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1.
Pediatr Hematol Oncol ; : 1-9, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33792506

RESUMO

This study reports a case of superficial CD34-positive fibroblastic tumor (SCPFT) in a child and analyze the major known clinicopathological features of SCPFT and other skin mesenchymal tumors, contributing to an accurate diagnosis of this rare disease. We summarize the clinicopathologic features of an 8-year-old girl who was diagnosed with SCPFT and 46 previously reported SCPFT cases. Post-operative histopathologic examination of the current case showed the tumor lesion was well-circumscribed; tumor cells were spindled-to-polygonal with a fascicular pattern; most nuclei displayed hyperchromasia and low mitotic rate; intranuclear pseudoinclusions could be found; and abundant eosinophilic cytoplasm and partial myxoid stroma were observed. Immunohistochemistry revealed strong and diffuse CD34-positivity, vimentin staining positively but no S-100, SMA, NSE, CD31, desmin, cytokeratin, STAT6, ß-catenin, MDM2, or ERG expression. The Ki-67 and CD68 labeling indexes were approximately 1%. There were no rearrangements of PDGFB or PRDM10 tested by FISH. After surgical resection, the patient had no signs of recurrence or metastasis at a 6-month follow-up. The present case is the first that describes SCPFT in children and has significant clinical implications. SCPFT should be differentiated from other skin mesenchymal tumors. The presented compilation of all so far published SCPFT cases will help in diagnosing successfully SCPFT and increasing awareness of this tumor to guide clinical practice.

2.
Neural Regen Res ; 16(11): 2276-2283, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33818513

RESUMO

Axon regeneration and remyelination of the damaged region is the most common repair strategy for spinal cord injury. However, achieving good outcome remains difficult. Our previous study showed that porcine decellularized optic nerve better mimics the extracellular matrix of the embryonic porcine optic nerve and promotes the directional growth of dorsal root ganglion neurites. However, it has not been reported whether this material promotes axonal regeneration in vivo. In the present study, a porcine decellularized optic nerve was seeded with neurotrophin-3-overexpressing Schwann cells. This functional scaffold promoted the directional growth and remyelination of regenerating axons. In vitro, the porcine decellularized optic nerve contained many straight, longitudinal channels with a uniform distribution, and microscopic pores were present in the channel wall. The spatial micro topological structure and extracellular matrix were conducive to the adhesion, survival and migration of neural stem cells. The scaffold promoted the directional growth of dorsal root ganglion neurites, and showed strong potential for myelin regeneration. Furthermore, we transplanted the porcine decellularized optic nerve containing neurotrophin-3-overexpressing Schwann cells in a rat model of T10 spinal cord defect in vivo. Four weeks later, the regenerating axons grew straight, the myelin sheath in the injured/transplanted area recovered its structure, and simultaneously, the number of inflammatory cells and the expression of chondroitin sulfate proteoglycans were reduced. Together, these findings suggest that porcine decellularized optic nerve loaded with Schwann cells overexpressing neurotrophin-3 promotes the directional growth of regenerating spinal cord axons as well as myelin regeneration. All procedures involving animals were conducted in accordance with the ethical standards of the Institutional Animal Care and Use Committee of Sun Yat-sen University (approval No. SYSU-IACUC-2019-B034) on February 28, 2019.

3.
Sensors (Basel) ; 21(6)2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33809743

RESUMO

State estimation is widely used in various automated systems, including IoT systems, unmanned systems, robots, etc. In traditional state estimation, measurement data are instantaneous and processed in real time. With modern systems' development, sensors can obtain more and more signals and store them. Therefore, how to use these measurement big data to improve the performance of state estimation has become a hot research issue in this field. This paper reviews the development of state estimation and future development trends. First, we review the model-based state estimation methods, including the Kalman filter, such as the extended Kalman filter (EKF), unscented Kalman filter (UKF), cubature Kalman filter (CKF), etc. Particle filters and Gaussian mixture filters that can handle mixed Gaussian noise are discussed, too. These methods have high requirements for models, while it is not easy to obtain accurate system models in practice. The emergence of robust filters, the interacting multiple model (IMM), and adaptive filters are also mentioned here. Secondly, the current research status of data-driven state estimation methods is introduced based on network learning. Finally, the main research results for hybrid filters obtained in recent years are summarized and discussed, which combine model-based methods and data-driven methods. This paper is based on state estimation research results and provides a more detailed overview of model-driven, data-driven, and hybrid-driven approaches. The main algorithm of each method is provided so that beginners can have a clearer understanding. Additionally, it discusses the future development trends for researchers in state estimation.

4.
Exp Cell Res ; 402(2): 112574, 2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33794264

RESUMO

Congenital anorectal malformations (ARMs) are among the most prominent deformities of the gastrointestinal tract; however, their precise aetiology remains obscure. Immunohistochemistry demonstrated that, in the ARM group, the PPPDE1-positive cells were widely distributed in the hindgut epithelial tissue from GD13 to GD16. Immunofluorescence revealed that most TUNEL-, Bax-, and Cytochrome C (Cyt C)-positive cells overlapped with PPPDE1-positive cells in the urorectal septum (URS). Western blotting and quantitative real-time RT-PCR revealed that PPPDE1 levels were significantly higher in the ARM group from GD13 to GD14 (p < 0.05). IEC-6 cells were transfected with PPPDE1 overexpression plasmid/NC (negative control) or si-PPPDE1/si-NC. Flow cytometry analysis and CCK-8 assay (used to detect apoptosis and proliferation, respectively), as well as western blotting, showed that the levels of PPPDE1 were positively correlated with the pro-apoptotic molecules Bax and Cyt C. Accordingly, aberrantly high expression of PPPDE1 caused a spatiotemporal imbalance in foetal rats with ARMs during hindgut development. Therefore, the upregulation of PPPDE1 may promote epithelial apoptosis and reduce proliferation in the hindgut via the mitochondrial apoptotic pathway. This could affect the fusion of the URS and cloacal membrane, ultimately inhibiting the hindgut development and resulting in ARMs.

5.
Zhongguo Zhong Yao Za Zhi ; 46(5): 1017-1025, 2021 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-33787092

RESUMO

Schisandrae has a long history of medicinal use in China. Domestic and foreign scholars have isolated a variety of chemical constituents from Schisandrae Sphenantherae Fructus and Schisandrae Chinensis Fructus, including lignans, volatile oils, polysaccharides, triterpenoids, organic acids, amino acids and so on. Pharmacological studies have shown that their alcohol extracts, water extracts, lignan monomers and polysaccharides could protect liver injury and reduce enzyme ability by a variety of hepatoprotective effects such as enzyme reducing, liver protecting, and antioxidant effect. In this paper, the researches on the chemical composition, hepatoprotective effect and pharmacokinetics of Schisandrae Sphenantherae Fructus and Schisandrae Chinensis Fructus in the past forty years were systematically collated, in order to provide useful enlightenment for the clinical application and new drug development of Schisandrae Sphenantherae Fructus and Schisandrae Chinensis Fructus in liver protection.


Assuntos
Medicamentos de Ervas Chinesas , Lignanas , Schisandra , China , Frutas , Lignanas/farmacologia
6.
J Pharm Pharmacol ; 2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33779714

RESUMO

OBJECTIVES: The aim of this study was to evaluate the effects of fasudil on insulin resistance (IR) in HTR-8/SVneo cells. METHODS: HTR-8/SVneo cells were treated with insulin or/and fasudil. Cell proliferation, apoptosis, inflammation and related signalling pathways were assessed. KEY FINDINGS: Insulin treatment significantly enhanced the protein expressions of RhoA and Rho kinase (ROCK1 and ROCK2), but decreased glucose consumption. Administration of fasudil effectively promoted glucose uptake. Moreover, fasudil enhanced cell viability and the level of proliferating cell nuclear antigen (PCNA). Insulin-mediated cell apoptosis was inhibited by fasudil via the down-regulation of bax and cleaved-caspase-3, and the up-regulation of bcl-2. At the same time, fasudil led to the reduction of IL-1ß, TNF-α, IL-6 and IL-8 mRNA levels in insulin-treated cells. In addition, RhoA, ROCK2 and phosphorylated myosin phosphatase target subunit-1 (p-MYPT-1) expressions were down-regulated by fasudil. Importantly, fasudil activated insulin receptor substrate-1 (IRS-1) through increasing p-IRS-1 (Tyr612) and p-Akt expressions. The nuclear NF-κB p65 and p-IκB-α levels were reduced via the administration of fasudil in insulin-treated cells. CONCLUSIONS: Fasudil mitigated IR by the promotion of cell proliferation, inhibition of apoptosis and inflammation and regulation of RhoA/ROCK/insulin/NF-κB signalling pathway through in vitro studies.

7.
Sci Rep ; 11(1): 6694, 2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33758217

RESUMO

Picea mongolica, a native species with excellent industrial wood quality and strong sand-fixing capacity, may be utilized in construction of urban green spaces in arid areas in China. However, now the sustainability of the ecosystems where this species grows is at serious risk due to a lack of natural regeneration. In this study, we developed an efficient regeneration system and comprehensively analyzed various factors affecting somatic embryogenesis (SE) using zygotic embryos as explants. We identified the optimal plant growth regulators (PGRs) performance and the best donor trees (k81) for the generation of somatic embryos (SEMs). Additionally, we confirmed that the positive developmental window of SEMs initiation was at the end of July to early August, which is when zygotic embryos was at the late embryogeny. In this time period, specific transcripts associated with the regulation of epigenetic modifications, plant hormone-related genes, and embryonic development-related transcription factors play important roles for early SEMs initiation. These results may provide a valuable resource for vegetative propagation of Picea mongolica. Our results may help to establish a reliable protocol for plantlet regeneration, which may facilitate urban greening applications and industrialization in arid areas.

8.
Biol Trace Elem Res ; 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33768429

RESUMO

The aim of our study was to observe the effect of selenium (Se) deficiency on inflammatory injury in the bursa of Fabricius of broiler chickens and to determine the role of the Toll-like receptor (TLR)/myeloid differential protein-88 (MyD88)/nuclear factor-κB (NF-κB) signaling pathway during this process. Here, we revealed that severe inflammatory injury occurred in the broiler bursa of Fabricius with Se deficiency via histopathology. Moreover, the ultrastructural pathological results showed that the nuclear, mitochondrial, endoplasmic reticulum and cytomembrane structures were damaged to varying degrees. Additionally, interleukin-2 (IL-2), interleukin-6 (IL-6), and interferon (IFN-γ) mRNA expression was markedly upregulated in the broiler bursa of Fabricius with Se deficiency. Furthermore, TLR, toll-interleukin-1 receptor domain-containing adapter-inducing interferon-ß (TRIF), MyD88, and NF-κB mRNA expression was also markedly elevated in the broiler bursa of Fabricius with Se deficiency. The above results suggested that Se deficiency increases the expression of numerous proinflammatory cytokines and is probably due to the activation of the TLR/MyD88/NF-κB signaling pathway, which causes inflammatory injury in the bursa of Fabricius of broiler chickens. Our findings provide a theoretical reference for further studying the underlying mechanism of Se deficiency-induced inflammatory injury in the bursa of Fabricius of broiler chickens.

9.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(3): 294-299, 2021 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-33691925

RESUMO

OBJECTIVE: To study the role and mechanism of histone deacetylase 1 (HDAC1) and histone deacetylase 2 (HDAC2) in mouse neuronal development. METHODS: The mice with Synapsin1-Cre recombinase were bred with HDAC1&2flox/flox mice to obtain the mice with neuron-specific HDAC1&2 conditional knockout (knockout group), and their littermates without HDAC1&2 knockout were used as the control group. The general status of the mice was observed and survival curves were plotted. Brain tissue samples were collected from the knockout group and the control group. Western blot and immunohistochemistry were used to measure the protein expression of related neuronal and axonal markers, neuronal nuclear antigen (NeuN), non-phosphorylated neurofilament heavy chain (np-NF200), and phosphorylated neurofilament heavy chain (p-NF200), as well as the downstream effector of the mTOR signaling pathway, phosphorylated S6 ribosomal protein (p-S6). RESULTS: The mice with HDAC1&2 conditional knockout usually died within one month after birth and were significantly smaller than those in the control group, with motor function abnormalities such as tremor and clasping of hindlimbs. Compared with the control group, the knockout group had significant reductions in the protein expression levels of NeuN, np-NF200, p-NF200, and p-S6 (P < 0.05; n=3). CONCLUSIONS: Deletion of HDAC1 and HDAC2 in mouse neurons results in reduced neuronal maturation and axonal dysplasia, which may be associated with the mTOR signaling pathway.


Assuntos
Histona Desacetilase 2 , Histona Desacetilases , Animais , Western Blotting , Histona Desacetilase 1/genética , Histona Desacetilases/genética , Imuno-Histoquímica , Camundongos , Neurônios/metabolismo , Transdução de Sinais
10.
Int J Med Sci ; 18(7): 1618-1627, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33746578

RESUMO

Hypoxia affects proliferation, differentiation, as well as death of cardiomyocyte, and plays an important role in the development of myocardial ischemia. However, the detailed mechanisms through which hypoxia regulates cardiomyocyte ferroptosis have not been explored. In this study, we revealed that hypoxia suppresses the proliferation, migration, and erastin-induced ferroptosis of H9c2 cells. First, we confirmed the upregulation of SENP1 in H9c2 cells cultured under hypoxic conditions. Through adenovirus-mediated SENP1 gene transfection, we demonstrated that SENP1 overexpression could enhance H9c2 cell proliferation and migration while also protecting H9c2 cells from erastin-induced ferroptosis. Furthermore, through immunoprecipitation and western blotting, we confirmed that SENP1 mediated deSUMOylation of HIF-1α and ACSL4 in H9c2 cells. In conclusion, this study describes the underlying mechanism through which hypoxia upregulates SENP1 expression, in turn protecting against ferroptosis via the regulation of HIF-1α and ACSL4 deSUMOylation. Our findings provide a theoretical foundation for the development of novel therapeutics for ischemic heart diseases.

11.
Infect Immun ; 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33722928

RESUMO

H9N2 avian influenza virus has been continuously circulating among poultry and could infect mammals, indicating that this virus is a potential pandemic strain. During influenza pandemics, secondary bacterial (particularly pneumococcal) pneumonia usually contributes to excess mortality. In the present study, we observed the dynamic effect of H9N2 virus infection on host defense against secondary pneumococcal infection in mice. BALB/c mice were intranasally inoculated with 1.2 × 105 plaque forming units (PFU) of H9N2 virus followed by 1 × 106 colony forming units of Streptococcus pneumoniae on 7, 14 or 28 days post-H9N2 infection (D.P.I.). The bacterial load, histopathology, body weight and survival were assessed after pneumococcal infection. Our results showed that H9N2 virus infection had no significant impact on host resistance to secondary pneumococcal infection on 7 D.P.I. However, H9N2 virus infection increased pulmonary pneumococcal clearance and reduced pneumococcal pneumonia-induced morbidity after secondary pneumococcal infection on 14 or 28 D.P.I., as reflected by significantly decreased bacterial loads, markedly alleviated pulmonary histopathological changes and significantly reduced weight loss in mice infected with H9N2 virus followed by S. pneumoniae compared with mice infected only with S. pneumoniae Further, the significantly decreased bacterial loads were observed when mice were previously infected with a higher dose (1.2 × 106 PFU) of H9N2 virus. Besides, similar to the results obtained in BALB/c mice, improvement in pulmonary pneumococcal clearance was also observed in C57BL/6 mice. Overall, our results showed that pulmonary pneumococcal clearance is improved after resolution of H9N2 virus infection in mice.

12.
Entropy (Basel) ; 23(2)2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33670098

RESUMO

Trend prediction based on sensor data in a multi-sensor system is an important topic. As the number of sensors increases, we can measure and store more and more data. However, the increase in data has not effectively improved prediction performance. This paper focuses on this problem and presents a distributed predictor that can overcome unrelated data and sensor noise: First, we define the causality entropy to calculate the measurement's causality. Then, the series causality coefficient (SCC) is proposed to select the high causal measurement as the input data. To overcome the traditional deep learning network's over-fitting to the sensor noise, the Bayesian method is used to obtain the weight distribution characteristics of the sub-predictor network. A multi-layer perceptron (MLP) is constructed as the fusion layer to fuse the results from different sub-predictors. The experiments were implemented to verify the effectiveness of the proposed method by meteorological data from Beijing. The results show that the proposed predictor can effectively model the multi-sensor system's big measurement data to improve prediction performance.

13.
Biol Trace Elem Res ; 2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33704669

RESUMO

Cadmium (Cd) is a harmful heavy metal pollutant, which can cause oxidative stress in the body and induce cell damage. Reactive oxygen species (ROS) is a general term for substances that contain oxygen and are active in the body. However, excessive ROS can damage the body. Cadmium poisoning can cause a large amount of ROS in cells and autophagy. Astragalus polysaccharide (APS) is a plant polysaccharide with biological functions, such as antioxidant and anti-stress activities. In this study, chicken embryo fibroblasts (CEF) were used to determine the relationship between ROS and autophagy damage of Cd-infected cells and the mechanism of APS on cadmium-induced autophagy damage. The results showed that a 10-µL dose of 10 µmol/L cadmium chloride (CdCl2) can induce CEF autophagy and damage when CEF was added for 36 h. Cadmium induced CEF autophagy damage by increasing ROS production. APS could significantly reduce ROS production and LC3-II and Beclin-1 protein expression, increase the expression of mTOR and the level of antioxidation, and restore the viability and morphological damage of CEF exposed to Cd. Our study suggests that APS can alleviate Cd-induced CEF autophagy damage by reducing the production of ROS.

14.
Artigo em Inglês | MEDLINE | ID: mdl-33721163

RESUMO

Ice cover is a common channel phenomenon in some cold regions. But most of the researchers focused on the velocity distribution; the suspended sediment and phosphorus distribution in an ice-covered channel need more attention. Six different discharge treatments were carried out in this paper; and vertical velocity, suspended sediment, and phosphorus concentration were measured. The results showed, based on the convection-diffusion equation of sediment, the analytical solution of sediment vertical distribution given, and the coefficient of determination (R2) between the measured data and predicted data ranging from 0.9519 to 0.9777 and the root mean square error (RMSE) between the measured data and predicted data ranging from 0.2959 to 0.5892, that the analytical solution has a good simulation result. Particulate phosphorus concentration (Cp) is smaller in the top layer and larger in the bottom layer, and the dissolved phosphorus concentration (Cd) is larger in the middle and small in both sides; partition coefficient (Kd) is uniform in the channel which is assumed as a constant in previous studies. This result is helpful to know the retention law of suspended sediment and phosphorus in an ice-covered channel.

15.
Sci Rep ; 11(1): 5907, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33723331

RESUMO

The functional significance of extracellular Niemann-Pick disease type C2 protein (NPC2) is poorly defined. It is not known whether there is an association between plasma NPC2 and sepsis. Our exploratory, quantitative proteomic analysis showed a significant increase in the level of plasma NPC2 in moribund sepsis patients. Thus, we subsequently determined NPC2 concentration in plasma from healthy subjects, pneumonia patients and sepsis patients with comorbid pneumonia; and analyzed the association of plasma NPC2 with organ dysfunction and prognosis of sepsis patients. Our data shows that plasma NPC2 concentration was significantly higher in pneumonia and sepsis patients than healthy subjects, and was further increased in sepsis patients when the SOFA score reached 14. In addition, NPC2 concentration was significantly higher in patients that subsequently developed septic shock or died within 30 days. Moreover, NPC2 level showed the strongest association with the degree of renal dysfunction in sepsis patients. In moribund sepsis patients, however, NPC2 had highest correlation coefficient with indicators of coagulation anomaly. Based on these results, we conclude that the increase in plasma NPC2 in sepsis patients is associated with multiple organ failure, possibly results from a deficiency in renal clearance, and may serve as a prognostic marker for sepsis.

16.
Biomed Environ Sci ; 34(1): 40-49, 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33531106

RESUMO

Objective: Epidemiological studies reveal that exposure to fine particulate matter (aerodynamic diameter ≤ 2.5 µm, PM 2.5) increases the morbidity and mortality of respiratory diseases. Emerging evidence suggests that human circulating extracellular vesicles (EVs) may offer protective effects against injury caused by particulate matter. Currently, however, whether EVs attenuate PM 2.5-induced A549 cell apoptosis is unknown. Methods: EVs were isolated from the serum of healthy subjects, quantified via nanoparticle tracking analysis, and qualified by the marker protein CD63. PM 2.5-exposed (50 µg/mL) A549 cells were pre-treated with 10 µg/mL EVs for 24 h. Cell viability, cell apoptosis, and AKT activation were assessed via Cell Counting Kit-8, flow cytometry, and Western blot, respectively. A rescue experiment was also performed using MK2206, an AKT inhibitor. Results: PM 2.5 exposure caused a 100% increase in cell apoptosis. EVs treatment reduced cell apoptosis by 10%, promoted cell survival, and inhibited the PM 2.5-induced upregulation of Bax/Bcl2 and cleaved caspase 3/caspase 3 in PM 2.5-exposed A549 cells. Moreover, EVs treatment reversed PM 2.5-induced reductions in p-AKT Thr308 and p-AKT Ser473. AKT inhibition attenuated the anti-apoptotic effect of EVs treatment on PM 2.5-exposed A549 cells. Conclusions: EVs treatment promotes cell survival and attenuates PM 2.5-induced cell apoptosis via AKT phosphorylation. Human serum-derived EVs may be an efficacious novel therapeutic strategy in PM 2.5-induced lung injury.


Assuntos
Poluentes Atmosféricos/toxicidade , Vesículas Extracelulares , Material Particulado/toxicidade , Substâncias Protetoras/farmacologia , Soro , Células A549 , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-akt/metabolismo
18.
J Zhejiang Univ Sci B ; 22(2): 87-98, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33615750

RESUMO

The emergence of coronavirus disease 2019 (COVID-19) not only poses a serious threat to the health of people worldwide but also affects the global economy. The outbreak of COVID-19 began in December 2019, at the same time as the influenza season. However, as the treatments and prognoses of COVID-19 and influenza are different, it is important to accurately differentiate these two different respiratory tract infections on the basis of their respective early-stage characteristics. We reviewed official documents and news released by the National Health Commission of the People's Republic of China, the Chinese Center for Disease Control and Prevention (China CDC), the United States CDC, and the World Health Organization (WHO), and we also searched the PubMed, Web of Science, Excerpta Medica database (Embase), China National Knowledge Infrastructure (CNKI), Wanfang, preprinted bioRxiv and medRxiv databases for documents and guidelines from earliest available date up until October 3rd, 2020. We obtained the latest information about COVID-19 and influenza and summarized and compared their biological characteristics, epidemiology, clinical manifestations, pathological mechanisms, treatments, and prognostic factors. We show that although COVID-19 and influenza are different in many ways, there are numerous similarities; thus, in addition to using nucleic acid-based polymerase chain reaction (PCR) and antibody-based approaches, clinicians and epidemiologists should distinguish between the two using their respective characteristics in early stages. We should utilize experiences from other epidemics to provide additional guidance for the treatment and prevention of COVID-19.


Assuntos
Influenza Humana , Pandemias , /diagnóstico , /terapia , Diagnóstico Diferencial , Feminino , Humanos , Influenza Humana/diagnóstico , Influenza Humana/prevenção & controle , Influenza Humana/terapia , Masculino , Pandemias/prevenção & controle , Prognóstico
19.
Oral Oncol ; 115: 105222, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33610004

RESUMO

BACKGROUND: There is no standard-of-care for recurrent, metastatic nasopharyngeal carcinoma (rmNPC) after first-line chemotherapy. Here, we report the efficacy and safety data of apatinib in rmNPC patients. METHODS: Thirty-five biopsy-proven rmNPC patients received apatinib at 500 mg/day under a compassionate access programme. Primary end-point was objective response rate (ORR; RECIST v1.1). Kaplan-meier method was used to estimate progression-free survival (PFS) and overall survival (OS). Toxicity was assessed by CTCAE v4.0. RESULTS: 82.9% (29 of 35) of patients had poly-metastatic rmNPC. All patients, except five, were platinum-refractory; 37.1% (13 of 35) received ≥ 2 lines. Median number of apatinib cycles was 4.0 (IQR: 2.0-8.0). ORR was 31.4% (11 of 35 [95% CI: 16.9-49.3]) and disease control rate was 74.3% (26 of 35 [95% CI: 56.7-87.5]); 11 (31.4%) and 4 (11.4%) patients demonstrated response for ≥ 6 and ≥ 12 months, respectively. Median PFS and OS was 3.9 (95% CI: 3.1-5.5) months and 5.8 (95% CI: 4.5-8.0) months, respectively. Among the ≥ 12-month responders, all patients had pre-apatinib EBV DNA titer of <700 (range: 353-622) copies/ml; this was consistent with the association of PFS with pre-apatinib EBV DNA titer (adjusted HR 3.364 [95% CI: 1.428-7.923] for ≥ 4000 copies/ml, P = 0.006). 42.9% (15 of 35) of patients required dose reduction. Nonetheless, only five (14.3%) patients suffered from G3 toxicities (two haematological, one hypertension, one hand-foot syndrome and one elevated aminotransferases). CONCLUSION: Our data suggests potential efficacy of apatinib in rmNPC patients. Although incidence of severe toxicities was low, dose modification was required in 42.9% of patients.

20.
Toxicology ; 451: 152685, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33486070

RESUMO

Hydrogen sulfide (H2S) as the third gasotransmitter molecule serves various biological regulatory roles in health and disease. Acrylonitrile (AN) is a common occupational toxicant and environmental pollutant, causing brain and liver damage in mammals. The biotransformation of AN is dependent-upon reduced glutathione (GSH), cysteine and other sulfur-containing compounds. However, the effects of AN on the endogenous H2S biosynthesis pathway have yet to be determined. Herein, we demonstrated that a single exposure to AN (at 25, 50, or 75 mg/kg for 1, 6 or 24 h) decreased the endogenous H2S content and H2S-producing capacity in a dose-dependent manner, both in the cerebral cortex and liver of rats in vivo. In addition, the inhibitory effects of AN (1, 2.5, 5, 10 mM for 12 h) on the H2S content and/or the expression of H2S-producing enzymes were also found both in primary rat astrocytes and rat liver cell line (BRL cells). Impairment in the H2S biosynthesis pathway was also assessed in primary rat astrocytes treated with AN. It was found that inhibition of the cystathionine-ß-synthase (CBS)/3-mercaptopyruvate sulfurtransferase (3-MPST)-H2S pathway with the CBS inhibitor or 3-MPST-targeted siRNA significantly increased the AN-induced (5 mM for 12 h) cytotoxicity in astrocytes. In turn, CBS activation or 3-MPST overexpression as well as exogenous NaHS supplementation significantly attenuated AN-induced cytotoxicity. Taken together, endogenous H2S biosynthesis pathway was disrupted in rats acutely exposed to AN, which contributes to acute AN neurotoxicity in primary rat astrocytes.

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