and development of GC. METHODS: The expression of EHF mRNA in GC tissues and cell lines was measured by quantitative PCR. Western blotting was performed to determine the protein expression of EHF, c-Met, and its downstream signal molecules. The EHF expression in GC tissues was further detected by immunohistochemical staining. To investigate the role of EHF in GC oncogenesis, small interfering RNA (siRNA) against EHF was transfected into GC cells. The cell proliferation of GC cells was determined by Cell Counting Kit-8 and colony formation assays. Flow cytometry was performed following Annexin V/propidium iodide (PI) to identify apoptotic cells and PI staining to analyze the cell cycle. Cell migration and invasion were assessed by transwell assays. RESULTS: The data showed that EHF was upregulated in GC tissues and cell lines in which increased expression of c-Met was also observed. Silencing of EHF by siRNA reduced the proliferation of GC cells. Inhibition of EHF induced significant apoptosis and cell cycle arrest in GC cells. Cell migration and invasion were significantly inhibited. EHF silencing led to c-Met downregulation and further blocked the Ras/c-Raf/extracellular signal-related kinase 1/2 (Erk1/2) pathway. Additionally, phosphatase and tensin homolog was upregulated and glycogen synthase kinase 3 beta was deactivated. Moreover, inactivation of signal transducer and activator of transcription 3 was detected following EHF inhibition, leading to inhibition of the epithelial-to-mesenchymal transition (EMT). CONCLUSION: These results suggest that EHF plays a key role in cell proliferation, invasion, apoptosis, the cell cycle and EMT via the c-Met pathway. Therefore, EHF may serve as an antineoplastic target for the diagnosis and treatment of GC.
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Neoplasias Gástricas , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Humanos , Invasividade Neoplásica , Neoplasias Gástricas/genéticaRESUMO
BACKGROUND: Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase that is involved in various diseases, including cancers, metabolic diseases, and inflammation-associated diseases. However, the role of SIRT1 in ulcerative colitis (UC) is still confusing. AIM: To investigate the role of SIRT1 in intestinal epithelial cells (IECs) in UC and further explore the underlying mechanisms. METHODS: We developed a coculture model using macrophages and Caco-2 cells. After treatment with the SIRT1 activator SRT1720 or inhibitor nicotinamide (NAM), the expression of occludin and zona occludens 1 (ZO-1) was assessed by Western blot analysis. Annexin V-APC/7-AAD assays were performed to evaluate Caco-2 apoptosis. Dextran sodium sulfate (DSS)-induced colitis mice were exposed to SRT1720 or NAM for 7 d. Transferase-mediated dUTP nick-end labeling (TUNEL) assays were conducted to assess apoptosis in colon tissues. The expression levels of glucose-regulated protein 78 (GRP78), CCAAT/enhancer-binding protein homologous protein (CHOP), caspase-12, caspase-9, and caspase-3 in Caco-2 cells and the colon tissues of treated mice were examined by quantitative real-time PCR and Western blot. RESULTS: SRT1720 treatment increased the protein levels of occludin and ZO-1 and inhibited Caco-2 apoptosis, whereas NAM administration caused the opposite effects. DSS-induced colitis mice treated with SRT1720 had a lower disease activity index (P < 0.01), histological score (P < 0.001), inflammatory cytokine levels (P < 0.01), and apoptotic cell rate (P < 0.01), while exposure to NAM caused the opposite effects. Moreover, SIRT1 activation reduced the expression levels of GRP78, CHOP, cleaved caspase-12, cleaved caspase-9, and cleaved caspase-3 in Caco-2 cells and the colon tissues of treated mice. CONCLUSION: SIRT1 activation reduces apoptosis of IECs via the suppression of endoplasmic reticulum stress-mediated apoptosis-associated molecules CHOP and caspase-12. SIRT1 activation may be a potential therapeutic strategy for UC.
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Apoptose , Colite Ulcerativa/patologia , Estresse do Retículo Endoplasmático , Mucosa Intestinal/patologia , Sirtuína 1/metabolismo , Animais , Células CACO-2 , Caspase 12/metabolismo , Técnicas de Cocultura , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Chaperona BiP do Retículo Endoplasmático , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Feminino , Compostos Heterocíclicos de 4 ou mais Anéis/administração & dosagem , Humanos , Mucosa Intestinal/citologia , Macrófagos , Camundongos , Niacinamida/administração & dosagem , Sirtuína 1/antagonistas & inibidores , Fator de Transcrição CHOP/metabolismoRESUMO
Callicarpa nudiflora has been widely used in Li nationality medicine and treated burns and scalds in China. Our objective was to preliminarily elucidate healing effect and action mechanism of Callicarpa nudiflora water extract (CNE) on the scald wounds using an experimental rat mode. The second-degree scald wounds were induced by hot water on dorsal surface of Sprague-Dawley (SD) rats, and then they were randomly divided into 5 groups as follows: control (CON), Vaseline, Silver sulfadiazine (SSD), and Vaseline supplemented with 10% and 20% CNE groups. These ointments were employed locally once daily for 21 days. The macroscopic analysis showed CNE significantly accelerated the wound healing process and lowered the wound areas on days 15, 18, and 21 especially in 20% CNE group compared to CON group. Histopathological evaluation showed the mildly hypertrophic epidermis and the intact dermis in the 20% CNE-treated group were obviously distinguished from CON group on day 21. The CNE-treated groups had no obvious effect for TNF-α and IL-10 expressions on the second day and 14th day, while TGF-ß1 expression level was decreased on the 21th day and VEGF level was increased on the 7th day in the 20% CNE group. Furthermore, the expression level of Samd3 was strongly inhibited in 20% CNE group. These findings suggested that the CNE can enhance the wound healing and skin repair in deep second-degree scald rats and thus support its traditional use.
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In the present study, a novel pH-responsive amphiphilic copolymer, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)] conjugated poly(ß-amino esters) (DSPE-b-PEG-b-PAE-b-PEG-b-DSPE), was designed and successfully synthesized via Michael-type step polymerization. The chemical structure of the pentablock copolymer was confirmed with proton nuclear magnetic resonance (1H-NMR) and Fourier transform infrared (FT-IR) spectroscopy. The copolymer was able to self-assemble into core/shell polymeric micelles in aqueous solution at low concentrations, and its critical micelle concentration (CMC) value was 4.5 mg l-1 determined by fluorescence spectrophotometry. The pKb value of the copolymer was about 6.5, confirmed by acid-base titration, indicating the pH-sensitivity of the polymeric micelle. The hydrodynamic diameter, distribution and zeta potential of the polymeric micelles at different pH conditions were monitored by dynamic light scattering (DLS). Doxorubicin (DOX) was encapsulated into the core of the micelles with a high drug loading content (15.9%) and entrapment efficacy (60.4%). In vitro experiments demonstrated that the release behaviour of DOX from the DOX-loaded polymeric micelles (DOX-PMs) was pH-triggered. When the pH decreased from 7.4 to 5.0, the drug release rate was markedly accelerated. MTT assay showed that the copolymer had negligible cytotoxicity whereas the DOX-PMs displayed high toxicity for tumour cells such as B16F10, HepG2 and HeLa cell lines. The results demonstrated that these pH-sensitive polymeric micelles could be used as potential anti-cancer drug carriers for cancer chemotherapy with controlled release.
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Mesh migration and penetration into abdominal viscera rarely occur after laparoscopic inguinal hernia repair. We present the first case of mesh migration into the sigmoid colon identified as a colonic polyp at initial colonoscopic examination. The patient complained of mild abdominal distention in the lower abdomen over the previous year without changes in bowel habits or stool appearance and without weight loss. By complementary endoscopic ultrasonography, a cavity-like structure beneath the suspected polyp was further confirmed. Enhanced abdominal computed tomography merely revealed local bowel wall thickening and inflammation of the colosigmoid junction. The migrating mesh, which was lodged in the sigmoid colon and caused intra-abdominal adhesion in the lower abdominal cavity, was finally identified via exploratory surgery. The components of inflammatory granulation tissue around the mesh material were diagnosed based on histological examination of the surgical specimen after sigmoidectomy. In this patient, nonspecific endoscopic and imaging outcomes during clinical work-up led to the diagnostic dilemma of mesh migration. Therefore, the clinical, radiological and endoscopic challenges specific to this case as well as the underlying reasons for mesh migration are discussed in detail.
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RATIONALE: Intrauterine contraceptive devices (IUDs) are recommended as a means of contraception. Translocation of IUD is a rare and serious complication. Colonic inflammatory mass caused by translocated IUD initially misdiagnosed as a colonic polyp is extremely rare and has not been reported yet. PATIENT CONCERNS: This report presents a case of sigmoid colon translocation of intrauterine device on a 37-year-old female patient. Colonoscopy was performed due to her complain of repeated blood in stools and subsequently the patient was misdiagnosed as a sigmoid colon polyp. Nonetheless, the "polyp" was not able to be removed endoscopically. DIAGNOSES: Sigmoid colon translocation of an intrauterine device. INTERVENTIONS: To further clarify the diagnosis, computed tomography (CT) scan was performed and the "polyp" was confirmed to be caused by a translocated IUD. OUTCOMES: The translocated IUD was removed easily by surgery, and the patient recovered soon after the operation. LESSONS: The present case indicates that an annual gynaecologic examination is necessary to determine the position of the IUD, and a CT examination may help confirm an ectopic IUD.
Assuntos
Colite , Colo Sigmoide , Pólipos do Colo/diagnóstico , Colonoscopia/métodos , Erros de Diagnóstico , Migração de Dispositivo Intrauterino/efeitos adversos , Adulto , Colite/diagnóstico , Colite/etiologia , Colite/cirurgia , Colo Sigmoide/patologia , Colo Sigmoide/cirurgia , Remoção de Dispositivo/métodos , Diagnóstico Diferencial , Feminino , Humanos , Dispositivos Intrauterinos/efeitos adversos , Tomografia Computadorizada por Raios X/métodos , Resultado do TratamentoRESUMO
The histone acetyltransferases (HATs) adenovirus E1A-associated protein (p300) and CREB binding protein (CBP) serve as coactivators during a diverse assortment of cellular processes. In the present study, p300 and CBP were highly expressed in 5 gastric cancer (GC) cell lines (SGC7901, MKN45, MGC-803, BGC-823 and KATO III) compared with human normal gastric epithelial cell line (GES-1). C646, a selective inhibitor of p300 and CBP, inhibited cell viability and cell cycle and promoted cell apoptosis in all 5 GC cell lines. In addition, C646 suppressed the migration and invasion capability of the GC cell lines, except for the middle-differentiated SGC-7901 cell line. Furthermore, we detected the differential expression of corresponding oncogenic signalling molecules, such as c-Met, Akt, Bcl-2, Bax, cyclin D1, MMP7 and MMP9, in GC cells following C646 treatment. In conclusion, our results suggest that C646 inhibits the acetylation of histone H3 via inactivation of p300 and CBP, resulting in antineoplastic effects toward GC cells. Thus, the selective HAT inhibitor C646 could be a promising antitumour reagent for GC treatment.