Biomedical subjects

Xiao Zhou

Publications and source records attributed to Xiao Zhou.

14 recordsLinked to original sources

PubMed2026

OLR1 drives gastric cancer progression through NF-κB activation and immunosuppressive macrophage polarization.

Gastric cancer remains a leading cause of cancer-related mortality worldwide, and the identification of clinically relevant biomarkers is critical for improving patient outcomes. Oxidized low-density lipoprotein receptor 1 (OLR1) has been implicated in tumor progression; however, its role in gastric cancer and the tumor microenvironment remains unclear. OLR1 expression and clinical significance were analyzed using The Cancer Genome Atlas (TCGA) dataset and validated in gastric cancer cell lines. Gain- and loss-of-function experiments, together with in vitro and in vivo assays, were performed to investigate the biological functions and underlying mechanisms of OLR1 in gastric cancer progression. OLR1 was significantly upregulated in gastric cancer and associated with unfavorable prognosis. Functional analyses demonstrated that OLR1 promoted gastric cancer cell proliferation, migration, and tumor growth. Mechanistically, OLR1 activated NF-κB signaling and facilitated macrophage polarization toward the M2 phenotype, thereby contributing to a protumorigenic microenvironment. OLR1 promotes gastric cancer progression through activation of NF-κB signaling and modulation of macrophage polarization. These findings identify OLR1 as a potential prognostic biomarker and therapeutic target for gastric cancer.

Humans↗

PubMed2025

Network-based drug repurposing for psychiatric disorders using single-cell genomics.

Neuropsychiatric disorders lack effective treatments due to a limited understanding of the underlying cellular and molecular mechanisms. To address this, we integrated population-scale single-cell genomics data and analyzed 23 cell-type-level gene regulatory networks across schizophrenia, bipolar disorder, and autism. Our analysis revealed potential druggable transcription factors co-regulating known risk genes that converge into cell-type-specific co-regulated modules. We applied graph neural networks on those modules to prioritize novel risk genes and leveraged them in a network-based drug repurposing framework to identify 220 drug molecules with the potential for targeting specific cell types. We found evidence for 37 of these drugs in reversing disorder-associated transcriptional phenotypes. Additionally, we discovered 335 drug-cell quantitative trait loci (eQTLs), revealing genetic variation's influence on drug target expression at the cell-type level. Our results provide a single-cell network medicine resource that provides potential mechanistic insights for advancing treatment options for neuropsychiatric disorders.

Drug Repositioning↗

PubMed2006

The key role of chlorocatechol 1,2-dioxygenase in phytoremoval and degradation of catechol by transgenic Arabidopsis.

Transgenic exploitation of bacterial degradative genes in plants has been considered a favorable strategy for degrading organic pollutants in the environment. The aromatic ring characteristic of these pollutants is mainly responsible for their recalcitrance to degradation. In this study, a Plesiomonas-derived chlorocatechol 1,2-dioxygenase (TfdC) gene (tfdC), capable of cleaving the aromatic ring, was introduced into Arabidopsis (Arabidopsis thaliana). Morphology and growth of transgenic plants are indistinguishable from those of wild-type plants. In contrast, they show significantly enhanced tolerances to catechol. Transgenic plants also exhibit strikingly higher capabilities of removing catechol from their media and high efficiencies of converting catechol to cis,cis-muconic acid. As far-less-than-calculated amounts of cis,cis-muconic acid were accumulated within the transgenic plants, existence of endogenous TfdD- and TfdE-like activities was postulated and, subsequently, putative orthologs of bacterial tfdD and tfdE were detected in Arabidopsis. However, no TfdC activity and no putative orthologs of either tfdC or tfdF were identified. This work indicates that the TfdC activity, conferred by tfdC in transgenic Arabidopsis, is a key requirement for phytoremoval and degradation of catechol, and also suggests that microbial degradative genes may be transgenically exploited in plants for bioremediation of aromatic pollutants in the environment.

Arabidopsis↗

PubMed2006

[Inhibitory effects of cyclooxygenase-2 inhibitor celecoxib on growth and angiogenesis of human liver cancer HepG2 cell xenografts in small nude mice].

BACKGROUND & OBJECTIVE: Cyclooxygenase-2 (COX-2) is closely correlated to genesis of tumors, particularly digestive tract tumors, and its inhibitor has antitumor effect. This study was to investigate the inhibitory effects of COX-2 inhibitor celecoxib on growth and angiogenesis of human liver cancer HepG2 cell xenografts in small nude mice. METHODS: HepG2 cells were transplanted into the dorsal subcutaneous tissue of athymic nude mice. The mice were treated with celecoxib 4 days after transplantation, and were killed 58 days later. Tumor volume and weight were measured. The expression of COX-2, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and angiopoietin-2 (Ang-2) were detected by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR), and microvessel density (MVD) was observed by immunohistochemistry. RESULTS: The average tumor volume was significantly smaller and the average tumor weight was significantly lighter in celecoxib group than in control group [(709.11+/-108.53) mm3 vs. (1,417.55+/-69.50) mm3, and (2.63+/-0.34) g vs. (5.32+/-0.98) g, P<0.01]. The inhibitory rate of tumor growth was 55.21%. The expression levels of COX-2, VEGF, bFGF and Ang-2, and MVD were significantly lower in celecoxib group than in control group (2.43+/-0.29 vs. 4.50+/-0.25, 2.80+/-0.30 vs. 5.49+/-0.58, 2.23+/-0.41 vs. 4.03+/-0.47, 2.88+/-0.25 vs. 5.53+/-0.54, and 29.27+/-1.52 vs. 128.24+/-9.82, P<0.01, respectively). COX-2 expression was positively correlated to VEGF, bFGF and Ang-2 expression and MVD (r=0.862, r=0.882, r=0.857, r=0.837,P<0.01, respectively). CONCLUSIONS: Celecoxib inhibits the growth and angiogenesis of HepG2 cell xenografts in nude mice effectively via suppressing the expression of COX-2.

Angiopoietin-2↗

PubMed2006

[Free anterolateral thigh flap for repairing the defects of oral cavity and maxillofacial].

OBJECTIVE: To investigate the outcomes following the tumor resection of oral cavity and maxillofacial and reconstruction with free anterolateral thigh flaps (ALT). METHODS: Thirty one patients underwent ALT reconstruction following the tumor resection from Dec. 2004 to Dec. 2005. Among them, 17 cases were squamous cell carcinoma (SCC) of tongue, 6 cases of buccal SCC and 8 other malignant. The size of the ALT flaps ranged from 4 to 8 cm in width and 6 to 23 cm in length. Tracheotomy were performed for 4 cases intraoperatively. RESULTS: The overall successful rate was 96.8%. Thirty cases survival no cancer, 1 case died of recurrent and no-controlled of lymph-node in 8 months after operation. Postoperative vessel thrombosis occurred in 3 flaps between 12 hours to 4 days after operation. Two of them were saved. The necrosis area of the third flap was 25%. CONCLUSIONS: The ALT was benefit to repair the defects of oral cavity and maxillofacial, and the donor place was more easily hidden and didn't not influence the outlook and function; the important normal functional framing such as teeth and bone should be preserved; the pedicle of vessel could't be twisted during the procedure of reconstruction to avoid vein oppressed; the size of flap should be suitable to defects in order to avoid flaps being crowd and blood clot; tracheotomy was safe while repairing the defect of hard and soft palate. Reconstructive surgical procedures;

Adult↗

PubMed2006

[Detection of micrometastasis in mediastinal lymph nodes in operable non-small cell lung cancers].

OBJECTIVE: Using the LUNX-mRNA as a marker and RT-PCR technique to assess mediastinal lymph nodes in patients with operable NSCLC, to evaluate at gene level the feasibility of this method in detection of micrometastasis in NSCLC and the necessity of systematic mediastinal lymphadenectomy during surgery. METHODS: Twenty patients with operable NSCLC were involved in this study. The mediastinal lymph nodes were taken during operation. RT-PCR assay was carried out to detect the LUNX-mRNA. Ten cases with benign lung disease were assayed by the same method as control. RESULTS: Seventy one mediastinal lymph nodes were obtained from 20 patients, 8 (11.3%) of which showed histologically metastasis with HE staining, while 23 (32.4%) were LUNX-mRNA positive by RT-PCR, P < 0.001. Micrometastasis was detected in 25.4% of all lymph nodes. LUNX-mRNA was found to be positive in 23.6% of lymph nodes from 15 patients with stage I A-II B NSCLC compared with 62.5% from 5 patients with stage III NSCLC, with a significant difference (P = 0.003). CONCLUSION: About 25.4% of mediastinal lymph nodes are with micrometastasis in patients with operable NSCLC. Systematic mediastinal lymphadenectomy is necessary to deal with the regional lymph nodes during surgery.

Adult↗

PubMed2005

CD44 expression is associated with increased survival in node-negative invasive breast carcinoma.

PURPOSE: CD44 is a multifunctional cell surface receptor with many known splice variants, some of which have been reported to play a role in tumor progression. The purpose of this study was to evaluate the prognostic significance of CD44 isoforms in early-stage, lymph node-negative invasive breast carcinoma. EXPERIMENTAL DESIGN: Immunohistochemical staining for CD44 isoforms was done on archival paraffin tissue sections of invasive breast carcinoma from a cohort of lymph node-negative patients who received no adjuvant tamoxifen or chemotherapy and who had a mean clinical follow-up period of 15 years. Immunohistochemical staining was done with antibodies to CD44s, the standard isoform of CD44, and to isoforms containing variant exon 6 (CD44v6); levels of staining were correlated with clinical outcome data. RESULTS: There was a trend towards increased disease-free survival for patients whose tumors had high anti-CD44s positivity (P = 0.05), and a significant association was observed between anti-CD44s positivity and disease-related survival (P = 0.04). Expression of CD44v6 isoforms did not correlate with clinical outcome. CONCLUSION: CD44 expression, as assessed by immunohistochemical staining with anti-CD44s, may be a favorable prognostic factor in patients with node-negative invasive breast carcinoma.

Adult↗

PubMed2005

Beta4 integrin subunit gene expression correlates with tumor size and nuclear grade in early breast cancer.

In vitro data support a role for the alpha6beta4 integrin in tumor cell migration and invasion, particularly in breast carcinoma cells, but clinical data on this potentially important integrin are limited. The beta4 integrin subunit has been shown to cluster with genes characteristic of basal/myoepithelial cells in cDNA microarray analyses of breast cancer, and the subset of breast cancers with increased expression of genes characteristic of basal/myoepithelial cells appears to be particularly aggressive. The purpose of this study was to determine whether alpha6beta4 integrin expression correlates with aggressive clinicopathologic features of breast cancer and whether expression of this integrin has prognostic significance in early breast cancer. We evaluated tumor expression of the beta4 integrin subunit gene in a cohort of patients with early invasive breast carcinoma by in situ hybridization and correlated expression levels with multiple clinicopathologic characteristics. We also evaluated expression of laminin-5 protein, the principal ligand of alpha6beta4, in this patient cohort. Although we observed a slight trend towards decreased disease-free survival for patients whose tumors had high beta4 gene expression and coexpression of laminin-5, this did not reach statistical significance (P=0.11). However, we did observe a correlation between beta4 mRNA expression and both tumor size (P=0.01) and tumor nuclear grade (P<0.01). These results do not demonstrate prognostic significance for beta4 gene expression and/or laminin-5 protein expression in early breast cancer, but increased beta4 gene expression in larger tumors and in higher grade tumors does support a potential role for the alpha6beta4 integrin in tumor progression.

Adult↗

PubMed2004

Adhesion-independent alpha6beta4 integrin clustering is mediated by phosphatidylinositol 3-kinase.

Clustering of cell-surface integrins is known to augment integrin-mediated signal transduction, but mechanisms of integrin clustering are poorly understood. Here we report that adhesion-independent clustering of alpha6beta4 integrin, known to be important in mediating tumor cell motility, is driven by phosphatidylinositol 3-kinase (PI3K) but does not require activation of the PI3K-Akt pathway. We observed clustering of alpha6beta4 in breast carcinoma cells after adhesion-independent cross-linking of the beta4 integrin subunit. Clustering was significantly blocked when cross-linking was performed in the presence of PI3K inhibitors LY294002 and wortmannin. In contrast, no significant inhibition of clustering was observed with protein kinase C inhibitor GF109203X, rapamycin, or heparin. Although alpha6beta4 clustering was blocked by PI3K inhibitors, clustering was not associated with increased PI3K lipid kinase activity or increased phosphorylation of Akt. A novel role for PI3K in alpha6beta4 integrin clustering is proposed.

Breast Neoplasms↗

PubMed2004

Chromogenic in situ hybridization for alpha6beta4 integrin in breast cancer: correlation with protein expression.

The alpha6beta4 integrin is the receptor for the basement membrane protein laminin-5. Recent studies suggest that alpha6beta4 integrin expression in invasive breast carcinomas may be a poor prognostic factor. Because we have not had reliable results with commercially available antibodies for the immunohistochemical detection of alpha6beta4 integrin in archival paraffin-embedded tissues, we designed a probe to detect beta4 integrin subunit mRNA in paraffin sections. In situ hybridization for beta4 mRNA was performed on paraffin-embedded tissue sections of 25 invasive breast carcinomas using a hyperbiotinylated oligonucleotide DNA probe. Immunohistochemical staining was performed on corresponding frozen tumor sections using two commercially available antibodies to the beta4 integrin subunit. All cases positive for beta4 protein by one or both antibodies were also positive for beta4 mRNA by in situ hybridization, but three cases with beta4 mRNA expression were negative by immunohistochemistry with both antibodies. These findings suggest that in situ hybridization appears to be a sensitive method for detecting beta4 integrin mRNA, but it appears to identify some cases that either lack beta4 protein or express variants not recognized with commercial antibodies directed to particular extracellular or cytoplasmic domains.

Adult↗

PubMed2004

Psychometric properties of the WHO Quality of Life questionnaire (WHOQOL-100) in patients with chronic diseases and their caregivers in China.

OBJECTIVE: To evaluate the psychometric properties of the WHO Quality of Life questionnaire (WHOQOL-100), a multi-dimensional, conceptualized, 100-item quality-of-life instrument. METHODS: A total of 460 patients in China with chronic diseases (including hypertension, schizophrenia, stroke, end-stage renal disease, head and neck cancer and breast cancer) and 418 family members who were their caregivers were assessed at baseline and one year later. FINDINGS: The WHOQOL-100 had acceptable internal consistency (alpha = 0.76-0.90 across domains). There were strong correlations between the domains of WHOQOL-100 and the dimensions of the General Quality of Life Inventory (alpha = 0.72-0.82 across related domains). Within domains most facet correlations were satisfactory, although some facets correlated more strongly with a domain other than that to which they had been assigned. Principal component analysis produced four factors accounting for 61% of the total variance. CONCLUSION: The WHOQOL-100 was able to discriminate between the different groups of patients and was sensitive to clinical change in patients' conditions. It proved to be a reliable and valid instrument for assessing the quality of life of patients with chronic diseases and their caregivers in China.

Caregivers↗

PubMed2003

The novel Rho GTPase-activating protein family protein, Rga8, provides a potential link between Cdc42/p21-activated kinase and Rho signaling pathways in the fission yeast, Schizosaccharomyces pombe.

The PAK family kinase, Shk1, is an essential regulator of polarized growth in the fission yeast, Schizosaccharomyces pombe. Here we describe the characterization of a novel member of the RhoGAP family, Rga8, identified from a two-hybrid screen for proteins that interact with the Shk1 kinase domain. Although deletion of the rga8 gene in wild type S. pombe cells results in no obvious phenotypic defects under normal growth conditions, it partially suppresses the cold-sensitive growth and morphological defects of S. pombe cells carrying a hypomorphic allele of the shk1 gene. By contrast, overexpression of rga8 is lethal to shk1-defective cells and causes morphological and cytokinesis defects in wild type S. pombe cells. Consistent with a role for Rga8 as a downstream target of Shk1, we show that the Rga8 protein is directly phosphorylated by Shk1 in vitro and phosphorylated in a Shk1-dependent fashion in S. pombe cells. Fluorescence photomicroscopy of the GFP-Rga8 fusion protein indicates that Rga8 is localized to the cell ends during interphase and to the septum-forming region during cytokinesis. In S. pombe cells carrying the orb2-34 allele of shk1, Rga8 exhibits a monopolar pattern of localization, providing evidence that Shk1 contributes to the regulation of Rga8 localization. Although molecular analyses suggest that Rga8 functions as a GAP for the S. pombe Rho1 GTPase, genetic experiments suggest that Rga8 and Rho1 have a positive functional interaction and that gain of Rho1 function, like gain of Rga8 function, is lethal to Shk1-defective cells. Our results suggest that Rga8 is a Shk1 substrate that negatively regulates Shk1-dependent growth control pathway(s) in S. pombe, potentially through interaction with the Rho1 GTPase.

Amino Acid Sequence↗

PubMed2002

Fixed ratio discrimination training increases in vivo striatal dopamine in neonatal 6-OHDA-lesioned rats.

Massed training in the conditional discrimination task, the fixed ratio discrimination (FRD) task led to elevated extracellular dopamine (DA) concentrations in the neonatal 6-hydroxydopamine (6-OHDA)-treated rat, a model of Lesch-Nyhan disease (LND). Rats neonatally treated with 6-OHDA or its vehicle were, as adults, implanted with microdialysis probes and assessed for basal pretraining concentrations of DA and its major metabolites. Subsequently, microdialysis samples were collected each day following three separate FRD training periods (trained group) or three separate periods of noncontingent food presentations (untrained group). The present study found that there were significant increases in extracellular DA in the caudate-putamen from basal pretraining concentrations in the repeated sample collections of trained 6-OHDA-lesioned animals but not in the samples of untrained 6-OHDA-lesioned animals. Consistent with previous studies [Brain Res. 508 (1990) 30.], there was an increase in the extracellular concentrations as compared to tissue concentrations of DA and 3,4-dihydroxyphenylacetic acid (DOPAC). Similar to our previous studies with long-term FRD training [Pharmacol. Biochem. Behav. 51 (1995) 861; Brain Res. 713 (1996) 246.], there was also an indication of an increase in cortical and striatal tissue concentration of DA in the trained 6-OHDA-lesioned animals as compared to the untrained 6-OHDA-lesioned animals. The elevations in striatal DA concentrations following operant performance in the present study illustrate how operant procedures of the behavior therapy used with individuals with LND and other mental retardation syndromes may interact with the modulation of dopaminergic function by the pharmaceutical application of DA antagonists to suppress aberrant behaviors.

Animals↗

PubMed2002

[Selective resection of the carotid artery for the treatment of carotid body tumor].

OBJECTIVE: Selecting carotid tumors and preventing the fatal bleeding of intraoperation. METHOD: The carotid compression test and inspection of angiography with transcranial Doppler sonography and keeping intraoperative awake after relieving pain anesthetization. RESULT: Ten cases of carotid artery were occluded for 2 hours within operation, and 4 carotids were resected and 6 carotid body tumor were peeled and their carotid were reserved. No neurological problems were encountered in the 10 patients for 5 years. CONCLUSION: Our experience proved that the carotid compression test and inspection of angiography with transcranial Doppler sonography and keeping intraoperative awake after relieving pain anesthetization can help to supervise the selective carotid resection.

Adult↗