In the present study, we investigated a novel signaling target in diabetic cardiomyopathy where inflammation induces caspase-1-dependent cell death, pyroptosis, involving Nek7-GBP5 activators to activate the NLRP3 inflammasome, destabilizes cardiac structure and neovascularization. Furthermore, we explored the therapeutic ability of bone morphogenetic protein-7 (BMP-7) to attenuate these adverse effects. C57BL/6J mice (n = 16 mice/group) were divided into control (200 mg/kg, 0.9% saline intraperitoneal injection, i.p.); Streptozotocin (STZ) and STZ-BMP-7 groups (STZ, 200 mg/kg, i.p. injection). After 6 weeks, heart function was examined with echocardiography, and mice were sacrificed. Immunostaining, Western blotting, H&E, and Masson’s trichrome staining was performed on heart tissues. STZ-induced diabetic cardiomyopathy significantly increased inflammasome formation (TLR4, NLRP3, Nek7, and GBP5), pyroptosis markers (caspase-1, IL-1β, and IL-18), inflammatory cytokines (IL-6 and TNF-α), MMP9, and infiltrationotential as a future therapy for diabetic patients.The cochaperone BCL2-associated athanogene 3 (BAG3), in complex with the heat shock protein HSPB8, facilitates mitotic rounding, spindle orientation, and proper abscission of daughter cells. BAG3 and HSPB8 mitotic functions implicate the sequestosome p62/SQSTM1, suggesting a role for protein quality control. However, the interplay between this chaperone-assisted pathway and the mitotic machinery is not known. Here, we show that BAG3 phosphorylation at the conserved T285 is regulated by CDK1 and activates its function in mitotic cell shape remodeling. BAG3 phosphorylation exhibited a high dynamic at mitotic entry and both a non-phosphorylatable BAG3T285A and a phosphomimetic BAG3T285D protein were unable to correct the mitotic defects in BAG3-depleted HeLa cells. We also demonstrate that BAG3 phosphorylation, HSPB8, and CDK1 activity modulate the molecular assembly of p62/SQSTM1 into mitotic bodies containing K63 polyubiquitinated chains. These findings suggest the existence of a mitotically regulated spatial quality control mechanism for the fidelity of cell shape remodeling in highly dividing cells.Exercise itself is fundamental for good health, and when practiced regularly confers a myriad of metabolic benefits in a range of tissues. These benefits are mediated by a range of adaptive responses in a coordinated, multi-organ manner. The continued understanding of the molecular mechanisms of action which confer beneficial effects of exercise on the body will identify more specific pathways which can be manipulated by therapeutic intervention in order to prevent or treat various metabolism-associated diseases. This is particularly important as exercise is not an available option to all and so novel methods must be identified to confer the beneficial effects of exercise in a therapeutic manner. This review will focus on key emerging molecular mechanisms of mitochondrial biogenesis, autophagy and mitophagy in selected, highly metabolic tissues, describing their regulation and contribution to beneficial adaptations to exercise.Autophagy is a physiological degradation process that removes unnecessary or dysfunctional components of cells. It is important for normal cellular homeostasis and as a response to a variety of stresses, such as nutrient deprivation. Defects in autophagy have been linked to numerous human diseases, including cancers. Cancer cells require autophagy to migrate and to invade. Here, we study the intracellular topology of this interplay between autophagy and cell migration by an interdisciplinary live imaging approach which combines micro-patterning techniques and an autophagy reporter (RFP-GFP-LC3) to monitor over time, during directed migration, the back-front spatial distribution of LC3-positive compartments (autophagosomes and autolysosomes). Moreover, by exploiting a genetically controlled cell model, we assessed the impact of transformation by the Ras oncogene, one of the most frequently mutated genes in human cancers, which is known to increase both cell motility and basal autophagy. Static cells displayed an isotropic distribution of autophagy LC3-positive compartments. Directed migration globally increased autophagy and polarized both autophagosomes and autolysosomes at the front of the nucleus of migrating cells. In Ras-transformed cells, the front polarization of LC3 compartments was much less organized, spatially and temporally, as compared to normal cells. This might be a consequence of altered lysosome positioning. In conclusion, this work reveals that autophagy organelles are polarized toward the cell front during migration and that their spatial-temporal dynamics are altered in motile cancer cells that express an oncogenic Ras protein.The phosphatidylinositol 3-kinase (PI3K)-dependent signaling pathway is aberrantly activated in psoriatic lesions and contributes to disease pathogenesis. Among PI3Ks enzymes, PI3Kα, β, and δ isoforms are known to bind the p85 regulatory subunit and mediate activation of AKT and other downstream effectors. In this study, we deepened our understanding of the expression and function of PI3Kδ in skin lesions of patients affected by psoriasis. For the first time, we found that PI3Kδ is overexpressed in psoriatic plaques, and its expression is not only confined to infiltrating immune cells but also accumulates in proliferating keratinocytes of the epidermal basal layer. We investigated the function of PI3Kδ in psoriatic skin by evaluating the impact of seletalisib, a newly developed selective PI3Kδ inhibitor, in both in vitro and in vivo experimental models of psoriasis. Of note, we found that PI3Kδ sustains keratinocyte hyperproliferation and impaired terminal differentiation induced by IL-22, as well as induces epithelial inflammation and resistance to apoptosis mediated by TNF-α in human keratinocytes. Mechanistically, PI3Kδ promotes PDK1 phosphorylation and signals through AKT-dependent or -independent pathways. It is worth mentioning that PI3Kδ inhibition by seletalisib attenuates the severity of psoriasiform phenotype induced in the Imiquimod-induced mouse model of psoriasis by restoring the physiological proliferation and differentiation programs in epidermal keratinocytes and contrasting the cutaneous inflammatory responses. Therefore, we suggest PI3Kδ as a potential topically druggable target in psoriasis and skin diseases characterized by epidermal hyperproliferation and skin inflammation.Oxidative damage to retinal pigment epithelial (RPE) has been identified as one of the major regulatory factors in the pathogenesis of age-related macular degeneration (AMD). Catalpol is an iridoid glucoside compound that has been found to possess potential antioxidant activity. In the present study, we aimed to investigate the protective effect of catalpol on RPE cells under oxidative stress and to elucidate the potential molecular mechanism involved. We found that catalpol significantly attenuated hydrogen peroxide (H2O2)-induced cytotoxicity, G0/G1 phase cell cycle arrest, and apoptosis in RPE cells. The overproduction of reactive oxygen species (ROS) and malondialdehyde (MDA) stimulated by oxidative stress and the corresponding reductions in antioxidant glutathione (GSH) and superoxide dismutase (SOD) levels were largely reversed by catalpol pretreatment. Moreover, catalpol pretreatment markedly activated the expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and its downstream antioxidant enzymes, catalase (CAT), heme oxygenase-1 (HO-1), and NADPH dehydrogenase (NQO1). It also increased the expression levels of cyclin E, Bcl-2, cyclin A, and cyclin-dependent kinase 2 (CDK2) and decreased the expression levels of Bax, Fas, cleaved PARP, p-p53, and p21 cleaved caspase-3, 8, and 9. The oxidative stress-induced formation of the Keap1/Nrf2 complex in the cytoplasm was significantly blocked by catalpol pretreatment. These results indicate that catalpol protected RPE cells from oxidative stress through a mechanism involving the activation of the Keap1/Nrf2/ARE pathways and the inactivation of oxidative stress-mediated pathways of apoptosis.Nonalcoholic fatty liver disease (NAFLD) is one of the most common and increasing liver diseases worldwide. NAFLD is a term that involves a variety of conditions such as fatty liver, steatohepatitis, or fibrosis. Gut microbiota and its products have been extensively studied because of a close relation between NAFLD and microbiota in pathogenesis. In the progression of NAFLD, various microbiota-related molecular and cellular mechanisms, including dysbiosis, leaky bowel, endotoxin, bile acids enterohepatic circulation, metabolites, or alcohol-producing microbiota, are involved. Currently, diagnosis and treatment techniques using these mechanisms are being developed. In this review, we will introduce the microbiota-related mechanisms in the progression of NAFLD and future directions will be discussed.As the main derivative of paclitaxel, 7-Epitaxol is known to a have higher stability and cytotoxicity. However, the anticancer effect of 7-Epitaxol is still unclear. The purpose of this study was to explore the anticancer effects of 7-Epitaxol in squamous cell carcinoma of the head and neck (HNSCC). Our study findings revealed that 7-Epitaxol potently suppressed cell viability in SCC-9 and SCC-47 cells by inducing cell cycle arrest. Flow cytometry and DAPI staining demonstrated that 7-Epitaxol treatment induced cell death, mitochondrial membrane potential and chromatin condensation in OSCC cell lines. The compound regulated the proteins of extrinsic and intrinsic pathways at the highest concentration, and also increased the activation of caspases 3, 8, 9, and PARP in OSCC cell lines. Interestingly, a 7-Epitaxol-mediated induction of LC3-I/II expression and suppression of p62 expression were observed in OSCC cells lines. Furthermore, the MAPK inhibitors indicated that 7-Epitaxol induces apoptosis and autophagy marker proteins (cleaved-PARP and LC3-I/II) by reducing the phosphorylation of ERK1/2. In conclusion, these findings indicate the involvement of 7-Epitaxol in inducing apoptosis and autophagy through ERK1/2 signaling pathway, which identify 7-Epitaxol as a potent cytotoxic agent in HNSCC.Conventional wisdom is that Sprouty2 (SPRY2), a suppressor of Receptor Tyrosine Kinase (RTK) signaling, functions as a tumor suppressor and is downregulated in many solid tumors. We reported, for the first time, that increased expression of SPRY2 augments cancer phenotype and Epithelial-Mesenchymal-Transition (EMT) in colorectal cancer (CRC). In this report, we assessed epigenetic DNA modifications that regulate SPRY2 expression in CRC. A total of 4 loci within SPRY2 were evaluated for 5mC using Combined Bisulfite Restriction Analysis (COBRA). Previously sequenced 5hmC nano-hmC seal data within SPRY2 promoter and gene body were evaluated in CRC. Combined bioinformatics analyses of SPRY2 CRC transcripts by RNA-seq/microarray and 450K methyl-array data archived in The Cancer Genome Atlas (TCGA) and GEO database were performed. SPRY2 protein in CRC tumors and cells was measured by Western blotting. Increased SPRY2 mRNA was observed across several CRC datasets and increased protein expression was observed among CRC patient samples.