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Ramóna Pap Emese Ugor Tímea Litvai Lilla Prenek József Najbauer Péter Németh Tímea Berki 《Immunobiology》2019,224(2):285-295
Objective
Functional disturbances in regulatory T cells (Treg) have been described in autoimmune diseases, and their potential therapeutic use is intensively studied. Our goal was to investigate the influence of glucocorticoid hormone on the in vitro differentiation of Treg cells from thymic and splenic CD4+ T cells under different conditions to establish methods for generating stable and functionally suppressive iTregs for future use in adoptive transfer experiments.Methods
Thymic and splenic CD4+ T lymphocytes were isolated from 3 to 4 week-old control and in vivo dexamethasone (DX) pretreated BALB/c mice using magnetic bead negative selection, followed by CD25 positive selection. The cells were cultured with anti-CD3/CD28 beads and IL-2 in the presence or absence of TGFβ and/or DX for 3–6 days. Multiparametric flow cytometry was performed using CD4, CD25, CD8, TGFβ (LAP) cell surface and Foxp3, IL-4, IL-10, IL-17 and IFNγ intracellular staining. Quantitative RT-PCR was performed to measure IL-10, TGFβ cytokine and Foxp3 mRNA levels.Results
Differentiation of thymus-derived CD4+ cells in vitro into iTreg cells was most effective (24–25%) when anti-CD3/CD28 beads, IL-2, and TGFβ were present. Splenic CD4+ T cell expansion under same conditions resulted in a higher (44–45%) iTreg cell ratio that further increased (up to 50% Treg) in the presence of DX. Elevated immunosuppressive cytokine (IL-10 and TGFβ) production by iTregs could be measured both at protein and mRNA levels without elevation of Th1/Th2 or Th17 cytokine production. We got the highest iTreg ratio (74%) and TGFβ production when CD4+CD25+ splenic T cells were stimulated in the presence of TGFβ. In vivo 4 days DX pretreatment resulted in enhanced in vitro expansion and Foxp3 expression of thymus-derived iTregs and decreased differentiation of spleen-derived iTreg cells. In these Tregs the relative expression of IL-10 mRNA significantly decreased under all in vitro stimulation conditions, while TGFβ mRNA level did not change.Conclusion
DX promotes the expansion of thymic and splenic Treg cells, and enhances Foxp3+ expression and the production of immunosuppressive cytokines IL-10 and TGFβ in vitro. In vivo pretreatment of mice with DX inhibited the immunosuppressive cytokine production of in vitro differentiated Treg cells. We hypothesize that patients receiving GC therapy may need special attention prior to in vitro expansion and transplantation of Treg cells. 相似文献3.
Ling Zhou Xuping Niu Jiannan Liang Junqin Li Jiao Li Yueai Cheng Yanfeng Meng Qiang Wang Xiaoli Yang Gang Wang Yu Shi Erle Dang Kaiming Zhang 《Acta histochemica》2018,120(8):734-740
Objective
To directionally-differentiate dermis-derived mesenchymal stem cells (DMSCs) into vascular endothelial cells (VECs) in vitro, providing an experimental basis for studies on the pathogenesis and treatment of vascular diseases.Methods
After separation by adherent culture, VEC line supernatant, vascular endothelial growth factor (VEGF), bone morphogenetic protein-4 and hypoxia were used for the differentiation of VECs from DMSCs. The cell type was authenticated by flow cytometry, matrigel angiogenesis assay in vitro, and immunofluorescent staining during differentiation. The VEGF concentration was investigated by enzyme-linked immunosorbent assay.Results
After 28 days of differentiation, the cell surface marker CD31 was significantly positive (80%–90%) by flow cytometry in the VEC line-conditioned culture, which was significantly higher than in the other groups. Differentiated DMSCs had the ability to ingest Dil-ac-LDL and vascularize in the conditioned culture, but not in the other groups. In the VEC line supernatant, the concentration of VEGF was very low. The VEGF concentration changed along with the differentiation into VECs in the medium of the conditioned culture group.Conclusion
VEC line supernatant can induce the differentiation of DMSCs into VECs, possibly through the pathway except VEGF. 相似文献4.
Introduction
High Power Laser therapy (HPLT) can damage tissues due to its high skin absorption and side effects. The objective of this study was to determine the protective effect of human adipose-derived stem cells (hADSCs) against HPLT-mediated fat tissue damage after fat grafts in an in vivo study.Methods
To determine the viability of fat grafts with transplanted hADSCs, high power laser (HPL) irradiation was performed using a 830?nm gallium–aluminum–arsenide (Ga–Al–As) laser. In the in vivo study, fat grafts with hADSCs/Dulbecco’s modified Eagle’s medium (DMEM) were transplanted and HPL irradiation of each nude mouse was performed per protocol for a period of 13 weeks. Vascular endothelial growth factor (VEGF) and cluster of differentiation 31 (CD31) levels of hADSCs were quantified by immunofluorescent staining using anti-VEGF antibody and anti-CD31 antibody, respectively, along with human mitochondrial (hMT) antibody.Results
Compared to the HPLT?+?DMEM group, HPLT?+?hADSCs group showed increase in the number of viable cells of hADSCs in fat grafts, fat graft survival rate (weights and volumes), and expression levels of VEGF and CD31 in treated nude mice. Results of the in vivo study using nude mice and immune cytokine array suggest that hADSCs have potential protective effect against HPLT-mediated fat tissue damage.Discussion
hADSCs could be applied in clinical fields by inhibiting HPLT-mediated side effects. 相似文献5.
Mohana Priya Anitha Thomas Ramani Kumar Visalakshi Jeyaseelan Inbam Indrasingh Suganthy Rabi 《Journal of the Anatomical Society of India》2017,66(1):15-19
Introduction
Langerhans cells (LCs), a type of dendritic cells are the professional antigen presenting cells present in the mucosa surfaces. They play an important role in antitumor immune response. The present study aims to find out the morphology and distribution of CD1a positive LCs in normal and squamous cell carcinoma of cervix.Methods
Twenty two normal and eleven ectocervical specimens with squamous cell carcinoma were processed for immunohistochemistry and stained with monoclonal mouse anti-human CD1a (Dako, USA). The morphology of CD1a positive LCs was studied using Olympus BX43 microscope. Morphometric analysis was done using Cellsens imaging analysing software.Results
There was a statistically significant difference in the number of LCs between normal (8 ± 2.76) and squamous cell carcinoma of cervix (5.36 ± 2.88). In the region of lymphatic infiltration both in epithelium and lamina propria, there were more number of LCs and most of the cells lost their dendritic processes in squamous cell carcinoma. 31.77% of the cells had no dendritic processes. The difference in the mean diameters of LCs was statistically significant (p = 0.005) between normal and squamous cell carcinoma of cervix.Discussion
Fewer number of CD1a positive LCs and their loss of dendritic processes in the squamous cell carcinoma of cervix compared to normal cervix indicate that immune responses are suppressed in patients with cancer. 相似文献6.
Jianli Liu Sha Han Ronghang Hu Jian Huang Renya Zhang Kaizhi Li Lu Li Guoan Zhang Hongli Zhao 《Pathology, research and practice》2018,214(9):1352-1355
Background
Esophageal squamous cell carcinoma (ESCC) is a common cancer in East Asia and some other parts of the world with a dismal prognosis. CD51 (integrin αv),a transmembrane glycoprotein responsible for cell-to-matrix binding has been found to enhance tumor progression. However, its expression and clinicopathological significance in ESCC tumors are not fully understood. The purpose of this study was to investigate the expression level of CD51 and to explore its clinicopathological significance in ESCC.Methods
The expression of CD51 in 122 ESCC samples was examined by immunohistochemistry and its clinicopathological significance was evaluated.Results
The expression of CD51 was observed in tumor cell membrane and/or cytoplasm, with a positive rate of 48.36% (59/122). High expression of CD51 was significantly associated with lymph node metastasis (P?=? 0.031), tumor size (P?=? 0.028) and invasive depth (P?=? 0.027). Kaplan-Meier analysis revealed that positive expression of CD51 was correlated with poor overall survival of ESCC patients (P?=? 0.015). Multivariate analysis suggested that CD51 was an independent prognositic factor for ESCC (hazard ration = 1.604; 95% CI, 1.086–2.368; P?=? 0.017).Conclusion
These data suggested CD51 was a predictor for the prognosis of ESCC patients. 相似文献7.
V. Deneys C. Thiry A. Frelik C. Debry B. Martin C. Doyen 《Transfusion Clinique et Biologique》2018,25(1):2-7
Objectives
Recently, daratumumab has been included in the therapeutic strategies for myeloma patients. This molecule is an antibody directed against CD38, strongly expressed on plasma cells. Nevertheless, as CD38 is also present on erythrocyte membrane, daratumumab interferes with immunohaematological tests, complicating the selection of compatible blood.Methods
A total of 14 patients treated by daratumumab have been followed in our transfusion laboratory. Among them, 11 have been transfused. Dithiotreitol (DTT) has been used to inhibit the daratumumab's interference, in the pre-transfusion tests (irregular antibody screening and cross-match).Results
The red blood cell treatment with DTT has been very efficacious to inhibit the daratumumab's interference in 13 patients out of 14. Some precautionary measures had to be taken into account, especially the pH and the storage conditions. An extended pheno/genotype was an additional security element in the selection of compatible blood. To simplify and to optimize the laboratory practices, a decisional flow chart has been written.Conclusion
DTT red blood cell treatment is very useful and efficacious in the pre-transfusion tests of patients treated with daratumumab. It allows to avoid the selection of blood bags only on the basis of an extended pheno/genotype, what is more secure and more ethical with respect to other at higher risk patients. A clear decisional flow chart allows a quality assurance gait. Collaboration with physicians is essential. 相似文献8.
Yu Pu Hongyi Liu He Xu Huanhai Liu Yin Cheng Xiaoping Chen Weihua Xu Yaping Xu Jingping Fan 《Pathology, research and practice》2018,214(8):1210-1217
Background
To investigate the effects of IL-1β on the migration of olfactory epithelium neural stem cells (OENSCs), and to assess the mechanisms.Methods
The effects of different concentrations of IL-1β on cell proliferation, apoptosis and migration were evaluated by cell counting assay, flow cytometry and transwell migration assay, respectively. Matrix metalloproteinase (MMP)-2 and MMP-9 expression in both protein and mRNA levels were detected. Small interfering RNA (siRNA) technique was employed to knockdown MMP-2 and MMP-9 expression. Additionally, c-Jun N-terminal kinase (JNK) and nuclear factor-κB (NF-κB) inhibitors were applied to assess the potential signaling pathways involved in the effects of IL-1β on cell migration.Results
IL-1β promoted cell migration of OENSCs in a concentration-dependent manner at the concentration range of 0–80?ng/ml, but did not affect cell proliferation and apoptosis. Mechanically, IL-1β promoted MMP-2 and MMP-9 expressions. Knockdown of MMP-2 or MMP-9 could significantly reduce IL-1β-induced cell migration. IL-1β activated JNK, NF-κB, Extracellular Signal-Regulated Kinase (ERK) and p-65 phosphorylation. Finally, we evidenced that inhibition of JNK or NF-κB significantly inhibited cell migration.Conclusion
Our study demonstrated that IL-1β promoted the migration of OENSCs through activating MMP expression. Moreover, JNK and NF-κB signaling pathways were involved in the regulation. This study provides important experimental evidence for the application of OENSCs in the transplantation therapy. 相似文献9.
Aims
Cyclin D1, generally considered to be absent in chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL), has been reported in the proliferation centres (PCs) of recent CLL/SLL cases. Cyclin D1 immunostaining in CLL/SLL may lead to diagnostic confusion. The objective of this study was to identify the types of stained cells and the impact on diagnosis.Methods
Cyclin D1 expression was assessed by immunostaining samples from 46 cases of CLL/SLL. CD68 and double immunostaining with CD20/CyclinD1, CD68/CyclinD1, and CD163/CyclinD1 were then performed in cases of CLL/SLL positive for cyclinD1 in the PCs.Results
Dim-positive cyclin D1 staining in randomly scattered cells in the CLL/SLLs were observed in 38/46 cases (82.6%). In five (10.9%) cases, more than 50 cyclin D1-positive cells per high-power field were detected within the PCs in CLL/SLL with weak to moderate intensity. Double immunochemical staining in these cases showed that cyclin D1 in these positive cells was mostly co-expressed with CD68 and CD163 and the cells were negative for CD20.Conclusions
The cyclin D1-positive CLL/SLL cells in this study were mostly histiocytes. The expression of cyclin D1 by histiocytes may mimic cyclin D1+ CLL/SLL; thus, the recognition of cyclin D1 expression by non-lymphoid cells in lymphoma is important. 相似文献10.
Ting Liu Hong Zhang Xuesong Yang Xiaojie Li Yi Shi Weidong Niu Tingjiao Liu 《Pathology, research and practice》2018,214(2):296-302
Objective
The aim of this study is to investigate the expressions of p16 and HPV16/18(E6) in oral lichen planus (OLP) and malignant transformed OLP (MT-OLP).Study design
The expression of p16 and HPV16/18(E6) in 40 cases of OLP and 6 MT-OLP was assessed by immunohistochemical staining. Twenty four cases of normal oral mucosa were used as controls.Results
Compared to normal oral mucosa, the expression of p16 and HPV16/18(E6) protein increased in OLP and MT-OLP. And there was a correlation between p16 expression and HPV infection in OLP and OLP malignant lesions (p?<?0.0001).Conclusions
The expression of p16 protein might predict HPV16/18 infection in OLP. And HPV16/18(E6) infection might contribute to OLP malignant transformation. 相似文献11.
Background
The mucosal layer plays an important role in regulating the intestinal barrier function. However, the underlying mechanisms of intestinal barrier dysfunction caused by trauma-hemorrhagic shock (THS) are still unknown.Methods
In this study, we examined the barrier damages, inflammatory responses as well as the metabolic changes of the mucosal layer of the colon in a THS rat model.Results
The results showed that compared to the rats treated with trauma only, THS induced marked failure of intestinal barrier characterized by increased intestinal permeability, inflammatory cell infiltration and decreased expression of genes involved in epithelial integrity. Moreover, decreased colonic mucus content and goblet cell numbers indicated that the mucosal layer was also impaired in response to THS. This was companied by the anomalous inflammatory responses in the tissue. Finally, microdialysis catheter examination showed that metabolites including glycerol, glucose, lactate and pyruvate, glutamate and glutamine were also altered by THS.Conclusion
Our results provide evidence that mucus layer-associated metabolic changes may contribute to the THS-induced intestinal barrier dysfunction. 相似文献12.
Prasanna Lokadolalu Chandracharya Rohini Alva Anjaneyalu Konuri Ashok Kumar 《Journal of the Anatomical Society of India》2018,67(1):80-85
Introduction
The present study was undertaken to know the effect of folic acid (FA) supplementation and FA absence diet during pregnancy on the number of implantation as well as their endometrial changes.Methods
Eighteen Wistar strain Albino rats were randomly divided into three groups and given different diets: Control group with normal diet, group with FA supplementation diet, and group with FA absent diet (with added Succinyl Sulfathiazole) for 5 weeks. The number of coloured thickenings along the uterine horns were identified by injecting 1% Evan’s blue due solution. The sites of embryo implantation were fixed in 10% buffered formalin for 8 hours and embedded.Result
Average number of implantation observed in pregnant dams fed with FA supplementation diet was 10 in contrast it was 7 in diet with FA absent diet and 8 in control groups. Histologically, implantation site in FA supplemented group showed favorable endometrial environment than the other groups.Discussion
FA is essential in successful implantation by providing favorable receptive environment to receive the implantation-competent blastocyst for a successful pregnancy. 相似文献13.
Background
Malassezia furfur is lipodependent yeast like fungus that causes superficial mycoses such as pityriasis versicolor and dandruff. Nevertheless, there are no standard reference methods to perform susceptibility test of Malassezia species yet.Aims
Therefore, in this study, we evaluated the optimized culture medium for growth of this lipophilic yeast using modified leeming-Notman agar and colorimetric resazurin microtiter assay to assess antimycotic activity of fluconazole against M. furfur.Results
The result showed that these assays were more adjustable for M. furfur with reliable and reproducible MIC end-point, by confirming antimycotic activity of fluconazole with MIC of 2 μg/ml.Conclusion
We conclude that this method is considered as the rapid and effective susceptibility testing of M. furfur with fluconazole antifungal activity. 相似文献14.
Silas Antonio Juvencio de Freitas Filho João Paulo Silva Servato Rodrigo Tavares de Sá Carla Silva Siqueira Paulo Rogério de Faria Adriano Mota Loyola Sérgio Vitorino Cardoso 《Pathology, research and practice》2018,214(6):876-880
Objective
Histones regulate chromatin density and therefore influence gene expression and cellular proliferation. These properties are modified by methylation, acetylation and phosphorylation of histones. The aim of this study was to investigate the variation of specific modified histones in actinic cheilitis (AC) and squamous cell carcinoma of the lip (SCCL).Methods
Samples of non-neoplastic tissue of the lip (NNTL, n?=?9), AC (n?=?33), and SCCL (n?=?27) were submitted to immunohistochemistry to detect the modified histones H3K36me3, H3K9ac, H4K12ac, and H3S10?ph.Results
Reactivity for all of the modified histones was significantly decreased from NNTL to AC, but not from AC to SCCL. Dysplasia in AC or histological grade in SCCL were not related to the reactivity of any modified histones.Conclusions
Histone modifications are related to initial actinic damage, but not to malignant transformation in the lip. 相似文献15.
Wen-Jing Liu Li Zhou Zhi-Yong Liang Wei-Xun Zhou Lei You Tai-Ping Zhang Yu-Pei Zhao 《Pathology, research and practice》2018,214(2):228-232
Background
It was found that G-protein-coupled receptor kinase 3 (GRK3) played key biological roles in some cancers. However, its associations with clinicopathologic features and prognosis in pancreatic ductal adenocarcinoma (PDAC) remain unknown.Methods and methods
Expression of GRK3 was detected, using tissue microarray-based immunohistochemistry, in paired formalin-fixed paraffin-embedded tumor and non-tumor samples from 165 patients with PDAC after curative resection, and was further correlated with clinicopathologic parameters and cancer-specific survival (CSS).Results
It was shown that GRK3 expression was much lower in tumor than in non-tumor tissues. Moreover, expression of GRK3 in tumor tissues was significantly associated with gender and T stage. Univariately, high GRK3 expression was predictive for favorable CSS, along with some conventional clinicopathologic variables. In multivariate Cox regression test, GRK3 expression remained to be a significant prognostic marker for PDAC. Finally, combination of GRK3 with some clinicopathologic variables, especially N stage, obtained more precise prediction for CSS.Conclusions
Our data suggested that expression of GRK3 was down-regulated in PDAC and was an independent prognostic factor. 相似文献16.
Christopher Kofahl 《Patient education and counseling》2018,101(12):2170-2178
Objective
About 800 of the 13,000 members of the German Tinnitus Association (DTL) are active in self-help groups (SHGs). This study analyzes whether SHG-participation is associated with tinnitus-related Health Literacy (HLit) and Quality of Life (QoL).Methods
In a cross-sectional study 1108 tinnitus patients in- and outside of SHGs administered a questionnaire containing tinnitus-related burden, QoL, tinnitus knowledge, self-management, assessment of SHGs, and socio-demographics. Participants were divided into four subgroups: (1) active SHG-members (19.6%), (2) former SHG-members (10.6%), (3) DTL-members, but not in SHG (57.9%), (4) neither DTL- nor SHG-members (11.9%).Results
Participant were 59.7% male and 61.3 years on average. SHG-attendees are on average 5 years older than non-attendees, and have a lower education, while there are no differences in gender-distribution. Regression analyses show significant associations between SHG-participation and tinnitus knowledge, coping and self-esteem. QoL, however, is not associated with SHG-participation. SHG-members report considerable further benefits from SHG-membership.Conclusions
Despite the limitations through the cross-sectional design, it seems more likely that tinnitus-related HLit and other benefits are a result of SHG-participation than vice versa.Practice implications
Health care providers should inform their patients about SHGs and encourage them to consider a SHG as a possible option for their self-management. 相似文献17.
Nancy de los Ángeles Segura-Azuara Irma E. Eraña-Rojas Mildred V. López-Cabrera 《Educación Médica》2018,19(6):355-358
Introduction
Simulations make it possible to acquire various skills in a risk-free environment. The objective of this study was to assess medical student? performance in a simulation-enriched learning scenario in renal disease.Methods
2 renal scenarios were designed for implementation in high-fidelity simulations, using a rubric to assess small student teams’ performance. Good Judgment Debriefing was used as feedback to the students, once the simulation had ended. Finally, students then completed a self-evaluation of their performance.Results
54 students voluntarily participated in this study. Student teams performed the best in communication, collaboration and understanding of pathophysiology skills.Conclusions
Communication skills are of great importance in the medical field, both with healthcare team as with the patient. Students must strengthen their performance in therapy implementation and differential diagnoses before entering clinical rotations. This activity allows deep reflection and analysis of specific area performance, which can augment confidence on those where performance is high; and identify weakness areas that will lead to designing new activities to strengthen them. 相似文献18.
Li Yang Xuefeng Tang Xue Peng Dan Qian Qiaonan Guo Hong Guo 《Pathology, research and practice》2018,214(8):1081-1086
Background
Primary intestinal NK/T cell lymphoma is rare but aggressive and exhibits a poor prognosis. Little is known about its clinical characteristics because few studies with small sample sizes have been reported.Aims
To provide clinicopathological features and endoscopic findings and to summarize the treatment outcomes of primary intestinal NK/T cell lymphoma to improve our understanding of this disease.Methods
Between January 2011 to December 2016, 13 patients with confirmed primary gastrointestinal NK/T cell lymphoma at our center were described, and an updated literature review was provided.Results
In this series of 13 cases, 69.23% were men, the median age was 39 years, and the median survival was 6 months. The common clinical manifestations included abdominal pain (76.92%) and gastrointestinal bleeding (46.15%). Lymphomas were common in the large intestine (69.23%). In 76.92% of patients, the clinical staging was stage I, and all 13 patients manifested ulcerative lesions and no tumor mass on endoscopy. The clinical characteristics of primary intestinal NK/T cell lymphomas were similar to results in existing literature.Conclusion
Intestinal NK/T cell lymphoma shows nonspecific clinical features and poor prognosis, which is mainly expressed as ulcers on endoscopy. Emergency surgery may be an adverse prognostic factor of lymphoma, since it is prone to progress toward gastrointestinal perforation. 相似文献19.
Shu-Xu Du Yong-Rui Jia Si-Qi Ren Xiao-Jun Gong Hong Tang 《Advances in medical sciences》2018,63(1):134-139