PAGE-B incorporating moderate HBV DNA levels predicts risk of HCC among patients entering into HBeAg-positive chronic hepatitis B.

BACKGROUND & AIMS: Recent studies reported that moderate HBV DNA levels are significantly associated with hepatocellular carcinoma (HCC) risk in hepatitis B e antigen (HBeAg)-positive, non-cirrhotic patients with chronic hepatitis B (CHB). We aimed to develop and validate a new risk score to predict HCC development using baseline moderate HBV DNA levels in patients entering into HBeAg-positive CHB from chronic infection. METHODS: This multicenter cohort study recruited 3,585 HBeAg-positive, non-cirrhotic patients who started antiviral treatment with entecavir or tenofovir disoproxil fumarate at phase change into CHB from chronic infection in 23 tertiary university-affiliated hospitals of South Korea (2012-2020). A new HCC risk score (PAGED-B) was developed (training cohort, n = 2,367) based on multivariable Cox models. Internal validation using bootstrap sampling and external validation (validation cohort, n = 1,218) were performed. RESULTS: Sixty (1.7%) patients developed HCC (median follow-up, 5.4 years). In the training cohort, age, gender, platelets, diabetes and moderate HBV DNA levels (5.00-7.99 log10 IU/ml) were independently associated with HCC development; the PAGED-B score (based on these five predictors) showed a time-dependent AUROC of 0.81 for the prediction of HCC development at 5 years. In the validation cohort, the AUROC of PAGED-B was 0.85, significantly higher than for other risk scores (PAGE-B, mPAGE-B, CAMD, and REAL-B). When stratified by the PAGED-B score, the HCC risk was significantly higher in high-risk patients than in low-risk patients (sub-distribution hazard ratio = 8.43 in the training and 11.59 in the validation cohorts, all p <0.001). CONCLUSIONS: The newly established PAGED-B score may enable risk stratification for HCC at the time of transition into HBeAg-positive CHB. IMPACT AND IMPLICATIONS: In this study, we developed and validated a new risk score to predict hepatocellular carcinoma (HCC) development in patients entering into hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) from chronic infection. The newly established PAGED-B score, which included baseline moderate HBV DNA levels (5-8 log10 IU/ml), improved on the predictive performance of prior risk scores. Based on a patient's age, gender, diabetic status, platelet count, and moderate DNA levels (5-8 log10 IU/ml) at the phase change into CHB from chronic infection, the PAGED-B score represents a reliable and easily available risk score to predict HCC development during the first 5 years of antiviral treatment in HBeAg-positive patients entering into CHB. With a scoring range from 0 to 12 points, the PAGED-B score significantly differentiated the 5-year HCC risk: low <7 points and high ≥7 points.

Microfluidic Designing Microgels Containing Highly Concentrated Gold Nanoparticles for SERS Analysis of Complex Fluids.

Surface-enhanced Raman scattering (SERS) is one of the most promising methods to detect small molecules for point-of-care analysis as it is rapid, nondestructive, label-free, and applicable for aqueous samples. Here, microgels containing highly concentrated yet evenly dispersed gold nanoparticles are designed to provide SERS substrates that simultaneously achieve contamination-free metal surfaces and high signal enhancement and reproducibility. With capillary microfluidic devices, water-in-oil-in-water (W/O/W) double-emulsion drops are prepared to contain gold nanoparticles and hydrogel precursors in innermost drop. Under hypertonic condition, water is selectively pumped out from the innermost drops. Therefore, gold nanoparticles are gently concentrated without forming aggregates, which are then captured by hydrogel matrix. The resulting microgels have a concentration of gold nanoparticles ≈30 times higher and show Raman intensity two orders of magnitude higher than those with no enrichment. In addition, even distribution of gold nanoparticles results in uniform Raman intensity, providing high signal reproducibility. Moreover, as the matrix of the microgel serves as a molecular filter, large adhesive proteins are rejected, which enables the direct detection of small molecules dissolved in the protein solution. It is believed that this advanced SERS platform is useful for in situ detection of toxic molecules in complex mixtures such as biological fluids, foods, and cosmetics.

The influences of weaning age and weight on carcass traits and meat quality of pigs.

The purpose of this study was to establish the effects of weaning age and weight on pigs, and their interaction with carcass traits and meat quality. A total of 468 piglets were obtained from 57 sows and four boars and grouped by age at weaning (D21, 18-24 days; D28, 25-32 days). Each weaning group was subdivided into three weight groups (L, M and H) according to weaning weight. The D28 group had heavier carcass weight, redness and yellowness, but had lower marbling scores and less drip loss than the D21 group (P < 0.05). The pigs with a light weight at weaning had higher carcass weights and lower yellowness than did pigs with a medium or heavy weight at weaning (P < 0.05). Weaning age was found to have a negative correlation with drip loss, while weaning weight was negatively correlated with carcass weight and drip loss (P < 0.05). We concluded that carcass and meat quality traits in pigs were significantly related to their age and weight at weaning. Therefore, we find that piglet weaning age and weight are no less important than post-weaning growth performance and behavior, with regard to carcass traits and meat quality.

TIS21(/BTG2/PC3) inhibits interleukin-6 expression via downregulation of STAT3 pathway.

Cancer cell growth was increased when co-cultured with fibroblasts, however, no effect was observed when co-cultured with TIS21-overexpressed fibroblast. Therefore, the role of TIS21 played in cancer microenvironment was investigated. TIS21 decreased interleukin-6 (IL-6) expression in human dermal fibroblast (HDF). Adenoviral transduction of TIS21 gene to HDF decreased the secretion of IL-6, whereas knockdown of the gene increased IL-6 expression. Furthermore, TIS21 overexpression inhibited STAT3 binding to IL-6 promoter region as well as JAK2-STAT3 signaling by inhibiting reactive oxygen species (ROS) generation by being localized in mitochondria. Mitochondria-target TIS21 (MT-TIS21) also inhibited IL-6 expression by downregulating STAT3 phosphorylation, whereas NF-κB pathway was not influenced by TIS21 expression. These results indicate that TIS21 negatively regulated cancer cell growth by inhibiting IL-6 expression through downregulation of STAT3 activation.

Gankyrin is frequently overexpressed in breast cancer and is associated with ErbB2 expression.

Gankyrin is a subunit of the 26S proteasome, and has been known to degrade p53 and retinoblastoma protein and promote the tumorigenicity and metastasis in some malignancies. However, the role of gankyrin in breast cancer has not been explored. In this study, we investigated the expression of gankyrin in breast cancer and evaluated its effect on breast cancer. Representative cancer tissues including normal breasts from 60 patients with breast cancer were stained immunohistochemically for gankyrin, estrogen receptor, progesterone receptor, and ErbB2. We evaluated the relationship between gankyrin expression and clinicopathologic parameters or prognostic markers. We also attempted to clarify the mechanism of gankyrin involved in breast carcinogenesis by using MCF7 breast cancer cells. Gankyrin was weakly expressed in normal breast epithelial cells, however, tumor regions of 37/60 (61.7%) cases showed an overexpression of gankyrin. Gankyrin overexpression was associated with extensive intraductal carcinoma (p=0.014) and ErbB2 positivity (p=0.031) in invasive ductal carcinoma. In MCF7 breast cancer cells, downregulation of gankyrin was associated with a reduction of cell proliferation and tumorigenicity. In conclusion, gankyrin was identified in normal breasts and overexpressed in invasive breast cancers. The overexpression of gankyrin was associated with extensive intraductal carcinoma and ErbB2 expression in breast cancer.