T cell immunoglobulin- and mucin-domain-containing molecule 3 (TIM-3) has been established as a negative regulatory molecule and plays a critical role in inflammatory diseases such as rheumatoid arthritis, hepatitis B and C, and human immunodeficiency virus (HIV)-related inflammation. Recent studies have shown that chronic inflammation may greatly affect the pathogenesis of non-Hodgkin lymphomas (NHL). The aim of this study was to investigate whether polymorphisms in the TIM-3 gene were associated with susceptibility to non-NHL and HIV-related NHL. Three polymorphisms in TIM-3 gene (?1516G/T, ?574G/T, and +4259T/G) were identified by polymerase chain reaction-restriction fragment length polymorphism in 434 NHL patients, 62 HIV-related NHL cases, and 512 healthy controls. Results showed that the prevalence of ?574GT genotype and +4259TG genotype were significantly increased in the NHL cases than in controls (odds ratio (OR)?=?2.72, 95 % confidence interval (CI)?=?1.50–4.92, p?=?0.0006 and OR?=?2.59, 95 % CI?=?1.49–4.49, p?=?0.0005, respectively). The ?1516G/T polymorphism did not reveal significant difference between patients and healthy controls. When analyzing the TIM-3 polymorphisms in HIV-related NHL patients, data showed that HIV+ NHL patients had higher prevalence of ?574GT or +4259TG genotypes than those cases without HIV infection (OR?=?3.48, 95 % CI?=?1.67–7.28, p?=?0.0005 and OR?=?2.92, 95 % CI?=?1.42–6.01, p?=?0.0026, respectively). These results suggested polymorphisms in TIM-3 gene could be new risk factors for NHL as well as HIV-related NHL and suggested a possible role of the inflammatory factor in these diseases. 相似文献
The development of a new tuberculosis (TB) vaccine has become one of the main objectives of the scientific community. Protein antigens have been widely explored as subunit TB vaccines, however lipid antigens could be equally important to be used or included in such a vaccine. The aim of this study was to demonstrate the potential of a liposome formulation composed of an extract of lipids from Mycobacterium smegmatis (Ms) as a TB vaccine candidate. We evaluated the immunogenicity of this formulation as well as the cross reactive response against antigens from Mycobacterium tuberculosis (MTb) in BALB/c mice. We determined the anti-liposome IgG response in sera from TB patients and from healthy subjects who displayed a positive (PPD+) or negative (PPD-) tuberculin skin test. A significant increase in anti-liposome IgG (p<0.05) was detected in animals immunized with Bacille Calmette-Guérin (BCG) compared with all groups, and in the group immunized with liposomes from Ms (LMs) compared to animals immunized with either LMs adjuvanted with aluminium (LMs-A) or the negative control group (phosphate buffered saline, PBS) respectively. With respect to the cross reactive response against a cocktail of cell wall antigens (CWA) from MTb, significantly higher IgG levels were observed in animals immunized with BCG and LMs compared to negative controls and either, aluminium-adjuvanted liposomes (LMs-A) or montanide (LMs-M) (p<0.05). Furthermore, the anti-liposome IgG response was significantly superior in sera from pulmonary TB patients compared to PPD+ and PPD- healthy subjects (p<0.001) suggesting the expression of these antigens in vivo during active MTb infection. The results obtained provide some evidence for the potential use of liposomes containing total lipid extracts of Ms as a TB vaccine candidate.
Objective To establish an uric acid associated nephropathy (UAN) animal model and explore the mechanisms involved. Methods Eighteen (6-8 weeks old) male Sprague-Dawley rats weighed 200-220 g were randomly assigned into 2 groups: the control group (n=9), the uric acid associated nephropathy group (n=9). UAN rat model was established by oral administration of adenine (0.1g/kg) and potassium oxonate (1.5 g/kg) mixture daily for 3 weeks. After 3 weeks, the rats were sacrificed and blood and kidney samples were collected. Serum uric acid, creatinine and other biochemistry index were measured weekly. PAS and Masson staining were conducted to evaluate renal pathology and renal fibrosis. Serum activity of xanthine oxidase (XOD) was examined. Expression of p-EGFR and EGFR were detected by western blot and α-SMA expression was detected by immunohistochemical staining. Results After 3 weeks, the model group rats got 1.5 folds increased serum creatinine and significantly elevated serum uric acid. PAS and Masson staining showed that the UAN kidney developed glomerulosclerosis, tubulointerstitial damage and inflammatory cell infiltration. Serum activity of xanthine oxidase (XOD) was significantly upregulated in UAN group [(52.68±9.79) μmol/L vs (32.23±6.72) μmol/L, P<0.05]. Western blot showed that EGFR was activated and α-SMA expression increased remarkably in renal interstitial area of UAN rats. Conclusions The mixture of adenine and potassium oxonate can successfully establish UAN model. Phosphorylation of EGFR may mediate the activation of renal interstitial fibroblasts and accelerate the development and progression of UAN. 相似文献
Renal sympathetic nerves are involved in the reflective activation of the sympathetic nervous system in circulatory control. Catheter-based renal denervation (RDN) ameliorated treatment-resistant hypertension safely, but 10%–20% of treated patients are nonresponders to radiofrequency denervation. The purpose of this study was to investigate the safety and efficiency of cryoablation for sympathetic denervation in a swine model and to explore a new way of RDN.
Methods:
Seven swines randomly assigned to two groups: Renal cryoablation (CR) group and control group. The control group underwent renal angiogram only. The CR group underwent renal angiogram plus bilateral renal cryoablation. Renal angiograms via femoral were performed before denervation, after denervation and prior to the sacrifice to access the diameter of renal arterial and the pressure of aorta abdominalis. Euthanasia of the swine was performed on 28-day to access norepinephrine (NE) changes of the renal cortex and the changes of renal nerves.
Results:
Cryoablation did not induce severe complications at any time point. There was no significant change in diameter of renal artery. CR reduced systolic blood pressure (BP) from 145.50 ± 9.95 mmHg at baseline to 119.00 ± 14.09 mmHg. There was a slight but insignificant decrease in diastolic BP. The main nerve changes at 28-day consisted of necrosis with perineurial fibrosis at the site of CR exposure in conjunction with the nerve vacuolation. Compared with the control group, renal tissue NE of CR group decreased by 89.85%.
Conclusions:
Percutaneous catheter-based cryoablation of the renal artery is safe. CR could effectively reduce NE storing in the renal cortex, and the efficiency could be maintained 28-day at least. 相似文献
Prdx1 is an important member of peroxiredoxins (Prdxs) regulating various cellular signaling and differentiation. Prdx1 confers an aggressive survival phenotype of cancer cells and drug-resistance, yet its role in hilar cholangiocarcinoma is not fully investigated. In present study, we detected the expression profile of Prdx1 in 88 hilar cholangiocarcinoma by tissue arrays and immunohistochemistry. Prdx1 level was down-regulated by specific Prdx1-shRNA in vitro and the possible mechanism was investigated. Overexpression of Prdx1 was observed in 53 of 88 cases (60.2%). Prdx1 expression was significantly associated with tumor invasion, nodal metastasis, advanced disease stage. Down-regulation of Prdx1 inhibited cell proliferation and colony formation of QBC939 cells and reduced the level of SNAT1 expression. Patients with Prdx1 overexpression had a shorter disease-free survival and overall survival than those without Prdx1 expression. Multivariate analysis showed that Prdx1 was an independent prognostic factor for patients with hilar cholangiocarcinoma. The data indicate that Prdx1 may contribute to the development and progression of hilar cholangiocarcinoma, partially through regulating SNAT1 expression, and may be used as a biomarker in predicting the outcome of patients with hilar cholangiocarcinoma. 相似文献
Objective: Increased expression of tumor necrosis factor a (TNF-α) has emerged as an important inflammatory factor in osteoarthritis (OA) and other joint diseases. The study was performed to investigate whether the expression of TNF-α in human chondrocytes was regulated by miRNAs. Methods: MiRNA-130a and TNF-α expression in cartilage specimens was examined in patients with knee osteoarthritis, chondrocytes and osteoarthritis rat model. Chondrocytes were transfected with siRNAs as a gene silencing methods. Expression of genes and proteins were analyzed by real-time PCR and western blotting respectively. Results: Increased TNF-α and decreased miRNA-130a were observed in tissues from osteoarthritis patients. Moreover, we found a highly negitive correlation between miRNA-130a and TNF-α. Next, miRNA-130a loss-of-function increased the expression of TNF-α and promoted inflammation in chondrocytes. It was reasonable that miRNA-130a regulated a distinct underlying molecular and pathogenic mechanism of OA by forming a negative feedback loop with TNF-α. Furthermore, there were the abnormalities of bone metabolism in OA rat, which showed the miRNA-130a and TNF-α dysfunction that was one of important factors for the occurrence and development of OA. Conclusions: Our results indicated that miR-130a played an important role in regulating the expression of TNF-α in human chondrocytes and identified miR-130a as a novel therapeutic target in OA. 相似文献