The relationship between observation interval and prognosis in pancreatic cancer concomitant with intraductal papillary mucinous neoplasia.

BACKGROUND: Intraductal papillary mucinous neoplasia (IPMN) is a risk factor for pancreatic cancer (PC). PC concomitant with IPMN shows rapid progression similar to de novo PC, therefore, the appropriate observation interval (OI) is not yet clear. PATIENTS AND METHOD: This was a multicenter retrospective observational study, and patients with PC concomitant with IPMN were analyzed. OI was defined as the interval between the date of imaging at PC diagnosis and just before the diagnosis. Clinical factors of PC and prognosis were assessed according to OI. RESULTS: From January 2010 to December 2018, 73 patients from 11 institutions were enrolled. The images performed just before PC diagnosis were contrast-enhanced CT/magnetic resonance imaging/endoscopic ultrasonography in 44/27/2 patients, respectively. The median cyst size was 14.0 mm, and the median main pancreatic duct diameter was 3.0 mm. The median OI was 6.8 months. In OI 6 months or less (OI ≤ 6 M)/OI more than 6 months (OI > 6 M), the mean tumor size, the frequencies of metastatic PC, resectable PC and early-stage PC were 20.1/21.5 mm (P = 0.91), 12.1 %/32.5 % (P = 0.05), 72.7 %/52.5 % (P = 0.09) and 27.3 %/25.0 % (P = 1.00), respectively. The median overall survival was 35.5 months in OI ≤ 6 M and 16.2 months in OI > 6 M (P = 0.05). CONCLUSION: In OI 6 months or less, the rate of resectable PC was high, however, the rate of early PC was almost the same as that of OI more than 6 months. Approximately 10 % of cases found in the advanced stage with metastasis even if OI 6 months or less.

Adverse events of self-expandable metal stent placement for malignant distal biliary obstruction: a large multicenter study.

BACKGROUND AND AIMS: Endoscopic placement of self-expandable metal stents (SEMSs) for malignant distal biliary obstruction (MDBO) may be accompanied by several types of adverse events. The present study analyzed the adverse events occurring after SEMS placement for MDBO. METHODS: The present study retrospectively investigated the incidence and types of adverse events in patients who underwent SEMS placement for MDBO between April 2018 and March 2021 at 26 hospitals. Risk factors for acute pancreatitis, cholecystitis, and recurrent biliary obstruction (RBO) were evaluated by univariate and multivariate analyses. RESULTS: Of the 1425 patients implanted with SEMSs for MDBO, 228 (16.0%) and 393 (27.6%) experienced early adverse events and RBO, respectively. Pancreatic duct without tumor involvement (P = .023), intact papilla (P = .025), and SEMS placement across the papilla (P = .037) were independent risk factors for acute pancreatitis. Tumor involvement in the orifice of the cystic duct was an independent risk factor for cholecystitis (P < .001). Use of fully and partially covered SEMSs was an independent risk factor for food impaction and/or sludge. Use of fully covered SEMSs was an independent risk factor for stent migration. Use of uncovered SEMSs and laser-cut SEMSs was an independent risk factor for tumor ingrowth. CONCLUSIONS: Pancreatic duct without tumor involvement, intact papilla, and SEMS placement across the papilla were independent risk factors for acute pancreatitis, and tumor involvement in the orifice of the cystic duct was an independent risk factor for cholecystitis. The risk factors for food impaction and/or sludge, stent migration, and tumor ingrowth differed among types of SEMSs.

Impact of time from diagnosis to chemotherapy on prognosis in advanced pancreatic cancer.

BACKGROUND: Due to the aggressive nature and poor prognosis of advanced pancreatic cancer, prompt initiation of treatment is critical. We investigated the effect of the interval between cancer diagnosis and initiation of chemotherapy on survival in patients with advanced pancreatic cancer. METHODS: In this retrospective, single-centre study, consecutive patients with advanced pancreatic cancer between April 2013 and March 2022 were analyzed. Data were extracted from the electronic medical records of patients who received chemotherapy for metastatic, locally advanced or resectable pancreatic cancer or who received chemotherapy due to either being intolerant of or declining surgery. We compared overall survival between two groups: the early waiting time group (waiting time ≤30 days from diagnosis to chemotherapy initiation) and the elective waiting time group (waiting time ≥31 days). Prognostic factors, including biliary drainage, were considered. The impact of waiting time on survival was assessed by univariate and multivariate analyses with Cox proportional hazard models. A 1:1 propensity score matching approach was used to balance bias, accounting for significant poor prognosis factors, age and sex. RESULTS: The study involved 137 patients. Overall survival exhibited no statistically significant difference between the early and elective waiting time groups (207 and 261 days, P = 0.2518). Univariate and multivariate analyses identified poor performance status and metastasis presence as predictors of worse prognosis. This finding persisted post propensity score matching (275 and 222 days, P = 0.8223). CONCLUSIONS: Our study revealed that initiating chemotherapy ˃30 days later does not significantly affect treatment efficacy compared to within 30 days of diagnosis.

Impact of Initial Body Weight Loss on Prognosis in Advanced Pancreatic Cancer: Insights From a Single-Center Retrospective Study.

BACKGROUND: Pancreatic cancer (PC) has a poor prognosis, with body weight loss commonly observed at diagnosis. However, the impact on PC prognosis of weight loss at the time of diagnosis on PC prognosis is unknown. METHODS: This retrospective, single-center study enrolled consecutively patients diagnosed with metastatic or locally advanced PC or resectable PC who were intolerant of or refused surgery. Patients who had lost more than 5% of their body weight or more than 2% and had a body mass index (BMI) of less than 20 kg/m2 at diagnosis were classified as experiencing body weight loss. Patients were subclassified into 2 groups: patients with and without weight loss. The study evaluated patient-related and PC-related factors affecting prognosis. Cox proportional hazards models were used to assess factors affecting prognosis. The primary endpoint was overall survival. Additionally, 1:1 propensity score matching was performed to reduce bias. RESULTS: In total, 220 patients were included in the study. The median age of the patients was 74 years, and 49.1% were male. Weight loss at diagnosis was observed in 43.2% of patients. There were no significant differences in clinical factors, except for anthropometric parameters, between the groups. The median survival time did not differ between the weight loss and no weight loss groups (149 and 173 days, respectively, P = .669). After matching, no significant differences in survival times were observed between the 2 groups. CONCLUSIONS: This study found no association between weight loss at diagnosis and prognosis in patients with advanced PC treated with best supportive care or chemotherapy.

Gastrointestinal symptoms in 609 Japanese patients with COVID-19: a single-center retrospective study.

BACKGROUND: GI symptoms are common in acute COVID-19 patients. This study aimed to characterize the GI symptoms occurring in Japanese COVID-19 patients. METHODS: This retrospective single-center cohort study included 751 hospitalized acute COVID-19 patients. The primary outcomes were the frequency and severity of GI symptoms. The secondary outcomes included the association between COVID-19 severity and GI symptoms and the timing of GI symptom onset. RESULTS: After exclusion, the data of 609 patients were analyzed. The median age was 62 years, and 55% were male. The median time from initial symptom onset to admission was five days. On admission, 92% of the patients had fever, 35.1% had fatigue, 75% had respiratory symptoms, and 75% had pneumonia. The sample included patients with mild (19%), moderate (59%), and severe COVID-19 (22%). A total of 218 patients (36%) had GI symptoms, of which 93% were classified as grade 1/2; 170 patients had both respiratory and GI symptoms. Diarrhea was the most frequent GI symptom, occurring in 170 patients, followed by anorexia in 73 patients and nausea/vomiting in 36 patients, and abdominal pain in 8 patients. There was no significant relationship between COVID-19 severity and GI symptoms. Among COVID-19 patients with both GI and respiratory symptoms, 48% had respiratory symptoms preceding GI symptoms, 25% had GI symptoms preceding respiratory symptoms and 27% had a simultaneous onset of respiratory and GI symptoms. CONCLUSION: Thirty-six percent of the Japanese COVID-19 patients had GI symptoms; diarrhea was the most frequent GI symptom but did not predict severe COVID-19.

Stratification Based on Risk Factors at Diagnosis Could Predict Progression in Patients with Pancreatic Cysts.

BACKGROUND: Predicting the risk of malignant transformation in pancreatic cyst patients is challenging. AIM: We retrospectively investigated the risk factors for malignant transformation in pancreatic cyst patients. METHODS: Patients with pancreatic cysts diagnosed using imaging tests were followed from November 2008 to December 2021. A significant change was defined as the additional development of high-risk stigmata (HRS), worrisome features (WFs), or pancreatic cancer during monitoring. RESULTS: In total, 479 patients were analyzed, with a median observation period of 50 months. Forty-four patients (9.2%) showed significant changes, and eight (1.7%) developed pancreatic cancer. The univariate analysis showed that the cyst diameter at diagnosis (≥ 14 mm), main pancreatic duct (MPD) diameter at diagnosis (≥ 3 mm), presence of multilocular cysts, and an inconsistent MPD caliber were significant predictive factors for a significant change. One point was assigned for each significant factor. We grouped the patients into three groups: the low-risk group (total score 0), medium-risk group (score 1-2), and high-risk group (score 3-4). The high-risk group had a higher risk of a significant change than the medium- and low-risk groups (age-adjusted HRs for the medium-risk and high-risk groups were 3.0 and 5.2 compared with the low-risk group). CONCLUSION: Stratification based on risk factors may help predict the development of significant changes in pancreatic cyst patients.

Predictive factors of collateral vessel development induced by oxaliplatin-based chemotherapy.

BACKGROUND AND AIM: Oxaliplatin can lead to hepatic sinusoidal injury, called hepatic sinusoidal obstruction syndrome (SOS), resulting in portal hypertension-related complications. This could worsen the clinical course of the patients treated with oxaliplatin. Early diagnosis is challenging. We explored predictive markers of oxaliplatin-induced collateral vessels. METHODS: Patients who received oxaliplatin-based chemotherapy were retrospectively screened. We evaluated their laboratory findings and spleen size on computed tomography immediately before oxaliplatin-based chemotherapy and after 6 months of treatment. The primary outcome was collateral vessel development, as a surrogate marker for oxaliplatin-induced SOS in patients who underwent oxaliplatin-based chemotherapy. The secondary outcome was the identification of factors that predicted the development of collateral vessels. RESULTS: We enrolled 161 patients who received oxaliplatin-based chemotherapy. They had a median age of 69 years, and 63.3% were men. Collateral vessels developed in nine (5.6%) patients during the study period. After oxaliplatin-based chemotherapy, the spleen size increased in 104 patients (64.6%), with a ≥ 30% increase in 19.4% of the patients. Univariate analysis showed that the Fibrosis-4 (FIB-4) index (≥ 1.76; OR 9.17), aspartate aminotransferase:platelet ratio index (APRI) (≥ 0.193; OR 9.62), cumulative dose of oxaliplatin (≥ 1000 mg; OR 8.43), and increase in spleen size (≥ 30%; OR 6.01) were significant risk factors for collateral vessel development. Multivariate analysis after stepwise selection revealed that the FIB-4 index and spleen size were significant independent predictive factors. CONCLUSION: A ≥ 1.76 increase in the FIB-4 index and a ≥ 30% increase in spleen size after 6 months of oxaliplatin-based chemotherapy were significant predictive markers for collateral vessel development.

Classification and clinical features of adverse drug reactions in patients with ulcerative colitis treated with 5-aminosalicylate acid: a single-center, observational study.

BACKGROUND: 5-Aminosalicylate acid (5-ASA) is a crucial drug for ulcerative colitis (UC) patients. 5-ASA has several side effects. However, the types of side effects vary and are sometimes severe. METHODS: A single-center, retrospective cohort study was conducted from September 2001 to June 2020. We surveyed consecutive UC patients who visited our hospital and investigated adverse drug reactions (ADRs) related to 5-ASA formulations. We grouped patients into four subgroups: (1) lupus-like symptoms, (2) blood test abnormalities, (3) mimicking IBD exacerbation and (4) others. Their clinical courses were evaluated. RESULTS: We surveyed 288 consecutive UC patients, 35 of whom developed ADRs of any grade (12.9%), and analyzed 27 patients. The median age and 5-ASA doses were 43 years and 4000 mg, respectively, and 48% were male. The ADR triggers were the first use of 5-ASA (n = 17, 63%), 5-ASA switch (n = 9, 33%) and 5-ASA dose escalation (n = 1, 3.7%). The median time to ADR was 15 days (IQR: 7, 63). Ten patients (37%) had grade 3/4 ADRs. Fever was the most common ADR (n = 6, 23%), followed by hyperamylasemia and headache (n = 4, 15%). Lupus-like symptoms accounted for 56% (n = 15), blood test abnormalities for 26% (n = 7), mimicking IBD exacerbation for 15% (n = 4) and others for 3.7% (n = 1). The time to ADR was shorter in the mimicking IBD exacerbation group (median 11 days) than in the lupus-like symptoms (22 days) and blood test abnormalities (55 days) groups. CONCLUSION: Classification of ADRs related to 5-ASA into four groups might lead to early recognition of ADRs.

Prognostic impact of worsening of esophageal varices after balloon-occluded retrograde transvenous obliteration.

BACKGROUND AND AIM: Balloon-occluded retrograde transvenous obliteration (BRTO) is widely performed for treating gastric varices (GVs). However, worsening of esophageal varices (EVs) can be observed after BRTO. This study aimed to investigate the impact of EV worsening on prognosis after BRTO. METHODS: Overall, 258 patients who underwent initial BRTO for GV treatment between January 2004 and May 2019 at 12 institutions were retrospectively registered. RESULTS: Technical success was achieved in 235 patients (91.1%). Based on the exclusion criteria, 37 patients were excluded, and 198 were evaluated. The cumulative worsening rates of EVs at 1, 2, and 3 years were 39.0%, 59.4%, and 68.4%, respectively. In the univariate Cox proportional hazards model, sex, EV size, history of EV treatment, left gastric vein dilatation, platelet count, aspartate transaminase (AST), alanine aminotransferase (ALT), total bilirubin, albumin, albumin-bilirubin score, prothrombin time-international normalized ratio, fibrosis-4 index, AST to platelet ratio index, and spleen width were significantly associated with worsening of EV after BRTO. Multivariate analysis showed that sex (adjusted hazard ratio [aHR] 1.72; 95% confidence interval [CI] 1.03-2.86; P = 0.04), left gastric vein dilatation (aHR 1.90; 95% CI 1.17-3.10; P = 0.01), ALT (aHR 1.01; 95% CI 1.00-1.03; P = 0.02), albumin (aHR 0.61; 95% CI 0.43-0.87; P < 0.01), and spleen width (aHR 1.02; 95% CI 1.01-1.03; P < 0.01) were independent risk factors for worsening of EV after BRTO. Patients with EV worsening within 1 year after BRTO had a significantly worse prognosis than the other patients (P = 0.007). CONCLUSIONS: Early worsening of EV after BRTO was associated with poor prognosis after BRTO.

Time Trend of the Radiation Exposure Dose in Endoscopic Retrograde Cholangiopancreatography Over an 8-Year Period: A Single-Center Retrospective Study.

INTRODUCTION: The global needs for a reduction in radiation exposure (RE) are increasing. Endoscopic retrograde cholangiopancreatography (ERCP) is a significant fluoroscopic procedure in the gastrointestinal field. However, the actual RE in ERCP and its annual trend are still unclear. Therefore, we examined the yearly trend of RE in ERCP. METHODS: This retrospective, single-center cohort study included consecutive cases of ERCP from September 2012 to June 2019. We measured the air kerma (AK, mGy), dose area product (DAP, Gycm2), and fluoroscopy time (FT, min). We also evaluated the annual trend of the RE before and after the fluoroscopy device update. RESULTS: In total, 2,174 patients receiving ERCP were enrolled. Among these, the mean age was 74.3 years, and 913 patients were women (42.0%). The median/third quartile values of AK (mGy), DAP (Gycm2), and FT (min) were 109/234 mGy, 13.3/25.8 Gycm2, and 18.2/27.7 minutes. The annual AK, DAP, and FT from 2012 to 2019 were 138, 207, 173, 177, 106, 71.0, 45.0, and 33.3 mGy; 23, 21.4, 19, 18.3, 11.9, 9.0, 6.8, and 6.4 Gycm2; and 12.5, 12.1, 9.7, 9.8, 8.2, 10.8, 9.4, and 10.3 minutes, respectively. The corresponding values before and after the update in July 2016 were 177 and 52 mGy (P < 0.0001), 19.2 and 7.6 Gycm2 (P < 0.0001), and 10.2, and 9.9 minutes (P = 0.05), respectively. DISCUSSION: The RE from ERCP tended to decrease every year, especially after fluoroscopy device updates.

Breeding and characterization of the world's first practical rice variety with resistance to brown spot (Bipolaris oryzae) bred using marker-assisted selection.

Brown spot (BS) caused by Bipolaris oryzae is a serious disease of rice and decreases grain yield. Breeding for BS resistance is an economical solution but has not hitherto been achieved. To develop a practical BS-resistant variety, we introduced a chromosomal segment including a quantitative trait locus (QTL) for BS resistance, qBSfR11, derived from the BS-resistant local resource 'Tadukan', into the genetic background of the high-yielding but susceptible 'Mienoyume'. Resistance is controlled by a single recessive gene in a 1.3-Mbp region. We named this gene bsr1 (brown spot resistance 1). The near-isogenic line bsr1-NIL had a greater yield with larger grain width than Mienoyume but similar other agronomic traits in fields where BS was mild; it had a significantly lower BS disease score and a 28.8% higher yield in fields where BS was more severe, and it showed resistance to multiple isolates of BS fungus. It showed stable resistance to BS and had excellent agricultural traits in the presence of BS. We developed the bsr1-NIL with resistance to BS and applied it for variety registration to Ministry of Agriculture, Forestry and Fisheries in Japan as 'Mienoyume BSL'. This is the first report for the BS resistant rice variety bred using marker-assisted selection.

QTL analysis for brown spot resistance in American rice cultivar 'Dawn'.

Rice brown spot (BS), caused by Bipolaris oryzae, causes yield loss and deterioration of grain quality. Using single-nucleotide polymorphism (SNP) markers, we conducted quantitative trait locus (QTL) analysis of BS resistance in backcross inbred lines (BILs) from a cross between an American rice cultivar, 'Dawn' (resistant), and 'Koshihikari' (susceptible). Four QTLs for BS resistance were detected in a three-year field evaluation, and 'Dawn' contributed the resistance alleles at all QTLs. The QTL with the greatest effect, qBSR6-kd, explained 15.1% to 20.3% of the total phenotypic variation. Although disease score and days to heading (DTH) were negatively correlated in all three years, qBSR6-kd was located near a QTL for DTH at which the 'Dawn' allele promoted heading. Another BS resistance QTL (qBSR3.1-kd) was unlinked to the QTLs for DTH. Therefore, these two QTLs are likely to be useful for breeding BS-resistant varieties without delaying heading. The other two BS resistance QTLs (qBSR3.2-kd and qBSR7-kd) were located near DTH QTLs at which the 'Dawn' alleles delayed heading. The QTLs reported here will be good candidates for developing BS-resistant cultivars.

Effect of Iontophoresis on the Intradermal Migration Rate of Medium Molecular Weight Drugs.

The purpose of the present study was to evaluate whether iontophoresis (IP) accelerates the intradermal migration rate of medium molecular weight drugs. Sodium polystyrene sulfonate (PSA) and fluorescein isothiocyanate-dextran (FD) were used as model medium molecular weight acidic and non-electrolyte drugs, respectively. Low molecular weight acid and non-electrolyte drugs were also used for comparison. Drug-loaded excised split-layered skin (SL skin) was used in the experiment. SL skin was prepared using (i) whole skin was split once, (ii) the drug solution was applied on the lower skin, and (iii) the upper skin was layered onto the lower skin containing the drug solution as in the original skin. The effect of constant-current cathodal or anodal IP was applied to the SL skin, and the time course of the cumulative amount of drug migration from the SL skin through the dermis to the receiver was followed. In cases without IP and with anodal IP, the intradermal migration rates of medium molecular weight drugs were much lower than those of small molecules. The driving force for drug migration was thought to be simple diffusion through the skin layer. In contrast, cathodal IP significantly increased the intradermal migration rate of PSA not but of FD or low molecular weight drugs. This IP-facilitated migration of PSA was probably due to electrorepulsion. These results suggest that IP can be used to increase the intradermal migration of medium molecular weight charged drugs.

Acute intracerebroventricular injection of chemerin-9 increases systemic blood pressure through activating sympathetic nerves via CMKLR1 in brain.

Chemerin is an adipocytokine involved in inflammation and lipid metabolism via G protein-coupled receptor, chemokine-like receptor (CMKLR)1. Since the important nuclei regulating pressure (BP) exist in the brain, we examined the effects of acute intracerebroventricular (i.c.v.) injection of chemerin-9 on systemic BP and explored underlying mechanisms. We examined the effects of acute i.c.v. injection of chemerin-9 (10 nmol/head) on systemic BP by a carotid cannulation method in the control or CMKLR1 small interfering (si) RNA-treated Wistar rats (0.04 nmol, 3 days, i.c.v.). We examined protein expression of CMKLR1 around brain ventricles by Western blotting. We examined the effects of acute i.c.v. injection of chemerin-9 on serum adrenaline by a high performance liquid chromatography. In the control siRNA-treated rats, chemerin-9 significantly increased mean BP, which reached a peak at 2 to 4 min after injection. On the other hand, in the CMKLR1 siRNA-treated rats, chemerin-9 did not affect the mean BP. Protein expression of CMKLR1 specifically in subfornical organ (SFO) and paraventricular nucleus (PVN) from the CMKLR1 siRNA-treated rats decreased compared with the control siRNA-treated rats. In the control siRNA-treated rats, chemerin-9 increased serum adrenaline level. On the other hand, in the CMKLR1 siRNA-treated rats, chemerin-9 did not affect the serum adrenaline level. Further, pretreatment with prazosin, an α-adrenaline receptor blocker, significantly prevented the pressor responses induced by chemerin-9. In summary, we for the first time demonstrated that chemerin-9 stimulates the sympathetic nerves via CMKLR1 perhaps expressed in SFO and PVN, which leads to an increase in systemic BP.

Claudin-3 regulates bile canalicular paracellular barrier and cholesterol gallstone core formation in mice.

BACKGROUND & AIMS: Most cholesterol gallstones have a core consisting of inorganic and/or organic calcium salts, although the mechanisms of core formation are poorly understood. We examined whether the paracellular permeability of ions at hepatic tight junctions is involved in the core formation of cholesterol gallstones, with particular interest in the role of phosphate ion, a common food additive and preservative. METHODS: We focused on claudin-3 (Cldn3), a paracellular barrier-forming tight junction protein whose expression in mouse liver decreases with age. Since Cldn3-knockout mice exhibited gallstone diseases, we used them to assess the causal relationship between paracellular phosphate ion permeability and the core formation of cholesterol gallstones. RESULTS: In the liver of Cldn3-knockout mice, the paracellular phosphate ion permeability through hepatic tight junctions was significantly increased, resulting in calcium phosphate core formation. Cholesterol overdose caused cholesterol gallstone disease in these mice. CONCLUSION: We revealed that in the hepatobiliary system, Cldn3 functions as a paracellular barrier for phosphate ions, to help maintain biliary ion homeostasis. We provide in vivo evidence that elevated phosphate ion concentrations play a major role in the lifestyle- and age-related risks of developing cholesterol gallstone disease under cholesterol overdose. LAY SUMMARY: Herein, we reveal a new mechanism for cholesterol gallstone formation, in which increased paracellular phosphate ion permeability across hepatobiliary epithelia causes calcium phosphate core formation and cholesterol gallstones. Thus, altered phosphate ion metabolism under cholesterol overdose plays a major role in the lifestyle- and age-related risks of developing cholesterol gallstone disease.

Plasma exosomes regulate systemic blood pressure in rats.

Exosomes, the smallest extracellular vesicle, contain various molecules and mediate cell-cell communication. A number of studies demonstrate exosomes are involved in important physiological and pathological processes. Moreover, microRNA (miRNA) regulating hypertension development through the suppression of certain translation was recently reported. However, roles of exosomes containing various molecules including miRNA on development of essential hypertension have not been examined. We tested the hypothesis that plasma exosomes regulate systemic blood pressure in normotensive and spontaneously hypertensive rats (SHR). Normotensive Wistar Kyoto rats (WKY) and SHR (5-10-week-old) were intraperitoneally administrated with exosomes derived from plasma in WKY or SHR weekly for 6 weeks. Exosomes were isolated by an ultracentrifuge method. SHR-derived exosomes significantly increased systolic blood pressure in WKY, while WKY-derived exosomes decreased it in SHR. In WKY, SHR-derived exosomes induced modest structural changes of thoracic aorta, such as wall thickening and decreased abundance of collagen, which were similar to the changes observed in SHR. On the contrary, WKY-derived exosomes tended to reverse the changes in SHR. WKY-derived exosomes significantly suppressed the increased prostaglandin F2α-induced contraction of mesenteric arterial smooth muscle in SHR. In addition, wet weight and perivascular fibrosis of left ventricles in WKY were significantly increased by SHR-derived exosomes, while the fibrosis but not ventricular weight was significantly decreased by WKY-derived exosomes in SHR. We for the first time demonstrated that plasma exosomes can modulate systemic blood pressure as well as structure and function of cardiovascular tissues in both normotensive and hypertensive rats.

Dissolving Microneedles as Skin Allergy Test Device.

The possibility of using dissolving microneedles (DMs) as a skin allergy test device was studied in rats. Poly-L-arginine was used as a model allergen. Dextran was used to prepare three kinds of DM array chips containing different doses of poly-L-arginine: 17.1±0.5 µg (low-dose DM), 42.2±0.8 µg (medium-dose DM), and 87.4±1.1 µg (high-dose DM); each 1.0 cm2 chip contained 300 DMs. The mean lengths of the low-, medium-, and high-dose DM were 489±3, 485±3, and 492±1 µm and mean diameters of the base were 301±2, 299±1, and 299±2 µm, respectively. Furthermore, for the low-, medium-, and high-dose DM, the administered doses of poly-L-arginine were estimated to be 9.3±1.9, 31.1±1.3, and 61.9±4.7 µg and the scratching behavior per 30 min was 9.8±3.4, 60.4±8.3, and 95.7±10.6 times, respectively. These results demonstrate the dose dependence of the immunoreactivity of the poly-L-arginine DMs, suggesting that DMs can be used an alternative skin allergy device.

Identification of QTLs for rice brown spot resistance in backcross inbred lines derived from a cross between Koshihikari and CH45.

Rice brown spot (BS), caused by Bipolaris oryzae, is one of the major diseases of rice in Japan. Quantitative resistance has been observed in local cultivars (e.g., CH45), but no economically useful resistant variety has been bred. Using simple sequence repeat (SSR) polymorphic markers, we conducted quantitative trait locus (QTL) analysis of BS resistance in backcross inbred lines (BILs) from a cross between indica CH45 (resistant) and japonica Koshihikari (susceptible). On the basis of field disease evaluations in 2015 and 2016, four QTLs contributing to BS resistance were identified on chromosomes 2 (qBSR2-kc), 7 (qBSR7-kc), 9 (qBSR9-kc), and 11 (qBSR11-kc). The 'CH45' alleles at qBSR2-kc, qBSR7-kc, and qBSR11-kc and the 'Koshihikari' allele at qBSR9-kc increased resistance. The major QTL qBSR11-kc explained 23.0%-25.9% of the total phenotypic variation. Two QTLs (qBSR9-kc and qBSR11-kc) were detected in both years, whereas the other two were detected only in 2016. Genetic markers flanking these four QTLs will be powerful tools for marker-assisted selection to improve BS resistance.