Biomedical subjects

Yan Yu

Publications and source records attributed to Yan Yu.

At least 19 recordsLinked to original sources

PubMed2026

Mitochondrial genome characteristics and phylogenetic analysis of Ramaria longispora.

This study, for the first time, assembled and annotated the complete mitochondrial genome of R. longispora using high-throughput sequencing technology. The genome is a circular molecule with a total length of 157,712 bp and a GC content of 31.55%. It encodes 71 genes, including 15 core protein-coding genes (PCGs), 25 transfer RNA (tRNA) genes, 2 ribosomal RNA (rRNA) genes, 5 free-stranding open reading frames (ORFs), and 24 intronic ORFs. Among these, most free-stranding ORFs have unknown functions but include a DNA polymerase gene, while the intronic ORFs primarily encode LAGLIDADG and GIY-YIG endonucleases. The mitochondrial genome contains 39 introns. Phylogenetic analyses based on 15 core PCGs using Bayesian inference (BI) and maximum likelihood (ML) methods revealed that this R. longispora is most closely related to Ramaria flavescens and Ramaria ichnusensis. This study provides foundational data for mitochondrial genome research in the Ramaria genus and offers important references for taxonomic and evolutionary studies of this group.

Mitochondrial genome↗

PubMed2026

Patient-reported outcomes with tarlatamab in extensive-stage small cell lung cancer after platinum-based chemotherapy: results from the phase 3 DeLLphi-304 trial.

BACKGROUND: Extensive-stage small cell lung cancer (ES-SCLC) is associated with a high symptom burden and impaired health-related quality of life (HRQoL). This prespecified analysis from the phase 3 DeLLphi-304 trial evaluated patient-reported outcomes (PROs) for tarlatamab versus standard-of-care (SoC) chemotherapy following first-line platinum-based therapy. METHODS: DeLLphi-304 is a multicenter, open-label, randomized phase 3 study in adults with ES-SCLC. PROs were assessed using validated instruments, including the EORTC QLQ-C30, EORTC QLQ-LC13, FACT-G GP5, BPI-SF, and the EQ-5D-5L visual analogue scale. Change from baseline, response rates, and time to deterioration in these PROs were analyzed. RESULTS: PRO data from all 509 patients enrolled were evaluated. Compliance with QLQ-C30 and QLQ-LC13 assessments remained above 69% through 19 weeks. A higher proportion of patients receiving tarlatamab achieved symptom or functional improvement at 19 weeks compared with SoC in chest pain (19% vs 10%), cough (35% vs 26%), dyspnea (22% vs 7%), physical functioning (13% vs 8%), and global health status (23% vs 15%), respectively. Tarlatamab also delayed deterioration in symptoms, physical functioning, and pain at worst relative to SoC. FACT-G GP5 results indicated that patients receiving tarlatamab were less bothered by treatment side effects over time. CONCLUSIONS: In addition to its previously reported antitumor activity, tarlatamab demonstrated clinically meaningful improvements in symptoms and HRQoL compared with SoC. These findings support a favorable benefit-risk profile of tarlatamab in patients previously treated for ES-SCLC.

Humans↗

PubMed2007

Screening and analysis of the multiple absorbed bioactive components and metabolites of Dangguibuxue decoction by the metabolic fingerprinting technique and liquid chromatography/diode-array detection mass spectrometry.

Based on the metabolic fingerprinting technique and liquid chromatography/diode array detection mass spectrometry (LC/DAD-MS), a method for rapid screening and analysis of the multiple absorbed bioactive components and metabolites of an oral solution of Dangguibuxue decoction (ODD) in rabbit plasma after oral administration of ODD was developed. The results obtained from a comprehensive comparative analysis of the fingerprints of the ODD and its metabolic fingerprints in rabbit plasma indicated that 46 components in the ODD were absorbed into the rabbit's body. Of them, ten components were tentatively identified from their MS and UV spectra and retention behaviors by comparing the results with the reported literature. They were calycosin-7-O-beta-D-glycoside, (6aR,-11aR)-hydroxy-9,10-dimethoxypterocarpan-3-O-beta-D-glycoside, ononin, L-3-hydroxy-9,10-dimethoxypterocarpan, formononetin, (3R)-7,2'-dihydroxy-3',4'-dimethoxyisoflavan, sedanenolide, E-ligustilide, Z-ligustilide, and Z-butylidenephthalide. In addition, 21 components were only found in the metabolic fingerprints, which suggested that they might be metabolites of some components in the ODD. The findings demonstrated that the proposed method could be used to rapidly and simultaneously analyze and screen the multiple absorbed bioactive constituents and metabolites in a formula of traditional Chinese medicines (TCMs) by comparing and contrasting the chromatographic fingerprints with its metabolic fingerprints. This is very important not only for the pharmaceutical discovery process and the quality control of crude drugs, but also to explain the curative mechanism of TCMs.

Administration, Oral↗

PubMed2007

Role of Janus kinase/signal transducer and activator of transcription pathway in regulation of expression and inflammation-promoting activity of high mobility group box protein 1 in rat peritoneal macrophages.

Signal transduction mechanism in the regulation of high mobility group box protein 1 (HMGB1) has not yet been well elucidated. Our data showed for the first time that Janus kinase-signal transduction and activator of transcription (JAK/STAT) pathway played a major role in the regulation of expression and inflammatory effect of HMGB1. The study was carried out in the following sequence. Firstly, the role of JAK/STAT pathway in the regulation of expression of HMGB1 was examined. After stimulation with 75 ng/mL LPS in vitro, significant increases in HMGB1 expression and prompt activation of JAK/STAT pathway were demonstrated in cultured macrophages. On the other hand, administration of AG490 (specific inhibitor for JAK2), fludarabine (specific inhibitor for STAT1) or rapamycin (specific inhibitor for STAT3) markedly suppressed HMGB1 expression. Secondly, the role of JAK/STAT pathway in the regulation of TNF-alpha expression induced by HMGB1 was examined. When macrophages were stimulated with 10 microg/mL HMGB1 in vitro, significant increases in TNF-alpha expression and prompt activation of JAK/STAT pathway were demonstrated, whereas inhibitors of JAK/STAT pathway significantly suppressed TNF-alpha expression. Taken together, our data strongly indicated that expression and inflammatory effect of HMGB1 could be mediated by JAK/STAT pathway and suggested a possible clinical strategy to control an inflammatory effect of HMGB1 in sepsis.

Animals↗

PubMed2006

Quantitative determination of amantadine in human plasma by liquid chromatography-mass spectrometry and the application in a bioequivalence study.

A sensitive liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS) method is developed and validated for rapid determination of amantadine in human plasma. Desloratadine was used as the internal standard (I.S.). Human plasma (0.2 mL) was first alkalified with 100 microL of sodium hydroxide (3M) and then extracted with 1 mL of n-hexane containing 1% isopropanol (v/v) and 10% dichloromethane (v/v) by vortex-mixer for 3 min. The mixture was centrifuged at 14,000 rpm for 5 min. The supernatant was evaporated to dryness and the residue was dissolved in mobile phase. Samples were separated using a Thermo Hypersil-HyPURITYC18 reversed-phase column (150 mm x 2.1 mm i.d., 5 microm). Mobile phase consisted of methanol-acetonitrile-20 mM ammonium acetate (45:10:45, v/v/v) containing 1% acetic acid with pH 4.0. Amantadine and I.S. were measured by electrospray ion source in positive selective ion monitoring mode. The good linearity ranged from 3.9 to 1000 ng/mL and the lowest limit of quantification was 3.9 ng/mL. The extraction efficiencies were approximately 70% and recoveries of method ranged from 98.53 to 103.24%. The intra-day relative standard deviations (R.S.D.) were less than 8.43% and inter-day R.S.D. below 10.59%. The quality control samples were stable when kept at room temperature for 12h, at -20 degrees C for 30 days and after four freeze/thaw cycles. The method has been successfully used to evaluation of the pharmacokinetics and bioequivalence of amantadine in 20 healthy volunteers after an oral dose of 100 mg amantadine.

Amantadine↗

PubMed2006

Size-controllable fabrication of noble metal nanonets using a TiO2 template.

We present herein a simple template method for preparing noble metal nanonets with defined sizes. The template utilized is a TiO2 nanotube (NT) array prepared by anodic oxidation of a pure titanium sheet in an electrolyte solution containing sodium fluoride. Uniform NTs with defined sizes are obtained by controlling the anodic potential. Gold nanonets are prepared by electrodepositing gold onto the template and then dissolving the TiO2 template in a 0.2 M HF solution. The pore size of the gold nanonet is determined by the TiO2 NT hole size. The formation mechanism of the nanonet is elucidated from field-emission scanning electron microscopy and transmission electron microscopy. Although a lot of reports have been presented on the synthesis of nanostructure materials, no work has been reported on the template synthesis of gold nanonets. This paper gives a simple and universal way to prepare noble metal nanonets.

Chemistry, Inorganic↗

PubMed2006

Molecular authentication of the traditional Chinese medicinal plant Euphorbia pekinensis.

The ITS regions of Euphorbia pekinensis and six other Euphorbia species used as adulterants of E. pekinensis were sequenced to differentiate them. The sequences are identical among the individuals in the seven species studies. Diversity in DNA sequences among various species was found ranging from 8.3% to 43.8% in ITS1 and 7.6% to 36.6% in ITS2 region. Furthermore, based on the divergent ITS regions, species-specific primers, JDJp 1 and JDJp 2, were designed in the polymorphic regions of E. pekinensis to distinguish it from adulterants. These ITS-derived primers amplified a 281-bp-specific DNA fragment from E. pekinensis. No amplified product was observed using DNA of six adulterants.

Amino Acid Sequence↗

PubMed2006

Simultaneous tether extraction contributes to neutrophil rolling stabilization: a model study.

Neutrophil rolling is the initial step of neutrophil recruitment to sites of inflammation. During the rolling, membrane tethers are very likely extracted from both the neutrophil and the endothelial cell lining of vessel walls. Here, we present a two-dimensional neutrophil-rolling model to investigate whether and how membrane tethers contribute to stable neutrophil rolling. In our model, neutrophils are assumed to be rigid spheres covered with randomly distributed deformable microvilli, and endothelial cells are modeled as flat membrane surfaces decorated with evenly distributed ligands. The instantaneous rolling velocity and other unknowns of the model are calculated by coupling the hydrodynamic resistance functions, the geometric relationships, and the constitutive equations that govern microvillus extension and tether extraction. Our results show that glutaraldehyde-fixed neutrophils (without microvillus extension or tether extraction) roll unstably on a P-selectin-coated substrate with large variance in rolling velocity. In contrast, normal neutrophils roll much more stably, with small variance in rolling velocity. Compared with tether extraction from the neutrophil alone, simultaneous tether extraction from the neutrophil and endothelial cell greatly increases the lifetime of the adhesive bond that mediates the rolling, allows more transient tethers to make the transition into stable rolling, and enables rolling neutrophils to be more shear-resistant.

Cell Adhesion↗

PubMed2006

Identification of nuclear import mechanisms for the neuronal Cdk5 activator.

The activation of Cdk5 by p35 plays a pivotal role in a multitude of nervous system activities ranging from neuronal differentiation to degeneration. A fraction of Cdk5 and p35 localizes in the nucleus where Cdk5-p35 exerts its functions via protein phosphorylation, and p35 displays a dynamic localization between the cytoplasm and the nucleus. Here, we examined the nuclear import properties of p35. In nuclear import assays, p35 was actively transported into the nuclei of digitonin-permeabilized HeLa cells and cortical neurons by cytoplasmic carrier-mediated mechanisms. Importin-beta, importin-5, and importin-7 were identified to import p35 into the nuclei via a direct interaction with it. An N-terminal region of p35 was defined to interact with the above importins, serving as a nuclear localization signal. Finally, we show that the nuclear localization of p35 does not require the association of Cdk5. Furthermore, Cdk5 and importin-beta/5/7 are mutually exclusive in binding to p35. These results suggest that p35 employs pathways distinct from that used by Cdk5 for transport to the nucleus.

Active Transport, Cell Nucleus↗

PubMed2006

Genome sequence alterations detected upon passage of Burkholderia mallei ATCC 23344 in culture and in mammalian hosts.

BACKGROUND: More than 12,000 simple sequence repeats (SSRs) have been identified in the genome of Burkholderia mallei ATCC 23344. As a demonstrated mechanism of phase variation in other pathogenic bacteria, these may function as mutable loci leading to altered protein expression or structure variation. To determine if such alterations are occurring in vivo, the genomes of various single-colony passaged B. mallei ATCC 23344 isolates, one from each source, were sequenced from culture, a mouse, a horse, and two isolates from a single human patient, and the sequence compared to the published B. mallei ATCC 23344 genome sequence. RESULTS: Forty-nine insertions and deletions (indels) were detected at SSRs in the five passaged strains, a majority of which (67.3%) were located within noncoding areas, suggesting that such regions are more tolerant of sequence alterations. Expression profiling of the two human passaged isolates compared to the strain before passage revealed alterations in the mRNA levels of multiple genes when grown in culture. CONCLUSION: These data support the notion that genome variability upon passage is a feature of B. mallei ATCC23344, and that within a host B. mallei generates a diverse population of clones that accumulate genome sequence variation at SSR and other loci.

Animals↗

PubMed2006

Nanoparticle-assisted surface immobilization of phospholipid liposomes.

Phospholipid liposomes (100-200 nm diameter) are deposited onto solid substrates after stabilizing them against fusion with the solid by allowing charged nanoparticles to adsorb at approximately 25% surface coverage. The immobilized vesicles remain stable over a period of days. Epifluorescence imaging shows that they diffuse freely over surfaces with the same charge but adsorb tightly onto surfaces with opposite charge. Nanoparticle adsorption to surface patterns of opposite charge provides a facile method to create large-scale surface-supported arrays of intact liposomes. This surface attachment method is simple chemically and applies generally for solid surfaces that can be hydrophobic or hydrophilic. Offering routes to localize proteins and other vesicle-contained objects at surfaces in tailored spatial patterns, these immobilized liposome arrays may find diverse applications in the emerging field of nanobiotechnology.

Adsorption↗

PubMed2006

[The influence of CD14 genomic polymorphism on CD14 gene expression as well as protein release and its clinical significance in patients with extensive burns].

OBJECTIVE: To investigate the influence of a lipopolysaccharide receptor CD14-159C/T genomic polymorphism on CD14 gene expression as well as protein release, and the relation of sepsis susceptibility and prognosis in patients with extensive burns. METHODS: The study group consisted of 26 patients with burns covering more than 30% of the total body surface area. The CD14 gene polymorphism was determined by polymerase chain reaction (PCR) and subsequent HaeIII restriction enzyme digestion of the PCR products. Meanwhile, the association of CD14, TNF-alpha mRNA expression in leukocytes and soluble CD14 (sCD14) levels in serum with CD14-159 polymorphism as well as prognosis after burns was also studied. RESULTS: The T allele frequencies in sepsis patients and non-survivors were higher than those in non-septic patients and survivors. The levels of CD14 mRNA, TNF-alpha mRNA expression and serum sCD14 were significantly different among patient groups with TT, TC, and CC genotypes. The above differences were also existed between survivors and non-survivors. CD14 mRNA expression was higher in heterozygotes (TT and TC) than in C homozygous patients (P < 0.05 or P < 0.01), and sCD14 level was higher in heterozygotes (TC) than C homozygous patients on day 7 postburn (P < 0.05). During the 28-day observation period, mean TNF-alpha mRNA expression was higher in patients homozygous for T allele than C homozygotes (P < 0.05). In addition, higher CD14 mRNA values were found in non-survivors compared to those in survivors on days 7 and 28 postburn (P < 0.05). CONCLUSIONS: CD14C-159T polymorphism might markedly influence CD14 mRNA expression and sCD14 levels, and it seems to be associated with sepsis susceptibility and prognosis in patients with extensive burns. The T allele could be a genetic risk marker of adverse prognosis.

Adult↗

PubMed2006

[The potential mechanism on signal transduction pathway in regulation of mRNA expression of high mobility group box-1 protein in septic rats].

OBJECTIVE: To investigate the potential role of Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway in regulation of gene expression of high mobility group box-1 protein (HMGB1) in various tissues in rats with sepsis. METHODS: A sepsis model reproduced by cecal ligation and puncture (CLP), and 128 male Wistar rats were randomly divided into normal control group (n = 10), sham operation group (n = 10), CLP group (n = 60), AG490 treatment group (n = 24), and rapamycin (RPM) treatment group (n = 24). At serial time points animals in each group were sacrificed after CLP, then tissue samples were harvested to determine HMGB1 mRNA expression and STAT1/3 DNA binding activity. RESULTS: STAT1 activities increased rapidly in the liver, lungs and small intestine after CLP, peaking at 6 - 12 h, while it increased slowly, and still kept at mild level from 2 to 48 h in the kidneys. Compared with STAT1, lower STAT3 activities were detected only in the liver and lungs, with negative detection in the small intestine and kidneys. HMGB1 mRNA levels significantly increased in liver, lungs and small intestine at various time points after CLP respectively (P < 0.05 or P < 0.01), while they didn't change in the kidneys. Treatment with AG490 could markedly inhibit HMGB1 mRNA expression in the liver and small intestine at 24 and 48 h (P < 0.05 or P < 0.01), and in lungs at 2 h following CLP (P < 0.01). Similarly, treatment with RPM significantly decreased HMGB1 mRNA expression in the lungs at 2, 6, 24 and 48 h, in the liver at 6 and 24 h, and in the small intestine at 24 and 48 h (P < 0.05 or P < 0.01). In addition, STAT1 and STAT3 activities in the liver and lungs were significantly correlated with corresponding tissue HMGB1 mRNA expression. CONCLUSIONS: Peritoneal infection could extensively activate STAT1 and limitedly activate STAT3 in vital organs. Activation of JAK/STAT pathway might be involved in up-regulating the gene expression of HMGB1 and systemic inflammation secondary to severe septic challenge.

Animals↗

PubMed2006

Ligustilide inhibits spontaneous and agonists- or K+ depolarization-induced contraction of rat uterus.

In the present study, the effects of ligustilide (LIG) on uterine contraction in vitro were investigated. In isolated rat uterine, LIG (2-8 microg/ml) inhibited the spontaneous periodic contraction in a concentration-dependent manner (EC(50)=4.4 microg/ml, 95% confidence interval 2.7-6.1 microg/ml), and attenuated prostaglandin F2alpha (PGF(2)alpha)- or acetylcholine chloride (Ach)-induced uterine contractions. At 8 microg/ml, LIG nearly completely blocked the PGF(2)alpha-induced contractions (95.3%). In the case of Ach-induced contraction, about 73.9% was inhibited by LIG at this dosage. It was also observed that LIG affected significantly oxytocin-induced increase in the contraction of uterine horns that were incubated not only in the Locke solution but also in a Ca(2+)-free solution. In addition, LIG caused concentration-dependent inhibition of uterine contraction induced by K(+) (56.3 Mm) depolarization, reaching the significant level at 2 microg/ml (EC(50)=3.3 microg/ml, 95% confidence interval 2.5-4.1 microg/ml). The findings clearly show that LIG has multiple effects on the uterine smooth muscles, suggesting that LIG possesses a non-specific antispasmodic function. The data also imply strongly that LIG is one of active ingredients of Danggui and has the potential to be developed into an effective drug for the prevention and treatment of primary dysmenorrhoea.

4-Butyrolactone↗

PubMed2006

[Effect of inhibitors of signal transducer and activator of transcription-1/3 on expression of tumor necrosis factor-alpha induced by high mobility group box-1 protein inflammatory response in rat peritoneal macrophages].

OBJECTIVE: To investigate the inflammatory signal transduction of high mobility group box-1 protein (HMGB1) induced inflammatory response in rat peritoneal macrophages. METHODS: Peritoneal macrophages obtained from male Wistar rats were seeded in 24-well (1 x 10(6) cells/well) tissue culture plates. The cells were incubated for 3 days before they were stimulated with HMGB1, and treated with Fludarabine [the specific inhibitor of signal transducer and activator of transcription 1 (STAT1)] or Rapamycin (the specific inhibitor of STAT3). The time-dependent and dose-dependent responses between HMGB1 stimulation and tumor necrosis factor-alpha (TNF-alpha) gene expression as well as release were analyzed respectively. Moreover, the effect of Fludarabine and Rapamycin on TNF-alpha mRNA expression and protein release were also observed. RESULTS: (1) After HMGB1 challenge, TNF-alpha mRNA expressions were up-regulated markedly, peaked at 24 hours, and decreased at 36 hours. When HMGB1 was used at a concentration of 10 microg/ml, TNF-alpha mRNA expression increased most markedly. (2) HMGB1 could induce TNF-alpha release in rat peritoneal macrophages, with peaking at 4 hours and decreasing at 8 hours later. When the concentration of HMGB1 stimulation increased from 5 microg/ml to 25 microg/ml, TNF-alpha release was persistently enhanced. (3) It was also showed that TNF-alpha mRNA expression was significantly inhibited by treatment of either Fludarabine (100 micromol/L) or Rapamycin (25 ng/ml), while TNF-alpha release was not markedly suppressed. CONCLUSIONS: STAT1 and STAT3 might be involved in the regulation of TNF-alpha gene expression, but not in TNF-alpha early release (< 24 hours) induced by HMGB1 stimulation in rat peritoneal macrophages.

Animals↗

PubMed2006

Image-guided brachytherapy for prostate cancer.

Prostate brachytherapy offers and effective treatment for organ-confined prostate carcinoma. It is rapidly delivered compared with external beam radiation therapy or surgery and well tolerated by patients. Volumetric imaging and image guidance play critical roles in patient selection, treatment planning, treatment delivery, and postimplant assessment. Costs, availability and ease of use often dictate the local and regional differences in imaging approach, whether ultrasound, CT, or MR. Future volumetric image developments may permit multimodality image fusion to integrate tumor-specific imaging such as MR spectroscopy or positron emission tomography/CT into real-time ultrasound, CT, or MR.

Brachytherapy↗

PubMed2006

Local signals in stem cell-based bone marrow regeneration.

The cellular basis of bone marrow (BM) tissue development and regeneration is mediated through hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs). Local interplays between hematopoietic cells and BM stromal cells (BMSCs) determine the reconstitution of hematopoiesis after myelosuppression. Here we review the BM local signals in control of BM regeneration after insults. Hematopoietic growth factors (HGFs) and cytokines produced by BMSCs are primary factors in regulation of BM hematopoiesis. Morphogens which are critical to early embryo development in multiple species have been added to the family of HSCs regulators, including families of Wnt proteins, Notch ligands, BMPs, and Hedgehogs. Global gene expression analysis of HSCs and BMSCs has begun to reveal signature groups of genes for both cell types. More importantly, analysis of global gene expression coupled with biochemical and biological studies of local signals during BM regeneration have strongly suggested that HGFs and cytokines may not be the primary local regulators for BM recovery, rather chemokines (SDF-1, FGF-4) and angiogenic growth factors (VEGF-A, Ang-1) play instructive roles in BM reconstitution after myelosuppression. A new direction of management of BM toxicity is emerging from the identification of BM regenerative regulators.

Bone Marrow Cells↗

PubMed2006

Hybrid dosimetry: feasibility of mixing angulated and parallel needles in planning prostate brachytherapy.

Pubic arch interference (PAI) often caused inadequate prostate coverage during transperineal brachytherapy using all parallel needles. In this paper, a hybrid implantation approach is presented in which additional angulated needles can be used to avoid PAI. This approach can be applied in prostate brachytherapy using a robotic assisted device. To examine the feasibility of this approach, volume data from three prostate seed implant patients were selected, which represent small, medium, and large prostates. As the blocking area was artificially increased simulating pubic arch overlap, the dosimetry outcomes and ratio of number of angulated needles to the total number of needles were analyzed. The hybrid dosimetry broke down when blocking is over 42%. As the percent of blocking increased, the ratio of the number of angulated needles to the total number of needles increased, while the dosimetry outcomes only had a slight trend of worsening. When close to the breakdown point, the dosimetry outcomes worsen drastically. Therefore, for moderate PAI the hybrid dosimetry is feasible.

Brachytherapy↗