Naringenin (NN) is one of the most abundant flavonoids in citrus and grapefruits and has been shown to have antioxidant properties in vitro. The purpose of the study is to examine the antioxidant and anti-aging activities of NN in C. elegans, and to further explore the molecular mechanism. The results showed that NN enhanced the lifespan under normal and oxidative stress induced by H2O2. After treatment with NN, locomotion capability was improved and aging pigment accumulation was suppressed. NN also delayed the paralysis and reversed the defective chemotaxis behavior induced by Aβ protein. Meanwhile, the treatment with NN enhanced the activities of antioxidant enzymes and reduced the accumulation of reactive oxygen species (ROS) and malondialdehyde (MDA) content. The possible targets and pathways interacting with NN were predicted by network pharmacology. Real-time PCR analysis indicated that NN upregulated the expression levels of daf-16, sek-1 and skn-1, downregulated the expression levels of daf-2, age-1 and akt-1, and further activated sod-3, ctl-1, ctl-2, gst-4 and mtl-1. Moreover, the selected mutant strains were used and molecular docking was conducted to further suggest that IIS and MAPK pathways could be involved in the NN-mediated longevity-promoting effect.
Hyperoside, the main component of many anti-obesity plants, might exhibit a lipase inhibition effect to reduce fat accumulation. The anti-obesity effect of hyperoside was investigated by studying its inhibitory effect and mechanism on pancreatic lipase in vitro and evaluating its ability to reduce lipid accumulation in vivo. Hyperoside is a mixed-type inhibitor of lipase with an IC50 of 0.67 ± 0.02 mmol L-in vitro. Hyperoside changed the secondary conformation of lipase, increased the α-helix content, and changed the microenvironment of lipase through static quenching. The interaction between hyperoside and lipase results from a strong binding spontaneous exothermic reaction, mainly through hydrogen bonding, van der Waals force and electrostatic force. Hyperoside protected hepatic lipid accumulation and adipose tissue hypertrophy and reduced the expression of inflammatory factors in high-fat diet-induced rats. Moreover, hyperoside had a good inhibitory effect on lipase activity in serum and increased fecal fat excretion, thereby reducing lipid absorption in vivo. This study provides theoretical support for the research and development of hyperoside in fat-reducing functional foods.
Background: Brucella is the pathogen of brucellosis, a prevalent zoonotic infectious disease in the world, it mainly resides in macrophages after invading the body.Methods: In order to determine the relationship between brucella and two types of macrophages in the lesion sites of brucella spondylitis, the distribution of brucella, the expression levels of iNOS, Arg1 and Cx3cr1 in paravertebral cartilage and connective tissue of 40 brucella spondylitis patients were detected by immunohistochemistry. In addition to clear the relationship between cytokines in peripheral blood and macrophage polarization, the level IL-12, IL-10, TGF-β, INF-γ and INOS, Arg-1 in peripheral blood of patients were detected by ELISA.Results: A large number of brucella and high expression of Cx3cr1 and Arg-l exist in cartilage and connective tissue adjacent of lesions of brucella spondylitis patients and the molecular Arg-1, IL-10, TGF-βwere significantly higher than that of control group in peripheral blood of brucella spondylitis patients. Thus it can be seen the M2 macrophages and the relevant cytokines IL-10 and TGF-βis given priority to the immune response whether local or systemic immune of brucella spondylitis patients.Conclusion: We speculate that immune regulation could be enhance the ability of the body to remove pathogens and adjuvant treatment of brucella disease by inducing macrophages to M1-type in brucella spondylitis patients.
Rationale: Receptor for advanced glycation end products (RAGE) is implicated in inflammatory responses in acute respiratory distress syndrome (ARDS) /acute lung injury (ALI), but its role in pulmonary edema formation remains unclear. Hence, we aim to explore potential mechanisms of RAGE signaling in ALI-related impaired alveolar fluid clearance (AFC). Methods: Serum and Bronchial Alveolar Lavage Fluid (BALF) samples were obtained from 11 ARDS patients and 10 healthy volunteers. Soluble RAGE (sRAGE) and albumin (ALB) levels were measured by ELISA, and the ratio of BALF and serum ALB (B/S) was defined as an indicator of pulmonary vascular permeability. ARDS mouse model was established by LPS intratracheal instillation in wide-type (WT) mice and RAGE knockout (KO) mice. AFC was determined by the change of FITC-labeled BSA instilled in the lung, and Na-K-ATPase and ENaC expressions were evaluated by Western-blot. Results: BALF sRAGE and B/S in ARDS patients was much higher than those in healthy volunteers (1004.74±1219.72vs.163.55±120.11 pg/ml; 5.60±7.73vs.0.40±0.31‰), and BALF sRAGE was positively related to B/S. In animal study, LPS markedly increased BALF sRAGE and B/S levels, whereas significantly decreased AFC; BALF sRAGE was negatively related to AFC but positively related to B/S. All the effects of LPS were alleviated in KO mice (AFC: 14.43±4.76vs.6.82±2.31%; B/S: 5.37±2.75vs.9.42±0.47‰). BALF sRAGE was undetectable in KO mice. Moreover, LPS-induced downregulation of Na-K-ATPase and ENaC was prevented by RAGE depletion. Conclusions: Our findings imply that RAGE is involved in impaired AFC by regulating Na-K-ATPase and ENaC expression in ALI/ARDS.
Blue honeysuckle rich in anthocyanins can inhibit starch-digesting enzyme activity. This study evaluated the inhibitory effect and mechanism of blue honeysuckle extract (BHE) on glycosidases (α-amylase and α-glucosidase). BHE was a mixed glycosidase inhibitor with an IC50 of 2.36 ± 0.14 and 0.06 ± 0.01 for α-amylase and α-glucosidase, respectively. Fourier transform infrared (FTIR) spectroscopy, multi-fluorescence spectroscopy, and isothermal titration calorimetry (ITC) confirmed that BHE caused the secondary structure change and static fluorescence quenching of glycosidases, and the interaction was an enthalpy-driven exothermic reaction. Molecular docking proved that the main anthocyanin monomers in BHE interacted with glycosidases through hydrogen bonds and van der Waals forces. Moreover, BHE changed the starch structure and prevented starch from being digested by glycosidases. In vivo, BHE and starch-BHE complexes effectively slowed postprandial hyperglycemia. This research provided a theoretical basis for BHE in antidiabetic healthy food research and development.
Objective
To explore the value of conventional echocardiography and transthoracic real-time three-dimensional echocardiography (RT3DE) in diagnosis of Ebstein anomaly.
Methods
We investigated the morphology and function of right ventricle (RV) as well as the structure, morphology and regurgitation of tricuspid valve in 61 adult patients with Ebstein anomaly before surgery by using conventional echocardiography and transthoracic RT3DE. Twenty normal adults were enrolled as control group.
Results
The surface of the tricuspid leaflets, the morphology of the tricuspid annulus as well as the three-dimensional structure of the tricuspid valve were displayed stereoscopically by RT3DE. Complete RV volume data could be acquired in 32 patients of Ebstein anomaly. The apex or part of RV could not be contained in the remaining 29 patients. Thirty-four (55.7%) patients with Ebstein anomaly had severe tricuspid regurgitation, 16 (26.2%) patients had moderate to severe regurgitation, and 11 (18.1%) patients had moderate regurgitation. Compared with the normal adults, patients of Ebstein anomaly showed higher RV end-diastolic volume (EDV), end-systolic volume (ESV), end-diastolic volume index (EDVI), end-systolic volume index (ESVI), stroke volume (SV), RV anterior-posterior diameter (RV), tricuspid valve annular transverse diameter (TV-R), and lower RV ejection fraction(EF) [(273.5±77.7) ml vs (74.3±15.9) ml, (187.1±96.8) ml vs (31.1±9.2) ml, (177.4±53.6) ml/m2vs (43.4±8.2) ml/m2, (121.7±65.5) ml/m2vs (18.4±5.1) ml/m2, (95.9±20.2) ml vs (43.6±8.8) ml, (48.1±13.3) ml/m2vs (19.0±1.9) ml/m2, (56.4±8.9) ml/m2vs (28.5±4.3) ml/m2, (38.3±12.8) % vs (59.3±5.1) %, all P<0.05). The tricuspid regurgitant orifice flow cross-sectional area (EROA) were correlated positively with RV anterior-posterior diameter (r=0.691), ratio of RV and LV anterior-posterior diameter (RV/LV) (r=0.6471).
Conclusion
Transthoracic RT3DE is a feasible method in addition to conventional two-dimensional echocardiography in evaluation of tricuspid valve mophology and function, as well as RV volume and EF in adult patients with Ebstein anomaly.
Key words:
Echocardiography, three-Dimensional; Tricuspid valve; Heart diseases
Metabolic (dysfunction)-associated steatohepatitis (MASH) is the advanced stage of metabolic (dysfunction)-associated fatty liver disease (MAFLD) lacking approved clinical drugs. Adenosine A1 receptor (A1R), belonging to the G-protein-coupled receptors (GPCRs) superfamily, is mainly distributed in the central nervous system and major peripheral organs with wide-ranging physiological functions; however, the exact role of hepatic A1R in MAFLD remains unclear. Here, we report that liver-specific depletion of A1R aggravates while overexpression attenuates diet-induced metabolic-associated fatty liver (MAFL)/MASH in mice. Mechanistically, activation of hepatic A1R promotes the competitive binding of sterol-regulatory element binding protein (SREBP) cleavage-activating protein (SCAP) to sequestosome 1 (SQSTM1), rather than protein kinase A (PKA) leading to SCAP degradation in lysosomes. Reduced SCAP hinders SREBP1c/2 maturation and thus suppresses de novo lipogenesis and inflammation. Higher hepatic A1R expression is observed in patients with MAFL/MASH and high-fat diet (HFD)-fed mice, which is supposed to be a physiologically adaptive response because A1R agonists attenuate MAFL/MASH in an A1R-dependent manner. These results highlight that hepatic A1R is a potential target for MAFL/MASH therapy.
The present study aimed to investigate whether C‑X‑C motif chemokine receptor 3 (CXCR3) and its ligands may aid in diagnosing spinal tuberculosis (ST). A total of 36 patients with ST and 20 healthy controls were enrolled in the present study. The morphology of tuberculous granuloma in spinal tissue was observed by hematoxylin and eosin staining. The presence and distribution of acid‑fast bacilli (AFB) were observed by Ziehl‑Neelsen (ZN) staining. The protein expression of Ag85B, IFN‑γ, and CXCR3 and its ligands (CXCL9 and CXCL10) were detected by immunohistochemistry. The levels of IFN‑γ, CXCR3, CXCL9 and CXCL10 in peripheral blood of patients with ST and healthy controls were detected by reverse transcription‑quantitative polymerase chain reaction and ELISA. Typical tuberculous granuloma was observed in the ST close tissue. AFB was observed by ZN staining. Positive expression of Ag85B was found in the surrounding caseous necrotic tissue of the tuberculous granuloma. IFN‑γ, CXCR3, CXCL9 and CXCL10 were expressed in the tissue surrounding the tuberculous granuloma and their expression levels were markedly higher than those in the distant tissues. The levels of IFN‑γ, CXCR3, CXCL9 and CXCL10 in peripheral blood of patients with ST were significantly higher than those in the healthy controls. Receiver operating characteristic curve analysis demonstrated that IFN‑γ, CXCR3 and CXCL10 were more reliable diagnostic markers in terms of sensitivity and specificity. IFN‑γ, CXCR3, CXCL9 and CXCL10 were highly expressed in the lesion tissue and peripheral blood samples of patients with ST, and IFN‑γ, CXCR3 and its ligands aided in diagnosing ST.
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