Integrated serum proteomic and N-glycoproteomic characterization of dengue patients.

Dengue fever is a mosquito-borne viral disease caused by the dengue virus (DENV). It poses a public health threat globally and, while most people with dengue have mild symptoms or are asymptomatic, approximately 5% of affected individuals develop severe disease and need hospital care. However, knowledge of the molecular mechanisms underlying dengue infection and the interaction between the virus and its host remains limited. In the present study, we performed a quantitative proteomic and N-glycoproteomic analysis of serum from 19 patients with dengue and 11 healthy people. The results revealed distinct proteomic and N-glycoproteomic landscapes between the two groups. Notably, we report for the first time the changes in the serum N glycosylation pattern following dengue infection and provide abundant information on glycoproteins, glycosylation sites, and intact N-glycopeptides using recently developed site-specific glycoproteomic approaches. Furthermore, a series of key functional pathways in proteomic and N-glycoproteomic were identified. Collectively, our findings significantly improve understanding of host and DENV interactions and the general pathogenesis and pathology of DENV, laying a foundation for functional studies of glycosylation and glycan structures in dengue infection.

Combination of saikosaponin c and telbivudine synergistically enhances the anti-HBV activity.

OBJECTIVE: The present study was undertaken to obtain data using the combination of SSc and lamivudine (LAM), entecavir (ETV) or telbivudine (LdT) in HepG2.2.15 cells to explore whether SSc acts as a potent adjuvant of nucleoside analogues in anti-HBV treatment. METHODS: HepG2.2.15 cells were incubated with either SSc combined with any one of three nucleoside analogues (NAs) LAM, ETV, LdT or only one of them for 48 h. The expression profiles of HBV DNA, HBsAg, HBeAg, and HBcAg were examined by real-time quantitative PCR, ELISA, and western blot. RESULTS: Compared with mono-drug treatment, the combination of SSc and any of the three nucleoside analogues significantly promoted additional reduction on HBV DNA level. Declined levels of HBsAg, HBeAg, and HBcAg were observed in SSc and LdT combination group. CONCLUSION: These in vitro results indicated that SSc acted as a promising nucleoside analogue adjuvant, especially for telbivudine in the therapeutic strategies against HBV infection.

Saikosaponin C exerts anti-HBV effects by attenuating HNF1α and HNF4α expression to suppress HBV pgRNA synthesis.

OBJECTIVE: Saikosaponin c (SSc), a compound purified from the traditional Chinese herb of Radix Bupleuri was previously identified to exhibit anti-HBV replication activity. However, the mechanism through which SSc acts against HBV remains unknown. In this study, we investigated the mechanism of SSc mediated anti-HBV activity. METHODS: HepG2.2.15 cells were cultured at 37 â„ƒ in the presence of 1-40 µg/mL of SSc or DMSO as a control. The expression profile of HBV markers, cytokines, HNF1α and HNF4α were investigated by real-time quantitative PCR, Elisa, Western blot and Dot blotting. Knockdown of HNF1α or HNF4α in HepG2.2.15 cells was mediated by two small siRNAs specifically targeting HNF1α or HNF4α. RESULTS: We found that SSc stimulates IL-6 expression, leading to attenuated HNF1α and HNF4α expression, which further mediates suppression of HBV pgRNA synthesis. Knockdown of HNF1α or HNF4α in HepG2.2.15 cells by RNA interference abrogates SSc's anti-HBV role. Moreover, SSc is effective to both wild-type and drug-resistant HBV mutants. CONCLUSION: SSc inhibits pgRNA synthesis by targeting HNF1α and HNF4α. These results indicate that SSc acts as a promising compound for modulating pgRNA transcription in the therapeutic strategies against HBV infection.

Geographic Differences on Clinical Manifestations of COVID-19 Infection Between Overseas Chinese and Local Chinese Patients.

INTRODUCTION: The novel coronavirus (COVID-19) has become a global pandemic with sharp rises in the number of confirmed cases and rapid spread across the world. Here, we looked at the effects of geographic differences on clinical manifestations of SARS-CoV-2 infected patients. METHODS: A total of 114 confirmed COVID-19 patients were included in this study. The epidemiological, demographic, clinical, as well as laboratory findings were extracted from the electronic medical records of these patients. RESULTS: We report the observation that patients from overseas residents diagnosed with COVID-19 were mildly symptomatic with cough and presented with lower inflammatory response and attenuated virus clearance rate, as well as correspondingly prolonged days of hospital stay than local Chinese patients. Moreover, the receiver-operating characteristic (ROC) analysis, performed to provide a measure of the difference between two groups, showed that serum albumin had the highest area under the curve value (0.81, p < 0.001). DISCUSSION: Our results suggested that blood albumin level acted as a predictive value in distinguishing clinical features between local and overseas Chinese. This work underscores the need to identify distinguishably prognostic factors of geographical dissimilarity in COVID-19 patients.

TBK1 Promote Bladder Cancer Cell Proliferation and Migration via Akt Signaling.

Bladder cancer is a challenging and fatal malignancy and the improvement in prognosis is limited over years. Deep understanding the mechanism of bladder cancer tumorigenesis and progression will help to discover novel and effective treatment strategies. In this study, we identify non-canonical IkB kinase TBK1 is up-regulated in bladder cancer tissue and cell lines. Knockdown of TBK1 markedly inhibits cell proliferation and migration. Inhibition of TBK1 kinase activity by BX795 significantly attenuates bladder cancer cell proliferation and migration. Mechanistic study shows that overexpression of TBK1 promoted the phosphorylation of Akt, whereas knockdown of TBK1 reverses this action. Taken together, our data suggest that TBK1 modulates the malignant behaviors of bladder cancer cell via Akt signaling, revealing new insights in discovering new therapy target for bladder cancer.