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1.
J Am Chem Soc ; 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38916517

RESUMO

Despite recent advances in porous organic molecular crystals, the engineering of dual-pore systems within the intermolecular voids remains a significant challenge. In this study, we have achieved the crystallization-induced social self-sorting of "quasi-racemic" dialdehydes into a macrocyclic imine. X-ray crystallographic analysis unambiguously characterizes the resulting structure as incorporating two quasi-racemate pairs with four diamine molecules. Notably, different alkyl substituents on the quasi-racemates afford two types of one-dimensional pores within the macrocyclic imine crystal. The different adsorption properties of these pores were substantiated through adsorption experiments. An intriguing helical arrangement of guest molecules was observed within one of the pores. This study provides pioneering evidence that the social self-sorting of quasi-racemates offers a new methodology for creating dual-functional supramolecular materials.

2.
Clin Exp Immunol ; 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38916413

RESUMO

The gut-skin axis has recently been widely recognized, and both the gut and skin have been found to affect each other through a bidirectional connection; however, the precise mechanisms remain to be elucidated. Therefore, we aimed to investigate the effects of chronic skin damage on mouse intestines. Following the chronic skin damage (CSD) model, 4 % sodium dodecyl sulfate (SDS) was applied to the back-shaved murine skin six times for 2 weeks after tape stripping. The small and large intestines were analyzed histologically and immunologically, respectively. Intestinal permeability was measured using fluorescein isothiocyanate-conjugated (FITC)-dextran. The role of IL-13 in the ileum was investigated using an anti-IL-13 antibody. Apoptotic intestinal cells were analyzed using TUNEL staining. Villus atrophy was observed in the small intestine in the CSD model, along with increased permeability. Mast cells, but not T cells, eosinophils, nor ILC-2, were increased in the intestinal mucosa. However, no significant changes were observed in the large intestine. mRNA expression of IL-13 was increased only in the ileum of the CSD model. Apoptotic intestinal epithelial cells were significantly increased in the ileum of the CSD model. Administration of an anti-IL-13 antibody ameliorated the intestinal damage caused by CSD, along with decreased apoptotic cells and mast cell infiltration. Skin damage causes morphological changes in the small intestine, accompanied by increased intestinal permeability, possibly through the IL-13-induced apoptosis of mast cells in the epithelium. Surfactant-mediated mechanical skin damage can cause a leaky gut.

3.
Surg Endosc ; 38(5): 2497-2504, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38466423

RESUMO

INTRODUCTION: Since patients with pharyngeal squamous cell carcinoma (SCC) often have multiple pharyngeal lesions, evaluation of pharyngeal lesions before endoscopic resection (ER) is important. However, detailed endoscopic observation of the entire pharyngeal mucosa under conscious sedation is difficult. We examined the usefulness of endoscopic surveillance with narrow band imaging (NBI) and lugol staining for detection of pharyngeal sublesions during ER for pharyngeal SCC under general anesthesia (endoscopic surveillance during treatment; ESDT). METHODS: From January 2021 through June 2022, we examined 78 patients who were diagnosed with superficial pharyngeal SCC and underwent ER. They underwent the ESDT and for patients who were diagnosed with new lesions of pharyngeal SCC or high-grade dysplasia (HGD) that were not detected in the endoscopic examination before treatment, ER were performed simultaneously for new lesions and the main lesions. The primary endpoint of this study was the detection rate of new lesions of pharyngeal SCC or HGD in the ESDT. RESULTS: Fifteen of the 78 patients were diagnosed as having undetected new pharyngeal lesions in the ESDT and 10 (12.8%) (95% CI 6.9-22.2%) were histopathologically confirmed to have new lesions of pharyngeal SCC or HGD. Among the 13 lesions of SCC or HGD, 8 were found by NBI observation; however, 5 were undetectable using NBI but detectable by lugol staining. All of the 13 lesions had endoscopic findings of pink color sign on lugol staining. CONCLUSIONS: Endoscopic surveillance for pharyngeal sublesions during ER for pharyngeal SCC is feasible and useful.


Assuntos
Neoplasias Faríngeas , Humanos , Masculino , Feminino , Neoplasias Faríngeas/cirurgia , Neoplasias Faríngeas/patologia , Neoplasias Faríngeas/diagnóstico por imagem , Estudos Prospectivos , Idoso , Pessoa de Meia-Idade , Imagem de Banda Estreita/métodos , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/diagnóstico por imagem , Mucosa/patologia , Mucosa/cirurgia , Iodetos , Idoso de 80 Anos ou mais , Ressecção Endoscópica de Mucosa/métodos , Faringe/patologia , Faringe/diagnóstico por imagem
4.
J Infect Chemother ; 30(4): 343-347, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37866623

RESUMO

We herein present a unique and extremely rare fulminant case of Edwardsiella tarda infection-related necrotizing fasciitis. The patient had alcoholic cirrhosis and preferred to consume raw fish. He experienced painful swelling of the right forearm one day after he got a minor injury when falling from the ladder, and visited our hospital. His accompanied symptoms were diarrhea and general fatigue. His consciousness got deteriorated after the admission. The lesion of the right forearm had spread and the color had deteriorated with epidermolysis in a few hours. Necrotizing soft-tissue infection was suspected, and emergency debridement of the swollen forearm was performed 4 hours after the admission. However, unfortunately, he died of sepsis approximately 5 hours later. Histological examination of the biopsy specimen revealed features consistent with those of necrotizing fasciitis. The bacterial cultures of blood and the wound identified E. tarda. Since this microorganism is usually isolated from aquatic environments and can cause intestinal infection, sometimes followed by bacteremia especially in immunocompromised hosts, two possible infection routes were suspected. One route was from the skin injury, leading to bacteremia. Another possible route was per oral: orally taken E. tarda invaded deeper tissues from the intestine and reach the bloodstream, leading to extraintestinal infections, although direct evidence remains elusive. Raw fish eaten 1 week prior is considered to be the most possible contaminated food. Overall mortality rate of E. tarda bacteremia is very high and the clinician should pay attention on characteristic clinical findings of E. tarda infection on cirrhotic patients.


Assuntos
Bacteriemia , Fasciite Necrosante , Sepse , Masculino , Animais , Humanos , Fasciite Necrosante/diagnóstico , Cirrose Hepática Alcoólica/complicações , Edwardsiella tarda , Bacteriemia/microbiologia
5.
Dig Dis Sci ; 68(5): 1824-1834, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36478314

RESUMO

BACKGROUND: Nonsteroidal anti-inflammatory drug (NSAID)-induced enteropathy, the mechanism of which is involved in oxidative stress, can be lethal due to hemorrhage. Thus, we aimed to investigate the effect of hydrogen-rich water (HRW), in terms of oxidative stress, on intestinal mucosal damage as well as changes in the gut microbiome and the short-chain fatty acids (SCFAs) content in feces. METHODS: Hydrogen-rich water was orally administered for 5 days to investigate the effectiveness of indomethacin-induced enteropathy in mice. Small intestinal damage and luminal reactive oxygen species (ROS) were evaluated to investigate the ameliorating effects of hydrogen. Then, components of the gut microbiome were analyzed; fecal microbiota transplantation (FMT) was performed using the cecal contents obtained from mice drinking HRW. The cecal contents were analyzed for the SCFAs content. Finally, cells from the macrophage cell line RAW264 were co-cultured with the supernatants of cecal contents. RESULTS: Hydrogen-rich water significantly ameliorated IND-induced enteropathy histologically and reduced the expression of IND-induced inflammatory cytokines. Microscopic evaluation revealed that luminal ROS was significantly reduced and that HRW did not change the gut microbiota; however, FMT from HRW-treated animals ameliorated IND-induced enteropathy. The SCFA content in the cecal contents of HRW-treated animals was significantly higher than that in control animals. The supernatant had significantly increased interleukin-10 expression in RAW264 cells in vitro. CONCLUSION: Hydrogen-rich water ameliorated NSAID-induced enteropathy, not only via direct antioxidant effects but also via anti-inflammatory effects by increasing luminal SCFAs. These results suggest that hydrogen may have therapeutic potential in small intestinal inflammatory diseases.


Assuntos
Enteropatias , Camundongos , Animais , Espécies Reativas de Oxigênio , Enteropatias/induzido quimicamente , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios/efeitos adversos , Ácidos Graxos Voláteis , Hidrogênio/farmacologia , Hidrogênio/uso terapêutico , Água
6.
J Org Chem ; 87(14): 8928-8938, 2022 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-35785998

RESUMO

A series of σ-π extended octamethyltetrasilanes, which have phenothiazine, 9,9-dimethyl-9,10-dihydroacridine, or phenoxazine (1, 2, and 3) groups as donor moieties and thienopyrazine or benzothiadiazole (a and b) groups as acceptor fragments, has been prepared, and their optical properties have been studied as an extension of our work. All six compounds exhibited fluorescence in the solid state with maximum wavelengths centered in the range of 400 and 650 nm upon excitation by a UV lamp. Compound 2b showed apparent dual emission behavior in solution, which depends on solvent polarity, and a reversible photoluminescent change under mechanical and thermal stimuli in the solid state. Quantum chemical calculations suggest the contribution of a quasi-axial conformer of the 9,9-dimethyl-9,10-dihydroacridine moiety in 2b to the dual emission in solution and the mechanofluoroluminescence in the solid state, similarly to 1a. These studies provide new insight into the preparation of disilane-bridged triads capable of responding to multiple stimuli.


Assuntos
Luminescência , Fluorescência , Estrutura Molecular , Solventes
7.
J Gastroenterol Hepatol ; 37(9): 1768-1775, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35877196

RESUMO

BACKGROUND AND AIM: The functions of basophils have not been elucidated until recently because of their rarity. However, with recent developments in basophil-specific antibodies and basophil-deficient animals, the roles of basophils in various diseases related to chronic inflammation have been clarified. In this study, we aimed to investigate the roles of basophils in human ulcerative colitis (UC) and oxazolone (OXA) colitis using genetically engineered Mcpt8DTR mice. METHODS: Immunohistochemical staining of human colon specimens was performed to examine the involvement of basophils in the pathogenesis of UC. We examined the correlation between the number of infiltrating basophils and the UC endoscopic index of severity (UCEIS), Mayo score, and Matts score. We also examined the correlation between eosinophil count and basophil infiltration. In murine experiments, we examined whether basophil infiltration was involved in OXA-induced colitis and whether basophil depletion improved inflammation in Mcpt8DTR mice. RESULTS: Colonic basophil infiltration was significantly increased in patients with UC. There were significant correlations between UCEIS, Mayo score, Matts score, and the number of infiltrating basophils. In murine OXA-induced colitis, a significant increase in basophil infiltration was observed. When basophils were depleted by diphtheria toxin in Mcpt8DTR mice, inflammation improved significantly and mRNA expression of some proinflammatory cytokines, including Tnf-α and Ifn-γ decreased significantly. CONCLUSION: Basophil infiltration correlated with endoscopic, clinical, and pathological scores in human UC independently of eosinophil infiltration, and depletion of basophils ameliorated mucosal inflammation in murine OXA-induced colitis, collectively suggesting that basophils exert a proinflammatory role in chronic intestinal inflammation such as UC.


Assuntos
Colite Ulcerativa , Colite , Animais , Basófilos/metabolismo , Basófilos/patologia , Colite/induzido quimicamente , Colite/patologia , Colite Ulcerativa/patologia , Humanos , Inflamação/patologia , Intestinos/patologia , Camundongos , Oxazolona
8.
Dig Dis Sci ; 67(1): 121-133, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-33569665

RESUMO

BACKGROUND: Uric acid (UA) has anti- and pro-inflammatory properties. We previously revealed that elevated serum UA levels provide protection against murine small intestinal injury probably via luminal UA secreted in the small intestine. Luminal UA may act as an antioxidant, preventing microbiota vulnerability to oxidative stress. However, whether luminal UA is increased under hyperuricemia and plays a protective role in a dose-dependent manner as well as the mechanism by which luminal UA exerts its protective effects on enteropathy remains unknown. METHODS: Inosinic acid (IMP) (1000 mg/kg, i.p.) was administered to obtain high serum UA (HUA) and moderate serum UA (500 mg/kg IMP, i.p.) mice. UA concentrations and levels of oxidative stress markers in the serum and intestine were measured. Mice received indomethacin (20 mg/kg, i.p.) to evaluate the effects of UA on indomethacin-induced enteropathy. Reactive oxygen species (ROS) on the ileal mucosa were analyzed. The fecal microbiota of HUA mice was transplanted to investigate its effect on indomethacin-induced enteropathy. RESULTS: IMP increased luminal UA dose-dependently, with higher levels of luminal antioxidant markers. Indomethacin-induced enteropathy was significantly ameliorated in both UA-elevated groups, with decreased indomethacin-induced luminal ROS. The microbiota of HUA mice showed a significant increase in α-diversity and a significant difference in ß-diversity from the control. Fecal microbiota transplantation from HUA mice ameliorated indomethacin-induced enteropathy. CONCLUSIONS: The protective role of luminal UA in intestinal injury is likely exerted via oxidative stress elimination and microbiota composition modulation, preferably for gut immunity. Therefore, enhancing anaerobic conditions using antioxidants is a potential therapeutic target.


Assuntos
Transplante de Microbiota Fecal/métodos , Microbioma Gastrointestinal , Indometacina/farmacologia , Intestino Delgado , Ácido Úrico , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Antioxidantes/metabolismo , Modelos Animais de Doenças , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/imunologia , Enteropatias/induzido quimicamente , Enteropatias/metabolismo , Enteropatias/microbiologia , Enteropatias/terapia , Intestino Delgado/metabolismo , Intestino Delgado/microbiologia , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Fatores de Proteção , Espécies Reativas de Oxigênio/análise , Resultado do Tratamento , Ácido Úrico/sangue , Ácido Úrico/metabolismo
9.
Microcirculation ; 28(5): e12694, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33742518

RESUMO

INTRODUCTION: Innate lymphoid cells (ILCs) are abundant in the intestinal mucosa, forming boundaries externally. Herein, ILCs were directly obtained from intestinal lymph using a lymph fistula rat model and analyzed under physiological and pathological conditions. METHODS: Thoracic duct (TD) lymphocytes were collected by cannulation with/without preceded mesenteric lymphadenectomy, which were comparable to lymphocytes flowing through mesenteric lymphatic vessels (MLVs) or TD, respectively. The collected ILCs were classified according to gene transcription factors and analyzed by flow cytometry. The effect of IL-25 or indomethacin was studied. RESULTS: The proportion of total ILCs in the MLVs (MLV-ILCs) was significantly higher than that in TD (TD-ILCs, 0.01% vs. 0.003%, respectively). Physiologically, there were several significant differences in the MLV-ILCs compared with TD-ILCs, including the proportion of ILC2 (42.3% vs. 70.9%) and ILC3 (33.3% vs. 13.8%), and the proportion of α4-integrin-positive cells (36.8% vs. 0.3%). IL-25 significantly increased the proportion of MLV-ILC2 after 3 days. Indomethacin-induced intestinal injury increased the proportion of MLV-ILC3 in the early phase within 12 h. CONCLUSION: Intestinal ILCs were found to migrate through MLVs. The altered mobilization of MLV-ILCs after stimuli suggests that ILCs play an important role in regulating the immune responses at the secondary lymph nodes.


Assuntos
Imunidade Inata , Linfócitos , Animais , Indometacina , Inflamação , Mucosa Intestinal , Linfonodos , Ratos
10.
Chemistry ; 27(56): 13982-13990, 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34405922

RESUMO

Despite recent extensive studies on mechanochromic luminescence (MCL), rational control over the magnitude of the emission-wavelength shift in response to mechanical stimuli remains challenging. In the present study, a two-component donor-acceptor approach has been applied to create a variety of organic MCL composites that exhibit remarkable emission-wavelength switching. Dibenzofuran-based bis(1-pyrenylmethyl)diamine and typical organic fluorophores have been employed as donor and acceptor dyes, respectively. Outstanding wide-range MCL with an emission-wavelength shift of over 300 nm has been achieved by mixing the diamine with 3,4,9,10-perylenetetracarboxylic diimide. Unprecedented two-step MCL in response to mechanical stimuli of different intensity has also been realized for a two-component mixture with 9,10-anthraquinone. Fluorescence microscopy observations at the single-particle level revealed that the segregation and mixing of the two-component dyes contribute to the stimuli-responsive emission-color switching of the MCL composites.

11.
Hepatol Res ; 51(5): 580-592, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33247991

RESUMO

AIM: We recently reported that lipoprotein lipase (LPL)-mediated free cholesterol (FC) accumulation in hepatic stellate cells (HSCs) augmented liver fibrosis in non-alcoholic steatohepatitis (NASH). The aim of the present study was to explore the role of angiopoietin-like protein 4 (Angptl4), an LPL inhibitor, in the pathogenesis of liver fibrosis in NASH. METHODS: Angptl4-deficient or wild-type mice were used to investigate the role of Angptl4 in the pathogenesis of NASH induced by feeding a methionine- and choline-deficient diet. We also examined the effect of Angptl4 on FC accumulation in HSCs, and the subsequent activation of HSCs, using Angptl4-deficient HSCs. RESULTS: In the NASH model, Angptl4-deficient mice had significantly aggravated liver fibrosis and activated HSCs without enhancement of hepatocellular injury, liver inflammation, or liver angiogenesis. FC levels were significantly higher in HSCs from Angptl4-deficient mice than in those from wild-type mice. Treatment with Angptl4 reversed low-density lipoprotein-induced FC accumulation in HSCs through the inhibition of LPL. The Angptl4 deficiency-induced FC accumulation in HSCs suppressed HSC expression of the transforming growth factor-ß (TGF-ß) pseudoreceptor, bone morphogenetic protein, and activin membrane-bound inhibitor, and sensitized HSCs to TGF-ß-induced activation in vivo and in vitro. CONCLUSIONS: Angptl4 plays an important role in the pathogenesis of FC accumulation in HSCs. In addition, regulation of FC levels in HSCs by Angptl4 plays a critical role in the pathogenesis of liver fibrosis in NASH. Thus, Angptl4 could represent a novel therapeutic option for NASH.

12.
J Gastroenterol Hepatol ; 36(11): 3140-3148, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34368996

RESUMO

BACKGROUND AND AIM: The artificial sweetener acesulfame potassium (ACK) is officially approved as safe for intake and has been used in processed foods. However, ACKs have been reported to induce metabolic syndrome, along with alteration of the gut microbiota in mice. In recent years, studies have suggested that this artificial sweetener promotes myeloperoxidase reactivity in Crohn's disease-like ileitis. We aimed to investigate the effect of ACK on the intestinal mucosa and gut microbiota of normal mice. METHODS: Acesulfame potassium was administered to C57BL/6J mice (8 weeks old) via free drinking. Intestinal damage was evaluated histologically, and messenger RNA (mRNA) levels of TNF-α, IFN-γ, IL1-ß, MAdCAM-1, GLP1R, and GLP2R were determined with quantitative reverse transcription polymerase chain reaction (qRT-PCR). Immunohistochemistry was performed to examine the expression of MAdCAM-1 in the small intestine. The composition of gut microbiota was assessed using high-throughput sequencing. We performed intravital microscopic observation to examine if ACK altered lymphocyte migration to the intestinal microvessels. RESULTS: Acesulfame potassium increased the expression of proinflammatory cytokines, decreased the expression of GLP-1R and GLP-2R, and induced small intestinal injury with an increase in intestinal permeability, and ACK treatment induced microbial changes, but the transfer of feces alone from ACK mice did not reproduce intestinal damage in recipient mice. ACK treatment significantly increased the migration of lymphocytes to intestinal microvessels. CONCLUSION: Acesulfame potassium induces dysbiosis and intestinal injury with enhanced lymphocyte migration to intestinal mucosa. Massive use of non-caloric artificial sweeteners may not be as safe as we think.


Assuntos
Disbiose , Intestinos , Tiazinas , Animais , Movimento Celular , Disbiose/induzido quimicamente , Mucosa Intestinal , Intestinos/lesões , Linfócitos , Camundongos , Camundongos Endogâmicos C57BL , Edulcorantes/toxicidade , Tiazinas/toxicidade
13.
J Gastroenterol Hepatol ; 36(9): 2523-2530, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33783040

RESUMO

BACKGROUND AND AIM: The small intestine plays a central role in gut immunity, and enhanced lymphocyte migration is involved in the pathophysiology of various enteropathy. Bile acid (BA) is closely related to lipid metabolism and gut microbiota and essential for gut homeostasis. However, the effects of BA on gut immunity have not been studied in detail, especially on the small intestine and lymphocyte migration. Therefore, we aimed to investigate the effect of BA on small intestinal lymphocyte microcirculation. METHODS: The effect of deoxycholic acid (DCA), taurocholic acid (tCA), or cholic acid (CA) on the indomethacin (IND)-induced small intestinal enteropathy in mice was investigated. Lymphocyte movements were evaluated after exposure to BA using intravital microscopy. The effects of BA on surface expression of adhesion molecules on the vascular endothelium and lymphocytes through BA receptors were examined in vitro. RESULTS: IND-induced small intestinal enteropathy was histologically aggravated by DCA treatment alone. The expression of adhesion molecules ICAM-1 and VCAM-1 was significantly enhanced by DCA. Exposure to DCA increased lymphocyte adhesion in the microvessels of the ileum, which was partially blocked by anti-α4ß1 integrin antibody in vivo. The expression of ICAM-1 and VCAM-1 was significantly enhanced by DCA in vitro, which was partially suppressed by the sphingosine-1-phosphate receptor 2 (S1PR2) antagonist. The S1PR2 antagonist significantly ameliorated IND-induced and DCA-exaggerated small intestinal injury. CONCLUSION: DCA exacerbated IND-induced small intestinal enteropathy. DCA directly acts on the vascular endothelium and enhances the expression levels of adhesion molecules partially via S1PR2, leading to enhanced small intestinal lymphocyte migration.


Assuntos
Movimento Celular , Ácido Desoxicólico , Endotélio Vascular , Ileíte , Intestino Delgado , Linfócitos , Animais , Ácidos e Sais Biliares/efeitos adversos , Ácidos e Sais Biliares/farmacologia , Movimento Celular/efeitos dos fármacos , Movimento Celular/imunologia , Ácidos Cólicos/efeitos adversos , Ácidos Cólicos/farmacologia , Ácido Desoxicólico/efeitos adversos , Ácido Desoxicólico/farmacologia , Modelos Animais de Doenças , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/imunologia , Endotélio Vascular/fisiopatologia , Ileíte/induzido quimicamente , Ileíte/imunologia , Ileíte/fisiopatologia , Íleo/irrigação sanguínea , Íleo/efeitos dos fármacos , Íleo/imunologia , Íleo/fisiopatologia , Molécula 1 de Adesão Intercelular/biossíntese , Molécula 1 de Adesão Intercelular/imunologia , Intestino Delgado/irrigação sanguínea , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/imunologia , Intestino Delgado/fisiopatologia , Microscopia Intravital , Linfócitos/efeitos dos fármacos , Linfócitos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microvasos/efeitos dos fármacos , Microvasos/imunologia , Ratos , Ratos Wistar , Receptores de Esfingosina-1-Fosfato/antagonistas & inibidores , Circulação Esplâncnica/imunologia , Molécula 1 de Adesão de Célula Vascular/biossíntese , Molécula 1 de Adesão de Célula Vascular/imunologia
14.
Angew Chem Int Ed Engl ; 60(42): 22871-22878, 2021 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-34427025

RESUMO

A σ-π extended aryldisilane, comprising a thienopyrazine group as an acceptor fragment and phenothiazine groups as the donor moiety, has been prepared through the introduction of two Si-Si bridges (compound 1). X-ray diffraction analysis determined the crystal structure of 1, and experimental and theoretical approaches investigated its optical properties. Solvatochromic studies revealed the dual emission of 1 in all solvents tested. Compound 1 also exhibited fluorescence in the solid state upon excitation with a hand-held UV lamp, as well as mechanochromic luminescent properties. The packing mode in the crystal structure, variation of phenothiazine conformation, morphological changes between crystalline and amorphous phases are the major factors showing reversible fluorescence under external stimuli. A theoretical conformer study found that 1 exists in distinct conformational groups differing in Gibbs free energy by less than 3 kcal mol-1 . The conformer in the crystalline state of 1 can promote the complete separation of the HOMO and LUMO between the phenothiazine donor and the thienopyrazine acceptor, linked by the disilane linker. HOMO-LUMO energy transition in the crystalline state is forbidden due to the lack of frontier orbital overlap. Crystalline state emission showed LUMO → HOMO-1 transition (locally excited (LE) state). In the amorphous state, the partial presence of quasi-axial conformers allows intramolecular charge-transfer type emission via energy transfer from dominant quasi-equatorial conformers. The strategy proposed in this work provides important guidance for developing stimuli-responsive materials with controlled excited states.

15.
Nihon Shokakibyo Gakkai Zasshi ; 117(11): 978-984, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-33177260

RESUMO

A 69-year-old man had been intermittently experiencing abdominal pain from his 30s and was diagnosed with colonic diverticulitis. He further experienced right lower abdominal pain and received treatment. However, his condition did not improve, and he was referred to the National Defense Medical College Hospital. His abdominal pain episodes continued even after treatment for few weeks;subsequently, familial Mediterranean fever (FMF) was suspected based on the clinical course because of elevated inflammatory responses, although his body temperature was ≤38°C. After administrating colchicine as a diagnostic treatment, the repeated abdominal pain disappeared. Considering the other findings and genetic examination that showed the representative gene mutation of MEFV (M694I), he was diagnosed with FMF. This case indicates that high body temperature, one of the primary diagnostic criteria of FMF, is sometimes not evident in elderly patients, thereby causing potential misdiagnosis in some elderly patients with FMF.


Assuntos
Doença Diverticular do Colo , Febre Familiar do Mediterrâneo , Dor Abdominal/etiologia , Idoso , Febre Familiar do Mediterrâneo/diagnóstico , Febre Familiar do Mediterrâneo/tratamento farmacológico , Febre Familiar do Mediterrâneo/genética , Febre , Humanos , Masculino , Mutação , Pirina/genética
16.
Org Biomol Chem ; 16(2): 213-222, 2018 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-29136083

RESUMO

Chiral anionic species are ubiquitous and play important roles in biological systems. Despite the recent advancements in synthetic anion receptors bearing urea functionalities, urea-based chiral solvating agents (CSAs) that can separate the NMR signals of racemic anions remain limited. Herein, three dibenzofuran-based C2-symmetric chiral bisureas were synthesized from the reaction of (R,R)-4,6-bis(1-aminopropyl)dibenzo[b,d]furan with phenyl isocyanate, phenyl thioisocyanate, or tosyl isocyanate. The chiral anion recognition properties of these bisureas were examined by 1H NMR spectroscopy using dl-tetrabutylammonium mandelate (TBAM) as a model substrate. A clear baseline separation of the enantiomeric signals of the benzylic proton of TBAM was achieved upon mixing with 0.5 equivalents of bis(phenylurea). In contrast to previous urea-based chiral anion receptors that differentiate the enantiomers of chiral anions by forming 1 : 1 host-guest complexes, a high chiral recognition ability of chiral bis(phenylurea) was achieved owing to the generation of an equilibrium between free guests, 1 : 1 host-guest complexes, and 1 : 2 host-guest complexes. Chiral bis(phenylurea) was also successfully employed in the separation of the enantiomeric 1H NMR signals of various racemic anions.


Assuntos
Ânions/química , Espectroscopia de Ressonância Magnética/métodos , Ânions/análise , Compostos de Fenilureia/química , Compostos de Amônio Quaternário/química , Solubilidade , Estereoisomerismo , Ureia/química
17.
Biosci Biotechnol Biochem ; 80(4): 779-85, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26967638

RESUMO

Osteoporosis is a debilitating disease caused by decreased bone density. Compounds with anti-osteoclastic activity, such as bisphosphonates, may help in the prevention and treatment of osteoporosis. Herein, we determined the inhibitory effects of ginger hexane extract (GHE) on receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclastogenesis in RAW264.7 cells. The results showed that GHE (1) suppressed osteoclast differentiation and the formation of actin rings; (2) inhibited the expression of Nfatc1, a master transcriptional factor for osteoclast differentiation, in a dose-dependent manner (10-20 µg/mL); and (3) inhibited other osteoclastogenesis-related genes, such as Oscar, Dc-stamp, Trap, and Mmp9. These findings suggest that GHE may be used to prevent and treat osteoporosis by inhibiting osteoclast differentiation.


Assuntos
Diferenciação Celular/fisiologia , Hexanos/química , Osteoclastos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Ligante RANK/fisiologia , Zingiber officinale/química , Animais , Linhagem Celular , Camundongos , Osteoclastos/citologia , Extratos Vegetais/química
18.
Chem Asian J ; : e202400293, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38750665

RESUMO

Stimuli-responsive organic luminescent crystals have attracted significant attention in recent years for their potential in sensor and memory applications. While turn-on luminescence is superior in detection sensitivity compared with turn-off luminescence, the development of organic crystals that exhibit turn-on luminescence in response to multiple stimuli remains a significant challenge. Herein, the crystals of chiral bisimidazolyl 1,1'-bi-2-naphthol (BINOL) dimethyl ether have exhibited a dual-stimuli-responsive turn-on luminescence based on two distinct mechanisms. In the crystalline state, luminescence was substantially quenched by the intermolecular hydrogen bonds between the imidazole rings. Mechanical stimulation induced a transition to a blue-violet-emissive amorphous state. In contrast, thermal stimulation produced an orange luminescence, attributed to excited-state intramolecular proton transfer (ESIPT) luminescence from thermally demethylated products. Furthermore, the thermally induced state exhibited circularly polarized luminescence (CPL), marking a rare instance of stimuli-responsive turn-on CPL in a solid-state system. This study provides new insights into environmental and structural factors for solid-state luminescent properties and advances the design guidelines for multifunctional luminescent sensors.

19.
Intern Med ; 63(3): 379-383, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37316275

RESUMO

Little is known about iatrogenic splenic injury (SI) as an adverse event after colonoscopy. SI is sometimes fatal because of hemorrhaging. We herein report a man who developed SI after colonoscopy. He recovered conservatively. His history of left hydronephrosis and insertion with a maximally stiffened scope were suspected as possible risk factors. Endoscopists should consider the possibility of SI when they encounter patients suffering from left-sided abdominal pain after colonoscopy. Careful interview concerning the medical history and gentle maneuvering around the splenic flexure can help avoid SI.


Assuntos
Ruptura Esplênica , Masculino , Humanos , Ruptura Esplênica/diagnóstico por imagem , Ruptura Esplênica/etiologia , Esplenectomia/efeitos adversos , Hemorragia/etiologia , Colonoscopia/efeitos adversos
20.
Pancreas ; 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38696351

RESUMO

BACKGROUND: Although the involvement of intestinal microbiota in innate immunity has been reported recently, the pathogenicity of autoimmune pancreatitis (AIP) remains unclear. This study aimed to investigate whether probiotics ameliorate inflammation in AIP through interactions with innate immunity. METHODS: The AIP mouse model was generated by intraperitoneal administration of E. coli to C56BL/6 female mice. Alterations in the intestinal microbiota in the AIP group were evaluated using high-throughput sequencing. Peritoneal macrophages (PMs) were collected and cocultured in vitro with Lactobacillus gasseri (LG) or ligands of toll-like receptors (TLRs). LG was administered intraperitoneally to AIP model mice, and pancreatitis activity was evaluated to examine the ameliorative effects of LG. RESULTS: In the AIP model mice, inflammation was significantly induced in the pancreas, and the intestinal microbiota was altered with decreased LG. Antimicrobial treatment suppressed pancreatitis. In vitro, E. coli stimulation increased inflammatory cytokine expression, which was significantly decreased when the LG or TLR7 ligand was cocultured with PMs. Intraperitoneal administration of LG to AIP model mice significantly suppressed pancreatitis. CONCLUSION: The mouse model demonstrated the involvement of intestinal microbiota in pancreatitis, and LG administration suppressed pancreatitis, possibly through TLR7 signaling in PMs. LG may be a helpful probiotic for treating AIP.

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