Progress in the regulatory effects of tumor-derived exosomes on macrophage polarization / 中华微生物学和免疫学杂志

Mononuclear macrophages are versatile cells that can have different responses to various microenvironmental signals. Under different stimuli of circumstances, macrophages can be fully polarized into classically activated macrophages (M1) and alternatively activated macrophages (M2), which are the extremes of a continuum of functional states. Nuclear factor-κB, cyclooxygenase 2, anoxia status, proto-oncogene MYC, Toll-like receptor signaling pathway, Notch signaling pathway and cytokines are all closely involved in the transition of tumor-associated macrophages from M1 to M2 phenotype. Macrophages that infiltrate tumor tissues are driven by tumor-derived cytokines to acquire a polarized M2 phenotype. These functionally polarized cells play a key role in the subversion of adaptive immunity and in inflammatory circuits that promote tumor development and progression. Exosomes derived from tumors have the characteristics of tumor cells and could participate in multiple processes of tumorigenesis and development. This review focused on exosomes derived from various cancer cells and discussed the role of the payloads of tumor-derived exosomes in modulating macrophage polarization in the tumor immune microenvironment and the intracellular signal mechanisms involved.

The clinical analysis of 12 patients with immunoglobulin G4 related sialoadenitis and literature review / 中华风湿病学杂志

Objective@#To explore the clinical characteristics of Immunoglobulin G4 (IgG4) related sialoadenitis, to analyze the difference between the IgG4 related sialoadenitis and Sjögren′ syndrome (SS) and to summarize the treatment method and prognosis of the disease, so as to help clinical diagnosis and appro-priate treatment.@*Methods@#According to inclusion criteria and exclusione criteria, we collected 12 cases of IgG4 related sialoadenitis patients and 78 cases of SS patients from the First Affiliated Hospital of Xinjiang Medical University from 2015-2017. The clinical manifestations, laboratory test, pathological examinations, imaging examinations and the effects of treatment of IgG4 related sialoadenitis were retrospectively anal-yzed. Several aspects of the examination were compared with SS. The count data was analyzed by chi-square test or Fisher exact probality using Statistical program for social sciences (SPSS) 19.0 software.@*Results@#Character-istics of IgG4 related sialoadenitis was that one or more pairs of salivary glands and lacimal glands were enlar-ged with increasing serum IgG4 levels and IgG4+ plasma cell infiltration. Compared with SS, sialoadenitis enl-argement (12/12 vs 18/78, χ2=24.339, P<0.01), dry eyes and mouth (9/12 vs 78/78, P<0.01), serum IgG4 (12/12 vs 0/78, χ2=81.554, P<0.01), antinuclear antibodies (1/11 vs 78/78, χ2=71.030, P<0.01), anti-SSA antibody (0/9 vs 68/78,χ2=31.001, P<0.01), anti-SSB antibody (0/9 vs 36/78, χ2=5.311, P=0.021), anti-Ro-52 antibody (0/9 vs 70/78, χ2=35.824, P<0.01), infiltration of IgG4 positive plasma cell (12/12 vs 0/78, χ2=81.554, P<0.01), therapeutic efficacy of glucocorticoid (6/6 vs 0/34, P<0.01) was statistically significant.@*Conclusion@#IgG4 related sialoadenitis has remarkable characteristics in clinical manifestations, serology, pathology and imaging examinations. Although IgG4 related sialoadenitis and SS have many similarities, we still need to diagnose the disease as early as possible and set up a reasonable treatment plan for patients.

The clinical analysis of 12 patients with immunoglobulin G4 related sialoadenitis and literature review / 中华风湿病学杂志

Objective To explore the clinical characteristics of Immunoglobulin G4 (IgG4) related sialoadenitis,to analyze the difference between the IgG4 related sialoadenitis and Sj(o)gren'syndrome (SS) and to summarize the treatment method and prognosis of the disease,so as to help clinical diagnosis and appropriate treatment.Methods According to inclusion criteria and exclusione criteria,we collected 12 cases of IgG4 related sialoadenitis patients and 78 cases of SS patients from the First Affiliated Hospital of Xinjiang Medical University from 2015-2017.The clinical manifestations,laboratory test,pathological examinations,imaging examinations and the effects of treatment of IgG4 related sialoadenitis were retrospectively anal-yzed.Several aspects of the examination were compared with SS.The count data was analyzed by chi-square test or Fisher exact probality using Statistical program for social sciences (SPSS) 19.0 software.Results Characteristics of IgG4 related sialoadenitis was that one or more pairs of salivary glands and lacimal glands were enlarged with increasing serum IgG4 levels and IgG4+ plasma cell infiltration.Compared with SS,sialoadenitis enlargement (12/12 vs 18/78,x2=24.339,P＜0.01),dry eyes and mouth (9/12 vs 78/78,P＜0.01),serum IgG4 (12/12 vs 0/78,x2=81.554,P＜0.01),antinuclear antibodies (1/11 vs 78/78,x2=71.030,P＜0.01),anti-SSA antibody (0/9 vs 68/78,x2=31.001,P＜0.01),anti-SSB antibody (0/9 vs 36/78,x2=5.311,P=0.021),anti-Ro-52 antibody (0/9 vs 70/78,x2=-35.824,P＜0.01),infiltration of IgG4 positive plasma cell (12/12 vs 0/78,x2=81.554,P＜0.01),therapeutic efficacy of glucocorticoid (6/6 vs 0/34,P＜0.01) was statistically significant.Conclusion IgG4 related sialoadenitis has remarkable characteristics in clinical manifestations,serology,pathology and imaging examinations.Although IgG4 related sialoadenitis and SS have many similarities,we still need to diagnose the disease as early as possible and set up a reasonable treatment plan for patients.

Expressions of interleukin-21 and interleukin-22 in Kimura's disease / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To investigate the expressions of interleukin (IL)-21 (IL-21) and IL-22 in patients with Kimura's disease (KD).</p><p><b>METHODS</b>Expressions of IL-21 and IL-22 were examined immunohistochemically in 36 patients with KD and 7 normal controls. The integral absorbance (IA) of the two groups was compared. Meanwhile, clinical data were reviewed.</p><p><b>RESULTS</b>The IA of IL-21 [M(Q): 1 373 418 (1 800 926)] and IL-22 [M(Q): 462 086(484 672)] in KD was significantly higher than those in normal controls [M(Q): 70 445(44 658), 51 599(71 241), P < 0.05]. The overexpression of IL-21 was significantly associated with pruritus (Z = -1.993, P < 0.05). Moreover, IL-21 was identified for disease recurrence (Z = -2.303, P < 0.05). There was a significant association between the expression of IL-22 and the number of affected sites (Z = -1.979, P < 0.05). In addition, IL-22 was significantly higher in the high-eosinophils group than in the low-eosinophils group (Z = -2.025, P < 0.05). There was no association between IL-21, IL-22 and age, gender, laterality, maximum size.</p><p><b>CONCLUSIONS</b>IL-21 and IL-22 may be involved in the pathogenesis of KD.</p>

Expression of serum and urinary vascular endothelial growth factor-A and epidermal growth factor-like domain 7 in proliferating hemangioma treated with propranolol / 华西口腔医学杂志

<p><b>OBJECTIVE</b>This study aims to investigate the expression levels of serum and urinary vascular endothelial growth factor-A (VEGF-A) and epidermal growth factor-like domain 7 (EGFL7) in proliferating infantile hemangioma patients under propranolol treatment.</p><p><b>METHODS</b>Propranolol (0.5-2 mg x kg(-1)) was orally administered to 30 infants every day for 4-8 months. The Achauer method was used to measure the tumor radius and thus evaluate the clinical curative effects of the treatment. Enzyme-linked immunosorbent assay was used to measure the serum and urinary concentrations of VEGF-A and EGFL7 at 0, 4, and 12 weeks after the treatment.</p><p><b>RESULTS</b>The treatment response was excellent in 2 patients, good in 11, moderate in 14, and poor in 3. Serum VEGF-A (335.692 pg x mL(-1) ± 136.146 pg x mL(-1)) was high before the treatment and then significantly decreased after 4 weeks (264.853 pg x mL(-1) ± 122.120 pg x mL(-1)) and 12 weeks (211.345 pg x mL(-1) ± 104.035 pg x mL(-1)) of treatment (P < 0.05). Urinary VEGF-A (76.234 pg x mL(-1) ± 24.169 pg x mL(-1)) was high before the treatment and then significantly decreased after four weeks (56.454 pg x mL(-1) ± l6.111 pg x mL(-1)) and twelve weeks (34.728 pg x mL(-1)) ± 12.656 pg x mL(-1)) of treatment (P < 0.05). Serum and urinary EGFL7 also decreased after the treatment, showing a positive relationship with VEGF-A.</p><p><b>CONCLUSION</b>Propranolol can be safely and effectively used to treat proliferating infantile hemangiomas. This treatment can reduce the peripheral serum and urinary concentrations of VEGF-A and EGFL7 in affected children.</p>

Chondrogenic differentiation of rat synovial-derived mesenchymal stem cells / 中国组织工程研究

BACKGROUND:Compared with other sources of mesenchymal stem cells, synovial-derived mesenchymal stem cells have significant characteristics of chondrogenesis and cloning. Therefore, synovial-derived mesenchymal stem cells are one of the most promising seed cells in cartilage tissue engineering. OBJECTIVE:To isolate and culture synovial-derived mesenchymal stem cells of Sprague-Dawley rats, identify the multipotential differentiation and the potential ability of chondrogenic differentiation in three-dimensional culture condition. METHODS:The synovium tissue was harvested from Sprague-Dawley rats. The synovial-derived mesenchymal stem cells were isolated with typeⅠcol agen enzyme digestion method and cultured in vitro. The passage 3 cells were detected with giemsa staining, the cellcycle, adipogenic and osteogenic differentiation were determined. The passage 3 cells were centrifuged as pel ets and cultured in the chondriogenic medium for 21 days. And the pel ets were examined by toluidine blue staining, typeⅡcol agen immunohistochemical staining and RT-PCR. RESULTS AND CONCLUSION:The mesenchymal stem cells isolated from the synovium tissue of rats have the characteristics of mesenchymal stem cells, and exhibit fibroblast-like morphology after cultured in vitro. The multilineage differentiation potentials were also revealed. After the cellwere cultured in chondrogenic medium for 21 days, chondroid tissue was found, type II col agen and aggrecan could be detected positively by toluidine blue staining, typeⅡcol agen immunohistochemical staining, and expressed by RT-PCR examination. Therefore, synovial mesenchymal stem cells have a chondrogenic differentiation potential.

Chondrocyte supernatant induces chondrogenesis and pellet cultivation of rat synovial mesenchymal stem cells / 中国组织工程研究

BACKGROUND:Synovial mesenchymal stem cells have the ability of multilineage differentiation in vitro, which are expected to be seed cells for the treatment of cartilage defects in cartilage tissue engineering. Appropriate growth factors are critical for the chondrocyte differentiation of synovial mesenchymal stem cells. OBJECTIVE:To study the role of secreted factors by chondrocytes to induce chondrogenesis of synovial mesenchymal stem cells. METHODS:The synovial mesenchymal stem cells and chondrocytes were harvested from rat knee joints and cultured through the digestion method. The supernatant was col ected from chondrocytes, and centrifuged, filtered and cryopreserved. The third passage synovial mesenchymal stem cells centrifuged as pel ets were cultured in the chondrocyte supernatant for 21 days. And the cells morphology was examined and the type II col agen and aggrecan were detected through immunohistochemistry and RT-PCR. RESULTS AND CONCLUSION:The synovial mesenchymal stem cellpel ets cultured in the chondrocyte supernatant became cartilage-like tissue after 21 days. The type II col agen was detected positively in the matrix of synovial mesenchymal stem cellpel et immunohistochemical y. RT-PCR examination showed that the type II col agen and aggrecan expressed in the synovial mesenchymal stem cellpel et cultured in the chondrocyte supernatant. It suggested that synovial mesenchymal stem cellcould be induced to differentiate into chondrocytes depending on soluble factors secreted by chondrocytes.

Propranolol for proliferating hemangioma: therapeutic efficacy and expressions of vascular endothelial growth factor-A and hypoxia-inducible factor 1α in patients before and after treatment / 中华皮肤科杂志

Objective To evaluate the clinical efficacy of propranolol in treating proliferating infantile haemangiomas,and to measure the expression levels of vascular endothelial growth factor-A (VEGF-A) and hypoxiainducible factor 1α (HIF-1α) in sera and urine of patients during the treatment.Methods Thirty infants with proliferating haemangiomas were treated with propranolol at doses of 0.5-2 mg/kg per day.The radius of haemangiomas was measured,and blood and urine samples were obtained from these patients before,and at 4 and 12 weeks after the beginning of treatment.Clinical efficacy was estimated according to a four-graded scale as well as the feedback from parents of these patients.Enzyme-linked immunosorbent assay (ELISA) was performed to determine the serum and urine concentrations of VEGF-A and HIF-1α.Thirty check-up infants collected from the Department of Child Health Care served as the healthy controls.Statistical analysis was done by two-way analysis of variance followed by the least significant difference (LSD) test.Results After 12 weeks of treatment,clinical response was excellent in 2 patients,good in 11,moderate in 14,and poor in 3.The serum levels of VEGF-A and HIF-1α were (268.174 ± 95.056) μg/L and (10.809 ± 1.686) mg/L respectively in the control group,sequentially decreased in the patients from baseline to 4 and 12 weeks after the beginning of treatment (VEGF-A:(385.692 ± 136.146) vs.(264.853 ± 122.12) vs.(211.345 ± 104.035) μg/L; HIF-1α:(31.462 ± 7.458) vs.(21.454 ± 5.489) vs.(12.052 ± 3.623) mg/L).The trend in expression changes of VEGF-A and HIF-1α in urine samples was similar to that in blood samples in these patients.Positive correlation was observed between the expression level of VEGF-A and HIF-1α in sera (r=0.730,P＜ 0.05) and urine (r=0.667,P＜ 0.05) of these patients.Moreover,the levels of serum VEGF-A,urine VEGF-A,serum HIF-1α and urine HIF-1α were all negatively correlated with the time course following propranolol administration (r =-0.390,-0.689,-0.806,-0.683,P ＜ 0.05,0.01,0.05,0.01 respectively).Conclusion Propranolol is effective for the treatment of proliferating infantile haemangiomas,likely by reducing serum and urinary concentrations of VEGF-A and HIF-lα in children.

Chondrogenesis of synovial mesenchymal stem cells co-cultured with chondrocytes on the three-dimensional scaffold / 中国组织工程研究

BACKGROUND:Articular chondrocytes with the ability of autocrine and paracrine can provide the growth factors and microenvironment for synovial mesenchymal stem cels differentiating into the chondrocyte. The three-dimensional scaffold could provide space for cels adhesion, proliferation and differentiation. OBJECTIVE: To study the ability of chondrogenesis by co-culturing synovial mesenchymal stem cels and chondrocytes under the three-dimensional condition. METHODS:The synovial membrane and articular cartilage were harvested from rat knee joint. The synovial mesenchymal stem cels and chondrocytes were obtained through the method of enzyme digestion. The passage 3 synovial mesenchymal stem cels and passage 2 chondrocytes were co-cultured in the chitosan/I colagen composite scaffolds at the ratio of 1:2. Then, the cels/scaffold composite was harvested to be examined morphologicaly, histologicaly and immunohistochemicaly after being cultured 21 days. The confocal laser was also employed to detect the cels distribution in the scaffold. RESULTS AND CONCLUSION: After being cultured 72 hours, it could be observed from the cels/scaffold composite examined through the scanning electron microscope that the cels adhered on the surface of the scaffold and extracelular matrix surrounding the cels was seen on the scaffold. After being cultured 21 days, it could be found through the confocal laser scanning that the cels were wel-distributed on the scaffold, and cels decreased gradualy. Type II colagen was positive in the extracelular matrix immunohistochamicaly. It suggested from this study that the synovial mesenchymal stem cels could be co-cultured with chondrocytes in the chitosan/I colagen composite scaffolds and have the ability of chondrogenesis differentiation.

Preliminary study of chitosan/pcDNA-EGFP-TGFbeta1 nanoparticles used in the transfection of synovial-derived mesenchymal stem cells / 生物医学工程学杂志

The objective of this study is to explore the application possibility of chitosan/pcDNA-EGFP-TGFPbeta1 nanoparticles in the transfection of synovial-derived mesenchymal stem cells (SDMSCs). Chitosan/pcDNA-EGFP-TGFbeta1 nanoparticles were fabricated through method of ionic crosslinking. The SDMSCs were harvested from rabbit joints and cultured to passage 3. The SDMSCs were then transfected with chitosan/pcDNA-EGFP-TGFbeta1 nanoparticles. Scanning electronic microscope (SEM) was employed to detect the shape and diameter of the nanoparticles. The transfected SDMSCs were examined under the fluorescence microscope and detected through the flow cytometry (FCM). The SEM examination showed that the contour of the fabricated chitosan/pcDNA-EGFP-TGFbeta1 nanoparticles was round and its average diameter was 50 nm. After being cultured for 48 h, the SDMSCs transfected by chitosan/pcDNA-EGFP-TGFbeta1 nanoparticles could be detected under the fluorescence microscope, and the live SDMSCs could also be examined through FCM. The transfection rate was 8% - 10%. Therefore, it suggested that the chitosan/pcDNA-EGFP-TGFbeta1 nanoparticles fabricated through the method of ionic crosslinking could transfect the SDMSCs, but the transfection rate should be improved.