Engineered Vesicles and Hydrogel Technologies for Myocardial Regeneration.

Increased prevalence of cardiovascular disease and potentially life-threatening complications of myocardial infarction (MI) has led to emerging therapeutic approaches focusing on myocardial regeneration and restoration of physiologic function following infarction. Extracellular vesicle (EV) technology has gained attention owing to the biological potential to modulate cellular immune responses and promote the repair of damaged tissue. Also, EVs are involved in local and distant cellular communication following damage and play an important role in initiating the repair process. Vesicles derived from stem cells and cardiomyocytes (CM) are of particular interest due to their ability to promote cell growth, proliferation, and angiogenesis following MI. Although a promising candidate for myocardial repair, EV technology is limited by the short retention time of vesicles and rapid elimination by the body. There have been several successful attempts to address this shortcoming, which includes hydrogel technology for the sustained bioavailability of EVs. This review discusses and summarizes current understanding regarding EV technology in the context of myocardial repair.

Hyperlipidemia in tendon injury: chronicles of low-density lipoproteins.

Hyperlipidemia impacts millions of people globally and has been the major risk factor for developing atherosclerosis and cardiovascular disease. Interestingly, hyperlipidemic subjects exhibit increased incidence of rotator cuff tendon injury (RCTI) and disorganization of tendon matrix. Low-density lipoproteins (LDL) and its oxidized form (ox-LDL) play a crucial role in hyperlipidemia-driven pro-inflammatory responses in multiple tissues including the tendon. The signaling of oxLDL upregulates the inflammatory cytokines, chemokines, adhesion molecules, and the activation of monocytes/macrophages/resident tendon cells and matrix metalloproteinases impairing the tendon homeostasis resulting in the alteration of extracellular matrix. In addition, the hyperlipidemia-driven immune response and subsequent oxidative stress promote degenerative responses in the tendon tissue. However, the pathological mechanisms underlying the occurrence of RCTI in hyperlipidemia and the effect of ox-LDL in tendon matrix are currently unknown. The present review focuses on the implications and perspectives of LDL/oxLDL on the increased incidence of RCTI.

Pathogenicity of Type I Interferons in Mycobacterium tuberculosis.

Tuberculosis (TB) is a leading cause of mortality due to infectious disease and rates have increased during the emergence of COVID-19, but many of the factors determining disease severity and progression remain unclear. Type I Interferons (IFNs) have diverse effector functions that regulate innate and adaptive immunity during infection with microorganisms. There is well-documented literature on type I IFNs providing host defense against viruses; however, in this review, we explore the growing body of work that indicates high levels of type I IFNs can have detrimental effects to a host fighting TB infection. We report findings that increased type I IFNs can affect alveolar macrophage and myeloid function, promote pathological neutrophil extracellular trap responses, inhibit production of protective prostaglandin 2, and promote cytosolic cyclic GMP synthase inflammation pathways, and discuss many other relevant findings.

Mycobacterium tuberculosis: Implications of Ageing on Infection and Maintaining Protection in the Elderly.

Several reports have suggested that ageing negatively affects the human body resulting in the alteration of various parameters important for sufficient immune health. Although, the breakdown of innate and adaptive immunity has been hypothesized to increase an individual's susceptibility to infections including Mycobacteria tuberculosis (M. tb), little research has been done to bridge this gap and understand the pathophysiology underlying how ageing increases the pathogenesis of M. tb infection. Our objective was to study research from a plethora of resources to better understand the pathogenesis of ageing and its link to the human immune system. To achieve this goal, this article explores how ageing decreases the collective T-cell immune response, reduces glutathione (GSH) production, over activates the mammalian target of rapamycin (mTORC1) pathway, inhibits autophagy and mitophagy, and alters various protective genes/transcription factors. Specifically highlighting how each of these pathways cripple an individual's immune system and increases their susceptibility from M. tb infection. Furthermore, research summarized in this article gives rise to an additional mechanism of susceptibility to M. tb infection which includes a potential defect in antigen presenting by dendritic cells rather than the T-cells response. Inflammaging has also been shown to play a role in the ageing of the immune system and can also potentially be a driving factor for increased susceptibility to M. tb infection in the elderly. In addition, this article features possible preventative strategies that could decrease infections like M. tb in this population. These strategies would need to be further explored and range from immunomodulators, like Everolimus to antioxidant supplementation through GSH intake. We have also proposed the need to research these therapies in conjunction with the administration of the BCG vaccine, especially in endemic populations, to better understand the risk contracting M. tb infection as well as ways to prevent infection in the first place.