Current Medicinal Chemistry - Volume 26, Issue 31, 2019

Cancer-related Cachexia (CAC) is a syndrome occurring in many cancer patients, with a detrimental effect on their survival. Recent reports have outlined that the syndrome may be partly explained by the deleterious and pro-inflammatory action of Reactive Oxygen Species (ROS). This review focuses on nutrients that theoretically could counteract the oxidative stress in tumor cells, fundamentally due to their antioxidant activity. The preclinical and clinical results obtained with the nutritional elements selenium, melatonin, taurine, carnosine, coenzyme Q10 (ubiquinone), and omega-3 polyunsaturated fatty acids (PUFA's) are discussed in the light of the pathophysiology of CAC. This should indicate that they are viable candidates for the treatment of CAC, with the ultimate goal to promote patient survival. Combination therapy with diet modification added to the novel pharmaceutical agent ghrelin, a hormone with anti-inflammatory properties, represents a promising concept.

Background: Cancer is a widespread disease and has a high mortality rate. Popular conventional treatment encompasses chemotherapy, radiation and surgical resection. However, these treatments impart lots of toxicity problems to the patients mostly due to their non-selectiveness nature, which invokes drug resistances and severe side-effects. Objectives: In this regard, nanotechnology has claimed to be a smart technology that provides the system with the ability to target drugs to the specific sites. With the use of nanotechnology, various nanomaterials that are widely used as a drug delivery vehicle are created for biomedical applications. Amongst variously diversified nanovehicles, mesoporous silica nanoparticles (MSNs) have attracted enormous attention due to their structural characteristics, great surface areas, tunable pore diameters, good thermal and chemical stability, excellent biocompatibility along with ease of surface modification. Furthermore, the drug release from MSNs can be tailored through various stimuli response gatekeeper systems. The ordered structure of MSNs is extremely suitable for loading of the high amount of drug molecules with controlled delivery for targeting the cancer tissues via enhanced permeability and retention effect or further with surface modification, it can also be actively targeted by various ligands. Methods: The review article emphases the common synthetic methods and current advancement of MSNs usages for stimuli response drug delivery, immunotherapy as well as the theranostic ability for cancer. Conclusion: Although MSNs are becoming the promising tool for more efficient and safer cancer therapy, however, additional translational studies are required to explore its multifunctional ability in a clinical setting.

Background: Nitric Oxide (NO) is a key signalling molecule that has an important role in inflammation. It can be secreted by endothelial cells, neutrophils, and other cells, and once in circulation, NO plays important roles in regulating various neutrophil cellular activities and fate. Objective: To describe neutrophil cellular responses influenced by NO and its concomitant compound peroxynitrite and signalling mechanisms for neutrophil apoptosis. Methods: Literature was reviewed to assess the effects of NO on neutrophils. Results: NO plays an important role in various neutrophil cellular activities and interaction with other cells. The characteristic cellular activities of neutrophils are adhesion and phagocytosis. NO plays a protective role in neutrophil-endothelial interaction by preventing neutrophil adhesion and endothelial cell damage by activated neutrophils. NO suppresses neutrophil phagocytic activity but stimulates longdistance contact interactions through tubulovesicular extensions or cytonemes. Neutrophils are the main source of superoxide, but NO flow results in the formation of peroxynitrite, a compound with high biological activity. Peroxynitrite is involved in the regulation of eicosanoid biosynthesis and inhibits endothelial prostacyclin synthase. NO and peroxynitrite modulate cellular 5-lipoxygenase activity and leukotriene synthesis. Long-term exposure of neutrophils to NO results in the activation of cell death mechanisms and neutrophil apoptosis. Conclusion: Nitric oxide and the NO/superoxide interplay fine-tune mechanisms regulating life and death in neutrophils.

Background: Neuroinflammatory diseases that affect spinal cord or associated spinal nerves represent challenging conditions for management in current medicine because of their complex pathology, poor prognosis, and high morbidity, which strikingly reduces the quality of life of patients. In this sense, a better understanding of the cellular and molecular mechanisms of spinal cord neuroinflammation might contribute to the development of novel therapies. Oligodendrocytes have unique and vital biological properties in central nervous system (CNS) homeostasis and physiology. A growing body of experimental evidence demonstrates that these glial cells are involved in the pathophysiological mechanisms underlying many chronic, neurodegenerative, and incapacitating CNS disorders. These cells also have important implications for the development and maintenance of neural plasticity and chronic pain states. On the other hand, evidence indicates that oligodendrocytes and their products may act in favor of CNS promoting beneficial effects orchestrating CNS tissue repair after injury. Objective: The present review aims to explore the multi-faceted actions of spinal cord oligodendrocyte progenitors cells (OPCs) and mature oligodendrocytes in CNS inflammation and pathology, addressing their roles in experimental and clinical settings. A major focus was given to spinal cord amyotrophic lateral sclerosis, multiple sclerosis (MS)/experimental autoimmune encephalomyelitis (EAE), traumatic injury and pain processing. Methods: This review analyses and discusses published original research articles regarding the role of OPCs/oligodendrocytes in spinal cord inflammation and pain processing. Results and Conclusion: Findings from a number of clinical and experimental paradigms suggest spinal cord OPCs/oligodendrocytes are a potential therapeutic target for the control of neuroinflammation.

Tyrosine kinases are a subgroup of a large class of protein kinases that transfer phosphate groups from ATP to various amino acid residues. By phosphorylating the tyrosine residues, the tyrosine kinases are responsible for the activation of various proteins through signal transduction cascades, which serves as a ubiquitous mechanism of cell signaling. The frequent success of many tyrosine kinase inhibitors (TKIs) in clinical success and diseasecausing mutations in protein kinases suggests that a large number of kinases may represent therapeutically relevant targets. To date, most of the clinical and preclinical TKIs are ATPcompetitive non-covalent inhibitors, which achieve their selectivity by recognizing the unique features of specific protein kinases. Of growing interest now in the scientific community is the development of irreversible inhibitors that form covalent bonds with cysteines or other nucleophilic residues in the ATP binding pocket. Irreversible TKIs have many potential advantages including prolonged pharmacodynamics, reasonable compound design suitability, high potency, and the ability to validate pharmacological specificity by mutations in reactive cysteine residues. Here, we review recent efforts to develop cysteine-targeting irreversible TKIs and to discuss their patterns of configuration that identify adenosine triphosphate binding pockets and their biological activities.

Giving a glance to the report of Wound Care Market by Product updated in 2017, we can see that wound care market is expected to reach USD 22.01 billion by 2022 from USD 18.35 billion at a CAGR of 3.7%. Numerous factors are driving the growth of this market, including the increasing prevalence of chronic wounds and acute wounds, increasing aged population, rising R activities and advancement in the field of wound care research. Advanced wound management products are accounted for the largest market share in 2017. These evidences mean that the wound care research represents a Clinical Emergency other than an interesting Marketing tool. Drug therapies so far fight efficaciously with the opportunistic pathologies derived from chronic wounds, although an unsolved challenge is still finding a useful remedy to correct the impaired wound healing process and overcome the chronic wound state, to avoid bacterial rising and severe pain. Traditional medicinal plants have been widely used in the management of wounds and different plant extracts have been evaluated for their wound healing properties through both in vitro and in vivo studies. Their phytochemical components in particular quercetin, contribute to their remedial properties in wound repair. Quercetin has important biological activities related to the improvement of the wound healing process. The present review discusses and focuses on the latest findings of the wound healing properties of quercetin, alone or as a part of plant extract, and its role as a new frontier in wound repair.

tiRNAs & tRFs are a class of small molecular noncoding tRNA derived from precise processing of mature or precursor tRNAs. Most tiRNAs & tRFs described originate from nucleus-encoded tRNAs, and only a few tiRNAs and tRFs have been reported. They have been suggested to play important roles in inhibiting protein synthesis, regulating gene expression, priming viral reverse transcriptases, and the modulation of DNA damage responses. However, the regulatory mechanisms and potential function of tiRNAs & tRFs remain poorly understood. This review aims to describe tiRNAs & tRFs, including their structure, biological functions and subcellular localization. The regulatory roles of tiRNAs & tRFs in translation, neurodegeneration, metabolic diseases, viral infections, and carcinogenesis are also discussed in detail. Finally, the potential applications of these noncoding tRNAs as biomarkers and gene regulators in different diseases is also highlighted.

Glioblastoma Multiforme (GBM) is the most frequent glioma with a poor prognosis. The mainstay treatment for GBM is chemotherapy, but the average survival of GBM remains unsatisfactory due to therapeutic resistance. Poor permeability restricted by the Blood Brain Barrier (BBB) and the presence of Glioblastoma Stem Cells (GSCs) remain as two problems for chemotherapy. Recently, nanocarriers have attracted much attention in the research of GBM, owing to their advantages in self-assembly, biosafety, release controllability, and BBB penetrability, making them promising candidates for GBM treatment. This article aims to review the biologic signatures of BBB and GSCs, as well as the new development of nano-drug delivery systems to facilitate our understanding of targeted treatment for GBM.