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BACKGROUND: Abnormal heart rate recovery (HRR), representing cardiac autonomic dysfunction, is an important predictor of cardiovascular disease. Prolonged sedentary time (ST) is associated with a slower HRR. However, it is not clear how much moderate-to-vigorous physical activity (MVPA) is required to mitigate the adverse effects of sedentary behavior on HRR in young and middle-aged adults. This study aimed to examine the joint association of ST and MVPA with abnormal HRR in this population. METHODS: A cross-sectional analysis was conducted on 1253 participants (aged 20-50 years, 67.8% male) from an observational study assessing cardiopulmonary fitness in Fujian Province, China. HRR measured via cardiopulmonary exercise tests on a treadmill was calculated as the difference between heart rate at peak exercise and 2 min after exercise. When the HRR was ≤ 42 beats·minute-1 within this time, it was considered abnormal. ST and MVPA were assessed by the IPAQ-LF. Individuals were classified as having a low sedentary time (LST [< 6 h·day-1]) or high sedentary time (HST [≥ 6 h·day-1]) and according to their MVPA level (low MVPA [0-149 min·week-1], medium MVPA [150-299 min·week-1], high MVPA [≥ 300 min·week-1]). Finally, six ST-MVPA groups were derived. Associations between ST-MVPA groups with abnormal HRR incidence were examined using logistic regression models. RESULTS: 53.1% of the young and middle-aged adults had less than 300 min of MVPA per week. In model 2, adjusted for possible confounders (e.g. age, sex, current smoking status, current alcohol consumption, sleep status, body mass index), HST was associated with higher odds of an abnormal HRR compared to LST (odds ratio (OR) = 1.473, 95% confidence interval (CI) = 1.172-1.852). Compared with the reference group (HST and low MVPA), the HST and high MVPA groups have a lower chance of abnormal HRR (OR, 95% CI = 0.553, 0.385-0.795). Compared with individuals with HST and low MVPA, regardless of whether MVPA is low, medium, or high, the odds of abnormal HRR in individuals with LST is significantly reduced (OR, 95% CI = 0.515, 0.308-0.857 for LST and low MVPA; OR, 95% CI = 0.558, 0.345-0.902 for LST and medium MVPA; OR, 95% CI = 0.476, 0.326-0.668 for LST and high MVPA). CONCLUSION: Higher amounts of MVPA appears to mitigate the increased odds of an abnormal HRR associated with HST for healthy young and middle-aged adults.
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Exercício Físico , Frequência Cardíaca , Comportamento Sedentário , Humanos , Masculino , Feminino , Adulto , Estudos Transversais , Frequência Cardíaca/fisiologia , Pessoa de Meia-Idade , Exercício Físico/fisiologia , China/epidemiologia , Adulto Jovem , Teste de EsforçoRESUMO
Multistimuli-responsive conductive hydrogels have been appealing candidates for multifunctional ionic skin. However, the fabrication of the multistimuli-responsive conductive hydrogels with satisfactory mechanical property to meet the practical applications is still a great challenge. In this study, a novel poly(N-isopropylacrylamide-co-sodium acrylate)/alginate/hectorite clay Laponite XLS (PNIPAM-SA/ALG/XLS) double cross-linked hydrogel with excellent mechanical property, self-recovery ability, temperature/pH-responsive ability, and strain/temperature-sensitive conductivity was fabricated. The PNSAX hydrogel possessed a moderate tensile strength of 290 kPa at a large elongation rate of 1120% and an excellent compression strength of 2.72 MPa at 90%. The hydrogel also possessed excellent mechanical repeatability and self-recovery ability. Thus, the hydrogel could withstand repetitive deformations for long time periods. Additionally, the hydrogel could change its transparency and volume once at a temperature of 44 °C and change its volume at different pHs. Thus, the visual temperature/pH-responsive ability allowed the hydrogel to qualitatively harvest environmental information. Moreover, the hydrogel possessed an excellent conductivity of 0.43 S/m, and the hydrogel could transform large/subtle deformation and temperature information into electrical signal change. Thus, the ultrafast strain/temperature-sensitive conductivity allowed the hydrogel to quantitatively detect large/small-scale human motions as well as environmental temperature. A cytotoxicity test confirmed the good cytocompatibility. Taken together, the hydrogel was suitable for human motion detecting and environmental information harvesting for long time periods. Therefore, the hydrogel has a great application potential as a multifunctional ionic skin and smart sensor.
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Hidrogéis , Pele , Humanos , Condutividade Elétrica , Íons , TemperaturaRESUMO
Sugars are abundant natural sources existing in biological systems, and bioactive saccharides have attracted much more attention in the field of biochemistry and biomaterials. For better understanding of the sugar-based biomaterials and biological sciences, aggregation-induced emission luminogens (AIE-gens) have been widely employed for detection, tracing, and imaging. This review covers the applications of AIE molecules on sugar-based biomaterials by three parts, polysaccharide, oligosaccharide, and monosaccharide, mainly focusing on saccharide detection, stimuli response materials preparation, bioimaging, and study of the AIE mechanism. These excellent works suggest the promising future of the sugar-based AIE bioconjugates, considering that the naturally designed and elaborately functionalized saccharides play discriminate roles in biological processes and AIE-tagged species may work as an indicator in each case. However, there are a lot of sugar-based biological species that have not been touched, such as mucopolysaccharides and glycoproteins on the cell surface and in the cell plasma. Based on these features, we enthusiastically look forward to more glorious developments in this bright research area.
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Quitosana/química , Corantes Fluorescentes/química , Estilbenos/química , Açúcares/análise , Configuração de Carboidratos , Células HeLa , Humanos , Imagem ÓpticaRESUMO
In this work, we report the fabrication and functional demonstration of a kind of dually responsive nanoparticles (NPs) as a potential drug delivery vector. The pH value, corresponding to the acidic microenvironment at the tumor site, and mannitol, to the extracellular trigger agent, were employed as the dually responsive factors. The function of dual responses was achieved by breaking the dynamic covalent bonds between phenylboronic acid (PBA) groups and diols at low pH value (pH 5.0) and/or under the administration of mannitol, which triggered the decomposition of the complex NPs and the concomitant release of anticancer drug of doxorubicin (DOX) loaded inside the NPs. The NPs were composed of modified chitosan (PQCS) with quaternary ammonium and PBA groups on the side chains, heparin (Hep), and poly(vinyl alcohol) (PVA), in which quaternary ammonium groups offer the positive charge for the cell-internalization of NPs, PBA groups serve for the formation of dynamic bonds in responding to pH change and mannitol addition, PVA furnishes the NPs with diol groups for the interaction with PBA groups and the formation of dynamic NPS, and Hep plays the roles of reducing the cytotoxicity of highly positively-charged chitosan and forming of complex NPs for DOX up-loading. A three-step fabrication process of drug-loaded NPs was described, and the characterization results were comprehensively demonstrated. The sustained drug release from the drug-loaded NPs displayed obvious pH and mannitol dependence. More specifically, the cumulative DOX release was increased more than 1.5-fold at pH 5.0 with 20 mg mL-1 mannitol. Furthermore, the nanoparticles were manifested with effective antitumor efficient and apparently enhanced cytotoxicity in response to the acidic pH value and/or mannitol.
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Compostos de Amônio , Quitosana , Nanopartículas , Quitosana/química , Doxorrubicina/química , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Concentração de Íons de Hidrogênio , Manitol , Nanopartículas/químicaRESUMO
A novel C16 tetranorditerpenoid, norcrassin A (1), and an unusual dimeric labdane-type diterpenoid, bicrotonol A (2), were isolated from the roots of Croton crassifolius. Norcrassin A (1) featured a new carbon skeleton with an unprecedented 5/5/5/6 tetracyclic system. Bicrotonol A (2) possessed an unusual tetrahydroxypyran ring linkage connecting two labdane diterpenoid monomers. The structures of all compounds, including the absolute configuration, were elucidated by the interpretation of their NMR spectroscopic data, high resolution mass spectrometry, and single-crystal X-ray diffraction. A plausible biosynthetic pathway of 1 is proposed. The anti-Alzheimer's Disease (AD) activities of 1 and 2 are also evaluated using the AD pathological model.
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Doença de Alzheimer/tratamento farmacológico , Croton/química , Diterpenos/química , Diterpenos/uso terapêutico , Raízes de Plantas/química , Animais , Animais Geneticamente Modificados , Caenorhabditis elegans/genética , Cristalografia por Raios X , Modelos Animais de Doenças , Diterpenos/isolamento & purificação , Humanos , Espectroscopia de Ressonância Magnética , Modelos MolecularesRESUMO
BACKGROUND: Phytosterols (PS), plant-derived natural steroid compounds, are novel feed additives to regulate immune function and promote pig growth. This study was conducted to determine the effects of PS on the immune response of weaned piglets. RESULTS: One hundred and twenty crossbred (Duroc × Landrace × Yorkshire) piglets with an average initial weight of 9.58 ± 0.26 kg were randomly allotted to three treatments. Treatments consisted of a control, PS (0.2 g kg-1 ) and polymyxin E (0.04 g kg-1 , antibiotic control) treatment. The results showed that PS or polymyxin E supplementation remarkably decreased diarrhea rate and elevated CD3+ CD4+ /CD3+ CD8+ ratio in piglets compared with the control (P < 0.05). PS increased basophil and serum interleukin-4, and caused a shift towards Th2 profile by decreasing Th1/Th2 ratios in piglets compared with control (P < 0.05). Polymyxin E contributed to an increase in interleukin-10 compared with the control (P < 0.05). No significant difference was observed in the amount of Lactobacillus, Bifidobacterium or Escherichia coli of jejunum among the three treatments (P > 0.05). CONCLUSION: These results suggest that PS supplementation has no significant effect on growth but could remarkably decrease diarrhea rate, and improve immunity and anti-inflammatory activity in weaned piglets. In addition, PS supplementation had similar effects on growth, anti-inflammation and intestinal microorganisms as supplementation with polymyxin E in piglets. © 2017 Society of Chemical Industry.
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Suplementos Nutricionais/análise , Fitosteróis/imunologia , Suínos/imunologia , Animais , Feminino , Imunidade , Interleucina-10/genética , Interleucina-10/imunologia , Interleucina-4/genética , Interleucina-4/imunologia , Intestinos/imunologia , Masculino , Fitosteróis/análise , Suínos/crescimento & desenvolvimento , DesmameRESUMO
BACKGROUND: Plant extracts have been used widely to improve growth, lower cholesterol, and exert antioxidative defense and antimicrobial activities in animal production. The present study aimed to investigate the effects of dietary phytosterols (PS) on growth performance, antioxidant enzymes and intestinal morphology in weaned piglets. RESULTS: A total of 120 crossbred piglets, weighing 9.58 ± 0.26 kg, were randomly allocated to three treatments: control, PS (0.2 g kg-1 ) and polymyxin E (0.04 g kg-1 , antibiotic control). Compared to the control, PS or polymyxin E supplementation decreased diarrhea rate, serum cholesterol and malondialdehyde (MDA) of the piglets (P < 0.05). Liver MDA was significantly decreased in PS-fed piglets compared to the control (P < 0.05), although there was no difference between the control and polymyxin E-fed piglets. PS increased the villous height/crypt depth ratio of the duodenum and jejunum compared to the control (P < 0.05). Polymyxin E supplementation in piglets did not alter the villous height/crypt depth ratio but raised the villous height and crypt depth of the duodenum compared to the control (P < 0.05). CONCLUSION: The results of the present study indicated that PS could decrease diarrhea rate, lower serum cholesterol, reduce lipid peroxidation and ameliorate intestinal morphology in weaned piglets. In addition, PS exerted better amelioration on intestinal morphology than polymyxin E in piglets. © 2017 Society of Chemical Industry.
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Antioxidantes/metabolismo , Diarreia/veterinária , Suplementos Nutricionais/análise , Intestinos/anatomia & histologia , Intestinos/efeitos dos fármacos , Fitosteróis/administração & dosagem , Suínos/crescimento & desenvolvimento , Animais , Catalase/metabolismo , Colesterol/sangue , Diarreia/tratamento farmacológico , Diarreia/enzimologia , Diarreia/fisiopatologia , Feminino , Glutationa Peroxidase/metabolismo , Intestinos/crescimento & desenvolvimento , Masculino , Malondialdeído/sangue , Superóxido Dismutase/metabolismo , Suínos/anatomia & histologia , Suínos/metabolismo , DesmameRESUMO
In the abstract, these sentences (page 1, line 5) should be: 'Additionally, hepatic betaine-homocysteine methyltransferase concentration as well as its mRNA abundance and lecithin level were found increased (P < 0. 05) by betaine supplementation in both basal diet-fed rats and high-fat diet-fed rats. Betaine administration in high-fat diet-fed rats exhibited a higher (P < 0.05) concentration of hepatic carnitine palmitoyltransferase 1 (CPT1) compared with high-fat diet-fed rats.'
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OBJECTIVE: To study the impact of the water extract from Codonopsis thalictrifolia Wall (CTW) on the reproductive METHODS: We divided 32 male SD infant rats into four groups of equal number to be treated intragastrical-system of male infant rats. ly with distilled water (control) and CTW at 10 g/kg (low dose) , 20 g/kg (medium dose), and 40 g/kg (high dose), respectively, twice a day for 2 weeks. Then we killed the rats, measured the levels of testosterone (T), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in the serum, obtained the testis weight, body weight, testis visceral coefficient and sperm concentration, and detected sperm viability, sperm motility and the level of cyclic adenosine monophosphate (cAMP) in the Leydig cells, followed by RESULTS: Compared with the control group, the low-dose, me-analysis of differences among different groups using the SPSS software. Medium-dose and high-dose CTW groups showed significant decreases in the serum T level ([3.09 +/-0.42] vs [1.22 +/-0. 32] , [1.06 +/- 0.29] and [0.57 +/-0.18] nmol/L, P<0.01), testis weight ([1.40 +/-0.16] vs [0.96 +/-0.09], [0.92 +/-0.11] and [0.91 +/- 0.08] g, P <0.01), and sperm concentration ([1.03 +/-0.16] vs [0.19 +/-0.07], [0.17 +/-0.08] and [0.16 +/-0.07] x 10(6)/ml, P <0.01), but a dramatic elevation in the testis visceral coefficient ([42.22 +/- 3.02] vs [51.39 +/- 3.09], [52.28 +/- 4.86] and [54.13 +/-6.06] mg/10 g, P <0.01); the medium- and high-dose CTW groups exhibited remarkable increases in the levels of serum LH ([13.62+/-0.89] vs [14.69 +/-0.12] and [14.93 +/-0.28] ng/L, P<0.01) and FSH ([4.32 +/-0.18] vs [4.77 +/-0.23] and [4.89 +/-0. 38] IU/L, P <0.05); all the three CTW groups showed markedly inhibited serum T secretion ([1.85 +/- 0.18] vs [1.42 +/-0.15], [1.12+/-0.18] and [0.88 +/-0.21] nmol/L, P<0.01) and intracellular cAMP ([5.51 +/-0.12] vs [4.39+/-0.06], [4.28 +/-0.07] and [4.11 +/- 0.10] nmol/L, P <0.01) in the Leydig cells. CONCLUSION: The water extract from CTW may reduce the synthesis of testosterone in the serum of male infant rats through the PKA pathway and consequently inhibit their testicular development and sperm production and affect the development of their reproductive system.
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Codonopsis/química , Extratos Vegetais/farmacologia , Sistema Urogenital/efeitos dos fármacos , Animais , AMP Cíclico/metabolismo , Células Intersticiais do Testículo/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Testosterona/sangueRESUMO
BACKGROUND: We present a case of an EWSR1/FUS::NFATC2 rearranged sarcoma in the left forearm and analyze its clinicopathological and molecular features. CASE SUMMARY: The patient is a 23-year-old woman. Microscopically, the tumor cells were medium-sized round cells arranged in small nests. The cytoplasm was clear, nuclei were relatively uniform, chromatin was dense, nucleoli were visible, and mitotic figures were rare. Immunohistochemically, the tumor cells were positive for Vimentin, INI-1, CD99, NKX2.2, CyclinD1, friend leukaemia virus integration 1, and NKX3.1. Next-generation sequencing revealed the presence of the EWSR1-NFATC2 fusion gene. EWSR1/FUS::NFATC2 rearranged sarcomas are rare and can easily be misdiagnosed. CONCLUSION: Clinical imaging, immunohistochemistry, and molecular pathology should be considered to confirm the diagnosis.
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There is a great demand for long-term cellular tracers because of their great importance in monitoring biological processes, pathological pathways, therapeutic effects, etc. Herein we report a new type of fluorescence "turn-on" probe for tracing live cells over a long period of time. We synthesized the fluorogenic probe by attaching a large number of tetraphenylethene (TPE) labels to a chitosan (CS) chain. The resultant TPE-CS bioconjugate shows a unique aggregation-induced emission (AIE) behavior. It is nonfluorescent when dissolved but becomes highly emissive when its molecules are aggregated. The AIE aggregates can be readily internalized by HeLa cells. The cellular staining by the TPE-CS aggregates is so indelible that it enables cell tracing for as long as 15 passages. The internalized AIE aggregates are kept inside the cellular compartments and do not contaminate other cell lines in the coculture systems, permitting the differentiation of specific cancerous cells from normal healthy cells.
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Acetileno/análogos & derivados , Técnicas Biossensoriais , Quitosana/química , Fluorescência , Corantes Fluorescentes/química , Acetileno/química , Corantes Fluorescentes/síntese química , Células HeLa , Humanos , Estrutura Molecular , Espectrometria de FluorescênciaRESUMO
MCL-1 is encoded by myeloid cell leukemia-1 gene (mcl-1), which is one of the anti-apoptotic members of bcl-2 cell apoptotic gene superfamily. ChanSu is made of dorsal secretions of several Bufo species, commonly used in the prescriptions of traditional Chinese medicine for treating many diseases including cancer. To clarify if mcl-1 is expressed in the dorsal skin of B. gargarizans, the PCR (polymerase chain reaction) was performed with its dorsal skin first strand cDNA as the template and a pair of specific primers of mcl-1, and PCR products were cloned into the pGM-T vector. DNA sequencing indicated that the ORF length was 639 bp encoding 212 amino acid residues, and the homology of 44%-95% with the MCL-1 of several other animals. For the further studies on MCL-1 biological functions during the oncogenesis and preparation of its antibody, the prokaryotic expression construct of pET-28b-mcl-1 was prepared which was confirmed by DNA sequencing, and its recombinant protein expression (0.02% wet weight) in E. coli BL21 (DE3) strain was confirmed by SDS-PAGE and Western blotting.
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Bufonidae/genética , Escherichia coli/metabolismo , Proteína de Sequência 1 de Leucemia de Células Mieloides/genética , Proteínas Recombinantes/metabolismo , Sequência de Aminoácidos , Animais , Bufonidae/classificação , Clonagem Molecular , DNA Complementar/genética , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Fases de Leitura Aberta/genética , Filogenia , Proteínas Recombinantes/genética , Alinhamento de Sequência , Homologia de Sequência , Pele/metabolismoRESUMO
Routine wound management faces significant challenges including rebleeding and bacterial infection that affect millions of people each year. However, conventional wound dressings (e.g., gauze, bandage) are limited to simply cover the injured surfaces and rarely show special functionality to promote the wound recovery. Currently, injectable hydrogels have been widely designed as multifunctional wound dressings to manage the hemostatic and wound healing process. Nevertheless, the integration of multiple functions through simple composition and easy construction is still difficult and hardly achieved. Herein, we reported a bioinspired multifunctional injectable hydrogel (CQCS@gel) consisted of only two components, catechol-functionalized quaternized chitosan (CQCS) and dibenzaldehyde-terminated poly(ethylene glycol) (DB-PEG2000). The building blocks endowed CQCS@gel with tissue-adhesive, antibacterial, antioxidant, self-healing and pH-responsive properties. Based on the in vivo hemostatic study, quick hemostasis for acute tissue injuries such as liver and carotid wounds was realized owing to the rapid gelation rate and strong tissue-adhesiveness of CQCS@gel. Moreover, CQCS@gel remarkably boosted the chronic recovery process of MRSA-infected cutaneous wounds by promoting collagen deposition, hair follicles regeneration and angiogenesis. Overall, this multifunctional injectable hydrogel shows potentials as a universal wound dressing in clinical applications, enabling both hemostasis and infected wound management. STATEMENT OF SIGNIFICANCE: This is the first report showing the multifunctional injectable hydrogel (CQCS@gel) consisted of catechol-functionalized quaternized chitosan and dibenzaldehyde-terminated poly(ethylene glycol). The incorporation of quaternary ammonium groups imparted the CQCS@gel with outstanding contact-active bacterial killing efficiency and the catechol moieties enhanced its tissue adhesive and antioxidant properties. Moreover, the reversible imine crosslinks endowed the CQCS@gel with self-healing and pH-responsive drug release capabilities. These multiple functions were integrated into a single injectable hydrogel system with easy availability and low cost. In vitro and in vivo results showed that the newly designed hydrogel was biocompatible, realized successful sealing hemostasis under multiple bleeding scenarios and enabled accelerated healing of infected skin wounds.
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Quitosana , Hemostáticos , Adesivos Teciduais , Humanos , Hidrogéis/farmacologia , Quitosana/farmacologia , Antioxidantes/farmacologia , Hemostasia , Hemostáticos/farmacologia , Adesivos Teciduais/farmacologia , Catecóis/farmacologia , Polietilenoglicóis/farmacologia , Antibacterianos/farmacologiaRESUMO
AIMS: Although there are many clinical reports on Dieulafoy's disease, there are few studies on the pathological structure of vascular wall in Dieulafoy's disease. METHODS: In this study, the main structural changes of the intima and media of the vascular wall were observed by special staining and immunohistochemical methods in the subjects of Dieulafoy's disease of stomach and intestine. RESULTS: There were many vessels of different sizes in the submucosa, with uneven wall thickness of the vessels. Compared with the normal control group, the content of blue collagen fibers between the vascular smooth muscle cells in the lesion group was increased, the elastic fibers were thickened, and the internal elastic plate was arranged stiff or even interrupted. CONCLUSIONS: The increase of collagen and elastic fibers between the smooth muscle cells of the medium membrane and the destruction of the structure of the inner elastic plate may be the structural basis of vascular lesions leading to Dieulafoy's disease.
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Miócitos de Músculo Liso , Estômago , Humanos , Coloração e RotulagemRESUMO
Diagnostic and therapeutic illumination on internal organs and tissues with high controllability and adaptability in terms of spectrum, area, depth, and intensity remains a major challenge. Here, we present a flexible, biodegradable photonic device called iCarP with a micrometer scale air gap between a refractive polyester patch and the embedded removable tapered optical fiber. ICarP combines the advantages of light diffraction by the tapered optical fiber, dual refractions in the air gap, and reflection inside the patch to obtain a bulb-like illumination, guiding light towards target tissue. We show that iCarP achieves large area, high intensity, wide spectrum, continuous or pulsatile, deeply penetrating illumination without puncturing the target tissues and demonstrate that it supports phototherapies with different photosensitizers. We find that the photonic device is compatible with thoracoscopy-based minimally invasive implantation onto beating hearts. These initial results show that iCarP could be a safe, precise and widely applicable device suitable for internal organs and tissue illumination and associated diagnosis and therapy.
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Óptica e Fotônica , Fototerapia , Fibras Ópticas , Fármacos Fotossensibilizantes , Desenho de EquipamentoRESUMO
Bacterial infections occur frequently during the implantation of medical devices, and functional coating is one of the effective means to prevent and remove biofilms. In this study, three different hydrophilic polyoxazolines with carboxyl groups (aPOx: PT1, PT2 and PT3) and bactericidal silver nanoparticles (AgNPs) were synthesized successfully, and an aPOx-AgNP multilayer film was prepared by electrostatic layer-by-layer self-assembly. The effect of charge density and assembly solution concentration was explored, and the optimal self-assembly parameters were established (PT2 1 mg/mL and AgNPs 3 mg/mL). The hydrophilicity of the surface can be enhanced to resist protein adhesion if the outermost layer is aPOx, and AgNPs can be loaded to kill bacteria, thereby realizing the bactericidal anti-adhesion potential integration of the aPOx-AgNP multilayer film. In addition, the aPOx-AgNP multilayer film was found to have the characteristic of intelligent and efficient pH-responsive silver release, which is expected to be used as a targeted anti-biofilm surface of implantable medical devices.
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Cyclodextrin-modified polycations have been studied widely due to their low cytotoxicity, low immunogenicity and the ability to form inclusion complexes. However, the influence of CD modification on cellular uptake and transfection efficiency of polyplexes is still unclear. In this research, cyclodextrin-modified polyethylenimines (PEI-CD) with different CD-grafting levels were synthesized, which were named PEI-CD(15) and PEI-CD(41), respectively, according to the CD number per PEI chain. CD modification showed great influence on the DNA condensation ability of the polycation. PEI-CD(15) could protect DNA completely above N/P ratio of 2. The particle sizes of these polyplexes were about 120 nm. However, PEI-CD(41) could not protect DNA below N/P of 6, and PEI-CD(41)/DNA polyplexes were larger than 1 µm, even at N/P ratio of 10. Therefore, this research was mainly focused on PEI-CD(15). It was interesting that the PEI-CD(15)/DNA polyplexes at N/P ratio of 8 and 10 displayed excellent stability in physiological salt conditions, probably due to the hydration shell of CDs. The influence of CD modification on the cellular uptake and transfection efficiency of polyplexes depended on the type of the cells. Uptake inhibition experiments indicated that PEI/DNA polyplexes were internalized by HEK293T cells by both clathrin-mediated endocytosis and caveolae-mediated endocytosis. The route of caveolae-mediated endocytosis was significantly promoted after CD modification. So the cell uptake and transfection efficiency of PEI-CD(15)/DNA polyplexes were significantly improved for HEK293T cells. However, the uptake and transfection efficiency of PEI-CD(15)/DNA polyplexes in HepG2 cells was similar to that of PEI/DNA polyplexes, probably due to the lack of endogenous caveolins.
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Ciclodextrinas/química , DNA/química , Técnicas de Transferência de Genes , Conformação de Ácido Nucleico/efeitos dos fármacos , Poliaminas/síntese química , Polietilenoimina/química , Cavéolas/metabolismo , Clatrina/metabolismo , Ciclodextrinas/metabolismo , Ciclodextrinas/farmacologia , Endocitose/efeitos dos fármacos , Citometria de Fluxo , Células HEK293 , Células Hep G2 , Humanos , Espectroscopia de Ressonância Magnética , Microscopia Eletrônica de Transmissão , Especificidade de Órgãos , Tamanho da Partícula , Plasmídeos/genética , Plasmídeos/metabolismo , Poliaminas/metabolismo , Poliaminas/farmacologia , Polieletrólitos , Polietilenoimina/metabolismo , Polietilenoimina/farmacologiaRESUMO
Emergent and long-term hemorrhage control is requisite and beneficial for reducing global mortality and postoperative complications (e.g., second bleeding and adverse tissue adhesion). Despite recent advance in injectable hydrogels for hemostasis, achieving rapid gelation, strong tissue-adhesive property and stable mechanical strength under fluid physiological environment is still challenging. Herein, we developed a novel chitosan hydrogel (CCS@gel) via dynamic Schiff base reaction and mussel-inspired catechol chemistry. The hydrogel possessed high gelation rate (<10 s), strong wet adhesiveness, excellent self-healing performance and biocompatibility. More importantly, the CCS@gel exhibited saline-induced contractile performance and mechanical enhancement, promoting its mechanical property in moist internal conditions. In vivo studies demonstrated its superior hemostatic efficacy for diverse anticoagulated visceral and carotid bleeding scenarios, compared to commercialized fibrin glue. The hydrogel-treated rats survived for 8 weeks with minimal inflammation and postoperative adhesion. These results revealed that the promising CCS@gel would be a facile, efficient and safe sealant for clinical hemorrhage control.
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Quitosana/farmacologia , Hemorragia/terapia , Hemostáticos/farmacologia , Hidrogéis/farmacologia , Adesivos Teciduais/farmacologia , Cicatrização/efeitos dos fármacos , Adesividade , Animais , Bandagens , Lesões das Artérias Carótidas/terapia , Quitosana/síntese química , Técnicas Hemostáticas/instrumentação , Hemostáticos/síntese química , Hidrogéis/síntese química , Fígado/lesões , Masculino , Polietilenoglicóis/síntese química , Polietilenoglicóis/farmacologia , Ratos Sprague-Dawley , Bases de Schiff/síntese química , Bases de Schiff/farmacologia , Baço/lesões , Adesivos Teciduais/síntese química , Técnicas de Fechamento de Ferimentos/instrumentaçãoRESUMO
For conductive hydrogels applied in biosensors, wearable devices and so forth, multifunctionality is an inevitable trend of development to meet various practical requirements and enhance human experience. Herein, inspired by nanocomposite, double-network (DN) and mussel chemistry, a new Graphene oxide@Dopamine/Alginate/Poly(acrylic acid-co-acrylamide) [GO@DA/Alginate/P(AAc-co-AAm)] hydrogel was fabricated through one-pot in-situ radical copolymerization. GO@DA nanofillers, prepared via GO confined DA polymerization, imparted the hydrogel with remarkable adhesiveness. Alginate/P(AAc-co-AAm) DN matrix, physically and chemically crosslinked by Fe3+ and N,N'-Methylenebisacrylamide, made hydrogels ultrastretchable, self-healing and biocompatible. With contents of DA and alginate accurately regulated, the tensile strength, elongation, adhesion strength and conductivity of the optimal hydrogel could reach 320.2 kPa, 1198 %, 36.9 kPa and 3.24 ± 0.12 S/m, respectively. What's more notable was that the synergistic integration of repeatable adhesiveness, strain sensitivity, use stability, self-healing ability and biocompatibility provided such hydrogels with tremendous possibility of practical application for strain sensors.
Assuntos
Acrilamidas/química , Adesivos/química , Alginatos/química , Bivalves/química , Dopamina/química , Grafite/química , Hidrogéis/química , Nanogéis/química , Adesividade , Animais , Materiais Biocompatíveis/química , Técnicas Biossensoriais , Sobrevivência Celular/efeitos dos fármacos , Condutividade Elétrica , Humanos , Camundongos , Células NIH 3T3 , Testes do Emplastro , Polimerização , Resistência à TraçãoRESUMO
Carbohydrate response element binding protein (ChREBP) is a glucose-sensing transcription factor that mediates the induction of glycolytic and lipogenic genes in response to glucose. We investigated the expression patterns of ChREBP and glucose transporters (GLUTs) in human hepatocellular carcinoma (HCC) and their association with HCC progression. ChREBP, GLUT2 and GLUT1 immunohistochemistry were performed on liver tissue array containing normal liver tissue, HCC adjacent tissue and cancer tissue of different HCC stages. The effect of HCC malignancy on protein expression was analyzed with one-way ANOVA. The correlations between protein expressions were analyzed with Pearson Correlation test. We found that ChREBP protein expression tended to be positively correlated to liver malignancy. GLUT2 protein expression was significantly reduced in human HCC as compared to normal liver tissue and its expression in HCC was inversely associated to malignancy (p < 0.001). In contrast, GLUT1 was significantly increased in cancer cells and its expression was positively correlated to malignancy (p < 0.001). Furthermore, GLUT1 expression was positively associated to ChREBP expression (r = 0.481, p < 0.0001, n = 70) but negatively correlated to GLUT2 expression (r = -0.320, p = 0.007, n = 70). Notably, ChREBP-expressing hepatocytes did not express GLUT2 but GLUT1. This is the first report unveiling expressions of ChREBP and GLUT2/GLUT1 and their relations in HCC. The expression patterns are related to malignancy and this information would facilitate evaluation of clinical behavior and treatment of HCC.