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1.
J Affect Disord ; 260: 695-702, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31561112

RESUMO

OBJECTIVE: The aim of this study was to assess the association between serum growth differentiation factor-15(GDF-15) and 3-month depression after acute ischemic stroke. METHODS: In this single-center prospective study, patients with first-ever acute ischemic stroke between March 2017 and November 2018 were included. Neurological and neuropsychological evaluations were conducted during the 3-month follow-up. The predictive value of GDF-15 to predict the post-stroke depression (PSD) within 3 months, was compared with other known predictors. RESULTS: The median level of GDF-15 in 310 stroke patients was 1285(IQR, 846-1934) ng/l. During the 3-month follow-up, 76 patients were defined as depression (24.5%; 95% confidence interval [CI]: 17.9%-29.3%), and GDF-15 levels in those patients were nearly more than 1 time greater as compared with patients who were free of depression (P < 0.001). Using the ROC curves, GDF-15 serum level at 1660 ng/l predicted the PSD with the highest sensitivity and specificity [67.1% and 77.4%, respectively; AUC=0.78, 95%CI: 0.72-0.84; P < 0.001]. Interestingly, When GDF-15 was added to the model containing established significant risk factors, AUROC (standard error) was increased from 0.81(0.029) to 0.88(0.020). A significant difference in the AUC between the established risk factors alone and the addition of GDF-15 was observed (difference, 0.07[0.009]; P = 0.001). In a multivariate model using the elevated levels of GDF-15 (≥cut-off=1660 ng/l) vs. normal (

2.
Langmuir ; 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31789036

RESUMO

Gold-silver(Au@Ag)core-shell nanostructures have stronger surface plasma response, wider absorption and scattering in UV-Vis-NIR region and distictive optical properties, which are widely explored in biosensors, information processing, photothermal therapy, and catalysis. Core-shell nanostructures are usually formed by the deposition of the second metal atoms onto the first core metal particles via chemical wet method. The conventional approaches for the manipulation of the shape usually were done by homogeneous growth or etching of isotropic nanoparticles. Through in situ modification of the first metal core at the different locations, different growth model of the second metal can be regulated to control the shapes of core-shell structures. Herein, We modified the gold nanorods (AuNRs) asymmetrically at the end and side parts using thiolated molecules to regulate the morphology of gold nanorod@silver (AuNR@Ag) core-shell nanoparticles. Interestingly, the obvious eccentric nanostructures of AuNR@Ag core-shell nanoparticles were obtained with the increase of the molecular weight of macromolecules modified at the end of AuNRs. So the growth mode was adjusted from Frank-van der Merwe (F-W) mode to Stranski-Krastanow (S-K) mode. By changing the length of the hydrocarbon chain and functional groups of the small mercaptan molecules at the side of AuNRs, the silver-shell exhibit selectively growth at side of the AuNRs, resulting in heterogeneous core-shell nanoparticles and various shapes of AuNR@Ag core-shell. Our method opens up a new avenue towards preparing core-shell nanostructures with the controlled shapes, and the obtained structures are promising in various applications.

3.
Chin Med J (Engl) ; 132(22): 2657-2663, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31725445

RESUMO

BACKGROUND: Coronary artery disease (CAD) in octogenarians (age of ≥80 years) has a high risk of mortality and high medical expenses. Research shows that the prevalence of CAD is higher among octogenarians than that among younger people, but few such patients undergo percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). This study aimed to evaluate different treatments with respect to their clinical effects and impacts on quality of life of octogenarians with CAD. METHODS: Data of 519 octogenarians with CAD consecutively treated at Beijing Anzhen Hospital, Capital Medical University (Beijing, China) from January 2010 to January 2016 were collected in this study. The patients were categorized into three groups based on the treatments they received: the PCI group (n = 292), CABG group (n = 110), and medical treatment group (n = 117). The followings were recorded during follow-up: clinical data, death (all-cause and cardiovascular-related), re-hospitalization time, Seattle Angina Questionnaire (SAQ) score, and occurrence of hemorrhagic events (cerebral bleeding, gastrointestinal bleeding, and dermal ecchymosis). RESULTS: The median follow-up duration was 25.0 (25th, 75th percentile: 17.0, 55.5) months among 417 patients. The all-cause death rates (28.2% vs. 12.0% and 14.6%, respectively) and cardiovascular-related death rates (15.4% vs. 3.8% and 6.4%, respectively) were significantly higher in the medical treatment group than those in the PCI group and CABG group (all P < 0.05). The re-hospitalization rate for cardiovascular events was significantly lower in the CABG group than those in the PCI group and medical treatment group (3.8% vs. 12.8% and 14.9%, respectively) (χ = 8.238, P = 0.018). The SAQ scores of physical limitation, angina frequency, treatment satisfaction, and disease perception were significantly higher in the PCI group and CABG group than those in the medical treatment group (all P < 0.05). No significant difference in the angina stability score was observed among the three groups (F = 3.179, P = 0.204). CONCLUSION: PCI and CABG result in reduced mortality and better quality of life in octogenarians with CAD.

4.
Adv Mater ; : e1905517, 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31782563

RESUMO

Solid-state lithium-metal batteries with solid electrolytes are promising for next-generation energy-storage devices. However, it remains challenging to develop solid electrolytes that are both mechanically robust and strong against external mechanical load, due to the brittleness of ceramic electrolytes and the softness of polymer electrolytes. Herein, a nacre-inspired design of ceramic/polymer solid composite electrolytes with a "brick-and-mortar" microstructure is proposed. The nacre-like ceramic/polymer electrolyte (NCPE) simultaneously possesses a much higher fracture strain (1.1%) than pure ceramic electrolytes (0.13%) and a much larger ultimate flexural modulus (7.8 GPa) than pure polymer electrolytes (20 MPa). The electrochemical performance of NCPE is also much better than pure ceramic or polymer electrolytes, especially under mechanical load. A 5 × 5 cm2 pouch cell with LAGP/poly(ether-acrylate) NCPE exhibits stable cycling with a capacity retention of 95.6% over 100 cycles at room temperature, even undergoes a large point load of 10 N. In contrast, cells based on pure ceramic and pure polymer electrolyte show poor cycle life. The NCPE provides a new design for solid composite electrolyte and opens up new possibilities for future solid-state lithium-metal batteries and structural energy storage.

5.
HPB (Oxford) ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31732465

RESUMO

BACKGROUND: The aim of this study was to evaluate the effect of portal vein tumor thrombus (PVTT) on the prognosis of patients undergoing liver resection (LR) for primary liver malignancies (PLC). METHODS: The recurrence-free survival (RFS) and overall survival (OS) for patients undergoing LR with and without PVTT for three primary liver malignancies, including hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC) and hepato-cholangio carcinoma (CHC) were compared using the Kaplan-Meier method and Cox regression analysis. RESULTS: In total, 3775 patients with PLC who underwent LR were included in this study. The incidence of PVTT in patients undergoing LR with HCC, IHC and CHC were 46%, 20%, and 17%, respectively. The median RFS and OS were significantly better for patients with HCC as compared to ICC or CHC (16 vs 11 vs 13 months; 21 vs 16 vs 18 months, respectively; P < 0.001). However, the presence of PVTT resulted in similarly poor RFS and OS in these 3 subgroups of patients (9 vs 8 vs 8 months, P = 0.062; 14 vs 13 vs 12 months, respectively, P = 0.052). CONCLUSION: Although the prognosis of patients with PLC varied by histological subtype, once PVTT occurred, survival outcomes after LR were similarly poor across all three subgroups.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31670057

RESUMO

Catecholamines [dopamine (DA), epinephrine (E), and norepinephrine (NE)] and their metabolites [metanephrine (MN), normetanephrine (NMN), and 3-methoxytyramine (3-MT)] are functionally important in humans. Their overexpression can indicate the presence of neuroendocrine tumors. Accurate and rapid quantitation of catecholamines and their metabolites may function in differential diagnosis of neuroendocrine tumors. Herein, we diluted 200 µL plasma using isotope labelled internal standards (IS), and extracted using solid phase extraction. The performance of isotope diluted liquid chromatography tandem mass spectrometry (ID-LC-MS/MS) was evaluated and applied to quantify the level of catecholamines and metabolites in clinical samples from 73 apparently healthy adults. The total analysis time of the ID-LC-MS/MS method was 4 min. The improved method was highly sensitive, with a limit of quantification (LOQ) for MN, NMN, 3-MT, and E of 1 pg/mL, a LOQ for DA of 5 pg/mL, and for NE of 10 pg/mL. After correction using IS, no significant matrix effects were observed. Good reproducibility was obtained, with total CVs of 3.2-13.1% (DA), 4.8-10.0% (E), 6.2-6.9% (NE), 3.8-7.9% (MN), 4.1-8.8% (NMN), 3.4-8.9% (3-MT). Recoveries were in the range of 91.1-109.7% for the six analytes. Also, the mean concentration of catecholamines were as follows: MN, 22.9 ±â€¯7.2 pg/mL; NMN, 41.4 ±â€¯17.2 pg/mL; 3-MT, 2.34 ±â€¯2.01 pg/mL; DA, 10.2 ±â€¯4.6 pg/mL; E, 29.3 ±â€¯14.2 pg/mL and NE 427.0 ±â€¯190.6 pg/mL. A reliable ID-LC-MS/MS method for the determination of catecholamines and their metabolites using small volumes of plasma was verified. This method is rapid, simple, and may serve as an essential diagnostic tool for neuroendocrine tumors in clinical practice.

7.
Langmuir ; 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31697894

RESUMO

Large scaled two-dimensional free-standing monolayer films of gold nanoparticles show distinctive optical, electrical, and chem-physical propertie making them a new class of advanced plasmonic materials differing from bulk materials and individual nanoparticles in solution. The conventional 2D gold nanoparticle films usually possess symmetric structures and identical properties of gold nanoparticles on both sides. Herein, we developed an easy and efficient approach to construct a new type of free-standing 2D gold nanoparticle monolayer film with asymmetric gold nanoparticle structures and functions, called a 2D Janus gold nanoparticle film. The remarkable feature of our method is the subsequent asymmetric growth on one side of the interfacial self-assembled gold nanoparticle monolayer film at the air-liquid interface. It is very easy to control the morphology of the Janus film by simply and precisely adjusting the size and shape of the gold nanoparticles on the top side, and selectively tuning the structure and composition on the bottom side of the film by growing gold nanoparticles or other noble metals such as Ag, Pt, and Pd. Unlike the conventionally prepared Janus films at solid substrate that require long-time etching and transfer procedures, other features of our method include the short time in which the interfacial self-assembly and the subsequent asymmetric growth are completed as well as the easily transferable property of the Janus film onto different substrates, such as quartz glass sheets, silicon wafers, and PDMS. The obtained Janus gold nanoparticle film shows asymmetric wettabilities, optical properties, and surface-enhanced Raman scattering (SERS) effects, which is promising for a range of potential applications in optical devices, sensors, and asymmetric catalysis.

8.
Infection ; 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31677085

RESUMO

BACKGROUND: Inappropriate initial antimicrobial therapy (IIAT) may increase the mortality rate of hematological malignancies (HMs) patients with Gram-negative bacteria bloodstream infections (GN-BSI). The aim of this study is to determine whether IIAT affects the prognosis in this patient population and recommend the appropriate antibiotic regimen to minimize IIAT. METHODS: We reviewed a retrospective cohort study of 361 HM patients with neutropenic fever from GN-BSI. The patients' clinical characteristics and the results of the drug sensitivity test in vitro were analyzed. RESULTS: IIAT rate was 21.3% in HM patients with neutropenic fever caused by GN-BSI. There was a significant difference in 7-day mortality rate between patients treated with appropriate antibiotics and those with IIAT (7.7% vs 29.9%, p < 0.01). Multivariate analysis confirmed that IIAT was an independent risk factors for early mortality [4.860 (1.541-15.323)]. Drug sensitivity data of GN-bacteria suggested that carbapenems monotherapy or beta-lactamase inhibitors (BLBLI) combined with amikacin as the initial therapy can effectively reduce the IIAT rate. In the stratified antibiogram based on prior antimicrobial exposure, our results showed that BLBLI monotherapy could be initially used as an empirical treatment in patients without prior antimicrobial exposure. In those who had received prior antimicrobial exposure, BLBLI (especially piperacillin-tazobactam) combined with amikacin is recommended. CONCLUSIONS: IIAT was a critical factor contributing to the mortality of HM patients with neutropenic fever from GN-BSI.

9.
Clin Chem Lab Med ; 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31655792

RESUMO

Background This study aimed to quantify and compare serum aldosterone (sALD) levels through three different chemiluminescence immunoassays (CLIAs) and liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis. Methods Serum samples from 221 patients with suspected primary aldosteronism (PA) were retrospectively included in this study conducted at the Peking Union Medical College Hospital from June to August in 2017. sALD levels were determined using the LC-MS/MS method and three different CLIA systems, viz., DiaSorin® XL, iSYS and Auto Lumo A2000. Pooled fresh serum samples were used for recalibration. Passing-Bablok regression analysis, correlation matrix, and Bland-Altman plots were used to evaluate the concurrence among ALD levels determined using the three CLIAs. Results Within-laboratory precision of the four assays ranged from 2.1% to 9.4%, except the coefficient variation (CV) of one of the CLIAs, which exceeded 20.0% for samples with low sALD levels. sALD levels determined using LC-MS/MS were significantly lower than those determined using the other three CLIAs (p < 0.0001). Spearman's correlation coefficient of the four assays ranged from 0.745 to 0.950 (p < 0.0001). The Bland-Altman plot showed that the average bias (%) for the three CLIAs and LC-MS/MS ranged from -69.3 to -49.2. After recalibration, this correlation did not improve among the assays. However, the bias and bias percentage at the medical decision level improved between LC-MS/MS and DiaSorin® XL/iSYS. Conclusions Significant inconsistencies between the results of CLIAs and LC-MS/MS indicate that different sALD measures cannot be used interchangeably.

10.
ACS Nano ; 13(10): 11168-11180, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31585038

RESUMO

Elevated hydrogen peroxide (H2O2) in biological tissues is generally recognized to be relevant to the carcinogenesis process that regulates the proliferative activity of cancer cells and the transformation of malignant features. Inspired by this observation, it can be hypothesized that imaging H2O2 in the tumor microenvironment (TME) could help diagnose tumor types and malignancy, and even guide precise therapy. Thus, in this study, a noninvasive photomedicine strategy is demonstrated that leverages the different levels of H2O2 in the TME, and two representative skin cancers, malignant melanoma (MM, clinically higher incidence of metastasis and recurrence) and cutaneous squamous cell carcinoma (cSCC, relatively less dangerous), are differentially diagnosed. The working probe used here is one we previously developed, namely, intelligent H2O2 responsive ABTS-loaded HRP@Gd nanoprobes (iHRANPs). In this study, iHRANPs have advantages over ratiometric imaging due to their bimodal imaging elements, in which the inherent magnetic resonance imaging (MR) mode can be used as the internal imaging reference and the H2O2 responsive photoacoustic (PA) imaging modality can be used for differential diagnosis. Results showed that after intravenous injection of iHRANPs, the tumor signals on both MM and cSCC are obviously enhanced without significant difference under the MR modality. However, under the PA modality, MM and cSCC can be easily distinguished with obvious variations in signal enhancement. Particularly, guided by PA imaging, photothermal therapy (PTT) can be precisely applied on MM, and a strong antitumor effect was achieved owing to the excessive H2O2 in the TME of MM. Furthermore, exogenous H2O2 was injected into cSCC to remedy H2O2 deficiency in the TME of cSCC, and an evident therapeutic efficacy on cSCC can also be realized. This study demonstrated that MM can be differentially diagnosed from cSCC by noninvasive imaging of H2O2 in the TME with iHRANPs; meanwhile, it further enabled imaging-guided precision PTT ablation, even for those unsatisfactory tumor types (cSCC) through exogenously delivering H2O2.

11.
Chem Commun (Camb) ; 55(90): 13506-13509, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31626260
12.
Artigo em Inglês | MEDLINE | ID: mdl-31603775

RESUMO

Fetal congenital heart disease (FHD) is a common and serious congenital malformation in children. In Asia, FHD birth defect rates have reached as high as 9.3‰. For the early detection of birth defects and mortality, echocardiography remains the most effective method for screening fetal heart malformations. However, standard echocardiograms of the fetal heart, especially four-chamber view images, are difficult to obtain. In addition, the pathophysiological changes in fetal hearts during different pregnancy periods lead to ever-changing twodimensional fetal heart structures and hemodynamics, and it requires extensive professional knowledge to recognize and judge disease development. Thus, research on the automatic screening for FHD is necessary. In this paper, we proposed a new model named DGACNN that shows the best performance in recognizing FHD, achieving a rate of 85%. The motivation for this network is to deal with the problem that there are insufficient training datasets to train a robust model. There are many unlabeled video slices, but they are tough and time-consuming to annotate. Thus, how to use these unannotated video slices to improve the DGACNN capability for recognizing FHD, in terms of both recognition accuracy and robustness, is very meaningful for FHD screening. The architecture of DGACNN comprises two parts, that is, DANomaly and GACNN (Wgan-GP and CNN). DANomaly, similar to the ALOCC network, but incorporates cycle adversarial learning to train an end-to-end one-class classification (OCC) network that is more robust and has a higher accuracy than ALOCC in screening video slices. For the GACNN architecture, we use FCH(four chamber heart) video slices at around the endsystole, as screened by DANomaly, to train a WGAN-GP for the purpose of obtaining ideal low-level features that can robustly improve the FHD recognition accuracy. A few annotated video slices, as screened by DANomaly, can also be used for data augmentation so as to improve the FHD recognition further. The experiments show that the DGACNN outperforms other state-of-the-art networks by 1%-20% in recognizing FHD.A comparison experiment shows that the proposed network already outperforms the performance of expert cardiologists in recognizing FHD, reaching 84% in a test. Thus, the proposed architecture has high potential for helping cardiologists complete early FHD screenings.

13.
Opt Lett ; 44(20): 5081-5084, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31613269

RESUMO

We propose and experimentally demonstrate an apodized bidirectional grating coupler for high-efficiency, perfectly vertical coupling. Through grating apodization, the coupling efficiency (CE) can be notably improved, and the parasitic reflections can be minimized. For ease of fabrication, subwavelength gratings are introduced, which are also beneficial for the coupling performance. Simulation shows a record CE of 72%. We found that the coupler is quite robust to the variation of incidence mode field diameter and fiber misalignment. A CE of -1.8 dB is experimentally measured with a 1-dB bandwidth of 37 nm.

15.
Biomaterials ; 224: 119500, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31557591

RESUMO

Redox homeostasis inside malignant cells is a defense mechanism against the reactive oxygen species (ROS)-induced therapy means, but little importance has been paid to this innate barrier. The present study intends to make cancer cells more sensitive to the ROS-induced therapy by disturbing cellular redox homeostasis. To verify this concept, a porous metal-organic framework (MOF) serves not only as the photodynamic therapy (PDT) agent but also as the carrier to transport alkaloid piperlongumine (PL), a thioredoxin reductase (TrxR) inhibitor used to disturb cellular redox homeostasis. The PL-loaded MOF was further coated with cancer cell membranes to gain homologous tumor-targeting capability. Inside tumor cells, the released PL can effectively block the TrxR-mediated ROS elimination pathway. The resultant data show that compared to traditional PDT alone, the combination of PDT and TrxR inhibition causes profound promotions in cellular ROS level by about 1.6 times, in cytotoxicity by about 2 times, and in cellular apoptosis/necrosis rate by about 3 times. Consequently, this strategy based on the interference with cellular redox homeostasis has demonstrated high potency to improve the anticancer PDT performance, adumbrating a new way to boost the power of ROS-induced therapy.

16.
Dalton Trans ; 48(40): 15105-15113, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31559974

RESUMO

Pt(ii) complexes that exhibit long-lived triplet excited state lifetimes are promising for optical power limiting materials. The introduction of large π-conjugated substituents can switch the triplet excited state to a long-lived 3π,π* state. Herein, we report four Pt(ii) diimine complexes with high π-conjugation via inserting an aryl group on the diimine ligand. Their photophysical properties were investigated using spectroscopic techniques. All the complexes exhibit strong ground absorption bands in their UV-Vis absorption spectra (maximum peaks ranging from 370 to 530 nm) and long-lived emission and triplet excited states. The insertion of π-conjugated substituents induces a pronounced red-shift in the ground state absorption and longer emission lifetime. Broadband transient absorption spectra in the visible-NIR region and Z-scan properties under 532 nm were carried out on the Pt(ii) diimine complexes, resulting in a remarkably strong reverse saturable absorption at 532 nm for nanosecond laser pulses. Otherwise, the high π-conjugation in the bipyridyl ligand increases the reverse saturable absorption. Therefore, these Pt(ii) diimine complexes with high π-conjugation are excellent candidates for devices that require strong reverse saturable absorption.

17.
Aging (Albany NY) ; 11(16): 6385-6397, 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31454331

RESUMO

Hemorrhagic transformation (HT) is a severe complication occurring in acute ischemic stroke (AIS) patients. We explored the association between low triiodothyronine (T3) syndrome and HT in AIS patients. A total of 208 consecutive participants with HT and 208 age- and sex-matched stroke patients without HT were enrolled in this study. HT was diagnosed by follow-up imaging assessment, and was radiologically classified as hemorrhagic infarction (HI) type 1 or 2 or parenchymal hematoma (PH) type 1 or 2. HT was also classified into asymptomatic or symptomatic. The incidence of low T3 syndrome was significantly higher among patients who developed HT than among those without HT. Moreover, the more severe the HT, the lower the detected T3 levels. Multivariate-adjusted binary logistic regression showed that low T3 syndrome was an independent risk factor for HT and symptomatic HT in AIS patients. Low T3 syndrome was also significantly associated with a higher risk of PH, but not with the risk of HI. Thus, low T3 syndrome was independently associated with the risk of HT, symptomatic HT, and severe HT (PH) in AIS patients, which suggests monitoring T3 could be a useful means of preventing HT in patients with ischemic stroke.

18.
J Exp Clin Cancer Res ; 38(1): 362, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31426831

RESUMO

BACKGROUND: Tumor targeting small molecular inhibitors are the most popular treatments for many malignant diseases, including cancer. However, the lower clinical response and drug resistance still limit their clinical efficacies. HGFK1, the first kringle domain of hepatocyte growth factor, has been defined as a potent anti-angiogenic factor. Here, we aimed to develop and identify novel nanoparticles-PH1/pHGFK1 as potential therapeutic agents for the treatment of renal cell carcinoma (RCC). METHODS: We produced a novel cationic polymer-PH1 and investigated the anti-tumor activity of PH1/pHGFK1 nanoparticle alone and its combination therapy with sorafenib in RCC cell line xenografted mice model. Then, we figured out its molecular mechanisms in human RCC cell lines in vitro. RESULTS: We firstly demonstrated that intravenous injection of PH1/pHGFK1 nanoparticles significantly inhibited tumor growth and prolonged the survival time of tumor-bearing mice, as well as synergistically enhanced anti-tumor activities of sorafenib. Furthermore, we elucidated that recombinant HGFK1 improved sorafenib-induced cell apoptosis and arrested cell cycle. In addition, HGFK1 could also decrease sorafenib-induced autophagy and stemness via blockading NF-κB signaling pathway in RCC both in vitro and in vivo. CONCLUSIONS: HGFK1 could inhibit tumor growth, synergistically enhance anti-tumor activities of sorafenib and reverse its drug resistance evolution in RCC. Our results provide rational basis for clinical application of sorafenib and HGFK1 combination therapy in RCC patients.

20.
Kidney Int ; 96(5): 1105-1120, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31405732

RESUMO

Inflammation and tubular cell death are the hallmarks of acute kidney injury. However, the precise mechanism underlying these effects has not been fully elucidated. Here we tested whether caspase-11, an inflammatory member of the caspase family, was increased in cisplatin or ischemia-reperfusion-induced acute kidney injury. Caspase-11 knockout mice after cisplatin treatment exhibited attenuated deterioration of renal functional, reduced tubular damage, reduced macrophage and neutrophil infiltration, and decreased urinary IL-18 excretion. Mechanistically, the upregulation of caspase-11 by either cisplatin or ischemia-reperfusion cleaved gasdermin D (GSDMD) into GSDMD-N, which translocated onto the plasma membrane, thus triggering cell pyroptosis and facilitated IL-18 release in primary cultured renal tubular cells. These results were further confirmed in GSDMD knockout mice that cisplatin-induced renal morphological and functional deterioration as well as urinary IL-18 excretion were alleviated. Furthermore, deficiency of GSDMD significantly suppressed cisplatin-induced IL-18 release but not the transcription and maturation level of IL-18 in tubular cells. Thus, our study indicates that caspase-11/GSDMD dependent tubule cell pyroptosis plays a significant role in initiating tubular cell damage, urinary IL-18 excretion and renal functional deterioration in acute kidney injury.

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