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Atherosclerosis is an immune inflammatory disease and a major cause of mortality and morbidity worldwide. It is generally considered that a number of potent proinflammatory cytokines have a great influence on its pathogenesis, including IL-1β, IL-6, TNF-α, and NF-κB. A growing amount of empirical evidence indicates that the mechanism of cardiac dysfunction caused by lipopolysaccharide (LPS) is the activation of inflammation, but the exact mechanism in atherosclerosis is still unclear. Previous studies have shown that interferon-induced protein with tetratricopeptide repeats 1 (IFIT1) participates in inflammation, but the effects and possible mechanism of action of IFIT1 on proinflammatory response remain largely unexplained. We found that LPS induced upregulation of IFIT1 expression in a time- and concentration-dependent manner in human umbilical vein endothelial cells (HUVECs). Overexpression of IFIT1 significantly upregulated LPS-induced expression of IL-1β, IL-6, TNF-α, and NF-κB in HUVECs. IFIT1-siRNA treatment dramatically decreased LPS-induced expression of IL-1β, IL-6, TNF-α, and NF-κB in HUVECs. The above results show that LPS induces expression of IL-1β, IL-6, TNF-α, and NF-κB through upregulating IFIT1 expression in HUVECs, and suggested that IFIT1 could act as potential therapeutic target to ameliorate atherosclerosis-related diseases.

Background and aims Many clinical trials have demonstrated that statins convey protective effects against atherosclerosis independent of cholesterol-lowering capacities. Other evidence indicates that pyroptosis, a type of programmed cell death, is likely involved in atherosclerosis, but the effects and mechanisms of statins on pyroptosis must be further revealed. Methods Here, we explored the effects and mechanisms of atorvastatin on pyroptosis in human vascular endothelial cells by quantitative real-time polymerase chain reaction and Western blot analyses. Results Atorvastatin upregulated long non-coding RNA (lncRNA) NEXN-AS1 and the expression of NEXN at both the mRNA and protein levels in a concentration- and time-dependent manner. Atorvastatin inhibited pyroptosis by decreasing the expression levels of the canonical inflammasome pathway biomarkers NLRP3, caspase-1, GSDMD, IL-1β, and IL-18 at both the mRNA and protein levels. The promotion effects of atorvastatin on NEXN-AS1 and NEXN expression could be significantly abolished by knockdown of lncRNA NEXN-AS1 or NEXN, and its inhibitory effects on pyroptosis were also markedly offset by knock-down of lncRNA NEXN-AS1 or interference of NEXN. Conclusions These results demonstrated that atorvastatin regulated pyroptosis via the lncRNA NEXN-AS1-NEXN pathway, which provides a new insight into the mechanism of how atorvastatin promotes non-lipid-lower effects against the development of atherosclerosis and gives new directions on how to reverse atherosclerosis.

Epidemiologic studies focus on combined effects of multiple metals on bone mineral density (BMD) are scarce. Therefore, this study was conducted to examine associations of multiple metals exposure with BMD. Data of adults aged ≥20 years (n = 2545) from the US National Health and Nutrition Examination Survey (NHANES, 2011–2016) were collected and analyzed. Concentrations of metals were measured in blood (cadmium [Cd], lead [Pb], mercury [Hg], and manganese [Mn]) and serum (copper [Cu], selenium [Se], and zinc [Zn]) using inductively coupled plasma mass spectrometry and inductively coupled plasma dynamic reaction cell mass spectrometry, respectively. The weighted quantile sum (WQS) and Bayesian kernel machine regression (BKMR) models were performed to determine the joint effects of multiple metals exposure on lumbar and total BMD. The linear regression analyses showed Pb was negatively associated with BMDs. The WQS regression analyses revealed that the WQS index was inversely related to lumbar (β = −0.022, 95% CI: −0.036, −0.008) and total BMD (β = −0.015, 95% CI: −0.024, −0.006), and Se, Mn, and Pb were the main contributors for the combined effects. Additionally, nonlinear dose–response relationships between Pb, Mn, and Se and BMD, as well as a synergistic interaction of Pb and Mn, were found in the BKMR analyses. Our findings suggested co-exposure to Cd, Pb, Hg, Mn, Cu, Se, and Zn (above their 50th percentiles) was associated with reduced BMD, and Pb, Mn, and Se were the main contributors driving the overall effects.

Xiumei Hu,1,* Changmeng Wu,1,* Bo Situ,1,* Peifu Tian,2,* Taixue An,1 Qiang Li,1 Weilun Pan,1 Ruyi Zhang,1 Biao Yang,3 Dehua Sun,1 Yuhai Hu,2 Qian Wang,1,3 Lei Zheng1 1Department of Laboratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, People’s Republic of China; 2Department of Medicine Laboratory, Hankou Hospital of Wuhan, Wuhan 430010, People’s Republic of China; 3Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lei Zheng; Qian Wang Email nfyyzhenglei@smu.edu.cn; wangqian@smu.edu.cnObjective: The coronavirus disease (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is now rapidly spreading globally. Serological tests are an important method to assist in the diagnosis of COVID-19, used for epidemiological investigations. In this study, we aimed to investigate the impact of different types of vacuum collection tubes on the detection of SARS-CoV-2 IgM and IgG antibodies, using the colloidal gold immunochromatographic assay (GICA).Patients and Methods: A total of 112 patients with COVID-19 and 200 healthy control subjects with no infection were enrolled in this study. Their serum and plasma were collected into four different types of vacuum blood collection tubes. SARS-CoV-2 IgM and IgG specific antibodies in the plasma and serum were then detected by GICA and chemiluminescence assay (CA), respectively. In addition, the particle sizes of different colloidal gold solutions in the presence of different anticoagulants and coagulants were evaluated by both laser diffraction (Malvern) and confocal laser microscope, respectively.Results: Our results revealed that anticoagulated plasma with EDTA-K2 improved the positive detection rate of SARS-CoV-2 IgM antibodies. Furthermore, our results shown that the detection results by GICA and CA were highly consistent, especially, the results of EDTA-K2 anticoagulated plasma detected by GICA was more consistent with CA results. We confirmed that EDTA-K2 could improve the detection sensitivity of SARS-CoV-2 IgG antibodies by chelating excessive colloidal gold compared with sodium citrate or lithium heparin, these methodologies did not appear to cause false positives. Colloidal gold particles could be chelated and aggregated by EDTA-K2, but not by sodium citrate, lithium heparin and coagulants.Conclusion: GICA is widely used to detect antibodies for the advantages of convenient, fast, low cost, suitable for screening large sample and require minimal equipment. In this study, we found that EDTA-K2 amplified the positive antibody signal by chelating colloidal gold and improved the detection sensitivity of SARS-CoV-2 IgM and IgG antibodies when using the GICA. Therefore, we suggested that EDTA-K2 anticoagulated plasma was more suitable for the detection of SARS-CoV-2 antibodies.Keywords: EDTA-K2, SARS-CoV-2, antibodies, gold immunochromatographic assay; GICA

Atherosclerosis is a chronic vascular inflammatory disease that initially starts from an arterial intima lesion and endothelial barrier dysfunction. The purpose of this study was to investigate the role of TM4SF19, a recently identified member of the transmembrane 4L six superfamily, in vascular endothelial cell adherens junctions. We found TM4SF19 expression was significantly increased in atherosclerotic plaques and sera of patients with coronary heart disease (CHD) compared with healthy people by immunohistochemistry and ELISA. In vitro, human umbilical vein endothelial cells (HUVECs) were stimulated by lipopolysaccharides (LPS). TM4SF19 and VE-cadherin expression as well as cell adherens junctions were assessed. Additionally, LPS could upregulate TM4SF19 expression and downregulate VE-cadherin expression in HUVECs in a concentration dependent manner. Overexpression of TM4SF19 substantially aggravated LPS-induced reduction of VE-cadherin expression and attenuation of vascular endothelial cell adherens junctions. However, both the decreased VE-cadherin expression and weakened cell adherens junctions induced by LPS could be dramatically reversed when the expression of TM4SF19 was depressed. This study is the first to reveal the effect of TM4SF19 on endothelial cell adherens junctions. Meanwhile, our results also provide novel therapeutic strategies for atherosclerotic diseases.

Background and aims Long noncoding RNAs (lncRNAs) have recently been implicated in many biological and disease processes, but the exact mechanism of their involvement in atherosclerosis is unclear. The aberrant proliferation and migration of vascular smooth muscle cells (VSMCs) is a major contributor to the development of atherosclerotic lesions. This study aimed to investigate the potential effects of lncRNA ZNF800, a previously uncharacterized lncRNA, on VSMC proliferation and migration. Methods The expression of lncRNA ZNF800 in atherosclerotic plaque tissues was detected using reverse transcription–quantitative PCR (RT-qPCR), while the role and mechanism of lncRNA ZNF800 in proliferation and migration of VSMCs were investigated by CCK8 assay, transwell assay, scratch wound assay, RT-qPCR and Western blot. Results We found that lncRNA ZNF800 was significantly more abundant in atherosclerotic plaque tissues, and substantially suppressed the proliferation and migration of VSMCs. LncRNA ZNF800 had no effect on phosphatase and tensin homolog deleted on chromosome 10 (PTEN) mRNA expression but dramatically increased the levels of PTEN protein. Enhanced lncRNA ZNF800 expression inhibited the activity of the AKT/mTOR/HIF-1α signaling pathway, downregulated the expression of vascular endothelial growth factor α (VEGF-α) and matrix metalloproteinase 1 (MMP1), and suppressed VSMC proliferation and migration. These inhibitory effects of lncRNA ZNF800 were abolished by knockdown of PTEN. The inhibitory effects of lncRNA ZNF800 on cell proliferation and migration and the expression of VEGF-α and MMP1 were exacerbated by HIF-1α knockdown in VSMCs. Conclusions These findings demonstrated that lncRNA ZNF800 suppressed VSMC proliferation and migration by interacting with PTEN through a mechanism involving AKT/mTOR/HIF-1α signaling. Therefore, it may play a key atheroprotective role and represent a potential therapeutic target for atherosclerosis-related diseases.

Quercetin, a naturally occurring flavonoid, has been reported to exert antidepressant effects, however, the underlying mechanisms are still uncertain. Recent studies have demonstrated that Forkhead box transcription factor G1 (FoxG1) regulates the process of adult hippocampal neurogenesis (AHN) and exerts neuroprotective effects. In this study, we explored whether quercetin plays an anti-depressant role via regulation of FoxG1 signaling in mice and revealed the potential mechanisms. To explore the antidepressant effects of quercetin, mice were subjected to behavioral tests after a chronic unpredictable mild stress (CUMS) exposure. We found that chronic quercetin treatment (15 mg/kg, 30 mg/kg) obviously restored the weight loss of mice caused by CUMS and alleviated CUMS-induced depression-like behaviors, such as increased sucrose consumption, improved locomotor activity and shorten immobility time. In addition, to clarify the relationship between quercetin and AHN, we detected neurogenesis markers in the dentate gyrus (DG) of the hippocampus. Furthermore, FoxG1-siRNA was employed and then stimulated with quercetin to further investigate the mechanism by which FoxG1 participates in the antidepressant effects of quercetin. Our results indicate that chronic quercetin treatment dramatically increased the number of doublecortin (DCX)-positive and BrdU/NeuN-double positive cells. Besides, the expression levels of FoxG1, p-CREB and Brain-derived neurotrophic factor (BDNF) were also enhanced by quercetin in the DG. Strikingly, quercetin failed to reverse the levels of p-CREB and BDNF after FoxG1-siRNA was performed in SH-SY5Y cells and Neural Progenitor Cells (NPCs). Our results thus far suggest that quercetin might exert antidepressant effects via promotion of AHN by FoxG1/CREB/ BDNF signaling pathway.

Three new triterpenoid saponins, named julibroside J16 (2), julibroside J17 (3), and julibroside J21 (4), each of which possesses an oleanane triterpenoid aglycone of acacic acid, two monoterpenoid acids, and nine sugar moieties, together with one known saponin, julibroside II (1), were isolated from the stem bark of Albizia julibrissin by chromatographic methods. Their structures were established by chemical and spectroscopic means. Saponins 1, 2, and 4 showed inhibitory activities against Bel 7402 human cancer cell line in vitro.

Two new saponins have been isolated from the stem barks of Albizzia julibrissin Durazz, and their structures identified as 3-O-[beta-D-xylopyranosyl-(1 --2)-beta-D-fucopyranosyl-(1 --6)-beta-D-2-deoxy-2-acetoamidoglucopyranosyl]-21-O-{(6S)-2-trans-2-hydroxymethyl-6-methyl-6-O-[4-O-((6S)-2-trans-2-hydroxymethyl-6-hydroxy-6-methyl-2,7-octadienoyl)-beta-D-quinovopyranosyl]-2,7-octadienoyl}-acacic acid-28-O-beta-D-glucopyranosyl-(1 --3)-[alpha-L-arabinofuranosyl-(1 --4)]-alpha-L-rhamnopyranosyl-(1 --2)-beta-D-glucopyranosyl ester (1) and 3-O-[beta-D-xylopyranosyl-(1 --2)-beta-D-fucopyranosyl-(1 --6)-beta-D-2-deoxy-2-acetoamidoglucopyranosyl]-21-O-{(6S)-2-trans-2-hydroxymethyl-6-methyl-6-O-[3-O-((6S)-2-trans-2-hydroxymethyl-6-hydroxy-6-methyl-2,7-octadienoyl)-beta-D-quinovopyranosyl]-2,7-octadienoyl}acacic acid 28-O-beta-D-glucopyranosyl-(1 --3)-[alpha-L-arabinofuranosyl-(1 --4)]-alpha-L-rhamnopyranosyl-(1 --2)-beta-D-glucopyranosyl ester (2), based on chemical and spectral evidences, named as julibroside J19 and julibroside J18, respectively. Both compounds show significant inhibition action against HeLa, Bel-7402 and MDA-MB-435 cancer cell lines in vitro.

The structures of four new diastereoisomeric triterpenoidal saponins Julibroside J5, J8, J12 and J13 (1-4) isolated from Albizia julibrissin Durazz. (Leguminosae) have been determined on the basis of comprehensive spectroscopic analysis and chemical degradation. Julibroside, J8 and J13 showed marked cytotoxic activities against Bel-7402 cancer cell line at 100 microg/mL.

A triterpenoid saponin (1) was obtained from the stem barks of Albizia julibrissin Durazz. Its structure was elucidated as 3-O-[beta-D-xylopyranosyl-(1 --2)-alpha-L-arabinopyranosyl-(1 --6)-beta-D-glucopyranosyl]-21-O-[(6S)-2-trans-2-hydroxymethyl-6-methyl-6-O-beta-D-quinovopyranosyl-2, 7-octadienoyl]-16-deoxy-acacic acid 28-O-beta-D-glucopyranosyl-(1 --3)-[alpha-L-arabinofuranosyl-(1 --4)]-alpha-L-rhamnopyranosyl-(1 --2)-beta-D-glucopyranosyl ester (1), named as Julibroside J26, based on the chemical and spectral methods.

A new isomer of Julibroside J2 (Chen, S.P., Zhang, R.Y., Ma, L.B. and Tu, G.Z. Acta Pharm. Sinica, 1997, 32, 110–115) was obtained from the cytotoxic fraction of 95% ethanol extracts of stem barks of Albizia julibrissin Durazz, together with Julibroside J2. Its structure was elucidated as 3-O-[β-D-xylopyranosyl-(1 → 2)-α-L-arabinopyranosyl-(1 → 6)-β-D-glucopyranosyl]-21-O-{(6S)-2-trans-2-hydroxymethyl-6-methyl-6-O-[3-O-((6S)-2-trans-2-hydroxymethyl-6-methyl-6-hydroxy-2,7 -octadienoyl)-β-D-quinovopyranosyl]-2,7-octadienoyl} acacic acid 28-O-β-D-glucopyranosyl-(1 → 3)-[α-L-arabinofuranosyl-(1 → 4)]-α-L-rhamnopyranosyl-(1 → 2)-β-D-glucopyranosyl ester(1), named as Julibroside J7, based on chemical and spectral methods. Julibroside J2 showed good inhibitory action against KB cell line in vitro.

A novel flavonol glycoside named wanepimedoside A was isolated from the whole plant of Epimedium wanshanense, along with fifteen known flavonoids, anhydroicaritin, desmethylanhydroicaritin, icarisid I and II, quercetin, ikarisoside A and B, sagittatoside B, 2"-O-rhamnosylicarisid II, icariin, 2"-O-rhamnosylikarisoside A, epimedin B, epimedin C, and diphylloside A and B.

An anhydroicaritin 3-O-rhamnosylrhamnoside from Epimedium koreanum is defined as the 3-O-alpha-L-[alpha-L-rhamnopyranosyl(1-->2)rhamnopyranoside] on the basis of 2D NMR evidence. Complete assignments of the 1H and 13C NMR spectra of this compound are presented for the first time. The NMR distinction of 1-->2, 1-->3 and 1-->4 linked rhamnopyranosylrhamnopyranosides are discussed and indicate that baohuosides III and V from E. davidii and baohuoside VI from E. davidii and E. pubescens, respectively, are (1-->2) linked.

Julibroside J1 is a new triterpenoid saponin which contains one triterpene, two monoterpenes and nine sugar residues. The structure has been determined almost exclusively by high-resolution NMR methods. The 1H and 13C NMR spectra of Julibroside J1 C5D5N have been assigned by homonuclear and heteronuclear correlation experiments, such as COSY, CH-COSY, TOCSY, HMBC, HMQC-COSY, HMQC-TOCSY and NOESY. Anomeric configurations were obtained by combined use of 1JCH and 3JH1,H2 and NOESY data. The particular sugar residues were identified by utilizing 3JHH values obtained from TOCSY cross-peaks, NOE difference spectra, and several 1D-TOCSY spectra, and three-bond intra-ring cross-peaks from a HMBC spectrum. Linkage assignments were made using the HMBC spectrum, and supplemented by NOE data from the NOESY spectrum. The structure of Julibroside J1 was characterized as 3-O-[β- d - xylopyranosyl -(1 → 2)-α- l - arabinopyranosyl -(1 → 6)-β- d - glucopyranosyl ]-21-O-{(6S)-2- trans-2-hydroxymethyl -6- methyl -6-O-[4-O-((6S)-2-trans-2,6- dimethyl -6-O-(6- deoxy -β- d - glucopyranosy )-2,7- octadienoyl )-6- deoxy -β- d - glycopyranosyl ]-2,7- octadienoyl }- acacic acid 28-O-{β- d - glucopyranosyl -(1 → 3)-[α- l - arabinofuranosyl -(1 → 4)]-α- l - rhamnopyranosyl -(1 → 2)}-β- d - glucopyranosyl ester.

Glyasperin E 1, a new 3-phenoxychromen-4-one derivative, has been isolated from the roots of Glycyrrhiza aspera. The structure of glyasperin E 1 was established first on the basis of spectroscopic evidence and then confirmed by synthesis. Glyasperin E dimethyl ether 1a was synthesized by way of the ring closure of compound 5b with ethoxalyl chloride in pyridine, and then decarboxylation, methylation and prenylation.

Two new pentacyclic triterpenoid sapogenins of the 18alpha H-oleana-9(11),12-diene type named glyyunnansapogenins G and H were isolated from the roots of GLYCYRRHIZA YUNNANENSIS Cheng f. et L. K. Tai. Their structures were elucidated as 18alpha H-oleana-9(11),12-diene-3beta,21alpha,29-triol and 18alpha H-3beta,21alpha-dihydroxyoleana-9(11),12-dien-29-oic acid, respectively, by spectroscopic methods. This is the first report of the occurrence of the 18alpha H series of oleana-9(11),12-diene compounds in nature.

A rapid high-performance liquid chromatographic method for the simultaneous separation and determination of five flavonoids and four coumarins, viz., liquiritin, isoliquiritin, liquiritigenin, isoliquiritigenin, glycycoumarin, isoglycycoumarin, licochalcone A, glycyrol and isoglycyrol, in licorice root is described. The separation system consists of a reversed-phase column and a gradient elution system containing acetonitrile and 3% acetic acid in water. The compounds were detected at 310 and 365 nm successively. The recoveries of the flavonoids and coumarins were 95.6–105.2% with relative standard deviations of 0.62–4.24%. The contents of the above nine compounds in three species of licorice root produced in China were determined.

Two new oleanane triterpenoids, named glyyunnansapogenins C and E, together with the known compound macedonic acid, were isolated from roots of Glycyrrhiza yunnanensis. The structures of glyyunnansapogenins C and E were established as 3β-hydroxy-16-oxo-oleana-11,13(18)-dien-30-oic acid and 3β,21α,24-trihydroxy-oleana-11,13(18)-dien-29-oic acid, respectively, by spectroscopic methods and chemical transformations.

A new triterpenoidal saponin (1: Julibroside J(21)) with a xylopyranosyl moiety located at its C-21 side chain was isolated from Albizia julibrissin DURAZZ. (Leguminosae), and its structure was determined on the basis of comprehensive spectroscopic analyses. Compound 1 showed marked inhibitory action against Bel-7402 cancer cell line at 10 microg/ml.

Four triterpenoidal saponins, prosaikogenin A and saikosaponins b1, n and o, were isolated from the roots of the title plant for the first time. Saikosaponin O is a new compound, which was identified as 3β,16β,23,28- tetrahydroxyolean-11,13(18)-diene -3-O-β- d -glucopyranosyl-(1 → 2)-β- d -glucopyranosyl-(1 → 6)-[β- d - glucopyranosyl-(1 → 2)]-β- d -glucopyranoside .

A new 9,10-dihydrophenanthrene derivative named epimedoicarisoside A was isolated from the aerial parts of Epimedium koreanum along with ten known flavonoids. The structure of this compound was determined on the basis of spectral analysis (FAB-Mass spectrometry, 1 H 1 H COSY, 13 C COSY, DEPT, and 13 C long range COSY, etc.) as 2-hydroxy-3,4,6,7-tetramethoxy-9,10-dihydrophenanthrene-2-O-β- d -glucopyranoside. The known compounds were identified as icariin, epimedoside C, icarisid I, baohuoside I, diphylloside A, baohuoside II, 2″-O-rhamnosylicarisid II, sagittatoside A, hyperoside and icaritin-3-O-rhamnopyranoside.

A novel flavonol glycoside named caohuoside-B was isolated from the aerial parts of Epimedium koreanum , along with a known flavonol glycoside, epimedokoreanoside-I. Their structures were established by spectroscopic methods. The new compound was elucidated as anhydroicaritin 3-O-β- d -(4,6-O- diacetyl ) glucopyranosyl -(1 → 3)α- l -(4″-O- acetylrhamnopyranoside )-7-O-β- d -glucopyranoside .

A new difuranoflavone, epimedokoreanin A, was isolated from the aerial parts of Epimedium koreanum, in addition to four known flavonol glycosides, sagittatoside B, ikarisoside F, epimedin B and epimedin C.

Glyasperin E 1, a new 3-phenoxychromen-4-one derivative, has been isolated from the roots of Glycyrrhiza aspera. The structure of glyasperin E 1 was established first on the basis of spectroscopic evidence and then confirmed by synthesis. Glyasperin E dimethyl ether 1a was synthesized by way of the ring closure of compound 5b with ethoxalyl chloride in pyridine, and then decarboxylation, methylation and prenylation.

Four new isoprenoid-substituted dibenzoylmethane derivatives, glyinflanins A (1), B (2), C (3), and D (4) were isolated from the roots of Glycyrrhiza infalta. The structures of glyinflanins A-D were elucidated by spectroscopic and chemical methods

Four new prenylated flavonoids, glyasperins A (1), B (2), C (3),n and D (4), along with ten known compounds were isolated from the roots of Glycyrrhiza aspera. The structures of glyasperins A-D were elucidated by spectroscopic methods

Five new isoprenoid-substituted flavonoids, glyasperins F (1), G (2), H (3), I (4) and J (5) were isolated from the roots of Glycyrrhiza aspera. The structures of glyasperins F-J were elucidated by spectroscopic methods