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Concurrent PIEZO1 activation and ATP2B4 blockade effectively reduce the risk of cerebral malaria and inhibit in vitro Plasmodium falciparum multiplication in red blood cells

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Genes & Diseases 2023年第6期10卷 2210-2214页

作者： Mathieu Adjemout Bruno Pouvelle Fatou Thiam Alassane Thiam Magali Torres Samia Nisar Babacar Mbengue Alioune Dieye Pascal Rihet Sandrine Marquet Institut National de la SantéEt de la Recherche Médicale(INSERM) UnitéMixte de Recherche(UMR)U1090Aix Marseille UniversitéTAGC Theories and Approaches of Genomic ComplexityInstitut MarMaRaMarseilleFrance Groupe de Recherche Biotechnologie Appliquée et Bioprocédés Environnementaux(GRBA-BE) Ecole Supérieure PolytechniqueUniversitéCheikh Anta Diop de DakarDakar BP5005Senegal Pole D’Immunophysiopathologie&Maladies Infectieuses(IMI) Institut Pasteur de DakarDakar BP 220Senegal Service D’Immunologie UniversitéCheikh Anta Diop de DakarDakar BP5005Senegal Aix Marseille University CNRSMarseille 13009France

Malaria caused by the Plasmodium falciparum parasite is responsible for more than 240 million cases per year and killed 627,000 people in 2020,mostly African children.The malaria parasite is transmitted by mosquitos belonging to the genus Anopheles.After an asymptomatic liver stage,the parasite is released into the bloodstream to invade red blood cells(RBCs)and replicate asexually.This erythrocytic phase is associated with a variety of clinical manifestations,including mild and severe malaria.Cerebral malaria(CM)is one of the most severe forms,characterized by the sequestration of parasitized RBCs in the small capillaries of the brain and the local development of cytokine-mediated inflammation.Genetic variants in genes encoding proteins involved in red blood cell physiology are protective factors against severe malaria,as clearly demonstrated for the sickle cell variant of hemoglobin(HbS).

关键词： malaria falciparum Plasmodium

Effects and Mechanism of Action of Artemisinin on Mitochondria of Plasmodium berghei

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Chinese Journal of Integrative Medicine 2020年第4期26卷 277-282页

作者： HOU Hong-ping ZHANG Guang-ping MA Li-na SU Ping ZHANG Zhong-xiu DAI Bao-qiang YE Zu-guang Institute of Chinese Materia Medica China Academy of Chinese Medical SciencesBeijing(100700)China

Objective:To study the antimalarial effects and mechanisms of artemisinin(Qinghaosu in Chinese,QHS)on mitochondria in mice infected with Plasmodium berghei.Methods:A total of 108 C57 mice infected with Plasmodium berghei were randomly divided into 3 groups by weight:the control group,200 and 400 mg/kg QHS groups.The two QHS treatment groups were further divided into 4 sub-groups with 12 animals each time according to the treatment time,0.5,1,2,and 4 h.Normal saline was intragastrically(i.g.)administered to the control group.The other two groups received different doses of QHS by i.***.administration.Animals were treated once with QHS for different detection time as follows:0.5,1,2,and 4 h.The mitochondrial energy metabolism,oxidative damage,membrane potential,and membrane permeability and other indexes were detected.Results:After administration of 200 and 400 mg/kg QHS,adenosine triphosphate(ATP)levels in Plasmodium and its mitochondria were reduced(PPlasmodium were the targets of QHS,which can adversely affect mitochondrial energy metabolism,oxidative damage,membrane potential,and membrane opening,and ultimately exert an antimalarial effect.

关键词： Qinghaosu Clinese medicine Plasmodium mitochondria antimalarial effect

Polyparasitism with Schistosoma haematobium,Plasmodium and soil-transmitted helminths in school-aged children in Muyuka-Camero on following implementation ofc ontrol measures:a cross sectional study

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Infectious Diseases of Poverty 2021年第1期10卷 100-101页

作者： Irene Ule Ngole Sumbele Ofon Vitalis Otia Orelien Sylvain Mtopi Bopda Calvin Bisong Ebai Helen KuoKuo Kimbi Theresa Nkuo-Aknjif Department of Zoology and Animal Physiology University of BueaBueaCameroon 不详

Background:Despite the ubiquity of polyparasitism,its health impacts have been inadequately studied.The aim of this study was to determine the prevalence and determinants of polyparasitism with Schistosoma haematobium,Plasmodium and soil-transmitted helminths(STH)following sustained control measures,as well as evaluate the outcomes and clinical correlates of infection in school-aged children(SAC)living in the schistosomiasis endemic focus of Muyuka-Cameroon.Methods:In a cross-sectional study,urine,blood and stool samples were each collected from SAC(4-14 years)selected at random between March and June 2015.Microhaematuria in urine was detected using reagent strip and 5.haematobium ova by filtration/microscopy methods.Plasmodium was detected using Giemsa-stained blood films and complete blood count was obtained using an auto-haematology analyser.STH in stool was detected by the Kato-Katz method.Categorical and continuous variables were compared as required,Kappa value estimated and the adjusted odds ratio(aOR)in the multivariate analysis was used to evaluate association of the risk factors with infection.

关键词： Polyparasitism School-age children Schistosoma haematobium Plasmodium Soil-transmitted helminths Morbidity Risk factor Cameroon

Comparative effects of parenteral antimalarials in Swiss albino mice after chronic exposure to Plasmodium berghei

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Animal Models and Experimental Medicine 2018年第3期1卷 235-241页

作者： Sylvester Aghahowa Kenka Okolocha Department of Pharmacology and Toxicology University of Benin

Mice are considered to be a similar model to humans in the pathogenesis of malaria. This study evaluates the effect of parenteral antimalarials on the spleen and liver of Swiss albino mice after chronic exposure to Plasmodium berghei. After chronic exposure to P. berghei NK65 strain, the level of parasitemia was assessed.The mice were treated for 3 days using chloroquine(5 mg/kg), quinine(10 mg/kg),and artemether(2 mg/kg). The effect of chronic exposure and the pattern of recovery were evaluated. There was significant decrease in total body weight after chronic exposure to P. berghei(P < 0.05). An increase in total weight recovery was seen after day 15 of treatment with the antimalarials; this was more pronounced with artemether. A significant increase in liver and spleen weights due to P. berghei infection was seen. There was a recovery pattern due to decrease in liver and spleen weights following antimalarial administration, which was greatest with artemether(P < 0.05). Significant changes were more in parasitized, quinine and artemether groups(P < 0.05). There was a significant decrease in total spleen protein due to chloroquine but a decrease due to quinine and artemether(P < 0.05). No significant changes in liver and spleen albumin were observed after treatment. The highest parasite clearance was observed with artemether, followed by quinine. Five mice died after chronic exposure in all the groups prior to treatment. There was significant enlargement and discoloration of spleen and liver after chronic exposure. This study showed that artemether aided recovery of the liver and spleen better than quinine and chloroquine in albino mice after chronic exposure to P. berghei. This suggests there is potential for improvement in antimalarial therapy.

关键词： antimalarials mice Plasmodium berghei

Prevalence of and risk factors for severe malaria caused by Plasmodium and dengue virus co-infection: a systematic review and meta-analysis

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Infectious Diseases of Poverty 2020年第5期9卷 120-121页

作者： Manas Kotepui Kwuntida Uthaisar Kotepui Giovanni De Jesus Milanez Frederick Ramirez Masangkay Medical Technology School of Allied Health SciencesWalailak UniversityTha SalaNakhon Si ThammaratThailand 不详

Background:Co-infection with both Plasmodium and dengue virus(DENV)infectious species could have serious and fatal outcomes if left undiagnosed and without timely treatment.The present study aimed to determine the pooled prevalence estimate of severe malaria among patients with co-infection,the risk of severe diseases due to co-infection,and to describe the complications of severe malaria and severe dengue among patients with coinfection.Methods:Relevant studies published between databases between 12 September 1970 and 22 May 2020 were identified and retrieved through a search of the ISI Web of Science,Scopus,and MEDLINE.The pooled prevalence and 95%confidence interval(CI)of severe malaria among patients with Plasmodium and DENV co-infection was estimated with a random-effects model to take into account the between-study heterogeneity of the included studies.The risks of severe malaria and severe diseases due to co-infection were estimated with the pooled odds ratio(OR)and 95%CI with a random-effects model.Results:Of the 5653 articles screened,13 studies were included in the systematic review and meta-analysis.The results demonstrated that the pooled prevalence estimate of severe malaria among patients with co-infection was 32%(95%CI:18-47%,I 2=92.3%).Patients with co-infection had a higher risk of severe diseases than those with DENV mono-infection(odds ratio[OR]=3.94,95%CI:1.96-7.95,I 2=72%).Patients with co-infection had a higher risk of severe dengue than those with DENV mono-infection(OR=1.98,95%CI:1.08-3.63,I 2=69%).The most severe complications found in severe dengue were bleeding(39.6%),jaundice(19.8%),and shock/hypotension(17.9%),while the most severe complications found in severe malaria were severe bleeding/bleeding(47.9%),jaundice(32.2%),and impaired consciousness(7.43%).Conclusions:The present study found that there was a high prevalence of severe malaria among patients with Plasmodium and DENV co-infection.Physicians in endemic areas where these two diseases overlap should recognize that patients wi

关键词： Plasmodium Malaria Dengue Severe complications Severity

Immunogenicity and immunizing protection effect of GAMA gene DNA vaccine on Plasmodium berghei

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Asian Pacific Journal of Tropical Medicine 2016年第2期9卷 154-159页

作者： Feng Du Si Wang Chen Zhao Ya-Ming Cao En-Jie Luo Department of Pathogen Biology Basic Medical College of China Medical University Inspection Institute of Jilin Medical College Department of Immunology Basic Medical College of China Medical University

Objective: To explore the effect of immunogenicity and immunizing protection of GAMA gene DNA vaccine, which was related with merozoite, ookinete and sporozoite invasion. Methods:Gene fragments were obtained using PCR technique and eukaryotic expression vector(containing immunostimulatory sequence) was built. BALB/c mice were divided into PBS control group, empty vector control group and study group and were immunized at week 0, 3 and 6 respectively. Blood was collected 2 weeks after each immunization and serum was separated to detect the Ig G, Ig G1 and Ig G2 a levels. Spleen of mice was obtained for preparation of splenic mononuclear cell and the cytokine IL-4 and IFN-αlevels were detected. Indirect immunofluorescence and western blot were employed to verify the specificity of antiserum. Sporozoite and merozoite invasion were used respectively to detect the immune protective effect 2 weeks after the third immunization. Ookinete conversion rate in vitro and oocyst numbers of mosquito stomach were observed to evaluate the transmission-blocking levels. Results: In GAMA DNA vaccine group: antiserum could be combined with recombinant protein specifically and green fluorescence signals of merozoite, ookinete and sporozoite were observable, while specific fragments and fluorescence signals were not observable in empty vector group. Compared with control group, specific Ig G in DNA vaccine immunity group significantly increased(P<0.01), and Ig G1 and Ig G2 a all increased(P<0.01). IL-4, IFN-αcontent in study group significantly increased, compared with control group(P<0.01). GAMA DNA vaccine immunity could not obviously block the erythrocyte-stage infection(caused by sporozoite invasion); compared with control group, liver worm load was slightly reduced(P<0.05), and antiserum ookinete numbers(cultured in vitro) had no significant difference with oocyst numbers of mosquito stomach in DNA vaccine group. Conclusions:GAMA has good antigenicity, which could stimulate the body to produce specific immune responses; while DNA

关键词： Malaria vaccine DNA vaccine Multi-stage vaccine GAMA Plasmodium berghei

Andrographolide effect on both Plasmodium falciparum infected and noninfected RBCs membranes

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Asian Pacific Journal of Tropical Medicine 2015年第7期8卷 505-510页

作者： Zaid O Ibraheem Abd Majid R Sabariah MN Hasidah MS Al-Zihiry K Yam MF Basir R Pharmacology Unit Department of Human Anatomy Faculty of Medicine and Health Sciences Universiti Putra Malaysia Department of Medical Microbiology and Parasitology Faculty of Medicine and Health Sciences Universiti Putra Malaysia Department of Hematology Faculty of Medicine and Health Sciences Universiti Putra Malaysia School of Bioscience and Biotechnology Faculty of Science and Technology Universiti Kebangsaan Malaysia School of pharmaceutical science Universiti Sains Malaysia

Objective: To explore whether its antiPlasmodium effect of andrographolide is attributed to its plausible effect on the plasma membrane of both Plasmodium falciparum infected and noninfected RBCs. Methods: Anti-Plasmodium effect of andrographolide against Plasmodium falciparum strains was screened using the conventional malaria drug sensitivity assay. The drug was incubated with uninfected RBCs to monitor its effect on their morphology, integrity and osmotic fragility. It was incubated with the Plasmodium infected RBCs to monitor its effect on the parasite induced permeation pathways. Its effect on the potential of merozoites to invade new RBCs was tested using merozoite invasion assay. Results: It showed that at andrographolide was innocuous to RBCs at concentrations approach its therapeutic level against plasmodia. Nevertheless, this inertness was dwindled at higher concentrations. Conclusions: In spite of its success to inhibit Plasmodium induced permeation pathway and the potential of merozoites to invade new RBCs, its anti-Plasmodium effect can't be attributed to these functions as they were attained at concentrations higher than what is required to eradicate the parasite. Consequently, other mechanisms may be associated with its claimed actions.

关键词： Andrographolide Terpenoid Plasmodium falciparum Merozoites Permeation & Osmotic fragility

Nano chloroquine delivery against Plasmodium berghei NK65 induced programmed cell death in spleen

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Asian Pacific Journal of Tropical Medicine 2018年第9期11卷 540-546页

作者： Satyajit Tripathy Sourav Chattopadhyay Sandeep Kr.Dash Motlalepula G.Matsabisa Somenath Roy Immunology and Microbiology Laboratory Department of Human Physiology with Community HealthVidyasagar University Department of Pharmacology University of the Free State B.S.B.E.Indian Institute of Technology University of Gour Banga

Objective:To compare the protective effects of chitosan-trypolyphosphate(CS-TPP) nanoparticle conjugated chloroquine(CQ) with effect of CQ alone on the reversal of splenic damages and induction of apoptosis.Methods:Different researches have been carried out to explore the potential role of chitosan based drug delivery system against parasitic diseases.After successive Plasmodium berghei NK65 parasiste infection by intraperitoneal injection in Swiss mice and subsequent parasite development,the ROS generation,anti-apoptotic and pro apoptotic protein levels in spleen were measured.To analyze caspases,flow cytometry study was performed with annexin 桋-FITC and with PI staining.Results:The results revealed that ROS mediated caspase 3 and 9 activation and the induction of apoptosis occurred during the parasitic infection.However,CS-TPP conjugated CQ was relatively better in reversing the splenic damage compared with similar effects of CQ alone.Conclusions:This study indicates that Plasmodium berghei NK65 induces apoptosis in the spleen.The study further shows that CS-TPP nanoparticles conjugation with CQ have positive influence on the recovery of damaged host's system towards maintenance of normal homeostasis,and this is shown to be selective to CS-TPP conjugated CQ treated animals only.

关键词： Splenocyte Apoptosis Nano chloroquine Plasmodium berghei Chitosan

Antimalarial potential of kolaviron,a biflavonoid from Garcinia kola seeds,against Plasmodium berghei infection in Swiss albino mice

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Asian Pacific Journal of Tropical Medicine 2014年第2期7卷 97-104页

作者： Adaramoyc Oluwatosin Akinpelu Tolulope Kosoko Ayokulchin Okoric Patricia Kehinde Aderemi Falade Catherine Ademowo Olusegun Biochemistry Department University of IbadanUniversity wayOyo-OjooRoadIbadanIbadan.Oyo/South-West 20005Nigeria Pharmacology Department University of IbadanUniversity way.Oyo-OjooRoadIbadanIbadanOyo/South-West 20005Nigeria Medical Microbiology Department.University of Ibadan University wayOyo-OjooRoadIbadanIbadanOyo/South-West 20005Nigeria Pharmacology and IAMRAT Department.University of Ibadan University wayOyo-OjooRoad.IbadanIbadanOyo/South-West 20005.Nigeria

Objective:To investigate the antimalarial potential of kolaviron(KV),a biflavonoid fraction from Garcinia kola seeds,against Plasmodium berghei(P.berghei)infection in Swiss albino mice.Methods:The study consists of seven groups of ten mice each.Groups I,II and III were normal mice that received com oil.KV1 and chloroquine(CQ),respectively.Groups IV,V,ⅥandⅦwere infected mice that received corn oil.CQ,KYI and KV2.respectively.CQ.KY1 and KV2were given at 10-,100-and 200-mg/kg daily,respectively for three consecutive days.Results:Administration of KV1 and KV2 significantly(P<0.05)suppressed P.berghei-infection in the mice by 85%and 90%.respectively,while CQ produced 87%suppression relative to untreated infected group after the fifth day of treatment.Also,KV2 significantly(P<0.05)increased the mean survival time of the infected mice by 175%.The biflavonoid prevented a drastic reduction in HCV from day4 of treatment,indicating its efficacy in ameliorating anaemia.Significant(P<0.05)oxidative stress assessed by the elevation of serum and hepatic malondialdehydewere observed in unlrealed P.berghei-infected mice.Specifically,senum and hepatic malondialdehyde levels increased by93%and 78%,resjiectively in the unlrealed infecled mice.Furlhennore,antioxidant indices,viz;superoxide dismutase.catalase,glutathione-s-transferasc.glualhione peroxidase and reduced gluathione decreased significantly(P<0.05)in the tissues of untreated P.berghei-infected mice.KV significantly(P<0.05)ameliorated the P.berghei-induced decrease in antioxidant status of the infected mice.Conclusions:This study shows that kolaviron,especially at 200 mg/kg,has high antimalarial activities in P.berghei-infected mice,in addition to its known antioxidant properties.

关键词： Antimalaria Antioxidant Biflavonoid Kolaviron Plasmodium berghei