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.
Heat shock proteins (HSPs) play cytoprotective activities under pathological conditions through the initiation of protein folding, repair, refolding of misfolded peptides, and possible degradation of irreparable proteins. Excessive apoptosis, resulting from increased reactive oxygen species (ROS) cellular levels and subsequent amplified inflammatory reactions, is well known in the pathogenesis and progression of several human inflammatory diseases (HIDs) and cancer. Under normal physiological conditions, ROS levels and inflammatory reactions are kept in check for the cellular benefits of fighting off infectious agents through antioxidant mechanisms; however, this balance can be disrupted under pathological conditions, thus leading to oxidative stress and massive cellular destruction. Therefore, it becomes apparent that the interplay between oxidant-apoptosis-inflammation is critical in the dysfunction of the antioxidant system and, most importantly, in the progression of HIDs. Hence, there is a need to maintain careful balance between the oxidant-antioxidant inflammatory status in the human body. HSPs are known to modulate the effects of inflammation cascades leading to the endogenous generation of ROS and intrinsic apoptosis through inhibition of pro-inflammatory factors, thereby playing crucial roles in the pathogenesis of HIDs and cancer. We propose that careful induction of HSPs in HIDs and cancer, especially prior to inflammation, will provide good therapeutics in the management and treatment of HIDs and cancer.
Modulating disease-relevant protein-protein interactions (PPIs) using small-molecule inhibitors is a quite indispensable diagnostic and therapeutic strategy in averting pathophysiological cues and disease progression. Over the years, targeting intracellular PPIs as drug design targets has been a challenging task owing to their highly dynamic and expansive interfacial areas (flat, featureless and relatively large). However, advances in PPI-focused drug discovery technology have been reported and a few drugs are already on the market, with some potential drug-like candidates already in clinical trials. In this article, we review the advances, successes and remaining challenges in the application of small molecules as valuable PPI modulators in disease diagnosis and therapeutics.
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.
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