Biomedical subjects

Wenhua Zhang

Publications and source records attributed to Wenhua Zhang.

At least 19 recordsLinked to original sources

PubMed2004

Clinically approved heterocyclics act on a mitochondrial target and reduce stroke-induced pathology.

Substantial evidence indicates that mitochondria are a major checkpoint in several pathways leading to neuronal cell death, but discerning critical propagation stages from downstream consequences has been difficult. The mitochondrial permeability transition (mPT) may be critical in stroke-related injury. To address this hypothesis, identify potential therapeutics, and screen for new uses for established drugs with known toxicity, 1,040 FDA-approved drugs and other bioactive compounds were tested as potential mPT inhibitors. We report the identification of 28 structurally related drugs, including tricyclic antidepressants and antipsychotics, capable of delaying the mPT. Clinically achievable doses of one drug in this general structural class that inhibits mPT, promethazine, were protective in both in vitro and mouse models of stroke. Specifically, promethazine protected primary neuronal cultures subjected to oxygen-glucose deprivation and reduced infarct size and neurological impairment in mice subjected to middle cerebral artery occlusion/reperfusion. These results, in conjunction with new insights provided to older studies, (a) suggest a class of safe, tolerable drugs for stroke and neurodegeneration; (b) provide new tools for understanding mitochondrial roles in neuronal cell death; (c) demonstrate the clinical/experimental value of screening collections of bioactive compounds enriched in clinically available agents; and (d) provide discovery-based evidence that mPT is an essential, causative event in stroke-related injury.

Animals↗

PubMed2004

Phospholipase D alpha 1-derived phosphatidic acid interacts with ABI1 phosphatase 2C and regulates abscisic acid signaling.

Phospholipase D (PLD) and protein phosphatase 2C (PP2C) both play a role in mediating plant responses to abscisic acid (ABA). In this article, we show that PLD alpha 1 and its product, phosphatidic acid (PA), regulate a PP2C, ABI1, which is a negative regulator of ABA responses in Arabidopsis. Leaves from a T-DNA insertional mutant of PLD alpha 1 and PLD alpha 1-antisense plants lose more water than do wild-type plants. The stomatal closure of PLD alpha 1-null leaves is insensitive to ABA but is promoted by PA. ABA treatment promotes an increase in PA from phosphatidylcholine in wild type but not in PLD alpha 1-null cells. PLD alpha 1-derived PA binds to ABI1; the PA-ABI1 binding is demonstrated by coprecipitating PA with ABI1 from plant cells, measuring binding of PA from vesicles to ABI1, and assaying ABI1 bound to PA immobilized on a filter. Deletion and site-specific mutational analyses show that arginine 73 in ABI1 is essential for PA-ABI1 binding. PA binding decreases the phosphatase activity of ABI1. The lack of ABA-induced production of PA in PLD alpha 1-null cells results in a decrease in the association of ABI1 with the plasma membrane in response to ABA. These results indicate that PA produced by PLD alpha 1 inhibits the function of the negative regulator ABI1, thus promoting ABA signaling. The identification of ABI1 as a direct target of the lipid messenger PA provides a functional link between the two families of important signaling enzymes, PLD and PP2C.

Abscisic Acid↗

PubMed2004

The plasma membrane-bound phospholipase Ddelta enhances freezing tolerance in Arabidopsis thaliana.

Freezing injury is a major environmental limitation on the productivity and geographical distribution of plants. Here we show that freezing tolerance can be manipulated in Arabidopsis thaliana by genetic alteration of the gene encoding phospholipase Ddelta (PLDdelta), which is involved in membrane lipid hydrolysis and cell signaling. Genetic knockout of the plasma membrane-associated PLDdelta rendered A. thaliana plants more sensitive to freezing, whereas overexpression of PLDdelta increased freezing tolerance. Lipid profiling revealed that PLDdelta contributed approximately 20% of the phosphatidic acid produced in wild-type plants during freezing, and overexpression of PLDdelta increased the production of phosphatidic acid species. The PLDdelta alterations did not affect the expression of the cold-regulated genes COR47 or COR78 or alter cold-induced increases in proline or soluble sugars, suggesting that the PLD pathway is a unique determinant of the response to freezing and may present opportunities for improving plant freezing tolerance.

Arabidopsis↗

PubMed2003

The oleate-stimulated phospholipase D, PLDdelta, and phosphatidic acid decrease H2O2-induced cell death in Arabidopsis.

Hydrolysis of common membrane phospholipids occurs in response to various environmental stresses, but the control and cellular function of this hydrolysis are not fully understood. Hydrogen peroxide (H2O2) is a pivotal signaling molecule involved in various stress responses. Here, we show that the plasma membrane-bound phospholipase D, PLDdelta, is activated in response to H2O2 and that the resulting phosphatidic acid (PA) functions to decrease H2O2-promoted programmed cell death. The Arabidopsis genome has 12 PLD genes, and knockout of PLDdelta abolishes specifically the oleate-stimulated PLD activity. H2O2 treatment of Arabidopsis cells activates PLD enzyme activity, and ablation of PLDdelta abolishes that activation. PLDdelta-null cells display increased sensitivity to H2O2-induced cell death. The addition of PA to PLDdelta-null cells mitigates the H2O2 effect, whereas suppression of the H2O2-induced PA formation in wild-type cells increases the effect. PLDdelta-ablated plants exhibit increased susceptibility to stress. These results demonstrate that activation of oleate-stimulated PLDdelta constitutes an important step in the plant response to H2O2 and increasing plant stress tolerance.

Apoptosis↗

PubMed2003

Minocycline inhibits caspase-independent and -dependent mitochondrial cell death pathways in models of Huntington's disease.

Minocycline is broadly protective in neurologic disease models featuring cell death and is being evaluated in clinical trials. We previously demonstrated that minocycline-mediated protection against caspase-dependent cell death related to its ability to prevent mitochondrial cytochrome c release. These results do not explain whether or how minocycline protects against caspase-independent cell death. Furthermore, there is no information on whether Smac/Diablo or apoptosis-inducing factor might play a role in chronic neurodegeneration. In a striatal cell model of Huntington's disease and in R6/2 mice, we demonstrate the association of cell death/disease progression with the recruitment of mitochondrial caspase-independent (apoptosis-inducing factor) and caspase-dependent (Smac/Diablo and cytochrome c) triggers. We show that minocycline is a drug that directly inhibits both caspase-independent and -dependent mitochondrial cell death pathways. Furthermore, this report demonstrates recruitment of Smac/Diablo and apoptosis-inducing factor in chronic neurodegeneration. Our results further delineate the mechanism by which minocycline mediates its remarkably broad neuroprotective effects.

Animals↗

PubMed2003

A new thioether functionalized organic-inorganic mesoporous composite as a highly selective and capacious Hg2+ adsorbent.

A new thioether functionalized organic-inorganic ordered mesoporous composite as a highly selective and capacious Hg2+ adsorbent was synthesized by one-step co-condensation of (1,4)-bis(triethoxysilyl)propane tetrasufide (BTESPTS, (CH3CH2O)3Si(CH2)3S-S-S-S(CH2)3Si(OCH2CH3)3) and tetraethoxysilane (TEOS), with tri-block copolymer poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) EO20PO70EO20 as template.

Journal Article↗

PubMed2003

Additive neuroprotective effects of minocycline with creatine in a mouse model of ALS.

The known neuroprotective effects of minocycline and creatine in animal models of amyotrophic lateral sclerosis (ALS) led us to examine whether the combination of these agents would result in increased neuroprotection. As previously reported, we confirmed in ALS mice that either minocycline or creatine treatment results in improvement in motor performance and extended survival. We report that combination of minocycline and creatine resulted in additive neuroprotection, suggesting this to be a novel potential strategy for the treatment of ALS. To our knowledge, this is the first report demonstrating additive neuroprotection of a combinatorial approach in a mouse model of ALS. Adding relevancy to our findings, minocycline and creatine, are relatively safe, cross the blood-brain barrier, and are currently available for human evaluation.

Amyotrophic Lateral Sclerosis↗

PubMed2003

Exogenous silicon (Si) increases antioxidant enzyme activity and reduces lipid peroxidation in roots of salt-stressed barley (Hordeum vulgare L.).

Two contrasting barley (Hordeum vulgare L.) cultivars, i.e. Kepin No.7 (salt sensitive) and Jian 4 (salt tolerant), were grown hydroponically to study the effect of exogenous silicon (Si) on time dependent changes of the activities of major antioxidant enzymes and of lipid peroxidation in roots under salt stress. Enzymes included: superoxide dismutase (SOD), peroxidase (POD), catalase (CAT) and glutathione reductase (GR). Three treatments with three replicates were investigated consisting of a control (basal nutrients with neither NaCl nor Si added), 120 mmol/L-1 NaCl, and 120 mmol/L-1 NaCl +1.0 mmol/L-1 Si. Plant roots were harvested 2, 4 and 6 days after treatment and assayed for activities of the antioxidant enzymes and the concentrations of reduced glutathione (GSH) and malondialdehyde (MDA), and electrolytic leakage percentage (ELP). The activities of SOD, POD and CAT in roots of salt-stressed plants were significantly stimulated at Day 2 compared to control plants, but considerably decreased at Day 4 and onward. GR activity in roots of salt-stressed plants remained unchanged at Day 2, but significantly decreased at Day 4 and onward. However, exogenous Si significantly enhanced these enzyme activities in roots of salt-stressed plants compared to Si-deprived salt treatments. This Si effect was time-dependent and became stronger as the experiments continued. The tendency of change in the activities of antioxidant enzymes and the concentration of GSH coincided with the concentration of MDA, the end product of lipid peroxidation, and the ELP. Higher activities of antioxidant enzymes, and higher concentration of GSH, but lower concentration of MDA and lower ELP were noted in cultivar Jian 4 compared to Kepin No. 7, implying genotypic differences with Jian 4 being less susceptible to stress-dependent membrane lipid peroxidation. The effects of Si-enhanced salt tolerance are discussed with respect to cell membrane integrity, stability and function in barley.

Antioxidants↗

PubMed2003

Rat corneal allograft survival prolonged by the superantigen staphylococcal enterotoxin B.

PURPOSE: The purpose of this study was to determine the optimal conditions for prolonging corneal allograft survival by inducing anergy with the superantigen staphylococcal enterotoxin B (SEB). METHODS: A rat model of penetrating keratoplasty, whereby Fisher344 donor corneas are implanted into Lewis recipients, was used to evaluate the effects of SEB on inhibiting immune-mediated allograft rejection. To induce anergy, SEB was injected into the peribulbar space of Lewis rats. Furthermore, histopathology and immunofluorescent staining were used to examine the levels of infiltrating CD4(+) and CD8(+) T lymphocytes and NK1.1(+) lymphocytes. RESULTS: By administering SEB, at doses of 90 or 120 micro g/kg 7 days before and after keratoplasty, we suppressed the episode of corneal graft rejection for a median of 12 and 30 days, respectively. In contrast, rejection was observed when 30 or 60 micro g/kg of SEB was administered. After SEB injections, lymphocyte infiltration into the corneal grafts was reduced, and the expression of NK1.1(+) lymphocytes was enhanced, suggesting that anergy may be occurring. Also, there were no differences in the number of infiltrating CD4(+) and CD8(+) T lymphocytes cells between the control group and groups injected with 30 and 120 micro g/kg SEB on postoperative days 10 and 30. CONCLUSIONS: Inducing anergy with the superantigen SEB prolonged corneal graft survival in a rat model of penetrating keratoplasty. Therefore, these results support the possibility of prolonging corneal allograft survival in a clinical setting by preventing immune-mediated rejection through the administration of the superantigen SEB.

Animals↗

PubMed2003

[Salt tolerance of wild soybeans in Jiangsu and its relation with ionic distribution and selective transportation].

The salt tolerance of 3 wild soybean (Glycine soja) populations was compared with their relative germination and seedling emergence. The results showed that the salt tolerance of Jiangsu wild soybean (JWS) was the strongest. Under NaCl stress, the dry matter accumulation in wild soybean seedlings decreased, root/shoot ratio increased, and these effects were greater in N23232 (salt-sensitive) than in JWS (salt-tolerant). Determinations on the ion contents in different organs indicated that the Na+ content was higher in stem than in other organs, and the accumulation of Na+ and Cl- in roots was significantly more in JWS than in N23232. The contents of these ions in JWS leaves were much less than those in N23232 leaves. There was no significant difference between selective absorptions of K+ and Na+ (ASK, Na) by the two populations, but the selective transportation of K+ and Na+ (TSK, Na) in stem and leaf was much higher in JWS than in N23232, resulted in the higher K+/Na+ ratio in JWS shoots. It is suggested that the main reason for the salt tolerance in salt-tolerant wild soybean was the accumulation of Na+ and Cl- in roots and stems and the higher selective transportation of K+ from root to shoot.

Germination↗

PubMed2002

[Clinical analysis of 74 cases with ovarian thecoma].

OBJECTIVE: To study the clinical pathologic characteristics, treatment and prognostic factors of ovarian thecoma. METHODS: From 1958 approximately 1998, a total of 74 patients with benign and malignant thecoma were retrospectively analyzed. RESULTS: The reviewed diagnosis were 8 patients with malignant thecoma, 66 patients were benign thecoma. Nine of 66 patients with benign thecoma appeared cell proliferative activity. The mean age was 52 years. The most frequent symptoms were abdominal-pelvic masses (56.8%), metromenorrhagia and abnormal vaginal bleeding, other symptoms were abdominal pain, infertility followed. Twenty-two of 66 patients had ascites, only 1 patient with ascites and hydrothorax simultaneously. Thirty-nine patients with diseases which associate with excessive estrogenic stimulation, including 1 endometrial adenocarcinoma and 1 endometrial dysplasia and other diseases such as: myoma; endometrial hyperplasia and polyp. Fifteen patients with benign thecoma were evaluated blood serum CA(125), the CA(125) were elevated in 9 of 15 patients. In 2 of 9 patients with cell proliferative activity, the tumors invaded adjacent tissues or relapsed, after received operation and pelvic radiotherapy, they are alive 11 years and 27 years respectively. Among 8 patients with malignant thecoma, 4 patients without postoperation therapy or with non-standard chemotherapy died in 2 years postoperation, the other 4 patients received operation, postoperational radiotherapy or (and) chemotherapy, 1 of 4 patients died of irradiation intestinal fistule 4 years later; two patients are alive without disease more than 10 years, another one for 2 years. CONCLUSIONS: Theca cell tumor of ovary have good prognosis, but we should pay attention to thecomas with proliferative activity. The prognosis of malignant thecomas is poor, postoperative systemic chemotherapy or radiotherapy to the patients with malignant thecomas can improve their survival.

Adolescent↗

PubMed2002

[The variance of pathogenic organisms of purulent ulcerative keratitis].

OBJECTIVE: To identify the variance of pathogens of purulent keratitis and their resistance patterns to antibiotics. METHODS: From January 1995 to October 2000, all patients with suspected infectious corneal ulcer were examined by bacterial, fungal and Acanthameoba culture. The results of microorganism-culture were compared with those in literature. RESULTS: Of the specimens in 1 430 cases, there were 790 cases (55.2%) with positive culture including bacterial isolates in 258 cases (18.0%), fungal isolates in 498 cases (34.8%) and parasites in 34 cases (2.4%). The Staphylococcus aureous and Pseudomonas aeruginosa that had markedly declined since 1980s represented 6.2% and 21.7% of bacterial isolates respectively. However, the opportunity organism such as Staphylococcus epidermidis represented 27.5%, a tendency of gradual increase. The most common fungal pathogen was fusarium spp that represented 64.5% of all positive fungal cultures, and Aspergillus spp (13.6%) occupied the second place. The resistance of the ocular bacteria to fluoroquinolones gradually increased. Although the Pseudomonas aeruginosa was resistant to gentamycin in 36.2%, it was almost no resistance to tobramycin (3.4%). The fusarium spp was shown to be resistant to a number of the anti-fungal agents, but it is sensitive to natamycin. CONCLUSION: The survey of pathogens in purulent ulcerative keratitis and their resistance patterns to antibiotics helps in clinical treatment.

Acanthamoeba↗

PubMed2002

[Distribution and shifting trends of the pathogens for bacterial keratitis].

OBJECTIVE: To study the distribution and shifting trends of corneal bacterial isolates from bacterial keratitis retrospectively. METHODS: The data of bacterial cultures of 2 220 corneal isolates from January, 1989 to December, 1998 were reviewed. RESULTS: During this 10-year period, 2 220 consecutive corneal cultures were obtained, and a positive-culture was recovered in 490 isolates, the positive rate being 22.1%. In the 490 positive-cultures, Gram-positive cocci and Gram-negative bacilli represented 51.0% and 39.4% respectively. Gram-positive bacilli was 9.2%. Pseudomonas aeruginosa was isolated the most commonly in the corneal isolates (32.2%), followed by coagulase-negative staphylococcus (18.6%). Streptococcus pneumoniae represented 12.0%. During this period, we documented a gradual increase in the number of Gram-positive cocci coupled with a decrease of the number of Gram-negative bacilli. CONCLUSION: Pseudomonas aeruginosa and coagulase-negative staphylococcus are the most common pathogens in bacterial keratitis in the north part of China. At present, the increased recovery of Gram-positive cocci and decreased of Gram-negative bacilli from keratitis isolates present an important challenge to the ophthalmology.

China↗

PubMed2002

Transplantation of corneal stem cells cultured on amniotic membrane for corneal burn: experimental and clinical study.

OBJECTIVE: To investigate the proliferation and differentiation of cultured corneal stem cells and determine the effect of corneal stem cells cultured on amniotic membranes on the limbal area for treating corneal burns. METHODS: The proliferation and differentiation of corneal stem cells in vitro had been examined using colony-forming efficiency and immunohistochemistry. The stem cells had been cultured on amniotic membranes and transplanted to the limbal area for treating corneal burns. RESULTS: Corneal stem cells had a high proliferation capacity in primary and first passage, cytokeratin 3 was not expressed in primary culture but partly in first passage. The stem cells could proliferate to form cell layer on an amniotic membrane. When transplanted, stem cells could survive on limbus. After transplantation, ocular inflammation resolved, the cornea re-epithelialized, the stromal opacity reduced, the superficial neovascularity was lessened and the conjunctival fornix re-established. CONCLUSIONS: Ocular surface conditions could be improved by allograft of corneal stem cells cultured on amniotic membranes.

Alkalies↗

PubMed2002

Etiological analysis on bacterial ocular disease in northern China (1989-1998).

OBJECTIVE: To review the distribution and trends of bacterial culture specimens in Beijing Institute of Ophthalmology. METHODS: A retrospective analysis of the bacterial culture-positive rate, the distribution of gram' s stain, and the distribution and change of isolates was performed on 4705 specimens during a 10-year period (1989- 1998). RESULTS: Positive cultures numbered 1339 of the 4705 specimens, with a positive rate of 28.6%. Gram-positive cocci constituted 55.6% of the total isolates, followed by gram-positive bacilli 13.1% . Gram-negative cocci accounted for 2.8%, and gram-negative bacilli 28.5% . In the positive bacteria cultures, coagulase-negative Staphylococcus (mainly Staphylococcous epidermidis) was the most common isolate (25.3%), and followed by Pseudomonas 18.8%, Micrococcus 11.7%, Cotynbaccterium 10.1%, and Staphylococcus aureus 8.2% . During the 10-year period, the overall frequency of gram-positive cocci appeared to increase with time while the frequency of gram-negative bacilli decreased. CONCLUSIONS: Gram-positive cocci and gram-negative bacilli are still the predominant pathogens of ocular infection in northern China. The frequency of the former increases annually whereas that of the latter decreases. It is important to comprehend the distribution and trends of ocular pathogenic bacteria for the diagnosis, prevention and treatment of bacterial infectious ocular disease.

Bacteria↗

PubMed2002

[Experimental study on the treatment of corneal melting after alkali burn with GM 6001].

OBJECTIVE: To eva1uate the effect of synthetic inhibitors of matrix metalloproteinases (GM 6001) on the prevention of melting of rabbit corneas after alkali burn. METHODS: Severe and moderate rabbit alkali burns were made by different concentrations of NaOH. Corneas with severe or moderate alkali injuries were topically treated with 400 mg/L or 200 mg/L GM 6001 for 30 days. Vehicle was used as control. All corneas were evaluated for melting, opacity and other pathological changes. RESULTS: After severe alkali burns, all of the 8 corneas of the control group melted in 13 +/- 5 days, and 2 corneas perforated. Only did 2 corneas melt in 19 +/- 4 days after burn and not perforate in 400 mg/L GM 6001 group. The rates of corneal melting and perforation in 400 mg/L GM 6001 group were lower than that of the control (P < 0.05), and the initial time of melting was later than that of the control (P < 0.0l). After moderate alkali burn, all of the 6 corneas of control melted in 14 +/- 6 days, and 1 cornea perforated. Only did 2 of 200 mg/L GM 6001 treated corneas melt in 19 +/- 4 days without perforation after burn. The rate of corneal melting and the degree of corneal opacity were lower in 200 mg/L GM 6001 treated than that of the control, the difference being significant (P < 0.0l). Histologic section of GM 6001 treated corneas revealed much less collagen fiber destruction and inflammatory cell infiltration than that of the control. CONCLUSION: GM 6001 not only can prevent and delay the corneal melting after alkali burn, but also can reduce the destruction of corneal collagen fibers and infiltration of inflammatory cells in the corneal tissue.

Alkalies↗

PubMed2002

Etiological analysis on the ocular fungal infection.

OBJECTIVE: To review the distribution and shifting trends of fungal culture specimens in Beijing Institute of Ophthalmology. METHODS: Retrospective analyses of the fungal culture positive rate, the distribution and change of isolates were performed on 2 609 specimens during a 12-year period (1989 - 2000). RESULTS: The number of positive cultures was 775 (707 from the cornea, 91.23%; 22 from the conjunctiva, 2.84%; 15 from anterior chamber, 1.94%; 9 from the vitreous body, 1.16%; 3 from lacrimal sac, 0.39% and 19 from other parts of eye, 2.45%). The average culture-positive rate was 29.70%. The average ratio of the positive cultures between the first half (from January to June) and the second half (from July to December) of the years was 1:2.1. The main genus cultured was Fusarium (58.71%), next was Aspergillus (16.8%). The percentage of Fusarium was increased (53.63% from 1989 through 1994 to 60.23% from 1995 through 2000), and the percentage Aspergillus was decreased (22.35% from 1989 through 1994 to 15.10% from 1995 through 2000). CONCLUSIONS: The Fusaruim is the predominant pathogens of ocular fungal infection in the northern part of China, its frequency was increased during this 12-year period, and meanwhile the frequency of the Aspergillus was decreased. It is very important to comprehend the distribution and shifting trends of pathogenic fungi continuously for diagnosis, prevention and treatment of fungal infectious ocular disease.

Aspergillus↗

PubMed2002

Retrospective analysis of 67 consecutive cases of pure ovarian immature teratoma.

OBJECTIVE: To investigate the development regularity, treatment methods and prognosis of ovary immature teratoma (POIT). METHODS: Sixty-seven patients with POIT, admitted from 1958 to 1998, were retrospectively analyzed. There were 31 patients with stage I, 4 with stage II, 2 with stage III and 1 with stage IV lesions. Twenty-seven patients had recurrences and 2 had distant metastases. Unilateral adnexectomy was performed for stage I lesions. From the 1980s, this was followed by four-cycles of combination chemotherapy (VAC, PVB or BEP x 3 cycles) as post-operative adjuvant therapy. Combined chemotherapy and multiple operations were performed for advanced and recurrent lesions. RESULTS: The overall survival rate was 75% (50/67). However, there was a remarkable difference in the results from the various periods. From 1958 to 1983, the 5-year survival rate was 40% (6/15), and it was raised to 79% (26/33) from 1984 to 1993. In the period 1994 to 1998, 95% (18/19)of patients were rescued. Thirty-five patients who had early lesions (stage I and II) had a 5-year survival rate of 91.4% (32/35). Thirty-two patients with recurrent or advanced lesions had a 5-years survival rate of 56% (18/32). There were 8 patients with grade III tumors and their 5-year survival rate was only 25% (2/8). The chief prognostic factors for this disease are clinical stage, pathological grade and adequate treatment. CONCLUSION: POIT is a potentially curable disease in today's practice. It is characterized by the fact that recurrent tumors may be converted back to mature ones as time goes on. With chemotherapy, these is a good opportunity to rescue those patients with recurrent tumors. At present, treatment of POIT gives the most satisfactory results among all malignant ovarian germ cell tumor types. Tests of serum specific tumor markers (CA19-9, AFP, CA125, CEA) performed preoperatively or before chemotherapy and during follow-up have been found helpful in the evaluation of prognosis.

Adolescent↗