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Biomedical subjects

J Xiong

Publications and source records attributed to J Xiong.

At least 19 recordsLinked to original sources

Natural biflavones as novel inhibitors of cathepsin B and K.

Cathepsin B and K, two important members in lysosomal proteases, involve in many serious human diseases, such as tumor and osteoporosis. In order to find their novel inhibitors, we performed the inhibition assays of cathepsin B and cathepsin K in vitro, randomly screened compounds from plants, and found six biflavones, named AMF1-5 and HIF, can potently inhibit cathepsin B and cathepsin K, especially AMF4 and HIF with IC(50) of 0.62 and 0.58 microM against cathepsin B. They are novel inhibitors for cathepsin B and K. Inhibition and flexible docking studies indicated that these biflavones are reversible inhibitors of cathepsin B, and their binding patterns and interaction modes with cathepsin B made them more specific to cathepsin B endopeptidase.

Cathepsin B↗

Dissemination of CTX-M type beta-lactamases in Enterobacteriaceae isolates in the People's Republic of China.

Previously there have been a number of reports of extended spectrum beta-lactamase (ESBL) producing isolates of the family Enterobacteriaceae in Asia. We first reported the occurrence of bla(CTX-M) in Guangzhou, China, subsequently there have been reports of bla(CTX-M) from a number of other south Asian countries. Initial surveillance study data suggested that bla(CTX-M) might be widely distributed in China. This study examines the type of bla(CTX-M) occurring in other major population centres in China. Initial disk diffusion method susceptibility testing (NCCLS) selected ESBL producing Escherichia coli and Klebsiella pneumoniae isolates from Beijing and near Wuhan, PRC. After screening in both China and the UK, 13 isolates producing CTX-M ESBLs were identified and studied, 11 also produced TEM-1, and 4 also produced SHV-1. Sequence analysis of the bla(CTX-M) containing isolates revealed these isolates contained two different bla(CTX-M), three with bla(CTX-M-3) and 10 with bla(CTX-M-14). After comparison with other previously published studies in the English language, we conclude that the most prevalent bla(CTX-M) so far reported in Asia are bla(CTX-M-14) and bla(CTX-M-3).

Anti-Bacterial Agents↗

Metabolic substrates of neuronal aging.

One mechanism proposed to explain age-dependent changes has been the "Ca(2+) hypothesis" of aging. Data indicate that most changes in the Ca(2+) homeostasis of the cerebellar granule neurons appear only when the aged neurons are exposed to higher levels of stimulation and that these changes are secondary to metabolic limitations imposed by altered mitochondrial function.

Aging↗

Description and clinical treatment of an early outbreak of severe acute respiratory syndrome (SARS) in Guangzhou, PR China.

Severe acute respiratory syndrome (SARS), now known to be caused by a coronavirus, probably originated in Guangdong province in southern China in late 2002. The first major outbreak occurred in Guangzhou, the capital of Guangdong, between January and March 2003. This study reviews the clinical presentation, laboratory findings and response to four different treatment protocols. Case notes and laboratory findings were analysed and outcome measures were collected prospectively. The SARS outbreak in Guangdong province and the outbreak in Guangzhou associated with hospitals in the city are described, documenting clinical and laboratory features in a cohort of 190 patients randomly allocated to four treatment regimens. Patients were infected by close contact in either family or health-care settings, particularly following procedures likely to generate aerosols of respiratory secretions (e.g. administration of nebulized drugs and bronchoscopy). The earliest symptom was a high fever followed, in most patients, by dyspnoea, cough and myalgia, with 24 % of patients complaining of diarrhoea. The most frequent chest X-ray changes were patchy consolidation with progression to bilateral bronchopneumonia over 5-10 days. Thirty-six cases developed adult respiratory distress syndrome (ARDS), of whom 11 died. There was no response to antibiotics. The best response (no deaths) was seen in the group of 60 patients receiving early high-dose steroids and nasal CPAP (continuous airway positive pressure) ventilation; the other three treatment groups had significant mortality. Cross-infection to medical and nursing staff was completely prevented in one hospital by rigid adherence to barrier precautions during contact with infected patients. The use of rapid case identification and quarantine has controlled the outbreak in Guangzhou, in which more than 350 patients have been infected. Early administration of high-dose steroids and CPAP ventilation appears to offer the best supportive treatment with a reduced mortality compared with other treatment regimens.

Adult↗

Disruption of BRCA1 LXCXE motif alters BRCA1 functional activity and regulation of RB family but not RB protein binding.

The tumor suppressor activity of the BRCA1 gene product is due, in part, to functional interactions with other tumor suppressors, including p53 and the retinoblastoma (RB) protein. RB binding sites on BRCA1 were identified in the C-terminal BRCT domain (Yarden and Brody, 1999) and in the N-terminus (aa 304-394) (Aprelikova et al., 1999). The N-terminal site contains a consensus RB binding motif, LXCXE (aa 358-362), but the role of this motif in RB binding and BRCA1 functional activity is unclear. In both in vitro and in vivo assays, we found that the BRCA1:RB interaction does not require the BRCA1 LXCXE motif, nor does it require an intact A/B binding pocket of RB. In addition, nuclear co-localization of the endogenous BRCA1 and RB proteins was observed. Over-expression of wild-type BRCA1 (wtBRCA1) did not cause cell cycle arrest but did cause down-regulation of expression of RB, p107, p130, and other proteins (e.g., p300), associated with increased sensitivity to DNA-damaging agents. In contrast, expression of a full-length BRCA1 with an LXCXE inactivating mutation (LXCXE-->RXRXH) failed to down-regulate RB, blocked the down-regulation of RB by wtBRCA1, induced chemoresistance, and abrogated the ability of BRCA1 to mediate tumor growth suppression of DU-145 prostate cancer cells. wtBRCA1-induced chemosensitivity was partially reversed by expression of either Rb or p300 and fully reversed by co-expression of Rb plus p300. Our findings suggest that: (1) disruption of the LXCXE motif within the N-terminal RB binding region alters the biologic function of BRCA1; and (2) over-expression of BRCA1 inhibits the expression of RB and RB family (p107 and p130) proteins.

Amino Acid Motifs↗

[Protective effect of epidural cooling upon ischemic spinal cord injury].

OBJECTIVE: To evaluate the protective effect of epidural cooling on ischemic spinal cord injury. METHODS: Fourteen healthy hybrid dogs were randomly divided into two groups: control group (n = 8) and experimental group (n = 6). Spinal cord injury was induced by double aortic cross-clamping for 40 minutes. Before the clamping, the cerebrospinal fluid temperature of the animals in experimental group was decreased to 30 degrees C +/- 1 degrees C by epidural cooling until the aorta was unclamped for 5 minutes. Three days after the operation, the function of the hind limbs of the animals was evaluated by Tarlov's scale and histological examination of the spinal cord was made. RESULTS: Six dogs showed complete paraplegia (grade 0) and two showed paresis (grade 1) in the control group. The neurological outcome of the experimental group was much better than that in the control group (H = 10.68, P = 0.001). The neurological function of 4 dogs in the experimental group was in grade 4, and one in grade 3. Histological examination revealed hemorrhage of gray matter, degeneration and necrosis of neurons, and severe demyelination of myelinated nerve fibers in the spinal cord from T10 to sacral segments in dogs with paraplegia. The changes in spinal cord were slight in the dogs without severe neurological injury. CONCLUSION: Local hypothermia of spinal cord by epidural cooling provides effective protection against ischemic spinal cord injury in dog.

Animals↗

Occurrence of a new metallo-beta-lactamase IMP-4 carried on a conjugative plasmid in Citrobacter youngae from the People's Republic of China.

During the course of an antimicrobial resistance surveillance programme in Guangzhou, the People's Republic of China, single strains of Citrobacter youngae and Pseudomonas aeruginosa were identified which were resistant to imipenem and found to carry the carbapenemase gene bla(IMP). PCR screening of the citrobacter strain with specific primers for the bla(IMP) type genes gave a 587-bp product which when sequenced gave 100% homology with the bla(IMP-4) sequence reported recently from Acinetobacter spp. The determinant in the C. youngae strain was found to be located on a 156-kb plasmid capable of transfer to Escherichia coli UB1637 by conjugation. Sequencing of the bla(IMP-4) open reading frame in the C. youngae strain and adjacent sequences not only confirmed the presence of bla(IMP-4) but also identified that a conserved core site found within the 59-bp element of integrons was present and the same as the one described in the only other occurrence of bla(IMP-4) in Acinetobacter spp. isolated from an intensive care unit in Hong Kong. This is the second report of transferable carbapenemase genes in Enterobacteriaciae outside of Japan and the first in the People's Republic of China. Under the selective pressure of carbapenems and extended spectrum cephalosporins use we might expect this gene to spread and widespread surveillance should be instituted.

Adult↗

Determination of arsenic species by capillary zone electrophoresis with large-volume field-amplified stacking injection.

Determination of arsenic species by large-volume field amplified stacking injection-capillary zone electrophoresis (LV-FASI-CZE) is reported in this paper. Whole column injection was employed. The optimum buffer pH for the separation of weak acids was discussed. It was found that the optimum buffer to analyze the stacked arsenate (As(V)), monomethylarsonate (MMA), and dimethylarsinate (DMA) was 25 mM phosphate at pH 6.5. However, the optimum buffer to analyze the concentrated arsenite (As(III)) was 20 mM phosphate - 10 mM borate at pH 9.28. The limits of detection of the method developed were 0.026 mg/L for As(III), 0.023 mg/L for As(V), 0.043 mg/L for MMA, and 0.018 mg/L for DMA. An enrichment factor of 34-100 for several arsenic species was obtained. In the end, this method was applied to determine the arsenic concentration in the environmental reference materials to show the usefulness of the method developed.

Arsenates↗

Tagged Transcriptome Display (TTD) in indica rice using Ac transposition.

We have developed a population of transgenic indica rice lines containing the autonomous Activator transposon (Ac) from maize. A transposon excision assay using as the reporter the green fluorescent protein (GFP) gene driven by the ubiquitin promoter was used to monitor Ac excision in various tissues. Our results, based on Ac excision and re-insertion events in 289 independent rice transformants, provide an insight into transposon biology in this heterologous model cereal system. Twenty percent of the transformed calli displayed uniform GFP activity, indicating very early Ac excision, while later excision in another 40% of calli was revealed by mosaic GFP activity. Both phenotypes were confirmed by molecular analysis. Progeny analysis revealed active transposition, with some lines displaying transposition to unlinked positions. Amplification of the Ac copy number was observed in approximately 30% of the lines, thus tagging multiple sites. We developed a "transposon insertion display" procedure, involving the use of CpG methylation-sensitive enzymes and a macroarray-based approach with cDNA as a complex hybridization probe, to selectively detect transposon insertions in transcribed sequences. Sequencing of tagged sites identified by hybridization to leaf cDNA revealed that all the hybridizing tags were homologous to genes or ESTs present in databases. Extrapolation from these data suggests that 12% of all amplified tags display homology to genes or ESTs - five times more than would be expected on the basis of random transpositional insertion. This Tagged Transcriptome Display (TTD) technique, using a population of Ac insertion-tagged lines, therefore represents a convenient approach for the identification of tagged genes involved in specific processes, as revealed by their expression patterns.

Base Sequence↗

Cerebral hemodynamic response in Chinese (first) and English (second) language processing revealed by event-related functional MRI.

Comparative functional neuroimaging studies using the block design paradigm have previously demonstrated that there are no significant differences in the location of areas of cerebral activation when native Chinese speakers independently process single words or sentences in both the Chinese (first) and English (second) languages. While it has also been documented that significant domains of brain response include the inferior to middle left frontal lobe, the latency, amplitude and duration of the associated hemodynamic changes during isolated neural processing of Chinese and English languages still remain unknown. The aim of this study, therefore, was to examine the characteristics of the hemodynamic alterations in the above-mentioned regions with event-related functional MRI (ER-fMRI) when native Chinese speakers performed verb generation tasks in both the Chinese (first) and English (second) languages. Our results demonstrate the presence of a similar neural activity-induced hemodynamic response in the inferior to middle left frontal lobe during both tasks. Further, there were also no statistically significant differences among the variables that described the hemodynamic response curves. These findings strongly imply that the underlying neural mechanism for Chinese (first) and English (second) language processing may be similar in native Chinese speakers.

Adult↗

[Generation of Mx-cre transgenic mice].

To generate the transgenic mice expressing cyclization recombination enzyme, the recombinant gene, in which the coding region of cre gene is derived by the promoter of mouse Mx gene, was microinjected into pronuclei of fertilized mouse eggs. Founders of transgenic mice harbouring the recombinant gene were screened by polymerase chain reaction (PCR) at genomic DNA level and confirmed by Southern blot. One line of Mx-cre transgenic mice was obtained. Then, the Mx-cre transgenic mouse line was cultured and propagated.

Animals↗

Amygdalar and hippocampal volumetry in control participants: differences regarding handedness.

BACKGROUND AND PURPOSE: Amygdalar and hippocampal volume measurements indicate a right-greater-than-left asymmetry for right-handed normal participants in most studies. The purpose of this study was to compare amygdalar and hippocampal volume ratios between right- and left-handed participants. METHODS: Amygdalar and hippocampal volume measurements were performed in 34 (20 right-handed and 14 left-handed) normal participants. All participants completed a 10-item handedness questionnaire. The MR imaging sequence was a 3D T1-weighted gradient-echo acquisition of the whole brain (24/6 [TR/TE]; flip angle, 25 degrees). MR images were spatially normalized, and volumes were painted with a 1.0-mm(3) resolution cursor on an SGI workstation. RESULTS: In right-handed participants, the amygdala and hippocampus (P <.001 for both) were significantly larger on the right side than on the left. The left-handed group did not show a significant difference between right- and left-sided structures. Right-to-left volume ratios differed significantly between right- and left-handed participants for both amygdalar (P <.02) and hippocampal (P <.01) structures. Gender did not affect right-to-left amygdalar and hippocampal volume ratios in right- or left-handed participants. CONCLUSION: Handedness, but not gender, seems to affect right-to-left amygdalar and hippocampal volume ratios.

Adult↗

[Detection of Cre recombinase activity in Mx-Cre transgenic mice induced by INF in vitro].

The Cre recombinase and its activity in C57-TgN(Mx-Cre) transgenic mice is studied by polymerase chain reaction (PCR), Western blot, immunohistochemistry, immunogold electron microscopy and Southern blot. C57-TgN(Mx-Cre) transgenic mice harbouring cre gene in genomic DNA is demonstrated by PCR, and these mice which are induced by INF-alpha 1b could express Cre recombinase, which is confirmed by Western blot. With immunohistochemistry, we find that the Cre recombinase expresses in hepatocyte cytoplasm and nuclear of C57-TgN(Mx-Cre) transgenic mice. Cre recombinase expressed in hepatocyte cytoplasm and nuclear is further confirmed by immunogold electon microscopy. And it is supported that the Cre recombinase which is created from C57-TgN(Mx-Cre) transgenic mice induced by INF-alpha 1b can direct DNA recombination reaction in vitro. All evidence leads us supporting the view that the Cre recombinase expressed in C57-TgN(Mx-Cre) transgenic mice has activity. Thus we find a method to detect the activity of Cre recombinase in vitro.

Animals↗

[The presentation of neo gene in chimeric mice obtained from ES cells].

To explore the potentiality of the mouse ES cell line which is employed in our laboratory were transfected with neo gene and selected with G418. Some ES cell clones expressing neo gene were obtained. After ES clones were picked up and expanded, the ES cells were mircoinjected into blastocysts and implanted miceuterus. 60 blastocysts were implanted into 5 mice. Finally, 3 chimeric mice with neo gene were born. PCR was carried out to analyze the presentation of neo gene in tissues of chimeric mice. The results showed that many tissues harbored the neo gene, including skin, liver and blood et al.

Animals↗

[Expression of cell cycle associated proteins cyclin D1 and P16 in endometrial carcinoma and the correlation between their expression status].

OBJECTIVE: To study the expression of cell cycle associated proteins Cyclin D1, P16 in endometrial carcinoma and their correlation to clinical parameters, and to assess the correlation between their expression status. METHODS: Immunohistochemical method was used to detect Cyclin D1 and P16 expressions in 64 cases of endometrial carcinoma. RESULT: The positive rate of Cyclin D1 was 54.68%. The Cyclin D1 expression was significantly associated with FIGO stage (P < 0.05). The positive rate of P16 was 53.13% and its expression was related to age, histological grade and FIGO stage (P < 0.05). There was an inverse correlation between Cyclin D1 and P16, r = -0.4007 (P < 0.01). CONCLUSION: Cyclin D1 and P16 had cooperative effect and may play an important role in the development and progression of endometrial carcinoma.

Adenocarcinoma↗

Molecular evidence for the early evolution of photosynthesis.

The origin and evolution of photosynthesis have long remained enigmatic due to a lack of sequence information of photosynthesis genes across the entire photosynthetic domain. To probe early evolutionary history of photosynthesis, we obtained new sequence information of a number of photosynthesis genes from the green sulfur bacterium Chlorobium tepidum and the green nonsulfur bacterium Chloroflexus aurantiacus. A total of 31 open reading frames that encode enzymes involved in bacteriochlorophyll/porphyrin biosynthesis, carotenoid biosynthesis, and photosynthetic electron transfer were identified in about 100 kilobase pairs of genomic sequence. Phylogenetic analyses of multiple magnesium-tetrapyrrole biosynthesis genes using a combination of distance, maximum parsimony, and maximum likelihood methods indicate that heliobacteria are closest to the last common ancestor of all oxygenic photosynthetic lineages and that green sulfur bacteria and green nonsulfur bacteria are each other's closest relatives. Parsimony and distance analyses further identify purple bacteria as the earliest emerging photosynthetic lineage. These results challenge previous conclusions based on 16S ribosomal RNA and Hsp60/Hsp70 analyses that green nonsulfur bacteria or heliobacteria are the earliest phototrophs. The overall consensus of our phylogenetic analysis, that bacteriochlorophyll biosynthesis evolved before chlorophyll biosynthesis, also argues against the long-held Granick hypothesis.

Bacteria↗

The O(2) binding pocket of myohemerythrin: role of a conserved leucine.

A conserved O(2) binding pocket residue in Phascolopsis gouldii myohemerythrin (myoHr), namely, L104, was mutated to several other residues, and the effects on O(2) association and dissociation rates, O(2) affinity, and autoxidation were examined. The L104V, -F, and -Y myoHrs formed stable O(2) adducts whose UV-vis and resonance Raman spectra closely matched those of wild-type oxymyoHr. The L104V mutation produced only minimal effects on either O(2) association or dissociation, whereas the L104F and -Y mutations resulted in 100-300-fold decreases in both O(2) association and dissociation rates. These decreases are attributed to introduction of steric restrictions into the O(2) binding pocket, which are not present in either wild-type or L104V myoHrs. The failure to observe increased O(2) association or dissociation rates for L104V indicates that the side chain of leucine at position 104 does not sterically "gate" O(2) entry into or exit from the binding pocket in the rate-determining step(s). L104V myoHr autoxidized approximately 3 times faster than did wild type, whereas L104T autoxidized >10(6) times faster than did wild type. The latter large increase is attributed to increased side chain polarity, thereby increasing water occupancy in the oxymyoHr binding pocket. These results indicate that L104 contributes a hydrophobic barrier that restricts water entry into the oxymyoHr binding pocket. Thus, a leucine at position 104 in myoHr appears to have the optimal combination of size and hydrophobicity to facilitate O(2) binding while simultaneously inhibiting autoxidation.

Amino Acid Sequence↗

A hemerythrin-like domain in a bacterial chemotaxis protein.

Hemerythrin (Hr) is an O(2)-carrying protein found in some marine invertebrates. A conserved sequence motif in all Hrs provides five histidine and two carboxylate ligands to an oxo-/hydroxo-bridged diiron active site, as well as a hydrophobic O(2) binding pocket. Database searches located a previously unrecognized Hr-like sequence motif at the 3' end of the gene, dcrH, from the anaerobic sulfate-reducing bacterium, Desulfovibrio (D.) vulgaris (Hildenborough). This gene encodes a putative methyl-accepting chemotaxis protein, DcrH. We have established by immunoblotting that a full-length DcrH, including the Hr-like domain, is expressed in D. vulgaris (Hildenborough). The C-terminal domain of DcrH, when expressed separately in recombinant form in Escherichia coli, was found to fold into a stable protein, DcrH-Hr. The UV-vis absorption and resonance Raman spectra of DcrH-Hr, and of its azide adduct, provide clear evidence for an oxo-bridged diiron(III) site very similar to that found in Hr. Based on UV-vis absorption spectra, exposure of the reduced (colorless, presumably diferrous) DcrH-Hr to air resulted in formation of an O(2) adduct also very similar to that of Hr. Unlike that of Hr, the O(2) adduct of DcrH-Hr autoxidized within a few minutes at room temperature. The O(2) binding pocket of DcrH-Hr appears to be larger than that of Hr. Given the air-sensitive nature of D. vulgaris and the putative chemotactic function of DcrH, one possible role for the Hr-like domain of DcrH is O(2)-sensing. DcrH-Hr is the first characterized example of a Hr-like protein from any microorganism.

Amino Acid Sequence↗