Immunoengineered MXene nanosystem for mitigation of alloantigen presentation and prevention of transplant vasculopathy.

MXenes are an emerging class of nanomaterials with significant potential for applications in nanomedicine. Amongst MXene technologies, titanium carbide (Ti3C2Tx) nanomaterials are the most mature and have received significant attention to tackle longstanding clinical challenges due to its tailored physical and material properties. Cardiac allograft vasculopathy is an aggressive form of atherosclerosis and a major cause of mortality among patients with heart transplants. Blood vessel endothelial cells (ECs) stimulate alloreactive T-lymphocytes to result in sustained inflammation. Herein, we report the first application of Ti3C2Tx MXene nanosheets for prevention of allograft vasculopathy. MXene nanosheets interacted with human ECs and downregulated the expression of genes involved in alloantigen presentation, and consequently reduced the activation of allogeneic lymphocytes. RNA-Seq analysis of lymphocytes showed that treatment with MXene downregulated genes responsible for transplant-induced T-cell activation, cell-mediated rejection, and development of allograft vasculopathy. In an in vivo rat model of allograft vasculopathy, treatment with MXene reduced lymphocyte infiltration and preserved medial smooth muscle cell integrity within transplanted aortic allografts. These findings highlight the potential of Ti3C2Tx MXene in treatment of allograft vasculopathy and inflammatory diseases.

Oxidative stress-induced apoptosis and autophagy: Balancing the contrary forces in spermatogenesis.

Spermatogenesis is a complex process in the testis and is a cornerstone of male infertility. The abundance of unsaturated fatty acid and high cell division rate make male germs cells prone to DNA deterioration. ROS-mediated oxidative stress triggers DNA damage, autophagy, and apoptosis in male germ cells, which are critical causative factors that lead to male infertility. The complex connection and molecular crosstalk between apoptosis and autophagy is seen at multifaceted levels that interconnect the signaling pathways of these two processes. Multilevel interaction between apoptosis and autophagy is a seamless state of survival and death in response to various stressors. Interaction between multiple genes and proteins such as the mTor signaling pathway, Atg12 proteins, and the death adapter proteins, such as Beclin 1, p53, and Bcl-2 family proteins, validates such a link between these two phenomena. Testicular cells being epigenetically different from somatic cells, undergo numerous significant epigenetic transitions, and ROS modulates the epigenetic framework of mature sperm. Epigenetic deregulation of apoptosis and autophagy under oxidative stress conditions can cause sperm cell damage. The current review recapitulates the current role of prevailing stressors that generate oxidative stress leading to the induction of apoptosis and autophagy in the male reproductive system. Considering the pathophysiological consequences of ROS-mediated apoptosis and autophagy, a combinatorial approach, including apoptosis inhibition and autophagy activation, should be implemented as a therapeutic strategy to treat male idiopathic infertility. Understanding the crosslink between apoptosis and autophagy under stress conditions in male germ cells may play an essential role in developing therapeutic strategies to treat infertility.

The role of autophagy in the metabolism and differentiation of stem cells.

Autophagy is a very well-coordinated intracellular process that maintains cellular homeostasis under basal conditions by removing unnecessary or dysfunctional components through orderly degradation and recycling. Under pathological conditions, defects in autophagy have been linked to various human disorders, including neurodegenerative disorders and cancer. The role of autophagy in stem cell proliferation, differentiation, self-renewal, and senescence is well documented. Additionally, cancer stem cells (CSCs) play an important role in tumorigenesis, metastasis and tumor relapse and several studies have suggested the involvement of autophagy in the maintenance and invasiveness of CSCs. Hence, considering the modulation of autophagy in normal and cancer stems cells as a therapeutic approach can lead to the development or improvement of regenerative and anti-cancer therapies. Accordingly, modulation of autophagy can be regarded as a target for stem cell-based therapy of diseases with abnormal levels of autophagy. This article is focused on understanding the role of autophagy in stem cell homeostasis with an emphasis on the therapeutic potential of targeting autophagy for future therapies.