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Biomedical subjects

Zheng Feng

Publications and source records attributed to Zheng Feng.

At least 19 recordsLinked to original sources

Clonorchis sinensis: development and evaluation of a nested polymerase chain reaction (PCR) assay.

Clonorchis sinensis is a fish-borne trematode endemic to East Asia, which infects over 35 million people globally. In the study described here, we developed a nested polymerase chain reaction (PCR) method for the specific and reliable detection of C. sinensis. The primers designed from the nucleotide sequence data derived in this study were evaluated for their specificity and sensitivity for the detection of C. sinensis. The specific amplification products were obtained only with C. sinensis and no amplifications occurred with the DNA of closely related trematodes including Opisthorchis viverrini demonstrating the specificity of the assay. The novel PCR method described here will be useful for the quarantine of fishery products and evaluation of transmission status of clonorchiasis in the endemic areas.

Animals↗

Reconstruction and in silico analysis of the MAPK signaling pathways in the human blood fluke, Schistosoma japonicum.

At present, little is known about signal transduction mechanisms in schistosomes, which cause the disease of schistosomiasis. The mitogen-activated protein kinase (MAPK) signaling pathways, which are evolutionarily conserved from yeast to Homo sapiens, play key roles in multiple cellular processes. Here, we reconstructed the hypothetical MAPK signaling pathways in Schistosoma japonicum and compared the schistosome pathways with those of model eukaryote species. We identified 60 homologous components in the S. japonciumMAPK signaling pathways. Among these, 27 were predicted to be full-length sequences. Phylogenetic analysis of these proteins confirmed the evolutionary conservation of the MAPK signaling pathways. Remarkably, we identified S. japonicum homologues of GTP-binding protein beta and alpha-I subunits in the yeast mating pathway, which might be involved in the regulation of different life stages and female sexual maturation processes as well in schistosomes. In addition, several pathway member genes, including ERK, JNK, Sja-DSP, MRAS and RAS, were determined through quantitative PCR analysis to be expressed in a stage-specific manner, with ERK, JNK and their inhibitor Sja-DSP markedly upregulated in adult female schistosomes.

Amino Acid Sequence↗

New perspectives on host-parasite interplay by comparative transcriptomic and proteomic analyses of Schistosoma japonicum.

Schistosomiasis remains a serious public health problem with an estimated 200 million people infected in 76 countries. Here we isolated ~ 8,400 potential protein-encoding cDNA contigs from Schistosoma japonicum after sequencing circa 84,000 expressed sequence tags. In tandem, we undertook a high-throughput proteomics approach to characterize the protein expression profiles of a number of developmental stages (cercariae, hepatic schistosomula, female and male adults, eggs, and miracidia) and tissues at the host-parasite interface (eggshell and tegument) by interrogating the protein database deduced from the contigs. Comparative analysis of these transcriptomic and proteomic data, the latter including 3,260 proteins with putative identities, revealed differential expression of genes among the various developmental stages and sexes of S. japonicum and localization of putative secretory and membrane antigens, enzymes, and other gene products on the adult tegument and eggshell, many of which displayed genetic polymorphisms. Numerous S. japonicum genes exhibited high levels of identity with those of their mammalian hosts, whereas many others appeared to be conserved only across the genus Schistosoma or Phylum Platyhelminthes. These findings are expected to provide new insights into the pathophysiology of schistosomiasis and for the development of improved interventions for disease control and will facilitate a more fundamental understanding of schistosome biology, evolution, and the host-parasite interplay.

Amino Acid Sequence↗

Beneficial effects of melatonin in experimental models of Alzheimer disease.

Alzheimer's disease (AD), a progressive degenerative disorder, is characterized by the presence of amyloid deposits, neurofibrillary tangles and neuron loss. Emerging evidence indicates that antioxidants could be useful either for the prevention or treatment of AD. It has been shown that melatonin is a potent antioxidant and free radical scavenger. Additionally, melatonin stimulates several antioxidative enzymes and improves mitochondrial energy metabolism. These findings led us to study amyloid precursor protein transgenic mice, ovariectomized rats, and pheochromocytoma and astroglioma cell lines, to observe whether melatonin had any effect on Alzheimer's symptoms or pathological changes. We found that melatonin had many beneficial effects in experimental models of AD, including improvement of cognitive function, anti-oxidative injury, anti-apoptosis, inhibition of beta-amyloid (Abeta) deposition and Abeta fiber formation. Several groups have shown that melatonin has an inhibitory effect on tau protein hyperphosphorylation. These actions may potentially slow down or stop the progression of dementia.

Alzheimer Disease↗

A drug-based intervention study on the importance of buffaloes for human Schistosoma japonicum infection around Poyang Lake, People's Republic of China.

Schistosomiasis japonica is a zoonosis of major public health importance in southern China. We undertook a drug intervention to test the hypothesis that buffalo are major reservoirs for human infection in the marshlands/lake areas, where one million people are infected. We compared human and buffalo infection rates and intensity in an intervention village (Jishan), where humans and buffalo were treated with praziquantel, and a control village (Hexi), where only humans were treated, in the Poyang Lake region. Over the four-year study, human incidence in Jishan decreased but increased in Hexi. Adjustment of incidence by age, sex, water exposure, year, and village further confirmed the decreased human infection in Jishan. Chemotherapy for buffaloes resulted in a decrease in buffalo infection rates in Jishan, which coincided with the reduction in human infection rates there in the last two years of the study. Mathematical modeling predicted that buffalo are responsible for 75% of human transmission in Jishan.

Adolescent↗

Early melatonin supplementation alleviates oxidative stress in a transgenic mouse model of Alzheimer's disease.

Multiple lines of evidence demonstrated that increased brain oxidative stress is a key feature of Alzheimer's disease (AD). Melatonin is a potent endogenous antioxidant and free radical scavenger. A transgenic mouse model for AD mimics the accumulation of senile plaques, neuronal loss, and memory impairment. Four-month-old transgenic mice were administrated melatonin at 10 mg/kg for 4 months. We investigated the long-term influence of melatonin on these mice before amyloid plaques were deposited. We found an increase in the levels of brain thiobarbituric acid-reactive substances (TBARS) and a decrease in glutathione (GSH) content, as well as accelerated upregulation of the apoptotic-related factors, such as Bax, caspase-3, and prostate apoptosis response-4 (Par-4) in transgenic mice, but not in wild-type (WT) littermates. Significantly, the increase in TBARS levels, reduction in superoxide dismutase activity, and GSH content were reinstated by melatonin. In addition, transgenic mice administered melatonin (10 mg/kg) showed a significant reduction in upregulated expression of Bax, caspase-3 and Par-4, indicating inhibited triggering of neuronal apoptosis. These results supported the hypothesis that oxidative stress was an early event in AD pathogenesis and that antioxidant therapy may be beneficial only if given at this stage of the disease process. In sharp contrast to conventional antioxidants, melatonin crosses the blood-brain barrier, is relatively devoid of toxicity, and constitutes a potential therapeutic candidate in AD treatment.

Alzheimer Disease↗

Long-term melatonin or 17beta-estradiol supplementation alleviates oxidative stress in ovariectomized adult rats.

Melatonin is an endogenously generated potent antioxidant. Our previous results indicated that melatonin improved learning and memory deficits in the transgenic mouse model of Alzheimer's disease (AD) and ovariectomized (OVX) rats by improving cholinergic nerve system dysfunction, preventing apoptosis. In this study we aim to investigate the antioxidative effects of melatonin or estradiol in the brains of ovariectomized rats. OVX Sprague-Dawley rats received daily injections of melatonin (5, 10, or 20 mg/kg), 17beta-estradiol (80 microg/kg), or sesame oil for 16 weeks. We found an increase in brain mitochondrial thiobarbituric acid-reactive substances (TBARS) levels, a decrease in mitochondrial glutathione (GSH) content as well as mitochondrial superoxide dismutase (SOD) activity and upregulation of the apoptotic-related factors, such as Bax, Caspase-3, and Prostate apoptosis response-4 (Par-4) in the frontal cortex of OVX rats. In addition to oxidative stress, OVX also caused decreased activities of mitochondrial respiration complex I and complex IV, which implicated mitochondrial dysfunction. Melatonin or 17beta-estradiol antagonized the detrimental effects induced by OVX. Furthermore, immunohistochemistry results revealed that the abnormal upregulation of the apoptotic related factor such as Bax, Caspase-3, and (Par-4) greatly reduced expression after melatonin or 17beta-estradiol supplement action. These findings demonstrate the important effects of melatonin or 17beta-estradiol on postmenopausal neuropathy and support the potential application of melatonin in the treatment of dementia in postmenopausal women. Early, long-term melatonin application is a promising strategy which could potentially be applied in a clinical setting.

Animals↗

Glomerular aging in females is a multi-stage reversible process mediated by phenotypic changes in progenitors.

The glomeruli of postmenopausal C57BL6 mice, and age-matched males, show progressive hypertrophy and glomerulosclerosis. We asked whether this was a multistage process, was due to alterations in glomerular progenitors, and was reversible in female mice. Using cross bone marrow transplants (BMT) between young and old females, we found that BMT delivered a phenotype that was donor age-specific. The fact that lesions in young recipients were more severe if the donors were in late rather than early menopause suggested that new progenitor phenotypes had appeared. Postmenopausal recipients of BMT from young donors had reduced glomerular hypertrophy and sclerosis, implying that the aging lesions in females were reversible and that progenitors, rather than the local environment, determined the glomerular profile. The altered phenotype included increased extracellular matrix synthesis and decreased matrix metalloproteinase-2 levels as well as cell hypertrophy. The mechanism of the cellular hypertrophy was due to uncoupling of hypertrophy from proliferation, resulting from elevated p27 levels. Thus, glomerular hypertrophy and sclerosis in aging females is a multistage process, is reversible, and may be determined by the phenotype of bone marrow-derived progenitor cells.

Aging↗

A seroepidemiological survey of Taenia solium cysticercosis in Nabo, Guangxi Zhuang Autonomous Region, China.

We have observed the seropositive rate of Taenia solium cysticercosis in residents at Nabo Village, Tiandong County, Guangxi Zhuang Autonomous Region, China by enzyme linked immunosorbent assay. The village had been found to be a relatively high endemic area of porcine cysticercosis among roaming pigs. Of 202 persons examined four males aged 15, 25, 35 and 41 year-old exhibited absorbance (abs) at 0.18, 0.20, 0.35 and 0.55, respectively. In addition, two females whose ages were 35 and 39 years revealed specific antibody levels of abs 0.26 and 0.41 in their sera. Overall positive rate among the people was 2.97%. All of these persons agreed that they had ingested the pork infected with T. solium metacestode (TsM), while history of proglottid discharge was not noticed from all of them. Three males and one female complained of intermittent headache. Our findings reinforced not only that the prevalence of cysticercosis might be related with roaming pigs infected with TsM but also that behavioral and environmental practices in local community constituted risk factors for transmission of the infection.

Adolescent↗

Protective effect of melatonin on beta-amyloid-induced apoptosis in rat astroglioma C6 cells and its mechanism.

Astrocytosis is a common feature of amyloid plaques. The Abeta-astrocyte interaction produces a detrimental effect on neurons, which may contribute to neurodegeneration in Alzheimer disease (AD). The regulation of astrocyte apoptosis is essential to physiological and pathological processes in the CNS. Melatonin is a potent antioxidant and free radical scavenger. Previously, we showed that melatonin alleviated the learning and memory deficits in the APP 695 transgenic mouse model of AD. In this study, the importance of melatonin in the management of Abeta-induced apoptosis in an astrocyte-like cell is discussed. We found that rat astroglioma C6 cells treated with Abeta25-35 or Abeta1-42 undergo apoptosis and that melatonin pretreatment at 10(-5), 10(-6), and 10(-7) M significantly attenuates Abeta25-35- or Abeta1-42-induced apoptosis. The antiapoptotic effects of melatonin were extremely reproducible and corroborated by multiple quantitative methods, including an MTT cell viability assay, Hoechst 33342 nuclei staining, DNA fragmentation analysis, and flow cytometric analysis. In addition, melatonin effectively suppressed Abeta1-42-induced nitric oxide formation, remarkably prevented Abeta1-40-induced intracellular calcium overload, and significantly alleviated Abeta1-40-induced membrane rigidity. Our results demonstrate that, in addition to the beneficial effects of providing direct antioxidant protection to neurons, melatonin may enhance neuroprotection against Abeta-induced neurotoxicity by promoting the survival of glial cells.

Alzheimer Disease↗

[Western blotting analysis of specific antigens from different components of Echinococcus metacestodes].

OBJECTIVE: To analyze antigens for searching specific antigenic components for immunodiagnosis of echinococcosis. METHODS: Fourteen crude antigens from different tissues (cyst fluid, protoscoleces, laminated layer and germinal layer) of Echinococcus granulosus and E. multilocularis metacestodes and other 4 species of cestodes were analyzed by Western blotting. The differences of protein bands were compared for the 14 crude antigens by reacting with pooled sera from cystic echinococcosis (CE) and alveolar echinococcosis (AE) patients. RESULTS: Eleven protein bands from the antigens reacted nonspecifically with sera from both CE and AE patients were Mr 130000, 100000, 94000, 80000, 75000, 66000, 62000, 52000, 38000, 32000, 24000. The highly specific protein bands recognized by AE sera were Mr 120000, 109000, 86000, 59000, 43000, 28000, 20000, 18000, and by CE sera were Mr 41000, 40000, 22000, 16000 and 12000. CONCLUSION: Different antigens shared by the two species of Echinococcus were examined and potential antigenic proteins specific for AE or CE sera were found, providing useful information for further identifying specific antigens for immunodiagnosis.

Animals↗

[The experimental study of histomorphology and biomechanical of cortical strut allograft in proximal femoral].

OBJECTIVE: To explore the deep-frozen allograft strut in the rabbits for the sake of finding some evidence to support the clinical practice of cortical strut allograft. METHODS: Fifty deep-frozen allograft struts were implanted on the lateral side of the femur in 50 male New Zealand white rabbits. These rabbits were randomly divided into 5 groups. The specimen were retrieved at 2, 4, 8, 16, 24 weeks after surgeries. In each group histomorphology and biomechanic properties were studied. RESULTS: From the X ray photography the edge of the strut would turn blunt at the 4th week, union could be found at the 8th week, the inner side of the strut could be absorbed at the 24th week. In the early stage when the strut was implanted in the rabbit, the capillary would be found to grow into the cortical strut from the interior side of it. Then the capillaries were found to converge at the 16th week. This phenomenon is correspondent with the resorption of the dead bone and formation of the new bone. There are few neoformated capillaries on the lateral side of the strut. From the decalcificied section, allograft struts were found to unit to the host at 4 to 8th week. Osteoclast and the new bone formation could be seen at the 8th week, and 3% of the total area of what had been the allograft was replaced by the new bone at that time, 12% was replaced at the 16th week, 21% at the 24th week. There are few resorption or neoformated bone at the lateral side of the strut. The biomechanical property indicated that the strength of the strut decreased at the early time, and only 38% of its original strength remained at 16 weeks. CONCLUSIONS: The cortical allograft strut can unit to the host by the callus. The capillaries invading into the allograft from the interior side, new bone is formed from the interior side. The biomechanical strength of the strut decreased at early stage.

Animals↗

Murine CD45+CD86+ cells isolated from para-aortic lymph nodes in an abortion-prone model.

The present study aims to address whether the analysis of CD45+CD86+ cells isolated from para-aortic lymph nodes (pLNs) is valuable in assessment of the status of local immunity at the murine feto-maternal interface. CBA/J x DBA/2 mice, virgin CBA/J mice, and CBA/J x BALB/c mice were used as an abortion-prone model (group A), nonpregnant controls (group N), and fertile controls (group F), respectively. The percentage of CD45+CD86+ cells in the CD45+ cell group (CD45+CD86+ percentage for short) and the absolute number of these cells were determined by means of flow cytometry (FCM), using mononuclear cells isolated from pLNs collected 5.5, 9.5, and 13.5 days post-coitum (dpc), respectively, and mononuclear cells isolated from placentas 13.5 dpc. To clarify the identity of these CD86+ cells, FCM was also performed with CD3, CD19, and DX5 as specific markers for murine T-cells, B-cells, and NK cells, respectively. Both resorption rate and absolute number of resorptions were significantly higher in group A (29.3%, 1.8+/-1.0) than in group F (4.8%, 0.3+/-0.5, P<0.001, respectively). Similarly, both cell percentage and absolute number of CD45+CD86+ cells in pLNs collected 13.5 dpc were significantly higher in group A than in group F (27.5+/-14.0% versus 12.3+/-7.1%, and 1362+/-687 versus 615+/-353, P=0.001, respectively). The CD45+CD86+ percentage was around 7.5% in nonpregnant CBA/J mice, similar to the 10.6% in CBA/JxDBA/2 mice 5.5 dpc, but had increased dramatically, to 23.9%, by 9.5 dpc (P<0.001 versus nonpregnant mice and P=0.002 versus CBA/JxDBA/2 mice 5.5 dpc), and remained at a higher level (27.5%) until 13.5 dpc. However, this trend was not observed in group F during pregnancy. The increased CD45+CD86+ percentage at day 9.5 of gestation, when resorption begins, may support the assumption that CD45+CD86+ cells play a role in the course of embryo resorption. Lymphocyte phenotypic analysis in the lymph nodes that drain the pregnant uterus may be helpful to assess the status of local immunity at the feto-maternal interface.

Animals↗

Schistosome transcriptomes: new insights into the parasite and schistosomiasis.

Schistosomiasis is one of the most serious parasitic diseases. More than 250 million people are infected with schistosomes in the tropics or subtropics. The parasitic flukes have some unique biological features: dioecism, complex life cycles, mechanisms to avoid host immune responses, and an apparent reliance on host endocrine and immune signals to complete their development, maturation and egg production. Recently, a large dataset of expressed sequence tags (ESTs) were generated from Schistosoma japonicum and Schistosoma mansoni, from which numerous novel genes were identified. The transcriptome analyses provide the basis for a comprehensive understanding of the molecular mechanisms involved in schistosome nutrition and metabolism, host-dependent development and maturation, immune evasion and invertebrate evolution. In addition, new potential vaccine candidates and drug targets have been predicted.

Animals↗

Schistosome transcriptome analysis at the cutting edge.

We live in the era of post-genomics, a term that was, until recently, inappropriate when considering the blood flukes of humans because of the relative lack of knowledge of the schistosome genome. The position has, however, changed dramatically following the recent publication of two landmark papers on transcriptome analysis of Schistosoma japonicum and Schistosoma mansoni. In a quantum leap, both studies report on the identification of many novel genes and genes not previously known from schistosomes. The datasets provide new insights into the biology of the schistosomes and offer an opportunity for identification of potential antischistosome vaccine candidates and drug targets. Remarkable recent progress has also been achieved in genomic sequencing, and completed genomes for both species can be expected shortly.

Animals↗

Melatonin alleviates behavioral deficits associated with apoptosis and cholinergic system dysfunction in the APP 695 transgenic mouse model of Alzheimer's disease.

Melatonin is an endogenous antioxidant and free radical scavenger. A transgenic (Tg) mouse model for Alzheimer's disease mimics the accumulation of senile plaques, neuronal apoptosis and memory impairment. Previous studies indicated that melatonin reduced beta-amyloid (Abeta)-induced neurotoxicity. In this study, after giving melatonin at 10 mg/kg to APP 695 transgenic (APP 695 Tg) mice for 4 months, we evaluated the long-term influence of melatonin on behavior, biochemical and neuropathologic changes in APP 695 Tg mice. Step-down and step-through passive avoidance tests suggested that 8-month-old APP 695 Tg mice showed decreases in step-down latency and step-through latency and increases in count of error throughout the entire learning trial and memory session, which suggested learning and memory impairment. However, melatonin alleviated learning and memory deficits. Additionally, choline acetyltransferase (ChAT) activity also decreased in the frontal cortex and hippocampus of APP 695 Tg mice compared with non-Tg littermates. Melatonin supplementation increased ChAT activity in the frontal cortex and hippocampus. DNA fragmentation was present in the frontal cortex of the APP 695 Tg mice; melatonin reduced the number of apoptotic neurons. Congo Red staining and Bielschowsky silver impregnation both showed the apparent extracellular Abeta deposition in frontal cortex of APP 695 Tg mice. However, melatonin decreased the Abeta deposits. Our results indicate that neuroprotection by melatonin is partly related to modulation of apoptosis and protection of the cholinergic system. Early rational melatonin interventions may be one of the most promising strategies in the development of approaches to retard or prevent Abeta-mediated disease progression.

Alzheimer Disease↗

Long-term effects of melatonin or 17 beta-estradiol on improving spatial memory performance in cognitively impaired, ovariectomized adult rats.

Melatonin is an endogenously generated potent antioxidant. Our previous studies indicate that melatonin improved learning and memory deficits in APP695 transgenic mouse of Alzheimer's disease. An ovariectomized (OVX) rat model which is characterized by progressive memory deficits, central cholinergic nerve system degeneration and differentiation/apoptosis imbalance is the ideal in vivo model in which to test the neuroprotective effects of melatonin. OVX Sprague-Dawley rats received daily injections of melatonin (5, 10 and 20 mg/kg) or 17 beta-estradiol (E2, 80 microg/kg) or sesame oil for 16 wk. Morris water maze results showed that ovarian steroid deprivation resulted in spatial memory impairment, while melatonin and E2 significantly ameliorated spatial memory deficits in OVX rats. The latency to find the hidden platform and the distance to reach the platform become shorter in both melatonin and E2-treated rats compared with those that were only OVX. Four months after OVX, the choline acetyltransferase activity in the frontal cortex and hippocampus were greatly decreased in comparison with the controls. Melatonin and E2 antagonized the effects induced by OVX. Interestingly, the activity of the acetylcholinesterase was not altered in any group of rats. DNA fragmentation was presented in the front cortex of the OVX rats. Melatonin and E2 reduced the number of apoptotic neurons. These findings demonstrate the important effects of melatonin and E2 on cholinergic neurons and support the potential application of melatonin in the treatment of dementia in postmenopausal women. Our results indicate that neuroprotection by melatonin partly correlated to modulation of apoptosis and protection of the cholinergic system. Early long-term melatonin application is a promising strategy which could potentially be applied in a clinic setting.

Alzheimer Disease↗

Melatonin reduces amyloid beta-induced apoptosis in pheochromocytoma (PC12) cells.

The finding that the amyloid beta protein (Abeta) has neurotoxic properties and that such effects are partly mediated by free radicals has provided insights into the mechanisms of cell death in Alzheimer's disease (AD) and an avenue to explore new therapeutic approaches. Melatonin is a potent antioxidant and free radical scavenger. Previously, we showed that long-term application of melatonin alleviated the learning and memory deficits in the APP695 transgenic mouse model of AD. In this study, the importance of melatonin in the management of Abeta-induced apoptosis was investigated. Rat pheochromocytoma (PC12) cells treated with either Abeta25-35 or Abeta1-42 underwent apoptosis. Melatonin pretreatment at 10(-5), 10(-6) and 10(-7) m significantly attenuated Abeta25-35- or Abeta1-42-induced apoptosis in PC12 cells. The anti-apoptotic effects of melatonin were highly reproducible and corroborated by multiple quantitative methods, including MTT cell viability assay, Hoechst 33342 nuclei staining, DNA fragmentation analysis, and flow cytometric analysis. In addition, melatonin effectively suppressed Abeta1-42-induced nitric oxide formation, potently prevented Abeta1-40-induced intracellular calcium overload and significantly alleviated Abeta1-40-induced membrane rigidity. These results suggest that the mechanism of Abeta neurotoxicity involves oxidative stress, and the neuroprotective effects of melatonin are, at least in part, associated with its antioxidant properties. The use of melatonin or its derived analogs should be explored as a therapeutic approach in AD.

Amyloid beta-Peptides↗