Myofibroblasts: Function, Formation, and Scope of Molecular Therapies for Skin Fibrosis

Myofibroblasts are contractile, α-smooth muscle actin-positive cells with multiple roles in pathophysiological processes. Myofibroblasts mediate wound contractions, but their persistent presence in tissues is central to driving fibrosis, making them attractive cell targets for the development of therapeutic treatments. However, due to shared cellular markers with several other phenotypes, the specific targeting of myofibroblasts has long presented a scientific and clinical challenge. In recent years, myofibroblasts have drawn much attention among scientific research communities from multiple disciplines and specialisations. As further research uncovers the characterisations of myofibroblast formation, function, and regulation, the realisation of novel interventional routes for myofibroblasts within pathologies has emerged. The research community is approaching the means to finally target these cells, to prevent fibrosis, accelerate scarless wound healing, and attenuate associated disease-processes in clinical settings. This comprehensive review article describes the myofibroblast cell phenotype, their origins, and their diverse physiological and pathological functionality. Special attention has been given to mechanisms and molecular pathways governing myofibroblast differentiation, and updates in molecular interventions.

Molecular Mechanisms And Clinical Implications Of Multiple Forms Of Mitophagy In The Heart

Mitochondria, the primary ATP-producing organelles, are highly abundant in cardiomyocytes. Mitochondrial function readily deteriorates in the presence of stress and, thus, maintenance of mitochondrial quality is essential for sustaining pump function in the heart. Cardiomyocytes under stress attempt to maintain mitochondrial quality primarily through dynamic changes in their morphology, namely fission and fusion, degradation and biogenesis. Mitophagy, a mitochondria-specific form of autophagy, is a major mechanism of degradation. The level of mitophagy is altered in stress conditions, which, in turn, significantly affects mitochondrial function, cardiomyocyte survival and death and cardiac function. Thus, mitophagy has been emerging as a promising target for treatment of cardiac conditions. To develop specific interventions modulating the activity of mitophagy in the heart, understanding how mitochondria are degraded in a given condition is important. Increasing lines of evidence suggest that there are multiple mechanisms by which mitochondria are degraded through mitophagy in the heart. For example, in addition to the well-established mechanism commonly utilized by general autophagy, involving Atg7 and LC3, recent evidence suggests that an alternative mechanism, independent of Atg7 and LC3, also mediates mitophagy in the heart. Here we describe molecular mechanisms through which mitochondria are degraded in the heart and discuss their functional significance. We also discuss molecular interventions to modulate the activity of mitophagy and their potential applications for cardiac conditions.

Tuberculosis: An Update on Pathophysiology, Molecular Mechanisms of Drug Resistance, Newer Anti-TB Drugs, Treatment Regimens and Host-Di-rected Therapies

The human tuberculosis (TB) is primarily caused by Mycobacterium tuberculosis (Mtb) that inhabits inside and amidst immune cells of the host with adapted physiology to regulate interdependent cellular functions with intact pathogenic potential. The complexity of this disease is attributed to various factors such as the reactivation of latent TB form after prolonged persistence, disease progression specifically in immunocompromised patients, advent of multi- and extensively-drug resistant (MDR and XDR) Mtb strains, adverse effects of tailor-made regimens, and drug-drug interactions among anti-TB drugs and anti-HIV therapies. Thus there is a compelling demand for newer anti-TB drugs or regimens to overcome these obstacles. Considerable multifaceted transformations in the current TB methodologies and molecular interventions underpinning host-pathogen interactions and drug resistance mechanisms may assist to overcome the emerging drug re-sistance. Evidently, recent scientific and clinical advances have revolutionised the diagnosis, prevention and treatment of all forms of the disease. This review sheds light on the current understanding of the pathogenesis of TB disease, molecular mechanisms of drug-resistance, progress on the development of novel or repurposed anti-TB drugs and regimens, host-directed therapies, with particular emphasis on underlying knowledge gaps and prospective for futuristic TB control pro-grams.

Understanding the pathogen evolution and transmission prevention measures: Recent findings on molecular interventions towards COVID-19 therapeutics via hints from the past

The novel pandemic has spread over in 150 countries as of March 2020. Approximately 900,000 people have been infected so far (WHO). Preventive measures are been taken globally to contain the rapid spread of virus. Compared to 2002 SARS epidemic, COVID-19 is apparently less lethal but far more contagious as it spreads more easily among individuals. This review highlights ongoing progress in figuring out the structure of major proteins designing vaccines and therapeutics to combat COVID-19 while also concentrating on developing preventive steps to avoid the emerging infection of viruses.

Molecular Interventions towards Multiple Sclerosis Treatment

Multiple sclerosis (MS) is an autoimmune life-threatening disease, afflicting millions of people worldwide. Although the disease is non-curable, considerable therapeutic advances have been achieved through molecular immunotherapeutic approaches, such as peptides vaccination, administration of monoclonal antibodies, and immunogenic copolymers. The main aims of these therapeutic strategies are to shift the MS-related autoimmune response towards a non-inflammatory T helper 2 (Th2) cells response, inactivate or ameliorate cytotoxic autoreactive T cells, induce secretion of anti-inflammatory cytokines, and inhibit recruitment of autoreactive lymphocytes to the central nervous system (CNS). These approaches can efficiently treat autoimmune encephalomyelitis (EAE), an essential system to study MS in animals, but they can only partially inhibit disease progress in humans. Nevertheless, modern immunotherapeutic techniques remain the most promising tools for the development of safe MS treatments, specifically targeting the cellular factors that trigger the initiation of the disease.