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.

Global proteome and lysine succinylation analyses provide insights into the secondary metabolism in Salvia miltiorrhiza.

Danshen, belongs to the Lamiaceae family, and its scientific name is Salvia miltiorrhiza Bunge. It is a valuable medicinal plant to prevent and treat cardiovascular and cerebrovascular diseases. Lysine succinylation, a widespread modification found in various organisms, plays a critical role in regulating secondary metabolism in plants. The hairy roots of Salvia miltiorrhiza were subject to proteomic analysis to identify lysine succinylation sites using affinity purification and HPLC-MS/MS in this investigation. Our findings reveal 566 lysine succinylation sites in 348 protein sequences. We observed 110 succinylated proteins related to secondary metabolism, totaling 210 modification sites. Our analysis identified 53 types of enzymes among the succinylated proteins, including phenylalanine ammonia-lyase (PAL) and aldehyde dehydrogenase (ALDH). PAL, a crucial enzyme involved in the biosynthesis of rosmarinic acid and flavonoids, displayed succinylation at two sites. ALDH, which participates in the phenylpropane metabolic pathway, was succinylated at 8 eight sites. These observations suggest that lysine succinylation may play a vital role in regulating the production of secondary metabolites in Salvia miltiorrhiza. Our study may provide valuable insights for further investigation on plant succinylation, specifically as a reference point. SIGNIFICANCE: Salvia miltiorrhiza Bunge is a valuable medicinal plant that prevents and treats cardiovascular and cerebrovascular diseases. Lysine succinylation plays a critical role in regulating secondary metabolism in plants. The hairy roots of Salvia miltiorrhiza were subject to proteomic analysis to identify lysine succinylation sites using affinity purification and HPLC-MS/MS in this investigation. These observations suggest that lysine succinylation may act as a vital role in regulating the production of secondary metabolites in Salvia miltiorrhiza. Our study may provide valuable insights for further investigation on succinylation in plants, specifically as a reference point.

Impact of dialysis modality choice on the survival of end-stage renal disease patients with congestive heart failure in southern China: A retrospective cohort study.

Background and object: Heart failure is one of the common complications in patients with end-stage renal disease (ESRD) and a major cause of death in these patients. The choice of dialysis modality for ESRD patients with congestive heart failure (CHF) is still inconclusive. The purpose of this study was to compare the prognosis of hemodialysis (HD) and peritoneal dialysis (PD) among ESRD patients with CHF and provide a basis for clinical decision-making. Materials and methods: This was a retrospective study conducted at Guangdong Provincial Hospital of Traditional Chinese Medicine that included patients with CHF requiring long-term renal replacement therapy between January 1, 2012 and December 31, 2017. The end of follow-up was December 31, 2020. All patients were divided into HD and PD groups and sub grouped by age, and we used univariate and multifactorial Cox regression analyses to calculate the relative hazard ratios (HR) of the different dialysis types and adjusted for differences in baseline data using propensity score matching (PSM). Result: A total of 121 patients with PD and 156 patients with HD were included in this study. Among younger ESRD patients (≤65 years of age) with CHF, the prognosis of HD was worse than that of PD [HR = 1.84, 95% confidence interval (CI) = 1.01-3.34], and this disadvantage remained significant in the fully adjusted model [sex, age at dialysis initiation, Charlson comorbidities index, body mass index, prealbumin, hemoglobin, and left ventricular ejection fraction (LVEF)] and after PSM. In the older group (>65 years of age), the prognosis of HD was better than that of PD (HR = 0.46, 95% CI = 0.25-0.85), and the protective effect remained in the fully adjusted model and after PSM. The aforementioned survival differences across the cohort were maintained in patients with preserved LVEF (>55%), but could not be reproduced in patients with reduced LVEF (≤55%). Conclusion: In southern China, PD is a better choice for younger patients with ESRD, CHF and preserved LVEF, and HD is the better option for older patients.

Nutrient inputs from the leaf decay of Cynodon dactylon (L.) Pers in the water level fluctuation zone of a Three Gorges tributary.

Cynodon dactylon (L.) Pers (C. dactylon) is one of the dominant plants in the water level fluctuation (WLF) zone of the Three Gorges Reservoir (TGR) tributaries. However, the leaves of C. dactylon can decay to increase the inputs of nutrients under flood inundation, increasing the risk of eutrophication in the TGR tributaries. Nutrient inputs from the leaf decay of C. dactylon in three interfaces, namely, water-sediment (WS), water-C. dactylon (WC) and water-sediment-C. dactylon (W-S-C), were estimated in a 180 d inundation experiment. The results showed that the kinetic processes of total dissolved nitrogen (TDN) and total dissolved phosphorus (TDP) input accorded with the power function equation: y = axb for the WS, WC and W-S-C interfaces (R2s > 0.72, p < 0.001). The cumulative TDN input from leaf decay of C. dactylon in the WC interface was 506.44 mg N kg-1 of biomass, which was significantly higher than that in the W-S-C interface with 422.24 mg N kg-1 of biomass (p < 0.05). However, no significant differences in TDP input were found between the WC and W-S-C interfaces (p > 0.05). The total amounts of TDN and TDP inputs at the 165-175 m altitude were 21,688.81 and 13,121.68 kg year-1, respectively, which were approximately 3.17 times those from the 145-155 m altitude of the WLF zone. The amounts of TDN and TDP inputs from the leaves of C. dactylon for the whole WLF zone were 49,261.65 and 29,803.17 kg year-1, respectively, which were 0.1 and 2.7 times the annual permissible discharge amount of pollutants calculated from a municipal wastewater treatment plant with the peak flow of 60,000 m3/d according to Class I (A) of the Wastewater Discharge Standard (GB18918-2002) in China. Thus, the aboveground part of this perennial herb should be harvested in a timely manner before reflooding, especially at the higher altitudes of the WLF zone to decrease eutrophication risk.

Study on temporary resolution for offshore marine oil spill emergencies based on remote sensing system.

Time is particularly critical for an oil spill occurring in the ocean as wind and current can rapidly spread the oil over a large area in a short time. Using the features of sensor surveillance system and mathematical trajectory models, the cooperation of surveillance and trajectory under oil spill emergency response is presented in this paper. Based on integration of equation simulating an oil spill trajectory, the method for remote-sensing application time (Te) has been described, and optimization of processing time described in the application time equation has been proposed. This contribution, which is integrated with remote-sensing and mathematical models, is expected to be a powerful tool for real-time contingency planning in the Dalian Xingang oil spill. According to these findings, the method allowed spills emergency alerts to make the best decision for choosing remote-sensing data, considering effective temporary resolution.

Shenfu injection for intradialytic hypotension: a systematic review and meta-analysis.

Objective. To evaluate the effectiveness and safety of Shenfu injection (SFI) for intradialytic hypotension (IDH). Methods. A systematic review of data sources published as of April 2014 was conducted. These included the Cochrane Central Register of Controlled Trials (2014 issue 4), Pubmed, Embase, CBM, CNKI, VIP, and Wangfang Data. Randomized controlled trials (RCTs) involving SFI for treatment and prevention of IDH were identified. Two researchers independently selected articles, extracted data, assessed quality, and cross checked the results. Revman 5.2 was used to analyze the results. Results. Eight RCTs were included. The meta-analysis indicated that compared with conventional therapies alone, SFI could elevate systolic blood pressure (SBP), increase the clinical effective rate, decrease the incidence of hypotension, increase serum albumin (ALB) levels, and reduce C-reactive protein (CRP) levels without serious adverse effects. GRADE Quality of Evidence. the quality of SBP, the effective rate, ALB, and CRP were low, and hypotension incidence and DBP were very low. Conclusions. SFI is more effective than conventional therapies for prevention and treatment of IDH. However, a clinical recommendation is not warranted due to the small number of studies included and low methodology quality. Multi-center and high-quality RCTs with large sample sizes are needed to provide stronger evidence.