Natural products as modulators of the nuclear receptors and metabolic sensors LXR,FXR and RXR

Nuclear receptors (NRs) represent attractive targets for the treatment of metabolic syndrome-related diseases. In addition, natural products are an interesting pool of potential ligands since they have been refined under evolutionary pressure to interact with proteins or other biological targets.This review aims to briefly summarize current basic knowledge regarding the liver X (LXR) and farnesoid X receptors (FXR) that form permissive heterodimers with retinoid X receptors (RXR). Natural product-based ligands for these receptors are summarized and the potential of LXR, FXR and RXR as targets in precision medicine is discussed.     

Naltrexone partially inhibits the estrogen-induced increase in prolactin secretion and anterior pituitary weight

The effects of naltrexone, a specific opiate antagonist, on stimulation by estradiol benzoate (EB) of prolactin (PRL) release and anterior pituitary (AP) weight, were studied in gonadectomized female and male Sprague-Dawley rats. One week after castration, rats were injected for 10 days once daily with 2 μg EB alone, or together with twice daily injections of 2 mg naltrexone/kg body weight (BW). Blood was collected for radioimmunoassay of PRL by orbital sinus puncture on days 0 and 6, and by decapitation on day 11, at which time the AP was quickly removed, weighed and assayed for PRL.Serum PRL concentrations and AP weights were significantly increased by EB administration. These effects of EB were partially but significantly inhibited by naltrexone. These results suggest that endegenous opiates may be involved in the estrogen-induced rise in serum PRL and increase in pituatary weight.     

Crenation and cupping of the red cell: A new theoretical approach. Part II. Cupping

Typical, axisymmetrical cup shaped cells have been carefully measured and the shapes analyzed mathematically. The results show that the strain energy of a cup shaped cell is always higher than that of a biconcave cell except when the two layers of the membrane involved in resistance to bending are free to slide over one another. This is true whether intrinsic curvature of the membrane is positive, negative or zero. If the two layers can slide over one another, the cup shape becomes the lower energy form. Shear resistance, if appreciable, must cause the cup cell to buckle. Photomicrographs of cup shaped cells show buckled configurations characteristic of those of a partly deflated thin-walled rubber ball, which is a similar object having a low ratio of bending/shear strength.In light of these findings, the cup shape of the red cell can no longer be considered as evidence of intrinsic membrane curvature of opposite sign to that of the crenated cell, but appears to indicate a phase change either in the hydrophobic interior of the bimolecular membrane or in some equivalent interface.     

一次性电击引起大鼠脑内突触结构可塑性变化的定量观察

运用电镜,对一次性电击引起大鼠脑内Ｇｒａｙ Ⅰ型突触界面某些结构的变化进行了定量观察。在海马ＣＡ３区,突触后膜致密物质显著增厚（Ｐ〈０．０５）,突触间隙宽度极显著增宽（Ｐ〈０．０１）;在大脑皮层感觉运动区,突触界面曲率显著变大（Ｐ〈０．０５）。突触界面弯曲类型无显著性差异。结果提示：一次性电击可以引起大鼠脑内突触界面结构发生可塑性变化。     

Nucleostemin基因在卵巢上皮性肿瘤的表达及与病理分型的关系

目的：研究核干细胞因子Nucleostemin（NS）基因在卵巢上皮性肿瘤中的表达,探讨其与肿瘤病理分型的关系。方法：采用RT-PCR及Western blot检测36例卵巢癌组织手术标本,32例卵巢良性上皮肿瘤组织手术标本,12例正常卵巢组织标本中Nu-cleostemin基因及相应蛋白的表达,采用分组对照的方法对比3组样本中NS基因及蛋白的表达情况,并进行相对定量研究。采用统计学方法检测NS基因的表达是否与临床病理分级及血清CA125存在关联。结果：①卵巢癌组织中NS的阳性表达率显著高于良性肿瘤组织及正常卵巢组织;②卵巢癌组织中,淋巴结转移组NS的表达水平高于未转移组;③临床分期Ⅲ期组的表达水平高于ⅠB期组;④中、低分化组的表达水平高于高分化组。结论：卵巢癌组织中存在NS基因的高表达,其表达量与组织类型无关,而与临床TNM分期及组织分级正相关。     

Proteomic analysis of secretion from human transplanted submandibular gland replacing lacrimal gland with severe keratoconjunctivitis sicca

Purpose: Proteomic analysis of secretions from transplanted or non-transplanted submandibular glands in patients with severe keratoconjunctivitis sicca and tears from normal eyes. Experimental design: Secretions from submandibular glands transplanted to replace lacrimal glands and non-transplanted submandibular glands were collected at 1 year from 5 patients with severe keratoconjunctivitis sicca undergoing transplantation, and tears were collected from 3 normal subjects. 2-D electrophoresis (2-DE), then mass spectrometry was used to identify proteins. Western blot analysis was used to confirm protein expression. Results: We identified 34 and 11 distinct proteins in the saliva from transplanted submandibular glands and tears, respectively. The saliva from transplanted submandibular glands contained almost all the proteins abundant in tear fluid. The functions of identified proteins in the saliva from transplanted submandibular gland were mainly immune response and anti-bacterial. In total, 7 proteins showed differential expression between the saliva of transplanted and non-transplanted submandibular glands. The upregulation of short palate, lung and nasal epithelium carcinoma-associated protein 2 and carbonic anhydrase VI was confirmed by Western blot analysis. Conclusions: Identified proteins in saliva from transplanted submandibular glands may protect ocular structures. These findings can help in understanding the functional status of transplanted submandibular glands.     

经阴道三维超声联合CA125、CA199、NLR及PLR检测对绝经后子宫内膜癌的诊断效能

摘要 目的：探讨经阴道三维超声联合糖类抗原125（CA125）、糖类抗原199（CA199）、中性粒细胞/淋巴细胞比值（NLR）及血小板/淋巴细胞比值（PLR）检测对绝经后女性子宫内膜癌（EC）的诊断效能。方法：回顾性分析本院2019年5月至2022年5月收治的因绝经后出血就诊的92例疑似子宫内膜肿瘤患者的病历资料,经手术病理证实,EC患者48例（EC组）、子宫内膜良性病变患者44例（良性组）。比较两组CA125、CA199、NLR及PLR水平,对比两组子宫内膜血管指数（VI）、血流指数（FI）、血管-血流指数（VFI）、子宫内膜容积（EV）变化及血流信号分布情况。绘制受试者工作特征（ROC）曲线分析经阴道三维超声联合CA125、CA199、NLR及PLR检测对绝经后EC的诊断效能。结果：EC组CA125、CA199、NLR及PLR水平均高于良性组（P＜0.05）。EC组三维超声参数VI、FI、VFI及EV均高于良性组（P＜0.05）。EC组血流信号Ⅱ级占比25.00%,Ⅲ级占比70.83%;良性组血流信号Ⅱ级占比88.64%,Ⅲ级占比2.27%。EC组血流信号Ⅱ级占比低于良性组,血流信号Ⅲ级占比高于良性组（P＜0.05）。两组血流信号0级、Ⅰ级比较无差异（P＞0.05）。ROC结果显示五项检查联合检测曲线下面积（AUC）值为0.944（95%Cl：0.902~0.985）,具有更优的诊断效能（敏感度为89.10%、特异度为91.80%）。结论：CA125、CA199、NLR及PLR检测联合经阴道三维超声检查诊断绝经后EC效果显著,可为临床诊断提供参考。     

DISC1-related signaling pathways in adult neurogenesis of the hippocampus

Disrupted-in-schizophrenia 1 (DISC1) is a multifunctional scaffold protein which plays an important role in neurogenesis and neural development in the adult brain, especially in the dentate gyrus (DG) of the hippocampus. Accumulated research has unveiled the role of DISC1 in several aspects of neural development and neurogenesis, such as neuronal maturation, proliferation, migration, positioning, differentiation, dendritic growth, axonal outgrowth, and synaptic plasticity. Studies on the function of this protein have explored multiple facets, including variants and missense mutants in genetics, proteins interactivity and signaling pathways in molecular biology, and pathogenesis and treatment targets of major mental illness, and more. In this review, we present several signaling pathways discussed in recent research, such as the AKT signaling pathway, GABA signaling pathway, GSK3β signaling pathway, Wnt signaling pathway, and NMDA-R signaling pathway. DISC1 interacts, directly or indirectly, with these signaling pathways and they co-regulate the process of adult neurogenesis in the hippocampus.     

MPTP modulates hippocampal synaptic transmission and activity-dependent synaptic plasticity via dopamine receptors

Parkinson's disease (PD)-like symptoms and cognitive deficits are inducible by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP). Since cognitive abilities, including memory formations rely also on hippocampus, we set out to clarify the effects of MPTP on hippocampal physiology. We show that bath-application of MPTP (25?μM) to acute hippocampal slices enhanced AMPA receptor-mediated field excitatory postsynaptic potentials (AMPAr-fEPSPs) transiently, whereas N-methyl-D-aspartate (NMDA) receptor-mediated fEPSPs (NMDAr-fEPSPs) were facilitated persistently. The MPTP-mediated transient AMPAr-fEPSP facilitation was antagonized by the dopamine D2-like receptor antagonists, eticlopride (1?μM) and sulpiride (1 and 40?μM). In contrast, the persistent enhancement of NMDAr-fEPSPs was prevented by the dopamine D1-like receptor antagonist SCH23390 (10?μM). In addition, we show that MPTP decreased paired-pulse facilitation of fEPSPs and mEPSCs frequency. Regarding activity-dependent synaptic plasticity, 25?μM MPTP transformed short-term potentiation (STP) into a long-term potentiation (LTP) and caused a slow onset potentiation of a non-tetanized synaptic input after induction of LTP in a second synaptic input. This heterosynaptic slow onset potentiation required activation of dopamine D1-like and NMDA-receptors. We conclude that acute MPTP application affects basal synaptic transmission by modulation of presynaptic vesicle release and facilitates NMDAr-fEPSPs as well as activity-dependent homo- and heterosynaptic plasticity under participation of dopamine receptors.