The benefits of increased human lifespan depend upon duration of healthy, independent living; the healthspan. Bone-wasting disorders contribute significantly to loss of independence, frailty, and morbidity in older people. Therefore, there is an unmet need globally for lifestyle interventions to reduce the likelihood of bone fractures with age. Although many mechanisms are involved in disorders of

This study investigated the effect of apela on renal function and anti-inflammatory effect on whole body and kidney tissue in mice with type I cardiorenal syndrome (CRS). The murine type I CRS model was established and apela was subcutaneously infused for two weeks. Cardiac and renal functions were evaluated by echocardiography and blood biochemistry, respectively. The systemic and renal inflammatory

Exosomes are a novel class of intercellular signal modulators that contain a wide range of molecules and deliver information between cells and tissues. MicroRNAs (miRNAs), a type of regulatory non-coding RNA, are often incorporated into exosomes as signaling molecules. In this review, we discuss the expression of exosomal miRNAs from diverse origins such as tumor cells, solid tumor tissue, and biological

Postoperative pain and delayed healing in surgical wounds, which require complex management strategies have understudied complicated mechanisms. Here we investigated temporal changes in behavior, tissue structure, and transcriptomic profiles in a rat model of a surgical incision, using hyperalgesic behavioral tests, histological analyses, and next-generation RNA sequencing, respectively. The most rapidly

Obesity alters skeletal muscle lipidome and promotes myopathy, but it is unknown whether aberrant muscle lipidome contributes to the reduction in skeletal muscle contractile force-generating capacity. Comprehensive lipidomic analyses of mouse skeletal muscle revealed a very strong positive correlation between the abundance of lysophosphatidylcholine (lyso-PC), a class of lipids that is known to be

During development, erythroid cells are generated by two waves of hematopoiesis. In zebrafish, primitive erythropoiesis takes place in the intermediate cell mass region, and definitive erythropoiesis arises from the aorta-gonad mesonephros. TALE-homeoproteins Meis1 and Pbx1 function upstream of GATA1 to specify the erythroid lineage. Embryos lacking Meis1 or Pbx1 have weak gata1 expression and fail

Glioblastoma (GBM) is a refractory disease that has a highly infiltrative characteristic. Over the past decade, GBM perivascular niche (PVN) has been described as a route of dissemination. Here, we investigated that trailed membrane structures, namely retraction fibers (RFs), are formed by perivascular extracellular matrix (ECM) proteins. By using the anatomical GBM database, we validated that the

Many pandemic issues have been swirling around in our country, and most have received extensive media coverage, most notably vaccine hesitancy/resistance, the Delta variant, and the continuing extreme importance of masking. Another is the collective angst over the time it is taking the FDA to issue full approvals of the earliest vaccines to apply for it. (It is anticipated that at least one vaccine

Autosomal dominant polycystic kidney disease (ADPKD), caused by mutations of PKD1 or PKD2 genes, is characterized by development and growth of cysts causing progressive kidney enlargement. Reduced resting cytosolic calcium and increased cAMP levels associated with the tonic action of vasopressin are two central biochemical defects in ADPKD. Here we show that co-targeting two GPCRs, the vasopressin

Autosomal dominant polycystic kidney disease is a common inherited renal disorder that results from mutations in either PKD1 or PKD2, encoding polycystin-1 (PC1) and polycystin-2 (PC2), respectively. Downregulation or overexpression of PKD1 or PKD2 in mouse models results in renal cyst formation, suggesting that the quantity of PC1 and PC2 needs to be maintained within a tight functional window to

Satellite cells support adult skeletal muscle fiber adaptations to loading in numerous ways. The fusion of satellite cells, driven by cell-autonomous and/or extrinsic factors, contributes new myonuclei to muscle fibers, associates with load-induced hypertrophy, and may support focal membrane damage repair and long-term myonuclear transcriptional output. Recent studies have also revealed that satellite

Cadherin EGF LAG seven-pass G-type receptor 2 (CELSR2), a mammalian orthologue of drosophila flamingo, belongs to the cadherin subfamily. CELSR2 mainly function in neural development and cilium polarity. Recent studies showed that the CELSR2 gene is related to many human diseases, including coronary artery disease, idiopathic scoliosis, and cancer. Genome-Wide Association Studies data showed that SNP

In a recently published phase III clinical trial, gemcitabine (GEM) plus cisplatin (DDP) induction chemotherapy significantly improved recurrence-free survival and overall survival and became the standard of care among patients with locoregionally advanced NPC. However, the molecular mechanisms of GEM synergized with DPP in NPC cells remain elucidated. These findings prompt us to explore the effect

Group IIA secreted phospholipase A2 (PLA2G2A) hydrolyzes glycerophospholipids at the sn-2 position resulting in the release of fatty acids and lysophospholipids. C57BL/6 mice do not express Pla2g2a due to a frameshift mutation (wild-type [WT] mice). We previously reported that transgenic expression of human PLA2G2A in C57BL/6 mice (IIA+ mice) protects against weight gain and insulin resistance, in

The contribution of circulatory tau and β-amyloid in Parkinson's disease (PD), especially the cognitive function, remains inconclusive. Extracellular vesicles (EVs) cargo these proteins throughout the bloodstream after they are directly secreted from many cells, including neurons. The present study aims to investigate the role of the plasma EV-borne tau and β-amyloid as biomarkers for cognitive dysfunction

Endogenous tryptophan metabolism pathways lead to the production of serotonin (5-hydroxytryptamine; 5-HT), kynurenine, and several downstream metabolites which are involved in a multitude of immunological functions in both health and disease states. Ingested tryptophan is largely shunted to the kynurenine pathway (95%) while only minor portions (1%–2%) are sequestered for 5-HT production. Though often

Recent investigations of gut microbiota have contributed to understanding of the critical role of microbial community in pathophysiology. Dysbiosis not only causes disturbance directly to the gastrointestinal tract but also affects the liver through gut-liver axis. Various types of dysbiosis have been documented in alcoholic liver disease (ALD), nonalcoholic fatty liver disease, autoimmune hepatitis

Macrophages are a critical driver of neovessel formation in tissue-engineered vascular grafts (TEVGs), but also contribute to graft stenosis, a leading clinical trial complication. Macrophage depletion via liposomal delivery of clodronate, a first-generation bisphosphonate, mitigates stenosis, but simultaneously leads to a complete lack of tissue development in TEVGs. This result and the associated

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the development of bilateral renal cysts which enlarge continuously, leading to compression of adjacent intact nephrons. The growing cysts lead to a progressive decline in renal function. Cyst growth is driven by enhanced cell proliferation and chloride secretion into the cyst lumen. Chloride secretion is believed to occur mainly

The cardiac circadian clock is responsible for the modulation of different myocardial processes, and its dysregulation has been linked to disease development. How this clock machinery is regulated in the heart remains an open question. Because noradrenaline (NE) can act as a zeitgeber in cardiomyocytes, we tested the hypothesis that adrenergic signaling resets cardiac clock gene expression in vivo

The arterial wall consists of three concentric layers: intima, media, and adventitia. Beyond their resident cells, these layers are characterized by an extracellular matrix (ECM), which provides both biochemical and mechanical support. Elastin, the major component of arterial ECM, is present in the medial layer and organized in concentric elastic lamellae that confer resilience to the wall. We explored

Robust inflammatory responses are critical to survival following respiratory infection, with current attention focused on the clinical consequences of the Coronavirus pandemic. Epigenetic factors are increasingly recognized as important determinants of immune responses, and EZH2 is a prominent target due to the availability of highly specific and efficacious antagonists. However, very little is known

The leucine-rich repeat-containing family 8 member A (LRRC8A) is an essential subunit of the volume-regulated anion channel (VRAC). VRAC is critical for cell volume control, but its broader physiological functions remain under investigation. Recent studies in the field indicate that Lrrc8a disruption in the brain astrocytes reduces neuronal excitability, impairs synaptic plasticity and memory, and

Cardiovascular disease is the most prevalent cause of morbidity and mortality in diabetes. Epicardial adipose tissue (EAT) lies in direct contact with the myocardium and coronary arteries and can influence cardiac (patho) physiology through paracrine signaling pathways. This study hypothesized that the proteins released from EAT represent a critical molecular link between the diabetic state and coronary

Neuromyelitis optica (NMO) is an autoimmune disease that primarily targets astrocytes. Autoantibodies (NMO-IgG) against the water channel protein, aquaporin 4 (AQP4), are a serologic marker in NMO patients, and they are known to be responsible for the pathophysiology of the disease. In the brain, AQP4 is mainly expressed in astrocytes, especially at the end-feet, where they form the blood-brain barrier

The primary aims of this study were to determine the effects of lifelong exercise and detraining on age-related alterations in mitochondrial function, inflammation associated with senescence-associated secretory phenotype (SASP), and lipolysis in the perirenal fat and liver of rats. Female Sprague–Dawley rats were randomly assigned to four groups: young control (n = 12), old control (n = 12), detraining

In cattle, several calves born after IVP (“in vitro” embryo production) present similar birthweight to those generated after MOET (multiple ovulation and embryo transfer). However, the underlying molecular patterns in organs involved in the developmental process are unknown and could indicate physiological programming. The objectives of this study were: (1) to compare epigenomic and transcriptomic

Circulating neutrophil extracellular traps (NETs) resistant to t-PA have not been studied completely although NETs in thrombi may contribute to tissue plasminogen activator (t-PA) resistance. This research intended to elucidate whether circulating NETs are associated with t-PA resistance and the underlying mechanism. The levels of NETs were detected in the circulating neutrophils, ischemic brain tissue

Repeated implantation failure (RIF) is a major problem that limits the pregnancy rate associated with assisted reproductive technology. However, the pathogenesis of RIF is still unknown. Recently, the expression levels of circular RNAs (circRNAs) were profiled in the endometrial tissues of patients with RIF. However, the exact role of circRNAs in RIF remains unclear. In our study, we found that circFAM120A

Brown adipose tissue (BAT) plays an important role on no shivering thermogenesis during cold exposure to maintain animal body temperature and energy homeostasis. However, knowledge of the cellular transition from white adipose tissue (WAT) to BAT is still limited. In this study, we provided a comprehensive metabolomics and transcriptional signatures of goat BAT and WAT. A total of 157 metabolites were

Although commonly thought to produce prostacyclin (prostaglandin I2; PGI2) that evokes vasodilatation and protects vessels from the development of diseases, the endothelial cyclooxygenase (COX)-mediated metabolism has also been found to release substance(s) called endothelium-derived contracting factor(s) (EDCF) that causes endothelium-dependent contraction and implicates in endothelial dysfunction

In vertebrates, retinal rod and cone photoreceptor cells rely significantly on glycolysis. Lactate released from photoreceptor cells fuels neighboring retinal pigment epithelium cells and Müller glial cells through oxidative phosphorylation. To understand this highly heterogeneous metabolic environment around photoreceptor cells, single-cell analysis is needed. Here, we visualized cellular AMP-activated

Compared with the well-described XY sex determination system in mammals, the avian ZW sex determination system is poorly understood. Knockdown and overexpression studies identified doublesex and mab-3-related transcription factor 1 (DMRT1) as the testis-determining gene in chicken. However, the detailed effects of DMRT1 gene disruption from embryonic to adult development are not clear. Herein, we have

Correction for “Estrogen-related receptor α is involved in angiogenesis and skeletal muscle revascularization in hindlimb ischemia,” by Danesh H. Sopariwala, Neah Likhite, Guangsheng Pei, Fnu Haroon, Lisa Lin, Vikas Yadav, Zhongming Zhao, and Vihang A. Narkar, which was first published March 31, 2021; https://doi.org/10.1096/fj.202001794RR (FASEB J. 35, e21480). The authors report that G. Pei’s name

Correction for “Cf- 02, a novel benzamide-linked small molecule, blunts NF-κB activation and NLRP3 inflammasome assembly and improves acute onset of accelerated and severe lupus nephritis in mice,” by Shin-Ruen Yang Kuo-Feng Hua, Chih-Yu Yang, Ann Chen, Jui-Chun Weng, Yu-Ling Tsai, Chih-Jun Wan, Chung-Yao Wu, Chia-Chung Lee, Jia-Feng Chan, Chih-Yu Hsieh, Yu-Juei Hsu, Chia-Chao Wu, Debabrata Mukhopadhyay

COVID-19 is often characterized by dysregulated inflammatory and immune responses. It has been shown that the Traditional Chinese Medicine formulation Qing-Fei-Pai-Du decoction (QFPDD) is effective in the treatment of the disease, especially for patients in the early stage. Our network pharmacology analyses indicated that many inflammation and immune-related molecules were the targets of the active

Emerging research has highlighted the capacity of microRNA-23a-3p (miR-23a-3p) to alleviate inflammatory pain. However, the molecular mechanism by which miR-23a-3p attenuates inflammatory pain is yet to be fully understood. Hence, the current study aimed to elucidate the mechanism by which miR-23a-3p influences inflammatory pain. Bioinformatics was initially performed to predict the inflammatory pain

Success of adoptive cell therapy mainly depends on the ability of immune cells to persist and function optimally in the immunosuppressive tumor microenvironment. Although present at the cancer site, immune cells become exhausted and/or inhibited, due to the presence of inhibitory receptors such as PD-L1 on malignant cells. Novel genetic strategies to manipulate the PD1/PD-L1 axis comprise (i) PD-1

With an aging world population, there is an increased risk of fracture and impaired healing. One contributing factor may be aging-associated decreases in vascular function; thus, enhancing angiogenesis could improve fracture healing. Both bone morphogenetic protein 2 (BMP-2) and thrombopoietin (TPO) have pro-angiogenic effects. The aim of this study was to investigate the effects of treatment with

Hypoxia increases fetal hepatic insulin-like growth factor binding protein-1 (IGFBP-1) phosphorylation mediated by mechanistic target of rapamycin (mTOR) inhibition. Whether maternal nutrient restriction (MNR) causes fetal hypoxia remains unclear. We used fetal liver from a baboon (Papio sp.) model of intrauterine growth restriction due to MNR (70% global diet of Control) and liver hepatocellular carcinoma

Resistance training (RT) dynamically alters the skeletal muscle nuclear DNA methylome. However, no study has examined if RT affects the mitochondrial DNA (mtDNA) methylome. Herein, ten older, Caucasian untrained males (65 ± 7 y.o.) performed six weeks of full-body RT (twice weekly). Body composition and knee extensor torque were assessed prior to and 72 h following the last RT session. Vastus lateralis

Retinopathy of prematurity (ROP) remains one of the major causes of blindness in children worldwide. While current ROP treatments are mostly disruptive to reduce proliferative neovascularization by targeting the hypoxic phase, protection against early hyperoxia-induced retinal vascular loss represents an effective therapeutic window, but no such therapeutic strategy is available. Built upon our recent

Cyclic nucleotide-gated (CNG) channels are important mediators in the transduction pathways of rod and cone photoreceptors. Native CNG channels are heterotetramers composed of homologous A and B subunits. Biallelic mutations in CNGA1 or CNGB1 genes result in autosomal recessive retinitis pigmentosa (RP). To investigate the pathogenic mechanism of CNG channel-associated retinal degeneration, we developed

We highlight the ability of the tuberculosis (TB) causing bacterial pathogen, Mycobacterium tuberculosis (Mtb), to induce key characteristics that are associated with established IARC classified Group 1 and Group 2A carcinogenic agents. There is sufficient evidence from epidemiological case-control, cohort and meta-analysis studies of increased lung cancer (LC) risk in pre-existing/active/old TB cases

Blastocysts hatch from the zona pellucida (ZP) to enable implantation into the uterine endometrial epithelium, but little is known regarding the effect of hatching sites on pregnancy outcomes. Murine hatching embryos were categorized into five groups based on initial trophectoderm projection (TEP)/ZP position corresponding to the inner cell mass center. In blastocysts (3.5 dpc) post-12 hours in vitro

Desminopathy is the most common intermediate filament disease in humans. The most frequent mutation causing desminopathy in patients is a R350P DES missense mutation. We have developed a rat model with an analogous mutation in R349P Des. To investigate the role of R349P Des in mechanical loading, we stimulated the sciatic nerve of wild-type littermates (WT) (n = 6) and animals carrying the mutation

Duchenne muscular dystrophy (DMD) is an intractable genetic disease associated with progressive skeletal muscle weakness and degeneration. Recently, it was reported that intraperitoneal injections of ketone bodies partially ameliorated muscular dystrophy by increasing satellite cell (SC) proliferation. Here, we evaluated whether a ketogenic diet (KD) with medium-chain triglycerides (MCT-KD) could alter

Loss of muscle mass and strength after disuse followed by impaired muscle recovery commonly occurs with aging. Metformin (MET) and leucine (LEU) individually have shown positive effects in skeletal muscle during atrophy conditions but have not been evaluated in combination nor tested as a remedy to enhance muscle recovery following disuse atrophy in aging. The purpose of this study was to determine

Biological functions, including glycemic control and bone metabolism, are highly influenced by the body's internal clock. Circadian rhythms are biological rhythms that run with a period close to 24 hours and receive input from environmental stimuli, such as the light/dark cycle. We investigated the effects of circadian rhythm disruption (CRD), through alteration of the light/dark schedule, on glycemic

Macrophage migration inhibitory factor (MIF), an immunoregulatory cytokine plays an important role in inflammation and the immune response, and has been described as having a potential role in immune evasion by parasites. Thelazia callipaeda, a vector-borne zoonotic eye worm with a broad host range, has been documented as an agent of ocular infection of thelaziosis. The ability of T. callipaeda to

Organic anion-transporting polypeptides, OATP1B1, OATP1B3, and OATP2B1 are multispecific membrane proteins mediating the hepatocellular uptake of structurally diverse endo- and exogenous compounds, including various kinds of drugs. Co-administration of OATP1B/2B1 substrates may lead to altered pharmacokinetics or even toxicity. Therefore, the study of the interaction with these OATPs is essential in

Skeletal muscle contains multiple cell types that work together to maintain tissue homeostasis. Among these, satellite cells (SC) and fibroadipogenic progenitors cells (FAPs) are the two main stem cell pools. Studies of these cells using animal models have shown the importance of interactions between these cells in repair of healthy muscle, and degeneration of dystrophic muscle. Due to the unavailability

Long noncoding RNAs (lncRNAs) are central regulators of the inflammatory response and play an important role in inflammatory diseases. PINT has been reported to be involved in embryonic development and tumorigenesis. However, the potential functions of PINT in the innate immune system are largely unknown. Here, we revealed the transcriptional regulation of inflammatory genes by PINT, whose expression

Memorizing pheromonal locations is critical for many mammalian species as it involves finding mates and avoiding competitors. In rodents, pheromonal information is perceived by the main and accessory olfactory systems. However, the role of somatosensation in context-dependent learning and memorizing of pheromone locations remains unexplored. We addressed this problem by training female mice on a multimodal

Myopia (short-sightedness), usually caused by excessive elongation of the eye during development, has reached epidemic proportions worldwide. In animal systems including the chicken model, several treatments have been shown to inhibit ocular elongation and experimental myopia. Although diverse in their apparent mechanism of action, each one leads to a reduction in the rate of ocular growth. We hypothesize

Mounting evidence demonstrates that paternal diet programs offspring metabolism. However, the contribution of a pre-conception paternal high protein (HP) diet to offspring metabolism, gut microbiota, and epigenetic changes remains unclear. Here we show that paternal HP intake in Sprague Dawley rats programs protective metabolic outcomes in offspring. Compared to paternal high fat/sucrose (HF/S), HP

Two distinct genetic mutational pathways characterized by either chromosomal instability or high-frequency microsatellite instability (MSI-H) are recognized in the pathogenesis of colorectal cancer (CRC). Recently, it has been shown that patients with primary CRC that displays MSI-H have a significant, stage-independent, multivariate survival advantage. Biological properties of CMS1 (MSI-H type) can

Withdrawal from contact inhibition is necessary for epithelial cancer precursor cells to initiate cell growth and motility. Nevertheless, little is understood about the mechanism for the sudden initiation of cell growth under static conditions. We focused on cellular junctions as one region where breaking out of contact inhibition occurs. In well-differentiated endometrial cancer cells, Sawano, the

Mycobacterium bovis is the causative agent of bovine tuberculosis and also responsible for serious threat to public health. Koumiss is a fermented mare's milk product, used as traditional drink. Here, we explored the effect of koumiss on gut microbiota and the host immune response against M bovis infection. Therefore, mice were treated with koumiss and fresh mare milk for 14 days before M bovis infection