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1.
Chin Herb Med ; 14(4): 583-591, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36405065

RESUMO

Objective: To elucidate the anti-inflammatory mechanism of Reduning Injection (RDN) by analyzing the potential biomarkers and metabolic pathways of the carrageenan-induced inflammatory model from the overall metabolic level. Methods: Rat inflammatory model was established by carrageenan. UPLC-Q-TOF/MS was used to detect and analyze changes of endogenous metabolites in the serum and urine of carrageenan-induced inflammatory rats. Combined with multivariate analysis and databases analysis, inflammatory-related potential biomarkers were screened and identified to analyze possible metabolic pathways. The reliability and biological significance of these biomarkers was verified by metabolic network analysis and correlation analysis with pharmacodynamic indicators. Results: A total of 16 potential biomarkers were screened and identified by multivariate analysis and metabolite databases, among which 13 species could be adjusted by RDN. The metabolism pathway analysis revealed that histidine metabolism, sphingolipid metabolism, and tyrosine metabolism were greatly disturbed. Their biomarkers involved urocanic acid, sphingosine, and norepinephrine, all of which showed a callback trend after RDN treatment. The three biomarkers had a certain correlation with some known inflammatory-related small molecules (histamine, arachidonic acid, Leukotriene B4, and PGE2) and pharmacodynamic indicators (IL-6, IL-1ß, PGE2 and TNF-α), which indicated that the selected biomarkers had certain reliability and biological significance. Conclusion: RDN has a good regulation of the metabolic disorder of endogenous components in carrageenan-induced inflammatory rats. And its anti-inflammatory mechanism is mainly related to the regulation of amino acid and lipid metabolism. This research method is conducive to the interpretation of the overall pharmacological mechanism of Chinese medicine.

2.
World J Gastrointest Surg ; 14(10): 1107-1119, 2022 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-36386400

RESUMO

BACKGROUND: Pylorus and vagus nerve-preserving gastrectomy (PPG) is a function-preserving surgery for early gastric cancer (GC) that has gained considerable interest in the recent years. The operative technique performed using the Da Vinci Xi robot system is considered ideal for open and laparoscopic surgery. AIM: To introduce Da Vinci Xi robot-assisted PPG (RAPPG)-based operative procedure and technical points as well as report the initial experience based on the clinical pathology data of eight cases of early GC. METHODS: Da Vinci Xi robot-assisted pylorus and vagus nerve-preserving gastrectomy (RAPPG) was performed for 11 consecutive patients with middle GC from December 2020 to July 2021. Outcome measures were postoperative morbidity, operative time, blood loss, number of lymph nodes harvested, postoperative hospital stay, time to first flatus, time to diet, and resection margins. RESULTS: Eight of the 11 patients who were pathologically diagnosed with early GC were enrolled in a retrospective study to assess the feasibility and safety of RAPPG. The mean operative time, mean blood loss, mean number of lymph nodes harvested, length of preserved pylorus canal, distal margin, and proximal margin were 330.63 ± 47.24 min, 57.50 ± 37.70 mL, 18.63 ± 10.57, 3.63 ± 0.88 cm, 3.50 ± 1.31 cm, and 3.63 ± 1.19 cm, respectively. None of the cases required conversion to laparotomy. Postoperative complications occurred in two (25.0%) patients. Postoperative complications were hyperamylasemia and gastric stasis in one case and incision infection in the other. Time to first flatus was 3.75 ± 2.49 d after the operation, and postoperative hospital stay was 10.13 ± 4.55 d. CONCLUSION: The core technique in the Da Vinci Xi RAPPG is lymph node dissection and the anatomic method of the nerve. Robotic surgical procedures are feasible and safe. With the progress of surgical technology, optimization of medical insurance structure, and emergence of evidence-based medicine, automated surgery systems will have a broad application in clinical treatment.

3.
Sci Rep ; 12(1): 18454, 2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36323864

RESUMO

Soya bean sprout is a nutrient-abundant vegetable. However, enzymatic browning of soya bean sprouts during storage remains a challenge. In this study, the effects of treatment with MnCl2 or ZnCl2 on the browning index, antioxidant nutrient accumulation, total antioxidant capacity and enzyme activities of phenylalanine ammonia-lyase (PAL), polyphenol oxidase (PPO), peroxidase (POD), superoxide dismutase (SOD) and catalase (CAT) were investigated in soya bean sprouts after storage at 4 °C and 90% relative humidity for 0, 7, 14 and 21 days. The results showed that postharvest treatment with 1, 2 and 10 mM MnCl2 or ZnCl2 profoundly retarded enzymatic browning in soya bean sprouts to different extents. Compared with the control, the 10 mM MnCl2 and ZnCl2 treatments drastically enhanced ascorbic acid, total thiol and phenolic content, and enhanced FRAP (ferric-reducing ability of plasma) antioxidant capacity in stored soya bean sprouts. Moreover, the MnCl2 and ZnCl2 treatments enhanced SOD, CAT and PAL but decreased PPO and POD activities compared with the control. In addition, the Mn and Zn content in soya bean sprouts significantly increased, by approximately two- to threefold, compared with the control. This study provides a new method for improving the nutrient quality of soya bean sprouts based on postharvest Mn or Zn supplementation.


Assuntos
Antioxidantes , Catecol Oxidase , Fenóis , Fenilalanina Amônia-Liase , Superóxido Dismutase
4.
Sci Total Environ ; 858(Pt 3): 160040, 2022 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-36347280

RESUMO

Ocean acidification potentially influences the biotoxicity of metals and the antioxidant defense systems of marine organisms. This study investigated how pCO2-driven seawater acidification (SA) affected aqueous-phase copper (Cu) toxicity in the juvenile flounder Paralichthys olivaceus from the perspective of hepatic oxidative stress and damage to better understand the mechanisms underlying the biological effects produced by the two stressors. Fish were exposed to aqueous-phase Cu at relevant ambient and polluted concentrations (0, 5, 10, 50, 100 and 200 µg L-1) at different pH levels (no SA: pH 8.10; moderate SA: pH 7.70, pCO2 ∼1353.89 µatm; extreme SA: pH 7.30, pCO2 ∼3471.27 µatm) for 28 days. A battery of biomarkers in the livers was examined to investigate their roles in antioxidant defense and detoxification in response to coexposure. Hepatic Cu accumulation (30.22-184.90 mg kg-1) was positively correlated with Cu concentrations. The biomarkers responded adaptively to different redox states following SA and Cu exposure. In unacidified seawater, increases in Cu concentrations significantly induced hepatic lipid peroxidation (LPO, by up to 27.03 %), although compensatory responses in antioxidant defenses and detoxification were activated. Moderate SA helped maintain hepatic redox homeostasis and alleviated LPO through different defense strategies, depending on Cu concentrations. Under extreme SA, antioxidant-based defenses were activated to cope with oxidative stress at ambient-low Cu concentrations but failed to defend against Cu toxicity at polluted Cu levels, and LPO (by up to 63.90 %) was significantly induced. Additionally, thiols (GSH and MT) responded actively to cope with Cu toxicity under SA. SOD, CAT, EROD, and GST were also sensitively involved in defending against hepatic oxidative stress during coexposure. These findings highlight the notable interactive effects of SA and Cu and provide a basis for understanding antioxidant-based defenses in marine fish confronting environmental challenges.

5.
Langmuir ; 38(48): 14969-14980, 2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36394474

RESUMO

Covalent grafting of dielectric films containing polyhedral oligomeric silsesquioxane (POSS) on the surface of Cu(111) is performed by a one-step electrochemical reduction of diazonium salts. This method is efficient and economic and performs in a proton-polar solvent of deionized water and tetrahydrofuran (THF), where the monomer employs an octavinylsilsesquioxane (OVS) containing a POSS core. The eight vinyl bonds contained in OVS are used to participate in aryl radical-initiated polymerization reactions to form films. The formed film is dense and covers the copper surface completely and uniformly. The thickness of the film can be controlled by adjusting the reaction time. The components of the films are mainly polynitrophenyl (PNP) or polyaminophenyl (PAP) as well as poly(octavinylsilsesquioxane) (POVS), and the POVS content could be adjusted by the applied voltage. The introduction of POSS prevents the copper surface from being oxidized and often gives the film good properties such as good dielectric properties, mechanical properties, and thermal properties. In addition, the presence of Cu-O-C and Cu-C bonds between the film and copper interface is confirmed at different film thicknesses by X-ray photoelectron spectroscopy (XPS), which allowed the construction of covalent bonds between metal and nonmetal, further enhancing the bonding between the film and copper. Organic films prepared by electrochemical reduction of diazonium salts using OVS as a monomer will have potential significance for the future development of the electronics industry.

6.
Artigo em Inglês | MEDLINE | ID: mdl-36215380

RESUMO

This article focuses on the fixed-time formation control problem for nonlinear multiagent systems (MASs) with dynamic uncertainties and limited communication resources. Under the framework of the backstepping method, a time-varying formation function is introduced in the controller design. To attain the prescribed transient and steady-state performance of MASs, a fixed-time prescribed performance function (FTPPF) is designed and the further coordinate transformation addressing the zero equilibrium point problem is removed. To achieve better approximating performance, a neural network (NN)-based composite dynamic surface control (CDSC) strategy is proposed, where the CDSC scheme is consisted of prediction errors and serial-parallel estimation models. According to the signals generated by the estimation models, disturbance observers are established to overcome the difficulty from approximating errors and mismatched disturbances. Moreover, an improved dynamic event-triggered mechanism and varying threshold parameters are constructed to reduce the signal transmission frequency. Via the Lyapunov stability theory, all the signals in the closed-loop system are semi-globally uniformly ultimately bounded. Finally, the simulation results verify the effectiveness of the developed CDSC strategy.

7.
Animals (Basel) ; 12(20)2022 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-36290192

RESUMO

Too high or too low temperature in the sheep house will directly threaten the healthy growth of sheep. Prediction and early warning of temperature changes is an important measure to ensure the healthy growth of sheep. Aiming at the randomness and empirical problem of parameter selection of the traditional single Extreme Gradient Boosting (XGBoost) model, this paper proposes an optimization method based on Principal Component Analysis (PCA) and Particle Swarm Optimization (PSO). Then, using the proposed PCA-PSO-XGBoost to predict the temperature in the sheep house. First, PCA is used to screen the key influencing factors of the sheep house temperature. The dimension of the input vector of the model is reduced; PSO-XGBoost is used to build a temperature prediction model, and the PSO optimization algorithm selects the main hyperparameters of XGBoost. We carried out a global search and determined the optimal hyperparameters of the XGBoost model through iterative calculation. Using the data of the Xinjiang Manas intensive sheep breeding base to conduct a simulation experiment, the results show that it is different from the existing ones. Compared with the temperature prediction model, the evaluation indicators of the PCA-PSO-XGBoost model proposed in this paper are root mean square error (RMSE), mean square error (MSE), coefficient of determination (R2), mean absolute error (MAE) , which are 0.0433, 0.0019, 0.9995, 0.0065, respectively. RMSE, MSE, and MAE are improved by 68, 90, and 94% compared with the traditional XGBoost model. The experimental results show that the model established in this paper has higher accuracy and better stability, can effectively provide guiding suggestions for monitoring and regulating temperature changes in intensive housing and can be extended to the prediction research of other environmental parameters of other animal houses such as pig houses and cow houses in the future.

8.
RSC Adv ; 12(42): 27546-27549, 2022 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-36276018

RESUMO

A novel and efficient copper-catalyzed strategy for the synthesis of diverse pyridines through the [3+3] annulation of ketones with oxime acetates has been reported. It is very convenient to obtain various unsymmetrical 2,6-diarylpyridines by changing different substrates. The rare copper-catalyzed direct difunctionalization of saturated ketones for the synthesis of nitrogen heterocycles is developed. This protocol has excellent functional group tolerance, readily available raw materials, high chemoselectivity and broad substrate scope.

9.
Cancer Med ; 2022 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-36208017

RESUMO

LMB-100 is a novel immune-conjugate (immunotoxin) that targets mesothelin. A phase 1/2 clinical trial was conducted (NCT02810418) with primary objectives assessing the safety and efficacy of LMB-100 ± nab-paclitaxel. Participant blood samples were analyzed for changes in serum cytokines and circulating immune cell subsets associated with response or toxicity. On Arm A, participants (n = 20) received standard 30-minute LMB-100 infusion with nab-paclitaxel. Although clinical efficacy was observed, the combination caused intolerable capillary leak syndrome (CLS), a major toxicity of unclear etiology that affects many immunotoxin drugs. Participants developing CLS experienced rapid elevations in IFNγ and IL-8 compared to those without significant CLS, along with midcycle increases in Ki-67- CD4 T cells that were CD38, HLA-DR, or TIM3 positive. Additionally, a strong increase in activated CD4 and CD8 T cells and a concurrent decrease in Tregs were seen in the single Arm A patient achieving a partial response. In Arm B, administration of single agent LMB-100 to participants (n = 20) as a long infusion given over 24-48 h was investigated based on pre-clinical data that this format could reduce CLS. An optimal dose and schedule of long infusion LMB-100 were identified, but no clinical efficacy was observed even in patients receiving LMB-100 in combination with nab-paclitaxel. Despite this, both Arm A and B participants experienced increases in specific subsets of proliferating CD4 and CD8 T cells following Cycle 1 treatment. In summary, LMB-100 treatment causes systemic immune activation. Inflammatory and immune changes that accompany drug associated CLS were characterized for the first time.

10.
Physiol Mol Biol Plants ; 28(7): 1477-1488, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36051233

RESUMO

Drought affects the normal growth and development of soybeans. Melatonin reportedly alleviates drought stress-induced growth inhibition and plant injury, thus, its foliar application presumably has considerable potential in agriculture. However, few studies have investigated the mechanism responsible for its effects on soybean nitrogen metabolism. In this study, pot culture and plant physiological detection, qPCR, and other methods were used for analysis. The purpose of this study was to explore the effects of melatonin and melanin on glutathione metabolism. The results showed that drought stress led to an increase in soluble protein and proline content, concomitantly with a decrease in the activity of nitrogen metabolism-related key enzymes, an increase in inorganic nitrogen content, and a reduction in nitrogen accumulation and transport. Exogenous melatonin application under drought stress significantly increased the expression of key genes involved in nitrogen metabolism and the activity of key enzymes including, GOGAT, NR, Gs and GDH. Enhanced enzyme activity promotes the conversion of nitrate nitrogen in plants, increases proline, soluble protein, and ureide contents, and, consequently, nitrogen accumulation. Altogether, these changes were conducive to greater nitrogen assimilation and transport. Therefore, under drought stress, melatonin application upregulated key genes involved in nitrogen metabolism, thereby enhancing the activity of related enzymes and restoring growth, stable biomass production. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-022-01219-y.

11.
J Pharm Biomed Anal ; 220: 115005, 2022 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-36087496

RESUMO

Sinomenium acutum stem is widely used to treat rheumatoid arthritis, gout, ankylosing spondylitis and other diseases in China. However, its metabolism in vivo is still unclear. In this study, UPLC-Q-TOF/MS was used to analyze the main components and their metabolites in rats after oral administration of Sinomenium acutum stem extract. A total of 41 compounds were identified from the ethanol extract of Sinomenium acutum stem based on the established database and the reference substance; a total of 25 prototype components and 107 metabolites (74 phase I metabolites and 33 phase II metabolites) were speculated and identified in the plasma, urine, bile and feces of rats administered. The metabolic pathways included hydroxylation, demethylation, dehydrogenation, glucuronidation and acetylation. In conclusion, this study revealed the metabolism of Sinomenium acutum stem in vivo, which may provide a better basis for the study of Sinomenium acutum stem and provide useful chemical information on the material basis and pharmacological mechanism of drug efficay.


Assuntos
Alcaloides , Medicamentos de Ervas Chinesas , Administração Oral , Alcaloides/análise , Animais , Bile/metabolismo , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/química , Etanol/análise , Fezes/química , Ratos , Sinomenium
13.
Front Cell Neurosci ; 16: 992520, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36159391

RESUMO

The neural stem cells (NSCs) in the ventricular-subventricular zone of the adult mammalian spinal cord may be of great benefit for repairing spinal cord injuries. However, the sources of NSCs remain unclear. Previously, we have confirmed that cerebrospinal fluid-contacting neurons (CSF-cNs) have NSC potential in vitro. In this study, we verified the NSC properties of CSF-cNs in vivo. In mouse spinal cords, Pkd2l1+ CSF-cNs localized around the central canal express NSC markers. In vitro, Pkd2l1+ CSF-cNs form a neurosphere and express NSC markers. Activation and proliferation of CSF-cNs can be induced by injection of the neurotrophic factors basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) into the lateral ventricle. Spinal cord injury (SCI) also induces NSC activation and proliferation of CSF-cNs. Collectively, our results demonstrate that Pkd2l1+ CSF-cNs have NSC properties in vivo and may be involved in SCI recovery.

14.
BMC Nephrol ; 23(1): 323, 2022 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-36171551

RESUMO

BACKGROUND: Kidney stones have become a worldwide public health problem. The purpose of this research is to study the relationship between plasma cadmium level and the prevalence of kidney stones in an adult population. METHODS: The data of this study were based on a current survey conducted from December 2018 to November 2019 in Gongcheng Yao Autonomous County, Guangxi, China. A total of 940 study subjects of the same sex and age (within 2 years of each other) according to 1:1 matching were selected for a case-control study. The diagnosis of kidney stones was based on the presence of strong light spots, patches, clusters, or bands within the renal sinus region, followed by an echo-free bundle of acoustic images. Plasma metal elements were determined by the metal plasma method. The relationship between plasma cadmium concentration and the prevalence of kidney stones was assessed using logistic regression and restricted cubic spline regression. RESULTS: The crude ratio for kidney stones in the highest quartile of plasma cadmium was 1.164 (95% CI, 1.121 to 2.324) compared with the lowest quartile. A positive correlation was found between the two (P for trend = 0.039). After adjusting for potential confounders, the ratio of plasma cadmium to kidney stones in the highest quartile was 1.606 (95% CI, 1.100 to 2.344) compared with the lowest quartile, and the findings remained unchanged. CONCLUSION: The odds of kidney stones in adults increased with increasing plasma cadmium exposure, and high plasma cadmium may be a risk factor for kidney stones.


Assuntos
Cádmio , Cálculos Renais , Adulto , Estudos de Casos e Controles , Pré-Escolar , China/epidemiologia , Humanos , Cálculos Renais/epidemiologia , Prevalência
15.
Contrast Media Mol Imaging ; 2022: 5951418, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36051929

RESUMO

This research aimed to investigate the diagnostic effect of computed tomography (CT) images based on a deep learning double residual convolution neural network (DRCNN) model on chronic obstructive pulmonary disease (COPD) and the related risk factors for COPD. The questionnaire survey was conducted among 980 permanent residents aged ≥ 40 years old. Among them, 84 patients who were diagnosed with COPD and volunteered to participate in the experiment and 25 healthy people were selected as the research subjects, and all of them underwent CT imaging scans. At the same time, an image noise reduction model based on the DRCNN was proposed to process CT images. The results showed that 84 of 980 subjects were diagnosed with COPD, and the overall prevalence of COPD in this epidemiological survey was 8.57%. Multivariate logistic regression model analysis showed that the regression coefficients of COPD with age, family history of COPD, and smoking were 0.557, 0.513, and 0.717, respectively (P < 0.05). The diagnostic sensitivity, specificity, and accuracy of DRCNN-based CT for COPD were greatly superior to those of single CT and the difference was considerable (P < 0.05). In summary, advanced age, family history of COPD, and smoking were independent risk factors for COPD. CT based on the DRCNN model can improve the diagnostic accuracy of simple CT images for COPD and has good performance in the early screening of COPD.


Assuntos
Aprendizado Profundo , Doença Pulmonar Obstrutiva Crônica , Adulto , Progressão da Doença , Humanos , Programas de Rastreamento/efeitos adversos , Programas de Rastreamento/métodos , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Fatores de Risco , Tomografia Computadorizada por Raios X/métodos
16.
Huan Jing Ke Xue ; 43(8): 3998-4007, 2022 Aug 08.
Artigo em Chinês | MEDLINE | ID: mdl-35971698

RESUMO

To explore the periphytic algae community structure in the Yangtze River basin, samples were collected from 130 sampling sites, including the source to the estuary along the mainstream of the Yangtze River, eight primary tributaries, and the tributary of the Three Gorges area. The periphytic algae densities of different areas in the mainstream of the Yangtze River ranked from high to low were the upstream area, source area, middle and lower area, and the Jinsha River. The high periphytic algae density in the upstream area was associated with the shift in nutrition level, and the high periphytic algae density in the source area was associated with human activity. The spatial pattern of the periphytic algae community in the whole main stream from west to east presented the alternating dominance of Bacillariophyta and Cyanophyta; the Bacillariophyta (Navicula) had a competitive advantage in the main stream, and the distribution of the periphytic algae community was driven by total nitrogen, total phosphorus, and pH. For the tributary of the Yangtze River, the periphytic algae density in the Three Gorges tributary area was far higher than those in the eight primary tributaries; the periphytic algae community was dominated by Cyanophyta (Lyngbya), which had a competitive advantage in the tributaries of the Yangtze River. The distribution of the periphytic community was driven by dissolved oxygen and pH. According to the diversity analysis and assessment, the periphytic algae community in the source area showed lower species richness and higher evenness, thus leading to a high α-diversity and good assessment result (mesosaprobic zone). The middle and lower reaches of the Yangtze River also showed the same assessment result, the mesosaprobic zone. However, the community evenness of the middle and lower reaches was significantly lower than that of the source area, thus making the middle and lower reaches of the Yangtze River have a significantly lower α-diversity than that of the source area. All areas of the Yangtze River showed good water quality assessment; however, different areas had different WQI index numbers, and the assessment results of the WQI index were inconsistent with the results of the aquatic assessment. Therefore, a comprehensive assessment of aquatic ecosystem health should use both aquatic assessments and water quality assessments.


Assuntos
Cianobactérias , Diatomáceas , China , Ecossistema , Monitoramento Ambiental/métodos , Humanos , Fósforo/análise , Rios/química , Qualidade da Água
17.
Viruses ; 14(8)2022 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-36016401

RESUMO

Chikungunya virus (CHIKV) is a mosquito-borne virus. The emergence of CHIKV infection has raised global concern, and there is a growing need to develop safe and effective vaccines. Here, adenovirus 5 was used as the vaccine vector to construct recombinant adenoviruses expressing CHIKV E2, E1, and E2-6K-E1, respectively. And then the immunogenicity and protective efficiency against CHIKV were evaluated in BALB/c mice. Compared to the ad-wt control group, all three vaccines elicited significant humoral and cellar immune responses. The levels of neutralizing antibodies in the rAd-CHIKV-E2-6K-E1 and rAd-CHIKV-E2 groups both reached 1:256, which were 3.2 times higher than those in the rAd-CHIKV-E1 group. Furthermore, the levels of lymphocyte proliferation in rAd-CHIKV-E2-6K-E1 group were the highest. Besides, the concentrations of IFN-γ and IL-4 in mice immunized with rAd-CHIKV-E2-6K-E1 were 1.37 and 1.20 times higher than those in ad-wt immunized mice, respectively. After the challenge, mice in the rAd-CHIKV-E2-6K-E1 and rAd-CHIKV-E2 groups lost 2% of their body weight compared with 5% in the ad-wt control group. And low viral loads were detected in the heart, kidney, and blood of mice immunized with rAd-CHIKV-E2-6K-E1 and rAd-CHIKV-E2 at 3-5 dpc, which decreased by 0.4-0.7 orders of magnitude compared with the ad-wt control. Overall, these data suggest that the recombinant adenovirus is a potential candidate vaccine against CHIKV.


Assuntos
Infecções por Adenoviridae , Vacinas contra Adenovirus , Febre de Chikungunya , Vírus Chikungunya , Vacinas Virais , Adenoviridae/genética , Animais , Anticorpos Antivirais , Febre de Chikungunya/prevenção & controle , Vírus Chikungunya/genética , Camundongos , Mosquitos Vetores , Vacinas Sintéticas/genética , Proteínas do Envelope Viral , Vacinas Virais/genética
18.
Cell Rep ; 40(5): 111156, 2022 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-35926466

RESUMO

N6-methyladenosine (m6A), the most common form of RNA modification, controls CD4+ T cell homeostasis by targeting the IL-7/STAT5/SOCS signaling pathways. The role of m6A modification in unconventional T cell development remains unknown. Using mice with T cell-specific deletion of RNA methyltransferase METTL14 (T-Mettl14-/-), we demonstrate that m6A modification is indispensable for iNKT cell homeostasis. Loss of METTL14-dependent m6A modification leads to the upregulation of apoptosis in double-positive thymocytes, which in turn decreases Vα14-Jα18 gene rearrangements, resulting in drastic reduction of iNKT numbers in the thymus and periphery. Residual T-Mettl14-/- iNKT cells exhibit increased apoptosis, impaired maturation, and decreased responsiveness to IL-2/IL-15 and TCR stimulation. Furthermore, METTL14 knockdown in mature iNKT cells diminishes their cytokine production, correlating with increased Cish expression and decreased TCR signaling. Collectively, our study highlights a critical role for METTL14-dependent-m6A modification in iNKT cell development and function.


Assuntos
Células T Matadoras Naturais , Animais , Diferenciação Celular/genética , Metiltransferases , Camundongos , Camundongos Endogâmicos C57BL , Células T Matadoras Naturais/metabolismo , RNA/metabolismo , Receptores de Antígenos de Linfócitos T/metabolismo
19.
Front Surg ; 9: 898579, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35774387

RESUMO

Introduction: While tranexamic acid (TXA) is widely used in patients with acute type A aortic dissection (ATAAD) who undergo surgical repair to reduce blood loss and transfusion requirement, the optimal dosage of TXA is unknown in these patients. Materials and Methods: This was a retrospective cohort study that compared high-dose (>50 mg/kg) and low-dose TXA (≤50 mg/kg) in patients with ATAAD who underwent surgical repair. Propensity score matching (PSM) was performed between the two groups and results were analyzed in matched cases. The primary outcome was postoperative blood loss within 3 days after surgery. The secondary outcomes were total blood loss after surgery and perioperative blood transfusion, and safety outcomes were also assessed. Results: Through medical record screening, 529 patients were identified. After PSM, 196 patients in the high-dose group and 196 patients in the low-dose group were matched and included in the final analysis. Postoperative blood loss in 3 days after surgery was 940 mL (710-1,010 mL) in the low-dose group and 695 mL (620-860 mL) in the high-dose group. The difference was statistically significant (P < 0.001). Total postoperative blood loss was also statistically less in the high-dose group compared to the low-dose group (1,890 mL (1,410-2,100 mL) vs. 2,040 mL (1,460-2,320 mL), P = 0.032). No difference was found between the two groups in transfusion and safety outcomes. Conclusion: In ATAAD patients who underwent surgical repair, high-dose TXA significantly reduced postoperative blood loss compared to low-dose TXA, while no difference in transfusion or adverse events was found.

20.
Am J Chin Med ; 50(6): 1565-1597, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35902245

RESUMO

Currently, therapies for ischemic stroke are limited. Ginkgolides, unique Folium Ginkgo components, have potential benefits for ischemic stroke patients, but there is little evidence that ginkgolides improve neurological function in these patients. Clinical studies have confirmed the neurological improvement efficacy of diterpene ginkgolides meglumine injection (DGMI), an extract of Ginkgo biloba containing ginkgolides A (GA), B (GB), and K (GK), in ischemic stroke patients. In the present study, we performed transcriptome analyses using RNA-seq and explored the potential mechanism of ginkgolides in seven in vitro cell models that mimic pathological stroke processes. Transcriptome analyses revealed that the ginkgolides had potential antiplatelet properties and neuroprotective activities in the nervous system. Specifically, human umbilical vein endothelial cells (HUVEC-T1 cells) showed the strongest response to DGMI and U251 human glioma cells ranked next. The results of pathway enrichment analysis via gene set enrichment analysis (GSEA) showed that the neuroprotective activities of DGMI and its monomers in the U251 cell model were related to their regulation of the sphingolipid and neurotrophin signaling pathways. We next verified these in vitro findings in an in vivo cuprizone (CPZ, bis(cyclohexanone)oxaldihydrazone)-induced model. GB and GK protected against demyelination in the corpus callosum (CC) and promoted oligodendrocyte regeneration in CPZ-fed mice. Moreover, GB and GK antagonized platelet-activating factor (PAF) receptor (PAFR) expression in astrocytes, inhibited PAF-induced inflammatory responses, and promoted brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) secretion, supporting remyelination. These findings are critical for developing therapies that promote remyelination and prevent stroke progression.


Assuntos
Doenças Desmielinizantes , Diterpenos , AVC Isquêmico , Fármacos Neuroprotetores , Acidente Vascular Cerebral , Animais , Astrócitos/metabolismo , Doenças Desmielinizantes/tratamento farmacológico , Doenças Desmielinizantes/metabolismo , Diterpenos/farmacologia , Diterpenos/uso terapêutico , Células Endoteliais , Ginkgo biloba , Ginkgolídeos/metabolismo , Ginkgolídeos/farmacologia , Ginkgolídeos/uso terapêutico , Humanos , Lactonas/farmacologia , Camundongos , Fármacos Neuroprotetores/farmacologia , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/genética
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