interferon alpha 2b

Comparison of Peg-INF plus TDF versus TDF Monotherapy in Indeterminate-phase Chronic Hepatitis B Patients with High HBsAg levels, HBeAg-negative status, and Normal ALT Levels.

Liu Min M, Xiao An A, Bu Bing B, Zuo Lili L et al.

Chronic hepatitis B patients with baseline hepatitis B surface antigen (HBsAg) <1500 IU/mL are considered as the favorable population for achieving functional cure. This trial aimed to explore a treatment strategy to help the unfavorable population characterized by high HBsAg levels (>3000 IU/mL), hepatitis B e antigen-negative status, and normal alanine transaminase levels in the indeterminate phase (HBeIP), transition to the favorable group. In this investigator-initiated, open-label clinical trial, we randomly assigned participants aged 18 to 60 years with HBeIP characteristics to receive either tenofovir disoproxil fumarate (TDF) monotherapy (monotherapy group) or pegylated interferon alfa-2b (Peg-IFNα-2b) plus TDF (combination group). The primary endpoints were the HBsAg loss rate and the proportion of participants with HBsAg <1,500 IU/mL through week 96. From May 2021 to November 2023, we enrolled 263 participants, with 131 randomly assigned to the combination group and 132 to the monotherapy group. In the primary analysis, none of the 132 participants (0%) in the monotherapy group achieved HBsAg loss, compared with 10 of 131 (7.6%) in the combination group (P = 0.001). Through week 96, 48.9% (64/131) of participants in the combination group achieved HBsAg <1,500 IU/mL, and a reduction in HBsAg level greater than 1 log10 IU/mL between baseline and week 24 was an independent predictor of this endpoint (Odds Ratio = 16.957, 95% Confidence Interval: 3.002-95.797, P = 0.001). In contrast, only two participants (1.5%) in the monotherapy group achieved HBsAg <1,500 IU/mL. Compared with TDF monotherapy, combination therapy with Peg-IFNα-2b and TDF significantly improved both HBsAg <1,500 IU/mL and HBsAg loss rates in HBeIP patients.

qHBsAg Trajectories with Peg-IFNα-2b Add-on Therapy in Nucleos(t)ide Analog-experienced HBeAg-positive Chronic Hepatitis B.

Hu Kezhen K, Bi Yanzhen Y, Li Xiaoying X, Liu Xiangzhong X et al.

Phosphorylated Analogs of Paracetamol and Their Anti-Inflammatory Potential.

Cruz Osvaldo León de la OL, Gutiérrez-Rebolledo Gabriel Alfonso GA, Castro Carlos Zepactonal Gómez CZG, Juárez Ángel Daniel Campos ÁDC et al.

Paracetamol is a widely used analgesic and antipyretic agent; however, its use is limited by minimal anti-inflammatory activity and the risk of hepatotoxicity from prolonged oral use or in acute overdose. To address these limitations, four novel phosphorylated paracetamol analogs (2a-2d) were synthesized via a UV-radical methodology and evaluated through integrated in silico, in vitro, and in vivo for anti-inflammatory dermal approaches. Molecular docking suggested plausible binding interactions with COX-1 and COX-2 for all analogs. In vitro cytotoxicity assays in THP-1 cells showed that 2a and 2b did not affect cell viability at 100 μM over 24 h. In a TPA-induced acute ear edema model in CD1 male mice, 2a produced about 50% inhibition of edema at the lowest tested quantity (0.5 mg/ear), representing a fourfold potency advantage over indomethacin at the same amount, while 2b displayed significant anti-inflammatory and vasoregulatory activity at higher quantities. Computational ADME profiling indicated that all analogs satisfy Lipinski's drug-likeness criteria and exhibit low predicted hERG channel risk. These results support N-phosphorylation of 4-aminophenol as a viable strategy to improve the topical anti-inflammatory efficacy of paracetamol analogs.

Transcriptional regulation of ubiquitin specific peptidase 2b by farnesoid X receptor and its implications in the pathogenesis of hepatocellular carcinoma.

Ali Winifer W, Nadolny Christina C, Zhang Xinmu X, Chen Qiwen Q et al.

Farnesoid X receptor (FXR) signaling plays an important role in liver regeneration and carcinogenesis. Dysregulation of FXR signaling is linked to the pathogenesis of hepatocellular carcinoma (HCC) while FXR knockout mice spontaneously develop HCC as they age. Ubiquitin specific peptidase 2b (USP2b) is a deubiquitinating enzyme regulating protein stability and other activities. In our recent study, we found that USP2b was significantly downregulated in subjects with HCC and exhibited both tumor-promoting and tumor suppressive activity in a context-dependent manner. However, the mechanistic link between FXR signaling and USP2b and its implications in the pathogenesis of HCC remain to be determined. In this study, we revealed that USP2b was transcriptionally regulated by FXR. Activation of FXR significantly increased while antagonizing FXR reduced USP2b mRNA and protein expression in vitro and in vivo. Consistently, USP2b expression was significantly reduced in FXR knockout (FXR-KO) mice. Further investigation showed that USP2b was transcriptionally regulated by FXR in an isoform-specific manner, predominantly by FXRα2 but not FXRα1. The transcription starting sites (TSS) of USP2 isoforms were determined by 5'RACE, which leads to the identification of the USP2b-specific promoter. An FXR response element (FXRE) was identified in the USP2b promoter and functionally characterized. FXR directly bound to the FXRE in vitro and recruited to the USP2b promoter in intact cells and in vivo. Further study revealed that upon FXR activation, co-activator-associated arginine methyltransferase 1 (CARM-1) was significantly recruited to the human USP2b promoter while coactivators glutamate receptor-interacting protein 1 (GRIP-1) and peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) were significantly recruited to the mouse USP2b promoter. Over-expression of USP2b in FXR-KO mice significantly slowed down tumor growth with reduced tumor size while maintained comparable tumor numbers consistent with its tumor suppressive activity. In summary, this study demonstrated that USP2b was transcriptionally regulated by FXR in an isoform-dependent manner and USP2b played a tumor-suppressive role in the pathogenesis of FXR deficiency-induced HCC.