Current Drug Targets - Volume 19, Issue 13, 2018

Diabetes mellitus is one of the leading causes of death worldwide. Loss and functional failure of pancreatic β-cells, the parenchyma cells in the islets of Langerhans, progress diabetes mellitus. The increasing incidence of this metabolic disorder necessitates efficient strategies to produce functional β-cells for treating diabetes mellitus. Human induced Pluripotent Stem Cells (hiPSC), hold potential for treating diabetes ownig to their self-renewal capacity and the ability to differentiate into β- cells. iPSC technology also provides unlimited starting material to generate differentiated cells for regenerative applications. Progress has also been made in establishing in-vitro culture protocols to yield definitive endoderm, pancreatic endoderm progenitor cells and β-cells via different reprogramming strategies and growth factor supplementation. However, these generated β-cells are still immature, lack functional characteristics and exhibit lower capability in reversing the diseases conditions. Current methods employed to generate mature and functional β-cells include; use of small and large molecules to enhance the reprogramming and differentiation efficiency, 3D culture systems to improve the functional properties and heterogeneity of differentiated cells. This review details recent advancements in the generation of mature β-cells by reprogramming stem cells into iPSCs that are further programmed to β-cells. It also provides deeper insight into current reprogramming protocols and their efficacy, focusing on the underlying mechanism of chemical-based approach to generate iPSCs. Furthermore, we have highlighted the recent differentiation strategies both in-vitro and in-vivo to date and the future prospects in the generation of mature β-cells.

Background: Heat Shock Proteins (HSPs) constitute a group of proteins that play a crucial role in the process of protein folding. HSPs are also known to modulate a number of key apoptotic factors. High expression of these proteins is reported in an array of cancers, such as breast, prostate, colorectal, lung, ovarian, gastric, oral and esophageal cancer. Ample amount of investigations were carried out on a variety of cancers suggesting HSPs as a promising hallmark in cancers. Their expression profile in several tumors elucidates that they help in proliferation, invasion, metastasis and death of cancerous cells. Detection of the levels of heat shock proteins and their specific antibodies in the sera of diseased individuals can play an important role in cancer diagnosis. Objectives: This review will present and summarize latest research being carried out on heat shock proteins. It will also highlight the clinical and prognostic features of HSP27, HSP60, HSP70, HSP90 and HSP110, and will discuss future implications of HSPs in the diagnosis and prognosis of cancer. Furthermore, the role of heat shock proteins as a therapeutic target in cancer will be discussed. In addition, the review article will report various studies, where HSPs have been targeted for their therapeutic potential. Conclusion: In summary, multiple experimental investigations have been successful in suggesting the role of heat shock protein as a clinical biomarker and therapeutic target in cancer. HSPs are associated with a number of cancer hallmarks such as cell proliferation, invasion and metastasis. Inhibition of HSPs has resulted in successful therapeutic outcome in cancer. It has served as a novel anti-cancer therapy for the treatment of several cancer forms. However, more experimental studies are required to elucidate the reliability and efficacy of heat shock proteins in combination with other conventional markers for cancer diagnosis and prognosis. Novel and effective interventions through HSP inhibition are expected to decrease the burden of cancer in the near future.

Background: Glycan-binding proteins are widely distributed in human and play an essential role in biological processes. Their involvements in inflammatory and immune responses make it increasingly likely that the glycan-binding proteins may represent valuable therapeutic targets. Objective: The current review aims to provide information on recent advancements in clinical developments of antibodies against glycan-binding proteins as potential targets. Results and Conclusion: There are several therapeutic antibodies being developed targeting glycanbinding proteins, including CD22, CD33, DEC-205, and CD62P, for different diseases. The clinical investigations demonstrated benefits of treatments with one antibody-drug conjugate against CD22 being approved by the regulatory agencies. The recent progresses in clinical developments of these antibodies have provided great promises in therapeutic targeting of more glycan-binding proteins for treating multiple diseases, including inflammation, autoimmune diseases, and hematological malignancies.

Background: Nanotechnology deals with the manufacturing of materials at the atomic and molecular scale. According to the National Nanotechnology Initiative, nanotechnology denotes those structures which are nearly in 1−100 nm size regime in at least one dimension. Objective: Nanotechnology in drug delivery has been evidenced into nanocarriers that possess distinct properties both in vitro and in vivo, which may be used in targeting drugs to various diseases especially tumors. In the last few years, there has been a keen concern in the formulation of various new drug delivery systems employing nanotechnology. Different nanodevices or nanocarriers like liposomes, dendrimers, polymersomes, transfersomes, and nanoparticles etc. have been employed for the targeted drug delivery. Conclusion: This review summarizes the advances in nanocarriers in terms of their methods of preparation and potential applications especially in tumors.

Background: The liver is the largest and vital organ present in all vertebrates. It performs various major functions such as detoxification, metabolism, protein synthesis, excretion and so on. Liver cells are divided into parenchymal cells and non-parenchymal cells. Hepatocytes, Kupffer cells, hepatic stellate cells and sinusoidal endothelial cells, etc. are found in liver having different receptors present on their surface which can be used for liver targeting by binding to different ligands. Objective: In this review, we focused on various factors such as drugs, plants; metals and so on are reported in literature to be responsible for causing hepatotoxicity, natural hepatoprotective agents and liver targeting via novel formulation approaches. Conclusion: All over the world, millions of people are affected by serious liver disorders which are very difficult to treat despite of many efforts. Hepatotoxicity is one of the major reasons due to which drugs continue to be taken off from the market. This review highlights the potential of various phytochemicals as hepatoprotective agents and various strategies which have been proposed to achieve liver targeting, including passive accumulation of therapeutic drug delivery system and active targeting by surface modifications of particulate formulation with specific ligands.

Evidence-based review of the existing literature ultimately recommends stocking of Methylene Blue (MB) as an emergency antidote in the United States. The same is reported around the world in Japan, Greece, Italy and Canada. The observation that MB is always present as the main antidote required in emergency and critical care units calls for a revisit on its effects on the NO/cGMP system to reemphasize its multisystem actions. Therefore, the present review aimed to display the role of MB in emergency units, concerning: 1) Polytrauma and circulatory shock; 2) Neuroprotection, 3) Anaphylaxis and, 4) Overdose and poisoning.

Background: Tremendous efforts through dedicated research have been made for the development of robust, point of care, portable, cost effective, sensitive and specific assays of microbial detection. Biosensing and nanotechnology offer novel strategies of designing state of the art devices and assay formats with enhanced sensitivity and all other desired features. Monoclonal antibodies have been in use as biorecognition elements for decades. However, recent studies have demonstrated superiority of aptamers to monoclonal antibodies in a number of applications. Many of the research groups have successfully utilized aptamers as capture probes in developing biosensors for microbial detection. Objectives: The main objective of this review article is to present the reader with an overview of the recent advances made in the field of aptamers and aptasensors for the detection and identification of microbial agents. Results: Our search for relevant information on current advances on aptamers and aptasensors has revealed that a number of successful attempts have been made in the last two decades for the selection of aptamers as well as their applications in aptasensors for microbial detection. Conclusion: Aptamers and aptasensors, although in their infancy, may find promising application in rapid, sensitive, point of care and cost effective microbial detection.

Background and Objective: Tumor growth, development, progression, metastasis, invasion and resistivity against drugs solely depend on the recruitment of surrounding cells, extracellular matrix and Tumor Microenvironment (TME). TME is directly as well as indirectly associated with Cancer- Associated Fibroblasts (CAF). The interactions of CAF with tumor surrounding cells, their origination, activation, transformation and ability to recruit other non-tumor cells for the clemency of tumor, are very complex and under active research since long. This study provides an in-depth review of CAF and highlights its potential targets for the regulation of TME as well as discusses current drugs in clinical trials, targeting through CAF. Conclusion: The potential role of CAF in anti-tumor therapy is based on its coherent response against drugs, targeting different tumor sections through these genetically more stable and anti-immunosupportive CAF cells. CAF can be targeted through immunity system; Growth Factors (GF) including Transforming growth factor (TGF), vascular endothelial GF, fibroblast GF, platelet derived GF; and TME elements including hypoxia, carbonic anhydrase, extracellular matrix (ECM). Collectively these features of CAF make it most vulnerable against single as well as combinational, anti-tumor therapy for synergistic or additive effects. Potential activities of CAF, their origination mechanisms and identification of meticulous bio-markers are needed to be investigated further. The rousing facts about them mutually culminate the anticipation of progress towards novel therapeutic establishment against cancer through CAFs that are under progressive research at all levels including, pre-clinical and clinical trials as well as possess much potential to be explored further.

Background: Due to increase in antibiotic-resistance among pathogens, there is a need for potent and safe drugs. An alternative to antibiotics is lipopeptides which are produced as a secondary metabolite by many microorganisms. They exhibit broad-spectrum activities against pathogens along with anticancer properties. Among various lipopeptides produced by microorganisms, daptomycin, surfactin, and polymyxin have gained popularity as medicines but their mechanism of action is not described properly. In silico drug design of these lipopeptides becomes a challenge due to their complex structures. In order to initiate a physiological response, specific agonists (ligands) of their receptor (lipopeptide) must be identified. Objective: The objective of this study was molecular docking of three lipopeptides, daptomycin, surfactin and polymyxin, with their ligands as a means of drug design. Method: Schrödinger software was used for molecular docking of lipopeptides with their corresponding ligands whereas the ligand search was done using RCSB. Once the ligands were identified, they were docked with their corresponding lipopeptide. Docking score and glide energy were used as the parameters to test docking. Results: All four of the identified ligands were found to dock with daptomycin, whereas for both surfactin and polymyxin one out of two ligands docked with the lipopeptides. Conclusion: The knowledge of the docking sites and docking characteristics of the lipopeptide mentioned in the paper with the ligands can provide advantages of high speed and reliability, reduced costs on chemicals and experiments and the ethical issues concerned with the use of animal models for screening of drug toxicity.