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1.
An. psicol ; 40(1): 1-11, Ene-Abri, 2024. tab
Artigo em Inglês | IBECS | ID: ibc-229021

RESUMO

A pesar de los descubrimientos recientes, los pacientes con enfermedad inflamatoria intestinal (EII) aún enfrentan desafíos para lograr la remisión. Los objetivos del estudio fueron identificar las características de los pacientes con el Inventario de Personalidad de Freiburg y la intensidad de la enfermedad colónica, comorbilidades que podrían estar relacionadas con la personalidad de los sujetos. Los datos se recopilaron en el período 2019-2020 de 46 pacientes y utilizaron métodos no paramétricos. En comparación con el grupo de control, las escalas de Inhibición, Problemas de salud y Emocionalidad tenían puntuaciones brutas significativamente más altas. Las escalas de Orientación Social, Franqueza y Extraversión tuvieron puntajes brutos significativamente más bajos. El estado de salud fue un factor médico que influyó en la escala de Quejas Somáticas, los pacientes que tenían lesiones o comorbilidades tenían puntuaciones brutas significativamente más altas. Los pacientes que tenían comorbilidades además de la EII tenían puntuaciones brutas considerablemente más altas en la escala de Excitabilidad. Se requieren intervenciones psicoterapéuticas de cambio en la percepción de la vida para abordar la descripción del sufrimiento subjetivo relacionado con molestias físicas (escala de quejas somáticas), una fuerte orientación hacia el rendimiento (escala de tensión), cambios de humor, ansiedad y pesimismo (escala de emocionalidad). Otra intervención es la reconsideración y (re)priorización de valores, como la familia, las relaciones íntimas, los amigos, la salud, el crecimiento, el desarrollo, el trabajo equilibrado, todos los cuales pueden promover una sensación de bienestar y equilibrio.(AU)


Despite recent discoveries, patients with inflammatory bowel disease (IBD) still face challenges with attainment of remission. The objectives of the study were to identify the characteristics of patients with the Freiburg Personality Inventory and the intensity of the intestinal disease, comorbidities that could be related to the personality of the subjects. Data were collected in the period 2019–2020 from 46 patients and used nonparametric methods. Compared to the normative sample, the Inhibitedness, Health Concerns, and Emotionality scales had significantly higher raw scores. The Social Orientation, Frankness, and Extraversionscales had significantly lower raw scores. Health status was a medical factor that influenced the Somatic Complaintsscale, patients who had lesions or comorbidities had significantly higher raw scores. Patients who had comorbidities in addition to IBD had considerably higher raw scores on the Excitability scale. Psychotherapeutic change interventions regarding life perception are required to tackle the description of subjective suffering related to physical inconveniences (Somatic Complaintsscale), a strong orientation toward performance (Strainscale), mood swings, anxiety, and pessimism (Emotionality scale). Another intervention is reconsidering values and (re) prioritization, such as family, intimate relationships, friends, health, growth, development, balanced work, all of which can promote a feeling of well-being and balance.(AU)


Assuntos
Humanos , Masculino , Feminino , Doenças Inflamatórias Intestinais/psicologia , Inventário de Personalidade , Psicoterapia/métodos , Sintomas Afetivos , Doença de Crohn/psicologia , Psicologia , Psicologia Clínica , Medicina do Comportamento , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/terapia , Colite Ulcerativa
2.
Front Endocrinol (Lausanne) ; 15: 1275699, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38313367

RESUMO

Background: Observational studies have indicated associations between type 2 diabetes mellitus (T2DM) and both colorectal cancer (CRC) and inflammatory bowel disease (IBD). However, the underlying causality and biological mechanisms between these associations remains unclear. Methods: We conducted a bidirectional Mendelian randomization (MR) analysis employing summary statistics from genome-wide association studies involving European individuals. The inverse variance weighting (IVW) method was the primary method used to assess causality. Additionally, we applied MR Egger, Weighted median, Simple mode, and Weighted mode to evaluate the robustness of the results. Outliers were identified and eliminated using the MR-PRESSO, while the MR-Egger intercept was used to assess the horizontal pleiotropic effects of single nucleotide polymorphisms (SNPs). The heterogeneity was evaluated using the Cochrane Q test, and sensitivity analysis was performed using leave-one-out method. The F statistic was calculated to evaluate weak instrumental variable bias. Finally, a pilot bioinformatics analysis was conducted to explore the underlying biological mechanisms between T2DM and IBD/UC. Results: The IVW results demonstrated that T2DM significantly reduced risks of IBD (OR=0.885, 95% CI: 0.818-0.958, P=0.002) and ulcerative colitis (UC) (OR=0.887, 95% CI: 0.812-0.968, P=0.007). Although the 95% CIs of MR Egger, Weighted median, Simple mode, and Weighted mode were broad, the majority of their estimates were consistent with the direction of IVW. Despite significant heterogeneity among SNPs, no horizontal pleiotropy was observed. The leave-one-out analysis showed that the causality remained consistent after each SNP was removed, underscoring the reliability of the results. Reverse MR analysis indicated that genetic susceptibility to both CRC and IBD had no significant effect on the relative risk of T2DM. Ten hub genes were identified, which mainly enriched in pathways including maturity onset diabetes of the young, thyroid cancer, gastric acid secretion, longevity regulating pathway, melanogenesis, and pancreatic secretion. Conclusion: The presence of T2DM does not increase the risk of CRC or IBD. Moreover, T2DM might reduce risk of IBD, including UC. Conversely, the occurrence of CRC or IBD does not influence the risk of T2DM. The association between T2DM and IBD/UC may be related to the changes in multiple metabolic pathways and CTLA-4-mediated immune response.


Assuntos
Colite Ulcerativa , Diabetes Mellitus Tipo 2 , Doenças Inflamatórias Intestinais , Humanos , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Reprodutibilidade dos Testes , Doenças Inflamatórias Intestinais/genética , Biologia Computacional
3.
Aging Clin Exp Res ; 36(1): 21, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38319411

RESUMO

BACKGROUND: An association has been identified between inflammatory bowel disease (IBD) and frailty; however, the causal nature of this connection remains uncertain. We consequently conducted a two-sample Mendelian randomization (MR) analysis to explore this particular association. METHODS: We acquired distinct datasets for inflammatory bowel disease (IBD), Crohn's disease (CD), ulcerative colitis (UC), and frailty from the published genome-wide association studies (GWAS) database, meticulously selecting instrumental variables (IVs). Subsequently, we employed a bidirection MR to examine the causal relationship between IBD (including CD and UC) and frailty. We utilized statistical methods, with a primary emphasis on inverse-variance weighted (IVW), accompanied by a series of sensitivity analyses to confirm heterogeneity and pleiotropy influenced the outcomes of the MR. RESULTS: We found positive causal effects of genetically increased frailty risk on IBD (OR: 1.015, 95% CI 1.005-1.025, P = 0.004). Furthermore, when scrutinizing specific IBD subtypes, both Crohn's disease (CD) and ulcerative colitis (UC) demonstrated an increased predisposition to frailty (OR: 1.018, 95% CI 1.01-1.027, P < 0.05) and (OR = 1.016, 95% CI 1.005-1.027, P < 0.05). Nevertheless, despite the consistent trends observed in the weighted median and MR-Egger regression analyses for both conditions, statistical significance remained elusive. Notably, the results of the inverse MR analysis did not establish an association between frailty and an elevated risk of IBD development. CONCLUSIONS: Our research indicates that IBD, encompassing both CD and UC, may augment the propensity for frailty. Clinical practitioners must prioritize early frailty assessment in individuals afflicted with inflammatory bowel disease, inclusive of Crohn's disease and ulcerative colitis, facilitating proactive measures and timely interventions. However, our findings do not provide evidence supporting a causal effect of frailty on IBD (including CD and UC). Consequently, further studies are essential to explore the intricate mechanisms that clarify the effect of frailty on IBD.


Assuntos
Colite Ulcerativa , Doença de Crohn , Fragilidade , Doenças Inflamatórias Intestinais , Humanos , Colite Ulcerativa/genética , Doença de Crohn/genética , Fragilidade/genética , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/genética
4.
Int J Nanomedicine ; 19: 993-1016, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38299194

RESUMO

Background: The M1/M2 polarization of intestinal macrophages exerts an essential function in the pathogenesis of ulcerative colitis (UC), which can be adjusted to alleviate the UC symptoms. Purpose: A kind of pH-sensitive lipid calcium phosphate core-shell nanoparticles (NPs), co-loading with dexamethasone (Dex) and its water-soluble salts, dexamethasone sodium phosphate (Dsp), was constructed to comprehensively regulate macrophages in different states towards the M2 phenotype to promote anti-inflammatory effects. Methods: Dex and Dsp were loaded in the outer lipid shell and inner lipid calcium phosphate (Cap) core of the LdCaPd NPs, respectively. Then, the morphology of NPs and methods for determining drug concentration were investigated, followed by in vitro protein adsorption, stability, and release tests. Cell experiments evaluated the cytotoxicity, cellular uptake, and macrophage polarization induction ability of NPs. The in vivo distribution and anti-inflammatory effect of NPs were evaluated through a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced BALB/c mice ulcerative colitis model. Results: The LdCaPd NPs showed a particle size of about 200 nm and achieved considerable loading amounts of Dex and Dsp. The in vitro and in vivo studies revealed that in the acidic UC microenvironment, the cationic lipid shell of LdCaPd underwent protonated dissociation to release Dex first for creating a microenvironment conducive to M2 polarization. Then, the exposed CaP core was further engulfed by M1 macrophages to release Dsp to restrict the pro-inflammatory cytokines production by inhibiting the activation and function of the nuclear factor kappa-B (NF-κB) through activating the GC receptor and the NF kappa B inhibitor α (I-κBα), respectively, ultimately reversing the M1 polarization to promote the anti-inflammatory therapy. Conclusion: The LdCaPd NPs accomplished the sequential release of Dex and Dsp to the UC site and the inflammatory M1 macrophages at this site, promoting the regulation of macrophage polarization to accelerate the remission of UC symptoms.


Assuntos
Colite Ulcerativa , Colite , Nanopartículas , Camundongos , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Colite/induzido quimicamente , Colite/tratamento farmacológico , Macrófagos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Dexametasona/farmacologia , Dexametasona/uso terapêutico , Fosfatos de Cálcio/farmacologia , Lipídeos/efeitos adversos
5.
World J Gastroenterol ; 30(3): 252-267, 2024 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-38314135

RESUMO

BACKGROUND: Ulcerative colitis (UC) is an inflammatory condition with frequent relapse and recurrence. Evidence suggests the involvement of SLC6A14 in UC pathogenesis, but the central regulator remains unknown. AIM: To explore the role of SLC6A14 in UC-associated pyroptosis. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR), immunoblotting, and immunohistochemical were used to assess SLC6A14 in human UC tissues. Lipopolysaccharide (LPS) was used to induce inflammation in FHC and NCM460 cells and model enteritis, and SLC6A14 levels were assessed. Pyroptosis markers were quantified using enzyme-linked immunosorbent assay, Western blotting, and qRT-PCR, and EdU incubation, CCK-8 assays and flow cytometry were used to examine proliferation and apoptosis. Mouse models of UC were used for verification. RESULTS: SLC6A14 was increased and correlated with NLRP3 in UC tissues. LPS-induced FHC and NCM460 cells showed increased SLC6A14 levels. Reducing SLC6A14 increased cell proliferation and suppressed apoptosis. Reducing SLC6A14 decreased pyroptosis-associated proteins (ASC, IL-1ß, IL-18, NLRP3). NLRP3 overexpression counteracted the effects of sh-SLC6A14 on LPS-induced FHC and NCM460 cell pyroptosis. SLC6A14 improved the mucosa in mice with dextran sulfate sodium-induced colitis. CONCLUSION: SLC6A14 promotes UC pyroptosis by regulating NLRP3, suggesting the therapeutic potential of modulating the SLC6A14/NLRP3 axis.


Assuntos
Sistemas de Transporte de Aminoácidos , Colite Ulcerativa , Colite , Proteína 3 que Contém Domínio de Pirina da Família NLR , Animais , Humanos , Camundongos , Sistemas de Transporte de Aminoácidos/genética , Sistemas de Transporte de Aminoácidos/metabolismo , Colite Ulcerativa/induzido quimicamente , Inflamassomos/metabolismo , Lipopolissacarídeos , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Piroptose
6.
Drug Des Devel Ther ; 18: 193-213, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38318501

RESUMO

Ulcer disorders including the oral mucosa, large intestine, and stomach mucosa, cause significant global health burdens. Conventional treatments such as non-steroid anti-inflammatory drugs (NSAIDs), proton pump inhibitors (PPIs), histamine H2 receptor antagonists (H2RAs), and cytoprotective agents have drawbacks like mucosal injury, diminish gastric acid secretion, and interact with concurrent medications. Therefore, alternative therapeutic approaches are needed to tackle this health concern. Plants are rich in active metabolites in the bark, roots, leaves, fruits, and seeds, and have been utilized for medicinal purposes since ancient times. The use of herbal therapy is crucial, and regulations are necessary to ensure the quality of products, particularly in randomized studies, to assess their efficacy and safety in treating ulcer disorders. This study aims to explore the anti-ulcer activity of medicinal plants in treating peptic ulcer disease, ulcerative colitis, and aphthous ulcers. Articles were searched in Scopus and PubMed, and filtered for publication from 2013 to 2023, resulting in a total of 460 from Scopus and 239 from PubMed. The articles were further screened by title and abstract and resulted in 55 articles. Natural products, rich in active metabolites, were described to manage ulcer disease by protecting the mucosa, reducing ulcer effects, inhibiting pro-inflammatory factors, and reducing bacterial load, thus improving patients' quality of life. Natural extracts have proven effective in managing other health problems, including ulcers by reducing pain and decreasing lesions. This review provides an overview of preclinical and clinical studies on medicinal plants, focusing on their effectiveness in treating conditions like peptic ulcers, ulcerative colitis, and aphthous ulcers.


Assuntos
Antiulcerosos , Colite Ulcerativa , Úlcera Péptica , Estomatite Aftosa , Humanos , Úlcera , Colite Ulcerativa/tratamento farmacológico , Estomatite Aftosa/tratamento farmacológico , Qualidade de Vida , Úlcera Péptica/tratamento farmacológico , Antiulcerosos/farmacologia , Antiulcerosos/uso terapêutico , Antagonistas dos Receptores H2 da Histamina , Inibidores da Bomba de Prótons/farmacologia , Inibidores da Bomba de Prótons/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico
7.
BMC Genomics ; 25(1): 130, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38302916

RESUMO

BACKGROUND: Circadian rhythm is crucial to the function of the immune system. Disorders of the circadian rhythm can contribute to inflammatory diseases such as Ulcerative colitis (UC). This Mendelian Randomization (MR) analysis applies genetic tools to represent the aggregated statistical results of exposure to circadian rhythm disorders and UC and its comorbidities, allowing for causal inferences. METHODS: Summary statistics of protein, DNA methylation and gene expression quantitative trait loci in individuals of European ancestry (pQTL, mQTL, and eQTL, respectively) were used. Genetic variants located within or near 152 circadian clock-related genes and closely related to circadian rhythm disorders were selected as instrumental variables. Causal relationships with UC and its comorbidities were then estimated through employed Summary data-based Mendelian Randomization (SMR) and Inverse-Variance-Weighted MR (IVW-MR). RESULTS: Through preliminary SMR analysis, we identified a potential causal relationship between circadian clock-related genes and UC along with its comorbidities, which was further confirmed by IVW-MR analysis. Our study identified strong evidence of positive correlation involving seven overlapping genes (CSNK1E, OPRL1, PIWIL2, RORC, MAX, PPP5C, and AANAT) through MWAS and TWAS in UC, four overlapping genes (OPRL1, CHRNB2, FBXL17, and SIRT1) in UC with PSC, and three overlapping genes (ARNTL, USP7, and KRAS) in UC with arthropathy. CONCLUSIONS: This SMR study demonstrates the causal effect of circadian rhythm disorders in UC and its comorbidities. Furthermore, our investigation pinpointed candidate genes that could potentially serve as drug targets.


Assuntos
Transtornos Cronobiológicos , Relógios Circadianos , Colite Ulcerativa , Humanos , Colite Ulcerativa/genética , Relógios Circadianos/genética , Análise da Randomização Mendeliana , Comorbidade , Estudo de Associação Genômica Ampla , Peptidase 7 Específica de Ubiquitina , Proteínas Argonautas
8.
Eur J Gastroenterol Hepatol ; 36(3): 271-280, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38305113

RESUMO

BACKGROUND: Inflammatory bowel disease (IBD) is associated with chronic intestinal barrier dysfunction, though its non-invasive assessment remains challenging. This study aimed to determine how four putative circulating markers vary across differing states of intestinal inflammation and with therapy in patients with IBD. METHODS: Plasma samples from one prospective cross-sectional and four longitudinal studies, including healthy controls, were analysed for markers of lipopolysaccharide translocation, lipopolysaccharide-binding protein (LBP) and soluble-CD14 (sCD14), and markers of epithelial injury, syndecan-1 and intestinal-type fatty acid-binding protein (IFABP). Inflammatory activity was determined using objective measures. RESULTS: Compared with healthy subjects, concentrations of LBP and sCD14 were higher in patients with active (P < 0.001) and severe ulcerative colitis (UC) (P < 0.0001) and active Crohn's disease (CD) (P < 0.001). In UC in remission, LBP was less than in active disease (P = 0.011) LBP levels decreased longitudinally before and after induction of medical therapy in patients with IBD (P = 0.030) and as severe UC was brought into remission at weeks 2 and 12 (P ≤ 0.022). Response to treatment was associated with higher baseline levels of LBP (P = 0.019) and soluble-CD14 (P = 0.014). Concentrations of syndecan-1 and IFABP were or tended to be lower in UC and CD in active disease and did not change with successful therapy. CONCLUSION: While markers of epithelial injury were subnormal with active disease and did not change with therapy, markers of lipopolysaccharide translocation directly reflected intestinal inflammation, reduced with successful therapy and predicted treatment response.


Assuntos
Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Humanos , Sindecana-1/uso terapêutico , Receptores de Lipopolissacarídeos/uso terapêutico , Lipopolissacarídeos , Estudos Prospectivos , Estudos Transversais , Doenças Inflamatórias Intestinais/complicações , Biomarcadores , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/tratamento farmacológico , Inflamação/complicações
10.
South Med J ; 117(2): 88-92, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38307504

RESUMO

OBJECTIVES: Inflammatory bowel disease (IBD) encompasses Crohn's disease (CD) and ulcerative colitis (UC). These two chronic inflammatory conditions can differ in severity, presentation, and anatomical localization, and can greatly affect quality of life if not managed properly. Given the many healthcare challenges during the coronavirus disease 2019 pandemic, we studied the effects of the pandemic and corresponding changes to medical resources on surgical outcomes for patients with IBD. METHODS: Deidentified data from patients who underwent a colectomy for CD or UC were collected from the National Surgical Quality Improvement Program database of the American College of Surgeons. We analyzed clinical factors and surgical outcomes between 2019 and 2020. RESULTS: Patients with IBD were more likely to have lost >10% of their body mass before the operation in 2020. Operations for patients with UC were significantly shorter in the first year of the pandemic. Patients with CD were less likely to have a urinary tract infection or sepsis postoperatively in 2020, whereas patients with UC were more likely to require a repeat operation. Interestingly, both patient populations were less likely to undergo an emergency operation in 2020 than in 2019. CONCLUSIONS: Colectomy outcomes for patients with CD in 2020 were similar or improved in comparison with those seen in 2019, whereas colectomies for UC saw a statistically but not clinically significant increase in the rate of repeat operations. Overall, these patients seem to have been well managed despite the coronavirus disease 2019 pandemic-induced strain on the healthcare system.


Assuntos
COVID-19 , Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Humanos , Pandemias , Qualidade de Vida , COVID-19/epidemiologia , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/cirurgia , Colite Ulcerativa/cirurgia , Doença de Crohn/epidemiologia , Doença de Crohn/cirurgia , Colectomia
11.
BMC Gastroenterol ; 24(1): 60, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38308210

RESUMO

Ulcerative colitis (UC) is a chronic inflammatory disease that targets the colon and has seen an increasing prevalence worldwide. In our pursuit of new diagnostic and therapeutic approaches for UC, we undertook a sequencing of colons from UC mouse models. We focused on analyzing their differentially expressed genes (DEGs), enriching pathways, and constructing protein-protein interaction (PPI) and Competing Endogenous RNA (ceRNA) networks. Our analysis highlighted novel DEGs such as Tppp3, Saa3, Cemip, Pappa, and Nr1d1. These DEGs predominantly play roles in pathways like cytokine-mediated signaling, extracellular matrix organization, extracellular structure organization, and external encapsulating structure organization. This suggests that the UC pathogenesis is intricately linked to the interactions between immune and non-immune cells with the extracellular matrix (ECM). To corroborate our findings, we also verified certain DEGs through quantitative real-time PCR. Within the PPI network, nodes like Stat3, Il1b, Mmp3, and Lgals3 emerged as significant and were identified to be involved in the crucial cytokine-mediated signaling pathway, which is central to inflammation. Our ceRNA network analysis further brought to light the role of the Smad7 Long non-coding RNA (lncRNA). Key MicroRNA (miRNAs) in the ceRNA network were pinpointed as mmu-miR-17-5p, mmu-miR-93-5p, mmu-miR-20b-5p, mmu-miR-16-5p, and mmu-miR-106a-5p, while central mRNAs included Egln3, Plagl2, Sema7a, Arrdc3, and Stat3. These insights imply that ceRNA networks are influential in UC progression and could provide further clarity on its pathogenesis. In conclusion, this research deepens our understanding of UC pathogenesis and paves the way for potential new diagnostic and therapeutic methods. Nevertheless, to solidify our findings, additional experiments are essential to confirm the roles and molecular interplay of the identified DEGs in UC.


Assuntos
Colite Ulcerativa , MicroRNAs , Animais , Camundongos , Colite Ulcerativa/genética , Intestinos , Inflamação/genética , MicroRNAs/genética , Modelos Animais de Doenças
12.
J Manag Care Spec Pharm ; 30(2): 141-152, 2024 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-38308626

RESUMO

BACKGROUND: Chronic corticosteroid use is common in ulcerative colitis (UC); however, real-world evidence of its burden to the health care system is limited. OBJECTIVE: To quantify chronic corticosteroid use burden in UC. METHODS: Adults with UC initiated on targeted treatments (ie, biologics and advanced/small molecule therapies) or conventional therapy (index date) were selected from a deidentified US insurance claims database (January 1, 2004, to September 30, 2021). Targeted treatments and conventional therapy initiators were stratified into chronic (>90 days corticosteroid use 12 months post-index [landmark]) and nonchronic corticosteroid users. Patient characteristics 12 months pre-index were balanced with inverse probability of treatment weighting. Health care resource use, costs (US$ 2021), and corticosteroid-related complications were compared in the 12 months post-landmark. RESULTS: Targeted treatment initiators included 1,886 chronic and 1,911 nonchronic corticosteroid users; conventional therapy initiators included 4,980 chronic and 5,199 nonchronic users. Chronic vs nonchronic users had 94% more inpatient days and 16% more outpatient visits among targeted treatment initiators, and 135% more inpatient days and 30% more outpatient visits among conventional therapy initiators (all P < 0.01). Mean all-cause total costs per patient per year were $73,491 for chronic vs $58,884 for nonchronic users ($14,607 higher; P < 0.01) for targeted treatment initiators, and $39,335 for chronic vs $21,271 for nonchronic users ($18,065 higher; P < 0.01) for conventional therapy initiators. Odds of infection and bone loss were 14% and 113% higher, respectively, in chronic vs nonchronic users among targeted treatment initiators and 29% and 47% higher in chronic vs nonchronic users among conventional therapy initiators (all P < .01). CONCLUSIONS: The results of this study suggest that chronic corticosteroid use is associated with substantial clinical and economic burden and may indicate unmet needs in the management of UC progression.


Assuntos
Colite Ulcerativa , Adulto , Humanos , Estados Unidos , Colite Ulcerativa/tratamento farmacológico , Estudos Retrospectivos , Corticosteroides/uso terapêutico , Hospitalização , Custos de Cuidados de Saúde
13.
World J Gastroenterol ; 30(3): 280-282, 2024 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-38314128

RESUMO

Inflammatory bowel disease (IBD) is a nonspecific inflammatory disease of the intestine that includes Crohn's disease and ulcerative colitis. Because IBD is difficult to heal and easily relapses, it could worsen patient quality of life and increase economic burdens. Curcumin (CUR) is a bioactive component derived from the rhizome of turmeric (Curcuma longa). Many basic and clinical studies have shown that CUR can efficiently treat IBD by decreasing the activity of proinflammatory cytokines by communicating with transcription factors and signaling molecules. However, due to the limitations of being almost insoluble in aqueous solutions and having low oral bioavailability, it is important to select appropriate pharmaceutical preparations.


Assuntos
Colite Ulcerativa , Doença de Crohn , Curcumina , Doenças Inflamatórias Intestinais , Humanos , Curcumina/uso terapêutico , Qualidade de Vida , Doenças Inflamatórias Intestinais/tratamento farmacológico , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico
14.
Skin Res Technol ; 30(2): e13574, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38303405

RESUMO

BACKGROUND: Mounting evidence suggest that there are an association between psoriasis and ulcerative colitis (UC), although the common pathogeneses are not fully understood. Our study aimed to find potential crucial genes in psoriasis and UC through machine learning and integrated bioinformatics. METHODS: The overlapping differentially expressed genes (DEGs) of the datasets GSE13355 and GSE87466 were identified. Then the functional enrichment analysis was performed. The overlapping genes in LASSO, SVM-RFE and key module in WGCNA were considered as potential crucial genes. The receiver operator characteristic (ROC) curve was used to estimate their diagnostic confidence. The CIBERSORT was conducted to evaluate immune cell infiltration. Finally, the datasets GSE30999 and GSE107499 were retrieved to validate. RESULTS: 112 overlapping DEGs were identified in psoriasis and UC and the functional enrichment analysis revealed they were closely related to the inflammatory and immune response. Eight genes, including S100A9, PI3, KYNU, WNT5A, SERPINB3, CHI3L2, ARNTL2, and SLAMF7, were ultimately identified as potential crucial genes. ROC curves showed they all had high confidence in the test and validation datasets. CIBERSORT analysis indicated there was a correlation between infiltrating immune cells and potential crucial genes. CONCLUSION: In our study, we focused on the comprehensive understanding of pathogeneses in psoriasis and UC. The identification of eight potential crucial genes may contribute to not only understanding the common mechanism, but also identifying occult UC in psoriasis patients, even serving as therapeutic targets in the future.


Assuntos
Quitinases , Colite Ulcerativa , Humanos , Colite Ulcerativa/genética , Aprendizado de Máquina , Biologia Computacional
15.
Eur J Pharm Biopharm ; 196: 114205, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38311187

RESUMO

The targeting and mucoadhesive features of chitosan (CS)-linked solid lipid nanoparticles (SLNs) were exploited to efficiently deliver fexofenadine (FEX) into the colon, forming a novel and potential oral therapeutic option for ulcerative colitis (UC) treatment. Different FEX-CS-SLNs with varied molecular weights of CS were prepared and optimized. Optimized FEX-CS-SLNs exhibited 229 ± 6.08 nm nanometric size, 36.3 ± 3.18 mV zeta potential, 64.9 % EE, and a controlled release profile. FTIR, DSC, and TEM confirmed good drug entrapment and spherical particles. Mucoadhesive properties of FEX-CS-SLNs were investigated through mucin incubation and exhibited considerable mucoadhesion. The protective effect of FEX-pure, FEX-market, and FEX-CS-SLNs against acetic acid-induced ulcerative colitis in rats was examined. Oral administration of FEX-CS-SLNs for 14 days before ulcerative colitis induction reversed UC symptoms and almost restored the intestinal mucosa to normal integrity and inhibited Phosphatidylinositol-3 kinase (73.6 %), protein kinase B (73.28 %), and elevated nuclear factor erythroid 2-related factor 2 (185.9 %) in colonic tissue. Additionally, FEX-CS-SLNs inhibited tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) to (70.79 % & 72.99 %) in colonic tissue. The ameliorative potential of FEX-CS-SLNs outperformed that of FEX-pure and FEX-market. The exceptional protective effect of FEX-CS-SLNs makes it a potentially effective oral system for managing ulcerative colitis.


Assuntos
Quitosana , Colite Ulcerativa , Lipossomos , Nanopartículas , Terfenadina/análogos & derivados , Ratos , Animais , Colite Ulcerativa/tratamento farmacológico , Portadores de Fármacos/efeitos adversos , Tamanho da Partícula
16.
JCI Insight ; 9(3)2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38329124

RESUMO

The role of long noncoding RNAs (lncRNAs) in disease is incompletely understood, but their regulation of inflammation is increasingly appreciated. We addressed the extent of lncRNA involvement in inflammatory bowel disease (IBD) using biopsy-derived RNA-sequencing data from a large cohort of deeply phenotyped patients with IBD. Weighted gene correlation network analysis revealed gene modules of lncRNAs coexpressed with protein-coding genes enriched for biological pathways, correlated with epithelial and immune cell signatures, or correlated with distal colon expression. Correlation of modules with clinical features uncovered a module correlated with disease severity, with an enriched interferon response signature containing the hub lncRNA IRF1-AS1. Connecting genes to IBD-associated single nucleotide polymorphisms (SNPs) revealed an enrichment of SNP-adjacent lncRNAs in biologically relevant modules. Ulcerative colitis-specific SNPs were enriched in distal colon-related modules, suggesting that disease-specific mechanisms may result from altered lncRNA expression. The function of the IBD-associated SNP-adjacent lncRNA IRF1-AS1 was explored in human myeloid cells, and our results suggested IRF1-AS1 promoted optimal production of TNF-α, IL-6, and IL-23. A CRISPR/Cas9-mediated activation screen in THP-1 cells revealed several lncRNAs that modulated LPS-induced TNF-α responses. Overall, this study uncovered the expression patterns of lncRNAs in IBD that identify functional, disease-relevant lncRNAs.


Assuntos
Colite Ulcerativa , RNA Longo não Codificante , Humanos , Redes Reguladoras de Genes , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Fator de Necrose Tumoral alfa/genética , Colite Ulcerativa/genética , Inflamação
17.
Int J Mol Sci ; 25(3)2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38338765

RESUMO

Patients with active ulcerative colitis (UC) display a misalignment of the circadian clock, which plays a vital role in various immune functions. Our aim was to characterize the expression of clock and inflammation genes, and their mutual regulatory genes in treatment-naïve pediatric patients with UC. Using the Inflammatory Bowel Disease Transcriptome and Metatranscriptome Meta-Analysis (IBD TaMMA) platform and R algorithms, we analyzed rectal biopsy transcriptomic data from two cohorts (206 patients with UC vs. 20 healthy controls from the GSE-109142 study, and 43 patients with UC vs. 55 healthy controls from the GSE-117993 study). We compared gene expression levels and correlation of clock genes (BMAL1, CLOCK, PER1, PER2, CRY1, CRY2), inflammatory genes (IκB, IL10, NFκB1, NFκB2, IL6, TNFα) and their mutual regulatory genes (RORα, RORγ, REV-ERBα, PGC1α, PPARα, PPARγ, AMPK, SIRT1) in patients with active UC and healthy controls. The clock genes BMAL1, CLOCK, PER1 and CRY1 and the inflammatory genes IκB, IL10, NFκB1, NFκB2, IL6 and TNFα were significantly upregulated in patients with active UC. The genes encoding the mutual regulators RORα, RORγ, PGC1α, PPARα and PPARγ were significantly downregulated in patients with UC. A uniform pattern of gene expression was found in healthy controls compared to the highly variable expression pattern in patients with UC. Among the healthy controls, inflammatory genes were positively correlated with clock genes and they all showed reduced expression. The difference in gene expression levels was associated with disease severity and endoscopic score but not with histological score. In patients with active UC, clock gene disruption is associated with abnormal mucosal immune response. Disrupted expression of genes encoding clock, inflammation and their mutual regulators together may play a role in active UC.


Assuntos
Colite Ulcerativa , Humanos , Criança , Colite Ulcerativa/genética , Fatores de Transcrição ARNTL/genética , Fator de Necrose Tumoral alfa , Interleucina-10 , Interleucina-6 , PPAR alfa , PPAR gama , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Ritmo Circadiano/fisiologia , Inflamação/genética
18.
Sci Rep ; 14(1): 4314, 2024 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-38383742

RESUMO

The Brazilian Organization for Crohn's Disease and Colitis (GEDIIB) established a national registry of inflammatory bowel disease (IBD). The aim of the study was to identify clinical factors associated with disease severity in IBD patients in Brazil. A population-based risk model aimed at stratifying the severity of IBD based on previous hospitalization, use of biologics, and need for surgery for ulcerative colitis (UC) and Crohn's Disease (CD) and on previous complications for CD. A total of 1179 patients (34.4 ± 14.7y; females 59%) were included: 46.6% with UC, 44.2% with CD, and 0.9% with unclassified IBD (IBD-U). The time from the beginning of the symptoms to diagnosis was 3.85y. In CD, 41.2% of patients presented with ileocolic disease, 32% inflammatory behavior, and 15.5% perianal disease. In UC, 46.3% presented with extensive colitis. Regarding treatment, 68.1%, 67%, and 47.6% received biological therapy, salicylates and immunosuppressors, respectively. Severe disease was associated with the presence of extensive colitis, EIM, male, comorbidities, and familial history of colorectal cancer in patients with UC. The presence of Montreal B2 and B3 behaviors, colonic location, and EIM were associated with CD severity. In conclusion, disease severity was associated with younger age, greater disease extent, and the presence of rheumatic EIM.


Assuntos
Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Feminino , Humanos , Masculino , Doença de Crohn/diagnóstico , Brasil/epidemiologia , Dados de Saúde Coletados Rotineiramente , Doenças Inflamatórias Intestinais/epidemiologia , Colite Ulcerativa/epidemiologia , Colite Ulcerativa/diagnóstico
19.
BMJ Open Gastroenterol ; 11(1)2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38336367

RESUMO

INTRODUCTION: Symptoms, endoscopy and histology have been proposed as therapeutic targets in ulcerative colitis (UC). Observational studies suggest that the achievement of histologic remission may be associated with a lower risk of complications, compared with the achievement of endoscopic remission alone. The actiVE ulcerative colitis, a RanDomIsed Controlled Trial (VERDICT) aims to determine the optimal treatment target in patients with UC. METHODS AND ANALYSIS: In this multicentre, prospective randomised study, 660 patients with moderate to severe UC (Mayo rectal bleeding subscore [RBS] ≥1; Mayo endoscopic score [MES] ≥2) are randomly assigned to three treatment targets: corticosteroid-free symptomatic remission (Mayo RBS=0) (group 1); corticosteroid-free endoscopic remission (MES ≤1) and symptomatic remission (group 2); or corticosteroid-free histologic remission (Geboes score <2B.0), endoscopic remission and symptomatic remission (group 3). Treatment is escalated using vedolizumab according to a treatment algorithm that is dependent on the patient's baseline UC therapy until the target is achieved at weeks 16, 32 or 48. The primary outcome, the time from target achievement to a UC-related complication, will be compared between groups 1 and 3 using a Cox proportional hazards model. ETHICS AND DISSEMINATION: The study was approved by ethics committees at the country level or at individual sites as per individual country requirements. A full list of ethics committees is available on request. Study results will be disseminated in peer-reviewed journals and at scientific meetings. TRIAL REGISTRATION NUMBER: EudraCT: 2019-002485-12; NCT04259138.


Assuntos
Colite Ulcerativa , Humanos , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/diagnóstico , Estudos Prospectivos , Indução de Remissão , Endoscopia Gastrointestinal , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto
20.
BMJ Open Gastroenterol ; 11(1)2024 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-38341192

RESUMO

Inflammatory bowel disease (IBD) treatment was revolutionised with the arrival of biological therapy two decades ago. There are now multiple biologics and increasingly novel small molecules licensed for the treatment of IBD. Treatment guidelines highlight the need for effective control of inflammation and early escalation to advanced therapies to avoid long-term complications. Consequently, a large proportion of patients with IBD receive advanced therapies for a long time. Despite their beneficial risk-benefit profile, these treatments are not without risk of side effects, are costly to healthcare providers and pose a burden to the patient. It is, therefore, paramount to examine in which circumstances a temporary cessation of therapy can be attempted without undue clinical risk. Some patients may benefit from cyclical rather than continuous treatment. This review examines the risk of relapse after discontinuation of advanced therapies, how to identify patients at the lowest risk of relapse and the chance of recapturing response when flaring after discontinuation.


Assuntos
Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Humanos , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Fator de Necrose Tumoral alfa/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Terapia Biológica , Recidiva
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