Glycyrrhizin Prevents 7-Ketocholesterol Toxicity Against Differentiated PC12 Cells by Suppressing Mitochondrial Membrane Permeability Change

Defects in mitochondrial function participate in the induction of neuronal cell injury. In neurodegenerative conditions, oxidative products of cholesterol are elevated and oxysterols seem to be implicated in neuronal cell death. The present work was designed to study the inhibitory effect of licorice compounds glycyrrhizin and 18β-glycyrrhetinic acid against the toxicity of 7-ketocholesterol in relation to the mitochondria-mediated cell death process. 7-Ketocholesterol induced the nuclear damage, loss of the mitochondrial transmembrane potential, increase in the cytosolic Bax and cytochrome c levels, caspase-3 activation and cell death in differentiated PC12 cells. Glycyrrhizin and 18β-glycyrrhetinic acid prevented the 7-ketocholesterol-induced mitochondrial damage, leading to caspase-3 activation and cell death. The results obtained show that glycyrrhizin and 18β-glycyrrhetinic acid may prevent the 7-ketocholesterol-induced neuronal cell damage by suppressing changes in the mitochondrial membrane permeability.     

Protective parenting may have population-level consequences

In many animal species, recruitment is facilitated by adults’ efforts to protect offspring from predation. Theoretical studies of this phenomenon have usually focused on resolving the conflict between an individual's self-preservation and its attempts to successfully reproduce. While the decision to protect is made at the level of a single individual, the aggregation of these decisions may affect population density and structure. This idea motivates the development of a functional response for predators that is compatible with the protective behaviour of prey. We use this functional response to study the long-term behaviour of a protective prey population under different levels of predation. We find that contribution of protective effort may promote or inhibit population density depending on the riskiness associated with interference. Moreover, our results suggest that, in environments characterised by intense predation, a protection-driven Allee effect allows sufficiently large populations to persist. We interpret these results in the context of different strategies for newborn defence.     

Ischemic flap survival improvement by composition-selective fat grafting with novel adipose tissue derived product - stromal vascular fraction gel

Background

Flap necrosis due to insufficient blood supply is a common postoperative complication in random pattern flaps. Stem cell therapies have emerged as promising biologics for tissue ischemia. A novel fat derived product, stromal vascular fraction gel (SVF-gel), can be prepared with lipoaspirate through simple mechanical processing, removing only the lipid content. SVF-gel enriches adipose-derived stem cells and potentially beneficial for flap necrosis.

MMP-9基因多态性与缺血性脑卒中发病及预后的相关性研究

目的:研究基质金属蛋白酶9(MMP-9)基因多态性与缺血性脑卒中(IS)发病及预后的相关性,为IS的防治提供新的理论依据。方法:选取治疗的IS患者100例,根据TOAST分型标准分为大动脉粥样硬化型(LAA)组41例,小动脉阻塞型(SAO)组59例,并选取健康体检者40例作为对照组,采用PCR-RFLP法检测各组MMP-9基因C1562T、R279Q多态性,并对IS患者进行3个月的随访,采用Logistic回归分析C1562T、R279Q多态性与IS患者预后的相关性。结果:LAA组、SAO组MMP-9基因C1562T位点T等位基因、C/T+T/T基因型频数均高于对照组,差异有统计学意义(P0.05),LAA组、SAO组C1562T位点C等位基因、C/C基因型频数及R279Q位点等位基因和基因型频数与对照组比较差异无统计学意义(P0.05);Logistic回归分析显示,MMP-9各型别基因与预后无明显相关性(P0.05)。结论:MMP-9基因C1562T的T等位基因是IS发病的穿易感基因之一,但MMP-9基因多态性与IS患者的预后并无明显相关性。     

Intranasal immunisation with a 62 kDa proteinase combined with cholera toxin or CpG adjuvant protects against Trichomonas vaginalis genital tract infections in mice

Trichomonosis, caused by the protozoan parasite Trichomonas vaginalis, is one of the most frequent sexually transmitted diseases and is widely spread in all continents. Trichomonas vaginalis as well as other protozoan organisms have high levels of proteolitic activity mainly of the cysteine-proteinase type. This activity is necessary for recognition and adhesion of the parasite to the superficial epithelial cells of the host. In the present study, we show that intranasal immunisation with a 62 kDa cysteine-proteinase purified from T. vaginalis excretion-secretion products in combination with cholera toxin or with synthetic oligodeoxynucleotides (ODN) that contain unmethylated CpG motifs (CpG-ODN) elicits 62kDa specific IgG and IgA in vaginal lavage fluid and specific IgG in serum. This immunisation protocol resulted in enhanced elimination of parasites following intravaginal challenge of BALB/c mice.     

Calpain-induced Proteolysis After Transient Global Cerebral Ischemia and Ischemic Tolerance in a Rat Model

The activation of the [Ca²⁺]-dependent cysteine protease calpain plays an important role in ischemic injury. Here, the levels of two calpain-specific substrates, p35 protein and eukaryotic initiation factor 4G (eIF4G), as well as its physiological regulator calpastatin, were investigated in a rat model of transient global cerebral ischemia with or without ischemic tolerance (IT). Extracts of the cerebral cortex, whole hippocampus and hippocampal subregions after 30 min of ischemia and different reperfusion times (30 min and 4 h) were used. In rats without IT, the p35 levels slightly decreased after ischemia or reperfusion, whereas the levels of p25 (the truncated form of p35) were much higher than those in sham control rats after ischemia and remained elevated during reperfusion. The eIF4G levels deeply diminished after reperfusion and the decrease was significantly greater in CA1 and the rest of the hippocampus than in the cortex. By contrast, the calpastatin levels did not significantly decrease during ischemia or early reperfusion, but were upregulated after 4 h of reperfusion in the cortex. Although IT did not promote significant changes in p35 and p25 levels, it induced a slight increase in calpastatin and eIF4G levels in the hippocampal subregions after 4 h of reperfusion.     

Characterisation of the gene encoding a protective antigen from Babesia microti identified it as eta subunit of chaperonin containing T-complex protein 1.

Passive immunisations with a monoclonal antibody termed 1-5H showed a partial but significant inhibition of parasitaemia against Babesia microti challenge infection. By immunoscreening with 1-5H, a clone (termed p58 gene) was obtained from a cDNA expression library of B. microti and the complete nucleotide sequence was determined. A protein homology search showed significant amino acid identities to the η subunit of the chaperonin containing T-complex protein 1 (CCT) of human (59%), mouse (58%) and Plasmodium falciparum (62%). Genomic analyses indicated that the p58 gene is present as a single copy gene and contains a total of approximately 400-bp introns in the genome of B. microti. The mAb 1-5H recognised a 58-kDa protein of B. microti and was found to cross-react with a 60-kDa protein of Babesia rodhaini. These results suggest the possibility that the p58 protein is the CCT η subunit of B. microti and functions as a chaperonin.     

Protective effect of serotonin on 6-hydroxydopamine- and dopamine-induced oxidative damage of brain mitochondria and synaptosomes and PC12 cells

The present study elucidated the effects of indoleamines (serotonin, melatonin, and tryptophan) on oxidative damage of brain mitochondria and synaptosomes induced either by 6-hydroxydopamine (6-OHDA) or by iron plus ascorbate and on viability loss in dopamine-treated PC12 cells. Serotonin (1-100 microM), melatonin (100 microM), and antioxidant enzymes attenuated the effects of 6-OHDA, iron plus ascorbate, or 1-methyl-4-phenylpyridinium on mitochondrial swelling and membrane potential formation. Serotonin and melatonin decreased the attenuation of synaptosomal Ca(2+) uptake induced by either 6-OHDA alone or iron plus ascorbate. Serotonin and melatonin inhibited the production of reactive oxygen species, formation of malondialdehyde and carbonyls, and thiol oxidation in mitochondria and synaptosomes and decreased degradation of 2-deoxy-D-ribose. Unlike serotonin, melatonin did not reduce the iron plus ascorbate-induced thiol oxidation. Tryptophan decreased thiol oxidation and 2-deoxy-D-ribose degradation but did not inhibit the production of reactive oxygen species and formation of oxidation products in the brain tissues. Serotonin and melatonin attenuated the dopamine-induced viability loss, including apoptosis, in PC12 cells. The results suggest that serotonin may attenuate the oxidative damage of mitochondria and synaptosomes and the dopamine-induced viability loss in PC12 cells by a decomposing action on reactive oxygen species and inhibition of thiol oxidation and shows the effect comparable to melatonin. Serotonin may show a prominent protective effect on the iron-mediated neuronal damage.     

Human fetal aorta-derived vascular progenitor cells: identification and potential application in ischemic diseases

Vasculogenesis, the formation of blood vessels in embryonic or fetal tissue mediated by immature vascular cells (i.e., angioblasts), is poorly understood. Here we report a summary of our recent studies on the identification of a population of vascular progenitor cells (VPCs) in human fetal aorta. These undifferentiated mesenchymal cells co-express endothelial and myogenic markers (CD133+, CD34+, KDR+, desmin+) and are localized in outer layer of the aortic stroma of 11–12 weeks old human fetuses. Under stimulation with VEGF-A or PDGF-BB, VPCs give origin to a mixed population of mature endothelial and mural cells, respectively. When embedded in a three-dimensional collagen gel, VPCs organize into cohesive cellular cords that resembled mature vascular structures. The therapeutic efficacy of a small number of VPCs transplanted into ischemic limb muscle was demonstrated in immunodeficient mice. Investigation of the effect of VPCs on experimental heart ischemia and on diabetic ischemic ulcers in mice is in progress and seems to confirm their efficacy. On the whole, fetal aorta represents an important source for the investigation of phenotypic and functional features of human vascular progenitor cells.