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Gelatin-based bioadhesives, especially methacrylated gelatin (GelMA), have emerged as superior alternatives to sutureless wound closure. Nowadays, their mechanical improvement and therapeutic delivery, particularly for hydrophobic antibiotics, have received ever-increasing interest. Herein, a reinforced gelatin-based hydrogel with a hydrophobic drug delivery property for skin wound treatment was reported. First, photosensitive monomers of N'-(2-nitrobenzyl)-N-acryloyl glycinamide (NBNAGA) were grafted onto GelMA via Michael addition, namely, GelMA-NBNAGA. Second, gelation of the GelMA-NBNAGA solution was accomplished in a few seconds under one step of ultraviolet (UV) light irradiation. Multiple effects were realized simultaneously, including chemical cross-linking initiated by lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP), physical cross-linking of uncaged dual hydrogen bonding, and hydrophobic drug release along with o-NB group disintegration. The mechanical properties of the dual-reinforcement hydrogels were verified to be superior to those only with a chemical or physical single-cross-linked network. The hydrophobic anticancer doxorubicin (DOX) and antibiotic rifampicin (Rif) were successfully charged into the hydrogels, separately. The in vitro antimicrobial tests confirmed the antibacterial activity of the hydrogels against Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria. The in vivo wound-healing assessment in mice further assured their drug release and efficacy. Therefore, this NBNAGA-modified GelMA hydrogel has potential as a material in skin wound dressing with a hydrophobic antibiotic on-demand delivery.
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Starter cultures play a significant role in lipid hydrolysis, prevention of lipid oxidation, and synthesis of fatty acid in fermented sausage, enhancing product quality. In this study, five synergistic bacterial strains were used, including Pediococcus pentosaceus (B-3), Latilactobacillus sakei DLS-24 (D-24), Latilactobacillus acidophilus DLS-29 (D-29), Lactiplantibacillus pentosus (B-1), and Lactiplantibacillus plantarum (B-2). Sausage B1B3D24 gave the highest free fatty acid with 39.45 g/100 g at 45-Day. Based on 2-thiobarbituric acid reactive substance, B2B3 contains 112.68 MDA/kg. Lipoxygenase activity displays the lowest in B1B3D24 with 0.095 µmol/min·mg followed by B2B3 with 0.145 µmol/min·mg. B1B3D24 contains 11.35 g/kg of monounsaturated fatty acid with the highest content in eicosenoic acid (C20:1) and palmitoleic acid (C16:1). The fatty acid synthesis pathway in B1B3D24 contains an active positive interaction with PUFA to increase the isotopomers of ω-3 and ω-6 fatty acids. In addition, lipid mediating genes in B1B3D24 show the highest counts in fatty-acid synthase, carbonyl reductase 4, 3-oxoacyl-[acyl-carrier-protein] synthase III, hydroxysteroid 17-beta dehydrogenase 8, and acetyl-CoA carboxylase.
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Ácidos Grasos , Fermentación , Productos de la Carne , Oxidación-Reducción , Productos de la Carne/análisis , Productos de la Carne/microbiología , Ácidos Grasos/metabolismo , Ácidos Grasos/química , Animales , Porcinos , Hidrólisis , Pediococcus pentosaceus/metabolismo , Pediococcus pentosaceus/genética , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Metabolismo de los LípidosRESUMEN
Particulate matter (PM) induces and enhances oxidative stress and inflammation, leading to a variety of respiratory diseases, including acute lung injury. Exploring new treatments for PM-induced lung injury has long been of interest to researchers. Palmatine (PAL) is a natural extract derived from plants that has been reported in many studies to alleviate inflammatory diseases. Our study was designed to explore whether PAL can alleviate acute lung injury caused by PM. The acute lung injury model was established by instilling PM (4 mg/kg) into the airway of mice, and PAL (50 mg/kg and 100 m/kg) was administrated orally as the treatment groups. The effect and mechanism of PAL treatment were examined by immunofluorescence, immunohistochemistry, Western Blotting, ELISA, and other experiments. The results showed that oral administration of PAL (50 mg/kg and 100 m/kg) could significantly alleviate lung inflammation and acute lung injury caused by PM. In terms of mechanism, we found that PAL (50 mg/kg) exerts anti-inflammatory and anti-damage effects mainly by enhancing the activation of the Nrf2-related antioxidant pathway and inhibiting the activation of the NLRP3-related pyroptosis pathway in mice. These mechanisms have also been verified in our cell experiments. Further cell experiments showed that PAL may reduce intracellular reactive oxygen species (ROS) by activating Nrf2-related pathways, thereby inhibiting the activation of NLRP3-related pyroptosis pathway induced by PM in Beas-2B cell. Our study suggests that PAL can be a new option for PM-induced acute lung injury.
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Phenotype transformation of vascular smooth muscle cells (VSMCs) plays an important role in the development of atherosclerosis. Asprosin is a newly discovered adipokine, which is critical in regulating metabolism. However, the relationship between asprosin and phenotype transformation of VSMCs in atherosclerosis remains unclear. The aim of this study is to investigate whether asprosin affects the progression of atherosclerosis by inducing phenotype transformation of VSMCs. We established an atherosclerosis model in ApoE-/- mice and administered asprosin recombinant protein and asprosin antibody to mice. Knocking down asprosin was also as an intervention. Interestingly, we found a correlation between asprosin levels and atherosclerosis. Asprosin promoted plaque formation and phenotype transformation of VSMCs. While, AspKD or asprosin antibody reduced the plaque lesion and suppressed vascular stiffness in ApoE-/- mice. Mechanistically, asprosin induced phenotype transformation of MOVAs by binding to GPR54, leading to Gαq/11 recruitment and activation of the PLC-PKC-ERK1/2-STAT3 signaling pathway. Si GPR54 or GPR54 antagonist partially inhibited the action of asprosin in MOVAs. Mutant GPR54-(267, 307) residue cancelled the binding of asprosin and GPR54. In summary, this study confirmed asprosin activated GPR54/Gαq/11-dependent ERK1/2-STAT3 signaling pathway, thereby promoting VSMCs phenotype transformation and aggravating atherosclerosis, thus providing a new target for the treatment of atherosclerosis.
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Aterosclerosis , Músculo Liso Vascular , Miocitos del Músculo Liso , Fenotipo , Animales , Aterosclerosis/metabolismo , Aterosclerosis/patología , Aterosclerosis/genética , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patología , Ratones , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/patología , Fibrilina-1/metabolismo , Fibrilina-1/genética , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Masculino , Transducción de Señal , Modelos Animales de Enfermedad , Apolipoproteínas E/deficiencia , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Humanos , Proteínas de la Matriz Extracelular/metabolismo , Proteínas de la Matriz Extracelular/genética , Ratones NoqueadosRESUMEN
Polyelectrolyte-surfactant complexes (PESCs) have garnered significant attention due to their extensive range of biological and industrial applications. Most present applications are predominantly used in liquid or emulsion states, which limits their efficacy in solid material-based applications. Herein, pre-hydrolyzed polyacrylonitrile (HPAN) and quaternary ammonium salts (QAS) are employed to produce PESC electrospun membranes via electrospinning. The formation process of PESCs in a solution is observed. The results show that the degree of PAN hydrolysis and the varying alkyl chain lengths of surfactants affect the rate of PESC formation. Moreover, PESCs/PCL hybrid electrospun membranes are fabricated, and their antibacterial activities against both Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus) are investigated. The resulting electrospun membranes exhibit high bactericidal efficacy, which enables them to serve as candidates for future biomedical and filtration applications.
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Growth is a crucial economic trait of all aquaculture species. It is important to explore the molecular regulation on growth, which could help improve the growth rate of species. Mining the growth-related genes is the foundation for revealing its molecular regulation on growth. Presently, the molecular regulation of growth in Procambarus clarkii is not clear, and the study on exploring growth-related genes is limited. In this study, RNA-Seq was used to compare gene expression profiles of the individuals with different growth rates involved in four groups including Big Male (BM), Big Female (BF), Small male (SM), and Small Female (SF) from one P. clarkii family, and the analyses were performed in combination with sex. Meanwhile, whole-genome resequencing data was used to get growth-specific SNP (Single Nucleotide Polymorphism)/InDel (Insertion/Deletion) sites information. Totally, we identified 16,127 genes, of which 9065 were successfully annotated in the GO database. Among these, 1328 DEGs were identified in BM vs. SM, with 357 up-regulated and 971 down-regulated. Additionally, 3507 DEGs were identified in BF vs. SF, with 241 up-regulated and 3266 down-regulated. 96 DEGs were up-regulated and 820 DEGs were down-regulated in Growth-related Group. The expression levels of nine DEGs were validated by RT-qPCR to verify the analysis results of sequencing. 684,040 growth-related SNPs and 182,050 growth-related InDels were obtained after screened. These findings provide candidate growth-related genes and growth-specific SNP/InDel sites for regulation of growth traits in P. clarkii, and new insight into the molecular regulation of P. clarkii growth.
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Perfilación de la Expresión Génica , Transcriptoma , Humanos , Femenino , Masculino , Animales , Astacoidea/genética , Genoma , RNA-SeqRESUMEN
Restenosis after angioplasty is caused usually by neointima formation characterized by aberrant vascular smooth muscle cell (VSMC) dedifferentiation. Myeloid-derived growth factor (MYDGF), secreted from bone marrow-derived monocytes and macrophages, has been found to have cardioprotective effects. In this study we investigated the effect of MYDGF to postinjury neointimal formation and the underlying mechanisms. Rat carotid arteries balloon-injured model was established. We found that plasma MYDGF content and the level of MYDGF in injured arteries were significantly decreased after balloon injury. Local application of exogenous MYDGF (50 µg/mL) around the injured vessel during balloon injury markedly ameliorated the development of neointimal formation evidenced by relieving the narrow endovascular diameter, improving hemodynamics, and reducing collagen deposition. In addition, local application of MYDGF inhibited VSMC dedifferentiation, which was proved by reversing the elevated levels of osteopontin (OPN) protein and decreased levels of α-smooth muscle actin (α-SMA) in the left carotid arteries. We showed that PDGF-BB (30 ng/mL) stimulated VSMC proliferation, migration and dedifferentiation in vitro; pretreatment with MYDGF (50-200 ng/mL) concentration-dependently eliminated PDGF-BB-induced cell proliferation, migration and dedifferentiation. Molecular docking revealed that MYDGF had the potential to bind with sphingosine-1-phosphate receptor 2 (S1PR2), which was confirmed by SPR assay and Co-IP analysis. Pretreatment with CCG-1423 (Rho signaling inhibitor), JTE-013 (S1PR2 antagonist) or Ripasudil (ROCK inhibitor) circumvented the inhibitory effects of MYDGF on VSMC phenotypic switching through inhibiting S1PR2 or its downstream RhoA-actin monomers (G-actin) /actin filaments (F-actin)-MRTF-A signaling. In summary, this study proves that MYDGF relieves neointimal formation of carotid arteries in response to balloon injury in rats, and suppresses VSMC dedifferentiation induced by PDGF-BB via S1PR2-RhoA-G/F-actin-MRTF-A signaling pathway. In addition, our results provide evidence for cross talk between bone marrow and vasculature.
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Actinas , Neointima , Ratas , Animales , Becaplermina/farmacología , Neointima/tratamiento farmacológico , Neointima/metabolismo , Actinas/metabolismo , Ratas Sprague-Dawley , Receptores de Esfingosina-1-Fosfato/metabolismo , Factor Estimulante de Colonias de Granulocitos/metabolismo , Factor Estimulante de Colonias de Granulocitos/farmacología , Músculo Liso Vascular , Simulación del Acoplamiento Molecular , Proliferación Celular , Transducción de Señal , Movimiento Celular , Miocitos del Músculo Liso/metabolismo , Células CultivadasRESUMEN
There are several technical challenges and public issues concerning genome editing applications before they become viable in commercial aquaculture. Recently, we developed a novel strategy to generate all-female (AF) common carp, which exhibited a growth advantage over the control carp, using genetic editing through single gene-targeting manipulation. Here, we found that the body weight of the AF common carp was higher by 22.58% than that of the control common carp. Because the genotype of the AF common carp was cyp17a1+/-;XX, the contents of sex steroids were normally synthesized, as they were comparable to that of the control female carp. To evaluate the food safety of the AF carp, Wistar rats were fed a diet containing control female carp (control, C) or all-female (AF) carp at an incorporation rate of 5, 10 and 20% (w/w) for 90 days. Compared with those fed control carp, the rats fed AF common carp exhibited no significant difference in body weight, food intake, feed conversion ratio, hematology, serum biochemistry, urine test, relative organ weight, gross necropsy, and histopathological examination. This is the first food safety assessment of the farmed fish strain cultured using CRISPR/Cas9, which will further advance the fishery development of genome-edited animals.
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Carpas , Edición Génica , Femenino , Animales , Ratas , Ratas Wistar , Genotipo , Peso Corporal , Alimentación Animal/análisis , DietaRESUMEN
INTRODUCTION: There were controversial opinions on the use of bivalirudin versus heparin for anticoagulant therapy in extracorporeal membrane oxygenation. The aim of our present study is to evaluate the efficacy and safety of bivalirudin versus heparin for the maintenance of systemic anticoagulation during adult veno-venous extracorporeal membrane oxygenation (V-V ECMO). METHODS: Adult patients who received V-V ECMO support in our center between February 2018and February 2022 were retrospectively recruited. We analyzed their ECMO support time, platelet count, coagulation indicators, blood product infusion volume, the incidence of thrombosis and bleeding, probability of successful weaning of ECMO, and in-hospital mortality. RESULTS: A total of 58 patients received V-V ECMO support. Thirty-four patients were finally included according to the exclusion and inclusion criteria, 14 and 20 accepted bivalirudin and heparin for anticoagulant therapy, respectively. The Minimum platelet value (98.50 × 109/L (85.50, 123.75) vs 49.50 × 109/L (31.25, 83.00), p = 0.002) and mean platelet value (149.90 × 109/L (127.40, 164.80) vs 74.55 × 109/L (62.45, 131.60), p = 0.03) and the ratio of successful weaning of ECMO (92.8% vs 60.0%, p = 0.033) in bivalirudin group were significantly higher than those in heparin group. The red blood cell infusion volume (7.00 U (3.00, 13.25) vs 13.75 U (7.25, 22.63), p = 0.039), platelet infusion volume (0.00 mL (0.00, 75.00) vs 300 mL (0.00, 825.00), p = 0.027), and the incidence of major bleeding (0.00% vs 30%, p = 0.024) in bivalirudin group were significantly lower than those in heparin group. CONCLUSIONS: In V-V ECMO-supported adult patients, systemic anticoagulation with bivalirudin has achieved the same anticoagulation targets as heparin with less frequency of major bleeding events and lower requirement for blood products without significantly increased risk of thrombosis. Bivalirudin most likely is a safe and effective anticoagulation method for adult patients supported by V-V ECMO.
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Oxigenación por Membrana Extracorpórea , Trombosis , Humanos , Adulto , Heparina/efectos adversos , Estudios Retrospectivos , Oxigenación por Membrana Extracorpórea/efectos adversos , Oxigenación por Membrana Extracorpórea/métodos , Estudios de Casos y Controles , Anticoagulantes/efectos adversos , Fragmentos de Péptidos/efectos adversos , Hemorragia/inducido químicamente , Trombosis/etiología , Trombosis/prevención & control , Fibrinolíticos , Proteínas Recombinantes/efectos adversosRESUMEN
BACKGROUND: Total knee arthroplasty (TKA) is known to be a painful orthopedic procedure and moderate to severe pain is common, especially immediately postoperatively and during active motion. The aim of the present study was to compare epidural analgesia (EA) and adductor canal block (ACB) techniques with regard to early period pain levels, need for additional opioids, and ambulation and functional scores in patients who had undergone primary TKA. METHODS: Approval for the study was granted by the Changji Branch of the First Affiliated Hospital of Xinjiang Medical University. Written informed consent will be obtained from all of the participants. Inclusion criteria included the following: planned unilateral TKA; spinal anesthesia; American Society of Anesthesiologists physical status classification score of I to III. Prospective assessment will be done for 100 patients who are scheduled for unilateral primary TKA surgery in our academic hospital by a single senior surgeon between August 2020 and December 2021. Patients were randomized to ACB treatment or EA treatment by a computer random number generator. The primary outcome was visual analog scale pain scores in the immediate postoperative period. Secondary outcomes included postoperative opioid use, length of hospital stay, activity level during physical therapy, and knee range of motion. Results were evaluated in a confidence interval of 95% and at a significance level of Pâ<â.05. CONCLUSIONS: We hypothesized that standard ACB would be as effective as EA for postoperative pain management following TKA. TRIAL REGISTRATION: This study protocol was registered in Research Registry (researchregistry5775).
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Analgesia Epidural , Artroplastia de Reemplazo de Rodilla/efectos adversos , Bloqueo Nervioso/métodos , Manejo del Dolor/métodos , Dolor Postoperatorio/prevención & control , Humanos , Articulación de la Rodilla/fisiopatología , Dimensión del Dolor , Dolor Postoperatorio/etiología , Rango del Movimiento ArticularRESUMEN
The secreted frizzled-related protein 1 (SFRP1) gene plays an important role in carcinogenesis of digestive system cancer. Previous studies proved that circulating DNA promoter methylation may be a suitable biomarker for cancer patients. The aim of the present study was to investigate whether the promoter methylation status of serum SFRP1 is a potential biomarker for gastric adenocarcinoma (GAC) and esophageal square cell carcinoma (ESCC). The blood samples obtained from 42 GAC and 36 ESCC patients were detected for the promoter methylation status of SFRP1 by methylation-specific polymerase chain reaction. The control group included 42 benign gastrointestinal disease volunteers (24 benign gastric disease and 18 benign esophageal disease) and 20 healthy volunteers. Serum SFRP1 methylation was evident in 30.95% (13/42) GAC patients and 38.89% (14/36) ESCC patients, which is clearly higher compared to 8.33% (2/24) in benign gastric disease, 11.11% (2/18) in benign esophageal disease and 5% (1/20) in healthy volunteers (P<0.05). The association between the serum SFRP1 promoter methylation status and the clinical pathological features were further analyzed and methylation of the SFRP1 gene was significantly associated with age >60 years in GAC patients (P=0.027). However, no correlations between the SFRP1 methylation status and other clinicopathological parameters were found. In conclusion, the SFRP1 promoter was detected frequently in the serum of GAC and ESCC patients. The detection of circulating methylated SFRP1 in the serum may be a useful biomarker for upper gastrointestinal cancer patients.
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Novel YVO(4):Eu(3+)/YBO(3) core/shell heteronanostructures with different shell ratios (SRs) were successfully prepared by a facile two-step method. X-ray diffraction, transmission electron microscopy and X-ray photoelectron spectroscopy were used to characterize the heteronanostructures. Photoluminescence (PL) study reveals that PL efficiency of the YVO(4):Eu(3+) nanocrystals (cores) can be improved by the growth of YBO(3) nanocoatings onto the cores to form the YVO(4):Eu(3+)/YBO(3) core/shell heteronanostructures. Furthermore, shell ratio plays a critical role in their PL efficiency. The heteronanostructures (SR = 1/7) exhibit the highest PL efficiency; its PL intensity of the (5)D(0)-(7)F(2) emission at 620 nm is 27% higher than that of the YVO(4):Eu(3+) nanocrystals under the same conditions.
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Porous zinc ferrite (ZnFe(2)O(4)) nanorods with a diameter of around 50 nm and a length of several micrometers have been synthesized by a microemulsion-based method in combination with calcination at 500 °C. The morphology and structure of the ZnFe(2)O(4) nanorods and its precursor (ZnFe(2)(C(2)O(4))(3) nanorods) were systematically characterized by x-ray powder diffraction, transmission electron microscopy, field emission scanning electron microscopy and high-resolution transmission electron microscopy. The formation mechanism for the porous ZnFe(2)O(4) nanorods is also discussed. Moreover, the porous ZnFe(2)O(4) nanorods were applied in a room-temperature ethanol sensor and exhibited much better sensing performance than ZnFe(2)O(4) nanoparticles.