• International Journal of Stem Cells
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• v.16 no.3
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• pp.251-259
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• 2023

Mesenchymal stromal cells (MSCs) have attracted scientific and medical interest due to their self-renewing properties, pluripotency, and paracrine function. However, one of the main limitations to the clinical application of MSCs is their loss of efficacy after transplantation in vivo. Various bioengineering technologies to provide stem cell niche-like conditions have the potential to overcome this limitation. Here, focusing on the stem cell niche microenvironment, studies to maximize the immunomodulatory potential of MSCs by controlling biomechanical stimuli, including shear stress, hydrostatic pressure, stretch, and biophysical cues, such as extracellular matrix mimetic substrates, are discussed. The application of biomechanical forces or biophysical cues to the stem cell microenvironment will be beneficial for enhancing the immunomodulatory function of MSCs during cultivation and overcoming the current limitations of MSC therapy.

• East Asian mathematical journal
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• v.38 no.3
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• pp.357-363
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• 2022

Immunological imbalance eventually results in the development of various diseases. A typical example is an imbalance of cytokines with immunomodulatory abilities. In this paper, we propose a two-variable delay model to anti-pro-inflammatory cytokine therapy for autoimmune diseases, which are caused by an imbalance between the pro and anti-inflammatory cytokines. The interaction between pro- and anti-inflammatory cytokines were modeled mathematically to investigate the relevance of cytokines in disease processes. The delay time was estimated to maintain the stability of a biologically important steady state. In particular, the effects of delay with anti-pro-inflammatory cytokines therapy in autoinflammatory diseases were studied.

• Journal of Pharmacopuncture
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• v.23 no.2
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• pp.62-70
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• 2020

Coronavirus disease-19 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS CoV-2). Currently, the management of patients with COVID-19 depends mainly on repurposed drugs which include chloroquine, hydroxychloroquine, lopinavir/ritonavir, ribavirin, remdesivir, favipiravir, umifenovir, interferon-α, interferon-β and others. In this review, the potential of Nigella sativa (black cumin seeds) to treat the patients with COVID-19 analyzed, as it has shown to possess antiviral, antioxidant, anti-inflammatory, anticoagulant, immunomodulatory, bronchodilatory, antihistaminic, antitussive, antipyretic and analgesic activities. Medline/PubMed Central/PubMed, Google Scholar, Science Direct, Directory of open access journals (DOAJ) and reference lists were searched to identify articles associated with antiviral and other properties of N.sativa related to the signs and symptoms of COVID-19. Various randomized controlled trials, pilot studies, case reports and in vitro and in vivo studies confirmed that N.sativa has antiviral, antioxidant, anti-inflammatory, immunomodulatory, bronchodilatory, antihistaminic, antitussive activities related to causative oraganism and signs and symptoms of COVID-19. N. sativa could be used as an adjuvant therapy along with repurposed conventional drugs to manage the patients with COVID-19.

• BMB Reports
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• v.43 no.4
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• pp.250-256
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• 2010

Natural phosphodiester bond CpG-DNA that contains immunomodulatory CpG motifs (PO-DNA) upregulates the expression of proinflammatory cytokines and induces an Ag-driven Th1 response in a CG sequence-dependent manner in mice. In humans, only phosphorothioate backbone-modified CpG-DNA (PS-DNA) and not PO-DNA has immunomodulatory activity. In this study, we found that liposome-encapsulated PO-DNA upregulated the expression of human $\beta$-defensin-2 (hBD-2) and major histocompatibility class II molecules (HLA-DRA) in a CG sequence-dependent and liposome- dependent manner in human B cells. Of the three different liposomes, DOTAP has the unique ability to enhance the immunomodulatory activity of PO-DNA. In contrast, HLA-DRA and hBD-2 promoter activation can be induced by liposome-encapsulated PS-DNA in a CG sequence-independent manner, depending on the CpG-DNA species. Our observations demonstrate that, when encapsulated with a proper liposome in the immune system, natural PO-DNA has the potential to be a useful therapy for the regulation of the innate immune response.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.1 no.1
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• pp.79-89
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• 1998

Purpose: Though many antiviral or immunomodulatory agents have been used in patients with chronic HBV hepatitis, interferon is considered to be the only effective therapeutic agent so far. Among immunomodulatory agents, thymodulin, the oral form of thymosin, is currently in clinical trial. We compared the efficacy of alfa-interferon therapy alone with a combined therapy of alfa-interferon and thymodulin in children with chronic active hepatitis B. Method: Twenty three children aged 4.4~13.7 years who were known to be positive for HBsAg and HBeAg in serum for at least 6 months and who had biopsy-proven chronic active hepatitis were given either combined therapy of alfa-interferon and thymodulin or alfa-interferon alone, and all children were HBV DNA positive in their serum at the beginning. Follow-ups have been done for at least 1 year after a 6 month course of therapy and clearance of viral replication markers has been evaluated. Results: 1) During follow up period, 11 (48%) children were seroconverted to anti-HBe and were cleared of HBV DNA from their serum. However, 2 of them relapsed after discontinuance of interferon therapy. 2) Seroconversion occurred more frequently among those who had not been vertically transmitted, had elevated serum ALT levels and low HBV DNA levels before interferon therapy. 3) There was no significant advantage of the combined therapy with thymodulin compared to interferon therapy alone. Conclusion: Combined therapy of alfa-interferon and thymodulin failed to demonstrate synergistic effect. We think that combination therapies of alfa-interferon with other antiviral or immunomodulatory agents need to be studied in order to achieve better therapeutic responses.

• Food Science and Biotechnology
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• v.18 no.6
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• pp.1316-1321
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• 2009

Multiple beneficial properties of Opuntia ficus indica (OPF) are well established. In the present study, we have investigated the immunological role of OPF extract (OPFE) on murine splenocytes. OPFE dose- and time-dependently enhanced the proliferation of splenocytes without cytotoxicity. Our results also showed that the number of $CD4^+$ helper T cells and CD45R/$B220^+$ pan B cells increased markedly, but not $CD8^+$ cytotoxic T cells or $CD11b^+$ granulocytes/macrophages. In addition, OPFE significantly decreased the production levels of T helper (Th) 1 type cytokines, interferon (IFN)-$\gamma$, and tumor necrosis factor (TNF)-$\alpha$, although had no significantly differences in those of interleukin (IL)-4, a Th2 type cytokine in concanavalin A (Con A)-stimulated blastogenic cells. Furthermore, OPFE alone strongly increased IL-4 production and decreased TNF-$\alpha$ production even in the absence of Con A. On the basis of these results, this study suggests that OPFE enhances immunity by regulating the pro- and anti-inflammatory response, indicating that this extract exerts a marked immunomodulatory effect, confirming its usefulness as therapy for immune-related diseases.

• Korean Circulation Journal
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• v.53 no.12
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• pp.795-810
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• 2023

Background and Objectives: Myocarditis is a potentially fatal disease, but curative treatments have not yet been established. Myocardial inflammation is an important pathogenesis of this disease, and immunosuppressants such as methylprednisolone and immunoglobulin have been used for treatment; however, the effectiveness needs to be improved. Thalidomide and dipeptidyl peptidase (DPP) 4 inhibitors were recently investigated regarding their immunomodulatory properties. This study aimed to test whether thalidomide or a DPP4 inhibitor (evogliptin) can improve the effectiveness of myocarditis treatment using a rat model of experimental autoimmune myocarditis (EAM). Methods: Rats with or without myocarditis were administered thalidomide at 100 mg/kg/day and DPP4 inhibitor at 10 mg/kg/day orally. Measurement of echocardiography, serum inflammatory cytokines, myocardial histopathological examination, and immunohistochemical staining for leukocytes, macrophages, CD4+ T cells, and cytoskeleton were performed after 3 weeks, and the fibrosis area was measured after 3 and 6 weeks. Results: Thalidomide and DPP4 inhibitor did not reduce the severity of myocarditis compared with the EAM without treatment rats by comparing the echocardiographic data, myocardial CD4⁺, macrophages, neutrophil infiltrations, and the heart weight/body weight ratio in 3 weeks. The levels of inflammatory cytokines were not lower in the thalidomide and DPP4 inhibitor-treated group than in the untreated group in 3 weeks. In 6 weeks, thalidomide and DPP4 inhibitors did not reduce the fibrosis area compared to untreated groups. Conclusions: Although thalidomide and the DPP4 inhibitor had an immunomodulatory effect and are used against inflammatory diseases, they did not ameliorate myocardial inflammation and fibrosis in this rat model of EAM.

• Preventive Nutrition and Food Science
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• v.11 no.4
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• pp.268-272
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• 2006

Cimicifugae Rhizoma (CR) belongs to the Ranunculaceae family, which has been traditionally used to treat climacteric complaints, antipyretics and diaphoresis as an alternative medicine for estrogen hormone replacement therapy with estrogens. Recently, it has been reported that different extract fractions of CR have various effects such as anti-allergic, anti-inflammatory and anti-proliferative activities. The current study investigated the immunomodulatory effects of Cimicifugae Rhizoma water extracts (CRE) in the macrophage-like cell line, Raw 264.7. Our results showed that CRE ($1\sim50\;{\mu}g/mL$) stimulated tumoricidal activity and NO production, whereas phagocytic activity was inhibited at the same concentrations. Additionally, iNOS mRNA expression was significantly increased in Raw 264.7 exposed to CRE as demonstrated by RT-PCR. These results indicate that the tumoricidal activity induced by CRE may be mediated by the production of NO and these activities may be useful for the treatment of diseases such as cancer.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.47 no.2
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• pp.65-75
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• 2021

Medication-related osteonecrosis of the jaw (MRONJ) has recently associated to the increase in antiresorptive and anti-angiogenic drugs prescriptions in the treatment of oncologic and osteoporotic patients. The physiopathogenesis of MRONJ remains unclear and available treatments are unsatisfactory. Newer pharmacological treatments have shown good results, but are not curative and could have major side effects. At the same time as pharmacological treatments, mesenchymal stem cells (MSCs) have emerged as a promising therapeutic modality for tissue regeneration and repair. MSCs are multipotential non-hematopoietic progenitor cells capable to differentiating into multiple lineages of the mesenchyme. Bone marrow MSCs can differentiate into osteogenic cells and display immunological properties and secrete paracrine anti-inflammatory factors in damaged tissues. The immunomodulatory, reparative, and anti-inflammatory properties of bone marrow MSCs have been tested in a variety of animal models of MRONJ and applied in specific clinical settings. The aim of this review is to discuss critically the immunogenicity and immunomodulatory properties of MSCs, both in vitro and in vivo, the possible underlying mechanisms of their effects, and their potential clinical use as modulators of immune responses in MRONJ, and to identify clinical safety and recommendations for future research.

• Korean Journal of Clinical Laboratory Science
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• v.56 no.1
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• pp.1-9
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• 2024

Exosomes are nano-sized membrane-bound extracellular vesicles containing various biological molecules, such as nucleic acids, proteins, and lipids, which can be used to modulate physiological processes. The exosomal molecules secreted by cells can be extensively used as tools for diagnosis and therapy. Exosomes carry specific molecules released by the cells they originate from, which can be transferred to surrounding cells or tissues by the exosome. For these reasons, exosomes can be exploited as biomarkers for diagnosis, carriers for drug delivery, as well as therapeutics. In stem cell technology, exosomes have been an attractive option because they can be used as safer therapeutic agents for stem cell-based cell-free therapy. Recently, studies have demonstrated the safety and efficacy of mesenchymal stem cell-derived exosomes in alleviating symptoms associated with coronavirus disease 2019 as they have anti-inflammatory and immunomodulatory potential. Performing multiple studies on exosomes would provide innovative next-generation options for clinical diagnostics and therapy. This review summarizes the use of exosomes focusing on their diverse roles. In addition, the potential of exosomes is illustrated with a focus on how exosomes can be exploited as powerful tools in the days to come.