I-Shou University

Oligonol (Olg) is an oligomerized polyphenol with a higher bioavailability and exhibits excellent antioxidant and anti-inflammatory properties.However, the effects and underlying mechanisms of Olg on bladder cancer are still largely unknown.The current study found that Olg markedly reduced the viability of bladder cancer cells through the induction of caspase-dependent apoptosis while exhibiting no noticeable toxicity to normal bladder cells.Combining Olg and cisplatin resulted in a synergistic cytotoxic effect on bladder cancer cells.Olg also inhibited cell migration and invasion by affecting the expression of E-cadherin, Snail, N-cadherin, and vimentin.These effects of Olg were significantly weaker in the NF-κB silencing cells, revealing that Olg may inhibit cell viability and motility by modulation of the TNF-α/NF-κB/Snail pathway in human bladder cancer cells.Olg acts against cancer cells and enhances cisplatin chemotherapy, and it holds great potential as an anticancer drug or complementary medicine for bladder cancer.

The current study aimed at investigating the efficacies of probiotics in alleviating the symptoms of irritability/emotional lability in individuals with a neurodevelopmental condition.

Randomized placebo-controlled trials were identified through searching major electronic databases from inception to December, 2023. The outcome of interests included improvements in the symptoms of irritability/emotional lability. Outcomes were quantitatively expressed as effect size (ES) based on standardized mean difference (SMD) with 95 % confidence interval (CI).

Seven studies with 1479 participants were included in this meta-analysis. The primary results revealed a significant improvement in the symptoms of irritability/emotional lability in individuals with neurodevelopmental conditions receiving probiotics compared with the placebos (SMD= -0.17, p = 0.03). Subgroup analyses demonstrated an association between a significant improvement in the symptoms of irritability/emotional lability and the use probiotics relative to placebos only in studies using multiple-strain probiotics (SMD=-0.19, p = 0.04, three studies with 452 participant) but not in those adopting single-strain regimens.

Our study supported the use of probiotics for alleviating the symptoms of irritability/emotional lability in individuals with neurodevelopmental conditions, mainly in those receiving multiple-strain probiotics as supplements. Nevertheless, the limited number of studies targeting irritability as their primary outcomes, and most did not investigate other confounding factors such as dietary habits or consumption of other nutritional supplements may impair the robustness of evidence. Our results, which were derived from a limited number of available trials, warrant further large-scale clinical investigations for verification.

Neutrophil dysregulation is implicated in a spectrum of inflammatory pathologies, suggesting the potential for targeting neutrophilic hyperactivation as a pharmacological strategy to manage inflammatory disorders. Building upon prior research where 2-thiolphenoxychromone derivatives were found to inhibit neutrophilic generation of superoxide anions, this study focused on exploring the structure-activity relationship (SAR) of different C2 bridging moieties and anti-inflammatory effects using bioisosteric replacements and scaffold-hopping approaches. Among various chemotypes, the N-(4-oxo-4H-chromen-2-yl)benzenesulfonamide derivatives emerged as robust inhibitors of both superoxide anion generation and elastase release from fMLF-activated human neutrophils, with IC₅₀ values in the single-digit micromolar range. Leveraging a forward pharmacology approach through computational prediction, compound 15b, a representative within this active molecular class, was discovered to exert these anti-inflammatory functions by blocking the p38α mitogen-activated protein kinase (MAPK) signaling cascade. This responded to a significant reduction in p38α MAPK and its downstream MK2 phosphorylation in activated neutrophils treated with 15b, with no apparent impact on extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and protein kinase B (AKT) phosphorylation levels. Additionally, this molecule exhibited inhibitory potential on intracellular reactive oxygen species (ROS) production, granule exocytosis, and chemotactic responses. Collectively, this study provides a novel skeleton for the development of inhibitors targeting the p38α MAPK pathway to mitigate neutrophilic inflammation.