Long-term hyperuricemia can induce kidney damage, clinically referred to as hyperuricemic nephropathy (HN), which is characterized by renal fibrosis, inflammation, and oxidative stress. However, currently used uric acid-lowering drugs are not capable of protecting the kidneys from damage. Therefore, uric acid-lowering drugs that can also protect the kidneys are urgently needed.
View Article and Find Full Text PDFDysregulation of NLRP3 inflammasome results in uncontrolled inflammation, which participates in various chronic diseases. TWIK2 potassium channel mediates potassium efflux that has been reported to be an essential upstream mechanism for ATP-induced NLRP3 inflammasome activation. Thus, TWIK2 potassium channel could be a potential drug target for NLRP3-related inflammatory diseases.
View Article and Find Full Text PDFThe antioxidant defense system in malignant cells, which involves antioxidant enzymes and antioxidant molecules, is an innate barrier to photodynamic therapy (PDT). Because of the complexity of the endogenous antioxidant mechanisms of these cells, simply inhibiting individual antioxidant pathways has a limited effect on improving the lethality of ROS. To enhance the efficacy of PDT for tumor treatment, a versatile nanoparticle (NP)-based drug is developed, which the authors call PZB NP, containing the glutathione inhibitor l-buthionine sulfoximine (BSO) and the heme oxygenase 1 (HO-1) inhibitor protoporphyrin zinc(II) (ZnPP) to suppress the innate antioxidant defense system of cancer cells in a two-pronged manner.
View Article and Find Full Text PDFUrate transporter 1 (URAT1) and glucose transporter 9 (GLUT9) are important targets for the development of uric acid-lowering drugs. We previously showed that the flexible linkers of URAT1 inhibitors could enhance their potency. In this study we designed and synthesized CDER167, a novel RDEA3710 analogue, by introducing a linker (methylene) between the naphthalene and pyridine rings to increase flexibility, and characterized its pharmacological and pharmacokinetics properties in vitro and in vivo.
View Article and Find Full Text PDFACS Appl Mater Interfaces
November 2018
Breast cancer is the second cause of cancer mortality in women globally. Early detection, treatment, and metastasis monitoring are of great importance to favorable prognosis. Although conventional diagnostic methods, such as breast X-ray mammography and image positioning biopsy, are accurate, they could cause radioactive or invasive damage to patients.
View Article and Find Full Text PDFHyperpolarization-activated cyclic nucleotide-gated (HCN) channels play a critical role in controlling pacemaker activity in both heart and nervous system. Developing HCN channel inhibitors has been proposed to be an important strategy for the treatment of pain, heart failure, arrhythmias, and epilepsy. One HCN channel inhibitor, ivabradine, has been clinically approved for the treatment of angina pectoris and heart failure.
View Article and Find Full Text PDFTwo water-stable three-dimensional Mn- and Gd-based metal-organic frameworks (MOFs), {[Mn(Cmdcp)(HO)]·HO} (1) and {[Gd(Cmdcp)(HO)](NO)·3HO} (2, HCmdcpBr = N-(4-carboxy benzyl)-(3,5-dicarboxyl)pyridinium bromide), have been prepared and analyzed. In vitro magnetic resonance imaging indicated that MOFs 1 and 2 possess relaxivity r values of 17.50 and 13.
View Article and Find Full Text PDFRecombinant tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), as a novel cancer therapeutic, is being tested in phase II and III clinical trials; however, TRAIL resistance remains a big obstacle preventing its clinical application. Considering that TRAIL-induced apoptosis through death receptors DR4 and DR5, their activation may be an alternative pathway to suppress TRAIL resistance. In this study, a negative correlation between DR5 expression and TRAIL resistance was observed, and miR-133a was predicted to be the most promising candidate to suppress DR5 expression.
View Article and Find Full Text PDFAs deubiquitinases, several ubiquitin specific protease members have been reported to mediate tumorigenesis. Although ubiquitin specific protease 5 (Usp5) was previously demonstrated to suppress p53 transcriptional activity and DNA repair, its role in carcinogenesis remains elusive. In this study, we sought to define a novel role of Usp5 in tumorigenesis.
View Article and Find Full Text PDFHpn is a small histidine-rich cytoplasmic protein from Helicobacter pylori and has been recognized as a high-risk factor for several cancers including gastric cancer, colorectal cancer, and MALT lymphoma. However, the relationship between Hpn and cancers remains elusive. In this study, we discovered that Hpn protein effectively suppressed cell growth and induced apoptosis in hepatocellular carcinoma (HCC).
View Article and Find Full Text PDFColorectal cancer (CRC) is a common malignancy, most of which remain unresponsive to chemotherapy. As one of the earliest cytotoxic drugs, methotrexate (MTX) serves as an anti-metabolite and anti-folate chemotherapy for various cancers. Unfortunately, MTX resistance prevents its clinical application in cancer therapy.
View Article and Find Full Text PDFFourteen 3-methyl-3,7-dihydro-purine-2,6-dione derivatives 1-14 bearing carboxybenzyl and 2-chloro/cyanobenzyl groups at the N-1 and N-7 positions, respectively, were synthesized as dipeptidyl peptidase IV (DPP-IV) inhibitors. These compounds were characterized on the basis of NMR ((1)H and (13)C) and ESI MS data. In vitro bioassay indicates that most of these compounds showed moderate to good inhibitory activities against DPP-IV.
View Article and Find Full Text PDFBackground: Recently, evidence indicated that the rapamycin-eluting stent which was used worldwide may contribute to an increased risk for thrombosis. On the contrary, other researchers found it was safe. Thus, it is necessary to clarify the effect of rapamycin on thrombosis and the corresponding mechanisms.
View Article and Find Full Text PDFPlumbagin (PLB) has shown anti-cancer activity but the mechanism is unclear. This study has found that PLB has a potent pro-apoptotic and pro-autophagic effect on A549 and H23 cells. PLB arrests cells in G2/M phase, and increases the intracellular level of reactive oxygen species in both cell lines.
View Article and Find Full Text PDFZhonghua Bing Li Xue Za Zhi
October 2012
Objective: To study the clinicopathological features of diabetic microangiopathy in liver and diabetic hepatosclerosis (DHS) of elderly male with type 2 diabetes mellitus (T2DM).
Methods: One hundred and twenty autopsy cases with T2DM (diabetic group) and contemporary 48 cases, non-diabetic and glucose tolerance abnormal, matched by gender and age (control group) were selected in the study. Cases with the cirrhosis and fibrosis of liver caused by other foregone etiological factors were excluded.
Zhonghua Yi Xue Za Zhi
September 2012
Objective: To enhance the understandings of clinical, radiological and pathological features of hypersensitivity pneumonitis (HP).
Methods: Six HP cases with pathological data, clinical and radiological data were retrospectively analyzed during the period from February 2009 to September 2011 at Beijing Hospital of Ministry of Health. There were 2 males and 4 females with a mean age of 51.
Praeruptorin A (PA) is a pyranocoumarin compound isolated from the dried root of Peucedanum praeruptorum Dunn (Umbelliferae). However, the antiinflammatory effect of PA has not been reported. The present study investigated the antiinflammatory effect of PA in lipopolysaccharide (LPS)-stimulated RAW 264.
View Article and Find Full Text PDFAim: Hepatic glycogen phosphorylase (GP) and glucose-6-phosphatase (G6Pase) are important in control of blood glucose homeostasis, and are considered to be potential targets for antidiabetic drugs. Astragaloside IV has been reported to have a hypoglycemic effect. However, the biochemical mechanisms by which astragaloside IV regulates hepatic glucose-metabolizing enzymes remain unknown.
View Article and Find Full Text PDFNan Fang Yi Ke Da Xue Xue Bao
April 2009
Objective: To construct a bait plasmid containing human telomerase RNA with multiple point mutations in a yeast three-hybrid system and evaluate the toxicity of the recombinant bait plasmid.
Methods: The primers were designed according to the hTR sequence and the target mutation sites for inducing T-->A mutations at the 41st, the 80th and 102nd nucleotides of the hTR gene using the overlapping extension PCR (OE-PCR) method. The mutant was cloned into PMD18T vector, confirmed by sequencing, sub-cloned into the bait plasmid PRH3' and identified with PCR and restriction enzyme digestion.
Aim: Exocytosis of endothelial Weibel-Palade bodies, which contain von Willebrand factor (VWF), P-selectin and other modulators, plays an important role in both inflammation and thrombosis. The present study investigates whether genipin, an aglycon of geniposide, inhibits endothelial exocytosis.
Methods: Human umbilical vein endothelial cells (HUVECs) were isolated from umbilical cords and cultured.
Ezrin, encoded by VIL2, is a membrane-cytoskeletal linker protein that has been suggested to be involved in tumorigenesis. Ezrin expression in esophageal squamous cell carcinoma (ESCC) was described recently, but its clinical significance and the molecular mechanism underlying its regulated expression remain unclear. Thus, we retrospectively evaluated ezrin expression by immunohistochemistry in a tissue microarray representing 193 ESCCs.
View Article and Find Full Text PDFZhonghua Bing Li Xue Za Zhi
May 2006
Objective: To study the clinicopathologic characteristics of metastatic carcinomas to the spleen.
Methods: Sixteen cases of metastatic carcinoma to the spleen were retrieved from archival clinical, surgical pathology and autopsy records. The demographic data (including sex and age of patients), clinical symptoms, primary sites, tumor histologic types, gross appearance of spleen and growth patterns within the spleen were analyzed.
Objective: To observe the functional changes of dendritic cells (DCs) after infection by recombinant retrovirus carrying human telomerase reverse transcriptase (hTERT) gene fragment.
Methods: Interleukin-12 (IL-12) levels in DC culture supernatant was determined by enzyme-linked immunosorbent assay (ELISA). The abilities of DCs infected with recombinant retrovirus carrying hTERT gene (hTERT-DCs) and non-infected DCs (N-DCs) to stimulate allogeneic lymphocyte proliferation were evaluated with mixed leukocytes reaction (MLR), and the surface markers of DCs including CD80, CD83, CD86 and HLA-DR were detected by flow cytometry.