Exploring the utility of extracellular vesicles in ameliorating viral infection-associated inflammation, cytokine storm and tissue damage

Pillalamarri, Nagavalli; Abdullah, Abdullah; Khan, Luqman; Ullah, Asad; Jonnakuti, Sriya; Ullah, Mujib

doi:10.1016/j.tranon.2021.101095

Cited by 26 publications

(27 citation statements)

References 134 publications

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“…The effects of human defense mechanisms like APOBEC on SARS-CoV-2 evolution have been studied extensively 46 , 50 , 52 , 55 - 57 . Based on these studies and the previously established role of AID in B cell tolerance and antibody maturation, we have shown in Figures 1 & 2 , a possible mechanism for the humoral immune response against SARS-CoV-2 infection 54 , 58 . We understand that the generation of high affinity antibodies in COVID-19 individual has far reaching consequences with regard to new therapeutic targets and vaccine design.…”

Section: Is Aid a Gateway To A Strong And Enduring Immune Response?supporting

confidence: 55%

Cytidine deamination-induced perpetual immunity to SAR-CoV-2 infection is a potential new therapeutic target

et al. 2021

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As the world is racing to develop perpetual immunity to the SARS-CoV-2 virus. The emergence of new viral strains, together with vaccination and reinfections, are all contributing to a long-term immunity against the deadly virus that has taken over the world since its introduction to humans in late December 2019. The discovery that more than 95 percent of people who recovered from COVID-19 had long-lasting immunity and that asymptomatic people have a different immune response to SARS-CoV-2 than symptomatic people has shifted attention to how our immune system initiates such diverse responses. These findings have provided reason to believe that SARS-CoV-2 days are numbered. Hundreds of research papers have been published on the causes of long-lasting immune responses and variations in the numbers of different immune cell types in COVID 19 survivors, but the main reason of these differences has still not been adequately identified. In this article, we focus on the activation-induced cytidine deaminase (AID), which initiates molecular processes that allow our immune system to generate antibodies against SARS-CoV-2. To establish lasting immunity to SARS-CoV-2, we suggest that AID could be the key to unlocking it.

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Section: Is Aid a Gateway To A Strong And Enduring Immune Response?supporting

confidence: 55%

Cytidine deamination-induced perpetual immunity to SAR-CoV-2 infection is a potential new therapeutic target

et al. 2021

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“…It will also be interesting to explore if HSP20 physically interacts with SIRT-1 to direct cell proliferation. HSP20 is a protein chaperone that facilitates the nuclear translocation of other proteins[ 38 ], while SIRT1 is primarily localized to the cytoplasm and can translocate to the nucleus upon activation[ 39 , 40 ]. Therefore, it is likely that HSP20 binds to SIRT1 and serves as a chaperone for its nuclear translocation, thereby creating a feed-forward loop that upregulates the expression of SIRT1 in stem cells.…”

Section: Discussionmentioning

confidence: 99%

Heat shock protein 20 promotes sirtuin 1-dependent cell proliferation in induced pluripotent stem cells

Ullah¹,

Pek²,

Yannarelli³

et al. 2021

WJSC

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BACKGROUND Heat shock proteins (HSPs) are molecular chaperones that protect cells against cellular stresses or injury. However, it has been increasingly recognized that they also play crucial roles in regulating fundamental cellular processes. HSP20 has been implicated in cell proliferation, but conflicting studies have shown that it can either promote or suppress proliferation. The underlying mechanisms by which HSP20 regulates cell proliferation and pluripotency remain unexplored. While the effect of HSP20 on cell proliferation has been recognized, its role in inducing pluripotency in human-induced pluripotent stem cells (iPSCs) has not been addressed. AIM To evaluate the efficacy of HSP20 overexpression in human iPSCs and evaluate the ability to promote cell proliferation. The purpose of this study was to investigate whether overexpression of HSP20 in iPSCs can increase pluripotency and regeneration. METHODS We used iPSCs, which retain their potential for cell proliferation. HSP20 overexpression effectively enhanced cell proliferation and pluripotency. Overexpression of HSP20 in iPSCs was characterized by immunocytochemistry staining and real-time polymerase chain reaction. We also used cell culture, cell counting, western blotting, and flow cytometry analyses to validate HSP20 overexpression and its mechanism. RESULTS This study demonstrated that overexpression of HSP20 can increase the pluripotency in iPSCs. Furthermore, by overexpressing HSP20 in iPSCs, we showed that HSP20 upregulated proliferation markers, induced pluripotent genes, and drove cell proliferation in a sirtuin 1 (SIRT1)-dependent manner. These data have practical applications in the field of stem cell-based therapies where the mass expansion of cells is needed to generate large quantities of stem cell-derived cells for transplantation purposes. CONCLUSION We found that the overexpression of HSP20 enhanced the proliferation of iPSCs in a SIRT1-dependent manner. Herein, we established the distinct crosstalk between HSP20 and SIRT1 in regulating cell proliferation and pluripotency. Our study provides novel insights into the mechanisms controlling cell proliferation that can potentially be exploited to improve the expansion and pluripotency of human iPSCs for cell transplantation therapies. These results suggest that iPSCs overexpressing HSP20 exert regenerative and proliferative effects and may have the potential to improve clinical outcomes.

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“…Microbubbles have the potential to protect their cargo from degradation, restrict the drug release to disease sites, and prevent nonspecific drug delivery to healthy tissues [ 69 , 70 ]. Medicine in bubbles enhances targeted drug delivery, tumor targeting, ultrasound imaging, and intracellular drug release [ 7 , 71 ].…”

Section: Discussionmentioning

confidence: 99%

Artificial intelligence and guidance of medicine in the bubble

et al. 2021

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Microbubbles are nanosized gas-filled bubbles. They are used in clinical diagnostics, in medical imaging, as contrast agents in ultrasound imaging, and as transporters for targeted drug delivery. They can also be used to treat thrombosis, neoplastic diseases, open arteries and vascular plaques and for localized transport of chemotherapies in cancer patients. Microbubbles can be filled with any type of therapeutics, cure agents, growth factors, extracellular vesicles, exosomes, miRNAs, and drugs. Microbubbles protect their cargo from immune attack because of their specialized encapsulated shell composed of lipid and protein. Filled with curative medicine, they could effectively circulate through the whole body safely and efficiently to reach the target area. The advanced bubble-based drug-delivery system, integrated with artificial intelligence for guidance, holds great promise for the targeted delivery of drugs and medicines.

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Exploring the utility of extracellular vesicles in ameliorating viral infection-associated inflammation, cytokine storm and tissue damage

Cited by 26 publications

References 134 publications

Cytidine deamination-induced perpetual immunity to SAR-CoV-2 infection is a potential new therapeutic target

Cytidine deamination-induced perpetual immunity to SAR-CoV-2 infection is a potential new therapeutic target

Heat shock protein 20 promotes sirtuin 1-dependent cell proliferation in induced pluripotent stem cells

Artificial intelligence and guidance of medicine in the bubble

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