Recombinant Expression and Biophysical Characterization of a Druggable Schistosoma mansoni Universal Stress G4LZI3 Protein.

Purpose: Universal stress protein (USP) from Schistosoma mansoni, designated as G4LZI3, waspreviously hypothesised as a druggable target and vaccine candidate for human schistosomiasis.The purpose of this study is to characterize a purified recombinant G4LZI3 preliminarily forsubsequent structural characterization, which will provide baseline structural data for futurefunctional studies for the discovery, design and development of new schistosomal drugs for thetreatment, control and elimination of schistosomiasis. Methods: Restriction digest analysis of a GenScript-synthesised codon-optimised G4LZI3gene construct was carried out to ascertain its integrity and size. Thereafter, the pQE30-G4LZI3 construct was transformed into an M15 bacterial expression host. Transformed cellswere induced with isopropyl ß-D-thiogalactoside for recombinant protein expression of anappreciable amount of pQE30-G4LZI3, which was subsequently purified with fast proteinliquid chromatography (FPLC) and a size exclusion chromatographic purification scheme.Preliminary biophysical characterization of the 6X His-tagged G4LZI3 was done to determineits secondary structure characteristics and protein stability. Results: A molecular weight protein of 20.3 kDa was confirmed subsequent to restriction digestanalysis, while heterologous protein expression yielded a highly soluble and considerableamount of histidine-tagged G4LZI3 protein, which was successfully purified to homogeneity.Biophysical characterization indicated that the protein was well folded, heat-stable, had thefunctional groups and secondary structure composition required and was thus amenable tofurther structural characterization and determination. Conclusion: Biophysical characterization of purified G4LZI3 showed that further structuralstudies can be embarked upon on the use of G4LZI3 as a druggable target and possibly avaccine target against schistosomiasis via vaccinomics.

Universal Stress Proteins as New Targets for Environmental and Therapeutic Interventions of Schistosomiasis.

In spite of various control measures and eradication methods that have been in progress, schistosomiasis still prevails as one of the most prevalent debilitating parasitic diseases, typically affecting the poor and the underprivileged that are predominantly concentrated in sub-Saharan Africa. The parasitic schistosome blood fluke responsible for causing the disease completes its complex developmental cycle in two hosts: humans and freshwater snails, where they physically undergo gross modifications to endure the different conditions associated with each host. Just like any other organism, the worm possesses mechanisms that help them respond to environmental insults. It has been hypothesized that a special class of proteins known as Universal Stress Proteins (USPs) are up-regulated during sudden environmental changes, thus assisting the worm to tolerate the unfavourable conditions associated with its developmental cycle. The position of praziquantel as the drug of choice against all schistosome infections has been deemed vulnerable due to mounting concerns over drug pressure and so the need for alternative treatment is now a matter of urgency. Therefore, this review seeks to explore the associations and possible roles of USPs in schistosomiasis as well as the functioning of these proteins in the schistosomulae stage in order to develop new therapeutic interventions against this disease.

Aqueous extract of Monodora myristica ameliorates cadmium-induced hepatotoxicity in male rats.

In recent years, indigenous medicinal plants exhibiting diverse biological activities have been explored in the amelioration of hepatotoxicity. This study investigates the protective effect of Monodora myristica (MM) on cadmium-induced liver damage in experimental animals. Male Wistar albino rats were maintained on 200 mg/L cadmium: Cd (Cd as CdCl2) in the animals' main drinking water to induce hepatotoxicity. Added to this, the animals received aqueous extracts of MM at a dose of 200 or 400 and 20 mg/kg bw of Livolin forte (LF) for 21 days. At the end of the experiment, levels of serum enzyme biomarkers (alanine transaminase, alkaline phosphatase and aspartate transaminase) as well as total cholesterol (TC), triacylglyceride (TG) and malondialdehyde were significantly raised in the cadmium treated groups. Conversely, cadmium treatment elicited noticeable decrease in hepatic enzymatic and non-enzymatic antioxidants (reduced glutathione: GSH, catalase: CAT, superoxide dismutase: SOD). Co-treatment with MM at varying doses as well as LF considerably decreased the elevated levels of the serum biomarkers as well as TC, TG and malondialdehyde in the cadmium-treated groups in a dose dependant manner. Additionally, MM exhibited reversal potential on cadmium-toxicity at the tested doses as its administration was accompanied by a pronounced increase in GSH, SOD, and CAT levels. Histopathological results were parallel to these findings. These results demonstrates that aqueous extracts of MM is effective in the amelioration of hepatic damages arising from cadmium-induced toxicity, indicating that the antioxidant bio-constituents of MM play an important role in the prevention of liver toxicity possibly by inhibiting bioaccumulation of free radicals in animal models.

Reactive oxygen species, apoptosis, antimicrobial peptides and human inflammatory diseases.

Excessive free radical generation, especially reactive oxygen species (ROS) leading to oxidative stress in the biological system, has been implicated in the pathogenesis and pathological conditions associated with diverse human inflammatory diseases (HIDs). Although inflammation which is considered advantageous is a defensive mechanism in response to xenobiotics and foreign pathogen; as a result of cellular damage arising from oxidative stress, if uncontrolled, it may degenerate to chronic inflammation when the ROS levels exceed the antioxidant capacity. Therefore, in the normal resolution of inflammatory reactions, apoptosis is acknowledged to play a crucial role, while on the other hand, dysregulation in the induction of apoptosis by enhanced ROS production could also result in excessive apoptosis identified in the pathogenesis of HIDs. Apparently, a careful balance must be maintained in this complex environment. Antimicrobial peptides (AMPs) have been proposed in this review as an excellent candidate capable of playing prominent roles in maintaining this balance. Consequently, in novel drug design for the treatment and management of HIDs, AMPs are promising candidates owing to their size and multidimensional properties as well as their wide spectrum of activities and indications of reduced rate of resistance.

Impact of human schistosomiasis in sub-Saharan Africa

Schistosomiasis, a neglected tropical disease of poverty ranks second among the most widespread parasitic disease in various nations in sub-Saharan Africa. Neglected tropical diseases are causes of about 534,000 deaths annually in sub-Saharan Africa and an estimated 57 million disability-adjusted life-years are lost annually due to the neglected tropical diseases. The neglected tropical diseases exert great health, social and financial burden on economies of households and governments. Schistosomiasis has profound negative effects on child development, outcome of pregnancy, and agricultural productivity, thus a key reason why the "bottom 500 million" inhabitants of sub-Saharan Africa continue to live in poverty. In 2008, 17.5 million people were treated globally for schistosomiasis, 11.7 million of those treated were from sub-Saharan Africa. This enervating disease has been successfully eradicated in Japan, as well as in Tunisia. Morocco and some Caribbean Island countries have made significant progress on control and management of this disease. Brazil, China and Egypt are taking steps towards elimination of the disease, while most sub-Saharan countries are still groaning under the burden of the disease. Various factors are responsible for the continuous and persistent transmission of schistosomiasis in sub-Saharan Africa. These include climatic changes and global warming, proximity to water bodies, irrigation and dam construction as well as socio-economic factors such as occupational activities and poverty. The morbidity and mortality caused by this disease cannot be overemphasized. This review is an exposition of human schistosomiasis as it affects the inhabitants of various communities in sub-Sahara African countries. It is hoped this will bring a re-awakening towards efforts to combat this impoverishing disease in terms of vaccines development, alternative drug design, as well as new point-of-care diagnostics.

Impact of human schistosomiasis in sub-Saharan Africa.

Schistosomiasis, a neglected tropical disease of poverty ranks second among the most widespread parasitic disease in various nations in sub-Saharan Africa. Neglected tropical diseases are causes of about 534,000 deaths annually in sub-Saharan Africa and an estimated 57 million disability-adjusted life-years are lost annually due to the neglected tropical diseases. The neglected tropical diseases exert great health, social and financial burden on economies of households and governments. Schistosomiasis has profound negative effects on child development, outcome of pregnancy, and agricultural productivity, thus a key reason why the "bottom 500 million" inhabitants of sub-Saharan Africa continue to live in poverty. In 2008, 17.5 million people were treated globally for schistosomiasis, 11.7 million of those treated were from sub-Saharan Africa. This enervating disease has been successfully eradicated in Japan, as well as in Tunisia. Morocco and some Caribbean Island countries have made significant progress on control and management of this disease. Brazil, China and Egypt are taking steps towards elimination of the disease, while most sub-Saharan countries are still groaning under the burden of the disease. Various factors are responsible for the continuous and persistent transmission of schistosomiasis in sub-Saharan Africa. These include climatic changes and global warming, proximity to water bodies, irrigation and dam construction as well as socio-economic factors such as occupational activities and poverty. The morbidity and mortality caused by this disease cannot be overemphasized. This review is an exposition of human schistosomiasis as it affects the inhabitants of various communities in sub-Sahara African countries. It is hoped this will bring a re-awakening towards efforts to combat this impoverishing disease in terms of vaccines development, alternative drug design, as well as new point-of-care diagnostics.