Over the past several decades, it has become increasingly clear that women have distinct cardiovascular profiles compared to men. In this review, our goal is to provide an overview of the literature regarding the influences of female sex and reproductive hormones (primarily estradiol) on mechanisms of cardiovascular control relevant to regulation of blood pressure, body temperature, and cerebral blood

Prevention of kidney fibrosis is an essential requisite for effective therapy in preventing chronic kidney disease (CKD). Here, we identify Old astrocyte specifically induced substance (OASIS)/cAMP responsive element‐binding protein 3‐like 1 (CREB3l1), a CREB/ATF family transcription factor, as a candidate profibrotic gene that drives the final common pathological step along the fibrotic pathway in

Correction for “Hepatic signaling by the mechanistic target of rapamycin complex 2 (mTORC2),” by Dudley W. Lamming, Gokhan Demirkan, Joan M. Boylan, Maria M. Mihaylova, Tao Peng Jonathan Ferreira, Nicola Neretti, Arthur Salomon, David M. Sabatini, and Philip A. Gruppuso, which was first published September 26, 2013; 10.1096/fj.13‐237743 (FASEB J. 28, 300–315). The authors note that there is an error

Correction for “TLR4‐MAP4K4 signaling pathway in models of oxygen‐induced retinopathy,” by Wenwen Chen, Juan Zhang, Peijun Zhang, Fangyuan Hu, Tingting Jiang, Junxiang Gu, and Qing Chang, which was first published in November 26, 2018; 10.1096/fj.201801086R (FASEB J. 33, 3451–3464). The authors note that there is a composition error in Figure 7. In the color keys for the bar graphs, the identifying

Disruption of extravillous trophoblast (EVT) migration and invasion is considered to be responsible for pathological placentation in preeclampsia (PE). Cyclin G2 (CCNG2) is an atypical cyclin that inhibits cell cycle progression. However, its biological function and underlying molecular mechanism in PE are poorly understood. In this study, clinical data demonstrated that CCNG2 was significantly upregulated

Skeletal muscles have a high metabolic capacity, which play key roles in glucose metabolism. Although periodontal disease increases the risk of metabolic syndrome, the relationship between periodontal bacterial infection and skeletal muscle metabolic dysfunction is unclear. We found that anti‐Porphyromonas gingivalis (Pg) antibody titers positively correlated with intramuscular adipose tissue content

Transfer across the blood‐brain barrier (BBB) remains a significant hurdle for the development of biopharmaceuticals with therapeutic effects within the central nervous system. We established a functional selection method to identify high affinity single domain antibodies to the transferrin receptor 1 (TfR1) with efficient biotherapeutic delivery across the BBB. A synthetic phage display library based

Neuropathic pain (NP) is a common complication that negatively affects the lives of patients with spinal cord injury (SCI). The disruption in the balance of excitatory and inhibitory neurons in the spinal cord dorsal horn contributes to the development of SCI and induces NP. The calcium‐binding protein (CaBP) calbindin‐D 28K (CaBP‐28K) is highly expressed in excitatory interneurons, and the CaBP parvalbumin

Fear memory is a pivotal biological function by which organisms can predict possible danger to avoid or reduce harm. However, dysregulation of fear memory processing may lead to pathological fear or anxiety and produce serious clinical symptoms, such as post‐traumatic stress disorder (PTSD). Iron deficiency (ID) is reported to inhibit the initiation of fear memory. In our study, we found that ferroportin1

Human adipose‐derived stem cells (hASCs) are ideal seed cells for tissue engineering due to their multidirectional differentiation potential. Microfilaments, microtubules, and intermediate filaments are responsible for supporting the intracellular space. Vimentin, a type III intermediate filament protein that is specifically expressed in cells of mesenchymal origin, can function as a scaffold and endow

Autophagy, a cellular stress response to starvation and bacterial infection, is executed by double‐membrane‐bound organelles called autophagosomes. Autophagosomes transfer cytosolic material to acidified lysosomes for degradation following soluble N‐ethylmaleimide‐sensitive factor attachment receptor (SNARE)‐dependent fusion processes. Many of the autophagy‐related disorders stem from defective end‐step

Consistent with increasing findings, extracellular vesicles (EVs), consider as a major constituents of the aqueous humor, have a role as signaling mediators in glaucoma. Following secretion, EVs hold immense promise for utilization as bio‐therapeutics and drug delivery vehicles due to their nature as biological nanoparticles that facilitate intercellular molecular transport. Yet, the specific pathway

Disassembly of tight junctions is a major cause of intestinal barrier dysfunction under total parenteral nutrition (TPN), but the precise mechanisms have not been fully understood. Normally, RNA binding protein Lin 28A is highly restricted to embryonic stem cells and dramatically decreases as differentiation progresses; however, in our preliminary study it was found aberrantly increased in the intestinal

In the midst of the current coronavirus pandemic, the United States continues to struggle with an ongoing opioid epidemic, initially fueled by widespread prescribing of opioid medications during the 1990s. The primary reason for prescribing opioids is to treat pain. Women have more acute and chronic pain and have been prescribed these drugs in significantly greater numbers than men. Comparison of women

To date, there are limited and incomplete data on possible sex‐based differences in fiber‐types of skeletal muscle and their response to physical exercise. Adult healthy male and female mice completed a single bout of endurance exercise to examine the sex‐based differences of the peroxisome proliferator‐activated receptor gamma coactivator 1 alpha (PGC1α), heat shock protein 60 (Hsp60), interleukin

The tumor suppressor p53 is known as a critical mediator of many cellular processes, including cellular senescence, but its role in mitochondrial dynamics is not fully understood. We have previously shown that p53 regulates mitochondrial dynamics via the PKA‐Drp1 pathway to induce cellular senescence. In this study, to further understand the role of p53‐dependent regulation of mitochondrial dynamics

Maintaining ovarian steroidogenesis is of critical importance, considering that steroid hormones are required for successful establishment and maintenance of pregnancy and proper development of embryos and fetuses. Investigating the mechanism that butyrate modulates the ovarian steroidogenesis is beneficial for understanding the impact of lipid nutrition on steroidogenesis. Herein, we identified that

Pregnancy complications associated with prenatal hypoxia lead to increased placental oxidative stress. Previous studies suggest that prenatal hypoxia can reduce mitochondrial respiratory capacity and mitochondrial fusion, which could lead to placental dysfunction and impaired fetal development. We developed a placenta‐targeted treatment strategy using a mitochondrial antioxidant, MitoQ, encapsulated

Study of vocal fold (VF) mucosal biology requires essential human vocal fold epithelial cell (hVFE) lines for use in appropriate model systems. We steadily transfected a retroviral construct containing human telomerase reverse transcriptase (hTERT) into primary normal hVFE to establish a continuously replicating hVFE cell line. Immortalized hVFE across passages have cobblestone morphology, express

Tumors of the nervous system including glioblastoma multiforme (GBM) are the most frequent and aggressive form of brain tumors; however, little is known about the impact of the circadian timing system on the formation, growth, and treatment of these tumors. We investigated day/night differences in tumor growth after injection of A530 glioma cells isolated from malignant peripheral nerve sheath tumor

Laminar shear stress generated by blood flow stimulates endothelial cells and activates signal transduction, which plays an important role in vascular homeostasis. Several lines of evidence indicate that membrane and intracellular lipids are involved in the signal transduction of biomechanical stresses. In this study, we performed global profiling of cellular lipids from human pulmonary artery endothelial

The noncoding RNAs play important role in growth and development of mammalian skeletal muscle. Recent work has shown that circRNAs are abundant in skeletal muscle tissue, with significant changes in their expression patterns during muscle development and aging. We identified a novel circRNA called circARID1A that is highly expressed in mice skeletal muscle compare to its linear transcript. Experiments

Lipocalin‐2 (LCN2) has been implicated in promoting apoptosis and neuroinflammation in neurological disorders; however, its role in neural transplantation remains unknown. In this study, we cultured and differentiated Lund human mesencephalic (LUHMES) cells into human dopaminergic‐like neurons and found that LCN2 mRNA was progressively induced in mouse brain after the intrastriatal transplantation

Cryptochromes are photoreceptors that mediate the circadian entrainment by light in plants and animals. They are also involved in magnetic field sensing in some animals. Recent studies suggest that cryptochromes play an essential role in metabolism and cardiovascular disease. However, the tissue‐specific function of cryptochromes in atherosclerosis is unknown. We transplanted bone marrow from wild‐type

Regulation of sphingolipid metabolism plays a role in cellular homeostasis, and dysregulation of these pathways is involved in cancer progression. Previously, our reports identified ceramide as an anti‐metastatic lipid. In the present study, we investigated the biochemical alterations in ceramide‐centered metabolism of sphingolipids that were associated with metastatic potential. We established metastasis‐prone

Mitochondrial derangement is an important contributor to the pathophysiology of muscular dystrophies and may be among the earliest cellular deficits. We have previously shown that disruption of Mss51, a mammalian skeletal muscle protein that localizes to the mitochondria, results in enhanced muscle oxygen consumption rate, increased endurance capacity, and improved limb muscle strength in mice with

Interleukin 33 (IL33) signaling has been implicated in the establishment and maintenance of pregnancy and in pregnancy disorders. The goal of this project was to evaluate the role of IL33 signaling in rat pregnancy. The rat possesses hemochorial placentation with deep intrauterine trophoblast invasion; features also characteristic of human placentation. We generated and characterized a germline mutant

Despite significant evidence that Rac1 is localized to the nucleus, little is known regarding the function and biological significance of nuclear Rac1. Here, we showed that in response to EGF Rac1 was translocated to nuclear speckles and co‐localized with the nuclear speckle marker Serine/arginine‐rich splicing factor 2 (SRSF2) in Cos‐7 cells. We also showed that the nuclear speckle localization of

Epilepsy is a common brain disorder, repeated seizures of epilepsy may lead to a series of brain pathological changes such as neuronal or glial damage. However, whether circular RNAs are involved in neuronal injury during epilepsy is not fully understood. Here, we screened circIgf1r in the status epilepticus model through circRNA sequencing, and found that it was upregulated after the status epilepticus

Multidrug resistance protein 4 (Mrp4) is an efflux transporter known to transport several xenobiotics and endogenous molecules. We recently identified that the lack of Mrp4 increases adipose tissue and body weights in mice. However, the role of Mrp4 in adipose tissue physiology are unknown. The current study aimed at characterizing these specific roles of Mrp4 using wild‐type (WT) and knockout (Mrp4−/−)

Neuroblasts have a clustered phenotype critical for their unidirectional migration, which in part is dependent on signaling from microvascular endothelial cells (EC) and pericytes (PC). Diffusible signals secreted by vascular cells have been demonstrated to increase survival, proliferation, and differentiation of subventricular zone resident neural stem cells (NSC); however, the signals that promote

Serine proteases are a large family of enzymes critical for multiple physiological processes, and proven diagnostic and therapeutic targets in several clinical indications. The high similarity of active sites among different serine proteases posts a challenge to reach high selectivity for inhibitors of serine proteases targeting at the active site. Here, we demonstrated that one particular surface

Aldosterone, the main mineralocorticoid hormone in humans, plays a pivotal role in the control of water and salt reabsorption via activation of the mineralocorticoid receptor (MR). Alterations in MR signaling pathway lead to renal dysfunction, including chronic kidney disease and renal fibrosis, that can be prevented or treated with mineralocorticoid receptor antagonists (MRAs). Here, we used RNA‐Sequencing

The hypothalamic‐pituitary‐adrenal (HPA) axis plays a principal role in stress response regulation and has been implicated in the etiology of stress‐related disorders. The HPA axis regulates the normal synthesis and release of glucocorticoids; dysregulation of the HPA axis causes abnormal responses to stress. FK506‐binding protein 5 (FKBP5), a co‐chaperone of heat shock protein 90 in the glucocorticoid

This playful title is not only to rhyme with my actual one but also to convey a look back as well as forward, as this marks the first month after completing my initial 5‐year term as Editor‐in‐Chief. I am buoyed (and “relieved”) to have been given the privilege to continue and thank FASEB for wanting me to do so. We are now publishing more than twice the volume of papers as when I took over (451 in

Signal transducers and transcriptional activation 1 (Stat1) is a member of the STATs family, and its role in various biological responses, including cell proliferation, differentiation, migration, apoptosis, and immune regulation has been extensively studied. We aimed to investigate its role in pathological cardiac hypertrophy, which is currently poorly understood. Experiments using H9C2 cardiomyocytes

Myosin 18Aα is a myosin 2‐like protein containing unique N‐ and C‐terminal protein interaction domains that co‐assembles with myosin 2. One protein known to bind to myosin 18Aα is β‐Pix, a guanine nucleotide exchange factor (GEF) for Rac1 and Cdc42 that has been shown to promote dendritic spine maturation by activating the assembly of actin and myosin filaments in spines. Here, we show that myosin

Necrotizing enterocolitis (NEC) is one of the most severe gastrointestinal diseases affecting premature infants. It has been shown that NEC is associated with disrupted intestinal barrier and dysregulated endoplasmic reticulum (ER)‐stress response. It has also been shown that stem cells derived from amniotic fluid (AFSC) rescued intestinal injury in experimental NEC. Herein, we hypothesized that the

β‐barrel outer membrane proteins (β‐OMPs) play critical roles in nutrition acquisition, protein import/export, and other fundamental biological processes. The assembly of β‐OMPs in Gram‐negative bacteria is mediated by the β‐barrel assembly machinery (BAM) complex, yet its precise mechanism remains elusive. Here, we report two structures of the BAM complex in detergents and in nanodisks, and two crystal

SARS‐CoV and SARS‐CoV‐2 encode four structural and accessory proteins (spike, envelope, membrane and nucleocapsid proteins) and two polyproteins (pp1a and pp1ab). The polyproteins are further cleaved by 3C‐like cysteine protease (3CLpro) and papain‐like protease (PLpro) into 16 nonstructural proteins (nsps). PLpro is released from nsp3 through autocleavage, and then it cleaves the sites between nsp1/2

Correction for “The study of isotopic enrichment of water in human plasma and erythrocyte,” by Yuan‐Hau Lin, Ying‐Chi Wang, Mai‐Szu Wu,Kuo‐Cheng Lu,Hsin‐Yi Lin, Hsien‐Shou Kuo,Geen‐Dong Chang, Chun‐Mao Lin, and Chiaolong Hsiao, which was first published August 10, 2020; https://doi.org/10.1096/fj.202000388RR (FASEB J.34, 13049–13062). The authors note that the affiliation listing for Yuan‐Hau Linand

The voltage‐gated potassium channel Kv3.4 is a crucial regulator of nociceptive signaling in the dorsal root ganglion (DRG) and the dorsal horn of the spinal cord. Moreover, Kv3.4 dysfunction has been linked to neuropathic pain. Although kinases and phosphatases can directly modulate Kv3.4 gating, the signaling mechanisms regulating the expression and stability of the Kv3.4 protein are generally unknown

Numerous studies have confirmed that prenatal or early postnatal exposure to pesticides can lead to functional deficits in the developing brain. This study aimed to investigate whether combined exposure to paraquat (PQ) and maneb (MB) during puberty could cause permanent toxic effects in the neural system of rats. In addition, the neuroprotective function of taurine (T) and its possible mechanism were

Autophagy is a highly conserved catabolic process activated by fasting and caloric restriction. FXR, a receptor for primary bile acids, reverses the activity of cAMP‐response element binding protein (CREB) on autophagy‐related genes (Atg)s and terminates autophagy in the fed state. GPBAR1, a receptor for secondary bile acids, exerts its genomic effects via cAMP‐CREB pathway. By genetic and pharmacological

Among the fascinating adaptations to limiting oxygen conditions (hypoxia) is the suppression of food intake and weight loss. In humans, this phenomenon is called high‐altitude anorexia and is observed in people suffering from acute mountain syndrome. The high‐altitude anorexia appears to be conserved in evolution and has been seen in species across the animal kingdom. However, the mechanism underlying

Stem cell‐derived exosomes are emerging as novel and clinically relevant cell‐free therapeutics for regenerative therapy. This work focused on investigating the stimulation of fibroblasts by exosomes derived from umbilical cord‐derived mesenchymal stem cells (ucMSC) in a defined serum‐free three‐dimensional (3D) culture. 3D culture of ucMSC was carried out in medium supplemented with KnockOut serum

Acute kidney injury (AKI) is a common clinical problem, and patients who survive AKI have a high risk of chronic kidney disease (CKD). The mechanism of CKD post‐AKI, characterized by progressive renal fibrosis, is still unclear. Maladaptive tubular epithelial cells (TECs) after AKI are considered a leading cause of renal fibrosis post‐AKI. TECs under maladaptive repair manifest characteristics of senescence

Etoposide‐induced 2.4 (EI24) exerts tumor suppressor activity through participating in cell apoptosis, autophagy, and inflammation. However, its role in renal diseases has not been elucidated. This study showed that the EI24 level decreased gradually in the kidneys of mice with unilateral ureteral obstruction (UUO) and in another fibrosis model induced by diabetic kidney disease. The overexpression

When cells with excess DNA, such as tetraploid cells, undergo cell division, it can contribute to cellular transformation via asymmetrical chromosome segregation‐generated genetic diversity. Cell cycle progression of tetraploid cells is suppressed by large tumor suppressor 2 (LATS2) kinase‐induced inhibitory phosphorylation of the transcriptional coactivator Yes‐associated protein (YAP). We recently

Obese individuals often show low growth hormone (GH) secretion, which leads to reduced lipid mobilization and further fat accumulation. Pharmacological approaches to increase GH levels in obese individuals by GH injection or GH‐releasing hormone receptor agonist showed promising effects on fat reduction. However, side effects on glucose metabolism and the heavy costs on making large peptides hindered

Preclinical studies have demonstrated that activation of the NOTCH pathway plays a key role in the pathogenesis of kidney damage. There is currently no information on the role of the Delta‐like homologue 1 (DLK1), a NOTCH inhibitor, in the regulation of renal damage. Here, we investigated the contribution of DLK1 to experimental renal damage and the underlying molecular mechanisms. Using a Dlk1‐null

The excretion and reabsorption of uric acid both to and from urine are tightly regulated by uric acid transporters. Metabolic syndrome conditions, such as obesity, hypercholesterolemia, and insulin resistance, are believed to regulate the expression of uric acid transporters and decrease the excretion of uric acid. However, the mechanisms driving cholesterol impacts on uric acid transporters have been

Food withdrawal is usually used for accurate feed metabolizable energy (ME) assessment in poultry, but its effects on intestinal structure and the absorption of nutrients are unclear. In this study, broilers were fed ad libitum (CT) or withdrew food for 12 (FH12), 24 (FH24), 36 (FH36), or 48 hours (FH48). We showed that food withdrawal increased the energy assimilation when compared with the CT. Food

Thrombospondin‐1 (TSP1) is involved in corneal wound healing caused by chemical injury. Herein, we examined the effects of TSP1 on hypoxia‐induced damages and wound‐healing activity in human corneal epithelial (HCE) cells. Exosomal protein expression was determined using liquid chromatography‐tandem mass spectrometry, and HCE cell migration and motility were examined through wound‐healing assay and

During the last decades intermediate filaments (IFs) have emerged as important regulators of cellular signaling events, ascribing IFs with functions beyond the structural support they provide. The organ and developmental stage‐specific expression of IFs regulate cell differentiation within developing or remodeling tissues. Lack of IFs causes perturbed stem cell differentiation in vasculature, intestine

Aberrant expression of long noncoding RNA (lncRNA) H19 and microRNA (miR)‐29b has been implicated in the complications of diabetes mellitus (DM). As a common and important complication of DM, diabetic foot ulcer (DFU) is characterized by high incidence and poor prognosis. Herein, we explored the role of lncRNA H19 in wound healing of DFU. Differentially expressed DM‐related lncRNAs were initially screened

The protein tyrosine phosphatase SHP2, encoded by PTPN11, is ubiquitously expressed and essential for the development and/or maintenance of multiple tissues and organs. SHP2 is involved in gastrointestinal (GI) epithelium development and homeostasis, but the underlying mechanisms remain elusive. While studying SHP2’s role in skeletal development, we made osteoblast‐specific SHP2 deficient mice using

Chronic vascular inflammation plays a key role in the pathogenesis of atherosclerosis. Long non‐coding RNAs (lncRNAs) have emerged as essential inflammation regulators. We identify a novel lncRNA termed lncRNA‐MAP3K4 that is enriched in the vessel wall and regulates vascular inflammation. In the aortic intima, lncRNA‐MAP3K4 expression was reduced by 50% during the progression of atherosclerosis (chronic

Appropriate migration of cytotoxic T effector cells into the tumors is crucial for their antitumor function. Despite the controversial role of PI3K‐Akt in CD8+ T cell mTORC1 activation, a link between Akt‐mTORC1 signaling and CD8+ trafficking has been demonstrated. We have recently discovered that TCR‐induced calcineurin activates DAPK1, which interacts with TSC2 via its death domain and phosphorylates