Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.766
Filtrar
1.
ACS Nano ; 2021 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-33939408

RESUMEN

Exploring the advanced oxygen evolution reaction (OER) electrocatalysts is highly desirable toward sustainable energy conversion and storage, yet improved efficiency in acidic media is largely hindered by its sluggish reaction kinetics. Herein, we rationally manipulate the electronic states of the strongly electron correlated pyrochlore ruthenate Y2Ru2O7 alternative through partial A-site substitution of Sr2+ for Y3+, efficiently improving its intrinsic OER activity. The optimized Y1.7Sr0.3Ru2O7 candidate observes a highly intrinsic mass activity of 1018 A gRu-1 at an overpotential of 300 mV with excellent durability in 0.5 M H2SO4 electrolyte. Combining synchrotron-radiation X-ray spectroscopic investigations with theoretical simulations, we reveal that the electron correlations in the Ru 4d band are weakened through coordinatively geometric regulation and charge redistribution by the exotic Sr2+ cation, enabling the delocalization of Ru 4d electrons via an insulator-to-metal transition. The induced Ru-O covalency promotion and band alignment rearrangement decreases the charge transfer energy to accelerate interfacial charge transfer kinetics. Meanwhile, the chemical affinity of oxygen intermediates is also rationalized to weaken the metal-oxygen binding strength, thus lowering the energy barrier of the overall reaction. This work offers fresh insights into designing advanced solid-state electrocatalysts and underlines the versatility of electronic structure manipulation in tuning catalytic activity.

2.
Hum Vaccin Immunother ; : 1-10, 2021 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-33950775

RESUMEN

Vaccination programs are cost-effective for preventing communicable diseases, yet vaccine events caused vaccine crises among parents nationwide, which has created challenges for current and future vaccination programs. This study aimed to investigate parents' emotional reactions (i.e., anger and anxiety) toward the 2018 vaccine event in China and explore the associations between parental emotional reactions and vaccine decision-making. A cross-sectional survey was conducted among 1,135 parents in 2018. Five-point Likert scales were provided for respondents to rank their anger and anxiety toward the event, and their vaccine-related trust and intentions before and after the event. Multiple logistic regression analyses were employed to explore the associations. Regarding the vaccine event, 576 (50.8%) and 402 (35.4%) respondents felt very angry and angry, and 310 (27.4%) and 516 (45.5%) respondents felt very anxious and anxious, respectively. Altogether, 797 (70.3%) respondents reported a lower trust in domestically produced vaccines after the event, and 704 (62.3%) respondents reported declines in intention to choose domestically produced vaccines for their children. Multiple logistic regression analyses revealed that anxiety was a predictor of lower trust and intention after the event (p < .001), anger was a predictor of lower trust (p = .005), and both were risk factors for declines in trust and intention (p < .01). This study confirmed that negative emotional reactions toward a vaccine event were important contributors for parental vaccine decisions. Health authorities and facilities are encouraged to act in a timely manner to reduce the public's negative emotions by providing rapid crisis responses.

3.
Artículo en Inglés | MEDLINE | ID: mdl-33937955

RESUMEN

PURPOSE: Severe left atrial spontaneous echo contrast (SLASEC) is considered the prior stage to thrombosis and a high-risk factor for thrombotic events. Studies have suggested an effect of D-dimer blood concentration on exclusion of left atrial thrombus (LAT), but it remains unclear whether D-dimer concentrations differ between atrial fibrillation (AF) patients with SLASEC or LAT. METHODS: Nonvalvular AF patients scheduled to undergo catheter ablation or cardioversion in Shanghai Ruijin Hospital between January 2017 and July 2020 were screened for this prospective study. All patients underwent transesophageal echocardiography (TEE) to detect SLASEC or LAT. D-dimer concentrations were measured at the time of TEE. Clinical data including CHA2DS2-VASc score were evaluated. Major complications with thromboembolism in the SLASEC group were followed up at least 6 months after therapy. RESULTS: Among 920 consecutively enrolled nonvalvular AF patients, 30 patients with SEC grade 0, 35 patients with SLASEC, and 22 patients with LAT were included. D-dimer concentration and CHA2DS2-VASc score were significantly lower in the SLASEC group compared with the LAT group (D-dimer, 0.26±0.13 vs. 0.86±0.9 mg/L, P<0.05; CHA2DS2-VASc score, 2.3±0.9 vs. 3.1±1.5, P=0.02). The cut-off value for D-dimer concentration (0.285 mg/L) had sensitivity of 77.3% and specificity of 80.0% for prediction of LAT. D-dimer concentration showed a decreasing trend with a significant difference (0.42±0.22 vs. 0.33±0.18 mg/L, P=0.03) for 9 patients in the LAT group after complete thrombus resolution by anticoagulation treatment. No major or fatal bleeding, ischemic stroke, or systemic thromboembolism events occurred in the SLASEC group during the 6-month follow-up. CONCLUSIONS: This study demonstrated a significantly lower D-dimer concentration and CHA2DS2-VASc score in AF patients with SLASEC than in those with LAT. The D-dimer cut-off value (0.285 mg/L) can be used as an effective reference index to distinguish the pre-thrombotic state of LAT from LAT. D-dimer blood concentration may be a predictor of LAT thrombolysis.

4.
Stem Cell Res Ther ; 12(1): 257, 2021 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-33933157

RESUMEN

BACKGROUND: Cutaneous wound healing and regeneration have become a recognized health challenge in the world, which causes severe damage to the mental and physical health of patients. Human adipose-derived mesenchymal stem cells (hADSC) play an essential role in wound healing via their paracrine function. Exosomes secreted by hADSC may contribute to this progress. In this study, we investigated the potential clinical application roles of hADSC and hADSC-derived exosomes (hADSC-Exo) in cutaneous wound healing. METHODS: hADSC-Exo was isolated from human hADSC by ultracentrifugation. Mice were subjected to a full-thickness skin biopsy experiment and treated with either control vehicle or hADSC or hADSC-Exo by smearing administration (sm) or subcutaneous administration (sc) or intravenous administration (iv). The efficacy of hADSC and hADSC-Exo on wound healing was evaluated by measuring wound closure rates, histological analysis. RESULTS: Combined application of local hADSC-Exo smearing and hADSC/hADSC-Exo intravenous administration offered the additional benefit of promoting wound healing, accelerating re-epithelialization, reducing scar widths, and enhancing angiogenesis and collagen synthesis. Either topical application of hADSC-Exo or systemic administration with hADSC/hADSC-Exo appeared more effective in stimulating cell proliferation, inhibiting cell apoptosis and inflammation, and promoting skin elasticity and barrier integrity, with increased genes expression of PCNA, VEGF, collagen III, Filaggrin, Loricrin, and AQP3, with decreased genes expression of TNF-alpha. CONCLUSION: Our findings suggest that the combined administration of hADSC/hADSC-Exo can facilitate cutaneous wound healing and reduce scar formation. These data provide the first evidence for the feasibility of smearing of hADSC-Exo as a cell-free therapy in treating cutaneous wounds, and the potential clinical value of combined administration of hADSC/hADSC-Exo.

5.
Colloids Surf B Biointerfaces ; 204: 111790, 2021 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-33932887

RESUMEN

In past decades, to improve the chemotherapeutic efficiency and reduce the systemic toxicity of small molecule anti-cancer drugs, polymer-based drug delivery systems (DDSs) have attracted great attention for tumor treatment due to their remarkable biocompatibility and responsive degradation in tumor microenvironment (TME). Herein, we developed a kind of pH-responsive and degradable hyperbranched polymeric nanocarriers via yne-phenol click-reaction of resveratrol (RSV) with bifunctional n-butyl dipropiolate (BDP) for efficient doxorubicin (DOX) delivery. The natural product RSV with three phenol groups has excellent antioxidant activity and synergetic enhancement for some anticancer drugs such as DOX. RSV tends to attack the alkynyl groups on BDP by nucleophilic addition in the presence of base as catalyst to afford hyperbranched polyprodrug (denoted as RB). PEGylated RB (termed as RBP) were further synthesized to improve the water solubility and prolong blood circulation by the click reaction of propiolate-terminated RB with amino terminated poly(ethylene glycol) (PEG-NH2). Interestingly, the RBP have high DOX loading ratio (∼58.6 %) at neutral pH, but the vinyl-ether bonds in RB could break down at low pH conditions such as acidic TME (extracellular pH∼6.8, endosomes and lysosomes pH∼5.0) that leading to the targeting release of DOX and RSV. Therefore, the developed RBP@DOX nanoparticles exhibited high kill efficiency to tumor cells and slight damage to normal cells due to the effective delivery and release of DOX and RSV in tumor sites and the synergistic enhancement effect of two drugs.

6.
Food Chem ; 358: 129898, 2021 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-33933961

RESUMEN

The sensitive detection of pesticides in complex environment is important but still challenging in presence of organic-rich water sample and food matrix. Herein, we reported a nitrile-mediated SERS immunosensor for sensitive and optical anti-interference determination of imidacloprid. Raman tag contained CN bond could provide a sharp characteristic peak in the Raman-silent spectral window (1800 ~ 2800 cm-1), which could resist the optical noises from the fingerprint region (<1800 cm-1). Aucore-Agshell bimetallic nanocuboid (AuNR@Ag) connected with antigen and Raman tag was used as Raman probe, while Fe3O4 magnetic nanoparticle functionalized with anti-imidacloprid antibody was applied as signal enhancer. Owing to the specific recognition ability between antigen and antibody, the competitive system with imidacloprid was formed. Under the optimal condition, the linear relationship was developed in the range of 10-400 nM. Finally, the SERS immunosensor was successfully applied to determine imidacloprid in real samples with recoveries from 96.8% to 100.5%.

7.
PLoS One ; 16(4): e0250526, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33891649

RESUMEN

INTRODUCTION: The equity of health resource allocation geographically is a contested topic. Sichuan Province, located in Southwest China, has varied topography, providing us with natural materials to explore the determinants of health resource distribution. MATERIALS AND METHODS: Spatial panel econometric models were constructed to explore the relationship between health resources and factors such as health care service demand and socioeconomic and demographic perspectives using data from Sichuan Province for eight consecutive years (2010-2017). RESULTS: Health care service demands were found to be a major driving force behind the distribution of health resources, showing that an increase in health care service demands draws health resources to specific counties and surrounding areas. From a socioeconomic perspective, gross domestic product per capita and the average wage show a positive association with health resources. In addition, the total population and proportion of the urban population have diverse effects in regard to health-related human resources but have the same effects on material and financial health resources. CONCLUSIONS: Our results provide the Chinese government with evidence needed to formulate and promulgate effective policies, especially those aiming to tackle inequity among different regions.

8.
Ann Palliat Med ; 2021 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-33894737

RESUMEN

Vascular calcification (VC) has been proved the main pathophysiology basis that results in the cardiovascular disease which become the leading cause of death in patients with chronic kidney disease. The disordered mineral metabolism, hyperphosphatemia, overuse of calcium binders, occurred in the setting of uremia, have become the critical risk factors of vascular calcification in chronic kidney disease, in which the vascular smooth muscle cells undergo differentiation to osteoblast-like cells. The mechanisms involved in vascular calcification are complicated and exosomes, as novel players, are proven to play a vital role in VC and function as initializers for mineral deposition. Exosomal miRNAs play an important role in the regulation of cellular functions in vascular calcification. In this review, we focused on the roles of exosomes during VC, especially on their effects on regulating vascular calcification through initializing mineral deposition as a nidus, transporting microRNAs to the recipient cells and mediating the vascular smooth muscle cells differentiation to osteoblast-like cells.

9.
Nat Microbiol ; 6(5): 540-548, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33903746

RESUMEN

The identification and proper naming of microfungi, in particular plant, animal and human pathogens, remains challenging. Molecular identification is becoming the default approach for many fungal groups, and environmental metabarcoding is contributing an increasing amount of sequence data documenting fungal diversity on a global scale. This includes lineages represented only by sequence data. At present, these taxa cannot be formally described under the current nomenclature rules. By considering approaches used in bacterial taxonomy, we propose solutions for the nomenclature of taxa known only from sequences to facilitate consistent reporting and communication in the literature and public sequence repositories.

10.
Chem Commun (Camb) ; 57(35): 4319-4322, 2021 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-33913950

RESUMEN

We demonstrate that the capacity decay and voltage drop issues of the Li3V2(PO4)3 cathode are significantly addressed by using a concentrated aqueous electrolyte based on Zn and Li salts. The resultant aqueous Zn//Li3V2(PO4)3 battery achieves a high output voltage of 1.75 V and a long lifespan with 82.3% capacity retention over 2000 cycles. Joint structural and spectroscopic characterizations reveal that this battery operates through Li+ (de)intercalation into the cathode along with Zn2+ plating/stripping at the anode.

11.
Front Immunol ; 12: 648913, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33912173

RESUMEN

The excessive M1 polarization of macrophages drives the occurrence and development of inflammatory diseases. The reprogramming of macrophages from M1 to M2 can be achieved by targeting metabolic events. Taurine promotes for the balance of energy metabolism and the repair of inflammatory injury, preventing chronic diseases and complications. However, little is known about the mechanisms underlying the action of taurine modulating the macrophage polarization phenotype. In this study, we constructed a low-dose LPS/IFN-γ-induced M1 polarization model to simulate a low-grade pro-inflammatory process. Our results indicate that the taurine transporter TauT/SlC6A6 is upregulated at the transcriptional level during M1 macrophage polarization. The nutrient uptake signal on the membrane supports the high abundance of taurine in macrophages after taurine supplementation, which weakens the status of methionine metabolism, resulting in insufficient S-adenosylmethionine (SAM). The low availability of SAM is directly sensed by LCMT-1 and PME-1, hindering PP2Ac methylation. PP2Ac methylation was found to be necessary for M1 polarization, including the positive regulation of VDAC1 and PINK1. Furthermore, its activation was found to promote the elimination of mitochondria by macrophages via the mitophagy pathway for metabolic adaptation. Mechanistically, taurine inhibits SAM-dependent PP2Ac methylation to block PINK1-mediated mitophagy flux, thereby maintaining a high mitochondrial density, which ultimately hinders the conversion of energy metabolism to glycolysis required for M1. Our findings reveal a novel mechanism of taurine-coupled M1 macrophage energy metabolism, providing novel insights into the occurrence and prevention of low-grade inflammation, and propose that the sensing of taurine and SAM availability may allow communication to inflammatory response in macrophages.

12.
Artículo en Inglés | MEDLINE | ID: mdl-33885287

RESUMEN

The rational design of a hollow heterostructure promotes the development of highly durable anode materials for lithium-ion batteries. Herein, carbon-confined MoO2/Sn/NC@NC heterostructured nanotubes evolving from MoO3 nanorods have been successfully synthesized for the first time. In the growth of the Mo/Sn precursor, a peculiar microstructure evolution occurs from solid rods to hollow tubes through a solid-liquid reaction. The MoO2/Sn composite is restricted within the double carbon layer after subsequent annealing and carbonization that distinctly inherits the morphology of the Mo/Sn precursor. The resulting electrode shows good capacities with hardly any attenuation (925.4 mA h g-1 after 100 cycles at 100 mA g-1) and excellent long cycle life (620.1 mA h g-1 after 1000 cycles at 2 A g-1). The MoO2/Sn/NC@NC nanotubes contain the synergistic effect, elaborate core-shell structure, large specific surface areas, and abundant voids. These superiorities not only provide beneficial channels for the electrolyte to fully come into contact with electrode materials and more active sites for redox reactions but also effectively alleviate the volume fluctuation and sustain the electrical connectivity to retain a stable solid-electrolyte interface layer, indeed, bringing about the prominent Li-storage performance. The present study paves a feasible avenue to prepare core-shell structures with high reversible capacity and long-term cycle performance for energy storage devices.

13.
J Econ Entomol ; 2021 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-33885770

RESUMEN

The insecticides of microbial origin may be promising biocontrol agents to control pests. In this study, a major metabolite was extracted and purified from Serratia marcescens KH-001 and identified as prodigiosin with a molecule weight of 324.2094, and our primary aim was to evaluate the effects of prodigiosin against Diaphorina citri Kuwayama (Hemiptera: Liviidae) in the laboratory and in the field. Toxicity of purified prodigiosin to nymphs increased with increasing temperature from 25 to 35°C. The laboratory experiment results observed inhibition effects of purified prodigiosin at LC50 on oviposition and egg hatch of D. citri at 30°C. Furthermore, adults that fed on citrus leaves treated with LC20 and LC50 solution of purified prodigiosin at 30°C excreted less honeydew (28-35%) compared with controls, suggesting moderate antifeedant activity of prodigiosin. The results of field experiment showed that 10% prodigiosin emulsifiable concentrate exhibited better control efficacy (70-100%) at three concentrations (100, 200, and 500 mg/liter) in July and August than in October. These data indicate that prodigiosin will be a highly effective compound for the control of D. citri depending on the prevailing temperature conditions and may become a commercially available product to be widely used in citrus orchards.

14.
Stem Cell Res Ther ; 12(1): 239, 2021 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-33853670

RESUMEN

Adipose-derived stem cell (ADSC) is one of the most widely used candidate cell for intervertebral disc (IVD) degeneration-related disease. However, the poor survival and low differentiation efficacy in stressed host microenvironment limit the therapeutic effects of ADSC-based therapy. The preconditioning has been found effective to boost the proliferation and the functioning of stem cells in varying pathological condition. Lithium is a common anti-depression drug and has been proved effective to enhance stem cell functioning. In this study, the effects of preconditioning using LiCl on the cellular behavior of ADSC was investigated, and specially in a degenerative IVD-like condition. METHOD: The cellular toxicity on rat ADSC was assessed by detecting lactate dehydrogenase (LDH) production after treatment with a varying concentration of lithium chloride (LiCl). The proliferative capacity of ADSC was determined by detecting Ki67 expression and the relative cell number of ADSC. Then, the preconditioned ADSC was challenged by a degenerative IVD-like condition. And the cell viability as well as the nucleus pulpous (NP) cell differentiation efficacy of preconditioned ADSC was evaluated by detecting the major marker expression and extracellular matrix (ECM) deposit. The therapeutic effects of preconditioned ADSC were evaluated using an IVD degeneration rat model, and the NP morphology and ECM content were assessed. RESULTS: A concentration range of 1-10 mmol/L of LiCl was applied in the following study, since a higher concentration of LiCl causes a major cell death (about 40%). The relative cell number was similar between preconditioned groups and the control group after preconditioning. The Ki67 expression was elevated after preconditioning. Consistently, the preconditioned ADSC showed stronger proliferation capacity. Besides, the preconditioned groups exhibit higher expression of NP markers than the control group after NP cell induction. Moreover, the preconditioning of LiCl reduced the cell death and promoted ECM deposits, when challenged with a degenerative IVD-like culture. Mechanically, the preconditioning of LiCl induced an increased cellular reactive oxidative species (ROS) level and activation of ERK1/2, which was found closely related to the enhanced cell survival and ECM deposits after preconditioning. The treatment with preconditioned ADSC showed better therapeutic effects than control ADSC transplantation, with better NP preservation and ECM deposits. CONCLUSION: These results suggest that the preconditioning with a medium level of LiCl boosts the cell proliferation and differentiation efficacy under a normal or hostile culture condition via the activation of cellular ROS/ERK axis. It is a promising pre-treatment of ADSC to promote the cell functioning and the following regenerative capacity, with superior therapeutic effects than untreated ADSC transplantation.

15.
Virol J ; 18(1): 79, 2021 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-33858464

RESUMEN

BACKGROUND: Raccoon dog parvovirus (RDPV) causes acute infectious diseases in raccoon dogs and may cause death in severe cases. The current treatment strategy relies on the extensive usage of classical inactivated vaccine which is marred by large doses, short immunization cycles and safety concerns. METHODS: The present study aimed at optimization of RDPV VP2 gene, subcloning the gene into plasmid pET30a, and its subsequent transfer to Escherichia coli with trigger factor 16 for co-expression. The protein thus expressed was purified with ammonium sulfate precipitation, hydrophobic chromatography, and endotoxin extraction procedures. VLPs were examined by transmission electron microscopy, dynamic light scattering, and the efficacy of VLPs vaccine was tested in vivo. RESULTS: Results indicated that RDPV VP2 protein could be expressed soluble. Transmission electron microscopy and dynamic light scattering results indicated that RDPV VP2 self-assembled into VLPs. Hemagglutination inhibition antibody titers elicited by Al(OH)3 adjuvanted RDPV VLPs were comparable with RDPV inactivated vaccines, and the viral loads in the blood of the struck raccoon dogs were greatly reduced. Hematoxylin and eosin and Immunohistochemical results indicated that RDPV VLPs vaccine could protect raccoon dogs against RDPV infections. CONCLUSIONS: These results suggest that RDPV VLPs can become a potential vaccine candidate for RDPV therapy.

16.
Artículo en Inglés | MEDLINE | ID: mdl-33877733

RESUMEN

As a new class of crystalline porous organic materials, covalent organic frameworks (COFs) have attracted considerable attention in proton conduction due to their regular channels and tailored functionality. However, most COFs are insoluble and unprocessable, which makes the membrane preparation for practical usage a challenge. Herein, we employed surface-initiated condensation polymerization of trialdehyde and phenylenediamine in the synthesis of sulfonic COF (SCOF) coatings. The COF layer thickness can be finely tuned from ten to one hundred nanometers by controlling the polymerization time. Moreover, free-standing COF membranes were facilely obtained by sacrificing the bridging layer without any decomposition of the COF structure. Benefiting from the abundant sulfonic acid groups in the COF channels, the proton conductivity of SCOF membrane reached to 0.54 S cm -1 at 80 °C in pure water. To our knowledge, this is one of the highest values for pristine COF membrane in the absence of additional additives. Our approach would pave the way for the potential application of COF materials in proton conducting membranes.

17.
Psychiatry Res ; 299: 113892, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33799125

RESUMEN

Attention Bias Modification (ABM) is a novel computerized therapy for anxiety disorders and is thought to augment the effect of Cognitive Behavior Therapy (CBT) as it may target different mechanisms. Recently, a growing number of studies have examined the combined effects of ABM and CBT on clinically anxious patients, with mixed results. This review examined the combined efficacy of ABM and CBT. A literature search was conducted in four main databases: PsycINFO, Embase, Pubmed and the Cochrane library, resulting in 11 randomized studies. The combination of ABM and CBT had small but significant effects on clinician-rated anxiety symptoms and attention bias towards threat compared to the control group, while ESs for anxiety (all measures), self-reported or parent-reported anxiety measures and depression symptoms were non-significant. Studies in which ABM was conducted as an integral part of each CBT session yielded greater reduction in anxiety symptoms than those conducting ABM and CBT at separate time points. Older participants and patients with social anxiety disorder tended to benefit less from the combination of ABM and CBT based on bias scores. This study may provide preliminary evidence that ABM and CBT have the potential to complement each other, especially when they are conducted integrally.

18.
Mol Metab ; 51: 101230, 2021 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-33823318

RESUMEN

OBJECTIVE: Adaptive rewiring of cancer energy metabolism has received increasing attention. By binding with LDLs, LDLRs make most of the circulating cholesterol available for cells to utilize. However, it remains unclear how LDLR works in HCC development by affecting cholesterol metabolism. METHODS: Database analyses and immunohistochemical staining were used to identify the clinical significance of LDLR in HCC. A transcriptome analysis was used to reveal the mechanism of LDLR aberration in HCC progression. A liver orthotopic transplantation model was used to evaluate the role of LDLR in HCC progression in vivo. RESULTS: Downregulation of LDLR was identified as a negative prognostic factor in human HCC. Reduced expression of LDLR in HCC cell lines impaired LDL uptake but promoted proliferation and metastasis in vitro and in vivo. Mechanistically, increasing intracellular de novo cholesterol biosynthesis was the chief contributor to malignant behaviors caused by LDLR inhibition, which could be rescued by simvastatin. Activation of the MEK/ERK pathway by LDLR downregulation partially contributed to intracellular cholesterol synthesis in HCC. CONCLUSIONS: Downregulation of LDLR may elevate intracellular cholesterol synthesis to accelerate proliferation and motility through a mechanism partially attributed to stimulation of the MEK/ERK signaling pathway. Repression of intracellular cholesterol synthesis with statins may constitute a targetable liability in the context of lower LDLR expression in HCC.

19.
Pharmacol Res ; 168: 105594, 2021 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-33826947

RESUMEN

Alcohol-associated liver disease (ALD) is a liver system disease caused by alcohol abuse, and it involves complex processes ranging from steatosis to fibrosis, cirrhosis and hepatocellular carcinoma. Steatosis and inflammation are the main phenomena involved in ALD. Ubiquitin-specific protease 22 (USP22) plays an important role in liver steatosis; however, its functional contribution to ALD remains unclear. USP22-silenced mice were fed a Lieber-DeCarli liquid diet. AML-12 and HEK293T cells were used to detect the interaction between USP22 and BRD4. Here, we report that hepatic USP22 expression was dramatically upregulated in mice with ALD. Inflammation and steatosis were significantly ameliorated following USP22 silencing in vivo, as indicated by decreased IL-6 and IL-1ß levels. We further showed that the overexpression of USP22 increased inflammation, while knocking down BRD4 suppressed the inflammatory response in AML-12 cells. Notably, USP22 functioned as a BRD4 deubiquitinase to facilitate BRD4 inflammatory functions. More importantly, the expression levels of USP22 and BRD4 in patients with ALD were significantly increased. In conclusion, USP22 acts a key pathogenic factor in ALD by deubiquitinating BRD4, which facilitates the inflammatory response and aggravates ALD.

20.
Int J Pharm ; 602: 120552, 2021 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-33798685

RESUMEN

Combined administration of drugs can improve efficacy and reduce toxicity; therefore, this combination approach has become a routine method in cancer therapy. The main combination regimens are sequential, mixed (also termed "cocktail"), and co-loaded; however, other combinations, such as administration of synergistic drugs and the use of formulations with different mechanisms of action, may exert better therapeutic effects. Tumor-associated macrophages (TAMs) play functional roles throughout tumor progression and exhibit characteristic phenotypic plasticity. Sialic acid (SA)-modified epirubicin liposomes (S-E-L) and SA-modified zoledronate liposomes (S-Z-L) administered separately kill TAMs, reverse their phenotype, and achieve antitumor effects. In this study, we examined the effects of a two-treatment combination for drug delivery, using sequential, mixed, and co-loaded drug delivery. We found that therapeutic effects differed between administration methods: mixed administration of S-E-L and S-Z-L, co-loaded administration of SA-modified liposomes (S-ZE-C), and sequential administration of S-E-L injected 24 h after S-Z-L did not inhibit tumor growth; however, sequential administration of S-Z-L injected 24 h after S-E-L resulted in no tumor growth, no toxicity to noncancerous tissue, and no death of mice, and exhibited 25% tumor shedding. Thus, our results thus encourage the further development of combined therapies for nanomedicines based on the mechanisms investigated here.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...