Lead poisoning has been recognized as a major public health risk, particularly in developing countries. Though various occupational and public health measures have been undertaken in order to control lead exposure, cases of lead poisoning are still reported. Exposure to lead produces various deleterious effects on the hematopoietic, renal, reproductive and central nervous system, mainly through increased oxidative stress. These alterations play a prominent role in disease manifestations. Modulation of cellular thiols for protection against reactive oxygen species (ROS) has been used as a therapeutic strategy against lead poisoning. N-acetylcysteine, α-lipoic acid, vitamin E, quercetin and a few herbal extracts show prophylaxis against the majority of lead mediated injury in both invitro and in vivo studies. This review provides a comprehensive account of recent updates describing health effects of lead exposure, relevant biomarkers and mechanisms involved in lead toxicity. It also updates the readers about recent advances in chelation therapy and newer therapeutic strategies, like nanoencapsulation, to treat lead induced toxic manifestations.

Cardiovascular diseases (CVDs) are the leading cause of premature death and disability in humans and their incidence is on the rise globally. Given their substantial contribution towards the escalating costs of health care, CVDs also generate a high socio-economic burden in the general population. The underlying pathogenesis and progression associated with nearly all CVDs are predominantly of atherosclerotic origin that leads to the development of coronary artery disease, cerebrovascular disease, venous thromboembolism and, peripheral vascular disease, subsequently causing myocardial infarction, cardiac arrhythmias or stroke. The aetiological risk factors leading to the onset of CVDs are well recognized and include hyperlipidaemia, hypertension, diabetes, obesity, smoking and, lack of physical activity. They collectively represent more than 90% of the CVD risks in all epidemiological studies. Despite high fatality rate of CVDs, the identification and careful prevention of the underlying risk factors can significantly reduce the global epidemic of CVDs. Beside making favorable lifestyle modifications, primary regimes for the prevention and treatment of CVDs include lipid-lowering drugs, antihypertensives, antiplatelet and anticoagulation therapies. Despite their effectiveness, significant gaps in the treatment of CVDs remain. In this review, we discuss the epidemiology and pathology of the major CVDs that are prevalent globally. We also determine the contribution of well-recognized risk factors towards the development of CVDs and the prevention strategies. In the end, therapies for the control and treatment of CVDs are discussed.

There has been a significant rise in the levels of heavy metals (Pb, As, Hg and Cd) due to their increased industrial usage causing a severe concern to public health. The accumulation of heavy metals generates oxidative stress in the body causing fatal effects to important biological processes leading to cell death. Therefore, there is an imperative need to explore efficient and effective methods for the eradication of these heavy metals as against the conventionally used uneconomical and time consuming strategies that have numerous environmental hazards. One such eco-friendly, low cost and efficient alternative to target heavy metals is bioremediation technology that utilizes various microorganisms, green plants or enzymes for the abolition of heavy metals from polluted sites. This review comprehensively discusses toxicological manifestations of heavy metals along with the detailed description of bioremediation technologies employed such as phytoremediation and biosorption for the potential removal of these metals. It also updates readers about recent advances in bioremediation technologies like the use of nanoparticles, non-living biomass and transgenic crops.

Curcumin, a naturally occurring polyphenolic compound, is known to have a wide range of therapeutic and pharmacological properties. Although it is a considerably promising compound, its poor water solubility and fast degradation profile make it compromise over its bioavailability way below the threshold level on administration. Over a period of time, a lot of emphasis has been given to improve the biodistribution of native curcumin, but it is only recently that the application of the field of nanotherapeutics has significantly improved its therapeutic efficacy. This is through the development of nanorange formulations of curcumin, popularly known as the "nanocurcumin." These attempts have given a strong platform to reap all the biological benefits from this phytodrug, which was not significantly plausible earlier. This review gives an insight into the reasons that make nanocurcumin a more therapeutically advanced drug than its native counterpart. It also discusses various nanometric formulations of curcumin that have been reported for its controlled and targeted delivery along with a critical comparison of its therapeutic efficacy with free curcumin. We also summarize the biological applications, patented technologies, and current status of the ongoing clinical trials related to nanocurcumin.

Very little is known about the role of metabolic regulatory mechanisms in platelet activation and thrombosis. Dimeric pyruvate kinase M2 (PKM2) is a crucial regulator of aerobic glycolysis that facilitates the production of lactate and metabolic reprogramming. Herein, we report that limiting PKM2 dimer formation, using the small molecule inhibitor ML265, negatively regulates lactate production and glucose uptake in human and murine stimulated platelets. Furthermore, limiting PKM2 dimer formation reduced agonist-induced platelet activation, aggregation, clot retraction, and thrombus formation under arterial shear stress in vitro in both human and murine platelets. Mechanistically, limiting PKM2 dimerization downregulated phosphatidylinositol 3-kinase (PI3K)-mediated protein kinase B or serine/threonine-specific protein kinase (Akt)/glycogen synthase kinase 3 (GSK3) signaling in human and murine platelets. To provide further evidence for the role of PKM2 in platelet function, we generated a megakaryocyte or platelet-specific PKM2−/− mutant strain (PKM2fl/flPF4Cre+). Platelet-specific PKM2-deficient mice exhibited impaired agonist-induced platelet activation, aggregation, clot retraction, and PI3K-mediated Akt/GSK3 signaling and were less susceptible to arterial thrombosis in FeCl3 injury–induced carotid- and laser injury–induced mesenteric artery thrombosis models, without altering hemostasis. Wild-type mice treated with ML265 were less susceptible to arterial thrombosis with unaltered tail bleeding times. These findings reveal a major role for PKM2 in coordinating multiple aspects of platelet function, from metabolism to cellular signaling to thrombosis, and implicate PKM2 as a potential target for antithrombotic therapeutic intervention.