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1.
Aging (Albany NY) ; 12(21): 22174-22198, 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33146634

RESUMO

Senescence of smooth muscle cells (SMCs) has a crucial role in the pathogenesis of abdominal aortic aneurysm (AAA), a disease of vascular degeneration. Perturbation of cellular ribosomal DNA (rDNA) transcription triggers nucleolar stress response. Previously we demonstrated that induction of nucleolar stress in SMCs elicited cell cycle arrest via the ataxia-telangiectasia mutated (ATM)/ATM- and Rad3-related (ATR)-p53 axis. However, the specific roles of nucleolar stress in vascular degeneration remain unexplored. In the present study, we demonstrated for the first time that in both human and animal AAA tissues, there were non-coordinated changes in the expression of RNA polymerase I machinery components, including a downregulation of transcription initiation factor-IA (TIF-IA). Genetic deletion of TIF-IA in SMCs in mice (smTIF-IA-/-) caused spontaneous aneurysm-like lesions in the aorta. In vitro, induction of nucleolar stress triggered a non-canonical DNA damage response, leading to p53 phosphorylation and a senescence-like phenotype in SMCs. In human AAA tissues, there was increased nucleolar stress in medial cells, accompanied by localized DNA damage response within the nucleolar compartment. Our data suggest that perturbed rDNA transcription and induction of nucleolar stress contribute to the pathogenesis of AAA. Moreover, smTIF-IA-/- mice may be a novel animal model for studying spontaneous AAA-like vascular degenerations.

2.
Biomater Sci ; 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33112303

RESUMO

Gene therapy is a promising strategy for treating ischemic disease by solving the dual dilemma of ischemia and inflammation. However, its development remains limited by inefficient gene transfection. Hence, we propose a "dual genes + all-adaptive carrier" idea. We have innovatively co-delivered eNOS gene and the ZNF580 gene encoding its transcription factor to enhance the efficiency of eNOS expression. The overexpressed ZNF580 protein significantly promotes angiogenesis via regulating the transcription of multiple genes. This implies a potential synergistic effect of eNOS and ZNF580 genes in anti-ischemic therapy. Additionally, we have designed an all-adaptive gene carrier with cascaded bio-responsive functions based on the characteristic bio-signals of the ischemic site (including extracellular excessive matrix metalloproteinase-2, the endo/lysosomal pH gradient and high cytoplasmic glutathione level). This carrier can sequentially overcome transfection bottlenecks and achieve high transfection. Excitingly, this cascaded bio-responsive delivery strategy remarkably enhanced blood perfusion, accelerated angiogenesis and alleviated inflammation in critical limb ischemia (CLI) mice, which was attributed to the combined effects of pro-angiogenic ZNF580 expression and synergistically produced eNOS expression. Thereby, we believe that the co-delivery of eNOS and ZNF580 genes assisted by a cascaded bio-responsive carrier is a powerful strategy to treat CLI.

3.
J Food Biochem ; : e13362, 2020 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-32662541

RESUMO

Banana (Musa nana Lour.) have the effect of anti-obesity and lipid modulating properties. However, the influences of banana pulp dietary fibers (BP-DF) on metabolic syndrome (MetS) and gut microbiota (GM) are unknown. In this research, we explore a novel strategy for dietary BP-DF on attenuation of lipid metabolic disease, GM disorder, and associated mechanisms in high-fat diet (HFD) mice. BP-DF can strongly suppress on HFD caused body weight and epididymal fat mass gain, and significantly improved serum lipid profiles, liver lipid profiles, and intestinal function. BP-DF also significantly improved fecal short-chain fatty acids formation and fecal ammonia content. BP-DF impacted the intestinal microorganism at all kinds of taxonomic levels by increasing the proportions of beneficial Lactobacillus, Bacteroidales _S24_7_group, and Alloprevotella and decreasing the disease or obesity associated Sutterella, Streptococcaceae, and Erysipelotrichaceae. The experiments show that BP-DF may use as a functional ingredient for preventing obesity, MetS, and intestinal microorganism imbalance. PRACTICAL APPLICATIONS: Obesity result in many metabolic complications, and it poses a great threat to people's health. Nowadays, the introduction of DF may lead to the development of a new strategy in the treatment of obesity and its metabolic syndrome. Our experiments findings show that BP-DF may use as a functional ingredient for preventing obesity, MetS, and intestinal microorganism imbalance. Therefore, BP-DF can be applied to the development and production of functional food, and can also be used as an important food functional ingredient, which can be added to various food, such as bread, noodles, baked goods, cakes, etc., to improve its nutritional value.

4.
J Mol Model ; 26(8): 198, 2020 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-32632503

RESUMO

In this study, the preparation of molecularly imprinted polymers for bilobalide (BBMIPs) was successfully achieved by bulk polymerization with methacrylamide (MAM), trimethylolpropane triacrylate (TMPTA), and acetonitrile (ACN) as functional monomer, cross-linker, and solvent, respectively. After Gaussian software simulation and single factor experiments, the prepared MIPs with a molar ratio of 1:4:15 for BB-MAM-TMPTA were systematically characterized. The hydrogen bonding interaction between BB and MAM was confirmed by a combination of FTIR and NMR analysis. Thermal gravimetric analysis results displayed that MIPs have excellent thermal stability under high temperature. Additionally, the average pore size and surface area of MIPs were found to be higher than those of NIPs through nitrogen adsorption results. The results of static adsorption and kinetic adsorption suggested that the adsorption equilibrium concentration was 0.6 mg/mL and the equilibrium time was 5 h, and the Langmuir and pseudo-second-order kinetic models were proven to fit with static and kinetic adsorption behaviors, respectively. Meanwhile, the selective adsorption study revealed that MIPs show high adsorption and great selectivity towards BB in comparison with other substances having similarly structure. MIPs also possessed a good performance on reusability, maintaining a high recovery rate after being reused 5 times. The application experiment further indicated that MIPs can effectively separate BB from low purity samples. Therefore, the prepared MIPs had a great potential for BB separation.

5.
Chem Commun (Camb) ; 56(63): 9016-9019, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32638737

RESUMO

A chiral metal-organic framework possessing an open amphiphilic channel is constructed from a dicarboxylate ligand derived from an amino acid and is shown to be an efficient and recyclable chiral solid adsorbent, which is capable of separating racemic secondary alcohols, epoxides, and ibuprofen with very high enantioselectivity.

6.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 36(1): 45-50, 2020 Jan 28.
Artigo em Chinês | MEDLINE | ID: mdl-32476372

RESUMO

OBJECTIVE: To investigate the probable roles of the novel C2H2 zinc finger transcription factor ZFP580 on all-transretinoic acid (ATRA)-regulated VSMCs migration and underlying mechanisms. METHODS: Rat aortic VSMCs were isolated, cultured and identified. VSMCs were treated with ATRA at the concentrations of 0, 5, 10 or 20 µmol/L for 24 hours. The migration ability of VSMCs was observed in each group and compared with control group which was treated by 0 µmol/L ATRA. The mRNA and protein expression levels of ZFP580 were detected by QPCR and Western blot. ZFP580 protein expression in VSMCs was detected under ATRA stimulation when ERK inhibitor PD98059 was used to inhibit the protein expression of ERK. Adenovirus transfection technology was used to obtain VSMCs with overexpression or low expression of ZFP580, and QPCR and Western blot were used to detect the mRNA and protein levels of MMP-2, MMP-9 and ZFP580. RESULTS: On the 10th day of VSMCs culture, immunofluorescence showed that SM22 alpha antibody, as a specific marker of smooth muscle cells, was positive. Compared to the control group, VSMCs migration was reduced by 32%, 43%, and 59% in the group of 5, 10, and 20 µmol/L ATRA pretreatment. Compared with the control group, VSMCs treated by 20 µmol/L ATRA reduced the cell migration by 49%, 36% and 22% at 24, 48 and 72 h. The mRNA and protein expression levels of ZFP580 were increased with the increase of ATRA stimulation solubility and the extension of stimulation time. ERK was increased significantly after 15 min of ATRA stimulation. Pretreatment with ERK inhibitor PD98059 (20 µmol/L) inhibited the expression of ERK protein and reduced the expression of ATRA-induced ZFP580 protein. Overexpression of ZFP580 inhibited the expressions of MMP-2 and MMP-9, whereas down-expression of ZFP580 promoted the expressions of MMP-2 and MMP-9. CONCLUSION: ATRA increased the expression of ZFP580 through the ERK signaling pathway, while ZFP580 was involved in ATRA's inhibition of VSMCs migration by affecting the expression of downstream MMP-2 and MMP-9.


Assuntos
Movimento Celular , Miócitos de Músculo Liso/citologia , Fatores de Transcrição/metabolismo , Tretinoína/farmacologia , Animais , Células Cultivadas , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Músculo Liso Vascular/citologia , Miócitos de Músculo Liso/efeitos dos fármacos , Ratos , Transdução de Sinais
7.
Aging (Albany NY) ; 12(8): 6586-6599, 2020 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-32330901

RESUMO

Radiotherapy is the major approach and is well tolerated in locally advanced esophageal squamous cell carcinoma (ESCC). And nowadays, no effective biological markers have been identified for predicting the prognosis of patients with ESCC. Platelet-derived growth factor (PDGF) is associated with a poor prognosis of various malignancies. The present study aimed to assess the effect of PDGF-BB on radiotherapeutic responses of ESCC and the underlying mechanisms of its roles in ESCC. Serum from 68 cases that received neoadjuvant or radical radiotherapy was obtained before and during radiotherapy. Gene expression analyses were validated by enzyme linked immunosorbent assay. The prognosis of patients with significantly reduced PDGF-BB was probably better than that of the others found in the progression-free survival and overall survival groups. Depletion of PDGFB significantly suppressed the proliferation, invasion and migration of cancer cells. Inhibiting PDGFB induced cellular apoptosis and promoted the sensitivity to ionizing radiation (IR). Furthermore, IR inhibited PDGF-BB-induced migration by blocking the PI3K/AKT pathway in ESCC cells. We found that the expression of PDGF-BB provided a possible model for predicting ESCC radiotherapy. It can also be used as a prognostic indicator for locally advanced ESCC that was treated by radiotherapy.

8.
Oncologist ; 2020 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-32342599

RESUMO

LESSONS LEARNED: Patient compliance with the oral dosage treatment was good, with no need for hospitalization. Patients with tracheal and esophageal fistulas can take crushed apatinib by nutrient tube, with the same bioavailability and efficacy. Apatinib may be an effective and safe second- or further-line treatment for advanced esophageal cancer. BACKGROUND: Apatinib is an inhibitor of vascular endothelial growth factor receptor-2 (VEGFR2), which is thought to play a role in esophageal cancer progression. Our goal was to evaluate the efficacy and safety of apatinib in patients with unresectable esophageal cancer and to examine whether VEGFR2 expression influenced the clinical response. METHODS: This single-arm, open-label, investigator-initiated phase II study enrolled patients with advanced squamous cell carcinoma (SCC) or adenocarcinoma of the esophagus or esophagogastric junction who were admitted to Tianjin Medical University Cancer Institute and Hospital between August 2017 and January 2019. Apatinib monotherapy (500 mg/day) was given orally or via an enteral tube until disease progression, unacceptable toxicity, withdrawal, or death. Patients were followed until treatment was discontinued or death. The main endpoints were tumor response, progression-free survival (PFS), overall survival (OS), and adverse events (AEs). RESULTS: Among 32 patients screened for inclusion, 30 were included in the safety and survival analyses (i.e., received apatinib), and 26 were included in the efficacy analysis (at least one imaging follow-up). Median follow-up time and exposure to apatinib were 5.34 months and 72 days, respectively. Among 26 patients included in the efficacy analysis, 2 had a partial response (PR; 7.7%) and 14 had stable disease (SD; 53.8%). The overall response rate (ORR) was 7.7%, and the disease control rate (DCR) was 61.5%. Median PFS and OS were 4.63 months (95% confidence interval, 2.11-7.16 months) and 6.57 months (4.90 months to not estimable), respectively. Fifteen patients (50.0%) experienced treatment-related AEs, most commonly hypertension (26.7%), diarrhea (20.0%), and hand-foot-skin reaction (10.0%). No patients had grade ≥4 treatment-related AEs. CONCLUSION: Apatinib was effective as second- or further-line treatment for advanced esophageal cancer.

9.
J Mol Cell Cardiol ; 142: 39-52, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32268148

RESUMO

Vascular calcification is a pathological process closely related to atherosclerosis, diabetic vascular diseases, vascular injury, hypertension, chronic kidney disease and aging. Lethal giant larvae 1 (LGL1) is known as a key regulator of cell polarity and plays an important role in tumorigenesis. However, whether LGL1 regulates vascular calcification remains unclear. In this study, we generated smooth muscle-specific LGL1 knockout (LGL1SMKO) mice by cross-breeding LGL1flox/flox mice with α-SMA-Cre mice. LGL1 level was significantly decreased during calcifying conditions. Overexpression of LGL1 restrained high phosphate-induced calcification in vascular smooth muscle cells (VSMCs). Mechanically, LGL1 could bind with high mobility group box 1 (HMGB1) and promote its degradation via the lysosomal pathway, thereby inhibiting calcification. Smooth muscle-specific deletion of LGL1 increased HMGB1 level and aggravated vitamin D3-induced vascular calcification, which was attenuated by an HMGB1 inhibitor. LGL1 may inhibit vascular calcification by preventing osteogenic differentiation via promoting HMGB1 degradation.

10.
Biomater Sci ; 8(8): 2318-2328, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32187239

RESUMO

In the past decade, the development of gene carriers has been key in enhancing gene therapy. Gene therapy is associated with not only the delivery process but also gene expression as a prominent role. Herein, for the purpose of achieving a novel breakthrough in gene therapy, we creatively proposed a "strengthened gene expression" idea beyond the range of improving the gene carrier. We constructed three types of gene delivery systems, namely, single-pZNF580 delivery system, single-pVEGF165 delivery system, and dual-gene delivery system. These systems possessed approximate same sizes (∼120 nm) and zeta potentials (∼+20 mV), which indicated negligible differences in their cellular uptake. Interestingly, we found that the gene expression of dual-gene groups significantly increased at the level of both mRNA and protein at least 2 times and 1.5 times as high as single-gene groups, respectively. This "1 + 1 > 2" expression effect benefited from the coordinated expression of the angiogenesis-related genes of ZNF580 and VEGF165. Furthermore, the coordinated effect was also confirmed in HUVEC activities such as an obviously enhanced proliferation and migration of the dual-gene group. Rationally, we further evaluated the effects of coordinated interactions on neovascularization. We observed that the statistic tube number of dual-gene groups was approximately 1.44 times as high as that of single-gene groups. More importantly, this enhanced angiogenesis induced by the coordinated expression was also demonstrated in an in vivo environment. Therefore, we believed that the enhanced gene therapy via the gene expression pathway could provide a creative viewpoint for the design of gene delivery system and therapy.

11.
J Mater Chem B ; 8(12): 2418-2430, 2020 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-32115589

RESUMO

Bioreducible cationic polymers have gained considerable attention in gene delivery due to their low cytotoxicity and high efficiency. In the present work, we reported a cationic polymer, poly(disulfide-l-lysine)-g-agmatine (denoted as SSL-AG), and evaluated its ability to transfer pEGFP-ZNF580 plasmid (pZNF580) into human umbilical vein endothelial cells (HUVECs). This SSL-AG polymeric carrier efficiently condensed pZNF580 into positively charged particles (<200 nm) through electrostatic interaction. This carrier also exhibited excellent buffering capacity in the physiological environment, good pDNA protection against enzymatic degradation and rapid pDNA release in a highly reducing environment mainly because of the responsive cleavage of disulfide bonds in the polymer backbone. The hemolysis assay and in vitro cytotoxicity assay suggested that the SSL-AG carrier and corresponding gene complexes possessed both good hemocompatibility and great cell viability in HUVECs. The cellular uptake of the SSL-AG/Cy5-oligonucleotide group was 3.6 times that of the poly(l-lysine)/Cy5-oligonucleotide group, and its mean fluorescence intensity value was even higher than that of the PEI 25 kDa/Cy5-oligonucleotide group. Further, the intracellular trafficking results demonstrated that the SSL-AG/Cy5-oligonucleotide complexes exhibited a high nucleus co-localization rate (CLR) value (36.0 ± 2.8%, 3.4 times that of the poly (l-lysine)/Cy5-oligonucleotide group, 1.6 times that of the poly(disulfide-l-lysine)-g-butylenediamine/Cy5-oligonucleotide group) at 24 h, while the endo/lysosomal CLR value was relatively low. This suggested that SSL-AG successfully delivered plasmid into HUVECs with high cellular uptake, rapid endosomal escape and efficient nuclear accumulation owing to the structural advantages of the bioreducible and agmatine groups. In vitro transfection assay also verified the enhanced transfection efficiency in the SSL-AG/pZNF580 group. Furthermore, the results of CCK-8, cell migration and in vitro/vivo angiogenesis assays revealed that pZNF580 delivered by SSL-AG could effectively enhance the proliferation, migration and vascularization of HUVECs. In a word, the SSL-AG polymer has great potential as a safe and efficient gene carrier for gene therapy.

12.
Arterioscler Thromb Vasc Biol ; 40(4): 943-957, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32075416

RESUMO

OBJECTIVE: HuR (human antigen R)-an RNA-binding protein-is involved in regulating mRNA stability by binding adenylate-uridylate-rich elements. This study explores the role of HuR in the regulation of smooth muscle contraction and blood pressure. Approach and Results: Vascular HuRSMKO (smooth muscle-specific HuR knockout) mice were generated by crossbreeding HuRflox/flox mice with α-SMA (α-smooth muscle actin)-Cre mice. As compared with CTR (control) mice, HuRSMKO mice showed hypertension and cardiac hypertrophy. HuR levels were decreased in aortas from hypertensive patients and SHRs (spontaneously hypertensive rats), and overexpression of HuR could lower the blood pressure of SHRs. Contractile response to vasoconstrictors was increased in mesenteric artery segments isolated from HuRSMKO mice. The functional abnormalities in HuRSMKO mice were attributed to decreased mRNA and protein levels of RGS (regulator of G-protein signaling) protein(s) RGS2, RGS4, and RGS5, which resulted in increased intracellular calcium increase. Consistently, the degree of intracellular calcium ion increase in HuR-deficient smooth muscle cells was reduced by overexpression of RGS2, RGS4, or RGS5. Finally, administration of RGS2 and RGS5 reversed the elevated blood pressure in HuRSMKO mice. CONCLUSIONS: Our findings indicate that HuR regulates vascular smooth muscle contraction and maintains blood pressure by modulating RGS expression.


Assuntos
Pressão Sanguínea/fisiologia , Proteína Semelhante a ELAV 1/fisiologia , Hipertensão/fisiopatologia , Músculo Liso Vascular/fisiologia , Vasoconstrição , Animais , Cálcio/metabolismo , Expressão Gênica , Humanos , Masculino , Camundongos Knockout , Proteínas RGS/genética , RNA Mensageiro/metabolismo , Ratos Endogâmicos SHR , Ratos Wistar
13.
BMC Cancer ; 20(1): 130, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32070309

RESUMO

BACKGROUND: Preoperative chemoradiotherapy (CRT) followed by surgery is the most common approach for patients with resectable esophageal cancer. Nevertheless, considerable numbers of esophageal-cancer patients undergo surgery as the first treatment. The benefit of neoadjuvant therapy might only be for patients with a pathologic complete response, so stratified research is necessary. Postoperative treatments have important roles because of the poor survival rates of patients with stage-IIB/III disease treated with resection alone. Five-year survival of patients with stage-IIB/III thoracic esophageal squamous cell carcinoma (TESCC) after surgery is 20.0-28.4%, and locoregional lymph-node metastases are the main cause of failure. Several retrospective studies have shown that postoperative radiotherapy (PORT) and postoperative chemoradiotherapy (POCRT) after radical esophagectomy for esophageal carcinoma with positive lymph-node metastases and stage-III disease can decrease locoregional recurrence and increase overall survival (OS). Using intensity-modulated RT, PORT reduces locoregional recurrence further. However, the rate of distant metastases increases to 30.7%. Hence, chemotherapy may be vital for these patients. Therefore, a prospective randomized controlled trial (RCT) is needed to evaluate the value of PORT and concurrent POCRT in comparison with surgery alone (SA) for esophageal cancer. METHOD: This will be a phase-II/III RCT. The patients with pathologic stage-IIB/III esophageal squamous cell carcinoma will receive concurrent POCRT or PORT after radical esophagectomy compared with those who have SA. A total of 120 patients in each group will be recruited. POCRT patients will be 50.4 Gy concurrent with paclitaxel (135-150 mg/m2) plus cisplatin or nedaplatin (50-75 mg/m2) treatment every 28 days. Two cycles will be required for concurrent chemotherapy. The prescription dose will be 54 Gy for PORT. The primary endpoint will be disease-free survival (DFS). The secondary endpoint will be OS. Other pre-specified outcome measures will be the proportion of patients who complete treatment, toxicity, and out-of-field regional recurrence rate between PORT and POCRT. DISCUSSION: This prospective RCT will provide high-level evidence for postoperative adjuvant treatment of pathologic stage-IIB/III esophageal squamous cell carcinoma. TRIAL REGISTRATION: clinicaltrials.gov (NCT02279134). Registered on October 26, 2014.

14.
J Sep Sci ; 43(2): 514-523, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31642160

RESUMO

Ginkgolide B is in great demand worldwide on account of its extensive and excellent pharmacological effects, however, it is difficult to separate and purify ginkgolide B. In this study, ginkgolide B molecularly imprinted polymers were prepared by combining software simulation and molecular imprinting technique, and its characterization and adsorption performed evaluation were performed to understand the adsorption behavior of the polymers. The adsorption equilibrium concentration of molecularly imprinted polymers was 0.70 mg/mL, and the adsorption equilibrium time was 4 h. Meanwhile, the adsorption isotherm of the polymers for ginkgolide B fitted well with the Langmuir model, and the adsorption kinetics was in line with the pseudo-second-order kinetics. In contrast, the adsorption capacity of molecularly imprinted polymers on ginkgolide B was higher than that of non-molecular imprinted polymers, with better selectivity and better adsorption after repeated use for six times. The application experiments showed that molecular imprinted polymers have a good adsorption effect in low purity samples. Therefore, the polymers reported herein can be expected to apply in the adsorption and separation of ginkgolide B samples.

15.
Clin Chim Acta ; 502: 55-65, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31821791

RESUMO

BACKGROUND: Urinary proteins could be useful as markers for the detection of non-small-cell lung cancer (NSCLC). We investigated the levels of two different proteins in urine samples from NSCLC patients and assessed their diagnostic value. METHODS: Urinary plasminogen (PLG) and fibrinogen gamma chain (FGG) levels in 112 NSCLC patients and 197 controls were detected using enzyme linked immunosorbent assay (ELISA). The expression of FGG and PLG in 20 NSCLC tissues and paired adjacent non-tumour tissues were detected through immunohistochemistry. The diagnostic value of FGG and PLG for NSCLC was evaluated through a receiver operating characteristic curve (ROC). RESULTS: PLG and FGG were significantly elevated in NSCLC tissues vs paired adjacent non-tumour tissues (p = 0.000) and in urinary samples from NSCLC patients vs healthy controls (p = 0.000). The expression level of PLG in urinary samples was related only to the histological type (p = 0.001). Further, ROC curve analysis revealed that PLG, FGG, and their combination could distinguish NSCLC and its subtypes from healthy controls with an AUC ranging from 0.827 to 0. 947. By comparing urine samples with matching plasma CEA from NSCLC stage I-IV patients (n = 81) and healthy controls (n = 31), the combination of CEA with PLG or FGG showed that the AUC was 0.889 and 0.806, respectively, which is superior to a single biomarker alone. CONCLUSIONS: These two urinary proteins could serve as potential markers for the diagnosis of NSCLC.

16.
J Gerontol B Psychol Sci Soc Sci ; 75(5): 1042-1052, 2020 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-30698810

RESUMO

OBJECTIVES: This investigation examined predictors of monetary transfers made by grandparents for the benefit of their grandchildren in rural China. Predictors included family factors related to financial supply (remittances received from the parents of grandchildren), household demand (living in a skipped-generation household), and patrilineal culture (targeting sons and grandsons). METHOD: The 2015 wave of the Longitudinal Study of Older Adults in Anhui Province was used to study financial transfers made by 831 grandparents to grandchildren in the families of 1,633 parents. Two-part random-effects regression was used to predict whether a transfer was made and the value of transfers, given that one occurred. RESULTS: Grandparents provided higher value transfers to grandchildren whose parents provided greater remittances and with whom they coresided in skipped-generation households. The likelihood of making a transfer fully followed the male lineage, and was greatest to grandson-only families in which parents were first-born sons. DISCUSSION: Results show that economic, household, and cultural factors are independently associated with the largesse of grandparents. We conclude that grandparents' economic contributions to grandchildren in rural China are shaped by family demands in a highly mobile society, intergenerational interdependence, and a persistent patrilineal gender system that reaches to the level of grandchildren.

17.
Food Chem Toxicol ; 135: 110933, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31682930

RESUMO

Chelerythrine (CHE), a benzophenanthridine alkaloid, is usually used as a nutritional and functional additive in variety of health foods. However, it should be paid enough attention because of its potential toxicity to human health. In this work, the binding mechanism of CHE with bovine serum albumin (BSA) was systematically investigated with spectroscopic approaches. The results showed that the mixture of BSA with CHE could spontaneously cause the formation of BSA-CHE complex through electrostatic interaction under simulative physiological conditions (0.01 mol L-1 Tris-HCl, 0.015 mol L-1 NaCl, pH = 7.4). Site marker competitive displacement experiments exhibited that CHE was primarily bound to the hydrophobic pocket of the site II (subdomain IIIA) of BSA. It has been reported that the binding of small functional molecules to serum albumins remarkably impacts their absorption, distribution, metabolism, conformation, and excretion features. Therefore, this study might be helpful for human to have an in-depth understanding of the biological effect of CHE in vivo and guide human to take it safely and reasonably.


Assuntos
Benzofenantridinas/metabolismo , Soroalbumina Bovina/metabolismo , Animais , Sítios de Ligação , Bovinos , Dicroísmo Circular , Ligação Proteica , Conformação Proteica em alfa-Hélice/efeitos dos fármacos , Espectrometria de Fluorescência , Termodinâmica
18.
Biochim Biophys Acta Mol Basis Dis ; 1866(3): 165649, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31870714

RESUMO

Genome-wide changes in gene translational efficiency during the development of heart failure are poorly understood. We tested the hypothesis that aberrant changes in translational efficiency of cardiac genes are associated with the development of myocyte decompensation in response to persistent stress stimuli. We demonstrated that chronic pressure overload in mice resulted in a genome-wide reprogramming of translational efficiency, with >50% of the translatome exhibiting decreased translational efficiencies during the transition from myocardial compensation to decompensation. Importantly, these translationally repressed genes included those involved in angiogenesis and energy metabolism. Moreover, we showed that the stress-induced translational reprogramming was accompanied by persistent activation of the eukaryotic initiation factor 2α (eIF2α)-mediated stress response pathway. Counteracting the endogenous eIF2α functions by cardiac-specific overexpression of an eIF2α-S51A mutant ameliorated the development of myocyte decompensation, with concomitant improvements in translation of cardiac functional genes and increases in angiogenic responses. These data suggest that the mismatch between transcription and translation of the cardiac genes with essential functions may represent a novel molecular mechanism underlying the development of myocyte decompensation in response to chronic stress stimuli, and the eIF2α pathway may be a viable therapeutic target for recovering the optimal translation of the repressed cardiac genes.


Assuntos
Reprogramação Celular/genética , Insuficiência Cardíaca/genética , Miócitos Cardíacos/fisiologia , Biossíntese de Proteínas/genética , Animais , Fator de Iniciação 2 em Eucariotos/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais/genética
19.
Food Chem Toxicol ; 134: 110867, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31586655

RESUMO

Ellagic acid (EA), a natural plant polyphenol, is usually used as a functional additive in variety of health foods. However, the potential toxicity of EA to human health should be paid enough attention. To clarify its biological toxicity in vivo, this study explored the binding mechanism of EA with bovine serum albumin (BSA) by means of spectroscopic approaches and molecular docking insimulative physiological conditions. The results showed that the mixture of BSA with EA could spontaneously cause the formation of BSA-EA complex through electrostatic interaction under simulative physiological conditions (0.01 mol·L-1Tris-HCl, 0.015 mol L-1 NaCl, pH = 7.4). Molecular docking experiments revealed that EA was primarily bound to the hydrophobic pocket of the site I (subdomain IIA) of BSA. It has been reported that the binding of small functional molecules to serum albumins remarkably impacts their absorption, distribution, metabolism, and excretion features. Therefore, this study might be helpful for human to have an in-depth understanding of the biological effect of EA in vivo and guide human to take it safely and reasonably.


Assuntos
Ácido Elágico/metabolismo , Aditivos Alimentares/metabolismo , Soroalbumina Bovina/metabolismo , Sítios de Ligação , Ligação Proteica , Espectrometria de Fluorescência , Espectrofotometria Ultravioleta
20.
Cancer Manag Res ; 11: 8285-8294, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31571986

RESUMO

Purpose: To evaluate and analyze the efficacy and prognostic factors of intensity-modulated radiotherapy in 250 patients with cervical and upper esophageal carcinoma. Patients and methods: From September 2009 to September 2016, we retrospectively analyzed 250 patients with cervical and upper esophageal carcinoma treated with intensity-modulated radiotherapy (IMRT). In our study, all patients received IMRT, 54 patients with cervical esophageal carcinoma and 196 patients with upper esophageal carcinoma. Treatment response, survival status and failure modes of treatment were observed, and prognostic factors were analyzed. Results: The median survival time was 22.60 months and 3-year survival rate was 42%. The median progress-free survival time was 14.52 months and 3-year progress-free survival rate was 29.3%. The median survival time and the median progress-free survival time for cervical esophageal carcinoma were 20.40 and 15.15 months, respectively. The median survival time and the median progress-free survival time for upper esophageal carcinoma were 25.80 and 14.52 months, respectively (P>0.05). The significant clinical factors associated with survival were patient age, radiotherapy dose and T stages (P<0.05). Radiotherapy dose and concurrent chemoradiotherapy were the significant clinical factors related to progression-free survival (P<0.05). Recurrence appeared in 55.2% patients, including local recurrence in 22.40%, region relapse in 10.40% and distant metastasis in 12.40%. Local recurrence was the main mode of treatment failure. During treatment, the main treatment-related acute toxicity was leukocytopenia and anemia. Conclusion: In this study, IMRT demonstrated clinical benefit and well-tolerated toxicity in patients with cervical and upper esophageal carcinoma.

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