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Biomedical subjects

Q Zhao

Publications and source records attributed to Q Zhao.

At least 19 recordsLinked to original sources

[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&#x2236;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&#xb1;15.71) years at screening. At Month 3, the mean diurnal IOP reduction from baseline was (6.56&#xb1;3.44) mmHg in the tafluprost/timolol group and (5.36&#xb1;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&#x2265;15%,&#x2265;25%, and&#x2265;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↗

Biochemical characterization of the zinc-finger protein 217 transcriptional repressor complex: identification of a ZNF217 consensus recognition sequence.

Zinc-finger protein 217 (ZNF217) is a Kruppel-like zinc-finger protein located at 20q13.2, within a region of recurrent maximal amplification. Here, we demonstrate that ZNF217 is a transcriptional repressor protein and report the purification and characterization of a ZNF217 complex. The purified ZNF217 complex consists of approximately six proteins and contains the transcriptional co-repressors CoREST, BHC110/LSD1, histone deacetylase (HDAC) 2 and C-terminal binding protein (CtBP1). The purified ZNF217 complex possesses deacetylase activity as well as lysine 4 histone H3-specific demethylase activity that is most likely mediated by the BHC110/LSD1 component. To determine if ZNF217 is a sequence-specific binding protein, we have made use of cyclic amplification and selection of targets (CAST) assay and identify for the first time a ZNF217 DNA consensus recognition sequence (CRS) that is highly conserved in the human E-cadherin promoter. Chromatin immunoprecipitation (ChIP) experiments demonstrate that ZNF217, as well as the other components of the ZNF217 complex, are found on the region of the proximal E-cadherin promoter that contains the identified ZNF217 CRS in vivo. Using a combination of transient transfections and small interfering RNA, we demonstrate that ZNF217 represses the E-cadherin promoter. Collectively, our results implicate ZNF217 and its associated proteins in a novel pathway that may have profound effects on cancer progression.

Base Sequence↗

Changes in the inferior alveolar nerve following sagittal split ramus osteotomy in monkeys: a comparison of monocortical and bicortical fixation.

We aimed to observe the changes in the inferior alveolar nerve (IAN) after bilateral sagittal split ramus osteotomy (SSRO) using monocortical or bicortical screw fixation. Bilateral SSRO for setback of the mandible was done in 12 monkeys, and monocortical or bicortical fixation was applied on opposing sides of each mandible. Sensory nerve action potentials were tested before and immediately after operation, and at 2, 4, 8, and 12 weeks. Six animals selected randomly were killed at 4 and 12 weeks after the operation. Specimens of nerve were harvested and processed for histological examination and electron microscopic analysis. Obvious prolongation of latency and diminution of amplitude in the IAN were found postoperatively. At 4 weeks after operation, Wallerian degeneration was apparent, and there were signs of axonal regeneration in the nerves. The IAN had more abnormalities of evoked potentials and pathological changes after bicortical than after monocortical fixation. Although considerable recovery was found after both forms of fixation at 12 weeks, the function of the nerve after plate fixation was better than after screw fixation. Our results suggest that the nerve damage during SSRO could be temporary and reversible, and monocortical fixation may result in restoration of the nerve function sooner than bicortical fixation.

Action Potentials↗

Designing and transgenic expression of melanin gene in tobacco trichome and cotton fiber.

In Streptomyces antibioticus, there are two genes TYRA and ORF438 required for the melanin biogenesis. To investigate whether expression of these two genes in cotton can change cotton fiber colour, we modified the TYRA and ORF438 genes to make their codon usage closer to the codon preference of cotton fiber genes. The resulting versions of these two genes were referred to as DTYRA and DORF438, respectively. Vacuolar targeting signals were also added to their ends. Under the cotton fiber specific LTP3 promoter, DORF438 and DTYRA were first transformed into model plant tobacco (Nicotiana tabacum). Molecular analyses showed that both the DORF438 and DTYRA genes were successfully expressed in transgenic plants, and the melanin deposition was observed in the trichomes of transgenic tobacco. Excitedly, when the same DORF438 and DTYRA expression cassettes were transformed into cotton (Gossypium hirsutum L.) by pollen tube pathway, the colour of cotton fiber changed from white to brown. Molecular analyses confirmed that both genes were transformed into cotton and expressed successfully. All these results indicate that the synthesized DOFR438 and DTYRA genes can work well in tobacco and cotton. Our study may provide a potential method for modifying the colour of cotton fiber.

Amino Acid Sequence↗

Laser-guided assembly of heterotypic three-dimensional living cell microarrays.

We have assembled three-dimensional heterotypic networks of living cells in hydrogel without loss of viability using arrays of time-multiplexed, holographic optical traps. The hierarchical control of the cell positions is achieved with, to our knowledge, unprecedented submicron precision, resulting in arrays with an intercell separation <400 nm. In particular, we have assembled networks of Swiss 3T3 fibroblasts surrounded by a ring of bacteria. We have also demonstrated the ability to manipulate hundreds of Pseudomonas aeruginosa simultaneously into two- and three-dimensional arrays with a time-averaged power <2 mW per trap. This is the first time to our knowledge that living cell arrays of such complexity have been synthesized, and it represents a milestone in synthetic biology and tissue engineering.

Biological Assay↗

Antileukemic roles of human phospholipid scramblase 1 gene, evidence from inducible PLSCR1-expressing leukemic cells.

Phospholipid scramblase 1 (PLSCR1) is a multiply palmitoylated protein which is localized in either the cell membrane or nucleus depending on its palmitoylated state. The increasing evidence showed the biological roles of PLSCR1 in cell signaling, maturation and apoptosis. To investigate the functions of PLSCR1 in leukemic cells, we generated an inducible PLSCR1-expressing cell line using myeloid leukemic U937 cells. In this cell line, PLSCR1 was tightly regulated and induced upon tetracycline withdrawal. Our results showed that inducible PLSCR1 expression arrested the proliferation of U937 cells at G1 phase. Meanwhile, PLSCR1-overexpressing U937 cells also underwent granulocyte-like differentiation with increased sensitivity to etoposide-induced apoptosis. Furthermore, we also found that PLSCR1 induction increased cyclin-dependent kinase inhibitors p27(Kip1) and p21(Cip1) proteins, together with downregulation of S phase kinase-associated protein 2 (SKP2), an F-box subunit of the ubiquitin-ligase complex that targets proteins for degradation. Additionally, PLSCR1 induction significantly decreased c-Myc protein and antiapoptotic Bcl-2 protein. Although the exact mechanism by which PLSCR1 regulates these cellular events and gene expression remains unresolved, our results suggest that PLSCR1 plays the antagonistic role regarding leukemia development. These data will shed new insights into understanding the biochemical and biological functions of PLSCR1 protein.

Apoptosis↗

Evidence for nucleon-resonance excitation in omega-meson photoproduction.

The photoproduction of the omega meson has been studied at GRAAL from threshold up to a photon energy of 1.5 GeV. The differential cross sections and beam asymmetries have been measured precisely at all angles. The total cross section is also obtained. Systematic enhancements of the differential cross section at large angles and nonzero beam asymmetries at intermediate angles provide clear evidence for s- and u-channel resonant processes. The data are compared to the results of hadron and quark models.

Journal Article↗

Surface free energy effect on bacterial retention.

Bacterial infection is one of the most frequent and severe complications in the long-term effectiveness of medical implants and devices, greatly increasing treatment cost and inconvenience to the patient. Surface physical and chemical properties are known to influence the extent and form of bacterial infection, although the exact correlation with specific properties is difficult due to the complexity of the system. One approach in the attempt to reduce the bacterial colonisation is to modify the surface energy and chemistry, so as to influence the interactions between the surface and the bacteria that come into contact with it. Five types of coatings were investigated in this study, together with silicone, and polished and non-polished stainless steel 316L. Surfaces were tested for retention of Pseudomonas aeruginosa AK1 after 1h. A good correlation (>90%) was found between P. aeruginosa AK1 retention and total surface free energy, as well as its polar and dispersive components. The minimum level of P. aeruginosa AK1 retention was found for a range of total surface free energy in the range 20-27 mN/m.

Bacterial Adhesion↗

DOTS in China - removing barriers or moving barriers?

In 1992, China initiated its modern National TB Control Programme (NTP) with DOTS strategy through a project funded by a World Bank loan. Key motives for the revised NTP-DOTS were to reduce financial barriers to patients by removing fee charges for diagnosis and treatment, and to address regressive suppliers' incentives for appropriate referrals. This study aims to assess to what extent China's NTP subsidies are achieving the objective of removing financial barriers to care in terms of patients' expenditure. One county with NTP-DOTS - Jianhu - and one county without - Funing - were selected. A cohort of 493 tuberculosis patients newly diagnosed in 2002 was interviewed by questionnaire. The main outcome measure was tuberculosis patients' expenditure on medical care and transportation/accommodation from the onset of symptoms to treatment completion. During the follow-up period, Funing started implementing NTP-DOTS, which offered a possibility of longitudinal comparison both between counties and within county. Ninety-four per cent (465/493) of subjects were followed-up. The mean total patient's expenditure on TB medical care and transportation/accommodation before TB diagnosis was higher in Jianhu than in Funing (715 vs. 256CNY), whereas it was higher in Funing (835 vs. 157CNY) after diagnosis. After implementing NTP-DOTS in Funing, expenditure after diagnosis decreased slightly whereas expenditure before diagnosis increased remarkably. We found that the market incentive structures in the reformed health system appear to have a stronger regressive effect and may result in prolonged delays before effective treatment can be given. We believe that doctors adapt to new incentive structures, with bonus income being linked to the hospitals' fee-for-service revenue, and find new ways of keeping revenue at the old levels, which reduce or eliminate the intended effect of the subsidies. TB patients suffer a heavy economic burden even in counties where NTP-DOTS treatment is subsidized. The total patient expenditure was reduced only marginally, but shifted substantially from after diagnosis to before diagnosis. The shift could imply delays in diagnosis and treatment with an increased risk of infection transmission.

Adolescent↗

Erythroid differentiation denucleation factors (EDDFs) function as intrinsic, post-erythropoietin regulators for mammalian erythroid terminal differentiation.

Regulatory factors other than erythropoietin (Epo) dependence, that control mammalian erythroid terminal differentiation, are currently uncertain. Here we report the existence of erythroid differentiation factors in erythroid cytoplasm. Purification of these factors from cultured Friend virus anaemia (FVA)-infected mouse splenic erythroblasts was carried out using isoelectrophoresis and high performance of liquid chromatography techniques. We have identified intracellular erythroid differentiation denucleation factors (EDDFs) that were able to mediate the events of post-Epo-dependent erythroblast terminal differentiation. Purified EDDF proteins bound specifically to the enhancer HS2 sequence of the globin gene activated the expression of haemoglobin in mouse erythroleukaemia and K562 erythroleukaemic cells and promoted them to differentiate into mature erythrocytes. EDDF proteins began to emerge at the pro-early erythroblast stages upon exposure to Epo in culture, and increased dramatically in early erythroblast stage. The dynamic of EDDF expression and its action on the key events of erythroblast differentiation and denucleation appeared to be closely consistent with its spatiotemporal distribution. These results suggest that EDDFs are the critical intracellular regulatory factors that may act as the successive regulators to Epo, responsible for the final stages of erythroid terminal differentiation.

Activins↗

MRI-guided, open trial of abciximab for ischemic stroke within a 3- to 24-hour window.

The authors assessed the effect of IV abciximab on early neurologic improvement and ischemic lesion growth in 29 patients with supratentorial stroke and NIH stroke scale score (NIHSSS) > or = 4 (11.1 +/- 5.9), treated within 3 to 24 (13.6 +/- 5.5) hours of onset. The 48 to 72-hour NIHSSS improvement was 4.4 +/- 3.2 and the 24-hour lesion growth on DWI was +23% (-50%, +103%); 7/26 (27%) patients experienced lesion size decrease. Treatment of sub-24-hour stroke with abciximab improves early post-treatment neurologic status and often attenuates ischemic lesion growth.

Abciximab↗

Influence of surface energy of modified surfaces on bacterial adhesion.

There are a number of contrary reports on the effect of surface energy of substrates on bacterial adhesion. Some reports showed that bacterial adhesion decreased with decreasing surface energy of substrates; while other reports showed that bacterial adhesion decreased with increasing surface energy of substrates. In this study Escherichia coli adhesion on the Ni--P--PTFE coatings with various surface energies was investigated and the extended DLVO theory was used to calculate the interaction energy between bacteria and the substrates in water. The theory explained the effect of surface energy of substrates on bacterial adhesion.

Bacterial Adhesion↗

Carbon nanotube-metal cluster composites: a new road to chemical sensors?

Novel carbon nanotube-metal cluster structures are proposed as prototype systems for molecular recognition at the nanoscale. Ab initio calculations show that already the bare nanotube cluster system displays some specificity because the adsorption of ammonia on a carbon nanotube-Al cluster system is easily detected electrically, while diborane adsorption does not provide an electrical signature. Since there are well-established procedures for attaching molecular receptors to metal clusters, these results provide a "proof-of-principle" for the development of novel, high-specificity molecular sensors.

Ammonia↗

Radioprotection by fullerenols of Stylonychia mytilus exposed to gamma-rays.

The aim was to study the protective effects of fullerenols, C60(OH)x, on Stylonychia mytilus cells exposed to 60Co gamma-rays and the probable mechanisms of fullerenols protection. Ciliated protozoans Smytilus, kept in solutions of fullerenols at different concentrations, were irradiated with 60Co gamma-rays to various dose levels. Surviving cells were counted each day over 5 days after irradiation, and the surviving fraction was calculated. The relations of the surviving fraction to radiation dose and to fullerenols concentration were studied. Superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA) and lipofusion (LIP) levels in S. mytilus were also measured. The surviving fraction of S. mytilus decreased with increasing gamma-ray doses from 100 to 2000 Gy. Fullerenols enhanced the surviving fraction, except for the highest gamma-ray dose level. The maximum protection by fullernols occurred at a concentration of 0.10 mg ml(-1). However, fullerenols at concentration of 0.25 mg ml(-1) yielded a surviving fraction lower than that for the control sample. Fullerenols at a concentration of 0.10 mg ml(-1) increased the SOD and CAT activities in the gamma-ray plus fullerenols (gamma + F) group compared with the levels in both the gamma-ray (gamma) group (p < 0.01) and the control group (p < 0.01). The MDA and LIP levels in the gamma + F groups (p < 0.01) were significantly lower than that in both the control group (p < 0.05) and the gamma group (p < 0.01). At a concentration of 0.25 mg ml(-1), fullerenols reduced the SOD and CAT activities, but increased the MDA and LIP level compared with the control. There was no significant difference in SOD and CAT activities between the gamma + F group and gamma group. While the MDA and LIP level in the gamma + F and gamma groups were similar at a dose of 500 Gy, the LIP level in the gamma + F group was significantly higher than that in the gamma group (p < 0.01) at a dose of 2000 Gy. Fullerenols are good radiation protectors for the protozoan S. mytilus exposed to gamma-rays. The effectiveness of radioprotection depends on both fullerenols concentration and gamma-ray dose. The protective effect of fullerenols on damage induced by gamma-rays seems to be mediated, at least in part, through their anti-oxidative and radical scavenging activities.

Animals↗

Effect of temperature on the surface free energy of amorphous carbon films.

Diamond-like carbon (DLC) and tetrahedral amorphous carbon (ta-C) have attracted much attention recently for biomedical and antifouling applications due to their excellent biocompatibility and inherent nonstick properties. It has been demonstrated that the solid surface free energy is a dominant factor in cellular or fouling adhesion. However, few data for the surface free energy of DLC and ta-C coatings at temperatures in the range 37-95 degrees C are available. In this study DLC and ta-C coatings on stainless steel 304 sheets were prepared using an unbalanced magnetron sputtering system and a filtered cathodic vacuum arc system, respectively. The contact angles of water, diiodomethane and ethylene glycol on the coated surfaces at temperatures in the range 20-95 degrees C were measured using a Dataphysics OCA-20 contact angle analyzer. The surface free energy of the coatings and their components (e.g., dispersion, polar or acid/base portions) were calculated using various methods. The experimental results showed that the total surface free energy and dispersive surface free energy of the ta-C coatings, DLC coatings, stainless steel 304 and titanium decreased with increasing surface temperature, while the acid-base SFE component increased with increasing temperature.

Journal Article↗

Inhibition of neointimal hyperplasia after balloon injury by cis-element 'decoy' of early growth response gene-1 in hypercholesterolemic rabbits.

Early growth response factor-1 (Egr-1) is a transcription factor that is rapidly activated after vascular injury and thus might contribute to vascular proliferation and inflammation. We hypothesized that Egr-1 might therefore be a therapeutic target against restenosis. Hypercholesterolemic rabbits were intraluminally administered synthetic DNA as a 'decoy' against Egr-1 immediately after carotid artery balloon injury. Efficient transfection was confirmed by the delivery of a fluorescence-labeled decoy. Gel mobility-shift assay showed increased Egr-1 activity after balloon injury and its prevention by Egr-1 decoy transfection in vivo. Egr-1 decoy transfection attenuated early inflammation and proliferation and later neointimal hyperplasia. In addition, Egr-1 decoy transfection reduced gene expression and protein production of Egr-1-dependent genes such as platelet-derived growth factor-B, transforming growth factor-beta1, and monocyte chemoattractant protein-1. The Egr-1 pathway has an essential role in the pathogenesis of neointimal hyperplasia after balloon injury in hypercholesterolemic rabbits. This decoy strategy is a potential practical form of therapy for human restenosis.

Angioplasty, Balloon↗

Rapid induction of cAMP/PKA pathway during retinoic acid-induced acute promyelocytic leukemia cell differentiation.

The second messenger cyclic adenosine monophosphate (cAMP) plays an important role in cell proliferation, differentiation and apoptosis. In the present work, we evaluated the cAMP signaling in acute promyelocytic leukemia (APL) cells in the context of differentiation induced by all-trans retinoic acid (ATRA). There was a marked increase in the intracellular cAMP level within a few minutes after treatment with ATRA in APL cell line NB4 and fresh APL cells, whereas no such phenomenon was observed in NB4-R1 cells that are resistant to ATRA-induced maturation. In addition, the basal level of intracellular cAMP was lower in NB4-R1 than in NB4 cells. Mechanistic study showed that this induction of cAMP was mediated through the activation of adenylate cyclase. Moreover, we found that cAMP-dependent protein kinase (PKA) activity was quickly upregulated in parallel in ATRA-treated NB4 cells, and the phosphorylation of RARalpha by PKA could increase its transactivation effect. Use of H-89, an inhibitor of PKA, could partially suppress the transcriptional expression of ATRA target genes and ATRA-induced differentiation of APL cells. Taken together, we suggested a crosstalk between ATRA-induced cytosolic pathway and nuclear pathway in APL cell differentiation.

Adenylyl Cyclases↗