Baicalin attenuated metabolic dysfunction-associated fatty liver disease by suppressing oxidative stress and inflammation via the p62-Keap1-Nrf2 signalling pathway in db/db mice.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is the main cause of chronic liver disease. Baicalin (Bai), a bioactive molecule found in Scutellaria baicalensis Georgi, possesses antioxidant and antiinflammatory properties. These activities suggest Bai could be a promising therapeutic agent against NAFLD; however, its specific effects and underlying mechanism are still not clear. This study aims to explore the effect of Bai to attenuate MAFLD and associated molecular mechanisms. Bai (50, 100 or 200 mg/kg) was orally administered to db/db mice with MAFLD for 4 weeks or db/m mice as the normal control. Bai markedly attenuated lipid accumulation, cirrhosis and hepatocytes apoptosis in the liver tissues of MAFLD mice, suggesting strong ability to attenuate MAFLD. Bai significantly reduced proinflammatory biomarkers and enhanced antioxidant enzymes, which appeared to be modulated by the upregulated p62-Keap1-Nrf2 signalling cascade; furthermore, cotreatment of Bai and all-trans-retinoic acid (Nrf2 inhibitor) demonstrated markedly weakened liver protective effects by Bai and its induced antioxidant and antiinflammatory responses. The present study supported the use of Bai in attenuating MAFLD as a promising therapeutic agent, and its strong mechanism of action in association with the upregulating the p62-keap1-Nrf2 pathway.

Research progress of a new immune checkpoint inhibitor T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain in anti-tumor immunotherapy / 中国热带医学

@#The T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) is an inhibitory receptor mainly expressed on active T-cells, or natural killer cells (NK cells) that activate negative stimulus signals in immune cells by combining with multiple ligands on the surface of target cells including tumor cells and infected cells. TIGIT plays an important regulatory role in the immune pathogenesis of tumors, viral infections and various autoimmune diseases by inhibiting the over activation of cells and the over secretion of proinflammatory cytokines. Recent researches show that TIGIT is highly expressed in T cells and NK cells of cancer patients, and is related to disease progression and poor clinical prognosis. Researchers try to enhance the activity of T cells or NK cells by blocking the binding of TIGIT and its ligand for therapeutic intervention. At present, there have been many reports about the use of anti-TIGIT monoclonal antibody treatment in different mouse tumor models leading to tumor regression, TIGIT has received extensive attention in cancer immunotherapy as a promising target for next generation cancer immunotherapy. Several clinical trials are currently evaluating the efficacy of anti-TIGIT monoclonal antibodies (mAbs) in patients with several cancers. The most advanced candidate, tiragolumab, has exhibited remarkable efficacy in programmed cell death ligand 1 (PD-L1)-positive non-small cell lung carcinoma (NSCLC) patients in phase Ⅱ clinical trials, in combination with PD-L1 blockade. However, the specific mechanism of TIGIT blockade remains to be fully elucidated.

Revealing unconventional host-guest complexation at nanostructured interface by surface-enhanced Raman spectroscopy.

Interfacial host-guest complexation offers a versatile way to functionalize nanomaterials. However, the complicated interfacial environment and trace amounts of components present at the interface make the study of interfacial complexation very difficult. Herein, taking the advantages of near-single-molecule level sensitivity and molecular fingerprint of surface-enhanced Raman spectroscopy (SERS), we reveal that a cooperative effect between cucurbit[7]uril (CB[7]) and methyl viologen (MV2+2I-) in aggregating Au NPs originates from the cooperative adsorption of halide counter anions I-, MV2+, and CB[7] on Au NPs surface. Moreover, similar SERS peak shifts in the control experiments using CB[n]s but with smaller cavity sizes suggested the occurrence of the same guest complexations among CB[5], CB[6], and CB[7] with MV2+. Hence, an unconventional exclusive complexation model is proposed between CB[7] and MV2+ on the surface of Au NPs, distinct from the well-known 1:1 inclusion complexation model in aqueous solutions. In summary, new insights into the fundamental understanding of host-guest interactions at nanostructured interfaces were obtained by SERS, which might be useful for applications related to host-guest chemistry in engineered nanomaterials.

Efficacy and safety of a novel submucosal injection solution for endoscopic resection in porcine models.

OBJECTIVE: A submucosal injection is usually required to improve the efficacy and safety of endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR). This study aimed to evaluate the performance of 3.3% sodium carboxymethyl starch (Na-CMS) solution, a novel submucosal injection solution, for ESD and EMR. METHODS: Na-CMS, normal saline (NS) and two commercially available agents (sigMAVisc and Eleview) were injected into the esophageal submucosa of randomly grouped pigs. The level of submucosal elevation was examined. Subsequently, ESD or EMR procedures using 3.3% Na-CMS or NS as submucosal injections were performed in the gastrointestinal tract of the pigs. RESULTS: Submucosal elevation was significantly higher and more sustained in the 3.3% Na-CMS group than in the controls (P < 0.05). The volume required for ESD or EMR was significantly lower in the 3.3% Na-CMS group than in the NS group (ESD: 12.21 ± 4.09 mL vs 28.25 ± 8.02 mL, P < 0.001; EMR: 3.99 ± 1.98 mL vs 7.15 ± 3.67 mL, P = 0.001). The ESD resection time was significantly shorter in the 3.3% Na-CMS group than in the NS group (16.58 ± 7.30 min vs 25.29 ± 11.89 min, P = 0.004). Hemorrhage after ESD in the 3.3% Na-CMS group was less severe than that in the NS group (P = 0.006). CONCLUSION: 3.3% Na-CMS is an effective, safe and low-cost submucosal injection solution and holds promise as preferable agent for submucosal injection in ESD and EMR procedures.