Search PubMed⌕ Search

Biomedical subjects

Wei Lu

Publications and source records attributed to Wei Lu.

At least 19 recordsLinked to original sources
PubMed2026

Efficacy of Oral Baicalin in Canine Atopic Dermatitis: A Randomised Placebo Controlled Trial.

BACKGROUND: Baicalin has shown efficacy in various dermatitis models in animals. However, its therapeutic effects on naturally occurring canine atopic dermatitis (cAD) have not been evaluated. OBJECTIVE: To evaluate the efficacy and safety of baicalin in dogs with cAD. ANIMALS: 56 client-owned dogs were enrolled. MATERIALS AND METHODS: All dogs were randomly divided to receive oral baicalin or placebo over a 90day period. All subjects had veterinary evaluations using the Canine Atopic Dermatitis Extent and Severity Index, 4th iteration (CADESI-04) during the trial and owners were requested to evaluate itching using the pruritus Visual Analog Scale (PVAS) and to complete a quality-of-life (QoL) questionnaire at Day (D)0 and D90. Additionally, the transepidermal water loss (TEWL), total serum IgE levels (IgE), complete blood count and serum biochemical results were measured at D0 and D90. RESULTS: The significant decreases in CADESI-04 (p&#x2009;<&#x2009;0.001), PVAS (p&#x2009;<&#x2009;0.001), TEWL (p&#x2009;=&#x2009;0.014), IgE (p&#x2009;<&#x2009;0.001) and QoL scores (p&#x2009;<&#x2009;0.001) were observed in the baicalin group D90 compared to baseline. When compared to placebo, the baicalin group had significantly lower scores in CADESI-4 and PVAS (p&#x2009;<&#x2009;0.001). A significantly higher proportion of subjects in the baicalin group showed a good-to-excellent treatment response (82.1%) compared to those in the placebo group (35.7%). The treatment was well tolerated. CONCLUSIONS AND RELEVANCE: Baicalin had a significant benefit in alleviating pruritus and reducing clinical signs in dogs with mild-to-moderate cAD and was well tolerated.

Animals↗
PubMed2026

Genetically predicted associations between blood cell perturbation responses and bronchiectasis through immune mediation: A Mendelian Randomization study.

BACKGROUND: Bronchiectasis is a chronic airway disease characterized by persistent inflammation and structural damage, with substantial clinical and etiologic heterogeneity. Although previous studies have identified associations between blood cells and bronchiectasis, the causal relationships remain unclear. Moreover, the mechanisms underlying blood cell perturbation responses and their potential mediation by immune cells in disease progression are largely unexplored. METHODS: Two-sample Mendelian randomization (MR) analysis was used to explore genetically predicted associations among immune cell traits, blood cell perturbation response phenotypes, and bronchiectasis, based on genome-wide association study summary data. Mediation MR analysis was further applied to assess whether immune cells mediate these associations. Multiple sensitivity analyses, including tests for heterogeneity and horizontal pleiotropy, were performed to evaluate the validity and robustness. RESULTS: Five blood cell perturbation response phenotypes and twenty-nine immune cell traits showed significant genetically predicted associations with bronchiectasis. Mediation analysis showed that natural killer (NK) cell absolute count partially mediated the causal effect between the eosinophil perturbation response and bronchiectasis, with a mediation proportion of 9.626%. CD38 on transitional B cells mediated the causal effect between the monocyte perturbation response and bronchiectasis, with a mediation proportion of 10.580%. Additionally, CD45 on NK cells played a mediating role in the association between the white blood cell perturbation response and bronchiectasis, with a mediation proportion of 10.651%. CONCLUSION: This study systematically explores genetically predicted associations between blood cell perturbation responses and bronchiectasis and highlights potential immune-mediated pathways. These exploratory findings provide novel genetic insights into the pathogenesis of bronchiectasis and identify potential therapeutic targets for future strategies.

Humans↗
PubMed2025

Population-Specific Immunogenomic Alterations in Gallbladder Cancer and Prognostic Significance.

Gallbladder carcinoma is a deadly disease with a poor prognosis, and recent clinical data suggest only a modest benefit of PD1/PDL1 inhibitors in this disease. Optimizing immunotherapeutic approaches will require a detailed understanding of the immunogenomic landscape of this disease worldwide. We combined targeted next-generation sequencing and immunohistochemistry to create detailed immunogenomic landscapes from 2 cohorts of gallbladder cancer cases from the United States (n = 60) and Chile (n = 62). Mutations in TP53, SMAD4, KRAS, PIK3CA, ARID2, ARID1A, ATM, FBXW7, ERBB2, and NF1 were found in both the US and Chilean primary cohorts, as well as amplifications in ERBB2, CCNE1, MDM2/CDK4, and CCND1. Despite similar mutation profiles, the immune profiles were distinct, with the Latin American cohort having higher densities of biomarkers associated with CD4+ T cells and PD-1 but lower densities of CD68+ macrophages compared with the North American cohort. Clustering and correlation analyses suggest novel immune subgroups and clinical associations independently of any specific mutations. Additionally, supported by multiplexed single-cell imaging technology, we identified low CD4 and high V-domain Ig suppressor of T cell activation as a candidate biomarker pair of poor outcomes. In summary, our findings highlight the importance of sensitivity to geographic location when considering therapeutic developments and pave a path for further immune investigations of this understudied disease.

Humans↗
PubMed2007

Aclarubicin-loaded cationic albumin-conjugated pegylated nanoparticle for glioma chemotherapy in rats.

Traditional glioma chemotherapy with those second-line drugs such as anthracyclines usually failed because they are inaccessible to blood-brain barrier (BBB) in tumor. In our study, we incorporated aclarubicin (ACL) into cationic albumin-conjugated pegylated nanoparticle (CBSA-NP-ACL) to determine its therapeutic potential of rats with intracranially implanted C6 glioma cells. When labeled with fluorescent probe, 6-coumarin, CBSA-NP was shown to accumulate much more in tumor mass than nanoparticle without conjugated CBSA (NP) 1 hr post intravenous injection, as well as better retention after 24 hr. Tumor drug concentration of CBSA-NP-ACL displayed 2.6- and 3.3-fold higher than that of NP-ACL and ACL solution 1 hr post injection, while 2.7 and 6.6-fold higher after 24 hr, respectively. Moreover, using tumor microdialysis sampling, AUC(0-24 hr) of free drug amount in tumor interstitium delivered by CBSA-NP-ACL was about 2.0- and 2.7-fold higher than that of NP-ACL and ACL solutions, respectively. When the tumor rat model was subjected to 4 cycles of 2 mg/kg of ACL in different formulations, a significant increase of median survival time was found in the group of CBSA-NP-ACL compared with that of saline control animals, animals treated with NP-ACL and ACL solution. By terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling, CBSA-NP-ACL can extensively make the tumor cell apoptosis. Histochemical evaluation by periodic acid Shiff staining and biochemical analysis depicted that the incorporation of ACL into CBSA-NP reduced its toxicity to liver, kidney and heart. Besides, CBSA-NP-ACL was not shown to open tight junction evaluated by BBB coculture. It was concluded that CBSA-NP-ACL could have a therapeutic potential for treatment of glioma.

Aclarubicin↗
PubMed2007

Expression and characterization of recombinant human micro-plasminogen.

Micro-plasminogen (microPlg) gene amplified from human liver cells by reverse transcription PCR was inserted into expression vector pET-28a (pET-28a/microPlg) and transformed into E. coli strain BL21(DE3). Recombinant human micro-plasminogen (rh-microPlg) was over-expressed as inclusion bodies when induced with IPTG. After renaturation and purification, 16 mg rh-microPlg/l was obtained with a homogeneity of 95% (w/w). Pro-urokinase (proUK)-induced rh-microPlg activation was significantly faster than when Glu-plasminogen was the substrate. The catalytic efficiency of urokinase (UK) activation of rh-microPlg was twice that of Glu-plasminogen. While recombinant human micro-plasmin (rh-microPlm) and Lys-plasmin had a similar amidolytic activity against a small substrate, D-valyl-L-leucyllysine-p-nitroaniline dihydrochloride, Lys-plasmin activated proUK with a catalytic efficiency about fourfold greater than did rh-microPlm. These results suggested that the kringle 1-5 domain of plasminogen and plasmin may modify both UK activation of plasminogen and plasmin activation of proUK, respectively.

Catalysis↗
PubMed2007

Screening for novel PAX3 polymorphisms and risks of spina bifida.

BACKGROUND: PAX3 plays an important role in mammalian embryonic development. Known mutations in PAX3 are etiologically associated with Waardenburg syndrome and syndromic neural tube defects (NTDs). Mutations in the murine homologue, pax3, are responsible for the phenotype of splotch mice, in which nullizygotes are 100% penetrant for NTDs. METHODS: The study sample included 74 infants with spina bifida (cases) and 87 nonmalformed infant controls. The conserved paired-box domain as well as the upstream genomic region of PAX3 were subjected to resequencing and those identified SNPs were evaluated as haplotypes. The associations of haplotypes for selected gene regions and the risks of spina bifida were further studied. RESULTS: Nineteen SNPs were observed; 15 observed in controls had been submitted to the National Center for Biotechnology Information (NCBI) database with allele frequencies. The PAX3 gene variant T-1186C (rs16863657) and its related haplotype, TCTCCGCCC of nine SNPs, were found to be associated with an increased risk of spina bifida, with an OR of 3.5 (95% CI: 1.2-10.0) among Hispanic Whites. CONCLUSIONS: Our analyses indicated that PAX3 SNPs were not strong risk factors for human spina bifida. However, additional follow-up of the PAX3 gene variant T-1186C (rs16863657) and its related haplotype, TCTCCGCCC, may be important in other populations.

Case-Control Studies↗
PubMed2006

CHKA and PCYT1A gene polymorphisms, choline intake and spina bifida risk in a California population.

BACKGROUND: Neural tube defects (NTDs) are among the most common of all human congenital defects. Over the last two decades, accumulating evidence has made it clear that periconceptional intake of folic acid can significantly reduce the risk of NTD affected pregnancies. This beneficial effect may be related to the ability of folates to donate methyl groups for critical physiological reactions. Choline is an essential nutrient and it is also a methyl donor critical for the maintenance of cell membrane integrity and methyl metabolism. Perturbations in choline metabolism in vitro have been shown to induce NTDs in mouse embryos. METHODS: This study investigated whether single nucleotide polymorphisms (SNPs) in human choline kinase A (CHKA) gene and CTP:phosphocholine cytidylytransferase (PCYT1A) gene were risk factors for spina bifida. Fluorescence-based allelic discrimination analysis was performed for the two CHKA intronic SNPs hCV1562388 (rs7928739) and hCV1562393, and PCYT1A SNP rs939883 and rs3772109. The study population consisted of 103 infants with spina bifida and 338 non-malformed control infants who were born in selected California counties in the period 1989-1991. RESULTS: The CHKA SNP hCV1562388 genotypes with at least one C allele were associated with a reduced risk of spina bifida (odds ratio = 0.60, 95%CI = 0.38-0.94). The PCYT1A SNP rs939883 genotype AA was associated with a twofold increased risk of spina bifida (odds ratio = 1.89, 95% CI = 0.97-3.67). These gene-only effects were not substantially modified by analytic consideration to maternal periconceptional choline intake. CONCLUSION: Our analyses showed genotype effects of CHKA and PCYT1A genes on spina bifida risk, but did not show evidence of gene-nutrient interactions. The underlying mechanisms are yet to be resolved.

California↗
PubMed2006

Cationic albumin-conjugated pegylated nanoparticles allow gene delivery into brain tumors via intravenous administration.

Patients with malignant gliomas have a poor prognosis because these tumors do not respond well to conventional treatments. Studies of glioma xenografts suggest that they may be amenable to gene therapy with cytotoxic genes, such as the proapoptotic Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL). Gene therapy of gliomas ideally employs i.v. given vectors, thus excluding viral vectors as they cannot cross the brain microvascular endothelium or blood-brain barrier. Recently, we reported the synthesis of cationic albumin-conjugated pegylated nanoparticles (CBSA-NP) and showed their accumulation in mouse brain cells upon i.v. administration. In this study, plasmid pORF-hTRAIL (pDNA) was incorporated into CBSA-NP, and the resulting CBSA-NP-hTRAIL was evaluated as a nonviral vector for gene therapy of gliomas. Thirty minutes after transfection of C6 glioma cells, CBSA-NP-hTRAIL was internalized and mostly located in the cytoplasm, whereas NP-hTRAIL was entrapped in the endolysosomal compartment. At 6 and 48 hours after transfection, respectively, released pDNA was present in the nuclei and induced apoptosis. At 30 minutes after i.v. administration of CBSA-NP-hTRAIL to BALB/c mice bearing i.c. C6 gliomas, CBSA-NP-hTRAIL colocalized with glycoproteins in brain and tumor microvasculature and, via absorptive-mediated transcytosis, accumulated in tumor cells. At 24 and 48 hours after i.v. administration of CBSA-NP-hTRAIL, respectively, hTRAIL mRNA and protein were detected in normal brain and tumors. Furthermore, repeated i.v. injections of CBSA-NP-hTRAIL induced apoptosis in vivo and significantly delayed tumor growth. In summary, this study indicates that CBSA-NP-hTRAIL is a promising candidate for noninvasive gene therapy of malignant glioma.

Biological Transport↗
PubMed2006

Synthesis and evaluation of novel 8,5-fused bicyclic peptidomimetic compounds as interleukin-1beta converting enzyme (ICE) inhibitors.

An 8,5-fused bicyclic peptidomimetic ring system generated by a stereoselective ring metathesis reaction was elaborated into potent inhibitors of interleukin-1beta converting enzyme (ICE, caspase-1). Multiple compounds were found that exhibited ICE IC50 values < 10 nM and were selective over caspase-3 and caspase-8. These active analogs generally possessed good activity (IC50 values < 100 nM) in a whole cell assay measuring IL-1beta production. Pharmacokinetic analysis of the ethyl acetal prodrug form of a selected active lead revealed a compound with a reasonable plasma half-life (1.1 h) and good oral bioavailability (30%).

Animals↗
PubMed2006

Analysis of optical systems with extended depth of field using the Wigner distribution function.

We describe the use of a Wigner distribution function approach for exploring the problem of extending the depth of field in a hybrid imaging system. The Wigner distribution function, in connection with the phase-space curve that formulates a joint phase-space description of an optical field, is employed as a tool to display and characterize the evolving behavior of the amplitude point spread function as a wave propagating along the optical axis. It provides a comprehensive exhibition of the characteristics for the hybrid imaging system in extending the depth of field from both wave optics and geometrical optics. We use it to analyze several well-known optical designs in extending the depth of field from a new viewpoint. The relationships between this approach and the earlier ambiguity function approach are also briefly investigated.

Journal Article↗
PubMed2006

Effects of hydrogen bonding on current-voltage characteristics of molecular junctions.

We present a first-principles study of hydrogen bonding effect on current-voltage characteristics of molecular junctions. Three model charge-transfer molecules, 2'-amino-4,4'-di(ethynylphenyl)-1-benzenethiolate (DEPBT-D), 4,4'-di(ethynylphenyl)-2'-nitro-1-benzenethiolate (DEPBT-A), and 2'-amino-4,4'-di(ethynylphenyl)-5'-nitro-1-benzenethiolate (DEPBT-DA), have been examined and compared with the corresponding hydrogen bonded complexes formed with different water molecules. Large differences in current-voltage characteristics are observed for DEPBT-D and DEPBT-A molecules with or without hydrogen bonded waters, while relatively small differences are found for DEPBT-DA. It is predicted that the presence of water clusters can drastically reduce the conductivities of the charge-transfer molecules. The underlying microscopic mechanism has been discussed.

Journal Article↗
PubMed2006

Comparison of helical, maximum intensity projection (MIP), and averaged intensity (AI) 4D CT imaging for stereotactic body radiation therapy (SBRT) planning in lung cancer.

BACKGROUND AND PURPOSE: To compare helical, MIP and AI 4D CT imaging, for the purpose of determining the best CT-based volume definition method for encompassing the mobile gross tumor volume (mGTV) within the planning target volume (PTV) for stereotactic body radiation therapy (SBRT) in stage I lung cancer. MATERIALS AND METHODS: Twenty patients with medically inoperable peripheral stage I lung cancer were planned for SBRT. Free-breathing helical and 4D image datasets were obtained for each patient. Two composite images, the MIP and AI, were automatically generated from the 4D image datasets. The mGTV contours were delineated for the MIP, AI and helical image datasets for each patient. The volume for each was calculated and compared using analysis of variance and the Wilcoxon rank test. A spatial analysis for comparing center of mass (COM) (i.e. isocenter) coordinates for each imaging method was also performed using multivariate analysis of variance. RESULTS: The MIP-defined mGTVs were significantly larger than both the helical- (p=0.001) and AI-defined mGTVs (p=0.012). A comparison of COM coordinates demonstrated no significant spatial difference in the x-, y-, and z-coordinates for each tumor as determined by helical, MIP, or AI imaging methods. CONCLUSIONS: In order to incorporate the extent of tumor motion from breathing during SBRT, MIP is superior to either helical or AI images for defining the mGTV. The spatial isocenter coordinates for each tumor were not altered significantly by the imaging methods.

Humans↗
PubMed2006

Cell membranes and liposomes dissociate C-reactive protein (CRP) to form a new, biologically active structural intermediate: mCRP(m).

Emerging evidence indicates that C-reactive protein (CRP) has at least two conformationally distinct isoforms, i.e., pentameric CRP (pCRP) and monomeric CRP (mCRP or CRP subunit). Both CRP isoforms are proposed to play roles in inflammation and may participate in the pathogenesis of cardiovascular disease. However, the origin of mCRP in situ and the interplay between the two CRP isoforms under physiological/pathological circumstances remain elusive. Herein, by probing conformational alteration, neoepitope expression, and direct visualization using electron-microscopy, we have shown that calcium-dependent binding of pCRP to membranes, including liposomes and cell membranes, led to a rapid but partial structural change, producing molecules that express CRP subunit antigenicity but with retained native pentameric conformation. This hybrid molecule is herein termed mCRP(m). The formation of mCRP(m) was associated with significantly enhanced complement fixation. mCRP(m) can further detach from membrane to form the well-recognized mCRP isoform converted in solution (mCRP(s)) and exert potent stimulatory effects on endothelial cells. The membrane-induced pCRP dissociation not only provides a physiologically relevant scenario for mCRP formation but may represent an important mechanism for regulating CRP function.

Animals↗
PubMed2006

Tyrosine 311 is phosphorylated by c-Abl and promotes the apoptotic effect of PKCdelta in glioma cells.

In this study we characterized the phosphorylation of tyrosine 311 and its role in the apoptotic function of PKCdelta in glioma cells. We found that c-Abl phosphorylated PKCdelta on tyrosine 311 in response to H2O2 and that this phosphorylation contributed to the apoptotic effect of H2O2. In contrast, Src, Lyn, and Yes were not involved in the phosphorylation of tyrosine 311 by H2O2. A phosphomimetic PKCdelta mutant, in which tyrosine 311 was mutated to glutamic acid (PKCdeltaY311E), induced a large degree of cell apoptosis. Overexpression of the PKCdeltaY311E mutant induced the phosphorylation of p38 and inhibition of p38 abolished the apoptotic effect of the PKCdelta mutant. These results suggest an important role of tyrosine 311 in the apoptotic function of PKCdelta and implicate c-Abl as the kinase that phosphorylates this tyrosine.

Apoptosis↗
PubMed2006

Synthesis and evaluation of unsaturated caprolactams as interleukin-1beta converting enzyme (ICE) inhibitors.

Peptidomimetic compounds possessing a caprolactam ring constraint were prepared and evaluated as interleukin-1beta converting enzyme (ICE) inhibitors. The caprolactam ring was used to constrain the P3 region of our inhibitors. This strategy proved to be effective for the synthesis of ICE inhibitors, maintaining key hydrogen bond interactions with the enzyme and invoking a preferred conformation for binding. Several compounds exhibited IC(50) values less than 10nM in a caspase-1 enzyme assay and less than 100nM in a THP-1 whole cell assay measuring IL-1beta production. Two compounds, 13c and 13j, were found to have good oral bioavailability (>50%) in rats when administered as prodrugs.

Animals↗
PubMed2006

Activation of NR2B-containing NMDA receptors is not required for NMDA receptor-dependent long-term depression.

The triggering of both NMDA receptor-dependent long-term potentiation (LTP) and long-term depression (LTD) in the CA1 region of the hippocampus requires a rise in postsynaptic calcium. A prominent hypothesis has been that the detailed properties of this postsynaptic calcium signal dictate whether LTP or LTD is generated by a given pattern of synaptic activity. Recently, however, evidence has been presented that the subunit composition of the NMDA receptor (NMDAR) determines whether a synapse undergoes LTP or LTD with NR2A-containing NMDARs triggering LTP and NR2B-containing NMDARs triggering LTD. In the present study, the role of NR2B-containing synaptic NMDARs in the induction of LTD in CA1 pyramidal cells has been studied using the selective NR2B antagonists, ifenprodil and Ro25-6981. While both antagonists reduced NMDAR-mediated synaptic currents, neither prevented induction of LTD. These results demonstrate that activation of NR2B-containing NMDARs is not an absolute requirement for the induction of LTD in the hippocampus.

Animals↗
PubMed2006

Severe acute respiratory syndrome-associated coronavirus 3a protein forms an ion channel and modulates virus release.

Fourteen ORFs have been identified in the severe acute respiratory syndrome-associated coronavirus (SARS-CoV) genome. ORF 3a of SARS-CoV codes for a recently identified transmembrane protein, but its function remains unknown. In this study we confirmed the 3a protein expression and investigated its localization at the surface of SARS-CoV-infected or 3a-cDNA-transfected cells. Our experiments showed that recombinant 3a protein can form a homotetramer complex through interprotein disulfide bridges in 3a-cDNA-transfected cells, providing a clue to ion channel function. The putative ion channel activity of this protein was assessed in 3a-complement RNA-injected Xenopus oocytes by two-electrode voltage clamp. The results suggest that 3a protein forms a potassium sensitive channel, which can be efficiently inhibited by barium. After FRhK-4 cells were transfected with an siRNA, which is known to suppress 3a expression, followed by infection with SARS-CoV, the released virus was significantly decreased, whereas the replication of the virus in the infected cells was not changed. Our observation suggests that SARS-CoV ORF 3a functions as an ion channel that may promote virus release. This finding will help to explain the highly pathogenic nature of SARS-CoV and to develop new strategies for treatment of SARS infection.

Animals↗