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In this study, we assessed the therapeutic effects of Macleaya cordata (Willd). R. Br.-derived protopine-type alkaloids (MPTAs) in a mouse model of lipopolysaccharide (LPS)-induced intestinal inflammation. The experimental design involved the allocation of mice into distinct groups, including a control group, a model group treated with 6 mg/kg LPS, a berberine group treated with 50 mg/kg berberine hydrochloride and low-, medium- and high-dose MPTA groups treated with 6, 12 and 24 mg/kg MPTAs, respectively. Histological analysis of the ileum, jejunum and duodenum was performed using Hematoxylin and Eosin (H&E) staining. Moreover, the quantification of intestinal goblet cells (GCs) was performed based on PAS staining. The serum levels of IL-1ß, IL-6, IL-8 and TNF-α were quantified using an enzyme-linked immunosorbent assay (ELISA), while the mRNA levels of TLR4, NF-κB p65, NLRP3, IL-6 and IL-1ß were assessed using quantitative PCR (qPCR). The protein levels of TLR4, Md-2, MyD88, NF-κB p65 and NLRP3 were determined using Western blotting. Furthermore, the 16S rDNA sequences of bacterial taxa were amplified and analysed to determine alterations in the gut microbiota of the mice following MPTA treatment. Different doses of MPTAs were found to elicit distinct therapeutic effects, leading to enhanced intestinal morphology and an increased abundance of intestinal GCs. A significant decrease was noted in the levels of pro-inflammatory cytokines (IL-1ß, IL-6, IL-8 and TNF-α). Additionally, the protein levels of TLR4, MyD88, NLRP3 and p-p65/p65 were markedly reduced by MPTA treatment. Furthermore, 16S rDNA sequencing analysis revealed that the administration of 24 mg/kg MPTAs facilitated the restoration of microbial composition.
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BACKGROUND: During city running or marathon races, shifts in level ground and up-and-down slopes are regularly encountered, resulting in changes in lower limb biomechanics. The longitudinal bending stiffness of the running shoe affects the running performance. PURPOSE: This research aimed to investigate the biomechanical changes in the lower limbs when transitioning from level ground to an uphill slope under different longitudinal bending stiffness (LBS) levels in running shoes. METHODS: Fifteen male amateur runners were recruited and tested while wearing three different LBS running shoes. The participants were asked to pass the force platform with their right foot at a speed of 3.3 m/s ± 0.2. Kinematics data and GRFs were collected synchronously. Each participant completed and recorded ten successful experiments per pair of shoes. RESULTS: The range of motion in the sagittal of the knee joint was reduced with the increase in the longitudinal bending stiffness. Positive work was increased in the sagittal plane of the ankle joint and reduced in the keen joint. The negative work of the knee joint increased in the sagittal plane. The positive work of the metatarsophalangeal joint in the sagittal plane increased. CONCLUSION: Transitioning from running on a level surface to running uphill, while wearing running shoes with high LBS, could lead to improved efficiency in lower limb function. However, the higher LBS of running shoes increases the energy absorption of the knee joint, potentially increasing the risk of knee injuries. Thus, amateurs should choose running shoes with optimal stiffness when running.
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Extremidad Inferior , Carrera , Zapatos , Humanos , Masculino , Fenómenos Biomecánicos/fisiología , Carrera/fisiología , Extremidad Inferior/fisiología , Adulto , Rango del Movimiento Articular/fisiología , Articulación del Tobillo/fisiología , Articulación de la Rodilla/fisiología , Adulto JovenRESUMEN
Introduction: Neuromyelitis optica spectrum disorder (NMOSD) is a central nervous system demyelinating disease. Current therapy methods, however, have limited effect on acute attacks except for intravenous methylprednisolone (IVMP). Efgartigimod is a first-in-class novel human immunoglobulin G1 (IgG1) Fc fragment approved for the treatment of generalized myasthenia gravis. Its capacity to rapidly decrease serum IgG levels, including pathogenic autoantibodies, positions it as a potentially effective option for managing the acute phase of NMOSD. Case presentation: We report the case of a 59-year-old female patient with acute NMOSD, presenting with vision loss and numbness in all four limbs. Despite an initial inadequate response to intravenous methylprednisolone (IVMP), the addition of Efgartigimod to her treatment regimen led to rapid improvement, notably including a significant reduction in serum aquaporin-4 antibody titers, total IgG levels, and inflammation cytokine levels. Furthermore, no adverse events were reported during a four-month follow-up period. Conclusion: As an adjunct to glucocorticoid therapy, Efgartigimod has proven effective and safe for this patient. However, to ascertain its potential as a novel therapeutic option for acute NMOSD, larger-scale prospective clinical trials are required.
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Effective treatment of oily wastewater, which is toxic and harmful and causes serious environmental pollution and health risks, has become an important research field. Membrane separation technology has emerged as a key area of investigation in oil-water separation research due to its high separation efficiency, low costs, and user-friendly operation. This review aims to report on the advances in the research of various types of separation membranes around emulsion permeance, separation efficiency, antifouling efficiency, and stimulus responsiveness. Meanwhile, the challenges encountered in oil-water separation membranes are examined, and potential research avenues are identified.
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Inflammatory bowel disease, a disease featured by intestinal epithelial barrier destruction and dysfunction, has been a constant threat to animal health. The primary objective of this research was to assess the impact of the extract derived from lotus leaves (LLE) on lipopolysaccharide (LPS) induced damage to the intestines in mice, as well as to investigate the fundamental mechanism involved. The LLE was prepared using ultrasonic extraction in this experiment, and the LLE total flavonoid content was 117.02 ± 10.73 mg/g. The LLE had strong antioxidant activity in vitro, as assessed by 2, 2-diphenyl-1-picrylhydrazyl, ferric reducing antioxidant power, and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) methods. In the vivo experiment, different doses of LLE (50, 100, and 200 mg/kg) were administered for 2 weeks before LPS treatment in mice. The results revealed that LLE alleviates intestinal tissue damage in LPS-induced mice. In the jejunum tissue, LLE significantly upregulated mRNA and protein expression levels of tight junction proteins, such as ZO-1, occludin, and claudin-1, and decreased the contents of the inflammatory cytokines, interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α. Furthermore, the malondialdehyde and lactate dehydrogenase contents increased by LPS in the liver were significantly reduced after administration of LLE, and the total antioxidant capacity, superoxide dismutase, and reduced glutathione decreased by LPS were remarkably increased by LLE. It was found that LLE could relieve LPS-induced oxidative stress by upregulating mRNA and protein expression of Nrf2 and HO-1 in jejunum tissue. In conclusion, LLE alleviates LPS-induced intestinal damage through regulation of the Nrf2/HO-1 signal pathway to alleviate oxidative stress, reducing inflammatory factors and increasing the expression of tight junction proteins in mice.
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Lipopolisacáridos , Lotus , Factor 2 Relacionado con NF-E2 , Estrés Oxidativo , Extractos Vegetales , Hojas de la Planta , Animales , Estrés Oxidativo/efectos de los fármacos , Lipopolisacáridos/efectos adversos , Extractos Vegetales/farmacología , Extractos Vegetales/administración & dosificación , Ratones , Hojas de la Planta/química , Lotus/química , Masculino , Factor 2 Relacionado con NF-E2/metabolismo , Factor 2 Relacionado con NF-E2/genética , Antioxidantes/farmacología , Inflamación/tratamiento farmacológico , Inflamación/inducido químicamente , Inflamación/metabolismo , Humanos , Intestinos/efectos de los fármacos , Hemo-Oxigenasa 1/metabolismo , Hemo-Oxigenasa 1/genética , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efectos de los fármacos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/inducido químicamente , Enfermedades Inflamatorias del Intestino/metabolismoRESUMEN
In this study, the effects of thermal treatments on the structural, rheological, water mobility, antioxidant, and astringency properties of proanthocyanidin (PA)-pectin binary complexes were investigated. Thermal treatments (25, 63, or 85 °C) significantly decreased the particle size but increased the molecular weight of PA-pectin complexes, which indicated that heating altered the intermolecular and intramolecular interactions between PA and pectin. The thermal treatments reduced the apparent viscosity of both pectin and PA-pectin complexes, but the presence of proanthocyanidins (PAs) increased the apparent viscosity and water mobility of the PA-pectin complexes. Antioxidant activity analysis showed that the presence of pectin slightly reduced the antioxidant activity of the PAs, but there were no significant changes in the total phenolic content and antioxidant activity after thermal treatment. Finally, we found that pectin reduced the astringency of the PAs by forming PA-pectin complexes. Moreover, the thermal treatments also significantly reduced the astringency of the PA-pectin complexes.
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Pectinas , Proantocianidinas , Pectinas/química , Antioxidantes/química , Astringentes , Viscosidad , Agua , ReologíaRESUMEN
Objective: This qualitative study aimed to understand the clinical safety, efficacy, and receptiveness of using the female condom (FC) during anal intercourse among men who have sex with men (MSM). Methods: Subjects for this study were recruited from a two-group crossover trial among MSM in Shanghai. The trial consisted of two phases, each including the use of condoms (FC vs. male condom), questionnaires, and in-depth one-on-one interviews. The two phases were separated by a washout period of 4 weeks. The minimum sample size for this study was determined in accordance with the principle of "information saturation." The qualitative data were organized and analyzed using ATLAS.ti version 7. Results: A total of 26 participants from the MSM population were recruited for this study, with 10 assuming the insertive role (i.e., "1"), 8 assuming the receptive role (i.e., "0"), and 8 being versatile (i.e., "0.5"). Each participant completed the crossover trial comprising two phases. The cumulative usage of FCs and male condoms (MCs) amounted to 115 and 127 times, respectively. During the reported sexual encounters, no participants reported incidents of condom rupture, slippage, or other malfunctions. A few participants reported experiencing slight chafing pain, primarily put forward by "0" participants. Apart from those reports, no instances of bleeding, swelling, or allergic reactions were reported. The efficiency of FC in disease prevention, the sexual partner's willingness to use FC, the freshness of FC, and positive sexual experiences were the main reasons for the consistent use of FC for anal sex. Discomfort and pain during sexual activity, the loose design and thick material of FCs, and difficulties in placing FCs were the major obstacles to FC use among MSM. The elements referring to the forehead exhibited varied in importance among "1,", "0," and "0.5" participants. Regarding the willingness to use the FC in the future anal intercourse, 61.54% of participants expressed a positive inclination, 23.08% were uncertain, and 15.38% stated that they would not. "A better sense of security during anal sex" was the main factor affecting willingness among "0" participants and "the sexual pleasure that the FC brought" among "1" participants. Improving the design and technology of FCs and increasing the frequency of use and practice might improve the use skills, which will favor the willingness to use FCs among the MSM population. Conclusion: FCs received positive user feedback from study participants, but distinctions were found in individuals in different sexual roles. Large-scale quantitative studies are needed to evaluate the clinical safety of the FC and its effectiveness in preventing the transmission of STDs during anal intercourse.
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Condones Femeninos , Minorías Sexuales y de Género , Femenino , Humanos , Masculino , China , Homosexualidad Masculina , Dolor , Conducta Sexual , Investigación CualitativaRESUMEN
Emerging contaminants (ECs) in aquatic environments have attracted attention due to their wide distribution and potential ecotoxicities. Sewage treatment plants (STPs) are proven to be the major source of ECs in the aquatic environment, while there remains insufficient understanding of the removal and risk assessment of ECs in STPs. Here, we clarified the degradation and risk impact of 13 ECs in two aquatic product processing sewage treatment plants (APPSTPs) along the southeast coast of China. The concentrations of ECs followed the order: endocrine-disrupting chemicals (1877.85-15,398.02 ng/L in influent, 3.37-44.47 ng/L in effluent) > > sulfonamide antibiotics (SAs, 75.14-906.19 ng/L in influent, 1.14-15.33 ng/L in effluent) > pharmaceutical and personal care products (PPCPs, 44.47-589.93 ng/L in influent, 2.54-34.16 ng/L in effluent) ≈ fluoroquinolone antibiotic (54.76-434.83 ng/L in influent, 10.75-32.82 ng/L in effluent) > other antibiotics (16.21-51.96 ng/L in influent, 0.68-6.17 ng/L in effluent). Moreover, the concentrations of PPCPs (decreased by 55.33-87.65% in peak fishing season) and antibiotics (increased by 44.99% in peak fishing season) were affected by fishing activities. In particular, the sequencing batch reactor (SBR) process had a better removal effect than the anaerobic-anoxic-oxic (A2/O) process on the treatment of some contaminants (e.g., norfloxacin and nonylphenol). Risk evaluations of ECs demonstrated that nonylphenol and SAs were at high- and low-risk states, respectively. Overall, our results provide important information for the degradation treatment of ECs, which is essential for pollutant management policy formulation.
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Aguas del Alcantarillado , Contaminantes Químicos del Agua , Aguas del Alcantarillado/análisis , Eliminación de Residuos Líquidos , Contaminantes Químicos del Agua/análisis , Antibacterianos/análisis , Medición de Riesgo , Monitoreo del AmbienteRESUMEN
Carbon-supported Pd-based clusters are one of the most promising anodic catalysts for ethanol oxidation reaction (EOR) due to their encouraging activity and practical applications. However, unclear growth mechanism of Pd-based clusters on the carbon-based materials has hindered their extensive applications. Herein, we first introduce multi-void spherical PdBi cluster/carbon cloth (PdBi/CC) composites by an electrodeposition routine. The growth mechanism of PdBi clusters on the CC supports has been systemically investigated by evaluating the selected samples and tuning their compositions, which involve the big difference in standard redox potential between Pd2+/Pd and Bi3+/Bi and easy adsorption of Bi3+ on the surface of Pd-rich seeds. Benefitting from the ensembles of many nanocrystal subunits, multi-void spherical PdBi clusters can present collective properties and novel functionalities. In addition, the outstanding characteristics of CC supports enable PdBi clusters with stable nanostructures. Thanks to the unique structure, Pd20Bi/CC catalysts manifest higher EOR activity and better stability compared to Pd/CC. Systematic characterizations and a series of CO poisoning tests further confirm that the dramatically enhanced EOR activity and stability can be attributed to the incorporation of Bi species and the strong coupling of the structure between PdBi clusters and CC supports.
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BACKGROUND: Neuron-specific enolase (NSE), which is a highly specific marker for neurons, could be a predictor for prognosis in patients with symptomatic intracranial hemorrhage (sICH) with acute ischemic stroke who are receiving endovascular treatment (EVT). This study aimed to investigate the relationship between NSE and sICH in patients with acute anterior circulation stroke undergoing EVT. METHODS: A total of 215 consecutive patients with acute stroke treated with EVT were included. Patients with stroke and acute anterior circulation occlusion, receiving EVT treated at our hospital, were enrolled between January 2017 and August 2021. NSE level was measured on arrival at the neurology intensive care unit after EVT. The patients were divided into 2 groups according to whether sICH was present. Univariate and multivariate analyses were performed. NSE level was also incorporated into the TAG score (modified Thrombolysis in Cerebral Infarction score, Alberta Stroke Program Early CT Score, and glucose level), which was developed as a scoring system to predict sICH, and the prediction capability was compared with the TAG score alone. Causal inference was performed using the package DoWhy in Python to evaluate the causal relationship between NSE and sICH. RESULTS: The area under the curve (AUC) value of NSE showed moderate accuracy, with an AUC value of 0.729 (95% confidence interval, 0.655-0.795; P < 0.001). The NSE cutoff value was set at 23.88 ng/mL. When the NSE level ≥23.88 ng/mL, the sensitivity was 58.33% and the specificity was 78.72% (P < 0.001). The AUC for the TAG + NSE score was 0.801 compared with an AUC of 0.632 for the TAG score (Z = 2.034; P = 0.042). A causal inference model using the DoWhy library shows a proportional relationship between NSE and the diagnosis of sICH. CONCLUSIONS: This study is the first to show that increased NSE level is an independent predictor of sICH in patients with acute anterior circulation stroke who are undergoing endovascular treatment.
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Isquemia Encefálica , Procedimientos Endovasculares , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular Isquémico/complicaciones , Accidente Cerebrovascular Isquémico/diagnóstico por imagen , Accidente Cerebrovascular Isquémico/cirugía , Isquemia Encefálica/complicaciones , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/cirugía , Resultado del Tratamiento , Hemorragias Intracraneales/etiología , Hemorragias Intracraneales/complicaciones , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/cirugía , Trombectomía/efectos adversos , Fosfopiruvato Hidratasa , Procedimientos Endovasculares/efectos adversosRESUMEN
OBJECTIVES: To compare the prediction effects of six models based on machine learning theories, which can provide a methodological reference for predicting the risk of type 2 diabetes mellitus (T2DM). SETTING AND PARTICIPANTS: This study was based on the monitoring data of chronic disease risk factors in Dongguan residents from 2016 to 2018. The multistage cluster random sampling method was adopted at each monitoring site, and 4157 people were finally selected. In the initial population, we excluded individuals with more than 20% missing data and eventually included 4106 subjects. DESIGN: K nearest neighbour algorithm and synthetic minority oversampling technique were used to process the data. Single factor analysis was used for preliminary selection of variables. The 10-fold cross-validation was used to optimise the parameters of some models. The accuracy, precision, recall and area under receiver operating characteristic curve (AUC) were used to evaluate the prediction effect of models, and Delong test was used to analyse the differences of AUC values of each model. RESULTS: After balancing data, the sample size increased to 8013, of which 4023 are patients with T2DM and 3990 in control group. The comparison results of the six models showed that back propagation neural network model has the best prediction effect with 93.7% accuracy, 94.6% accuracy, 92.8% recall and the AUC value of 0.977, followed by logistic model, support vector machine model, CART decision tree model and C4.5 decision tree model. Deep neural network has the worst prediction performance, with 84.5% accuracy, 86.1% precision, 82.9% recall and the AUC value of 0.845. CONCLUSIONS: In this study, six types of risk prediction models for T2DM were constructed, and the predictive effects of these models were compared based on various indicators. The results showed that back propagation neural network based on the selected data set had the best prediction effect.
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Diabetes Mellitus Tipo 2 , Humanos , Estudios Transversales , Diabetes Mellitus Tipo 2/epidemiología , Algoritmos , Análisis por Conglomerados , Aprendizaje AutomáticoRESUMEN
Ulcerative colitis (UC) is an inflammatory bowel disease (IBD), and its pathogenesis is related to intestinal mucosal barrier damage and gut microbiota imbalance. Protopine (PRO), an isoquinoline alkaloid, is one of the main anti-inflammatory ingredients of traditional Chinese medicine Macleaya cordata(Willd.) R. Br. This study investigated the effects of PRO on the intestinal mucosal barrier and gut microbiota in dextran sodium sulfate (DSS)-induced colitis mice. C57BL/6J mice were treated with 3% DSS in drinking water to induce acute colitis, while PRO was administered orally once daily for 7 days. The results showed that PRO administration significantly alleviated the symptoms of DSS-induced colitis in mice and inhibited the expression of inflammation-related genes. In addition, PRO restored the integrity of the intestinal barrier in colitis mice by restoring colonic mucin secretion and promoting the expression of tight junction proteins. Furthermore, PRO alleviated the DSS-induced gut microbiota dysbiosis by decreasing the abundance of Proteobacteria, Escherichia-Shigella and Enterococcus, as well as enhancing the abundance of beneficial bacteria, such as Firmicutes and Akkermansia. These findings suggested that PRO effectively alleviated DSS-induced ulcerative colitis by suppressing the expression of inflammation-related genes, maintaining the intestinal mucosal barrier and regulating the intestinal microbiota.
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Colitis Ulcerosa , Colitis , Microbioma Gastrointestinal , Animales , Ratones , Ratones Endogámicos C57BL , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/tratamiento farmacológico , Dextranos , Inflamación , Colon , Sulfato de Dextran/efectos adversos , Modelos Animales de EnfermedadRESUMEN
With the increasingly strict discharge requirements, it is urgent for wastewater treatment plants (WWTPs) to find an efficient and feasible technology for advanced treatment. A three-dimensional (3D) electrode system was used to treat the real biochemical effluent of a WWTP collecting industrial and domestic wastewater in the present study. The 3D electrode system had the best performance at a current density of 2 mA/cm2 and an electrode distance of 3 cm. The kinetic analysis showed that the organic pollutant degradation conformed to pseudo-first-order kinetics. The COD removal of the 3D electrode system was more than twice that of the two-dimensional (2D) electrode system, and the energy consumption was 46.56% less than that of the 2D electrode system. By measuring the adsorption capacity and the electrocatalytic ability of the system to produce strong oxidizing species, it was demonstrated that granular activated carbon (GAC) had the synergy of adsorption and electrochemical oxidation, and ·OH playing the dominant role in oxidizing pollutants. At the same time, the organic contaminants adsorbed on GAC could be degraded. Finally, the adsorption-electrochemical oxidation mechanism was proposed. The above results highlighted that the 3D electrode system was a promising alternative method in the application of advanced treatment for WWTPs.
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Contaminantes Ambientales , Contaminantes Químicos del Agua , Purificación del Agua , Contaminantes Químicos del Agua/análisis , Cinética , Aguas Residuales , Carbón Orgánico , Purificación del Agua/métodos , Electrodos , Contaminantes Ambientales/análisis , Eliminación de Residuos Líquidos/métodosRESUMEN
Allocryptopine (ALL) is an isoquinoline alkaloid extracted from Macleaya cordata(Willd). R. Br., which has been claimed to have anti-inflammatory and neuroprotection properties. However, the mechanism by which ALL ameliorates inflammatory bowel disease (IBD) remains unclear. Here, we used network pharmacology and quantitative proteomic approaches to investigate the effect of ALL on IBD pathogenesis. Network pharmacology predicted potential targets and signaling pathways of ALL's anti-IBD effects. As predicted by network pharmacology, gene ontology (GO) analysis, in terms of the proteomic results, showed that the immune response in mucosa and antimicrobial humoral response were enriched. Further study revealed that the ALL-related pathways were the chemokine signaling pathway and apoptosis in the Kyoto Encyclopedia of Genes and Genomes (KEGG). In addition, we identified AKT1 as a hub for the critical pathways through protein-protein interaction (PPI) network analysis. Similar to mesalazine (MES), Western blot verified that ALL downregulated upstream chemokine CX3CL1 and GNB5 content to reduce phosphorylation of AKT and NF-κB, as well as the degree of apoptosis, to improve inflammatory response in the colon. Our research may shed light on the mechanism by which ALL inhibits the CX3CL1/GNB5/AKT2/NF-κB/apoptosis pathway and improves the intestinal barrier to reduce colitis response and act on the CX3CL1-CX3CR1 axis to achieve neuroprotection.
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BACKGROUND: Human umbilical cord-derived mesenchymal stem cell (hUC-MSC) engraftment is a promising therapy for acute ischemic stroke (AIS). However, the harsh ischemic microenvironment limits the therapeutic efficacy of hUC-MSC therapy. Curcumin is an anti-inflammatory agent that could improve inflammatory microenvironment. However, whether it enhances the neuroprotective efficacy of hUC-MSC transplantation is still unknown. In the present study, we investigated the therapeutic efficacy and the possible mechanism of combined curcumin and hUC-MSC treatment in AIS. METHODS: Middle cerebral artery occlusion (MCAO) mice and oxygen glucose deprivation (OGD) microglia were administrated hUC-MSCs with or without curcumin. Neurological deficits assessment, brain water content and TTC were used to assess the therapeutic effects of combined treatment. To elucidate the mechanism, MCAO mice and OGD microglia were treated with AKT inhibitor MK2206, GSK3ß activator sodium nitroprusside (SNP), GSK3ß inhibitor TDZD-8 and Nrf2 gene knockout were used. Immunofluorescence, flow cytometric analysis, WB and RT-PCR were used to evaluate the microglia polarization and the expression of typical oxidative mediators, inflammatory cytokines and the AKT/GSK-3ß/ß-TrCP/Nrf2 pathway protein. RESULTS: Compared with the solo hUC-MSC-grafted or curcumin groups, combined curcumin-hUC-MSC therapy significantly improved the functional performance outcomes, diminished the infarct volumes and the cerebral edema. The combined treatment promoted anti-inflammatory microglia polarization via Nrf2 pathway and decreased the expression of ROS, oxidative mediators and pro-inflammatory cytokines, while elevating the expression of the anti-inflammatory cytokines. Nrf2 knockout abolished the antioxidant stress and anti-inflammation effects mediated with combined treatment. Moreover, the combined treatment enhanced the phosphorylation of AKT and GSK3ß, inhibited the ß-TrCP nucleus translocation, accompanied with Nrf2 activation in the nucleus. AKT inhibitor MK2206 activated GSK3ß and ß-TrCP and suppressed Nrf2 phosphorylation in nucleus, whereas MK2206 with the GSK3ß inhibitor TDZD-8 reversed these phenomena. Furthermore, combined treatment followed by GSK3ß inhibition with TDZD-8 restricted ß-TrCP nucleus accumulation, which facilitated Nrf2 expression. CONCLUSIONS: We have demonstrated that combined curcumin-hUC-MSC therapy exerts anti-inflammation and antioxidant stress efficacy mediated by anti-inflammatory microglia polarization via AKT/GSK-3ß/ß-TrCP/Nrf2 axis and an improved neurological function after AIS.
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Curcumina , Accidente Cerebrovascular Isquémico , Trasplante de Células Madre Mesenquimatosas , Humanos , Ratones , Animales , Glucógeno Sintasa Quinasa 3 beta , Proteínas Proto-Oncogénicas c-akt , Proteínas con Repetición de beta-Transducina , Factor 2 Relacionado con NF-E2 , Antioxidantes , Infarto de la Arteria Cerebral Media , Citocinas , Cordón Umbilical , Antiinflamatorios/farmacologíaRESUMEN
BACKGROUND: Malignant cerebral edema (MCE) is a common and feared complication after endovascular thrombectomy (EVT) in acute ischemic stroke (AIS). This study aimed to establish a nomogram to predict MCE in anterior circulation large vessel occlusion stroke (LVOS) patients receiving EVT in order to guide the postoperative medical care in the acute phase. METHODS: In this retrospective cohort study, 381 patients with anterior circulation LVOS receiving EVT were screened from 636 hospitalized patients with LVOS at 2 stroke medical centers. Clinical baseline data and imaging data were collected within 2-5 days of admission to the hospital. The patients were divided into 2 groups based on whether MCE occurred after EVT. Multivariate logistic regression analysis was used to evaluate the independent risk factors for MCE and to establish a nomogram. RESULTS: Sixty-six patients out of 381 (17.32%) developed MCE. The independent risk factors for MCE included admission National Institutes of Health Stroke Scale (NIHSS) ≥16 (odds ratio [OR] 1.851; 95% CI 1.029-3.329; P = 0.038), ASPECT score (OR 0.621; 95% CI 0.519-0.744; P < 0.001), right hemisphere (OR 1.636; 95% CI 0.941-2.843; P = 0.079), collateral circulation (OR 0.155; 95% CI 0.074-0.324; P < 0.001), recanalization (OR 0.223; 95% CI 0.109-0.457; P < 0.001), hematocrit (OR, 0.937; 95% CI: 0.892-0.985; P =0.010), and glucose (OR 1.118; 95% CI 1.023-1.223; P = 0.036), which were adopted as parameters of the nomogram. The receiver operating characteristic curve analysis showed that the area under the curve of the nomogram in predicting MCE was 0.901(95% CI 0.848-0.940; P < 0.001). The Hosmer-Lemeshow test results were not significant (P = 0.685), demonstrating a good calibration of the nomogram. CONCLUSIONS: The novel nomogram composed of admission NIHSS, ASPECT scores, right hemisphere, collateral circulation, recanalization, hematocrit, and serum glucose provide a potential predictor for MCE in patients with AIS after EVT.
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Arteriopatías Oclusivas , Edema Encefálico , Isquemia Encefálica , Procedimientos Endovasculares , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular Isquémico/etiología , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/cirugía , Isquemia Encefálica/complicaciones , Nomogramas , Estudios Retrospectivos , Edema Encefálico/etiología , Edema Encefálico/complicaciones , Accidente Cerebrovascular/etiología , Trombectomía/efectos adversos , Trombectomía/métodos , Arteriopatías Oclusivas/complicaciones , Glucosa , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/métodos , Resultado del TratamientoRESUMEN
This study fabricated a novel excipient emulsion by adding dark tea polysaccharides to improve the bioaccessibility of lycopene from tomatoes. Results indicated that addition of tea polysaccharides greatly increased the antioxidant activity of excipient emulsions. Additionally, tea polysaccharides markedly improved the physical stability of excipient emulsion when being mixed with tomato puree and passing through a simulated gastrointestinal tract, contributing to an increase in electrostatic and steric repulsion between the droplets. Besides, certain amount of tea polysaccharides (0.05 - 0.2 wt%) could increase the rate and extent of lipid digestion in tomato-emulsion mixtures. Finally, lycopene bioaccessibility was significantly increased (from 16.95 % to 26.21 %) when 0.1 wt% tea polysaccharides were included, which was mainly ascribed to the ability of tea polysaccharides to increase lipid digestion and reduce carotenoid oxidation within the gastrointestinal tract. These results suggest that well-designed excipient emulsions may increase carotenoids bioavailability in the complex food matrices.
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Solanum lycopersicum , Licopeno , Emulsiones , Excipientes , Carotenoides , Suplementos Dietéticos/análisis , Lípidos , TéRESUMEN
The research on targeted therapy of hypopharyngeal cancer is very scarce. The discovery of new targeted driver genes will promote the progress of hypopharyngeal cancer therapy to a great extent. In our research, whole-exome sequencing in 10 patients with hypopharyngeal cancer was performed to identify single nucleotide variations (SNVs) and insertions and deletions (INDELs). American College of Medical Genetics and Genomics (ACMG) guidelines were used to evaluate the pathogenicity of the selected variants. 8113 mutation sites in 5326 genes were identified after strict screening. We identified 72 pathogenic mutations in 53 genes according to the ACMG guidelines. Gene Ontology (GO) annotation and KEGG enrichment analysis show the effect of these genes on cancer. Protein-protein interaction (PPI) was analyzed by string online software. The validation results of the ualcan database showed that 22 of the 53 genes may be related to the poor prognosis of patients with hypopharyngeal cancer. RBM20 has the most significant correlation with hypopharyngeal cancer, and it is likely to be the driver gene of hypopharyngeal cancer. In conclusion, we found possible therapeutic targets for hypopharyngeal cancer, especially RBM20 and KMT2C. Our study provides a basis for the pathogenesis and targeted therapy of hypopharyngeal cancer.
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Neoplasias Hipofaríngeas , Humanos , Secuenciación del Exoma , Neoplasias Hipofaríngeas/genética , Detección Precoz del Cáncer , Mutación , GenómicaRESUMEN
Influences of conventional thermal and innovative non-thermal extraction methods on the physicochemical characteristics and properties of pectic polysaccharides from Choerospondias axillaris peels were investigated. Results showed that ultrasound-assisted extracted polysaccharides (UP) had a heterogeneous nature with lower molecular weight (127.7 kDa) and lower neutral sugar content (35.1%) but higher contents of protein (4.8%) and phenolic compounds (5.1%) than those of polysaccharides extracted by hot water (HP). Additionally, the monosaccharide composition results showed that glucose (77.8%) was the most abundant monosaccharide in HP, while arabinose (67.1%) was the most abundant monosaccharide in UP. The ultrasound significantly induced the degradation of polysaccharide chains but reduced the thermal degradation of phenolics. Finally, we found that UP had higher apparent viscosity, interfacial, emulsifying and antioxidant activity but lower α-glucosidase inhibition activity than those of HP. The results indicated that we could obtain polysaccharides with different functional and biological properties by using different extraction methods.
Asunto(s)
Anacardiaceae , Pectinas , Pectinas/química , Antioxidantes/química , alfa-Glucosidasas/metabolismo , Arabinosa , Anacardiaceae/química , Polisacáridos/química , Monosacáridos , Agua/química , Fenoles , GlucosaRESUMEN
BACKGROUND: Chronic inflammation of adipose tissue may be one of the key factors contributing to the development of insulin resistance in T2DM adipose tissue. Transient receptor potential vanilloid type 4 (TRPV4) can be involved in a variety of cellular inflammatory responses. In this study, we evaluated the role of TRPV4 channelin in the T2DM adipose tissue inflammatory pathway. METHODS: Based on the gene expression profiling data of the public database, bioinformatics methods were used to screen the target gene population of the TRPV4 channel protein involved in the regulation of T2DM fat cells. A mature adipocyte model was constructed to verify the expression level of target genes and to evaluate the regulatory effect of TRPV4 channel inhibition on target genes of inflammation-related pathways. RESULTS: In shTRPV4 adipocytes, 144 genes with downregulation expression were screened, a PPI network was constructed and a core module containing 15 genes was screened out, and the core genes were mainly enriched in the Toll-like receptor signaling pathway through enrichment analysis. Constructing a mature adipocyte model found that the TRPV4 inhibitor HC067047 inhibited the effect of upregulation of the expression level of the relevant gene in the signaling pathway. CONCLUSIONS: Our findings suggest that the expression of highly expressed pro-inflammatory cytokines and chemokines in T2DM adipose tissue decreases after inhibiting the expression of TRPV4 in adipocytes, suggesting that TRPV4 may become a potential drug target for the treatment of T2DM.