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1.
Front Immunol ; 12: 725063, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34630399

RESUMO

Leukocytes offer a critical layer of protection to the host following skin infections. Delineating the kinetics of cutaneous leukocyte recruitment as well as their anti-microbial and regulatory profiles is challenging since it requires the isolation of adequate cell numbers and maintenance of their functional properties. Herein, we took advantage of a modified procedure to gain insights into the contributions of fish phagocytes through induction and resolution phases of acute cutaneous inflammation in goldfish (Carassius auratus). Our data shows early upregulation of pro-inflammatory cytokines and chemokines, which was paired with neutrophil-dominant leukocyte migration of neutrophils from circulation to the injury site. Recruited neutrophils were associated with high levels of reactive oxygen species (ROS). Following pathogen elimination, a reduction in ROS levels and pro-inflammatory cytokines expression preceded the resolution of inflammation. These results provide a better understanding of the cutaneous immune responses in fish. Moreover, the increased viability and functionality of isolated skin leukocytes opens the door to better understand a range of additional skin diseases.

2.
Technol Cancer Res Treat ; 20: 15330338211045510, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34617858

RESUMO

This study aimed to investigate the expression and cellular function of the centromeric family of proteins (CENPs), especially centromere protein I (CENP-I), in gastric cancer (GC) and identified its clinical significance and cellular functions. CENP-I expression in GC was studied by cDNA microarray, quantitative real-time PCR (qRT-PCR), and immunohistochemistry (IHC), and using datasets from The Cancer Genome Atlas (TCGA), UALCAN, and Gene Expression Omnibus (GEO) databases. Microarray and bioinformatic analyses identified upregulated CENP-A/E/F/H/I/K/P/W and HJURP in stomach adenocarcinoma (STAD), but not in signet ring cell carcinoma (SRCC). Significantly higher CENP-I mRNA expression was also confirmed in 40 pairs of GC tissues than in paired normal gastric tissues by qRT-PCR (P<.001). IHC showed that elevated CENP-I expression was associated with higher tumor stage, lymph node invasion, increased HER2-positive rate (36.7% vs 10.0%), and intestinal Lauren classification in 69 GC samples compared to paired paracancerous normal tissues. The survival of the high-CENP-I group members was poor compared with that of the low-CENP-I group (P = .0011). Cox univariate regression analysis identified tumor size (P = .008), HER2 status (P = .027), and CENP-I expression (P = .049) were independent prognostic factors of GC. The cellular function of CENP-I was studied in MKN45 and MKN28 GC cell lines in vitro. Cell proliferation, migration, and apoptosis were determined using CCK-8, transwell assay, TUNEL assay, and flow cytometry. Our results showed that CENP-I promoted GC cell proliferation, inhibited apoptosis, facilitated cell migration, and induced epithelial-mesenchymal transition (EMT), possibly by activating the AKT pathway. CENP-I expression was correlated with genetic signatures of the proliferative subtype of GC, characterized by intestinal Lauren classification, HER2 amplification, and TP53 mutation. In conclusion, this study revealed an elevated CENP-I expression in GC, which was associated with malignant features and poor prognosis of GC patients, and identified its function in modulating cell proliferation, apoptosis, and migration.

3.
Nanomaterials (Basel) ; 11(10)2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34685095

RESUMO

As a widely applied nanomaterial, silver nanomaterials (AgNMs) have increased public concern about their potential adverse biological effects. However, there are few related researches on the long-term toxicity, especially on the reversibility of AgNMs in vivo. In the current study, this issue was tackled by exploring liver damage after an intravenous injection of silver nanorods with golden cores (Au@AgNRs) and its potential recovery in a relatively long term (8 w). After the administration of Au@AgNRs into rats, Ag was found to be rapidly cleared from blood within 10 min and mainly accumulated in liver as well as spleen until 8 w. All detected parameters almost displayed a two-stage response to Au@AgNRs administration, including biological markers, histological changes and metabolic variations. For the short-term (2 w) responses, some toxicological parameters (hematological changes, cytokines, liver damages etc.) significantly changed compared to control and AuNRs group. However, after a 6-week recovery, all abovementioned changes mostly returned to the normal levels in the Au@AgNRs group. These indicated that after a lengthy period, acute bioeffects elicited by AgNMs could be followed by the adaptive recovery, which will provide a novel and valuable toxicity mechanism of AgNMs for potential biomedical applications of AgNMs.

4.
Front Vet Sci ; 8: 750895, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34646877

RESUMO

Antibiotic resistance is an increasingly prevalent problem worldwide. Probiotics are live microorganisms that provide health benefits to human beings and animals and also antimicrobial activity against pathogens and might be an antibiotic alternative. The gastrointestinal tract of animals can be a suitable source of finding novel antimicrobial agents, where the vast majority of gut microbes inhabit and a plurality of antimicrobial producers exhibit either a wide or narrow spectrum. Animals that live in Northwest China might possess a special commensal community in the gut. Therefore, the purpose of this study was to assess the effects of three probiotic strains (including Lactobacillus salivarius ZLP-4b from swine, Lactobacillus plantarum FBL-3a from beef cattle, and Bacillus velezensis JT3-1 from yak), which were isolated from livestock in this area, on the overall growth performance, immune function, and gut microbiota of mice. The results showed that the L. salivarius ZLP-4b group not only improved the growth performance but also amended the intestinal mucosa morphology of mice. Furthermore, the supplementation of L. plantarum FBL-3a and L. salivarius ZLP-4b strains significantly increased the content of anti-inflammatory cytokines IL-4 and IL-10 but decreased the pro-inflammatory factor IL-17A. The levels of pro-inflammatory factors IL-6, IL-17A, and TNF-α were also decreased by the B. velezensis JT3-1 group pretreatment. The 16S rDNA sequence results showed that the probiotic administration could increase the proportion of Firmicutes/Bacteroidetes intestinal microbes in mice. Furthermore, the relative abundance of Lactobacillus was boosted in the JT3-1- and ZLP-4b-treated groups, and that of opportunistic pathogens (including Proteobacteria and Spirochaetes) was diminished in all treated groups compared with the control group. In conclusion, B. velezensis JT3-1 and L. salivarius ZLP-4b supplementation enhanced the overall performance, intestinal epithelial mucosal integrity, and immune-related cytokines and regulated the intestinal microbiota in mice.

5.
Int J Clin Pract ; : e14877, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34525256

RESUMO

BACKGROUND: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are widely used to treat patients with EGFR-mutated non-small cell lung cancers (NSCLCs). The association between the clinical outcomes of patients on first-line EGFR-TKIs and the efficacy of osimertinib as second-line treatment has not been previously assessed. This is our topic here. PATIENTS AND METHODS: We retrospectively analysed 67 patients with EGFR mutations on osimertinib after treatment with first-generation EGFR-TKIs. We evaluated patient characteristics, the EGFR T790M allele frequency in plasma samples and clinical outcomes. RESULTS: When osimertinib was given as second-line treatment, the median progression-free survival (PFS) was 6.0 months, and the response rate and disease control rate were 32.8% and 91.0%, respectively. Correlation analysis showed that the female sex and isolated (not multiple) progression on first-line EGFR-TKIs were correlated with a superior response to osimertinib. Kaplan-Meier analysis showed that patients exhibiting a partial response, isolated progression, and longer PFS on first-line EGFR-TKIs experienced prolonged PFS on osimertinib. Univariate analysis indicated that the treatment response, PFS and progression when on first-line EGFR-TKIs affected the PFS on osimertinib. Multivariate analysis showed that progression when on first-line EGFR-TKIs was independently prognostic of a response to osimertinib. The median PFS of patients with isolated progressive disease PD alone who were receiving brain radiotherapy was significantly longer than that of patients with isolated progressive disease alone who did not receive brain radiotherapy as well as patients exhibiting multiple progression. A low frequency of the EGFR T790M allele in plasma tended to predict an inferior efficacy of osimertinib and shorter PFS. CONCLUSION: We found that patients who benefited from first-line EGFR-TKIs may experience prolonged PFS and a higher response rate when subsequently given osimertinib. A low plasma frequency of the EGFR T790M allele may predict poor osimertinib efficacy and shorter PFS.

6.
Plant J ; 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34583419

RESUMO

Plants sense various pathogens and activate immunity responses through receptor-like kinases (RLKs). Cysteine-rich receptor-like kinases (CRKs) are involved in massive transduction pathways upon perception of a pathogen. However, the roles of CRKs in response to stripe rust are unclear. In the present study, we identified a CRK gene (designated TaCRK10) from wheat variety Xiaoyan 6 (XY6) that harbors high-temperature seedling-plant (HTSP) resistance to stripe rust caused by fungal pathogen Puccinia striiformis f. sp. tritici (Pst). The expression level of TaCRK10 was induced by Pst inoculation and high temperature treatment. Knockdown of TaCRK10 by virus-induced gene silencing resulted in attenuated wheat HTSP resistance to Pst, whereas there is no effect on Pst development and host responses under normal temperatures. Notably, overexpression of TaCRK10 in susceptible variety Fielder provided resistance only under normal temperatures at 14 days with reactive oxygen species accumulation and defense-related gene expression of the salicylic acid pathway. Moreover, TaCRK10 physically interacted with and phosphorylated a histone variant TaH2A.1, which belongs to the H2A.W group. Silencing of TaH2A.1 suppressed wheat resistance to Pst, indicating that TaH2A.1 plays a positive role in wheat resistance to Pst. Thus, TaCRK10 serves as an important sensor of Pst infection and high temperatures, and it activates wheat resistance to Pst through regulating nuclear processes. This knowledge helps elucidate the molecular mechanism of wheat HTSP resistance to Pst and promotes efforts in developing wheat varieties with resistance to stripe rust.

7.
Chemosphere ; 287(Pt 3): 132324, 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34563777

RESUMO

Biological assays are useful in water quality evaluation by providing the overall toxicity of chemical mixtures in environmental waters. However, it is impossible to elucidate the source of toxicity and some lethal combination of pollutants simply using biological assays. As facile and cost-effective methods, computation model-based toxicity assessments are complementary technologies. Herein, we predicted the human health risk of binary pollutant mixtures (i.e., binary combinations of As(III), Cd(II), Cr(VI), Pb(II) and F(I)) in water using in vitro biological assays and deep learning methods. By employing a human cell panel containing human stomach, colon, liver, and kidney cell lines, we assessed the human health risk mimicking cellular responses after oral exposures of environmental water containing pollutants. Based on the experimental cytotoxicity data in pure water, multi-task deep learning was applied to predict cellular response of binary pollutant mixtures in environmental water. Using additive descriptors and single pollutant toxicity data in pure water, the established deep learning model could predict the toxicity of most binary mixtures in environmental water, with coefficient of determination (R2) > 0.65 and root mean squared error (RMSE) < 0.22. Further combining the experimental data on synergistic and antagonistic effects of pollutant mixtures, deep learning helped improve the predictive ability of the model (R2 > 0.74 and RMSE <0.17). Moreover, predictive models allowed us identify a number of toxicity source-related physiochemical properties. This study illustrates the combination of experimental findings and deep learning methods in the water quality evaluation.

8.
Arch Microbiol ; 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34581832

RESUMO

In this study, we screened bacterial strains to identify specific probiotics to treat pig diarrhea caused by Escherichia coli or Salmonella. The potential probiotics were assayed for their survival in gastrointestinal solution, their antimicrobial activity, cell-surface properties, adhesion to Caco-2 cells, and inhibition of pathogen adhesion. Nine out of the 20 strains tested showed high tolerance of a simulated gastrointestinal environment and six strains exerted antagonistic effects against enterohemorrhagic E. coli (EHEC) O157:H7 and Salmonella Typhimurium MQ. Lactobacillus johnsonii pDX1e exhibited a higher potent antibacterial activity. Four strains (pDX1a, pDX1e, pDX3a, and pDX5a) displayed auto-aggregation, hydrophobicity, and adhesion to Caco-2 cells similar to those of the reference strain Lacticaseibacillus rhamnosus GG (LGG). Enterococcus durans pDX5a showed the highest adhesion capacity (13.86%), followed by the reference strain LGG (11.20%). All the tested strains competitively suppressed the attachment of pathogens to Caco-2 cells (by 30.73-55.18%); L. johnsonii pDX1e and Ent. durans pDX5a significantly inhibited the adhesion of pathogens by substitution and exclusion, respectively. Therefore, pDX1e and pDX5a were selected as probiotic strains for further investigation and application.

9.
Sci Rep ; 11(1): 19018, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34561467

RESUMO

According to the statistics of 160 typical fire and explosion accidents in oil storage areas at home and abroad nearly 50 years, 122 of them occurred the secondary accidents in the emergency responses. Based on 122 accident cases, 21 causal factors leading to secondary accidents are summarized. In order to quantify the influencing degree of these causal factors on the accident consequences, a multiple linear regression model was established between them. In the modeling process, these factors are decomposed into the criterion layer, variable layer, and bottom layer. The improved analytic hierarchy process (IAHP) was used to establish the relationship between the bottom factors and variable factors, and the regression analysis method was used to establish the relational model between variable layer and criterion layer. For 122 cases of the secondary accidents, this study took the year as a statistical dimension, and obtained 40 groups of sample data. The first 34 groups of sample data were used to build the causal factors model, and the last 6 groups of sample data were tested the generalization ability of the model by using the established regression model combined with grey prediction model. The results show that the prediction ability of the established model was better than that of the grey prediction model alone. Moreover, the relative contribution and change trend of the causal factors were evaluated using the mutation progression method, and corresponding preventive countermeasures were proposed. It was found that human professional skills, knowledge and literacy, environmental issues, and firefighting facilities are the main influencing factors that lead to the secondary accidents. These three kinds of factors show a gradual improvement trend, and the existing prevention measures should be maintained and further improved. The problem of inherent objects or equipment factors has not been effectively improved and has a worsening trend, which is the focus of prevention in the future, and the prevention and control efforts need to be moderately increased. The research results have important guiding significance for understanding the quantitative influences of causal factors on the accident consequences, improving emergency response capabilities, reducing accident losses, and avoiding secondary accidents.

10.
Nanoscale ; 13(34): 14417-14425, 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34473184

RESUMO

The recurrence and metastasis of tumor after surgery is the main cause of death for patients with breast cancer. Systemic chemotherapy suffered from low delivery efficiency to tumors and the side effects of chemo drugs. Localized chemotherapy using drug-containing implants is an alternative, while the reconstruction of breast tissue is generally considered after chemotherapy, resulting in a second surgery for patients. Here, we describe a strategy using implantable drug-containing polymeric scaffolds to deliver chemo drugs directly to the post-resection site, and simultaneously provide mechanical support and regenerative niche for breast tissue reconstruction. When doxorubicin was loaded in mesoporous silica nanoparticles and subsequently incorporated into polycaprolactone scaffolds (DMSN@PCL), a 9-week sustained drug release was achieved post implantation in mice. The local recurrence of residual tumor after surgery was significantly inhibited within 4 weeks in a post-surgical mouse model bearing xenograft MDA-MB-231 tumor. DMSN@PCL scaffolds exhibited good biocompatibility in mice during the treatment. We believe our strategy holds great promise as an adjuvant localized chemotherapy in clinics for combating post-resection breast cancer recurrence.


Assuntos
Antineoplásicos , Neoplasias da Mama , Nanopartículas , Animais , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Doxorrubicina/uso terapêutico , Feminino , Humanos , Camundongos , Poliésteres
11.
Front Psychol ; 12: 680614, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34484037

RESUMO

Objectives: The sudden outbreak of the novel coronavirus disease (COVID-19) plunged healthcare workers (HCWs) into warfare. This study aimed to determine the prevalence of burnout and the factors associated with it among frontline HCWs fighting COVID-19. Methods: A cross-sectional survey was conducted among frontline HCWs fighting against the COVID-19 in Wuhan, Harbin, and Shenzhen during the period from February 18 to March 4. Finally, HCWs were recruited using cluster sampling, 1,163 HCWs were included in the final analysis. Burnout was measured using a 22-item Maslach Burnout Inventory scale (MBI scale). Results: Of the participants, 48.6% suffered from burnout, and 21.8% showed a high degree of burnout. Doctors (b = 3.954, P = 0.011) and nurses (b = 3.067, P = 0.042) showed higher emotional exhaustion (EE) than administrators. Participants who worked continuously for more than 8 h a day (b = 3.392, P = 0.000), those who were unable to eat three regular daily meals (b = 2.225, P = 0.008), whose daily water intake was no more than 800 ml (b = 3.007, P = 0.000), who slept for no more than 6 h (b = 1.609, P = 0.036), and who were infected or had colleagues who were infected with COVID-19 (b = 4.182, P = 0.000) experienced much higher levels of EE, while those who could adhere to infection control procedures (b = -5.992, P = 0.000), who were satisfied with their hospital's infection control measures(b = -3.709, P = 0.001), and who could receive sufficient psychological crisis intervention (b = -1.588, P = 0.039) reported lower levels of EE. Conclusion: The study reveals that burnout is prevalent among frontline HCWs and that the known factors associated with burnout, such as workload, and the factors directly associated with COVID-19, such as having insufficient protection, can affect burnout symptoms in frontline HCWs. Synergized and comprehensive interventions should be targeted at reducing its occurrence among frontline HCWs fighting COVID-19.

12.
Reprod Sci ; 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34478121

RESUMO

CircRNA circFADS2 suppresses LPS-induced inflammation, which plays a critical role in endometritis. Our preliminary sequencing analysis revealed a positive correlation between circFADS2 and miR-643, which also play protective roles in LPS-induced inflammation. Therefore, this study was performed to explore the involvement of circFADS2 in endometritis with a focus on its interaction with miR-643. RT-qPCR was performed to analyze the levels circFADS2, mature miR-643, and premature miR-643 in plasma samples from endometritis patients (n = 66) and healthy controls (n = 66). Pearson's correlation coefficient was applied to analyze correlations between these genes. The effect of circFADS2 on miR-643 maturation was analyzed by measuring miR-643 and premature miR-643 levels in circFADS2-overexpressed human endometrial epithelial cell line HEnEpCs. The role of circFADS2 and miR-643 in HEnEpC apoptosis under LPS treatment was analyzed by cell apoptosis assay. CircFADS2 was downregulated in endometritis and was positively correlated with mature miR-643, but not premature miR-643. CircFADS2 overexpression in HEnEpCs increased the level of mature miR-643 but not premature miR-643. Cell apoptosis analysis showed that circFADS2 and miR-643 overexpression protected HEnEpCs from LPS-induced cell apoptosis, and miR-643 inhibition reduced the effect of circFADS2 overexpression. CircFADS2 is downregulated in endometritis, and it overexpression promotes miR-643 maturation in HEnEpCs to suppress cell apoptosis.

13.
Materials (Basel) ; 14(17)2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34500979

RESUMO

Ultrasonic energy is introduced into the Metal Inert Gas (MIG) welding arc and weld pool by superposition of an ultrasonic frequency current. In this study, the arc shape, arc energy, and ultrasonic energy that responded to ultrasonic excitation voltage and frequency is investigated. The comprehensive influence of arc and ultrasonic energy on weld formation, microstructure, and mechanical properties is further studied. The arc and ultrasonic energy are analyzed by using a high-speed camera and microphone, respectively. The results showed that the arc width increased, and the arc energy density decreased after the superposition of ultrasonic current. The arc height could be compressed under certain ultrasonic excitation parameters. The ultrasonic excitation voltage and frequency had a direct influence on the ultrasonic energy. The arc height, arc energy density, and ultrasonic energy together determined the weld width. Ultrasound could effectively refine the microstructure of the weld zone and fusion zone but had little effect on the heat-affected zone. Ultrasound improved the hardness of the joint by refining the grain and the second phase. The joint hardness was the highest when the ultrasonic excitation voltage was 100 V, and the frequency was 30 kHz.

14.
Front Public Health ; 9: 689809, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34422747

RESUMO

Background: In moving toward universal health coverage in China, it is crucial to identify which populations should be prioritized for which interventions rather than blindly increasing welfare packages or capital investments. We identify the characteristics of vulnerable groups from multiple perspectives through estimating catastrophic health expenditure (CHE) and recommend intervention priorities. Methods: Data were from National Health Service Survey conducted in 2003, 2008, and 2013. According to the recommendation of WHO, this study adopted 40% as the CHE threshold. A binary regression was used to identify the determinants of CHE occurrence; a probit model was used to obtain CHE standardized incidence under the characteristics of single and two dimensions in 2013. Results: The total incidence of CHE in 2013 was 13.9%, which shows a general trend of growth from 2003 to 2013. Families in western and central regions and rural areas were more at risk. Factors related to social demography show that households with a female or an unmarried head of household or with a low socioeconomic status were more likely to experience CHE. Households with older adults aged 60 and above had 1,524 times higher likelihood of experiencing CHE. Among the health insurance schemes, the participants covered by the New Rural Cooperative Medical Scheme had the highest risk compared with the participants of all basic health insurance schemes. Households with several members seeking outpatient, inpatient care or with non-communicable diseases were more likely to experience CHE. Households with members not seeing a doctor or hospitalized despite the need for it were more likely to experience CHE. Characteristics such as a household head with characteristics related to low socioeconomic status, having more than two hospitalized family members, ranked high. Meanwhile, the combination of having illiterate household heads and with being covered by other health insurance plans or by none ranked the first place. Cancer notably caused a relatively high medical expenditure among households with CHE. Conclusion: In China, considering the vulnerability of the population across different dimensions is conducive to the alleviation of high CHE. Furthermore, people with multiple vulnerabilities should be prioritized for intervention. Identifying and targeting them to offer help and support will be an effective approach.


Assuntos
Gastos em Saúde , Medicina Estatal , Idoso , China/epidemiologia , Características da Família , Feminino , Humanos , Seguro Saúde
15.
Mol Genet Genomic Med ; 9(9): e1760, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34387413

RESUMO

BACKGROUND: Rare diseases affect the health-related quality of life (HRQoL) of patients and their family caregivers (FCs). However, limited evidence is available on the HRQoL of FCs of patients with Gaucher disease (GD). This study aimed to assess HRQoL and related factors among FCs of patients with GD in China. METHODS: A cross-sectional online survey was conducted with 49 FCs recruited by convenience sampling. Participants completed the Medical Outcome Study Short Form-36 (SF-36), Zung's Self-Rating Anxiety Scale, Zung's Self-Rating Depression Scale, the Multi-dimensional Scale of Perceived Social Support, the Herth Hope Index, and a questionnaire about FCs' and patients' sociodemographic characteristics. Single-sample t tests, one-way analysis of variance, and multivariate linear regression analysis were used to analyze the data analysis. RESULTS: Participating FCs had significantly lower scores in all eight SF-36 domains compared with the general population in China (p < 0.01). FCs' gender, education, daily care time, anxiety, and the perceived disease severity of patients were significant predictors of SF-36 physical component summary scores. Caregiving help from others, anxiety, perceived disease severity, and medical insurance type were significant predictors of SF-36 mental component summary scores. CONCLUSION: The findings showed FCs of patients with GD had lower HRQoL. There is an urgent need to address the health concerns of FCs of people with rare diseases including their HRQoL.

16.
J Ethnopharmacol ; 280: 114480, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34358654

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Curcuma is a common Chinese herbal medicine that is used in the clinical treatment of chronic liver disease. Studies have found that curcumol is the main active ingredient of curcuma and has good hepatoprotective and anti-inflammatory effects. However, there are few reports on the molecular mechanism underlying the anti-liver fibrosis effect of curcumol. AIM: To explore the effect of curcumol on liver angiogenesis, and to reveal the mechanism of curcumol against liver fibrosis. MATERIALS AND METHODS: We used liver collagenase perfusion combined with Percoll density gradient sedimentation to separate primary liver sinusoidal endothelial cells, and then applied a leptin-activated cell pathological model. The cells were divided into four treatment groups as follows: blank group, model group, curcumol group, and solafini group. MTT was used to detect the cell proliferation rate in each group, and RT-PCR and western blotting were used to detect the expressions of VEGF, AKT, eNOS, CD31, and vWF. A fluorescent probe was used to detect NO expression, and scanning electron microscopy was used to observe changes in the cell fenestration structure. Angiogenesis assays were used to observe blood vessel formation in each group. RESULTS: The results of the MTT test found that the proliferation rate of each group was higher. The results of the molecular biology tests found that curcumol inhibited the activity of the VEGF/AKT/eNOS pathway, thereby increasing fenestration of sinusoidal endothelial cells and inhibiting liver angiogenesis. These differences were statistically significant compared with the model group. CONCLUSIONS: Curcumol inhibits the activity of the VEGF/AKT/eNOS signaling pathway, regulates the structure of hepatic sinusoidal endothelial cells, and inhibits liver angiogenesis, which together may explain its anti-liver fibrosis mechanism.

18.
Exp Ther Med ; 22(3): 1035, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34373721

RESUMO

As an important regulator involved in cell activity, microRNAs (miRNAs) are important in the process of exercise influencing bone metabolism. The present study aimed to detect and select differentially expressed miRNAs in the bone tissues of mice trained on a treadmill, predict the target genes of these differentially expressed miRNAs and lay a foundation for exploring the effect of treadmill training on bone metabolism through miRNAs. In this experiment, after the mice were trained on a treadmill for 8 weeks, the mechanical properties of mouse femur bone were assessed, and the alkaline phosphatase (ALP) activity and osteocalcin (OCN) protein levels of the bone were assayed. miRNA microarray and reverse transcription-quantitative (RT-q)PCR were performed to select and validate differentially expressed miRNAs in the bone, and the target genes of these miRNAs were predicted with bioinformatics methods. In addition, the differentially expressed miRNAs in the bone tissues were compared with those in mechanically strained osteocytes in vitro. Treadmill training improved the mechanical properties of the femur bones of mice, and elevated the ALP activity and OCN protein level in the bone. In addition, 122 differentially expressed miRNAs were detected in the bone, of which nine were validated via RT-qPCR. Among the target genes of these differentially expressed miRNAs, certain candidates were involved in bone metabolism. A total of eight miRNAs were differentially expressed in both bone tissue and osteocytes, exhibiting the same expression trends, and various target genes of these eight miRNAs were also involved in bone metabolism. Treadmill training resulted in altered miRNA expression profiles in the bones of mice (mainly in osteocytes) and the differentially expressed miRNAs may serve important roles in regulating bone metabolism and osteogenic differentiation.

19.
Methods Mol Biol ; 2358: 229-237, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34270059

RESUMO

Phosphorylation of a substrate by protein kinases leads to the activation or inactivation of numerous signaling pathways and metabolic processes. The assessment of kinase activity by using a specific or generic substrate plays a crucial role in characterization of kinase specificity and activity. Here we describe a protocol using either a synthetic peptide as a specific substrate or using myelin basic protein (MBP) as a generic substrate for the kinase activity assay. The kinase of interest is fused with a GFP (green fluorescent protein) tag and can be purified by GFP magnetic beads. Kinase-GFP complexes are then incubated with ATP, substrate, and coordinated reaction reagent for the kinase reaction. The assay is then quantified through mass spectrometry or enzymatic luminescence.

20.
Chin J Integr Med ; 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34319504

RESUMO

OBJECTIVE: To investigate the effect of curcumol on NOD-like receptor thermoprotein domain 3 (NLRP3) inflammasomes, and analyze the mechanism underlying curcumol against liver fibrosis. METHODS: Thirty Kunming mice were divided into a control group, a model group and a curcumol group according to a random number table, 10 mice in each group. Mice were intraperitoneally injected with 40% carbon tetrachloride (CCl4:peanut oil, 2:3 preparation) at 5 mL/kg for 6 weeks, twice a week, for developing a liver fibrosis model. The mice in the control group were given the same amount of peanut oil twice a week for 6 weeks. The mice in the curcumol group were given curcumol (30 mL/kg) intragastrically, and the mice in the model and control groups were given the same amount of normal saline once a day for 6 weeks. Changes in liver structure were observed by hematoxylin and eosin (HE) and Masson staining. Liver function, liver fiber indices, and the expression of interleukin (IL)-10 and tumor necrosis factor-α (TNF-α) levels were determined by automatic biochemical analyzer and enzyme linked immunosorbent assay kit. Immunoblotting and reverse transcription-quantitative PCR (RT-qPCR) were performed to detect the expression of NLRP3 inflammasome-related molecules, TGF-ß and collagen. RESULTS: HE and Masson staining results showed that the hepatocytes of the model group were arranged irregularly with pseudo-lobular structure and a large amount of collagen deposition. The mice in the curcumol group had a significant decrease in liver function and liver fibers indices compared with the model group (P<0.05); RT-qPCR and Western blotting results reveal that, in the curcumol group, the mRNA and protein expression levels of NLRP3, IL-1 ß, Caspase 1 and gasdermin D decreased significantly compared with the model group (P<0.05); immunohistochemical results showed that in the curcumol group, the protein expression levels of NLRP3 and IL-1 ß decreased significantly compared with the model group (P<0.05). CONCLUSION: A potential anti-liver fibrosis mechanism of curcumol may be associated with the inhibition of NLRP3 inflammasomes and decreasing the downstream inflammatory response.

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