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1.
Int J Mol Sci ; 21(19)2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33036484

RESUMO

The phenotypic switch of vascular smooth muscle cells (VSMCs) plays a pivotal role in the development of vascular disorders, such as atherosclerosis, stenosis and restenosis, after vascular intervention. In our previous study, n-butylidenephthalide (BP) was reported to have anti-proliferating and apoptotic effects on VSMCs. The purpose of the current study is to further investigate its role in platelet-derived growth factor (PDGF)-induced VSMC phenotypic modulation in an arteriovenous fistula model. In vitro, we observed that BP inhibited the PDGF-induced cytoskeleton reorganization of the VSMCs. The enhanced expression of vimentin and collagen, as well as the migration ability induced by PDGF, were also inhibited by BP. By cell cycle analysis, we found that BP inhibited the PDGF-induced VSMCs proliferation and arrested the VSMCs in the G0/G1 phase. In an arteriovenous fistula rat model, the formation of stenosis, which was coupled with a thrombus, and the expression of vimentin and collagen in VSMCs, were also inhibited by administration of BP, indicating that BP inhibited the PDGF-induced phenotypic switch and the migration of VSMCs. Besides, the inhibitory effects of BP on the phenotypic switch were found to accompany the activated 5' AMP-activated protein kinase (AMPK) as well as the inhibited phosphorylation of mTOR. Knockdown of AMPK by gene silencing conflicted the effects of BP and further exacerbated the PDGF-induced VSMCs phenotypic switch, confirming the modulating effect that BP exerted on the VSMCs by this pathway. These findings suggest that BP may contribute to the vasculoprotective potential in vasculature.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33041225

RESUMO

BACKGROUND: Despite the increasing incidence rate of colorectal neuroendocrine carcinoma (CR-NEC), there are still few sequencing data to depict the genomic characteristics of CR-NEC. PATIENTS AND METHODS: Next-generation sequencing data of CR-NEC, colorectal adenocarcinoma (COREAD), lung neuroendocrine carcinoma (lung NEC), and gastrointestinal neuroendocrine tumor (GI-NET) were retrieved from the American Association of Cancer Research Project Genomics, Evidence, Neoplasia, Information, Exchange (GENIE) database platform. Overall survival data of patients were obtained from cBioPortal. RESULTS: The median tumor mutation burden (TMB) was 5.18 per megabase. TP53 (65.5%), APC (59.5%), KRAS (36.9%), BRAF (20.2%), and RB1 (16.7%) were the most common genes harboring somatic mutations. Nearly all of the BRAF mutations (88.2%) caused V600E. The most common copy number alterations were gain of MYC (12.3%), loss of RB1 (10.7%), and loss of PTEN (5.4%). Compared to lung NEC and GI-NET, the genetic characteristics of CR-NEC were more similar to that of COREAD. CR-NEC had a higher rate of potentially targetable gene alterations compared to lung NEC and GI-NET, and BRAFV600E might be a promising treatment target. Survival analysis indicated that patients with high TMB had significantly worse survival than patients with low TMB (P < .001). In addition, KRAS and RB1 alteration were found to be correlated with worse survival (both P = .023). CONCLUSION: CR-NEC has genetic alterations that are more similar to COREAD than other entities. A substantial group of CR-NEC harboring potentially targetable alterations (BRAFV600E) deserves to be tested in clinical practice.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33043389

RESUMO

Several quorum sensing systems occurring in Bacillus subtilis, e.g. Rap-Phr systems, were reported to interact with major regulatory proteins, such as ComA, DegU, and Spo0A, in order to regulate competence, sporulation, and synthesis of secondary metabolites. In this study, we characterized a novel Rap-Phr system, RapA4-PhrA4, in Bacillus velezensis NAU-B3. We found that the rapA4 and phrA4 genes were co-transcribed in NAU-B3. When rapA4 was expressed in the heterologous host Bacillus subtilis OKB105, surfactin production and sporulation were severely inhibited. However, when the phrA4 was co-expressed, the RapA4 activity was inhibited. The transcription of the surfactin synthetase srfA gene and sporulation-related genes were also regulated by the RapA4-PhrA4 system. In vitro results obtained from electrophoretic mobility shift assay (EMSA) proved that RapA4 inhibits ComA binding to the promoter of the srfA operon, and the PhrA4 pentapeptide acts as anti-activator of RapA4. We also found that the F24 residue plays a key role in RapA4 function. This study indicated that the novel RapA4-PhrA4 system regulates the surfactin synthesis and sporulation via interaction with ComA, thereby supporting the bacterium to compete and to survive in a hostile environment. KEY POINTS: •Bacillus velezensis NAU-B3 has a novel Rap-Phr quorum sensing system, which does not occur in model strains Bacillus subtilis 168 and B. velezensis FZB42. •RapA4-PhrA4 regulates surfactin production and sporulation. •RapA4-PhrA4 interacts with the ComA protein from ComP/ComA two-component system.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33042001

RESUMO

Adipokines, including leptin, visfatin, adiponectin, and interleukin-6 (IL)-6, play multiple roles in the pathophysiology of epilepsy and febrile seizures (FS). We aimed to investigate the associations among plasma adipokines, mainly leptin, visfatin, adiponectin, or IL-6, and the prognosis of FS. This prospective cross-sectional study was conducted from January 2017 to December 2018 at the Wuxi Second People' Hospital China. The levels of serum leptin, visfatin, adiponectin, and IL-6 in 55 children with FS (FS group) were compared with 42 febrile children without seizure (FC group) and 48 healthy children (HC group) in an acute phase. The correlation with clinical indicators was determined by logistic regression analysis. Serum adiponectin and IL-6 levels were significantly higher in the FS group than in the FC and HC groups (p < 0.05), but there was no statistical difference between the FC and HC groups. In addition, logistic regression analysis showed that high concentrations of adiponectin and IL-6 were significantly associated with the occurrence of FS. For leptin and visfatin, they were significantly lower in the FS and FC groups than in the normal control group, but there was no statistical difference between the FS and FC groups. Our results suggest that higher plasma levels of IL-6 and adiponectin may serve as an additional biomarker in the early treatment or follow-up of the FS children.

5.
Updates Surg ; 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33048340

RESUMO

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.

6.
J Environ Radioact ; 225: 106446, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33065428

RESUMO

Micaceous minerals are the natural materials that can block radioactive strontium (Sr) released in the environment, and their adsorption capacity and mechanism are highly divergent owing to the different properties of micas. In this work, we comparatively studied the adsorption of Sr(II) on three typical micas, muscovite, biotite and phlogopite. The effects of pH, contact time, ionic strength, and background electrolyte were evaluated. It was found that phlogopite and muscovite had the largest solid-liquid distribution coefficient (Kd) for a reaction time of 48 h under acidic and alkaline conditions, respectively. Under alkaline conditions, as the reaction time increased to 44 days, phlogopite and muscovite showed the highest and lowest Kd, respectively. The Kd for Sr(II) adsorption on biotite and phlogopite increased with increasing pH but decreased with increasing pH for muscovite. X-ray diffraction analysis revealed that the interlayer weathering of phlogopite (a new diffraction peak appeared at 2-theta of ~6.1°) occurred along with the adsorption of Sr(II) below pH 9.0 under 0.01 mol/L NaCl. Furthermore, the adsorption of Sr(II) was significantly inhibited in the presence of 10-5 and 10-2 mol/L Cs+, resulting in similar adsorption capacity for phlogopite and muscovite at pH ~4.1. Consequently, the difference in Sr(II) adsorption on muscovite, biotite and phlogopite mainly came from the synergistic process of adsorption and weathering, which induced the differences in availability of interlayer sites among micas over a certain time.

7.
Biomed Pharmacother ; 132: 110821, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33068934

RESUMO

OBJECTIVE: The sodium-glucose transporter 2 (SGLT2) inhibitors Canagliflozin and Dapagliflozin are recently approved medications for type 2 diabetes. Recent studies indicate the potential ability of SGLT2 inhibitors to attenuate cancer growth of SGLT2-expressing cancer cells, but there is little known about the effects of SGLT2 inhibitors on breast cancer. The goal in this research was to assess the anticancer activity of SGLT2 inhibitors in breast cancerin vitro and in vivo. METHODS: We test the SGLT2 expression in breast cancer using immunohistochemistry and immunoblot assay. MTT cytotoxicity assay, colony formation assay and human breast cancer cells nude mice xenograft model were performed to detect the effects of SGLT2 inhibitors on cancer cell proliferation and growth. Flow Cytometry assay was performed to determine if the SGLT2 inhibitors induced cell cycle arrest and apoptosis. RESULTS: We proved that SGLT2 expresses in breast cancer cell lines and human breast tumor tissue samples. SGLT2 inhibitors Dapagliflozin and Canagliflozin exhibited a potent anti-proliferative effect in breast cancer cells as demonstrated by MTT, clonogenic survival assay in vitro and xenograft growth model in vivo. Furthermore, we found that SGLT2 inhibitors arrested cell cycle in G1/G0 phase and induced cell apoptosis. Western blot analysis demonstrated that treatment with SGLT2 inhibitors increased the phosphorylation of Amp-activated protein kinase (AMPK) and decreased the phosphorylation of 70 kDa ribosomal protein S6 kinase 1 (p70S6K1) in breast cancer cells. CONCLUSIONS: These findings indicate that SGLT2 inhibitor-therapy induced AMPK-mediated cell cycle arrest and apoptosis, which is a potential novel strategy for the treatment of breast cancer.

8.
Sci Rep ; 10(1): 17848, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33082509

RESUMO

To evaluate the imaging features of subungual glomus tumors using 18 MHz high-frequency ultrasound with CDFI (Color Doppler Flow Imaging). 20 patients treated by surgical resection and examined by ultrasound between January 2008 and December 2019. All eligible cases are divided into two groups: Group A used the probe frequency of 9-14 MHz from January 2008 to December 2014, and Group B used the probe frequency of 18 MHz from January 2015 to December 2019. Patient demographics, clinical records, pathologic specimens and sonography features were reviewed. 50% of tumors in Group A and 100% of tumors in Group B showed clear boundary and regular shape. Blood flow signals were identified inside 50% tumors in Group A (3 in 6), all 14 cases with blood flow signals detected in Group B (14 in 14,100%). 2 cases were misdiagnosed and 1 case escaped diagnosis in Group A, no case was misdiagnosed in Group B. The accuracy of diagnosis rate of Group B is significantly higher than that of Group A. 18-MHz ultrasound combined with CDFI may be a practical useful tool for detecting subungual glomus tumors. More importantly 18-MHz ultrasound can obviously improve the diagnostic accuracy.

9.
Hortic Res ; 7: 165, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33082971

RESUMO

Cerasus serrulata is a flowering cherry germplasm resource for ornamental purposes. In this work, we present a de novo chromosome-scale genome assembly of C. serrulata by the use of Nanopore and Hi-C sequencing technologies. The assembled C. serrulata genome is 265.40 Mb across 304 contigs and 67 scaffolds, with a contig N50 of 1.56 Mb and a scaffold N50 of 31.12 Mb. It contains 29,094 coding genes, 27,611 (94.90%) of which are annotated in at least one functional database. Synteny analysis indicated that C. serrulata and C. avium have 333 syntenic blocks composed of 14,072 genes. Blocks on chromosome 01 of C. serrulata are distributed on all chromosomes of C. avium, implying that chromosome 01 is the most ancient or active of the chromosomes. The comparative genomic analysis confirmed that C. serrulata has 740 expanded gene families, 1031 contracted gene families, and 228 rapidly evolving gene families. By the use of 656 single-copy orthologs, a phylogenetic tree composed of 10 species was constructed. The present C. serrulata species diverged from Prunus yedoensis ~17.34 million years ago (Mya), while the divergence of C. serrulata and C. avium was estimated to have occurred ∼21.44 Mya. In addition, a total of 148 MADS-box family gene members were identified in C. serrulata, accompanying the loss of the AGL32 subfamily and the expansion of the SVP subfamily. The MYB and WRKY gene families comprising 372 and 66 genes could be divided into seven and eight subfamilies in C. serrulata, respectively, based on clustering analysis. Nine hundred forty-one plant disease-resistance genes (R-genes) were detected by searching C. serrulata within the PRGdb. This research provides high-quality genomic information about C. serrulata as well as insights into the evolutionary history of Cerasus species.

10.
Water Res ; 188: 116481, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-33039830

RESUMO

Although permanganate activation by sodium sulfite (Mn(VII)/Na2SO3) has shown great potential for rapid abatement of organic contaminants, the limited reactivity under alkaline conditions and undesirable Mn residual may prevent its widespread application. To solve these challenges, calcium sulfite (CaSO3) was employed as a slow-release source of SO32-/HSO3- (S(IV)) to activate Mn(VII) in this study. It was found that the application of CaSO3 solid could extend the effective working pH range of Mn(VII)/S(IV) from ≤7.0 to ≤9.0. Moreover, due to the enhanced precipitation of MnO2 with the presence of Ca2+, very low Mn residual (<0.05 mg/L) was achieved in Mn(VII)/CaSO3 system. Mn(VII)/CaSO3 system is a unique two-stage oxidation process in terms of reaction kinetics and reactive oxidants. Specifically, Mn(VII) was rapidly consumed and reactive Mn intermediates (e.g., Mn(VI), Mn(V)), SO4•-, and HO• were produced in the first stage. However, the second stage was governed by the interaction between MnO2 and S(IV), with SO4•- and HO• serving as the dominant reactive oxidants. Taking advantage of an automatic titrator, excess S(IV) was found to greatly quench the generated radicals, whereas it did not cause a significant consumption of reactive Mn species. All these results improved our understanding of the Mn(VII)/S(IV) process and could thus facilitate its application.

11.
Kaohsiung J Med Sci ; 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33058411

RESUMO

Sepsis is caused by microbial infection with high mortality worldwide, and characterized by multiple organ dysfunction and systemic inflammatory response. Previous study shows that miR-181a level is increased during sepsis; however, the mechanism is still unknown. Therefore, to identify the role of miR-181a, lipopolysaccharide (LPS) was used to stimulate mouse peritoneal macrophages. The expressions of miR-181a and SIRT1 were identified by QRT-PCR, the levels of SIRT1, Nrf2, p-P65, Bcl-2 and Bax were detected by western blotting, the inflammatory cytokines TNF-α, IL-6 and IL-1ß were detected by ELISA, and the apoptosis was measured by flow cytometry. Bioinformatics and dual luciferase assay were used to unveil the binding sites and the targeted regulatory relationship of miR-181a and SIRT1. LPS induced the upregulation of miR-181a, downregulation of SIRT1 and a strong inflammatory response. In addition, LPS stimulation inhibited the expression of Nrf2 and activated the NF-κB pathway. Moreover, the inhibition of miR-181a attenuated inflammatory response and apoptosis during LPS stimulation, which was implemented by up-regulating the expression of its target SIRT1. More fully, downregulation of SIRT1 by short hairpin interference resulted in a decreased expression of Nrf2, increased expression of p-P65 and proinflammatory cytokines, and intensive apoptosis. Downregulation of miR-181a could promote the expression of its target SIRT1, and then, attenuate inflammatory response and apoptosis via Nrf2 and NF-κB signaling pathways during LPS treatment. miR-181a can be a potential target of controlling the inflammatory response during sepsis and has important clinical significance for the treatment and rehabilitation of septic patients.

12.
Neuroscience ; 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-33002559

RESUMO

Chylomicron Retention Disease (CMRD) is a rare inherited lipid malabsorption syndrome that exhibits a recessive hypocholesterolemia in infants. CMRD has been associated with genetic mutations of SAR1B-a member of the Arf GTPase family involved in the secretory pathway from the endoplasmic reticulum to the Golgi. CMRD patients suffer from multiple neurological deficits, the etiologies of which remain unclear. In this study, we found that Sar1b protein is expressed in developing mouse neocortex. The knockdown of Sar1b does not affect the proliferation and mitotic exit of the neural progenitors but inhibits the radial migration of the newborn cortical neurons. At postnatal day 3, the neurons stalled in the white matter fail to develop axons across the midline of the corpus callosum, resulting in the loss of the neurons later on. hSAR1B(D137N), a CMRD-associated mutant of SAR1B, also impairs the positioning of the cortical neurons in the mouse brain, suggesting a dominant-negative effect by the human heterozygous mutant. The results indicate that SAR1B is crucial to radial migration and axon morphogenesis of the cortical neurons. Our study reveals a cell-autonomous action of Sar1b, which is unrelated to lipid absorption from the gut, on the development of the cerebral cortex.

13.
Sci Rep ; 10(1): 17562, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33067499

RESUMO

Fluorinated graphene has a tunable band gap that is useful in making flexible graphene electronics. But the carbon-fluorine (C-F) bonds in fluorinated graphene can be easily broken by increased temperature or electron beam irradiation. Here, we demonstrate that the stability of fluorinated graphene is mainly determined by its C-F configuration. The double-sided fluorinated graphene has a much stronger stability than the single-sided fluorinated graphene under the same irradiation dose. Density functional theory calculations show that the configuration of double-sided fluorinated graphene has a negative and low formation energy, indicating to be an energetically stable structure. On the contrary, the formation energy of single-sided fluorinated graphene is positive, leading to an unstable C-F bonding that is easily broken by the irradiation. Our findings make a new step towards a more stable and efficient design of graphene electronic devices.

14.
Assist Technol ; : 1-8, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33048655

RESUMO

In the United States, wheeled mobility devices (WMD) are classified as durable medical equipment (DME). Consistent with the definition of DME, wheeled mobility devices are typically covered by health insurance when deemed medically necessary. Despite the number of persons using wheelchairs, little knowledge is available about the types of wheelchairs provided, user's specific diagnoses and the costs associated with WMD provision. The objective of this analysis was to define the number and types of wheelchairs and associated seating and mobility (S&M) accessories provided in the calendar year 2017. The analysis focused on user demographics, categories of WMDs and associated S&M equipment as well as cost accounting according to the type of insurance and contributions by beneficiaries. Analysis of over 81,000 wheelchair acquisitions found that manual wheelchairs accounted for nearly 90% with standard manual wheelchairs accounting for 86% of all wheelchairs provided. Wheelchair recipients tended to be older with the majority being female. Based upon ICD-10 diagnostic categories over 50% of captured ICD-10 codes came from three classifications, musculoskeletal (M), circulatory (I) and a general category of not otherwise classified disorders (R). Costs associated with seating and mobility equipment were fairly large, exceeding $79 million over a single calendar year.

15.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 5240-5243, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33019166

RESUMO

Depression is expected to be one of the significant global medical burdens. Ultrasound therapy, with much-encouraging evidence, has been demonstrated to have a beneficial effect on alleviating mental illness symptoms (neuropsychiatric conditions). However, the study of estimating the risk of using transcranial therapeutic ultrasound has barely been investigated. In this experiment, we develop a wearable head-mounted LIPUS device and assessed the possible tissue damage when applying the LIPUS stimulation on the brain. Our computer simulation and in-vitro experiment results demonstrate that the low-intensity ultrasound (LIPUS) device can safely deliver small doses of low-intensity pulsed ultrasound through the skull into the brain without significant thermal injury. The preliminary results indicate that this modality has the potential for the transcranial treatment of neurological diseases in safety.

16.
Sensors (Basel) ; 20(19)2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33019643

RESUMO

Autonomous driving with artificial intelligence technology has been viewed as promising for autonomous vehicles hitting the road in the near future. In recent years, considerable progress has been made with Deep Reinforcement Learnings (DRLs) for realizing end-to-end autonomous driving. Still, driving safely and comfortably in real dynamic scenarios with DRL is nontrivial due to the reward functions being typically pre-defined with expertise. This paper proposes a human-in-the-loop DRL algorithm for learning personalized autonomous driving behavior in a progressive learning way. Specifically, a progressively optimized reward function (PORF) learning model is built and integrated into the Deep Deterministic Policy Gradient (DDPG) framework, which is called PORF-DDPG in this paper. PORF consists of two parts: the first part of the PORF is a pre-defined typical reward function on the system state, the second part is modeled as a Deep Neural Network (DNN) for representing driving adjusting intention by the human observer, which is the main contribution of this paper. The DNN-based reward model is progressively learned using the front-view images as the input and via active human supervision and intervention. The proposed approach is potentially useful for driving in dynamic constrained scenarios when dangerous collision events might occur frequently with classic DRLs. The experimental results show that the proposed autonomous driving behavior learning method exhibits online learning capability and environmental adaptability.

17.
J Mater Chem B ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33021308

RESUMO

Core decompression of the femoral head is a recommended head-conserving strategy for early-stage osteonecrosis of the femoral head. However, no ideal filling material has been found so far. In this study, we fabricated a "solid core-porous coating" composite scaffold, which is a silk fibroin/hydroxypropyl methylcellulose (SF/HPMC) scaffold, by a "two-step" process. The solid core scaffold possesses a sufficient compression modulus (860 MPa) for support, while the porous coating scaffold with controllable pore size and porosity provides a suitable microenvironment for the osteoblast cell to adhere and proliferate. Moreover, the porous coating scaffold was mineralized by adding different contents of hydroxyapatite crystal to further enhance its osteoinductivity, according to the simulated body fluid (SBF) biomineralization assay. To demonstrate the biocompatibility and osteoinductivity of such composite scaffolds, a series of in vitro experiments were performed, indicating the MC3T3-E1 pre-osteoblast cells grew and differentiated well on the mineralized porous coating scaffolds. The mechanical testing results also proved that the mechanical property of the solid core scaffold varied (230-1600 MPa) with different solid contents of SF/HPMC, as expected. Furthermore, the rabbit femoral head core decompression model was adopted and confirmed the excellent mechanical performance of the solid core scaffolds, as well as the satisfied osteoinductivity of the porous coating scaffold, by inserting the composite scaffolds into the bone tunnel in vivo. All of the preliminary results implied that the novel biodegradable composite scaffold has an outstanding prospective for the clinical use of core decompression of the femoral head.

18.
Pediatr Res ; 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33007780

RESUMO

BACKGROUND: Intranasal corticosteroids are the most efficacious anti-inflammatory medications for allergic rhinitis (AR). However, the efficacy and safety of intranasal corticosteroids in children have not yet been subject to specific research in China. The aim of this study was to investigate the efficacy and safety of fluticasone furoate nasal spray (FFNS) in a Chinese pediatric population. METHODS: In this phase 4 randomized, double-blind, placebo-controlled, multicenter study, pediatric AR patients aged 2-12 years were randomized 1:1:1, receiving either FFNS 55 µg or 110 µg or placebo. Electronic diary cards were completed to record symptoms, rescue medication use, and treatment compliance. Anterior rhinoscopy and overall response to therapy were evaluated and recorded. RESULTS: Patients treated with FFNS at either dose experienced a significantly greater reduction in daily reflective total nasal symptom score compared with placebo. This was maintained in a younger subset of patients (2-6 years). Drug-related adverse events occurred in <20% of patients in all groups. FFNS was well tolerated at both doses. CONCLUSIONS: This study demonstrates favorable efficacy and safety profiles for FFNS 55 µg or 110 µg in Chinese pediatric populations (2-12 years), supporting its use in clinical treatment for AR children, including younger children aged 2-6 years. IMPACT: The aim of this study was to investigate the efficacy and safety of intranasal fluticasone furoate in Chinese pediatric allergic rhinitis. This research not only addresses the deficiency in efficacy and safety data for intranasal corticosteroids in very young patients (aged 2-6 years) worldwide but also demonstrates that fluticasone furoate nasal spray shows a favorable benefit/risk profile at different dose levels. Our data will be of interest to the broad readership of Pediatric Research and will positively contribute to the dialog regarding the treatment of allergic rhinitis in children aged 2-6 years.

19.
Sci Adv ; 6(40)2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32998884

RESUMO

Immune checkpoint blockade therapy (ICT) has shown potential in the treatment of multiple tumors, but suffers poor response rate in clinic. We found that even combining ICT with chemotherapy, which was wildly used in clinical trials, failed to achieve satisfactory tumor inhibition in the B16F10 model. Thus, we further constructed a previously unexplored immune cocktail therapy and realized multiple boosting of the cancer-immunity cycle. Cocktail therapy consisted of two kinds of tumor microenvironment-responsive drug and gene delivery nanoparticles to achieve specific delivery of doxorubicin and codelivery of plasmids expressed small hairpin RNA of PD-L1 (pshPD-L1) and hyaluronidase (pSpam1) in the tumor area. Experimental evidences proved that any component in the cocktail therapy was indispensable, and the cocktail therapy exhibited excellent antitumor effects against different types of tumors. The cocktail therapy presented here offers a searching strategy for more synergistic units with ICT and is meaningful for developing more efficient antitumor immunotherapy.

20.
Pharm Dev Technol ; : 1-9, 2020 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-33070673

RESUMO

Multidrug resistance (MDR) is a serious challenge in chemotherapy and also a major threat to breast cancer treatment. As an intracellular energy factory, mitochondria provide energy for drug efflux and are deeply involved in multidrug resistance. Mitochondrial targeted delivery of doxorubicin can overcome multidrug resistance by disrupting mitochondrial function. By incorporating a reactive oxygen species (ROS)-responsive hydrophobic group into the backbone structure of hyaluronic acid - a natural ligand for the highly expressed CD44 receptor on tumor surfaces, a novel ROS-responsive and CD44-targeting nano-carriers was constructed. In this study, mitochondria-targeted triphenylphosphine modified-doxorubicin (TPP-DOX) and amphipathic ROS-responsive hyaluronic acid derivatives (HA-PBPE) were synthesized and confirmed by 1H NMR. The nanocarriers TPP-DOX @ HA-PBPE was prepared in a regular shape and particle size of approximately 200 nm. Compared to free DOX, its antitumor activity in vitro and tumor passive targeting in vivo has been enhanced. The ROS-responsive TPP-DOX@HA-PBPE nanocarriers system provide a promising strategy for the reverse of MDR and efficient delivery of doxorubicin derivatives into drug-resistant cancer cells.

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