Current Drug Targets - Volume 23, Issue 13, 2022

MicroRNAs (miRNAs) are non-coding RNAs involved in the modulation of various biological processes, and their dysregulation is greatly associated with cancer progression as miRNAs can act as either tumour suppressors or oncogenes, depending on their intended target, mechanism of actions, and expression levels. This review paper aims to shed light on the role of overexpressed miRNAs in cancer progression. Cancer cells are known to upregulate specific miRNAs to inhibit the expression of genes regulating the cell cycle, such as PTEN, FOXO1, SOX7, caspases, KLF4, TRIM8, and ZBTB4. Inhibition of these genes promotes cancer development and survival by inducing cell growth, migration, and invasion while evading apoptosis, which leads to poor cancer survival rates. Therefore, the potential of antisense miRNAs in treating cancer is also explored in this review. Antisense miRNAs are chemically modified oligonucleotides that can reverse the action of overexpressed miRNAs. Currently, the therapeutic potential of antisense miRNAs is being validated in both in vitro and in vivo models. Studies have shown that antisense miRNAs could slow down the progression of cancer while enhancing the action of conventional anticancer drugs. These findings provide hope for future oncologic care as this novel intervention is in the process of clinical translation.

Vitiligo is an acquired, chronic, and progressive depigmentation or hypopigmentation characterized by the destruction of melanocytes and the occurrence of white patches or macules in the skin, mucosal surface of eyes, and ears. Melanocytes are the melanin pigment-producing cells of the skin which are destroyed in pathological conditions called vitiligo. Approximately 0.5 - 2.0% of the population is suffering from vitiligo, and a higher prevalence rate of up to 8.8% has been reported in India. It is caused by various pathogenic factors like genetic predisposition, hyperimmune activation, increased oxidative stress, and alteration in neuropeptides level. Genetic research has revealed a multi- genetic inheritance that exhibits an overlap with other autoimmune disorders. However, melanocytes specific genes are also affected (such as DDR1, XBP1, NLRP1, PTPN22, COMT, FOXP3, ACE, APE, GSTP1, TLR, SOD, and CTLA-4). A number of therapeutic options are employed for the treatment of vitiligo. The topical corticosteroids and immunomodulators are currently in practice for the management of vitiligo. Phototherapies alone and in combinations with other approaches are used in those patients who do not respond to the topical treatment. The main focus of this review is on the etiopathological factors, pharmacological management (phototherapy, topical, systemic, and surgical therapy), and herbal drugs used to treat vitiligo.

Significant endeavors can be made to develop effective drug delivery systems. Nowadays, many of these novel systems have gained attention as they focus primarily on increasing the bioavailability and bioaccessibility of several drugs to finally minimize the side effects, thus improving the treatment's efficacy. Microfluidics systems are unquestionably a superior technology, which is currently revolutionizing the current chemical and biological studies, providing diminutive chip-scale devices that offer precise dosage, target-precise delivery, and controlled release. Microfluidic systems have emerged as a promising delivery vehicle owing to their potential for defined handling and transporting of small liquid quantities. The latest microfabrication developments have been made for application to several biological systems. Here, we review the fundamentals of microfluidics and their application for local drug delivery.

Homeopathy is a widely practiced alternate system of medicine around the world that employs small doses of various medicines to promote auto-regulation and self-healing. It is among the most commonly used alternative approaches in cancer and other diseases and alternative therapeutic systems. It is widely used as palliative and as supportive therapy in cancer patients. Few cases have been reported on patients using homeopathy after surgery, radiotherapy, and chemotherapy, generally for overcoming side effects. The dose of Homoeopathic medicines and their mechanism of action in cancer has also been documented, while clinical trials on the effects of Homoeopathy in cancer treatment are rare. It is found that the anticancer potential of homeopathic medicines is reported for different cancer types, which show their efficacy through apoptosis and immune system modulation. Homeopathic treatment is an add-on to conventional therapy, with almost no interaction with the conventional drugs due to the small dose, and is largely attributed to improving lives by providing symptomatic relief, increasing survival time and boosting patient immunity. This review explores the accountability of the homeopathic system of medicine by highlighting some of the most commonly used homeopathic drugs for different types of cancers.

Lung toxicity is a key limiting factor for cancer therapy, especially lung, breast, and esophageal malignancies. Radiotherapy for chest and breast malignancies can cause lung injury. However, systemic cancer therapy with chemotherapy may also induce lung pneumonitis and fibrosis. Radiotherapy produces reactive oxygen species (ROS) directly via interacting with water molecules within cells. However, radiation and other therapy modalities may induce the endogenous generation of ROS and nitric oxide (NO) by immune cells and some nonimmune cells such as fibroblasts and endothelial cells. There are several ROS generating enzymes within lung tissue. NADPH Oxidase enzymes, cyclooxygenase-2 (COX-2), dual oxidases (DUOX1 and DUOX2), and the cellular respiratory system in the mitochondria are the main sources of ROS production following exposure of the lung to anticancer agents. Furthermore, inducible nitric oxide synthase (iNOS) has a key role in the generation of NO following radiotherapy or chemotherapy. Continuous generation of ROS and NO by endothelial cells, fibroblasts, macrophages, and lymphocytes causes apoptosis, necrosis, and senescence, which lead to the release of inflammatory and pro-fibrosis cytokines. This review discusses the cellular and molecular mechanisms of redox-induced lung injury following cancer therapy and proposes some targets and perspectives to alleviate lung toxicity.

Covid-19 may be associated with various neurological disorders, including dysautonomia, a dysfunction of the autonomic nervous system (ANS). In Covid-19, hypoxia, immunoinflammatory abnormality, and deregulation of the renin-angiotensin system (RAS) may increase sympathetic discharge with dysautonomia development. Direct SARS-CoV-2 cytopathic effects and associated inflammatory reaction may lead to neuroinflammation, affecting different parts of the central nervous system (CNS), including the autonomic center in the hypothalamus, causing dysautonomia. High circulating AngII, hypoxia, oxidative stress, high pro-inflammatory cytokines, and emotional stress can also provoke autonomic deregulation and high sympathetic outflow with the development of the sympathetic storm. During SARS-CoV-2 infection with neuro-invasion, GABA-ergic neurons and nicotinic acetylcholine receptor (nAChR) are inhibited in the hypothalamic pre-sympathetic neurons leading to sympathetic storm and dysautonomia. Different therapeutic modalities are applied to treat SARS-CoV-2 infection, like antiviral and anti-inflammatory drugs. Ivermectin (IVM) is a robust repurposed drug widely used to prevent and manage mild-moderate Covid-19. IVM activates both GABA-ergic neurons and nAChRs to mitigate SARS-CoV-2 infection- induced dysautonomia. Therefore, in this brief report, we try to identify the potential role of IVM in managing Covid-19-induced dysautonomia.