RESUMO
OBJECTIVE: Falls are an important public health issue that poses a threat to the health of senior people and reduces their ability to maintain independence, which in turn reduces poor quality of life. Several studies have demonstrated a positive relationship between physical function and fall, it remains unclear whether there is an association between gait speed and fall-related injuries among the aging population, which represent the largest proportion of older adults in China. Therefore, the aim of this study was to examine the association between gait speed and fall-related injuries among older Chinese adults. METHODS: Data from the Global Ageing and Adult Health Survey (2007-2010) were analyzed. A stratified multi-stage cluster sampling design was used to collect the survey data. A total of 7558 Chinese adults aged 60 or older were included in this study. A 4-m walking test was used to assess gait speed. Fall-related injuries were self-reported by study participants. The binary logistic regression model was employed to examine the association between gait speed and fall-related injuries while controlling for age, sex, education years, smoking, alcohol consumption, and chronic diseases. RESULTS: The mean age of the sample of older Chinese adults was 69.70 ± 7.10 years (females accounted for 52.6%). The results showed that a normal gait speed was negatively correlated with fall-related injury (odds ratio = 1.20) when adjusting for all covariates. Moreover, a binary regression analysis showed that a normal gait speed was only negatively correlated with fall-related injury in male participants (odds ratio = 1.32). There were no significant results in rapid gait speed and fall-related injuries. CONCLUSION: The results suggest that a slow gait speed may predict a higher risk of fall-related injuries among older Chinese adults, especially older male adults. Further studies are needed to verify our findings.
Assuntos
Marcha , Velocidade de Caminhada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Qualidade de Vida , População do Leste Asiático , CaminhadaRESUMO
As a promising method for local tumor treatment, nanosecond pulsed electric field (nsPEF) ablation elicits a potent anti-tumor immune response. However, the mechanism of the nsPEF-mediated anti-tumor immune response and its effects on the tumor microenvironment remains unclear. Here, we demonstrated that nsPEF treatment increased the level of membrane PD-L1 in liver cancer cells. Furthermore, nsPEF induced the release of PD-L1-associated extra-cellular vesicles, leading to the dysfunction of CD8+ T cells, which could potentially be reversed by PD-L1 blockade. Biological and functional assays also demonstrated that nsPEF treatment resulted in the increased PD-L1 level and dysfunction of infiltrated CD8+ T cells in tumor tissues in vivo, indicating the long term antitumor efficacy of nsPEF treatment. A combination of nsPEF treatment and PD-L1 blockade effectively inhibited tumor growth and improved the survival of the tumor-bearing mouse. In conclusion, nsPEF treatment induced the translocation and release of PD-L1 and contributed to the dysfunction of infiltrated CD8+ T cells, resulting in tumor progression at later stages. The combination of nsPEF treatment and PD-L1 blockade is a promising therapeutic strategy for liver cancer.
Assuntos
Antígeno B7-H1/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Inibidores de Checkpoint Imunológico/administração & dosagem , Neoplasias Hepáticas/terapia , Animais , Linhagem Celular Tumoral , Terapia Combinada , Terapia por Estimulação Elétrica , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Neoplasias Hepáticas/metabolismo , Camundongos , Transporte Proteico , Resultado do Tratamento , Microambiente Tumoral , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: While the left sinus of Valsalva (LSV) is a frequent origin of ventricular arrhythmias (VAs). Uncommonly, VAs with right bundle branch block (RBBB) morphology may be successfully terminated from the LSV. OBJECTIVE: We aimed to investigate the electrocardiographic and electrophysiologic characteristics of VAs with RBBB which were successfully eliminated from the LSV. METHODS: We identified patients with VAs successfully ablated from the LSV from January 2014 to December 2017 and compared electrophysiologic characteristics and ablation sites of those VAs with RBBB versus a control group of patients with left bundle branch block morphology. RESULTS: We identified 18 patients with RBBB and predominant "R" waves in the precordial leads. In 12 (66.7%) patients, a small "s" wave in lead V2 and positive "R" in the remaining pericardial leads could be seen. Overall, a single "V" potential was seen in 72.2% of patients in the study group, while discrete potentials were recorded in 80% of the patients in the control group. The majority (88.9%) of the VAs could only be terminated at the nadir of the LSV in the study group. After mean follow-up of 33 ± 14 months, 93.8% and 92% were free of VAs after initial ablation in study and control group, respectively (P = 0.99). CONCLUSION: Some VAs with predominant monophasic "R" wave in precordial leads could be terminated from LSV, especially a small "s" wave in lead V2 was recorded. The nadir of LSV is highly successful for RBBB VAs and single electrogram was recorded at the target for most of the cases.
Assuntos
Bloqueio de Ramo/cirurgia , Ablação por Cateter , Eletrocardiografia , Técnicas Eletrofisiológicas Cardíacas , Frequência Cardíaca , Seio Aórtico/cirurgia , Taquicardia Ventricular/cirurgia , Complexos Ventriculares Prematuros/cirurgia , Potenciais de Ação , Adulto , Idoso , Bloqueio de Ramo/diagnóstico , Bloqueio de Ramo/fisiopatologia , Ablação por Cateter/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Seio Aórtico/fisiopatologia , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/fisiopatologia , Resultado do Tratamento , Complexos Ventriculares Prematuros/diagnóstico , Complexos Ventriculares Prematuros/fisiopatologia , Adulto JovemRESUMO
BACKGROUND AND AIM: Recurrence and metastasis are associated with poor prognosis in hepatocellular carcinoma even in the patients who have undergone radical resection. Therefore, effective treatment is urgently needed for improvement of patients' survival. Previously, we reported that nanosecond pulse electric fields (nsPEFs) can ablate melanoma by induction of apoptosis and inhibition of angiogenesis. This study aims to investigate the in vivo ablation strategy by comparing the dose effect of nanosecond electric fields in vitro and in vivo on hepatocellular carcinoma. MATERIALS AND METHODS: Four hepatocellular carcinoma cell lines HepG2, SMMC7721, Hep1-6, and HCCLM3 were pulsed to test the anti-proliferation and anti-migration ability of 100 ns nsPEFs in vitro. The animal model of human subdermal xenograft HCCLM3 cells into BALB/c nude mouse was used to test the anti-tumor growth and macrophage infiltration in vivo. RESULTS: In vitro assays showed anti-tumor effect of nsPEFs is dose-dependant. But the in vivo study showed the strategy of low dose and multiple treatments is superior to high dose single treatment. The macrophages infiltration significantly increased in the tumors which were treated by multiple low dose nsPEFs. CONCLUSION: The low dose multiple nsPEFs application is more efficient than high dose single treatment in inhibiting the tumor volume in vivo, which is quite different from the dose-effect relationship in vitro. Beside the electric field strength, the macrophage involvement must be considered to account for effect variability and toxicology in vivo.
Assuntos
Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/radioterapia , Terapia por Estimulação Elétrica/métodos , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/radioterapia , Ativação de Macrófagos/imunologia , Análise de Variância , Animais , Apoptose/efeitos da radiação , Linhagem Celular Tumoral , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neovascularização Patológica/radioterapiaRESUMO
BACKGROUND: Most patients after liver transplantation (LT) suffer from intestinal barrier dysfunction. Glycyl-glutamine (Gly-Gln) by parenteral supplementation is hydrolyzed to release glutamine, which improves intestinal barrier function in intestinal injury. This study aimed to investigate the effect of Gly-Gln by enteral supplementation on intestinal barrier function in rats after allogenetic LT under immunosuppressive therapy. METHODS: Twelve inbred Lewis rats were selected randomly as donors, and 24 inbred Brown Norway (BN) rats as recipients of allogenetic LT. The recipients were divided into a control group (Ala, n=12) and an experimental group (Gly-Gln, n=12). In each group, 6 normal BN rats were sampled for normal parameters on preoperative day 3. The 6 recipients in the control group received alanine (Ala) daily by gastric perfusion for 3 preoperative days and 7 postoperative days, and the 6 recipients in the experimental group were given Gly-Gln in the same manner. The 12 BN recipients underwent orthotopic LT under sterile conditions after a 3-day fast and were given immunosuppressive therapy for 7 days. They were harvested for sampling on postoperative day 8. The following parameters were assessed: intestinal mucosal protein content, mucosal ultrastructure, ileocecal sIgA content, portal plasma levels of endotoxin and TNF-alpha, and bacterial translocation. RESULTS: All recipients were alive after LT. On preoperative day 3, all parameters were similar in the two groups. On postoperative day 8, all parameters in the two groups were remarkably changed from those on preoperative day 3. However, compared to the Ala group, supplementation with Gly-Gln increased the levels of intestinal mucosal protein and ileocecal sIgA, improved mucosal microvilli, and decreased portal plasma levels of endotoxin and TNF-alpha as well as bacterial translocation. CONCLUSION: Enteral supplementation with Gly-Gln improved intestinal barrier function after allogenetic LT in rats.
Assuntos
Dipeptídeos/administração & dosagem , Nutrição Enteral , Íleo/efeitos dos fármacos , Absorção Intestinal/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Transplante de Fígado , Animais , Translocação Bacteriana/efeitos dos fármacos , Esquema de Medicação , Endotoxinas/sangue , Íleo/metabolismo , Íleo/ultraestrutura , Imunoglobulina A Secretora/metabolismo , Imunossupressores/administração & dosagem , Mucosa Intestinal/metabolismo , Mucosa Intestinal/ultraestrutura , Masculino , Permeabilidade , Ratos , Ratos Endogâmicos BN , Ratos Endogâmicos Lew , Fatores de Tempo , Fator de Necrose Tumoral alfa/sangueRESUMO
This study was designed to explore the mechanism of Huaier anticancer effects on experimental hepatocellular cancer (HCC) development. Seventy five rats were divided into 5 groups, administered N-nitrosodiethylamine (groups B, C, D and E) or natural saline (group A). Rats in group C and E were also given Huaier. At the 15 week sacrifice point, the HCC incidence of group C was lower than group correlating with serum AFP. The serum ALT concentration (98.9% greater) and P53 mRNA levels (23.2%) were higher in Group B than group C. Longer term survival rates between group D and E were not significantly different. Huaier can protect liver from chemical injury and furthermore HCC development, possibly with involvement of down-regulation of P53.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Fungos/química , Neoplasias Hepáticas Experimentais/prevenção & controle , Proteína Supressora de Tumor p53/metabolismo , Alanina Transaminase/sangue , Animais , Dietilnitrosamina , Regulação para Baixo/efeitos dos fármacos , Neoplasias Hepáticas Experimentais/induzido quimicamente , Neoplasias Hepáticas Experimentais/genética , Neoplasias Hepáticas Experimentais/metabolismo , Masculino , Medicina Tradicional Chinesa , RNA Mensageiro/genética , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Taxa de Sobrevida , Proteína Supressora de Tumor p53/genética , alfa-Fetoproteínas/metabolismoRESUMO
We aimed to assess the effects of traditional Chinese medicine; marine (MT) and kuhuang (KH), either alone or in combination, on the early graft function of the recipients and overall patient survival rate after liver transplantation (LT) by using diammonium glycyrrhizinate (DG) as a positive control. A total of 151 subjects undergoing LT were included in this prospective study. According to the different regimens given in the first two post-transplant weeks, they were divided into DG group (n = 49), DG + KH group (n = 36), MT group (n = 42) and MT + KH group (n = 24). The graft function in the early post-transplant period and patient survival rate were examined. During the first two post-transplant weeks, there was no significant difference in total bilirubin, alanine transaminase, aspartate transaminase, serum creatinine, and prothrombin time between MT group and DG group. Patient survivals in these two groups were also similar. Compared to DG group, DG + KH group showed a significantly lower total bilirubin value on post-transplant day 5 (3.2 +/- 2.1 mg/dL vs. 5.7 +/- 5.6 mg/dL, p < 0.01) and day 7 (2.8 +/- 1.8 mg/dL vs. 5.8 +/- 6.1 mg/dL, p < 0.01), and higher patient survival. There was no significant difference between DG + KH group and MT + KH group. In conclusion, MT provides an alternative to DG after LT. The combination of MT and KH is highly effective in decreasing the total blirubin in the early post-transplant period and improving patient survival.
Assuntos
Alcaloides/farmacologia , Bilirrubina/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Rim/efeitos dos fármacos , Transplante de Fígado/fisiologia , Fígado/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Quinolizinas/farmacologia , Adulto , Creatinina/sangue , Quimioterapia Combinada , Feminino , Ácido Glicirrízico/farmacologia , Humanos , Fígado/metabolismo , Transplante de Fígado/mortalidade , Magnoliopsida , Masculino , Pessoa de Meia-Idade , Fitoterapia , Estudos Prospectivos , Protrombina/metabolismo , Transferases/metabolismo , MatrinasRESUMO
Epidemiologic studies inclusively indicate that "unhealthy" dietary fat intake is one of the potential risk factors for cancer. In dietary fat, there are two types of polyunsaturated fatty acids (PUFA), omega-3 (n-3) and omega-6 (n-6). Numerous studies support that the ratio of n-6/n-3 affects tumorigenesis. It was reported that adenoviral transfer of the fat-1 gene, which converts n-6 to n-3, into breast and lung cancer cells had an antitumor effect in vitro. However, the effects of the fat-1 gene expression on tumor growth in vivo have not been studied and the mechanisms remain unclear. Accordingly, prostate cancer DU145 and PC3 cells were transfected with either the fat-1 gene or a control vector. The cells that expressed the fat-1 gene had a lower n-6/n-3 PUFA ratio compared with the cells that expressed the control vector. The fat-1 gene expression significantly inhibited prostate cancer cell proliferation and invasion in vitro. The fat-1 and control vector-transfected prostate cancer cells were s.c. implanted into severe combined immunodeficient mice for 6 weeks. The fat-1 gene expression significantly diminished tumor growth in vivo, but the control vector had no effect. Finally, we evaluated signaling pathways that may be important for fat-1 gene function. Administration of n-3 PUFA induced caspase-3-mediated prostate cancer cell apoptosis in vitro. The fat-1 gene expression inhibited prostate cancer cell proliferation via reduction of GSK-3beta phosphorylation and subsequent down-regulation of both beta-catenin and cyclin D1. These results suggest that fat-1 gene transfer directly into tumor cells could be used as a novel therapeutic approach.
Assuntos
Apoptose , Proteínas de Caenorhabditis elegans/genética , Ácidos Graxos Dessaturases/genética , Quinase 3 da Glicogênio Sintase/metabolismo , Neoplasias da Próstata/enzimologia , Neoplasias da Próstata/patologia , Animais , Apoptose/efeitos dos fármacos , Caenorhabditis elegans , Caspase 3/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ciclina D1/metabolismo , Regulação para Baixo/efeitos dos fármacos , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Ômega-6/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glicogênio Sintase Quinase 3 beta , Humanos , Masculino , Camundongos , Invasividade Neoplásica , Fosforilação/efeitos dos fármacos , Transfecção , beta Catenina/metabolismoRESUMO
AIM: To investigate the inhibitory effect of tea polyphenols (TP) on the transforming growth factor-beta1 (TGF-beta1) expression in rat model of cyclosporine A (CsA)-induced chronic nephrotoxicity. METHODS: The rat model of CsA-induced chronic nephrotoxicity was used, 4 groups of rats were respectively treated with vehicle (0.1 mL/kg/d sc), TP (80 mg/kg/d ig), CsA (15 mg/kg/d sc) and TP plus CsA (CsA 15 mg/kg/d sc+TP 80 mg/kg/d, ig). At the end of day 28 of treatment, serum and urine are analyzed for creatinine clearance, kidney tissue for pathologic analysis. The TGF-beta1 mRNA and its protein expression were detected by RT-PCR, immunohistochemistry, and Western blot. RESULTS: CsA-treated rats had increased renal expression of TGF-beta1 mRNA and its protein, compared with the vehicle- or TP-treated controls. The renal function and interstitial fibrosis were ameliorated and renal expression of TGF-beta1 mRNA and its protein was decreased in animals treated with CsA plus TP, compared with animals treated with CsA alone (P<0.05). CONCLUSION: TP significantly inhibits renal expression of TGF-beta1 in rat model of cyclosporine-induced chronic nephrotoxicity, suggesting that the decreased renal expression of TGF-beta1 exerted by TP is one of mechanisms to protect renal function and tissue structure.
Assuntos
Flavonoides/farmacologia , Nefropatias/metabolismo , Rim/metabolismo , Fenóis/farmacologia , Chá , Fator de Crescimento Transformador beta/biossíntese , Animais , Antioxidantes/farmacologia , Ciclosporina , Flavonoides/isolamento & purificação , Expressão Gênica , Nefropatias/induzido quimicamente , Masculino , Fenóis/isolamento & purificação , Polifenóis , RNA Mensageiro/genética , Ratos , Ratos Sprague-Dawley , Chá/química , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta1RESUMO
OBJECTIVE: To investigate the inhibitory effect of tea polyphenols on renal cell apoptosis in rat test subjects suffering from cyclosporine A (CsA)-induced chronic nephrotoxicity. METHODS: Four groups of rats with CsA-induced chronic nephrotoxicity were respectively treated with vehicle olive oil, tea polyphenols, CsA and tea polyphenols plus CsA. At the end of the 28th day of treatment, 24 hours urine and blood samples were obtained, and the animals were then sacrificed. The serum and urine samples were analysed for creatinine clearance, and kidney tissue was used for pathologic analysis of renal tubular injury and interstitial fibrosis. The TUNEL assay, apoptosis-related enzyme caspase-3 mRNA detected by RT-PCR, and its enzymatic activity were analysed for the possible detections of cell apoptosis. RESULTS: CsA-treated rats displayed increased apoptosis of the tubular and interstitial cells, in comparison with vehicle-treated controls (18.3 +/- 4.6 vs 4.8 +/- 1.3 cells/mm(2), P < 0.05). In comparison with animals treated by CsA, animals treated with CsA plus tea polyphenols demonstrated significantly improved levels of creatinine clearance (0.12 +/- 0.03 vs 0.22 +/- 0.02 ml.min(-1).100 g(-1) body weight, P < 0.05), tubular injury (2.29 +/- 0.43 vs 1.42 +/- 0.26, P < 0.05), and interstitial fibrosis (2.83 +/- 0.20 vs 1.46 +/- 0.19, P < 0.05), and showed a statistically significant decrease in tubular and interstitial cell apoptosis (18.3 +/- 4.6 vs 7.7 +/- 2.1 cells/mm(2), P < 0.05). The expression of caspase-3 mRNA and caspase-3 activity was significantly higher in the CsA-treated group than that of the CsA plus tea polyphenols (TP)-treated group (P < 0.05). CONCLUSION: These results suggested that tea polyphenols significantly inhibits apoptosis of the tubular and interstitial cells in rats with cyclosporine-induced chronic nephrotoxicity, and that tea polyphenols may be useful to prevent CsA-associated kidney toxicity.
Assuntos
Apoptose/efeitos dos fármacos , Ciclosporina/efeitos adversos , Flavonoides/farmacologia , Nefropatias/induzido quimicamente , Rim/patologia , Fenóis/farmacologia , Chá , Animais , Masculino , Polifenóis , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: To investigate the effect of tea polyphenols on cell apoptosis in rat model of cyclosporine-induced chronic nephrotoxicity. METHODS: Four groups of animals in rat model of cyclosporine-induced chronic nephrotoxicity were respectively treated by olive oil (n = 6), tea polyphenols (TP, n = 6), cyclosporine A (CsA, n = 8) and TP plus CsA (n = 8). At the end of 28th day of treatment, all animals were sacrificed and blood was analyzed for blood serum creatinine and creatinine clearance, kidney tissue for pathologic analysis. The TUNEL assay, caspase-3 mRNA expression detected by reverse transcription-polymerase chain reaction (RT-PCR) and caspase-3 activity were used for the analysis of cell apoptosis. RESULTS: CsA plus TP ameliorated the CsA-induced decrease of renal function and interstitial fibrosis. There was a significant increase in the number of apoptosis-positive cells in the CsA-vs-CsA plus TP-treated group at four weeks (18.9 +/- 3.3 vs. 7.7 +/- 1.4, P < 0.05). The expression of caspase-3 mRNA and caspase-3 activity of CsA-treated group was significantly higher than that of CsA plus TP-treated group (P < 0.05). CONCLUSION: These results indicate that antioxidant tea polyphenols significantly inhibit apoptosis of tubular and interstitial cells in rat model of chronic cyclosporine-induced nephrotoxicity, and suggest that the decrease of cell apoptosis exerted by tea polyphenols may be one of mechanisms to protect renal function and tissue structure.