Current Drug Targets - Volume 19, Issue 14, 2018

Background: Parkinson's disease (PD) is a neurodegenerative disease characterized by the loss of dopaminergic neurons within the substantia nigra pars compacta (SNpc). Despite many researches, there is still no cure for this disease. Levodopa is the first line treatment of PD, but the long term use of it leads to motor impairments and dyskinesias. The dopamine agonists are the preferred choice for the treatment of PD. They are neuroprotective in nature but have side effects. Objective: Our aim was to review the work that has been carried out on dopamine agonists and the future possibilities to reduce their side effects. Conclusion: In this review, we highlighted the metabolism of dopamine, different types of dopamine agonists with their properties and possible side effects.

Nowadays, growing interest in the possibility of prophylactic and therapeutic use of plant products rich in biologically active compounds has been observed. Among them, special interest has been focused on polyphenol-rich products. Owing to the multidirectional favourable action of polyphenols, products rich in these compounds are recommended as functional food in the case of civilization diseases. Moreover, data from studies in animal models show that polyphenols may be a promising preventive/therapeutic strategy for xenobiotics, including toxic heavy metals. The protective impact of polyphenols against metal toxicity may be explained by the presence of many hydroxyl groups in the structure of these compounds, which are capable of forming complexes with metals preventing as a result from their gastrointestinal absorption and accelerating their elimination from the body with urine. However, it should be taken into account that polyphenols may bind not only ions of toxic metals, but also bioelements, what makes a risk of their shortage in the organism. This review provides an overview of implications for humans' and animals' health of complexation of bioelements and toxic metals by polyphenols present in the popular foodstuffs, including phenolic acids, cyanidin derivatives, delphinidin, quercetin, kaempferol, morin, epigallocatechin-3-gallate, and curcumin. Polyphenolic compounds capable of binding both necessary and toxic metals occur in commonly consumed products such as green tea, and some fruit and vegetables, including chokeberries, bilberries, and black currant fruit, grapes, and apples, as well as onion. The mechanisms of complexation of essential and toxic metals by polyphenols and possible implications of these for health are discussed.

Background: Stem cell therapy was established as a promising approach for regenerative medicine applications such as cardiac repair. However, current stem cell-based therapeutic strategies have serious challenges such as low retention and viability of transplanted stem cells in the injured myocardium. This significantly limits efficiency of stem cell therapy. In addition, poor knowledge about the fate and survival of stem cells after transplantation represents a major reason of conflicting results from recent clinical studies. Objective: The purpose of review is to highlight key properties and possible applications of nanoparticles for therapeutic approaches utilizing stem cells for cardiac repair. Results: Nanoparticles that are widely used in various biomedical applications may serve as a valuable tool for overcoming these obstacles. Various types of nanoparticles could be efficiently used for delivery of genes that enhance survival and regenerative capacity and decrease apoptosis of transplanted stem cells in the adverse ischemic microenvironment. Furthermore, modification of nanoparticles with chemical agents and/or specific proteins and peptides greatly increases the possibility of targeted transfer of a cargo. Nanoparticles can also greatly facilitate in vivo monitoring of stem cell tracking. Using multimodality hybrid nanosized agents, it is possible to obtain detailed characterization of the post-transplantation behavior of stem cell engrafts. Conclusion: Using of nanocarriers may be very helpful to trigger the efficiency of cardiovascular stem cell biology. It is important however to keep in the mind safety and compatibility of implementation of nanoparticles to proceed to clinical trials.

Introduction: Several reports attest the feasibility and the favorable outcomes of kinase inhibitors administration through feeding tubes or Percutaneous Endoscopic Gastrostomies (PEG), mainly in Non-Small Cell Lung Cancer (NSCLC) patients exposed to first-generation compounds. Here we present the case of an ALK-positive NSCLC patient who achieved cerebral and extra-cranial disease response with ceritinib (a novel ALK inhibitor) administered through a Nasogastric Tube (NGT). We moreover provide a review gathering clinical successes obtained with targeted agents intake through NGT or PEG. Case Presentation: A 53-year-old never-smoker woman was diagnosed with ALK-rearranged stage IV lung adenocarcinoma. After a brilliant response to crizotinib and several lines of systemic therapy, NGT positioning intended for ceritinib administration was required, given the development of a pleuro-esophageal fistula. Enteral drug administration allowed a significant reduction of hepatic and cerebral disease localizations. Literature review and discussion: The majority of kinase inhibitors administration through NGT or PEG accounts for EGFR-mutated (seven) or ALK-positive (seven, including our report) NSCLC patients. Five additional cases concerning different malignancies were described. Enteral drug administration was mostly required by disease-related respiratory impairment, requiring mechanical ventilation in the emergency setting. In our case, the cerebral and extra-cranial response obtained with enteral ceritinib intake suggests the proposition of novel inhibitors in these circumstances may take place after first-generation compounds failure or even upfront. Indeed, their grater potency and activity against brain metastases point out the role of their enteral administration in the first-line setting too, when a rapid systemic and intra-cerebral disease response is required.

Background: Eurycoma longifolia (E. longifolia) has gained widespread recognition due to its versatile pharmacological activities including aphrodisiac, anticancer, antimicrobial, antioxidant, anti-inflammatory, anxiolytic, anti-diabetic, ergogenic, insecticidal, anti-rheumatism, bone protection, and anti-ulcer effects. Objective: This review was aimed to critically overview the literature and summarizes the antibacterial, antiprotozoal, and antifungal trends of E. longifolia and its medicinally active components. Results: Besides its well-documented safety, efficacy, and tolerability, a plethora of in vitro, in vivo, and human clinical studies has evidenced the antimicrobial efficacy of E. longifolia and its bioactive constituents. Phytochemical screening of various types of extracts (methanolic, ethyl acetate, and nbutanolic) from different parts (roots, stem, and leaves) of E. longifolia displayed a dose-dependent antibacterial, antiprotozoal, and antifungal responses. Comparative analysis revealed that the root extract of E. longifolia exhibited the highest antimicrobial efficacy compared to other parts of the plant. Bioactivity-guided fractionation identified that among all of the medicinal compounds isolated/ extracted from different parts of E. longifolia, eurycomanone displayed the strongest antibacterial, antiprotozoal and antifungal activities. Conclusion: Based on the critical analysis of the literature, we identified that E. longifolia exhibits promising antibacterial, antiprotozoal, and antifungal efficacies against various pathogenic microbes and thus can be considered as a potential complementary and alternative antimicrobial therapy.

Obesity is a prominent risk factor for type 2 diabetes. Management of type 2 diabetes requires weight management in addition to glycemic parameters. For obese type 2 diabetes patients, metformin, Sodium-glucose co-transporter-2 inhibitors or Glucagon-Like Peptide-1 Receptor Agonists should be prescribed as the first priority for controlling both hyperglycemia and body weight or fat distribution. The combination of these drugs with sulfonylureas, thiazolidinediones, and insulin may also be required in chronic cases. These drugs cause weight gain. Fortunately, many phytochemicals having a beneficial effect on diabetes and obesity, have minimum side-effects as compared to synthetic drugs. This review discusses the treatment strategies for controlling glycemia and weight management, with the focus on anti-diabetic drugs and phytochemicals. Glucagonostatic role, activation of Adenosine monophosphate-activated protein kinase and adipocyte targeting potential of anti-diabetic drugs and phytochemicals are also discussed.

Major breakthroughs in the last several decades have contributed to our knowledge of the genetic regulation in development. Although epigenetics is not a new concept, unfortunately, the role of epigenetics has not come to fruition in the past. But the field of epigenetics has exploded within the past decade. Now, growing evidences show a complex network of epigenetic regulation in development. The epigenetic makeup of a cell, tissue or individual is much more complex than their genetic complement. Epigenetic modifications are more important for normal development by maintaining the gene expression pattern in tissue- and context-specific manner. Deregulation of epigenetic mechanism can lead to altered gene expression and its function, which result in altered tissue specific function of cells and malignant transformation. Epigenetic modifications directly shape Hematopoietic Stem Cell (HSC) developmental cascades, including their maintenance of self-renewal and multilineage potential, lineage commitment, and aging. Hence, there is a growing admiration for epigenetic players and their regulatory function in haematopoiesis. Epigenetic mechanisms underlying these modifications in mammalian genome are still not completely understood. This review mainly explains 3 key epigenetics mechanisms including DNA methylation, histone modifications and non-coding RNAs inference in hematopoietic lineage commitment and differentiation.

In the United States, the estimated number of new cancer cases in 2018 will be approx. 1.7 million. Historically, combination chemotherapy has been the primary choice of treatment. However, chemotherapeutics have pharmaceutical limitations, among which include problems with stability and aqueous solubility. Likewise, dose limiting toxicity is significant with nonspecific toxicity to healthy cells, hair loss, loss of appetite, peripheral neuropathy and diarrhea being typical side effects. The emergence of Multidrug resistance (MDR) also presents s a significant challenge for the successful treatment of cancer whereby cancer cells become cross resistant to many of the chemotherapeutic agents used. Nanotechnology presents a new frontier for cancer treatment. It holds potential in minimizing systemic toxicity through the development of functionalized particles for targeted treatment. They also provide an alternative strategy to circumvent multidrug resistance as they have a capacity to by-pass the drug efflux mechanism associated with this phenotype. Aside from the advantages they offer in treatment, nanoparticles are also emerging to be valuable diagnostic entities. This article highlights the various ways nanotechnology is being used to improve the treatment and management of cancer. We also discuss the opportunities and obstacles in this area and provide an up to date review of progress in the treatment of cancer.

Brain ischemia is among the leading cause of death with majority of the cases are associated with ischemic strokes. It can occur in two forms of either focal or global ischemia. Neurodegenerative disorder such as Alzheimer and Parkinson diseases is also on the rise worldwide. These disorders have common similarities; i.e. they all affecting the central nervous system with debilitating effect to the patient. In this review, we look into the promising role of flavonoids, a natural bioactive compound found abundant in vegetables, fruits and traditional herbs. Treatment with flavonoids such as curcumin, lycopene, ginsenoside, vitexin and baicalin have shown promising neuroprotective effects against ischemic-induced injury. Besides anticancer, antioxidant and immunomodulation properties, flavonoid also exerts neuroprotective effects by increases neuronal viability, increases tissue perfusion and cerebral blood flow and reduce ischemic-related apoptosis. In addition, flavonoid also exerts anti-amyloidogenic effect and reduces loss of dopaminergic neurons in the brain. These results suggesting flavonoids might be able to serve as a potential therapeutic agent in brain disorders.

Background: Liquid biopsy is a minimally invasive detection method for molecular biomarkers such as miRNA and cell free DNA in body fluids. Deregulations of miRNA are involved in papillary thyroid carcinoma (PTC), one the most common endocrine malignancy. The most widespread common mutations detected in papillary thyroid cancers are BRAF mutations. Many studies indicate that the BRAF mutation is related to deregulation of miRNA. p53 has an important role in cell cycle control, DNA repair and apoptosis. Moreover, the p53 can regulate the expression of miRNAs and thus participate in thyroid oncogenesis. Objective: In this review, we briefly summarize the present state of knowledge about miRNA, BRAF and p53 mutation in the development of PTC and the possibility of using detecting BRAF mutation and miRNA expression in liquid biopsy. Results: The use of the plasma miRNA expression profile in combination with the BRAF mutation analysis in cf-DNA may be a valuable tool in management of PTC. Conclusion: Numerous molecular variation characterize recent diagnostic and prognostic markers and therapeutic targets for this type of cancer, which offer unique chances for further research and clinical development of innovative treatment strategies for thyroid cancer.