RESUMO
RATIONALE: The interstitial pneumonia (IP) linked to vedolizumab (VDZ) in patients with ulcerative colitis (UC) is rare. Prompt diagnosis and treatment can improve patient outcomes. PATIENT CONCERNS: A 39-year-old man with UC who received VDZ as sole therapy developed symptoms such as chest tightness, cough, and suffocation. DIAGNOSES: IP was confirmed through pulmonary function tests, chest computed tomography, and bronchoscopic biopsy. INTERVENTIONS: The patient was given methylprednisolone and VDZ cessation. OUTCOMES: The patient's symptoms improved and remained symptom-free after nearly 2 years. LESSONS: VDZ-induced IP should be considered when evaluating pulmonary infections in UC patients treated with VDZ.
Assuntos
Anticorpos Monoclonais Humanizados , Colite Ulcerativa , Fármacos Gastrointestinais , Doenças Pulmonares Intersticiais , Humanos , Colite Ulcerativa/tratamento farmacológico , Masculino , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Doenças Pulmonares Intersticiais/induzido quimicamente , Doenças Pulmonares Intersticiais/tratamento farmacológico , Fármacos Gastrointestinais/efeitos adversos , Fármacos Gastrointestinais/uso terapêutico , Metilprednisolona/uso terapêuticoRESUMO
Background and aim: Insulin-like growth factor-1 may be involved in the epithelial-to-mesenchymal transition process. It can mitigate adverse effects when interacting with insulin-like growth factor binding protein 3. This study aimed to explore alterations in the expression of these two factors in the colonic tissue of mice with ulcerative colitis. Method: This study utilized animal models. Mice were randomly allocated into three distinct groups. Disease activity index assessment was performed first, followed by histological grading of colitis. Protein and mRNA expression levels were determined using Western blotting and RT-qPCR. Immunohistochemical detection was used to determine histochemistry scores. Pearson correlation and SPSS 25.0 software were used for data analysis. Results: The findings indicated a reduction in the expression of the two investigated factors as well as in epithelial-to-mesenchymal transition epithelial markers during inflammation, while the expression of noninflammatory factors increased. These effects were notably amplified following treatment. Interestingly, the changes in epithelial-to-mesenchymal transition-inducing factors and mesenchymal markers contradicted this trend. Pearson correlation analysis revealed a correlation between molecular indicators of change and epithelial-to-mesenchymal transition. Conclusion: Insulin-like growth factor-1 and insulin-like growth factor binding protein 3 may play a protective role in the development and progression of ulcerative colitis, potentially through their inhibition of the epithelial-to-mesenchymal transition. These factors hold promise as targets for the clinical diagnosis and treatment of ulcerative colitis.
RESUMO
Exosomes are a type of cell-derived vesicles that range in size from 30 to 100 nm. They are widely present in various organisms and participate in diverse biological processes, playing crucial roles in tumorigenesis and progression. This study aimed to investigate whether LINC01480 in tumor-derived exosomes is involved in the molecular mechanism of gastric cancer by competitively upregulating the VCAM1 expression through binding miR-204-5p. The study analyzed transcriptome data related to gastric cancer from the cancer genome atlas database and constructed a risk-scoring model for epithelial-mesenchymal transition (EMT)-related lncRNAs to identify eight EMT-related lncRNAs associated with prognosis. EMT-related mRNAs positively correlated with LINC01480 were screened in the ExoRBase database. In vitro cell experiments showed that exosomal LINC01480 can promote the proliferation, migration, invasion, and EMT of gastric cancer cells by upregulating VCAM1 expression through competitive binding with miR-204-5p. In vivo experiments on nude mice showed that exosomal LINC01480 promotes the development of gastric cancer. These results suggest that exosomal LINC01480 could be a potential therapeutic target for gastric cancer.
Assuntos
MicroRNAs , RNA Longo não Codificante , Neoplasias Gástricas , Animais , Camundongos , MicroRNAs/genética , Neoplasias Gástricas/genética , RNA Endógeno Competitivo , Camundongos Nus , RNA Longo não Codificante/genética , Proliferação de Células/genética , Linhagem Celular TumoralRESUMO
Pancreatic cancer remains one of the most lethal diseases worldwide owing to its late diagnosis, early metastasis, and poor prognosis. Because current therapeutic options are limited, there is an urgent need to investigate novel targeted treatment strategies. Pancreatic cancer faces significant metabolic challenges, principally hypoxia and nutrient deprivation, due to specific microenvironmental constraints, including an extensive desmoplastic stromal reaction. Pancreatic cancer cells have been shown to rewire their metabolism and energy production networks to support rapid survival and proliferation. Increased glucose uptake and glycolytic pathway activity during this process have been extensively described. However, growing evidence suggests that pancreatic cancer cells are glutamine addicted. As a nitrogen source, glutamine directly (or indirectly via glutamate conversion) contributes to many anabolic processes in pancreatic cancer, including amino acids, nucleobases, and hexosamine biosynthesis. It also plays an important role in redox homeostasis, and when converted to α-ketoglutarate, glutamine serves as an energy and anaplerotic carbon source, replenishing the tricarboxylic acid cycle intermediates. The present study aims to provide a comprehensive overview of glutamine metabolic reprogramming in pancreatic cancer, focusing on potential therapeutic approaches targeting glutamine metabolism in pancreatic cancer.
RESUMO
To select an optimal treatment, it is crucial to evaluate the risk of lymph node metastasis (LNM) in patients with superficial esophageal squamous cell carcinoma (SESCC). The research aimed to explore more risk factors than before and construct a practical nomogram to predict LNM in patients with SESCC. We retrospectively reviewed 1080 patients diagnosed with esophageal cancer who underwent esophagectomy with lymphadenectomy between January 2013 and October 2021 at the Affiliated Hospital of Qingdao University. The clinical parameters, endoscopic features, and pathological characteristics of the 123 patients that were finally enrolled in this study were collected. The independent risk factors for LNM were determined using univariate and multivariate analyses. Using these factors, a nomogram was constructed to predict LNM. LNM was observed in 21 patients. Univariate analysis showed that the absence or presence of hypertriglyceridemia, tumor location, lesion size, macroscopic type, invasion depth, differentiation, absence or presence of lymphovascular invasion (LVI), and perineural invasion were significantly associated with LNM. According to the multivariate analysis, hypertriglyceridemia, tumors located in the lower thoracic esophagus, lesion size > 20 mm, submucosal invasion, and LVI were independent risk factors for LNM. A nomogram was established using these 5 factors. It showed good calibration and discrimination. Hypertriglyceridemia, tumors located in the lower thoracic esophagus, lesion size > 20 mm, submucosal invasion, and LVI were independent risk factors for LNM. A nomogram was constructed using these 5 factors. This model can help clinicians assess the risk of LNM in patients with SESCC for optimal treatment selection.
Assuntos
Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Hiperlipidemias , Hipertrigliceridemia , Humanos , Carcinoma de Células Escamosas do Esôfago/cirurgia , Carcinoma de Células Escamosas do Esôfago/patologia , Neoplasias Esofágicas/cirurgia , Neoplasias Esofágicas/patologia , Nomogramas , Metástase Linfática/patologia , Estudos Retrospectivos , Carcinoma de Células Escamosas/patologia , Excisão de Linfonodo , Fatores de Risco , Invasividade Neoplásica/patologia , Linfonodos/cirurgia , Linfonodos/patologiaRESUMO
Background: The gut microbiota is closely linked to cholesterol metabolism-related diseases such as obesity and cardiovascular diseases. However, whether gut microbiota plays a causal role in cholelithiasis remains unclear. Aims: This study explored the causal relationship between gut microbiota and cholelithiasis. We hypothesize that the gut microbiota influences cholelithiasis development. Methods: A two-sample Mendelian randomization method was combined with STRING analysis to test this hypothesis. Summary data on gut microbiota and cholelithiasis were obtained from the MiBioGen (n=13,266) and FinnGen R8 consortia (n=334,367), respectively. Results: Clostridium senegalense, Coprococcus3, and Lentisphaerae increased the risk of cholelithiasis and expressed more bile salt hydrolases. In contrast, Holdemania, Lachnospiraceae UCG010, and Ruminococcaceae NK4A214 weakly expressed bile salt hydrolases and were implied to have a protective effect against cholelithiasis by Mendelian randomization analysis. Conclusion: Gut microbiota causally influences cholelithiasis and may be related to bile salt hydrolases. This work improves our understanding of cholelithiasis causality to facilitate the development of treatment strategies.
Assuntos
Doenças Cardiovasculares , Microbioma Gastrointestinal , Humanos , Microbioma Gastrointestinal/genética , Análise da Randomização Mendeliana , Clostridiales , Ácidos e Sais Biliares , Estudo de Associação Genômica AmplaRESUMO
Background: Lymph node status is an important prognostic indicator and it significantly influences treatment decisions for colorectal cancer (CRC). The objective of this study was to evaluate the ability of serum monosaccharides in predicting lymph node metastasis (LNM) and prognosis. Methods: High performance anion exchange chromatography coupled with pulsed amperometric detector (HPAEC-PAD) was used to quantify serum monosaccharides from 252 CRC patients. Receiver operating characteristic (ROC) curves were used to evaluate predictive performance of parameters. Predictors of LNM were evaluated by univariate and multivariate analyses. The prognostic role of the factors was evaluated by survival analysis. Results: The levels of serum mannose (Man) and galactose (Gal) were significantly increased in patients with LNM (p <0.0001, p =0.0017, respectively). The area under the curves (AUCs) of Man was 0.8140, which was higher than carcinoembryonic antigen (CEA) (AUC =0.6523). Univariate and multivariate analyses demonstrated histologic grade (G3) (odds ratio [OR] =2.60, p =0.043), histologic grade (mucin-producing subtype) (odds ratio [OR] =3.38, p =0.032), lymphovascular invasion (LVI) (OR =2.42, p <0.01), CEA (>5ng/ml) (OR =1.85, p =0.042) and high Man (OR =2.65, p =0.006) to be independent risk factors of LNM. The survival analysis showed that the high serum Man was independent risk factor for poor prognosis in CRC patients (HR=1.75, p =0.004). Conclusions: The Man is superior to CEA in prediction of LNM for CRC patients. Man is expected to be a predictor for LNM in CRC. High serum Man is associated with poor prognosis of CRC patients.
RESUMO
Colorectal cancer (CRC) is identified as a primary cause of death around the world. The current chemotherapies are not cost-effective. Therefore, finding novel potential therapeutic target is urgent. Titin (TTN) is a muscle protein that is critical in hypertrophic cardiomyopathy. However, its role in CRC is not well understood. The study focused on exploring the possible role of TTN in CRC carcinogenesis. TTN mRNA and protein expression levels presented an obvious downregulation in CRC tissue samples, relative to normal control (p < 0.05). TTN expression significantly correlated with the clinical stage (normal vs. Stage 1, p < 0.05; normal vs. Stage 4, p < 0.05), node metastasis (normal vs. N1, p < 0.05; N1 vs. N2, p < 0.05), histological type (normal vs. adenocarcinoma, p < 0.05), race (Caucasian vs. Asian, p < 0.05; African-American vs. Asian, p < 0.05) and TP53 mutation (normal vs. TP53 mutation, p < 0.05), considering The Cancer Genome Atlas database. However, for patients who had higher TTN expression, the overall survival was remarkably shorter than patients who had low TTN expression. Furthermore, TTN was lowly expressed in four CRC cell lines. TTN overexpression facilitated CRC cells in terms of the proliferation, metastasis and invasion. Based on gene set enrichment analysis, the ERB pathway might be responsible for TTN-related CRC. Besides, TTN was involved in the response to azacitidine. Overall, TTN might serve as a potential novel therapeutic target for treating and overcoming chemotherapy resistance in CRC.
Assuntos
Neoplasias Colorretais , MicroRNAs , Humanos , Conectina/genética , Conectina/metabolismo , MicroRNAs/genética , Proteínas Musculares/genética , Mutação/genética , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismoRESUMO
BACKGROUND: Dysbiosis of the gut microbiota is closely linked to hyperuricemia. However, the effect of the microbiome on uric acid (UA) metabolism remains unclear. This study aimed to explore the mechanisms through which microbiomes affect UA metabolism with the hypothesis that modifying the intestinal microbiota influences the development of hyperuricemia. RESULTS: We proposed combining an antibiotic strategy with protein-protein interaction analysis to test this hypothesis. The data demonstrated that antibiotics altered the composition of gut microbiota as UA increased, and that the spectrum of the antibiotic was connected to the purine salvage pathway. The antibiotic-elevated UA concentration was dependent on the increase in microbiomes that code for the proteins involved in purine metabolism, and was paralleled by the depletion of bacteria-coding enzymes required for the purine salvage pathway. On the contrary, the microbiota with abundant purine salvage proteins decreased hyperuricemia. We also found that the antibiotic-increased microbiota coincided with a higher relative abundance of bacteria in hyperuricemia mice. CONCLUSIONS: An antibiotic strategy combined with the prediction of microbiome bacterial function presents a feasible method for defining the key bacteria involved in hyperuricemia. Our investigations discovered that the core microbiomes of hyperuricemia may be related to the gut microbiota that enriches purine metabolism related-proteins. However, the bacteria that enrich the purine salvage-proteins may be a probiotic for decreasing urate, and are more likely to be killed by antibiotics. Therefore, the purine salvage pathway may be a potential target for the treatment of both hyperuricemia and antibiotic resistance.
Assuntos
Microbioma Gastrointestinal , Hiperuricemia , Camundongos , Animais , Antibacterianos/efeitos adversos , Disbiose/microbiologia , Bactérias/genética , Purinas/efeitos adversosRESUMO
BACKGROUND: Ulcerative colitis (UC) is considered an immune-mediated disease. The disorder of T-lymphocyte subsets plays an important role in the pathogenesis of UC. The aim of this study was to evaluate the significance of peripheral blood T-lymphocyte subsets in assessing disease severity and predicting clinical outcomes in UC patients. METHODS: The retrospective case-control study was performed in 116 UC patients with active disease and 90 healthy controls (HC). The UC patients included were followed up for 180 days. Analyses of t-test, Spearman's correlation coefficient, multivariable Cox regression analysis, receiver operating characteristic (ROC) curves and cumulative survival analysis were done. RESULTS: The UC patients had lower proportions of CD4+T cells (42.85%±9.77% vs 45.71%±7.94%, P=0.021) and higher proportion of CD8+T cells (27.88%±8.86% vs 25.00%±6.47%, P=0.008) than HC. The severely active UC patients had higher proportion of CD3+HLA-DR+ T cells (8.83%±6.55% vs 2.80%±1.55%, P<0.001; 8.83%±6.55% vs 4.06%±5.01%, P<0.001) and CD8+T cells (31.35%±8.49% vs 26.98%±7.98%, P=0.029; 31.35%±8.49% vs 25.46%±9.15%, P=0.003) than mild and moderate group, whereas lower proportion of CD4+CD25+T cells (2.86%±1.35% vs 3.46%±1.07%, P=0.034) than mild group and CD4+T cells (40.40%±9.36% vs 44.73%±10.39%, P=0.049) than moderate group. The area under the curve (AUC) of CD3+HLA-DR+ T cells for assessing severely active UC was 0.885, with the cut-off value of 5.33%. The sensitivity was 76.32% and specificity was 89.74%. The combination of CD3+HLA-DR+ T cells and CRP had stronger assessment value with AUC of 0.929. The AUC of CD8+T cells, CD4+/CD8+ ratio and CD4+CD25+T cells for assessing disease severity was 0.677, 0.669 and 0.631 respectively. Within the 180 days follow-up, 24 patients (20.69%) had UC-related readmission or surgery, with higher proportion of CD3+HLA-DR+ T cells (10.66%±9.52% vs 3.88%±2.56%, P=0.003) and CD8+T cells (31.19%±10.59% vs 27.01%±8.20%, P=0.039) than those without readmission and surgery. The proportion of CD3+HLA-DR+ T cells was the independent predictor of UC-related readmission or surgery (HR=1.109, P=0.002). The AUC of CD3+HLA-DR+ T cells for predicting readmission or surgery was 0.796 with the cut-off value of 5.38%. UC patients with CD3+HLA-DR+T cells proportion>5.38% had a shorter time to readmission or surgery (log-rank test, P<0.001). CONCLUSIONS: The combination of CD3+HLA-DR+T cells and CRP may be potential biomarker of disease severity in UC patients. The high proportion of CD3+HLA-DR+T cells may be associated with an increased risk of readmission or surgery in UC patients.
Assuntos
Colite Ulcerativa , Humanos , Estudos Retrospectivos , Estudos de Casos e Controles , Subpopulações de Linfócitos T , Biomarcadores , Antígenos HLA-DR , Gravidade do PacienteRESUMO
Background and aims: Compared with self-prepared LRD, a prepackaged low-residue diet (LRD) can improve patient compliance, but whether it can further improve the quality of bowel preparation is uncertain. The study aimed to compare the application of the prepackaged formula LRD with self-prepared LRD in bowel preparation for colonoscopy. Methods: A multicenter randomized controlled trial was conducted in 15 centers. The eligible subjects were randomly assigned to one of two groups: the formula LRD group and the self-prepared LRD group. On the day before the colonoscopy, subjects in the self-prepared LRD group were instructed to consume a restricted LRD prepared by themselves, while subjects in the formula LRD group were given six bags of prepackaged formula LRD and instructed to consume them according to their individual need. The primary outcome was an adequate bowel preparation rate. Secondary outcomes mainly included Boston Bowel Preparation Scale (BBPS) scores, dietary restriction compliance rate, tolerance, satisfaction, adenoma detection rate (ADR), and adverse reactions. The trial was registered at ClinicalTrials.gov under the identifier NCT03943758. Results: A total of 550 subjects were recruited. Compared with the self-prepared LRD group, the formula LRD group showed a higher adequate bowel preparation rate (94.5 vs. 80.4%; P < 0.01), BBPS scores (7.87 ± 1.13 vs. 6.75 ± 1.47; P < 0.01), dietary compliance rate (92.4 vs. 78.9%; P < 0.01), tolerance (P < 0.01 in degree of hunger, intensity of physical strength, and negative influence on daily activities), satisfaction (8.56 ± 1.61 vs. 7.20 ± 2.02; P < 0.01), and ADR (25.6 vs. 16.0%; P < 0.01). There was no significant difference in adverse reactions. Conclusion: Compared with self-prepared LRD, the formula LRD showed similar safety and higher bowel preparation quality, compliance, and tolerance in bowel preparation. More formula LRDs could be designed according to different dietary habits and ethnic populations, and further researches are warranted to confirm their effect. Clinical trial registration: https://register.clinicaltrials.gov, identifier: NCT03943758.
RESUMO
PURPOSE: The goal of this study was to examine the role of sodium butyrate in preserving the intestinal mucosal barrier and reducing hyperuricemia (HUA). METHODS: First, we established a mouse model of HUA via intraperitoneal injection of potassium oxonate together with a yeast-rich diet to detect the levels of serum uric acid (UA) and fecal short-chain fatty acids (SCFAs). Then, in vitro, different concentrations of UA and sodium butyrate (NaB) were used to treat LS174T and Caco2 cells. The effects of UA and NaB on the gut barrier were determined based on the expression levels of MUC2, ZO-1, and Occludin.Finally, C57BL/6 mice were used to model HUA, and these mice were administered 200 mg·kg-1·d-1 NaB by gavage to counter the HUA. The effect of NaB on HUA in the intestinal tract was elucidated by determining serum UA levels, inflammatory parameters, epithelial barrier integrity, and via histological analysis. RESULTS: The data showed that the content of fecal SCFAs in HUA mice decreased. Additionally, in LS174T and Caco2 cells, NaB reversed the decrease of ZO-1, Occludin, and MUC2 protein expression caused by high UA levels. Furthermore, NaB decreased serum UA of HUA mice, and reversed both the decreased expression of MUC2, ZO-1, Occludin, and ABCG2 proteins and the increased level of inflammatory factors in the intestinal tissues of these mice. CONCLUSION: The HUA mouse model showed intestinal barrier damage. NaB protected the intestinal barrier of HUA mice and reduced the serum UA level.
Assuntos
Hiperuricemia , Humanos , Camundongos , Animais , Ácido Butírico/farmacologia , Hiperuricemia/tratamento farmacológico , Hiperuricemia/metabolismo , Ácido Úrico/metabolismo , Ocludina/metabolismo , Células CACO-2 , Camundongos Endogâmicos C57BL , Ácidos Graxos Voláteis , Modelos Animais de DoençasRESUMO
RATIONALE: Gastric hamartomatous inverted polyps (GHIP) is not a common disease, and it has rarely been reported in the literature. Preoperative diagnosis is difficult due to the deep position and surface covered with normal gastric mucosa. However, with the progress of endoscopic technology, endoscopic submucosal dissection (ESD) can play a crucial role in the diagnosis and treatment of GHIP. PATIENT CONCERNS: A 61-year-old Chinese man underwent gastroscopy due to abdominal pain 2 months prior that revealed chronic superficial nonatrophic gastritis with erosion and a submucosal tumor in the gastric body (an ultrasound gastroscopy was recommended). Therefore, he was admitted to our hospital for further diagnosis and treatment. DIAGNOSES: A hemispherical submucosal tumor was found in the middle segment of the stomach, with a size of approximately 30 mm × 35 mm and a smooth surface without central ulceration or mucosal bridge formation. Ultrasound gastroscopy showed that the lesion was a hypoechoic mass with uniform internal echo originating from the muscularis propria. INTERVENTIONS: The tumor was completely removed by using ESD. The postoperative pathological results indicated a monocystic structure in the submucosa that was not connected with the surface mucosa. The surface of the cyst was covered with foveolar cells and mucous-neck cells (part of which had low-grade intraepithelial neoplasia), and GHIP was considered to be diagnosed. OUTCOMES: According to the abovementioned endoscopic and pathological features, the patient was finally diagnosed with GHIP. The patient was successfully discharged after surgery and received regular follow-up observations. LESSONS: GHIP is located in the submucosa layer and has the potential risk of malignant transformation. However, it is not easy to diagnose by using gastroscopy and ultrasound gastroscopy. ESD can obtain complete specimens, which contributes to the diagnosis and treatment of GHIP.
Assuntos
Pólipos Adenomatosos , Ressecção Endoscópica de Mucosa , Hamartoma , Neoplasias Gástricas , Masculino , Humanos , Pessoa de Meia-Idade , Resultado do Tratamento , Mucosa Gástrica/cirurgia , Mucosa Gástrica/patologia , Gastroscopia/métodos , Pólipos Adenomatosos/patologia , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Hamartoma/diagnóstico , Hamartoma/cirurgia , Hamartoma/patologiaRESUMO
BACKGROUND AND PURPOSE: Although endoscopic submucosal dissection (ESD) is considered standard treatment for early gastric cancer (EGC), patients with non-curative resection (NCR) of ESD may still require gastrectomy. The systemic immune-inflammation index (SII) showed great potential in predicting the prognosis of gastric cancer patients. This study aims to investigate the predictive validity of SII of NCR in EGC patients. METHODS: We reviewed data from EGC patients who underwent ESD in the past. The relationship between SII and clinicopathologic features was investigated. We used Receiver operating characteristic curves to compare the predictive values of NCR between SII and other inflammation indices. Binary logistic analysis was used to identify independent risk factors for NCR. These factors were then used to construct a predictive nomogram. RESULTS: SII was associated with larger tumor size, male gender, older age, submucosal invasion, and a greater risk of NCR. SII showed better predictivity of NCR than platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR). SII [odds ratio (OR) = 1.003, P = 0.001], NLR (OR = 1.520, P = 0.029), PLR (OR = 1.009, P = 0.010), upper stomach tumors (OR = 16.393, P < 0.001), poorly differentiated type (OR = 29.754, P < 0.001), ulceration (OR = 4.814, P = 0.001), and submucosal invasion (OR = 48.91, P < 0.001) were independent risk factors for NCR. The nomogram model based on these factors exhibited superior concordance and accuracy. CONCLUSION: SII could be considered a simple and effective predictor of NCR of ESD in EGC patients.
Assuntos
Ressecção Endoscópica de Mucosa , Neoplasias Gástricas , Humanos , Masculino , Mucosa Gástrica/patologia , Inflamação/patologia , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/patologia , FemininoRESUMO
BACKGROUND: Amino acid transporters play an important role in supplying nutrition to cells and are associated with cell proliferation. L-type amino acid transporter 1 (LAT1) is highly expressed in many types of cancers and promotes tumor growth; however, how LAT1 affects tumor development is not fully understood. METHODS: To investigate the role of LAT1 in intestinal tumorigenesis, mice carrying LAT1 floxed alleles that also expressed Cre recombinase from the promoter of gene encoding Villin were crossed to an ApcMin/+ background (LAT1fl/fl; vil-cre; ApcMin/+), which were subject to analysis; organoids derived from those mice were also analyzed. RESULTS: This study showed that LAT1 was constitutively expressed in normal crypt base cells, and its conditional deletion in the intestinal epithelium resulted in fewer Paneth cells. LAT1 deletion reduced tumor size and number in the small intestine of ApcMin/+ mice. Organoids derived from LAT1-deleted ApcMin/+ intestinal crypts displayed fewer spherical organoids with reduced Wnt/ß-catenin target gene expression, suggesting a low tumor-initiation capacity. Wnt3 expression was decreased in the absence of LAT1 in the intestinal epithelium, suggesting that loss of Paneth cells due to LAT1 deficiency reduced the risk of tumor initiation by decreasing Wnt3 production. CONCLUSIONS: LAT1 affects intestinal tumor development in a cell-extrinsic manner through reduced Wnt3 expression in Paneth cells. Our findings may partly explain how nutrient availability can affect the risk of tumor development in the intestines.
Assuntos
Proteína da Polipose Adenomatosa do Colo , Sistema y+L de Transporte de Aminoácidos , Neoplasias Intestinais , Celulas de Paneth , Animais , Camundongos , Transformação Celular Neoplásica/genética , Mucosa Intestinal/patologia , Neoplasias Intestinais/metabolismo , Intestino Delgado/patologia , Intestinos , Celulas de Paneth/metabolismo , Celulas de Paneth/patologia , Proteína da Polipose Adenomatosa do Colo/metabolismo , Sistema y+L de Transporte de Aminoácidos/metabolismoRESUMO
BACKGROUND: Patients with inflammatory bowel disease tend to have malnutrition, frailty, and low muscle mass, which impact on poor clinical outcomes. Abdominal computed tomography is frequently used to assess body composition. This study aimed to evaluate the association of low muscle mass and readmission within 1 year in patients with inflammatory bowel disease during hospitalization and follow-up. METHODS: A total of 211 patients with inflammatory bowel disease who had undergone computed tomography scans were included retrospectively. They were divided into subgroups based on disease activity. The male patients with skeletal muscle index ≤45.4 cm2/m2 and the female patients with skeletal muscle index ≤ 34.3 cm2/m2 were considered to have low muscle mass. Sociodemographic, clinical, and prognostic data were recorded. The analyses were done using the Statistical Package for the Social Sciences 25.0 software. RESULTS: The prevalence rate of low muscle mass was 64.7%. Low body mass index and hemoglobin, high erythrocyte sedimentation rate, smoking, and gastrointestinal surgery history were risk factors for low muscle mass (P < .05). Patients using steroids and biologics and using them more than 7 months were prone to develop low muscle mass and readmission (P < .05), while patients using immunomodulators were not. Inflammatory bowel disease patients with visceral fat area/subcutaneous fat area ≥0.71 were likely to readmit within 1 year than those with visceral fat area/subcutaneous fat area <0.71 (P < .05). Overweight or obese inflammatory bowel disease patients with low muscle mass had a shorter time to readmission than those without low muscle mass (P < .05). CONCLUSIONS: Overweight/obese inflammatory bowel disease patients with low muscle mass and patients using steroids and biologics have shorter time to readmission within 1 year regardless of disease activity.
Assuntos
Doenças Inflamatórias Intestinais , Sobrepeso , Humanos , Masculino , Feminino , Estudos Retrospectivos , Readmissão do Paciente , Músculo Esquelético , Composição Corporal , Obesidade , Índice de Massa Corporal , Gordura Intra-AbdominalRESUMO
FAT atypical cadherin 1 (FAT1) is a mutant gene frequently found in human cancers and mainly accumulates at the plasma membrane of cancer cells. Emerging evidence has implicated FAT1 in the progression of gastric cancer (GC). This study intended to identify a regulatory network related to FAT1 in GC development. Upregulated expression of FAT1 was confirmed in GC tissues, and silencing FAT1 was observed to result in suppression of GC cell oncogenic phenotypes. Mechanistic investigation results demonstrated that FAT1 upregulated AP-1 expression by phosphorylating c-JUN and c-FOS, whereas LINC00857 elevated the expression of FAT1 by recruiting a transcription factor TFAP2C. Functional experiments further suggested that LINC00857 enhanced the malignant biological characteristics of GC cells through TFAP2C-mediated promotion of FAT1. More importantly, LINC00857 silencing delayed the tumor growth and blocked epithelial-mesenchymal transition in tumor-bearing mice, which was associated with downregulated expression of TFAP2C/FAT1. To conclude, LINC00857 plays an oncogenic role in GC through regulating the TFAP2C/FAT1/AP-1 axis. Therefore, this study contributes to extended the understanding of gastric carcinogenesis and LINC00857 may serve as a therapeutic target for GC.
Assuntos
Neoplasias Gástricas , Humanos , Animais , Camundongos , Neoplasias Gástricas/genética , Fator de Transcrição AP-1/genética , Linhagem Celular Tumoral , Carcinogênese/patologia , Regulação Neoplásica da Expressão Gênica , Proliferação de Células/genética , Transição Epitelial-Mesenquimal/genética , Movimento Celular , Caderinas/genética , Caderinas/metabolismo , Fator de Transcrição AP-2/genéticaRESUMO
BACKGROUND: Endoscopic evaluation in diagnosing and managing ulcerative colitis (UC) is becoming increasingly important. Several endoscopic scoring systems have been established, including the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) score and Mayo Endoscopic Subscore (MES). Furthermore, the Toronto Inflammatory Bowel Disease Global Endoscopic Reporting (TIGER) score for UC has recently been proposed; however, its clinical value remains unclear. AIM: To investigate the clinical value of the TIGER score in UC by comparing it with the UCEIS score and MES. METHODS: This retrospective study included 166 patients with UC who underwent total colonoscopy between January 2017 and March 2023 at the Affiliated Hospital of Qingdao University (Qingdao, China). We retrospectively analysed endoscopic scores, laboratory and clinical data, treatment, and readmissions within 1 year. Spearman's rank correlation coefficient, receiver operating characteristic curve, and univariate and multivariable logistic regression analyses were performed using IBM SPSS Statistics for Windows, version 26.0 (IBM Corp., Armonk, NY, United States) and GraphPad Prism version 9.0.0 for Windows (GraphPad Software, Boston, Massachusetts, United States). RESULTS: The TIGER score significantly correlated with the UCEIS score and MES (r = 0.721, 0.626, both P < 0.001), showed good differentiating values for clinical severity among mild, moderate, and severe UC [8 (4-112.75) vs 210 (109-219) vs 328 (219-426), all P < 0.001], and exhibited predictive value in diagnosing patients with severe UC [area under the curve (AUC) = 0.897, P < 0.001]. Additionally, the TIGER (r = 0.639, 0,551, 0.488, 0.376, all P < 0.001) and UCEIS scores (r = 0.622, 0,540, 0.494, and 0.375, all P < 0.001) showed stronger correlations with laboratory and clinical parameters, including C-reactive protein, erythrocyte sedimentation rate, length of hospitalisation, and hospitalisation costs, than MES (r = 0.509, 0,351, 0.339, and 0.270, all P < 0.001). The TIGER score showed the best predictability for patients' recent advanced treatment, including systemic corticosteroids, biologics, or immunomodulators (AUC = 0.848, P < 0.001) and 1-year readmission (AUC = 0.700, P < 0.001) compared with the UCEIS score (AUC = 0.762, P < 0.001; 0.627, P < 0.05) and MES (AUC = 0.684, P < 0.001; 0.578, P = 0.132). Furthermore, a TIGER score of ≥ 317 was identified as an independent risk factor for advanced UC treatment (P = 0.011). CONCLUSION: The TIGER score may be superior to the UCIES score and MES in improving the accuracy of clinical disease severity assessment, guiding therapeutic decision-making, and predicting short-term prognosis.
Assuntos
Colite Ulcerativa , Doenças Inflamatórias Intestinais , Humanos , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/terapia , Estudos Retrospectivos , Colonoscopia , Adjuvantes ImunológicosRESUMO
RATIONALE: Intestinal stricture and obstruction are rare complications of ulcerative colitis (UC). Currently, there are only a few studies on the treatment of UC with intestinal stenosis, however there are no reports on the treatment of UC with benign intestinal stenosis with ustekinumab (UST). PATIENT CONCERNS: A 22-year-old woman was admitted to our hospital due to a 3-year history of recurrent bloody mucous in stool with intermittent abdominal pain and distension developed in the past month. She was steroid-dependent and had developed a secondary loss of response to infliximab. DIAGNOSES: She was diagnosed with UC combined with incomplete intestinal obstruction due to stenosis. The stricture had a mixed pattern with both inflammatory and fibrotic components, with the former covering a larger section of the intestine. INTERVENTIONS: The patient was given UST for 56 weeks. OUTCOMES: The patient's symptoms subsided after treatment with UST. The ulcers healed, and the stenosis was reduced. LESSONS: UST is effective against UC with benign intestinal stenosis. It is thought that UST inhibits the production of transforming growth factor-ß and interleukin-17, leading to the suppression of myofibroblast proliferation, ultimately alleviating intestinal stenosis.