Aurantiamide mitigates acute kidney injury by suppressing renal necroptosis and inflammation via GRPR-dependent mechanism.

Acute kidney injury (AKI) manifests as a clinical syndrome characterised by the rapid accumulation of metabolic wastes, such as blood creatinine and urea nitrogen, leading to a sudden decline in renal function. Currently, there is a lack of specific therapeutic drugs for AKI. Previously, we identified gastrin-releasing peptide receptor (GRPR) as a pathogenic factor in AKI.

Cpd-A1 alleviates acute kidney injury by inhibiting ferroptosis.

Acute kidney injury (AKI) is defined as sudden loss of renal function characterized by increased serum creatinine levels and reduced urinary output with a duration of 7 days. Ferroptosis, an iron-dependent regulated necrotic pathway, has been implicated in the progression of AKI, while ferrostatin-1 (Fer-1), a selective inhibitor of ferroptosis, inhibited renal damage, oxidative stress and tubular cell death in AKI mouse models. However, the clinical translation of Fer-1 is limited due to its lack of efficacy and metabolic instability.

Mild hypothermia reduces lipopolysaccharide-induced microglial activation via down-regulation of Tent5c.

Microglial activation is a critical factor in the pathogenesis and progression of neuroinflammatory diseases. Mild hypothermia, known for its neuroprotective properties, has been shown to alleviate microglial activation. In this study, we explore the differentially expressed (DE) mRNAs and long non-coding RNAs (lncRNAs) in BV-2 microglial cells under different conditions: normal temperature (CN), mild hypothermia (YT), normal temperature with lipopolysaccharide (LPS), and mild hypothermia with LPS (LPS + YT).

Madecassoside alleviates acute kidney injury by regulating JNK-mediated oxidative stress and programmed cell death.

Background: Acute kidney injury (AKI) has high morbidity and mortality, which is manifested by inflammation and apoptosis. Effective treatment methods for AKI are currently lacking.

Objective: This study demonstrated the protecting effects of Madecassoside (MA) in the cisplatin- and hypoxia-reoxygenation-induced renal tubular epithelial cells in vitro and AKI mice in vivo.

Novel insights into STAT3 in renal diseases.

Signal transducer and activator of transcription 3 (STAT3) is a cell-signal transcription factor that has attracted considerable attention in recent years. The stimulation of cytokines and growth factors can result in the transcription of a wide range of genes that are crucial for several cellular biological processes involved in pro- and anti-inflammatory responses. STAT3 has attracted considerable interest as a result of a recent upsurge in study because of their role in directing the innate immune response and sustaining inflammatory pathways, which is a key feature in the pathogenesis of many diseases, including renal disorders.

Compound-42 alleviates acute kidney injury by targeting RIPK3-mediated necroptosis.

Background And Purpose: Necroptosis plays an essential role in acute kidney injury and is mediated by receptor-interacting protein kinase 1 (RIPK1), receptor-interacting protein kinase 3 (RIPK3), and mixed lineage kinase domain-like pseudokinase (MLKL). A novel RIPK3 inhibitor, compound 42 (Cpd-42) alleviates the systemic inflammatory response. The current study was designed to investigate whether Cpd-42 exhibits protective effects on acute kidney injury and reveal the underlying mechanisms.

Role of epigenetically regulated inflammation in renal diseases.

In recent decades, renal disease research has witnessed remarkable advances. Experimental evidence in this field has highlighted the role of inflammation in kidney disease. Epigenetic dynamics and immunometabolic reprogramming underlie the alterations in cellular responses to intrinsic and extrinsic stimuli; these factors determine cell identity and cell fate decisions and represent current research hotspots.

Cpd-0225 attenuates renal fibrosis via inhibiting ALK5.

Chronic kidney disease (CKD) is an increasing public health concern, characterized by a reduced glomerular filtration rate and increased urinary albumin excretion. Renal fibrosis is an important pathological condition in patients with CKD. In this study, we evaluated the anti-fibrotic effect of Cpd-0225, a novel transforming growth factor-β (TGF-β) type I receptor (also known as ALK5) inhibitor, in vitro and in vivo, by comparing its effect with that of SB431542, a classic ALK5 inhibitor, which has not entered the clinical trial stage owing to multiple side effects.

Protective effect of inhibiting necroptosis on gentamicin-induced nephrotoxicity.

Necroptosis is defined as a novel programmed cell necrosis that is mediated by receptor interacting serine-threonine protein kinase 1 (RIPK1) and other related signals. Necrosis, apoptosis and inflammation are commonly considered as the leading mechanism in acute kidney injury (AKI) induced by gentamicin (GEN), which is a useful antibiotic for treating the infection of Gram-negative bacterial. However, the necroptosis in the pathogenesis of GEN-induced AKI is unknown.

Targeted inhibition of TGF-β type I receptor by AZ12601011 protects against kidney fibrosis.

Renal fibrosis, a common feature of chronic kidney disease, causes the progressive loss of renal function, in which TGF-β plays a critical role. In this study, we found that expression levels of TGF-β and its receptor 1 (TGF-βR1) were both significantly increased in obstructive fibrosis kidneys. AZ12601011 is a small molecular inhibitor of TGF-βR1; however, its therapeutic potential for renal fibrosis remains unclear.

Insulin-like growth factor binding protein 7 promotes acute kidney injury by alleviating poly ADP ribose polymerase 1 degradation.

The novel biomarker, insulin-like growth factor binding protein 7 (IGFBP7), is used clinically to predict different types of acute kidney injury (AKI) and has drawn significant attention as a urinary biomarker. However, as a secreted protein in the circulation of patients with AKI, it is unclear whether IGFBP7 acts as a key regulator in AKI progression, and if mechanisms underlying its upregulation still need to be determined. Here we found that IGFBP7 is highly expressed in the blood and urine of patients and mice with AKI, possibly via a c-Jun-dependent mechanism, and is positively correlated with kidney dysfunction.

The protective effect of rabeprazole on cisplatin-induced apoptosis and necroptosis of renal proximal tubular cells.

Nephrotoxicity is a major adverse reaction of cisplatin-based chemotherapy. Organic cation transporter 2 (OCT2) which is located on the basement membrane of human proximal renal tubules is responsible for the renal accumulation of cisplatin and its nephrotoxicity. This study aimed to investigate the protective effect of PPIs to CP-induced nephrotoxicity.

The Programmed Cell Death of Macrophages, Endothelial Cells, and Tubular Epithelial Cells in Sepsis-AKI.

Sepsis is a systemic inflammatory response syndrome caused by infection, following with acute injury to multiple organs. Sepsis-induced acute kidney injury (AKI) is currently recognized as one of the most severe complications related to sepsis. The pathophysiology of sepsis-AKI involves multiple cell types, including macrophages, vascular endothelial cells (ECs) and renal tubular epithelial cells (TECs), etc.

Gypenoside XLIX protects against acute kidney injury by suppressing IGFBP7/IGF1R-mediated programmed cell death and inflammation.

Background: Acute kidney injury (AKI), characterised by excessive inflammatory cell recruitment and programmed cell death, has a high morbidity and mortality; however, effective and specific therapies for AKI are still lacking.

Objective: This study aimed to evaluate the renoprotective effects of gypenoside XLIX (Gyp XLIX) in AKI.

Methods: The protective effects of Gyp XLIX were tested in two AKI mouse models established using male C57BL/6 mice (aged 6-8 weeks) by a single intraperitoneal injection of cisplatin (20 mg/kg) or renal ischemia-reperfusion for 40 min.

Rutaecarpine derivative Cpd-6c alleviates acute kidney injury by targeting PDE4B, a key enzyme mediating inflammation in cisplatin nephropathy.

Acute kidney injury (AKI), characterized by a rapid decline in renal function, is triggered by an acute inflammatory response that leads to kidney damage. An effective treatment for AKI is lacking. Using in vitro and in vivo AKI models, our laboratory has identified a series of anti-inflammatory molecules and their derivatives.

Dexmedetomidine inhibits the invasion, migration, and inflammation of rheumatoid arthritis fibroblast-like synoviocytes by reducing the expression of NLRC5.

Rheumatoid arthritis (RA) is a chronic, autoimmune disease characterized by inflammatory synovitis, but its pathogenesis remains unclear. NLRC5 is a newly discovered member of the NLR family that is effective in regulating autoimmunity, inflammatory responses, and cell death processes. Dexmedetomidine (DEX) has been reported to have a variety of pharmacological effects, including anti-inflammatory and analgesic effects.

Smad3 promotes AKI sensitivity in diabetic mice via interaction with p53 and induction of NOX4-dependent ROS production.

The incidence and severity of acute kidney injury (AKI) is increased yearly in diabetic patients. Although the mechanisms for this remain unclear, the prevention of AKI in diabetic nephropathy is feasible and of value. As we detected highly activation of TGF-β/Smad3 signaling in both human biopsy and mouse model of diabetic nephropathy, we hypothesized that Smad3 activation in diabetic kidneys may increase AKI sensitivity.

Alcohol promotes renal fibrosis by activating Nox2/4-mediated DNA methylation of Smad7.

Alcohol consumption causes renal injury and compromises kidney function. The underlying mechanism of the alcoholic kidney disease remains largely unknown. In the present study, an alcoholic renal fibrosis animal model was first employed which mice received liquid diet containing alcohol for 4 to 12 weeks.

Over-Expression of PTEN Suppresses the Proliferation and Migration of Fibroblast-Like Synoviocytes in Adjuvant-Induced Arthritis.

Background/aims: Rheumatoid arthritis (RA) is characterized by a tumor-like expansion of the synovium and the subsequent destruction of adjacent articular cartilage and bone. Recent studies have shown that phosphatase and tension homolog deleted on chromosome 10 (PTEN) might contribute to the surviva of fibroblast-like synoviocytes (FLSs) and the production of pro-inflammatory cytokines in RA. The purpose of this study was to explore the functions and underlying mechanisms of PTEN in the proliferation and migration of FLSs.

Metastasis-associated in colon cancer 1: A promising biomarker for the metastasis and prognosis of colorectal cancer.

Colorectal cancer (CRC) is the fourth most frequent type of malignancy in the world. Metastasis accounts for >90% mortalities in patients with CRC. The metastasis-associated in colon cancer 1 (MACC1) gene has been identified as a novel biomarker for the prediction of metastasis and disease prognosis, particularly for patients with early-stage disease.

Pharmacogenomics research: a potential strategy for drug development.

Adverse drug reactions (ADR) and drug ineffectiveness are the common in clinical practice. Recent studies have indicated their strong connection to the genetic feature of patients. To further illustrate this relationship, the discipline of Pharmacogenomics (PGx) was born.