Articles in 2019

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.

Transient receptor potential vanilloid 2 (TRPV2) plays a significant role in the onset and progression of heart failure. In this review, the authors summarize the recent findings on TRPV2 in cardiomyocytes and immune cells involved in the development of heart failure and discuss the current progress of drug development that is aimed at treating heart failure through targeting TRPV2.

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-Kit^W-sh/W-sh mice, BALB/c-Kit^W-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.

Transient receptor potential cation channel subfamily V (TRPV) can be overexpressed in breast cancer. TRPV channels play important roles in breast cancer cell proliferation, migration, and cell death as well as the tumor microenvironment and cancer-associated pain. This review provides an overview of TRPV channels in the context of breast cancer.

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).

The hedgehog pathway is pivotal in basal cell carcinoma and medulloblastoma development. Gorlin syndrome-derived, induced pluripotent stem cells (iPSCs) carrying a heterozygous mutation in PTCH1, a hedgehog target gene, exhibited high GLI1 expression and enhanced sensitivity to a hedgehog pathway inhibitor after neural differentiation. These iPSCs can serve as a model for hedgehog pathway-related tumors.

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⁺ (K_Ca3.1) 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.