Bacteremia Caused by a Serotype Ob5 Vibrio cholerae Strain in a Cirrhotic Patient in China.

The increasing incidence of non-O1/non-O139 Vibrio cholerae (NOVC) has been observed worldwide. However, septicemia caused by NOVC remains a rare condition that has received limited attention. Currently, there are no established treatment guidelines for bloodstream infections caused by NOVC, and the understanding of this condition mainly relies on individual case reports. Although NOVC bacteremia can be fatal in a small percentage of cases, knowledge about its microbiological features remains limited. Here, we present a case of V. cholerae septicemia caused by NOVC in a 46-year-old man with chronic viral hepatitis and liver cirrhosis. The isolated strain, named V. cholerae VCH20210731 and classified as a new sequence type (ST), ST1553, was found to be susceptible to most of the antimicrobial agents tested. O-antigen serotyping of V. cholerae VCH20210731 revealed that it belonged to serotype Ob5. Interestingly, the ctxAB genes, which are typically associated with V. cholerae, were absent in VCH20210731. However, the strain possessed 25 other potential virulence genes, such as hlyA, luxS, hap, and rtxA. The resistome of V. cholerae VCH20210731 included several genes, including qnrVC4, crp, almG, and parE. Nevertheless, susceptibility testing demonstrated that the isolate was susceptible to most of the antimicrobial agents tested. Phylogenetic analysis indicated that the closest strain to VCH20210731 was strain 120 from Russia, differing by 630 single-nucleotide polymorphisms (SNPs). Our findings contribute to the understanding of the genomic epidemiological characteristics and antibiotic resistance mechanisms of this invasive bacterial pathogen. IMPORTANCE This study highlights the discovery of a novel ST1553 V. cholerae strain in China, providing valuable insights into the genomic epidemiology and global transmission dynamics of V. cholerae. It is important to note that clinical presentations of NOVC bacteremia can vary significantly, and the isolates demonstrate genetic diversity. Consequently, health care professionals and public health experts should remain vigilant about the potential for infection with this pathogen, particularly considering the elevated prevalence of liver disease in China.

Insights Into the Function and Clinical Application of HDAC5 in Cancer Management.

Histone deacetylase 5 (HDAC5) is a class II HDAC. Aberrant expression of HDAC5 has been observed in multiple cancer types, and its functions in cell proliferation and invasion, the immune response, and maintenance of stemness have been widely studied. HDAC5 is considered as a reliable therapeutic target for anticancer drugs. In light of recent findings regarding the role of epigenetic reprogramming in tumorigenesis, in this review, we provide an overview of the expression, biological functions, regulatory mechanisms, and clinical significance of HDAC5 in cancer.

E2F1 transactivates IQGAP3 and promotes proliferation of hepatocellular carcinoma cells through IQGAP3-mediated PKC-alpha activation.

For decades, E2F1 has been recognized as a retinoblastoma protein (RB) binding transcription factor that regulates the cell cycle. E2F1 binds preferentially to RB and accelerates the cell cycle in most cancer cells. However, it is thought that E2F1 modulates cell proliferation in other ways as well. Herein, it has been discovered that in pathological tissues derived from hepatocellular carcinoma (HCC) patients, E2F1 correlates positively with IQGAP3 and that both of these factors are highly expressed (N = 164, R = 0.6716). In addition, a high level of E2F1 or IQGAP3 predicted poor survival in HCC patients. Further study determined that E2F1 transactivates IQGAP3, the GTPase binding protein in MHCC-97H cells. Co-immunoprecipitation analysis indicated that IQGAP3 interacts with PKCδ and competitively inhibits the interaction between PKCδ and PKCα, resulting in phosphorylation of PKCα activation and promotion of cell proliferation. This study reveals that highly expressed E2F1 not only transactivates cell-cycle-related factors but also promotes HCC proliferation by activating the phosphorylation of PKCα.

Highly expressed histone deacetylase 5 promotes the growth of hepatocellular carcinoma cells by inhibiting the TAp63-maspin pathway.

Aberrant expression of histone deacetylases (HDACs) has been detected in a variety of cancers, which disrupts the balance between cell proliferation and apoptosis in favor of continuous growth. A previous study demonstrated that HDAC5 contributes to the proliferation of hepatocellular carcinoma (HCC) cells, but a clear understanding of the mechanism has not yet been provided. In the present work, we found that the levels of HDAC5 were significantly higher in HCC tissues and cells than in adjacent tissues and normal hepatic cells. In addition, knockdown of HDAC5 attenuated the proliferation of Hep3B and HepG2 cells. Through profiling the expressions of proliferation and apoptosis-related genes in Hep3B cells following HDAC5 knockdown, p63 and maspin were found obviously up-regulated in HDAC5-deprived cells compared with the control. Further investigations confirmed that HDAC5 knockdown induced TAp63 expression in HCC cells, accompanied with increased H3K9 acetylation at the TAp63 promoter. Overexpression of TAp63 led to proliferation inhibition by inducing cell cycle arrest. Additionally, TAp63 that was required for the maspin upregulation resulted from HDAC5 knockdown. Phenotype experiments showed that interrupting either TAp63 or maspin recovered the proliferative and tumorigenic capabilities of HCC cells with HDAC5 knockdown. Clinical analysis showed that HDAC5 was negatively correlated with TAp63 and maspin in HCC tissues. In addition, a high level of HDAC5 as well as a low level of TAp63 or maspin predicted poor survival in HCC patients. Taken together, this study proposes the existence of an aberrant HDAC5-TAp63-maspin pathway conferring HCC progression through proliferation induction, which suggests novel intervention targets for the disease.