Notes

Assistive Platform regarding Programmed Detection of All the Areas in Retinopathy associated with Prematurity Employing Strong Learning.
Rationale Considerable evidence suggests that breast cancer metastasis and recurrence occur due to emergence of cancer stem cells (CSCs). In our previous study, we designed a high-throughput siRNA screening platform that identifies inflammation genes involved in the regulation of cancer cell stemness. We reported that CCL16 protein decreases OCT4 expression and reduces the ALDH+ subpopulation. However, the mechanism by which CCL16 maintains stem cell-like properties remains unclear. Methods Tissue microarrays were used to evaluate CCL16 expression. Cancer stemness assays were performed in CCL16 knockdown and overexpressing cells in vitro and in a xenograft model in vivo. Human phosphokinase array, immunofluorescence and chromatin immunoprecipitation assays were performed to explore the underlying mechanism. Results We report that CCL16 was overexpressed in breast tumors and significantly correlated with clinical progression. We found that silencing CCL16 in MDA-MB-231 and BT549 cells diminished CSC properties including ALDH+ subpopulation, side population, chemo-resistance, and sphere formation. Furthermore, mice bearing CCL16-silenced MDA-MB-231 xenografts had lower tumorigenic frequency and developed smaller tumors. Exploration of the underlying mechanism found that CCL16 selects CCR2 to activate p-AKT/GSK3β signaling and facilitate β-catenin nuclear translocation. Further, CCL16 binds to the OCT4 promoter and promotes OCT4 expression. In addition, shRNAs targeting CCR2 and XAV939 targeting β-catenin abolished CCL16-mediated cancer stemness. Upstream, IL10 mediates STAT3 activation, which binds to the CCL16 promoter and enhances its expression. The STAT3-targeted inhibitor Stattic suppressed CCL16 expression in vitro and restrained tumor progression in vivo. selleck chemical Conclusions We identified a potential CSC regulator and suggest a novel mechanism for how CCL16 governs cancer cell stemness. We propose that CCL16 could be an effective target for breast cancer therapy.Phage therapy holds great promise for resolving the ever-worsening crisis of antibiotic resistance, but it also faces many challenges. One of the issues hampering phage therapy is the short blood residence time of bacteriophages. We have previously identified, through in vivo phage display, a blood circulation-prolonging peptide (BCP1) that was capable of significantly prolonging the blood retention time of a doxorubicin-loaded human ferritin nanocage, leading to enhanced therapeutic efficacy against tumors. Herein, we aimed to extend the application of BCP1 to anti-bacterial phage therapy. Methods A genetically engineered M13 phage, BCP1-BGL, that displayed the BCP-1 peptide and expressed the restriction endonuclease Bgl II, was constructed. Taking advantage of the fact that BCP1 harbors an RGD motif (a three amino-acid sequence Arg-Gly-Asp with the ability to bind to integrins) and exerts its circulation-prolonging activity primarily through interaction with platelets, we further designed and fabricated a bcations in phage therapy.Extracellular vesicles (EVs) are nanoscale extracellular vesicles derived from endocytosis that are crucial to intercellular communication. EVs possess natural biocompatibility and stability that allow them to cross biological membranes and that protect them from degradation. Recent studies have shown that EVs-mediated crosstalk between different cell types in the heart could play important roles in the maintenance of cardiac homeostasis and the pathogenesis of heart diseases. In particular, EVs secreted by different types of stem cells exhibit cardioprotective effects. However, numerous studies have shown that intravenously injected EVs are quickly cleared by macrophages of the mononuclear phagocyte system (MPS) and preferentially accumulate in MPS organs such as the liver, spleen, and lung. In this review, we discuss exosome biogenesis, the role of EVs in heart diseases, and challenges in delivering EVs to the heart. Furthermore, we extensively discuss the targeted delivery of EVs for treating ischemic heart disease. These understandings will aid in the development of effective treatment strategies for heart diseases.
Although significant progress has been made in understanding the mechanisms of steatosis and insulin resistance, the physiological functions of regulators in these processes remain largely elusive. Evidence has suggested that the glutamate/N-methyl-D-aspartic acid receptor (NMDAR) axis contributes to acute lung injury, pulmonary arterial hypertension, and diabetes, but the specific metabolic contribution of the glutamate/NMDAR axis is not clear. Here we provide data at the animal, cellular, and molecular levels to support the role of the glutamate/NMDAR axis as a therapeutic target for metabolic syndrome in obesity.
We examined the glutamate level in the obese mouse induced by a high-fat diet (HFD) for 12 weeks. To assess the role of NMDAR in insulin sensitivity and lipid metabolism, we tested the effects of Memantine (an NMDAR antagonist) and NMDA (an NMDAR agonist) on mice fed with HFD or standard chow diet. The
s NMDAR roles were analyzed in hepatocytes and potential mechanisms involved in regulatinf HFD-treated mice. The NMDAR blockade by Memantine decreased the susceptibility to insulin resistance and hepatic steatosis in obese mice. NMDA treatment for 6 months induced obesity in mice, characterized by hyperglycemia, hyperlipidemia, insulin resistance, and pathological changes in the liver. We provided in vitro evidence demonstrating that NMDAR activation facilitated metabolic syndrome in obesity through promoting lipid accumulation. NMDAR inhibition attenuated lipid accumulation induced by palmitic acid. Mechanistically, NMDAR activation impaired fatty acid oxidation by reducing PPARα phosphorylation and activity. The PPARα activity reduction induced by NMDAR activation was reversibly mediated by ERK1/2 signaling. Conclusion These findings revealed that targeting NMDAR might be a promising therapeutic strategy for metabolic syndrome in obesity.Rationale Acute lung injury (ALI)-recruited mononuclear phagocytes play a pivotal role in lung injury and repair. This study investigated the types of recruited mononuclear phagocytes and the immunotherapeutic effects of allograft mesenchymal stem cells (MSCs) in a mouse model of lipopolysaccharide (LPS)-induced ALI. Methods C57BL/6 mice were orotracheally instilled with LPS (20 mg/kg). Compact bone-derived MSCs were administered orotracheally 4 h after LPS inhalation. Mononuclear phagocytes recruited in the lung tissues were characterized at different timepoints by high-dimensional analysis including flow cytometry, mass cytometry, and single-cell RNA sequencing. Results Eight mononuclear phagocyte subsets recruited to LPS-challenged lungs were precisely identified. On day 3 after LPS administration, both Ly6ChiCD38+ and Ly6ClowCD38+ monocytes were recruited into acutely injured lungs, which was associated with increased secretion of neutrophil chemokines. Ly6ChiCD38+ monocytes differentiated into M1 macrophages on day 3, and subsequently differentiated into CD38+ monocyte-derived dendritic cells (mo-DCs) on day 7, while Ly6ClowCD38+ monocytes differentiated into CD11b+CD38+ DCs on day 7.
Here's my website: https://www.selleckchem.com/products/taurochenodeoxycholic-acid.html