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1.
Int J Biol Macromol ; : 123338, 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36706881

RESUMO

In this study, we innovatively synthesized a multifunctional PVA/PU-LNP composite hydrogel with integrated distinguished UV-blocking, mechanical strength, dynamic viscoelasticity and thermal properties by introducing lignin nanoparticle (LNP) into polyvinyl alcohol (PVA) and polyurethane (PU) mixed matrix through freeze-thaw cycle. The rigid porous network structure was established by hydrogen bond interactions among the well-distributed LNP and PVA/PU molecular chains, which endowed excellent mechanical strength, viscoelasticity, thermal stability and flexibility with PVA/PU-LNP composite hydrogel. The elongation at break and tensile strength of PVA/PU-LNP composite hydrogel were markedly improved from 227.3 % and 247.1 KPa to 460.1 % and 950.4 KPa with the LNP loading of 2 % based on PVA weight, respectively. Meanwhile, PVA/PU-2%LNP hydrogel exhibited prominent compressive resistance and pleasing shape recovery capability. Moreover, the blending of LNP at a low dosage (0.5 %) based on PVA weight effectively shielded 99.34 % of UV light and penetrated 42.27 % of visible light, indicating that PVA/PU-LNP composite hydrogel demonstrated outstanding anti-UV performance. In addition, the incorporation of LNP caused a remarkable decline in the pore size of PVA/PU-LNP composite hydrogel (4.39 ±â€¯0.46 µm to 1.54 ±â€¯0.22 µm), which slightly reduced water uptake capacity of composite hydrogel. Therefore, this work provided a new approach to constructing a multifunctional composite hydrogel.

2.
Biomolecules ; 13(1)2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36671532

RESUMO

Ferroptosis is a new form of iron-dependent cell death and plays an important role during the occurrence and development of various tumors. Increasingly, evidence shows a convincing interaction between ferroptosis and tumor immunity, which affects cancer patients' prognoses. These two processes cooperatively regulate different developmental stages of tumors and could be considered important tumor therapeutic targets. However, reliable prognostic markers screened based on the combination of ferroptosis and tumor immune status have not been well characterized. Here, we chose the ssGSEA and ESTIMATE algorithms to evaluate the ferroptosis and immune status of a TCGA breast invasive ductal carcinoma (IDC) cohort, which revealed their correlation characteristics as well as patients' prognoses. The WGCNA algorithm was used to identify genes related to both ferroptosis and immunity. Univariate COX, LASSO regression, and multivariate Cox regression models were used to screen prognostic-related genes and construct prognostic risk models. Based on the ferroptosis and immune scores, the cohort was divided into three groups: a high-ferroptosis/low-immune group, a low-ferroptosis/high-immune group, and a mixed group. These three groups exhibited distinctive survival characteristics, as well as unique clinical phenotypes, immune characteristics, and activated signaling pathways. Among them, low-ferroptosis and high-immune statuses were favorable factors for the survival rates of patients. A total of 34 differentially expressed genes related to ferroptosis-immunity were identified among the three groups. After univariate, Lasso regression, and multivariate stepwise screening, two key prognostic genes (GNAI2, PSME1) were identified. Meanwhile, a risk prognosis model was constructed, which can predict the overall survival rate in the validation set. Lastly, we verified the importance of model genes in three independent GEO cohorts. In short, we constructed a prognostic model that assists in patient risk stratification based on ferroptosis-immune-related genes in IDC. This model helps assess patients' prognoses and guide individualized treatment, which also further eelucidatesthe molecular mechanisms of IDC.


Assuntos
Carcinoma Ductal , Ferroptose , Humanos , Ferroptose/genética , Algoritmos , Morte Celular , Ferro
3.
Fitoterapia ; 165: 105425, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36608712

RESUMO

Huperzine A, a lycodine-type alkaloid, exhibits potent inhibitory activity against acetylcholinesterase (AChE) and has been utilized to treat neurodegenerative diseases' symptoms. Lycopodiastrum casuarinoides, a member of the family Lycopodiaceae, is renowned for its lycodine-type alkaloids. Some of these alkaloids show various pharmacological benefits, such as anti-cholinesterase, neuroprotective, and cytotoxic effects. To date, 113 chemical compounds, including seventy-four lycodine-type alkaloids, ten terpenoids, eleven aliphatics, and eighteen other compounds, have been isolated from this plant. In this review, we have discussed phytochemicals and biological activities of the reported compounds of L. casuarinoides. Moreover, structure-activity relationship (SAR), plausible biosynthetic pathways, and 13C nuclear magnetic resonance spectroscopy (13C NMR) data of the lycodine-type alkaloids are also summarized.

5.
Environ Res ; 221: 115290, 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36642121

RESUMO

Nuclear power has received renewed attention during the energy transition in recent years. This study is aimed to explore whether nuclear energy can promote economic growth without increasing carbon emissions. In order to have a more comprehensive understanding of the relationship between nuclear energy, economic growth, and carbon emissions, this study also discusses the impact of coal, oil, natural gas, and renewable energy on economic growth and carbon emissions. The second-generation panel unit root test, panel cointegration test, panel fully modified ordinary least squares, and Heterogeneous Dumitrescu and Hurlin causality test were used to estimate the long-term elasticity and causality among variables. Results based on panel data from 24 countries with nuclear energy from 2001 to 2020 show that both nuclear energy and renewable energy can curb carbon emissions. Especially in Canada, Finland, Russia, Slovenia, South Korea, and The United Kingdom, nuclear energy reduces carbon emissions more significantly than renewable energy. Meanwhile, there is a positive relationship between increased nuclear energy, increased renewable energy, and economic growth, which means that nuclear energy and renewable energy could increase economic growth as well. There is a positive relationship between increased oil, increased natural gas, and economic growth, while there is a negative relationship between the increase in coal and economic growth. Meanwhile, there is a positive relationship between increased oil, increased coal, and increased carbon emissions, while the positive relationship between increased natural gas and increased carbon emissions is not significant. Thus, in the 22 countries with nuclear power, increased coal consumption does not drive economic growth but increases carbon emissions. Increased oil consumption increases economic growth, but it increases carbon emissions. Increased natural gas consumption boosts economic growth but adds little to carbon emissions. In the authors' view, nuclear power and renewable energy are all options for these nuclear-power countries to pursue economic growth without increasing carbon emissions. Moreover, nuclear power has a better effect on curbing carbon emissions in some countries than renewable energy. Therefore, under the premise of safety, nuclear power should be seriously considered and re-developed.

6.
Mol Cancer ; 22(1): 16, 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36691031

RESUMO

BACKGROUND: hsa_circ_0001727 (circZKSCAN1) has been reported to be a tumor-associated circRNA by sponging microRNAs. Intriguingly, we found that circZKSCAN1 encoded a secretory peptide (circZKSaa) in the liver. The present study aims to elucidate the potential role and molecular mechanism of circZKSaa in the regulation of hepatocellular carcinoma (HCC) progression. METHODS: The circRNA profiling datasets (RNA-seq data GSE143233 and GSE140202) were reanalyzed and circZKSCAN1 was selected for further study. Mass spectrometry, polysome fractionation assay, dual-luciferase reporter, and a series of experiments showed that circZKSCAN1 encodes circZKSaa. Cell proliferation, apoptosis, and tumorigenesis in nude mice were examined to investigate the functions of circZKSaa. Mechanistically, the relationship between the circZKSaa and mTOR in HCC was verified by immunoprecipitation analyses, mass spectrometry, and immunofluorescence staining analyses. RESULTS: Receiver operating characteristic (ROC) analysis demonstrated that the secretory peptide circZKSaa encoded by circZKSCAN1 might be the potential biomarker for HCC tissues. Through a series of experiments, we found that circZKSaa inhibited HCC progression and sensitize HCC cells to sorafenib. Mechanistically, we found that the sponge function of circZKSCAN1 to microRNA is weak in HCC, while overexpression of circZKSaa promoted the interaction of FBXW7 with the mammalian target of rapamycin (mTOR) to promote the ubiquitination of mTOR, thereby inhibiting the PI3K/AKT/mTOR pathway. Furthermore, we found that the high expression of cicZKSCAN1 in sorafenib-treated HCC cells was regulated by QKI-5. CONCLUSIONS: These results reveal that a novel circZKSCAN1-encoded peptide acts as a tumor suppressor on PI3K/AKT/mTOR pathway, and sensitizes HCC cells to sorafenib via ubiquitination of mTOR. These findings demonstrated that circZKSaa has the potential to serve as a therapeutic target and biomarker for HCC treatment.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Animais , Camundongos , Carcinoma Hepatocelular/genética , RNA Circular/genética , Neoplasias Hepáticas/genética , Sorafenibe , Proteínas Proto-Oncogênicas c-akt/metabolismo , Sirolimo , Fosfatidilinositol 3-Quinases/metabolismo , Camundongos Nus , MicroRNAs/genética , Serina-Treonina Quinases TOR/metabolismo , Proliferação de Células/genética , Peptídeos/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Mamíferos/genética , Mamíferos/metabolismo
7.
Plast Reconstr Surg ; 2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36700876

RESUMO

BACK GROUND: Capsular contracture was the most common complication of breast implantation surgery. Bacterial contamination was considered to play an important role in the occurrence of capsular contracture, and Gram-positive bacteria like Staphylococcus epidermidis were discovered in the clinical specimens. Lipoteichoic acid (LTA) was a component of Gram-positive bacteria cell wall, and was sufficient in the pathogenicity of the bacteria. We assumed that LTA could trigger the immunological response against the implant and cause capsular contracture. METHODS: We developed a rat model of capsular contracture by repeated injection of 10 µg/ml LTA. The histological changes of the capsule tissue were measured by HE, Sirius Red, Masson and Immunohistochemical staining. The expression of related cytokines was measured by qRT-PCR. The downstream pathway activation was shown by Western blot. We also applied Tocilizumab, an IL-6 receptor antagonist, to verify the role of IL-6 in this pathological process. RESULTS: We discovered that repeated LTA injection, at a low concentration, could induce the thickening of capsule tissue, the deposition of collagen fiber and the activation of myofibroblasts. IL-6/STAT3 signaling pathway was activated in this process, and the inhibition of IL-6 receptor could relieve the symptoms. B cells and T-helper cells, especially T-helper 1, could be related to this phenomenon. CONCLUSIONS: Our research corroborated that subclinical infection could trigger capsular contracture, and the immune system played an important role in this process. Our results provided a possible research direction for the mechanism of bacterial infection-induced immune response against breast implants.

8.
J Agric Food Chem ; 2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36701314

RESUMO

α-Arbutin is extensively used in cosmetic industries. The lack of highly active enzymes and the cytotoxicity of hydroquinone limit the biosynthesis of α-arbutin. In this study, a whole-cell biocatalytic approach based on enzyme engineering and engineered cell modification was identified as effective in enhancing α-arbutin production. First, a sucrose phosphorylase (SPase) mutant with higher enzyme activity was obtained by experimental screening. Next, to avoid the oxidation of hydroquinone, we established an anaerobic process to improve the robustness of the cells by knocking out lytC, sdpC, and skfA in Bacillus subtilis and overcoming the inhibitory effect of a high concentration of hydroquinone. Finally, the engineered strain was used for biotransformation in a 5 L fermenter with batch feeding for 24 h. The final yield of α-arbutin achieved was 129.6 g/L, which may provide a basis for the large-scale industrial production of α-arbutin.

9.
Artigo em Inglês | MEDLINE | ID: mdl-36613190

RESUMO

The influence of environmental quality on the quality of urban life and on migration decisions is an important research issue in urban economics and environmental economics. Using the 2012-2014 China Labor Dynamics Survey data (CLDS), this paper uses a conditional logit model (CLM) and Instrumental Variable (IV) estimation to examine the impact of air pollution on the migrant migration decision. We find that air pollution significantly negatively impacts the migration decisions of migrants. Specifically, if the PM2.5 level of a city increases by 10 µg/m3, the probability of migrants flowing into the city will be significantly reduced by 21.2%. It shows that migrants choose to flow into cities with better spatial quality to reduce the risk of exposure to air pollution. After controlling for the characteristics of the outflow and the reasons for the flow, the impact of air pollution on migrants' migration decisions remains robust. Heterogeneity analysis shows that middle-aged, male, married, and highly educated migrants are more sensitive to air pollution. This paper enriches the research on air pollution and labor mobility at the micro level and provides empirical evidence for policymaking related to environmental governance and labor mobility in a low-carbon society.


Assuntos
Poluição do Ar , Migrantes , Humanos , Pessoa de Meia-Idade , Masculino , Conservação dos Recursos Naturais , Política Ambiental , Emprego , China
10.
Foods ; 12(1)2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36613401

RESUMO

The antifungal effect of metabolites produced by a new strain of Lactiplantibacillus (Lpb.) plantarum LPP703, isolated from naturally fermented yak yogurt, was investigated. The results showed that Lpb. plantarum LPP703 significantly inhibited four fungal species, including Penicillium sp., Rhizopus delemar, Aspergillus flavus, and Aspergillus niger. The metabolites produced after 20 h of Lpb. plantarum LPP703 fermentation showed the highest antifungal activity against Penicillium sp. Compared with the control group, the Lpb. plantarum LPP703 metabolites-treated Penicillium sp. spores were stained red by propidium iodide, indicating that the cell membrane of the fungal spores was damaged. Moreover, the antifungal effect of the Lpb. plantarum LPP703 metabolites on Penicillium sp. was not changed after heating or treatment with various proteases, but showed a sharp decrease when the pH value was regulated to 5.0 or above. The oleamide, trans-cinnamic acid, and citric acid were the three most abundant in the Lpb. plantarum LPP703 metabolites. Molecular docking predicated that the oleamide interacted with the active site of lanosterol 14-alpha-demethylase (CYP51, a crucial enzyme for fungal membrane integrity) through hydrogen bonds and had the lowest docking score, representing the strongest binding affinity to CYP51. Taken together, the metabolites from a new strain of Lpb. plantarum, LPP703, had potent antifungal activity against Penicillium sp., which might be associated with the damage of the active ingredient to fungal membrane integrity. This study indicated that Lpb. plantarum LPP703 and its metabolites might act as biological control agents to prevent fungal growth in the food industry.

11.
Clin Lab ; 69(1)2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36649525

RESUMO

BACKGROUND: The prognosis of hepatocellular carcinoma (HCC) is closely related to the diagnostic stage. Due to the difficulty diagnosing early-stage HCC, most patients with HCC are diagnosed at the advanced stage. In this study, we used protein induced by vitamin K absence or antagonist-II (PIVKA-II) and alpha-fetoprotein (AFP) combined with aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin (T-Bil) to establish a novel diagnostic model for early-stage hepatitis B virus (HBV)-related HCC. METHODS: The serum levels of PIVKA-II, AFP, AST, ALT, and T-Bil were measured in 148 patients with early-stage HBV-related HCC and 940 patients with chronic hepatitis B. The receiver operating characteristic (ROC) curves were used to verify the diagnostic efficacy of the novel diagnostic model for early-stage HBV-related HCC. RESULTS: The mathematical model of [1.5 x PIVKA-II/(AST x T-Bil) + AFP/(ALT x T-Bil)] was selected as the novel diagnostic model. The areas under ROC curves (AUROCs) of the novel diagnostic model for detecting early-stage HBV-related HCC were significantly higher than those of PIVKA-II, AFP, and PIVKA-II combined with AFP (HCC ≤ 5 cm: 0.925 vs. 0.826, 0.666, and 0.821; HCC < 3 cm: 0.896 vs. 0.741, 0.651, and 0.765, respectively) (all p < 0.001). Using serum levels of AFP ≥ 20 ng/mL, the diagnostic model had the highest AUROC values of 0.960 and 0.933 for HCC ≤ 5 cm (89 cases) and HCC < 3 cm (40 cases), respectively, with a sensitivity of 83.15%, and 77.50% and specificity of 95.34% and 90.69%, respectively. CONCLUSIONS: The novel diagnostic model is superior to PIVKA-II and AFP for diagnosing early-stage HBV-related HCC, especially in patients with abnormal serum AFP levels.


Assuntos
Carcinoma Hepatocelular , Hepatite B , Neoplasias Hepáticas , Humanos , alfa-Fetoproteínas/metabolismo , Biomarcadores , Biomarcadores Tumorais , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/virologia , Vírus da Hepatite B , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/virologia , Protrombina , Curva ROC , Hepatite B/complicações
12.
Cell Discov ; 9(1): 8, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36658132

RESUMO

N6-methyldeoxyadenine (6mA) has recently been reported as a prevalent DNA modification in eukaryotes. The Tetrahymena thermophila MTA1 complex consisting of four subunits, namely MTA1, MTA9, p1, and p2, is the first identified eukaryotic 6mA methyltransferase (MTase) complex. Unlike the prokaryotic 6mA MTases which have been biochemically and structurally characterized, the operation mode of the MTA1 complex remains largely elusive. Here, we report the cryogenic electron microscopy structures of the quaternary MTA1 complex in S-adenosyl methionine (SAM)-bound (2.6 Å) and S-adenosyl homocysteine (SAH)-bound (2.8 Å) states. Using an AI-empowered integrative approach based on AlphaFold prediction and chemical cross-linking mass spectrometry, we further modeled a near-complete structure of the quaternary complex. Coupled with biochemical characterization, we revealed that MTA1 serves as the catalytic core, MTA1, MTA9, and p1 likely accommodate the substrate DNA, and p2 may facilitate the stabilization of MTA1. These results together offer insights into the molecular mechanism underpinning methylation by the MTA1 complex and the potential diversification of MTases for N6-adenine methylation.

13.
New Phytol ; 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36683448

RESUMO

Cyanobacterial blooms pose a serious threat to public health due to the presence of cyanotoxins. Microcystin-LR (MC-LR) produced by Microcystis aeruginosa is the most common cyanotoxins. Due to the limitation of isolation, purification, and genetic manipulation techniques, it is difficult to study and verify in situ the biosynthetic pathways and molecular mechanisms of MC-LR. We reassembled the biosynthetic gene cluster (mcy cluster) of MC-LR in vitro by synthetic biology, designed and constructed the strong bidirectional promoter biPpsbA2 , transformed it into Synechococcus 7942, and successfully expressed MC-LR at a level of 0.006-0.018 fg cell-1 day-1 . We found the expression of MC-LR led to abnormal cell division and the cellular filamentation, further using various methods proved that by irreversibly competing its GTP binding site, MC-LR inhibits assembly of the cell division protein FtsZ. The study represents the first reconstitution and expression of the mcy cluster and the autotrophic production of MC-LR in model cyanobacterium, which lays the foundation for resolving the microcystins (MCs) biosynthesis pathway. The discovered role of MC-LR in cell division reveals a mechanism of how blooming cyanobacteria gain a competitive edge over their non-blooming counterparts.

14.
Quant Imaging Med Surg ; 13(1): 471-488, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36620169

RESUMO

Background: The dorsal striatum, a nucleus in the basal ganglia, plays a key role in the execution of cognitive functions in the human brain. Recent studies have focused on how the dorsal striatum participates in a single cognitive function, whereas the specific roles of the caudate and putamen in performing multiple cognitive functions remain unclear. In this paper we conducted a meta-analysis of the relevant neuroimaging literature to understand the roles of subregions of the dorsal striatum in performing different functions. Methods: PubMed, Web of Science, and BrainMap Functional Database were searched to find original functional magnetic resonance imaging (fMRI) studies conducted on healthy adults under reward, memory, emotion, and decision-making tasks, and relevant screening criteria were formulated. Single task activation, contrast activation, and conjunction activation analyses were performed using the activation likelihood estimation (ALE) method for the coordinate-based meta-analysis to evaluate the differences and linkages. Results: In all, 112 studies were included in this meta-analysis. Analysis revealed that, of the 4 single activation tasks, reward, memory, and emotion tasks all activated the putamen more, whereas decision-making tasks activated the caudate body. Contrast analysis showed that the caudate body played an important role in the 2 cooperative activation tasks, but conjunction activation results found that more peaks appeared in the caudate head. Discussion: Different subregions of the caudate and putamen assume different roles in processing complex cognitive behaviors. Functional division of the dorsal striatum identified specific roles of 15 different subregions, reflecting differences and connections between the different subregions in performing different cognitive behaviors.

15.
Cell Res ; 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36627348

RESUMO

Only a small proportion of patients with triple-negative breast cancer benefit from immune checkpoint inhibitor (ICI) targeting PD-1/PD-L1 signaling in combination with chemotherapy. Here, we discovered that therapeutic response to ICI plus paclitaxel was associated with subcellular redistribution of PD-L1. In our immunotherapy cohort of ICI in combination with nab-paclitaxel, tumor samples from responders showed significant distribution of PD-L1 at mitochondria, while non-responders showed increased accumulation of PD-L1 on tumor cell membrane instead of mitochondria. Our results also revealed that the distribution pattern of PD-L1 was regulated by an ATAD3A-PINK1 axis. Mechanistically, PINK1 recruited PD-L1 to mitochondria for degradation via a mitophagy pathway. Importantly, paclitaxel increased ATAD3A expression to disrupt proteostasis of PD-L1 by restraining PINK1-dependent mitophagy. Clinically, patients with tumors exhibiting high expression of ATAD3A detected before the treatment with ICI in combination with paclitaxel had markedly shorter progression-free survival compared with those with ATAD3A-low tumors. Preclinical results further demonstrated that targeting ATAD3A reset a favorable antitumor immune microenvironment and increased the efficacy of combination therapy of ICI plus paclitaxel. In summary, our results indicate that ATAD3A serves not only as a resistant factor for the combination therapy of ICI plus paclitaxel through preventing PD-L1 mitochondrial distribution, but also as a promising target for increasing the therapeutic responses to chemoimmunotherapy.

16.
Neuromolecular Med ; 2023 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-36639554

RESUMO

Sleep deprivation causes significant memory impairment in healthy adults. Extensive research has focused on identifying the biological mechanisms underlying memory impairment. Microglia-mediated synaptic elimination plays an indispensable role in sleep deprivation. Here, the potential role of the CD33/TREM2 signaling pathway in modulating memory decline during chronic sleep restriction (CSR) was evaluated. In this study, adult male C57BL/6 mice were sleep-restricted using an automated sleep deprivation apparatus for 20 h per day for 7 days. The Y-maze test revealed that spontaneous alternation was significantly reduced in CSR mice compared with control mice. The percentage of exploratory preference for the novel object in CSR mice was significantly decreased compared with that in control mice. These memory deficits correlated with aberrant microglial activation and increased phagocytic ability. Moreover, in CSR mice, the CD33 protein level in hippocampal tissue was significantly downregulated, but the TREM2 protein level was increased. In BV2 microglial cells, downregulation of CD33 increased TREM2 expression and improved microglial phagocytosis. Then, the sialic ligand monosialo-ganglioside 1 (GM1, 20 mg/kg, i.p.) was administered to mice once a day during CSR. Our results further showed that GM1 activated CD33 and consequently disturbed TREM2-mediated microglial phagocytosis. Finally, GM1 reversed CSR-induced synaptic loss and memory impairment via the CD33/TREM2 signaling pathway in the CA1 region of the hippocampus. This study provides novel evidence that activating CD33 and/or inhibiting TREM2 activity represent potential therapies for sleep loss-induced memory deficits through the modulation of microglial phagocytosis.

17.
Artigo em Inglês | MEDLINE | ID: mdl-36636603

RESUMO

Atherosclerosis (AS) is an inflammatory disease, whose occurrence and development mechanism is related to a great number of inflammatory cytokines. ß-sitosterol (BS), a natural compound extracted from numerous vegetables and plant medicines, has been suggested to improve AS, but the underlying mechanism remains vague. This work focused on investigating how BS affected the lipopolysaccharide (LPS)-treated human umbilical vein endothelial cells (HUVECs) and further exploring the potential targets and mechanisms through network pharmacology (NP) and molecular docking (MD). According to in vitro experiments, LPS resulted in an increase in the expression of inflammatory cytokines like tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (Cox-2), and interleukin-6 (IL-6). Besides, secretion of IL-6, interleukin-1ß (IL-1ß), and TNF-α also increased in HUVECs, whereas BS decreased the expression and secretion of these cytokines. NP analysis revealed that the improvement effect of BS on AS was the result of its comprehensive actions targeting 99 targets and 42 pathways. In this network, MAPKs signaling pathway was the core pathway, whereas MAPK1, MAPK8, MAPK14, and NFKB1 were the hub targets. MD analysis also successfully validated the interactions between BS and these targets. Moreover, verification test results indicated that BS downregulated the abnormal expression and activation of MAPKs and NF-κB signaling pathways in LPS-treated cells, including p38, JNK, ERK, NF-κB, and IκB-α phosphorylation expressions. Furthermore, p65 nuclear translocation was also regulated by BS treatment. In conclusion, the BS-related mechanisms in treating AS are possibly associated with inflammatory response inhibition by regulating MAPKs and NF-κB signaling pathways.

18.
Sensors (Basel) ; 23(2)2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36679428

RESUMO

Due to the influence of the shooting environment and inherent image characteristics, there is a large amount of interference in the process of image stitching a geological borehole video. To accurately match the acquired image sequences in the inner part of a borehole, this paper presents a new method of stitching an unfolded borehole image, which uses the image generated from the video to construct a large-scale panorama. Firstly, the speeded-up robust feathers (SURF) algorithm is used to extract the image feature points and complete the rough matching. Then, the M-estimator sample consensus (MSAC) algorithm is introduced to remove the mismatched point pairs and obtain the homography matrix. Subsequently, we propose a local homography matrix offset optimization (LHOO) algorithm to obtain the optimal offset. Finally, the above process is cycled frame by frame, and the image sequence is continuously stitched to complete the construction of a cylindrical borehole panorama. The experimental results show that compared with those of the SIFT, Harris, ORB and SURF algorithms, the matching accuracy of our algorithm has been greatly improved. The final test is carried out on 225 consecutive video frames, and the panorama has a good visual effect, and the average time of each frame is 100 ms, which basically meets the requirements of the project.


Assuntos
Algoritmos , Processamento de Imagem Assistida por Computador , Animais , Processamento de Imagem Assistida por Computador/métodos
19.
JMIR Form Res ; 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36693149

RESUMO

BACKGROUND: Older adults are particularly at risk from infectious diseases, including serve complications, hospitalization, and death. OBJECTIVE: This study aimed to explore the drivers of vaccine hesitancy among older adults based on the 3Cs framework, where socioeconomic status and vaccination history played as roles of moderators. METHODS: A cross-sectional questionnaire survey was conducted in Jiangsu Province, China between June 1, 2021, and July 20, 2021. Older adults (above 60 years) were recruited using a stratified sampling method. Vaccine hesitancy was setting influenced by confidence, complacency, and convenience in the model. Socioeconomic status and vaccination history processed through the item parceling method were used to moderate associations between the 3Cs and hesitancy. Hierarchical regression analyses and structural equation modeling were used to test the validity of the new framework. We performed 5000 trials of bootstrapping to calculate the 95% confidence interval (CI) of the pathway's coefficients. RESULTS: A total of 1341 older adults (response rate: 87%) participated. The age was 71.3 ± 5.4 years old and 44.7% of participants were men. Confidence [b = 0.967, 95% CI: 0.759, 1.201, P = .002], convenience (b = 0.458, 95% CI: 0.333, 0.590, P = .002), and less complacency (b = 0.301, 95% CI: 0.187, 0.408, P = .002) were positively associated with less vaccine hesitancy. Socioeconomic status weakened the positive effect of low complacency (b = -0.065, P = .03) on low vaccine hesitancy. Coronavirus disease 2019 (COVID-19) vaccination history negatively moderated the positive association between confidence (b = -0.071, P = .02) and lower vaccine hesitancy. CONCLUSIONS: Our study identified that confidence was the more influential dimension in reducing vaccine hesitancy among older adults. COVID-19 vaccination history, as well as confidence, have a positive association with less vaccine hesitancy, and it could weaken the role of confidence in vaccine hesitancy. Socioeconomic status had a substitution relationship with less complacency, which suggested a competitive positive association between them on less vaccine hesitancy.

20.
Phytomedicine ; 109: 154562, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36610124

RESUMO

BACKGROUND: Fibroblast-like synoviocytes (FLSs) are essential for joint destruction in rheumatoid arthritis (RA). 6-Shogaol, a phenolic extract isolated from ginger, has been found to have potential benefits in the treatment of diverse inflammatory and immune disorders. However, the role of 6-shogaol in RA has yet to be explored. PURPOSE: To reveal the effect of 6-shogaol on RA FLSs and MH7A cells and to investigate the molecular mechanism of 6-shogao in RA. METHODS: We performed MTT, EdU, cell apoptosis, cell migration and invasion, RT-qPCR, western blot analysis, and immunofluorescence to elucidate the effect of 6-shogaol on the proliferation, apoptosis, and migration of RA FLSs and MH7A cells and revealed its modulation of the PI3K/AKT/NF-κB pathway. The in vivo therapeutic effect of 6-shogaol was verified in mice with collagen-induced arthritis (CIA). RESULTS: 6-Shogaol suppressed proliferation, migration, and invasion, and induced apoptosis in RA FLSs and MH7A cells. 6-Shogaol also reduced the production of TNF-α, IL-1ß, IL-6, IL-8, MMP-2, and MMP-9. Molecular analysis revealed that 6-shogaol inhibited the PI3K/AKT/NF-κB pathway by activating PPAR-γ. Treatment with 6-shogaol ameliorated joint destruction of mice with CIA. CONCLUSION: This study revealed that 6-shogaol inhibited proliferation, migration, invasion, cytokine, and MMPs production, and induced apoptosis in RA FLSs via the PI3K/AKT/NF-κB pathway, providing a new natural potential drug for future RA treatments.


Assuntos
Artrite Experimental , Artrite Reumatoide , Sinoviócitos , Animais , Camundongos , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proliferação de Células , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/metabolismo , Artrite Experimental/tratamento farmacológico , Fibroblastos , Apoptose , Células Cultivadas
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