Search

Mesenchymal stem cells (MSCs) are a potential cell therapy candidate for autoimmune and inflammatory diseases due to their multilineage capacity and immune modulating function. MSCs exert immunomodulatory effects on target cells through the secretion of exosomes. Inflammatory conditions such as Toll-like receptors (TLRs) engagement can change the biological functions and immunomodulatory activities of MSCs and the contents of exosomes derived from MSCs are changed. Regulatory T-cells (Treg) are crucial for maintaining immune cell homeostasis and selftolerance. Our study aimed to investigate the impact of isolated exosomes from hWJ-MSCs that were treated with Poly (I:C) on regulatory CD4 CD25 Foxp3 T-cells. MSCs were harvested from human umbilical cord Wharton's Jelly by explant method. Stem cells were treated by Polyinosinic-polycytidylic acid sodium salt (Poly (I:C)) for 48 hours. Exosomes were extracted from supernatant of cells and Scanning electron microscopy (SEM) and Dynamic light scattering (DLS) were performed for them. Peripheral blood mononuclear cells (PBMCs) isolated from the healthy donors were stimulated with PHA (Phytohemagglutinin) and co-cultured with Poly (I:C) treated hWJ-MSCs derived exosome and untreated hWJ-MSCs derived exosome or without hWJ-MSCs-derived exosome for 6 days. Then, frequency of CD4+CD25+ Foxp3+ regulatory T cells was measured by flow cytometry. Our results showed that exosomes isolated from Poly (I:C) treated hWJ-MSCs significantly increased frequency of CD4+CD25+ Foxp3+ regulatory T cells compared to the untreated hWJMSCs derived exosome group and control group. Stimulation by TLR3 improved the anti-inflammatory features of exosomes that were derived from hWJ-MSCs by increasing the frequency of Treg cells. [ABSTRACT FROM AUTHOR]

Abstract Aims The clinical efficiency of dendritic cell (DC) therapy needs to be improved. Exosomes, as membrane nano-vesicles, carry bio-macromolecules and play essential roles in intercellular crosstalk. Here, it is proposed that tumor cell-derived exosomes could function as vehicles to deliver exogenous miRNA-155 into DCs, for simultaneous miRNA delivery and antigen priming of DCs. Following optimization of the miRNA-155 delivery, the effect of exogenous miRNA-155 overexpression on DCs is evaluated. Main methods For this purpose, exogenous miRNA-155 was electroporated with various voltages (0.100, 0.200, and 0.300 kV) into tumor cell-derived exosomes with various concentrations, and then DCs were treated with miRNA-155 loaded exosomes. To assess the effect of miRNA-155 loaded exosomes on DCs, the expression levels of IL12p70, IFN-γ, and IL10 in culture supernatants were measured by ELISA. Then, the expression profiles of DC surface markers, including CD11C, MHCII (I/A-I/E), CD86, CD40, and CD83 were investigated by flow cytometry. Key findings Concerning the results, exogenous miRNA-155 can be successfully inserted into tumor cell derived exosomes. Loading conditions for tumor cell-derived exosomes were enhanced for utilization as vehicles to deliver miRNA-155 into DCs. Analysis of the surface molecule revealed that miRNA-155 can increase the expression levels of MHCII (I/A-I/E), CD86, CD40, and CD83. ELISA analysis indicates that miRNA-155 can significantly increase, the levels of IL12p70, IFN-γ, and IL10. Significance Finally, it can be stated that miRNA-155 could be a candidate for dendritic cell maturation. This method can be applied in the modification of target cells in in vitro studies. [ABSTRACT FROM AUTHOR]

• Mesenchymal stem cell-derived exosomes are exciting nanocarriers with immunomoregulatory potential. • Allergen-loaded mesenchymal stem cell-derived exosomes could effectively ameliorate allergic inflammation through sublingual prophylaxis. This study evaluated the immunomodulatory and delivery potential of adipose tissue-isolated MSC-derived exosomes as a prophylactic regimen through a sublingual route in the ovalbumin (OVA)-induced allergic asthma murine model. Balb/c mice received 10 μg/dose of OVA-enriched MSC-derived exosomes as a prophylactic regimen in six doses during three weeks, and then OVA sensitization was conducted through intraperitoneal and aerosol administration of allergen. The total cells and eosinophils counted in nasal lavage fluid (NALF) and lung tissues were assessed for histopathological analysis. In addition, the secretion of IFN-γ, IL-4, and TGF-β by spleen cells and serum OVA-specific IgE levels were measured via ELISA. Significant reduction in the IgE levels and IL-4 production, along with elevated TGF-β levels, were observed. Also, limited cellular infiltrations and perivascular and peribronchiolar inflammation in the lung tissues and normal total numbers of cells and eosinophils in the NALF were reported. Prophylactic regimen using OVA-enriched MSC-derived exosomes modulated immune responses and inhibited allergic OVA sensitization. [ABSTRACT FROM AUTHOR]

Allergen-specific Immunotherapy (AIT) is the main therapeutic strategy to control and treat allergic disorders. Intranasal Immunotherapy (INIT) was introduced as a needle-free, noninvasive, and efficient approach among various routes of allergen administration. Since direct exposure of nasal mucosa to allergen extracts could induce local and systemic reactions, recent studies focus on establishing novel formulations using various delivery systems and adjuvants to improve INIT efficacy. This review categorizes and describes natural and synthetic micro/nanoparticles such as chitosan, PLGA, liposome, exosome, and nano-emulation droplets used as delivery systems or immunomodulatory and immune-regulatory agents. Also, multiple microbial agents, including probiotics, mycobacterial and viral components, TLR ligands, and biologic agents, i.e., antibody fragments, recombinant cytokines, vitamin A, and pulsed dendritic cells (DCs), are other platforms that are discussed. In addition, future perspectives and proposed strategies to help INIT were provided. [ABSTRACT FROM AUTHOR]

Tumor cells have various effects and dominance over other healthy cells. Cancer cells alter the cell program in healthy cells by secreting exosomes containing microRNAs involved in epithelial-mesenchymal transition (EMT). They can migrate to distant organs and establish a pre-metastatic niche. The purpose of this study was to determine the expression of miRNA-21–5p and miRNA-10b-5p, both of which are involved in EMT, in breast cancer-derived exosomes of various grades in order to identify new biomarkers involved in breast cancer progression. In this study, a blood sample was taken from 60 patients with grades I, II, or III breast cancer, as well as twenty healthy individuals as a control group. The exosomes were then purified from serum samples, and their relative expression of miRNA-21–5p and miRNA-10b-5p was determined using the real-time PCR method. miRNA-21–5p expression was significantly increased in patients with breast cancer grades I, II, and III compared to the control group (p < 0.01), (p < 0.0001) and (p < 0.0001), respectively, as was miRNA-10b-5p expression in patients with breast cancer grades I, II, and III compared to the control group (p < 0.0001), (p < 0.0001) and (p < 0.0001), respectively. Our results show that both microRNAs increase as cells lose their differentiation and become more invasive, which is evidence of cancer progression. Hence, both microRNAs may have the potential to be used alone or in combination with other biomarkers for the diagnosis and prognosis of breast cancer. • Increased expression of miRNA-21–5p and miRNA-10b-5p in serum-derived exosomes of breast cancer patients compared with healthy individuals. • Increased expression of miRNA-21–5p and miRNA-10b-5p effective in the epithelial-mesenchymal transition process in serum-derived exosomes of breast cancer patients in different grades. • miRNA-21–5p and miRNA-10b-5p are two new biomarkers in the diagnosis and monitoring of breast cancer. [ABSTRACT FROM AUTHOR]

Chemokines belong to the family of cytokines with chemoattractant properties that regulate chemotaxis and leukocyte migration, as well as the induction of angiogenesis and maintenance of hemostasis. Curcumin, the major component of the Curcuma longa rhizome, has various pharmacological actions, including anti-inflammatory, immune-regulatory, anti-oxidative, and lipid-modifying properties. Chemokines and chemokine receptors are influenced/modulated by curcumin. Thus, the current review focuses on the molecular mechanisms associated with curcumin's effects on chemoattractant cytokines, as well as putting into context the many studies that have reported curcumin-mediated regulatory effects on inflammatory conditions in the organs/systems of the body (e.g., the central nervous system, liver, and cardiovascular system). Curcumin's effects on viral and bacterial infections, cancer, and adverse pregnancy outcomes are also reviewed. [ABSTRACT FROM AUTHOR]

[Display omitted] • DC-based immunotherapy is one of the most widely used methods for cancer immunotherapy. • DC therapy with miR-155-enriched texosomes efficiently induced anti-tumor responses and significantly improved survival and inhibited tumor growth in the murine model of colorectal cancer. Nowadays, various strategies are considered to prime Dendritic cells (DCs) with tumor antigens. The tumor cell-derived exosomes are recognized as one of the most efficient strategies for achieving this purpose. In this regard, MicroRNA 155 (miR-155) is employed as one of the most prominent miRNAs, which play substantial roles in DCs maturation and IL-12 production. This study investigates the tumor growth suppression and antitumor effects of DCs primed with miR-155-enriched exosome on the BALB/c murine model of colorectal cancer induced by CT-26 cell lines. Therefore, a holistic framework is proposed for the analysis procedure. In the first stage, miRNA-155 was electroporated into texosomes. In the second stage, bone marrow-derived DCs were treated with miRNA-155 enriched texosomes. Then, antitumor properties of manipulated DC have been evaluated in the BALB/c mice model of colorectal cancer. After DC immunotherapy, several features have been assessed for each animal, including survival, body weight, tumor volume/size, histopathology, and serum cytokine levels. Also, flow cytometric evaluation has been performed for the spleen and the tumor tissue T-cell subsets. The findings demonstrated that the primed DCs could significantly increase IL-12p70 and IFN-γ in serum and accelerate the differentiation, proliferation, and cytotoxicity effects on the Th and CTL cells. Also, the treatment also increased the infiltration of Th and CTL cells into the tumor microenvironment while decreasing Tregs. This situation causes tumor growth control, and survival improvement. Therefore, DC immunotherapy with miR-155-enriched texosomes can be employed as a the desired approach for inducing antitumor immune responses, controlling tumor growth, and improving survival in mice with colorectal cancer. However, it is essential to perform more investigations to confirm the clinical application of this approach in humans and other types of tumors. [ABSTRACT FROM AUTHOR]

Background: Exosomes are nanoscale vesicles widely used as drug delivery systems. Mesenchymal stem cell (MSC)-derived exosomes have shown immunomodulatory potential. This study optimized loading OVA into the mice adipose tissue-derived MSC-isolated exosomes to prepare the OVA-MSC-exosome complex for allergen-specific immunotherapy. Methods: MSCs were harvested from mice adipose tissue and characterized by flow cytometry and evaluating differentiation potential. The exosomes were isolated and characterized via Dynamic Light Scattering, Scanning Electron Microscopy, and flow cytometry. Different concentrations of ovalbumin were incubated with MSC-exosome in various durations to optimize a more suitable protocol. BCA and HPLC analysis were used to quantify, and DLS was applied to qualify the prepared formulation of the OVA-exosome complex. Results: The harvested MSCs and isolated exosomes were characterized. Analysis of the OVAexosome complex revealed that OVA in primary 500 µg/ml concentration and incubation for 6 h results in higher efficacy. Conclusions: Loading OVA into MSC-derived exosomes was successfully optimized and could be administrated for allergen-specific immunotherapy in the animal model. [ABSTRACT FROM AUTHOR]

• F1 fraction of Mesobuthus eupeus scorpion venom successfully re-polarized murine peritoneal M2 macrophage toward M1 phenotype. • F1 fraction of Mesobuthus eupeus scorpion venom enhanced phagocytic capacity of macrophages. • Conditioned media of F1-treated macrophages suppressed migration and proliferation of CT-26 tumor cell line. Scorpion venoms identified as agents with anti-tumor and anti-angiogenic features. Tumor microenvironment (TME) plays a pivotal role in the process of tumorigenesis, tumor development, and polarization of M2 phenotype tumor associated macrophages (TAMs). M2 polarized cells are associated with tumor growth, invasion, and metastasis. The fractionation process was performed by gel filtration chromatography on a Sephadex G50 column. To elucidate whether scorpion venom can alter macrophage polarization, we treated interleukin (IL)-4-polarized M2 cells with isolated fractions from Mesobuthus eupeus. Next, we evaluated the cytokine production and specific markers expression for M2 and M1 phenotype using enzyme linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (PCR), respectively. The phagocytic capacity of macrophages was also assessed. In addition, the migration assay and MTT analysis were performed to investigate the effects of reprogrammed macrophages on the CT-26 colon cancer cells. The results indicated that F1 fraction of venom significantly upregulated the levels and expression of M1-associated cytokines and markers, including tumor necrosis factor-alpha (TNF-α) (p < 0.001), IL-1 (p < 0.01), interferon regulatory factor 5 (IRF5) (p < 0.0001), induced nitric oxide synthase (iNOS) (p < 0.0001), and CD86 (p < 0.0001), and downregulated M2-related markers, including transforming growth factor-beta (TGF-β) (p < 0.05), IL-10 (p < 0.05), Fizz1 (p < 0.0001), arginase-1 (Arg-1) (p < 0.0001), and CD206 (p < 0.001). The macrophage phagocytic capacity was enhanced after treatment with F1 fraction (p < 0.01). Moreover, incubation of CT-26 cell line with conditioned media of F1-treated macrophages suppressed migration (p < 0.0001) and proliferation (p < 0.01) of tumor cells. In conclusion, our findings demonstrated the potential of Mesobuthus eupeus venom in M2-to-M1 macrophage polarization as a promising therapeutic approach against proliferation and metastasis of colon cancer cells. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs), professional antigen-presenting cells that process and deliver antigens using MHC II/I molecules, can be enhanced in numerous ways. Exosomes derived from heat‐ shocked tumor cells (HS‐TEXs) contain high amounts of heat-shock proteins (HSPs). HSPs, as chaperons, can induce DC maturation. This study aimed to investigate whether HS‐TEXs can promote DC maturation. To generate DC, bone marrow-derived cells were treated with Interleukin-4 and GM-CSF. Exosomes were isolated from heat-treated CT-26 cells. The expression level of HSP in exosomes was checked by western blot and the increase in the expression of this protein was observed. Then, HS‐TEXs were co-cultured with iDCs to determine DC maturity, and then DCs were co-cultured with lymphocytes to determine DC activity. Our results showed that DCs treated with HS‐TEXs express high levels of molecules involved in DC maturation and function including MHCII, CD40, CD83, and CD86. HS‐TEXs caused phenotypic and functional maturation of DCs. In addition, flow cytometric results reflected a higher proliferative response of lymphocytes in the iDC / Tex + HSP group. HS‐TEXs could be used as a strategy to improve DC maturation and activation. [ABSTRACT FROM AUTHOR]

Increasing the efficacy of allergen-specific intranasal immunotherapy (INIT) has recently been the main goal of several studies to establish this route as a safe delivery method through mucosal pathways. In this case, the present study evaluated the potential of INIT using ovalbumin (OVA)- loaded mesenchymal stromal/stem cell (MSC)-derived exosomes (Exo-OVA) in an allergic asthma mouse model. Together with control groups, sensitized Balb/c mice underwent intranasal immunotherapy with Exo-OVA (10 µg OVA per dose) for three consecutive weeks. Serum-specific immunoglobulin E (IgE) levels, transforming growth factor-beta (TGF-ß), interleukin (IL)-4, and interferon-gamma (IFN-γ) production by cultured spleen cells, lung histopathologic analysis, and nasopharyngeal lavage fluid cellular examinations were then conducted. The results showed that INIT using Exo-OVA significantly increased IFN-γ and TGF-ß secretion, while allergen-specific IgE and IL-4 production were dramatically decreased compared to the control group receiving phosphate-buffered saline. In addition, the eosinophil and total cell counts in the nasopharyngeal lavage fluid were reduced, and inflammatory conditions and cell accumulation in lung tissue were ameliorated. In conclusion, the Exo-OVA improved the INIT efficacy compared to free OVA. Therefore, this formulation could be introduced as an effective approach for immunomodulatory purposes with a shorter treatment duration and reduced side effects. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs) orchestrate innate inflammatory responses and adaptive immunity through T‐cell activation via direct cell–cell interactions and/or cytokine production. Tolerogenic DCs (tolDCs) help maintain immunological tolerance through the induction of T‐cell unresponsiveness or apoptosis, and generation of regulatory T cells. Mesenchymal stromal cells (MSCs) are adult multipotent cells located within the stroma of bone marrow (BM), but they can be isolated from virtually all organs. Extracellular vesicles and exosomes are released from inflammatory cells and act as messengers enabling communication between cells. To investigate the effects of MSC‐derived exosomes on the induction of mouse tolDCs, murine adipose‐derived MSCs were isolated from C57BL/6 mice and exosomes isolated by ExoQuick‐TC kits. BM‐derived DCs (BMDCs) were prepared and cocultured with MSCs‐derived exosomes (100 μg/ml) for 72 hr. Mature BMDCs were derived by adding lipopolysaccharide (LPS; 0.1μg/ml) at Day 8 for 24 hr. The study groups were divided into (a) immature DC (iDC, Ctrl), (b) iDC + exosome (Exo), (c) iDC + LPS (LPS), and (d) iDC + exosome + LPS (EXO + LPS). Expression of CD11c, CD83, CD86, CD40, and MHCII on DCs was analyzed at Day 9. DC proliferation was assessed by coculture with carboxyfluorescein succinimidyl ester‐labeled BALB/C‐derived splenocytes p. Interleukin‐6 (IL‐6), IL‐10, and transforming growth factor‐β (TGF‐β) release were measured by enzyme‐linked immunosorbent assay. MSC‐derived exosomes decrease DC surface marker expression in cells treated with LPS, compared with control cells (≤.05). MSC‐derived exosomes decrease IL‐6 release but augment IL‐10 and TGF‐β release (p ≤.05). Lymphocyte proliferation was decreased (p ≤.05) in the presence of DCs treated with MSC‐derived exosomes. CMSC‐derived exosomes suppress the maturation of BMDCs, suggesting that they may be important modulators of DC‐induced immune responses. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer, a solid tumor with a high prevalence, contributes significantly to annual mortality rates. Various factors, including blood groups, may influence cancer risk. Multiple studies have suggested a potential connection between ABO and Rh blood groups and colorectal cancer risk. This study aims to investigate the role of ABO and Rh blood groups as risk factors in colorectal cancer patients. Materials and Methods: We conducted a retrospective study involving 71 colorectal cancer patients diagnosed between 2018 and 2020 in Khuzestan province, Iran, with known ABO blood types. Large-scale data from 29,922 blood donors in Khuzestan served as the healthy population control. The study analyzed the distribution of ABO blood groups among the blood donors. Results: Our findings revealed that the distribution of blood groups among colorectal cancer patients was as follows: O (31.0%), A (29.6%), B (29.6%), and AB (9.8%). However, our analysis did not establish a significant association between colorectal cancer risk and ABO antigens (P-value = 0.636) or Rh blood group (P = 0.198). Additionally, no significant differences in ABO blood types were observed concerning gender (P = 0.802), cancer type (P = 0.338), or tumor type (P = 0.207) among colorectal cancer patients. Conclusion: This study does not support a significant correlation between ABO and Rh blood groups and the risk of colorectal cancer, nor does it find associations with cancer type or tumor type. [ABSTRACT FROM AUTHOR]

• Sublingual immunotherapy is considered as a safe alternative for subcutaneous immunotherapy. • Mesenchymal stem cell-derived exosomes are interesting nanoparticle-based delivery systems with immunomodulatory potential. • Allergen-loaded mesenchymal stem cell-derived exosomes could effectively ameliorate allergic inflammation through sublingual immunotherapy. Allergen-specific sublingual immunotherapy (SLIT) was considered an interesting needle-free alternative for subcutaneous immunotherapy (SCIT). Mesenchymal stem cell (MSC)-derived exosomes were introduced as potent nanoscale delivery systems with immunomodulatory potentials. The current study investigated the therapeutic efficacy of SLIT using ovalbumin (OVA)-enriched MSC-derived exosomes formulation in a murine model of allergic asthma. MSCs were harvested from mice adipose tissues. Then, exosomes were isolated, and OVA-loaded exosomes were prepared. Following sensitization, Balb/c mice received therapeutic formulation (10 μg/dose OVA-containing MSC-derived exosomes) twice a week for two months. Serum OVA-specific IgE levels as well as IFN-γ, IL-4, and TGF-β secretions by cultured splenocytes were measured by ELISA. Also, lung tissue underwent histopathologic analysis, and the numbers of inflammatory cells and eosinophils in nasopharyngeal lavage fluid (NALF) were examined. SLIT using OVA-enriched exosomes significantly reduced IgE levels and IL-4 production, while the secretion of IFN-γ and TGF-β were significantly elevated. Also, a decrease was observed in the numbers of total cells and eosinophils in the NALF, and lower levels of perivascular and peribronchiolar inflammation and cellular infiltrations were observed in the lung tissue. SLIT using OVA-loaded exosomes improved immunomodulatory responses and efficiently alleviated allergic inflammation. [ABSTRACT FROM AUTHOR]

Background: Breast cancer and cervix cancer are the prevalent and deadly types of solid tumors around the world. According to the importance of cancer, it is necessary to understand predisposing factors that affect cancer risk. In this regard, previous studies suggest that blood types particularly ABO and Rh-Hr Blood-Group System could play roles in the risk and different features of cancers. In the present study, we aimed to evaluate the potential of ABO and Rh blood groups as risk factors for breast cancer and cervix cancer. Materials and Methods: A retrospective study included 109 and 14 patients diagnosed with breast cancer and cervix cancer, respectively with known ABO and Rh blood types, between 2018 and 2020 in Khuzestan province, Iran. For compression of ABO blood groups distribution between the cancer patients group and the healthy population, we used data from a large-scale study that report the distribution of ABO blood groups in 29,922 blood donors in Khuzestan province. Results: Based on obtained results the most frequent blood group is O followed by B, A, and AB in breast cancer and followed by A, B, and AB in cervix cancer. Results showed no significant association between ABO and Rh and the risk of breast and cervix cancer. Moreover, there is no relationship between blood types and clinic pathological features of breast cancer. Conclusion: Based on our data, ABO and in this regard, previous studies suggest that blood types particularly ABO and Rh-Hr Blood-Group System could play roles in the risk and different features of cancers. In the present study, we aimed to evaluate the potential of ABO and Rh blood groups as risk factors for breast cancer and cervix cancer do have not any association with the risk of breast and cervix cancer and their characteristics. [ABSTRACT FROM AUTHOR]

Objective: Seminal plasma (SP) contains large numbers of sub-cellular structures called extracellular vesicles (EV) which have been postulated to have immunological functions due to their bioactive contents including proteins and small non-coding RNAs. Although the response of endometrial cells to seminal EV (SEV) is recently being elucidated, the impact of these signaling vesicles on stroma-immune crosstalk is still unknown. Herein, we aimed to investigate the effect of conditioned medium (CM) derived from SEV-exposed endometrial stromal cells (eSC) on cytokine secretion by macrophages.Study Design: SEV were isolated from SP samples of healthy donors and characterized by common methods needed for EV characterization, including size determination by dynamic light scattering (DLS), transmission electron microscopy (TEM), and western blot analysis of EV markers. Endometrial biopsies were obtained from healthy individuals and eSC were isolated and characterized. EV internalization assay was performed by labeling the SEV with PKH67 green fluorescent dye. Then, the eSC were exposed to SEV and the CM was collected. Finally, the CM from SEV-exposed eSC was added to the macrophage culture and the level of inflammatory (interleukin (IL)-1α and IL-6) and anti-inflammatory (IL-10) cytokines were measured in the culture supernatant of macrophages.Results: The results demonstrated that the CM derived from SEV-exposed eSC induce IL-1α and IL-6 secretion by the macrophages, while the secretion of IL-10 was reduced.Conclusion: Our results support the idea that the stroma-immune interaction is affected by SEV. This effect may be a part of immunoregulatory function of SP inside upper female genital tract and have an obvious impact during peri-implantation period. [ABSTRACT FROM AUTHOR]

Early-stage gastrointestinal (GI) carcinomas are amenable malignancies, however, due to late diagnosis or lack of proper medication, alternative treatment necessitates new approaches such as dendritic cell (DC) therapy. Our previous microarray study indicated Lymphocyte antigen-6 (LY6E) as a commonly overexpressed biomarker in three lethal GI cancers, colon, gastric, and pancreatic. Therefore, we examined the antigenic potency of LY6E in stimulating DCs to elicit tumor-specific responses against human colorectal cancer (CRC) and gastric cancer (GC) cell lines HT-29 and AGS, respectively. LY6E peptide-pulsed DCs stimulated lymphocytes up to 55.9% in comparison with mature DCs (48.3%). Also, flow cytometry analysis of lymphocyte proliferation illustrated that the populations CD4+ and CD8+ were increased after treating by peptide-pulsed DCs (62.9% and 48.7% respectively). Furthermore, the cytotoxicity assay demonstrated that the 40:1 ratio of stimulated lymphocytes on AGS and HT29 cell lines was 65.1% and 66.2%, respectively. The research exposed that LY6E loaded DCs had substantial impact stimulation, proliferation, and lineage differentiation of lymphocytes. Besides, co-cultured of primed lymphocytes with AGS and HT29 cell lines exhibited cytotoxic activity. These data suggest LY6E as a potential candidate in developing DC therapy against CRC and AGS. [ABSTRACT FROM AUTHOR]

In this study, we evaluated the effects of nanofiber and film polymers with doxycycline for treating a wound in a diabetic rat model. 108 male rats were divided into six groups, the control group, the diabetic control, and the groups were diabetic rats receiving different wound dressing. At the 3rd, 7th, and 14th days, macroscopic/histologic imaging and tissue sampling were performed. Tissues were analyzed for IL-1β, TNF-α, IL-10, TIMP-1, and MMP-2 by using ELISA. Dressings of chitosan, polyvinyl alcohol, and doxycycline increased the rate of wound closure, the volume of collagen, dermal, and epidermis. In addition, it increased the number of fibroblasts and basal cell epidermis cells, vascular length, and decreased the number of neutrophil cells. Inflammatory cytokines and MMP-2 were decreased, and anti-inflammatory IL-10 and TIMP-1 were increased. It was ultimately attained that the combination of chitosan/ polyvinyl alcohol /doxycycline could be a useful dressing for the healing of diabetic wounds. [ABSTRACT FROM AUTHOR]

Background: Keloid and hypertrophic scars (HTS) are formed by excessive collagen formation. Angiotensin II, through the AT1 receptor, plays an important role in extracellular matrix production. However, less is known about angiotensin II and AT1 receptor concentrations in HTS and keloid tissues. Objective: The purpose of this study was to determine the angiotensin II and AT1 receptor concentrations in keloid, HTS, and normal skin tissues. Methods: Skin biopsy samples from patients with HTS (n=26), keloid (n=20), and normal (n=30) skin tissues were evaluated for angiotensin II and AT1 receptor concentrations by use of the enzyme-linked immunosorbent assay technique. Results: The angiotensin II concentration in patients with HTS was higher than that in the normal (P<0.0067) and keloid (P>0.9553) groups, while the AT1 receptor concentration in patients with keloid was higher than that in the HTS (P<0.0001) and normal (P<0.0048) groups. Conclusion: Angiotensin II and AT1 receptor concentrations could stimulate the formation of HTS and keloid. Angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors may be suitable compounds for the treatment of scar tissue. [ABSTRACT FROM AUTHOR]

• Tregitope can be used as a factor in regulating and unifying the immune response to the immunodominant allergen-derived T -cell epitope in the peptide immunotherapy. • Gene-based immunotherapy using Tregitope and immunodominant allergen-derived T -cell epitope can be a new method in the treatment of allergic diseases. • Immunotherapy using Tregitope and immunodominant T -cell epitope leads to the induction of a tollergenic response and possibly the development of allergen-specific regulatory T cells. Peptide-based immunotherapy (PIT) was introduced as an attractive approach in allergen-specific immunotherapy (AIT). However, PIT clinical trials have shown variable results, and immune response to peptides is not precisely predictable. On the other hand, induction of antigen-specific tolerance may be augmented when allergens are combined with the regulatory T cell epitope (Tregitope). This study aimed to evaluate the therapeutic administration of a plasmid DNA encoding Tregitope and ovalbumin (OVA) immunodominant epitope in the murine model of allergy. Following the induction of allergic rhinitis by ovalbumin, vaccinated group received three doses of recombinant plasmid containing Signal peptide-Tregitope-OVA T cell epitope. After the final OVA challenge, clinical symptoms, histopathological changes, OVA-specific IgE level, and cytokine secretion pattern of spleen cells were examined. Our data are showing that AIT with the recombinant DNA vaccine significantly suppressed airway inflammation; reduced eosinophilic infiltration in the nasal mucosa; decreased expression level of IL-4 and IL-17 in spleen cells, while IFN-γ , IL-10 , and TGF-β expression were increased. Moreover, OVA-specific IgE levels were also decreased. These results suggest that Tregitope-immunodominant T cell epitope fusion can act as a safe and effective approach in DNA-based allergen-specific immunotherapy. [ABSTRACT FROM AUTHOR]

Background: Nutmeg, Myristica fragrans Houtt, has shown anti-inflammatory properties in some studies. At present experimental study, we evaluated the effect of seed extract of nutmeg on adjuvant-induced arthritis in rats in comparison with flunixin meglumine. Materials and Methods: Experimental study was done in six groups of Wistar rats (each group 8 rats) as following: Group 1 was kept as control under similar conditions to other groups. All other rats received complete Freund's adjuvant at dose 0.1 ml which injected under skin of foot. Group 2 was received vehicle (normal saline). Group 3 received flunixin intraperitonealy at dose of 2 mg/kg body weight of rats daily for 12 days. Group4 to 6 received extract of nutmeg at dose 100, 200 and 300 mg/kg intraperitonealy and daily for 12 days. Four rats in each group were anesthetized and blood collected for serum analysis on 12th day. The ankle joint prepared for histopathological examination. The remained rats were kept until 21th day. Levels of the cytokine TNF-a in serum was measured using ELISA kit. Results: The serum levels of TNF-a in the group 2 were significantly increased; while nutmeg decreased the elevated TNF-a level in a dose-dependent manner but significantly with 300 mg/kg. The flunixin did not significantly decrease the levels of TNF-a. Nutmeg treated rats manifested pathological events in the ankle joints to a markedly lesser degree. Flunixin prevented pannus formation but it was ineffective in other lesions. Conclusion: Thus, nutmeg protected the joints against cartilage destruction and bone erosion in a dose-dependent manner. [ABSTRACT FROM AUTHOR]

Considering the global increase in the prevalence of hepatic fibrosis and ineffective disease treatment, novel therapies are urgently needed. The current study is focused on comparing the therapeutic effects of mesenchymal stem cells (MSC)/imatinib combination therapy to single (MSCs or imatinib) therapy, in a rat model of carbon tetrachloride (CCL4)-induced liver fibrosis. Using rats, hepatic fibrosis was induced by injection of CCL4. Rats were divided into 5 groups: CCL4-induced hepatic fibrosis, phosphate buffered saline (PBS) treatment (vehicle control), Bone marrow-MSCs (BM_MSCs), imatinib, and bone marrow-MSCs/imatinib co-treatment. The therapeutic impact of these approaches was determined using histopathology, sirius-red staining, serum markers, and qRT-PCR for over expression of matrix components. IHC and Western blot were conducted for further confirmation of the results. Single treatment with MSCs or imatinib and the combination therapy, all significantly reduced serum levels of ALT, AST, and ALP concomitant with down-regulation of α-SMA, pro-collagen I, pro-collagen III, collagen IV, and laminin. A significant reduction of ECM components deposits and a decrease in α-SMA expression were detected in all treatment groups. Pathological observations demonstrated that 20% and 40% of the rats in the MSC and MSC/imatinib group were in grade F0 respectively, while 80% of the rats of the imatinib group were in grade 2. Even though all treatment strategies studied resulted in an equally potent reduction in the mRNA and protein expression levels of pro-fibrotic markers, in aspect of pathological observations, our results demonstrate the highest therapeutic potential of utilizing combination of BM-MSCs and imatinib. [ABSTRACT FROM AUTHOR]