Front Cover: The cover image is based on the Original Article Electric fields regulate cellular elasticity through intracellular Ca2+ concentrations by Kyungsook Kim et al., https://doi.org/10.1002/jcp.30417.

Nepetin showed a protective and therapeutic effect on the mouse osteoarthritis (OA) model and chondrocytes. This study indicated nepetin had a new potential therapeutic option in OA.

We report a cellular landscape of the human adrenal gland using single-cell RNA sequencing. At single-cell resolution, the transcriptomic map presents a comprehensive view of the human adrenal gland, which serves as a fundamental baseline description of this organ and paves a way for the further studies of adrenal diseases

Interleukin-17 (IL-17) and basic fibroblast growth factor (bFGF) manifest different effects on stemness features of stem cells from human exfoliated deciduous (SHEDs) and dental pulp stem cells (DPSCs) in terms of their proliferation and clonogenicity. While bFGF potentiate proliferative and clonogenic properties of both SHEDs and DPSCs, IL-17 similarly influences SHEDs, but not affecting adult counterparts, DPSCs. Moreover, both factors stimulate NANOG, OCT4, and SOX2 pluripotency markers expression in SHEDs and DPSCs and show comparable effects on their osteogenic differentiation, including stimulatory effect of IL-17 on early osteogenesis in contrast to strong inhibitory effect of bFGF.

First, we found that Nkx2-3 inhibited proliferation and migration in PDGF-BB-treated VSMCs and balloon-injured vessels. Second, we verified that Nkx2-3-promoted autophagy suppressed proliferation and migration of VSMCs in vivo and in vitro. Finally, we demonstrated that Nkx2-3 promoted autophagy via AMPK/mTOR signaling pathway.

Daunorubicin (DNR)-induced NOX4-mediated ROS generation activates p38 MAPK and inactivates Akt, which activates GSK3β by phosphorylation of Y216 and dephosphorylation of S9. GSK3β-mediated CREB phosphorylation promotes NOXA transcription in U937 and HL-60 cells. NOXA upregulation elicits MCL1 and BCL2L1 degradation, resulting in the activation of caspase-3 and apoptosis of U937 and HL-60 cells.

AMPK/mTOR downregulated autophagy enhances aberrant endometrial decidualization in folate-deficient pregnant mice.

This study describes how continual passage of neural stem cell (NSC), obtained from mouse embryo, results in the generation of immortal cells. Moreover, these transformed cells are capable to generate glioblastoma (GBM) when they are orthotopically injected in mice, and also heterotopic tumours when injected into the blood stream. The findings demonstrate that a suitable origin for GBM may be the dysregulated proliferation of NSC present in adult beings.

This study provided novel insights into the function and mechanism of action of M. tuberculosis effector PPE36 both at the cellular and animal level. We provides new research directions for the relationship between cytokine storm and tuberculosis treatment.

Chondrogenic progenitor cells (CPCs) may be used as an alternative source of cells with potentially superior chondrogenic potential compared to mesenchymal stem cells (MSCs) and could be exploited for future regenerative therapies targeting articular cartilage in degenerative diseases such as osteoarthritis (OA). In this study, we analysed the channelome of CPCs and MSCs using Affymetrix microarrays and quantitative reverse transcription-polymerase chain reaction. We examined the role of calcium-dependent potassium channels in CPCs and observed functional large-conductance calcium-activated potassium (BK) channels involved in the maintenance of the chondroprogenitor phenotype. We demonstrate that CPCs are a distinct cell population but are highly similar to MSCs in many respects.

The effects emodin, a plant-derived anthraquinone, on fibroblast activation and fibrosis induced by transforming growth factor beta 1 (TGF-β1) were evaluated. Treatment with emodin inhibited fibroblast activation and collagen expression induced by TGF-β1. Emodin also inhibited canonical TGF-β1 signaling while stimulating activation of p38 mitogen activated protein kinases.

We show changes in intracellular Ca²⁺ caused by electric fields (EFs), which induced gelsolin activation and F-actin content changes. This result demonstrates a series of processes in which external electrical stimulation conditions regulate cellular elasticity

Our study demonstrated NBP to show multiple therapeutic benefits after CA. It could reduce neuronal damage along with ultrastructural damage, apoptosis through the JNK/p38 pathway, inflammatory response through the NF-κB pathway, and neurotoxicity by reducing the PHF-Tau levels.

Lewis lung cancer-bearing mice displayed fragmented sleep, shortened wake phase, and prolonged sleep in the non-rapid eye movement (NREM) phase. 1,25(OH)2D3 treatment effectively saved the sleep quality of tumor-bearing mice. 1,25(OH)₂D₃ repressed tumor-induced neuroinflammation, enhanced neurotrophic factors, and 5-HT system. A molecular docking approach manifested the ability of 1,25(OH)2D3 to affect the activity of TPH2 and brain-derived neurotrophic factor (BDNF).

In human hepatocellular carcinoma (HCC) cells, forkhead box protein A2 (FOXA2) suppresses the migratory ability of tumor cells partially by promoting transcriptional expression of E-cadherin. O-GlcNAcylation, as a newfound posttranscriptional modification (PTM) of FOXA2, might stimulate migration of HCC cells by impairing FOXA2 stabilization and its transcriptional activity of downstream target gene E-cadherin.

Moderate mechanical stress rescues chondrocytes from interleukin-1β (IL-1β)-induced apoptosis by enhanced mitochondrial dynamics, including fission and fusion, while excessive stress induces an uncoupling of fission and fusion that breaks the balance and causes mitochondrial dysfunction and apoptosis.

Inflammatory pathway and disruption in glutamate homeostasis join at the level of the glia, resulting in various neurological disorders. However, the mechanisms by which glutamate homeostasis is altered during inflammation are yet to be understood. This is the first in vivo study to show that glutamate induced neuronal degeneration could be affected by the expression level and distribution of connexion (Cxs), pannexin-1 (Panx-1) and excitatory amino-acid transporters (EAATs). Intriguingly, nuclear factor-kB (NF-κB) activity directly correlated with the expression pattern of Cxs, Panx-1 and EAATs, suggesting that NFkB is an essential factor responsible for the glutamate induced neuronal degeneration. Targeting multiple pathways with combination of IκB Kinase (BAY-117082) and acetylcholinesterase (galantamine) inhibitors achieved strong anti-inflammatory synergistic effects with modulation of Cxs, Panx-1, and EAATs expressions and reduction of glutamate-induced neuronal cell loss. Our data provide a novel approaches to diagnosis and therapeutic strategies for several neurological disorders.

In this study, we aimed to uncover the mechanisms regulating AmeloD expression during tooth development. We found that TGF-β1 activates AmeloD transcription via ERK1/2 phosphorylation. Our findings provide new insights into the mechanisms that govern tooth development

Iron overload in adipocytes inhibits adiponectin synthesis, leading to decreases of serum adiponectin level, lipoprotein lipase (LPL), and hepatic lipase (HL) activities, thus induces elevation of serum triglyceride level.

Rnf213 gene, susceptibility gene for moyamoya disease, is highly expressed in dendritic cells. Dysregulation of Rnf213 gene lead to impaired antigen uptake, processing and presentation, leading to impaired T cell response.

Using the inducible Tet-on system, we found that regenerating family member 4 (Reg4) knockdown significantly impaired pancreatic regeneration after pancreatitis. Both acinar-to-ductal metaplasia (ADM) and the resolution of pancreatitis during regeneration were affected by Reg4 knockdown through regulating Notch activation.

The first study showing that ablation of TP53-induced glycolysis and apoptosis regulator (TIGAR) improves endothelial glycolytic function, mitochondrial respiration, and angiogenic capacity in vitro. Knockout of TIGAR promotes proangiogenic signaling, by increasing the expression of Ang-1, VEGF, and PFKFB3, and enhances myocardial angiogenesis and coronary flow reserve under pressure overload. Knockout of TIGAR preserves cardiac function by rebalancing angiogenesis with cardiac hypertrophy under stress.

This study found a new mechanism for the effect of vimentin on colorectal cancer (CRC) cells. The activator protein 1 transcription factor can combine with the vimentin promoter to regulate the expression of vimentin, and further affect the biological function of CRC cells and tumor growth.

2,4-DCP (2,4-dichlorophenol) is an environmental estrogen that is ubiquitously distributed in the environment and widely used to produce herbicides and pharmaceutical intermediates. Although 2,4-DCP is suspected to have endocrine disruption, the reproductive toxicity of 2,4-DCP in mammals has not been adequately assessed. We validated that the defects of fertilization participants and events caused by 2,4-DCP might be mediated by the increased level of reactive oxygen species-induced apoptosis of oocytes.

Disuse-induced muscle atrophy is associated with increased reactive oxygen species (ROS) from damaged mitochondria and mitophagy activity. However, the mitophagy activity status during disuse-induced muscle atrophy has been a subject of debate. In this study, we create a new line of mitophagy reporter mouse to examine the status of mitophagy activity in atrophic skeletal muscles. Our study concludes that disuse enhances mitophagy activity as well as ROS production in atrophic muscles.

Nuclear factor IB induces functional astrocytes from human pluripotent stem cell-derived neural precursor cells mimicking in vivo astrogliogenesis.

In this study, we demonstrated that autocrine basic fibroblast growth factor (bFGF) secretion is necessary for the proper barrier function of human brain capillary endothelial cells (BCECs), whereas exogenous bFGF in higher doses suppresses barrier resistance. Our findings demonstrate a dual role for bFGF in the regulation of BCEC barrier function

The FGF2/STAT3/YAP1 signaling pathway in the pathogenesis of tubulointerstitial fibrosis. In this pathway, FGF2 stimulates the activation of STAT3 and induces YAP1 transcription in renal tubular epithelial cells. Specifically, STAT3 directly binds to the promoter of YAP1 and regulates the YAP1 mRNA at the transcriptional level. The signaling is contributed to promote the occurrence and development of renal interstitial fibrosis.

The presence of collagen type I in normal human articular cartilage is controversial. Using fluorescent imaging and confocal microscopy of in situ femoral head chondrocytes and cell-associated collagen type I, we identified its presence around chondrocytes of both normal and abnormal morphology. Collagen type I levels increased markedly with mild cartilage degeneration and chondrocyte clustering. The results suggested the presence of mechanically-weak collagen type I in otherwise nondegenerate human cartilage which increased markedly in degenerate cartilage.

Comparing hepatopulmonary syndrome (HPS) and non-HPS models, we illustrated experimental HPS is associated with initial neutrophil recruitment and latter M2 macrophage accumulation. Neutrophil recruitment causes pulmonary vascular dilatation and hypoxemia. M2 macrophage accumulation, which induced by granulocyte-macrophage colony stimulating factor (GM-CSF) and monocyte chemoattractant protein 1 (MCP1), causes pulmonary fibrosis, and enhances vascular dilatation and hypoxemia.

Low concentrations of methylnaltrexone (MNTX) inhibits cancer cell proliferation, migration, and epithelial–mesenchymal transition of head and neck squamous cell carcinoma (HNSCC) via snail in vitro and in vivo. Targeting mu-opioid receptor (MOR-1) in patients with HNSCC could be used as an adjuvant treatment strategy.

Integrin β4 (ITGB4) is a structural adhesion molecule that is involved in the pathological progression of acute inflammatory diseases. We constructed airway epithelial cell-specific ITGB4 knockout (ITGB4^−/−) mice to study its role in acute lung injury (ALI). Overall, these data demonstrated a novel link between airway epithelial ITGB4 and the inflammatory response in lipopolysaccharide-induced ALI.

Our results provided evidence for the important roles of FASCIN on actin filaments for spindle migration and polar body extrusion in mouse oocyte meiosis.

The results in this study suggest that activation of Nrf2 by dimethyl itaconate can protect against pulmonary fibrosis via inhibiting TXNIP expression. Our study may provide a new therapeutic target and treatment approaches for pulmonary fibrosis.

The biosynthesis of many of the peptides involved in homeostatic control requires peptidylglycine α-amidating monooxygenase (PAM), an ancient, highly conserved copper- and ascorbate-dependent enzyme. The affinity of the purified monooxygenase for oxygen (K_m = 99 ± 19 μM) was consistent with this result. Putative hypoxia response elements occur in both human and mouse PAM, and hPAM has consistently been identified as one of the genes upregulated in response to hypoxia.

Yes-associated protein (YAP) and PDZ-binding motif (TAZ) have emerged as important regulators of pathologic fibroblast activation in fibrotic diseases, and agonism of the dopamine D1 G protein coupled receptor (GPCR) has proven effective in blocking YAP/TAZ and reducing fibrosis. Here we show essential roles for the cyclic adenosine monophosphate effectors EPAC1/2, the small GTPase RAP2c, and the serine/threonine kinase MAP4K7 as essential elements in the downstream signaling cascade linking GPCR agonism to LATS1/2-mediated YAP and TAZ phosphorylation and nuclear exclusion in fibroblasts.

Neuroblastoma (NB) is a common solid extracranial tumor developing in pediatric populations. Accuracy in clinical staging of the disease and assessment of the associated risks based on biological, clinical, surgical, and pathological criteria are of paramount importance for prognosis and to effectively plan therapeutic approaches. This review discusses the staging of NB and the biological and genetic features of the disease and several current therapies including targeted delivery of chemotherapy, novel radiation therapy, and immunotherapy for NB.

Our review is aimed to summarize the research outcomes which involves YAP/TAZ mediated mechanical-biochemical transduction and cell effects in OTM-relevant cells and tissues.

Emerging evidence suggests that long noncoding RNAs (lncRNAs) play an instrumental role in the regulation of intestinal stem cells, injury-induced regeneration, and initiation and progression of intestinal tumors. Here, we summarize the recently discovered lncRNAs during intestinal homeostasis, regeneration, and tumorigenesis. We further present lncRNAs as diagnostic and therapeutic markers in intestinal pathologies.

In the present review, we evaluated the published literature describing the use of signal transducer and activator of transcription 3 (STAT3) in the treatment of experimental and clinical sepsis. The information presented here may be useful for the design of future studies and may highlight the potential of STAT3 as a future biomarker and therapeutic target for sepsis.

Nucleophosmin (NPM1) is a well-known nucleocytoplasmic shuttling protein that performs several cellular functions such as ribosome biogenesis, chromatin remodeling, genomic stability, cell cycle progression, and apoptosis. In this review, we focus on the gene and protein structure of NPM1 and its physiological roles. Finally, we discuss the association of NPM1 with various types of cancer including solid tumors and leukemia.

The tumor microenvironment (TME) compose of tumor cells, nontumor cells, and extracellular matrix (ECM). HDL may play roles in cancer development by acting with both tumor and nontumor cells. In the submitted paper, we summarized clinical observations and carefully dissected possible mechanisms based on experimental data obtained in levels from cellular, organ, and genetically engineered animal models. A moderate increase in the level of HDL in vivo with consequent improvement of the function of HDL in the TME and induction of intracellular cholesterol efflux may be a promising strategy for cancer therapy.

This mini review article summarizes current progress on the interaction between adipose tissue and bone and the effects of EVs-AT on bone homeostasis and pathogenesis.