2-O-β-D-Glucopyranosyl-L-ascorbic acid,an ascorbic acid derivative isolated from the fruits of Lycium barbarum L.,ameliorates high fructose-induced neuroinflammation in mice:involvement of gut microbiota and leaky gut

Western diet(rich in highly refined sugar and fat)can induce a range of metabolic dysfunctions in animals and humans,including neuroinflammation and cognitive function decline.Neuroinflammation and cognitive impairment,two critical pathological characteristics of Alzheimer’s disease,have been closely associated with microbial alteration via the gut-brain axis.Thus,the present study aimed to investigate the influence of 2-O-β-D-glucopyranosyl-L-ascorbic acid(AA-2βG)isolated from the fruits of Lycium barbarum on preventing the high-fructose diet(HFrD)induced neuroinflammation in mice.It was found that AA-2βG prevented HFr D-induced cognitive deficits.AA-2βG also predominantly enhanced the gut barrier integrity,decreased lipopolysaccharide entry into the circulation,which subsequently countered the activation of glial cells and neuroinflammatory response.These beneficial effects were transmissible by horizontal fecal microbiome transplantation,transferring from AA-2βG fed mice to HFr D fed mice.Additionally,AA-2βG exerted neuroprotective effects involving the enrichment of Lactobacillus and Akkermansia,potentially beneficial intestinal bacteria.The present study provided the evidence that AA-2βG could improve indices of cognition and neuroinflammmation via modulating gut dybiosis and preventing leaky gut.As a potential functional food ingredient,AA-2βG may be applied to attenuate neuroinflammation associated with Western-style diets.

The Effects of Different Fixation Methods on Quality of Lycium ruthenicum Murr Bud-tea

The effects of three fixation methods( steaming,blanching and microwave fixation) on chemical composition and sensory quality of Lycium ruthenicum bud-tea were investigated.The results showed the fixation technique( the leaf weight 3 g/cm^2,the time 1.5 min,and the temperature 100 ℃) was the best,which was beneficial to the conservation of free amino acid and soluble sugar in L.ruthenicum bud-tea.The loss of chlorophyll was limited,and the score of sensory quality review was higher.

VEGF-B prevents excessive angiogenesis by inhibiting FGF2/FGFR1 pathway

Although VEGF-B was discovered as a VEGF-A homolog a long time ago,the angiogenic effect of VEGF-B remains poorly understood with limited and diverse findings from different groups.Notwithstanding,drugs that inhibit VEGF-B together with other VEGF family members are being used to treat patients with various neovascular diseases.It is therefore critical to have a better understanding of the angiogenic effect of VEGF-B and the underlying mechanisms.Using comprehensive in vitro and in vivo methods and models,we reveal here for the first time an unexpected and surprising function of VEGF-B as an endogenous inhibitor of angiogenesis by inhibiting the FGF2/FGFR1 pathway when the latter is abundantly expressed.Mechanistically,we unveil that VEGF-B binds to FGFR1,induces FGFR1/VEGFR1 complex formation,and suppresses FGF2-induced Erk activation,and inhibits FGF2-driven angiogenesis and tumor growth.Our work uncovers a previously unrecognized novel function of VEGF-B in tethering the FGF2/FGFR1 pathway.Given the anti-angiogenic nature of VEGF-B under conditions of high FGF2/FGFR1 levels,caution is warranted when modulating VEGF-B activity to treat neovascular diseases.

O-羧甲基壳聚糖提高生物药剂学分类系统Ⅱ类药物溶解度能力的研究

目的探究羧甲基壳聚糖作为过饱和药物递送系统载体提高生物药剂学分类系统Ⅱ类药物溶解度的潜力,为难溶性药物的辅料选择提供新的参考。方法选择O-CMCS、N-CMCS两种羧甲基壳聚糖聚合物作为研究对象,瑞格列奈作为模型药物。首先将聚合物与药物进行分子对接,通过打分函数预测聚合物与药物的相互作用;其次,使用溶剂转移法,验证分子对接结果,考察聚合物的沉淀抑制能力。制备瑞格列奈与羧甲基壳聚糖的固体分散体,进行差式扫描量热、红外光谱表征,以及非漏槽条件溶出试验研究。结果分子对接结果显示:N-CMCS和O-CMCS与瑞格列奈的结合能分别为-4.95、-7.60 kcal·mol^(-1),O-CMCS与瑞格列奈结合效果较好,具有3个强氢键的结合。溶剂转移法实验也证明:O-CMCS的沉淀抑制能力优于N-CMCS。制剂表征结果显示:固体分散体中的瑞格列奈呈无定形状态,通过强氢键与O-CMCS进行结合。非漏槽条件下的溶出结果显示:50%载药量的固体分散体溶出率为原料药的7倍,且维持过饱和浓度长达24 h。结论O-CMCS通过氢键与模型药物瑞格列奈相互结合,可促进药物溶出,抑制沉淀析出,维持较长时间的过饱和浓度。提示O-CMCS具有作为过饱和药物递送系统载体的潜力,为难溶性药物辅料的选择提供了新的参考。

LC-MS/MS法测定人血浆中沙芬酰胺浓度及其在中国健康人体内的药动学研究

目的:建立LC-MS/MS法测定人血浆中沙芬酰胺的浓度,并进行中国健康人体内的药动学研究。方法:20名健康中国志愿者单次口服100 mg甲磺酸沙芬酰胺片,分别于服药前1 h内(0 h)和服药后0.5,1.0,1.33,1.67,2.0,2.33,2.67,3.0,3.5,4.0,5.0,6.0,8.0,12.0,24.0,48.0,72.0,96.0 h采集静脉血,采用建立的LC-MS/MS方法测定血浆中沙芬酰胺的浓度;再用Phoenix Win Non Lin 7.0软件统计药动学参数。结果:血浆中沙芬酰胺的线性范围为2.000~1 200 ng·m L-1(r=0.998 6),日内、日间RSD均<15%。20名健康中国志愿者口服100 mg甲磺酸沙芬酰胺片后,AUC0-t为(22 266.011±3 529.258)μg·L-1·h-1;AUC0-∞为(23 584.528±3 978.137)μg·L-1·h-1;MRT0-t为(25.873±2.238)h;t1/2为(23.048±3.035)h;Tmax为(1.875±1.579)h;Vz/F为(28.731±4.848)L·kg-1;CLz/F为(0.873±0.155)L·h-1·kg-1;Cmax为(907.185±198.323)μg·L-1。结论:建立的LC-MS/MS方法快速、灵敏、准确、专属性强、重复性好,适用于血浆中沙芬酰胺浓度的测定。沙芬酰胺吸收较快,半衰期长。

黑果枸杞花色苷Pt3G对前列腺癌LNCaP和PC-3细胞增殖与凋亡的影响

有报道指出,花色苷对疾病具有一定的化学预防活性.黑果枸杞富含花色苷,具有多种生物活性.本实验前期研究发现,黑果枸杞花色苷Pt3G可通过ROS/PTEN/PI3K/Akt途径抑制前列腺癌DU145细胞的增殖.本研究针对另外2种前列腺癌细胞LNCaP和PC-3进一步探讨黑果枸杞花色苷Pt3G抑制前列腺癌细胞的作用及其相关机制.采用甲基噻唑基四唑比色法检测细胞增殖、流式细胞术和TdT介导的dUTP缺口末端标记技术(TdT-mediated dUTP nick-end labeling,TUNEL)法检测细胞凋亡以及蛋白印迹法检测相关蛋白的表达.结果表明,Pt3G以浓度依赖性方式抑制细胞增殖,其抑制LNCaP和PC-3细胞的半数抑制浓度分别为601.97和445.79μg/mL.流式细胞术和TUNEL检测发现,Pt3G能够诱导前列腺癌LNCaP和PC-3细胞凋亡,并促进细胞周期阻滞在S期.而且,不同浓度Pt3G处理前列腺癌细胞24 h后,细胞抗凋亡因子PI3K、p-PI3K、Akt、p-Akt的表达水平显著降低,而促凋亡因子Bax、Cytochrome c、caspase 3、cleaved caspase 3的表达显著升高.此外,研究还发现,Pt3G可以激活LNCaP和PC-3细胞的PTEN蛋白并刺激细胞ROS的过量产生来诱导LNCaP和PC-3细胞凋亡.综上,本研究进一步证明了黑果枸杞花色苷Pt3G可能通过ROS/PTEN/PI3K/Akt/caspase 3途径抑制LNCaP和PC-3细胞增殖并促进细胞凋亡.因此,黑果枸杞花色苷Pt3G可能是预防或治疗前列腺癌的一种潜在抗增殖剂.

烟气影响他莫昔芬及吲哚昔芬在大鼠肿瘤组织分布的机制

目的研究烟气对他莫昔芬及吲哚昔芬在大鼠肿瘤组织分布的影响机制。方法将50只甲基亚硝基脲诱导的♀SD模型大鼠随机分为对照组与吸烟试验组,均单剂量10 mg·kg-1他莫昔芬灌胃,通过LC-MS/MS检测血浆和肿瘤组织中他莫昔芬和吲哚昔芬的浓度,通过qRT-PCR和Western blot检测肿瘤组织中乳腺癌耐药蛋白(Bcrp) mRNA和蛋白水平的表达。结果 HE染色显示:对照组肿瘤组织出现浸润性乳腺癌细胞特征;试验组中血浆和肿瘤组织中待测物浓度均降低;试验组肿瘤组织Bcrp mRNA水平和蛋白水平均显著高于对照组。结论烟气通过诱导肿瘤组织Bcrp的表达,减少了他莫昔芬、吲哚昔芬在肿瘤组织中的分布;吲哚昔芬受到Bcrp外排作用影响,可能是Bcrp的底物。