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1.
Front Pediatr ; 10: 1046086, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36425399

RESUMO

Background: Exposure to disasters in early life may induce lifetime health risk, but investigation on earthquake exposure and DM in later life is still limited. The aim of the current study is to evaluate the association between exposure to the Tangshan Earthquake in early life and diabetes mellitus (DM) incidence in adulthood, and explore the modification of lifestyles on DM development. Methods: Participants who were free of DM at baseline from the Kailuan Study were included in this study. All participants were divided into fetal-exposed, infant-exposed, early childhood-exposed and nonexposed group. The effect of earthquake exposure on DM and modification of lifestyles were examined by multivariable-adjusted Cox proportional hazard model. Results: The exposed group had a higher risk of DM than nonexposed group, especially in infant-exposed and early childhood-exposed group, with hazard ratio (HR) of 1.62 [95% confidence intervals (CI), 1.21-2.17] and 1.46 (95% CI, 1.06-1.99), respectively. After stratifying by lifestyles, a significant modification was observed in alcohol consumption. Conclusion: Exposing to earthquake in early life could increase DM incidence in later life, and alcohol consumption might modify the effect of earthquake exposure on DM development. More attention should be paid on the preventions of DM among adults who exposed to earthquake in their early life.

2.
J Psychiatr Res ; 156: 705-712, 2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36410309

RESUMO

Altered network organization and aberrant neurometabolic levels have been associated with schizophrenia. However, modular alterations of functional-neurometabolic coupling in various stages of schizophrenia remain unclear. This longitudinal study enrolled 34 drug-naïve first-episode schizophrenia (FES) patients and 30 healthy controls (HC). The FES patients underwent resting-state functional magnetic resonance imaging (rs-fMRI) and proton magnetic resonance spectroscopy (1H-MRS) at baseline, 2 months, and 6 months of treatment. For 1H-MRS, the concentrations of γ-aminobutyric acid (GABA), N-acetylaspartate (NAA) and glutamate + glutamine in the ventromedial prefrontal cortex region were measured. A graph theoretical approach was applied for functional connectivity-based modular parcellation. We found that intra-default mode network (DMN) connectivity, inter-modular connectivity between the DMN and the hippocampus, and inter-modular connectivity between the DMN and the frontoparietal module were significantly different across 6-month treatment in the FES patients. The inter-module connectivity of the DMN and hippocampus correlated positively with NAA concentration in the HC group, while this correlation was absent in FES patients. This exploratory study suggests an altered modular connectivity in association with neurometabolite concentrations in FES patients and provides insights into multimodal neuroimaging biomarkers in schizophrenia. Future studies with larger sample sizes are needed to consolidate our findings.

3.
J Fungi (Basel) ; 8(11)2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36354942

RESUMO

Pestalotiod fungi are associated with a wide variety of plants worldwide and occur as endophytes, pathogens, and saprobes. The present study provides an updated phylogeny for genera Neopestalotiopsis, Pestalotiopsis, and Seiridium using fresh collections from woody oil plants (Camellia oleifera, Olea europaea, Paeonia suffruticosa, Sapium sebiferum, and Vernicia fordii) in Sichuan Province, China. We coupled morphology and combined sequence data analyses of ITS, tub2, and tef1-α for Neopestalotiopsis and Pestalotiopsis, with ITS, LSU, tub2, tef1-α, and rpb2 for Seiridium. Three novel species of Neopestalotiopsis (N. mianyangensis, N. paeonia-suffruticosa, N. terricola) and three of Seiridium (S. guangyuanum, S. vernicola, S. oleae), were found. Three other species, Pestalotiopsis kenyana, Seiridium ceratosporum, and S. rosarum were identified and reported as new records. All isolated species are fully described and illustrated. Additionally, the sexual morph of Pestalotiopsis kenyana is described for the first time. Pathogenicity tests revealed that Neopestalotiopsis mianyangensis, N. paeonia-suffruticosa, N. terricola, Pestalotiopsis kenyana, Seiridium guangyuanum, S. vernicola, and S. oleae are pathogenic on detached olive leaves.

4.
Sci Rep ; 12(1): 20313, 2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36446824
5.
Artigo em Inglês | MEDLINE | ID: mdl-36197615

RESUMO

Ozone pollution in China has gradually increased, attracting extensive attention. Existing studies on ozone pollution typically take environmental and chemical perspectives. As air pollution is closely related to social and economic activities, it is also important to study ozone pollution from a socioeconomic perspective. Using the association rule mining technique, we uncovered hidden patterns between ozone variance and socioeconomic factors in macro-, meso-, and micro-scenarios in 297 Chinese cities. We found that the acceleration of urbanization and industrialization has indeed aggravated urban ozone pollution. The supply of water and power resources may be a significant factor influencing urban ozone pollution. Transportation hub cities with more developed economies and industries are more likely to suffer from ozone pollution in summer and autumn. Human behavior is a critical factor influencing the weekly variance in ozone concentration during weekdays and weekends. The influence of plant-derived VOC emissions on the formation of ozone cannot be overlooked. Our results deepen the understanding of ozone pollution in Chinese cities, and we provide corresponding policy recommendations to alleviate ozone pollution and improve air quality.

6.
Zhongguo Yi Liao Qi Xie Za Zhi ; 46(5): 538-544, 2022 Sep 30.
Artigo em Chinês | MEDLINE | ID: mdl-36254483

RESUMO

Sampling inspection by attributes is one of the most popular means for quality control of medical devices, and has widespread application in the process of production and supervision. GB/T 2828 series standards list different types of sampling procedures for inspection by attributes. This study introduced GB/T 2828 series standards and how to design and index the sampling schemes under different scenarios. At the same time, it also provided suggestions on how to balance accuracy and economy, which can provide guidance the application of medical devices manufactures and regulatory departments.


Assuntos
Comércio , Controle de Qualidade , Padrões de Referência
7.
Sensors (Basel) ; 22(20)2022 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-36298405

RESUMO

To improve the satisfaction and acceptance of automatic driving, we propose a deep reinforcement learning (DRL)-based autonomous car-following (CF) decision-making strategy using naturalist driving data (NDD). This study examines the traits of CF behavior using 1341 pairs of CF events taken from the Next Generation Simulation (NGSIM) data. Furthermore, in order to improve the random exploration of the agent's action, the dynamic characteristics of the speed-acceleration distribution are established in accordance with NDD. The action's varying constraints are achieved via a normal distribution 3σ boundary point-to-fit curve. A multiobjective reward function is designed considering safety, efficiency, and comfort, according to the time headway (THW) probability density distribution. The introduction of a penalty reward in mechanical energy allows the agent to internalize negative experiences. Next, a model of agent-environment interaction for CF decision-making control is built using the deep deterministic policy gradient (DDPG) method, which can explore complicated environments. Finally, extensive simulation experiments validate the effectiveness and accuracy of our proposal, and the driving strategy is learned through real-world driving data, which is better than human data.


Assuntos
Condução de Veículo , Automóveis , Humanos , Aceleração , Simulação por Computador , Recompensa
8.
Front Psychol ; 13: 962084, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36092112

RESUMO

Carbon emission trading is not only a market-based instrument but also one of the government's macro-policies, which is extremely crucial to fulfilling both carbon peak attainment and carbon neutrality goals. For this purpose, this paper adopts a 30-region dataset for the period from 2008 to 2020 in China and employs the difference-in-difference (DID) method to quantify the effect of the carbon emission trading pilot policy (CETP) on carbon emissions on the basis of introducing industrial structure upgrading and green technology innovation as moderating variables. The results show that (1) CETP has a statistically significant dampening effect on carbon emissions, while its carbon emission reduction effect follows a significant strengthening trend as the policy year of CETP implementation is delayed. (2) CETP has a significant carbon emission reduction effect. However, its effect demonstrates a gradual decrease from the eastern to the central and finally to the western regions. (3) CETP can inhibit carbon emissions depending on industrial structure upgrading to a certain extent, and this dependence is significant in the national and eastern regions but not in the central and western regions. (4) CETP's carbon emission reduction effect is dependent on green technology innovation, which is only revealed in the western region and performs as a dampening effect in the national, eastern, and central regions, but not significantly.

9.
New Phytol ; 236(6): 2233-2248, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36059081

RESUMO

Although some nucleotide binding, leucine-rich repeat immune receptor (NLR) proteins conferring resistance to specific viruses have been identified in dicot plants, NLR proteins involved in viral resistance have not been described in monocots. We have used map-based cloning to isolate the CC-NB-LRR (CNL) Barley stripe mosaic virus (BSMV) resistance gene barley stripe resistance 1 (BSR1) from Brachypodium distachyon Bd3-1 inbred line. Stable BSR1 transgenic Brachypodium line Bd21-3, barley (Golden Promise) and wheat (Kenong 199) plants developed resistance against BSMV ND18 strain. Allelic variation analyses indicated that BSR1 is present in several Brachypodium accessions collected from countries in the Middle East. Protein domain swaps revealed that the intact LRR domain and the C-terminus of BSR1 are required for resistance. BSR1 interacts with the BSMV ND18 TGB1 protein in planta and shows temperature-sensitive antiviral resistance. The R390 and T392 residues of TGB1ND (ND18 strain) and the G196 and K197 residues within the BSR1 P-loop motif are key amino acids required for immune activation. BSR1 is the first cloned virus resistance gene encoding a typical CNL protein in monocots, highlighting the utility of the Brachypodium model for isolation and analysis of agronomically important genes for crop improvement.


Assuntos
Brachypodium , Hordeum , Hordeum/genética , Brachypodium/genética , Proteínas de Repetições Ricas em Leucina , Domínios Proteicos
10.
Front Pharmacol ; 13: 950156, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36046831

RESUMO

Histocompatibility Minor 13 (HM13) encoding the signal peptide peptidase plays an important role in maintaining protein homeostasis but its role in tumors remains unclear. In this study, 33 tumor RNA-seq datasets were extracted from The Cancer Genome Atlas (TCGA) database, and the pan-cancer expression profile of HM13 was evaluated in combination with The Genotype-Tissue Expression (GTEx) datasets. The prognostic significance of abnormal HM13 pan-cancer expression was evaluated by univariate Cox regression and Kaplan-Meier analyses. Co-expression analysis was performed to examine the correlation between abnormal pan-cancer expression of HM13 and immune cell infiltration, immune checkpoint, molecules related to RNA modification, tumor mutational burden (TMB), microsatellite instability (MSI), and other related molecules. CellMiner database was used to evaluate the relationship between the expression of HM13 and drug sensitivity. The results showed overexpression of HM13 in almost all tumors except kidney chromophobe (KICH). Abnormally high expression of HM13 in adrenocortical carcinoma (ACC), kidney renal papillary cell carcinoma (KIRP), uveal melanoma (UVM), liver hepatocellular carcinoma (LIHC), brain lower grade glioma (LGG), head and neck squamous cell carcinoma (HNSC), and kidney renal clear cell carcinoma (KIRC) was associated with poor prognosis. Expression of HM13 correlated strongly with pan-cancer immune checkpoint gene expression and immune cell infiltration. Drug sensitivity analysis indicated that the expression of HM13 was an excellent predictor of drug sensitivity. We verified that both mRNA and protein levels of HM13 were abnormally upregulated in HCC tissues, and were independent risk factors for poor prognosis. Furthermore, interference with HM13 expression in Huh-7 and HCCLM3 cells significantly inhibited proliferation, migration, and invasion. Therefore, our findings demonstrate that HM13 is a potential pan-cancer prognostic marker, thus providing a new dimension for understanding tumor development.

11.
Asia Pac J Oncol Nurs ; 9(8): 100107, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36033969

RESUMO

A primary cancer diagnosis has been confirmed as an important risk factor for falls, and the incidence of falls has been shown to be higher in patients who have undergone cancer treatment than in those who have not undergone cancer treatment. Falls during hospitalization increase the medical costs of additional treatment and falls-related mortality. Many falls are preventable and a good understanding of the predictors of falls in this population is needed. However, the risk factors for falls have not yet been identified. The purpose of this review was to identify the risk factors for falls in hospitalized patients with cancer. Eleven English and Chinese electronic databases were searched from their inception to April 2022 and the methodological quality of the included studies was assessed using the Newcastle-Ottawa Quality Assessment Scale. Five studies involving 1237 patients with cancer were included. The meta-analysis identifies eleven risk factors for falls in hospitalized patients with cancer, including age, history of falls, opiates, benzodiazepines, steroids, antipsychotics, sedatives, radiation therapy, chemotherapy, the use of an assistive device and length of hospitalization. Based on the evidence presented in this article, healthcare workers have the capacity to help reduce fall risk through the development of preventive support strategies in this population. Multicenter, prospective studies of patients with cancer should be conducted to further identify and validate their risk factors for falls.

12.
J Med Virol ; 94(12): 6016-6022, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35922376

RESUMO

The seroprevalence of Kaposi's sarcoma-associated herpesvirus (KSHV) is high in Xinjiang, China. But the seroprevalence of KSHV and risk factors are still unknown in Gansu which is adjacent to Xinjiang. Six hundred and seventy-eight serum samples of the general population and 87 serum samples of syphilis patients from Jiuquan, Gansu were tested for antibodies against KSHV, including one latent protein (ORF73) and two lytic proteins (ORF65 and K8.1) using the ELISA. The total KSHV-seropositive rate was 15.9% in 678 serum samples in the Jiuquan area, and the KSHV-seropositive rate of males was higher than females (18.0% vs. 14.6%, p > 0.05). The Uygur, Kazakh, Hui, Manchu, and Mongolian populations had a higher seroprevalence of KSHV than the Han population (43.8%, 40.0%, 34.5%, 30.3%, 35.0% vs. 11.0%, respectively) among the ethnic groups in Jiuquan. Compared to the Han, Uygur, Kazak, Hui, Manchu, and Mongolian people had an increase in the risk of KSHV of 528.9%, 439.1%, 325.6%, 251.6%, and 335.4% (p < 0.001, p < 0.001, p < 0.001, p = 0.002, p = 0.003, respectively). The serum prevalence of KSHV in subjects aged < 20 years, 20-50 years, and >50 years was 13.8%, 14.7%, and 20.1%, respectively. Compared to the subjects aged < 20 years, 20-50 years and >50 years had an increase in the risk of KSHV of 7.4% and 56.9% (p = 0.829 and p = 0.204, respectively). Compared to the positive rate of KSHV in the general population of Anhui, the positive rate of KSHV was significantly higher in the general population of the Jiuquan area (15.9% vs. 9%, p < 0.01). There was no significant difference in the positive rate of KSHV between the Han population of Jiuquan and the Han population of Anhui (p > 0.05). In the population of syphilis patients in the Jiuquan area, the positive rate of KSHV was 30.7%, which was higher than that of the general population in the Gansu area (p < 0.05). This study indicates that Gansu has a high seroprevalence of KSHV. Ethnicity and syphilis are risk factors for KSHV infection.


Assuntos
Herpesvirus Humano 8 , Sarcoma de Kaposi , Sífilis , Anticorpos Antivirais , China/epidemiologia , Feminino , Humanos , Masculino , Fatores de Risco , Estudos Soroepidemiológicos
13.
Chem Biol Interact ; 365: 110070, 2022 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-35921950

RESUMO

Thymoquinone, predominant bioactive compound in Nigella sativa L. (N.sativa) oil, may inhibit the activity of cytochrome P450 2C9 (CYP2C9). However, it is not clear whether thymoquinone can affect the pharmacokinetic behavior of warfarin. Thus, we further to investigate the effect of thymoquinone on warfarin 7-hydroxylation activity and to quantitatively evaluate their food-drug interactions (FDIs) potential. Our data demonstrated that thymoquinone could inhibit warfarin 7-hydroxylase activity with IC50 value of 11.35 ± 0.25 µM. The kinetic analysis indicated that thymoquinone exhibited competitive inhibition on warfarin 7-hydroxylation with Ki value of 3.50 ± 0.44 µM. FDIs risk prediction suggested that coadministration of thymoquinone (>18 mg/day) or dietary supplements containing thymoquinone (N.sativa > 1 g/day or N. sativa oil >1 g/day) might influence pharmacokinetic behavior of warfarin. In conclusion, coadministration of thymoquinone or dietary supplements containing thymoquinone in warfarin-treated patients would likely trigger off unexpected potential drug interactions.


Assuntos
Interações Alimento-Droga , Varfarina , Benzoquinonas/farmacologia , Citocromo P-450 CYP2C9/metabolismo , Humanos , Cinética , Varfarina/farmacologia
14.
J Physiol Biochem ; 2022 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-35984620

RESUMO

Exosomes have a critical role in the intercellular communication and metastatic progression of hepatocellular carcinoma (HCC). Recently, our group showed that α2, 6-sialylation played an important role in the proliferation- and migration-promoting effects of cancer-derived exosomes. However, the molecular basis remains elusive. In this study, the mechanism of α2, 6-sialylation-mediated specific microRNAs (miRNA) sorting into exosomes was illustrated. We performed miRNA profiling analysis to compare exosomes from HCC cell lines that differ only in α2, 6-sialylation status. A total of 388 differentially distributed miRNAs were identified in wild-type and ß-galactoside α2, 6-sialyltransferase I (ST6Gal-I) knockdown MHCC-97H cells-derived exosomes. Neutral sphingomyelinase-2 (nSmase2), an important regulator mediating the sorting of exosomal miRNAs, was found to be a target of ST6Gal-I. The reduction of α2, 6-sialylation could impair the activity of nSmase2, as well as the nSmase2-dependent exosomal miRNAs sorting. This α2,6-sialylation-dependent sorting exerted an augmentation of motility on recipient HCC cells. Our data further demonstrated that α2,6-sialylation-mediated sorting of exosomal miR-100-5p promoted the migration and invasion of recipient HepG2 cells via the PI3K/AKT signaling pathway. The cellular metastasis-related gene CLDN11 was confirmed as a direct target of exosomal miR-100-5p, which elevated the mobility of recipient HCC cells. In conclusion, our results showed that α2,6-sialylation modulates nSmase2-dependent exosomal miRNAs sorting and promotes HCC progression.

15.
Sci Total Environ ; 851(Pt 1): 157954, 2022 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-35963410

RESUMO

Given the possible ecological dangers of graphene oxide (GO), a thorough understanding of its aggregation behavior is essential. During industrial applications, GOs may be used as multi-layered, and there is some possibility that GOs are released into the water environment in the aggregated state. Thus, elucidating the fate of aggregated GO is valuable for evaluating their environmental fate. In this work, the effect of pH on the fate of aggregated graphene oxide (GO) was explored using experimental measurements and molecular dynamic simulations and promoted aggregation of GO upon the increase of pH was observed. Additional investigations show that the presence of oxidation debris (ODs) on GO served as the primary driver of the unanticipated trend in aggregation behavior. GO consists of lightly oxidized functionalized graphene sheets and highly oxidized ODs. Upon the increase of pH and the deprotonation of functional groups, ODs are stripped from GO due to electrostatic repulsions and steric hindrance of water molecules. The stripping of ODs decreased the zeta potential and increased the hydrophobicity of GO, thus accelerating the aggregation. Additionally, the stripped ODs may recombine to GO edges and bridged GOs, which also contribute to further aggregation. Functional group deprotonation, ODs stripping, OD bridging, double layer compression, and charge neutralization all worked together to promote aggregation, resulting in the formation of FG-water-OD aggregates. Overall, the presence of ODs complicates the structures and properties of GO and should be considered during the development of GO-related nanomaterials and the evaluation of their environmental impact.


Assuntos
Grafite , Grafite/química , Concentração de Íons de Hidrogênio , Simulação de Dinâmica Molecular , Óxidos/química , Água/química
16.
J Invertebr Pathol ; 194: 107816, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35964678

RESUMO

Inhibitor of apoptosis protein 1 (IAP1) of Antheraea pernyi multinucleocapsid nucleopolyhedrovirus (AnpeNPV) belongs to the baculovirus IAP1 type. The function of AnpeNPV-IAP1 in viral replication and occlusion body (OB) production remains unknown. In this study, we demonstrated that AnpeNPV-iap1 is a late gene. AnpeNPV-IAP1 mainly localizes to the nuclear ring zone and exhibits dynamic distribution in the cytoplasm and the virogenic stroma during AnpeNPV infection. AnpeNPV-IAP1 impacted the expression of a variety of viral genes at the very late phase of infection in Tn-Hi5 cells. The deletion of AnpeNPV-iap1 caused decreased expression levels of polyhedrin, morphological changes to OBs and reduced OB production in A. pernyi pupae, along with a lengthening of the lethal time of A. pernyi larvae. These results suggest that AnpeNPV-iap1 is involved in regulating viral gene expression, OB production and morphogenesis in A. pernyi.


Assuntos
Mariposas , Nucleopoliedrovírus , Animais , Proteína 3 com Repetições IAP de Baculovírus , Nucleopoliedrovírus/genética , Replicação Viral
17.
Materials (Basel) ; 15(15)2022 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-35955266

RESUMO

Due to the advantages of high specific strength, specific stiffness, and excellent fatigue resistance, carbon fiber reinforced braided composites have been widely applied in engineering. Since the molding process of braided composites is complex and immature, substantial variability of the internal geometry exists in composites, in which the yarn path with uncertainty is a main factor, so it is necessary to establish an uncertainty model to study the influence of randomness of the yarn path on mechanical properties, which is significantly related to the fatigue resistance properties of composite. An uncertain mesoscopic model with uniform distribution of yarn paths is proposed. Assuming the yarn path is spatially varying in interval range, the variability of yarn path is represented geometrically in the unit cell of composite. The three-dimensional coordinates of the yarn trajectory are calculated, the meso-uncertainty models of 2-D and 2.5-D braided composites are established. The equivalent elastic parameters and the thermal expansion coefficients are obtained by applying homogenization method and temperature field boundary conditions to the mesoscopic model. The effect of yarn path uncertainty on the statistical characteristics of elastic and thermal parameters of braided composites was studied by using Monte-Carlo simulation. A simulation method for modeling yarn path uncertainty of braided composites is provided in this paper for predicting the statistical characteristics of the equivalent elastic and thermal parameters.

18.
Front Genet ; 13: 900380, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35836576

RESUMO

Background: This study aimed to screen potential drugs targeting a new prognostic gene signature associated with proliferation in hepatocellular carcinoma (HCC). Methods: CRISPR Library and TCGA datasets were used to explore differentially expressed genes (DEGs) related to the proliferation of HCC cells. Differential gene expression analysis, univariate COX regression analysis, random forest algorithm and multiple combinatorial screening were used to construct a prognostic gene signature. Then the predictive power of the gene signature was validated in the TCGA and ICGC datasets. Furthermore, potential drugs targeting this gene signature were screened. Results: A total of 640 DEGs related to HCC proliferation were identified. Using univariate Cox analysis and random forest algorithm, 10 hub genes were screened. Subsequently, using multiplex combinatorial screening, five hub genes (FARSB, NOP58, CCT4, DHX37 and YARS) were identified. Taking the median risk score as a cutoff value, HCC patients were divided into high- and low-risk groups. Kaplan-Meier analysis performed in the training set showed that the overall survival of the high-risk group was worse than that of the low-risk group (p < 0.001). The ROC curve showed a good predictive efficiency of the risk score (AUC > 0.699). The risk score was related to gene mutation, cancer cell stemness and immune function changes. Prediction of immunotherapy suggetsted the IC50s of immune checkpoint inhibitors including A-443654, ABT-888, AG-014699, ATRA, AUY-922, and AZ-628 in the high-risk group were lower than those in the low-risk group, while the IC50s of AMG-706, A-770041, AICAR, AKT inhibitor VIII, Axitinib, and AZD-0530 in the high-risk group were higher than those in the low-risk group. Drug sensitivity analysis indicated that FARSB was positively correlated with Hydroxyurea, Vorinostat, Nelarabine, and Lomustine, while negatively correlated with JNJ-42756493. DHX37 was positively correlated with Raltitrexed, Cytarabine, Cisplatin, Tiotepa, and Triethylene Melamine. YARS was positively correlated with Axitinib, Fluphenazine and Megestrol acetate. NOP58 was positively correlated with Vorinostat and 6-thioguanine. CCT4 was positively correlated with Nerabine. Conclusion: The five-gene signature associated with proliferation can be used for survival prediction and risk stratification for HCC patients. Potential drugs targeting this gene signature deserve further attention in the treatment of HCC.

19.
Oxid Med Cell Longev ; 2022: 2606928, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35799889

RESUMO

According to numerous animal studies, adverse environmental stimuli, including physical, chemical, and biological factors, can cause low-grade chronic inflammation and subsequent tumor development. Human epidemiological evidence has confirmed the close relationship between chronic inflammation and tumorigenesis. However, the mechanisms driving the development of persistent inflammation toward tumorigenesis remain unclear. In this study, we assess the potential role of reactive oxygen species (ROS) and associated mechanisms in modulating inflammation-induced tumorigenesis. Recent reports have emphasized the cross-talk between oxidative stress and inflammation in many pathological processes. Exposure to carcinogenic environmental hazards may lead to oxidative damage, which further stimulates the infiltration of various types of inflammatory cells. In turn, increased cytokine and chemokine release from inflammatory cells promotes ROS production in chronic lesions, even in the absence of hazardous stimuli. Moreover, ROS not only cause DNA damage but also participate in cell proliferation, differentiation, and apoptosis by modulating several transcription factors and signaling pathways. We summarize how changes in the redox state can trigger the development of chronic inflammatory lesions into tumors. Generally, cancer cells require an appropriate inflammatory microenvironment to support their growth, spread, and metastasis, and ROS may provide the necessary catalyst for inflammation-driven cancer. In conclusion, ROS bridge the gap between chronic inflammation and tumor development; therefore, targeting ROS and inflammation represents a new avenue for the prevention and treatment of cancer.


Assuntos
Neoplasias , Animais , Carcinogênese/patologia , Transformação Celular Neoplásica , Inflamação/metabolismo , Neoplasias/patologia , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Microambiente Tumoral
20.
Open Life Sci ; 17(1): 744-755, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35891967

RESUMO

We investigated the role of the interaction between the Notch and Toll-like receptor 4 (TLR4) pathways in septic myocardial injury. The sepsis model was induced in rats with lipopolysaccharide (LPS). Rats were divided into control, LPS, LPS + TAK242 ((6R)-6-[N-(2-chloro-4-fluorophenyl)sulfamoyl]cyclohex-1-ene-1-carboxylate) and LPS + DAPT (N-[N-(3,5-difluorophenacetyl)-l-alanyl]-s-phenylglycinetbutylester) groups. Heart function was evaluated with a Cardiac Doppler ultrasound. Myocardial morphological changes were detected by hematoxylin-eosin staining (H&E). Apoptosis was assessed by a TUNEL assay. The mRNA and protein levels were detected with real-time PCR, Western blot, and immunohistochemistry analysis. We found that heart function in the LPS + TAK242 group was significantly improved, but not in the LPS + DAPT group. LPS + TAK242 had a lower level of degeneration and necrosis of cardiomyocytes and inflammatory cell infiltration, as well as lower apoptosis and caspase-3 expression than the LPS group. Compared with the LPS group, the inflammatory cell infiltration was reduced in the LPS + DAPT group, while the degeneration and necrosis of cardiomyocytes were not obviously improved. Additionally, the expression levels of tumor necrosis factor-α and Interleukin-6, the protein contents of Notch intracellular domain and Hes1, and the P65 nuclear factor kappa-B (NF-κB) to P-P65 NF-κB ratio in LPS + TAK242 group and LPS + DAPT group were significantly lower than those in LPS group. Conclusively, the interaction between TLR4 and Notch signaling pathways enhances the inflammatory response in the septic heart by activating NF-κB. Blocking the TLR4 pathway with TAK242 can improve heart dysfunction and myocardial damage in sepsis, while blocking the Notch pathway with DAPT cannot effectively prevent heart dysfunction and myocardial damage in sepsis.

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