RESUMEN
Nanoplastics are recognized as emerging contaminants that can cause severe toxicity to marine fishes. However, limited researches were focusing on the toxic effects of nanoplastics on marine fish, especially the post-exposure resilience. In this study, red drum (Sciaenops ocellatus) were exposed to 5â¯mg/L polystyrene nanoplastics (100â¯nm, PS-NPs) for a 7-day exposure experiment, and a 14-day recovery experiment that followed. The aim was to evaluate the dynamic alterations in hepatic and branchial tissue damage, hepatic antioxidant capacity, as well as hepatic transcriptional and metabolic regulation in the red drum during exposure and post-exposure to PS-NPs. Histopathological observation found that PS-NPs primarily triggered hepatic lipid droplets and branchial epithelial liftings, a phenomenon persistently discernible up to the 14 days of recovery. Although antioxidant capacity partially recovered during recovery periods, PS-NPs resulted in a sustained reduction in hepatic antioxidant activity, causing oxidative damage throughout the entire exposure and recovery phases, as evidenced by decreased total superoxide dismutase activities and increased malondialdehyde content. At the transcriptional and metabolic level, PS-NPs primarily induced lipid metabolism disorders, DNA damage, biofilm disruption, and mitochondrial dysfunction. In the gene-metabolite correlation interaction network, numerous CcO (cytochrome c oxidase) family genes and lipid metabolites were identified as key regulatory genes and metabolites in detoxification processes. Among them, the red drum possesses one additional CcO6B in comparison to human and zebrafish, which potentially contributes to its enhanced capacity for maintaining a stable and positive regulatory function in detoxification. This study revealed that nanoplastics cause severe biotoxicity to red drum, which may be detrimental to the survival of wild populations and affect the economics of farmed populations.
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Perciformes , Contaminantes Químicos del Agua , Animales , Humanos , Antioxidantes/metabolismo , Microplásticos/metabolismo , Pez Cebra/genética , Pez Cebra/metabolismo , Perciformes/genética , Perciformes/metabolismo , Estrés Oxidativo , Poliestirenos/toxicidad , Contaminantes Químicos del Agua/toxicidad , Contaminantes Químicos del Agua/metabolismoRESUMEN
The purpose of this study was to investigate the anti-fatigue effect of natural Lycium barbarum polysaccharide (LBP) during exercise, develop a functional anti-fatigue effervescent tablet by applying LBP to practical products, and help patients who have difficulty swallowing conventional tablets or capsules. LBP was extracted with water, and DEAE-52 cellulose was used for purification. The chemical structure and monosaccharide composition of LBP by Fourier transform infrared spectroscopy (FI-IR) and ion chromatography (IC). Lycium barbarum polysaccharide effervescent tablets (LBPT) were prepared by mixing LBP and an excipient. Animal experiments showed that LBP and LBPT significantly increased the exhaustive swimming time in rats. LBP and LBPT improved biochemical markers in rat serum, such as lactic acid and creatine kinase, enhanced the antioxidant capacity of rat muscle, and reversed the decrease in serum glucose, ATP and glycogen content caused by exercise. Transmission electron microscopy showed that LBP and LBPT increased the density of mitochondria in rat liver. In addition, molecular experiments showed that LBP and LBPT could improve oxidative stress caused by exercise by regulating the Nrf2/HO-1 signaling pathway and regulating energy metabolism via the AMPK/PGC-1α signaling pathway.
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Medicamentos Herbarios Chinos , Lycium , Proteínas Quinasas Activadas por AMP/metabolismo , Adenosina Trifosfato/metabolismo , Animales , Antioxidantes/farmacología , Celulosa/metabolismo , Creatina Quinasa/metabolismo , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Metabolismo Energético , Excipientes/farmacología , Glucosa/metabolismo , Glucógeno/metabolismo , Ácido Láctico/farmacología , Lycium/metabolismo , Monosacáridos/farmacología , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo , Ratas , Comprimidos/farmacología , Agua/farmacologíaRESUMEN
Objective To explore the mechanism of puerarin inhibiting the proliferation,invasion,and migration of non-small cell lung cancer cells. Methods A549 cells were cultured and treated with different concentrations of puerarin.The inhibition rate (IR) on cell proliferation was detected by CCK-8,and qRT-PCR was performed to detect the mRNA levels of miR-490 and denticleless E3 ubiquitin protein ligase(DTL).Double luciferase reporter assay was employed to identify the targets of miR-490 and DTL based on the establishment of NC mimic group,miR-490 mimic group,NC inhibitor group,and miR-490 inhibitor group.The cells treated by 20 µmol/L puerarin were classified into six groups:DMSO,puerarin,puerarin+NC inhibitor,puerarin+miR-490 inhibitor,puerarin+miR-490 inhibitor+Si-NC,and puerarin+miR-490 inhibitor+Si-DTL.Transwell was used to detect cell migration and invasion.Western blotting was performed to detect the protein levels of epithelial-mesenchymal transition-related markers E-cadherin,N-cadherin,and Vimentin. Results With the increase in puerarin concentration,the IR gradually elevated (F=105.375,P<0.001),miR-490 expression gradually increased (F=32.919,P<0.001),and DTL expression gradually decreased (F=116.120,P<0.001).Compared with NC mimic group,miR-490 mimic group had decreased luciferase activity (t=7.762,P=0.016),raised miR-490 mRNA level (t=13.319,P<0.001),and declined DTL mRNA level (t=7.415,P=0.002).Compared with those in NC inhibitor group,miR-490 demonstrated decreased mRNA level (t=9.523,P=0.001) and DTL presented increased mRNA level (t=11.305,P<0.001) in miR-490 inhibitor group.Western blotting showed that the protein level of DTL was higher in NC mimic group (t=7.953,P=0.001) than in miR-490 mimic group and higher in miR-490 inhibitor group than in NC inhibitor group (t=10.552,P<0.001).Compared with DMSO group,puerarin group showed up-regulated mRNA level of miR-490 (t=10.255,P=0.001) while down-regulated mRNA level of DTL (t=6.682,P=0.003).Compared with those in puerarin+NC inhibitor group,the mRNA level of miR-490 declined (t=10.995,P<0.001) while that of DTL raised (t=12.478,P<0.001) in puerarin+miR-490 inhibitor group.The mRNA level of miR-490 had no significant difference between puerarin+miR-490 inhibitor+Si-NC group and puerarin+miR-490 inhibitor+Si-DTL group (t=1.081,P=0.341),and that of DTL was lower in the latter group (t=14.321,P<0.001).The protein level of DTL was higher in puerarin+miR-490 inhibitor group than in puerarin+NC inhibitor group (t=11.423,P<0.001),and lower in puerarin+miR-490 inhibitor+Si-DTL group than in puerarin+miR-490 inhibitor+Si-NC group (t=12.080,P<0.001).Compared with DMSO group,puerarin group showed inhibited cell proliferation (F=129.27,P<0.001).The activity of cell proliferation was higher in puerarin+miR-490 inhibitor group than in puerarin+NC inhibitor group (F=75.12,P<0.001),and higher in puerarin+miR-490 inhibitor+Si-NC group than in puerarin+miR-490 inhibitor+Si-DTL group (F=52.59,P<0.001).Compared with DMSO group,puerarin group had suppressed cell migration (t=8.963,P=0.001).The cell migration ability was higher in puerarin+miR-490 inhibitor group than in puerarin+NC inhibitor group (t=12.117,P<0.001) and higher in puerarin+miR-490 inhibitor+Si-NC group than in puerarin+miR-490 inhibitor+Si-DTL group (t=12.934,P<0.001).Puerarin group showed weakened cell invasion ability compared with DMSO group (t=4.710,P=0.009).The cell invasion ability was higher in puerarin+miR-490 inhibitor group than in puerarin+NC inhibitor group (t=13.264,P<0.001) and lower in puerarin+miR-490 inhibitor+Si-DTL group than in puerarin+miR-490 inhibitor+Si-NC group (t=13.476,P<0.001).Compared with DMSO group,puerarin group showed up-regulated protein level of E-cadherin (t=7.137,P=0.002) while down-regulated protein levels of N-cadherin (t=8.828,P=0.001) and vimentin (t=6.594,P=0.003).Compared with those in puerarin+NC inhibitor group,the protein level of E-cadherin (t=12.376,P<0.001) decreased while those of N-cadherin (t=13.436,P<0.001) and vimentin (t=11.467,P<0.001) increased in puerarin+miR-490 inhibitor group.Compared with puerarin+miR-490 inhibitor+Si-NC group,puerarin+miR-490 inhibitor+Si-DTL group up-regulated the protein level of E-cadherin (t=13.081,P<0.001) while down-regulated the protein levels of N-cadherin (t=10.835,P<0.001) and vimentin (t=11.862,P<0.001). Conclusion Puerarin could inhibit the proliferation,invasion,and migration of non-small cell lung cancer cells by up-regulating miR-490 and down-regulating DTL.
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Carcinoma de Pulmón de Células no Pequeñas , Isoflavonas , Neoplasias Pulmonares , MicroARNs , Ubiquitina-Proteína Ligasas , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Humanos , Isoflavonas/farmacología , MicroARNs/metabolismo , Ubiquitina-Proteína Ligasas/metabolismoRESUMEN
Nanoplastic pollution typically exhibits more biotoxicity to marine organisms than microplastic pollution. Limited research exists on the toxic effects of small-sized nanoplastics on marine fish, especially regarding their post-exposure resilience. In this study, red drum (Sciaenops ocellatus) were exposed to small-sized polystyrene nanoplastics (30 nm, PS-NPs) for 7 days for the exposure experiments, followed by 14 days of recovery experiments. Histologically, hepatic lipid droplets and branchial epithelial liftings were the primary lesions induced by PS-NPs during both exposure and recovery periods. The inhibition of total superoxide dismutase activity and the accumulation of malondialdehyde content throughout the exposure and recovery periods. Transcriptional and metabolic regulation revealed that PS-NPs induced lipid metabolism disorders and DNA damage during the initial 1-2 days of exposure periods, followed by immune responses and neurotoxicity in the later stages (4-7 days). During the early recovery stages (2-7 days), lipid metabolism and cell cycle were activated, while in the later recovery stage (14 days), the emphasis shifted to lipid metabolism and energy metabolism. Persistent histological lesions, changes in antioxidant capacity, and fluctuations in gene and metabolite expression were observed even after 14 days of recovery periods, highlighting the severe biotoxicity of small-sized PS-NPs to marine fish. In summary, small-sized PS-NPs have severe biotoxicity, causing tissue lesions, oxidative damage, lipid metabolism disorders, DNA damage, immune responses, and neurotoxicity in red drum. This study offers valuable insights into the toxic effects and resilience of small-sized nanoplastics on marine fish.
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Perciformes , Contaminantes Químicos del Agua , Animales , Contaminantes Químicos del Agua/toxicidad , Perciformes/fisiología , Microplásticos/toxicidad , Daño del ADN , Nanopartículas/toxicidad , Metabolismo de los Lípidos/efectos de los fármacosRESUMEN
There is limited and sometimes contradictory information about the genotoxicity of the polycyclic aromatic hydrocarbon benzo[ghi]perylene (B[ghi]P). Using recently developed metabolic toxicity screening arrays and a biocolloid reactor-LC-MS/MS approach, both featuring films of DNA and human metabolic enzymes, we demonstrated the relatively low reactivity of metabolically activated B[ghi]P toward DNA. Electro-optical toxicity screening arrays showed that B[ghi]P metabolites damage DNA at a 3-fold lower rate than benzo[a]pyrene (B[a]P), whose metabolites have a strong and well-understood propensity for DNA damage. Metabolic studies using magnetic bead biocolloid reactors coated with microsomal enzymes in 96-well plates showed that cyt P450s 1A1 and 1B1 provide high activity for B[ghi]P and B[a]P conversion. Consistent with published results, the major metabolism of B[ghi]P involved oxidations at 3,4 and 11,12 positions, leading to the formation of B[ghi]P 3,4-oxide and B[ghi]P 3,4,11,12-bisoxide. B[ghi]P 3,4-oxide was synthesized and reacted with deoxyadenosine at N6 and N7 positions and with deoxyguanosine at the N2 position. B[ghi]P 3,4-oxide is hydrolytically unstable and transforms into the 3,4-diol or converts to 3- or 4-hydroxy B[ghi]P. LC-MS/MS of reaction products from the magnetic biocolloid reactor particles coated with DNA and human enzymes revealed for the first time that a major DNA adduct results from the reaction between B[ghi]P 3,4,11,12-bisoxide and deoxyguanosine. Results also demonstrated 5-fold lower formation rates of the major DNA adduct for B[ghi]P metabolites compared to B[a]P. Overall, results from both the electro-optical array and biocolloid reactor-LC-MS/MS consistently suggest a lower human genotoxicity profile of B[ghi]P than B[a]P.
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Benzo(a)pireno/química , Cromatografía Líquida de Alta Presión , ADN/análisis , Espectrometría de Masas en Tándem , Hidrocarburo de Aril Hidroxilasas/metabolismo , Benzo(a)pireno/metabolismo , Benzo(a)pireno/toxicidad , Cromatografía Líquida de Alta Presión/instrumentación , Citocromo P-450 CYP1A1/metabolismo , Citocromo P-450 CYP1B1 , ADN/metabolismo , Aductos de ADN/análisis , Daño del ADN/efectos de los fármacos , Humanos , Magnetismo , Análisis por Micromatrices , Polietilenos/química , Compuestos de Amonio Cuaternario/química , Espectrometría de Masas en Tándem/instrumentaciónRESUMEN
A novel donor (D)-acceptor (A) structured conjugated polymer (PDPP-TP), which contains two alternating D-A pairs, namely thiophene (T)-diketopyrrolopyrrole (DPP) and thiophenen (T)-thieno[3,4-b]pyrazine (TP) along the main chain of the polymer, was synthesized by direct arylation polycondensation (DArP) for a highly efficient photothermal antibacterial treatment. The hydrophilic PDPP-TP-based nanoparticles (PTNPs) with a hydration diameter of about 120 nm were obtained by self-assembly using DSPE-mPEG2000 as the polymer matrix. PTNPs show strong near-infrared (NIR) absorbance with a λmax at 910 nm (ε = 2.25 × 104 L mol-1 cm-1) and NIR light-triggered photoactivity with a high photothermal conversion efficiency (PTCE) of 52.8% under 880 nm laser irradiation. Keeping the merits of excellent biocompatibility and photostability, PTNPs exhibited remarkable bacterial inhibition efficiency of almost 100% against Gram-negative E. coli and Gram-positive S. aureus with the help of an 880 nm laser (0.7 W cm-2, 6 min), demonstrating its great potential as photothermal materials with a broad spectrum of activity for the effective treatment of microbial infections.
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Antiinfecciosos , Nanopartículas , Terapia Fototérmica , Fototerapia , Polímeros/farmacología , Escherichia coli , Staphylococcus aureusRESUMEN
A new molecularly imprinted polymers (MIPs) have been prepared for the high selective extraction of lamotrigine (LTG), a widely used antiepileptic drug, in human serum. The MIPs were polymerized by bulk polymerization using our synthesized compound, 2-(4-vinylphenyl) quinolin-4-carboxylic acid, as functional monomer, which achieved better adsorption specificity than universal MIPs. Then, the molecularly imprinted solid phase extraction (MISPE) based on this material was coupled with high-performance liquid chromatography (HPLC) for the detection of LTG in human serum. The results of method validation showed that the developed method presented a good precision and accuracy, and the linearity was in the range of 1.50-40.00 mg/mL with the limit of quantitation (LOQ) at 0.20 mg/mL. The recovery ranged from 80.8% to 83.8% with RSD ranges from 5.5% to 11.1%. The validated method was successfully used to determine the concentration of LTG in human simulate serum samples.
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Impresión Molecular , Polímeros Impresos Molecularmente , Humanos , Lamotrigina , Anticonvulsivantes , Impresión Molecular/métodos , Polímeros/química , Extracción en Fase Sólida/métodos , Cromatografía Líquida de Alta Presión/métodos , AdsorciónRESUMEN
Carbon dots (CDs) were synthesized with the facile hydrothermal method to produce CDs/polyvinyl alcohol (PVA) active food packaging films. The CDs had a diameter ranging from 2.01 to 5.61 nm and were well-dispersed. The effects of different concentrations of CDs on mechanical strength, water resistance, morphology, optical, and thermal performance of the CDs/PVA films were discussed. The incorporation of CDs in the PVA film improved its mechanical properties, water resistance properties, UV blocking properties, and thermal stability and endowed the composite film with antioxidant and antimicrobial properties. The maximum scavenging rates of 2,2-diphenyl-1-picrylhydrazyl and ABTS free radicals by the 0.50% CDs/PVA film were 72.81 and 97.08%, respectively. The inhibition zone diameters of the 0.50% CDs/PVA solution against Staphylococcus aureus (S. aureus), Bacillus subtilis (B. subtilis), and Escherichia coli (E. coli) were 9.52, 8.21, and 9.05 mm, respectively. Using the 0.50% CDs/PVA film as active packaging, the shelf life of banana, jujube, and fried meatballs was observed to be extended significantly. These results demonstrate the viability of the CDs/PVA composite film as a promising active food packaging material.
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Alcohol Polivinílico , Staphylococcus aureus , Carbono/farmacología , Escherichia coli , Embalaje de Alimentos , Conservación de Alimentos , AguaRESUMEN
Polysuccinimide (abridged as PSI) was synthesized by urea and maleic anhydride. Aminobenzenesulfonic acid (ABSA) was introduced at different mole ratio to PSI to generate polyaspartic acid (abridged as PASP)/ABSA graft copolymer. The scale inhibition behavior of resultant PASP/ABSA copolymer was evaluated by using static scale inhibition method. The transmittance of the supernatant of the copolymer solution was measured to evaluate its dispersion ability for ferric oxide. The corrosion inhibition performance of the copolymer for iron plates immersed in the refined testing water (including 0.555 g of CaCl2 2H2O, 0.493 g of MgSO4 7H2O, 50 mg PASP/ABSA graft copolymer and 0.168 g of NaCl) was tested. It was found that PASP/ABSA copolymer was able to efficiently inhibit CaCO3 and Ca3(PO4)2 scales and had good corrosion inhibition ability as well, and it also had good dispersion ability for Fe2O3. Besides, the inhibition efficiency of PASP/ABSA against CaCO3 and Ca3(PO4)2 scales and its dispersion capacity for Fe2O3 was highly dependent on dosage. The reason may lie in that PASP/ABSA copolymer simultaneously possesses carboxylic ion and sulfonic group which can chelate Ca2+ to form stabilized and dissoluble chelates, resulting in increase of solubility of calcium salts in water. Also it may lie in that the introduction of acidic hydrophilic sulfonic group with a strong electrolytic capacity into PASP molecule simultaneously enhances the dispersion of the inhibitor molecules and hinders the formation of Ca3(PO4)2 scale.
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Péptidos/química , Polímeros/química , Ácidos Sulfanílicos/química , Compuestos Férricos/química , Microscopía Electrónica de Rastreo , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
The aim of this investigation was to develop an etomidate intravenous lipid emulsion (ETM-ILE) and evaluate its properties in vitro and in vivo. Etomidate (ETM) is a hydrophobic drug, and organic solvents must be added to an etomidate injectable solution (ETM-SOL) to aid dissolution, that causes various adverse reactions on injection. Lipid emulsions are a novel drug formulation that can improve drug loading and reduce adverse reactions. ETM-ILE was prepared using high-pressure homogenization. Univariate experiments were performed to select key conditions and variables. The proportion of oil, egg lecithin, and poloxamer 188 (F68) served as variables for the optimization of the ETM-ILE formulation by central composite design response surface methodology. The optimized formulation had the following characteristics: particle size, 168.0 ± 0.3 nm; polydispersity index, 0.108 ± 0.028; zeta potential, -36.4 ± 0.2 mV; drug loading, 2.00 ± 0.01 mg/mL; encapsulation efficiency, 97.65% ± 0.16%; osmotic pressure, 292 ± 2 mOsmol/kg and pH value, 7.63 ± 0.07. Transmission electron microscopy images showed that the particles were spherical or spheroidal, with a diameter of approximately 200 nm. The stability study suggested that ETM-ILE could store at 4 ± 2 °C or 25 ± 2 °C for 12 months. Safety tests showed that ETM-ILE did not cause hemolysis or serious vascular irritation. The results of the pharmacokinetic study found that ETM-ILE was bioequivalent to ETM-SOL. However, a higher concentration of ETM was attained in the liver, spleen, and lungs after administration of ETM-ILE than after administration of ETM-SOL. This study found that ETM-ILE had great potential for clinical applications.
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Anestésicos Intravenosos/administración & dosificación , Anestésicos Intravenosos/farmacocinética , Etomidato/administración & dosificación , Etomidato/farmacocinética , Emulsiones Grasas Intravenosas/química , Anestésicos Intravenosos/farmacología , Animales , Química Farmacéutica , Estabilidad de Medicamentos , Etomidato/farmacología , Concentración de Iones de Hidrógeno , Lecitinas/química , Masculino , Tamaño de la Partícula , Poloxámero/química , Conejos , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Aceite de Soja/química , Propiedades de SuperficieRESUMEN
In pure water system, the specific and rapid detection of cysteine (Cys) is very important and challenging. Herein, a new optical probe was developed for the purpose based on the complex of cupric ion (Cu2+) with a water-soluble conjugated polymer, poly[3-(3-N,N-diacetateaminopropoxy)-4-methyl thiophene disodium salts] (PTCO2). The fluorescence of PTCO2 in 100% aqueous solution can almost completely extinguished by Cu2+ ions due to its intrinsic paramagnetic properties. Among various amino acids, only Cys causes immediately the efficient recovery of the Cu2+-quenched fluorescence of PTCO2 with ~31-folds fluorescence enhancement because of the stronger affinity of Cys to Cu2+ leading to the formation of Cu2+-Cys complex through Cu-S bond and separation of Cu2+ from weak-fluorescent PTCO2-Cu(II) ensemble and thereby restoring the free PTCO2 fluorescence. In tris-HCl buffer solution (2â¯mM, pH 7.4), the intensity of the restored fluorescence is linear with the concentration of Cys, ranging from 0 to 120⯵M and the estimated detection limit of Cys is 3.3â¯×â¯10-7 M with the correlation coefficient R =â¯0.9981. In addition, the PTCO2-Cu(II) ensemble probe exhibits low cytotoxicity and good membrane penetration, and its application in living cell imaging of Cys has also been explored.
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Cobre/química , Cisteína/análisis , Colorantes Fluorescentes/química , Imagen Óptica , Polímeros/química , Supervivencia Celular/efectos de los fármacos , Cobre/farmacología , Relación Dosis-Respuesta a Droga , Colorantes Fluorescentes/farmacología , Células HeLa , Humanos , Concentración de Iones de Hidrógeno , Iones/química , Estructura Molecular , Teoría Cuántica , Solubilidad , Relación Estructura-Actividad , Agua/químicaRESUMEN
Detection of the adenosine 5'-triphosphatase (ATPase) activity in lysosome of living cells is of great importance for clinical diagnosis of many related diseases, including cancer. In this work, a new water-soluble polythiophene derivative named ZnPT bearing both quaternary ammonium salt groups and dipicolylamine-Zn2+ (DPA-Zn2+) complexes in its side chain, was designed and synthesized for this propose. The probe mainly localized to lysosome with good biocompatibility and membrane penetration. The real-time, continuous, direct, and label-free assays were achieved through a fluorescence "turn-on" mode by taking advantages of the reaction specificity of ATPase with ATP and the high binding selectivity of ZnPT toward ATP substrate over its hydrolysis product (ADP). This well designed strategy should provide a facile and effective way for investigating ATPase-relevant biological processes.
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Adenosina Trifosfatasas/análisis , Complejos de Coordinación/química , Lisosomas/enzimología , Sondas Moleculares/química , Polímeros/química , Espectrometría de Fluorescencia/métodos , Tiofenos/química , Adenosina Difosfato/metabolismo , Adenosina Trifosfatasas/metabolismo , Adenosina Trifosfato/metabolismo , Animales , Unión Competitiva , Transporte Biológico , Línea Celular , Complejos de Coordinación/síntesis química , Fibroblastos/citología , Fibroblastos/enzimología , Hidrólisis , Cinética , Lisosomas/metabolismo , Lisosomas/ultraestructura , Ratones , Sondas Moleculares/síntesis química , Permeabilidad , Polímeros/síntesis química , Solubilidad , Tiofenos/síntesis química , Agua/química , Zinc/químicaRESUMEN
A new identification of Gymnothorax minor (Temminck & Schlegel, 1846) is documented based on morphological characteristics and DNA barcoding. Sixty-one individuals of G. minor were collected from the East China Sea and the South China Sea. This species was previously reported as Gymnothorax reticularis Bloch, 1795 in China because of the similarity in external shape and color. Gymnothorax minor can be easily distinguished from G. reticularis by its color pattern of 18-20 irregular dark brown vertical bars and the body having scattered small brown spots. Additionally, the teeth are uniserial on both jaws, and the vertebrae number 137-139. By combining congener sequences of the cytochrome oxidase I (COI) gene from GenBank, two groups were detected among all the COI sequences of the currently named G. minor, which further indicated that two valid species were present based on genetic distance. A divergence also occurred on the number of vertebrae between the northern and southern populations. The phylogenetic and morphological analysis strongly supports that the northern and southern populations of G. minor are two different species. Furthermore, the distribution area of the northern G. minor has expanded southward to 5°15'N in the South China Sea. More specimens of G. minor and G. reticularis are crucial in order to define their geographical distribution boundaries and provide the correct DNA barcoding.
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The discovery of biocompatible or bioactive nanoparticles for medicinal applications is an expensive and time-consuming process that may be significantly facilitated by incorporating more rational approaches combining both experimental and computational methods. However, it is currently hindered by two limitations: (1) the lack of high-quality comprehensive data for computational modeling and (2) the lack of an effective modeling method for the complex nanomaterial structures. In this study, we tackled both issues by first synthesizing a large library of nanoparticles and obtained comprehensive data on their characterizations and bioactivities. Meanwhile, we virtually simulated each individual nanoparticle in this library by calculating their nanostructural characteristics and built models that correlate their nanostructure diversity to the corresponding biological activities. The resulting models were then used to predict and design nanoparticles with desired bioactivities. The experimental testing results of the designed nanoparticles were consistent with the model predictions. These findings demonstrate that rational design approaches combining high-quality nanoparticle libraries, big experimental data sets, and intelligent computational models can significantly reduce the efforts and costs of nanomaterial discovery.
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Materiales Biocompatibles/química , Oro/química , Modelos Químicos , Nanoestructuras/química , Línea Celular Tumoral , Células HEK293 , Hemo-Oxigenasa 1/química , Humanos , Relación Estructura-Actividad , Propiedades de SuperficieRESUMEN
A biomineralized hydrogel system containing hyaluronic acid (HA) and poloxamer composed of a poly(ethylene oxide)/poly(propylene oxide)/poly(ethylene oxide) (PEO-PPO-PEO) block copolymer was developed as a biomimetic thermo-responsive injectable hydrogel system for bone regeneration. Using HA and poloxamer macromers with polymerizable residues, organic/inorganic HA/poloxamer hydrogels with various compositions were prepared and subjected to a biomineralization process to mimic the bone extracellular matrix. An increase in HA content within the hydrogels enhanced intermolecular chelation with calcium ions, leading to an increase in nucleation and growth of calcium phosphate in the hydrogels. After the biomineralization procedure, a crystalline formation was observed within and on the surface of the hydrogel. All of the HA/poloxamer hydrogel samples exhibited relatively high water content of greater than 90% at 25 °C, and the water content was influenced by the HA/poloxamer composition, biomineralization, and temperature. In particular, the HA/poloxamer hydrogel was injectable through a syringe without demonstrating appreciable macroscopic fracture at room temperature, whereas it was more opaque and adopted a more rigid structure as the temperature increased because of the increasing hydrophobicity of poloxamer. The enzymatic degradation behavior of the hydrogels depended on the concentration of hyaluronidase, HA/poloxamer composition, and biomineralization. The release kinetics of model drugs from HA/poloxamer hydrogels was primarily dependent on the drug loading content, water content, biomineralization of the hydrogels, and ionic properties of the drug. These results indicate that biomineralized HA/poloxamer hydrogel is a promising candidate material for a biomimetic hydrogel system that promotes bone tissue repair and regeneration via local delivery of drugs.
Asunto(s)
Sustitutos de Huesos/química , Portadores de Fármacos/química , Ácido Hialurónico/química , Hidrogeles/química , Poloxámero/química , Polietilenglicoles/química , Glicoles de Propileno/química , Biomimética , Sustitutos de Huesos/administración & dosificación , Sustitutos de Huesos/metabolismo , Portadores de Fármacos/administración & dosificación , Portadores de Fármacos/metabolismo , Liberación de Fármacos , Humanos , Ácido Hialurónico/administración & dosificación , Ácido Hialurónico/metabolismo , Hialuronoglucosaminidasa/metabolismo , Hidrogeles/administración & dosificación , Hidrogeles/metabolismo , Inyecciones , Modelos Moleculares , Poloxámero/administración & dosificación , Poloxámero/metabolismo , Polietilenglicoles/administración & dosificación , Polietilenglicoles/metabolismo , Glicoles de Propileno/administración & dosificación , Glicoles de Propileno/metabolismo , TemperaturaRESUMEN
The leucine zipper, EF hand-containing transmembrane protein 1 (Letm1) gene encodes a mitochondrial inner membrane protein, whose depletion severely perturbs mitochondrial Ca(2+) and K(+) homeostasis. Here we expressed, purified, and reconstituted human Letm1 protein in liposomes. Using Ca(2+) fluorophore and (45)Ca(2+)-based assays, we demonstrate directly that Letm1 is a Ca(2+) transporter, with apparent affinities of cations in the sequence of Ca(2+) ≈ Mn(2+) > Gd(3+) ≈ La(3+) > Sr(2+) >> Ba(2+), Mg(2+), K(+), Na(+). Kinetic analysis yields a Letm1 turnover rate of 2 Ca(2+)/s and a Km of â¼25 µM. Further experiments show that Letm1 mediates electroneutral 1 Ca(2+)/2 H(+) antiport. Letm1 is insensitive to ruthenium red, an inhibitor of the mitochondrial calcium uniporter, and CGP-37157, an inhibitor of the mitochondrial Na(+)/Ca(2+) exchanger. Functional properties of Letm1 described here are remarkably similar to those of the H(+)-dependent Ca(2+) transport mechanism identified in intact mitochondria.
Asunto(s)
Antiportadores/metabolismo , Proteínas de Unión al Calcio/metabolismo , Proteínas de Transporte de Catión/metabolismo , Proteínas de la Membrana/metabolismo , Proteínas Mitocondriales/metabolismo , Calcio/metabolismo , Cationes Bivalentes/metabolismo , Clonazepam/análogos & derivados , Clonazepam/farmacología , Humanos , Transporte Iónico , Liposomas/metabolismo , Potasio/metabolismo , Rojo de Rutenio/farmacología , Sodio/metabolismo , Tiazepinas/farmacologíaRESUMEN
Algal bloom could drastically influence the nutrient cycling in lakes. To understand how the internal nutrient release responds to algal bloom decay, water and sediment columns were sampled at 22 sites from four distinct regions of China's eutrophic Lake Taihu and incubated in the laboratory to examine the influence of massive algal bloom decay on nutrient release from sediment. The column experiment involved three treatments: (1) water and sediment (WS); (2) water and algal bloom (WA); and (3) water, sediment, and algal bloom (WSA). Concentrations of dissolved oxygen (DO), total nitrogen (TN), total phosphorus (TP), ammonium (NH (4) (+) -N), and orthophosphate (PO (4) (3-) -P) were recorded during incubation. The decay of algal material caused a more rapid decrease in DO than in the algae-free controls and led to significant increases in NH (4) (+) -N and PO (4) (3-) -P in the water. The presence of algae during the incubation had a regionally variable effect on sediment nutrient profiles. In the absence of decaying algae (treatment WS), sediment nutrient concentrations decreased during the incubation. In the presence of blooms (WSA), sediments from the river mouth released P to the overlying water, while sediments from other regions absorbed surplus P from the water. This experiment showed that large-scale algal decay will dramatically affect nutrient cycling at the sediment-water interface and would potentially transfer the function of sediment as "container" or "supplier" in Taihu, although oxygen exchange with atmosphere in lake water was stronger than in columns. The magnitude of the effect depends on the physical-chemical character of the sediments.