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Background: Exosomes-a subset of extracellular vesicles (EVs)-are secreted by virtually all cells, including human neuroblastoma cancer (SH-SY5Y) cells, into bodily fluids. Oxidative stress is critically involved in exosome biogenesis and release. Silver nanoparticles (AgNPs) induce cytotoxicity, oxidative stress, and apoptosis in cancer and non-cancer cells. Methods: Here, we studied whether AgNPs-induced oxidative stress could enhance exosome biogenesis and release under low serum conditions in the presence of AgNPs. Although several studies have reported various mechanisms that contribute to EV biogenesis and release from cells, none exists on the involvement of external stimuli by controlling acetylcholinesterase (AChE) and neutralsphingomyelinase (n-SMase) activities, total protein concentration of exosomes, and exosome count. Results: Owing to cytotoxic and oxidative stresses, AgNPs-treated cells and exosome release were significantly facilitated, which strongly correlated with the AgNPs-induced oxidative stress. Moreover, the expression levels of some important exosome biomarkers were found to be significant under oxidative stress conditions. N-acetylcysteine prevented oxidative stress-induced exosome biogenesis and release. Furthermore, we identified the involvement of the ceramide pathway in exosome functions by inhibiting AChE and n-SMase activities, and exosome protein/counts. These data contribute to the understanding of how AgNPs and intracellular molecular pathways affect exosome biogenesis and release in SH-SY5Y cells. Conclusion: To the best of our knowledge, this is the first study showing that AgNPs stimulate exosome biogenesis and release by inducing oxidative stress and ceramide pathways.

Sangiliyandi Gurunathan,1 Min-Hee Kang,1 Muhammad Qasim,2 Khalid Khan,3 Jin-Hoi Kim1 1Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul, 05029, Korea; 2Center of Bioengineering and Nanomedicine, Department of Food Science, University of Otago, Dunedin, 9054, New Zealand; 3Science and Technology KPK, Peshawar, PakistanCorrespondence: Sangiliyandi Gurunathan; Jin-Hoi KimDepartment of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul, 05029, KoreaTel +82 2 450 3687Fax +82 2 544 4645Email gsangiliyandi@yahoo.com; jhkim541@konkuk.ac.krAbstract: Extracellular vesicles (EVs) are a heterogeneous group of membrane-limited vesicles and multi-signal messengers loaded with biomolecules. Exosomes and ectosomes are two different types of EVs generated by all cell types. Their formation depends on local microdomains assembled in endocytic membranes for exosomes and in the plasma membrane for ectosomes. Further, EV release is a fundamental process required for intercellular communication in both normal physiology and pathological conditions to transmit/exchange bioactive molecules to recipient cells and the extracellular environment. The unique structure and composition of EVs enable them to serve as natural nanocarriers, and their physicochemical properties and biological functions can be used to develop next-generation nano and precision medicine. Knowledge of the cellular processes that govern EVs biology and membrane trafficking is essential for their clinical applications. However, in this rapidly expanding field, much remains unknown regarding EV origin, biogenesis, cargo sorting, and secretion, as well as EV-based theranostic platform generation. Hence, we present a comprehensive overview of the recent advances in biogenesis, membrane trafficking, and functions of EVs, highlighting the impact of nanoparticles and oxidative stress on EVs biogenesis and release and finally emphasizing the role of EVs as nanotherapeutic agents.Keywords: extracellular vesicle, membrane trafficking, vesicle formation, cargo sorting and fusion, nanotherapeutics

Conventional tissue engineering, cell therapy, and current medical approaches were shown to be successful in reducing mortality rate and complications caused by cardiovascular diseases (CVDs). But still they have many limitations to fully manage CVDs due to complex composition of native myocardium and microvascularization. Fabrication of fully functional construct to replace infarcted area or regeneration of progenitor cells is important to address CVDs burden. Three-dimensional (3D) printed scaffolds and 3D bioprinting technique have potential to develop fully functional heart construct that can integrate with native tissues rapidly. In this review, we presented an overview of 3D printed approaches for cardiac tissue engineering, and advances in 3D bioprinting of cardiac construct and models. We also discussed role of immune modulation to promote tissue regeneration.

Sangiliyandi Gurunathan,1 Muhammad Qasim,2 Min-Hee Kang,1 Jin-Hoi Kim1 1Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul, 05029, Korea; 2Center of Bioengineering and Nanomedicine, Department of Food Science, University of Otago, Dunedin, 9054, New ZealandCorrespondence: Jin-Hoi KimDepartment of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul, 05029, KoreaTel +82 2 450 3687Fax +82 2 544 4645Email jhkim541@konkuk.ac.krAbstract: Cancer is a large group of diseases and the second leading cause of death worldwide. Lung, prostate, colorectal, stomach, and liver cancers are the most common types of cancer in men, whereas breast, colorectal, lung, cervical, and thyroid cancers are the most common among women. Presently, various treatment strategies, including surgical resection combined with chemotherapy, radiotherapy, nanotherapy, and immunotherapy, have been used as conventional treatments for patients with cancer. However, the clinical outcomes of advanced-stage disease remain relatively unfavorable owing to the emergence of chemoresistance, toxicity, and other undesired detrimental side effects. Therefore, new therapies to overcome these limitations are indispensable. Recently, there has been considerable evidence from experimental and clinical studies suggesting that melatonin can be used to prevent and treat cancer. Studies have confirmed that melatonin mitigates the pathogenesis of cancer by directly affecting carcinogenesis and indirectly disrupting the circadian cycle. Melatonin (MLT) is nontoxic and exhibits a range of beneficial effects against cancer via apoptotic, antiangiogenic, antiproliferative, and metastasis-inhibitory pathways. The combination of melatonin with conventional drugs improves the drug sensitivity of cancers, including solid and liquid tumors. In this manuscript, we will comprehensively review some of the cellular, animal, and human studies from the literature that provide evidence that melatonin has oncostatic and anticancer properties. Further, this comprehensive review compiles the available experimental and clinical data analyzing the history, epidemiology, risk factors, therapeutic effect, clinical significance, of melatonin alone or in combination with chemotherapeutic agents or radiotherapy, as well as the underlying molecular mechanisms of its anticancer effect against lung, breast, prostate, colorectal, skin, liver, cervical, and ovarian cancers. Nonetheless, in the interest of readership clarity and ease of reading, we have discussed the overall mechanism of the anticancer activity of melatonin against different types of cancer. We have ended this report with general conclusions and future perspectives.Keywords: melatonin receptors, antioxidant, antiangiogenic, anticancer, apoptosis, angiogenesis, metastasis, chemotherapy, combination therapy, molecular mechanisms

Sangiliyandi Gurunathan, Min-Hee Kang, Jin-Hoi Kim Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul, 05029, KoreaCorrespondence: Sangiliyandi Gurunathan; Jin-Hoi KimDepartment of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul, 05029, KoreaTel +82 2 450 3687Fax +82 2 544 4645Email gsangiliyandi@yahoo.com; jhkim541@konkuk.ac.krAbstract: Exosomes are nanoscale-sized membrane vesicles secreted by almost all cell types into the extracellular environment upon fusion of multivesicular bodies and plasma membrane. Biogenesis of exosomes is a protein quality control mechanism, and once released, exosomes transmit signals to other cells. The applications of exosomes have increased immensely in biomedical fields owing to their cell-specific cargos that facilitate intercellular communications with neighboring cells through the transfer of biologically active compounds. The diverse constituents of exosomes reflect their cell of origin and their detection in biological fluids represents a diagnostic marker for various diseases. Exosome research is expanding rapidly due to the potential for clinical application to therapeutics and diagnosis. However, several aspects of exosome biology remain elusive. To discover the use of exosomes in the biomedical applications, we must better understand the basic molecular mechanisms underlying their biogenesis and function. In this comprehensive review, we describe factors involved in exosomes biogenesis and the role of exosomes in intercellular signaling and cell-cell communications, immune responses, cellular homeostasis, autophagy, and infectious diseases. In addition, we discuss the role of exosomes as diagnostic markers, and their therapeutic and clinical implications. Furthermore, we addressed the challenges and outstanding developments in exosome research, and discuss future perspectives.Keywords: extracellular vesicle, exosome, biogenesis, function, cell-cell communication, immune response, cellular homeostasis, autophagy