Human serum albumin, the primary transport and reservoir protein in the human circulatory system, interacts with numerous endogenous and exogenous ligands of varying structural characteristics. The mode of binding of drugs to albumin is central to understanding their pharmacokinetic profiles and has a major influence on their in vivo efficacy. Altered drug binding to albumin due to drug-drug interactions or abnormal physiology may result in marked changes in the active drug concentration, thus affecting its pharmacokinetic and pharmacodynamic properties. The propensity of drug-drug interaction to be clinically significant as well as possible exploitation of such interactions for therapeutic purposes is reviewed. Being the major organs of albumin metabolism, any impairment in the liver and kidney functions frequently alter the level of serum albumin, which affects the pharmacokinetic profiles of drugs and may have serious clinical implications. The natural function of serum albumin as a drug carrier is facilitated by its interaction with various cellular receptors. These receptors not only promote the uptake of drugs into cells but are also responsible for the extraordinarily long circulatory half-life of albumin. This property in combination with the presence of multiple ligand binding pockets have led to the emergence of serum albumin as an attractive vehicle for novel drug delivery systems. Here, we provide an overview of various albumin-based drug delivery strategies, classified according to their methods of drug attachment, and highlight their experimental and clinical successes.
Snake envenomation is listed as Category A Neglected Tropical Diseases (NTD) by World Health Organization, indicates a severe public health problem. The global figures for envenomation cases are estimated to be more than 1.8 million annually. Even if the affected victims survive the envenomation, they might suffer from permanent morbidity due to local envenomation. One of the most prominent local envenomation is dermonecrosis. Dermonecrosis is a pathophysiological outcome of envenomation that often causes disability in the victims due to surgical amputations, deformities, contracture, and chronic ulceration. The key venom toxins associated with this local symptom are mainly attributed to substantial levels of enzymatic and non-enzymatic toxins as well as their possible synergistic actions. Despite so, the severity of the local tissue damage is based on macroscopic observation of the bite areas. Furthermore, limited knowledge is known about the key biomarkers involved in the pathogenesis of dermonecrosis. The current immunotherapy with antivenom is also ineffective against dermonecrosis. These local effects eventually end up as sequelae. There is also a global shortage of toxins-targeted therapeutics attributed to inadequate knowledge of the actual molecular mechanisms of cytotoxicity. This chapter discusses the characterization of secretory phenotypes of dermonecrosis as an advanced tool to indicate its severity and pathogenesis in envenomation. Altogether, the secretory phenotypes of envenomed cells and tissues represent the precise characteristics of dermonecrosis caused by venom toxins.
Circadian rhythms are autonomous oscillators developed by the molecular circadian clock, essential for coordinating internal time with the external environment in a 24-h daily cycle. In mammals, this circadian clock system plays a major role in all physiological processes and severely affects human health. The regulation of the circadian clock extends beyond the clock genes to involve several clock-controlled genes. Hence, the aberrant expression of these clock genes leads to the downregulation of important targets that control the cell cycle and the ability to undergo apoptosis. This may lead to genomic instability and promotes carcinogenesis. Alteration in the clock genes and their modulation is recognized as a new approach for the development of effective treatment against several diseases, including cancer. Until now, there has been a lack of understanding of circadian rhythms and cancer disease. For that, this chapter aims to represent the core components of circadian rhythms and their function in cancer pathogenesis and progression. In addition, the clinical impacts, current clock drugs, and potential therapeutic targets have been discussed.
Osteosarcoma is a malignant osseous neoplasm. Osteosarcoma is a primary bone malignancy capable of producing osteoid tissue or immature bones. A subsequent malignant degeneration of the primary bone pathology occurs less frequently in adults. The over-expression of several proteins, including Heat shock proteins, Cofilin, Annexins, Insulin-like growth factor, transforming growth factor-β, Receptor tyrosine kinase, Ezrin, Runx2, SATB2, ATF4, Annexins, cofilin, EGFR, VEGF, retinoblastoma 1 (Rb1) and secreted protein, has been associated to the development and progression of osteosarcoma. These proteins are involved in cell adhesion, migration, invasion, and the control of cell cycle and apoptosis. In genomic studies, osteosarcoma has been associated with several genetic abnormalities, including chromosomal rearrangements, gene mutations, and gene amplifications. These differentially expressed proteins could be used as early identification biomarkers or treatment targets. Proteomics and genomics play significant parts in enhancing our molecular understanding of osteosarcoma, and their integration provides essential insights into this aggressive bone cancer. This review will discuss the tumour biology that has assisted in helping us better understand the causes of osteosarcoma and how they could potentially be used to find new treatment targets and enhance the survival rate for osteosarcoma patients.