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1.
Mol Med ; 29(1): 113, 2023 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-37605109

RESUMO

OBJECTIVE: To elucidate the mechanism whereby advanced glycation end products (AGEs) accelerate atherosclerosis (AS) and to explore novel therapeutic strategies for atherosclerotic cardiovascular disease. METHODS AND RESULTS: The effect of AGEs on low-density lipoprotein (LDL) transcytosis across endothelial cells (ECs) was assessed using an in vitro model of LDL transcytosis. We observed that AGEs activated the receptor for advanced glycation end products (RAGE) on the surface of ECs and consequently upregulated Caveolin-1, which in turn increased caveolae-mediated LDL transcytosis and accelerated AS progression. Our molecular assessment revealed that AGEs activate the RAGE-NF-κB signaling, which then recruits the NF-κB subunit p65 to the RAGE promoter and consequently enhances RAGE transcription, thereby forming a positive feedback loop between the NF-κB signaling and RAGE expression. Increased NF-κB signaling ultimately upregulated Caveolin-1, promoting LDL transcytosis, and inhibition of RAGE suppressed AGE-induced LDL transcytosis. In ApoE-/- mice on a high-fat diet, atherosclerotic plaque formation was accelerated by AGEs but suppressed by EC-specific knockdown of RAGE. CONCLUSION: AGEs accelerate the development of diabetes-related AS by increasing the LDL transcytosis in ECs through the activation of the RAGE/NF-κB/Caveolin-1 axis, which may be targeted to prevent or treat diabetic macrovascular complications.


Assuntos
Aterosclerose , NF-kappa B , Animais , Camundongos , Receptor para Produtos Finais de Glicação Avançada/genética , Caveolina 1/genética , Células Endoteliais , Transcitose , Produtos Finais de Glicação Avançada
2.
Am J Physiol Endocrinol Metab ; 322(2): E165-E172, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34843659

RESUMO

Long-term sleep deprivation (SD) is a bad lifestyle habit, especially among specific occupational practitioners, characterized by circadian rhythm misalignment and abnormal sleep/wake cycles. SD is closely associated with an increased risk of metabolic disturbance, particularly obesity and insulin resistance. The incretin hormone, glucagon-like peptide-1 (GLP-1), is a critical insulin release determinant secreted by the intestinal L-cell upon food intake. Besides, the gut microbiota participates in metabolic homeostasis and regulates GLP-1 release in a circadian rhythm manner. As a commonly recognized intestinal probiotic, Bifidobacterium has various clinical indications regarding its curative effect. However, few studies have investigated the effect of Bifidobacterium supplementation on sleep disorders. In the present study, we explored the impact of long-term SD on the endocrine metabolism of rhesus monkeys and determined the effect of Bifidobacterium supplementation on the SD-induced metabolic status. Lipid concentrations, body weight, fast blood glucose, and insulin levels increased after SD. Furthermore, after 2 mo of long-term SD, the intravenous glucose tolerance test showed that the glucose metabolism was impaired and the insulin sensitivity decreased. Moreover, 1 mo of Bifidobacterium oral administration significantly reduced blood glucose and attenuated insulin resistance in rhesus macaques. Overall, our results suggested that Bifidobacterium might be used to alleviate SD-induced aberrant glucose metabolism and improve insulin resistance. Also, it might help in better understanding the mechanisms governing the beneficial effects of Bifidobacterium.NEW & NOTEWORTHY Our findings demonstrated that long-term sleep deprivation is closely associated with metabolic syndromes. Bifidobacterium administration showed a superior effect on insulin resistance caused by sleep deprivation. Overall, we provide prevention and treatment methods for long-term sleep deprivation, a bad lifestyle habit among specific occupational practitioners, such as irregular shift workers.


Assuntos
Bifidobacterium , Suplementos Nutricionais , Resistência à Insulina , Privação do Sono/complicações , Privação do Sono/dietoterapia , Animais , Glicemia/análise , Glicemia/metabolismo , Peso Corporal , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Ritmo Circadiano , Modelos Animais de Doenças , Polipeptídeo Inibidor Gástrico/sangue , Peptídeo 1 Semelhante ao Glucagon/sangue , Teste de Tolerância a Glucose , Incretinas/sangue , Insulina/sangue , Macaca mulatta , Masculino , Privação do Sono/sangue , Resultado do Tratamento , Triglicerídeos/sangue
3.
Biochem Biophys Res Commun ; 634: 189-195, 2022 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-36252499

RESUMO

Insulin resistance is a risk factor for type 2 diabetes and is often associated with obesity. Vaccarin, a flavonoid found in vaccaria seeds, is commonly used in traditional Chinese medicine for activating blood circulation. Here, we showed that vaccarin ameliorates high-fat diet-induced obesity and insulin resistance in mice by reducing fat accumulation and improving insulin sensitivity in white adipose tissue. Further hyperinsulinemic-euglycemic clamp test revealed enhanced glucose uptake in vaccarin-treated WAT and skeletal muscle, consistent with activated insulin signaling pathway in these tissues. Mechanistically, vaccarin activates adipose tissue GPR120 and subsequently activating the PI3K/AKT/GLUT4 signaling pathway in 3T3-L1 cells. Together, these results reveal an undiscovered function of vaccarin in preventing obesity-related insulin resistance and advocates that vaccarin holds promise for further development as an innovative agent for the prevention of metabolic disorders.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Transdução de Sinais , Animais , Camundongos , Diabetes Mellitus Tipo 2/metabolismo , Dieta Hiperlipídica/efeitos adversos , Glucose/metabolismo , Insulina , Resistência à Insulina/fisiologia , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo
4.
Biochem Biophys Res Commun ; 632: 139-149, 2022 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-36209582

RESUMO

Obesity and related metabolic disorders are worldwide epidemics. Current lifestyle interventions and drug treatment for obesity seem insufficient. Here, we show that Loureirin B (LB), a major flavonoid molecule extracted from Sanguis Draxonis, prevents diet-induced obesity and ameliorates concomitant metabolic abnormalities including fatty liver, insulin resistance and systemic inflammation in mice. Mechanistically, LB treatment increases the proportion of ω3 polyunsaturated fatty acids (PUFAs) in brown adipose tissue (BAT) and white adipose tissue (WAT), which subsequently activates the key lipid sensor GPR120. In line with this, LB treatment promotes browning of WAT and activates BAT thermogenesis through upregulation of UCP1, a downstream effector of GPR120. Conversely, inhibition of GPR120 abolishes the thermogenic effect of LB in primary cultured brown adipocytes. Together, these results suggest that LB possesses anti-obesity property by enhancing adipose tissue thermogenesis via activation of ω3 PUFA-GPR120-UCP1 axis and holds promises for combating obesity and its related metabolic syndrome.


Assuntos
Tecido Adiposo Marrom , Ácidos Graxos Ômega-3 , Obesidade , Animais , Camundongos , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/metabolismo , Dieta Hiperlipídica/efeitos adversos , Metabolismo Energético , Ácidos Graxos Ômega-3/metabolismo , Flavonoides/farmacologia , Camundongos Endogâmicos C57BL , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Termogênese , Proteína Desacopladora 1/metabolismo , Resinas Vegetais/farmacologia , Resinas Vegetais/uso terapêutico , Receptores Acoplados a Proteínas G/metabolismo
5.
Small ; 18(21): e2201548, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35491513

RESUMO

Adequately harvesting all excitons in a single molecule and inhibiting exciton losses caused by intermolecular interactions are two important factors for achieving high efficiencies thermally activated delayed fluorescence (TADF). One potential approach for optimizing these is to tune alignment of various excited state energy levels by using different doping concentrations. Unfortunately, emission efficiencies of most TADF emitters decrease rapidly with concentrations which limits the window for energy level tunning. In this work, by introducing a spiro group to increase steric hindrance of a TADF emitter (BPPXZ) with a phenoxazine and a dibenzo[a,c]phenazine, emission efficiency of the resulting molecule (BPSPXZ) is much less affected by concentration increase. This enables exploitation of the concentration effects to tune energy levels of its excited states for obtaining simultaneously small singlet-triplet energy offset and large spin-orbital coupling, leading to high-efficiency reverse intersystem crossing. With these merits, organic light-emitting diodes (OLEDs) using the BPSPXZ emitter from 5 to 60 wt% doping can all deliver EQE of over 20%. More importantly, record-high EQEs of 33.4% and 15.8% are respectively achieved in the optimized and nondoped conditions. This work proposes a strategy for developing red TADF emitters by optimizing the intermolecular interaction and energy level alignments to facilitate exciton utilization over wide doping concentrations.

6.
Hepatobiliary Pancreat Dis Int ; 21(6): 543-550, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35705443

RESUMO

BACKGROUND: Early recurrence results in poor prognosis of patients with hepatocellular carcinoma (HCC) after liver transplantation (LT). This study aimed to explore the value of computed tomography (CT)-based radiomics nomogram in predicting early recurrence of patients with HCC after LT. METHODS: A cohort of 151 patients with HCC who underwent LT between December 2013 and July 2019 were retrospectively enrolled. A total of 1218 features were extracted from enhanced CT images. The least absolute shrinkage and selection operator algorithm (LASSO) logistic regression was used for dimension reduction and radiomics signature building. The clinical model was constructed after the analysis of clinical factors, and the nomogram was constructed by introducing the radiomics signature into the clinical model. The predictive performance and clinical usefulness of the three models were evaluated using receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA), respectively. Calibration curves were plotted to assess the calibration of the nomogram. RESULTS: There were significant differences in radiomics signature among early recurrence patients and non-early recurrence patients in the training cohort (P < 0.001) and validation cohort (P < 0.001). The nomogram showed the best predictive performance, with the largest area under the ROC curve in the training (0.882) and validation (0.917) cohorts. Hosmer-Lemeshow testing confirmed that the nomogram showed good calibration in the training (P = 0.138) and validation (P = 0.396) cohorts. DCA showed if the threshold probability is within 0.06-1, the nomogram had better clinical usefulness than the clinical model. CONCLUSIONS: Our CT-based radiomics nomogram can preoperatively predict the risk of early recurrence in patients with HCC after LT.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Transplante de Fígado , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/patologia , Nomogramas , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/patologia , Transplante de Fígado/efeitos adversos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos
7.
BMC Geriatr ; 21(1): 452, 2021 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-34348649

RESUMO

BACKGROUND: Aging is a natural life process and with an aging population, age-related diseases (e.g. type 2 diabetes mellitus (T2DM), atherosclerosis-based cardiovascular diseases) are the primary mortality cause in older adults. Telomerase is often used as an aging biomarker. Detection and characterization of novel biomarkers can help in a more specific and sensitive identification of a person's aging status. Also, this could help in age-related diseases early prevent, ultimately prolonging the population's life span. Sirtuin 6 (Sirt6) - a member of the Sirtuins NAD+-dependent histone deacetylases family - is mainly intracellularly expressed, and is reported to be involved in the regulation of aging and aging-related diseases. Whether serum Sirt6 is correlated with aging and could be used as an aging biomarker is unknown. In the present study, we aimed to investigate the age-related Sirt6 changes in the serum of human adults. METHODS: Participants were divided into three groups according to age: 20-30 years (Young); 45-55 years (Middle-aged); and ≥ 70 years (Old). The Sirt6 and telomerase serum concentrations were determined by ELISA. The Sirt6 and human telomerase reverse transcriptase (hTERT) expression in vessels from amputated human lower limbs were analyzed using real-time quantitative PCR (RT-qPCR) and immunohistochemical staining. The relationships between variables were evaluated by Pearson correlation analysis. RESULTS: The Sirt6 and telomerase serum levels reduced with an increase in age. A similar tendency was observed for Sirt6 and hTERT in the vessel. Serum levels of Sirt6 were higher in females compared with males. Pearson's regression analysis revealed that the Sirt6 serum level positively correlated with telomerase (r = 0.5743) and both were significantly negatively correlated with age (r = - 0.5830 and r = - 0.5993, respectively). CONCLUSIONS: We reported a negative correlation between serum Sirt6 concentration and aging in human beings. Therefore, the Sirt6 serum level is a potential sex-specific aging marker.


Assuntos
Envelhecimento , Diabetes Mellitus Tipo 2 , Sirtuínas , Adulto , Idoso , Biomarcadores , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sirtuínas/sangue , Adulto Jovem
8.
Chin J Traumatol ; 24(6): 328-332, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34511323

RESUMO

PURPOSE: Rapid decompressive craniectomy (DC) was the most effective method for the treatment of hypertensive intracerebral hemorrhage (HICH) with cerebral hernia, but the mortality and disability rate is still high. We suspected that hematoma puncture drainage (PD) + DC may improve the therapeutic effect and thus compared the combined surgery with DC alone. METHODS: From December 2013 to July 2019, patients with HICH from Linzhi, Tibet and Honghe, Yunnan Province were retrospectively analyzed. The selection criteria were as follows: (1) altitude ≥1500 m; (2) HICH patients with cerebral hernia; (3) Glascow coma scale score of 4-8 and time from onset to admission ≤3 h; (4) good liver and kidney function; and (5) complete case data. The included patients were divided into DC group and PD + DC group. The patients were followed up for 6 months. The outcome was assessed by Glasgow outcome scale (GOS) score, Kaplan-Meier survival curve and correlation between time from admission to operation and prognosis. A good outcome was defined as independent (GOS score, 4-5) and poor outcome defined as dependent (GOS score, 3-1). All data analyses were performed using SPSS 19, and comparison between two groups was conducted using separate t-tests or Chi-square tests. RESULTS: A total of 65 patients was included. The age ranged 34-90 years (mean, 63.00 ± 14.04 years). Among them, 31 patients had the operation of PD + DC, whereas 34 patients underwent DC. The two groups had no significant difference in the basic characteristics. After 6 months of follow-up, in the PD + DC group there were 8 death, 4 vegetative state, 4 severe disability (GOS score 1-3, poor outcome 51.6 %); 8 moderate disability, and 7 good recovery (GOS score 4-5, good outcome 48.4 %); while in the DC group the result was 15 death, 6 vegetative state, 5 severe disability (poor outcome 76.5 %), 4 moderate disability and 4 good recovery (good outcome 23.5 %). The GOS score and good outcome were significantly less in DC group than in PD + DC group (Z = -1.993, p = 0.046; χ2 = 4.38, p = 0.043). However, there was no significant difference regarding the survival curve between PD + DC group and DC group. The correlation between the time from admission to operation and GOS at 6 months (r = -0.41, R2 = 0.002, p = 0.829) was not significant in the PD + DC group, but significant in the DC group (r = -0.357, R2 = 0.128, p = 0.038). CONCLUSION: PD + DC treatment can improve the good outcomes better than DC treatment for HICH with cerebral hernia at a high altitude.


Assuntos
Craniectomia Descompressiva , Hemorragia Intracraniana Hipertensiva , Adulto , Idoso , Idoso de 80 Anos ou mais , Altitude , China , Drenagem , Encefalocele/cirurgia , Hematoma , Humanos , Hemorragia Intracraniana Hipertensiva/cirurgia , Pessoa de Meia-Idade , Prognóstico , Punções , Estudos Retrospectivos , Resultado do Tratamento
9.
Angew Chem Int Ed Engl ; 60(5): 2478-2484, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33080106

RESUMO

Developing red thermally activated delayed fluorescence (TADF) emitters for high-performance OLEDs is still facing great challenge. Herein, three red TADF emitters, pDBBPZ-DPXZ, pDTBPZ-DPXZ, and oDTBPZ-DPXZ, are designed and synthesized with same donor-acceptor (D-A) backbone with different peripheral groups attaching on the A moieties. Their lowest triplet states change from locally excited to charge transfer character leading to significantly enhance reverse intersystem crossing process. In particular, oDTBPZ-DPXZ exhibits efficient TADF feature and exciton utilization. It not only achieves an external quantum efficiency (EQE) of 20.1 % in red vacuum-processed OLED, but also realize a high EQE of 18.5 % in a solution-processed OLED, which is among the best results in solution-processed red TADF OLEDs. This work provides an effective strategy for designing red TADF molecules by managing energy level alignments to facilitate the up-conversion process and thus enhance exciton harvesting.

10.
Angew Chem Int Ed Engl ; 60(49): 25878-25883, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34585471

RESUMO

The conformational distribution and mutual interconversion of thermally activated delayed fluorescence (TADF) emitters significantly affect the exciton utilization. However, their influence on the photophysics in amorphous film states is still not known due to the lack of a suitable quantitative analysis method. Herein, we used temperature-dependent time-resolved photoluminescence spectroscopy to quantitatively measure the relative populations of the conformations of a TADF emitter for the first time. We further propose a new concept of "self-doping" for realizing high-efficiency nondoped OLEDs. Interestingly, this "compositionally" pure film actually behaves as a film with a dopant (quasi-equatorial form) in a matrix (quasi-axial form). The concentration-induced quenching that may occur at high concentrations is thus expected to be effectively relieved. The "self-doping" OLED prepared with the newly developed TADF emitter TP2P-PXZ as a neat emitting layer realizes a high maximum external quantum efficiency of 25.4 % and neglectable efficiency roll-off.

11.
Small ; 16(34): e2002672, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32697430

RESUMO

Multi-modality imaging-guided cancer therapy is considered as a powerful theranostic platform enabling simultaneous precise diagnosis and treatment of cancer. However, recently reported multifunctional systems with multiple components and sophisticate structures remain major obstacles for further clinical translation. In this work, a single-photomolecular theranostic nanoplatform is fabricated via a facile nanoprecipitation strategy. By encapsulating a semiconductor oligomer (IT-S) into an amphiphilic lipid, water-dispersible IT-S nanoparticles (IT-S NPs) are prepared. The obtained IT-S NPs have a very simple construction and possess ultra-stable near-infrared (NIR) fluorescence (FL)/photoacoustic (PA) dual-modal imaging and high photothermal conversion efficiency of 72.3%. Accurate spatiotemporal distribution profiles of IT-S NPs are successfully visualized by NIR FL/PA dual-modal imaging. With the comprehensive in vivo imaging information provided by IT-S NPs, tumor photothermal ablation is readily realized under precise manipulation of laser irradiation, which greatly improves the therapeutic efficacy without any obvious side effects. Therefore, the IT-S NPs allow high tumor therapeutic efficacy under the precise guidance of FL/PA imaging techniques and thus hold great potential as an effective theranostic platform for future clinical applications.


Assuntos
Hipertermia Induzida , Nanopartículas , Neoplasias , Técnicas Fotoacústicas , Linhagem Celular Tumoral , Humanos , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Imagem Óptica , Fototerapia , Nanomedicina Teranóstica
12.
Bull Environ Contam Toxicol ; 104(5): 707-713, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32222794

RESUMO

Fate of 2,4,6-tribromophenol (TBP) in environmental matrices is obscure. We used 14C-tracer to investigated mineralization, transformation, and non-extractable residue (NER)-formation of TBP in a soil under continuously oxic, continuously anoxic, and anoxic-oxic alteration conditions. In all cases, TBP rapidly dissipated, mineralized to CO2, and formed NERs in the soil. Considerable amounts of transformation products (2-12%) were detected during the incubation. Marked mineralization (13-26%) indicated that soil microorganisms used TBP as their energy source. About 62-70% of the initial radioactivity was transformed into NERs, being mainly attributed to binding to humic and fulvic acid fractions. TBP transformation was significantly faster under oxic conditions than under anoxic conditions, and was boosted when the soil redox changed from anoxic to oxic state. The results provide new insights into fate of TBP in soil and suggest the importance to evaluate the stability of NERs for risk assessment of TBP in soil.


Assuntos
Minerais/análise , Fenóis/análise , Poluentes do Solo/análise , Solo/química , Benzopiranos/análise , Substâncias Húmicas/análise , Oxirredução
13.
Circulation ; 138(4): 397-411, 2018 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-29431644

RESUMO

BACKGROUND: Nitrates are widely used to treat coronary artery disease, but their therapeutic value is compromised by nitrate tolerance, because of the dysfunction of prostaglandin I2 synthase (PTGIS). MicroRNAs repress target gene expression and are recognized as important epigenetic regulators of endothelial function. The aim of this study was to determine whether nitrates induce nitrovasodilator resistance via microRNA-dependent repression of PTGIS gene expression. METHODS: Nitrovasodilator resistance was induced by nitroglycerin (100 mg·kg-1·d-1, 3 days) infusion in Apoe-/- mice. The responses of aortic arteries to nitric oxide donors were assessed in an organ chamber. The expression levels of microRNA-199 (miR-199)a/b were assayed by quantitative reverse transcription polymerase chain reaction or fluorescent in situ hybridization. RESULTS: In cultured human umbilical vein endothelial cells, nitric oxide donors induced miR-199a/b endogenous expression and downregulated PTGIS gene expression, both of which were reversed by 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide potassium salt or silence of serum response factor. Evidence from computational and luciferase reporter gene analyses indicates that the seed sequence of 976 to 982 in the 3'-untranslated region of PTGIS mRNA is a target of miR-199a/b. Gain functions of miR-199a/b resulting from chemical mimics or adenovirus-mediated overexpression increased PTGIS mRNA degradation in HEK293 cells and human umbilical vein endothelial cells. Furthermore, nitroglycerin-decreased PTGIS gene expression was prevented by miR-199a/b antagomirs or was mirrored by the enforced expression of miR-199a/b in human umbilical vein endothelial cells. In Apoe-/- mice, nitroglycerin induced the ectopic expression of miR-199a/b in the carotid arterial endothelium, decreased PTGIS gene expression, and instigated nitrovasodilator resistance, all of which were abrogated by miR-199a/b antagomirs or LNA-anti-miR-199. It is important that the effects of miR-199a/b inhibitions were abolished by adenovirus-mediated PTGIS deficiency. Moreover, the enforced expression of miR-199a/b in vivo repressed PTGIS gene expression and impaired the responses of aortic arteries to nitroglycerin/sodium nitroprusside/acetylcholine/cinaciguat/riociguat, whereas the exogenous expression of the PTGIS gene prevented nitrovasodilator resistance in Apoe-/- mice subjected to nitroglycerin infusion or miR-199a/b overexpression. Finally, indomethacin, iloprost, and SQ29548 improved vasorelaxation in nitroglycerin-infused Apoe-/- mice, whereas U51605 induced nitrovasodilator resistance. In humans, the increased expressions of miR-199a/b were closely associated with nitrate tolerance. CONCLUSIONS: Nitric oxide-induced ectopic expression of miR-199a/b in endothelial cells is required for nitrovasodilator resistance via the repression of PTGIS gene expression. Clinically, miR-199a/b is a novel target for the treatment of nitrate tolerance.


Assuntos
Aorta/efeitos dos fármacos , Sistema Enzimático do Citocromo P-450/metabolismo , Resistência a Medicamentos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Oxirredutases Intramoleculares/metabolismo , Doadores de Óxido Nítrico/farmacologia , Óxido Nítrico/metabolismo , Nitroglicerina/farmacologia , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologia , Animais , Aorta/enzimologia , Sistema Enzimático do Citocromo P-450/genética , Resistência a Medicamentos/genética , Células HEK293 , Células Endoteliais da Veia Umbilical Humana/enzimologia , Humanos , Oxirredutases Intramoleculares/genética , Masculino , Camundongos Knockout para ApoE , MicroRNAs/genética , MicroRNAs/metabolismo , Doadores de Óxido Nítrico/metabolismo , Nitroglicerina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima , Vasodilatadores/metabolismo
14.
Small ; 15(38): e1903121, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31379108

RESUMO

The combination of diagnostic and therapeutic functions in a single theranostic nanoagent generally requires the integration of multi-ingredients. Herein, a cytotoxic near-infrared (NIR) dye (IR-797) and its nanoassembly are reported for multifunctional cancer theranostics. The hydrophobic IR-797 molecules are self-assembled into nanoparticles, which are further modified with an amphiphilic polymer (C18PMH-PEG5000) on the surface. The prepared PEG-IR-797 nanoparticles (PEG-IR-797 NPs) possess inherent cytotoxicity from the IR-797 dye and work as a chemotherapeutic drug which induces apoptosis of cancer cells. The IR-797 NPs are found to have an ultrahigh mass extinction coefficient (444.3 L g-1 cm-1 at 797 nm and 385.9 L g-1 cm-1 at 808 nm) beyond all reported organic nanomaterials (<40 L g-1 cm-1 ) for superior photothermal therapy (PTT). In addition, IR-797 shows some aggregation-induced-emission (AIE) properties. Combining the merits of good NIR absorption, high photothermal energy conversion efficiency, and AIE, makes the PEG-IR-797 NPs useful for multimodal NIR AIE fluorescence, photoacoustic, and thermal imaging-guided therapy. The research exhibits the possibility of using a single ingredient and entity to perform multimodal NIR fluorescence, photoacoustic, and thermal imaging-guided chemo-/photothermal combination therapy, which may trigger wide interest from the fields of nanomedicine and medicinal chemistry to explore multifunctional theranostic organic molecules.


Assuntos
Antineoplásicos/química , Nanomedicina Teranóstica/métodos , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Técnicas Fotoacústicas/métodos , Fotoquimioterapia/métodos , Polímeros/química
15.
Angew Chem Int Ed Engl ; 58(41): 14660-14665, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31313424

RESUMO

Developing red thermally activated delayed fluorescence (TADF) emitters, attainable for both high-efficient red organic light-emitting diodes (OLEDs) and non-doped deep red/near-infrared (NIR) OLEDs, is challenging. Now, two red emitters, BPPZ-PXZ and mDPBPZ-PXZ, with twisted donor-acceptor structures were designed and synthesized to study molecular design strategies of high-efficiency red TADF emitters. BPPZ-PXZ employs the strictest molecular restrictions to suppress energy loss and realizes red emission with a photoluminescence quantum yield (ΦPL ) of 100±0.8 % and external quantum efficiency (EQE) of 25.2 % in a doped OLED. Its non-doped OLED has an EQE of 2.5 % owing to unavoidable intermolecular π-π interactions. mDPBPZ-PXZ releases two pyridine substituents from its fused acceptor moiety. Although mDPBPZ-PXZ realizes a lower EQE of 21.7 % in the doped OLED, its non-doped device shows a superior EQE of 5.2 % with a deep red/NIR emission at peak of 680 nm.

16.
Arterioscler Thromb Vasc Biol ; 37(5): 957-968, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28254819

RESUMO

OBJECTIVE: To identify circulating microRNAs that are differentially expressed in severe coronary heart disease with well or poorly developed collateral arteries and to investigate their mechanisms of action in vivo and in vitro. APPROACH AND RESULTS: In our study, we identified a circulating microRNA, miR-15b-5p, with low expression that, nevertheless, characterized patients with sufficient coronary collateral artery function. Moreover, in murine hindlimb ischemia model, in situ hybridization identified that miR-15b-5p was specifically expressed in vascular endothelial cells of adductors in sham group and was remarkably downregulated after femoral artery ligation. Overexpressed miR-15b-5p significantly inhibited arteriogenesis and angiogenesis in mice. In vitro, both under basal and vascular endothelial growth factor stimulation, loss-of-function or gain-of-function studies suggested that miR-15b-5p significantly promoted or depressed the migration and proliferation of endothelial cells. We identified AKT3 (protein kinase B-3) as a direct target of miR-15b-5p. Interestingly, AKT3 deficiency by injection with Chol-AKT3-siRNA obviously suppressed arteriogenesis and the recovery of blood perfusion after femoral ligation in mice. CONCLUSIONS: These results indicate that circulating miR-15b-5p is a suitable biomarker for discriminating between patients with well-developed or poorly developed collaterals. Moreover, miR-15b-5p is a key regulator of arteriogenesis and angiogenesis, which may represent a potential therapeutic target for ischemic disease.


Assuntos
Circulação Colateral , Doença da Artéria Coronariana/enzimologia , Circulação Coronária , Vasos Coronários/enzimologia , Isquemia/enzimologia , MicroRNAs/metabolismo , Músculo Esquelético/irrigação sanguínea , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Movimento Celular , Proliferação de Células , Células Cultivadas , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/fisiopatologia , Vasos Coronários/fisiopatologia , Modelos Animais de Doenças , Membro Posterior , Humanos , Isquemia/genética , Isquemia/fisiopatologia , Masculino , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Neovascularização Fisiológica , Proteínas Proto-Oncogênicas c-akt/genética , Interferência de RNA , Transdução de Sinais , Transfecção
17.
Appl Opt ; 57(18): D141-D144, 2018 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-30117947

RESUMO

A rule of thumb, denoted as IGA-rule 17, has been developed to describe the temperature and cutoff wavelength-dependent dark currents of wavelength-extended InGaAs photodetectors in a 2-3 µm band. The validity and limitations of the rule are discussed. This rule is intended as an index for device developers to evaluate their technologies in processing, a simple tool for device users to estimate reachable performance at various conditions in their design, and an effective bridge between the two.

18.
Zhonghua Nan Ke Xue ; 24(2): 147-151, 2018 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-30156075

RESUMO

OBJECTIVE: To investigate the prevalence of Ureaplasma urealyticum (UU) infection in infertile men, its influence on routine semen parameters and the distribution of antisperm antibody (AsAb) and its types in infertile patients with UU infection. METHODS: We detected the positive rate of UU infection, semen parameters, and the distribution of AsAb and its types in 662 infertile men and 25 normal fertile male controls followed by comparison of the obtained data between the two groups of subjects. RESULTS: The positive rate of UU infection was significantly higher in the infertile men than in the normal controls (52.87% ï¼»350/662ï¼½ vs 16.00% ï¼»4/25ï¼½, χ2 = 11.68, P <0.05). The semen volume, sperm count, sperm concentration and percentage of progressively motile sperm were remarkably lower in the UU-positive infertile males than in the control group (P <0.05). No statistically significant difference was observed between the UU-positive and UU-negative groups in the positive rates of total AsAb (43.4% vs 36.5%, χ2 = 3.25, P >0.05) and AsAb IgA, IgM and IgG in the seminal plasma, or in the percentages of serum AsAb IgM (16.9% vs 20.5%, χ2 = 1.22, P >0.05) and IgG (32.7% vs 28.9%, χ2 = 0.99, P >0.05) except in that of serum AsAb IgA (23.6% vs 17.0%, χ2 = 4.03, P <0.05). CONCLUSIONS: The UU infection rate is high in infertile males, which decreases the semen volume, total sperm count, motile sperm concentration and percentage of progressively motile sperm and increases the positive rate of serum AsAb IgA.


Assuntos
Anticorpos Antibacterianos/análise , Infertilidade Masculina/microbiologia , Espermatozoides/imunologia , Infecções por Ureaplasma/diagnóstico , Ureaplasma urealyticum/imunologia , Humanos , Infertilidade Masculina/imunologia , Masculino , Sêmen , Contagem de Espermatozoides , Infecções por Ureaplasma/imunologia
19.
Zhonghua Nan Ke Xue ; 23(2): 183-188, 2017 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-29658260

RESUMO

Infertility can be attributed to reproductive tract infections (RTI), most commonly nongonococcal urethritis, mainly including Mycoplasma and Chlamydia infections, which may directly or indirectly damage spermatozoa and spermatogenic cells. In addition, a series of immune responses caused by such infections are also associated with male infertility. Methods for the clinical detection of these microbial infections are being constantly improved for more specific and precise control over the impact of Mycoplasma and Chlamydia infections on male fertility.


Assuntos
Infecções por Chlamydia/complicações , Infertilidade Masculina/microbiologia , Infecções por Mycoplasma/complicações , Uretrite/microbiologia , Humanos , Masculino , Mycoplasma , Infecções do Sistema Genital , Espermatozoides/microbiologia , Uretrite/complicações
20.
Zhonghua Nan Ke Xue ; 23(4): 329-336, 2017 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-29714418

RESUMO

OBJECTIVE: Sperm DNA fragmentation (SDF) is widely used to predict male infertility and the methods of detecting SDF are varied. This study aimed to compare two methods of SDF detection and investigate the correlation between SDF and sperm quality. METHODS: Using sperm chromatin structure assay (SCSA) and sperm chromatin dispersion test (SCD), we detected SDF in 108 semen samples collected in the Center of Reproduction and Genetics of Suzhou Municipal Hospital. We compared the results of the two methods and analyzed the correlations of SDF routine semen parameters, sperm morphology and the age of the patients. RESULTS: A significant consistency was found in the SDF index (DFI) between the two methods (P<0.01). The DFI was correlated negatively with sperm motility, the percentage of progressively motile sperm, and that of morphologically normal sperm (P <0.01), but positively with the teratozoospermia index (P <0.01 in SCSA and P <0.05 in SCD). The DFI measured by SCSA showed a significantly positive correlation with the patients' age (P <0.01), but not that obtained by SCD. CONCLUSIONS: The results of both SCSA and SCD play an important role in predicting sperm quality. As a clinical index, the DFI has a predictive value for male infertility. However, the results of different detecting methods vary widely, which calls for further studies on their standardization.


Assuntos
Cromatina/fisiologia , Fragmentação do DNA , Infertilidade Masculina/diagnóstico , Sêmen/fisiologia , Espermatozoides/fisiologia , Cromatina/genética , Humanos , Masculino , Análise do Sêmen , Motilidade dos Espermatozoides , Espermatozoides/ultraestrutura
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