Clinical Science (1979-)

Reductions in Na+-K+-ATPase (NKA) activity and expression are often observed in the progress of various reason-induced heart failure (HF). However, NKA α1 mutation or knockdown cannot cause spontaneous heart disease. Whether the abnormal NKAα1 directly contributes to HF pathogenesis remains unknown. Here, we challenge NKA α1 +/- mice with isoproterenol to evaluate the role of NKA α1 haploinsufficiency in isoproterenol (ISO)-induced cardiac dysfunction. Genetic knockdown of NKAα1 accelerated ISO-induced cardiac cell hypertrophy, heart fibrosis, and dysfunction...

Angiotensin Receptor blockers (ARBs) are the first-line treatment for hypertension; they act by inhibiting signaling through the angiotensin 1 receptor (AT1R). Recently, a novel biased AT1R agonist, TRV120027 (TRV), that selectively activates the β-arrestin cascade and blocks the G-protein-coupled receptor pathway has been proposed as a potential blood pressure medication. Here, we explored the effects of TRV and associated β-arrestin signaling in podocytes, essential cells of the kidney filter...

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder that is characterized by B and T lymphocyte dysfunction and altered cytokine production, including elevated levels of the adipocytokine leptin.  Leptin has various immunomodulatory properties, including promoting the expansion of proinflammatory Tlymphocytes and the proliferation and survival of B cells. In the present study, we hypothesized that leptin antagonism would improve B and T cell dysfunction and attenuate hypertension in an experimental model of SLE, the NZBWF1 mouse...

Sepsis is known to cause damage to the intestinal mucosa, leading to bacterial translocation, and exacerbation of both local and remote organ impairments. In this study, fecal samples were collected from both septic and healthy individuals. Analysis through 16s rRNA sequencing of the fecal microbiota revealed that sepsis disrupts the balance of the gut microbial community. Recent research has highlighted the association of lipid metabolism with disease. By analyzing the fecal metabolome, four lipid metabolites that showed significant differences between the two groups were identified: PE(O-16:0/0:0), PE(17:0/0:0), PE(0:0/14:0), and PE(12:0/20:5(5Z, 8Z, 11Z, 14Z, 17Z))...

Cyp2c70-deficient mice have a human-like bile acid (BA) composition due to their inability to convert chenodeoxycholic acid (CDCA) into rodent-specific muricholic acids (MCAs). However, the hydrophobic BA composition in these animals is associated with liver pathology. Although Cyp2c70-ablation has been shown to alter gut microbiome composition, the impact of gut bacteria on liver pathology in Cyp2c70-/- mice remains to be established. Therefore, we treated young-adult male and female wild-type (WT) and Cyp2c70-/- mice with antibiotics (AB) with broad specificity to deplete the gut microbiota and assessed the consequences on BA metabolism and liver pathology...

The inflammatory response and subsequent ventricular remodeling are key factors contributing to ventricular arrhythmias (VAs) after myocardial infarction (MI). Ubiquitin-specific protease 38 (USP38) is a member of the USP family, but the impact of USP38 in arrhythmia substrate generation after MI remains unclear. This study aimed to determine the role of USP38 in post-MI VAs and its underlying mechanisms.  Methods and Results: Surgical left descending coronary artery ligation was used to construct MI models...

The System L amino acid transporter, particularly the isoform Large Neutral Amino Acid Transporter Small Subunit 1 (LAT1) encoded by SLC7A5, is believed to mediate the transfer of essential amino acids in the human placenta. Placental System L amino acid transporter expression and activity is decreased in pregnancies complicated by IUGR and increased in fetal overgrowth. However, it remains unknown if changes in the expression of LAT1 are mechanistically linked to System L amino acid transport activity...

Dietary fructose is widely used in beverages, processed foods, and Western diets as food additives, and is closely related to the increased prevalence of multiple diseases, including inflammatory bowel disease (IBD). However, the detailed mechanism by which high fructose disrupts intestinal homeostasis remains elusive. This study showed that high fructose corn syrup (HFCS) administration exacerbated intestinal inflammation and deteriorated barrier integrity. Several in vivo experimental models were utilized to verify the importance of gut microbiota and immune cells in HFCS-mediated dextran sulfate sodium (DSS)-induced colitis...

The process of ovarian cryopreservation and transplantation is the only feasible fertility preservation method for prepubertal girls and female patients with cancer who cannot delay radiotherapy and chemotherapy. However, basic research on this technique is lacking. To better understand ovarian function and oocyte quality after ovarian tissue (OT) transplantation, we characterised the appearance, angiogenesis, and endocrine function of ovarian grafts in a murine model; the mitochondrial function and DNA damage in oocytes isolated from the OT; and the development of embryos after in vitro fertilisation...

Dialysis and kidney transplantation (Ktx) mitigate some of the physiological deficits in chronic kidney disease (CKD), but it remains to be determined if these mitigate microbial dysbiosis and the production of inflammatory microbial metabolites, which contribute significantly to the uraemic phenotype. We have investigated bacterial DNA signatures present in the circulation of CKD patients and those receiving a KTx. Our data are consistent with increasing dysbiosis as CKD progresses, with an accompanying increase in trimethylamine (TMA) producing pathobionts Pseudomonas and Bacillus...

Abdominal aortic aneurysm (AAA) is characterized by at least 1.5-fold enlargement of the infrarenal aorta, a ruptured AAA is life-threatening. Colchicine is a medicine used to treat gout and familial Mediterranean fever, and recently it was approved to reduce the risk of cardiovascular events in adult patients with established atherosclerotic disease. With an AAA mice model created by treatment with porcine pancreatic elastase (PPE) and beta aminopropionitrile (BAPN), this work was designed to explore whether colchicine could protect against the development of AAA...

Myeloid cells, including macrophages, play important roles as first responders to cardiac injury and stress.  Epidermal growth factor receptor (EGFR) has been identified as a mediator of macrophage responsiveness to select diseases, though its impact on cardiac function or remodeling following acute ischemic injury is unknown. We aimed to define the role of myeloid cell-specific EGFR in the regulation of cardiac function and remodeling following acute myocardial infarction (MI)-induced injury.  Floxed EGFR mice were bred with homozygous LysM-Cre (LMC) transgenic mice to yield myeloid-specific EGFR knockout (mKO) mice...

Airway-associated adipose tissue increases with body mass index and is a local source of pro-inflammatory adipokines that may contribute to airway pathology in asthma co-existing with obesity. Genetic susceptibility to airway adiposity was considered in the present study through kisspeptin/kisspeptin receptor signalling, known to modulate systemic adiposity and potentially drive airway remodelling. Therefore, the aim of the study was to determine the effects of kisspeptin/kisspeptin receptor signalling in the lung, focusing on airway-associated adipose tissue deposition and impact on airway structure-function...

BACKGROUND: Sepsis engenders an imbalance in the body's inflammatory response, with cytokines assuming a pivotal role in its progression. A relatively recent addition to the interleukin-17 family, denominated Interleukin-17D (IL-17D), is notably abundant within pulmonary confines. Nevertheless, its implication in sepsis remains somewhat enigmatic. This study endeavors to scrutinize the participation of IL-17D in sepsis-induced acute lung injury (ALI)...

Renal ischemia-reperfusion injuries (IRIs) are one of the leading causes of acute kidney injuries (AKIs). Selenium, as an essential trace element, is able to antioxidant stress and reduces inflammatory responses. The regulation mechanism of selenomethionine, one of the major forms of selenium intake by humans, is not yet clear in renal IRIs. Therefore, we aimed to explore the key targets and related mechanisms of selenomethionine regulation in renal IRIs and provide new ideas for the treatment of selenomethionine with renal IRIs...

Skeletal mandibular hypoplasia (SMH) is one of the most common skeletal craniofacial deformities in orthodontics, which was often accompanied by impaired chondrogenesis and increasing apoptosis of condylar chondrocytes. Therefore, protecting chondrocytes from apoptosis and promoting chondrogenesis in condylar growth is vital for treatment of SMH patients. Transferrin (TF) was highly expressed in condylar cartilage of newborn mice and was gradually declined as the condyle ceased growing. Interestingly, serum level of TF in SMH patients was significantly lower than normal subjects...

No abstract text is available yet for this article.

Ageing is a complex biological process associated with increased morbidity and mortality. Nine classic, interdependent hallmarks of ageing have been proposed involving genetic and biochemical pathways that collectively influence ageing trajectories and susceptibility to pathology in humans. Ageing skeletal muscle undergoes profound morphological and physiological changes associated with loss of strength, mass, and function, a condition known as sarcopenia. The aetiology of sarcopenia is complex and whilst research in this area is growing rapidly, there is a relative paucity of human studies, particularly in older women...

Placental neovascularization plays a crucial role in fetomaternal circulation throughout pregnancy and is dysregulated in several pregnancy-related diseases, including preeclampsia, gestational diabetes mellitus, and fetal growth restriction. Endothelial progenitor cells (EPCs) are a heterogeneous population of cells that differentiate into mature endothelial cells, which influence vascular homeostasis, neovascularization, and endothelial repair. Since their discovery in 1997 by Asahara et al., the role of EPCs in vascular biology has garnered a lot of interest...

O-Linked attachment of β-N-acetylglucosamine (O-GlcNAc) on serine and threonine residues of nuclear, cytoplasmic, and mitochondrial proteins is a highly dynamic and ubiquitous post-translational modification that impacts the function, activity, subcellular localization, and stability of target proteins. Physiologically, acute O-GlcNAcylation serves primarily to modulate cellular signaling and transcription regulatory pathways in response to nutrients and stress. To date, thousands of proteins have been revealed to be O-GlcNAcylated and this number continues to grow as the technology for the detection of O-GlcNAc improves...