Browse
Submit Data
Databases
API
Help

Dataset Information

9 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Establishment and evaluation of glucose-modified nanocomposite liposomes for the treatment of cerebral malaria.

ABSTRACT: Cerebral malaria (CM) is a life-threatening neurological complication caused by Plasmodium falciparum. About 627,000 patients died of malaria in 2020. Currently, artemisinin and its derivatives are the front-line drugs used for the treatment of cerebral malaria. However, they cannot target the brain, which decreases their effectiveness. Therefore, increasing their ability to target the brain by the nano-delivery system with brain-targeted materials is of great significance for enhancing the effects of antimalarials and reducing CM mortality. This study used glucose transporter 1 (GLUT1) on the blood-brain barrier as a target for a synthesized cholesterol-undecanoic acid-glucose conjugate. The molecular dynamics simulation found that the structural fragment of glucose in the conjugate faced the outside the phospholipid bilayers, which was conducive to the recognition of brain-targeted liposomes by GLUT1. The fluorescence intensity of the brain-targeted liposomes (na-ATS/TMP@lipoBX) in the mouse brain was significantly higher than that of the non-targeted liposomes (na-ATS/TMP@lipo) in vivo (P < 0.001) after intranasal administration. The infection and recurrence rate of the mice receiving na-ATS/TMP@lipoBX treatment were significantly decreased, which had more advantages than those of other administration groups. The analysis of pharmacokinetic data showed that na-ATS/TMP@lipoBX could enter the brain in both systemic circulation and nasal-brain pathway to treat malaria. Taken together, these results in this study provide a new approach to the treatment of cerebral malaria.

SUBMITTER: Tian Y

PROVIDER: S-EPMC9258070 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Indocyanine Green Liposomes for Diagnosis and Therapeutic Monitoring of Cerebral Malaria.

Project description:Cerebral malaria (CM) is a major cause of death of Plasmodium falciparum infection. Misdiagnosis of CM often leads to treatment delay and mortality. Conventional brain imaging technologies are rarely applicable in endemic areas. Here we address the unmet need for a simple, non-invasive imaging methodology for early diagnosis of CM. This study presents the diagnostic and therapeutic monitoring using liposomes containing the FDA-approved fluorescent dye indocyanine green (ICG) in a CM murine model. Increased emission intensity of liposomal ICG was demonstrated in comparison with free ICG. The Liposomal ICG's emission was greater in the brains of the infected mice compared to naïve mice and drug treated mice (where CM was prevented). Histological analyses suggest that the accumulation of liposomal ICG in the cerebral vasculature is due to extensive uptake mediated by activated phagocytes. Overall, liposomal ICG offers a valuable diagnostic tool and a biomarker for effectiveness of CM treatment, as well as other diseases that involve inflammation and blood vessel occlusion.

| S-EPMC4729766 | biostudies-literature

Glucose metabolism mediates disease tolerance in cerebral malaria.

Project description:Sickness behaviors are a conserved set of stereotypic responses to inflammatory diseases. We recently demonstrated that interfering with inflammation-induced anorexia led to metabolic changes that had profound effects on survival of acute inflammatory conditions. We found that different inflammatory states needed to be coordinated with corresponding metabolic programs to actuate tissue-protective mechanisms. Survival of viral inflammation required intact glucose utilization pathways, whereas survival of bacterial inflammation required alternative fuel substrates and ketogenic programs. We thus hypothesized that organismal metabolism would be important in other classes of infectious inflammation and sought to understand its role in the prototypic parasitic disease malaria. Utilizing the cerebral malaria model, Plasmodium berghei ANKA (PbA) infection in C57BL/6J male mice, we unexpectedly found that inhibition of glycolysis using 2-deoxy glucose (2DG) conferred protection from cerebral malaria. Unlike vehicle-treated animals, 2DG-treated animals did not develop cerebral malaria and survived until ultimately succumbing to fatal anemia. We did not find any differences in parasitemia or pathogen load in affected tissues. There were no differences in the kinetics of anemia. We also did not detect differences in immune infiltration in the brain or in blood-brain barrier permeability. Rather, on pathological analyses performed on the entire brain, we found that 2DG prevented the formation of thrombi and thrombotic complications. Using thromboelastography (TEG), we found that 2DG-treated animals formed clots that were significantly less strong and stable. Together, these data suggest that glucose metabolism is involved in inflammation-induced hemostasis and provide a potential therapeutic target in treatment of cerebral malaria.

| S-EPMC6205430 | biostudies-literature

Bauhinia purprea agglutinin-modified liposomes for human prostate cancer treatment.

Project description:Bauhinia purprea agglutinin (BPA) is a well-known lectin that recognizes galactosyl glycoproteins and glycolipids. In the present study, we firstly found that BPA bound to human prostate cancer specimens but not to normal prostate ones. Therefore, we sought to develop BPA-PEG-modified liposomes (BPA-PEG-LP) encapsulating anticancer drugs for the treatment of prostate cancer. We examined the tumor targetability of BPA-PEG-LP with human prostate cancer DU145 cells, and observed that fluorescently labeled BPA-PEG-LP dominantly associated with the cells via the interaction between liposome-surface BPA and cell-surface galactosyl molecules. We also observed that BPA-PEG-LP accumulated in the prostate cancer tissue after the i.v. injection to DU145 solid cancer-bearing mice, and strongly bound to the cancer cells. In a therapeutic study, DU145 solid cancer-bearing mice were i.v. injected thrice with BPA-PEG-LP encapsulating doxorubicin (BPA-PEG-LPDOX, 2 mg/kg/day as the DOX dosage) or PEG-modified liposomes encapsulating DOX (PEG-LPDOX). As a result, BPA-PEG-LPDOX significantly suppressed the growth of the DU145 cancer cells, whereas PEG-LPDOX at the same dosage as DOX showed little anti-cancer effect. The present study suggested that BPA-PEG-LP could be a useful drug carrier for the treatment of human prostate cancers.

| S-EPMC4724813 | biostudies-literature

Cerebral malaria versus asymptomatic malaria

Project description:We hypothesized that differential gene expression contributes to phenotypic variation of parasites which results in specific interaction of Plasmodium falciparum with its human host. In this study we used microarray hybridization to analyse the transcriptomes of P.falciparum isolated from asymptomatic carriers and from cerebral and uncomplicated malaria patients. We also investigated the transcriptomes of the 3D7 clone and the selected 3D7-Lib line.

2014-12-01 | E-MTAB-2139 | biostudies-arrayexpress

LPS adsorption and inflammation alleviation by polymyxin B-modified liposomes for atherosclerosis treatment

Project description: Not available

| S-EPMC10501887 | biostudies-literature

Treatment Reducing Endothelial Activation Protects against Experimental Cerebral Malaria.

Project description:Cerebral malaria (CM) is the most severe neurological complication of malaria caused by Plasmodium falciparum infection. The available antimalarial drugs are effective at clearing the parasite, but the mortality rate remains as high as 20% of CM cases. At the vascular level, CM is characterized by endothelial activation and dysfunction. Several biomarkers of endothelial activation have been associated with CM severity and mortality, making the brain vascular endothelium a potential target for adjunctive therapies. Statins and Angiotensin II Receptor Blockers (ARBs) are drugs used to treat hypercholesterolemia and hypertension, respectively, that have shown endothelial protective activity in other diseases. Here, we used a combination of a statin (atorvastatin) and an ARB (irbesartan) as adjunctive therapy to conventional antimalarial drugs in a mouse experimental model of CM. We observed that administration of atorvastatin-irbesartan combination decreased the levels of biomarkers of endothelial activation, such as the von Willebrand factor and angiopoietin-1. After mice developed neurological signs of CM, treatment with the combination plus conventional antimalarial drugs increased survival rates of animals 3-4 times compared to treatment with antimalarial drugs alone, with animals presenting lower numbers and smaller hemorrhages in the brain. Taken together, our results support the hypothesis that inhibiting endothelial activation would greatly reduce the CM-associated pathology and mortality.

| S-EPMC9229727 | biostudies-literature

Photocatalytic study of nanocomposite membrane modified by CeF3 catalyst for pharmaceutical wastewater treatment.

Project description:Cerium fluoride (CeF3) nanoparticles (NPs) were synthesized and applied in polysulfone (PS) membrane fabricated by phase inversion method. The produced nanocomposite membranes (PS/CeF3) with different contents of CeF3 NPS (0.25%, 0.5%, 0.75% and 1% w/w) were used to treat pharmaceutical wastewaters. The membranes were characterized by FESEM, EDX, XRD, FTIR, porosity, and water contact angle analyses. Evaluation of the characteristics and performance of the nanocomposite membranes confirmed that utilizing photocatalytic CeF3 NPs in membrane structure could effectively decompose organic contaminants in pharmaceutical wastewaters. It also improves the hydrophilicity and antifouling ability of membrane during filtration especially, in the presence of UV irradiation. The permeate flux of the PS membrane increased from 35.1 to 63.77 l/m2h by embedding 0.75% of CeF3 NPs in membrane structure due to the porosity enhancement from 71.36-78.42% and the decrease in contact angle from 62.9º to 53.73º. Moreover, the flux decline of PS/CeF3-0.75% membrane under UV irradiation was from 63.6 to 46.1 l/m2h that considerably lower than that of the neat PS membrane (from 34.7 to 4.9). On the other hand, the degradation efficiency of PS/CeF3-0.75% membrane was more than 97%, and COD removed was more than 65% while they were 75% and 31%, respectively for the nascent PS membrane. Therefore, applying the appropriate amount of CeF3 NPs in PS membranes not only greatly increased the permeate flux but also significantly enhanced the degradation efficiency and COD removal. This indicates that nanocomposite membranes can be confidently applied for pharmaceutical wastewater treatment UV irradiation.

| S-EPMC7721854 | biostudies-literature

Murine cerebral malaria: how far from human cerebral malaria?

Project description: Not available

| S-EPMC2883649 | biostudies-literature

Evaluation of Nanocomposite Made of Polylactic Acid and Nanocellulose from Carrot Pomace Modified with Silver Nanoparticles.

Project description:In this research, it was proposed to use carrot cellulose nanofibrils (CCNF) isolated from carrot pomace modified with silver nanoparticles (AgNPs) as a filler of polylactic acid (PLA) composites matrix. The new procedure was based on two steps: first, the preparation of nanocellulose modified with metal nanoparticles, and then the combination with PLA. Two concentrations-0.25 mM and 2 mM-of AgNO3 were used to modify CCNF. Then, PLA was mixed with the filler (CCNF/AgNPs) in two proportions 99:1 and 96:4. The influence of CCNF/AgNPs on mechanical, hydrophilic, thermal, and antibacterial properties of obtained nanocomposites was evaluated. The greatest improvement of mechanical properties was observed for composite containing CCNF with 2 mM of AgNPs, which obtained the lowest Young modulus and highest strain at break. The degradation temperature was lower for PLA with CCNF/AgNPs, but crystallization temperature wasn't influenced. The addition of CCNF/AgNPs also increased hydrophilicity. The transmission rates of oxygen, nitrogen, and carbon dioxide also increased after the addition of CCNF/AgNPs to PLA. The antibacterial function against Escherichia coli and Bacillus cereus was obtained after the addition of AgNPs but only at the contact surface with the material made, suggesting the lack of migration of nanoparticles from the composite.

| S-EPMC7240409 | biostudies-literature

Pediatric Cerebral Malaria.

Project description: Not available

| S-EPMC8210844 | biostudies-literature