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A thermosensitive and injectable hydrogel composed of chitosan (CS), chitosan biguanide hydrochloride (CSG) and collagen (CO) could embed umbilical cord mesenchymal stem cells (UC-MSCs), then was applied for the type 2 diabetes mellitus (T2DM) treatment in vivo. UC-MSCs could adhere well on CS/CSG/CO hydrogel surface and cell division could be clearly observed. Especially, UC-MSCs maintained alive till they grew in CS/CSG/CO hydrogel for 8 days, while the amount of UC-MSCs was limited due to the steric hindrance in hydrogel. To T2DM mice contrastive treatment by intraperitoneal injection for thirteen weeks, UC-MSCs + Hydrogel group could improve the impaired glucose tolerance, maintain glucose homeostasis in vivo, and restore islet morphology for T2DM mice. The immunofluorescence staining and western blot experiments further displayed that both the nuclear antigen Ki67 for cell proliferation and pancreatic duodenal homeobox-1 (Pdx1) expression in UC-MSCs + Hydrogel group were significantly higher than the expressions in untreated T2DM group and treated UC-MSCs + PBS group, which indicated that UC-MSCs + Hydrogel elevated ß cell transcriptional activity. Moreover, the positivity rates of iNOS and CD163 in UC-MSCs + Hydrogel group were generally decreased and increased, respectively, compared to those in untreated T2DM group and treated UC-MSCs + PBS group. It displayed that UC-MSCs + Hydrogel could reduce M1 macrophage expression and increase M2 macrophage polarization in T2DM mice.

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BACKGROUND: Emerging evidence has highlighted the therapeutic potential of human umbilical cord mesenchymal stem cells (UC-MSCs) in chemotherapy-induced premature ovarian failure (POF). This study was designed to investigate the appropriate timing and molecular mechanism of UC-MSCs treatment for chemotherapy-induced POF. METHODS: Ovarian structure and function of mice were assessed every 3 days after injections with cyclophosphamide (CTX) and busulfan (BUS). UC-MSCs and UC-MSCs-derived extracellular vesicles (EVs) were infused into mice via the tail vein, respectively. Ovarian function was analyzed by follicle counts, the serum levels of hormones and ovarian morphology. The apoptosis and proliferation of ovarian granulosa cells were analyzed in vitro and in vivo. Label-free quantitative proteomics was used to detect the differentially expressed proteins in UC-MSC-derived EVs. RESULTS: After CTX/BUS injection, we observed that the ovarian function of POF mice was significantly deteriorated on day 9 after CTX/BUS infusion. TUNEL assay indicated that the number of apoptotic cells in the ovaries of POF mice was significantly higher than that in normal mice on day 3 after CTX/BUS injection. Transplantation of UC-MSCs on day 6 after CTX/BUS injection significantly improved ovarian function, enhanced proliferation and inhibited apoptosis of ovarian granulosa cells, whereas the therapeutic effect of UC-MSCs transplantation decreased on day 9, or day 12 after CTX/BUS injection. Moreover, EVs derived from UC-MSCs exerted similar therapeutic effects on POF. UC-MSCs-derived EVs could activate the PI3K/AKT signaling pathway and reduce ovarian granulosa cell apoptosis. Quantitative proteomics analysis revealed that clusterin (CLU) was highly expressed in the EVs of UC-MSCs. The supplementation of CLU proteins prevented ovarian granulosa cells from chemotherapy-induced apoptosis. Further mechanistic analysis showed that CLU-knockdown blocked the PI3K/AKT signaling and reversed the protective effects of UC-MSCs-derived EVs. CONCLUSIONS: Administration of UC-MSCs and UC-MSCs-derived EVs on day 6 of CTX/BUS injection could effectively improve the ovarian function of POF mice. UC-MSCs-derived EVs carrying CLU promoted proliferation and inhibited apoptosis of ovarian granulosa cells through activating the PI3K/AKT pathway. This study identifies a previously unrecognized molecular mechanism of UC-MSCs-mediated protective effects on POF, which pave the way for the use of cell-free therapeutic approach for POF.

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Vesículas Extracelulares , Células Madre Mesenquimatosas , Fosfatidilinositol 3-Quinasas , Insuficiencia Ovárica Primaria , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Cordón Umbilical , Femenino , Animales , Insuficiencia Ovárica Primaria/terapia , Insuficiencia Ovárica Primaria/metabolismo , Insuficiencia Ovárica Primaria/inducido químicamente , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/trasplante , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citología , Ratones , Proteínas Proto-Oncogénicas c-akt/metabolismo , Humanos , Fosfatidilinositol 3-Quinasas/metabolismo , Cordón Umbilical/citología , Clusterina/metabolismo , Apoptosis , Trasplante de Células Madre Mesenquimatosas/métodos , Ovario/metabolismo , Células de la Granulosa/metabolismo , Proliferación Celular , Busulfano/farmacología

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Flavonoid natural products are emerging as a promising approach for treating Ulcerative Colitis (UC) due to their natural origin and minimal toxicity. This study investigates the effects of Neohesperidin (NEO), a natural flavonoid, on Dextran Sodium Sulfate (DSS)-induced UC in mice, focusing on the underlying molecular mechanisms. Early intervention with NEO (25 and 50 mg/kg) mitigated colon shortening, restored damaged barrier proteins, and significantly reduced the inflammatory cytokine levels. Moreover, NEO inhibited the MAPK/NF-κB signaling pathway and enhanced the levels of intestinal barrier proteins (Claudin-3 and ZO-1). Additionally, NEO increased beneficial intestinal probiotics (S24-7 and Lactobacillaceae) while reducing harmful bacteria (Erysipelotrichi, Enterobacteriaceae). Fecal microbial transplantation (FMT) results demonstrated that NEO (50 mg/kg) markedly improved UC symptoms. In conclusion, early NEO intervention may alleviate DSS-induced UC by inhibiting inflammatory responses, preserving intestinal barrier integrity and modulating gut microbiota.

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Colitis Ulcerosa , Sulfato de Dextran , Microbioma Gastrointestinal , Hesperidina , Mucosa Intestinal , Ratones Endogámicos C57BL , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/microbiología , Colitis Ulcerosa/inmunología , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Ratones , Sulfato de Dextran/efectos adversos , Masculino , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/microbiología , Hesperidina/farmacología , Hesperidina/administración & dosificación , Hesperidina/análogos & derivados , Humanos , Bacterias/clasificación , Bacterias/efectos de los fármacos , Bacterias/aislamiento & purificación , Bacterias/genética , FN-kappa B/metabolismo , FN-kappa B/genética , Colon/microbiología , Colon/efectos de los fármacos , Colon/inmunología , Colon/metabolismo , Colon/patología , Modelos Animales de Enfermedad , Inflamación/tratamiento farmacológico

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There is considerable uncertainty regarding the safety and efficacy of biological therapies during pregnancy. We report a case of a 46-year-old female, diagnosed with ulcerative colitis over 30 years ago, who was successfully managed with infliximab and ustekinumab. She experienced no exacerbation of her condition during two pregnancies, demonstrating the safety of biologic therapy in maintaining disease remission during pregnancy. This case report highlights successful outcomes despite the uncertainties associated with biologic therapy during pregnancy and includes a brief review of the relevant literature.

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Ulcerative colitis (UC) is a typical type of inflammatory bowl disease, which is accompanied by an increased risk of depression and anxiety-related psychological symptoms. Betaine is a naturally derived compound that can function as an anti-inflammatory drug and a neuromodulator. In-depth exploration of the potential role of betaine in treating UC-related depression and anxiety is crucial. This study aimed to elucidate the effects of betaine on UC-related depression and anxiety and clarify the underlying mechanisms. A dextran sulfate sodium (DSS)-induced mice model was established by 4% DSS drinking ad libitum for 7 days. The colonic injury was measured using hematoxylin-eosin (HE) staining and Alcian blue-periodic acid Schiff (AB-PAS) staining. Depression and anxiety-like behaviors were separately evaluated using a forced swimming test (FST), a tail suspension test (TST), a light-dark box test (LDBT), and an open field test (OFT). Immunohistochemistry was used to detect DNA damage and neurogenesis in the hippocampus. Western blotting was applied to detect the protein levels of macrophage polarization in mice colons and the alteration of mitochondrial dysfunction and the cGAS-STING pathway in the hippocampus. Betaine strongly alleviated mucosal structural disorder and mucin secretion reduction and promoted M2-macrophage polarization in the colon of DSS-treated mice. In addition, betaine could mitigate depression- and anxiety-like behaviors in DSS-treated mice, reduce the DNA damage and mitochondrial dysfunction, and inhibit the cGAS-STING signaling pathway. Our study reveals the antidepression/anxiety effects of betaine and further demonstrates the potential mechanism by which betaine inhibits DNA damage and mitochondrial dysfunction to block the cGAS-STING pathway, thereby repairing neurogenesis in the hippocampus.

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The gastrointestinal tract is chronically inflamed in ulcerative colitis (UC), which has a complicated etiology involving immunological, environmental, and genetic factors. The inflammatory response that is typical of UC is significantly regulated via the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway. Latest research has displayed that NF-κB signaling is controlled by three main types of non-coding RNAs (ncRNAs): circular RNAs (circRNAs), long non-coding RNAs (lncRNAs), and microRNAs (miRNAs). These ncRNAs can change the expression of key genes within the NF-κB pathway by acting as molecular sponges, transcriptional regulators, and epigenetic modifiers. This review synthesizes current knowledge on the functions by which ncRNAs modulate NF-κB signaling in UC, discusses their potential as biomarkers for disease prognosis and diagnosis, and explores their therapeutic potential. Understanding the intricate interactions between ncRNAs and NF-κB signaling may provide novel insights into UC pathogenesis and targeted therapeutic strategies.

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Background and objective: The use of mesenchymal stem cells for heart failure treatment has gained increasing interest. However, most studies have relied on a single injection approach, with no research yet confirming the effects of multiple administrations. The present trial aims to investigate the safety and efficacy of multi-intravenous infusion of umbilical cord-mesenchymal stem cells (UC-MSCs) in patients with heart failure and reduced ejection fraction (HFrEF). Methods: The PRIME-HFrEF trial is a single-center, prospective, randomized, triple-blinded, placebo-controlled trial of multi-intravenous infusion of UC-MSCs in HFrEF patients. A total of 40 patients meeting the inclusion criteria for HFrEF were enrolled and randomized 1:1 to the MSC group or the placebo group. Patients enrolled will receive intravenous injections of either UC-MSCs or placebo every 6 weeks for three times. Both groups will be followed up for 12 months. The primary safety endpoint is the incidence of serious adverse events. The primary efficacy endpoint is a change in left ventricular ejection fraction (LVEF) measured by left ventricular opacification (LVO) with contrast echocardiography and magnetic resonance imaging (MRI) at 12 months. The secondary endpoints include a composite of the incidence of death and re-hospitalization caused by heart failure at the 12th month, serum NT-proBNP, growth stimulation expressed gene 2 (ST2), and a change of right ventricular structure and function. Conclusions: The PRIME-HFrEF study is designed to shed new light on multiple UC-MSC administration regimens for heart failure treatment.

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Background: Keratoconus is a diseased corneal dilation of unknown etiology. Studies have shown that inflammation may play a role in keratoconus. Inflammatory enteritis (IBD), including ulcerative colitis (UC), is a chronic, systemic inflammatory disease. We used Mendelian randomization to assess the causal relationship among IBD, UC and keratoconus. Methods: The instrumental variable of IBD and UC was selected, the information of the instrumental variable in keratoconus outcome was extracted, and the causal relationship was assessed by the inverse variance weighted method by primary analysis, and its relevant sensitivity analysis. Results: A causal relationship between IBD and keratoconus was observed significantly (P = 0.017, OR = 1.21, 95% CI = 1.03-1.41), and same as to UC and keratoconus (P = 0.038, OR = 1.25, 95% CI = 1.01-1.54). Conclusion: IBD may play a causal role in the development of keratoconus, but the mechanism needs to be further elucidated.

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Background: The subtype of urothelial carcinoma (SUC) has been known to possess morphological diversity for histologic subtype or divergent differentiation. However, the efficacy of avelumab against SUC remains unclear. Therefore, the effect of the treatment as well as the survival results of avelumab monotherapy were evaluated as a first-line therapeutic maintenance in patients with advanced SUC. Methods: A retrospective analysis was conducted on consecutive patients from the Uro-Oncology Group in Kyushu study population with advanced lower and upper urinary tract cancer who underwent avelumab maintenance therapy without progression after first-line platinum-based chemotherapy. Patients with pure urothelial carcinoma (PUC) and SUC were comparatively analyzed based on objective response rate (ORR), disease control rate, progression-free survival (PFS), and overall survival (OS). Results: Out of 49 recorded patients, 38 and 11 had PUC and SUC, respectively. The most common subtype element was glandular differentiation (n=5), followed by squamous differentiation (n=3), micropapillary (n=1), and plasmacytoid subtypes (n=1). The SUC and PUC groups had comparable ORR (0% vs. 2.6%, P>0.99) and disease control rates (54.5% vs. 44.7%, P=0.73). These patient groups also showed no significant difference in PFS (median 3.9 vs. 3.1 months, P=0.33) or OS (median 16.7 vs. 22.1 months, P=0.47). Conclusions: The response of SUC and PUC to avelumab was comparable in patients with advanced lower and upper urinary tract cancer, indicating that avelumab maintenance therapy is also effective for SUC.

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Amateurs often struggle with detecting and quantifying protein biomarkers in body fluids due to the high expertise required. This study introduces a Lab-in-a-Vial (LV) rapid diagnostic platform, featuring hydrangea-like platinum nanozymes (PtNH), for rapid, accurate detection and quantification of protein biomarkers on-site within 15 min. This method significantly enhances detection sensitivity for various biomarkers in body fluids, surpassing traditional methods such as enzyme-linked immunosorbent assays (ELISA) and lateral flow assays (LFA) by ≈250 to 1300 times. The LV platform uses a glass vial coated with specific bioreceptors such as antigens or antibodies, enabling rapid in vitro evaluation of disease risk from small fluid samples, similar to a personal ELISA-like point-of-care test (POCT). It overcomes challenges in on-site biomarker detection, allowing both detection and quantification through a portable wireless spectrometer for healthcare internet of things (H-IoT). The platform's effectiveness and adaptability are confirmed using IgG/IgM antibodies from SARS-CoV-2 infected patients and nuclear matrix protein (NMP22) from urothelial carcinoma (UC) patients as biomarkers. These tests demonstrated its accuracy and flexibility. This approach offers vast potential for diverse disease applications, provided that the relevant protein biomarkers in bodily fluids are identified.

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The nested subtype of urothelial carcinoma (NS-UC), a rare and aggressive bladder cancer, mimics benign bladder lesions but behaves like high-grade urothelial carcinomas. The author reported a rare case of NS-UC, initially presenting with inguinal lymph node metastasis. The tumor cells of NS-UC exhibit minimal cellular atypia, forming small nests, while the tumor cells of lymph node metastatic carcinoma show greater cellular atypia with diverse structures. Immunohistochemistry is helpful in determining the origin of lymph node metastatic carcinoma. NS-UC often presents morphologically similar to benign lesions, which should be given sufficient attention.

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BACKGROUND & AIMS: Treatment options for moderate to severe ulcerative colitis (UC) are increasing rapidly, but the lack of comparative efficacy trials makes treatment choices a clinical challenge. This network-meta-analysis aimed to compare the relative efficacy of biologics and small molecules in achieving remission in patients with moderate to severe UC. METHODS: The literature was searched up to May 2024. Phase 3 placebo or active comparator randomized controlled trials (RCTs) were included. The primary outcome was induction and maintenance of endoscopic improvement (Mayo endoscopic score [MES] ≤1). Secondary outcomes were the induction and maintenance of clinical remission, endoscopic (MES = 0) and histological remission. A sub-analysis was performed based on the RCT design and previous exposure to biologic therapy. RESULTS: We identified 36 studies that met our inclusion criteria, with 14,270 patients with UC. Upadacitinib ranked highest in inducing clinical remission (99.6%), and endoscopic improvement (99.2%), followed by risankizumab (91.4%) and (82.3%) respectively. In maintenance of endoscopic improvement, upadacitinib ranked first (98.6%) followed by filgotinib 200 mg (79.2%). Risankizumab ranked first in the induction of histological remission (89.4%). Followed by guselkumab (88.3%). Upadacitinib ranked first (93.1%) in maintaining histological remission followed by guselkumab (89.5%). CONCLUSION: Upadacitinib appears to be superior to other therapies in achieving clinical remission, endoscopic improvement and remission, and histological remission. Furthermore, novel biologics such as risankizumab and guselkumab ranked high in achieving these outcomes. This study highlights the efficacy of small molecule drugs and novel selective IL-23s as alternatives to other biologics.

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INTRODUCTION: Ulcerative Colitis (UC) is an Inflammatory Bowel Disease (IBD). Surgery is required in cases of severe acute colitis, massive hemorrhage, toxic megacolon, and perforation; in such cases colectomy and JpouchIleoanal anastomosis (IPAA) are performed. The aim of this study was to evaluate functional outcome, and patient satisfaction and Quality of Life (QoL) after surgery. MATERIAL AND METHODS: Questionnaires were administered to 24 patients with UC undergoing surgery from 2011 to 2022. RESULTS: Mean age at IPAA was 10.8 years. Twenty patients underwent IPAA in 3 operations, 4 patients in 2. All patients underwent laparoscopic surgery. 6 months after surgery mean level of satisfaction was 8.7/10, perception of health status was 7.4. Twenty-three patients (95.8%) recommended IPAA. For 20 patients (83.3%) surgery did not cause delay in education, while 14 patients (58.3%) played sport. The lowest number of evacuations was 9.2 per day, the highest 13.3. Seventeen patients (70.8%) had no incontinence and 15 patients (62.5%) were not affected by pouchitis. After 12 months mean satisfaction level raised up to 9.2/10, perception of health status to 8.5. School absences decreased and no other patients showed any delay in education. Seventeen (70.8%) patients played sports. The number of evacuations decreased: the lowest number was 5.1 per day, the highest 7.5. Twenty patients (83.3%) were continent and 12 (50%) did not use antibiotics. CONCLUSION: Most patients show a good functional outcome in defecation frequency and continence, which has improved through time, number of pouchitis episodes has increased. Patients appear satisfied after surgery.

Asunto(s)

Colectomía , Colitis Ulcerosa , Satisfacción del Paciente , Calidad de Vida , Humanos , Colitis Ulcerosa/cirugía , Masculino , Femenino , Niño , Satisfacción del Paciente/estadística & datos numéricos , Adolescente , Colectomía/métodos , Encuestas y Cuestionarios , Anastomosis Quirúrgica/métodos , Proctocolectomía Restauradora/métodos , Resultado del Tratamiento , Preescolar

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Ulcerative colitis (UC) is a chronic inflammatory disorder of the colon, and its pathogenesis remains unclear. Polyamine metabolic enzymes play a crucial role in UC. In this study, we aimed to identify pivotal polyamine-related genes (PRGs) and explore the underlying mechanism between PRGs and the disease status and therapeutic response of UC. We analyzed mRNA-sequencing data and clinical information of UC patients from the GEO database and identified NNMT, PTGS2, TRIM22, TGM2, and PPARG as key PRGs associated with active UC using differential expression analysis and weighted gene co-expression network analysis (WCGNA). Receiver operator characteristic curve (ROC) analysis confirmed the accuracy of these key genes in UC and colitis-associated colon cancer (CAC) diagnosis, and we validated their relationship with therapeutic response in external verification sets. Additionally, single-cell analysis revealed that the key PRGs were specific to certain immune cell types, emphasizing the vital role of intestinal tissue stem cells in active UC. The results were validated in vitro and in vivo experiments, including the colitis mice model and CAC mice model. In conclusion, these key PRGs effectively predict the progression of UC patients and could serve as new pharmacological biomarkers for the therapeutic response of UC.

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Biomarcadores , Colitis Ulcerosa , Poliaminas , Análisis de la Célula Individual , Colitis Ulcerosa/genética , Colitis Ulcerosa/diagnóstico , Colitis Ulcerosa/metabolismo , Colitis Ulcerosa/terapia , Animales , Humanos , Ratones , Biomarcadores/metabolismo , Análisis de la Célula Individual/métodos , Poliaminas/metabolismo , Modelos Animales de Enfermedad , Proteína Glutamina Gamma Glutamiltransferasa 2 , Masculino , Femenino , Neoplasias Asociadas a Colitis/genética , Neoplasias Asociadas a Colitis/patología , Neoplasias Asociadas a Colitis/metabolismo , Transglutaminasas/genética , Transglutaminasas/metabolismo

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Several studies have correlate improved patient outcomes with increased physician-patient contacts, particularly in chronic diseases. Extending this approach to inflammatory bowel disease (IBD) care presents a promising means of improving outcomes. At LSU Health Shreveport (LSUHS), a new approach called "STABILITY" (Symptomatic Review during Biologic Therapy) was implemented during infusion therapy visits for IBD patients. These brief 15 min physician-patient interviews aimed to discuss the patients' current IBD-related symptoms and evaluate the need for any changes in their treatment plan. Our goal was to remove a care gap and prevent intensifying symptoms created by missed appointments and loss of contact. To analyze the effectiveness of the STABILITY approach, a retrospective chart review was conducted on 111 IBD patients (18 with ulcerative colitis, 93 with Crohn's disease) seen at LSUHS between 2011 and 2022. Since March 2019, STABILITY has been mandatory for all infusion therapy visits. The data collected included patients' demographics, lab levels for biomarkers (fecal calprotectin, C-reactive protein, and erythrocyte sedimentation rates), hospitalizations, medication changes, and diagnosis dates before and after the implementation of STABILITY. Additionally, voluntary, anonymous infusion patient satisfaction surveys post-STABILITY were used to gather patient responses. In males with IBD, disease severity and hospitalizations were reduced significantly (p = 0.004 and 0.0234, respectively). In females with IBD, disease severity and hospitalizations were also reduced significantly (p = 0.0001 and 0.0072, respectively). In patients with UC and CD, there were significant improvements in disease severity (p = 0.043 and p = 0.0001, respectively), and CD hospitalizations were also improved (p = 0.0013). In males and females with UC, disease severity was marginally and significantly reduced (p = 0.0781 and p = 0.0379, respectively). In males and females with CD, disease severity was significantly reduced (p = 0.0161 and 0.0003, respectively), and CD male and female hospitalizations were also reduced significantly (p = 0.0436 and 0.013). Analyzing of survey responses, we found that the most patients reported improved IBD symptoms (56%), gained understanding of their condition (84%) and were in favor of continuing STABILITY consultations during infusion therapy (93%). To further investigate the impact of STABILITY, we conducted a comparative analysis between IBD patients undergoing STABILITY infusion therapy and LSUHS patients solely on self-injectable biologics. Our paired data analysis showed significant improvements in disease severity in female IBD patients (1.69 ± 0.13 vs. 1.41 ± 0.12, p = 0.0001) and male IBD patients (1.58 ± 0.16 vs. 1.2 ± 0.135, p = 0.004), in UC patients (1.833 ± 0.4.2 vs. 1.444, p = 0.043), in all CD patients (1.59 ± 0.11 vs. 1.29 ± 0.01, p = 0.0001), in male CD patients (1.52 ± 0.167 vs. 1.15 ± 0.15, p = 0.016), in female CD patients (1.66 ± 0.15 vs. 1.4 ± 0.13, p = 0.0003), in female UC patients (1.82 ± 0.32 vs. 1.45 ± 0.31, p = 0.0379), and marginally in male UC patients (p = 0.0781). Similarly, hospitalizations were significantly reduced in CD patients considered in aggregate (0.21 ± 0.04 vs. 0.11 ± 0.03, p = 0.0013), in male IBD patients (0.175 ± 0.06 vs. 0.05 ± 0.035, p = 0.024), in female IBD patients (0.21 ± 0.05 vs. 0.11 ± 0.04, p = 0.0072), in male CD patients (0.18 ± 0.07 vs. 0.06 ± 0.042, p = 0.0436), and in females with CD (0.23 ± 0.06 vs. 0.13 ± 0.04, p = 0.013). Although average values for fecal calprotectin, CRP, and sedimentation rate were frequently reduced after STABILITY interviews, these data did not reach statistical significance. These preliminary findings suggest that STABILITY may be effective in maintaining low disease activity or remission in IBD patients.

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BACKGROUND: In recent years, significant morbidity and mortality in patients with severe inflammatory bowel disease (IBD) and cytomegalovirus (CMV) have drawn considerable attention to the status of CMV infection in the intestinal mucosa of IBD patients and its role in disease progression. However, there is currently no high-throughput sequencing data for ulcerative colitis patients with CMV infection (CMV + UC), and the immune microenvironment in CMV + UC patients have yet to be explored. METHOD: The xCell algorithm was used for evaluate the immune microenvironment of CMV + UC patients. Then, WGCNA analysis was explored to obtain the co-expression modules between abnormal immune cells and gene level or protein level. Next, three machine learning approach include Random Forest, SVM-rfe, and Lasso were used to filter candidate biomarkers. Finally, Best Subset Selection algorithms was performed to construct the diagnostic model. RESULTS: In this study, we performed transcriptomic and proteomic sequencing on CMV + UC patients to establish a comprehensive immune microenvironment profile and found 11 specific abnormal immune cells in CMV + UC group. After using multi-omics integration algorithms, we identified seven co-expression gene modules and five co-expression protein modules. Subsequently, we utilized various machine learning algorithms to identify key biomarkers with diagnostic efficacy and constructed an early diagnostic model. We identified a total of eight biomarkers (PPP1R12B, CIRBP, CSNK2A2, DNAJB11, PIK3R4, RRBP1, STX5, TMEM214) that play crucial roles in the immune microenvironment of CMV + UC and exhibit superior diagnostic performance for CMV + UC. CONCLUSION: This 8 biomarkers model offers a new paradigm for the diagnosis and treatment of IBD patients post-CMV infection. Further research into this model will be significant for understanding the changes in the host immune microenvironment following CMV infection.

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Ectodermal mesenchymal stem cells-derived conditioned medium (EMSCs-CM) has been reported to protect against ulcerative colitis (UC) in mice, but its underlying mechanism in alleviating UC need to be further elucidated. Here, it is reported that EMSCs-CM could attenuate pro-inflammatory response of LPS-induced IEC-6 cells and regulate the polarization of macrophages towards anti-inflammatory type in vitro. Furthermore, PLGA microspheres prepared by the double emulsion method were constructed for oral delivery of EMSCs-CM (EMSCs-CM-PLGA), which are beneficial for colon-targeted adhesion of EMSCs-CM to the damaged colon mucosa. The results showed that orally-administered of EMSCs-CM-PLGA microspheres reduced inflammatory cells infiltration and maintained the intestinal mucosal barrier. Further investigation found that EMSCs-CM-PLGA microspheres treatment gradually inhibited the activation of NF-κB pathway to regulate M1/M2 polarization balance in colon tissue macrophages, thereby alleviating DSS-induced UC. These results of this study will provide a theoretical basis for clinical application of EMSCs-CM in UC repair.

Asunto(s)

Colitis Ulcerosa , Macrófagos , Células Madre Mesenquimatosas , Microesferas , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Animales , Colitis Ulcerosa/terapia , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/inmunología , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Medios de Cultivo Condicionados/farmacología , Macrófagos/inmunología , Macrófagos/efectos de los fármacos , Ratones , Colon/patología , Colon/efectos de los fármacos , FN-kappa B/metabolismo , Sulfato de Dextran , Masculino , Línea Celular , Mucosa Intestinal/patología , Mucosa Intestinal/inmunología , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efectos de los fármacos , Modelos Animales de Enfermedad , Ratas , Antiinflamatorios/uso terapéutico , Antiinflamatorios/farmacología , Ratones Endogámicos C57BL , Humanos

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Currently, there is no known cause for ulcerative colitis (UC), an inflammatory bowel disease that is difficult to treat. This assay aimed to investigate the protective effects and mechanisms of Dendrobium officinale polysaccharide (DOP) in mice with acute UC induced by dextran sulphate sodium (DSS). We found that DOP could improve weight loss, decrease the disease activity index (DAI), and regulate the release of interleukin 2 (IL-2), IL-4, IL-6, and IL-10 in DSS-induced acute UC mice. Additionally, DOP preserved the integrity of the intestinal barrier in UC mice by increasing goblet cell density and maintaining tight junctions. DOP significantly enhanced total antioxidant capacity (T-AOC), and reduced glutathione (GSH), nitric oxide (NO), and malondialdehyde (MDA) levels in the bloodstream. In terms of serum biochemistry, DOP markedly elevated levels of bilirubin (BIL), alkaline phosphatase (ALP), total bile acid (TBA), creatinine (Crea), and creative kinase isoenzyme (CKMB). Furthermore, DOP increased the relative abundance of Lactobacillales. DOP also improved intestinal health and stimulated the synthesis of potent anti-inflammatory and antiviral substances by regulating the metabolism of purines, prostaglandins, and leukotrienes. Therefore, DOP can be considered a functional dietary supplement for the treatment of UC, as it improves the condition of DSS-induced UC mice.

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Colitis Ulcerosa , Dendrobium , Sulfato de Dextran , Metaboloma , Polisacáridos , Animales , Dendrobium/química , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/metabolismo , Polisacáridos/farmacología , Polisacáridos/química , Sulfato de Dextran/efectos adversos , Ratones , Metaboloma/efectos de los fármacos , Masculino , Microbioma Gastrointestinal/efectos de los fármacos , Citocinas/metabolismo , Antioxidantes/farmacología , Modelos Animales de Enfermedad

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Background Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), presents significant challenges, particularly in pediatric patients. Vitamin D deficiency has been associated with IBD, but its role in disease activity and remission remains unclear. This study investigates the relationship between serum vitamin D levels and IBD markers, including Pediatric Crohn's Disease Activity Index (PCDAI), Pediatric Ulcerative Colitis Activity Index (PUCAI), fecal calprotectin levels, and endoscopy findings. It also explores racial and ethnic disparities in these relationships. Methodology A retrospective study was conducted involving 51 pediatric patients with IBD from the Nemours Children's Health EMR system. Inclusion criteria required documented serum vitamin D levels at diagnosis and post-treatment, and at least one post-treatment assessment of PUCAI/PCDAI, calprotectin, or endoscopy. The study employed Spearman and Pearson correlation tests to analyze the associations between vitamin D levels and IBD markers. Ethnicity and race were analyzed using t-tests and chi-square tests. Results No statistically significant correlations were found between changes in serum vitamin D levels and IBD markers (endoscopy results, calprotectin levels, PUCAI/PCDAI scores) for both UC and CD. Analysis of racial and ethnic disparities revealed that Hispanic patients had significantly higher post-treatment calprotectin levels compared to non-Hispanics, although other markers showed no significant differences. Vitamin D levels did not significantly differ between racial or ethnic groups. Conclusions This study found no significant correlation between serum vitamin D levels and IBD activity markers in pediatric patients. Despite initial hypotheses, vitamin D levels do not appear to be useful in assessing IBD remission or disease state. Racial and ethnic disparities in IBD severity were observed, but further research with larger sample sizes and more consistent data collection is needed to draw more definitive conclusions.