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1.
Drug Resist Updat ; 72: 101013, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38041877

RESUMO

Radioiodine-refractory differentiated thyroid cancer (RAIR-DTC) is difficult to treat with radioactive iodine because of the absence of the sodium iodide transporter in the basement membrane of thyroid follicular cells for iodine uptake. This is usually due to the mutation or rearrangement of genes and the aberrant activation of signal pathways, which result in abnormal expression of thyroid-specific genes, leading to resistance of differentiated thyroid cancer cells to radioiodine therapy. Therefore, inhibiting the proliferation and growth of RAIR-DTC with multikinase inhibitors and other drugs or restoring its differentiation and then carrying out radioiodine therapy have become the first-line treatment strategies and main research directions. The drugs that regulate these kinases or signaling pathways have been studied in clinical and preclinical settings. In this review, we summarized the major gene mutations, gene rearrangements and abnormal activation of signaling pathways that led to radioiodine resistance of RAIR-DTC, as well as the medicine that have been tested in clinical and preclinical trials.


Assuntos
Neoplasias da Glândula Tireoide , Humanos , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/radioterapia , Radioisótopos do Iodo/uso terapêutico , Transdução de Sinais
2.
J Neurochem ; 163(3): 220-232, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35862478

RESUMO

BDNF and its expressing neurons in the brain critically control feeding and energy expenditure (EE) in both rodents and humans. However, whether BDNF neurons would function in thermoregulation during temperature challenges is unclear. Here, we show that BDNF neurons in the dorsomedial hypothalamus (DMHBDNF ) of mice are activated by afferent cooling signals. These cooling-activated BDNF neurons are mainly GABAergic. Activation of DMHBDNF neurons or the GABAergic subpopulations is sufficient to increase body temperature, EE, and physical activity. Conversely, blocking DMHBDNF neurons substantially impairs cold defense and reduces energy expenditure, physical activity, and UCP1 expression in BAT, which eventually results in bodyweight gain and glucose/insulin intolerance. Therefore, we identify a subset of DMHBDNF neurons as a novel type of cooling-activated neurons to promote cold defense. Thus, we reveal a critical role of BDNF circuitry in thermoregulation, which deepens our understanding of BDNF in controlling energy homeostasis and obesity.


Assuntos
Fator Neurotrófico Derivado do Encéfalo , Temperatura Baixa , Hipotálamo , Animais , Humanos , Camundongos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Metabolismo Energético , Hipotálamo/metabolismo , Neurônios/metabolismo
3.
Pharm Biol ; 60(1): 1349-1364, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35868020

RESUMO

CONTEXT: The extracts of Aspongopus chinensis Dallas (Pentatomidae), an insect used in traditional Chinese medicine, have a complex chemical composition and possess multiple pharmacological activities. OBJECTIVE: This study comprehensively characterizes the chemical constituents of A. chinensis by an integrated targeted and untargeted strategy using UPLC-QTOF-MS combined with molecular networking. MATERIALS AND METHODS: The ultra-performance liquid chromatography-tandem quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) combined with molecular networking-based dereplication was proposed to facilitate the identification of the chemical constituents of aqueous and ethanol extracts of A. chinensis. The overall strategy was designed to avoid the inefficiency and costliness of traditional techniques. The targeted compounds discovered in the A. chinensis extracts were identified by searching a self-built database, including fragment ions, precursor ion mass, and other structural information. The untargeted compounds were identified by analyzing the relationship between different categories, fragmentation pathways, mass spectrometry data, and the structure of the same cluster of nodes within the molecular network. The untargeted strategy was verified using commercial standard samples under the same mass spectrometry conditions. RESULTS: The proposed integrated targeted and untargeted strategy was successfully applied to the comprehensive profiling of the chemical constituents of aqueous and ethanol extracts of A. chinensis. A total of 124 compounds such as fatty acids, nucleosides, amino acids, and peptides, including 74 compounds that were reported for the first time, were identified in this study. CONCLUSIONS: The integrated strategy using LC tandem HRMS combined with molecular networking could be popularised for the comprehensive profiling of chemical constituents of other traditional insect medicines.


Assuntos
Medicamentos de Ervas Chinesas , Espectrometria de Massas em Tandem , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/química , Etanol , Medicina Tradicional Chinesa , Espectrometria de Massas em Tandem/métodos
4.
AJR Am J Roentgenol ; 216(4): 894-902, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33566635

RESUMO

OBJECTIVE. One central question pertaining to mammography quality relates to discerning the optimal recall rate to maximize cancer detection while minimizing unnecessary downstream diagnostic imaging and breast biopsies. We examined the trade-offs for higher recall rates in terms of biopsy recommendations and cancer detection in a single large health care organization. MATERIALS AND METHODS. We included 2D analog, 2D digital, and 3D digital (tomosynthesis) screening mammography examinations among women 40-79 years old performed between January 1, 2005, and December 31, 2017, with cancer follow-up through 2018. There were 36, 67, and 38 radiologists who read at least 1000 2D analog examinations, 2D digital examinations, and 3D tomosynthesis examinations, respectively, who were included in these analyses. Using logistic regression with marginal standardization, we estimated radiologist-specific mean recall (abnormal interpretations/1000 mammograms), biopsy recommendation, cancer detection (screening-detected in situ and invasive cancers/1000 mammograms), and minimally invasive cancer detection rates while adjusting for differences in patient characteristics. RESULTS. Among 1,060,655 screening mammograms, the mean recall rate was 10.7%, the cancer detection rate was 4.0/1000 mammograms, and the biopsy recommendation rate was 1.60%. Recall rates between 7% and 9% appeared to maximize cancer detection while minimizing unnecessary biopsies. CONCLUSION. The results of this investigation are in contrast to those of a recent study suggesting appropriateness of higher recall rates. The "sweet spot" for optimal cancer detection appears to be in the recall rate range of 7-9% for both 2D digital mammography and 3D tomosynthesis. Too many women are being called back for diagnostic imaging, and new benchmarks could be set to reduce this burden.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Mamografia , Adulto , Idoso , Neoplasias da Mama/diagnóstico , Chicago , Feminino , Humanos , Mamografia/métodos , Mamografia/estatística & dados numéricos , Pessoa de Meia-Idade , Sistema de Registros/estatística & dados numéricos , Estudos Retrospectivos
5.
Mol Breed ; 41(7): 43, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37309387

RESUMO

Improving yield is one of the most important targets of sesame breeding. Identifying quantitative trait loci (QTLs) of yield-related traits is a prerequisite for marker-assisted selection (MAS) and QTL/gene cloning. In this study, a BC1 population was developed and genotyped with the specific-locus amplified fragment (SLAF) sequencing technology, and a high-density genetic map was constructed. The map consisted of 13 linkage groups, contained 3528 SLAF markers, and covered a total of 1312.52 cM genetic distance, with an average distance of 0.37 cM between adjacent markers. Based on the map, 46 significant QTLs were identified for seven yield-related traits across three environments. These QTLs distributed on 11 linkage groups, each explaining 2.34-71.41% of the phenotypic variation. Of the QTLs, 23 were stable QTLs that were detected in more than one environment, and 20 were major QTLs that explained more than 10% of the corresponding phenotypic variation in at least one environment. Favorable alleles of 38 QTLs originated from the locally adapted variety, Yuzhi 4; the exotic germplasm line, BS, contributed favorable alleles to only 8 QTLs. The results should provide useful information for future molecular breeding and functional gene cloning. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-021-01236-x.

6.
J Environ Sci (China) ; 106: 83-96, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34210442

RESUMO

In this work, we employed waste activated sludge (WAS) as carbon source to prepare ultrahigh specific surface area (SSA) biopolymers-based carbons (BBCs) through alkali (KOH) treatment coupled to pyrolysis strategy. Before the pyrolysis process, the involvement of KOH made a great recovery of soluble biopolymers from WAS, resulting in highly-efficient catalytic pyrolysis. The Brunner-Emmett-Teller and pore volume of BBCs prepared at 800°C (BBC800) reached the maximum at 2633.89 m2·g-1 and 2.919 m3·g-1, respectively. X-ray photoelectron spectroscopy suggested that aromatic carbon in the form of C=C was the dominant fraction of C element in BBCs. The N element in BBCs were composed of pyrrolic nitrogen and pyridinic nitrogen at 700°C, while a new graphitic nitrogen appeared over 800°C. As a refractory pollutant of wastewater treatment plants, tetracycline (TC) was selected to evaluate adsorption performance of BBCs. The adsorption behavior of BBCs towards TC was conformed to the pseudo-second-order kinetic and the Langmuir models, signifying that chemisorption of monolayers was dominant in TC adsorption. The adsorption capacity of BBC800 reached the maximum at 877.19 mg·g-1 for 90 min at 298 K. Thermodynamic analysis indicated that the adsorption process was endothermic and spontaneous. Hydrogen bonding and π-π stacking interaction were mainly responsible for TC adsorption, and interfacial diffusion was the main rate-control step in adsorption process. The presence of soluble microbial products (SMPs) enhanced TC removal. This work provided a novel strategy to prepare bio-carbon with ultrahigh SSA using WAS for highly-efficient removal of organic pollutants.


Assuntos
Esgotos , Poluentes Químicos da Água , Adsorção , Álcalis , Biopolímeros , Carbono , Carvão Vegetal , Cinética , Pirólise , Poluentes Químicos da Água/análise
7.
J Cell Mol Med ; 24(11): 6324-6339, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32396269

RESUMO

Lung cancer has the highest mortality rate among human cancers, and the majority of deaths can be attributed to metastatic spread. Lung cancer stem cells (CSCs) are a component of the tumour microenvironment that contributes to this process. Exosomes are small membrane vesicles secreted by all types of cells that mediate cell interactions, including cancer metastasis. Here, we show that lung CSC-derived exosomes promote the migration and invasion of lung cancer cells, up-regulate expression levels of N-cadherin, vimentin, MMP-9 and MMP-1, and down-regulate E-cadherin expression. Moreover, we verified that these exosomes contribute to a pro-metastatic phenotype in lung cancer cells via miR-210-3p transfer. The results of bioinformatics analysis and dual-luciferase reporter assays further indicated that miR-210-3p may bind to fibroblast growth factor receptor-like 1 (FGFRL1); silencing FGFRL1 enhanced the metastatic ability of lung cancer cells, whereas overexpressing FGFRL1 suppressed metastasis. Taken together, our results provide new insights into a potential molecular mechanism whereby lung CSC-derived exosomal miR-210-3p targets FGFRL1 to promote lung cancer metastasis. FGFRL1 may be a promising therapeutic target in lung cancer.


Assuntos
Exossomos/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , MicroRNAs/metabolismo , Células-Tronco Neoplásicas/metabolismo , Receptor Tipo 5 de Fator de Crescimento de Fibroblastos/metabolismo , Sequência de Bases , Linhagem Celular Tumoral , Endocitose , Exossomos/ultraestrutura , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Humanos , MicroRNAs/genética , Fenótipo , Esferoides Celulares/metabolismo , Esferoides Celulares/patologia
8.
Langmuir ; 36(9): 2199-2208, 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32075375

RESUMO

DUT-67(Zr) was obtained by a solvothermal route and applied to photocatalytic selective synthesis of thioanisole under light illuminating. The conversion of thioanisole is up to 95%, and the selectivity of methyl phenyl sulfoxide is 98%. The activity of DUT-67(Zr) is over 10 times higher than that of UiO-66. This great increased activity is attributed to the high percentages of oxygen vacancies on DUT-67(Zr). The ESR result shows there are more oxygen vacancies that can expose high density unsaturated Zr sites on DUT-67(Zr). The in situ FTIR reveals that unsaturated Zr sites on DUT-67(Zr) possess Lewis acidity which facilitate the adsorption of the substrates to form the coordination species, promoting the activation of thioanisole. The absorption edge of DUT-67(Zr) with coordination species red-shifts to 360 nm, which can be presented by DRS. Furthermore, the oxygen molecules can be activated by excited electrons to form •O2-. Finally, a possible photocatalytic process of oxidating thioanisole to methyl phenyl sulfoxide based on the coordination effect between DUT-67(Zr) and thioanisole is proposed at a molecular level.

9.
Sensors (Basel) ; 20(18)2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32942655

RESUMO

Three-dimensional (3D) triangulation based on active binocular vision has increasing amounts of applications in computer vision and robotics. An active binocular vision system with non-fixed cameras needs to calibrate the stereo extrinsic parameters online to perform 3D triangulation. However, the accuracy of stereo extrinsic parameters and disparity have a significant impact on 3D triangulation precision. We propose a novel eye gaze based 3D triangulation method that does not use stereo extrinsic parameters directly in order to reduce the impact. Instead, we drive both cameras to gaze at a 3D spatial point P at the optical center through visual servoing. Subsequently, we can obtain the 3D coordinates of P through the intersection of the two optical axes of both cameras. We have performed experiments to compare with previous disparity based work, named the integrated two-pose calibration (ITPC) method, using our robotic bionic eyes. The experiments show that our method achieves comparable results with ITPC.


Assuntos
Fixação Ocular , Robótica , Visão Binocular , Próteses Visuais , Imageamento Tridimensional
10.
J Environ Sci (China) ; 90: 395-407, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32081335

RESUMO

In this work, we proposed a green and cost-effective method to prepare a graphene-based hyper-cross-linked porous carbon composite (GN/HCPC) by one-pot carbonization of hyper-cross-linked polymer (HCP) and glucose. The composite combined the advantages of graphene (GN) and hyper-cross-linked porous carbon (HCPC), leading to high specific surface area (396.93 m2/g) and large total pore volume (0.413 cm3/g). The resulting GN/HCPC composite was applied as an adsorbent to remove 2,4-dichlorophenol (2,4-DCP) from aqueous solutions. The influence of different solution conditions including pH, ionic strength, contact time, system temperature and concentration of humic acid was determined. The maximum adsorption capacity of GN/HCPC composite (calculated by the Langmuir model) could reach 348.43 mg/g, which represented increases of 43.6% and 13.6% over those of the as-prepared pure GN and HCPC, respectively. The Langmuir model and pseudo-second-order kinetic model were found to fit well with the adsorption process. Thermodynamic experiments suggested that the adsorption proceeded spontaneously and endothermically. In addition, the GN/HCPC composite showed high adsorption performance toward other organic contaminants including tetracycline, bisphenol A and phenol. Measurement of the adsorption capability of GN/HCPC in secondary effluent revealed a slight decrease over that in pure water solution. This study demonstrated that the GN/HCPC composite can be utilized as a practical and efficient adsorbent for the removal of organic contaminants in wastewater.


Assuntos
Clorofenóis/química , Grafite/química , Poluentes Químicos da Água/química , Adsorção , Carbono , Cinética , Porosidade
12.
J Environ Sci (China) ; 78: 215-229, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30665640

RESUMO

A novel polyimide-inlaid amine-rich porous organic block copolymer (PI-b-ARPOP) was prepared via one-step polymerization by using different molar ratios of melamine (MA)/terephthalaldehyde (TA)/pyromellitic dianhydride (PMDA), at molar ratios of 4/3/1, 4/2/2 and 4/1/3. The copolymer contained both aminal groups belonging to ARPOP and imide groups belonging to PI, and the bonding styles of the monomers and growth orientations of the polymeric chains were diversiform, forming an excellent porous structure. Notably, MA/TA/PMDA (4/2/2) had a surface area and pore volume of 487.27 m2/g and 1.169 cm3/g, respectively. The adsorption performance of the materials towards 2,4-dichlorophenol (2,4-DCP) in ultra-pure water was systematically studied. The pH value of 7 was optimal in aqueous solution. Na+ and Cl- ions did not negatively affect the adsorption process, while humic acid (HA) slightly decreased the capacity. The equilibrium time was 40 sec, and the maximum adsorption capacity reached 282.49 mg/g at 298 K. The removal process was endothermic and spontaneous, and the copolymer could maintain its porous structure and consistent performance after regeneration by treatment with alkali. Moreover, to further assess the practical applicability of the material, the adsorption performance towards 2,4-DCP in river water was also investigated. This paper demonstrated that the PI-b-ARPOP can be an efficient and practical adsorbent to remove chlorophenols from aqueous solution.


Assuntos
Clorofenóis/química , Polímeros/química , Poluentes Químicos da Água/química , Purificação da Água/métodos , Adsorção , Clorofenóis/análise , Cinética , Porosidade , Poluentes Químicos da Água/análise
13.
Pak J Pharm Sci ; 32(5(Special)): 2419-2422, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31894027

RESUMO

To observe and analyze the clinical effect of nifedipine controlled-release tablets combined with valsartan in the treatment of essential hypertension, and to analyze the adverse reactions of patients. A total of 180 patients with primary hypertension treated in our hospital were enrolled as research objects in the study. According to different treatment regimens, they were divided into the control group treated with valsartan dispersible tablets and the research group treated with nifedipine controlled-release tablets combined with valsartan. The therapeutic effects of the two groups of patients were compared and analyzed. Compared with the control group (82.22%), the total treatment effective rate of the research group (95.56%) was higher, p<0.05. Comparing the blood pressure level before and after treatment of the two groups, the improvement effect of the research group after treatment was more obvious, p<0.05. The incidence of adverse reactions was 6.67% in the research group, which was significantly lower than that (20.00%) in the control group, p<0.05. The application of nifedipine controlled-release tablets combined with valsartan in the treatment of patients with primary hypertension can significantly improve the therapeutic effect of patients, and has good safety and reliability, which is a treatment mode worthy of promotion and practice.


Assuntos
Hipertensão/tratamento farmacológico , Nifedipino/uso terapêutico , Valsartana/uso terapêutico , Idoso , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/uso terapêutico , Bloqueadores dos Canais de Cálcio/administração & dosagem , Bloqueadores dos Canais de Cálcio/uso terapêutico , Preparações de Ação Retardada , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nifedipino/administração & dosagem , Valsartana/administração & dosagem
14.
J Immunol ; 194(1): 429-37, 2015 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-25429070

RESUMO

Hemorrhage is a common clinical manifestation in patients with cancer. Intratumor hemorrhage has been demonstrated to be a poor prognostic factor for cancer patients. In this study, we investigated the role of RBCs and hemoglobin (Hb) in the process of tumor progression and therapeutical response. RBCs and Hb potently promoted tumor cell proliferation and syngenic tumor growth. RBCs and Hb activated the reactive oxygen species-NF-κB pathway in both tumor cells and macrophages. RBCs and Hb also induced chemoresistance mediated, in part, by upregulating ABCB1 gene expression. Tumor growth induced by RBCs was accompanied by an inflammatory signature, increased tumor vasculature, and influx of M2 macrophages. In both the peritoneal cavity and tumor microenvironment, extravascular RBCs rapidly recruited monocyte-macrophages into the lesion sites. In addition, RBCs and Hb increased several nucleotide-binding oligomerization domain-like receptors' expression and induced IL-1ß release. Our results provide novel insights into the protumor function of RBCs and Hb as endogenous danger signals, which can promote tumor cell proliferation, macrophage recruitment, and polarization. Hemorrhage may represent a useful prognostic factor for cancer patients because of its role in tumor promotion and chemoresistance.


Assuntos
Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Eritrócitos/patologia , Hemoglobinas/farmacologia , Hemorragia/patologia , Neoplasias/patologia , Subfamília B de Transportador de Cassetes de Ligação de ATP/biossíntese , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Animais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Movimento Celular/imunologia , Proliferação de Células , Cisplatino/farmacologia , Doxorrubicina/farmacologia , Inflamação/imunologia , Interleucina-1beta/metabolismo , Macrófagos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neoplasias/irrigação sanguínea , Neoplasias/tratamento farmacológico , Neovascularização Patológica , Estresse Oxidativo/efeitos dos fármacos , Paclitaxel/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Fator de Transcrição RelA/biossíntese , Fator de Transcrição RelA/metabolismo , Microambiente Tumoral/imunologia
15.
Tumour Biol ; 37(6): 7213-27, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26666817

RESUMO

Stem cell factor (SCF) plays an important role in tumor growth and metastasis. However, the function of SCF in regulating stemness and migration of cancer stem cells (CSCs) remains largely undefined. Here, we report that non-adhesive culture system can enrich and expand CSCs derived from Lewis lung carcinoma (LLC) cells and that the expression level of SCF in CSCs was higher than those in LLC cells. Silencing SCF via short hairpin (sh) RNA lentivirus transduction attenuated sphere formation and inhibited expressions of stemness genes, ALDH1, Sox2, and Oct4 of CSCs in vitro and in vivo. Moreover, SCF-silenced CSCs inhibited the migration and epithelial-mesenchymal transition, with decreased expression of N-cadherin, Vimentin, and increased expression of E-cadherin in vitro and in vivo. Finally, SCF-short hairpin RNA (shRNA) lentivirus transduction suppressed tumorigenicity of CSCs. Taken together, our findings unraveled an important role of SCF in CSCs derived from LLC cells. SCF might serve as a novel target for lung cancer therapy.


Assuntos
Carcinoma Pulmonar de Lewis/patologia , Movimento Celular/efeitos dos fármacos , Transição Epitelial-Mesenquimal , Inativação Gênica , Células-Tronco Neoplásicas/patologia , Fator de Células-Tronco/metabolismo , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Adipócitos/patologia , Família Aldeído Desidrogenase 1 , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Biomarcadores Tumorais/metabolismo , Western Blotting , Carcinoma Pulmonar de Lewis/tratamento farmacológico , Carcinoma Pulmonar de Lewis/metabolismo , Diferenciação Celular , Proliferação de Células/efeitos dos fármacos , Feminino , Imunofluorescência , Técnicas Imunoenzimáticas , Isoenzimas/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , RNA Interferente Pequeno/genética , Retinal Desidrogenase/metabolismo , Fator de Células-Tronco/antagonistas & inibidores , Fator de Células-Tronco/genética , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Cancer Cell Int ; 14(1): 24, 2014 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-24602316

RESUMO

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a common malignancy in China and Southeast Asia. Radiotherapy is the major treatment modality for patients with NPC, but does not always achieve fully satisfactory outcomes. Studies have shown that epidermal growth factor receptor (EGFR) is highly expressed in NPC, and EGFR-targeted treatment is expected to be a new strategy for NPC. Recently, clinical trials have shown that NPC patients have different responses to gefitinib. Thus, the identification of indicators that can regulate and predict the sensitivity of NPC to gefitinib is very valuable. MiRNAs (MicroRNAs) are closely related to cancer development. We studied miRNAs in NPC cell lines to identify those that can regulate and predict the effectiveness of gefitinib on NPC. METHODS: CCK8, Annexin V-FITC assays and animal models were carried out to evaluate the inhibitory effect of gefitinib on NPC cell lines HNE-1 and HK-1. MiRNA microarrays were used to detect and compare the miRNAs expression levels in the two cells with gefitinib or not, and qRT-PCR was used to evaluate miR-125a-5p expression in NPC cells and in serum of the tumor animal models. Loss-of-function and gain-of-function experiments were taken to evaluate the effect of miR-125a-5p on gefitinib effectiveness. Western blots were used to evaluate the effect of miR-125a-5p on p53 and Her2 in HNE-1 and HK-1 cells. RESULTS: Gefitinib inhibited two NPC cell lines proliferation in vitro and in vivo,and HNE-1 cells were less sensitive than HK-1 cells to gefitinib.MiR-125a-5p expression levels were increased by geftinib in the two cell lines and in the serum of NPC tumor bearing-mice. This phenomenon was weak in HNE-1 cells and strong in HK-1 cells. MiR-125a-5p over expression improved anti-proliferative and pro-apoptotic effects of gefitinib on the NPC cells and that miR-125a-5p down-regulation decreased those effects. MiR-125a-5p also increased p53 protein expression in HNE-1 cells, and decreased Her2 protein expression in HNE-1 and HK-1 cells. CONCLUSIONS: Our results indicate that gefitinib sensitivity and some miRNAs expressions varied in NPC cell lines. The miR-125a-5p is a possible candidate that can regulate and predict the effect of gefitinib on NPC.

17.
Anal Biochem ; 447: 156-61, 2014 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-24189207

RESUMO

In this study, we report an approach to activate inert hydrocarbon monolayers with ultraviolet (UV) light to fabricate DNA microarrays. Unlike traditional microarrays that require reactive functional groups on the surface, our DNA microarray is built on an inert layer of N,N-dimethyl-N-octadecyl(3-aminopropyl)trimethoxysilyl chloride silane (DMOAP). This layer is activated by UV (254 nm) just prior to the immobilization of oligonucleotide probes. Our X-ray photoelectron spectroscopy (XPS) results show that new functional groups such as alcohol (C--O), aldehyde (C=O), and carboxylic acid (O--C=O) form on the surface after the UV exposure. Among them, aldehyde groups are responsible for the immobilization of amine-label oligonucleotides. By using this approach, we further optimize UV exposure time and oligonucleotide concentration and also reduce agent concentration to achieve a high density of immobilized oligonucleotides up to 0.16 pmol/mm². As a proof of concept, we demonstrate that this microarray can be used for differentiation of different Clostridium species such as Clostridium acetobutylicum, Clostridium butylicum, and Clostridium beijerinkii.


Assuntos
Clostridium/genética , Clostridium/isolamento & purificação , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Raios Ultravioleta , Vidro/química , Hibridização de Ácido Nucleico , Sondas de Oligonucleotídeos/química , Sondas de Oligonucleotídeos/genética , Silanos/química , Propriedades de Superfície , Fatores de Tempo
18.
Front Immunol ; 15: 1386561, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38957460

RESUMO

Targeted therapy and immunotherapy are both important in the treatment of non-small-cell lung cancer (NSCLC). Accurate diagnose and precise treatment are key in achieving long survival of patients. MET fusion is a rare oncogenic factor, whose optimal detection and treatment are not well established. Here, we report on a 32-year-old female lung adenocarcinoma patient with positive PD-L1 and negative driver gene detected by DNA-based next-generation sequencing (NGS). A radical resection of the primary lesion after chemotherapy combined with PD-1 checkpoint inhibitor administration indicated primary immuno-resistance according to her pathological response and rapid relapse. A rare CD47-MET was detected by RNA-based NGS, which was confirmed by fluorescence in situ hybridization. Multiplex immunofluorescence revealed a PD-L1 related heterogeneous immunosuppressive microenvironment with little distribution of CD4+ T cells and CD8+ T cells. Savolitinib therapy resulted in a progression-free survival (PFS) of >12 months, until a new secondary resistance mutation in MET p.D1228H was detected by re-biopsy and joint DNA-RNA-based NGS after disease progression. In this case, CD47-MET fusion NSCLC was primarily resistant to immunotherapy, sensitive to savolitinib, and developed secondary MET p.D1228H mutation after targeted treatment. DNA-RNA-based NGS is useful in the detection of such molecular events and tracking of secondary mutations in drug resistance. To this end, DNA-RNA-based NGS may be of better value in guiding precise diagnosis and individualized treatment in this patient population.


Assuntos
Adenocarcinoma de Pulmão , Sequenciamento de Nucleotídeos em Larga Escala , Neoplasias Pulmonares , Proteínas Proto-Oncogênicas c-met , Humanos , Feminino , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/diagnóstico , Adenocarcinoma de Pulmão/imunologia , Adenocarcinoma de Pulmão/terapia , Adulto , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/terapia , Proteínas Proto-Oncogênicas c-met/genética , Proteínas de Fusão Oncogênica/genética , Resistencia a Medicamentos Antineoplásicos/genética , Inibidores de Checkpoint Imunológico/uso terapêutico
19.
Asian J Surg ; 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38942631

RESUMO

Distal gastrectomy (DG) with lymph node dissection for gastric cancer is routinely performed. In this meta-analysis, we present an updated overview of the perioperative and oncological outcomes of laparoscopic DG (LDG) and robotic DG (RDG) to compare their safety and overall outcomes in patients undergoing DG. An extensive search was conducted using the MEDLINE, EMBASE, PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials from the establishment of the database to June 2023 for randomized clinical trials comparing RDG and LDG. The primary outcome was operative results, postoperative recovery, complications, adequacy of resection, and long-term survival. We identified twenty studies, evaluating 5,447 patients (1,968 and 3,479 patients treated with RDG and LDG, respectively). We observed no significant differences between the two groups in terms of the proximal resection margin, number of dissected lymph nodes, major complications, anastomosis site leakage, time to first flatus, and length of hospital stay. The RDG group had a longer operative time (P < 0.00001), lesser bleeding (P = 0.0001), longer distal resection margin (P = 0.02), earlier time to oral intake (P = 0.02), fewer overall complications (P = 0.004), and higher costs (P < 0.0001) than the LDG group. RDG is a promising approach for improving LDG owing to acceptable complications and the possibility of radical resection. Longer operative times and higher costs should not prevent researchers from exploring new applications of robotic surgery.

20.
Ultrason Sonochem ; 107: 106888, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38697875

RESUMO

Microbubble-mediated therapeutic gene or drug delivery is a promising strategy for various cardiovascular diseases (CVDs), but the efficiency and precision need to be improved. Here, we propose a cavitation bubble-driven drug delivery strategy that can be applied to CVDs. A bubble-pulse-driving theory was proposed, and the formula of time-averaged thrust driven by bubble pulses was derived. The continuous motion of particles propelled by cavitation bubbles in the ultrasonic field is investigated experimentally by high-speed photography. The cavitation bubbles grow and collapse continuously, and generate periodic pulse thrust to drive the particles to move in the liquid. Particles attached to bubbles will move in various ways, such as ejection, collision, translation, rotation, attitude variation, and circular motion. The cavity attached to the particle is a relatively large cavitation bubble, which does not collapse to the particle surface, but to the axis of the bubble perpendicular to the particle surface. The cavitation bubble expands spherically and collapses asymmetrically, which makes the push on the particle generated by the bubble expansion greater than the pull on the particle generated by the bubble collapse. The time-averaged force of the cavitation bubble during its growth and collapse is the cavitation-bubble-driven force that propels the particle. Both the cavitation-bubble-driven force and the primary Bjerknes force act in the same position on the particle surface, but in different directions. In addition to the above two forces, particles are also affected by the mass force acting on the center of mass and the motion resistance acting on the surface, so the complex motion of particles can be explained.

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