RESUMO
Elevated autophagy activity enhances the malignancy of pancreatic cancer (PaCa), and autophagy is recognized as a novel therapeutic target. Zinc finger protein with KRAB and SCAN domains 3 (ZKSCAN3) is a transcription factor that suppresses autophagy, but its association with PaCa is unknown. We analyzed the function of ZKSCAN3 in PaCa and investigated whether autophagy regulation through ZKSCAN3 could become a new therapeutic target for PaCa. Using reverse transcription-quantitative polymerase chain reaction and western blotting, we observed that ZKSCAN3 expression was upregulated in several PaCa cell lines compared with normal pancreatic ductal epithelial cells. Additionally, comparing ZKSCAN3 expression with the prognosis of PaCa patients using web databases, we found that higher ZKSCAN3 expression in PaCa was associated with extended overall survival. Knocking down ZKSCAN3 promoted the proliferation of PaCa cells. Moreover, following ZKSCAN3 knockdown, PaCa cells exhibited significantly enhanced migratory and invasive properties. Conversely, overexpression of ZKSCAN3 significantly suppressed the proliferation, migration and invasion of PaCa cells. Additionally, the knockdown of ZKSCAN3 increased the expression of LC3-II, a marker of autophagy, whereas ZKSCAN3 overexpression decreased LC3-II expression. In a xenograft mouse model, tumors formed by MIA PaCa-2 cells in which ZKSCAN3 was knocked down significantly increased in size compared with the control group. In conclusion, ZKSCAN3 expression was upregulated in several pancreatic cancer cells. Additionally, it was revealed that ZKSCAN3 is negatively correlated with the malignancy of PaCa through autophagy. These results suggest that autophagy regulation via ZKSCAN3 may be a new therapeutic target for PaCa.
Assuntos
Autofagia , Movimento Celular , Proliferação de Células , Invasividade Neoplásica , Neoplasias Pancreáticas , Fatores de Transcrição , Humanos , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/genética , Autofagia/genética , Animais , Proliferação de Células/genética , Movimento Celular/genética , Linhagem Celular Tumoral , Camundongos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Regulação Neoplásica da Expressão Gênica , Camundongos Nus , Prognóstico , Feminino , Técnicas de Silenciamento de Genes , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas Associadas aos Microtúbulos/genéticaRESUMO
BACKGROUND: Data on concomitant mitral regurgitation (MR) in patients with severe aortic stenosis (AS) are scarce.MethodsâandâResults: We investigated the risk of concomitant MR in patients with severe AS in the CURRENT AS Registry-2 according to initial treatment strategy (transcatheter aortic valve implantation [TAVI], surgical aortic valve replacement [SAVR], or conservative). Among 3,365 patients with severe AS, 384 (11.4%) had moderate/severe MR (TAVI: n=126/1,148; SAVR: n=68/591; conservative: n=190/1,626). The cumulative 3-year incidence for death or heart failure (HF) hospitalization was significantly higher in the moderate/severe than no/mild MR group in the entire population (54.6% vs. 34.3%, respectively; P<0.001) and for each treatment strategy (TAVI: 45.0% vs. 31.8% [P=0.006]; SAVR: 31.9% vs. 18.7% [P<0.001]; conservative: 67.8% vs. 41.6% [P<0.001]). The higher adjusted risk of moderate/severe MR relative to no/mild MR for death or HF hospitalization was not significant in the entire population (hazard ratio [HR] 1.15; 95% confidence interval [CI] 0.95-1.39; P=0.15); however, the risk was significant in the SAVR (HR 1.92; 95% CI 1.04-3.56; P=0.04) and conservative (HR 1.30; 95% CI 1.02-1.67; P=0.04) groups, but not in the TAVI group (HR 1.03; 95% CI 0.70-1.52; P=0.86), despite no significant interaction (Pinteraction=0.37). CONCLUSIONS: Moderate/severe MR was associated with a higher risk for death or HF hospitalization in the initial SAVR and conservative strategies, while the association was less pronounced in the initial TAVI strategy.
RESUMO
BACKGROUND: The increased amount of contrast media in frequency-domain optical coherence tomography (FD-OCT) imaging during percutaneous coronary intervention (PCI) has raised potential concerns regarding impairment of renal function. OBJECTIVES: This study aimed to evaluate the effectiveness of heparinized saline flush in FD-OCT-guided PCI and identify clinical factors contributing to optimal image quality. METHODS: We retrospectively collected 100 lesions from 90 consecutive patients, and a total of 200 pullbacks were analyzed for the initial and final evaluation in which saline was used as the flushing medium. RESULTS: The study population had a mean age of 73, with 52% having chronic kidney disease (CKD). The median amount of contrast used was 28 ml, and no complications were observed associated with saline flush OCT. Imaging quality was then categorized as excellent, good, or unacceptable. Among the total runs, 87% demonstrated clinically acceptable image quality, with 66.5% classified as excellent images and 20.5% classified as good images. Independent predictors of excellent images included lumen area stenosis ≥ 70% (adjusted odds ratio [OR] 2.37, 95% confidence interval [CI] 1.02-5.47, P = 0.044), and the use of intensive flushing (adjusted OR 2.06, 95% CI 1.11-3.86, P = 0.023) defined as a deep engagement of guiding catheter (GC) or a selective insertion of guide extension catheter (GE). Intensive flushing was performed in 60% of the total pullbacks, and it was particularly effective in improving image quality in the left coronary artery (LCA). CONCLUSION: The use of saline flush during FD-OCT imaging was safe and feasible, which had a benefit in renal protection with adequate imaging quality.
Assuntos
Doença da Artéria Coronariana , Intervenção Coronária Percutânea , Humanos , Idoso , Tomografia de Coerência Óptica/métodos , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/terapia , Estudos Retrospectivos , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/patologia , Resultado do Tratamento , Angiografia Coronária , Valor Preditivo dos TestesRESUMO
It has been pointed out that robotic surgery is more time-consuming than laparoscopic surgery, and a major challenge for the future is educating young surgeons while maintaining the surgical quality. To solve these problems, we report a role-sharing surgery (RSS) approach in which the surgery is divided into several areas and timetabled, with roles shared by several operators. We performed RSS for 19 standard colorectal cancer surgeries. The surgery was completed within + 28 min of the scheduled operation time, and a beginner robotic surgeon (BRS) was able to perform approximately 66% of the total surgery. There were no statistically significant differences in the short-term outcomes between the RSS and conventional surgery groups. Based on these findings, RSS has the potential to be the best practice for educating BRSs in robotic surgery, the use of which is expected to increase steadily in the future.
Assuntos
Laparoscopia , Procedimentos Cirúrgicos Robóticos , Cirurgiões , Humanos , Procedimentos Cirúrgicos Robóticos/educação , Cirurgiões/educação , Laparoscopia/educaçãoRESUMO
The patient was a 68-year-old woman who was on hemodialysis due to systemic amyloidosis and nephrotic syndrome. Biopsy revealed amyloid deposition in the stomach, duodenum, and colon. A transverse colon tumor was found on a follow- up CT after the aortic dissection surgery. We performed lower gastrointestinal endoscopy and contrast-enhanced CT and diagnosed transverse colon cancer with gastric wall infiltration(cStage â ¢c). We considered that transverse colon resection was oncologically sufficient. However, due to concurrent gastrointestinal amyloidosis, which increased the risk of anastomotic leakage we performed laparoscopic extended right hemicolectomy to avoid colon-colon anastomosis with partial gastrectomy. Additionally intraoperative indocyanine green(ICG)fluorescence imaging showed that the fluorescence signal in the small intestinal wall was satisfactory, while it was weak in the colon wall. As a result, we suspected of impaired blood flow of colon wall due to an amyloidosis, so we additionally created a loop ileostomy. It is said that gastrointestinal amyloidosis raises the risk of anastomotic leakage. A case of transverse colon cancer complicated by gastrointestinal amyloidosis in which we successfully prevented anastomotic leakage through a multidimensional evaluation and approach is reported, along with a literature review.
Assuntos
Amiloidose , Colo Transverso , Neoplasias do Colo , Gastroenteropatias , Feminino , Humanos , Idoso , Fístula Anastomótica , Colo Transverso/cirurgia , Amiloidose/complicações , Amiloidose/cirurgia , Neoplasias do Colo/complicações , Neoplasias do Colo/cirurgiaRESUMO
BACKGROUND: Cisplatin-induced acute kidney injury (AKI) is common during preoperative chemotherapy for esophageal cancer. The purpose of this study was to investigate the association between AKI after preoperative chemotherapy and postoperative complications in patients with esophageal cancer. METHODS: In this retrospective cohort study, we included patients who had received preoperative chemotherapy with cisplatin and underwent surgical resection for esophageal cancer under general anesthesia from January 2017 to February 2022 at an education hospital. A predictor was stage 2 or higher cisplatin-induced AKI (c-AKI) defined by the KDIGO criteria within 10 days after chemotherapy. Outcomes were postoperative complications and length of hospital stays. Associations between c-AKI and outcomes including postoperative complications and length of hospital stays were examined with logistic regression models. RESULTS: Among 101 subjects, 22 developed c-AKI with full recovery of the estimated glomerular filtration (eGFR) before surgery. Demographics were not significantly different between patients with and without c-AKI. Patients with c-AKI had significantly longer hospital stays than those without c-AKI [mean (95% confidence interval (95%CI)) 27.6 days (23.3-31.9) and 43.8 days (26.5-61.2), respectively, mean difference (95%CI) 16.2 days (4.4-28.1)]. Those with c-AKI had higher C-reactive protein (CRP) levels and prolonged weight gain after surgery and before the events of interest despite having comparable eGFR trajectories after surgery. c-AKI was significantly associated with anastomotic leakage and postoperative pneumonia [odds ratios (95%CI) 4.14 (1.30-13.18) and 3.87 (1.35-11.0), respectively]. Propensity score adjustment and inverse probability weighing yielded similar results. Mediation analysis showed that a higher incidence of anastomotic leakage in patients with c-AKI was primarily mediated by CRP levels (mediation percentage 48%). CONCLUSION: c-AKI after preoperative chemotherapy in esophageal cancer patients was significantly associated with the development of postoperative complications and led to a resultant longer hospital stay. Increased vascular permeability and tissue edema due to prolonged inflammation might explain the mechanisms for the higher incidence of postoperative complications.
Assuntos
Injúria Renal Aguda , Neoplasias Esofágicas , Humanos , Cisplatino/efeitos adversos , Estudos Retrospectivos , Fístula Anastomótica , Fatores de Risco , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/cirurgia , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/epidemiologia , IncidênciaRESUMO
An-81-year-old man presented to another doctor complaining of epigastric pain. He was referred to us after the laboratory data revealed a high serum CEA and abdominal ultrasonography showed the space occupying lesion in the left liver. Abdominal CT revealed advanced gallbladder cancer infiltrating the liver and colon and found annular pancreas surrounding the descending portion of duodenum. We chose partial hepatectomy(S4a+S5), extrahepatic bile duct resection with hepaticojejunostomy and partial colectomy. Pathological diagnosis of the tumor was pT3N1M0, gallbladder cancer. The patient was discharged on the 21 days after operation. The frequency of malignant tumors in adult annular pancreas are not revealed. But some cases present with adult annular pancreas complicating the biliary tract tumor. We experienced a case of advanced gallbladder cancer with adult annular pancreas and report our case and review the pertinent literature.
Assuntos
Neoplasias da Vesícula Biliar , Pancreatopatias , Masculino , Humanos , Adulto , Neoplasias da Vesícula Biliar/patologia , Pâncreas/patologia , Pancreatopatias/cirurgia , Fígado/patologiaRESUMO
A 35-year-old man who had fever and stomachache was referred to our hospital. He underwent surgery and chemoradiotherapy for neuroblastoma as a child and subsequently developed leukemia. Frequent blood transfusions and bone marrow transplants were performed due to anemia. Abdominal contrast CT scan and contrast MRI showed tumorous lesions with a diameter of 60×42 mm in liver S6, and a tendency to increase in a short term. There was also hemochromatosis in the liver. We considered it a malignant tumor and performed a right lobectomy. Pathological examination diagnosed the tumor hepatic angiosarcoma. The postoperative course was fine and he was discharged without complications. But multiple liver metastases appeared 6 months after surgery. We performed chemotherapy but he passed away 10 months after surgery. Hepatic angiosarcoma is a rare disease among liver malignancies and has a very poor prognosis. As for the cause of hepatic angiosarcoma, many of them are unknown, but chronic exposures such as vinyl monomers have been reported in some cases. Hemochromatosis has been reported as a background factor for malignant tumors such as hepatocellular carcinoma. In this case it is possible that it contributed to the development of hepatic angiosarcoma.
Assuntos
Carcinoma Hepatocelular , Hemangiossarcoma , Hemocromatose , Neoplasias Hepáticas , Masculino , Criança , Humanos , Adulto , Hemocromatose/complicações , Hemangiossarcoma/cirurgia , Neoplasias Hepáticas/cirurgia , Carcinoma Hepatocelular/complicaçõesRESUMO
The patient described herein was diagnosed with left breast, endometrial, and early gastric cancers at 49, 53, and 57 years of age, respectively. Magnetic resonance cholangiopancreatography performed when she was undergoing treatment for cholecystitis at 50 years of age showed local pancreatic duct dilatation in the pancreatic head. She was followed in the Department of Gastroenterology at our hospital for an intraductal papillary mucinous neoplasm(IPMN). An abdominal computed tomography scan obtained at 59 years of age revealed dilation of the main pancreatic duct in the pancreas body and tail, therefore an endoscopic ultrasound-guided fine needle aspiration was performed. She was diagnosed with pancreatic cancer and underwent a laparoscopic distal pancreatectomy. The postoperative course was uneventful; however, the pancreatic cancer recurred and she died approximately 14 months postoperatively. Reports of multiple cancers associated with IPMNs are rare, yet we managed a patient with a pancreatic head IPMN complicated by metachronous quadruple carcinomas( breast, endometrial, gastric, and pancreatic cancers).
Assuntos
Adenocarcinoma Mucinoso , Carcinoma Ductal Pancreático , Neoplasias Intraductais Pancreáticas , Neoplasias Pancreáticas , Feminino , Humanos , Carcinoma Ductal Pancreático/patologia , Neoplasias Intraductais Pancreáticas/cirurgia , Pancreatectomia , Adenocarcinoma Mucinoso/cirurgia , Adenocarcinoma Mucinoso/diagnóstico , Recidiva Local de Neoplasia/cirurgia , Neoplasias Pancreáticas/patologia , Ductos Pancreáticos/patologiaRESUMO
Chemotherapy is the standard therapy for unresectable intrahepatic cholangiocarcinoma(ICC), but chemotherapy is not efficacious. Proton beam therapy(PBT)has been covered by Japanese health insurance for ICC since 2022, and the number of cases is expected to increase. In some cases, irradiation is difficult due to the close proximity of the gastrointestinal tract to the tumor. We report our management of a patient with ICC close to the gastrointestinal tract. The patient was a 69-year- old woman with a history of distal gastrectomy and Billroth-â reconstruction for gastric cancer. A CT scan showed a tumor in liver S3; a biopsy revealed ICC. Because the tumor was in contact with the gastroduodenal anastomosis, we placed an absorbable spacer and performed PBT. After the treatment, the tumor shrank slightly. Although the liver is anatomically adjacent to the digestive tract, the placement of absorbable spacers facilitates performing PBT without adverse events, and is thus considered a useful treatment.
Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Terapia com Prótons , Feminino , Humanos , Idoso , Gastroenterostomia , Colangiocarcinoma/radioterapia , Colangiocarcinoma/cirurgia , Colangiocarcinoma/patologia , Ductos Biliares Intra-Hepáticos/patologia , Neoplasias dos Ductos Biliares/radioterapia , Neoplasias dos Ductos Biliares/cirurgia , Neoplasias dos Ductos Biliares/patologiaRESUMO
The Hippo signaling pathway is involved in the pathophysiology of various cardiovascular diseases. Yes-associated protein (YAP) and transcriptional enhancer activator domain (TEAD) transcriptional factors, the main transcriptional complex of the Hippo pathway, were recently identified as modulators of phenotypic switching of vascular smooth muscle cells (VSMCs). However, the intrinsic regulator of YAP/TEAD-mediated gene expressions involved in vascular pathophysiology remains to be elucidated. Here, we identified Homeobox A4 (HOXA4) as a potent repressor of YAP/TEAD transcriptional activity using lentiviral shRNA screen. Mechanistically, HOXA4 interacts with TEADs and attenuates YAP/TEAD-mediated transcription by competing with YAP for TEAD binding. We also clarified that the expression of HOXA4 is relatively abundant in the vasculature, especially in VSMCs. In vitro experiments in human VSMCs showed HOXA4 maintains the differentiation state of VSMCs via inhibition of YAP/TEAD-induced phenotypic switching. We generated Hoxa4-deficient mice and confirmed the downregulation of smooth muscle-specific contractile genes and the exacerbation of vascular remodeling after carotid artery ligation in vivo. Our results demonstrate that HOXA4 is a repressor of VSMC phenotypic switching by inhibiting YAP/TEAD-mediated transcription.
Assuntos
Genes Homeobox , Proteínas de Homeodomínio/genética , Fatores de Transcrição/genética , Remodelação Vascular , Animais , Camundongos , Miócitos de Músculo Liso , Transdução de SinaisRESUMO
BACKGROUND: There is scarce data evaluating the current practice pattern and clinical outcomes for patients with severe aortic stenosis (AS), including both those who underwent surgical aortic valve replacement (SAVR) or transcatheter aortic valve implantation (TAVI) and those who were managed conservatively in the TAVI era.MethodsâandâResults: The Contemporary outcomes after sURgery and medical tREatmeNT in patients with severe Aortic Stenosis (CURRENT AS) Registry-2 is a prospective, physician-initiated, multicenter registry enrolling consecutive patients who were diagnosed with severe AS between April 2018 and December 2020 among 21 centers in Japan. The rationale for the prospective enrollment was to standardize the assessment of symptomatic status, echocardiographic evaluation, and other recommended diagnostic examinations such as computed tomography and measurement of B-type natriuretic peptide. Moreover, the schedule of clinical and echocardiographic follow up was prospectively defined and strongly recommended for patients who were managed conservatively. The entire study population consisted of 3,394 patients (mean age: 81.6 years and women: 60%). Etiology of AS was degenerative in 90% of patients. AS-related symptoms were present in 60% of patients; these were most often heart failure symptoms. The prevalence of high- and low-gradient AS was 58% and 42%, respectively, with classical and paradoxical low-flow low-gradient AS in 4.6% and 6.7%, respectively. CONCLUSIONS: The CURRENT AS Registry-2 might be large and meticulous enough to determine the appropriate timing of intervention for patients with severe AS in contemporary clinical practice.
Assuntos
Estenose da Valva Aórtica , Implante de Prótese de Valva Cardíaca , Substituição da Valva Aórtica Transcateter , Idoso de 80 Anos ou mais , Feminino , Humanos , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/cirurgia , Implante de Prótese de Valva Cardíaca/efeitos adversos , Peptídeo Natriurético Encefálico , Estudos Prospectivos , Sistema de Registros , Fatores de Risco , Índice de Gravidade de Doença , Substituição da Valva Aórtica Transcateter/efeitos adversos , Resultado do Tratamento , MasculinoRESUMO
PURPOSE: To evaluate the blood flow at the site of delta-shaped anastomosis during robotic distal gastrectomy and determine surgical outcomes and risk factors for ischemia at the anastomotic site from the perspective of clinical characteristics, surgical outcomes and perigastric vascular anatomy. METHODS: We included 55 patients who underwent robotic distal gastrectomy with a blood flow evaluation in the duodenal walls using intravenous indocyanine green injection with the da Vinci Xi-equipped Firefly system. Additional resection was performed in patients with a poor blood flow. Clinical characteristics, surgical outcomes and perigastric vascular anatomy were compared between the 45 patients with sufficient blood flow (group S) and the 10 patients with insufficient blood flow (group I). Vascular anatomy was assessed by preoperative contrast-enhanced computed tomography according to Hiatt's classification. RESULTS: The patient characteristics and surgical outcomes were not significantly different. No patient developed anastomotic complications requiring intervention; more patients in group I had aberrant branching of the left hepatic artery than those in group S (p = 0.047). CONCLUSIONS: An indocyanine green-based blood flow evaluation might be an effective method of preventing anastomotic complications of delta-shaped anastomosis. Anatomical branching variations of the left hepatic artery might be a risk factor for impaired vascular perfusion of the anastomotic site.
Assuntos
Verde de Indocianina , Procedimentos Cirúrgicos Robóticos , Anastomose Cirúrgica/métodos , Fístula Anastomótica/etiologia , Fístula Anastomótica/prevenção & controle , Fluorescência , Gastrectomia/métodos , HumanosRESUMO
BACKGROUND: In gastrectomies, especially subtotal gastrectomies and operations on the gastroesophageal junction, identifying the exact location of the tumor and establishing the appropriate resection line is very important. Accurate resection lines have a major impact on the preservation of organ function and curability. Preservation of as much as possible of the remaining stomach, including the fornix, may be an important surgical goal for maintaining an adequate postoperative quality of life. In adenocarcinoma of the gastroesophageal junction, the height of the esophageal dissection may affect reconstruction of the transhiatal approach. METHODS: We perform a new technique, near infrared ray-guided surgery, for the accurate localization of a tumor using the Firefly technology of the daVinci Xi system and intra-operative upper gastrointestinal endoscopy. We used this new technique for cases of upper gastric cancer or adenocarcinoma of the gastroesophageal junction. In this retrospective study, we examined to determine the extent (mm) of the tumor invasion of the esophagus, visualization of near infrared ray contained within endoscopic light, and distance from the proximal margin of the tumor to the surgical cut line on rapid histopathology and in the permanent preparation, including the operative videos and extracted specimens. RESULTS: We performed near infrared ray-guided surgery for 12 patients with gastric cancer or adenocarcinoma of the gastroesophageal junction, and the near infrared ray was clearly seen as green light with Firefly mode in all the patients. Near infrared ray-guided surgery was useful for obtaining localization of the tumor. In addition, it was possible to resect organ with adequate margins from tumor. Rapid intraoperative histopathological examinations confirmed that the resected specimens had negative margins. None of the patients required additional resection. CONCLUSIONS: We believe that because near infrared ray-guided surgery can provide an accurate resection line, it will be useful for the resection of upper gastric cancer and adenocarcinoma of the gastroesophageal junction. It will also provide patients with a good postoperative quality of life after surgery.
Assuntos
Adenocarcinoma , Neoplasias Esofágicas , Neoplasias Gástricas , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Animais , Neoplasias Esofágicas/diagnóstico por imagem , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Junção Esofagogástrica/patologia , Junção Esofagogástrica/cirurgia , Vaga-Lumes , Gastrectomia/métodos , Gastroscopia , Humanos , Raios Infravermelhos , Margens de Excisão , Qualidade de Vida , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , TecnologiaRESUMO
ß-1,3-d-Glucan is a ubiquitous glucose polymer produced by plants, bacteria, and most fungi. It has been used as a diagnostic tool in patients with invasive mycoses via a highly-sensitive reagent consisting of the blood coagulation system of horseshoe crab. However, no method is currently available for measuring ß-1,6-glucan, another primary ß-glucan structure of fungal polysaccharides. Herein, we describe the development of an economical and highly-sensitive and specific assay for ß-1,6-glucan using a modified recombinant endo-ß-1,6-glucanase having diminished glucan hydrolase activity. The purified ß-1,6-glucanase derivative bound to the ß-1,6-glucan pustulan with a KD of 16.4 nm We validated the specificity of this ß-1,6-glucan probe by demonstrating its ability to detect cell wall ß-1,6-glucan from both yeast and hyphal forms of the opportunistic fungal pathogen Candida albicans, without any detectable binding to glucan lacking the long ß-1,6-glucan branch. We developed a sandwich ELISA-like assay with a low limit of quantification for pustulan (1.5 pg/ml), and we successfully employed this assay in the quantification of extracellular ß-1,6-glucan released by >250 patient-derived strains of different Candida species (including Candida auris) in culture supernatant in vitro We also used this assay to measure ß-1,6-glucan in vivo in the serum and in several organs in a mouse model of systemic candidiasis. Our work describes a reliable method for ß-1,6-glucan detection, which may prove useful for the diagnosis of invasive fungal infections.
Assuntos
Técnicas Biossensoriais/métodos , Polissacarídeos Fúngicos/química , Glicosídeo Hidrolases/metabolismo , Polissacarídeos/análise , beta-Glucanas/análise , Animais , Candida/metabolismo , Ensaios Enzimáticos/métodos , Feminino , Polissacarídeos Fúngicos/metabolismo , Glicosídeo Hidrolases/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Polissacarídeos/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , beta-Glucanas/metabolismoRESUMO
Due to the COVID-19 pandemic, the 84thAnnual Meeting of the Japanese Circulation Society (JCS) was held in a web-based format for the first time in its history as "The Week for JCS 2020" from Monday, July 27 to Sunday, August 2, 2020. All sessions, including general abstracts, were streamed live or on-demand. The main theme of the meeting was "Change Practice!" and the aim was to organize the latest findings in the field of cardiovascular medicine and discuss how to change practice. The total number of registered attendees was over 16,800, far exceeding our expectations, and many of the sessions were viewed by far more people than at conventional face-to-face scientific meetings. At this conference, the power of online information dissemination was fully demonstrated, and the evolution of online academic meetings will be a direction that cannot be reversed in the future. The meeting was completed with great success, and we express our heartfelt gratitude to all affiliates for their enormous amount of work, cooperation, and support.
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Cardiologia/organização & administração , Congressos como Assunto/organização & administração , Sociedades Científicas/organização & administração , Telecomunicações/organização & administração , Cardiologia/tendências , Doenças Cardiovasculares/diagnóstico por imagem , Doenças Cardiovasculares/terapia , Congressos como Assunto/estatística & dados numéricos , Congressos como Assunto/tendências , Humanos , Japão , Pesquisa , Inquéritos e Questionários , Telecomunicações/estatística & dados numéricos , Telecomunicações/tendênciasRESUMO
PURPOSE: One of the complications in laparoscopic surgery is port-site hernia. It is a rare but potentially dangerous complication. Especially when using ports with a size 10 mm or more, it is required to securely close the port site. However, this procedure is often difficult especially for obese patients. METHODS: We herein devised a new closure method by using a device developed for port site. These techniques are methods that can close the port site by a combination of putting in and out of thread and port rotation without removing a port. The port-site closure with these techniques was done for 53 port sites of 41 patients. RESULTS: The port site was closed horizontally or vertically, depending on the shape of the port site for two patients. Modified Z-suture was done for other 37 patients. To date, we have not noted any complications from this new method, including port-site hernia. CONCLUSION: With our technique, we could save operation time and reduce stress of us especially for obese patients. We would like to increase the number of patients and verify the safety and usefulness in further study.
Assuntos
Laparoscopia , Humanos , Duração da Cirurgia , Complicações Pós-Operatórias , SuturasRESUMO
Chitooligosaccharides exhibit several biomedical activities, such as inflammation and tumorigenesis reduction in mammals. The mechanism of the chitooligosaccharides' formation in vivo has been, however, poorly understood. Here we report that mouse acidic chitinase (Chia), which is widely expressed in mouse tissues, can produce chitooligosaccharides from deacetylated chitin (chitosan) at pH levels corresponding to stomach and lung tissues. Chia degraded chitin to produce N-acetyl-d-glucosamine (GlcNAc) dimers. The block-type chitosan (heterogenous deacetylation) is soluble at pH 2.0 (optimal condition for mouse Chia) and was degraded into chitooligosaccharides with various sizes ranging from di- to nonamers. The random-type chitosan (homogenous deacetylation) is soluble in water that enables us to examine its degradation at pH 2.0, 5.0, and 7.0. Incubation of these substrates with Chia resulted in the more efficient production of chitooligosaccharides with more variable sizes was from random-type chitosan than from the block-type form of the molecule. The data presented here indicate that Chia digests chitosan acquired by homogenous deacetylation of chitin in vitro and in vivo. The degradation products may then influence different physiological or pathological processes. Our results also suggest that bioactive chitooligosaccharides can be obtained conveniently using homogenously deacetylated chitosan and Chia for various biomedical applications.
Assuntos
Quitinases/metabolismo , Quitosana/metabolismo , Concentração de Íons de Hidrogênio , Pulmão/metabolismo , Oligossacarídeos/metabolismo , Estômago/metabolismo , Animais , Quitinases/química , Quitosana/química , Hidrólise , Camundongos , Oligossacarídeos/química , Especificidade de Órgãos , Especificidade por Substrato , Difração de Raios XRESUMO
To obtain high quality of drinking water free from biocontaminants is especially important issue. A new strategy employing smectic liquid-crystalline ionic membranes exhibiting 2D structures of layered nanochannels for water treatment is proposed for efficient virus removal and sufficient water flux. The smectic A (SmA) liquid-crystalline membranes obtained by in situ polymerization of an ionic mesogenic monomer are examined for removal of three distinct viruses with small size: Qß bacteriophage, MS2 bacteriophage, and Aichi virus. The semi-bilayer structure of the SmA significantly obstructs the virus penetration with an average log reduction value of 7.3 log10 or the equivalent of reducing 18 million viruses down to 1. Furthermore, the layered nanochannels of the SmA liquid crystal allow efficient water permeation compared to other types of liquid-crystalline membrane consisting of nanopores.
Assuntos
Cristais Líquidos , Nanoestruturas , Vírus , Purificação da Água , Membranas ArtificiaisRESUMO
Di-N-acetylchitobiase (Ctbs) degrades ß-1,4 glycoside bonds of the chitobiose core of free asparagine-linked glycan. This study examined whether Ctbs degrades chitin-oligosaccharides to GlcNAc in mammals. We analyzed Ctbs mRNA and protein expression in mouse tissues and characterized enzymatic activity using recombinant mouse Ctbs expressed in Escherichia coli. Ctbs mRNA and protein were expressed in various tissues of mouse, including the stomach. Optimal conditions for recombinant Ctbs were pH 3.0 and 45°C, and the recombinant enzyme was retained more than 94% activity after incubation at pH 3.0-7.0 and below 37°C. The recombinant Ctbs hydrolyzed (GlcNAc)3 and (GlcNAc)6 at pH 3.0 and produced GlcNAc. The K m of Ctbs was lowest with (GlcNAc)3 as a substrate. k cat/K m was fourfold as high with (GlcNAc)3 and (GlcNAc)4 as substrates than with (GlcNAc)2. These results suggest that Ctbs digests chitin-oligosaccharides or (GlcNAc)2 of reducing-end residues of oligosaccharides and produces GlcNAc in mouse tissues.