RESUMO
Hydrogels composed of natural polysaccharides have been widely used as filling materials, with a growing interest in medical cosmetology and skin care. However, conventional commercial dermal fillers still have limitations, particularly in terms of mechanical performance and durability in vivo. In this study, a novel injectable and implantable hydrogel with adjustable characteristics was prepared from succinoglycan riclin by introducing PEG diglycidyl ether as a cross-linker. FTIR spectra confirmed the cross-linking reaction. The riclin hydrogels exhibited shear-thinning behavior, excellent mechanical properties, and cytocompatibility through in vitro experiments. Furthermore, when compared with subcutaneous injection of a commercial hyaluronic acid hydrogel, the riclin hydrogels showed enhanced persistence and biocompatibility in Balb/c mice after 16 weeks. These results demonstrate the great potential of the riclin-based hydrogel as an alternative to conventional commercial soft tissue fillers.
Assuntos
Hidrogéis , Engenharia Tecidual , Animais , Camundongos , Injeções Subcutâneas , Ácido Hialurônico , Excipientes , Camundongos Endogâmicos BALB C , Polietilenoglicóis , ÉteresRESUMO
Postoperative peritoneal adhesions are a prevalent clinical issue following abdominal and pelvic surgery, frequently resulting in heightened personal and societal health burdens. Traditional biomedical barriers offer limited benefits because of practical challenges for doctors and their incompatibility with laparoscopic surgery. Hydrogel materials, represented by hyaluronic acid gels, are receiving increasing attention. However, existing antiadhesive gels still have limited effectiveness or carry the risk of complications in clinical applications. Herein, we developed a novel hydrogel using polysaccharide hemoadhican (HD) as the base material and polyethylene glycol diglycidyl ether (PEGDE) as the cross-linking agent. The HD hydrogels exhibit appropriate mechanical properties, injectability, and excellent cytocompatibility. We demonstrate resistance to protein adsorption and L929 fibroblast cell adhesion to the HD hydrogel. The biodegradability and efficacy against peritoneal adhesion are further evaluated in C57BL/6 mice. Our results suggest a potential strategy for anti-postoperative tissue adhesion barrier biomaterials.
Assuntos
Implantes Absorvíveis , Hidrogéis , Ratos , Camundongos , Animais , Hidrogéis/farmacologia , Ratos Sprague-Dawley , Aderências Teciduais/prevenção & controle , Camundongos Endogâmicos C57BL , Complicações Pós-Operatórias/prevenção & controleRESUMO
TRIP4 is a conserved transcriptional coactivator that is involved in the regulation of the expression of multiple genes. It consists of a classical N-terminal C2HC5-like zinc-finger domain and a conserved C-terminal ASCH domain. Here, we characterized the DNA-binding properties of the human TRIP4 ASCH domain. Our biochemical data show that TRIP4-ASCH has comparable binding affinities toward ssDNA and dsDNA of different lengths, sequences, and structures. The crystal structures reveal that TRIP4-ASCH binds to DNA substrates in a sequence-independent manner through two adjacent positively charged surface patches: one binds to the 5'-end of DNA, and the other binds to the 3'-end of DNA. Further mutagenesis experiments and binding assays confirm the functional roles of key residues involved in DNA binding. In summary, our data demonstrate that TRIP4-ASCH binds to the 5' and 3'-ends of DNA in a sequence-independent manner, which will facilitate further studies of the biological function of TRIP4.
Assuntos
Proteínas de Ligação a DNA , DNA , Modelos Moleculares , Ligação Proteica , Fatores de Transcrição , Humanos , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/química , Cristalografia por Raios X , Sítios de Ligação , DNA/metabolismo , DNA/química , DNA de Cadeia Simples/metabolismo , DNA de Cadeia Simples/química , Domínios Proteicos , Sequência de Aminoácidos , Dedos de Zinco , Proteínas RepressorasRESUMO
Uncontrolled hemorrhage is a leading cause of death, emphasizing the need for novel hemostatic agents. Here, a novel hemostatic polysaccharide hemoadhican (HD) is screened out by analyzing the rheological properties of screened material mixed blood sludges, which is prepared by mixing polysaccharide granules and whole blood to mimic the coagulation in vitro. HD is produced by a bacterial isolate Paenibacillus sp.1229, and the repeating units of HD are â)-α-L-Rhap-(1â3)-ß-D-Glcp-(1â4)[4,6-ethylidene-α-D-Galp-(1â4)-α-D-Glcp-(1â3)]-α-D-Manp-(1â. Compared to chitosan and celox, HD achieves more effective hemostasis in animal models with mouse and rat femoral arteries, rat carotid arteries, and rabbit femoral arteries. Especially, HD maintains an excellent hemostatic capability in animals with heparin-induced hemorrhage diathesis. In vitro experiments show HD granules can quickly absorb a small amount of blood component to create a hemophobic blood sludge resistant to high pressure. The blood sludge firmly adheres to damaged tissue and efficiently repels blood. In vitro experiments show that HD does not actively trigger blood coagulation cascade and is independent of blood conditions including heparin treatment. In addition, HD moisturizes wounds and accelerates wound healing, exhibiting excellent biodegradability, and hemocompatibility. The results indicate that HD is a promising hemostatic material for treating traumatic hemorrhages and uncontrollable surgical bleeding.
Assuntos
Quitosana , Hemostáticos , Ratos , Camundongos , Animais , Coelhos , Hemostáticos/farmacologia , Esgotos , Aderências Teciduais , Coagulação Sanguínea , Hemostasia , Hemorragia/tratamento farmacológico , Polissacarídeos , Heparina/farmacologiaRESUMO
In the present study, we determined the vascular functions using a canine model of isolated intestinal segment perfused with constant flow. The effects of an NO donor, S-nitroso-N-acetylpenicillamine (SNAP) and an NO synthase inhibitor, N(omega)-nitro-l-arginine methyl ester (l-NAME) on the vascular factors (resistance, exchange and capacitance) were evaluated. In condition of venous pressure at 0 mmHg, we determined and calculated arterial pressure (Pa) and capillary pressure (Pc). Vascular factors including total, pre- and post-capillary resistance (R(T), Ra and Rv), vascular compliance (VC) and capillary filtration coefficient (K(fc)) were obtained. SNAP at doses 10(-6) to 10(-4) mol/l produced vasodilatory effects. It dose-dependently reduced the Pa, Pc, R(T) and Ra, as well as the Ra/Rv ratio. The Rv was slightly decreased. This agent increased the vascular capacity, VC and K(fc). NO inhibition with l-NAME (10(-6) to 10(-4) mol/l) produced the opposite effects. The vasoconstrictory effects of l-NAME increased Pa, Pc, R(T) and Ra as well as the Ra/Rv ratio. It slightly raised the Rv. l-NAME reduced the vascular capacity, VC and K(fc). The effects of l-NAME were also dose-dependent. This study has provided a detailed data of the vasodilatory and vasoconstrictory effects NO donation and inhibition on vascular factors in the intestinal vasculature.
Assuntos
Permeabilidade Capilar/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Íleo/irrigação sanguínea , Doadores de Óxido Nítrico/farmacologia , Óxido Nítrico Sintase/antagonistas & inibidores , Resistência Vascular/efeitos dos fármacos , Vasoconstritores/farmacologia , Vasodilatadores/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Capilares/efeitos dos fármacos , Capilares/enzimologia , Cães , Relação Dose-Resposta a Droga , Capacitância Elétrica , Técnicas In Vitro , Artérias Mesentéricas/efeitos dos fármacos , Artérias Mesentéricas/enzimologia , Veias Mesentéricas/efeitos dos fármacos , Veias Mesentéricas/enzimologia , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase/metabolismo , Perfusão , S-Nitroso-N-Acetilpenicilamina/farmacologia , Fatores de Tempo , Vasoconstrição/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Pressão Venosa/efeitos dos fármacosRESUMO
In the present study, we elucidated the possible role of hemodynamic parameters and chemical factors in the development of ventricular hypertrophy (VH) following chronic nitric oxide (NO) deprivation with Nomega-nitro-L-arginine methyl ester (L-NAME). Impedance spectral analysis was used to obtain the arterial hemodynamics including the steady and pulsatile components. Body weight (BW), left ventricular (LV) weight (LVW), LVW/BW ratio, LV collagen volume fraction (LVCVF), cyclic GMP, and nitrite/nitrate were measured. The extent of VH was evaluated by the LW/BW, total number, numerical density, and size of cardiomyocytes. Sprague-Dawley rats were given L-NAME 10, 20, and 40 mg/kg/day from the age of 10 to 18 weeks. Control and age-matched rats were given vehicle for the same period. Treatment of L-NAME for 8 weeks caused a dose-dependent increase in tail cuff pressure and a reduction in BW with increases in LVW, LVW/BW, number, numerical density, and size of myocytes. There was elevation of aortic pressure with decreases in cardiac output, and arterial compliance. The total peripheral resistance, characteristic impedance and pulse wave reflection were increased. Histological finding revealed severe myocardial hypertrophy and fibrosis with fibroblast infiltration. The LVCVF was increased, while LV cGMP and nitrite/nitrate were reduced in a dose-dependent manner. The results suggest that chronic NOS blockade causes hypertension, impairment of large vessel properties, and VH. The development of VH may result partly from the decreases in cGMP and nitrite/nitrate in the ventricle. Correlation analysis indicates that the extent of VH is equally related to the steady and pulsatile hemodynamics.
Assuntos
Artérias/fisiopatologia , Cardiomegalia/fisiopatologia , Hemodinâmica/fisiologia , Óxido Nítrico/fisiologia , Algoritmos , Animais , Peso Corporal/efeitos dos fármacos , Cardiomegalia/patologia , Contagem de Células , Colágeno/metabolismo , GMP Cíclico/metabolismo , Eletrocardiografia/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , NG-Nitroarginina Metil Éster/farmacologia , Nitratos/metabolismo , Óxido Nítrico Sintase Tipo III/antagonistas & inibidores , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Função Ventricular Esquerda/efeitos dos fármacos , Função Ventricular Esquerda/fisiologiaRESUMO
1. The effects of ovariectomy (Ovx), menopause and oestrogen replacement on the haemodynamics remain controversial. The present study employed the technique of arterial impedance analysis to measure and calculate the steady and pulsatile haemodynamics. The purpose was to determine the haemodynamic consequence of ovariectomy and oestrogen replacement. 2. Ovariectomy was carried out under anaesthesia on female Sprague Dawley rats aged 9 weeks. Oestrogen (17 beta-estradiol or E(2)) replacement started 1 week after ovariectomy for 4 weeks. Ovx increased the body weight (BW), while it greatly reduced the uterus weight. Left ventricular weight (LVW) was slightly increased, but LVW/BW ratio was slightly reduced. These changes were reversed after E(2) replacement. 3. Compared to sham group, Ovx with or without E(2) replacement did not significantly affect the systolic, mean and diastolic pressure. In Ovx, pulse pressure (PP) and heart rate were significantly increased, while stroke volume and cardiac output were slightly decreased. Total peripheral resistance (TPR) was largely elevated, indicating Ovx induced systemic vasoconstriction. These changes all returned to close normal values (sham group) after E(2) replacement, except PP. 4. Ovx increased the characteristic input impedance (Zc) and pulse wave reflection, while it decreased arterial compliance. E(2) treatment reversed these changes, except Zc. 5. These results demonstrate that Ovx influences both the resistance and Windkessel functions of the artery. E(2) treatment effectively reverses most the effects of Ovx both on the steady and pulsatile haemodynamics.
Assuntos
Estradiol/farmacologia , Hemodinâmica/efeitos dos fármacos , Hemodinâmica/fisiologia , Animais , Artérias , Pressão Sanguínea/efeitos dos fármacos , Débito Cardíaco/efeitos dos fármacos , Complacência (Medida de Distensibilidade) , Impedância Elétrica , Estradiol/sangue , Terapia de Reposição de Estrogênios , Feminino , Ovariectomia , Fluxo Pulsátil/efeitos dos fármacos , Fluxo Pulsátil/fisiologia , Radioimunoensaio , Ratos , Ratos Sprague-Dawley , Volume Sistólico , Resistência Vascular/efeitos dos fármacosRESUMO
Aortic stiffness (AS) exerts significant impact on the cardiovascular risks. We developed a new model to produce AS. The purposes were to evaluate the haemodynamic consequence and to correlate the haemodynamic parameters with the extent of ventricular hypertrophy (VH). We applied silicon gel for embedding of the abdominal and/or thoracic aorta. After 1-4 weeks of AS, the left ventricular weight (LVW), LVW to body weight (BW) ratio (LVW/BW), and the morphological changes in cardiomyotes were quantified for VH. We determined the aortic pressure (AP), stroke volume, cardiac output, total peripheral resistance (TPR), characteristic impedance (Zc), pulse wave reflection (P(b)) and pulse wave velocity (PWV). Aortic embedding (AE) increased LVW, LVW/BW, systolic and pulse pressure (PP), Zc, P(b) and PWV accompanied by decreases in diastolic pressure and arterial compliance. The magnitude of these haemodynamic and cardiac changes were in an order of combined, thoracic and abdominal AE. Correlation analysis revealed that the VH was well correlated with pulsatile haemodynamics such as Zc, PP, P(b) and PWV, while less with steady components (Mean AP and TPR). Our results indicate that pulsatile haemodynamic parameters are significantly elevated after AS. The alterations in pulsatile haemodynamics are the major causes leading to VH.