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Biomedical subjects

Gao Chen

Publications and source records attributed to Gao Chen.

At least 19 recordsLinked to original sources

Cooperative anaerobic catabolism of chlorinated organic compounds: implications for sustainable bioremediation.

Biodegradation research historically followed a reductionist approach focused on axenic (pure) cultures capable of catabolizing the specific contaminant(s) of interest. While this approach has substantially advanced our understanding of the microbiology, physiology, biochemistry, and genetics of contaminant degradation under laboratory conditions, it does not capture the complexity of natural and engineered environments. During in situ bioremediation, microbiomes are exposed to mixtures of contaminants, and microbial interactions profoundly influence contaminant transformation and fate. In anoxic environments, degradation of chlorinated compounds is often sustained by metabolic cooperation among taxonomically and physiologically distinct microorganisms. Through the exchange of metabolites such as hydrogen, formate, acetate, and other nutrients, microbial populations establish interdependent networks that overcome thermodynamic and physiological constraints, enabling self-sustaining systems of contaminant transformations that would be inefficient or impossible with individual organisms. We highlight examples of microbial interactions that underpin anaerobic catabolism of chlorinated contaminants, including systems resulting in self-sustained anaerobic bioremediation.

Biodegradation, Environmental↗

Systematic understanding of mechanism of Shenfu decoction improve the prognosis of ischemic stroke using a network pharmacology and animal experiment approach.

OBJECTIVE: To explore the active compounds and the mechanism of Shenfu decoction (, SFD) against ischemic stroke (IS) through network pharmacology and animal experiments. METHODS: SFD components were retrieved from the Traditional Chinese Medicine (TCM) database. The Online Mendelian Inheritance in Man (OMIM), Comparative Toxicogenomics Database (CTD) and Therapeutic Target Database (TTD) database were used to retrieve the IS-related disease targets. The herb-compound-target network was built by Cytoscape 3.7.1 software. The core targets were obtained using protein-protein interaction (PPI) network. The core targets of SFD were further analyzed through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). We then performed molecular docking between the hub proteins and key active compounds. Finally, we conducted animal experiments to verify the regulation of SFD on apoptosis following IS. RESULTS: There were 221 corresponding targets and 25 components related to Chinese medicine throughout the compound-target network. The core targets of SFD in the treatment of IS was tumor protein P53 (Tp53), mitogen-activated protein kinase 3 (MAPK3), MAPK1, heat shock proteins 90AA1 and alpha serine/threonine-protein kinase1. There were 221 GO items in GO function enrichment analysis and 106 signaling pathways in KEGG, mainly including negative regulation of the apoptosis process, vascular endothelial growth factor signaling pathways, NOD-like receptor signaling pathway, etc. Among them, Tp53, MAPK3, and MAPK1 were docked with small molecule compounds. Through animal research, we confirmed the effect of SFD on apoptosis following stroke. CONCLUSION: This study demonstrates that SFD can treat IS through multiple targets and pathways, and provides new perspectives for exploring the core targets and mechanisms of SFD against IS.

Drugs, Chinese Herbal↗

Menin localizes to chromatin through an ATR-CHK1 mediated pathway after UV-induced DNA damage.

BACKGROUND: Menin is the tumor suppressor protein product of the gene identified in MEN1 syndrome. Evidence suggests menin binds DNA and interacts with proteins implicated in DNA damage pathways. The canonical cellular response to UV-induced DNA damage involves activation of the ataxia-telangiectasia-mutated and Rad3-related (ATR) kinase pathway. MATERIALS AND METHODS: HEK293 cells were irradiated in a UV chamber. Menin's cellular location before and after UV irradiation was investigated by extracting four separate cellular components--a soluble, two chromatin and a nuclear matrix. To block the ATR pathway, we treated with 5 microM of caffeine for 1 h before irradiation. The ATR pathway was further investigated by transiently transfecting HEK293 cells with two mammalian CHK1 expression constructs--full length CHK1 and truncated active CHK1. RESULTS: A 24-h post UV-irradiation time course was studied and demonstrated menin concentration in the chromatin peaked at 4 h. At 4 h post-irradiation, menin concentration in the chromatin increased in a dose dependent manner and demonstrated a 2.8-fold maximal increase. HEK293 cells were pretreated with caffeine, an inhibitor of the ATR. Caffeine decreased menin localization to the chromatin after UV. Constitutively active CHK1 (1-365) transfection increased chromatin-bound menin, mimicking UV irradiation. CONCLUSIONS: Menin localizes to the chromatin after UV irradiation. Caffeine blocks menin localization to the chromatin after UV-irradiation. Over expressing active CHK1 (1-365) increased chromatin-bound menin, similar to UV. The data suggest menin localization to chromatin after UV irradiation is the result of an ATR-CHK1 dependent pathway.

Ataxia Telangiectasia Mutated Proteins↗

Development of antibody-based assays for omega-conotoxin MVIIA.

Omega-conotoxin MVIIA (CTX MVIIA) is a specific peptide blocker of the N-type voltage-sensitive calcium channel in neurons. The synthetic version of CTX MVIIA, Ziconotide, has been recently approved by FDA for management of severe and chronic pains. Currently, the chemical synthetic CTX MVIIA has been analyzed by RP-HPLC, and there are no chemical or immunological assays available for determination of the peptide. In this article, we report a novel method for preparation of polyclonal antibody against CTX MVIIA, and the antibody-based assays for the analysis of CTX MVIIA. The DNA sequences encoding the conotoxin were chemically synthesized and then cloned into the expression vector pGEX-2T. The GST fusion protein of CTX MVIIA was expressed in E. coli BL21 (DE3) with induction of IPTG. The purified fusion protein was used to immunize the male rabbits with standard protocols. The produced antiserum was purified through anion-exchange chromatography. Another thioredoxin (Trx) fusion protein of CTX MVIIA was employed to cross-examine the antibody against the conotoxin. Our Western blot and ELISA results show that the polyclonal antibody was capable of binding the conotoxin parts of both GST and Trx fusion proteins, and the antibody titer is 1:8192. Thus, the assays based on this antibody are useful for the conotoxin analysis.

Animals↗

[Relationship between cerebral vasospasm and delayed ischemic neurological deficit].

OBJECTIVE: To investigate the relationship between cerebral vasospasm and occurrence of delayed ischemic neurological deficit (DIND). METHODS: The clinical records and radiographic images of 118 patients with subarachnoid hemorrhage admitted during last 5 years were reviewed. The incidence,degree and localization of cerebral vasospasm were evaluated, and morbidity of related DIND was analyzed. Patients with cerebral vasospasm were divided into three groups: Group MCA (middle cerebral artery), Group ACA (anterior cerebral artery) and Group ICA (intracranial carotid artery) according to the location of cerebral vasospasm. The consistency of DIND and image of cerebral infarction were examined. RESULT: There was a weak correlation between cerebral vasospasm and incidence of DIND (r=0.22; P=0.016). The incidence of DIND was increased with severity of cerebral vasospasm (U=2.589, P<0.05). The group MCA had a significantly higher incidence of DIND than that of ACA and ICA groups (68.0% compared with 36.7% and 25.0%, respectively, chi(2)=8.195, P=0.004), the difference between later two groups was not statistically significant (chi(2)=0.646, P=0.421). CONCLUSION: Cerebral vasospasm may be an important factor leading to DIND occurrence; the severity and location of cerebral vasospasm is related to the incidence of DIND.

Adult↗

An in vitro culturing model for rabbit dural cells.

The objectives of this study were (a) to construct an in vitro model of rabbit dural healing, (b) to test the influence of collagen, laminin, and poly-L-lysine on the migration and proliferation of dural cells, and (c) to study the healing mechanism of duraplasty. Rabbit dural pieces (1.5 cm x 1.5 cm) were perforated in their central part with a 2 mm punch to mimic a dural defect. The dural pieces were cultured in 24-well plates that had been coated with collagen, laminin, or poly-L-lysine, and the influence of different extracellular matrices on migration and proliferation of dural cells was observed. Cells were subcultured on slides for immunocytochemistry to study their characteristics; dural healing was observed by scanning electron microscopy. The results demonstrated that only the dural pieces that were cultured on collagen-coated wells showed migration of cells into the central defect after a period of 8 to 10 days and that healing of the dural defect occurred by 13 to 15 days. The cultured dural cells stained strongly positive with an antibody to vimentin, but negative with an antibody to factor VIII. New collagen fibers were observed in the dural defects. This report demonstrates that an in vitro model for dural healing was successfully constructed in collagen-coated wells; the results implicate cellular migration of fibroblasts from the dural defect margin as an important mechanism of wound healing following duraplasty.

Animals↗

[Effect of losartan on sarcoplasmic reticulum Ca2+ handing proteins in heart failure rabbit].

OBJECTIVE: To investigate the effects of losartan on mRNA expression of myocardial sarcoplasmic reticulum calcium handling proteins (SERCA2, RyR2 and PLB) and the role of which in prevention of chronic heart failure in rabbit. METHODS: After chronic heart failure was induced by ligation of the left anterior descending artery in rabbits, the animals were treated with losartan. At 8 weeks after ligation, left ventricular function, hemodynamic parameters, and SERCA2, RyR2, PLB mRNA expressions were observed. RESULTS: Compared with the control group (group C), LVEDP in the infarcted group (group I) increased (P < 0.01), while +dp/dt(max) and -dp/dt(max) decreased significantly (P < 0.01). LVEDP was lower but +dp/dt(max) and -dp/dt(max) significantly higher in the losartan treated group (group L) than those in group I (P < 0.05). SERCA2, RyR2, and PLB mRNA expressions in group I were remarkably lower than those in group L (P < 0.01) and group C (P < 0.01), respectively. CONCLUSION: Losartan can improve cardiac function, probably owing to its upregulating mRNA expressions of myocardial sarcoplasmic reticulum Ca(2+) handling proteins (RyR2, SERCA2 and PLB) in the prevention of heart failure.

Angiotensin II Type 1 Receptor Blockers↗

R1, a novel repressor of the human monoamine oxidase A.

Monoamine oxidase catalyzes the oxidative deamination of a number of neurotransmitters. A deficiency in monoamine oxidase A results in aggressive behavior in both humans and mice. Studies on the regulation of monoamine oxidase A gene expression have shown that the Sp1 family is important for monoamine oxidase A expression. To search for novel transcription factors, the sequences of three Sp1 sites in the monoamine oxidase A core promoter were used in the yeast one-hybrid system to screen a human cDNA library. A novel repressor, R1 (RAM2), has been cloned. The R1 cDNA encodes a protein with 454 amino acids and an open reading frame at the 5'-end. The transfection of R1 in a human neuroblastoma cell line, SK-N-BE (2)-C, inhibited the monoamine oxidase A promoter and enzymatic activity. The degree of inhibition of monoamine oxidase A by R1 correlated with the level of R1 protein expression. R1 was also found to repress monoamine oxidase A promoter activity within a natural chromatin environment. A gel-shift assay indicated that the endogenous R1 protein in SK-N-BE (2)-C cells interacted with the R1 binding sequence. R1 also bound directly to the natural monoamine oxidase A promoter in vivo as shown by chromatin immunoprecipitation assay. Immunocytochemical analysis showed that R1 was expressed in both cytosol and nucleus, which suggested a role for R1 in transcriptional regulation. Northern blot analysis revealed the presence of endogenous R1 mRNA in human brain and peripheral tissues. Taken together, this study shows that R1 is a novel repressor that inhibits monoamine oxidase A gene expression.

Amino Acid Sequence↗

Effect of modified Sinisan on anorectal manometry of the constipation predominant type of irritable bowel syndrome.

OBJECTIVE: To explore the mechanism in patients with irritable bowel syndrome (IBS) of the constipation predominant type and observe the therapeutic effects of Sinisan (SNS). METHODS: Forty-seven IBS patients with the constipation predominant type were randomly divided into the treated group (n = 24) and the control group (n = 23). Another group of 22 healthy subjects was set up for healthy control. The treated group was treated with modified SNS, and the control group was treated with Cisapride, the therapeutic course for both groups was 8 weeks. The changes of symptom scoring and anorectal manometry (the anorectal resting pressure, anal tract systolic pressure, anal tract diastolic pressure, rectal threshold feeling, maximal tolerance volume of rectum, and rectum compliance) of these two groups were recorded respectively and compared with each other. RESULTS: Compared with the healthy control group, the rectal threshold feeling, maximal tolerance volume of rectum and rectal compliance of the treated groups got reduced significantly before treatment (P < 0.05). After treatment, the symptom scoring, rectal threshold feeling and maximal tolerance volume of rectum were improved in both groups (P < 0.05), and the improvement of the treated group was more significant than that of the control group (P < 0.01). The total effective rate and recurrence rate of the treated group were superior to those of the control group significantly (P < 0.05, P < 0.01). CONCLUSION: SNS has good effect on IBS of the constipation predominant type.

Adult↗

Distribution of cysteinyl leukotriene receptor 2 in human traumatic brain injury and brain tumors.

AIM: To determine the distribution of cysteinyl leukotriene receptor 2 (CysLT2), one of the cysteinyl leukotriene receptors, in human brains with traumatic injury and tumors. METHODS: Brain specimens were obtained from patients who underwent brain surgery. CysLT2 in brain tissues was examined using immunohistochemical analysis. RESULTS: CysLT2 was expressed in the smooth muscle cells (not in the endothelial cells) of arteries and veins. CysLT2 was also expressed in the granulocytes in both vessels and in the brain parenchyma. In addition, CysLT2 was detected in neuron- and glial-appearing cells in either the late stages of traumatic injury or in the area surrounding the tumors. Microvessels regenerated 8 d after trauma and CysLT2 expression was recorded in their endothelial cells. CONCLUSION: CysLT2 is distributed in vascular smooth muscle cells and granulocytes, and brain trauma and tumor can induce its expression in vascular endothelial cells and in a number of other cells.

Adolescent↗

[Assessing forest ecosystem health II. A case study].

On the bases of samples investment and related data collected by others, and with the method of health distance assessment and the ecosystem health index system of Korean pine and broad-leaved mixed forest established in prior paper, this paper attempted to assess the ecosystem health of Korean pine and broad-leaved mixed forest under various human disturbances. The results showed that the health degree was in the order of 20% intensity selective cutting stand (0.21) < 50% intensity selective cutting stand (0.44) < middle and mature birch stand (0.67) < youth birch stand (0.72) < Korean pine plantation (0.74) < larch plantation (0.77).

Biomass↗

[Clinical applications of devitalized autogenous calvarial bone flaps fixed with titanium clamps (CranioFix) for cranioplasty].

OBJECTIVE: To evaluate reimplantation of devitalized autogenous calvarial bone flaps and the fixation of titanium clamps (CranioFix) for cranioplasty. METHODS: From March 2000 to December 2003, 21 patients underwent (1) delayed reimplantation of preserved autogenous bone flaps, which were removed during the initial operations for increased intracranial pressure and stored in a freezer and autoclaved before use, or (2) immediate reimplantation of tumor invaded bone flaps that were devitalized by boiling. All of these flaps were fixed with titanium clamps (CranioFix). Resorption of the bone flaps was monitored by skull roentgenograms and computed tomography (CT). The clinical and aesthetic results were evaluated. RESULTS: During the follow-up period of 6 to 30 months, no complications were found. There was slight resorption of the bone flaps in all cases, but the edge of the bone flaps was within the range of the titanium clamps according to skull roentgenograms and CT. Clinical and aesthetic results were highly satisfactory. CONCLUSIONS: It is simple and practical using devitalized autogenous calvarial bone flaps for cranioplasty. The firmness decreasing of the reimplanted bone flap due to resorption can be prevented greatly by titanium clamps (CranioFix).

Adolescent↗

Characterization of the expression of key adenoviral receptors CAR and integrin beta3/beta5 subunits on the membrane of human NT2 neurons.

Expression of therapeutic gene products in differentiated human NT2 neurons (NT2/Ns) is being explored for ex vivo gene therapy of human neurological diseases. In this study we determined the efficiency of adenovirus (Ad)-mediated gene delivery into NT2/Ns and characterized the expression of several key receptors known to be required for efficient Ad-mediated gene delivery. Undifferentiated NT2 cells and NT2/Ns were infected by Ad expressing green fluorescent protein at an efficiency of 33% and 17%, respectively percentages much lower than the 92% infectivity obtained from a human non-neuronal cell line A549 cells. This relatively low infectivity of NT2/Ns might be caused by the extremely low expression of integrin subunit beta3 and the reduced expression of beta5 during differentiation. The expression of coxsackie-Ad receptor (CAR) was relatively high and remained constant during differentiation. Blocking CAR receptor using an antibody specific against CAR reduced Ad infectivity in a dose-dependent manner. These observations suggest that modulating the expression of integrin subunits beta3/5 or the functional heterodimer alphavbeta3/5 in human NT2/Ns may enhance adenoviral infectivity of NT2/Ns.

Adenoviridae↗

[Effects of physical and chemical properties of polymeric nerve conduit on peripheral neuranagenesis].

OBJECTIVE: To evaluate the effects of degradation time and permeability of polymeric conduits on nerve regeneration. METHODS: After establishment of rat models with over 10 mm gap of sciatic nerve in right hind legs,four kinds of poly (ester, carbonate) nerve conduits was used to bridge the gaps and one group without conduit in gaps was used as control. The nerve regeneration and conduit degradation were examined both macroscopically and microscopically. The contraction of the muscle controlled by regenerated nerve was measured electrophysiologically at 4, 12 and 20 weeks after the operation. RESULT: Biodegradation time of nerve conduits in vivo was as fellows: 12 weeks in group A,4 weeks in group B and group C,and 20 weeks in group D,respectively. The histological quality of regenerative sciatic neurofibra in group A was the best among all groups (Mean rank 53.17, 38.83, 26. 60, 49.17 and 20.23,P<0.005), but the inflammatory reaction in group A was only less than that in group D and more than that in the other groups (Mean rank 45.87, 36.27, 34. 83, 51.63 and 21.4,P=0.001). The responsive rates of tibialis anterior muscle for electric stimulation in group A, B, C and D were 93.33%, 60%,20% and 73. 33%, respectively (P<0.005). CONCLUSION: Absorbable conduits with relatively good permeability and appropriate middle degrade time improve nerve regeneration and renovate function.

Action Potentials↗

[Assessing forest ecosystem health I. Model, method, and index system].

Ecosystem health assessment is one of the main researches and urgent tasks of ecosystem science in 21st century. An operational definition on ecosystem health and an all-sided, simple, easy operational and standard index system, which are the foundation of assessment on ecosystem health, are necessary in obtaining a simple and applicable assessment theory and method of ecosystem health. Taking the Korean pine and broadleaved mixed forest ecosystem as an example, an originally creative idea on ecosystem health was put forward in this paper based on the idea of mode ecosystem set and the idea of forest ecosystem health, together with its assessment. This creative idea can help understand what ecosystem health is. Finally, a formula was deduced based on a new effective health assessment method--health distance (HD), which is the first time to be brought forward in China. At the same time, aiming at it's characteristics by status understanding and material health questions, a health index system of Korean pine and broadleaved mixed forest ecosystem was put forward in this paper, which is a compound ecosystem based on the compound properties of nature, economy and society. It is concrete enough to measure sub-index, so it is the foundation to assess ecosystem health of Korean pine and broadleaved mixed forest in next researches.

Ecosystem↗

[Structure characteristics and health distance assessment of various disturbed communities of Korean pine and broadleaved mixed forest in Changbai Mountains].

Through samples investigation, this paper analyzed and classified the community structures of overcutting original forests, secondary birch forests and larch plantation forest under different disturbances. At the same time, some indexes which can reflect the integrity and stability of stand structure were selected. Health Distance (HD) method, a new idea, was attempted to assess ecosystem health of Korean pine and broadleaved mixed forest in Changbai Mountains. The results showed that the health degree was in order of original broadleaved stand (0.14) < structure switched stand (0.23) < structure reserved stand (0.32) < structure destroyed stand (0.33) < heavy disturbed stand (0. 44) < secondary birch stand (0.53) < larch plantations (0.68). Hopefully, it will be a helpful reference on the restoration of Korean pine and broadleaved mixed forest and on the regional forestry sustainable development.

China↗