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1.
Liver Int ; 43(5): 1021-1034, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36912786

RESUMO

BACKGROUND & AIMS: Nonalcoholic steatohepatitis (NASH), a more severe subtype of nonalcoholic fatty liver disease, can cause cirrhosis and hepatocellular carcinoma. Macrophages play critical roles in initiating and maintaining NASH-induced liver inflammation and fibrosis. However, the underlying molecular mechanism of macrophage chaperone-mediated autophagy (CMA) in NASH remains unclear. We aimed to investigate the effects of macrophage-specific CMA on liver inflammation and identify a potential therapeutic target for NASH treatment. METHODS: The CMA function of liver macrophages was detected using Western blot, quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and flow cytometry. By constructing myeloid-specific CMA deficiency mice, we evaluated the effects of deficient CMA of macrophages on monocyte recruitment, liver injury, steatosis and fibrosis in NASH mice. A label-free mass spectrometry was utilized to screen the substrates of CMA in macrophages and their mutual interactions. The association between CMA and its substrate was further examined by immunoprecipitation, Western blot and RT-qPCR. RESULTS: A typical hallmark in murine NASH models was impaired CMA function in hepatic macrophages. Monocyte-derived macrophages (MDM) were the dominant macrophage population in NASH, and CMA function was impaired in MDM. CMA dysfunction aggravated liver-targeted recruitment of monocyte and promoted steatosis and fibrosis. Mechanistically, Nup85 functions as a substrate for CMA and its degradation was inhibited in CMA-deficient macrophages. Inhibition of Nup85 attenuated the steatosis and monocyte recruitment caused by CMA deficiency in NASH mice. CONCLUSIONS: We proposed that the impaired CMA-induced Nup85 degradation aggravated monocyte recruitment, promoting liver inflammation and disease progression of NASH.


Assuntos
Autofagia Mediada por Chaperonas , Hepatopatia Gordurosa não Alcoólica , Complexo de Proteínas Formadoras de Poros Nucleares , Animais , Camundongos , Modelos Animais de Doenças , Fibrose , Inflamação/patologia , Fígado/patologia , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/patologia , Complexo de Proteínas Formadoras de Poros Nucleares/metabolismo
2.
Zhonghua Yi Xue Za Zhi ; 102(31): 2465-2469, 2022 Aug 23.
Artigo em Chinês | MEDLINE | ID: mdl-36000377

RESUMO

Objective: To evaluate the related factors of postoperative recurrence intrigeminal neuralgia (TN) patients treated with fully neuroendoscopic microvascular decompression (MVD). Methods: The clinical baseline data and preoperative MRI imaging data of 112 patients with TN treated by neuroendoscopic MVD from December 2008 to December 2020 in the Department of Neurosurgery, Beijing Shijitan Hospital Affiliated to Capital Medical University were retrospectively analyzed, including: area ratio of cerebellopontine area (CPA)(healthy side/affected side), trigeminal nerve(TGN)length ratio(healthy side/affected side), TGN angle ratio(healthy side/affected side), and criminal vessel type. Multivariate Cox proportional hazards model was used to analyze the factors affecting postoperative recurrence. Results: Among the 112 patients in this group, there were 49 males and 63 females. The age ranged from 20 to 82 (59±9) years, and the course of disease was 0.05 to 30.00 (5.60±5.15) years. Pain was located on the left side in 43 cases (38.39%) and on the right side in 69 cases (61.61%), respectively. All patients were followed up for more than 1 year, with an average follow-up time of 21.5 months, and 11 cases recurred. Multivariate Cox regression analysis revealed that disease duration≥3 years(HR=9.34, 95%CI:1.12-39.07), CPA area ratio(healthy side/affected side)>1 (HR=27.47, 95%CI:1.69-44.20), criminal vessel type with vein(HR=35.39, 95%CI:1.26-18.60) and criminal vessel type with arteriovenous (HR=46.07, 95%CI: 2.74-27.75) were the main factors influencing recurrence of MVD surgery (all P<0.05). Conclusion: The disease duration≥3 years, CPA area ratio(healthy side/affected side)>1, and criminal vessel type with vein/arteriovenous are the relevant factors that affect the recurrence rate after the fully neuroendoscopic MVD treatment for trigeminal neuralgia.


Assuntos
Cirurgia de Descompressão Microvascular , Complicações Pós-Operatórias , Neuralgia do Trigêmeo , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Cirurgia de Descompressão Microvascular/efeitos adversos , Pessoa de Meia-Idade , Dor/etiologia , Recidiva , Estudos Retrospectivos , Resultado do Tratamento , Nervo Trigêmeo/cirurgia , Neuralgia do Trigêmeo/cirurgia , Adulto Jovem
3.
BJOG ; 128(5): 890-898, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32930483

RESUMO

OBJECTIVE: To evaluate the clinical diagnostic validity of carbon nanoparticle suspension (CNS) in sentinel lymph node biopsy (SLNB) for assessing lymphatic spread of early-stage cervical cancer. DESIGN: A prospective study. SETTING AND POPULATION: 356 cases. METHODS: We enrolled 356 stage Ia2-IIa2 cervical cancer patients to undergo SLNB using CNS, followed by systematic pelvic lymphadenectomy. All lymph node specimens were assessed using conventional histopathologic ± pathologic ultrastaging analyses. MAIN OUTCOME MEASURES: Sentinel lymph node detection rate (DR), clinical diagnostic validity and various related factors were analysed. RESULTS: CNS identified 1456 SLNs in 325 patients. The overall SLN DR was 91.29%. A significantly higher DR was found for patients with tumours <20 mm (97.75% versus 71.91%; P < 0.001). Two patients had false-negative results. SLNB with CNS had sensitivity of 96.65%, false-negative rate (FNR) of 4.35% and negative predictive value (NPV) of 99.29%. Importantly, sensitivity (100%), NPV (100%) and FNR (0%) were improved when testing the subgroup of patients with tumours <20 mm (267 cases). There were no observed differences in DR based on pathological type or grade, stage, depth of stromal invasion, surgical approach, menopausal status or prior treatment with chemotherapy (P > 0.05). CONCLUSIONS: Sentinel lymph node biopsy with CNS results in favourable DR, sensitivity and NPV for women with early-stage cervical cancer with small tumour sizes. SLNB with CNS is safe, feasible and relatively effective for guiding precise surgical treatment of early-stage cervical cancer. TWEETABLE ABSTRACT: Sentinel lymph node biopsy with carbon nanoparticle suspension is safe and feasible for early-stage cervical cancer.


Assuntos
Adenocarcinoma/patologia , Carbono , Carcinoma de Células Escamosas/patologia , Linfonodos/patologia , Nanopartículas , Biópsia de Linfonodo Sentinela/métodos , Neoplasias do Colo do Útero/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Carcinoma de Células Escamosas/cirurgia , Feminino , Humanos , Modelos Logísticos , Excisão de Linfonodo , Linfonodos/cirurgia , Metástase Linfática , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pelve , Estudos Prospectivos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Suspensões , Neoplasias do Colo do Útero/cirurgia , Adulto Jovem
4.
Scand J Immunol ; 93(3): e12996, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33205443

RESUMO

Intestinal T cells form a central part of the front-line defence against foreign organisms and need to be situated in the mucosa where infection occurs. It is well accepted that immunization by a mucosal route favours localization of antigen-specific effector T cells in the mucosal epithelium, while systemic immunization does not. The aim of the study is to determine how homing receptors are specifically involved in retaining effector T cells in the small intestine after oral immunization. We here demonstrate that the chemokine receptor CXCR6, integrins ß7 and CD29 contribute differentially to the epithelial retention phenotype of CD8+ T cells in the small intestine of mice. CD8+ intraepithelial lymphocytes (IELs) of unvaccinated mice are predominantly ß7 single positives, and subcutaneous immunization-induced antigen-specific CD8+ effector IELs are mainly composed of CXCR6+ , CD29+ and CXCR6+ CD29+ cells. Strikingly, the majority of oral immunization-induced antigen-specific CD8+ effector IELs exhibit a distinct, tissue-specific CXCR6+ ß7+ double-positive phenotype, cytotoxic potential and enhanced intraepithelial localization. Transfer of antigen-specific CD8+ T cells preactivated with certain immuno-stimuli (such as monophosphoryl lipid A) results in increased accumulation of donor IELs with the CXCR6+ ß7+ phenotype. As ß7 exclusively paired with αE on IELs, our results strongly suggest that CXCR6 may cooperate with the heterodimer αEß7 to preferentially retain intestinally induced effector IELs in the epithelium. The identification of this novel IEL phenotype has significant implications for the development of vaccines and therapeutic strategies to enhance gut immunity.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Cadeias beta de Integrinas/metabolismo , Intestino Delgado/imunologia , Linfócitos Intraepiteliais/imunologia , Receptores CXCR6/metabolismo , Transferência Adotiva , Animais , Linfócitos T CD8-Positivos/transplante , Integrina beta1/metabolismo , Mucosa Intestinal/citologia , Mucosa Intestinal/imunologia , Intestino Delgado/citologia , Linfócitos Intraepiteliais/transplante , Listeria monocytogenes/imunologia , Ativação Linfocitária/imunologia , Subpopulações de Linfócitos/imunologia , Subpopulações de Linfócitos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Vacinação
5.
Zhonghua Xin Xue Guan Bing Za Zhi ; 48(9): 753-758, 2020 Sep 24.
Artigo em Chinês | MEDLINE | ID: mdl-32957758

RESUMO

Objective: To investigate the clinical value of left ventricular function assessment in patients with cardiovascular disease by fully automatic quantified three-dimensional transthoracic echocardiography. Methods: One hundred and ninety-seven patients with cardiac diseases were examined by three-dimensional transthoracic echocardiography from September 2017 to May 2019. Data from 61 patients with grade 1 echocardiographic image quality were used to determine the default boundary values of endocardial end-diastolic and end-systolic phases. Clinical features were analyzed based on electronic medical records. The accuracy and repeatability of this strategy was evaluated by comparing left ventricular end-diastolic volume (LVEDV), end-systolic volume (LVESV) and left ventricular ejection fraction (LVEF) measured by automated quantitative three-dimensional echocardiography and those measured by conventional manual transthoracic echocardiography, the latter served as gold standard. Results: The levels of LVEDV, LVESV and LVEF measured by automatic three-dimensional echocardiography were positively correlated with values obtained by manual measurement(r=0.97,0.97, 0.98, 0.97, 0.97, 0.96;P<0.05). The levels of LVEDV and LVESV measured by full-automatic three-dimensional echocardiography were significantly higher than those obtained by manual three-dimensional echocardiography(all P<0.05). The classification and correlation of systolic dysfunction in patients with abnormal ventricular wall motion by automatic three-dimensional echocardiography were significantly improved after manual calibration (κ=0.74, P=0.00) as compared to without manual calibration (κ=0.63, P=0.00). The inter-observer and intra-observer variability of fully automated three-dimensional echocardiography were significantly smaller than manual three-dimensional echocardiography(both P<0.05). Conclusion: Fully automatic quantified three-dimensional transthoracic echocardiography possesses excellent accuracy and repeatability in measuring left ventricular volume and function, and it is feasible for clinical application.


Assuntos
Doenças Cardiovasculares , Ecocardiografia Tridimensional , Ecocardiografia , Estudos de Viabilidade , Humanos , Volume Sistólico , Função Ventricular Esquerda
6.
Liver Int ; 40(10): 2427-2438, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32339374

RESUMO

BACKGROUND & AIMS: The pathological hallmark of nonalcoholic fatty liver disease (NAFLD) is an imbalance in hepatic lipid homeostasis, in which lipophagy has been found to play a vital role. However, the underlying molecular mechanisms remain unclear. We investigated the role of chaperone-mediated autophagy (CMA) in the pathogenesis of NAFLD. METHODS: CMA activity was evaluated in liver tissues from NAFLD patients and high-fat diet (HFD)-fed mice. Liver-specific LAMP2A-knockout mice and HepG2 cells lacking LAMP2A [L2A(-) cells] were used to investigate the influence of CMA on lipolysis in hepatocytes. The expression of Plin5, a lipid droplet (LD)-related protein, was also evaluated in human and mouse liver tissues and in [L2A(-)] cells. RESULTS: Here, we found disrupted CMA function in the livers of NAFLD patients and animal models, displaying obvious reduction of LAMP2A and concurrent with decreased levels of CMA-positive regulators. More LDs and higher serum triglycerides accumulated in liver-specific LAMP2A-knockout mice and L2A(-) cells under high-fat challenge. Meanwhile, deleting LAMP2A hindered LD breakdown but not increased LD formation. In addition, the LD-associated protein Plin5 is a CMA substrate, and its degradation through CMA is required for LD breakdown. CONCLUSIONS: We propose that the disruption of CMA-induced Plin5 degradation obstacles LD breakdown, explaining the lipid homeostasis imbalance in NAFLD.


Assuntos
Autofagia Mediada por Chaperonas , Hepatopatia Gordurosa não Alcoólica , Animais , Homeostase , Humanos , Metabolismo dos Lipídeos , Lipídeos , Fígado/metabolismo , Camundongos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Perilipina-5/metabolismo
7.
Zhonghua Fu Chan Ke Za Zhi ; 54(6): 375-380, 2019 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-31262121

RESUMO

Objective: To investigate the relationship between the previous cesarean scar thickness, previous cesarean scar defect and the occurrence of uterine rupture for pregnancy women after previous cesarean section and to predict the occurrence of uterine rupture in the third trimester for pregnancy women after previous cesarean section by analyzing the lower uterine segment (LUS) situation or quantitatively measure LUS myometrium thickness. Methods: A total of 154 pregnant women who have a prior cesarean from January 2015 to March 2016 were selected, all of them regularly did the prenatal examination in the pregnancy period and finally gave birth in hospital. By the transvaginal sonograph, the LUS myometrium thickness (transverse and longitudinal thickness) and the size of the previous cesarean scar defect were measured in the first trimester, the LUS myometrium thickness (longitudinal thickness) and qualitatively analysis LUS condition were measured in the third trimester. They were divided into two groups according to the pregnancy outcome: uterine rupture group (found in the cesarean operation or during the pregnancy) and without uterine rupture group (including the vaginal delivery women and those without uterine rupture in the cesarean operation period). The sensitivity and specificity of LUS myometrium thickness in the first trimester and the qualitative analysis LUS situation, the quantitative measurement of LUS myometrium thickness in the third trimester were compared in the prediction of occurrence of uterine rupture (dehiscence or complete rupture). Results: The group without uterine rupture included 134 women (6 vaginal delivery and 128 cesarean delivery), and the group with uterine rupture included 20 women (all of them cesarean delivery). The LUS myometrium thickness in the third trimester in the group without uterine rupture was (1.6±0.5) mm, and was (1.1±0.7) mm in the uterine rupture group (P= 0.004). There were no significant difference between two groups in the mean value of age, height, weight, the interdelivery interval, the LUS myometrium thickness (transverse and longitudinal thickness) in the first trimester. Qualitative analysis of LUS condition had higher specificity (99%), higher positive predictive value (92%), higher negative predictive value (94%) and slightly lower sensitivity (60%) than quantitative measure of LUS myometrium thickness in predicting uterine rupture. Conclusions: Measurement of the LUS myometrium thickness in the first trimester is helpful for predicting the occurrence of uterine rupture, so it is not necessary to terminate the pregnancy because of the thin LUS or the little prior cesarean scar defect in the first trimester. However it should be paid close attention to the LUS situation during the whole gestation. Qualitatively analyzing LUS situation is more meaningful than quantitatively measuring LUS myometrium thickness in predicting the uterine rupture in the third trimester.


Assuntos
Cicatriz , Miométrio/diagnóstico por imagem , Ruptura Uterina/prevenção & controle , Útero/diagnóstico por imagem , Cesárea , Feminino , Humanos , Gravidez , Ultrassonografia Pré-Natal , Ruptura Uterina/epidemiologia , Nascimento Vaginal Após Cesárea
8.
Vaccine ; 36(50): 7632-7640, 2018 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-30392766

RESUMO

The CD8+ T-cell response is an essential part of the adaptive immunity. Adjuvants are routinely required for priming of T cells against antigens encountered in lymph nodes (LNs) to generate antigen-specific immunity but may concomitantly trigger unexpected inflammatory responses. Sphingosine-1-phosphate (S1P) induces transient desensitization of S1P receptors on LN T cells and temporarily blocks their egress, leading to prolonged intranodal retention that allows effective immunosurveillance and increases the chance of priming. In light of the regulatory role of S1P in T-cell migration, we here develop a strategic approach to the T-cell priming with protein vaccine containing low-dose TLR-based adjuvants (LDAV) to induce antigen-specific CD8+ T cell responses as efficiently as using regular dose adjuvants in vaccine (RDAV). We found that when combined with one low dose of the S1P analog fingolimod administered into the same vaccination site posteriorly at a specific time, LDAV can elicit a primary response that reaches the level of that induced by RDAV with respect to the response magnitude and functionality. Time-course studies indicate that LDAV and fingolimod in combination act to mimic the expansion kinetics of RDAV-primed antigen-specific CD8+ T cells. Further, intranodal accumulation of cDC1 is markedly enhanced in mice receiving the combination vaccination despite the decrease in adjuvant use. Of particular note is the marginal cutaneous inflammation at the injection site, indicating an added benefit of using fingolimod. Therefore, fingolimod as a nonadjuvant agent essentially facilitates antigen-specific T-cell priming with reduced need of adjuvants and minimized adverse reactions.


Assuntos
Cloridrato de Fingolimode/metabolismo , Fatores Imunológicos/metabolismo , Ovalbumina/imunologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Animais , Anticorpos/sangue , Citocinas/análise , Ensaio de Imunoadsorção Enzimática , Cloridrato de Fingolimode/administração & dosagem , Fatores Imunológicos/administração & dosagem , Injeções Subcutâneas , Camundongos Endogâmicos C57BL , Ovalbumina/administração & dosagem , Vacinas de Subunidades/administração & dosagem , Vacinas de Subunidades/imunologia
9.
Benef Microbes ; 9(3): 401-416, 2018 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-29380642

RESUMO

This study examined the effects on intestinal microbiota and diarrhoea of Lactobacillus buchneri supplementation to the diet of weaning Rex rabbits. To this end, rabbits were treated with L. buchneri at two different doses (LC: 104 cfu/g diet and HC: 105 cfu/g diet) for 4 weeks. PCR-DGGE was used to determine the diversity of the intestinal microbiota, while real-time PCR permitted the detection of individual bacterial species. ELISA and real-time PCR allowed the identification of numerous cytokines in the intestinal tissues. Zonula occludens-1, polymeric immunoglobulin receptor and immunoglobulin A genes were examined to evaluate intestinal barriers. Results showed that the biodiversity of the intestinal microbiota of weaning Rex rabbits improved in the whole tract of the treated groups. The abundance of most detected bacterial species was highly increased in the duodenum, jejunum and ileum after L. buchneri administration. The species abundance in the HC group was more increased than in the LC group when compared to the control. Although the abundance of Enterobacteriaceae exhibited a different pattern, Escherichia coli was inhibited in all treatment groups. Toll-like receptor (TLR)2 and TLR4 genes were down-regulated in all intestinal tissues as the microbiota changed. In the LC group, the secretion of the inflammatory cytokine tumour necrosis factor-α was reduced, the gene expression of the anti-inflammatory cytokine interleukin (IL)-4 was up-regulated and the expression of intestinal-barrier-related genes was enhanced. Conversely, IL-4 expression was increased and the expression of other tested genes did not change in the HC group. The beneficial effects of LC were greater than those of HC or the control in terms of improving the daily weight gain and survival rate of weaning Rex rabbits and reducing their diarrhoea rate. Therefore, 104 cfu/g L. buchneri treatment improved the microbiota of weaning Rex rabbits and prevented diarrhoea in these animals.


Assuntos
Diarreia/veterinária , Microbioma Gastrointestinal , Lactobacillus/crescimento & desenvolvimento , Probióticos/administração & dosagem , Desmame , Animais , Citocinas/análise , Eletroforese em Gel de Gradiente Desnaturante , Diarreia/patologia , Diarreia/prevenção & controle , Ensaio de Imunoadsorção Enzimática , Intestinos/patologia , Reação em Cadeia da Polimerase , Coelhos , Resultado do Tratamento
10.
J Anim Physiol Anim Nutr (Berl) ; 102(1): e449-e459, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28771826

RESUMO

Probiotics promote the health of the host by maintaining intestinal microbial homeostasis. This study aimed to investigate the benefits of Lactobacillus plantarum BS22 (LP) in the gastrointestinal tract (GIT) microbial homeostasis of broiler chickens exposed to aflatoxin B1 using the PCR-DGGE, viable count and real-time PCR. The toxin adsorption experiment demonstrated that treatment R5 (1.0 × 108 CFU/g LP) exhibited good absorptive effect in adsorbing the aflatoxin B1 (AFB1 ) in vitro. DGGE showed that the composition and structure of gut microbiota were more similar in the mucosa than in the content of all the samples. In addition, higher diversity of the microbiota was observed in the caecum and glandular stomach than in other segments. Lactobacillus, Enterococcus and Enterobacteriaceae were more abundant in the ileum than in the other segments. Enterobacteriaceae in groups I (basal diet) and II (basal diet+50 µg/kg AFB1 ) showed a significant difference in group III (basal diet + 50 µg/kg AFB1  + 1 × 108 CFU/g LP) in the crop content and duodenum mucosa (p < .05). This investigation indicates that the L. plantarum BS22 promotes GIT microbial homeostasis in broiler chickens exposed to AFB1 , particularly for the intestine mucosa microbiota. Thus, L. plantarum BS22 is a possible candidate for degrading AFB1.


Assuntos
Aflatoxina B1/toxicidade , Bactérias/efeitos dos fármacos , Galinhas/microbiologia , Trato Gastrointestinal/microbiologia , Homeostase/efeitos dos fármacos , Lactobacillus plantarum/fisiologia , Animais , Bactérias/classificação , Bactérias/genética , DNA Bacteriano/genética , Microbioma Gastrointestinal/efeitos dos fármacos , Reação em Cadeia da Polimerase em Tempo Real
11.
Eur Rev Med Pharmacol Sci ; 21(22): 5096-5100, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29228448

RESUMO

OBJECTIVE: The aim of the present work was to study the prevention of liver cancer angiogenesis via miR-126. For this purpose, experimentations were conducted. MATERIALS AND METHODS: The precursor sequence of miR-126 was amplified in the DNA of human liver cancer cell lines. We, therefore, constructed the overexpression and interference vectors of miR-126 in vitro; which were respectively transferred to liver cancer cells in the logarithmic phase and inoculated under both sides of the back skin of Balb/c-nu nude mice aged 4-6 weeks with 10 mu l (1 x 105) cell suspension. The experiment consisted of non-vector control group, miR-126 overexpression group, and miR-126 inhibition group. Eight weeks later, the mice were sacrified; the tumor volumes and serum ALT, AFP, VEGF levels were compared. VEGF expression, as well as the microvascular density of the liver tissues, was detected via immunohistochemistry. RESULTS: Tumors volumes, serum ALT, AFP and VEGF levels and positive rates of VEGF were low in the miR-126 overexpression group and high in the miR-126 inhibition group, the difference being statistically significant (p < 0.05). CONCLUSIONS: At the end of this study, we conclude that miR-126 inhibits liver cancer angiogenesis.


Assuntos
Neoplasias Hepáticas/patologia , MicroRNAs/metabolismo , Alanina Transaminase/sangue , Animais , Antagomirs/metabolismo , Células Hep G2 , Humanos , Imuno-Histoquímica , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/metabolismo , Masculino , Camundongos , Camundongos Nus , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Neovascularização Patológica/prevenção & controle , Transplante Heterólogo , Carga Tumoral , Fator A de Crescimento do Endotélio Vascular/sangue , alfa-Fetoproteínas/análise
12.
J Dent Res ; 96(13): 1535-1545, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28759313

RESUMO

The mandibular condylar cartilage (MCC) shoulders force for the subchondral bone during mastication. The cartilage matrix contains various large molecules, such as type I, II, and X collagens and proteoglycans (PGs), which jointly play essential roles in maintaining cartilage characteristics. PGs play key roles in maintaining the elasticity of cartilage and providing a cushion against mastication forces. In addition to the well-known PGs, DMP1-PG, which is the PG form of dentin matrix protein 1 (DMP1), is a newly identified PG. DMP1 is proteolytically processed in vivo, and the N-terminus is glycosylated into its PG form-that is, DMP1-PG, which is highly expressed not only in tooth and bone but also in the matrix of the MCC. However, the specific functions of DMP1-PG in the MCC remain unclear. In human temporomandibular joint osteoarthritis and hyperocclusion model rat specimens, PGs are significantly downregulated, and DMP1-PG is the most prominently affected PG. To further investigate the role of DMP1-PG in condylar chondrogenesis, a glycosylation site mutant (S89-G89) mouse model was established with knock-in methods. In the MCC of the S89G-DMP1 mice, the glycosylation level of DMP1 was significantly downregulated, and a series of abnormal developmental and pathologic changes could be observed. The morphologic changes included thinner cartilage layers, deformations of the MCC, and disordered arrangements of the chondrocytes, and an earlier onset of temporomandibular joint osteoarthritis-like changes was observed. In addition, markers of chondrogenesis were downregulated, and the matrix of the MCC displayed OA phenotypes in the S89G-DMP1 mice. Further investigations showed that the transforming growth factor ß signaling molecules were affected in the MCC after the loss of DMP1-PG. In addition, the loss of DMP1-PG significantly accelerated the progression of cartilage injuries in the hyperocclusion models. Given these findings, we investigated the significant role of DMP1-PG in the chondrogenesis and maintenance of MCC.


Assuntos
Cartilagem/metabolismo , Condrogênese/efeitos dos fármacos , Proteínas da Matriz Extracelular/metabolismo , Glicosilação/efeitos dos fármacos , Côndilo Mandibular/metabolismo , Animais , Western Blotting , Modelos Animais de Doenças , Feminino , Humanos , Camundongos , Microscopia Eletrônica de Varredura , Osteoblastos/metabolismo , Proteoglicanas/metabolismo , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Microtomografia por Raio-X
13.
Klin Monbl Augenheilkd ; 232(5): 652-7, 2015 May.
Artigo em Alemão | MEDLINE | ID: mdl-25989034

RESUMO

Ocular graft-vs-host disease (GvHD) is a major complication following allogenic blood stem cell transplantation (aBSCT) leading to a disturbance of the ocular surface integrity with a broad range of severity. Leading symptom is a pronounced autoinflammatory reaction in particular at the ocular surface with typical features of dry eye disease. Potential complications include visual loss, pain and damage to the ocular structures with, e. g. corneal ulcerations. Diagnosis and treatment of ocular GvHD are a challenge for attending ophthalmologists and require intensive interdisciplinary patient care in particular with haemato-oncologists. First and follow-up examinations consist of several diagnostic steps that include quantitative and qualitative analysis of tearfilm, visual acuity, ocular surface and retinal integrity, cataract development and subjective symptoms. Available tests are mostly evaluated for usage in dry eye diagnosis but are, however, mostly unspecific for diagnosing ocular GvHD reliably. Only combinations of several clinical tests together with the experience of specialised ophthalmologists may lead to the certain diagnosis and treatment decisions at state. This review illustrates the available established and innovative non-invasive diagnostic tests and evaluates their potential use for diagnosing ocular GvHD.


Assuntos
Oftalmopatias/diagnóstico , Doença Enxerto-Hospedeiro/diagnóstico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doenças da Túnica Conjuntiva/diagnóstico , Doenças da Túnica Conjuntiva/etiologia , Doenças da Túnica Conjuntiva/terapia , Úlcera da Córnea/diagnóstico , Úlcera da Córnea/etiologia , Úlcera da Córnea/terapia , Técnicas de Diagnóstico Oftalmológico , Síndromes do Olho Seco/diagnóstico , Síndromes do Olho Seco/etiologia , Síndromes do Olho Seco/terapia , Oftalmopatias/etiologia , Oftalmopatias/terapia , Doença Enxerto-Hospedeiro/terapia , Humanos , Inquéritos e Questionários , Transtornos da Visão/diagnóstico , Transtornos da Visão/etiologia , Transtornos da Visão/terapia
14.
Neuroscience ; 262: 190-9, 2014 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-24406440

RESUMO

OBJECTIVE: Women are more prone to major depressive disorders (MDDs) and the incidence of MDD in women is almost twice that of men. Insular cortex abnormalities are a common finding in neuroanatomical studies of patients with MDD. However, it remains largely unclear whether female MDD patients at different clinical stages show morphologic changes in a specific subregion of the insular cortex. Additionally, it is not understood if any subregion changes can be used as a state or trait marker of MDD, and whether the diagnostic performance of any marker is sufficient to identify MDD. METHODS: Nineteen right-handed current MDD (cMDD) female patients and 19 remitted MDD (rMDD) patients, as well as 19 healthy controls matched for age and educational level, were recruited into the study. By means of voxel-based morphometry (VBM), we investigated gray matter volume abnormalities in insular subregions among the three groups and further conducted region-of-interest (ROI)-based receiver operating characteristic (ROC) analyses. The data from these investigations were correlated with clinical data to confirm the effectiveness of the identified changes in the subregions in differentiating the three groups. RESULTS: Both the cMDD and rMDD groups showed significantly decreased gray matter volumes in the left dorsal anterior insula compared to the healthy controls. The cMDD groups also showed decreased gray matter volumes in the right dorsal anterior insula relative to healthy controls. Further ROC comparisons demonstrated that the left dorsal anterior insula can effectively differentiate cMDD and rMDD groups from healthy controls. CONCLUSIONS: Our findings suggest that the volume changes in the left dorsal anterior insular cortex may be a trait-related marker of vulnerability to MDD and that the right dorsal anterior insular cortex may involve pathological changes of MDD.


Assuntos
Córtex Cerebral/patologia , Transtorno Depressivo Maior/patologia , Adolescente , Adulto , Idoso , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/tratamento farmacológico , Feminino , Lateralidade Funcional , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Fibras Nervosas Amielínicas/patologia , Tamanho do Órgão , Curva ROC , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Adulto Jovem
15.
Biocell ; 34(2): 91-4, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20925198

RESUMO

CXCL-12 and its receptor CXCR4 participate in breast cancer and melanoma cell metastasis to bone and lymphoid nodes. CD44, as a receptor for hyaluronic acid, is involved in lymphocyte recirculation, homing, adhesion and migration. But the role of CD44 in CXCL-12 induced leukemia cell migration still remains unclear. The present study showed that CXCL-12 stimulation induced the rapid internalization of CXCR4 and facilitated the formation of lamellipodia and uropod in acute leukemia cell line HL-60. CXCL-12 also induced CD44 translocation into the uropod, while CD44 remained evenly distributed on the untreated cell membranes. Results suggest that CD44 participates in CXCL-12 induced cell polarization and subsequent cell migration.


Assuntos
Polaridade Celular , Quimiocina CXCL12/imunologia , Receptores de Hialuronatos/imunologia , Leucemia Mieloide Aguda/imunologia , Animais , Movimento Celular/fisiologia , Extensões da Superfície Celular/metabolismo , Células HL-60 , Humanos , Receptores CXCR4
16.
Clin Imaging ; 25(2): 95-100, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11483417

RESUMO

This paper evaluated the accuracy of electron beam tomographic angiography (EBA) with conventional coronary arteriography (CCA) using four graded artificial stenoses in a postmortem swine coronary phantom model. The sensitivity, specificity, and accuracy of EBA for diagnosing significant stenosis (> or =50% stenosis) were 94.3%, 96.7%, and 95.8%, respectively. The diagnostic accuracy of EBA had no significant difference with CCA (chi(2)=0.0162; P>.05). EBA three-dimensional (3D) procedures had high interobserver reproducibility (k=.92-.95, P>.05). Maximum intensity projection (MIP) was the most sensitive and curved planar reformation (CPR) was the most accurate 3D procedure for quantitatively identifying coronary stenosis. EBA yields promising results concerning the visualization of coronary artery stenosis with high accuracy for stenoses >50%.


Assuntos
Doença das Coronárias/diagnóstico por imagem , Intensificação de Imagem Radiográfica/métodos , Tomografia Computadorizada por Raios X/métodos , Animais , Meios de Contraste , Angiografia Coronária/métodos , Modelos Animais de Doenças , Imageamento Tridimensional , Imagens de Fantasmas , Sensibilidade e Especificidade , Suínos
17.
Acad Radiol ; 8(8): 726-33, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11508751

RESUMO

RATIONALE AND OBJECTIVES: The authors performed this study to evaluate a new method (medial axis reformation [MAR]) for visualizing three-dimensional vascular data at electron-beam computed tomographic (CT) angiography. MATERIALS AND METHODS: MAR was performed automatically with a personal computer-based workstation. After the region of interest was edited, voxels were divided into groups according to their path lengths. Centroids of groups were connected to form the medial axis. Then, the medial axis was refined with multiscale medial response. Bifurcations were also detected and refined. Finally, curved sections were generated through the branches and laid out onto a single image by using a splitting method. The authors performed MAR during electron-beam CT angiography of coronary arteries, common carotid arteries, and iliac arteries. RESULTS: MAR displayed curved sections of branched vessels on one image, cut through the axis of vessels to show the vessel diameter objectively, and allowed the viewing direction to be altered arbitrarily. CONCLUSION: Results of preliminary applications demonstrate that MAR is a valuable new visualization method for CT angiography.


Assuntos
Angiografia/métodos , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/métodos , Adulto , Algoritmos , Animais , Artérias Carótidas/diagnóstico por imagem , Doença das Coronárias/diagnóstico por imagem , Vasos Coronários/patologia , Feminino , Humanos , Imageamento Tridimensional/métodos , Masculino , Microcomputadores , Pessoa de Meia-Idade , Suínos
18.
Chin Med J (Engl) ; 114(5): 466-72, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11780405

RESUMO

OBJECTIVE: To establish and evaluate two protocols for the noninvasive visualization and assessment of coronary artery bypass graft (CABG) patency on electron beam tomography (EBT). METHODS: Two hundred and fourteen consecutive patients who underwent coronary artery bypass graft surgery were scanned using both EBT angiography with 3-dimensional reconstruction and EBT flow study with time-density-curve analysis. RESULTS: There were 589 CABGs evaluated in this study (10 grafts were excluded because of artifacts). Among them, 133 (98.5%) of 135 arterial grafts were patent, and 345 (77.7%) of 444 saphenous-vein grafts were patent. Within 5 years or between 5 and 10 years after operation, arterial graft patency exceeded venous graft patency (P < 0.001). Three-dimensional EBT angiography achieved higher sensitivity, specificity and accuracy (97.7%, 94.1% and 96.7%, respectively) than did EBT flow study (88.4%, 82.4% and 85.2%, respectively) for evaluating occlusion or patency of CABG. The intra-graft flow of patent arterial and venous grafts were 4.9 +/- 2.2 ml.min-1.g-1 and 6.9 +/- 2.8 ml.min-1.g-1, respectively (P < 0.001). CONCLUSION: The combination of EBT three-dimensional reconstruction and flow study can be more effective in the assessment of CABG anatomy and quantification of patent CABG blood flow.


Assuntos
Ponte de Artéria Coronária , Circulação Coronária , Processamento de Imagem Assistida por Computador , Tomografia Computadorizada por Raios X , Adulto , Idoso , Idoso de 80 Anos ou mais , Angiografia Coronária , Feminino , Humanos , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade
19.
Angiology ; 51(11): 895-904, 2000 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11103858

RESUMO

In this study, the authors evaluated the performance characteristics of contrast-enhanced electron-beam tomography (EBT) with three-dimensional reconstruction in defining the coronary artery lumen in healthy subjects. Thirty patients with normal coronary angiograms by selective coronary arteriography (SCA) underwent contrast-enhanced EBT examination. Measured parameters included degree of luminal enhancement, intravascular contrast-to-noise ratio (CNR), and diameter and length of visualized lumen. Ventricular cavity, aortic blood pool, and coronary artery attenuation were found to be significantly different before and after intravenous injection of contrast material (p < 0.001). CNR decreased from proximal to distal segments within each vessel (p < 0.001), with a peak of 11.2 +/- 2.3 occurring in the proximal left anterior descending coronary artery (LAD) to a low of 4.8 +/- 2.0 in the distal left circumflex (LCX). Luminal diameters visualized by EBT had no significant difference with that of SCA (p > 0.05). Therefore, EBT angiography with three-dimensional reconstruction allows for noninvasive coronary arteriography revealing long segments of the major coronary arteries in normal subjects.


Assuntos
Angiografia Coronária , Processamento de Imagem Assistida por Computador , Tomografia Computadorizada por Raios X , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
20.
J Comput Assist Tomogr ; 24(5): 663-70, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-11045683

RESUMO

OBJECTIVES: To establish and evaluate two protocols for the noninvasive visualization and assessment of coronary artery bypass graft (CABG) patency on electron beam tomography (EBT). METHODS: Two hundred fourteen consecutive patients who underwent CABG surgery were scanned using both EBT angiography with three-dimensional reconstruction and EBT flow study with time-density curve analysis. RESULTS: There was a total of 589 CABGs evaluated in this study (10 grafts were excluded because of artifacts); 133 (98.5%) of 135 arterial grafts were patent, 345 (77.7%) of 444 saphenous vein grafts were patent. Within 5 years or 5-10 years after surgery, arterial graft patency exceeded venous graft patency (p<0.001). Three-dimensional EBT angiography achieved higher sensitivity, specificity, and accuracy (97.7%, 94.1%, and 96.7%, respectively) than EBT flow study (88.4%, 82.4%, and 85.2%, respectively) for evaluating occlusion or patency of CABGs. The intragraft flow of patent arterial and venous grafts were 4.9+/-2.2 ml/min/g and 6.9+/-2.8 ml/min/g, respectively (p<0.001). CONCLUSION: The combination of EBT three-dimensional reconstruction and flow study can be more effectively performed in the assessment of CABG anatomy and quantification of patent CABG flow.


Assuntos
Ponte de Artéria Coronária , Oclusão de Enxerto Vascular/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Angiografia Coronária , Circulação Coronária , Feminino , Seguimentos , Humanos , Processamento de Imagem Assistida por Computador/métodos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Fatores de Tempo , Grau de Desobstrução Vascular
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