Chromatin accessibility complex subunit 1 enhances tumor growth by regulating the oncogenic transcription of YAP in breast and cervical cancer.

Background: As a component of chromatin remodeling complex, chromatin accessibility complex subunit 1 (CHRAC1) is critical in transcription and DNA replication. However, the significance of CHRAC1 in cancer progression has not been investigated extensively. This research aimed to determine the function of CHRAC1 in breast and cervical cancer and elucidate the molecular mechanism. Methods: The Bio-ID method was used to identify the interactome of transcriptional activator Yes-associated protein (YAP) and the binding between YAP and CHRAC1 was verified by immunofluorescence. CCK8, colony formation and subcutaneous xenograft assays were conducted to explore the function of CHRAC1 in cancer cell proliferation. RNA-seq analysis and RT-PCR were used to analyze the transcription program change after CHRAC1 ablation. The diagnostic value of CHRAC1 was analyzed by TCGA database and further validated by immunohistochemistry staining. Results: In the current study, we found that the chromatin remodeler CHRAC1 was a potential YAP interactor. CHRAC1 depletion suppressed breast and cervical cancer cell proliferation and tumor growth. The potential mechanism may be that CHRAC1 interacts with YAP to facilitate oncogenic transcription of YAP target genes in Hippo pathway, thereby promoting tumorigenesis. CHRAC1 was elevated in cervical and breast cancer biopsies and the upregulation correlated with shorter survival, poor pathological stages and metastasis of cancer patients. Moreover, CHRAC1 expression was statistically associated with YAP in breast and cervical cancer biopsies. Conclusions: These findings highlight that CHRAC1 contributes to cancer progression through regulating the oncogenic transcription of YAP, which makes it a potential therapeutic target for cancer treatment.

Preparation and characterization of a self-crosslinking sodium alginate-bioactive glass sponge.

In this research, bioactive glass particles prepared by the reactive flash nanoprecipitation method (RFNP-BG particles) are used to crosslink sodium alginate to prepare biological sponges (SA-BG sponges) by freeze-drying. An experiment for the cross-linking mechanism confirms that the continuous release of Ca2+ from RFNP-BG is promoted by the crosslinking reaction and in turn leads to the gelation process of SA. Bioactive glass particles not only provide Ca2+ for the crosslinking of sodium alginate, but also enhance the mechanical properties of the SA-BG sponges. The results show that the elastic modulus of the SA-BG sponges increases from 0.026 MPa to 0.641 MPa, and the resistance to external force deformation is greatly improved; the thermal decomposition temperature increases from 105°C to 166°C; compared with a pure SA sponge, the water resistance is significantly improved. In vitro cell experiments show that the SA-BG sponges have a certain adverse effect on cell proliferation, but it is in an acceptable range. qPCR results show that the SA-BG sponges have a certain beneficial effect on promoting osteogenic gene expression. The SA-BG sponges have great application potential in the fields of medicine, hemostasis, and wound closure.

Humoral responses after inactivated COVID-19 vaccination in individuals with and without prior SARS-CoV-2 infection: A prospective cohort study.

We evaluated and compared humoral immune responses after inactivated coronavirus disease 2019 (COVID-19) vaccination among naïve individuals, asymptomatically infected individuals, and recovered patients with varying severity. In this multicenter, prospective cohort study, blood samples from 666 participants were collected before and after 2 doses of inactivated COVID-19 vaccination. Among 392 severe acute respiratory syndrome coronavirus 2-naïve individuals, the seroconversion rate increased significantly from 51.8% (median antispike protein pan-immunoglobulins [S-Igs] titer: 0.8 U/ml) after the first dose to 96% (median S-Igs titer: 79.5 U/ml) after the second dose. Thirty-two percent of naïve individuals had detectable neutralizing antibodies (NAbs) against the original strain but all of them lost neutralizing activity against the Omicron variant. In 274 individuals with natural infection, humoral immunity was significantly improved after a single vaccine dose, with median S-Igs titers of 596.7, 1176, 1086.5, and 1828 U/ml for asymptomatic infections, mild cases, moderate cases, and severe/critical cases, respectively. NAb titers also improved significantly. However, the second dose did not substantially increase antibody levels. Although a booster dose is needed for those without infection, our findings indicate that recovered patients should receive only a single dose of the vaccine, regardless of the clinical severity, until there is sufficient evidence to confirm the benefits of a second dose.

Epidemical and etiological study on hand, foot and mouth disease following EV-A71 vaccination in Xiangyang, China.

Coxsackievirus A6 (CV-A6) and Coxsackievirus A10 (CV-A10) have been emerging as the prevailing serotypes and overtaking Enterovirus A71 (EV-A71) and Coxsackievirus A16 (CV-A16) in most areas as main pathogens of hand, foot and mouth disease (HFMD) in China since 2013. To investigate whole etiological spectrum following EV-A71 vaccination of approximate 40,000 infants and young children in Xiangyang, enteroviruses were serotyped in 4415 HFMD cases from October 2016 to December 2017 using Real Time and conventional PCR and cell cultures. Of the typeable 3201 specimen, CV-A6 was the predominant serotype followed by CV-A16, CV-A10, CV-A5, CV-A2 and EV-A71 with proportions of 59.54%, 15.31%, 11.56%, 4.56%, 3.78% and 3.03%, respectively. Other 12 minor serotypes were also detected. The results demonstrated that six major serotypes of enteroviruses were co-circulating, including newly emerged CV-A2 and CV-A5. A dramatic decrease of EV-A71 cases was observed, whereas the total cases remained high. Multivalent vaccines against major serotypes are urgently needed for control of HFMD.

Effectiveness and Safety of an Inactivated Enterovirus 71 Vaccine in Children Aged 6-71 Months in a Phase IV Study.

BACKGROUND: Evaluation of a licensed inactivated enterovirus type 71 (EV71) vaccine is needed in a phase IV study with a large population to identify its effectiveness and safety for further application. METHODS: An open-label, controlled trial involving a large population of 155 995 children aged 6-71 months was performed; 40 724 were enrolled in the vaccine group and received 2 doses of inactivated EV71 vaccine at an interval of 1 month, and the remaining children were used as the control group. The EV71-infected cases with hand, foot, and mouth disease were monitored in the vaccine and control groups during a follow-up period of 14 months since the 28th day postinoculation through the local database of the Notifiable Infectious Diseases Network. The effectiveness of the vaccine was estimated by comparing the incidence density in the vaccine group versus that in the control group based upon EV71-infected patients identified via laboratory testing. In parallel, the active and passive surveillance for safety of the vaccine was conducted by home or telephone visits and by using the Adverse Event Following Immunization (AEFI) system, respectively. RESULTS: An overall level of 89.7% (95% confidence interval, 24.0-98.6%) vaccine effectiveness against EV71 infection and a 4.58% rate of reported adverse events were observed. Passive surveillance demonstrated a 0.31% rate of reported common minor reactions. CONCLUSIONS: The clinical protection and safety of the EV71 vaccine were demonstrated in the immunization of a large population. CLINICAL TRIALS REGISTRATION: NCT03001986.

Paclitaxel induced B7-H1 expression in cancer cells via the MAPK pathway.

In this study, we investigated the mechanisms by which the chemotherapeutic agent paclitaxel (PTX) induced the expression of B7-H1 immunosuppressive molecules in the human colorectal adenocarcinoma cell line SW480 and the hepatocellular carcinoma cell line HepG2. We found ptX induced B7-H1 protein expression in SW480 and HepG2 cells as demonstrated by immunofluorescence and flow cytometry and mRNA expression by using real-time quantitative polymerase chain reaction (PCR). Moreover, PTX treatment induced Erk½ phosphorylation in both cell lines. PTX-increased B7-H1 mRNA expression was significantly blocked by MEK inhibitor U0126. However, the protein expression caused by PTX was only partially blocked by U0126. Our results suggest that PTX upregulated B7-H1 expression in cultured SW480 and HepG2 cells via both transcriptional and post-transcriptional mechanisms. This may help us better understand PTX-related tumor immune evasion.