- Low-dose intravenous and subcutaneous CIS43LS monoclonal antibody for protection against malaria (VRC 612 Part C): a phase 1, adaptive trial. [Journal Article]Lancet Infect Dis. 2023 Jan 25 [Online ahead of print]LI
- CONCLUSIONS: CIS43LS was safe and well tolerated, and conferred protection against P falciparum at low doses and by the subcutaneous route, providing evidence that this approach might be useful to prevent malaria across several clinical use cases.
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- High-Throughput Quantitative Glycomics Enabled by 12-plex Isobaric Multiplex Labeling Reagents for Carbonyl-Containing Compound (SUGAR) Tags. [Journal Article]J Proteome Res. 2023 Jan 26 [Online ahead of print]JP
- Glycans, which are widely distributed on most proteins and cell surfaces, are a class of important biomolecules playing crucial roles in various biological processes such as immune response and cellular communication. Modern mass spectrometry (MS) coupled with novel chemical probes greatly facilitates routine analysis of glycans. However, the requirement of high-throughput analysis still calls fo…
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- A High-Throughput Amenable Dual Luciferase System for Measuring Toxoplasma gondii Bradyzoite Viability after Drug Treatment. [Journal Article]
- It is estimated that more than 2 billion people are chronically infected with the intracellular protozoan parasite Toxoplasma gondii (T. gondii). Despite this, there is currently no vaccine to prevent infection in humans, and there is no recognized curative treatment to clear tissue cysts. A major hurdle for identifying effective drug candidates against chronic-stage cysts has been the low throug…
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- Timing of hypoxia PET/CT imaging after 18F-fluoromisonidazole injection in non-small cell lung cancer patients. [Journal Article]
- Positron emission tomography (PET)/computed tomography (CT) using the radiotracer 18F-Fluoromisonidazole (FMISO) has been widely employed to image tumour hypoxia and is of interest to help develop novel hypoxia modifiers and guide radiation treatment planning. Yet, the optimal post-injection (p.i.) timing of hypoxic imaging remains questionable. Therefore, we investigated the correlation between …
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- On the potential for discontinuing atovaquone-proguanil (AP) ad-hoc post-exposure and other abbreviated AP-regimens: Pharmacology, pharmacokinetics and perspectives. [Journal Article]Travel Med Infect Dis. 2022 Dec 14; 52:102520.TM
- According to current guidelines, atovaquone-proguanil (AP) malaria chemoprophylaxis should be taken once daily starting one day before travel and continued for seven days post-exposure. However, drug-sparing regimens, including discontinuing AP after leaving malaria-endemic areas are cost-saving and probably more attractive to travelers, and may thus enhance adherence. AP has causal prophylactic …
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- Single-Chain Polymer Nanoparticles Targeting the Ookinete Stage of Malaria Parasites. [Journal Article]
- Malaria is an infectious disease transmitted by mosquitos, whose control is hampered by drug resistance evolution in the causing agent, protist parasites of the genus Plasmodium, as well as by the resistance of the mosquito to insecticides. New approaches to fight this disease are, therefore, needed. Research into targeted drug delivery is expanding as this strategy increases treatment efficacies…
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- Unveiling the membrane bound dihydroorotate: Quinone oxidoreductase from Staphylococcus aureus. [Journal Article]Biochim Biophys Acta Bioenerg. 2022 Dec 06; 1864(2):148948.BB
- Staphylococcus aureus is an opportunistic pathogen and one of the most frequent causes for community acquired and nosocomial bacterial infections. Even so, its energy metabolism is still under explored and its respiratory enzymes have been vastly overlooked. In this work, we unveil the dihydroorotate:quinone oxidoreductase (DHOQO) from S. aureus, the first example of a DHOQO from a Gram-positive …
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- [Cell Cycle Arrest and Apoptosis Induced by Atovaquone in Non-Hodgkin's Lymphoma Raji Cells]. [Journal Article]Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2022 Dec; 30(6):1746-1751.ZS
- CONCLUSIONS: Atovaquone effectively inhibits cell proliferation and induces cell cycle arrest and apoptosis by suppression of STAT3 signaling pathway in Raji cells. It can be a potential therapeutic agent against non-Hodgkin's lymphoma.
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- Potential effects of alpha-pinene, a monoterpene commonly found in essential oils against Toxoplasma gondii infection; an in vitro and in vivo study. [Journal Article]
- This survey designed to assess the in vitro and in vivo activity of α-pinene, a monoterpene commonly originated in essential oils on Toxoplasma gondii. The in vitro effect of various concentration of α-pinene against tachyzoites of T. gondii Rh strain was assessed by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The activity of α-pinene on the stimulation of apoptosis …
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- Phosphatidylinositol 4-kinase is a viable target for the radical cure of Babesia microti infection in immunocompromised hosts. [Journal Article]
- Human babesiosis is a global emerging tick-borne disease caused by infection with intra-erythrocytic parasites of the genus Babesia. With the rise in human babesiosis cases, the discovery and development of new anti-Babesia drugs are essential. Phosphatidylinositol 4-kinase (PI4K) is a widely present eukaryotic enzyme that phosphorylates lipids to regulate intracellular signaling and trafficking.…
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- Data on the combined effect of atovaquone, mefloquine, and 3-bromopyruvic acid against Echinococcus multilocularis protoscoleces. [Journal Article]
- The dataset presented here is related to a previous research article titled "Mitochondrial Complex III in Larval Stage of Echinococcus multilocularis as a Potential Chemotherapeutic Target and in vivo Efficacy of Atovaquone Against Primary Hydatid Cysts"[1]. In this report, data were collected from aerobic and anaerobic culture assays of E. multilocularis protoscoleces in the presence of three an…
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- A pharmacokinetic-pharmacodynamic model for chemoprotective agents against malaria. [Journal Article]
- Chemoprophylactics are a vital tool in the fight against malaria. They can be used to protect populations at risk, such as children younger than the age of 5 in areas of seasonal malaria transmission or pregnant women. Currently approved chemoprophylactics all present challenges. There are either concerns about unacceptable adverse effects such as neuropsychiatric sequalae (mefloquine), risks of …
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- Validation of atovaquone plasma levels by liquid chromatography-tandem mass spectrometry for therapeutic drug monitoring in pediatric patients. [Journal Article]
- CONCLUSIONS: Our studies have shown that our LC-MS/MS-based method is both reliable and robust for the quantification of plasma atovaquone concentrations and can be used to determine the effective dose of atovaquone for pediatric patients treated for AML.
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- Proguanil and atovaquone use is associated with lower colorectal cancer risk: a nationwide cohort study. [Journal Article]
- CONCLUSIONS: This national-wide population-based cohort study showed that the use of proguanil and atovaquone was associated with a reduced risk of CRC among individuals with a family history of CRC.
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- Dual-activity nanozyme to initiate tandem catalysis for doubly enhancing ATP-depletion anti-tumor therapy. [Journal Article]Biomater Adv. 2022 Dec; 143:213181.BA
- Nanozymes can regulate metabolism to achieve precise anti-tumor therapy. However, the application of nanozymes with single catalytic properties is limited by complex tumor microenvironment (TME). Herein, we report a rarely discovered nanozyme ruthenium (Ru), which has double catalytic activity of glucose-oxidase-like (GOx-like) activity and peroxidase-like (POD-like) activity. Importantly, the GO…
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- Atovaquone-induced thrombocytopenia: A case report. [Journal Article]Int J Clin Pharmacol Ther. 2022 Nov 04 [Online ahead of print]IJ
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- Rare Case of Persistently Depressed T Lymphocyte Subsets After SARS-CoV-2 Infection. [Case Reports]
- BACKGROUND On rare occasions, viral infections are known to also depress immune cell lines, further worsening clinical outcomes. We describe a patient who presented 3 weeks after recovery from mild COVID-19 disease with clinical features of an atypical pneumonia and was found to have a low CD4+ T-cell count. CASE REPORT An 82-year-old man with a past medical history of coronary artery disease, rh…
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- Atovaquone attenuates experimental colitis by reducing neutrophil infiltration of colonic mucosa. [Journal Article]
- Ulcerative colitis (UC) is a chronic relapsing disease featuring aberrant accumulation of neutrophils in colonic mucosa and the luminal space. Although significant advances in UC therapy have been made with the development of novel biologics and small molecules targeting immune responses, success of most current therapies is still limited, with significant safety concerns. Thus, there is a need t…
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- Nanoengineering a Zeolitic Imidazolate Framework-8 Capable of Manipulating Energy Metabolism against Cancer Chemo-Phototherapy Resistance. [Journal Article]
- Chemo-phototherapy has emerged as a promising approach to complement traditional cancer treatment and enhance therapeutic effects. However, it still faces the challenges of drug efflux transporter-mediated chemoresistance and heat shock proteins (HSPs)-mediated phototherapy tolerance, which both depend on an excessive supply of adenosine triphosphate. Therefore, manipulating energy metabolism to …
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- Atovaquone for treatment of COVID-19: A prospective randomized, double-blind, placebo-controlled clinical trial. [Journal Article]
- Background: An in silico screen was performed to identify FDA approved drugs that inhibit SARS-CoV-2 main protease (Mpro), followed by in vitro viral replication assays, and in vivo pharmacokinetic studies in mice. These studies identified atovaquone as a promising candidate for inhibiting viral replication. Methods: A 2-center, randomized, double-blind, placebo-controlled trial was performed amo…
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- The Therapeutic Potential of Imidazole or Quinone-Based Compounds as Radiosensitisers in Combination with Radiotherapy for the Treatment of Head and Neck Squamous Cell Carcinoma. [Review]
- The addition of platinum chemotherapy to primary radiotherapy (chemoradiation) improves survival outcomes for patients with head and neck squamous cell carcinoma (HNSCC), but it carries a high incidence of acute and long-term treatment-related complications, resulting in a poor quality of life. In addition, patients with significant co-morbidities, or older patients, cannot tolerate or do not ben…
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- Pneumocystis jirovecii pneumonia in patients with inflammatory bowel disease - A case series. [Journal Article]J Crohns Colitis. 2022 Oct 12 [Online ahead of print]JC
- CONCLUSIONS: This case series reporting potentially fatal PJP highlights the need for adjusted prophylactic therapy in patients with IBD on immunosuppressive therapy.
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- Transcriptional changes in Plasmodium falciparum upon conditional knock down of mitochondrial ribosomal proteins RSM22 and L23. [Journal Article]
- The mitochondrion of malaria parasites is an attractive antimalarial drug target, which require mitoribosomes to translate genes encoded in the mitochondrial (mt) DNA. Plasmodium mitoribosomes are composed of highly fragmented ribosomal RNA (rRNA) encoded in the mtDNA. All mitoribosomal proteins (MRPs) and other assembly factors are encoded in the nuclear genome. Here, we have studied one putativ…
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- In vivo activity and atom pair fingerprint analysis of MMV665941 against the apicomplexan parasite Babesia microti, the causative agent of babesiosis in humans and rodents. [Journal Article]Pathog Glob Health. 2022 Sep 28 [Online ahead of print]PG
- The effect of MMV665941 on the growth of Babesia microti (B. microti) in mice, was investigated in this study using a fluorescence-based SYBR Green I test. Using atom Pair signatures, we investigated the structural similarity between MMV665941 and the commonly used antibabesial medicines diminazene aceturate (DA), imidocarb dipropionate (ID), or atovaquone (AV). In vitro cultures of Babesia bovis…
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- A Smart Nanoreactor Based on an O2-Economized Dual Energy Inhibition Strategy Armed with Dual Multi-stimuli-Responsive "Doorkeepers" for Enhanced CDT/PTT of Rheumatoid Arthritis. [Journal Article]ACS Nano. 2022 10 25; 16(10):17062-17079.AN
- Activated fibroblast-like synovial (FLS) cells are regarded as an important target for rheumatoid arthritis (RA) treatment via starvation therapy mediated by glucose oxidase (GOx). However, the hypoxic RA-FLS environment greatly reduces the oxidation process of glucose and leads to a poor therapeutic effect of the GOx-based starvation therapy. In this work, we designed a hollow mesoporous copper …
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- Oxygen tank for synergistic hypoxia relief to enhance mitochondria-targeted photodynamic therapy. [Journal Article]
- CONCLUSIONS: This oxygen tank both increases exogeneous oxygen supply and decreases endogenous oxygen consumption, may offer a novel solution for organelle targeted therapies.
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- Global scenario of Plasmodium vivax occurrence and resistance pattern. [Review]J Basic Microbiol. 2022 Dec; 62(12):1417-1428.JB
- Malaria caused by Plasmodium vivax is comparatively less virulent than Plasmodium falciparum, which can also lead to severe disease and death. It shows a wide geographical distribution. Chloroquine serves as a drug of choice, with primaquine as a radical cure. However, with the appearance of resistance to chloroquine and treatment has been shifted to artemisinin combination therapy followed by pr…
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- Repurposing of the Malaria Box for Babesia microti in mice identifies novel active scaffolds against piroplasmosis. [Journal Article]
- CONCLUSIONS: Inhibitory and hematology assay results suggest that MMV396693 and MMV665875 are potent antipiroplasm monotherapies. The structural similarity results indicate that MMV665875 and MMV396693 have a similar mode of action as AV and ID, respectively. Our findings demonstrated that MBox compounds provide a promising lead for the development of new antibabesial therapeutic alternatives.
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- Human Babesiosis. [Review]Infect Dis Clin North Am. 2022 09; 36(3):655-670.ID
- Babesiosis is caused by intraerythrocytic parasites that are transmitted primarily by ticks, infrequently through blood transfusion, and rarely through transplacental transmission or organ transplantation. Human babesiosis is found throughout the world, but the incidence is highest in the Northeast and upper Midwestern United States. Babesiosis has clinical features that resemble malaria and can …
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- Efficacy of three anti-malarial regimens for uncomplicated Plasmodium falciparum malaria in Cambodia, 2009-2011: a randomized controlled trial and brief review. [Review]
- CONCLUSIONS: This study was conducted at the epicentre of substantial multi-drug resistance that emerged soon thereafter. Occurring early in the national transition from AS/MQ to DHA/PPQ, both DHA/PPQ and ATQ/PG had acceptable efficacy against uncomplicated falciparum malaria. However, efficacy of AS/MQ was only 80% with apparent mefloquine resistance based on elevated Pfmdr1 copy number and IC50. By 2009, there was already significant evidence of artemisinin resistance not previously reported at the Northern Cambodia-Thai border. This study suggests the basis for early development of significant DHA/PPQ failures within 3 years of introduction. Artemisinin resistance likely occurred on the Northern border concurrently with that reported along the Western border in Pailin. Trial registration This legacy trial was conducted prior to International Committee of Medical Journal Editors' requirements for preregistration on ClinicalTrials.gov. The full protocol has been provided.
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