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A methanolic extract of Citrus unshiu induces oviposition by females of a Citrus-feeding swallowtail butterfly, Papilio xuthus L. The chemical factors responsible for stimulating oviposition were isolated and characterized as 5-hydroxy- Nω-methyltryptamine, adenosine, vicenin-2, narirutin, hesperidin and rutin. An artificial blend of these six components elicited significant oviposition behavior, apparently identical to that induced by contact with intact Citrus leaves. [ABSTRACT FROM AUTHOR]

While screening for antibiotics in a marine sample, we discovered a berninamycin C-producing actinomycete, designated YSPA8 T , isolated from a sponge. A polyphasic approach was used to determine the taxonomic position of the strain. Strain YSPA8 T formed sympodially branched aerial mycelia that ultimately segment into chains of spores. Comparative and phylogenetic analyses of the 16S rRNA gene sequence showed that strain YSPA8 T were closely related to Streptomyces clavuligerus ATCC 27064 T (99.66%), Streptomyces amakusaensis NRRL B-3351 T (98.69%), Streptomyces inusitatus NBRC 13601 T (98.48%), and 'Streptomyces jumonjinensis' JCM 4947 (98.41%). The phylogenetic tree using the 16S rRNA gene sequences, and both phylogenomic trees suggested that the closest relative of strain YSPA8 T was S. clavuligerus ATCC 27064 T . The average nucleotide identity, digital DNA-DNA hybridization, and average amino acid identity values between strain YSPA8 T and S. clavuligerus ATCC 27064 T were 84.1%, 28.9%, and 82.5%, respectively, which were below the thresholds of 95%, 70%, and 95% for a prokaryotic conspecific assignment. The G + C of the strain YSPA8 T was 72.6%. Whole-cell hydrolysates of strain YSPA8 T contained LL-diaminopimelic acid. The predominant menaquinones were MK-9(H 6 ) (49%) and MK-9(H 8 ) (48%), and the major fatty acids were C 16:0 (26.8%), C 16:1 ω7c/ω6c (17.2%), iso-C 16:0 (16.0%), and iso-C 15:0 (12.5%). The major phospholipids were diphosphatidylglycerol, phosphatidylethanolamine, and other unidentified phospholipids. Based on the phenotypic, phylogenetic, genomic, and chemotaxonomic data, strain YSPA8 T represents a novel species of the genus Streptomyces, and the proposed name for this species is Streptomyces yaizuensis sp. nov. The type strain is YSPA8 T (=NBRC 115866 T  = TBRC 17196 T )., Competing Interests: Compliance with ethical standards. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to the Japan Antibiotics Research Association.)

A 71-year-old man underwent endoscopic mucosal resection(EMR)of a sigmoid colon polyp 7 years ago. The pathological result was adenocarcinoma(pap+tub2+tub1), pTis, ly(-), v(-). Then he was under observation. This time, a 20 mm submucosal tumor-like finding was found near the scar after EMR, and a biopsy revealed a diagnosis of adenocarcinoma (tub2). CT scan showed lymphadenopathy beside sigmoid colon. There were no non-resectable factors, so a laparoscopic sigmoid resection was performed. The pathological result showed adenocarcinoma(tub2), and although some parts were continuous with the mucosa, the majority of the tumor was located from submucosa to subserosa, and it was diagnosed as direct invasion into the lymph nodes outside the wall, and the possibility of lymph node recurrence was suspected. He underwent adjuvant chemotherapy CAPOX. In order to establish the optimal surveillance of colon carcinoma in situ, it is important to accumulate further cases and evidence.

A 74-year-old woman underwent colonoscopy for positive fecal occult blood test. A colonoscopy revealed a Type 1 tumor in the rectosigmoid region. The tumor was diagnosed as well-differentiated adenocarcinoma(tub1)by biopsy. Laparoscopic high anterior resection was performed. The final diagnosis was MiNEN(adenocarcinoma:NEC=6:4), RS, pT4a(SE), INF c, Ly1c, V1b, Pn1b, BD2, pN2a(5/28), cM0, pStage Ⅲc. All lymph node metastases were of NEC origin. This case was considered to be at high risk of recurrence and require adjuvant chemotherapy focused on NEC. She was referred to an advanced medical institution for carboplatin and etoposide therapy. MiNEN is a rare disease, and has a poor prognosis. In order to establish a therapeutic strategy of MiNEN, it is important to accumulate further cases and evidence.

A man in his seventies underwent endoscopic mucosal resection(EMR)of a rectal cancer 3 years ago. Histopathological examination showed that the specimen had been resected curatively. However, a routine follow-up colonoscopy revealed a submucosal mass on the EMR scar. Computed tomography imaging revealed a mass in the posterior wall of the rectum, with suspected invasion of the sacrum. We performed a biopsy during endoscopic ultrasonography and diagnosed a local recurrence of the rectal cancer. After preoperative chemoradiotherapy(CRT), laparoscopic low anterior resection with ileostomy was performed. Histopathological examination revealed invasion of the rectal wall from the muscularis propria to the adventitia and tissue fibrosis at the radial margin, which was devoid of cancerous cells. Subsequently, the patient received adjuvant chemotherapy with uracil/tegafur and leucovorin for 6 months. No recurrence has been reported over a postoperative follow- up period of 4 years. Preoperative CRT may be an effective treatment for locally recurrent rectal cancer after endoscopic resection.

Objectives: There is limited information on the clinical use of Janus kinase inhibitors (JAKis) for rheumatoid arthritis treatment in Japan. The aim of this study was to identify disease-modifying antirheumatic drug (DMARD) treatment patterns in Japan., Methods: This retrospective, longitudinal study extracted data from the Japan Medical Data Center database. Patients with rheumatoid arthritis diagnosis were enrolled 2016-19, during which patients had a first prescription of a major DMARD, split into six mutually exclusive classes: methotrexate (MTX); other conventional synthetic DMARDs; tumour necrosis factor alpha inhibitors; cytotoxic T-lymphocyte-associated antigen-4-immunoglobulin; anti-interleukin-6 receptor therapies; and JAKis. The primary objective was to describe DMARD treatment patterns, especially for JAKis., Results: Overall, 10,399 patients were included in the analysis. The most common treatments were MTX, other conventional synthetic DMARDs, and tumour necrosis factor alpha inhibitors. The total number of JAKi prescriptions increased approximately 8-fold during 2016-19. Most (61.1%) patients who received JAKis had prior MTX or tumour necrosis factor alpha inhibitor treatment. The duration of JAKi treatment was longer than for biologics and other conventional synthetic DMARDs and comparable to that of MTX., Conclusions: The sequence of drug class prescriptions for rheumatoid arthritis in Japan during 2016-19 followed clinical guidelines. Over this period, JAKis were increasingly used as a second-line treatment following MTX., (© Japan College of Rheumatology 2022. Published by Oxford University Press.)

A polyphasic approach was used to determine the taxonomic position of a marine actinomycete, designated isolate CWH03 T , which we previously reported to produce new linear azole-containing peptides spongiicolazolicins A and B. Strain CWH03 T is mesophilic, neutrophilic, and halotolerant streptomycete that forms spiral spore chains on aerial mycelium. Comparative 16S rRNA gene sequencing showed that CWH03 T was most closely related to Streptomyces tirandamycinicus HNM0039 T (99.7%), Streptomyces spongiicola HNM0071 T (99.4%), 'Streptomyces marianii' ICN19 T (99.1%) and Streptomyces wuyuanensis CGMCC4.7042 T (99.0%). The phylogenetic tree prepared using the 16S rRNA gene, as well as the phylogenomic tree using the genome BLAST distance phylogeny method and 81 core housekeeping genes, respectively, showed that the closest relative of strain CWH03 T was S. spongiicola HNM0071 T . The average nucleotide identity and digital DNA-DNA hybridization values between strains CWH03 T and S. spongiicola HNM0071 T were 91.46% and 44.2%, respectively, which were below the thresholds of 96% and 70% for prokaryotic conspecific assignation. The G+C content of the genomic DNA of strain CWH03 T was 72.3%. Whole-cell hydrolysates of strain CWH03 T contained LL-diaminopimelic acid. The predominant menaquinone was MK-9(H 8 ) (88.3%), and the major fatty acids were iso-C 16:0 (28.4%), anteiso-C 15:0 (15.0%) and iso-C 15:0 (12.9%). The major phospholipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and an unidentified phospholipid. Based on data obtained from phenotypic, phylogenetic, genomic, and chemotaxonomic analyses, strain CWH03 T represents a novel species of the genus Streptomyces, for which the proposed name is Streptomyces pacificus sp. nov. The type strain is CWH03 T ( = NBRC 114659 T  = TBRC 15780 T )., (© 2022. The Author(s), under exclusive licence to the Japan Antibiotics Research Association.)

Background: Phase-contrast X-ray computed tomography imaging (PCI) based on crystal X-ray interferometry can detect minute density differences within biological soft tissues without contrast agents. Ethanol fixation yields increased tissue-background density differences due to the dehydrating and delipidifying effects of ethanol., Purpose: To obtain high image contrast of cerebral white matter structures in PCI, tissue fixation using ethanol and routinely used formalin have been examined., Material and Methods: Ethanol-fixed (EF) (n = 4) and formalin-fixed (FF) (n = 4) rat brains were imaged by crystal X-ray interferometry-based PCI. Tissue staining/microscopy was also performed for histological comparison and myelin density evaluation. Three-dimensional white matter tract images were reconstructed., Results: Superior image contrast was obtained in the images of EF brains (EF images) compared to those of formalin-fixed brains (FF images), particularly for white matter structures. Significant density differences between the white matter structures and hippocampus ( P  < 0.01)/thalamus ( P  < 0.001) were observed in the EF, but not FF, images. Ethanol fixation enhanced the image contrast of white matter tracts by approximately sixfold compared to formalin fixation, and close agreement (r 2  = 0.97; P  < 0.05) between the density values on the CT images and the myelin density values in histological images was observed for the EF brains. Three-dimensional reconstruction of the white matter tracts was possible from the EF images, but not FF images., Conclusion: Ethanol fixation resulted in marked contrast enhancement of cerebral white matter structures in PCI. Thus, high-resolution PCI using ethanol for tissue fixation could be valuable for experimental neurological studies and postmortem neuropathology evaluation.

Background: Neuroendocrine cell carcinomas (NEC) of the colon and rectum are uncommon, representing ~ 0.1% of all colorectal carcinomas. They are associated with a much worse prognosis compared to adenocarcinoma of the colon and rectum, as death occurs in approximately half of all patients within 1 year. Lynch syndrome (LS) is the most common cause of inherited colorectal cancer, accounting for 2-4% of newly diagnosed colorectal cancer cases. This case is extremely rare which was strongly suspected LS as the background, and NEC as the histological type of colorectal cancer., Case Presentation: The patient was a 44-year-old man presenting with vomiting as the main complaint. He had undergone ileocecal resection for cecal cancer at age 29. The diagnosis was obstructive descending colorectal cancer, and colonoscopy revealed tumors in the rectum and sigmoid colon in addition. Due to multiple occurrences of colorectal cancer and its prevalence in the patient's family, LS was suspected. The operation which was a subtotal proctocolectomy was performed. Pathological analysis revealed complete curative resection and the descending colon cancer of the obstructed portion was at the most advanced pathological Stage IIIC in UICC TNM classification, and the tissue type was a NEC. The Ki-67 index was 70%. The results of the microsatellite instability (MSI) test showed high-frequency MSI. The BRAF V600E variant was negative. The immunoexpression of MLH1 was positive, MSH2 was negative, PMS2 was positive, and MSH6 was negative., Conclusions: Extended surgery is recommended for incipient colorectal cancer in LS cases in order to reliably reduce the risk of developing metachronous colorectal cancer. The survival outcome of surgery alone on digestive tract NECs, even locoregional lesions that are completely resection, is extremely poor. It is currently unclear if digestive tract NECs develop more readily in patients with LS. The accumulation of additional cases is necessary., (© 2022. The Author(s).)

The ATP-binding cassette subfamily G member 2 (ABCG2) transporter is involved in the development of multidrug resistance in cancer patients. Many inhibitors of ABCG2 have been reported to enhance the chemosensitivity of cancer cells. However, none of these inhibitors are being used clinically. The aim of this study was to identify novel ABCG2 inhibitors by high-throughput screening of a chemical library. Among the 5812 compounds in the library, 23 compounds were selected in the first screening, using a fluorescent plate reader-based pheophorbide a (PhA) efflux assay. Thereafter, to validate these compounds, a flow cytometry-based PhA efflux assay was performed and 16 compounds were identified as potential inhibitors. A cytotoxic assay was then performed to assess the effect these 16 compounds had on ABCG2-mediated chemosensitivity. We found that the phenylfurocoumarin derivative (R)-9-(3,4-dimethoxyphenyl)-4-((3,3-dimethyloxiran-2-yl)methoxy)-7H-furo [3,2-g]chromen-7-one (PFC) significantly decreased the IC 50 of SN-38 in HCT-116/BCRP colon cancer cells. In addition, PFC stimulated ABCG2-mediated ATP hydrolysis, suggesting that this compound interacts with the substrate-binding site of ABCG2. Furthermore, PFC reversed the resistance to irinotecan without causing toxicity in the ABCG2-overexpressing HCT-116/BCRP cell xenograft mouse model. In conclusion, PFC is a novel inhibitor of ABCG2 and has promise as a therapeutic to overcome ABCG2-mediated MDR, to improve the efficiency of cancer chemotherapy.

We present the case of a 67-year-old man in good health with perirenal hematoma due to a ruptured arterial aneurysm in the kidney. The patient developed weight loss, muscle weakness, multiple mononeuropathy, hypertension, anemia, renal insufficiency, and multiple lacuna infarctions about a month ago. He was admitted to the hospital due to worsening of his symptom. After admission, severe right-flank pain suddenly occurred; he was then transferred to our hospital. Renal angiography revealed bilateral multiple microaneurysms, and the patient was diagnosed with polyarteritis nodosa based on the clinical, radiographic, and histological findings. We performed selective coil embolization to the ruptured aneurysm and administered oral prednisolone along with intravenous methylprednisolone pulse therapy. Cyclophosphamide pulse therapy was also given. The treatment improved clinical and laboratory findings and achieved clinical remission. Selective coil embolization to the bleeding aneurysm of polyarteritis nodosa was minimally invasive and promptly effective. Immunosuppressants proved useful in the regulation of disease activity and the aneurysm.

A 65-year-old male was diagnosed with rectal cancer invading the urinary bladder, swollen para-aorticlymph nodes, and multiple liver metastases in abdominal CT. After 8 courses of mFOLFOX6 plus panitumumab, the rectal cancer, para-aortic lymph nodes metastasis, and liver metastases decreased significantly in size. Rectal cancer and liver metastases were considered resectable, hence low anterior resection of the rectum was performed. Intraoperative frozen section analysis showed negative metastaticinvolvement of the para-aorticlymph nodes and surgical margins of the urinary bladder; therefore, the urinary bladder was completely preserved. Partial resection of the liver was performed 2 months later. In conclusion, the patient showed good surgical and quality of life results. Thus, the bladder-sparing strategy with preoperative chemotherapy could be considered for appropriately selected rectal cancer patients with urinary bladder involvement.

In inflammatory bowel disease, chronic inflammation results in the development of colon cancer known as colitis-associated cancer. This disease is associated with tumor necrosis factor-α (TNF-α) signaling. In addition, intestinal fibrosis is a common clinical complication that is promoted by transforming growth factor β1 (TGF-β 1 ). In our previous study, MA-35 attenuated renal fibrosis by inhibiting both TNF-α and TGF-β 1 signaling. This study aimed to identify the possible antitumor effects and antifibrotic effects of MA-35 using an AOM/DSS mouse model. MA-35 was orally administered every day for 70 days in the AOM/DSS mouse model. There was no difference in weight loss between the AOM/DSS group and the AOMDSS + MA-35 group, but the disease activity index score and the survival rate were improved by MA-35. MA-35 blocked the anemia and shortening of the colon induced by AOM/DSS. MA-35 reduced the macroscopic formation of tumors in the colon. In the microscopic evaluation, MA-35 reduced inflammation and fibrosis in areas with dysplasia. Furthermore, the TNF-α mRNA level in the colon tended to be reduced, and the interleukin 6, TGF-β 1 and fibronectin 1 mRNA levels in the colon were significantly reduced by MA-35. These results suggested that MA-35 inhibited AOM/DSS-induced carcinogenesis by reducing inflammation and fibrosis.

According to the treatment guideline for rectal neuroendocrine tumor(NET), tumor with a diameter ofC10mm should be resected endoscopically, while tumor with a diameter of>10mm should be resected surgically with lymph node dissection. We experienced a case of a rectal NET with a diameter of 5mm with lymph node metastasis. A 69-year-old man underwent colonoscopy for positive fecal occult blood test. The colonoscopy revealed a submucosal tumor(SMT)with a diameter of 5 mm in the lower rectum. An endoscopic mucosal resection(EMR)was performed after SMT was diagnosed as NET by biopsy. Histopathological findings were NET-G1, 4.5×2.5 mm, v(+), ly(+). Then, laparoscopically assisted rectal resection with D2 lymph node dissection was performed. In histopathological examination, no tumor residue was observed in the specimu; however, a regional lymph node metastasis was detected. Risk factors of lymph node metastasis with rectal NET are a diameter of>10 mm, recessed or ulcerated surface, and lymphovascular invasion. However, we have to keep in mind that lymph node metastasis may occur even in small rectal NET with a diameter of ≤10mm.

Background: This is a subgroup analysis of Korean patients from a phase 3 clinical trial investigating the efficacy and safety of ipragliflozin in patients with type 2 diabetes mellitus inadequately controlled with metformin., Methods: This multicenter, placebo-controlled, double-blind, parallel-group study was carried out between November 2011 and January 2013. Patients entered a 2-week placebo pretreatment period, followed by a 24-week treatment period with either ipragliflozin (50 mg/day) or placebo, while continuing metformin. Efficacy outcomes (glycosylated hemoglobin [HbA1c], fasting plasma glucose [FPG], and body weight) and safety outcomes (treatment-emergent adverse events [TEAEs]) were measured and compared between the two treatment groups for patients enrolled in all 18 study sites in Korea., Results: Eighty-two Korean patients received ipragliflozin (n=43) or placebo (n=39) during the study period. Mean changes in HbA1c levels from baseline to the end of treatment were -0.97% in the ipragliflozin group and -0.31% in the placebo group, with an adjusted between-group difference of -0.60% (P<0.001). Compared to placebo, FPG and body weight also decreased significantly (both P<0.001) from baseline after treatment in the ipragliflozin group, with between-group differences of -21.4 mg/dL and -1.53 kg, respectively. Decreased weight was the most common TEAE in the ipragliflozin group (7.0%); there were no reports of genital and urinary tract infection., Conclusion: Ipragliflozin treatment in addition to metformin led to significant improvement in glycemic outcomes and reduction in body weight in Korean patients with type 2 diabetes mellitus, compared with metformin treatment alone; the safety profile was comparable in both groups., Competing Interests: K.W.M., B.J.K., J.H.L., M.S.K., K.J.A., M.K.L., and B.S.C. have received research funding from Astellas Pharma Inc. S.K. and S.Y. are employees of Astellas Pharma Inc., Tokyo, Japan. H.J.C. is an employee of Astellas Korea Inc., Seoul, Korea. This study was sponsored by Astellas Pharma Inc., Japan. Medical writing and editorial support was funded by Astellas and provided by Hui Hwa Choo, Bao Hui Lee, and Naina Sharma from Research2Trials Clinical Solutions Pte. Ltd., (Copyright © 2017 Korean Diabetes Association)