Mechanism of hepatic stellate cell proliferation and apoptosis in rats by promoting circulation, removing stasis, and dredging collaterals based on the theory of liver collateral disease.

BACKGROUND: This study aims to investigate the impacts on the proliferation, inhibition, apoptosis, and cell cycle of hepatic stellate cells (HSC-T6) in rats by using traditional Chinese medicine (TCM) in serum. METHODS: Twenty-seven rats were randomly divided into nine groups on average: a blank control (BC) group (fed by distilled water), a positive control group (colchicine solution, 0.05 mg/mL), and seven TCM groups [with the aim of clearing the liver of choleresis with 0.24 g/mL (weight of TCM herbs per milliliter), 0.73 g/mL, 1.22 g/mL, 2.45 g/mL, 7.34 g/mL, 12.24 g/mL, 24.48 g/mL]. Each rat received gavage with a dose of 1 mL/100 g twice a day for 7 days to prepare the drug serum. The HSC-T6 were divided into a TCM serum group, a positive control group, and a BC group. The TCM group and the positive control group were given corresponding drug serum for incubation, while the BC group received the medium without drug serum. RESULTS: The cellular proliferation inhibition rate in the positive control and TCM groups was significantly higher (P<0.01) than that in the BC group. The number of cells in the positive, 0.24 g/mL TCM, 1.22 g/mL TCM, and 7.34 g/mL TCM groups increased significantly (P<0.05) in the G0/G1 phase compared with the BC group. The number of cells in the positive group and all the TCM groups clearly increased in phase S by 0.73 g/mL in the TCM group, 2.45 g/mL in the TCM group, 12.24 g/mL in the TCM group, and 24.48 g/mL in the TCM group compared with the BC group, and the difference was statistically significant (P<0.05). The number of cells in the G2/M phase of the positive control group and all the TCM groups decreased significantly. Compared with the BC group, the positive group, 0.24 g/mL TCM group, 0.73 g/mL TCM group, 1.22 g/mL TCM group, 2.45 g/mL TCM group have statistically difference (P<0.05). CONCLUSIONS: A Qinggan Lidan prescription may exert anti-hepatic fibrosis effects by blocking HSC-T6 in the G0/G1 and S phases and by suppressing the proliferation of HSC-T6.

Genomic insights into the formation of human populations in East Asia.

The deep population history of East Asia remains poorly understood owing to a lack of ancient DNA data and sparse sampling of present-day people1,2. Here we report genome-wide data from 166 East Asian individuals dating to between 6000 BC and AD 1000 and 46 present-day groups. Hunter-gatherers from Japan, the Amur River Basin, and people of Neolithic and Iron Age Taiwan and the Tibetan Plateau are linked by a deeply splitting lineage that probably reflects a coastal migration during the Late Pleistocene epoch. We also follow expansions during the subsequent Holocene epoch from four regions. First, hunter-gatherers from Mongolia and the Amur River Basin have ancestry shared by individuals who speak Mongolic and Tungusic languages, but do not carry ancestry characteristic of farmers from the West Liao River region (around 3000 BC), which contradicts theories that the expansion of these farmers spread the Mongolic and Tungusic proto-languages. Second, farmers from the Yellow River Basin (around 3000 BC) probably spread Sino-Tibetan languages, as their ancestry dispersed both to Tibet-where it forms approximately 84% of the gene pool in some groups-and to the Central Plain, where it has contributed around 59-84% to modern Han Chinese groups. Third, people from Taiwan from around 1300 BC to AD 800 derived approximately 75% of their ancestry from a lineage that is widespread in modern individuals who speak Austronesian, Tai-Kadai and Austroasiatic languages, and that we hypothesize derives from farmers of the Yangtze River Valley. Ancient people from Taiwan also derived about 25% of their ancestry from a northern lineage that is related to, but different from, farmers of the Yellow River Basin, which suggests an additional north-to-south expansion. Fourth, ancestry from Yamnaya Steppe pastoralists arrived in western Mongolia after around 3000 BC but was displaced by previously established lineages even while it persisted in western China, as would be expected if this ancestry was associated with the spread of proto-Tocharian Indo-European languages. Two later gene flows affected western Mongolia: migrants after around 2000 BC with Yamnaya and European farmer ancestry, and episodic influences of later groups with ancestry from Turan.

[Dynamic Changes of Ultrasonographic Images of Zusanli (ST 36) Region During Deqi of Acupuncture Needle Stimulation].

OBJECTIVE: To observe the dynamic changes of ultrosonographic images of Zusanli (ST 36) area during Deqi after inserting acupuncture needles, so as to provide objective evidence for clinical Deqi. METHODS: Sixty healthy volunteers (30 men and 30 women) were recruited in the present study. The subjects were asked to take a supine position on a test-bed, sterilized disposable filiform needles were perpendicularly inserted into bilateral ST 36 till Deqi (without lifting, thrusting and twirling), when, high-resolution ultrasound scanning was conducted over the regional skeletal muscles by using a radio-frequency (5-12 MHz) coil probe (Philips IU Elite Ultrasound Diagnostic Instrument) after smearing a layer of gel at the skin of ST 36. RESULTS: Among these 120 points of the 60 volunteer subjects, a marked Deqi was obtained from 108 points (consisting of 90%) including 52 points in men and 56 in women, and 53 at the left ST 36 and 56 at the right ST 36. Ultrosonographic scanning displayed that when a strongest Deqi feeling was obtained from bilateral ST 36 in these 60 volunteers, the acupuncture needle-tip was about (25.32±5.82) mm in the vertical depth, and was (5.45±0.55) mm lateral to the tibia, involving the anterior tibial muscle near the deep fascia in 46 acupoints, and the intersection fascia of anterior tibial muscle and extensor digitorum longus in 62 acupoints. CONCLUSIONS: The anterior tibial muscle near the deep fascia and the intersection fascia of anterior tibial muscle and extensor digitorum longus around ST 36 are involved in strongest Deqi. There are no significant differences in the gender and location (left and right).

Transcriptome profiling analysis reveals the role of silique in controlling seed oil content in Brassica napus.

Seed oil content is an important agronomic trait in oilseed rape. However, the molecular mechanism of oil accumulation in rapeseeds is unclear so far. In this report, RNA sequencing technique (RNA-Seq) was performed to explore differentially expressed genes in siliques of two Brassica napus lines (HFA and LFA which contain high and low oil contents in seeds, respectively) at 15 and 25 days after pollination (DAP). The RNA-Seq results showed that 65746 and 66033 genes were detected in siliques of low oil content line at 15 and 25 DAP, and 65236 and 65211 genes were detected in siliques of high oil content line at 15 and 25 DAP, respectively. By comparative analysis, the differentially expressed genes (DEGs) were identified in siliques of these lines. The DEGs were involved in multiple pathways, including metabolic pathways, biosynthesis of secondary metabolic, photosynthesis, pyruvate metabolism, fatty metabolism, glycophospholipid metabolism, and DNA binding. Also, DEGs were related to photosynthesis, starch and sugar metabolism, pyruvate metabolism, and lipid metabolism at different developmental stage, resulting in the differential oil accumulation in seeds. Furthermore, RNA-Seq and qRT-PCR data revealed that some transcription factors positively regulate seed oil content. Thus, our data provide the valuable information for further exploring the molecular mechanism of lipid biosynthesis and oil accumulation in B. nupus.

Tongxinluo Inhibits Renal Fibrosis in Diabetic Nephropathy: Involvement of the Suppression of Intercellular Transfer of TGF-[Formula: see text]1-Containing Exosomes from GECs to GMCs.

Glomerular mesangial cells (GMCs) activation is implicated in the pathogenesis of diabetic nephropathy (DN). Our previous study revealed that high glucose (HG)-treated glomerular endothelial cells (GECs) produce an increased number of TGF-[Formula: see text]1-containing exosomes to activate GMCs through the TGF-[Formula: see text]1/Smad3 signaling pathway. We also identified that Tongxinluo (TXL), a traditional Chinese medicine, has beneficial effects on the treatment of DN in DN patients and type 2 diabetic mice. However, it remained elusive whether TXL could ameliorate renal structure and function through suppression of intercellular transfer of TGF-[Formula: see text]1-containing exosomes from GECs to GMCs. In this study, we demonstrate that TXL can inhibit the secretion of TGF-[Formula: see text]1-containing exosomes from HG-treated GECs. Furthermore, exosomes produced by HG induced-GECs treated with TXL cannot trigger GMC activation, proliferation and extracellular matrix (ECM) overproduction both in vitro and in vivo. These results suggest that TXL can prevent the transfer of TGF-[Formula: see text]1 from GECs to GMCs via exosomes, which may be one of the mechanisms of TXL in the treatment of DN.

Current natural products with antihypertensive activity.

Natural products have been an important source of new drugs, which also played a dominant role in the discovery and research of new drugs for the treatment of hypertension. This review article reviews the recent progress in the research and development of natural lead compounds with antihypertensive activity, including alkaloids, diterpenes, coumarins, flavonoids, and peptides. We summarized their structures, sources, as well as the antihypertensive mechanisms. These information provides instructive reference for the following structural modifications and optimization.

Synthesis of 13-ß-elemene ester derivatives and evaluation of their antioxidant activity in human umbilical vein endothelial cells.

In the present study, a series of 13-ß-elemene ester derivatives were designed and prepared, and their antioxidant activity was investigated in the H2O2-treated human umbilical vein endothelial cells (HUVECs). Among the test compounds, the dimer compounds 5v and 5w exhibited the most potent antioxidant activity with significant ROS suppression being observed. Both compounds markedly inhibited the H2O2-induced changes in various biochemical substances, such as superoxide dismutase (SOD), malonyldialdehyde (MDA), nitric oxide (NO), and lactic dehydrogenase (LDH), which were superior to that of the positive control vitamin E. Further more, they did not produce any obvious cytotoxicity, but increased the viability of HUVECs injured by H2O2 in a dose-dependent manner. Additionally, compound 5w, designed as a prodrug-like compound, showed improved stability relative to compound 4 in vitro.

Total synthesis of neokotalanol, a potent α-glucosidase inhibitor isolated from Salacia reticulata.

Neokotalanol, a potent α-glucosidase inhibitor isolated from Salacia reticulata, was synthesized through a key coupling reaction between a perbenzylated thiosugar and an appropriately protected perseitol triflate derived from D-mannose. This key step was found to be quite temperature dependent, and a simultaneous cyclization of the triflate leading to a characteristic 2,4,7-trioxabicyclo[4.2.1]nonane system was detected.

Synthesis and ß-adrenergic blocking activity of oxime ether hybrids derived from a natural isochroman-4-one.

AIM: In a search for new cardiovascular drug candidates, a series of novel oxime ethers derived from a natural isochroman-4-one were synthesized. METHOD: Compounds 3 and 6, derived from the natural antihypertensive compound 7, 8-dihydroxy-3-methyl-isochroman-4-one (XJP), were designed and synthesized. Subsequently, a series of novel isochroman-4-one oxime ether hybrids were prepared by hybridizing various N-substituted isopropanolamine functionalities to isochroman-4-one oxime. Furthermore, ß1-adrenergic blocking activities of the synthesized compounds were assayed using the isolated rat left atria. RESULTS: Twenty target compounds were obtained, and the preliminary structure-activity relationships were deduced. The most promising compound Ic exhibited ß1-adrenoceptor blocking activity (inhibition: 52.2%) at 10(-7) mol·L(-1), which was superior to that of propranolol (inhibition: 49.7%). CONCLUSION: The results suggested that natural product XJP/isopropanolamine moiety hybrids may provide a promising approach for the discovery of novel cardiovascular drug candidates.

Glycosylation of ent-kaurene derivatives and an evaluation of their cytotoxic activities.

AIM: To discover more active and water-soluble derivatives of tetracyclic diterpenoids containing an exo-methylene cyclopentanone or an α-methylenelactone moiety. METHODS: All of the key intermediates were synthesized from stevioside, and the target compounds were obtained through glycosylation of the 4-carboxyl group. The cytotoxicity of the target compounds against six human cancer cell lines, HepG2, Bel-7402, A549, U251, MCF-7 and MDA-MB-231, were evaluated by the MTT assay. RESULTS: Compound 1b was more effective than the positive control adriamycin against the HepG2, Bel-7402, A549, MCF-7, and MDA-MB-231 cell lines with IC50 values of 0.12, 0.91, 0.35, 0.08, and 0.07 µmol·L(-1), respectively. Moreover, compound 3c exhibited the most potent and selective cytotoxic activity against the HepG2 cell line (IC50, 0.01 µmol·L(-1)). CONCLUSION: Compounds 1b and 3c could be considered as potential anticancer candidates for further study.

[Progress in small-molecule inhibitors of Bcl-2 family proteins].

Apoptosis is an essential factor in keeping homeostasis of the organism. Apoptosis is regulated by a series of cytokines. Bcl-2 family proteins are key regulators of apoptosis. The Bcl-2 family includes both anti- and pro-apoptotic proteins with opposing biological functions. Their interaction regulates the transmission of the apoptosis signal. High expression of anti-apoptotic members such as Bcl-2 and Bcl-xL are commonly found in human cancers. In recent years, following the disclosing of the crystal structures of Bcl-2 family proteins, researchers have paid attention to the development of the small molecule inhibitors of Bcl-2 family proteins. This article reviews the progress in this field from the view of drug design.

Quantitative determination of oil content in small quantity of oilseed rape by ultrasound-assisted extraction combined with gas chromatography.

Accurately quantitative determination of oil content in oilseed rape plays an important role in varieties breeding for improving oil content in seeds. However, large quantity of oilseeds were needed in order to obtain accuracy and precision results by using standard Soxhlet extraction method, which may be a handicap in analysis of small, rare and precious samples in plant breeding. In the present work, ultrasound-assisted extraction was evaluated as a simpler and more effective alternative to conventional extraction method for the isolation of oil from small quantity of oilseed rape (<20 mg). The oil of oilseed rape samples was extracted by ultrasound-assisted method, and then the fatty acids and total oil content of the seeds were qualitatively and quantitatively determined by gas chromatography (GC). Extraction efficiency of total oil obtained by ultrasound-assisted extraction through an orthogonal experiment (L(9) (3(4))) were investigated to get the best extraction conditions. Statistical analysis showed that the variable with the largest effect was the ultrasound-assisted extraction time which was followed by the ultrasound-assisted extraction power, and the liquid:solid ratio. A liquid:solid ratio of 1:4 (L:g), an ultrasound-assisted extraction time of 60 min and an ultrasound-assisted extraction power of 500 W were found to be optimal for oil extraction from oilseed rape. By comparing with the conventional method, it was found that the ultrasound-assisted extraction of oil from oilseed rape was about five times faster than the traditional extraction method. By the use of ultrasound-assisted extraction combined with GC analysis, the fatty acids and total oil content in small quantity of seeds (<20 mg) were successfully qualitatively determined and the results are in agreement with that obtained by traditional standard method.

[Chemical constituents of the aerial parts of Rhamnus crenatus].

AIM: To study chemical constituents of the aerial parts of Rhamnus crenatus sieb. et zucc. METHODS: The chemical constituents were isolated by chromatographic methods and their structures were elucidated on the basis of spectral analysis. RESULTS: Five compounds were isolated and their structures were identified as crenatoside (1), torachrysone (2), emodin (3), emodin-1-O-beta-D-glucopyranoside (4) and beta-sitosterol (5) respectively. CONCLUSION: Compound 1 is a new compound and the others were isolated from Rhamnus crenatus for the first time.