Activation of HIF-1α C-terminal transactivation domain promotes tubulointerstitial fibrosis through hexokinase 2-mediated metabolic reprogramming.

Background: The hypoxia-inducible factor-1α (HIF-1α), a master transcription factor for adaptive responses to hypoxia, possesses two transcriptional activation domains [TAD, N-terminal (NTAD) and C-terminal (CTAD)]. However, the exact effects of HIF-1α CTAD in chronic kidney disease (CKD) are poorly understood.

Methods: Here, two independent mouse models of hypoxia-induced CKD, including ischemia/reperfusion-induced kidney injury and unilateral ureteral obstruction-induced nephropathy, were established using HIF-1α CTAD knockout (HIF-1α CTAD) mice.

Tubule-specific cyclin-dependent kinase 12 knockdown potentiates kidney injury through transcriptional elongation defects.

Direct tubular injury caused by several medications, especially chemotherapeutic drugs, is a common cause of AKI. Inhibition or loss of cyclin-dependent kinase 12 (CDK12) triggers a transcriptional elongation defect that results in deficiencies in DNA damage repair, producing genomic instability in a variety of cancers. Notably, 10-25% of individuals developed AKI after treatment with a CDK12 inhibitor, and the potential mechanism is not well understood.

Quercetin alleviates tubulointerstitial inflammation by inhibiting exosomes-mediated crosstalk between tubular epithelial cells and macrophages.

Background: Tubulointerstitial inflammation (TII) is a critical pathological feature of kidney disease leading to renal fibrosis, and its treatment remains a major clinical challenge. We sought to explore the role of quercetin, a potential exosomes inhibitor, in exosomes release and TII.

Methods: The effects of quercetin on exosomes release and TII were examined by two TII mouse models: the unilateral ureteral obstruction (UUO) models and the LPS-induced mouse models.

Fisetin mitigates hepatic ischemia-reperfusion injury by regulating GSK3β/AMPK/NLRP3 inflammasome pathway.

Background: Hepatic ischemia-reperfusion (I/R) injury (IRI) represents a crucial challenge in liver transplantation. Fisetin has anti-inflammatory, anti-aging and anti-oxidative properties. This study aimed to examine whether fisetin mitigates hepatic IRI and examine its underlying mechanisms.

NLRC3 alleviates hypoxia/reoxygenation induced inflammation in RAW264.7 cells by inhibiting K63-linked ubiquitination of TRAF6.

Background: NOD-like receptor family CARD domain containing 3 (NLRC3) plays an important role in both innate and adaptive immunity. This study was to explore the function and related mechanisms of NLRC3 in a hypoxia/reoxygenation (H/R)-induced inflammatory response in RAW264.7 cells.

Succinate ester derivative of δ-tocopherol enhances the protective effects against Co γ-ray-induced hematopoietic injury through granulocyte colony-stimulating factor induction in mice.

α-tocopherol succinate (α-TOS), γ-tocotrienol (GT3) and δ-tocotrienol (DT3) have drawn large attention due to their efficacy as radioprotective agents. α-TOS has been shown to act superior to α-tocopherol (α-TOH) in mice by reducing lethality following total body irradiation (TBI). Because α-TOS has been shown to act superior to α-tocopherol (α-TOH) in mice by reducing lethality following total body irradiation (TBI), we hypothesized succinate may be contribute to the radioprotection of α-TOS.

MR venography of the inferior mesentery vein.

Objective: To evaluate on three-dimensional (3D) dynamic contrast-enhanced (DCE) MR venography (MRV), the visibility of the inferior mesenteric vein (IMV), its insertion pattern into the portal system, and the difference of IMV diameters between healthy subjects and patients with cirrhosis.

Materials And Methods: Two hundred and seventeen consecutive patients who had abdominal 3D DCE MRI was included in this study. The original image data of 3D DCE MRI was used to generate multiple planar volume reconstruction (MPVR) images, which were evaluated for visualization of the IMV and its pattern of insertion into the portal system.