From seaweed to healing: the potential of fucoidan in wound therapy.

This bibliometric review examines the current state of research on fucoidan, a sulphated polysaccharide found in brown seaweed species, and its potential for wound healing. The review included 58 studies that investigated fucoidan's effects on wound healing, revealing that it possesses anti-inflammatory and antioxidant properties that could aid in the healing process. Fucoidan was also found to promote cell proliferation, migration, and angiogenesis, essential for wound healing. However, the optimal dosage, treatment duration, safety, and efficacy of fucoidan in various wound types and patient populations still require further investigation. Additionally, advanced wound dressings like hydrogels have garnered significant attention for their potential in wound healing. While this review indicates promise for fucoidan as a natural wound healing compound, it underscores the need for additional clinical trials to determine its optimal use as a commercial therapeutic agent in wound healing.

Influence of the isolation method on characteristics and functional activity of mesenchymal stromal cell-derived extracellular vesicles.

BACKGROUND AIMS: Extracellular vesicle (EV) isolation methods are based on different physicochemical properties and may result in the purification of distinct EV populations. We compared two different isolation methods suitable for producing clinical-grade mesenchymal stromal cell-derived EVs (MSC-EVs)-ion exchange chromatography (IEX) and ultrafiltration (UF)-and evaluated their impact on the composition and functional properties of EVs. METHODS: EVs were purified from conditioned culture medium using an anion exchange resin (IEX) or Amicon filters with a 100-kDa cutoff (UF) (MilliporeSigma, Burlington, MA, USA). We assessed nanoparticle size and distribution by nanoparticle tracking analysis (NTA) and tunable resistive pulse sensing (TRPS) and morphology by transmission electron microscopy. We also measured protein, lipid and total RNA concentration and immunophenotyped both EV populations by flow cytometry (MACSPlex assay; Miltenyi Biotec, Bergisch Gladbach, Germany). Moreover, immunomodulatory activity was tested using a standardized macrophage polarization assay and T-cell stimulation assay. Finally, proteomic analysis and cytokine quantification were carried out to better characterize both EV populations. RESULTS: We found by both TRPS and NTA that IEX and UF yielded a comparable amount of total particles with similar size and distribution. In addition, a similar quantity of lipids was obtained with the two procedures. However, IEX yielded 10-fold higher RNA quantity and a larger amount of proteins than UF. MSC-EVs isolated from IEX and UF were positive for the exosome markers CD9, CD63 and CD81 and showed a comparable surface marker expression pattern. Both populations demonstrated immunomodulatory activity in vitro, as they prevented acquisition of the M1 phenotype in lipopolysaccharide-stimulated macrophages and inhibited acquisition of the activation markers CD69 and CD25 on T cells, but the IEX-EVs exerted a significantly greater immunomodulatory effect on both macrophages and T cells compared with UF-EVs. Proteomic analysis and gene ontology enrichment analysis revealed no major differences between the preparations. Finally, cytokine quantification revealed that IEX-EVs were more enriched in some crucial anti-inflammatory and immunomodulatory cytokines (e.g., IL-2, IL-10, transforming growth factor beta and vascular endothelial growth factor) compared with UF-EVs. CONCLUSIONS: MSC-EVs isolated by IEX and UF displayed similar physicochemical, phenotypic and functional characteristics. In our conditions, both EV populations demonstrated important anti-inflammatory activity in macrophages and T cells. However, IEX-EVs were more potent than UF-EVs, which may indicate the superiority of this method for the production of clinical-grade EVs.

Role of CD9 Sensing, AI, and Exosomes in Cellular Communication of Cancer.

Exosomes are small membrane-bound vesicles that are released by various types of cells, including cancer cells, and play a role in intercellular communication. CD9 is a protein that is involved in cell signaling and adhesion. It is found on the surface of various cells, including cancer cells, and has been implicated in the communication between cancer cells and their microenvironment. Exosomes are small membrane-bound vesicles that are released by cells and contain various bioactive molecules, such as proteins, lipids, and nucleic acids. Exosomes have been shown to play a role in intercellular communication, and they have been implicated in the progression of cancer. There is evidence to suggest that CD9 is involved in the packaging and release of exosomes by cancer cells. CD9 has been shown to be important for the formation of tetraspanin-enriched microdomains (TEMs) on the surface of exosomes. These TEMs are thought to be important for the sorting and packaging of specific molecules into exosomes. In summary, CD9 appears to play an important role in the communication between cancer cells and their microenvironment via exosomes. The precise mechanisms by which CD9 mediates this communication are still being investigated, but the involvement of CD9 in exosome packaging and uptake suggests that it may be a promising target for the development of novel cancer therapies. Furthermore, CD9 has been shown to be involved in the uptake of exosomes by recipient cells. For example, studies have shown that CD9-positive exosomes released by cancer cells can be taken up by other cancer cells, leading to the transfer of oncogenic molecules and the promotion of cancer progression.

The current trend of exosome in epithelial ovarian cancer studies: A bibliometric review.

Background: Epithelial ovarian cancer (EOC) is the most common type of ovarian cancer. About 90% of ovary tumors are epithelial. The current treatment for EOC involves surgical debulking of the tumors followed by a combination of chemotherapy. While most patients achieve complete remission, many EOCs will recur and develop chemoresistance. The cancer cells can adapt to several stress stimuli, becoming resistant. Therefore, new ways to fight resistant cells during the disease are being studied. Recently, exosomes, which reflect cell behavior in normal and pathological conditions such as epithelial ovarian cancer, are of academic interest as new biomarkers for diagnosis and therapy. Consequently, the current study aimed to investigate the research output of exosomes in EOC. Method: A bibliometric method was used for analyzing publications on exosome and epithelial ovarian cancer from the beginning to 15 October 2022 by searching keywords in Scopus, PubMed and Google scholar. Annual scientific publications, authors, citations, journals, co-authorships, and keywords co-occurrence were analyzed and plotted using Microsoft Office Excel and VOS viewer. 39 original journal articles and 3 reviews have been published since 2015 up to 15 October 2022. Results: The findings showed that China is the top country in research output, international collaborations, organization, author, and sponsorship. The top journals were the Journal of Ovarian Research, Oncotarget, and Tumor Biology, all in the United States. The top institution was Shanghai Jiao Tong University in China. The top author was Xipeng Wang. Co-occurrence analysis showed that academics' interest is toward:1) 1) Exosomes as prognostic biomarkers of EOC as well as their role in the proliferation and migration of cells. 2) The role of exosomes in metastasis through different mechanisms; 3) The role of exosomes in epithelial-mesenchymal transition of ovarian cancer cells; 4) The diagnostic role of EVs in EOC; and 5) Conferring chemoresistance in EOC through the exosomal transfer of miRNAs. Conclusion: Research on the exosome and EOC has an increasing trend, and China is much more involved than other countries in research, financial support, and international cooperation. These findings could aid researcher in understanding novel ideas and subjects interested by sponsors in this field.

Exosome engineering for efficient and targeted drug delivery: Current status and future perspective.

Exosomes are membrane-bound vesicles that are released by most cells. They carry nucleic acids, cytokines, growth factors, proteins, lipids, and metabolites. They are responsible for inter- and intracellular communications and their role in drug delivery is well defined. Exosomes have great potential for therapeutic applications, but the clinical use is restricted because of limitations in standardized procedures for isolation, purification, and drug delivery. Bioengineering of exosomes could be one approach to achieve standardization and reproducible isolation for clinical use. Exosomes are important transporters for targeted drug delivery because of their small size, stable structure, non-immunogenicity, and non-toxic nature, as well as their ability to carry a wide variety of compounds. These features of exosomes can be enhanced further by bioengineering. In this review, possible exosome bioengineering approaches, their biomedical applications, and targeted drug delivery are discussed.

Different Sourced Extracellular Vesicles and Their Potential Applications in Clinical Treatments.

Extracellular vesicles (EVs) include a heterogeneous group of natural cell-derived nanostructures that are increasingly regarded as promising biotherapeutic agents and drug delivery vehicles in human medicine. Desirable intrinsic properties of EVs including the ability to bypass natural membranous barriers and to deliver their unique biomolecular cargo to specific cell populations position them as fiercely competitive alternatives for currently available cell therapies and artificial drug delivery platforms. EVs with distinct characteristics can be released from various cell types into the extracellular environment as a means of transmitting bioactive components and altering the status of the target cell. Despite the existence of a large number of preclinical studies confirming the therapeutic efficacy of different originated EVs for treating several pathological conditions, in this review, we first provide a brief overview of EV biophysical properties with an emphasis on their intrinsic therapeutic benefits over cell-based therapies and synthetic delivery systems. Next, we describe in detail different EVs derived from distinct cell sources, compare their advantages and disadvantages, and recapitulate their therapeutic effects on various human disorders to highlight the progress made in harnessing EVs for clinical applications. Finally, knowledge gaps and concrete hurdles that currently hinder the clinical translation of EV therapies are debated with a futuristic perspective.

Methodologies to Isolate and Purify Clinical Grade Extracellular Vesicles for Medical Applications.

The use of extracellular vesicles (EV) in nano drug delivery has been demonstrated in many previous studies. In this study, we discuss the sources of extracellular vesicles, including plant, salivary and urinary sources which are easily available but less sought after compared with blood and tissue. Extensive research in the past decade has established that the breadth of EV applications is wide. However, the efforts on standardizing the isolation and purification methods have not brought us to a point that can match the potential of extracellular vesicles for clinical use. The standardization can open doors for many researchers and clinicians alike to experiment with the proposed clinical uses with lesser concerns regarding untraceable side effects. It can make it easier to identify the mechanism of therapeutic benefits and to track the mechanism of any unforeseen effects observed.

Recent advances of SIRT1 and implications in chemotherapeutics resistance in cancer.

Cancer is a big group of diseases and one of the leading causes of mortality worldwide. Despite enormous studies and efforts are being carried out in understanding the cancer and developing drugs against tumorigenesis, drug resistance is the main obstacle in cancer treatments. Chemotherapeutic treatment is an important part of cancer treatment and drug resistance is getting gradually multidimensional with the advancement of studies in cancer. The underlying mechanisms of drug resistance are largely unknown. Sirtuin1 (SIRT1) is a type of the Class III histone deacetylase family that is distinctively dependent on nicotinamide adenine dinucleotide (NAD+) for catalysis reaction. SIRT1 is a molecule which upon upregulation directly influences tumor progression, metastasis, tumor cell apoptosis, autophagy, DNA repair, as well as other interlinked tumorigenesis mechanism. It is involved in drug metabolism, apoptosis, DNA damage, DNA repair, and autophagy, which are key hallmarks of drug resistance and may contribute to multidrug resistance. Thus, understanding the role of SIRT1 in drug resistance could be important. This study focuses on the SIRT1 based mechanisms that might be a potential underlying approach in the development of cancer drug resistance and could be a potential target for drug development.

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

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.

Diagnostic and Therapeutic Potential of Extracellular Vesicles.

Extracellular vesicles (EVs) are naturally phospholipid enclosed nanovesicles released by many cells in the body. They are stable in circulation, have low immunogenicity, and act as carriers for functionally active biological molecules. They interact with target organs and bind to the receptors. Their target specificity is important to use EVs as noninvasive diagnostic and prognostic tools. EVs play a vital role in normal physiology and cellular communication. They are known to protect their cargo from degradation, which makes them important drug carriers for targeted drug delivery. Using EVs with markers and tracking their path in systemic circulation can be revolutionary in using them as diagnostic tools. We will discuss the scope of this in this paper. Although there are limitations in EVs isolation and storage, their high biocompatibility will fuel more innovations to overcome these challenges.

SAR-CoV-2 infection, emerging new variants and the role of activation induced cytidine deaminase (AID) in lasting immunity.

As the world faces a fourth COVID-19 spike, scientists are learning a lot more about the new SARS-CoV-2 strains that were previously unknown. Currently, the Delta versions of SARS-CoV-2 have become the prevalent strains in much of the world since it first appeared in India in late 2020. Researchers believe they have discovered why Delta has been so successful: those infected with it create significantly more virus than those infected with the original strain of SARS-CoV-2, making it extremely contagious. This has redirected the focus to how our immune system defends us from these various pathogens and initiates such varied responses. Hundreds of research papers have been published on the origins of long-lasting immune responses and disparities in the numbers of different immune cell types in COVID 19 survivors, but the primary architect of these discrepancies has yet to be discovered. In this essay, we will concentrate on the primary architect protein, activation induced cytidine deaminase (AID), which triggers molecular processes that allow our immune system to produce powerful antibodies and SARS-CoV-2 specific B cells, allowing us to outwit the virus. We believe that if we ever achieve permanent immunity to SARS-CoV-2 infection, AID will be the key to releasing it.

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

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.

Artificial intelligence and guidance of medicine in the bubble.

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.

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

Extracellular vesicles (EVs) have emerged as potential mediators of intercellular communication. EVs are nano-sized, lipid membrane-bound vesicles that contains biological information in the form of proteins, metabolites and/or nucleic acids. EVs are key regulators of tissue repair mechanisms, such as in the context of lung injuries. Recent studies suggest that EVs have the ability to repair COVID19-associated acute lung damage. EVs hold great promise for therapeutic treatments, particularly in treating a potentially fatal autoimmune response and attenuate inflammation. They are known to boost lung immunity and are involved in the pathogenesis of various lung diseases, including viral infection. EV-based immunization technology has been proven to elicit robust immune responses in many models of infectious disease, including COVID-19. The field of EV research has tremendous potential in advancing our understanding about viral infection pathogenesis, and can be translated into anti-viral therapeutic strategies.

Microbubbles versus Extracellular Vesicles as Therapeutic Cargo for Targeting Drug Delivery.

Extracellular vesicles (EVs) and microbubbles are nanoparticles in drug-delivery systems that are both considered important for clinical translation. Current research has found that both microbubbles and EVs have the potential to be utilized as drug-delivery agents for therapeutic targets in various diseases. In combination with EVs, microbubbles are capable of delivering chemotherapeutic drugs to tumor sites and neighboring sites of damaged tissues. However, there are no standards to evaluate or to compare the benefits of EVs (natural carrier) versus microbubbles (synthetic carrier) as drug carriers. Both drug carriers are being investigated for release patterns and for pharmacokinetics; however, few researchers have focused on their targeted delivery or efficacy. In this Perspective, we compare EVs and microbubbles for a better understanding of their utility in terms of delivering drugs to their site of action and future clinical translation.