Effects of vitamin family members on insulin resistance and diabetes complications.

The following letter to the editor highlights the article "Effects of vitamin D supplementation on glucose and lipid metabolism in patients with type 2 diabetes mellitus and risk factors for insulin resistance" in World J Diabetes 2023 Oct 15; 14 (10): 1514-1523. It is necessary to explore the role of vitamin family members in insulin resistance and diabetes complications.

Limonin inhibits the stemness of cancer stem-like cells derived from colorectal carcinoma cells potentially via blocking STAT3 signaling.

BACKGROUND: Limonin is one of the most abundant active ingredients of Tetradium ruticarpum. It exerts antitumor effects on several kinds of cancer cells. However, whether limonin exerts antitumor effects on colorectal cancer (CRC) cells and cancer stem-like cells (CSCs), a subpopulation responsible for a poor prognosis, is unclear. AIM: To evaluate the effects of limonin on CSCs derived from CRC cells. METHODS: CSCs were collected by culturing CRC cells in serum-free medium. The cytotoxicity of limonin against CSCs and parental cells (PCs) was determined by cholecystokinin octapeptide-8 assay. The effects of limonin on stemness were detected by measuring stemness hallmarks and sphere formation ability. RESULTS: As expected, limonin exerted inhibitory effects on CRC cell behaviors, including cell proliferation, migration, invasion, colony formation and tumor formation in soft agar. A relatively low concentration of limonin decreased the expression stemness hallmarks, including Nanog and ß-catenin, the proportion of aldehyde dehydrogenase 1-positive CSCs, and the sphere formation rate, indicating that limonin inhibits stemness without presenting cytotoxicity. Additionally, limonin treatment inhibited invasion and tumor formation in soft agar and in nude mice. Moreover, limonin treatment significantly inhibited the phosphorylation of STAT3 at Y705 but not S727 and did not affect total STAT3 expression. Inhibition of Nanog and ß-catenin expression and sphere formation by limonin was obviously reversed by pretreatment with 2 µmol/L colievlin. CONCLUSION: Taken together, these results indicate that limonin is a promising compound that targets CSCs and could be used to combat CRC recurrence and metastasis.

Machine learning-based B cell-related diagnostic biomarker signature and molecular subtypes characteristic of ulcerative colitis.

As an inflammatory bowel disease, ulcerative colitis (UC) does not respond well to current treatments. It is of positive clinical significance to further study the pathogenesis of UC and find new therapeutic targets. B lymphocytes play an important role in the pathogenesis of UC. The effect of anti-CD20 therapy on UC also provides new evidence for the involvement of B cells in UC process additionally, suggesting the important role and potential therapeutic value of B cells in UC. In this study, we screened the most critical immune cell-related gene modules associated with UC and found that activated B cells were closely related to the gene modules. Subsequently, key activated B cell-associated gene (BRG) signatures were obtained based on WGCNA and differential expression analysis, and three overlapping BRG-associated genes were obtained by RF and LASSO algorithms as BRG-related diagnostic biomarkers for UC. Nomogram model was further performed to evaluate the diagnostic ability of BRG-related diagnostic biomarkers, subsequently followed by UC molecular subsets identification and immunoinfiltration analysis. We also further verified the expressions of the three screened BRGs in vitro by using an LPS-induced NCM460 cell line model. Our results provide new evidence and potential intervention targets for the role of B cells in UC from a new perspective.

PDHA1 Alleviates Myocardial Ischemia-Reperfusion Injury by Improving Myocardial Insulin Resistance During Cardiopulmonary Bypass Surgery in Rats.

OBJECTIVE: Cardiopulmonary bypass (CPB) is a requisite technique for thoracotomy in advanced cardiovascular surgery. However, the consequent myocardial ischemia-reperfusion injury (MIRI) is the primary culprit behind cardiac dysfunction and fatal consequences post-operation. Prior research has posited that myocardial insulin resistance (IR) plays a vital role in exacerbating the progression of MIRI. Nonetheless, the exact mechanisms underlying this phenomenon remain obscure. METHODS: We constructed pyruvate dehydrogenase E1 α subunit (PDHA1) interference and overexpression rats and used ascending aorta occlusion in an in vivo model of CPB-MIRI. We devised an in vivo model of CPB-MIRI by constructing rat models with both pyruvate dehydrogenase E1α subunit (PDHA1) interference and overexpression through ascending aorta occlusion. We analyzed myocardial glucose metabolism and the degree of myocardial injury using functional monitoring, biochemical assays, and histological analysis. RESULTS: We discovered a clear downregulation of glucose transporter 4 (GLUT4) protein content expression in the CPB I/R model. In particular, cardiac-specific PDHA1 interference resulted in exacerbated cardiac dysfunction, significantly increased myocardial infarction area, more pronounced myocardial edema, and markedly increased cardiomyocyte apoptosis. Notably, the opposite effect was observed with PDHA1 overexpression, leading to a mitigated cardiac dysfunction and decreased incidence of myocardial infarction post-global ischemia. Mechanistically, PDHA1 plays a crucial role in regulating the protein content expression of GLUT4 on cardiomyocytes, thereby controlling the uptake and utilization of myocardial glucose, influencing the development of myocardial insulin resistance, and ultimately modulating MIRI. CONCLUSION: Overall, our study sheds new light on the pivotal role of PDHA1 in glucose metabolism and the development of myocardial insulin resistance. Our findings hold promising therapeutic potential for addressing the deleterious effects of MIRI in patients.

Multifunctional roles of inflammation and its causative factors in primary liver cancer: A literature review.

Primary liver cancer is a severe and complex disease, leading to 800000 global deaths annually. Emerging evidence suggests that inflammation is one of the critical factors in the development of hepatocellular carcinoma (HCC). Patients with viral hepatitis, alcoholic hepatitis, and steatohepatitis symptoms are at higher risk of developing HCC. However, not all inflammatory factors have a pathogenic function in HCC development. The current study describes the process and mechanism of hepatitis development and its progression to HCC, particularly focusing on viral hepatitis, alcoholic hepatitis, and steatohepatitis. Furthermore, the roles of some essential inflammatory cytokines in HCC progression are described in addition to a summary of future research directions.

Acute or chronic inflammation role in gastrointestinal oncology.

The following letter to the editor highlights the review titled "Inflammatory bowel disease-related colorectal cancer: Past, present and future perspectives" in World J Gastrointest Oncol 2022 March 15; 14(3): 547-567. It is necessary to explore the role of inflammation in promoting tumorigenesis and development of gastrointestinal cancers.

Bioinformatics prediction of potential mechanisms and biomarkers underlying dilated cardiomyopathy.

BACKGROUND: Heart failure is a health burden responsible for high morbidity and mortality worldwide, and dilated cardiomyopathy (DCM) is one of the most common causes of heart failure. DCM is a disease of the heart muscle and is characterized by enlargement and dilation of at least one ventricle alongside impaired contractility with left ventricular ejection fraction < 40%. It is also associated with abnormalities in cytoskeletal proteins, mitochondrial ATP transporter, microvasculature, and fibrosis. However, the pathogenesis and potential biomarkers of DCM remain to be investigated. AIM: To investigate the candidate genes and pathways involved in DCM patients. METHODS: Two expression datasets (GSE3585 and GSE5406) were downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) between the DCM patients and healthy individuals were identified using the R package "linear models for microarray data." The pathways with common DEGs were analyzed via Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analyses. Moreover, a protein-protein interaction network (PPI) was constructed to identify the hub genes and modules. The MicroRNA Database was applied to predict the microRNAs (miRNAs) targeting the hub genes. Additionally, immune cell infiltration in DCM was analyzed using CIBERSORT. RESULTS: In total, 97 DEGs (47 upregulated and 50 downregulated) were identified. GO analysis showed that the DEGs were mainly enriched in "response to growth factor," "extracellular matrix," and "extracellular matrix structural constituent." KEGG pathway analysis indicated that the DEGs were mainly enriched in "protein digestion and absorption" and "interleukin 17 (IL-17) signaling pathway." The PPI network suggested that collagen type III alpha 1 chain (COL3A1) and COL1A2 contribute to the pathogenesis of DCM. Additionally, visualization of the interactions between miRNAs and the hub genes revealed that hsa-miR-5682 and hsa-miR-4500 interacted with both COL3A1 and COL1A2, and thus these miRNAs might play roles in DCM. Immune cell infiltration analysis revealed that DCM patients had more infiltrated plasma cells and fewer infiltrated B memory cells, T follicular helper cells, and resting dendritic cells. CONCLUSION: COL1A2 and COL3A1 and their targeting miRNAs, hsa-miR-5682 and hsa-miR-4500, may play critical roles in the pathogenesis of DCM, which are closely related to the IL-17 signaling pathway and acute inflammatory response. These results may provide useful clues for the diagnosis and treatment of DCM.

Combined therapy with early initiation of infliximab following drainage of perianal fistulising Crohn's disease: a retrospective cohort study.

BACKGROUND: Recent studies have confirmed that combined surgery and anti-TNF therapy could improve outcomes in patients with perianal fistulising Crohn's disease (PFCD). However, the optimal timing for infliximab infusion after surgical intervention is uncertain. We aimed to determine the long-term efficacy of early initiation of infliximab following surgery among PFCD patients. METHODS: We performed a retrospective cohort study of PFCD patients who received combined infliximab and surgical treatment between 2010 and 2018 at a tertiary referral hospital. Patients were grouped according to the time interval between surgery and infliximab infusion, with < 6 weeks into early infliximab induction group and > 6 weeks into delayed infliximab induction group. The primary outcome was to compare surgical re-intervention between early and delayed infliximab induction groups. The secondary outcomes were fistula healing and predictors associated with these outcomes of early infliximab induction approach. RESULTS: One hundred and seventeen patients were included (73 in early infliximab induction, 44 in delayed infliximab induction). The median interval between surgery and infliximab initiation was 9.0 (IQR 5.5-17.0) days in early infliximab induction group and 188.0 (IQR 102.25-455.75) days in delayed infliximab induction group. After followed-up for a median of 36 months, 61.6% of patients in early infliximab induction group and 65.9% in delayed infliximab induction group attained fistula healing (p = 0.643). The cumulative re-intervention rate was 23%, 32%, 34% in early infliximab induction group and 16%, 25%, 25% in delayed infliximab induction group, at 1, 2, and 3 years respectively (p = 0.235). Presence of abscess at baseline (HR = 5.283; 95% CI, 1.61-17.335; p = 0.006) and infliximab maintenance therapy > 3 infusions (HR = 3.691; 95% CI, 1.233-11.051; p = 0.02) were associated with re-intervention in early infliximab induction group. Presence of abscess at baseline also negatively influenced fistula healing (HR = 3.429, 95% CI, 1.216-9.668; p = 0.02). CONCLUSION: Although no clear benefit was shown compared with delayed infliximab induction group, early initiation of infliximab after surgery could achieve promising results for PFCD patients. Before infliximab infusion, durable drainage is required for patients with concomitant abscess or prolonged infliximab maintenance therapy.

Cardiac Fibroblast-Specific Knockout of PGC-1α Accelerates AngII-Induced Cardiac Remodeling.

Cardiac remodeling consisted of ventricular hypertrophy and interstitial fibrosis is the pathological process of many heart diseases. Fibroblasts as one of the major cells in the myocardium regulate the balance of the generation and degeneration of collagen, and these cells transform toward myofibroblasts in pathological state, contributing to the remodeling of the heart. Peroxisome proliferator-activated receptor-γ (PPAR-γ) coactivator-1α (PGC-1α) is vital to the function of mitochondria, which contributes to the energy production and reactive oxidative species (ROS)-scavenging activity in the heart. In this study, we found that fibroblast-specific PGC-1α KO induced cardiac remodeling especially fibrosis, and Angiotensin II (AngII) aggravated cardiac fibrosis, accompanied with a high level of oxidative stress response and inflammation.

The Role of Brown Adipose Tissue Dysfunction in the Development of Cardiovascular Disease.

Brown adipose tissue (BAT), consisted of brown adipocytes and stromal vascular fraction, which includes endothelial cells, lymphocytes, fibroblasts and stem cells, plays a vital role in regulating cardiovascular health and diseases. As a thermogenic organ, BAT can influence body through strengthening energy expenditure by promoting glucose and lipid metabolism. In addition, BAT is also an endocrine organ which is able to secret adipokines in an autocrine and/or paracrine fashion. BAT plays a protective role in cardiovascular system through attenuating cardiac remodeling and suppressing inflammatory response. In this review, we summarize the advances from the discovery of BAT to the present and provide an overview on the role of BAT dysfunction in cardiovascular diseases.

Association of hidradenitis suppurativa with Crohn's disease.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder characterized by recurrent nodules, abscesses, and sinus tracts. Crohn's disease (CD) is characterized by inflammation of the entire digestive tract and belongs to the group of inflammatory bowel diseases, and there are many extraintestinal manifestations, among which hidradenitis suppurativa is one of the rare extraintestinal manifestations. There appears to be a strong association between CD and HS based on clinical and histological similarities (sinus tract development, granulomatous inflammation, and scarring), intersections in pathogenesis (genetic loci, immune dysregulation mechanisms, and microbiome changes), and commonality in treatment. In this review, we summarize recent studies on the association between HS and CD.

T-cell senescence accelerates angiotensin II-induced target organ damage.

AIMS: Aging is a risk factor for cardiovascular diseases and adaptive immunity has been implicated in angiotensin (Ang) II-induced target organ dysfunction. Herein, we sought to determine the role of T-cell senescence in Ang II-induced target organ impairment and to explore the underlying mechanisms. METHODS AND RESULTS: Flow cytometric analysis revealed that T cell derived from aged mice exhibited immunosenescence. Adoptive transfer of aged T cells to immunodeficient RAG1 KO mice accelerates Ang II-induced cardiovascular and renal fibrosis compared with young T-cell transfer. Aged T cells also promote inflammatory factor expression and superoxide production in these target organs. In vivo and in vitro studies revealed that Ang II promotes interferon-gamma (IFN-γ) production in the aged T cells comparing to young T cells. Importantly, transfer of senescent T cell that IFN-γ KO mitigates the impairment. Aged T-cell-conditioned medium stimulates inflammatory factor expression and oxidative stress in Ang II-treated renal epithelial cells compared with young T cells, and these effects of aged T-cell-conditioned medium are blunted after IFN-γ-neutralizing antibody pre-treatment. CONCLUSION: These results provide a significant insight into the contribution of senescent T cells to Ang II-induced cardiovascular dysfunction and provide an attractive possibility that targeting T cell specifically might be a potential strategy to treat elderly hypertensive patients with end-organ dysfunction.

Molecular screening and clinicopathologic characteristics of Lynch-like syndrome in a Chinese colorectal cancer cohort.

Colorectal cancers (CRC) with microsatellite instability (MSI) or mismatch repair-deficiency (dMMR), but without detectable MMR germline mutations are termed Lynch-like syndrome (LLS). We assess the clinicopathologic and molecular characteristics of LLS tumors and the proportion in LLS, which remain poorly investigated in China. We enrolled 404 CRC patients with surgery in our institution from 2014 to 2018. LLS tumors were detected by a molecular stratification based on MMR protein expression, MLH1 methylation and MMR gene mutation. LLS tumors were profiled for germline mutations in 425 cancer-relevant genes. Among 42 MMR-deficient tumors, 7 (16.7%) were attributable to MLH1 methylation and 7 (16.7%) to germline mutations, leaving 28 LLS cases (66.6%). LLS tumors were diagnosed at a mean age of 60.7 years, had an almost equivalent ratio among rectum, left colon and right colon, and had high rates of lymph node metastases (50%, 4/28 N2). Most MMR gene mutations (88.2%, 15/17) in LLS tumors were variants of unknown significance (VUS). Two novel frameshift mutations were detected in ATM and ARID1A, which are emerging as candidate responsible genes for LLS. In this study, 28 (66.6%) MMRd tumors were classified as LLS, which were significantly higher than reports of western countries. LLS tumors were more likely to carry lymph node metastases. However, it's hard to differentiated LLS tumors from LS through family history, tumor location, histological type of tumors, immunohistochemistry (IHC) for MMR proteins and MSI analysis.

Optimized timing of using infliximab in perianal fistulizing Crohn's disease.

Infliximab (IFX), as a drug of first-line therapy, can alter the natural progression of Crohn's disease (CD), promote mucosal healing and reduce complications, hospitalizations, and the incidence of surgery. Perianal fistulas are responsible for the refractoriness of CD and represent a more aggressive disease. IFX has been demonstrated as the most effective drug for the treatment of perianal fistulizing CD. Unfortunately, a significant proportion of patients only partially respond to IFX, and optimization of the therapeutic strategy may increase clinical remission. There is a significant association between serum drug concentrations and the rates of fistula healing. Higher IFX levels during induction are associated with a complete fistula response in these patients. Given the apparent relapse of perianal fistulizing CD, maintenance therapy with IFX over a longer period seems to be more beneficial. It appears that patients without deep remission are at an increased risk of relapse after stopping anti-tumor necrosis factor agents. Thus, only patients in prolonged clinical remission should be considered for withdrawal of IFX treatment when biomarker and endoscopic remission is demonstrated, especially when the hyperintense signals of fistulas on T2-weighed images have disappeared on magnetic resonance imaging. Fundamentally, the optimal timing of IFX use is highly individualized and should be determined by a multidisciplinary team.

Non-SMC condensin I complex subunit D2 and non-SMC condensin II complex subunit D3 induces inflammation via the IKK/NF-κB pathway in ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) is a chronic, nonspecific intestinal inflammatory disease with undefined pathogenesis. Non-SMC condensin I complex subunit D2 (NCAPD2) and non-SMC condensin II complex subunit D3 (NCAPD3) play pivotal roles in chromosome assembly and segregation during both mitosis and meiosis. To date, there has been no relevant report about the functional role of NCAPD2 and NCAPD3 in UC. AIM: To determine the level of NCAPD2/3 in intestinal mucosa and explore the mechanisms of NCAPD2/3 in UC. METHODS: Levels of NCAPD2/3 in intestinal tissue were detected in 30 UC patients and 30 healthy individuals with in situ hybridization (ISH). In vitro, NCM60 cells were divided into the NC group, model group, si-NCAPD2 group, si-NCAPD3 group and si-NCAPD2+si-NCAPD3 group. Inflammatory cytokines were measured by ELISA, IKK and NF-κB were evaluated by western blot, and IKK nucleation and NF-κB volume were analyzed by immunofluorescence assay. RESULTS: Compared with expression in healthy individuals, NCAPD2 and NCAPD3 expression in intestinal tissue was significantly upregulated (P < 0.001) in UC patients. Compared with levels in the model group, IL-1ß, IL-6 and TNF-α in the si-NCAPD2, si-NCAPD3 and si-NCAPD2+si-NCAPD3 groups were significantly downregulated (P < 0.01). IKK and NF-κB protein expression in the si-NCAPD2, si-NCAPD3 and si-NCAPD2+si-NCAPD3 groups was significantly decreased (P < 0.01). Moreover, IKK nucleation and NF-κB volume were suppressed upon si-NCAPD2, si-NCAPD3 and si-NCAPD2+ si-NCAPD3 transfection. CONCLUSION: NCAPD2/3 is highly expressed in the intestinal mucosa of patients with active UC. Overexpression of NCAPD2/3 promotes the release of pro-inflammatory cytokines by modulating the IKK/NF-κB signaling pathway.

LINC01198 promotes proliferation and temozolomide resistance in a NEDD4-1-dependent manner, repressing PTEN expression in glioma.

BACKGROUND: Dysregulation of numerous lncRNAs has been recently confirmed in glioma; however, the majority of their roles and mechanisms involved in this notorious disease remain largely unclear. This study aims to explore the roles and molecular mechanisms of LINC01198 implicated in the proliferation and chemoresistance in glioma. RESULTS: LINC01198 was elevated in glioma, and this predicted a poorer prognosis for patients with glioma. LINC01198 knockdown inhibited, while LINC01198 overexpression promoted, glioma cell proliferation and resistance to temozolomide. Mechanistically, NEDD4-1 (neural precursor cell expressed, developmentally downregulated 4, E3 ubiquitin protein ligase) and phosphatase and tensin homolog (PTEN) were recruited by LINC01198, which functioned as a scaffold. Moreover, we showed that LINC01198 exerted its oncogenic activities by enhancing the NEDD4-1-dependent repression of PTEN. CONCLUSIONS: Our study elucidated the role of oncogenic LINC01198 in glioma proliferation and temozolomide resistance, and this role may serve as a promising target for glioma therapy. METHODS: LINC01198 expression in glioma tissues and that in paired normal tissues were measured by qRT-PCR. The functional roles of LINC01198 in glioma were demonstrated by a series of in vitro experiments. CCK-8 assay, RNA pulldown, RNA immunoprecipitation and western blotting were used to demonstrate the potential mechanisms of LINC01198.

ANALYSIS OF THE CLINICAL CHARACTERISTICS OF PERIANAL FISTULISING CROHN'S DISEASE IN A SINGLE CENTER.

BACKGROUND: Clinical characteristics are keys to improve identification and treatment of Crohn´s disease (CD) so that large sample analysis is of great value. AIM: To explore the clinical characteristics of perianal fistulising CD. METHODS: Analysis of 139 cases focused on their clinical data. RESULTS: The proportion of males and females is 3.3:1; the mean age is 28.2 years; 47.5% of patients had anal fistula before CD diagnosis. Patients with prior perianal surgery and medication accounted for 64.7% and 74.1% respectively. The L3 type of lesion was present in 49.6% and the B1 and B2 types for 51.8% and 48.2% respectively; complex anal fistula was diagnosed in 90.6%. Symptoms of diarrhea were found in 46% and perianal lesions alone in 29.5% of patients. Abnormal BMI values was present in 44.6%; active CD activity index in 64.7%; and 94.2% had active perianal disease activity index. A proportion of patients manifest abnormal C-reactive protein, erythrocyte sedimentation rate, platelet, hemoglobin and albumin. CONCLUSION: We suggest that patients with anal fistula associated to these clinical features should alert the medical team to the possibility of CD, which should be further investigated through endoscopy and imaging examination of alimentary tract to avoid the damage of anal function by routine anal fistula surgery.

Analysis of the clinical characteristics of perianal fistulising crohn's disease in a single center / Análise das características clínicas da doença de crohn fistulizante perianal em um único centro

ABSTRACT Background: Clinical characteristics are keys to improve identification and treatment of Crohn´s disease (CD) so that large sample analysis is of great value. Aim: To explore the clinical characteristics of perianal fistulising CD. Methods: Analysis of 139 cases focused on their clinical data. Results: The proportion of males and females is 3.3:1; the mean age is 28.2 years; 47.5% of patients had anal fistula before CD diagnosis. Patients with prior perianal surgery and medication accounted for 64.7% and 74.1% respectively. The L3 type of lesion was present in 49.6% and the B1 and B2 types for 51.8% and 48.2% respectively; complex anal fistula was diagnosed in 90.6%. Symptoms of diarrhea were found in 46% and perianal lesions alone in 29.5% of patients. Abnormal BMI values was present in 44.6%; active CD activity index in 64.7%; and 94.2% had active perianal disease activity index. A proportion of patients manifest abnormal C-reactive protein, erythrocyte sedimentation rate, platelet, hemoglobin and albumin. Conclusion: We suggest that patients with anal fistula associated to these clinical features should alert the medical team to the possibility of CD, which should be further investigated through endoscopy and imaging examination of alimentary tract to avoid the damage of anal function by routine anal fistula surgery.

RESUMO Racional: As características clínicas são fundamentais para melhorar a identificação e o tratamento da doença de Crohn (DC), de modo que a análise da amostra seja de grande valor. Objetivo: Explorar as características clínicas da DC fistulizante perianal. Métodos: Análise de 139 casos focados em seus dados clínicos. Resultados: A proporção de homens e mulheres foi de 3,3: 1; a média de idade de 28,2 anos; 47,5% dos pacientes tiveram fístula anal antes do diagnóstico de DC. Pacientes com cirurgia perianal prévia e medicação representaram 64,7% e 74,1%, respectivamente. O tipo de lesão L3 estava presente em 49,6% e os tipos B1 e B2, em 51,8% e 48,2%, respectivamente; fístula anal complexa foi diagnosticada em 90,6%. Sintomas de diarréia foram encontrados em 46% e lesões perianais isoladas em 29,5% dos pacientes. Valores anormais de IMC estavam presentes em 44,6%; índice de atividade DC ativa em 64,7%; e 94,2% tinham índice de atividade de doença perianal ativo. Proporção significativa de pacientes tinha proteína-C reativa, taxa de sedimenta do eritrócito, plaquetas hemoglobina e albumina anormais. Conclusão: Sugere-se que pacientes com fístula anal associada às essas características clínicas alertem a equipe médica para a possibilidade de DC, que deve ser investigada por endoscopia e exame de imagem do trato digestivo para evitar dano na função anal pela operação que rotineiramente é realizada no tratamento da fístula anal.

Total flavone of Abelmoschus manihot suppresses epithelial-mesenchymal transition via interfering transforming growth factor-ß1 signaling in Crohn's disease intestinal fibrosis.

AIM: To explore the role and mechanism of total flavone of Abelmoschus manihot (TFA) on epithelial-mesenchymal transition (EMT) progress of Crohn's disease (CD) intestinal fibrosis. METHODS: First, CCK-8 assay was performed to assess TFA on the viability of intestinal epithelial (IEC-6) cells and select the optimal concentrations of TFA for our further studies. Then cell morphology, wound healing and transwell assays were performed to examine the effect of TFA on morphology, migration and invasion of IEC-6 cells treated with TGF-ß1. In addition, immunofluorescence, real-time PCR analysis (qRT-PCR) and western blotting assays were carried out to detect the impact of TFA on EMT progress. Moreover, western blotting assay was performed to evaluate the function of TFA on the Smad and MAPK signaling pathways. Further, the role of co-treatment of TFA and si-Smad or MAPK inhibitors has been examined by qRT-PCR, western blotting, morphology, wound healing and transwell assays. RESULTS: In this study, TFA promoted transforming growth factor-ß1 (TGF-ß1)-induced (IEC-6) morphological change, migration and invasion, and increased the expression of epithelial markers and reduced the levels of mesenchymal markers, along with the inactivation of Smad and MAPK signaling pathways. Moreover, we revealed that si-Smad and MAPK inhibitors effectively attenuated TGF-ß1-induced EMT in IEC-6 cells. Importantly, co-treatment of TFA and si-Smad or MAPK inhibitors had better inhibitory effects on TGF-ß1-induced EMT in IEC-6 cells than either one of them. CONCLUSION: These findings could provide new insight into the molecular mechanisms of TFA on TGF-ß1-induced EMT in IEC-6 cells and TFA is expected to advance as a new therapy to treat CD intestinal fibrosis.

Effective and long-term outcome following ligation of the intersphincteric fistula tract (LIFT) for transsphincteric fistula.

OBJECTIVE: The purpose of this study was to evaluate the efficacy and long-term outcome of the ligation of the intersphincteric fistula tract (LIFT) procedure for transsphincteric fistula-in-ano. METHODS: A total of 43 patients that were treated with LIFT procedure and had a follow-up time of more than 1 year were included. RESULTS: The median age was 37.18 years, and 32 (74.4%) of the patients were male. The median follow-up time was 26.2 months (range 13-63 months). There were 29 (67.4%) uncomplicated transsphincteric fistulas, 10 (23.3%) horseshoe transsphincteric fistulas, and 4 (9.3%) multiple fistulas. Eight (18.5%) patients presented with dehiscence or infection at the intersphincteric wound and were successfully treated with either laying open (n = 5) or local application of silver nitrate (n = 3). The success rate, as determined from the last follow-up time point, was 83.7% (36/43). The mean time to complete failure was 8.6 weeks (range 1-28) in 7 patients. With the exception of these 7 patients, 32/36 (88.9%) patients had a Cleveland Clinic Florida Faecal incontinence score of 0, 3 patients had a score of 1, and 1 had a score of 2. No significant association was found between laying open and incontinence in these partial failure patients. CONCLUSION: The LIFT procedure can be considered an effective sphincter-sparing procedure in the management of transsphincteric fistula with an acceptable long-term outcome.