Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.847
Filtrar
1.
J Proteomics ; 211: 103578, 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31689562

RESUMO

Temozolomide (TMZ) is the first-line chemotherapeutic drug for glioblastoma treatment. It can induce O6-methylguanine DNA lesions, lead to prolonged G2-M arrest and ultimately cell death. However, the molecular response induced by TMZ has not been fully elucidated. In this study, by integrating quantitative proteomics and metabolomics, we identified protein and metabolite markers that correlate with TMZ treatment and discovered the protein-metabolite regulatory network. A total of 1782 proteins and 56 endogenous metabolites were significantly altered in the brain between sham and tumor groups, 38 metabolites markedly altered in plasma. After TMZ treatment, 251 proteins and 9 metabolites significantly changed in the brain, and 14 metabolites did in plasma. 35 proteins significantly altered by TMZ were further validated by parallel reaction monitoring (PRM) analysis. The multi-omics analysis revealed differential proteins and metabolites were involved in DNA replication, nucleotides degradation, cysteine biosynthesis, and other pathways. Adenosine, sarcosine and adenosine deaminase involved in multiple metabolic pathways may serve as potential biomarkers for TMZ treatment. This is the first report utilizing multi-omics analysis to investigate the global response of proteins and metabolites in glioma by TMZ treatment, and the data can provide a comprehensive insight to understand the mechanism of TMZ. SIGNIFICANCE: The study focused on integrating quantitative proteomics and endogenous metabolites profiling of the rat glioma brain in response to chemotherapeutic drug temozolomide treatment, which has not yet been reported. The results showed that the effect of temozolomide on glioma is significant, including DNA replication, nucleotides degradation, cysteine biosynthesis, and synaptogenesis signaling pathway. Our study can provide a comprehensive insight to screen potential targets and biomarkers of glioma as well as to elucidate the mechanism of temozolomide inhibiting tumor growth.

2.
J Nanosci Nanotechnol ; 20(2): 668-672, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31383061

RESUMO

Currently, optical probes with near-infrared (NIR) fluorescence are of great interest in chemical biology. In the present study, we designed and synthesized a novel NIR fluorescent probe, IR789. IR789 has high selectivity and sensitivity for living cells imaging. The stronger excitation and emission characteristics suggested its dominant optical properties over ICG. IR789 also showed a high affinity and inconspicuous cytotoxicity at the cellular level. The results of fluorescent image in living A549 cells (human lung adenocarcinoma epithelial cell line) further demonstrated its potential applications for biomedical diagnosis in biological systems utilization of nanotechnology.

3.
Nat Commun ; 10(1): 5121, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31719535

RESUMO

Both short and long sleep are associated with an adverse lipid profile, likely through different biological pathways. To elucidate the biology of sleep-associated adverse lipid profile, we conduct multi-ancestry genome-wide sleep-SNP interaction analyses on three lipid traits (HDL-c, LDL-c and triglycerides). In the total study sample (discovery + replication) of 126,926 individuals from 5 different ancestry groups, when considering either long or short total sleep time interactions in joint analyses, we identify 49 previously unreported lipid loci, and 10 additional previously unreported lipid loci in a restricted sample of European-ancestry cohorts. In addition, we identify new gene-sleep interactions for known lipid loci such as LPL and PCSK9. The previously unreported lipid loci have a modest explained variance in lipid levels: most notable, gene-short-sleep interactions explain 4.25% of the variance in triglyceride level. Collectively, these findings contribute to our understanding of the biological mechanisms involved in sleep-associated adverse lipid profiles.

4.
J Comp Physiol B ; 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31729534

RESUMO

Whether hibernation accelerates or suppresses autophagy is still unknown. In the current study, we examined changes in autophagy in oxidative soleus (SOL) muscle in summer active (SA), pre-hibernation (PRE), torpor (TOR), interbout arousal (IBA), and post-hibernation groups of Daurian ground squirrels (Spermophilus dauricus). Here, the SOL muscle showed no significant atrophy during hibernation in regard to muscle wet weight, fiber cross-sectional area, or MuRF1 protein level. Autophagy-related proteins beclin1 and Atg7 increased significantly, whereas LC3-II decreased significantly in the PRE group compared with the SA group. However, neither the expression nor activity of cathepsin L showed any differences between the SA and PRE groups. In addition, beclin1, LC3-II, and the LC3-II/LC3-I ratio increased, p62 decreased, LC3 puncta increased, p62 puncta decreased, and cathepsin L activity increased in the TOR group compared with the PRE group. In contrast, beclin1, LC3-II, and the LC3-II/LC3-I ratio decreased, p62 increased, LC3 puncta decreased, p62 puncta increased, and cathepsin L activity declined in the IBA group compared with the TOR group. Moreover, the phosphorylation of Akt (Ser473) and mTOR (Ser2448) changed significantly during hibernation and showed an inverse relationship with autophagy changes. In conclusion, autophagy proteins displayed periodic oscillation in the torpor-arousal cycle, which may be advantageous in maintaining SOL muscle mass during the entire hibernation period. Furthermore, the Akt-mTOR signaling was decreased in TOR and increased in IBA group in the SOL muscle of Daurian ground squirrels during hibernation.

5.
Cancer Sci ; 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31742824

RESUMO

Identification of deleterious variants in HBOC susceptibility genes allows for increased clinical surveillance and early detection, and could predict the response to PARP inhibitor in patient with advanced ovarian carcinomas. To determine the prevalence and clinical prediction factors for hereditary breast and ovarian carcinoma syndrome, 882 selected individuals underwent multigene panel testing for hereditary breast and ovarian cancer (HBOC) risk assessment at the period from January 2015 to March 2018. Overall, 176 deleterious mutations were observed in 19.50% (n = 172) individuals. 26 of 176 mutations were not previously as well as archived in public database. Among patients with ovarian cancer, 115 deleterious mutations were identified in 429 patients (48.6%) with significant enrichment for a family history of breast or ovarian cancer syndrome (p < 0.05). In breast cancer subgroup, 31 deleterious mutations were identified in 261 patients. Besides BRCA1 (8; 25.8%) and BRCA2 (11; 35.5%), most occurred genes, an additional 12 deleterious mutations (38.7%) were found in 7 other susceptibility genes. Higher mutation incidence (57.9%) was observed in subjects with histories of breast and ovarian cancer. Our results highlighted the genetic heterogeneity of HBOC and the efficiency of multigene panel in performing risk assessment.

6.
J Cell Mol Med ; 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31667932

RESUMO

Macrophages play key roles in the secondary injury stage of spinal cord injury (SCI). M1 macrophages occupy the lesion area and secrete high levels of inflammatory factors that hinder lesion repair, and M2 macrophages can secrete neurotrophic factors and promote axonal regeneration. The regulation of macrophage secretion after SCI is critical for injury repair. Low-level laser therapy (810-nm) (LLLT) can boost functional rehabilitation in rats after SCI; however, the mechanisms remain unclear. To explore this issue, we established an in vitro model of low-level laser irradiation of M1 macrophages, and the effects of LLLT on M1 macrophage polarization and neurotrophic factor secretion and the related mechanisms were investigated. The results showed that LLLT irradiation decreased the expression of M1 macrophage-specific markers, and increased the expression of M2 macrophage-specific markers. Through forward and reverse experiments, we verified that LLLT can promote the secretion of various neurotrophic factors by activating the PKA-CREB pathway in macrophages and finally promote the regeneration of axons. Accordingly, LLLT may be an effective therapeutic approach for SCI with clinical application prospects.

7.
Ophthalmol Retina ; 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31669329

RESUMO

PURPOSE: To evaluate spectral-domain (SD)-OCT features associated with baseline vision and visual outcomes in the prospective, multicenter Study Evaluating Dosing Regimens for Treatment with Intravitreal Ranibizumab Injections in Subjects with Macular Edema following Retinal Vein Occlusion (SHORE). DESIGN: Post hoc analysis of prospective clinical trial data. PARTICIPANTS: Two hundred two participants in the 15-month, phase 4 SHORE study comparing monthly versus pro re nata ranibizumab after 7 monthly doses in eyes with retinal vein occlusion (RVO) with macular edema. METHODS: Baseline SD-OCT images were assessed for (1) central subfield thickness (CST); (2) presence of vitreomacular adhesion, vitreomacular traction, or epiretinal membrane; (3) presence, location, and amount of intraretinal fluid or subretinal fluid (SRF); (4) presence, location, and amount of hyperreflective foci (HF); (5) disorganization of retinal inner layers (DRIL); and (6) disruption of external limiting membrane (ELM), ellipsoid zone (EZ), and interdigitation zone (IZ). Univariate and multivariate regression analyses were performed to evaluate the association of these features with baseline best-corrected visual acuity (BCVA) and change in BCVA after 7 monthly ranibizumab injections. MAIN OUTCOME MEASURES: Association of SD-OCT features with baseline BCVA and change in BCVA after 7 monthly ranibizumab injections. RESULTS: Before therapy, worse baseline BCVA was associated with ERM presence (P = 0.0045), thicker SRF (P = 0.0006), larger intraretinal cysts (P = 0.0015), and higher percentage of DRIL (P < 0.0001), percentage of ELM disruption (P < 0.0001), percentage of EZ disruption (P = 0.0003), and percentage of IZ disruption (P = 0.0018). In multivariate models, only percentage of ELM disruption independently impacted baseline BCVA (P < 0.0001). After 7 monthly ranibizumab injections, mean BCVA improved by 18.3±12.6 Early Treatment Diabetic Retinopathy Study letters in treated eyes. The only factors independently associated with BCVA gain after 7 monthly ranibizumab treatments were younger age (P < 0.0001) and worse baseline BCVA (P < 0.0001). CONCLUSIONS: Although SD-OCT features may be associated with presenting vision in eyes with macular edema and RVO, most eyes treated with ranibizumab achieve substantial vision gains, and only older age and better baseline BCVA limited visual improvements.

8.
J Biophotonics ; 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31670897

RESUMO

AIM: Previous studies on spinal cord injury (SCI) have confirmed that percutaneous photobiomodulation (PBM) therapy can ameliorate immunoinflammatory responses at sites of injury, accelerate nerve regeneration, suppress glial scar formation, and promote the subsequent recovery of locomotor function. The current study was performed to evaluate a large-animal model employing implanted optical fibers to accurately irradiate targeted spinal segments. The method's feasibility and irradiation parameters that do not cause phototoxic reaction were determined, and the methodology of irradiating the spinal cord with near-infrared light was investigated in detail. METHODS: A diffusing optical fiber was implanted above the T9 spinal cord of Bama miniature pigs and used to transfer near-infrared light (810 nm) onto the spinal cord surface. After daily irradiation with 200, 300, 500, or 1000 mW for 14 days, both sides of the irradiated area of the spinal cord were assessed for temperature changes. The condition of the spinal cord and the position of optical fiber were investigated by magnetic resonance imaging (MRI), and different parameters indicating temperature increases or phototoxicity were measured on the normal spinal cord surface due to light irradiation (i.e., heat shock responses, inflammatory reactions, and neuronal apoptosis), and the animals' lower-limb neurological function and gait were assessed during the irradiation process. RESULTS: The implanted device was stable inside the freely moving animals, and light energy could be directly projected onto the spinal cord surface. The screening of different irradiation parameters preliminary showed that direct irradiation onto the spinal cord surface at 200 and 300 mW did not significantly increase the temperature, stress responses, inflammatory reactions and neural apoptosis, whereas irradiation at 500 mW slightly increased these parameters, and irradiation at 1000 mW induced a significant temperature increase, heat shock, inflammation and apoptosis responses. HE staining of spinal cord tissue sections did not reveal any significant structural changes of the tissues compared to the control group, and the neurological function and gait of all irradiated animals were normal. CONCLUSION: In this study, we established an in-vivo optical fiber implantation method, which might be safe and stable and could be used to directly project light energy onto the spinal cord surface. This study might provide a new perspective for clinical applications of PBM in acute SCI. This article is protected by copyright. All rights reserved.

9.
Appl Opt ; 58(27): 7416-7423, 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31674390

RESUMO

The intracellular dynamics of onion epidermal cells during the dehydration process is observed by holographic microscopy. Both the nucleus and cytoplasm are accurately revealed by quantitative phase imaging while dehydration takes place. Indeed, we notice that the contrast of phase images increases with the decrease in cellular water content. We foresee that such a dehydrating process can be effective for improving phase contrast, thus permitting better imaging of plant cells with the scope of learning more about cellular dynamics and related phenomena. Exploiting this concept, we observe intracellular cytoplasmic circulation and transport of biological material.

10.
Int J Numer Method Biomed Eng ; : e3273, 2019 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-31680466

RESUMO

Heart Failure (HF) refers to the heart's inability to pump sufficient blood to maintain the body's needs, which has a very serious impact on human health. In recent years, the prevalence of heart failure has remained high. This paper proposes a multi-view ensemble learning algorithm based on empirical kernel mapping called MVE-EK, which predicts the mortality of patient through hospital records. Multi-view ensemble learning can take advantage of the consistency and complementarity of different views. The MVEEK first divides the patient's features into multiple views. Then divides the samples of each view to multiple subsets through under sampling, which can reduce the imbalance rate of the original dataset and obtain some relatively balanced subsets. Each subset is mapped into kernel space by empirical kernel mapping, which can map samples from linearly inseparable spaces to linearly separable spaces. Finally, the multi-view ensemble learning is performed by the designed loss of acquaintance between views. The effectiveness of the algorithm is verified on the three datasets of HF patient in the real world. The performance of the algorithm is better than other comparison algorithms. The datasets are collected from Shanghai Shuguang Hospital and involve 10,203 hospitalization records for 4,682 heart failure patients between March 2009 and April 2016. The prediction information provided by the algorithm can assist the clinician in providing a more personalized treatment plan for patients with heart failure.

11.
Acta Pharmacol Sin ; 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31705124

RESUMO

Stem cell therapy represents the potential alternative effective strategy for some diseases that lack effective treatment currently. Correspondingly, it is crucial to establish high-sensitive and reliable quantification assay for tracing exogenous cell migration. In the present study, we first used both bioluminescence imaging (BLI) indirect labeling (human norepinephrine transporter-luciferase reporter system) and 89zirconium (89Zr)-hNSCs direct labeling combined with positron emission tomography/computer tomography (PET/CT) system for tracking human neural stem cells (hNSCs) migration into the brain via nasal administration in preclinical study. But the above two methods failed to give the biodistribution profile due to their low sensitivity. Considering its superior sensitivity and absolute quantitation capability, we developed and validated the droplet digital PCR (ddPCR) targeting species-specific gene in frozen and paraffin sections, slices, and whole blood with the sensitivity of 100-200 hNSCs. Accurate and high throughput quantification could be performed using ddPCR with the coefficient of variation (CVs) of lower quality control (LQC) below 30%. In combination with immunohistochemistry and ddPCR, we confirmed the migration of hNSCs into the brain via nasal administration, which supported the efficacy of hNSCs in MPTP-treated mice, an animal model of Parkinson's disease. In conclusion, the present study is the first to report the application of ddPCR in the pharmacokinetics profile description of tracking of hNSCs in preclinical studies.

12.
Zool Res ; : 1-10, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31709786

RESUMO

Molecular studies on donkey mitochondrial sequences have clearly defined two distinct maternal lineages involved in domestication. However, domestication histories of these two lineages remain enigmatic. We therefore compared several population characteristics between these two lineages based on global sampling, which included 171 sequences obtained in this study (including Middle Asian, East Asian, and African samples) plus 536 published sequences (including European, Asian, and African samples). The two lineages were clearly separated from each other based on whole mitochondrial genomes and partial non-coding displacement loop (D-loop) sequences, respectively. The Clade I lineage experienced an increase in population size more than 8 000 years ago and shows a complex haplotype network. In contrast, the population size of the Clade II lineage has remained relatively constant, with a simpler haplotype network. Although the distribution of the two lineages was almost equal across the Eurasian mainland, they still presented discernible but complex geographic bias in most parts of Africa, which are known as their domestication sites. Donkeys from sub-Saharan Africa tended to descend from the Clade I lineage, whereas the Clade II lineage was dominant along the East and North coasts of Africa. Furthermore, the migration routes inferred from diversity decay suggested different expansion across China between the two lineages. Altogether, these differences indicated non-simultaneous domestication of the two lineages, which was possibly influenced by the response of pastoralists to the desertification of the Sahara and by the social expansion and trade of ancient humans in Northeast Africa, respectively.

13.
Prenat Diagn ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31713898

RESUMO

OBJECTIVE: To determine factors associated to poor outcomes and the need for surgical treatment in neonates with meconium peritonitis (MP). METHODS: We evaluated the association between prenatal ultrasound features, maternal characteristics, and the likelihood of surgery, mortality, and serious morbidity in 49 neonates with a prenatal diagnosis of MP, who were born in Guangzhou Women and Children's Medical Center between January 2011 and December 2016. RESULTS: Thirty of 49 neonates (61.2%) required surgical treatment and 17 (34.7%) had a poor outcome. Independent predictors of need for surgical treatment were polyhydramnios, maternal intrahepatic cholestasis of pregnancy (associated with lower risk) and persistence of peritoneal fluid. The model correctly predicted 70.0% of the neonates who required surgery (at a 10% false positive rate; AUC: 0.86[95%CI: 0.75-0.97]). For poor outcomes, independent predictors were low gestational age at birth, persistence of peritoneal fluid and polyhydramnios. For the latter, the model only achieved a detection rate of 52.9% (10% false positive rate, AUC: 0.82 [95%CI: 0.70-0.94]). CONCLUSIONS: A combination of prenatal ultrasound features and maternal characteristics correctly predicted 70.0% the need for neonatal surgery. Prediction of poor outcome based prenatal ultrasound features and gestational age did not perform well.

14.
J Pharm Pract ; : 897190019885274, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31694447

RESUMO

OBJECTIVES: To evaluate and compare students' ability to perform in each area of the subjective, objective, assessment, and plan (SOAP) note during advanced pharmacy practice experiences (APPEs) within an academic year. This study also aimed to compare the quality of SOAP notes between semesters: summer (1-3 rotation blocks), fall (4-6 rotation blocks), and spring (7-9 rotation blocks). METHODS: During internal medicine and acute-care APPEs, students were required to submit a minimum of 2 SOAP notes. Each SOAP note was assessed by a full-time faculty member at a College of Pharmacy. Students were rated on the ability to perform in each area of the SOAP note using a rubric with a scale of 1 to 5 (1 = unacceptable/needs significant improvement, 5 = exemplary). This study was granted exempt approval by the Long Island University institutional review board. RESULTS: Quality of the SOAP note summer versus fall versus spring rotations: Thirty-four SOAP notes were assessed during the summer, 48 SOAP notes were assessed during the fall, and 46 SOAP notes were assessed during the spring. Students performed similarly regardless of the semester they took for "subjective/objective, assess, and plan." All P values were nonstatistically significant. Performance on SOAP note #1 versus SOAP note # 2: On overall rubrics for SOAP notes 1 versus SOAP notes 2, students did better on SOAP notes 2 after feedback, and an opportunity to improve was provided. There were statistically significant differences on all areas of SOAP note "subjective/objective, assess, and plan." Conclusion: Overall, students performed adequately on the SOAP note activity during APPE rotations. Students performed similarly regardless of the semester/time when students took the APPEs during an academic year.

15.
Biomater Sci ; 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31687671

RESUMO

Chemotherapy is a dominant treatment modality for different types and stages of cancer. However, hypoxia is one of the undesirable limitations of chemotherapy, which reduces the therapeutic efficiency in cancer treatment, ultimately leading to failure of the treatment. Herein, an ideal chemosensitization system capable of attenuating the tumor hypoxia microenvironment and enhancing chemotherapy effects in tumors was designed. This system (designated as the RA/RX Liposome) uses for the first time a pH-sensitive liposome to co-deliver cyclopeptide RA-V as chemotherapeutic drugs and antisense oligonucleotides as HIF-1α inhibitors (RX-0047) for attenuating tumor hypoxia, as well as a caspase-8 activation probe for therapeutic self-monitoring. After modification with death receptor 5-specific antibodies (anti-DR5) on the surface of the liposome, the RA/RX Liposome can successfully deliver components targeting colon tumors in vivo. This work should synergistically enhance the therapeutic effects of the treatment by successfully down-regulating HIF-1α expression against tumor hypoxia during the RA-V-induced apoptotic process. More importantly, the RA/RX Liposome can be precisely applied for therapeutic self-monitoring with the light-up fluorescence of the caspase-8 probe.

16.
Phys Chem Chem Phys ; 21(45): 25276-25289, 2019 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-31701109

RESUMO

As a member of the bromodomain and extra terminal domain (BET) protein family, bromodomain-containing protein 4 (BRD4) is an epigenetic reader and can recognize acetylated lysine residues in histones. BRD4 has been regarded as an essential drug target for cancers, inflammatory diseases and acute heart failure, and therefore the discovery of potent BRD4 inhibitors with novel scaffolds is highly desirable. In this study, the crystalline water molecules in BRD4 involved in ligand binding were analyzed first, and the simulation results suggest that several conserved crystalline water molecules are quite essential to keep the stability of the crystalline water network and therefore they need to be reserved in structure-based drug design. Then, a docking-based virtual screening workflow with the consideration of the conserved crystalline water network in the binding pocket was utilized to identify the potential inhibitors of BRD4. The in vitro fluorescence resonance energy transfer (HTRF) binding assay illustrates that 4 hits have good inhibitory activity against BRD4 in the micromolar regime, including three compounds with IC50 values below 5 µM and one below 1 µM (0.37 µM). The structural analysis demonstrates that three active compounds possess novel scaffolds. Moreover, the interaction patterns between the hits and BRD4 were characterized by molecular dynamics simulations and binding free energy calculations, and then several suggestions for the further optimization of these hits were proposed.

17.
Artigo em Inglês | MEDLINE | ID: mdl-31701743

RESUMO

The ability to generate stressed semiconductor particles is of great importance in the development of tunable semiconductor and photonic devices. However, existing methods including both bottom-up synthesis and top-down fabrication for producing semiconductor particles are inherently free of stress effects. Here, we report a simple approach to generate controllable stress effects on both encapsulated and free-standing semiconductor particles using laser-structured in-fiber materials engineering. The physical mechanism of thermally induced in-fiber built-in stress is investigated, and the feasibility of precisely tuning the stress state during the particle formation is experimentally demonstrated by controlling the laser treatment. Gigapascal-level built-in stress, which is a sufficiently strong stimulus to enable inelastic deformations on the fabricated semiconductor particles, has been achieved via this approach. Both encapsulated and free-standing stressed semiconductor particles are generated for a wide range of in-fiber and out-fiber optoelectronic and biomedical applications.

18.
Nat Commun ; 10(1): 5206, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31729394

RESUMO

The ability to manipulate in-fibre particles is of technological and scientific significance, yet particle manipulation inside solid environment remains fundamentally challenging. Here we show an accurately controlled, non-contact, size- and material-independent method for manipulating in-fibre particles based on laser-induced thermocapillary convection. The laser liquefaction process transforms the fibre from a solid media into an ideal fluid environment and triggers the in-fibre thermocapillary convection. In-fibre particles, with diameter from submicron to hundreds of microns, can be migrated toward the designated position. The number of particles being migrated, the particle migration velocity and direction can be precisely controlled. As a proof-of-concept, the laser-induced flow currents lead to the migration-to-contact of dislocated in-fibre p- and n-type semiconductor particles and the forming of dual-particle p-n homo- and heterojunction directly in a fibre. This approach not only enables in-fibre device assembly to achieve multi-component fibre devices, but also provide fundamental insight for in-solid particle manipulation.

19.
J Viral Hepat ; 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31755220

RESUMO

Antiviral therapy has been shown to improve the prognosis of hepatitis B virus (HBV) DNA-positive hepatocellular carcinoma (HCC) after radical treatment, but antiviral treatments require further optimization. This study aimed to evaluate the efficacies of different antiviral strategies with HCC patients after hepatectomy/ablation. This prospective, randomized, controlled, and multi-center trial enrolled HBV DNA-positive primary HCC patients after hepatectomy/ablation between January 2007 and January 2009. Patients were divided into four groups: early-combination (entecavir plus Peg-interferon [IFN]α-2a co-administration during year 1); late-combination (addition of Peg-IFNα-2a for 48 weeks after 1 year of entecavir); nucleos(t)ide analogue[NA] monotherapy; and non-antiviral treatment. Primary endpoints included recurrence-free survival and overall survival. A total of 447 patients were enrolled. The 2-year and 8-year recurrence free survival and 8-year overall survival rates were significantly higher in the early-combination group than in the other two antiviral groups (P<0.05). After 48 weeks treatment, more patients achieved an HBsAg reduction >1500 IU/ml and the mean HBsAg level was significantly lower in the early-combination group compared with the late-combination and NA monotherapy groups (P<0.05). Multivariate analysis showed that early-combination therapy and a reduction in HBsAg by >1500 IU/mL after 48 weeks of therapy correlated with reduced mortality and disease recurrence. Early introduction of combination antiviral treatment may represent a more effective therapeutic strategy for patients with HBV DNA-positive HCC after hepatectomy/ablation. A reduction in HBsAg by >1500 IU/mL after 48 weeks treatment is associated with reduced mortality and disease recurrence of HBV DNA-positive HCC patients after hepatectomy/ablation.

20.
Thorac Cancer ; 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31755241

RESUMO

BACKGROUND: The roles of p62-Keap1-Nrf2 pathway in the radioresistance of esophageal squamous cell carcinoma (ESCC) have not yet been revealed. This study aimed to clarify the expression and correlation of p-p62 and nuclear Nrf2 and their association with radioresistance in ESCC. METHODS: This study included 164 cases of inoperable locally advanced ESCC. All patients received concurrent chemoradiotherapy (CCRT). Immunohistochemical staining was used to detect the expression of p-p62 and nuclear Nrf2. The results were analyzed independently by two pathologists. RESULTS: There was no significant relationship between p-p62 or nuclear Nrf2 and patients' clinical characteristics. Compared to patients with low expression of p-p62, patients with high expression of p-p62 showed lower objective response rate (ORR). Similarly, patients with high expression of nuclear Nrf2 exhibited lower ORR compared to those with low expression of nuclear Nrf2. The expression of p-p62 was positively correlated with that of nuclear Nrf2. Moreover, the correlation coefficient between them was higher among patients showing no response to CCRT. Univariate analysis revealed that higher expression of p-p62 or nuclear Nrf2 was significantly associated with poorer PFS and OS. Multivariate analysis indicated that the expression of nuclear Nrf2 and treatment response were independent prognostic factors for PFS. Sex, treatment response, expression of p-p62 and nuclear Nrf2 were independent prognostic factors for OS. CONCLUSION: Higher expression of p-p62 and nuclear Nrf2 are associated with lower ORR as well as poorer prognosis, which indicates that p62-Keap1-Nrf2 pathway might play an essential role in the radioresistance of ESCC.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA