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1.
Anal Chem ; 96(12): 4997-5005, 2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38483157

ABSTRACT

In the realm of clinical practice, the concurrent utilization of anticancer medications can enhance their overall therapeutic efficacy. However, it is crucial to acknowledge that the interactions among these anticancer drugs can potentially yield detrimental consequences on their intended outcomes. Consequently, the assessment of both anticancer potency and potential toxic side effects is greatly refined when multiple anticancer drugs are simultaneously detected and evaluated. Here, we designed a wearable electrochemical aptasensor array for monitoring multiple anticancer drugs in sweat. The integrated sensor array consists of three working electrodes modified with three different aptamers (Apt1, Apt2, and Apt3), a Au counter electrode, and a Ag/AgCl reference electrode. Molecular docking simulations were performed to show the binding affinities between three anticancer drugs and their corresponding aptamers. Various eigenvalues were derived from the square-wave voltammetry electrochemical signals, and these data sets were subjected to rigorous analysis through multivariate data analysis techniques. This analytical approach demonstrated exceptional performance by achieving flawless 100% accuracy in the precise identification of nine anticancer drugs consistently at uniform concentrations. Furthermore, the integrated wearable sensor array exhibited impressive capabilities, correctly recognizing all nine anticancer drugs with 100% accuracy and successfully distinguishing between these drugs in artificial sweat samples. The proposed sensor array presents good stability for 15 days. Flexibility tests showed stable device performance after 500 twisting cycles. This innovative wearable sensing array represents a novel approach for achieving real-time monitoring and precise adjustment of drug dosages. It offers invaluable insights for tailoring the treatment of anticancer drugs to individual patients, predicting both drug efficacy and potential adverse reactions within the field of clinical medicine.


Subject(s)
Biosensing Techniques , Sweat , Humans , Sweat/chemistry , Molecular Docking Simulation , Electrodes , Oligonucleotides/analysis , Electrochemical Techniques
2.
Anal Chem ; 96(3): 1205-1213, 2024 01 23.
Article in English | MEDLINE | ID: mdl-38191284

ABSTRACT

Sweat has emerged as a compelling analyte for noninvasive biosensing technology because it contains a wealth of important biomarkers in hormones, organic biomacromolecules, and various ionic mixtures. These components offer valuable insights and can reflect an individual's physiological conditions. Here, we introduced an explainable deep learning (DL)-assisted wearable self-calibrating colorimetric biosensing analysis platform to efficiently and precisely detect the biomarker's concentration in sweat. Specifically, we have integrated the advantages of the colorimetric sensing method, adsorbing-swelling hydrogel, and explainable DL algorithms to develop an enzyme/indicator-immobilized colorimetric patch, which has reliable colorimetric sensing ability and excellent adsorbing-swelling function. A total of 5625 colorimetric images were collected as the analysis data set and assessed two DL algorithms and seven machine learning (ML) algorithms. Zn2+, glucose, and Ca2+ in human sweats could be facilely classified and quantified with 100% accuracy via the convolutional neural network (CNN) model, and the testing results of actual sweats via the DL-assisted colorimetric approach are 91.7-97.2% matching with the classical UV-vis spectrum. Class activation mapping (CAM) was utilized to visualize the inner working mechanism of CNN operation, which contributes to verify and explicate the design rationality of the noninvasive biosensing technology. An "end-to-end" model was established to ascertain the black box of the DL algorithm, promoted software design or principium optimization, and contributed facile indicators for health monitoring, disease prevention, and clinical diagnosis.


Subject(s)
Deep Learning , Humans , Sweat , Colorimetry , Neural Networks, Computer , Algorithms
3.
J Shoulder Elbow Surg ; 33(5): e248-e260, 2024 May.
Article in English | MEDLINE | ID: mdl-38182026

ABSTRACT

BACKGROUND: Traumatic coronoid deficiency with persistent elbow instability is a challenging condition. Autologous bone graft reconstruction is often associated with a range of additional clinical problems and the outcome is often unpredictable. The purpose of this study was to design a prosthetic device that can reconstruct coronoid deficiency of any height and to evaluate its mechanical properties using finite element analysis. MATERIALS AND METHODS: A customized coronoid prosthesis was designed based on image registration, automatic measurement, and computer-aided design. After pilot study and sample size calculation, image data collected from 6 patients who underwent bilateral complete upper extremity CT scans were reconstructed. The test was divided into 3 groups: coronoid intact, prosthesis and autograft. Regan-Morrey type II and autologous olecranon osteotomy models were established. The prosthesis and autogenous olecranon were assembled to the coronoid base. Stress was applied axially along the proximal humeral diaphysis and implant micromotion and contact mechanics of the humeroulnar joint were measured at 30°, 45°, 60° and 90° of joint flexion respectively. RESULTS: At all flexion angles, the maximum stress on the coronoid articular surface was significantly reduced in the prosthesis and autograft groups, with the reduction being more significant in the latter (P < .001). With increasing flexion, the maximum stress at the coronoid articular surface increased significantly after autograft reconstruction (7.2 to 68 MPa, P < .001), whereas the humeroulnar joint obtained a similar contact mechanics pattern to that of the control group after prosthetic reconstruction. As the flexion angle increased, the relative micromotion of both the prosthesis and autograft increased significantly (0.5-1.6 vs. 0.2-1.2, Pmeasure time < 0.001, Pgroups < 0.001). Contact pressure and center-of-force paths of the humeroulnar joint experience abrupt stress changes at approximately 60° of flexion. CONCLUSION: The contact stress pattern in the humeroulnar joint is similar in prosthesis and intact coronoid groups. Autograft reconstruction increases contact stresses at the articular surface and alters the joint center-of-force path. The "stress surge phenomenon" in the humeroulnar joint surface before and after 60° of flexion may be one of the mechanisms of traumatic elbow degeneration.


Subject(s)
Elbow Joint , Joint Instability , Humans , Elbow Joint/diagnostic imaging , Elbow Joint/surgery , Joint Instability/diagnostic imaging , Joint Instability/etiology , Joint Instability/surgery , Finite Element Analysis , Pilot Projects , Prostheses and Implants , Range of Motion, Articular
4.
iScience ; 26(11): 108298, 2023 Nov 17.
Article in English | MEDLINE | ID: mdl-38026179

ABSTRACT

Reliable monitoring the movement amplitude and dynamics during sports exercise is significant for improving training results and preventing training wound. Here, we present a printed perovskite-based photodetector for real-time and quantitative monitoring of sports motion. The ordered nucleation and growth of perovskite crystals are regulated by the 4-acetamidothiophenol (AMTP) at the interface, which promotes the size of perovskite crystals into the micrometer. Benefiting from the uniformity of the AMTP-regulated MAPbI3, the as-prepared photodetector gives great photocurrent response under indoor light or outdoor light. During the exercise, real-time monitoring sports motion is achieved through detecting the illumination changing of photodetectors attaching on the wrist and ankles. Moreover, twelve kinds of common sports can be quantitatively analyzed with the detection of illumination changing on the photodetector. Such photodetector provides an efficient measurement method of wearable electronics for sports monitoring.

5.
Mater Today Bio ; 20: 100675, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37304579

ABSTRACT

In recent years, immune checkpoint blockades (ICBs) have made great progress in the treatment of cancer. However, most ICBs have not yet been observed to be satisfactory in the treatment of osteosarcoma. Herein, we designed composite nanoparticles (NP-Pt-IDOi) from a reactive oxygen species (ROS) sensitive amphiphilic polymer (PHPM) with thiol-ketal bonds in the main chain to encapsulate a Pt(IV) prodrug (Pt(IV)-C12) and an indoleamine-(2/3)-dioxygenase (IDO) inhibitor (IDOi, NLG919). Once NP-Pt-IDOi enter the cancer cells, the polymeric nanoparticles could dissociate due to the intracellular ROS, and release Pt(IV)-C12 and NLG919. Pt(IV)-C12 induces DNA damage and activates the cGAS-STING pathway, increasing infiltration of CD8+ T cells in the tumor microenvironment. In addition, NLG919 inhibits tryptophan metabolism and enhances CD8+ T cell activity, ultimately activating anti-tumor immunity and enhancing the anti-tumor effects of platinum-based drugs. NP-Pt-IDOi were shown to have superior anti-cancer activity in vitro and in vivo in mouse models of osteosarcoma, providing a new clinical paradigm for combining chemotherapy with immunotherapy for osteosarcoma.

6.
Sci Rep ; 13(1): 2473, 2023 Feb 11.
Article in English | MEDLINE | ID: mdl-36774390

ABSTRACT

Based on the digital elevation data, snow depth and snow cover remote sensing data, this paper divides six snow evolution areas and geographical partitions, extracts the geographical partitions of each evolution area and obtains the geographical characteristics of the evolution area for analysis. The results show that: (1) From 2003 to 2017, the average snow area decreased at a rate of - 0.004, and the average snow depth increased at a rate of 0.03. (2) The snow in the middle altitude hill with shady gentle slope area is the most obvious in the seasonal evolution, and the percentage of this region in the seasonal snow evolution area is 5.46%, the snow depth in the middle altitude hill with sunny and gentle slopes area increased and decreased significantly in the past 15 years, and the percentage of this region in the SD significant changes evolution area was 6.32%. The snow in the low relief middle altitude mountain with shady and moderate slope area not only shows obvious seasonal evolution, but also increases and decreases significantly in snow depth. And the percentage of this region in the seasonal snow significant evolution area is 5.82%. (3) The geographical partitions with the largest area in all evolution areas is the middle altitude hill with sunny and gentle slopes area (4.75%). (4) The geographical partition with the largest variation of snow depth in Tianshan region is the low relief middle altitude mountain with shady and moderate slope area (12.02 cm). (5) The snow accumulation and melting are obvious in the range of 1000-3500 m above altitude, different geomorphology types lead to obvious differences in snow characteristics. The snow melting is most obvious in the gentle slope area of the low topographic relief geomorphology types, and the snow accumulation is most obvious in the steep slope area of the middle relief geomorphology types.

7.
Rev. bras. med. esporte ; 28(6): 782-784, Nov.-Dec. 2022. tab
Article in English | LILACS | ID: biblio-1376775

ABSTRACT

ABSTRACT Introduction Ankle injury is an acute soft tissue pathology where the ankle ligaments are distended, lacerated, or ruptured due to violence during sport. This joint is also one of the most vulnerable in sports. After an injury, immediate and adequate care is significant in reducing pain and complication. Objective Statistically analyze the sports injuries of the ankle cases, determining the principal reasons for injury and outlining preventive measures. Methods A statistical investigation on the sports injuries of 275 Qiqihar higher education students was performed with questionnaires and teaching practice methods. The research was focused on the injured structures and the injury causes analysis. In parallel, corresponding proposals aimed at preventing these sports injuries were raised. Results Joint injuries and ankle sprains followed by hematomas represented the most significant proportion of ankle injuries. The reasons are lack of physical fitness, lack of awareness of self-protection, inadequate preparation in the sporting environment facilities, and performing tasks outside what the superior specified was specified. Conclusion Medical work needs to increase dissemination so that people realize the causes of sports injuries. At the same time, it helps people master the care measures before and after the injury. This reduces the incidence of sports injuries and reduces the occurrence of complications. Evidence level II; Therapeutic Studies - Investigating the results.


RESUMO Introdução A lesão no tornozelo é uma patologia aguda dos tecidos moles na qual os ligamentos do tornozelo são distendidos, lacerados, ou rompidos devido a violência durante o esporte. Essa articulação é também uma das mais vulneráveis nos esportes. Depois de uma lesão, o cuidado imediato e correto é significativo para aliviar a dor e reduzir complicações. Objetivo Analisar estatisticamente os casos de lesões esportivas do tornozelo, levantando as principais razões de lesão e traçar condutas preventivas. Métodos Uma investigação estatística sobre as lesões esportivas de 275 estudantes do ensino superior de Qiqihar foi executada com questionário e métodos de prática de ensino. A pesquisa foi concentrada na análise das estruturas lesionadas e a causa da lesão. Paralelamente foram levantadas propostas correspondentes visando a prevenção dessas lesões esportivas. Resultados As lesões articulares e entorses do tornozelo seguidas por hematomas representaram a maior proporção de lesões no tornozelo. Dentre os motivos, destacaram-se a falta de preparo físico, falta de consciência de autoproteção, preparação inadequada nas instalações do ambiente esportivo e execuções de tarefas fora do especificado pelo superior. Conclusão O trabalho médico precisa aumentar a divulgação para que as pessoas percebam as causas das lesões esportivas. Ao mesmo tempo, ajuda as pessoas a dominar as medidas de cuidado antes e depois da lesão. Isso reduz a incidência de lesões esportivas e reduz a ocorrência de complicações. Nível de evidência II; Estudos terapêuticos - Investigação de resultados.


RESUMEN Introducción La lesión de tobillo es una patología aguda de las partes blandas en la que los ligamentos del tobillo se distienden, desgarran o rompen debido a la violencia durante la práctica deportiva. Esta articulación es también una de las más vulnerables en el deporte. Después de una lesión, una atención rápida y correcta es importante para aliviar el dolor y reducir las complicaciones. Objetivo Analizar estadísticamente los casos de lesiones esporádicas del tobillo, levantando las principales causas de lesión y trazar conductas preventivas. Métodos Se realizó una investigación estadística sobre las lesiones deportivas de 275 estudiantes de educación superior en Qiqihar con métodos de cuestionario y práctica docente. La investigación se centró en el análisis de las estructuras lesionadas y la causa de la lesión. Paralelamente, se plantearon las correspondientes propuestas encaminadas a la prevención de estas lesiones deportivas. Resultados Las lesiones articulares y los esguinces de tobillo, seguidos de los hematomas, representaron la mayor proporción de lesiones de tobillo. Entre los motivos, destacaron la falta de preparación física, la falta de conciencia de autoprotección, la preparación inadecuada en las instalaciones del entorno deportivo y la ejecución de tareas fuera de lo especificado por el superior. Conclusión El trabajo médico debe aumentar la difusión para que la gente se dé cuenta de las causas de las lesiones deportivas. Al mismo tiempo, ayuda a las personas a dominar las medidas de cuidado antes y después de la lesión. Esto reduce la incidencia de las lesiones deportivas y disminuye la aparición de complicaciones. Nivel de evidencia II; Estudios terapéuticos - Investigación de resultados.


Subject(s)
Humans , Male , Female , Athletic Injuries/nursing , Physical Fitness/physiology , Ankle Injuries/nursing
8.
Lab Chip ; 22(16): 3008-3014, 2022 08 09.
Article in English | MEDLINE | ID: mdl-35781479

ABSTRACT

Designing and preparing a fast and easy-to-use immunosensing biochip are of great significance for clinical diagnosis and biomedical research. In particular, sensitive, specific, and early detection of biomarkers in trace samples promotes the application of point-of-care testing (POCT). Here, we demonstrate an all-printed immunosensing biochip with the characteristics of hydrodynamic enrichment and photonic crystal-enhanced fluorescence. Direct quantitative detection of cardiac biomarkers via one drop of blood is achieved in 10 min. After simulating the hydrodynamic behavior of one droplet serum on the printed assay, creatine kinase-MB (CK-MB) has been recognized and located on the photonic crystal arrays. Benefiting from the fluorescence enhancement effect, quantitative detection of CK-MB has been demonstrated from 0.01 ng ml-1 to 100 ng ml-1, which is superior to the conventional enzyme-linked immunosorbent assay (ELISA). This strategy provides a general and easy-to-use approach for fast quantitative detection of biomarkers, which would be improved further for portable clinical diagnostics and home medical monitoring.


Subject(s)
Myocardial Infarction , Point-of-Care Systems , Biomarkers , Creatine Kinase, MB Form , Enzyme-Linked Immunosorbent Assay , Humans
9.
Ann Transl Med ; 8(21): 1453, 2020 Nov.
Article in English | MEDLINE | ID: mdl-33313198

ABSTRACT

BACKGROUND: To explore the performance status of Chinese postgraduate medical students in literature searching. METHODS: A self-designed online questionnaire was used to assess the literature search performance of postgraduate students (PGSs) from the classes of 2016, 2017, 2018, and 2019 from two medical colleges. The items of the questionnaire mainly included: the demographic characteristics of the PGSs, methods of literature review, literature reading habits, and use of literature. We also designed a self-assessed score that ranged from the lowest 1 point to the highest 5 points. RESULTS: A total of 902 PGSs (482 male, average age: 29.4±5.8 years old, working time range: 0-10 years, average 3.7±2.4 years) completed the questionnaire. Most PGSs investigated literature only at the work tasks (632, 70.1%) and writing papers (571, 63.3%) stages. Of the PGSs, 542 (60.1%) PGSs searched literature frequency (≥1 paper/week), and 114 (12.6%) did not perform advanced searches, and some had no knowledge of advanced search techniques at all. Most PGSs had not read more than 100 Chinese articles or English articles before. Most PGSs were used to read articles from the most authoritative journals (665, 73.7%) or high impact factor (IF) (540, 59.9%). PGSs (845, 93.7%) only read the full text of articles they deemed important. Of the PGSs, 441 (48.9%) did not use literature management tools. For self-assessed score of literature searching and reading skills, the mean was 2.1 (standard deviation, 0.8). Reading literature efficiently (710, 78.7%) and tracking recent literatures (615, 68.2%) were the two needed literature skills reported. CONCLUSIONS: Chinese medical PGSs still have room for improvement in relation to literature investigation. Intensive training in literature searching should be given to improve their performance.

11.
Acta Otolaryngol ; 140(8): 664-667, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32400245

ABSTRACT

Background: The potential influence of Eustachian tube dysfunction (ETD) on the efficacy of tympanoplasty is controversial.Objective: This study aims to investigate the correlation between Eustachian tube function (ETF) and outcomes of type I tympanoplasty for chronic suppurative otitis media (CSOM).Materials and Methods: 53 patients with CSOM and receiving type I tympanoplasty were divided into a dysfunction group (Eustachian tube score; ETS ≤ 5points) and a normal group (ETS > 5 points) according to their preoperative ETS. During the one-year follow-up, the ETS, hearing results, and eardrum condition of the patients were recorded and analyzed.Results: The ETS improved significantly from 2.57 (±1.73SD) to 4.68 (±2.00SD), while the mean air-bone gap (ABG) decreased significantly from 20.94 (±9.04SD) dB to 16.43 (±9.06SD) dB in the dysfunction group (p < .05). The postoperative ABG showed no significant difference in the two groups. The healing rate of the tympanic membrane was 96.43% in the dysfunction group, and 100% in the normal group.Conclusions and significance: The ETF was significantly improved after type I tympanoplasty for CSOM combined with ETD, and the postoperative efficacy was not adversely affected. The ETD may not influence the outcomes of type I tympanoplasty for CSOM.


Subject(s)
Eustachian Tube/physiopathology , Otitis Media, Suppurative/surgery , Tympanoplasty/methods , Adult , Aged , Audiometry, Pure-Tone , Female , Follow-Up Studies , Humans , Male , Middle Aged , Otitis Media, Suppurative/physiopathology
12.
Br J Cancer ; 122(12): 1837-1847, 2020 06.
Article in English | MEDLINE | ID: mdl-32350414

ABSTRACT

BACKGROUND: Stearoyl-CoA desaturase-1 (SCD1) is reported to play essential roles in cancer stemness among several cancers. Our previous research revealed significant overexpression of SCD1 in primary gastric cancer stem cells (GCSCs), with its functional role still unknown. METHODS: We stably established three primary GCSCs by sphere-forming assays and flow cytometry. Protein quantification and bioinformatics analysis were performed to reveal the differential protein pattern. Lentivirus-based small-interfering RNA (siRNA) knockdown and pharmacological inhibition approaches were used to characterise the function and molecular mechanism role of SCD1 in the regulation of GC stemness and tumour metastasis capacity both in vitro and in vivo. RESULTS: SCD1 was found to increase the population of GCSCs, whereas its suppression by an SCD1 inhibitor or knockdown by siRNA attenuated the stemness of GCSCs, including chemotherapy resistance and sphere-forming ability. Furthermore, SCD1 suppression reversed epithelial-to-mesenchymal transition and reduced the GC metastasis probability both in vitro and in vivo. Downregulation of SCD1 in GCSCs was associated with the expression of Yes-associated protein (YAP), a key protein in the Hippo pathway, and nuclear YAP translocation was also blocked by the SCD1 decrease. CONCLUSIONS: SCD1 promotes GCSC stemness through the Hippo/YAP pathway. Targeting SCD1 might be a novel therapeutic strategy, especially to suppress GC metastasis and sensitise chemotherapy.


Subject(s)
Adenocarcinoma/pathology , Neoplastic Stem Cells/pathology , Stearoyl-CoA Desaturase/metabolism , Stomach Neoplasms/pathology , Adaptor Proteins, Signal Transducing/metabolism , Adenocarcinoma/metabolism , Animals , Heterografts , Hippo Signaling Pathway , Humans , Male , Mice , Mice, SCID , Neoplasm Invasiveness/pathology , Neoplasm Metastasis , Neoplastic Stem Cells/metabolism , Protein Serine-Threonine Kinases/metabolism , Signal Transduction/physiology , Stomach Neoplasms/metabolism , Transcription Factors/metabolism , Tumor Cells, Cultured , YAP-Signaling Proteins
13.
J Cell Physiol ; 235(3): 2847-2856, 2020 03.
Article in English | MEDLINE | ID: mdl-31535369

ABSTRACT

Septic cardiomyopathy is associated with mitochondrial damage and endoplasmic reticulum (ER) dysfunction. However, the upstream mediator of mitochondrial injury and ER stress has not been identified and thus little drug is available to treat septic cardiomyopathy. Here, we explored the role of B-cell receptor-associated protein 31 (BAP31) in septic cardiomyopathy and figure out whether melatonin could attenuate sepsis-mediated myocardial depression via modulating BAP31. Lipopolysaccharide (LPS) was used to establish the septic cardiomyopathy model. Pathway analysis was performed via western blot, quantitative polymerase chain reaction and immunofluorescence. Mitochondrial function and ER stress were detected via enzyme-linked immunosorbent assay, western blot, and immunofluorescence. After exposure to LPS, cardiac function was reduced due to excessive inflammation response and extensive cardiomyocyte death. Mechanistically, melatonin treatment could dose-dependently improve cardiomyocyte viability via preserving mitochondrial function and reducing ER stress. Further, we found that BAP31 transcription was repressed by LPS whereas melatonin could restore BAP31 expression; this effect was dependent on the MAPK-ERK pathway. Inhibition of the ERK pathway and/or knockdown of BAP31 could attenuate the beneficial effects of melatonin on mitochondrial function and ER homeostasis under LPS stress. Altogether, our results indicate that ERK-BAP31 pathway could be used as a critical mediator for mitochondrial function and ER homeostasis in sepsis-related myocardial injury. Melatonin could stabilize BAP31 via the ERK pathway and thus contribute to the preservation of cardiac function in septic cardiomyopathy.


Subject(s)
Cardiomyopathies/drug therapy , Endoplasmic Reticulum Stress/drug effects , Melatonin/pharmacology , Membrane Proteins/drug effects , Signal Transduction/drug effects , Animals , Cardiomyopathies/metabolism , Endoplasmic Reticulum/drug effects , Endoplasmic Reticulum/metabolism , Lipopolysaccharides/pharmacology , Male , Membrane Proteins/metabolism , Mice , Mitochondria/drug effects , Mitochondria/metabolism , Mitogen-Activated Protein Kinase Kinases/drug effects , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/metabolism , Up-Regulation/drug effects
14.
RSC Adv ; 9(70): 40924-40932, 2019 Dec 09.
Article in English | MEDLINE | ID: mdl-35540090

ABSTRACT

To understand protein structural transition and ß-sheet formation is of importance in disparate areas such as silk protein processing and disease related ß-amyloid behavior. Herein, GAGSGAGAGSGAGY (GY-14), a tetradecapeptide based on the crystallizable sequence of silk fibroin, was employed as a model peptide of the crystalline regions of silk fibroin. Due to the incorporation of tyrosine (Y), GY-14 was able to reduce Au3+ to Au NPs and further stabilize them without any external reducing or capping reagents to produce GY-14 stabilized Au NPs (GY-14@Au NPs). The in situ prepared GY-14@Au NPs were utilized as a built-in colorimetric indicator. The influences of specified physiological factors including decreasing the pH, the addition of calcium ions and isopropanol treatment on the self-assembly behavior of GY-14@Au NPs in aqueous solution have been studied. On the basis of transmission electron microscopy (TEM), dynamic light scattering (DLS), atomic force microscopy (AFM), Fourier transform infrared (FT-IR) spectroscopy and circular dichroism (CD) measurements, the color changes and the UV-Vis absorption peak shift of GY-14@Au NPs were attributed to the conformational change of the GY-14 peptide. The colorimetric readout can be seen with the naked eye, providing an efficient indicator to study the conformational changes of peptides exposed to various environmental stimuli.

15.
Int J Oncol ; 50(5): 1601-1611, 2017 May.
Article in English | MEDLINE | ID: mdl-28339027

ABSTRACT

Prostate cancer is the second leading cause of cancer deaths among men in Western counties and has increased in incidence also in China in recent years. Although diagnosis modalities for primary prostate cancer have markedly improved, there are still no effective therapies for metastatic prostate cancer. SU6668 is an inhibitor of the tyrosine kinase activity of three angiogenic receptors VEGFR2, PDGFRß and FGFR1. There is strong experimental evidence that SU6668 can induce growth inhibition of various primary tumors. However, the function and molecular mechanism of SU6668 in prostate cancer has not been fully elucidated. In the present study, we found that SU6668 inhibited the proliferation and invasion of prostate cancer cells. Functional studies also demonstrated that SU6668 inhibited epithelial-mesenchymal transition in DU145 and LNCap cells. After treatment with SU6668, MTDH protein, which has been reported to be significantly overexpressed in many human tumor tissues, was downregulated in DU145 and LNCap cells. siRNA-mediated silencing of MTDH in prostate cancer cells decreased their proliferation and invasive capabilities, suggesting that SU6668 may inhibit cell proliferation and invasion of prostate cancer cells partly through downstream targeting of MTDH. Mechanistic investigations showed that AKT signaling pathway was inhibited after SU6668 treatment in prostate cancer cells. Moreover, a combination of SU6668 and PI3K-AKT pathway inhibitor LY29004 resulted in increased inhibition of cell proliferation and invasion in DU145 cells. Taken together, our findings revealed that SU6668 suppressed prostate cancer progression by downregulating MTDH/AKT signaling pathway and identified a promising therapeutic strategy for prostate cancer.


Subject(s)
Angiogenesis Inhibitors/administration & dosage , Cell Adhesion Molecules/biosynthesis , Prostatic Neoplasms/drug therapy , Proto-Oncogene Proteins c-akt/biosynthesis , Cell Adhesion Molecules/genetics , Cell Line, Tumor , Cell Proliferation/drug effects , Disease Progression , Gene Expression Regulation, Neoplastic/drug effects , Humans , Indoles/administration & dosage , Male , Membrane Proteins , Neoplasm Invasiveness , Oxindoles , Propionates , Prostatic Neoplasms/genetics , Prostatic Neoplasms/pathology , Proto-Oncogene Proteins c-akt/genetics , Pyrroles/administration & dosage , RNA-Binding Proteins , Receptor, Fibroblast Growth Factor, Type 1/antagonists & inhibitors , Receptor, Platelet-Derived Growth Factor beta/antagonists & inhibitors , Signal Transduction/drug effects , Vascular Endothelial Growth Factor Receptor-2/antagonists & inhibitors
16.
Pharm Dev Technol ; 21(6): 680-7, 2016 Sep.
Article in English | MEDLINE | ID: mdl-25975585

ABSTRACT

Bone is among the most common sites of metastasis in cancer patients, so it is an urgent need to develop drug delivery systems targeting tumor bone metastasis with the feature of controlled release. This study aimed to delivery of thermosensitive liposomal doxorubicin to bone for tumor metastasis treatment. First, Brij78 (polyoxyethylene stearyl ether) was conjugated with Pamidronate (Pa). By incorporating Pa-Brij78 to DPPC/Chol liposomes, we developed Pa surface functionalized liposomes. The Pa-Brij78/DPPC/Chol liposomes (PB-liposomes) exhibited a stronger binding affinity to hydroxyapatite (HA), a major component of bone, than Brij78/DPPC/Chol liposomes (B-liposomes). Doxorubicin (Dox) was then encapsulated in PB-liposomes and the results demonstrated complete release of Dox from PB-liposomes or the complex of HA/PB-liposomes within 10 min at 42 °C. Next, human lung cancer A549 cells were treated with the thermosensitive complex of HA/PB-liposomes/Dox to mimic tumor bone metastasis treatment through bone targeted delivery of therapeutic agents. Pre-incubation of HA/PB-liposomes/Dox with mild heat at 42 °C induced subsequent higher cytotoxicity to A549 cells than incubation of the same complex at 37 °C, suggesting more active drug release triggered by heat. In conclusion, we synthesized a novel surfactant Pa-Brij78 and it has the potential to be used for development of a bone targeted thermosensitive liposome formulation for treatment of tumor bone metastasis.


Subject(s)
Bone Density Conservation Agents/chemical synthesis , Diphosphonates/chemical synthesis , Doxorubicin/analogs & derivatives , Drug Delivery Systems/methods , Surface-Active Agents/chemical synthesis , A549 Cells , Bone Density Conservation Agents/administration & dosage , Cell Survival/drug effects , Cell Survival/physiology , Chemistry, Pharmaceutical , Diphosphonates/administration & dosage , Dose-Response Relationship, Drug , Doxorubicin/administration & dosage , Doxorubicin/chemical synthesis , Humans , Polyethylene Glycols/administration & dosage , Polyethylene Glycols/chemical synthesis , Surface-Active Agents/administration & dosage , Temperature
17.
Materials (Basel) ; 7(8): 6028-6044, 2014 Aug 21.
Article in English | MEDLINE | ID: mdl-28788175

ABSTRACT

The purpose of the study was to develop a facile method for the fabrication of a stable and reusable magnetic graphene composite absorbent to remove trace levels of polybrominated diphenyl ethers in water treatment. The poly cationic Fe3O4@PDDA (poly(diallyldimethyl ammonium chloride) (PDDA)) core-shell structured nanoparticles were first synthesized, and then, DNA was laid on the surface of graphene oxide (GOx) to prepare the polyanionic GOx@DNA composite. The above materials were then mixed together and adhered together through sol-gel technology. Thus, the Fe3O4@PDDA/GOx@DNA composite absorbent was prepared. Its performance was tested by disperse solid phase extraction and gas chromatography/mass spectrometric (GC/MS) for removing six kinds of indicative polybrominated diphenyl ethers (BDEs) in water samples. The removal percentages of several real samples for six kinds of BDEs (BDE17, BDE28, BDE 71, BDE 47, BDE 66, BDE 100) at the ng/mL order of magnitude were in the range of 88.2%-99.1%. The removal percentage still reached 80.0% when the adsorbent was reused at least 20 times. The results suggested that the magnetic absorbent can obviously remove trace levels of BDEs from large volumes of aqueous solutions in environmental pollution cleanup with high removal efficiency.

18.
Inorg Chem ; 49(10): 4524-33, 2010 May 17.
Article in English | MEDLINE | ID: mdl-20408579

ABSTRACT

A series of 1,8-naphthyridine derivatives containing vinyl, 2-(2-acetylamino-pyridine-6-ethylene)-4-methyl-7-acetylamino-1,8-naphthyridine (L(1)), 2-(2-acetylamino-pyridine-6-ethylene)-1,8-naphthyridine (L(2)), 2-(2-acetylamino-pyridinyl-6-ethylene)-4-methyl-7-hydroxyl-1,8-naphthyridine (L(3)), 2-(2-diacetylamino-pyridinyl-3-ethylene)-7-diacetylamino-1,8-naphthyridine (L(4)), and 7-(2-diacetylamino-pyridinyl-3-ethylene)-4'-acetyl-pyrrolo[1',5'-a]-1,8-naphthyridine (L(5)), as well as complexes [CuL(1)(PCy(3))](BF(4))(2) (1) (PCy(3) = tricyclohexylphosphine), [Cu(2)L(1)(PPh(3))(4)](BF(4))(2) (2) (PPh(3) = triphenylphosphine), [Cu(2)L(1)(dppm)](BF(4))(2) (3) (dppm = bis(diphenylphosphino)methane), and [Cu(2)(L(1))(dcpm)][BF(4)](2) (4) (dcpm = bis(dicyclohexylphosphino)methane, were synthesized. All these compounds, except for L(1) and L(2), were characterized by single crystal X-ray diffraction analysis, and a comprehensive study of their spectroscopic properties involving experimental theoretical studies is presented. We found an intramolecular 1,3-hydrogen transfer during the formation of L(3) and L(4), which in the case of the latter plays an important role in the 1,5-dipolar cyclization of L(5). The spectral changes that originate from an intramolecular charge transfer (ICT) in the form of a pi(py)-->pi*(napy) transition can be tuned through acid/base-controlled switching for L(1)-L(3). A photoinduced isomerization for L(1)-L(3), 1, and 2 having flexible structures was observed under 365 nm light irradiation. Quantum chemical calculations revealed that the dinuclear complexes with structural asymmetry exhibit different metal-to-ligand charge-transfer transitions.


Subject(s)
Copper/chemistry , Naphthyridines/chemistry , Organometallic Compounds/chemistry , Organometallic Compounds/chemical synthesis , Photochemical Processes , Spectrum Analysis , Vinyl Compounds/chemistry , Crystallography, X-Ray , Hydrogen-Ion Concentration , Isomerism , Models, Molecular , Molecular Conformation , Quantum Theory
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