Dielectrophoretic Capture of Cancer-Derived Small-Extracellular-Vesicle-Bound Janus Nanoparticles via Lectin-Glycan Interaction.

Glycosylation is closely related to cellular metabolism and disease progression. In particular, glycan levels in cancer cells and tissues increase during cancer progression. This upregulation of glycosylation in cancer cells may provide a basis for the development of new biomarkers for the targeting and diagnosis of specific cancers. Here, they developed a detection technology for pancreatic cancer cell-derived small extracellular vesicles (PC-sEVs) based on lectin-glycan interactions. Lectins specific for sialic acids are conjugated to Janus nanoparticles to induce interactions with PC-sEVs in a dielectrophoretic (DEP) system. PC-sEVs are selectively bound to the lectin-conjugated Janus nanoparticles (lectin-JNPs) with an affinity comparable to that of conventionally used carbohydrate antigen 19-9 (CA19-9) antibodies. Furthermore, sEVs-bound Lectin-JNPs (sEVs-Lec-JNPs) are manipulated between two electrodes to which an AC signal is applied for DEP capture. In addition, the proposed DEP system can be used to trap the sEVs-Lec-JNP on the electrodes. Their results, which are confirmed by lectin-JNPs using the proposed DEP system followed by target gene analysis, provide a basis for the development of a new early diagnostic marker based on the glycan characteristics of PC-sEVs. In turn, these novel detection methods could overcome the shortcomings of commercially available pancreatic cancer detection techniques.

Xelaglifam, a novel GPR40/FFAR1 agonist, exhibits enhanced ß-arrestin recruitment and sustained glycemic control for type 2 diabetes.

Xelaglifam, developed as a GPR40/FFAR1 agonist, induces glucose-dependent insulin secretion and reduces circulating glucose levels for Type 2 diabetes treatment. This study investigated the effects of Xelaglifam in comparison with Fasiglifam on the in vitro/in vivo anti-diabetic efficacy and selectivity, and the mechanistic basis. In vitro studies on downstream targets of Xelaglifam were performed in GPR40-expressing cells. Xelaglifam treatment exhibited dose-dependent effects, increasing inositol phosphate-1, Ca2+ mobilization, and ß-arrestin recruitment (EC50: 0.76 nM, 20 nM, 68 nM), supporting its role in Gq protein-dependent and G-protein-independent mechanisms. Despite a lack of change in the cAMP pathway, the Xelaglifam-treated group demonstrated increased insulin secretion compared to Fasiglifam in HIT-T15 ß cells under high glucose conditions. High doses of Xelaglifam (<30 mg/kg) did not induce hypoglycemia in Sprague-Dawley rats. In addition, Xelaglifam lowered glucose and increased insulin levels in diabetic rat models (GK, ZDF, OLETF). In GK rats, 1 mg/kg of Xelaglifam improved glucose tolerance (33.4 % and 15.6 % for the 1 and 5 h) after consecutive glucose challenges. Moreover, repeated dosing in ZDF and OLETF rats resulted in superior glucose tolerance (34 % and 35.1 % in ZDF and OLETF), reducing fasting hyperglycemia (18.3 % and 30 % in ZDF and OLETF) at lower doses; Xelaglifam demonstrated a longer-lasting effect with a greater effect on ß-cells including 3.8-fold enhanced insulin secretion. Co-treatment of Xelaglifam with SGLT-2 inhibitors showed additive or synergistic effects. Collectively, these results demonstrate the therapeutic efficacy and selectivity of Xelaglifam on GPR40, supportive of its potential for the treatment of Type 2 diabetes.

Role of Probiotics in Preventing Carbapenem-Resistant Enterobacteriaceae Colonization in the Intensive Care Unit: Risk Factors and Microbiome Analysis Study.

Older patients with multiple comorbidities often necessitate prolonged hospital stays and antibiotic treatment in the intensive care unit (ICU), leading to a rise in multidrug-resistant organisms like carbapenem-resistant Enterobacteriaceae (CRE). This study examined risk factors for carbapenem-resistant Enterobacteriaceae colonization in the ICU and assessed probiotics' preventive role. In this single-center, retrospective study, 9099 ICU patients were tested for stool CRE culture from March 2017 to April 2022. We excluded 136 patients with CRE colonization within one week post-admission and 26 who received probiotics before CRE colonization. Ultimately, 8937 CRE-negative patients were selected. Logistic analysis identified CRE colonization risk factors and evaluated probiotics' influence, including Saccharomyces boulardii or Lactobacillus rhamnosus, used by 474 patients (5.3%) in the ICU. Compared with data on initial admission, 157 patients (1.7%) had newly discovered CRE colonization before discharge. In a multivariate analysis, coronavirus disease 2019, the ICU, tube feeding, antibiotics such as aminoglycoside, extended-spectrum penicillin, stool vancomycin-resistance enterococci colonization, and chronic kidney disease were significantly associated with de novo CRE infection. However, probiotic use was negatively correlated with CRE infection. Managing risk factors and administering probiotics in the ICU may help prevent CRE colonization; large randomized prospective studies are needed.