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1.
Front Comput Neurosci ; 18: 1387004, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38694950

RESUMO

Introduction: The blood oxygen level-dependent (BOLD) signal derived from functional neuroimaging is commonly used in brain network analysis and dementia diagnosis. Missing the BOLD signal may lead to bad performance and misinterpretation of findings when analyzing neurological disease. Few studies have focused on the restoration of brain functional time-series data. Methods: In this paper, a novel U-shaped convolutional transformer GAN (UCT-GAN) model is proposed to restore the missing brain functional time-series data. The proposed model leverages the power of generative adversarial networks (GANs) while incorporating a U-shaped architecture to effectively capture hierarchical features in the restoration process. Besides, the multi-level temporal-correlated attention and the convolutional sampling in the transformer-based generator are devised to capture the global and local temporal features for the missing time series and associate their long-range relationship with the other brain regions. Furthermore, by introducing multi-resolution consistency loss, the proposed model can promote the learning of diverse temporal patterns and maintain consistency across different temporal resolutions, thus effectively restoring complex brain functional dynamics. Results: We theoretically tested our model on the public Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset, and our experiments demonstrate that the proposed model outperforms existing methods in terms of both quantitative metrics and qualitative assessments. The model's ability to preserve the underlying topological structure of the brain functional networks during restoration is a particularly notable achievement. Conclusion: Overall, the proposed model offers a promising solution for restoring brain functional time-series and contributes to the advancement of neuroscience research by providing enhanced tools for disease analysis and interpretation.

3.
Adv Sci (Weinh) ; 10(20): e2300339, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37148168

RESUMO

Infectious diabetic ulcers (IDU) require anti-infection, angiogenesis, and nerve regeneration therapy; however, the latter has received comparatively less research attention than the former two. In particular, there have been few reports on the recovery of mechanical nociception. In this study, a photothermal controlled-release immunomodulatory hydrogel nanoplatform is tailored for the treatment of IDU. Due to a thermal-sensitive interaction between polydopamine-reduced graphene oxide (pGO) and the antibiotic mupirocin, excellent antibacterial efficacy is achieved through customized release kinetics. In addition, Trem2+ macrophages recruited by pGO regulate collagen remodeling and restore skin adnexal structures to alter the fate of scar formation, promote angiogenesis, accompanied by the regeneration of neural networks, which ensures the recovery of mechanical nociception and may prevent the recurrence of IDU at the source. In all, a full-stage strategy from antibacterial, immune regulation, angiogenesis, and neurogenesis to the recovery of mechanical nociception, an indispensable neural function of skin, is introduced to IDU treatment, which opens up an effective and comprehensive therapy for refractory IDU.


Assuntos
Diabetes Mellitus , Nociceptividade , Humanos , Preparações de Ação Retardada , Úlcera , Antibacterianos
4.
Artigo em Inglês | MEDLINE | ID: mdl-36847900

RESUMO

PURPOSE: Left bundle branch pacing (LBBP) is as an innovative physiological pacing approach. The research on LBBP in non-obstructive hypertrophic cardiomyopathy (NOHCM) patients is scarce. This study aimed to assess the feasibility, safety, and effect of LBBP in bradycardia NOHCM patients with permanent pacemaker (PPM) implantation indication. METHODS: Thirteen consecutive patients with NOHCM who received LBBP were retrospectively enrolled as a hypertrophic cardiomyopathy (HCM) group. Following 1:3 matching, 39 patients without HCM were randomly matched as a control group. Echocardiographic index and pacing parameters were collected. RESULTS: The successful LBBP was achieved in 96.2% of all cases (50/52), and the success rate of the HCM group was 92.3% (12/13). In the HCM group, the paced QRS duration (from the pacing stimulus to QRS end) was 145.6±20.8 ms. The stimulus to left ventricular activation time (s-LVAT) was 87.4±15.2 ms. In the control group, the paced QRS duration was 139.4±17.2 ms, and the s-LVAT was 79.9±14.1 ms. During the implantation, R-wave sensing and the pacing threshold of the HCM group were significantly higher than the control group (20.2±10.5 vs 12.5±5.9 mV, P < 0.05; 0.8±0.3 vs 0.6±0.2V/0.4 ms, P < 0.05). In addition, the fluoroscopic duration and procedural duration were longer in the HCM group (14.8±8.3 vs 10.3±6.6min, P = 0.07; 131.8±50.5 vs 101.4±41.6 min, P < 0.05). The lead insertion depth was 15±2 mm in the HCM group, and no procedure-related complications occurred. During the 12-month follow-up, pacing parameters remained stable and were of no significance in the two groups. The cardiac function did not deteriorate, and the left ventricular outflow tract gradient (LVOTG) did not increase in the follow-up. CONCLUSION: LBBP might be feasible and safe for NOHCM patients with conventional bradycardia pacing indication, and there is no deterioration in cardiac function and LVOTG of patients with NOHCM.

6.
PLoS Pathog ; 19(1): e1011096, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36693067

RESUMO

Fusobacterium nucleatum (Fn) is a critical colorectal cancer (CRC)-associated bacterium. DNA hunger/stationary phase protective proteins (Dps) are bacterial ferritins that protect DNA from oxidative stress. However, little is known about the regulatory roles of Fn-Dps towards host cellular functions. Here, we identified Fn-Dps from the culture supernatant of Fn by mass spectrometry, and prepared the recombinant of Fn-Dps protein. We show a novel virulence protein of Fn, Fn-Dps, which lyses and disrupts erythrocytes by the competition for iron acquisition. Also, Fn-Dps facilitates intracellular survival of Fn in macrophages by upregulating the expression of the chemokine CCL2/CCL7. In addition, Fn-Dps can elicit a strong humoral immune response, and mucosal immunization with Fn-Dps conferred protection against Fn in the intestinal tract. Moreover, a high level of anti-Fn-Dps antibody was prevalent in populations, and elevated anti-Fn-Dps antibody levels were observed in CRC patients. Furthermore, Fn-Dps promotes the migration of CRC cells via the CCL2/CCL7-induced epithelial-mesenchymal transition (EMT) and promotes CRC metastasis in vivo.


Assuntos
Neoplasias Colorretais , Fusobacterium nucleatum , Humanos , Fusobacterium nucleatum/genética , Fatores de Virulência/genética , Intestinos/patologia , Eritrócitos/metabolismo
7.
Nat Commun ; 14(1): 21, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36596763

RESUMO

Self-assembled systems have recently attracted extensive attention because they can display a wide range of phase morphologies in nanocomposites, providing a new arena to explore novel phenomena. Among these morphologies, a bicontinuous structure is highly desirable based on its high interface-to-volume ratio and 3D interconnectivity. A bicontinuous nickel oxide (NiO) and tin dioxide (SnO2) heteroepitaxial nanocomposite is revealed here. By controlling their concentration, we fabricated tuneable self-assembled nanostructures from pillars to bicontinuous structures, as evidenced by TEM-energy-dispersive X-ray spectroscopy with a tortuous compositional distribution. The experimentally observed growth modes are consistent with predictions by first-principles calculations. Phase-field simulations are performed to understand 3D microstructure formation and extract key thermodynamic parameters for predicting microstructure morphologies in SnO2:NiO nanocomposites of other concentrations. Furthermore, we demonstrate significantly enhanced photovoltaic properties in a bicontinuous SnO2:NiO nanocomposite macroscopically and microscopically. This research shows a pathway to developing innovative solar cell and photodetector devices based on self-assembled oxides.

8.
Front Nutr ; 9: 999995, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36263299

RESUMO

Background: Lipid metabolism disorders contribute to the risk factor of prostatic hyperplasia. Lipid ratios have also attracted a lot of attention. Yet, research about the correlation of lipid ratios with prostatic hyperplasia is limited. Hence, the aim of this study was to investigate the association of lipid ratios with the risk of benign prostatic hyperplasia (BPH) in Chinese male subjects. Methods: Healthy men who underwent routine health check-ups from January 2017 to December 2019 were recruited. Twenty-four thousand nine hundred sixty-two individuals were finally enrolled in this research. Binary logistic regression analysis was performed to investigate the relationship between lipid ratios and BPH in Chinese adults. Results: After health examinations for more than 2 years, 18.46% of subjects were ascertained as incident BPH cases. Higher age, body mass index (BMI), prostate-specific antigen (PSA), triglycerides (TGs), low-density lipoprotein cholesterol (LDL-C), triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, total cholesterol to high-density lipoprotein cholesterol (TC/HDL-C) ratio, and lower high-density lipoprotein cholesterol (HDL-C) were significantly associated with BPH risk, while total cholesterol (TC) was not significant. When quartiles of TG/HDL-C and TC/HDL-C were analyzed in multivariable model, higher TG/HDL-C and TC/HDL-C were associated with a risk of BPH (odds ratio [OR] = 2.11; 95% confidence interval [CI]: 1.89, 2.36; P-trend < 0.001; and OR = 1.67; 95% CI: 1.50, 1.85; P-trend < 0.001, respectively). In addition, stratified analyses based on the general population exhibited that with increasing age (≥35 years) the relationship of TG/HDL-C ratio with BPH risk was dominantly positive (all P-trend < 0.001, P-interaction = 0.001), and significant associations were also found in blood pressure strata and FBG strata (all P-trend < 0.001), except men with BMI ≥ 28 kg/m2 were slightly weakened (OR = 2.01, 95% CI: 1.41, 2.85; P-trend = 0.04). Moreover, there were significant associations between quartiles of TC/HDL-C and the risk of BPH was observed mainly in age 55-64 years, BMI 18.5-23.9 Kg/m2, blood pressure strata, and FBG strata. However, the P-value for a linear trend among those with BMI ≥ 28 Kg/m2 in which participants at the highest quartile of TC/HDL-C had an OR of 1.45 (95% CI: 1.09, 1.93) was 0.594. Additionally, higher TG/HDL-C ratio (≥0.65) may be a risk factor for BPH in China adults of different age decades (≥35 years) with normal TG and HDL-C. Conclusions: TG/HDL-C and TC/HDL-C were associated with BPH risk, TG/HDL-C was a powerful independent risk factor for BPH in Chinese adults, and higher TG/HDL-C ratio should be valued in male subjects with normal TG and HDL-C levels.

9.
Adv Healthc Mater ; 11(20): e2201596, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35920510

RESUMO

Myelin sheath reconstruction plays an important role in peripheral nerve regeneration. But the hindered reconstruction of myelin sheath, due to the inadequate repair phenotypes of macrophages and Schwann cells after peripheral nerve injury, often causes poor functional nerve recovery. Here, biomechanically-adapted immunohydrogels are prepared as the FK506-loaded platforms and nerve tissue engineering scaffolds to reconstruct myelin sheath for peripheral nerve regeneration. By immunofluorescent staining, an increase in the proportion of F4/80+ markers reveals that the biomechanically-adapted scaffolds facilitate recruitment of macrophages. Furthermore, the high Interleukin 10 (IL-10) mRNA expression level suggests the anti-inflammation learning effects of FK506 in vitro, which is further confirmed by a high CD206/TNF-α ratio in the FK506 Gel group in vivo. The immune learning effects are positively related to the increase in compactness and thickness of myelin sheath, indicating the synergy of structural reconstruction of myelin sheath and M2 phenotype polarization of macrophages. All these data indicate that the biomechanically-adapted immunohydrogels enhance recruitment of macrophages, educate M2 polarization of macrophages and promote a neuroprotective environment, which in consequence reconstructs myelin sheath for peripheral nerve regeneration.


Assuntos
Interleucina-10 , Bainha de Mielina , Bainha de Mielina/metabolismo , Interleucina-10/metabolismo , Tacrolimo/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Regeneração Nervosa/fisiologia , Células de Schwann/metabolismo , RNA Mensageiro/metabolismo
10.
ACS Biomater Sci Eng ; 8(8): 3424-3437, 2022 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-35878006

RESUMO

Novel copolymer brushes of quaternized sodium alginate-g-(2-ethyl-2-oxazoline)n are achieved by the grafting reaction of 2-ethyl-2-oxazoline (EOX) from benzyl bromide groups in quaternized sodium alginate (QSA). The average number of (EOX)n structural units is mediated from 1 to 5 by changing the molar ratio of the EOX monomer to benzyl bromide side groups. There exists obvious microphase separation between the QSA backbone and (EOX)n segments in the copolymer brushes due to their thermodynamic incompatibility. The strong hydrogen-bonding interaction between -OH groups in the backbone and N─C═O groups in (EOX)n segments is helpful for the construction of reversible supramolecular networks. The copolymer brushes show low cytotoxicity for HeLa cells and good antibacterial properties for Escherichia coli and Staphylococcus aureus for the contribution of hydrophilic (EOX)n segments and antibacterial activity of the quaternary ammonium. The antiprotein behavior of polymer surfaces is improved after rearrangement of (EOX)n segments by tetrahydrofuran (THF) vapor induction. These copolymer brushes have good prospects for biomedical applications.


Assuntos
Alginatos , Polímeros , Alginatos/farmacologia , Antibacterianos/química , Antibacterianos/farmacologia , Escherichia coli , Células HeLa , Humanos , Ligação de Hidrogênio , Polímeros/farmacologia
11.
Front Cardiovasc Med ; 9: 838708, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35369330

RESUMO

Aims: The present study aimed to compare the effects of left bundle branch area pacing (LBBAP) on cardiac function and clinical outcomes in patients with left bundle branch block (LBBB) and left ventricular ejection fraction (LVEF) >35 vs. ≤35%. Methods and Results: Thirty-six consecutive patients with LBBB and LVEF <50% were enrolled. All patients were followed up for a mean of 6 months. The successful LBBAP was defined as a paced QRS complex presented as right bundle branch block (RBBB) morphology and QRSd < 130 ms. Echocardiography parameters, pacing parameters and clinical outcomes were collected. The successful LBBAP was achieved in 77.8% of all cases (28/36). In LVEF > 35% group (70 ± 8 years, 9 male), the success rate was 81.0% (17/21). QRSd significantly decreased from 174 ± 23 ms to 108 ± 13 ms (P < 0.001). The pacing threshold and R-wave amplitude were 0.6 ± 0.2 V @ 0.5 ms and 12 ± 7 mV, respectively. In LVEF ≤ 35% group (69 ± 5 years, 9 male), the success rate was 73.3% (11/15) with QRSd decreasing from 188 ± 25 ms to 107 ± 11 ms (P < 0.001). The hyperresponders to LBBAP (functional recovery and LVEF ≥ 50%) in LVEF > 35% group was 52.9%, which were almost twice of that in LVEF ≤ 35% group (33.3%). Whether patients had LBBAP or left ventricular septal pacing (LVSP), patients in the LVEF > 35% group showed significantly lower incidence of heart failure hospitalizations or death from any cause (hazard ratio in LVEF > 35% group, 0.22; 95%CI, 0.06 to 0.75, P = 0.011). Conclusions: LBBAP can significantly shorten the QRSd and improve cardiac function in LBBB patients with either LVEF > 35 or ≤ 35%. LBBAP should be considered as an effective therapy for preventing the deterioration of cardiac function in early-stage heart failure patients with LBBB and LVEF > 35%.

12.
Cancer Treat Res Commun ; 28: 100379, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33951555

RESUMO

PD-1 immune checkpoint blockade and cytokine IL-33 have shown significant therapeutic effects in tumor immunotherapy. These therapies promote CD8+ T cell activation, proliferation, and effector functions. However, there were few research about the combined therapy efficacy. In this study, we established B16-empty vector and B16-IL33 melanoma mouse models and treated with PD-1 monoclonal antibody. We reported that PD-1 blockade combined with cytokine IL-33 further inhibited tumor progression and prolonged the survival of tumor-bearing mice. Mechanistically, the combination therapy was found to further facilitate CD4+ and CD8+ T lymphocytes accumulation, and enhance the antitumor effects of CD4+or CD8+tumor-infiltrating lymphocytes by promoting type-1 immune response within the tumor microenvironment using flow cytometry and quantitative real time polymerase chain reaction. Thus, PD-1 blockade combined with IL-33 has application potential in tumor immunotherapy. Further, this study provides a new promising strategy and theoretical basis for tumor combination immunotherapy.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Inibidores de Checkpoint Imunológico/uso terapêutico , Interleucina-33/uso terapêutico , Melanoma Experimental/tratamento farmacológico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Neoplasias Cutâneas/tratamento farmacológico , Animais , Anticorpos Monoclonais Humanizados/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Linhagem Celular Tumoral , Sinergismo Farmacológico , Feminino , Inibidores de Checkpoint Imunológico/farmacologia , Imunoterapia , Interleucina-33/farmacologia , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Linfócitos do Interstício Tumoral/imunologia , Melanoma Experimental/imunologia , Melanoma Experimental/patologia , Camundongos Transgênicos , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/patologia , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia
13.
Mater Sci Eng C Mater Biol Appl ; 123: 111998, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33812618

RESUMO

The novel amphiphilic acylated dextran-g-polytetrahydrofuran (AcyDex-g-PTHF) graft copolymers have been successfully synthesized via combination of living cationic ring-opening polymerization of tetrahydrofuran (THF) to prepare living PTHF chains with different molecular weights (Mn, PTHF) of 800-2800 g/mol with nucleophile substitution to mediate grafting numbers (GN) of 4-25 per 1000 Dex monosaccharide. The microphase separation in the graft copolymer exists for the incompatibility of hard dextran backbone and soft PTHF branches and the confined crystallization of backbone. This copolymer behaves excellent hemocompatibility with red blood cells, good biocompatibility with HeLa cells and strong resistance to bovine serum albumin adsorption. The microspheres (~1 µm) of graft copolymers loaded with drug ibuprofen exhibit pH sensitive controlled drug release behavior. Moreover, the AcyDex-g-PTHF/Ag nanocomposites show good antibacterial property against E. coli and S. aureus. This novel hemocompatible, biocompatible and antifouling AcyDex-g-PTHF graft copolymer will have potential application in biological and medical fields.


Assuntos
Nanopartículas Metálicas , Prata , Butileno Glicóis , Dextranos , Escherichia coli , Células HeLa , Humanos , Polímeros , Staphylococcus aureus
14.
Front Cell Dev Biol ; 9: 640224, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33553191

RESUMO

Sustaining efficacious T cell-mediated antitumor immune responses in the tumor tissues is the key to the success of cancer immunotherapy. Current strategies leverage altering the signals T cells sense in the tumor microenvironment (TME). Checkpoint inhibitor-based approaches block inhibitory signals such as PD-1 whereas cytokine-based therapies increase the level of immune-stimulatory cytokines such as IL-2. Besides extrinsic signals, the genetic circuit within T cells also participates in determining the nature and trajectory of antitumor immune responses. Here, we showed that efficacy of the IL33-based tumor immunotherapy was greatly enhanced in mice with T cell-specific Eomes deficiency. Mechanistically, we demonstrated that Eomes deficient mice had diminished proportions of exhausted/dysfunctional CD8+ T cells but increased percentages of tissue resident and stem-like CD8+ T cells in the TME. In addition, the IFNγ+TCF1+ CD8+ T cell subset was markedly increased in the Eomes deficient mice. We further demonstrated that Eomes bound directly to the transcription regulatory regions of exhaustion and tissue residency genes. In contrast to its role in inhibiting T cell immune responses at the tumor site, Eomes promoted generation of central memory T cells in the peripheral lymphoid system and memory recall responses against tumor growth at a distal tissue site. Finally, we showed that Eomes deficiency in T cells also resulted in increased efficacy of PD-1-blockade tumor immunotherapy. In all, our study indicates that Eomes plays a critical role in restricting prolonged T cell-mediated antitumor immune responses in the TME whereas promoting adaptive immunity in peripheral lymphoid organs.

15.
Carbohydr Polym ; 219: 201-209, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31151517

RESUMO

Sodium alginate (SA) is a marine-derived biocompatible polysaccharide with huge reserves and polyisobutylene (PIB) is a saturated elastomer with gas barrier property, bio-inertness, and biocompatibility. Herein, we developed the biomass-based ASA-g-(THF5-b-PIB) graft copolymer/Ag (3-11 nm, 0.7-3.8%) nanocomposites formed in-situ via combination of transition of terminal groups in PIB chains with grafting-onto method. The above graft copolymers exhibit microphase separation by self-assembly for the difference in chemical structure from backbone and branches and annealing process as well. The crystallization morphology from backbone depends on the Mn,PIB and GN, changing from thin strip to rod-like crystal. The pH sensitivity happens in drug release behavior of ASA-g-(THF5-b-PIB) micelles, which reach 100% of drug-release within 40 h at pH = 7.4. The ASA-g-(THF5-b-PIB)/Ag composites behave good antibacterial properties to both E. coli and S. aureus and anti-protein adsorption performance. This novel graft copolymer with comprehensive properties and would have a prospect in biomedical field.

16.
Clin Chem ; 64(9): 1327-1337, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29914865

RESUMO

BACKGROUND: Gut microbial dysbiosis contributes to the development of colorectal cancer (CRC). We evaluated the utility of fecal bacterial biomarker candidates identified by our 16S rDNA sequencing analysis for CRC diagnosis. METHODS: We measured the relative abundance of Fusobacterium nucleatum (Fn), Faecalibacterium prausnitzii (Fp), Bifidobacterium (Bb), and Lactobacillus (Lb) by quantitative PCR in fecal samples from 2 cohorts of 903 individuals. We evaluated and validated the diagnostic performance of these microbial ratios and investigated the antagonistic effect of Fn against 3 different indicator stains. RESULTS: The microbial ratio of Fn to Bb (Fn/Bb) had a superior sensitivity of 84.6% and specificity of 92.3% in detecting CRC (area under the curve, AUC = 0.911). The combination of Fn/Bb and Fn/Fp improved the diagnostic value (AUC = 0.943). Moreover, the combination of Fn/Bb and Fn/Fp offered 60.0% specificity and 90.0% sensitivity in detecting stage I of CRC (AUC = 0.804). In particular, Fn was negatively correlated with Fp in the CRC group. The performance for CRC diagnosis was confirmed in the validation cohort II. The culture supernatant from Fn exhibited strong bactericidal activity against probiotics Fp and Bb strains. CONCLUSIONS: This study found that Fn could play a role in microbiota dysbiosis via the secreted antagonistic substances against probiotics. Moreover, the ratio of Fn to the important probiotics Fp and Bb was identified as a valuable biomarker for screening early CRC.


Assuntos
Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/microbiologia , Fezes/microbiologia , Fusobacterium nucleatum/isolamento & purificação , Probióticos/isolamento & purificação , Biomarcadores/análise , DNA Ribossômico/genética , Fusobacterium nucleatum/genética , Microbioma Gastrointestinal , Humanos , Reação em Cadeia da Polimerase/métodos , RNA Ribossômico 16S/genética
17.
Cell Death Dis ; 9(3): 355, 2018 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-29500439

RESUMO

Fusobacterium nucleatum (Fn) is a tumor-associated obligate anaerobic bacterium, which has a role in the progression of colorectal cancer (CRC). Fn can invade and promote colon epithelial cells proliferation. However, how Fn survives and proliferates in its host cells remains largely unknown. In this study, we aimed to determine the molecular mechanisms underlying the morphology, survival, and proliferation of Fn in THP-1-derived macrophages (dTHP1). For the first time, we found that Fn is a facultative intracellular bacterium that can survive and limited proliferate in dTHP1 cells up to 72 h, and a live Fn infection can inhibit apoptosis of dTHP1 cells by activating the PI3K and ERK pathways. Both Fn bacteria and dTHP1 cells exhibit obvious morphological changes during infection. In addition, Infection of Fn-induced indoleamine 2,3-dioxygenase (IDO) expression by TNF-α-dependent and LPS-dependent pathway in a time-dependent and dose-dependent manner, and the IDO-induced low tryptophan and high kynurenine environment inhibited the intracellular multiplication of Fn in dTHP1 cells. IDO expression further impaired the function of peripheral blood lymphocytes, permitting the escape of Fn-infected macrophages from cell death. IDO inhibition abrogated this effect caused by Fn and relieved immune suppression. In conclusion, we identified IDO as an important player mediating intracellular Fn proliferation in macrophages, and inhibition of IDO may aggravate infection in Fn-associated tumor immunotherapy.


Assuntos
Infecções por Fusobacterium/enzimologia , Infecções por Fusobacterium/microbiologia , Fusobacterium nucleatum/fisiologia , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Macrófagos/microbiologia , Apoptose , Proliferação de Células/fisiologia , Sobrevivência Celular/fisiologia , Humanos , Interferon gama/metabolismo , Interleucina-6/metabolismo , Cinurenina/metabolismo , Linfócitos/microbiologia , Sistema de Sinalização das MAP Quinases , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Células THP-1 , Triptofano/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
18.
Biosens Bioelectron ; 102: 204-210, 2018 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-29145073

RESUMO

Tumor-derived exosomes (TEXs) are extracellular vesicles that are continuously released into the blood by tumor cells and carry specific surface markers of the original tumor cells. Substantial evidence has implicated TEXs as attractive diagnostic markers for cancer. However, the detection of TEXs in blood at an early tumor stage is challenging due to their very low concentration. Here, we established a method called PLA-RPA-TMA assay that allows TEXs to be detected with high sensitivity and specificity. Based on two proximity ligation assay (PLA) probes that recognize a biomarker on a TEX, we generated a unique surrogate DNA signal for the specific biomarker, which was synchronously amplified twice by recombinase polymerase amplification (RPA) coupled with transcription-mediated amplification (TMA), and then the products of the RPA-TMA reaction were quantitatively detected using a gold nanoparticle-based colorimetric assay. We established proof-of-concept evidence for this approach using TEXs from nasopharyngeal carcinoma (NPC) cells, with a detection limit of 102 particles/mL, and reported the measurement of plasma Epstein-Barr virus latent membrane protein 1 (LPM1)-positive (LMP1+, accuracy: 0.956) and epidermal growth factor receptor (EGFR)-positive (EGFR+, accuracy: 0.906) TEXs as potent early diagnostic biomarkers for NPC.


Assuntos
Biomarcadores Tumorais/isolamento & purificação , Carcinoma/sangue , DNA/isolamento & purificação , Exossomos/genética , Neoplasias Nasofaríngeas/sangue , Biomarcadores Tumorais/sangue , DNA/sangue , Receptores ErbB/sangue , Receptores ErbB/isolamento & purificação , Humanos , Carcinoma Nasofaríngeo , Recombinases/química , Proteínas da Matriz Viral/sangue , Proteínas da Matriz Viral/isolamento & purificação
19.
ACS Appl Mater Interfaces ; 8(31): 20329-41, 2016 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-27459593

RESUMO

Poly(styrene-b-(ethylene-co-butylene)-b-styrene) triblock copolymer (SEBS) was selected for functionalization and cross-linking reaction to prepare the anion exchange membrane. The cross-linked quaternized SEBS (QSEBS-Cn) membranes were synthesized by simultaneous of quaternization and cross-linking of chloromethylated SEBS with α,ω-difunctional tertiary amines. The spacer groups of (-CH2-)n in diamines did affect the functionalization, micromorphology and properties of the resulting QSEBS-Cn membranes. The ionic conductivity of QSEBS-Cn membranes greatly increased and methanol resistance slightly decreased with increasing the length of spacer groups in the cross-linked structures from -(CH2)- to -(CH2)6-. Compared to the un-cross-linked QSEBS, the QSEBS-Cn membranes behaved much higher mechanical property, service temperature, chemical stability and thermal stability. Moreover, the hybrid composite membrane of QSEBS-C6 with 0.5% of graphene oxide could also be in situ prepared. This hybrid membrane had both relatively high ionic conductivity of 2.0 × 10(-2) S·cm(-1) and high selectivity of 7.6 × 10(4) S·s·cm(-3) at 60 °C due to its low methanol permeability.

20.
J Phys Chem B ; 120(27): 6890-6, 2016 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-27337066

RESUMO

We developed a linear combination of two Flory's melting-point theories, one for stretched and the other for solution polymers, to predict the melting point of stretched solution polymers. The dependences of the melting strains on varying temperatures, polymer volume fractions, and solvent qualities were verified by the onset strains of crystallization in our dynamic Monte Carlo simulations of stretched solution polymers under a constant strain rate. In addition, owing to phase separation before crystallization in a poor solvent, calibration of polymer concentration to the polymer-rich phase appears necessary for the verification. Our results set up a preliminary thermodynamic background for the investigation of the multicomponent effect on strain-induced crystallization of polymers in rubbers and gels as well as on shear-induced crystallization of polymers in solutions and blends.

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