Gas chromatography ion mobility spectroscopy: A rapid and effective tool for monitoring oil oxidation.

Oil autoxidation is an early process of food deterioration, monitoring oil oxidation is therefore of great significance to ensure food quality and safety. In this study, a detection method of the primary and secondary oxidative products was developed by gas chromatography ion mobility spectrometry (GC-IMS).The secondary oxidative products was analyzed by GC-IMS. Then, the relationships between peroxide values and the contents of secondary oxidative products were investigated by constructing a prediction model of peroxide value of rapeseed oil with the help of secondary oxidative products and chemometrics. The coefficient of determination Q2 of the model validation set is 0.96, and the RMSECV is 0.1570 g/100 g. These validation results indicated that secondary oxidative products could also reflect the content of the primary oxidative products. Moreover, 10 characteristic markers related to oxidative rancidity were identified for monitoring edible oil rancidity and oxidative stability.

Licochalcone A regulates viral IRES activity to inhibit enterovirus replication.

Enterovirus D68 (EV-D68), belonging to the genus Enterovirus of the Picornavirus family, is an emerging pathogen that can cause neurological and respiratory diseases in children. However, there is little understanding of the pathogenesis of EV-D68, and no effective vaccine or drug for the prevention or treatment of the diseases caused by this virus is available. Autophagy is a cellular process that targets cytoplasmic proteins or organelles to the lysosomes for degradation. Enteroviruses strategically harness the host autophagy pathway to facilitate the completion of their life cycle. Therefore, we selected an autophagy compound library to screen for autophagy-related compounds that may affect viral growth. By using the neutralization screening assay, we identified a compound, 'licochalcone A' that significantly inhibited EV-D68 replication. To investigate the mechanism by which licochalcone A inhibits EV-D68 replication and to identify the viral life cycle stage it inhibits, the time-of-addition, viral attachment, viral entry, and dual-luciferase reporter assays were performed. The results of the time-of-addition assay showed that licochalcone A, a characteristic chalcone found in liquorice roots and widely used in traditional Chinese medicine, inhibits EV-D68 replication during the early stages of the viral life cycle, while those of the dual-luciferase reporter assay showed that licochalcone A does not regulate viral attachment and entry, but inhibits EV-D68 IRES-dependent translation. Licochalcone A also inhibited enterovirus A71 and coxsackievirus B3 but did not significantly inhibit dengue virus 2 or human coronavirus 229E replication. Licochalcone A regulates IRES translation to inhibit EV-D68 viral replication.

Uncovering Mechanism and Efficacy of Salvia Miltiorrhiza-Safflower in Cerebral Ischemia-Reperfusion Injury.

Cerebral ischemia (CI) is the main cause of stroke morbidity and disability. This study aims to identify the early molecular regulation responsible for the therapeutic effectiveness of the Herb pair Danshen-Honghua (DH) for CI. The major targets of DH were identified by searching the public database of traditional Chinese medicine (TCM). In addition, GeneCards, Disgenet, and GeneMap databases in OMIM were used to determine the disease targets of CI. A total of 88 common targets of DH and CI were selected, a protein-protein interaction (PPI) network was established by Cytoscape, and 19 core targets were screened. These genes were primarily enriched in biological processes including wound healing, reaction to oxidative stress, and response to peptides, lipid and atherosclerosis, Age-rage signaling pathway, and TNF signaling pathway by KEGG and GO enrichments. The effective components of DH had stable binding to these key targets by molecular docking. Finally, it was verified that the mechanism of DH on CI treatment may be related to the activation of the TNF-α/JNK signaling pathway by establishing the middle cerebral artery occlusion (MCAO) rat model.

The role of Ginkgo Folium on antitumor: Bioactive constituents and the potential mechanism.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginkgo biloba L. is a well-known and highly regarded resource in Chinese traditional medicine due to its effectiveness and safety. Ginkgo Folium, the leaf of Ginkgo biloba L., contains biologically active constituents with diverse pharmacological activities. Recent studies have shown promising antitumor effects of the bioactive constituents found in Ginkgo Folium against various types of cancer cells, highlighting its potential as a natural source of antitumor agents. Further research is needed to elucidate the underlying mechanisms and optimize its therapeutic potential. AIM OF THE REVIEW: To provide a detailed understanding of the pharmacological activities of Ginkgo Folium and its potential therapeutic benefits for cancer patients. MATERIALS AND METHODS: In this study, we conducted a thorough and systematic search of multiple online databases, including PubMed, Web of Science, Medline, using relevant keywords such as "Ginkgo Folium," "flavonoids," "terpenoids," "Ginkgo Folium extracts," and "antitumor" to cover a broad range of studies that could inform our review. Additionally, we followed a rigorous selection process to ensure that the studies included in our review met the predetermined inclusion criteria. RESULTS: The active constituents of Ginkgo Folium primarily consist of flavonoids and terpenoids, with quercetin, kaempferol, isorhamnetin, ginkgolides, and bilobalide being the major compounds. These active constituents exert their antitumor effects through crucial biological events such as apoptosis, cell cycle arrest, autophagy, and inhibition of invasion and metastasis via modulating diverse signaling pathways. During the process of apoptosis, active constituents primarily exert their effects by modulating the caspase-8 mediated death receptor pathway and caspase-9 mediated mitochondrial pathway via regulating specific signaling pathways. Furthermore, by modulating multiple signaling pathways, active constituents effectively induce G1, G0/G1, G2, and G2/M phase arrest. Among these, the pathways associated with G2/M phase arrest are particularly extensive, with the cyclin-dependent kinases (CDKs) being most involved. Moreover, active constituents primarily mediate autophagy by modulating certain inflammatory factors and stressors, facilitating the fusion stage between autophagosomes and lysosomes. Additionally, through the modulation of specific chemokines and matrix metalloproteinases, active constituents effectively inhibit the processes of epithelial-mesenchymal transition (EMT) and angiogenesis, exerting a significant impact on cellular invasion and migration. Synergistic effects are observed among the active constituents, particularly quercetin and kaempferol. CONCLUSION: Active components derived from Ginkgo Folium demonstrate a comprehensive antitumor effect across various levels and pathways, presenting compelling evidence for their potential in new drug development. However, in order to facilitate their broad and adaptable clinical application, further extensive experimental investigations are required to thoroughly explore their efficacy, safety, and underlying mechanisms of action.

Maimendong decoction regulates M2 macrophage polarization to suppress pulmonary fibrosis via PI3K/Akt/FOXO3a signalling pathway-mediated fibroblast activation.

ETHNOPHARMACOLOGICAL RELEVANCE: Mai Men Dong decoction (MMDD), a traditional Chinese medicine formula, is relevant to ethnopharmacology due to its constituents and therapeutic properties. The formula contains herbs like Ophiopogon japonicus (Thunb.) Ker Gawl., Pinellia ternata (Thunb.) Makino, Panax ginseng C.A.Mey, Glycyrrhiza uralensis Fisch, and Ziziphus jujuba Mill, Oryza sativa L., which have been used for centuries in Chinese medicine. These herbs provide a comprehensive approach to treating respiratory conditions by addressing dryness, cough, and phlegm. Ethnopharmacological studies have explored the scientific basis of these herbs and identified active compounds that contribute to their medicinal effects. The traditional usage of MMDD by different ethnic groups reflects their knowledge and experiences. Examining this formula contributes to the understanding and development of ethnopharmacology. AIM OF THE STUDY: In the case of pulmonary fibrosis (PF), treating it can be challenging due to the limited treatment options available. This study aimed to assess the potential of MMDD as a treatment for PF by targeting macrophages and the PI3K/Akt/FOXO3a signaling pathway. MATERIALS AND METHODS: In a mouse model of PF, we investigated the effects of MMDD on inflammation, fibrosis, and M2 macrophage infiltration in lung tissue. Additionally, we examined the modulation of pro-fibrotic factors and key proteins in the PI3K/Akt/FOXO3a pathway. In vitro experiments involved inducing M2-type macrophages and assessing the impact of MMDD on fibroblast activation and the PI3K/Akt/FOXO3a pathway. RESULTS: Results demonstrated that MMDD improved weight, reduced inflammation, and inhibited M2 macrophage infiltration in mouse lung tissue. It downregulated pro-fibrotic factors, such as TGF-ß1 and PDGF-RB, as well as markers of fibroblast activation. MMDD also exhibited regulatory effects on key proteins in the PI3K/Akt/FOXO3a signaling pathway. CONCLUSIONS: MMDD inhibited M2 macrophage polarization and released profibrotic factors that inhibited pulmonary fibrosis. As a result, the PI3K/Akt/FOXO3a signaling pathway is suppressed. MMDD is proving to be a successful treatment for PF. However, further research is needed to validate its effectiveness in clinical practice.

Areca Thirteen Pill Improves Depression in Rat by Modulation of the Chemokine/Chemokine Receptor Axis.

Depressive disorder is a severe and complex mental illness. There are a few anti-depressive medications that can reduce depressive symptoms, but with adverse or side effects. GaoYou-13 (GY-13), commonly known as Areca Thirteen Pill, is a traditional medicine for depression treatment with significant clinical impact. However, the molecular mechanism of GY-13 has not been fully elucidated. This study aimed to explore and explain the action and mechanism of GY-13 in treatment for depression. SD male rats were stimulated differently daily for 42 days to construct a depression rat model and divided into six groups: the control, CUMS model, GY-13L, GY-13 M, GY-13H, and FLUO. The body weight of was measured on day 7, 14, 21, 28, 35, and 42 or different days, and the behavioral tests (Open-field test, Sucrose preference test, Morris water maze) were made alongside. After the rats were decapitated, the rat brains were stained with Nissl or H&E dyes. The serums of TNF-α and IL-1ß were tested. The protein of p-IKKα, p-IкBα, and p-NFкBp65 was traced. Then nano-LC-MS/MS analysis was made to detect the mechanism of GY-13. The active ingredients, drug targets, and key pathways of GY-13 in treating depression were analyzed through network pharmacology and molecular docking. With immunohistochemistry, quantitative RT-PCR, and western-blot techniques, the therapeutic mechanism of GY-13 was traced and analyzed. This study revealed that GY-13 significantly enhances autonomous and exploratory behavior, sucrose consumption, learning and memory ability, and hippocampal neuronal degeneration, which inhibits inflammation. In addition, omics analysis showed several proteins were altered in the hippocampus of rats following CUMS and GY-13 treatment. Bioinformatics analysis and network pharmacology revealed the antidepressant effects of GY-13 are related to the chemokine/chemokine receptor axis. Immunohistochemistry, western blotting and RT-PCR assay further support the findings of omics analysis. We highlighted the importance of the chemokine/chemokine receptor axis in the treatment of depression, as well as showed GY-13 can be used as a novel targeted therapy for depression treatment.

Diagnostic Significance of DCE-MRI-Related Quantitative Parameters for Nasal Cavity and Sinus Tumors.

Objective: Our aim was to explore the diagnostic value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)-related quantitative parameters for benign and malignant nasal cavity and sinus tumors. Methods: A total of 78 patients with nasal sinus tumors admitted to People's Hospital of Qingdao Chengyang District in China were enrolled in our study, Of the patients, 41 were diagnosed as having benign tumors and 37 as having malignant tumors by pathological diagnosis. All patients received DCE-MRI scans before surgery to derive time-intensity curves (TICs) and related quantitative parameters (flux rate constant [Kep], transfer constant [Ktrans], extravascular volume fraction [Ve]). The diagnostic surgical pathology results were used as the gold standard to analyze the diagnostic effect of TIC and related quantitative parameters of DCE-MRI, and the receiver operating characteristic (ROC) curves were plotted to determine the values of each parameter in predicting nasal sinus tumors. Results: The percentage of class I in the benign group was significantly higher than in the malignant group (P < .05); the percentage of class III in the benign group was significantly lower than in the malignant group (P < .05); the percentage of class II in the 2 groups was comparable (P > .05). Kep, Ktrans and Ve in the benign group were 0.338±0.124, 0.061±0.035 and 0.532±0.138, respectively; Kep, Ktrans and Ve in the malignant group were 0.785±0.211, 0.441±0.125 and 0.327±0.048, respectively. The levels of Kep and Ktrans were significantly lower in the benign group than in the malignant group (all P < .05); the levels of Ve were significantly higher in the benign group than in the malignant group (P < .05). The optimal Kep cut-off value for predicting malignant nasal sinus tumors was 0.510 min-1, with a sensitivity of 81.4% and specificity of 89.5%; the optimal Ktrans cut-off value for predicting malignant nasal sinus tumors was 0.206 min-1, with a sensitivity of 84.3% and specificity of 89.7%; the optimal Ve cut-off value for predicting malignant nasal sinus tumors was 0.384 min-1, with a sensitivity of 71.8% and specificity of 82.4%. Conclusion: DCE-MRI-related quantitative parameters are ideal for the diagnosis of benign and malignant nasal sinus tumors. This modality provides more data for the identification of the nature of the tumor, and thus merits clinical promotion and application.

The biosynthesis, degradation, and function of cell wall ß-xylosylated xyloglucan mirrors that of arabinoxyloglucan.

Xyloglucan is an abundant polysaccharide in many primary cell walls and in the human diet. Decoration of its α-xylosyl sidechains with further sugars is critical for plant growth, even though the sugars themselves vary considerably between species. Plants in the Ericales order - prevalent in human diets - exhibit ß1,2-linked xylosyl decorations. The biosynthetic enzymes responsible for adding these xylosyl decorations, as well as the hydrolases that remove them in the human gut, are unidentified. GT47 xyloglucan glycosyltransferase candidates were expressed in Arabidopsis and endo-xyloglucanase products from transgenic wall material were analysed by electrophoresis, mass spectrometry, and nuclear magnetic resonance (NMR) spectroscopy. The activities of gut bacterial hydrolases BoGH43A and BoGH43B on synthetic glycosides and xyloglucan oligosaccharides were measured by colorimetry and electrophoresis. CcXBT1 is a xyloglucan ß-xylosyltransferase from coffee that can modify Arabidopsis xyloglucan and restore the growth of galactosyltransferase mutants. Related VmXST1 is a weakly active xyloglucan α-arabinofuranosyltransferase from cranberry. BoGH43A hydrolyses both α-arabinofuranosylated and ß-xylosylated oligosaccharides. CcXBT1's presence in coffee and BoGH43A's promiscuity suggest that ß-xylosylated xyloglucan is not only more widespread than thought, but might also nourish beneficial gut bacteria. The evolutionary instability of transferase specificity and lack of hydrolase specificity hint that, to enzymes, xylosides and arabinofuranosides are closely resemblant.

Enhanced Yield of Bioactive Compounds and Antioxidant Activities in Four Fermented Beans of Phellinus linteus Strains (Agaricomycetes) by Solid-State Fermentation.

Phellinus linteus is a famous medicinal mushroom which exhibits various biological activities. This study aimed to investigate the effects of solid-state fermentation by Ph. linteus on the yield of bioactive compounds and antioxidant activities of beans. Four bean substrates were prepared and inoculated with inoculum of three strains of Ph. linteus, respectively. During the cultivation, the harvested samples were dried, grounded, extracted, and determined the contents of bioactive compounds and antioxidant activities. The results indicated that the mung bean fermented by Ph. linteus 04 had the highest polysaccharide content (98.8 mg/g). The highest total phenolic and flavonoid contents were in fermented soybeans by Ph. linteus 03 (15.03 mg gallic acid equivalents/g and 63.24 mg rutin equivalents/g, respectively). The 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging activities of hot water extracts were higher than those of ethanolic extracts for fermented beans by three Ph. linteus strains. However, the superoxide anion radical scavenging ability of ethanolic extracts was higher than those of hot water extracts in the fermented beans of the three strains. The ferrous ion (Fe2+)-chelating abilities of hot water extracts were higher than those of ethanolic extracts in fermented beans by Ph. linteus 03 and 04. In contrast, ethanolic extracts were higher than hot water extracts in fermented beans by Ph. linteus 06. Overall, these results indicate that the fermentation by Ph. linteus strains increased the bioactive compounds and antioxidant activities of four beans.

Metabolomics: A useful tool for ischemic stroke research.

Ischemic stroke (IS) is a multifactorial and heterogeneous disease. Despite years of studies, effective strategies for the diagnosis, management and treatment of stroke are still lacking in clinical practice. Metabolomics is a growing field in systems biology. It is starting to show promise in the identification of biomarkers and in the use of pharmacometabolomics to help patients with certain disorders choose their course of treatment. The development of metabolomics has enabled further and more biological applications. Particularly, metabolomics is increasingly being used to diagnose diseases, discover new drug targets, elucidate mechanisms, and monitor therapeutic outcomes and its potential effect on precision medicine. In this review, we reviewed some recent advances in the study of metabolomics as well as how metabolomics might be used to identify novel biomarkers and understand the mechanisms of IS. Then, the use of metabolomics approaches to investigate the molecular processes and active ingredients of Chinese herbal formulations with anti-IS capabilities is summarized. We finally summarized recent developments in single cell metabolomics for exploring the metabolic profiles of single cells. Although the field is relatively young, the development of single cell metabolomics promises to provide a powerful tool for unraveling the pathogenesis of IS.

DHA alleviated hepatic and adipose inflammation with increased adipocyte browning in high-fat diet-induced obese mice.

Obesity is associated with accumulation of inflammatory immune cells in white adipose tissue, whereas thermogenic browning adipose tissue is inhibited. Dietary fatty acids are important nutritional components and several clinical and experimental studies have reported beneficial effects of docosahexaenoic acid (DHA) on obesity-related metabolic changes. In this study, we investigated effects of DHA on hepatic and adipose inflammation and adipocyte browning in high-fat diet-induced obese C57BL/6J mice, and in vitro 3T3-L1 preadipocyte differentiation. Since visceral white adipose tissue has a close link with metabolic abnormality, epididymal adipose tissue represents current target for evaluation. A course of 8-week DHA supplementation improved common phenotypes of obesity, including improvement of insulin resistance, inhibition of macrophage M1 polarization, and preservation of macrophage M2 polarization in hepatic and adipose tissues. Moreover, dysregulated adipokines and impaired thermogenic and browning molecules, considered obesogenic mechanisms, were improved by DHA, along with parallel alleviation of endoplasmic reticulum (ER) stress, mitochondrial dysfunction, and mitochondrial DNA stress-directed innate immunity. During 3T3-L1 preadipocytes differentiation, DHA treatment decreased lipid droplet accumulation and increased the levels of thermogenic, browning, and mitochondrial biogenesis molecules. Our study provides experimental evidence that DHA mitigates obesity-associated inflammation and induces browning of adipose tissue in visceral epididymal adipose tissue. Since obesity is associated with metabolic abnormalities across tissues, our findings indicate that DHA may have potential as part of a dietary intervention to combat obesity.

Endophytic Microbes from Medicinal Plants in Fenghuang Mountain as a Source of Antibiotics.

One of the largest concerns with world health today is still antibiotic resistance, which is making it imperative to find efficient alternatives as soon as possible. It has been demonstrated that microbes are reliable sources for the creation of therapeutic antibiotics. This research intends to investigate the endophytic microorganisms from several medicinal plants in Fenghuang Mountain (Jiangsu Province, China) and to discover new antibiotics from their secondary metabolites. A total of 269 endophytic strains were isolated from nine distinct medicinal plants. Taxonomic analysis revealed that there were 20 distinct species among these endophytes, with Streptomyces being the most common genus. Three of the target strains were chosen for scale-up fermentation after preliminary screening of antibacterial activities and the metabolomics investigation using LC-MS. These strains were Penicillium sp. NX-S-6, Streptomyces sp. YHLB-L-2 and Streptomyces sp. ZLBB-S-6. Twenty-three secondary metabolites (1-23), including a new sorbicillin analogue (1), were produced as a result of antibacterial activity-guided isolation. Through spectroscopic analysis using MS and NMR, the structures of yield compounds were clarified. According to antibacterial data, S. aureus or B. subtilis were inhibited to varying degrees by sorrentanone (3), emodic acid (8), GKK1032 B (10), linoleic acid (14), toyocamycin (17) and quinomycin A (21). The most effective antimicrobial agent against S. aureus, B. subtilis, E. coli and A. baumannii was quinomycin A (21). In addition, quinomycin A showed strong antifungal activity against Aspergillus fumigatus, Cryptococcus neoformans, and two clinical isolated strains Aspergillus fumigatus #176 and #339, with MIC as 16, 4, 16 and 16 µg/mL, respectively. This is the first time that bioprospecting of actinobacteria and their secondary metabolites from medicinal plants in Fenghuang Mountain was reported. The finding demonstrates the potential of endophytic microbes in medical plants to produce a variety of natural products. Endophytic microbes will be an important source for new antibiotics.

Construction of Liquid Crystal-Based Sensors Using Enzyme-Linked Dual-Functional Nucleic Acid on Magnetic Beads.

The development of liquid crystal (LC)-based sensors with superior performances such as high portability, excellent stability, great convenience, and remarkable sensitivity is highly demanded. This work proposes a new strategy for constructing the LC-based sensor using enzyme-linked dual-functional nucleic acid (d-FNA) on magnetic beads (MBs). The detection of kanamycin (KA) is demonstrated as a model. Acetylcholinesterase (AChE) is assembled onto the KA aptamer-modified MBs with a d-FNA strand that consists of an AChE aptamer and the complementary sequence of a KA aptamer. As the specific recognition of KA by its aptamer triggers the release of AChE from the MBs, the myristoylcholine (Myr) solution after incubation with the MBs causes the black image of the LCs due to the formation of the Myr monolayer at the aqueous/LC interface. Otherwise, in the absence of KA, AChE is still decorated on the MBs and causes the hydrolysis of Myr. Therefore, a bright image of LCs is obtained. The detection of KA is successfully achieved with a lower detection limit of 48.1 pg/mL. In addition, a thin polydimethylsiloxane (PDMS) layer-coated glass and a portable optical device are used to improve the stability and portability of the LC-based sensor to advance potential commercial applications. Furthermore, the detection of KA in milk with a portable device is demonstrated, showing the potential of the proposed enzyme-linked LC-based sensor.

Salvianolic acid B inhibits atherosclerosis and TNF-α-induced inflammation by regulating NF-κB/NLRP3 signaling pathway.

BACKGROUND: Inflammation is critical in the pathophysiology of atherosclerosis (AS). The aim of this study was to investigate the protective effect of salvianolic acid B (Sal B) on AS and to explore the molecular mechanism of tumor necrosis factor-α (TNF-α)-induced damage in human umbilical vein endothelial cells (HUVECs). METHODS: In vivo studies, LDLR-/- mice were fed a high-fat diet (HFD) for 14 weeks to establish an AS model to evaluate the protective effect of Sal B on the development of AS. Total cholesterol (TC), triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) levels were determined in the blood serum. En face and cross section lipid deposits were measured and quantified with Oil Red O staining. Hematoxylin and eosin (H&E) and Masson's trichrome staining were used to quantify atherosclerotic plaque size and collagen fiber content in aortic root sections. Reactive oxygen species (ROS) were detected in aortic root using dihydroethylenediamine (DHE) staining. Apoptosis rate was determined by TdT-mediated dUTP nick end labeling (TUNEL) staining. Immunofluorescence (IF) staining was used to detect the expression of the nuclear factor kappa-B (NF-κB) p65 and NOD-like receptor family pyrin domain containing 3 (NLRP3). To further investigate the protective effect of Sal B, we used TNF-α induced HUVECs inflammation model. We examined cell viability, lactate dehydrogenase (LDH) content, and ROS production. The transcription of NF-κB was evaluated by immunofluorescence. The mRNA levels of NLRP3, caspase-1, and IL-1ß were detected by RT-PCR. Pyroptosis related proteins were detected by Western blot. RESULTS: The change in the weight of the mice over time was an indication that Sal B had an effect on weight gain. IN VIVO STUDIES: we were able to show that the serum lipids TC, TG and LDL-C were increased in the model group and that the treatment with Sal B reduced the levels of serum lipids. Histological staining showed that the LDLR-/- mice had a large amount of foam cell deposition accompanied by inflammatory cell infiltration and the formation of atherosclerotic plaques in theMOD group. The pathological abnormalities were significantly improved by Sal B treatment. ROS release and apoptosis were significantly increased after HFD in aortic root, which was attenuated by Sal B. IF results showed that the expression of NF-κB p65 and NLRP3 was significantly increased in the MOD group and significantly decreased in the Sal B group, suggesting that Sal B may act through the NF-κB/NLRP3 pathway. And in vitro studies: inflammatory damage of HUEVCs was induced by TNF-α, and Sal B treatmented significantly increased cell viability and reduced LDH release. It was also found that Sal B inhibited ROS level increase after TNF-α-induced HUEVCs. Activation of NF-κB p65 by TNF-α stimulation, NF-κB p65 is transferred to the nucleus. Sal B treatment could reverse this effect. RT-PCR and Western blot showed that Sal B affected NF-κB transcription and NLRP3 inflammasome activation and could significantly inhibit TNF-α-induced NLRP3 inflammasome activation. These results suggest that Sal B may participate in antiatherosclerotic and inflammatory responses through the NF-κB/NLRP3 pathway. CONCLUSIONS: This study shows that Sal B ameliorates the development of AS lesions in HFD-induced LDLR-/- mice. Furthermore, under TNF-α conditions, Sal B reduced ROS release and reversed nuclear translocation of NF-κB, and inhibited atherosclerosis and inflammation by modulating the NF-κB/NLRP3 pathway.

A deep learning-based drug repurposing screening and validation for anti-SARS-CoV-2 compounds by targeting the cell entry mechanism.

The recent outbreak of Corona Virus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a severe threat to the global public health and economy, however, effective drugs to treat COVID-19 are still lacking. Here, we employ a deep learning-based drug repositioning strategy to systematically screen potential anti-SARS-CoV-2 drug candidates that target the cell entry mechanism of SARS-CoV-2 virus from 2635 FDA-approved drugs and 1062 active ingredients from Traditional Chinese Medicine herbs. In silico molecular docking analysis validates the interactions between the top compounds and host receptors or viral spike proteins. Using a SARS-CoV-2 pseudovirus system, we further identify several drug candidates including Fostamatinib, Linagliptin, Lysergol and Sophoridine that can effectively block the cell entry of SARS-CoV-2 variants into human lung cells even at a nanomolar scale. These efforts not only illuminate the feasibility of applying deep learning-based drug repositioning for antiviral agents by targeting a specified mechanism, but also provide a valuable resource of promising drug candidates or lead compounds to treat COVID-19.

Circulating miR-4739 and IGFBP-4 Levels in Postmenopausal Women with Osteoporosis and Osteoporotic Vertebral Fracture.

Objective: This study aimed to investigate the potential plasma miRNA-mRNA regulatory networks in postmenopausal women with osteoporosis (OP) and osteoporotic vertebral fracture (OVF). Methods: The study employed a cross-sectional design, and the microarray dataset GSE93883 was acquired from the Gene Expression Omnibus (GEO) to assess plasma miRNA profiles in postmenopausal women with osteoporosis (OP) and osteoporotic vertebral fracture (OVF). Subsequently, plasma microRNA-4739 (miR-4739) and Insulin-like Growth Factor Binding Protein-4 (IGFBP-4) levels were validated in a well-defined cohort comprising 210 postmenopausal women. This cohort consisted of three distinct groups: healthy controls (HC, n = 70), OP patients (n = 70), and OVF patients (n = 70). Results: Analysis of the GSE93883 dataset revealed a stepwise increase in four miRNAs (hsa-miR-4739, hsa-miR-4505, hsa-miR-4459, hsa-miR-665) in plasma samples from HC to OP patients to OVF patients. Conversely, plasma miR-4666a-3p showed a gradual decrease. We predicted six genes targeted by miR-4739 using six online databases. Plasma miR-4739 levels were significantly higher in OP and OVF patients compared to HC, especially in OVF patients. However, plasma IGFBP-4 exhibited an inverse pattern. Pearson analysis demonstrated a significant negative correlation between plasma miR-4739 and plasma IGFBP-4 in OP and OVF patients. Receiver operating characteristic (ROC) curve analysis of plasma miR-4739 yielded a sensitivity of 35.71% and specificity of 95.71% for predicting the presence of OP and a sensitivity of 71.43% and specificity of 95.71% for predicting OVF, with an AUC of 0.865. Moreover, the area under the curve (AUC) for IGFBP-4 was higher than that for plasma miR-4739 when differentiating OP patients from OVF patients. Conclusions: Circulating miR-4739 and IGFBP-4 demonstrated a negative correlation in OP and OVF patients, suggesting their potential as diagnostic biomarkers for OP and OVF in the future.

Network pharmacology and bioinformatics were used to construct a prognostic model and immunoassay of core target genes in the combination of quercetin and kaempferol in the treatment of colorectal cancer.

Purpose: CRC is a malignant tumor seriously threatening human health. Quercetin and kaempferol are representative components of traditional Chinese medicine (TCM). Previous studies have shown that both quercetin and kaempferol have antitumor pharmacological effects, nevertheless, the underlying mechanism of action remains unclear. To explore the synergy and mechanism of quercetin and kaempferol in colorectal cancer. Methods: In this study, network pharmacology, and bioinformatics are used to obtain the intersection of drug targets and disease genes. Training gene sets were acquired from the TCGA database, acquired prognostic-related genes by univariate Cox, multivariate Cox, and Lasso-Cox regression models, and validated in the GEO dataset. We also made predictions of the immune function of the samples and used molecular docking to map a model for binding two components to prognostic genes. Results: Through Lasso-Cox regression analysis, we obtained three models of drug target genes. This model predicts the combined role of quercetin and kaempferol in the treatment and prognosis of CRC. Prognostic genes are correlated with immune checkpoints and immune infiltration and play an adjuvant role in the immunotherapy of CRC. Conclusion: Core genes are regulated by quercetin and kaempferol to improve the patient's immune system and thus assist in the treatment of CRC.

Current Perspectives on Biological Therapy for COPD.

Chronic obstructive pulmonary disease (COPD) is a chronic, complex, and heterogeneous condition with significant mortality, morbidity, and socioeconomic burden. Given the heterogeneity, the current management of COPD, which mainly relies on bronchodilators and corticosteroids, cannot consider all COPD populations. Moreover, the present treatment modalities are directed at minimizing symptoms and reducing the risk of a future attack, but they exhibit few meaningful anti-inflammatory activities in preventing and reducing disease progression. Therefore, new anti-inflammatory molecules are needed to manage COPD better. Use of targeted biotherapy may obtain better results by increasing understanding of the underlying inflammatory process and identifying new biomarkers. In this review, we focus briefly on study of the underlying inflammatory process in the pathogenesis of COPD for better identification of novel target biomarkers, and we describe a novel class of anti-inflammatory biologics that are already under evaluation for their use in managing COPD.

Simultaneous removal of aflatoxin B1 and zearalenone in vegetable oils by hierarchical fungal mycelia@graphene oxide@Fe3O4 adsorbent.

Physical adsorbents for detoxification are widely used in vegetable oil industry. So far, the high-efficiency and low-cost adsorbents have not been well explored. Here, a hierarchical fungal mycelia@graphene oxide@Fe3O4 (FM@GO@Fe3O4) was fabricated as an efficient adsorbent for simultaneous removal of aflatoxin B1 (AFB1) and zearalenone (ZEN). The morphological, functional and structural characteristics of the prepared adsorbents were systematic investigated. Batch adsorption experiments in both single and binary systems were conducted, and the adsorption behaviours and mechanism were explored. The results indicated that the adsorption process occurred spontaneously and the mycotoxin adsorption could be described as physisorption through hydrogen bonding, π-π stacking, electrostatic and hydrophobic interactions. Due to good biological safety, magnetic manipulability, scalability, recyclability and easy regeneration, FM@GO@Fe3O4 performance is suitable for application as a detoxification adsorbent in vegetable oil industry. Our study addresses a novel green strategy for removing multiple mycotoxins by integrating the toxigenic isolates with advanced nanomaterials.

Psychological morbidity and chronic cough: which is predominant? A comparison of clinical characteristics.

Background: The clinical characteristics of chronic cough with pre-existing psychological co-morbidity (PCC) and chronic cough with secondary anxiety and depression (SCC) were compared to provide a basis for diagnosing and treating psychological co-morbidities in people with chronic cough. Methods: A prospective study was conducted to analyze the general clinical data between the PCC, SCC, and the chronic cough without anxiety and depression (CC) groups. A total of 203 patients with chronic cough were enrolled in the study. The final diagnosis was made in all cases using a combination of psychosomatic and respiratory diagnoses. The three groups' general clinical data, capsaicin cough sensitivity, cough symptom score, Leicester cough questionnaire (LCQ), and psychosomatic scale scores were compared among the three groups. The diagnostic value of the patient health questionnaire (PHQ)-9 and general anxiety disorder (GAD)-7 in patients with PCC and the follow-up information were analyzed. Results: Compared with the SCC group, the duration of cough in the PCC group was shorter (H = -3.54, p = 0.001), the night cough symptoms were milder (H = -4.60, p < 0.001), the total LCQ score was lower (H = -2.97, p = 0.009), and the PHQ-9 (H = 2.90, p = 0.011) and GAD-7 scores (H = 2.71, p = 0.002) were higher. When using PHQ-9 and GAD-7 scores for the combined prediction and diagnosis of PCC, the area under the curve (AUC) was 0.88, and the sensitivity and specificity were 90.0% and 73.85%, respectively. After 8 weeks of psychosomatic treatment, cough symptoms improved in the PCC group, but the psychological improvement was not significant. The psychological status of the SCC group improved after cough symptoms were ameliorated by etiologic or empirical treatment. Conclusion: The clinical characteristics of patients with PCC and SCC are different. The evaluation of psychosomatic scales is of value to distinguish between the two groups. Chronic cough patients with psychological co-morbidity benefit from the combined diagnosis of psychosomatic medicine in a timely fashion. PCC requires more attention in psychological therapy, but for SCC, targeting etiological treatment of the cough is preferred. Trial registration: The protocol was registered in the Chinese Clinical Trials Register (http://www.chictr.org.cn/) [ChiCTR2000037429].