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In order to assess the electromagnetic exposure safety of passengers under the civil communication system of the subway, the radio-frequency (RF) electromagnetic environment of subway carriage is established by using COMSOL Multiphysics software, it includes a 1-1/4 " leaky coaxial cable (LCX1) and a 1-5/8" leaky coaxial cable (LCX2), which are designed to be the exposure sources, and twelve passengers at different position. The electromagnetic environment model has been verified through field measurement. The exposure dose distribution of twelve passengers is compared and analyzed, when LCX1 and LCX2 works respectively. The simulated results show that, to compare with LCX2, the electromagnetic dose absorbed by the passengers is reduced by 9.19% and 22.50% at 2100 MHz and 2600 MHz respectively. The specific absorption rate (SAR) of passengers obtains the maximum value of 1.91×10-4 W/Kg and the temperature rise to 0.214 K when the LCX1 works at 3400 MHz. By comparing with the public exposure limitation of the International Commission of Non-Ionizing Radiation Protection (ICNIRP), it demonstrates the electromagnetic exposure safety of the passengers under the civil communication system. More importantly, the proposed LCX1 not only could add the 5G signal cover but also lower the SAR absorbed by the passengers, which indicates that the public electromagnetic exposure dose could be reduced by adjusting the radiation performances of exposure source, which provide a new way for electromagnetic protecting.
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Campos Eletromagnéticos , Ferrovias , Campos Eletromagnéticos/efeitos adversos , Ondas de Rádio/efeitos adversos , Temperatura , ComunicaçãoRESUMO
Epicardial adipose tissue (EAT) is a metabolically active organ which generates inflammatory cytokines. Thickness of EAT is associated with onset and development of heart failure with preserved ejection fraction (HFpEF). However, it is still unclear the specific mechanisms and pharmacological targets on EAT induced inflammation in HFpEF. A two-hit protocol with western diet and Nω-nitrol-arginine methyl ester (L-NAME) was used to establish HFpEF mouse model. In HFpEF mice, inflammatory biomarkers, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and von willebrand factor (vWF) elevated in myocardium compared to control. Inflammatory cell infiltration in myocardium was increased. In HFpEF mice, inflammasome-mediated pyroptosis pathway was activated in the EAT. Suppression of pyroptosis-related protein gasdermin D (GSDMD) in cultured EAT could lower cardiomyocyte inflammation and autophagy. Furthermore, spironolactone and rosuvastatin, the two-hit anti-inflammatory agents, reduced NLR family pyrin domain containing 3 (NLRP3)/GSDMD pyroptosis in EAT and autophagy in myocardium of HFpEF mouse. The combination treatment also enhanced exercise tolerance and appeased inflammatory injuries in HFpEF mice. CONCLUSION: Pyroptosis signaling is involved in EAT-myocardium axis in mouse model of HFpEF. Targeting adipocyte-derived inflammation in EAT bears potential to treatment HFpEF.
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Insuficiência Cardíaca , Piroptose , Camundongos , Animais , Insuficiência Cardíaca/metabolismo , Volume Sistólico , Inflamassomos/metabolismo , Miocárdio/metabolismo , Tecido Adiposo/metabolismo , Inflamação/patologia , Modelos Animais de Doenças , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismoRESUMO
Background: Endothelial injury induced by low shear stress (LSS) is an initiating factor in the pathogenesis of various cardiovascular diseases, including atherosclerosis, hypertension, and thrombotic diseases. Low shear stress activates the mammalian target of rapamycin complex 2 (mTORC2) signaling pathway. Rictor, the main constituent protein of mTORC2, is involved in vascular development. However, the impact of conditional Rictor ablation on endothelial homeostasis, especially on endothelial-specific markers, such as vascular endothelial-cadherin (VE-cadherin) and von Willebrand factor (VWF), under blood flow stimulation is unclear. Objective: We aimed to investigate whether endothelial Rictor is involved in maintaining vascular endothelial integrity and the potential role of Rictor in atheroprone blood flow-mediated endothelial injury. Methods and results: Immunofluorescence staining showed that endothelial Rictor was successfully knocked out in a mouse model. Scanning electron microscopy (EM) detection revealed disruption of the endothelial monolayer in the thoracic aorta of Rictor-deficient mice. Furthermore, scanning electron microscopy and transmission electron microscopy showed that Rictor deletion disrupted endothelial integrity and expanded cell junctions in the left common carotid artery region. In vitro, low shear stress disrupted actin filament polarity and the promoted the translocation of vascular endothelial-cadherin, the key component of adherens junctions (AJs) in human umbilical vein endothelial cells. After Rictor downregulation by small interfering RNA, the translocation of vascular endothelial-cadherin and stress fibers increased. Rictor knockdown inhibited low shear stress-induced von Willebrand factor upregulation, and downregulation of vascular endothelial-cadherin decreased low shear stress-induced von Willebrand factor expression. These results suggest that vascular endothelial-cadherin/von Willebrand factor is a possible mechanism mediated by Rictor in the pathological process of low shear stress-induced endothelial injury. Conclusion: Rictor is a key protein that regulates endothelial integrity under vascular physiological homeostasis, and Rictor mediates low shear stress-induced endothelial injury by regulating adherens junctions and von Willebrand factor.
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DNA damage repair (DDR) is essential for maintaining genome integrity and modulating cancer risk, progression, and therapeutic response. DDR defects are common among non-small lung cancer (NSCLC), resulting in new challenge and promise for NSCLC treatment. Thus, a thorough understanding of the molecular characteristics of DDR in NSCLC is helpful for NSCLC treatment and management. Here, we systematically analyzed the relationship between DDR alterations and NSCLC prognosis, and successfully established and validated a six-DDR gene prognostic model via LASSO Cox regression analysis based on the expression of prognostic related DDR genes, CDC25C, NEIL3, H2AFX, NBN, XRCC5, RAD1. According to this model, NSCLC patients were classified into high-risk subtype and low-risk subtype, each of which has significant differences between the two subtypes in clinical features, molecular features, immune cell components, gene mutations, DDR pathway activation status and clinical outcomes. The high-risk patients was characterized with worse prognosis, lower proportion and number of DDR mutations, unique immune profile and responsive to immunetherapy. And the low-risk patients tend to have superior survival, while being less responsive to immunotherapy and more sensitive to treatment with DNA-damaging chemotherapy drugs. Overall, this molecular classification based on DDR expression profile enables hierarchical management of patients and personalized clinical treatment, and provides potential therapeutic targets for NSCLC.
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Vascular endothelial cells (ECs), derived from the mesoderm, form a single layer of squamous cells that covers the inner surface of blood vessels. In addition to being regulated by chemical signals from the extracellular matrix (ECM) and blood, ECs are directly confronted to complex hemodynamic environment. These physical inputs are translated into biochemical signals, dictating multiple aspects of cell behaviour and destination, including growth, differentiation, migration, adhesion, death and survival. Mechanosensors are initial responders to changes in mechanical environments, and the overwhelming majority of them are located on the plasma membrane. Physical forces affect plasma membrane fluidity and change of protein complexes on plasma membrane, accompanied by altering intercellular connections, cell-ECM adhesion, deformation of the cytoskeleton, and consequently, transcriptional responses in shaping specific phenotypes. Among the diverse forces exerted on ECs, shear stress (SS), defined as tangential friction force exerted by blood flow, has been extensively studied, from mechanosensing to mechanotransduction, as well as corresponding phenotypes. However, the precise mechanosensors and signalling pathways that determine atheroprone and atheroprotective phenotypes of arteries remain unclear. Moreover, it is worth to mention that some established mechanosensors of atheroprotective SS, endothelial glycocalyx, for example, might be dismantled by atheroprone SS. Therefore, we provide an overview of the current knowledge on mechanosensors in ECs for SS signals. We emphasize how these ECs coordinate or differentially participate in phenotype regulation induced by atheroprone and atheroprotective SS.
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Diaporthe sp. fungi is one of the important sources of active natural products. Polyketides, alkaloids, terpenes, anthraquinones and other types of novel metabolic products are found from this genus, and many of them have significant anti-tumor, antibacterial, anti-hyperlipidemia, inhibition of pulmonary fibrosis, antioxidant and other biological activities. This paper reviewed source, structure and biological activity of natural products from Diaporthe sp. in the past two decades, and provided a reference for in-depth study of natural product of this genus fungus and innovative drug development.
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Produtos Biológicos , Policetídeos , Antibacterianos , Produtos Biológicos/farmacologia , Fungos , TerpenosRESUMO
Laparoscopic cholecystectomy and percutaneous transhepatic gallbladder drainage (PTGBD) are common treatments for patients with acute cholecystitis. However, the safety and efficacy of emergency laparoscopic cholecystectomy (ELC) and delayed laparoscopic cholecystectomy (DLC) after PTGBD in patients with acute cholecystitis remain unclear. The PubMed, EMBASE, and Cochrane Library databases were searched through October 2019. The quality of the included nonrandomized studies was assessed using the Methodological Index for Nonrandomized Studies (MINORS). The meta-analysis was performed using STATA version 14.2. A random-effects model was used to calculate the outcomes. A total of fifteen studies involving 1780 patients with acute cholecystitis were included in the meta-analysis. DLC after PTGBD was associated with a shorter operative time (SMD - 0.51; 95% CI - 0.89 to - 0.13; P = 0.008), a lower conversion rate (RR 0.43; 95% CI 0.26 to 0.69; P = 0.001), less intraoperative blood loss (SMD - 0.59; 95% CI - 0.96 to - 0.22; P = 0.002) and longer time of total hospital stay compared to ELC (SMD 0.91; 95% CI 0.57-1.24; P < 0.001). There was no difference in the postoperative complications (RR 0.68; 95% CI 0.48-0.97; P = 0.035), biliary leakage (RR 0.65; 95% CI 0.34-1.22; P = 0.175) or mortality (RR 1.04; 95% CI 0.39-2.80; P = 0.933). Compared to ELC, DLC after PTGBD had the advantages of a shorter operative time, a lower conversion rate and less intraoperative blood loss.
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Colecistectomia Laparoscópica , Colecistite Aguda , Colecistectomia , Colecistite Aguda/cirurgia , Drenagem , Humanos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: To compare the outcome of biliary atresia (BA) patients with and without hilar cyst on preoperative ultrasound. METHODS: A single center retrospective review of patients of BA with (n = 27) and without hilar cyst (n = 27) over a 5 y period was done. The patients were analyzed using propensity score matching to reduce selection bias. All patients were diagnosed as type III BA by histologic examination and cholangiograms. Clinicopathological characteristics and survival outcomes were compared between the two groups. RESULTS: There were no significant intergroup differences between baseline characteristics and outcomes after Kasai portoenterostomy surgery in two groups. BA with hilar cyst group showed comparable survival outcomes to the BA without cyst group (cumulative 1-y, 2-y and 5-y overall survival rates with native liver 61.4% vs. 65.8%, P = 0.041; 45.0% vs. 49.0%, P = 0.57; 45.0% vs. 49.0%, P = 0.57). And the Kaplan-Meier survival curves showed no significant difference in cumulative survival with native liver between the two groups (P = 0.58). CONCLUSIONS: Type III BA with hilar cyst had no better prognosis compared with Type III BA without cyst.
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Atresia Biliar , Cistos , Atresia Biliar/complicações , Atresia Biliar/diagnóstico , Atresia Biliar/cirurgia , Cistos/cirurgia , Humanos , Lactente , Portoenterostomia Hepática , Prognóstico , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Background: The specific mechanism of cardiovascular and cerebrovascular vasculopathy in the context of end-stage renal disease has not been elucidated. In the present study, we investigated the clinical impact of myeloid-derived suppressor cells (MDSCs) on hemodialysis patients and their mechanism of action. Methods: MDSCs were tested among 104 patients undergoing hemodialysis and their association with overall survival (OS) and cardiovascular and cerebrovascular events was determined. Results: Hemodialysis patients presented a significantly higher level of monocytic MDSCs (M-MDSCs) compared to healthy controls. M-MDSC were tested 3 months after first testing among 103 hemodialysis patients, with one patient not retested due to early death. The repeated results of M-MDSC levels were consistent with the initial results. Patients with persistent high level of M-MDSCs presented decreased OS, as well as increased stroke and acute heart failure events. As illustrated by multivariate Cox regression, M-MDSC was an independent predictor for OS and stroke events of hemodialysis patients. T cell proliferations were significantly abrogated by hemodialysis-related M-MDSCs in a dose-dependent manner. Besides, M-MDSCs presented higher levels of CXCR4 and VLA-4 compared to monocytes, which indicated their enhanced capability to be recruited to atherosclerotic lesions. The expression of arginase I and activity of arginase was also significantly raised in hemodialysis-related M-MDSCs. Human coronary arterial endothelial cells (HCAECs) presented increased capability to migration by coculture with M-MDSCs, compared with monocyte group. Arginase inhibitor and L-arginine abrogated the immune suppressive function and induction of HCAECs migration of hemodialysis related M-MDSC. Plasma IFN-γ, TNF-α and IL-6 were elevated in hemodialysis patients compared with healthy control. M-MDSC level was positively related to IL-6 level among hemodialysis patients. The plasma of hemodialysis patients induced M-MDSCs significantly compared with plasma from health donors. Besides, IL-6 neutralizing antibody significantly abrogated the induction. Neutralizing antibody of IFN-γ and TNF-α partially decreased the generation of arginase of the induced M-MDSC. Conclusions: M-MDSCs were elevated in ESRD patients under hemodialysis, and they exhibited a strong association with the risk of cardiovascular and cerebrovascular diseases. Hemodialysis related M-MDSC presented enhanced recruitment to atherosclerotic lesions, promoted the migration of endothelial cells through exhaustion of local L-arginine.
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Doenças Cardiovasculares/epidemiologia , Transtornos Cerebrovasculares/epidemiologia , Células Endoteliais/fisiologia , Falência Renal Crônica/terapia , Células Supressoras Mieloides/imunologia , Anticorpos Bloqueadores , Arginase/metabolismo , Proliferação de Células , Células Cultivadas , Humanos , Interferon gama/metabolismo , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/mortalidade , Ativação Linfocitária , Diálise Renal , Análise de Sobrevida , Fator de Necrose Tumoral alfa/metabolismoRESUMO
OBJECTIVES: To measure the testicular volume and testicular fat deposition of middle-aged overweight men and to assess the utility of testicular fat deposition and testicular volume in determining and monitoring testicular infertility. MATERIALS AND METHODS: Pelvic MRI with thin slice T2WI, T1WI and mDIXON Quant was performed on 30 middle-aged overweight patients in the treatment group and 30 middle-aged overweight men in the control group. Testicular volume and testicular fat deposition were measured separately based on thin slice T2WI and the fat fraction (FF) map of mDIXON Quant, and the testicular fat deposition observed with T1WI was used as a reference for qualitative diagnosis. Testicular volume and testicular fat deposition in middle-aged overweight individuals were compared using a t test with Bonferroni correction and receiver operating characteristic (ROC) curve. RESULTS: The testicular volumes (10.6-17.9 cm3) of individuals in the treatment group were smaller than those (12.6-19.0 cm3) of individuals in the control group (p < 0.05), and the average FF value (2.2-4.6%) of the testes in the treatment group was higher than that (1.5-3.1%) in the control group (p < 0.05). The ROC analysis showed that the area under the curve (AUC) of testicular fat deposition (0.899) was higher than that of testicular volume (0.777), and biopsy and sperm count were used as references to diagnose infertility. The diagnostic sensitivity (90.00%) of testicular fat deposition of the mDIXON Quant sequence was higher than that (50.00%) of the T1W sequence (p < 0.05). Testicular fat deposition was decreased after 6 months of active treatment with exercise weight loss and drug treatment, and no significant change in testicular volume was observed 6 months later. CONCLUSION: The findings suggest that the proton density fat fraction (mDIXON Quant sequence in this study) approach is a novel tool for the quantitative and objective evaluation of testicular fat deposition. Testicular fat deposition measurement is more specific than testicular volume measurement in the diagnosis of male infertility, and the mDIXON Quant is more sensitive than T1WI in the diagnosis of testicular fat deposition. Furthermore, our findings may facilitate a more accurate diagnosis and monitoring of testicular infertility, therapeutic effect, and prognosis by measuring testicular fat deposition.
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Tecido Adiposo/diagnóstico por imagem , Infertilidade Masculina/fisiopatologia , Imageamento por Ressonância Magnética/métodos , Sobrepeso/fisiopatologia , Testículo/diagnóstico por imagem , Tecido Adiposo/fisiopatologia , Adulto , Área Sob a Curva , Humanos , Processamento de Imagem Assistida por Computador , Infertilidade Masculina/complicações , Masculino , Pessoa de Meia-Idade , Sobrepeso/complicações , Pelve , Curva ROC , Estudos Retrospectivos , Sensibilidade e Especificidade , Contagem de Espermatozoides , Motilidade dos Espermatozoides , Testículo/fisiopatologiaRESUMO
The prognosis of oral squamous cell carcinoma (OSCC) patients remains unclear, and a better understanding of the underlying molecular mechanisms is urgently required. Jumonji-C (JmjC) domain-containing protein 5 (JMJD5), renamed KDM8, has been implicated in tumorigenesis, circadian rhythm modulation, embryological development, and osteoclastogenesis. In the present study, we found that JMJD5 was over-expressed in patients with OSCC by real-time quantitative PCR (qPCR), western blot and immunohistochemical assays. When knockdown using small interfering RNA (siRNA) in OSCCs, JMJD5 was exhibited to be important for sustaining cell migration and invasion. JMJD5-knockdown increased E-cadherin expressions, and decreased N-cadherin and Vimentin expression levels in OSCC cells. Further, apoptosis was induced by JMJD5-silence through both the intrinsic and extrinsic pathways, as evidenced by the increased cleavage of Caspase-8/-9/-3 and PARP. Meanwhile, p53 expression levels were also up-regulated by JMJD5-knockdown. Suppressing p53 expressions with its inhibitor, PFTα, blocked apoptotic response in JMJD5-silenced cells. JMJD5 inhibition-induced decrease of nuclear factor-kappaB (NF-κB) was rescued by pifithrin-α (PFTα) pre-treatment. Consistently, over-expressing JMJD5 decreased p53, cleaved Caspase-3 and poly (ADP-ribose) polymerase-1 (PARP-1), whereas increased nuclear NF-κB expressions in OSCC cell lines. More importantly, targeting JMJD5 reduced xenograft tumor growth in vivo through the same molecular mechanisms evidenced in vitro. Thus, the data supplied mechanistic insights into the effects of JMJD5 on the modulation of OSCC development, illustrating that JMJD5 might be an essential prognostic indicator and therapeutic target against OSCC progression.
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Carcinoma de Células Escamosas/metabolismo , Regulação para Baixo/fisiologia , Histona Desmetilases/metabolismo , Neoplasias Bucais/metabolismo , NF-kappa B/fisiologia , Proteína Supressora de Tumor p53/metabolismo , Animais , Biomarcadores Tumorais/antagonistas & inibidores , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Técnicas de Silenciamento de Genes/métodos , Histona Desmetilases/antagonistas & inibidores , Humanos , Masculino , Camundongos , Camundongos Nus , NF-kappa B/antagonistas & inibidores , Invasividade Neoplásica/prevenção & controle , Transdução de Sinais/fisiologia , Carga Tumoral/fisiologia , Proteína Supressora de Tumor p53/antagonistas & inibidores , Ensaios Antitumorais Modelo de Xenoenxerto/métodosRESUMO
OBJECTIVE: To explore the expression and significance of neutrophil gelatinase-associated lipocalin(NGAL)in renal interstitial fibrosis (RIF) in rats. METHODS: A total of 60 male Sprague-Dawley rats were randomly divided into 3 groups of sham operation (SOR), unilateral ureteral obstruction (UUO) and angiotensin-converting enzyme inhibitor (ACEI). The serum concentrations of NGAL and tumor necrosis factor-alpha (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA). And the expressions of NGAL, matrix metalloproteinase-9 (MMP-9) and transforming growth factor-ß1 (TGF-ß1) were observed by immunohistochemistry. RESULTS: (1) The levels of serum NGAL and TNF-α in UUO group obviously increased as compared to those in ACEI and SOR groups (NGAL: (69.2 ± 5.6) vs (41.0 ± 10.4), (10.8 ± 3.8) pg/ml; TNF-α: (116.2 ± 9.2) vs (99.8 ± 14.0), (29.2 ± 5.7) ng/ml; all P < 0.05). (2) The expressions of NGAL, TGF-ß1 and MMP-9 in renal tubular epithelial cells of UUO group increased as compared to those in SOR group. The expression of TGF-ß1 in ACEI group was apparently less than that in UUO group. The protein levels of NGAL and MMP-9 in ACEI group were obviously lower than those in UUO group within Day 14 post-operation and significantly higher than those in UUO group at Days 21 and 28. (3) In UUO group, the level of NGAL was positively correlated with the serum levels of TNF-α and serum creatinine (r = 0.910, 0.673, P < 0.01). The expression of NGAL had a highly positive correlation with MMP-9 (r = 0.913, P < 0.01) and the index of interstitial damage and the degrees of TGF-ß1 at Days 3-7 post-operation(r = 0.937, 0.847, P < 0.01). And the expression of NGAL was negatively correlated with the index of interstitial damage and the degrees of TGF-ß1 at Days 14-28 post-operation (r = -0.945, -0.944, P < 0.01). CONCLUSION: The expression of NGAL significantly increases in UUO modal of rats. And it is closely correlated with MMP-9, TNF-α and TGF-ß1. ACEI may influence the biological effects of NGAL by suppressing inflammatory responses, down-regulating the expression of TGF-ß1 and regulating the expression and the activity of MMP-9.
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Proteínas de Fase Aguda/metabolismo , Lipocalinas/metabolismo , Nefrite Intersticial/metabolismo , Nefrite Intersticial/patologia , Proteínas Proto-Oncogênicas/metabolismo , Animais , Fibrose , Rim/patologia , Lipocalina-2 , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Ratos , Ratos Sprague-Dawley , Fator de Crescimento Transformador beta1/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
OBJECTIVES: To investigate the role of focal adhesion kinase (FAK) in the pathogenesis of cardiac hypertrophy induced by hypertension. METHODS: Using immunofluorescent labeling, confocal microscopy and Western blotting, the expression and subcellular localization of FAK in the cardiac myocytes of left ventricle were determined in 2, 6, 12, and 18 month-old rats with spontaneously hypertensive heart failure (SHHF) along with age-matched control Wistar-Kyoto (WKY) rats. RESULTS: There was no significant difference of FAK expression between 2 month-old SHHF and WKY rats (50.5+/-6.9 vs. 49.8+/-5.0, n=6, P>0.05). In contrast with the control groups, the expression of FAK significantly increased in 6, 12 and 18 month-old SHHF rats (130.6+/-3.0 vs. 47.3+/-1.3, 144.7+/-5.4 vs. 46.4+/-3.1, 141.4+/-9.8 vs. 48.5+/-2.2, each groups n=6, P<0.05) with FAK protein primarily cumulated in the intercalated disks and nuclei. CONCLUSIONS: FAK may play a role in the cell signaling transduction leading to cardiac hypertrophy, presumably through regulations of hypertrophic gene transcription and RNA processing.