Mutations in the genes responsible for the synthesis of furan fatty acids resolve the light-induced off-odor in soybean oil.

Soybean oil is the second most produced edible vegetable oil and is used for many edible and industrial materials. Unfortunately, it has the disadvantage of 'reversion flavor' under photooxidative conditions, which produces an off-odor and decreases the quality of edible oil. Reversion flavor and off-odor are caused by minor fatty acids in the triacylglycerol of soybean oil known as furan fatty acids, which produce 3-methyl-2,4-nonanedione (3-MND) upon photooxidation. As a solution to this problem, a reduction in furan fatty acids leads to a decrease in 3-MND, resulting in a reduction in the off-odor induced by light exposure. However, there are no reports on the genes related to the biosynthesis of furan fatty acids in soybean oil. In this study, four mutant lines showing low or no furan fatty acid levels in soybean seeds were isolated from a soybean mutant library. Positional cloning experiments and homology search analysis identified two genes responsible for furan fatty acid biosynthesis in soybean: Glyma.20G201400 and Glyma.04G054100. Ectopic expression of both genes produced furan fatty acids in transgenic soybean hairy roots. The structure of these genes is different from that of the furan fatty acid biosynthetic genes in photosynthetic bacteria. Homologs of these two group of genes are widely conserved in the plant kingdom. The purified oil from the furan fatty acid mutant lines had lower amounts of 3-MND and reduced off-odor after light exposure, compared with oil from the wild-type.

LRRK2 regulates endoplasmic reticulum-mitochondrial tethering through the PERK-mediated ubiquitination pathway.

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common cause of familial Parkinson's disease (PD). Impaired mitochondrial function is suspected to play a major role in PD. Nonetheless, the underlying mechanism by which impaired LRRK2 activity contributes to PD pathology remains unclear. Here, we identified the role of LRRK2 in endoplasmic reticulum (ER)-mitochondrial tethering, which is essential for mitochondrial bioenergetics. LRRK2 regulated the activities of E3 ubiquitin ligases MARCH5, MULAN, and Parkin via kinase-dependent protein-protein interactions. Kinase-active LRRK2(G2019S) dissociated from these ligases, leading to their PERK-mediated phosphorylation and activation, thereby increasing ubiquitin-mediated degradation of ER-mitochondrial tethering proteins. By contrast, kinase-dead LRRK2(D1994A)-bound ligases blocked PERK-mediated phosphorylation and activation of E3 ligases, thereby increasing the levels of ER-mitochondrial tethering proteins. Thus, the role of LRRK2 in the ER-mitochondrial interaction represents an important control point for cell fate and pathogenesis in PD.

Atrial electrical remodeling and function after transcatheter aortic valve replacement in patients with aortic stenosis.

To examine reverse atrial electrical remodeling in patients with aortic stenosis (AS) after trans-catheter aortic valve replacement (TAVR). In 65 consecutive patients with severe AS (83 ± 4 years, 47 (72.3%) females), we analyzed ECG records for the P wave duration (PWD) in lead II and P-terminal force (PTFV1) in V1, and measured cardiac dimensions and function by echocardiography (ECHO) following TAVR. Biomarkers were measured to assess myocardial injury by TAVR. TAVR was successfully performed without major complications: the aortic valve area increased from 0.62 ± 0.14 cm2 to 1.52 ± 0.24cm2, and the trans-aortic pressure gradient decreased from 58.4 ± 15.9 mmHg to 15.0 ± 19.6 mmHg. PWD and PTFV increased immediately after TAVR and returned to the pre-TAVR levels on the next day. Then, the PWD declined toward 6 months after TAVR non-significantly in all patients, but significantly in 25 patients with baseline PWD ≥ 130 ms (P = 0.039). PTFV1 showed no long-term change. Improvement was observed in the ejection fraction, all thickness of the left ventricle and in the left atrial dimensions on ECHO. After recovery from transient aggravation by TAVR procedure, PWD reversed slowly, and the change was significant in those with baseline PWD ≥ 130 ms while change in PTFV1 was not significant at 6 months of follow-up. ECHO showed a reversal of remodeling in the left ventricle and in the left atrial dimension after TAVR.

Blockade of N-Glycosylation Promotes Antitumor Immune Response of T Cells.

Adoptive cellular therapy and its derivative, chimeric AgR T cell therapy, have achieved significant progress against cancer. Major barriers persist, however, including insufficient induction of cytotoxic T cells and exhaustion of tumor-infiltrating lymphocytes. In this study, we discovered a new role for 2-deoxy-d-glucose (2DG) in enhancing the antitumor activity of human T cells against NKG2D ligand-expressing tumor cells. Human T cells treated with 2DG upregulated the NK-specific transcription factors TOX2 and EOMES, thereby acquiring NK cell properties, including high levels of perforin/granzyme and increased sensitivity to IL-2. Notably, rather than inhibiting glycolysis, 2DG modified N-glycosylation, which augmented antitumor activity and cell surface retention of IL-2R of T cells. Moreover, 2DG treatment prevented T cells from binding to galectin-3, a potent tumor Ag associated with T cell anergy. Our results, therefore, suggest that modifying N-glycosylation of T cells with 2DG could improve the efficacy of T cell-based immunotherapies against cancer.

Novel endoscopic ultrasonography classification for assured vertical resection margin (≥500 µm) in colorectal endoscopic submucosal dissection.

BACKGROUND AND AIM: The risk of local recurrence might be low in pT1 colorectal carcinoma with a tumor vertical margin (VM) ≥500 µm. We investigated the relationship between endoscopic ultrasonography (EUS) findings and VM in cases with colorectal endoscopic submucosal dissection (ESD) categorized as Type 2B according to the Japan NBI Expert Team (JNET) classification. METHODS: We analyzed 179 JNET Type 2B colorectal tumors resected by ESD at Hiroshima University Hospital from January 2010 to May 2021. The distance from the tumor invasive front to the muscle layer on EUS was defined as the tumor-free distance (EUS-TFD) and classified as Type I (EUS-TFD ≥1 mm) and II (<1 mm). We investigated the relationship between EUS-TFD and VM and analyzed the predictive factors for VM ≥500 µm. RESULTS: EUS-TFD Type I was diagnosed in 133 (74.3%) lesions: VM ≥500 µm (114, 85.7%); VM <500 µm (19, 14.3%); and VM positive (VM1) (0, 0%). Type II was diagnosed in 46 (25.7%) lesions: VM ≥500 µm (14, 30.5%); VM <500 µm (22, 47.8%); and VM1 (10, 21.7%). In the EUS-TFD Type I cases, 84.5% and 87.8% were protruded and superficial types; whereas for Type II cases, these were 38.9% and 25%, respectively. EUS-TFD classification (Type I), scope operability (good), submucosal invasion depth (<2000 µm), histology at the deepest invasive portion (favorable), and degree of fibrosis (F0/F1) were significant predictors of VM ≥500 µm. CONCLUSIONS: In JNET Type 2B lesions, EUS-TFD classification is a novel diagnostic indicator to predict VM ≥500 µm in ESD preoperatively.

Development of multi-class computer-aided diagnostic systems using the NICE/JNET classifications for colorectal lesions.

BACKGROUND AND AIM: Diagnostic support using artificial intelligence may contribute to the equalization of endoscopic diagnosis of colorectal lesions. We developed computer-aided diagnosis (CADx) support system for diagnosing colorectal lesions using the NBI International Colorectal Endoscopic (NICE) classification and the Japan NBI Expert Team (JNET) classification. METHODS: Using Residual Network as the classifier and NBI images as training images, we developed a CADx based on the NICE classification (CADx-N) and a CADx based on the JNET classification (CADx-J). For validation, 480 non-magnifying and magnifying NBI images were used for the CADx-N and 320 magnifying NBI images were used for the CADx-J. The diagnostic performance of the CADx-N was evaluated using the magnification rate. RESULTS: The accuracy of the CADx-N for Types 1, 2, and 3 was 97.5%, 91.2%, and 93.8%, respectively. The diagnostic performance for each magnification level was good (no statistically significant difference). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the CADx-J were 100%, 96.3%, 82.8%, 100%, and 96.9% for Type 1; 80.3%, 93.7%, 94.1%, 79.2%, and 86.3% for Type 2A; 80.4%, 84.7%, 46.8%, 96.3%, and 84.1% for Type 2B; and 62.5%, 99.6%, 96.8%, 93.8%, and 94.1% for Type 3, respectively. CONCLUSIONS: The multi-class CADx systems had good diagnostic performance with both the NICE and JNET classifications and may aid in educating non-expert endoscopists and assist in diagnosing colorectal lesions.

Vertical tumor margin of endoscopic resection for T1 colorectal carcinoma affects the prognosis of patients undergoing additional surgery.

BACKGROUND: Vertical tumor margin-negative T1 colorectal carcinoma (CRC) is an absolute curative condition following complete endoscopic resection (ER). However, the influence on prognosis in relation to vertical tumor margin is unclear. Therefore, we evaluated the influence of the distance from vertical tumor margin to resected specimen edge (vertical margin distance) of ER for T1b (submucosal invasion depth > 1000 µm) CRC on the prognosis of patients undergoing additional surgery after ER. METHODS: In total, 215 consecutive patients with T1b CRC who underwent additional surgery after ER at Hiroshima University Hospital between February 1992 and June 2019 were enrolled. We assessed 191 patients without lymph node metastases at the additional surgery. The specimens resected by ER were classified into three groups based on the vertical margin distance: patients with a vertical margin distance of ≥ 500 µm (Group A); patients with a vertical margin distance of < 500 µm (Group B); and patients with a positive vertical tumor margin (Group C). Subsequently, we evaluated the prognosis of the patients in relation to the clinicopathological characteristics among the three groups. RESULTS: There were no significant differences in clinicopathological characteristics among the three groups. Group A had a significantly higher recurrence-free 5-year survival rate than Groups B and C (100%, 84.5%, and 81.8%, respectively). Similarly, Group A had a significantly higher disease-specific 5-year survival rate than Group C (100% vs. 95.5%). CONCLUSIONS: Complete en bloc resection with sufficient submucosal layer from the invasive front (vertical margin distance > 500 µm) by ER for T1 CRC reduces the risk of metastatic recurrence after additional surgery.

Indications and outcomes of colorectal hybrid endoscopic submucosal dissection: a large multicenter 10-year study.

BACKGROUND AND AIMS: Hybrid endoscopic submucosal dissection (ESD) is a colorectal lesion resection procedure that includes both planned and salvage procedures. Previous colorectal hybrid ESD studies have involved single institutions or few operators over a short timeframe, and the size for indication has not been established. In this multicentre study, we investigated the clinical outcomes of hybrid ESD for colorectal tumors that met the 30 mm lesion size criterion. METHODS: From January 2008 to December 2018, colorectal hybrid ESD was performed for 172 lesions (diameter range, ≥ 20- < 30 mm) at Hiroshima GI Endoscopy Research Group. We compared clinicopathological characteristics and outcomes between 56 and 116 lesions in planned and salvage groups, respectively. We also compared data between 2008 and 2013 (the first period) and 2014 and 2018 (the second period) to assess operator experience. RESULTS: No significant difference was found in the complete en bloc resection rate between the planned and salvage groups (92.9% vs. 83.6%, respectively). Procedure time was shorter in the planned group (44.5 min) than in the salvage group (72.0 min, p < 0.01). The perforation rate was higher in the salvage group (21.6%) than in the planned group (0%, p < 0.01); however, the perforation rate during snaring in the salvage group was 1.8%. During the second period relative to the first period, we recorded a significantly higher complete en bloc resection rate (95.7% vs. 75.6%, respectively, p < 0.01) and experienced operator rate (75.5% vs. 53.9%, respectively, p < 0.01). Furthermore, no significant difference was found in the complete en bloc resection rate between the planned and salvage groups during the second period (100% vs. 94.4%, respectively). CONCLUSION: Colorectal hybrid ESD, especially salvage hybrid ESD performed by experienced operators, is adoptable and safe for lesions with diameters ranging from ≥ 20 to < 30 mm.

Comparison of the diagnostic performance of NBI, Laser-BLI and LED-BLI: a randomized controlled noninferiority trial.

BACKGROUND AND AIMS: New image-enhanced endoscopy (IEE), blue Light Imaging (LED-BLI) is launched in USA and Europe, whereas Blue Laser Imaging (Laser-BLI) is available only Asian and some countries. No studies have directly compared the diagnostic accuracy of narrow band imaging (NBI), Laser-BLI and LED-BLI for colorectal tumors. The present study aimed to compare the diagnostic accuracy of the three methods for colorectal tumor using the NBI international colorectal endoscopic (NICE) classification and the Japanese NBI Expert Team (JNET) classifications. METHODS: This was a multi-center evaluator-blinded, randomized control trial of patients who underwent endoscopic colorectal tumor resection. The patients were randomly assigned to NBI, Laser-BLI or LED-BLI. Cropped images were sent to blinded external evaluators and diagnosed according to NICE and JNET classifications. The diagnostic accuracy of each endoscopy system was compared with non-inferiority test. RESULTS: A total of 619 colonic tumors were resected from 230 patients and evaluated by external four evaluators. The diagnostic accuracy of NBI for NICE 1, NICE 2, NICE 3 was 90.6%, 90.3% and 99.5%, respectively and for JNET 1, JNET 2A, JNET 2B and JNET 3, it was 94.6%, 72.0%, 79.2% and 99.1%, respectively. In non-inferiority test, Laser-BLI and LED-BLI revealed non-inferiority to NBI in all NICE and JNET categories (p<0.001). CONCLUSIONS: Laser-BLI and LED-BLI had high diagnostic accuracy and non-inferiority of NBI, especially for hyperplastic polyp/sessile serrated lesion and low-grade dysplasia. This is first trial to compare the diagnostic accuracy with NBI, Laser-BLI and LED-BLI and useful to understand the position of each IEE. This trial was registered as UMIN000032107.

[Infectious Thoracic Aortic Aneurysm and Purulent Pericarditis due to Staphylococcus aureus:Report of a Case].

The objective of this case report is to highlight a rare case of infectious thoracic aortic aneurysm and purulent pericarditis simultaneously in a 56-year-old woman. The patient complained of left anterior chest pain and contrast computed tomography (CT) revealed infectious thoracic aortic aneurysm and purulent pericarditis accompanied by massive pericardial effusion. She underwent a pericardial drainage immediately, and antibiotic treatment was initiated. Methicillin-sensitive Staphylococcus aureus was detected in blood and pericardial fluid cultures. On day eight of hospitalization, contrast CT scan showed enlargement of the aortic aneurysm. Therefore, total arch replacement was performed on day 10 using rifampicin-soaked graft. After surgery, antibiotic treatment was continued, till inflammatory markers became negative. She was discharged on day 66 without developing anastomotic pseudoaneurysms nor constrictive pericarditis.

Long-term prognosis after endoscopic submucosal dissection for colorectal tumors in patients aged over 80 years.

BACKGROUND: In Japan, endoscopic submucosal dissection (ESD) is standardized for large colorectal tumors. However, its validity in the elderly population is unclear. We aimed to evaluate the safety and efficacy of ESD for colorectal tumors in elderly patients aged over 80 years. METHODS: ESD was performed on 178 tumors in 165 consecutive patients aged over 80 years between December 2008 and December 2018. We retrospectively evaluated the clinicopathological characteristics and clinical outcomes of ESD. We also assessed the prognosis of 160 patients followed up for more than 12 months. RESULTS: The mean patient age was 83.7 ± 3.1 years. The number of patients with comorbidities was 100 (62.5%). Among all patients, 106 (64.2%) were categorized as class 1 or 2 according to the American Society of Anesthesiologists classification of physical status (ASA-PS), and 59 (35.8%) were classified as class 3. The mean procedure time was 97.7 ± 79.3 min. The rate of histological en bloc resection was 93.8% (167/178). Delayed bleeding in 11 cases (6.2%) and perforation in 7 cases (3.9%) were treated conservatively. The 5-year survival rate was 89.9%. No deaths from primary disease (mean follow-up time: 35.3 ± 27.5 months) were observed. Overall survival rates were significantly lower in the non-curative resection group that did not undergo additional surgery than in the curative resection group (P = 0.0152) and non-curative group that underwent additional surgery (P = 0.0259). Overall survival rates were higher for ASA-PS class 1 or 2 patients than class 3 patients (P = 0.0105). Metachronous tumors (> 5 mm) developed in 9.4% of patients. CONCLUSIONS: ESD for colorectal tumors in patients aged over 80 years is safe. Colorectal cancer-associated deaths were prevented although comorbidities pose a high risk of poor prognosis.

Effect of educational lecture on the diagnostic accuracy of Japan NBI Expert Team classification for colorectal lesions.

BACKGROUND: An educational and training program is required for generalization of Japan NBI Expert Team (JNET) classification. However, there is no detailed report on the learning curve of the diagnostic accuracy of endoscopists using JNET classification. We examined the effect of an educational lecture on beginners and less experienced endoscopists for improving their diagnostic accuracy of colorectal lesions by JNET classification. METHODS: Seven beginners with no endoscopy experience (NEE group), 7 less experienced endoscopists (LEE group), and 3 highly experienced endoscopists (HEE group) performed diagnosis using JNET classification for randomized NBI images of colorectal lesions from 180 cases (Type 1: 22 cases, Type 2A: 105 cases, Type 2B: 33 cases, and Type 3: 20 cases). Next, the NEE and LEE groups received a lecture on JNET classification, and all 3 groups repeated the diagnostic process. We compared the correct diagnosis rate and interobserver agreement before and after the lecture comprehensively and for each JNET type. RESULTS: In the HEE group, the correct diagnosis rate was more than 90% with good interobserver agreements (kappa value: 0.78-0.85). In the NEE and LEE groups, the correct diagnosis rate (NEE: 60.2 → 68.0%, P < 0.01; LEE: 66.4 → 86.7%, P < 0.01), high-confidence correct diagnosis rate (NEE: 19.6 → 37.2%, P < 0.01; LEE: 43.6 → 61.1%, P < 0.01), and interobserver agreement (kappa value, NEE: 0.32 → 0.43; LEE: 0.39 → 0.75) improved after the lecture. In the examination by each JNET type, the specificity and positive predictive value in the NEE and LEE groups generally improved after the lecture. CONCLUSION: After conducting an appropriate lecture, the diagnostic ability using JNET classification was improved in beginners or endoscopists with less experience in NBI magnifying endoscopy.

Clinical usefulness of linked color imaging for evaluation of endoscopic activity and prediction of relapse in ulcerative colitis.

PURPOSE: In the treatment of ulcerative colitis (UC), accurate evaluation of UC activity is important to achieve mucosal healing. We sought to investigate the clinical utility of linked color imaging (LCI) for the evaluation of endoscopic activity and prediction of relapse in UC patients. METHODS: We enrolled 72 consecutive UC patients in remission who underwent colonoscopy at our institution between September 2016 and October 2018. The relationship between the presence of redness in white light imaging (WLI) and LCI and histopathological inflammation (Geboes score: GS) at 238 biopsy sites was examined. We also assessed the presence or absence of planar redness in the entire rectum as ± and classified the patients into three groups according to the combination of WLI/LCI: A: WLI-/LCI-, B: WLI-/LCI+, and C: WLI+/LCI+. The relationship between WLI/LCI classification and relapse in 64 patients followed up for more than 12 months from initial colonoscopy was assessed and compared to the Mayo endoscopic subscore (MES). RESULTS: A GS of 0 or 1 accounted for 89% of WLI/LCI non-redness sites, while a GS of 2 or 3 accounted for 42% of WLI non-redness/LCI redness sites. LCI findings were significantly correlated with GS. During follow-up, 10 patients in group C and four patients in group B relapsed, but none in group A. Non-relapse rates were significantly correlated with WLI/LCI classification, but not with MES. CONCLUSION: LCI is a useful modality for accurate assessment of endoscopic activity and prediction of relapse in UC by detecting mild inflammation unrecognizable by WLI.

Gastric Adenoma: A High Incidence Rate of Developing Carcinoma and Risk of Metachronous Gastric Cancer according to Long-Term Follow-Up.

INTRODUCTION: Gastric adenomas are histologically defined as benign epithelial tumors. While some of them remain adenomas for a long time, others progress to carcinomas. However, long-term outcomes of such cases are not entirely clear. Here, we explored the risk factors and incidence of developing carcinoma from gastric adenoma as well as metachronous gastric cancer. METHODS: This study was conducted at a facility that adopted a follow-up strategy for gastric adenoma. Lesions histologically diagnosed as gastric intestinal-type adenomas between January 2004 and December 2016 were analyzed. Clinicopathological data were collected from patients' medical records, and histological changes from adenoma to carcinoma during endoscopic follow-up and risk factors of cancer development were evaluated. RESULTS: This study involved 409 lesions from 376 patients. The analysis of the development of gastric cancer from adenoma and metachronous gastric cancer was ultimately performed for 282 lesions from 258 patients and 269 lesions from 246 patients, respectively, due to different follow-up periods. The 5-year rate of carcinoma development was 34.0%. Risk factors for carcinoma development upon multivariate analysis were lesion size ≥15 mm and morphological depression. All cases with both factors developed gastric carcinoma, and 50.5% of those with either factor developed carcinoma within 5 years. Gastric adenoma was accompanied by metachronous gastric cancer in 1.5% of the patients annually. The only risk factor for metachronous gastric carcinoma was primary adenoma progressing to carcinoma during the follow-up period. DISCUSSION/CONCLUSION: Given the high rate of carcinoma development in patients with risk factors, resection of gastric adenoma should be considered during the initial examination. Careful observation and follow-up should also be conducted to detect not only changes in the primary adenoma but also the occurrence of metachronous carcinoma, especially in cases of adenoma progressing to carcinoma.

Tolerability and efficacy of the concentration of iodine solution during esophageal chromoendoscopy: a double-blind randomized controlled trial.

BACKGROUND AND AIMS: Esophageal chromoendoscopy with iodine solution is an important diagnostic method for the detection of superficial esophageal cancer. However, the concentration of iodine solution has differed among reports. This study aimed to evaluate patient discomfort with different iodine concentrations. METHODS: We performed a prospective, double-blind, randomized study. We prospectively enrolled and analyzed 77 patients who were at high risk for esophageal carcinoma and scheduled to undergo EGD from March 2018 to January 2019. All patients were divided into 2 groups before the procedure to compare pain measurements: a 1% iodine solution group (group A) and a 2% iodine solution group (group B). The primary endpoint of this study was the difference in pain measurement between 1% and 2% iodine solution chromoendoscopy. Secondary endpoints were safety, detection yield, and color evaluation based on both the endoscopist's survey and color values, as determined using the Commission Internationale de l'Eclairage (CIELAB, Vienna, Austria) color evaluation system, in the iodine-faded and iodine-stained area of each group. RESULTS: Heartburn and retrosternal pain in group A were significantly lower than those in group B (P = .02). Eleven patients reported heartburn and retrosternal pain (group A, 2; group B, 9). Four patients reported pain above the sternal angle and 7 below the sternal angle. There was no significant difference between the 2 groups with regard to detection yield, color evaluation by the endoscopist's assessment, or color values. No patients had any adverse events, and all safely completed this study. CONCLUSIONS: The 2% iodine solution resulted in significantly greater pain than the 1% iodine solution, and the color of the stained esophageal images of each group was the same from this study. Therefore, the 1% iodine solution is recommended for esophageal chromoendoscopy. (Clinical trial registration number: UMIN 000029796.).

Protective effects of cilengitide on inflammation in chondrocytes under excessive mechanical stress.

Chondrocytes constantly receive external stimuli, which regulates remodeling. An optimal level of mechanical stress is essential for maintaining chondrocyte homeostasis, however, excessive mechanical stress induces inflammatory cytokines and protease, such as matrix metalloproteinases (MMPs). Therefore, excessive mechanical stress is considered to be one of the main causes to cartilage destruction leading to osteoarthritis (OA). Integrins are well-known as cell adhesion molecules and act as receptors for extracellular matrix (ECM), and are believed to control intracellular signaling pathways both physically and chemically as a mechanoreceptor. However, few studies have focused on the roles and functions of integrins in inflammation caused by excessive mechanical stress. In this study, we examined the relationship between integrins (αVß3 and αVß5) and the expression of inflammatory factors under mechanical loading in chondrocytes by using an integrin receptor antagonist (cilengitide). Cilengitide suppressed the gene expression of interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), matrix metalloproteinase-3 (MMP-3), and MMP-13 induced by excessive mechanical stress. In addition, the protein expression of IL1-ß and MMP-13 was also inhibited by the addition of cilengitide. Next, we investigated the involvement of intracellular signaling pathways in stress-induced integrin signaling in chondrocytes by using western blotting. The levels of p-FAK, p-ERK, p-JNK, and p-p38 were enhanced by excessive mechanical stress and the enhancement was suppressed by treatment with cilengitide. In conclusion, this study revealed that excessive mechanical stress may activate integrins αVß3 and αVß5 on the surface of chondrocytes and thereby induce an inflammatory reaction by upregulating the expression of IL-1ß, TNF-α, MMP-3, and MMP-13 through phosphorylation of FAK and MAPKs.

Evaluation of the Usefulness and Convenience of the Kyoto Classification of Gastritis in the Endoscopic Diagnosis of the Helicobacter pylori Infection Status.

BACKGROUND/AIMS: The Kyoto Classification of Gastritis was published in 2014. Although this classification is now widely used in Japan, its usefulness and convenience have not been sufficiently evaluated. This study aimed to evaluate the usefulness and convenience of this classification in the endoscopic diagnosis of Helicobacter pylori infection. METHODS: We made a test for the endoscopic diagnosis of H. pylori infection comprising 30 cases who had representative endoscopic features of non-, active, or inactive gastritis. Thirty-eight participants took the test before and after a brief mini-lecture on the Kyoto Classification of Gastritis. Eighteen participants took the test again 3 months later. We investigated the accuracy before, just after, and 3 months after the mini-lecture. RESULTS: The accuracy of endoscopists after the lecture was significantly improved in comparison to before the lecture (77.6 vs. 83.3%). Medical students also showed significantly improved accuracy after the lecture (56.7 vs. 71.7%). Among endoscopists, this improvement was maintained after 3 months. Before the lecture, the accuracy of diagnosing non-gastritis was 90.3%; it tended to be further improved 3 months later (96.5%). A >10% point increase was observed in diagnosing active (72.7-83.3%) and inactive gastritis (73.2-84.3%) at 3 months after the lecture in comparison to before the lecture. CONCLUSION: A brief mini-lecture on the Kyoto Classification of Gastritis improved the accuracy in the endoscopic diagnosis of gastritis, indicating that understanding this classification is useful for the prompt diagnosis of H. pylori infection during esophagogastroduodenoscopy.

Geochemical speciation of metals (Cu, Pb, Cd) in fishpond sediments in Batan Bay, Aklan, Philippines.

Batan Bay in Aklan, Philippines supports a population largely dependent on coastal fisheries. The development of aquaculture technologies coupled with over-crowded fish pens has negatively affected its natural dynamics and environmental quality. Land-use activities including ports and shipyard further aggravate the problem by contributing to chemical pollution. The present study applied sequential extraction techniques to determine the geochemical speciation of metals in fishpond sediments. Samples were processed and analyzed for Cu, Cd, and Pb using flame atomic absorption spectroscopy. Copper (Cu) showed the highest concentration (10.61-66.81 µg/g-dry weight of sediment). Lead (Pb) content ranged from below detection limit to 15.14 µg/g, while Cd concentration ranged from below detection limit to 2.50 µg/g. Fractionation study showed that the Cu present in the fishpond sediments is mostly non-residual (50.03-73.34%) and significantly associated with the oxidizable fraction (33.89-64.75%). In contrast, the residual fraction served as the dominant host of Pb (33.55-62.68%) in the sediments. Comparison of the results with US EPA and NOAA sediment quality guidelines also revealed that the Batan Bay sediments may be considered generally non-polluted with respect Cu, Pb, and Cd, and not expected to cause adverse effects to aquatic organisms under normal conditions. However, under certain redox conditions, most of the sites may be considered moderately polluted as a result of Cu mobilization from the non-residual fractions of the sediments. Overall, geochemical speciation studies in an important fishery area like Batan Bay will provide valuable insights into the availability of metal contaminants to aquatic organisms under certain environmental conditions.

Semaphorin 3A Inhibits Inflammation in Chondrocytes under Excessive Mechanical Stress.

BACKGROUND: Excessive mechanical stress causes inflammation and destruction of cartilage and is considered one of the cause of osteoarthritis (OA). Expression of semaphorin 3A (Sema3A), which is an axon guidance molecule, has been confirmed in chondrocytes. However, there are few reports about Sema3A in chondrocytes, and the effects of Sema3A on inflammation in the cartilage are poorly understood. The aim of this study was to examine the role of Sema3A in inflammation caused by high magnitude cyclic tensile strain (CTS). METHODS: Expression of Sema3A and its receptors neuropilin-1 (NRP-1) and plexin-A1 (PLXA1) in ATDC5 cells was examined by Western blot analysis. ATDC5 cells were subjected to CTS of 0.5 Hz, 10% elongation with added Sema3A for 3 h. Gene expression of IL-1ß, TNF-ɑ, COX-2, MMP-3, and MMP-13 was examined by qPCR analysis. Furthermore, the phosphorylation of AKT, ERK, and NF-κB was detected by Western blot analysis. RESULTS: Added Sema3A inhibited the gene expression of inflammatory cytokines upregulated by CTS in a dose-dependent manner. Addition of Sema3A suppressed the activation of AKT, ERK, and NF-κB in a dose-dependent manner. CONCLUSIONS: Sema3A reduces the gene expression of inflammatory cytokines by downregulating the activation of AKT, ERK, and NF-κB pathways in ATDC5 cells under CTS.