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1.
Clin Cancer Res ; 2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-33947693

RESUMO

PURPOSE: Intratumoral hepatitis B virus (HBV) integrations and mutations are related to hepatocellular carcinoma (HCC) progression. Circulating cell-free DNA (cfDNA) has shown itself as a powerful non-invasive biomarker for cancer. However, the HBV integration and mutation landscape on cfDNA remains unclear. EXPERIMENTAL DESIGN: A cSMART (Circulating Single-Molecule Amplification and Resequencing Technology)-based method (SIM) was developed to simultaneously investigate HBV integration and mutation landscapes on cfDNA with HBV-specific primers covering the whole HBV genome. 481 HCC and 517 liver cirrhosis (LC) patients were recruited in the study. RESULTS: A total of 6,861 integration breakpoints including TERT and KMT2B were discovered in HCC cfDNA, more than in LC. The concentration of circulating tumor DNA (ctDNA) was positively correlated with the detection rate of these integration hotspots and total HBV integration events in cfDNA. To track the origin of HBV integrations in cfDNA, whole-genome sequencing (WGS) was performed on their paired tumor tissues. The paired comparison of WGS data from tumor tissues and SIM data from cfDNA confirmed most recurrent integration events in cfDNA originated from tumor tissue. The mutational landscape across the whole HBV genome was firstly generated for both HBV genotype C and B. A region from nt1100 to nt1500 containing multiple HCC risk mutation sites (OR>1) was identified as a potential HCC-related mutational hot-zone. CONCLUSIONS: Our study provides an in-depth delineation of HBV integration/mutation landscapes at cfDNA level and did a comparative analysis with their paired tissues. These findings shed light on the possibilities of non-invasive detection of virus insertion/mutation.

2.
Medicine (Baltimore) ; 100(18): e25556, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33950929

RESUMO

BACKGROUND: Rheumatoid arthritis is a kind of chronic crippling disease, the condition is complex, the course of the disease is repeated, seriously affecting the quality of life of patients. Adverse reactions and drug resistance associated with conventional treatment can no longer meet the clinical need. Therefore, complementary and alternative therapies need to be explored. The evidence shows that silver needle therapy has advantages in the treatment of rheumatoid arthritis, but there is a lack of standard clinical studies to verify this conclusion. METHODS: This is a prospective randomized controlled trial to study the efficacy and safety of silver needles in the treatment of rheumatoid arthritis. Approved by the Clinical Research Ethics Committee of our hospital. The patients are randomly divided into a treatment group (silver needle treatment group) or control group (routine western medicine treatment group). The patients are followed up for 2 months after 4 weeks of treatment. Observation indicators include: TCM symptom score, HAQDI score, DAS-28 score, laboratory indicators, adverse reactions and so on. Data will be analyzed using the statistical software package SPSS version 18.0 (Chicago, IL). DISCUSSION: This study will evaluate the clinical efficacy of a silver needle in the treatment of rheumatoid arthritis. The results of this study will provide a reliable reference for the clinical use of a silver needle in the treatment of rheumatoid arthritis. TRIAL REGISTRATION: OSF Registration number: DOI 10.17605/OSF.IO/4X5QB.

3.
Inorg Chem ; 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33847494

RESUMO

Herein, we reported a facile strategy for the preparation of trifunctional ionic metal-organic frameworks (MOFs) incorporating imidazolium cation functionalities. This strategy exploits the Debus-Radziszewski reaction to create the cationic imidazole ring by postsynthetic modification, meanwhile introducing exchangeable counteranions. On the basis of this strategy, MIL-101-IMOH-Br- has been synthesized, which combines Lewis acidic sites, Brønsted acidic sites, and nucleophilic centers to achieve catalysis for the carbon dioxide-epoxide cycloaddition into cyclocarbonate without any cocatalyst and solvent.

4.
Global Spine J ; : 21925682211005732, 2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33896211

RESUMO

STUDY DESIGN: Retrospective pooled analysis of individual patient data. OBJECTIVES: Spinal chondroblastoma (CB) is a very rare pathology and its clinicopathological and prognostic features remain unclear. Here, we sought to characterize the clinicopathological data of a large spinal CB cohort and determine factors affecting the local recurrence-free survival (LRFS) and overall survival (OS) of patients. METHODS: Electronic searches using Medline, Embase, Google Scholar and Wanfang databases were performed to identify eligible studies per predefined criteria. A retrospective review was also conducted to include additional patients at our center. RESULTS: Twenty-seven studies from the literature and 8 patients from our local institute were identified, yielding a total of 61 patients for analysis. Overall, there were no differences in clinicopathological characteristics between the local and literature cohorts, except for absence or presence of spinal canal invasion by tumor on imagings and chicken-wire calcification in tumor tissues. Univariate Kaplan-Meier analysis revealed that previous treatment, preoperative or postoperative neurological deficits, type of tumor resection, secondary aneurysmal bone cyst (ABC), chicken-wire calcification and radiotherapy correlated closely with LRFS, though only type of tumor resection, chicken-wire calcification and radiotherapy were predictive of outcome based on multivariate Cox analysis. Analyzing OS, we found that a history of preoperative treatment, concurrent ABC, chicken-wire calcification, type of tumor resection and adjuvant radiotherapy had a significant association with survival, whereas only type of tumor resection remained statistically significant after adjusting for other covariables. CONCLUSION: These data may be helpful in prognostic risk stratification and individualized therapy decision making for patients.

5.
ACS Chem Neurosci ; 12(7): 1162-1169, 2021 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-33710861

RESUMO

Alzheimer's disease (AD) is a neurodegenerative disease with high morbidity. The deposition of oligomerized amyloid ß (Aß) is the pathological feature of AD. The Aß-caused neuronal oxidative stress and cellular senescence play an important role in the development and progression of AD. Olmesartan is a novel angiotensin receptor blocker with promising antihypertensive properties and has recently been reported to exert anti-inflammatory and antioxidative stress effects. Blood pressure control using Angiotensin receptor blockers has shown multiple benefits in Alzheimer's disease models. In the present study, the effect of Olmesartan on oligomerized amyloid ß (Aß)-induced cellular senescence was investigated in cultured M17 neuronal cells. Our results show that Olmesartan treatment significantly ameliorates oligomerized Aß-elevated ROS and MDA levels, as well as the induced senescent cells number. At the molecular level, Olmesartan inhibits the elevated expression of senescence biomarkers (p16 and p21). Furthermore, Olmesartan potently reversed the increased K382 acetylation of p53 and the downregulation of SIRT1. Moreover, we show that the effect of Olmesartan against cell senescence and deacetylation of p53 was abolished by inhibition of SIRT1, either by using nicotinamide or by transfection with SIRT1 siRNA. In conclusion, Olmesartan prevents oligomerized Aß-induced cellular senescence in neuronal cells by downregulating p16 and p21 through a SIRT1 dependent deacetylation of p53; our finding indicates that Olmesartan has a protective effect in Aß-induced neurotoxicity.

6.
mBio ; 12(2)2021 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-33727348

RESUMO

Monoclonal antibody (MAb) 2C7 recognizes a lipooligosaccharide epitope expressed by most clinical Neisseria gonorrhoeae isolates and mediates complement-dependent bactericidal activity. We recently showed that a recombinant human IgG1 chimeric variant of MAb 2C7 containing an E430G Fc modification (2C7_E430G), which enhances complement activation, outperformed the parental MAb 2C7 (2C7_WT) in vivo Because natural infection with N. gonorrhoeae often does not elicit protective immunity and reinfections are common, approaches that prolong bacterial control in vivo are of great interest. Advances in DNA-based approaches have demonstrated the combined benefit of genetic engineering, formulation optimizations, and facilitated delivery via CELLECTRA-EP technology, which can induce robust in vivo expression of protective DNA-encoded monoclonal antibodies (DMAbs) with durable serum activity relative to traditional recombinant MAb therapies. Here, we created optimized 2C7-derived DMAbs encoding the parental Fc (2C7_WT) or complement-enhancing Fc variants (2C7_E430G and 2C7_E345K). 2C7 DMAbs were rapidly generated and detected throughout the 4-month study. While all complement-engaging 2C7 variants facilitated rapid clearance following primary N. gonorrhoeae challenge (day 8 after DMAb administration), the complement-enhancing 2C7_E430G variant demonstrated significantly higher potency against mice rechallenged 65 days after DMAb administration. Passive intravenous transfer of in vivo-produced, purified 2C7 DMAbs confirmed the increased potency of the complement-enhancing variants. This study highlights the ability of the DMAb platform to launch the in vivo production of antibodies engineered to promote and optimize downstream innate effector mechanisms such as complement-mediated killing, leading to hastened bacterial elimination.IMPORTANCE Neisseria gonorrhoeae has become resistant to most antibiotics in clinical use. Currently, there is no safe and effective vaccine against gonorrhea. Measures to prevent the spread of gonorrhea are a global health priority. A monoclonal antibody (MAb) called 2C7, directed against a lipooligosaccharide glycan epitope expressed by most clinical isolates, displays complement-dependent bactericidal activity and hastens clearance of gonococcal vaginal colonization in mice. Fc mutations in a human IgG1 chimeric version of MAb 2C7 further enhance complement activation, and the resulting MAb displays greater activity than wild-type MAb 2C7 in vivo Here, we utilized a DNA-encoded MAb (DMAb) construct designed to launch production and assembly of "complement-enhanced" chimeric MAb 2C7 in vivo The ensuing rapid and sustained MAb 2C7 expression attenuated gonococcal colonization in mice at 8 days as well as 65 days postadministration. The DMAb system may provide an effective, economical platform to deliver MAbs for durable protection against gonorrhea.

7.
ACS Synth Biol ; 10(4): 749-755, 2021 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-33784075

RESUMO

Herein, we constructed a new type of hydrogel based artificial cells supporting long-lived protein synthesis, post-translational modification, and gene networks. We constructed the artificial cells by immobilizing the transcription and translation system from E. coli cytoplasmic extract onto the polyacrylamide hydrogel. With the continuous supply of energy and nutrition, the artificial cells were capable of stable protein expression for at least 30 days. Functional proteins which were difficult to produce in vivo, including colicin E1 and urokinase, were synthesized in the artificial cells with high bioactivity. Furthermore, we constructed a sigma factor based genetic oscillator in the artificial cells. The artificial cells not only provide a powerful platform for continuous protein synthesis and convenient design and testing of genetic networks, but also hold great promise for the development of metabolic engineering, drug delivery, and biosensors.

8.
Zhongguo Zhong Yao Za Zhi ; 46(1): 52-56, 2021 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-33645051

RESUMO

ATP-binding cassette(ABC) transporters are one of the largest protein families in organisms, with important effects in regulating plant growth and development, root morphology, transportation of secondary metabolites and resistance of stress. Environmental stress promotes the biosynthesis and accumulation of secondary metabolites, which determines the quality of medicinal plants. Therefore, how to improve the accumulation of secondary metabolites has been a hotspot in studying medicinal plants. Many studies have showed that ABC transporters are extremely related to the transportation and accumulation of secondary metabolites in plants. Recently, with the great development of genomics and transcriptomic sequencing technology, the regulatory mechanisms of ABC transporters on secondary metabolites have attached great attentions in medicinal plants. This paper reviewed the mechanisms of different groups of ABC transporters in transporting secondary metabolites through cell membranes. This paper provided key theoretical basis and technical supports in studying the mechanisms of ABC transporters in medicinal plant, and promoting the accumulation of secondary metabolites, in order to improve the quality of medicinal plants.


Assuntos
Transportadores de Cassetes de Ligação de ATP , Plantas Medicinais , Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , Transporte Biológico , Desenvolvimento Vegetal , Plantas Medicinais/genética , Plantas Medicinais/metabolismo , Estresse Fisiológico
9.
Proc Natl Acad Sci U S A ; 118(10)2021 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-33649215

RESUMO

Surface ozone is a severe air pollution problem in the North China Plain, which is home to 300 million people. Ozone concentrations are highest in summer, driven by fast photochemical production of hydrogen oxide radicals (HOx) that can overcome the radical titration caused by high emissions of nitrogen oxides (NOx) from fuel combustion. Ozone has been very low during winter haze (particulate) pollution episodes. However, the abrupt decrease of NOx emissions following the COVID-19 lockdown in January 2020 reveals a switch to fast ozone production during winter haze episodes with maximum daily 8-h average (MDA8) ozone concentrations of 60 to 70 parts per billion. We reproduce this switch with the GEOS-Chem model, where the fast production of ozone is driven by HOx radicals from photolysis of formaldehyde, overcoming radical titration from the decreased NOx emissions. Formaldehyde is produced by oxidation of reactive volatile organic compounds (VOCs), which have very high emissions in the North China Plain. This remarkable switch to an ozone-producing regime in January-February following the lockdown illustrates a more general tendency from 2013 to 2019 of increasing winter-spring ozone in the North China Plain and increasing association of high ozone with winter haze events, as pollution control efforts have targeted NOx emissions (30% decrease) while VOC emissions have remained constant. Decreasing VOC emissions would avoid further spreading of severe ozone pollution events into the winter-spring season.


Assuntos
Poluição do Ar/análise , Ozônio/análise , Material Particulado/análise , Estações do Ano , Compostos Orgânicos Voláteis , China , Produtos Agrícolas , Monitoramento Ambiental , Poluição Ambiental , Humanos , Óxidos de Nitrogênio/química , Pandemias , Saúde Pública
10.
CJEM ; 2021 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-33715143

RESUMO

BACKGROUND: Recent studies have presented concerning data on the safety of cardioversion for acute atrial fibrillation and flutter. We conducted this meta-analysis to evaluate the effect of oral anticoagulation use on thromboembolic events post-cardioversion of low-risk acute atrial fibrillation and flutter patients of < 48 h in duration. METHODS: We searched MEDLINE, Embase, and Cochrane from inception through February 6, 2020 for studies reporting thromboembolic events post-cardioversion of acute atrial fibrillation and flutter. Main outcome was thromboembolic events within 30 days post-cardioversion. Primary analysis compared thromboembolic events based on oral anticoagulation use versus no oral anticoagulation use. Secondary analysis was based on baseline thromboembolic risk. We performed meta-analyses where 2 or more studies were available, by applying the DerSimonian-Laird random-effects model. Risk of bias was assessed with the Quality in Prognostic Studies tool. RESULTS: Of 717 titles screened, 20 studies met inclusion criteria. Primary analysis of seven studies with low risk of bias demonstrated insufficient evidence regarding the risk of thromboembolic events associated with oral anticoagulation use (RR = 0.82 where RR < 1 suggests decreased risk with oral anticoagulation use; 95% CI 0.27 to 2.47; I2 = 0%). Secondary analysis of 13 studies revealed increased risk of thromboembolic events with high baseline thromboembolic risk (RR = 2.25 where RR > 1 indicates increased risk with higher CHADS2 or CHA2DS2-VASc scores; 95% CI 1.25 to 4.04; I2 = 0%). CONCLUSION: Primary analysis revealed insufficient evidence regarding the effect of oral anticoagulation use on thromboembolic events post-cardioversion of low-risk acute atrial fibrillation and flutter, though the event rate is low in contemporary practice. Our findings can better inform patient-centered decision-making when considering 4-week oral anticoagulation use for acute atrial fibrillation and flutter patients.

11.
Ying Yong Sheng Tai Xue Bao ; 32(3): 931-941, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33754559

RESUMO

To clarify the effects of combined applications of chlorocholine chloride (CCC) and nitrogen fertilizer (CN) on nitrogen metabolism and nitrogen use efficiency of summer maize, we conducted a field experiment in Xinxiang experimental station of Chinese Academy of Agricultural Sciences in 2018 and 2019, with four nitrogen application rates (0, 62.5, 125 and 187.5 kg·hm-2), and two maize varieties of Jingnongke 728 (JNK728) and Zhongdan 909 (ZD909). The results showed that across the two years CN-CCC increased maize yield by 7.7% and 5.0% under the nitrogen application rates of 62.5 kg·hm-2 and 125 kg·hm-2, respectively. CN-CCC increased the contents of nitrate reductase, glutamine synthetase, glutamate synthetase and soluble protein, and finally promoted nitrogen metabolism. Under the low and middle nitrogen application conditions (62.5 kg·hm-2 and 125 kg·hm-2), plant nitrogen content of JNK728 and ZD909 increased by 17.6% and 30.3%, grain nitrogen content increased by 10.3% and 17.4%, nitrogen partial productivity, agronomic efficiency of applied nitrogen, recovery efficiency of applied nitrogen, nitrogen use efficiency increased by 10.0%, 15.7%, 23.3%, 24.8% and 5.7%, 15.0%, 49.9%, 71.7%, respectively. In conclusion, appropriate basic application of CN-CCC could enhance nitrogen metabolism, increase nitrogen use efficiency and grain yield of summer maize. Our results showed that CCC combined basic nitrogen application of 125 kg·hm-2 had the best effect.


Assuntos
Fertilizantes , Nitrogênio , Agricultura , China , Clormequat , Nitrogênio/análise , Solo , Zea mays
12.
Plant Cell Environ ; 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33675080

RESUMO

For perennials in boreal and temperate ecosystems, bud dormancy is crucial for survival in harsh winter. Dormancy is released by prolonged exposure to low temperatures and is followed by reactive growth in the spring. Lysine acetylation (Kac) is one of the major post-translational modifications (PTMs) that are involved in plant response to environmental signals. However, little information is available on the effects of Kac modification on bud dormancy release. Here, we report the dynamics of lysine acetylome in hybrid poplar (Populus tremula × Populus alba) dormant buds. A total of 7,594 acetyl-sites from 3,281 acetyl-proteins were identified, representing a large dataset of lysine acetylome in plants. Of them, 229 proteins were differentially acetylated during bud dormancy release and were mainly involved in the primary metabolic pathways. Site-directed mutagenesis enzymatic assays showed that Kac strongly modified the activities of two key enzymes of primary metabolism, pyruvate dehydrogenase (PDH) and isocitrate dehydrogenase (IDH). We thus propose that Kac of enzymes could be an important strategy for reconfiguration of metabolic processes during bud dormancy release. In all, our results reveal the importance of Kac in bud dormancy release and provide a new perspective to understand the molecular mechanisms of seasonal growth of trees.

13.
Biochem Biophys Res Commun ; 550: 127-133, 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33689881

RESUMO

Meiotic homologous recombination (HR) initiates with the programmed generation of DNA double-strand breaks (DSBs), which result in the exchange of genetic information and genome diversity. This process requires the tight cooperation of the MRE11-RAD50-NBS1 (MRN) complex to promote DSB formation and DNA end resection. However, the mechanism regulating MRN complex remains to be explored. In the present study, we report that MRN-interacting protein, MRNIP, is a novel factor for HR and is crucial for the expression of the MRN complex and loading of recombinases DMC1/RAD51. Knockout of Mrnip in mice led to aberrant synapsis, impaired HR, and male subfertility. In conclusion, MRNIP is a novel HR factor that probably promotes meiotic progression through the MRN complex.

15.
Huan Jing Ke Xue ; 42(4): 1591-1599, 2021 Apr 08.
Artigo em Chinês | MEDLINE | ID: mdl-33742794

RESUMO

Based on the air pollution emission inventory technical methodology, this study conducted a quantitative analysis on the changes in major air pollutant emissions in Beijing-Tianjin-Hebei and its surrounding areas from the 'New Year Haze' in the autumn and winter of 2016-2017 to the 'Pandemic Haze' in the autumn and winter of 2019-2020. The contributions of the implementation of air pollution prevention and control policies and the COVID-19 pandemic to major air pollutant emission reductions were studied, and their impacts on the regional air quality under adverse meteorological conditions were simulated using an air quality model. The results showed that from the 'New Year Haze' in Dec 2016-Jan 2017 to the 'Pandemic Haze' in Jan-Feb 2020, the major air pollutant emissions in the region had dropped by approximately 50%, and the average concentration of PM2.5 was potentially reduced by more than 40% under adverse meteorological conditions. The most effective emission reduction measures included the clean heating project and raising the standards in key industrial sectors, such as the iron and steel industry, coal-fired boilers, and power plants, which contributed 67.1% and 53.4% of the emission reductions in SO2 and PM2.5, respectively. The COVID-19 pandemic predominantly affected the mobile sources and light industry, which contributed 71.9% and 68.2% of the emission reductions in NOx and VOCs, respectively. The implementation of air pollution prevention and control policies contributed substantially to the improvement of regional air quality, which effectively reduced the intensity and extent of the heavy pollution process under unfavorable meteorological conditions. The regional average PM2.5 concentration was reduced by 26%, and the number of days experiencing heavy pollution decreased by 44%. Due to the impacts of the COVID-19 pandemic, the average PM2.5 concentration in the region was reduced by an additional 24%, and the duration and extent of heavy pollution decreased even further.

17.
J Med Chem ; 64(4): 2125-2138, 2021 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-33559473

RESUMO

A series of fluorescent ligands, which were systematically constructed from thiazole orange scaffold, was investigated for their interactions with G-quadruplex structures and antitumor activity. Among the ligands, compound 3 was identified to exhibit excellent specificity toward telomere G4-DNA over other nucleic acids. The affinity of 3-Htg24 was almost 5 times higher than that of double-stranded DNA and promoter G4-DNA. Interaction studies showed that 3 may bind to both G-tetrad and the lateral loop near the 5'-end. The intracellular colocalization with BG4 and competition studies with BRACO19 reveal that 3 may interact with G4-structures. Moreover, 3 reduces the telomere length and downregulates hTERC and hTERT mRNA expression in HeLa cells. The cytotoxicity of 3 against cancer cells (IC50 = 12.7-16.2 µM) was found to be generally higher than noncancer cells (IC50 = 52.3 µM). The findings may support that the ligand is telomere G4-DNA specific and may provide meaningful insights for anticancer drug design.


Assuntos
Benzotiazóis/farmacologia , DNA/metabolismo , Regulação para Baixo/efeitos dos fármacos , Corantes Fluorescentes/farmacologia , Quadruplex G , Quinolinas/farmacologia , Estirenos/farmacologia , Benzotiazóis/síntese química , Benzotiazóis/metabolismo , Linhagem Celular Tumoral , DNA/genética , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/metabolismo , Humanos , Ligantes , Microscopia Confocal , Microscopia de Fluorescência , Quinolinas/síntese química , Quinolinas/metabolismo , RNA/metabolismo , Estirenos/síntese química , Estirenos/metabolismo , Telomerase/metabolismo
19.
Acta Pharmacol Sin ; 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33608672

RESUMO

RAS-driven colorectal cancer relies on glucose metabolism to support uncontrolled growth. However, monotherapy with glycolysis inhibitors like 2-deoxy-D-glucose causes limited effectiveness. Recent studies suggest that anti-tumor effects of glycolysis inhibition could be improved by combination treatment with inhibitors of oxidative phosphorylation. In this study we investigated the effect of a combination of 2-deoxy-D-glucose with lovastatin (a known inhibitor of mevalonate pathway and oxidative phosphorylation) on growth of KRAS-mutant human colorectal cancer cell lines HCT116 and LoVo. A combination of lovastatin (>3.75 µM) and 2-deoxy-D-glucose (>1.25 mM) synergistically reduced cell viability, arrested cells in the G2/M phase, and induced apoptosis. The combined treatment also reduced cellular oxygen consumption and extracellular acidification rate, resulting in decreased production of ATP and lower steady-state ATP levels. Energy depletion markedly activated AMPK, inhibited mTOR and RAS signaling pathways, eventually inducing autophagy, the cellular pro-survival process under metabolic stress, whereas inhibition of autophagy by chloroquine (6.25 µM) enhanced the cytotoxic effect of the combination of lovastatin and 2-deoxy-D-glucose. These in vitro experiment results were reproduced in a nude mouse xenograft model of HCT116 cells. Our findings suggest that concurrently targeting glycolysis, oxidative phosphorylation, and autophagy may be a promising regimen for the management of RAS-driven colorectal cancers.

20.
Nanotheranostics ; 5(2): 240-255, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33614400

RESUMO

White blood cells (WBCs) are a key component of the mammalian immune system and play an essential role in surveillance, defense, and adaptation against foreign pathogens. Apart from their roles in the active combat of infection and the development of adaptive immunity, immune cells are also involved in tumor development and metastasis. Antibody-based therapeutics have been developed to regulate (i.e. selectively activate or inhibit immune function) and harness immune cells to fight malignancy. Alternatively, non-invasive tracking of WBC distribution can diagnose inflammation, infection, fevers of unknown origin (FUOs), and cancer. Magnetic Particle Imaging (MPI) is a non-invasive, non-radioactive, and sensitive medical imaging technique that uses safe superparamagnetic iron oxide nanoparticles (SPIOs) as tracers. MPI has previously been shown to track therapeutic stem cells for over 87 days with a ~200 cell detection limit. In the current work, we utilized antibody-conjugated SPIOs specific to neutrophils for in situ labeling, and non-invasive and radiation-free tracking of these inflammatory cells to sites of infection and inflammation in an in vivo murine model of lipopolysaccharide-induced myositis. MPI showed sensitive detection of inflammation with a contrast-to-noise ratio of ~8-13.

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