Long non-coding RNA H19 regulates neurogenesis of induced neural stem cells in a mouse model of closed head injury

Stem cell-based therapies have been proposed as a potential treatment for neural regeneration following closed head injury.We previously reported that induced neural stem cells exert beneficial effects on neural regeneration via cell replacement.However,the neural regeneration efficiency of induced neural stem cells remains limited.In this study,we explored differentially expressed genes and long non-coding RNAs to clarify the mechanism underlying the neurogenesis of induced neural stem cells.We found that H19 was the most downregulated neurogenesis-associated lnc RNA in induced neural stem cells compared with induced pluripotent stem cells.Additionally,we demonstrated that H19 levels in induced neural stem cells were markedly lower than those in induced pluripotent stem cells and were substantially higher than those in induced neural stem cell-derived neurons.We predicted the target genes of H19 and discovered that H19 directly interacts with mi R-325-3p,which directly interacts with Ctbp2 in induced pluripotent stem cells and induced neural stem cells.Silencing H19 or Ctbp2 impaired induced neural stem cell proliferation,and mi R-325-3p suppression restored the effect of H19 inhibition but not the effect of Ctbp2 inhibition.Furthermore,H19 silencing substantially promoted the neural differentiation of induced neural stem cells and did not induce apoptosis of induced neural stem cells.Notably,silencing H19 in induced neural stem cell grafts markedly accelerated the neurological recovery of closed head injury mice.Our results reveal that H19 regulates the neurogenesis of induced neural stem cells.H19 inhibition may promote the neural differentiation of induced neural stem cells,which is closely associated with neurological recovery following closed head injury.

Green coffee bean extract improves obesity by decreasing body fat in high-fat diet-induced obese mice

Objective:To evaluate possible lipid catabolism and body fat regulation effects of 3-caffeoylquinic acid in Green coffee bean extract(GCBE) in high-fat diet(HFD)-induced obese mice.Methods:Obesity was induced in mice using a HFD for four weeks.Then,mice were fed only HFD or HFD with GCBE at 50,100,and 200 mg/kg.Fatty acid synthesis mechanism regulation of body fat was investigated through real-time PCR and Western blot assay.Body fat reduction was measured through dual-energy X-ray absorptiometry.Results:In HFD-induced obese mice,GCBE treatment significantly decreased body weight gain,liver weight and white adipose tissue weights with regulation of adipose tissue lipolysis hormones,like adiponectin and leptin.GCBE treatment decreased mR NA expression levels of adipogenesis and adipocyte metabolism related genes in adipose tissues and the liver,and decreased the corresponding protein expression.Dual energy X-ray absorptiometry measurements were used to compare body fat between mice on high-fat and those treated with GCBE.GCBE treated mice had a lower fat mass compared to HFD alone fed mice and relative body weight and fat mass were markedly decreased.Conclusions:GCBE has a potential anti-obesity effect with lowering body fat accumulation by regulating adipogenesis and lipid metabolism-related genes and proteins in WAT and liver.

Monascus pilosus-fermented black soybean inhibits lipid accumulation in adipocytes and in high-fat diet-induced obese mice

Objective:To explore the anti-obesity effects and the mechanism of action of Monascus pilosus(M.pilosus)-fermented black soybean(MFBS)extracts(MFBSE)and MFBS powders(MFBSP)in adipocytes and high-fat diet(HFD)-induced obese mice,respectively.Methods:Black soybean was fermented with M.pilosus,and the main constituents in MFBS were analyzed by HPLC analysis.In vitro,MFBSE were examined for anti-adipogenic effects using Oil-Red O staining.In vivo,mice were fed a normal-fat diet(NFD)control,HFD control or HFD containing 1 g/kg MFBSP for 12 weeks,and then body weight gain and tissues weight measured.Real-time PCR and western blot assay were used to determine the mechanism of anti-adipogenic effects.Results:MFBSE inhibited lipid accumulation in 3T3-L1 adipocytes without exerting cell cytotoxicity.MFBSP treatment in HFD-fed mice significantly decreased the body weight gain compared with the HFD control mice.MFBSE and MFBSP treatment resulted in significantly lower mRNA levels of adipogenesis-related genes,such as peroxisome proliferator-activated receptorγ(PPARγ),fatty acid-binding protein 4(FABP4),and fatty acid synthase(FAS),in adipocytes and in white adipose tissue(WAT)of HFD-induced obese mice.Conclusions:These results suggest that the anti-obesity effects of MFBS are elicited by regulating the expression of adipogenesis-related genes in adipocytes and WAT of HFDinduced obese mice.

Diet-Induced Thermogenesis

An immense amount of information has now accrued about the factors that influence the increment of heat and the efficiency with which the energy of food is used by different animal species. Heat increment is one of the major factors that decrease the efficiency of energy utilization. In growing animals, the free energy content of the basal ATP requirement is typically about one-third of dietary basal heat production （thermogenesis）. Thermogenesis is an evolutionary and biologically significant mechanism for adaptive, homeostatic heat production in animals, including shivering thermogenesis （ST）, nonshivering thermogenesis （NST）, diet-induced thermogenesis （DIT）, febrile response （fever）, and so on. The main focus of this review is on the effect of DIT on energy metabolism.

EFFECT OF HIGH-LIPID DIET ON GLOMERULAR MESANGIAL MATRIX IN ADRIAMYCIN-INDUCED NEPHROTIC RATS

OBJECTIVE: To determine the effect of hypercholsterolemia induced by a high-lipid diet on glomerulosclerosis. METHODS: Twenty nephrotic syndrome (NS) Wistar rats administrated adriamycin (ADR) with a single intravenous dose of 5 mg/kg body weight, were divided into the standard and high-lipid chow groups. Another 20 weight-matched non-NS rats that received a vehicle alone were grouped as control. Urinary protein excretion and serum cholesterol were assayed; image analysis and techniques of pathology, immunohistochemistry, and molecular biology were used to determine morphological changes in glomeruli and the production of glomerular mesangial matrices in different groups. RESULTS: The serum total cholesterol level was significantly higher in rats with high-lipid chow in both non-NS [(2.2 +/- 0.3) g/L vs. (0.9 +/- 0.1) g/L, P

Comparative study on the difference of obesity model induced by two kinds of high fat diet in Sprague-Dawley rats

Objective: To explore the differences of obese Sprague-Dawley(SD)rats model induced by lard oil high-fat(HF)diet or purified HF diet. Methods: SD weanling rats were randomly divided into three groups: D1 group,where rats were fed by lard oil HF diet;D2 group,where rats were fed by purified HF diet;C group,where rats were fed on chow. After 12 weeks,diet-induced obesity rat(stop 33% based on weight)were selected for further study,and the rest rats from group D1 and D2 were excluded. The food intake and weight were weighted daily and weekly,respectively. The subcutaneous,visceral and total fat contents of rats was measured by 256-row CT scan and the Lee index was calculated accordingly. The kidney,liver,testis,spleen and heart were weighted respectively. Serum leptin and insulin levels were quantified. The pathology in liver and adipose tissues were analyzed by HE staining. Oral glucose tolerance test(OGTT)was used to compare the glucose tolerance ability. Serum total cholestero(lT-CHO),high density lipoprotein(HDL-C),low density lipoprotein(LDL-C),triglyceride(TG)and inflammatory cytokines IL-6,TNF-α were detected as well. Results: After 12 weeks,the body weight,subcutaneous fat,visceral fat,total fat mass,wet weight of liver,kidney and heart,area under blood glucose curve and the levels of serum insulin,leptin,T-CHO,LDL-C,TG,IL-6 and TNF-α in group D2 were significantly increased compared to those of group C and group D1. HDL-C of group D2 was markedly lower than that in group C(P<0. 05). The visceral fat,total fat content and HDL-C in group D1 were significantly different from those of group C(P<0. 05). Steatosis and enlarged adipocyte were found in the livers of rats in group D1 and D2,and the lesions were more significant in group D2. Conclusion: Purified HF diet was more effective in inducing metabolic abnormalities,steatosis,peripheral chronic inflammation in obese SD rat models. But lard oil HF diet was more economical when only inducing visceral steatosis was required.

The Effects of Xylitol on Body Weight Loss Management and Lipid Profile on Diet-Induced Obesity Mice

Xylitol is an alternative sweetener which has been previously reported to have many beneficial effects such as prevention from dental caries, reduction of visceral fat and increased synthesis of collagen. However, its role in body weight loss management has not been uncovered before. This study sought to investigate the effects of xylitol on body weight loss management, blood glucose and lipid profile on diet-induced obesity (DOI) mice. Fifteen male mice were subjected to high fat diet (60 kcal%) and normal drinking water for 28 days and then randomly divided into three (control, glucose and xylitol) groups. Each group of mice was then fed with normal diet for another 28 days with supplied normal drinking water (control);glucose solution 10% and xylitol solution 10%. Body weight loss was found to be significantly high in xylitol mice (2.56 ± 0.21, p = 0.003) compared to the other two groups. Lowest blood glucose level was found in the control group mice with the mean 7.65 ± 0.10 (p = 0.001). Xylitol mice had also showed the lowest total cholesterol level (4.20 ± 0.90, p = 0.000) than the other groups, but highest in HDL level (2.72 ± 0.14, p = 0.000). In conclusion, these findings proved that xylitol has the potential to reduce body weight, lowering the blood glucose but yet increase the HDL level.

THE DIFFERENTIATION OF HUMAN GASTRIC ADENOCAR-CINOMA CELL LINE MGc80-3 INDUCED BY DIBUTYRYL cAMP IN VITRO

For providing some experimental basis in establishing malignant phenotypic reversed indexes of gastric carcinoma cells, human gastric adenocar-cinoma cell line MGc80-3 was induced by dBcAMP in vitro to appraise the effect of gastric carcinoma cell differentiation by chemical inducers.Under light microscope, MGc80-3 cells, after treated with 1 mM dBcAMP, tended to be flat and disperse, and their volume gradually enlarged, with their uncleus relatively smaller and their shape rather regular. Morphological changes, like norma differentiated epithelial cells, were observed. The cells attached firmly, grew slowly, their growth curve showed inhibitory rate amounted to 52.87%, and cellular division exponent displayed their peak value 1.5 times less than that of MGc80-3 cells. It was clear that dBcAMP could effectively inhibit the multiplication activity of MGc80-3 cells. After dBcAMP treatment, remarkable changes of cell surface charges was indicated by cell electrophoresis, the ratio dropped to 3.043 from 3.988, and their re-tardant ratio reached up to 31.2%. cAMP content in cells after this treatment, detected by cAMP and cGMP radioimmunoassay, was enhanced by 2.42 times, and cAMP/cGMP ratio, by 1.73 times. Thus, cAMP level within MGc80-3 cells was raised obviously by dBcAMP. Heterotransplantation experiments showed that tuntorigenic rate of MGc80-5 cells (transplanted subcutaneously to BALB/c mice) amounted to 100%, and that of the cells after this treatment was only 5.6%. Their tumorigenic ability was extremely reduced.These results confirmed that dBcAMP was able to change malignant phenotypic characteristics of MGc80-3 cells and produce a reversed alteration: Thus, it has a remarkable inductive effect in differentiating gastric carcinoma cells. All these characteristics were also considered as the reference indexes in appraising reversed effect for the homologous cancer cells.

Care strategies for patients with severe drug-induced hepatitis

Objective: The aim of this study is to analyse the clinical characteristics of 32 patients with severe drug-induced hepatitis, reinforce the practice of unique nursing and holistic nursing, improve the therapeutic effect, reduce the patients’ mortality, and increase their quality of life. Methods: We give patients individualized dietary guidance, medication nursing, and psychological care according to the characteristics of severe hepatitis and its complications, using com- prehensive medical treatment and combined signs of Traditional Chinese Medicine. Results: Overall, 22 (68.8%) out of 32 cases were improved, 8 (25.0%) cases died, and 2 (6.2%) cases were discharged of free will. In addition, the average hospital stay was 28.75 days. Conclusion: This study indicates that dietary guidance for the patients with severe drug-induced hepatitis varies with the individual. The result embodies the concept of Traditional Chinese Medicine that different treatment for the same disease and different diet for the same disease. Special nursing enriches the connotation of holistic nursing. Both of them are vital for improving the survival rate and promoting rehabilitation of patients with severe drug-induced hepatitis.

Multiple Ionization of Argon Induced by Carbon Ions at 20-500 keV/u Energies

We measure the multiple ionization cross-section ratios Rk1 of Ar impacted by Cw＋ （q= 1-3） ions in the energy range of 20-500 keV/u. The measured ratios Rkl increase with the projectile energy at lower energies, and reach the maximum at energies of 50-150 keV/u, then decrease for higher energies, We also use the classical over barrier ionization model to calculate the ratios Rk1, and the calculation results are in good agreement with the data, which suggest that the multiple ionization process is described by the sequential over-barrier ionization process,

The Intramolecular Coupling Reaction of 1,6-Bis(1-Alky1-2-Methylindol-3-yl)hexane-1,6-dione Induced by Low-valent Titanium

The intramolecular reductive coupling reaction of 1,6-bis(subshtuted indolyl)hexane-1,6-dione using zero-valent titanium reagent as catalyst proderes the novel photochromic 1,2-diheterocyclic cyclohexenes 2, together with unexpected compounds 3

The transverse laser induced thermoelectric voltages in step flow growth (1-x)Pb(Mg_(1/3)Nb_(2/3))O_(3-x)PbTiO_3 thin films

This paper reports that the transverse laser induced thermoelectric voltages （LITV） axe observed for the first time in the step flow growth （1- x）PD（Mg1/3Nb2/3）O3-xPbTiO3 （PMN-PT, x = 0.20, 0.33, 0.50） thin films deposited on vicinal-cut strontium titanate single crystal substrates. Because lead magnesium niobate-lead titanate is a solid solution of lead magnesium niobate （PMN） and lead titanate （PT）, there are two types of signals. One is wide with a time response of a microsecond, and the other superimposed with the wide signal is narrow with a time response of a nanosecond. The transverse LITV signals depend on the ratio of PMN to PT drastically. Under the irradiation of 28-ns pulsed KrF excimer laser with the 248-nm wavelength, the largest induced voltage is observed in the 0.50Pb（Mg1/3Nb2/3）O3-0.50 PbTiO3 films. Moreover, the effects of film thickness, substrates, and tilt angles of substrates are also investigated.

Anti-tumor effects induced by gene vaccines co-expressing truncated human prostate specific membrane antigen gene and mouse 4-1BBL

Objective To investigate the influence of m4-1BBL on anti-tumor effects induced by truncated human prostate specific membrane antigen ( tPSMA ) gene in mice. Methods A eukaryotic expression plasmid encoding tPSMA and m4-1BBL ( pDC316-tPSMA-IRES m4-1BBL) ,pDC316-tPSMA and pDC316 were constructed.

High Strain Rate Induced Plasticity-increasing of Metallic Materials under Tension

The effect of strain rate on plasticity has been Investigat-ed for three metallic materials with dynamic tension tech-nique. A phenomenon of high strain induced plasticity -increasing was found for tested materials. The elongation of quenched 30CrMnSiNi2A is 14. 5% under 40 m/s loading rate which is more than two times of the 7 % un-der 0. 5 mm/min. This typic high strain rate induced plasticity - Increasing phenomenon is associated with adiabatic heating, strain twinning and suppression of strain - induced - phase transformation.

High fat diet dysregulates microRNA-17-5p and triggers retinal inflammation:Role of endoplasmic-reticulum-stress

AIM To elucidate how high diet-induced endoplasmic reticulum-stress upregulates thioredoxin interacting protein expression in Müller cells leading to retinal inflammation. METHODS Male C57Bl/J mice were fed either normal diet or 60% high fat diet for 4-8 wk. During the 4 wk study, mice received phenyl-butyric acid(PBA); endoplasmic reticulum-stress inhibitor; for 2 wk. Insulin resistance was assessed by oral glucose tolerance. Effects of palmitate-bovine serum albumin(BSA)(400 μmol/L) were examined in retinal Müller glial cell line and primary Müller cells isolated from wild type and thioredoxin interacting protein knock-out mice. Expression of thioredoxin interacting protein, endoplasmic reticulum-stress markers, mi R-17-5p m RNA, as well as nucleotide-binding oligomerization domain-like receptor protein(NLRP3) and IL1β protein was determined.RESULTS High fat diet for 8 wk induced obesity and insulin resistance evident by increases in body weight and impaired glucose tolerance. By performing quantitative real-time polymerase chain reaction, we found that high fat diet triggered the expression of retinal endoplasmic reticulum-stress markers(P < 0.05). These effects were associated with increased thioredoxin interacting protein and decreased mi R-17-5p expression, whichwere restored by inhibiting endoplasmic reticulumstress with PBA(P < 0.05). In vitro, palmitate-BSA triggered endoplasmic reticulum-stress markers, which was accompanied with reduced mi R-17-5p and induced thioredoxin interacting protein m RNA in retinal Müller glial cell line(P < 0.05). Palmitate upregulated NLRP3 and IL1β expression in primary Müller cells isolated from wild type. However, using primary Müller cells isolated from thioredoxin interacting protein knock-out mice abolished palmitate-mediated increase in NLRP3 and IL1β.CONCLUSION Our work suggests that targeting endoplasmic reticulumstress or thioredoxin interacting protein are potential therapeutic strategies for early intervention of obesityinduced retinal inflammation.

Dietary Nε-(carboxymethyl)lysine affects cardiac glucose metabolism and myocardial remodeling in mice

BACKGROUND Myocardial remodeling is a key factor in the progression of cardiovascular disease to the end stage.In addition to myocardial infarction or stress overload,dietary factors have recently been considered associated with myocardial remodeling.Nε-(carboxymethyl)lysine(CML)is a representative foodborne toxic product,which can be ingested via daily diet.Therefore,there is a marked need to explore the effects of dietary CML on the myocardium.AIM To explore the effects of dietary CML(dCML)on the heart.METHODS C57 BL/6 mice were divided into a control group and a dCML group.The control group and the dCML group were respectively fed a normal diet or diet supplemented with CML for 20 wk.Body weight and blood glucose were recorded every 4 wk.^(18)F-fluorodeoxyglucose(FDG)was used to trace the glucose uptake in mouse myocardium,followed by visualizing with micro-positron emission tomography(PET).Myocardial remodeling and glucose metabolism were also detected.In vitro,H9C2 cardiomyocytes were added to exogenous CML and cultured for 24 h.The effects of exogenous CML on glucose metabolism,collagen I expression,hypertrophy,and apoptosis of cardiomyocytes were analyzed.RESULTS Our results suggest that the levels of fasting blood glucose,fasting insulin,and serum CML were significantly increased after 20 wk of dCML.Micro-PET showed that ^(18)F-FDG accumulated more in the myocardium of the dCML group than in the control group.Histological staining revealed that dCML could lead to myocardial fibrosis and hypertrophy.The indexes of myocardial fibrosis,apoptosis,and hypertrophy were also increased in the dCML group,whereas the activities of glucose metabolism-related pathways and citrate synthase(CS)were significantly inhibited.In cardiomyocytes,collagen I expression and cellular size were significantly increased after the addition of exogenous CML.CML significantly promoted cellular hypertrophy and apoptosis,while pathways involved in glucose metabolism and level of Cs mRNA were significantly inhibited.CONCLUSION This study reveals that dCML alters myocardial glucose metabolism and promotes myocardial remodeling.

Targeted anti-cancer therapy: Co-delivery of VEGF siRNA and Phenethyl isothiocyanate (PEITC) via cRGD-modified lipid nanoparticles for enhanced anti-angiogenic efficacy

Anti-tumor angiogenesis therapy, targeting the suppression of blood vessel growth in tumors, presents a potent approach in the battle against cancer. Traditional therapies have primarily concentrated on single-target techniques, with a specific emphasis on targeting the vascular endothelial growth factor, but have not reached ideal therapeutic efficacy. In response to this issue, our study introduced a novel nanoparticle system known as CS-siRNA/PEITC&L-cRGD NPs. These chitosan-based nanoparticles have been recognized for their excellent biocompatibility and ability to deliver genes. To enhance their targeted delivery capability, they were combined with a cyclic RGD peptide (cRGD). Targeted co-delivery of gene and chemotherapeutic agents was achieved through the use of a negatively charged lipid shell and cRGD, which possesses high affinity for integrin αvβ3 overexpressed in tumor cells and neovasculature. In this multifaceted approach, co-delivery of VEGF siRNA and phenethyl isothiocyanate (PEITC) was employed to target both tumor vascular endothelial cells and tumor cells simultaneously. The co-delivery of VEGF siRNA and PEITC could achieve precise silencing of VEGF, inhibit the accumulation of HIF-1α under hypoxic conditions, and induce apoptosis in tumor cells. In summary, we have successfully developed a nanoparticle delivery platform that utilizes a dual mechanism of action of anti-tumor angiogenesis and pro-tumor apoptosis, which provides a robust and potent strategy for the delivery of anti-cancer therapeutics.

Study on Bicoordination Chiral Inducement Catalysis of (R)-4-Thiazolidinecarboxylic Acid

The bicoordination chiral inducement catalysis of (R)-4-thiazolidinecarboxylic acid inthe enantioselective borane reduction of prochiral ketones has been studied. The fact that theabsolute configuration of the main product can be changed by simply using different operationmethods was firstly verified. And the reason of bicoordination chiral inducement was discussed.

高脂饮食对空间学习记忆功能的影响及齿状回N-甲基-D-天冬氨酸受体的调节作用

以刚断奶的大鼠为实验对象,进行长达12周的高脂饮食(high fat diet,HFD)(45%脂肪),观察大鼠的体质量及血脂和血糖水平,通过Morris水迷宫检测大鼠的空间学习和记忆能力;蛋白免疫印迹法检测海马齿状回(dentate gyrus,DG)区磷酸化的钙/钙调素依赖性蛋白激酶II(phosphorylated Ca^(2+)/calmodulin dependent protein kinase Ⅱ,p-CaMKⅡ)和环磷腺苷效应元件结合蛋白(phosphorylated cAMP-response element binding protein,p-CREB)以及神经炎症因子的表达;用蛋白免疫印迹法和免疫组织化学染色法观察DG区小胶质细胞标志物的表达,并通过往海马DG区注射N-甲基-D-天冬氨酸(N-methyl-D-aspartate,NMDA)受体阻断剂MK-801,观察DG区NMDA受体在上述改变中的作用。结果表明,与对照(control,CON)组比较,长期HFD诱发大鼠出现肥胖体态,即食源性肥胖(diet-induced obesity,DIO);与CON组比较,DIO组大鼠及DG区注射MK-801(DIO+MK)组的体质量及血清中的甘油三酯、总胆固醇和低密度脂蛋白的水平均显著增加;Morris水迷宫训练结果显示,与CON组比较,DIO组大鼠空间学习记忆功能损伤,而DG区微量注射MK-801可缓解上述损伤;与CON组比较,DIO组大鼠DG区p-CaMKII和p-CREB的表达显著降低,而离子钙结合衔接分子1、白介素-6(interleukin-6,IL-6)和IL-1β的表达却显著增加,但向海马DG区微量注射MK-801可反转上述变化。综上所述,长期HFD诱发大鼠的肥胖体态及神经炎症反应,并造成空间学习记忆功能损伤,而阻断海马DG区的NMDA受体可以提高CaMKII-CREB通路活性和减少神经炎症反应,改善DIO大鼠的空间学习和记忆损伤。本研究可为合理膳食及探明不良饮食习惯诱发的DIO影响记忆功能的机制提供理论依据。

Effect of mango seed kernel extract on the adipogenesis in 3T3-L1 adipocytes and in rats fed a high fat diet

Mangoes (Mangifera indica L.) are one of the most important tropical foods. The seed is one of the main by-products of mango processing. Therefore, it is important to find an economically viable use for this waste (e.g., as a food additive or supplement with high nutraceutical value). We investigated the anti-obesity effects of mango seed kernel extract with hot water (MSKE-W) in 3T3-L1 adipocytes and in a high fat diet (HFD)-induced obesity rat model. MSKE-W caused a significant decrease in the activity of glycerol 2-phosphate dehydrogenase in 3T3-L1 adipocytes without eliciting cell cytotoxicity and inhibited cellular lipid accumulation through down-regulation of transcription factors such as PPARγ and C/EBPα. In the animal model, rats fed an HFD containing 1% MSKE-W gained less weight than rats fed an HFD alone. The visceral fat mass in rats fed an HFD containing 1% MSKE-W tended to be lower than that in rats fed an HFD alone. Furthermore, histological examination of rat livers from an HFD showed steatohepatitis. However, rats on an HFD containning 1% MSKE-W showed no histopathological changes in liver tissue. Our results indicate that MSKE-W influences anti-obesity effects, both in vitro and in vivo, and suggest that MSKE-W provides a novel preventive potential against obesity.