Connective tissue growth factor and cardiac fibrosis after myocardial infarction.

The temporal and spatial expression of transforming growth factor (TGF)-beta(1) and connective tissue growth factor (CTGF) was assessed in the left ventricle of a myocardial infarction (MI) model of injury with and without angiotensin-converting enzyme (ACE) inhibition. Coronary artery ligated rats were killed 1, 3, 7, 28, and 180 days after MI. TGF-beta(1), CTGF, and procollagen alpha1(I) mRNA were localized by in situ hybridization, and TGF-beta(1) and CTGF protein levels by immunohistochemistry. Collagen protein was measured using picrosirius red staining. In a separate group, rats were treated for 6 months with an ACE inhibitor. There were temporal and regional differences in the expression of TGF-beta(1), CTGF, and collagen after MI. Procollagen alpha1(I) mRNA expression increased in the border zone and scar peaking 1 week after MI, whereas collagen protein increased in all areas of the heart over the 180 days. Expression of TGF-beta(1) mRNA and protein showed major increases in the border zone and scar peaking 1 week after MI. The major increases in CTGF mRNA and protein occurred in the viable myocardium at 180 days after MI. Long-term ACE inhibition reduced left ventricular mass and decreased fibrosis in the viable myocardium, but had no effect on cardiac TGF-beta(1) or CTGF. TGF-beta(1) is involved in the initial, acute phase of inflammation and repair after MI, whereas CTGF is involved in the ongoing fibrosis of the heart. The antifibrotic benefits of captopril are not mediated through a reduction in CTGF.     

Preparation and characterization of magnetic microspheres for the purification of interferon alpha-2b

Magnetic agarose microspheres (MAMS), magnetic cellulose microspheres (MCMS), and magnetic poly(vinyl alcohol) microspheres (MPVAMS) were prepared by various different preparation methods. MCMS coupled with anti-IFN alpha-2b monoclonal antibodies (mAb) were selected for the purification of interferon alpha-2b (IFN alpha-2b) after performance characterization among microspheres. Parameters of immunomagnetic separation (IMS), including binding mAb, elution behavior, and sample pretreatment conditions, were optimized to improve the purification efficiency of the separation of IFN alpha-2b by MCMS. Size-exclusion HPLC (HPSEC) showed that the IFN alpha-2b was purified from crude cell lysate had an overall purity of 92.9%, while immunological and biological assays showed an activity recovery of 88.5% and specific antiviral activity of 2.7 x 10(8) IU/mg. Identity and molecular mass of purified IFN alpha-2b were confirmed by western blot and matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS) analysis. This study illustrated the favorable separation media which combined desired properties for the development of magnetic separation of biological materials.     

Nitrate increases cisplatin chemosensitivity of oral squamous cell carcinoma via REDD1/AKT signaling pathway

Although cisplatin is one of the chemotherapeutics most frequently used in oral squamous cell carcinoma (OSCC) treatment,it exerts multiple side effects and poo...     

Role of angiotensin II and oxidative stress on renal aquaporins expression in hypernatremic rats

The aim of this study was to assess whether endogenous Ang II and oxidative stress produced by acute hypertonic sodium overload may regulate the expression of aquaporin-1 (AQP-1) and aquaporin-2 (AQP-2) in the kidney. Groups of anesthetized male Sprague–Dawley rats were infused with isotonic saline solution (control) or with hypertonic saline solution (Na group, 1 M NaCl), either alone or with losartan (10 mg kg^?1) or tempol (0.5 mg min^?1 kg^?1) during 2 h. Renal function parameters were measured. Groups of unanesthetized animals were injected intraperitoneally with hypertonic saline solution, with or without free access to water intake, Na+W, and Na?W, respectively. The expression of AQP-1, AQP-2, Ang II, eNOS, and NF-kB were evaluated in the kidney by Western blot and immunohistochemistry. AQP-2 distribution was assessed by immunofluorescence. Na group showed increased natriuresis and diuresis, and Ang II and NF-kB expression, but decreased eNOS expression. Losartan or tempol enhanced further the diuresis, and AQP-2 and eNOS expression, as well as decreased Ang II and NF-kB expression. Confocal immunofluorescence imaging revealed labeling of AQP-2 in the apical plasma membrane with less labeling in the intracellular vesicles than the apical membrane in kidney medullary collecting duct principal cells both in C and Na groups. Importantly, our data also show that losartan and tempol induces a predominantly accumulation of AQP-2 in intracellular vesicles. In unanesthetized rats, Na+W group presented increased diuresis, natriuresis, and AQP-2 expression (112?±?25 vs 64?±?16; *p?<?0.05). Water deprivation increased plasma sodium and diuresis but decreased AQP-2 (46?±?22 vs 112?±?25; §p?<?0.05) and eNOS expression in the kidney. This study is a novel demonstration that renal endogenous Ang II–oxidative stress, induced in vivo in hypernatremic rats by an acute sodium overload, regulates AQP-2 expression.     

二氮嗪对自发性高血压大鼠心功能及心肌ERK和JNK表达的影响

目的:探讨二氮嗪对离体自发性高血压大鼠心脏缺血/再灌注心功能及心肌组织ERK和JNK表达的影响及可能机制。方法:雄性自发性高血压大鼠取心行Langendorff灌流。实验分为5组(n=6/组):对照组(Con)在平衡后继续灌流40min,全心缺血25min,复灌30min。其余各组除全心缺血前处理不同外,余均同对照组。缺血预处理组(IP)2次给予5min缺血+10min复灌,二氮嗪预处理组(DP)给予2次含50μmol·L-1二氮嗪的K-H液10min后给不含二氮嗪的K-H液5min,5-HD、5-HD+DP组则在平衡后给予10min150μmol·L-1线粒体KATP阻断剂5-HD,余同Con及DP组。结果:IP组及DP组复灌末左室发展压、+dP/dtmax和-dP/dtmax的恢复率均高于Con组(P<0.01),但两组左室舒张末期压恢复率低于Con组(P<0.01);5-HD能拮抗二氮嗪引起的心功能指标的改善。复灌末IP、DP及5-HD+DP组ERK表达增加。IP组及DP组心肌的JNK表达低于Con组(P<0.05),5-HD+DP组JNK表达显著高于DP组。结论:二氮嗪预处理对离体自发性高血压大鼠心肌缺血/再灌注损伤有保护作用,此保护作用可能与ERK的表达增加及JNK表达减少有关。