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Heterocyclic aryl selenides have recently attracted considerable research interest owing to their applications in biological and pharmaceutical fields. Herein, we describe a simple and general synthesis of 3-selanylindoles via a novel regioselective C-H selenation of indoles using a bismuth reagent as a catalyst. The reactions of indoles with diselenides in the presence of 10 mol% BiI3 at 100 °C in DMF afforded the corresponding 3-selanylindoles in moderate-to-excellent yields. The reaction proceeded efficiently under aerobic conditions by adding only a catalytic amount of BiI3, which was non-hygroscopic and less toxic, and both selanyl groups of the diselenide were transferred to the desired products.
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G protein-coupled receptor (GPR) 120 is expressed in enteroendocrine cells secreting glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide/gastric inhibitory polypeptide (GIP), and cholecystokinin (CCK). Although GPR120 signaling in adipose tissue and macrophages has been reported to ameliorate obesity and insulin resistance in a high long-chain triglyceride (LCT) diet, intestine-specific roles of GPR120 are unclear. To clarify the metabolic effect of GPR120 in the intestine, we generated intestine-specific GPR120-knockout (GPR120int-/-) mice. In comparison with floxed GPR120 (WT) mice, GPR120int-/- mice exhibited reduced GIP secretion and CCK action without change of insulin, GLP-1, or peptide YY (PYY) secretion after a single administration of LCT. Under a high-LCT diet, GPR120int-/- mice showed a mild reduction of body weight and substantial amelioration of insulin resistance and fatty liver. Moreover, liver and white adipose tissue (WAT) of GPR120int-/-mice exhibited increased Akt phosphorylation and reduced gene expression of suppressor of cytokine signaling (SOCS) 3, which inhibits insulin signaling. In addition, gene expression of inflammatory cytokines in WAT and lipogenic molecules in liver were reduced in GPR120int-/- mice. These findings suggest that inhibition of GPR120 signaling in intestine ameliorates insulin resistance and fatty liver under high-LCT diet feeding.NEW & NOTEWORTHY We generated novel intestine-specific GPR120-knockout (GPR120int-/-) mice and investigated the metabolic effect of GPR120 in the intestine. GPR120int-/- mice exhibited a reduction of GIP secretion and CCK action after a single administration of LCT. Under a high-LCT diet, GPR120int-/- mice showed mild improvement in obesity and marked amelioration of insulin resistance and hepatic steatosis. Our results indicate an important role of intestinal GPR120 on insulin resistance and hepatic steatosis.
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Dieta Hiperlipídica , Intestinos , Receptores Acoplados a Proteínas G , Transdução de Sinais , Animais , Camundongos , Camundongos Endogâmicos C57BL , Intestinos/metabolismo , Resistência à Insulina , Triglicerídeos/administração & dosagem , Fígado Gorduroso/metabolismo , Camundongos Knockout , Glucose/administração & dosagem , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Obesidade/metabolismo , Óleo de Milho/administração & dosagemRESUMO
Under hypoxia, Saccharomyces cerevisiae forms cytoplasmic condensates composed of proteins, including glycolytic enzymes, that are thought to regulate cellular metabolism. However, the hypoxic conditions required for condensate formation remain unclear. In this study, we developed a 300-mL-scale culture method to produce condensate-forming cells by precisely controlling the dissolved oxygen (DO) level in the media. Using enolase as a model, a foci formation rate of more than 50% was achieved at â¼0.1% DO, and the results showed that the DO level affected the foci formation rate. The foci formation rates of the previously reported foci-deficient strains and strains with single amino acid substitutions in the endogenous enolase were examined, and the effect of these amino acid substitutions on glucose consumption and ethanol and glycerol production under hypoxia was evaluated. The results of this study contribute to the investigation of the mechanisms that regulate biomacromolecular condensates under hypoxia.
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Oxigênio , Saccharomyces cerevisiae , Humanos , Saccharomyces cerevisiae/genética , Hipóxia , Fosfopiruvato Hidratase , GlicerolRESUMO
PURPOSE: To clarify the influence of additional internal iliac artery (IIA) resection on the loss of the gluteus muscle volume after pelvic exenteration (PE). METHODS: The subjects of this retrospective analysis were 78 patients who underwent PE with or without IIA resection (n = 44 and n = 34, respectively) between 2006 and 2018. The areas of gluteal muscles (GMs) and psoas muscles (PSMs) were calculated using CT images before and 6 months after PE, and the difference was compared. RESULTS: The volumes of the GMs and PSMs were significantly reduced after PE (P < 0.001 and P = 0.005, respectively). In the IIA resection group, the GMs were significantly reduced after surgery, but the PSMs were not. The maximum GM (Gmax) was the most atrophied among the GMs. Multivariable analysis revealed that complete IIA resection was an independent promotor of the loss of volume of the Gmax (P = 0.044). In 18 patients with unilateral IIA resection, the downsizing rate of the Gmax was significantly greater on the resected side than on the non-resected side (P = 0.008). CONCLUSIONS: The GMs and PSMs were significantly smaller after PE. Complete IIA resection reduced the Gmax area remarkably. Preservation of the superior gluteus artery is likely to help maintain Gmax size, suggesting a potential preventative measure against secondary sarcopenia.
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Implante de Prótese Vascular , Exenteração Pélvica , Humanos , Artéria Ilíaca/cirurgia , Exenteração Pélvica/métodos , Estudos Retrospectivos , Implante de Prótese Vascular/métodos , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/cirurgiaRESUMO
Transanal total mesorectal excision (taTME) has been rapidly accepted as a promising surgical approach to the distal rectum. The benefits include ease of access to the bottom of the deep pelvis linearly over a short distance in order to easily visualize the important anatomy. Furthermore, the distal resection margins can be secured under direct vision. Additionally, a two-team approach combining taTME with a transabdominal approach could decrease the operative time and conversion rate. Although taTME was expected to become more rapidly popularized worldwide, enthusiasm for it has stalled due to unfamiliar intraoperative complications, a lack of oncologic evidence from randomized trials, and the widespread use of robotic surgery. While international registries have reported favorable short- and medium-term outcomes from taTME, a Norwegian national study reported a high local recurrence rate of 9.5%. The characteristics of the recurrences included rapid, multifocal growth in the pelvis, which was quite different from recurrences following traditional transabdominal TME; thus, the Norwegian Colorectal Cancer Group reached a consensus for a temporary moratorium on the performance of taTME. To ensure acceptable baseline quality and patient safety, taTME should be performed by well-trained colorectal surgeons. Although the appropriate indications for taTME remain controversial, the transanal approach is extremely important as a means of goal setting in difficult TME cases and as an aid to the transabdominal approach in various types of extended pelvic surgeries. The benefits in transanal lateral lymph node dissection and pelvic exenteration are presented herein.
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Laparoscopia , Neoplasias Retais , Cirurgia Endoscópica Transanal , Humanos , Cirurgia Endoscópica Transanal/efeitos adversos , Neoplasias Retais/cirurgia , Reto/cirurgia , Pelve , Recidiva , Resultado do Tratamento , Complicações Pós-Operatórias/etiologiaRESUMO
BACKGROUND: Although surgical resection for liver or lung metastases of colorectal cancer has been widely accepted, the use of this approach for extrahepatopulmonary metastases remains debatable due to the systemic nature of the disease. The aim of this study was to clarify the utility of resection along with perioperative chemotherapy for patients with extrahepatopulmonary metastases of colon cancer. METHODS: This is a retrospective single-arm study at a single institution. Forty-two patients with resectable extrahepatopulmonary metastases who underwent metastasectomy with curative intent between 2009 and 2018 at Nagoya University Hospital were retrospectively analyzed. The primary outcomes measured were overall and relapse-free survival. RESULTS: The most common metastatic site was the peritoneum (n = 31), followed by the distant lymph nodes (n = 10), ovary (n = 1) and spleen (n = 1), with overlaps. Preoperative and postoperative chemotherapies were administered to 22 and 8 patients, respectively; the remaining 14 patients received surgery alone. R0 resection was achieved in 36 patients (85.7%). The 5-year overall survival and 3-year relapse-free survival rates were 58.6% and 33.8%, respectively. In the univariate analysis, R1 resection was associated with a poor relapse-free survival rate (P = 0.02). In the multivariate analysis, the absence of perioperative chemotherapy was an independent risk factor for poor overall survival rates (P = 0.02). CONCLUSIONS: Surgical resection benefited selected patients with extrahepatopulmonary metastases with favorable long-term survival outcomes. Surgery alone without systemic chemotherapy is likely to bring poor outcome; therefore, preoperative induction might be promising to keep up with chemotherapy.
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Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Hepáticas , Metastasectomia , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Neoplasias do Colo/cirurgia , Neoplasias Colorretais/patologia , Feminino , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
PURPOSE: Parastomal hernia (PH) develops more frequently than incisional hernia (IH) after colorectal surgery with stoma. This study evaluated our hypothesis that inward traction of the fascia when closing a midline incision widens the stoma hole and increases the incidence of PH. METHODS: A total of 795 patients who underwent colorectal resection between 2006 and 2016 were retrospectively analyzed. The risk classification was constructed from IH risk factors extracted from the non-stoma group. Then, the classification was extrapolated to the stoma group for predicting midline IH and PH. RESULTS: The incidence of IH was 5.3% in the stoma group and 12.5% in the non-stoma group (p = 0.005). PH developed in 19.6% of 97 patients with permanent stoma. The risk classification was able to predict PH without a significant difference but was well balanced in patients with permanent stoma; however, it failed to predict IH in the stoma group. CONCLUSION: The risk classification constructed from the non-stoma group was useful for predicting not midline IH but PH, suggesting that the stoma site was the most vulnerable for herniation. The "fighting over the fascia" theory between the midline incision and stoma hole may explain the causal relationship between the midline IH and PH.
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Cirurgia Colorretal , Hérnia Incisional , Ferida Cirúrgica , Colectomia/efeitos adversos , Fáscia , Humanos , Incidência , Hérnia Incisional/epidemiologia , Hérnia Incisional/etiologia , Estudos Retrospectivos , Fatores de RiscoRESUMO
The diagnosis of the dynamics, accumulation, and engraftment of transplanted stem cells in vivo is essential for ensuring the safety and the maximum therapeutic effect of regenerative medicine. However, in vivo imaging technologies for detecting transplanted stem cells are not sufficient at present. We developed nanohybrid particles composed of dendron-baring lipids having two unsaturated bonds (DLU2) molecules, quantum dots (QDs), and magnetic nanoparticles in order to diagnose the dynamics, accumulation, and engraftment of transplanted stem cells, and then addressed the labeling and in vivo fluorescence and magnetic resonance (MR) imaging of stem cells using the nanohybrid particles (DLU2-NPs). Five kinds of DLU2-NPs (DLU2-NPs-1-5) composed of different concentrations of DLU2 molecules, QDs525, QDs605, QDs705, and ATDM were prepared. Adipose tissue-derived stem cells (ASCs) were labeled with DLU2-NPs for 4 h incubation, no cytotoxicity or marked effect on the proliferation ability was observed in ASCs labeled with DLU2-NPs (640- or 320-fold diluted). ASCs labeled with DLU2-NPs (640-fold diluted) were transplanted subcutaneously onto the backs of mice, and the labeled ASCs could be imaged with good contrast using in vivo fluorescence and an MR imaging system. DLU2-NPs may be useful for in vivo multimodal imaging of transplanted stem cells.
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Nanopartículas de Magnetita , Pontos Quânticos , Animais , Imageamento por Ressonância Magnética , Nanopartículas de Magnetita/toxicidade , Camundongos , Imagem Multimodal , Pontos Quânticos/química , Células-TroncoRESUMO
The development of novel and efficient synthesis methods for 2-substituted benzazole derivatives is of interest as they are biologically active substances. Herein, a simple method for the synthesis of 2-aryl- and 2-alkyl-substituted benzazoles is described. The reaction of 2-aminophenols with thioamides at 60 °C in the presence of triphenylbismuth dichloride in 1,2-dichloroethane as a promoter afforded various 2-aryl- and 2-alkylbenzoxazoles in moderate to excellent yields under mild reaction conditions. This method could also be applied to the synthesis of benzimidazoles and benzothiazoles. This study presents the first use of triphenylbismuth dichloride to produce benzimidoyl chloride from thioamides by desulfurization and chlorination, as well as its application to the synthesis of 2-substituted benzazoles.
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Alkynyl selenides have attracted considerable research interest recently, owing to their applications in the biological and pharmaceutical fields. The Cu-catalyzed tandem reaction for the synthesis of novel alkynyl imidazopyridinyl selenides is presented. A one-pot synthesis route afforded alkynyl imidazopyridinyl selenides in moderate to good yields. This was achieved by a two-step reaction between terminal alkynes and diimidazopyridinyl diselenides, generated from imidazo[1,2-a]pyridines and Se powder, using 10 mol % of CuI and 1,10-phenanthroline as the catalytic system under aerobic conditions. The C(sp2)-Se and C(sp)-Se bond-formation reaction can be performed in one-pot by using inexpensive and easy to handle Se powder as the Se source. The reaction proceeded with terminal alkynes having various substitutions, such as aryl, vinyl, and alkyl groups. The obtained alkynyl imidazopyridinyl selenide was found to undergo nucleophilic substitution reaction on Se atom using organolithium reagents and 1,3-dipolar azide-alkyne cycloaddition based on the alkyne moiety.
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BACKGROUND: The carcinoembryonic antigen (CEA) "value" itself is often useless in patients with a normal CEA level at initial presentation and those with tumor-irrelevant elevated CEA. Although the unified marker using CEA has been desirable for recurrent tumor staging as well as for primary tumor staging, little is known concerning its relationship with the survival of patients with recurrent colorectal cancer in particular. METHODS: This retrospective historical study included patients who experienced disease relapse after curative surgery for stage I-III colorectal cancer between 2006 and 2018. A total of 129 patients with recurrent disease after curative surgery for colorectal cancer were included. We focused on the CEA "ratio" (CEA-R: the ratio of the CEA level at the time of recurrence to that measured 3 months before recurrence) and aimed to evaluate the correlation between CEA-R and survival in recurrent colorectal cancer. RESULTS: Patients with a high CEA-R (≥ 2) exhibited significantly worse 2 year survival than those with a low CEA-R (< 2) (88.1% vs. 44.9%, P < 0.001), irrespective of the CEA value before primary resection. Multivariate analyses demonstrated that the CEA-R (HR; 3.270, 95% CI 1.646-6.497, P = 0.001) was a significant prognostic factor. CONCLUSION: The CEA-R is a potential marker stratifying the survival of patients with disease relapse who exhibit aggressive biology at recurrent disease foci. As a novel marker, the CEA-R would serve as a clinical guide for tailoring treatment strategies at the time of disease relapse in patients with colorectal cancer.
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Antígeno Carcinoembrionário , Neoplasias Colorretais , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Seguimentos , Humanos , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Prognóstico , Estudos RetrospectivosRESUMO
The expectation that antimony (Sb) compounds should display phosphorescence emissions based on the "heavy element effect" prompted our interest in the introduction of antimony to a biaryl as the bridging atom in a fused heterole system. Herein, the synthesis, molecular structures, and optical properties of novel benzene-fused heteroacenes containing antimony or arsenic atoms are described. The stiboles and arsole were prepared by the condensation of dibromo(phenyl)stibane or dichloro(phenyl)arsine with dilithium intermediates derived from the corresponding dibromo compounds. Nuclear magnetic resonance (NMR) spectroscopy and X-ray crystal analysis revealed that the linear pentacyclic stibole was highly symmetric in both the solution and crystal states. In contrast, the curved pentacyclic stibole adopted a helical structure in solution, and surprisingly, only M helical molecules were crystallized from the racemate. All synthesized compounds produced very weak or no emissions at room temperature or in the solid state. In contrast, the linear penta- and tetracyclic stiboles exhibited clear phosphorescence emissions in the CHCl3 frozen matrix at 77 K under aerobic conditions.
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Arsênio/química , Benzeno/química , Compostos Heterocíclicos/química , Hidrocarbonetos Bromados/química , Cristalografia por Raios X , Luminescência , Modelos Moleculares , Estrutura MolecularRESUMO
Phosphole-fused π-conjugated acenes have been attracting interest because of the attractive features of the phosphole moiety, such as fluorescence and chemically modifiable properties. Herein, 6-phenyl-6H-benzo[f]naphtho[2,3-b]phosphoindole was prepared by reacting dichlorophenylphosphine with a dilithium intermediate derived from 3,3'-dibromo-2,2'-binaphthyl. Various derivatives, such as a phospholium salt and a borane-phosphole complex with functional groups on the phosphorus atom were synthesized using the obtained phosphole as a common starting material. Single-crystal X-ray analysis of the parent benzo[f]naphtho[2,3-b]phosphoindole revealed that the pentacyclic ring is almost planar. Fluorescence spectroscopy data showed that the phosphole derivatives, such as phosphine oxide and the phospholium salt and borane complex exhibited photoluminescence in chloroform.
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Acute myocardial infarction is a leading cause of death among single organ diseases. Despite successful reperfusion therapy, ischaemia reperfusion injury (IRI) can induce oxidative stress (OS), cardiomyocyte apoptosis, autophagy and release of inflammatory cytokines, resulting in increased infarct size. In IRI, mitochondrial dysfunction is a key factor, which involves the production of reactive oxygen species, activation of inflammatory signalling cascades or innate immune responses, and apoptosis. Therefore, intercellular mitochondrial transfer could be considered as a promising treatment strategy for ischaemic heart disease. However, low transfer efficiency is a challenge in clinical settings. We previously reported uptake of isolated exogenous mitochondria into cultured cells through co-incubation, mediated by macropinocytosis. Here, we report the use of transactivator of transcription dextran complexes (TAT-dextran) to enhance cellular uptake of exogenous mitochondria and improve the protective effect of mitochondrial replenishment in neonatal rat cardiomyocytes (NRCMs) against OS. TAT-dextran-modified mitochondria (TAT-Mito) showed a significantly higher level of cellular uptake. Mitochondrial transfer into NRCMs resulted in anti-apoptotic capability and prevented the suppression of oxidative phosphorylation in mitochondria after OS. Furthermore, TAT-Mito significantly reduced the apoptotic rates of cardiomyocytes after OS, compared to simple mitochondrial transfer. These results indicate the potential of mitochondrial replenishment therapy in OS-induced myocardial IRI.
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Dextranos/química , Mitocôndrias/metabolismo , Miócitos Cardíacos/citologia , Transativadores/genética , Útero/metabolismo , Animais , Animais Recém-Nascidos , Apoptose , Células Cultivadas , Técnicas de Cocultura , Feminino , Humanos , Imunidade Inata , Técnicas In Vitro , Inflamação , Mitocôndrias Cardíacas/metabolismo , Miócitos Cardíacos/metabolismo , Necroptose , Estresse Oxidativo , Pinocitose , Ratos , Espécies Reativas de Oxigênio , Traumatismo por ReperfusãoRESUMO
A simple general method for the synthesis of nitriles using the inexpensive and easy to handle iodine (I2) is described herein. The reaction of thioamides with I2 in the presence of triethylamine at room temperature under aerobic conditions afforded various nitriles bearing aryl, vinyl, and alkyl groups in good-to-excellent yields. This method was also effective for conversion from thioureas to cyanamides.
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Iodo/química , Nitrilas/síntese química , Tioamidas/química , Estrutura Molecular , Nitrilas/químicaRESUMO
Pd-catalyzed regioselective C-H arylation is a useful tool for the chemical modification of aromatic heterocycles and 2-arylbenzofuran derivatives are of interest as biologically active substances. Herein, the reaction of triarylantimony difluorides with benzofurans under aerobic conditions in 1,2-DCE, using 5 mol% Pd (OAc)2 and 2 eq. of CuCl2 at 80 °C, produced a variety of 2-arylbenzofurans in moderate-to-high yields. The reaction is sensitive to the electronic nature of the substituents on the benzene ring of the triarylantimony difluorides: an electron-donating group showed higher reactivity than an electron-withdrawing group. Single crystal X-ray analysis of tri(p-methylphenyl) antimony difluoride revealed that the central antimony atom exhibits trigonal bipyramidal geometry.
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Benzofuranos/química , Fluoretos/química , Paládio/química , Benzeno/química , Catálise , ElétronsRESUMO
Background and Objectives: The purpose of this systematic review is to synthesize the influence cooling modality has on survival with and without medical complications from exertional heat stroke (EHS) in sport and military populations. Methods and Materials: All peer-reviewed case reports or series involving EHS patients were searched in the following online databases: PubMed, Scopus, SPORTDiscus, Medline, CINAHL, Academic Search Premier, and the Cochrane Library: Central Registry of Clinical Trials. Cooling methods were subdivided into "adequate" (>0.15 °C/min) versus "insufficient" (<0.15 °C/min) based on previously published literature on EHS cooling rates. Results: 613 articles were assessed for quality and inclusion in the review. Thirty-two case reports representing 521 EHS patients met the inclusion criteria. Four hundred ninety-eight (498) patients survived EHS (95.58%) and 23 (4.41%) patients succumbed to complications. Fischer's Exact test on 2 × 2 contingency tables and relative risk ratios were calculated to determine if modality cooling rate was associated with patient outcomes. EHS patients that survived who were cooled with an insufficient cooling rate had a 4.57 times risk of medical complications compared to patients who were treated by adequate cooling methods, regardless of setting (RR = 4.57 (95%CI: 3.42, 6.28)). Conclusions: This is the largest EHS dataset yet compiled that analyzes the influence of cooling rate on patient outcomes. Zero patients died (0/521, 0.00%) when treatment included a modality with an adequate cooling rate. Conversely, 23 patients died (23/521, 4.41%) with insufficient cooling. One hundred seventeen patients (117/521, 22.46%) survived with medical complications when treatment involved an insufficient cooling rate, whereas, only four patients had complications (4/521, 0.77%) despite adequate cooling. Cooling rates >0.15 °C/min for EHS patients were significantly associated with surviving EHS without medical complications. In order to provide the best standard of care for EHS patients, an aggressive cooling rate >0.15 °C/min can maximize survival without medical complications after exercise-induced hyperthermia.