RESUMEN
Regulator of G-protein signalling (RGS) 10 plays critical roles in several immune related diseases. However, whether RGS10 is involved in colonic inflammation of ulcerative colitis (UC) is still obscure. This study aimed to investigate the role of RGS10 in UC. In this study, RGS10 expression was examined by quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, immunohistochemistry, and immunofluorescent analysis. Single-cell RNA sequencing of intestinal mucosa was performed to identify key immune cells with differentially expressed RGS10. RGS10 knockout mice were generated and established dextran sulphate sodium (DSS)-induced colitis. Expression of inflammatory cytokines on mRNA and protein levels was detected by qRT-PCR, enzyme-linked immunosorbent assay, and flow cytometry. We found that RGS10 expression was significantly elevated in UC patients, especially in CD4+ T cells, compared with healthy subjects. Intriguingly, RGS10 deficiency markedly alleviated DSS-induced colitis and decreased the proportion of Th1 and Th17 cells in lamina propria mononuclear cells (LPMCs), peripheral blood (PB), spleens, and mesenteric lymph nodes (mLNs). Mechanistically, RGS10 deficiency blocked the differentiation of Th1 and Th17 cells by inhibiting the phosphorylation of signal transducer and activator of transcription (STAT) 1 and STAT3. The co-immunoprecipitation analysis further showed that RGS10 could interact with protein tyrosine phosphatase non-receptor type 2 (PTPN2), and further regulated Th1 and Th17 cells differentiation of CD4+ T cells. In conclusion, RGS10 deficiency alleviated intestinal mucosal inflammation through inhibition of Th1/Th17 cell-mediated immune responses via interaction with PTPN2 in CD4+ T cells. Therefore, targeting RGS10 may represent a novel therapeutic approach for UC treatment.
RESUMEN
Inflammatory bowel disease (IBD) poses a significant challenge in modern medicine, with conventional treatments limited by efficacy and associated side effects, necessitating innovative therapeutic approaches. Mesenchymal stem cells (MSC) have emerged as promising candidates for IBD treatment due to their immunomodulatory properties and regenerative potential. This thesis aims to explore and compare various sources of MSC and evaluate their efficacy in treating IBD. This study comprehensively analyses MSC derived from multiple sources, including bone marrow, adipose tissue, umbilical cord, and other potential reservoirs. Core elements of this investigation include assessing differences in cell acquisition, immunomodulatory effects, and differentiation capabilities among these MSC sources, as well as comparing their clinical trial outcomes in IBD patients to their therapeutic efficacy in animal models. Through meticulous evaluation and comparative analysis, this thesis aims to elucidate disparities in the efficacy of different MSC sources for IBD treatment, thereby identifying the most promising therapeutic applications. The findings of this study are intended to advance our understanding of MSC biology and offer valuable insights for selecting the most effective MSC sources for personalized IBD therapy. Ultimately, this research endeavor will optimise therapeutic strategies for managing inflammatory bowel disease through the utilization of MSC.
Asunto(s)
Enfermedades Inflamatorias del Intestino , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Humanos , Enfermedades Inflamatorias del Intestino/terapia , Trasplante de Células Madre Mesenquimatosas/métodos , Animales , Diferenciación Celular/fisiología , Tejido Adiposo/citologíaRESUMEN
RATIONALE: Sarcomatoid hepatocellular carcinoma (SHC) is an uncommon variant of hepatocellular carcinoma (HCC), characterized by HCC features combined with sarcomatoid histology and manifestations. The simultaneous occurrence of HCC and hepatosarcomatoid carcinoma is infrequent. This report presents a distinctive instance of HCC coexisting with hepatic sarcomatoid carcinoma in a 56-year-old male. The case exhibits an unusual clinical presentation, diagnosis, treatment, and prognosis. Through the presentation of this case, we aspire to contribute novel concepts to shape forthcoming strategies encompassing SHC diagnosis and treatment. PATIENT CONCERNS: The 56-year-old male patient was admitted to the hospital, due to discovering a hepatic mass lasting for over 2 months. DIAGNOSES: Ultimately, combined hepatocellular and SHC diagnosis was conclusively confirmed through histopathological and imaging examinations. INTERVENTION: In this case, our approach encompassed hepatectomy coupled with ultrasound-guided radiofrequency ablation for HCC. Intraoperative ultrasound localization was employed for accurate tumor identification, followed by postoperative hepatic artery embolization to facilitate meticulous tumor resection. OUTCOMES: He underwent hepatic arteriography chemoembolization treatment and is currently stable, experiencing regular chemotherapy follow-up visits. LESSONS: The presence of distinct tumor types concurrently can influence treatment choices and prognosis. Given the intricate nature of this condition, crafting an optimal treatment strategy necessitates the incorporation of variables such as the patient age, tumor characteristics, liver function, and other pertinent factors.
Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Masculino , Humanos , Persona de Mediana Edad , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/terapia , Hepatectomía/métodos , PronósticoRESUMEN
RATIONALE: Inflammatory bowel disease (IBD), including Crohn disease (CD) and ulcerative colitis (UC), is a chronic immune-mediated disorder characterized by inflammation of the gastrointestinal tract. Patients with IBD are susceptible to various complications, including the coexistence of Clostridioides difficile infection (CDI). The incidence of IBD combined with difficile infection is higher in patients with compromised immune function, which can lead to increased mortality. PATIENT CONCERNS: A 43-year-old male presented with recurrent episodes of mucus and bloody stools persisting for more than a month without any identifiable triggering factors. Initially, the stool consistency was normal, but it progressively shifted to a loose and watery texture, with up to 8 occurrences daily. DIAGNOSES: This case underscores the diagnosis of severe UC through colonoscopy and colonic biopsy, along with the supplementary identification of a positive result for Clostridioides difficile in the fecal sample. INTERVENTIONS: The patient initiated infliximab therapy alongside a full vancomycin course, demonstrating the potential effectiveness of this intervention in managing early-stage ulcerative colitis with concurrent Clostridioides difficile infection. OUTCOMES: Following the completion of a full vancomycin course, the patient initiated infliximab therapy. The patient was free from significant discomfort, exhibited no fever, and had no mucopurulent bloody stools. A follow-up blood test indicated reduced inflammatory markers compared to the preoperative period, and the stools were normal. LESSONS: We illustrate the potential effectiveness of this medication by presenting an in-depth case report of a patient with early-stage UC. The report outlines the patient inclusion of infliximab to better manage UC inflammation alongside an adjunct vancomycin regimen, given the ineffectiveness of mesalazine therapy and the concurrent presence of Clostridium difficile infection. This case prompts consideration of therapeutic approaches for complex UC and contributes to advancing both research and clinical practice. Nonetheless, we should remain attentive to the variations and potential risks unique to each patient in order to formulate personalized treatment strategies.
Asunto(s)
Clostridioides difficile , Infecciones por Clostridium , Colitis Ulcerosa , Enfermedades Inflamatorias del Intestino , Masculino , Humanos , Adulto , Colitis Ulcerosa/tratamiento farmacológico , Vancomicina/uso terapéutico , Infliximab/uso terapéutico , Antibacterianos/uso terapéutico , Enfermedades Inflamatorias del Intestino/complicaciones , Infecciones por Clostridium/complicaciones , Infecciones por Clostridium/diagnóstico , Infecciones por Clostridium/tratamiento farmacológico , Inflamación/tratamiento farmacológicoRESUMEN
BACKGROUND: Schwannomas are uncommon tumors originating from Schwann cells, forming the neural sheath. They account for approximately 2%-6% of all mesenchymal tumors and are most commonly identified in peripheral nerve trunks, with rarity in the gastrointestinal tract. Among gastrointestinal locations, the stomach harbors the majority of nerve sheath tumors, while such occurrences in the sigmoid colon are exceptionally infrequent. CASE SUMMARY: This study presented a clinical case involving a 60-year-old female patient who, during colonoscopy, was diagnosed with a submucosal lesion that was later identified as a nerve sheath tumor. The patient underwent surgical resection, and the diagnosis was confirmed through immunohistochemistry. This study highlighted an exceptionally uncommon occurrence of a nerve sheath tumor in the sigmoid colon, which was effectively managed within our department. Additionally, a comprehensive review of relevant studies was conducted. CONCLUSION: The preoperative diagnosis of nerve sheath tumors poses challenges, as the definitive diagnosis still relies on pathology and immunohistochemistry. Although categorized as benign, these tumors have the potential to demonstrate malignant behavior. Consequently, the optimal treatment approach entails the complete surgical excision of the tumor, ensuring the absence of residual lesions at the margins.