Endometrial carcinoma with cervical stromal invasion: Three case reports.

Background: Endometrial cancer is a kind of well-known tumors of female genitourinary system. Cervical stromal invasion is an adverse factor for poor prognosis of endometrial cancer. There is still controversy regarding the use of magnetic resonance imaging (MRI) in the diagnosis of cervical stromal invasion of endometrial cancer.

Altered counts and mitochondrial mass of peripheral blood leucocytes in patients with chronic hepatitis B virus infection.

Hepatitis B virus (HBV) damages liver cells through abnormal immune responses. Mitochondrial metabolism is necessary for effector functions of white blood cells (WBCs). The aim was to investigate the altered counts and mitochondrial mass (MM) of WBCs by two novel indicators of mitochondrial mass, MM and percentage of low mitochondrial membrane potential, MMP%, due to chronic HBV infection.

Discovery of novel diaryl substituted isoquinolin-1(2H)-one derivatives as hypoxia-inducible factor-1 signaling inhibitors for the treatment of rheumatoid arthritis.

Since synovial hypoxic microenvironment significantly promotes the pathological progress of rheumatoid arthritis (RA), hypoxia-inducible factor 1 (HIF-1) has been emerged as a promising target for the development of novel therapeutic agents for RA treatment. In this study, we designed and synthesized a series of diaryl substituted isoquinolin-1(2H)-one derivatives as HIF-1 signaling inhibitors using scaffold-hopping strategy. By modifying the substituents on N-atom and 6-position of isoquinolin-1-one, we discovered compound 17q with the most potent activities against HIF-1 (IC = 0.

Targeted inhibition of transforming growth factor-β type I receptor by AZ12601011 improves paraquat poisoning-induced multiple organ fibrosis.

Paraquat (PQ) causes fatal poisoning that leads to systemic multiple organ fibrosis, and transforming growth factor (TGF)-β1 plays a critical role in this process. In this study, we aimed to investigate the effects of AZ12601011 (a small molecular inhibitor of TGFβRI) on PQ-induced multiple organ fibrosis. We established a mouse model of PQ in vivo and used PQ-treated lung epithelial cell (A549) and renal tubular epithelial cells (TECs) in vitro.

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.

Therapeutic effects of shikonin on adjuvant-induced arthritis in rats and cellular inflammation, migration and invasion of rheumatoid fibroblast-like synoviocytes via blocking the activation of Wnt/β-catenin pathway.

Background: Shikonin (SKN), the main bioactive component isolated from Lithospermum erythrorhizon Sieb et Zucc, has multiple activities including anti-rheumatic effect, but its specific roles and the precise mechanisms in regulating biological properties of rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) are unclear and need further clarification.

Purpose: This study explored the therapeutic roles of SKN on rat adjuvant-induced arthritis (AIA) and cellular inflammation, migration and invasion of TNF-α-induced RA FLS (MH7A cells), and further demonstrated the involved mechanisms.

Methods: SKN was intraperitoneally given to AIA rats and its therapeutic role was valued.

Simulation and optimization of scrap wagon dismantling system based on Plant Simulation.

Based on the existing plant layout and process flow, a simulation analysis was conducted using the Plant Simulation platform with the utilization efficiency of each station and production capacity of the dismantling system as indicators. A problem with long-term suspension in the disassembly process was determined. Based on the two optimization directions of increasing material transportation equipment and expanding the buffer capacity, a cost-oriented optimization model is established.

Global trend and future landscape of intestinal microcirculation research from 2000 to 2021: A scientometric study.

Background: The intestinal microcirculation functions in food absorption and metabolic substance exchanges. Accumulating evidence indicates that intestinal microcirculatory dysfunction is a significant source of multiple gastrointestinal diseases. To date, there has not been a scientometric analysis of intestinal microcirculatory research.

Role of insulin in pancreatic microcirculatory oxygen profile and bioenergetics.

Background: The pancreatic islet microcirculation adapts its metabolism to cope with limited oxygen availability and nutrient delivery. In diabetes, the balance between oxygen delivery and consumption is impaired. Insulin has been proven to exert complex actions promoting the maintenance of homeostasis of the pancreas under glucotoxicity.

RIPK3 inhibitor-AZD5423 alleviates acute kidney injury by inhibiting necroptosis and inflammation.

Acute kidney injury (AKI) is a clinical syndrome that is defined as a sudden decline in renal function and characterized by inflammation and programmed cell death of renal tubular epithelial cells. Necroptosis is a form of regulated cell death that requires activation of receptor interacting protein kinase 3 (RIPK3) and its phosphorylation of the substrate MLKL. RIPK3 plays an important role in acute kidney injury, and hence developing its inhibitors is considered as one of the promising strategies aimed at prevention and treatment of AKI.

Design and Synthesis of a 2-Amino-pyridine Derivative as a Potent CDK8 Inhibitor for Anti-colorectal Cancer Therapy.

CDK8 is a transcriptional cyclin-dependent kinase and considered as a potential target in colon cancer therapeutics. Here, a novel selective CDK8 inhibitor was identified against colon cancer . Specifically, based on the structural information of the sorafenib-bound CDK8 structure, a series of novel 2-amino-pyridine derivatives were designed, synthesized, and evaluated.

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.

Hypertension and clinical outcomes in patients with familial hypercholesterolemia.

Background: Hypertension is a known risk factor for cardiovascular disease; however, its impact on clinical outcomes in patients with heterozygous familial hypercholesterolemia (HeFH) is unclear. Hence, we aimed to investigate the effects of hypertension on severity of coronary artery atherosclerosis and cardiovascular outcomes in patients with HeFH.

Methods: A total of 480 patients with clinical or molecular diagnosis of definite or probable familial hypercholesterolemia according to Dutch Lipid Clinic Network criteria (DLCN score ≥6) were included in the study.

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.

SORBS2 as a molecular target for atherosclerosis in patients with familial hypercholesterolemia.

Background: Familial hypercholesterolemia (FH) is a metabolic disease in which patients are prone to develop premature atherosclerosis (AS). Sorbin and SH3 Domain Containing 2 (SORBS2) is known to play a role in coronary heart disease (CHD). However, the mechanism underlying SORBS2 involvement in the development of hypercholesterolemia remains unknown.

A novel small molecule Hsp90 inhibitor, C-316-1, attenuates acute kidney injury by suppressing RIPK1-mediated inflammation and necroptosis.

Acute kidney injury (AKI) is marked by a fast deterioration of the kidney function that may be caused by a variety of factors. Recently, although our group found that PPBICA alleviated programmed cell death in AKI, poor water solubility limited its bioavailability. In this research, we screened a series of derivatives and found that C-316-1 had the best suppressive effect on preventing necroptosis and inflammation in cisplatin- and ischemia/reperfusion-induced AKI in vitro and in vivo with lower toxicity and better water solubility.

Discovery of a chalcone derivative as potent necroptosis inhibitor for the treatment of acute kidney injury.

Necroptosis, a form of inflammation-related programmed cell death, is a major mechanism of proximal tubular cell injury in acute kidney injury (AKI). Blockade of necroptosis signalling represents a promising strategy for clinical therapy of AKI. Previously, we identified a small molecular receptor-interacting protein kinases (RIPK)1 inhibitor Cpd-71 with nephroprotective activities.

Inhibition of attenuates renal injury and inflammation by alleviating m6A modifications via IGF2BP2-dependent mechanisms.

The role of -methyladenosine (m6A) modifications in renal diseases is largely unknown. Here, we characterized the role of -adenosine-methyltransferase-like 3 (METTL3), whose expression is elevated in renal tubules in different acute kidney injury (AKI) models as well as in human biopsies and cultured tubular epithelial cells (TECs). silencing alleviated renal inflammation and programmed cell death in TECs in response to stimulation by tumor necrosis factor-α (TNF-α), cisplatin, and lipopolysaccharide (LPS), whereas overexpression had the opposite effects.

Synthesis and biological evaluation of novel hybrids of phenylsulfonyl furoxan and phenstatin derivatives as potent anti-tumor agents.

Hybridization of nitric oxide (NO) donors with known anti-cancer agents have been emerged as a strategy to achieve improved therapeutic effect and to overcome chemo-resistance in cancer therapy. In this study, furoxan moiety as an efficient NO donor was introduced to phenstatin, a microtubule-interfering agent (MIA), leading to the design and synthesis of a series of furoxan-based NO-releasing arylphenones derivatives. In biological evaluation, the synthesized compounds showed moderate to potent anti-tumor activities against several human cancer cell lines.