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Background: Comorbidity of Opisthorchis viverrini (OV) infection and nonalcoholic fatty-liver disease (NAFLD) enhances NAFLD progression to nonalcoholic steatohepatitis (NASH) by promoting severe liver inflammation and fibrosis. Here, we investigated the effect of supplementation with curcumin-loaded nanocomplexes (CNCs) on the severity of NASH in hamsters. Methodology: Hamsters were placed in experimental groups as follows: fed standard chow diet (normal control, NC); fed only high-fat and high-fructose (HFF) diet; O. viverrini-infected and fed HFF diet (HFFOV); group fed with blank nanocomplexes (HFFOV+BNCs); groups fed different doses of CNCs (25, 50 and 100 mg/kg body weight: HFFOV+CNCs25; HFFOV+CNCs50; HFFOV+CNCs100, respectively) and a group given native curcumin (HFFOV+CUR). All treatment were for three months. Results: The HFF group revealed NAFLD as evidenced by hepatic fat accumulation, ballooning, mild inflammation and little or no fibrosis. These changes were more obvious in the HFFOV group, indicating development of NASH. In contrast, in the HFFOV+CNCs50 group, histopathological features indicated that hepatic fat accumulation, cell ballooning, cell inflammation and fibrosis were lower than in other treatment groups. Relevantly, the expression of lipid-uptake genes, including fatty-acid uptake (cluster of differentiation 36), was reduced, which was associated with the lowering of alanine aminotransferase, total cholesterol and triglyceride (TG) levels. Reduced expression of an inflammation marker (high-mobility group box protein 1) and a fibrosis marker (alpha smooth-muscle actin) were also observed in the HFFOV+CNCs50 group. Conclusion: CNCs treatment attenuates the severity of NASH by decreasing hepatic steatosis, inflammation, and fibrosis as well as TG synthesis. CNCs mitigate the severity of NASH in this preclinical study, which indicates promise for future use in patients. [ABSTRACT FROM AUTHOR]

Background: Opisthorchis viverrini (O. viverrini, Ov) infection and consumption of high-fat and high-fructose (HFF) diet exacerbate liver and kidney disease. Here, we investigated the effects of a combination of O. viverrini infection and HFF diet on kidney pathology via changes in the gut microbiome and host proteome in hamsters. Methodology/Principal findings: Twenty animals were divided into four groups; 1) fed a normal diet not infected with O. viverrini (normal group), 2) fed an HFF diet and not infected with O. viverrini (HFF), 3) fed a normal diet and infected with O. viverrini (Ov), and 4) fed an HFF diet and infected with O. viverrini (HFFOv). DNA was extracted from fecal samples and the V3–V4 region of the bacterial 16S rRNA gene sequenced on an Illumina MiSeq sequencing platform. In addition, LC/MS-MS analysis was done. Histopathological studies and biochemical assays were also conducted. The results indicated that the HFFOv group exhibited the most severe kidney injury, manifested as elevated KIM-1 expression and accumulation of fibrosis in kidney tissue. The microbiome of the HFFOv group was more diverse than in the HFF group: there were increased numbers of Ruminococcaceae, Lachnospiraceae, Desulfovibrionaceae and Akkermansiaceae, but fewer Eggerthellaceae. In total, 243 host proteins were identified across all groups. Analysis using STITCH predicted that host proteome changes may lead to leaking of the gut, allowing molecules such as soluble CD14 and p-cresol to pass through to promote kidney disease. In addition, differential expression of TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 (Tab2, involving renal inflammation and injury) are predicted to be associated with kidney disease. Conclusions/Significance: The combination of HFF diet and O. viverrini infection may promote kidney injury through alterations in the gut microbiome and host proteome. This knowledge may suggest an effective strategy to prevent kidney disease beyond the early stages. [ABSTRACT FROM AUTHOR]

Cholangiocarcinoma (CCA) is often diagnosed late, leading to incomplete tumor removal, drug resistance and reduced chemotherapy efficacy. Curcumin has the potential for anti-cancer activity through various therapeutic properties and can improve the efficacy of chemotherapy. We aimed to investigate the synergistic effect of a combination of curcumin and gemcitabine against CCA, targeting the LAT2/glutamine pathway. This combination synergistically suppressed proliferation in gemcitabine-resistant CCA cells (KKU-213BGemR). It also resulted in a remarkable degree of CCA cell apoptosis and cell cycle arrest, characterized by a high proportion of cells in the S and G2/M phases. Knockdown of SLC7A8 decreased the expressions of glutaminase and glutamine synthetase, resulting in inhibited cell proliferation and sensitized CCA cells to gemcitabine treatment. Moreover, in vivo experiments showed that a combination curcumin and gemcitabine significantly reduced tumor size, tumor growth rate and LAT2 expression in a gemcitabine-resistant CCA xenograft mouse model. Suppression of tumor progression in an orthotopic CCA hamster model provided strong support for clinical application. In conclusion, curcumin synergistically enhances gemcitabine efficacy against gemcitabine-resistant CCA by induction of apoptosis, partly via inhibiting LAT2/glutamine pathway. This approach may be an alternative strategy for the treatment of gemcitabine-resistant in CCA patients. [ABSTRACT FROM AUTHOR]

Background: Curcumin-loaded nanocomplexes (CNCs) previously demonstrated lower toxicity and extended release better than is the case for free curcumin. Here, we evaluated the efficacy of CNCs against opisthorchiasis-associated cholangiocarcinoma (CCA) in hamsters. Method: Dose optimization (dose and frequency) was performed over a 1-month period using hamsters, a model that is widely used for study of opisthorchiasis-associated cholangiocarcinoma. In the main experimental study, CCA was induced by a combination of fluke, Opisthorchis viverrini (OV), infection and N-nitrosodimethylamine (NDMA) treatment. Either blank (empty) nanocomplexes (BNCs) or different concentrations of CNCs (equivalent to 10 and 20 mg cur/kg bw) were given to hamsters thrice a week for 5 months. The histopathological changes, biochemical parameters, and the expression of inflammatory/oncogenic transcription factors were investigated. In addition, the role of CNCs in attenuating CCA genesis, as seen in an animal model, was also confirmed in vitro using CCA cell lines. Results: The optimization study revealed that treatment with CNCs at a dose equivalent to 10 mg cur/kg bw, thrice a week for 1 month, led to a greater reduction of inflammation and liver injury induced in hamsters by OV + NDMA than did treatments at other dose rates. Oral administration with CNCs (10 mg cur/kg bw), thrice a week for 5 months, significantly increased survival rate, reduced CCA incidence, extent of tumor development, cholangitis, bile duct injury and cholangiofibroma. In addition, this treatment decreased serum ALP and ALT activities and suppressed expression of NF-κB, FOXM1, HMGB1, PCNA and formation of 8-nitroguanine. Treatment of CCA cell lines with CNCs also reduced cell proliferation and colony formation, similar to those treated with NF-κB and/or FOXM1 inhibitors. Conclusion: CNCs (10 mg cur/kg bw) attenuate the progression of fluke-related CCA in hamsters partly via a NF-κB and FOXM1-mediated pathway. [ABSTRACT FROM AUTHOR]

Background: Several studies have demonstrated that helminth infections provide a degree of protection against Type 2 diabetes mellitus (T2DM). However, the relationship between Strongyloides stercoralis infection and T2DM has scarcely been investigated and the protective effect of infection against development of diabetic complications is unclear. In this study, we aimed to investigate the relationship between S. stercoralis infection and T2DM in a rural area of Khon Kaen Province, Thailand. The impact of S. stercoralis infection on diabetic complication-related kidney function biochemical parameters and body-mass index (BMI) was also assessed. Methodology: Using a cross-sectional study design, S. stercoralis infection and T2DM assessments were conducted between October 2020 and May 2021. Associations between S. stercoralis infection, T2DM, and socioeconomic factors were analyzed using multivariable logistic regression analyses. Diabetic complication-related biochemical parameters relating largely to kidney function (estimated glomerular filtration rate (eGFR), urine albumin-to-creatinine ratio (UACR), serum creatinine, uric acid, alanine transaminase (ALT), and low-density lipoprotein cholesterol (LDL-C)) and BMI of participants with and without T2DM were compared between groups with or without S. stercoralis infection. Results: One hundred and seven out of 704 individuals (15.20%) were positive for S. stercoralis, and 283 people were diagnosed with T2DM. Of those with T2DM, 11.31% (32/283) were infected with S. stercoralis and of those without T2DM, 17.82% (75/421) were infected with S. stercoralis. Multivariate analysis revealed that T2DM was inversely correlated with S. stercoralis infection (Adjusted OR = 0.49; 95% CI: 0.30, 0.78; p = 0.003), while male, increasing age, lower education level, and alcohol intake were positively associated with infection. Those infected with S. stercoralis had lower eGFR levels and higher ALT and UACR levels than those in the uninfected group. Conclusion: This finding indicates that S. stercoralis infection was inversely associated with T2DM in northeastern Thailand, but participants infected with S. stercoralis had lower eGFR levels and higher ALT and UACR levels. Infection with S. stercoralis might lead to worse complication-related renal biochemical parameters. [ABSTRACT FROM AUTHOR]

In the Human ethical statement subsection of Materials and methods, there is an error in first sentence. The correct sentence is: This study was approved by the human ethical review committee of Khon Kaen University, Thailand (HE631673) following the principles of the Declaration of Helsinki.By Manachai Yingklang; Apisit Chaidee; Rungtiwa Dangtakot; Chanakan Jantawong; Ornuma Haonon; Chutima Sitthirach; Nguyen Thi Hai; Ubon Cha'on; Sirirat Anutrakulchai; Supot Kamsa-ard and Somchai PinlaorReported by Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author [Extracted from the article]