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Rong Huang

Publications and source records attributed to Rong Huang.

At least 19 recordsLinked to original sources
PubMed2025

Transcriptome-wide analysis reveals potential roles of CFD and ANGPTL4 in fibroblasts regulating B cell lineage for extracellular matrix-driven clustering and novel avenues for immunotherapy in breast cancer.

BACKGROUND: The remodeling of the extracellular matrix (ECM) plays a pivotal role in tumor progression and drug resistance. However, the compositional patterns of ECM in breast cancer and their underlying biological functions remain elusive. METHODS: Transcriptome and genome data of breast cancer patients from TCGA database was downloaded. Patients were classified into different clusters by using non-negative matrix factorization (NMF) based on signatures of ECM components and regulators. Weighted Gene Co-expression Network Analysis (WGCNA) was used to identify core genes related to ECM clusters. Additional 10 independent public cohorts including Metabric, SCAN_B, GSE12276, GSE16446, GSE19615, GSE20685, GSE21653, GSE58644, GSE58812, and GSE88770 were collected to construct Training or Testing cohort, following machine learning calculating ECM correlated index (ECI) for survival analysis. Pathway enrichment and correlation analysis were used to explore the relationship among ECM clusters, ECI and TME. Single-cell transcriptome data from GSE161529 was processed for uncovering the differences among ECM clusters. RESULTS: Using NMF, we identified three ECM clusters in the TCGA database: C1 (Neuron), C2 (ECM), and C3 (Immune). Subsequently, WGCNA was employed to pinpoint cluster-specific genes and develop a prognostic model. This model demonstrated robust predictive power for breast cancer patient survival in both the Training cohort (n = 5,392, AUC = 0.861) and the Testing cohort (n = 1,344, AUC = 0.711). Upon analyzing the tumor microenvironment (TME), we discovered that fibroblasts and B cell lineage were the core cell types associated with the ECM cluster phenotypes. Single-cell RNA sequencing data further revealed that angiopoietin like 4 (ANGPTL4)+ fibroblasts were specifically linked to the C2 phenotype, while complement factor D (CFD)+ fibroblasts characterized the other ECM clusters. CellChat analysis indicated that ANGPTL4+ and CFD+ fibroblasts regulate B cell lineage via distinct signaling pathways. Additionally, analysis using the Kaplan-Meier Plotter website showed that CFD was favorable for immunotherapy response, whereas ANGPTL4 negatively impacted the outcomes of cancer patients receiving immunotherapy. CONCLUSION: We identified distinct ECM clusters in breast cancer patients, irrespective of molecular subtypes. Additionally, we constructed an effective prognostic model based on these ECM clusters and recognized ANGPTL4+ and CFD+ fibroblasts as potential biomarkers for immunotherapy in breast cancer.

Humans↗
PubMed2006

Simulation of infrared spectra for beta-hairpin peptides stabilized by an Aib-Gly turn sequence: correlation between conformational fluctuation and vibrational coupling.

Vibrational spectra of a 12-residue beta-hairpin peptide, RYVEVBGKKILQ (HBG), stabilized by an Aib-Gly turn sequence (B = Aib) were investigated theoretically using a combination of molecular dynamics (MD) and density functional theory (DFT) calculations. Selected conformations of HBG were extracted from a classical MD trajectory and used for spectral simulations. DFT calculations, based on the Cartesian coordinate spectral property transfer protocol, were carried out for peptide structures in which all residues are replaced with Ala, except for the Aib and Gly residues, but the backbone (phi, psi, omega) structure of the original configuration is retained. The simulations provide a basis for interpretation of the HBG amide I infrared spectra in terms of structural variables such as detailed secondary structure and thermal conformational fluctuation as well as vibrational coupling as indicated by spectra of 13C isotope-labeled variants. The characteristic amide I band shape of such small beta-hairpin peptides appears to arise from the structure of the short antiparallel beta-sheet strands. The role of structural parameter fluctuation in vibrational coupling is evaluated by comparison of DFT-derived amide coupling constants for selected configurations and from transition dipole coupling calculations of coupling parameters between (13)C isotopically labeled residues for a MD-derived ensemble of configurations. Calculated results were compared with the experimentally obtained spectra for several (13)C isotope-labeled peptides of this sequence.

Journal Article↗
PubMed2006

A systematic review and meta-analysis of the relationship between lipoprotein lipase Asn291Ser variant and diseases.

This systematic review attempted to summarize the associations between the Asn291Ser variant in the lipoprotein lipase (LPL) gene and dyslipidemia, the risk of type 2 diabetes mellitus (T2DM), and coronary heart disease (CHD). In addition, the relationships between the Asn291Ser variant and other metabolic diseases such as obesity and high blood pressure were also investigated in this systematic review. We systematically reviewed the literature by means of a meta-analysis. Twenty-one articles, including 19,246 white subjects, were selected for this meta-analysis. The summary standardized mean difference (SMD) of plasma triglyceride (TG) for carriers compared with noncarriers of the Asn291Ser variant was 3.23 (P < 0.00001). The summary SMD of plasma HDL-cholsterol (HDL-C) for carriers compared with noncarriers of the Asn291Ser variant was -3.42 (P < 0.0001). The summary SMD of the association of the Asn291Ser variant with plasma TG increased with increasing age and weight gain. Significant interactions between the LPL Asn291Ser variant and fasting glucose, T2DM, and CHD were seen (P = 0.02, 0.04, and 0.01, respectively). No significant interactions were seen between the LPL Asn291Ser variant and body mass index, waist-hip ratio, and blood pressure (P > 0.05). This meta-analysis indicates that the Asn291Ser variant in the LPL gene is a risk factor for dyslipidemia, characterized by hypertriglyceridemia and low HDL-C levels. And the Asn291Ser variant in the LPL gene predisposes to more severe dyslipidemia with increasing age and weight gain. Also, this meta-analysis shows that the LPL Asn291Ser variant is associated with CHD and T2DM.

Amino Acid Substitution↗
PubMed2006

Vincristine transcriptional regulation of efflux drug transporters in carcinoma cell lines.

The increased expression of drug transporters following cancer chemotherapy contributes to resistance. This may reflect transcriptional up-regulation and/or clonal selection. We quantified the expression of mRNA for ABCB1 (mdr1), ABCC1 (mrp1), ABCC2 (mrp2) and ABCC3 (mrp3) to evaluate the potential contribution of induction. ABCB1, ABCC1-3 mRNAs were quantified by real time RT-PCR and normalized to GAPDH. We used intestinal cells that express high pregnane X receptor (LS174T), low pregnane X receptor (Caco-2) and lung cells (A549) that express glucocorticoid receptor and low pregnane X receptor. Rifampin (10 microM) caused significant induction of ABCB1 (595+/-263%, p<0.05) in LS174T cells but induction was absent in Caco-2 or A549 cells. ABCC1 was not induced in any cell at 24, 48 and 72 h following rifampin treatment. In contrast, vincristine (10 nM and 100 nM), a ligand for ABCB1 and ABCC1-3 and a potential PXR/CAR ligand, induced ABCC2 and ABCC3 expression in LS174T cells at 48 h (372+/-87% and 303+/-42%, respectively, p<0.05). A similar induction of ABCC2 and ABCC3 genes was also seen with 10 nM VCR in A549 cells following 48 h treatment. In summary, there may be a significant contribution of transcriptional activation to multi-drug resistance. However, this is cell selective and is not necessarily dependent on PXR mediated effects.

Base Sequence↗
PubMed2006

Determination of vincristine in infant plasma by liquid chromatography-atmospheric pressure chemical ionization-mass spectroscopy.

An LC-MS method using APCI has been developed and validated for the determination of the anticancer drug vincristine in human plasma, using vinblastine as internal standard. Following solid-phase extraction (SPE) of the sample, the lower limit of quantitation (LLOQ) was 0.18 ng/ml, the lower limit of detection was 0.09 ng/ml, and the linear calibration range was 0.18-180 ng/ml. This method has been used to measure plasma concentrations of vincristine from 0.08 to 24 h post bolus in 29 infants as part of a pharmacokinetic study. Concentrations of vincristine at 24 h were 0.2-1.36 ng/ml.

Antineoplastic Agents, Phytogenic↗
PubMed2006

Diterpenoids from the roots of Euphorbia fischeriana.

From the dried roots of Euphorbia fischeriana, seven new diterpenoids, 3alpha,17-dihydroxy-ent-pimara-8(14),15-diene (1), 7beta,11beta,12beta-trihydroxy-ent-abieta-8(14),13(15)-dien-16,12-olide (2), 17-acetoxyjolkinolide B (3), 13beta-hydroxy-ent-abiet-8(14)-en-7-one (4), 12-deoxyphorbaldehyde-13-acetate (5) 12-deoxyphorbaldehyde-13-hexadecacetate (6), and 12-deoxyphorbol-13-(9Z)-octadecanoate-20-acetate (7), and two known compounds, 12-deoxyphorbol-13-decanoate (8) and prostratin (9), were isolated. The structures of the new compounds were elucidated on the basis of spectroscopic analysis. The structure of compound 1 was confirmed by single-crystal X-ray crystallography. Compounds 3 and 8 exhibited potent cytotoxic activity to Ramos B cells with IC50 values of 0.023 and 0.0051 microg/mL, respectively.

Antineoplastic Agents, Phytogenic↗
PubMed2006

Membership in genetic groups predicts Alzheimer disease.

The multiple polymorphisms contributing to Alzheimer disease (AD) have been difficult to identify. Three essentially sufficient risk sets were found using a fuzzy latent classification statistical model; that is, grade-of-membership analysis, and genotypes for APOE, APOCI, LDLr, cystatin C, and cathepsin D (180 cases, 120 controls). These were: (a) CST3:GA and CTSD:CT; (b) APOE44 and LDLr8:GG and LDLr13:TT; and (c) APOE34 and LDLr13:TC. Consonance with one of the groups and high aggregate membership carried >800-fold elevated risk for AD. The absence of these combinations defined low risk. APOE3/- with heterozygous promoter and receptor genotypes predicted long life without dementia.

Aged↗
PubMed2006

New nematicidal azaphilones from the aquatic fungus Pseudohalonectria adversaria YMF1.01019.

Two new azaphilone metabolites, named pseudohalonectrin A (1) and B (2), were isolated from the culture of the aquatic fungus Pseudohalonectria adversaria YMF1.01019, originally separated from submerged wood in Yunnan Province, China. Pseudohalonectrin A and B were assessed for their nematicidal activity against the pine wood nematode Bursaphelenchus xylophilus and their structures were defined after spectral analysis. This is the first report of secondary metabolites from any member of the genus Pseudohalonectria.

Animals↗
PubMed2006

Coherence detection: effects of frequency, frequency uncertainty, and onset/offset delays.

The detectability of a sequence of equal-frequency (coherent) tonal components embedded in random, multiburst maskers was evaluated. The masker was comprised of tonal components located in a time-by-frequency spectrogram with eight 30 ms time columns and 29 frequency rows ranging logarithmically from 200 to 5000 Hz. The probability that a tone occurred in any one cell of the spectrogram, p, was the independent variable. The signal and masker components were of equal duration and equal level. Using a yes/no procedure, threshold values of p were estimated for five signal frequencies (220, 445, 1000, 2245, 4490 Hz) and when the signal frequency was random. Thresholds were worst for the random-frequency signal and best for the fixed 1000 Hz signal. In additional conditions, the value of p was fixed and the signal components were delayed relative to the masker components. A 1 ms delay provided better sensitivity (d' grew from 0.5 to 1) for all but the lowest signal frequency tested. An analysis of no-signal trials revealed that false alarm rates were higher when components falling at the signal frequency were consecutive than when they were distributed across bursts. Thus, coherence rather than total energy at the signal frequency is important for signal detection.

Acoustic Stimulation↗
PubMed2006

[Factors influencing successful isolation of mesenchymal stem cells from human umbilical cord blood].

OBJECTIVE: Emerging evidences suggest that mesenchymal stem cells (MSCs) can be isolated from human umbilical cord blood (HUCB) and cultured in vitro, the same as the MSCs derived from bone marrow. However previous attempts to isolate MSCs from UCB showed a low rate of success (less than 30%). The present study was conducted to clarify the factors that influence the yields of MSCs from HUCB of different gestational age deliveries and to observe the bioactivity of MSCs derived from UCB. METHODS: HUCB units were divided into three groups: gestational age (GA) 40 w group (n = 11); GA 36 w group (n = 6); GA 32 w or less than 32 w group (n = 5), cultured with optimal culture conditions. The relationship of the yields of MSCs derived from HUCB with several factors such as GA, the collected volume of HUCB and the mononuclear cells (MNCs) count of UCB, and the relationship among these factors were investigated. The bioactivity was observed by drawing the growth curve, calculating the population doubling, counting the fibroblast colony forming units (CFU-F) and detecting the surface antigen expression of MSCs by flow cytometry. RESULTS: The success rate of generating MSCs cells was up to 54.5%. There were some correlations between the success rate and such factors as the MNCs count, the GA and the volume of UCB. The rate could be enhanced to 83.3% when the MNCs count was more than 1.25 x 10(8)/L. There was a negative correlation between the MNCs count in the same HUCB volume and the gestational age. The count of CFU-F varied with gestational age, the count of CFU-F was higher in smaller gestational age than the older. In the primary culture some cells displayed a fibroblast-like morphology and expressed MSCs-related antigens CD29, CD105, and the expression rate of these antigens were enhanced from 62.1% to 85.0% in one passage. The hematopoietic cells antigens CD34 and CD45 were less than 3% all the time. CONCLUSIONS: The success rate could be increased when the MNCs count was more then 1.25 x 10(8)/L. There was a negative correlation between the MNCs count of the same UCB volume and the gestational age, the activity to form the CFU-F of UCB varied with gestational age; isolation of MSCs from UCB of pre-term deliveries may be relatively easier as compared to those from full term deliveries.

Cell Count↗
PubMed2005

Single-bounce monocapillaries for focusing synchrotron radiation: modeling, measurements and theoretical limits.

Single-bounce hollow glass capillaries with ellipsoidal shapes have been used at the Cornell High Energy Synchrotron Source recently for various microbeam experiments, with focal spot sizes from 12 to 23 microm, divergences from 2 to 8 mrad, intensities up to 450 times the intensities of incident X-rays, and working distances up to 55 mm. Simple formulae are developed in this paper to explain capillary performance given the X-ray source size, capillary dimensions and slope errors. Capillary length is optimized for best focusing performance. Capillary fabrication accuracy is reported and capillary X-ray tests confirm the focusing properties expected from formulae. The application of capillaries to third-generation X-ray sources and future energy-recovery linac X-ray sources are discussed.

Capillary Action↗
PubMed2005

Solvent effects on IR and VCD spectra of helical peptides: DFT-based static spectral simulations with explicit water.

Simulations of IR and VCD spectra are carried out for model alpha-helical, 3(10)-helical, and 3(1)-helical (polyProII-like) oligopeptides, with up to 21 amide groups, and including explicit consideration of effects of directly hydrogen-bonded solvent (water). Parameters used were obtained from ab initio density functional theory (DFT) computations of force field, atomic polar and axial tensors for oligopeptides of 5 to 7 amides, whose structures were constrained in (phi,psi) to target the secondary structure type but otherwise fully optimized. By comparison with experimental data as well as with calculations for identical but isolated (gas phase) peptides, the computed effects of an inner shell of aqueous solvent on the vibrational spectra of helical oligopeptides are illustrated. The interaction with solvent causes significant frequency shifts of the amide bands, but only minor changes in the characteristic IR intensity distributions and splittings and the VCD band shapes. Better agreement with experimental band shapes is achieved for the alpha-helical amide I' (N-deuterated) VCD by inclusion of explicit solvent in the calculations. Some improvements are also observed in theoretical VCD predictions for 13C labeled alpha-helical peptides when solvated models are used. However, the qualitative isotopic splitting patterns are preserved and just shifted in frequency due to consistent, solvent independent interamide coupling constants. The critical match of experiment and theory for relative positions of transitions in peptides with specifically separated 13C=O labels, including and neglecting solvent, confirms the stability of the coupling interactions. Despite these solvation effects, the calculated VCD band shape of the amide I mode is shown to be a reliable conformational probe, since it remains basically insensitive to frequency shifts caused by environment. Thus theoretical VCD simulations, even vacuum calculations, are shown to provide useful spectral predictions for solution-phase peptides.

Circular Dichroism↗
PubMed2005

IR study of cross-strand coupling in a beta-hairpin peptide using isotopic labels.

Model beta-hairpin peptides can be used to develop understanding of fundamental elements of beta-sheet secondary structure formation and stability. We have studied two 13C-labeled variants of a beta-hairpin peptide modified from a design originally proposed by Gellman: Arg-Tyr-Val-Glu-Val-Aib-Gly-Lys-Lys-Ile-Leu-Gln. (In this peptide, the two italicized residues form a beta-turn, while 13C-labels are on the amide C=O of Val3, Lys8 in HBG-L and Val3, Ile10 in HBG-S.) Both these peptides are labeled on opposite strands of the hairpin, but differ in the labeling pattern. One (HBG-L) forms a large (14-atom) H-bonded ring of labeled C=Os, while the other (HBG-S) forms a small (10-atom) H-bonded ring. These impact the amide I infrared spectra, with HBG-L having a 13C frequency and intensity higher than that of HBG-S, in good agreement with our spectral simulations based on quantum mechanically derived force fields. The thermal behavior of both peptides yields a broad thermal transition and lacks an isosbestic point. The 13C band for HBG-L has the largest intensity change with temperature, distinct from the 12C change and the HBG-S 13C change.

Amino Acid Sequence↗
PubMed2005

Nucleoside transporter expression and function in cultured mouse astrocytes.

Uptake of purine and pyrimidine nucleosides in astrocytes is important for several reasons: (1) uptake of nucleosides contributes to nucleic acid synthesis; (2) astrocytes synthesize AMP, ADP, and ATP from adenosine and GTP from guanosine; and (3) adenosine and guanosine function as neuromodulators, whose effects are partly terminated by cellular uptake. It has previously been shown that adenosine is rapidly accumulated by active uptake in astrocytes (Hertz and Matz, Neurochem Res 14:755-760, 1989), but the ratio between active uptake and metabolism-driven uptake of adenosine is unknown, as are uptake characteristics for guanosine. The present study therefore aims at providing detailed information of nucleoside transport and transporters in primary cultures of mouse astrocytes. Reverse transcription-polymerase chain reaction identified the two equilibrative nucleoside transporters, ENT1 and ENT2, together with the concentrative nucleoside transporter CNT2, whereas CNT3 was absent, and CNT1 expression could not be investigated. Uptake studies of tritiated thymidine, formycin B, guanosine, and adenosine (3-s uptakes at 1-4 degrees C to study diffusional uptake and 1-60-min uptakes at 37 degrees C to study concentrative uptake) demonstrated a fast diffusional uptake of all four nucleosides, a small, Na(+)-independent and probably metabolism-driven uptake of thymidine (consistent with DNA synthesis), larger metabolism-driven uptakes of guanosine (consistent with synthesis of DNA, RNA, and GTP) and especially of adenosine (consistent with rapid nucleotide synthesis), and Na(+)-dependent uptakes of adenosine (consistent with its concentrative uptake) and guanosine, rendering neuromodulator uptake independent of nucleoside metabolism. Astrocytes are accordingly well suited for both intense nucleoside metabolism and metabolism-independent uptake to terminate neuromodulator effects of adenosine and guanosine.

Adenosine↗
PubMed2005

11-Methoxyviburtinal, a new iridoid from Valeriana jatamansi.

Five compounds of iridoids, lignan and phenylpropanoid glycosides were isolated from the roots of Valeriana jatamansi by column chromatography. Their structures were elucidated as 11-methoxyviburtinal (1), baldrinal (2), prinsepiol-4-omicron-beta-D-glucoside (3), coniferin (4), and hexacosanic acid (5) by spectroscopic analysis. 11-Methoxyviburtinal was a new compound, and others were isolated from the plant for the first time.

Iridoids↗
PubMed2005

Apolipoprotein gene E4 allele promoter polymorphisms as risk factors for Alzheimer's disease.

Alzheimer's disease is a complex neurodegenerative disorder, characterized by progressive cognitive decline and distinct neuropathology. The apolipoprotein gene E4 allele (APOE 4) is a major risk factor for the disease. Promoter polymorphisms at -491 and -427 may also contribute to the risk. We examined the two polymorphisms in 178 Alzheimer's patients and 141 controls. The -491AA genotype was overrepresented among the patients (68 versus 54%, P=0.01). However, in patients who were APOE4 carriers, the -491AA genotype more than doubled the risk [odds ratio (OR)=2.5; 95% confidence interval (CI)=1.2-5.4], especially in combination with -427TT [odds ratio (OR)=3.3; 95% confidence interval (CI)=1.5-7.7]. Moreover, the -491A/-427T/APOE4/APOC1A haplotype was threefold higher for patients. These results contribute to the evidence that regulation of APOE4 expression modulates risk for Alzheimer's disease.

Alzheimer Disease↗