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1.
BMC Endocr Disord ; 24(1): 65, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38730329

ABSTRACT

OBJECTIVE: Diabetic patients are often comorbid with dyslipidemia, however, the relationship between high-density lipoprotein cholesterol(HDL-C) and diabetic retinopathy (DR) in the adult diabetic population remains to be fully elucidated.The aim of this study is to evaluate the associations between HDL-C and DR in the United States adults with diabetes. METHODS: A total of 1708 participants from the National Health and Nutrition Examination Survey (NHANES) 2005-2008 were enrolled in the present study. Fundus images of all study subjects were captured and evaluated using a digital camera and an ophthalmic digital imaging system, and the diagnosis of DR was made by the severity scale of the Early Treatment Diabetic Retinopathy Study (ETDRS).Roche Diagnostics were used to measure serum HDL-C concentration. The relationship of DR with HDL-C was investigated using multivariable logistic regression. The potential non-line correlation was explored with smooth curve fitting approach. RESULTS: The fully-adjusted model showed that HDL-C positively correlated with DR(OR:1.69, 95%CI: 1.25-2.31).However, an inverted U-shaped association between them was observed by applying the smooth curve fitted method. The inflection point of HDL-C(1.99mmol/l) was calculated by utilizing the two-piecewise logistic regression model. In the subgroup analysis, the inverted U-shaped nonlinear correlation between HDL-C and DR was also found in female, Non-Hispanic White, and lower age groups. CONCLUSION: Our study revealed an inverted U-shaped positive relationship between HDL-C and DR.The findings may provide us with a more comprehensive understanding of the association between HDL-C and DR.


Subject(s)
Cholesterol, HDL , Diabetic Retinopathy , Humans , Diabetic Retinopathy/blood , Diabetic Retinopathy/epidemiology , Diabetic Retinopathy/etiology , Female , Male , Cholesterol, HDL/blood , Cross-Sectional Studies , Middle Aged , Retrospective Studies , Nutrition Surveys , Adult , Aged , Risk Factors , United States/epidemiology , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/complications
2.
Ophthalmic Res ; 66(1): 611-619, 2023.
Article in English | MEDLINE | ID: mdl-36682350

ABSTRACT

BACKGROUND: Laser photocoagulation is an effective procedure for the treatment of diabetic macular edema (DME). However, the beneficial effects of conventional laser photocoagulation (CLP) are accompanied by the destruction of retinal photoreceptors. Therefore, subthreshold micropulse laser photocoagulation (SMLP) was proposed for DME. OBJECTIVES: This meta-analysis study was performed to evaluate the efficacy and safety of SMLP compared with CLP for the management of DME. METHODS: The PubMed, Embase, Web of Science, Cochrane, SinoMed, ClinicalTrials.gov, Wanfang, and China National Knowledge Infrastructure (CNKI) databases, published until Dec 2021, were searched to identify studies evaluating the clinical outcomes of SMLP for DME. RESULTS: Eight randomized controlled trials were selected for this meta-analysis involving a total of 546 eyes (275 eyes in SMLP group and 271 eyes in CLP group). SMLP of different wavelengths (577 nm and 810 nm) and duty cycles (5% and 15%) was applied. The pooled outcomes showed that SMLP group, especially 577 nm and 810 nm 15% duty cycle parameter settings, had a statistically significant higher efficacy than CLP group in terms of BCVA (MD = -0.02, 95% CI: -0.03 to -0.01, p < 0.01; MD = -0.09, 95% CI: -0.09 to -0.09, p < 0.01) and showed more significant advantages than CLP group in resolving macular edema assessed by reduction of CMT (MD = -32.87, 95% CI: -37.61 to -28.13, p < 0.01; MD = -8.01, 95% CI: -9.06 to -6.96, p < 0.01), whereas the efficacy of 577 nm and 810 nm 5% duty cycle SMLP subgroups remained numerically superior to CLP group, but nonsignificantly (p > 0.05). In the field of CS, SMLP group (no matter parameter settings) resulted in better preservation of CS compared to CLP group (MD = 1.96, 95% CI: 1.47-2.46, p < 0.01). CONCLUSIONS: Compared with CLP, SMLP may get superior efficacy and safety on improvement of BCVA, reduction of CMT, and preservation of CS. In clinical, SMLP can be considered as a safe and effective therapy in the management of DME.


Subject(s)
Diabetes Mellitus , Diabetic Retinopathy , Macular Edema , Humans , Laser Coagulation/methods , Visual Acuity , Lasers , Treatment Outcome
3.
Cancer Manag Res ; 14: 1825-1833, 2022.
Article in English | MEDLINE | ID: mdl-35652063

ABSTRACT

Purpose: CirRNA F-circEA-2a and miR-3613-3p are two recently identified novel cancer-related RNAs. To date, their participation in colorectal cancer (CRC) is unknown. This research was therefore conducted to analyze their participation in CRC. Patients and Methods: Plasma and paired CRC and non-tumor tissues from CRC patients (n=64) and plasma samples from healthy controls (HCs, n=64) were collected. F-circEA-2a and miR-3613-3p levels in these samples were analyzed using RT-qPCR. The 64 CRC patients were followed up for five years to analyze the prognostic value of plasma F-circEA-2a for CRC. The direct interaction between wild type F-circEA-2a (F-circEA-2a-wt) or mutant F-circEA-2a (F-circEA-2a-mut) and miR-3613-3p was analyzed through RNA-RNA pulldown assay. The role of F-circEA-2a and miR-3613-3p in regulating each other's expression was analyzed through overexpression assay. Their roles in cell proliferation were analyzed using BrdU assay. The role of F-circEA-2a in regulating EZH2 expression was analyzed by RT-qPCR and Western blot. Results: CircEA-2a was overexpressed in CRC, while miR-3613-3p was under-expressed in CRC. Most patients who died during the follow-up had high F-circEA-2a levels. F-circEA-2a-wt, but not F-circEA-2a-mut, directly interacted with miR-3613-3p. F-circEA-2a and miR-3613-3p showed no role in regulating each other's expression. F-circEA-2a reduced the inhibitory effects of miR-3613-3p on cell proliferation. F-circEA-2a upregulated EZH2 at both mRNA and protein levels. Conclusion: F-circEA-2a may suppress the role of miR-3613-3p in CRC by direct sponging and predicts poor survival.

4.
Ecotoxicol Environ Saf ; 216: 112195, 2021 Apr 03.
Article in English | MEDLINE | ID: mdl-33823368

ABSTRACT

Organic fertilizer usage is been introduced into agricultural practices for preventing the damaging effects of chemical fertilizers. Present study investigated the beneficial role of organic fertilizer (nano-vermicompost) on the growth, oxidative stress parameters, antioxidant and nitrogen metabolism, osmolyte accumulation and mineral elements in tomato under drought stress. Drought stress resulted in reduced growth and biomass accumulation by triggering oxidative stress due to excess accumulation of reactive oxygen species (ROS) and reduced mineral uptake. Application of nano-vermicompost proved significantly beneficial in improving growth and mitigating the drought induced growth decline. Nano-vermicompost increased growth and dry matter content and ameliorated the decline in chlorophyll contents, photosynthesis and PSII activity more significantly at higher concentration (100 mg kg-1 soil). ROS accumulation was significantly reduced by nano-vermicompost application thereby enhancing the membrane stability under normal as well as drought conditions. Furthermore, lipid peroxidation and activities of protease and lypoxygenase were significantly reduced. Drought up-regulated antioxidant system and application of nano-vermicompost further enhanced the activities of antioxidant enzymes and the contents of non-enzymatic antioxidant components. Accumulation of osmolytes including proline, glycine betaine and sugars increased significantly due to nano-vermicompost application. Besides, decline in the activity of nitrate reductase and content of essential mineral elements like nitrogen, potassium and phosphorous was also ameliorated by nano-vermicompost application.

5.
Cancer Manag Res ; 13: 3293-3301, 2021.
Article in English | MEDLINE | ID: mdl-33883942

ABSTRACT

INTRODUCTION: The aim of this study was to investigate the role of local radiotherapy in the management of epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancers (NSCLCs) treated with EGFR tyrosine kinase inhibitors (TKIs). MATERIALS AND METHODS: Patients with stage IV EGFR-mutant NSCLC treated with radiotherapy concomitant to EGFR TKIs from May 2010 to December 2017 were retrospectively identified. Overall survival (OS) was the primary endpoints of the study. RESULTS: A total of 205 patients were enrolled in the study. One hundred eleven patients received one-time single-site radiotherapy (SSR), and 94 patients received multiple-site radiotherapy (MSR). Patients who received MSR had longer OS (median OS, 40.0 months; 95% confidence interval [CI], 29.6 to 50.4) than those who received SSR (median OS, 28.9 months; 95% CI, 24.3 to 33.5; P=0.031). Thoracic radiotherapy was associated with prolonged median OS (41.7 months, 95% CI, 29.0 to 54.4 vs 27.1 months, 95% CI 22.7 to 31.5; log-rank P<0.001). Multivariate analysis confirmed that thoracic radiotherapy was independently associated with improved OS (adjusted hazard ratio [HR], 0.514; 95% CI 32.3% to 81.8%; P=0.005). CONCLUSION: MSR improves survival outcomes in patients with advanced-stage, EGFR-mutant, lung adenocarcinoma, with thoracic radiotherapy having the most significant effect on prognosis.

6.
Int J Colorectal Dis ; 36(4): 725-734, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33392665

ABSTRACT

PURPOSE: To determine the effect of transanal total mesorectal excision (taTME) procedure on the postoperative bowel evacuation function of patients with low rectal cancer. METHODS: Bowel evacuation function was investigated in 316 patients with rectal cancer after taTME in 18 hospitals in China. Low anterior resection syndrome (LARS) score, Wexner score, and EORTC QLQ-C30 were used for functional evaluation. The association between perioperative risk factors and LARS score was determined by univariate and multivariate analyses. RESULTS: The prevalence rate of no LARS, minor LARS, and major LARS in patients after taTME was 39.9%, 28.2%, and 31.9%, respectively. The two most frequently reported symptoms of LARS after taTME were bowel clustering (72.8%) and fecal urgency (63.3%). Patients with major LARS had significantly higher Wexner score and worse global health status and financial difficulties according to the EORTC QLQ-C30 questionnaire than those without major LARS. Preoperative chemoradiotherapy was an independent risk factor of major LARS occurrence after taTME (OR: 3.503, P = 0.044); existing preoperative constipation (OR: 0.082, P = 0.040) and manual anastomosis (OR: 4.536, P = 0.021) were favorable factors affecting bowel evacuatory function within 12 months after taTME, but for patients whose follow-up time was longer than 12 months, postoperative chemoradiotherapy (OR: 8.790, P = 0.001) and defunctioning stoma (OR: 3.962, P = 0.010) were independent risk factors. CONCLUSIONS: The bowel evacuation function after taTME is acceptable. Perioperative chemoradiotherapy, anastomotic method, and preoperative constipation are factors associated with bowel dysfunction after taTME.


Subject(s)
Laparoscopy , Rectal Neoplasms , Transanal Endoscopic Surgery , China , Humans , Postoperative Complications/etiology , Rectal Neoplasms/surgery , Rectum/surgery , Syndrome , Transanal Endoscopic Surgery/adverse effects
7.
Int Immunol ; 33(5): 261-272, 2021 04 22.
Article in English | MEDLINE | ID: mdl-33258927

ABSTRACT

BACKGROUND: We previously found two distinct passenger dendritic cell (DC) subsets in the rat liver that played a central role in the liver transplant rejection. In addition, a tolerance-inducing protocol, donor-specific transfusion (DST), triggered systemic polytopical production of depleting alloantibodies to donor class I MHC (MHCI) antigen (DST-antibodies). METHODS: We examined the role of DST-antibodies in the trafficking of graft DC subsets and the alloresponses in a rat model. We also examined an anti-donor class II MHC (MHCII) antibody that recognizes donor DCs more selectively. RESULTS: Preoperative transfer of DST-antibodies or DST pretreatment eliminated all passenger leukocytes, including both DC subsets and depleted the sessile DCs in the graft to ~20% of control. The CD172a+CD11b/c+ immunogenic subset was almost abolished. The intrahost direct or semi-direct allorecognition pathway was successfully blocked, leading to a significant suppression of the CD8+ T-cell response in the recipient lymphoid organs and the graft with delayed graft rejection. Anti-donor MHCII antibody had similar effects without temporary graft damage. Although DST pretreatment had a priming effect on the proliferative response of recipient regulatory T cells, DST-primed sera and the anti-donor MHCII antibody did not. CONCLUSION: DST-antibodies and anti-donor MHCII antibodies could suppress the CD8+ T-cell-mediated liver transplant rejection by depleting donor immunogenic DCs, blocking the direct or semi-direct pathways of allorecognition. Donor MHCII-specific antibodies may be applicable as a selective suppressant of anti-donor immunity for clinical liver transplantation without the cellular damage of donor MHCII- graft cells and recipient cells.


Subject(s)
Dendritic Cells/immunology , Graft Rejection/immunology , Histocompatibility Antigens Class I/immunology , Isoantibodies/immunology , Animals , Animals, Genetically Modified/immunology , Antibody Formation/immunology , Antigens, Differentiation/immunology , CD11b Antigen/immunology , CD8-Positive T-Lymphocytes , Graft Survival/immunology , Immune Tolerance/immunology , Liver Transplantation/methods , Rats , Rats, Inbred Lew , T-Lymphocytes, Regulatory/immunology , Tissue Donors , Transplantation, Homologous/methods
8.
Kaohsiung J Med Sci ; 37(2): 111-120, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33021020

ABSTRACT

Gastric cancer is one of the most common cancers globally and has a poor prognosis. MiR-936 has been reported to regulate cell activity and tumor progression in non-small cell lung cancer, glioma, and epithelial ovarian cancer. However, the specific role and mechanism of miR-936 in gastric cancer have not been explored. In present study, gastric cancer cells were transfected with miR-936 mimic, and cell proliferation, cell cycle distribution, cell apoptosis, migration and invasion were assessed via cell-counting kit-8, flow cytometry, wound healing, and transwell assay, respectively. Dual luciferase reporter assay was used to check miR-936 binding to its downstream target. It was shown that miR-936 was downregulated in gastric cancer tissues and cells. Erb-B2 Receptor Tyrosine Kinase 4 (ERBB4) was confirmed as a direct target of miR-936 and negatively regulated its expression by miR-936. Overexpression of miR-936 suppressed cell proliferation, cell cycle progression, cell migration and invasion, and enhanced cell apoptosis in gastric cancer cells, which could be reversed by further ERBB4 overexpression. Western blot results showed that miR-936/ERBB4 axis regulated Akt-related pathways to control gastric cancer cell activities. Therefore, our data suggest that miR-936 overexpression inhibits cell proliferation and invasion and promotes cell apoptosis through Akt-related pathways by targeting ERBB4, which provides novel insight to target miR-936 or miR-936/ERBB4 axis for the treatment of gastric cancer.


Subject(s)
Cell Movement/genetics , MicroRNAs/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Receptor, ErbB-4/metabolism , Signal Transduction , Stomach Neoplasms/genetics , Stomach Neoplasms/pathology , Apoptosis/genetics , Base Sequence , Cell Line, Tumor , Cell Proliferation/genetics , Down-Regulation/genetics , Gene Expression Regulation, Neoplastic , Humans , MicroRNAs/genetics , Neoplasm Invasiveness , Up-Regulation/genetics
9.
Ann Palliat Med ; 9(4): 2003-2012, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32692247

ABSTRACT

BACKGROUND: To study the effects and adverse reactions of different doses and fractionated radiotherapies on non-epidermal growth factor receptor (EGFR) mutant lung adenocarcinoma patients with multiple brain metastases. METHODS: In total, 80 patients eligible for inclusion were randomly divided into 4 groups. Group A included whole brain radiotherapy (WBRT) alone 300 cGy/fraction ×10 fractions, at a total dose of 3,000 cGy. Group B included WBRT alone 180 cGy/fraction ×22 fractions, at a total dose of 3,960 cGy. Group C included intracranial metastases radiotherapy alone 250 cGy/fraction ×22 fractions at a total dose of 5,500 cGy. Group D included the whole brain + intracranial metastases group (SIB group) whole brain 180 cGy/fraction ×22 fractions intracranial metastases 250 cGy/fraction ×22 fractions, at a total dose 3,960 cGy, 5,500 cGy, respectively. RESULTS: The median survival time of intracranial disease-free survival (IPFS) in group A, group B, group C, and group D was 6, 9, 8, and 13 months, respectively (P=0.000). The median overall survival (OS) time was 16, 24.5, 24, and 30 months, respectively (P=0.150). There was a significant difference in IPFS between different doses and fractionated radiotherapies, but there was no difference in OS. Multivariate analysis showed that the radiotherapy dose of intracranial metastases was positively correlated with IPFS and OS. The incidence rate of adverse reaction of memory decline in 0.5, 1, and 2 years in group A, group B, group C, and group D was respectively 10.0%, 15.0%, 5.0%, and 15.0% (P=0.006); 20.0%, 45.0%, 30.0%, and 60.0% (P=0.000); 10.0%, 20.0%, 35.0%, and 65.0% (P=0.000). The incidence rates of memory decline in the groups of WBRT were significantly more increased than in the non-WBRT group. CONCLUSIONS: Radiotherapy is effective for multiple brain metastases of lung adenocarcinoma, the increase of radiotherapy dose can improve IPFS and OS, and the adverse reaction of memory decline after WBRT is increased but tolerable. Therefore, WBRT and simultaneous integrated boost (SIB) radiotherapy of intracranial metastases is recommended for multiple brain metastases of non-EGFR-mutant lung adenocarcinoma.


Subject(s)
Brain Neoplasms , Lung Neoplasms , Adenocarcinoma of Lung , Brain Neoplasms/radiotherapy , Combined Modality Therapy , Cranial Irradiation , Dose Fractionation, Radiation , Humans , Lung Neoplasms/radiotherapy
10.
Ying Yong Sheng Tai Xue Bao ; 30(10): 3501-3508, 2019 Oct.
Article in Chinese | MEDLINE | ID: mdl-31621237

ABSTRACT

The effects of inoculation of rhizosphere-promoting bacteria (PGPR) on photosynthesis and physiological-ecological characteristics of apple tree seedlings under drought conditions were investigated in this study, aiming to provide a theoretical basis for the application of PGPR in plant drought resistance. In the pot experiment, the rhizosphere-promoting bacterium YX2 which had both ACC deaminase activity and strong phosphorus solubilizing ability was selected as the tested strain. Apple seedlings were grown under four different irrigation levels i.e., control (CK), mild drought (LD), moderate drought (MD), and severe drought (SD) with soil moisture equivalent to 70%-80%, 55%-65%, 40%-50% and 25%-35% of field water holding capacity, respectively. Inoculation of PGPR alleviated the damaging effects of drought on growth by improving relative water content and chlorophyll content in apple tree seedlings. In addition, PGPR inoculated individuals exhibited higher antioxidant enzyme activity, chlorophyll fluorescence values, stomatal conductance and photosynthetic rate and lower relative conductivity and lipid peroxidation. Our results suggested that PGPR-YX2 alleviated the negative effects of drought stress on the growth and net photosynthetic rate by improving the antioxidant system, water content and membrane functioning.


Subject(s)
Droughts , Malus , Photosynthesis , Seedlings , Soil , Water
11.
Hernia ; 23(6): 1155-1161, 2019 12.
Article in English | MEDLINE | ID: mdl-31172320

ABSTRACT

PURPOSE: Inguinal hernias are the most common type of abdominal wall hernias. Although surgery is the only effective treatment for these hernias in adults, several problems associated with surgical treatment have been reported. If the hernia exits from a weak point of the abdominal wall, it can obstruct the bowel, thereby causing serious complications, including intestinal obstruction or strangulation. Through this study, we aimed to analyze the optimal incarceration induction time taken to cause some degree of necrosis from which recovery would be possible in a rat incarcerated abdominal wall hernia model and to determine the efficacy of heparin for expedite recovery from intestinal incarceration. METHODS: A rat incarcerated abdominal wall hernia model was constructed, intestinal activity and the incarceration induction time were determined based on the color of the intestine and HE staining of intestinal sections. Heparin and procaine were sprayed onto intestinal surfaces, and their effects on the recovery from intestinal incarceration were evaluated. RESULTS: Recovery from intestinal incarceration would be better if the incarceration induction time was maintained below 2.5 h in our rat model, and heparin was found to be superior to procaine in the expedite recovery from intestinal incarceration, particularly immediately after relieving such intestines. CONCLUSIONS: The results of this study are significant for planning the treatment of incarcerated inguinal hernia. Further, heparin is superior to procaine in terms of expedite recovery from intestinal incarceration.


Subject(s)
Cardiovascular Agents/pharmacology , Heparin/pharmacology , Hernia, Abdominal/surgery , Intestinal Obstruction/surgery , Intestines/drug effects , Procaine/pharmacology , Animals , Cardiovascular Agents/administration & dosage , Disease Models, Animal , Heparin/administration & dosage , Hernia, Abdominal/complications , Intestinal Obstruction/etiology , Intestines/blood supply , Intestines/pathology , Intestines/surgery , Male , Necrosis/etiology , Necrosis/prevention & control , Procaine/administration & dosage , Rats , Rats, Sprague-Dawley , Recovery of Function , Time Factors
12.
RSC Adv ; 9(5): 2559-2566, 2019 Jan 18.
Article in English | MEDLINE | ID: mdl-35520519

ABSTRACT

The development of hollow ferrogadolinium nanonetworks has not been reported for nanomedicine application until now. In this study, we developed a hollow and porous ferrogadolinium nanonetwork structure using the one-pot solvothermal method. This nanoparticle could be simultaneously used as a T 1 and T 2 dual-modal magnetic resonance imaging (MRI) contrast agent. In addition, the hollow lumen and abundant pores of the nanonetworks maximized the loading capacity and conferred the nanoplatforms for suitable anticancer drug loading capacity. Using these nanonetworks, MRI and anticancer experiments were conducted in vitro and satisfactory dual-modal MRI and cancer chemotherapy results were obtained. Therefore, the nanonetworks with dual-modal MRI and drug loading abilities effectively complement the ferrogadolinium composites' library and hold great promise in nanomedicine for simultaneous cancer diagnosis and chemotherapy.

13.
RSC Adv ; 9(13): 7277, 2019 Mar 01.
Article in English | MEDLINE | ID: mdl-35532528

ABSTRACT

[This corrects the article DOI: 10.1039/C8RA09102A.].

14.
Surg Innov ; 26(2): 260-264, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30565514

ABSTRACT

Superior mesenteric artery (SMA) aneurysm is the third most common splanchnic artery aneurysm. A 73-year-old woman presented with a minimally symptomatic SMA aneurysm, which was resected by laparoscopic surgical technique. The patient recovered quickly and remained well after 8 months of follow-up. This case report and literature review presents a rare mycotic aneurysm that developed in the SMA. Laparoscopic surgery can be a useful technique for the treatment of mycotic SMA aneurysms.


Subject(s)
Aneurysm, Infected , Mesenteric Artery, Superior , Abdomen/diagnostic imaging , Abdomen/surgery , Aged , Aneurysm, Infected/diagnostic imaging , Aneurysm, Infected/surgery , Female , Humans , Mesenteric Artery, Superior/diagnostic imaging , Mesenteric Artery, Superior/surgery , Tomography, X-Ray Computed
15.
Int Immunol ; 30(1): 23-33, 2018 02 03.
Article in English | MEDLINE | ID: mdl-29365122

ABSTRACT

Naive lymphocytes systemically recirculate for immunosurveillance inspecting foreign antigens and pathogens in the body. Trafficking behavior such as the migration pathway and transit time within the gastrointestinal tract, however, remains to be elucidated. Rat thoracic duct lymphocytes (TDLs) were transferred to a congeneic host that had undergone mesenteric lymphadenectomy. The migration pathway was investigated using newly developed four-color immunohistochemistry and immunofluorescence. Donor TDLs showed rapid transition in gut tissues from which they emerged in mesenteric lymph around 4 h after intravenous injection. Immunohistochemistry showed that donor TDLs predominantly transmigrated across high endothelial venules (HEVs) at the interfollicular area of the Peyer's patches (PPs), then exited into the LYVE-1+ efferent lymphatics, that were close to the venules. The rapid recirculation depended largely on the local expression of unsulfated sialyl-Lewis X on these venules where putative dendritic cells (DCs) were associated underneath. Recruited naive T cells briefly made contact with resident DCs before exiting to the lymphatics in the steady state. In some transplant settings, however, the T cells retained contact with DCs and were sensitized and differentiated into activated T cells. In conclusion, we directly demonstrated that lymphocyte recirculation within the gut is a very rapid process. The interfollicular area of PPs functions as a strategically central site for rapid immunosurveillance where HEVs, efferent lymphatics and resident DCs converge. PPs can, however, generate alloreactive T cells, leading to exacerbation of graft-versus-host disease or gut allograft rejection.


Subject(s)
Endothelium/immunology , Immunologic Surveillance/immunology , Intestines/immunology , Lymphocytes/immunology , Oligosaccharides/immunology , Peyer's Patches/immunology , Animals , Blood Circulation , Cell Line, Tumor , Lymphocytes/pathology , Mice , Rats , Rats, Inbred Strains , Sialyl Lewis X Antigen
16.
J Gastroenterol ; 51(10): 985-98, 2016 Oct.
Article in English | MEDLINE | ID: mdl-26891909

ABSTRACT

BACKGROUND: Lymphocyte recruitment into the portal tract is crucial not only for homeostatic immune surveillance but also for many liver diseases. However, the exact route of entry for lymphocytes into portal tract is still obscure. We investigated this question using a rat hepatic allograft rejection model. METHODS: A migration route was analyzed by immunohistological methods including a recently developed scanning electron microscopy method. Transmigration-associated molecules such as selectins, integrins, and chemokines and their receptors expressed by hepatic vessels and recruited T-cells were analyzed by immunohistochemistry and flow cytometry. RESULTS: The immunoelectron microscopic analysis clearly showed CD8ß(+) cells passing through the portal vein (PV) endothelia. Furthermore, the migrating pathway seemed to pass through the endothelial cell body. Local vascular cell adhesion molecule-1 (VCAM-1) expression was induced in PV endothelial cells from day 2 after liver transplantation. Although intercellular adhesion molecule-1 (ICAM-1) expression was also upregulated, it was restricted to sinusoidal endothelia. Recipient T-cells in the graft perfusate were CD25(+)CD44(+)ICAM-1(+)CXCR3(+)CCR5(-) and upregulated α4ß1 or αLß2 integrins. Immunohistochemistry showed the expression of CXCL10 in donor MHCII(high) cells in the portal tract as well as endothelial walls of PV. CONCLUSIONS: We show for the first time direct evidence of T-cell transmigration across PV endothelial cells during hepatic allograft rejection. Interactions between VCAM-1 on endothelia and α4ß1 integrin on recipient effector T-cells putatively play critical roles in adhesion and transmigration through endothelia. A chemokine axis of CXCL10 and CXCR3 also may be involved.


Subject(s)
CD8-Positive T-Lymphocytes/physiology , Graft Rejection/immunology , Liver Transplantation/adverse effects , Transendothelial and Transepithelial Migration , Allografts/immunology , Animals , CD8-Positive T-Lymphocytes/chemistry , Chemokine CXCL10/analysis , Endothelium/chemistry , Endothelium/metabolism , Hyaluronan Receptors/analysis , Immunohistochemistry , Integrin alpha4beta1/metabolism , Intercellular Adhesion Molecule-1/analysis , Intercellular Adhesion Molecule-1/metabolism , Interleukin-2 Receptor alpha Subunit/analysis , Lymphocyte Function-Associated Antigen-1/metabolism , Male , Microscopy, Electron, Scanning , Portal Vein , Rats, Inbred ACI , Rats, Inbred Lew , Receptors, CCR5/analysis , Receptors, CXCR3/analysis , Up-Regulation , Vascular Cell Adhesion Molecule-1/metabolism
17.
Mol Biol Rep ; 41(7): 4493-505, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24623407

ABSTRACT

Pathological neovascularization are the most prevalent causes of moderate or severe vision loss. Long non-coding RNAs (lncRNAs) have emerged as a novel class of regulatory molecules involved in numerous biological processes and complicated diseases. However, the role of lncRNAs in ocular neovascularization is still unclear. Here, we constructed a murine model of ocular neovascularization, and determined lncRNA expression profiles using microarray analysis. We identified 326 or 51 lncRNAs that were significantly either up-regulated or down-regulated in the vaso-obliteration or neovascularization phase, respectively. Based on Pearson correlation analysis, lncRNAs/mRNAs co-expression networks were constructed. GO enrichment analysis of lncRNAs-co-expressed mRNAs indicated that the biological modules were correlated with chromosome organization, extracellular region and guanylate cyclase activator activity in the vaso-obliteration phase, and correlated with cell proliferation, extracellular region and guanylate cyclase regulator activity in the neovascularization phase. KEGG pathway analysis indicated that MAPK signaling was the most significantly enriched pathway in both phases. Importantly, Vax2os1 and Vax2os2 were not only dynamically expressed in the vaso-obliteration and neovascularization phases, but also significantly altered in the aqueous humor of patients with neovascular age-related macular degeneration (AMD), suggesting a potential role of lncRNAs in the regulation of ocular neovascularization. Taken together, this study provided novel insights into the molecular pathogenesis of ocular neovascularization. The intervention of dysregulated lncRNA could become a potential target for the prevention and treatment of ocular vascular diseases.


Subject(s)
Hyperoxia/genetics , Macular Degeneration/genetics , Neovascularization, Pathologic/genetics , RNA, Long Noncoding/metabolism , RNA, Messenger/genetics , Retina/metabolism , Aged , Animals , Aqueous Humor/metabolism , Female , Gene Expression Profiling , Gene Expression Regulation , Gene Regulatory Networks , Guanylate Cyclase-Activating Proteins/genetics , Guanylate Cyclase-Activating Proteins/metabolism , Homeodomain Proteins/genetics , Homeodomain Proteins/metabolism , Humans , Hyperoxia/metabolism , Hyperoxia/pathology , MAP Kinase Signaling System , Macular Degeneration/metabolism , Macular Degeneration/pathology , Male , Mice , Middle Aged , Neovascularization, Pathologic/metabolism , Neovascularization, Pathologic/pathology , Oligonucleotide Array Sequence Analysis , Protein Isoforms/genetics , Protein Isoforms/metabolism , RNA, Long Noncoding/genetics , RNA, Messenger/metabolism , Retina/pathology
18.
Ultramicroscopy ; 109(11): 1326-32, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19577845

ABSTRACT

With a steady temperature increase under high vacuum (HV) in an environmental scanning electronic microscope, we observed charge-free characterization and fine secondary electron (SE) images in focus for insulating ceramics (alumina (Al2O3), aluminum nitride (AlN), pure magnesium silicate (Mg2SiO4)). The sample current I(sc) increased from -8.18 x 10(-13) to 2.76 x 10(-7)A for Al2O3 and -9.28 x 10(-12) to 2.77 x 10(-6)A for AlN with the temperature increased from 298 to 633K. The surface conductance sigma increased from 5.6 x 10(-13) to 5.0 x 10(-11)/Omega for Al2O3 and 1.1 x 10(-12) to 1.0 x 10(-7)/Omega for AlN with the temperature increased from 363 to 593K. The SE image contrast obtained via heating approach in high vacuum with an Everhart-Thornley SE-detector was better than that via conventional approach of electron-ion neutralization in low vacuum (LV) with a gaseous SE-detector. The differences of compensation temperatures for charge effects indicate dielectric and thermal properties, and band structures of insulators. The charge compensation mechanisms of heating approach mainly relate to accelerated release of trapped electrons on insulating surface and to increase of electron emission yield by heating.

19.
Int Immunol ; 20(3): 385-94, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18303011

ABSTRACT

The existence of donor effector cell subsets responsible for either gut or skin graft-versus-host disease (GvHD) is still undetermined. We examined the trafficking and role of donor CD8(+) intra-epithelial lymphocytes (IELs) in the gut and skin epithelia concerning alpha E beta 7 integrin (CD103) expression, using a rat acute lethal GvHD model. Most CD103(+) donor cells were CD8(+) and showed a proliferative activity in the target epithelia. On the other hand, activated donor T cells in the host lymphoid tissues did not express CD103, indicating the presence of CD8(+) IEL precursors in the lymphoid tissues that may up-regulate CD103 only after migrating to the target organs. At the late stage of GvHD, while >80% of the donor CD8(+) IELs were CD103(+) in the gut epithelium, both CD4(+) and CD103(+)CD8(+) T cells evenly accumulated in the skin epidermis. The CD103 expression by donor CD8(+) IELs especially in the gut was also correlated with the clinical GvHD manifestations. Furthermore, the selective removal of gut lymph nodes (LNs) but not skin LNs suppressed the infiltration of CD103(+) donor IELs in the gut and alleviated intestinal GvHD. In conclusion, CD103(+)CD8(+) donor T cells predominantly infiltrate into the gut epithelium and are responsible for the manifestations of intestinal GvHD. This pathology is at least partly dependent on the gut LNs.


Subject(s)
Antigens, CD/immunology , CD8-Positive T-Lymphocytes/physiology , Cell Movement/physiology , Graft vs Host Disease/immunology , Integrin alpha Chains/immunology , Intestinal Mucosa/immunology , Lymph Nodes/immunology , Animals , Antigens, CD/metabolism , Cell Proliferation , Disease Models, Animal , Gene Expression Regulation , Graft vs Host Disease/pathology , Integrin alpha Chains/metabolism , Intestinal Mucosa/pathology , Intestinal Mucosa/radiation effects , Lymphoid Tissue/radiation effects , Male , Rats , Time Factors
20.
Liver Int ; 28(3): 319-30, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18290774

ABSTRACT

BACKGROUND: We have investigated how recirculating lymphocytes patrol the liver in a normal steady state. METHODS: Thoracic duct lymphocytes of congeneic rats were intravenously transferred to host rats and donor cell trafficking in the liver and hepatic lymph was examined. Host hepatic lymph nodes (HLNs) were selectively removed, which allowed liver-derived donor cells to collect in the thoracic duct without transit in the intervening HLNs. RESULTS: The number of donor cells in the thoracic duct lymph significantly increased over the baseline 3, 5 and 11 h after transfer in the HLN-removed, non-pretreated, and HLN-ligated (in which a lymph efflux was blocked) groups, respectively. Histologically, donor cells appeared in the portal area from 0.5 h after transfer and frequently attached to the basal lamina of portal vein both externally and internally. Three hours after transfer, a few donor cells appeared in the subcapsular sinus of HLNs. CONCLUSION: The minimal transit time of rat recirculating lymphocytes is 3-4 h in the liver and 5-8 h in the hepatic LNs, in a normal steady state. Recirculating lymphocytes might transmigrate through the portal vein as well as the sinusoid in the periportal zone. This rapid transit might enable an efficient surveillance of the liver portal area by the recirculating lymphocytes.


Subject(s)
Cell Movement/immunology , Liver/immunology , Lymph/cytology , Lymphocytes/immunology , Thoracic Duct/immunology , Animals , Flow Cytometry , Immunohistochemistry , Kinetics , Lymph/immunology , Lymph Node Excision , Lymphocyte Transfusion , Lymphocytes/ultrastructure , Microscopy, Electron, Scanning , Rats , Statistics, Nonparametric , Time Factors
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