RESUMEN
Lung injury has been a serious medical problem that requires new therapeutic approaches and biomarkers. Circular RNAs (circRNAs) are non-coding RNAs (ncRNAs) that exist widely in eukaryotes. CircRNAs are single-stranded RNAs that form covalently closed loops. CircRNAs are significant gene regulators that have a role in the development, progression, and therapy of lung injury by controlling transcription, translating into protein, and sponging microRNAs (miRNAs) and proteins. Although the study of circRNAs in lung injury caused by pulmonary toxicants is just beginning, several studies have revealed their expression patterns. The function that circRNAs perform in relation to pulmonary toxicants (severe acute respiratory distress syndrome coronavirus-2 (SARS-CoV-2), drug abuse, PM2.5, and cigarette smoke) is the main topic of this review. A variety of circRNAs can serve as potential biomarkers of lung injury. In this review, the biogenesis, properties, and biological functions of circRNAs were concluded, and the relationship between circRNAs and pulmonary toxicants was discussed. It is expected that the new ideas and potential treatment targets that circRNAs provide would be beneficial to research into the molecular mechanisms behind lung injury.
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Lesión Pulmonar , MicroARNs , Humanos , ARN Circular/genética , Lesión Pulmonar/inducido químicamente , Lesión Pulmonar/genética , Lesión Pulmonar/terapia , Pulmón/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Biomarcadores/metabolismoRESUMEN
Large yellow croaker (Larimichthys crocea) is a vital marine-cultured species in China. Large yellow croaker iridovirus (LYCIV) can cause a high mortality rate in L. crocea. Rapid and convenient detection of LYCIV is an urgent demand for diagnosis. In this study, rapid and simple recombinase polymerase amplification (RPA), real-time RPA and RPA combined with lateral flow dipstick (RPA-LFD) methods were developed for the detection of LYCIV based on the conserved sequence of the LYCIV major capsid protein (MCP) gene. With these optimized RPA analyses, LYCIV detection could be completed within 20 min at 40°C. Both RPA and real-time RPA could detect viral DNA as low as 102 copies/µL, while the detection limit of RPA-LFD was 101 copies/µL, and there was no cross-reaction with other aquatic pathogens (KHV, CyHV-2, GCRV-JX01, SVCV, LCDV and LMBV). In practical evaluation of RPA, real-time RPA and RPA-LFD methods, the results showed consistency with the general PCR detection. In short, the developed RPA, real-time RPA and RPA-LFD analyses could be simple, rapid, sensitive and reliable methods for field diagnosis of LYCIV infection and have significant potential in the protection of LYCIV infection.
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Infecciones por Virus ADN , Enfermedades de los Peces , Iridovirus , Técnicas de Amplificación de Ácido Nucleico , Perciformes , Sensibilidad y Especificidad , Animales , Perciformes/virología , Enfermedades de los Peces/virología , Enfermedades de los Peces/diagnóstico , Infecciones por Virus ADN/veterinaria , Infecciones por Virus ADN/diagnóstico , Infecciones por Virus ADN/virología , Iridovirus/aislamiento & purificación , Iridovirus/genética , Técnicas de Amplificación de Ácido Nucleico/veterinaria , Técnicas de Amplificación de Ácido Nucleico/métodos , ADN Viral/genética , Proteínas de la Cápside/genéticaRESUMEN
RATIONALE: Obesity leads to resistant hypertension and mechanisms are poorly understood, but high plasma levels of leptin have been implicated. Leptin increases blood pressure acting both centrally in the dorsomedial hypothalamus and peripherally. Sites of the peripheral hypertensive effect of leptin have not been identified. We previously reported that leptin enhanced activity of the carotid sinus nerve, which transmits chemosensory input from the carotid bodies (CBs) to the medullary centers, and this effect was abolished by nonselective blockers of Trp (transient receptor potential) channels. We searched our mouse CB transcriptome database and found that the Trpm7 (transient receptor potential melastatin 7) channel was the most abundant Trp channel. OBJECTIVE: To examine if leptin induces hypertension acting on the CB Trpm7. METHODS AND RESULTS: C57BL/6J (n=79), leptin receptor (LepRb) deficient db/db mice (n=22), and LepRb-EGFP (n=4) mice were used. CB Trpm7 and LepRb gene expression was determined and immunohistochemistry was performed; CB glomus cells were isolated and Trpm7-like current was recorded. Blood pressure was recorded continuously in (1) leptin-treated C57BL/6J mice with intact and denervated CB; (2) leptin-treated C57BL/6J mice, which also received a nonselective Trpm7 blocker FTY720 administered systemically or topically to the CB area; (3) leptin-treated C57BL/6J mice transfected with Trpm7 small hairpin RNA to the CB, and (4) Leprb deficient obese db/db mice before and after Leprb expression in CB. Leptin receptor and Trpm7 colocalized in the CB glomus cells. Leptin induced a nonselective cation current in these cells, which was inhibited by Trpm7 blockers. Leptin induced hypertension in C57BL/6J mice, which was abolished by CB denervation, Trpm 7 blockers, and Trpm7 small hairpin RNA applied to CBs. Leprb overexpression in CB of Leprb-deficient db/db mice demethylated the Trpm7 promoter, increased Trpm7 gene expression, and induced hypertension. CONCLUSIONS: We conclude that leptin induces hypertension acting on Trmp7 in CB, which opens horizons for new therapy.
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Presión Sanguínea , Cuerpo Carotídeo/metabolismo , Hipertensión/inducido químicamente , Leptina , Receptores de Leptina/metabolismo , Canales Catiónicos TRPM/metabolismo , Animales , Antihipertensivos/farmacología , Presión Sanguínea/efectos de los fármacos , Cuerpo Carotídeo/efectos de los fármacos , Cuerpo Carotídeo/fisiopatología , Desnervación , Modelos Animales de Enfermedad , Hipertensión/metabolismo , Hipertensión/fisiopatología , Hipertensión/prevención & control , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Obesidad/complicaciones , Receptores de Leptina/deficiencia , Receptores de Leptina/genética , Transducción de Señal , Canales Catiónicos TRPM/antagonistas & inhibidores , Canales Catiónicos TRPM/genéticaRESUMEN
CONTEXT: Ginsenoside Rb1, the main active ingredient of ginseng, exhibits ex vivo depression of store-operated calcium entry (SOCE) and related vasoconstriction in pulmonary arteries derived from pulmonary hypertension (PH) rats. However, the in vivo effects of ginsenoside Rb1 on PH remain unclear. OBJECTIVE: This study explored the possibility of using ginsenoside Rb1 as an in vivo preventive medication for type I PH, i.e., pulmonary arterial hypertension (PAH), and potential mechanisms involving SOCE. MATERIALS AND METHODS: Male Sprague-Dawley rats (170-180 g) were randomly divided into Control, MCT, and MCT + Rb1 groups (n = 20). Control rats received only saline injection. Rats in the MCT + Rb1 and MCT groups were intraperitoneally administered single doses of 50 mg/kg monocrotaline (MCT) combined with 30 mg/kg/day ginsenoside Rb1 or equivalent volumes of saline for 21 consecutive days. Subsequently, comprehensive parameters related to SOCE, vascular tone, histological changes and hemodynamics were measured. RESULTS: Ginsenoside Rb1 reduced MCT-induced STIM1, TRPC1, and TRPC4 expression by 35.00, 31.96, and 32.24%, respectively, at the protein level. SOCE-related calcium entry and pulmonary artery contraction decreased by 162.6 nM and 71.72%. The mean pulmonary artery pressure, right ventricle systolic pressure, and right ventricular mass index decreased by 19.5 mmHg, 21.6 mmHg, and 39.50%. The wall thickness/radius ratios decreased by 14.67 and 17.65%, and the lumen area/total area ratios increased by 18.55 and 15.60% in intrapulmonary vessels with 51-100 and 101-150 µm o.d. CONCLUSION: Ginsenoside Rb1, a promising candidate for PH prevention, inhibited SOCE and related pulmonary vasoconstriction, and relieved MCT-induced PAH in rats.
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Calcio/metabolismo , Ginsenósidos/farmacología , Hipertensión Arterial Pulmonar/prevención & control , Animales , Modelos Animales de Enfermedad , Masculino , Monocrotalina , Panax/química , Arteria Pulmonar/efectos de los fármacos , Arteria Pulmonar/metabolismo , Ratas , Ratas Sprague-Dawley , Vasoconstricción/efectos de los fármacosRESUMEN
During the pathogenetic process of varied kidney diseases, renal tubules are the major sites in response to detrimental insults, including pro-inflammatory stimuli. MicroRNA-204-5p (miR-204-5p) can be detected in the renal tubular epithelial cells in the normal kidney; its expression, however, is downregulated in the kidney with pathological changes. This study aimed to investigate the role of miR-204-5p in interleukin 6 (IL6) mediated inflammatory response and chemokine production in HK-2 renal tubular cells. In HK-2 cells, the expression of miR-204-5p was downregulated in response to exogenous pro-inflammatory stimulus, tumor necrosis factor α (TNFα), or IL1ß, while that of IL6 receptor α (IL6R) was upregulated. Dual-luciferase results confirmed that miRNA-204-5p directly targeted IL6R. In addition to suppressing IL6R expression, miRNA-204-5p agomir also inhibited the phosphorylation of signal transducer and activator of transcription 3 (STAT3) in HK-2 cells exposed to exogenous IL6. Further, miRNA-204-5p suppressed the overproduction of pro-inflammatory mediators (cyclooxygenase 2 and prostaglandin E2) and chemokines (C-C motif chemokine ligand 2 and C-X-C motif chemokine ligand 8). The anti-inflammatory effects of miRNA-204-5p were attenuated when IL6R was reexpressed in HK-2 cells. Collectively, our study reveals that miR-204-5p inhibits the inflammation and chemokine generation in renal tubular epithelial cells by modulating the IL6/IL6R axis.
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Quimiocina CCL2/biosíntesis , Células Epiteliales/metabolismo , Interleucina-6/metabolismo , Interleucina-8/biosíntesis , Túbulos Renales Proximales/metabolismo , MicroARNs/metabolismo , Receptores de Interleucina-6/metabolismo , Línea Celular , Quimiocina CCL2/genética , Células Epiteliales/patología , Humanos , Inflamación/genética , Inflamación/metabolismo , Inflamación/patología , Interleucina-6/genética , Interleucina-8/genética , Túbulos Renales Proximales/patología , MicroARNs/genética , Receptores de Interleucina-6/genéticaRESUMEN
BACKGROUND/AIMS: Pulmonary arterial hypertension (PAH) is a severe and debilitating disease characterized by remodeling of the pulmonary vessels, which is driven by excessive proliferation and migration and apoptosis resistance in pulmonary artery smooth muscle cells (PASMCs). The calcineurin (CaN)/nuclear factor of activated T-cells (NFAT) signaling pathway is the most important downstream signaling pathway of store-operated Ca2+ entry (SOCE), which is increased in PAH. CaN/NFAT has been reported to contribute to abnormal proliferation in chronic hypoxia (CH)-induced PAH. However, the effect of CaN/NFAT signaling on PASMC proliferation, migration and apoptosis in monocrotaline (MCT)-induced PAH remains unclear. METHODS: PAH rats were established by a single intraperitoneal injection of MCT for 21 days. PASMCs were isolated and cultured in normal and MCT-induced PAH Sprague-Dawley rat. PASMCs were treated with CsA targeting CaN and siRNA targeting NFATc2-4 gene respectively by liposome. We investigated the expression of calcineurin/NFAT signaling by immunofluorescence, qRT-PCR and Western blotting methods. Cell proliferation was monitored using MTS reagent or by assessing proliferating cell nuclear antigen (PCNA) expression. Cell apoptosis was evaluated with an Annexin V - FITC/propidium iodide (PI) apoptosis kit by flow cytometry. PASMC migration was assessed with a Transwell chamber. RESULTS: MCT successfully induced PAH and pulmonary vascular remodeling in rats. CaN phosphatase activity and nuclear translocation of NFATc2-4 were increased in PASMCs derived from MCT-treated rats. In addition, CaNBß/NFATc2-4 expression was amplified at the mRNA and protein levels. PASMC proliferation and migration were markedly inhibited in a dosedependent manner by cyclosporin A (CsA). Furthermore, siRNA targeting NFATc2 and NFATc4 attenuated the excessive proliferation and migration and apoptosis resistance in PASMCs derived from both CON and MCT-treated rats, while NFATc3 knockdown specifically affected MCT-PASMCs. CONCLUSION: Our results demonstrate that CaN/NFAT signaling is activated and involved in the modulation of PASMC proliferation, migration and apoptosis in MCT-induced PAH.
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Apoptosis , Calcineurina/metabolismo , Proliferación Celular , Hipertensión Pulmonar/patología , Factores de Transcripción NFATC/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Animales , Apoptosis/efectos de los fármacos , Calcineurina/química , Hipoxia de la Célula , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Ciclosporina/farmacología , Modelos Animales de Enfermedad , Hipertensión Pulmonar/inducido químicamente , Hipertensión Pulmonar/metabolismo , Masculino , Monocrotalina/toxicidad , Miocitos del Músculo Liso/citología , Miocitos del Músculo Liso/metabolismo , Factores de Transcripción NFATC/antagonistas & inhibidores , Factores de Transcripción NFATC/genética , Proteínas del Tejido Nervioso/antagonistas & inhibidores , Proteínas del Tejido Nervioso/genética , Antígeno Nuclear de Célula en Proliferación/metabolismo , Arteria Pulmonar/citología , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Ratas , Ratas Sprague-Dawley , Transducción de SeñalRESUMEN
A collection of 36 thiosemicarbazone analogues possessed a broad span of tyrosinase inhibitory activities was designed and obtained. Robust and reliable CoMFA and CoMSIA models were gained to predict the structure-activity relationship and the new modifier direction. Inhibitory activities of the compounds were found to greatly depend upon molecular shape, size, and charge. The sterically bulky group at the C-4 position of the thiophene ring contributed a high capacity for biological activity. Some bulky substituents at the C1-position and C12-position, and electron-negative groups at the C3-position, helped to improve the activity of these analogues. The molecular docking results provided visual evidence for QSAR analysis and detailed information about binding mode, affinity, and the principal mechanism between the ligands and tyrosinase. Based on these, a prospective structure modification and optimization of the most potent compound, T32, was suggested for further research.
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Inhibidores Enzimáticos/química , Monofenol Monooxigenasa/antagonistas & inhibidores , Relación Estructura-Actividad Cuantitativa , Tiosemicarbazonas/química , Sitios de Unión , Dominio Catalítico , Inhibidores Enzimáticos/metabolismo , Simulación del Acoplamiento Molecular , Monofenol Monooxigenasa/metabolismo , Tiosemicarbazonas/metabolismoRESUMEN
This study was designed to observe the differences between main pulmonary arteries and the third-order branches of pulmonary arteries in the contractile response to phenylephrine (Phen), endothelin-1 (ET-1) and potassium chloride (KCl). The vascular tension changes of main and the third-order branches of pulmonary arteries induced by KCl, ET-1 and Phen were recorded by traditional vascular tone detection methods and microvascular ring technique, respectively. The results showed that Phen could cause a significant contraction in main pulmonary arteries, but did not induce apparent contraction in the third-order branches of pulmonary arteries. Compared with main pulmonary arteries, ET-1 contracted the third-order branches of pulmonary arteries with reduced maximal response value and PD2 value. In comparison with the main pulmonary arteries, contraction caused by KCl was enhanced in the third-order branches of pulmonary arteries. The results suggest that the vascular reactivity of main and the third-order branches of pulmonary arteries is different and it is important to study the vascular function of small branches of pulmonary arteries. This study could provide an important experimental basis for the further study on vascular function of small branches of pulmonary arteries and the functional changes in pulmonary hypertension.
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Endotelina-1/farmacología , Fenilefrina/farmacología , Cloruro de Potasio/farmacología , Arteria Pulmonar/efectos de los fármacos , Vasoconstricción , Animales , Masculino , RatasRESUMEN
SCOPE: Vitexin, a C-glycosylated flavonoid, is abundant in food sources and has potential health-beneficial properties. However, the targets for its beneficial effects remain largely unknown. This study aims to establish an in vitro cell model of vascular low-grade inflammation and explore the antiinflammatory mechanism of vitexin. METHODS AND RESULTS: Low-dose TNFα and IL-17 are combined to establish a cell model of vascular low-grade inflammation. Cell-based studies show that low-dose TNFα (1 ng mL-1) alone has a slight effect, but its combination with IL-17 can potently induce protein expression of inflammatory cytokines, leading to an inflammatory state. However, the vascular inflammation caused by low-dose TNF plus IL-17 does not lead to oxidative stress, and reactive oxygen species (ROS) does not involved in developing this inflammation. Vitexin can be absorbed by human umbilical vein endothelial (HUVEC) cells to increase the Nrf2 protein level and attenuate inflammation. In addition, the antiinflammatory effect of vitexin is blocked by the knockdown of Nrf2. Further localized surface plasmon resonance, drug affinity responsive target stability, and molecular docking demonstrate that vitexin can directly interact with Keap1 to disrupt Keap1-Nrf2 interaction and thus activate Nrf2. Treatment of mice with a bolus oral gavage of vitexin (100 mg kg-1 body weight) or a high-fat diet supplemented with vitexin (5 mg kg-1 body weight per day) for 12 weeks confirms the rapid increase in blood vitexin levels and subsequent incorporation into blood vessels to activate Nrf2 and ameliorate inflammation in vivo. CONCLUSION: The findings provide a reliable cell model of vascular low-grade inflammation and indicate Nrf2 protein as the potential target of vitexin to inhibit vascular inflammation.
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Apigenina , Factor 2 Relacionado con NF-E2 , Factor de Necrosis Tumoral alfa , Humanos , Animales , Ratones , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Interleucina-17/metabolismo , Simulación del Acoplamiento Molecular , Estrés Oxidativo , Transducción de Señal , Inflamación/tratamiento farmacológico , Peso CorporalRESUMEN
BACKGROUND: Pulmonary hypertension (PH) is characterized by profound vascular remodeling and alterations in Ca(2+) homeostasis in pulmonary arterial smooth muscle cells (PASMCs). Multiple transient receptor potential melastatin-related (TRPM) subtypes have been identified in vascular tissue. However, the changes in the expression and function of TRPM channels in pulmonary hypertension have not been characterized in detail. METHODS: We examined the expression of TRPM channels and characterized the functions of the altered TRPM channels in two widely used rat models of chronic hypoxia (CH)- and monocrotaline (MCT)-induced PH. RESULTS: CH-exposed and MCT-treated rats developed severe PH and right ventricular hypertrophy, with a significant decrease in TRPM8 mRNA and protein expression in pulmonary arteries (PAs). The downregulation of TRPM8 was associated with significant reduction in menthol-induced cation-influx. Time-profiles showed that TRPM8 down-regulation occurred prior to the increase of right ventricular systolic pressure (RVSP) and right ventricular mass index (RVMI) in CH-exposed rats, but these changes were delayed in MCT-treated rats. The TRPM8 agonist menthol induced vasorelaxation in phenylephrine-precontracted PAs, and the vasorelaxing effects were significantly attenuated in PAs of both PH rat models, consistent with decreased TRPM8 expression. CONCLUSION: Downregulation of TRPM8 may contribute to the enhanced vasoreactivity in PH.
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Hipertensión Pulmonar/metabolismo , Arteria Pulmonar/metabolismo , Canales Catiónicos TRPM/metabolismo , Animales , Cationes/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Fura-2/química , Hipertensión Pulmonar/inducido químicamente , Hipertensión Pulmonar/etiología , Hipertrofia Ventricular Derecha/inducido químicamente , Hipertrofia Ventricular Derecha/metabolismo , Hipertrofia Ventricular Derecha/patología , Hipoxia , Pulmón/irrigación sanguínea , Masculino , Manganeso/metabolismo , Mentol/farmacología , Monocrotalina/toxicidad , Ratas , Ratas Sprague-Dawley , Canales Catiónicos TRPM/agonistas , Canales Catiónicos TRPM/genética , Vasodilatación/efectos de los fármacosRESUMEN
Industry-generated trans-fatty acids (TFA) are detrimental to risk of CHD, but ruminant-originated TFA have been reported as neutral or equivocal. Therefore, the total TFA amount should not be the only factor considered when measuring the effects of TFA. In the present study, we addressed whether a version of the TFA index that unifies the effects of different TFA isomers into one equation could be used to reflect CHD risk probability (RP). The present cross-sectional study involved 2713 individuals divided into four groups that represented different pathological severities and potential risks of CHD: acute coronary syndrome (ACS, n 581); chronic coronary artery disease (CCAD, n 631); high-risk population (HRP, n 659); healthy volunteers (HV, n 842). A 10-year CHD RP was calculated. Meanwhile, the equation of the TFA index was derived using five TFA isomers (trans-16 : 1n-7, trans-16 : 1n-9, trans-18 : 1n-7, trans-18 : 1n-9 and trans-18 : 2n-6n-9), which were detected in the whole blood, serum and erythrocyte membranes of each subject. The TFA index and the 10-year CHD RP were compared by linear models. It was shown that only in the erythrocyte membrane, the TFA isomers were significantly different between the groups. In the ACS group, industry-generated TFA (trans-16 : 1n-9, trans-18 : 1n-9 and trans-18 : 2n-6n-9) were the highest, whereas ruminant-originated TFA (trans-16 : 1n-7 and trans-18 : 1n-7), which manifested an inverse relationship with CHD, were the lowest, and vice versa in the HV group. The TFA index decreased progressively from 7·12 to 5·06, 3·11 and 1·92 in the ACS, CCAD, HRP and HV groups, respectively. The erythrocyte membrane TFA index was positively associated with the 10-year CHD RP (R 2 0·9981) and manifested a strong linear correlation, which might reflect the true pathological severity of CHD.
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Enfermedad Coronaria/epidemiología , Membrana Eritrocítica/química , Ácidos Grasos/sangre , Probabilidad , Anciano , Estudios de Casos y Controles , Enfermedad Coronaria/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
This study was conducted to investigate the current contamination status of polyhalogenated aromatic hydrocarbons (PHAHs) in sediments from the mainstream and 22 primary tributaries of the Yangtze River in the Three Gorges Reservoir region. To accomplish this, the concentrations of 22 polybrominated biphenyl (PBB) congeners, 27 polybrominated diphenyl ether (PBDE) congeners, and 27 polychlorinated biphenyl (PCB) congeners in sediment samples were measured by GC-MS/MS. The result showed that the observed values of PBBs and PBDEs were 22.41 and 35.24 pg g(-1) dw, respectively. PBB1, 31 and 103 were the predominant PBB congeners, while PBDE28, 47, 77 and 99 were the predominant PBDE congeners. PBB209 and BDE209 were detected in >39% of the samples, with geometric means 2.43 and 11.92 pg g(-1) dw, respectively. PCBs were found to be the predominant compounds in sediment samples among the three PHAH subfamilies, with a geometric mean of 1,231.11 pg g(-1) dw, and PCB8, 18, 28, 52 and 66 were the primary PCB congeners. The measured levels of PHAHs were compared with results recently reported in the literature and their respective sediment quality guidelines recommended by the USEPA. The levels of PHAHs in the present study were generally lower than their respective threshold-effect levels, or were comparable to those reported in relatively uncontaminated freshwater samples from other regions. Taken together, these results suggest that, in the reservoir, toxic biological effects on aquatic biota in response to PHAHs contamination of sediments can be expected to be negligible.
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Agua Dulce/análisis , Sedimentos Geológicos/análisis , Éteres Difenilos Halogenados/análisis , Bifenilos Polibrominados/análisis , Bifenilos Policlorados/análisis , Contaminantes Químicos del Agua/análisis , China , Cromatografía de Gases , Monitoreo del Ambiente , Espectrometría de Masas en TándemRESUMEN
Lotus root (LR) is prone to browning after harvest due to the oxidation of phenolic compounds by polyphenol oxidase (PPO). This study compared the effects of LR extract and BLR extract on cholesterol metabolism in high-fat diet (HFD) mice. Our findings highlighted the innovative potentiality of BLR extract in effectively regulating cholesterol metabolism via inhibiting the intestinal FXR-FGF15 signaling pathway and boosting probiotics in gut microbiota, offering valuable insights for hypercholesterolemia and metabolic disorders. In detail, catechin was the main phenolic compound in LR, while after browning, theaflavin was the main oxidation product of phenolic compounds in BLR. Both the intake of LR extract and BLR extract regulated the disorder of cholesterol metabolism induced by HFD. In particular, BLR extract intake exhibited more robust effects on increasing the BAs contents synthesized in the liver and excreted in feces compared with LR extract intake. Furthermore, the consumption of BLR extract was more effective than that of LR extract in reducing the ileal protein expressions of FXR and FGF15 and shifting BAs biosynthesis from the classical pathway to the alternative pathway. Moreover, LR extract and BLR extract had distinct effects on the gut microbiota in HFD-fed mice: BLR extract significantly elevated probiotics Akkermansia abundance, while LR extract increased Lactobacillus abundance. Therefore, both LR extract and BLR extract improved the cholesterol deposition effectively and BLR extract even showed a stronger effect on regulating key gene and protein expressions of cholesterol metabolism.
RESUMEN
Polyphenol oxidase (PPO) causes the browning of lotus roots (LR), negatively affecting their nutrition and shelf-life. This study aimed to explore the specific selectivity of PPO toward polyphenol substrates, thus unlocking the browning mechanism of fresh LR. Results showed that two highly homologous PPOs were identified in LR and exhibited the highest catalytic activity at 35 â and pH 6.5. Furthermore, the substrate specificity study revealed (-)-epigallocatechin had the lowest Km among the polyphenols identified in LR, while (+)-catechin showed the highest Vmax. The molecular docking further clarified that (-)-epigallocatechin exhibited lower docking energy and formed more hydrogen bonds and Pi-Alkyl interactions with LR PPO than (+)-catechin, while (+)-catechin entered the active cavity of PPO more quickly due to its smaller structure, both of which enhance their affinity to PPO. Thus, (+)-catechin and (-)-epigallocatechin are the most specific substrates responsible for the browning mechanism of fresh LR.
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Catequina , Nelumbo , Polifenoles , Nelumbo/metabolismo , Simulación del Acoplamiento Molecular , Catecol Oxidasa/metabolismo , Especificidad por SustratoRESUMEN
Browning of fresh-cut plants is mainly attributed to the enzymatic browning of phenolic compounds induced by polyphenol oxidase (PPO), producing browning products such as anthraquinones, flavanol oxides, and glycosides, which are usually considered to be non-toxic. Could browning bring any benefits on behalf of their bioactivity? Our previous study found that browned lotus root extracts (BLREs) could reduce the cholesterol level in obese mice as fresh lotus root extracts (FLREs) did. This study aimed to compare the mechanisms of FLRE and BLRE on cholesterol metabolism and verify whether the main component's monomer regulates cholesterol metabolism like the extracts do through in vitro experiments. Extracts and monomeric compounds are applied to HepG2 cells induced by free fatty acids (FFA). Extracellular total cholesterol (TC) and triglyceride (TG) levels were also detected. In addition, RT-PCR and Western blot were used to observe cholesterol metabolism-related gene and protein expression. The in vitro results showed that BLRE and FLRE could reduce TC and TG levels in HepG2 cells. In addition, BLRE suppressed the synthesis of cholesterol. Meanwhile, FLRE promoted the synthesis of bile acid (BA) as well as the clearance and efflux of cholesterol. Furthermore, the main monomers of BLRE also decreased cholesterol synthesis, which is the same as BLRE. In addition, the main monomers of FLRE promoted the synthesis of BAs, similar to FLRE. BLRE and FLRE promote cholesterol metabolism by different pathways.
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Phospholipids play a crucial role in the growth and neurodevelopment of infants. Currently, soybean phospholipids (SPLs) are the common phospholipid component in most infant formulas (IFs), which, however, shows an obvious difference with the phospholipid (PL) composition of human milk fat. Therefore, in the present study, human milk phospholipid analogs (HMPAs) were prepared by mimicking the composition of PE, PC, PI, PS, and SM in breast milk phospholipids and the composition of the major fatty acids (C16:0, C18:0, C18:1, and C18:2), and their digestion and absorption characteristics were explored using in vitro and mice models. The prepared HMPA contained 26.48% PE, 24.64% PC, 36.19% SM, 6.35% PI, and 6.32% PS, with 40.51% C16:0, 17.02% C18:0, 29.19% C18:1, and 13.26% C18:2, showing different digestive properties relative to SPL. There was little effect on the physical and chemical properties of HMPA under in vitro gastric conditions. The hydrolysis degree, fatty acids release rate, and average particle size decreasing rate of HMPA was significantly higher than that of SPL during digestion in vitro intestine (P < 0.05), showing better digestive process relative to SPL. In terms of the mice model, HMPA had a higher hydrolysis degree in the intestinal tract. Based on the area under curve (AUC) analysis of serum fatty acids, it was found that despite HMPA being absorbed at a slower rate than SPL, it was absorbed more than SPL. In summary, the digestion and absorption of HMPA were preferred to SPL, and these obtained results might provide a theoretical basis for the development and utilization of HMPA in IF.
Asunto(s)
Leche Humana , Fosfolípidos , Femenino , Lactante , Humanos , Ratones , Animales , Fosfolípidos/análisis , Leche Humana/química , Hempa/análisis , Ácidos Grasos/análisis , Leche/química , DigestiónRESUMEN
Inspired by the brilliant and tunable structural colors based on the large refractive index contrast (Δn) and non-close-packing structures of chameleon skins, ZnS-silica photonic crystals (PCs) with highly saturated and adjustable colors are fabricated. Due to the large Δn and non-close-packing structure, ZnS-silica PCs show 1) intense reflectance (maximal: 90%), wide photonic bandgaps, and large peak areas, 2.6-7.6, 1.6, and 4.0 times higher than those of silica PCs, respectively; 2) tunable colors by simply adjusting the volume fraction of particles with the same size, more convenient than the conventional way of altering particle sizes; and 3) a relatively low threshold of PC's thickness (57 µm) possessing maximal reflectance compared to that (>200 µm) of the silica PCs. Benefiting from the core-shell structure of the particles, various derived photonic superstructures are fabricated by co-assembling ZnS-silica and silica particles into PCs or by selectively etching silica or ZnS of ZnS-silica/silica and ZnS-silica PCs. A new information encryption technique is developed based on the unique reversible "disorder-order" switch of water-responsive photonic superstructures. Additionally, ZnS-silica PCs are ideal candidates for enhancing fluorescence (approximately tenfold), approximately six times higher than that of silica PC.
RESUMEN
Mercury (Hg2+) is one of the most toxic heavy metals in farm products, so rapid detection of trace Hg2+ has always been sought after with high interest. Herein, we report a biosensor to specifically recognize Hg2+ in leaching solutions of brown rice flour. This sensor is simple and of low cost, with a very short assay time of 30 s. Another merit is the ultra-low limit of detection (LOD) at fM level. In addition, the specific aptamer probe realizes a good selectivity above 105: 1 against the interferences. This sensor is developed based on an aptamer-modified gold electrode array (GEA) for capacitive sensing. Alternating current electrothermal (ACET) enrichment is induced during the AC capacitance acquirement. Thus, the enrichment and detection are coupled as a single step, and pre-concentration is needless. Owing to the sensing mechanism of solid-liquid interfacial capacitance and ACET enrichment, Hg2+ level can be sensitively and rapidly reflected. Also, the sensor has a wide linear range from 1 fM to 0.1 nM and a shelf life of 15 days. This biosensor shows advantages on overall performance, enabling easy-to-operate, real-time, and large-scale Hg2+ detection in farm products.
Asunto(s)
Técnicas Biosensibles , Mercurio , Oryza , Harina , Oro , Límite de Detección , OligonucleótidosRESUMEN
Tribovoltaic nanogenerators (TVNGs) have the characteristics of high current density, low matched impedance and continuous output, which is expected to solve the problem of power supply for small electronic devices. However, wear occurrence in friction interface will seriously reduce the performance of TVNGs as well as lifetime. Here, we employ MXene solution as lubricate to improve output current density and lifetime of TVNG simultaneously, where a high value of 754 mA m-2 accompanied with a record durability of 90,000 cycles were achieved. By comparing multiple liquid lubricates with different polarity, we show that conductive polar liquid with MXene as additive plays a crucial role in enhancing the electrical output performance and durability of TVNG. Moreover, the universality of MXene solution is well demonstrated in various TVNGs with Cu and P-type Si, and Cu and N-GaAs as material pairs. This work may guide and accelerates the practical application of TVNG in future.
RESUMEN
The study explored the effects of Angelica sinensis extract (AsE) on oxidative lesions and apoptosis in branchiae and red blood corpuscles in hypoxia-reoxygenation (HR) and Cu-treated carp (Cyprinus carpio var. Jian). After feeding trial for 30 days, the carp were exposed to HR and CuSO4. The results indicated that dietary AsE increased the durative time, decreased the oxygen consumption rate, suppressed ROS generation and cellular component oxidation, decreased enzymatic antioxidant activity and reduced glutathione (GSH) levels in red blood corpuscles and branchiae in carp under hypoxia. Moreover, dietary AsE avoided the loss of Na+,K+-ATPase, metabolic and antioxidant enzyme activities, ROS generation and cellular component oxidation, as well as the increase in caspase-8, 9, and 3 activities in the branchiae of the carp and inhibited ROS generation. It furthermore avoided the loss of Na+,K+-ATPase and metabolic enzyme activities, the decrease in GSH levels and hemoglobin content, the increase in the activities of caspase-8, 9, and 3 and the increase in the levels of cytochrome c and phosphatidylserine exposure in the red blood corpuscles of Cu-exposed carp. The present results suggested that dietary AsE improved hypoxia tolerance and inhibited HR or Cu-triggered oxidative lesions and apoptosis. Therefore, AsE can be utilized as a natural inhibitor of Cu and HR stress in fish.