What Can We Learn from FGF-2 Isoform-Specific Mouse Mutants? Differential Insights into FGF-2 Physiology In Vivo

Fibroblast growth factor 2 (FGF-2), ubiquitously expressed in humans and mice, is functionally involved in cell growth, migration and maturation in vitro and in vivo. Based on the same mRNA, an 18-kilo Dalton (kDa) FGF-2 isoform named FGF-2 low molecular weight (FGF-2LMW) isoform is translated in humans and rodents. Additionally, two larger isoforms weighing 21 and 22 kDa also exist, summarized as the FGF-2 high molecular weight (FGF-2HMW) isoform. Meanwhile, the human FGF-2HMW comprises a 22, 23, 24 and 34 kDa protein. Independent studies verified a specific intracellular localization, mode of action and tissue-specific spatiotemporal expression of the FGF-2 isoforms, increasing the complexity of their physiological and pathophysiological roles. In order to analyze their spectrum of effects, FGF-2LMW knock out (ko) and FGF-2HMWko mice have been generated, as well as mice specifically overexpressing either FGF-2LMW or FGF-2HMW. So far, the development and functionality of the cardiovascular system, bone formation and regeneration as well as their impact on the central nervous system including disease models of neurodegeneration, have been examined. This review provides a summary of the studies characterizing the in vivo effects modulated by the FGF-2 isoforms and, thus, offers a comprehensive overview of its actions in the aforementioned organ systems.     

Vitamin D Compounds PRI-2191 and PRI-2205 Enhance Anastrozole Activity in Human Breast Cancer Models

1,25-Dihydroxycholecalciferol, the hormonally active vitamin D₃ metabolite, is known to exhibit therapeutic effects against breast cancer, mainly by lowering the expression of estrogen receptors and aromatase activity. Previously, the safety of the vitamin D active metabolite (24R)-1,24-dihydroxycholecalciferol (PRI-2191) and 1,25(OH)₂D₃ analog PRI-2205 was tested, and the in vitro activity of these analogs against different cancer cell lines was studied. We determined the effect of the two vitamin D compounds on anastrozole (An) activity against breast cancer based on antiproliferative activity, ELISA, flow cytometry, enzyme inhibition potency, PCR, and xenograft study. Both the vitamin D active metabolite and synthetic analog regulated the growth of not only estrogen receptor-positive cells (T47D and MCF-7, in vitro and in vivo), but also hormone-independent cancer cells such as SKBR-3 (HER-2-positive) and MDA-MB-231 (triple-negative), despite their relatively low VDR expression. Combined with An, PRI-2191 and PRI-2205 significantly inhibited the tumor growth of MCF-7 cells. Potentiation of the antitumor activity in combined treatment of MCF-7 tumor-bearing mice is related to the reduced activity of aromatase by both An (enzyme inhibition) and vitamin D compounds (switched off/decreased aromatase gene expression, decreased expression of other genes related to estrogen signaling) and by regulation of the expression of the estrogen receptor ERα and VDR.     

樟芝多糖通过降低NLRP3 Caspase1炎性小体表达改善帕金森小鼠神经行为学的机制研究

目的:研究樟芝多糖通过降低NLRP3-Caspase1炎性小体表达改善6-OHDA构建的帕金森小鼠模型的行为学机制。方法:利用6-OHDA脑内注射构建帕金森小鼠模型，通过酪氨酸羟化酶（TH）免疫组化染色和行为学判定小鼠模型的构建成功。利用樟芝多糖进行干预，分别在干预前、干预后的第1、3、7天4个时间点进行神经行为学实验，分别采用转棒实验、爬杆实验检测小鼠自主行为能力以及协调能力，4个时间点取小鼠尾静脉外周血采用ELISA法检测外周血中Caspase1和IL-1β的表达，樟芝多糖干预第7天时待进行完行为学实验后小鼠断颈处死，取小鼠脑组织-纹状体，Western blot法检测纹状体中Caspase1、proCaspase1、NLRP3的表达，高效液相色谱检测纹状体中单胺类神经递质的表达，RT-QPCR检测Caspase1、NLRP3、IL-1β、IL-4、IL-6的mRNA表达。NISSl染色检测小鼠脑组织神经细胞凋亡情况。 结果:6-OHDA脑内注射可以造成小鼠帕金森样病变，且TH蛋白表达显著下调，樟芝多糖干预后小鼠的行为学得到显著改善（P<0.05），纹状体中Caspase1、proCaspase1、NLRP3的表达显著下调，与模型小鼠相比具有统计学差异（P<0.05），且相关炎症因子Caspase1、NLRP3、IL-1β、IL-4、IL-6的mRNA表达下调（P<0.05），纹状体中单胺类神经递质表达上升（P<0.05）。结论:樟芝多糖可以通过下调NLRP3-Caspase1炎性小体表达来改善6-OHDA构建的帕金森小鼠模型行为改善，这可能是樟芝多糖治疗帕金森的机制之一。     

Consumption of solutions containing sodium chloride is enhanced in female oxytocin-deficient mice.

Intact and ovariectomized oxytocin (OT)-deficient (OT-/-) and wild-type (OT+/+) mice were tested for consumption of 0.5 M NaCl solution or tap water in a 2-bottle choice test. During 3 days of acclimation, voluntary ingestion of NaCl was equal between genotypes. After overnight fluid deprivation, intact OT-/- mice ingested 2 times more NaCl solution than OT+/+ mice in the 6th hr, but not the 1 st hr, after reintroduction of fluid. Ovariectomized mice consumed less than intact mice after overnight fluid deprivation. When a 0.2 M NaCl solution was administered for 6 days in ovariectomized mice, OT-/- mice voluntarily consumed greater amounts than OT+/+ mice. After overnight fluid deprivation, consumption by OT-/- mice was 3 times that of OT+/+ mice at 1 hr and 2-fold greater after 6 hr. Enhanced intake of NaCl-containing solutions in female OT-/- mice suggests that central OT may be an important inhibitor of sodium consumption. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Vasopressin and the transmission of paternal behavior across generations in mated, cross-fostered Peromyscus mice.

The role of arginine vasopressin (AVP) in the nongenomic transfer of paternal behavior from fathers to offspring was examined in Peromyscus. Male California mice (P. californicus) exposed to fewer retrievals by white-footed mouse (P. leucopus) foster parents displayed fewer retrievals of biological offspring. In contrast, white-footed mice were retrieved equally rarely by California mouse foster parents and by biological parents and displayed no changes in pup retrieval behavior. AVP-immunoreactive staining in the bed nucleus of the stria terminalis may predict paternal behavior because it correlated positively with retrievals and with a score consisting of huddling, grooming, and time inside the nest. The authors discuss AVP as a possible mechanism by which early experience shapes adult paternal behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

^125I,^131I诱发小鼠精子畸形发生率比较

本文选用 ICR 雄性小鼠,经腹腔分别注射不同剂量的~(125)I 及~(131)I,观察并比较它们对小鼠精子畸形发生率的影响及染毒后睾丸中放射性活度的变化。实验结果表明:(1)~(125)I 染毒后4—5周,0、185、370和555 kBq 各组精子畸形发生率分别为9.00‰、9.57‰、11.6‰及13.9‰;~(131)I 染毒后4—5周,上述各组精子畸形发生率分别为8.50‰、12.5‰、14.7‰和15.5‰;在相同注入量下,~(125)I 与~(131)I 诱发小鼠精子畸形发生率的差异各组均不显著(X~2检验,p>0.05)。(2)~(125)I、~(131)I 染毒后2h 至7天内,两者在睾丸中的放射性活度及变化规律相似,即在染毒后2h 达最高值,每克睾丸中~(125)I 和~(131)I 的放射性活度分别占初始注入量(370 kBq)的0.72％和0.50％,然后迅速下降,至一周时,仅分别占初始注入量的0.035％和0.011％。     

Biological Effects of Flammulina Velutipes Richin RE on Chinese Kunming Mice

ＢｉｏｌｏｇｉｃａｌＥｆｆｅｃｔｓｏｆＦｌａｍｍｕｌｉｎａＶｅｌｕｔｉｐｅｓＲｉｃｈｉｎＲＥｏｎＣｈｉｎｅｓｅＫｕｎｍｉｎｇＭｉｃｅＬｉａｎｇＤｉｎｇｂａｎｇ（梁定邦）；ＣｕｉＤｅｆａｎｇ（崔德芳）；ＺｈａｎｇＪｉｎｔｏｎｇ（张金桐）（Ｄｅｐａｒｔｍ...     

Distinct Expression Patterns of Cxcl12 in Mesenchymal Stem Cell Niches of Intact and Injured Rodent Teeth

Specific stem cell populations within dental mesenchymal tissues guarantee tooth homeostasis and regeneration throughout life. The decision between renewal and differentiation of stem cells is greatly influenced by interactions with stromal cells and extracellular matrix molecules that form the tissue specific stem cell niches. The Cxcl12 chemokine is a general marker of stromal cells and plays fundamental roles in the maintenance, mobilization and migration of stem cells. The aim of this study was to exploit Cxcl12-GFP transgenic mice to study the expression patterns of Cxcl12 in putative dental niches of intact and injured teeth. We showed that endothelial and stromal cells expressed Cxcl12 in the dental pulp tissue of both intact molars and incisors. Isolated non-endothelial Cxcl12⁺ dental pulp cells cultured in different conditions in vitro exhibited expression of both adipogenic and osteogenic markers, thus suggesting that these cells possess multipotent fates. Taken together, our results show that Cxcl12 is widely expressed in intact and injured teeth and highlight its importance as a key component of the various dental mesenchymal stem cell niches.     

Effectiveness of cardenolides as feeding deterrents toPeromyscus mice

I compared the feeding responses of five species ofPeromyscus mice (aztecus, polionotus, melanotis, leucopus, andmaniculatus) to three bitter-tasting cardenolides (ouabain, digoxin, and digitoxin) that differ greatly in lipophilic character.Peromyscus, like other muroid rodents, are unusual in that they can ingest relatively large amounts of cardenolides without adverse physiologic effects. In experiment 1, I determined avoidance thresholds for the three cardenolides with 48 hr, two-choice tests. Mice exhibited large interspecific differences in avoidance threshold, and the interspecific ranking of the thresholds (maniculatus=leucopus >melanotis >polionotus >aztecus) was the same for each of the cardenolides. In experiment 2, I reevaluated the avoidance thresholds, but this time monitored the pattern of intake (i.e., bout lengths) during initial feeding encounters with cardenolidelaced diets. For each cardenolide, mice were subjected to three tests. In test 1, they received a control diet; in test 2, a diet containing the cardenolide at a concentration 1 log, unit below the avoidance threshold (as determined in experiment 1); and in test 3, a diet containing the cardenolide at the avoidance threshold concentration. Results were similar across all species and cardenolide types: Bout lengths in tests 1 and 2 were statistically equal, whereas those in test 3 were significantly shorter than those in test 1. The rapid rejection of cardenolide-laced diets in test 3 is consistent with a preingestive (i.e., gustatory) mechanism underlying the avoidance thresholds. I conclude (1) thatPeromyscus species differ substantially in taste sensitivity to cardenolides and that these differences may influence each species' respective ability to eat cardenolide-laced insects; and (2) that a species' relative taste sensitivity to one cardenolide predicts its sensitivity to other cardenolides.