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Biomedical subjects

Zhen Yang

Publications and source records attributed to Zhen Yang.

At least 19 recordsLinked to original sources
PubMed2026

RUNX3: a regulator of macrophage apoptosis with positive prognostic impact in sepsis.

BACKGROUND: Sepsis, a life-threatening condition, remains a leading cause of mortality globally. Transcription factors (TFs) play a pivotal role in its pathogenesis. RUNX3, a member of the RUNX family, has been implicated in immune regulation, but its function in sepsis remains unclear. OBJECTIVE: To determine whether RUNX3 expression is altered in sepsis and associated with patient prognosis, and to investigate its function and potential transcriptional regulatory targets in macrophages. METHODS: We analyzed RNA-seq data from sepsis patients to identify differentially expressed TFs and examined the prognostic impact of RUNX3 by Kaplan-Meier survival analysis. RUNX3 was stably overexpressed in RAW264.7 macrophages, and cell proliferation and apoptosis were assessed by EdU and flow cytometry assays. RNA-seq of RUNX3-overexpressing cells was performed to identify potential transcriptional regulatory targets, a subset of which was validated by RT-qPCR. RESULTS: RUNX3 expression was downregulated in sepsis patients, and low RUNX3 expression was associated with poor prognosis. RUNX3 overexpression promoted proliferation and inhibited apoptosis in RAW264.7 cells. Integrating RNA-seq with public RUNX3 binding data identified 89 potential transcriptional regulatory targets, among which Tgfbr3, Tgfbi, Il2rb, Gbp2, Gzmb, and Ptgds were confirmed as RUNX3-responsive by RT-qPCR. High expression of these targets was associated with favorable prognosis in sepsis patients. CONCLUSION: RUNX3 is closely associated with the prognosis of sepsis, and its overexpression promotes proliferation and suppresses apoptosis in macrophages, potentially by regulating downstream target genes, providing a novel perspective on sepsis pathogenesis.

Apoptosis↗
PubMed2024

Comprehensive analysis of the expression, prognostic, and immune infiltration for COL4s in stomach adenocarcinoma.

BACKGROUND: Collagen (COL) genes, play a key role in tumor invasion and metastasis, are involved in tumor extracellular matrix (ECM)-receptor interactions and focal adhesion pathways. However, studies focusing on the diagnostic value of the COL4 family in stomach adenocarcinoma (STAD) are currently lacking. METHODS: The TCGA database was employed to retrieve the clinical features and RNA sequencing expression profiles of patients with STAD. We conducted an investigation to examine the expression disparities between STAD and adjacent normal tissues. Kaplan-Meier survival analysis was utilized to assess their prognostic significance, while Spearman correlation analysis was employed to determine their association with immune checkpoint genes and immunomodulatory molecules. Furthermore, GO and KEGG analyses were performed on the COL4s-related genes, revealing potential biological pathways through gene set enrichment analysis (GSEA). Subsequently, we explored the extent of immune infiltration of the COL4 family in STAD using the TIMER database. Lastly, the expression levels of the COL4 family in STAD were further validated through quantitative PCR (qPCR) and western blot techniques. RESULTS: The expression levels of COL4A1/2 were significantly upregulated, while COL4A5/6 were conspicuously downregulated in STAD. The survival analysis revealed that the upregulated COL4s indicated poorer overall survival, first progression and post-progression survival outcomes. Additionally, our findings demonstrated a positive correlation between the expressions of COL4A1/2/3/4 and the infiltration of immune cells, including CD8 + T cells, dendritic cells, macrophages, neutrophils and CD4 + T cells. Further correlation analysis uncovered a favorable association between the expression of COL4A1/2/3/4 and various crucial immunomodulatory molecules, immunological checkpoint molecules, and chemokines. Quantitative PCR analysis confirmed that the expression patterns of COL4A1/3/4/6 genes aligned with the finding from the TCGA database. However, gastric cancer cells exhibited downregulation of COL4A2. Consistently, the protein level of COL4A1 was elevated, whereas the protein level of COL4A2 was reduced in the gastric cancer cell lines. CONCLUSION: COL4s could potentially serve as biomarkers for diagnosing and predicting the prognosis of STAD.

Stomach Neoplasms↗
PubMed2007

In vitro shear stress modulates antithrombogenic potentials of human endothelial progenitor cells.

BACKGROUND: Recent study suggested that endothelial progenitor cells (EPCs), a novel therapeutic approach for endothelial dysfunction, present limited antithrombogenic potentials. However, few attempts have been done to improve the antithrombogenic potentials of EPCs. Our previous study proved that in vitro shear stress contributes to the increase in t-PA production by human EPCs. Here, we further investigated whether in vitro shear stress contributes to the secretion of antithrombogenic substances including plasminogen activator inhibitor-1 (PAI-1) and prostaglandin I(2) (PGI(2)) by human EPCs. METHODS: The peripheral blood mononuclear cells of healthy subjects were induced into EPCs. Then the human EPCs were treated with four levels of shear stress including stationary condition low media and high flow shear stress. The production of PAI-1 and 6-keto-prostaglandin F1(1alpha)(6-Keto-PGF(1alpha)) by human EPCs with shear stress treatment were measured. RESULTS: In vitro medium and high flow shear stress inhibited PAI-1 secretion by human EPCs, but low flow shear stress had no effect on PAI-1 secretion by human EPCs. All levels of shear stress significantly increased 6-Keto-PGF(1alpha )production by human EPCs in a dose-dependent manner. CONCLUSIONS: The present study demonstrates that in vitro shear stress can promote PGI(2 )secretion and inhibit PAI-1 secretion by human EPCs, which improves the antithrombogenic potentials of human EPCs.

6-Ketoprostaglandin F1 alpha↗
PubMed2006

Micropore x-ray optics using anisotropic wet etching of (110) silicon wafers.

To develop x-ray mirrors for micropore optics, smooth silicon (111) sidewalls obtained after anisotropic wet etching of a silicon (110) wafer were studied. A sample device with 19 microm wide (111) sidewalls was fabricated using a 220 microm thick silicon (110) wafer and potassium hydroxide solution. For what we believe to be the first time, x-ray reflection on the (111) sidewalls was detected in the angular response measurement. Compared to ray-tracing simulations, the surface roughness of the sidewalls was estimated to be 3-5 nm, which is consistent with the atomic force microscope and the surface profiler measurements.

Anisotropy↗
PubMed2006

Increased brachial-ankle pulse wave velocity is associated with impaired endothelial function in patients with coronary artery disease.

BACKGROUND: Pulse wave velocity and flow-mediated vasodilation (FMD) are widely used as noninvasive modalities for evaluating atherosclerosis. However, it is not known whether pulse wave velocity is related to FMD in patients with coronary artery disease (CAD). Therefore, the present study was designed to investigate the alteration in brachial-ankle pulse wave velocity (baPWV) and endothelial function in CAD patients. METHODS: Thirty-three patients with CAD and thirty control subjects were recruited for this study. baPWV was measured non-invasively using a VP 1000 automated PWV/ABI analyzer (PWV/ABI, Colin Co. Ltd., Komaki, Japan). Endothelial function as reflected by FMD in the brachial artery was assessed with a high-resolution ultrasound device. RESULTS: baPWV was increased in CAD patients compared with control subjects [(1756.1 +/- 253.1) cm/s vs (1495.3 +/- 202.3) cm/s, P < 0.01]. FMD was significantly reduced in CAD patients compared with control subjects [(5.2 +/- 2.1)% vs (11.1 +/- 4.4)%, P < 0.01]. baPWV correlated with FMD (r = -0.68, P < 0.001). The endothelium-independent vasodilation induced by sublingual nitroglycerin in the brachial artery was similar in the CAD group compared with the control group. CONCLUSIONS: CAD is associated with increased baPWV and endothelial dysfunction. Increased baPWV parallels diminished endothelial function. Our data therefore suggest that baPWV can be used as a noninvasive surrogate index in clinical evaluation of endothelial function.

Aged↗
PubMed2006

Synthetic study of 1,3-butadiene-based IMDA approach to construct a [5-7-6] tricyclic core and its application to the total synthesis of C8-epi-guanacastepene O.

An efficient intramolecular Diels-Alder (IMDA) strategy for the construction of the [5-7-6] tricyclic core (18) of guanacastepenes has been developed from cis- and trans-1,3-butadiene-tethered 4-oxopent-2-ynoic acid ethyl esters 10 and 11. This method facilitates the synthesis of C8-epi-guanacastepene O (36) in a very efficient manner.

Butadienes↗
PubMed2006

Oxidative DNA cleavage promoted by multinuclear copper complexes: activity dependence on the complex structure.

Polynuclear copper complexes with two or three Cu(BPA) (BPA, bis(2-pyridylmethyl)amine) motifs, [Cu2(mTPXA)Cl4]3 H2O (1), [Cu2(pTPXA)Cl4]3 H2O (2), [Cu3(HPTAB)Cl5]Cl3 H2O (3) (mTPXA = N,N,N',N'-tetra-(2-pyridylmethyl)-m-xylylene diamine; pTPXA = N,N, N',N'-tetra-(2-pyridylmethyl)-p-xylylenediamine; HPTAB = N,N,N',N',N'',N''-hexakis(2-pyridylmethyl)-1,3,5-tris-(aminomethyl)benzene) have been synthesized and characterized. The crystal structures of compounds 2 and 3 showed each Cu(BPA) motif had a 4+1 square-pyramidal coordination environment with one chloride occupying the apical position and three N atoms from the same BPA moiety together with another Cl atom forming the basal plane. Fluorescence and circular dichroism (CD) spectroscopy studies indicated that the DNA binding followed an order of 3>2>1 in the compounds. These complexes cleave plasmid pUC19 DNA by using an oxidative mechanism with mercaptopropionic acid (MPA) as the reductant under aerobic conditions. Dinuclear Cu2+ complexes 1 and 2 showed much higher cleavage efficiency than their mononuclear analogue [Cu(bpa)Cl2] at the same [Cu2+] concentration, suggesting a synergistic effect of the Cu2+ centers. Moreover, the meta-dicopper centers in complex 1 facilitated the formation of linear DNA. Interestingly, the additional copper center to the meta-dicopper motif in complex 3 decreased the cleavage efficacy of meta-dicopper motif in complex 1, although it is able to cleave DNA to the linear form at higher [Cu2+] concentrations. Therefore, the higher DNA binding ability of complex 3 did not lead to higher cleavage efficiency. These findings have been correlated to the DNA binding mode and the ability of the Cu2+ complexes to activate oxygen (O2). This work is a good example of the rational design of multinuclear Cu2+ artificial nuclease and the activity of which can be manipulated by the geometry and the number of metal centers.

Amines↗
PubMed2006

Identification of four novel mutations in the HNF-1A gene in Chinese early-onset and/or multiplex diabetes pedigrees.

BACKGROUND: Mutations in the hepatocyte nuclear factor-1A gene cause the type 3 form of maturity-onset diabetes of the young (MODY3). This study was undertaken to determine mutations and sequence variations of the HNF-1A gene in Chinese with familial early-onset and/or multiplex diabetes mellitus. METHODS: We screened all ten exons of the HNF-1A gene, including exon/intron junctions, by direct sequencing in 272 unrelated Chinese, including 80 healthy controls and 192 probands of early-onset and/or multiplex diabetes pedigrees. RESULTS: In addition to one silent mutation of c.864 G > C [p.G288G] in exon4 at codon 288, which had been reported previously, a total of four novel mutations including two missense mutations (c.245C > T [p.T82M] and c. 390 G > T [p.Q130H]) and one frameshift mutation P353fsdelACGGGCCTGGAGC and one silent mutation c.759 G > T [p.G253G] were identified. Moreover, eleven substitutions were identified in 192 probands. Of these, three variants (-8 G > A, -128 T > G and IVS2 + 21 G > A) were not observed in 80 healthy controls and one of them (-8 G > A) was not reported previously and the two promoter variants co-segregated with diabetes. The genotype and allele frequencies of the other eight variants in the diabetic patients were not significantly different from those in the healthy controls. No significant relationships were observed between the eight variants of the HNF-1A gene and clinical variables (plasma glucose, insulin, C-peptide and fasting lipid profile). CONCLUSION: The prevalence of structural mutations in the HNF-1A gene responsible for familial early-onset and/or multiplex diabetes appears to be rare among Chinese patients.

Adult↗
PubMed2006

Investigation of the influencing factors on severe acute respiratory syndrome among health care workers.

OBJECTIVE: To investigate the protective factors and risk factors of nosocomial infection of severe acute respiratory syndrome (SARS) among health care workers (HCWs), and thus provide the scientific basis for prevention and control of nosocomial infection. METHODS: With the case-control study, a standardized questionnaire was used for data collection in three general hospitals where nosocomial infection had occurred. Univariate analysis was done at first. All concerned factors about SARS infection were scanned by using Chi-square test and Fisher's exact test one by one, and determined as to whether they were risk factors or protective factors according to odd ratio (OR) score. Then, multivariate unconditional logistic regression analysis was used to re-analyze the picked-out factors for finding out which factors played independent roles. RESULTS: Twenty-two factors (nineteen protective factors and three risk factors), among the total fifty-six factors, were significantly associated with SARS infection. Multivariate unconditional logistic regression revealed that factors such as double exposure suits (OR=0.053), education (OR=0.072), gloves (OR=0.102), hands sterilized by iodine (OR=0.231), room air ventilation (OR=0.32), were significantly protective; conversely, tracheal intubation (OR=30.793) was a significant risk factor. CONCLUSION: Strict defense and antisepsis measures were pivotal in preventing SARS infection among high-risk medical personnel. Education about associated knowledge and effective air ventilation were also important factors.

Adolescent↗
PubMed2006

Cardiac markers and their point-of-care testing for diagnosis of acute myocardial infarction.

Acute myocardial infarction (AMI) is the world's leading cause of mortality and morbidity. Therefore, quick and reliable diagnostics of AMI is extremely critical. Compared to the traditionally used central laboratory tests (CLT), which can be time-consuming and expensive, point-of-care testing (POCT) for AMI-indicative cardiac markers provides a convenient means for rapid diagnostic assays to be performed at the site of patient care delivery. In this article, the etiology and diagnosis of AMI are introduced, and some typical cardiac markers and their clinical applications are reviewed. Furthermore, the various POC cardiac marker devices that are currently available, the benefits of using cardiac marker POC assays, and challenges that cardiac marker POCT are facing are also discussed.

Biomarkers↗
PubMed2006

Splenic vasculopathy in portal hypertension patients.

AIM: To investigate the interaction between portal hypertension, splanchnic hyperdynamic circulation and splanchnic vasculopathy by observing splenic arterial and venous pathological changes and the ro1e of extra-cellular matrix in the pathogenesis of portal hypertensive vasculopathy by measuring the expression of type I and type III procollagen mRNA in splenic venous walls of portal hypertensive patients. METHODS: Morphological changes of splenic arteries and veins taken from portal hypertensive patients (n=20) and normal controls (n=10) were observed under optical and electron microscope. Total RNA was extracted and the expression of type I and type III procollagen mRNA in splenic venous walls of portal hypertensive patients (n=20) was semi-quantitatively detected using reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Under optical microscope, splenic arterial intima was destroyed and internal elastic membrane and medial elastic fibers of the splenic arterial walls were degenerated and broken. Splenic venous intima became remarkably thick. Endothelia1 cells were not intact with formation of mural thrombus. The tunica media became thickened significantly due to hypertrophy of smooth muscles. Fibers and connective tissues were increased obviously. Under electron microscope, smooth muscle cells of the splenic arteries were degenerated and necrotized. Phenotypes of smooth muscle cells changed from constrictive into synthetic type. Red blood cells and platelets accumulated around the damaged endothelial cells. Synthetic smooth muscle cells were predominant in splenic veins and their cytoplasma had plentiful rough endoplasmic reticulum ribosomes and Golgi bodies. Along the vascular wall, a lot of collagen fibers were deposited, the intima was damaged and blood components accumulated. There was no significant difference in the expression of type I procollagen mRNA in splenic venous wall between the patients with portal hypertension and those without portal hypertension (P>0.05), but the expression of type III procoagen mRNA was significantly stronger in the patients with portal hypertension than in those without portal hypertension (P<0.01). CONCLUSION: Type III procollagen and collagen might be important extra-cellular matrix resulting in neointimal formation and vascular remodeling in the pathogenesis of portal hypertensive vasculopathy. The pathological changes in splenic arteries and veins exist in portal hypertension patients. There might be an interaction between portal hypertension, splanchnic hyperdynamic circulation and splanchnic vasculopathy.

Adult↗
PubMed2006

Effects of fluid shear stress on eNOS mRNA expression and NO production in human endothelial progenitor cells.

The increases in physiological levels of fluid shear stress have beneficial effects on vascular homeostasis. Endothelial progenitor cells (EPCs) play an important role in the maintenance of endothelial integrity. We hypothesized that shear stress-mediated vascular protection is related to the upregulation of endothelial nitric oxide synthase expression in EPCs. The human EPCs exposed to in vitro shear stress levels of 5, 15 and 25 dyn/cm(2) for 4 h. In vitro shear stress, in a dose-dependent fashion, increased the endothelial nitric oxide synthase mRNA expression and the nitric oxide production in human EPCs. The present findings for the first time provide novel insights into the mechanisms of the physiological levels of fluid shear stress on the regulation of human EPC biologic phenotype as a potential factor, which might contribute to vascular protective activities in humans although evidence is indirect.

Adult Stem Cells↗
PubMed2006

[Experimental research of therapeutic effect on hepatocellular carcinoma of targeting SMYD3 gene inhibition by RNA interference].

OBJECTIVE: To determine the potential of SMYD3 as a therapeutic target for hepatocellular carcinoma (HCC) by potent and highly sequence-specific RNA interference (RNAi) technique. METHODS: The mRNA of SMYD3 was detected by RT-PCR in different HCC cell lines, such as HepG2, Hep3B and SMMC7721. Recombinant SMYD3 shRNA plasmid Pgenesil-1-s was constructed and transfected into HepG2 cells, and Western blot was used to identify the down regulation of SMYD3 protein expression after transfection. MTT and flow cytometry analysis (FCM) were respectively applied to analysis cell proliferation and apoptosis. In vivo study was carried out by injecting recombinant SMYD3 shRNA plasmids into transplanted tumors of nude mice. RESULTS: The expression of SMYD3 mRNA was abundant in HCC cell lines HepG2, Hep3B, SMMC7721, whereas none in normal hepatic cell line L-02. RNA interference was able to suppress SMYD3 expression greatly and then inhibited cell growth effectively and induced apoptosis of HepG2 cells efficiently. After injection of recombinant SMYD3 shRNA plasmid, transplanted tumors grew slowly and reduced in size and weight when compared with those of control groups (P < 0.01). CONCLUSIONS: SMYD3 plays a major role in occurrence and progress of HCC. Inhibition of SMYD3 by RNAi can induce apoptosis in HepG2 cells and suppress tumor growth in nude mice. Therefore SMYD3 could be an ideal therapeutic target for HCC.

Animals↗
PubMed2006

Shear stress contributes to t-PA mRNA expression in human endothelial progenitor cells and nonthrombogenic potential of small diameter artificial vessels.

Seeding endothelial progenitor cells (EPCs) onto the surface of vascular grafts has been proved to be a promising strategy to improve nonthrombogenic potentials of small diameter artificial vessels. Here, we investigated whether in vitro shear stress modulates the tissue-type plasminogen activator (t-PA) secretion and mRNA expression in human EPCs and improves patency of the EPC-seeded polyurethane small diameter vascular grafts implanted in the canine carotid artery in vivo. In vitro shear stress, in a dose-dependent manner, increased t-PA secretion and mRNA expression of human EPCs. The in vivo implantation of EPC-seeded vascular grafts remained highly patent in shear stress pretreatment compared with stationary condition. The present findings demonstrate for the first time that in vitro shear stress can enhance t-PA secretion and gene expression in human EPCs, which contributes to improvement in nonthrombogenic potentials of EPC-seeded small diameter artificial vessels with maintenance of in vivo highly patency rate.

Animals↗
PubMed2006

Intestinal permeability in rats with CCl4-induced portal hypertension.

AIM: To investigate the intestinal barrier changes in rats with CCl4-induced portal hypertension. METHODS: The permeability of intestinal barrier detected by Lanthanum as a tracer was evaluated in rats. Bacterial translocation and plasma endotoxin were also determined. RESULTS: The incidence of bacterial translocation was 85% in rats with CCl4-induced portal hypertension, which was significantly higher than that in control rats (20%, P<0.01). Plasma endotoxin level was significantly higher in experimental group than in control group. Permeability of the epithelial mucosa and pathological alteration were increased in the ileum and the microvilli became shorter and thinner in rats with portal hypertension. CONCLUSION: Bacterial translocation occurs in rats with CCl4-induced portal hypertension and increased permeability between epithelial cells contributes to the translocation.

Animals↗