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1.
BMC Infect Dis ; 22(1): 740, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36114527

RESUMO

BACKGROUND: Basidiobolus ranarum belongs to the Entomophthorales order and the Zygomycetes class. This fungus is an environmental saprophyte that can be found in soil and rotting vegetables.Primarily restricted to tropical regions including Asia, Africa, and South America. It might cause chronic inflammatory diseases, mostly affect subcutaneous tissue. Systemic infections involving the gastrointestinal tract are extremely rare. CASE PRESENTATION: Herein, we present a 44-year-old Persian man with the past medical history of lupus erythematosus with colicky abdominal pain started from three months before admission with many vomiting episodes, and a mass on the right lower quadrant, who had been thought initially to have an abdominal malignancy. The patient had vital signs were within normal ranges. His physical examination revealed tenderness and rebound tenderness on the right lower quadrant of the abdomen. A fixed mass 10 × 10 centimeter in diameter was palpated in the same quadrant. Laboratory, radiologic, colonoscopic examination was requested. The patient underwent laparotomy which revealed a mass in the terminal ileum and ascending colon with retroperitoneal adhesion and invasion to the right ureter behind it. Pathologic examination showed basidiobolomycosis infection in the specimen. CONCLUSION: Fungal infection should be among the differential diagnoses for adults present with abdominal mass in endemic regions of the world.


Assuntos
Lúpus Eritematoso Sistêmico , Zigomicose , Dor Abdominal , Adulto , Colo/patologia , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Masculino , Zigomicose/complicações , Zigomicose/diagnóstico
2.
Mol Med ; 28(1): 104, 2022 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-36058917

RESUMO

BACKGROUND: Inflammatory bowel disease (IBD) is a common chronic remitting disease with no satisfactory treatment. The aim of this study was to investigate the protective effect of α7 nicotinic acetylcholine receptor (α7nAChR), and to determine the underlying mechanism of its activity. METHODS: The expression and distribution of α7nAChR in the intestinal tissue of patients with ulcerative colitis and Crohn's disease were analyzed. The effects of vagal excitation on murine experimental colitis were investigated. The colitis model was induced in C57BL/6 mice by the administration of 3% dextran sulfate sodium (DSS). The therapeutic group received treatment with the α7nAChR agonist PNU-282987 by intraperitoneal injection. RESULTS: Our results showed that there was significantly increased expression of α7nAChR in colitis and Crohn's disease intestinal tissue, and its expression was mainly located in macrophages and neutrophils, which were extensively infiltrated in the disease status. Treatment with an α7nAChR agonist potently ameliorated the DSS-induced illness state, including weight loss, stool consistency, bleeding, colon shortening, and colon histological injury. α7nAChR agonist exerted anti-inflammatory effects in DSS colitis mice by suppressing the secretion of multiple types of proinflammatory factors, such as IL6, TNFα, and IL1ß, and it also inhibited the colonic infiltration of inflammatory cells by blocking the DSS-induced overactivation of the NF-κB and MAPK signaling pathways. Mechanistically, activation of α7nAChR decreased the number of infiltrated M1 macrophages in the colitis intestine and inhibited the phagocytosis ability of macrophages, which were activated in response to LPS stimulation. CONCLUSION: Thus, an α7nAChR agonist ameliorated colonic pathology and inflammation in DSS-induced colitis mice by blocking the activation of inflammatory M1 macrophages.


Assuntos
Colite , Doença de Crohn , Animais , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/patologia , Colo/patologia , Doença de Crohn/metabolismo , Doença de Crohn/patologia , Citocinas/metabolismo , Sulfato de Dextrana/efeitos adversos , Sulfato de Dextrana/metabolismo , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Receptor Nicotínico de Acetilcolina alfa7/metabolismo
3.
Wei Sheng Yan Jiu ; 51(4): 624-644, 2022 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-36047269

RESUMO

OBJECTIVE: To explore the protective effect and mechanism of Bifidobacterium bifidum TMC3115 of improving the gut microbiota disorder caused by antibiotic exposurein early life, and the possible protection of inflammatory bowel disease in adulthood in mice. METHODS: 80 newborn mice were randomly divided into 3 groups, a blank control group(n=40), a ceftriaxone exposure group(n=20), a Bifidobacterium bifidum TMC3115 intervention group(n=20). After birth, they were respectively treated with saline, ceftriaxone(100 mg/kg), and ceftriaxone(100 mg/kg) + TMC3115(1×10~9CFU/d) for 3 weeks. After 3 weeks, half of each group was randomly sacrificed, and the rest were normally fed to 6 weeks. At 6 weeks, the blank control group was randomly divided into a negative control group(n=10) and a colitis model group(n=10). The negative control group drunk pure water freely, and the other three groups were added 3% DSS to the drinking water for 4 days to induce colitis. At 6 weeks and 4 days, the remaining mice were sacrificed. The weight change, spleen coefficient, gut microbiota analysis based on second-generation sequencing and serum tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), and interleukin-10(IL-10)levels of the mice at 3 weeks and after DSS intervention were recorded. In addition, the colon length and inflammation pathology score of the mice after DSS intervention were also measured. RESULTS: At 3 weeks, compared with the control, antibiotic exposure in the early life inhibited the weight gain and reduced the diversity and uniformity of the gut microbiota of the mice(P<0.05). The intervention of TMC3115 under antibiotic exposure during this period increased the relative abundance of Bifidobacterium in the intestines(P<0.05), and the effect still existed after DSS stimulation in adulthood, laying the foundation for TMC3115 to exert long-term benefits. After DSS stimulation in adulthood, mice showed significant weight gain inhibition, colon length shorteningand inflammation pathology scoreincrease compared with the negative control(P<0.05), showed the inflammatory bowel disease(IBD)model was successfully constructed. The relative abundance of beneficial bacteria such as Lactobacillus in the Bifidobacterium bifidum TMC3115 intervention group increased compared with the ceftriaxone exposure group(P<0.05), while the relative abundance of harmful bacteria such as Staphylococcus, Clostridium, and Desulfovibrio decreased(P<0.05). Furthermore, the mice exposed to antibiotic in early life produced a stronger immune response, but the mice which received TMC3115 intervention at the same time had a significant decrease in serum TNF-α and IL-6 levels and increase in IL-10 level compared with the mice which only interfered with antibiotics(P<0.05). CONCLUSION: Antibiotic exposure in early life is a negative factor for long-term inflammatory bowel disease, and TMC3115 has preventive significance for long-term inflammatory bowel disease under the background of antibiotic exposure. The mechanism of TMC3115 may be to adjust the gut microbiota and balance the immune system.


Assuntos
Bifidobacterium bifidum , Colite , Doenças Inflamatórias Intestinais , Animais , Antibacterianos , Bifidobacterium bifidum/fisiologia , Ceftriaxona , Colite/induzido quimicamente , Colite/microbiologia , Colo/patologia , Sulfato de Dextrana , Modelos Animais de Doenças , Inflamação , Doenças Inflamatórias Intestinais/patologia , Interleucina-10 , Interleucina-6 , Camundongos , Camundongos Endogâmicos C57BL , Fator de Necrose Tumoral alfa , Aumento de Peso
4.
Taiwan J Obstet Gynecol ; 61(5): 889-895, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36088063

RESUMO

OBJECTIVE: To present a rare case of xanthogranulomatous inflammation (XI) mimicking a uterine sarcoma and invading the ureter and colon. CASE REPORT: A 66-year-old woman presented with lower abdominal pain. Pelvic examination showed tenderness over the lower abdominal region without cervical discharge. Per-rectal examination showed a hard tumor on the posterior uterine wall, while ultrasonography showed a tumor-like mass extending from the posterior uterine wall to the rectum. Magnetic resonance imaging showed signs of endometrial cancer invading the rectum. However, the tumor markers carbohydrate antigen (CA) 125, CA199, and carcinoembryonic antigen were in the normal range. Cystoscopy, panendoscopy, and colonoscopy showed no significant findings. On performing exploratory laparotomy, we observed pus and severe adhesion on the posterior uterine wall and rectum. Hysterectomy, bilateral adnexectomy, colectomy, and partial left ureter resection were performed. The final pathology showed XI. The pus culture revealed Klebsiella pneumonia and PCR revealed nocardiosis. The patient received 2 weeks of antibiotic treatment and was discharged thereafter. CONCLUSION: XI in elderly women is rare, and hence, differential diagnoses should be carefully considered.


Assuntos
Nocardiose , Pneumonia , Ureter , Neoplasias Uterinas , Idoso , Colo/patologia , Feminino , Humanos , Inflamação , Supuração , Ureter/patologia , Neoplasias Uterinas/cirurgia
5.
PLoS Negl Trop Dis ; 16(9): e0010774, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36084127

RESUMO

BACKGROUND: Currently, inflammatory bowel disease (IBD) has become a global chronic idiopathic disease with ever-rising morbidity and prevalence. Accumulating evidence supports the IBD-hygiene hypothesis that helminths and their derivatives have potential therapeutic value for IBD. Clonorchis sinensis (C. sinensis) mainly elicit Th2/Treg-dominated immune responses to maintain long-term parasitism in the host. This study aimed to evaluate the therapeutic effects of cysteine protease (CsCP) and adult crude antigen (CsCA) of C. sinensis, and C. sinensis (Cs) infection on DSS-induced colitis mice. METHODS: BALB/c mice were given 5% DSS daily for 7 days to induce colitis. During this period, mice were treated with rCsCP, CsCA or dexamethasone (DXM) every day, or Cs infection which was established in advance. Changes in body weight, disease activity index (DAI), colon lengths, macroscopic scores, histopathological findings, myeloperoxidase (MPO) activity levels, regulatory T cell (Treg) subset levels, colon gene expression levels, serum cytokine levels, and biochemical indexes were measured. RESULTS: Compared with Cs infection, rCsCP and CsCA alleviated the disease activity of acute colitis more significant without causing abnormal blood biochemical indexes. In comparison, rCsCP was superior to CsCA in attenuating colonic pathological symptoms, enhancing the proportion of Treg cells in spleens and mesenteric lymph nodes, and improving the secretion of inflammatory-related cytokines (e.g., IL-2, IL-4, IL-10 and IL-13) in serum. Combined with RNA-seq data, it was revealed that CsCA might up-regulate the genes related to C-type lectin receptor and intestinal mucosal repair related signal pathways (e.g., Cd209d, F13a1 and Cckbr) to reduce colon inflammation and benefit intestinal mucosal repair. Dissimilarly, rCsCP ameliorated colitis mainly through stimulating innate immunity, such as Toll like receptor (TLR) signaling pathway, down-regulating the expression of inflammatory cytokines (e.g., IL-12b, IL-23r and IL-7), thereby restraining the differentiation of Th1/Th17 cells. CONCLUSIONS: Both rCsCP and CsCA showed good therapeutic effects on the treatment of acute colitis, but rCsCP is a better choice. rCsCP is a safe, effective, readily available and promising therapeutic agent against IBD mainly by activating innate immunity and regulating the IL-12/IL-23r axis.


Assuntos
Clonorchis sinensis , Colite , Cisteína Proteases , Doenças Inflamatórias Intestinais , Animais , Clonorchis sinensis/metabolismo , Colite/induzido quimicamente , Colo/patologia , Cisteína Proteases/genética , Cisteína Proteases/metabolismo , Citocinas/metabolismo , Dexametasona/uso terapêutico , Sulfato de Dextrana/efeitos adversos , Sulfato de Dextrana/metabolismo , Modelos Animais de Doenças , Interleucina-10/metabolismo , Interleucina-12/farmacologia , Interleucina-13/metabolismo , Interleucina-2 , Interleucina-4/metabolismo , Interleucina-7 , Lectinas Tipo C/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Peroxidase/metabolismo , Receptores Toll-Like/metabolismo
6.
Can Vet J ; 63(9): 957-961, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36060480

RESUMO

A 2-year-old castrated male Great Dane crossbreed dog was presented with a history of diarrhea and suspected intussusception. Abdominal ultrasound revealed a colonic-colonic intussusception. The gastrointestinal tract was explored, and an approximately 5-cm intussusception was discovered mid-colon. All other gastrointestinal structures were normal in appearance. The intussusception could not be reduced manually. A colonic resection and anastomosis were performed together with a left-sided incisional colopexy. The dog recovered from surgery and histopathology revealed the intussusception to be secondary to large cell transmural lymphoma. Sections from the surgical margins revealed proliferation of fibrovascular tissue along the serosal surface segmentally, but no neoplastic cells were identified. The dog was subsequently treated with chemotherapy consisting of doxorubicin and prednisone. No evidence of disease recurrence was noted on ultrasound 9 months after surgery. Approximately 2 years after surgery, the dog is noted to be clinically normal at home with no abnormal findings on physical examination. A complete blood (cell) count and chemistry obtained at this time revealed no significant abnormalities besides mild azotemia. Additional restaging was declined by the owner.


Un cas d'intussusception colon-colon chez un chien secondaire à un lymphome traité par résection c olonique et anastomose. Un grand danois croisé mâle castré âgé de 2 ans a été présenté avec des antécédents de diarrhée et une suspicion d'intussusception. L'échographie abdominale a révélé une intussusception colon-colon. Le tractus gastro-intestinal a été exploré et une intussusception d'environ 5 cm a été découverte au milieu du côlon. Toutes les autres structures gastro-intestinales avaient un aspect normal. L'intussusception n'a pas pu être réduite manuellement. Une résection colonique et une anastomose ont été réalisées avec une colopexie incisionnelle du côté gauche. Le chien a récupéré de la chirurgie et de l'histopathologie a révélé que l'intussusception était secondaire à un lymphome transmural à grandes cellules. Des sections des marges chirurgicales ont révélé une prolifération de tissu fibrovasculaire le long de la surface séreuse de manière segmentaire, mais aucune cellule néoplasique n'a été identifiée. Le chien a ensuite été traité par une chimiothérapie composée de doxorubicine et de prednisone. Aucun signe de récidive de la maladie n'a été noté à l'échographie 9 mois après la chirurgie. Environ 2 ans après la chirurgie, le chien est cliniquement normal à la maison sans résultats anormaux à l'examen physique. Une numération sanguine (cellule) complète et l'analyse chimique obtenues à ce moment n'ont révélé aucune anomalie significative outre une légère azotémie. Une nouvelle restadification a été refusée par le propriétaire.(Traduit par Dr Serge Messier).


Assuntos
Neoplasias do Colo , Doenças do Cão , Intussuscepção , Linfoma não Hodgkin , Anastomose Cirúrgica/veterinária , Animais , Colo/patologia , Colo/cirurgia , Neoplasias do Colo/diagnóstico , Neoplasias do Colo/cirurgia , Neoplasias do Colo/veterinária , Doenças do Cão/diagnóstico por imagem , Doenças do Cão/cirurgia , Cães , Intussuscepção/etiologia , Intussuscepção/cirurgia , Intussuscepção/veterinária , Linfoma não Hodgkin/complicações , Linfoma não Hodgkin/veterinária , Masculino , Recidiva Local de Neoplasia/veterinária
7.
Int J Mol Sci ; 23(16)2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-36012393

RESUMO

Inflammatory bowel disease (IBD) is characterized by a chronic and relapsing inflammatory response in the gastrointestinal tract, resulting in severe symptoms such as abdominal pain, vomiting, diarrhea, bloody stools, and weight loss. Currently, there is no cure, and the pharmacological treatment includes drugs that induce and keep the patient in remission, not reversing the underlying pathogenic mechanism. These therapies, in the long term, may cause various side effects and complications, which has increased the need to investigate new, more effective, and safer pharmacological approaches. In preclinical studies, topiramate has demonstrated a potential anti-inflammatory effect by inhibiting the production of several pro-inflammatory cytokines. This study aimed to investigate the effect of topiramate in a chronic TNBS-induced colitis model in rodents. Experimental colitis was induced by four intrarectal administrations of 1% TNBS in female CD-1 mice. Topiramate 10 and 20 mg were administered intraperitoneally for 14 days. Several parameters were evaluated, such as bodyweight, alkaline phosphatase (ALP), fecal hemoglobin, fecal calprotectin, tumor necrosis factor (TNF)-α, and interleukin (IL)-10. Topiramate reduces TNBS-induced colonic damage in a model of chronic experimental colitis and normalizes the stool consistency and anus appearance. Additionally, topiramate significantly reduced the concentration of ALP, fecal hemoglobin, fecal calprotectin, TNF-α, and IL-10, demonstrating it to be a promising pharmacological approach for the treatment of IBD in the future.


Assuntos
Anti-Inflamatórios , Colite , Topiramato , Animais , Anti-Inflamatórios/uso terapêutico , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/patologia , Colo/patologia , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Complexo Antígeno L1 Leucocitário , Camundongos , Topiramato/uso terapêutico , Ácido Trinitrobenzenossulfônico/efeitos adversos , Fator de Necrose Tumoral alfa/metabolismo
8.
PLoS One ; 17(8): e0268954, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36037173

RESUMO

Inflammatory bowel disease (IBD) is a chronic immune-mediated disease of the gastrointestinal tract. While therapies exist, response can be limited within the patient population. Researchers have thus studied mouse models of colitis to further understand pathogenesis and identify new treatment targets. Flow cytometry and RNA-sequencing can phenotype immune populations with single-cell resolution but provide no spatial context. Spatial context may be particularly important in colitis mouse models, due to the simultaneous presence of colonic regions that are involved or uninvolved with disease. These regions can be identified on hematoxylin and eosin (H&E)-stained colonic tissue slides based on the presence of abnormal or normal histology. However, detection of such regions requires expert interpretation by pathologists. This can be a tedious process that may be difficult to perform consistently across experiments. To this end, we trained a deep learning model to detect 'Involved' and 'Uninvolved' regions from H&E-stained colonic tissue slides. Our model was trained on specimens from controls and three mouse models of colitis-the dextran sodium sulfate (DSS) chemical induction model, the recently established intestinal epithelium-specific, inducible Klf5ΔIND (Villin-CreERT2;Klf5fl/fl) genetic model, and one that combines both induction methods. Image patches predicted to be 'Involved' and 'Uninvolved' were extracted across mice to cluster and identify histological classes. We quantified the proportion of 'Uninvolved' patches and 'Involved' patch classes in murine swiss-rolled colons. Furthermore, we trained linear determinant analysis classifiers on these patch proportions to predict mouse model and clinical score bins in a prospectively treated cohort of mice. Such a pipeline has the potential to reveal histological links and improve synergy between various colitis mouse model studies to identify new therapeutic targets and pathophysiological mechanisms.


Assuntos
Colite , Aprendizado Profundo , Animais , Colo/patologia , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Humanos , Camundongos , Camundongos Endogâmicos C57BL
9.
Mol Brain ; 15(1): 74, 2022 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-36038926

RESUMO

Accumulating evidence has shown that intestinal inflammations in inflammatory bowel disease (IBD) also drive pathological responses in organs outside the intestine, including the brain. Previous studies using the dextran sodium sulfate (DSS)-induced colitis model have shown that colonic inflammation contributes to the development of anxiety- and depression-related behaviors; however, little is known about whether memory function is affected. Here, we subjected male and female C57BL/6J mice to DSS-induced colitis for 6 days, followed by Pavlovian conditioned fear (CF) tests 15 days after the start of inflammation, when local colonic inflammation has receded. The contextual and cued CF tests were used to assess associative fear memory. We found that DSS-induced colitis led to significant impairment in contextual fear memory in both male and female mice; on the other hand, auditory cued fear memories were comparable between control and DSS-treated mice. There were marked signs of astrogliosis in the hippocampal regions 17 days (D17) after colitis induction. Furthermore, molecular characterization of hippocampi showed marked but transient increases in the expression of inflammatory genes Nfkb, Trem2 (microglial marker), GFAP (astrocyte marker), Il1b, and S100a8 in DSS-treated mice. While the expression of Nfkb, Trem2, and GFAP showed a peak on day 10, the S100a8 expression was high on days 10 and 17 and subsided on day 42. Interestingly, expression of Bdnf remained elevated in the times assessed (D10, 17, 42). Together, these results demonstrated that DSS-induced colitis could induce prolonged neuroinflammation and impaired contextual fear memory.


Assuntos
Colite , Animais , Colite/complicações , Colo/patologia , Sulfato de Dextrana , Modelos Animais de Doenças , Medo , Feminino , Inflamação/patologia , Masculino , Glicoproteínas de Membrana , Memória , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B , Receptores Imunológicos
10.
Anticancer Res ; 42(9): 4493-4497, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36039461

RESUMO

BACKGROUND/AIM: To report the frequency of crypts in asymmetric branching (CAB) in biopsies from all colorectal segments in patients with ulcerative colitis in remission (UCR). PATIENTS AND METHODS: Biopsies in 100 UC patients were investigated: 50 with UCR and 50 with ongoing long-lasting UC (LLU; i.e., controls). RESULTS: The frequency of CAB was significantly lower in UCR than in LLUC, both in the right colon and left colorectum. CAB frequency was not influenced by two important confounders: the age and sex of patients. CONCLUSION: CAB is a pathologic aberration of colorectal cryptogenesis evoked by chronic mucosal inflammation. When chronic inflammation waned in UCR, the production of CAB plummeted or ceased. Chronic inflammation and protracted disease-duration in LLUC increase the risk for colorectal dysplasia or carcinoma. Importantly, dysplastic CAB were recently detected in LLUC-associated dysplasia. Whether the abrogation of CAB is instrumental in reducing the neoplastic risk in UCR patients, deserves further investigation.


Assuntos
Colite Ulcerativa , Neoplasias Colorretais , Biópsia , Colite Ulcerativa/patologia , Colo/patologia , Neoplasias Colorretais/patologia , Humanos , Hiperplasia/patologia , Inflamação/patologia
11.
Acta Cir Bras ; 37(5): e370505, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35976342

RESUMO

PURPOSE: To investigate the effects of Periplaneta americana L. on ulcerative colitis (UC) induced by a combination of chronic stress (CS) and 2,4,6-trinitrobenzene sulfonic acid enema (TNBS) in rats. METHODS: The experiment UC model with CS was established in rats by a combination of chronic restraint stress, excess failure, improper, and TNBS. The body weight, disease activity index (DAI), colonic mucosal injury index (CMDI), histopathological score (HS) and pro-inflammatory mediators were measured. The content of corticotropin-releasing hormone (CRH) in hypothalamus or adrenocorticotropic hormone (ACTH) and corticosteroids (CORT) in plasma were evaluated by enzyme-linked immunosorbent assay. The proportion of T lymphocyte subsets was detected by flow cytometry, and gut microbiota was detected by 16S rDNA amplicon sequencing. RESULTS: Weight loss, DAI, CMDI, HS and proinflammatory mediators were reversed in rats by P. americana L. treatment after UC with CS. Increased epidermal growth factor (EGF) was observed in P. americana L. groups. In addition, P. americana L. could reduce the content of CRH and ACTH and regulate the ratio of CD3+, CD3+CD8+ and CD3+CD4+CD25+/CD4+ in spleen. Comparably, P. americana L. changes composition of gut microbiota. CONCLUSIONS: The ethanol extract of Periplaneta Americana L. improves UC induced by a combination of CS and TNBS in rats.


Assuntos
Colite Ulcerativa , Colite , Periplaneta , Hormônio Adrenocorticotrópico/metabolismo , Hormônio Adrenocorticotrópico/farmacologia , Hormônio Adrenocorticotrópico/uso terapêutico , Animais , Colite/patologia , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colo/patologia , Modelos Animais de Doenças , Enema , Etanol/farmacologia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ratos , Ácido Trinitrobenzenossulfônico/metabolismo
12.
Acta Cir Bras ; 37(6): e370602, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35976279

RESUMO

PURPOSE: To examine the effects of a negatively charged nanostructured curcumin microemulsion in experimental ulcerative colitis (UC) in rats. METHODS: Four percent acetic acid was used to induce UC. The animals were treated for seven days and randomly assigned to four groups: normal control (NC), colitis/normal saline (COL/NS), colitis/curcumin (COL/CUR), and colitis/mesalazine (COL/MES). The nanostructured curcumin was formulated with a negative zeta potential (-16.70 ± 1.66 mV). Dosage of the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin 1-ß (IL-1ß), interleukin 6 (IL-6), and antioxidant enzymes (catalase, superoxide dismutase, and glutathione peroxidase), macro and microscopic evaluation of the colon tissue were analyzed. RESULTS: The COL/CUR group had a higher level of antioxidant enzymes compared to the COL/MESgroup. The levels of TNF-α, IL-1ß and IL-6 were significantly lower in the colonic tissue of the COL/CUR group rats, when compared to the COL/NS and COL/MES groups (p < 0.001). The presence of ulcers in the colonic mucosa in rats of the COL/NSgroup was significantly higher than in the COL/MES group (p < 0.001). In the NC and COL/CUR groups, there were no ulcers in the colonic mucosa. CONCLUSIONS: The nanostructured microemulsion of curcumin, used orally, positively influenced the results of the treatment of UC in rats. The data also suggests that nanostructured curcumin with negative zeta potential is a promising phytopharmaceutical oral delivery system for UC therapy. Further research needs to be done to better understand the mechanisms of the negatively charged nanostructured curcumin microemulsion in UC therapy.


Assuntos
Colite Ulcerativa , Colite , Curcumina , Animais , Antioxidantes/farmacologia , Colite/patologia , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Colo/patologia , Curcumina/farmacologia , Interleucina-6 , Ratos , Fator de Necrose Tumoral alfa
13.
J Ethnopharmacol ; 298: 115647, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-35987415

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Inflammatory bowel disease (IBD) is pathologically characterized by an immune response accommodative insufficiency and dysbiosis accompanied by persistent epithelial barrier dysfunction, and is divided into ulcerative colitis (UC) and Crohn's disease (CD). Its progression increases the susceptibility to colitis-associated cancer (CAC), as well as other complications. The Xiao-Jian-Zhong (XJZ) formula has a historical application in the clinic to combat gastrointestinal disorders. AIM OF THE STUDY: The investigation aimed to explore the molecular and cellular mechanisms of XJZ. MATERIALS AND METHODS: Dextran sodium sulfate (DSS) was diluted in drinking water and given to mice for a week to establish murine models of experimental colitis, and the XJZ solution was administered for two weeks. Network pharmacology analysis and weighted gene co-expression network analysis (WGCNA) were utilized to predict the therapeutic role of XJZ against UC and CAC. 16S rRNA sequencing and untargeted metabolomics were conducted utilizing murine feces to examine the changes in the microbiome profile. Biochemical experiments were conducted to confirm the predicted functions. RESULTS: XJZ treatment markedly attenuated DSS-induced experimental colitis progression, and the targets were enriched in inflammation, infection, and tumorigenesis, predicted by network pharmacology analysis. Based on The Cancer Genome Atlas (TCGA) database, the XJZ-targets were related to the survival probability in patients with colorectal cancer, underlying a potential therapeutic value in cancer intervention. Moreover, the XJZ therapy successfully rescued the decreased richness and diversity of microbiota, suppressed the potentially pathogenic phenotype of the gut microorganisms, and reversed the declined linoleic acid metabolism and increased cytochrome P450 activity in murine colitis models. Our in-vitro experiments confirmed that the XJZ treatment suppressed Caspase1-dependent pyroptosis and increased peroxisome proliferators-activated receptor-γ(PPAR-γ) expression in the colon, facilitated the alternative activation of macrophages (Mφs), inhibited tumor necrosis factor-α (TNFα)-induced reactive oxygen species (ROS) level in intestinal organoids (IOs), thereby favoring the mucosal healing. CONCLUSION: The XJZ formula is efficacious for colitis by a prompt resolution of inflammation and dysbiosis, and by re-establishing a microbiome profile that favors re-epithelization, and prevents carcinogenesis.


Assuntos
Colite Ulcerativa , Colite , Animais , Colite/induzido quimicamente , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colo/patologia , Sulfato de Dextrana , Modelos Animais de Doenças , Disbiose/metabolismo , Inflamação/patologia , Metabolômica , Camundongos , Camundongos Endogâmicos C57BL , Farmacologia em Rede , RNA Ribossômico 16S
15.
Int Immunopharmacol ; 111: 109108, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35926271

RESUMO

The immunomodulatory function of natural active ingredients has long been a focus of scientific research, with recent hotspots reporting targeted modulation of the follicular helper T cells (Tfh)/regulatory T cells (Treg) balance as an emerging strategy for the treatment of ulcerative colitis (UC). Here, dextran sodium sulfate induced mice UC and Astragalus polysaccharide (APS, 200 mg/kg/day) was administered simultaneously. In this study, APS effectively alleviated colitis in mice by improving survival rate, disease activity index (DAI), the change rate of body weight, colonic length and weight, and histopathological injury of the colon. Moreover, APS regulated the expression of inflammatory cytokines interleukin (IL)-2, IL-6, IL-12p70, IL-23, Tumour necrosis factor (TNF)-ɑ, and transforming growth factor (TGF)-ß1 in colonic tissues of colitis mice. Importantly, APS significantly downregulated Tfh cell and the expression of its related nuclear transcription factors Blimp-1 and Bcl-6, and cytokine IL-21. Meanwhile, APS regulated the differentiation of Tfh subpopulations in colitis mice, with Tfh10 and Tfr significantly upregulated while Tfh1, Tfh17, and Tfh21 significantly downregulated. In addition, APS significantly upregulated Treg cells and the levels of its associated nuclear transcription factor Foxp3, and cytokine IL-10 in colitis mice. In conclusion, APS effectively alleviated UC by reshaping the balance of Tfh/Treg cells.


Assuntos
Astrágalo (Planta) , Colite Ulcerativa , Colite , Animais , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Colo/patologia , Citocinas/metabolismo , Sulfato de Dextrana/farmacologia , Modelos Animais de Doenças , Camundongos , Polissacarídeos/metabolismo , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico , Células T Auxiliares Foliculares , Linfócitos T Reguladores , Células Th17
16.
J Vis Exp ; (185)2022 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-35969074

RESUMO

Gut microbiota dysbiosis is thought to exert a role in the progression of colitis. However, the precise standards for probiotic administration in alleviating colitis remain undefined. Most analysis methods rely on limited diversity and abundance of gut microorganisms. Therefore, observational studies cannot establish causation. In this study, we applied antibiotic-induced pseudo-germ-free mice to investigate the role of gut microbiota in regulating the probiotic effects of Bacillus cereus (B. cereus) on dextran sulfate sodium (DSS)-induced colitis in mice. This process allows for evaluating the bidirectional regulating effect of B. cereus supplementation on health and provides stable and reproducible results. Here, the detailed protocols for B. cereus cultivation, gavage operation, stool collection, and antibiotic clearance treatment on colitis mice are provided. The optimization methods are also applicable for other chronic inflammatory-associated disorders. The results showed that B. cereus administration decreased body weight loss, colon length shortening, disease activity index, and histopathological scores. However, treatment with antibiotics suppressed the positive effect of B. cereus on colitis. These results indicate that gut microbiota are needed for the alleviating effects of B. cereus on colitis. Therefore, exploring the beneficial effects of probiotics in this research is a promising approach for developing novel treatment strategies for alleviating the symptoms of chronic inflammatory-associated disorders.


Assuntos
Colite , Microbioma Gastrointestinal , Animais , Antibacterianos/farmacologia , Bacillus cereus , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colo/patologia , Sulfato de Dextrana , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos C57BL
17.
Mol Med Rep ; 26(4)2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36004485

RESUMO

Ulcerative colitis (UC) is a serious chronic inflammatory bowel disease. Oridonin (Ori) has anti­inflammatory, antibacterial and antitumor activities. The current study aimed to investigate the regulatory role of Ori in UC. BALB/C mice were induced to form a model of UC using dextran sulfate sodium (DSS), after which UC mice received high­(Ori­H) and low­doses of Ori (Ori­L). Subsequently, the length of the colon was measured and hematoxylin and, eosin staining was performed to detect colonic injury. Western blot analysis was performed to detect expression level in tight junction­associated proteins in murine colon tissue. Additionally, myeloperoxidase activity and inflammatory factor concentration were detected in colon tissue using ELISA. TUNEL and western blot assays were also performed to detect cell apoptosis, and the expression level of Sirt1/NF­κB/p53 pathway­related proteins was also determined using western blot analysis. The results revealed that Ori ameliorated clinical symptoms and pathological lesions in mice with DSS­induced UC. Furthermore, Ori protected the integrity of the colonic mucosal barrier, reduced the inflammatory response and decreased oxidative stress levels in mice with DSS­induced UC. Ori treatment also inhibited intestinal mucosal cell apoptosis. These effects may have occurred via the Sirtuin­1/NF­κB/p53 pathway. In conclusion, Ori treatment inhibited DSS­induced inflammatory response, oxidative stress and intestinal mucosal apoptosis in UC mice.


Assuntos
Colite Ulcerativa , Colite , Animais , Colite/patologia , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Colo/patologia , Sulfato de Dextrana , Modelos Animais de Doenças , Diterpenos do Tipo Caurano , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Sirtuína 1/metabolismo , Proteínas de Junções Íntimas/metabolismo , Proteína Supressora de Tumor p53/metabolismo
18.
Biomaterials ; 288: 121707, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35953326

RESUMO

Oral mRNA delivery is a promising yet understudied approach for treating inflammatory bowel disease (IBD). Inspired by the colon-targeting ability of ginger-derived nanoparticles (GDNPs), we reversely engineered lipid nanoparticles that comprise the three major lipids identified in GDNPs. When mixed at the ratio found in GDNPs, the selected lipids (phosphatidic acid, monogalactosyldiacylglycerol, and digalactosyldiacylglycerol; 5:2:3) self-assembled into new lipid nanoparticles (nLNPs) in phosphate-buffered saline. We encapsulated IL-22-mRNA within the nLNPs, as enhanced IL-22 expression in the colon is known to have potent anti-inflammatory efficacy against ulcerative colitis (UC). The IL-22 mRNA-loaded nLNPs (IL-22/nLNPs) were found to be about 200 nm in diameter and have a zeta potential of -18 mV. Oral delivery of IL-22/nLNPs elevated the protein expression level of IL-22 in the colonic mucosa of mice. In a mouse model of acute colitis, mice fed with IL-22/nLNPs experienced an accelerated healing process, as indicated by the recovery of more body weight and colon length as well as reduction of the histological index, colonic MPO activity, fecal lipocalin concentration, and mRNA expression levels of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1ß). Our results suggest that our reversely engineered nLNPs is an excellent mRNA delivery platform for treating ulcerative colitis.


Assuntos
Colite Ulcerativa , Gengibre , Nanopartículas , Animais , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Colo/patologia , Citocinas/metabolismo , Sulfato de Dextrana , Interleucinas , Mucosa Intestinal/metabolismo , Lipídeos/uso terapêutico , Lipossomos , Camundongos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Mensageiro/uso terapêutico
19.
Mol Carcinog ; 61(10): 941-957, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35856887

RESUMO

Dietary rice bran (RB) has shown capacity to influence metabolism by modulation of gut microbiota in individuals at risk for colorectal cancer (CRC), which warranted attention for delineating mechanisms for bidirectional influences and cross-feeding between the host and RB-modified gut microbiota to reduce CRC. Accordingly, in the present study, fermented rice bran (FRB, fermented with a RB responsive microbe Bifidobacterium longum), and non-fermented RB were fed as 10% w/w (diet) to gut microbiota-intactspf or germ-free micegf to investigate comparative efficacy against inflammation-associated azoxymethane/dextran sodium sulfate (AOM/DSS)-induced CRC. Results indicated both microbiota-dependent and independent mechanisms for RB meditated protective efficacy against CRC that was associated with reduced neoplastic lesion size and local-mucosal/systemic inflammation, and restoration of colonic epithelial integrity. Enrichment of beneficial commensals (such as, Clostridiales, Blautia, Roseburia), phenolic metabolites (benzoate and catechol metabolism), and dietary components (ferulic acid-4 sulfate, trigonelline, and salicylate) were correlated with anti-CRC efficacy. Germ-free studies revealed gender-specific physiological variables could differentially impact CRC growth and progression. In the germ-free females, the RB dietary treatment showed a ∼72% reduction in the incidence of colonic epithelial erosion when compared to the ∼40% reduction in FRB-fed micegf . Ex vivo fermentation of RB did not parallel the localized-protective benefits of gut microbial metabolism by RB in damaged colonic tissues. Findings from this study suggest potential needs for safety considerations of fermented fiber rich foods as dietary strategies against severe inflammation-associated colon tumorigenesis (particularly with severe damage to the colonic epithelium).


Assuntos
Bifidobacterium longum , Microbioma Gastrointestinal , Oryza , Animais , Azoximetano/toxicidade , Carcinogênese/patologia , Transformação Celular Neoplásica/patologia , Colo/patologia , Sulfato de Dextrana/toxicidade , Dieta , Modelos Animais de Doenças , Feminino , Inflamação/patologia , Camundongos , Camundongos Endogâmicos C57BL , Oryza/metabolismo
20.
Sci Rep ; 12(1): 11550, 2022 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-35798804

RESUMO

Epithelial alarmins are gaining interest as therapeutic targets for chronic inflammation. The nuclear alarmin interleukin-33 (IL-33) is upregulated in the colonic mucosa of acute ulcerative colitis (UC) and may represent an early instigator of the inflammatory cascade. However, it is not clear what signals drive the expression of IL-33 in the colonic mucosa, nor is the exact role of IL-33 elucidated. We established an ex vivo model using endoscopic colonic biopsies from healthy controls and UC patients. Colonic biopsies exposed to hypo-osmotic medium induced a strong nuclear IL-33 expression in colonic crypts in both healthy controls and UC biopsies. Mucosal IL33 mRNA was also significantly increased following hypo-osmotic stress in healthy controls compared to non-stimulated biopsies (fold change 3.9, p-value < 0.02). We observed a modest induction of IL-33 in response to TGF-beta-1 stimulation, whereas responsiveness to inflammatory cytokines TNF and IFN-gamma was negligible. In conclusion our findings indicate that epithelial IL-33 is induced by hypo-osmotic stress, rather than prototypic proinflammatory cytokines in colonic ex vivo biopsies. This is a novel finding, linking a potent cytokine and alarmin of the innate immune system with cellular stress mechanisms and mucosal inflammation.


Assuntos
Alarminas , Colite Ulcerativa , Interleucina-33 , Pressão Osmótica , Alarminas/metabolismo , Colite Ulcerativa/patologia , Colo/patologia , Citocinas/metabolismo , Humanos , Inflamação/patologia , Interleucina-33/metabolismo , Mucosa Intestinal/metabolismo
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