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The outbreak of coronavirus disease (COVID-19) caused by SARS-CoV-2 virus continually lead to worldwide human infections and deaths. Currently, there is no specific viral protein-targeted therapeutics. Viral nucleocapsid protein is a potential antiviral drug target, serving multiple critical functions during the viral life cycle. However, the structural information of SARS-CoV-2 nucleocapsid protein remains unclear. Herein, we have determined the 2.7 Å crystal structure of the N-terminal RNA binding domain of SARS-CoV-2 nucleocapsid protein. Although the overall structure is similar as other reported coronavirus nucleocapsid protein N-terminal domain, the surface electrostatic potential characteristics between them are distinct. Further comparison with mild virus type HCoV-OC43 equivalent domain demonstrates a unique potential RNA binding pocket alongside the -sheet core. Complemented by binding studies, our data provide several atomic resolution features of SARS-CoV-2 nucleocapsid protein N-terminal domain, guiding the design of novel antiviral agents specific targeting to SARS-CoV-2.
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OBJECTIVES@#To investigate the roles of cytoskeleton-associated protein 2 (CKAP2) in proliferation, apoptosis, and migration in liver cancer cells and the potential mechanisms.@*METHODS@#Human normal hepatocyte L02 and liver cancer cell lines HepG2, Huh7, and SMMC-7721 were cultured. The CKAP2 expression was detected by real-time PCR and Western blotting. HepG2 cells were randomly divided into a control group, a negative control (NC) group, and a CKAP2 silencing (siCKAP2) group. CCK-8 and BrdU assays were used to evaluate cell viability and proliferation, respectively. Transwell assay was employed to determine cell migration and invasion. The protein levels of cleaved-caspase 3, Bax, E-cadherin, N-cadherin, Vimentin, phosphorylated Janus kinase 2 (p-JAK2), and phosphorylated signal transducer and activator of transcription 3 (p-STAT3) were determined by Western blotting.@*RESULTS@#Compared with normal hepatocyte L02, CKAP2 was highly expressed in liver cancer cell lines HepG2, Huh7, and SMMC-7721 (all <0.05). Compared with the NC group, cell viability and proliferation rate of the siCKAP2 group were decreased (both <0.05). The apoptotic rate, protein expression of cleaved-caspase 3 and Bax in the siCKAP2 group were significantly higher than those in the NC group (all <0.05). Compared with the NC group, cell migration and invasion rates of the siCKAP2 group were significantly attenuated (both <0.05). Compared with the NC group, E-cadherin protein expression in siCKAP2 group was increased, while protein expression levels of Vimentin, N-cadherin, p-JAK2, and p-STAT3 were decreased (all <0.05).@*CONCLUSIONS@#CKAP2 gene silence inhibits proliferation, migration, and invasion, and promotes apoptosis in liver cancer cells, while JAK2/STAT3 signaling pathway may be involved in these processes.
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Humans , Apoptosis , Cell Line, Tumor , Cell Movement , Cell Proliferation , Cytoskeleton , Liver Neoplasms , GeneticsABSTRACT
Objective To observe the effect of vibration therapy of Mongolian medicine on headache and vertigo in concussion patients.Method A hundred eligible subjects with concussion were randomized into a treatment group of 50 cases and a control group of 50 cases. The treatment group was intervened by brain vibration therapy of Mongolian medicine, while the control group was treated with Piracetam tablets. The scores of headache and vertigo in the two groups were observed before the treatment and respectively after 3-day, 6-day, and 9-day treatment. Result After 3-day, 6-day, and 9-day treatment, respectively, the scores of headache and vertigo were significantly different from those before the treatment in both groups (P<0.05). The scores of headache and vertigo respectively after 3-day, 6-day and 9-day treatment in the treatment group were significantly different from those in the control group (P<0.05). Conclusion The brain vibration therapy of Mongolian medicine is effective in treating headache and vertigo in concussion.
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Background and purpose:Microsatellite instability (MSI) status is commonly applied to predict the prognosis and chemosensitivity in stage Ⅱ and stage Ⅲ colorectal cancer patients. However, researches of its function on metastasis colorectal cancer are limited. This study investigated its value on prognosis and chemosensitivity in metastatic colorectal cancer (CRC) patients.Methods:We retrospectively investigated tumor tissues from metastasis CRC patients who were treated with oxaliplatin and 5-FU-based therapy regimens (FOLFOX and XELOX). Immunostaining of proteins of the mismatch repair genehMLH1,hMSH2,hMSH6 andhPMS2 was performed. Prognostic value and chemosensitivity in patients with MSI status were also determined.Results:Clinical features from 113 patients were analyzed. No cor-relation of overall survival (OS) and chemosensitivity with MSI status was found. We further investigated 79 patients with synchronous metastasis and palliatively tumor resection. Median progression free survival (PFS) from 22 MSI patients was significant longer than that in 57 MSS patients (19.9 monthsvs 7 months,P=0.005). No significant difference was seen in OS comparison (P=0.07). MSI status was also an independent prognostic factors of PFS by Cox multivariate analysis (MSS/MSI,HR=2.079,P=0.043). Moreover, in this group, MSI patients had improved disease control rate (59.1%vs 31.6%, P=0.025) in chemosensitivity analysis than MSS patients.Conclusion:A better PFS in MSI patients with synchronous metastasis and palliative tumor resection was found after treated with oxaliplatin and 5-FU-based therapy and a better chemosensitivity in MSI patients was also found.
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Marine Actinobacteria are emerging as new resources for bioactive natural products with promise in novel drug discovery. In recent years, the richness and diversity of marine Actinobacteria from the South China Sea and their ability in producing bioactive products have been investigated. The objective of this work is to isolate and identify bioactive secondary metabolites from a marine actinobacterium SCSIO 1934 derived from sediments of South China Sea. The strain was identified as a Streptomyces spieces by analyzing its 16S rDNA sequence. Streptomyces sp. SCSIO 1934 was fermented under optimized conditions and seven bioactive secondary metabolites were isolated and purified by chromatographic methods including colum chromatography over silica gel and Sephadex LH-20. Their structures were elucidated as 17-O-demethylgeldanamycin (1), lebstatin (2), 17-O-demethyllebstatin (3), nigericin (4), nigericin sodium salt (5), abierixin (6), respectively, by detailed NMR spectroscopic data (1H, 13C, COSY, HSQC and HMBC). This work provided a new marine actinobacterium Streptomyces sp. SCSIO 1934, capable of producing diverse bioactive natural products.
Subject(s)
Anti-Bacterial Agents , Chemistry , China , DNA, Ribosomal , Chemistry , Genetics , Geologic Sediments , Microbiology , Oceans and Seas , RNA, Ribosomal, 16S , Genetics , Streptomyces , Chemistry , Classification , GeneticsABSTRACT
Objective To evaluate the effect of double tractors swing microendoscopic discectomy technique in multi-segmental lumbar disc herniation. Methods From December 2006 to November 2009,153 patients with multi-segmental lumbar disc herniation were treated with double tractors swing microendoscopic discectomy. They included 85 cases of multi-segmental disc herniation, 53 cases of degenerative canal stenosis and 15 cases of lumbar instability. Among them, 2, 3, 4 and 5 fenestrations were performed in 105,33, 13 and 2 cases respectively and interbody fusion was done with "quanhe" inflation cage and screws in 15 cases. The results were evaluated with Macnab scale. Results All the 153 patients were followed from 3to 36 months, with an average of 16 months. The mean operative time was 45, 61, 83 and 110 min for 2,3,4 and 5 fenestrations respectively, with a mean blood loss of 150 ml. And it took extra 92 min to finish interbody fusion. Complications included dural sac tears in 1 case,canda equina slight lesion in 1, superficial incision infection in 1, the formation of deep venous thrombosis in 1, and revision for"quanhe"inflation cage in 1. The mean hospital stay was 10 days. Excellent results were obtained in 117 cases, good in 32 and fair in 4. One hundred and thirty-two patients returned to their work or normal activities in 3 weeks. One hundred and forty-nine cases were satisfied with the therapeutic effect. Conclusion This technique not only can reach adjacent intervertebral space easily but also disperse pressure on the nerve root effectively. This technique can provide thorough decompression and good results.
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Functional proteins designed de novo have potential application in chemical engineering, agriculture and healthcare. Metal binding sites are commonly used to incorporate functions. Based on a de novo designed protein DS119 with a βαβ structure, we have computationally engineered zinc binding sites into it using a home-made searching program. Seven out of the eight designed sequences tested were shown to bind Zn(2+) with micromolar affinity, and one of them bound Zn(2+) with 1:1 stoichiometry. This is the first time that metalloproteins with an α, β mixed structure have been designed from scratch.