Amyotrophic lateral sclerosis (ALS) is the most prevalent motor neuron disease in adults. Currently, there are no known drugs or clinical approaches that have demonstrated efficacy in treating ALS. Mitochondrial function and autophagy have been identified as crucial mechanisms in the development of ALS. While Bax inhibitor 1 (BI1) has been implicated in neurodegenerative diseases, its exact mechanism remains unknown. This study investigates the therapeutic impact of BI1 overexpression on ALS both in vivo and in vitro, revealing its ability to mitigate SOD1G93A-induced apoptosis, nuclear damage, mitochondrial dysfunction, and axonal degeneration of motor neurons. At the same time, BI1 prolongs onset time and lifespan of ALS mice, improves motor function, and alleviates neuronal damage, muscle damage, neuromuscular junction damage among other aspects. The findings indicate that BI1 can inhibit pathological TDP43 morphology and initially stimulate autophagy through interaction with TDP43. This study establishes a solid theoretical foundation for understanding the regulation of autophagy by BI1 and TDP43 while shedding light on the pathogenesis of ALS through their interaction - offering new concepts and targets for clinical implementation and drug development.

A novel pyrene excimer-based hairpin probe with a nick at the stem was developed to directly evaluate the single-strand break repair(SSBR) ability. In the existence of appropriate activity of DNA repair-associated enzymes (DREs), the oligonucleotide probe could prevent the digestion of Bst DNA polymerase and keep the long-wavelength excimer signal. However, in the absence of DREs, the nicked probe could be digested by Bst DNA polymerase, bringing about a "turn-off" monomer fluorescence signal. Therefore, the fluorescence changes of the probe could be used to directly evaluate the SSBR capability. After feasibility verification and a series of conditions optimization, the assessment of SSBR capacity by nucleoprotein extracted from different cells was investigated and the results showed that, compared to the primary cell, the tumor cell lines do not have the ability of SSBR. We also explored the defi ciency of tumor cells SSBR by compensation with extra SSBR key enzymes and the results indicated that something might inhibit the SSBR in tumor cell lines. Furthermore, the reporter system could detect SSBR of 500 cells and was successfully applied to anti-aging drug screening. The advantages of this method include simple procedure, less time, and good repeatability, and this method can be used for the rapid detection of SSBR capacity of different cells.

Aquaporin 1 (AQP1) is expressed in most microvasculature endothelial cells and forms water channels that play major roles in a variety of physiologic processes. This study aimed to delineate the transcriptional regulation of AQP1 by Mef2c in endothelial cells. Mef2c cooperated with Sp1 to activate human AQP1 transcription by binding to its proximal promoter in human umbilical cord vein endothelial cells (HUVEC). Over-expression of Mef2c, Sp1, or Mef2c/Sp1 increased HUVEC migration and tube-forming ability, which can be abolished AQP1 knockdown. These data indicate that AQP1 is a direct target of Mef2c in regulating angiogenesis and vasculogenesis of endothelial cells.

Objective To study the mechanism of wortmannin (WM) in enhancing radiosensitivity of malignant glioma cells.Methods Human glioma cells (U251) were pretreated with 10 μmol/L WM for 2 h and then irradiated with 10 Gy X-rays.The changes of cell cycle and apoptosis ratio were examined.Western Blot and immunofluorescence staining were used to detect the expression and function of ATM and its target genes as well as DNA-PKcs.Results The ratio of apoptotic cells in the WM combined with X-ray treatment group (WM + IR) was increased from (5.3 ± 0.66) ％ of control group and (11.5 ± 2.0) ％ of IR group to (21.8 ± 2.4) ％ significantly (F =57.38,P ＜ 0.05).Along with the increase of apoptosis,the expression of cleave-caspase-3 was significantly increased in IR or WM + IR group compared to control group (q =12.49,19.19,P ＜ 0.05),and its enhancement in WM + IR group was more significant than that in IR group (q =6.70,P ＜ 0.05).Compared to control group,the cell cycle assay showed that the amount of U251 cells in G2/M phase was increased in IR group (q =9.67,P ＜ 0.05),and further increased in WM + IR group (q =21.25,P ＜ 0.05),indicating an obvious G2/M phase arrest.Moreover,WM could effectively inhibit the phosphorylation of ATM kinase and the activity of ATM downstream target genes of p53 and SMC1.WM also suppressed the IR-induced expressions of DNAPKcs and phospho-γH2AX (Ser139).Conclusions WM effectively increased the radiation sensitivity of malignant glioma cells through down-regulating the activity of ATM kinase and DNA-PK.

Objective To investigate the expression of transcription factor GATA-2 genes in the bone marrow MSCs from children with aplastic anemia(AA)and normal controls.Methods We collected bone marrow samples from thirty-eight aplastic anemia patients and normal persons,The expression of GATA-2 genes were analyzed by using QRTPCR in the MSCs from 20 normal controls and 38cases with AA.The expression levels of GATA-2 genes in the MSCs from children with AA were compared before and after therapy.Results GATA-2expression by MSCs from AA patients at diagnosis was significantly lower than in normal controls(p0.05).After two years of immunosuppressive therapy(IST),expression of GATA-2from responders was significantly higher than those at diagnosis.It was no difference in the expression level of GATA-2gene within the MSCs from normal controls and responders.Conclusion The lower expression of GATA-2in the MSCs from children with AA may influence the regulation of hematopoiesis and play the role in pathogenesis of AA.

Objective Through detecting the expression of dentin matrix protein 1(C-DMP1) in pleomorphic adenoma and mucoepidermoid carcinoma tissues to investigate the role of expression of C-DMP1 in the oncogenesis of salivary gland tumor.Methods The immunohistochemical method was used to observe the expression of C-DMP1 in 30 cases of benign salivary gland tumor and 30 cases of malignant salivary gland tumors.Results In mucoepidermoid carcinomas,the expression of C-DMP1 in the epidermoid cells was strongly positive,in the nuclei part of the intermediate cells was weakly positive,while the mucous cells were negative,the strongly positive expression rate was 73.3%;In pleomorphic adenoma,part of the nuclei of ductal cells,outer myoepithelial cells and cartilage-like cells were weakly positive,with only a few strongly positive,the strongly positive expression rate was 6.6%.There was significant difference in the stongly positive expression rate of C-DMP1 between benign and malignant tumors in salivary gland(P0.05).Conclusion The expression of C-DMP1 in the benign and malignant salivary gland tumor tissue has different changes in its distribution,it suggests that C-DMP1 may participate in the oncogenesis of salivary gland tumor.

Objective To explore the effects of XIAP on carcinogenesis and progression of breast cancer.(Methods The) expressions of XIAP in the tissues of normal mammary(96 cases),cystic hyperplasia mammary((56 cases),) atypical hyperplasia mammary(12 cases),and breast cancer(119 cases) were evaluated by SP immunohistochemistry.The relationships between XIAP expression and the pathologically biological features of breast cancer were assessed.Results The positive rates of XIAP in the tissues of normal mammary,cystic hyperplasia mammary,atypical hyperplasia mammary and breast cancer were 4.2%(4/96),5.4%(3/56),42.7%(5/12) and 72.3%(86/119),respectively.The positive rates in the last two groups were higher than those in the former two groups(P0.05).XIAP was more expressed in the infiltrative non-special breast cancer(82.0%,73/89) than in the special and early stage infiltrative breast cancer(37.5%,3/8)(P0.05). Expression of XIAP was increased in breast cancer with lymph node metastasis although the difference was not significant(P0.05).Conclusion Overexpression of XIAP is common in carcinogenesis and progression of breast cancer.Altered expression of XIAP may contribute to carcinogenesis and progression of breast cancer by inhibiting apoptosis,its overexpression indicates worse prognosis.