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1.
Artigo em Inglês | MEDLINE | ID: mdl-34637922

RESUMO

Toll like receptor 5 (TLR5) plays a crucial role in the innate immune response by recognizing bacterial flagellin proteins. In the present study, the genomic and 5'-flanking sequences of LcTLR5M (membrane) and LcTLR5S (soluble) were cloned from the large yellow croaker, Larimichthys crocea. Then, their promoter activities were determined in human embryonic kidney (HEK293T) cells. LcTLR5M contained 4 exons and 3 introns, and LcTLR5S contained 2 exons and 1 intron. Bioinformatic prediction of transcription factor binding sites (TFBSs) indicated that the promoter structures were different between LcTLR5M and LcTLR5S. A dual luciferase assay showed that the deletion mutant -471 to +189 of LcTLR5M promoter possessed the greatest activity with 36 times activity of the control (P < 0.05). For LcTLR5S, two deletion mutants, -1687 to +106 and - 720 to +106, showed high promoter activity. Furthermore, site-directed mutation demonstrated that a -392 to -391 AT/GG substitution in Oct-1 binding site, and a -104 to -103 GG/TT and a -98 to -97 CC/AA substitution in the NF-κB binding site of TLR5S caused a significant decline of luciferase activity (P < 0.05). Moreover, the co-transfection of an NF-κB/p65 over-expression plasmid with wild type TLR5S (-720 to +106) resulted in an extremely significant increase of promoter activity by more than 9 times compared with the NF-kB mutant (P < 0.01). Our findings suggest that the genomic organization and promoter structure may differ between LcTLR5M and LcTLR5S. Oct1 and NF-κB binding sites might be cis-regulatory elements in the LcTLR5S promoter. NF-κB/p65 plays an important role in LcTLR5S promoter activation through binding with the NF-κB binding site.

2.
Chemosphere ; 286(Pt 1): 131541, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34293565

RESUMO

To effectively degrade organic pollutants in wastewater, visible-light-driven Bi2MoO6/PPy hierarchical heterogeneous photocatalysts were prepared through a solvothermal method and the following in-situ chemical oxidation polymerization. Compared with pristine Bi2MoO6 photocatalyst, the composite photocatalysts exhibited dramatically improved photocatalytic activity and photostability towards the degradation of methylene blue dye and tetracycline antibiotic. Bi2MoO6/PPy-80 sample achieved the highest photocatalytic degradation rates for methylene blue dye (93.6%) and tetracycline antibiotic (88.3%) under visible light irradiation. These two organic pollutants could be completely degraded into nontoxic small molecules according to in-depth HPLC-MS analysis of degradation products. The transient photocurrent responses, electrochemical impedance spectra, and photoluminescence spectra demonstrated that the introduction of PPy nanoparticles on the surface of Bi2MoO6 nanosheets could effectively accelerate the separation of photo-generated electron-hole pairs. Furthermore, a possible synergetic photocatalytic mechanism was put forward based on the electron spin resonance and XPS valence-band spectra. This work indicated that construction of hierarchical composite photocatalysts combining polypyrrole conductive polymer and Bi2MoO6 semiconductor in nanoscale is an efficient approach to improve photocatalytic activity for environmental remediation.


Assuntos
Poluentes Ambientais , Polímeros , Bismuto , Catálise , Descontaminação , Microesferas , Molibdênio , Pirróis
3.
Dalton Trans ; 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34825686

RESUMO

Many effluents contain various antibiotics commonly, where the simultaneous removal of them is a big challenge. In this study, the magnetic biocomposite (eggshell-zeolitic imidazolate framework) was designed and synthesized by green and facile method. Zeolitic imidazolate framework-8 (ZIF-8) particles were stabilized on the surface of magnetic eggshell (Fe3O4-ES), generating a new Fe3O4-ES/ZIF-8 adsorbent, which was also fully characterized using FTIR, XRD, SEM and BET techniques. Thereafter, norfloxacin (NOR) adsorption processes were investigated through different influencing factors (dosage, concentration, pH and temperature). The Langmuir adsorption isotherm could confirm a maximum removal efficiency of 80.13% for NOR. Kinetic studies illustrated that the pseudo-first-order model was in line with the experimental data of the simultaneous removal of NOR. Moreover, the magnetic nature of the adsorbent caused an easy separation from the aqueous solution.

4.
Eur J Pharmacol ; : 174616, 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34780752

RESUMO

High fructose has been reported to drive glomerular podocyte oxidative stress and then induce podocyte foot process effacement in vivo, which could be partly regarded as podocyte hypermotility in vitro. Atractylodin possesses anti-oxidative effect. The aim of this study was to explore whether atractylodin prevented against fructose-induced podocyte hypermotility via anti-oxidative property. In fructose-exposed conditionally immortalized human podocytes, we found that atractylodin inhibited podocyte hypermotility, and up-regulated slit diaphragm proteins podocin and nephrin, and cytoskeleton protein CD2-associated protein (CD2AP), α-Actinin-4 and synaptopodin expression, which were consistent with its anti-oxidative activity evidenced by up-regulation of catalase (CAT) and superoxide dismutase (SOD) 1 expression, and reduction of reactive oxygen species (ROS) production. Atractylodin also significantly suppressed expression of transient receptor potential channels 6 (TRPC6) and phosphorylated Ca2+/calmodulin-dependent protein kinase IV (CaMK4) in cultured podocytes with fructose exposure. Additionally, in fructose-exposed podocytes, CaMK4 siRNA up-regulated synaptopodin and reduced podocyte hypermotility, whereas, silencing of TRPC6 by siRNA decreased p-CaMK4 expression, inhibited podocyte hypermotility, showing TRPC6/p-CaMK4 signaling activation in podocyte hypermotility under fructose condition. Just like atractylodin, antioxidant N-acetyl-L-cysteine (NAC) could inhibit TRPC6/p-CaMK4 signaling activation to reduce fructose-induced podocytes hypermotility. These results first demonstrated that the anti-oxidative property of atractylodin may contribute to the suppression of podocyte hypermotility via inhibiting TRPC6/p-CaMK4 signaling and restoring synaptopodin expression abnormality.

5.
Mol Immunol ; 141: 1-12, 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34781186

RESUMO

Cryptocaryon irritans, a holotrichous ciliate parasitic protozoan, can trigger marine white spot disease and cause substantial economic losses in mariculture. However, methods of preventing and curing the disease have negatively affect fish, human, other organisms, and the natural environment. The antiparasitic activity of some antimicrobial peptides (AMPs) has garnered extensive attention of scholars. In this study, we identified and characterised a novel antiparasitic peptide, named So-pis, from Sciaenops ocellatus. The sequence analysis, structural features, and tissue distribution suggested that So-pis is genetically related to the piscidins family. However, So-pis showed a relatively low overall conservation compared with other known piscidins. So-pis is abound in glycine residues (22.7 %) and it has a neutral isoelectric point, weak amphipathicity, relatively long α-helix, and high hydrophobicity. These key elements are responsible for its biological activity. Quantitative real-time polymerase chain reaction (qRT-PCR) data indicated that So-pis is a typically gill-expressed peptide. The expression of So-pis in the gill, skin, spleen, and head kidney could be regulated during C. irritans infection, thereby implicating a role of So-pis in immune defence against C. irritans. The synthetic So-pis had limited or no antimicrobial activity against bacterial and yeasts but exhibited potent antiparasitic activity against C. irritans in vitro. The activity of synthetic So-pis against erythrocytes was less potent than its antiparasitic activity against C. irritans. These results indicated that So-pis might be one of the crucial defence cytokines against C. irritans in the red drum. Cumulatively, our data suggested that So-pis might be a potential candidate for developing a novel, effective, and safe therapeutic agent against marine white spot disease.

7.
Dentomaxillofac Radiol ; : 20210363, 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34762512

RESUMO

OBJECTIVES: Ultrasound emerges as a complement to cone-beam computed tomography in dentistry, but struggles with artifacts like reverberation and shadowing. This study seeks to help novice users recognize soft tissue, bone, and crown of a dental sonogram, and automate soft tissue height (STH) measurement using deep learning. METHODS: In this retrospective study, 627 frames from 111 independent cine loops of mandibular and maxillary premolar and incisors collected from our porcine model (N = 8) were labeled by a reader. 274 premolar sonograms, including data augmentation, were used to train a multi class segmentation model. The model was evaluated against several test sets, including premolar of the same breed (n = 74, Yucatan) and premolar of a different breed (n = 120, Sinclair). We further proposed a rule-based algorithm to automate STH measurements using predicted segmentation masks. RESULTS: The model reached a Dice similarity coefficient of 90.7±4.39%, 89.4±4.63%, and 83.7±10.5% for soft tissue, bone, and crown segmentation, respectively on the first test set (n = 74), and 90.0±7.16%, 78.6±13.2%, and 62.6±17.7% on the second test set (n = 120). The automated STH measurements have a mean difference (95% confidence interval) of -0.22 mm (-1.4, 0.95), a limit of agreement of 1.2 mm, and a minimum ICC of 0.915 (0.857, 0.948) when compared to expert annotation. CONCLUSION: This work demonstrates the potential use of deep learning in identifying periodontal structures on sonograms and obtaining diagnostic periodontal dimensions.

8.
J Med Chem ; 64(22): 16553-16572, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34783240

RESUMO

The leaves of Mitragyna speciosa (kratom), a plant native to Southeast Asia, are increasingly used as a pain reliever and for attenuation of opioid withdrawal symptoms. Using the tools of natural products chemistry, chemical synthesis, and pharmacology, we provide a detailed in vitro and in vivo pharmacological characterization of the alkaloids in kratom. We report that metabolism of kratom's major alkaloid, mitragynine, in mice leads to formation of (a) a potent mu opioid receptor agonist antinociceptive agent, 7-hydroxymitragynine, through a CYP3A-mediated pathway, which exhibits reinforcing properties, inhibition of gastrointestinal (GI) transit and reduced hyperlocomotion, (b) a multifunctional mu agonist/delta-kappa antagonist, mitragynine pseudoindoxyl, through a CYP3A-mediated skeletal rearrangement, displaying reduced hyperlocomotion, inhibition of GI transit and reinforcing properties, and (c) a potentially toxic metabolite, 3-dehydromitragynine, through a non-CYP oxidation pathway. Our results indicate that the oxidative metabolism of the mitragynine template beyond 7-hydroxymitragynine may have implications in its overall pharmacology in vivo.

9.
Int J Rheum Dis ; 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34796660

RESUMO

AIM: To investigate the predictive factors of pulmonary arterial hypertension (PAH) in systemic lupus erythematosus (SLE) patients. METHOD: This chart review study included 408 SLE patients. We defined PAH as 2 consecutive systolic pulmonary arterial pressure (PAP) values ≥40 mm Hg by echocardiography. Demographic characteristics, clinical symptoms, autoantibodies, and laboratory tests were studied. RESULTS: Thirty-four patients in the SLE/PAH+ group and 374 patients in the SLE/PAH- group were analyzed. The prevalence of PAH in SLE is 8.3% in this study. The occurrences of interstitial pneumonitis, polyserositis and myocardial damage were higher in the SLE/PAH+ group (P = .001, P = .033 and P < .001, respectively). The occurrence of anti-double-stranded DNA and anti-ribosomal RNA protein (anti-rRNP) antibodies were lower in the SLE/PAH+ group (P = .003, .010). Positive rates of anti-Sjögren's syndrome antigen A (anti-SSA)/Ro52 antibodies and anti-SSB antibodies were higher in the SLE/PAH+ group (P = .046, .021). C-reactive protein and immunoglobin G (IgG) were higher in the SLE/PAH+ group (P = .009, .005). Ejection fraction and SLE disease activity index between the 2 groups had no differences. Multivariable logistic regression indicated that interstitial pneumonitis, myocardial damage and high IgG are predictive factors for SLE-associated PAH patients. CONCLUSION: From this study, we found that interstitial pneumonitis, myocardial damage, and high IgG were predictive factors of PAH in SLE patients.

10.
Zhongguo Zhong Yao Za Zhi ; 46(19): 5052-5063, 2021 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-34738401

RESUMO

Compound Renshen Buqi Granules have been widely used to treat chronic heart failure(CHF) due to Qi deficiency and blood stasis, but the mechanism of action remains unclear. This paper explored the pathogenesis of CHF due to Qi deficiency and blood stasis and the intervention mechanism of Compound Renshen Buqi Granules based on quantitative proteomics for uncovering the biological basis. SD rats were divided into the normal control(N) group, normal+Compound Renshen Buqi Granules(ND) group, model(M) group, model+Compound Renshen Buqi Granules(D) group, and positive control(Y) group. The rat model of CHF due to Qi deficiency and blood stasis was established by ligation of the left anterior descending(LAD) coronary artery and chronic sleep deprivation. The rats in the ND group and D group were provided with Compound Renshen Buqi Granules, while those in the Y group received valsartan. Six weeks later, the serum was sampled and the data-dependent acquisition(DDA) was employed for the non-targeted quantitative proteomics analysis of the differences in protein expression among groups, followed by the targeted analysis of differentially expressed proteins(DEPs) generated by data-independent acquisition(DIA). Compared with the N group, the rats in the M group pre-sented with decreased body weight, grip strength, and pulse amplitude and increased RGB value on the tongue surface. The pathomorphological examination revealed inflammatory cell infiltration, cell degeneration and necrosis, tissue fibrosis, etc. After the intervention with Compound Renshen Buqi Granules, multiple indicators were reversed. As demonstrated by proteomics results, there were 144 and 111 DEPs found in the M group and ND group in comparison with the N group. Compared with the M group, 107 and 194 DEPs were found in the D group and the Y group, respectively. Compared with the ND group, 119 DEPs were detected in the D group. As illustrated by DIA-based verification, the quantitative results of six proteins in each group were consistent with those by DDA. The syndrome indicators and pathomorphological examination results demonstrated that the protein expression profile of rats with CHF due to Qi deficiency and blood stasis changed obviously. However, Compound Renshen Buqi Granules were able to reverse the differential expression of immune proteins to regulate CHF of Qi deficiency and blood stasis syndrome, which has provided clues for figuring out the pathogenesis of CHF due to Qi deficiency and blood stasis and the intervention mechanism of Compound Renshen Buqi Granules.


Assuntos
Insuficiência Cardíaca , Panax , Animais , Insuficiência Cardíaca/tratamento farmacológico , Medicina Tradicional Chinesa , Proteômica , Qi , Ratos , Ratos Sprague-Dawley
11.
J Diabetes Res ; 2021: 8757996, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34671683

RESUMO

Background: Triglyceride-glucose (TyG) index is a convenient indicator of insulin resistance. It has been shown to be associated with macrovascular and microvascular complications in nonhospitalized diabetic patients. However, whether TyG index is a risk factor of diabetes vascular complications in hospitalized type 2 diabetic patients is unclear. We sought to explore the association between TyG index and the risk of macrovascular and microvascular complications in a large Chinese cohort of hospitalized patients. Method: A total of 4,721 patients with type 2 diabetes (T2D) who were hospitalized in the Department of Endocrinology, Kunshan Hospital Affiliated to Jiangsu University were enrolled between January 2015 and November 2020. TyG index was calculated as ln[fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. Measures of macrovascular complications included brachial-ankle pulse wave velocity (ba-PWV) and ankle-brachial index (ABI), whilst urine microalbumin (MAU), chronic kidney disease (CKD), and diabetic retinopathy (DR) were evaluated for microvascular complications. Logistic regressions were used to examine the association between TyG index and diabetes complications. Results: In univariate logistic regressions, higher TyG index was significantly (p < 0.002) associated with increased odds of MAU (OR = 1.39, 95% CI: [1.22~1.59]) and ABI (OR = 1.31, 95% CI: [1.10-1.57]) but not CKD, DR, or ba-PWV. After controlling for confounders such as age, sex, and body mass index (BMI), TyG index remained strongly (p < 0.002) associated with MAU and ABI. These associations were more pronounced (p < 0.001) in patients with poor glycemic control or in the elderly. Conclusion: Hospitalized patients with an elevated TyG index were at a higher risk of lower limb vascular stenosis and nephric microvascular damage. Close monitoring of TyG index in patients with younger age or poor glycemic control could potentially reduce the burden of diabetes complications and prevent readmission.

12.
ACS Appl Mater Interfaces ; 13(41): 48881-48888, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34609130

RESUMO

In this work, we propose that 1,1,3,3-tetramethyldisiloxane (TMDS) is beneficial for electrochemical property enhancement of LiNi0.5Mn1.5O4/Li cells at high temperatures. The LiNi0.5Mn1.5O4/Li cells with 1 vol % TMDS revealed capacity retention of 81.2% after a cycling test at 55 °C, while the cells without additive showed capacity retention of only 32.3%. The cells with 1 vol % TMDS also presented a better rate performance, reaching 100 mAh g-1 under 3C. Physical characterization and theoretical calculations revealed that TMDS formed a thinner and better conductive layer on the LiNi0.5Mn1.5O4 surface and effectively scavenged HF/F- from the electrolyte, contributing to high stabilization of LiNi0.5Mn1.5O4.

14.
Clin Lab ; 67(10)2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34655210

RESUMO

BACKGROUND: CD14 is a pattern recognition receptor constitutively expressed in different types of immune cells, either in a membrane-anchored (mCD14) or in a soluble (sCD14) form. This study investigated whether hepatic CD14 expression levels were correlated with the grades of liver inflammation as well as the potential usefulness of serum sCD14 as a biomarker for predicting liver inflammation in chronic hepatitis B (CHB) patients with normal or mildly elevated ALT. METHODS: A total of 216 treatment-naive CHB patients with normal or mildly elevated ALT who underwent liver biopsy were recruited. Hepatic expression level of CD14 was measured using immunohistochemistry and real-time PCR. Serum sCD14 concentrations were determined with an enzyme-linked immunosorbent assay. Correlations between hepatic CD14, serum sCD14, and liver inflammation grade were analyzed. Univariate and multivariate analysis were performed to identify significant liver inflammation-associated factors. The receiver operating characteristic curve was used to assess the discriminating power of serum sCD14 to significant liver inflammation in CHB patients with normal or mildly elevated ALT. RESULTS: Both hepatic expression levels of CD14 and serum sCD14 concentrations significantly increased with the aggravation of liver inflammation. Moreover, hepatic expression levels of CD14, serum sCD14 concentrations, and liver inflammation grades were positively correlated with each other. Three parameters including alkaline phosphatase (ALP), neutrophil, and sCD14 were identified as independent predictors of significant liver inflammation. Subsequently, a diagnostic equation named model-sCD14 was developed incorporating sCD14 and other variables (ALP and neutrophils) with p < 0.05 in multivariate logistic analysis. The area under receiver operating characteristic curve (AUC) of sCD14 for predicting significant liver inflammation was 0.788 and the optimal cutoff was 27.14 ng/mL, with a sensitivity of 66.67%, a specificity of 81.70%, positive predictive value of 60.01%, and negative predictive value of 85.62%. When sCD14 was replaced by model-sCD14, the AUC value increased from 0.788 to 0.843 (z = 2.311, p = 0.021), with sensitivity of 77.78%, specificity of 77.12%, positive predictive value of 58.33%, and negative predictive value of 89.39%. CONCLUSIONS: Serum sCD4 has the potential to discriminate significant liver inflammation from CHB patients with normal or mildly increased ALT levels.


Assuntos
Hepatite B Crônica , Receptores de Lipopolissacarídeos , Alanina Transaminase , Biomarcadores , Hepatite B Crônica/diagnóstico , Humanos , Inflamação/diagnóstico , Fígado
15.
Org Biomol Chem ; 19(41): 8934-8939, 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34636833

RESUMO

A series of half-sandwich Ir(III) complexes 1-6 bearing an amidato bidentate ligand were conveniently synthesized and applied to the catalytic Leuckart-Wallach reaction to produce racemic α-chiral primary amines. With 0.1 mol% of complex 1, a broad range of ketones, including aryl ketones, dialkyl ketones, cyclic ketones, α-keto acids, α-keto esters and diketones, could be transformed to their corresponding primary amines with moderate to excellent yields (40%-95%). Asymmetric transformation was also attempted with chiral Ir complexes 3-6, and 16% ee of the desired primary amine was obtained. Despite the unsatisfactory enantio-control achieved so far, the current exploration might stimulate more efforts towards the discovery of better chiral catalysts for this challenging but important transformation.

16.
Peptides ; 146: 170668, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34624430
17.
Biomolecules ; 11(10)2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34680158

RESUMO

Most opioid analgesics used clinically, including morphine and fentanyl, as well as the recreational drug heroin, act primarily through the mu opioid receptor, a class A Rhodopsin-like G protein-coupled receptor (GPCR). The single-copy mu opioid receptor gene, OPRM1, undergoes extensive alternative splicing, creating multiple splice variants or isoforms via a variety of alternative splicing events. These OPRM1 splice variants can be categorized into three major types based on the receptor structure: (1) full-length 7 transmembrane (TM) C-terminal variants; (2) truncated 6TM variants; and (3) single TM variants. Increasing evidence suggests that these OPRM1 splice variants are pharmacologically important in mediating the distinct actions of various mu opioids. More importantly, the OPRM1 variants can be targeted for development of novel opioid analgesics that are potent against multiple types of pain, but devoid of many side-effects associated with traditional opiates. In this review, we provide an overview of OPRM1 alternative splicing and its functional relevance in opioid pharmacology.

18.
J Ethnopharmacol ; 284: 114783, 2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34715300

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Capsella bursa-pastoris (L.) Medic. (CBP) is a cruciferous plant valuable in reducing fever, improving eyesight and calming the liver. This herb was recorded in the Compendium of Materia Medica for cataract treatment. AIM OF THE STUDY: To determine the effects and mechanism of CBP on cataract prevention and treatment using a selenite cataract model. MATERIALS AND METHODS: The main compounds in CBP extract were analyzed by UPLC, 1H-NMR and 13C-NMR spectroscopic techniques. Flavonoids formed a significant proportion of its compounds, thus necessitating an evaluation of their inhibitory effects on the development of cataract using a selenite cataract model. The protective effects of CBP flavonoids (CBPF) against oxidative damage and the modulation of mitochondrial apoptotic pathway were subsequently verified on H2O2-treated SRA01/04 lens epithelial cells. RESULTS: CBPF significantly alleviated the development of cataract by decreasing the MDA level and increasing the GSH-Px and SOD levels in the lens. It also inhibited H2O2-induced apoptosis in SRA01/04 cells, increased the expression of Bcl-2 protein and decreased the expressions of Caspase-3 and Bax proteins. CONCLUSION: CBPF exerts a significant preventive effect on cataract development by regulating the mitochondrial apoptotic pathway of the lens epithelial cells. It is thus a potent traditional Chinese medicine (TCM) whose application should be further developed for the clinical treatment of cataract.

19.
Molecules ; 26(20)2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34684716

RESUMO

Lipid deposition in the kidney can cause serious damage to the kidney, and there is an obvious epithelial-mesenchymal transition (EMT) and fibrosis in the late stage. To investigate the interventional effects and mechanisms of phenolic compounds from Mori Cortex on the EMT and fibrosis induced by sodium oleate-induced lipid deposition in renal tubular epithelial cells (NRK-52e cells), and the role played by CD36 in the adjustment process, NRK-52e cells induced by 200 µmol/L sodium oleate were given 10 µmoL/L moracin-P-2″-O-ß-d-glucopyranoside (Y-1), moracin-P-3'-O-ß-d-glucopyranoside (Y-2), moracin-P-3'-O-α-l-arabinopyranoside (Y-3), and moracin-P-3'-O-[ß-glucopyranoside-(1→2)arabinopyranoside] (Y-4), and Oil Red O staining was used to detect lipid deposition. A Western blot was used to detect lipid deposition-related protein CD36, inflammation-related protein (p-NF-κB-P65, NF-κB-P65, IL-1ß), oxidative stress-related protein (NOX1, Nrf2, Keap1), EMT-related proteins (CD31, α-SMA), and fibrosis-related proteins (TGF-ß, ZEB1, Snail1). A qRT-PCR test detected inflammation, EMT, and fibrosis-related gene mRNA levels. The TNF-α levels were detected by ELISA, and the colorimetric method was used to detects SOD and MDA levels. The ROS was measured by flow cytometry. A high-content imaging analysis system was applied to observe EMT and fibrosis-related proteins. At the same time, the experiment silenced CD36 and compared the difference between before and after drug treatment, then used molecular docking technology to predict the potential binding site of the active compounds with CD36. The research results show that sodium oleate can induce lipid deposition, inflammation, oxidative stress, and fibrosis in NRK-52e cells. Y-1 and Y-2 could significantly ameliorate the damage caused by sodium oleate, and Y-2 had a better ameliorating effect, while there was no significant change in Y-3 or Y-4. The amelioration effect of Y-1 and Y-2 disappeared after silencing CD36. Molecular docking technology showed that the Y-1 and Y-2 had hydrogen bonds to CD36 and that, compared with Y-1, Y-2 requires less binding energy. In summary, moracin-P-2″-O-ß-d-glucopyranoside and moracin-P-3'-O-ß-d-glucopyranoside from Mori Cortex ameliorated lipid deposition, EMT, and fibrosis induced by sodium oleate in NRK-52e cells through CD36.


Assuntos
Transição Epitelial-Mesenquimal/efeitos dos fármacos , Morus/metabolismo , Extratos Vegetais/farmacologia , Animais , Linhagem Celular , China , Células Epiteliais/efeitos dos fármacos , Transição Epitelial-Mesenquimal/fisiologia , Fibrose , Inflamação/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Rim/efeitos dos fármacos , Medicina Tradicional Chinesa/métodos , Simulação de Acoplamento Molecular , Fator 2 Relacionado a NF-E2/metabolismo , Ratos , Transdução de Sinais/efeitos dos fármacos , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
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