Second Affiliated Hospital of Wenzhou Medical University

The number of colorectal cancer (CRC) cases is rising among younger people, making it the second most common cancer worldwide. A pH-responsive hydrogel containing chitosan-based microbeads (BHCMB) is proposed for the targeted oral delivery of bevacizumab as a potential treatment for CRC. The structural and functional properties of BHCMB formulations were validated through characterization via FTIR and XPS analyses. Investigations of in vitro drug release by hydrogels have demonstrated their responsiveness to pH variations, facilitating accurate dosing in physiological conditions. The HCT-116 colorectal cancer cell line was utilized to assess the in vitro anti-cancer properties of BHCMB hydrogel formulations. At 50 µg/mL, BHCMB significantly reduced cell growth and caused apoptosis by damaging mitochondrial membranes and generating reactive oxygen species (ROS). The gene expression analysis revealed that BHCMB treatment significantly downregulated COX-2, IL-6, and BCL2 levels, while markedly upregulating p53 and Bax expression. Additionally, protein analysis in HCT-116 cells confirmed increased Bax and cleaved caspase-3 levels alongside reduced BCL2, indicating enhanced pro-apoptotic activity and potential anti-tumor effects in CRC. The in vivo study illustrates the efficacy of the BHCMB hydrogel in inhibiting CRC growth in a mice model. This research proposes an innovative pH-responsive hydrogel system for the oral administration of bevacizumab. The aim was to attain precise drug release at the colorectal tumor site, thereby enhancing apoptosis and effectively hindering CRC progression.

Biejia-Ruangan (BRG) has been approved in China as an antifibrotic traditional Chinese medicine for patients with chronic liver diseases; however, data on the reversal of hepatitis B-related cirrhosis by BRG are still limited.

To investigate the reversal effect of BRG in patients with hepatitis B-related cirrhosis.

Hepatitis B-related cirrhotic patients who received either entecavir (ETV) monotherapy or combination therapy with ETV and BRG for 7 years, were analysed. The primary endpoints included the regression of liver cirrhosis, liver histological improvement, and a significant reduction in the LSM value.

In total, 153 cirrhotic patients were enrolled, of whom 63 received ETV alone and 90 received both ETV and BRG. Ninety-four patients, of whom 39 received ETV monotherapy and 55 received both ETV and BRG, underwent liver biopsies at both the second and seventh years of treatment. Although the rate of liver cirrhosis regression did not significantly increase after two years of antifibrotic therapy in patients who received ETV and BRG combination therapy (43.3 % vs. 38.1 %, P = 0.217), the median LSM decreased significantly (8.3 kPa vs. 11.2 kPa, P = 0.041); after seven years of treatment, a significantly greater rate of liver cirrhosis regression was achieved (55.6 % vs. 38.1 %, P = 0.033), and the LSM value further decreased significantly (6.4 kPa vs. 11.0 kPa, P = 0.036).

BRG enhances the efficacy of ETV in reversing liver cirrhosis in patients with chronic HBV infection, but this reversal takes a longer time.

Nanoplastics and tire-derived chemicals are ubiquitous co-pollutants in aquatic environments, originating from road runoff and posing potential risks to vertebrate development through enhanced bioavailability and synergistic toxicity. Polystyrene nanoplastics (PS) can adsorb hydrophobic organics like the antioxidant N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD), acting as vectors that increase tissue accumulation and exacerbate oxidative stress, while 6PPD alone disrupts mitochondrial function and induces sublethal effects in exposed organisms. The vertebrate eye, with its direct environmental exposure and sensitive neural structures, is particularly vulnerable, yet the combined impact of PS and 6PPD on visual morphogenesis remains underexplored. Here we show that co-exposure to environmentally relevant concentrations of PS (1 mg L^-1) and 6PPD (0.1-0.8 mg L^-1) markedly potentiates ocular toxicity compared to individual exposures, manifesting as myopia-like malformations, increased cell death, and impaired phototaxis. We integrated phenotypic, histological, and multi-omics analyses using zebrafish embryos as a model. Our results show PS-enhanced bioaccumulation of 6PPD in ocular tissues, leading to severe lens and retinal damage, aberrant vascularization, disrupted myelination, and dysregulated pathways including serine proteolysis, retinoic acid metabolism, and ferroptosis-linked oxidative stress. These findings demonstrate nanoplastic-chemical interactions as an emerging threat to aquatic visual function, with implications for survival behaviors and broader ecosystem health under pervasive pollution.