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1.
JCI Insight ; 4(21)2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31672934

RESUMO

Neutrophils play critical roles during the initial phase of hepatic ischemia/reperfusion injury (HIRI). However, the regulation of neutrophil activation, infiltration, and proinflammatory cytokine secretion has not been fully elucidated. In this study, we revealed that OX40 was expressed by neutrophils, its expression in neutrophils was time-dependently upregulated following HIRI, and Ox40 knockout markedly alleviated liver injury. Compared with wild-type neutrophils, the adoptive transfer of Ox40-/- neutrophils decreased HIRI in neutrophil-depleted Rag2/Il2rg-/- or Ox40-/- mice. Moreover, consistently, the in vitro experiments showed that Ox40 not only prolonged neutrophil survival but also promoted proinflammatory cytokines, ROS production, and even neutrophil chemotaxis. Further investigation demonstrated that the knockout of Ox40 in neutrophils inhibited NF-κB signaling via the TRAF1/2/4 and IKKα/IKKß/IκBα pathways. OX40L and OX86 stimulation could enhance neutrophil activation and survival in vitro and in vivo. In conclusion, our study provides a new understanding of OX40, which is expressed not only in adaptive immune cells but also in innate immune cells, i.e., neutrophils, contributing to the activation and survival of neutrophils. These findings provide a novel potential therapeutic target for the prevention of HIRI during liver transplantation or hepatic surgery.

2.
J Asian Nat Prod Res ; : 1-10, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31773971

RESUMO

Gramine can be intelligently and efficiently supplied with N, N-dimethylamino group and then reacted with the corresponding sulfonyl chlorides to synthesize N, N-dimethylarylsulfonamides. We herein designed and controlled synthesis of N, N-dimethylarylsulfonamide derivatives, and first reported the results of the nematicidal activity of 15 title compounds 3a-o against Meloidogyne incongnita in vitro, respectively. Among all of the title derivatives, compounds 3a, 3c, 3k, and 3o exhibited potent nematicidal activity with median lethal concentration (LC50) values ranging from 0.22 to 0.26 mg/L. Most noteworthy, N, N-dimethyl-4-methoxyphenylsulfonamide (3c) and N, N-dimethyl-8-quinolinesulfonamide (3o) showed the best promising and pronounced nematicidal activity, with LC50 values of 0.2381 and 0.2259 mg/L, respectively.

3.
Biomed Pharmacother ; 119: 109400, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31514067

RESUMO

AIMS: Post-operative cognitive dysfunction (POCD) occurs after major surgery in elderly patients and affects the quality of patients' lives. The present study aims to explore the protective effects and possible mechanisms of compound K in old mice with POCD caused by partial hepatectomy. METHODS: Sixteen month-old mice were administered different doses of compound K from the 8th day to 14th day after partial hepatectomy. Cognitive function was subsequently measured with a Morris water-maze (MWM) test. Serum inflammatory cytokine levels were measured by magnetic bead panel; levels of cytokines in the hippocampus were analyzed using immunohistochemistry and immunoblotting. The mRNA levels of target genes were measured using real-time PCR. RESULTS: Compared with the model group, MWM scores were significantly attenuated at days 10 and 14 post-surgery in mice receiving compound K (10, 30 mg/kg) in a dose-dependent manner. Both systemic and local cytokine levels were reduced after treatment of compound K. The alterations in serum lipids were independent of the attenuation of POCD syndrome. An inhibitor of liver X receptor-α (LXRα), GGPP, reversed the effects of compound K. CONCLUSIONS: The results provide evidence for an alleviation of POCD by compound K via local inflammation inhibition in hippocampus tissue; furthermore, the data suggests the mechanism involves the LXRα pathway. The present study supports further evaluation of compound K as a potential effective modulator for POCD.

4.
Opt Express ; 27(17): 23981-23995, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31510294

RESUMO

The blue laser beam-excited surface-enhanced Raman scattering (SERS)-based pH sensing holds great promise for avoiding undesired thermal heating effect on some special temperature-vulnerable molecules, as compared to the vast majority studies by exciting in the red or near-infrared (NIR). Herein, we report an ingenious approach to support core-shell Au@Ag nanodendrites (NDs) on TiO2 nanowires, which can possess enhanced SERS activity under 473 nm laser excitation, owing to the improved charge-transfer effect on modified TiO2 support by inserting plasmonic Au@Ag. By using pH-indicating 4-mercaptobenzoic acid (4-MBA), the obtained TiO2/Au@Ag NDs can not only exhibit high sensitive linear-responses of pH changes ranging from pH 4.0 to 9.0 in different solutions (deionized water, NaCl, CaCl2, and MgCl2) but also provide excellent temperature stability under 4°C, 25°C and 37°C temperatures as well as good time stability after storage for 10 days. The established SERS-pH sensing by using shorter wavelength laser excitation is highly desirable for understanding physiological process in temperature-vulnerable microenvironment.

5.
Nat Commun ; 10(1): 4246, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31534137

RESUMO

Allergic asthma is an inflammatory disorder of the airway without satisfactory traditional therapies capable of controlling the underlying pathology. New approaches that can overcome the detrimental effects of immune dysregulation are thus desirable. Here we adoptively transfer ovalbumin (OVA) peptide-primed CD4-CD8- double negative T (DNT) cells intravenously into a mouse model of OVA-induced allergic asthma to find that OVA-induced airway hyperresponsiveness, lung inflammation, mucus production and OVA-specific IgG/IgE production are significantly suppressed. The immunosuppressive function of the OVA-specific DNT cells is dependent on the inhibition of CD11b+ dendritic cell function, T follicular helper cell proliferation, and IL-21 production. Mechanistically, Lag3 contributes to MHC-II antigen recognition and trogocytosis, thereby modulating the antigen-specific immune regulation by DNT cells. The effectiveness of ex vivo-generated allergen-specific DNT cells in alleviating airway inflammation thus supports the potential utilization of DNT cell-based therapy for the treatment of allergic asthma.

6.
Mol Med Rep ; 20(4): 3085-3094, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31432123

RESUMO

The present study was aimed to observe the protective effect of rapamycin on cognitive dysfunction induced by sevoflurane in aged rats and its effect on autophagy­related proteins, and to investigate the regulatory mechanism of the Toll­like receptor 4/myeloid differentiation primary response 88/nuclear factor­κB (TLR4/MyD88/NF­κB) signaling pathway. Fifty Sprague­Dawley rats were randomly assigned to a control group, a sevoflurane group, a rapamycin pretreatment group, a TLR4 inhibitor group and a 3MA autophagy inhibitor group. A water maze test was used to evaluate the cognition and memory of rats. Hematoxylin and eosin (H&E) staining was performed to observe pathological changes of brain tissue. A TUNEL assay was used to detect the apoptosis of brain tissue. ELISA was used to assess changes in brain injury markers and inflammatory factors. A western blot assay or quantitative reverse transcription PCR (RT­qPCR) were performed to determine the expression of autophagy­related proteins and the TLR4/MyD88/NF­κB signaling pathway in brain tissue. The results revealed that rapamycin could improve cognitive dysfunction of aged rats induced by sevoflurane. Rapamycin was identified to play a therapeutic role, including mitigating brain tissue damage, inhibiting apoptosis, and activating autophagy in a sevoflurane­treated aged rat model. This function of rapamycin was demonstrated to depend on the TLR4/MyD88/NF­κB signaling pathway.

8.
Int J Biol Macromol ; 136: 1060-1068, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31202848

RESUMO

Gluconic acid (GA) and its alkali salts are extensively used in the food, feed, beverage, textile, pharmaceutical and construction industries. However, the cost-effective and eco-friendly production of GA remains a challenge. The biocatalytic process involving the conversion of glucose to GA is catalysed by glucose oxidase (GOD), in which the catalytic efficiency is highly dependent on the GOD stability. In this study, we used in silico design to enhance the stability of glucose oxidase from Aspergillus niger. A combination of the best mutations increased the apparent melting temperature by 8.5 °C and significantly enhanced thermostability and thermoactivation. The variant also showed an increased optimal temperature without compromising the catalytic activity at lower temperatures. Moreover, the combined variant showed higher tolerance at pH 6.0 and 7.0, at which the wild-type enzyme rapidly deactivated. For GA production, an approximate 2-fold higher GA production yield was obtained, in which an almost complete conversion of 324 g/L d-glucose to GA was achieved within 18 h. Collectively, this work provides novel and efficient approaches for improving GOD thermostability, and the obtained variant constructed by the computational strategy can be used as an efficient biocatalyst for GA production at industrially viable conditions.

9.
J Asian Nat Prod Res ; : 1-11, 2019 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-31120307

RESUMO

A series of sulfonate derivatives of sesamol were synthesized and evaluated for their insecticidal activity against a crop-threatening agricultural pest, the pre-third-instar larvae of Mythimna separata in vivo. Among all the target compounds, compounds 3b, 3g, 3h, and 3p exhibited more promising insecticidal activity than sesamol and toosendanin, and the final mortality rates (FMRs) of 3b, 3g, 3h, 3p, 1, and toosendanin were 60.7%/60.7%/67.9%/53.6%/32.1%/50.0%, respectively. Especially compound 3h exhibited the most potent insecticidal activity with FMRs of 67.9%. This suggested that a 4-fluorophenylsulfonyl group introduced at the hydroxyl position of sesamol was necessary for obtaining the most potent compound.

10.
J Asian Nat Prod Res ; : 1-10, 2019 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-31046458

RESUMO

Sixteen sulfonate derivatives of maltol were synthesized and screened in vitro for their anti-oomycete and nematicidal activity against Phytophthora capsici and Bursaphelenchus xylophilus, respectively. Among all the compounds, 3e, 3m, and 3p exhibited the most promising and pronounced anti-oomycete activity against P. capsici than zoxamide, and the EC50 values of 25.42, 18.44, 23.69, and 27.99 mg/L, respectively; compounds 3e, 3m, 3n, and 3p exhibited potent nematicidal activity with LC50 values ranging from 1 to 2 mg/L, especially 3m and 3n showed the best promising and pronounced nematicidal activity, with LC50 values of 1.1762 and 1.2384 mg/L, respectively.

11.
Int J Cardiovasc Imaging ; 35(8): 1499-1508, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31037475

RESUMO

Resting two-dimensional speckle tracking echocardiography (2D-STE) identified right ventricular (RV) systolic function were reported to predict exercise capacity in pulmonary hypertension (PH) patients, but little attention had been payed to 2D-STE detected RV diastolic function. Therefore, we aim to elucidate and compare the relations between 2D-STE identified RV diastolic/systolic functions and peak oxygen consumption (PVO2) determined by cardiopulmonary exercise testing (CPET) in pre-capillary PH. 2D-STE was performed in 66 pre-capillary PH patients and 28 healthy controls. Linear correlation and multivariate regression analyses were performed to evaluate and compare the relations between RV 2D-STE parameters and PVO2. Receiver operating characteristic curves were used to compare the predictive value of 2D-STE parameters in predicting the cut-off-PVO2 < 11 ml/min/kg. There were significant differences of all the 2D-STE parameters between PH patients and healthy controls. In patients, RV-peak global longitudinal strain (GLS, rs = - 0.498, P < 0.001), RV- peak systolic strain rate (GSRs, rs = - 0.537, P < 0.001) and RV- peak early diastolic strain rate (GSRe, rs = 0.527, P < 0.001) significantly correlated with PVO2, but no significant correlation was observed between RV- peak late diastolic strain rate (GSRa, rs = 0.208, P = 0.093) and PVO2. The first multivariate regression analysis of clinical data without echocardiographic parameters identified WHO functional class, NT-proBNP and BMI as independent predictors of PVO2 (Model-1, adjusted r2 = 0.421, P < 0.001); Then we added conventional echocardiographic parameters and 2D-STE parameters to the clinical data, identified S,(Model-2,adjusted r2 = 0.502, P < 0.001), RV-GLS (Model-3, adjusted r2 = 0.491, P < 0.001), RV-GSRe (Model-4, adjusted r2 = 0.500, P < 0.001) and RV-GSRs (Model-5, adjusted r2 = 0.519, P < 0.001) as independent predictors of PVO2, respectively. The predictive power was increased, and Model-5 including RV-GSRs showed the highest predictive capability. ROC curves found RV-GSRs expressed the strongest predictive value (AUC = 0.88, P < 0.001), and RV-GSRs > - 0.65/s had a 88.2% sensibility and 82.2% specificity to predict PVO2 < 11 ml/min/kg. 2D-STE assessed RV function improves the prediction of exercise capacity represented by PVO2 in pre-capillary PH.


Assuntos
Ecocardiografia Doppler/métodos , Tolerância ao Exercício , Hipertensão Pulmonar/diagnóstico por imagem , Função Ventricular Direita , Adulto , Estudos de Casos e Controles , Estudos Transversais , Teste de Esforço , Feminino , Humanos , Hipertensão Pulmonar/fisiopatologia , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Adulto Jovem
12.
FASEB J ; 33(7): 8490-8503, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30951375

RESUMO

The liver is a central immunologic organ with a high density of myeloid and lymphoid immune cells that play important roles in the development and progression of nonalcoholic steatohepatitis (NASH). However, the immune-cell-mediated regulation of NASH and its underlying mechanisms remain obscure. In this study, Prf1null mice showed significantly higher plasma alanine transaminase levels, with increased liver fat accumulation, lobular inflammation, and focal necrosis compared with wild-type (WT) mice after 4 wk of feeding on a methionine- and choline-deficient diet (MCD) or 16 wk of feeding on a high-fat diet. Perforin deficiency promoted the M1 polarization of infiltrated monocytes. Moreover, MCD-fed Prf1null mice exhibited increased accumulation, survival, activation, and proinflammatory cytokine production of CD8 T cells but not NK cells or CD4 T cells. Adoptive transfer of CD8 T cells or NK cells from WT or Prf1null mice, together with non-CD8 cells or non-NK cells from WT mice, indicated that CD8 T-cell-derived perforin participates in the mechanism regulating liver inflammation and thus plays a protective role in the development of NASH. Perforin-deficient CD8 T cells exhibited decreased cytotoxicity toward bone marrow-derived M1 monocytes and macrophages. According to the RNA sequencing data, the perforin deficiency inhibited cell apoptosis and enhanced the activation, migration, and proinflammatory cytokine production of CD8 T cells in mice with NASH. Furthermore, we found higher plasma soluble perforin levels and hepatic perforin expression in NASH patients, suggesting clinical relevance of the findings. We have elucidated an important role for the cytotoxic immune effector molecule perforin from CD8 T cells in restricting hepatic inflammation in mice with NASH and suggest that therapies designed to maximize the function of endogenous perforin in CD8 T cells might have potential benefits as NASH treatments.-Wang, T., Sun, G., Wang, Y., Li, S., Zhao, X., Zhang, C., Jin, H., Tian, D., Liu, K., Shi, W., Tian, Y., Zhang, D. The immunoregulatory effects of CD8 T-cell-derived perforin on diet-induced nonalcoholic steatohepatitis.

13.
J Nucl Cardiol ; 2019 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-30993654

RESUMO

BACKGROUND: This study aimed to compare the accuracy of gated-SPECT (GSPECT) and gated-PET (GPET) in the assessment of left ventricular (LV) end-diastolic volumes (EDVs), end-systolic volumes (ESVs) and LV ejection fractions (LVEFs) among patients with prior myocardial infarction (MI). METHODS: One hundred and sixty-eight consecutive patients with MI who underwent GSPECT and GPET were included. Of them, 76 patients underwent CMR in addition to the two imaging modalities. The measurements of LV volumes and LVEF were performed using Quantitative Gated SPECT (QGS), Emory Cardiac Toolbox (ECTB), and 4D-MSPECT (4DM). RESULTS: The correlation between GPET, GSPECT, and CMR were excellent for LV EDV (r = 0.855 to 0.914), ESV (r = 0.852 to 0.949), and LVEF (r = 0.618 to 0.820), as calculated from QGS, ECTB, and 4DM. In addition, subgroup analysis revealed that EDV, ESV, and LVEF measured by GPET were accurate in patients with different extents of total perfusion defect (TPD), viable myocardium, and perfusion/metabolic mismatch. Furthermore, multivariate regression analysis identified that mismatch score was associated with the difference in EDV (P < 0.05) measurements between GPET and CMR. CONCLUSIONS: In patients with MI, LV volumes and LVEF scores measured by both GSPECT and GPET imaging were comparable to those determined by CMR, but should not be interchangeable in individual patients.

14.
Zhonghua Wei Chang Wai Ke Za Zhi ; 22(3): 267-272, 2019 Mar 25.
Artigo em Chinês | MEDLINE | ID: mdl-30919380

RESUMO

OBJECTIVE: To explore the feasibility and safety of Da Vinci robot-assisted transanal total mesorectal excision (taTME). METHODS: From May 2017 to July 2018, six rectal cancer patients underwent Da Vinci robot-assisted taTME at our hospital. The clinical data and short-term follow-up results were retrospectively analyzed. SURGICAL PROCEDURE: The patient was placed in a Trendelenburg lithotomy position and sutured with purse string 1-2 cm from the anus to the distal end of the tumor. A self-made platform for transanal surgery was installed and the robot was connected. The rectum was transected circumferentially 0.5 cm from the distal end of the purse. The robot entered the " holy plane" and separated upward between the visceral parietal fasciae to the level of the third sacrum posteriorly and the peritoneal refcection anteriorly. The abdominal trocar was repositioned and connected to the robot. Through the abdominal cavity, the Toldt space of the posterior sigmoid mesentery was entered, and the D3 lymph nodes were dissected proximally. Separation was performed distally to join the perineal approach. Specimen was pulled out from the anus and excised. The cut end of sigmoid colon was anastomosed with the distal rectum or anal canal. Operative status, postoperative pathology and short-term efficacy were analyzed. Mesorectum of specimen was evaluated as complete, near complete and incomplete according to the Nagtegaal criteria. Anastomotic leakage was evaluated according to the criteria developed by the International Rectal Cancer Research Group. RESULTS: All the 6 patients received Da Vinci robot-assisted taTME and sigmoid-anal anastomosis. In the 6 patients, 3 were male and 3 female; mean age was (62.6±2.6) years old; body mass index was (20.5±3.0) kg/m2; distance from tumor to anal edge was (39.4±12.0) mm; length of tumor was (33.6±9.2) mm. Four patients received neoadjuvant therapy before surgery. All the patients completed operations successfully without conversion to laparotomy perioperative, severe complications or death. The mean total operative time was (245.8±24.2) minutes; transition interval of two procedures was (21.2±2.6) minutes; time of transanal robotic dissection of mesorectum was (72.3±15.2) minutes; intra-operative blood loss was (86.7±59.9) ml; the height of anastomosis was (16.0±6.1) mm. There were no intra-operative complications including accidental hemorrhage or urethral injury in any patients. The length of the specimens was (177.0±33.3) mm, and the mesorectum was complete in 5 cases, and near complete in 1 case. The mean distal margin was (20.2±3.2) mm, and the proximal, distal and circumferential margins were all negative. Postoperative pathological staging: T0N0 in 1 case, T0N1 in 1 case , T2N0 in 2 cases , T4N1 in 1 case, T3N0 in 1 case. The former 5 cases received clear fluit diet on the first day, and received fluid diet on the second day after operation. The drainage tube was removed 3 to 6 days after operation. The postoperative hospital stay was 5 to 7 days. The sixth case developed grade B anastomotic leakage on the third day after operation and healed by conservative treatment. No postoperative death, and no serious complications such as intra-abdominal hemorrhage, intestinal obstruction were found. All the patients were followed up for 5 to 19 months, and no local recurrence and death were observed. CONCLUSION: The robotic system is safe and feasible for taTME procedure in rectal cancer with good short-term efficacy. However, the long-term outcomes require further observation.


Assuntos
Procedimentos Cirúrgicos Robóticos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Retais , Reto , Estudos Retrospectivos
15.
Life Sci Alliance ; 2(2)2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30910806

RESUMO

Spinal muscular atrophy (SMA), the leading genetic cause of infant mortality, is caused by reduced levels of functional survival motor neuron (SMN) protein. To identify therapeutic agents for SMA, we established a versatile SMN2-GFP reporter line by targeting the human SMN2 gene. We then screened a compound library and identified Z-FA-FMK as a potent candidate. Z-FA-FMK, a cysteine protease inhibitor, increased functional SMN through inhibiting the protease-mediated degradation of both full-length and exon 7-deleted forms of SMN. Further studies reveal that CAPN1, CAPN7, CTSB, and CTSL mediate the degradation of SMN proteins, providing novel targets for SMA. Notably, Z-FA-FMK mitigated mitochondriopathy and neuropathy in SMA patient-derived motor neurons and showed protective effects in SMA animal model after intracerebroventricular injection. E64d, another cysteine protease inhibitor which can pass through the blood-brain barrier, showed even more potent therapeutic effects after subcutaneous delivery to SMA mice. Taken together, we have successfully established a human SMN2 reporter for future drug discovery and identified the potential therapeutic value of cysteine protease inhibitors in treating SMA via stabilizing SMN proteins.

16.
Talanta ; 194: 680-688, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30609590

RESUMO

The prospect of wielding surface-enhanced Raman spectroscopy (SERS) as a powerful technique for ultrasensitive detection of organic molecules in wastewater has received extensive attention in environmental surveillance. Based on ultraviolet (UV, 405 nm) laser irradiation of ZnO nanorods in HAuCl4 solution, ZnO@Au nanorods with controllable Au nanoparticles were successfully fabricated and established as an advanced SERS-based substrate. The reduction of Au ions was driven by the generation of electron-hole pairs via UV laser excitation of semiconductor-based nanomaterials, resulting in the moderate overgrowth of Au nanoparticles on the ZnO nanorods. The Au composition-dependent SERS analysis of crystal violet (CV) molecules revealed that the ZnO@Au nanorods with 16.21% Au contents exhibited optimized SERS activity in comparison with other nano-substrates in this paper. Furthermore, the detection limit of light-resistant methyl blue (MB) dye molecules was achieved at nanomole (nM) level of 10-9 M (0.8 µg/L), providing ultrasensitive detection of organic pollution in wastewater. Even after twenty recycles, the excellent reusability of this novel substrate with 65% original SERS intensity was achieved by subsequently eliminating the residual MB molecules via photocatalytic degradation. Therefore, the as-prepared ZnO@Au nanorods can serve as a cost-effective, clean, reusable and active SERS substrate for ultrasensitive monitoring of light-resistant organic pollutant in natural ecosystems.

17.
Spectrochim Acta A Mol Biomol Spectrosc ; 209: 241-247, 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30414572

RESUMO

Ultrasensitive detection of pesticide residues on agricultural products using surface-enhanced Raman spectroscopy (SERS) is of significant interest in food security. Herein, worm-like AuAg nanochains with highly interconnected ultrafine (~6.2 nm) bimetallic particles were developed as an excellent SERS nanosensor via laser-assisted strategy. The SERS detection limit of thiram molecules on apple surfaces is about 10-7 M (0.03 ppm), which is about 200 times lower than the maximal residue limit (MRL, 7 ppm) in fruit prescribed by the U.S. Environmental Protection Agency (EPA). Importantly, the established excellent linear relationships between the SERS intensities and thiram concentrations can sensitively monitor the slight variation of pesticide residues in agriculture.


Assuntos
Frutas/química , Ouro/química , Malus/química , Nanopartículas Metálicas/química , Resíduos de Praguicidas/análise , Prata/química , Análise Espectral Raman/métodos , Limite de Detecção , Propriedades de Superfície
18.
Cell Rep ; 25(13): 3786-3799.e4, 2018 12 26.
Artigo em Inglês | MEDLINE | ID: mdl-30590049

RESUMO

Both innate and adaptive immune cells are involved in the pathogenesis of nonalcoholic steatohepatitis (NASH), but the crosstalk between innate and adaptive immunity is largely unknown. Here we show that compared with WT mice, OX40-/- mice exhibit decreased liver fat accumulation, lobular inflammation, and focal necrosis after feeding with diets that induce NASH. Mechanistically, OX40 deficiency suppresses Th1 and Th17 differentiation, and OX40 deficiency in T cells inhibits monocyte migration, antigen presentation, and M1 polarization. Soluble OX40 stimulation alone upregulates antigen presentation, chemokine receptor expression, and proinflammatory cytokine secretion by liver monocytes. Furthermore, plasma soluble OX40 levels are positively associated with NASH in humans, suggesting clinical relevance of the findings. In conclusion, we show a mechanism for T cell regulation of innate immune cells. OX40 is a key regulator of both intrahepatic innate and adaptive immunity, generates two-way signals, and promotes both proinflammatory monocyte and macrophage and T cell function, resulting in NASH development.


Assuntos
Imunidade Adaptativa , Imunidade Inata , Hepatopatia Gordurosa não Alcoólica/imunologia , Hepatopatia Gordurosa não Alcoólica/patologia , Receptores OX40/metabolismo , Animais , Apresentação do Antígeno , Diferenciação Celular , Sobrevivência Celular , Citocinas/metabolismo , Regulação para Baixo , Humanos , Mediadores da Inflamação/metabolismo , Fígado/imunologia , Fígado/patologia , Ativação Linfocitária/imunologia , Camundongos Endogâmicos C57BL , Monócitos/patologia , Hepatopatia Gordurosa não Alcoólica/sangue , Receptores OX40/sangue , Receptores OX40/deficiência , Solubilidade , Linfócitos T/imunologia
19.
Mediators Inflamm ; 2018: 3802324, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30402039

RESUMO

Objective: This study was aimed at investigating whether sevoflurane inhalation induced cognitive impairment in rats with a possible mechanism involved in the event. Methods: Thirty-two rats were randomly divided into four groups of normal saline (NS) + O2, NS + sevoflurane (sevo), amyloid-ß peptide (Aß) + O2, and Aß + sevo. The rats in the four groups received bilateral intrahippocampus injections of NS or Aß. The treated hippocampus was harvested after inhaling 30% O2 or 2.5% sevoflurane. Evaluation of cognitive function was performed by Morris water maze (MWZ) and an Aß 1-42 level was determined by ELISA. Protein and mRNA expressions were executed by immunohistochemical (IHC) staining, Western blotting, and qRT-PCR. Results: Compared with the NS-treated group, sevoflurane only caused cognitive impairment and increased the level of Aß 1-42 of the brain in the Aß-treated group. Sevoflurane inhalation but not O2 significantly increased glial fibrillary acidic protein (GFAP) and ionized calcium-binding adaptor molecule (IBA)1 expression in Aß-treated hippocampus of rats. Expression levels for Bcl-xL, caspase-9, receptor for advanced glycation end products (RAGE) and brain-derived neurotrophic factor (BDNF) were significantly different in quantification of band intensity between the rats that inhaled O2 and sevoflurane in Aß-treated groups (all P < 0.05). Interleukin- (IL-) 1ß, nuclear factor-κB (NF-κB), and inducible nitric oxide synthase (iNOS) mRNA expression increased after the rats inhaled sevoflurane in the Aß-treated group (both P < 0.01). There were no significant differences in the change of GFAP, IBA1, Bcl-xL, caspase-9, RAGE, BDNF, IL-1ß, NF-κB, and iNOS in the NS + O2 and NS + sevo group (all P > 0.05). Conclusion: Sevoflurane exacerbates cognitive impairment induced by Aß 1-40 in rats through initiating neurotoxicity, neuroinflammation, and neuronal apoptosis in rat hippocampus.

20.
Appl Opt ; 57(27): 7778-7781, 2018 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-30462041

RESUMO

The characteristics of the electromagnetically induced transparency (EIT) analog exposed under different illumination powers have been investigated theoretically and experimentally. The EIT analog is composed of a fixed aluminum structure fabricated on the silicon substrate. It was found that the resonance degree of the transparent window displayed a decreasing trend, and a blueshift phenomenon emerged by increasing the powers of the laser. Similarly, the properties of the time delay under different illumination powers have also been researched. The realization of the tuning effect may provide a possible choice for the modulation of the slow light devices.

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