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1.
Food Chem ; 304: 125383, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31479997

RESUMO

An aqueous two-phase system was used in conjunction with ultrasonic cell disruption to extract and separate solanine (mainly solasonine and solamargine) and Solanum nigrum polysaccharide from Solanum nigrum unripe fruit. The optimized conditions of the present study were determined by a single-factor experiment and a multifactor experiment. The concentration of ethanol was set at 60% and the duration of the ultrasonic cell disruption extraction was 50 min. In the ethanol-K2CO3 aqueous two-phase separation system, the concentration of ethanol was 36%, the concentration of K2CO3 was 0.21 mg·mL-1, and the temperature was 15 °C. The solasonine and solamargine were determined by high-performance liquid chromatography, and the Solanum nigrum polysaccharide was determined by an ultraviolet-visible spectrophotometer in accordance with the phenol-sulfuric acid method. xUnder optimized conditions, the average extraction efficiencies of solasonine, solamargine and Solanum nigrum polysaccharide were 95.86%, 95.95% and 96.95%, respectively, and the average separation efficiencies of solasonine, solamargine and Solanum nigrum polysaccharide were 2.07 mg·g-1, 2.05 mg·g-1 and 8.15 mg·g-1, respectively.

2.
J Cell Biochem ; 2019 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-31680309

RESUMO

Dysregulation of long noncoding RNAs (lncRNAs) has been found in a large number of human cancers, including colon cancer. Therefore, the implementation of potential lncRNAs biomarkers with prognostic prediction value are very much essential. GSE39582 data set was downloaded from database of Gene Expression Omnibus. Re-annotation analysis of lncRNA expression profiles was performed by NetAffx annotation files. Univariate and multivariate Cox proportional analyses helped select prognostic lncRNAs. Algorithm of random survival forest-variable hunting (RSF-VH) together with stepwise multivariate Cox proportional analysis were performed to establish lncRNA signature. The log-rank test was carried out to analyze and compare the Kaplan-Meier survival curves of patients' overall survival (OS). Receiver operating characteristic (ROC) analysis was used for comparing the survival prediction regarding its specificity and sensitivity based on lncRNA risk score, followed by calculating the values of area under the curve (AUC). The single-sample GSEA (ssGSEA) analysis was used to describe biological functions associated with this signature. Finally, to determine the robustness of this model, we used the validation sets including GSE17536 and The Cancer Genome Atlas data set. After re-annotation analysis of lncRNAs, a total of 14 lncRNA probes were obtained by univariate and multivariate Cox proportional analysis. Then, the RSF-VH algorithm and stepwise multivariate Cox analysis helped to build a five-lncRNA prognostic signature for colon cancer. The patients in group with high risk showed an obviously shorter survival time compared with patients in group with low risk with AUC of 0.75. In addition, the five-lncRNA signature can be used to independently predict the survival of patients with colon cancer. The ssGSEA analysis revealed that pathways such as extracellular matrix-receptor interaction was activated with an increase in risk score. These findings determined the strong power of prognostic prediction value of this five-lncRNA signature for colon cancer.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31689217

RESUMO

Recent studies of imbalanced data classification have shown that the imbalance ratio (IR) is not the only cause of performance loss in a classifier, as other data factors, such as small disjuncts, noise, and overlapping, can also make the problem difficult. The relationship between the IR and other data factors has been demonstrated, but to the best of our knowledge, there is no measurement of the extent to which class imbalance influences the classification performance of imbalanced data. In addition, it is also unknown which data factor serves as the main barrier for classification in a data set. In this article, we focus on the Bayes optimal classifier and examine the influence of class imbalance from a theoretical perspective. We propose an instance measure called the Individual Bayes Imbalance Impact Index (IBI³) and a data measure called the Bayes Imbalance Impact Index (BI³). IBI³ and BI³ reflect the extent of influence using only the imbalance factor, in terms of each minority class sample and the whole data set, respectively. Therefore, IBI³ can be used as an instance complexity measure of imbalance and BI³ as a criterion to demonstrate the degree to which imbalance deteriorates the classification of a data set. We can, therefore, use BI³ to access whether it is worth using imbalance recovery methods, such as sampling or cost-sensitive methods, to recover the performance loss of a classifier. The experiments show that IBI³ is highly consistent with the increase of the prediction score obtained by the imbalance recovery methods and that BI³ is highly consistent with the improvement in the F1 score obtained by the imbalance recovery methods on both synthetic and real benchmark data sets.

4.
J Pharm Biomed Anal ; : 112924, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31672580

RESUMO

A rapid and sensitive ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was applied to investigate the permeability characteristics and transport mechanism of trihexyphenidyl hydrochloride (TH) in D-hanks with the Caco-2 cells model. Analytes were separated using an Zorbax Extend-Agilent C18 (1.8 µm, 4.6 × 30 mm) column following a simple methanol precipitation treatment. The mobile phase consisted of methanol and water containing 0.1% formic acid, and the total gradient program time was 1.5 min. Method validation results showed TH was linear in 2-500 ng/mL (r2 > 0.99), and the lower limit of quantification (LLOQ) was 2 µg/mL. The intra-run and inter-run precision (coefficient of variation, CV) was within 2.80%, and the accuracy (relative error, RE) was within ±11.10%. Stability of TH was evaluated in different storage conditions, including short-term I-III, long-term I-III, 2 and 4 h in the artificial gastrointestinal tract, respectively. There was no obvious interference between TH and internal standards (IS). With the established Caco-2 monolayer permeability model, Papp(AB) of TH was calculated as 46.29 ±â€¯8.31 × 10-6 cm/s, and the efflux ratio (ER) value was calculated as 0.22, indicating a high permeability character of TH. The transmembrane transport of TH followed the concentration-dependent, temperature-independent, and energy-free manner. Collectively, these characteristics indicate that TH is a highly permeable drug and the transport mechanism is mainly via passive diffusion.

5.
Appl Opt ; 58(27): 7436-7442, 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31674393

RESUMO

A scanning interferometry system based on near-infrared low-coherence interferometry by using a superluminescent diode (SLD) as the light source is presented. The system cannot only measure the surface profile of doped double-sided polished silicon but also measure its optical thickness and refractive index. The measurement system uses near-infrared CCD to detect interferometric light in the near infrared, based on the Michelson interference principle. SLD has low temporal and high spatial coherence and high penetration to doped silicon wafers; thus, higher visibility can be obtained when measuring the rear side. Meanwhile, the optical thickness measured by low coherent scanning interference is compared with the optical thickness obtained by spectrally resolved interferometry to verify the accuracy of the system. Due to the periodic characteristics of interference fringes, the coherence length of the narrowband light source is usually greater than the path length difference of the interferometer. It gives the measurement a phase ambiguity of 2π, which may severely limit the application of the measurement. However, the short coherent length SLD light source used in the project can avoid 2π phase ambiguity problems. Besides, this system can perform full scanning in a larger step and achieve rapid on-line measurement of the target surface.

6.
Eur J Clin Pharmacol ; 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31677118

RESUMO

PURPOSE: Our aim was to evaluate the influence of genetic polymorphisms involved in the metabolism and transportation of deferasirox on deferasirox pharmacokinetics in the Chinese population. METHODS: Thirty-eight healthy Chinese subjects were administered with a single dose of 20 mg kg-1 deferasirox. Allelic discriminations for eight single-nucleotide polymorphisms (SNPs) in UDP-glucuronosyltransferase 1A1, 1A3 (UGT1A1, UGT1A3), multidrug resistance protein 2 (MRP2, ABCC2), and breast cancer resistance protein (BCRP, ABCG2) were performed. The concentrations of deferasirox in the plasma were determined by UPLC-MS/MS. RESULTS: Subjects carrying ABCC2 c.-24 T allele had a 65% higher clearance (CL/F) and 42% lower area under the concentration-time curve from 0 to 72 h (AUC0-72h) as compared with non-carriers (P = 0.008, P = 0.011, respectively). ABCC2 c.-24 T was also associated with 59% shorter half-life (T1/2) and 17% shorter mean residence time (MRT) (P = 0.030, P = 0.014, respectively). ABCC2 1249A was associated with a marginal increase in deferasirox Cmax (P = 0.07). Genetic polymorphisms of UGT1A1, UGT1A3, and ABCG2 did not significantly influence the pharmacokinetics of deferasirox. Subjects with UGT1A1 211GG-(-1352)CC-(-3156)GG haplotype had higher AUC0-72h than others. Since only two subjects were recruited in the GG-CC-GG group, further confirmative studies were warranted. CONCLUSIONS: ABCC2 c.-24 C>T was associated with the pharmacokinetic variability of deferasirox in Chinese subjects. This study revealed an important role of MRP2 in the pharmacokinetics of deferasirox and drew attention to drug combination with MRP2 inhibitors like cyclosporine and methotrexate in deferasirox therapy.

7.
J Pharm Pharmacol ; 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31730290

RESUMO

OBJECTIVE: Pulmonary delivery is an effective way to improve the bioavailability of drugs with extensive metabolism. This research was designed to study the different pharmacokinetic behaviours of small molecule drug after pulmonary delivery and intragastric (i.g) administration. METHODS: Raloxifene, a selective estrogen receptor modulator with low oral bioavailability (~2%), was chosen as the model drug. Studies were conducted systematically in rats, including plasma pharmacokinetics, excretion, tissue distribution and metabolism. KEY FINDINGS: Results showed that raloxifene solution dosed by intratracheal (i.t) administration exhibited relatively quick plasma elimination (t1/2  = 1.78 ± 0.14 h) and undetected absorption process, which was similar with intravenous injection. Compared with i.g administration, the bioavailability increased by 58 times, but the major route of excretion remained faecal excretion. Drug concentration on the bone and the target efficiency were improved by 49.6 times and five times, respectively. Benefited from quick elimination in the lung, chronic toxicity might be ignored. CONCLUSIONS: Pulmonary administration improved the bioavailability of raloxifene and further increased the distribution on the target organ (bone), with no obvious impact on its excretory pattern.

8.
Nat Commun ; 10(1): 5099, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31704930

RESUMO

High strength and high ductility are often mutually exclusive properties for structural metallic materials. This is particularly important for aluminum (Al)-based alloys which are widely commercially employed. Here, we introduce a hierarchical nanostructured Al alloy with a structure of Al nanograins surrounded by nano-sized metallic glass (MG) shells. It achieves an ultrahigh yield strength of 1.2 GPa in tension (1.7 GPa in compression) along with 15% plasticity in tension (over 70% in compression). The nano-sized MG phase facilitates such ultrahigh strength by impeding dislocation gliding from one nanograin to another, while continuous generation-movement-annihilation of dislocations in the Al nanograins and the flow behavior of the nano-sized MG phase result in increased plasticity. This plastic deformation mechanism is also an efficient way to decrease grain size to sub-10 nm size for low melting temperature metals like Al, making this structural design one solution to the strength-plasticity trade-off.

9.
Nanomedicine ; 23: 102095, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31669856

RESUMO

Recent studies have indicated that multidrug resistance (MDR) can significantly limit the effects of conventional chemotherapy. In this study, PT (Pachymic acid and dehydrotumulosic acid) are the two major triterpenoid components purified and identified in P. cocos. A liposomal co-delivery system encapsulating doxorubicin (DOX) and PT was prepared. Notably, the mechanism of PT reversed P-glycoprotein (P-gp) mediated MDR mainly relied on the inhibition of the P-gp function, which further decreased the levels of P-gp and caveolin-1 proteins. In drug-resistant MCF cells, co-administration with 5 µg/ml PT significantly enhanced sensitivity of DOX. Finally, liposome-mediated co-delivery with PT significantly improved the anti-tumor effect of DOX in tumor-bearing mice when compared to other single therapy groups. In conclusion, this study showed for the first time that DOX and PT act synergistically as an "all-in-one" treatment to reverse MDR during tumor treatment and, thus, should be studied further for a wide range of anti-cancer applications.

10.
Cornea ; 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31714404

RESUMO

PURPOSE: To test the hypothesis that pterygium presents with both refractive and anatomical changes, especially short axial length. METHODS: A retrospective, hospital-based cross-sectional study included 521 eyes from 521 patients who were enrolled through a community survey by Shanghai Heping Eye Hospital was conducted. Patients with primary pterygium in at least 1 eye were considered the pterygium group, and those with normal eyes were considered the nonpterygium group. The prevalence and length of pterygium, refractive characteristics including spherical power, astigmatism, corneal curvature, and anatomical parameters including axial length, anterior chamber depth, endothelial cell density, and corneal thickness were compared between groups. RESULTS: Five hundred twenty-one eyes of 521 patients (214 men and 307 women) with a mean age of 70.5 ± 7.6 years were included in the study. The prevalence of hyperopia (81.6%, 65.1%, P = 0.001), axial length (23.1 ± 1.2 mm, 24.2 ± 2.4 mm, P < 0.001), anterior chamber depth (2.9 ± 0.3 cm, 3.1 ± 0.4 cm, P = 0.001), flat K value (42.94 ± 2.16 diopters, 43.73 ± 1.48 diopters, P = 0.002), Kmax (51.13 ± 7.74 diopters, 47.49 ± 5.62 diopters, P < 0.001), and spherical power (0.97 ± 2.40 diopters, -0.82 ± 4.40 diopters, P < 0.001) were statistically different between the pterygium and nonpterygium groups. Age (r = -0.21, P = 0.025), corneal astigmatism (r = -0.41, P < 0.001), flat K value (r = -0.39, P < 0.001), and endothelial cell density (r = -0.33, P = 0.001) were all negatively correlated with the length of pterygium. The prevalence of pterygium and severe pterygium over 3 mm were statistically different according to the severity of hyperopia (P < 0.001) and axial length (P < 0.001). Stratified χ analysis showed that axial length, rather than hyperopia, was a related factor to pterygium (odds ratio = 5.23, 95% confidence interval: 2.50-10.93). CONCLUSIONS: We conclude from our study that the prevalence of pterygium is related to small eye size. SDF-1/CXCR4 signaling may play a vital role in pterygium and shorter axial length. Further study focused on SDF-1/CXCR4 signaling will be needed.

11.
Emerg Microbes Infect ; 8(1): 1658-1667, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31718472

RESUMO

Small regulatory RNAs (sRNAs) act as key regulators in many bacterial signalling cascades. However, in P. aeruginosa, the sRNAs involved in quorum sensing (QS) regulation and their function are still largely unknown. Here, we explored how the prrH locus sRNA influences P. aeruginosa virulence in the context of the QS regulatory network. First, gain- and loss-of-function studies showed that PrrH affects pyocyanin, elastase and rhamnolipid production; biofilm formation; and swimming and swarming motility and impaired the viability of P. aeruginosa in human whole blood. Next, our investigation disclosed that LasI and PhzC/D were directly repressed by PrrH. In addition, RhlI, the key member of the rhl QS system, diminished the expression of PrrH and enhanced the expression of downstream genes. Bioinformatics analysis found two binding sites of RhlR, the transcription factor of the rhl system, on the promoter region of prrH. Further ß-galactosidase reporter and qPCR assays confirmed that PrrH was transcriptionally repressed by RhlR. Collectively, our data identified a novel RhlI/R-PrrH-LasI/PhzC/PhzD regulatory circuitry that may contribute to P. aeruginosa pathogenesis. Our findings indicate that PrrH is a quorum regulatory RNA (Qrr) in P. aeruginosa and provide new insight into PrrH's function.

12.
JMIR Mhealth Uhealth ; 7(10): e13691, 2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31588909

RESUMO

BACKGROUND: The rates of cannabis use continue to increase among adolescents and the current interventions have modest effects and high rates of relapse following treatment. There is increasing evidence for the efficacy of mobile technology-based interventions for adults with substance use disorders, but there is limited study of this technology in adolescents who use cannabis. OBJECTIVE: The goal of our study was to elucidate elements of an app-based adjunctive intervention for cannabis cessation that resonate with adolescents who use cannabis. METHODS: Adolescents, aged between 14 and 17 years, who used cannabis were recruited from San Diego County high schools. Semistructured focus groups (6 total; N=37) were conducted to examine the ways in which participants used smartphones, including the use of any health behavior change apps, as well as to elicit opinions about elements that would promote engagement with an app-based intervention for adolescent cannabis cessation. An iterative coding structure was used with first cycle structural coding, followed by pattern coding. RESULTS: Themes that emerged from the analysis included (1) youth valued rewards to incentivize the progressive reduction of cannabis use, which included both nontangible rewards that mimic those obtained on social media platforms and prosocial activity-related rewards, (2) having the ability to self-monitor progression, (3) peer social support, (4) privacy and confidentiality discrete logo and name and usernames within the app, and (5) individualizing frequency and content of notifications and reminders. CONCLUSIONS: Integrating content, language, interfaces, delivery systems, and rewards with which adolescents who use cannabis are familiar, engage with on a day-to-day basis, and identify as relevant, may increase treatment engagement and retention for adolescents in substance use treatment. We may increase treatment effectiveness by adapting and individualizing current evidence-based interventions, so that they target the needs of adolescents and are more easily incorporated into their everyday routines.

13.
Orthop Surg ; 11(5): 835-844, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31663282

RESUMO

OBJECTIVES: To evaluate the dynamic changes of key morphology indicators of the lower extremities in the coronal plane with progressing medial compartment knee osteoarthritis (KOA) with an emphasis on gender-dependent regional differences. METHODS: The radiographs of patients with non-traumatic knee pain and varying degrees of genu varus were reviewed. Radiographs were studied in 1538 lower limbs of 883 consecutive patients who visited our hospital from January to July 2017; all patients had long-standing anteroposterior image-splicing radiographs taken of their lower limbs. Morphological indicators of bones and joints that can change the alignment of lower limbs or reflect cartilage wear and soft-tissue relaxation were selected and measured with the help of picture archiving and communication systems. After comparing the data of different genders, the data of males and females was separated into three age groups, <40 years, 40-60 years, >60 years respectively, and then compared among age groups using the Kruskal-Wallis and Mann-Whitney U tests. Scatterplots of age and all the measurements were drawn to determine the strength of the relations. The Pearson correlation test was performed to reveal correlations of measurements and age. RESULTS: Femoral bowing angle (FBA) and joint line convergence angle (JLCA) have obvious differences between different genders (P = 0.001, 0.000, respectively). This suggests that females have greater femoral curvature and joint space angle than males. Significant differences were found in hip-knee-ankle angle (HKA), FBA, distal femoral valgus resection angle (DFVRA), medial proximal tibial angle (MPTA), JLCA, and minimum joint space width (min-JSW) by age groups in females (P = 0.000, 0.000, 0.000, 0.000, 0.003, 0.002, respectively). The difference of mechanical medial distal femoral angle (mMDFA) was significant with P values less than 0.05 deemed significant (P = 0.030). Significant correlations were found between age and all measurements (r = -0.166, 0.253, 0.270, -0.147, 0.089, -0.105, -0.076, respectively, P < 0.01). Whereas, the difference in min-JSW by age group was the only significant one in males (P = 0.001), and no significant correlation was found between age and measurements (r = -0.107, 0.041, 0.134, -0.067, 0.079, -0.134, -0.098, respectively, P > 0.01). CONCLUSIONS: As KOA progressed, both dynamic deformation of lower extremities and degeneration of articular cartilage could be found in females, while no obvious dynamic deformations were found in males. Dynamic deformation of lower extremities was the important feature and the major causative factor of KOA in females.

14.
Cell Death Dis ; 10(10): 774, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31601780

RESUMO

Neonatal jaundice is prevalent among newborns and can lead to severe neurological deficits, particularly sensorimotor dysfunction. Previous studies have shown that bilirubin (BIL) enhances the intrinsic excitability of central neurons and this can potentially contribute to their overexcitation, Ca2+ overload, and neurotoxicity. However, the cellular mechanisms underlying elevated neuronal excitability remain unknown. By performing patch-clamp recordings from neonatal neurons in the rat medial vestibular nucleus (MVN), a crucial relay station for locomotor and balance control, we found that BIL (3 µM) drastically increases the spontaneous firing rates by upregulating the current-mediated voltage-gated sodium channels (VGSCs), while shifting their voltage-dependent activation toward more hyperpolarized potentials. Immunofluorescence labeling and western immunoblotting with an anti-NaV1.1 antibody, revealed that BIL elevates the expression of VGSCs by promoting their recruitment to the membrane. Furthermore, we found that this VGSC-trafficking process is Ca2+ dependent because preloading MVN neurons with the Ca2+ buffer BAPTA-AM, or exocytosis inhibitor TAT-NSF700, prevents the effects of BIL, indicating the upregulated activity and density of functional VGSCs as the core mechanism accountable for the BIL-induced overexcitation of neonatal neurons. Most importantly, rectification of such overexcitation with a low dose of VGSC blocker lidocaine significantly attenuates BIL-induced cell death. We suggest that this enhancement of VGSC currents directly contributes to the vulnerability of neonatal brain to hyperbilirubinemia, implicating the activity and trafficking of NaV1.1 channels as a potential target for neuroprotection in cases of severe jaundice.

15.
Microbiologyopen ; : e943, 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31602821

RESUMO

Chitin is one of the key components of fungal cell wall, and chitin deacetylases (CDAs) have been found in fungi; however, their functions remain unknown. Aspergillus fumigatus is known to cause fatal invasive aspergillosis (IA) among immunocompromised patients with a high mortality rate. Although the A. fumigatus cell wall has long been taken as a unique target for drug development, its dynamic remodeling is complicated and not well understood. Seven putative CDAs are annotated in the A. fumigatus genome. In this study, we analyzed the function of the putative CDAs, Cod4 and Cod7, in A. fumigatus. Biochemical analysis of recombinant proteins showed that Cod4 preferentially deacetylated (GlcNAc)4 and was less active on chitooligosaccharides with DP > 5, whereas Cod7 was unable to catalyze deacetylation. Simulation of three-dimensional structure revealed that both Cod4 and Cod7 shared a similar folding pattern with HyPgdA from Helicobacter pylori and, similar to HyPgdA, a substitution of Thr8 by Ala8 in Cod7 abolished its CDA activity. Deletion of the cod4, cod7, or both in A. fumigatus led to polarity abnormality and increased conidiation. Furthermore, the expression level of the genes related to polarity was upregulated in the mutants. Our results demonstrated that Cod4 and Cod7 were involved in polarity, though Cod4 was inactive.

16.
JCI Insight ; 4(19)2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31578313

RESUMO

Cetuximab, an EGFR-blocking antibody, is currently approved for treatment of metastatic head and neck squamous cell carcinoma (HNSCC), but its response rate is limited. In addition to blocking EGFR-stimulated cell signaling, cetuximab can induce endocytosis of ASCT2, a glutamine transporter associated with EGFR in a complex, leading to glutathione biosynthesis inhibition and cellular sensitization to ROS. Pyruvate dehydrogenase kinase-1 (PDK1), a key mitochondrial enzyme overexpressed in cancer cells, redirects glucose metabolism from oxidative phosphorylation toward aerobic glycolysis. In this study, we tested the hypothesis that targeting PDK1 is a rational approach to synergize with cetuximab through ROS overproduction. We found that combination of PDK1 knockdown or inhibition by dichloroacetic acid (DCA) with ASCT2 knockdown or with cetuximab treatment induced ROS overproduction and apoptosis in HNSCC cells, and this effect was independent of effective inhibition of EGFR downstream pathways but could be lessened by N-acetyl cysteine, an anti-oxidative agent. In several cetuximab-resistant HNSCC xenograft models, DCA plus cetuximab induced marked tumor regression, whereas either agent alone failed to induce tumor regression. Our findings call for potentially novel clinical trials of combining cetuximab and DCA in patients with cetuximab-sensitive EGFR-overexpressing tumors and patients with cetuximab-resistant EGFR-overexpressing tumors.

17.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 44(8): 871-877, 2019 Aug 28.
Artigo em Chinês | MEDLINE | ID: mdl-31570673

RESUMO

OBJECTIVE: To observe the changes in serum interleukin-22 (IL-22) level and its correlation with other clinical indexes in patients with essential hypertension and hypertensive renal damage, and to investigate its effects and clinical significance.
 Methods: A total of 97 essential hypertension (EH) patients and 40 healthy control were enrolled in this study. The EH patients were divided into a simple hypertension (SH) group (n=45) and a hypertensive renal damage (HRD) group (n=52) according to 24 h urinary protein (24 h-UPRO) level. Basic clinical data were collected; serum IL-22 level was detected by enzyme-linked immunosorbent assay (ELISA); the proportion of Th22 cells in peripheral blood was evaluated by flow cytometry (FCM); and serum high sensitivity C-reactive protein (hs-CRP) concentration was measured by immune turbidimetry. Correlation analysis was applied between serum IL-22 level and other indexes.
 Results: Serum IL-22 level and Th22 cell proportion in patients with hypertension were significantly higher than those in the healthy controls (all P<0.01). Compared with the SH group, serum IL-22 level and Th22 cell proportion were significantly elevated in the HRD group (P<0.01, P<0.05, respectively). Bivariate linear correlation analysis revealed that serum IL-22 level was positively correlated with systolic blood pressure (SBP), diastolic blood pressure (DBP), and hsCRP (r=0.367, P<0.01; r=0.402, P<0.01; r=0.329, P<0.05); there was also a positive correlation between serum IL-22 concentration and Th22 cell proportion (r=0.478, P<0.01) in the SH group. Serum IL-22 level was positively correlated with 24 h-UPRO level (r=0.318, P<0.05) in the HRD group.
 Conclusion: Serum IL-22 level and peripheral blood Th22 cells are significantly increased in the HRD group compared with the SH group. Serum IL-22 level is closely correlated with extent of hypertensive renal damage, indicating that serum IL-22 level may involve in the pathogenesis of hypertensive renal damage.


Assuntos
Hipertensão , Pressão Sanguínea , Proteína C-Reativa , Humanos , Interleucinas
18.
Stress ; : 1-11, 2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-31591949

RESUMO

Growing evidences have shown that patients recovering from stroke experience high and unremitting stress. Chronic restraint stress (CRS) has been found to exacerbate neurological impairments in an experimental focal cortical ischemia model. However, there have been no studies reporting the effect and mechanism of CRS on intracerebral hemorrhage (ICH). This study aimed to evaluate the effect of CRS on a mouse ICH model. Adult male C57BL mice were subjected to infusion of collagenase IV (to induce ICH) or saline (for sham) into the left striatum. After ICH, animals were stressed with application of CRS protocol for 21 days. Our results showed that CRS significantly exacerbated neurological deficits (Garcia test, corner turn test, and wire grip test) and the ipsilateral brain atrophy and reduced body weight gain after ICH. Immunofluorescence staining indicated that CRS exerted significant suppressive effects on neuron, astrocyte, vascular endothelial cell and pericyte and excessively activated microglia post ICH. All of the key cellular components mentioned above are involved in the neurovascular unit (NVU) remodeling in the peri-hemorrhagic region after ICH. Western blot results showed that matrix metalloproteinase (MMP)-9 and tight junction (TJ) proteins including zonula occludens-1, occludin and claudin-5 were increased after ICH, but MMP-9 protein was further up-regulated and TJ-related proteins were down-regulated by CRS. In addition, ICH-induced activation of endoplasmic reticulum stress and apoptosis were further strengthened by CRS. Collectively, CRS exacerbates neurological deficits and disrupts the remodeling of the peri-hemorrhagic NVU after ICH, which may be associated with TJ proteins degradation and excessive activation of MMP-9 and endoplasmic reticulum stress-apoptosis. LAY SUMMARY CRS exacerbates neurological deficits and disrupts the remodeling of the NVU in the recovery stage after ICH, which suggest that monitoring chronic stress levels in patients recovering from ICH may merit consideration in the future.

19.
ACS Appl Mater Interfaces ; 11(38): 35030-35038, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31487146

RESUMO

Garnet-type solid-state electrolytes (SSEs) show a promising application in solid-state Li batteries. Poor interfacial contact with lithium causing large interfacial impedance and dendrite penetration is a problem. Inspired by unique H+/Li+ exchange of garnet electrolyte, we used an AgNO3 aqueous solution induced strategy to construct a lithiophilic layer in situ on the garnet surface without any specific apparatus. Experimental analysis reveals the uniform distribution of Ag nanoparticles and significantly enhanced affinity between the solid state electrolyte (SSE) and Li anode for the Li-Ag alloying. As expected, the interfacial area specific resistance (ASR) is greatly reduced to ∼4.5 Ω cm2, accompanying with long-cycling stability for ∼3500 h at 0.2 mA cm-2 and high critical current density of 0.75 mA cm-2. With modified SSEs, quasi-solid-state batteries with a LiFePO4 or LiNi0.5Co0.2Mn0.3O2 cathode operate well at room temperature and an all-solid-state LiFePO4/garnet/Li battery displays good cycling stability for over 200 cycles at 60 °C.

20.
Brain ; 142(10): 3099-3115, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31504219

RESUMO

The loss-of-function mutation in PARK7/DJ-1 is one of the most common causes of autosomal recessive Parkinson's disease, and patients carrying PARK7 mutations often exhibit both a progressive movement disorder and emotional impairment, such as anxiety. However, the causes of the emotional symptom accompanying PARK7-associated and other forms of Parkinson's disease remain largely unexplored. Using two-photon microscopic Ca2+ imaging in awake PARK7-/- and PARK7+/+ mice, we found that (i) PARK7-/- neurons in the frontal association cortex showed substantially higher circuit activity recorded as spontaneous somatic Ca2+ signals; (ii) both basal and evoked dopamine release remained intact, as determined by both electrochemical dopamine recordings and high performance liquid chromatography in vivo; (iii) D2 receptor expression was significantly decreased in postsynaptic frontal association cortical neurons, and the hyper-neuronal activity were rescued by D2 receptor intervention using either local pharmacology or viral D2 receptor over-expression; and (iv) PARK7-/- mice showed anxiety-like behaviours that were rescued by either local D2 receptor pharmacology or overexpression. Thus, for first time, we demonstrated a robust D2 receptor-dependent phenotype of individual neurons within the prefrontal cortex circuit in awake parkinsonian mice that linked with anxiety. Our work sheds light on early-onset phenotypes and the mechanisms underlying Parkinson's disease by imaging brain circuits in an awake mouse model.

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