Current Drug Targets - Volume 20, Issue 14, 2019

Infectious diseases, instigated by pathogenic microorganisms are the cause of numerous health problems in developing countries. Infectious diseases got a place in the list of top ten death causes worldwide. The reason behind that level of severity is antimicrobial resistance. Antimicrobial resistance makes the antimicrobial agents useless when used in the treatment of infectious diseases. Microbes have very smartly achieved resistance against synthetic and semi-synthetic antimicrobial agents for their survival. Therefore, the handling of these diseases has become challenging. The resistance developing power is the reason for their existence since a million years. Due to their highly dangerous nature, proper treatment of infectious diseases has become a topic of concern. This leads the scientists or researchers to focus their research towards natural agents. Plants synthesize secondary metabolites to cope up with biotic and abiotic changes in the environment. Alkaloids are one of the secondary metabolites, synthesized by plants. Alkaloids protect the plant from predators and help them to fight with pathogens. The protecting nature of alkaloids can be used as a strong weapon in battle with resistant microorganisms. The purpose of this review is to provide information about the antimicrobial activity of alkaloids obtained from different plants and their combination with synthetic antimicrobials. Their mechanism of action against microorganisms is also given in the review.

The Biopharmaceutical classification system (BCS) classifies the drugs based on their intrinsic solubility and intestinal permeability. The drugs with good solubility and intestinal permeability have good bioavailability. The drugs with poor solubility and poor permeability have solubility dependent and permeability dependent bioavailability, respectively. In the current pharmaceutical field, most of the drugs have poor solubility. To solve the problem of poor solubility, various solubility enhancement approaches have been successfully used. The effects of these solubility enhancing approaches on the intestinal permeability of the drugs are a matter of concern, and must not be overlooked. The current review article focuses on the effect of various solubility enhancing approaches viz. cyclodextrin, surfactant, cosolvent, hydrotropes, and amorphous solid dispersion, on the intestinal permeability of drugs. This article will help in the designing of the optimized formulations having balanced solubility enhancement without affecting the permeability of drugs.

Ovarian cancer (OC) is one of the most common cancers globally with a high rate of cancer- associated mortality. OC may be classified into epithelial cell neoplasms, germ cell neoplasms and stromal cell neoplasms. The five-year survival in the early and advanced stages of disease is approximately 90% and 15%, respectively. microRNAs are short, single-stranded, non-coding ribonucleic acid (RNA). miRNAs play critical roles in post transcriptionally regulations of gene expression. miRNAs are found in different tissues and body fluids. In carcinogenesis the expression of miRNAs are altered. Recent studies have revealed that there is a relationship between alteration of miRNAs expression and the prognosis of patients with OC. The aim of this review was to summarize the findings of recent studies that have investigated the expression of circulating and tissue miRNAs as novel biomarkers in the prognosis of OC.

Viral myocarditis is a cardiac disease caused by Group B Coxsackie virus of Enterovirus genus in the Picorna viridae family. It causes heart failure in children, young and adults. Ten Percent (10%) of acute heart failure and 12% of sudden deaths in young and adults who are less than 40 years is due to this viral myocarditis. If treatment action is not taken earlier, the viral disease can develop into chronic myocarditis and Dilated Cardiomyopathy which lead to congestive heart failure. And these eventually result in a reduced cardiac function which finally brings the victim to death. The only treatment option of the disease is heart transplantation once the acute stage of disease develops to chronic and Dilated Cardiomyopathy. Currently, there is a limitation in daily clinical treatments and even some available treatment options are ineffective. Therefore, focusing on search for treatment options through investigation is imperative. Recent studies have reported that biological molecules show a promising role. But their mechanism of pathogenesis is still unclear. A detailed study on identifying the role of biological molecules involved in Coxsackie B3 virus induced myocarditis and their mechanisms of pathogenesis; compiling and disseminating the findings of the investigation to the scientific communities contribute one step forward to the solution. Therefore, this review is aimed at compiling information from findings of current studies on the potential therapeutic role of micro RNA, cytokines and chemokines on the mechanism of pathogenesis of Coxsackie virus B3- induced myocarditis to give brief information for scholars to conduct a detailed study in the area.

High mobility group box-1 (HMGB1) mainly belongs to the non-histone DNA-binding protein. It has been studied as a nuclear protein that is present in eukaryotic cells. From the HMG family, HMGB1 protein has been focused particularly for its pivotal role in several pathologies. HMGB-1 is considered as an essential facilitator in diseases such as sepsis, collagen disease, atherosclerosis, cancers, arthritis, acute lung injury, epilepsy, myocardial infarction, and local and systemic inflammation. Modulation of HMGB1 levels in the human body provides a way in the management of these diseases. Various strategies, such as HMGB1-receptor antagonists, inhibitors of its signalling pathway, antibodies, RNA inhibitors, vagus nerve stimulation etc. have been used to inhibit expression, release or activity of HMGB1. This review encompasses the role of HMGB1 in various pathologies and discusses its therapeutic potential in these pathologies.

Colorectal cancer (CRC) is one of the most common cancers globally and is associated with a high rate of morbidity and mortality. A large proportion of patients with early stage CRC, who undergo conventional treatments develop local recurrence or distant metastasis and in this group of advanced disease, the survival rate is low. Furthermore there is often a poor response and/or toxicity associated with chemotherapy and chemo-resistance may limit continuing conventional treatment alone. Choosing novel and targeted therapeutic approaches based on clinicopathological and molecular features of tumors in combination with conventional therapeutic approach could be used to eradicate residual micrometastasis and therefore improve patient prognosis and also be used preventively. Peptide- based vaccination therapy is one class of cancer treatment that could be used to induce tumorspecific immune responses, through the recognition of specific antigen-derived peptides in tumor cells, and this has emerged as a promising anti-cancer therapeutic strategy. The aim of this review was to summarize the main findings of recent studies in exciting field of peptide-based vaccination therapy in CRC patients as a novel therapeutic approach in the treatment of CRC.

Background: The kidney and cardiovascular system are closely related to each other during the modulation of the cardiovascular homeostasis. However, the search for new alternatives for the treatment and diagnosis of cardiovascular diseases does not take into account this relationship, so their evaluation results and the advantages offered by their global and integrative analysis are wasted. For example, a variety of receptors that are overexpressed in both pathologies is large enough to allow expansion in the search for new molecular targets and ligands. Nanotechnology offers pharmacological targeting strategies to kidney, heart, and blood vessels for overcoming one of the essential restrictions of traditional cardiovascular therapies the ones related to their unspecific pharmacodynamics distribution in these critical organs. Recent Findings: Drug or contrast agent nano-targeting for treatment or diagnosis of atherosclerosis, thrombosis, renal cancer or fibrosis, glomerulonephritis, among other renal, cardiac and blood vessels pathologies would allow an increase in their efficacy and a reduction of their side effects. Such effects are possible because, through pharmacological targeting, the drug is mainly found at the desired site. Review Purpose: In this mini-review, active, passive, and physical targeting strategies of several nanocarriers that have been assessed and proposed for the treatment and diagnosis of different cardiovascular diseases, are being addressed.