Research Progress on the Effect of Nitrogen on Rapeseed between Seed Yield and Oil Content and Its Regulation Mechanism.

Rapeseed (Brassica napus L.) is one of the most important oil crops in China. Improving the oil production of rapeseed is an important way to ensure the safety of edible oil in China. Oil production is an important index that reflects the quality of rapeseed and is determined by the oil content and yield. Applying nitrogen is an important way to ensure a strong and stable yield. However, the seed oil content has been shown to be reduced in most rapeseed varieties after nitrogen application. Thus, it is critical to screen elite germplasm resources with stable or improved oil content under high levels of nitrogen, and to investigate the molecular mechanisms of the regulation by nitrogen of oil accumulation. However, few studies on these aspects have been published. In this review, we analyze the effect of nitrogen on the growth and development of rapeseed, including photosynthetic assimilation, substance distribution, and the synthesis of lipids and proteins. In this process, the expression levels of genes related to nitrogen absorption, assimilation, and transport changed after nitrogen application, which enhanced the ability of carbon and nitrogen assimilation and increased biomass, thus leading to a higher yield. After a crop enters the reproductive growth phase, photosynthates in the body are transported to the developing seed for protein and lipid synthesis. However, protein synthesis precedes lipid synthesis, and a large number of photosynthates are consumed during protein synthesis, which weakens lipid synthesis. Moreover, we suggest several research directions, especially for exploring genes involved in lipid and protein accumulation under nitrogen regulation. In this study, we summarize the effects of nitrogen at both the physiological and molecular levels, aiming to reveal the mechanisms of nitrogen regulation in oil accumulation and, thereby, provide a theoretical basis for breeding varieties with a high oil content.

Research Progress in High-Efficiency Utilization of Nitrogen in Rapeseed.

Nitrogen (N) is one of the most important mineral elements for plant growth and development and a key factor for improving crop yield. Rapeseed, Brassica napus, is the largest oil crop in China, producing more than 50% of the domestic vegetable oil. However, high N fertilizer input with low utilization efficiency not only increases the production cost but also causes serious environmental pollution. Therefore, the breeding of rapeseed with high N efficiency is of great strategic significance to ensure the security of grain and oil and the sustainable development of the rapeseed industry. In order to provide reference for genetic improvement of rapeseed N-efficient utilization, in this article, we mainly reviewed the recent research progress of rapeseed N efficiency, including rapeseed N efficiency evaluation, N-efficient germplasm screening, and N-efficient physiological and molecular genetic mechanisms.

Calunduloside E inhibits HepG2 cell proliferation and migration via p38/JNK-HMGB1 signalling axis.

High-mobility group box 1 (HMGB1), a highly conserved chromosome protein, is considered as a potential therapeutic target and novel biomarker because of its regulation in the proliferation and metastasis of Hepatocellular carcinoma (HCC). Calenduloside E (CE), a natural active product, has been reported to anti-cancer effect. However, the role and underlying molecular mechanism of CE in HCC is still unclear. The purpose of this study is to investigate the effects of CE on the proliferation and migration of HCC, and then explore the possible underlying molecular mechanism. HepG2 cells were treated with CE or transfected with HMGB1 shRNA plasmids, EdU and colony formation assays were used to detect cell proliferation ability. Wound healing and transwell assays were used to determine the role of CE in cell migration. The expression of Cyclins, PCNA, MMPs, HMGB1, N-cadherin, E-cadherin and phosphorylation of p38, ERK and JNK were all detected using Western blotting. Our results showed that CE inhibited HepG2 cells proliferation and migration in a dose dependent manner; reduced the expression levels of Cycins, PCNA, HMGB1, MMPs and N-cadherin; up-regulated E-cadherin expression; enhanced the phosphorylation of p38 and JNK signalling pathways. Blocking the activation of p38 and JNK obviously reversed CE-mediated inhibitory effects on HepG2 cell proliferation and migration; reversed CE-induced down-regulation of Cyclins, PCNA, MMPs, N-cadherin and HMGB1, as well as E-cadherin up-regulation. In conclusion, our study suggested that CE reduces the expression levels of Cyclins, MMPs and epithelial-mesenchymal transformation (EMT) through p38/JNK-HMGB1 signaling axis and then inhibits HepG2 cells proliferation and migration in HepG2 cells. This study provides a new perspective for the anti-tumour molecular mechanism of CE in HCC.

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.

Complete chloroplast genome features and phylogenetic analysis of Eruca sativa (Brassicaceae).

Eruca sativa Mill. (Brassicaceae) is an important edible vegetable and a potential medicinal plant due to the antibacterial activity of its seed oil. Here, the complete chloroplast (cp) genome of E. sativa was de novo assembled with a combination of long PacBio reads and short Illumina reads. The E. sativa cp genome had a quadripartite structure that was 153,522 bp in size, consisting of one large single-copy region of 83,320 bp and one small single-copy region of 17,786 bp which were separated by two inverted repeat (IRa and IRb) regions of 26,208 bp. This complete cp genome harbored 113 unique genes: 79 protein-coding genes, 30 tRNA genes, and four rRNA genes. Forty-nine long repetitive sequences and 69 simple sequence repeats were identified in the E. sativa cp genome. A codon usage analysis of the E. sativa cp genome showed a bias toward codons ending in A/T. The E. sativa cp genome was similar in size, gene composition, and linearity of the structural region when compared with other Brassicaceae cp genomes. Moreover, the analysis of the synonymous (Ks) and non-synonymous (Ka) substitution rates demonstrated that protein-coding genes generally underwent purifying selection pressure, expect ycf1, ycf2, and rps12. A phylogenetic analysis determined that E. sativa is evolutionarily close to important Brassica species, indicating that it may be possible to transfer favorable E. sativa alleles into other Brassica species. Our results will be helpful to advance genetic improvement and breeding of E. sativa, and will provide valuable information for utilizing E. sativa as an important resource to improve other Brassica species.

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.

Safety and Efficacy Evaluation of Traditional Chinese Medicine (Qingre-Lishi-Yishen Formula) Based on Treatment of Regular Glucocorticoid Combined with Cyclophosphamide Pulse in Children Suffered from Moderately Severe Henoch-Schonlein Purpura Nephritis with Nephrotic Proteinuria.

OBJECTIVE: At present, the most appropriate management of Henoch-Schonlein purpura nephritis (HSPN) with nephrotic-range proteinuria still remains controversial; thus, the purpose of this study is to evaluate safety and efficacy of traditional Chinese medicine (TCM), Qingre-Lishi-Yishen Formula (QLYF), integrated with regular oral glucocorticoid and cyclophosphamide intravenous pulse therapeutic regimen in children suffered from moderately severe HSPN with nephrotic proteinuria. METHODS: From 1 January 2012, to 1 January 2016, totally 150 hospitalized children suffered from HSPN with nephrotic proteinuria were included. All were treated with glucocorticoid and cyclophosphamide, and 100 of them were treated with integrative traditional Chinese decoction QLYF. Patients were followed up for 2 years. Rate of adverse event occurrence, short-term clinical effects, long-term clinical effects, and TCM therapeutic evaluation were all compared. RESULTS: Total adverse event rate was lower in the QLYF group (χ 2 = 5.357, p = 0.022); rates of respiratory infection, urinary infection, poor appetite, hepatotoxity, cardiotoxicity, and neutropenia were all decreased in patients who received QLYF (p = 0.022); rates of respiratory infection, urinary infection, poor appetite, hepatotoxity, cardiotoxicity, and neutropenia were all decreased in patients who received QLYF (p = 0.022); rates of respiratory infection, urinary infection, poor appetite, hepatotoxity, cardiotoxicity, and neutropenia were all decreased in patients who received QLYF (p = 0.022); rates of respiratory infection, urinary infection, poor appetite, hepatotoxity, cardiotoxicity, and neutropenia were all decreased in patients who received QLYF (p = 0.022); rates of respiratory infection, urinary infection, poor appetite, hepatotoxity, cardiotoxicity, and neutropenia were all decreased in patients who received QLYF (p = 0.022); rates of respiratory infection, urinary infection, poor appetite, hepatotoxity, cardiotoxicity, and neutropenia were all decreased in patients who received QLYF (. CONCLUSION: Compared with merely using regular oral glucocorticoid plus cyclophosphamide pulse therapeutic regimen, the therapeutic regimen that integrates QLYF with the abovementioned western medicine might be a safe means to decrease the occurrence rate of adverse events and improve short-term and long-term clinical effects in children who suffered from moderately severe HSPN with nephrotic proteinuria.

Correlation between Traditional Chinese Medicine Symptom Patterns and the Renal Function, Immunologic Function Index, and Blood Coagulation Index in Patients with Henoch-Schönlein Purpura Nephritis.

OBJECTIVE: We investigate the correlation between the patterns of traditional Chinese medicine (TCM) syndromes and the damage of renal function, immunologic function index, and blood coagulation index in patients with Henoch-Schönlein purpura nephritis (HSPN) and thus provide the therapeutic effects of Chinese herbs decoction on HSPN. METHODS: We studied 262 hospitalized patients diagnosed with HSPN between 1 February 2016 and 1 January 2017. Indexes like renal function, immunologic function, and blood coagulation were measured. The patients were classified into four different patterns of TCM symptoms. RESULTS: In a total of 262 patients with HSPN, dampness-heat accumulation accounted for 59.5%, which is the highest proportion of TCM symptom patterns, liver-kidney yin deficiency accounted for 17.6%, qi and yin deficiency ratio reached 12.6%, and blood-heat bleeding accounted for 9.9%. 24-hour proteinuria was heavier in the dampness-heat accumulation patients who had immune disorders and were in hypercoagulative state and hyperfibrinolysis conditions. CONCLUSION: We analyzed and summarized the clinical characteristics of patients with HSPN and found that dampness-heat accumulation was dominant in patients and was always accompanied by immune disorders and coagulation disorders. These results provided the largest therapeutic effects of Chinese herbs decoction for clinical treatment.

[Ultrasonic imaging research at Ashi points in neck-type cervical spondylosis].

OBJECTIVE: To conduct the preliminary positioning and qualitative research of high-frequency ultrasonic imaging at Ashi points (including tender points and trigger points) in neck-type cervical spondylosis and explore the relevant law so as to provide the evidence for the selection of acupuncture scheme. METHODS: Thirty patients in compliance with the diagnostic criteria of neck-type cervical spondylosis were selected. The trigger points, tender points and placebo points were positioned on any of the three available oriented lines. The point-to-point high-frequency real-time dynamic ultrasonic imaging technology was used to scan and position each point and record the changes in ultrasound gradation anatomy and two-dimensional ultrasound in perimysium, two-dimensional and color Doppler ultrasonography and blood flow. The ultrasound characteristics were analyzed. RESULTS: ①Regarding the changes in ultrasound gradation anatomy and two-dimensional ultrasound in perimysium, the anatomic gradation at trigger points and tender points was in the sequence as cutaneous layer, subcutaneous fat layer, shallow muscular tissue layer, deep muscular tissue layer and vertebrae. The linear high echo presented in cutaneous layer; the low echo in subcutaneous fat layer; the linear high echo in muscular fasciae; the low echo in muscular layer and the clear linear echo in its perimysium; the high echo and declined posterior echo in vertebrae. Compared with the placebo points, 93.3% of trigger points (28/30) presented enhanced or thickened perimysium echo (P<0.05), and 96.7% of tender points (29/30) presented enhanced or thickened perimysium echo (P<0.05). The differences were not significant between the trigger points and the tender points (P>0.05). ②In the two-dimensional ultrasonography, the clear linear echo presented in perimysium, the enhanced or thickened echo in perimysium of trigger points and tender points. In the color Doppler ultrasonography, the blinking unstable dotted blood flow signal or stable short rod-like blood flow signal presented in the trigger points and tender points. ③Regarding the condition of blood flow, 56.7% of trigger points (17/30) presented Ⅱ degree of color blood flow signal and 83.3% of tender points (25/30) presented Ⅱ degree of color blood flow signal; 0% of placebo points presented Ⅱ degree of color blood flow signal. Compared with the placebo points, the differences in the rate of Ⅱ degree of color blood flow signal were significant statistically at both the trigger points and the tender points (both P<0.05). The difference was not significant between the trigger points and tender points (P>0.05). CONCLUSIONS: In the high-frequency ultrasound imaging at trigger points and tender points in neck-type cervical spondylosis, the ultrasound imaging characteristics present, which are similar between the trigger points and the tender points. The high-frequency ultrasound imaging is valuable in positioning and quantitative research of Ashi points in cervical spondylosis and has a certain significance to guide treatment.

[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.

Global DNA methylation variations after short-term heat shock treatment in cultured microspores of Brassica napus cv. Topas.

Heat stress can induce the cultured microspores into embryogenesis. In this study, whole genome bisulphite sequencing was employed to study global DNA methylation variations after short-term heat shock (STHS) treatments in cultured microspores of Brassica napus cv. Topas. Our results indicated that treatment on cultured Topas microspores at 32 °C for 6 h triggered DNA hypomethylation, particularly in the CG and CHG contexts. And the total number of T32 (Topas 32 °C for 6 h) vs. T0 (Topas 0 h) differentially methylated region-related genes (DRGs) was approximately two-fold higher than that of T18 (Topas 18 °C for 6 h) vs. T0 DRGs, which suggested that 32 °C might be a more intense external stimulus than 18 °C resulting in more changes in the DNA methylation status of cultured microspores. Additionally, 32 °C treatment for 6 h led to increased CHG differential methylations of transposons (DMTs), which were mainly constituted by overlaps between the hypomethylated differentially methylated regions (hypo-DMRs) and transposon elements (TEs). Further analysis demonstrated that the DRGs and their paralogs exhibited differential methylated/demethylated patterns. To summarize, the present study is the first methylome analysis of cultured microspores in response to STHS and may provide valuable information on the roles of DNA methylation in heat response.

Total synthesis, structural elucidation and anti-inflammatory activity evaluation of 2-deoxy-3,6-anhydro hexofuranoside derivatives isolated from Sauropus rostratus.

The first total synthesis of four 2-deoxy-3,6-anhydro hexofuranoside derivatives, namely sauropunols (A-D), isolated from the traditional Chinese medicinal plant Sauropus rostratus was accomplished. Structures of sauropunols A and B were clearly elucidated and reassigned. The anti-inflammatory activities of sauropunols (A-D) as well as the synthetic intermediates were evaluated, which is valuable for further structure-activity relationship (SAR) studies on this class of natural products.

Effect of Tongxinluo on Podocyte Apoptosis via Inhibition of Oxidative Stress and P38 Pathway in Diabetic Rats.

Diabetic nephropathy (DN) has been the leading cause of end-stage renal disease (ESRD). Podocyte apoptosis is a main mechanism of progression of DN. It has been demonstrated that activated P38 and caspase-3 induced by oxidative stress mainly account for increased podocyte apoptosis and proteinuria in DN. Meanwhile, Tongxinluo (TXL) can ameliorate renal structure disruption and dysfunction in DN patients in our clinical practice. However, the effect of TXL on podocyte apoptosis and P38 pathway remains unclear. To explore the effect of TXL on podocyte apoptosis and its molecular mechanism in DN, our in vivo and in vitro studies were performed. TXL attenuated oxidative stress in podocyte in DN in our in vivo and in vitro studies. Moreover, TXL inhibited the activation of P38 and caspase-3. Bcl-2 and Bax expression was partially restored by TXL treatment in our in vivo and in vitro studies. More importantly, TXL decreased podocyte apoptosis in diabetic rats and high glucose cultured podocyte. In conclusion, TXL protects podocyte from apoptosis in DN, partially through its antioxidant effect and inhibiting of the activation of P38 and caspase-3.

Effects of extremely low frequency pulsed magnetic fields on diabetic nephropathy in streptozotocin-treated rats.

BACKGROUND: Extremely low frequency pulsed magnetic fields (ELFPMF) have been shown to induce Faraday currents and measurable effects on biological systems. A kind of very high frequency electromagnetic field was reported that it improved the symptoms of diabetic nephropathy (DN) which is a major complication of diabetes. However, few studies have examined the effects of ELFPMF DN at the present. The present study was designed to investigate the effects of ELFPMF on DN in streptozotocin (STZ)-induced type 1 diabetic rats. METHODS: Adult male SD rats were randomly divided into three weight-matched groups: Control (non-diabetic rats without DN), DN + ELFPMF (diabetic rats with DN exposed to ELFPMF, 8 h/days, 6 weeks) and DN (diabetic rats with DN exposed to sham ELFPMF). Renal morphology was examined by light and electron microscopy, vascular endothelial growth factor (VEGF)-A and connective tissue growth factor (CTGF) were measured by enzyme linked immune sorbent assay. RESULTS: After 6 weeks' ELFPMF exposure, alterations of hyperglycemia and weight loss in STZ-treated rats with DN were not found, while both positive and negative effects of ELFPMF on the development of DN in diabetic rats were observed. The positive one was that ELFPMF exposure attenuated the pathological alterations in renal structure observed in STZ-treated rats with DN, which were demonstrated by slighter glomerular and tubule-interstitial lesions examined by light microscopy and slighter damage to glomerular basement membrane and podocyte foot processes examined by electron microscopy. And then, the negative one was that ELFPMF stimulation statistically significantly decreased renal expression of VEGF-A and statistically significantly increased renal expression of CTGF in diabetic rats with DN, which might partially aggravate the symptoms of DN. CONCLUSION: Both positive and negative effects of ELFPMF on the development of DN in diabetic rats were observed. The positive effect induced by ELFPMF might play a dominant role in the procession of DN in diabetic rats, and it is suggested that the positive effect should be derived from the correction of pathogenic diabetes-induced mediators.

Excess Retinoic Acid Induces Fusion of Centra by Degenerating Intervertebral Ligament Cells in Japanese flounder, Paralichthys olivaceus.

In marine aquaculture fish, excessive supplement of vitamin A (VA) to zooplanktons for larval culture and experimental exposure of larvae to retinoic acid (RA: active form of VA) have been known to cause vertebral deformity. However, the tissues in the developing vertebral column that are affected by RA and the progression of vertebral deformity remain undetermined. To examine these questions, we histologically traced the progress of vertebral deformity induced by RA in Japanese flounder (Paralichthys olivaceus). Larvae were exposed to RA for 3 days at mid-metamorphosis (G-stage), a critical stage for vertebral deformity. Intervertebral ligament, which is known to form intervertebral joints in cooperation with the notochord, was severely degenerated by RA, leading to fusion of centra. During further development to adult, growth of centra was severely suppressed in an anterior-posterior direction in RA-treated fish and the notochord tissue was lost from fused centra, resulting in complete loss of intervertebral joints and fusion of centra. We conclude that RA initially damages the intervertebral ligaments, and these defects lead to fusion, narrowing of centra, and loss of intervertebral joints in the vertebral column. The cumulative effect of these modifications is a truncated body form.

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.