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Biomedical subjects

Mei Zhang

Publications and source records attributed to Mei Zhang.

At least 91 records · Page 5Linked to original sources

Stimulation of P2X7 receptors elevates Ca2+ and kills retinal ganglion cells.

PURPOSE: Retinal ganglion cells are known to express ionotropic P2X(7) receptors for ATP. Stimulation of these receptors in other cells can elevate Ca(2+) and sometimes lead to cell death. This study asked whether P2X(7) receptor stimulation alters the Ca(2+) levels and viability of retinal ganglion cells. METHODS: P2X(7) agonists were applied to retinal ganglion cells from neonatal rats loaded with fura-2 to examine their effect on intracellular Ca(2+) levels. The effect of P2X(7) receptor stimulation on cell viability was examined in rat retinal ganglion cells back-labeled with aminostilbamidine. RESULTS: The P2X(7) agonist benzoylbenzoyl adenosine triphosphate (BzATP) led to a large, sustained increase in Ca(2+). BzATP was >100-fold more effective than ATP at raising intracellular Ca(2+), when both agonists were applied at 10 microM. The response to BzATP was enhanced threefold by removal of extracellular Mg(2+), was dependent on extracellular Ca(2+), and was prevented by brilliant blue G (BBG). BzATP led to a concentration-dependent reduction in the number of cells with a median lethal dose (LD(50)) of 35 muM. Cell death was prevented by the P2X(7) antagonists BBG and oxidized ATP, but not by 30 microM suramin, consistent with the actions of the P2X(7) receptor. BzATP activated caspases in ganglion cells, but did not lead to membrane blebbing or increased permeability to Yo-Pro-1. The L-type Ca(2+) channel blocker nifedipine attenuated cell death, suggesting excessive Ca(2+) influx contributes to the lethal effects of BzATP. CONCLUSION: Short-term stimulation of the P2X(7) receptor can raise Ca(2+) in rat retinal ganglion cells, whereas sustained stimulation of the receptor can kill them.

Adenosine Triphosphate↗

Construction and identification of Fas-targeting siRNA-expressing plasmid.

OBJECTIVE: To study the therapeutic potential of Fas inhibition in different diseases, a Fas-targeting siRNA (small interfering)-expressing plasmid was constructed. METHODS: The U6 promoter cassette and siFas (small interfering RNA that inhibit Fas expression) template sequence were obtained by PCR method. They were cloned into modified pcDNA3.1. The resultant plasmid pU6-siFas was transfected into P815 cells with lipofectin2000 and selected under G-418-containing culture medium. Fas inhibition in stably transfected cells was detected by immunocytochemistry. RESULTS: The plasmid pU6-siFas efficiently reduced the expression of Fas and conferred G-418 resistance in P815 cells. CONCLUSION: The successful construction of the siRNA expressing plasmid will facilitate the application of RNA interference technique and lay the foundation for further study of Fas inhibition in the treatment of different diseases such as aplastic anemia and acute liver failure.

Animals↗

[Selection of peritoneal dialysis schemes based on multi-objective fuzzy pattern recognition].

The fuzziness in the selection of peritoneal dialysis schemes is discussed. A method of multi-objective fuzzy pattern recognition and its application in the selection of peritoneal dialysis schemes are presented. The method was first applied to the field of peritoneal dialysis. The conclusion showed that this method agreed with doctors' opinions. It provides a new idea for research in this field. At the same time, since the method is simple and easy to use, it can be of wide application.

Fuzzy Logic↗

[Induction of active antitumor immune response by myeloma idiotype protein-pulsed dendritic cells].

BACKGROUND & OBJECTIVE: Most multiple myeloma (MM) patients could not be cured by high-dose chemotherapy and bone marrow transplantation. This study was designed to investigate in vitro killing effect of tumor-specific cytotoxic T lymphocytes (CTLs) stimulated by idiotype protein (Id)-pulsed dendritic cells (DCs) on autologous MM cells. METHODS: DCs were generated from peripheral blood monocytes of 6 MM patients using interleukin-4 (IL-4) and granulocyte-macrophage colony-stimulating factor (GM-CSF). After cultured for 5 days, immature DCs were pulsed with Idû tumor necrosis factor-alpha (TNF-alpha) was added at the 7th day. Id-pulsed DCs were cocultured with autologous T cells for 3 days to induce tumor-specific CTLs. MTT assay was used to detect proliferation of autologous T cells, and evaluate killing effect of CTLs on autologous MM cells. RESULTS: Mature DCs were successfully induced. Id-pulsed DCs markedly increased proliferation of autologous T cells in a dose-dependent manner; stimulation index (SI) of Id-pulsed DCs was the highest [(39.1+/-6.0)%] when the radio of DCs to T cells was 10:1, which was significantly higher than those of unpulsed mature DCs [(19.3+/-7.7)%], Id-pulsed immature DCs [(15.9+/-6.1)%], and unpulsed immature DCs [(11.4+/-4.9)%] (P < 0.01). Id-pulsed DCs induced anti-MM activity of CTLs in a dose-dependent manner. Unpulsed mature DCs also induced cytotoxicity of CTLs against autologous MM cellsû however, when DC:T was 30:1, killing rate of MM cells was significantly higher in Id-pulsed mature DCs group than in unpulsed mature DCs group [(70.1+/-7.9)% vs. (40.8+/-7.8)%,P < 0.05]. KRN7000-pulsed mature DCs stimulated proliferation of allogeneic T cells in a dose-dependent manner; when DC:T was 1:10, SI was significantly higher in KRN7000-pulsed mature DCs group than in unpulsed mature DCs group [(38.5+/-5.7)% vs. (20.2+/-5.7)%, P < 0.05]. CONCLUSIONS: Mature DCs could be induced and Id with biological activity could be extracted from peripheral blood of MM patients. Id-pulsed DCs could induce antitumor immune response. KRN7000 could improve the immune function of in vitro cultured DCs.

Adult↗

[Ocular manifestations in HIV/AIDS].

Since the first case of acquired immunodeficiency syndrome (AIDS) was diagnosed in 1981, the number of cases of human immunodeficiency virus (HIV) infection has been continuously increasing around the world. In China, HIV/AIDS is spreading through out the whole country in a surprising speed. Therefore, understanding HIV/AIDS as much as possible has been the responsibility for every health care worker in China. In the present review, we present the key ocular manifestations of HIV/AIDS, mostly focusing on the clinical features and therapies of the posterior segment complications, including HIV retinitis, opportunistic infection, rare tumor and neuro-ophthalmological manifestations. Brief introduction to the following topics will also be also given in this review, including the anterior segment manifestations in HIV/AIDS, the ocular characteristics of HIV/AIDS in the developing countries, and the major procedures of HIV/AIDS prevention during clinical practice.

Acquired Immunodeficiency Syndrome↗

[The medicinal serum of yi-shen ruan-jian san antagonized the effect of aristolochic acid on human proximal tubular epithelial cells in vitro].

OBJECTIVE: To evaluate whether the medicinal serum of Yi-shen Ruan-jian san can antagonize the fibrogenic effect of human proximal tubular epithelial cell line (HKC) activated by aristolochic acid (AA) in vitro. METHOD: The HKC was incubated in the media containing 40 mg x L(-1) aristolochic acid sodium salt (AA-Na) with or without 10% concentration of Yi-shen Ruan-jian san medicinal serum. Then the cell proliferation and cytotoxicity of HKC were determined by MTF and lactate dehydrogenase (LDH) release assay respectively, the antigen expression of cytokeratin and alpha-smooth muscle actin on HKC was detected by immunocytochemistry, the mRNA expression of transforming growth factor-beta1 (TGF-beta1), connective tissue growth factor (CTGF), plasminogen activator inhibitor-1 (PAI-1), tissue inhibitor of metalloproteinase-1 (TIMP-1) and type I Collagen (Col I) of HKC was measured by RT-PCR, and their protein expression was measured by ELISA or Western blot. RESULT: No cytotoxic effect was found in HKC after stimulation of AA-Na with or without the medicinal serum of Yi-shen Ruan-jian san (P > 0.05). No epithelial-myofibroblast transdifferentiation was found in HKC after AA-Na stimulation. The mRNA and protein expression of TGF-beta1, CTGF, PAI-1 and TIMP-1 of HKC was significantly upregulated by AA-Na (P < 0.05). The above-mentioned enhanced mRNA and protein expression, except for PAI-1, was significantly downregulated by the medicinal serum of Yi-shen Ruan-jian san, compared with the control (normal rat serum in the same concentration) (P < 0.05). CONCLUSION: The fibrogenic effects of HKC activated by AA are antagonized by Yi-shen Ruan-jian san, through downregulating the expression of promoting excellular matrix (ECM) synthesis factors (TGF-beta1, CTGF) and inhibiting ECM degradation factor (TIMP-1).

Animals↗

[Analysis on the complications of hysteroscopic surgeries].

OBJECTIVE: To investigate the causations, management and prevention methods on the complications of hysteroscopic procedures. METHODS: Retrospective analysis of 36 cases with hysteroscopic complication, focusing on their characteristics and clinical management as well as prevention methods during the ten years from 1993 to 2004. RESULTS: Among 36 cases, 11 cases with uterine perforation and incomplete perforation, which happened during the complicated procedures, were treated by both laparoscopy and laparotomy. Five cases with heavy bleeding were encountered because of the deeply injury to the uterine wall and Foley catheter was inserted into uterine cavity and it stopped the bleeding successfully except in one case done by hysterectomy. Three cases with fluid overload syndrome were cured by using diuretic agent and saline infusion. There is no serious consequence in one case with air embolism due to prompt diagnosis and treatment. Four cases with postablation-sterilization syndrome were treated effectively by performing hysterectomy plus single or bilateral salpingectomy, dilating cervical canal as well as resecting adhesions. Twelve cases with adhesion inside uterine cavity followed hysteroscopy were also treated by dilating cervical canal, underwent adhesionlysis and hysterectomy. CONCLUSIONS: The potential factors causing complications of hysteroscopy include complicated procedures inside uterine cavity, higher pressure of irrigation, deep injury of endometrium as well as incomplete removal of endometrium during hysteroscopic operations. It is the necessary measures to reduce the complications by performing laparoscopy or B ultrasound monitoring simultaneously, standardizing the procedure and strengthening postoperation management.

Endometrium↗

[Effect of doxycycline on inflammation-related cytokines and apoptosis in human conjunctival epithelial cells].

OBJECTIVE: To evaluate the effects of doxycycline on the regulation of intercellular adhesion molecule-1 (ICAM-1, CD54), interleukin-1beta (IL-1beta), human leukocyte antigen DR (HLA-DR) and apoptosis in human conjunctival epithelial cells. METHODS: Human primary conjunctival epithelial cells were isolated and cultured from donors and identified by immunohistochemistry. Cultured epithelial cells were treated with either 0 U/ml IFN-gamma, 300 U/ml IFN-gamma, 300 U/ml IFN-gamma with 10 microg/ml doxycycline, 300 U/ml IFN-gamma with 20 microg/ml doxycycline, 300 U/ml IFN-gamma with 40 microg/ml doxycycline or 300 U/ml IFN-gamma with 100 microg/ml dexamethasone for 24 hours. The amount of CD54, HLA-DR and IL-1beta was measured by flow cytometry and western blot analysis. Apoptosis was evaluated by flow cytometry after the cultured epithelial cells were treated for 72 hours. RESULTS: Cultured conjunctival epithelial cells can express CD54 and IL-1beta. IFN-gamma increased the amount of CD54 and IL-1beta (P < 0.01). Doxycycline and dexamethasone inhibited the IFN-gamma induced increase of express of CD54 and IL-1beta of cultured conjunctival epithelial cells, and the inhibiting effect was dependent on the concentration of doxycycline (P < 0.01). Very little HLA-DR and apoptosis were detected before and after treatment with IFN-gamma. CONCLUSION: Doxycycline can suppress the expression of inflammatory cytokine such as CD54 and IL-1beta, which suggests that doxycycline may be a potent drug for the treatment of ocular surface inflammatory disease.

Anti-Bacterial Agents↗

[Effects of Danshen injection on the reserve of tissue plasminogen activator and nitric oxide in endothelium and vasodilatation in diabetic patients].

OBJECTIVE: To investigate the effects of Danshen Injection on the reserve of tissue plasminogen activator and nitric oxide in endothelium and vasodilatation in diabetic patients. METHODS: 32 patients and 16 normal individuals were enrolled into this study. The capacity of vascular endothelium to release tPA and NO was examined by venous occlusion of the upper arm. Brachial artery diameter was measured at baseline, during post occlusion reactive hyperemia (flow-mediated endothelium-dependent), and after sublingual nitroglycerol administration (endothelium-independent). Vasodilation was expressed as the percentage changes relative to the baseline diameter, while endothelial tPA and NO release was expressed as the percentage change relative to the baseline tPA and NO levels. Thickness of the intima of carotid artery was measured using ultrasound imaging. RESULTS: There was no significant difference in eudothelum-independent vasodilation between the controls and diabetes. However, significant reduction in endothelium-dependent vasodilation, endothelial NO release and tPA release (P <0.05, or P <0.01) were found in diabetes compared with the controls and the reduction was lower in diabetes with hypertension than that in diabetes without it. At the same time, there was no difference in intimamedial thickness of the carotid artery between two groups, although the carotid artery in the diabetes without hypertension was much thicker than that in the control. But that in the diabetes with hypertension had significant difference compared with that in the control. CONCLUSION: Danshen Injection may improve the above-mentioned marks. And it may increase the endothelium-dependent vasodilation and endothelial tPA and NO release and improve the vascular disease in patients with diabetes mellitus.

Adult↗

[Effects of lactone I from Atractylodes macrocephala Koidz on cytokines and proteolysis-inducing factors in cachectic cancer patients].

OBJECTIVE: To observe the effect of lactone I from Atractylodes macrocephala Koidz (LAMK I) on the cytokines and proteolysis-inducing factors (PIF) in cachectic cancer patients. METHOD: Sixty-four cachectic cancer patients were randomized into two groups, namely LAMK I group and FOE (fish oil-enriched nutritional supplementation) treatment group. The appetite, body weight changes, mid-arm muscle circumference (MAMC), and KPS scores were recorded 3 and 7 weeks after the treatment. Immunohistochemistry was used to analyze the changes in the cytokines interleukin (IL)-1, IL-6 and tumor necrosis factor (TNF)-alpha and Western blotting employed to examine the changes of PIF after the treatment. RESULTS: The patients' appetite and MAMC in LAMKI group was better than those of patients in FOE group, and the serum IL-1 and TNF-alpha levels and urine PIF level were significantly lower than those of FOE group. Body weight and serum IL-6 level were not significantly different between the two groups. CONCLUSION: Lactone I from Atractylodes macrocephala Koidz can be beneficial for treating cancer cachexia.

Adult↗

[Comparable analysis of in-hospital mortality in patients with acute myocardial infarction].

OBJECTIVE: To investigate the change of the mortality of AMI and influence factors within 20 years. METHODS: Clinic data of 134 AMI patients from 1980 to 1983, 354 AMI patients from 1990 to 1993 and 817 AMI patients from 2000 to 2003 were comparably analyzed. RESULTS: In hospital mortality of AMI was 22.4% from 1980 to 1983, 14.4% from 1990 to 1993 and 9.2% from 2000 to 2003, respectively (P < 0.01). The decrease of in-hospital mortality in male was more significant than in female (P < 0.01). The corresponding factors for decrease of mortality were younger than 60 years old, first onset of AMI, successful rescue of cardiac arrest and reperfusion management of infarction relative artery. The disadvantage factor was female. CONCLUSIONS: Improvement of medical and reperfusion management of AMI conduced in significant decreases of hospital mortality.

Adrenergic beta-Antagonists↗

[Construction of FAS-targeted RNAi-retroviral vector and its identification for biological activity].

This study was aimed to construct mouse Fas-targeting si RNA-expressing recombinant retroviral vector in order to explore the therapeutic potential of Fas inhibition by siRNA in the treatment of aplastic anemia and to provide a basia for extensive development of RNA interference techninque. The U6(+) 27 promoter cassette and siFas sequence were obtained by PCR method. The U6-siFas fragment was cloned into the multiple restriction site of pLXSN-EGFP and directly downstream of EGFP gene. The resultant retroviral vector pLXSN/EGFP-siFas was packaged using PA317 cell line and tittered using NIH3T3 cell line. P815 cells were infected by the retroviral vector. EGFP expression in P815 was observed under fluorescent microscope and Fas inhibition effect was detected by immunohistochemistry. The results indicated that successfully constructed retrovirus vector pLXSN/EGFP-siFas was could not only deliver siRNA into mammalian cells efficiently and inhibit Fas expression in P815 cells, but also could express EGFP as marker and neomycine resistance gene to allow antibiotic selection. It is concluded that the successful construction of this retroviral vector would greatly facilitate the application of RNA interference and lay the foundation for therapeutic study of Fas inhibition in the treatment of aplastic anemia.

Anemia, Aplastic↗

[Seroepidemiology study on Helicobacter pylori (cagA, vacA) infection of elderly people in Beijing].

OBJECTIVE: To assess the prevalence rate of Helicobacter pylori (H. pylori) in blood serum, its affecting factors and isoforms (CagA,VacA )infection in the elderly people in Beijing. METHODS: 2006 residents were investigated through household questionnaire in different areas of Beijing (urban, suburban and mountainous district), who were older than 60 years old. Serum H. pylori CagA, VacA and Ureas antibody was detected by immunoblotting. RESULTS: The total H. pylori infection rate was 83.4% and the infectious rate of I form pathogenic H. pylori was 56.0%. The incidence rate in urban or suburban district was higher than that of in mountainous district (P < 0.001). I form H. pylori infection rate in people with heavy labor or young elderly were higher than that of intelegent work or older elderly (P < 0.05 ). I form H. pylori infection rate in people of low diet was higher than that of high protein diet (P < 0.001). CONCLUSION: The rate of H. pylori infection in blood serum was high among the elderly people in Beijing with most of it belonged to type I . However, significant differences were noticed on the distribution of isoforms in different age groups, areas, professions and diet habit.

Age Distribution↗

[In vitro anti-myeloma effects induced by myeloma idiotype-protein pulsed dendritic cell vaccine].

OBJECTIVE: To investigate the specific antitumor immune response induced by idiotype protein (Id)-pulsed dendritic cells (DC) in vitro. METHODS: DC was generated from peripheral blood monocytes of the multiple myeloma (MM) patients using GM-CSF, IL-4, and TNF-alpha. The DCs were pulsed with idiotypic fragment, the F(ab')2 fragment of M protein from MM patient at the immature stage. The morphologic characteristics of the cells were observed with light and electron microscopes. The phenotypic features were analyzed with FACS, MTT assay was employed to evaluate the proliferation of autologous T cells and the inhibition rate of MM cells. RESULTS: DC precursors in peripheral blood could be induced to typical mature DC in medium containing GM-CSF, IL-4 and TNF-alpha. Mature DC with Id could increase the proliferation of the autologous T cells and activate naive T cells to become tumor specialized cytotoxic T lymphocytes (CTL). The CTL at different doses showed significant inhibition on or killing ability to autologous MM cells in vitro. CONCLUSIONS: In a suitable cytokine environment, the DC precursors from peripheral blood of MM patients could be induced to functional DC, and vaccination of Id-pulsed DC could induce active antitumor immune response.

Adult↗

Angioblasts in adult and its role in ocular disorders due to neovascularization.

Blood vessel formation includes vasculogenesis and angiogenesis. Traditionally vasculogenesis is believed to occur in embryo, forming blood vessels by the differentiation of angioblasts, while angiogenesis is defined as the formation of new blood vessels that originate from pre-existing vessels, which happens both in embryo and adult. However, recent studies on angioblasts have shown that new blood vessel formation due to angioblast differentiation, once was believed to happen exclusively in embryo, also occurs in adult. These findings not only help us to understand the pathogenesis of new blood vessel formation, but also provide some new clues to investigate new therapeutic target for the treatment of angiogenesis.

Adult↗

The phosphatidylglycerol/cardiolipin biosynthetic pathway is required for the activation of inositol phosphosphingolipid phospholipase C, Isc1p, during growth of Saccharomyces cerevisiae.

Inositolsphingolipid phospholipase C (Isc1p) is the Saccharomyces cerevisiae member of the extended family of neutral sphingomyelinases that regulates the generation of bioactive ceramides. Recently, we reported that Isc1p is post-translationally activated in the post-diauxic phase of growth and that it localizes to mitochondria (Vaena de Avalos, S., Okamoto, Y., and Hannun, Y. A. (2004) J. Biol. Chem. 279, 11537-11545). In this study the in vivo mechanisms of activation and function of Isc1p were investigated. Deletion of ISC1 resulted in markedly lower growth in non-fermentable carbon sources. Interestingly, the growth defect of isc1Delta strains resembled that of pgs1Delta strains, lacking the committed step in the synthesis of phosphatidylglycerol (PG) and cardiolipin (CL), which were shown to activate Isc1p in vitro. Therefore, the role of Pgs1p in activation of Isc1p in vivo was investigated. The results showed that in the pgs1Delta strain, the growth-dependent activation of Isc1p was impaired as was the ISC1-dependent increase in the levels of phytoceramide during the post-diauxic phase, demonstrating that the activation of Isc1p in vivo is dependent on PGS1 and on the mitochondrial phospholipids PG/CL. Mechanistically, loss of Isc1p resulted in lower levels of mitochondrial cytochrome c oxidase subunits cox3p and cox4p, previously established targets of both PG and CL (Ostrander, D. B., Zhang, M., Mileykovskaya, E., Rho, M., and Dowhan, W. (2001) J. Biol. Chem. 276, 25262-25272), thus suggesting that Isc1p mediates at least some functions downstream of PG/CL. This study provides the first evidence for the mechanism of in vivo activation and function of Isc1p. A model with endogenous PG/CL as the in vivo activator of Isc1p is proposed.

CDPdiacylglycerol-Serine O-Phosphatidyltransferase↗

Multifunctional carbon nanotube yarns by downsizing an ancient technology.

By introducing twist during spinning of multiwalled carbon nanotubes from nanotube forests to make multi-ply, torque-stabilized yarns, we achieve yarn strengths greater than 460 megapascals. These yarns deform hysteretically over large strain ranges, reversibly providing up to 48% energy damping, and are nearly as tough as fibers used for bulletproof vests. Unlike ordinary fibers and yarns, these nanotube yarns are not degraded in strength by overhand knotting. They also retain their strength and flexibility after heating in air at 450 degrees C for an hour or when immersed in liquid nitrogen. High creep resistance and high electrical conductivity are observed and are retained after polymer infiltration, which substantially increases yarn strength.

Journal Article↗

Gating charges in the activation and inactivation processes of the HERG channel.

The hERG channel has a relatively slow activation process but an extremely fast and voltage-sensitive inactivation process. Direct measurement of hERG's gating current (Piper, D.R., A. Varghese, M.C. Sanguinetti, and M. Tristani-Firouzi. 2003. PNAS. 100:10534-10539) reveals two kinetic components of gating charge transfer that may originate from two channel domains. This study is designed to address three questions: (1) which of the six positive charges in hERG's major voltage sensor, S4, are responsible for gating charge transfer during activation, (2) whether a negative charge in the cytoplasmic half of S2 (D466) also contributes to gating charge transfer, and (3) whether S4 serves as the sole voltage sensor for hERG inactivation. We individually mutate S4's positive charges and D466 to cysteine, and examine (a) effects of mutations on the number of equivalent gating charges transferred during activation (z(a)) and inactivation (z(i)), and (b) sidedness and state dependence of accessibility of introduced cysteine side chains to a membrane-impermeable thiol-modifying reagent (MTSET). Neutralizing the outer three positive charges in S4 and D466 in S2 reduces z(a), and cysteine side chains introduced into these positions experience state-dependent changes in MTSET accessibility. On the other hand, neutralizing the inner three positive charges in S4 does not affect z(a). None of the charge mutations affect z(i). We propose that the scheme of gating charge transfer during hERG's activation process is similar to that described for the Shaker channel, although hERG has less gating charge in its S4 than in Shaker. Furthermore, channel domain other than S4 contributes to gating charge involved in hERG's inactivation process.

Amino Acid Substitution↗