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1.
Oxid Med Cell Longev ; 2022: 3412032, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35035658

RESUMO

The pathogenesis of diabetic retinopathy (DR) is complicated, and there is no effective drug. Oxidative stress-induced human retinal microvascular endothelial cells (HRMECs) injury is one of the pathogenic factors for DR. Molecular switches are considered high-risk targets in disease progression. Identification of molecular switch is crucial to interpret the pathogenesis of disease and screen effective ingredients. In this study, a systematic process was executed to discover therapeutic candidates for DR based on HRMECs injury. First of all, the molecular mechanism of HRMECs oxidative stress injury was revealed by transcriptomics and network pharmacology. We found that oxidative stress was one of the pivotal pathogenic factors, which interfered with vascular system development, inflammation, cell adhesion, and cytoskeleton damaged HRMECs through crosstalk. Then, network topology analysis was used to recognize molecular switches. The results indicated that the Keap1-Nrf2-ARE signaling pathway was the molecular switch in HRMECs oxidative stress injury. On this basis, the HEK293-ARE overexpression cell line was applied to obtain 18 active traditional Chinese medicine (TCM) ingredients. Furthermore, andrographolide, one of the 18 candidates, was applied in the HRMECs oxidative stress model to evaluate the accuracy of the systematic process. The efficacy evaluation results showed that andrographolide could regulate oxidative stress, vascular system development, inflammation, adhesion, and skeleton tissue to inhibit HRMECs injury cooperatively. And its mechanism was related to the Nrf2 signaling pathway. Overall, our data suggest that the Nrf2 signaling pathway is the molecular switch in the HRMECs oxidative stress injury. 18 potential Nrf2 agonists are likely to be promising DR candidates.

2.
J Healthc Eng ; 2022: 2373580, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35035814

RESUMO

Circular RNA LDLRAD3 behaved as an oncogene in several malignancies, but its effects in NSCLC and the involvement of downstream molecules and activation of signaling pathways had not been fully reported. We planned to explore how LDLRAD3 facilitated the malignancy of NSCLC. QRT-PCR was performed to evaluate the expression levels of LDLRAD3, miR-20a-5p, and SLC7A5 in NSCLC tissues and cells. si-LDLRAD3 was transfected to A549 and H1299 cells to knock down intrinsic LDLRAD3 to determine its oncogenic roles. CCK-8 assay and transwell assay were executed to assess cell proliferative, migrative, and invasive abilities. Dual-luciferase reporter (DLR) assay was manipulated to verify the ENCORI-predicted relationships between LDLRAD3 and miR-20a-5p and between miR-20a-5p and SLC7A5. Western blot, immunofluorescent assay, and immunohistochemistry were applied to explore the expression levels of SLC7A5, and the levels of mTORC1 pathway-related proteins were evaluated using western blot. Rescue experiments were conducted by transfecting si-LDLRAD3, miR-20a-5p inhibitor, and si-SLC7A5 to explore the influence of the LDLRAD3-miR-20a-5p-SLC7A5 axis on the malignant behaviors of NSCLC cells. The expression levels of LDLRAD3 and SLC7A5 were boosted, whereas miR-20a-5p was impeded in NSCLC tissues and cell lines. Knockdown of LDLRAD3 weakened the proliferation, migration, and invasion of A549 and H1299 cells. LDLRAD3 was verified to sponge miR-20a-5p and miR-20a-5p targeted SLC7A5. LDLRAD3 activated the mTORC1 singling pathway via the miR-20a-5p-SLC7A5 axis to strengthen the malignant properties of A549 and H1299 cells. We concluded that LDLRAD3 exerted oncogenic effects via the miR-20a-5p-SLC7A5 axis to activate the mTORC1 signaling pathway in NSCLC. Our findings enlightened that LDLRAD3 could become a potential therapeutic target in the treatment and management of NSCLC.

3.
Reprod Sci ; 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-34981457

RESUMO

The cause of endometriosis, which is characterized by the existence of functional endometrial tissue outside the uterine cavity, is poorly understood. Seminal plasma (SP) is rich in multiple cytokines that may promote endometrial tissue survival. Here, we evaluated the effect of SP on growth of endometrial mesenchymal stem cells (MSCs) from women with endometriosis (E-MSCs) and women without endometriosis (NE-MSCs). Proliferation, cell foci formation, cell cycle progression, and growth marker expression of E- and NE-MSCs were promoted by SP. These effects may be mediated through activation of transforming growth factor beta 1 (TGF-ß1), Akt, and p42/44 signaling, which enhances CDK2 and CDK6 expression and accelerates cell cycle progression. Xenografts exposed to SP exhibited a three-fold increase in volume and four-fold increase in weight after 14 days. Our findings demonstrate that TGF-ß1 in SP may promote endometrial tissue survival which will allow us to understand the pathogenesis and develop novel approaches for prevention and therapies of endometriosis.

4.
Sci Total Environ ; 803: 150027, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-34482139

RESUMO

This study aims to evaluate the ecotoxicity effects of single tetracycline (TC) exposure and mixture exposure in presence of polystyrene nanoplastics (PS-NPs, 80 nm) on juvenile Ctenopharyngodon idella. We carried out single and combined exposure of TC (5000 µg/L) and PS-NPs (20, 200, 2000 µg/L) for 7 days. Compared to TC single exposure, co-exposure to PS-NPs and TC significantly changed the levels of antioxidant entities, including T-AOC, SOD, and CAT in the liver and intestine of C. idella, indicating that PS-NPs might enhance the oxidative damage caused by TC. Further, the co-exposure significantly upregulated the mRNA expression levels of MMP2, MMP9, and IL-8 in a concentration-dependent manner in the liver and intestine tissues of C. idella, compared to the control and TC single exposure groups. Moreover, the phylogenetic tree showed that MMP2 and MMP9 in C. idella are relatively conservative, and the mRNA expressions of MMP2 are significantly positively correlated with TGFß1, IL8, and MMP9 in Liver hepatocellular carcinoma (LIHC) and Colon adenocarcinoma (COAD). The above genes in LIHC and COAD were significantly correlated with various immune cells. Further, histopathological analysis revealed tissue lesions in the intestine and gill of fish in all the exposed groups, compared to the control group. In short, the present study illustrated that the toxicological effects of organic pollutants such as TC could be influenced by the presence of NPs in the C. idella.


Assuntos
Carpas , Doenças dos Peixes , Ração Animal/análise , Animais , Dieta , Proteínas de Peixes/genética , Microplásticos , Filogenia , Poliestirenos/toxicidade , Tetraciclina
5.
Sci Total Environ ; 804: 150015, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34509843

RESUMO

Our previous studies showed hydrophobic organic compounds (HOCs) in the sediments of drinking water reservoirs caused DNA damage in human cells (Caco-2) after chlorination. However, the main mechanisms remained unclear. This study compared oxidative damage and EROD activity in Caco-2 cells upon exposure to chlorinated HOCs, and the role of antioxidants (catalase, vitamin C and epigallocatechin gallate (EGCG)) in reducing the toxicities was examined. The result showed that chlorinated HOCs induced a 4-fold increase in production of reactive oxygen species (ROS) compared with HOCs. Antioxidants supplement significantly reduced ROS yields and DNA peroxidation. HOCs with relatively higher TEQbio were greatly reduced (about 98%) after chlorination, indicating dioxin-like toxicity is not the main factor inducing oxidative damage by chlorinated HOCs. Yet, ROS and the associated oxidative damage seem to be more responsible for causing DNA damage in the cells. Antioxidants including catalase, Vitamin C and EGCG showed protective effect against chlorination.


Assuntos
Água Potável , Antioxidantes , Células CACO-2 , Citocromo P-450 CYP1A1 , Humanos , Estresse Oxidativo , Espécies Reativas de Oxigênio
6.
Int J Gynaecol Obstet ; 156(1): 89-94, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33483955

RESUMO

OBJECTIVE: To investigate the factors influencing placenta accreta in pregnant women who previously underwent hysteroscopic adhesiolysis (HA). METHODS: This retrospective study enrolled 265 women with intrauterine adhesions (IUAs) at the Sir Run Run Shaw Hospital from January 2014 to December 2018. We followed up their pregnancy outcomes and maternal complications. RESULTS: The menstrual pattern and gestational history before operation were significantly different between the live birth and pregnancy loss groups. The age, extent of cavity involved, type of adhesions, times of adhesiolysis performed, and time interval from surgery to pregnancy were not significantly different between these two groups. In the third trimester, 48 of 140 patients had 53 perinatal complications, including placenta accreta (27), gestational diabetes mellitus (10), pregnancy-induced hypertension (6), postpartum hemorrhage (4), intrahepatic cholestasis of pregnancy (2), placenta previa (1), oligohydramnios (1), and intrauterine growth restriction (1). Logistic regression analysis showed that extent of cavity involved and times of adhesiolysis performed were associated with placenta accreta. CONCLUSION: The extent of cavity involved and times of adhesive separation surgeries were risk factors for placenta accreta in patients. The menstrual model and gestational history may provide the main predictive factors for pregnancy loss.


Assuntos
Ginatresia , Placenta Acreta , Doenças Uterinas , Feminino , Ginatresia/etiologia , Ginatresia/cirurgia , Humanos , Histeroscopia , Placenta Acreta/cirurgia , Gravidez , Estudos Retrospectivos , Fatores de Risco
7.
Front Aging Neurosci ; 13: 743193, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34867276

RESUMO

Objectives: This study aimed to identify the independent factors associated with depression in community-dwelling older adults in Wuhan, China. Methods: Four hundred and seventy older adults (aged ≥65 years) from four communities dwelling on Junshan Street in Wuhan, China were included in this study. Participants completed a questionnaire that asked questions pertaining to age, gender, educational level, income, living situation, care situation, social support, and social engagement. The 30-item Geriatric Depression Scale (GDS-30), the Fried frailty phenotype scale, the activities of daily living (ADL) scale, the mini nutritional assessment scale-short form (MNA-SF), and the Mini-cog scale were used to assess depression, frailty, self-care ability, malnutritional risk, and cognitive dysfunction, respectively. Differences in age, gender, educational level, income, living situation, care situation, social support, social engagement, ADL score, risk of malnutrition, frailty, and cognitive dysfunction between the non-depression (GDS-30 score <10 points) and depression groups (GDS-30 score ≥10 points) were compared using a chi-square test. Moreover, correlations between factors and depression were analyzed using Pearson's correlation. Then, significant variables (p < 0.05) from the chi-square test were included in a multivariable logistic regression model to identify the independent factors associated with depression. Results: The incidence of depression among the participants was 14.04%. Age (p < 0.001), educational level (p < 0.001), living situation (p < 0.001), social support (p = 0.001), ADL score (p = 0.023), frailty (p < 0.001), and cognitive dysfunction (p < 0.001) were all significantly associated with depression, in which age, poor social support, frailty, and cognitive dysfunction were identified as independent factors. Conclusion: Improving social support and effective interventions for frailty and cognitive dysfunction may help relieve depression in community-dwelling older adults.

8.
Front Oncol ; 11: 767957, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34868995

RESUMO

Microsatellite instability-high (MSI-H) is widely believed to be a biomarker for immune checkpoint inhibitors (ICIs) such as pembrolizumab in solid tumors. However, due to the low prevalence of MSI-H in most cancers, it tends to be insufficient to identify whether patients should receive ICIs according to this biomarker alone. Here, we report a Chinese esophageal squamous cell carcinoma (ESCC) patient with unusual divergent MSI status between the primary lesion (MSS) and metastatic lesion (MSI-H) which developed after platinum-based therapy and radiotherapy. Both his primary and metastatic tumors responded well to pembrolizumab-containing therapies or pembrolizumab monotherapy and maintained a complete response for over 24 months. Whole-exome sequencing and multiplex immunohistochemistry were used to examine his tissue specimens. Notably, there were multiple high-frequency mutations of DDR (DNA damage repair) genes shared in the primary lesion and metastatic lesion, especially in the latter. Besides, we observed considerable degrees of infiltrating CD3+/CD8+ lymphocytes in both of his primary tumor and metastatic tumor without obvious difference, suggesting that the conversion of microsatellite status had little effect on the infiltration of lymphocytes. Collectively, given the predictive role of DDR alterations for ICIs in other malignancies, the alterations of DDR genes might also be promising biomarkers in ESCC individuals receiving ICIs.

9.
Zhongguo Zhong Yao Za Zhi ; 46(23): 6243-6250, 2021 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-34951251

RESUMO

As a classic prescription for promoting blood circulation to remove blood stasis, Xuefu Zhuyu Decoction(XFZYD) is widely used in clinical practice and has notable curative effect. Based on the key targets of activating blood circulation, this study identified the active components of XFZYD to reveal the material basis. The components of XFZYD were collected from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The molecular docking models were built for the blood-activating targets obtained from the previous study with the components of XFZYD. The top five active components with measurability for each target were selected as the potential blood-activating components in the prescription. The efficacy of the prescription can embody key pharmacological and high-content components. In this study, anti-platelet aggregation activity was used to characterize the effect of activating blood, and the in vivo experiments were conducted to verify the accuracy of the active components. A total of 210 chemical components of XFZYD were screened out from TCMSP and docked with the key targets with the function of activating blood. Ligustrazine, acteoside, naringin, etc. were selected as the potential active components for activating blood in XFZYD. The anti-platelet aggregation activity of the combination of Chuanxiong Rhizoma, Rehmanniae Radix, Aurantii Fructus, Glycyrrhizae Radix et Rhizoma, and Carthami Flos was 9.82%±5.11%. Compared with that in the control group, the platelet aggregation induced by adenosine diphosphate(ADP) was significantly inhibited in the test group(P<0.01), which verified the accuracy of the active components. This study can guide the research on the material basis of XFZYD and provide insights into the development and utilization of the classical prescription.


Assuntos
Medicamentos de Ervas Chinesas , Medicamentos de Ervas Chinesas/farmacologia , Medicina Tradicional Chinesa , Simulação de Acoplamento Molecular , Rizoma
10.
J Tradit Chin Med ; 41(6): 959-967, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34939393

RESUMO

OBJECTIVE: To explore the molecular mechanism of warming moxibustion (WM) in knee osteoarthritis (KOA). METHODS: The knee joints of 40 New Zealand rabbits were placed in a plaster cast in an extended position to establish a KOA model. The animals were randomly divided into four groups: the control group, model group, WM group, and diclofenac (DF) group. Hematoxylin-eosin staining and the modified Mankin score were applied to evaluate the histopathological changes. Chondrocyte apoptosis was determined by the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Western blotting and real-time quantitative polymerase chain reaction were performed to measure the expression of interleukin-1α (IL-1ß), prostaglandin E receptor 3 (PTGER3), a disintegrin-like and metalloproteinase with thrombospondin type-1 motifs-5 (ADAMTS-5), matrix metalloproteinase-13 (MMP-13), and C-terminal telopeptides of collagen type II (CTX-II) in cartilage tissues of the different groups. The concentrations of IL-1ß, PTGER3, and CTX-II in serum were detected by the enzyme-linked immunosorbent assay. RESULTS: Rabbits with KOA in the WM and DF groups showed significantly reduced cartilage erosion and Mankin scores, compared with the untreated rabbits. The number of TUNEL-positive cells observed in the WM group was much fewer than that in the model group. The expression of PTGER3, MMP-13, CTX-II IL-1ß, and ADAMTS-5 in cartilage tissues was remarkably downregulated following therapy with WM and DF. Moreover, a marked reduction was observed in the serum levels of IL-1ß, PTGER3, and CTX-II in the WM and DF groups. CONCLUSION: WM exerts favorable therapeutic effects on articular injuries of KOA by regulating the expression of inflammatory and cartilage degradation-related cytokines.

11.
Zhongguo Zhong Yao Za Zhi ; 46(19): 4969-4977, 2021 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-34738391

RESUMO

The high shear wet granulation(HSWG) process of Chinese medicine has a complicated mechanism. There are many influencing factors that contribute to this process. In order to summarize the manufacturability of different kinds of materials in HSWG, this paper constructed a material library composed of 11 materials, including 4 Chinese medicine extracts and 7 pharmaceutical excipients. Each material was described by 22 physical parameters. Several binders were employed, and their density, viscosity and surface tension were characterized. Combining empirical constraints and the principle of randomization, 21 designed experiments and 8 verification experiments were arranged. The partial least squares(PLS) algorithm was used to establish a process model in prediction of the median granule size based on properties of raw materials and binders, and process parameters. The surface tension and density of binders, as well as the maximum pore saturation were identified as key variables. In the latent variable space of the HSWG process model, all materials could be divided into three categories, namely the Chinese medicine extracts, the diluents and the disintegrants. The granulation of Chinese medicine extracts required low viscosity and low amount of binder, and the resulted granule sizes were small. The diluent powders occupied a large physical space, and could be made into granules with different granule sizes by adjusting the properties of binders. The disintegrants tended to be made into large granules under the condition of aqueous binder. The combination use of material database and multivariate modeling method is conducive to innovate the knowledge discovery of the wet granulation process of Chinese medicine, and provides a basis for the formulation and process design based on material attributes.


Assuntos
Excipientes , Medicina Tradicional Chinesa , Composição de Medicamentos , Tamanho da Partícula , Pós , Comprimidos , Tecnologia Farmacêutica
12.
J Sep Sci ; 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34845820

RESUMO

In recent years, natural deep eutectic solvents have been favored greatly due to their environment friendly, mild biological toxicity and simple biodegradability. NADESs gradually applied for the extracting bioactive compounds from natural products efficiently. In this study, 20 natural deep eutectic solvents were prepared and their physical and chemical properties were tested. The ultrasonic-assisted extraction method was used to extract flavonoids from Trollius ledebouri and HPLC-UV was applied to examine two main bioactive flavonoids (orientin and vitexin). Compared with traditional solvents (water and 60% ethanol solution), natural deep eutectic solvents composed by L(-)-proline and levulinic acid (molar ratio 1:2) shows a super extraction efficiency. On this basis, the response surface method was used to optimize the extraction temperature, extraction time, water contents and solid-liquid ratio. As a consequence, the extraction temperature 60℃, extraction time 18 min, water content 14% (v/v) and the solid-liquid ratio 48 mL⋅g-1 were chose as the best extraction process. This study shows that natural deep eutectic solvents can effectively extract flavonoids from Trollius ledebouri, laying a foundation for the further application of natural deep eutectic solvents to extract bioactive compounds from natural products. This article is protected by copyright. All rights reserved.

13.
ACS Omega ; 6(44): 29940-29954, 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34778666

RESUMO

Natural small-molecule phenols (NSMPs) possess certain ubiquitous bioactivities including the anxiolytic effect. Ryanodine receptor 1 (RyR1) may be one of the potentially critical pharmacological targets for studying the anxiolytic activity of NSMPs. However, detailed molecular mechanisms of NSMPs have not been fully clarified. This research was intended to identify potent hRyR1 agonists from NSMPs and investigate whether RyR1 plays a role in their anxiolytic effect. Homology modeling and molecular docking analysis were performed using Accelrys Discovery Studio 2.5. The most appropriate concentrations of NSMPs to activate RyR1 were measured using the MTT assay. Fluorescence analyses of the intracellular calcium levels and western blotting analysis were carried out to validate whether NSMPs could regulate the calcium flux to some extent by activating RyR1. The results demonstrated that xanthotoxol and 5-hydroxy-1,4-naphthalenedione can be screened as hit compounds for potential agonists of hRyR1 to exert the anxiolytic effect. In conclusion, NSMPs might be a kind of pharmacological signal carrier, acting on RyR1 as an agonist and resulting in calcium ion mobilization from intracellular calcium ion store.

14.
Nanotechnology ; 33(9)2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34794130

RESUMO

A magnetically induced self-assembly DNAzyme electrochemical biosensor based on gold-modifiedα-Fe2O3/Fe3O4heterogeneous nanoparticles was successfully fabricated to detect Nickel(II) (Ni2+). The phase composition and magnetic properties ofα-Fe2O3/Fe3O4heterogeneous nanoparticles controllably prepared by the citric acid (CA) sol-gel method were investigated in detail. Theα-Fe2O3/Fe3O4heterogeneous nanoparticles were modified by using trisodium citrate as reducing agent, and the magnetically induced self-assemblyα-Fe2O3/Fe3O4-Au nanocomposites were obtained. The designed Ni2+-dependent DNAzyme consisted of the catalytic chain modified with the thiol group (S1-SH) and the substrate chain modified with methylene blue (S2-MB). The MGCE/α-Fe2O3/Fe3O4-Au/S1/BSA/S2 electrochemical sensing platform was constructed and differential pulse voltammetry was applied for electrochemical detection. Under the optimum experimental parameters, the detection range of the biosensor was 100 pM-10µM (R2 = 0.9978) with the limit of detection of 55 pM. The biosensor had high selectivity, acceptable stability, and reproducibility (RSD = 4.03%).

15.
Mikrochim Acta ; 188(12): 438, 2021 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-34839414

RESUMO

The rapid detection of insecticides such as parathion-methyl (PM) requires methods with high sensitivities and selectivities. Herein, a dual catalytic amplification strategy was developed using Fe3O4 nanozyme-supported carbon quantum dots and silver terephthalate metal-organic frameworks (Fe3O4/C-dots@Ag-MOFs) as current amplification elements. Based on this strategy, a novel electrochemical microfluidic paper-based chip was designed to detect PM. Fe3O4/C-dots@Ag-MOFs were synthesised by a hydrothermal method, and a molecularly imprinted polymer (MIP) was then synthesised on the surface of Fe3O4/C-dots@Ag-MOFs using PM as a template molecule. Finally, the reaction zone of a chip was modified with MIP/Fe3O4/C-dots@Ag-MOFs. PM from a sample introduced into the reaction zone was captured by the MIP, which generated a reduction current response at - 0.53 V in a three-electrode system embedded in the chip. Simultaneous catalysis by Fe3O4/C-dots and Ag-MOFs significantly enhanced the signal. The chip had a detection limit of 1.16 × 10-11 mol L-1 and was successfully applied to the determination of PM in agricultural products and environmental samples with recovery rates ranging from 82.7 to 109%, with a relative standard deviation (RSD) of less than 5.0%. This approach of combining a dual catalytic amplification strategy with an MIP significantly increased the sensitivity as well as selectivity of chips and can potentially be used to detect a wide variety of target analytes using microfluidic paper-based chips.

16.
J Inflamm Res ; 14: 5227-5239, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34675600

RESUMO

Purpose: Recent studies indicate that microglia and monocyte-derived macrophages (MDMs) have different roles in diseases such as stroke and spinal cord injury, yet their respective polarized phenotypes and roles remain unclear in spinal cord ischemia/reperfusion injury (SCIRI). Methods: We established a mouse model of SCIRI by transient aortic occlusion followed by reperfusion. Basso mouse scale (BMS) scores were used to test the locomotor functions. The histopathological changes in spinal cord were assessed by hematoxylin-eosin staining and NF-200 immunohistochemistry. Real-time PCR, immunofluorescence and flow cytometry were employed to analyze the polarized phenotypes of the microglia and infiltrating MDMs, and the resulting inflammatory responses. Furthermore, the role of infiltrating MDMs were investigated by MDMs depletion using systemic administration of clodronate-liposomes. Results: SCIRI significantly impaired locomotor function of mice, accompanied with progressed necrosis, infiltration of inflammatory cells and neuron loss in the spinal cord. M1-related pro-inflammatory markers (iNOS, CD16, CD86 and TNF-α) increased dramatically in the early phase following SCIRI. In contrast, M2-related anti-inflammatory markers (CD204 and CD206) elevated at later stage. Besides, the invading MDMs were principally pro-inflammatory M1 type, transiently restricted to the first week after SCIRI. In contrast, microglia were the main source of anti-inflammatory M2 type. Furthermore, depletion of MDMs by clodronate-liposomes significantly preserved neurological functions and relieved neuronal damage caused by SCIRI. Conclusion: These findings suggested distinct polarized status of resident microglia and MDMs following SCIRI. Inhibition of the invading MDMs may represent a novel approach for SCIRI treatment.

18.
Int Ophthalmol ; 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34633608

RESUMO

BACKGROUND: It has been gradually recognized that circular RNAs (circRNAs) are important modulators in multiple malignancies. Here, we analyzed the function of circ_0075804 and explored its associated mechanism in regulating retinoblastoma (RB) progression. METHODS: Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot assay were utilized to measure RNA and protein expression, respectively. Cell proliferation was analyzed by Cell counting kit-8 (CCK8) assay and 5-Ethynyl-2'-deoxyuridine (EdU) assay. Cell apoptosis was assessed by flow cytometry. Cell migration and invasion abilities were analyzed by wound healing assay and transwell invasion assay. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were applied to verify intermolecular target relations. Xenograft tumor model was used to analyze the role of circ_0075804 in tumor growth in vivo. RESULTS: Circ_0075804 expression was markedly up-regulated in RB tissues and cell lines. Circ_0075804 knockdown restrained the proliferation, migration and invasion whereas promoted the apoptosis of RB cells. Circ_0075804 acted as a molecular sponge for microRNA-138-5p (miR-138-5p), and circ_0075804 silencing-induced effects were partly reversed by miR-138-5p knockdown in RB cells. MiR-138-5p interacted with the 3' untranslated region (3'UTR) of paternally expressed 10 (PEG10). Circ_0075804 positively regulated PEG10 level by sponging miR-138-5p in RB cells. PEG10 overexpression largely overturned miR-138-5p overexpression-mediated effects in RB cells. Circ_0075804 knockdown blocked xenograft tumor growth in vivo. CONCLUSION: Circ_0075804 promoted RB progression via miR-138-5p-dependent regulation of PEG10, which provided new insight in RB therapy.

19.
Placenta ; 115: 97-105, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34598084

RESUMO

INTRODUCTION: Excessive activation of maternal systemic inflammation is one of the underlying causes of pathology during the disease course of preeclampsia (PE). The triggering receptor expressed on myeloid cells-1 (TREM-1) participates in the development and persistence of inflammation. We hypothesized that dysregulated TREM-1 may be involved in the pathogenesis of PE by promoting the secretion of trophoblastic pro-inflammatory cytokines that augment inflammation. METHODS: The localization of TREM-1 in placenta and the extravillous trophoblast cell line (TEV-1) was determined by immunohistochemical staining. The expression level of TREM-1 and pro-inflammatory cytokines in placentas were compared between normal pregnancies and PE. We used lipopolysaccharide (LPS) to simulate trophoblastic inflammation. TEV-1 cells were transfected with TREM-1 plasmid and si-TREM-1 respectively, and then were incubated with LPS. The expression levels of pro-inflammatory cytokines and key molecules featured in nuclear transcription factor-kappaB (NF-κB) pathway were detected. Transwell assays were used to detect the effects of TREM-1 on cell migration and invasion. RESULTS: TREM-1 was localized on both villous trophoblasts (VTs) and extravillous trophoblasts (EVTs). TREM-1 and pro-inflammatory cytokines were up-regulated in preeclamptic placenta. Overexpression of TREM-1 promoted the activation of NF-κB pathway and the release of pro-inflammatory factors induced by LPS, and enhanced migration and invasion of TEV-1 cells. Inhibition of TREM-1 significantly attenuated LPS-induced effects and suppressed migration and invasion. DISCUSSION: This study suggested that TREM-1 was up-regulated in PE, and may promote the production of downstream inflammatory factors by activating NF-κB pathway in trophoblastic cells, thus exerting pro-inflammatory effects in the pathogenesis of PE.

20.
BMC Cardiovasc Disord ; 21(1): 516, 2021 10 24.
Artigo em Inglês | MEDLINE | ID: mdl-34689730

RESUMO

BACKGROUND: The non-invasive quantitative evaluation of left ventricle (LV) function plays a critical role in clinical cardiology. This study proposes a novel ultrasonic biomechanics method by integrating both LV vortex and wall motion to fully assess and understand the LV structure and function. The purpose of this study was to validate the ultrasonic biomechanics method as a quantifiable approach to evaluate LV function. METHODS: Firstly, B-mode ultrasound images were acquired and processed, which were utilized to implement parameters for quantifying the LV vortex and wall motion respectively. Next, the parameters were compared in polyvinyl alcohol cryogen (PVA) phantoms with different degree of stiffness corresponding to different freezing and thawing cycles in vitro. Finally, the parameters were computed in vivo during one cardiac cycle to assess the LV function in normal and abnormal subjects in vivo. RESULTS: In vitro study, the velocity field of PVA phantom differed with stiffness (varied elasticity modulus). The peak of strain for wall motion decreases with the increase of elasticity modulus, and periodically changed values. Statistical analysis for parameters of vortex dynamics (energy dissipation index, DI; kinetic energy fluctuations, KEF; relative strength, RS; and vorticity, W) based on different elasticity (E) of phantom depicted the good viability of this algorithm. In vivo study, the results confirmed that subjects with LV dysfunction had lower vorticity and strain (S) compared to the normal group. CONCLUSION: Ultrasonic biomechanics method can obtain the vortex and wall motion of left ventricle. The method may have potential clinical value in evaluation of LV dysfunction.

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