Apisit Chaidee

Introduction: Strongyloides stercoralis exacerbates the early stages of chronic kidney disease (CKD) through the disruption of metabolic processes. However, the metabolic consequences of infection and of its resolution after treatment remain poorly characterized. This study explores urinary metabolic changes in patients with early-stage CKD following antiparasitic therapy. Methods: In an exploratory before-and-after longitudinal study design, fifteen patients presenting with concurrent early-stage CKD (stages 1–3) and confirmed strongyloidiasis were monitored at baseline and 17 months following ivermectin anthelmintic treatment. Serum and urine clinical biochemistry assessments were paired with high-resolution untargeted liquid chromatography-quadrupole time-of-flight mass spectrometry (LC/Q-TOF MS) urinary metabolomic profiling executed in both negative and positive ionization modes. Results: Global multivariate analyses did not demonstrate statistically significant separation between pre- and post-treatment urinary metabolomic profiles. However, univariate analyses identified 91 significantly altered urinary mass features following treatment. Among these, thirteen metabolites (twelve decreased and one increased) were identified as potential markers associated with parasite clearance in patients with CKD. Changes in fasting blood sugar, serum creatinine, and estimated glomerular filtration rate (eGFR) were also observed. Notably, urinary 1-O-galloyl-6-O-cinnamoylglucose was negatively correlated with urine creatinine, while sedoheptulose-7-phosphate levels was negatively correlated with serum creatinine. Additionally, urinary ascorbic acid levels increased following treatment, suggesting their potential relevance to kidney function. Pathway analysis indicated disturbances in amino acid and carbohydrate metabolism, particularly glycine/serine metabolism, tyrosine metabolism, and glycolysis, that partially normalized post-treatment. Conclusion: These findings suggest that clearance of S. stercoralis infection was associated with changes in urinary metabolomic profiles in patients with CKD. Kidney function and urinary metabolomic profiles were observed in patients with early-stage CKD and S. stercoralis infection. Further investigations of kidney outcomes following S. stercoralis clearance and of the potential value of strongyloidiasis screening in patients with CKD are warranted.

Background: Cholangiocarcinoma (CCA) is a deadly cancer often detected late. Current diagnostic methods, such as ultrasound and invasive biopsies, have limitations; there is a critical need for a rapid, minimally invasive and effective strategy for the early diagnosis and staging of CCA. Methods: We aimed to address this need using serum samples and label-free surface-enhanced Raman spectroscopy (SERS) combined with machine learning. CCA development was induced in hamsters using a combination of Opisthorchis viverrini infection and administration of N -nitrosodimethylamine, with induction time courses spanning 1–5 month(s). Normal and pathological stages (inflammation, precancerous lesion, and CCA) were assigned based on histopathological features, as well as the expression of cytokeratin 19 and alpha-fetoprotein. Raman spectra were subjected to dimensionality reduction using principal component analysis, and diagnostic clusters were acquired using partial least-squares discriminant analysis. Results: Histopathological analysis confirmed a clear path towards CCA, initiated by marked inflammation, progressing to include significant cholangiofibrosis and cholangiofibroma in the precancerous stage, and culminating in definitive CCA tumor development. The integration of SERS and machine learning achieved a diagnostic sensitivity of 93%, specificity of 95%, and accuracy of ≥ 67% for precancerous lesions and CCA, with an area under the receiver operating characteristic curve exceeding 0.67. Conclusions: Our findings demonstrate that this cost-effective, label-free SERS approach can accurately detect precancerous and cancerous stages of cholangiocarcinoma in a hamster model, highlighting its strong potential for future development as a community-based screening tool.

A recent study in hamsters showed that infection with the liver fluke Opisthorchis viverrini in diabetic hosts worsens the severity of hepatobiliary disease. However, the effects of diabetes on the worm’s phenotype and gene expression pattern remain unknown. This study investigated the impact of diabetes on the global gene expression and development of O. viverrini in diabetic hamsters. Parasitological parameters were assessed, and mRNA sequencing with bioinformatic analysis was performed. The study revealed that worm establishment rates in diabetic hamsters were directly correlated with fasting plasma glucose levels. Interestingly, worms collected from diabetic hosts exhibited stunted growth and reduced egg production. Transcriptomic analysis revealed significant alterations in gene expression, with 4314 and 567 differentially expressed genes at 21- and 35-days post-infection, respectively. Gene ontology enrichment analysis highlighted changes in biological processes related to stress response, metabolism, and cellular organization. Notably, genes associated with parasite virulence, including granulin, tetraspanins, and thioredoxins, showed significant upregulation in diabetic hosts. These findings demonstrate the profound impact of host diabetic status on O. viverrini development and gene expression, providing insights into the complex interplay between host metabolism and parasite biology, including molecular adaptations of O. viverrini in hosts. This study contributes to our understanding of opisthorchiasis in the context of metabolic disorders and may inform future strategies for disease management in diabetic human populations.

Background: Comorbidity ofOpisthorchis 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.

Background: Strongyloides stercoralis infection typically causes severe symptoms in immunocompromised patients. This infection can also alter the gut microbiota and is often found in areas where chronic kidney disease (CKD) is common. However, the relationship between S. stercoralis and the gut microbiome in chronic kidney disease (CKD) is not understood fully. Recent studies have shown that gut dysbiosis plays an important role in the progression of CKD. Hence, this study aims to investigate the association of S. stercoralis infection and gut microbiome in CKD patients. Methodology/Principal findings: Among 838 volunteers from Khon Kaen Province, northeastern Thailand, 40 subjects with CKD were enrolled and divided into two groups (S. stercoralis-infected and -uninfected) matched for age, sex and biochemical parameters. Next-generation technology was used to amplify and sequence the V3-V4 region of the 16S rRNA gene to provide a profile of the gut microbiota. Results revealed that members of the S. stercoralis-infected group had lower gut microbial diversity than was seen in the uninfected group. Interestingly, there was significantly greater representation of some pathogenic bacteria in the S. stercoralis-infected CKD group, including Escherichia-Shigella (P = 0.013), Rothia (P = 0.013) and Aggregatibacter (P = 0.03). There was also a trend towards increased Actinomyces, Streptococcus and Haemophilus (P > 0.05) in this group. On the other hand, the S. stercoralis-infected CKD group had significantly lower representation of SCFA-producing bacteria such as Anaerostipes (P = 0.01), Coprococcus_1 (0.043) and a non-significant decrease of Akkermansia, Eubacterium rectale and Eubacterium hallii (P > 0.05) relative to the uninfected group. Interesting, the genera Escherichia-Shigella and Anaerostipes exhibited opposing trends, which were significantly related to sex, age, infection status and CKD stages. The genus Escherichia-Shigella was significantly more abundant in CKD patients over the age of 65 years and infected with S. stercoralis. A correlation analysis showed inverse moderate correlation between the abundance of the genus of Escherichia-Shigella and the level of estimated glomerular filtration rate (eGFR). Conclusions/Significance: Conclusion, the results suggest that S. stercoralis infection induced gut dysbiosis in the CKD patients, which might be involved in CKD progression.

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.