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2.
Artigo em Inglês | MEDLINE | ID: mdl-32401477

RESUMO

High-quality precursor solution is essential for the fabrication of hybrid perovskite solar cells. This paper reports a simple and efficient method of preparing the high-quality concentrated solution of methylammonium triiodoplumbate (MAPbI3) in N,N-dimethyl formamide (DMF) by using MAPbI3 crystal instead of conventional lead iodine and methylammonium iodine blend. The MAPbI3 concentration of the precursor solution is easily and accurately adjusted from zero up to 1.64 M. The investigation on the dissolution process of the MAPbI3 crystal reveals that the concentrated solution of MAPbI3 in DMF is metastable, and transition from the concentrated solution to solvated intermediate MAPbI3∙DMF determines the solubility of MAPbI3 in DMF. The high purity and precise stoichiometric ratio of the crystal eliminate the possible impurities that initialize the transition to MAPbI3∙DMF, and consequently suppress the transition and increase the stability of the concentrated solution. MAPbI3 films with different thickness up to 800 nm are prepared with conventional film fabrication technique, and a highest power conversion efficiency of 20.7% is achieved on corresponding solar cells. The newly developed method to prepare the concentrated precursor solution can be easily combined with other fabrication techniques for the further development of industrial-scale manufacture of solar cells.

3.
Lancet Oncol ; 2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32416072

RESUMO

BACKGROUND: Isocitrate dehydrogenase 1 (IDH1) mutations occur in approximately 13% of patients with intrahepatic cholangiocarcinoma, a relatively uncommon cancer with a poor clinical outcome. The aim of this international phase 3 study was to assess the efficacy and safety of ivosidenib (AG-120)-a small-molecule targeted inhibitor of mutated IDH1-in patients with previously treated IDH1-mutant cholangiocarcinoma. METHODS: This multicentre, randomised, double-blind, placebo-controlled, phase 3 study included patients from 49 hospitals in six countries aged at least 18 years with histologically confirmed, advanced, IDH1-mutant cholangiocarcinoma who had progressed on previous therapy, and had up to two previous treatment regimens for advanced disease, an Eastern Cooperative Oncology Group performance status score of 0 or 1, and a measurable lesion as defined by Response Evaluation Criteria in Solid Tumors version 1.1. Patients were randomly assigned (2:1) with a block size of 6 and stratified by number of previous systemic treatment regimens for advanced disease to oral ivosidenib 500 mg or matched placebo once daily in continuous 28-day cycles, by means of an interactive web-based response system. Placebo to ivosidenib crossover was permitted on radiological progression per investigator assessment. The primary endpoint was progression-free survival by independent central review. The intention-to-treat population was used for the primary efficacy analyses. Safety was assessed in all patients who had received at least one dose of ivosidenib or placebo. Enrolment is complete; this study is registered with ClinicalTrials.gov, NCT02989857. FINDINGS: Between Feb 20, 2017, and Jan 31, 2019, 230 patients were assessed for eligibility, and as of the Jan 31, 2019 data cutoff date, 185 patients were randomly assigned to ivosidenib (n=124) or placebo (n=61). Median follow-up for progression-free survival was 6·9 months (IQR 2·8-10·9). Progression-free survival was significantly improved with ivosidenib compared with placebo (median 2·7 months [95% CI 1·6-4·2] vs 1·4 months [1·4-1·6]; hazard ratio 0·37; 95% CI 0·25-0·54; one-sided p<0·0001). The most common grade 3 or worse adverse event in both treatment groups was ascites (four [7%] of 59 patients receiving placebo and nine [7%] of 121 patients receiving ivosidenib). Serious adverse events were reported in 36 (30%) of 121 patients receiving ivosidenib and 13 (22%) of 59 patients receiving placebo. There were no treatment-related deaths. INTERPRETATION: Progression-free survival was significantly improved with ivosidenib compared with placebo, and ivosidenib was well tolerated. This study shows the clinical benefit of targeting IDH1 mutations in advanced, IDH1-mutant cholangiocarcinoma. FUNDING: Agios Pharmaceuticals.

4.
Cancer Chemother Pharmacol ; 85(5): 959-968, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32296873

RESUMO

PURPOSE: Isocitrate dehydrogenase (IDH) mutations lead to formation of the oncometabolite 2-hydroxyglutarate (2-HG), which is elevated in several solid and liquid tumors. Ivosidenib (AG-120) is a targeted, potent, oral inhibitor of the mutant IDH1 protein. We describe detailed pharmacokinetics and pharmacodynamics of ivosidenib in patients with advanced hematologic malignancies with an IDH1 mutation treated in a phase I study (ClinicalTrials.gov NCT02074839). METHODS: Patients received single and multiple oral doses of ivosidenib from 100 mg twice daily to 1200 mg once daily (QD) in 28-day continuous cycles. Concentrations of ivosidenib and 2-HG in plasma, and 2-HG in bone marrow, were assessed at routine intervals. Plasma 4ß-hydroxycholesterol/cholesterol ratios were assessed as a marker of CYP3A activity. RESULTS: Ivosidenib was rapidly absorbed and slowly eliminated (half-life 72-138 h) after single and multiple dosing. Ivosidenib exhibited dose- and time-dependent pharmacokinetics, with exposure increasing sub-proportionally to dose, and clearance increasing with increasing dose. Plasma 2-HG concentrations were maximally and persistently inhibited in the majority of patients receiving 500-mg QD ivosidenib, to concentrations close to those observed in healthy subjects. Ivosidenib pharmacokinetics were not affected by mild or moderate renal impairment, mild hepatic impairment, age, weight, sex, race, or co-administration of weak CYP3A4 inhibitors or inducers. Moderate-to-strong CYP3A4 inhibitors decreased ivosidenib clearance. Ivosidenib also induced CYP3A enzyme activity, with increases in 4ß-hydroxycholesterol/cholesterol ratios of 119-168% at 500-mg QD ivosidenib. CONCLUSIONS: Ivosidenib 500-mg QD has favorable pharmacokinetic and pharmacodynamic profiles in patients with advanced hematologic malignancies with an IDH1 mutation. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT02074839.

5.
Disaster Med Public Health Prep ; : 1-16, 2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32317031

RESUMO

Disasters such as earthquake, flood, epidemics usually lead to large numbers of casualties accompanied by disruption of the functioning of local medical institutions. A rapid response of medical assistance and support are required. Mobile hospitals have been deployed by national and international organizations at disaster situations in the past decades, which play an important role in saving casualties and alleviating shortage of medical resources. In this paper, we briefly introduce the types and characteristics of mobile hospitals used by medical teams in disaster rescue, including the aspects of structural form, organizational form and mobile transportation. We also review the practices of mobile hospitals in disaster response, summarize the problems and needs of mobile hospitals in disaster rescue. Finally, we propose the development direction of mobile hospitals, especially on the development of intelligence, rapid deployment capabilities and modularization, which provide suggestions for further research and development of mobile hospitals in the future.

6.
Cancer Med ; 2020 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-32239802

RESUMO

Intraductal papillary mucinous neoplasm (IPMN) is an intraepithelial precancerous lesion of pancreatic ductal adenocarcinoma (PDAC) that progresses from adenoma to carcinoma, and long noncoding RNAs (lncRNA) might be involved in the tumorigenesis. In this study, we obtained the expression profiles of more than 4000 lncRNAs by probe reannotation of a microarray dataset. As a correlation network-based systems biology method, weighted gene coexpression network analysis (WGCNA) was used to find clusters of highly correlated lncRNAs in the tumorigenesis of IPMN, which covered four stepwise stages from normal main pancreatic duct to invasive IPMN. In the most relevant module (R2  = -0.75 and P = 5E-05), three hub lncRNAs were identified (HAND2-AS1, CTD-2033D15.2, and lncRNA-TFG). HAND2-AS1 and CTD-2033D15.2 were negatively correlated with the tumorigenesis (P in one-way ANOVA test = 1.45E-07 and 1.39E-0.5), while lncRNA-TFG were positively correlated with the tumorigenesis (P = 3.99E-08). The validation set reached consistent results (P = 2.66E-03 in HAND2-AS1, 1.47E-04 in CTD-2033D15.2 and 6.23E-08 in lncRNA-TFG). In functional enrichment analysis, the target genes of microRNAs targeting also these lncRNAs were overlapped in multiple biological processes, pathways and malignant diseases including pancreatic cancer. In survival analysis, patients with higher expression of HAND2-AS1-targeted and CTD-2033D15.2-targeted microRNAs showed a significantly poorer prognosis in PDAC, while high expression of lncRNA-TFG-targeted microRNAs demonstrated an obviously better prognosis (log-rank P < .05). In conclusion, by coexpression network analysis of the lncRNA profiles, three key lncRNAs were identified in association with the tumorigenesis of IPMN, and those lncRNAs might act as early diagnostic biomarkers or therapeutic targets in pancreatic cancer.

7.
J Clin Oncol ; 38(15): 1693-1701, 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32208957

RESUMO

PURPOSE: Surgery is the primary therapy for localized chondrosarcoma; for locally advanced and/or metastatic disease, no known effective systemic therapy exists. Mutations in the isocitrate dehydrogenase 1/2 (IDH1/2) enzymes occur in up to 65% of chondrosarcomas, resulting in accumulation of the oncometabolite D-2-hydroxyglutarate (2-HG). Ivosidenib (AG-120) is a selective inhibitor of mutant IDH1 approved in the United States for specific cases of acute myeloid leukemia. We report outcomes of patients with advanced chondrosarcoma in an ongoing study exploring ivosidenib treatment. PATIENTS AND METHODS: This phase I multicenter open-label dose-escalation and expansion study of ivosidenib monotherapy enrolled patients with mutant IDH1 advanced solid tumors, including chondrosarcoma. Ivosidenib was administered orally (100 mg twice daily to 1,200 mg once daily) in continuous 28-day cycles. Responses were assessed every other cycle using RECIST (version 1.1). RESULTS: Twenty-one patients (escalation, n = 12; expansion, n = 9) with advanced chondrosarcoma received ivosidenib (women, n = 8; median age, 55 years; range, 30-88 years; 11 had received prior systemic therapy). Treatment-emergent adverse events (AEs) were mostly grade 1 or 2. Twelve patients experienced grade ≥ 3 AEs; only one event was judged treatment related (hypophosphatemia, n = 1). Plasma 2-HG levels decreased substantially in all patients (range, 14%-94.2%), to levels seen in healthy individuals. Median progression-free survival (PFS) was 5.6 months (95% CI, 1.9 to 7.4 months); the PFS rate at 6 months was 39.5%. Eleven (52%) of 21 patients experienced stable disease. CONCLUSION: In patients with chondrosarcoma, ivosidenib showed minimal toxicity, substantial 2-HG reduction, and durable disease control. Future studies of ivosidenib monotherapy or rational combination approaches should be considered in patients with advanced mutant IDH1 chondrosarcoma.

8.
Cell Commun Signal ; 18(1): 27, 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32066462

RESUMO

BACKGROUND: Excessive light exposure is a detrimental environmental factor that plays a critical role in the pathogenesis of retinal degeneration. However, the mechanism of light-induced death of retina/photoreceptor cells remains unclear. The mammalian/mechanistic target of rapamycin (mTOR) and Poly (ADP-ribose) polymerase-1 (PARP-1) have become the primary targets for treating many neurodegenerative disorders. The aim of this study was to elucidate the mechanisms underlying light-induced photoreceptor cell death and whether the neuroprotective effects of mTOR and PARP-1 inhibition against death are mediated through apoptosis-inducing factor (AIF). METHODS: Propidium iodide (PI)/Hoechst staining, lentiviral-mediated short hairpin RNA (shRNA), Western blot analysis, cellular fraction separation, plasmid transient transfection, laser confocal microscopy, a mice model, electroretinography (ERG), and hematoxylin-eosin (H & E) staining were employed to explore the mechanisms by which rapamycin/3-Aminobenzamide (3AB) exert neuroprotective effects of mTOR/PARP-1 inhibition in light-injured retinas. RESULTS: A parthanatos-like death mechanism was evaluated in light-injured 661 W cells that are an immortalized photoreceptor-like cell line that exhibit cellular and biochemical feature characteristics of cone photoreceptor cells. The death process featured over-activation of PARP-1 and AIF nuclear translocation. Either PARP-1 or AIF knockdown played a significantly protective role for light-damaged photoreceptors. More importantly, crosstalk was observed between mTOR and PARP-1 signaling and mTOR could have regulated parthanatos via the intermediate factor sirtuin 1 (SIRT1). The parthanatos-like injury was also verified in vivo, wherein either PARP-1 or mTOR inhibition provided significant neuroprotection against light-induced injury, which is evinced by both structural and functional retinal analysis. Overall, these results elucidate the mTOR-regulated parthanatos death mechanism in light-injured photoreceptors/retinas and may facilitate the development of novel neuroprotective therapies for retinal degeneration diseases. CONCLUSIONS: Our results demonstrate that inhibition of the mTOR/PARP-1 axis exerts protective effects on photoreceptors against visible-light-induced parthanatos. These protective effects are conducted by regulating the downstream factors of AIF, while mTOR possibly interacts with PARP-1 via SIRT1 to regulate parthanatos. Video Abstract Schematic diagram of mTOR interacting with PARP-1 to regulate visible light-induced parthanatos. Increased ROS caused by light exposure penetrates the nuclear membrane and causes nuclear DNA strand breaks. PARP-1 detects DNA breaks and synthesizes PAR polymers to initiate the DNA repair system that consumes a large amount of cellular NAD+. Over-production of PAR polymers prompts the release of AIF from the mitochondria and translocation to the nucleus, which leads to parthanatos. Activated mTOR may interact with PARP-1 via SIRT1 to regulate visible light-induced parthanatos.

9.
ACS Nano ; 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32023036

RESUMO

Exploiting stretchable solar cells that can accommodate large strain and feature high cyclic mechanical endurance is challenging for wearable and skin-interfaced electronics application. In this work, we demonstrated such solar cells using the kirigami design. Experiments and mechanical simulations showed that the kirigami structure effectively imparted stretchability to perovskite solar cells (PSCs) through out-of-plane deformation, which significantly reduced the stress in devices. The kirigami-based PSCs with optimal geometric parameters exhibited high mechanical deformability, including stretchability (strain up to 200%), twistability (angle up to 450°), and bendability (radius down to 0.5 mm). More importantly, the kirigami PSCs revealed high mechanical endurance with almost unchanged performance even after 1000 repetitive stretching, twisting, and bending cycles. This kirigami design for stretchable PSCs presented here provides a promising strategy to achieve high deformability for solar cells as well as other optoelectronic devices.

10.
Am J Physiol Cell Physiol ; 318(2): C272-C281, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31747314

RESUMO

The IL-6/STAT3 signaling pathway is required for the development of psoriatic lesions, and tripartite motif-containing 27 (TRIM27) is a protein inhibitor of activated STAT3 (PIAS3)-interacting protein that could modulate IL-6-induced STAT3 activation. However, whether TRIM27 is associated with the IL-6/STAT3 signaling pathway in psoriasis remains enigmatic. TRIM27 expression and gene set enrichment analysis in patients with psoriasis were determined using bioinformatics. Human keratinocyte HaCaT cells treated with recombinant protein IL-6 (rh-IL-6) were transduced with lentivirus silencing TRIM27 and/or PIAS3 or, otherwise, transduced with lentivirus expressing TRIM27 and/or lentivirus silencing STAT3, or MG132, a proteasome-specific protease inhibitor. Cell proliferation and inflammation factor production were measured using Cell Counting Kit-8 and ELISA, respectively. TRIM27, proliferation marker protein Ki-67 (Ki67), phospho-STAT3 (p-STAT3), STAT3, and PIAS3 expressions were determined using real-time quantitative PCR, immunofluorescence staining, or Western blot analysis. Coimmunoprecipitation combined with ubiquitination analysis was performed to explore the interaction between TRIM27 and PIAS3. In the present study, TRIM27 expression was increased in psoriatic lesions, associated with the IL-6 signaling pathway, and induced by rh-IL-6 in a time-dependent manner. The increased cell proliferation, inflammation factor production, and expression of Ki67 and of p-STAT3 relative to STAT3 induced by rh-IL-6 and TRIM27 overexpression were significantly inhibited by TRIM27 silencing and STAT3 silencing, respectively. More importantly, TRIM27 interacted with PIAS3, and its overexpression promoted PIAS3 ubiquitination in HaCaT cells. PIAS3 silencing also significantly promoted TRIM27-dependent and IL6-induced STAT3 activation, cell proliferation, and inflammation factor production. In conclusion, our results highlight that TRIM27 expression is significantly increased by IL-6 and suggest a TRIM27/STAT3-dependent mechanism for regulation of inflammation and proliferation-associated development of psoriasis.

11.
Zool Res ; 41(1): 61-69, 2020 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-31709784

RESUMO

Tylorrhynchus heterochaetus is a widespread benthic polychaete worm found in coastal brackish waters of the west Pacific. It has high ecological and economic value as a biomarker of water quality and as a high-quality feed in aquaculture and fisheries and is considered a delicacy in some areas of Asia. However, it has experienced a marked reduction in recent years due to overexploitation as well as changes in the environment and climate. Here, to comprehensively understand its genetic background and thus provide insights for better conservation and utilization of this species, we assessed the genetic variability and demographic history of T. heterochaetus individuals sampled from eight locations along the coasts of southeast China and north Vietnam based on mitochondrial cytochrome c oxidase I ( COI) sequences. We observed high haplotype diversity ( Hd), with an average of 0.926, but relatively low nucleotide diversity ( π), with a mean of 0.032 across all samples. A total of 94 polymorphic sites and 85 haplotypes were identified among 320 individuals. The pairwise genetic distances among haplotypes ranged from 0.001 to 0.067, with the high intraspecific divergence possibly reflecting geographic isolation and gene pool fragmentation. Significant genetic structures were revealed among the studied locations; specifically, the eight locations could be treated as six genetically different populations based on pairwise Φ ST results (0.026-0.951, P<0.01). A significant pattern of isolation-by-distance was detected between the genetic and geographic distances ( r=0.873, P=0.001). Three geographic lineages were defined based on phylogenetic tree and network analyses of COI haplotypes. AMOVA results indicated that genetic variations mainly occurred among the three lineages (89.96%). Tests of neutrality and mismatch distribution suggested that T. heterochaetus underwent recent population expansion. These results provide the first report on the genetic status of T. heterochaetus and will be valuable for the management of genetic resources and better understanding of the ecology and evolution in this species.


Assuntos
Distribuição Animal , DNA Mitocondrial/genética , Variação Genética , Poliquetos/genética , Animais , China , Filogenia , Vietnã
12.
Blood ; 135(7): 463-471, 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-31841594

RESUMO

Ivosidenib (AG-120) is an oral, targeted agent that suppresses production of the oncometabolite 2-hydroxyglutarate via inhibition of the mutant isocitrate dehydrogenase 1 (IDH1; mIDH1) enzyme. From a phase 1 study of 258 patients with IDH1-mutant hematologic malignancies, we report results for 34 patients with newly diagnosed acute myeloid leukemia (AML) ineligible for standard therapy who received 500 mg ivosidenib daily. Median age was 76.5 years, 26 patients (76%) had secondary AML, and 16 (47%) had received ≥1 hypomethylating agent for an antecedent hematologic disorder. The most common all-grade adverse events were diarrhea (n = 18; 53%), fatigue (n = 16; 47%), nausea (n = 13; 38%), and decreased appetite (n = 12; 35%). Differentiation syndrome was reported in 6 patients (18%) (grade ≥3 in 3 [9%]) and did not require treatment discontinuation. Complete remission (CR) plus CR with partial hematologic recovery (CRh) rate was 42.4% (95% confidence interval [CI], 25.5% to 60.8%); CR 30.3% (95% CI, 15.6% to 48.7%). Median durations of CR+CRh and CR were not reached, with 95% CI lower bounds of 4.6 and 4.2 months, respectively; 61.5% and 77.8% of patients remained in remission at 1 year. With median follow-up of 23.5 months (range, 0.6-40.9 months), median overall survival was 12.6 months (95% CI, 4.5-25.7). Of 21 transfusion-dependent patients (63.6%) at baseline, 9 (42.9%) became transfusion independent. IDH1 mutation clearance was seen in 9/14 patients achieving CR+CRh (5/10 CR; 4/4 CRh). Ivosidenib monotherapy was well-tolerated and induced durable remissions and transfusion independence in patients with newly diagnosed AML. This trial was registered at www.clinicaltrials.gov as #NCT02074839.

13.
Curr Med Sci ; 39(6): 990-996, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31845232

RESUMO

This study explored the feasibility of employing computer-aided design (CAD) and 3 dimensional (3D)-printed personalized guide plate for the mini-invasive percutaneous internal screw fixation of fractured scaphoid. The study consisted of two parts: (1) experimentation on upper limbs from corpses and (2) preliminary clinical application. Corpse experiments involved upper limbs of 6 adult corpses. The specimens of upper limbs were subjected to plain CT scan. Then the CT data were input into computer to conduct 3D reconstruction of wrist region. The direction and depth of the guide wire and screw were designed on the basis of the principle that screw should lie at the center of scaphoid and the long axis of the screw should be aligned with that of the scaphoid. The carpal bone model and the guide plate were designed and 3D-printed. By using the guide plates, the guide wire was placed and the cannulated compression screw was inserted. The wrist region was examined by X-ray and CT to observe the location of the screw in the scaphoid. The scaphoid was longitudinally excised to grossly observe the location and evaluate the result of screw insertion. For clinical application, the guide plate was employed in 4 patients with fresh scaphoid fracture using the aforementioned operative technique. Our results showed that, in the 6 corpse limbs, the guide plate well fitted the skin surface and the guide wire and screw were accurately put in place in one session. X-ray examination and gross observation confirmed that the screw was satisfactorily positioned and the result met the requirements of the preoperative design. For 4 patients, the guide wire and screw were all precisely inserted into place in one session. The operation time and X-ray exposure times were apparently reduced. The imaging examination exhibited satisfactory results and the hand functioned well. It was concluded that the operative guide plate used for the mini-invasive percutaneous internal screw fixation of fractured scaphoid not only can assist in accurate placement of screw but also shorten operation time and reduce insertion and X-ray exposure times, thereby reducing the radiation injury and damage to the substance and the blood circulation of carpal bone. Its use can also improve the learning curve of surgeons.


Assuntos
Fixação Interna de Fraturas/instrumentação , Fraturas Ósseas/cirurgia , Impressão Tridimensional/instrumentação , Osso Escafoide/lesões , Adulto , Parafusos Ósseos , Cadáver , Estudos de Viabilidade , Feminino , Fraturas Ósseas/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Osso Escafoide/diagnóstico por imagem , Osso Escafoide/cirurgia , Tomografia Computadorizada por Raios X , Resultado do Tratamento
14.
Appl Opt ; 58(36): 9976-9982, 2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31873644

RESUMO

It is well known that the superposition of two identical random dot patterns may give rise to a particular form of moiré effect known as a Glass pattern. By integrating a microlens array and a micropattern array and applying a small geometrical transformation, it is possible to show the parallactic or the orthoparallactic motion effect when varying the viewing angle. In this paper, we study the effect of the structural parameters of a Glass pattern optical system on its image quality. The position of each elemental pattern in the micropattern array is derived based on a revised model that considers the finite observation distance. The image quality is evaluated by the ray analysis on the observation plane and the reconstructed image plane. Rays from different pixels of the micropattern array are evaluated by the spot size. The depth of the Glass pattern in image space is also analyzed. In addition, a Glass pattern optical system is simulated and optimized by ZEMAX software. An optimal result is obtained that validates the theoretical analysis. Our study can find potential application for designing Glass pattern optical systems or optimization of those imaging systems based on microlens arrays.

15.
Curr Drug Deliv ; 16(8): 751-758, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31722658

RESUMO

BACKGROUND: Curcumin has shown considerable pharmacological activity, including antiinflammatory activity. Nevertheless, the pharmacological effect of curcumin may be limited because of poor water solubility, metabolizing rapidly and systemic elimination. OBJECTIVE: In the current research, a novel curcumin nanoemulsion (Cur-NE) was developed for improving in vitro permeability and bioavailability via pulmonary administration. METHODS: The Cur-NE was prepared by a modified emulsification-evaporation method and its surfac morphology, particles size and distribution, and encapsulation efficiencies of drug in NE were characterized. In vitro transmembrane transport experiment was performed to investigate the transport profile of curcumin across Xenopus alveolar membrane. The pharmacokinetics of Cur-NE in rabbits was evaluated. RESULTS: The average particles size, zeta potential, polydispersity index of Cur-NE were 234.8±1.08 nm, -19.5±0.2 mV and 0.10, respectively. Xenopus alveolar membrane was used in the transmembrane transport study, the cumulative amount of curcumin was 6.6% for curcumin suspensions, but nearly 50% for Cur-NE at the time of 8 h (P<0.05). The pharmacokinetic study in rabbits, the absolute bioavailability of curcumin for Cur-NE was 24.11%. CONCLUSION: Thus, a novel Cur-NE for pulmonary drug delivery was developed for improving in vitro permeability and bioavailability, which can be an alternate to the oral administration.

16.
Int J Anal Chem ; 2019: 6217125, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31391851

RESUMO

Shenfu Tang and Dushen Tang (one of the composite medicines for Shenfu Tang) are widely used Traditional Chinese herbal formulations and ginsenosides are their main bioactive components. However, there are rare studies about simultaneous analysis of ginsenosides in Shenfu Tang and Dushen Tang. In order to identify ginsenosides in Shenfu Tang and Dushen Tang and to explore law of compatibility of medicines in the decoction, a method for simultaneous determination of twelve ginsenosides in Shenfu Tang and Dushen Tang was developed by ultraresolution liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS). The method showed satisfactory linearity (r > 0.9915), repeatability (RSD < 9.58%), intra- and interday precisions (RSD<11.90%), and high yields of recovery (92.26-113.20%) for twelve major constituents, namely, ginsenosides-Rb1, Rb2, Rb3, Rc, Rd, Rg1, Re, Rf, Rg2, Rg3, Rh1, and F2. Furthermore, the concentration of twelve ginsenosides in Dushen Tang and Shenfu Tang was also simultaneously analyzed. Most of ginsenosides except Rg1 and Rb1 showed higher contents in Shenfu Tang compared to Dushen Tang. The compatibility of the formula had the effect of promoting or inhibiting the dissolution of some major components. The present research provided a reliable evidence for the illustration of chemical basis and compatibility regularity of Shenfu Tang. This study demonstrated the utility of the developed method for assessment of the quantity of the major constituents in Dushen Tang and Shenfu Tang.

17.
J Sep Sci ; 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31397973

RESUMO

A rapid, sensitive, and widely applicable method for the simultaneous quantitative analysis of 20 underivatized amino acids in different biological matrices, including serum, plasma, and tissue homogenates, using ultra high performance liquid chromatography with tandem mass spectrometry was developed and validated. Only 4 µL of serum, plasma, or tissue homogenate was extracted with 996 µL of solution (1.7 mM ammonium formate in 85% acetonitrile containing 0.1% formic acid) containing 100 ng/mL phenylalanine-d5 as an internal standard without any further derivatization step. In addition, the matrix effects were small because a large volume of extraction solution was used. The total run time including reequilibration was 13 min. The results of linearity, accuracy, repeatability, precision, limits of detection, limits of quantification, and sample stability were sufficient to allow the measurement of the amino acids in different biological matrices. We conclude that our method is rapid, sensitive, and widely applicable and represents an improvement over other currently available technologies.

18.
Int J Mol Med ; 44(4): 1233-1242, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31364726

RESUMO

Cyclocarya paliurus (CP) polysaccharide (CPP) is a chemical component contained in CP, which has been reported to possess significant hypoglycemic activity. The present study aimed to investigate the radiosensitizing effect and underlying mechanisms of CPP on hypoxic A549 and H520 human non­small cell lung carcinoma cells. Cell viability, apoptosis and proliferation were determined using Cell Counting kit­8 assay, flow cytometry and colony formation assay, respectively. mRNA and protein expression levels were determined by reverse transcription­quantitative PCR and western blot analysis, respectively. The results suggested that CPP markedly inhibited the viability of hypoxic A549 and H520 cells. In response to combined treatment with CPP and radiation, hypoxic A549 and H520 cells exhibited enhanced apoptosis; in addition, cell proliferation was suppressed and the expression levels of hypoxia­inducible factor­1α, survivin and cleaved caspase­3 were modified. Furthermore, CPP in combination with radiation affected the mammalian target of rapamycin (mTOR)/Akt/phosphatidylinositol­4,5­bisphosphate 3­kinase (PI3K) pathway. These findings indicated that CPP may enhance the radiosensitivity of hypoxic A549 and H520 cells; this effect may be associated with inhibition of the mTOR/Akt/PI3K pathway. The potential radiosensitizing effects of CPP on hypoxic A549 and H520 cells suggested that CPP may be an effective target for treatment of non­small cell lung carcinoma.


Assuntos
Fagales/química , Extratos Vegetais/farmacologia , Polissacarídeos/farmacologia , Radiossensibilizantes/farmacologia , Células A549 , Biomarcadores , Carcinoma Pulmonar de Células não Pequenas , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Pulmonares , Modelos Biológicos , Fosfatidilinositol 3-Quinases/metabolismo , Extratos Vegetais/química , Polissacarídeos/química , Proteínas Proto-Oncogênicas c-akt/metabolismo , Tolerância a Radiação/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR
19.
Mar Pollut Bull ; 146: 76-84, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31426218

RESUMO

To assess the ecological health of the Chongming Dongtan Nature Reserve (CDNR), univariate and multimetric indices-AZTI's Marine Biotic Index (AMBI), multivariate AMBI (M-AMBI), abundance-biomass comparison curves, taxonomic diversity, Shannon-Wiener index (H') (log2), and Benthic Opportunistic Polychaetes Amphipods index (BOPA) - were used to translate the macrobenthic community into classifications of ecological health in 2016 and 2017. Based on the results of the various indicators, the overall habitat status of the CDNR ranged from good to high status. Sites 4 and 5, which fell in the remaining tidal flats following reclamation activities, were classified as disturbed, whereas the degree of disturbance at site 3 was low. The results indicate that the CDNR is under some form of human disturbance, which includes reclamation and animal (mainly cattle) grazing. H' (log2) and M-AMBI index may be more suitable for assessing ecological quality in intertidal zones, including the CDNR.


Assuntos
Conservação dos Recursos Hídricos , Monitoramento Ambiental/métodos , Invertebrados , Anfípodes , Animais , Organismos Aquáticos , Biodiversidade , Biomassa , Bovinos , China , Ecossistema , Invertebrados/classificação , Ilhas
20.
Fish Shellfish Immunol ; 93: 1028-1040, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31430559

RESUMO

Toll-like receptors (TLRs) are a category of pattern recognition receptors (PRRs), which recognize pathogen associated molecular patterns (PAMPs) and participate in the immune responses. We identified tlr5a, tlr5b, tlr9 and tlr21 from the genome of blunt snout bream (Megalobrama amblycephala). All four tlrs were constitutively expressed in all examined tissues. After an immune bacterial challenge with Aeromonas hydrophila, their expressionwas up-regulated in lymphoid organs and tissues. Recombinant eukaryotic plasmid pEGFP-N1 was transfected into the common carp (Cyprinus carpio) EPC (epithelioma papulosum cyprini) cells for the purpose of subcellular localization. pcDNA3.1(+) recombinant eukaryotic plasmid was used to investigate the effects of overexpression of tlrs on the expression of downstream interferon-associated immune factors. The four Tlrs were distributed in the cytoplasm of transfected cells and appeared as filamentous or reticular. The expression of irf3, irf7, isg15, mx1, pkr and viperin at 0, 6, 12, 18, 24, 36, 48 and 72 h post-transfection in transfected EPC cells was quantified by qPCR. Overexpression of tlrs upregulated the expression of viperin, isg15, irf3, irf7, mx1 and pkr (in that order of magnitude). We also cloned the following promoters of irfs: Irf1-p, irf2-p, irf6-p, irf7-p, irf8-p and irf9-p. Results of the dual luciferase reporter assay suggested that tlr5a, tlr5b and tlr9 enhanced the activities of irf7-p, while tlr5b enhanced the activities of irf1-p and irf7-p. This suggests that they all play a role in the innate immunity. The experiments also indicated that TLRs activate irf3 or irf7 signaling to induce IFN secretion and subsequent upregulation of IFN-stimulated genes. These results indicate that tlrs and irfs play an important immune role in response to A. hydrophila infection in blunt snout bream, and pave the way for further studies of immune mechanisms mediated by TLRs in fish.


Assuntos
Cyprinidae/genética , Cyprinidae/imunologia , Doenças dos Peixes/imunologia , Regulação da Expressão Gênica/imunologia , Imunidade Inata/genética , Receptores Toll-Like/genética , Receptores Toll-Like/imunologia , Aeromonas hydrophila/fisiologia , Animais , Sequência de Bases , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Perfilação da Expressão Gênica/veterinária , Infecções por Bactérias Gram-Negativas/imunologia , Infecções por Bactérias Gram-Negativas/veterinária
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