Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 29
Filtrar
Más filtros










Base de datos
Intervalo de año de publicación
1.
Front Pharmacol ; 15: 1374158, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38887554

RESUMEN

Nonalcoholic fatty liver disease (NAFLD) is marked by hepatic steatosis accompanied by an inflammatory response. At present, there are no approved therapeutic agents for NAFLD. Dendrobium Huoshanense polysaccharide (DHP), an active ingredient extracted from the stems of Dendrobium Huoshanense, and exerts a protective effect against liver injury. However, the therapeutic effects and mechanisms of action DHP against NAFLD remain unclear. DHP was extracted, characterized, and administered to mice in which NAFLD had been induced with a high-fat and high-fructose drinking (HFHF) diet. Our results showed that DHP used in this research exhibits the characteristic polysaccharide peak with a molecular weight of 179.935 kDa and is composed primarily of Man and Glc in a molar ratio of 68.97:31.03. DHP treatment greatly ameliorated NAFLD by significantly reducing lipid accumulation and the levels of liver function markers in HFHF-induced NAFLD mice, as evidenced by decreased serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol (TC) and total triglyceride (TG). Furthermore, DHP administration reduced hepatic steatosis, as shown by H&E and Oil red O staining. DHP also inhibited the Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway expression, thereby reducing levels of hepatic proinflammatory cytokines. Besides, untargeted metabolomics further indicated that 49 metabolites were affected by DHP. These metabolites are strongly associated the metabolism of glycine, serine, threonine, nicotinate and nicotinamide, and arachidonic acid. In conclusion, DHP has a therapeutic effect against NAFLD, whose underlying mechanism may involve the modulation of TLR4/NF-κB, reduction of inflammation, and regulation of the metabolism of glycine, serine, threonine, nicotinate and nicotinamide metabolism, and arachidonic acid metabolism.

2.
Front Physiol ; 15: 1354530, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38440345

RESUMEN

The melon fly, Bactrocera cucurbitae (Coquillett) (Tephritidae: Diptera), is an invasive pest that poses a significant threat to agriculture in Africa and other regions. Flies are known to use their olfactory systems to recognise environmental chemical cues. However, the molecular components of the chemosensory system of B. cucurbitae are poorly characterised. To address this knowledge gap, we have used next-generation sequencing to analyse the antenna transcriptomes of sexually immature B. cucurbitae adults. The results have identified 160 potential chemosensory genes, including 35 odourant-binding proteins (OBPs), one chemosensory protein (CSP), three sensory neuron membrane proteins (SNMPs), 70 odourant receptors (ORs), 30 ionotropic receptors (IRs), and 21 gustatory receptors (GRs). Quantitative real-time polymerase chain reaction quantitative polymerase chain reaction was used to validate the results by assessing the expression profiles of 25 ORs and 15 OBPs. Notably, high expression levels for BcucOBP5/9/10/18/21/23/26 were observed in both the female and male antennae. Furthermore, BcucOROrco/6/7/9/13/15/25/27/28/42/62 exhibited biased expression in the male antennae, whereas BcucOR55 showed biased expression in the female antennae. This comprehensive investigation provides valuable insights into insect olfaction at the molecular level and will, thus, help to facilitate the development of enhanced pest management strategies in the future.

3.
Dalton Trans ; 53(9): 4291-4298, 2024 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-38345325

RESUMEN

Studying the effect of morphology on the circularly polarized luminescence (CPL) of chiral molecular materials is important for the development of CPL-active materials for applications. Herein, we report that the morphology of Gd(NO3)3/R-,S-AnempH2 [AnempH2 = (1-anthrylethylamino)methylphosphonic acid] assemblies can be controlled by solvent modulation to form spiral bundles Gd(R-,S-AnempH)3·2H2O (R-,S-1), crystals Gd(R-,S-AnempH)3·2H2O (R-,S-2) and spindle-shaped particles Gd(R-,S-AnempH)3·3H2O·0.5DMF (R-,S-3) with similar chain structures. Interestingly, R-,S-1 are CPL active and show the highest value of dissymmetric factor among the three pairs of enantiomers (|glum| = 2.1 × 10-3), which is 2.8 times larger than that of R-,S-2, while R-,S-3 are CPL inactive with |glum| ≈ 0. This work provides a new route to control the morphology of chiral coordination polymers and improve their CPL performance.

4.
J Am Chem Soc ; 145(44): 23948-23962, 2023 Nov 08.
Artículo en Inglés | MEDLINE | ID: mdl-37886816

RESUMEN

Assembling macroscopic helices with controllable chirality and understanding their formation mechanism are highly desirable but challenging tasks for artificial systems, especially coordination polymers. Here, we utilize solvents as an effective tool to induce the formation of macroscopic helices of chiral coordination polymers (CPs) and manipulate their helical sense. We chose the Ni/R-,S-BrpempH2 system with a one-dimensional tubular structure, where R-,S-BrpempH2 stands for R-,S-(1-(4-bromophenyl)ethylaminomethylphosphonic acid). The morphology of the self-assemblies can be controlled by varying the cosolvent in water, resulting in the formation of twisted ribbons of R-,S-Ni(Brpemp)(H2O)·H2O (R-,S-2T) in pure H2O; needle-like crystals of R-,S-Ni(Brpemp)(H2O)2·1/3CH3CN (R-,S-1C) in 20 vol % CH3CN/H2O; nanofibers of R-,S-Ni(Brpemp)(H2O)·H2O (R-,S-3F) in 20-40 vol % methanol/H2O or ethanol/H2O; and superhelices of R-,S-Ni(Brpemp)(H2O)·H2O (R-,S-4H or 5H) in 40 vol % propanol/H2O. Interestingly, the helicity of the superhelix can be controlled by using a propanol isomer in water. For the Ni/R-BrpempH2 system, a left-handed superhelix of R-4H(M) was obtained in 40 vol % NPA/H2O, while a right-handed superhelix of R-5H(P) was isolated in 40 vol % IPA/H2O. These results were rationalized by theoretical calculations. Adsorption studies revealed the chiral recognition behavior of these compounds. This work may contribute to the development of chiral CPs with a macroscopic helical morphology and interesting functionalities.

5.
Front Microbiol ; 14: 1235620, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37869659

RESUMEN

Seneca Valley virus (SVV), a member of the Picornaviridae family, may cause serious water blister diseases in pregnant sows and acute death in newborn piglets, which have resulted in economic losses in pig production. The 3C protease is a vital enzyme for SVV maturation and is capable of regulating protein cleavage and RNA replication of the virus. Additionally, this protease can impede the host's innate immune response by targeting the interferon pathway's principal factor and enhance virus replication by modulating the host's RNA metabolism while simultaneously triggering programmed cell death. This article reviews recent studies on SVV 3C functions, which include viral replication promotion, cell apoptosis modulation and host immune response evasion, and provides a theoretical basis for research on preventing and controlling SVV infection.

6.
Front Immunol ; 14: 1196031, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37283741

RESUMEN

Swine acute diarrhoea syndrome coronavirus (SADS-CoV), which is a recently discovered enteric coronavirus, is the major aetiological agent that causes severe clinical diarrhoea and intestinal pathological damage in pigs, and it has caused significant economic losses to the swine industry. Nonstructural protein 5, also called 3C-like protease, cleaves viral polypeptides and host immune-related molecules to facilitate viral replication and immune evasion. Here, we demonstrated that SADS-CoV nsp5 significantly inhibits the Sendai virus (SEV)-induced production of IFN-ß and inflammatory cytokines. SADS-CoV nsp5 targets and cleaves mRNA-decapping enzyme 1a (DCP1A) via its protease activity to inhibit the IRF3 and NF-κB signaling pathways in order to decrease IFN-ß and inflammatory cytokine production. We found that the histidine 41 and cystine 144 residues of SADS-CoV nsp5 are critical for its cleavage activity. Additionally, a form of DCP1A with a mutation in the glutamine 343 residue is resistant to nsp5-mediated cleavage and has a stronger ability to inhibit SADS-CoV infection than wild-type DCP1A. In conclusion, our findings reveal that SADS-CoV nsp5 is an important interferon antagonist and enhance the understanding of immune evasion by alpha coronaviruses.


Asunto(s)
Alphacoronavirus , Coronavirus , Interferón Tipo I , Animales , Porcinos , Alphacoronavirus/genética , Alphacoronavirus/metabolismo , Coronavirus/metabolismo , Endopeptidasas , Interferón Tipo I/metabolismo
7.
SAGE Open Med ; 11: 20503121231167964, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37205157

RESUMEN

Ageratina adenophora is an invasive weed with widespread distribution. During the last several decades, many biologically active secondary metabolites have been isolated and characterized from A. adenophora, some of them having inspired the research and development of new therapeutic agents. This review mainly focuses on biological properties of A. adenophora, including the toxicity, antibacterial, antifungal, insecticidal, antiviral activities and others. In addition, the current limits and potentials of A. adenophora and its extracts are also discussed.

8.
J Agric Food Chem ; 71(18): 7152-7162, 2023 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-37104842

RESUMEN

As chemical pesticides have caused serious environmental pollution, fungus-based biological control has become a developing alternative to chemical control. Here, we aimed to determine the molecular mechanism underlying how Metarhizium anisopliae facilitated invasive infection. We found that the fungus increased its virulence by downregulating glutathione S-transferase (GST) and superoxide dismutase (SOD) throughout termite bodies. Among 13 fungus-induced microRNAs throughout termite bodies, miR-7885-5p and miR-252b upregulation significantly downregulated several mRNAs in response to toxic substances to increase the fungal virulence [e.g., phosphoenolpyruvate carboxykinase (GTP) and heat shock protein homologue SSE1]. In addition, nanodelivered small interfering RNA of GST and SOD and miR-7885-5p and miR-252b mimics increased the virulence of the fungus. These findings provide new insights into the killing mechanism of entomopathogens and their utilization of the host miRNA machinery to reduce host defenses, laying the groundwork to enhance virulence of biocontrol agents for green pest management.


Asunto(s)
Isópteros , Metarhizium , MicroARNs , Animales , Isópteros/genética , Transcriptoma , Control Biológico de Vectores , Metarhizium/genética , MicroARNs/genética
9.
Int J Biol Macromol ; 226: 1154-1165, 2023 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-36427615

RESUMEN

Specificity and efficiency of plant virus transmission depend largely on protein-protein interactions of vectors and viruses. Cucurbit chlorotic yellows virus (CCYV), transmitted specifically by tobacco whitefly, Bemisia tabaci, in a semi-persistent manner, has caused serious damage on cucurbit and vegetable crops around the world. However, the molecular mechanism of interaction during CCYV retention and transmission are still lacking. CCYV was proven to bind particularly to the whitefly foregut, and here, we confirmed that the minor coat protein (CPm) of CCYV is participated in the interaction with the vector. In order to identify proteins of B. tabaci that interact directly with CPm of CCYV, the immunoprecipitation (IP) assay and DUALmembrane cDNA library screening technology were applied. The cytochrome c oxidase subunit 5A (COX), tubulin beta chain (TUB) and keratin, type I cytoskeletal 9-like (KRT) of B. tabaci shown strong interactions with CPm and are closely associated with the retention within the vector and transmission of CCYV. These findings on whitefly protein-CCYV CPm interactions are crucial for a much better understanding the mechanism of semi-persistent plant virus transmission by insect vectors, as well as for implement new strategies for effective management of plant viruses and their vector insects.


Asunto(s)
Crinivirus , Hemípteros , Animales , Cápside/metabolismo , Hemípteros/metabolismo , Virión , Proteínas de la Cápside/genética , Proteínas de la Cápside/metabolismo , Crinivirus/genética , Crinivirus/metabolismo , Enfermedades de las Plantas
10.
Molecules ; 27(6)2022 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-35335290

RESUMEN

Herein, a new Zn-MOF material, [Zn(L1)(L2)], 1, was built successfully through a one-pot solvothermal method. The 3D MOF structure was determined by Single X-ray diffraction analysis, IR, and elemental analysis. A series of PXRD tests of 1 after being immersed in different solvents and pH solutions demonstrated the good stability of 1. Interestingly, this material displayed high catalytic activity for the visible-light-driven hydrogen generation under the illumination of white LED in pure water or a mixture of DMF and H2O without additional photosensitizers and cocatalysts. Besides, the studies also showed that the catalytic activity changed constantly as well as the solvent ratio adjustment of DMF and H2O from 4:6 to 2:8. Additionally, the catalytic activity reached the best value (743 µmol g-1 h-1) when the solvent ratio was 4:6. The heterogeneous nature and recyclability of the MOF catalyst, as well as several factors that affect the catalytic activity, were investigated and described in detail. Moreover, the photocatalytic mechanism for the hydrogen generation of 1 was also proposed based on the fluorescence spectra and UV-vis absorption.

11.
J Am Chem Soc ; 143(42): 17587-17598, 2021 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-34644503

RESUMEN

Nanotubular materials have garnered considerable attention since the discovery of carbon nanotubes. Although the layer-to-tube rolling up mechanism has been well recognized in explaining the formation of many inorganic nanotubes, it has not been generally applied to coordination polymers (CPs). To uncover the key factors that determine the rolling-up of layered CPs, we have chosen the Co/R-, S-Xpemp [Xpemp = (4-X-1-phenylethylamino)methylphosphonic acid, X = H, F, Cl, Br] systems and study how the weak interactions influence the formation of layered or tubular structures. Four pairs of homochiral isostructural compounds R-, S-Co(Xpemp)(H2O)2 [X = H (1H), F (2F), Cl (3Cl), Br (4Br)] were obtained with tubular structures. The inclusion of 3,3'-azobipyridine (ABP) guest molecules led to compounds R-, S-[Co(Xpemp)(H2O)2]4·ABP·H2O with layered structures when X was Cl (5Cl) and Br (6Br), but tubular compounds 1H and 2F when X was H and F. Layered structures were also obtained for racemic compounds meso-Co(Xpemp)(H2O)2 [X = F (7F), Cl (8Cl), Br (9Br)] using racemic XpempH2 as the reaction precursor, but not when X = H. A detailed study on R-6Br revealed that layer-to-tube transformation occurred upon removal of ABP under hydrothermal conditions, forming R-4Br with a tubular structure. Similar layer-to-tube conversion did not occur in organic solvents. The results demonstrate that weak interlayer interactions are a prerequisite but not sufficient for the rolling-up of the layers. In the present cases, water also provides a driving force in the layer-to-tube transformation. The experimental results were rationalized by theoretical calculations.

12.
Cancer Lett ; 493: 120-127, 2020 11 28.
Artículo en Inglés | MEDLINE | ID: mdl-32829006

RESUMEN

LIM kinase 1 (LIMK1) and p21-activated kinase 4 (PAK4) are often over-expressed in breast tumors, which causes aggressive cancer phenotypes and unfavorable clinical outcomes. In addition to the well-defined role in regulating cell division, proliferation and invasion, the two kinases promote activation of the MAPK pathway and cause endocrine resistance through phosphorylating estrogen receptor alpha (ERα). PAK4 specifically phosphorylates LIMK1 and its functional partners, indicating possible value of suppressing both kinases in cancers that over-express PAK4 and/or LIMK1. Here, for the first time, we assessed the impact of combining LIMK1 inhibitor LIMKi 3 and PAK4 inhibitor PF-3758309 in preclinical breast cancer models. LIMK1 and PAK4 pharmacological inhibition synergistically reduced the survival of various cancer cell lines, exhibiting specific efficacy in luminal and HER2-enriched models, and suppressed development and ERα-driven signals in a BT474 xenograft model. In silico analysis demonstrated the cell lines with reliance on LIMK1 were the most prone to be susceptible to PAK4 inhibition. Double LIMK1 and PAK4 targeting therapy can be a successful therapeutic strategy for breast cancer, with a unique efficiency in the subtypes of luminal and HER2-enriched tumors.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Quinasas Lim/metabolismo , Pirazoles/administración & dosificación , Pirroles/administración & dosificación , Tiazoles/administración & dosificación , Quinasas p21 Activadas/metabolismo , Animales , Neoplasias de la Mama/metabolismo , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Sinergismo Farmacológico , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Quinasas Lim/antagonistas & inhibidores , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Ratones , Fosforilación/efectos de los fármacos , Pirazoles/farmacología , Pirroles/farmacología , Tiazoles/farmacología , Ensayos Antitumor por Modelo de Xenoinjerto , Quinasas p21 Activadas/antagonistas & inhibidores
13.
ACS Omega ; 5(23): 13770-13776, 2020 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-32566842

RESUMEN

Retinal (C20) and the C25 and C30 homologues were compared as radical scavengers together with their C22, C27, and C32 homologues linked with daidzein through a B'3 (isoflavonoid) to oxo-carbon (aldehyde) covalent bond. Oxidation potential in acetonitrile determined by cyclic voltammetry and ionization potential calculated by density functional theory for the aldehydes and dyads (conjugates), of which the two longer are new, decreased linearly with the wavenumber for absorption maximum. The logarithm of the second-order rate constant for scavenging of the ABTS•+ increased linearly with decreasing oxidation potential suggesting that longer conjugation in the antioxidant increases the rate of electron transfer. A similar linear free energy relationship was found for the rate of scavenging DPPH•, including daidzein, which may indicate involvement of hydrogen atom transfer from an isoflavonoid phenol. Prediction of radical scavenging efficiency from visible absorption spectra was demonstrated with the perspective of rational design of bifunctional amphiphilic antioxidants.

14.
Regen Biomater ; 7(1): 99-107, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32440361

RESUMEN

Scar formation seriously affects the repair of damaged skin especially in adults and the excessive inflammation has been considered as the reason. The self-assembled peptide-hydrogels are ideal biomaterials for skin wound healing due to their similar nanostructure to natural extracellular matrix, hydration environment and serving as drug delivery systems. In our study, resveratrol, a polyphenol compound with anti-inflammatory effect, is loaded into peptide-hydrogel (Fmoc-FFGGRGD) to form a wound dressing (Pep/RES). Resveratrol is slowly released from the hydrogel in situ, and the release amount is controlled by the loading amount. The in vitro cell experiments demonstrate that the Pep/RES has no cytotoxicity and can inhibit the production of pro-inflammatory cytokines of macrophages. The Pep/RES hydrogels are used as wound dressings in rat skin damage model. The results suggest that the Pep/RES dressing can accelerate wound healing rate, exhibit well-organized collagen deposition, reduce inflammation and eventually prevent scar formation. The Pep/RES hydrogels supply a potential product to develop new skin wound dressings for the therapy of skin damage.

15.
J Pharmacol Exp Ther ; 373(2): 248-260, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32165443

RESUMEN

It has been identified that arginine vasopressin (AVP), vasopressin receptor 2(V2R), and the aquaporin 2 (AQP2) signaling pathway in the inner ear play important roles in hearing and balance functions through regulating the endolymph equilibrium; however, the contributions of this signaling pathway to the development of motion sickness are unclear. The present study was designed to investigate whether the activation of the AVP-V2R-AQP2 signaling pathway in the inner ear is involved in the induction of motion sickness and whether mozavaptan, a V2R antagonist, could reduce motion sickness. We found that both rotatory stimulus and intraperitoneal AVP injection induced conditioned taste aversion (a confirmed behavioral index for motion sickness) in rats and activated the AVP-V2R-AQP2 signaling pathway with a responsive V2R downregulation in the inner ears, and AVP perfusion in cultured epithelial cells from rat endolymphatic sacs induced similar changes in this pathway signaling. Vestibular training, V2R antagonist mozavaptan, or PKA inhibitor H89 blunted these changes in the V2R-AQP2 pathway signaling while reducing rotatory stimulus- or DDAVP (a V2R agonist)-induced motion sickness in rats and dogs. Therefore, our results suggest that activation of the inner ear AVP-V2R-AQP2 signaling pathway is potentially involved in the development of motion sickness; thus, mozavaptan targeting AVP V2Rs in the inner ear may provide us with a new application option to reduce motion sickness. SIGNIFICANCE STATEMENT: Motion sickness affects many people traveling or working. In the present study our results showed that activation of the inner ear arginine vasopressin-vaspopressin receptor 2 (V2R)-aquaporin 2 signaling pathway was potentially involved in the development of motion sickness and that blocking V2R with mozavaptan, a V2R antagonist, was much more effective in reducing motion sickness in both rat and dog; therefore, we demonstrated a new mechanism to underlie motion sickness and a new candidate drug to reduce motion sickness.


Asunto(s)
Acuaporina 2/fisiología , Arginina Vasopresina/fisiología , Oído Interno/fisiología , Mareo por Movimiento/etiología , Receptores de Vasopresinas/fisiología , Animales , Antagonistas de los Receptores de Hormonas Antidiuréticas/uso terapéutico , Arginina Vasopresina/sangre , Benzazepinas/uso terapéutico , Células Cultivadas , Proteínas Quinasas Dependientes de AMP Cíclico/antagonistas & inhibidores , Perros , Femenino , Masculino , Mareo por Movimiento/tratamiento farmacológico , Ratas , Ratas Sprague-Dawley , Transducción de Señal/fisiología
16.
Nat Commun ; 10(1): 3368, 2019 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-31358761

RESUMEN

For seeking high enantiopurity, the previously reported thermal asymmetric catalysis is usually carried out at low temperature sometimes with limited yield, that is, the high enantiomeric excess (ee) usually at the cost of high yield. Thus, the achieving both high stereoselectivity and yield is an enormous challenge. We report herein two metal nanoparticle (M NP)-loaded and porphyrin-containing homochiral covalent organic framework (CCOF)-based composite catalysts, and their application in the thermally-driven asymmetric one-pot Henry and A3-coupling reactions. All the reactions are conducted at elevated temperatures with both excellent stereoselectivity and yield which resulted from the synergy of CCOF confinement effect and M NP catalytic activation. Notably, the needed thermal energy for the asymmetric reactions herein is derived from the photothermal conversion via porphyrin-based CCOF upon irradiation with visible light. Remarkably, the CCOF confinement effect can be effectively maintained up to 100 °C for the asymmetric one-pot Henry and A3-coupling reactions herein.

17.
Inorg Chem ; 58(14): 9253-9259, 2019 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-31247830

RESUMEN

A new homochiral BINAPDA-Zr-MOF was prepared by a new chiral organic linker of (R)-4,4'-(6,6'-dichloro-2,2'-diethoxyl-[1,1'-binaphthalene]-4,4'-diyl)dibenzoic acid (R-L) and ZrCl4 under solvothermal conditions. Its structure was determined by Pawley refinement on the basis of the measured PXRD pattern determined for BINAPDA-Zr-MOF, and it showed that the obtained chiral MOF crystallized in the F23 space group with the same topological structure as that of UiO-66. The obtained BINAPDA-Zr-MOF can be a very active catalyst to catalyze aldehyde cyanosilylation. In addition, the chiral BINAPDA-Zr-MOF was a typical solid catalyst, which was proved by a hot leaching test; moreover, it could be reused at least five times without loss of its catalytic activity and enantioselectivity.

18.
Cell Death Dis ; 10(4): 252, 2019 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-30874550

RESUMEN

Diffuse large B cell lymphoma (DLBCL) is a common and fatal hematological malignancy. Long noncoding RNAs (lncRNAs) have emerged as crucial biomarkers and regulators in many cancers. Novel lncRNA biomarker in DLBCL needs to be investigated badly, as well as its function and molecular mechanism. To further explore, microarray analysis was performed to identify the differentially expressed lncRNAs in DLBCL tissues. To investigate the biological functions of SMAD5-AS1, we performed gain- and loss-of-function experiments in vitro and in vivo. Furthermore, bioinformatics analysis, dual-luciferase reporter assays, Argonaute 2-RNA immunoprecipitation (AGO2-RIP), RNA pull-down assay, quantitative PCR arrays, western blot assay, TOPFlash/FOPFlash reporter assay, and rescue experiments were conducted to explore the underlying mechanisms of competitive endogenous RNAs (ceRNAs). We found that SMAD5-AS1 was down-regulated in DLBCL tissues and cell lines. Functionally, SMAD5-AS1 downregulation promoted cell proliferation in vitro and in vivo, whereas SMAD5-AS1 overexpression could lead to the opposite effects in vitro and in vivo. Bioinformatics analysis and luciferase assays revealed that miR-135b-5p was a direct target of SMAD5-AS1, which was validated by dual-luciferase reporter assays, AGO2-RIP, RNA pull-down assay, and rescue experiments. Also, dual-luciferase reporter assays and rescue experiments demonstrated that miR-135b-5p targeted the adenomatous polyposis coli (APC) gene directly. SMAD5-AS1/miR-135b-5p inhibits the cell proliferation via inactivating the classic Wnt/ß-catenin pathway in the form of APC dependency. Our results indicated that SMAD5-AS1 inhibits DLBCL proliferation by sponging miR-135b-5p to up-regulate APC expression and inactivate classic Wnt/ß-catenin pathway, suggesting that SMAD5-AS1 may act as a potential biomarker and therapeutic target for DLBCL.


Asunto(s)
Poliposis Adenomatosa del Colon/metabolismo , Linfoma de Células B Grandes Difuso/metabolismo , MicroARNs/metabolismo , ARN Largo no Codificante/genética , Vía de Señalización Wnt/genética , beta Catenina/metabolismo , Poliposis Adenomatosa del Colon/genética , Animales , Apoptosis/genética , Proteínas Argonautas/genética , Proteínas Argonautas/metabolismo , Proliferación Celular/genética , Regulación hacia Abajo , Regulación Neoplásica de la Expresión Génica , Células HEK293 , Humanos , Linfoma de Células B Grandes Difuso/genética , Ratones Endogámicos BALB C , Ratones Desnudos , MicroARNs/genética , Trasplante Heterólogo , Regulación hacia Arriba , beta Catenina/genética
19.
Int J Med Sci ; 15(13): 1458-1465, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30443165

RESUMEN

Aseptic loosening is the most common complication of joint replacement. Previous studies showed that acrylic bone cement loaded with a commercially-available alendronate powder (APAC) had good promise against wear debris-mediated osteolysis for prevention of aseptic loosening. The purpose of the present study was to investigate the effect of adding alendronate powder to an acrylic bone cement on quasi-static mechanical properties (namely, compressive strength, compressive modulus, tensile strength, and flexural strength), fatigue life, porosity, and microstructure of the cement. The results showed that adding up to 1 wt./wt.% alendronate powder exerted no detrimental effect on any of the quasi-static mechanical properties. However, the fatigue life of APAC decreased by between ~17% and ~27 % and its porosity increased by between ~ 5-7 times compared with corresponding values for the control cement (no alendronate powder added). Fatigue life was negatively and significantly correlated with porosity. Considering that fatigue life of the cement plays a significant role in joint replacement survival, clinical use of APAC cannot be recommended.


Asunto(s)
Alendronato/química , Polimetil Metacrilato/química , Fatiga , Humanos , Porosidad
20.
Life Sci ; 209: 409-419, 2018 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-30096387

RESUMEN

AIMS: Postmenopausal osteoporosis is a bone metabolism disease that is caused by an imbalance between bone-resorbing osteoclast and bone-forming osteoblast actions. Herein, we describe the role of troxerutin (TRX), a trihydroxyethylated derivative of rutin, in ovariectomy (OVX)-induced osteoporosis and its effects on the regulation of osteoclasts and osteoblasts. MAIN METHODS: In vivo, OVX female mice were intraperitoneally injected with either saline, 50 mg/kg TRX, or 150 mg/kg TRX for 6 weeks and then sacrificed for micro-computed tomography analyses, histological analyses, and biomechanical testing. In vitro, RAW264.7 cell-derived osteoclasts and MC3T3-E1 cell-derived osteoblasts were treated with different concentrations of TRX to examine the effect of TRX on osteoclastogenesis and bone resorption, as well as on osteogenesis and mineralization. KEY FINDINGS: In this study, we demonstrated that TRX prevented cortical and trabecular bone loss in ovariectomized mice by reducing osteoclastogenesis and promoting osteogenesis in vivo. In vitro, TRX inhibited the formation and activity of RAW264.7-derived osteoclasts and the expression of nuclear factor of activated T-cells 1 and cathepsin K. Meanwhile, TRX improved the osteogenesis and mineralization of MC3T3-E1 by enhancing the expression of Runt-related transcription factor 2, Osterix, and collagen type 1 alpha 1. SIGNIFICANCE: Our data demonstrated that TRX could prevent OVX-induced osteoporosis and be used in a novel treatment for postmenopausal osteoporosis.


Asunto(s)
Anticoagulantes/farmacología , Resorción Ósea/tratamiento farmacológico , Hidroxietilrutósido/análogos & derivados , Osteogénesis/efectos de los fármacos , Osteoporosis Posmenopáusica/tratamiento farmacológico , Sustancias Protectoras/farmacología , Animales , Resorción Ósea/etiología , Resorción Ósea/patología , Diferenciación Celular/efectos de los fármacos , Femenino , Humanos , Hidroxietilrutósido/farmacología , Ratones , Ratones Endogámicos C57BL , Osteoblastos/citología , Osteoblastos/efectos de los fármacos , Osteoclastos/citología , Osteoclastos/efectos de los fármacos , Osteoporosis Posmenopáusica/etiología , Osteoporosis Posmenopáusica/patología , Ovariectomía/efectos adversos , Células RAW 264.7
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA