Biomedical subjects

Nan Yang

Publications and source records attributed to Nan Yang.

17 recordsLinked to original sources

PubMed2026

Day + 30 detection of minimal residual FLT3-ITD by high-sensitivity PCR-NGS predicts relapse risk and guides post-transplant maintenance in AML.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has improved outcomes in patients with acute myeloid leukemia (AML) harboring FLT3-internal tandem duplication (FLT3-ITD) mutations. However, relapse still occurs in 15-35% of these patients after transplantation. Therefore, early and highly sensitive detection methods are required to identify patients at risk of relapse and enable timely post-transplant intervention. METHODS: In this NICHE cohort study, a total of 136 patients were included, then we evaluated whether high-sensitivity polymerase chain reaction (PCR)-next-generation sequencing (NGS) for FLT3-ITD (limit of detection: 5 × 10-6) on day + 30 post-HSCT could identify patients at a high risk of relapse and inform decisions regarding maintenance therapy. RESULTS: Among the 136 patients, 37 patients (27.2%) had detectable FLT3-ITD clones on day + 30. These patients exhibited a significantly higher cumulative incidence of post-HSCT multiparameter flow cytometry (MFC)-measurable residual disease (MRD) relapse (40.3% vs. 18.8%, p = 0.001). Notably, FLT3-ITD-positive patients who received FLT3 inhibitor maintenance therapy had no relapses, while 6 out of the 13 patients who did not receive maintenance therapy relapsed. Conversely, FLT3-ITD-negative patients without high-risk factors (2022 European LeukemiaNet adverse-risk group, relapsed/refractory AML, MFC-MRD positivity pre-HSCT) showed limited benefit from maintenance therapy (MFC-MRD-free survival: hazard ratio (HR) = 0.25 (0.03-2.11), p = 0.204; OS: HR = 0.20 (0.02-1.70), p = 0.142). CONCLUSIONS: This is the first study to demonstrate that detection of minimal FLT3-ITD clones at the fixed time point of day + 30 post-HSCT can reliably stratify relapse risk in AML patients and provide a rationale for individualized post-transplant maintenance therapy.

Humans↗

PubMed2026

Deciphering the Protein Phosphorylation Dynamics Triggered by Seconds of Force Stimulation.

Plants perceive mechanical forces through phosphosignaling networks, but their relationship with gravity signaling remains elusive. To dissect gravity force signaling components, we performed SILIA-based phosphoproteomics on Arabidopsis aerial organs subjected to 20-s inversion or 30-s gravistimulation, identifying 2,733 and 2,878 phosphoproteins, respectively. Quantitative analysis revealed 34 significantly regulated phosphoproteins specific to inversion and 52 specific to gravistimulation. Inversion-specific phosphoproteins, associated with the initial calcium code, likely mediate calcium signals through EF-hand proteins, CPK1, and calmodulin-interacting proteins, potentially intersecting with receptor-like kinase-initiated MAPK cascades via RAF15 and MKK1/2 to induce gravitropic responses. Gravistimulation-specific phosphoproteins, linked to the secondary calcium code, function in calcium signaling/homeostasis (ACA8, ZAC, IQD2, ANNAT1), membrane vesicle trafficking (ABCG36, ARF-GAP8), and lipid signaling (PIP5K8/9), supporting auxin transport and stress signal transduction. Immunoblot validation confirmed treatment-associated phosphosites pS108-PATL3 and pS107-TREPH2, along with inversion-specific pS1145-ATEH2, exhibiting stem-specific phosphorylation enhancement and force-discriminatory responses. Functional analysis identified the integrin-like protein GREPH1 as a key gravitropism regulator, with greph1 mutants displaying reduced inflorescence stem gravicurvature. Notably, hyperphosphorylation of pS107-TREPH2 and pS1145-ATEH2 peaked at 20 to 50 s in greph1 mutants but persisted from 20 s to 2 h in WT plants. These findings establish a stem-enriched phosphorylation code for gravity force discrimination, with GREPH1 modulating spatiotemporal phosphoprotein dynamics and shoot gravicurvature, potentially functioning as a receptor reminiscent of sedimenting plastids.

Arabidopsis↗

PubMed2007

Evaluation of two- and three-dimensional streptavidin binding platforms for surface plasmon resonance spectroscopy studies of DNA hybridization and protein-DNA binding.

Surface plasmon resonance (SPR) spectroscopy has been used to study DNA assembly, DNA hybridization, and protein-DNA interactions on two streptavidin (SA) sensor chips. On one chip, SA molecules are immobilized on a biotin-exposed surface, forming an ordered two-dimensional (2D) SA monolayer. The other chip, BIAcore's SA chip, contains SA molecules immobilized within a three-dimensional (3D) carboxylated dextran matrix. Compared to the 2D chip, the 3D SA matrix allows for a slower immobilization rate of biotinylated DNA due to diffusion limitation in the dextran matrix, but with twice the amount of the immobilized DNA due to the greater number of reactive sites, which in turn enables a higher sensitivity for DNA hybridization detection. Interestingly, having a greater DNA probe dispersion in the 3D matrix does not induce a higher DNA hybridization efficiency. In a study of protein binding to immobilized DNA (estrogen receptor to estrogen response elements), aiming at assessing the DNA sequence dependent protein binding behavior, the 2D and 3D chips produce different binding characteristics. On the 2D chip, the protein binding exhibits a better selectivity to the specific sequences, regardless of binding stringency (e.g. salt concentration), whereas on the 3D chip, the liquid handling system needs to be optimized in order to minimize transport limitations and to detect small affinity differences. Through this study we demonstrate that the physicochemical structure of SPR chips affects the apparent binding behaviors of biomolecules. When interpreting SPR binding curves and selecting a sensor chip, these effects should be taken into account.

Biosensing Techniques↗

PubMed2006

A subunit of the mediator complex regulates vertebrate neuronal development.

The unique profiles of gene expression dictate distinct cellular identity. How these profiles are established during development is not clear. Here we report that the mutant motionless (mot), identified in a genetic screen for mutations that affect neuronal development in zebrafish, displays deficits of monoaminergic neurons and cranial sensory ganglia, whereas expression of the pan-neuronal marker Hu is largely unperturbed; GABAergic and subsets of cranial motor neurons do not appear to be deficient. Positional cloning reveals that mot encodes Med12, a component of the evolutionarily conserved Mediator complex, whose in vivo function is not well understood in vertebrates. mot/med12 transcripts are enriched in the embryonic brain and appear distinct from two other Mediator components Med17 and Med21. Delivery of human med12 RNA into zebrafish restores normality to the mot mutant and, strikingly, leads to premature neuronal differentiation and an increased production of monoaminergic neuronal subtypes in WT. Further investigation reveals that mot/med12 is necessary to regulate, and when overexpressed is capable of increasing, the expression of distinct neuronal determination genes, including zash1a and lim1, and serves as an in vivo cofactor for Sox9 in this process. Together, our analyses reveal a regulatory role of Mot/Med12 in vertebrate neuronal development.

Animals↗

PubMed2006

Association analysis of the ACTN3 R577X polymorphism and complex quantitative body composition and performance phenotypes in adolescent Greeks.

The functional allele (577R) of ACTN3, which encodes human alpha-actinin-3, has been reported to be associated with elite athletic status and with response to resistance training, while the nonfunctional allele (577X) has been proposed as a candidate metabolically thrifty allele. In a study of 992 adolescent Greeks, we show that there is a significant association (P=0.003) between the ACTN3 R577X polymorphism and 40 m sprint time in males that accounts for 2.3% of phenotypic variance, with the 577R allele contributing to faster times in an additive manner. The R577X polymorphism is not associated with other power phenotypes related to 40 m sprint, nor with an endurance phenotype. Furthermore, the polymorphism is not associated with obesity-related phenotypes in our population, suggesting that the 577X allele is not a thrifty allele, and thus the persistence of this null allele must be explained in other terms.

Actinin↗

PubMed2006

[Correlation of changes of peripheral benzodiazepine receptors in hippocampus synaptosomes with cognitive impairment: experiment with D-galactose-induced senescent rats].

OBJECTIVE: To investigate the effects of peripheral benzodiazepine receptor (PBR) in hippocampus synaptosomes on spatial learning and memory. METHODS: Twenty-four Sprague-Dawley rats of both sexes were randomly divided into 2 equal groups: D-galactose-treated group, receiving subcutaneous injection of D-galactose 100 mg/kg once a day for 56 days, and normal saline (NS) control group, receiving comparable injections of NS. Spatial learning and memory were assessed by Morris water maze test for 5 days. After the behavioral testing all rats were decapitated and the hippocampus was removed immediately. Then, the synaptosomes in hippocampus were purified by density gradient centrifugation. The PBR binding parameters, maximal binding site density (B(max)) and equilibrium dissociation constant (KD), were estimated by radioligand [(3)H] PK11195 binding assays. RESULTS: Two weeks after the beginning of experiment the D-galactose-treated rats began to show symptoms of aging. On the 5th day of behavioral testing the D-galactose-induced aging rats presented significant impairment in water maze performance compared with the NS controls (P < 0.001). The decrease in specific [(3)H] PK11195 binding in the hippocampus synaptosomes of the D-galactose-treated group was 67.3 +/- 18.6 fmol/mg, significantly lower than that of the saline control group (127.9 +/- 20.1 fmol/mg, P < 0.01). The Scatchard analysis revealed that the B(max) of the D-galactose-treated group was 177.2 +/- 26.7 fmol/mg, significantly lower than that of the saline group (296.7 +/- 33.5 fmol/mg, P < 0.01), and the K(D) of the D-galactose-treated group was 0.503 +/- 0.06 nmol/L, not significantly different from that of the saline control group (0.502 +/- 0.05 nmol/L). Correlation analysis showed that the specific [(3)H] PK11195 binding in hippocampus synaptosomes was closely related to the escaping latency (r = -0.854), swimming time (r = 0.845), and distance (r = 0.851) in platform quadrant in Morris water maze in all rats (all P < 0.001). CONCLUSION: The decreased expression of PBR in hippocampus synaptosomes is possibly associated with the spatial learning-memory impairments induced by D-galactose.

Aging↗

PubMed2005

Examination of ancestry and ethnic affiliation using highly informative diallelic DNA markers: application to diverse and admixed populations and implications for clinical epidemiology and forensic medicine.

We and others have identified several hundred ancestry informative markers (AIMs) with large allele frequency differences between different major ancestral groups. For this study, a panel of 199 widely distributed AIMs was used to examine a diverse set of 796 DNA samples including self-identified European Americans, West Africans, East Asians, Amerindians, African Americans, Mexicans, Mexican Americans, Puerto Ricans and South Asians. Analysis using a Bayesian clustering algorithm (STRUCTURE) showed grouping of individuals with similar ethnic identity without any identifier other than the AIMs genotyping and showed admixture proportions that clearly distinguished different individuals of mixed ancestry. Additional analyses showed that, for the majority of samples, the predicted ethnic identity corresponded with the self-identified ethnicity at high probability (P > 0.99). Overall, the study demonstrates that AIMs can provide a useful adjunct to forensic medicine, pharmacogenomics and disease studies in which major ancestry or ethnic affiliation might be linked to specific outcomes.

Algorithms↗

PubMed2005

The syntrophin-dystrobrevin subcomplex in human neuromuscular disorders.

The syntrophins and alpha-dystrobrevin form a subcomplex with dystrophin at the skeletal muscle membrane, and are also highly concentrated at the neuromuscular synapse. Here we demonstrate that the different syntrophins and alpha-dystrobrevin isoforms have distinct expression patterns during human skeletal muscle development, and are differentially affected by loss of dystrophin anchorage and denervation in human neuromuscular disease. During normal fetal development, and in Duchenne muscular dystrophy and denervation disorders, alpha1-syntrophin and alpha-dystrobrevin are absent or markedly reduced at the sarcolemmal membrane. beta1-Syntrophin is the predominant syntrophin isoform expressed at the muscle membrane during development, and it undergoes upregulation in response to loss of alpha1-syntrophin in Duchenne muscular dystrophy and in denervation. Upregulation of beta1-syntrophin in neuromuscular disorders is associated with re-expression of the fetal nicotinic acetylcholine receptor gamma-subunit, cardiac actin, and neonatal myosin, suggesting reversion of muscle fibers to an immature phenotype. We show that denervation specifically affects expression of the syntrophin-dystrobrevin subcomplex and does not affect levels or localization of other members of the dystrophin-associated protein complex. Our results confirm that dystrophin is required for anchorage of the syntrophin-dystrobrevin subcomplex and suggest that expression of the syntrophin-dystrobrevin complex may be independently regulated through neuromuscular transmission.

Animals↗

PubMed2005

Gene expression profile of amyloid beta protein-injected mouse model for Alzheimer disease.

AIM: To investigate the gene expression profile changes in the cerebral cortex of mice injected icv with amyloid beta-protein (Abeta) fragment 25-35 using cDNA microarray. METHODS: Balb/c mice were randomly divided into a control group and Abeta-treated group. The Morris water maze test was performed to detect the effect of Abeta-injection on the learning and memory of mice. Atlas Mouse 1.2 Expression Arrays containing 1176 genes were used to investigate the gene expression pattern of each group. RESULTS: The gene expression profiles showed that 19 genes including TBX1, NF-kB, AP-1/c-Jun, cadherin, integrin, erb-B2, and FGFR1 were up-regulated after 2 weeks of icv administration of Abeta; while 12 genes were down-regulated, including NGF, glucose phosphate isomerase 1, AT motif binding factor 1, Na+/K+-ATPase, and Akt. CONCLUSIONS: The results provide important leads for pursuing a more complete understanding of the molecular events of Abeta-injection into mice with Alzheimer disease.

Alzheimer Disease↗

PubMed2005

Tissue-specific tropomyosin isoform composition.

Four distinct genes encode tropomyosin (Tm) proteins, integral components of the actin microfilament system. In non-muscle cells, over 40 Tm isoforms are derived using alternative splicing. Distinct populations of actin filaments characterized by the composition of these Tm isoforms are found differentially sorted within cells (Gunning et al. 1998b). We hypothesized that these distinct intracellular compartments defined by the association of Tm isoforms may allow for independent regulation of microfilament function. Consequently, to understand the molecular mechanisms that give rise to these different microfilaments and their regulation, a cohort of fully characterized isoform-specific Tm antibodies was required. The characterization protocol initially involved testing the specificity of the antibodies on bacterially produced Tm proteins. We then confirmed that these Tm antibodies can be used to probe the expression and subcellular localization of different Tm isoforms by Western blot analysis, immunofluorescence staining of cells in culture, and immunohistochemistry of paraffin wax-embedded mouse tissues. These Tm antibodies, therefore, have the capacity to monitor specific actin filament populations in a range of experimental systems.

Actins↗

PubMed2005

[Effects of acidic oligose on differentially expressed genes in the mice model of Alzheimer's disease by microarray].

AIM: To investigate the molecular mechanism of protective effect of acidic oligose 971 on Alzheimer's disease mouse model by using microarray. METHODS: Balb/c mice were randomly divided into control group, beta-AP(25-35) i.c.v. injected group and 971-treated group. The learning-memory ability of mice was tested by Morris water maze experiment. Total RNA of the cerebral cortex was extracted from the mice of each group. cDNA microarrays containing 1176 genes were used to investigate the gene expression pattern of each group. Expressions of 5 genes were randomly selected for further confirmation by RT-PCR. RESULTS: Icv injection of beta-AP(25-35) caused significant impairments in spatial and working memory performances of mice in Morris water maze and which were relieved by the treatment of 971. Up- and down- regulated genes were 19 and 12 in beta-AP(25-35)-injected group vs control group, respectively. Up- and down- regulated genes were 13 and 4, respectively, in 971-treated group vs beta-AP(25-35)-injected group. RT-PCR results indicated that 5 genes showed identical results to that of the microarray. CONCLUSION: The protective effect of 971 on learning and memory ability of beta-AP(25-35)-treated mouse may be related to the expression changes of genes involved in cell cycle, DNA repair, nerve growth, synaptic plasticity and immune response, etc.

Alzheimer Disease↗

PubMed2004

Expression of aquaporin 1 in human cardiac and skeletal muscle.

Aquaporins (AQPs) are a family of water channel proteins that assist in maintenance of the cellular osmotic environment and whole body fluid balance. Specialized organ-specific AQPs are important in physiologic and pathologic processes but little is known about AQPs in the human heart. AQP1 has been identified in rodent heart. We investigated the presence and localization of AQP1 in human heart and skeletal muscle using immunohistochemistry and confocal microscopy, western blot and reverse transcriptase-polymerase chain reaction. There was abundant AQP1 present in both cardiac and skeletal muscle. Immunohistochemistry revealed co-localization of AQP1 with vinculin, a t-tubule marker, and caveolin-3. No novel sequences bearing an NPA box motif common to other AQPs were identified in human heart using degenerative PCR analysis. We conclude that AQP1 is present in the human heart. AQP1 co-localizes with t-tubular and caveolar proteins. Cardiac AQPs may have a role during osmotic stresses including ischemia/reperfusion and cardiopulmonary bypass.

Adult↗

PubMed2004

[Studies on the changes in the interleukin-13 expression and on activator protein-1 activity in rat pulmonary tissue with acute lung injury induced by endotoxin].

OBJECTIVE: To investigate the changes in plasma level of interleukin-13 (IL-13) and the changes in the pulmonary IL-13 mRNA content and the pulmonary activator protein-1 (AP-1) activity of the rats inflicted with acute lung injury (ALI) induced by lipopolysaccharide (LPS), so as to explore the relationship between IL-13 expression and AP-1 activity. METHODS: One hundred and twenty Wistar rats were employed in the study and were randomly divided into A (2 mg/kg), B (4 mg/kg), C (6 mg/kg) and D (8 mg/kg) groups according to different dosage of LPS administration and a control group (NS group) at each observing time point. The rats were observed at 1, 2, 4 and 6 postburn hours (PBHs) and every 6 rats were deployed in every group and each time points. A model of systemic inflammatory response syndrome-acute lung injury (SIRS-ALI) was replicated in Wistar rats. The plasma content of IL-13 was assayed by enzyme-linked immunosorbent assay (ELISA), and the pulmonary tissue content of IL-13 mRNA and AP-1 activity by reverse transcriptase-polymerase chain reaction (RT-PCR) and electrophoretic mobility shift assays (EMSA). RESULTS: The plasma content of IL-13, pulmonary content of IL-13 mRNA and AP-1 activity increased simultaneously after LPS administration. All the above indices were significantly different statistically between the LPS groups and the control group (P < 0.05 - 0.01). The plasma level of IL-13 and pulmonary tissue mRNA content and AP-1 activity in A, B, C and D groups were increased significantly with peak levels at 2 PBHs. CONCLUSION: The pulmonary AP-1 activity increased with the enhanced expression of IL-13, which was related to the development of SIRS-ALI.

Acute Lung Injury↗

PubMed2004

[Effect of Tujian decoction on protein kinase C activity in renal cortex in diabetic rat].

OBJECTIVE: To investigate influence of administration of Tujian decoction (Chinese herbal medicine) on protein kinase C (PKC) activity, renal function and structure in diabetic rat kidney. METHOD: Experimental diabetic nephropathy model was induced by nephrectomy combined with streptozotocin (STZ) injection in sprague-dawley rat. Tujian decoction (20 g x kg(-1) x d(-1)) and Valsartan (20 mg x kg(-1) x d(-1)) were orally administrated respectively for 12 weeks. PKC activity was measured by [3H]phorbol 12, 13-dibutyrate ([3H]PDBu) binding assay. 24 h urine protein excretion (Upro) and renal pathological changes were observed. RESULT: In 12th week, diabetic nephrectomized rats developed proteinuria, glomerulosclerosis, increased membrane PKC activity (mPKC), decreased cytosol PKC (cPKC), and increased ratio of mPKC and cPKC (M/C). Administration of Tujian decoction or Valsartan led to a reduction in proteinuria, structural injury, mPKC and M/C, and a recovery in cPKC. CONCLUSION: Tujian decoction possesses a renoprotective effect on diabetic nephrectomized rat, at least partially via the inhibition of PKC activation in renal cortex.

Animals↗

PubMed2003

Synthesis, characterization and DNA-binding properties of La(III) complex of chrysin.

A novel La(III) complex of chrysin (5,7-dihydroxyflavone) was synthesized and characterized by UV, IR, 1H NMR, thermogravimetry/differential thermal analysis (TG/DTA) and elementary analyses. The interactions of the La(III) complex and chrysin with calf thymus DNA were investigated by spectrophotometric methods and viscosity measurements. The intrinsic binding constants of La(III) complex and chrysin are 1.29 x 10(6) and 5.44 x 10(5) M(-1), respectively. Experimental results indicated that La(III) complex and chrysin can both bind to DNA by intercalation modes, but the binding affinity of La(III) complex is much higher than that of chrysin. Comparative antitumor activities of La(III) complex and chrysin were tested by MTT and SRB methods. The results show that at the concentration of 10 microM for chrysin and La(III) complex, the inhibitory ratios of La(III) complex against the tested tumor cells were higher than those of chrysin.

Animals↗

PubMed2003

ACTN3 genotype is associated with human elite athletic performance.

There is increasing evidence for strong genetic influences on athletic performance and for an evolutionary "trade-off" between performance traits for speed and endurance activities. We have recently demonstrated that the skeletal-muscle actin-binding protein alpha-actinin-3 is absent in 18% of healthy white individuals because of homozygosity for a common stop-codon polymorphism in the ACTN3 gene, R577X. alpha-Actinin-3 is specifically expressed in fast-twitch myofibers responsible for generating force at high velocity. The absence of a disease phenotype secondary to alpha-actinin-3 deficiency is likely due to compensation by the homologous protein, alpha-actinin-2. However, the high degree of evolutionary conservation of ACTN3 suggests function(s) independent of ACTN2. Here, we demonstrate highly significant associations between ACTN3 genotype and athletic performance. Both male and female elite sprint athletes have significantly higher frequencies of the 577R allele than do controls. This suggests that the presence of alpha-actinin-3 has a beneficial effect on the function of skeletal muscle in generating forceful contractions at high velocity, and provides an evolutionary advantage because of increased sprint performance. There is also a genotype effect in female sprint and endurance athletes, with higher than expected numbers of 577RX heterozygotes among sprint athletes and lower than expected numbers among endurance athletes. The lack of a similar effect in males suggests that the ACTN3 genotype affects athletic performance differently in males and females. The differential effects in sprint and endurance athletes suggests that the R577X polymorphism may have been maintained in the human population by balancing natural selection.

Actinin↗

PubMed2003

[Effects of 7-oxo-DHEA treatment on the immunoreactivity of BALB/c mice subjected to chronic mild stress].

AIM: To determine whether 7-oxo-dehydroepiandrosterone (7-oxo-DHEA) can reverse the hypoimmunity in BALB/c mice exposed to chronic mild stress. METHODS: A chronic mild stress animal model was established by subjecting BALB/c mice to a stressful regimen arranged in an unpredicted manner for 4 consecutive weeks. Immunological function alternations under chronic mild stress were assessed by lymphocytes proliferative response to mitogens and NK cell lysis activity test. RESULTS: The studies showed the correlation between the state of depression and abnormalities in the immune response, such as a decrease of T lymphocytes proliferative response to Con A and suppression of cytotoxic of NK cell. Meanwhile, significant decrease of T3 and T4 levels was also observed. When stressed mice were daily given 7-oxo-DHEA 15 mg.kg-1, lymphocyte proliferative response and the NK cell activity were significantly enhanced and the decreased levels of T3 and T4 were restored in the stressed mice. CONCLUSION: 7-oxo-DHEA can improve the depressive symptoms and hypoimmunity of BALB/c mice induced by chronic mild stress as its parent DHEA.

Adjuvants, Immunologic↗