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Metalloproteinases were first identified as collagen cleaving enzymes and are now appreciated to play important roles in a wide variety of biological processes. The aberrant activity and dysregulation of the metalloproteinase family are linked to numerous diseases including cardiovascular and pulmonary diseases, chronic wounds, cancer, fibrosis and arthritis. Osteoarthritis (OA) is the most prevalent age-related joint disorder that causes pain and disability, but there are no disease-modifying drugs available. The hallmark of OA is loss of articular cartilage and elevated activities of matrix-degrading metalloproteinases are responsible. These enzymes do not exist in isolation and their activity is tightly regulated by a number of processes, such as transcription, proteolytic activation, interaction with their inhibitors, cell surface and extracellular matrix molecules, and endocytic clearance from the extracellular milieu. Here, we describe the functions and roles of metalloproteinase family in OA pathogenesis. We highlight recent studies that have illustrated novel mechanisms regulating their extracellular activity and impairment of such regulations that lead to the development of OA. We also discuss how to stop or slow down the degenerative processes by targeting aberrant metalloproteinase activity, which may in future become therapeutic interventions for the disease.

Background Treatment of fusiform vertebral artery aneurysms is demanding because meticulous preservation of perforators and the PICA is required. Methods The occipital artery is mapped with Doppler and harvested by incising the overlying muscle, allowing en-bloc elevation of the musculature. Accurate burr-hole placement minimizes venous sinus injury and reduces the bony defect, while early opening of the foramen magnum improves anatomical orientation and facilitates the bypass technique. The extracranial vertebral artery is safely identified with Doppler before performing OA–PICA bypass and subsequent trapping. Conclusion Standardized steps improve technical reliability and enhance clinical outcomes.

Currently, a power-to-gas technology that obtains electrolytic hydrogen from renewable energy sources, synthesizes it with carbon dioxide, and converts it to methane has received a great deal of attention. It is called methanation, but there are few studies examining alternative substances to replace the raw material of hydrogen. Since hydrogen does not exist naturally, it is important to find other substances that react with carbon dioxide. We focus on flammable gases formed in oil refineries and petrochemical plants. In this study, based on chemical equilibrium calculations of the so-called NASA-CEA, we tested several gases including flammable and nonflammable gases by reacting them with carbon dioxide. Some of them are included in flare stacks. The reactants in the present gas conversion were H2O, CH3OH, C2H5OH, NH3, CH3CN, CH3N2CH3, C3H8O (1-propanol), C3H8O (2-propanol), C2H6, C2H4, C3H8, C3H6, C3H4 (allene), C3H4 (propine), C6H5OH, (CH3COOH)2, HCOOH, HF, HCl, HBr, H2S, HNO3, and SiH4. The results show that substances with more hydrogen atoms per mol of reactant, such as C3H8, CH3N2CH3, and SiH4, can produce more synthetic methane. One more finding is that graphite due to coking increases proportionately to the number of carbon atoms in the chemical formula.

The optimal procedural protocol for coronary stent deployment remains undetermined. Post-dilation with a high-pressure balloon is often performed to optimize the stent expansion. However, high-pressure dilation also carries the potential risk of coronary artery injury. A previous in vitro study reported that multiple-times balloon inflation at the same pressure resulted in better stent expansion compared to one-time balloon inflation. In our facility, we frequently perform the repeated 3-time-balloon-inflation method, wherein the stent delivery balloon was inflated 3 times at nominal pressure to deploy the stent, to improve stent expansion without high-pressure balloon inflation. Although this method seems effective in avoiding excessive high-pressure dilation, its clinical data are insufficient. In this study, we investigated the clinical outcomes of the repeated 3-time-balloon-inflation method. This retrospective study included 370 patients with 467 stented coronary lesions. These subjects were divided into two groups: one with standard balloon inflation and the other with repeated 3-time balloon inflation, and treatment outcomes were compared. The repeated 3-time-balloon-inflation group had 254 lesions, and the standard-balloon-inflation group had 213 lesions. Stent edge dissection occurred in 6 lesions (2.8%) in the standard-balloon-inflation group, whereas did not occur in the repeated 3-time-balloon-inflation group. A statistically significant difference remained even after propensity score matching ( p  = 0.040). The final minimum stent area and long-term clinical outcomes were not significantly different between the two groups. The repeated 3-time-balloon-inflation method may reduce stent edge dissection while demonstrating comparable minimal stent area and long-term outcomes to the standard-balloon-inflation method.

To evaluate whether reduced field-of-view (rFOV) DWI sequence improves the differentiation between non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) using VI-RADS. Eighty-nine patients underwent bladder MRI with full field-of-view (fFOV) DWI and rFOV DWI sequence. Images were independently evaluated by 2 radiologists. The sensitivities, specificities, accuracies, and areas under the curve (AUCs) for the differentiation between NMIBC and MIBC with fFOV DWI and with rFOV DWI sequence were calculated using VI-RADS. Apparent diffusion coefficients (ADC) values were measured for each patient and averaged. The sensitivity, specificity, accuracy, and AUC by reader 1 were 92%, 78%, 82% and 0.905 with fFOV DWI, and 92%, 86%, 88% and 0.916 with rFOV DWI sequence, respectively. The sensitivity, specificity, accuracy and AUC by reader 2 were 96%, 76%, 82% and 0.900 with conventional DWI, and 96%, 81%, 85% and 0.907 with rFOV DWI sequence, respectively. The specificity and accuracy of reader 1 were significantly better with rFOV DWI sequence than with fFOV DWI, in contrast there was no significant difference for the others. The average of ADC values of fFOV DWI and rFOV DWI sequence were 1.004×10-6 mm2/s and 1.003×10-6 mm2/s, respectively. The diagnostic ability of rFOV DWI sequence may be better than that of fFOV DWI using VI-RADS for the differentiation between NMIBC and MIBC regardless of image-reading experience, it is controversial.

Backgrounds Stent migration following endoscopic ultrasonography-guided hepaticogastrostomy (EUS-HGS) may sometimes be fatal because there are no adhesions between the biliary tract and stomach. To prevent stent migration and minimize the stent length in the abdominal cavity, we recently performed EUS-HGS using the technique of releasing the stent within the scope channel. Aims To examine the technical feasibility of the intra-scope channel stent release technique. Methods Forty-one consecutive patients who underwent EUS-HGS were enrolled. Between October 2015 and December 2015, EUS-HGS was performed using the extra-scope channel release technique, while the intra-scope channel release technique was performed between January 2016 and March 2016. Results The distance between the hepatic parenchyma and the stomach wall after EUS-HGS in the intra-scope channel stent release group was significantly shorter than that in the extra-scope channel release group (0.66 ± 1.25 vs 2.52 ± 0.97, P  < 0.05). Adverse events, such as biloma or stent migration, were seen in only the extra-scope channel release group. Conclusion In conclusion, although additional cases and randomized controlled studies using metal stents of various lengths are needed, our technique is likely to be clinically useful for the prevention of early and late stent migration.

Inhalation studies are the gold standard for the estimation of the harmful effects of respirable chemical substances, while there is limited evidence of the harmful effects of chemical substances by intratracheal instillation. We reviewed the effectiveness of intratracheal instillation studies for estimating the hazards of nanoparticles, mainly using papers in which both inhalation and intratracheal instillation studies were performed using the same nanoparticles. Compared to inhalation studies, there is a tendency in intratracheal instillation studies that pulmonary inflammation lasted longer in the lungs. A difference in pulmonary inflammation between high and low toxicity nanoparticles was observed in the intratracheal instillation studies, as in the inhalation studies. Among the endpoints of pulmonary toxicity, the kinetics of neutrophil counts, percentage of neutrophils, and chemokines for neutrophils and macrophages, heme oxygenase-1 (HO-1) in bronchoalveolar lavage fluid (BALF), reflected pulmonary inflammation, suggesting that these markers may be considered the predictive markers of pulmonary toxicity in both types of study. When comparing pulmonary inflammation between intratracheal instillation and inhalation studies under the same initial lung burden, there is a tendency that the inflammatory response following the intratracheal instillation of nanoparticles is greater than or equal to that following the inhalation of nanoparticles. If the difference in clearance in both studies is not large, the estimations of pulmonary toxicity are close. We suggest that intratracheal instillation studies can be useful for ranking the hazard of nanoparticles through pulmonary inflammation.

BackgroundIn Japan, the prevalence of constipation-predominant irritable bowel syndrome (IBS-C) and functional constipation (FC) diagnosed by the Rome III criteria is unclear, as are the demographic profile, quality of life (QOL), and habits of persons with IBS-C or FC.MethodsWe performed an internet survey of constipation. After extracting 3000 persons fitting the composition of the general Japanese population, we investigated demographic factors, lifestyle, defecation, and laxatives. IBS-C and FC were diagnosed by Rome III criteria. Respondents also completed the Japanese IBS severity index (IBS-SI-J), Japanese IBS QOL scale (IBS-QOL-J), SF-8, Hospital Anxiety and Depression Scale (HADS), and Japanese Health Practice Index (JHPI).ResultsThere were 262 respondents with FC (8.73%) [73 men and 189 women; mean age: 49.8 ± 13.1 years; mean body mass index (BMI): 21.0 ± 3.3 g/m2] and 149 respondents with IBS-C (4.97%) (76 men and 73 women; mean age; 41.6 ± 13.7 years; mean BMI: 20.8 ± 3.0 kg/m2). Total IBS-QOL-J score were significantly lower in the IBS-C group than the FC group. With regard to SF-8, score of mental component summary (MCS) was significantly lower in the IBS-C group. The total IBS-SI-J score and item scores, except for satisfactory defecation, were significantly higher in the IBS-C group than the FC group. HADS showed a significant increase of anxiety and depression in both the groups, and the JHPI revealed insufficient sleep.ConclusionsIn Japan, among the population of under 70 years old, the prevalence of IBS-C and FC (Rome III criteria) was 4.97% and 8.76%, respectively. IBS-C caused more severe symptoms than FC, resulting in impairment of QOL.

Background/Aim: Mammalian target of rapamycin (mTOR) inhibitors represent the standard of care for metastatic renal cell carcinoma (RCC). However, treatment outcomes are relatively poor, suggesting a potential problem with tolerating mTOR inhibitors. The aim of this study was to establish everolimus-resistant sublines and to compare their molecular characteristics with those of their counterparts. Materials and Methods: Human-derived RCC, Caki-2, and 786-O cells were continuously exposed to everolimus at 1 μM, and the established resistant sublines were designated as Caki/EV and 786/EV, respectively. Cellular characteristics were compared between both cells. Results: Caki/EV and 786/EV cells showed a decrease in sensitivity to everolimus as well as other mTOR inhibitors. Expression of mTOR and its effectors exhibited no alteration in resistant sublines and their counterparts. However, phosphorylation of S6K, an index of mTOR activity, decreased in resistant sublines. PCR array analysis of mTOR signaling pathway-related factors indicated that the expression of INSR, TP53, and IGFBP3 increased in Caki/EV cells, whereas that of TELO2, HRAS, and SGK1 was up-regulated in 786/EV cells. The levels of DDIT4, DEPTOR, HIF1A, and PLD1 mRNAs decreased in both cell lines. Conclusion: The novel everolimus-resistant Caki/EV and 786/EV cells exhibited cross-resistance to other mTOR inhibitors and decreased mTOR activity. Furthermore, down-regulation of DDIT4, DEPTOR, HIF1A, and PLD1 may contribute to everolimus resistance.

The appearances of Schisandrae Sphenantherae Fructus (SSF) and Schisandrae Chinensis Fructus (SCF) are very similar. Thus, being able to distinguish between SSF and SCF is useful for the quality control of these herbal medicines. In this study, two kinds of electrochemical fingerprint analyses using voltammetry or HPLC with electrochemical detection (HPLC-ECD) were developed in combination with multivariate analysis for discriminating between SSF and SCF. The data sets of the oxidation current values from voltammograms of SSF and SCF samples ranging from +0.5 to +1.0 V were applied to perform a partial least squares discriminant analysis (PLS-DA). Moreover, the data sets of the current heights of the characteristic target peaks on the chromatograms at an applied potential of +0.9 V were also applied to perform PLS-DA. In each PLS-DA obtained from the voltammograms and chromatograms, the scores for the SSF samples were plotted on a different region compared with the scores for the SCF samples. Considering the results of the cross-validation, the HPLC-ECD clearly discriminated between the SSF and SCF samples when compared with the voltammetry. In conclusion, our results show that the present electrochemical fingerprint analyses coupled with PLS-DA are useful as a means for discriminating between the SSF and SCF samples.