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1.
Emerg Microbes Infect ; 9(1): 1123-1130, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32475230

RESUMO

Since the outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, it has rapidly spread across many other countries. While the majority of patients were considered mild, critically ill patients involving respiratory failure and multiple organ dysfunction syndrome are not uncommon, which could result death. We hypothesized that cytokine storm is associated with severe outcome. We enrolled 102 COVID-19 patients who were admitted to Renmin Hospital (Wuhan, China). All patients were classified into moderate, severe and critical groups according to their symptoms. 45 control samples of healthy volunteers were also included. Inflammatory cytokines and C-Reactive Protein (CRP) profiles of serum samples were analyzed by specific immunoassays. Results showed that COVID-19 patients have higher serum level of cytokines (TNF-α, IFN-γ, IL-2, IL-4, IL-6 and IL-10) and CRP than control individuals. Within COVID-19 patients, serum IL-6 and IL-10 levels are significantly higher in critical group (n = 17) than in moderate (n = 42) and severe (n = 43) group. The levels of IL-10 is positively correlated with CRP amount (r = 0.41, P < 0.01). Using univariate logistic regression analysis, IL-6 and IL-10 are found to be predictive of disease severity and receiver operating curve analysis could further confirm this result (AUC = 0.841, 0.822 respectively). Our result indicated higher levels of cytokine storm is associated with more severe disease development. Among them, IL-6 and IL-10 can be used as predictors for fast diagnosis of patients with higher risk of disease deterioration. Given the high levels of cytokines induced by SARS-CoV-2, treatment to reduce inflammation-related lung damage is critical.

2.
Clin Chim Acta ; 508: 110-114, 2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32405080

RESUMO

BACKGROUND: We observe changes of the main lymphocyte subsets (CD16+CD56、CD19、CD3、CD4、and CD8) in COVID-19-infected patients and explore whether the changes are associated with disease severity. METHODS: One-hundred and fifty-four cases of COVID-19-infected patients were selected and divided into 3 groups (moderate group, severe group and critical group). The flow cytometry assay was performed to examine the numbers of lymphocyte subsets. RESULTS: CD3+, CD4+ and CD8 + T lymphocyte subsets were decreased in COVID-19-infected patients. Compared with the moderate group and the sever group, CD3+, CD4+ and CD8+ T cells in the critical group decreased greatly (P < 0.001, P = 0.005 or P = 0.001). CONCLUSIONS: Reduced CD3+, CD4+, CD8+ T lymphocyte counts may reflect the severity of the COVID-19. Monitoring T cell changes has important implications for the diagnosis and treatment of severe patients who may become critically ill.

3.
J Hepatol ; 2020 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-32461121

RESUMO

BACKGROUD & AIMS: A substantial proportion of non-coding RNAs (ncRNAs) with small open reading frames (smORFs) are indeed translated to short peptides. It is unclear where and how short peptides promote hepatocellular carcinoma (HCC) development. METHODS: We performed RNA-immunoprecipitation followed by high-throughput sequencing (RIP-seq) assay with an antibody against ribosomal protein S6 (RPS6) on four cancer cell lines. Focusing on one lncRNA, LINC00998, we used qPCR and public databases to evaluate its expression level in HCC patients. Special vectors were constructed to confirm its coding potential. We also explored the function and mechanism of LINC00998-encoded peptide in tumor growth and metastasis. RESULTS: We discovered lots of lncRNAs binding to RPS6 in cancer cells. One of these lncRNAs, LINC00998, encoded one small endogenous peptide, termed SMIM30. SMIM30, rather than the RNA itself, promoted the HCC tumorigenesis by modulating cell proliferation and migration and its level was correlated with the poor survival rate of HCC patients. Furthermore, SMIM30 was transcribed by c-Myc and then drove the membrane anchoring of non-receptor tyrosine kinases-SRC/YES1. Moreover, the downstream MAPK signaling pathway was activated by SRC/YES1. CONCLUSIONS: Our results not only unravel a new mechanism of HCC tumorigenesis promoted by ncRNA-encoded peptides, but also suggest that the peptides can serve as a new target for HCC cancer therapy and a new biomarker for HCC diagnosis and prognosis.

4.
J Med Virol ; 2020 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-32232979

RESUMO

An outbreak of severe acute respiratory syndrome novel coronavirus (SARS-CoV-2) epidemic spreads rapidly worldwide. SARS-CoV-2 infection caused mildly to seriously and fatally respiratory, enteric, cardiovascular, and neurological diseases. In this study, we detected and analyzed the main laboratory indicators related to heart injury, creatine kinase isoenzyme-MB (CK-MB), myohemoglobin (MYO), cardiac troponin I (ultra-TnI), and N-terminal pro-brain natriuretic peptide (NT-proBNP), in 273 patients with COVID-19 and investigated the correlation between heart injury and severity of the disease. It was found that higher concentration in venous blood of CK-MB, MYO, ultra-TnI, and NT-proBNP were associated with the severity and case fatality rate of COVID-19. Careful monitoring of the myocardiac enzyme profiles is of great importance in reducing the complications and mortality in patients with COVID-19.

5.
Clin Chem Lab Med ; 2020 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-32286242

RESUMO

Background Among patients with coronavirus disease 2019 (COVID-19), the cases of a significant proportion of patients are severe. A viral nucleic acid test is used for the diagnosis of COVID-19, and some hematological indicators have been used in the auxiliary diagnosis and identification of the severity of COVID-19. Regarding body fluid samples, except for being used for nucleic acid testing, the relationship between COVID-19 and routine body fluid parameters is not known. Our aim was to investigate the value of urine biochemical parameters in the prediction of the severity of COVID-19. Methods A total of 119 patients with COVID-19 were enrolled at Renmin Hospital of Wuhan University. According to the severity of COVID-19, the patients were divided into three groups (moderate 67, severe 42 and critical 10), and 45 healthy persons were enrolled in the same period as healthy controls. The relationship between the results of urine biochemical parameters and the severity of COVID-19 was analyzed. Results The positive rates of urine occult blood (BLOOD) and proteinuria (PRO) were higher in COVID-19 patients than in healthy controls (p < 0.05); the urine specific gravity (SG) value was lower in patients than in healthy controls (p < 0.05), and the urine potential of hydrogen (pH) value was higher in patients than in healthy controls (p < 0.01). The positive rates of urine glucose (GLU-U) and PRO in the severe and critical groups were higher than those in the moderate group (p < 0.01 and p < 0.05, respectively); other biochemical parameters of urine were not associated with the severity of COVID-19. Conclusions Some urine biochemical parameters are different between patients with severe acute respiratory syndrome (SARS)-CoV-2 and healthy controls, and GLU-U and PRO may be helpful for the differentiation of COVID-19 severity.

6.
Clin Chem Lab Med ; 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32172226

RESUMO

Background As the number of patients increases, there is a growing understanding of the form of pneumonia sustained by the 2019 novel coronavirus (SARS-CoV-2), which has caused an outbreak in China. Up to now, clinical features and treatment of patients infected with SARS-CoV-2 have been reported in detail. However, the relationship between SARS-CoV-2 and coagulation has been scarcely addressed. Our aim is to investigate the blood coagulation function of patients with SARS-CoV-2 infection. Methods In our study, 94 patients with confirmed SARS-CoV-2 infection were admitted in Renmin Hospital of Wuhan University. We prospectively collect blood coagulation data in these patients and in 40 healthy controls during the same period. Results Antithrombin values in patients were lower than that in the control group (p < 0.001). The values of D-dimer, fibrin/fibrinogen degradation products (FDP), and fibrinogen (FIB) in all SARS-CoV-2 cases were substantially higher than those in healthy controls. Moreover, D-dimer and FDP values in patients with severe SARS-CoV-2 infection were higher than those in patients with milder forms. Compared with healthy controls, prothrombin time activity (PT-act) was lower in SARS-CoV-2 patients. Thrombin time in critical SARS-CoV-2 patients was also shorter than that in controls. Conclusions The coagulation function in patients with SARS-CoV-2 is significantly deranged compared with healthy people, but monitoring D-dimer and FDP values may be helpful for the early identification of severe cases.

7.
Clin Chim Acta ; 505: 172-175, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32156607

RESUMO

BACKGROUND: There's an outbreak of a novel coronavirus (SARS-CoV-2) infection since December 2019, first in China, and currently with more than 80 thousand confirmed infection globally in 29 countries till March 2, 2020. Identification, isolation and caring for patients early are essential to limit human-to-human transmission including reducing secondary infections among close contacts and health care workers, preventing transmission amplification events. The RT-PCR detection of viral nucleic acid test (NAT) was one of the most quickly established laboratory diagnosis method in a novel viral pandemic, just as in this COVID-19 outbreak. METHODS: 4880 cases that had respiratory infection symptoms or close contact with COVID-19 patients in hospital in Wuhan, China, were tested for SARS-CoV-2 infection by use of quantitative RT-PCR (qRT-PCR) on samples from the respiratory tract. Positive rates were calculated in groups divided by genders or ages. RESULTS: The positive rate was about 38% for the total 4880 specimens. Male and older population had a significant higher positive rates. However, 57% was positive among the specimens from the Fever Clinics. Binary logistic regression analysis showed that age, not gender, was the risk factor for SARS-CoV-2 infection in fever clinics. CONCLUSIONS: Therefore, we concluded that viral NAT played an important role in identifying SARS-CoV-2 infection.


Assuntos
Betacoronavirus/química , Infecções por Coronavirus/diagnóstico , DNA Viral/análise , Pneumonia Viral/diagnóstico , Reação em Cadeia da Polimerase em Tempo Real/métodos , Adolescente , Adulto , Fatores Etários , Idoso , Líquido da Lavagem Broncoalveolar/virologia , China/epidemiologia , Técnicas de Laboratório Clínico , Infecções por Coronavirus/epidemiologia , Surtos de Doenças , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nucleocapsídeo/química , Nucleocapsídeo/genética , Pandemias , Pneumonia Viral/epidemiologia , Sistema Respiratório/virologia , Fatores de Risco , Fatores Sexuais , Escarro/virologia , Adulto Jovem
8.
Chem Commun (Camb) ; 56(19): 2933-2936, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32040106

RESUMO

We developed a novel enzyme-free amplified SERS immunoassay by combining silver nanoparticle (AgNP)-linked immunoreaction and SERS transduction for the detection of disease biomarkers. As a proof of concept, our method was successfully illustrated with the disease biomarker α-fetoprotein with the detection limit of 3.3 × 10-13 g mL-1 and a double-blind experiment consisting of tens of serum samples was performed to confirm its reliability.


Assuntos
Imunoensaio/métodos , Análise Espectral Raman/métodos , Biomarcadores/sangue , Método Duplo-Cego , Humanos , Limite de Detecção , Nanopartículas Metálicas/química , Estudo de Prova de Conceito , Reprodutibilidade dos Testes , Prata/química
9.
Life Sci ; 242: 117247, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31899223

RESUMO

AIMS: Programmed death ligand 1 (PD-L1, CD274) has been reported to be expressed abnormally in many cancers, nevertheless, effect of PD-L1 on tumor cells remains unclear, especially in gastric cancer (GC). This study aimed to investigate the role of PD-L1 in metastasis and differentiation in GC. MAIN METHODS: Immunohistochemistry was performed on 237 paired GC tissues. shPD-L1 cells were generated by lentivirus shRNA solution and PD-L1-overexpressing cells were constructed by pcDNA3.1. Expression of PD-L1 and E-cadherin in GC cells were detected by western blot. KEY FINDINGS: PD-L1 expression was significantly lower in GC than that in adjacent normal tissues, especially in poorly differentiated and metastatic GC, but was positively correlated to survival time of patients. Moreover, PD-L1 ablation could decrease E-cadherin expression, promote cell migration and wound repair ability. In turn, overexpression of PD-L1 increased E-cadherin expression and inhibited wound repair ability. At the same time, All-trans retinoic acid (ATRA), which has the properties of pro-differentiation and inhibition of invasion and metastasis, upregulated the expression of PD-L1 and E-cadherin. SIGNIFICANCE: These findings not only identify PD-L1 may have a positive role for the treatment of GC, but also implicate that ATRA combined PD-L1 antibody drugs may enhance anti-tumor Immunity in GC.


Assuntos
Antígeno B7-H1/metabolismo , Neoplasias Gástricas/patologia , Antígeno B7-H1/fisiologia , Western Blotting , Caderinas/metabolismo , Linhagem Celular Tumoral , Técnicas de Silenciamento de Genes , Humanos , Neoplasias Gástricas/metabolismo
10.
Int Immunopharmacol ; 78: 106049, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31830624

RESUMO

AIMS: Sepsis is defined as a life-threatening organ dysfunction that is caused by a dysregulated host response to infection. Although much progress has been made in understanding the pathophysiology of sepsis, further discussion and study of the detailed therapeutic mechanisms are needed. Autophagy and endoplasmic reticulum stress are two pathways of the complicated regulatory network of sepsis. Herein, we focus on the cellular mechanism in which autophagy and endoplasmic reticulum stress participate in hydrogen (H2)-protected sepsis-induced organ injury. MATERIALS AND METHODS: Male C57BL/6 mice were randomly divided into the following groups: control group, cecal ligation puncture (CLP) group, CLP + tunicamycin(TM) group, CLP + 4-phenyl butyric acid (4-PBA) group, CLP + rapamycin (Rap) group, CLP + 3-methyladenine (3-MA) group, CLP + H2 group, CLP + H2 + 3-MA group, and CLP + H2 + TM group. After the experiment was completed, autophagosome was detected by transmission electron microscopy; protein PKR-like ER kinase (PERK), p-PERK, Eukaryotic translation initiation factor-2α (eIF2α), p-eIF2α, inositol-requiring enzyme1α(IRE1α), C/EBP homologous protein(CHOP), activating transcription factor(ATF), XBP-1, microtubule-associated protein 1 light(LC3), Beclin1, PTEN-induced putative kinase 1(PINK1), Parkin, and p65 subunit of Nuclear factor kappa B(NF-κb) were measured by Western blot; myeloperoxidase(MPO) activity in lung, bronchoalveolar lavage(BAL) total protein, lung wet-to-dry(W/D) ratio, serum biochemical indicators, 7-day survival rate, and pathological injury scores of lung, liver, and kidney were tested; and cytokines tumor necrosis factor-α(TNF-α), Interleukin(IL)-1ß, and IL-6 and high mobility group box protein (HMGB)1 were detected by enzyme-linked immunosorbent assay(ELISA). RESULTS: We demonstrated that sepsis induced endoplasmic reticulum stress. Moreover, it was found that an increase in endoplasmic reticulum impaired autophagy activity in sepsis, and the absence of endoplasmic reticulum stress attenuated tissue histological injury and dysfunction of lung, liver, and kidney in septic mice. Intriguingly, hydrogen alleviated the endoplasmic reticulum stress via the autophagy pathway and also mitigated inflammation and organ injury. CONCLUSION: Hydrogen provided protection from organ injury induced by sepsis via autophagy activation and endoplasmic reticulum stress pathway inactivation.

11.
Nature ; 577(7788): 109-114, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31827280

RESUMO

Activation of RIPK1 controls TNF-mediated apoptosis, necroptosis and inflammatory pathways1. Cleavage of human and mouse RIPK1 after residues D324 and D325, respectively, by caspase-8 separates the RIPK1 kinase domain from the intermediate and death domains. The D325A mutation in mouse RIPK1 leads to embryonic lethality during mouse development2,3. However, the functional importance of blocking caspase-8-mediated cleavage of RIPK1 on RIPK1 activation in humans is unknown. Here we identify two families with variants in RIPK1 (D324V and D324H) that lead to distinct symptoms of recurrent fevers and lymphadenopathy in an autosomal-dominant manner. Impaired cleavage of RIPK1 D324 variants by caspase-8 sensitized patients' peripheral blood mononuclear cells to RIPK1 activation, apoptosis and necroptosis induced by TNF. The patients showed strong RIPK1-dependent activation of inflammatory signalling pathways and overproduction of inflammatory cytokines and chemokines compared with unaffected controls. Furthermore, we show that expression of the RIPK1 mutants D325V or D325H in mouse embryonic fibroblasts confers not only increased sensitivity to RIPK1 activation-mediated apoptosis and necroptosis, but also induction of pro-inflammatory cytokines such as IL-6 and TNF. By contrast, patient-derived fibroblasts showed reduced expression of RIPK1 and downregulated production of reactive oxygen species, resulting in resistance to necroptosis and ferroptosis. Together, these data suggest that human non-cleavable RIPK1 variants promote activation of RIPK1, and lead to an autoinflammatory disease characterized by hypersensitivity to apoptosis and necroptosis and increased inflammatory response in peripheral blood mononuclear cells, as well as a compensatory mechanism to protect against several pro-death stimuli in fibroblasts.

12.
Neurosurgery ; 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31435649

RESUMO

BACKGROUND: Thin-walled regions (TWRs) of aneurysm surfaces observed in microscopic surgery are thought to be vulnerable areas for growth and rupture of unruptured intracranial aneurysms (UIAs). OBJECTIVE: To identify hemodynamic features of TWRs of aneurysms by using computational fluid dynamics (CFD) analyses of unruptured middle cerebral artery bifurcation (MCAB) aneurysms. METHODS: Nine patients with 11 MCAB aneurysms were enrolled, and their TWRs were identified. CFD analysis was performed using 3 parameters: pressure, wall shear stress (WSS), and WSS divergence (WSSD). Each parameter was evaluated for its correspondence with TWR. RESULTS: Among 11 aneurysms, 15 TWRs were identified. Corresponding matches with CFD parameters (pressure, WSS, and WSSD) were 73.33, 46.67, and 86.67%, respectively. CONCLUSION: WSSD, a hemodynamic parameter that accounts for both magnitude and directionality of WSS, showed the highest correspondence. High WSSD might correspond with TWR of intracranial aneurysms, which are likely high-risk areas for rupture.

14.
Mar Drugs ; 17(8)2019 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-31357680

RESUMO

Overexpression of the global regulator LaeA in a marine-derived fungal strain of Penicillium dipodomyis YJ-11 induced obvious morphological changes and metabolic variations. Further chemical investigation of the mutant strain afforded a series of sorbicillinoids including two new ones named 10,11-dihydrobislongiquinolide (1) and 10,11,16,17-tetrahydrobislongiquinolide (2), as well as four known analogues, bislongiquinolide (3), 16,17-dihydrobislongiquinolide (4), sohirnone A (5), and 2',3'-dihydrosorbicillin (6). The results support that the global regulator LaeA is a useful tool in activating silent gene clusters in Penicillium strains to obtain previously undiscovered compounds.


Assuntos
Organismos Aquáticos/genética , Organismos Aquáticos/metabolismo , Produtos Biológicos/metabolismo , Fungos/genética , Fungos/metabolismo , Penicillium/genética , Penicillium/metabolismo , Genes Fúngicos/genética , Mutação/genética
15.
Biomed Res Int ; 2019: 9321494, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31240230

RESUMO

Objective: Hepatitis B virus (HBV) causes inflammation of the liver and is the leading cause of both liver cirrhosis (LC) and hepatocellular carcinoma (HCC). Serine protease inhibitor Kazal type 1 (SPINK1) is an acute-phase response protein that is overexpressed in liver cancer tissue. This study investigated the clinical value of SPINK1 with regard to the diagnosis of HBV-related diseases and its regulatory mechanism. Methods: Serum levels of SPINK1 in HBV-infected patients and healthy participants were detected by enzyme-linked immunosorbent assay (ELISA). Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and western blotting were used to detect differential expression of SPINK1 mRNA and protein in HepG2 and HepG2.2.15 cells. The HBV infectious clone pHBV1.3 and its individual genes were cotransfected into HepG2 cells with the SPINK1 promoter coupled to a luciferase reporter; luciferase activity was measured, and the expression levels of SPINK1 were examined. Results: Serum SPINK1 levels of HBV-infected patients were significantly higher than those of healthy participants, and the serum levels of SPINK1 in patients who tested positive for HBeAg were significantly higher than those in patients who tested negative for HBeAg. The serum SPINK1 levels of patients with LC or HCC were markedly higher than those of patients with chronic hepatitis. The HBV X protein (HBx) activated the SPINK1 promoter to upregulate expression of SPINK1 at both mRNA and protein levels. Conclusions: HBV enhances expression of SPINK1 through X. SPINK1 levels are increased during progression of HBV-related diseases and might be utilized as a biomarker for the diagnosis of HBV-related diseases.


Assuntos
Progressão da Doença , Vírus da Hepatite B/patogenicidade , Hepatite B/metabolismo , Transativadores/efeitos adversos , Inibidor da Tripsina Pancreática de Kazal/efeitos dos fármacos , Inibidor da Tripsina Pancreática de Kazal/metabolismo , Adulto , Carcinoma Hepatocelular/patologia , Feminino , Células Hep G2 , Antígenos E da Hepatite B , Humanos , Fígado/patologia , Cirrose Hepática/patologia , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Regiões Promotoras Genéticas , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Inibidor da Tripsina Pancreática de Kazal/sangue , Inibidor da Tripsina Pancreática de Kazal/genética , Regulação para Cima
16.
Int J Cardiovasc Imaging ; 35(1): 185-193, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30128848

RESUMO

Computed tomography angiography (CCTA)-based calculations of fractional flow reserve (FFR) can improve the diagnostic performance of CCTA for physiologically significant stenosis but the computational resource requirements are high. This study aimed at establishing a simple and efficient algorithm for computing simulated FFR (S-FFR). A total of 107 patients who underwent CCTA and invasive FFR measurements were enrolled in the study. S-FFR was calculated using 145 evaluable coronary arteries with off-the-shelf softwares. FFR ≤ 0.80 was a reference threshold for diagnostic performance of diameter stenosis (DS) ≥ 50%, DS ≥ 70%, or S-FFR ≤ 0.80. FFR ≤ 0.80 was identified in 78 vessels (54%). In per-vessel analysis, S-FFR showed good correlation (r = 0.83) and agreement (mean difference = 0.02 ± 0.08) with FFR. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of S-FFR ≤ 0.80 for FFR ≤ 0.80 were 84%, 92%, 92%, 83%, and 88%, respectively. S-FFR ≤ 0.80 showed much higher predictive performance for FFR ≤ 0.80 compared with DS ≥ 50% or DS ≥ 70% (c-statistics = 0.92 vs. 0.58 or 0.65, p < 0.001, all). The classification agreement between FFR and S-FFR was > 80% when the average of FFR and S-FFR was < 0.76 or > 0.86. Per-patient analysis showed consistent results. In this study, a simple and computationally efficient simulated FFR (S-FFR) algorithm is designed and tested using non-proprietary off-the-shelf software. This algorithm may expand the accessibility of clinical applications for non-invasive coronary physiology study.


Assuntos
Algoritmos , Angiografia por Tomografia Computadorizada/métodos , Angiografia Coronária/métodos , Estenose Coronária/diagnóstico por imagem , Vasos Coronários/diagnóstico por imagem , Reserva Fracionada de Fluxo Miocárdico , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Idoso , Estenose Coronária/fisiopatologia , Vasos Coronários/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos , Índice de Gravidade de Doença
17.
Sci Rep ; 8(1): 4692, 2018 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-29549347

RESUMO

Invasive procedure is a prerequisite for studying coronary physiology. We established the measurement of non-invasive physiological parameters including coronary blood flow (CBF), flow velocity, and microvascular resistance using coronary computed tomography angiography (CCTA). Vessel-specific CBF was derived from transluminal attenuation flow encoding (TAFE) and then tested using three separate datasets consisted of computational simulation, human perfusion CT, and human CCTA. TAFE-derived CBF correlated well with measured vessel-specific myocardial blood flow and CBF. TAFE-derived CBF per myocardial mass consistently decreased with the progressive severity of stenosis, and it was found to better to detect significant stenosis than transluminal attenuation gradient (TAG). With the addition of vessel anatomy, TAFE-derived CBF could calculate flow velocity and microvascular resistance. The results of non-invasively acquired parameters according to the severity of stenosis were similar to those obtained through invasive physiology studies. Our study demonstrated that non-invasive comprehensive coronary physiology parameters can be derived from CCTA without any pre-specified condition or performing complex heavy computational processes. Our findings are expected to expand the clinical coverage of CCTA and coronary physiology.


Assuntos
Biologia Computacional/métodos , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/fisiologia , Angiografia por Tomografia Computadorizada , Angiografia Coronária , Feminino , Humanos , Masculino , Modelos Cardiovasculares , Imagem de Perfusão do Miocárdio/métodos , Fluxo Sanguíneo Regional
19.
Breast Cancer ; 25(4): 431-437, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29388117

RESUMO

BACKGROUND: The genotype of Fanconi Anemia complementation group M (FANCM) was previously found to be associated with breast cancer risk in several populations. Here, we studied the expression of FANCM and its correlation with clinical characteristics in Chinese patients with breast cancer. METHODS: We performed an immunohistochemical study of FANCM protein in clinical breast cancer tissues from 310 patients along with 44 adjacent tissues. RESULTS: FANCM protein level is lower in triple-negative breast cancer tissues than in other subtypes (P = 0.008). In addition, high FANCM expression correlated with pathology type IDC (P = 0.040), estrogen receptor positive (P < 0.001), progesterone receptor positive (P = 0.001), and low Ki-67 status (P = 0.003). Multivariate analysis revealed that FANCM status was an independent prognostic factor for overall survival (P = 0.017) in luminal B breast cancer. CONCLUSIONS: FANCM levels are significantly associated with different subtypes of human breast cancer. Specifically, FANCM could play a role in the progression of luminal B breast cancer.


Assuntos
Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , DNA Helicases/metabolismo , Grupo com Ancestrais do Continente Asiático , Neoplasias da Mama/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/mortalidade , Neoplasias de Mama Triplo Negativas/patologia
20.
J Cell Biochem ; 119(4): 3220-3235, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29091308

RESUMO

This study aimed to investigate the effect of parathyroid hormone (PTH1-34) on osteogenic and adipogenic differentiation of hBMSCs by the regulation of miR-155. A total of 36 adult volunteers were selected in this study. Effects of PTH1-34 on the proliferation of hBMSCs and miR-155 expression were investigated using a MTT assay. The hBMSCs were divided into blank, PTH1-34, miR-155 mimic, miR-155 mimic negative control (NC), miR-155 inhibitor, miR-155 inhibitor NC, PTH1-34 + miR-155 mimic, PTH1-34 + miR-155 inhibitor, and NPS R-568 groups. Postmenopausal osteoporosis (PMOP) mouse models were established by ovariectomy (OVX) and divided into ten groups. The RT-qPCR and Western blotting assay were carried out to detect the expression of osteogenesis/adipogenic-related genes and miR-155, and osteogenesis/adipogenic-related proteins. PTH1-34 could promote hBMSCs proliferation and inhibit miR-155 expression in a dose-dependent manner. Compared with the blank control group, expressions of Runx2, and BSP was up-regulated in the PTH1-34 and miR-155 inhibitor groups, while expressions of miR-155, PPAR-γ, lipoprotein lipase (LPL), fatty acid binding protein 4 (Fabp4), adiponectin, and CCAAT/enhancer binding protein α (C/EBPα) were down-regulated. In the in vivo experiment, compared with the OVX group, the BMD and expressions of Runx2 and BSP was up-regulated in the PTH1-34, miR-155 inhibitor, and PTH1-34 + miR-155 inhibitor groups, while expressions of PPAR-γ, LPL, Fabp4, adiponectin, and C/EBPα were down-regulated. The miR-155 mimic and NPS R-568 groups followed opposite trends. PTH1-34 could promote the osteogenic differentiation and inhibits adipogenic differentiation of hBMSCs through down-regulating miR-155 in PMOP mice.


Assuntos
Tecido Adiposo/citologia , Células-Tronco Mesenquimais/citologia , MicroRNAs/genética , Osteogênese/efeitos dos fármacos , Osteoporose Pós-Menopausa/genética , Hormônio Paratireóideo/administração & dosagem , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Adulto , Animais , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Regulação para Baixo , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Camundongos , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/metabolismo , Hormônio Paratireóideo/farmacologia
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