Biomedical subjects

Jie Yuan

Publications and source records attributed to Jie Yuan.

At least 19 recordsLinked to original sources

PubMed2025

GATA2 promotes cervical cancer progression under the transcriptional activation of TRIP4.

The continued rise in recurrence and mortality rates of cervical cancer suggests the need to find novel therapeutic targets. Previous studies suggest that TRIP4 acts as a transcription factor to regulate cervical carcinogenesis and progression. Our aim was to explore whether the key downstream genes of TRIP4 functions same as TRIP4 in promoting cervical cancer development. We analyzed and confirmed the downstream targets of TRIP4 by RNA sequencing in cervical cancer cells with TRIP4 knockdown. The expression correlation between TRIP4 and GATA2 and the effect of GATA2 on cervical cancer cell growth were determined respectively by Western Blot, Scratch, Spheroid, and MTT analyses. Pulldown and ChIP experiments were performed to analyze the binding of TRIP4 to the promoter of GATA2. The clinical significance of GATA2 and TRIP4 expression in cervical cancer patients was analyzed by tissue microarray staining. GATA2 was highly expressed in cervical cancer tissues. Knockdown of GATA2 inhibited the growth, metastasis and stemness of cervical cancer cells and sensitized cervical cancer cells to radiation therapy. The inhibitory effect of TRIP4 knockdown on cervical cancer cells was rescued by GATA2 overexpression. Furthermore, TRIP4 could bind to the specific GATA2 promoter region, thereby activating its transcription. Clinical tissue microarray analysis indicated that the expression of TRIP4 and GATA2 was positively correlated, and high expression of both predicted a poor prognosis in cervical cancer patients. Our study demonstrated that GATA2 functions as the key downstream target of TRIP4 to promote cervical cancer progression and effective intervention of TRIP4/GATA2 signaling is expected to be developed as potential cervical cancer therapeutic strategy.

Humans↗

PubMed2024

Abundant mRNA m1A modification in dinoflagellates: a new layer of gene regulation.

Dinoflagellates, a class of unicellular eukaryotic phytoplankton, exhibit minimal transcriptional regulation, representing a unique model for exploring gene expression. The biosynthesis, distribution, regulation, and function of mRNA N1-methyladenosine (m1A) remain controversial due to its limited presence in typical eukaryotic mRNA. This study provides a comprehensive map of m1A in dinoflagellate mRNA and shows that m1A, rather than N6-methyladenosine (m6A), is the most prevalent internal mRNA modification in various dinoflagellate species, with an asymmetric distribution along mature transcripts. In Amphidinium carterae, we identify 6549 m1A sites characterized by a non-tRNA T-loop-like sequence motif within the transcripts of 3196 genes, many of which are involved in regulating carbon and nitrogen metabolism. Enriched within 3'UTRs, dinoflagellate mRNA m1A levels negatively correlate with translation efficiency. Nitrogen depletion further decreases mRNA m1A levels. Our data suggest that distinctive patterns of m1A modification might influence the expression of metabolism-related genes through translational control.

Dinoflagellida↗

PubMed2006

Conservation of the metabolomic response to starvation across two divergent microbes.

We followed 68 cellular metabolites after carbon or nitrogen starvation of Escherichia coli and Saccharomyces cerevisiae, using a filter-culture methodology that allows exponential growth, nondisruptive nutrient removal, and fast quenching of metabolism. Dynamic concentration changes were measured by liquid chromatography-tandem mass spectrometry and viewed in clustered heat-map format. The major metabolic responses anticipated from metabolite-specific experiments in the literature were observed as well as a number of novel responses. When the data were analyzed by singular value decomposition, two dominant characteristic vectors were found, one corresponding to a generic starvation response and another to a nutrient-specific starvation response that is similar in both organisms. Together these captured a remarkable 72% of the metabolite concentration changes in the full data set. The responses described by the generic starvation response vector (42%) included, for example, depletion of most biosynthetic intermediates. The nutrient-specific vector (30%) included key responses such as increased phosphoenolpyruvate signaling glucose deprivation and increased alpha-ketoglutarate signaling ammonia deprivation. Metabolic similarity across organisms extends from the covalent reaction network of metabolism to include many elements of metabolome response to nutrient deprivation as well.

Carbon↗

PubMed2006

Repair of canine mandibular bone defects with bone marrow stromal cells and porous beta-tricalcium phosphate.

Tissue engineering has become a new approach for repairing bone defects. Previous studies have been limited to the use of slow-degradable scaffolds with bone marrow stromal cells (BMSCs) in mandibular reconstruction. In this study, a 30 mm long mandibular segmental defect was repaired by engineered bone graft using osteogenically induced autologous BMSCs seeded on porous beta-tricalcium phosphate (beta-TCP, n=5). The repair of defects was compared with those treated with beta-TCP alone (n=6) or with autologous mandibular segment (n=4). In the BMSCs/beta-TCP group, new bone formation was observed from 4 weeks post-operation, and bony-union was achieved after 32 weeks, which was detected by radiographic and histological examination. In contrast, minimal bone formation with almost fibrous connection was observed in the group treated with beta-TCP alone. More importantly, the engineered bone with BMSCs/beta-TCP achieved a satisfactory biomechanical property in terms of bending load strength, bending displacement, bending stress and Young's modulus at 32 weeks post-operation, which was very close to those of contralateral edentulous mandible and autograft bone (p>0.05). Based on these results, we conclude that engineered bone from osteogenically induced BMSCs and biodegradable beta-TCP can well repair the critical-sized segmental mandibular defects in canines.

Animals↗

PubMed2006

Characterization of a higBA toxin-antitoxin locus in Vibrio cholerae.

Toxin-antitoxin (TA) loci, which were initially characterized as plasmid stabilization agents, have in recent years been detected on the chromosomes of numerous free-living bacteria. Vibrio cholerae, the causative agent of cholera, contains 13 putative TA loci, all of which are clustered within the superintegron on chromosome II. Here we report the characterization of the V. cholerae higBA locus, also known as VCA0391/2. Deletion of higA alone was not possible, consistent with predictions that it encodes an antitoxin, and biochemical analyses confirmed that HigA interacts with HigB. Transient exogenous expression of the toxin HigB dramatically slowed growth of V. cholerae and Escherichia coli and reduced the numbers of CFU by several orders of magnitude. HigB toxicity could be counteracted by simultaneous or delayed production of HigA, although HigA's effect diminished as the delay lengthened. Transcripts from endogenous higBA increased following treatment of V. cholerae with translational inhibitors, presumably due to reduced levels of HigA, which represses the higBA locus. However, no higBA-dependent cell death was observed in response to such stimuli. Thus, at least under the conditions tested, activation of endogenous HigB does not appear to be bactericidal.

Amino Acid Sequence↗

PubMed2006

Kinetic flux profiling of nitrogen assimilation in Escherichia coli.

We present a new method for probing cellular metabolic fluxes that is based on the kinetics of assimilation of isotope-labeled nutrient into a diversity of downstream metabolites. In the case of nitrogen assimilation, half-maximal labeling of most metabolites occurs in 10-300 s. Fluxes measured on the basis of the kinetics of nitrogen assimilation in exponentially growing E. coli agree well with those fluxes predicted to allow optimal biomass production.

Escherichia coli↗

PubMed2006

Separation and quantitation of water soluble cellular metabolites by hydrophilic interaction chromatography-tandem mass spectrometry.

A key unmet need in metabolomics is the ability to efficiently quantify a large number of known cellular metabolites. Here we present a liquid chromatography (LC)-electrospray ionization tandem mass spectrometry (ESI-MS/MS) method for reliable measurement of 141 metabolites, including components of central carbon, amino acid, and nucleotide metabolism. The selected LC approach, hydrophilic interaction chromatography with an amino column, effectively separates highly water soluble metabolites that fail to retain using standard reversed-phase chromatography. MS/MS detection is achieved by scanning through numerous selected reaction monitoring events on a triple quadrupole instrument. When applied to extracts of Escherichia coli grown in [12C]- versus [13C]glucose, the method reveals appropriate 12C- and 13C-peaks for 79 different metabolites.

Amino Acids↗

PubMed2006

Loss of serotonin transporter protein after MDMA and other ring-substituted amphetamines.

We studied in vivo expression of the serotonin transporter (SERT) protein after 3,4-methylenedioxymethamphetamine (MDMA), p-chloroamphetamine (PCA), or fenfluramine (FEN) treatments, and compared the effects of substituted amphetamines to those of 5,7-dihydroxytryptamine (5,7-DHT), an established serotonin (5-HT) neurotoxin. All drug treatments produced lasting reductions in 5-HT, 5-HIAA, and [(3)H]paroxetine binding, but no significant change in the density of a 70 kDa band initially thought to correspond to the SERT protein. Additional Western blot studies, however, showed that the 70 kDa band did not correspond to the SERT protein, and that a diffuse band at 63-68 kDa, one that had the anticipated regional brain distribution of SERT protein (midbrain>striatum>neocortex>cerebellum), was reduced after 5,7-DHT and was absent in SERT-null animals, was decreased after MDMA, PCA, or FEN treatments. In situ immunocytochemical (ICC) studies with the same two SERT antisera used in Western blot studies showed loss of SERT-immunoreactive (IR) axons after 5,7-DHT and MDMA treatments. In the same animals, tryptophan hydroxylase (TPH)-IR axon density was comparably reduced, indicating that serotonergic deficits after substituted amphetamines differ from those in SERT-null animals, which have normal TPH levels but, in the absence of SERT, develop apparent neuroadaptive changes in 5-HT metabolism. Together, these results suggest that lasting serotonergic deficits after MDMA and related drugs are unlikely to represent neuroadaptive metabolic responses to changes in SERT trafficking, and favor the view that substituted amphetamines have the potential to produce a distal axotomy of brain 5-HT neurons.

5,7-Dihydroxytryptamine↗

PubMed2006

Pharmacokinetic profile of single and repeated oral doses of MDMA in squirrel monkeys: relationship to lasting effects on brain serotonin neurons.

A large body of data indicates that (+/-)3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') can damage brain serotonin neurons in animals. However, the relevance of these preclinical data to humans is uncertain, because doses and routes of administration used in animals have generally differed from those used by humans. Here, we examined the pharmacokinetic profile of MDMA in squirrel monkeys after different routes of administration, and explored the relationship between acute plasma MDMA concentrations after repeated oral dosing and subsequent brain serotonin deficits. Oral MDMA administration engendered a plasma profile of MDMA in squirrel monkeys resembling that seen in humans, although the half-life of MDMA in monkeys is shorter (3 vs 6-9 h). MDMA was biotransformed into MDA, and the plasma ratio of MDA to MDMA was 3-5 / 100, similar to that in humans. MDMA accumulation in squirrel monkeys was nonlinear, and plasma levels were highly correlated with regional brain serotonin deficits observed 2 weeks later. The present results indicate that plasma concentrations of MDMA shown here to produce lasting serotonergic deficits in squirrel monkeys overlap those reported by other laboratories in some recreational 'ecstasy' consumers, and are two to three times higher than those found in humans administered a single 100-150 mg dose of MDMA in a controlled setting. Additional studies are needed on the relative sensitivity of brain serotonin neurons to MDMA toxicity in humans and non-human primates, the pharmacokinetic parameter(s) of MDMA most closely linked to the neurotoxic process, and metabolites other than MDA that may play a role.

3,4-Methylenedioxyamphetamine↗

PubMed2006

Babesia microti primarily invades mature erythrocytes in mice.

Babesia microti is a tick-borne red blood cell parasite that causes babesiosis in people. Its most common vertebrate reservoir is the white-footed mouse. To determine whether B. microti invades reticulocytes, as does the canine pathogen B. gibsoni, we infected the susceptible inbred mouse strains C.B-17.scid and DBA/2 with a clinical isolate of B. microti. Staining of fixed permeabilized red blood cells with 4',6'-diamidino-2-phenylindole or YOYO-1, a sensitive nucleic acid stain, revealed parasite nuclei as large bright dots. Flow cytometric analysis indicated that parasite DNA is primarily found in mature erythrocytes that expressed Babesia antigens but not the transferrin receptor CD71. In contrast, CD71-positive reticulocytes rarely contained Babesia nuclei and failed to express Babesia antigens. Accordingly, the frequency of YOYO-1-positive, CD71-negative cells strongly correlated with parasitemia, defined as the frequency of infected red blood cells assessed on Giemsa-stained blood smears. Importantly, the absolute numbers generated by the two techniques were similar. Parasitemia was modest and transient in DBA/2 mice but intense and sustained in C.B-17.scid mice. In both strains, parasitemia preceded reticulocytosis, but reticulocytes remained refractory to B. microti. In immunocompetent C.B-17 mice, reticulocytosis developed early, despite a marginal and short-lived parasitemia. Likewise, an early reticulocytosis developed in resistant BALB/cBy and B10.D2 mice. These studies establish that B. microti has a tropism for mature erythrocytes. Although reticulocytes are rarely infected, the delayed reticulocytosis in susceptible strains may result from parasite or host activities to limit renewal of the mature erythrocyte pool, thereby preventing an overwhelming parasitemia.

Animals↗

PubMed2006

[Repair of canine segmental mandibular defects using autogenous bone marrow stromal cells and coralline hydroxyapatite].

OBJECTIVE: To repair segmental mandibular defects with autogenous bone marrow stromal cells (BMSCs) and coralline hydroxyapatite. METHODS: Isolated BMSCs were in vitro expanded and osteogenically induced. In 11 canines, a 3 cm segmental mandibular defect in right mandible was created. Five canine's defects were repaired with cell-scaffold constructs made from induced BMSCs and coralline hydroxyapatite (CHA); Others were repaired with CHA as control. The engineered bone was evaluated by X-ray, CT, gross and histological examination, biomechanical test 12, 26, 32 weeks post-operation respectively. RESULTS: BMSCs grew well on the CHA. X-ray and CT images showed better callus formation at connection sites in experimental group over time while worse formation at connection sites eventually in control group. At 32 weeks post-operation in experimental group, the defects were well repaired grossly. Histologically, there were bony healing and lamellar bone formation, in experimental group fibrous healing and woven bone formation in control group. Biomechanical test revealed no significant difference between experimental group and normal control group. CONCLUSIONS: Canine segmental mandibular defects can be ultimately repaired with the tissue-engineered bone generated by autogenous osteogenic BMSCs and CHA scaffold.

Animals↗

PubMed2005

Relationship between temperature, dopaminergic neurotoxicity, and plasma drug concentrations in methamphetamine-treated squirrel monkeys.

To examine the relationship between temperature (ambient and core), dopaminergic neurotoxicity, and plasma drug [methamphetamine (METH)] and metabolite [amphetamine (AMPH)] concentrations, two separate groups of squirrel monkeys (n = 4-5 per group) were treated with METH (1.25 mg/kg, given twice, 4 h apart) or vehicle (same schedule) at two different ambient temperatures (26 and 33 degrees C). Core temperatures and plasma drug concentrations were measured during the period of drug exposure; striatal monoaminergic neuronal markers in the same monkeys were determined 1 week later. At the temperature range examined, the higher ambient temperature did not significantly enhance METH-induced hyperthermia or METH-induced dopaminergic neurotoxicity, although there were trends toward increases. Acute METH-induced increases in core temperature correlated highly and directly with subsequent decreases in striatal dopaminergic markers. Squirrel monkeys with the greatest increases in core temperature (and largest dopaminergic deficits) had the highest plasma drug metabolite (AMPH) concentrations. There was substantial interanimal variability, both with regard to elevations in core temperature and plasma drug concentrations. Pharmacokinetic studies in six additional squirrel monkeys revealed comparable individual differences in METH metabolism. These results, which provide the first available data on the within-subject relationship between temperature (ambient and core), plasma concentrations of METH (and AMPH), and subsequent dopaminergic neurotoxic changes, suggest that, as in rodents, core temperature can influence METH neurotoxicity in primates. In addition, they suggest that interanimal differences presently observed in thermal and neurotoxic responses to METH may be related to individual differences in drug metabolism.

Animals↗

PubMed2005

Amphetamine treatment similar to that used in the treatment of adult attention-deficit/hyperactivity disorder damages dopaminergic nerve endings in the striatum of adult nonhuman primates.

Pharmacotherapy with amphetamine is effective in the management of attention-deficit/hyperactivity disorder (ADHD), now recognized in adults as well as in children and adolescents. Here we demonstrate that amphetamine treatment, similar to that used clinically for adult ADHD, damages dopaminergic nerve endings in the striatum of adult nonhuman primates. Furthermore, plasma concentrations of amphetamine associated with dopaminergic neurotoxicity in nonhuman primates are on the order of those reported in young patients receiving amphetamine for the management of ADHD. These findings may have implications for the pathophysiology and treatment of ADHD. Further preclinical and clinical studies are needed to evaluate the dopaminergic neurotoxic potential of therapeutic doses of amphetamine in children as well as adults.

Amphetamine↗

PubMed2004

Genetic diversity of small eukaryotes from the coastal waters of Nansha Islands in China.

Population structures and genetic diversity of the small eukaryotic plankton from the coastal waters of the Nansha Islands in China were investigated. Two genes libraries using 18S rDNA of the marine small eukaryotes were constituted, and 323 clones were identified within alveolates (more than 43%), acanthareas, viridiplantaes, and stramenopiles. Many novel clones were detected in the two libraries, including two groups of alveolates and two clades related to both acanthareas and polycystineas. Several sequences unrelated to any other known eukaryotes may represent early branches in the phylogenetic tree. Our results reveal that there is a high diversity and abundance of small eukaryotes in the marine regions of China.

Biodiversity↗

PubMed2004

Identification and characterization of metallothionein-1 and -2 gene expression in the context of (+/-)3,4-methylenedioxymethamphetamine-induced toxicity to brain dopaminergic neurons.

In mice, the recreational drug (+/-)3,4-methylenedioxymethamphetamine [MDMA ("ecstasy")] produces a selective toxic effect on brain dopamine (DA) neurons. Using cDNA microarray technology in combination with an approach designed to facilitate recognition of relevant changes in gene expression, the present studies sought to identify genes potentially involved in murine MDMA-induced toxicity to DA neurons. Of 15,000 mouse cDNA fragments studied, metallothionein (Mt)-1 and Mt2 emerged as candidate genes possibly involved in MDMA-induced toxicity to DA neurons. Northern blot analysis confirmed the microarray findings and revealed a dynamic upregulation of Mt1 and Mt2 mRNA in the ventral midbrain within 4-12 hr after MDMA treatment. Western blot analysis showed a similar increase in MT protein levels, with peak times occurring subsequent to increases in mRNA levels. Mt1-2 double knock-out mice were more vulnerable to MDMA-induced toxicity to DA neurons than corresponding wild-type mice. Stimulation of endogenous expression of MT protein with zinc acetate conferred complete protection against MDMA-induced toxicity to DA neurons, and administration of exogenous MT protein afforded partial protection. Collectively, these results indicate that MDMA-induced toxicity to DA neurons is associated with increased Mt1 and Mt2 gene transcription and translation, possibly as part of a neuroprotective mechanism. The present findings may have therapeutic implications for neuropathological conditions involving DA neurons.

3,4-Methylenedioxyamphetamine↗

PubMed2004

Behavioral and neurochemical consequences of long-term intravenous self-administration of MDMA and its enantiomers by rhesus monkeys.

The effects of self-administered 3,4-methylenedioxymethamphetamine (MDMA) on behavior and neurochemistry have not been previously studied in laboratory primates. We investigated the capacity of MDMA and its enantiomers to maintain contingent responding over an extended duration, whether any decrements in the reinforcing effects of these compounds would be observed over time, whether such decrements would be MDMA-selective, and whether any neurochemical correlates could be identified. Animals were previously trained to self-administer cocaine, then exposed to periodic substitutions of various doses of racemic MDMA and its enantiomers; full dose-effect curves were generated for each MDMA compound repeatedly over the duration of the study. After approximately 18 months of MDMA self-administration, drug exposure was halted and after at least 2 months drug abstinence, animals were scanned using positron emission tomography (PET) with the vesicular monoamine transporter (VMAT) ligand dihydrotetrabenazine (DTBZ). Shortly thereafter, animals were euthanized, brains were dissected, and samples were assayed for brain monoamines and their metabolites using high-performance liquid chromatography (HPLC), and for VMAT using DTBZ binding. The reinforcing effects of racemic and R(-)-MDMA were reduced over a long series (months) of individual self-administration access periods; the reinforcing effects of S+-MDMA were more resistant to this effect, but were attenuated for one animal. The reinforcing effects of cocaine were not altered by chronic MDMA self-administration, nor was the VMAT binding potential as assessed by PET. Further, there were no measurable decrements in serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) or VMAT in any brain regions assayed. The reinforcing effects of MDMA are selectively attenuated by chronic MDMA self-administration, although this behavioral change appears to occur in the absence of any frank neurochemical correlates of toxicity.

Animals↗

PubMed2004

[Protective immune mechanisms induced by cellular vaccine made of the erythrocytic Plasmodium yoelii].

OBJECTIVE: To explore the characteristics of protective immunity against Plasmodium yoelii (P.y.) infection by asexual blood-stages cellular vaccine. METHODS: The particulate vaccines were constructed by saponin or double-distilled-water lysed parasitic red blood cells and inoculated into BALB/c mice by intraperitoneal injection (i.p.). Each group was challenged by the lethal erythrocytic P.y. parasites, and then their parasitemia and survival rates were detected. Expressions of interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) were detected by RT-PCR. ELISA showed the serum antibodies against the malaria challenge and their-subclasses. Special membrane protein was recognized by immunofluorescence assay. RESULTS: The vaccination with saponified erythrocytic parasites protected the immunized mice against P.y. challenge, while double-distilled-water lysed vaccine did not (P < 0.01). This protection was characterized by the increase of both IFN-gamma/IgG2a and IL-4/IgG1. Meanwhile, MHC class I alpha chain molecule was recognized on the membrane of infected-erthythrocyte. CONCLUSION: Saponified P.y. asexual blood-stage cellular vaccine has a significantly high protective immunity against this lethal P.y. malaria, and the immunity may be associated with the expression levels of IgG2a and IFN-gamma. MHC class I alpha chain on infected erythrocytes may play an important role in the successful immunization.

Animals↗

PubMed2004

[Immunity of peritoneal monocytes against Plasmodium yoelii infected erythrocytes].

OBJECTIVE: To test the immunity of peritoneal monocytes against Plasmodium yoelii infected red blood cells (target cells). METHODS: Saponinized Plasmodium yoelii infected red blood cells (SPRBC, Ghost erythrocyte) were used to immunize mice i.p twice. Three weeks later, the infected red blood cells were injected i.p.; 90 min later, the total peritoneal cells were isolated and washed for scanning electromicroscopy to observe the effects of the peritoneal monocyte to the target cell. RESULTS: The peritoneal cells of the immunized mice were activated after 90 min of the challenge of target cells. The size of the cell was not even and the pili on the cell surface turned to be long and densed. Cell interconnections were found among the cells. In some peritoneal monocytes, their cell plasma were scattered (omlette-like) or with the shape as "cellular bomb". The scattered or the sheeted pili and spredding cell plasma could adhere to the target cells which were perforated densely and damaged. CONCLUSION: The protective adaptive immunity exists in the peritoneal monocytes of immunized mice.

Animals↗