Tumor-infiltrating T lymphocytes: A promising immunotherapeutic target for preventing immune escape in cholangiocarcinoma.

Cholangiocarcinoma (CCA) is becoming more common and deadly worldwide. Tumor-infiltrating T cell subtypes make distinct contributions to the immune system; collectively, they constitute a significant portion of the tumor microenvironment (TME) in CCA. By secreting cytokines and other chemicals, regulatory T cells (Tregs) decrease activated T cell responses, acting as immunosuppressors. Reduced CD8+ T cell activation results in stimulating programmed death-1 (PD-1), which undermines the immunological homeostasis of T lymphocytes. On the other hand, cancer cells are eliminated by activated cytotoxic T lymphocyte (CTL) through the perforin-granzyme or Fas-FasL pathways. Th1 and CTL immune cell infiltration into the malignant tumor is also facilitated by γδ T cells. A higher prognosis is typically implied by CD8+ T cell infiltration, and survival is inversely associated with Treg cell density. Immune checkpoint inhibitors, either singly or in combination, provide novel therapeutic strategies for CCA immunotherapy. Furthermore, it is anticipated that immunotherapeutic strategies-such as the identification of new immune targets, combination treatments involving several immune checkpoint inhibitors, and chimeric antigen receptor-T therapies (CAR-T)-will optimize the effectiveness of anti-CCA treatments while reducing adverse effects.

Single-atom nanozymes shines diagnostics of gastrointestinal diseases.

Various clinical symptoms of digestive system, such as infectious, inflammatory, and malignant disorders, have a profound impact on the quality of life and overall health of patients. Therefore, the chase for more potent medicines is both highly significant and urgent. Nanozymes, a novel class of nanomaterials, amalgamate the biological properties of nanomaterials with the catalytic activity of enzymes, and have been engineered for various biomedical applications, including complex gastrointestinal diseases (GI). Particularly, because of their distinctive metal coordination structure and ability to maximize atom use efficiency, single-atom nanozymes (SAzymes) with atomically scattered metal centers are becoming a more viable substitute for natural enzymes. Traditional nanozyme design strategies are no longer able to meet the current requirements for efficient and diverse SAzymes design due to the diversification and complexity of preparation processes. As a result, this review emphasizes the design concept and the synthesis strategy of SAzymes, and corresponding bioenzyme-like activities, such as superoxide dismutase (SOD), peroxidase (POD), oxidase (OXD), catalase (CAT), and glutathione peroxidase (GPx). Then the various application of SAzymes in GI illnesses are summarized, which should encourage further research into nanozymes to achieve better application characteristics.

Ferroptosis exacerbates hyperlipidemic acute pancreatitis by enhancing lipid peroxidation and modulating the immune microenvironment.

Abnormal activation of ferroptosis worsens the severity of acute pancreatitis and intensifies the inflammatory response and organ damage, but the detailed underlying mechanisms are unknown. Compared with other types of pancreatitis, hyperlipidemic acute pancreatitis (HLAP) is more likely to progress to necrotizing pancreatitis, possibly due to peripancreatic lipolysis and the production of unsaturated fatty acids. Moreover, high levels of unsaturated fatty acids undergo lipid peroxidation and trigger ferroptosis to further exacerbate inflammation and worsen HLAP. This paper focuses on the malignant development of hyperlipidemic pancreatitis with severe disease combined with the core features of ferroptosis to explore and describe the mechanism of this phenomenon and shows that the activation of lipid peroxidation and the aberrant intracellular release of many inflammatory mediators during ferroptosis are the key processes that regulate the degree of disease development in patients with HLAP. Inhibiting the activation of ferroptosis effectively reduces the intensity of the inflammatory response, thus reducing organ damage in patients and preventing the risk of HLAP exacerbation. Additionally, this paper summarizes the key targets and potential therapeutic agents of ferroptosis associated with HLAP deterioration to provide new ideas for future clinical applications.

Enantioselective effects of chiral fragrance carvone (L- and D-carvone) on the physiology, oxidative damage, synthesis, and release of microcystin-LR in Microcystis aeruginosa.

Carvone is a widely used chiral fragrance with two isomers (L-carvone and D-carvone). D-carvone smells like a caraway, whereas L-carvone smells like mint. Carvone imposes a potential burden on the aquatic ecosystem. However, the enantioselective toxic effect of carvone enantiomers on cyanobacteria remains unknown. This study aims to investigate the effects of L- and D-carvone on the physiological processes and related gene transcription (phoU, rbcL, and mcyH) in M. aeruginosa. Results showed that in the presence of L- and D-carvone, the oxidative damage and inhibitory effects on growth occurred in a concentration-dependent manner. The contents of chlorophyll a and protein and the rbcL transcription level were inhibited in M. aeruginosa. In addition, intracellular adenosine triphosphate (ATP) was heavily depleted because of various biological processes, including growth, oxidation reactions, and gene regulation. Meanwhile, L- and D-carvone stimulated the production and release of MC-LR and upregulated the expression level of the MC-LR-related gene mcyH. Intracellular MC-LR likely leaked to the water body under L-carvone exposure, posing a potential threat to the water environment. This study indicated that L- and D-carvone can regulate the physiological and metabolic activity of M. aeruginosa and show enantioselective toxic effects. The findings will also provide important insights into the influence of chiral fragrance on cyanobacterial blooms. Furthermore, this study will guide the safe application of chiral fragrance as personal care products.

The monthly variation tendency of microcystin-LR levels in the Huangpu River (China) by applications of ELISA and HPLC.

In this study, the contents of microcystin-LR (MC-LR) of Microcystis aeruginosa cultures in the laboratory and natural water samples from the Huangpu River in different seasons were detected through enzyme-linked immunosorbent assay (ELISA) and high-performance liquid chromatography (HPLC), respectively. Excellent correlation between the two methods was obtained (R2 > 0.99). ELISA was a reliable and simple method with high reproducibility (coefficient of variation < 25%) and satisfactory recovery for the monitoring of low levels of MC-LR. MC-LR concentrations in Huangpu River varied with the seasonal variation, which peaked in August with the temperature over 30 °C and then gradually declined with the decreasing temperature after August. The highest MC-LR concentration in the Huangpu River was below the WHO drinking water quality standard (1 µg/L). These results indicated that warm temperature accelerated the MC-LR synthesis and release, and it is necessary to regularly monitor the MC-LR levels, especially during the high algae period in summer. ELISA can be applied to detect the low levels of MC-LR in the field without complex treatment, avoiding the samples from denaturation and degradation during the transportation. Hence, ELISA is a better alternative of HPLC when HPLC is unavailable, especially when rapid testing is required in routine MC-LR analysis.