A Novel Zn(II) Coordination Polymer: Fluorescence Performances, Molecular Docking and Loaded with Bleomycin-Hydrogels on Hemangiomas.

In this study, we successfully synthesized an innovative 1D-Zn(II) coordination polymer, denoted as [Zn(L)(H2O)2]n, employing the Schiff base {4-[(2-hydroxy-3-methoxy-benzylidene)-amino]-benzoic acid} (H2L). The Schiff base was obtained through the reaction of 4-aminobenzoic acid and o-vanillin under slow volatilization conditions. The resulting compound exhibits remarkable green fluorescence emission properties, indicating its potential as a novel fluorescent and sensing material. Hydrogels based on hyaluronic acid (HA) and carboxymethyl chitosan (CMCS), denoted as HA/CMCS hydrogels, were synthesized using a chemical method. Additionally, we utilized bleomycin as a model drug to synthesize a novel bleomycin metal gel and assessed its anti-hemangioma activity. Molecular docking simulations revealed that the Zn complex can form stable bonds with the key target, involving the methoxy and carboxyl groups on the Zn complex.

Essential oil from Fructus Alpiniae zerumbet ameliorates vascular endothelial cell senescence in diabetes by regulating PPAR-γ signalling: A 4D label-free quantitative proteomics and network pharmacology study.

ETHNOPHARMACOLOGICAL RELEVANCE: Vascular endothelial cell senescence is associated with cardiovascular complications in diabetes. Essential oil from Fructus Alpiniae zerumbet (Pers.) B.L.Burtt & R.M.Sm. (EOFAZ) has potentially beneficial and promising diabetes-related vascular endothelial cell senescence-mitigating effects; however, the underlying molecular mechanisms remain unclear. AIM OF THE STUDY: To investigate the molecular effects of EOFAZ on vascular endothelial cell senescence in diabetes. MATERIALS AND METHODS: A diabetes mouse model was developed using a high-fat and high-glucose diet (HFD) combined with intraperitoneal injection of low-dose streptozotocin (STZ, 30 mg/kg) and oral treatment with EOFAZ. 4D label-free quantitative proteomics, network pharmacology, and molecular docking techniques were employed to explore the molecular mechanisms via which EOFAZ alleviates diabetes-related vascular endothelial cell senescence. A human aortic endothelial cells (HAECs) senescence model was developed using high palmitic acid and high glucose (PA/HG) concentrations in vitro. Western blotting, immunofluorescence, SA-ß-galactosidase staining, cell cycle, reactive oxygen species (ROS), cell migration, and enzyme linked immunosorbent assays were performed to determine the protective role of EOFAZ against vascular endothelial cell senescence in diabetes. Moreover, the PPAR-γ agonist rosiglitazone, inhibitor GW9662, and siRNA were used to verify the underlying mechanism by which EOFAZ combats vascular endothelial cell senescence in diabetes. RESULTS: EOFAZ treatment ameliorated abnormal lipid metabolism, vascular histopathological damage, and vascular endothelial aging in diabetic mice. Proteomics and network pharmacology analysis revealed that the differentially expressed proteins (DEPs) and drug-disease targets were associated with the peroxisome proliferator-activated receptor gamma (PPAR-γ) signalling pathway, a key player in vascular endothelial cell senescence. Molecular docking indicated that the small-molecule compounds in EOFAZ had a high affinity for the PPAR-γ protein. Western blotting and immunofluorescence analyses confirmed the significance of DEPs and the involvement of the PPAR-γ signalling pathway. In vitro, EOFAZ and rosiglitazone treatment reversed the effects of PA/HG on the number of senescent endothelial cells, expression of senescence-related proteins, the proportion of cells in the G0/G1 phase, ROS levels, cell migration rate, and expression of pro-inflammatory factors. The protective effects of EOFAZ against vascular endothelial cell senescence in diabetes were aborted following treatment with GW9662 or PPAR-γ siRNA. CONCLUSIONS: EOFAZ ameliorates vascular endothelial cell senescence in diabetes by activating PPAR-γ signalling. The results of the present study highlight the potential beneficial and promising therapeutic effects of EOFAZ and provide a basis for its clinical application in diabetes-related vascular endothelial cell senescence.

Essential oil from Fructus Alpinia zerumbet ameliorates atherosclerosis by activating PPARγ-LXRα-ABCA1/G1 signaling pathway.

BACKGROUND: Atherosclerosis (AS) is a progressive chronic disease. Currently, cardiovascular diseases (CVDs) caused by AS is responsible for the global increased mortality. Yanshanjiang as miao herb in Guizhou of China is the dried and ripe fruit of Fructus Alpinia zerumbet. Accumulated evidences have confirmed that Yanshanjiang could ameliorate CVDs, including AS. Nevertheless, its effect and mechanism on AS are still largely unknown. PURPOSE: To investigate the role of essential oil from Fructus Alpinia zerumbet (EOFAZ) on AS, and the potential mechanism. METHODS: A high-fat diet (HFD) ApoE-/- mice model of AS and a oxLDL-induced model of macrophage-derived foam cells (MFCs) were reproduced to investigate the pharmacological properties of EOFAZ on AS in vivo and foam cell formation in vitro, respectively. The underlying mechanisms of EOFAZ were investigated using Network pharmacology and molecular docking. EOFAZ effect on PPARγ protein stability was measured using a cellular thermal shift assay (CETSA). Pharmacological agonists and inhibitors and gene interventions were employed for clarifying EOFAZ's potential mechanism. RESULTS: EOFAZ attenuated AS progression in HFD ApoE-/- mice. This attenuation was manifested by the reduced aortic intima plaque development, increased collagen content in aortic plaques, notable improvement in lipid profiles, and decreased levels of inflammatory factors. Moreover, EOFAZ inhibited the formation of MFCs by enhancing cholesterol efflux through activiting the PPARγ-LXRα-ABCA1/G1 pathway. Interestingly, the pharmacological knockdown of PPARγ impaired the beneficial effects of EOFAZ on MFCs. Additionally, our results indicated that EOFAZ reduced the ubiquitination degradation of PPARγ, and the chemical composition of EOFAZ directly bound to the PPARγ protein, thereby increasing its stability. Finally, PPARγ knockdown mitigated the protective effects of EOFAZ on AS in HFD ApoE-/- mice. CONCLUSION: These findings represent the first confirmation of EOFAZ's in vivo anti-atherosclerotic effects in ApoE-/- mice. Mechanistically, its chemical constituents can directly bind to PPARγ protein, enhancing its stability, while reducing PPARγ ubiquitination degradation, thereby inhibiting foam cell formation via activation of the PPARγ-LXRα-ABCA1/G1 pathway. Simultaneously, EOFAZ could ameliorates blood lipid metabolism and inflammatory microenvironment, thus synergistically exerting its anti-atherosclerotic effects.

Time-restricted feeding affects the fecal microbiome metabolome and its diurnal oscillations in lung cancer mice.

The homeostasis of the gut microbiota and circadian rhythm is critical to host health, and both are inextricably intertwined with lung cancer. Although time-restricted feeding (TRF) can maintain circadian synchronization and improve metabolic disorders, the effects of TRF on the fecal microbiome, metabolome and their diurnal oscillations in lung cancer have not been discussed. We performed 16S rRNA sequencing and untargeted metabonomic sequencing of the feces prepared from models of tumor-bearing BALB/c nude mice and urethane-induced lung cancer. We demonstrated for the first time that TRF significantly delayed the growth of lung tumors. Moreover, TRF altered the abundances of the fecal microbiome, metabolome and circadian clocks, as well as their rhythmicity, in lung cancer models of tumor-bearing BALB/c nude mice and/or urethane-induced lung cancer C57BL/6J mice. The results of fecal microbiota transplantation proved that the antitumor effects of TRF occur by regulating the fecal microbiota. Notably, Lactobacillus and Bacillus were increased upon TRF and were correlated with most differential metabolites. Pathway enrichment analysis of metabolites revealed that TRF mainly affected immune and inflammatory processes, which might further explain how TRF exerted its anticancer benefits. These findings underscore the possibility that the fecal microbiome/metabolome regulates lung cancer following a TRF paradigm.

Mechanism of the HIF-1α/VEGF/VEGFR-2 pathway in the proliferation and apoptosis of human haemangioma endothelial cells.

Haemangiomas (HAs) are prevalent vascular endothelial cell tumours. With respect to the possible involvement of HIF-1α in HAs, we have explored its role in haemangioma endothelial cell (HemEC) proliferation and apoptosis. shRNA HIF-1α and pcDNA3.1 HIF-α were manipulated into HemECs. HIF-α, VEGF, and VEGFR-2 mRNA and protein levels were assessed by qRT-PCR and Western blotting. Cell proliferation and viability, cell cycle and apoptosis, migration and invasion, and ability to form tubular structures were assessed by colony formation assay, CCK-8, flow cytometry, Transwell assay, and tube formation assay. Cell cycle-related protein levels, and VEGF and VEGFR-2 protein interaction were detected by Western blot and immunoprecipitation assays. An Haemangioma nude mouse model was established by subcutaneous injection of HemECs. Ki67 expression was determined by immunohistochemical staining. HIF-1α silencing suppressed HemEC neoplastic behaviour and promoted apoptosis. HIF-1α facilitated VEGF/VEGFR-2 expression and the VEGF had interacted with VEGFR-2 at protein - protein level. HIF-1α silencing arrested HemECs at G0/G1 phase, diminished Cyclin D1 protein level, and elevated p53 protein level. VEGF overexpression partially abrogated the effects of HIF-1α knockdown on inhibiting HemEC malignant behaviours. Inhibiting HIF-1α in nude mice with HAs repressed tumour growth and Ki67-positive cells. Briefly, HIF-1α regulated HemEC cell cycle through VEGF/VEGFR-2, thus promoting cell proliferation and inhibiting apoptosis.

1,8-Cineole ameliorates diabetic retinopathy by inhibiting retinal pigment epithelium ferroptosis via PPAR-γ/TXNIP pathways.

1,8-Cineole, the main component of volatile oil in aromatic plants, has diverse pharmacological properties, including antioxidant, anti-inflammatory, and anti-cancer properties. Diabetic retinopathy (DR) is a common microvascular complication of diabetes mellitus (DM). Here, we investigated the protective effect of 1,8-cineole on DR and found that 1,8-cineole treatment could alter the expression of several genes in both high glucose (HG)-induced ARPE-19 cells and retinal tissues of DM mice, as well as inhibit ferroptosis. Subsequent investigations into the molecular mechanisms underlying this inhibition revealed that expression of thioredoxin-interacting protein (TXNIP) was significantly upregulated while that of peroxisome proliferator-activated receptor γ (PPAR-γ) was significantly downregulated in HG-induced ARPE-19 cells, and treatment with 1,8-cineole could effectively reverse these changes. Treatment with a PPAR-γ pharmacological agonist (rosiglitazone), alone or combined with 1,8-cineole, significantly inhibited the transcription of TXNIP and ferroptosis in HG-induced ARPE-19 cells. Conversely, pretreatment with GW9662, a PPAR-γ inhibitor, upregulated the transcription and expression of TXNIP in HG-induced ARPE-19 cells; 1,8-cineole failed to reverse this upregulated expression. To explore these relationships, we constructed a PPAR-γ adenovirus shRNA to elucidate the effect of 1,8-cineole on the negative regulation of TXNIP by PPAR-γ. Taken together, the present findings indicate that HG-induced ferroptosis in retinal tissue plays an essential role in the pathogenesis of DR, which can be ameliorated by 1,8-cineole.

Dietary Effects on Chronic Venous Disease.

BACKGROUND: Diet is fundamental to maintaining and improving human health. There is ample evidence identifying the beneficial and/or harmful effects of diet on noncommunicable diseases such as obesity, diabetes mellitus, and cardiovascular disease. However, the associations of the diet to chronic venous disease has not been fully described. METHODS: Data were collected through a cross-sectional survey conducted on 1,571 community-dwelling adults in 2018. Diet intake frequency was assessed using valid food group consumption frequency questionnaires. Multivariable logistic regression models were used to evaluate the association of diet with chronic venous disease. RESULTS: In total, 857 participants were diagnosed with chronic venous disease. Those who ate soybean products daily and 4-6 days/week had a 51-31% lower risk of chronic venous disease compared with those who only occasionally consumed soybean food, respectively. Participants who consumed eggs and egg products 1-3 days/week versus those who only occasionally ate eggs showed a lower risk of chronic venous disease [odds ratio (OR) 0.542, 95% confidence interval (CI) 0.375-0.782]. Eating fried food 4-6 days each week was associated with an increased risk of chronic venous disease (OR 3.872, 95% CI 1.263-11.599) compared with those who only occasionally ate fried foods. There is a decreasing tendency of the adjusted OR for eating soybean products daily with the severity of disease [chronic venous disease (C0-C2): OR 0.575, 95% CI 0.408-0.812; chronic venous insufficiency (C3-C6): OR 0.222, 95% CI 0.114-0.435]. CONCLUSIONS: A higher frequency in the consumption of soybean products and eggs were associated with a lower risk of chronic venous disease. High level of fried food consumption was positively associated with risk of chronic venous disease. There are certain specific trends in relation to dietary consumption and severity of disease, although these trends were less strong. These associations are largely independent of other dietary and nondietary factors.

A Small Ligand That Selectively Binds to the G-quadruplex at the Human Vascular Endothelial Growth Factor Internal Ribosomal Entry Site and Represses the Translation.

G-quadruplexes are believed to have important biological functions, so many small molecules have been screened or developed for targeting G-quadruplexes. However, it is still a major challenge to find molecules that recognize specific G-quadruplexes. Here, by using a combination of surface plasmon resonance, electrospray ionization mass spectrometry, circular dichroism, Western blot, luciferase assay, and reverse transcriptase stop assay, we observed a small molecule, namely, oxymatrine (OMT) that could selectively bind to the RNA G-quadruplex in 5'-untranslated regions (UTRs) of human vascular endothelial growth factor (hVEGF), but could not bind to other G-quadruplexes. OMT could selectively repress the translation of VEGF in cervical cancer cells. Furthermore, it could recognize VEGF RNA G-quadruplexes in special conformations. The results indicate that OMT may serve as a potentially special tool for studying the VEGF RNA G-quadruplex in cells and as a valuable scaffold for the design of ligands that recognize different G-quadruplexes.

Clinical outcomes of venous self-expanding stent placement for iliofemoral venous outflow obstruction.

OBJECTIVE: In the present study, we evaluated the feasibility of a self-expanding venous stent for treating iliofemoral venous obstruction. METHODS: The present retrospective study reviewed the data from 49 patients who had undergone Zilver Vena (Cook Medical, Bloomington, Ind) stent placement for treatment of iliofemoral venous obstruction from September 2017 to March 2019. All patients had undergone received follow-up duplex ultrasound examinations to assess for stent patency. The Villalta scores and Venous Clinical Severity Scores (VCSSs) were also calculated to stratify the postoperative improvement in disease. RESULTS: Of the 49 patients, 19 had had acute deep vein thrombosis, 7, nonthrombotic iliac venous lesions, and 23, post-thrombotic syndrome. At 1 year after Zilver Vena stent placement, the primary, assisted primary, and secondary patency rates were 93.8%, 95.9%, and 97.9%, respectively. The baseline median Villalta score before treatment for those with post-thrombotic syndrome was 19 (range, 11-30), and the median VCSS for the patients with post-thrombotic syndrome and nonthrombotic iliac venous lesions was 11 (range, 6-25). At 1 year after stent placement, the median Villalta score for the post-thrombotic syndrome patients was 4.0 (range, 2-18), and the median VCSS for the post-thrombotic syndrome and nonthrombotic iliac venous lesions patients was 3.0 (range, 2-12). CONCLUSIONS: Venous placement of self-expanding stents offers excellent 1-year patency rates and improved the outcomes of patients with iliofemoral venous obstruction caused by acute deep vein thrombosis, nonthrombotic iliac venous lesions, and post-thrombotic syndrome.

Association of High Serum Homocysteine Levels and Severe Chronic Venous Disease.

BACKGROUND: Homocysteine (Hcy) is considered as a modifiable risk factor for vascular disease. This study was aimed to explore the association between serum concentration and the severity of primary chronic venous disease (CVD). METHODS: Clinical data of 582 patients diagnosed with primary CVD were collected and analyzed retrospectively. The Clinical Etiology Anatomy Pathophysiology classification system was used to grade the severity of chronic venous disease. Patients were divided into 2 groups (group A: C1-C3; group B: C4-C6). The association between serum homocysteine levels and the severity of primary chronic venous disease was investigated using rank sum test and logistic regression. RESULTS: The difference between the level of homocysteine in each grade has statistical significance. Group A has higher median Hcy concentrations than Group B (15.40 µmol/L vs. 14.05 µmol/L, P< 0.01). Further binary logistic regression showed no statistical significance among the level of Hcy (11.00-14.75 µmol/L [OR 0.66, 95% CI 0.40-1.11, P= 0.12], 14.75-20.38µmol/L [OR 0.97, 95% CI 0.59-1.69, P = 0.89], ≥20.38 µmol/L [OR 0.67, 95% CI 0.41-1.10, P = 0.11]), but age (OR 1.03, 95% CI 1.01-1.04, P< 0.01) and female (OR 0.41, 95% CI 0.28-0.59, P< 0.01) are associated with more severe stages of CVD. CONCLUSIONS: Higher level of Hcy is associated with more severe stages of CVD, but it not an independent risk factor. However, Advanced age and female are risk factors for CVD development based on logistic regression analysis.

Predictive Model for Pulmonary Embolism in Patients with Deep Vein Thrombosis.

BACKGROUND: To develop and verify a risk predictive model/scoring system for pulmonary embolism (PE) among hospitalized patients with deep venous thrombosis of the lower extremities (LDVT). METHODS: 776 patients with LDVT were enrolled in a case-control study between January 2016 and June 2017 from the Vascular Surgery Department of Shanxi Dayi Hospital, China. They were randomly divided into development (543 patients, 70%) and validation (233 patients, 30%) databases. Based on the results of pulmonary computed tomography arteriography, patients were divided into 2 categories; those with PE were designated as the case group, whereas those without comprised the controls. A logistic regression model and scoring system for PE in patients with LDVT was established in the development database and verified in the validation database. Scoring system (Shanxi Dayi Hospital score [SDH score]) was tabulated as follows: right lower extremity or bilateral lower extremities, 1; surgery or immobilization, 1; malignant tumor, 1; history of venous thromboembolism (VTE), 2; D-dimer >1,000 ng/mL, 2; and unprovoked, 2. Calibration and discrimination of the model were assessed by the Hosmer-Lemeshow goodness of fit test and the area under the receiver operating characteristic curve (AUC). Wells score, the Revised Geneva score, and the SDH score for predictive value of PE by AUC in the validation database were compared. RESULTS: 776 patients with LDVT were divided into 2 risk categories based on the scores from the risk model as follows: PE unlikely (score <3) and PE likely (score ≥3). Sensitivity, specificity, and crude agreement of the SDH score in the development database were 76.39%, 55.89%, and 61.33%, respectively. In the validation database, the logistic regression model showed good calibration and discriminative power. The Hosmer-Lemeshow goodness of fit test P value was >0.05, and the AUC was 0.705 (95% CI: 0.634-0.776, P < 0.001). The SDH score also showed good discriminative power, and the AUC was 0.702 (95% CI: 0.631-0.774, P < 0.001). Sensitivity, specificity, and crude agreement of the SDH score in the validation database were 67.61%, 61.73%, and 63.52%, respectively. AUC for the Wells score and the Revised Geneva score was 0.611 (95% CI: 0.533-0.688, P = 0.007) and 0.585 (95% CI: 0.503-0.666, P = 0.040), respectively. Difference of the AUC was not statistically significant between the Wells score and the SDH score (0.611 vs. 0.702, P = 0.059) but was so between the Revised Geneva score and the SDH score (0.585 vs. 0.702, P = 0.016). Sensitivity of the Wells score, Revised Geneva score, and the SDH score (64.79%, 67.61% vs. 67.61%) was not statistically significant. However, the specificity of the Wells score and Revised Geneva score was significantly lower than that of the SDH score (48.77%, 39.51% vs. 61.73%). CONCLUSIONS: Our logistic regression model and the SDH score based on 7 risk factors as right lower extremity, bilateral lower extremities, unprovoked, surgery or immobilization, malignant tumor, history of VTE, and D-dimer>1,000 ng/mL showed good calibration and discriminative power for the assessment of PE risk in patients with LDVT. The SDH score is more specific for PE prediction in the Chinese population, compared with the Wells score and the Revised Geneva score.

Application of critical water-alcohol composite medium to treat waste printed circuit boards: Oil phase products characteristic and debromination.

Critical water system used for decomposition and debromination of waste printed circuit board (PCBs) has two disadvantages: low value-added oil phase products and halfway debromination at low temperature condition. In this study, critical water-alcohol composite medium was found to be a promising method to surmount these disadvantages. Critical water-ethanol (CWE) and critical water-methanol (CWM) were selected as the composite medium. The temperature of CWE and CWM had a significant effect on the oil phase composition. At low temperature CWE/CWM of 300°C, 4-(1-methylethyl)-phenol with high concentration could be recovered. CWM of 400°C was beneficial to the generation of ether compounds and high level of anisole could be obtained, while 450°C was beneficial to the generation of high level of multi-alkyl substituted phenol derivatives or benzene derivatives such as p-xylene. Br-free oil phase products could be obtained when the temperature of CWE/CWM ≥300°C. Different oil phase products with high level of chemicals or chemical intermediates could be obtained by controlling the reaction conditions of CWE/CWM. It is believed that the additional value of the oil phase products derived from waste PCBs can be greatly improved by this new process.