Delisheng, a Chinese medicinal compound, exerts anti-proliferative and pro-apoptotic effects on HepG2 cells through extrinsic and intrinsic pathways

The anti-proliferative, cytotoxic and apoptogenic activities of delisheng, a Chinese medicinal compound, has been investigated. In this study, the hepatocarcinoma cell line (HepG2) and the liver cell line (L-02) were exposed to delisheng (6.25, 50 and 100 μl/ml). Delisheng suppressed the proliferation and viability of normal liver L-02 cells slightly, but strongly inhibited the proliferation and viability of hepatocarcinoma HepG2 cells. The flow cytometric analysis of HepG2 cells demonstrated that delisheng primarily arrested the HepG2 cells at the G1 phase of the cell cycle. Annexin V-FITC/PI staining corroborates the apoptogenic nature of delisheng on HepG2 cells. The anti-proliferative and pro-apoptotic effect of delisheng in HepG2 cells was associated with changes in the Bcl-2/Bax ratio and the induction of caspase-mediated apoptosis. Upregulation of DR5 expression was observed in HepG2 cells after treatment with delisheng. The findings from the present study suggest that delisheng has selective cytotoxic activities against HepG2 cells. Delisheng triggered time- and dose-dependent apoptosis in HepG2 cells by activating the mitochondria-mediated and death receptor-mediated apoptotic pathways

Anticancer Effects of Chenopodium ambrosiodes L. Essential Oil on Human Breast Cancer MCF-7 Cells In vitro

Purpose: To investigate the most effective compound of C. ambrosioides essential oil for the induction of cell death in human breast cancer cells (MCF-7), and the mechanism of induction.Methods: MCF-7 cells were treated with essential oil and its two main components, 1-isopropyl-4- methylbenzene and α-terpinene, respectively, for 24 and 48 h in vitro. To determine their cytotoxicity on MCF-7 cells, in vitro cytotoxicity, 3-(4, 5-dimethylthaizol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and live/dead cell fluorescent staining were used. MCF-7 cellular superoxide dismutase (SOD), catalase (CAT) vitality and malondialdehyde (MDA) content were also evaluated.Results: MTT results showed that essential oil and its two main compositions significantly inhibited the growth of MCF-7 cells in 24 h (p < 0.05), which was consistent with the Live/dead cell fluorescent staining results. After 24 h incubation the average inhibition rate is 58.98 % for essential oil, 37.8 % for 1-isopropyl-4-methylbenzene and 32.09 % for α-terpinene. With increase in the concentration of essential oil and the two main components, the relative activity of SOD significantly decreased (p < 0.05), while the relative activity of CAT was gradually increased (p < 0.05), compared with control. MDA relative content significantly increased (p < 0.05) until the concentration was 1.25, 0.21 and 0.17 μg/ml for essential oil , 1-isopropyl-4-methylbenzene and α-terpinene , and thereafter significantly decreased (p < 0.05) , compared to control.Conclusion: The data suggest that the essential oil of C. ambrosioides and its two main components inhibit MCF-7 cell proliferation cell death by inducing oxidative damage. However, the two main components are less effective in their anticancer activity than the essential oilKeywords: Chenopodium ambrosioides L. Essential oil, 1-isopropyl-4-methylbenzene, α-Terpinene, Breast cancer MCF-7 cells, Antitumor activit

Overproduction of Mitochondrial Fission Proteins in Membranous Nephropathy in Children

Background/Aims: The molecules involved in nephrotic syndrome (NS) have not been fully clarified. Mitochondrial fission proteins are found to be involved in podocyte injury in vitro. Increased glomerular expression of mitochondrial fission proteins was found in adriamycin nephropathy in our previous study. Whether or not mitochondrial fission proteins are involved in podocyte injury in NS is not clear. This study explored the glomerular expression and possible pathological significance of mitochondrial fission-associated proteins, including dynamin-related protein 1 (Drp1) and mitochondrial fission protein 1 (Fis1), in children with NS. Methods: Eighteen children with primary NS, including 6 with minimal change disease, 6 with focal segmental glomerulosclerosis, 6 with membranous nephropathy, 6 children with isolated haematuria and 3 normal controls were included. The glomerular expression of Drp1, phospho-Drp1 (Ser616) and Fis1, urinary protein measurements, and podocyte mitochondrial density under electron microscopy were investigated and compared. Results: Glomerular expression of Drp1, phospho-Drp1 (Ser616) and Fis1 was mainly increased in children with NS with membranous nephropathy. No relationship was found between glomerular expression of Drp1, phospho-Drp1 (Ser616) and Fis1 and podocyte mitochondrial density or urinary protein measurements. Conclusion: Glomerular overproduction of Drp1, phospho-Drp1 (Ser 616) and Fis1 occurred mainly in children with membranous nephropathy. The pathological significance deserves further investigation

In vitro antioxidant, antibacterial and anti-tumor activities of total flavonoids from Elsholtzia densa Benth

Purpose: To investigate the in vitro antioxidant, antibacterial and anti-tumor activities of total flavonoids from Elsholtzia densa Benth of Sichuan Province, China. Methods: The total flavonoids of Elsholtzia densa Bent were extracted utilizing the ultrasonic extraction method, and purified by D101 macroporous adsorption resin. An in vitro antioxidant test, 3-(4,5dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay and iCELLigence system were used to evaluate their antioxidant, antibacterial and anti-tumor activities. Results: The results showed that the total flavonoids exhibited good scavenging ability in hydroxyl radical (•OH), DPPH free radical (DPPH•), and super oxide anion radical (O2-•). Antioxidant activity was higher than for control (ascorbic acid). Their antibacterial activity was good with minimum inhibitory concentration (MIC) of 2, 4 and 14 μg/mL against Escherichia coli, Staphylococcus aureus and Bacillus subtilis, respectively. Anti-proliferation data from the iCELLigence system studies showed that the total flavonoids significantly inhibited the growth of five types of cells, including a normal human hepatocytes cell line (L02), two human hepatocellular carcinoma cell line (SMMC-7721 and HepG-2), a human cervical cancer cell line (Hela) and a Baby Hamster Syrian Kidney cell line (BHK-21) (p < 0.05). AO/EB staining indicate that the total flavonoids might cause apoptosis of Hela cells. Conclusion: The results suggest that the total flavonoids from Elsholtzia densa Bent are potential natural antioxidants and antimicrobial agent, with anti-cancer properties. Keywords: Elsholtzia densa Benth., Total flavonoids, Antioxidant activity, Antibacterial activity, Antitumor activit

Effects of Yulin Tong Bu formula on modulating gut microbiota and fecal metabolite interactions in mice with polycystic ovary syndrome

BackgroundPolycystic ovarian syndrome (PCOS) is a common endocrine disorder characterized by hyperandrogenism, ovarian dysfunction and polycystic ovarian morphology. Gut microbiota dysbiosis and metabolite are associated with PCOS clinical parameters. Yulin Tong Bu formula (YLTB), a traditional Chinese medicine formula, has been recently indicated to be capable of ameliorating polycystic ovary symptoms and correcting abnormal glucose metabolism. However, the therapeutic mechanism of YLTB on PCOS has not been fully elucidated.MethodsA pseudo sterile mouse model was established during this four-day acclimatization phase by giving the animals an antibiotic cocktail to remove the gut microbiota. Here, the therapeutic effects of YLTB on PCOS were investigated using dehydroepiandrosterone plus high-fat diet-induced PCOS mice model. Female prepuberal mice were randomly divided into three groups; namely, the control group, PCOS group and YLTB (38.68 g·kg-1·day-1) group. To test whether this effect is associated with the gut microbiota, we performed 16S rRNA sequencing studies to analyze the fecal microbiota of mice. The relationships among metabolites, gut microbiota, and PCOS phenotypes were further explored by using Spearman correlation analysis. Then, the effect of metabolite ferulic acid was then validated in PCOS mice.ResultsOur results showed that YLTB treatment ameliorated PCOS features (ovarian dysfunction, delayed glucose clearance, decreased insulin sensitivity, deregulation of glucolipid metabolism and hormones, etc.) and significantly attenuated PCOS gut microbiota dysbiosis. Spearman correlation analysis showed that metabolites such as ferulic acid and folic acid are negatively correlated with PCOS clinical parameters. The effect of ferulic acid was similar to that of YLTB. In addition, the bacterial species such as Bacteroides dorei and Bacteroides fragilis were found to be positively related to PCOS clinical parameters, using the association study analysis.ConclusionThese results suggest that YLTB treatment systematically regulates the interaction between the gut microbiota and the associated metabolites to ameliorate PCOS, providing a solid theoretical basis for further validation of YLTB effect on human PCOS trials

Regulation of autophagy and lipid accumulation under phosphate limitation in Rhodotorula toruloides

BackgroundIt is known that autophagy is essential for cell survival under stress conditions. Inorganic phosphate (Pi) is an essential nutrient for cell growth and Pi-limitation can trigger autophagy and lipid accumulation in oleaginous yeasts, yet protein (de)-phosphorylation and related signaling events in response to Pi limitation and the molecular basis linking Pi-limitation to autophagy and lipid accumulation remain elusive.ResultsHere, we compared the proteome and phosphoproteome of Rhodotorula toruloides CGMCC 2.1389 under Pi-limitation and Pi-repletion. In total, proteome analysis identified 3,556 proteins and the phosphoproteome analysis identified 1,649 phosphoproteins contained 5,659 phosphosites including 4,499 pSer, 978 pThr, and 182 pTyr. We found Pi-starvation-induced autophagy was regulated by autophagy-related proteins, but not the PHO pathway. When ATG9 was knocked down, the engineered strains produced significantly less lipids under Pi-limitation, suggesting that autophagy required Atg9 in R. toruloides and that was conducive to lipid accumulation.ConclusionOur results provide new insights into autophagy regulation under Pi-limitation and lipid accumulation in oleaginous yeast, which should be valuable to guide further mechanistic study of oleaginicity and genetic engineering for advanced lipid producing cell factory

A novel scoring system for the quantitative prediction of prognosis in acute myeloid leukemia

BackgroundAcute myeloid leukemia (AML) is a heterogeneous hematopoietic malignancy. Patient prognosis cannot be accurately assessed in National Comprehensive Cancer Network (NCCN) risk stratification subgroups based on the current criteria. This study aimed to develop a novel prognostic score model for the quantitative prediction of prognosis in AML.ResultsWe developed a prognostic risk scoring model of AML using differentially expressed genes to predict prognosis in patients with AML. Furthermore, we evaluated the effectiveness and clinical significance of this prognostic model in 4 AML cohorts and 905 patients with AML. A prognostic risk scoring model of AML containing eight prognosis-related genes was constructed using a multivariate Cox regression model. The model had a higher predictive value for the prognosis of AML in the training and validation sets. In addition, patients with lower scores had significantly better overall survival (OS) and even-free survival (EFS) than those with higher scores among patients with intermediate-risk AML according to the NCCN guidelines, indicating that the model could be used to further predict the prognosis of the intermediate-risk AML populations. Similarly, patients with high scores had remarkably poor OS and EFS in the normal-karyotype populations, indicating that the scoring model had an excellent predictive performance for patients with AML having normal karyotype.ConclusionsOur study provided an individualized prognostic risk score model that could predict the prognosis of patients with AML

Calibration of the Timing Performance of GECAM-C

As a new member of the Gravitational wave high-energy Electromagnetic Counterpart All-sky Monitor (GECAM) after GECAM-A and GECAM-B, GECAM-C (originally called HEBS), which was launched on board the SATech-01 satellite on July 27, 2022, aims to monitor and localize X-ray and gamma-ray transients from $\sim$ 6 keV to 6 MeV. GECAM-C utilizes a similar design to GECAM but operates in a more complex orbital environment. In this work, we utilize the secondary particles simultaneously produced by the cosmic-ray events on orbit and recorded by multiple detectors, to calibrate the relative timing accuracy between all detectors of GECAM-C. We find the result is 0.1 $\mu \rm s$, which is the highest time resolution among all GRB detectors ever flown and very helpful in timing analyses such as minimum variable timescale and spectral lags, as well as in time delay localization. Besides, we calibrate the absolute time accuracy using the one-year Crab pulsar data observed by GECAM-C and Fermi/GBM, as well as GECAM-C and GECAM-B. The results are $2.02\pm 2.26\ \mu \rm s$ and $5.82\pm 3.59\ \mu \rm s$, respectively. Finally, we investigate the spectral lag between the different energy bands of Crab pulsar observed by GECAM and GBM, which is $\sim -0.2\ {\rm \mu s\ keV^{-1}}$.Comment: submitte