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In this study, we optimized the parameters of diffusion bonding on multi-layered stainless steel 316L and 430 stacks. The preparation process for diffusion bonding is crucial, as the bonding surfaces need to be polished and meticulously cleaned to ensure a smooth bonding process. We fabricated twelve-layer plates consisting of 55 mm × 55 mm × 3 mm and 100 mm × 50 mm × 3 mm dimensions, and the bonding response was investigated by evaluating the tensile strength of the bonding zone under varying bonding conditions, with a bonding temperature ranging from 1000 to 1048 °C, a bond time ranging from 15 to 60 min, pressure ranging from 10 to 25.3 MPa, and under a vacuum environment. SS430 exhibits a significantly higher compression creep rate than SS316L. The compressibility of diffusion welding materials does not impact the diffusion bonding strength. Multi-axial tensile strength tests confirmed strong bonding joint strength in various axes. The tensile strengths of monolithic and Diffusion bonding (DB) specimens tested in parallel are essentially identical. The optimized diffusion bonding parameters (Condition G2C: 1048 °C/25.3 MPa/15 min) are ideal for producing SS316L stainless steel cores in compact heat exchangers, offering a superior bonding quality and reduced costs. These findings have practical implications for the production of stainless steel cores in compact heat exchangers, demonstrating the relevance and applicability of our research.
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Cistite , Imageamento por Ressonância Magnética Multiparamétrica , Neoplasias da Bexiga Urinária , Masculino , Humanos , Bexiga Urinária/diagnóstico por imagem , Próstata/diagnóstico por imagem , Cistite/complicações , Cistite/diagnóstico por imagem , Hemorragia/diagnóstico por imagem , Hemorragia/etiologia , Neoplasias da Bexiga Urinária/complicaçõesRESUMO
Objective: Tumor recurrence remains the main dilemma after surgical treatment of ampulla of Vater carcinoma. This study was designed to identify the prognostic factors and evaluate the recurrence patterns of ampulla of Vater cancer. Methods: A total of 286 patients who underwent surgical resection of ampulla of Vater cancer in two medical centers from January 2000 to October 2016 were collected. Data on clinicopathologic factors, survival rate, and recurrence patterns were retrospectively analyzed. Results: A total of 158 patients (55.2%) survived without evidence of recurrence (non-recurrence), whereas 65 (22.7%) and 63 patients (22.1%) suffered from recurrence of the disease within 12 months (early recurrence) and after 12 months (late recurrence), respectively. Early-recurrence patients exhibited a more advanced disease (advanced tumor stage, lymph node involvement, pancreas invasion, and late TNM stage) than late-recurrence patients. The first or primary location of cancer recurrence in 33 patients (25.8%) was locoregional. Metastasis developed in the liver in 30 patients (23.4%), peritoneum in 13 patients (10.2%), lungs in 10 patients (7.8%), and para-aortic or superior mesenteric artery lymph node in 10 patients (7.8%). Multiple metastases were observed in 26 patients (20.3%). Conclusion: The most common patterns of postoperative recurrence are locoregional and recurrent liver metastasis. The recurrence patterns with the worst prognosis are peritoneal and multiple metastases.
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Proteins in Jumonji family function as histone demethylases and participate in cardiac development. Jumonji domain containing 5 (JMJD5) is responsible for the embryonic development through removing methyl moieties from H3K36me2 histone, and has pro-proliferative effect on heart and eye development. However, the protective role of JMJD5 against oxygen-glucose deprivation and reperfusion (OGD/R)-induced injury in cardiomyocytes has not been fully understood. Firstly, myocardial ischemia/reperfusion (I/R) rat model was established by ligation of left coronary artery. OGD/R was performed in non-transfected H9C2 or H9C2 transfected with pcDNA-JMJD5 plasmid to induce cell cytotoxicity. Data from qRT-PCR and western blot showed that JMJD5 was reduced in the heart tissues of myocardial I/R rat model and OGD/R-induced H9C2. Secondly, JMJD5 over-expression attenuated OGD/R-induced decrease in cell viability and increase in lactate dehydrogenase secretion and cell apoptosis in H9C2. Mitophagy was promoted by pcDNA-mediated over-expression of JMJD5 with enhanced protein expression of LC3-I, LC3-II, Atg5, and Beclin 1. Thirdly, knockdown of JMJD5 aggravated OGD/R-induced decrease in hypoxia-inducible factor-1α (HIF-1α), whereas JMJD5 over-expression enhanced BNIP3 (Bcl-2/adenovirus E1B 19-kDa interacting protein) through upregulation of HIF-1α. Lastly, BNIP3 silencing promoted cell apoptosis, suppressed mitophagy, and attenuated the protective effects of JMJD5 over-expression against OGD/R-induced injury in H9C2. In conclusion, JMJD5 exerted protective effects against OGD/R-induced injury in cardiomyocytes through upregulation of HIF-1α-BNIP3.
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Glucose , Traumatismo por Reperfusão Miocárdica/metabolismo , Miócitos Cardíacos/metabolismo , Oxigênio/metabolismo , Animais , Apoptose , Sobrevivência Celular , Modelos Animais de Doenças , Glucose/deficiência , Glucose/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Histona Desmetilases com o Domínio Jumonji , Proteínas de Membrana/metabolismo , Proteínas Mitocondriais/metabolismo , Mitofagia , Traumatismo por Reperfusão Miocárdica/induzido quimicamente , Traumatismo por Reperfusão Miocárdica/enzimologia , Miócitos Cardíacos/citologia , Substâncias Protetoras , RatosRESUMO
BACKGROUND: Juvenile idiopathic arthritis (JIA) is a chronic inflammatory disease that includes seven heterogeneous subgroups with different prognoses. In particular, polyarticular JIA (pJIA) has a longer period of active disease and a poorer prognosis. Tumor necrosis factor (TNF)-alpha inhibitors are effective in patients with pJIA, but the therapeutic regimen remains controversial. Here, we performed a single-center study to determine the potential correlation between TNF-alpha inhibitor (infliximab) therapy and outcomes in these patients. METHODS: Clinical data of 40 pJIA patients were collected at our center from January 1, 2010 to January 1, 2018, and patients were grouped according to the timing of infliximab therapy. The erythrocyte sedimentation rate (ESR), the number of joints with active disease, and the 27-point juvenile arthritis disease activity score (JADAS-27) were analyzed. RESULTS: The ESR, the active joint count, and the JADAS-27 decreased significantly in all groups after 3 months (P = 0.041/0.415/0.008, 0.022/0.030/ < 0.001, and 0.05/0.012/ < 0.001, respectively) and 6 months (P = 0.036/0.045/0.041, 0.076/0.037/ < 0.001, and 0.096/0.006/ < 0.001, respectively) of infliximab treatment, although the rates of change of these parameters were similar. However, after 12 months, only patients treated with infliximab within 3 months of disease onset had a stable ESR, active joint count, and JADAS-27, while these parameters increased sharply when infliximab was administered 3 months and especially 1 year after disease onset. CONCLUSIONS: TNF-alpha is a pleiotropic pro-inflammatory cytokine of crucial importance in the pathogenesis of JIA. Infliximab can improve the outcomes of patients with pJIA significantly, and should be introduced early during the clinical course.
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Antirreumáticos/uso terapêutico , Artrite Juvenil/tratamento farmacológico , Infliximab/uso terapêutico , Adolescente , Criança , Pré-Escolar , China , Feminino , Humanos , Lactente , Masculino , Estudos RetrospectivosRESUMO
BACKGROUND: It has recently been recognized that serum vimentin is elevated in infectious diseases, and that vimentin plays a role in regulating neutrophils and macrophages associated inflammation. However, the mechanisms are unclear. This study was designed to explore the role of vimentin in regulating monocyte survival or apoptosis as well as inflammatory cytokine secretion in response to lipopolysaccharides (LPSs). METHODS: A human monocytic leukemia cell line (THP-1) was transfected with vimentin-specific small interfering RNA (siRNA) or vimentin over-expressing plasmid. Apoptosis was assessed by TdT-mediated dUTP Nick-End Labeling (TUNEL) and DNA content assay. Immunoblotting was performed to detect apoptosis-associated proteins. Cytokines (interleukin [IL]-6, IL-10, and tumor necrosis factor α [TNF-α]) were measured by enzyme-linked immuno sorbent assay. Two-way analysis of variance followed by Student's t test was used to compare means between different groups. RESULTS: Suppression of vimentin in THP-1 cells resulted in increased apoptotic response in the presence of LPS, while over-expression of vimentin could prevent the cells from apoptosis in response to LPS. LPS alone or suppression of vimentin resulted in significant up-regulation of caspase-3 (1.42â±â0.20 of LPS alone and 1.68â±â0.10 of vimentin suppression vs. control, tâ=â5.21 and 10.28, respectively, Pâ<â0.05). In addition, pro-inflammatory cytokines (IL-6 and TNF-α) was significantly increased (IL-6: 577.90â±â159.90 pg/day/10 cells vs. 283.80â±â124.60 pg/day/10 cells of control, tâ=â14.76, Pâ<â0.05; TNF-α: 54.10â±â5.80 vs. 17.10â±â0.10 pg/day/10 cells of control, tâ=â6.71, Pâ<â0.05), while anti-inflammatory cytokine (IL-10) was significantly up-regulated in the THP-1 cells that over-expressed vimentin (140.9â±â17.2 pg/day/10 cells vs. undetectable in control cells). CONCLUSIONS: In summary, the vimentin may regulate innate immunity through modulating monocytes viability as well as inflammatory response in sepsis through shifting the balance of pro-inflammatory and anti-inflammatory cytokines.
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Citocinas/metabolismo , Inflamação/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Vimentina/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Humanos , Immunoblotting , Marcação In Situ das Extremidades Cortadas , Interleucina-10/metabolismo , Macrófagos/metabolismo , RNA Interferente Pequeno/metabolismo , Fator de Necrose Tumoral alfa/metabolismoAssuntos
Doenças dos Nervos Cranianos/diagnóstico , Linfoma não Hodgkin/diagnóstico , Adulto , Idoso , Doenças dos Nervos Cranianos/líquido cefalorraquidiano , Doenças dos Nervos Cranianos/complicações , Doenças dos Nervos Cranianos/patologia , Diagnóstico Diferencial , Feminino , Humanos , Linfoma não Hodgkin/líquido cefalorraquidiano , Linfoma não Hodgkin/complicações , Linfoma não Hodgkin/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
INTRODUCTION: Few studies have applied diffusion kurtosis imaging (DKI) and diffusion tensor imaging (DTI) for the comprehensive assessment of gliomas [tumour grade, isocitrate dehydrogenase-1 (IDH-1) mutation status and tumour proliferation rate (Ki-67)]. This study describes the efficacy of DKI and DTI to comprehensively evaluate gliomas, compares their results. METHODS: Fifty-two patients (18 females; median age, 47.5 years) with pathologically proved gliomas were prospectively included. All cases underwent DKI examination. DKI (mean kurtosis: MK, axial kurtosis: Ka, radial kurtosis: Kr) and DTI (mean diffusivity: MD, fractional anisotropy: FA) maps of each metric was derived. Three ROIs were manually drawn. RESULTS: MK, Ka, Kr and FA were significantly higher in HGGs than in LGGs, whereas MD was significantly lower in HGGs than in LGGs (P < 0.01). ROC analysis demonstrated that MK (specificity: 100% sensitivity: 79%) and Ka (specificity: 96% sensitivity: 82%) had the same and highest (AUC: 0.93) diagnostic value. Moreover, MK, Ka, and Kr were significantly higher in grade III than II gliomas (P ⦠0.01). Further, DKI and DTI can significantly identify IDH-1 mutation status (P ⦠0.03). Ka (sensitivity: 74%, specificity: 75%, AUC: 0.72) showed the highest diagnostic value. In addition, DKI metrics and MD showed significant correlations with Ki-67 (P ⦠0.01) and Ka had the highest correlation coefficient (rs = 0.72). CONCLUSIONS: Compared with DTI, DKI has great advantages for the comprehensive assessment of gliomas. Ka might serve as a promising imaging index in predicting glioma grading, tumour cell proliferation rate and IDH-1 gene mutation status.
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Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Imagem de Difusão por Ressonância Magnética , Imagem de Tensor de Difusão , Glioma/diagnóstico por imagem , Glioma/patologia , Isocitrato Desidrogenase/genética , Adulto , Idoso , Neoplasias Encefálicas/genética , Proliferação de Células , Feminino , Glioma/genética , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Gradação de Tumores , Estudos Prospectivos , Sensibilidade e Especificidade , Adulto JovemRESUMO
Background and purpose: Neurite orientation dispersion and density imaging (NODDI) is a new diffusion MRI technique that has rarely been applied for glioma grading. The purpose of this study was to quantitatively evaluate the diagnostic efficiency of NODDI in tumour parenchyma (TP) and peritumoural area (PT) for grading gliomas and detecting isocitrate dehydrogenase-1 (IDH-1) mutation status. Methods: Forty-two patients (male: 23, female: 19, mean age: 44.5 y) were recruited and underwent whole brain NODDI examination. Intracellular volume fraction (icvf) and orientation dispersion index (ODI) maps were derived. Three ROIs were manually placed on TP and PT regions for each case. The corresponding average values of icvf and ODI were calculated, and their diagnostic efficiency was assessed. Results: Tumours with high icvfTP (≥0.306) and low icvfPT (≤0.331) were more likely to be high-grade gliomas (HGGs), while lesions with low icvfTP (<0.306) and high icvfPT (>0.331) were prone to be low-grade gliomas (LGGs) (Pâ¯<â¯0.001). A multivariate logistic regression model including patient age and icvf values in TP and PT regions most accurately predicted glioma grade (AUCâ¯=â¯0.92, Pâ¯<â¯0.001), with a sensitivity and specificity of 92% and 89%, respectively. However, no significant differences were found in NODDI metrics for differentiating IDH-1 mutation status. Conclusions: The quantitative NODDI metrics in the TP and PT regions are highly valuable for glioma grading. A multivariate logistic regression model using the patient age and the icvf values in TP and PT regions showed very high predictive power. However, the utility of NODDI metrics for detecting IDH-1 mutation status has not been fully explored, as a larger sample size may be necessary to uncover benefits.
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Neoplasias Encefálicas/patologia , Encéfalo/patologia , Glioma/patologia , Isocitrato Desidrogenase/genética , Adulto , Idoso , Neoplasias Encefálicas/genética , Imagem de Difusão por Ressonância Magnética/métodos , Imagem de Tensor de Difusão/métodos , Feminino , Glioma/genética , Humanos , Masculino , Pessoa de Meia-Idade , Mutação/genética , Neuritos , Neuroimagem/métodos , Sensibilidade e EspecificidadeRESUMO
OBJECTIVES: Temporomandibular joint osteoarthritis (TMJOA) is approximately twice as prevalent in women than in men. Synoviocytes are believed to play a critical role in joint inflammation. However, it is unknown whether synoviocytes from different genders possess sexual dimorphisms that contribute to female-predominant TMJOA. MATERIALS AND METHODS: Freund's complete adjuvant combined with monosodium iodoacetate was used to induce TMJOA in female and male rats. Histologic and radiographic features were used to evaluate TMJOA. The expression of CD68, MCP-1, iNOS, and IL-1ß was detected by immunohistochemistry and real-time PCR. Primary fibroblast-like synoviocytes (FLSs) isolated from the synovial membrane of female and male rats were used for in vitro experiments. RESULTS: Female rats showed aggravated TMJOA features as compared to male rats. Increased expression of iNOS and IL-1ß was detected in synovial membrane from female TMJOA rats as compared to male rats. Furthermore, greater amounts of CD68-positive macrophage infiltration and increased MCP-1 expression around the synovial membrane were detected in female TMJOA rats compared to males. Primary cultured FLSs from female rats showed higher sensitivity to TNF-α treatment and recruited increased macrophage migration than male FLSs. More important, ovariectomy (OVX) by ablation in female rats repressed the sensitivity of female FLSs to TNF-α treatment due to the loss of estrogen production. Blockage of the estrogen receptor repressed estrogen-potentiated TNF-α-induced pro-inflammatory cytokine expression in OVX-FLSs. Moreover, the injection of estrogen receptor antagonists relieved the cartilage destruction and bone deterioration of TMJOA in female rats. CONCLUSION: Estrogen-sensitized synoviocytes in female rats may contribute to gender differences in the incidence and progression of TMJOA.
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Estrogênios , Osteoartrite/metabolismo , Sinoviócitos/metabolismo , Transtornos da Articulação Temporomandibular/metabolismo , Animais , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Quimiocina CCL2/metabolismo , Antagonistas do Receptor de Estrogênio/farmacologia , Estrogênios/metabolismo , Estrogênios/farmacologia , Feminino , Interleucina-1beta/metabolismo , Macrófagos/metabolismo , Macrófagos/fisiologia , Masculino , Óxido Nítrico Sintase Tipo II/metabolismo , Osteoartrite/patologia , Ovariectomia , Ratos , Ratos Sprague-Dawley , Receptores de Estrogênio/antagonistas & inibidores , Fatores Sexuais , Membrana Sinovial/metabolismo , Sinoviócitos/efeitos dos fármacos , Fator de Necrose Tumoral alfa/farmacologiaAssuntos
Gasometria , Hiperóxia , Aconitato Hidratase , Dióxido de Carbono , Humanos , Consumo de OxigênioRESUMO
Sclerosing angiomatoid nodular transformation (SANT) is a rare benign splenic vascular lesion. Since it was first defined in 2004, a total of 132 cases of SANT have been reported in ~50 studies in the English literature. However, it remains difficult to form a definitive pre-operative differential diagnosis of SANT compared with other splenic tumors or malignant lesions. The present study reports a pathologically proven case of SANT in a 29-year-old man who initially presented with left upper quadrant and back discomfort. The study also provides a review of the current knowledge on the condition, including the clinical profile, imaging features, cytological features, differential diagnosis and treatment of SANT. The most important distinguishing features of SANT are its typical vascular character and lack of other features that are typical of a granuloma. A splenectomy is required and the diagnosis is based on pathological analysis.
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In this paper, 3-aminobenzeneboronic acid functionalized Mn(2+)-doped ZnTe/ZnSe quantum dots (APBA-dQDs) were prepared. The APBA functional groups had strong binding ability with F(-), resulting in the quenchment of dQDs photoluminescence (PL). Under the optimal condition, the fluorescence intensity of APBA-dQDs was related linearly to the concentration of F(-) in the range of 0.25-1.5µmol/L with a detection limit of 0.1µmol/L. The selectivity of fluorescence quenching of APBA-dQDs for F(-) was enhanced. Moreover, the proposed methodology for the sensing of F(-) at EM 560nm in MC3T3-E1 osteoblastic cells was demonstrated and got a satisfactory results. The results indicate that the APBA-dQDs are promising candidates for intracellular in MC3T3-E1 osteoblastic cells. To the best of our knowledge, it was the first report of F(-) sensing by using the quenched fluorescence of APBA-dQDs in non-cancerous cells.
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Ácidos Borônicos/química , Fluoretos/análise , Manganês/química , Pontos Quânticos/química , Compostos de Selênio/química , Telúrio/química , Compostos de Zinco/química , Animais , Linhagem Celular , Fluoretos/química , Camundongos , OsteoblastosRESUMO
BACKGROUND: Wiskott-Aldrich syndrome (WAS) and X-linked thrombocytopenia (XLT) are caused by mutations of the WAS gene. The genotype-phenotype association of WAS and XLT have not been fully elucidated. Here, we established the largest database of WAS in China to further determine the potential correlation between genotype and phenotype and long-term outcome. PROCEDURES: We collected clinical data of 81 WAS/XLT patients, analyzed mutations of WAS gene at the genomic DNA and transcriptional/translational levels, and quantified three different patterns of WAS protein (WASp) expression in PBMCs by flow cytometry. RESULTS: There were 60 unique mutations identified, including 20 novel mutations and eight hotspots, from 75 unrelated families with a total of 81 affected members. Nearly all the patients with XLT had missense mutations and were WASp-positive in the peripheral cells, while only half of the patients with missense mutations exhibited the XLT phenotype and detectable WASp. In contrast, patients with nonsense mutations, deletions, insertions, and complex mutations were WASp-negative and developed the classic WAS phenotype. An equal number of patients with splice anomalies were either WASp-positive or WASp-negative. Long-term survival rates were lower in WASp-negative patients compared to WASp-positive patients. CONCLUSIONS: The clinical phenotype of classic WAS or milder XLT and long-term outcome are potentially influenced by the effect of these defects on gene transcription and translation. Patients with missense mutations allowing expression of mutated WASp and those with splice anomalies, which result in generation of multiple products, including normal WASp, present the attenuated XLT phenotype and show better prognosis.
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Doenças Genéticas Ligadas ao Cromossomo X/genética , Mutação , Trombocitopenia/genética , Proteína da Síndrome de Wiskott-Aldrich/genética , Síndrome de Wiskott-Aldrich/genética , Idade de Início , Pré-Escolar , China/epidemiologia , Análise Mutacional de DNA , Bases de Dados Genéticas , Doenças em Gêmeos/genética , Citometria de Fluxo , Regulação da Expressão Gênica , Doenças Genéticas Ligadas ao Cromossomo X/epidemiologia , Genótipo , Transplante de Células-Tronco Hematopoéticas , Humanos , Lactente , Recém-Nascido , Masculino , Fenótipo , Biossíntese de Proteínas , Taxa de Sobrevida , Trombocitopenia/epidemiologia , Transcrição Gênica , Resultado do Tratamento , Síndrome de Wiskott-Aldrich/epidemiologia , Síndrome de Wiskott-Aldrich/terapia , Proteína da Síndrome de Wiskott-Aldrich/biossíntese , Proteína da Síndrome de Wiskott-Aldrich/deficiênciaRESUMO
BACKGROUND: After cardiac surgery, central venous oxygen saturation (ScvO 2 ) and serum lactate concentration are often used to guide resuscitation; however, neither are completely reliable indicators of global tissue hypoxia. This observational study aimed to establish whether the ratio between the veno-arterial carbon dioxide and the arterial-venous oxygen differences (P(v-a)CO 2 /C(a-v)O 2 ) could predict whether patients would respond to resuscitation by increasing oxygen delivery (DO 2 ). METHODS: We selected 72 patients from a cohort of 290 who had undergone cardiac surgery in our institution between January 2012 and August 2014. The selected patients were managed postoperatively on the Intensive Care Unit, had a normal ScvO 2 , elevated serum lactate concentration, and responded to resuscitation by increasing DO 2 by >10%. As a consequence, 48 patients responded with an increase in oxygen consumption (VO 2 ) while VO 2 was static or fell in 24. RESULTS: At baseline and before resuscitative intervention in postoperative cardiac surgery patients, a P(v-a)CO 2 /C(a-v)O 2 ratio ≥1.6 mmHg/ml predicted a positive VO 2 response to an increase in DO 2 of >10% with a sensitivity of 68.8% and a specificity of 87.5%. CONCLUSIONS: P(v-a)CO 2 /C(a-v)O 2 ratio appears to be a reliable marker of global anaerobic metabolism and predicts response to DO 2 challenge. Thus, patients likely to benefit from resuscitation can be identified promptly, the P(v-a)CO 2 /C(a-v)O 2 ratio may, therefore, be a useful resuscitation target.
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Dióxido de Carbono/sangue , Hiperlactatemia/sangue , Adulto , Idoso , Gasometria , Procedimentos Cirúrgicos Cardíacos , Feminino , Humanos , Hiperlactatemia/terapia , Unidades de Terapia Intensiva/estatística & dados numéricos , Ácido Láctico/sangue , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio/fisiologia , Estudos Prospectivos , RessuscitaçãoRESUMO
UNLABELLED: Autoimmune disease (AD) is common in patients with Wiskott-Aldrich syndrome (WAS) and patients with WAS who has an AD usually constitute a high-risk group with poor outcome. However, knowledge of AD in WAS is limited in China. In this study, medical records of 53 patients with WAS at Children´s Hospital of Chongqing Medical University from April 2004 to January 2014 were evaluated retrospectively and 14 patients (26%) had at least one AD. Autoimmune hemolytic anemia (AIHA) was the most common and detected in 12 patients (23%), other complications included immune thrombocytopenia (n = 1), immune neutropenia (n = 1), autoimmune arthritis (n = 1), and renal injury (n = 1). No significant differences were found in the level of serum immunoglobulins and lymphocyte subsets between the AD group and non-AD group. Although eight patients with AD received hematopoietic stem cell transplantation (HSCT), three patients died of pulmonary infection after HSCT. CONCLUSIONS: AD is frequent in Chinese patients with WAS and AIHA was the most common. AD is a poor prognosis factor for WAS and should be treated as early as possible by HSCT. WHAT IS KNOWN: ⢠Autoimmune disease is common in patients with WAS. ⢠Manifestations, follow-up finding, and treatment approaches of autoimmune disease in Chinese patients with WAS have received less attention in the literature. What is New: ⢠This study is firstly intended for evaluation of the clinical and immune characteristics of autoimmune disease in a large series Chinese patients with WAS. ⢠AD is frequent in Chinese patients with WAS and AIHA is the most common.
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Autoimunidade , Transplante de Células-Tronco Hematopoéticas/métodos , Imunossupressores/uso terapêutico , Linfócitos T/imunologia , Síndrome de Wiskott-Aldrich/imunologia , Pré-Escolar , China/epidemiologia , Feminino , Citometria de Fluxo , Seguimentos , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Síndrome de Wiskott-Aldrich/epidemiologia , Síndrome de Wiskott-Aldrich/terapiaRESUMO
Parathyroid hormone (PTH), PTH-related peptide (PTHrP), and calcium-sensing receptor (CaSR) play important roles in maintaining calcium homeostasis. Here, we study the effect of fluoride on expression of PTH, PTHrP, and CaSR both in vitro and in vivo. MC3T3-E1 cells and Sprague-Dawley rats were treated with different concentrations of fluoride. Then, the free calcium ion concentration in cell culture supernatant and serum were measured by biochemical analyzer. The expression of PTH, PTHrP, and CaSR was analyzed by qRT-PCR and Western blot. We found that the low dose of fluoride increased ionized calcium (i[Ca(2+)]) and the high dose of fluoride decreased i[Ca(2+)] in cell culture supernatant. The low dose of fluoride inhibited the PTH and PTHrP expression in MC3T3-E1 cells. The high dose of fluoride improved the PTHrP expression in MC3T3-E1 cells. Interestingly, we found that NaF decreased serum i[Ca(2+)] in rats. Fluoride increased CaSR expression at both messenger RNA (mRNA) and protein levels in MC3T3-E1 cells and rats. The expression of PTHrP protein was inhibited by fluoride in rats fed regular diet and was increased by fluoride in rats fed low-calcium diet. Fluoride also increased the expression of PTH, NF-kappaB ligand (RANKL), and osteoprotegerin (OPG) in rats. The ratio of RANKL/OPG in rats fed low-calcium food in presence or absence of fluoride was significantly increased. These results indicated that fluoride might be able to affect calcium homeostasis by regulating PTH, PTHrP, and CaSR.
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Cálcio/química , Proteína Relacionada ao Hormônio Paratireóideo/metabolismo , Hormônio Paratireóideo/metabolismo , Receptores de Detecção de Cálcio/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Fluoreto de Sódio/química , Células 3T3 , Animais , Regulação da Expressão Gênica , Homeostase , Masculino , Camundongos , Osteoblastos/efeitos dos fármacos , Osteoprotegerina/metabolismo , Ligante RANK/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
AIMS: Phagocytosis plays essential roles during inflammation and immune response. This study aims to explore the underlying mechanism of corticotropin-releasing hormone (CRH) and urocortin (UCN)-promoted phagocytosis of rat macrophages. MAIN METHODS: To induce phagocytosis, rat macrophages were incubated with carboxylated fluorescent microspheres. The phagocytosis activity was evaluated by flow cytometric analysis. Actin reorganization was determined by immunostaining with TRITC-labeled phalloidin and transmission electron microscopy (TEM) analysis. Protein expressions of p-RhoA, p-Rac1, p-extracellular signal-related kinase (ERK)1/2 and GAPDH were examined by Western blotting. Protein kinase C (PKC) and protein kinase A (PKA) activities were examined using PreTag non-radio activity assay. KEY FINDINGS: Administration of CRH or UCN alone significantly enhanced phagocytosis of microspheres by rat macrophages, as well as actin reorganization. Ligation of CRH and UCN with CRH receptor increased the phosphorylation of both RhoA and Rac1. Inhibition of RhoA/Rac1 signal pathway suppressed CRH- or UCN-enhanced phagocytosis and actin reorganization. Blockage of PKA signal by MDL-12330A decreased CRH or UCN-promoted p-RhoA and p-Rac1 expressions. Blockage of PKC signal by cholerythine choride decreased CRH or UCN-promoted p-Rac1 expression and UCN-promoted p-RhoA expression, but increased the CRH-induced p-RhoA expression. ERK1/2 was also activated and served as upstream factor of RhoA/Rac1 signal pathway. SIGNIFICANCE: The results reveal that CRH and UCN promote phagocytosis of rat macrophages through convergent but dissociable pathways. PKA/PKC-ERK1/2-RhoA/Rac1 signal pathway plays an essential role in CRH- and UCN-enhanced phagocytosis.
Assuntos
Hormônio Liberador da Corticotropina/farmacologia , Hormônios/farmacologia , Macrófagos/metabolismo , Fagocitose/fisiologia , Transdução de Sinais/efeitos dos fármacos , Urocortinas/farmacologia , Animais , Western Blotting , Células Cultivadas , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Feminino , Citometria de Fluxo , Técnicas Imunoenzimáticas , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Masculino , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Fagocitose/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Proteína Quinase C/metabolismo , Ratos , Ratos Sprague-Dawley , Proteínas rac1 de Ligação ao GTP/metabolismo , Proteína rhoA de Ligação ao GTP/metabolismoRESUMO
Osteoblast L-type voltage-dependent calcium channels (VDCC) play important roles in maintaining intracellular homeostasis and influencing multiple cellular processes. In particular, they contribute to the activities and functions of osteoblasts (OBs). In order to study how L-type VDCC modulate calcium ion (Ca(2+)) homeostasis and the expression of osteogenic transcription factors in OBs exposed to fluoride, MC3T3-E1 cells were exposed to a gradient of concentrations of fluoride (0, 2.0, 5.0, 10.0 mg/L) in combination with 10 µM nifedipine, a specific inhibitor of VDCC, for 48 h. We examined messenger RNA (mRNA) and protein levels of Cav1.2, the main subunit of VDCC, and c-fos, c-jun, runt-related transcription factor 2 (Runx2), osterix (OSX), and intracellular free Ca(2+) ([Ca(2+)]i) concentrations in MC3T3-E1 cells. Our results showed that [Ca(2+)]i levels increased in a dose-dependent manner with increase in concentration of fluoride. Meantime, results indicated that lower concentrations of fluoride (less than 5 mg/L, especially 2 mg/L) can lead to high expression of Cav1.2 and enhance osteogenic function, while high concentration of fluoride (10 mg/L) can induce decreased Cav1.2 and osteogenic transcriptional factors in MC3T3E1 cells exposed to fluoride. However, the levels of [Ca(2+)]i, Cav1.2, c-fos, c-jun, Runx2, and OSX induced by fluoride were significantly altered and even reversed in the presence of nifedipine. These results demonstrate that L-type calcium channels play a crucial role in Ca(2+) homeostasis and they affect the expression of osteogenic transcription factors in fluoride-treated osteoblasts.
Assuntos
Cálcio/metabolismo , Fluoretos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Osteoblastos/efeitos dos fármacos , Fatores de Transcrição/genética , Animais , Canais de Cálcio Tipo L/metabolismo , Linhagem Celular , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Homeostase/efeitos dos fármacos , Camundongos , Nifedipino/farmacologia , Osteoblastos/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Fator de Transcrição Sp7 , Fatores de Transcrição/metabolismoRESUMO
BACKGROUND/AIMS: Acute kidney injury (AKI) during septic shock, which is one of the most common clinical syndromes in the intensive care unit (ICU), has a high mortality rate and poor prognosis, partly because of a poor understanding of the pathogenesis of renal dysfunction during septic shock. Although ischemic injury of the kidney has been reported to result from adenosine triphosphate (ATP) depletion, increasing evidence has demonstrated that AKI occurs in the absence of renal hypoperfusion and even occurs during normal or increased renal blood flow (RBF); nevertheless, whether energy metabolism disorder is involved in septic AKI and whether it changes according to renal hemodynamics have not been established. Moreover, tubular cell apoptosis, which is closely related to ATP depletion, rather than necrosis, has been shown to be the major form of cell injury during AKI. METHODS: We used canine endotoxin shock models to investigate the hemodynamics, renal energy metabolism, renal oxygen metabolism, and pathological changes during septic AKI and to explore the underlying mechanisms of septic AKI. RESULTS: The present results revealed that the nicotinamide adenine dinucleotide (NAD+) pool and the ATP/adenosine diphosphate (ADP) ratio were significantly decreased during the early phase of septic AKI, which is accompanied by a decreased renal oxygen extraction ratio (O2ER%) and decreased renal oxygen consumption (VO2). Furthermore, significant apoptosis was observed following renal dysfunction. RBF and renal oxygen delivery were not significantly altered. CONCLUSION: These results suggest that imbalanced energy metabolism, rather than tubular cell apoptosis, may be the initiator of renal dysfunction during septic shock.