BACKGROUND:Pathogenesis of Parkinson’s disease is not completely understood, and there is yet no effective therapy that can prevent the neurodegenerative process of the disease fundamentaly. OBJECTIVE:To explore the effects of pituitary adenylate cyclase-activating polypeptide (PACAP) on lactacystin-induced Parkinson’s disease dopaminergic PC12 cel apoptosis and its molecular mechanism. METHODS: Under induction by nerve growth factors, PC12 cels differentiated into dopaminergic neurons, and then were treated with different concentrations of lactacystin for different time. When the cel survival rate was about 50%,the concentration and action time oflactacystin were selected to establish cel models of Parkinson’s disease. In the study, there were control group, lactacystin group, PACAP1-27 group (intervention group 1) and PACAP1-27+PACAP6-27 co-intervention group (intervention group 2). Changes of cel morphology were observed under inverted microscope; cel viability was detected with MTT method; the expression of endoplasmic reticulum stress specific protein caspase-12 was detected by western blot. Then the action of PACAP1-27 and PACAP6-27 to the cytoxicity of lactacystin was observed. RESULTS AND CONCLUSION: With different concentrations and action time of lactacystin, the viability of PC12 cels presented a concentration- and time-dependent decline. When the lactacystin at 20μmol/L acted for 24 hours, the cel viability was declined by about 50%. Under same conditions of lactacystin concentration and action time (20 μmol/L, 24 hours), the cels in the lactacystin group appeared to have damaged changes, declined cel viability, and increased caspase-12 activity in comparison with the control group (P< 0.01). Compared with the lactacystin group, the cel damage was relieved and cel viability was increased significantly in the intervention group 1 as wel as the expression of caspase-12 was decreased (P < 0.01). Experimental findings in the intervention group 2 were similar to those in the lactacystin group. These results suggest that lactacystin, an ubiquitin proteasome inhibitor, can lead to cel damage; PACAP1-27 plays a protective role by regulating the above-mentioned signal pathway. As one PACAP1-27 receptor antagonist, PACAP6-27 can attenuate this effect of PACAP1-27.

Objective:To explore the level changes of common laboratory indexes in patients with ischemic stroke (IS) with different infarct sizes and their clinical application value.Methods:The baseline data of 237 patients hospitalized in Lanzhou University Second Hospital from June 2019 to December 2020 and their laboratory indicators within 24 hours of admission were collected. The patients were divided into lacunar group ( n=80) and infarct group ( n=157) according to the infarct area. The experimental indexes and clinical data of the two groups were compared. Binary logistic regression was used to screen the independent influencing factors of infarct size and establish a joint diagnostic model. The receiver operating characteristic (ROC) curve and model calibration chart were used to verify the clinical application value of each index. Results:The levels of cholesterol (CHO)/high density lipoprotein (HDL), low density lipoprotein (LDL)/HDL, neutrophil count, Cystatin C (Cys C), phosphorus (PHOS), indirect bilirubin (IBIL), LDL, apolipoprotein (ApoB), homocysteine (HCY), D-dimer, smoking, drinking, overweight and arterial stenosis in the infarct group were higher than those in the lacunar group (all P<0.05), and the levels of apolipoprotein A Ⅰ (ApoAⅠ)/ApoB, ApoAⅠ and carbon dioxide (CO 2) in the infarct group were lower than those in the lacunar group (all P<0.05). ApoA Ⅰ/ApoB and CO 2 were independent protective factors of infarct size (all P<0.05); Cys C, PHOS and IBIL were independent risk factors of infarct size (all P<0.05). The combined prediction model of CO 2, PHOS, IBIL, ApoA Ⅰ/ApoB and Cys C has good prediction efficiency for infarct area, and the area under the curve (AUC) of combined diagnosis was 0.739. Conclusions:Laboratory indicators are closely related to the infarct size of IS. The model developed in this study have good clinical value, which provides a new basis for IS evaluation and early warning.

OBJECTIVETo evaluate Amifostin's effect on protecting kidney from cisplatinum (DDP) injury and its adverse reactions and safety.

METHODS193 Patients were divided into two groups randomly: 102 in group A (treatment group) and 91 in group B (control group). Indexes such as blood routine, blood calcium, liver function, blood urea nitrogen (BUN), cretinine (C), and urinary N-acetyl-beta-D-glucosaminidase (NAG)/C and micro-albumin (MAB/C) were monitored at different intervals before or after treatment.

RESULTSIn the two courses of treatment in both groups, the deviation (D) values of MAB/C before treatment and on D2 in group A were lower than those in grop B (P < 0.05), so were those before treatment and on D4, D6, D10 and D14 (P < 0.01). The D-values of NAG/C before treatment and on D4, D6, D10 and D14 in the first course of group A were obviously lower than those on the corresponding days in group B (P < 0.01), so were those before treatment and on D2, D4, D6, D10 and D14 in the second course (P < 0.01).

CONCLUSIONThe reduction of MAB/C and NAG/C by Amifostin in group A demonstrates that: Amifostin is able to effectively protect the renal function, regardless of the type of tumor. In contrast with group B, Amifostin in group A shows no protection for tumor in lung cancer and ovarian cancer. The main side effects of Amifostin are mild hypotension, nausea, vomiting and hypocalcemia in some patients.

Adult ; Aged ; Amifostine ; adverse effects ; therapeutic use ; Antineoplastic Agents ; adverse effects ; Cisplatin ; adverse effects ; Humans ; Kidney Diseases ; chemically induced ; prevention & control ; Middle Aged ; Protective Agents ; adverse effects ; therapeutic use

OBJECTIVE: To explore the pathogenesis of gastric cancer through a bioinformatic approach to provide evidence for the prevention and treatment of gastric cancer. METHODS: The differentially expressed genes (DEGs) in gastric cancer and normal gastric mucosa in GSE79973 dataset were analyzed using GEO2R online tool. GO analysis and KEGG pathway enrichment analysis of the DEGs in DAVID database were performed. The protein interaction network was constructed using STRING database, and the key genes (Hub genes) were screened and their functional modules were analyzed using Cytoscape software. The GEPIA database was used to validate the Hub genes, and the Target Scan database was used to predict the microRNAs that regulate the target genes; OncomiR was used to analyze the expressions of the microRNAs in gastric cancer tissues and their relationship with the survival outcomes of the patients. RESULTS: A total of 181 DEGs were identified in gastric cancer, and 10 hub genes were screened by the protein- protein interaction network. Functional analysis showed that these DEGs were involved mainly in protein digestion and absorption, PI3K-Akt signaling pathway, ECM-receptor interaction and platelet activation signal pathway. GEPIA database validation showed that COL1A1 was highly expressed in gastric cancer tissues and was associated with a poor prognosis of patients with gastric cancer. MiR-129-5p was found to bind to the 3'UTR of COL1A1 mRNA, and compared with that in normal tissues, miR-129-5p expression was obviously down-regulated in gastric cancer tissues, and was correlated with the prognosis of the patients. CONCLUSIONS COL1A1 under regulation by MiR-129-5p is a potential therapeutic target for gastric cancer.
Collagen Type I ; drug effects ; Computational Biology ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; MicroRNAs ; therapeutic use ; Phosphatidylinositol 3-Kinases ; Stomach Neoplasms ; drug therapy