Potential of a Novel Chemical Compound Targeting Matrix Metalloprotease-13 for Early Osteoarthritis: An In Vitro Study

Osteoarthritis is a progressive disease characterized by cartilage destruction in the joints. Matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs) play key roles in osteoarthritis progression. In this study, we screened a chemical compound library to identify new drug candidates that target MMP and ADAMTS using a cytokine-stimulated OUMS-27 chondrosarcoma cells. By screening PCR-based mRNA expression, we selected 2-(8-methoxy-2-methyl-4-oxoquinolin-1(4H)-yl)-N-(3-methoxyphenyl) acetamide as a potential candidate. We found that 2-(8-methoxy-2-methyl-4-oxoquinolin-1(4H)-yl)-N-(3-methoxyphenyl) acetamide attenuated IL-1 beta-induced MMP13 mRNA expression in a dose-dependent manner, without causing serious cytotoxicity. Signaling pathway analysis revealed that 2-(8-methoxy-2-methyl-4-oxoquinolin-1(4H)-yl)-N-(3-methoxyphenyl) acetamide attenuated ERK- and p-38-phosphorylation as well as JNK phosphorylation. We then examined the additive effect of 2-(8-methoxy-2-methyl-4-oxoquinolin-1(4H)-yl)-N-(3-methoxyphenyl) acetamide in combination with low-dose betamethasone on IL-1 beta-stimulated cells. Combined treatment with 2-(8-methoxy-2-methyl-4-oxoquinolin-1(4H)-yl)-N-(3-methoxyphenyl) acetamide and betamethasone significantly attenuated MMP13 and ADAMTS9 mRNA expression. In conclusion, we identified a potential compound of interest that may help attenuate matrix-degrading enzymes in the early osteoarthritis-affected joints

An interspecific linkage map of SSR and intronic polymorphism markers in tomato

Despite the collection and availability of abundant tomato genome sequences, PCR-based markers adapted to large scale analysis have not been developed in tomato species. Therefore, using public genome sequence data in tomato, we developed three types of DNA markers: expressed sequence tag (EST)-derived simple sequence repeat (SSR) markers (TES markers), genome-derived SSR markers (TGS markers) and EST-derived intronic polymorphism markers (TEI markers). A total of 2,047 TES, 3,510 TGS and 674 TEI markers were established and used in the polymorphic analysis of a cultivated tomato (Solanum lycopersicum) ‘LA925’ and its wild relative Solanum pennellii ‘LA716’, parents of the Tomato-EXPEN 2000 mapping population. The polymorphic ratios between parents revealed by the TES, TGS and TEI markers were 37.3, 22.6 and 80.0%, respectively. Those showing polymorphisms were used to genotype the Tomato-EXPEN 2000 mapping population, and a high-density genetic linkage map composed of 1,433 new and 683 existing marker loci was constructed on 12 chromosomes, covering 1,503.1 cM. In the present map, 48% of the mapped TGS loci were located within heterochromatic regions, while 18 and 21% of TES and TEI loci, respectively, were located in heterochromatin. The large number of SSR and SNP markers developed in this study provide easily handling genomic tools for molecular breeding in tomato. Information on the DNA markers developed in this study is available at http://www.kazusa.or.jp/tomato/

Increased Glycine-conjugated and Unconjugated Bile Acid Levels Associated with Aggravation of Nonalcoholic Steatohepatitis and Cardiovascular Disease in SHRSP5/Dmcr Rat

The SHRSP5/Dmcr is a useful animal model for the development of nonalcoholic steatohepatitis (NASH) pathology when fed a high-fat, high-cholesterol diet, and further drug interventions can lead to concomitant cardiovascular disease. While SHRSP5/Dmcr rats have been used for basic research related to NASH, details of their bile acid metabolism in this condition are unknown. In this study, we aimed to clarify the changes in the serum bile acid (BA) fractions associated with NASH and found that glycine-conjugated and unconjugated bile acid increased with worsening NASH and cardiovascular disease while taurine-conjugated BA relatively decreased

Combined resection of the transpancreatic common hepatic artery preserving the gastric arterial arcade without arterial reconstruction in hepatopancreatoduodenectomy: a case report

Abstract Background Surgeons sometimes must plan pancreatoduodenectomy (PD) for patients with a variant common hepatic artery (CHA) branching from the superior mesenteric artery (SMA) penetrating the pancreatic parenchyma, known as a transpancreatic CHA (tp-CHA). Case presentation A 67-year-old man was admitted to our hospital because of liver dysfunction. A duodenal tumor was identified by gastrointestinal endoscopy, and a biopsy revealed a neuroendocrine tumor. Computed tomography showed multiple metastases in the left three sections of the liver. As an anatomical variant, the CHA branched from the SMA and passed through the parenchyma of the pancreatic head, and all hepatic arteries branched from the CHA. Furthermore, the arcade between the left and right gastric artery (RGA) was detected, and the RGA branched from the root of the left hepatic artery. PD and left trisectionectomy of the liver were performed. The tp-CHA was resected with the pancreatic head, and the gastric arterial arcade was preserved to maintain the right posterior hepatic arterial flow. Postoperatively, there were no signs of hepatic ischemia. Conclusions When planning PD, including hepatopancreatoduodenectomy, for patients with a tp-CHA, surgeons should simulate various situations for maintaining the hepatic arterial flow. The preservation of the gastric arterial arcade is an option for maintaining the hepatic arterial flow to avoid arterial reconstruction

Comparison of the Diagnostic Efficiency of Radial- and Convex-Arrayed Echoendoscopes for Indirect Findings of Pancreatic Cancer: A Retrospective Comparative Study Using Propensity Score Method

Endoscopic ultrasonography (EUS) is useful for detecting early-stage pancreatic cancer. Because the detection of small lesions is difficult, it is important to detect indirect findings, namely caliber change, retention cysts, and dilatation of the branch duct, during the procedure. Although two types of EUS endoscopes are frequently used, there is no comparative study on their efficacy for detecting indirect findings. Therefore, we aimed to compare the diagnostic efficacy of these two types for indirect findings. We retrospectively analyzed 316 consecutive patients who had undergone EUS for pancreaticobiliary disease at a single center between January 2017 and December 2018. The main outcome was the detection rate of indirect findings and its comparison between the two echoendoscope types. This outcome was achieved using the inverse probability of treatment weighting (IPTW) analysis. The detection rate of indirect findings was higher for the radial-arrayed endoscope than for the convex-arrayed echoendoscope (9.2% vs. 2.3% (p = 0.02)). The univariate analysis also revealed that the radial-arrayed echoendoscope was significantly superior to the convex-arrayed echoendoscope in terms of the detection of indirect findings (odds ratio, 5.94; 95% confidence interval, 1.68–21.10; p = 0.01) after IPTW. After adjustment for magnetic resonance imaging (MRI) and computed tomography (CT), radial-arrayed echoendoscope remained an independent factor for indirect finding detection (odds ratio, 6.04; 95% confidence interval, 1.74–21.00; p = 0.01). Finally, five patients who had indirect EUS findings were diagnosed with pancreatic cancer. Our results indicate that the radial-arrayed echoendoscope is useful for the detection of indirect findings