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1.
Neuromolecular Med ; 26(1): 16, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38668900

RESUMO

Toll-like receptor (TLR) 7 plays an important role in recognizing virus-derived nucleic acids. TLR7 signaling in astrocytes and microglia is critical for activating immune responses against neurotrophic viruses. Neurons express TLR7, similar to glial cells; however, the role of neuronal TLR7 has not yet been fully elucidated. This study sought to determine whether resiquimod, the TLR7/8 agonist, induces the expression of inflammatory chemokines in SH-SY5Y human neuroblastoma cells. Immunofluorescence microscopy revealed that TLR7 was constitutively expressed in SH-SY5Y cells. Stimulation with resiquimod induced C-C motif chemokine ligand 2 (CCL2) expression, accompanied by the activation of nuclear factor-kappa B (NF-κB) in SH-SY5Y cells. Resiquimod increased mRNA levels of C-X-C motif chemokine ligand 8 (CXCL8) and CXCL10, while the increase was slight at the protein level. Knockdown of NF-κB p65 eliminated resiquimod-induced CCL2 production. This study provides novel evidence that resiquimod has promising therapeutic potential against central nervous system viral infections through its immunostimulatory effects on neurons.


Assuntos
Quimiocina CCL2 , Quimiocina CXCL10 , Imidazóis , Interleucina-8 , Receptor 7 Toll-Like , Fator de Transcrição RelA , Humanos , Imidazóis/farmacologia , Quimiocina CCL2/genética , Quimiocina CCL2/biossíntese , Linhagem Celular Tumoral , Receptor 7 Toll-Like/agonistas , Receptor 7 Toll-Like/genética , Quimiocina CXCL10/genética , Quimiocina CXCL10/biossíntese , Fator de Transcrição RelA/metabolismo , Fator de Transcrição RelA/genética , Interleucina-8/genética , Interleucina-8/biossíntese , Receptor 8 Toll-Like/agonistas , Receptor 8 Toll-Like/genética , Neuroblastoma , NF-kappa B/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/biossíntese , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/farmacologia , Transdução de Sinais/efeitos dos fármacos
2.
Nutrients ; 16(4)2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38398848

RESUMO

The Japanese diet is a healthy dietary pattern, and the oral or gut microbiota have been identified as the main factors underlying the beneficial effects of the Japanese diet. However, epidemiological studies on Japanese dietary patterns calculated from daily eating habits in the general population yielded inconsistent findings. This study aimed to determine the association between the 12-component modified Japanese Diet Index (mJDI12) and the oral and gut microbiota in the general population of a rural area in Japan. After propensity-score matching, 396 participants (198 each in the low and high mJDI12 groups) were picked out. One year after the follow up survey, we reclassified the subjects and compared the low and high mJDI12 groups again. Participants with a high mJDI12 had a higher relative abundance of butyric acid-producing bacteria in their gut microbiota. Moreover, the significantly higher dietary fiber intake in the high mJDI12 group suggested that the high intake of dietary fiber contributed to an increase in butyric acid-producing bacteria in the gut. In contrast, in individuals with a high mJDI12, only Allpprevotella was decreased in the oral microbiota. Thus, the Japanese dietary pattern can have beneficial effects by improving the oral and gut microbiota.


Assuntos
Microbioma Gastrointestinal , Humanos , Japão , Estudos de Coortes , Ácido Butírico , Fezes/microbiologia , Dieta , Bactérias , Fibras na Dieta
3.
Diagnostics (Basel) ; 13(23)2023 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-38066829

RESUMO

Surgery avoidance is an important goal in Crohn's disease (CD) treatment and predicting the risk of subsequent surgery is important to determine adequate therapeutic strength for patients with newly diagnosed CD. Herein, we aimed to construct a prediction model for the risk of subsequent surgery based on disease characteristics at the patients' initial visit. We retrospectively collected disease characteristic data from 93 patients with newly diagnosed CD. A logistic regression model with a brute force method was used to maximize the area under the receiver operating characteristic curve (auROC) by employing a combination of potential predictors from 14 covariates (16,383). The auROC remained almost constant when one to 12 covariates were considered, reaching a peak of 0.89 at four covariates (small-bowel patency, extensive small-bowel lesions, main lesions, and the number of poor prognostic factors), and it decreased with increasing covariate size. The most significant predictors were small-bowel patency, extensive small-bowel lesions, and age or major lesions. Therefore, this prediction model using covariates may be helpful in determining the likelihood that a patient with newly diagnosed CD will require surgery, which can aid in appropriate treatment selection for high-risk patients.

4.
J Clin Biochem Nutr ; 73(3): 214-220, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37970548

RESUMO

Fibrosis, induced by reactive oxygen species (ROS) production in neutrophils, has harmful effects on the liver and various other organs. However, little is known about the association between liver fibrosis and ROS levels in neutrophils in the general population. This large-scale epidemiological study aimed to determine the association between liver fibrosis and neutrophil-generated ROS levels according to age and sex in the general population. This cross-sectional study included 1,000 participants from a district health promotion project. Participants were grouped based on sex (male; female) and age (young, <65 years; old, ≥65 years). The four groups were as follows: male, young (n = 289); male, old (n = 100); female, young (n = 425); and female, old (n = 186). Liver fibrosis was assessed using the fibrosis 4 (FIB-4) index, aspartate aminotransferase-to-platelet ratio index (APRI), and non-alcoholic fatty liver disease (NAFLD) fibrosis score (NFS). Basal and stimulated ROS were considered in the analysis. Multiple linear analyses showed (1) significant positive correlations between all liver fibrosis scores and basal ROS in the young groups, and (2) significant negative correlations between NFS and stimulated ROS in females. Preventing liver fibrosis through neutrophil-related immune system enhancement may avert the development of lifestyle-related diseases and infections.

5.
Int J Mol Sci ; 24(17)2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37686272

RESUMO

The association between liver fibrosis and oral or gut microbiota has been studied before. However, epidemiological studies in the general population are limited owing to the difficulty of noninvasive liver-fibrosis assessment. FibroScan-asparate aminotransferase (FAST) scores can be used to accurately and non-invasively evaluate liver fibrosis. This study aimed to determine the association between liver fibrosis and oral or gut microbiota using the FAST score in the general population. After propensity score matching of 1059 participants based on sex, age, body mass index, homeostasis model assessment of insulin resistance, and triglyceride levels, 125 (non-liver-fibrosis group, 100; liver fibrosis group, 25) were included. The diversity of gut microbiota differed significantly between the two groups; however, no significant differences were noted in their oral microbiota. The liver fibrosis group showed an increase in the relative abundance of Fusobacteria strains and a decrease in the relative abundance of Faecalibacterium, with the presence of Fusicatenibacter in the gut microbiota. Feacalibacterium was not identified as an independent factor of liver fibrosis in adjusting the fatty liver index. In the general population, gut microbiota may be more involved in liver fibrosis than oral microbiota.


Assuntos
Microbioma Gastrointestinal , Microbiota , Humanos , Aspartato Aminotransferases , População do Leste Asiático , Cirrose Hepática/diagnóstico por imagem
6.
Metabolites ; 13(9)2023 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-37755250

RESUMO

A novel treatment method for achalasia of the esophagus and related disorders is known as peroral endoscopic myotomy (POEM). This study aimed to calculate the resting energy expenditure (REE) and evaluated the degree of physical invasiveness based on metabolic changes during the perioperative period of POEM. Fifty-eight patients who underwent POEM were prospectively enrolled; REE, body weight (BW), and basal energy expenditure were measured on the day of POEM, postoperative day 1 (POD 1), and three days after POEM (POD 3). The median REE/BW increased from 19.6 kcal/kg on the day of POEM to 24.5 kcal/kg on POD 1. On POD 3, it remained elevated at 20.9 kcal/kg. The stress factor on POD 1 was 1.20. Among the factors, including the Eckardt score, operation time, and the length of myotomy, the length of myotomy was associated with changes in REE/BW. During the perioperative period of POEM, the level of variation in energy expenditure was lower than that of esophageal cancer surgeries performed under general anesthesia. However, because the length of myotomy is a factor affecting changes in energy expenditure, careful perioperative management is desirable for patients with longer myotomy lengths.

7.
SAGE Open Med Case Rep ; 11: 2050313X231190493, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37539356

RESUMO

A 51-year-old otherwise healthy woman was referred to our hospital with a fever of unknown origin, liver dysfunction, and anemia. One month prior, she had persistent and spontaneous anterior neck pain, with no exacerbation during swallowing or neck movements. Physical examination revealed no pharyngeal or tonsillar abnormalities, heart murmur, arthritis, skin rash, or lymphadenopathy, except for mild bilateral common carotid artery tenderness at the level of the thyroid cartilage. Blood tests showed nonspecific chronic inflammatory findings, anemia, and liver damage, whereas blood cultures, viral antibodies, interferon-γ release assay, and antibodies specific for any collagen disease showed negative results. Echocardiography and computed tomography without contrast of the neck, chest, abdomen, and pelvis showed no apparent abnormalities. She was subsequently diagnosed with Takayasu arteritis using positron emission tomography. Identifying a characteristic history of bilateral carotid artery tenderness and subsequent positron emission tomography can be useful for diagnosing Takayasu arteritis.

8.
Cancer Chemother Pharmacol ; 92(5): 391-398, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37610625

RESUMO

PURPOSE: This study aims to clarify the impact of CYP3A5 and ABCB1 polymorphisms on the pharmacokinetics of vincristine (VCR) in adult patients receiving CHOP therapy. METHODS: Plasma samples were collected immediately after the end of VCR administration and at 1.5, 2.5, 3.5, 5.5, 9.5, 13.5, and 25.5 h after the start of administration. Areas under the plasma concentration-time curves of VCR in the elimination phase (AUC1.5-25.5) were calculated using the linear trapezoidal rule. Half-lives of VCR during the early phase (1.5-5.5 h) and terminal phase (5.5-25.5 h; t1/2γ) were determined according to the log-linear regression of the concentration-time data for at least 3 sampling points. RESULTS: A total of 41 adult patients were enrolled in this study. The median t1/2γ and AUC1.5-25.5 were significantly longer and higher in CYP3A5 non-expressers (CYP3A5*3/*3) than in CYP3A5 expressers (CYP3A5*1/*1 or *1/*3) (21.3 vs 13.8 h, P = 0.005 and 35.5 vs 30.0 ngï½¥h/mL, P = 0.006, respectively). Conversely, there were no significant differences in pharmacokinetic parameters among the ABCB1 c.1236C>T, c.2677G>A/T, c.3435C>T genotype groups. A stepwise selection multiple linear regression analysis showed that the dose of VCR administered and CYP3A5 non-expresser status were independent factors influencing the AUC1.5-25.5 (partial R2 = 0.212, P = 0.002 and partial R2 = 0.143, P = 0.010, respectively). CONCLUSION: The CYP3A5*3 polymorphism was found to be an indicator for predicting exposure to VCR in adult patients receiving CHOP therapy. This information may be useful for the individualization of VCR dosages.


Assuntos
Citocromo P-450 CYP3A , Adulto , Humanos , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Citocromo P-450 CYP3A/genética , Genótipo , Meia-Vida , Ubiquitina-Proteína Ligases , Vincristina
9.
J Gastroenterol ; 58(10): 1015-1029, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37561155

RESUMO

BACKGROUND: The degree of immune response to COVID-19 vaccination in inflammatory bowel disease (IBD) patients based on actual changes in anti-SARS-CoV-2 antibody titres over time is unknown. METHODS: Data were prospectively acquired at four predetermined time points before and after two vaccine doses in a multicentre observational controlled study. The primary outcome was humoral immune response and vaccination safety in IBD patients. We performed trajectory analysis to identify the degree of immune response and associated factors in IBD patients compared with controls. RESULTS: Overall, 645 IBD patients and 199 control participants were analysed. At 3 months after the second vaccination, the seronegative proportions were 20.3% (combination of anti-tumour necrosis factor [TNF]α and thiopurine) and 70.0% (triple combination including steroids), despite that 80.0% receiving the triple combination therapy were seropositive at 4 weeks after the second vaccination. Trajectory analyses indicated three degrees of change in immune response over time in IBD patients: high (57.7%), medium (35.6%), and persistently low (6.7%). In the control group, there was only one degree, which corresponded with IBD high responders. Older age, combined anti-TNFα and thiopurine (odds ratio [OR], 37.68; 95% confidence interval [CI], 5.64-251.54), steroids (OR, 21.47; 95%CI, 5.47-84.26), and tofacitinib (OR, 10.66; 95%CI, 1.49-76.31) were factors associated with persistently low response. Allergy history (OR, 0.17; 95%CI, 0.04-0.68) was a negatively associated factor. Adverse reactions after the second vaccination were significantly fewer in IBD than controls (31.0% vs 59.8%; p < 0.001). CONCLUSIONS: Most IBD patients showed a sufficient immune response to COVID-19 vaccination regardless of clinical factors. Assessment of changes over time is essential to optimize COVID-19 vaccination, especially in persistently low responders.


Assuntos
COVID-19 , Doenças Inflamatórias Intestinais , Humanos , COVID-19/prevenção & controle , Vacinas contra COVID-19/administração & dosagem , Doenças Inflamatórias Intestinais/tratamento farmacológico , Estudos Prospectivos , Vacinação
10.
Clin Case Rep ; 11(6): e7543, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37323265

RESUMO

Key Clinical Message: Bile duct metastasis of breast cancer is rare. It often causes obstructive jaundice which makes the patient interrupt state of treatment. Endoscopic drainage for obstructive jaundice is effective and less invasive treatment option also in this case. Abstract: A 66-year-old breast ductal carcinoma patient developed obstructive jaundice, presenting with epigastric discomfort and dark-colored urine. Computed tomography and endoscopic retrograde cholangiopancreatography revealed bile duct stenosis. Brushing cytology and tissue biopsy confirmed bile duct metastasis, a self-expandable metallic stent was placed/replaced endoscopically, and chemotherapy was continued, extending the patient's life.

11.
Clin J Gastroenterol ; 16(5): 726-731, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37170062

RESUMO

A 65-year-old woman underwent living-donor liver transplantation (left-lobe graft: GWRW ratio, 0.54) for cirrhosis caused by autoimmune hepatitis. At 68 years, she was diagnosed with obstructive cholangitis due to stricture during a hepaticojejunostomy following impaired liver function. Endoscopic balloon dilation of anastomosis and placement of a plastic stent resulted in improved liver function. However, at 72 years, the patient experienced a flare-up of liver damage. The plastic stent had fallen out, and although endoscopic stenotic dilation was attempted, the anastomotic site was obstructed completely. Therefore, recanalization of the hepaticojejunostomy was attempted using a rendezvous technique. A percutaneous transhepatic biliary drainage tube was inserted through the B3 bile duct, and the complete obstructed anastomosis was confirmed by percutaneous transhepatic and transjejunal approaches. The anastomosis was reopened by excising the scarred tissues from the jejunal side using a 1.5-mm high-frequency knife. A 14-Fr. catheter for the internal fistula tube was percutaneously placed at the opened anastomosis to achieve anastomotic site recanalization. The patient's liver damage improved after the re-internalization, and no symptom recurrence such as obstructive cholangitis developed for 1 year. There are few reports of recanalization of the hepaticojejunostomy with a high-frequency knife. Herein, we report the case with a literature review.


Assuntos
Colangite , Transplante de Fígado , Feminino , Humanos , Idoso , Transplante de Fígado/efeitos adversos , Doadores Vivos , Fígado , Anastomose Cirúrgica/efeitos adversos , Colangite/etiologia , Colangite/cirurgia , Complicações Pós-Operatórias/cirurgia , Stents/efeitos adversos
12.
Sci Rep ; 13(1): 7510, 2023 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-37161081

RESUMO

Narrow band imaging (NBI) has been extensively utilized as a diagnostic tool for colorectal neoplastic lesions. This study aimed to develop a trial deep learning (DL) based four-class classification model for low-grade dysplasia (LGD); high-grade dysplasia or mucosal carcinoma (HGD); superficially invasive submucosal carcinoma (SMs) and deeply invasive submucosal carcinomas (SMd) and evaluate its potential as a diagnostic tool. We collected a total of 1,390 NBI images as the dataset, including 53 LGD, 120 HGD, 20 SMs and 17 SMd. A total of 598,801 patches were trimmed from the lesion and background. A patch-based classification model was built by employing a residual convolutional neural network (CNN) and validated by three-fold cross-validation. The patch-based validation accuracy was 0.876, 0.957, 0.907 and 0.929 in LGD, HGD, SMs and SMd, respectively. The image-level classification algorithm was derived from the patch-based mapping across the entire image domain, attaining accuracies of 0.983, 0.990, 0.964, and 0.992 in LGD, HGD, SMs, and SMd, respectively. Our CNN-based model demonstrated high performance for categorizing the histological grade of dysplasia as well as the depth of invasion in routine colonoscopy, suggesting a potential diagnostic tool with minimal human inputs.


Assuntos
Carcinoma , Neoplasias do Colo , Neoplasias Colorretais , Aprendizado Profundo , Humanos , Imagem de Banda Estreita , Neoplasias do Colo/diagnóstico por imagem , Neoplasias Colorretais/diagnóstico por imagem , Hiperplasia
13.
Nihon Shokakibyo Gakkai Zasshi ; 120(5): 433-440, 2023.
Artigo em Japonês | MEDLINE | ID: mdl-37183037

RESUMO

A 78-year-old female patient with stomach cancer (with hepatic metastasis and peritoneal dissemination) had received eight courses of an S-1 and oxaliplatin regimen as palliative chemotherapy. Computed tomography revealed liver deformities and incidental gastric varices. Esophagogastroduodenoscopy confirmed the findings of gastric varices in the cardia and fornix. It was suspected that oxaliplatin-based chemotherapy had induced non-variceal portal hypertension in the patient-similar to that which is seen in patients with colon cancer who are treated with oxaliplatin-based chemotherapy. We had chosen balloon-occluded retrograde transvenous obliteration (BRTO) for the preventive treatment of gastric varices because the patient had a gastro-renal shunt, which enabled access to the gastric varices via the vena cava. Our patient had undergone BRTO, which resulted in the endoscopic disappearance of gastric varices. Currently, the patient is continuing chemotherapy without bleeding from gastric varices. Our case suggests that patients with gastric cancer treated with oxaliplatin-based chemotherapy require careful follow-up for portal hypertension.


Assuntos
Oclusão com Balão , Varizes Esofágicas e Gástricas , Hipertensão Portal , Neoplasias Gástricas , Feminino , Humanos , Idoso , Varizes Esofágicas e Gástricas/diagnóstico por imagem , Varizes Esofágicas e Gástricas/etiologia , Varizes Esofágicas e Gástricas/terapia , Neoplasias Gástricas/terapia , Neoplasias Gástricas/complicações , Oxaliplatina , Hipertensão Portal/complicações , Resultado do Tratamento , Hemorragia Gastrointestinal/terapia
14.
Int J Mol Sci ; 24(10)2023 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-37240022

RESUMO

Vitamin A ensures intestinal homeostasis, impacting acquired immunity and epithelial barrier function; however, its role in innate immunity is mostly unknown. Here, we studied the impact of vitamin A in different dextran sulfate sodium (DSS)-induced colitis animal models. Interestingly, more severe DSS-induced colitis was observed in vitamin A-deficient (VAD) mice than in vitamin A-sufficient (VAS) mice; the same was observed in VAD severe combined immunodeficient mice lacking T/B cells. Remarkably, IL-1ß production, LC3B-II expression, and inflammasome activity in the lamina propria were significantly elevated in VAD mice. Electron microscopy revealed numerous swollen mitochondria with severely disrupted cristae. In vitro, non-canonical inflammasome signaling-induced pyroptosis, LC3B-II and p62 expression, and mitochondrial superoxide levels were increased in murine macrophages (RAW 264.7) pretreated with retinoic acid receptor antagonist (Ro41-5253). These findings suggest that vitamin A plays a crucial role in the efficient fusion of autophagosomes with lysosomes in colitis.


Assuntos
Colite , Inflamassomos , Animais , Camundongos , Inflamassomos/metabolismo , Vitamina A/farmacologia , Sulfato de Dextrana/toxicidade , Colite/metabolismo , Lisossomos/metabolismo , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças
15.
Int J Hematol ; 118(4): 503-507, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37093551

RESUMO

Anti-SARS-CoV-2 vaccines were developed in response to the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although the BNT162b2 mRNA vaccine is effective, adverse effects have been reported. Here, we report a case of extranodal NK/T-cell lymphoma, nasal type (ENKL), of the left arm following BNT162b2 mRNA vaccination. A 73-year-old male presented with a lump in the left arm, which was the site where he received the BNT162b2 mRNA vaccine 3 months prior. He was treated with topical corticosteroids and debridement, but the tumor progressed. Additionally, fever, night sweats, and general fatigue were observed. Laboratory findings included thrombocytopenia, elevated lactate dehydrogenase, and soluble interleukin-2 receptor levels. Skin biopsy led to a diagnosis of ENKL. The patient was treated with a 50% dose of SMILE therapy and radiotherapy, resulting in regression of the tumor. It seems that latent Epstein-Barr virus (EBV)-infected NK/T cells were reactivated by vaccination and contributed to the onset of ENKL. This is the first report of ENKL after BNT162b2 mRNA vaccination. The present case highlights the possible risk of development of malignant lymphoma, including ENKL at the injection site, after BNT162b2 COVID-19 vaccination.


Assuntos
COVID-19 , Infecções por Vírus Epstein-Barr , Linfoma Extranodal de Células T-NK , Masculino , Humanos , Idoso , Herpesvirus Humano 4/genética , Vacina BNT162 , Vacinas contra COVID-19/efeitos adversos , Braço/patologia , COVID-19/prevenção & controle , COVID-19/complicações , SARS-CoV-2 , Linfoma Extranodal de Células T-NK/terapia
16.
Fukushima J Med Sci ; 69(1): 11-20, 2023 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-36990790

RESUMO

OBJECTIVES: Methotrexate (MTX) is associated with extensive side effects, including myelosuppression, interstitial pneumonia, and infection. It is, therefore, critical to establish whether its administration is required after achieving remission with tocilizumab (TCZ) and MTX combination therapy in patients with rheumatoid arthritis (RA). Therefore, the aim of this multicenter, observational, cohort study was to evaluate the feasibility of MTX discontinuation for the safety of these patients. METHODS: Patients with RA were administered TCZ, with or without MTX, for 3 years; those who received TCZ+MTX combination therapy were selected. After remission was achieved, MTX was discontinued without flare development in one group (discontinued [DISC] group, n = 33) and continued without flare development in another group (maintain [MAIN] group, n = 37). The clinical efficacy of TCZ+MTX therapy, patient background characteristics, and adverse events were compared between groups. RESULTS: The disease activity score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR) at 3, 6, and 9 months was significantly lower in the DISC group (P < .05, P < .01, and P < .01, respectively). Further, the DAS28-ESR remission rate at 6 and 9 months and Boolean remission rate at 6 months were significantly higher in the DISC group (P < .01 for all). Disease duration was significantly longer in the DISC group (P < .05). Furthermore, the number of patients with stage 4 RA was significantly higher in the DISC group (P < .01). CONCLUSIONS: Once remission was achieved, MTX was discontinued in patients who responded favorably to TCZ+MTX therapy, despite the prolonged disease duration and stage progression.


Assuntos
Antirreumáticos , Artrite Reumatoide , Humanos , Metotrexato/efeitos adversos , Antirreumáticos/efeitos adversos , Estudos de Coortes , Estudos de Viabilidade , Quimioterapia Combinada , Artrite Reumatoide/tratamento farmacológico , Resultado do Tratamento
17.
Exp Ther Med ; 25(3): 112, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36793327

RESUMO

Dietary fat strongly influences the intestinal mucosal barrier, which protects against invading pathogenic bacteria. A high-fat diet (HFD) compromises the integrity of epithelial tight junctions (TJs) and reduces mucin production, leading to intestinal barrier disruption and metabolic endotoxemia. It has been shown that the active constituents of indigo plants can protect against intestinal inflammation; however, their protective role in HFD-induced intestinal epithelial damage remains unknown. The present study aimed to investigate the effects of Polygonum tinctorium leaf extract (indigo Ex) on HFD-induced intestinal damage in mice. Male C57BL6/J mice were fed a HFD and injected intraperitoneally with either indigo Ex or phosphate-buffered saline (PBS) for 4 weeks. The expression levels of TJ proteins, zonula occludens-1 and Claudin-1, were analyzed by immunofluorescence staining and western blotting. The colon mRNA expression levels of tumor necrosis factor-α, interleukin (IL)-12p40, IL-10 and IL-22 were measured by reverse transcription-quantitative PCR. The results revealed that indigo Ex administration attenuated the HFD-induced shortening of the colon. Colon crypt length was shown to be significantly greater in the indigo Ex-treated group mice compared with that in the PBS-treated group mice. Moreover, indigo Ex administration increased the number of goblet cells, and ameliorated the redistribution of TJ proteins. Notably, indigo Ex significantly increased the colon mRNA expression levels of IL-10. Indigo Ex displayed little effect on the gut microbial composition of HFD-fed mice. Taken together, these results suggested that indigo Ex may protect against HFD-induced epithelial damage. The leaves of indigo plants contain promising natural therapeutic compounds that could be used to treat obesity-associated intestinal damage and metabolic inflammation.

18.
Diagnostics (Basel) ; 13(4)2023 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-36832114

RESUMO

Recently, the importance of achieving clinical and deep remissions with mucosal healing (MH) has been demonstrated as a therapeutic goal to avoid Crohn's disease (CD) surgical operations. Although ileocolonoscopy (CS) is considered the gold standard, there are increasing reports on the benefits of capsule endoscopy (CE) and serum leucine-rich α2-glycoprotein (LRG) for evaluating small-bowel lesions in CD. We evaluated the data of 20 patients with CD who underwent CE in our department between July 2020 and June 2021 and whose serum LRG level was measured within 2 months. Concerning the mean LRG value, there was no significant difference between the CS-MH and CS-non-MH groups. Conversely, the mean LRG level was 10.0 µg/mL in seven patients in the CE-MH group and 15.2 µg/mL in 11 patients in the CE-non-MH group with a significant difference between the two groups (p = 0.0025). This study's findings show that CE can sufficiently determine total MH in most cases, and LRG is useful for evaluating CD small-bowel MH because of its correlation with CE-MH. Furthermore, satisfying CS-MH criteria and a cut-off value of 13.4 µg/mL for LRG suggests its usefulness as a CD small-bowel MH marker, which could be incorporated into the treat-to-target strategy.

19.
J Gastroenterol ; 58(3): 205-216, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36607399

RESUMO

BACKGROUND: Given the increasing health concerns for patients with inflammatory bowel disease (IBD), amidst the COVID-19 pandemic, we investigated the impact of the pandemic on the anxiety and behavioral changes in Japanese patients with IBD. METHODS: We analyzed 3032 questionnaires from patients with IBD, aged 16 years or older visiting 30 hospitals and 1 clinic between March 2020 and June 2021. The primary outcome was the score of the anxiety experienced by patients with IBD during the pandemic. RESULTS: Participants reported a median age of 44 years; 43.3% of the patients were women. Moreover, 60.6% and 39.4% were diagnosed with ulcerative colitis and Crohn's disease, respectively, with a median disease duration of 10 years. Participants indicated an average of disease-related anxiety score of 5.1 ± 2.5 on a ten-point scale, with a tendency to increase, 1 month after the number of infected persons per population increased. The top three causes for anxiety were the risk of contracting COVID-19 during hospital visits, SARS-CoV-2 infection due to IBD, and infection by IBD medication. Factors associated with anxiety were gender (women), being a homemaker, hospital visit timings, mode of transportation (train), use of immunosuppressive drugs, and nutritional therapy. Most patients continued attending their scheduled hospital visits, taking their medications, experienced the need for a family doctor, and sought guidance and information regarding COVID-19 from primary doctors, television, and Internet news. CONCLUSIONS: Patients with IBD experienced moderate disease-related anxiety due to the pandemic and should be proactively informed about infectious diseases to relieve their anxiety.


Assuntos
COVID-19 , Doenças Inflamatórias Intestinais , Adulto , Feminino , Humanos , Masculino , Ansiedade/epidemiologia , Ansiedade/etiologia , COVID-19/epidemiologia , População do Leste Asiático , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/terapia , Pandemias
20.
DEN Open ; 3(1): e209, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36714062

RESUMO

Objectives: Gastrointestinal endoscopy increases the risk of bacterial exposure to endoscopists. However, before 2019, most endoscopists did not pay attention to microorganism transmission from patients. This study aimed to investigate the incidence of bacterial exposure to endoscopists' faces during gastrointestinal endoscopic procedures using the bacterial culture method. Methods: This was a single-centered, retrospective study including endoscopists who performed various gastrointestinal endoscopy procedures at the Division of Endoscopy, Hirosaki University Hospital between August 31 and October 6, 2020. Endoscopists wore surgical masks and affixed pre-sterilized films over them. Following the gastrointestinal endoscopic procedures, attached microbes were collected from the endoscopists' surface films using sterilized swabs. Collected microorganisms were cultured on tryptic soy agar and 5% sheep blood agar, and the incidence of bacterial exposure was determined by bacterial culture positivity. Cultured bacteria were identified by gram staining and 16S rRNA gene sequencing. Results: Bacterial culture positivity was 12.6%, and it was significantly higher in therapeutic than in diagnostic endoscopy. Notably, therapeutic endoscopy increased bacterial culture positivity in colonoscopy, but not in esophagogastroduodenoscopy. Staphylococci, including Staphylococcus epidermidis and Staphylococcus capitis, were the most commonly found bacteria in samples identified through 16S rRNA gene sequencing. Conclusions: The risk of bacterial exposure to the endoscopist's face was increased in colonoscopy treatment procedures. Therefore, endoscopists should be aware of the significant risk of microbial infection from scattering fluid that comes from the endoscopy's working channel.

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