This study evaluated the anti-Toxoplasma gondii potential of gold, silver, and platinum nanoparticles (NPs). Inorganic NPs (0.01–1,000 µg/mL) were screened for antiparasitic activity. The NPs caused >90% inhibition of T. gondii growth with EC50 values of ≤7, ≤1, and ≤100 µg/mL for gold, silver, and platinum NPs, respectively. The NPs showed no host cell cytotoxicity at the effective anti-T. gondii concentrations; the estimated selectivity index revealed a ≥20-fold activity toward the parasite versus the host cell. The anti-T. gondii activity of the NPs, which may be linked to redox signaling, affected the parasite mitochondrial membrane potential and parasite invasion, replication, recovery, and infectivity potential. Our results demonstrated the antiparasitic potential of NPs. The findings support the further exploration of NPs as a possible source of alternative and effective anti-T. gondii agents.

The scientific explorations of nanoparticles for their inherent therapeutic potencies as antimicrobial and antiviral agents due to increasing incidences of antibiotic resistance have gained more attention in recent time. This factor amongst others necessitates the search for newer and more effective antimicrobial agents. Several investigations have demonstrated the prospects of nanoparticles in the treatment of various microbial infections. The therapeutic applications of nanoparticles as either delivery agent or broad spectrum inhibition agents in viral and microbial investigations can no longer be overlooked. Their large surface area to volume ratio made them an indispensable substance as delivery agents in many respect. Various materials have been used for the synthesis of nanoparticles with unique properties channelised to meet specific therapeutic requirement. This review focuses on the antibacterial, antifungal, and antiviral potential of nanoparticles with their probable mechanism of action.

Arginine kinase is not only absent from mammalian hosts but is critical to the survival of trypanosomes under stressful conditions and consequently its inhibition may lead to an effective treatment for trypanosomiasis. The His-tagged enzyme was cloned from Trypanosoma brucei genomic DNA, expressed in Escherichia coli BL21 DE3 cells and purified on a Ni-affinity column and by FPLC on a Superdex 200 HR. The enzyme had a specific activity of 2.92 μmol min(-1) mg protein(-1), molecular mass of 40 kDa, temperature and pH optima of 30 °C and 7.8, and Km and Vmax as 2.94 mM and 0.161 μmol ml(-1) min(-1) (arginine substrate). The interaction of the enzyme with silver and gold nanoparticles showed a non-competitive inhibition with, respectively, 75% and 62% decrease in activity; Ki values ranged from 1.5 nM (Ag) to 3.1 nM (Au). A mechanism for this inhibition was by interaction with Cys(271) positioned 3.3 Å from the reactive NH(1) of substrate arginine. This cysteine controls electrophilic and nucleophilic character of the guanidinium group that is crucial for enzymatic phosphoryl transfer between ADP and ATP.

Background Chemotherapy is a principle tool for the control and prevention of piroplasmosis. The search for a new chemotherapy against Babesia and Theileria parasites has become increasingly urgent due to the toxic side effects of and developed resistance to the current drugs. Chalcones have attracted much attention due to their diverse biological activities. With the aim to discover new drugs and drug targets, in vitro and in vivo antibabesial activity of trans -chalcone (TC) and chalcone 4 hydrate (CH) alone and combined with diminazene aceturate (DA), clofazimine (CF) and atovaquone (AQ) were investigated. Methodology/Principal findings The fluorescence-based assay was used for evaluating the inhibitory effect of TC and CH on four Babesia species, including B . bovis , B . bigemina , B . divergens , B . caballi , and T . equi , the combination with DA, CF, and AQ on in vitro cultures, and on the multiplication of a B . microti –infected mouse model. The cytotoxicity of compounds was tested on Madin–Darby bovine kidney (MDBK), mouse embryonic fibroblast (NIH/3T3), and human foreskin fibroblast (HFF) cell lines. The half maximal inhibitory concentration (IC 50 ) values of TC and CH against B . bovis , B . bigemina , B . divergens , B . caballi , and T . equi were 69.6 ± 2.3, 33.3 ± 1.2, 64.8 ± 2.5, 18.9 ± 1.7, and 14.3 ± 1.6 μM and 138.4 ± 4.4, 60.9 ± 1.1, 82.3 ± 2.3, 27.9 ± 1.2, and 19.2 ± 1.5 μM, respectively. In toxicity assays, TC and CH affected the viability of MDBK, NIH/3T3, and HFF cell lines the with half maximum effective concentration (EC 50 ) values of 293.9 ± 2.9, 434.4 ± 2.7, and 498 ± 3.1 μM and 252.7 ± 1.7, 406.3 ± 9.7, and 466 ± 5.7 μM, respectively. In the mouse experiment, TC reduced the peak parasitemia of B . microti by 71.8% when administered intraperitoneally at 25 mg/kg. Combination therapies of TC–DA and TC–CF were more potent against B . microti infection in mice than their monotherapies. Conclusions/Significance In conclusion, both TC and CH inhibited the growth of Babe...

Hypoxia-inducible factors (HIFs) are transcription factors that activate the transcription of genes necessary to circumvent to hypoxic (low oxygen level) environments. In carcinogenesis, HIFs play a critical role. Indeed, HIF-1α has been validated as a promising target for novel cancer therapeutics, even as clinical investigations have linked increased levels of HIF-1α with aggressive cancer progression as well as poor patient prognosis. More so, inhibiting HIF-1 activity restricted cancer progression. Therefore, HIF-1 is a viable target for cancer therapy. This may be expected considering the fact that cancer cells are known to be hypoxic. In order to survive the hypoxic microenvironment, cancer cells activate several biochemical pathways via the HIF-1α. Additionally, cellular and molecular insights have proved prospects of the HIF-1α pathway for the development of novel anticancer treatment strategies. The biochemical importance of hypoxia-inducible factors (HIFs) cannot be overemphasized as carcinogenesis, cancer progression, and HIFs are intricately linked. Therefore, this review highlights the significance of these linkages and also the prospects of HIFs as an alternative source of cancer therapies.

The nanoparticles of silver and gold interact with arginine kinase from T. brucei and may prove to have far reaching consequences in clinical trials.

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Background. Silver nanoparticles have found wider and increasing biomedical applications due to their broad antimicrobial characteristics. However, toxicity of nanoparticles is a subject of continued controversy, thus necessitating further studies in this direction. Objectives. This study investigated the biochemical effects of silver nanoparticles in Wistar rats. Materials and Methods. Forty male rats were randomly distributed into eight experimental groups of five. Group A served as the control and received distilled water. Groups B to H were orally exposed to varying concentrations of silver nanoparticles (AgNPs) at 100, 1000, and 5000 mg/kg daily for 7, 14, and 21 days alternately. Following cessation of treatments, rats were sacrificed and the blood and other vital organs were collected and prepared as specimens for biochemical analysis. Results. Administration of AgNPs to rats did not produce significant loss in feed intake and body weight. However, rat exposure to AgNPs caused significant alterations to levels of serum and tissue AST, ALT, and ALP. At the 100 mg/kg AgNPs exposure, rat serum and tissue AST and ALT levels were significantly decreased (P < 0.05). In contrast, AgNPs administration elevated (P < 0.05) ALP levels in rat serum and tissues. Conclusion. We show evidence that AgNPs administration to Wistar rats altered some biochemical parameters.