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Albendazole is the drug of choice for the treatment of echinococcosis, but it is difficult to meet clinical goals with this chemotherapy due to its low cure rate and associated side effects after its long-term use. Hence, novel anti-parasitic targets and effective treatment alternatives are urgently needed. A previous study showed that verapamil (Vepm) can suppress the growth of\n                      <jats:italic>Echinococcus granulosus<\/jats:italic>\n                      larvae; however, the mechanism of this effect remains unclear. The aim of the present study was to gain insight into the anti-echinococcal effect of Vepm on\n                      <jats:italic>Echinococcus<\/jats:italic>\n                      with a particular focus on the regulatory effect of Vepm on calcium\/calmodulin-dependent protein kinase II (Ca\n                      <jats:sup>2+<\/jats:sup>\n                      \/CaM-CaMKII) in infected mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The anti-echinococcal effects of Vepm on\n                      <jats:italic>Echinococcus granulosus<\/jats:italic>\n                      protoscoleces (PSC)\n                      <jats:italic>in vitro<\/jats:italic>\n                      and\n                      <jats:italic>Echinococcus multilocularis<\/jats:italic>\n                      metacestodes in infected mice were assessed. The morphological alterations in\n                      <jats:italic>Echinococcus<\/jats:italic>\n                      spp. induced by Vepm were observed by scanning electron microscopy (SEM), and the changes in calcium content in both the parasite and mouse serum and liver were measured by SEM-energy dispersive spectrometry, inductively coupled plasma mass spectrometry and alizarin red staining. Additionally, the changes in the protein and mRNA levels of CaM and CaMKII in infected mice, and in the mRNA levels of\n                      <jats:italic>CaMKII<\/jats:italic>\n                      in\n                      <jats:italic>E. granulosus<\/jats:italic>\n                      PSC, were evaluated after treatment with Vepm by immunohistochemistry and\/or real-time quantitative polymerase chain reaction.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>In vitro<\/jats:italic>\n                      ,\n                      <jats:italic>E. granulosus<\/jats:italic>\n                      PSC could be killed by Vepm at a concentration of 0.5 \u03bcg\/ml or higher within 8 days. Under these conditions, the ultrastructure of PSC was damaged, and this damage was accompanied by obvious calcium loss and downregulation of\n                      <jats:italic>CaMKII<\/jats:italic>\n                      mRNA expression.\n                      <jats:italic>In vivo<\/jats:italic>\n                      , the weight and the calcium content of\n                      <jats:italic>E. multilocularis<\/jats:italic>\n                      metacestodes from mice were reduced after treatment with 40 mg\/kg Vepm, and an elevation of the calcium content in the sera and livers of infected mice was observed. In addition, downregulation of CaM and CaMKII protein and mRNA expression in the livers of mice infected with\n                      <jats:italic>E. multilocularis<\/jats:italic>\n                      metacestodes was found after treatment with Vepm.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Vepm exerted a parasiticidal effect against\n                      <jats:italic>Echinococcus<\/jats:italic>\n                      both\n                      <jats:italic>in vitro<\/jats:italic>\n                      and\n                      <jats:italic>in vivo<\/jats:italic>\n                      through downregulating the expression of Ca\n                      <jats:sup>2+<\/jats:sup>\n                      \/CaM-CaMKII, which was over-activated by parasitic infection. The results suggest that Ca\n                      <jats:sup>2+<\/jats:sup>\n                      \/CaM-CaMKII may be a novel drug target, and that Vepm is a potential anti-echinococcal drug for the future control of echinococcosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical Abstract<\/jats:title>\n                  <\/jats:sec>","DOI":"10.1186\/s13071-021-04618-4","type":"journal-article","created":{"date-parts":[[2021,2,17]],"date-time":"2021-02-17T09:25:19Z","timestamp":1613553919000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Anti-echinococcal effect of verapamil involving the regulation of the calcium\/calmodulin-dependent protein kinase II response in vitro and in a murine infection model"],"prefix":"10.1186","volume":"14","author":[{"given":"Hai-Jun","family":"Gao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu-Dong","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan-Ping","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua-Sheng","family":"Pang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing-Ming","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Jing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Juan","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-Ping","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,2,15]]},"reference":[{"key":"4618_CR1","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1186\/s13071-016-1687-y","volume":"9","author":"H Wang","year":"2016","unstructured":"Wang H, Li J, Guo B, Zhao L, Zhang Z, McManus DP, et al. 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