Effects of thymidine phosphorylase on tumor aggressiveness and 5-fluorouracil sensitivity in cholangiocarcinoma

AIM: To evaluate the role of thymidine phosphorylase (TP) in cholangiocarcinoma using small interfering RNA (siRNA). METHODS: A human cholangiocarcinoma-derived cell line KKU-M139, which has a naturally high level of endogenous TP, had TP expression transiently knocked down using siRNA. Cell growth, migration, in vitro angiogenesis, apoptosis, and cytotoxicity were assayed in TP knockdown and wild-type cell lines. RESULTS: TP mRNA and protein expression were decreased by 87.1% ± 0.49% and 72.5% ± 3.2%, respectively, compared with control cells. Inhibition of TP significantly decreased migration of KKU-M139, and suppressed migration and tube formation of human umbilical vein endothelial cells. siRNA also reduced the ability of TP to resist hypoxia-induced apoptosis, while suppression of TP reduced the sensitivity of KKU-M139 to 5-fluorouracil. CONCLUSION: Inhibition of TP may be beneficial in decreasing angiogenesis-dependent growth and migration of cholangiocarcinoma but may diminish the response to 5-fluorouracil chemotherapy.

Examining ecosystem(dis-)services on liver fluke infection in rural Northeast Thailand

Background The direct reliance of humans on and their interactions with freshwater ecosystems in the Lower Mekong Basin have given rise to parasitic infections,which is particularly prevalent in Northeast Thailand where raw fish consumption is practiced.This study examined the interactions between environments,ecosystem(dis-)services,human raw fish consumption habits,and raw fish dish sharing on liver fluke infection risk.Method Water fecal contents and the first intermediate snail host were sampled between June and September of 2019.One hundred twenty questionnaires were surveyed in two villages of different environmental surroundings,one next to a river and the other located inland,in Northeast Thailand.Multivariate regression analyses using linear mixed effect models assessed the influence of social,behavioral and perceptual factors on raw fish consumption frequency,willingness to avoid consumption and liver fluke infection status.Social network analysis compared the degree of raw fish dish sharing between the villages and assessed the probable influence of connections to fish procurement locations and sharing activities on liver fluke infection risk.Results High abundance of the first intermediate snail host and presence of fecal contamination in water could endanger both villages to ecosystem disservices of parasitic transmission.The river-side village relied more on provisioning ecosystem services than the inland village(29.7%vs.16.1%of villages)to consume raw fish as their main source of protein.Males in both villages(64.5 and 40.4 days/year for the respective villages)are also likely to consume koi pla and pla som,higher risk fish dishes,more frequently than females(4.1 and 4.3 days/year for the respective villages).The consumption habits of both villages were driven mostly by deriving cultural ecosystem services.Participation in raw fish dish sharing activities significantly reduced the odds of an individual being willing to avoid the consumption(Odds ratio=0.19).Network analysis suggested that river-side villagers had a more direct raw fish dish sharing interaction and they procured fish from multiple locations;these characteristics might potentially account for more liver fluke infected households in the village.Conclusion Villagers’raw fish consumption is driven by deriving cultural ecosystem services,and the geographic settings of the villages potentially affect villagers’fish procurement locations and infection risk.The findings underscore the linkages between villagers and their surrounding ecosystem environments as pertinent determinants for foodborne parasitic disease risk.

Children education for sustainable control of liverfluke infections

Significant disease burden is caused by infections with human liver flukes, includingClonorchis sinensis,Opisthorchis viverrini andO. felineus. Epidemiology is characterized by high burden in the male than the female, and in the elder than the younger. Chemotherapy is the mainstream for morbidity control, but it could not prevent re-infection. Mean-while, behavioral change on the dietary habit of ingesting raw freshwater fish is challenging. In this opinion, we argue why it is important to educate children for sustainable control of liver fluke infections. Then, the design, development and key messages of an educational cartoon for preventing liver fluke infections is introduced. Technical focuses are emphasized based on a pilot using the education cartoon for preventing clonorchiasis in China. Finally, how to further develop and verify this education strategy is discussed.

Accuracy of a new rapid diagnostic test for urinary antigen detection and assessment of drug treatment in opisthorchiasis

Background Screening for opisthorchiasis,a parasitic worm infection affecting many millions of people in Southeast Asia,has traditionally relied on faecal egg examination such as the formalin-ethyl acetate concentration technique(FECT)and Kato-Katz method.Although the urinary enzyme-linked immunosorbent assay(ELISA)has been used more recently,we developed a urinary antigen-based rapid diagnostic test(RDT)to simplify diagnosis and as a point-of-care testing(POCT)and field applications for surveillance and control of opisthorchiasis.Methods A urinaryOpisthorchis viverrini(OV)-RDT was developed using immunochromatographic methodology with a specific monoclonal antibody against OV.The diagnostic performance of the urinary OV-RDT was compared to that of quantitative faecal FECT and urinary antigen ELISA(n=493).Cross-reactivities of urinary OV-RDT with other helminthiases coexisted withO.viverrini were determined(n=96).A field trial in the application of urinary OV-RDT was compared with urinary antigen ELISA at baseline screening and assessment of drug treatment outcomes in opisthorchiasis(n=1629).The McNemar chi-square,Kruskal-Wallis and Cohen’s kappa coefficient(κ-value)tests were used for statistical analyses.Results Urinary OV-RDT had sensitivity of 94.2%and specificity of 93.2%,compared to faecal FECT.Urinary OV-RDT had high diagnostic agreement(Kappa=0.842-0.874,P<0.001)and quantitative correlation with urinary antigen ELISA(Kruskal-Wallis tests=316.2,P<0.0001)and faecal FECT(Kruskal-Wallis tests=362.3,P<0.0001).The positive rates by OV-RDT,ELISA and FECT were 48.9%,52.5%and 49.3%,respectively.Cross-reactions of urinary OV-RDT with other helminthiases were few(2%).Field trials of urinary OV-RDT yielded comparable prevalence ofO.viverrini between urinary OV-RDT(53.2%)and urinary antigen ELISA(54.0%).OV screening showed high diagnostic agreement(kappa>0.8,P<0.0001)between urinary OV-RDT and urinary antigen ELISA.The cure rates of opisthorchiasis at 1 month post-praziquantel treatment determined by urinary OV-RDT(86.6%)and urinary antigen ELISA(80.5%)were similar(P>0.05).Conclusions The urinary OV-RDT test has high potential as a new tool for screening and evaluating treatment outcomes in opisthorchiasis.The ease of sample collection and simplicity of urinary OV-RDT may facilitate mass screening,control and elimination of opisthorchiasis,thereby contributing to a reduction in the disease burden in Southeast Asia.