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1.
Autoimmunity ; 57(1): 2201412, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38425093

RESUMO

OBJECTIVE: To explore the effect of CD5-like molecule (CD5L) on rheumatoid arthritis (RA) fibroblast-like synoviocytes (RA-FLS) and the relative molecular mechanism of CD5L in it. METHODS: Recombinant protein CD5L was used to stimulate the cultured RA-FLS cells. The inflammation-related cytokines were determined by real time-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). The signal molecules and apoptosis-related molecules were detected by western blot assay (WB), and cell counting kit-8 (CCK-8) was used to detect the proliferation. RESULTS: CD5L can increase the production of IL-6, IL-8, and TNF-α and this effect can be inhibited by signal pathway inhibitor. At the same time, CD5L activated ERK1/2 MAPK signal, inhibitor treatment can weaken the intensity of phosphorylation. In addition, CD5L can enhance the proliferation ability of RA-FLS. CONCLUSION: CD5L induces the production of inflammatory cytokines in RA-FLS through the ERK1/2 MAPK pathway and increases cell survival.


Assuntos
Artrite Reumatoide , Membrana Sinovial , Humanos , Membrana Sinovial/metabolismo , Sistema de Sinalização das MAP Quinases , Artrite Reumatoide/metabolismo , Inflamação/metabolismo , Citocinas/metabolismo , Células Cultivadas , Fibroblastos/metabolismo , Proliferação de Células , Proteínas Reguladoras de Apoptose , Receptores Depuradores/metabolismo
2.
Nat Commun ; 15(1): 705, 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38267418

RESUMO

Toxic amyloid-beta (Aß) plaque and harmful inflammation are two leading symptoms of Alzheimer's disease (AD). However, precise AD therapy is unrealizable due to the lack of dual-targeting therapy function, poor BBB penetration, and low imaging sensitivity. Here, we design a near-infrared-II aggregation-induced emission (AIE) nanotheranostic for precise AD therapy. The anti-quenching emission at 1350 nm accurately monitors the in vivo BBB penetration and specifically binding of nanotheranostic with plaques. Triggered by reactive oxygen species (ROS), two encapsulated therapeutic-type AIE molecules are controllably released to activate a self-enhanced therapy program. One specifically inhibits the Aß fibrils formation, degrades Aß fibrils, and prevents the reaggregation via multi-competitive interactions that are verified by computational analysis, which further alleviates the inflammation. Another effectively scavenges ROS and inflammation to remodel the cerebral redox balance and enhances the therapy effect, together reversing the neurotoxicity and achieving effective behavioral and cognitive improvements in the female AD mice model.


Assuntos
Doença de Alzheimer , Feminino , Animais , Camundongos , Doença de Alzheimer/terapia , Espécies Reativas de Oxigênio , Peptídeos beta-Amiloides , Citoesqueleto , Inflamação , Placa Amiloide
3.
Front Plant Sci ; 14: 1164467, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37521920

RESUMO

Male sterility is a highly attractive agronomic trait as it effectively prevents self-fertilization and facilitates the production of high-quality hybrid seeds in plants. Timely release of mature pollen following anther dehiscence is essential for stamen development in flowering plants. Although several theories have been proposed regarding this, the specific mechanism of anther development in eggplant remains elusive. In this study, we selected an R2R3-MYB transcription factor gene, SmMYB108, that encodes a protein localized primarily in the nucleus by comparing the transcriptomics of different floral bud developmental stages of the eggplant fertile line, F142. Quantitative reverse transcription polymerase chain reaction revealed that SmMYB108 was preferentially expressed in flowers, and its expression increased significantly on the day of flowering. Overexpression of SmMYB108 in tobacco caused anther dehiscence. In addition, we found that SmMYB108 primarily functions as a transcriptional activator via C-terminal activation (amino acid 262-317). Yeast one-hybrid and dual-luciferase reporter assays revealed that genes (SmMYB21, SmARF6, and SmARF8) related to anther development targeted the SmMYB108 promoter. Overall, our results provide insights into the molecular mechanisms involved in the regulation of anther development by SmMYB108.

4.
Nat Commun ; 14(1): 4557, 2023 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-37507371

RESUMO

Glioblastoma (GBM) remains the most lethal malignant tumours. Gboxin, an oxidative phosphorylation inhibitor, specifically restrains GBM growth by inhibiting the activity of F0F1 ATPase complex V. However, its anti-GBM effect is seriously limited by poor blood circulation, the blood brain barrier (BBB) and non-specific GBM tissue/cell uptake, leading to insufficient Gboxin accumulation at GBM sites, which limits its further clinical application. Here we present a biomimetic nanomedicine (HM-NPs@G) by coating cancer cell-mitochondria hybrid membrane (HM) on the surface of Gboxin-loaded nanoparticles. An additional design element uses a reactive oxygen species responsive polymer to facilitate at-site Gboxin release. The HM camouflaging endows HM-NPs@G with unique features including good biocompatibility, improved pharmacokinetic profile, efficient BBB permeability and homotypic dual tumour cell and mitochondria targeting. The results suggest that HM-NPs@G achieve improved blood circulation (4.90 h versus 0.47 h of free Gboxin) and tumour accumulation (7.73% ID/g versus 1.06% ID/g shown by free Gboxin). Effective tumour inhibition in orthotopic U87MG GBM and patient derived X01 GBM stem cell xenografts in female mice with extended survival time and negligible side effects are also noted. We believe that the biomimetic Gboxin nanomedicine represents a promising treatment for brain tumours with clinical potential.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Nanopartículas , Humanos , Feminino , Animais , Camundongos , Glioblastoma/patologia , Nanomedicina , Linhagem Celular Tumoral , Membranas Mitocondriais/patologia , Barreira Hematoencefálica/metabolismo , Mitocôndrias , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/metabolismo
5.
Mol Nutr Food Res ; 67(11): e2200340, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36988616

RESUMO

SCOPE: Changes in composition of intestinal microbes may disrupt the balance of their interaction with a susceptible host, resulting in development of inflammatory bowel disease (IBD). METHODS AND RESULTS: The study applied in combination two Lactobacillus strains (L. rhamnosus BY-02, L. plantarum BY-05) ("LS treatment"), previously isolates from feces of healthy human infants, in a mouse model of dextran sodium sulfate (DSS)-induced colitis, and evaluates their ameliorative effect and its possible mechanism. LS treatment suppresses weight loss and colon shortening, and reduces disease activity index in the mice. It also has several additional beneficial effects: i) maintains goblet cell numbers and ameliorates intestinal barrier damage in colonic tissue; ii) alters intestinal microbial composition close to normal by increasing abundances of Muribaculaceae, Akkermansia, Clostridia, Oscillospiraceae, and Lachnospiraceae, and decreasing abundance of Escherichia-Shigella; iii) increases content of short-chain fatty acids; iv) reduces content of pro-inflammatory lipopolysaccharides; v) suppresses overactivation of TLR4/NF-κB inflammatory signaling pathway. CONCLUSION: Combination treatment with two Lactobacillus strains strongly ameliorates colitis symptoms in the mouse model by favorably altering intestinal microbial composition and suppressing inflammatory response.


Assuntos
Colite , Lacticaseibacillus rhamnosus , Lactobacillus plantarum , Humanos , Camundongos , Animais , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Intestinos , Colo/metabolismo , Lactobacillus , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Lactobacillus plantarum/metabolismo
6.
Eur J Med Res ; 28(1): 54, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36717930

RESUMO

OBJECTIVE: To observe the clinical features and efficacy of immunosuppressive therapy in patients with primary Sjögren's syndrome (PSS) combined with peripheral neuropathy (PN) syndrome and to explore the risk factors for PN in patients with PSS. METHODS: Sixty consecutive patients with PSS admitted to the Department of Rheumatology and Immunology, Wuhan No. 1 Hospital, from January 2014 to June 2020 were analysed retrospectively. Patients were divided into a PN group (N = 15) and a non-PN group (N = 45). The clinical characteristics of the two groups were compared, and the independent risk factors for PN combined with PSS were analysed by multivariate logistic regression. The patients with PSS combined with PN were followed up to observe the effect of immunosuppressive therapy. RESULTS: The patients with PN had a longer course of disease than those without PN (z = - 3.225, P = 0.001), and the incidence of Raynaud's phenomenon, anti-SSB antibody, rheumatoid factor and hyperglobulinaemia was higher (all P < 0.05) in patients with PN than in those without PN. Multivariate logistic regression analysis showed that hyperglobulinaemia, RF and anti-SSB antibodies were independent risk factors for PN with PSS (P < 0.05). Fourteen patients with PSS-PN were treated with immunosuppressants. The clinical symptoms of 10 patients were relieved, and mRS scores of 10 patients were decreased. CONCLUSION: PN is a common complication in PSS patients. Patients with PSS combined with PN have a longer course of disease and a significantly higher percentage of Raynaud's phenomenon, positive anti-SSB antibody, positive RF and hyperglobulinaemia. Immunosuppressive therapy was effective for partial remission of PN with PSS.


Assuntos
Doenças do Sistema Nervoso Periférico , Síndrome de Sjogren , Humanos , Síndrome de Sjogren/complicações , Síndrome de Sjogren/diagnóstico , Estudos Retrospectivos , Fatores de Risco , Imunossupressores/uso terapêutico , Doenças do Sistema Nervoso Periférico/etiologia , Doenças do Sistema Nervoso Periférico/complicações
7.
Clin Exp Immunol ; 212(3): 184-198, 2023 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-36427004

RESUMO

CD5L/AIM (apoptosis inhibitor of macrophage), as an important component in maintaining tissue homeostasis and inflammation, is mainly produced and secreted by macrophages but partially dissociated and released from blood AIM-IgM. AIM plays a regulatory role in intracellular physiological mechanisms, including lipid metabolism and apoptosis. AIM not only increases in autoimmune diseases, directly targets liver cells in liver cancer and promotes cell clearance in acute kidney injury, but also causes arteriosclerosis and cardiovascular events, and aggravates inflammatory reactions in lung diseases and sepsis. Obviously, AIM plays a pleiotropic role in the body. However, to date, studies have failed to decipher the mechanisms behind its different roles (beneficial or harmful) in inflammatory regulation. The inflammatory response is a "double-edged sword," and maintaining balance is critical for effective host defense while minimizing the adverse side effects of acute inflammation. Enhancing the understanding of AIM function could provide the theoretical basis for new therapies in these pathological settings. In this review, we discuss recent studies on the roles of AIM in lipid metabolism, autoimmune diseases and organic tissues, such as liver cancer, myocardial infarction, and kidney disease.


Assuntos
Neoplasias Hepáticas , Macrófagos , Humanos , Proteínas Reguladoras de Apoptose/metabolismo , Inflamação , Apoptose , Neoplasias Hepáticas/metabolismo
8.
Mikrochim Acta ; 189(11): 400, 2022 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-36190558

RESUMO

An antifouling sensing surface was constructed by crosslinking two-dimensional nanomaterial MXene with bovine serum albumin (BSA) denatured by urea previously. The immunoglobulin G (IgG) capture peptide was then modified to the surface to construct a highly selective antifouling electrochemical biosensor. Due to the large specific surface area and good electrical conductivity of MXene, the sensitivity of the biosensor is significantly enhanced. The biosensor at a working potential of around - 0.18 V (vs. Ag/AgCl) provides a wide linear detection range (0.1 ng/mL to 10 µg/mL) for IgG with a limit of detection of 23 pg/mL (3σ/k). The result is consistent with that obtained from the commercial enzyme-linked immunosorbent kit. Compared with BSA, which is usually used as a passivator or blocker for biosensing platforms, the hydrogel formed through the peptide chain obtained from BSA with good hydrophilicity can provide a better antifouling sensing surface to resist nonspecific adsorption. The prepared biosensor can quantitatively detect the concentration of IgG in complex human serum with high sensitivity. Thus, the antifouling sensing surface constructed without expensive antifouling materials and complex process is expected to develop as a variety of electrochemical biosensors and used for the clinical testing of biomarkers. Graphical abstract An antifouling sensing surface was constructed by crosslinking two-dimensional nanomaterial MXene with bovine serum albumin (BSA) denatured by urea previously. The immunoglobulin G (IgG) capture peptide was then modified to the surface to construct a highly selective antifouling electrochemical biosensor.


Assuntos
Técnicas Biossensoriais , Imunoglobulina G , Técnicas Biossensoriais/métodos , Humanos , Hidrogéis , Imunoglobulina G/análise , Imunoadsorventes , Peptídeos , Soroalbumina Bovina , Ureia
9.
Pharm Dev Technol ; 27(7): 759-765, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36004557

RESUMO

The structural instability of inactivated Foot-and-mouth disease virus antigen hinders the development of vaccine industry. The use of an inexpensive, biocompatible formulation to slow down the degradation of antigen would address the problem. Here, phosphate-buffered saline (PBS) was showed to be effective in stabilizing 146S and hence determined as basic solution buffer. Excipients such as trehalose, sucrose, arginine, cysteine, calcium chloride, BSA and ascorbic acid were found to protect 146S from massive structural breakdown. Using orthogonal test, we confirmed the novel formulation as a combination of 5% (w/v) trehalose, 5% (w/v) sucrose, 0.05 M arginine, 0.01 M cysteine, 0.01 M calcium chloride, 1% (W/V) BSA and 0.001 M ascorbic acid in PBS. The formulation increased vaccine stabilization, with retention rate of 14% after storage at 4 °C for 14 months. Particle size for vaccine was at approximately 220 nm and physicochemical detecting findings were rarely abnormal in morphology and emulsion type. In summary, these results revealed that the novel formulation is beneficial to make the FMD vaccine more stable and effective, reducing the dependence on cold storage and delivery.


Assuntos
Vírus da Febre Aftosa , Febre Aftosa , Vacinas Virais , Animais , Arginina , Ácido Ascórbico , Cloreto de Cálcio , Cisteína , Emulsões , Excipientes , Febre Aftosa/prevenção & controle , Vírus da Febre Aftosa/química , Fosfatos , Sacarose , Trealose , Vacinas Virais/química
10.
Chem Sci ; 13(26): 7947-7954, 2022 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-35865906

RESUMO

The transformations that allow the direct removal of hydrogen from their corresponding saturated counterparts by the dehydrogenative strategy are a dream reaction that has remained largely underexplored. In this report, a straightforward and robust cobaloxime-catalyzed photochemical dehydrogenation strategy via intramolecular HAT is described for the first time. The reaction proceeds through an intramolecular radical translocation followed by the cobalt assisted dehydrogenation without needing any other external photosensitizers, noble-metals or oxidants. With this approach, a series of valuable unsaturated compounds such as α,ß-unsaturated amides, enamides and allylic and homoallylic sulfonamides were obtained in moderate to excellent yields with good chemo- and regioselectivities, and the synthetic versatility was demonstrated by a range of transformations. And mechanistic studies of the method are discussed.

11.
World J Clin Cases ; 10(10): 3014-3026, 2022 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-35647133

RESUMO

BACKGROUND: Dry eye syndrome (DES) is a common disease with various clinical manifestations. DES had a significant association with diabetes. Blink reflex (BR) is also known as trigeminal nerve facial reflex. The stimulation of corneal nerves is one of the origins of BR stimulation. The parasympathetic fibers sent out through the facial nerve are the outlet of tear reflexes. BR can be used to assess the function of the corneal nerve closed-loop; however, whether the BR changes in these patients is unclear. AIM: To understand the morphology and function of the corneal nerve in patients with dry eyes having diabetes or not. METHODS: This study enrolled 131 patients who visited the inpatient and outpatient services of ophthalmology and endocrinology departments between January 2019 to August 2020 with subjective symptoms of dry eyes and non-dry eye reasons, as well as volunteers such as colleagues. The patients were divided into four groups: DEwDM, with dry eyes having type 2 diabetes mellitus (T2DM); DMnDE, with T2DM not having dry eyes; DEnDM, with dry eyes not having diabetes; and nDMnDE, with neither dry eyes nor diabetes. The tear film break-up time, Schirmer I test, in vivo confocal microscopy, and BR were performed. RESULTS: The DEwDM, DMnDE, DEnDM, and nDMnDE groups included 56, 22, 33, and 20 patients, respectively. Sex and age were not statistically different among the four groups. The nerve fiber length (NFL) of patients in the DEwDM, DEnDM, and DMnDE groups reduced (P < 0.001, P = 0.014, and P = 0.001, respectively). No significant difference in corneal nerve fiber density (NFD) (P = 0.083) and corneal nerve branch density (NBD) (P = 0.195) was found among the four groups. The R1 Latency of blink reflexes increased only in the DEwDM group (P = 0.008, P = 0.001, P < 0.001, compared with the DMnDE, DEnDM, and nDMnDE groups, respectively). The NBD and R1 Latency were different between DEwDM and DEnDM groups in patients with moderate and severe dry eyes. CONCLUSION: The corneal nerve morphology changed in patients with dry eyes or diabetes, or with both, while the function of corneal nerve closed-loop reduced only in those with dry eyes and diabetes.

12.
Biosens Bioelectron ; 208: 114216, 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35349895

RESUMO

A novel ratio electrochemical biosensor based on multi-functional nanocomposite was developed. Fe3O4 was synthesized in situ on carboxyl functionalized 2D nanomaterial MXene, and then covalently bonded with [Ru(NH3)6]3+ to obtain nanocomposites MXC-Fe3O4-Ru. Fe3O4 and [Ru(NH3)6]3+ can neutralize the electronegativity of the MXene to make the nanocomposites electrically neutral. Combine with the good hydrophilicity and conductivity of MXene, the nanocomposites can be utilized to construct antifouling electrochemical biosensors without modifying with specific antifouling materials. Moreover, Fe3O4 can endow the nanocomposites with magnetism, and [Ru(NH3)6]3+ is used as an internal standard molecule. The strong magnetic MXC-Fe3O4-Ru can be easily separated and firmly modified on the magnetic gold electrode (MGE). DNA double-stranded (dsDNA) containing an ferrocene (Fc)-modified carcinoembryonic antigen (CEA) aptamer can be specifically captured to the surface of the electrode by amido bond. In the presence of CEA, CEA binds to the aptamer and leaves the electrode surface, the electrochemical signal of Fc decreases, while the electrochemical signal of [Ru(NH3)6]3+ is fixed on the electrode surface remains basically unchanged. The ratio of the electrochemical signals of Fc and [Ru(NH3)6]3+ is proportional to the CEA concentration. The linear range of the sensor is 1 pg/mL to 1 µg/mL with a detection limit of 0.62 pg/mL. With the excellent antifouling performance, good conductivity of the nanocomposite, and the application of the ratiometric strategy, the biosensor can achieve high selectivity, accuracy, and sensitivity for the detection of targets even in complex samples, such as FBS and clinical serum.


Assuntos
Incrustação Biológica , Técnicas Biossensoriais , Nanocompostos , Incrustação Biológica/prevenção & controle , Antígeno Carcinoembrionário , Técnicas Eletroquímicas , Ouro/química , Limite de Detecção , Fenômenos Magnéticos , Nanocompostos/química
13.
Clin Exp Rheumatol ; 40(9): 1779-1788, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35200127

RESUMO

OBJECTIVES: To explore the role of interleukin 34 (IL-34) in rheumatoid arthritis (RA) and its related signalling pathways as well as the expression levels of IL-34 in collagen-induced arthritis (CIA) modelling mice. METHODS: Recombination IL-34 was used to stimulate cultured RA fibroblast-like synoviocytes (RA-FLS). The expression levels of inflammatory cytokines were determined by enzyme-linked immunosorbent assay (ELISA), and the levels of phosphorylation signalling molecules were detected by western blotting assay (WB). After the establishment of the CIA model, paw indexes and serum IL-34 expression levels of mice were evaluated. RESULTS: IL-34 significantly increased the secretion of IL-8 and TNF-α but had no significant effect on IL-6, and this effect could be impaired by signal inhibitors. At the same time, IL-34 activated multiple signalling pathways, whereas treating with inhibitors could reduce phosphorylation intensity. In animal experiments, mice in the model group had lost weight, and their paws were obviously swollen, ulcerous, and even stiffened. The hyperplasia of synovial tissue, infiltration of many inflammatory cells, and destruction of bone and cartilage from the typical pannus formation were also apparently observed. CONCLUSIONS: IL-34 can mediate the production and secretion of IL-8 and TNF-α in RA-FLS cells through MAPKs, PI3K/Akt, JAK and NF-κB signalling pathways, while the expression of serum IL-34 in collagen-induced arthritis mice is also upregulated.


Assuntos
Artrite Experimental , Artrite Reumatoide , Interleucinas , Animais , Artrite Experimental/induzido quimicamente , Artrite Experimental/genética , Artrite Experimental/metabolismo , Artrite Reumatoide/genética , Artrite Reumatoide/metabolismo , Células Cultivadas , Citocinas/metabolismo , Fibroblastos/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Interleucinas/genética , Interleucinas/metabolismo , Camundongos , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositol 3-Quinases/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Membrana Sinovial/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
14.
J Phys Chem A ; 125(47): 10155-10164, 2021 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-34793164

RESUMO

To provide guiding information for developing efficient and stable catalysts for epoxide hydration, we investigated the mechanism of propylene oxide (PO) to 1,2-propylene glycol (PG) using density functional theory (DFT) calculations. The mechanism was identified to follow the cooperative bimetallic mechanism in which a metal-salen complex activated H2O attacks the middle carbon atom of a metal-salen complex activated PO from the oxygen side of three-membered ring. Analyses reveal that the distortion energy correlates linearly with the barrier, and the hydrogen bonding between H2O and PO increases from reaction precursors to transition states. A nice linear relationship exists between the ratio of square root of ionic potential to the square of the distance from the metal ion spherical surface to the oxygen atom center of PO. It is demonstrated that the substrates with larger polarizability tend to have lower hydration barriers and the influence of ligands is less than that of metal centers and substrates. Modifying metal ions is the first choice for developing metal-salen catalysts, and metal ions with more formal charges and larger radius are expected to exhibit high activity. These findings shed lights on the mechanism and provide guiding information for developing efficient metal-salen catalysts for epoxide hydration.

15.
Medicine (Baltimore) ; 100(39): e27219, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34596119

RESUMO

ABSTRACT: Cluster of differentiation 5 antigen-like (CD5L), derived from alveolar epithelial cells partly, is a secreted protein. It is shown that CD5L is associated with lung inflammation and systemic inflammatory diseases, but the relationship between CD5L and trauma-related acute lung parenchymal injury (PLI), acute lung injury or acute respiratory distress syndrome (ARDS) is unclear. This study aims to explore the value of serum CD5L levels in predicting trauma-associated PLI/ARDS and its potential clinical significance.This is a prospective observational study, and a total of 127 trauma patients were recruited from the emergency department (ED), and among them, 81 suffered from PLI/ARDS within 24 hours after trauma, and 46 suffered from trauma without PLI/ARDS. Fifty healthy subjects from the medical examination center were also recruited as controls for comparison. The serum CD5L level was measured within 24 hours of admission. The receiver operating characteristic analysis and logistic regression analysis were used to identify the correlation between high CD5L and trauma associated-PLI/ARDS within 24 hours following trauma.The trauma associated-PLI/ARDS subjects showed a significantly higher level of serum CD5L on emergency department admission within 24 hours after trauma compared with its level in non-trauma associated-PLI/ARDS subjects and healthy subjects. The initial CD5L concentration higher than 150.3 ng/mL was identified as indicating a high risk of PLI/ARDS within 24 hours following trauma (95% confidence interval: 0.674-0.878; P < .001). Moreover, CD5L was an independent risk factor for trauma associated-PLI/ARDS within 24 hours following trauma.CD5L could predict PLI/ARDS within 24 hours following trauma.


Assuntos
Lesão Pulmonar Aguda/sangue , Proteínas Reguladoras de Apoptose/sangue , Receptores Depuradores/sangue , Síndrome do Desconforto Respiratório/sangue , Ferimentos e Lesões/sangue , Lesão Pulmonar Aguda/etiologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Síndrome do Desconforto Respiratório/etiologia , Ferimentos e Lesões/complicações
16.
Phys Chem Chem Phys ; 22(39): 22417-22425, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32996507

RESUMO

CoIII(salen)-X (X = Cl-, OAc-, and OTs-) mediated hydration of propylene oxide (PO) to propylene glycol has been investigated in detail using density functional theory (DFT) calculations. Two kinds of reaction mechanisms, the concerted and stepwise pathways, were scrutinized. For the eight concerted routes, the cooperative bimetallic route in which the middle carbon atom is attacked by the nucleophilic oxygen atom (route VI-m) was calculated to be the most favorable, and among the three catalysts examined H2O-CoIII-OTs was found to be the most active, due to the strong hydrogen bonding between the nucleophilic H2O and the ring oxygen atom in the epoxides as well as the extra π-π stacking interaction. For the stepwise mechanism which consists of the formation of H2O-CoIII-OH, the ring-opening of PO and propylene glycol formation, our studies reveal that different H2O-CoIII-Xs behave kinetically very similarly in the course of propylene glycol formation, but show a notable difference in the rate of H2O-CoIII-OH formation with Cl- > OAc- > OTs-. The rate ordering with which we rationalize the experimental phenomena well is disclosed to be consistent with the nucleophilicity of the counterions by molecular electrostatic potential, condensed Fukui function and condensed local softness. We show that the nucleophilicity of the counterion determines the favorable mechanism that PO hydration follows.

17.
Stroke ; 51(8): 2568-2572, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32684142

RESUMO

BACKGROUND AND PURPOSE: The retina, as an externally located neural tissue, offers unique advantages in investigating the effect of therapeutic intervention on the brain. In this study, we put forth a clinically relevant model of retinal ischemia and reperfusion in nonhuman primates. METHODS: Acute retinal artery ischemia and reperfusion was induced by injecting an autologous clot into the ophthalmic artery of adult rhesus monkeys, and recanalization was achieved by focal thrombolysis with tPA (tissue-type plasminogen activator). Digital subtraction angiography and fluorescein angiography were used to evaluate blood flow in the retina and the choroid. Electroretinogram, optical coherence tomography, and hematoxylin and eosin staining were used to evaluate the structure and function of the retina after ischemia. RESULTS: Digital subtraction angiography and fluorescein angiography images confirmed occlusion of the ophthalmic and central retinal arteries, as well as recanalization after tPA thrombolysis. Electroretinogram indicated retinal functional damage following ischemia, and thrombolysis partially rescued its impairment. Optical coherence tomography and hematoxylin and eosin staining revealed ischemia-induced changes in the retina, and tPA partially mitigated these damages. CONCLUSIONS: This novel acute retinal artery ischemia and reperfusion model in rhesus monkeys may closely simulate retinal ischemia/reperfusion in clinical practice and provide an optimal platform for screening neuroprotective strategies.


Assuntos
Modelos Animais de Doenças , Oclusão da Artéria Retiniana/diagnóstico por imagem , Oclusão da Artéria Retiniana/cirurgia , Artéria Retiniana/diagnóstico por imagem , Artéria Retiniana/cirurgia , Angiografia Digital/métodos , Animais , Macaca mulatta , Masculino , Primatas , Reperfusão
18.
Front Pharmacol ; 11: 44, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32116719

RESUMO

BACKGROUD: Contrast-induced acute kidney injury (CI-AKI) is the most common adverse reaction caused by contrast media, which has been reported to prolong hospitalization and increase mortality and morbidity. The hypertensive population has proved susceptible to CI-AKI. Unfortunately, no therapeutic has been shown to prevent and cure CI-AKI effectively. A few studies have shown the protection of amlodipine on renal function, but the relationship between amlodipine and CI-AKI in hypertensive group is unknown, we aimed to study the effects of amlodipine on CI-AKI and overall survival in a large Chinese hypertensive cohort. METHODS: A retrospective, matched, cohort study was conducted among adults hospitalized at the Third Xiangya Hospital of Central South University from October 2007 to May 2017. CI-AKI was the primary end point of the trial, time-related all-cause mortality (including in-hospital) and length of hospital stay were the secondary end points. Propensity Score Matching was used to reduce the effect of selection bias and potential confounding. RESULTS: 868 patients with and 1,798 ones without amlodipine before contrast administration were included. The incidence of CI-AKI was 10.50%. The unadjusted, adjusted, and propensity-score matched incidence of CI-AKI were lower in patients treated with amlodipine (OR, 0.650; P = 0 .003; OR, 0.577; P = 0.007; OR, 0.687; P = 0.015, respectively), and the same results were found in the subgroups of diabetes, chronic kidney disease (CKD), non-CKD, low-osmolar, and elderly. Moreover, amlodipine reduced hospital stay, whether matched or not (7.08 ± 7.28 vs 7.77 ± 7.82, P = 0.027, before matching; vs 7.81 ± 7.58, P = 0.040, after matching). 1,046 patients finished follow-up including 343 amlodipine users and 703 non-users. The overall mortality was significantly lower among amlodipine users (10.79%) than controls (16.07%), the significant difference was found in survival between them (P = 0.024, log-rank test), amlodipine was associated with longer overall survival [HR, 0.623; 95% CI (0.430-0.908), P = 0.014]. CONCLUSION: In conclusion, we first found amlodipine treatment before contrast exposure played a role in protecting hypertensive patients from CI-AKI and prolonging survival.

19.
Chem Sci ; 10(12): 3535-3542, 2019 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-30996945

RESUMO

Three red cyclometalated iridium(iii) complexes (4tfmpq)2Ir(dipdtc), (4tfmpq)2Ir(dpdtc) and (4tfmpq)2Ir(Czdtc) (4tfmpq = 4-(4-(trifluoromethyl)phenyl)quinazoline, dipdtc = N,N-diisopropyl dithiocarbamate, dpdtc = N,N-diphenyl dithiocarbamate, and Czdtc = N-carbazolyl dithiocarbamate) containing the unique four-membered Ir-S-C-S backbone ring were synthesized in five minutes at room temperature with good yields, and the Gibbs free energy calculation results indicate that all reactions are exothermic and thermodynamically favorable processes. The emission colors (λ peak = 641-611 nm), photoluminescence quantum efficiencies (Φ P = 58.3-93.0%) and bipolar properties can be effectively regulated by introducing different electron-donating substituents into the dithiocarbamate ancillary ligands. Employing these emitters, organic light emitting diodes (OLEDs) with double emissive layers exhibit excellent performances with a maximum brightness over 60 000 cd m-2, a maximum current efficiency of 40.68 cd A-1, a maximum external quantum efficiency (EQEmax) of 30.54%, and an EQE of 26.79% at the practical luminance of 1000 cd m-2. These results demonstrate that Ir(iii) complexes with sulfur-containing ligands can be rapidly synthesized at room temperature, which is key to the production of metal luminescent materials for large-scale application in highly efficient OLEDs.

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