The ubiquitin–proteasome system regulates a variety of cellular processes including growth, differentiation and apoptosis. While E1, E2, and E3 are responsible for the conjugation of ubiquitin to substrates, deubiquitinating enzymes (DUBs) reverse the process to remove ubiquitin and edit ubiquitin chains, which have profound effects on substrates’ degradation, localization, and activities. In the present study, we found that the deubiquitinating enzyme USP47 was markedly decreased in primary colorectal cancers (CRC). Its reduced expression was associated with shorter disease-free survival of CRC patients. In cultured CRC cells, knockdown of USP47 increased pyroptosis and apoptosis induced by chemotherapeutic doxorubicin. We found that USP47 was able to bind with transcription elongation factor a3 (TCEA3) and regulated its deubiquitination and intracellular level. While ectopic expression of USP47 increased cellular TCEA3 and resistance to doxorubicin, the effect was markedly attenuated by TCEA3 knockdown. Further analysis showed that the level of pro-apoptotic Bax was regulated by TCEA3. These results indicated that the USP47-TCEA3 axis modulates cell pyroptosis and apoptosis and may serve as a target for therapeutic intervention in CRC.

Background: HSV-1 is a common pathogen that infects 50–90% of the human population worldwide. HSV-1 causes numerous infection-related diseases, some of which are severely life-threatening. There are antiviral medications with activity against HSV-1. However, with the emergence of drug-resistant mutant strains of HSV-1, there is an urgent need to develop new effective anti-HSV-1 agents. Methods: Therefore, we screened a chemical library of approximately 1500 compounds to identify inhibitors of HSV-1-induced toxicity for further drug development. Moreover, we performed several experiments, including western blot analysis, Q-PCR analysis and luciferase activity assay, to explore the antiviral mechanism of the candidates. Results: Here, we identified a small molecule, mitoxantrone dihydrochloride, with potency against HSV-1-induced toxicity. Furthermore, the viral titers and expression levels of HSV-1 viral proteins were potently reduced by the presence of MD in many cell lines. Using Q-PCR analysis, we found that MD efficiently reduced the transcription of viral genes that are essential for DNA synthesis, namely, UL5, UL9, UL29, UL30, UL42 and UL52. Notably, MD also significantly inhibited the transcription of the immediate early genes ICP0, ICP22, ICP27 and ICP47, all of which are required for the expression of early and late viral gene products. Using immunofluorescence and western blot analysis, we found that the antiviral effect of MD was independent of the activation of the NF-κB and MAPK pathways. Furthermore, we found that the reduction in the transcription of viral immediate early genes was not related to the promoter activities of ICP0. Conclusions: Therefore, the identification of compound MD as an inhibitor of toxicity induced by HSV-1 highlights its potential use in the development of novel anti-HSV-1 drugs.

Chemokine‐like factor (CKLF)‐like, MAL and related proteins for vesicle trafficking and membrane link (MARVEL) transmembrane domain‐containing family proteins (CMTMs) have significant roles in the immune system, in male reproduction, as well as in tumorigenesis. Previous studies have shown that CMTM family member 7 (CMTM7) was broadly expressed in various normal tissues, but not in lung, gastric, esophageal, pancreas, and cervix cancers. To explore its relationship with liver cancer, we examined the expression of CMTM7 in liver cancers and its correlation with clinical and pathological conditions. We found that CMTM7 expression was markedly reduced in liver cancer tissues, and negatively correlated with TNM staging and tumor metastasis. In vitro studies showed that enforced expression of CMTM7 inhibited the cell growth and migration of liver cancer cells. Further analysis revealed that CMTM7 suppressed AKT signaling and induced cell cycle arrest at the G0/G1 phase in the liver cancer cells, likely as the consequent of decreased levels of cyclin D1, cyclin‐dependent kinase 4 (CDK4), and CDK6, and increased p27 expression. Thus, CMTM7 functions as a tumor suppressor in liver cancer through suppressing cell cycle progression.

The authors sought to explore whether hypertension classification was risk factor for lobar and non‐lobar hypertensive intracerebral hemorrhage (HICH) and the prognosis in patients with hematoma. This retrospective cohort study was conducted on HICH patients admitted at the First Affiliated Hospital of Soochow University. Observations with first‐ever intracerebral hemorrhage (ICH) were recruited. The authors divided the brain image into three groups according to the location of ICH to predict whether there were significant differences between lobar and non‐lobar ICH. A Mann‐Whitney U test was used and this retrospective trial also compared the operation and mortality rates. Our cohort included 209 patients (73.7% male; median age:60.5±16.7). The overall incidence of lobar HICH was less than non‐lobar HICH (24.4% vs. 68.4%), 7.2% cases of mixed HICH was included in this analysis. In a Mann‐Whitney U test analyze, it indicated that there were significant differences in hypertension classification between lobar and non‐lobar HICH (Z = ‐3.3, p<.05). And the percentage of hematoma in lobar areas with relatively slightly high blood pressure (BP) (high normal and grade 1 hypertension) accounts for 52.9% versus 30.1% in non‐lobar areas. The increasing trends of the prevalent rate of lobar ICH with BP rising were not remarkable. The non‐lobar HICH showed a sharper increase in the condition of grade 3 hypertension compared with lobar HICH. During the period of research, the fatality of lobar hemorrhage was 2.9% versus 7.7% (non‐lobar). Besides, the fatality incidence of HICH with relatively slightly high BP (high normal and grade 1 hypertension) was lower than poorly controlled hypertensive patients (grade 2 and grade 3 hypertension). (8.0% vs. 15.7%). The increase of hypertension classification will aggravate the occurrence of non‐lobar ICH and positively corrected with BP, but not in lobar areas. It is essential to understand the distinction influence of hypertension classification between lobar and non‐lobar ICH.

The C-reactive protein/albumin ratio (CAR), Glasgow coma scale score, and blood glucose level serve as reference values to evaluate the prognosis of critically ill patients. However, the prognostic significance of the admission serum CAR for patients with moderate to severe traumatic brain injury (TBI) has remained unclear. We examined the effect of the admission CAR on the outcomes of patients with moderate to severe TBI. The clinical data from 163 patients with moderate to severe TBI were collected. Before analysis, the patients' records were anonymized and de-identified. Multivariate logistic regression analyses were used to investigate the risk factors and construct a prognostic model of in-hospital mortality. The predictive value of different models was compared by evaluating the areas under the receiver operating characteristic curve. Of the 163 patients, those who had not survived (nonsurvivors, n = 34) had had a higher CAR than that of the survivors (3.8 vs. 2.6; P < 0.001). The results of multivariate logistic regression analysis indicated that the Glasgow coma scale score (odds ratio [OR], 0.430; P = 0.001), blood glucose (OR, 1.290; P = 0.017), and CAR (OR, 1.609; P = 0.036) were independent risk factors for mortality and were used to construct the prognostic model. The area under the receiver operating characteristic curve of the prognostic model was 0.922 (95% confidence interval, 0.875-0.970), higher than that for the CAR (P = 0.0409). We had screened 195 patients for inclusion in the present study and excluded 32 patients. The CAR can serve as an independent risk factor of mortality for patients with moderate to severe TBI. Incorporating CAR into a predictive model could contribute to efficiently predicting the prognosis of adults with moderate to severe TBI.