Biomedical subjects

Ping Wei

Publications and source records attributed to Ping Wei.

At least 19 recordsLinked to original sources

PubMed2026

Genetic and pathogenic characterization of a novel infectious bursal disease virus field strain with natural reassortant and recombinant features from southern China.

NN040124 is a novel field-derived IBDV strain (vv-A/att-B) exhibiting both reassortment and recombination events.Infection with NN040124 causes 40% mortality and severe lymphoid depletion in three-yellow chickens.These findings demonstrate the pivotal role of the N-terminal domain of segment B in IBDV pathogenicity and virulence.

A3B1a↗

PubMed2025

Effective detection of 148 cases chromosomal mosaicism by karyotyping, chromosomal microarray analysis and QF-PCR in 32,967 prenatal diagnoses.

BACKGROUND: Detection of mosaicism has always been difficult in prenatal diagnosis, which is to assess the value of karyotyping combined with three different molecular genetic tests for prenatal diagnosis. Retrospective review of chromosomal mosaicism (CM) was conducted in 32,967 pregnant women from January 2015 to December 2022. METHODS: A total of 148 fetuses diagnosed with chromosomal mosaicism by karyotyping with copy number variant sequencing (CNV-seq)/ chromosomal microarray analysis (CMA) and quantitative fluorescent polymerase chain reaction (QF-PCR) were selected, and the results from three the methods were compared and further analyzed. The χ2 test for multiple group rates was for the 5 clinical prenatal diagnostic indication groups was used to do multiple comparison tests for statistical analysis. Inconsistent results between methods were identified and further analyzed. RESULTS: A total of 148 CM cases was detected (0.45%, 148/32967), of which karyotyping was detected in combination with CMA in 73 cases (73/85), with CNV-seq in 5 cases (5/11), and with QF-PCR in 35 cases (35/52) and the mosaic conformity rates of the three methods compared with karyotyping were 85.9% (CMA), 67.3% (QF-PCR), and 45.5% (CNV-seq), respectively. There were 49 cases of autosomal mosaicism (49/148, 33.1%) and 99 cases of sex CM (99/148, 66.9%). There were 9 cases of small supernumerary marker chromosome (sSMC)with CMA detection clarified the origin of chromosome fragments. The non-invasive prenatal testing (NIPT) group and the ultrasound abnormality group had the highest detection rates, accounting for 35.1% and 22.3%. CONCLUSIONS: In chromosomal mosaicism, there are inconsistent results between different detection methods. Therefore, karyotyping combined with CMA/CNV-seq and FISH methods significantly improves the detection rate of chromosomal mosaicism and also confirms experimental data in the literature, which is of great value for prenatal diagnosis.

Humans↗

PubMed2006

Combined antioxidant effects of rutin and vitamin C in Triton X-100 micelles.

UV-vis spectra, fluorescence emission spectra and cyclic voltammetric measurements were used to study the influence of Vitamin C on the antioxidant of rutin in Triton X-100 micelles. Rutin can be located in Triton X-100 micelles spontaneously through hydrophobic force, and the binding constant K between rutin and Triton X-100 increases with the rutin concentration. The embedment of two hydroxyl groups on rutin into the more hydrophobic micellar microenvironment makes the oxidation of rutin harder and the radical scavenging activity decrease. With low concentration of Vitamin C, the antioxidant capacity of rutin against hydroxyl radical is enhanced, while that capacity is partly inhibited when the concentration of Vitamin C become higher.

Antioxidants↗

PubMed2006

Mechanisms of genotoxin-induced transcription and hypermutation in p53.

It is widely assumed that genotoxin-induced damage (e.g., G-to-T transversions) to the tumor suppressor gene, p53, is a direct cause of cancer. However, genotoxins also induce the stress response, which upregulates p53 transcription and the formation of secondary structures from ssDNA. Since unpaired bases are thermodynamically unstable and intrinsically mutable, increased transcription could be the cause of hypermutation, and thus cancer. Support for this hypothesis has been obtained by analyzing 6662 mutations in all types of cancer compared to lung and colon cancers, using the p53 mutation database. The data suggest that genotoxins have two independent effects: first, they induce p53 transcription, which increases the number of mutable bases that determine the incidence of cancer. Second, genotoxins may alter the fate, or ultimate mutation of a mutable base, for example, by causing more of the available mutable Gs to mutate to T, leaving fewer to mutate to A. Such effects on the fate of mutable bases have no impact on the incidence of cancer, as both types of mutations lead to cancer.

Journal Article↗

PubMed2006

Enzymatic synthesis of (R)-cyanohydrins by a novel (R)-oxynitrilase from Vicia sativa L.

The defatted seed meal of common vetch (Vicia sativa L.) served as a source of (R)-oxynitrilase which catalyzed the enantioselective addition of HCN to aromatic, heteroaromatic, fluoro-substituted aromatic aldehydes to produce the corresponding enantiomeric pure cyanohydrins in yields of 52-100% and 88-99% ee at 12 degrees C under micro-aqueous medium (diisopropyl ether) without addition of buffer solution.

Aldehyde-Lyases↗

PubMed2006

A protective role for keratinocyte growth factor in a murine model of chemotherapy and radiotherapy-induced mucositis.

PURPOSE: To evaluate the activity of palifermin (rHuKGF) in a murine model of mucosal damage induced by a radiotherapy/chemotherapy (RT/CT) regimen mimicking treatment protocols used in head-and-neck cancer patients. METHODS AND MATERIALS: A model of mucosal damage induced by RT/CT was established by injecting female BDF1 mice with cisplatin (10 mg/kg) on Day 1; 5-fluorouracil (40 mg/kg/day) on Days 1-4, and irradiation (5 Gy/day) to the head and neck on Days 1-5. Palifermin was administered subcutaneously on Days -2 to 0 (5 mg/kg/day) and on Day 5 (5 mg/kg). Evaluations included body weight, organ weight, keratinocyte growth factor receptor expression, epithelial thickness, and cellular proliferation. RESULTS: Initiation of the radiochemotherapeutic regimen resulted in a reduction in body weight in control animals. Palifermin administration suppressed weight loss and resulted in increased organ weight (salivary glands and small intestine), epithelial thickness (esophagus and tongue), and cellular proliferation (tongue and salivary glands). CONCLUSIONS: Administration of palifermin before RT/CT promotes cell proliferation and increases in epithelial thickness in the oral mucosa, salivary glands, and digestive tract. Palifermin administration before and after RT/CT mitigates weight loss and a trophic effect on the intestinal mucosa and salivary glands, suggesting that palifermin use should be investigated further in the RT/CT settings, in which intestinal mucositis and salivary gland dysfunction are predominant side effects of cytotoxic therapy.

Animals↗

PubMed2006

Processing multidimensional objects under different perceptual loads: the priority of bottom-up perceptual saliency.

The role of perceptual load in selective attention to multidimensional objects was investigated by independently manipulating the load along the task-relevant and the task-irrelevant dimensions in the central search array, which was flanked by congruent, incongruent, or neutral peripheral distractors. The relative bottom-up perceptual saliency of these dimensions in capturing attention was manipulated between experiments. When the task-relevant dimension was the color of the letter and the task-irrelevant dimension was the visual shape of the letter (Experiment 1), manipulation of the letter shape perceptual load had no impact upon the pattern of congruency effects in responding to the color, i.e., smaller congruency effects under higher color perceptual loads and larger congruency effects under lower color perceptual loads. When the task-relevant dimension was the shape of the letter and the task-irrelevant dimension was the color of the letter (Experiment 2), there were no congruency effects in responding to the letter shape under high color perceptual loads irrespective of the letter shape loads. When only the target and the flanker were colored whereas the distractors in the central array were not (Experiment 3), the task-irrelevant color information reduced or eliminated the impact of letter shape perceptual load on the congruency effects in responding to the letter shape. These findings suggested that selective attention to multidimensional objects follows the general principles suggested by the perceptual load theory, but the bottom-up perceptual saliency plays a primary role in the distribution of attentional resources over objects and dimensions.

Adolescent↗

PubMed2006

Isatin compounds as noncovalent SARS coronavirus 3C-like protease inhibitors.

A series of isatin derivatives were synthesized and tested against SARS CoV 3C-like protease. Substitutions at the N-1 and C-5 positions were examined to elucidate the differences in substrate binding sites of the rhinovirus 3C protease and SARS CoV 3C-like protease. Compound 5f shows significant inhibition with an IC(50) of 0.37 microM. Further study showed that, unlike the irreversible covalent binding of isatin derivatives to human rhinovirus 3C protease, the compounds tested in this study are all noncovalent reversible inhibitors.

Coronavirus 3C Proteases↗

PubMed2006

Only one protomer is active in the dimer of SARS 3C-like proteinase.

The severe acute respiratory syndrome coronavirus 3C-like protease has been proposed to be a key target for structurally based drug design against SARS. The enzyme exists as a mixture of dimer and monomer, and only the dimer was considered to be active. In this report, we have investigated, using molecular dynamics simulation and mutational studies, the problems as to why only the dimer is active and whether both of the two protomers in the dimer are active. The molecular dynamics simulations show that the monomers are always inactive, that the two protomers in the dimer are asymmetric, and that only one protomer is active at a time. The enzyme activity of the hybrid severe acute respiratory syndrome coronavirus 3C-like protease of the wild-type protein and the inactive mutant proves that the dimerization is important for enzyme activity and only one active protomer in the dimer is enough for the catalysis. Our simulations also show that the right conformation for catalysis in one protomer can be induced upon dimer formation. These results suggest that the enzyme may follow the association, activation, catalysis, and dissociation mechanism for activity control.

Binding Sites↗

PubMed2006

Generation and characterization of monoclonal antibodies to human keratinocyte growth factor receptor.

Keratinocyte growth factor receptor (KGFR) and fibroblast growth factor receptor (FGFR) 2c share identical amino acid sequences, except for a 46-amino acid domain in the extracellular region. Monoclonal antibodies (MAbs) specific to KGFR have not been reported nor are commercially available. In this study, we generated murine MAbs specific to KGFR in non-obese diabetic (NOD) mice using a modified Repeated Immunizations at Multiple Sites (RIMMS) technology. Stable cell lines expressing the full-length human KGFR or FGFR2c were produced to facilitate the identification of KGFR-specific MAbs. Following the initial screening of hybridoma clones with a fluorescence-based, confocal cell detection method and ELISA, KGFR-specific MAbs were selected and confirmed by flow cytometry and Western blot analyses. Antagonistic MAbs were identified using a cell-based functional assay. These KGFR MAbs will be important reagents for studying the biological function and tissue distribution of this receptor in normal and pathological conditions.

Amino Acid Sequence↗

PubMed2006

NG2 colocalizes with axons and is expressed by a mixed cell population in spinal cord lesions.

The NG2 proteoglycan is of general interest after spinal cord injury because it is expressed by oligodendrocyte progenitors (OPCs), which contribute to central nervous system remyelination; however, NG2 may inhibit axon regeneration. We and others have examined the spatiotemporal expression of NG2 after spinal cord injury (SCI). Here, we extend those observations and provide a comprehensive analysis of the distribution, phenotype, and colocalization of NG2 cells with axons in a clinically relevant model of spinal contusion. Because contusion models mimic the majority of human SCI, this information is important for understanding endogenous processes that promote and/or prevent repair. The data demonstrate that NG2 levels rise significantly between 3 and 7 days postinjury (dpi) and remain elevated chronically throughout the lesions. NG2 within the lesions could be derived from an array of infiltrating cells; thus, a panel of antibodies was used to investigate NG2 cell phenotypes. First, platelet-derived growth factor-alpha receptor (PDGFalphaR) colocalization was examined because OPCs normally express both markers. PDGFalphaR cells were present in lesions at all times examined. However, only 37% of NG2 cells coexpressed PDGFalphaR at 14 dpi, which dropped to <1% by 70 dpi. This contrasts with the nearly complete overlap in spared tissue surrounding the lesion. In contrast, 40% to 60% of NG2 cells expressed p75 and approximately 84% expressed Sox10, suggesting that many NG2 cells were nonmyelinating Schwann cells. Despite rising levels of NG2, we noted robust and sustained axon growth into the lesions, many of which were located along NG2 profiles. Thus, spinal contusion produces an NG2-rich environment into which axons grow and in which the source of NG2 appears considerably different from that in surrounding spared tissue.

Animals↗

PubMed2006

Distinct neural correlates for resolving stroop conflict at inhibited and noninhibited locations in inhibition of return.

It is well documented that the anterior cingulate cortex (ACC) and the dorsolateral prefrontal cortex (DLPFC) are intensively involved in conflict control. However, it remains unclear how these "executive" brain regions will act when the conflict control process interacts with spatial attentional orienting. In the classical spatial cueing paradigm [Posner, M. I., & Cohen, Y. (1984). Components of visual orienting. In H. Bouma & D. G. Bouwhuis (Eds.), Attention and performance X (pp. 531-556). Hillsdale, NJ: Erlbaum], response to a target is delayed when it appears at the cued location compared with at the uncued location, if the time interval between the cue and the target is greater than 300 msec. This effect of inhibition of return (IOR) can alter the resolution of Stroop conflict such that the Stroop interference effect disappears at the cued (inhibited) location [Vivas, A. B., & Fuentes, L. J. Stroop interference is affected in inhibition of return. Psychonomic Bulletin and Review, 8, 315-323, 2001]. In this event-related functional magnetic resonance study, we investigate the differential neural mechanisms underlying interactions between pre-response interference, response interference, and spatial orienting. Two types of Stroop words [incongruent response-eligible words (IE), incongruent response-ineligible words (II)] and neutral words were presented either at the cued or uncued location. The significant pre-response interference at the uncued location activated the left rostral ACC as compared with at the cued location. Moreover, although the IE words which have conflicts at both pre-response and response levels did not cause significant behavioral interference at the cued location, they activated the left DLPFC as compared with at the uncued location. Furthermore, neutral words showed significant IOR effects behaviorally, and they activated the left frontal eye field (FEF) at the uncued location relative to the cued location. These results suggest that the left rostral ACC is involved in the interaction between pre-response conflict and IOR, whereas the left DLPFC is involved in the interaction between response conflict and IOR. Moreover, the FEF is involved in shifting attentional focus to novel locations during spatial search.

Adult↗

PubMed2006

Quaternary structure, substrate selectivity and inhibitor design for SARS 3C-like proteinase.

The SARS coronavirus 3C-like proteinase is recognized as a potential drug design target for the treatment of severe acute respiratory syndrome. In the past few years, much work has been done to understand the catalytic mechanism of this target protein and to design its selective inhibitors. The protein exists as a dimer/monomer mixture in solution and the dimer was confirmed to be the active species for the enzyme reaction. Quantitative dissociation constants have been reported for the dimer by using analytic ultracentrifuge, gel filtration and enzyme assays. Though the enzyme is a cysteine protease with a chymotrypsin fold, SARS 3C-like proteinase follows the general base catalytic mechanism similar to chymotrypsin. As the enzyme can cut eleven different sites on the viral polyprotein, the substrate specificity has been studied by synthesized peptides corresponding or similar to the cleavage sites on the polyprotein. Predictive model was built for substrate structure and activity relationships and can be applied in inhibitor design. Due to the lack of potential drugs for the treatment of SARS, the discovery of inhibitors against SARS 3C-like proteinase, which can potentially be optimized as drugs appears to be highly desirable. Various groups have been working on inhibitor discovery by virtual screening, compound library screening, modification of existing compounds or natural products. High-throughput in vitro assays, auto-cleavage assays and viral replication assays have been developed for inhibition activity tests. Inhibitors with IC50 values as low as 60 nM have been reported.

Animals↗

PubMed2006

[Clinicopathologic study of post-transplant lymphoproliferative disorders].

OBJECTIVE: To study the clinical and pathologic features of post-transplant lymphoproliferative disorders (PTLD), and to investigate the clinical significance of this diagnosis. METHODS: Four cases of PTLD were studied by routine light microscopy, immunohistochemistry and in-situ hybridization and polymerase chain reaction. The clinical data and follow-up information were also reviewed. RESULTS: In the 4 cases, 3 cases occurred in renal transplant recipients and 1 in bone marrow transplant patient. In the 3 post-renal transplant patients, 2 had polymorphic PTLD and 1 had monomorphic PTLD. The post-bone marrow transplant case was classified as "early" lesion of PTLD. Epstein-Barr virus (EBV) was detected in 2 cases. All the 4 cases studied had received cyclosporine A and steroids after transplantation. The duration between organ transplantation and diagnosis of PTLD from case 1 to case 4 was 42, 7, 129, 2 months. One of the polymorphic PTLD cases belonged to clinical stage II and subsequently died of the disease. Other cases belonged to clinical stage I and were alive for 5 to 40 months after diagnosis of PTLD. CONCLUSIONS: PTLD is a lymphoproliferative disease with distinctive morphologic and clinical characteristics. An association with EBV at least in some cases is observed. The prognosis of PTLD correlates with clinical stage. It may respond to reduction in dosage of immunosuppressive agents.

Adult↗

PubMed2005

[Expression of hepatic Bcl-2 and Bax proteins in schistosome-infected mice and the role of pentoxifylline].

OBJECTIVE: To study the expression of hepatic Bcl-2 and Bax proteins in mice infected with Schistosoma japonicum and the role of pentoxifylline (PTX) in the expression. METHODS: Forty mice were randomly divided into 4 groups: one normal control group,mice in the other three groups were all infected each with 25 cercariae, the infected control group was fed for 10 weeks after infection, and 2 weeks after infection, the high dose PTX group was given PTX 360 mg/(kg x d) for 8 weeks and the low dose PTX group was given PTX 180 mg/(kg x d)also for 8 weeks. At the end of 10 weeks all the mice were killed. Bcl-2 and Bax proteins expression was detected by immunohistochemisty. RESULTS: Compared with the normal control group, the expression of Bcl-2 and Bax was significantly higher in the infected control group (P < 0.05). Bcl-2 was significantly higher in high (dose PTX group than in the infected control group and in low dose PTX group (P < 0.05). However there was no significant difference in the expression of Bax among the groups (P > 0.05). CONCLUSION: PTX treatment can significantly increase the expression of Bcl-2 in liver tissue of schistosome-infected mice in a dose-dependent manner, and may play a role against liver inflammation and schistosomiasis-related liver fibrosis.

Animals↗

PubMed2005

The N-terminal octapeptide acts as a dimerization inhibitor of SARS coronavirus 3C-like proteinase.

The 3C-like proteinase of severe acute respiratory syndrome (SARS) coronavirus has been proposed to be a key target for structural-based drug design against SARS. Accurate determination of the dimer dissociation constant and the role of the N-finger (residues 1-7) will provide more insights into the enzyme catalytic mechanism of SARS 3CL proteinase. The dimer dissociation constant of the wild-type protein was determined to be 14.0microM by analytical ultracentrifugation method. The N-finger fragment of the enzyme plays an important role in enzyme dimerization as shown in the crystal structure. Key residues in the N-finger have been studied by site-directed mutagenesis, enzyme assay, and analytical ultracentrifugation. A single mutation of M6A was found to be critical to maintain the dimer structure of the enzyme. The N-terminal octapeptide N8 and its mutants were also synthesized and tested for their potency as dimerization inhibitors. Peptide cleavage assay confirms that peptide N8 is a dimerization inhibitor with a K(i) of 2.20mM. The comparison of the inhibitory activities of N8 and its mutants indicates that the hydrophobic interaction of Met-6 and the electrostatic interaction of Arg-4 contribute most for inhibitor binding. This study describes the first example of inhibitors targeting the dimeric interface of SARS 3CL proteinase, providing a novel strategy for drug design against SARS and other coronaviruses.

Binding Sites↗

PubMed2005

The interaction between severe acute respiratory syndrome coronavirus 3C-like proteinase and a dimeric inhibitor by capillary electrophoresis.

3C-like proteinase of severe acute respiratory syndrome (SARS) coronavirus has been demonstrated to be a key target for drug design against SARS. The interaction between SARS coronavirus 3C-like (3CL) proteinase and an octapeptide interface inhibitor was studied by affinity capillary electrophoresis (ACE). The binding constants were estimated by the change of migration time of the analytes in the buffer solution containing different concentrations of SARS 3CL proteinase. The results showed that SARS 3CL proteinase was able to complex with the octapeptide competitively, with binding constants of 2.44 x 10(4) M(-1) at 20 degrees C and 2.11 x 10(4)M(-1) at 37 degrees C. In addition, the thermodynamic parameters deduced reveal that hydrophobic interaction might play major roles, along with electrostatic force, in the binding process. The ACE method used here could be developed to be an effective and simple way of applying large-scale drug screening and evaluation.

3C Viral Proteases↗

PubMed2005

The substrate specificity of SARS coronavirus 3C-like proteinase.

The 3C-like proteinase of severe acute respiratory syndrome coronavirus (SARS) has been proposed to be a key target for structural based drug design against SARS. We have designed and synthesized 34 peptide substrates and determined their hydrolysis activities. The conserved core sequence of the native cleavage site is optimized for high hydrolysis activity. Residues at position P4, P3, and P3' are critical for substrate recognition and binding, and increment of beta-sheet conformation tendency is also helpful. A comparative molecular field analysis (CoMFA) model was constructed. Based on the mutation data and CoMFA model, a multiply mutated octapeptide S24 was designed for higher activity. The experimentally determined hydrolysis activity of S24 is the highest in all designed substrates and is close to that predicted by CoMFA. These results offer helpful information for the research on the mechanism of substrate recognition of coronavirus 3C-like proteinase.

Amino Acid Sequence↗