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Citrate synthase is a core enzyme of tricarboxylic acid cycle, but the role of extra-mitochondrial CS (eCS) is less clear. eCS, abundant in the sperm head, triggers a first spike of egg Ca2+ oscillation in a phospholipase C zeta 1 -independent manner. Moreover, the fertility of eCs-knockout male mice dropped with age, indicating that eCS suppresses age-dependent sperm dysfunction by accelerating Ca2+ oscillation.
The S100A4/non-muscle myosin II-related signal cascade may contribute to the establishment and maintenance of epithelial mesenchymal transition/cancer stem cell properties, along with changes in cell proliferation and migration capability. These events may be initiated in carcinomatous components in uterine carcinosarcoma and lead to divergent sarcomatous differentiation.
The authors investigated the effects of castration-induced stromal remodeling and subsequent aberrant activation of epithelial–stromal interactions on reconstituted human prostate-like epithelium. They demonstrate that castration-induced stromal remodeling disrupted the reconstituted epithelial structure and induced the appearance of tenascin-C-positive fibroblasts, accompanied by activation of TGF-β signaling. The alteration of prostate stromal structure may be responsible for loss of the basement membrane and epithelial cell polarity.
This paper shows that TRPV4, a Ca2+-permeable nonselective cation channel, responds to extracellular environments to regulate oral squamous cell carcinoma cellular growth through CaMKII/AKT activity in vitro and in vivo.
This work examines the pathogenesis of angiotensin II (Ang-II)-induced muscle wasting. The authors show that Ang II increases NLRP3 inflammasome activation and mitochondrial reactive oxygen species generation. Additionally, PPAR-γ agonist can protect against Ang II-induced muscle wasting by preventing mitochondrial dysfunction (MtD), oxidative stress, and NLRP3 inflammasome activation. Targeting the PPAR-γ/MtD/NLRP3 inflammasome axis may therefore provide a therapeutic approach for muscle wasting.
The pathological significance of adipophilin (ADP), a primary protein component of lipid droplets, in cancer remains unclear. Here the authors show that high ADP expression in malignant melanoma is significantly associated with high proliferation and poor clinical prognosis. Cell-based assays supported the importance of ADP in tumor proliferation. They propose that ADP is a marker of aggressive melanoma with a lipogenic phenotype.
The authors show that 13-cis-retinoic acid (13cRA) has an antiproliferative effect in MYCN-amplified neuroblastoma cells. Poly (I:C) synergized with 13cRA enhances anti-apoptotic effects through innate immune signaling and mitochondrial stress response in 13cRA-responsive neuroblastoma cells. In addition, a combination of 13cRA/poly (I:C) induces neural differentiation and inhibits vessel formation, leading to retarded tumor growth.
The central nervous system damage in neonatal mice with EV-A71 infection may be caused by activated fetal cerebral astrocytes related to the immune response to the virus, including the disruption of the functioning of the brainstem through increased cytokines and neurotransmitters, rather than the typical cytopathic effect of viral infection.
Unlike C57BL/6-KitW-sh/W-sh mice, BALB/c-KitW-sh/W-sh mice exhibit wild-type levels of airway hyperresponsiveness and lung inflammation and remodeling in two models of allergic airway inflammation. By contrast, neither genotype exhibits signs of IgE-dependent passive cutaneous anaphylaxis. Thus, genetic background influences the apparent importance of mast cells in different models of allergic diseases.
This study shows that TRPC5 is an important negative regulator of retinal ganglion cell (RGC) axonal outgrowth and an important regulator of neurite remodeling. The authors hypothesize that TRPC5 senses abnormal intraocular pressure changes and contributes to the death of RGCs in disease. In glaucoma, for example, excessive Ca2+ entry through TRPC5 might induce dendritic and axonal remodeling, which could lead to cell death.
In this study, the authors show that arctigenin (AG) inhibits the inflammatory myeloid phenotype and alleviates heart damage after myocardial infarction. Mechanically, the transcription factor NFAT5 is involved in the cardioprotective effect of AG via the JAK/STAT and NF-κB signaling pathways.
The authors examined the mechanisms underlying the lineage switch from prostate adenocarcinoma (AdPC) to lethal neuroendocrine prostate cancer (NEPC). They identified SRY-related HMG-box gene 2 (SOX2) as a potential repressor that causes decreased expression of AdPC-specific genes in NEPC. The repressor role of SOX2 is attributed to the marked global hypomethylation of histone H3, which is driven by the activation of lysine-specific demethylase 1 (LSD1).
Vascular endothelial growth factor increases the profibrotic activity of atrial fibroblasts by activating the currents through transient receptor potential channels and intermediate-conductance calcium-activated K+ (KCa3.1) channels and by enhancing Ca2+ entry-induced phosphorylated Ca2+/calmodulin-dependent protein kinase II (CaMKII) signaling. These findings suggest a novel strategy targeting atrial myopathy and arrhythmofibrosis.
In the glioma microenvironment, tumor-associated macrophages secrete large amounts of chemokine (C-C motif) ligand 8 CCL8, which contributes to pseudopodia formation of glioblastoma cells and promotes progression of glioma. CCL8 induces invasion and stem-like traits of glioblastoma cells via CCR1/ CCR5-mediated ERK1/2 activation.
The authors evaluated the efficiency of different maternal diet interventions on reducing the risk for offspring nonalcoholic fatty liver disease due to maternal overnutrition. They found that that different maternal diet interventions prime the lipid metabolism differently via changes in lipogenesis and β-oxidation through insulin/AKT signaling and 5′ AMP-activated protein kinase signaling.
The expression of the stimulator of interferon genes (STING) in liver tissues is associated with the progression of human nonalcoholic fatty liver disease. Specifically, STING-expressing macrophages, in particular, monocyte-derived macrophages, are positively correlated with the degree of liver inflammation and/or fibrosis progression, which appeared to be mediated by the activation of the STING-TBK1 signaling pathway in macrophage.
In this paper, the authors found that conditional ablation of Shp2 in mouse K14-positive corneal epithelium (Shp2K14ce-cko) impairs corneal innervation and results in corneal epithelial thinning, which resembles neurotrophic keratopathy. Furthermore, the data indicate that Shp2 signaling plays a pivotal role in corneal epithelial homeostasis.
The authors investigated the potential mechanisms of interleukin-33 (IL-33) in the pathogenesis of ulcerative colitis. IL-33 was found to sustain mucosal inflammation by down-regulation of protective ABCG5/8 during recovery from colitis. These results may help to increase understanding regarding the IL-33-mediated pathogenesis of ulcerative colitis and potentially contribute to creation of a novel therapeutic strategy.
High expression of the transcription factor ETS2 plays important role in a mouse model of renal fibrosis and in TGF-β1-treated human tubular epithelial cells (HK2). ETS2 promotes TGF-β1-induces epithelial-to-mesenchymal transition (EMT) phenotypic inversion and the expression of EMT markers in HK2 cells by enhancing transcription of JUNB. These findings suggest that ETS2 could be a novel target for the prevention the progression of renal fibrosis.
The expression of HIP/PAP and its mouse counterpart, Reg3B, is markedly unregulated in fibrotic livers. Ectopic HIP/PAP potently protects from CCl4- and BDL-induced liver fibrosis in mice. This study shows that downregulation of TGF-βRII expression is one of the important underlying mechanisms for HIP/PAP in suppression of hepatic fibrosis.