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2.
Am J Surg ; 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33741185

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is common among adolescents and young adults (AYAs) in areas with endemic hepatitis B virus infection. We sought to characterize clinical features and long-term outcomes among AYAs versus older adults (OAs) who underwent HCC resection. METHODS: From a Chinese multicenter database, patients were categorized as AYA (aged 13-39 years) versus OA (aged ≥40 years). Patient clinical features, perioperative outcomes, overall survival (OS) and time-to-recurrence (TTR) were compared. Multivariable Cox-regression analyses were performed to identify the impact of age on OS and TTR. RESULTS: Among 1952 patients, 354(22.2%) were AYAs. AYAs were less likely to have cirrhosis yet were likely to have advanced tumor pathological characteristics than OAs. Postoperative morbidity and mortality were comparable. Compared with OAs, AYAs had a comparable OS but a decreased TTR. Multivariable analyses identified that young age (<40 years) was independently associated with poorer TTR. CONCLUSIONS: Compared with OAs, AYAs had a higher incidence of recurrence following liver resection among patients with HCC, suggesting that enhanced surveillance for postoperative recurrence may be required among AYAs.

3.
Medicine (Baltimore) ; 100(12): e24765, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33761638

RESUMO

ABSTRACT: MicroRNA (miR)-26a-5p is an oncogene significantly associated with osteosarcoma. We try to evaluate expression of circulating miR-26a-5p in osteosarcoma patients and evaluate its significance.A total of 243 consecutive osteosarcoma patients and 96 healthy participates were enrolled. Circulating miR-26a-5p levels were evaluated by using real-time quantitative reverse transcription polymerase chain reactions (RT-PCR). The association between circulating miR-26a-5p level and survival outcomes was evaluated by univariate and multivariate analysis.Circulating miR-26a-5p levels in osteosarcoma patients was significantly higher than that of healthy volunteers (P < .05). Upregulated miR-26a-5p was significantly related to advanced cancer and metastasis (both P < .05). Moreover, patients with a high serum miR-26a-5p had a poorer overall survival than those with a low serum miR-26a-5p levels (P < .05). Circulating miR-26a-5p level also been showed as independent risk factor for osteosarcoma in multivariate analysis (hazard ratio [HR], 0.38; 95% confidence interval [CI]: 0.11-0.98; P < .01).Circulating miR-26a-5p was significantly upregulated in osteosarcoma patients and remarkably associated with poor prognosis, indicating that circulating miR-26a-5p might serve as a useful diagnostic and prognostic biomarker for osteosarcoma.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Ósseas/mortalidade , MicroRNA Circulante/metabolismo , MicroRNAs/metabolismo , Recidiva Local de Neoplasia/epidemiologia , Osteossarcoma/mortalidade , Adulto , Biomarcadores Tumorais/sangue , Neoplasias Ósseas/sangue , Neoplasias Ósseas/genética , Neoplasias Ósseas/cirurgia , MicroRNA Circulante/sangue , Intervalo Livre de Doença , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Biópsia Líquida , Masculino , MicroRNAs/sangue , Recidiva Local de Neoplasia/genética , Osteossarcoma/sangue , Osteossarcoma/genética , Osteossarcoma/cirurgia , Estudos Retrospectivos , Medição de Risco/métodos , Regulação para Cima , Adulto Jovem
4.
Zhen Ci Yan Jiu ; 46(2): 123-8, 2021 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-33788433

RESUMO

OBJECTIVE: To observe the effect of warm needle with moxibustion (WNM) on morphological changes of articular cartilage and subchondral bone tissues in knee osteoarthritis (KOA) rabbits, so as to explore whether WNM intervention can delay the development of KOA. METHODS: Forty male New Zealand rabbits were randomly divided into blank control, model, WNM and medication (Alendronate sodium) groups, with 10 rabbits in each group. A KOA model was established by immobilizing the right hind limb of rabbits with orthopedic casting tape for 6 weeks. The rabbits of the WNM group received WNM stimulation at "Neixiyan"(EX-LE4) "Waixiyan"(ST35) and "Heding"(EX-LE2) for 15 min, once a day for 4 weeks and those of the medication group received gavage of Alendronate sodium (150 µg·kg-1·d-1) once a day for 4 weeks. X-ray examination and magnetic resonance imaging (MRI) scanning were performed to observe the structure of the knee joints. Outcomes of X-ray examination were used to assess the degree of bone hyperplasia and joint space stenosis which were scaled according to Kellgren and Lawrence (K-L) standards, and those of MRI used to evaluate the degree of cartilage damage and bone marrow edema degrees which were respectively scored according to Recht scaling standards and semi-quantitative whole-organ MRI score (WORMS). Histopathological changes (degeneration degrees) of the articular cartilage were observed after H.E. staining, and given Mankin score. The ultrastructure of the cartilage surface and chondrocytes was observed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM), respectively. RESULTS: Compared with the blank control group, the K-L grade, Recht grade, WORMS and Mankin score of the model group were significantly increased (P<0.05,P<0.01). After the intervention and in comparison with the model group, the K-L grade, Recht grade, WORMS and Mankin score of both WNM and medication groups were significantly decreased (P<0.05,P<0.01). Results of SEM showed severe defect, bulge and uneven surface of the cartilage with irregular growth and regeneration, and those of TEM showed degeneration and swelling of chondrocytes, margination of endonuclear chromatin, reduction in the number of organelles with disordered arrangement, extreme expansion of endoplasmic reticulum with detachment of the ribosome, unclear mitochondria, and disordered distribution of collagen fibers in the extracellular matrix in the model group, which was relatively milder in both the WNM and medication groups. Compared with the medication group, the Mankin score in the WNM group was evidently lower (P<0.05). CONCLUSION: WNM can effectively slow down the degeneration of cartilage and subchondral bone of KOA rabbits, delay the development of KOA.


Assuntos
Cartilagem Articular , Moxibustão , Osteoartrite do Joelho , Animais , Osso e Ossos , Articulação do Joelho , Masculino , Osteoartrite do Joelho/terapia , Coelhos
5.
Drug Dev Ind Pharm ; 45(3): 506-513, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30574810

RESUMO

BACKGROUND: Hand-foot-mouth disease may cause severe central nervous system complications and even death, that is induced mainly by enterovirus 71 (EV71), which is a non-enveloped virus. Inactivation of the EV71 on hands could effectively inhibit the transmission. However, the inactivations of the EV71 by conventional disinfectants including the alcohols are poor, due to the high stability of the EV71. A novel pyridyl imidazolidinone compound (TJAB1099) was designed to specifically inhibit EV71 replication in vitro. It may potentially be developed as formulations applied on hands for EV71 transmission control. METHODS: The stress stability of TJAB1099 was first evaluated after storing in high temperature (60 °C, RH 10%), high humidity (25 °C, RH90%), and the high-intensity photolysis (4500 Lx ± 500 Lx) for 15 days, respectively. A wash-free antimicrobial gel containing the TJAB1099 was developed using the copolymer carrier. The antiviral activity, the acute oral toxicity, and the local irritation of the antimicrobial gel were evaluated accordingly. RESULTS: The results indicated that the TJAB1099 was stable during the storage in high temperature and humidity. However, a significant change (p < .0001) was detected when TJAB1099 stored in the high-intensity photolysis. The antimicrobial gel containing 1 µM TJAB1099 could inhibit EV71 significantly higher than the ethanol (75%) (p < .0001) and commercialized disinfectant products (p < .0001). The results of acute oral toxicity and the local irritation suggest that the TJAB1099 containing antimicrobial gel was not causing skin irritations and acute oral toxicity symptoms. CONCLUSIONS: The results suggest that the antimicrobial gel containing TJAB1099 was safe and could effectively inhibit EV71 transmission in vitro.


Assuntos
Antivirais/farmacologia , Desinfetantes/farmacologia , Enterovirus/efeitos dos fármacos , Géis/farmacologia , Administração Tópica , Animais , Química Farmacêutica/métodos , Feminino , Doença de Mão, Pé e Boca/prevenção & controle , Masculino , Camundongos , Esterilização/métodos
6.
Curr Med Sci ; 38(5): 765-775, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30341511

RESUMO

A tissue engineering model of heart valve calcification induced in a bioreactor was established to evaluate the calcification induced by abnormal mechanical stimulation and explore the underlying molecular mechanisms. Polyethylene glycol (PEG)-modified decellularized porcine aortic leaflets seeded with human valve interstitial cells (huVICs) were mounted on a Ti-Ni alloy frame to fabricate two-leaflet and threeleaflet tissue engineered valves. The two-leaflet model valves were exposed to abnormal pulsatile flow stimulation with null (group A), low (1000 mL/min, group B), medium (2000 mL/min, group C), and high velocity (3000 mL/min, group D) for 14 days. Morphology and calcification were assessed by von Kossa staining, alkaline phosphatase (ALP) content, and Runx2 immunostaining. Leaflet calcification and mRNA and protein expression of transforming growth factor (TGF)-ß1, bone morphogenetic protein 2 (BMP2), Smad1, and MSX2 were measured at different time points. ALP content was examined in two-leaflet valves seeded with BMP2 shRNA plasmid-infected huVICs and exposed to the same stimulation conditions. The results showed that during 14 days of flow stimulation, huVICs on the leaflet surface proliferated to generate normal monolayer coverage in groups A, B, and C. Under mechanical stimulation, huVICs showed a parallel growth pattern in the direction of the fluid flow, but huVICs exhibited disordered growth in the high-velocity flow environment. von Kossa staining, ALP measurement, and immunohistochemical staining for Runx2 confirmed the lack of obvious calcification in group A and significant calcification in group D. Expression levels of TGF-ß1, BMP2, and MSX2 mRNA and protein were increased under fluid stimulation. ALP production by BMP2 shRNA plasmid-infected huVICs on model leaflets was significantly reduced. In conclusion, abnormal mechanical stimulation in a bioreactor induced calcification in the tissue engineering valve model. The extent of calcification correlated positively with the flow velocity, as did the mRNA and protein levels of TGF-ß1, BMP2, and MSX2. These findings indicate that TGF-ß1/BMP2 signaling is involved in valve calcification induced by abnormal mechanical stimulation.


Assuntos
Proteína Morfogenética Óssea 2/genética , Calcinose/genética , Doenças das Valvas Cardíacas/genética , Proteínas de Homeodomínio/genética , Fator de Crescimento Transformador beta1/genética , Idoso , Animais , Aorta/citologia , Aorta/transplante , Valva Aórtica/citologia , Valva Aórtica/transplante , Reatores Biológicos , Calcinose/fisiopatologia , Calcinose/terapia , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Feminino , Doenças das Valvas Cardíacas/fisiopatologia , Doenças das Valvas Cardíacas/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/química , Transdução de Sinais/genética , Proteína Smad1/genética , Suínos , Engenharia Tecidual
7.
Curr Med Sci ; 38(4): 691-696, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30128880

RESUMO

This study aims to evaluate the clinical outcomes of endoscopic vein harvesting (EVH) for coronary artery bypass grafting (CABG) in obese patients. Totally, 153 obese patients who underwent EVH (n=81) or standard bridging technique (SBT, n=12) in CABG surgery from May 2012 to October 2014 in our hospital were enrolled in this retrospective non-randomized controlled study. The general situation of operation, postoperative complications and short medium-term outcomes were analyzed. The baseline characteristics were similar between these two groups (P>0.05). There were no statistical differences in total operation time (226±28 min vs. 224±30 min, P>0.05), number of damaged vessels (0.12±0.05 vs. 0.16±0.06,P>0.05) and short medium-term outcomes including revascularization rate (1.25% vs. 2.78%, i 0.05), vessel dysfunction rate (11.25% vs. 11.11%,P>0.05) and mortality (0.00% v . 0.00%, P>0.05). Use of EVH was associated with significant reduction of total harvesting time (41 ±6 min vs. 63± 11 min, P<0.05), incision length (4.4±1.1 cm 18.2±4.5 cm, P<0.05) and postoperative lower extremity complications (P<0.05). EVH can reduce the risk of wound complications, whereas does not influence short- and medium-term outcomes in obese patients. It can be considered a reliable procedure of harvesting vessel conduits for obese patients undergoing CABG.


Assuntos
Ponte de Artéria Coronária/métodos , Endoscopia/métodos , Oclusão de Enxerto Vascular/epidemiologia , Obesidade/cirurgia , Complicações Pós-Operatórias/epidemiologia , Veia Safena/cirurgia , Coleta de Tecidos e Órgãos/métodos , Ponte de Artéria Coronária/efeitos adversos , Endoscopia/efeitos adversos , Feminino , Oclusão de Enxerto Vascular/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/complicações , Isquemia Miocárdica/cirurgia , Obesidade/complicações , Complicações Pós-Operatórias/etiologia , Coleta de Tecidos e Órgãos/efeitos adversos , Transplante Autólogo
8.
Am J Transl Res ; 10(4): 1117-1130, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29736205

RESUMO

The primary objective of this study was to investigate the role of miR-200a in cell proliferation and epithelial-mesenchymal transition (EMT) through regulating targeting aspartate-ß-hydroxylase (ASPH), which may further affect the activation of ERK/PI3K/Akt pathway. Liver cancer and adjacent tissues were collected from 72 cases of liver cancer patients with surgery in our hospital. In this study, the mRNA expression level of miR-200a was significantly decreased by real-time PCR (RT-PCR) detection. ASPH expressions, however, had an opposite tendency compared to that of miR-200a. We found a significantly negative correlation between miR-200a expressions and ASPH expressions. The survival rate of liver cancer patients with the low expressed ASPH was significantly higher than those with the high expressed ASPH. RT-PCR and Western blot results showed that low expressed miR-200a and highexpressed ASPH were found in liver cancer cell lines. Further research discovered that miR-200a transfection could significantly decrease the relative luciferase activity when it was integrated with ASPH 3'-untranslated region (3'-UTR) in HepG2 cells. Cell Counting Kit (CCK-8) detection showed that treatment with miR-200a mimics reduced cell viability, while the over-expressed ASPH increased cell viability by regulating the c-mycmrna (c-Myc) and Cyclin-D1 expressions. The EMT-related genes including E-Cadherin, N-Cadherin and Vimentin expressions were significantly increased, whereas the over-expressed ASPH exerted the opposite effects. In addition, extracellular signal regulated kinase (ERK), phosphoinositide-3-kinase (PI3K) and serine threonine kinase (AKT) were suppressed by miR-200a mimics. In conclusion, miR-200a inhibits cell proliferation and EMT in human hepatoma cells by targeting ASPH and affecting ERK and PI3K/Akt signaling pathways.

9.
Nan Fang Yi Ke Da Xue Xue Bao ; 37(9): 1201-1205, 2017 Sep 20.
Artigo em Chinês | MEDLINE | ID: mdl-28951362

RESUMO

OBJECTIVE: To evaluate the incidence of depression and anxiety caused by pegylated interferon α (PegIFN-α) treatment for chronic hepatitis B (CHB) and assess the efficacy of intervention with escitalopram and alprazolam. METHODS: A total of 165 CHB patients receiving PegIFN-α-based treatment for 12 weeks were assessed for moderate to severe depression and anxiety using Patient Health Questionnaire (PHQ-9) and 7-item Generalized Anxiety Disorder Scale (GAD-7)]. The patients identified to have moderate to severe depression and anxiety treated with escitalopram or alprazolam and the psychological condition of the patients was assessed at the 2nd, 4th and 8th weeks of the treatments. RESULTS: In the 165 patients receiving PegIFN-α treatment, 51 patients developed moderate to severe psychiatric symptoms, incuding 37 (22.4%) with depression, 31 (18.8%) with anxiety, and 17 (10.3%) with both. The symptoms of depression and anxiety was both significantly improved by intervention with escitalopram (P=0.000); alprazolam was effective for anxiety (P=0.001) but did not produce obvious effects on depression (P=0.904). Nevertheless, alprazolam had a much better therapeutic effect than escitalopram on anxiety in these patients (t=-3.198, P=0.010). CONCLUSION: Psychological symptoms are common in CHB patients receiving PegIFN-α treatment. The symptoms of depression and anxiety can be ameliorated by intervention with escitalopram and alprazolam, respectively.

10.
J Nat Prod ; 79(7): 1857-61, 2016 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-27400088

RESUMO

Two new phthalide derivatives, angesinenolides A and B (1 and 2), were isolated from the roots of Angelica sinensis. Their structures were elucidated using HRMS, NMR, and X-ray crystallographic data. Compound 1 is the first example of a phthalide trimer presumably formed through two [2+2] cycloaddition reactions. Compound 2 is a unique dimeric phthalide with a peroxy bridge between C-3a and C-6. Both phthalides were evaluated for in vitro anticoagulation activities. Compound 1 reduced the level of fibrinogen (FIB). Compound 2 significantly extended thrombin time and activated partial thromboplastin time, as well as markedly reduced the content of FIB.


Assuntos
Angelica sinensis/química , Anticoagulantes/isolamento & purificação , Benzofuranos/isolamento & purificação , Benzofuranos/farmacologia , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Anticoagulantes/química , Anticoagulantes/farmacologia , Benzofuranos/química , Cristalografia por Raios X , Medicamentos de Ervas Chinesas/química , Fibrinogênio/análise , Fibrinogênio/efeitos dos fármacos , Estrutura Molecular , Raízes de Plantas/química , Trombina/análise , Trombina/efeitos dos fármacos
11.
Nan Fang Yi Ke Da Xue Xue Bao ; 36(6): 775-9, 2016 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-27320877

RESUMO

OBJECTIVE: To evaluate the effect of long-term therapy with entecavir and Fufang Biejia Ruangan tablet in patients with chronic hepatitis B (CHB)-associated fibrosis and explore the synergistic therapy that accelerates the reversion of liver fibrosis. METHODS: A total of 197 patients with CHB-associated fibrosis were recruited from Nanfang Hospital between June, 2010 and June, 2015. The patients were divided into two groups after matching for age, gender and liver stiffness measurement (LSM), namely group A (n=98) treated with Fufang Biejia Ruangan Tablet plus entecavir, and group B (n=99) to receive entecavir only. HBV DNA quantification, HBV serological indicators, blood biochemical indexes, and results of abdominal ultrasound and FibroScan were recorded every 12 weeks. FibroScan values were converted to Metavir staging. RESULTS: Both groups showed significant decreases in serum levels of HBV DNA, alanine aminotransferase (ALT), and LSM value from baseline (all P<0.05). The median time to achieve Metavir fibrosis staging improvement were 72 weeks in group A and 96 weeks in group B (P<0.05), and the median time to achieve ALT and AST normalization were 12 and 24 weeks in Group A, respectively, significantly shorter than the time in group B (P<0.05). No significant difference was found between the two groups in HBV DNA undetectable rate and HBeAg seroconversion rate. CONCLUSION: The combination therapy with Fufang Biejia Ruangan tablet and entecavir produces a stronger efficacy than entecavir alone in the treatment of chronic hepatitis B patients with liver fibrosis, and Fufang Biejia Ruangan tablet shows an obvious hepatoprotective effect in these patients.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Guanina/análogos & derivados , Hepatite B Crônica/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Alanina Transaminase/sangue , DNA Viral/sangue , Guanina/uso terapêutico , Antígenos E da Hepatite B/sangue , Humanos , Comprimidos
12.
Zhongguo Zhong Yao Za Zhi ; 41(2): 167-176, 2016 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-28861958

RESUMO

Angelica sinensis(Umbelliferae)is a worldwide-known medicinal plant and also a famous traditional Chinese medicinal herb. It is recorded to possess the efficacy of enriching the blood and invigorating the circulation of blood of the individual.Danggui was extensively applied to the treatment of gynecological disorders. Modern researches indicate that phthalides are main chemical components related to the bioactivities of A.sinensis, such as anti-tumor, analgesic and neuroprotective effect.The advances in studies on the structures and pharmacological activities of phthalides from A.sinensis are reviewed to provide references for further researches and utilization of their medicinal value.


Assuntos
Angelica sinensis/química , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Animais , Tratamento Farmacológico , Humanos , Raízes de Plantas/química , Plantas Medicinais/química
13.
Ying Yong Sheng Tai Xue Bao ; 27(9): 2855-2863, 2016 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-29732848

RESUMO

Soil samples were collected from an alpine coniferous forest. Soil cores with soil organic layer above and mineral soil layer below were incubated in plant growth chambers during 10 weeks. Taking the annual average soil temperature in the alpine forest as the control, and other two levels of temperature were increased 2 and 4 ℃, respectively, to investigate the responses of soil microbial community and soil enzyme activity to warming. The results showed that warming significantly reduced PLFAs content of bacteria in soil organic layer and PLFAs content of G- in the mineral soil layer, whereas soil fungi was slightly influenced by warming. Warming caused the G+/G- increasing and changed the microbial community structure, but had no significant effect on soil enzymes activity, i.e., laccase (Lac), ß-1,4-glucoside (BG), acid phosphate (AP), ß-1,4-N-acetylglucosaminidase (NAG). There were significantly positive correlations between fungi, bacteria, G+ and G-, showing the coordinated growth trend between soil microbial communities. There was significantly negative correlation between BG and bacteria, showing the BG competing for carbon source utilization with soil microbial community. In consequence, the soil microbe types responded differently to warming. Bacteria were more sensitive to temperature than fungi, and fungi had stronger ability to tolerate warming in the alpine forest.


Assuntos
Florestas , Microbiologia do Solo , Temperatura , Bactérias , Mudança Climática , Enzimas/metabolismo , Fungos , Solo/química
14.
World J Gastroenterol ; 20(14): 4071-5, 2014 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-24744598

RESUMO

AIM: To evaluate the efficacy and tolerability of low-dose standard or pegylated interferon (PEG-IFN) in hepatitis C virus (HCV)-positive hemodialysis patients. METHODS: In total, 19 patients were enrolled in this study, of which 12 received PEG-IFNα-2a 67.5 µg 1 time/wk (Group 1) and 7 received standard interferon α-2b subcutaneously 1.5 × 106 U 3 times/wk (Group 2). The treatment durations were 48 wk for patients infected with HCV genotype 1 and 24 wk for patients infected with HCV genotype 2/3. All patients were prospectively followed after the completion of therapy. The efficacy and tolerability of the treatment were evaluated based on the sustained virological response (SVR) and treatment-related drop-out rate. RESULTS: In Group 1, 11 of the 12 patients completed the treatment. Early virological response (EVR) and sustained virological response (SVR) rates were 83.3% and 91.7%, respectively. One patient withdrew from treatment due to an adverse event (leukopenia). The drop-out rate was 8.3% in this group. In Group 2, 5 of the 7 patients completed the treatment with an EVR and SVR of 85.7% and 71.4%, respectively. Two patients withdrew due to treatment-related adverse events (nausea and depression). In this group, the drop-out rate was 28.6%. In total, 16 of the patients attained EVR, and 15 of them completed the treatment. The SVR rate for the patients who attained EVR was 93.7%. Anemia was the most frequent side effect and was observed in 10/19 patients (55.5%), but could be effectively managed with erythropoietin. CONCLUSION: Low-dose interferon monotherapy, either with PEG-IFNα-2a or standard interferon α-2b, is an effective treatment option for hemodialysis patients with chronic hepatitis C.


Assuntos
Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/administração & dosagem , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Diálise Renal/métodos , Adulto , Esquema de Medicação , Eritropoetina/uso terapêutico , Feminino , Genótipo , Hepacivirus , Humanos , Interferon alfa-2 , Interferon-alfa/uso terapêutico , Falência Renal Crônica/virologia , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/uso terapêutico , Estudos Prospectivos , Proteínas Recombinantes/uso terapêutico , Fatores de Tempo , Resultado do Tratamento
15.
Cancer Sci ; 105(4): 445-54, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24484175

RESUMO

Chemotherapy drugs themselves may act as stressors to induce adaptive responses to promote the chemoresistance of cancer cells. Our previous research showed that sirtuin 1 (SIRT1) was overexpressed in pancreatic cancer patients and deregulation of SIRT1 with RNAi could enhance chemosensitivity. Thus, we hypothesized that SIRT1 might facilitate chemoresistance in pancreatic cancer cells through regulating the adaptive response to chemotherapy-induced stress. In the present study, SIRT1 in PANC-1, BXPC-3, and ASPC-1 cells was upregulated after treatment with gemcitabine. Moreover, the decrease in SIRT1 activity with special inhibitor EX527 had a synergic effect on chemotherapy with gemcitabine in PANC-1 and ASPC-1 cell lines, which significantly promoted apoptosis, senescence, and G0 /G1 cycle arrest. Western blot results also showed that SIRT1, acetylated-p53, FOXO3a, and p21 were upregulated after combined treatment, whereas no obvious change was evident in total p53 protein. To further confirm the role of SIRT1 in clinical chemotherapy, SIRT1 was detected in eight pancreatic cancer tissues acquired by endoscopy ultrasonography guided fine needle aspiration biopsy before and after chemotherapy. Compared to before chemotherapy, SIRT1 was significantly increased after treatment with gemcitabine in six cases. Thus, our results indicated a special role for SIRT1 in the regulation of adaptive response to chemotherapy-induced stress, which is involved in chemoresistance. Moreover, it indicates that blocking SIRT1 activity with targeting drugs might be a novel strategy to reverse the chemoresistance of pancreatic cancer.


Assuntos
Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Sirtuína 1/biossíntese , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacologia , Fluoruracila/farmacologia , Proteína Forkhead Box O3 , Fatores de Transcrição Forkhead/biossíntese , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pancreáticas/patologia , Interferência de RNA , Sirtuína 1/genética , Proteína Supressora de Tumor p53/biossíntese , Proteínas rho de Ligação ao GTP/biossíntese
16.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 33(3): 376-9, 2013 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-23713254

RESUMO

OBJECTIVE: To observe the effects of acute immobilization stress on the mRNA expression of tyrosine kinase B (TrkB) in rats' hippocampus. METHODS: Eighteen SD rats were randomly divided into three groups, i.e., the normal control group, the model group, and the medication group, 6 in each group. The acute immobilization stress model was prepared in the model group using acute immobilization for 2 h. Ginsenoside Rb1 (40 mg/kg) was peritoneally injected to rats in the medication group 30 min before modeling, with the same procedure as those for rats in the model group. No treatment was performed to rats in the normal control group. The plasma adrenocorticotropic hormone (ACTH) and corticosterone (CORT) contents were detected using ELISA. The mRNA expression of TrkB in the rats' hippocampus was detected using real-time fluorescence quantitative RT-PCR. RESULTS: Before modeling there was no statistical difference of plasma CORT or ACTH concentrations among three groups (P >0.05). The plasma CORT and ACTH concentrations increased in the model group and the medication group more significantly after modeling than before modeling, showing statistical difference (P <0.05). Besides, they were obviously higher in the model group than in the normal control group (P <0.05). They were obviously higher in the medication group than in the model control group (P <0.05). Compared with the normal control group, the mRNA expression of TrkB significantly decreased in the model group (87.73 +/- 7.62 vs 50.65 +/- 5.19, P < 0.05), showing statistical difference. The mRNA expression of TrkB was significantly higher in the medication group (78.91 +/- 18.07) than in the model group, showing statistical difference (P <0.05). CONCLUSION: Pretreatment by ginsenoside Rb1 could increase the plasma CORT and ACTH concentrations, maintain the mRNA expression of TrkB, thus relieving injury induced by acute immobilization stress.


Assuntos
Ginsenosídeos/farmacologia , Hipocampo/metabolismo , Receptor trkB/metabolismo , Estresse Psicológico/metabolismo , Hormônio Adrenocorticotrópico/sangue , Animais , Corticosterona/sangue , Masculino , RNA Mensageiro/genética , Ratos , Ratos Sprague-Dawley , Receptor trkB/genética
17.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 33(12): 1696-700, 2013 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-24517072

RESUMO

OBJECTIVE: To investigate the effect of ginsenoside Rb1 on cerebral infarction volume as well as IL-1 beta in the brain tissue and sera of focal cerebral ischemia/reperfusion (I/R) injury model rats. METHODS: The I/R rat model was established by using thread according to Zea-Longa. SD rats were randomly divided into five groups, i.e., the sham-operation group, the model group, the low dose ginsenoside Rb1 (20 mg/kg) group, the medium dose ginsenoside Rb1 group (40 mg/kg), and the high dose ginsenoside Rb1 group (80 mg/kg), 12 in each group. Rats in the sham-operation group only received middle cerebral artery occlusion (MCAO) but without thread insertion. The MCAO model was prepared in the rest 4 groups, followed by MCAO2 h later. Ginsenoside Rb1 at each dose was peritoneally administrated to rats in corresponding groups immediately after cerebral ischemia. Equal volume of normal saline was administered to rats in the sham-operation group. Rats' cerebral infarction volume, integrals of neurologic defect degree, expression of IL-1 beta content in the brain tissue and sera were observed 24 h after 2-h cerebral I/R. RESULTS: In the model group, integrals of neurologic defect degree were improved (P < 0.01), IL-1 beta positive cells in the brain tissue increased and serum IL-1 beta content elevated (P < 0.05), when compared with the sham-operation group. In comparison of the model group, integrals of neurologic defect degree were lowered in the medium dose and high dose ginsenoside Rb1 groups (P < 0.05, P < 0.01). The cerebral infarction volume was all shrunken in each ginsenoside Rb1 group, IL-1 beta positive cells in the brain tissue decreased, and IL-1 beta content in serum reduced (P < 0.01, P < 0.05). Compared with the low dose ginsenoside Rb1 group, integrals of neurologic defect degree decreased, the cerebral infarction volume shrunken, and IL-1 beta content in serum reduced in the high dose ginsenoside Rb1 group (P < 0.01, P < 0.05). CONCLUSION: Ginsenoside Rb1 (20, 40, 80 mg/kg) might effectively release local cerebral ischemia by down-regulating the IL-1 beta expression.


Assuntos
Isquemia Encefálica/metabolismo , Ginsenosídeos/farmacologia , Interleucina-1beta/metabolismo , Traumatismo por Reperfusão/metabolismo , Animais , Encéfalo/metabolismo , Isquemia Encefálica/sangue , Ginsenosídeos/administração & dosagem , Masculino , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/sangue
18.
Mol Biol Rep ; 39(1): 277-83, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21559840

RESUMO

Ventricular assist devices may function as a bridge to recovery or heart transplantation, however, little is known about its mechanisms. This study examined the role of matrix metalloproteinases (MMP)-tissue inhibitors of metalloproteinases (TIMP) axis in the process of recovery after unloading in a rat ischemic-induce heart failure (HF) model. Myocardial infarction model was created with the coronary artery ligation. The infarcted rats hearts were unloaded by heterotopic cardiac transplantation (n=14). 2 weeks later, the function of normal and infarcted hearts with or without loading was evaluated by Langendorff perfusion model. The hearts were then harvested and prepared for the study of expression of MMPs and TIMPs. Developed pressure in the unloading group was higher than the loading group (P=0.0074). Unloading increased the ratio of TIMP-1-MMP-1(1.38±0.11 vs. 0.76±0.09, P<0.05), TIMP-2-MMP-2 (1.06±0.10 vs. 0.33±0.07, P<0.01), TIMP-3-MMP-9(1.07±0.08 vs. 0.59±0.06, P<0.05). Although MMP-1, 2, 9 were downregulated (P<0.01, 0.01, 0.05, respectively), TIMP-2 and TIMP-3 upregulated (P<0.01, 0.05, respectively), MMP-7 and TIMP-1 was not affected significantly. The infarcted cardiac function could be improved by unloading. It was attributed to downregulation of MMP-1, 2 and 9, and upregulation of TIMP-2 and -3, and furthermore, the ratio of TIMPs to MMPs was increased, which might be more sensitive than sole MMPs or TIMPs for the judgment of myocardial matrix homeostasis.


Assuntos
Regulação da Expressão Gênica/fisiologia , Transplante de Coração/fisiologia , Metaloproteinases da Matriz/metabolismo , Infarto do Miocárdio/cirurgia , Recuperação de Função Fisiológica/fisiologia , Inibidores Teciduais de Metaloproteinases/metabolismo , Transplante Heterotópico/fisiologia , Animais , Pressão Sanguínea , Western Blotting , Vasos Coronários/cirurgia , Ecocardiografia , Coração Auxiliar , Ligadura , Ratos , Reação em Cadeia da Polimerase Via Transcriptase Reversa
19.
J Zhejiang Univ Sci B ; 12(6): 460-7, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21634039

RESUMO

A rapid sample treatment procedure for the gas chromatography-tandem mass spectrometry (GC-MS) determination of 19-nortestosterone (19-NT) in animal tissues has been developed. In our optimized procedures, enzymatic hydrolysis with ß-glucuronidase from Escherichia coli was performed in an acetate buffer (pH 5.2, 0.2 mol/L). Next, the homogenate was mixed with methanol and heated at 60 °C for 15 min, then placed in an ice-bath at -18 °C for 2 h. After liquid-liquid extraction with n-hexane, the analytes were subjected to a normal-phase solid phase extraction (SPE) C18 cartridge for clean-up. The dried organic extracts were derivatized with heptafluorobutyric anhydride (HFBA), and then the products were injected into GC-MS. Using electron impact mass spectrometry (EI-MS) with positive chemical ionization (PCI), four diagnostic ions (m/z 666, 453, 318, and 306) were determined. A standard calibration curve over the concentration range of 1-20 ng/g was reached, with Y=467084X-68354 (R²=0.9997) for 19-NT, and the detection limit was 0.3 ng. When applied to spiked samples collected from bovine and ovine, the recoveries ranged from 63% to 101% with relative standard deviation (RSD) between 2.7% and 8.9%. The procedure is a highly efficient, sensitive, and more economical method which offers considerable potential to resolve cases of suspected nandrolone doping in husbandry animals.


Assuntos
Resíduos de Drogas/análise , Cromatografia Gasosa-Espectrometria de Massas/métodos , Carne/análise , Nandrolona/análise , Espectrometria de Massas em Tandem/métodos , Animais , Bovinos , Nandrolona/isolamento & purificação , Ovinos , Extração em Fase Sólida
20.
Mol Med Rep ; 4(4): 719-22, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21567089

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and is characterized by a high degree of malignancy and a low survival rate. Most HCCs express insulin-like growth factors and their receptors (IGF-IR), which mediate signaling, promote survival and invasion, and prevent apoptosis. Thus, they may be potential targets for the treatment of HCCs. In the present study, the potential therapeutic effect of Tyrphostin AG1024 in HCC was examined. After treatment with various concentrations of AG1024 (one selective inhibitor of IGF-IR), AG1024 not only dose-dependently inhibited the proliferation of HCC cells and induced apoptosis, but also markedly inhibited invasion ability. Expression of proteins detected by Western blot analysis revealed that AG1024 dose-dependently increased the expression of cytochrome C, while procaspase-3 and phospho-ERK were down-regulated. Thus, IGF-IR inhibition may be a promising novel approach to the treatment of HCC.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Receptor IGF Tipo 1/antagonistas & inibidores , Tirfostinas/uso terapêutico , Apoptose , Caspase 3/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Citocromos c/metabolismo , Regulação para Baixo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Fosforilação , Receptor IGF Tipo 1/metabolismo
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