A novel one-pot three-component cascade cyclization strategy for the synthesis of 2-amino-5-acylthiazoles using enaminones, cyanamide, and elemental sulfur has been developed. The reported methods have demonstrated good tolerance of various functional groups. Up to 28 2-amino-5-acylthiazole compounds bearing diverse structural differences were successfully synthesized from easily obtained starting materials with moderate to excellent yields. Our method provides an effective way for the access of valuable and potentially bioactive 2-amino-5-acylthiazole derivatives.

Decompression sickness (DCS) occurs when ambient pressure is severely reduced during diving and aviation. Hyperbaric oxygen (HBO) pretreatment has been shown to exert beneficial effects on DCS in rats via heat-shock proteins (HSPs). We hypothesized that HBO pretreatment will also reduce DCS via HSPs in swine models. In the first part of our investigation, six swine were subjected to a session of HBO treatment. HSP32, 60, 70 and 90 were detected, before and at 6, 12, 18, 24 and 30 h following exposure in lymphocytes. In the second part of our investigation, another 10 swine were randomly assigned into two groups (five per group). All swine were subjected to two simulated air dives in a hyperbaric chamber with an interval of 7 days. Eighteen hours before each dive, the swine were pretreated with HBO or air: the first group received air pretreatment prior to the first dive and HBO pretreatment prior to the second; the second group were pretreated with HBO first and then air. Bubble loads, skin lesions, inflammation and endothelial markers were detected after each dive. In lymphocytes, all HSPs increased significantly (<0.05), with the greatest expression appearing at 18 h for HSP32 and 70. HBO pretreatment significantly reduced all the determined changes compared with air pretreatment. The results demonstrate that a single exposure to HBO 18 h prior to diving effectively protects against DCS in the swine model, possibly via induction of HSPs.

After the attack of cerebral aneurysm, proteins like Cathepsin B, Caspase-3 and p-JNK are all involved in the apoptosis of VSMCs. This process may be realized by Cathepsin B which activates the apoptosis mechanism of Caspase-3 and mediate the apoptosis of VSMC through the JNK signaling pathway. Therefore, silencing Cathepsin B gene or inhibiting the conduction through JNK signaling pathway can mitigate the apoptosis of vascular smooth muscle cells in cerebral aneurysm.

Background Most immune thrombocytopenia (ITP) is sporadic but a positive family history of ITP in some patients suggests that hereditary forms exist. Because of the rarity of familial ITP families available for study and the heterogeneity of sporadic ITP, family linkage analysis or genome-wide association studies are limited. Objectives Based on one ITP pedigree, we try to identify the predisposing gene in familial or sporadic ITP and reveal the way in which it causes thrombocytopenia. Methods Gene expression profiling analysis and whole-exome sequencing were performed on samples from family members with ITP, sporadic ITP cases and healthy individuals. We also evaluated the influence of potential pathogenic mutation on immune function and megakaryocyte apoptosis. Results Whole-exome sequencing identified a potential pathologic p.G76S heterozygous mutation on the TNFRSF13B gene in familial ITP patients. ITP patients harboring the G76S mutation displayed an upregulated 'cytokine-cytokine receptor interaction' signal, increased serum TNFα, IL-17α, IFNγ and BAFF levels, and enhanced binding capacity of APRIL ligand to B cells. Additionally, Epstein-Barr virus (EBV)-transformed B cells with the G76S mutation could induce human megakaryocyte line (Meg-01) apoptosis significantly. Conclusion p.G76S mutation on the TNFRSF13B gene is responsible for ITP, and is a genetic predisposing factor for familial or sporadic ITP.

MicroRNA‑23b‑3p (miR‑23b‑3p) has been reported to be involved in the pathogenesis of a number of diseases, including non‑small cell lung cancer and gastric cancer, by acting on different signaling pathways. The present study aimed to understand the association between the miR‑23b‑3p level of intracranial aneurysms (IAs) and the mechanism involved. Computational analysis was used to search for the target of miR‑23b‑3p, and luciferase assay was used to validate the miRNA/target association. Western blot analysis and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to determine the expression of miR‑23b‑3p and phosphatase and tensin homolog (PTEN), and their expression in smooth muscle cells (SMCs) treated with miRNA mimic or inhibitor. Firstly, an online miRNA database (www.mirdb.org) was searched using the 'seed sequence' located within the 3'‑untranslated region of the target gene, and then PTEN was validated as the direct target gene via a luciferase reporter assay system. The negative regulatory association between miR‑23b‑3p and PTEN was determined through the analysis of the relative luciferase activity. Additionally, RT-qPCR and western blot analysis was performed in order to assess the mRNA and protein expression levels of PTEN among IA (n=32) and control (n=17) groups or cells treated with scramble control, miR‑23b‑3p mimics, PTEN siRNA and miR‑23b‑3p inhibitors to verify the negative regulatory association between miR‑23b‑3p and PTEN. Experiments were then performed to investigate the effect of miR‑23b‑3p and PTEN on the viability and apoptosis of pulmonary artery SMCs (PASMCs). The results showed that cells transfected with miR‑23b‑3p inhibitors suppressed the viability of SMCs by promoting the apoptosis of the cells compared with that of the scramble controls, while cells transfected with miR‑23b‑3p mimics and PTEN siRNA enhanced the viability of VSMCs by inducing apoptosis. This indicated that miR‑23b‑3p negatively interfered with the viability of the cells, while PTEN positively interfered with the viability of the cells. In conclusion, PTEN was found to be a virtual target of miR‑23b‑3p, and a negative regulatory association existed between miR‑23b‑3p and PTEN. miR‑23b‑3p and PTEN interfered with the viability and apoptosis of SMCs.