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1.
Adv Mater ; : e2401294, 2024 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-38547590

RESUMEN

Conventional security inks, generally directly printed on the data page surface, are vulnerable to counterfeiters, thereby raising the risk of chemical structural deciphering. In fact, polymer film-based data pages with customized patterns embedded within polymer matrix, rather than printed on the surface, emerge as a promising solution. Therefore, the key lies in developing fluorophores offering light dose-controlled fluorescent color inside polymer matrices. Though conventional fluorophores often suffer from photobleaching and uncontrolled photoreactions, disqualifying them for this purpose. Herein a diphenanthridinylfumaronitrile-based phototransformers (trans-D5) that undergoes photoisomerization and subsequent photocyclization during photopolymerization of the precursor, successively producing cis- and cyclo-D5 with stepwise redshifted solid-state emissions is developed. The resulting cyclo-D5 exhibits up to 172 nm emission redshift in rigidifying polymer matrices, while trans-D5 experiences a slightly blueshifted emission (≈28 nm), cis-D5 undergoes a modest redshift (≈14 nm). The markedly different rigidochromic behaviors of three D5 molecules within polymer matrices enable multicolor photochemical printing with a broad hue ranging from 38 to 10 via an anticlockwise direction in Munsell color space, yielding indecipherable fluorescent patterns in polymer films. This work provides a new method for document protection and implements advanced security features that are unattainable with conventional inks.

2.
J Inflamm Res ; 16: 1325-1342, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37006812

RESUMEN

Background: Chemokines have been reported to play an important role in cancer immunotherapy. This study aimed to explore the chemokines involved in lung cancer immunotherapy. Methods: All the public data were downloaded from The Cancer Genome Atlas Program database. Quantitative real time-PCR was used to detect the mRNA level of specific molecules and Western blot was used for the protein level. Other experiments used include luciferase reporter experiments, flow cytometric analysis, Chromatin immunoprecipitation assay, ELISA and co-cultured system. Results: We found that the CCL7, CCL11, CCL14, CCL24, CCL25, CCL26, CCL28 had a higher level, while the CCL17, CCL23 had a lower level in immunotherapy non-responders. Also, we found that immunotherapy non-responders had a higher level of CD56dim NK cells, NK cells, Th1 cells, Th2 cells and Treg, yet a lower level of iDC and Th17 cells. Biological enrichment analysis indicated that in the patients with high Treg infiltration, the pathways of pancreas beta cells, KRAS signaling, coagulation, WNT BETA catenin signaling, bile acid metabolism, interferon alpha response, hedgehog signaling, PI3K/AKT/mTOR signaling, apical surface, myogenesis were significantly enriched in. CCL7, CCL11, CCL26 and CCL28 were selected for further analysis. Compared with the patients with high CCL7, CCL11, CCL26 and CCL28 expression, the patients with low CCL7, CCL11, CCL26 and CCL28 expression had a better performance of immunotherapy response and this effect might partly be due to Treg cells. Furthermore, biological exploration and clinical correlation of CCL7, CCL11, CCL26 and CCL28 were conducted, Finally, CCL28 was selected for validation. Experiments showed that under the hypoxia condition, HIF-1α was upregulated, which can directly bind to the promoter region of CCL28 and lead to its higher level. Also, CCL28 secreted by lung cancer cells could induce Tregs infiltration. Conclusion: Our study provides a novel insight focused on the chemokines in lung cancer immunotherapy. Also, CCL28 was identified as an underlying biomarker for lung cancer immunotherapy.

3.
Acta Biomater ; 159: 201-210, 2023 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-36724862

RESUMEN

Composite MXene-based materials are prone to crack propagation, thus limiting their tensile properties. Numerous efforts have been devoted to removing material constraints and fabricating unitary MXene elastic films. Here, for the first time, inspired by the intestinal wrinkles and villi structure, we presented a ductile, biologically friendly, and highly conductive MXene-based microneedle (MMN) dressing composed of stacked MXene film and superfine microneedle arrays through a simple stretching and laser engraving strategy for wound healing. By utilizing photothermal responsive MXene, periodic porous structures, and a temperature-responsive polymer to construct the MMN dressing, the system can act as an effective route for facilitating controllable drug delivery controlled by near-infrared (NIR) irradiation. In addition, superior conductivity imparts them with the capacity to realize continuous and steady monitoring of motion sensing. The practical performance further demonstrated that the versatile MMN dressing showed obvious therapeutic efficacy in vivo animal wound models. Thus, it is believed that MMN dressings with biomimetic structures, controllable drug release, and conductive pathways will open a new chapter for wound management and widen other practical applications in biomedical fields, such as artificial tendons and soft robotics. STATEMENT OF SIGNIFICANCE: MXene-based materials have been demonstrated as critical tools in advancing our understanding of wound healing. However, the rapid crack propagation is a constraint on their tensile properties. Here, inspired by the intestinal wrinkles and villi structure, a single-step method has also been discussed to present a MXene-based microneedle dressing composed of unitary MXene elastic film and superfine microneedle arrays. At the same time, the dressing with biomimetic structures, controllable drug release, and conductive pathways has prospects in intelligent wound management and varieties of related biomedical fields.


Asunto(s)
Vendajes , Cicatrización de Heridas , Animales , Sistemas de Liberación de Medicamentos , Liberación de Fármacos
4.
Talanta ; 253: 123888, 2023 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-36087412

RESUMEN

Western blot (WB) is the most commonly used scheme for protein identification in life science, but it still faces great challenges in the accurate quantitative detection of low-abundance proteins. Here, we proposed a novel surface-enhanced Raman scattering-based Western blot (SERS-WB) to solve this challenge. SERS nanotags were used as quantitative labels of proteins, which were composed of gold-silver core-shell nanoparticles, and Nile blue A (NBA) molecules were anchored on the interface of the core and shell. The results show that the SERS-WB possessed excellent sensitivity with detection limit of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) protein of 0.15 pg, as well as wide linear dynamic range (LDR) of 382 fg to 382 ng. In addition, the target protein on nitrocellulose (NC) membrane could be directly identified by colorimetric signal due to the aggregation effect of nanoparticles, which greatly simplifies the procedure. This as-proposed strategy will bring new thoughts to technological innovation of WB.


Asunto(s)
Western Blotting
5.
Sci Adv ; 8(44): eadd1980, 2022 Nov 04.
Artículo en Inglés | MEDLINE | ID: mdl-36322650

RESUMEN

Using smart photochromic and luminescent tissues in camouflage/cloaking of natural creatures has inspired efforts to develop synthetic stimuli-responsive materials for data encryption and anticounterfeiting. Although many optical data-encryption materials have been reported, they generally require only one or a simple combination of few stimuli for decryptions and rarely offer output corruptibility that prevents trial-and-error attacks. Here, we report a series of multiresponsive donor-acceptor Stenhouse adducts (DASAs) with unprecedented switching behavior and controlled reversibility via diamine conformational locking and substrate free-volume engineering and their capability of sequential logic encryption (SLE). Being analogous to the digital circuits, the output of DASA gel-based data-encryption system depends not only on the present input stimulus but also on the sequence of past inputs. Incorrect inputs/sequences generate substantial fake information and lead attackers to the point of no return. This work offers new design concepts for advanced data-encryption materials that operate via SLE, paving the path toward advanced encryptions beyond digital circuit approaches.

6.
Am J Cancer Res ; 12(8): 3870-3891, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36119825

RESUMEN

Lung adenocarcinoma (LUAD) is a very heterogeneous cancer with a bad prognosis. Pyroptosis and ferroptosis are two newly discovered forms of regulated cell death, which can trigger inflammation-related immunosuppression in tumor microenvironments, thereby promoting tumor growth. So far, there has been no thorough systematic investigation of the predictive values of ferroptosis and pyroptosis-related genes in LUAD. Therefore, in this study, we conducted a combined analyses in the gene expression of ferroptosis and pyroptosis and identified four distinct subgroups: immobility, ferroptosis, pyroptosis, and mixed. The gene sets most closely associated to both ferroptosis and pyroptosis were utilized to build a risk prediction model based on their variations in survival and biological activities. More importantly, our conclusions from bioinformatics analyses were validated by external experiments in patients with LUAD. In conclusion, the establishment of LUAD subgroups based on the ferroptosis- and pyroptosis-related gene expression profile provided new insights into understanding the roles of programmed cell death in oncogenesis and might contribute to the development of individualized therapy.

7.
Cancer Gene Ther ; 29(12): 2001-2012, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-35948763

RESUMEN

The association between cancer-associated fibroblasts (CAFs) and tumor microenvironment (TME) is a key factor in promoting tumor progression. However, the correlation between CAFs and TME in breast carcinoma has not been elucidated. Thus, further study about the cross-effect between CAFs and TME can provide novel strategies for breast carcinoma treatment, particularly targeted immunotherapy. First, we systematically analyzed cell communication in a single-cell dataset and identified the interacted genes between CAFs and TME components. Then, a robust fibroblast-related score (FRS) model was developed using the LASSO algorithm. The FRS can be a reliable adverse prognostic factor in three cohorts with breast carcinoma. Functional enrichment analysis and single-sample Gene Set Enrichment Analysis showed that patients with a high FRS had cold tumors with active proliferation and immunosuppression. Patients with a low FRS presented with hot tumors with active immune and cell-killing functions. Genomic variation analysis revealed that patients with a low FRS had a higher somatic mutation load and copy number variation burden. Finally, patients with a low FRS were more sensitive to chemotherapy and immunotherapy, particularly anti-PD-1 therapy. In conclusion, a reliable FRS model was constructed not only reliable for predicting prognosis but also competent to estimate clinical immunotherapy and chemotherapy response for patients with BRCA, which might provide significant clinical implications for guiding clinical decision-making for patients with BRCA.


Asunto(s)
Neoplasias de la Mama , Fibroblastos Asociados al Cáncer , Humanos , Femenino , Variaciones en el Número de Copia de ADN , Pronóstico , Inmunoterapia , Neoplasias de la Mama/genética , Neoplasias de la Mama/terapia , Microambiente Tumoral/genética
8.
Cancer Sci ; 113(10): 3405-3416, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35879596

RESUMEN

Most breast cancer-related deaths are caused by metastasis in vital organs including the lungs. Development of supportive metastatic microenvironments, referred to as premetastatic niches (PMNs), in certain distant organs before arrival of metastatic cells, is critical in metastasis. However, the mechanisms of PMN formation are not fully clear. Here, we demonstrated that chemoattractant C-C motif chemokine ligand 2 (CCL2) could be stimulated by heat shock protein 60 (HSP60) on the surface of murine 4 T1 breast cancer cell-released LC3+ extracellular vesicles (LC3+ EVs) via the TLR2-MyD88-NF-κB signal cascade in lung fibroblasts, which subsequently promoted lung PMN formation through recruiting monocytes and suppressing T cell function. Consistently, reduction of LC3+ EV release or HSP60 level or neutralization of CCL2 markedly attenuated PMN formation and lung metastasis. Furthermore, the number of circulating LC3+ EVs and HSP60 level on LC3+ EVs in the plasma of breast cancer patients were positively correlated with disease progression and lung metastasis, which might have potential value as biomarkers of lung metastasis in breast cancer patients (AUC = 0.898, 0.694, respectively). These findings illuminate a novel mechanism of PMN formation and might provide therapeutic targets for anti-metastasis therapy for patients with breast cancer.


Asunto(s)
Neoplasias de la Mama , Vesículas Extracelulares , Neoplasias Pulmonares , Animales , Neoplasias de la Mama/patología , Chaperonina 60/metabolismo , Factores Quimiotácticos/metabolismo , Vesículas Extracelulares/metabolismo , Femenino , Humanos , Ligandos , Neoplasias Pulmonares/patología , Ratones , Proteínas Asociadas a Microtúbulos , Factor 88 de Diferenciación Mieloide/metabolismo , FN-kappa B/metabolismo , Metástasis de la Neoplasia/patología , Receptor Toll-Like 2 , Microambiente Tumoral
9.
RSC Adv ; 12(5): 2536, 2022 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-35427088

RESUMEN

[This corrects the article DOI: 10.1039/D0RA09106E.].

10.
Colloids Surf B Biointerfaces ; 214: 112460, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35298951

RESUMEN

The quantitative determination of trace free testosterone (FT) is of great significance for the diagnosis of androgen-related endocrine diseases. Herein, a fascinating detection protocol was developed for highly sensitive FT analysis through a competitive immunoassay mechanism, which was composed of magnetic nanobeads (MNBs) and gap-enhanced surface enhanced Raman scattering (SERS) nanotags. With the MNBs as detection carriers, trace FT could be enriched by simple magnetic separation. The SERS nanotag constructed with silver-gold core-shell nanoparticle was acted as quantitative label, and Raman indicators were located at the interface between silver core and gold shell. It is demonstrated that the as-proposed protocol achieves high detection sensitivity for FT of 12.11 fg mL-1, and wider linear dynamic detection range (LDR) in the concentration of 100 fg mL-1 to 100 ng mL-1 with R2 value of 0.979, which is due to the enhanced Raman signal of the gap-enhanced SERS nanotag and the high surface-to-volume ratio of the MNB, respectively. Taking advantages of such sensitivity and accuracy approach, the as-developed powerful strategy presents potential applications for rapid disease diagnosis through analyzing trace levels of FT, and can also provide guidance for the exploitation of analysis project of other analytes.


Asunto(s)
Nanopartículas del Metal , Plata , Oro , Fenómenos Magnéticos , Espectrometría Raman/métodos , Testosterona
11.
Front Genet ; 13: 813438, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35145551

RESUMEN

Acute myocardial infarction (AMI) is a leading cause of death and disability worldwide. Early diagnosis of AMI and interventional treatment can significantly reduce myocardial damage. However, owing to limitations in sensitivity and specificity, existing myocardial markers are not efficient for early identification of AMI. Transcriptome-wide association studies (TWASs) have shown excellent performance in identifying significant gene-trait associations and several cardiovascular diseases (CVDs). Furthermore, ferroptosis is a major driver of ischaemic injury in the heart. However, its specific regulatory mechanisms remain unclear. In this study, we screened three Gene Expression Omnibus (GEO) datasets of peripheral blood samples to assess the efficiency of ferroptosis-related genes (FRGs) for early diagnosis of AMI. To the best of our knowledge, for the first time, TWAS and mRNA expression data were integrated in this study to identify 11 FRGs specifically expressed in the peripheral blood of patients with AMI. Subsequently, using multiple machine learning algorithms, an optimal prediction model for AMI was constructed, which demonstrated satisfactory diagnostic efficiency in the training cohort (area under the curve (AUC) = 0.794) and two external validation cohorts (AUC = 0.745 and 0.711). Our study suggests that FRGs are involved in the progression of AMI, thus providing a new direction for early diagnosis, and offers potential molecular targets for optimal treatment of AMI.

12.
Talanta ; 237: 122955, 2022 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-34736680

RESUMEN

Ultrasensitive, multiplex, rapid, and accurate quantitative determination of trace antibiotics remains a challenging issue, which is of importance to public health and safety. Herein, we presented a multiplex strategy based on magnetic nanoparticles and surface-enhanced Raman scattering (SERS) nanotags for simultaneous detection of chloramphenicol (CAP) and tetracycline (TTC). In practice, SERS nanotags based on Raman reporter probes (RRPs) encoded gold-silver core-shell nanostars were used as detection labels for identifying different types of antibiotics, and the magnetic nanoparticles could be separated simply by magnetic force, which significantly improves the detection efficiency, reduces the analysis cost, and simplifies the operation. Our results demonstrate that the as-proposed assay possesses the capacities of high sensitivity and multiplexing with the limits of detection (LODs) for CAP and TTC of 159.49 and 294.12 fg mL-1, respectively, as well as good stability and reproducibility, and high selectivity and reliability. We believe that this strategy holds a great promising perspective for the detection of trace amounts of antibiotics in microsystems, which is crucial to our life. Additionally, the assay can also be used to detect other illegal additives by altering the appropriate antibodies or aptamers.


Asunto(s)
Nanopartículas de Magnetita , Nanopartículas del Metal , Antibacterianos , Oro , Reproducibilidad de los Resultados , Plata , Espectrometría Raman
13.
Electrophoresis ; 43(3): 464-471, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34611912

RESUMEN

We developed a low-cost polymer-film spiral inertial microfluidic device for the effective size-dependent separation of malignant tumor cells. The device was fabricated in polymer films by rapid laser cutting and chemical bonding. After fabricating the prototype device, the separation performance of our device was evaluated using particles and cells. The effects of operational flow rate, cell diameter, and cell concentration on the separation performance were explored. Our device successfully separated tumor cells from polydisperse white blood cells according to their different migration modes and lateral positions. Then, the separation of rare cells was carried out using the high-concentration lysed blood spiked with 200 tumor cells. Experimental results showed that 83.90% of the tumor cells could be recovered, while 99.87% of white blood cells could be removed. We successfully employed our device for processing clinical pleural effusion samples from patients with advanced metastatic breast cancer. Malignant tumor cells with an average purity of 2.37% could be effectively enriched, improving downstream diagnostic accuracy. Our device offers the advantages of label-free operation, low cost, and fast fabrication, thus being a potential tool for effective cell separation.


Asunto(s)
Técnicas Analíticas Microfluídicas , Neoplasias , Separación Celular , Humanos , Dispositivos Laboratorio en un Chip , Microfluídica , Polímeros
14.
Med Sci Monit ; 27: e932275, 2021 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-34719665

RESUMEN

BACKGROUND Immune-checkpoint inhibitors have propelled the field of therapeutics for small cell lung cancer (SCLC) treatment, but are only beneficial to some patients. The objective of this study was to identify valid biomarkers for good potential response to immunotherapy. MATERIAL AND METHODS We performed an integrated analysis of the available datasets from the Gene Expression Omnibus (GEO) projects, Cancer Cell Line Encyclopedia (CCLE), TISIDB database, and Lung Cancer Explorer (LCE) database. Six prognosis-related genes (MCM2, EZH2, CENPK, CHEK1, CDKN2A, and EXOSC2) were identified utilizing the meta workflow of data analysis methods. We performed subclass mapping to compare their expression profiles to other datasets of patients who responded to immunotherapy. A drug sensitivity predictive model was used to predict the chemotherapeutic response to cisplatin and etoposide. RESULTS Our results showed that the expression of the 6 key genes was significantly associated with the overall survival of patients with SCLC. Lower expression of these 6 genes was correlated to the response to anti-PD-1 treatment. Additionally, low expression of MCM2, EZH2, CENPK, and CHEK1 was correlated with increased sensitivity to cisplatin, but not etoposide. CONCLUSIONS Overall, our data showed that MCM2, EZH2, CENPK, CHEK1, CDKN2A, and EXOSC2 are potential prognostic and predictive biomarkers for response to immune-checkpoint inhibitor treatment in patients with SCLC. Further studies with large sample sizes are required to validate our findings and to explore the detailed mechanisms underlying the role of these genes in SCLC.


Asunto(s)
Biomarcadores de Tumor/genética , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inmunoterapia/métodos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Carcinoma Pulmonar de Células Pequeñas/genética , Biomarcadores de Tumor/inmunología , Estudios de Cohortes , Humanos , Inhibidores de Puntos de Control Inmunológico/inmunología , Neoplasias Pulmonares/inmunología , Pronóstico , Carcinoma Pulmonar de Células Pequeñas/inmunología , Resultado del Tratamiento
15.
PeerJ ; 9: e12140, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34616611

RESUMEN

BACKGROUND: Lung adenocarcinoma (LUAD) is the most common histologic subtype of lung cancer. Studies have found that miR-1293 is related to the survival of LUAD patients. Unfortunately, its role in LUAD remains not fully clarified. METHODS: miR-1293 expression and its association with LUAD patients' clinical characteristics were analyzed in TCGA database. Also, miR-1293 expression was detected in LUAD cell lines. Cell viability, migration, invasion and expression of MMP2 and MMP9 were measured in LUAD cells following transfection with miR-1293 mimic or antagomir. Phosphoglucomutase (PGM) 5 was identified to be negatively related to miR-1293 in LUAD patients in TCGA database, and their association was predicated by Targetscan software. Hence, we further verified the relationship between miR-1293 and PGM5. Additionally, the effect and mechanism of miR-1293 were validated in a xenograft mouse model. RESULTS: We found miR-1293 expression was elevated, but PGM5 was decreased, in LUAD patients and cell lines. Higher miR-1293 expression was positively related to LUAD patients' pathologic stage and poor overall survival. miR-1293 mimic significantly promoted, whereas miR-1293 antagomir suppressed the viability, migration, invasion, and expression of MMP2 and MMP9 in LUAD cells. PGM5 was a target of miR-1293. Overexpression of PGM5 abrogated the effects of miR-1293 on the malignant phenotypes of LUAD cells. Administration of miR-1293 antagomir reduced tumor volume and staining of Ki-67 and MMP9, but elevated PGM5 expression in vivo. CONCLUSIONS: miR-1293 promoted the proliferation, migration and invasion of LUAD cells via targeting PGM5, which indicated that miR-1293 might serve as a potential therapeutic target for LUAD patients.

16.
RSC Adv ; 11(11): 6367-6373, 2021 02 02.
Artículo en Inglés | MEDLINE | ID: mdl-35423140

RESUMEN

Wound healing is a ubiquitous healthcare problem in clinical wound management. In this paper, the fabrication of a graphene hybrid supramolecular hydrogel (GS hydrogel) for wound dressing applications is demonstrated. The hydrogel is composed of two components, including N-acryloyl glycinamide (NAGA) as the scaffold and graphene as the photothermally responsive active site for photothermal therapy. Based on the multiple hydrogen bonds between the dual amide motifs in the side chain of N-acryloyl glycinamide, the hydrogel exhibits high tensile strength (≈1.7 MPa), good stretchability (≈400%) and self-recoverability. In addition, the GS hydrogel shows excellent antibacterial activity towards methicillin-resistant Staphylococcus aureus (MRSA), benefiting from the addition of graphene that possesses great photothermal transition activity (≈85%). Significantly, in vivo animal experiments also demonstrated that the GS hydrogel effectively accelerates the wound healing processes by eradicating microbes, promoting collagen deposition and angiogenesis. In summary, this GS hydrogel demonstrates excellent mechanical performance, photothermal antimicrobial activity, and promotes skin tissue regeneration, and so has great application potential as a promising wound dressing material in clinical use.

17.
Exp Ther Med ; 20(1): 662-670, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32550888

RESUMEN

Pancreatic cancer is a common cause of worldwide cancer-related mortality with a poor 5-year survival rate. Aldehyde dehydrogenase (ALDH) activity is a possible marker for malignant stem cells in solid organ systems, including the pancreas, and N,N-diethylaminobenzaldehyde (DEAB) is able to inhibit ALDH activity. In the present study, the role of DEAB in the treatment of pancreatic cancer cells and the potential underlying mechanisms were investigated. The ALDH activities of pancreatic cancer cell lines treated with or without DEAB were analyzed by an ALDEFLUOR™ assay. The Cell Counting Kit-8 and colony formation assays, and cell cycle analysis were used to evaluate the viability, colony-forming ability and cell quiescence of cell lines under DEAB treatment, respectively. DEAB and/or gemcitabine-induced cell apoptosis was assessed by flow cytometry. DEAB reduced ALDH activity and inhibited the proliferation, colony-forming ability and cell quiescence of pancreatic cancer cell lines. Compared with respective controls, DEAB alone and the combination of gemcitabine and DEAB significantly decreased cell viability and increased cell apoptosis. Moreover, reverse transcription-PCR and western blotting were used to measure the expressions of B cell lymphoma 2 (Bcl2) associated X protein (Bax) and Bcl2 mRNA and protein. The anti-cancer effect of DEAB was associated with upregulation of Bax expression. Therefore, targeting ALDH with DEAB may be a potential therapeutic choice for pancreatic cancer, demonstrating a synergic effect with gemcitabine.

18.
Nanomedicine (Lond) ; 13(3): 297-311, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-29338562

RESUMEN

AIM: Severe cardiac toxicity of doxorubicin and an immunosuppressive tumor micro-environment become main obstacles for the effective treatment of B-cell lymphoma. In this research, rituximab-conjugated and doxorubicin-loaded microbubbles (RDMs) were designed for exploring a combination approach of targeted microbubbles with ultrasound (US) irradiation and PD-1 inhibitor to overcome obstacles mentioned above. METHODS: In vivo studies were performed on SU-DHL-4 cell-grafted mice and ex vivo studies were performed on CD20+ human SU-DHL-4 cells and human T cells. RESULTS: A greater therapeutic effect and higher expression of PD-L1 protein expression were obtained with RDMs with US irradiation in vivo. A significant inhibitory effect on SU-DHL-4 B-cell lymphoma cells was observed after treated by RDMs with US irradiation and PD-1 inhibitor ex vivo. CONCLUSION: Combination of RDMs with US irradiation and PD-1 inhibitor could be a promising therapeutic strategy for B-cell lymphoma.


Asunto(s)
Antígeno B7-H1/inmunología , Linfoma de Células B/tratamiento farmacológico , Receptor de Muerte Celular Programada 1/inmunología , Linfocitos T/inmunología , Animales , Línea Celular Tumoral , Doxorrubicina/administración & dosificación , Doxorrubicina/química , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/inmunología , Humanos , Linfoma de Células B/inmunología , Linfoma de Células B/patología , Ratones , Microburbujas/uso terapéutico , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Rituximab/administración & dosificación , Rituximab/química , Linfocitos T/efectos de los fármacos , Linfocitos T/efectos de la radiación , Ondas Ultrasónicas , Ensayos Antitumor por Modelo de Xenoinjerto
19.
J Exp Clin Cancer Res ; 36(1): 24, 2017 02 06.
Artículo en Inglés | MEDLINE | ID: mdl-28166836

RESUMEN

BACKGROUND: One of the main problems in B cell lymphoma treatment is severe adverse effects and low therapeutic efficacy resulting from systemic chemotherapy. A pH-sensitive controlled drug release system based on mesoporous silica nanoparticles was constructed for targeted drug delivery to tumor cells to reduce systemic toxicity and improve the therapeutic efficacy. METHODS: In this study, the doxorubicin (DOX) was filled into the mesopores of the functional MSNs (DMSNs). Furthermore, rituximab was introduced as the targeted motif of functional DMSNs using an avidin-biotin bridging method to evaluate the targetability to tumor cells. Then, the cell viability and apoptosis efficiency after treatment with rituximab-conjugated DMSNs (RDMSNs) were estimated by using CCK-8 assay and flow cytometry, respectively. Additionally, the research in vivo was performed to evaluate the enhanced antitumor efficacy and the minimal toxic side effects of RDMSNs. Also, TUNEL staining assay was employed to explore the mechanism of antitumor effects of RDMSNs. RESULTS: This targeted drug delivery system exhibited low premature drug release at a physiological pH and efficient pH-responsive intracellular release under weakly acidic conditions. The in vitro tests confirmed that targeted RDMSNs could selectively adhere to the surface of lymphoma B cells via specific binding with the CD20 antigen and be internalized into CD20 positive Raji cells but few CD20 negative Jurkat cells, which leads to increased cytotoxicity and apoptosis of the DOX in Raji cells due to the release of the entrapped DOX with high efficiency in the slightly acidic intracellular microenvironment. Furthermore, the in vivo investigations confirmed that RDMSNs could efficiently deliver DOX to lymphoma B cells by pH stimuli, thus inducing cell apoptosis and inhibiting tumor growth, while with minimal toxic side effects. CONCLUSIONS: This targeted and pH-sensitive controlled drug delivery system has the potential for promising application to enhance the therapeutic index and reduce the side effects of B cell lymphoma therapy.


Asunto(s)
Antineoplásicos/administración & dosificación , Doxorrubicina/administración & dosificación , Linfoma de Células B/tratamiento farmacológico , Nanopartículas/química , Rituximab/administración & dosificación , Dióxido de Silicio/química , Animales , Antineoplásicos/química , Antineoplásicos/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/química , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Doxorrubicina/química , Doxorrubicina/farmacología , Humanos , Concentración de Iones de Hidrógeno , Células Jurkat , Ratones , Rituximab/química , Rituximab/farmacología , Resultado del Tratamiento , Ensayos Antitumor por Modelo de Xenoinjerto
20.
Analyst ; 141(24): 6549-6556, 2016 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-27833950

RESUMEN

For multiplex bioassays, one effective strategy is to employ microfluidic chips based on an array of photonic crystal beads (PCBs) that are encoded by their characteristic reflection spectrum (CRS). In this paper, we report a hyperspectral imaging system and algorithms for the high throughput decoding of a PCB array and subsequent detection. The results showed that the decoding accuracy of up to ∼500 PCBs is 98.56% with an excellent ability to extract low-intensity fluorescence intensities. The results also demonstrated hyperspectral imaging techniques which can simultaneously obtain both spatial and spectral information as powerful tools in the analysis of multiplex bioassays or microfluidic chips.


Asunto(s)
Bioensayo , Análisis Espectral , Luz , Microfluídica , Fotones
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