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Biomedical subjects

Fang Fang

Publications and source records attributed to Fang Fang.

At least 37 records · Page 2Linked to original sources

Essential sequence of influenza neuraminidase DNA to provide protection against lethal viral infection.

Neuraminidase (NA) is one of the surface glycoproteins of influenza virus. The immune response induced by NA DNA in the mouse model has been proved, in our previous study, to be able to provide an adequate protection against the challenge with a homologous virus and a crossprotection against the challenge with a heterologous virus of the same subtype. In this paper, a series of NA plasmid truncates, with the nucleotides at the 5'- or 3'-terminal of A/PR/8/34 (H1N1) NA deleted serially, were constructed by PCR. BALB/c mice were immunized with the plasmid truncates and challenged with homologous virus at a lethal dosage. The essential sequence of NA DNA to provide protection against the influenza virus was explored by observing the survival rates, serum anti-NA antibody titers, and lung virus titers of the mice. The result showed that, along with the increasing number of nucleotides deleted serially at the 5'- or 3'-terminal of NA DNA, the antibody titer induced by NA DNA decreased. NA DNA lost its protection against the influenza virus when 60 nucleotides (or 20 amino acids) at the 5'-terminal or 66 nucleotides (or 22 amino acids) at the 3'-terminal were deleted. The nt58-1299 of NA DNA may play an important role in protection against influenza virus.

Amino Acid Sequence↗

Protective effects of compound FLZ on beta-amyloid peptide-(25-35)-induced mouse hippocampal injury and learning and memory impairment.

AIM: To study the protective effects of compound FLZ, a novel synthetic analogue of natural squamosamide, on learning and memory impairment and lesions of the hippocampus caused by icv injection of beta-amyloid(25-35)(Abeta(25-35)) in mice. METHODS: Mice were icv injected with the Abeta(25-35) (15 nmol/mouse), and then treated with oral administration of 75 mg/kg or 150 mg/kg of FLZ once daily for 16 consecutive days. The impairment of learning and memory in mice were tested using step-down test and Morris water maze test. The content of malondialdehyde (MDA) and the expressions of acetylcholinesterase (AChE), Bax, and Bcl-2 in the CA1 region of the mouse hippocampus were measured by biochemical and immunohistochemical analysis, respectively. The pathological damages of hippocampus were observed using a microscope. RESULTS: FLZ (75 mg/kg, 150 mg/kg) significantly attenuated Abeta(25-35)-induced impairment of learning and memory in the step-down test and Morris water maze test. FLZ also reduced pathological damages to the hippocampus induced by Abeta(25-35). Furthermore, FLZ prevented the increase of AChE and Bax, and the decrease of Bcl-2 immunoreactive cells in the CA1 region of the hippocampus, and reduced the increase of MDA content in the hippocampus in mice injected with Abeta(25-35). CONCLUSION: FLZ has protective action against the impairment of learning and memory and pathological damage to the hippocampus induced by icv injection of Abeta(25-35) in mice.

Acetylcholinesterase↗

Sialidase fusion protein as a novel broad-spectrum inhibitor of influenza virus infection.

Influenza is a highly infectious disease characterized by recurrent annual epidemics and unpredictable major worldwide pandemics. Rapid spread of the highly pathogenic avian H5N1 strain and escalating human infections by the virus have set off the alarm for a global pandemic. To provide an urgently needed alternative treatment modality for influenza, we have generated a recombinant fusion protein composed of a sialidase catalytic domain derived from Actinomyces viscosus fused with a cell surface-anchoring sequence. The sialidase fusion protein is to be applied topically as an inhalant to remove the influenza viral receptors, sialic acids, from the airway epithelium. We demonstrate that a sialidase fusion construct, DAS181, effectively cleaves sialic acid receptors used by both human and avian influenza viruses. The treatment provides long-lasting effect and is nontoxic to the cells. DAS181 demonstrated potent antiviral and cell protective efficacies against a panel of laboratory strains and clinical isolates of IFV A and IFV B, with virus replication inhibition 50% effective concentrations in the range of 0.04 to 0.9 nM. Mouse and ferret studies confirmed significant in vivo efficacy of the sialidase fusion in both prophylactic and treatment modes.

Amphiregulin↗

Constitutive activation of two-component response regulators: characterization of VirG activation in Agrobacterium tumefaciens.

Response regulators are the ultimate modulators in two-component signal transduction pathways. The N-terminal receiver domains generally accept phosphates from cognate histidine kinases to control output. VirG for example, the response regulator of the VirA/VirG two-component system in Agrobacterium tumefaciens, mediates the expression of virulence genes in response to plant host signals. Response regulators have a highly conserved structure and share a similar conformational activation upon phosphorylation, yet the sequence and structural features that determine or perturb the cooperative activation events are ill defined. Here we use VirG and the unique features of the Agrobacterium system to extend our understanding of the response regulator activation. Two previously isolated constitutive VirG mutants, VirGN54D and VirGI77V/D52E, provide the foundation for our studies. In vivo phosphorylation patterns establish that VirGN54D is able to accumulate phosphates from small-molecule phosphate donors, such as acetyl phosphate, while the VirGI77V/D52E allele carries conformational changes mimicking the active conformation. Further structural alterations on these two alleles begin to reveal the changes necessary for response regulator activation.

Agrobacterium tumefaciens↗

[Correlation research between cancer stem cells and the pathological grades of neuroepithelial tumors].

OBJECTIVE: To explore the methods of isolation, culture and identification of brain tumor stem cells (BTSCs) in neuroepithelial tumor tissues in vitro, and to study the correlation between BTSCs and the patholorical grades of neuroepithelial tumors. METHODS: Tumor cells from patients undergoing neuroepithelial tumors excision were acutely dissociated, triturated into single cells, and then seeded into serum-free medium. After the primary brain tumor spheres (BTSs) were generated, they were triturated again and passaged in fresh medium. The expression of Nestin and CD133 of BTSs was detected by immunocytochemistry staining, and the expression of CD133 of tumor specimen sections was detected by immunohistochemistry staining . The expression of CD133 of 46 brain tumors and 5 normal brain tissues were analysed by SABC immunohistochemical staining, and the correlation between the expression and pathological grade of the tumors was analysed. RESULTS: BTSCs from neuroepithelial tumors could be isolated and cultured, and could be generated and passaged in vitro. The expression of Nestin and CD133 could be detected in BTSCs. CD133 could be detected in neuroepithelial tumor tissues, but not in normal brain tissues. There was significant difference between the expression of CD133 and the different grades of tumors (P < 0.01), and there was a positive correlation between the expression of CD133 and the histologic grading of tumors (P < 0.01). CONCLUSION: A small proportion of stem cells have the ability to self-renew in human neuroepithelial tumors, and there is a positive correlation between the expression of CD133 and histologic grading of tumors.

AC133 Antigen↗

[Start-up experiment on nitrification of mid-low ammonia concentration wastewater in SBR biofilm reactor].

The start-up experiment on nitrification of mid-low NH4+ -N concentration wastewater was carried out in four SBR biofilm reactors for the establishment of completely autotrophic nitrogen removal process by the control of DO and HRT and different medias. The results show that on the conditions of temperature 30 degrees C +/-2 degrees C, ammonia concentration 60-120 mg/L, DO 0.8 - 1.0 mg/L and hydraulic retention time 24 h, the inoculating general active aerobic sludge and anaerobic sludge was nitrified stably after 130 days, and the YJZH media was more suitable for microorganism coherence.

Ammonia↗

[Cerebral venous sinus thrombosis].

Cerebral venous sinus thrombosis (CVST) rarely occurs in children but has a mortality rate as high as 20%-78%. Because the clinical manifestation of this disease has no specificity it is easy to be misdiagnosed. This paper reported a case of CVST and reviewed the relevant literatures regarding to the pathogenesis, clinical and pathological features, diagnosis and treatment. The patient (male, 8 months old) was referred to the Beijing Children's Hospital with paroxysm headache and after vomiting for 50 days and having double visions for 2 days. He was definitely diagnosed with CVST by magnetic resonance imaging (MRI) and magnetic resonance venography (MRV). His neurological symptoms were improved after receiving intravenous urokinase and hormonal therapy for three weeks followed by oral anticoagulation. It is concluded that headache and papilledema are the most frequent symptoms in CVST and that MRI and MRV may be primal methods for the diagnosis of CVST.

Child↗

[Inhibitory action of propyl gallate on the activation of SAPK/JNK and p38MAPK induced by cerebral ischemia-reperfusion in rats].

AIM: To explore the protective effect of propyl gallate against neuronal injury in the boundary zone of the infarction area in the rat cerebral ischemia-reperfusion model and its possible mechanism. METHODS: Transient focal ischemia induced by middle cerebral artery occlusion in the rats was established by ligation of the left internal carotid artery for 2 h. Rats were treated by propyl gallate with different doses (23.5, 47 and 94 micromol x kg(-1)) for three days before operation. Coronal brain sections were collected after 1 , 2, 4, 6, 12 and 24 h of reperfusion, neuronal injury in the boundary zone of the infarction area was evaluated by TUNEL and Nissl staining. The expression of activated Caspase-3, total SAPK/JNK, p38MAPK and their phosphorylation (Thr183/Tyr185, Thr180/Tyr182) was investigated by immunohistochemistry and Western blotting with corresponding antibodies. RESULTS: Although SAPK/JNK immunoreactivity did not increase at each time point in the boundary zone of the infarction area after reperfusion, p-SAPK/JNK immunoreactivity increased significantly at 1 h and then decreased gradually, and p38MAPK immunoreactivity was enhanced at each time point, peaked at 6 h. Expression of p-p38MAPK peaked at 6 h. Activated Caspase-3 immunoreactivity appeared at 6 h in the boundary zone of the infarction area and peaked at 12 h. TUNEL positive neurons were observed at 12 h and became more abundant at 24 h. The number of Nissl positive neurons decreased gradually and apoptosis ratio of neurons peaked at 24 h. Propyl gallate reduced the immunoreactivity of SAPK/JNK, p-SAPK/JNK, p38MAPK and p-p38MAPK markedly at 1 and 6 h. Propyl gallate with doses of 47 and 94 micromol x kg(-1) were more effective. CONCLUSION: Inhibition on the activation of SAPK/JNK and p38MAPK is the possible protective mechanism of propyl gallate against neuronal injury induced by cerebral ischemia-reperfusion.

Animals↗

Cyclooxygenase-2 inhibitor, nimesulide, improves radiation treatment against non-small cell lung cancer both in vitro and in vivo.

Lung cancer is the leading cause of cancer-related deaths in the United States. Despite improvements in radiation, surgery and chemotherapy the 5 year survival statistics of non-small cell lung cancer (NSCLC) have improved little over the past two decades. It has been proposed that NF-kappaB is a participant in the cytoprotection against several redox-mediated therapeutic agents including ionizing radiation. Cyclooxygenase-2 (COX-2) inhibition has become an attractive target for enhancing the efficacy of radiation and chemotherapy. Numerous mechanistic pathways have been proposed as the means through which COX-2 inhibition enhances the efficacy of radiation. We hypothesize that the COX-2 inhibitor, nimesulide, will improve the efficacy of radiation therapy (RT), at least in part, via the suppression of NF-kappaB mediated cytoprotective pathways. In this study we used the COX-2 inhibitor nimesulide to improve the efficacy of RT when measured by tumor regrowth assays in vivo and clonegenic survival in vitro. For the in vivo assay, A549 tumor cells representing NSCLC were subcutaneously injected into the right flanks of female athymic nude mice (n=10/group). Mice were given nimesulide via drinking water at a concentration of 5 microg/g body weight (b.w.) and the water was replenished daily. Tumors were treated with 30 Gy fractionated radiation and measured bi-weekly. For our in vitro study, clonogenic survival assays were evaluated to determine the effect of nimesulide, radiation, and the combination. The NF-kappaB mediated mechanism of nimesulide was measured by Western blot analysis of NF-kappaB target genes, MnSOD and survivin. In vivo, mice that received combined treatments of 5 microg/g b.w. nimesulide and 30 Gy radiation (3 Gy/fraction, 10 daily fractions) had significant reduction in tumor size in comparison to the 30 Gy radiation control group (p<0.05). In vitro, nimesulide alone produced a significant decrease in clonogenic survival at doses from 0-300 microM. Nimesulide demonstrated an additive effect in combination with radiation. Nimesulide alone reduced MnSOD and survivin protein levels in a dose-dependent manner. 6 Gy radiation caused an initial elevation of MnSOD protein levels which was inhibited by prior treatment of nimesulide suggesting an inhibition of radiation induced NF-kappaB target genes. These results support the hypothesis that COX-2 inhibitors such as nimesulide can increase the efficacy of radiation therapy. In vitro, our results suggest that the radiosensitization of A549 tumor cells by nimesulide is mediated by the suppression of NF-kappaB-mediated, radiation-induced cytoprotective genes.

Animals↗

Mitomycin C "straight scleral tunnel incision"--trabeculectomy with a releasable suture.

OBJECTIVE: To evaluate the efficacy of "straight scleral tunnel incision" -trabeculectomy with a releasable suture supplemented with mitomycin C (MMC) on reducing intraocular pressure (IOP), complications, and corneal astigmatism in patients with primary angle-closure glaucoma (PACG). METHODS: Totally 217 acute or chronic PACG patients with occludable angle above 180 degrees and IOP above 21 mm Hg were divided into 3 groups. Patients in group A (98 cases, 128 eyes), B (71 cases, 95 eyes), and C (48 cases, 60 eyes) were treated with "straight scleral tunnel incision"-trabeculectomy with a releasable suture supplemented with MMC, releasable suture trabeculectomy with MMC, and trabeculectomy with MMC, respectively. IOP, complications, and surgically induced astigmatism (SIA) were evaluated preoperatively and up to 12 months postoperatively. RESULTS: IOP of 2 weeks after treatment was significantly lower than preoperative IOP in all the 3 groups (all P <0. 001). Success rates (IOP < or = 20 mm Hg) in group A, B, and C were 87.91%, 89.23%, and 83.72% respectively at 12 months after treatment (P = 0.256). The incidence of shallow anterior chamber and hypotony had no significant difference between group A and B, but both of them were lower than that in group C (P < 0.05). There were no significant differences in preoperative corneal astigmatism among the 3 groups. The corneal astigmatism after 2 weeks in group A (1.71 +/- 1.47D) was higher than that before operation (1.28 +/- 1.05D, P = 0.126). With 12 months gone, the astigmatism almost returned to preoperative levels. The corneal astigmatisms after 2 weeks in group B and C (1.99 +/- 1.20D and 2. 22 +/- 1.39D) were significantly higher than those before operation (1.20 +/- 0.85D and 1.18 +/- 0.93D, P = 0.002, P = 0.001), respectively. With 12 months gone, the mean astigmatisms in group B and C (1.87 +/- 0.91D and 1.90 +/- 1.16D) were still significantly higher than those before operation (P = 0.001, P = 0.003). The highest astigmatic polar values in group A, B, and C (1.00D, 1. 89D, and 1. 77D) occurred after 2 weeks, 1 month, and 1 month postoperation, respectively, which were significantly higher than those before operation (0.19 +/- 1.32D, 0.12 +/- 1.22D, and 0.17 +/- 1.25D, P < 0.01), respectively. With 12 months gone, they were 0. 03D, -0. 18D, and -0. 13D higher than those before operation, respectively. The rates of function bleb and thin-wall bleb were 71.43% and 26.37% in group A, 75.38% and 29.23% in group B, 72.09% and 25.58% in group C, respectively at 12 months after treatment There were no significant differences among the 3 groups. CONCLUSION: "Straight scleral tunnel incision" -trabeculectomy with a releasable suture supplemented with MMC can reduce complications and get satisfactory results in reducing IOP and SIA.

Aged↗

Synthesis and electrical properties of ZnO nanowires.

Vertically aligned ZnO nanowires were synthesized on the p(+) silicon chip by modifying the CVD process with a vapor trapping design. Scanning electron microscopy was used to investigate the morphology of as-obtained nanowires. X-ray diffraction showed that the obtained nanowires were ZnO crystalline. The rectifying characteristics of the p-n heterojunction composed of ZnO nanowires and a p(+) silicon chip were observed. The positive turn-on voltage was 0.5V and the reverse saturation current was 0.01mA. These vertically aligned ZnO nanowires showed a low field emission threshold of 4V/microm at a current density of 0.1microA/cm(2). The dependence of emission current density on the electric field followed Fowler-Nordheim relationship.

Journal Article↗

Cortical responses to invisible objects in the human dorsal and ventral pathways.

The primate visual system is believed to comprise two main pathways: a ventral pathway for conscious perception and a dorsal pathway that can process visual information and guide action without accompanying conscious knowledge. Evidence for this theory has come primarily from studies of neurological patients and animals. Using fMRI, we show here that even though observers are completely unaware of test object images owing to interocular suppression, their dorsal cortical areas demonstrate substantial activity for different types of visual objects, with stronger responses to images of tools than of human faces. This result also suggests that in binocular rivalry, substantial information in the suppressed eye can escape the interocular suppression and reach dorsal cortex.

Adult↗

Orientation-tuned FMRI adaptation in human visual cortex.

Adaptation is a general property of almost all neural systems and has been a longstanding tool of psychophysics because of its power to isolate and temporarily reduce the contribution of specific neural populations. Recently, adaptation designs have been extensively applied in functional MRI (fMRI) studies to infer neural selectivity in specific cortical areas. However, there has been considerable variability in the duration of adaptation used in these experiments. In particular, although long-term adaptation has been solidly established in psychophysical and neurophysiological studies, it has been incorporated into few fMRI studies. Furthermore, there has been little validation of fMRI adaptation using stimulus dimensions with well-known adaptive properties (e.g., orientation) and in better understood regions of cortex (e.g., primary visual cortex, V1). We used an event-related fMRI experiment to study long-term orientation adaptation in the human visual cortex. After long-term adaptation to an oriented pattern, the fMRI response in V1, V2, V3/VP, V3A, and V4 to a test stimulus was proportional to the angular difference between the adapting and test stimuli. However, only V3A and V4 showed this response pattern with short-term adaptation. In a separate experiment, we measured behavioral contrast detection thresholds after adaptation and found that the fMRI signal in V1 closely matched the psychophysically derived contrast detection thresholds. Similar to the fMRI results, adaptation induced threshold changes strongly depended on the duration of adaptation. In addition to supporting the existence of adaptable orientation-tuned neurons in human visual cortex, our results show the importance of considering timing parameters in fMRI adaptation experiments.

Adaptation, Physiological↗

Protection against influenza virus infection in BALB/c mice immunized with a single dose of neuraminidase-expressing DNAs by electroporation.

The ability of a single dose of plasmid DNA encoding neuraminidase (NA) or hemagglutinin (HA) from influenza virus A/PR/8/34 (PR8) (H1N1) to protect against homologous virus infection was examined in BALB/c mice. In the present study, mice were immunized once with 30 microg of NA or HA DNA by electroporation. Four weeks or 28 weeks after immunization, mice were challenged with a lethal dose of homologous virus and the ability of NA or HA DNA to protect the mice from influenza was evaluated. We found that a single inoculation of NA DNA could provide protection against influenza virus challenge as well as long-term protection against viral infection. Whereas, the mice immunized with a single dose of HA DNA could not be protected. In addition, neonatal mice immunized with a single dose of 30 microg of NA DNA could be provided with significant protection against viral infection.

Animals↗