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1.
Nanotechnology ; 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38749413

RESUMO

Self-assembly processes are widely used in nature to form hierarchically organized structures, prompting us to investigate such processes at the macroscopic scale. We report an unprecedented approach toward the self-assembly of alkyl-fullerene (C60) derivatives into a hexagonal array of hemispherical microparticles akin to the morphology of a compound eye. The method includes casting solvated alkyl-C60compound on an air/water interface followed by controlled evaporation of the solvent under atmosphere-sealed conditions. This leads to the formation of a thin film floating on water with a diameter of up to 1.3 centimeters and exhibiting a hexagonally-packed hemispherical structure with a diameter of approximately 38 µm. Various measurements of the formed film reveal that amorphousness is necessary for suppressing uncontrollable crystallization, which affects the microparticle size and film formation mechanism. We tested the feasibility of this approach for the self-assembly of a relatively common C60derivative, [6,6]-phenyl-C61-butyric acid methyl ester (PC61BM), resulting in the formation of a film with a similar pattern of hexagonally-packed larger microparticles approximately 152 µm in size of diameter. .

2.
Angew Chem Int Ed Engl ; 63(20): e202402874, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38512717

RESUMO

The development of optoelectronically-active soft materials is drawing attention to the application of soft electronics. A room-temperature solvent-free liquid obtained by modifying a π-conjugated moiety with flexible yet bulky alkyl chains is a promising functional soft material. Tuning the elastic modulus (G') is essential for employing optoelectronically-active alkyl-π liquids in deformable devices. However, the range of G' achieved through the molecular design of alkyl-π liquids is limited. We report herein a method for controlling G' of alkyl-π liquids by gelation. Adding 1 wt % low-molecular-weight gelator formed the alkyl-π functional molecular gel (FMG) and increased G' of alkyl-π liquids by up to seven orders of magnitude while retaining the optical properties. Because alkyl-π FMGs have functional π-moieties in the gel medium, this new class of gels has a much higher content of π-moieties of up to 59 wt % compared to conventional π-gels of only a few wt %. More importantly, the gel state has a 23 % higher charge-retention capacity than the liquid, providing better performance in deformable mechanoelectric generator-electret devices. The strategy used in this study is a novel approach for developing next-generation optoelectronically-active FMG materials.

3.
Am J Pathol ; 194(5): 828-848, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38320632

RESUMO

Cancer-associated fibroblasts (CAFs) in the tumor microenvironment are involved in the progression of various cancers, including esophageal squamous cell carcinoma (ESCC). CAF-like cells were generated through direct co-culture of human bone marrow-derived mesenchymal stem cells, one of CAF origins, with ESCC cells. Periostin (POSTN) was found to be highly expressed in CAF-like cells. After direct co-culture, ESCC cells showed increased malignant phenotypes, such as survival, growth, and migration, as well as increased phosphorylation of Akt and extracellular signal-regulated kinase (Erk). Recombinant human POSTN activated Akt and Erk signaling pathways in ESCC cells, enhancing survival and migration. The suppression of POSTN in CAF-like cells by siRNA during direct co-culture also suppressed enhanced survival and migration in ESCC cells. In ESCC cells, knockdown of POSTN receptor integrin ß4 inhibited Akt and Erk phosphorylation, and survival and migration increased by POSTN. POSTN also enhanced mesenchymal stem cell and macrophage migration and endowed macrophages with tumor-associated macrophage-like properties. Immunohistochemistry showed that high POSTN expression in the cancer stroma was significantly associated with tumor invasion depth, lymphatic and blood vessel invasion, higher pathologic stage, CAF marker expression, and infiltrating tumor-associated macrophage numbers. Moreover, patients with ESCC with high POSTN expression exhibited poor postoperative outcomes. Thus, CAF-secreted POSTN contributed to tumor microenvironment development. These results indicate that POSTN may be a novel therapeutic target for ESCC.


Assuntos
Fibroblastos Associados a Câncer , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Fibroblastos Associados a Câncer/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Periostina , Proteínas Proto-Oncogênicas c-akt/metabolismo , Microambiente Tumoral
6.
Int J Clin Oncol ; 29(2): 142-148, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38063978

RESUMO

BACKGROUND: Neoadjuvant docetaxel, cisplatin, and 5-fluorouracil (DCF) therapy is a new standard for locally advanced esophageal squamous cell carcinoma. The optimal timing of pegfilgrastim with the DCF regimen to prevent febrile neutropenia (FN) remains controversial. The effectiveness of concomitant pegfilgrastim administration with continuous 5-fluorouracil (5-FU) infusion in the DCF regimen was therefore assessed. METHODS: All patients who received neoadjuvant DCF for esophageal cancer were retrospectively assessed. Patients who had been scheduled to receive pegfilgrastim on days 3-5 (early group) or days 7-9 (regular group) of the DCF regimen were included. Uni- and multivariate analyses were used to assess risk factors for FN. RESULTS: Eighty-eight patients were included in the analysis. The 26 patients in the early group received pegfilgrastim as scheduled. In the 62 patients of the regular group, 51 received pegfilgrastim at a median of 7 days after starting DCF chemotherapy. However, 11 patients in the regular group could not receive pegfilgrastim. Twenty-two patients of the regular group and 2 patients of the early group developed FN after the first session of DCF. Early administration of pegfilgrastim and grade 4 neutropenia were significantly associated with onset of FN, with multivariate analysis identifying early administration of pegfilgrastim as an independent preventive factor and grade 4 neutropenia as a risk factor, after adjusting for sex and age. CONCLUSION: Early pegfilgrastim administration is a safe approach that reduces the incidence of FN in DCF therapy. Using pegfilgrastim with continuous 5-FU infusion in the DCF regimen represents a reasonable option to prevent FN.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Filgrastim , Neutropenia , Polietilenoglicóis , Humanos , Cisplatino , Docetaxel , Neoplasias Esofágicas/patologia , Fluoruracila , Terapia Neoadjuvante , Estudos Retrospectivos , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/etiologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neutropenia/induzido quimicamente , Neutropenia/tratamento farmacológico , Neutropenia/prevenção & controle
7.
Anticancer Res ; 44(1): 229-237, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38159989

RESUMO

BACKGROUND/AIM: The albumin and derived neutrophil-to-lymphocyte ratio (Alb-dNLR) score, which combines an inflammation index with a nutritional index, has recently been reported as a useful prognostic marker in various cancers. However, evaluation of the usefulness of Alb-dNLR score in patients with locally advanced rectal cancer (LARC) undergoing neoadjuvant chemoradiotherapy (NACRT) has not been reported yet. PATIENTS AND METHODS: This retrospective study included 69 patients with LARC undergoing NACRT followed by surgery between November 2005 and July 2020. The cutoff value of the Alb-dNLR score for relapse-free survival (RFS) was determined using a receiver operating characteristic curve. Patients were divided into high and low Alb-dNLR-score groups and analyzed for RFS and overall survival (OS). RESULTS: A total of 10 patients had high Alb-dNLR scores, and 59 had low Alb-dNLR scores. The high Alb-dNLR-score group had significantly higher rates of open surgery (70.0% vs. 28.8%; p<0.026), greater intraoperative blood loss (2,009 g vs. 421 g; p<0.001), and longer postoperative hospital stays (70 days vs. 42 days, p=0.012) than those of the low-Alb-dNLR-score group. The high Alb-dNLR-score group further demonstrated significantly worse RFS and OS than the low Alb-dNLR-score group (both p<0.001). Multivariate analysis identified the Alb-dNLR score as the most independent prognostic factor for RFS (hazard ratio=5.27; 95% confidence interval=2.09-13.27; p<0.001). CONCLUSION: The Alb-dNLR score is a valuable prognostic marker for predicting the oncological outcomes in patients with LARC undergoing NACRT.


Assuntos
Neutrófilos , Neoplasias Retais , Humanos , Prognóstico , Terapia Neoadjuvante , Estudos Retrospectivos , Recidiva Local de Neoplasia , Linfócitos , Albuminas/uso terapêutico , Quimiorradioterapia
8.
J Am Chem Soc ; 145(46): 25160-25169, 2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-37943955

RESUMO

Although strong chiral self-sorting often emerges in extended covalent or supramolecular polymers, the phenomenon is generally weak in discrete assemblies (e.g., dimers and oligomers) of small molecules due to the lack of a cooperative growth mechanism. Consequently, chiral self-sorting has been overlooked in the design of switchable and metastable discrete supramolecular structures. Here, we report a butyl-benzo[h]quinoline-based iridium(III) complex (Bu-Ir) with helical chirality at its metal center, which forms preferentially a homochiral dimer and exhibits thermo-/mechano-chromism based on a monomer-dimer transformation. While a five-coordinate monomer is formed in a racemic or an enantiopure Bu-Ir solution at 25 °C, a six-coordinate homochiral dimer complex is formed almost exclusively at low temperatures, with a higher degree of dimerization in enantiopure Bu-Ir solution. Estimation of apparent dimerization binding constants (K) and thermodynamic parameters (ΔH and ΔS) based on variable temperature ultraviolet-visible (UV-vis) and 1H NMR spectra reveals a strong preference for homochiral dimerization (largest known value for the coordination complex, Khomo/Khetero > 50). Notably, crystals of the homochiral dimer are metastable, undergoing a distinct color change upon grinding (from yellow to red) due to mechanical cleavage of coordination bonds (i.e., a dimer to monomer transformation). A comparison with control compounds having different substituents (proton, methyl, isopropyl, and phenyl groups) reveals that Bu-Ir dimerization involves both strong homochiral self-sorting preference and connected thermo-/mechano-chromic behavior, which is based on matched propeller-shaped chirality and subtle steric repulsion between alkyl substituents that render the homochiral dimer switchable and metastable. These findings provide substantial insights into the emergence of dynamic functionality based on the rational design of discrete chiral assemblies.

9.
Cells ; 12(22)2023 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-37998338

RESUMO

Tumor-associated macrophages (TAMs), one of the major components of the tumor microenvironment, contribute to the progression of esophageal squamous cell carcinoma (ESCC). We previously established a direct co-culture system of human ESCC cells and macrophages and reported the promotion of malignant phenotypes, such as survival, growth, and migration, in ESCC cells. These findings suggested that direct interactions between cancer cells and macrophages contribute to the malignancy of ESCC, but its underlying mechanisms remain unclear. In this study, we compared the expression levels of the interferon-induced genes between mono- and co-cultured ESCC cells using a cDNA microarray and found that interferon-inducible protein 16 (IFI16) was most significantly upregulated in co-cultured ESCC cells. IFI16 knockdown suppressed malignant phenotypes and also decreased the secretion of interleukin-1α (IL-1α) from ESCC cells. Additionally, recombinant IL-1α enhanced malignant phenotypes of ESCC cells through the Erk and NF-κB signaling. Immunohistochemistry revealed that high IFI16 expression in human ESCC tissues tended to be associated with disease-free survival and was significantly associated with tumor depth, lymph node metastasis, and macrophage infiltration. The results of this study reveal that IFI16 is involved in ESCC progression via IL-1α and imply the potential of IFI16 as a novel prognostic factor for ESCC.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/patologia , Interferons/metabolismo , Interleucina-1alfa/metabolismo , Macrófagos/metabolismo , Processos Neoplásicos , Proteínas Nucleares/metabolismo , Fosfoproteínas/metabolismo , Microambiente Tumoral
10.
Mater Horiz ; 10(9): 3458-3466, 2023 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-37350547

RESUMO

Special attention is being paid to the potential applicability of various soft electronics in deformable/wearable devices. These devices must be constantly connected to energy sources to ensure their uninterrupted operation. Electrets, which are capable of retaining quasi-permanent electric charges inside or on the surface of materials, are expected to be a battery-less power source. Here, we present a strategy for harvesting the charges in alkyl-C60 liquids. Suitable substitution of bulky yet flexible branched long-alkyl chains generated C60-mono-adducts and regioisomeric bis-adducts as room-temperature solvent-free liquids. These alkyl-C60 liquids were negatively poled by the corona-discharging and soaked in nylon fabric. The liquid of the C60 bis-adduct exhibited better charge retention in comparison to the liquid of the C60 mono-adduct. This suggests that the bulky long-alkyl chains provided proper insulation for the C60 core and charge trapping in the liquid. This charge-trapping behaviour and the inherent fluidity of the alkyl-C60 liquids enabled their fabrication into deformable mechanoelectric generator (MEG) devices. The MEG exhibited applicability as a deformable micropower source or vibration sensor by generating output voltage pulses even under folded/twisted/rolled conditions. The alkylated-liquid-based MEGs worked at frequencies similar to human body motion, showing promising potential for body motion sensors and healthcare applications.

11.
J Clin Med ; 12(10)2023 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-37240476

RESUMO

Diarrhea-predominant irritable bowel syndrome (IBS-D)-like symptoms are distressing for patients with quiescent Crohn's disease (qCD) and worsen their quality of life. In the present study, we assessed the effect of the probiotic Bifidobacterium bifidum G9-1 (BBG9-1) on the intestinal environment and clinical features in patients with qCD. Eleven patients with qCD, who met the Rome III diagnostic criteria for IBS-D, received BBG9-1 (24 mg) orally three times daily for 4 weeks. Indices of the intestinal environment (fecal calprotectin level and gut microbiome) and clinical features (CD/IBS-related symptoms, quality of life and stool irregularities) were evaluated before and after treatment. Treatment with BBG9-1 tended to reduce the IBS severity index in the studied patients (p = 0.07). Among gastrointestinal symptoms, abdominal pain and dyspepsia tended to be improved by the BBG9-1 treatment (p = 0.07 and p = 0.07, respectively), and IBD-related QOL showed a significant improvement (p = 0.007). With regard to mental status, the patient anxiety score was significantly lower at the endpoint of BBG9-1 treatment than at the baseline (p = 0.03). Although BBG9-1 treatment did not affect the fecal calprotectin level, it suppressed the serum MCP-1 level significantly and increased the abundance of intestinal Bacteroides in the study patients. The probiotic BBG9-1 is able to improve IBD-related QOL with a reduction of anxiety score in patients with quiescent CD and IBS-D-like symptoms.

12.
J Phys Chem B ; 127(21): 4870-4885, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37093669

RESUMO

Functional molecular liquids (FMLs) based on alkylated π-conjugated molecules have attracted attention as solvent-free and nonvolatile liquid materials with prominent optoelectronic features. Recently, novel FML compounds containing pyrene as the functional core were synthesized, and their rheological and photochemical properties were investigated. Although the molecules differ only in the number of alkyl chain substituents and their substitution positions, their viscosity coefficients are largely different beyond the Stokes-Einstein relation on the assumption of identical microscopic friction, indicating that local microscopic molecular interactions are crucial for the macroscopic rheological properties. Here, we report a theoretical study on the rheological properties of the alkyl-pyrene liquids by means of atomistic molecular dynamics (MD) simulations. We performed long-time MD simulations for tens of microseconds to obtain ample statistical samples of the alkyl-pyrene liquids and analyzed their liquid structures and diffusion dynamics based on spatiotemporal correlation functions. We found the formation of characteristic local liquid structures of π-π stacking of the pyrene moieties and locally anisotropic and anomalous diffusion dynamics, which remarkably vary depending on the alkyl substituent patterns. The present results provide an atomistic insight into the macroscopic rheological properties of alkyl-π FMLs and molecular design strategy for them.

13.
ACS Sens ; 8(4): 1585-1592, 2023 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-37029744

RESUMO

Formaldehyde (FA) is a deleterious C1 pollutant commonly found in the interiors of modern buildings. C1 chemicals are generally more toxic than the corresponding C2 chemicals, but the selective discrimination of C1 and C2 chemicals using simple sensory systems is usually challenging. Here, we report the selective detection of FA vapor using a chemiresistive sensor array composed of modified hydroxylamine salts (MHAs, ArCH2ONH2·HCl) and single-walled carbon nanotubes (SWCNT). By screening 32 types of MHAs, we have identified an ideal sensor array that exhibits a characteristic response pattern for FA. Thus, trace FA (0.02-0.05 ppm in air) can be clearly discriminated from the corresponding C2 chemical, acetaldehyde (AA). This system has been extended to discriminate methanol (C1) from ethanol (C2) in combination with the catalytic conversion of these alcohols to their corresponding aldehydes. Our system offers portable and reliable chemical sensors that discriminate the subtle differences between C1 and C2 chemicals, enabling advanced environmental monitoring and healthcare applications.


Assuntos
Nanotubos de Carbono , Hidroxilamina , Aldeídos , Formaldeído , Hidroxilaminas
14.
Chemistry ; 29(21): e202203775, 2023 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-36715059

RESUMO

Alkyl-π functional molecular liquids (FMLs) are of interest for fabricating soft electronic devices due to their fluidic nature and innate optoelectronic functions from the π-conjugated moiety. However, predictable development of alkyl-π FMLs with the desired liquid and optoelectronic properties is challenging. A series of alkyl-distyrylbenzene (DSB) liquids was studied in terms of the substituent position effect by attaching 2-octyldodecyl chains at (2,4-), (2,5-), (2,6-), and (3,5-). The effect of the alkyl chain length was investigated by attaching 2-hexyldecyl, 2-decyltetradecyl (C10 C14 ), and 2-dodecylhexadecyl at the (2,5-) substituent position. The 2,5-C10 C14 substituent pattern constructed a superior alkyl-DSB liquid with a lower viscosity, intrinsic optical properties, and high thermal- and photo-stabilities. The discovered 2,5-C10 C14 was applied to dicyanostyrylbenzene and comparable liquid physical and optical superiorities were confirmed. This molecular design is useful for creating alkyl-π FMLs with the aforementioned advantages, which are applicable for deformable and flowable optoelectronic devices.

15.
Gan To Kagaku Ryoho ; 50(13): 1374-1377, 2023 Dec.
Artigo em Japonês | MEDLINE | ID: mdl-38303279

RESUMO

Adenocarcinoma of the rectum and anal canal with inguinal lymph node metastasis(ILNM)is rare and the prognosis is generally poor. The aim of this study was to clarify the clinical significance of selective inguinal lymph node dissection and total mesorectal excision after preoperative therapy for adenocarcinoma of the rectum and anorectal canal with clinically suspected ILNM. Of the 15 patients, 11 received preoperative chemoradiotherapy, 3 received chemotherapy, and 1 received chemotherapy after chemoradiotherapy. 14 patients received preoperative therapy followed by FDG-PET scans were performed in 14 patients after preoperative treatment. 5 patients had negative FDG accumulation in inguinal lymph nodes on FDG-PET scans, and postoperative pathological diagnosis was also negative for metastasis in the inguinal lymph nodes. Of the 9 patients with positive FDG accumulation, 4 had pathologically positive inguinal lymph nodes, 7 had postoperative inguinal seroma, the 5-year survival rate was 77.5%, and the 5-year recurrence-free survival rate was 64.2%. No patient had a recurrence in the inguinal region. Patients with adenocarcinoma of the rectum and anal canal with clinical ILNM had good long-term survival after radical resection with preoperative therapy.


Assuntos
Adenocarcinoma , Neoplasias do Ânus , Neoplasias Retais , Humanos , Reto/patologia , Metástase Linfática/patologia , Canal Anal/patologia , Fluordesoxiglucose F18 , Canal Inguinal/patologia , Excisão de Linfonodo , Linfonodos/cirurgia , Linfonodos/patologia , Neoplasias Retais/cirurgia , Neoplasias Retais/patologia , Adenocarcinoma/cirurgia
16.
Maxillofac Plast Reconstr Surg ; 44(1): 6, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-35229188

RESUMO

BACKGROUND: No studies have compared the outcomes of direct perineurial suture with vein graft cuff repair and indirect collagen allograft repair of the lingual nerve following an injury. Therefore, we evaluated and compared the outcomes of each over a 1-year observation period. We retrospectively assessed 20 patients who had undergone microneurosurgical repair of unilateral lingual nerve injuries at the Wakayama Medical University Hospital between May 2015 and March 2019. We utilized two different methods for lingual nerve repair, i.e., direct perineurial repair with a vein graft cuff and interpositional collagen allograft repair. Sensory and taste function in the lingual nerve were preoperatively evaluated using a static two-point discrimination test, superficial pain/tactile sensation test, tests for the pressure pain threshold (Semmens-Weinstein monofilament), test for thermal discrimination hot and cold sensation, and a taste discrimination test. These tests were performed again at 6 and 12 months postoperatively. RESULTS: Compared to the preoperative conditions, all patients showed improved sensory reactions. Functional sensory recovery outcomes were defined by Pogrel's criteria, Medical Research Council Scale grades, and functional sensory recovery. In each group, all patients improved after the operation. However, the operation time was significantly shorter for an interpositional collagen allograft repair as compared to that for a direct perineurial repair with a vein graft cuff. CONCLUSIONS: There were no statistically significant differences between the two repair Methods, except for the operation time. Both methods led to satisfactory results for all criteria. From an economic point of view, direct perineurial repair with a vein graft cuff is meaningful; however, the esthetic effect on the donor site should be considered. Conversely, interpositional collagen allograft repair has the advantage of a greatly shortened operation time.

17.
Mod Rheumatol Case Rep ; 6(2): 234-238, 2022 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-34878139

RESUMO

A 78-year-old man presented to our hospital with a history of 10 kg weight loss within 6 months previously and general fatigue and fever for 2 and 1 months, respectively. On hospitalisation, the patient was diagnosed with polyarteritis nodosa after multiple microaneurysms were observed in the liver, kidney, pancreas, and mesenteries. He achieved remission with the administration of 1000 mg methylprednisolone for 3 days, followed by prednisolone (55 mg/day). Steroids were successfully tapered with no re-elevation in inflammation. Two months after the administration of steroids, the patient complained of acute abdominal pain and developed severe acute pancreatitis. During treatment for pancreatitis, the patient died due to septic shock and disseminated intravascular coagulation. An autopsy revealed necrotising vasculitis in the intrapancreatic arteries and ischaemia of the downstream arterioles resulting in acute pancreatitis.


Assuntos
Aneurisma , Pancreatite , Poliarterite Nodosa , Doença Aguda , Idoso , Arteríolas , Humanos , Masculino , Metilprednisolona , Pancreatite/complicações , Pancreatite/diagnóstico , Poliarterite Nodosa/complicações , Poliarterite Nodosa/diagnóstico
18.
Front Chem ; 9: 777041, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34888295

RESUMO

Here, we report the photophysical structure-property relationship of porphyrins adsorbed on gold nanoparticles. The number of porphyrin-alkanethiolate adsorbates per particle was adjusted by a post-synthetic thiol/thiolate exchange reaction on 1-dodecanethiolate-protected gold nanoparticles. Even with a low loading level of adsorbates (<10% of all thiolate sites on gold nanoparticles), the shoulder absorption at the Soret band was intensified, indicating the formation of aggregates of porphyrin adsorbates on the nanoparticles. Steady-state fluorescence quantum yields could be adjusted by the bulkiness of substituents at the meso-positions of the porphyrin or the methylene linker chain length, regardless of the porphyrin loading level and the nanoparticle diameter.

19.
Cells ; 10(11)2021 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-34831391

RESUMO

Although high-fat diet (HFD)-related dysbiosis is involved in the development of steatohepatitis, its pathophysiology especially in the small intestine remains unclear. We comprehensively investigated not only the liver pathology but also the microbiome profile, mucosal integrity and luminal environment in the small intestine of mice with HFD-induced obesity. C57BL/6J mice were fed either a normal diet or an HFD, and their small-intestinal contents were subjected to microbial 16S rDNA analysis. Intestinal mucosal permeability was evaluated by FITC-dextran assay. The levels of bile acids in the small-intestinal contents were measured by liquid chromatography/mass spectrometry. The expression of tight junction molecules, antimicrobial peptides, lipopolysaccharide and macrophage marker F4/80 in the small intestine and/or liver was examined by real-time RT-PCR and immunohistochemistry. The abundance of Lactobacillus was markedly increased and that of Clostridium was drastically decreased in the small intestine of mice fed the HFD. The level of conjugated taurocholic acid was significantly increased and those of deconjugated cholic acid/secondary bile acids were conversely decreased in the small-intestinal contents. The expression of occludin, antimicrobial Reg IIIß/γ and IL-22 was significantly decreased in the small intestine of HFD-fed mice, and the intestinal permeability was significantly accelerated. Infiltration of lipopolysaccharide was significantly increased in not only the small-intestinal mucosa but also the liver of HFD-fed mice, and fat drops were apparently accumulated in the liver. Pathophysiological alteration of the luminal environment in the small intestine resulting from a HFD is closely associated with minimal inflammation involving the gut-liver axis through disturbance of small-intestinal mucosal integrity.


Assuntos
Dieta Hiperlipídica , Mucosa Intestinal/patologia , Intestino Delgado/patologia , Fígado/patologia , Animais , Peptídeos Catiônicos Antimicrobianos/metabolismo , Peso Corporal , Citocinas/genética , Citocinas/metabolismo , Microbioma Gastrointestinal , Lipopolissacarídeos/metabolismo , Masculino , Camundongos Endogâmicos C57BL , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas de Junções Íntimas/metabolismo
20.
Biomedicines ; 9(6)2021 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-34204993

RESUMO

Although probiotics may be useful for the treatment of irritable bowel syndrome (IBS), it is unclear how probiotics play a role in colonic mucosal integrity and immunity. Here, we aimed to investigate the effect of Bifidobacterium bifidum G9-1 (BBG9-1) on colonic mucosal integrity and macrophage behavior in rats subjected to maternal separation (MS) as a model of IBS. MS pups were individually separated from their mother rats, and a proportion of the MS rats were orally administered BBG9-1. The colonic mucosal permeability was evaluated by Ussing chamber assay. The expression of tight junction proteins and cytokines and the population of CD80-positive cells was examined in the colonic tissues by real-time reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. Caco2 cells were stimulated with cytokines and the transepithelial electric resistance (TEER) was measured. MS rats showed significantly higher colonic permeability and lower claudin 4 expression in the colonic epithelium relative to controls. The number of CD80-positive macrophages was significantly increased in the colonic mucosa of MS rats, accompanied by the increase of IL-6 and IFN-γ expression. BBG9-1 treatment ameliorated the increase of M1 macrophage and IL-6/IFN-γ expression in the colonic tissue of MS rats. Simultaneously, BBG9-1 treatment improved the enhanced mucosal permeability and the decreased claudin 4 expression in the colon of MS rats. IL-6 and IFN-γ, whose expression is enhanced in the colon of MS rats, significantly decreased TEER in Caco2 cells in vitro. Probiotic BBG9-1 has a preventive effect on the acceleration of colonic permeability and M1 macrophage population in maternally separated rats.

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