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1.
Honokiol, a biphenyl-type neolignan, which shows the remarkable neurotrophic effect in primary cultured rat cortical neurons, has been effectively synthesized in 21% yield over 14 steps starting from 5-bromosalicylic acid and p-hydroxybenzoic acid by utilizing Pd-catalyzed Suzuki-Miyaura coupling reaction as a key step. Additionally, the structure-activity relationship between neurite outgrowth-promoting activity and its O-methylated and/or its hydrogenated analogues was examined in the primary cultures of fetal rat cortical neurons, suggesting that 5-allyl and 4'-hydroxyl groups are essential for affecting the neurotrophic activity of honokiol.  相似文献   
2.
    
Thoracic aortic dissection (TAD) is an aortic disease associated with dysregulated extracellular matrix composition and de-differentiation of vascular smooth muscle cells (SMCs). Growth Differentiation Factor 11 (GDF11) is a member of transforming growth factor β (TGF-β) superfamily associated with cardiovascular diseases. The present study attempted to investigate the expression of GDF11 in TAD and its effects on aortic SMC phenotype transition. GDF11 level was found lower in the ascending thoracic aortas of TAD patients than healthy aortas. The mouse model of TAD was established by β-aminopropionitrile monofumarate (BAPN) combined with angiotensin II (Ang II). The expression of GDF11 was also decreased in thoracic aortic tissues accompanied with increased inflammation, arteriectasis and elastin degradation in TAD mice. Administration of GDF11 mitigated these aortic lesions and improved the survival rate of mice. Exogenous GDF11 and adeno-associated virus type 2 (AAV-2)-mediated GDF11 overexpression increased the expression of contractile proteins including ACTA2, SM22α and myosin heavy chain 11 (MYH11) and decreased synthetic markers including osteopontin and fibronectin 1 (FN1), indicating that GDF11 might inhibit SMC phenotype transition and maintain its contractile state. Moreover, GDF11 inhibited the production of matrix metalloproteinase (MMP)-2, 3, 9 in aortic SMCs. The canonical TGF-β (Smad2/3) signalling was enhanced by GDF11, while its inhibition suppressed the inhibitory effects of GDF11 on SMC de-differentiation and MMP production in vitro. Therefore, we demonstrate that GDF11 may contribute to TAD alleviation via inhibiting inflammation and MMP activity, and promoting the transition of aortic SMCs towards a contractile phenotype, which provides a therapeutic target for TAD.  相似文献   
3.
    
The use of PARP inhibitors in combination with radiotherapy is a promising strategy to locally enhance DNA damage in tumors. Loss of XRCC2 compromises DNA damage repairs, and induced DNA damage burdens may increase the reliance on PARP-dependent DNA repairs of cancer cells to render cell susceptibility to PARP inhibitor therapy. Here we tested the hypothesis that XRCC2 loss sensitizes colorectal cancer (CRC) to PARP inhibitor in combination with radiotherapy (RT). We show that high levels of XRCC2 or PARP1 in LARC patients were significantly associated with poor overall survival (OS). Co-expression analyses found that low levels of PARP1 and XRCC2 were associated with better OS. Our in vitro experiments indicated that olaparib+IR led to reduced clonogenic survival, more DNA damage, and longer durations of cell cycle arrest and senescence in XRCC2-deficient cells relative to wild-type cells. Furthermore, our mouse xenograft experiments indicated that RT + olaparib had greater anti-tumor effects and led to long-term remission in mice with XRCC2-deficient tumors. These findings suggest that XRCC2-deficient CRC acquires high sensitivity to PARP inhibition after IR treatment and supports the clinical development for the use of olaparib as a radiosensitizer for treatment of XRCC2-deficient CRC.Subject terms: Colorectal cancer, Prognostic markers  相似文献   
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Candida is the most common human fungal pathogen and causes systemic infections that require neutrophils for effective host defense. Humans deficient in the C-type lectin pathway adaptor protein CARD9 develop spontaneous fungal disease that targets the central nervous system (CNS). However, how CARD9 promotes protective antifungal immunity in the CNS remains unclear. Here, we show that a patient with CARD9 deficiency had impaired neutrophil accumulation and induction of neutrophil-recruiting CXC chemokines in the cerebrospinal fluid despite uncontrolled CNS Candida infection. We phenocopied the human susceptibility in Card9-/- mice, which develop uncontrolled brain candidiasis with diminished neutrophil accumulation. The induction of neutrophil-recruiting CXC chemokines is significantly impaired in infected Card9-/- brains, from both myeloid and resident glial cellular sources, whereas cell-intrinsic neutrophil chemotaxis is Card9-independent. Taken together, our data highlight the critical role of CARD9-dependent neutrophil trafficking into the CNS and provide novel insight into the CNS fungal susceptibility of CARD9-deficient humans.  相似文献   
6.
Nuclear apoptosis induced by isolated mitochondria   总被引:2,自引:0,他引:2  
Jiang ZF  Zhao Y  Hong X  Zhai ZH 《Cell research》2000,10(3):221-232
We isolated and purified mitochondria from mouse livers and spinach leaves.When added into egg extracts of Xenopus laevis,they caused nuclei of mouse liver to undergo apoptotic changes.Chromatin condensation,margination and DNA ladder were observed.After incubating isolated mitochondria in some hypotonic solutions,and centrifuging these mixtures at mgh speed,we got mitochondrial supernatants.It was found that in the absence of cytosolic factor,the supernatant alone was able to induce apoptotic changes in nuclei.The effective components were partly of protein.DNA fragmentation was partly inhibited by caspase inhibitors AC-DEVD-CHO and AC-YVAD-CHO.Meanwhile,caspase inhibitors fully blocked chromatin condensation.Primary characterization of the nuclear endonuclease(s) induced by mitochondrial supernatants was also conducted.It was found that this endonuclease is different from endonuclease G,cytochrome c-induced nuclease,or Ca^2 -activated endonuclease.  相似文献   
7.
A storage root-bearing somatic hybrid was produced for the first time by protoplast fusion between sweetpotato (Ipomoea batatas (L.) Lam.) cv. Kokei No. 14 and its wild relative I. triloba L. Protoplasts isolated from embryogenic suspension cultures of Kokei No. 14 were fused with petiole protoplasts of I. triloba L. using polyethylene glycol-mediated protocol. Fusion products were cultured in a modified Murashige and Skoog medium containing 0.05 mg l−1 2,4-dichlorophenoxyacetic acid (2,4-D) and 0.5 mg l−1 kinetin. A total of 176 plants were obtained from 42 out of 134 calluses derived from fused protoplasts, and 91 of these plants were confirmed to be somatic hybrids through peroxidase isozyme, random amplified polymorphic DNA, amplified fragment length polymorphism, and cytological analyses. Upon transfer into soil and grown in the greenhouse and then to the field, 100% survival was observed. A single plant, designated KT1, was found to produce storage roots. Genomic in situ hybridization analysis confirmed presence of chromosomes from both parents and recombinant chromosomes in KT1. Drought tolerance, dry matter content, soluble sugar content, and fertility of this somatic hybrid were evaluated for potential use in sweetpotato breeding.  相似文献   
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9.
The genomic organization and expression of genes of the T-cell receptor gamma (TRG) locus are described for mice and humans, but not for species such as rabbits (Oryctolagus cuniculus), in which T cells compose a sizeable proportion of T cells in the periphery. We cloned 200 kb of the rabbit TRG locus and determined the TRGV gene usage in adult and newborn rabbits by RT-PCR. We identified two TRGJ genes, one TRGC gene, and 22 TRGV genes, all of which encoded functional variable regions. One TRGV gene is the unique member of the TRGV2 subgroup, whereas the other genes belong to the TRGV1 subgroup. Evolutionary analyses of TRGV1 genes identified three distinct groups that can be explained by separate duplication events in the rabbit genome. Evidence of gene conversion between TRGV1.1 and TRGV1.6 was observed. Both TRGV1 and TRGV2 subgroup genes were expressed in the spleen, intestine, and appendix of adult rabbits, and the repertoire of TRGV genes expressed in these tissues was similar. In these tissues from newborns, and in skin from adults, only the genes from the TRGV1 subgroup were expressed. Greater TRGV-J junctional diversity was found in tissues from adult compared to newborn rabbits. Our analyses indicate rabbits have a larger germ line encoded TRG repertoire compared with that of mice and humans. In addition, we found TRGV gene usage is alike in most tissues of rabbits similar to that found in humans but in contrast to that found in mice.Electronic SupplementaryMaterial Supplementary material is available for this article at The nucleotide sequence data reported in this article have been submitted to GenBank and are assigned the accession numbers AY748325–AY748348  相似文献   
10.

Background and Purpose

To study the MRI findings of otic and sinus barotrauma in patients with carbon monoxide(CO) poisoning during hyperbaric oxygen (HBO) therapy and examine the discrepancies of otic and sinus abnormalities on MRI between barotrauma and acute otitis media with effusion.

Materials and Methods

Eighty patients with CO-poisoning diagnosed with otic and sinus barotrauma after HBO therapy were recruited. Brain MRI was performed to predict delayed encephalopathy. Over the same period, 88 patients with acute otitis media with effusion on MRI served as control. The abnormalities of the middle ear and paranasal sinuses on MRI were noted and were compared between groups. Nine patients with barotrauma were followed up by MRI.

Results

In the barotrauma group, 92.5% of patients had bilateral middle ear abnormalities on MRI, and 60% of patients had both middle ear cavity and mastoid cavity abnormalities on MRI in both ears. Both rates were higher than those in the control group (p = 0.000). In the two groups, most abnormalities on MRI were observed in the mastoid cavity. The rate of sinus abnormalities of barotrauma was 66.3%, which was higher than the 50% in the control group (p = 0.033). In the nine patients with barotrauma followed up by MRI, the otic barotrauma and sinus abnormalities had worsened in 2 patients and 5 patients, respectively.

Conclusion

MRI is able to depict the abnormalities of otic and sinus barotrauma in patients with CO-poisoning during HBO therapy and to differentiate these from acute otitis media with effusion.  相似文献   
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