2,3,5,4'-Tetrahydroxy-stilbene-2-O-beta-d-glucoside induces autophagy-mediated apoptosis in hepatocytes by upregulating miR-122 and inhibiting the PI3K/Akt/mTOR pathway: implications for its hepatotoxicity.

CONTEXT: The potential hepatotoxicity of Polygoni Multiflori Radix (PMR) has attracted much attention, but the specific mechanism of inducing hepatotoxicity is still unclear due to the complexity of its components. OBJECTIVE: This study investigated the specific mechanism by which 2,3,5,4'-tetrahydroxy-stilbene-2-O-ß-d-glucoside (TSG) regulates hepatotoxicity. MATERIALS AND METHODS: The toxic effects of TSG (10, 100, 1000 µg/mL) on WRL-68 cells were examined using MTT, flow cytometry, and LDH assay after 24 h of incubation. Untreated cells served as the control. Gene and protein expression levels were determined by quantitative real-time PCR and Western blot, respectively. Immunofluorescence analysis was conducted to investigate the expression of light chain 3 (LC3). Luciferase activity assay was used to assess the targeted regulation of RUNX1 by miR-122. RESULTS: The half maximal inhibitory concentration (IC50) of TSG in WRL-68 cells was calculated as 1198.62 µg/mL. TSG (1000 µg/mL) inhibited cell viability and LDH activity and promoted WRL-68 cell apoptosis by inducing autophagy. Subsequent findings showed that TSG induced autophagy and promoted apoptosis in WRL-68 cells by downregulating the levels of p-PI3K, p-Akt, and p-mTOR proteins, while RUNX1 overexpression rescued this inhibition. Additionally, the effect of TSG on hepatocyte apoptosis was reversed by miR-122 knockdown. Furthermore, bioinformatics and dual luciferase reporter assay results indicated that miR-122 targeted RUNX1. DISCUSSION AND CONCLUSIONS: Our data demonstrate for the first time that TSG regulates hepatotoxicity, possibly by upregulating miR-122 and inhibiting the RUNX1-mediated PI3K/Akt/mTOR pathway to promote autophagy and induce hepatocyte apoptosis. Further in vivo research is necessary to verify our conclusion.

[Molecular mechanism of Mylabris for colorectal cancer based on integrative pharmacology].

At present, the disjointing situation is generally present between "systemic"and "local", "macro" and "micro", "in vivo process" and "activity evaluation" in the study of traditional Chinese medicine (TCM). An urgent task for the modernization of TCM is to establish new strategies and methods which can reflect the overall characteristics of TCM. The introduction of integrative pharmacology provided a feasible approach to solve the problem of the fragmentation of TCM. Internet-based computation platform method was adopted in this study to explore the active molecular mechanism of Mylabris in the treatment of colorectal cancer. Based on the analysis of the functional integration of internet-based computation platform V1.0 version software, the "core components-key target- main pathway" multidimensional network of Mylabris in treatment of colorectal cancer disease was constructed to explore the potential molecular mechanism of Mylabris in treatment of colorectal cancer from multiple perspectives. The results showed that Mylabris can treat the colorectal cancer and the mechanism might be associated with amino acid metabolism, NF-κB signaling pathway, immune system, endocrine system, nervous system, and chemokine signal transduction pathway, epithelial cell signaling in helicobacter pylori infection, T cell receptor signaling pathway, B cell receptor signaling pathway and so on.

[Correlation analysis of "compound-target-pathway" of Yinchenhao decoction for cirrhosis based on computed prediction].

Chinese medicine prescription is the main form and means to treat diseases in traditional Chinese medicine (TCM). However, the disjointing situation is generally present between "systemic" and "local", "macro" and "micro", "in vivo process" and "activity evaluation" in the study of TCM at present. An urgent task for the modernization of TCM is to establish new strategies and methods which can reflect the overall characteristics of TCM. The introduction of integrative pharmacology provided a feasible approach to solve the problem of the fragmentation of TCM. Internet-based computation platform method was adopted in this study to explore the active molecular mechanism of Yinchenhao decoction in the treatment of cirrhosis. Based on the analysis of the functional integration of Internet-based Computation Platform V1.0 version software, the "core components-key target- main pathway" multidimensional network of Yinchenhao decoction in treatment of cirrhosis disease was constructed to explore the potential molecular mechanism of Yinchenhao decoction in treatment of cirrhosis from multiple perspectives. The molecular mechanism analysis of Yinchenhao decoction showed that Yinchenhao decoction can achieve the therapeutic effect on cirrhosis and the mechanism might be associated with oxidative phosphorylation, energy metabolism, circulatory system, glycerophospholipid metabolis, lipid metabolism and other pathways. Yinchenhao decoction in treatment of cirrhosis may be associated with energy metabolism and lipid metabolism.

[UPLC-Q-TOF/MS for rapid analysis of chemical constituents in Sanhuang tablets].

The qualitative analysis method of ultra performance liquid chromatography tandem quadrupole time of flight mass spectrometry (UPLC-Q-TOF-MS/MS) was established for the chemical constituents in Sanhuang tablets. Waters ACQUITY BEH C18 (2.1 mm×100 mm, 1.7 µm) column was used with 0.1% formic acid solution (A)-0.1% formic acid acetonitrile (B) as the mobile phase for gradient elution. The flow rate was 0.2 mL•min⁻¹; the sample volume was 1 µL and the column temperature was 30 ℃. The high-resolution quadrupole time-flight mass spectrometry was used as detector with electrospray ion source in both positive and negative models, and the dry gas temperature was 325 ℃. Based on the analysis of mass spectrometry and literature reports, 38 compounds were confirmed, including 1 alkaloid, 1 dianthrone compound, 6 tannins, 7 anthraquinone glycosides, 6 anthraquinones and 17 flavonoids. Liquid chromatography-mass spectrometry method is simple, reliable and rapid to identify the chemical compositions of Sanhuang tablets, and it is helpful to reveal its chemical constituents and pharmacodynamic substances.

The development of logic gate-based fluorescent probes that respond to intracellular hydrogen peroxide and pH in tandem.

Logic gate-based fluorescent probes are powerful tools for the discriminative sensing of multiple signaling molecules that are expressed in concert during the progression of many diseases such as inflammation, cancer, aging, and other disorders. To achieve logical sensing, multiple functional groups are introduced to the different substitution sites of a single fluorescent dye, which increases the complexity of chemical synthesis. Herein, we report a simple strategy that incorporates just one responsive unit into a hemicyanine dye achieving the logic gate-based sensing of two independent analytes. We introduce boronic acid to hemicyanine to quench the fluorescence, and in the presence of hydrogen peroxide (H2O2), the fluorescence is recovered due to removal of the boronate. Interestingly, the subsequent decrease in pH turned the red fluorescence of hemicyanine to green emissive because of protonation of the phenolic alcohol. This unique feature of the probe enables us to construct "INHIBIT" and "AND" logical gates for the accurate measuring of intracellular H2O2 and acidic pH in tandem. This study offers insight into the simple construction of logic-gate based fluorescent probes for the tandem sensing of multiple analytes that are correlatively produced during disease progression.

Improved inhibitory activities against tumor-cell migration and invasion by 15-benzylidene substitution derivatives of andrographolide.

In the present study, andrographolide (Andro, 1) derivatives were screened to identify potent inhibitors against tumor-cell migration and invasion, and associated structure-activity relationships were studied. Compared to 1, compounds 8a-8d exhibited more potent activities against migration in SGC-7901, PC-3, A549, HT-29 and Ec109 cell lines. Improved activities against tumor-cell migration and invasion were proved to be associated with the down-regulation of MMPs.

Fluorescence-based chemical tools for monitoring ultrasound-induced hydroxyl radical production in aqueous solution and in cells.

We report the synthesis of hydroxyl-radical (˙OH) responsive fluorescent probes that utilise the 3,5-dihydroxybenzyl (DHB) functionality. 4-Methylumbeliferone-DHB (Umb-DHB) and resorufin-DHB (Res-DHB) in the presence of ˙OH radicals resulted in significant increases in their respective fluorescent emission intensities at 460 nm and 585 nm. The incubation of Res-DHB in HeLa cells followed by therapeutic ultrasound (1 MHz) resulted in a significant increase in fluorescence emission intensity thus permitting the ability to monitor ultrasound-induced ˙OH production in live cells.

Unhealthy Lifestyles and Retinal Vessel Calibers among Children and Adolescents: A Systematic Review and Meta-Analysis.

The retinal vessel caliber (RVC) is an important biomarker of cardiovascular diseases, which can be semi-automatically measured by fundus photography. This review investigated the associations between the RVCs and the life styles of early life, such as physical activity (PA), sedentary behavior (SB), dietary and sleep, by summarizing the findings from studies on children and adolescents. Two databases (Medline and Embase) were searched from their inception to 30 June 2022. The selected studies were literatures on observational designs, fundus photographs, retinal vessels and lifestyles of children or adolescents. Correlation coefficients of unhealthy life styles and RVCs were transformed to Fisher's z-scores, and the random-effects model was applied to pool data. A total of 18 observational studies were selected; the lifestyles accessed include 9 studies for PA and SB, 8 studies for dietary and 1 study for sleep. The meta-analysis on the correlation coefficients of regression models found the high level of SB (qualified by screen time, ST) was associated the narrower central retinal arteriolar equivalent (CRAE) among children (r = -0.043, 95% confidence intervals [CI] -0.078 to -0.009). By comparing the first and fourth quartiles of PA, the meta-analysis showed that more indoor PA was associated with smaller venular calibers and more outdoor PA was associated with wider CRAE (r = 0.88, 95%CI -3.33 to 0). Unhealthy lifestyles might be harmful on the retinal microcirculation among children and adolescents but their health effect seems not to be as significant as those in adults.

Poloxamer modified florfenicol instant microparticles for improved oral bioavailability.

Surfactants can improve the hydrophobicity of poorly water-soluble drugs and increase the stability of microparticles by reducing surface tension. This study describes that surfactant-engineered florfenicol instant microparticles (FIMs) increase bioavailability through a micellar solubilization mechanism. The FIMs were prepared by a modified emulsification method, and the optimal prescription was obtained by a combination of single factor investigation and response surface methodology. The microparticles prepared in this study reduce the polymer materials while increasing the drug content. FIM has a smaller particle size and modification of poloxamer, resulting in better solubility and higher bioavailability. The in vitro solubility of FIM is 1.43 times higher than that of the bulk drug, and the dissolution equilibrium can be achieved in 10 minutes. Compared with florfenicol, FIM showed a decrease in Tmax in the plasma concentration curve, with a peak concentration of 1.43 times and an area of 1.41 times. Considering the advantages of in vitro/in vivo performance and ease of preparation, FIMs may have great application prospects in pharmacy research.

[Degradation Process of Exogenous Naphthenic Acids and Their Effects on Microbial Community Structure in Soil].

Naphthenic acids (NAs) are a natural component of petroleum, which account for about 2% of severe ecological toxicity in addition to polycyclic aromatic hydrocarbons. With the growth in demand for energy, a large number of NAs have leaked into soil environments through oil industry processes, which have caused enormous potential threats to human health and ecosystems. However, there are few studies about the degradation process of exogenous NAs and their effects on microbial community structures in soil. This research explores the degradation process of NAs and their dynamics in microbial communities in soil by adding a high concentration of 180 mg·kg-1 of NAs to natural, clean soil with the aid of liquid chromatography and high-throughput sequencing technologies. This study found that:① Natural clean soil has a strong capability to degrade high concentration of NAs with about 50% of the NAs degraded within 5 days, which stabilized at 80% after 30 days of the experiment; ② Pollution with NAs obviously alters the microbial community structure as the number of specific OTU increased and were mainly distributed in phylum of unidentified Proteobacteria and Bacteroidetes; ③ Under high concentrations of NAs, the content of Bacteroidetes and Acidobacteria phylum and the γ-Proteobacteria of Proteobacteria phylum all increased swiftly and were speculated to be a potential agents for NA degradation, with the relative abundance ratio of Bacteroidetes and Acidobacteria increasing from 4.2% and 2% to 20.3% and 5.5%, respectively, while a 24.8% decrease was found in Actinobacteria phylum; ④ This study revealed the degradation process of exogenous NAs and their effects on microbial community structure in soil, which provided scientific support for the ecological restoration of petroleum pollution and further study in this area.

[Effect of agricultural application of municipal sewage sludge on plant-soil system: A review]. / 城市污泥农用对植物-土壤系统的影响.

Currently, reasonable disposal of municipal sewage sludge is one of the important issues in the field of resources and environmental science. Sludge is rich in large amounts of organic matter and available nutrients, promoting soil fertility, soil physical structure and biological properties. However, sludge contains a variety of heavy metals, organic contaminants and other hazardous substance, especially heavy metals, which are the bottlenecks of agricultural application of sludge. To improve the sewage sludge utilization efficiency and decrease the effect on soil, this essay made a summary on domestic and foreign studies on plant-soil interaction ecosystem with sewage sludge to provide a theoretical basis and scientific guidance for advancing sewage sludge utilization efficiency.

[Fluorescence Properties of Glomalin and Its Relationship with Soil Physyicochemical Characteristics in Different Regions of Beijing City].

Glomalin-related soil proteins (GRSP), which has been used as a presumable biological indicator of soil quality, is of vital ecological importance. In this research, we tested the GRSP content and physicochemical property of soils collected in mountain, urban and suburb areas of Beijing City. Besides, the fluorescence property of GRSP was also studied by using EEM-PARAFAC. The results showed that GRSP could be decomposed into five compounds, terrestrial humic-like substances UVA, terrestrial humic-like substances UVC, oxidized quinones, soil fulvic acid and amino acids. The GRSP content and protein-like fluorescence substances in urban and suburb areas significant decreased and oxidized quinones content elevated in comparison with those in mountain area. The physicochemical property was also shaped by urbanization. Compare to mountain area, moisture content, total organic matters and total nitrogen significantly decreased in urban area soil and suburb area. GRSP content, terrestrial humic-like substances UVA and oxidized quinones content showed significant correlation with soil organic matter and total nitrogen. Base on that, an integrated index system mainly consisting of GRSP concentration and C1 component and C3 component was recommended to evaluate the soil health status.

A Correlation Study of DHA Dietary Intake and Plasma, Erythrocyte and Breast Milk DHA Concentrations in Lactating Women from Coastland, Lakeland, and Inland Areas of China.

We aimed to assess the correlation between docosahexaenoic acid (DHA) dietary intake and the plasma, erythrocyte and breast milk DHA concentrations in lactating women residing in the coastland, lakeland and inland areas of China. A total of 408 healthy lactating women (42 ± 7 days postpartum) were recruited from four hospitals located in Weihai (coastland), Yueyang (lakeland) and Baotou (inland) city. The categories of food containing DHA, the average amount consumed per time and the frequency of consumption in the past month were assessed by a tailored DHA food frequency questionnaire, the DHA Intake Evaluation Tool (DIET). DHA dietary intake (mg/day) was calculated according to the Chinese Food Composition Table (Version 2009). In addition, fasting venous blood (5 mL) and breast milk (10 mL) were collected from lactating women. DHA concentrations in plasma, erythrocyte and breast milk were measured using capillary gas chromatography, and were reported as absolute concentration (µg/mL) and relative concentration (weight percent of total fatty acids, wt. %). Spearman correlation coefficients were used to assess the correlation between intakes of DHA and its concentrations in biological specimens. The study showed that the breast milk, plasma and erythrocyte DHA concentrations were positively correlated with DHA dietary intake; corresponding correlation coefficients were 0.36, 0.36 and 0.24 for relative concentration and 0.33, 0.32, and 0.18 for absolute concentration (p < 0.05). The median DHA dietary intake varied significantly across areas (p < 0.05), which was highest in the coastland (24.32 mg/day), followed by lakeland (13.69 mg/day), and lowest in the inland (8.84 mg/day). The overall relative and absolute DHA concentrations in breast milk were 0.36% ± 0.23% and 141.49 ± 107.41 µg/mL; the concentrations were significantly lower in inland women than those from coastland and lakeland. We conclude that DHA dietary intake is positively correlated with DHA concentrations in blood and breast milk in Chinese lactating women, suggesting that the tailored DHA food frequency questionnaire, DIET, is a valid tool for the assessment of DHA dietary intake.

[Comparing Cell Toxicity of Schizosaccharomyces pombe Exposure to Airborne PM2.5 from Beijing and Inert Particle SiO2].

To figure out the main factor of PM2.5 toxicity to cell, this study compared the cell toxicity of Schizosaccharomyces pombe (S. pombe), a model organism, exposed to inert ultrafine SiO2 particles, a model particle, and airborne PM2.5 collected from campus of Peking University Beijing China. Using ultraviolet spectrophotometry to measure cell proliferation ratio, and environmental scanning microscope to observe the particle adhesion on the cell surface, and detecting cellular ROS generation with DHE fluorescent dye chromogenic method, and using single cell gel electrophoresis to test cell DNA damage, the experiment results indicated that the ultrafine SiO2 particles (< 60 nm) could inhibit the cell proliferation of S. pombe, mainly through adsorbing onto the cell surface to change the permeability of the cell wall; but it could not induce cells to generate ROS to cause the oxidative damage. PM2.5, the average particle size of which was larger than that of SiO2 particles, could cause oxidative damages to cells mainly by inducing cells to generate ROS, and damage DNA simultaneously. It might illustrate that there was no direct relationship between the toxicity of PM2.5 and its physical properties such as the particle size.

Preparation of cefquinome sulfate proliposome and its pharmacokinetics in rabbit.

Cefquinome Sulfate (CS) is a fourth-generation cephalosporin, which has been developed solely for veterinary use. It shows potent antibacterial activity against a broad spectrum of bacterial species. However, Cefquinome is susceptible to hydrolysis, which limiting its clinical employment efficacies to some extent. So, in this study, to increase Cefquinome Sulfate biological half-life, a novel Cefquinome Sulfate proliposome was prepared by solid dispersion and effervescent techniques and characterized for morphology, particle size, entrapment efficiency and in vitro release. A Reversed Phase-High Performance Liquid Chromatography (RP-HPLC) method was first chosen and established to determine the drug concentration in plasma after intra muscular (IM) administrating Cefquinome Sulfate solution and liposome at a single dosage of 18 mg/kg in rabbit. Then their pharmacokinetics in vivo was compared. Results showed that the received liposome was milky white suspension, spherical or ellipsoidal in shape. The mean particle size was 203±5 nm and the entrapment efficiency was 53.5±0.16%. The cefaquinom sulfate solution and liposome both followed a two compartment model, in vivo. The pharmacokinetic parameters for the solution and liposomal formulations were measured as follows: t1/2 α were (1.214 ± 0.135) h and (1.395 ± 0.113) h, t1/2 ß were (8.752 ± 0.846) h and (16.503 ± 1.275) h, AUC(0-24) were (49.582 ± 9.173) (mg·h)/L and (138.727 ± 11.034) (mg·h)/L, CL/F were (0.357 ± 0.015) L/(h·kg) and (0.127 ± 0.012) L/(h·kg), MRT(0-24) were (2.68 ± 0.229) h and (5.945 ± 0.479) h, respectively. It could be clearly seen that t1/2 ß of liposome prolonged (p < 0.05), AUC and MRT both increased remarkably (p < 0.01), CL/F decreased. Results indicated that this preparation has more residence time and exhibits some sustained-release tendency.