Resveratrol Enhances Anticancer Effects of Silybin on HepG2 Cells and H22 Tumor-bearing Mice via Inducing G2/M Phase Arrest and Increasing Bax/Bcl-2 Ratio.

BACKGROUND: Silybin, a major flavonoid extracted from the seeds of milk thistle, has a strong hepatoprotective but weak anti-hepatoma activity. Screening another natural ingredient and combining it with silybin is expected to improve the anti-hepatoma efficacy of silybin. OBJECTIVE: The objective of this study was to investigate the synergistic anti-hepatoma effect of resveratrol and silybin on HepG2 cells and H22 tumor-bearing mice in hepatocellular carcinoma (HCC) in vitro and in vivo, respectively. METHODS: Cell viability, scratch wound, clone formation, cell apoptosis, cell cycle, and western blot analysis of HepG2 cells were used to investigate the synergistic effects in vitro of the combination resveratrol with silybin. Growth rates, tumor weights, organ indexes, and histological pathological examination in H22 tumor-bearing mice were used to investigate the synergistic effects in vivo. RESULTS: The combination of resveratrol (50 µg/mL) and silybin (100 µg/mL) significantly suppressed cell viability, whose combination index (CI) was 1.63 (>1.15), indicating the best synergism. The combination exhibited the synergistic effect in blocking the migration and proliferative capacity of HepG2 cells in the measurement in vitro. In particular, resveratrol enhanced the upregulation of Bcl-2 expression and the downregulation of Bax expression with a concurrent increase in the Bax/Bcl-2 ratio. The combination of resveratrol (50 mg/kg) and silybin (100 mg/kg) reduced the tumor weight, inhibited the growth rate, increased the organ indexes, and destroyed the tumor tissue morphology in H22 tumor-bearing mice. CONCLUSION: Resveratrol was found to exhibit synergistic anti-cancer effects with silybin on HepG2 cells and H22 tumor-bearing mice.

QEEG indices are associated with inflammatory and metabolic risk factors in Parkinson's disease dementia: An observational study.

Background: Quantitative electroencephalography (QEEG) is a reliable and non-invasive diagnostic tool to quantify cortical synaptic injury or loss in the clinical assessment of neurodegenerative diseases, and may be able to differentiate various types of dementia. We investigated if QEEG indices can differentiate Parkinson's Disease (PD) with nondementia (PD-ND) from PD with dementia (PDD), and to determine if QEEG indices correlate with inflammation and lipid metabolism markers in PD. Methods: This clinical study collected data between July 1, 2018 and July 1, 2021 in Zhujiang Hospital of Southern Medical University in China and data was analysed. A total of 125 individuals comprising of 31 PDD, 47 patients with PD-ND and 47 healthy controls were included. We calculated the absolute spectral power (ASP) of frequency bands and the slow-to-fast frequency ratios of specific brain regions. Plasma levels of hypersensitive C-reactive protein (Hs-CRP), superoxide dismutase (SOD), and high-density lipoprotein cholesterol (HDL-C) were measured and correlations with QEEG indices were examined. Findings: A significantly higher ASP of delta frequency especially in the frontal region was observed in patients with PDD compared to PD-ND (P=0.004) and controls (P=0.000). Decreased HDL-C (OR=0.186, P=0.030), and increased Hs-CRP (OR =2.856, P=0.015) were associated with PDD. Frontal-delta ASP was negatively correlated with plasma HDL-C (r=-0.353, P=0.000) and SOD (r=-0.322, P=0.001), and positively correlated with Hs-CRP (r=0.342, P=0.000). Interpretation: We highlight novel correlations between QEEG indices and inflammation and lipid metabolism markers in PD-ND and PDD. QEEG indices, HDL-C and Hs-CRP are potentially useful for the evaluation of PDD. Our current findings suggest that peripheral inflammation might contribute to the pathogenesis of cognitive impairment and EEG slowing in PDD. The mechanism underlying frontal-delta ASP and its correlation with neuro-inflammatory and metabolic markers in PDD should be further investigated. Funding: The National Natural Science Foundation of China (NO: 81873777, 82071414); the Scientific Research Foundation of Guangzhou (NO: 202206010005); the Science and Technology Program of Guangdong of China (NO: 2020A0505100037); the High-level Hospital Construction Research Project of Maoming People's Hospital (NO: xz2020009); the Science and Technology Program of Maoming City (NO: 2021S0026). Dr EK Tan is supported by the National Medical Research Council, Singapore.

One-step preparation of Fe/N co-doped porous biochar for chromium(VI) and bisphenol a decontamination in water: Insights to co-activation and adsorption mechanisms.

Herein, magnetic nitrogen doped porous biochar (Fe/N-PBC) was prepared by mixing KHCO3, K2FeO4 and CO(NH2)2 through one-step pyrolysis, and was employed for adsorbing Cr(VI) and BPA in water. The whole co-activated process was accompanied with pore-forming, carbon thermal reduction and element doping. Specifically, the developed microporous structures and high surface area of Fe/N-PBC (1093.68 m2/g) were achieved under synergistic activation of KHCO3 and K2FeO4. Meanwhile, carbon thermal reduction process successfully converted K2FeO4 to Fe0 with introduction of heterocyclic-N (pyrrolic N and pyridinic N) structures by CO(NH2)2 doping. Fe/N-PBC exhibited outstanding uptake for Cr(VI) (340.96 mg/g) and BPA (355.14 mg/g), and possessed favorable regeneration properties after three cycles. Notably, the high-performance Cr(VI) removal was associated to reduction, electrostatic interaction, complexation, pore filling and ion exchange, while pore filling, hydrogen-bonding interaction and π-π stacking were responsible for BPA binding. This work presents reasonable design of Fe/N-carbon materials for Cr(VI)/BPA polluted water remediation.

Ball milling potassium ferrate activated biochar for efficient chromium and tetracycline decontamination: Insights into activation and adsorption mechanisms.

Herein, novel Fe-biochar composites (MBCBM500 and MBCBM700) were synthesized through K2FeO4 co-pyrolysis and ball milling, and were used to eliminate Cr(VI)/TC from water. Characterization results revealed that higher temperature promoted formation of zero-valent iron and Fe3C on MBCBM700 through carbothermal reduction between K2FeO4 and biochar. The higher specific surface area and smaller particle size of MBCBM500/700 stemmed from the corrosive functions of K and the ball milling process. And the maximal uptake amount of MBCBM700 for Cr(VI)/TC was 117.49/90.31 mg/g, relatively higher than that of MBCBM500 (93.86/84.15 mg/g). Furthermore, ion exchange, pore filling, precipitation, complexation, reduction and electrostatic attraction were proved to facilitate the adsorption of Cr(VI), while hydrogen bonding force, pore filling, complexation and π-π stacking were the primary pathways to eliminate TC. This study provide a reasonable design of Fe-carbon materials for Cr(VI)/TC contained water remediation, which required neither extra modifiers nor complex preparation process.

Concurrent elimination and stepwise recovery of Pb(II) and bisphenol A from water using ß-cyclodextrin modified magnetic cellulose: adsorption performance and mechanism investigation.

Coexistence of heavy metals and endocrine disrupting compounds in polluted water with competitive adsorption behavior necessitates design of tailored adsorbents. In this work, ß-cyclodextrin modified magnetic rice husk-derived cellulose (ß-CD@MRHC) which can provide independent functional sites for effectively binding the above two types of contaminants was synthesized and used for Pb(II) and BPA elimination in both unit and multivariate systems. Characterizations results confirmed successful ß-CD grafting and Fe3O4 loading, and the ß-CD@MRHC had excellent magnetic property for its effectively recovery from water, which was not affected by the adsorption of pollutants. The ß-CD@MRHC possessed superior adsorption performance with maximal Pb(II)/BPA uptake of 266.2 or 412.8 mg/g, severally, and the adsorption equilibrium was fleetly reached in 30 and 7.5 min. Moreover, the ß-CD@MRHC could accomplish synergetic Pb(II) and BPA elimination through averting their competitive behaviors owing to diverse capture mechanisms for Pb(II) (ion exchange, complexation and electrostatic attraction) and BPA (hydrogen bonding and host-guest inclusion). Furthermore, after three cycles of step-wise desorption, the binding of Pb(II) as well as BPA byß-CD@MRHC dropped slightly in dualistic condition. In summary, ß-CD@MRHC was a promising tailored adsorbent to practical application for simultaneously removing heavy metals and organic matters from wastewater with high-performance magnetic recovery.

Cerebral Circulation Time Is a Potential Predictor of Disabling Ischemic Cerebrovascular Events in Patients With Non-disabling Middle Cerebral Artery Stenosis.

Patients with non-disabling middle cerebral artery (MCA) stenosis (ND-MCAS) are at risk for disabling ischemic cerebrovascular events (DICE) despite aggressive medical therapy. In this study, we aimed to verify whether cerebral circulation time (CCT) was a potential predictor of DICE in patients with ND-MCAS. From January 2015 to January 2020, 46 patients with ND-MCAS treated with aggressive medical therapy were enrolled for digital subtraction angiography (DSA) in this convenience sampling study. They were divided into the DICE (-) and DICE (+) groups based on the occurrence of DICE within 3 months after DSA. The CCT was defined as the time from the appearance of the MCA to the peak intensity of the Trolard vein during DSA. The rCCT (relative CCT) was defined as the ratio of the CCT of the stenotic side (sCCT) to the CCT of the healthy side (hCCT). The differences in sCCT, hCCT, and rCCT between the two groups were analyzed with Mann-Whitney U tests. Logistic regression analysis was performed to evaluate the association between the risk factors and DICE. Receiver operating characteristic (ROC) curves were constructed to assess the predictive value of rCCT in identifying DICE in ND-MCAS patients. The results showed that DICE appeared in 5 of the 46 patients within 3 months. rCCT were significantly increased in the DICE (+) group compared with the DICE (-) group [1.08 (1.05, 1.14) vs. 1.30 (1.22, 1.54), p < 0.001]. Logistic regression analysis found that prolonged rCCT was an independent positive prognostic factor for DICE (odds ratio = 1.273, p = 0.019) after adjustment for potential confounders (age, diabetes, antithrombotic use, and stenosis degree). ROC analysis showed that rCCT provided satisfactory accuracy in distinguishing the DICE (+) group from the DICE (-) group among ND-MCAS patients (area under the curve = 0.985, p < 0.001), with an optimal cutoff point of 1.20 (100% sensitivity, 97.6% specificity). In conclusion, prolonged rCCT is independently associated with the occurrence of DICE in ND-MCAS patients and may be used to identify individuals at risk of DICE.

Cystatin C is a potential predictor of unfavorable outcomes for cerebral ischemia with intravenous tissue plasminogen activator treatment: A multicenter prospective nested case-control study.

BACKGROUND AND PURPOSE: The aim of this study was to explore whether cystatin C (CysC) could be used as a potential predictor of clinical outcomes in acute ischemic stroke (AIS) patients treated with intravenous tissue plasminogen activator (IV-tPA). METHODS: We performed an observational study including a retrospective analysis of data from 125 AIS patients with intravenous thrombolysis. General linear models were applied to compare CysC levels between groups with different outcomes; logistic regression analysis and receiver-operating characteristic curves were adopted to identify the association between CysC and the therapeutic effects. RESULTS: Compared with the "good and sustained benefit" (GSB) outcome group (defined as ≥4-point reduction in National Institutes of Health Stroke Scale or a score of 0-1 at 24 h and 7 days) and the "good functional outcome" (GFO) group (modified Rankin Scale score 0-2 at 90 days), serum CysC baseline levels were increased in the non-GSB and non-GFO groups. Logistic regression analysis found that CysC was an independent negative prognostic factor for GSB (odds ratio [OR] 0.010; p = 0.005) and GFO (OR 0.011; p = 0.021) after adjustment for potential influencing factors. Receiver-operating characteristic curves showed the CysC-involved combined models provided credible efficacy for predicting post-90-day favorable clinical outcome (area under the curve 0.86; p < 0.001). CONCLUSIONS: Elevated serum CysC is independently associated with unfavorable clinical outcomes after IV-tPA therapy in AIS. Our findings provide new insights into discovering potential mediators for neuropathological process or treatment in stroke.