Maternal dexamethasone decreases the body length of the newborn. However, whether dexamethasone inhibits the development of the growth plate of the fetal long bone is still unknown. Here, we found that lengths of fetal femur and growth plate were both shorter in the fetuses with maternal dexamethasone (0.2 mg/kg.d from gestation day 9 to 20), with a decreased proteoglycan content of the growth plate

Metabolic reprograming is a hallmark of cancer, and the polyamine metabolic network is dysregulated in many cancers. Ornithine decarboxylase (ODC) is a rate‐limiting enzyme for polyamine synthesis in the polyamine metabolic network. In many cancer cells, ODC is over‐expressed, so this enzyme has been an attracting anti‐cancer drug target. In the catalysis axis (pathway), ODC converts ornithine to putrescine

Osteoarthritis (OA) is a degenerative joint disease, and inflammation within an arthritic joint plays a critical role in disease progression. Pro‐inflammatory cytokines, specifically IL‐1 and TNF‐α, induce aberrant expression of catabolic and degradative enzymes and inflammatory cytokines in OA and result in a challenging environment for cartilage repair and regeneration. MicroRNAs (miRNAS) are small

Phospholipase Cβ1 is activated by Gαq to generate calcium signals in response to hormones and neurotransmitters. Besides carrying out this plasma membrane function, PLCβ1 has a cytosolic population that helps to drive the differentiation of PC12 cells by inhibiting a nuclease that promotes RNA‐induced silencing (C3PO). Here, we show that down‐regulating PLCβ1 or reducing its cytosolic population by

Dementia is one of the most pressing health care issues of this century. As no curative treatment for dementia exists, research efforts are growing to identify effective lifestyle interventions to prevent or delay onset. One such promising strategy that promotes cognitive and brain health is engaging in physical exercise. However, current exercise recommendations are imprecise. To advance the potential

Cancer cells rely on several metabolic pathways such as lipid metabolism to meet the increase in energy demand, cell division, and growth and successfully adapt to challenging environments. Fatty acid synthesis is therefore commonly enhanced in many cancer cell lines. Thus, relevant efforts are being made by the scientific community to inhibit the enzymes involved in lipid metabolism to disrupt cancer

Few studies have explored the mechanisms coupling estrogen signals to metabolic demand in endothelial cells. We recently showed that 17β‐estradiol (E2) triggers angiogenesis via the membrane G‐protein coupled estrogen receptor (GPER) and the key glycolytic protein PFKFB3 as a downstream effector. We herein investigated whether estrogenic agents regulate the stability and/or degradation of glycolytic

Anti‐sclerostin monoclonal antibody romosozumab, a treatment for osteoporosis, reduced vertebral fracture risk and clinical fracture. Laser irradiation triggers various effects, including bio‐stimulation, which can induce beneficial therapeutic effects and biological responses. Originally, we performed in vivo experiments to clarify the mechanism of better bone healing in laser‐ablated bone. Here,

The integrity of the genetic material is crucial for every organism. One intrinsic attack to genome stability is stalling of the replication fork which can result in DNA breakage. Several factors, such as DNA lesions or the formation of stable secondary structures (eg, G‐quadruplexes) can lead to replication fork stalling. G‐quadruplexes (G4s) are well‐characterized stable secondary DNA structures

Secretion of pulmonary surfactant in the alveoli of the lungs is essential to maintain lung function. Stretching of alveoli during lung inflation is the main trigger for surfactant secretion. Yet, the molecular mechanisms how mechanical distension of alveoli results in surfactant secretion are still elusive. The alveolar epithelium consists of alveolar epithelial type I (ATI) and surfactant secreting

Mechanical stimulations can prevent bone loss, but their effects on the tumor‐invaded bone or solid tumors are elusive. Here, we evaluated the effect of knee loading, dynamic loads applied to the knee, on metastasized bone and mammary tumors. In a mouse model, tumor cells were inoculated to the mammary fat pad or the proximal tibia. Daily knee loading was then applied and metabolic changes were monitored

Following mechanical loading, osteoblasts may arise via activation, differentiation, or proliferation to form bone. Our objective was to ablate proliferating osteoblast lineage cells in order to investigate the importance of these cells as a source for loading‐induced bone formation. We utilized 3.6Col1a1‐tk mice in which replicating osteoblast lineage cells can be ablated in an inducible manner using

Class Ia phosphoinositide 3‐kinases (PI3K) are critical mediators of insulin and growth factor action. We have demonstrated that the p85α regulatory subunit of PI3K modulates the unfolded protein response (UPR) by interacting with and regulating the nuclear translocation of XBP‐1s, a transcription factor essential for the UPR. We now show that PI3K activity is required for full activation of the UPR

Osteoclast‐mediated inflammatory bone resorption is a major cause of many inflammatory bone disorders, including rheumatoid arthritis and periodontitis. However, the mechanisms regulating osteoclast differentiation in inflammatory settings are not well understood. We demonstrate here that early estrogen‐induced gene 1 (EEIG1)‐deficient mice are protected from inflammatory bone loss as determined with

Staphylococcus aureus is the main cause of septic arthritis in humans, a disease associated with high morbidity and mortality. Inflammation triggered in response to infection is fundamental to control bacterial growth but may cause permanent tissue damage. Here, we evaluated the role of Lipoxin A4 (LXA4) in S aureus‐ induced arthritis in mice. Septic arthritis was induced by S aureus injection into

Lung cancer is one of most common malignancies worldwide. We have previously identified retinoic acid‐induced gene G (Rig‐G) as a tumor suppressor in not only acute promyelocytic leukemia, but also in other solid tumors. However, the clinical significance of Rig‐G and the underlying mechanism(s) for its biological function in lung cancer remain largely unexplored. Herein, we first compared the expression

Mice deficient in intestinal epithelial TLR9 develop small intestinal Paneth cell hyperplasia and higher Paneth cell IL‐17A levels. Since small intestinal Paneth cells and IL‐17A play critical roles in hepatic ischemia reperfusion (IR) injury, we tested whether mice lacking intestinal TLR9 have increased hepatic IR injury. Mice lacking intestinal TLR9 had profoundly increased liver injury after hepatic

Hematopoietic stem and progenitor cells (HSPCs) have the ability to self‐renew and differentiate into various blood cells, thus playing an important role in maintenance of lifelong hematopoiesis. Brahma‐related gene 1 (BRG1), which acts as the ATP subunit of mammalian SWI‐SNF‐related chromatin remodeling complexes, is involved in human acute myeloid leukemia and highly expresses in short‐term HSPCs

Equal segregation of chromosomes during mitosis ensures euploidy of daughter cells. Defects in this process may result in an imbalance in the chromosomal composition and cellular transformation. Proteolytic and non‐proteolytic ubiquitylation pathways ensure directionality and fidelity of mitotic progression but specific mitotic functions of deubiquitylating enzymes (DUBs) remain less studied. Here

Inhibitors of cAMP‐phosphodiesterase 4 (PDE4) exert a number of promising therapeutic benefits, but adverse effects, in particular emesis and nausea, have curbed their clinical utility. Here, we show that PAN‐selective inhibition of PDE4, but not inhibition of PDE3, causes a time‐ and dose‐dependent accumulation of chow in the stomachs of mice fed ad libitum without changing the animals' food intake

Targeted drug delivery to the endothelium has the potential to generate localized therapeutic effects at the blood‐tissue interface. For some therapeutic cargoes, it is essential to maintain contact with the bloodstream to exert protective effects. The pharmacokinetics (PK) of endothelial surface‐targeted affinity ligands and biotherapeutic cargo remain a largely unexplored area, despite obvious translational

Pathogenic mycobacteria, such as Mycobacterium tuberculosis, Mycobacterium bovis, and Mycobacterium marinum, can trigger NLRP3 inflammasome activation leading to maturation and secretion of interleukin 1β (IL‐1β). However, the mycobacterial factors involved in the activation of NLRP3 inflammasome are not fully understood. Here, we identified that the PPE family protein PPE13 was responsible for the

A relationship between COVID‐19 infection and an increasing incidence of atrial fibrillation has been observed. However, the underlying pathophysiology as a precipitant to AF has not been reviewed. This paper will consider the possible pathological and immunological AF mechanisms as a result, of COVID‐19 infection. We discuss the role myocardial microvascular pericytes expressing the ACE‐2 receptor

Drug delivery across the blood‐brain barrier (BBB) remains a significant obstacle for the development of neurological disease therapies. The low penetration of blood‐borne therapeutics into the brain can oftentimes be attributed to the restrictive nature of the brain microvascular endothelial cells (BMECs) that comprise the BBB. One strategy beginning to be successfully leveraged is the use of endogenous

Glucose is a major energy substrate for the fetus, including liver, heart, and brain metabolism. The umbilical vein (UV) blood flow supplies the fetal liver directly from the placenta, whereas a fraction is shunted via ductus venosus (DV) to the fetal systemic circulation bypassing the fetal liver. We hypothesized UV glucose concentration to be a major regulator of the distribution of glucose supply

Mineralocorticoid receptor antagonists (MRAs) are recommended for the treatment of heart failure and hypertension, mainly due to their natriuretic and anti‐fibrotic mode of action. Rodent studies have shown that MRAs can prevent adverse metabolic consequences of obesity but an elucidation of underlying molecular mechanisms is missing. Here, we investigated metabolic effects of the novel non‐steroidal

Increasing evidence indicates that circular RNAs (circRNAs) play a crucial role in regulating microRNAs (miRs) and mRNAs during breast cancer (BC) progression. Based on the in silico analysis of circRNA/miR/mRNA in BC, we aim to define an important role of circRNA_000554 in BC in relation to miR‐182 and zinc finger protein 36 (ZFP36). Low expression of circRNA_000554 and ZFP36, and high miR‐182 expression

α‐Synuclein (α‐syn)‐induced neurotoxicity has been generally accepted as a key step in the pathogenesis of Parkinson's disease (PD). Microtubule‐associated protein tau, which is considered second only to α‐syn, has been repeatedly linked with PD in association studies. However, the underlying interaction between these two PD‐related proteins in vivo remains unclear. To investigate how the expression

Lycium barbarum berry (gouqi , Goji, goji berry, or wolfberry), a traditional medicine and functional food, has a wide range of biological effects, including immuno‐modulation, anti‐aging, antitumor, neuro‐protection, and hepato‐protection. However, thus far, little is known about the traditional effects of L. barbarum on strengthening muscles. Therefore, this study focused on the effects of an extract

Currently, no treatment exists to improve semen quality in most infertile men. Here, we demonstrate systemic and direct effects of Fibroblast growth factor 23 (FGF23) and Klotho, which normally regulate vitamin D and mineral homeostasis, on testicular function. Direct effects are plausible because KLOTHO is expressed in both germ cells and spermatozoa and forms with FGFR1 a specific receptor for the

Obesity and related metabolic disorders are associated with intestinal microbiota dysbiosis, disrupted intestinal barrier, and chronic inflammation. Neohesperidin (Neo), a natural polyphenol abundant in citrus fruits, is known for its preventative and therapeutic effects on numerous diseases. Here, we report that Neo administration attenuates weight gain, low‐grade inflammation, and insulin resistance

Hypoxia is a key pathogenetic characteristic of chronic kidney disease (CKD). Klotho has renoprotective effect and its expression is commonly suppressed in CKD patients. We showed that chronic hypoxia in unilateral ureteral obstruction model mice is associated with renal Klotho promoter methylation and expression silencing. Administration of low‐dose of sodium hydrosulfide (NaHS) effectively ameliorated

Although it is known that zinc has several beneficial roles in the context of gut inflammation, the underlying mechanisms have not been extensively characterized. Zinc (Zn) is known to be the primary physiological inducer of the expression of the metallothionein (MT) superfamily of small stress‐responsive proteins. The expression of MTs in various tissues is induced or enhanced (including the gastrointestinal

Myristoylated alanine‐rich C‐kinase substrate (MARCKS) is an intracellular receptor for polysialic acid. MARCKS supports development, synaptic plasticity, and regeneration after injury. MARCKS binds with its functionally essential effector domain (ED) to polysialic acid. A 25‐mer peptide comprising the ED of MARCKS stimulates neuritogenesis of primary hippocampal neurons after addition to the culture

Thermosensitive transient receptor potential vanilloid 2 (thermoTRPV2) is a nonselective Ca2+‐permeable cation channel broadly expressed, and is implicated in the pathology of diseases such as diabetes and pancreatitis. However, the physiological and pharmacological functions of TRPV2 channels have not been extensively investigated because of the absence of specific modulators. In this study, we report

Circulating mitochondrial DNA (mtDNA), widely studied as a disease biomarker, comprises of mtDNA located within mitochondria, indicative of mitochondrial function, and cell‐free (cf) mtDNA linked to inflammation. The purpose of this study was to determine the ranges of, and relationship between, cellular and cf mtDNA in human blood. Whole blood from 23 controls (HC) and 20 patients with diabetes was

Although previous studies have shown that the administration of fibroblast growth factor 21 (FGF21) reverses hepatic steatosis, the mechanism by which FGF21 exerts a therapeutic effect on nonalcoholic fatty liver disease (NAFLD) is not yet entirely understood. We previously demonstrated that hepatic six transmembrane protein of prostate 2 (STAMP2) may represent a suitable target for NAFLD. We investigated

The retinal pigment epithelium (RPE) is a particularly vulnerable tissue to age‐dependent degeneration. Over the life span, the RPE develops an expanded endo‐lysosomal compartment to maintain the high efficiency of phagocytosis and degradation of photoreceptor outer segments (POS) necessary for photoreceptor survival. As the assembly and activation of the mechanistic target of rapamycin complex 1 (mTORC1)

Lipid mediators play important roles in regulating inflammatory responses and tissue homeostasis. Since 12/15‐lipoxygenase (12/15‐LOX)‐derived lipid mediators such as lipoxin A4 (LXA4) and protectin D1 (PD1) protect against corneal epithelial cell damage, the major cell types that express 12/15‐LOX and contribute to the corneal wound healing process are of particular interest. Here, we found that eosinophils

Genetic variation of insulin receptor substrate 1 (IRS‐1) was found to modulate the insulin resistance of adipose tissues, but the underlying mechanism was not clear. To investigate how the IRS‐1 was involved in the browning of white adipose tissue through miRNA, we identified a mutated Irs‐1 (Irs‐1−/− ) mice model and found that this mice had a reduced subcutaneous WAT (sWAT) and increased brown adipose

Brain zinc dysregulation is linked to many neurological disorders. However, the mechanisms regulating brain zinc homeostasis are poorly understood. We performed secondary analyses of brain MRI GWAS and exome sequencing data from adults in the UK Biobank. Coding ZIP12 polymorphisms in zinc transporter ZIP12 (SLC39A12) were associated with altered brain susceptibility weighted MRI (swMRI). Conditional

miR‐375‐3p is a significantly downregulated miRNA in bladder cancer (BC). However, its role in BC regulation is still unclear. In this study, we reported that miR‐375‐3p overexpression inhibited proliferation and migration and promoted apoptosis in BC cells. Frizzled‐8 (FZD8) gene is identified as the direct miR‐375‐3p targeting gene. miR‐375‐3p blocks the Wnt/β‐catenin pathway and downstream molecules

Ferrochelatase (FECH) is the terminal enzyme in heme biosynthesis. We previously showed that FECH is required for endothelial cell growth in vitro and choroidal neovascularization in vivo. But FECH has not been explored in retinal neovascularization, which underlies diseases like proliferative diabetic retinopathy and retinopathy of prematurity. Here, we investigated the inhibition of FECH using genetic

Meiosis initiation is a crucial step for the production of haploid gametes, which occurs from anterior to posterior in fetal ovaries. The asynchrony of the transition from mitosis to meiosis results in heterogeneity in the female germ cell populations, which limits the studies of meiosis initiation and progression at a higher resolution level. To dissect the process of meiosis initiation, we investigated

Although collagens are the most abundant proteins implicated in various disease pathways, essential mechanisms required for their proper folding and assembly are poorly understood. Heat‐shock protein 47 (HSP47), an ER‐resident chaperone, was mainly reported to fulfill key functions in folding and secretion of fibrillar collagens by stabilizing pro‐collagen triple‐helices. In this study, we demonstrate

MHC‐II on alveolar type‐II (AT‐II) cells is associated with immune tolerance in an inflammatory microenvironment. Recently, we found TNF‐α upregulated MHC‐II in AT‐II in vitro. In this study, we explored whether TNF‐α‐mediated inflammation upregulates MHC‐II on AT‐II cells to trigger Treg expansion in inflammation‐driven lung adenocarcinoma (IDLA). Using urethane‐induced mice IDLA model, we found that

Nicotinic acid adenine dinucleotide phosphate (NAADP) is the most potent Ca2+ mobilizing second messenger whose formation has remained elusive. In vitro, CD38‐mediated NAADP synthesis requires an acidic pH and a nonphysiological concentration of nicotinic acid (NA). We discovered that CD38 catalyzes synthesis of NAADP by exchanging the nicotinamide moiety of nicotinamide adenine dinucleotide phosphate

Hematopoietic gene delivery, such as hematopoietic stem/progenitor cells (HSPCs), is a promising treatment for both inherited and acquired diseases, such as hemophilia. Recently, a combined strategy to achieve more than 90% transduction efficiency was documented using recombinant adeno‐associated virus serotype 6 (rAAV6) vectors. However, the mechanisms of enhanced vector transduction efficiency in

Fibro/adipogenic progenitors (FAPs) are the main cellular source of fatty degeneration in muscle injury; however, the underlying mechanism of FAP adipogenesis in muscle degeneration needs to be further examined. Matrix metalloproteinase 14 (MMP‐14) has been reported to induce the adipogenesis of 3T3‐L1 preadipocytes, but whether MMP‐14 also regulates the differentiation of FAPs remains unclear. To

The proto‐oncogene ets1 is highly expressed in the pre‐migratory and migratory neural crest (NC), and has been implicated in the delamination and migration of the NC cells. To identify the downstream target genes of Ets1 in this process, we did RNA sequencing (RNA‐Seq) on wild‐type and ets1 mutant X. tropicalis embryos. A list of genes with significantly differential expression was obtained by analyzing

The androgen receptor (AR) is a major driver of prostate cancer (PCa) and a key therapeutic target for AR inhibitors (ie, Enzalutamide). However, Enzalutamide only inhibits androgen‐dependent AR signaling, enabling intrinsic AR activation via androgen‐independent pathways, leading to aggressive castration‐resistant PCa (CRPC). We investigated the ability of novel anti‐cancer agents, Dp44mT and DpC

Renal tubulointerstitial fibrosis (TIF) is a common pathological feature of aristolochic acid (AA) nephropathy (AAN). G2/M arrest of proximal tubular cells (PTCs) is implicated in renal fibrosis of AAN, but the upstream regulatory molecule remains unknown. Hypoxia inducible factor‐1α (HIF‐1α) promotes renal fibrosis in kidney disease, but the role of HIF‐1α in AAN is unclear. Evidence shows that HIF‐1α

The role of type II alveolar epithelial stem cells (AEC II) for alveolar repair in radiation‐induced lung fibrosis (RILF) remains largely unknown, mainly because of AEC II phenotype's spontaneous change in vitro. Cell differentiation status is determined by Lin28 and let‐7 miRNAs in see‐saw‐pattern. Lin28, a repressor of let‐7 and a stem cell marker, is activated by β‐catenin. The expression of β‐catenin

Akt, a crucial protein involved in a variety of signaling pathways in cancer, acts as an important regulator of survival in hepatocellular carcinoma (HCC), and provides curative option for the related drugs development. We have found an active phenanthroindolizidine alkaloid, (13aR ,14R )‐9,11,12,13,13a,14‐hexahydro‐3,6,7‐trimethoxydibenzo[f,h ]pyrrolo[1,2‐b ]isoquinolin‐14‐ol (HTBPI), is a promising

The clinically successful adjuvant MF59 is used in seasonal influenza vaccines, which is proposed to enhance immunity by creating an immune‐competent microenvironment in the muscle that allows recruitment of immune cells that drive adaptive immune responses. Here, we examined whether the clinically successful adjuvants MF59/AddaVax could be used for subcutaneous use and how antigen delivery can be

Given the rising evidence that gut malfunction including changes in the gut microbiota composition, plays a major role in the development of obesity and associated metabolic diseases, the exploring of novel probiotic bacteria with potential health benefits has attracted great attention. Recently Lactobacillus spp., exert potent anti‐obesity effects by regulating key transcriptional and translational

Small‐molecule inhibitors of abnormal protein self‐assembly are promising candidates for developing therapy against proteinopathies. Such compounds have been examined primarily as inhibitors of amyloid β‐protein (Aβ), whereas testing of inhibitors of other amyloidogenic proteins has lagged behind. An important issue with screening compound libraries is that although an inhibitor suitable for therapy

In the article, “Psoralen accelerates bone fracture healing by activating both osteoclasts and osteoblasts” by Tan Zhang, Weiqi Han, Kangxian Zhao, Wanlei Yang, Xuanyuan Lu, Yewei Jia, An Qin, and Yu Qian, in FASEB J. April 2019;33:5399‐5410 (doi: 10.1096/fj.201801797R), there is an error in Figure 5. FIGURE 5 Open in figure viewer Psoralen accelerates bone fracture healing via activation of osteoclasts

Type I interferons play a pivotal role in innate immune response to virus infection. The protein tyrosine phosphatase SHP‐1 was reported to function as a negative regulator of inflammatory cytokine production by inhibiting activation of NF‐κB and MAPKs during bacterial infection, however, the role of SHP‐1 in regulating type I interferons remains unknown. Here, we demonstrated that knockout or knockdown

Monocyte‐derived macrophages are the major innate immune cells that provide the first line of cellular defense against infections or injuries. These recruited macrophages at the site of inflammation are exposed to a broad range of cytokines that categorically incite a robust pro‐inflammatory response. However, macrophage pro‐inflammatory activation must be under exquisite control to avert unbridled