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1.
J Nanobiotechnology ; 22(1): 94, 2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38449005

RESUMEN

BACKGROUND: Impaired osteo-/angiogenesis, excessive inflammation, and imbalance of the osteoimmune homeostasis are involved in the pathogenesis of the alveolar bone defect caused by periodontitis. Unfortunately, there is still a lack of ideal therapeutic strategies for periodontitis that can regenerate the alveolar bone while remodeling the osteoimmune microenvironment. Quercetin, as a monomeric flavonoid, has multiple pharmacological activities, such as pro-regenerative, anti-inflammatory, and immunomodulatory effects. Despite its vast spectrum of pharmacological activities, quercetin's clinical application is limited due to its poor water solubility and low bioavailability. RESULTS: In this study, we fabricated a quercetin-loaded mesoporous bioactive glass (Quercetin/MBG) nano-delivery system with the function of continuously releasing quercetin, which could better promote the bone regeneration and regulate the immune microenvironment in the alveolar bone defect with periodontitis compared to pure MBG treatment. In particular, this nano-delivery system effectively decreased injection frequency of quercetin while yielding favorable therapeutic results. In view of the above excellent therapeutic effects achieved by the sustained release of quercetin, we further investigated its therapeutic mechanisms. Our findings indicated that under the periodontitis microenvironment, the intervention of quercetin could restore the osteo-/angiogenic capacity of periodontal ligament stem cells (PDLSCs), induce immune regulation of macrophages and exert an osteoimmunomodulatory effect. Furthermore, we also found that the above osteoimmunomodulatory effects of quercetin via macrophages could be partially blocked by the overexpression of a key microRNA--miR-21a-5p, which worked through inhibiting the expression of PDCD4 and activating the NF-κB signaling pathway. CONCLUSION: In summary, our study shows that quercetin-loaded mesoporous nano-delivery system has the potential to be a therapeutic approach for reconstructing alveolar bone defects in periodontitis. Furthermore, it also offers a new perspective for treating alveolar bone defects in periodontitis by inhibiting the expression of miR-21a-5p in macrophages and thereby creating a favorable osteoimmune microenvironment.


Asunto(s)
FN-kappa B , Periodontitis , Humanos , Quercetina/farmacología , Periodontitis/tratamiento farmacológico , Flavonoides , Inflamación , Proteínas de Unión al ARN , Proteínas Reguladoras de la Apoptosis
2.
J Nanobiotechnology ; 20(1): 272, 2022 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-35690763

RESUMEN

BACKGROUND: Acute lung injury (ALI), a severe health-threatening disease, has a risk of causing chronic pulmonary fibrosis. Informative and powerful evidence suggests that inflammation and oxidative stress play a central role in the pathogenesis of ALI. Quercetin is well recognized for its excellent antioxidant and anti-inflammatory properties, which showed great potential for ALI treatment. However, the application of quercetin is often hindered by its low solubility and bioavailability. Therefore, to overcome these challenges, an inhalable quercetin-alginate nanogel (QU-Nanogel) was fabricated, and by this special "material-drug" structure, the solubility and bioavailability of quercetin were significantly enhanced, which could further increase the activity of quercetin and provide a promising therapy for ALI. RESULTS: QU-Nanogel is a novel alginate and quercetin based "material-drug" structural inhalable nanogel, in which quercetin was stabilized by hydrogen bonding to obtain a "co-construct" water-soluble nanogel system, showing antioxidant and anti-inflammatory properties. QU-Nanogel has an even distribution in size of less than 100 nm and good biocompatibility, which shows a stronger protective and antioxidant effect in vitro. Tissue distribution results provided evidence that the QU-Nanogel by ultrasonic aerosol inhalation is a feasible approach to targeted pulmonary drug delivery. Moreover, QU-Nanogel was remarkably reversed ALI rats by relieving oxidative stress damage and acting the down-regulation effects of mRNA and protein expression of inflammation cytokines via ultrasonic aerosol inhalation administration. CONCLUSIONS: In the ALI rat model, this novel nanogel showed an excellent therapeutic effect by ultrasonic aerosol inhalation administration by protecting and reducing pulmonary inflammation, thereby preventing subsequent pulmonary fibrosis. This work demonstrates that this inhalable QU-Nanogel may function as a promising drug delivery strategy in treating ALI.


Asunto(s)
Lesión Pulmonar Aguda , Fibrosis Pulmonar , Lesión Pulmonar Aguda/tratamiento farmacológico , Alginatos , Animales , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Antioxidantes/química , Inflamación , Nanogeles , Tamaño de la Partícula , Quercetina/farmacología , Quercetina/uso terapéutico , Ratas
3.
Mikrochim Acta ; 189(6): 239, 2022 05 31.
Artículo en Inglés | MEDLINE | ID: mdl-35639192

RESUMEN

Polyamidamine (PAMAM) dendrimer-functionalized hydrothermal nanosized carbonaceous spheres (HNCSs) were prepared and utilized as latexes for agglomerated anion exchange chromatography (AEC) stationary phase. The high-concentration and scalable production of monodisperse HNCSs (73-98 nm) was accomplished via the polyquaternium-7-assisted hydrothermal carbonization of fructose. The novel PAMAM-based quaternizations of HNCSs were designed by the amidation with PAMAM and epoxy-amine addition reaction with glycidol in aqueous solution. The mild functionalization condition leads to well-kept morphology of HNCSs, which forms one even latex layer on the sulfonated surface of polystyrene-divinylbenzene microbeads for the construction of AEC packing. Under isocratic elution, seven common inorganic anions and five organic acids were baseline separated in 9 min on prepared packing with efficiencies of 54,000-79,800 plates m-1 and asymmetry factor (As) of 1.02-1.12. The obtained separation efficiency, peak symmetry, and analysis time were superior to reported or typical commercial counterparts. The quick separation of polarizable anions in 7 min and carbohydrates in 5 min could also be carried out with symmetrical peaks (As: 1.00-1.18) and high efficiencies (49,700-62,100 N/m). Favorable stability and reproducibility were proved by continuous flushing and injection. The constructed packings were further applied to the determination of thiosulfate and sulfate in water reducer, galacturonic acid in Angelica polysaccharide hydrolysate, and fluoride samples in 4 min.


Asunto(s)
Dendrímeros , Aniones/química , Cromatografía por Intercambio Iónico/métodos , Látex , Poliestirenos/química , Reproducibilidad de los Resultados
4.
BMC Oral Health ; 22(1): 439, 2022 10 08.
Artículo en Inglés | MEDLINE | ID: mdl-36209217

RESUMEN

BACKGROUND: Periodontal accelerated osteogenic orthodontics (PAOO) is a widely-used clinical procedure that combines selective alveolar corticotomy, particulate bone grafting, and the application of orthodontic forces. Different modifications of PAOO such as collagen-membrane coverage can better benefit patients from preventing displacement of grafts. Due to its stability, collagen-membrane coverage gradually gained popularity and became a widely-used procedure in traditional PAOO technique. OBJECTIVES: To quantitatively investigate the radiographic changes of alveolar bone, periodontal soft tissue changes of the mandibular anterior teeth and postoperative complications in periosteum-covered techniques compared with traditional surgical technique in PAOO. METHODS: Orthodontic camouflage for dental Class II or decompensation for skeletal Class III malocclusions were included; Patients with bone defects on the buccal aspects of the anterior mandible regions confirmed by clinical and radiographic examination were randomly divided into the periosteum coverage group or traditional technique group for PAOO. Cone-beam computerized tomography (CBCT) scans were obtained before treatment (T0) and 1 week (T1) and 12 months (T2) after operation. The primary outcome variable was the vertical alveolar bone level (VBL), the secondary evaluation parameters included labial horizontal bone thickness at the midpoint of the middle third (MHBT) or apical third (AHBT) to the limit of the labial cortical surface during a 12-month follow-up. Postoperative sequelae were evaluated after 2 days and 7 days in both the groups. Periodontal parameters were analyzed at T0 and T2. RESULTS: Thirty-six adult subjects were eligible and recruited in the present study. Although experimental group exhibited more severe infection, no significant differences of the postoperative symptoms or periodontal parameters was found between the 2 groups (P > 0.05). All patients were examined respectively using CBCT at baseline (T0), postoperative 1 week (T1) and 12 months (T2). Both alveolar bone height and width increased from T0 to T1 (P < 0.001) and then reduced from T1 to T2 (P < 0.001) in both groups. However, significant bone augmentation was achieved in each group from T0 to T2 (P < 0.001). Furthermore, the vertical alveolar bone augmentation in the experimental group increased significantly than that in the traditional surgery (P < 0.05). CONCLUSIONS: Compared with traditional PAOO surgery, the periosteum-covered technique provides superior graft stabilization and satisfactory vertical bone augmentation in the labial mandibular anterior area.


Asunto(s)
Maloclusión de Angle Clase III , Ortodoncia , Adulto , Colágeno/uso terapéutico , Tomografía Computarizada de Haz Cónico/métodos , Humanos , Maloclusión de Angle Clase III/cirugía , Periostio/diagnóstico por imagen , Periostio/cirugía
5.
J Fluoresc ; 30(5): 1233-1240, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32757089

RESUMEN

A novel luminescent coordination polymer (CP) based on Zn(II) ions as nodes [Zn(OPY)1.5(Hbtc)]n (1), [H3btc = trimesic acid and OPY = 4,4'-(oxybis(4,1-phenylene))dipyridine] has been prepared via the solvothermal assembly of a tripodal multicarboxylic acid ligand, a bis-pyridyl ligand with V-shape containing two diverse coordination patterns as well as Zn2 + ion. The experiments of photoluminescence also reflect that the coordination polymer 1 has high sensitivity to potassium dichromate, and its quenching efficiency is Ksv of 2.12 × 104 L·mol- 1. Furthermore, its treatment activity on orthodontic root absorption was evaluated in vivo. Firstly, the CCK-8 assay was performed in this research to evaluate the biotoxicity of the synthetic compound. Next, the TNF-α and Cbfα1 released by the periodontal ligament fibroblast was determined via the ELISA test kit. In addition to this, the signaling pathway of NF-κB activation after treated with compound was measured by the RT-PCR.


Asunto(s)
Complejos de Coordinación/farmacología , Inflamación/tratamiento farmacológico , Sustancias Luminiscentes/farmacología , Resorción Radicular/tratamiento farmacológico , Raíz del Diente/efectos de los fármacos , Zinc/farmacología , Animales , Línea Celular , Complejos de Coordinación/síntesis química , Complejos de Coordinación/química , Inflamación/metabolismo , Sustancias Luminiscentes/síntesis química , Sustancias Luminiscentes/química , Dicromato de Potasio/análisis , Ratas , Ratas Wistar , Resorción Radicular/metabolismo , Raíz del Diente/metabolismo , Zinc/química
6.
J Sep Sci ; 43(11): 2105-2114, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32135026

RESUMEN

Cell membrane chromatography is a powerful tool for screening active components from complex matrices. New cell membrane carriers need to be developed to increase the coverage of cell membranes on the surface of stationary phases, thereby improving cell membrane chromatographic retention. In this work, we prepared polyvinyl alcohol-poly dimethyl diallyl ammonium chloride modified silica gel as a cell membrane carrier. Osteoblast cell was used as cell membrane source, which was widely used to evaluate the osteogenic activity of drugs. The new cell membrane chromatographic stationary phase was used to screen anti-osteoporosis components in Liuwei Dihuang decoction-containing serum. The chemical structures of the new modified materials were characterized by scanning electronic microscopy, Fourier transform infrared spectroscopy, and elemental analysis characterization. Compared with the common cell membrane column, the cell membrane coverage of this modified material was increased by 30%, and thus provided a stronger retention effect in positive drugs. Nineteen metabolites in rat serum samples were retained on the cell membrane chromatography and identified by ultra-high-performance liquid chromatography/time-of-flight mass spectrometry. Among those, four components (morroniside, catalpol, loganin, and acteoside) were selected for in vitro pharmacodynamics validation. They significantly increased the osteoblast proliferation. The new modified material was successfully applied to screen anti-osteoporosis components from Liuwei Dihuang Decoction-containing serum.


Asunto(s)
Membrana Celular/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Osteoporosis/tratamiento farmacológico , Extractos Vegetales/farmacología , Alcohol Polivinílico/química , Administración Oral , Animales , Membrana Celular/química , Proliferación Celular/efectos de los fármacos , Cromatografía Líquida de Alta Presión , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/análisis , Medicamentos Herbarios Chinos/química , Espectrometría de Masas , Medicina Tradicional China , Osteoblastos/efectos de los fármacos , Extractos Vegetales/administración & dosificación , Extractos Vegetales/sangre , Alcohol Polivinílico/síntesis química , Ratas
7.
Mar Drugs ; 18(12)2020 Nov 26.
Artículo en Inglés | MEDLINE | ID: mdl-33255887

RESUMEN

A super-carbon-chain compound, named gibbosol C, featuring a polyoxygenated C70-linear-carbon-chain backbone encompassing two acyclic polyol chains, was obtained from the South China Sea dinoflagellate Amphidinium gibbosum. Its planar structure was elucidated by extensive NMR investigations, whereas its absolute configurations, featuring the presence of 36 carbon stereocenters and 30 hydroxy groups, were successfully established by comparison of NMR data of the ozonolyzed products with those of gibbosol A, combined with J-based configuration analysis, Kishi's universal NMR database, and the modified Mosher's MTPA ester method. Multi-segment modification was revealed as the smart biosynthetic strategy for the dinoflagellate to create remarkable super-carbon-chain compounds with structural diversity.


Asunto(s)
Dinoflagelados/metabolismo , Polímeros/química , Estructura Molecular , Polímeros/aislamiento & purificación
8.
Angew Chem Int Ed Engl ; 59(7): 2606-2611, 2020 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-31814218

RESUMEN

Discrete nanosheets of silicon-doped AlPO4 molecular sieves (SAPO-34) with a thickness of ≈7 nm have been prepared through morphology-reserved synthesis with a lamellar aluminum phosphate as precursor. Cages of the nanosheets are in situ incorporated with copper oxide clusters. The CuO@SAPO-34 nanosheets exhibit a large external surface area with a high number of (010) channel pores on the surface. Due to the thin morphology, copper oxide clusters occupy the outmost cages with a probability >50 %. The distinctive configuration facilitates a new concept of pore mouth catalysis, i.e., reactant molecules larger than the pores cannot enter the interior of the molecular sieves but can interact with the CuO clusters at "the mouth" of the pore. In heterogeneous catalysis, CuO@SAPO-34 nanosheets have shown top performance in one-pot oxidation of cyclohexane to adipic acid by O2 , a key compound for the manufacture of nylon-66, which is so far produced using non-green nitric acid oxidation.

9.
BMC Infect Dis ; 19(1): 866, 2019 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-31638922

RESUMEN

BACKGROUND: Hand, foot and mouth disease (HFMD) remains a burdensome health issue in mainland China. Enterovirus71 (EV-A71) is the main pathogen of severe HFMD. Continuous hemofiltration improves fluid overload, restores kidney function and alleviates inflammatory reactions. The aim of the present study was to evaluate the effects of continuous veno-venous hemodiafiltration (CVVHDF) on severe HFMD caused by EV-A71(EV-A71-HFMD) in a pediatric intensive care unit (PICU). METHODS: A retrospective observational study was performed in a tertiary university PICU from January 2012 to December 2016. Children with severe EV-A71-HFMD complicated by cardiopulmonary failure were included. The patients were divided into a CVVHDF group and a conventional therapy (control) group (non-CVVHDF). The demographics, characteristics, and outcomes between the groups were collected and analyzed. RESULTS: Twenty-nine patients with severe EV-A71-HFMD were enrolled. The 28-day mortality was 17.6% (3/17) in the CVVHDF group and 33.3% (4/12) in the non-CVVHDF group, with no statistical significance between the two groups (P = 0.403). The median interval between CVVHDF initiation and PICU admission was 6 (4,8.5) hrs, and the median duration of CVVHDF was 48 (36, 64) hrs. The left ventricular ejection fraction (LVEF) and cardiac index (CI) in the CVVHDF group were improved after treatment. The plasma levels of catecholamines and renin-angiotensin-aldosterone system (RAAS) substances in the CVVHDF group were significantly decreased after treatment. The decreased catecholamines and RAAS substances included adrenalin (169.8 [145.5, 244.6] vs. 148.0 [109.0, 208.1] ng/L, P = 0.033), dopamine (152.7 [97.0, 191.1] vs. 96.0 [68.0, 160.9] ng/L, P = 0.026), angiotensin II (185.9 [125.2, 800.0] vs. 106.0 [90.8, 232.5] ng/L, P = 0.047), aldosterone (165.7 [94.0, 353.3] vs. 103.3 [84.3, 144.3] ng/L, P = 0.033), and renin (1.12 [0.74, 3.45] vs. 0.79 [0.52, 1.25] µg/L/h, P = 0.029), CONCLUSIONS: CVVHDF reduced the levels of catecholamines and RAAS substances and improved cardiovascular function. Continuous hemodiafiltration may represent a potential therapy in patients with severe EV-A71-HFMD complicated with cardiopulmonary failure.


Asunto(s)
Enfermedades Cardiovasculares/terapia , Terapia de Reemplazo Renal Continuo , Enterovirus Humano A , Enfermedad de Boca, Mano y Pie/terapia , Enfermedad de Boca, Mano y Pie/virología , Unidades de Cuidado Intensivo Pediátrico , Enfermedad Pulmonar Obstructiva Crónica/terapia , Aldosterona/sangre , Angiotensina II/sangre , Enfermedades Cardiovasculares/complicaciones , Catecolaminas/sangre , Preescolar , China , Femenino , Estudios de Seguimiento , Enfermedad de Boca, Mano y Pie/sangre , Enfermedad de Boca, Mano y Pie/complicaciones , Hemodiafiltración/métodos , Humanos , Lactante , Masculino , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Renina/sangre , Sistema Renina-Angiotensina/fisiología , Estudios Retrospectivos , Volumen Sistólico , Resultado del Tratamiento
10.
Bioconjug Chem ; 27(1): 66-73, 2016 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-26629893

RESUMEN

The B-cell-specific Moloney leukemia virus inset site 1 gene (BMI-1) has attracted considerable attention in recent years because of its key role in breast cancer development and metastasis. The downregulation of BMI-1 expression via small interfering RNA (siRNA) effectively inhibits tumor growth. However, the successful application of this therapy is limited by the unavailability of an appropriate vector for siRNA transfer. Therefore, this study aimed to construct a novel laminarin-based nonviral gene transfer vector to carry a constructed BMI-1-targeting siRNA and to investigate the in vitro and in vivo antitumor effects of this siRNA on breast cancer cells. To enhance the siRNA-carrying capacity, we introduced polyethylenimine (PEI) to laminarin's surface via N,N'-carbonyldiimidazole, which produced the cationic PEI-modified laminarin conjugate nLP. Subsequent in vitro experiments indicated that nLP not only formed a nanoparticle with a diameter of 200 nm through electrostatic interactions with siRNA but also showed high efficiency (95.0%) in the delivery siRNA to MCF-7 cells. The nanoparticle targeting BMI-1 (nLP/siBMI-2) reduced BMI-1 expression in breast MCF-7 cells by 90.9% reduction. An in vivo tumor suppression experiment demonstrated that the nLP/siBMI-2 nanoparticle had relatively low toxicity and good gene-therapeutic efficacy, with a tumor inhibition rate of 46.6%.


Asunto(s)
Neoplasias de la Mama/terapia , Terapia Genética/métodos , Proteína Quinasa 7 Activada por Mitógenos/genética , Nanopartículas/química , ARN Interferente Pequeño/administración & dosificación , Animales , Neoplasias de la Mama/genética , Femenino , Técnicas de Transferencia de Gen , Glucanos/química , Humanos , Células MCF-7 , Ratones Endogámicos BALB C , Terapia Molecular Dirigida , Nanopartículas/administración & dosificación , Nanopartículas/toxicidad , Polietileneimina/química , ARN Interferente Pequeño/química , ARN Interferente Pequeño/farmacocinética , Distribución Tisular , Ensayos Antitumor por Modelo de Xenoinjerto
11.
Plant Cell Physiol ; 56(7): 1429-41, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25907569

RESUMEN

Boea hygrometrica resurrection plants require a period of acclimation by slow soil-drying in order to survive a subsequent period of rapid desiccation. The molecular basis of this observation was investigated by comparing gene expression profiles under different degrees of water deprivation. Transcripts were clustered according to the expression profiles in plants that were air-dried (rapid desiccation), soil-dried (gradual desiccation), rehydrated (acclimated) and air-dried after acclimation. Although phenotypically indistinguishable, it was shown by principal component analysis that the gene expression profiles in rehydrated, acclimated plants resemble those of desiccated plants more closely than those of hydrated acclimated plants. Enrichment analysis based on gene ontology was performed to deconvolute the processes that accompanied desiccation tolerance. Transcripts associated with autophagy and α-tocopherol accumulation were found to be activated in both air-dried, acclimated plants and soil-dried non-acclimated plants. Furthermore, transcripts associated with biosynthesis of ascorbic acid, cell wall catabolism, chaperone-assisted protein folding, respiration and macromolecule catabolism were activated and maintained during soil-drying and rehydration. Based on these findings, we hypothesize that activation of these processes leads to the establishment of an optimal physiological and cellular state that enables tolerance during rapid air-drying. Our study provides a novel insight into the transcriptional regulation of critical priming responses to enable survival following rapid dehydration in B. hygrometrica.


Asunto(s)
Aclimatación/genética , Perfilación de la Expresión Génica/métodos , Regulación de la Expresión Génica de las Plantas , Magnoliopsida/genética , Pared Celular/genética , Pared Celular/metabolismo , Desecación , Ontología de Genes , Lignina/metabolismo , Magnoliopsida/metabolismo , Análisis de Secuencia por Matrices de Oligonucleótidos , Hojas de la Planta/genética , Hojas de la Planta/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Agua/metabolismo , Privación de Agua
12.
BMC Musculoskelet Disord ; 16: 254, 2015 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-26370895

RESUMEN

BACKGROUND: Osteomyelitis is a challenge for orthopaedic surgeons. There is a lack of scientific evidence to guide treatment. The purpose of this study was to report the clinical outcome of unplanned retention of antibiotic-impregnated cement spacer (ACS) in the management of osteomyelitis. METHODS: Eight patients (7 with tibial infections and 1 with a calcaneal infection) with osteomyelitis received radical debridement and insertion of an ACS into the bone defect as the definitive management. The mean follow-up period was 2 years (6 months to 4 years). All of these patients had a cement spacer in place. RESULTS: No patient exhibited radiographic evidence of excessive bone loss. The patients reported no or occasional mild pain and exhibited complete weight-bearing abilities, with the exception of one patient who required a crutch because of a spinal cord injury. Signs of recurrence of the osteomyelitis were not noted in any of the patients, and no fractures occurred at last follow-up. CONCLUSION: Our study suggests that a proportion of patients with unplanned retention of ACS appear to function well without necessarily requiring further surgical intervention.


Asunto(s)
Antibacterianos/administración & dosificación , Cementos para Huesos/uso terapéutico , Osteomielitis/diagnóstico , Osteomielitis/tratamiento farmacológico , Tibia/microbiología , Adulto , Anciano , Calcáneo/efectos de los fármacos , Calcáneo/cirugía , Manejo de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Osteomielitis/cirugía , Tibia/efectos de los fármacos , Tibia/cirugía
13.
Mol Pharm ; 11(8): 2612-22, 2014 Aug 04.
Artículo en Inglés | MEDLINE | ID: mdl-24521262

RESUMEN

Synthetic lethal interaction provides a conceptual framework for the development of wiser cancer therapeutics. In this study, we exploited a therapeutic strategy based on the interaction between GATA binding protein 2 (GATA2) downregulation and the KRAS mutation status by delivering small interfering RNA targeting GATA2 (siGATA2) with cationic lipid-assisted polymeric nanoparticles for treatment of non-small-cell lung carcinoma (NSCLC) harboring oncogenic KRAS mutations. Nanoparticles carrying siGATA2 (NPsiGATA2) were effectively taken up by NSCLC cells and resulted in targeted gene suppression. NPsiGATA2 selectively inhibited cell proliferation and induced cell apoptosis in KRAS mutant NSCLC cells. However, this intervention was harmless to normal KRAS wild-type NSCLC cells and HL7702 hepatocytes, confirming the advantage of synthetic lethality-based therapy. Moreover, systemic delivery of NPsiGATA2 significantly inhibited tumor growth in the KRAS mutant A549 NSCLC xenograft murine model, suggesting the therapeutic promise of NPsiGATA2 delivery in KRAS mutant NSCLC therapy.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Factor de Transcripción GATA2/metabolismo , Genes ras , Neoplasias Pulmonares/tratamiento farmacológico , Nanopartículas/química , ARN Interferente Pequeño/metabolismo , Animales , Apoptosis , Transporte Biológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Cationes , Línea Celular Tumoral , Proliferación Celular , Factor de Transcripción GATA2/uso terapéutico , Silenciador del Gen , Hepatocitos/metabolismo , Humanos , Neoplasias Pulmonares/genética , Ratones Desnudos , Microscopía Confocal , Mutación , Nanomedicina/métodos , Polímeros/química , Interferencia de ARN , Ensayos Antitumor por Modelo de Xenoinjerto
14.
Pharmazie ; 69(6): 458-60, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24974582

RESUMEN

The vaginal retention and local irritation of a carrageenan, poloxamer 407 and carbopol-based thermosensitive hydrogel system for vaginal drug delivery was assessed. Results showed that the residence of hydrogel in the mouse vagina following intravaginal administration was prolonged by carrageenan and further prolonged by the addition of a mucoadhesive component (carbopol). The optimal hydrogel formulation was proven to be safe for vaginal use in rabbits.


Asunto(s)
Administración Intravaginal , Hidrogeles/química , Vagina/efectos de los fármacos , Resinas Acrílicas , Adhesividad , Animales , Peso Corporal/efectos de los fármacos , Carragenina , Sistemas de Liberación de Medicamentos , Excipientes , Femenino , Hidrogeles/efectos adversos , Irritantes , Ratones , Ratones Endogámicos ICR , Poloxámero , Conejos , Espectroscopía Infrarroja Corta , Vagina/patología
15.
Environ Pollut ; 343: 123296, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38182010

RESUMEN

Due to their extensive use during and after the COVID-19 pandemic, many disposable face masks are irresponsibly deposited into the water environment, threatening the health of people living nearby. However, the effects of water conditions on the degradation and potential hazards of these masks are generally unclear. This paper entailed the release and cellular toxicity of micro/nano plastics from disposable face masks once discarded in different waters, including soil water, river water, and tap water, with deionized (DI) water as control. At first, polypropylene (PP) was confirmed to be the major component of disposable face masks with Raman and Fourier transform infrared (FTIR) techniques. To monitor the release rate of PP from masks, a silver nanoparticle (AgNP)-based surface-enhanced Raman scattering (SERS) method was established by employing the unique Raman fingerprint of PP at 2882 cm-1. During 30-d incubation in different waters, the release rates of PP, sizes of PP aggregates, length of fibers, and proportions of plastics smaller than 100 nm were in the order of soil water > river water > tap water > DI water. All the obtained PP exhibited significant toxicity in human lung cancer (A549) cells at concentrations of 70 mg/L for 48 h, and the ones obtained in soil water exhibited the most severe damage. Overall, this paper revealed that environmental waters themselves would worsen the adverse effects of disposable face masks, and the key compounds affecting the degradation of masks remain to be clarified. Such information, along with the established methods, could be beneficial in assessing the health risks of disposable face masks in different waters.


Asunto(s)
Nanopartículas del Metal , Agua , Humanos , Polipropilenos/toxicidad , Máscaras , Pandemias , Plata , Suelo , Plásticos/toxicidad
16.
J Mech Behav Biomed Mater ; 151: 106367, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38194787

RESUMEN

Poly (methyl methacrylate) (PMMA) bone cement relies on the loaded antibiotic to realize the antibacterial purpose. But the exothermic behavior during setting often makes temperature-sensitive antibiotics inactivated. It is necessary to develop new material candidates to replace antibiotics. In this study, a new quaternary ammonium methacrylate (QAM) monomer called dimethylaminetriclosan methacrylate (DMATCM) was designed by the quaternization between 2-(Dimethylamino)ethyl methacrylate and triclosan, then employed as the modifier to explore the feasibility of equipping bone cement with antibacterial activity, and to investigate the variations on the physical and biological performances brought by the substitution ratio of DMATCM to MMA. Results showed that DMATCM opened its C=C bonding to participate in the MMA polymerization, and the quaternary ammonium group helped it to perform broad-spectrum antibacterial property against both Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli. With an increased substitution ratio of DMATCM to MMA, the glass transition temperatures, the maximum exothermic temperatures, and the contact angles of bone cements declined, but the residual monomer contents, the fluid uptakes, and the setting times under Vical indentation increased. Long-term soaking made almost no changes to the weight loss and the mechanical properties of DMATCM-modified cements with lower substitution ratios of 0∼20%, and the activation rather enhanced the strengths of uncured AMBC-4 and AMBC-5 samples. Owing to more DMATCM exposed on the cement surface, the inhibition ring diameter produced by modified cement was improved to a maximum of 28.09 mm, and MC3T3-E1 cells performed the cell viabilities all beyond 70% and healthy adhesion after 72 h co-culturing. Taking all measured properties and ISO standards into account, the antibacterial bone cement under the ratio of 10% performed better, besides its good bactericidal effect, the other properties satisfied the requirements for clinical application.


Asunto(s)
Compuestos de Amonio , Polimetil Metacrilato , Polimetil Metacrilato/farmacología , Cementos para Huesos/farmacología , Polimerizacion , Metacrilatos , Ensayo de Materiales , Antibacterianos/farmacología
17.
Int J Biol Macromol ; 265(Pt 2): 130795, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38492696

RESUMEN

The utilization of biomass-based conductive polymer hydrogels in wearable electronics holds great promise for advancing performance and sustainability. An interpenetrating network of polyacrylamide/2-hydroxypropyltrimethyl ammonium chloride chitosan (PAM/HACC) was firstly obtained through thermal-initiation polymerization of AM monomers in the presence of HACC. The positively charged groups on HACC provide strong electrostatic interactions and hydrogen bonding with the PAM polymer chains, leading to improved mechanical strength and stability of the hydrogel network. Subsequently, the PAM/HACC networks served as the skeletons for the in-situ polymerization of polypyrrole (PPy), and then the resulting conductive hydrogel demonstrated stable electromagnetic shielding performance (40 dB), high sensitivity for strain sensing (gauge factor = 2.56). Moreover, the incorporation of quaternary ammonium chitosan into PAM hydrogels enhances their antimicrobial activity, making them more suitable for applications in bacterial contamination or low-temperature environments. This conductive hydrogel, with its versatility and excellent mechanical properties, shows great potential in applications such as electronic skin and flexible/wearable electronics.


Asunto(s)
Resinas Acrílicas , Compuestos de Amonio , Quitosano/análogos & derivados , Compuestos de Amonio Cuaternario , Polímeros , Pirroles , Antibacterianos/farmacología , Conductividad Eléctrica , Hidrogeles
18.
Am J Physiol Gastrointest Liver Physiol ; 305(11): G829-37, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24091600

RESUMEN

Farnesoid X receptor (FXR, Nr1h4) is a ligand-activated transcription factor belonging to the nuclear receptor superfamily. FXR is essential in maintaining bile acid (BA) homeostasis, and FXR(-/-) mice develop cholestasis, inflammation, and spontaneous liver tumors. The signal transducer and activator of transcription 3 (STAT3) is well known to regulate liver growth, and STAT3 is feedback inhibited by its target gene, the suppressor of cytokine signaling 3 (SOCS3). Strong activation of STAT3 was detected in FXR(-/-) mouse livers. However, the mechanism of STAT3 activation with FXR deficiency remains elusive. Wild-type (WT) and FXR(-/-) mice were used to detect STAT3 pathway activation in the liver. In vivo BA feeding or deprivation was used to determine the role of BAs in STAT3 activation, and in vitro molecular approaches were used to determine the direct transcriptional regulation of SOCS3 by FXR. STAT3 was activated in FXR(-/-) but not WT mice. BA feeding increased, but deprivation by cholestyramine reduced, serum inflammatory markers and STAT3 activation. Furthermore, the Socs3 gene was determined as a direct FXR target gene. The elevated BAs and inflammation, along with reduced SOCS3, collectively contribute to the activation of the STAT3 signaling pathway in the liver of FXR(-/-) mice. This study suggests that the constitutive activation of STAT3 may be a mechanism of liver carcinogenesis in FXR(-/-) mice.


Asunto(s)
Hígado/metabolismo , Receptores Citoplasmáticos y Nucleares/metabolismo , Factor de Transcripción STAT3/metabolismo , Animales , Ácidos y Sales Biliares/deficiencia , Ácidos y Sales Biliares/metabolismo , Ácidos y Sales Biliares/farmacología , Resina de Colestiramina/farmacología , Citocinas/sangre , Citocinas/metabolismo , Hígado/efectos de los fármacos , Ratones , Ratones Noqueados , Receptores Citoplasmáticos y Nucleares/genética , Factor de Transcripción STAT3/genética , Proteína 3 Supresora de la Señalización de Citocinas , Proteínas Supresoras de la Señalización de Citocinas/genética , Proteínas Supresoras de la Señalización de Citocinas/metabolismo , Transcripción Genética
19.
Inorg Chem ; 52(10): 5914-23, 2013 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-23634904

RESUMEN

In this Article, self-assembly of AgX (X = NO3(-) and ClO4(-)) salts and four flexible unsymmetrical bis(pyridyl) ligands, namely, N-(pyridin-2-ylmethyl)pyridin-3-amine (L1), N-(pyridin-3-ylmethyl)pyridin-2-amine (L2), N-(pyridin-4-ylmethyl)pyridin-2-amine (L3), and N-(pyridin-4-ylmethyl)pyridin-3-amine (L4), results in the formation of eight helical silver(I) coordination polymers, [Ag(L)(NO3)]n [L = L1 (1), L2 (2), L3 (3), L4 (4)] and [Ag(L)(ClO4)]n [L = L1 (5), L2 (6), L3 (7), L4 (8)], which have been characterized by elemental analysis, IR, TG, PL, and powder and single-crystal X-ray diffraction. The alternating one-dimensional (1-D) left- and right-handed helical chains are included in achiral complexes 1-3 and 5-8. By contrast, the ligand L4 only alternately bridges Ag(I) cation to form the 1-D right-handed helical chain in complex 4. The pitches of these helical chains locate in the range 5.694(5)-17.016(6) Å. Meanwhile, the present four unsymmetrical bis(pyridyl) ligands in the eight complexes present diverse cis-trans and trans-trans conformation and facilitate the construction of helical structures. Moreover, the solid-state luminescent emission intensities of the perchlorate-containing complexes are stronger than those of nitrate-containing complexes at room temperature.


Asunto(s)
Compuestos Organometálicos/síntesis química , Polímeros/química , Piridinas/química , Plata/química , Cristalografía por Rayos X , Ligandos , Modelos Moleculares , Estructura Molecular , Compuestos Organometálicos/química
20.
Luminescence ; 28(6): 948-53, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23281191

RESUMEN

The oxidation reaction between cerium(IV) and Tween 85 in sulfuric acid medium produced weak chemiluminescence (CL). In this paper, it was found that citrate could strongly enhance the CL of cerium(IV)-Tween 85-polyphenol system. Based on studies of ultraviolet-visible spectra and CL spectra, the CL enhancement mechanism had been proposed. It was surmised that the light emission was from an excited oxygen molecular pair O2((1)Δg)O2((1)∑g(-)). The maximum emission wavelength was about 478 nm. The effects of 17 amino acids and 29 organic compounds on cerium(IV)-Tween 85-citrate CL were investigated by a flow injection procedure. This study showed the present system had a wide application for the determination of these compounds.


Asunto(s)
Aminoácidos/análisis , Cerio/química , Luminiscencia , Compuestos Orgánicos/análisis , Polisorbatos/química , Ácido Cítrico/química , Mediciones Luminiscentes , Oxígeno/química , Polifenoles/química , Espectrofotometría Ultravioleta
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