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1.
Bioresour Technol ; 293: 122023, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31472407

RESUMO

The differences of crude oil recovery ratio resulted in different levels of crude oil in actual hydrolyzed polyacrylamide (HPAM)-containing wastewater. The effect of crude oil on HPAM biotransformation was explored from bioresource production, enzymatic activity and microbial function. In aerobic biosystems, the highest polyhydroxyalkanoate (PHA) yield (19.6%-40.2%) and dehydrogenase (DH) activity (4.06-8.32 mg·g-1 VSS) occurred in the 48th hour, and increased with crude oil concentration (0-400 mg·L-1). In anoxic biosystems, the highest PHA yield (24.5%-50.5%) and DH activity (3.24-6.69 mg·g-1 VSS) occurred in the 72nd hour, and increased with crude oil concentration. The higher substrate removal (38.5%-65.7%) occurred in aerobic biosystems, while the higher PHA accumulation occurred in anoxic biosystems. PHA yield, DH activity and HPAM removal were related. Microbial function related to HPAM biodegradation and PHA synthesis was discussed. The main function of Pseudomonas and Bacillus in aerobic biosystems was to degrade HPAM, and in anoxic biosystems was to synthesize PHA.

2.
Neuroscience ; 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31487541

RESUMO

JLX001, a novel compound with similar structure with cyclovirobuxine D (CVB-D), has been proved to exert therapeutical effects on permanent focal cerebral ischemia. However, the protective effects of JLX001 on cerebral ischemia/reperfusion (I/R) injury and its anti-apoptotic effects have not been reported. We investigated the efficacy of JLX001 in two pharmacodynamic tests (pre-treatment test and post-treatment) with rats subjected to middle cerebral artery occlusion/reperfusion (MCAO/R). The pharmacodynamic tests demonstrated that JLX001 ameliorated I/R injury by reducing infarct sizes and brain edema. The results of Morris water maze, neurological scores, cylinder test and posture reflex test implied that JLX001 improved the learning, memory and motor ability after MCAO/R in the long term. Anti-apoptotic effects of JLX001 and its regulation of cytosolic c-Jun N-terminal Kinases (JNKs) signal pathway were confirmed in vivo by co-immunofluorescence staining and western immunoblotting. Furthermore, primary cortical neuron cultures were prepared and exposed to oxygen glucose deprivation/reoxygenation (OGD/R) for in vitro studies. Cytotoxicity test and mitochondrial membrane potential (MMP) test showed that JLX001 enhanced cell survival rate and maintained MMP. Flow cytometry and TdT-mediated dUTP-X nick end labeling (TUNEL) staining demonstrated the anti-apoptotic effects of JLX001 in vitro. Likewise, JLX001 regulated JNK signal pathway in vivo, which was also confirmed by western immunoblotting. Collectively, this study presents the first evidence that JLX001 exerted protective effects against I/R injury by reducing neuronal apoptosis via down-regulating JNK signaling pathway.

3.
Cereb Cortex ; 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31504260

RESUMO

The compromised abilities to understand speech and localize sounds are two hallmark deficits in aged individuals. Earlier studies have shown that age-related deficits in cortical neural timing, which is clearly associated with speech perception, can be partially reversed with auditory training. However, whether training can reverse aged-related cortical changes in the domain of spatial processing has never been studied. In this study, we examined cortical spatial processing in ~21-month-old rats that were trained on a sound-azimuth discrimination task. We found that animals that experienced 1 month of training displayed sharper cortical sound-azimuth tuning when compared to the age-matched untrained controls. This training-induced remodeling in spatial tuning was paralleled by increases of cortical parvalbumin-labeled inhibitory interneurons. However, no measurable changes in cortical spatial processing were recorded in age-matched animals that were passively exposed to training sounds with no task demands. These results that demonstrate the effects of training on cortical spatial domain processing in the rodent model further support the notion that age-related changes in central neural process are, due to their plastic nature, reversible. Moreover, the results offer the encouraging possibility that behavioral training might be used to attenuate declines in auditory perception, which are commonly observed in older individuals.

4.
Liver Int ; 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31505104

RESUMO

BACKGROUND AND AIMS: The prognostic accuracy of individual hepatocellular carcinoma (HCC) patient in each Barcelona Clinic Liver Cancer (BCLC) stage is unclear. We aimed to develop and validate an albumin-bilirubin (ALBI) grade-based nomogram of BCLC to estimate survival for individual HCC patient. METHODS: Between 2002 and 2016, 3690 patients with newly diagnosed HCC were prospectively enrolled and retrospectively analyzed. Patients were randomly split into derivation and validation cohort by 1:1 ratio. Multivariate Cox proportional hazards model was used to generate the nomogram from tumor burden, ALBI grade and performance status (PS). The concordance index and calibration plot were determined to evaluate the performance of this nomogram. RESULTS: Beta coefficients from the Cox model were used to assign nomogram points to different degrees of tumor burden, ALBI grade and PS. The scores of the nomogram ranged from 0 to 24, and were used to predict 3- and 5-year patient survival. The concordance index of this nomogram was 0.77 (95% confidence interval [CI]: 0.71-0.81) in the derivation cohort and 0.76 (95% CI: 0.71-0.81) in the validation cohort. The calibration plots to predict both 3- and 5-year survival rate well matched the 45-degree ideal line for both cohorts, except for ALBI-based BCLC stage 0 in the validation cohort. CONCLUSIONS: The proposed ALBI-based nomogram of BCLC system is a simple and feasible strategy in the precision medicine era. Our data indicate it is a straightforward and user-friendly prognostic tool to estimate the survival of individual HCC patient except for very early stage patients.

5.
Int J Mol Sci ; 20(16)2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31443312

RESUMO

Hepatocellular carcinoma (HCC) is a primary malignancy of the liver. In basic studies, the regulation of autophagy has offered promising results for HCC treatment. This study aimed to address the question of whether amiodarone can improve survival rates in HCC patients associated with autophagy. Using datasets from the National Health Insurance Research Database, we enrolled patients over 18 years of age that had been diagnosed with HCC between January 1997 and December 2010. Amiodarone and non-amiodarone users were matched at a 1:1 frequency, according to all variables. Additionally, HepG2 cells treated with amiodarone were evaluated by cell viability and autophagic change. Autophagic signaling was examined by immunoblotting and tissue array immunohistochemistry. Of the 10,946 patients diagnosed with HCC, each cohort included 221 patients after 1:1 propensity score matching. The median survival was 36.70 months for the amiodarone users, and 24.48 months for the non-amiodarone users. After adjusting for age, gender, comorbidities and treatment, amiodarone users had a significantly lower risk of mortality. Amiodarone users also demonstrated an improved 3-year survival rate. Furthermore, amiodarone treatment-induced autophagy in HepG2 cells was demonstrated by autophagosome formation associated with increasing LC3B-II, P62, and Beclin-1 expression. Autophagic flux also increased following amiodarone treatment with bafilomycin A1. SiRNA of LC3B knocked down endogenous LC3B formation and restored HepG2 cell viability. This study provides epidemiologic evidence that amiodarone via autophagic degradation machinery may offer survival benefits for HCC patients with a history of arrhythmia. Further randomized, blinded, and placebo-controlled trials are warranted for patients with HCC.

6.
Pathol Res Pract ; : 152555, 2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31445715

RESUMO

Recent evidence highlights that microRNAs serve as crucial regulators of tumorigenesis, including non-small cell lung cancer (NSCLC). The present study was designed to investigate the expression profile, clinical significance and biological role of miR-421 in NSCLC. The results showed that miR-421 expression was markedly increased in NSCLC tissues and cell lines. Further experimental data indicated that knockdown of miR-421 significantly inhibited NSCLC cell proliferation and induced cell cycle arrest in vitro. The migratory and invasive abilities of NSCLC cells were also attenuated following miR-421 knockdown. Furthermore, PDCD4 was identified as a direct target of miR-421, and its expression was inversely correlated with miR-421 expression in NSCLC tissues. PDCD4 also abrogated the oncogenic role of miR-421 in NSCLC cells. Collectively, our study revealed that miR-421 is significantly upregulated in NSCLC and might represent a potential therapeutic target for NSCLC patients.

7.
Transplant Proc ; 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31447189

RESUMO

BACKGROUND: There is little evidence about whether mammalian target of rapamycin (mTOR) inhibitor could prevent post-kidney transplant (KT) urothelial carcinoma (UC) or not. The aim of this study is to analyze the role of mTOR inhibitor add-on in tacrolimus-based kidney transplant recipients. METHOD: The data were obtained from the Kaohsiung Chang Gung Memorial Hospital using the Chang Gung Research Database and retrospectively reviewed from January 2000 to December 2015. Patients then were categorized into 2 groups: group FK (more than 2-year tacrolimus [FK] prescription) and group FK + mTOR inhibitor (more than 2-year tacrolimus plus at least 6-month continued sirolimus prescription). The primary end point is post-KT UC development. The secondary end point is mTOR inhibitor add-on effect on renal function deterioration episode. RESULTS: There were 140 patients with tacrolimus-based immunosuppressant (group FK) and 82 patients with tacrolimus-based and add-on mTOR inhibitor regimen (group FK + mTOR inhibitor). The follow-up duration, sex distribution, and combined mycophenolate mofetil rate are similar in both groups. Younger age, lower tacrolimus trough level, lower UC incidence, and longer KT-to-UC interval were observed. Short- to intermediate-term results revealed noninferior graft outcome by creatinine level or creatinine deterioration. CONCLUSIONS: In our preliminary result, mTOR inhibitor add-on in patients with tacrolimus-based regimen revealed less post-KT UC occurrence. In addition, noninferior graft outcome was also observed. In Taiwan, a high UC prevalence area, mTOR inhibitor add-on strategy can be considered as a preventive strategy for UC after KT.

8.
Acad Radiol ; 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31447259

RESUMO

RATIONALE AND OBJECTIVES: Clinically-relevant quantitative measures of task-based image quality play key roles in effective optimization of medical imaging systems. Conventional phantom-based measures do not adequately reflect the real-world image quality of clinical Computed Tomography (CT) series which is most relevant for diagnostic decision-making. The assessment of detectability index which incorporates measurements of essential image quality metrics on patient CT images can overcome this limitation. Our current investigation extends and validates the technique on standard-of-care clinical cases. MATERIALS AND METHODS: We obtained a clinical CT image dataset from an Institutional Review Board-approved prospective study on colorectal adenocarcinoma patients for detecting hepatic metastasis. For this study, both perceptual image quality and lesion detection performance of same-patient CT image series with standard and low dose acquisitions in the same breath hold and four processing algorithms applied to each acquisition were assessed and ranked by expert radiologists. The clinical CT image dataset was processed using the previously validated method to estimate a detectability index for each known lesion size in the size distribution of hepatic lesions relevant for the imaging task and for each slice of a CT series. We then combined these lesion-size-specific and slice-specific detectability indexes with the size distribution of hepatic lesions relevant for the imaging task to compute an effective detectability index for a clinical CT imaging condition of a patient. The assessed effective detectability indexes were used to rank task-based image quality of different imaging conditions on the same patient for all patients. We compared the assessments to those by expert radiologists in the prospective study in terms of rank order agreement between the rankings of algorithmic and visual assessment of lesion detection and perceptual quality. RESULTS: Our investigation indicated that algorithmic assessment of lesion detection and perceptual quality can predict observer assessment for detecting hepatic metastasis. The algorithmic and visual assessment of lesion detection and perceptual quality are strongly correlated using both the Kendall's Tau and Spearman's Rho methods (perfect agreement has value 1): for assessment of lesion detection, 95% of the patients have rank correlation coefficients values exceeding 0.87 and 0.94, respectively, and for assessment of perceptual quality, 0.85 and 0.94, respectively. CONCLUSION: This study used algorithmic detectability index to assess task-based image equality for detecting hepatic lesions and validated it against observer rankings on standard-of-care clinical CT cases. Our study indicates that detectability index provides a robust reflection of overall image quality for detecting hepatic lesions under clinical CT imaging conditions. This demonstrates the concept of utilizing the measure to quantitatively assess the quality of the information content that different imaging conditions can provide for the same clinical imaging task, which enables targeted optimization of clinical CT systems to minimize clinical and patient risks.

9.
J Biomed Sci ; 26(1): 59, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31434568

RESUMO

Increasing evidences have shown strong associations between gut microbiota and many human diseases, and understanding the dynamic crosstalks of host-microbe interaction in the gut has become necessary for the detection, prevention, or therapy of diseases. Many reports have showed that diet, nutrient, pharmacologic factors and many other stimuli play dominant roles in the modulation of gut microbial compositions. However, it is inappropriate to neglect the impact of host factors on shaping the gut microbiota. In this review, we highlighted the current findings of the host factors that could modulate the gut microbiota. Particularly the epithelium-associated factors, including the innate immune sensors, anti-microbial peptides, mucus barrier, secretory IgAs, epithelial microvilli, epithelial tight junctions, epithelium metabolism, oxygen barrier, and even the microRNAs are discussed in the context of the microbiota shaping. With these shaping factors, the gut epithelial cells could select the residing microbes and affect the microbial composition. This knowledge not only could provide the opportunities to better control many diseases, but may also be used for predicting the success of fecal microbiota transplantation clinically.

10.
Sci Rep ; 9(1): 12022, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31427600

RESUMO

As the natural boundary between the Yunnan-Guizhou Plateau and the Hengduan Mountains in China, the large-scale prominent terrain of Ailaoshan Mountain leads to obvious regional differences in climate and vegetation. In this article, a comparative analysis is made on both species composition and floristic components of spore pollen (SP) in two sample soil plots near the main peak of Ailaoshan Mountain. The results show that there is a remarkable difference between the western and eastern sample plots. The climate or meteorology characteristics are likely the main reasons accounting for the differences in habitat characteristics and plant sample investigation results. The tropical genera elements of sediment SPs are higher in the western sample plot (6.8%) than in the eastern sample plot (4.7%) because the western plot is controlled by the Indian summer monsoon at all times. The north temperate elements of sediment SP are lower in the western plot (13.4%) than in the eastern plot (26.4%) because the eastern plot is evidently sometimes influenced by the East Asian winter monsoon. In general, Ailaoshan Mountain may be one of important physical geographical boundaries between the interacting regions influenced by both the Indian summer monsoon and the East Asian winter monsoon.

11.
Environ Pollut ; 254(Pt A): 113016, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31400666

RESUMO

Dissolved organic carbon (DOC) has a major influence upon sorption/desorption and transport of hydrophobic organic contaminants (HOCs) in soil environments. However, the molecular mechanisms of DOC sorption and its effects on aged HOC desorption in contaminated soils still remain largely unclear. Here, effects of three different DOC (one from commercial peat and two from biochars produced at 300 °C and 500 °C pyrolysis temperatures, respectively) and oxalate (as a reference) on abiotic desorption behavior of aged phenanthrene from three agricultural soils were investigated. Results showed that desorption of aged phenanthrene from soils was predominantly dependent on soil organic carbon content. The presence of DOC and oxalate resulted in higher desorption of phenanthrene compared to water alone, and the effects were positively related to soil organic carbon content and DOC/oxalate concentration. The facilitating effects of DOC were further increased during the second consecutive desorption, whereas oxalate had no such effect. Ultra-high-resolution Fourier transform-ion cyclotron resonance-mass spectrometry confirmed the molecular fractionation of DOC at the soil-water interface during DOC sorption. Specifically, the DOC molecules with O-rich moieties were preferentially adsorbed, whereas the molecules with phenolic and aromatic structures were selectively retained in the soil solutions through competitive displacement and co-sorption reactions during sorption. The enriched phenyl structures in the retained DOC facilitated its association with phenanthrene in the solutions and thus the release of phenanthrene from the soils. In contrast, oxalate replaced some organic carbon from the soils and thus released the associated phenanthrene into the solutions. Our findings highlight the importance of the molecular composition and structure of DOC for the desorption of phenanthrene in soil-water environments, which may help improve our understanding of the release and transport of organic compounds in the environments.

12.
Int J Mol Sci ; 20(17)2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31454988

RESUMO

Diverse transcriptional controls in the dorsal horn have been observed in pain hypersensitivity. However, the understanding of the exact causes and mechanisms of neuropathic pain development is still fragmentary. Here, the results demonstrated nerve injury decreased the expression of spinal hairy and enhancer of split 1 (Hes1), a transcriptional repressor, and enhanced metabotropic glutamate receptor subtype 5 (mGluR5) transcription/expression, which was accompanied with behavioral allodynia. Moreover, nerve injury decreased Hes1 levels and reciprocally increased cyclin dependent kinase-9 (CDK9) levels and recruited CDK9 to phosphorylate RNA polymerase II (RNAPII) in the promoter fragments of mGluR5, thereby enhancing mGluR5 transcription/expression in the dorsal horn. These effects were also induced by intrathecally administering naïve rats with Hes1 small interfering RNA (siRNA). Conversely, Hes1 overexpression using intrathecal lentiviral vectors in nerve injury rats produced reversal of pain behavior and reversed protein expressions, phosphorylation, and coupling to the promoter segments in the dorsal horn. Collectively, the results in this study indicated nerve injury diminishes spinal Hes1-dependent suppression of CDK9-dependent RNAPII phosphorylation on the mGluR5 promoter that possibly enhances mGluR5 transcription/expression for neuropathic pain development.

14.
BMC Cancer ; 19(1): 842, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31455250

RESUMO

BACKGROUND: Helicobacter pylori (H. pylori) is thought to have an oncogenic effect on the development of gastric malignancies. However, the effect of H. pylori status on the prognosis of gastric diffuse large B-cell lymphoma (DLBCL) remains unconfirmed. This study aimed to identify the prognostic importance of H. pylori infection in de novo gastric DLBCL. METHODS: One hundred and twenty-nine patients diagnosed with primary de novo gastric DLBCL at the West China Hospital of Sichuan University from 1st January 2009 to 31st May 2016 were included. The clinical features of the patients were documented. H. pylori status was assessed via urease breath tests and histologic examinations. The prognostic value of H. pylori was verified via univariate and multivariate analyses. RESULTS: Over a median follow-up of 52.2 months (range 4-116), the 5-year overall survival (OS) for all patients was 78.7%. Patients with H. pylori infections had significantly better 5-year PFS and OS than did the H. pylori-negative subgroup (5-year PFS, 89.3% vs. 74.1%, P = 0.040; 5-year OS, 89.7% vs. 71.8%, P = 0.033). Negative H. pylori status and poor ECOG performance were independent negative prognostic indicators for both PFS and OS (PFS, P = 0.045 and P = 0.001, respectively; OS, P = 0.021 and P < 0.001, respectively). CONCLUSIONS: H. pylori status in de novo gastric DLBCL can be a promising predictor of disease outcome, and patients with negative H. pylori status require careful follow-up since they tend to have a worse outlook.

15.
Med Phys ; 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31465538

RESUMO

PURPOSE: Automated assessment of perceptual image quality on clinical Computed Tomography (CT) data by computer algorithms has the potential to greatly facilitate data-driven monitoring and optimization of CT image acquisition protocols. The application of these techniques in clinical operation requires the knowledge of how the output of the computer algorithms corresponds to clinical expectations. This study addressed the need to validate algorithmic image quality measurements on clinical CT images with preferences of radiologists and determine the clinically acceptable range of algorithmic measurements for abdominal CT examinations. MATERIALS AND METHODS: Algorithmic measurements of image quality metrics (organ HU, noise magnitude, and clarity) were performed on a clinical CT image dataset with supplemental measures of noise power spectrum from phantom images using techniques developed previously. The algorithmic measurements were compared to clinical expectations of image quality in an observer study with seven radiologists. Sets of CT liver images were selected from the dataset where images in the same set varied in terms of one metric at a time. These sets of images were shown via a web interface to one observer at a time. First, the observer rank ordered the CT images in a set according to his/her preference for the varying metric. The observer then selected his/her preferred acceptable range of the metric within the ranked images. The agreement between algorithmic and observer rankings of image quality were investigated and the clinically acceptable image quality in terms of algorithmic measurements were determined. RESULTS: The overall rank order agreements between algorithmic and observer assessments were 0.90, 0.98, and 1.00 for noise magnitude, liver parenchyma HU, and clarity, respectively. The results indicate a strong agreement between the algorithmic and observer assessments of image quality. Clinically acceptable thresholds (median) of algorithmic metric values were (17.8, 32.6) HU for noise magnitude, (92.1, 131.9) for liver parenchyma HU, and (0.47, 0.52) for clarity. CONCLUSIONS: The observer study results indicated that these algorithms can robustly assess the perceptual quality of clinical CT images in an automated fashion. Clinically acceptable ranges of algorithmic measurements were determined. The correspondence of these image quality assessment algorithms to clinical expectations paves the way towards establishing diagnostic reference levels in terms of clinically acceptable perceptual image quality and data-driven optimization of CT image acquisition protocols.

16.
Small ; : e1902123, 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31468655

RESUMO

The global tobacco epidemic is still a devastating threat to public health. Toxic reactive oxygen species (ROS) in the cigarette smoke cannot be efficiently eliminated by currently available cigarette filters. The resultant oxidative stress causes severe lung injury and further diseases. To tackle this challenge, herein, a novel copper tannic acid coordination (CuTA) nanozyme is reported as a highly active and thermostable ROS scavenger. The CuTA nanozyme exhibits intrinsic superoxide dismutase-like activity, catalase-like activity, and hydroxyl radical elimination capacity. These synergistic antioxidant abilities make the CuTA nanozyme a promising candidate for the improvement of commercial cigarette filters. Mouse model results show that commercial cigarettes loaded with CuTA nanozyme efficiently scavenge ROS in the cigarette smoke, reduce oxidative stress-induced lung inflammation, and minimize the resultant acute lung injury. The developed CuTA nanozyme offers an efficient ROS scavenger with multiple antioxidant ability and opens up new opportunities for the modification of cigarette filters to reduce the toxic effects of cigarette smoke.

17.
Drug Metab Dispos ; 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31387871

RESUMO

The identification of non-opioid alternatives to treat chronic pain has received a great deal of interest in recent years. Recently, the engineering of a series of Nav1.7 inhibitory peptide-antibody conjugates has been reported and herein, the preclinical efforts to identify novel approaches to characterize the pharmacokinetic properties of the peptide conjugates are described. A cryopreserved plated mouse hepatocyte assay was designed to measure the depletion of the peptide-antibody conjugates from the media, with a correlation being observed between percent remaining in the media and in vivo clearance (Pearson r = -0.5525). Physicochemical (charge and hydrophobicity), receptor-binding (FcRn) and in vivo pharmacokinetic data were generated and compared to the results from an in vitro our hepatocyte assay that was hypothesized to encompass all of the aforementioned properties. Correlations were observed between hydrophobicity, FcRn binding, depletion rates from the hepatocyte assay and ultimately, in vivo clearance. Subsequent studies identified potential roles for the low-density lipoprotein and mannose/galactose receptors in the association of the Nav1.7 peptide conjugates with mouse hepatocytes, though in vivo studies suggested that FcRn was still the primary receptor involved in determining the pharmacokinetics of the peptide conjugates. Ultimately, the use of the cryopreserved hepatocyte assay along with FcRn binding and hydrophobic interaction chromatography provided an efficient and integrated approach to rapidly triage molecules for advancement while reducing the number of in vivo pharmacokinetic studies. SIGNIFICANCE STATEMENT: While multiple in vitro and in silico tools are available in small molecule drug discovery, pharmacokinetic characterization of protein therapeutics is still highly dependent upon the use of in vivo studies in preclinical species. The current work demonstrates the combined use of cryopreserved mouse hepatocytes, hydrophobic interaction chromatography and FcRn binding to characterize a series of Nav1.7 peptide-antibody conjugates prior to conducting in vivo studies, thus providing a means to rapidly evaluate novel protein therapeutic platforms while concomitantly reducing the number of in vivo studies conducted in preclinical species.

18.
J BUON ; 24(3): 897-904, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31424639

RESUMO

Exosomes, especially the tumor-derived exosomes (TDEs), are extracellular vesicles released by many kinds of cells, which are involved in several biological and pathological processes. Their contents mainly include DNA, RNA and proteins. The message could be transmitted in neighboring or distant cells by secreting extracellular vesicles (EVs). Exosomes are a main intercellular communication regulator because they are involved and interact with intracellular signaling pathways. Exosomes can be detected in the tumor microenvironment, and there is growing evidence that TDEs are active in tumor growth, angiogenesis, invasion and metastasis, as well as immune responses and drug resistance. All of the functions mentioned above make it clear that exosomes have an important role in tumors. This review focuses on the origin and structure of TDEs and their important biological functions in the environment due to cell-to-cell intercellular communication.

19.
Am J Clin Oncol ; 42(9): 698-704, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31335351

RESUMO

OBJECTIVE: The Milan criteria are recommended as the major reference for liver transplantation in patients with small hepatocellular carcinoma (HCC). However, alternative anticancer treatments are often utilized due to severe donor organ shortage. This study aimed to develop and validate an albumin-bilirubin (ALBI) grade-based prognostic model to stratify survival in patients within Milan criteria undergoing nontransplant therapy. PATIENTS AND METHODS: A total of 1655 patients were assigned into the derivation and validation cohort according to treatment modalities. Multivariate analysis was used to identify independent predictors of survival in the derivation cohort. An ALBI-based model was evaluated in the validation cohort. RESULTS: In the Cox multivariate model, age 65 years or older (hazard ratio [HR]=1.576, P<0.001), serum α-fetoprotein (AFP) level >100 ng/mL (HR=1.671, P<0.001), ascites (HR=1.808, P<0.001), performance status 1 to 4 (HR=1.738, P<0.001), ALBI grade 2 (HR=1.827, P<0.001), and ALBI grade 3 (HR=3.589, P<0.001) were independent predictors of poor survival in the derivation cohort. An ALBI-based prognostic model with a total of 0 to 6 points was derived with the sum of 5 variables: 1 point each for age 65 years or older, AFP >100 ng/mL, presence of ascites, performance status 1 to 4, and ALBI grade 2, and 2 points for ALBI grade 3. This model can accurately predict long-term outcome in the validation cohort (P<0.001) and discriminate survival in patients stratified by curative and noncurative treatments (both P<0.001). CONCLUSION: The proposed ALBI grade-based model is feasible in predicting survival in HCC patients within the Milan criteria, and helps identify high-risk patients who need timely liver transplantation.

20.
Int J Mol Sci ; 20(13)2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31266224

RESUMO

Extracts from the Nepenthes plant have anti-microorganism and anti-inflammation effects. However, the anticancer effect of the Nepenthes plant is rarely reported, especially for breast cancer cells. Here, we evaluate the antitumor effects of the ethyl acetate extract of Nepenthes thorellii x (ventricosa x maxima) (EANT) against breast cancer cells. Cell viability and flow cytometric analyses were used to analyze apoptosis, oxidative stress, and DNA damage. EANT exhibits a higher antiproliferation ability to two breast cancer cell lines (MCF7 and SKBR3) as compared to normal breast cells (M10). A mechanistic study demonstrates that EANT induces apoptosis in breast cancer cells with evidence of subG1 accumulation and annexin V increment. EANT also induces glutathione (GSH) depletion, resulting in dramatic accumulations of reactive oxygen species (ROS) and mitochondrial superoxide (MitoSOX), as well as the depletion of mitochondrial membrane potential (MMP). These oxidative stresses attack DNA, respectively leading to DNA double strand breaks and oxidative DNA damage in γH2AX and 8-oxo-2'deoxyguanosine (8-oxodG) assays. Overall these findings clearly revealed that EANT induced changes were suppressed by the ROS inhibitor. In conclusion, our results have shown that the ROS-modulating natural product (EANT) has antiproliferation activity against breast cancer cells through apoptosis, oxidative stress, and DNA damage.

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