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1.
J Ethnopharmacol ; 265: 113295, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32841701

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Scutellariabarbata D. Don extraction (SBE), a traditional Chinese medicine, has been proved effective against various malignant disorders in clinics with tolerable side-effects when administered alone or in combination with conventional chemotherapeutic regimens. AIM OF THIS STUDY: Multi-drug resistance of cancer is attributed to existence of cancer stemness-prone cells that harbor aberrantly high activation of Sonic Hedgehog (SHH) cascade. Our previous study has demonstrated that SBE sensitized non-small cell lung cancer (NSCLC) cells to Cisplatin (DDP) treatment by downregulating SHH pathway. Yet, whether SBE could prohibit proliferation of cancer stemness-prone cells and its underlying molecular mechanisms remain to be investigated. In this article, we further investigated intervention of SBE on NSCLC cell stemness-associated phenotypes and its potential mode of action. MATERIALS AND METHODS: CCK-8 and clonal formation detection were used to measure the anti-proliferative potency of SBE against NSCLC and normal epithelial cells. Sphere formation assay and RQ-PCR were used to detect proliferation of cancer stemness cells and associated marker expression upon SBE incubation. Mechanistically, DARTS-WB and SPR were used to unveil binding target of SBE. Immunodeficient mice were implanted with patient derived tumor bulk for in vivo validation of anti-cancer effect of SBE. RESULTS: SBE selectively attenuated proliferation and stemness-like phenotypes of NSCLC cells rather than bronchial normal epithelial cells. Drug-protein interaction analysis revealed that SBE could directly bind with stem cell-specific transcription factor sex determining region Y-box 2 (SOX2) and interfere with the SOX2/SMO/GLI1 positive loop. In vivo assay using patient-derived xenografts (PDXs) model further proved that SBE diminished tumor growth and SOX2 expression in vivo. CONCLUSION: Our data indicate that SBE represses stemness-related features of NSCLC cells via targeting SOX2 and may serve as an alternative therapeutic option for clinic treatment.

2.
Food Chem ; 337: 127802, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32795851

RESUMO

Deoxynivalenol (DON) and T-2 toxin are major trichothecenes contaminated in cereals, which might bring harmful effects to humans. In this research, mixed anti-DON and anti-T-2 mAb were used for multiple immunoaffinity columns (mIACs) preparation. Under the optimal conditions, column capacities were tested at 1280 ng/mL for DON and 1160 ng/mL for T-2 toxin. Regeneration investigation showed mIACs capacities were over 510 ng/mL for DON and 440 ng/mL for T-2 toxin in 10 recycle usages. Good performances were obtained when applying mIACs purification coupled UHPLC-MS/MS for spiked samples with limit of detection at 3-13 µg/kg and mean recoveries at 79.0-97.6%. Applying to estimate the exposure of DON and T-2 toxin in commercial samples, maize samples were 100% DON positive and rice samples were 40% DON positive while T-2 toxin was negative in all tested samples. The proposed method is reliable and suitable for monitoring DON and T-2 toxin in cereal samples.

3.
Biomaterials ; 264: 120386, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32979656

RESUMO

The precise treatment of drug-resistant deep bacterial infections remains a huge challenge in clinic. Herein, a polymer-peptide-porphyrin conjugate (PPPC), which can be real-time monitored in infectious site, is developed for accurate and deep sonodynamic therapy (SDT) based on "in vivo self-assembly" strategy. The PPPC contains four moieties, i.e., a hyperbranched polymer backbone, a self-assembled peptide linked with an enzyme-cleavable peptide-poly (ethylene glycol) terminal, a bacterial targeting peptide, and a porphyrin sonosensitizer (MnTCPP) segment. Once PPPC nanoparticles reach the infectious area, the protecting PEG layers are removed due to the over-expressed gelatinase, leading to the secondary assembly into large nanoaggregates and resultant enhanced accumulation of sonosensitizer. The nanoaggregates exhibit enhanced interaction with bacterial membrane and decrease the minimum inhibitory concentration (MIC) significantly. Meanwhile, compared with free MnTCPP, the concentration of which can not be accurately quantified, the accumulation amount of MnTCPP in PPPCs at infectious site can be in situ monitored by magnetic resonance imaging (MRI) using T1 combined with T2. When the concentration of PPPC-1 reaches MIC, the drug-resistant bacterial infection area is exposed to ultrasound irradiation, causing the precise and efficient elimination of bacteria. Therefore, the MRI-guided SDT system shows extraordinary tissue penetration depth, drug concentration monitoring, morphology-transformation induced accumulation and improved treatment capacity toward drug-resistant bacteria.

4.
J Cell Physiol ; 236(2): 889-899, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33020901

RESUMO

Long intergenic noncoding RNAs (lincRNAs) play a vital role in the occurrence and progression of cancer. The mechanism of lincRNAs in colorectal cancer (CRC) has not been fully elucidated. In this context, an integrated comparative long noncoding RNA (lncRNA) microarray technology was used to determine the expression profile of lncRNAs in CRC. The roles of LINC00908 are unclear. We found that LINC00908 was significantly upregulated in CRC. Inhibition of LINC00908 resulted in reduced cell proliferation and G1 cell cycle arrest, which was mediated by cyclin D1, cyclin-dependent kinase 4, and phosphorylated retinoblastoma. Moreover, inhibition of LINC00908-induced apoptosis through the intrinsic apoptosis signaling pathway, as shown by the activation of caspase-9 and caspase-3. Mechanistically, miR-143-3p directly bound to LINC00908. miR-143-3p expression was negatively correlated with LINC00908 expression in CRC tissue. Functional experiments revealed opposing roles for miR-143-3p and LINC00908, suggesting that LINC00908 negatively regulates miR-143-3p. Mechanistically, miR-143-3p directly targets LINC00908. The KLF5 inhibitor ML264 affected proliferation and apoptosis, indicating that LINC00908 may act as a competing endogenous RNA to facilitate the expression of the miR-143-3p target gene KLF5. Thus, LINC00908 has an important proliferative and antiapoptotic role in CRC by regulating the cell cycle and intrinsic apoptosis. LINC00908 could be a potential biomarker and a new therapeutic target for CRC.

6.
Chemosphere ; 262: 128390, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33182154

RESUMO

Hydroxylamine (HA) driven advanced oxidation processes (HAOPs) for water treatment have attracted extensive attention due to the acceleration of reactive intermediates generation and the improvement on the elimination effectiveness of target contaminants. In this review, HAOPs were categorized into three parts: (1) direct reaction of HA with oxidants (e.g., hydrogen peroxide (H2O2), peroxymonosulfate (PMS), ozone (O3), ferrate (Fe(VI)), periodate (IO4-)); (2) HA driven homogeneous Fenton/Fenton-like system (Fe(II)/peroxide/HA system, Cu(II)/O2/HA system, Cu(II)/peroxide/HA system, Ce(IV)/H2O2/HA system); (3) HA driven heterogeneous Fe/Cu-Fenton/Fenton-like system (iron-bearing material/peroxide/HA system, copper-bearing material/peroxide/HA system, bimetallic composite/peroxide/HA system). Degradation efficiency of the target pollutant, reactive intermediates, and effective pH range of various HAOPs were summarized. Further, corresponding reaction mechanism was elaborated. For the direct reaction of HA with oxidants, improvement of pollutants degradation was achieved through the generation of secondary reactive intermediates which had higher reactivity compared with the parent oxidant. For HA driven homogeneous and heterogeneous Fe/Cu-Fenton/Fenton-like system, improvement of pollutants degradation was achieved mainly via the acceleration of redox cycle of Fe(III)/Fe(II) or Cu(II)/Cu(I) and subsequent generation of reactive intermediates, which avoided the drawbacks of classical Fenton/Fenton-like system. In addition, HA driven homogeneous Fe/Cu-Fenton/Fenton-like system with heterogeneous counterpart were compared. Further, formation of oxidation products from HA in various HAOPs was summarized. Finally, the challenges and prospects in this field were discussed.


Assuntos
Hidroxilamina/química , Purificação da Água/métodos , Cobre , Compostos Férricos , Peróxido de Hidrogênio , Hidroxilaminas , Ferro , Oxidantes , Oxirredução , Peróxidos , Água , Poluentes Químicos da Água
7.
Prog Lipid Res ; : 101072, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33188800

RESUMO

In plants, hypoxia (low-oxygen stress) is induced by soil waterlogging or submergence and this major abiotic stress has detrimental effects on plant growth, development, distribution, and productivity. To survive low-oxygen stress, plants have evolved a set of morphological, physiological, and biochemical adaptations. These adaptations integrate metabolic acclimation and signaling networks allowing plants to endure or escape from low-oxygen environments by altering their metabolism and growth. Lipids are ubiquitously involved in regulating plant responses to hypoxia and post-hypoxic reoxygenation. In particular, the polyunsaturation of long-chain acyl-CoAs regulates hypoxia sensing in plants by modulating acyl-CoA-binding protein-Group VII ethylene response factor dynamics. Moreover, unsaturated very-long-chain ceramide species protect plants from hypoxia-induced cellular damage by regulating the kinase activity of CONSTITUTIVE TRIPLE RESPONSE1 in the ethylene signaling pathway. Finally, the oxylipin jasmonate specifically regulates plant responses to reoxygenation stress by transcriptionally modulating antioxidant biosynthesis. Here we provide an overview of the roles of lipid remodeling and signaling in plant responses to hypoxia/reoxygenation and their effects on the downstream events affecting plant survival. In addition, we highlight the key remaining challenges in this important field.

8.
Reprod Biol Endocrinol ; 18(1): 107, 2020 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-33160385

RESUMO

BACKGROUND: Ovarian teratoma-associated anti-N-methyl-D-aspartate receptor encephalitis (NMDAR-E) is a severe autoimmune neurological disorder, and the influence of teratoma-induced autoantibodies on the pathogenesis remains unclear. METHODS: Ovarian teratoma tissues were collected from teratoma patients with and without NMDAR-E. Proteins were extracted and then analyzed using iTRAQ-coupled LC-MS/MS, which was followed by bioinformatics analysis. Candidate proteins were verified by Western blotting and immunohistochemistry. RESULTS: In total, 36 differentially expressed proteins (DEPs) were identified between the control group and NMDAR-E group, and the bioinformatics analysis revealed that the DEPs were mainly involved in immune-related pathways, especially HLA-A and HLA-DRB1. The western blotting results for HLA-A and HLA-DRB1 were consistent with the results of the iTRAQ analysis. Additionally, the immunohistochemical data revealed that the aggregation of HLA-A (+) and HLA-DRB1 (+) cells was more apparent in the teratoma tissues of NMDAR-E patients compared with that in the tissues of controls. CONCLUSION: Our investigation indicated that HLA-A and HLA-DRB1 might be involved in mediating ovarian teratoma-associated NMDAR-E. These findings provide new insights into the pathophysiological mechanisms and provide information for the functional exploration of proteins in the future.

9.
Mol Neurobiol ; 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33185843

RESUMO

The original version of this article unfortunately has errors and should be corrected.

10.
Food Funct ; 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33179663

RESUMO

Antibiotics are the most commonly used clinical drugs for anti-infection, but they can also destroy normal microorganisms and cause intestinal barrier dysfunction. To elucidate the effects and mechanism of a water-soluble polysaccharide from Fagopyrum esculentum Moench bee pollen (WFPP) on intestinal barrier integrity in antibiotic-treated mice, BALB/c mice were exposed to a broad-spectrum antibiotic (ceftriaxone) or not (control), and were administered low-, medium- and high-dose WFFP (100 mg kg-1, 200 mg kg-1 and 400 mg kg-1, respectively) daily by oral gavage for 3 weeks. Mice treated with ceftriaxone displayed symptoms of growth retardation, atrophy of immune organs including thymus and spleen, increased gut permeability, and intestinal barrier damage, which were restored after intervention with WFFP at different doses. Moreover, the beneficial effects of WFFP were closely associated with enhanced intestinal sIgA secretion and reduced inflammatory response. Furthermore 16S rDNA gene sequencing revealed that WFPP elevated microbial diversity and richness and changed the community structure, therefore, alleviating microbiota dysbiosis caused by ceftriaxone. Interestingly, WFPP could modulate the abundance of sIgA secretion-related bacteria (e.g. Proteobacteria) and inflammation-related bacteria (e.g. Enterococcus). Therefore, WFPP can relieve antibiotic-induced microbiota dysbiosis to improve intestinal barrier integrity by increasing intestinal sIgA secretion and inhibiting inflammation.

11.
Brain Res ; : 147185, 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33129805

RESUMO

The combined use of two or more different drugs can better promote nerve recovery and its prognosis for treatment of stroke. The salvianolate lyophilized injection (SLI) and Xueshuantong Injection (XST) are two standardized Chinese medicine injections which have been widely used in the treatment of cerebrovascular diseases. Salvianolic acid B (Sal B) and Notoginsenoside R1 (NR1) is respectively one of the active constituents of SLI and XST, which have certain effects on stroke. In this study, we established a co-culture of endothelial cells and pericytes for oxygen-glucose deprivation/reperfusion (OGD/R) injury model to study the effects of SLI and Sal B or XST and NR1 alone, or with their combinations (1S1X) in regulation of BBB function. The results showed that compared with the OGD/R group, treatment with SLI, XST and SalB and NR1 can significantly increase the TEER, reduce the permeability of Na-Flu, enhance the expression of tight junctions (TJs) between cells, and stabilize the basement membrane (BM) composition. In addition, the combination of 1S1X is superior to the XST or SLI alone in enhancing the TJs between cells and stabilizing the BM. And the active components SalB and NR1 can play a strong role in these two aspects, even with the whole effects. Furthermore, the study showed that XST, Sal B and NR1 increases in Ang-1and Tie2, while decrease in Ang-2 and VEGF protein expressions. Overall, these findings suggest that SLI combined with XST (1X1S) has protective effects on co-culture of endothelial cells and pericytes after OGD/R. Moreover, its protective effect might be associated with increase of TJs and BMs through activation of Ang/Tie-2 system signaling pathway.

12.
Radiology ; : 201416, 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33170102

RESUMO

Background Accurate differentiation of stage T0-T1 rectal tumors from stage T2 rectal tumors facilitates the selection of appropriate surgical treatment. MRI is a recommended technique for local staging, but its ability to distinguish T1 from T2 tumors is poor. Purpose To explore the value of a submucosal enhancing stripe (SES), an uninterrupted enhancing band between the rectal tumor and the muscular layer on contrast material-enhanced T1-weighted images, as a potential imaging feature to differentiate T0-T1 from T2 rectal tumors. Materials and Methods This retrospective study included patients with pT0-T1 and pT2 rectal tumors who underwent pretreatment MRI and rectal tumor resection between January 2012 and November 2019. Two radiologists independently evaluated tumor characteristics (SES; status of muscularis propria [SMP]; and tumor shape, location, and size) at MRI. The associations of clinical and imaging characteristics with stage T0-T1 or T2 tumors were assessed, ß values were calculated, and predictive models were built. The diagnostic accuracies for the differentiation of T0-T1 tumors from T2 tumors with SES and SMP were compared. Results Data from 431 patients (mean age, 60 years ± 10 [standard deviation]; 261 men) were evaluated. SES (ß = 3.9; 95% CI: 3.1, 4.7; P < .001), SMP (ß = 1.3; 95% CI: 0.7, 1.9; P < .001), and carpetlike shape (ß = 1.6; 95% CI: 0.5, 2.8; P = .01) were independent factors distinguishing T0-T1 tumors from T2 tumors. The diagnostic accuracy was 87% (95% CI: 84, 90; 376 of 431) for SES and 67% (95% CI: 63, 72; 290 of 431) for SMP (P < .001). Conclusion Submucosal enhancing stripe (SES) at contrasted-enhanced MRI, status of muscularis propria (SMP) on T2-weighted images, and tumor shape can serve as independent imaging features to differentiate stage T0-T1 rectal tumors from stage T2 rectal tumors. Moreover, SES is a more accurate feature than is SMP. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Turkbey in this issue.

13.
Food Chem ; : 128351, 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33172751

RESUMO

This study was aimed to establish a quantitative function between spectral reflectance values and metmyoglobin (MetMb) content in Tan mutton during refrigeration. Near-infrared hyperspectral data combined with generalized two-dimensional correlation spectroscopy (G2D-COS) method to identify characteristic bands and investigate the sequence of chemical waveband changes. Characteristic wavebands identified by G2D-COS analysis had the best performance in predicting the content of MetMb, with a high R2p of 0.849, a low RMSEP of 2.695 and a high RPD of 2.786. The results showed that the G2D-COS may be a powerful tool for describing intensity changes of MetMb band. The partial least square regression method was used to develop the relationships between the spectral values and MetMb content in Tan mutton meat for predicting MetMb content. This study has provided a convenient and rapid non-destructive quantitative method for assessing the color of Tan mutton meat.

14.
J Clin Lipidol ; 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33144084

RESUMO

BACKGROUND: Excess maternal triglyceride (mTG) exposure during early or late pregnancy increases risks of adverse pregnancy outcomes. However, it is inconclusive whether persistently high maternal triglyceride during whole pregnancy has more negative associations. OBJECTIVE: To explore whether persistently high maternal triglyceride (mTG) levels from early to late pregnancy further increases the risk of adverse pregnancy outcomes. METHODS: We included 12,715 women who had a singleton birth and who underwent routine serum lipid screenings in both early (9-13 weeks) and late (28-42 weeks) pregnancy during May 2018 to July 2019 in a university-based maternity center. Risks for gestational diabetes mellitus (GDM), preeclampsia, preterm delivery, small/large for gestational age (LGA) were estimated. RESULTS: Elevated mTG levels during early pregnancy were associated with increased risks of preterm delivery (AOR, 1.52; 95% CI, 1.21 to 1.90), preeclampsia (1.75; 1.29 to 2.36), gestational diabetes mellitus (1.95; 1.69 to 2.25), and LGA (1.28; 1.12 to 1.46). Compared with those with low mTG levels both in the 1st and 3rd trimesters, persistently high mTG levels increased the risks of preeclampsia (2.53; 1.66 to 3.84), GDM (1.97; 1.57 to 2.47), and LGA (1.68; 1.37 to 2.07). However, persistently high mTG levels only slightly increased risk of LGA when compared with high mTG levels during the 1st trimester alone (1.34, 1.01 to 1.77). CONCLUSIONS: Elevated mTG levels during early pregnancy not in late pregnancy could be the crucial risk factor associated with adverse pregnancy outcomes. These results suggest the importance of lipid screenings and preventions during early pregnancy, which may help to improve pregnancy outcomes.

15.
Transbound Emerg Dis ; 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33155433

RESUMO

In this study, we introduce a vulnerability index to measure the regional ASF epidemic and present the ASF severity ratings of the 31 provinces of mainland China. The index is defined based on the data from the investigation, national statistical yearbook and reports. The data to be used includes pig breeding, financial resources, human resources, epidemic information of ASF and price fluctuation from the 31 provinces. Then we use the data envelopment analysis (DEA) method to define the vulnerability index, the relative severity values for each region which quantitatively reflect the damage degree caused by the epidemic of ASF. The method allows us to provide a systematic classification for the regional vulnerability level of ASF in China. Using this index, we find that the vulnerability of the whole country is at a high level, and there is no regional aggregation phenomenon. The vulnerability level of the 31 provinces are quite different and the provinces with high vulnerability level are dispersive geographically. For the five major prevention and control zones for ASF in China, the northern region has the highest vulnerability level, while the eastern zoon level is the lowest.

16.
Trials ; 21(1): 944, 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33225982

RESUMO

BACKGROUND: Although evidence had demonstrated the effectiveness of smartphone apps in diabetes care, the majority of apps had been developed for type 2 diabetes mellitus (T2DM) patients and targeted at populations outside of China. The effects of applying a smartphone app with structured education on glycemic control in type 1 diabetes mellitus (T1DM) are unclear. A digital, culturally tailored structured education program was developed in a smartphone app (Yi tang yun qiao) to provide an automated, individualized education program aimed at improving self-management skills in patients with T1DM in China. This trial aims to investigate the effectiveness of this smartphone app among Chinese T1DM patients. METHODS AND ANALYSIS: This single-blinded, 24-week, parallel-group randomized controlled trial of a smartphone app versus routine care will be conducted in Changsha, China. We plan to recruit 138 patients with T1DM who will be randomly allocated into the intervention group (automated, individualized education through an app) or routine care group. The intervention will last for 24 weeks. The primary outcome will be the change in glycated hemoglobin (HbA1c) from baseline to week 24. The secondary outcomes will include time in range, fasting blood glucose, levels of serum triglycerides and cholesterol, blood pressure, body mass index, quality of life, diabetes self-care activities, diabetes self-efficacy, depression, anxiety, and patient satisfaction. Adverse events will be formally documented. Data analysis will be conducted using the intention-to-treat principle with appropriate univariate and multivariate methods. Missing data will be imputed with a multiple imputation method under the "missing at random" assumption. DISCUSSION: This trial will investigate the effectiveness of an app-based automated structured education intervention for Chinese patients with T1DM. If the intervention is effective, this study will provide a strategy that satisfies the need for effective lifelong diabetes care to reduce the disease burden and related complications resulting from T1DM. TRIAL REGISTRATION: ClinicalTrials.gov NCT04016987 . Registered on 29 October 2019.

17.
Aging (Albany NY) ; 122020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33226370

RESUMO

In this meta-analysis, we systematically investigated the correlation between single nucleotide polymorphisms (SNPs) and pancreatic cancer (PC) risk. We searched PubMed, Network Science, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), China Science and Technology Periodical Database (VIP), and Wanfang databases up to January 2020 for studies on PC risk-associated SNPs. We identified 45 case-control studies (36,360 PC patients and 54,752 non-cancer individuals) relating to investigations of 27 genes and 54 SNPs for this meta-analysis. Direct meta-analysis followed by network meta-analysis and Thakkinstian algorithm analysis showed that homozygous genetic models for CTLA-4 rs231775 (OR =0.326; 95% CI: 0.218-0.488) and VDR rs2228570 (OR = 1.976; 95% CI: 1.496-2.611) and additive gene model for TP53 rs9895829 (OR = 1.231; 95% CI: 1.143-1.326) were significantly associated with PC risk. TP53 rs9895829 was the most optimal SNP for diagnosing PC susceptibility with a false positive report probability < 0.2 at a stringent prior probability value of 0.00001. This systematic review and meta-analysis suggests that TP53 rs9895829, VDR rs2228570, and CTLA-4 rs231775 are significantly associated with PC risk. We also demonstrate that TP53 rs9895829 is a potential diagnostic biomarker for estimating PC risk.

18.
Drug Des Devel Ther ; 14: 4519-4531, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33149550

RESUMO

Purpose: Lung cancer remains the leading cancer-associated deaths worldwide. Cisplatin (CIS) was often used in combination with other drugs for the treatment of non-small cell lung cancer (NSCLC). Prodrug is an effective strategy to improve the efficiency of drugs and reduce the toxicity. The aim of this study was to prepare and characterize CIS prodrug, vinorelbine (VNR), and all-trans retinoic acid (ATRA) co-delivered multi-layered nano-platform, evaluating their antitumor activity in vitro and in vivo. Methods: Cisplatin prodrug (CISP) was synthesized. A multi-layered nano-platform contained CISP, VNR and ATRA were prepared and named CISP/VNR/ATRA MLNP. The physicochemical properties of CISP/VNR/ATRA MLNP were investigated. In vitro cytotoxicity against CIS-resistant NSCLC cells (A549/CIS cells) and Human normal lung epithelial cells (BEAS-2B cells) was investigated, and in vivo anti-tumor efficiency was evaluated on mice bearing A549/CIS cells xenografts. Results: CISP/VNR/ATRA MLNP were spherical particles with particle size and zeta potential of 158 nm and 12.3 mV. CISP/VNR/ATRA MLNP (81.36%) was uptake by cancer cells in vitro. CISP/VNR/ATRA MLNP could significantly inhibit the in vivo antitumor growth and suspended the tumor volume from 1440 mm3 to 220 mm3. Conclusion: It could be concluded that the CISP/VNR/ATRA MLNP may be used as a promising system for lung cancer combination treatment.

19.
Cancer Lett ; 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33152402

RESUMO

Immunoglobulin-like transcript (ILT) 3 is an immunosuppressive molecule that negatively regulates myeloid cell activation. ILT3 overexpression in tumor cells induces immune escape of solid tumors and facilitates invasion of monocytic acute myelocytic leukemia cells. However, the expression and function of ILT3 in non-small cell lung cancer (NSCLC) cells remain elusive. Herein, we found that ILT3 was enriched in human NSCLC cells, and predicted advanced disease and poor overall survival. ILT3 overexpression enhanced the migration and invasion of NSCLC cells and tubule formation of human umbilical vein endothelial cells by upregulating and interacting with its ligand apolipoprotein E (ApoE) in vitro. Mechanistically, ILT3 recruited SHP2 and SHIP1, and subsequently activated ERK1/2 signaling mediating epithelial-mesenchymal transition (EMT) and increasing vascular endothelial growth factor (VEGF)-A expression in NSCLC cells, which are responsible for tumor cell motility and angiogenesis, respectively. Using murine metastasis models, we further confirmed ILT3 promoted NSCLC metastasis and explored the exact correlation of ILT3 with ApoE, EMT, and VEGF-A in vivo. These results unraveled novel mechanisms for ILT3-induced tumor progression and proposed ILT3 as a potential therapeutic target and prognostic biomarker for NSCLC patients.

20.
Artigo em Inglês | MEDLINE | ID: mdl-33191910

RESUMO

BACKGROUND: 5-fluorouracil (5-FU) is a cytotoxic antimetabolite that interferes with nucleic acid metabolism in both normal and cancer cells. Capecitabine is a prodrug of 5-FU, and S-1 is an oral 5-FU derivative. Patients usually tolerate treatment with one fluorouracil drug well. However, simultaneous application of two or more fluorouracil drugs such as capecitabine and S-1 can lead to life-threatening toxicities. CASE REPORT: A 73-year-old male with gastric and rectal cancer was admitted to the emergency department because of severe oral mucositis, hand-foot syndrome, and fever after concurrently taking capecitabine (1.5 g twice a day) and S-1 (50 mg twice a day) for 3 days at home. He was immediately given recombinant human granulocyte colony-stimulating factor (200 mg SC once a day) and recombinant human thrombopoietin (15,000 IU SC once a day). Hemagglutinin (1 unit IM once a day) was administered. Anti-infection and mucosal care were started promptly. A few days later, he developed supraventricular premature beats and short flutter requiring cardioversion. After comprehensive treatment, the patient's infection was effectively controlled, and mucosal damage and cardiac toxicity were significantly alleviated. CONCLUSION: 5-FU overdose caused by the combination of capecitabine and S-1 can cause serious adverse reactions. Careful checking of the medical orders and extensive education of patients to recognize the symptoms of toxicity may reduce the occurrence of such adverse reactions.

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