BackgroundHepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide owing to its high rates of metastasis and recurrence. The oncogene IQ motif-containing GTPase activating protein 3 (IQGAP3) is ubiquitously overexpressed in several human cancers, including liver, ovary, lung, large intestine, gastric, bone marrow, and breast malignancies and is involved in the invasion and metastasis of cancer cells. Therefore, we aimed to determine the biological role and molecular mechanism of IQGAP3 in HCC.MethodsWe used 120 archived clinical HCC samples, 9 snap-frozen HCC tumor tissues, and 4 normal liver tissues. Expression of IQGAP3 mRNA and protein in HCC cell lines (Hep3B, SMMC-7721, HCCC-9810, HepG2, BEL-7404, HCCLM3, QGY-7701, Huh7, and MHCC97H) and normal liver epithelial cells LO2 was examined by western blot, quantitative polymerase chain reaction, and immunohistochemistry. In addition, wound-healing and transwell matrix penetration assays were used to assess the migratory and invasive abilities of HCC cells, respectively.ResultsExpression of the IQGAP3 was robustly upregulated in HCC cells and tissues. High expression of IQGAP3 in HCC correlated with aggressive clinicopathological features and was an independent poor prognostic factor for overall survival. Furthermore, ectopic expression of IQGAP3 markedly enhanced HCC cell migration, invasion, and epithelial-to-mesenchymal transition (EMT) in vitro and promoted metastasis of orthotopic hepatic tumors in nude mice. Conversely, silencing endogenous IQGAP3 showed an opposite effect. Mechanistically, IQGAP3 promoted EMT and metastasis by activating TGF-β signaling.ConclusionsIQGAP3 functions as an important regulator of metastasis and EMT by constitutively activating the TGF-β signaling pathway in HCC. Our findings present new evidence of the role of IQGAP3 in EMT and metastasis, indicating its potential as a prognostic biomarker candidate and a therapeutic target against HCC.

To investigate the parameters associated with post-treatment recurrence of bacterial vaginosis (BV), clinical factors and vaginal microbiota were examined and analyzed for BV patients who received standard metronidazole therapy. The variables associated with BV recurrence included clinical factors of past BV history, use of intravaginal device, and D7 Nugent score as well as many microbial genera, with Lactobacillus, Enterococcus, Ureaplasma , and Aerococcus being the top contributors. Co-occurrence network analysis showed that whereas overwhelming majority of interbacterial interactions were positive, negative interactions were present and connected mostly to Lactobacillus, Enterococcus , and to a less extent Ureaplasma , suggesting the importance of interbacterial antagonism for treatment outcome. The patients who were cured and recurrent also exhibited clear differences in the species composition of Lactobacillus : although L. iners remained the dominant species at all time points, L. crispatus, L. gasseri , and L. jensenii displayed apparent differences in relative abundance between the cure and recurrent groups. Based on these results, we developed a 5-component panel comprising Enterococcus, L. crispatus, Ureaplasma, Aerococcus , and L. jensenii for predicting recurrence using D7 data and showed that it generated the specificity, sensitivity, and AUC values of 0.80, 0.66, and 0.73 for the discovery cohort and 0.80, 0.67, and 0.69 for the validation cohort. Our findings highlighted key microbial components for BV recurrence and suggested that they could be used to monitor the treatment outcome.

Little information is available for antibody levels against SARS‐CoV‐2 variants of concern induced by Omicron breakthrough infection and a third booster with an inactivated vaccine (InV) or Ad5‐nCoV in people with completion of two InV doses. Plasma was collected from InV pre‐vaccinated Omicron‐infected patients (OIPs), unvaccinated OIPs between 0 and 22 days, and healthy donors (HDs) 14 days or 6 months after the second doses of an InV and 14 days after a homogenous booster or heterologous booster of Ad5‐nCoV. Anti‐Wuhan‐, Anti‐Delta‐, and Anti‐Omicron‐receptor binding domain (RBD)‐IgG titers were detected using enzyme‐linked immunosorbent assay. InV pre‐vaccinated OIPs had higher anti‐Wuhan‐, anti‐Delta‐, and anti‐Omicron‐RBD‐IgG titers compared to unvaccinated OIPs. Anti‐Wuhan‐RBD‐IgG titers sharply increased in InV pre‐vaccinated OIPs 0–5 days postinfection (DPI), while the geometric mean titers (GMTs) of anti‐Delta‐ and anti‐Omicron‐RBD‐IgG were 3.3‐fold and 12.0‐fold lower. Then, the GMT of anti‐Delta‐ and anti‐Omicron‐RBD‐IgG increased to 35 112 and 28 186 during 11–22 DPI, about 2.6‐fold and 3.2‐fold lower, respectively, than the anti‐Wuhan‐RBD‐IgG titer. The anti‐Wuhan‐, anti‐Delta‐, and anti‐Omicron‐RBD‐IgG titers declined over time in HDs after two doses of an InV, with 25.2‐fold, 5.6‐fold, and 4.5‐fold declination, respectively, at 6 months relative to the titers at 14 days after the second vaccination. Anti‐Wuhan‐, anti‐Delta‐, and anti‐Omicron‐RBD‐IgG titers elicited by a heterologous Ad5‐nCoV booster were significantly higher than those elicited by an InV booster, comparable to those in InV pre‐vaccinated OIPs. InV and Ad5‐nCoV boosters could improve humoral immunity against Omicron variants. Of these, the Ad5‐nCoV booster is a better alternative.