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Background/aim: This study was designed to identify the effect of pentoxifylline on trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats., Materials and Methods: Forty-two female Wistar rats were randomly divided into 7 groups: group A, TNBS + intraperitoneal (IP) pentoxifylline; group B, TNBS + IP saline; group C, TNBS + intrarectal (IR) pentoxifylline; group D, TNBS + IR saline; group E, IP pentoxifylline + TNBS; group F, IP saline + TNBS; group G, IR saline. Pentoxifylline was given daily for 3 days before or 6 days after the induction of colitis. Rats were killed after 6 days., Results: IP and IR pentoxifylline similarly and significantly reduced damage and histopathological scores. Pentoxifylline attenuated the accumulation of malonyldialdehyde and transforming growth factor β1 and the activities of myeloperoxidase, matrix metalloproteinase-3, and tissue inhibitor of metalloproteinases-1, and it also restored superoxide dismutase activity. The IP route was more effective than the IR route in this regard. Administration of IP pentoxifylline before or after induction did not influence all parameters. Conclusions: Pentoxifylline showed a therapeutic effect in this experimental colitis model. IP administration seemed to be better. This effect may occur as a result of inhibition of oxidative stress and metalloproteinase activity.

Background/aims: The Wnt/ß-catenin pathway plays a prominent role in hepatocellular carcinoma (HCC). The Dickkopf (DKK) proteins (DKK1-4) are known Wnt antagonists; the overexpression of DKK1 has been demonstrated in HCC, and increased DKK3 methylation in the HCC tissue is associated with worse prognosis. Thus, the aim of our study was to demonstrate the diagnostic accuracy of serum DKK1 and DKK3 in HCC in comparison with that of serum alpha-fetoprotein (AFP)., Materials and Methods: We included consecutive 40 HCC patients, 54 cirrhosis patients, and 39 healthy controls. Serum DKK1 and DKK3 levels were measured by an enzyme-linked immunosorbent assay, and serum AFP levels were measured by a chemiluminescence assay., Results: The AFP levels differed in each group and could help differentiate between groups (p < 0.001). The DKK1 levels could help differentiate the HCC group from cirrhosis and control groups (p < 0.001), and the DKK3 levels could help differentiate HCC and cirrhosis groups from the control group (p < 0.001). Combined usage of DKK1 and AFP increased the diagnostic yield, with a sensitivity, specificity, positive predictive value, and negative predictive value of 87.5%, 92.3%, 92.1%, and 87.8%, respectively., Conclusion: Although AFP is superior to DKK1 and DKK3 in the diagnosis of HCC, the combination of DKK1 and AFP showed a better diagnostic yield than AFP alone.

As a hepatotropic virus, hepatitis B virus (HBV) can establish a persistent chronic infection in the liver, termed, chronic hepatitis B (CHB), which causes a series of liver-related complications, including fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). HCC with HBV infection has a significantly increased morbidity and mortality, whereas it could be preventable. The current goal of antiviral therapy for HBV infection is to decrease CHB-related morbidity and mortality, and achieve sustained suppression of virus replication, which is known as a functional or immunological cure. The natural history of chronic HBV infection includes four immune phases: the immune-tolerant phase, immune-active phase, inactive phase, and reactivation phase. However, many CHB patients do not fit into any of these defined phases and are regarded as indeterminate. A large proportion of indeterminate patients are only treated with dynamic monitoring rather than recommended antiviral therapy, mainly due to the lack of definite guidelines. However, many of these patients may gradually have significant liver histopathological changes during disease progression. Recent studies have focused on the prevalence, progression, and carcinogenicity of indeterminate CHB, and more attention has been given to the prevention, detection, and treatment for these patients. Herein, we discuss the latest understanding of the epidemiology, clinical characteristics, and therapeutic strategies of indeterminate CHB, to provide avenues for the management of these patients. [ABSTRACT FROM AUTHOR]

Background and aims: Emergency endoscopic hemostasis for colonic diverticular bleeding is effective in preventing serious consequences. However, the low identification rate of the bleeding source makes the procedure burdensome for both patients and providers. We aimed to establish an efficient and safe emergency endoscopy system. Methods: We prospectively evaluated the usefulness of a scoring system (Jichi Medical University diverticular hemorrhage score: JD score) based on our experiences with past cases. The JD score was determined using four criteria: CT evidence of contrast agent extravasation, 3 points; oral anticoagulant (any type) use, 2 points; C-reactive protein ≥1 mg/dL, 1 point; and comorbidity index ≥3, 1 point. Based on the JD score, patients with acute diverticular bleeding who underwent emergency or elective endoscopy were grouped into JD ≥3 or JD <3 groups, respectively. The primary and secondary endpoints were the bleeding source identification rate and clinical outcomes. Results: The JD ≥3 and JD <3 groups included 35 and 47 patients, respectively. The rate of bleeding source identification, followed by the hemostatic procedure, was significantly higher in the JD ≥3 group than in the JD <3 group (77% vs. 23%, p <0.001), with a higher JD score associated with a higher bleeding source identification rate. No significant difference was observed between the groups in terms of clinical outcomes, except for a higher incidence of rebleeding at one-month post-discharge and a higher number of patients requiring interventional radiology in the JD ≥3 group than in the JD <3 group. Subgroup analysis showed that successful identification of the bleeding source and hemostasis contributed to a shorter hospital stay. Conclusion: We established a safe and efficient endoscopic scoring system for treating colonic diverticular bleeding. The higher the JD score, the higher the bleeding source identification, leading to a successful hemostatic procedure. Elective endoscopy was possible in the JD <3 group when vital signs were stable. [ABSTRACT FROM AUTHOR]

Caffeine (1,3,7-trimethylxanthine, also abbreviated to CAF) is a natural chemical with stimulant effects and is commonly included in many drinks and foods, including coffee, tea, cola, energy drinks, cocoa, chocolates, and so on. Our group previously reported that oral administration of CAF efficiently suppressed the development of intestinal inflammation in a dextran sulfate sodium (DSS)-induced murine acute colitis model by suppressing the expression of chitinase 3-like 1, one of the mammalian chitinases without enzymatic activity. Chitinases are hydrolytic enzymes that break down chitin, a polymer of N-acetylglucosamine, and chitinase-like proteins have no enzymatic activity with preserving chitin-binding ability. CAF binds a cleft of the chitinase active site and plays a role as a pan-chitinase inhibitor. Although CAF showed an anti-inflammatory effect in the above model, oral administration of low-dose CAF with 10% sucrose showed potentially neoplastic effects in colonic epithelial cells in a DSS-induced murine chronic colitis model. In this review, we would like to discuss the pros and cons of coffee/CAF in colonic inflammation and neoplasia with an example of pathological finding. [ABSTRACT FROM AUTHOR]

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Background: Although intestinal fibrosis is a consequence of recurrent inflammation in Inflammatory bowel disease (IBD), alleviating inflammation alone does not prevent the progression of fibrosis, suggesting that the development of direct anti-fibrotic agents is necessary. This study aimed to evaluate the anti-fibrotic properties of combination treatment with pentoxifylline (PTX) and vitamin E (Vit-E) on human primary intestinal myofibroblasts (HIMFs) and the therapeutic potential of the combination therapy in murine models of IBD. Methods: HIMFs were pretreated with PTX, Vit-E, or both, and incubated with TGF-β1. We performed Western blot, qPCR, collagen staining, and immunofluorescence to estimate the anti-fibrotic effects of PTX and Vit-E. The cytotoxicity of these was investigated through MTT assay. To induce murine models of IBD for in vivo study, C57BL/6 mice were treated with repeated cycles of dextran sulfate sodium (DSS), developing chronic colitis. We examined whether the combined PTX and Vit-E treatment would effectively ameliorate colonic fibrosis in vivo. Results: We found that the co-treatment with PTX and Vit-E suppressed TGF-β1-induced expression of fibrogenic markers, with decreased expression of pERK, pSmad2, and pJNK, more than either treatment alone in HIMFs. Neither PTX nor Vit-E showed any significant cytotoxicity in given concentrations. Consistently with the in vitro results, the co-administration with PTX and Vit-E effectively attenuated colonic fibrosis with recovery from thickening and shortening of colon in murine models of IBD. Conclusions: These findings demonstrated that the combination of PTX and Vit-E exhibits significant anti-fibrotic effects in both HIMFs and in vivo IBD models, providing a promising therapy for IBD. [ABSTRACT FROM AUTHOR]

Objective. We previously described that different concentration Nucleobindin-2 (NUCB2)/Nesfatin-1 gradients differently regulated visceral hypersensitivity in irritable bowel syndrome. Therefore, this study is aimed at evaluating the effect of NUCB2/Nesfatin-1 on model rats with chronic visceral hyperalgesia. Methods. Neonatal and mature Sprague-Dawley rats were randomly divided into the healthy control and chronic visceral hyperalgesia model groups. The model was built by combining maternal separation with the acetic acid enema. The models were identified by the distension volume threshold to reach abdominal withdraw reflex AWR score = 3 , histological staining, and myeloperoxidase (MPO) detection. The visceral sensitivity to chronic visceral hyperalgesia was then evaluated. Result. Rats in the model group responded more strongly to pulling stimulation than healthy controls; the distension volume threshold causing AWR3 response in model rats was lower than the control group before NUCB2/Nesfatin-1 intervention. After intervention, the distension volume threshold was significantly lower in the NUCB2/Nesfatin-1 central intervention group than in the NUCB2/Nesfatin-1 peripheral intervention group, and the peak value of external oblique muscle electrical activity was significantly higher. Additionally, compared with the male intervention group, in the female intervention group, the volume threshold was significantly lower and the peak value was higher. Conclusion. NUCB2/Nesfatin-1 could regulate visceral sensitivity in chronic visceral hyperalgesia model rats; its regulatory effect correlated with the type of NUCB2/Nesfatin-1 intervention approaches (central or peripheral) and sex (male or female). [ABSTRACT FROM AUTHOR]

Cholangiocarcinoma is an uncommon and highly aggressive biliary tract malignancy with few manifestations until late disease stages. Diagnosis is currently achieved through a combination of clinical, biochemical, radiological and histological techniques. A number of reported cancer biomarkers have the potential to be incorporated into diagnostic pathways, but all lack sufficient sensitivity and specificity limiting their possible use in screening and early diagnosis. The limitations of standard serum markers such as CA19-9, CA125 and CEA have driven researchers to identify multiple novel biomarkers, yet their clinical translation has been slow with a general requirement for further validation in larger patient cohorts. We review recent advances in the diagnostic pathway for suspected CCA as well as emerging diagnostic biomarkers for early detection, with a particular focus on non-invasive approaches. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is a highly fatal tumor which represents a major health problem worldwide. Due to asymptomatic nature of HCC, most patients present with the progressive stage of disease, so, unfortunately, there are no effective therapies. Existing techniques for HCC surveillance and diagnosis lack the required accuracy. Therefore, searching for new diagnostic and/or therapeutic tools could improve patient survival. This study aimed to estimate the diagnostic role of Dickkopf-1 (DKK1) and amphiregulin (AREG) and to find out their correlation with different clinicopathological parameters in HCC patients. Materials and Methods: Serum levels of DKK1 and AREG in 55 HCC patients, 20 cirrhotic patients, and 15 healthy subjects as control group were measured using the ELISA technique. Results: Both of DKK1 and AREG showed a significant increase in the HCC group compared to cirrhotic and healthy groups. DKK1 at a cutoff point of 8.92 ng/ml showed that the area under the curve (AUC) was 0.826 with 87.3% sensitivity and 82.9% specificity. DKK1 showed a significant correlation with tumor size, liver dysfunction, and poor performance status in HCC patients. AREG at a cutoff point of 8.74 pg/ml showed a sensitivity of 74.5% but low specificity (47.1%). AREG showed a significant correlation with portal vein thrombosis and tumor metastasis in HCC patients. Conclusion: Serum DKK1 could be a diagnostic biomarker for HCC. Both of DKK1 and AREG may play significant roles in tumor progression and may offer promising therapeutic targets in HCC patients. [ABSTRACT FROM AUTHOR]

Intestinal inflammation is the collective term for immune system-mediated diseases of unknown, multifactorial etiology, with often complex interactions between genetic and environmental factors. To mechanistically investigate the effect of treatment with compounds possessing immunomodulating properties in the context of intestinal inflammation, we developed an immunocompetent in vitro triculture intestinal model consisting of a differentiated intestinal epithelial layer (Caco-2/HT29-MTX) and immunocompetent cells (differentiated THP-1). The triculture mimicked a healthy intestine with stable barrier integrity. Lipopolysaccharide treatment triggered a controlled and reversible inflammatory state, resulting in significant impairment of barrier integrity and release of pro-inflammatory cytokines and chemokines, which are known hallmarks of intestinal inflammation. Treatment with known anti-inflammatory reference compounds (TPCA-1 and budenoside) prevented the induction of an inflammatory state; the decreasing triculture responses to this treatment measured by cytokine release, transepithelial electric resistance (TEER), and epithelial layer permeability proved the suitability of the intestinal model for anti-inflammatory drug screening. Finally, selected tobacco alkaloids (nicotine and anatabine (R / S and S forms)) were tested in the in vitro triculture for their potential anti-inflammatory properties. Indeed, naturally occurring alkaloids, such as tobacco-derived alkaloids, have shown substantial anti-inflammatory effects in several in vitro and in vivo models of inflammation, gaining increasing interest. Similar to the anti-inflammatory reference compounds, one of the tobacco alkaloids under investigation partially prevented the decrease in the TEER and increase in permeability and reduced the release of pro-inflammatory cytokines and chemokines. Taken together, these data confirm that our in vitro model is suitable for screening potential anti-inflammatory compounds in the context of intestinal inflammation. [ABSTRACT FROM AUTHOR]