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BACKGROUND: Pulmonary arterial hypertension (PAH) is a life-threatening chronic cardiopulmonary disease. However, there is a paucity of studies that reflect the available biomarkers from separate gene expression profiles in PAH. METHODS: The GSE131793 and GSE113439 datasets were combined for subsequent analyses, and batch effects were removed. Bioinformatic analysis was then performed to identify differentially expressed genes (DEGs). Weighted gene co-expression network analysis (WGCNA) and a protein-protein interaction (PPI) network analysis were then used to further filter the hub genes. Functional enrichment analysis of the intersection genes was performed using Gene Ontology (GO), Disease Ontology (DO), Kyoto encyclopedia of genes and genomes (KEGG) and gene set enrichment analysis (GSEA). The expression level and diagnostic value of hub gene expression in pulmonary arterial hypertension (PAH) patients were also analyzed in the validation datasets GSE53408 and GSE22356. In addition, target gene expression was validated in the lungs of a monocrotaline (MCT)-induced pulmonary hypertension (PH) rat model and in the serum of PAH patients. RESULTS: A total of 914 differentially expressed genes (DEGs) were identified, with 722 upregulated and 192 downregulated genes. The key module relevant to PAH was selected using WGCNA. By combining the DEGs and the key module of WGCNA, 807 genes were selected. Furthermore, protein-protein interaction (PPI) network analysis identified HSP90AA1, CD8A, HIF1A, CXCL8, EPRS1, POLR2B, TFRC, and PTGS2 as hub genes. The GSE53408 and GSE22356 datasets were used to evaluate the expression of TFRC, which also showed robust diagnostic value. According to GSEA enrichment analysis, PAH-relevant biological functions and pathways were enriched in patients with high TFRC levels. Furthermore, TFRC expression was found to be upregulated in the lung tissues of our experimental PH rat model compared to those of the controls, and the same conclusion was reached in the serum of the PAH patients. CONCLUSIONS: According to our bioinformatics analysis, the observed increase of TFRC in the lung tissue of human PAH patients, as indicated by transcriptomic data, is consistent with the alterations observed in PAH patients and rodent models. These data suggest that TFRC may serve as a potential biomarker for PAH.
Subject(s)
Computational Biology , Pulmonary Arterial Hypertension , Animals , Rats , Computational Biology/methods , Humans , Pulmonary Arterial Hypertension/genetics , Pulmonary Arterial Hypertension/diagnosis , Pulmonary Arterial Hypertension/metabolism , Male , Biomarkers/blood , Biomarkers/metabolism , Rats, Sprague-Dawley , Protein Interaction Maps/genetics , Gene Expression Profiling/methods , Databases, GeneticABSTRACT
Aquaculture is one of the fastest growing sectors in global food production, recognized as a significant contributor to poverty alleviation, food security, and income generation. However, the frequent occurrence of diseases caused by pathogen infections result in reduced yields and economic losses, posing a substantial constraint to the sustainable development of aquaculture. Here, our study identified that four catechol compounds, quercetin, luteolin, caffeic acid, and chlorogenic acid, exhibited potent antiparasitic effects against Ichthyophthirius multifiliis in both, in vitro and in vivo. The parasite is recognized as one of the most pathogenic to fish worldwide. Using a combination of in silico methods, the dipeptidyl peptidase (DPP) was identified as a critical target for catechol compounds. The two hydroxyl radicals of the catechol group were essential for its binding to and interacting with the DPP protein. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that catechol compounds disrupt pathways associated with the metabolism and growth of I. multifiliis, thereby exerting antiparasitic effects. Furthermore, these compounds attenuated the expression of proinflammatory cytokines in vivo in fish and promoted macrophage polarization toward M2 phenotype by inhibiting the STAT1 signaling pathway. The dual activity of catechol compounds, acting as both direct antiparasitic and anti-inflammatory agents in fish, offers a promising therapeutic approach for combating I. multifiliis infections in aquaculture.
Subject(s)
Catechols , Ciliophora Infections , Fish Diseases , Hymenostomatida , Animals , Fish Diseases/immunology , Fish Diseases/parasitology , Fish Diseases/prevention & control , Hymenostomatida/drug effects , Catechols/pharmacology , Ciliophora Infections/veterinary , Ciliophora Infections/immunology , Ciliophora Infections/parasitology , Ciliophora Infections/prevention & control , Antiparasitic Agents/pharmacologyABSTRACT
Background: With the rapid growth of global aging, frailty has become a serious public health burden, affecting the life quality of older adults. Depressive symptoms (depression hereafter) and sleep quality are associated with frailty, but the pathways in which sleep quality and depression affect frailty remain unclear. Method: This cross-sectional study included 1866 community-dwelling older adults. Demographic characteristics and health-related data of them was collected, and we also assessed frailty, depression, and sleep quality. Descriptive statistics were carried out and ordinal logistic regression analysis was used to identify the factors correlated with frailty. Spearman correlation analysis and mediation analysis were employed to assess associations between sleep quality, depression and frailty. Two-sided p < 0.05 was considered as significant. Results: The results showed that 4.1% older adults were frail and 31.0% were pre-frail. Ordinal logistic regression showed that age, consumptions of vegetables, exercise, sleep quality, depression, number of chronic diseases, chronic pain, and self-rated health were correlated with frailty. Spearman correlation analysis revealed that frailty was associated with depression and sleep quality. There was a mediation effect that sleep quality was a significant and positive predictor of frailty (total effect = 0.0545, 95% boot CI = 0.0449-0.0641), and depression was a mediator between sleep quality and frailty (mediation effect = 60.4%). Conclusion: Depression and poor sleep quality may be early indicators of frailty in older adults. Improving the sleep quality and psychological state of older adults can improve frailty, which is beneficial for healthy aging.
Subject(s)
Depression , Frailty , Sleep Quality , Humans , Cross-Sectional Studies , Male , Female , Aged , China/epidemiology , Depression/epidemiology , Aged, 80 and over , Frail Elderly/statistics & numerical data , Frail Elderly/psychology , Independent Living , Middle Aged , Surveys and QuestionnairesABSTRACT
Quercetin (QCT) has a variety of pharmacological effects, such as antioxidant, antibacterial, anticancer, anticardiovascular and antiaging effects. However, its poor water solubility, stability and bioavailability limit its applications. The special structure of cyclodextrins and their derivatives with a hydrophobic inner cavity and hydrophilic outer wall can load a variety of hydrophobic drugs of a suitable size and shape, thereby improving the stability and solubility of these molecules. In this study, an inclusion complex of quercetin and sulfobutylether-ß-cyclodextrin was prepared. It was characterized via FT-IR, UV, 1H NMR, XRD, DSC, and SEM analysis, which revealed the successful formation of the inclusion complex. In vitro biological activity estimations were carried out and the results indicated that the inclusion complex displayed higher antioxidative and antibacterial properties compared with free QCT. In addition, the mechanisms of inclusion were explored using 1H NMR analysis and docking calculations, thus providing a theoretical basis for obtaining an inclusion complex.
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PD-1/PD-L1 monoclonal antibodies exhibit promising therapeutic effectiveness in multiple cancers. However, developing a simple and efficient non-antibody treatment strategy using the PD-1/PD-L1 signaling pathway still remains challenging. In this study, we developed a flow cytometry assay to screen bioactive compounds with PD-L1 inhibitory activity. A total of 409 marine natural products were screened, and sokotrasterol sulfate (SKS) was found to efficiently suppress the IFN-γ-induced PD-L1 expression. SKS sensitizes the tumor cells to antigen-specific T-cell killing in the T cell-tumor cell coculture system. Mechanistically, SKS directly targeted Janus kinase (JAK) to inhibit the downstream activation of signal transducer and activator of transcription (STAT) and the subsequent transcription of PDL1. Our findings highlight the immunological role of SKS that may act as a basis for a potential immunotherapeutic agent.
Subject(s)
B7-H1 Antigen , Interferon-gamma , Janus Kinases , Interferon-gamma/pharmacology , Humans , Janus Kinases/metabolism , Sterols/pharmacology , Signal Transduction/drug effects , Molecular Structure , T-Lymphocytes/drug effects , T-Lymphocytes/metabolism , Cell Line, TumorABSTRACT
Sharp steering-braking at a high speed exposes sport utility vehicles with high gravity centers and narrow wheel tracks to the risks of tire locking, sideslip and rollover. To avoid these risks and ensure braking safety, yaw stability and roll stability upon steering-braking, a braking-yaw-roll stability integrated control strategy was proposed, which consists of a supervisor, an upper and a lower controller for the front and rear axle independent drive electric vehicle. In the supervisor, a nonlinear vehicle predictive model was constructed and four control modes were proposed according to the vehicle status and rollover indexes. The weight coefficients between braking force, yaw stability and roll stability are determined dynamically by the control mode and output to the upper controller. The upper controller used a nonlinear model predictive control to determine the longitudinal braking force distribution of the four wheels. And in the lower controller, the regenerative braking torque and friction braking torque of each wheel were distributed. Finally, simulation verifications were carried out on the high and low adhesion roads. The results show that the control strategy proposed in this study can effectively prevent the vehicle from rollover while ensuring braking safety and yaw stability.
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Background: There is limited real-world evidence on treatment patterns of patients with Crohn's disease (CD) initiating biologics with an extensive follow-up period. This study describes persistence and dose titration among CD patients with 3 years of follow-up. Methods: This retrospective observational study was conducted using the STATinMED RWD Insights all-payer medical and pharmacy data. Adult patients with at least 1 CD medical claim and at least 1 medical/pharmacy claim for a biologic (adalimumab [ADA], certolizumab pegol (CZP), infliximab [IFX] and its biosimilar products [IFX-BS], ustekinumab [UST], and vedolizumab [VDZ]) between September 2016 and October 2018 were identified. Commercially insured patients with continuous capture for at least 12 months before and at least 36 months after biologics initiation were selected. Confirmed CD patients were included in the final cohort. Baseline patient characteristics and treatment patterns over the 3-year follow-up period were evaluated. Results were summarized using means and SD or counts and percentages. Results: A total of 2309 confirmed patients with CD were identified (847 [36.7%] IFX, 534 [23.1%] ADA, 486 [21.1%] VDZ, 394 [17.1%] UST, 85 [3.7%] CZP, and 72 [3.1%] IFX-BS). CZP and IFX-BS were excluded due to small sample sizes. Approximately half of CD patients were between ages 35 and 54. Patients on UST had a higher Charlson Comorbidity Index score. Common comorbidities (>10%) included anemia, anxiety, depression, and hypertension. Persistence over 3 years' follow-up was highest for UST (61.4%) patients, followed by VDZ (58.0% ), ADA (52.1% , and IFX (48.1%). The discontinuation rate without switch or restart was highest for ADA (37.3%), followed by UST (30.7%), IFX (28.1%), and VDZ (25.3%). Over the 3 years of follow-up, the dose titration rate was highest for IFX (76.5%) and lowest for UST (50.8%). In particular, UST had the lowest dose escalation rate (35.5%) and highest dose-reduction rate (16.5%). Conclusions: Patients with CD on UST had the highest persistence and lowest dose escalation across different biologic users over the 3-year follow-up period, possibly suggesting a better clinical response of UST. Future studies with longer follow-up adjusting for confounders are needed to better understand treatment patterns among biologics users.
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BACKGROUND: Oxidation is a major problem for oils and fats, which can be mitigated by antioxidants. Rutin has excellent antioxidant activity, but its poor lipid solubility greatly limits its practical application. In this study, an efficient enzymatic synthesis route of lipophilic rutin ester was established using oleic acid as an acyl donor, and the antioxidant potential of rutin oleate was evaluated for the first time by proton (1 H) nuclear magnetic resonance (NMR) spectroscopy. RESULTS: The synthesized product was finally identified as rutin oleate by Fourier transform infrared, high-performance liquid chromatography-mass spectrometry, and 1 H, carbon-13, and DEPT-135 NMR analyses, and the acylation site was the 4â´-OH of the rhamnose group in the rutin molecule. The maximum conversion was over 93% after 48 h of reaction using Novozym 435 as catalyst under the best conditions among these tests. The conversion of rutin ester decreased with the increase of carbon chain length and the number of carbon-carbon double bonds of the fatty acid molecule. Most importantly, rutin oleate exhibited antioxidant capacity comparable to butylated hydroxytoluene and its counterparts (rutin and oleic acid) at low temperatures (60° C), but had a significant advantage at high temperatures (120° C). CONCLUSION: The antioxidant activity of rutin was significantly enhanced by lipase-mediated esterification with oleic acid. Therefore, rutin oleate could be further developed as a novel antioxidant for use in oil- and fat-based foods. © 2023 Society of Chemical Industry.
Subject(s)
Antioxidants , Rutin , Antioxidants/chemistry , Oleic Acid/chemistry , Lipase/chemistry , Carbon/chemistry , Esters , OilsABSTRACT
TiO2 has been considered as a promising intercalation lithium-ion-battery (LIB) anode material owing to its robust cyclability. However, it suffers from low capacity. Herein, we construct a sub 10 nm scale interfused TiO2/SiOx hybrid with a bicontinuous structure, in which bridged TiO2 nanoparticles (over 80 wt %) are densely packed within a wormlike SiOx network, through the simple oxidation of MAX Ti3SiC2 ceramic. State-of-the-art in situ microscopy characterization unravels a "mutual-stabilizing" effect from the interfused TiO2/SiOx hybrid upon lithiation. That is to say, the two interpenetrated active components restrain the volume expansion of each other with the stress being relieved through abundant interfaces. Meanwhile, the stress generated from one phase functioned as the compressive force on the other phase and vice versa, offsetting the overall volume effect and synergistically reinforcing the structure integrity. Benefiting from the "mutual-stabilizing" effect, the TiO2/SiOx composite manifests a high and stable specific capacity (â¼671 mAh g-1 after 580 cycles at 0.1 A g-1) with a low volume expansion of â¼14% even in an extended potential window of 0.01-3.0 V (vs Li+/Li). The concept of mutual-stabilizing effect, in principle, applies to a wide class of interfused bicontinuous hybrids, providing insight into the design of LIB anode materials with high capacity and longevity.
ABSTRACT
The study aimed to characterize phenolic compounds of the Inonotus sanghuang's ethyl-acetate fraction (EAF) and assess the neuroprotective effect of EAF using the H2O2-treated primary cortical neuronal cells (PCNC) model. Using HPLC-ECD, 5 phenolics were identified and quantified from EAF. H2O2-treated PCNC experiments in vitro showed that pretreatment with EAF increased the GSH-PX and SOD activities and reduced the NO, MDA, and Aß contents. Furthermore, EAF suppressed the production of IL-1ß, IFN-γ, IL-6, and TNF-α in H2O2-treated PCNC. Other mechanisms found that EAF reduced Bax, caspase 9, and caspase 3 expressions at the mRNA and protein levels while increasing Bcl-2 expression at the mRNA and protein levels. These results showed that EAF could serve as potential agents for anti-NDD. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-022-01107-x.
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BACKGROUND: Radiotherapy (RT) is a risk factor for impaired outcomes after implant-based immediate breast reconstruction (IBR). Large studies including long-term follow-up are relatively scarce. The purpose of this analysis was to assess long-term effects of RT in implant-based IBR, distinguishing between implant removal because of postoperative complications versus patient preference. METHODS: This population-based cohort study included all patients with breast cancer who underwent implant-based IBR in Stockholm between 2005 and 2015. Data were collected through national registers and medical charts. The main endpoint was implant removal owing to postoperative complications (wound breakdown, infection, bleeding) or patient preference (dissatisfaction, pain, capsular contracture), with or without conversion to autologous reconstruction. RESULTS: Some 1749 implant-based IBRs in 1687 women were included. Median follow-up was 72 (range 1-198) months. Reconstructions were divided according to receipt of RT: No RT (n = 856, 48.9 per cent), adjuvant RT (n = 749, 42.8 per cent), and previous RT (n = 144, 8.2 per cent). Implant removal occurred after 266 reconstructions (15.2 per cent); 68 (7.9 per cent) in the no RT, 158 (21.1 per cent) in the adjuvant RT, and 40 (27.8 per cent) in the previous RT group. Implant removal was because of postoperative complications in 152 instances (57.1 per cent) and was most common in the first 3 years. This was especially observed in the previous RT group, where 15 of 23 implant removals occurred during the first 6 months. Implant removal owing to patient preference (114 of 266, 42.9 per cent) became more common with increasing follow-up. CONCLUSION: Implant removal after implant-based IBR is significantly associated with RT. The reason for implant removal shifts over time from postoperative complications to patient preference.
Irradiation of the chest wall after breast removal and implant placement (reconstruction) increases the risk of complications. These may lead to removal of the implant. Some women then choose a new breast reconstruction without an implant. The aim of this project was to find out how much irradiation affects complications after breast reconstruction using implants. This work used information on women who had a breast reconstruction with implants in Stockholm, Sweden, from 2005 to 2015. The main focus was on removal of the implant. This could be due to complications or patient preference. Implant removal could be with or without a new breast reconstruction. Of 1749 reconstructed breasts in 1687 women, 266 implants were removed. This was most often because of a complication, especially in the first years after surgery, but nearly as often due to patient wish. Implant removal owing to patient wish occurred later. Irradiation was a major factor increasing the risk of implant removal, together with, for example, smoking and obesity.
Subject(s)
Breast Implants , Breast Neoplasms , Mammaplasty , Breast Neoplasms/radiotherapy , Breast Neoplasms/surgery , Cohort Studies , Female , Humans , Mastectomy , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Postoperative Complications/surgery , Radiotherapy, Adjuvant , Retrospective StudiesABSTRACT
Postpartum hemorrhage (PPH) is an obstetric emergency instigated by excessive blood loss which occurs frequently after the delivery. The PPH can result in volume depletion, hypovolemic shock, and anemia. This is particular condition is considered a major cause of maternal deaths around the globe. Presently, physicians utilize visual examination for calculating blood and fluid loss during delivery. Since the classical methods depend on expert knowledge and are inaccurate, automated machine learning based PPH diagnosis models are essential. In regard to this aspect, this study introduces an efficient oppositional binary crow search algorithm (OBCSA) with an optimal stacked auto encoder (OSAE) model, called OBCSA-OSAE for PPH prediction. The goal of the proposed OBCSA-OSAE technique is to detect and classify the presence or absence of PPH. The OBCSA-OSAE technique involves the design of OBCSA based feature selection (FS) methods to elect an optimum feature subset. Additionally, the OSAE based classification model is developed to include an effective parameter adjustment process utilizing Equilibrium Optimizer (EO). The performance validation of the OBCSA-OSAE technique is performed using the benchmark dataset. The experimental values pointed out the benefits of the OBCSA-OSAE approach in recent methods.
Subject(s)
Crows , Postpartum Hemorrhage , Shock , Algorithms , Animals , Female , Humans , Machine Learning , Postpartum Hemorrhage/diagnosis , Postpartum Hemorrhage/etiology , Pregnancy , Shock/complicationsABSTRACT
The purpose of this study was to investigate the effects of Lactobacillus rhamnosus GG (LGG) fermentation on the composition, structure, and functional properties of dietary fiber (DF) in bamboo shoot. Then, we added it to bread to evaluate the texture properties, digestive properties, and functionality of bread. After LGG fermentation, the DF was decomposed into pieces, which had stronger water-swelling capacity and nitrite adsorption capacity. The ability of producing short-chain fatty acids was significantly improved and the digestive resistance was remarkable enhanced as well. Except the bread hardness was increased, there was no significant difference in other texture properties when adding 3% FTDF-LGG to bread. It had good adsorption capacity of cholesterol and more than 25% reduced the release of reducing sugar. Overall, the technic of LGG fermentation had improved functional properties of DF in bamboo shoot, which could be applied to bread production for exerting its effects in the future. PRACTICAL APPLICATIONS: Bamboo shoots are immature and tender stems of bamboo, rich in nutritional value, and rich in DF. Bamboo shoot DF has been proven to have a variety of biological activities, and is the main material for bamboo shoot to exert functional activities. In this study, bamboo shoot DF was modified by LGG fermentation, which showed stronger functional activity, and was successfully applied to bread. This study lays the foundation for the fermented modified bamboo shoot DF and its application in food.
Subject(s)
Lacticaseibacillus rhamnosus , Bread , Dietary Fiber , Fermentation , VegetablesABSTRACT
Doxorubicin-induced cardiomyopathy (DCM) is a life-threatening event. The long noncoding RNAs (lncRNAs) have been reported with close associations with DCM, which may provide novel insight into pathophysiological mechanisms of DCM. DCM rat model and cell models were established using doxorubicin. Echocardiography analyses were performed to assess cardiac function. We found that testis developmental-related gene 1 (TDRG1) expression was upregulated in DCM rats and in doxorubicin-treated human umbilical vein endothelial cells (HUVECs). TDRG1 knockdown enhanced cell viability, promoted tube formation, and inhibited apoptosis of doxorubicin-treated HUVECs. Additionally, knockdown of TDRG1 alleviated cardiac injury in DCM rats. Mechanistically, miR-873-5p was identified to bind with TDRG1. In addition, protein kinase cAMP-dependent type II regulatory subunit alpha (PRKAR2) was confirmed to bind with miR-873-5p as a target mRNA. MiR-873-5p negatively regulated PRKAR2 mRNA and protein levels. At last, rescue assays indicated that the overexpression of PRKAR2 restored the effect of TDRG1 knockdown on doxorubicin-treated HUVEC angiogenesis and apoptosis. To conclude, TDRG1 aggravates DCM progression by binding with miR-873-5p to upregulate PRKAR2. This work suggested the potential of TDRG1 as a target for DCM treatment.
Subject(s)
Cardiomyopathies , MicroRNAs , RNA, Long Noncoding , Animals , Apoptosis/genetics , Cardiomyopathies/chemically induced , Cardiomyopathies/genetics , Doxorubicin , Human Umbilical Vein Endothelial Cells/metabolism , Humans , Male , MicroRNAs/genetics , MicroRNAs/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , RNA, Messenger , Rats , Testis/metabolismABSTRACT
Ischaemic stroke (IS) is a cerebrovascular disease caused by cerebral infarction and cerebral artery occlusion. In this study, we proposed that EVs from bone marrow stromal cells (BMSCs) could reduce the impact of stroke by reducing the resultant glial cell activation and blood-brain barrier (BBB) leak. We furthermore investigated some of the signalling mechanisms. The transient middle cerebral artery occlusion (t-MCAO) mouse model was established. The behavioural deficits and neuronal damage were verified using Bederson's scale and the 28-point neurological score. The area of cerebral infarction was detected. The expressions of astrocytes/microglia markers and BBB permeability were evaluated by 2,3,5-triphenyltetrazolium chloride (TTC) staining. The internalization of EVs by astrocytes/microglia in the peripheral area was detected by fluorescence labelling. The expressions of astrocyte/microglia markers were measured by RT-qPCR. Levels of TNF-α and IL-1ß in microglia were detected by ELISA. BBB permeability was evaluated. The downstream target genes and pathway of miR-124 were analysed. Microglia/astrocytes were treated by oxygen-glucose deprivation reoxygenation (OGD/R). OGD/R microglia/astrocyte conditioned medium was used to culture bEnd.3 cells. The transendothelial electric resistance (TEER) of bEnd.3 cells was measured, and BBB permeability was characterized. Our results suggested that EVs from BMSCs can indeed reduce the extent of stroke-mediated damage and evidenced that these effects are mediated via expression of the non-coding RNA, miR-124 that may act via the peroxiredoxin 1 (PRX1). Our results provided further motivation to pursue the use of modified EVs as a treatment option for neurological diseases.
Subject(s)
Brain Ischemia , Extracellular Vesicles , Mesenchymal Stem Cells , MicroRNAs , Peroxiredoxins , Stroke , Animals , Astrocytes/metabolism , Blood-Brain Barrier/metabolism , Brain Ischemia/metabolism , Endothelial Cells/metabolism , Extracellular Vesicles/metabolism , Glucose/metabolism , Homeodomain Proteins , Infarction, Middle Cerebral Artery/metabolism , Mesenchymal Stem Cells/metabolism , Mice , MicroRNAs/genetics , MicroRNAs/metabolism , Oxygen/metabolism , Permeability , Peroxiredoxins/metabolism , Stroke/metabolismABSTRACT
BACKGROUND: Coronary atherosclerosis (AS) is characterized by the formation of plaque in the vessel wall. The structural and functional changes of vascular smooth muscle cells (VSMCs) can promote plaque formation and induce plaque instability. OBJECTIVE: To investigate the functions and mechanism of miR-222-5p in VSMCs under the treatment of oxidized low-density lipoprotein (ox-LDL). METHODS: miR-222-5p expression in ox-LDL-treated VSMCs and the serum of Apolipoprotein E (ApoE) knockout mice was detected by reverse transcription quantitative polymerase chain reaction. The viability and migration of VSMCs were detected by Cell Counting Kit-8 and Transwell assays. Protein levels of proliferation and migration-related factors were evaluated by western blotting. Luciferase reporter assays were performed to explore the binding between miR-222-5p and retinoblastoma susceptibility protein (RB1) gene in VSMCs. ApoE-knockout mice were infected with the lentivirus inhibiting miR-222-5p expression to explore the effect of miR-222-5p on pathological changes. Hematoxylin and eosin (H&E) staining, trichrome staining, and Oil Red O staining were conducted to determine the necrotic core area and atherosclerotic lesion size in the ascending aorta of ApoE-knockout mice. RESULTS: With the accumulation of ox-LDL concentration and treatment time, miR-222-5p expression was gradually upregulated in VSMCs. Similarly, miR-222-5p expression was increased in the serum of ApoE-knockout mice. miR-222-5p knockdown inhibited the proliferative and migratory abilities of ox-LDL-treated VSMCs, and the inhibitory effect on cellular behaviors was then significantly reversed by co-knockdown of RB1. RB1 is a downstream target gene of miR-222-5p, and miR-222-5p bound with 3'-untranslated region of RB1 in VSMCs. We further confirmed that miR-222-5p knockdown alleviated pathological changes and inhibited lipid deposition in the serum of ApoE-knockout mice in vivo. CONCLUSION: miR-222-5p accelerates the dysfunction of VSMCs and promotes pathological changes and lipid deposition in ApoE-knockout mice by targeting RB1. The study may provide novel therapeutic targets for AS.
Subject(s)
MicroRNAs , Muscle, Smooth, Vascular , Retinoblastoma Binding Proteins , Animals , Cell Movement , Cell Proliferation , Humans , Mice , MicroRNAs/genetics , MicroRNAs/physiology , Muscle, Smooth, Vascular/physiopathology , Retinoblastoma Binding Proteins/genetics , Retinoblastoma Binding Proteins/metabolism , Signal Transduction , Ubiquitin-Protein Ligases/metabolismABSTRACT
Human societies develop rapidly through the advancement of technology; however, with these advancements, many problems are emerging. The topic chosen for this study surrounds the e-waste, which has become a major problem around the world. Second-hand and unused mobile phones are a big part of globally generated e-waste. If these devices are properly recycled, they can generate substantial economic and resource value. Yet if they are indiscriminately discarded, they cause a profound environmental impact. Given the current low recovery rate of mobile phones, an increase in recovery rates becomes critical in lessening economic and environmental impacts. Based on the status quo of second-hand mobile phone recycling processes in China, this article analyzes the behavior of individuals and recyclers through a comprehensive static information game theory and finds ways to increase the recycling rate of second-hand mobile phones. The study helps the customers, to clearly identify the recycle price. In case of market, the government policy can be introduced with a reward and punishment mechanism. Furthermore, under the ideological guidance of game theory, this paper also establishes a corresponding price model of second-hand mobile phone recycling based on best response dynamics like search, variable neighborhood search, and hybrid meta-heuristic method. This model shows that the recovery time differences have a significant impact on the recovery price. Moreover, to an extent, this model can promote the possibility and initiative of customers choosing cell phone recycling.
Subject(s)
Cell Phone , Game Theory , Recycling , China , Humans , Recycling/methods , TechnologyABSTRACT
OBJECTIVE: Myocardial ischemia-reperfusion (I/R) injury (MIRI) refers to the more serious myocardial injury after blood flow recovery, which seriously affects the prognosis of patients with ischemic cardiomyopathy. This study explored the new targets for MIRI treatment by investigating the effects of miR-190-5p and its downstream target on the structure and function of myocardial cells. METHODS: We injected agomir miR-190-5p into the tail vein of rats to increase the expression of miR-190-5p in rat myocardial cells and made an I/R rat model by coronary artery occlusion. We used 2,3,5-triphenyl tetrazolium chloride staining, lactate dehydrogenase (LDH) detection, echocardiography, and hematoxylin-eosin (HE) staining to determine the degree of myocardial injury in I/R rats. In addition, we detected the expression of inflammatory factors and apoptosis-related molecules in rat serum and myocardial tissue to determine the level of inflammation and apoptosis in rat myocardium. Finally, we determined the downstream target of miR-190-5p by Targetscan system and dual luciferase reporter assay. RESULTS: The expression of miR-190-5p in an I/R rat myocardium was significantly lower than that in normal rats. After treatment of I/R rats with agomir miR-190-5p, the ischemic area of rat myocardium and the concentration of LDH decreased. The results of echocardiography and HE staining also found that overexpression of miR-190-5p improved the structure and function of rat myocardium. miR-190-5p was also found to improve the viability of H9c2 cells in vitro and reduce the level of apoptosis of H9c2 cells. The results of Targetscan system and dual luciferase reporter assay found that miR-190-5p targeted to inhibit pleckstrin homology domain leucine-rich repeat protein phosphatase 1 (PHLPP1). In addition, inhibition of PHLPP1 was found to improve the viability of H9c2 cells. CONCLUSION: Therefore, miR-190-5p can reduce the inflammation and apoptosis of myocardium by targeting PHLPP1, thereby alleviating MIRI.
Subject(s)
MicroRNAs/physiology , Myocardial Reperfusion Injury/prevention & control , Nuclear Proteins/physiology , Animals , Apoptosis , Cell Line , Disease Models, Animal , Echocardiography , Inflammation Mediators/metabolism , L-Lactate Dehydrogenase/metabolism , Male , Myocardial Reperfusion Injury/metabolism , Myocardial Reperfusion Injury/physiopathology , Myocardium/metabolism , Myocardium/pathology , Rats , Rats, Sprague-DawleyABSTRACT
BACKGROUND: Current evidence for the effects of radiotherapy (RT) on implant-based immediate breast reconstruction (IBR) is limited by short follow-up and lack of patient-reported outcomes (PROs). It is central to integrate long-term comprehensive outcome data into the preoperative decision-making process. The aim of the present study was to determine long-term surgical outcomes and PROs in relation to RT after implant-based IBR. METHODS: This was a longitudinal cohort study of PRO data obtained in surveys conducted in 2012 and 2020 using the BREAST-Q questionnaire. All women undergoing therapeutic mastectomy and implant-based IBR between 1 January 2007 and 31 December 2011 at four breast centres in Stockholm, Sweden, were identified. The endpoint was implant removal owing to surgical complications or patient preference. RESULTS: Median follow-up was 120 (range 1-171) months. After 754 IBRs in 729 women, implant removal occurred in 128 (17 per cent): 34 of 386 (8.8 per cent) in the no-RT group, 20 of 64 (31.3 per cent) in the group with previous RT, and 74 of 304 (24.3 per cent) in the postoperative RT group (P < 0.001). Implant removal was because of surgical complications in 60 instances (7.9 per cent), and patient preference in 68 (9.0 per cent). The BREAST-Q response rate was 72.2 per cent. Women with previous RT scored lower than those without RT on all scales, apart from psychosocial well-being. Women with postoperative RT scored lower only on physical well-being. No scores in the two RT groups had deteriorated between the survey time points, whereas satisfaction with breasts and overall outcome had decreased in the no-RT group. CONCLUSION: Although RT was significantly associated with higher implant removal rates, PROs remained stable over 8 years despite irradiation.
Current evidence for the effects of radiotherapy (RT) on implant-based immediate breast reconstruction (IBR) is limited by short follow-up. The aim was to determine surgical outcomes and patient-reported outcomes (PROs) in relation to RT up to 13 years after implant-based IBR. After 754 implant-based breast reconstructions in 729 women in Stockholm, Sweden, implant removal was more common in irradiated than non-irradiated patients (P < 0.001). The response rate to the BREAST-Q questionnaire was 72.2 per cent. Women with previous RT scored lower than those without RT on all scales apart from psychosocial well-being. Women who had postoperative RT scored lower only on physical well-being. Although RT was significantly associated with higher implant removal rates, PROs remained stable despite irradiation.
Subject(s)
Breast Implants , Breast Neoplasms/therapy , Mammaplasty , Tissue Expansion Devices , Adult , Aged , Cohort Studies , Device Removal , Humans , Longitudinal Studies , Middle Aged , Patient Preference , Patient Reported Outcome Measures , Radiotherapy, AdjuvantABSTRACT
In this paper, a fast rotary mechanical projector (RMP) is designed and manufactured for high-speed 3D shape measurement. Compared with the common high-speed projectors, RMP has a good performance in high-speed projection, which can obtain high quality projected fringes with shorter camera exposure time by using the error diffusion binary coding method and chrome plating technology. The magnitude, acceptability of systemic projection error is analyzed and quantified in detail. For the quantified error, the probability distribution function (PDF) algorithm is introduced to correct the error. Corrected projection error is reduced to more than one third of the original error. Subsequently, a monocular measurement system composed of the RMP and a single camera is constructed. The combination of the RMP device and PDF algorithm ensure the accuracy of a corresponding 3D shape measurement system. Experiments have demonstrated that the proposed solution has a good performance for the 3D measurement of high-speed scenes.