Biomedical subjects

J Zhou

Publications and source records attributed to J Zhou.

At least 19 recordsLinked to original sources

PubMed2026

[Tafluprost/timolol fixed-dose combination versus tafluprost monotherapy for open-angle glaucoma and ocular hypertension: a multicenter, randomized, double-blind, parallel-group trial].

Objective: To evaluate the efficacy and safety of a preservative-free tafluprost/timolol maleate fixed-dose combination compared with preservative-free tafluprost monotherapy in Chinese patients with open-angle glaucoma (OAG) or ocular hypertension (OHT). Methods: This was a multicenter, randomized, double-blind, parallel-controlled clinical trial conducted across 25 centers, including the Eye & ENT Hospital of Fudan University, from January 2019 to November 2022. Patients diagnosed with OAG or OHT who required enhanced intraocular pressure (IOP) reduction after a 4-week washout period were enrolled. Participants were randomized 1∶1 to receive either tafluprost/timolol or tafluprost once daily for 3 months. The primary endpoint was the change from baseline in mean diurnal IOP (the average of measurements at 8:00, 10:00, and 16:00) at Month 3. Secondary endpoints included IOP changes at individual time points and the proportion of responders achieving predefined IOP reduction thresholds. Safety was assessed via the incidence of adverse events (AEs). Analysis of covariance (ANCOVA) using the Markov Chain Monte Carlo (MCMC) method was employed for the primary endpoint; superiority was established if the upper limit of the 95% confidence interval (CI) was<0 mmHg (1 mmHg=0.133 kPa). Continuous variables in secondary endpoints were compared using ANCOVA, and responder rates were analyzed using Fisher's exact test. Results: A total of 219 patients were enrolled (tafluprost/timolol group: n=110; tafluprost group: n=109). The primary efficacy analysis set included 215 patients (tafluprost/timolol: n=107; tafluprost: n=108). Baseline characteristics were well-balanced between the two groups. The majority of patients were male [127 (59.1%)] with a mean age of (44.80±15.71) years at screening. At Month 3, the mean diurnal IOP reduction from baseline was (6.56±3.44) mmHg in the tafluprost/timolol group and (5.36±2.94) mmHg in the tafluprost group. After adjusting for baseline IOP, the between-group difference was -1.312 mmHg (95%CI: -2.010 to -0.696); as the upper limit was<0 mmHg, tafluprost/timolol demonstrated superior IOP-lowering efficacy to tafluprost. Responder rates for IOP reductions of≥15%,≥25%, and≥30% were significantly higher in the tafluprost/timolol group (P=0.016, 0.028, and 0.032, respectively). The incidence of ocular AEs was 20.0% (22/110) in the tafluprost/timolol group and 26.6% (29/109) in the tafluprost group. The most common AE was conjunctival hyperemia, occurring in 2.7% (3/110) and 8.3% (9/109) of the groups, respectively. Conclusion: Compared with preservative-free tafluprost monotherapy, the tafluprost/timolol combination provides significantly greater IOP reduction in patients with OAG and OHT, while maintaining a favorable safety profile.

Humans↗

PubMed2007

Arsenic trioxide and acute promyelocytic leukemia: clinical and biological.

Arsenic has recently been identified as an effective drug in the treatment of newly diagnosed and relapsed acute promyelocytic leukemia. Indeed, arsenic trioxide combined with all-trans retinoic acid shows a synergistic effect. Mechanistically, arsenic targets the key leukemogenic protein PML-RARalpha, setting up a new example of molecular target-based cancer therapy.

Antineoplastic Agents↗

PubMed2007

Contact damage in an yttria stabilized zirconia: implications.

This paper presents the results of a combined experimental and computational study of contact damage in a 3 mole% yttria partially stabilized zirconia (3-YSZ) that is relevant to hip implants and dental restorations. Contact-induced loading in real applications is idealized using Hertzian contact model to explain plasticity phenomena and failure mechanisms observed under monotonic and cyclic loading. Under monotonic loading, the elastic moduli increase with increasing loading levels. Under cyclic loading, the ceramic specimens fail with progressive cone cracking. X-ray analyses reveal that stress-induced phase transformation (from tetragonal to monoclinic phases) occurs under cyclic contact loading above the critical load levels (approximately 8.5 kN). Furthermore, when the cyclic loading level (5.0 kN) is less than a critical load levels (7.5 kN) that is required to induce surface cone cracks, significant plastic damage is observed in the subsurface zone underneath the contact area. These suggest that the cyclic contact loading induce both plastic damage and tetragonalto-monoclinic phase transformation in the 3-YSZ, leading to significant degradation in long-term strength. The implications of the results are discussed for the design of zirconia femoral heads in total hip replacements and zirconia crowns in dental restoration.

Biocompatible Materials↗

PubMed2007

Protein array autoantibody profiles for insights into systemic lupus erythematosus and incomplete lupus syndromes.

The objective of this study was to investigate the prevalence and clinical significance of a spectrum of autoantibodies in systemic lupus erythematosus and incomplete lupus syndromes using a proteome microarray bearing 70 autoantigens. Microarrays containing candidate autoantigens or control proteins were printed on 16-section slides. These arrays were used to profile 93 serum samples from patients with systemic lupus erythematosus (SLE (n = 33), incomplete LE (ILE; n = 23), first-degree relatives (FDRs) of SLE patients (n = 20) and non-autoimmune controls (NC; n = 17). Data were analysed using the significance analysis of microarray (SAM) and clustering algorithms. Correlations with disease features were determined. Serum from ILE and SLE patients contained high levels of IgG autoantibodies to 50 autoantigens and IgM autoantibodies to 12 autoantigens. Elevated levels of at least one IgG autoantibody were detected in 26% of SLE and 19% of ILE samples; elevated IgM autoantibodies were present in 13% of SLE and 17% of ILE samples. IgG autoantibodies segregated into seven clusters including two specific for DNA and RNA autoantigens that were correlated with the number of lupus criteria. Three IgG autoantibody clusters specific for collagens, DNA and histones, were correlated with renal involvement. Of the four IgM autoantibody clusters, two were correlated negatively with the number of lupus criteria; none were correlated with renal disease. The IgG : IgM autoantibody ratios generally showed a stepwise increase in the groups following disease burden from NC to SLE. Insights derived from the expanded autoantibody profiling made possible with the antigen array suggest differences in autoreactivity in ILE and SLE. Determining whether the IgM aurotreactivity that predominates in ILE represents an early stage prior to IgG switching or is persistent and relatively protective will require further longitudinal studies.

Adult↗

PubMed2007

Heterogeneity in the collagen-degrading ability of Porphyromonas gingivalis-stimulated human gingival fibroblasts.

BACKGROUND AND OBJECTIVE: The purpose of this study was to characterize the heterogeneity of the collagen-degrading ability of different human gingival fibroblast cell lines treated with Porphyromonas gingivalis supernatant. MATERIAL AND METHODS: Seven human gingival fibroblast cell lines were analyzed for their ability to cleave Type I collagen in the presence and absence of culture supernatant from P. gingivalis ATCC 33277 (10% v/v). The matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) produced by these human gingival fibroblasts were monitored at the protein level by zymography and/or western blot analyses, as well as at the mRNA level by reverse transcription-polymerase chain reaction. RESULTS: The collagen-degrading ability of the human gingival fibroblasts increased in four cell lines (aggressive) and was only slightly altered in the other three cell lines (nonaggressive) in the presence of P. gingivalis supernatant. MMP-1, MMP-2, and MMP-3 more readily underwent activation while the TIMP-1 level was decreased in the conditioned media from a P. gingivalis-treated human gingival fibroblast aggressive cell line. None of these was altered in a nonaggressive cell line. The mRNA levels of the MMPs and TIMPs were only slightly different between these two cell lines. CONCLUSION: Heterogeneity exists in human gingival fibroblasts in regard to their collagenolytic activity in the presence of P. gingivalis.

Cell Line↗

PubMed2006

Evaluation of expression of midkine in oral squamous cell carcinoma and its correlation with tumour angiogenesis.

Midkine, a new member of the heparin-binding growth factor family, was found recently to have a high expression level in many carcinoma specimens, including oesophagus, gall, bladder, pancreas, colorectum, breast and lung carcinomas, but few relevant studies have been performed. The aim of this study was to investigate the expression of midkine in oral squamous cell carcinoma (OSCC) and its correlation with tumour angiogenesis. Surgical specimens from 62 cases of OSCC and 10 cases of normal oral mucosa were examined by immunohistochemistry. The relationship between expression of midkine and the clinicopathological data and tumour angiogenesis was analysed. Midkine proteins were overexpressed in OSCC. The level of midkine expression was found to be significantly correlated with tumour size (P = 0.01), clinical stage (P = 0.002) and prognosis (P = 0.038). High midkine expression was associated with higher tumour angiogenesis as reflected by increased vascular endothelial growth factor expression (P = 0.005) and higher microvessel density (P = 0.004). These results indicate that midkine may be of great value in assessing the development and prognosis of OSCC, and could be taken as a new target for OSCC therapy.

Adult↗

PubMed2006

Synthesis and electrical transport of single-crystal NH4V3O8 nanobelts.

Monoclinic NH(4)V(3)O(8) single-crystalline nanobelts with widths of 80-180 nm, thicknesses of 50-100 nm, and lengths up to tens of micrometers have been synthesized at large scale in an ammonium metavanadate solution by a templates/catalysts-free route. Such nanobelts grow along the direction of [010]. The individual NH(4)V(3)O(8) nanobelt exhibits nonlinear, symmetric current/voltage (I/V) characteristics, with a conductivity of 0.1-1 S/cm at room temperature and a dielectric constant of approximately 130. The dominant conduction mechanism is based on small polaron hopping due to ohmic mechanism at low electric field below 249 V/cm due to Schottky emission at medium electric field between 249 and 600 V/cm and due to the Poole-Frenkel emission mechanism at high field above 600 V/cm.

Catalysis↗

PubMed2006

Babesia parasites develop and are transmitted by the non-vector soft tick Ornithodoros moubata (Acari: Argasidae).

Ornithodoros moubata ticks were fed on blood infected with Babesia equi. However, the parasites were quickly cleared as evidenced by the disappearance of B. equi-specific ribosomal RNA from the ticks. We hypothesized that if the Babesia parasite can escape midgut-associated barriers a non-vector tick can become infected with Babesia. To test this hypothesis, B. equi parasite-infected blood from in vitro culture was injected into the haemocoel of ticks. B. equi-specific rRNA was surprisingly detected 45 days after injection even in the eggs. Babesia-free dogs were infested with O. moubata ticks that were infected by inoculation with B. gibsoni-infected red blood cells. Parasitaemia and antibody production against Bg-TRAP of B. gibsoni increased gradually. These results indicate that O. moubata may be a useful vector model for Babesia parasites and also a very important tool for studies on tick immunity against Babesia parasites and tick-Babesia interactions.

Animals↗

PubMed2006

The elusive role of store depletion in the control of intracellular calcium release.

The contractile cycle of striated muscles, skeletal and cardiac, is controlled by a cytosolic [Ca2+] transient that requires rapid movements of the ion through channels in the sarcoplasmic reticulum (SR). A functional signature of these channels is their closure after a stereotyped time lapse of Ca2+ release. In cardiac muscle there is abundant evidence that termination of release is mediated by depletion of the Ca2+ store, even if the linkage mechanism remains unknown. By contrast, in skeletal muscle the mechanisms of release termination are not understood. This article reviews measurements of store depletion, the experimental evidence for dependence of Ca2+ release on the [Ca2+] level inside the SR, as well as tests of the molecular nature of putative intra-store Ca2+ sensors. Because Ca2+ sparks exhibit the basic release termination mechanism, much attention is dedicated to the studies of store depletion caused by sparks and its relationship with termination of sparks. The review notes the striking differences in volume, content and buffering power of the stores in cardiac vs. skeletal muscle, differences that explain why functional depletion is much greater for cardiac than skeletal muscle stores. Because in skeletal muscle store depletion is minimal and reduction in store [Ca2+] does not appear to greatly inhibit Ca2+ release, it is concluded that decrease in free SR [Ca2+] does not mediate physiological termination of Ca2+ release in this type of muscle. In spite of the apparent absence of store depletion and its putative channel closing effect, termination of Ca2+ sparks is faster and more robust in skeletal than cardiac muscle. A gating role of a hypothetical "proximate store" constituted by polymers of calsequestrin and associated proteins is invoked in an attempt to preserve a role for store depletion and unify mechanisms in both types of striated muscle.

Animals↗

PubMed2006

Microarray applications in microbial ecology research.

Microarray technology has the unparalleled potential to simultaneously determine the dynamics and/or activities of most, if not all, of the microbial populations in complex environments such as soils and sediments. Researchers have developed several types of arrays that characterize the microbial populations in these samples based on their phylogenetic relatedness or functional genomic content. Several recent studies have used these microarrays to investigate ecological issues; however, most have only analyzed a limited number of samples with relatively few experiments utilizing the full high-throughput potential of microarray analysis. This is due in part to the unique analytical challenges that these samples present with regard to sensitivity, specificity, quantitation, and data analysis. This review discusses specific applications of microarrays to microbial ecology research along with some of the latest studies addressing the difficulties encountered during analysis of complex microbial communities within environmental samples. With continued development, microarray technology may ultimately achieve its potential for comprehensive, high-throughput characterization of microbial populations in near real time.

Bacteria↗

PubMed2006

Stability in a denitrifying fluidized bed reactor.

This study evaluates changes in the microbial community structure and function of a pilot-scale denitrifying fluidized bed reactor during periods of constant operating conditions and periods of perturbation. The perturbations consisted of a shutdown period without feed, two disturbances in which biofilms were mechanically sheared from carrier particles, and a twofold step increase in feed nitrate concentration. In the absence of perturbations, nitrate removal was stable and consistently greater than 99%. The structure and dynamics of the microbial community were studied using cloning and sequencing techniques and terminal restriction fragment length polymorphism (T-RFLP) of the SSU rRNA gene. Under unperturbed operating conditions, stable function was accompanied by high constancy and low variability of community structure with the majority of terminal restriction fragments (T-RFs) appearing throughout operation at consistent relative abundances. Several of the consistently present T-RFs correlated with clone sequences closely related to Acidovorax (98% similarity), Dechloromonas (99% similarity), and Zoogloea (98% similarity), genera recently identified by molecular analyses of similar systems. Significant changes in community structure and function were not observed after the shutdown period. In contrast, following the increase in loading rate and the mechanical disturbances, new T-RFs appeared. After both mechanical disturbances, function and community structure recovered. However, function was much more resilient than community structure. The similarity of response to the mechanical disturbances despite differences in community structure and operating conditions suggests that flexible community structure and potentially the activity of minor members under nonperturbation conditions promotes system recovery.

Biodegradation, Environmental↗

PubMed2006

Altered vitamin D metabolism in type II diabetic mouse glomeruli may provide protection from diabetic nephropathy.

The db/db mouse develops features of type II diabetes mellitus as the result of impaired signaling through its abnormal leptin receptor. In spite of accurate metabolic features of diabetes, renal disease manifestations in these mice are not as severe as in humans suggesting the presence of protective genes. There is a growing body of evidence in humans for the relevance of vitamin D in diabetes. Here we followed a large cohort of db/db mice and their non-diabetic db/+ littermates. Transcriptional profiling revealed significant upregulation of 23 genes involved in Ca2+ homeostasis and vitamin D metabolism in db/db glomeruli relative to db/+ glomeruli. Increased glomerular expression of vitamin D3 1alpha-hydroxylase, vitamin D binding protein, calbindins D9K and D28K, and calcyclin mRNA was confirmed by quantitative reverse transcription-polymerase chain reaction in 20-, 36-, and 52-week-old db/db glomeruli. Although vitamin D3 1alpha-hydroxylase protein was primarily expressed and upregulated in db/db renal tubules, it was also expressed in glomerular podocytes in vivo. Serum 1,25-dihydroxyvitamin D3 and urinary Ca2+ excretion were increased >3-fold in db/db mice compared to db/+ mice. Cultured glomerular podocytes had mRNA for vitamin D3 1alpha-hydroxylase, vitamin D receptor, and calbindin D28K, each of which was increased in high glucose conditions. High glucose also led to enhanced production of fibronectin and collagen IV protein, which was blocked by 1,25-dihydroxyvitamin D3. These results show that vitamin D metabolism is altered in db/db mice leading to metabolic and transcriptional effects. The podocyte is affected by paracrine and potentially autocrine effects of vitamin D, which may explain why db/db mice are resistant to progressive diabetic nephropathy.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗

PubMed2006

Measurement of forces inside a three-dimensional pile of frictionless droplets.

We present systematic and detailed measurements of interparticle contact forces inside three-dimensional piles of frictionless liquid droplets. We measured long-range chainlike correlations of the directions and magnitudes of large forces, thereby establishing the presence of force chains in three dimensions. Our correlation definition provides a chain persistence length of 10 mean droplet diameters, decreasing as load is applied to the pile. We also measured the angles between contacts and showed that the chainlike arrangement arises from the balance of forces. Moreover, we found that piles whose height was comparable to the chain persistence length exhibited substantially greater strain hardening than did tall piles, which we attributed to the force chains. Together, the results establish a connection between the microscopic force network and the elastic response of meso- or macroscopic granular piles. The conclusions drawn here should be relevant in jammed systems generally, including concentrated emulsions and piles of sand or other heavy particles.

Journal Article↗

PubMed2006

Oncolytic adenovirus-mediated transfer of the antisense chk2 selectively inhibits tumor growth in vitro and in vivo.

Screening and identifying molecules target to checkpoint pathways has fostered the development of checkpoint-based anticancer strategies. Among these targets, inhibition of chk2 may induce cell death for tumors whose growth depends on enhanced chk2 activity. However, improvement of the potency and specificity of such therapeutics remains a major challenge. To resolve this problem, we constructed M3, a novel recombinant adenovirus with a 27-bp deletion in E1A CR2 region by which to realize tumor-specific replication, and an 829-bp of antisense chk2 fragment inserted into the E3 coding region. In this design, M3 exploited the native adenovirus E3 promoters to express antisense chk2 cDNA in a viral replication-dependent fashion, and preferentially silenced the chk2 gene in tumor cells. In vitro and in vivo assays confirmed that downregulated chk2 expression induced by M3 infection was tumor-specific and virus replication-dependent. Furthermore, systemic administration of M3 combined with a low dose of cisplatin cured 75% (9/12) of orthotopic hepatic carcinoma mouse models that were otherwise resistant to cisplatin. Our results indicated that the upcoming development in this field would improve the antitumor efficacy and maximize the synergistic effect of oncolytic viruses administered with traditional chemotherapy or radiotherapy.

Adenoviridae↗

PubMed2006

MPZL1/PZR, a novel candidate predisposing schizophrenia in Han Chinese.

The MPZL1/PZR gene has been mapped to 1q23.3, located in close proximity to a recognized schizophrenia susceptibility locus. Recently, the MPZL1/PZR gene has been found to be significantly upregulated in schizophrenia brain tissue and to play an important role in cell signaling, thus indicating that MPZL1/PZR could be a potential schizophrenia marker. To test this hypothesis, we selected three single nucleotide polymorphisms (SNPs) for genotyping in 523 Han Chinese trios. We found that two individual SNPs were significant at the Bonferroni's corrected significance level P<0.017: rs3767444 (chi2=6.299, P=0.0121) and rs2051656 (chi2=9.856, P=0.0017). Haplotype transmission/disequilibrium tests revealed a significant association with the disease (global P-value=1.064 x 10(-6)), but no specific transmission distortions. Thus, we propose that the MPZL1/PZR gene may be important in the predisposition to schizophrenia among Han Chinese.

Adult↗

PubMed2006

Phylogenetic and functional biomakers as indicators of bacterial community responses to mixed-waste contamination.

Few studies have demonstrated changes in community structure along a contaminant plume in terms of phylogenetic, functional, and geochemical changes, and such studies are essential to understand how a microbial ecosystem responds to perturbations. Clonal libraries of multiple genes (SSU rDNA, nirK, nirS, amoA, pmoA, and dsrAB) were analyzed from groundwater samples (n = 6) that varied in contaminant levels, and 107 geochemical parameters were measured. Principal components analyses (PCA) were used to compare the relationships among the sites with respect to the biomarker (n = 785 for all sequences) distributions and the geochemical variables. A major portion of the geochemical variance measured among the samples could be accounted for by tetrachloroethene, 99Tc, No3, SO4, Al, and Th. The PCA based on the distribution of unique biomarkers resulted in different groupings compared to the geochemical analysis, but when the SSU rRNA gene libraries were directly compared (deltaC(xy) values) the sites were clustered in a similar fashion compared to geochemical measures. The PCA based upon functional gene distributions each predicted different relationships among the sites, and comparisons of Euclidean distances based upon diversity indices for all functional genes (n = 432) grouped the sites by extreme or intermediate contaminant levels. The data suggested that the sites with low and high perturbations were functionally more similar than sites with intermediate conditions, and perhaps captured the overall community structure better than a single phylogenetic biomarker. Moreover, even though the background site was phylogenetically and geochemically distinct from the acidic sites, the extreme conditions of the acidic samples might be more analogous to the limiting nutrient conditions of the background site. An understanding of microbial community-level responses within an ecological framework would provide better insight for restoration strategies at contaminated field sites.

Bacteria↗

PubMed2006

Highly purified CD44+ prostate cancer cells from xenograft human tumors are enriched in tumorigenic and metastatic progenitor cells.

CD44 is a multifunctional protein involved in cell adhesion and signaling. The role of CD44 in prostate cancer (PCa) development and progression is controversial with studies showing both tumor-promoting and tumor-inhibiting effects. Most of these studies have used bulk-cultured PCa cells or PCa tissues to carry out correlative or overexpression experiments. The key experiment using prospectively purified cells has not been carried out. Here we use FACS to obtain homogeneous CD44(+) and CD44(-) tumor cell populations from multiple PCa cell cultures as well as four xenograft tumors to compare their in vitro and in vivo tumor-associated properties. Our results reveal that the CD44(+) PCa cells are more proliferative, clonogenic, tumorigenic, and metastatic than the isogenic CD44(-) PCa cells. Subsequent molecular studies demonstrate that the CD44(+) PCa cells possess certain intrinsic properties of progenitor cells. First, BrdU pulse-chase experiments reveal that CD44(+) cells colocalize with a population of intermediate label-retaining cells. Second, CD44(+) PCa cells express higher mRNA levels of several 'stemness' genes including Oct-3/4, Bmi, beta-catenin, and SMO. Third, CD44(+) PCa cells can generate CD44(-) cells in vitro and in vivo. Fourth, CD44(+) PCa cells, which are AR(-), can differentiate into AR(+) tumor cells. Finally, a very small percentage of CD44(+) PCa cells appear to undergo asymmetric cell division in clonal analyses. Altogether, our results suggest that the CD44(+) PCa cell population is enriched in tumorigenic and metastatic progenitor cells.

Animals↗

PubMed2006

Adenoviral gene transfer of a mutant surfactant enzyme ameliorates pseudomonas-induced lung injury.

Surfactant deficiency is an important contributor to the acute respiratory distress syndrome, a disorder that commonly occurs after bacterial sepsis. CTP:phosphocholine cytidylyltransferase (CCTalpha) is the rate-limiting enzyme required for the biosynthesis of dipalmitoylphosphatidylcholine (DPPC), the major phospholipid of surfactant. In this study, a cDNA encoding a novel, calpain-resistant mutant CCTalpha enzyme was delivered intratracheally in mice using a replication-deficient adenovirus 5 CTP:phosphocholine cytidylyltransferase construct (Ad5-CCT(Penta)) in models of bacterial sepsis. Ad5-CCT(Penta) gene transfer produced high-level CCTalpha gene expression, increased alveolar surfactant (DPPC) levels and improved lung surface tension and pressure-volume relationships relative to control mice. Pseudomonas aeruginosa (PA103) decreased DPPC synthesis, in part, via calpain-mediated degradation of CCTalpha. Deleterious effects of Pseudomonas on surfactant were lessened after infection with a mutant strain lacking the type III exotoxin, Exo U. Replication-deficient adenovirus 5 CTP:phosphocholine cytidylyltransferase gene delivery improved lung biophysical properties by optimizing surface activity in this Pseudomonas model of proteinase-mediated lung injury. The studies are the first demonstration of in vivo gene transfer of a lipogenic enzyme resulting in improved lung mechanics. The studies suggest that augmentation of DPPC synthesis via gene delivery of CCTalpha can attenuate impaired lung function in surfactant-deficient states such as bacterial sepsis.

1,2-Dipalmitoylphosphatidylcholine↗