Uncovering the Anti-Angiogenic Mechanisms of Centella asiatica via Network Pharmacology and Experimental Validation.

BACKGROUND: Centella asiatica (CA) has been used to address cancer for centuries in traditional Chinese medicine (TCM). Previous studies demonstrated its anti-angiogenesis efficacy, but the underlying mechanism of its action remains to be further clarified. This study aims to investigate the underlying mechanisms of CA and its triterpenes in anti-angiogenesis for cancer therapeutics through network pharmacology and experimental validation. METHODS: Cytoscape was used to construct a network of compound-disease targets and protein-protein interactions (PPIs) from which core targets were identified. GO and KEGG analyses were performed using Metascape, and the AutoDock-Vina program was used to realize molecular docking for further verification. Then, VEGF165 was employed to establish an induced angiogenesis model. The anti-angiogenic effects of CA were evaluated through assays measuring cell proliferation, migration, and tubular structure formation. RESULTS: Twenty-five active ingredients in CA had potential targets for anti-angiogenesis including madecassoside, asiaticoside, madecassic acid, asiatic acid, and asiaticoside B. In total, 138 potential targets for CA were identified, with 19 core targets, including STAT3, SRC, MAPK1, and AKT1. A KEGG analysis showed that CA is implicated in cancer-related pathways, specifically PD-1 and AGE-RAGE. Molecular docking verified that the active components of CA have good binding energy with the first four important targets of angiogenesis. In experimental validation, the extracts and triterpenes of CA improved VEGF165-induced angiogenesis by reducing the proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs). CONCLUSIONS: Our results initially demonstrate the effective components and great anti-angiogenic activity of CA. Evidence of the satisfactory anti-angiogenic action of the extracts and triterpenes from CA was verified, suggesting CA's significant potential as a prospective agent for the therapy of cancer.

Effects of self-help mindfulness-based cognitive therapy on mindfulness, symptom change, and suicidal ideation in patients with depression: a randomized controlled study.

Objective: This study aimed to evaluate the effects of self-help mindfulness-based cognitive therapy (MBCT-SH) on mindfulness, symptom change, and suicidal ideation in patients with depression. Methods: For this randomized controlled study, 97 patients were randomly assigned to either the MBCT-SH (n = 48) or control (n = 49) group. The Five Facet Mindfulness Questionnaire (FFMQ), Hamilton Depression Rating Scale (HAMD-24), and Suicide Attitude Questionnaire (SAQ) were used to assess mindfulness, depression symptoms, and suicidal ideation, respectively, at baseline (T0), intervention week 4 (T1), intervention week 8 (T2), and 3-month follow-up (T3). The groups were also compared on treatment costs and readmission rates at a 6-month follow-up. Results: In the MBCT-SH group, 46 of 48 participants (96%) completed the eight-week program. At T0, there were no statistically significant between-group differences in demographics, clinical characteristics, FFMQ, HAMD-24, or SAQ. Nor were there statistically significant differences on the HAMD-24 or SAQ between the MBCT-SH and control groups at T1 (p = 0.18 and p = 0.59, respectively), while mindfulness was significantly higher in the MBCT-SH group (t = 2.383, p = 0.019). At T2, there were significant between-group differences on the FFMQ, HAMD-24, and SAQ, all of which remained significant at T3. At the 6-month follow-up, per capita treatment costs were 5,298 RMB lower in the MBCT-SH group compared with the control group, while their readmission rates (6.1% and 4.2%, respectively) did not differ significantly. Conclusion: These findings support the feasibility and effectiveness of MBCT-SH among patients with depression. Clinical trial registration: http://www.chictr.org.cn, ChiCTR2300077850.

Genome-Wide Analysis of the RNase T2 Family and Identification of Interacting Proteins of Four ClS-RNase Genes in 'XiangShui' Lemon.

S-RNase plays vital roles in the process of self-incompatibility (SI) in Rutaceae plants. Data have shown that the rejection phenomenon during self-pollination is due to the degradation of pollen tube RNA by S-RNase. The cytoskeleton microfilaments of pollen tubes are destroyed, and other components cannot extend downwards from the stigma and, ultimately, cannot reach the ovary to complete fertilisation. In this study, four S-RNase gene sequences were identified from the 'XiangShui' lemon genome and ubiquitome. Sequence analysis revealed that the conserved RNase T2 domains within S-RNases in 'XiangShui' lemon are the same as those within other species. Expression pattern analysis revealed that S3-RNase and S4-RNase are specifically expressed in the pistils, and spatiotemporal expression analysis showed that the S3-RNase expression levels in the stigmas, styles and ovaries were significantly higher after self-pollination than after cross-pollination. Subcellular localisation analysis showed that the S1-RNase, S2-RNase, S3-RNase and S4-RNase were found to be expressed in the nucleus according to laser confocal microscopy. In addition, yeast two-hybrid (Y2H) assays showed that S3-RNase interacted with F-box, Bifunctional fucokinase/fucose pyrophosphorylase (FKGP), aspartic proteinase A1, RRP46, pectinesterase/pectinesterase inhibitor 51 (PME51), phospholipid:diacylglycerol acyltransferase 1 (PDAT1), gibberellin receptor GID1B, GDT1-like protein 4, putative invertase inhibitor, tRNA ligase, PAP15, PAE8, TIM14-2, PGIP1 and p24beta2. Moreover, S3-RNase interacted with TOPP4. Therefore, S3-RNase may play an important role in the SI of 'XiangShui' lemon.

[Characteristics of Phosphorus Adsorption in Aqueous Solution by Si-modified Peanut Shell Biochar].

In this work, a novel sodium silicate-modified peanut shell biochar(Si-PSB) was synthesized and used as phosphorus adsorbents. Compared with unmodified biochar(PSB), the adsorption capacity of Si-PSBs increased significantly. The adsorption capacity of 8% sodium silicate solution modified biochar(8%Si-PSB) was 3.9 times higher than that of PSB. The biochar was characterized using scanning electron microscopy(SEM), Fourier transformed infrared(FTIR), and X-ray diffraction(XRD), which confirmed that silica was present on the surface of 8%Si-PSB. The introduction of silica improved the reaction activity of biochar's own metal ions by affecting the morphology of calcium carbonate. The 8%Si-PSB had a good adsorption effect on phosphorus in both acid and alkali environments. Phosphorus adsorption by 8%Si-PSB and PSB was described well by the pseudo-second-order model, and the adsorption capacity after equilibrium fluctuated between 2.79 mg·g-1 and 0.71 mg·g-1, respectively. Further, the isothermal adsorption experimental data fitted well to the Langmuir model. The presence of humic acid in the solution inhibited the adsorption of phosphorus by the 8%Si-PSB and PSB. The 8%Si-PSB, as a new low-cost phosphorus removal material, can improve the utilization of metal ions in peanut shell itself.

Molecular targeted and immune checkpoint therapy for advanced hepatocellular carcinoma.

Molecular targeted therapy for advanced hepatocellular carcinoma (HCC) has changed markedly. Although sorafenib was used in clinical practice as the first molecular targeted agent in 2007, the SHARPE and Asian-Pacific trials demonstrated that sorafenib only improved overall survival (OS) by approximately 3 months in patients with advanced HCC compared with placebo. Molecular targeted agents were developed during the 10-year period from 2007 to 2016, but every test of these agents from phase II or phase III clinical trial failed due to a low response rate and high toxicity. In the 2 years after, 2017 through 2018, four successful novel drugs emerged from clinical trials for clinical use. As recommended by updated Barcelona Clinical Liver cancer (BCLC) treatment algorithms, lenvatinib is now feasible as an alternative to sorafenib as a first-line treatment for advanced HCC. Regorafenib, cabozantinib, and ramucirumab are appropriate supplements for sorafenib as second-line treatment for patients with advanced HCC who are resistant, show progression or do not tolerate sorafenib. In addition, with promising outcomes in phase II trials, immune PD-1/PD-L1 checkpoint inhibitors nivolumab and pembrolizumab have been applied for HCC treatment. Despite phase III trials for nivolumab and pembrolizumab, the primary endpoints of improved OS were not statistically significant, immune PD-1/PD-L1 checkpoint therapy remains to be further investigated. This review summarizes the development and progression of molecular targeted and immune-based checkpoint therapies in HCC.

[Nitrogen and Phosphorous Adsorption Characteristics of Suspended Solids Input into a Drinking Water Reservoir via Typhoon Heavy Rainfall].

During typhoon "Mujigae" in October 2015, water samples and surface sediments were collected from Gaozhou Reservoir, a drinking water reservoir, for simulation and analysis of the kinetics of suspended solids adsorption to nitrogen and phosphorus and the adsorption isotherms of suspended solids with different particle sizes and different concentrations. The results showed no obvious nitrogen adsorption of suspended solids of Gaozhou Reservoir. However, the adsorption effect to phosphorus by suspended solids was significant and the equilibrium time of phosphorus adsorption was 10 hours. The adsorption capacity of phosphorus increased with the decrease of sediment particle size when particle sizes were less than 0.25 mm, whereas it increased with the increase of suspended solids concentration when the concentration was in the range of 0.2-2.0 kg·m-3. The adsorption isotherm of suspended solids to phosphorus conformed to the Langmuir and Freundlich models, and the maximum adsorption capacity increased with the decrease of suspended solids particle sizes, which increased with the increase of suspended solids concentrations. The maximum adsorption capacity of suspended solids to phosphorus was 0.073-1.776 mg·g-1. These results indicated that the increase of suspended solids concentration due to the heavy rainfall of the typhoon promoted the adsorption of suspended solids to phosphorus, which reduced eutrophication in Gaozhou Reservoir.

Preparation and properties of multifunctional sinapic acid corn bran arabinoxylan esters.

In the present study, corn bran arabinoxylan (CAX) were modified with sinapic acid (SA) by esterification to generate sinapic acid corn bran arabinoxylan esters (SA-CAX) with various substituted degrees. The structure of SA-CAX was characterized by FT-IR, NMR and UV spectroscopy. And the antioxidant activities of SA-CAX were evaluated by scavenging the 2,2'-diphenyl-1-picrylhydrazyl (DPPH) radical, emulsion lipid oxidation test and the lipid peroxidant level test. Compared with CAX, SA-CAX exhibited superior antioxidant activities in vitro, which indicated that the attachment of SA to CAX could enhance antioxidant activities of CAX. Moreover, the aqueous solution behavior of CAX and SA-CAX was investigated by light scattering, scanning electron microscopy and rheological measurement. The SA-CAX could form the aggregates even at diluted solutions. The hydrophobic association led to a higher viscosity and stronger gel behavior of the SA-CAX aqueous solution than that of CAX aqueous solution.

Effect of two administration routes of Shenmai Injection () on pulmonary gas exchange function after tourniquet-induced ischemia-reperfusion.

OBJECTIVE: To compare the effect between nebulized and intravenous administration of Shenmai Injection () on pulmonary gas exchange function of patients following tourniquet-induced lower limb ischemia-reperfusion. METHODS: Thirty-eight patients scheduled for lower extremity surgery were randomized into three groups using the closed envelop method: Shenmai Injection was administered 30 min before tourniquet inflflation by nebulization [0.6 mL/kg in 10 mL normal saline (NS)] in the nebulization group or by intravenous drip (0.6 mL/kg dissolved in 250 mL of 10% glucose) in the intravenous drip group, and equal volume of NS was given intravenously in the NS group; 15 in each group. Arterial blood gases were analyzed, serum levels of malonaldehyde (MDA) and interleukine-6 (IL-6) and interleukine-8 (IL-8) were determined using the method of thiobarbituric acid reaction and enzyme-linked immuno sorbent assay respectively just before tourniquet inflflation (T0), and at 0.5 h (T1), 2 h (T2), 6 h (T3) after tourniquet deflflation. RESULTS: Compared with baselines at T0, MDA levels signifificantly increased at T2, T3 in the NS group and at T3 in the nebulization group, and IL-6 and IL-8 levels were signifificantly increased at T2, T3 in NS, the intravenous drip and the nebulization groups (P <0.05). Arterial pressure of oxygen (PaO2) at T3 was decreased, while alveolararterial oxygen tension showed difference (PA-aDO2) at T3 in the NS group; RI at T3 in both intravenous drip and the nebulization groups were enhanced (P <0.05). Compared with the NS group, MDA and IL-8 levels at T2, T3, IL-6 at T3 in the intravenous drip group, and IL-8 at T3 in the nebulization group were all remarkably increased (P <0.05). Additionally, MDA level at T3 in the nebulization group was higher than that in the intravenous drip group (P <0.05). CONCLUSIONS: Intravenous administration of Shenmai Injection provided a better protective effect than nebulization in mitigating pulmonary gas exchange dysfunction in patients following tourniquet-induced limb ischemia-reperfusion.

Effects on functional groups and zeta potential of SAP1<MW<3kDa treated by pulsed electric field technology.

BACKGROUND: SAP1

[Eutrophication and Characteristics of Cyanobacteria Bloom in the Summer in Guishi Reservoir].

Large-scale cyanobacteria bloom occurred in the summer of 2014 in the Guishi Reservoir that is an important drinking water source for Hezhou City. The dynamic change regularity, external pollution sources, and the phytoplankton community characteristics during the bloom were investigated to evaluate the eutrophication in the reservoir and to present effective prevention and control measures. The results showed that nitrogen and phosphorus concentrations increased year by year; water quality on some sites has been out of class Ⅱ of national water quality standards; and the main pollution source was the agricultural non-point sources. Phytoplankton cell density was in the range of 8.60×106-5.36×108 cells·L-1 and chlorophyll a concentrations reached 74.48 µg·L-1 during the bloom. The dominant species was Microcystis wesenbergii whose density reached 5.36×108 cells·L-1. The cell density decreased over time and concentrated on the surface and at the depth of 2 m underwater. The total phytoplankton cell density was strongly correlated to total phosphorus, total nitrogen, nitrate nitrogen, and the permanganate index, and was inversely correlated to transparency. The water in the Guishi Reservoir was not polluted by microcystic toxins. Moreover, Guishi Reservoir is in a meso-eutrophic state; therefore, the prevention and control of the cyanobacteria bloom should focus on weather conditions and on reducing the input of nitrogen and phosphorus to keep the nutrient levels low.

Mechanism of Bushen Jianpi decoction in preventing and treating osteoporosis caused by aromatase inhibitors in breast cancer treatment.

PURPOSE: Research on the mechanism of Bushen Jianpi decoction (BJD) for preventing and treating osteoporosis caused by aromatase inhibitors (AI) during treatment for breast cancer resection. METHODS: An ovariectomized mouse model was established using random division into 6 groups: a sham ovariectomized group, a blank control group, a control group, an alendronate group, a BJD group, and a drug combination group. Mice breast cancer cell lines (4T1) were cultured and seeded into the armpits of 6 groups of BALB/c mice. The mouse breast cancer postoperative model was built when resecting the tumor after 3 weeks following seeding tumor. After 1 weeks, the 6 groups of mice were given different drugs. Then the following analyses were made: estradiol (E2) levels and alkaline phosphatase (ALP) levels in the serum; detection of in vitro bone density and calcium and bone phosphorus content; tumor pathology and immunohistochemistry detection. RESULTS: The results suggested that BJD decreased levels of ALP in ovariectomized mice, and there was a trend for improved bone loss. BJD strengthened the trend of alendronate to improve bone loss, improved bone density, bone calcium and phosphorous, and reduced ALP. BJD had a certain role on the promotion of the expression of estrogen receptors (ERs) in the relapse of the tumor tissue. CONCLUSIONS: Combined therapy with BJD and alendronate can act synergistically against osteoporosis, which was possibly related to a reduced bone conversion rate through inhibiting bone resorption. BJD may block the MAPK signal pathway in breast cancer cells, increasing the expression of ERs and making cancer cells sensitive to endocrine treatment.

Effect of two administration routes of Shenmai Injection () on pulmonary gas exchange function after tourniquet-induced ischemia-reperfusion / 中国结合医学杂志

<p><b>OBJECTIVE</b>To compare the effect between nebulized and intravenous administration of Shenmai Injection () on pulmonary gas exchange function of patients following tourniquet-induced lower limb ischemia-reperfusion.</p><p><b>METHODS</b>Thirty-eight patients scheduled for lower extremity surgery were randomized into three groups using the closed envelop method: Shenmai Injection was administered 30 min before tourniquet inflflation by nebulization [0.6 mL/kg in 10 mL normal saline (NS)] in the nebulization group or by intravenous drip (0.6 mL/kg dissolved in 250 mL of 10% glucose) in the intravenous drip group, and equal volume of NS was given intravenously in the NS group; 15 in each group. Arterial blood gases were analyzed, serum levels of malonaldehyde (MDA) and interleukine-6 (IL-6) and interleukine-8 (IL-8) were determined using the method of thiobarbituric acid reaction and enzyme-linked immuno sorbent assay respectively just before tourniquet inflflation (T0), and at 0.5 h (T1), 2 h (T2), 6 h (T3) after tourniquet deflflation.</p><p><b>RESULTS</b>Compared with baselines at T0, MDA levels signifificantly increased at T2, T3 in the NS group and at T3 in the nebulization group, and IL-6 and IL-8 levels were signifificantly increased at T2, T3 in NS, the intravenous drip and the nebulization groups (P <0.05). Arterial pressure of oxygen (PaO) at T3 was decreased, while alveolararterial oxygen tension showed difference (PA-aDO) at T3 in the NS group; RI at T3 in both intravenous drip and the nebulization groups were enhanced (P <0.05). Compared with the NS group, MDA and IL-8 levels at T2, T3, IL-6 at T3 in the intravenous drip group, and IL-8 at T3 in the nebulization group were all remarkably increased (P <0.05). Additionally, MDA level at T3 in the nebulization group was higher than that in the intravenous drip group (P <0.05).</p><p><b>CONCLUSIONS</b>Intravenous administration of Shenmai Injection provided a better protective effect than nebulization in mitigating pulmonary gas exchange dysfunction in patients following tourniquet-induced limb ischemia-reperfusion.</p>

Heterogeneity of Human Neutrophil CD177 Expression Results from CD177P1 Pseudogene Conversion.

Most humans harbor both CD177neg and CD177pos neutrophils but 1-10% of people are CD177null, placing them at risk for formation of anti-neutrophil antibodies that can cause transfusion-related acute lung injury and neonatal alloimmune neutropenia. By deep sequencing the CD177 locus, we catalogued CD177 single nucleotide variants and identified a novel stop codon in CD177null individuals arising from a single base substitution in exon 7. This is not a mutation in CD177 itself, rather the CD177null phenotype arises when exon 7 of CD177 is supplied entirely by the CD177 pseudogene (CD177P1), which appears to have resulted from allelic gene conversion. In CD177 expressing individuals the CD177 locus contains both CD177P1 and CD177 sequences. The proportion of CD177hi neutrophils in the blood is a heritable trait. Abundance of CD177hi neutrophils correlates with homozygosity for CD177 reference allele, while heterozygosity for ectopic CD177P1 gene conversion correlates with increased CD177neg neutrophils, in which both CD177P1 partially incorporated allele and paired intact CD177 allele are transcribed. Human neutrophil heterogeneity for CD177 expression arises by ectopic allelic conversion. Resolution of the genetic basis of CD177null phenotype identifies a method for screening for individuals at risk of CD177 isoimmunisation.

Cross-linking of interfacial casein layer with genipin prevented pH-induced structural instability and lipase digestibility of the fat droplets.

The present study provided a new approach to enhance the stability of protein-emulsified nanoemulsions and to control the lipase digestibility of lipid droplets through spontaneous cross-linking of the interfacial layer with genipin, a functional ingredient isolated from the fruit of Gardenia jasminoides E. Cross-linking casein-emulsified nanoemulsions under different genipin/casein mass ratios (1:20, 1:10, 1:5) significantly (p < 0.05) or very significantly (p < 0.01) enhanced their stability under harsh gastric pH environments and prevented nanoemulsion flocculation. As observed by transmission electron microscope (TEM), under the pH 1.2 condition, the genipin cross-linked nanoemulsion showed more compact microstructure with clear and defined contour as well as "core-shell" structure caused by the swelling of the surface protein film. Interestingly, the intestinal digestibility of lipid droplets was delayed very significantly (p < 0.01) after cross-linking the interfacial casein layer with genipin, which was enhanced by the increase in genipin/casein mass ratio and cross-linking time.

The effect of high moisture heat-acid treatment on the structure and digestion property of normal maize starch.

The objective of this study was to analyze the influence of thermal-acid treatment on the formation of resistant starch (RS). The maximum RS content in citric acid-heat treated starches (CAHT) reached 36.55%, which was 7 times higher of that in native starch. According to HPSEC-MALLS-RI analysis, amylopectin was more susceptible to hydrolysis than amylose during citric acid-heat treatment (CAH). X-ray measurement revealed that even though the starch crystalline pattern was changed from A-type to a more resistant B-type after CAH, the fraction of crystalline region decreased from 21.16% to 8.37%. The hydroxyls on the starch chains were substituted by the citric acid anhydrides during CAH according to FT-IR analysis, which led to the formation of ester bond cross-linking structures in starch granules, and it could be the main contribution to the increase of RS content in CAHT samples.

Combination of oxaliplatin and S-1 versus sorafenib alone in patients with advanced hepatocellular carcinoma.

Sorafenib and conventional systemic cytotoxicity chemotherapy are currently being used in parallel for the patients with advanced hepatocellular carcinoma (HCC). While sorafenib has been proven to improve the prognosis in patients with this malignant disease, however, the outcome of other newly developed systemic chemotherapeutic regimens remains controversial. We evaluated the outcome and safety of patients treated with the SOX regimen (oxaliplatin + S-1) and those treated with sorafenib in a single-center cohort. This retrospective study involved a total of 46 patients with advanced HCC, 22 of which were treated with SOX regimen (oxaliplatin [130 mg/m2] on day 1 and S-1 [80 mg/m2/day] on day 1-14, every 3 weeks), and 24 were daily treated with sorafenib (400 mg, b.i.d.). The median progression-free survival was 3.6 months (95% confidence interval [CI], 1.7 to 5.6) with SOX and 1.7 months (95% CI, 1.5 to 1.9) with sorafenib, respectively (P = 0.444). The median overall survival in SOX and sorafenib group was 7.6 months (95% CI, 4.3 to 10.9) and 4.7 months (95% CI, 2.7 to 7.3), respectively (P = 0.246). Response rate was 22.2% with SOX and 5.6% with sorafenib, respectively (P = 0.154). The frequent side effects in SOX-treated patients were thrombocytopenia, elevation of transaminase levels and neuropathy, whereas hand-foot syndrome, diarrhea and pruritus were common in sorafenib-treated patients. These preliminary results suggest that the SOX regimen may serve as an effective treatment for patients with advanced HCC, and the treatment-related toxicities were generally well-tolerated.

Baicalein induces apoptosis via a mitochondrial-dependent caspase activation pathway in T24 bladder cancer cells.

Recurrence of bladder cancer following transurethral resection of bladder tumor (TURBt) is an obstacle in clinical management. In the current study, we investigated the antitumor activity of baicalein, a Chinese herbal medicine, against T24 bladder cancer cells in vitro. Baicalein inhibited growth and caused G1/S arrest of the cell cycle in the T24 cells. Moreover, baicalein induced apoptosis via loss of mitochondrial transmembrane potential (ΔΨm), release of cytochrome c and activation of caspase-9 and caspase-3. Baicalein inhibited Akt phosphorylation, downregulated Bcl-2 expression and upregulated Bax expression, which in turn increased the ratio of Bax/Bcl-2. Our results demonstrate that baicalein repressed growth inhibition and induced apoptosis via loss of ΔΨm and activation of caspase-9 and caspase-3 in T24 bladder cancer cells, which indicates that baicalein may be an effective agent in the clinical management of bladder cancer.

Physical and antimicrobial properties of peppermint oil nanoemulsions.

The mixture of peppermint oil (PO) with medium-chain triacylglycerol was emulsified in water and stabilized with a food-grade biopolymer, modified starch, to form PO nanoemulsions. The effects of emulsifying conditions including homogenization pressure, the number of processing cycles, and oil loading on the mean diameters and viscosities of nanoemulsions were characterized by dynamic light scattering, optical microscopy, and rheological measurements. The formulated PO nanoemulsions with mean diameters normally <200 nm showed high stability over at least 30 days of storage time. Their antimicrobial properties related to those of PO have also been evaluated by two assays, the minimum inhibitory concentration (MIC) and time-kill dynamic processes, against two Gram-positive bacterial strains of Listeria monocytogenes Scott A and Staphylococcus aureus ATCC 25923. Compared with bulk PO, the PO nanoemulsions showed prolonged antibacterial activities. The results suggest that the nanoemulsion technology can provide novel applications of essential oils in extending the shelf life of aqueous food products.

Preferential inhibition of hepatocellular carcinoma by the flavonoid Baicalein through blocking MEK-ERK signaling.

Baicalein is a purified flavonoid extracted from the roots of Scutellaria baicalensis or Scutellaria radix. Although previous studies have suggested that Baicalein possesses an in vitro anti-hepatocellular carcinoma activity, its in vivo effects and mechanisms of action are still not completely understood. In this study, Baicalein at concentrations of 40-120 µM exhibited significant cytotoxicity to three hepatocellular carcinoma (HCC) cell lines but marginal cytotoxicity to a normal liver cell line in vitro. Compared to a standard chemotherapy drug, 5-fluorouracil (5-FU), Baicalein had greater effect on HCC cells but less toxicity on normal liver cells. Treatment with Baicalein dramatically reduced mitochondrial transmembrane potential, and activated caspase-9 and caspase-3. Blockade of Baicalein-induced apoptosis with a pan-caspase inhibitor partially attenuated Baicalein-induced growth inhibition in HCC. Baicalein treatment significantly inhibited tumor growth of HCC xenografts in mice. Induction of apoptosis was demonstrated in Baicalein-treated xenograft tumors by the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Furthermore, Baicalein treatment dramatically decreased the levels of phosphorylation of MEK1, ERK1/2 and Bad in vitro and in vivo. Overexpression of human MEK1 partially blocked Baicalein-induced growth inhibition. Consequently, these findings suggest that Baicalein preferentially inhibits HCC tumor growth through inhibition of MEK-ERK signaling and by inducing intrinsic apoptosis.

[Studies on the chemical constituents of Rubus parvifolius].

OBJECTIVE: To study the chemical constituents of Rubus parvifoliu. METHODS: The constituents were isolated by column chromatography and their structures were elucidated through spectroscopic analysis such as 1H-NMR, 13C-NMR, FT-IR, et al. RESULTS: Seven compounds were isolated from the roots of Rubus parvifolius L., they were identified as p-sitosterol (I), lauric acid (II), O-nitrophenol (III), beta-daucosterol (IV), euscaphic acid (V), camelliagenin A (VI) and(+) -catech in (VII). CONCLUSION: Compounds III and VII are isolated from the plant for the first time.