The egg ribonuclease SjCP1412 accelerates liver fibrosis caused by Schistosoma japonicum infection involving damage-associated molecular patterns (DAMPs).

Schistosomiasis, a parasite infectious disease caused by Schistosoma japonicum, often leads to egg granuloma and fibrosis due to the inflammatory reaction triggered by egg antigens released in the host liver. This study focuses on the role of the egg antigens CP1412 protein of S. japonicum (SjCP1412) with RNase activity in promoting liver fibrosis. In this study, the recombinant egg ribonuclease SjCP1412, which had RNase activity, was successfully prepared. By analysing the serum of the population, it has been proven that the anti-SjCP1412 IgG in the serum of patients with advanced schistosomiasis was moderately correlated with liver fibrosis, and SjCP1412 may be an important antigen associated with liver fibrosis in schistosomiasis. In vitro, the rSjCP1412 protein induced the human liver cancer cell line Hep G2 and liver sinusoidal endothelial cells apoptosis and necrosis and the release of proinflammatory damage-associated molecular patterns (DAMPs). In mice infected with schistosomes, rSjCP1412 immunization or antibody neutralization of SjCP1412 activity significantly reduced cell apoptosis and necroptosis in liver tissue, thereby reducing inflammation and liver fibrosis. In summary, the SjCP1412 protein plays a crucial role in promoting liver fibrosis during schistosomiasis through mediating the liver cells apoptosis and necroptosis to release DAMPs inducing an inflammatory reaction. Blocking SjCP1412 activity could inhibit its proapoptotic and necrotic effects and alleviate hepatic fibrosis. These findings suggest that SjCP1412 may be served as a promising drug target for managing liver fibrosis in schistosomiasis japonica.

Schistosomicidal effects of histone acetyltransferase inhibitors against Schistosoma japonicum juveniles and adult worms in vitro.

BACKGROUND: Schistosomiasis is a relatively neglected parasitic disease that afflicts more than 250 million people worldwide, for which the control strategy relies mainly on mass treatment with the only available drug, praziquantel (PZQ). This approach is not sustainable and is a priority for developing novel drug candidates for the treatment and control of schistosomiasis. METHODOLOGYS/PRINCIPAL FINDINGS: In our previous study, we found that DW-3-15, a kind of PZQ derivative, could significantly downregulate the expression of the histone acetyltransferase of Schistosoma japonicum (SjHAT). In this study, several commercially available HAT inhibitors, A485, C646 and curcumin were screened in vitro to verify their antischistosomal activities against S. japonicum juveniles and adults. Parasitological studies and scanning electron microscopy were used to study the primary action characteristics of HAT inhibitors in vitro. Quantitative real-time PCR was employed to detect the mRNA level of SjHAT after treatment with different HAT inhibitors. Our results demonstrated that curcumin was the most effective inhibitor against both juveniles and adults of S. japonicum, and its schistosomicidal effects were time- and dose dependent. However, A485 and C646 had limited antischistosomal activity. Scanning electron microscopy demonstrated that in comparison with DW-3-15, curcumin caused similar tegumental changes in male adult worms. Furthermore, both curcumin and DW-3-15 significantly decreased the SjHAT mRNA level, and curcumin dose-dependently reduced the SjHAT expression level in female, male and juvenile worms. CONCLUSIONS: Among the three commercially available HATs, curcumin was the most potent against schistosomes. Both curcumin and our patent compound DW-3-15 markedly downregulated the expression of SjHAT, indicating that SjHAT may be a potential therapeutic target for developing novel antischistosomal drug candidates.

[Optimization of time of artificial population schistosome infected Oncomelania hupensis snails].

OBJECTIVE: To explore the optimizational time of artificial population schistosome infected Oncomelania hupensis snails. METHODS: Under laboratory conditions, the snails were infected with the miracidia of Schistosoma japonicum for 2 h, 3 h and 4 h respectively, and the death rates and the infection rates of the snails, and the quantities of cercariae of each group were observed 60-120 d after the infection, and all the data observed were analyzed to get the optimizational time of artificial population schistosome infected snails. RESULTS: Of the 3 h group, the snail infection rate was the highest and the mortality was the lowest among the 3 groups (P<0.05). The average number of cercariae of the 3 h group was higher than that of the 2 h group (P<0.05), while there was no statistical difference between the 3 h group and the 4h group (P>0.05). CONCLUSION: Under laboratory conditions, the optimizational time is 3 h in artificial population schistosome infected O. hupensis snails.

[Technology of preventing oncomelania snail diffusion in east route of South-to-North Water Diversion Project II. Effect of sand buried and reed protection on snail control in area of water source].

OBJECTIVE: To evaluate the effect of sand buried and reed protection on Oncomelania snail control in the area of water source of the east route of South-to-North Water Diversion Project. METHODS: The Oncomelania snail eggs were counted after the snails raised seven days in the sand of different contents in the spawning period. The survival of the snails was observed when the snails were raised on the sand surface in the laboratory. The change of the densities of living snails and reed growth were observed in the area of water source. RESULTS: The snails did not lay eggs in the pure sand environment. There was a negative correlation between the number of snail eggs and the content of sand (r = -0.965, P = 0.008). The mortality rates of the snails were increasing with the increase of the time in the sand environment. The mortality rates of the snails were 96.00% and 100% when the snails were raised 3 months and 6 months around 25 degrees C respectively. The field test showed that the snails were not discovered after the sand buried, the second spring, after the flood season, and the third spring. However, the density of living snails of the control group dropped by 93.65% 2 weeks after using molluscicide, but increased by 100% and kept in 0.37 snails/0.1 m2 after the flood season and the third year spring, respectively. The reed growth was good in the second spring after the sand buried. CONCLUSIONS: The sand environment is unfavorable for laying eggs and survival of the snails. The sand buried method has the effects of snail control and reed protection. In addition, the method could also prevent the snail spread in the flood season.

A randomized double-blind, positive-control trial of topical thalidomide in erosive oral lichen planus.

OBJECTIVE: The objective of this study was to evaluate the short-term efficacy and safety of topical thalidomide for erosive oral lichen planes (OLP) in a prospective randomized, positive-control, double-blind clinical trial. STUDY DESIGN: Sixty-nine patients with erosive OLP received thalidomide 1% paste (n = 37) or dexamethasone 0.043% paste (n = 32) for 1 week. Patients without erosions after initial 1-week treatment were followed for recurrence, whereas those with ongoing erosions received an additional 3-week treatment. Outcome measures included size of erosive area, visual analog scale (VAS) scores, 3-month recurrence rates, and adverse effects at 1 year. RESULTS: After 1-week application, both groups showed significant reductions in erosive areas and VAS scores (P < .001). Complete healing occurred in 18 (54.5%) of 33 thalidomide-treated and 17 (56.7%) of 30 dexamethasone-treated patients. Erosive area size (P = .420) and VAS scores (P = .498) were similar between groups. After 1 month of treatment, 24 patients receiving thalidomide (66.7%) and 22 receiving dexamethasone (73.3%) fully healed. There was no difference between groups in recurrence at the 3-month follow-up. Only 2 patients in each group experienced discomfort with treatment, and no adverse reactions were observed over 1 year of follow-up. CONCLUSION: Topical thalidomide appears as effective as dexamethasone for erosive OLP.