Biomedical subjects

J Yang

Publications and source records attributed to J Yang.

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

Optimizing typhoid fever case definitions by combining serological tests in a large population study in Hechi City, China.

Blood culture-based diagnosis can only detect a fraction of the total burden of Salmonella enterica subsp. enterica serovar Typhi. The objective of the study was to detect additional typhoid fever cases through serological tests. A total of 1732 prolonged fever episodes were evaluated using three serological tests, Widal, Tubex and Typhidot-M in a typhoid fever endemic area of southern China. A case definition which included a positive Widal test (TO>or=80 & TH>A), a positive Tubex test (>or=4) and a positive Typhidot-M test, increased the detection of cases by more than twofold from 13 to 28 cases. The case definition has a specificity of 100% and a sensitivity of 39%. Case definitions based on combinations of serological tests can detect additional typhoid fever cases with higher specificity than a single serological test. Improved case detection is essential to understand the true disease burden and can help to boost the power of intervention trials.

Adolescent↗

PubMed2007

The mouse soluble GFRalpha4 receptor activates RET independently of its ligand persephin.

Glial cell line-derived neurotrophic factor (GDNF) family ligands (GFLs) all signal through the transmembrane receptor tyrosine kinase RET. The signalling complex consists of GFLs, GPI-anchored ligand binding GDNF family receptor alphas (GFRalphas) and RET. Signalling via RET is required for the development of the nervous system and the kidney, as well as for spermatogenesis. However, constitutive activation of RET is implicated as a cause in several diseases. Mutations of the RET proto-oncogene cause the inherited cancer syndrome multiple endocrine neoplasia type 2 (MEN 2). Recently, it has been suggested that mutations in the persephin binding GFRalpha4 receptor may have a potentially modifying role in MEN 2. Several naturally occurring, different splice variants of the mammalian GFRalpha4 have been reported. A 7 bp insertion-mutation in the human GFRalpha4 gene causes a shift of reading frame and thereby changes the balance between the transcripts encoding GPI-anchored and soluble GFRalpha4 receptors. We report here that the mammalian soluble GFRalpha4 can activate RET independently of its preferential ligand, persephin. Our data show that soluble GFRalpha4 can associate with, and induce, phosphorylation of RET. In addition, our data show that this isoform of GFRalpha4 can induce downstream signalling, as well as neuronal survival and differentiation, in the absence of persephin. These results suggest that, in line with the previous report, GFRalpha4 may be a candidate gene for, or modifier of, the MEN 2 diseases.

Amino Acid Sequence↗

PubMed2007

Selective inhibition of MEK1/2 reveals a differential requirement for ERK1/2 signalling in the regulation of HIF-1 in response to hypoxia and IGF-1.

The transcription factor hypoxia-inducible factor 1 (HIF-1) plays a pivotal role in tumour growth and progression, and HIF-1 is regulated through a number of signalling pathways. Here, we investigated the involvement of the mitogen-activated protein kinase (MAPK) signalling pathway in HIF-1 regulation. We found that overexpression of wild-type (WT) extracellular signal regulated protein kinase 1 (ERK1) greatly potentiated HIF-1 activation in hypoxia and HIF-1alpha induced in response to insulin growth-like factor 1 (IGF-1). Conversely, treatment of tumour cells with the MEK1/2 inhibitors PD98059 or U0216, or expression of a dominant-negative form of ERK1 blocked HIF-1 activation in hypoxia without affecting HIF-1alpha induction, localization or binding of HIF-1beta. Interestingly however, the highly selective MEK1/2 inhibitor PD184352 did not inhibit HIF-1 activity or vascular endothelial growth factor (VEGF) induced in response to hypoxia but blocked HIF-1alpha protein and HIF-1 activity induced by IGF-1 stimulation without affecting HIF-1alpha mRNA levels. Finally, we found that ERK5 phosphorylation status was not significantly affected by hypoxia in the presence or absence of PD184352. Taken together, our data suggest that although ERK1/2 signalling is important for HIF-1alpha induction and HIF-1 activity in response to IGF-1, it is dispensable for the induction of HIF-1alpha and activation of HIF-1 in response to hypoxia.

Benzamides↗

PubMed2006

Selective hair analysis of nicotine by molecular imprinted solid-phase extraction: an application for evaluating tobacco smoke exposure.

A method using a molecularly imprinted polymer (MIP) as the selective sorbent for solid-phase extraction (SPE) has been developed. Its application to the assay of hairy nicotine level among smokers and non-smokers with high-performance liquid chromatography (HPLC) and evaluation of exposures to the environmental tobacco smoke (ETS) were validated. The MIP was synthesized using nicotine as the template molecule and methacrylic acid (MAA) as the functional monomer. This MIP-SPE method provided inherent selectivity and a sensitive response to nicotine with a detection limit of 0.2 ng/ml hair at a signal-to-noise ratio of 3:1 and the limit of quantification was 0.5 ng/ml. The linearity was assessed in the range of 0.5-80 ng/ml hair, with a coefficient (r(2)) greater than 0.987. The amounts of nicotine determined in smokers and non-smokers hair were in the range of 5.1-69.5 ng/mg hair and 0.50-9.3 ng/mg hair, respectively. The reported measures of ETS exposure were significantly associated with hairy nicotine levels. This assay of nicotine in hair using MISPE provided a very selective and reliable method for the evaluation of the exposure to tobacco smoke.

Cotinine↗

PubMed2006

Predicting secretory protein signal sequence cleavage sites by fusing the marks of global alignments.

A newly synthesized secretory protein in cells bears a special sequence, called signal peptide or sequence, which plays the role of "address tag" in guiding the protein to wherever it is needed. Such a unique function of signal sequences has stimulated novel strategies for drug design or reprogramming cells for gene therapy. To realize these new ideas and plans, however, it is important to develop an automated method for fast and accurately identifying the signal sequences or their cleavage sites. In this paper, a new method is developed for predicting the signal sequence of a query secretory protein by fusing the results from a series of global alignments through a voting system. The very high success rates thus obtained suggest that the novel approach is very promising, and that the new method may become a useful vehicle in identifying signal sequence, or at least serve as a complementary tool to the existing algorithms of this field.

Algorithms↗

PubMed2006

Increased expression of endothelin B receptor in static stretch exposed porcine mitral valve leaflets.

The aim of this study was to evaluate the effect of mechanical stretch on the expression of ET-1 and ET(A)- and ET(B)-receptors in porcine mitral valve leaflets. Leaflet segments from 10 porcine mitral valves were exposed to a static stretch load of 1.5 N for 3.5h in buffer at 37 degrees C together with matching control segments. Subsequently, the mRNA expression of ET-1, ET(A)-R and ET(B)-R was measured by real-time RT-PCR in the chordal insertion areas. The analyses showed an increased transcription of ET(B)-receptors in stretch-exposed leaflet segments compared to unstretched segments median 2.23 (quartiles 1.37 and 2.70) vs. median 1.56 (quartiles 1.38 and 2.17, P=0.03) whereas the mRNA expression of ET(A)-receptors (P=0.90) and ET-1 (P=0.51) remained unchanged. Stretch increased the expression of ET(B)-receptors in porcine mitral valve leaflets. The finding could lead to a better understanding of the pathogenesis of myxomatous mitral valve disease.

Animals↗

PubMed2006

Menstrual cycle lengths and bone mineral density: a cross-sectional, population-based study in rural Chinese women ages 30-49 years.

INTRODUCTION: The menstrual cycle involves periodic fluctuations in estrogen and progesterone levels. Longer cycles have been associated with longer follicular phase, delayed estrogen peak and a lower mean oestradiol level of the entire cycle. METHODS: We hypothesized that prolonged menstrual cycle length is associated with decreased bone mineral density (BMD) in a population of pre- and perimenopausal women. This population-based cross-sectional study was conducted in rural Anhui province, China. It includes 4,771 women, aged 30 to 49 years, who did not smoke or drink alcohol, and did not use oral contraceptives or breastfeed during the previous year. Dual-energy X-ray absorptionometry (DEXA) BMD measurements were taken at four skeletal sites: whole body, total hip, femoral neck and lumbar spine. Menstrual cycle characteristics (polymenorrhea, short normal, long normal, oligomenorrhea, 90-day amenorrhea, irregular cycle) in the prior year were assessed by questionnaire. RESULTS: Prolonged menstrual cycle was consistently associated with decreased BMD at whole body, total hip, and femoral neck in both age 30-39, and age 40-49 stratum (p(trend)<0.05). Prolonged menstrual cycle was also associated with decreased lumbar spine BMD for women aged 40-49 (p(trend)<0.05). Among women with normal cycles aged 30-39, menstrual cycle length in the previous year was inversely associated with whole-body BMD (p<0.05). Women with 90-day amenorrhea had significantly lower mean total hip and femoral neck BMD relative to women with short normal cycles in the 30-39 age group; and had significantly lower whole body and total hip BMD relative to short normal cycles in the 40-49 age group. BMD in polymenorrheic women did not differ from BMD in women with short normal cycles at any of the skeletal sites. CONCLUSIONS: We conclude that prolonged menstrual cycle length is associated with decreased BMD in pre- and perimenopausal women in this population.

Adult↗

PubMed2006

Effect of pH on binding of mutagenic heterocyclic amines by the natural biopolymer poly(gamma-glutamic acid).

Poly(gamma-glutamic acid) (gamma-PGA), a nontoxic and biodegradable macropolymer, was evaluated for its efficiency in binding three mutagenic heterocyclic amines (HAs), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx), and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-p-2), as affected by pH in a batch mode. The maximum HA sorption was attained for pH 3-7 and decreased sharply for pH less than 3. Binding isotherms obtained at pH 2.5 and 5.5 showed different isotherm shapes that belong to S and L types, respectively. The isotherm data at pH 2.5 were well described by a linear form of the Langmuir equation, while at pH 5.5 it showed two distinct curves, which were precisely fitted as multiple Langmuir curves. The deviation of linearity in Scatchard plot proved the multisite HA sorption. The Brunauer-Emmett-Teller equation also fitted better to isotherm data at pH 5.5, suggesting a multisite sorption caused by multimolecular HA layers on gamma-PGA. High HA sorption levels of 1250, 667, and 1429 mg/g at pH 2.5 and 1429, 909, and 1667 mg/g at pH 5.5 were observed for MeIQ, 4,8-DiMeIQx, and Trp-p-2, respectively. Among the HAs studied, the sorption capacity correlated directly with hydrophobicity of HAs and inversely with the number of methyl groups in HA molecules. The plausible binding mechanism of HAs on gamma-PGA may include a combination of hydrophobic, hydrogen-bonding, ionic, and dipole-dipole interactions.

Adsorption↗

PubMed2006

Benzo(a)pyrene inhibits expression of inducible heat shock protein 70 in vascular endothelial cells.

Benzo(a)pyrene (BaP), a ubiquitous environmental pollutant known to cause many diseases including atherosclerosis, induces a dose-dependent reduction in the levels of the inducible Hsp70. To explore the mechanism underlying the reduction of Hsp70, we measured the levels of Hsp70, cytoplasmic and nuclear heat shock factor 1 (HSF1) in porcine aortic endothelial cells using Western blot, and then further characterized the binding ability of HSF1 and heat shock element (HSE) by electrophoretic mobility shift assay. We found that when porcine aortic endothelial cells were treated by 0.1-10 microM of BaP for 24 h, there was a significant reduction of Hsp70, cytoplasmic and nuclear HSF1 and the binding rate of HSF1 and HSE at 5, 10 microM of BaP but less effective at lower concentrations. The effect of BaP on the Hsp70 expression level was markedly attenuated by co-treatment with phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C (PKC). Staurosporine (STP), an inhibitor of PKC, blocked the effect of PMA treatment in combination with BaP. These results suggest that BaP might inhibit Hsp70 levels by reducing the expression of HSF1 and decreasing binding of HSF1 and HSE via PKC-dependent signaling pathways that might be involved in the regulation of Hsp70 gene expression under BaP.

Animals↗

PubMed2006

Hypoxia-inducible factor 1alpha cDNA cloning and its mRNA and protein tissue specific expression in domestic yak (Bos grunniens) from Qinghai-Tibetan plateau.

Adaptation to hypoxia is regulated by hypoxia-inducible factor 1 (HIF-1), a heterodimeric transcription factor consisting of an oxygen-regulated alpha-subunit and a constitutively expressed beta-subunit. How animals living on Qinghai-Tibetan plateau adapt to the extreme hypoxia environment is known indistinctly. In this study, the Qinghai yak, which has been living at 3000-5000 m altitude for at least two millions of years, was selected as the model of high hypoxia-tolerant adaptation species. The HIF-1alpha ORFs (open reading frames) encoding for two isoforms of HIF-1alpha have been cloned from the brain of the domestic yak. Its expression of HIF-1alpha was analyzed at both mRNA and protein levels in various tissues. Both its HIF-1alpha mRNA and protein are tissue specific expression. Its HIF-1alpha protein's high expression in the brain, lung, and kidney showed us that HIF-1alpha protein may play an important role in the adaptation to hypoxia environment.

Amino Acid Sequence↗

PubMed2006

Ultra-thin TLDs for skin dose determination in high energy photon beams.

Estimation of surface dose is very important for patients undergoing radiation therapy. In this work we investigate the dose at the surface of a water phantom and at a depth of 0.007 cm, the practical reference depth for skin as recommended by ICRP and ICRU, with ultra-thin TLDs and Monte Carlo calculations. The calculations and measurements were carried out for fields ranging from 5 x 5 cm2 to 20 x 20 cm2 for 6 MV, 10 MV and 18 MV photon beams. The variation of the surface dose with angle of incidence and field size was investigated. Also, the exit dose was computed and measured for the same fields and angles of incidence. The dose at the ICRU reference depth was computed. Good agreement (+/-5%) was achieved between measurements and calculations. The surface dose at the entrance increased with the angle of incidence and/or the field size. The exit dose decreased with the angle of incidence but it increased with field size. The dose at the surface of the patient is mostly dependent on the beam energy, modality and beam obliquity rather than the field size and field separation. By correlating TLD measurements with Monte Carlo calculations, we were able to predict the dose at the skin surface with good accuracy. Knowing the dose received at the surface of the patient can lead to prediction of skin reactions helping with the design of new treatment techniques and alternative dose fractionation schemes.

Breast Neoplasms↗

PubMed2006

Preparation of poly epsilon-caprolactone nanoparticles containing magnetite for magnetic drug carrier.

Magnetic poly epsilon-caprolactone (PCL) nanoparticles were prepared in a well shaped spherical form by the o/w emulsion method. The influence of some preparative variables on the size and surface property was investigated. Nanoparticles were smooth, well individualized and homogeneous in size. The presence of magnetite and its superparamagnetic characteristic were confirmed by transmission electron microscope (TEM), Fourier transform infrared spectroscopy (FT-IR) and vibrating sample magnetometer (VSM), respectively. The anti-cancer drug was encapsulated in the magnetic nanoparticle during preparation. A typical release behavior was observed for 30 days. In vitro experiment of magnetic susceptibility under external magnetic field demonstrated that the magnetic PCL nanoparticles have sufficient magnetic susceptibility for a potential magnetic drug carrier for targeted delivery.

Cisplatin↗

PubMed2006

Interaction of initiator proteins with the origin of replication of an IncL/M plasmid.

The origin of replication of the IncL/M plasmid pMU604 was analyzed to identify sequences important for binding of initiator proteins and origin activity. A thrice repeated sequence motif 5'-NANCYGCAA-3' was identified as the binding site (RepA box) of the initiator protein, RepA. All three copies of the RepA box were required for in vivo activity and binding of RepA to these boxes appeared to be cooperative. A DnaA R box (box 1), located immediately upstream of the RepA boxes, was not required for recruitment of DnaA during initiation of replication by RepA of pMU604 unless a DnaA R box located at the distal end of the origin (box 3) had been inactivated. However, DnaA R box 1 was important for recruitment of DnaA to the origin of replication of pMU604 when the initiator RepA was that from a distantly related plasmid, pMU720. A mutation which scrambled DnaA R boxes 1 and 3 and one which scrambled DnaA R boxes 1, 3 and 4 had much more deleterious effects on initiation by RepA of pMU720 than on initiation by RepA of pMU604. Neither Rep protein could initiate replication from the origin of pMU604 in the absence of DnaA, suggesting that the difference between them might lie in the mechanism of recruitment of DnaA to this origin. DnaA protein enhanced the binding and origin unwinding activities of RepA of pMU604, but appeared unable to bind to a linear DNA fragment bearing the origin of replication of pMU604 in the absence of other proteins.

Bacterial Proteins↗

PubMed2006

Downregulation of cAMP-dependent protein kinase inhibitor gamma is required for BMP-2-induced osteoblastic differentiation.

Osteoblasts, normally derived from undifferentiated mesenchymal precursor cells, acquire their characteristic phenotypes when induced by various regulatory factors, one of which is bone morphogenetic protein-2 (BMP-2). Our recent studies suggest that expression of cAMP-dependent protein kinase (PKA) inhibitor G (PKIG) is down-regulated as human mesenchymal stromal cells (MSCs) undergo BMP-2-induced osteoblastic differentiation. This raises our hypothesis that the PKA pathway is involved in osteogenesis. In this report, we demonstrated that PKIG in human MSCs and its murine homologue PKA inhibitor gamma (PKIgamma) in murine pre-myoblast C2C12 cells were down-regulated when these cells were treated with BMP-2. On the contrary, the PKA activity of C2C12 cells was increased upon BMP-2 treatment. Overexpression of PKIgamma in C2C12 cells was shown to repress mRNA expression of early osteoblastic markers osterix and type I collagen while inhibiting the PKA activity. This correlated with decreased alkaline phosphatase (ALP) activities. Furthermore, inhibition of the PKA activity using its specific inhibitor KT5720 was found to have the similar effect, whereas 8-Br-cAMP, a specific PKA activator, accelerated BMP-2-induced ALP activities. Finally, this study showed that BMP-2 treatment promoted activities of transcription regulatory elements including cAMP response element (CRE) and activating protein-1 (AP1). This effect of BMP-2 was diminished in PKIgamma-overexpressed C2C12 cells. Taken together, our results indicate that the activation of the PKA pathway may be one of key BMP-2-activated signaling events that lead to osteogenesis and that downregulation of PKIgamma may be prerequisite for the PKA activation during the osteoblastic differentiation of precursor cells.

Alkaline Phosphatase↗

PubMed2006

Modeling laser-generated guided waves in bonded plates by the finite element method.

The purpose of this research is to develop an effective model of the transient laser-generated guided waves in bonded plates by the finite element (FE) method. The FE parameters, such as the mesh density and the time step size, which are related to wave propagation, are optimized in order to set up a standard, and the correlation between these parameters is discussed. The waveforms in bonded plates with different bonded interface modeled by the spring model are obtained and then compared. The results show that the transient responses are sensitive to the stiffness coefficients characterizing the cohesive quality. Finally, these FE results are compared with analytical and experimental results. All these comparisons confirm the accuracy of the FE method for modeling laser-generated guided waves in bonded plates.

Journal Article↗

PubMed2006

A hybrid region-boundary model for cerebral cortical segmentation in MRI.

Automatic segmentation of cerebral cortex in magnetic resonance imaging (MRI) is a challenging problem in understanding brain anatomy and functions. The difficulty is mainly due to variable brain structures, various MRI artifacts and restrictive body scanning methods. This paper describes a hybrid model-based method for obtaining an accurate and topologically-preserving segmentation of the brain cortex. The approach is based on defining region and boundary information using, respectively, level set and Bayesian techniques, and fusing these two types of information to achieve cerebral cortex segmentation. It is automatic and robust to noise, intensity inhomogeneities, and partial volume effect. Another particularity of the proposed approach is that bias field is corrected during segmentation process and that the central layer of the cortex is accurately obtained through a topology correction step. The proposed method is evaluated on both simulated and real data, and compared with existing segmentation techniques. The obtained results have demonstrated its improved performance and robustness.

Algorithms↗

PubMed2006

Treatment of oesophageal ulcerations using endoscopic transplantation of tissue-engineered autologous oral mucosal epithelial cell sheets in a canine model.

BACKGROUND: With the recent development of endoscopic submucosal dissection (ESD), large oesophageal cancers can be removed with a single procedure, with few limits on the resectable range. However, after aggressive ESD, a major complication that arises is postoperative inflammation and stenosis that can considerably affect the patient's quality of life. AIMS: To examine a novel treatment combining ESD and the endoscopic transplantation of tissue-engineered cell sheets created using autologous oral mucosal epithelial cells, in a clinically relevant large animal model. METHODS: Oral mucosal epithelial cells, harvested from beagle dogs, were cultured under normal conditions at 37 degrees C, on temperature-responsive dishes. After ESD (5 cm in length, 180 degrees in range), cell sheets were harvested by a simple reduction in temperature to 20 degrees C, and transplanted by endoscopy. RESULTS: The transplanted cell sheets were able to adhere to and survive on the underlying muscle layers in the ulcer sites, providing an intact, stratified epithelium. Four weeks after surgery, complete wound healing, with no observable stenosis, was seen in the animals receiving autologous cell sheet transplantation. By contrast, noticeable fibrin mesh and host inflammation, consistent with the intermediate stages of wound healing, were observed in the control animals that received only ESD. CONCLUSIONS: These findings in a clinically relevant canine model show the effectiveness of a novel combined endoscopic approach for the potential treatment of oesophageal cancers that can effectively enhance wound healing and possibly prevent postoperative oesophageal stenosis.

Animals↗