KLK8 modulates macrophage function following myocardial infarction by promoting the paracrine of epidermal growth factor from cardiac fibroblasts.

Aims: Tissue kallikrein-related peptidase 8 (KLK8) plays a significant role in the regulation of cardiac remodeling following myocardial infarction (MI). However, the impact of KLK8 on macrophage (MΦ) function in the context of MI remains to be elucidated.

Materials And Methods: MI was induced through the ligation of the left anterior descending coronary artery for a duration of 1 h, followed by reperfusion.

Network pharmacology, molecular docking, and experimental verification reveal the mechanism of Yi-Shen-Hua-Shi granules treating acute kidney injury.

Ethnopharmacological Relevance: Yi-Shen-Hua-Shi granules (YSHSG) have been shown to improve kidney function in various renal disorders, which are characterized by the sudden decline and impairment of kidney function.

Aim Of The Study: To investigate the precise mechanisms and targets of YSHSG in combating sepsis-induced AKI.

Materials And Methods: Through network pharmacology, the active ingredients, main target proteins, and related signaling pathways of YSHSG in the treatment of sepsis-induced AKI were predicted.

Bradykinin attenuates endothelial-mesenchymal transition following cardiac ischemia-reperfusion injury.

Aims: Endothelial-mesenchymal transition (EndMT) is a crucial pathological process contributing to cardiac fibrosis. Bradykinin has been found to protect the heart against fibrosis. Whether bradykinin regulates EndMT has not been determined.

Tissue kallikrein-related peptidase8 accentuates cardiac fibrosis after myocardial ischemia-reperfusion injury via regulation of cardiac fibroblasts.

Aims: Tissue kallikrein-related peptidase8 (KLK8) has been found to mitigate acute myocardial ischemia-reperfusion (IR) injury. However, the effect of KLK8 on cardiac remodeling in response to IR injury has not been determined.

Materials And Methods: KLK8 overexpressing transgenic rat (KLK8-TG) was used as the animal model.

Upregulation of KLK8 contributes to CUMS-induced hippocampal neuronal apoptosis by cleaving NCAM1.

Neuronal apoptosis has been well-recognized as a critical mediator in the pathogenesis of depressive disorders. Tissue kallikrein-related peptidase 8 (KLK8), a trypsin-like serine protease, has been implicated in the pathogenesis of several psychiatric disorders. The present study aimed to explore the potential function of KLK8 in hippocampal neuronal cell apoptosis associated with depressive disorders in rodent models of chronic unpredictable mild stress (CUMS)-induced depression.

Phosphorylation by IKKβ Promotes the Degradation of HMGCL via NEDD4 in Lung Cancer.

Inflammation and metabolic reprogramming are hallmarks of cancer. How inflammation regulates cancer metabolism remains poorly understood. In this study, we found that 3-hydroxy-3-methylglutaryl-CoA lyase (HMGCL), the enzyme that catalyzes the catabolism of leucine and promotes the synthesis of ketone bodies, was downregulated in lung cancer.

Upregulation of contributes to lipopolysaccharide-induced pulmonary endothelial injury by induction of autophagy.

Background: Autophagy is activated during the pathogenesis of endothelial dysfunction and sepsis-associated acute lung injury (ALI). This study aimed to investigate whether autophagy affected endothelial barrier dysfunction and lung injury in a murine model of lipopolysaccharide (LPS)-induced ALI, and then further clarify whether forkhead box O1 (), an autophagy-related transcriptional factor, contributed to autophagy activation and ALI induced by LPS.

Methods: Male C57BL/6 mice were treated with LPS (30 mg/kg), and then were allocated to a control group and an LPS group with or without FOXO1 inhibitor (AS1842856) treatment, respectively.

Resveratrol alleviates acute lung injury through regulating PLSCR-3-mediated mitochondrial dysfunction and mitophagy in a cecal ligation and puncture model.

Sepsis is considered as a life-threatening organ dysfunction caused by a dysregulated response of the host to an infection. Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a life-threatening condition, and is the type of organ injury that is most commonly induced by sepsis. Resveratrol (RSV) has been shown to exert a wide range of therapeutic effects due to its anti-inflammatory and anti-oxidant properties.

Dexmedetomidine protects the heart against ischemia reperfusion injury via regulation of the bradykinin receptors.

Background: Dexmedetomidine (DEX) has been reported to protect the heart against ischemia reperfusion (I/R) injury. However, the exact mechanisms are still not fully understood.

Methods And Results: A rat cardiac I/R injury model was induced by ligation of the left anterior descending coronary artery for 1 h and subsequent reperfusion for 2 h, and DEX was administered intravenously 30 min before ischemia.

Spatial learning and memory deficits induced by prenatal glucocorticoid exposure depend on hippocampal CRHR1 and CXCL5 signaling in rats.

Background: Prenatal synthetic glucocorticoid (sGC) exposure increases the susceptibility to cognitive and affective disorders in postnatal life. We previously demonstrated that prenatal sGC exposure results in an increase in corticotropin-releasing hormone (CRH) receptor type 1 (CRHR1) expression in the hippocampus of rats, and CRHR1 is involved in synapse formation via regulation of C-X-C chemokine ligand 5 (CXCL5) in hippocampus. We sought to investigate that the roles of CRHR1 and CXCL5 in learning and memory impairment caused by prenatal sGC exposure.

A novel role of kallikrein-related peptidase 8 in the pathogenesis of diabetic cardiac fibrosis.

Among all the diabetic complications, diabetic cardiomyopathy, which is characterized by myocyte loss and myocardial fibrosis, is the leading cause of mortality and morbidity in diabetic patients. Tissue kallikrein-related peptidases (KLKs) are secreted serine proteases, that have distinct and overlapping roles in the pathogenesis of cardiovascular diseases. However, whether KLKs are involved in the development of diabetic cardiomyopathy remains unknown.

HS alleviates renal injury and fibrosis in response to unilateral ureteral obstruction by regulating macrophage infiltration via inhibition of NLRP3 signaling.

Renal fibrosis is a key pathological feature in chronic kidney diseases (CKDs). Dysregulation of hydrogen sulfide (HS) homeostasis is implicated in the pathogenesis of CKDs. Here, C57/BL6 mice were allocated to Sham and unilateral ureteral obstruction (UUO) groups, which were treated with NaHS or NLRP3 inflammasome inhibitor 16673-34-0 for 3-14 days.

Tissue kallikrein-related peptidase8 protects rat heart against acute ischemia reperfusion injury.

Tissue kallikrein-related peptidases (KLKs) play important roles in acute cardiac injury and cardiac remodeling. However, the exact cardiac actions of KLK8 have not been determined. Transgenic rat overexpressing KLK8 was established to examine the role of KLK8 in the heart.

miR-494 Contributes to Estrogen Protection of Cardiomyocytes Against Oxidative Stress Targeting (NF-κB) Repressing Factor.

Oxidative stress plays a pivotal role in the initiation and progression of cardiac diseases. Estrogens have been demonstrated to exert pleiotropic cardioprotective effects, among which antioxidative stress is one of the key effects linking estrogens to cardioprotection. By using a microRNAs (miRs) microarray screening approach, we discovered an increase in miR-494, which is known to exert cardioprotective effects, in estrogen-treated cardiomyocytes.

Endogenous HS resists mitochondria-mediated apoptosis in the adrenal glands via ATP5A1 S-sulfhydration in male mice.

In a previous study, we showed that endogenous hydrogen sulfide (HS) plays a key role in the maintenance of intact adrenal cortex function via the protection of mitochondrial function during endoxemia. We further investigated whether mitochondria-mediated apoptosis is involved in HS protection of adrenal function. LPS treatment resulted in mitochondria-mediated apoptosis in the adrenal glands of male mice, and these effects were prevented by the HS donor GYY4137.

Protective effects of resveratrol on mitochondrial function in the hippocampus improves inflammation-induced depressive-like behavior.

Growing evidence suggests that inflammatory processes may be involved in depressive disorders. Inflammation is known to induce mitochondrial dysfunction in the nervous system. However, whether mitochondrial dysfunction is involved in the occurrence of inflammation-induced depressive-like behavior remains to be investigated.

Upregulation of microRNA-22 contributes to myocardial ischemia-reperfusion injury by interfering with the mitochondrial function.

Mitochondrial oxidative damage is critically involved in cardiac ischemia reperfusion (I/R) injury. MicroRNA-22 (miR-22) has been predicted to potentially target sirtuin-1 (Sirt1) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α), both of which are known to provide protection against mitochondrial oxidative injury. The present study aims to investigate whether miR-22 is involved in the regulation of cardiac I/R injury by regulation of mitochondrial function.

Kallikrein-related peptidase 8 is expressed in myocardium and induces cardiac hypertrophy.

The tissue kallikrein-related peptidase family (KLK) is a group of trypsin- and chymotrypsin-like serine proteases that share a similar homology to parent tissue kallikrein (KLK1). KLK1 is identified in heart and has anti-hypertrophic effects. However, whether other KLK family members play a role in regulating cardiac function remains unknown.

Estrogens increase cystathionine-γ-lyase expression and decrease inflammation and oxidative stress in the myocardium of ovariectomized rats.

Objective: Hydrogen sulfide (H2S), generated in the myocardium predominantly via cystathionine-γ-lyase (CSE), is cardioprotective. The objectives of the present study were to investigate the effects of estrogens on CSE expression and H2S generation in the myocardium and to examine whether serum 17β-estradiol (E2) level is associated with CSE activity and H2S generation and whether H2S or E2 level is associated with proinflammatory cytokines and oxidative stress status.

Methods: Ovariectomized Sprague-Dawley rats received subcutaneous E2 (30 μg/kg/d) or vehicle for 12 weeks.