Oxidative stress induced necroptosis activation is involved in the pathogenesis of hyperoxic acute lung injury.

Necroptosis has been found to be involved in the pathogenesis of some lung diseases, but its role in hyperoxic acute lung injury (HALI) is still unclear. This study aimed to investigate contribution of necroptosis to the pathogenesis of HALI induced by hyperbaric hyperoxia exposure in a rat model. Rats were divided into control group, HALI group, Nec-1 (necroptosis inhibitor) group and edaravone group. Rats were exposed to pure oxygen at 250 kPa for 6 h to induce HALI. At 30 min before hyperoxia exposure, rats were intraperitoneally injected with Nec-1 or edaravone, and sacrificed at 24 h after hyperoxia exposure. Lung injury was evaluated by histology, lung water to dry ratio (W/D) and bronchoalveolar lavage fluid (BALF) biochemistry; the serum and plasma oxidative stress, expression of RIP1, RIP3 and MLKL, and interaction between RIP1 and RIP3 were determined. Results showed hyperoxia exposure significantly caused damage to lung and increased necroptotic cells and the expression of RIP1, RIP3 and MLKL. Edaravone pre-treatment not only inhibited the oxidative stress in HALI, but also reduced necroptotic cells, decreased the expression of RIP1, RIP3 and MLKL and improved lung pathology. Nec-1 pretreatment inhibited necroptosis and improved lung pathology, but had little influence on oxidative stress. This study suggests hyperoxia exposure induces oxidative stress may activate necroptosis, involving in the pathology of HALI, and strategies targeting necroptosis may become promising treatments for HALI.

Research on the effect and mechanism of the CXCR-4-overexpressing BMSCs combined with SDF-1α for the cure of acute SCI in rats.

OBJECTIVE: To evaluate the effect and mechanism of bone marrow stem cells (BMSCs) modified with CXCR-4 gene combined with stromal derived factor-1α (SDF-1α) in the treatment of acute spinal cord injury (SCI) in rats. MATERIALS AND METHODS: CXCR-4 gene was transfected by a virus. Spinal cord injury rats were randomly divided into four groups: control group, SDF-1α group, CXCR-4/BMSC group and combined group. The motor function was evaluated with Blood Brain Barrier (BBB) score and the RNA expression of CXCR-4 were measured by PCR. Apoptosis of spinal cord was measured by TUNEL kit (Hu Bei, China). The protein level of Bcl-2 and Bax were measured by Western-blot. The BBB scores, mRNA CXCR-4 expression, and apoptosis rate were compared between four groups at 1d, 3d, 7d, 14d, 21d after the operation. RESULTS: The exercise ability in combined group restored in early and late periods of SCI. The apoptosis rates in the combined group are less than other three groups; the difference was statistically significant (p < 0.05). Bcl-2 in combined group is higher than the other 3 groups and Bax is less than the other 3 groups, the difference is statistically significant (p < 0.05). CONCLUSIONS: The neurological function of rats with a spinal cord can be improved by BMSCs modified with CXCR-4 combined with SDF-1α. The main mechanism may improve the expression of SDF-1α and decrease the apoptosis of the spinal cord.

Protein binding by the 3' untranslated region of alpha-striated tropomyosin.

Tropomyosin is a component protein of the thin filament system in striated muscle, regulating the interaction between actin and myosin. The 3' untranslated region of the alpha-striated tropomyosin gene (TM UTR) induces muscle differentiation when expressed in primary fibroblasts, but the mechanism has not been defined. We hypothesize that fibroblasts utilize resident proteins to effect this response, perhaps by TM UTR binding to protein(s). In order to facilitate identification of protein(s) involved in mediating this differentiation response, we investigated the potential for this sequence to bind to cellular protein utilizing electrophoretic mobility gel shifting analysis (EMSA) with and without UV cross-linking. Under very specific conditions (including pH, KCl, and Mg concentration and extent of phosphorylation of protein), the TM UTR is able to bind protein in cells that differentiate upon TM UTR expression. Protein binding is significantly more extensive in cytoplasmic than nuclear protein preparations. Secondary structure of the RNA probe facilitates protein binding. The molecular masses of bound proteins are approximately 42 and 115 kDa under basal conditions. EMSA analysis of extract from cultured skeletal muscle confirms that protein binding by the TM UTR occurs in this cell type, and is more extensive in less differentiated cells. The demonstration of highly regulated protein binding by the TM UTR raises the possibility that this sequence may cause differentiation by binding to endogenous proteins, and further that this sequence may play a role in normal differentiation. Identification of proteins bound by the TM UTR will be necessary to completely define the mechanism by which it causes differentiation.

Clinical patterns of diarrhea in AIDS. A retrospective study at the Federal University Hospital, Rio de Janeiro.

Three hundred and fifty two medical records of AIDS inpatients were analysed in a retrospective study to establish the frequency, clinical patterns and etiology of AIDS-related diarrhea. Diarrhea was observed in 58.8% of the patients, being a chronic symptom in 65.7%, and the first complaint in 24.6%. The most common cause of diarrhea was coccidea and the etiology remained unknown in 56.1% of the patients. Routine stool examination was the most sensitive method in the diagnosis of diarrhea. In countries with limited resources, the use of stool examinations seems to provide appropriate clinical management. The implementation of an objective protocol could improve the etiologic diagnosis of AIDS-related diarrhea without the burden of more complex and invasive technologies.

[The expression of Quox-1 gene homologous sequence in the development of early human embryos].

By using the b2 fragment of Quox-1 gene as probe, we have confirmed that the Quox-1 gene homologous sequence exists in the human genome according to the results of Southern blot. Studies on the expression of Quox-1 homologous sequence in early human embryos from 26 to 37 days by means of immunohistochemistry technigue with Quox-1 protein antibodies showed the spatiotemporal expression patterns: in 26 days embryo Quox-1 homologous sequence was expressed in many places including neural tube, but 30 days later, tits expression sites were limited to notochord, digestive epithelium, myotome, cardiac muscle cell and periderm. The functions in control and regulation of Quox-1 gene homologous sequence during the early development of human embryo were discussed.

[Inhibitory effect of interleukin-1 beta on insulin release from isolated rat pancreatic islets and the reversal action of testosterone].

Insulin release from pancreatic islet cells of neonatal rats could be markedly inhibited by a previous incubation of cells with interleukin-1 beta (5-20 U/ml) for 20 h even under high glucose (20 mmol/L) stimulation. This inhibitory effect of IL-1 beta on insulin release could be reversed by testosterone (10(-10) mol/L), which was accompanied by an increase of the insulin content in islet cells.

Photoacousttc spectroscopy of vibrational overtones in polyatomic molecules.

Intracavity gas-phase photoacoustic spectroscopy is used to study the near IR and visible overtone spectra of propylene, 2-butene, 2-methyl-2-butene, 2,3-dimethyl-2-butene, acetone, 2-butanone, and 3-pentanone. The spectra are described in terms of the local-mode theory of vibrations as the absorption of loosely coupled anharmonic C-H oscillators within the molecule.