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1.
Mol Biol Rep ; 51(1): 394, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38446366

RESUMO

OBJECTIVE: Tumor suppressor candidate 2 has shown to be deleted in lung, colon, and bladder cancer types. In the present study, we aimed to investigate the expression of TUSC2 in breast cancer. MATERIALS AND METHODS: A total of thirty patients with breast cancer were included in the study. Normal and tumor tissue samples from fresh mastectomy materials were stored at -80 C until the number of cases was completed for gene expression analysis. Histopathological examination was carried out with routine hematoxylin & eosin method. TUSC2 staining was performed for immunohistochemical analysis. RESULTS: The tumors of thirteen patients were Luminal A, fourteen patients were Luminal B, one patient was cerbB2(+), and tumors of two patients were triple-negative. Ki67 proliferation index was less than 14% in fifteen cases and tumor size was less than 2 cm in seven cases. Lymphovascular invasion and lymph node metastasis were present in thirteen cases. Statistically, TUSC2 expression significantly decreased or was lost in breast tumor tissues compared to normal tissues (p < 0.0001). TUSC2 expression decreased as the Ki67 proliferation index increased (p = 0.0003), and TUSC2 expression decreased as tumor size increased (p = 0.0483). The loss or decrease in the TUSC2 expression was significant as the tumor grade increased (p = 0.3740). Gene expression analysis correlated with immunohistochemistry results. CONCLUSION: The results of the present study demonstrated a decrease or loss of TUSC2 expression in breast cancer tissue compared to normal tissue. A correlation was found between TUSC2 expression and Ki67 proliferation index and tumor size.


Assuntos
Neoplasias da Mama , Neoplasias Mamárias Animais , Humanos , Animais , Feminino , Neoplasias da Mama/genética , Antígeno Ki-67/genética , Mastectomia , Genes Supressores de Tumor , Proteínas Supressoras de Tumor/genética
2.
Anticancer Agents Med Chem ; 24(5): 334-347, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38305389

RESUMO

BACKGROUND: Breast cancer is a common cancer with high mortality rates. Early diagnosis is crucial for reducing the prognosis and mortality rates. Therefore, the development of alternative treatment options is necessary. OBJECTIVE: This study aimed to investigate the inhibitory effect of N-acetyl-D-glucosamine (D-GlcNAc) on breast cancer using a machine learning method. The findings were further confirmed through assays on breast cancer cell lines. METHODS: MCF-7 and 4T1 cell lines (ATCC) were cultured in the presence and absence of varying concentrations of D-GlcNAc (0.5 mM, 1 mM, 2 mM, and 4 mM) for 72 hours. A xenograft mouse model for breast cancer was established by injecting 4T1 cells into mammary glands. D-GlcNAc (2 mM) was administered intraperitoneally to mice daily for 28 days, and histopathological effects were evaluated at pre-tumoral and post-tumoral stages. RESULTS: Treatment with 2 mM and 4 mM D-GlcNAc significantly decreased cell proliferation rates in MCF-7 and 4T1 cell lines and increased Fas expression. The number of apoptotic cells was significantly higher than untreated cell cultures (p < 0.01 - p < 0.0001). D-GlcNAc administration also considerably reduced tumour size, mitosis, and angiogenesis in the post-treatment group compared to the control breast cancer group (p < 0.01 - p < 0.0001). Additionally, molecular docking/dynamic analysis revealed a high binding affinity of D-GlcNAc to the marker protein HER2, which is involved in tumour progression and cell signalling. CONCLUSION: Our study demonstrated the positive effect of D-GlcNAc administration on breast cancer cells, leading to increased apoptosis and Fas expression in the malignant phenotype. The binding affinity of D-GlcNAc to HER2 suggests a potential mechanism of action. These findings contribute to understanding D-GlcNAc as a potential anti-tumour agent for breast cancer treatment.


Assuntos
Neoplasias da Mama , Glucosamina , Camundongos , Humanos , Animais , Feminino , Acetilglucosamina/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Simulação de Acoplamento Molecular , Modelos Animais de Doenças
3.
Macromol Biosci ; 24(6): e2300352, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38284435

RESUMO

In this study, the anti-inflammatory effect of dental pulp mesenchymal stem cell (MSCs) exosomes loaded to mucoadhesive hydrogel is investigated in a dental nickel hypersensitivity murine model. After culture of dental pulp MSCs in the third passage MSCs are loaded to a mucoadhesive hydrogel based on chitosan, cross-linked with genipin and modified with catechol groups. A dental nickel hypersensitivity model is created by administering NiCl2 and 10 µg mL-1 lipopolysaccharide to 4-6 week-old Balb-c mice by intradermal injection. In mice treated with dental pulp MSC exosomes and exosomes in hydrogel, interferron gamma (IFN-γ) secreting CD4+T lymphocyte ratios significantly increase compared to the untreated group (p < 0.05). IFN-γ and interleukin 10 (IL-10) expression in buccal mucosa tissue sections and IFN-γ secreting CD4+T lymphocyte ratios are found to be significantly higher in mice treated with dental pulpa MSCs (DPMSCs) exosomes and DPMSCs exosomes in hydrogel compared to the untreated group (p < 0.05). According to flow cytometry results, IL-4 secreting CD4+T lymphocytes are found to be significantly decreased in DPMSCs exosomes group compared to dental nickel hypersensitivity group (p < 0.05). Administration of DPMSCs exosomes with mucoadhesive hydrogel may be an alternative to current medication in the treatment of dental nickel hypersensitivity.


Assuntos
Polpa Dentária , Exossomos , Hidrogéis , Células-Tronco Mesenquimais , Camundongos Endogâmicos BALB C , Níquel , Animais , Exossomos/metabolismo , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/citologia , Polpa Dentária/citologia , Polpa Dentária/metabolismo , Níquel/química , Hidrogéis/química , Hidrogéis/farmacologia , Camundongos , Anti-Inflamatórios/farmacologia , Interferon gama/metabolismo , Linfócitos T CD4-Positivos/imunologia , Interleucina-4/metabolismo
4.
Int J Pediatr Otorhinolaryngol ; 174: 111740, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37742461

RESUMO

OBJECT: Recurrent tonsillitis and tonsillar hypertrophy are two common diseases in children for which tonsillectomy is the definitive solution. The underlying causes of both diseases are not fully known. The aim of this study was to identify the predominant innate lymphoid cells in both diseases of the palatine tonsils, which are known to play an important role in the immune system. METHODS: Children who underwent tonsillectomy were divided into two groups as recurrent tonsillitis and tonsillar hypertrophy according to the indication for surgery. The proportions of innate lymphoid cell (ILC) groups and IFN-gamma, IL-10 and IL-17 secreting T lymphocyte cells were determined in tonsil and blood samples obtained during surgery. Local and peripheral immune responses were evaluated. Innate immune responses and acquired immune responses were compared. RESULTS: The results of our study showed that the proportions of the innate lymphoid cell 1 group (ILC1) were similar in tonsil tissue in patients with recurrent tonsillitis and tonsil hypertrophy, with no statistically significant difference. It was observed that the innate lymphoid cell 2 group (ILC2) was the predominant group in tonsil hypertrophy, the innate lymphoid cell 3 group (ILC3) was the predominant innate lymphoid cell group in recurrent tonsillitis, and the proportion of IL-17 secreting T lymphocytes in blood and tonsillar mononuclear cells was higher in recurrent tonsillitis patients than in tonsil hypertrophy patients. CONCLUSION: With the results obtained, the predominant innate lymphoid cells in the pathogenesis of both diseases were identified and local and peripheral responses were compared. These findings may be a guide for possible medical treatments for both diseases in the future.


Assuntos
Tonsilectomia , Tonsilite , Criança , Humanos , Tonsila Palatina/cirurgia , Tonsila Palatina/patologia , Imunidade Inata , Interleucina-17 , Linfócitos/patologia , Tonsilite/cirurgia , Tonsilite/patologia , Hipertrofia/cirurgia , Doença Crônica , Recidiva
5.
Tissue Cell ; 84: 102199, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37633122

RESUMO

AIM: The study aimed to evaluate the differentiation ability of intravitreally injected rat bone marrow-derived mesenchymal stem cells (rBM-MSCs) to retinal ganglion-like cells in a polystyrene microsphere induced rat glaucoma model. MATERIALS AND METHODS: The glaucoma rat model was generated via intracameral injection of 7 microliter polystyrene microspheres. Green fluorescence protein-labeled (GFP) rBM-MSCs were transplanted intravitreally at or after induction of ocular hypertension (OHT), depending on the groups. By the end of the fourth week, flat-mount retinal dissection was performed, and labeled against Brn3a, CD90, GFAP, CD11b, Vimentin, and localization of GFP positive rBM-MSCs was used for evaluation through immunofluorescence staining and to count differentiated retinal cells by flow cytometry. From 34 male Wistar albino rats, 56 eyes were investigated. RESULTS: Flow cytometry revealed significantly increased CD90 and Brn3a positive cells in glaucoma induced and with rBM-MSC injected groups compared to control(P = 0.006 and P = 0.003 respectively), sham-operated (P = 0.007 and P < 0.001 respectively), and only rBM-MSCs injected groups (P = 0.002 and P = 0.009 respectively). Immunofluorescence microscopy revealed differentiation of GFP labeled stem cells to various retinal cells, including ganglion-like cells. rBM-MSCs were observable in ganglion cells, inner and outer nuclear retinal layers in rBM-MSCs injected eyes. CONCLUSION: Intravitreally transplanted rBM-MSCs differentiated into retinal cells, including ganglion-like cells, which successfully created a glaucoma model damaged with polystyrene microspheres. Promisingly, MSCs may have a role in neuro-protection and neuro-regeneration treatment of glaucoma in the future.


Assuntos
Glaucoma , Células-Tronco Mesenquimais , Masculino , Ratos , Animais , Microesferas , Poliestirenos , Ratos Wistar , Glaucoma/induzido quimicamente , Glaucoma/terapia
6.
BMC Oral Health ; 23(1): 555, 2023 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-37568110

RESUMO

BACKGROUND: This in vitro study examined the effect of the inflammatory cytokines (tumour necrosis factor-α (TNF-α), interleukin (IL)-1ß, and IL-6) on osteogenic, chondrogenic, and adipogenic differentiation of dental pulp stem cells (DPSCs) which have significant relevance in future regenerative therapies. METHODS: DPSCs were isolated from the impacted third molar dental pulp and determined with flow cytometry analysis. DPSCs were divided into into 5 main groups with 3 subdivisions for each group making a total of 15 groups. Experimental groups were stimulated with TNF-α, IL-1ß, IL-6, and a combination of all three to undergo osteogenic, chondrogenic, and adipogenic differentiation protocols. Next, the differentiation of each group was examined with different staining procedures under a light microscope. Histological analysis of osteogenic, chondrogenic, and adipogenic differentiated pellets was assessed using a modified Bern score. Statistical significance determined using one-way analysis of variance, and correlations were assessed using Pearson's test (two-tailed). RESULTS: Stimulation with inflammatory cytokines significantly inhibited the osteogenic, chondrogenic and adipogenic differentiation of DPSCs in terms of matrix and cell formation resulting in weak staining than the unstimulated groups with inflammatory cytokines. On contrary, the unstimulated groups of MSCs have shown to be highly proliferative ability in terms of osteogenic, chondrogenic, and adipogenic differentiation. CONCLUSIONS: DPSCs have high osteogenic, chondrogenic, and adipogenic differentiation capabilities. Pretreatment with inflammatory cytokines decreases the differentiation ability in vitro, thus inhibiting tissue formation.


Assuntos
Interleucina-6 , Fator de Necrose Tumoral alfa , Humanos , Fator de Necrose Tumoral alfa/farmacologia , Polpa Dentária , Células-Tronco , Diferenciação Celular , Citocinas , Osteogênese , Células Cultivadas , Proliferação de Células
7.
PLoS One ; 17(5): e0266137, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35511824

RESUMO

OBJECTIVE: Dental mesenchymal stem cells (MSCs) are potential for use in tissue regeneration in inflammatory diseases due to their rapid proliferating, multilineage differentiation, and strong anti-inflammatory features. In the present study, immunoregulatory and glandular tissue regeneration effects of the dental follicle (DF)MSCs in Sjögren's Syndrome (SS) were investigated. METHODS: Dental follicle (DF) tissues were obtained from healthy individuals during tooth extraction, tissues were digested enzymatically and DFMSCs were cultured until the third passage. DFMSCs were labeled with Quantum dot 655 for cell tracking analysis. The induction of the SS mouse model was performed by the injection of Ro60-273-289 peptide intraperitoneally. DFMSCs were injected intraperitoneally, or into submandibular, or lacrimal glands. Splenocytes were analyzed for intracellular cytokine (IFN-γ, IL-17, IL-10) secretion in T helper cells, lymphocyte proliferation, and B lymphocyte subsets. Histologic analysis was done for submandibular and lacrimal glands with hematoxylin-eosin staining for morphologic examination. RESULTS: The systemic injection of DFMSCs significantly reduced intracellular IFN-γ and IL-17 secreting CD4+ T cells in splenocytes (p<0.05), and decreased inflammatory cell deposits and fibrosis in the glandular tissues. DFMSCs differentiated to glandular epithelial cells in submandibular and lacrimal injections with a significant reduction in lymphocytic foci. The results showed that few amounts of DFMSCs were deposited in glandular tissues when applied intraperitoneally, while high amounts of DFMSCs were located in glandular tissues and differentiated to glandular epithelial cells when applied locally in SS murine model. CONCLUSION: DFMSCs have the potential for the regulation of Th1, Th17, and Treg balance in SS, and ameliorate glandular dysfunction. DFMSCs can be a beneficial therapeutic application for SS.


Assuntos
Células-Tronco Mesenquimais , Síndrome de Sjogren , Animais , Saco Dentário/patologia , Modelos Animais de Doenças , Interleucina-17 , Células-Tronco Mesenquimais/patologia , Camundongos , Síndrome de Sjogren/patologia , Síndrome de Sjogren/terapia
8.
Nutr Clin Pract ; 37(3): 698-704, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34981863

RESUMO

BACKGROUND: Early detection of children at risk of developing malnutrition during hospitalization prevents the development of complications. This study aims to determine the malnutrition risk of pediatric inpatients by using three different nutrition screening tools and to evaluate the reliability/sensitivity of the screening tools. METHODS: This cross-sectional study included 176 children who were 1-16 years of age and were admitted to the pediatrics service of a second-line hospital. Body weight and height were used to evaluate the nutrition status of children. Age- and sex-specific z-score values for height for age (HFA), weight for age (WFA), and body mass index for age (BFA) were indicators of malnutrition. The Screening Tool for Risk of Impaired Nutritional Status and Growth (STRONGkids), Pediatric Yorkhill Malnutrition Score (PYMS), and Pediatric Nutrition Screening Tool (PNST) were used under the responsibility of pediatricians and dietitians to evaluate the risk of malnutrition in children. RESULTS: At admission, according to the HFA, BFA, and WFA SD scores (SDSs), the incidence of malnutrition in children was 8.5%, 14.8%, and 6.3%, respectively. Three screening tools determined that WFA SDSs were significantly higher in children without malnutrition risk than in those at risk of malnutrition (P < 0.05). PYMS revealed a relatively higher sensitivity of 90.9% and 84.6% for WFA and BFA, respectively, and PNST revealed a relatively higher sensitivity of 88.9% for HFA. CONCLUSIONS: PYMS and PNST are suitable for use in malnutrition risk assessment in pediatric inpatients because of the screening tools' high sensitivity.


Assuntos
Transtornos da Nutrição Infantil , Desnutrição , Pediatria , Criança , Transtornos da Nutrição Infantil/diagnóstico , Estudos Transversais , Feminino , Humanos , Pacientes Internados , Masculino , Desnutrição/diagnóstico , Desnutrição/epidemiologia , Desnutrição/etiologia , Programas de Rastreamento , Avaliação Nutricional , Estado Nutricional , Reprodutibilidade dos Testes , Fatores de Risco
9.
Immunotherapy ; 14(4): 225-247, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35012368

RESUMO

Background: In this article, the authors investigate the modulatory effects of dental mesenchymal stem cells (MSCs) on lymphocyte responses in primary Sjögren's syndrome (pSS), which is an autoimmune disease resulting from keratoconjunctivitis sicca and xerostomia. Methods: Mononuclear cells isolated from pSS patients cultured with or without dental MSCs and analyzed for lymphocyte responses via flow cytometry. Results: Dental-follicle (DF)- and dental-pulp (DP)-MSCs downregulated CD4+ T lymphocyte proliferation by increasing Fas-ligand expression on T lymphocytes and FoxP3 expressing Tregs, and decreasing intracellular IFN-γ and IL-17 secretion in pSS patients. DF-MSCs decreased the plasma B cell ratio in the favor of naive B cell population in pSS patients' mononuclear cells. Conclusion: DF- and DP-MSCs can be the new cellular therapeutic candidates for the regulation of immune responses in pSS.


Plain language summary In this article, the authors investigate the modulatory effects of dental mesenchymal stem cells (dental MSCs) on lymphocyte responses in primary Sjögren's syndrome (pSS), which is characterized by the infiltration of lymphocytes in exocrine glands. Lymphocyte proliferation, apoptosis, Tregs and total Bregs, intracellular cytokine secretion, total memory, plasma and naive B cell subsets were analyzed in pSS patients and compared them with healthy individuals. Dental follicle- and dental pulp-MSCs modulated CD4+ T lymphocyte responses in pSS patients' mononuclear cells by increasing Fas-ligand expression, enhancing FoxP3-expressing Tregs, and decreasing pro-inflammatory cytokine secretion. Our findings provide evidence for the potential role of dental-MSCs as a cellular therapy option in the treatment of pSS.


Assuntos
Linfócitos B/imunologia , Ativação Linfocitária/imunologia , Células-Tronco Mesenquimais/imunologia , Síndrome de Sjogren/imunologia , Linfócitos T/imunologia , Células Cultivadas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dente/imunologia
10.
Immunotherapy ; 13(10): 825-840, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33955241

RESUMO

Background: Atopic dermatitis (AD) is an inflammatory cutaneous disorder. The advancements in the understanding of AD immunological pathogenesis have caused the development of therapies that suppress the dysregulated immune response. We aimed to evaluate the immunomodulatory effect of dental stem cells (dental follicle-mesenchymal stem cells [DF-MSCs]) on AD patients. Materials & methods: We investigated the immunoregulatory potential of DF-MSCs on T cell response in AD and compared them with psoriasis and healthy individuals and the underlying mechanisms. Results: DF-MSCs significantly reduced Fas, FasL and TNFR II frequency in T cells, increased naive T cell population while reducing memory T cell, decreased inflammatory cytokine levels and promoted Tregs frequency in the AD population. Conclusion: These results imply that DF-MSCs are modulating inflammation through decreasing T cell apoptosis, inducing Treg expansion and stabilizing cytokine levels.


Lay abstract Background: Atopic dermatitis (AD) is an inflammatory cutaneous disorder characterized by immune-mediated inflammation and epidermal barrier dysfunction. There is no definite solution for the treatment of AD. We aimed to evaluate the immunomodulatory and immunosuppressive effect of dental stem cells (dental follicle-mesenchymal stem cell [DF-MSCs]) on AD. Materials & methods: We investigated the immunoregulatory potential of DF-MSCs on inflammatory response in AD and compared them with psoriasis and healthy individuals and the mechanism underlying it. Results: DF-MSCs significantly reduced apoptosis-related markers in immune cells, decreased inflammatory cytokine levels and promoted Treg frequency in the AD. Conclusion: Our findings provide basic evidence for the potential role of DF-MSCs as a cellular therapy option in the treatment of AD and shed light on future clinical studies.


Assuntos
Saco Dentário/imunologia , Dermatite Atópica/imunologia , Dermatite Atópica/terapia , Imunomodulação/imunologia , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/imunologia , Adolescente , Adulto , Feminino , Humanos , Imunidade , Masculino , Resultado do Tratamento , Adulto Jovem
11.
Anticancer Res ; 40(10): 5641-5647, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988888

RESUMO

BACKGROUND: Mesenchymal stem cells (MSCs) have gained remarkable attention because of their ability to dualistically regulate tumor growth. The main objective of this study was to evaluate the apoptotic effects of human bone marrow-derived (hBM) MSCs in combination with interferon gamma (IFN-γ) on MCF-7 breast cancer cells, and to determine the cytokines involved in the apoptotic process. MATERIALS AND METHODS: hBM-MSCs were co-cultured with MCF-7 cells either directly and indirectly for 72 h in-vitro. Levels of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), apoptosis and cytokines were analyzed. RESULTS: hBM-MSCs increased the apoptosis of MCF-7 cells partially through TRAIL in vitro. IFN-γ enhanced the apoptotic effect of hBM-MSCs (p<0.001). CONCLUSION: hBM-MSCs in combination with IFN-γ might be a suitable therapy for breast cancer.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Interferon gama/farmacologia , Células-Tronco Mesenquimais/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF/genética , Apoptose/efeitos dos fármacos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Técnicas de Cocultura , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Interferon gama/genética , Células MCF-7 , Células-Tronco Mesenquimais/citologia
12.
Immunotherapy ; 12(9): 665-674, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32489107

RESUMO

Asthma is a chronic inflammatory disease of the airways where exaggerated T helper 2 immune responses and inflammatory mediators play a role. Current asthma treatment options can effectively suppress symptoms and control the inflammatory process; however, cannot modulate the dysregulated immune response. Allergen-specific immunotherapy is one of the effective treatments capable of disease modification. Injecting allergens under the skin in allergen-specific immunotherapy can reduce asthma and improve the sensitivity of the lungs, however, has a risk of severe reactions. Mesenchymal stem cells have immunoregulatory activity with their soluble mediators and contact dependent manner. In this review, we focus on the current treatment strategies with mesenchymal stem cells in asthma as a new therapeutic tool and compare those with immunotherapy.


Assuntos
Asma/imunologia , Asma/terapia , Imunoterapia/métodos , Células-Tronco Mesenquimais/imunologia , Animais , Humanos , Camundongos
13.
Turk J Gastroenterol ; 31(5): 400-409, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32519960

RESUMO

BACKGROUND/AIMS: Crohn's Disease (CD) is a chronic inflammatory condition characterized by various abnormalities that lead to overly aggressive T-cell responses. Our in vitro experiments aimed to investigate the potential use of Dental Follicle Mesenchymal Stem Cells (DF-MSCs) to suppress the exaggerated immune response in inflamed and non-inflamed tissue of Crohn's Disease (CD). MATERIAL AND METHODS: Dental follicle tissues were obtained from extracted third molar teeth of 3 healthy volunteers who have no abscess or inflammatory diseases. Eleven patients included the experiment who had been diagnosed with CD and not received steroid maintenance therapy for more than 1 month. Mononuclear Cells (MNCs) were isolated from inflamed and non-inflamed tissue of CD. Isolated cells were stimulated with anti-CD3/anti-CD28 monoclonal antibodies in the presence and absence of DF-MSCs and analyzed for lymphocytes proliferation capacity and viability, T lymphocyte subsets, CD4+IL22BP and CD4+CD25+Foxp3+ regulatory T cell (Tregs) frequencies and cytokine levels. RESULTS: A significant downregulation of lymphocyte proliferation and CD4+IL22BP T cell ratio were found in inflamed cultures with DF-MSCs (p<0,005). Also, the frequency of Tregs increased with DF-MSCs (p<0,05). Pro-inflammatory cytokine levels (TNF-α and IL-6) were decreased (p<0,05) and IL-10 levels were increased (p<0,05) in the supernatant of inflamed cultures. CONCLUSION: DF-MSCs reduced the inflammatory immune response, induced Tregs and downregulated CD4+IL22BP T cell ratio in inflamed samples of CD patients, which may be exploited for significant therapeutic use.


Assuntos
Doença de Crohn/imunologia , Doença de Crohn/terapia , Saco Dentário/citologia , Imunidade Celular/imunologia , Transplante de Células-Tronco Mesenquimais , Adulto , Citocinas/metabolismo , Regulação para Baixo/imunologia , Feminino , Humanos , Ativação Linfocitária/imunologia , Masculino , Células-Tronco Mesenquimais/imunologia , Pessoa de Meia-Idade , Estudos Prospectivos , Subpopulações de Linfócitos T/imunologia , Resultado do Tratamento
14.
Mol Biol Rep ; 46(3): 2997-3008, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30850965

RESUMO

Natural killer (NK) cells have antifibrotic effects. We have evaluated the influence of rat bone marrow-mesenchymal stem cell (BM-MSC) treatment on liver histology, biochemical liver function tests, systemic immunoregulatory state and NK cell distribution in liver and peripheral blood in rat model of common bile duct (CBD) ligation and compared the results with the control group. Rats were divided into three groups: (1) CBD ligated (CBDL) rats received phosphate-buffered saline (CBDL + PBS group) or (2) MSC (CBDL + MSC group) and sham-operated rats received MSC (healthy + MSC group). We found significantly decreased fibrosis scores with BM-MSC treatment in CBDL rats compared to the control (CBDL + PBS) group while no fibrosis developed in sham operated (healthy + MSC) group. BM-MSC treatment has decreased the inflammation as reflected by the significantly decreased T cell proliferation and inflammatory cytokine concentrations from splenocyte culture and liver tissue itself compared to CBDL + PBS. NK cells both in parenchyme and portal areas decreased significantly in liver and blood in CBDL + PBS compared to healthy + MSC while they were found to be increased in CBDL + MSC compared to CBDL + PBS rats. In conclusion, BM-MSCs may suppress hepatic fibrosis accompanied by expanded intrahepatic NK cells in CBDL rats. Thus, our animal study shows that MSC treatment holds great promise for treatment of patients with end-stage liver diseases through a possible mechanism by adopting the NK cell population and new studies investigating the role of NK cells and clinical fibrosis are warranted.Trial registration number: Marmara University Animal Care and Use Committee approval code: 73.2013.mar.


Assuntos
Fibrose/genética , Cirrose Hepática/patologia , Células-Tronco Mesenquimais/metabolismo , Animais , Ducto Colédoco/cirurgia , Modelos Animais de Doenças , Fibrose/imunologia , Células Matadoras Naturais/metabolismo , Células Matadoras Naturais/fisiologia , Ligadura , Fígado/patologia , Cirrose Hepática/genética , Testes de Função Hepática , Masculino , Transplante de Células-Tronco Mesenquimais/métodos , Ratos , Ratos Sprague-Dawley
15.
Dent Traumatol ; 34(3): 188-200, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29528563

RESUMO

BACKGROUND/AIM: Ectoine is an amino acid that can preserve osmotic balance and has more preservative activity than other osmoregulators. There are no published reports on the osmoregulators' effects on viability or differentiation of dental stem cells. The aim of this study was to investigate the effect of Ectoine as a storage media on the viability and differentiation potential of human periodontal ligament mesenchymal stem cells (hPDLMSCs). MATERIALS AND METHODS: hPDLMSCs were obtained from impacted third molar teeth. The cells were isolated, submitted to trilineage differentiation, and characterized by flow cytometer (FC). hPDLMSCs were incubated with different media containing Ectoine, complete DMEM (cDMEM), Ectoine+cDMEM, milk, and tap water for 2, 6, 12, and 24 h. The cells were analyzed by FC for viability, early-apoptosis, late apoptosis, and necrosis rates. Osteogenic and fibroblastic differentiation in hPDLMSCs were investigated by Alizarin red stain and vimentin expression. RESULTS: All treated groups showed significant decreases in cell viability after 2 h. Significant increases were detected in the number of dead cells between 2 and 12 h in all groups except the Ectoine+cDMEM group. The deposition of mineral matrix nodules was significantly higher in cells cultured with Ectoine+cDMEM compared with the other media. Higher vimentin expressions were detected in cells cultured with cDMEM and Ectoine+cDMEM media, respectively. CONCLUSIONS: Ectoine added to cDMEM media, promoted cell survival plus osteogenic and fibroblastic differentiation of hPDLMSCs.


Assuntos
Diamino Aminoácidos/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Ligamento Periodontal/citologia , Adolescente , Adulto , Animais , Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Meios de Cultura/farmacologia , Citometria de Fluxo , Humanos , Leite , Água/farmacologia
16.
Turk J Med Sci ; 47(2): 675-680, 2017 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-28425265

RESUMO

BACKGROUND/AIM: Diabetes mellitus inhibits wound-induced angiogenesis, impairs the wound healing process, and leads to the development of chronic wounds. Ankaferd BloodStopper (ABS) is a new and promising local haemostatic agent. Although the mechanism of ABS-mediated haemostasis is well established, little is known about the associated histological and biochemical tissue reactions. The aim of this study was to evaluate the effects of this new-generation local haemostatic agent on short-term soft-tissue healing in streptozotocin (STZ)-treated rats. MATERIALS AND METHODS: The 24 Wistar albino rats used in this study were divided into STZ-treated (STZ, n = 12) and nontreated groups (control, n = 12). Four days prior to surgery, rats in the STZ group were subcutaneously administered 60 mg/kg STZ intraperitoneally, while rats in the control group were administered 1 mL saline/kg. An incision was made in the dorsal dermal tissue of all rats, and either ABS or no haemostatic agent (NHAA) was applied to the wound before suturing. All of the rats were euthanised on postoperative day 4. Blood and skin samples were evaluated biochemically and histologically. RESULTS: The results showed that STZ treatment impaired soft-tissue healing, assessed by measuring glutathione and lipid peroxidation levels. Moreover, while good histological results were obtained in the control group treated with ABS, there were fewer benefits in the STZ-treated group. CONCLUSION: ABS's benefits in the control group seemed to lose their effectiveness under STZ medication.


Assuntos
Diabetes Mellitus Experimental/metabolismo , Extratos Vegetais/farmacologia , Pele/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Animais , Colágeno/metabolismo , Glutationa/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar , Pele/lesões , Pele/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
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