Biomedical subjects

Jun Liu

Publications and source records attributed to Jun Liu.

At least 37 records · Page 2Linked to original sources

PubMed2006

Plasmodium yoelii: distinct CD4(+)CD25(+) regulatory T cell responses during the early stages of infection in susceptible and resistant mice.

The outcome of experimental murine infection with different strains of malaria parasites, ranging from spontaneous cure to death, depends largely on the establishment of effective Th1 responses during the early stages of infection. Here we describe the disparity in CD4(+)CD25(+) regulatory T cell (Treg) responses during the early stages of infection with the highly virulent Plasmodium yoelii 17XL strain in susceptible (BALB/c) and resistant (DBA/2) mice. An increased proportion of Tregs 3-4 days post inoculation, co-occurring with elevated IL-10 levels, is observed in BALB/c but not in DBA/2 mice. These findings suggest that Treg proliferation might be causally associated with the suppression of Th1 responses during early malaria infection, leading to increase parasitemia and mortality in BALB/c mice, possibly in an IL-10-dependent manner.

Animals↗

PubMed2006

CAP interacts with cytoskeletal proteins and regulates adhesion-mediated ERK activation and motility.

CAP/Ponsin belongs to the SoHo family of adaptor molecules that includes ArgBP2 and Vinexin. These proteins possess an N-terminal sorbin homology (SoHo) domain and three C-terminal SH3 domains that bind to diverse signaling molecules involved in a variety of cellular processes. Here, we show that CAP binds to the cytoskeletal proteins paxillin and vinculin. CAP localizes to cell-extracellular matrix (ECM) adhesion sites, and this process requires binding to vinculin. Overexpression of CAP induces the aggregation of paxillin, vinculin and actin at cell-ECM adhesion sites. Moreover, CAP inhibits adhesion-dependent processes such as cell spreading and focal adhesion turnover, whereas a CAP mutant that is unable to localize to cell-ECM adhesion sites is incapable of exerting these effects. Finally, depletion of CAP by siRNA-mediated knockdown leads to enhanced cell spreading, migration and the activation of the PAK/MEK/ERK pathway in REF52 cells. Taken together, these results indicate that CAP is a cytoskeletal adaptor protein involved in modulating adhesion-mediated signaling events that lead to cell migration.

Animals↗

PubMed2006

Surface-mediated growth of transparent, oriented, and well-defined nanocrystalline anatase titania films.

A new, surface-mediated method to grow transparent, oriented, and well-defined nanocrystalline anatase TiO2 films has been developed. The morphology of crystals is tunable from octahedral pyramids to truncate octahedral pyramids. These novel nanocrystalline films could have implications not only for practical applications but also for understanding the structure and orientation dependent properties of the important anatase material.

Journal Article↗

PubMed2006

Protein-protein interactions mediate mitochondrial cholesterol transport and steroid biosynthesis.

Transport of cholesterol into the mitochondria is the rate-determining, hormone-sensitive step in steroid biosynthesis. Here we report that the mechanism underlying mitochondrial cholesterol transport involves the formation of a macromolecular signaling complex composed of the outer mitochondrial membrane translocator protein (TSPO), previously known as peripheral-type benzodiazepine receptor; the TSPO-associated protein PAP7, which binds and brings to mitochondria the regulatory subunit RIalpha of the cAMP-dependent protein kinase (PKARIalpha); and the hormone-induced PKA substrate, steroidogenic acute regulatory protein (StAR). Hormone treatment of MA-10 Leydig cells induced the co-localization of TSPO, PAP7, PKARIalpha, and StAR in mitochondria, visualized by confocal microscopy, and the formation in living cells of a high molecular weight multimeric complex identified using photoactivable amino acids. The hormone-induced recruitment of exogenous TSPO in this complex was found to parallel the increased presence of 7-azi-5alpha-cholestan-3beta-ol in the samples. Co-expression of Tspo, Pap7, PkarIalpha, and Star genes resulted in the stimulation of steroid formation in both steroidogenic MA-10 and non-steroidogenic COS-F2-130 cells that were engineered to metabolize cholesterol. Disruption of these protein-protein interactions and specifically the PKARIalpha-PAP7 and PAP7-TSPO interactions, using PAP7 mutants where the N0 area homologous to dual A-kinase-anchoring protein-1 or the acyl-CoA signature motif were deleted or using the peptide Ht31 known to disrupt the anchoring of PKA, inhibited both basal and hormone-induced steroidogenesis. These results suggest that the initiation of cAMP-induced protein-protein interactions results in the formation of a multivalent scaffold in the outer mitochondrial membrane that mediates the effect of hormones on mitochondrial cholesterol transport and steroidogenesis.

Animals↗

PubMed2006

Enriched environment treatment restores impaired hippocampal synaptic plasticity and cognitive deficits induced by prenatal chronic stress.

Prenatal stress can cause long-term effects on cognitive functions in offspring. Hippocampal synaptic plasticity, believed to be the mechanism underlying certain types of learning and memory, and known to be sensitive to behavioral stress, can be changed by prenatal stress. Whether enriched environment treatment (EE) in early postnatal periods can cause a recovery from these deficits is unknown. Experimental animals were Wistar rats. Prenatal stress was evoked by 10 foot shocks (0.8 mA for 1s, 2-3 min apart) in 30 min per day at gestational day 13-19. After weaning at postnatal day 22, experimental offspring were given the enriched environment treatment through all experiments until tested (older than 52 days age). Electrophysiological and Morris water maze testing was performed at 8 weeks of age. The results showed that prenatal stress impaired long-term potentiation (LTP) but facilitated long-term depression (LTD) in the hippocampal CA1 region in the slices. Furthermore, prenatal stress exacerbated the effects of acute stress on hippocampal LTP and LTD, and also impaired spatial learning and memory in the Morris water maze. However, all these deficits induced by prenatal stress were recovered by enriched environment treatment. This work observes a phenomenon that may contribute to the understanding of clinically important interactions among cognitive deficit, prenatal stress and enriched environment treatment. Enriched environment treatment on early postnatal periods may be one potentially important target for therapeutic interventions in preventing the prenatal stress-induced cognitive disorders.

Animals↗

PubMed2006

Hemoglobin-degrading plasmepsin II is active as a monomer.

A family of aspartic proteases called plasmepsins is important for hemoglobin degradation in intraerythrocytic Plasmodium parasites. Plasmepsin II (PM II) is the best studied member of this family. PM II and its close orthologs and paralogs form homodimers with extensive interfaces in all known crystal structures. This raised the question whether the homodimer is the functional subunit of plasmepsins in solution. We have used gel filtration chromatography, site-directed mutagenesis, and analytical ultracentrifugation to study the oligomeric status of PM II in solution. Our results reveal that PM II exists mainly as a monomer in solution and that the monomer is fully functional for catalysis. A hydrophobic loop at the PM II monomer surface, which would be buried in a PM II dimer, is shown to be essential for the hemoglobin degradation capability of PM II.

Aspartic Acid Endopeptidases↗

PubMed2006

Substitution mapping in dahl rats identifies two distinct blood pressure quantitative trait loci within 1.12- and 1.25-mb intervals on chromosome 3.

Substitution mapping was used to refine the localization of blood pressure (BP) quantitative trait loci (QTL) within the congenic region of S.R-Edn3 rats located at the q terminus of rat chromosome 3 (RNO3). An F2(SxS.R-Edn3) population (n=173) was screened to identify rats having crossovers within the congenic region of RNO3 and six congenic substrains were developed that carry shorter segments of R-rat-derived RNO3. Five of the six congenic substrains had significantly lower BP compared to the parental S rat. The lack of BP lowering effect demonstrated by the S.R(ET3x5) substrain and the BP lowering effect retained by the S.R(ET3x2) substrain together define the RNO3 BP QTL-containing region as approximately 4.64 Mb. Two nonoverlapping substrains, S.R(ET3x1) and S.R(ET3x6), had significantly lower BP compared to the S strain, indicating the presence of two distinct BP QTL in the RNO3 q terminus. The RNO3 q terminus was fine mapped with newly developed polymorphic markers to characterize the extent of the congenic regions. The two RNO3 BP QTL regions were thus defined as within intervals of 0.05-1.12 and 0.72-1.25 Mb, respectively. Also important was our difficulty in fine mapping and marker placement in this portion of the rat genome (and thus candidate gene identification) using the available genomic data, including the rat genome sequence.

Animals↗

PubMed2006

Calcific aortic valve disease should not be considered as a degenerative disease anymore.

Calcific aortic valve disease is common among the elderly. Until recently, the concept that calcific aortic valve disease is a degenerative and unmodifiable process basically induced by long-lasting mechanical stress was generally accepted. However calcific aortic valve disease is not merely related to age-associated "wear and tear". The development and progression of calcific aortic valve disease are based on an active process that shares a number of similarities with atherosclerosis. Statins and angiotensin-converting enzyme inhibitors have been shown to slow calcium accumulation in aortic valves. Thus, calcific aortic valve disease should not be considered as a degenerative disease anymore.

Aged↗

PubMed2006

Atrial fibrillation: rhythm control offers no advantage over rate control for some, but not all.

Atrial fibrillation (AF) is not a benign condition. Although AF is the most common sustained cardiac arrhythmia, the management of AF remains controversial. In recent years, several clinical trials comparing rhythm control with rate control for AF management found that rhythm control offers no advantage over rate control, but the findings may not apply equally to all patients. The main point is the high risk of AF recurrence in these trials and the toxic effects and poor efficacy of presently available antiarrhythmic drugs negate the benefit of rhythm control. Rhythm control should be considered as the preferred initial therapy if sinus rhythm had been maintained in a higher proportion of patients. For the moment, the optimal strategy to treat AF should be individualized, with a bias towards rate control if patients are at high risk for arrhythmias or can be kept asymptomatic. Rhythm control may still be justified in younger patients or patients who still have symptoms despite adequate rate control. In addition, patients with new or first-episode AF often warrant at least an initial trial of rhythm control.

Anti-Arrhythmia Agents↗

PubMed2006

Disruption of MEF2 activity in cardiomyoblasts inhibits cardiomyogenesis.

Myocyte enhancer factors (MEF2s) bind to muscle-specific promoters and activate transcription. Drosophila Mef2 is essential for Drosophila heart development, however, neither MEF2C nor MEF2B are essential for the early stages of murine cardiomyogenesis. Although Mef2c-null mice were defective in the later stages of heart morphogenesis, differentiation of cardiomyocytes still occurred. Since there are four isoforms of MEF2 factors (MEF2A, MEF2B, MEF2C and MEF2D), the ability of cells to differentiate may have been confounded by genetic redundancy. To eliminate this variable, the effect of a dominant-negative MEF2 mutant (MEF2C/EnR) during cardiomyogenesis was examined in transgenic mice and P19 cells. Targeting the expression of MEF2C/EnR to cardiomyoblasts using an Nkx2-5 enhancer in the P19 system resulted in the loss of both cardiomyocyte development and the expression of GATA4, BMP4, Nkx2-5 and MEF2C. In transiently transgenic mice, MEF2C/EnR expression resulted in embryos that lacked heart structures and exhibited defective differentiation. Our results show that MEF2C, or genes containing MEF2 DNA-binding sites, is required for the efficient differentiation of cardiomyoblasts into cardiomyocytes, suggesting conservation in the role of MEF2 from Drosophila to mammals.

Animals↗

PubMed2006

A critical review of analytical ultracentrifugation and field flow fractionation methods for measuring protein aggregation.

Analytical ultracentrifugation (AUC) and field flow fractionation (FFF) are 2 important biophysical methods for measuring protein aggregates. Both methods can separate protein monomer from its aggregate forms under a broad range of solution conditions. Recent advances in instrumentation and data analysis, particularly in the field of analytical ultracentrifugation technology, have significantly improved the capability and sensitivity of these biophysical methods for detecting protein aggregates. These advances have resulted in an increased use of these methods in the biopharmaceutical industry for characterization of therapeutic proteins. However, despite their many advantages over conventional methods, the difficulty in the use of the instrumentation and the complexity of data analysis process, have often hampered the widespread use and proper interpretation of data. This article reviews the recent progress in both technologies, and a few case studies are also presented to discuss their advantages and limitations.

Biological Products↗

PubMed2006

Stereoselective synthesis of jaspine B from D-xylose.

The natural cytotoxic marine compound, jaspine B, is stereoselectively synthesized from D-xylose in 11 linear steps with a 23.9% overall yield. The key step in the synthesis involves an iodine-induced debenzylation of a primary alcohol and the subsequent 2,5-cyclization to fit the required configuration of jaspine B. A preliminary bioassay shows strong inhibition activities against human MDA231, Hela, and CNE cell lines, indicating potential usage in various cancer treatments.

Antineoplastic Agents↗

PubMed2006

[A comparison of T3 sympathectomy versus T4 sympathectomy in the treatment of primary palmer hyperhidrosis].

OBJECTIVE: To evaluate the effect and side effect of T(3) versus T(4) sympathectomy in the surgical management of primary palmar hyperhidrosis through prospective multi-center randomized controlled trial. METHODS: From Sep 2004 to Feb 2006, 106 consecutive patients (49 males and 54 females) with primary palmar hyperhidrosis were enrolled in the study and randomly assigned into T(3) or T(4) level sympathectomy groups. 66 patients received T(3) sympathetic chain transection and 37 patients received T(4) sympathetic chain transection. The two groups were comparable in all other parameters. RESULTS: All procedures were carried out successfully without severe morbidity or mortality. After a mean follow-up period of 8.6 months, both groups remained satisfactory in palmar sweating control. The T(4) group had more moisture hands compared with the T(3) branch (54.1% vs 15.2%, P < 0.01), but this didn't compromise the patients' satisfactory. The patients in T(4) group showed significantly less dry hand problems than the patients in the T(3) group (5.4% vs. 25.8%, P < 0.05), and so did compensatory sweating (21.6% vs. 45.6%, P < 0.05). CONCLUSION: The procedure of T(3) or T(4) sympathectomy, both transecting the sympathetic chain in one single position in relatively lower segment, are comparatively effective in the treatment of primary palmar hyperhidrosis, but T(4) sympathectomy shows less side effect.

Adolescent↗

PubMed2006

[Evaluation of clinical management strategies for atypical squamous cells of undetermined significance in cervical cytology].

OBJECTIVE: To evaluate the 3 different clinical management strategies for patients with cervical cytological atypical squamous cells of undetermined significance (ASC-US) recommended by the guideline of The 2001 Bethesda system and the 2001 American Society for Colposcopy and Cervical Pathology (ASCCP). METHODS: 1394 patients with a cytopathological diagnosis of ASC-US by use of liquid-based thin-layer preparation were managed by three different clinical strategies, and evaluated by the percentage of histological diagnosis > or = high-grade intraepithelial lesion (HSIL), i.e., cervical intraepithelial neoplasia (CIN2 and 3) as standard. 421 patients in Group A underwent colposcopically directed cervical biopsy, 475 patients in Group B were followed-up after 6 months by cytology, colposcopy and biopsy were performed if the results were > or = ASC-H or ASC-US and HPV-DNA (+). 498 patients in Group C: underwent HC-II test, colposcopy and biopsy were performed on those aged > or = 30 and with the HPV-DNA (+), if the patients were aged < 30 and with the HPV-DNA (+), HC-II test and cytology would be performed after 6 months; colposcopy and biopsy were performed on those with the results > or = ASC-H or HPV-DNA (+). RESULTS: (1) The results of histological diagnosis > or = CIN2 were found in 27 cases (6.41%) of Group A, 26 cases (5.78%) of Group B, and 34 cases (6.91%) of Group C. There was no statistically significant difference among these 3 groups (all P > 0.05). (2) Convenience was significantly different among these 3 groups (P < 0.01). The workloads for the doctors and the discomfort resulting from biopsy for the patients were the greatest in Group A. The patient's compliance of Group B was low because of the necessity to wait for follow-up six months later. The cost of Group C was relatively higher. (3) In Group C, 66% of the ASC-US patients with HPV-DNA (+) were aged > or = 30. The percentage of histological diagnosis > or = CIN2 was 5.69% in those aged > or = 30 and was 1.22% in those aged < 30. CONCLUSION: Both protocols B and C are practical for clinical management of ASC-US in China. HPV infection is the necessary cause of cervical carcinoma, so the protocol C (cytology and HC-II test) is better for cervical lesion screening. The ASC-US patients aged > or = 30 and with HPV-DNA (+) are at high risk.

Adult↗

PubMed2006

2-methoxyestradiol reduces cerebral vasospasm after 48 hours of experimental subarachnoid hemorrhage in rats.

2-Methoxyestradiol (2ME2), a naturally occurring metabolite of estradiol, is known to have antiproliferative, antiangiogenic, and antiproapoptotic activities. Mechanistically, 2ME2 has been shown to downregulate hypoxia-inducible factor 1alpha (HIF-1alpha). We hypothesized that hypoxia in the major cerebral arteries might activate a unique signaling pathway, hypoxia-inducible factor-1alpha (HIF-1alpha), to produce or enhance cerebral vasospasm after subarachnoid hemorrhage (SAH). Sprague-Dawley male rats (n = 70) were randomly divided into 5 groups: Sham operated, SAH without treatment, SAH treated with vehicle (DMSO), SAH treated with two HIF-1alpha inhibitors, 2ME2, and D609 (positive control of 2ME2). SAH model was produced by middle cerebral artery perforation. 2ME2 and D609 were administered intraperitoneal at 1 h after SAH; rats were sacrificed after 48 h of SAH. Thick blood clot was observed around basilar artery under arachnoids in all animals except Sham group; severe morphological vasospasm was observed in basilar arteries in SAH and SAH+DMSO rats, and the mild vasospasm in rats treated with 2ME2 and D609; 2ME2 and D609 reduced the activity of HIF-1alpha in the basilar arteries by HIF-1alpha DuoSet ELISA; reduce the expression of HIF-1alpha, VEGF, BNIP3 and PCNA in basilar arteries by Western blotting and immunohistochemical staining. In addition, it decreased the mortality and improved the neurological deficits. In conclusion, 2ME2 is a powerful agent to reduce cerebral vasospasm by inhibiting HIF-1alpha activity and the expression of VEGF as its downstream, suppressing endothelium and VSMCs apoptosis via BNIP3 pathway, and attenuating vasoproliferation.

2-Methoxyestradiol↗

PubMed2006

Early responses of osteoblast-like cells to different mechanical signals through various signaling pathways.

This study was to examine the effects of mechanical stimuli alone and coupled with some inhibitors of related signaling pathways on early cellular responses. MG-63 cells were subjected to cyclic uniaxial compressive or tensile strain at 4000 microstrain, produced by four-point bending system. The effects of mechanical strains alone and coupled with inhibitors of microfilament and receptor tyrosine kinase (RTK) on activation of extracellular signal-regulated kinase (ERK), c-fos mRNA, and c-Fos protein were examined. ERK could be activated by mechanical stimuli in 5 min and so could be c-fos mRNA and c-Fos protein in 30 min. Tensile stress had a more obvious effect than compressive one. Early cellular responses were connected with cytoskeleton and RTK pathways during the transduction of mechanical signals. The property of strains was an influential factor for the activation effects.

Cell Line, Tumor↗

PubMed2006

Electron tomography of swollen rigor fibers of insect flight muscle reveals a short and variably angled S2 domain.

Subfragment 2 (S2), the segment that links the two myosin heads to the thick filament backbone, may serve as a swing-out adapter allowing crossbridge access to actin, as the elastic component of crossbridges and as part of a phosphorylation-regulated on-off switch for crossbridges in smooth muscle. Low-salt expansion increases interfilament spacing (from 52 nm to 67 nm) of rigor insect flight muscle fibers and exposes a tethering segment of S2 in many crossbridges. Docking an actoS1 atomic model into EM tomograms of swollen rigor fibers identifies in situ for the first time the location, length and angle assignable to a segment of S2. Correspondence analysis of 1831 38.7 nm crossbridge repeats grouped self-similar forms from which class averages could be computed. The full range of the variability in angles and lengths of exposed S2 was displayed by using class averages for atomic fittings of acto-S1, while S2 was modeled by fitting a length of coiled-coil to unaveraged individual repeats. This hybrid modeling shows that the average length of S2 tethers along the thick filament (except near the tapered ends) is approximately 10 nm, or 16% of S2's total length, with an angular range encompassing 90 degrees axially and 120 degrees azimuthally. The large range of S2 angles indicates that some rigor bridges produce positive force that must be balanced by others producing drag force. The short tethering segment clarifies constraints on the function of S2 in accommodating variable myosin head access to actin. We suggest that the short length of S2 may also favor intermolecular head-head interactions in IFM relaxed thick filaments.

Animals↗

PubMed2006

An unusual Zn-finger/FH2 domain protein controls a left/right asymmetric neuronal fate decision in C. elegans.

Gene regulatory networks that control the terminally differentiated state of a cell are, by and large, only superficially understood. In a mutant screen aimed at identifying regulators of gene batteries that define the differentiated state of two left/right asymmetric C. elegans gustatory neurons, ASEL and ASER, we have isolated a mutant, fozi-1, with a novel mixed-fate phenotype, characterized by de-repression of ASEL fate in ASER. fozi-1 codes for a protein that functions in the nucleus of ASER to inhibit the expression of the LIM homeobox gene lim-6, neuropeptide-encoding genes and putative chemoreceptors of the GCY gene family. The FOZI-1 protein displays a highly unusual domain architecture, that combines two functionally essential C2H2 zinc-finger domains, which are probably involved in transcriptional regulation, with a formin homology 2 (FH2) domain, normally found only in cytosolic regulators of the actin cytoskeleton. We demonstrate that the FH2 domain of FOZI-1 has lost its actin polymerization function but maintains its phylogenetically ancient ability to homodimerize. fozi-1 genetically interacts with several transcription factors and micro RNAs in the context of specific regulatory network motifs. These network motifs endow the system with properties that provide insights into how cells adopt their stable terminally differentiated states.

Alleles↗