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Biomedical subjects

Li Zhang

Publications and source records attributed to Li Zhang.

At least 577 records · Page 32Linked to original sources

[Na+/dicarboxylate cotransporter expression changed with aging in basolateral membrane of the renal tubular epithelial cells].

OBJECTIVE: To study the change with aging of Na(+)/dicarboxylate cotransporter (NaDC3) expression in basolateral membrane of epithelial cell in proximal renal tubules in rat and human being. METHODS: Six groups of 6 Wistar rats at the age of: 1 day, 7 days, 1 month, 3 months, 12 months, and 24 months respectively were killed and their kidneys were taken to be examined immunohistochemically. Samples of kidney from 15 normal human beings, 5 in the group aged 6 - 8, 5 in the group aged 32 - 44, and 5 in the group aged 63 - 65, were examined immunohistochemically. Northern blotting, and Western blotting were used to detect the mRNA and protein expression of NaDC3 in renal tissues from both rats and human beings. The concentrations of citrate in both plasma and urine of the rats were tested. RESULTS: (1) The concentration of citrate in urine was340 mg/L +/- 144 mg/L in rats at the age of 7 days and declined gradually with aging significantly to the value of 59 mg/L +/- 27 mg/L in the rats aged 24 months (P < 0.05). The concentration of citrate in rat plasma was 85 mg/L +/- 45 mg/L and then declined gradually with aging significantly to the value of 31 mg/L +/- 20 mg/L at the age of 24 months (P < 0.05). (2) The renal expression of both mRNA and protein of NaDC3 increased with aging in rats and human beings (P < 0.01). (3) Located in the basolateral membrane of epithelial cell in the proximal renal tubule, NaDC3 expression began to be detected in rat since at the age of 7 days and then increased gradually in comparison with that at the day 7 (P < 0.01). However, the value of NaDC3 expression at the age of 24 months was not significantly different from that at the age of 12 months (P > 0.05). Similar results were also observed in normal human beings. CONCLUSION: NaDC3 may play a role in the aging process through the metabolic mechanism of citrate, etc.

Adult↗

Magnetic resonance imaging and neurosphere therapy of stroke in rat.

We intracisternally transplanted subventricular zone (SVZ) cells labeled by ferromagnetic particles into stroked rats. Migration of transplanted cells was non-invasively tracked using magnetic resonance imaging (MRI). We found that transplanted cells selectively migrated towards the ischemic parenchyma at a mean speed of 65 +/- 14.6 microm/hr in living rats. Migration of transplanted cells in the brain was also measured histopathologically. Rats transplanted with SVZ cells exhibited significant improvement of neurological function. Our data suggest that intracisternal transplantation of SVZ cells provides an avenue for cell therapy of stroke and that MRI can be used to track grafted cells in the brain.

Animals↗

Induction of P450 monooxygenases in the German cockroach, Blattella germanica L.

The cytochrome P450 monooxygenases are an important metabolic system whose level of activity can be influenced by several dietary constituents. We examined the effects of six known P450 inducers on the levels of total cytochromes P450, cytochrome b(5), and six monooxygenase activities in adult German cockroaches. In addition, the levels of CYP6L1 and CYP9E2 mRNA were also investigated. Phenobarbital treatment resulted in increases in total cytochromes P450 and metabolism of three resorufin analogues, but not CYP6L1 nor CYP9E2 mRNA. There was no significant effect of the other five inducers on any of the monooxygenase parameters we measured. In comparison with other insects, the German cockroach seems unusually refractory to most inducing agents.

Acetone↗

Flavonoids: promising anticancer agents.

Flavonoids are polyphenolic compounds that are ubiquitously in plants. They have been shown to possess a variety of biological activities at nontoxic concentrations in organisms. The role of dietary flavonoids in cancer prevention is widely discussed. Compelling data from laboratory studies, epidemiological investigations, and human clinical trials indicate that flavonoids have important effects on cancer chemoprevention and chemotherapy. Many mechanisms of action have been identified, including carcinogen inactivation, antiproliferation, cell cycle arrest, induction of apoptosis and differentiation, inhibition of angiogenesis, antioxidation and reversal of multidrug resistance or a combination of these mechanisms. Based on these results, flavonoids may be promising anticancer agents.

Anticarcinogenic Agents↗

Distribution of variant genotypes of Fc gamma receptor IIIa in healthy Chinese population of Zhengzhou City.

To investigate the distribution of variant genotypes of Fc gamma receptor IIIa (Fc gamma R IIIa) in healthy Chinese population of Zhengzhou city, genomic DNA was extracted from peripheral blood of healthy donators. The genotypes of Fc gamma R IIIa-158 were determined by nested polymerase chain reaction (PCR) in 137 healthy people in Zhengzhou city. The results showed that frequencies of variant genotypes FF, VV and VF were 42.3%, 48.9% and 8.8% respectively. The distribution of Fc gamma R IIIa-158 in healthy Chinese population of Zhengzhou city was polymorphic and different from that of African Americans (AA) and Caucasian Americans (CA).

Asian People↗

Designing metaschemas for the UMLS enriched semantic network.

The enriched semantic network (ESN) has previously been presented as an enhancement of the semantic network (SN) of the UMLS. The ESN's hierarchy is a DAG (Directed Acyclic Graph) structure allowing for multiple parents. The ESN is thus more complex than the SN and can be more difficult to view and comprehend. We have previously introduced the notion of a metaschema for the SN as a compact abstraction to support SN comprehension. We extend the definition of metaschema to make it applicable to a DAG classification hierarchy, such as the one exhibited by the ESN. We specify the requirements for and describe the general process of deriving such a metaschema. We derive two particular metaschemas of the ESN based on a pair of partitions. These two metaschemas and their underlying partitions are compared. Both metaschemas serve as compact representations of the ESN, allowing for convenient viewing of its hierarchy and easier comprehension.

Abstracting and Indexing↗

Application of nano TiO(2) towards polluted water treatment combined with electro-photochemical method.

A novel composite reactor was prepared and studied towards the degradation of organic pollutants in this work. In the reactor, a UV lamp was installed to provide energy to excite nano TiO(2), which served as photocatalyst, leading to the production of hole-electron pairs, and a three-electrode electrolysis system was used to accumulate H(2)O(2) which played an important role in the degradation process. The reactor was evaluated by the degradation process of rhodamine 6G (R-6G), and the data obtained in the experiments showed that the combination of the photochemical and electrochemical system raised the degradation rate of R-6G greatly; the working mechanism of the reactor was also discussed in the article. The prepared reactor was also utilized to treat polluted water from dyeing and printing process. After continuous treatment for 0.5h, chemical oxygen demand biochemical oxygen demand, quantity of bacteria and ammonia nitrogen of the polluted water were reduced by 93.9%, 87.6%, 99.9% and 67.5%, respectively, which indicated that the method used here could be used for effective organic dyes degradation.

Catalysis↗

Dynorphin A inhibits NMDA receptors through a pH-dependent mechanism.

Dynorphin A (DynA), an endogenous agonist of kappa-opioid receptors, has also been reported to directly interact with the NMDA receptor. DynA inhibition of NMDA receptor function has been suggested to be involved in its neuroprotective action during ischemic and acidic conditions. However, the effect of external pH on DynA inhibition of the NMDA receptor has not been reported. Here, we show that DynA inhibition of the NMDA receptor is dependent on extracellular pH over the range of pH 6.7-8.3, and the inhibition by 10 microM DynA increases at low pH by three- to four-fold in hippocampal neurons and in Xenopus oocytes expressing NR1-1a/2B subunits. Molecular studies showed that the interacting site for DynA on the NMDA receptor is distinct from that of proton or redox sites. Peptide mapping demonstrated important contributions of positively charged residues and specific structural organization of the peptide to the potency of DynA inhibition. Thus, DynA inhibits NMDA receptors through an allosteric mechanism, which is pH dependent and involves the specific structural features of the peptide.

Allosteric Regulation↗

Distinct domains of the limbic system-associated membrane protein (LAMP) mediate discrete effects on neurite outgrowth.

The limbic system-associated membrane protein (LAMP) is a glycosylphosphatidylinositol-anchored glycoprotein with three immunoglobulin (Ig) domains that can either enhance or inhibit neurite outgrowth depending upon the neuronal population examined. In the present study, we investigate the domains responsible for these activities. Domain deletion revealed that the N-terminal IgI domain is necessary and sufficient for the neurite-promoting activity observed in hippocampal neurons. In contrast, inhibition of neurite outgrowth in SCG neurons, which is mediated by heterophilic interactions, requires full-length LAMP, although selective inhibition of the second Ig domain, but not the first or third domains, prevented the inhibitory effect. This indicates that the IgII domain of LAMP harbors the neurite-inhibiting activity, but only in the context of the full-length configuration. Covasphere-binding analyses demonstrate IgI/IgI interactions, but no interaction between IgII and any other domain, consistent with the biological activities that each domain mediates. The data suggest that LAMP may serve as a bifunctional guidance molecule, with distinct structural domains contributing to the promotion and inhibition of neurite outgrowth.

Animals↗

Application of the S-score algorithm for analysis of oligonucleotide microarrays.

In the past several years, oligonucleotide microarrays have emerged as a widely used tool for the simultaneous, non-biased measurement of expression levels for thousands of genes. Several challenges exist in successfully utilizing this biotechnology; principal among these is analysis of microarray data. An experiment to measure differential gene expression can consist of a dozen microarrays, each consisting of over a hundred thousand data points. Previously, we have described the use of a novel algorithm for analyzing oligonucleotide microarrays and assessing changes in gene expression. This algorithm describes changes in expression in terms of the statistical significance (S-score) of change, which combines signals detected by multiple probe pairs according to an error model characteristic of oligonucleotide arrays. Software is available that simplifies the use of the application of this algorithm so that it may be applied to improving the analysis of oligonucleotide microarray data. The application of this method to problems of the central nervous system is discussed.

Algorithms↗

Angiostatin production in cultivation of recombinant Pichia pastoris fed with mixed carbon sources.

A recombinant strain of Pichia pastoris with a phenotype of MutS was used to produce angiostatin. Due to the low methanol consumption rate of this strain, both methanol and glycerol feedings, that produced oscillation in dissolved O2 concentration, were used during the expression phase to improve cell growth and angiostatin expression. However, enhanced cell growth led to nitrogen limitation that suppressed further production of angiostatin, but addition of ammonia allowed angiostatin concentration to reach 108 mg l(-1) after an expression period of 96 h. The ratio of consumed glycerol to methanol of 1.5:1 (w/w) in the expression phase suggested that methanol played an important role in the metabolism of carbon sources.

Ammonia↗

Role of Shc in T-cell development and function.

Shc is a prototype adapter protein that is expressed from the earliest stages of T-cell development. Shc becomes rapidly tyrosine phosphorylated after T-cell receptor (TCR) engagement. Expression of dominant negative forms of Shc in T-cell lines had also suggested a role for this adapter downstream of the TCR. However, until recently, the relative significance of Shc compared to several other adapters in T cells was unclear. Mice lacking Shc expression specifically in the T-cell lineage together with inducible expression of dominant negative Shc in transgenic mice have revealed an essential and nonredundant role for Shc in thymic T-cell development. Functional defects in a Jurkat T-cell line lacking Shc expression also suggest a role for Shc in mature T-cell functions. While the requirement of Shc in T-cell signaling is now established, precisely what signaling pathways downstream of Shc make this adapter unique are less clear. Although the Shc-mediated activation of the extracellular signal regulated kinase (Erk)/mitogen-activated protein kinase (MAPK) pathway could be one component, Shc likely signals to other pathways in T cells that are not yet discovered. A better molecular understanding of Shc function in the future could provide insights into how multiple adapters coordinate the various outcomes downstream of the TCR.

Animals↗

Application of traditional Chinese medicine in the treatment of infertility.

The philosophy and practice of traditional Chinese medicine (TCM) have been evolving for thousands of years in China, Japan and other Asian countries. TCM is now generating popular interest worldwide for reproductive health care and disease prevention, including applications for treating infertility and improving sexual function. This review focuses on the application of TCM for infertility patients, and provides a critical reflection on the efficacy and safety of selected Chinese herbal formulas. It has been claimed that some formulas produce high clinical pregnancy rates with few or no side effects, as well as improving the general well-being of patients. The need for randomized control trials and research into possible mechanisms of action, effective doses, contra-indications and toxicity is self-evident. However, the task is enormous in view of the number of herbal products currently available on the market; yet among these products are undoubtedly some that will prove to be safe and beneficial.

Animals↗

Functional genetic selection of the decoding center in E. coli 16S rRNA.

Ribosomal RNAs (rRNAs) play crucial roles in protein biosynthesis. The decoding center of 16S rRNA in 30S subunit affords a place for interaction between mRNA and tRNA, and contributes to the fidelity of the decoding by monitoring the codon-anticodon base pairing. The helices 18 and 44 in 16S rRNA are known to be major components of the decoding center. To investigate functional role of the conserved sequence in rRNAs, we employed a new genetic method that allows us to identify and select from randomized E. coli rRNA libraries those rRNA sequences absolutely required for the ribosome function. Functional consensus sequences were identified in both helices, providing us with a new insight into the decoding mechanism.

Escherichia coli↗

Immediate microcirculatory derangements in skeletal muscle and periosteum after closed tibial fracture.

BACKGROUND: Severe musculoskeletal soft tissue injury sustained after a closed fracture to the extremities significantly influences bone healing and determines the patient's prognosis. The present study was aimed at quantitatively assessing immediate microcirculatory changes in skeletal muscle and periosteum after standardized closed fracture. METHODS: Standardized closed fracture of the left tibia in isoflurane-anesthetized Sprague-Dawley rats (n = 14) was induced using a modified weight-drop technique. The left extensor digitorum longus (EDL) muscle (n = 7) and tibial periosteum (n = 7) were surgically exposed for in vivo fluorescence microscopy 15 minutes after fracture. Nonfractured rats (n = 14) served as controls. EDL muscle edema was determined by the ratio of wet to dry weight (EDL water content). RESULTS: Closed tibial fracture resulted in a significant reduction of functional capillary density, red blood cell velocity, and volumetric blood flow in both EDL muscle and periosteum. Microvascular diameter, leukocyte adherence, and macromolecular leakage were markedly increased, indicating trauma-induced inflammation and endothelial disintegration. EDL muscle edema was found increased significantly after fracture. CONCLUSION: This model permits for the first time direct in vivo visualization and quantification of fracture-induced microhemodynamic changes and cellular interactions within the surrounding soft tissue. It demonstrates that even simple fractures lead to profound microcirculatory disturbances in skeletal muscle and periosteum, and also at sites remote from the diaphyseal fracture site. It provides a useful approach for the development of therapeutic strategies to counteract fracture-induced microvascular dysfunction.

Animals↗

A missense mutation (L166P) in DJ-1, linked to familial Parkinson's disease, confers reduced protein stability and impairs homo-oligomerization.

The identification of genetic mutations responsible for rare familial forms of Parkinson's disease (PD) have provided tremendous insight into the molecular pathogenesis of this disorder. Mutations in the DJ-1 gene cause autosomal recessive early onset PD in two European families. A Dutch kindred displays a large homozygous genomic deletion encompassing exons 1-5 of the DJ-1 gene, whereas an Italian kindred harbors a single homozygous L166P missense mutation. A homozygous M26I missense mutation was also recently reported in an Ashkenazi Jewish patient with early onset PD. Mutations in DJ-1 are predicted to be loss of function. The recent determination of the crystal structure of human DJ-1 demonstrates that it exists in a homo-dimeric form in vitro, whereas the L166P mutant exists only as a monomer. Here, we examine the in vivo effects of the pathogenic L166P and M26I mutations on the properties of DJ-1 in cell culture. We report that the L166P mutation confers markedly reduced protein stability to DJ-1, which results from enhanced degradation by the 20S/26S proteasome but not from a loss of mRNA expression. Furthermore, the L166P mutant protein exhibits an impaired ability to self-interact to form homo-oligomers. In contrast, the M26I mutation does not appear to adversely affect either protein stability, turnover by the proteasome, or the capacity of DJ-1 to form homo-oligomers. These properties of the L166P mutation may contribute to the loss of normal DJ-1 function and are likely to be the underlying cause of early onset PD in affected members of the Italian kindred.

Autoantigens↗

Proopiomelanocortin peptides and sebogenesis.

Previous animal studies have demonstrated that alpha-melanocyte-stimulating hormone (alpha-MSH) is a sebotropic hormone in rats and that targeted disruption of melanocortin 5 receptor (MC5-R) can down-regulate sebum output in mice. To study the role of proopiomelanocortin (POMC) peptides in the regulation of human sebaceous lipid production and sebocyte differentiation, we established a primary human sebocyte culture system. Sebocytes were derived from normal human facial skin. Differentiation of sebocytes, induced by POMC-derived peptides such as MSH, adrenocorticotropic hormone (ACTH), or bovine pituitary extract (BPE), resulted in the appearance of prominent cytoplasmic lipid droplets. Partial induction of sebocyte differentiation also was observed in serum-depleted cultures, but there was very limited spontaneous differentiation in serum-containing medium. Analysis by high-performance thin-layer chromatography (HPTLC) of (14)C-acetate-labeled lipids showed a dose-dependent increase in synthesis of sebaceous-specific lipid (i.e., squalene) induced by NDP alpha-MSH. Molecular studies using RT-PCR showed a low level of human MC5-R expression under serum-free condition but a substantial increase after treatment with NDP alpha-MSH or BPE. In contrast, MC1-R expression remained the same, independent of treatment. Our data indicate that expression of MC5-R correlates with sebocyte differentiation and suggest a regulatory role for MC5-R in human sebaceous lipid production.

Animals↗

Structural environment dictates the biological significance of heme-responsive motifs and the role of Hsp90 in the activation of the heme activator protein Hap1.

Heme-responsive motifs (HRMs) mediate heme regulation of diverse regulatory proteins. The heme activator protein Hap1 contains seven HRMs, but only one of them, HRM7, is essential for heme activation of Hap1. To better understand the molecular basis underlying the biological significance of HRMs, we examined the effects of various mutations of HRM7 on Hap1. We found that diverse mutations of HRM7 significantly diminished the extent of Hap1 activation by heme and moderately enhanced the interaction of Hap1 with Hsp90. Furthermore, deletions of nonregulatory sequences completely abolished heme activation of Hap1 and greatly enhanced the interaction of Hap1 with Hsp90. These results show that the biological functions of HRMs and Hsp90 are highly sensitive to structural changes. The unique role of HRM7 in heme activation stems from its specific structural environment, not its mere presence. Likewise, the role of Hsp90 in Hap1 activation is dictated by the conformational or structural state of Hap1, not by the mere strength of Hap1-Hsp90 interaction. It appears likely that HRM7 and Hsp90 act together to promote the Hap1 conformational changes that are necessary for Hap1 activation. Such fundamental mechanisms of HRM-Hsp90 cooperation may operate in diverse regulatory systems to mediate signal transduction.

Amino Acid Motifs↗