Objective To evaluate the role of protein kinase C (PKC) in reduction of hypoxia-reoxygenation (H/R) injury by hypoxic preconditioning or norepinephrine preconditioning in cultured neonatal rat cardiomyocytes. Methods Primary cultured neonatal rat cardiomyocytes were randomly divided into 6 groups (n = 25 each): control group (group Ⅰ), H/R group (group Ⅱ), hypoxia preconditioning group (group Ⅲ), norepinephrine preconditioning group (group Ⅳ), H7 + hypoxia preconditioning group (group Ⅴ) and H7 + norepinephrine preconditioning group (group Ⅵ). In group Ⅱ , the cardiomyocytes were exposed to 3 h of hypoxia followed by 1 h of reoxygenation. In group Ⅲ, the cells were subjected to 20 min of hypoxia followed by 20 min of reoxygenation before H/R. Norepinephrine was added to the culture medium with a final concentration of 10- 7 mol/L,and then the cells were cultured for 30 min before H/R in group Ⅳ. H7 was added to the culture medium with a final concentration of 5 × 10-5 mol/L, the cells were then cultured for 10 min, and the following procedures before H/R were the same as thase described in group Ⅴ . H7 was added to the culture medium with a final concentration of 5 × 10-5 mol/L, the cells were then cultured for 10 min, and the following procedures were the same as those described in group Ⅵ. The cell survival rate, the activities of LDH and CK in the supernatant, and the content of MDA and activity of SOD in cardiomyocytes were determined. Results The cell survival rate and activity of SOD were significantly lower, while the LDH and CK activities and MDA content higher in group Ⅱ than in group Ⅰ ,in group Ⅴ than in group Ⅲ, and in group Ⅵ than in group Ⅳ (P ＜ 0.01). The cell survival rate and activity of SOD were significantly increased, while the LDH and CK activities and MDA content decreased in group Ⅲ and Ⅳ compared with group Ⅱ (P＜0.01).Conclusion The activiation of PKC is involved in the reduction of H/R injury by hypoxic preconditioning or norepinephrine preconditioning in cultured neonatal rat cardiomyocytes.

Objectives To investigate the effects of nerve nutrient factors and inhibitory factors on neuronal regen? eration and axonal reconstruction at ischemic neocortical penumbra after focal cerebral ischemia in rats. Methods The rat model of middle cerebral artery ischemia was established using suture-occluded method. The pathological morpholo? gy of brain tissue was examined by using HE staining. The expression levels of GAP-43 SYN, nutrient factor (BDNF VEGF Ang1) and inhibitory factor (NogoA NogoR RhoA) were determined by using Western blotting technique. Results The number of neurons in ischemic penumbra was significantly decreased in model group (P<0.01) than in sham-operat? ed group. The expression levels of GAP-43 were significantly decreased (P<0.05) while the expression levels of NogoA NgR and RhoA in the thalamus were significantly increased (P<0.05) in model group than in sham-operated group. The expression levels of SYN and nutrient factors (BDNF VEGF Ang1) were not different between the model group and sham-operated group. Conclusion The increase in nerve inhibitory factors may contribute to the down-regulation of neu?rogenesis at ischemic neocortical penumbra after focal cerebral ischemia in rats.

Airway Remodeling ; physiology ; Animals ; Asthma ; metabolism ; Disease Models, Animal ; PPAR gamma ; biosynthesis ; Rats

Objective To analyze the characteristics of Behcet's disease (BD) with intestinal lesions to provides further reference for the diagnosis and treatment.Methods Four hundred and one cases of BD patients' data were collected including basic data,colonoscopy report,pathology diagnosis and hematologic examination.Statistical description of intestinal lesions was applied and analyzed for the differences between the locations and blood examinations of intestinal lesions.Results Within these 401 BD patients,88 (21.95 ％) with intestinal lesions.Intestinal ulcerations,including both active and inactive phase,appeared in 52 cases (12.97％) mostly founded in ileocecum,in which 62.86％ (22/ 401,5.49％ of all BD patients) without the abdominal discomfort.Compared with inactive phase,the active phase intestinal BD patients have higher inflammation indexes with C reactive protein (CRP) increased of statistical significance (P =0.028).Thirty-three cases (8.23 ％) with adenomas were founded,including tubular adenoma,serrated adenoma and villous adenoma.Mostly occurred in rectum,sigmoid colon,especially the sigmoid colon rectum junction.Adenomas were seen in eider patients with statistical significance compared to BD patients without intestinal lesion or with intestinal ulceration (P =0.022,0.000),and exhibited elder changes of lab tests,such as increas in aspartate aminotransferase (AST),gamma-glutamyl transferase (GGT) and uric acid (UA).In addition,2 cases of melanosis coli and 1 case of caecal diverticulum were also founded.Conclusions BD patients with intestinal ulcer or adenoma takes a fairly high ratio,and most intestinal BD and BD with adenoma patients did not complaint related symptoms,so colonoscopy as a screening method for diagnosis and treatment of BD is necessary.

The new generation of artificial intelligence technology,represented by deep learning,has emerged as a crucial driving force in the advancement of new drug research and development.This article creatively proposes a workflow named"Molecular Factory"for the design and optimization of drug molecules based on artificial intelligence technology.This workflow integrates intelligent molecular generation models,high-performance molecular docking algorithms,and accurate protein-ligand binding affinity prediction methods.It has been integrated as a core module into DrugFlow,a one-stop drug design software platform,providing a comprehensive set of mature solutions for the discovery and optimization of lead compounds.Utilizing the"Molecular Factory"module,we conducted the research of second-generation inhibitors against Menin that can combat drug resistance.Through the integration of computational and experimental approaches,we rapidly identified multiple promising compounds.Among them,compound RG-10 exhibited the IC50 values of 9.681 nmol/L,233.2 nmol/L,and 40.09 nmol/L against the wild-type Menin,M327I mutant,and T349M mutant,respectively.Compared to the positive reference molecule SNDX-5613,which has entered Phase Ⅱ clinical trials,RG-10 demonstrated significantly enhanced inhibitory activity against the M327I and T349M mutants.These findings fully demonstrate the unique advantages of the"Molecular Factory"technology in practical drug design and development scenarios.It can rapidly and efficiently generate high-quality active molecules targeting specific protein structures,holding significant value and profound implications for advancing new drug discovery.