Biomedical subjects

Yi Shi

Publications and source records attributed to Yi Shi.

At least 19 recordsLinked to original sources

PubMed2026

Molecular differences between poorly and well/moderately differentiated lung adenocarcinoma and their clinical implications.

BACKGROUND: Diagnostic and therapeutic techniques for lung adenocarcinoma (LUAD) have advanced rapidly. However, the morphology-based assessment of tumor differentiation commonly used in clinical practice has several limitations, including strong subjectivity, inability to reflect tumor heterogeneity, and limited prognostic predictive value. This study aimed to identify key genetic mutations associated with tumor differentiation features and explored their potential clinical impact of these molecular features on tumor prognosis and therapeutic response. METHODS: In this study, 196 LUAD tissue samples collected from Fujian Cancer Hospital between 2021 and 2023 were analyzed using integrated high-throughput sequencing and comprehensive bioinformatics approaches. Molecular differences between poorly differentiated tumors and moderately/well-differentiated tumors were characterized. The effects of these molecular alterations on tumor behavior and therapeutic response were examined, with the aim of exploring biomarkers associated with poor prognosis and treatment in LUAD. RESULTS: Our findings showed a significant quantitative difference in tumor mutation burden, EGFR co-mutations, patterns of co-occurrence resulting in distinct clinical outcomes. Among these alterations, mutations in LRP1B and TP53, as well as EGFR amplification, MET amplification, JAK2 deletion and CDKN2B deletion were significantly enriched in the poorly differentiated group, whereas EGFR mutations were significantly enriched in the moderately/well-differentiated group. We also identified MET amplification and LRP1B mutation as independent poor prognostic factors in LUAD. Moreover, a subset of poorly differentiated group exhibited DNA double-strand breaks possibly due to homologous recombination deficiency (HRD), along with frequent alterations of immune evasion-related genes. CONCLUSIONS: These findings provide novel insights into the molecular basis of LUAD and the development of novel targeted differentiation-related therapies and precision genome-guided treatments.

Lung adenocarcinoma (LUAD)↗

PubMed2026

Chromatin Remodeling Subunit ARID1A Negatively Regulates the Malignant Progression of Gastrointestinal Stromal Tumors by Targeting the MEMO1 Promoter.

Gastrointestinal stromal tumors (GISTs) are the most common sarcomas of the alimentary tract and are primarily characterized by malignant progression, a major cause of mortality. AT-rich interaction domain 1A (ARID1A), a core component of the chromatin-remodeling SWI/SNF complex, has been found to correlate with GIST tumor grade, although the underlying mechanism remains unclear. Its frequent inactivation across diverse cancer types reveals pleiotropic roles that intersect multiple hallmarks of cancer. In this study, we aimed to investigate the potential relationship between ARID1A and malignant progression in GISTs, as well as the underlying mechanism. Western blotting, real-time polymerase chain reaction, and immunohistochemistry were used to assess ARID1A expression in GIST tissues. Cell Counting Kit-8 (CCK-8) assays were performed to evaluate cell proliferation. Wound-healing and Transwell assays were conducted to assess cell migration and invasion. Flow cytometry was used to analyze apoptosis and cell cycle distribution. Label-free quantitative proteomics and chromatin immunoprecipitation sequencing (ChIP-seq) were employed to identify top candidate downstream targets of ARID1A. ARID1A expression was decreased in high-risk GIST tissues. Furthermore, ARID1A knockdown in GIST cells promoted proliferation and metastasis both in vitro and in vivo, and led to reduced apoptosis and impaired cell cycle arrest. We further demonstrated that ARID1A suppresses GIST proliferation and metastasis by inhibiting MEMO1 expression and inactivating the ERK1/2 signaling pathway. Notably, this regulatory axis was observed in KIT-null GIST cells, indicating that the ARID1A-MEMO1 pathway may function independently of canonical KIT signaling. Thus, ARID1A inhibits malignant progression in GISTs, providing new insights into its role in the prevention and treatment of human GISTs and suggesting its potential as a biomarker of malignant progression in GISTs.

Humans↗

PubMed2025

One thousand SARS-CoV-2 antibody structures reveal convergent binding and near-universal immune escape.

Understanding antibody recognition and adaptation to viral evolution is central to vaccine and therapeutic development. Over 1,100 SARS-CoV-2 antibody structures have been resolved, marking the largest structural biology effort for a single pathogen. We present a comprehensive analysis of this landmark dataset to investigate the principles of antibody recognition and immune escape. Human immunoglobulins and camelid single-chain antibodies dominate, collectively mapping 99% of the receptor-binding domain. Despite remarkable sequence and conformational diversity, antibodies exhibit convergence in their paratope structures, revealing evolutionary constraints in epitope selection. Analyses reveal near-universal immune escape of antibodies, including all clinical monoclonals, by advanced variants such as KP3.1.1. On average, over one-third of antibody epitope residues are mutated. These findings support pervasive immune escape, underscoring the need to effectively leverage multi-epitope-targeting strategies to achieve durable immunity. To support community accessibility, we developed an interactive web server for visualization and analysis of antibody-antigen complexes and mutational data.

SARS-CoV-2↗

PubMed2024

NS2 induces an influenza A RNA polymerase hexamer and acts as a transcription to replication switch.

Genome transcription and replication of influenza A virus (FluA), catalyzed by viral RNA polymerase (FluAPol), are delicately controlled across the virus life cycle. A switch from transcription to replication occurring at later stage of an infection is critical for progeny virion production and viral non-structural protein NS2 has been implicated in regulating the switch. However, the underlying regulatory mechanisms and the structure of NS2 remained elusive for years. Here, we determine the cryo-EM structure of the FluAPol-NS2 complex at ~3.0 Å resolution. Surprisingly, three domain-swapped NS2 dimers arrange three symmetrical FluPol dimers into a highly ordered barrel-like hexamer. Further structural and functional analyses demonstrate that NS2 binding not only hampers the interaction between FluAPol and the Pol II CTD because of steric conflicts, but also impairs FluAPol transcriptase activity by stalling it in the replicase conformation. Moreover, this is the first visualization of the full-length NS2 structure. Our findings uncover key molecular mechanisms of the FluA transcription-replication switch and have implications for the development of antivirals.

Viral Nonstructural Proteins↗

PubMed2007

[Association between cluster of differentiation 14 polymorphism and susceptibility of infection].

OBJECTIVE: To investigate the association between the single nucleotide polymorphisms (SNPs) of cluster of differentiation 14 (CD14) and susceptibility in patients with sepsis. METHODS: One hundred and twelve patients with sepsis admitted to the intensive care unit (ICU) from December 2004 to March 2006 were enrolled for study. Another 100 healthy volunteer donors were chosen serving as the normal control group. Genotypes and alleles of CD14-159 C/T, CD14-260 C/T were determined in patients and healthy controls by means of restriction fragment length polymorphism (RFLP) analysis of polymerase chain reaction (PCR) products. Distributional differences of genotypes and alleles between patients and healthy controls were analyzed. The sepsis patients were divided into survivor group and non-survivor group depending on survival for 28 days. Distributional differences of genotypes and alleles between survivor group and non-survivor group were determined. RESULTS: The rates of CD14-159 C/T genotypes and T-alleles in patients with sepsis were significantly higher than those of healthy volunteers (P=0.005 and P=0.000). There were no significant differences in the rates of CD14-260 C/T genotypes and T-alleles in two groups (P=0.912 and P=0.706). The rates of CD14 -159 C/T genotypes and T-alleles in non-survivors were significantly higher than those of survivors (both P=0.000). There were no significant differences in the rates of CD14-260 C/T genotypes and T-alleles in two groups (P=0.643 and P=0.890). CONCLUSION: The differences of CD14-159 C/T genotypes of SNPs may be associated with the higher risk of susceptibility and mortality of sepsis.

Adolescent↗

PubMed2006

Potentiation of the immune response to non-adsorbed antigens by aluminum-containing adjuvants.

The degree of antigen adsorption by aluminum-containing adjuvants is considered an important characteristic of vaccines that is related to immunopotentiation by the adjuvant. This study examined immunopotentiation by aluminum phosphate adjuvant in three model vaccines in which the antigen was not adsorbed in the vaccine formulation nor when mixed in vitro with interstitial fluid. In the first model vaccine, aluminum phosphate adjuvant was pre-treated with 0.5 M KH2PO4 to minimize the adsorption of dephosphorylated alpha casein. The second model vaccine was composed of aluminum phosphate adjuvant and ovalbumin that was dephosphorylated by treatment with potato acid phosphatase. The third model vaccine consisted of aluminum phosphate adjuvant and lysozyme (LYS). In order to prevent adsorption of lysozyme, the aluminum phosphate adjuvant was pre-treated with fibrinogen, a protein present in interstitial fluid that binds strongly to aluminum phosphate adjuvant. Immunopotentiation was evaluated by measuring antibody production in mice. It was found that all three model vaccines induced antibody titers that were statistically higher than induced by a solution of antigen without adjuvant and similar to vaccines in which the antigens were adsorbed by aluminum phosphate adjuvant. Confocal microscopy experiments suggested that the antigens used in these experiments, even though not adsorbed to the aluminum phosphate adjuvant, were trapped in void spaces within the adjuvant aggregates, resulting in uptake of antigen by dendritic cells.

Adjuvants, Immunologic↗

PubMed2006

Role of lipoprotein-associated phospholipase A2 in leukocyte activation and inflammatory responses.

BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an emerging cardiovascular risk marker. To explore the biologic role of Lp-PLA2 in atherosclerosis, we examined its expression and contribution to leukocyte activation under proatherogenic conditions. METHODS AND RESULTS: Following the induction of diabetes and hypercholesterolemia in a porcine model, a rapid increase in plasma Lp-PLA2 activity was observed at 1 month. This was accompanied by upregulated Lp-PLA2 mRNA expression by peripheral blood mononuclear cells (PBMC) at 3 months, and elevated Lp-PLA2 mRNA expression in coronary arteries at 6 months. These changes were paralleled by increased inflammatory responses by circulating PBMC (ICAM-1, IL-6), in coronary tissues (ICAM-1, VCAM-1), and the subsequent accumulation of inflammatory cells. In human PBMC, proinflammatory mediators augmented the synthesis and release of functional Lp-PLA2. Furthermore, lysophosphatidylcholine (lysoPC), a product of Lp-PLA2 activity, induced an increase in several inflammatory cytokines (IL-1beta, IL-6, TNF-alpha) in a concentration-dependent manner. In contrast, Lp-PLA2 inhibition (SB677116; 1 microM) abrogated the inflammatory response elicited by oxidized LDL. CONCLUSIONS: In an experimental model of diabetes and hypercholesterolemia, leukocyte activation was associated with augmented Lp-PLA2 expression. In vitro, Lp-PLA2 activity mediated leukocyte activation and inflammatory responses, whereas Lp-PLA2 inhibition abolished inflammatory responses induced by oxidized LDL. Collectively, these observations support a proatherogenic role for Lp-PLA2.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

PubMed2006

Augmented endothelium-derived hyperpolarizing factor-mediated relaxations attenuate endothelial dysfunction in femoral and mesenteric, but not in carotid arteries from type I diabetic rats.

Individual vascular beds exhibit differences in vascular reactivity. The present study investigates the effects of streptozotocin-induced type I diabetes on endothelium-dependent responses of rat carotid, femoral, and mesenteric arteries. Rings with and without endothelium, suspended in organ chambers for isometric tension recording, were contracted with phenylephrine and exposed to increasing concentrations of acetylcholine. In carotid and femoral arteries, acetylcholine produced concentration- and endothelium-dependent relaxations that were abolished by Nomega-nitro-L-arginine methyl ester (L-NAME; specific nitric-oxide synthase inhibitor) and were impaired slightly in preparations from streptozotocin-treated rats (STZ-rats). This impairment could be prevented by L-arginine. In femoral arteries incubated with L-NAME, acetylcholine caused endothelium-dependent contractions that were abolished by 3-[(6-amino-(4-chlorobenzensulfonyl)-2-methyl-5,6,7,8-tetrahydronapht]-1-yl) propionic acid (S18886) (antagonist of thromboxane A2/prostaglandins H2-receptors) and reversed to relaxation by indomethacin (inhibitor of cyclooxygenase). The latter relaxation was inhibited by charybdotoxin plus apamin, suggesting a role of endothelium-dependent hyperpolarizing factor (EDHF). This EDHF-mediated component was augmented slightly in arteries from STZ-rats. In mesenteric arteries, relaxations to acetylcholine were only partially inhibited by L-NAME, and the L-NAME-resistant component was abolished by charybdotoxin plus apamin. In the mesenteric arteries from STZ-rats, L-NAME-sensitive relaxations to acetylcholine were reduced and the EDHF-component was augmented. These findings demonstrate a marked heterogeneity in endothelium-dependent responses in rat arteries and their differential adaptation in the course of type I diabetes. In particular, the EDHF-mediated component not only compensates for the reduced bioavailability of nitric oxide in the femoral and mesenteric artery but also counteracts the augmented endothelium-dependent contractions in the former.

Acetylcholine↗

PubMed2006

Inhibition of connective tissue growth factor by siRNA prevents liver fibrosis in rats.

BACKGROUND: Connective tissue growth factor (CTGF) is a highly profibrogenic molecule implicated in hepatic fibrogenesis. Small interfering RNA (siRNA) is an effective tool to silence gene expression post-transcriptionally. Therefore, we conducted an investigation to determine if intraportal vein siRNA injection targeting CTGF inhibits CTGF expression on rat liver in vivo and furthermore whether it protects the liver from liver fibrosis. METHODS: Some rats received carbon tetrachloride (CCl4) by subcutaneous injections every three days for six consecutive weeks, and meantime they also obtained either siRNA (0.1 mg/kg) targeting CTGF, saline or a control siRNA by intraportal vein injection to rats' liver at the same pattern. Other rats received CCl4 by subcutaneous injection for 2 weeks, followed by CCl4 and CTGF siRNA intraportal vein injection for four more weeks. RESULTS: Intraportal vein injection of CTGF siRNA specifically reduced the expression of CTGF protein in rat liver, and these effects were maintained for 3 days. Six weeks after CCl4 injection, prominent upregulations were observed in the gene expressions of CTGF, type I, III collagen, laminin, tissue inhibitor metal proteinase-1 (TIMP-1) and transforming growth factor-beta1 (TGF-beta1) in saline or control siRNA-treated rats livers. Administrating CTGF siRNA for 4 or 6 weeks, by contrast, markedly attenuated the induction of CTGF, type I, III collagen, laminin, TIMP-1 and TGF-beta1 genes, whereas Smad2, 7 gene expression was not affected. The number of active hepatic stellate cells (HSCs) determined by the expression of alpha-smooth muscle actin was also significantly decreased. The CTGF siRNA treatment markedly reduced serum procollagen type III, hepatic hydroxyproline and liver fibrosis staging. CONCLUSIONS: Silencing CTGF expression with siRNA demonstrates therapeutic potential to prevent liver fibrosis by inhibiting HSC activation with consequent extracellular matrix accumulation and the upregulation of TGF-beta1 gene expression.

Animals↗

PubMed2006

Modulation of collagen synthesis in keloid fibroblasts by silencing Smad2 with siRNA.

BACKGROUND: Keloids represent a dysregulated response to cutaneous wounding that results in an excessive deposition of extracellular matrix, especially types I and III collagen. Transforming growth factor (TGF)-beta plays a central role in the pathogenesis of fibrosis by inducing and sustaining activation of keloid fibroblast. However, the underlying mechanisms are poorly understood. In this study, the authors examined the function of Smad2, a recently characterized intracellular effector of TGF-beta signaling, in keloid fibroblasts using small interfering RNA (siRNA). METHODS: Three pairs of siRNA duplexes targeting human Smad2 were designed; the most efficient one was selected and used for further research. Keloid fibroblasts were treated with or without Smad2 siRNA, and the expression levels of related genes were examined by reverse-transcriptase polymerase chain reaction and immunofluorescence. RESULTS: The down-regulation of Smad2 by siRNA led to a significant decrease in mRNA levels of Smad2 in both a dose-dependent and time-dependent manner. The knockdown of Smad2 expression in protein level was confirmed using immunofluorescence. The mRNA levels of types I and III procollagen were also significantly and uniquely decreased following the reduction of Smad2 by siRNA. CONCLUSIONS: The results indicate that Smad2 plays an important role in TGF-beta-induced fibrosis in keloids. Down-regulation of Smad2 expression in keloid fibroblasts can significantly decrease procollagen gene expression. Also, siRNA targeting Smad2 was an efficient reagent with which to reduce extracellular matrix deposition and attenuate process of fibrosis. It could be a new, promising therapeutic approach for improving skin wound healing and inhibiting progression of fibrotic conditions by interrupting the TGF-beta signaling pathway.

Adult↗

PubMed2006

Incidence of positive C4d deposition in long-term survival cases over 10 yr after renal transplantation.

BACKGROUND: The incidence of positive C4d deposition in peritubular capillaries (PTC) in long-term survival cases remains controversial. Some incidences of positive C4d deposition in PTC in cases of long-term survival less than 10 yr have been reported. We retrospectively examined the incidence of positive C4d deposition in long-term survival cases over 10 yr after renal transplantation and the histological and clinical characteristics of the positive C4d staining cases. METHODS: We examined 14 protocol biopsy cases performed at Osaka University Hospital between March 2004 and March 2005. The average interval between the operation and the day of biopsy was 15.4 yr. Histological diagnosis was made in accordance with the Banff 97 classification. Paraffin-embedded tissue was stained with polyclonal anti-C4d antibody. Detection of donor-specific antibody (DSA) was determined by flow cytometric assay. The cases were divided according to C4d positivity. RESULTS: Three of 14 cases (21.4%) were C4d positive and belonged to the C4d+/DSA+ group, while 11 cases were of the C4d-/DSA- group. There were no significant differences between the two groups in serum creatinine (sCr) or proteinuria at the time of biopsy. A trend towards decreasing rate of the inverse of sCr (1/sCr) in the C4d+/DSA+ group was noted. In the C4d+/DSA+ group, three transplant glomerulopathy (TGP) were identified. On the other hand, TGP were identified in six of 11 cases of the C4d-/DSA- group. We investigated the relevance of typical chronic rejection (CR) features and the positivity of C4d. No significant differences were observed between the CR features and C4d depositions in PTC (p = 0.26). CONCLUSION: In long-term survival cases with positive C4d, a trend towards decreasing rate of 1/sCr was revealed, but their histological characteristic features was not recognized.

Adult↗

PubMed2006

ABO-incompatible kidney transplantation with anti-CD20 monoclonal antibodies, intravenous immunoglobulin and plasmapheresis without splenectomy: a case report.

A 24-yr-old man was admitted to our hospital for ABO-incompatible kidney transplantation. His blood type was O, and the donor's (his father's) blood type was B. The recipient had pancytopenia, splenomegaly, splenorenal shunts and esophageal varices due to congenital hepatic fibrosis. Therefore, if splenorectomy was performed, the blood pressure of the portal vein and the growth of esophageal varices were predicted. Eventually, in return for splenectomy, anti-CD20 monoclonal antibodies (rituximab), intravenous immunoglobulin and plasmapheresis was performed for additional immunosuppression. Because of progression of pancytopenia, we had to decrease the dose of mycophenolate mofetil and gave up on using deoxyspagalin. Nevertheless the serum creatinine level decreased and remained in the 1.6 to 1.8 mg/dl range.

ABO Blood-Group System↗

PubMed2006

A preoperative and intraoperative predictive model of prolonged intensive care unit stay for valvular surgery.

BACKGROUND AND AIM OF THE STUDY: In developing countries, the costs of intensive care unit (ICU) stay are very high for patients after valve surgery. In addition, patients with a prolonged ICU stay have a poor prognosis compared to those with a short ICU stay. The study aim was to develop a specific risk model and to use a logistic EuroSCORE model to predict prolonged ICU stay after valve surgery. METHODS: A total of 507 consecutive patients undergoing valve surgery were studied using univariate and multivariate analyses. Prolonged ICU stay was defined as five days or more. Stepwise logistic regression analysis was used to identify the risk factors for prolonged ICU stay. These variables were then used to calculate a prognostic score (S) and a predicted probability (P) for prolonged ICU stay. A receiver operating characteristic (ROC) curve was calculated to measure the prognostic value of the new risk model and logistic EuroSCORE model. Sensitivity and specificity analysis were used for evaluation. RESULTS: Multivariate logistic regression analysis showed that age > or = 65 years, left ventricular ejection fraction (LVEF) < or = 50%, cardiothoracic ratio (CTR) > or = 0.68, previous cardiac surgery, maximal voluntary ventilation (MVV) observed/predicted < 71% and repeat cardiopulmonary bypass (CPB) during surgery were risk factors. Mitral valve surgery reduced the risk of prolonged ICU stay. Observed probabilities compared well with predicted probabilities. The ROC curve produced an area under the curve (AUC) value of 0.81 for prolonged ICU stay. Based on predicted probability, patients were classified as low-risk (0 < or = P < 10%), intermediate-risk (10% < or = P < 20%), high-risk (20% < or = P < 40%) and very high-risk (> or = 40%) groups. A P-value > or = 40% was used as a cut-off point for the prognostic test. The specificity of this test was 97%, sensitivity 32%, positive predictive value 62%, negative predictive value 89%, positive likelihood ratio 10.67, and negative likelihood ratio 0.70. The ROC curve of a logistic EuroSCORE model gave an AUC value of 0.66 for prolonged ICU stay. CONCLUSION: The study results showed that individual patients undergoing valve surgery could be stratified according to their risk factors for prolonged ICU stay. High-risk patients may require more careful preoperative and postoperative management to reduce postoperative mortality, morbidity, the length of ICU stay, and therefore the cost of valve surgery.

Cardiac Surgical Procedures↗

PubMed2006

[Effects of P application on P concentrations in paddy soil and its surface water: a simulation test].

An anaerobic incubation test was conducted to study the effects of different P application rate on the P concentrations in paddy soil and its surface water. The results showed that soil available P (Olsen-P) decreased rapidly at the beginning, but approached to stable after 60 days of P application. Both Olsen-P and residual P increased with increasing P application rate, and Olsen-P had a positive correlation with P application rate, suggesting that the test soil had a strong P adsorption capacity. After P application, the total P (TP) in soil surface water increased rapidly, and then decreased slowly, showing that there was a P exchange between soil and its surface water. After 120 days of P application, there was an exponential relationship between soil surface water TP and P application. The TP in soil surface water increased rapidly when the P application rate was 400 - 800 kg x hm (-2) , and easy to be lost when the P application rate was higher than 800 kg x hm(-2). The simulation with split line model on the relationship between soil Olsen-P and soil surface water TP showed that the change point of soil Olsen-P, which induced a sharp increase of soil surface water TP concentration, was 82. 7 mg x kg( -l) , corresponding to a P application rate being about 712 x kg hm(-2). Soil Olsen-P could be a good indicator in forecasting the P loss from soil surface water.

Fertilizers↗

PubMed2005

[Reduction aortoplasty for dilatation of the ascending aorta in patients with aortic valve disease].

OBJECTIVE: To evaluate the effect of reduction aortoplasty for dilatation of the ascending aorta in patients with aortic valve disease. METHODS: Between February 1998 and May 2004, 23 patients with aortic valve disease and dilatation of the ascending aorta underwent reduction aortoplasty in combination with aortic valve replacement. The diameter of the ascending aorta was measured before and early after surgery and then later between 4 and 78 months [mean (36 +/- 25) months] postoperatively using echocardiography. RESULTS: The reduction aortoplasty decreased the diameter of the aorta from (4.8 +/- 0.5) cm preoperatively to (3.6 +/- 0.4) cm early after surgery (P < 0.01). During follow-up, the diameter of aorta increased from (3.6 +/- 0.4) cm early after surgery to (3.7 +/- 0.4) cm after a mean follow-up of (36 +/- 25) months (P < 0.05). CONCLUSION: Reduction aortoplasty shows good mid-term results in patients with aortic valve disease and dilatation of the ascending aorta. Long-term results need to be followed up.

Adult↗

PubMed2005

A novel immunosuppressant FTY720 ameliorates proteinuria and alterations of intrarenal adrenomedullin in rats with autoimmune glomerulonephritis.

FTY720 has been originally developed as a new immunosuppressive agent, which prolongs graft survival in organ transplantation. Adrenomedullin (AM) participates in the regulation of sodium homeostasis and has renoprotective effects. The possible involvement of renal AM in the pathophysiology of glomerulonephritis (GN) and the effect of FTY720 has been evaluated in rats. HgCl2 (1 mg/kg body weight) was inoculated subcutaneously 3 times/week for a total of 2 weeks. FTY720 (3 or 10 mg/kg) was inoculated subcutaneously daily. The proteinuria, urinary N-acetyl-beta-D-glucosaminidase (NAG) excretion and serum total cholesterol levels were increased and serum albumin level was reduced in rats with HgCl2-induced GN compared with controls. FTY720 reduced proteinuria (3 mg/kg: -25%; 10 mg/kg: -41%), urinary NAG excretion (-11%; -52%) and total cholesterol level (-21%; -55%) in a dose-dependent manner. Renal AM level and its mRNA expression were increased in rats with GN compared with controls (Peptide Cortex: +69%; Medulla: +82%; mRNA Cortex: +25%). Interestingly, FTY720 additionally increased these levels (Peptide Cortex: +38%; Medulla: +39%; mRNA Cortex: +20%). Renal AM levels correlated with urinary NAG excretion and creatinine clearance. These results suggest that FTY720 suppresses the renal damage in rats with GN and renal AM may participate in the pathophysiology of GN and the renoprotective effects of FTY720.

Adrenomedullin↗

PubMed2005

Antisense downregulation of SARS-CoV gene expression in Vero E6 cells.

BACKGROUND: Severe acute respiratory syndrome (SARS) is caused by a novel coronavirus (SARS-CoV). It is an enveloped, single-stranded, plus-sense RNA virus with a genome of approximately 30 kb. The structural proteins E, M and N of SARS-CoV play important roles during host cell entry and viral morphogenesis and release. Therefore, we have studied whether expression of these structural proteins can be down-regulated using an antisense technique. METHODS: Vero E6 cells were transfected with plasmid constructs containing exons of the SARS-CoV structural protein E, M or N genes or their exons in frame with the reporter protein EGFP. The transfected cell cultures were treated with antisense phosphorothioated oligonucleotides (antisense PS-ODN, 20mer) or a control oligonucleotide by addition to the culture medium. RESULTS: Among a total of 26 antisense PS-ODNs targeting E, M and N genes, we obtained six antisense PS-ODNs which could sequence-specifically reduce target genes expression by over 90% at the concentration of 50 microM in the cell culture medium tested by RT-PCR. The antisense effect was further proved by down-regulating the expression of the fusion proteins containing the structural proteins E, M or N in frame with the reporter protein EGFP. In Vero E6 cells, the antisense effect was dependent on the concentrations of the antisense PS-ODNs in a range of 0-10 microM or 0-30 microM. CONCLUSIONS: The antisense PS-ODNs are effective in downregulation of SARS. The findings indicate that antisense knockdown of SARS could be a useful strategy for treatment of SARS, and could also be suitable for studies of the pathological function of SARS genes in a cellular model system.

Animals↗

PubMed2005

Respective and interactive effects of doubled CO2 and O3 concentration on membrane lipid peroxidation and antioxidative ability of soybean.

Effects of doubled CO2 and O3 concentration on Soybean were studied in open-top chambers (OTC). Under doubled CO2 concentration, grain yield and biomass increased, the SOD activity, vitamin C (Vc) and carotenoid (Car) content also increased; Superoxide (O2-*) generating rate decreased, relative conductivity and malondialdehyde (MDA) content significantly declined. But under doubled O3 concentration, the SOD activity, Vc and Car contents declined, resulting in imbalance of activated-oxygen production, enhanced O2-* generating rate and accelerated process of lipid peroxidation and increase in MDA content and ion leakage of leaves. The final result was decreased grain yield and plant biomass. Interactive effects of doubled CO2 and O3 concentrations on soybean were mostly counteractive. However, the beneficial effects of concentration-doubled CO2 more than compensate the negative effects imposed by doubled O3, and the latter in its turn partly counteracted the positive effects of the former.

Antioxidants↗