dAcanthamoeba sp. parasites are the causative agents of Acanthamoeba keratitis, fatal granulomatous amoebic encephalitis, and cutaneous infections. However, there are currently no effective drugs for these organisms. Here, we evaluated the activity of the antimalarial agent artemether against Acanthamoeba castellanii trophozoites and identified potential targets of this agent through a proteomic approach. Artemether exhibited in vitro amoebicidal activity in a time-and dose-dependent manner and induced ultrastructural modification and cell apoptosis. The iTRAQ quantitative proteomic analysis identified 707 proteins that were differentially expressed after artemether treatment. We focused on phosphoglycerate dehydrogenase and phosphoserine aminotransferase in the serine biosynthesis pathway because of their importance to the growth and proliferation of protozoan and cancer cells. The expression of these proteins in Acanthamoeba was validated using quantitative real-time PCR and Western blotting after artemether treatment. The changes in the expression levels of phosphoserine aminotransferase were consistent with those of phosphoglycerate dehydrogenase. Therefore, the downregulation of phosphoserine aminotransferase may be due to the downregulation of phosphoglycerate dehydrogenase. Furthermore, exogenous serine might antagonize the activity of artemether against Acanthamoeba trophozoites. These results indicate that the serine biosynthesis pathway is important to amoeba survival and that targeting these enzymes would improve the treatment of Acanthamoeba infections. Artemether may be used as a phosphoglycerate dehydrogenase inhibitor to control or block Acanthamoeba infections.
Babesia species are tick-borne intraerythrocytic protozoa that cause babesiosis in humans worldwide. No vaccine has yet proven effective against Babesia infection. Surface antigens of merozoites are involved in the invasion of erythrocytes by Babesia. Surface antigens may be presented by both babesial sporozoites and merozoites and provide a general target for antibody-mediated inhibition of erythrocyte invasion. Here we evaluated a major surface antigen of B. microti merozoites, BMSA, as a potential vaccine to prevent babesiosis. Our data indicated that bmsa is transcribed during different phases, including ring form, amoeboid form, and merozoites, and that its expression is significantly increased in mature merozoites. The protein was found to be located in the membrane of B. microti and in the cytoplasm of infected erythrocytes. The immune response induced by BMSA had a significant inhibitory effect on parasite invasion of the host erythrocytes (83.3% inhibition of invasion) and parasite growth in vivo. The levels of parasitemia significantly decreased after BMSA vaccination when mice were infected with babesia parasite. Importantly, protective immunity was significantly related to the upregulation of the Th17 cytokine interleukin-17, the Th1 cytokine interleukin-12p70 and the Th2 cytokines, such as interleukin-4, -6, and -10. Ingenuity Pathway Analysis indicated that interleukin-17 facilitated the secretion of Th2 cytokines, such as interleukin-10, -4, and -6, thereby inducing a predominately Th2 protective immune response and promoting the expression a high level of special IgG1 against Babesia infection. Further, an anti-BMSA monoclonal antibody successfully protected NOD/SCID mice from a challenge with B. microti. Taken together, our results indicated that BMSA induces a protective immune response against Babesia infection and may serve as a potential vaccine.
Background. Zhengqing Fengtongning release tablet (ZQFTN) is a proprietary Chinese medicine preparation of sinomenine, the main active component of the traditional Chinese medicine (TCM) Sinomenium acutum. It is used in China as a complementary and alternative medicine (CAM) for knee osteoarthritis (KOA). The objective of this study was to evaluate the clinical efficacy and safety of ZQFTN in KOA treatment. Method. Randomized controlled trials of ZQFTN in KOA treatment were searched in PubMed, Cochrane Library, China National Knowledge Infrastructure, Chinese Scientific Journals Database, and Wanfang database. Two reviewers independently conducted the screening, extracted the data, and assessed the methodological quality. Statistical analysis was performed using RevMan 5.3 software. Results. Eighteen studies were assessed that included 1512 participants (757 in the treatment group and 755 in the control group). The results showed that compared with the control group, the Visual Analogue Scale (standardized mean difference (SMD) = −0.87, 95% confidence interval (CI): [−1.08, −0.66], P < 0.001 ), Western Ontario and Mc Master University (WOMAC) Osteoarthritis Index pain score (SMD = −0.67, 95% CI: [−0.88, −0.46], P < 0.001 ), WOMAC stiffness score (SMD = −0.53, 95% CI: [−0.86, −0.20], P = 0.001 ), WOMAC function score (SMD = −0.76, 95% CI: [−0.97, −0.55], P < 0.001 ), serum interleukin-1β level (SMD = −4.36, 95% CI: [−6.41, −2.31], P < 0.001 ), and serum tumor necrosis factor-α level (SMD = −8.45, 95% CI: [−11.20, −5.69], P < 0.001 ) of the ZQFTN treatment group were lower, and the total effective rate was higher relative risk (RR = 1.15, 95% CI [1.07, 1.23], P < 0.001 ). There was no significant difference in the incidence of adverse reactions between the two groups (RR = 0.96, 95% CI: [0.69, 1.35], P = 0.82 ). Conclusion. ZQFTN can effectively relieve knee pain, morning stiffness, and daily activity function disorders, reduce the expression of inflammatory factors in serum, and improve the total clinical response rate without increasing the incidence of adverse reactions. Therefore, ZQFTN has considerable potential as a CAM for KOA. However, due to the limitation of the quality of the included studies, the strength of this conclusion is affected. In the next step, multicenter, large sample, high-quality randomized controlled studies are needed to further confirm the present conclusion.
Objective: To examine the effect and mechanism of Strychnine total alkaloids on a model of knee osteoarthritis. Methods: New Zealand rabbits were randomly divided into normal group, model group, total alkaloid high/medium/low dose groups and a sodium hyaluronate group. Except for the normal control group, all other groups were injected with papain in the joint cavity to establish osteoarthritis. After 8 weeks of modeling, a high, medium and low dose of Strychnine total alkaline was given by injection in the joint cavity, 0.3 ml, 0.2 ml, and 0.1 ml respectively. At this time an intra-articular injection of 0.2 ml sodium hyaluronate was also given to the hyaluronate group. The injection of Strychnine total alkaline was continually administered, twice a week for 5 weeks. All animals were harvested for analysis one week after the final dose. Pathological changes of articular cartilage were observed and evaluated by Mankin's score. Total blood viscosity (low shear, middle shear, high shear) and plasma viscosity were measured by hemorheometer. The levels of IL-1 and IL-6, SOD, LPO, NO, and TNF in the synovial fluid and PYD in urine were additionally measured by enzyme-linked immunosorbent assay (ELISA). Main findings: Compared with the osteoarthritis controls, the cartilage injury was significantly improved in the total alkaloid group. Mankin's score was significantly decreased (P<0.05), and the blood viscosity and plasma viscosity of low, middle and high shear rates was decreased (P<0.05). Finally, IL-1, IL-6, LPO, NO and TNF in synovial fluid were decreased while SOD content increased (P<0.05). Conclusion: These results indicate that Strychnine total alkaloids have reparative effects on cartilage injury during osteoarthritis. The mechanisms may at least partially be related to the inhibition of inflammatory factors, the regulation of free radicals and the overall improvement of cartilage metabolism.
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