Biomedical subjects

Haibo Zhang

Publications and source records attributed to Haibo Zhang.

At least 19 recordsLinked to original sources

PubMed2026

Respiratory viral infections prime accelerated lung cancer growth.

The COVID-19 pandemic has highlighted the long-term consequences of viral pneumonia, yet its impact on cancer development remains unclear. Here, we show that patients previously hospitalized with severe COVID-19 have an increased risk of subsequent lung cancer. Across multiple murine models, severe respiratory viral infections accelerated lung cancer growth, whereas vaccination mitigated infection-enhanced tumor progression. Mechanistically, prior viral pneumonia reprogrammed the lung into a pro-tumor microenvironment marked by the sustained accumulation of tumor-associated neutrophils and heightened immunosuppression. We observed persistent chromatin remodeling at key cytokine loci in immune and structural cells, linking inflammatory memory to tumor-promoting signals. Therapeutically, combined blockade of neutrophil recruitment and programmed death-ligand 1 (PD-L1) restored CD8+ T cell function and suppressed tumor growth. Together, these findings establish a causal link between prior viral pneumonia and lung tumorigenesis, underscoring the need for enhanced surveillance and targeted interventions to reduce post-COVID cancer risk.

Animals↗

PubMed2007

Event-specific quantitative detection of nine genetically modified maizes using one novel standard reference molecule.

With the development of genetically modified organism (GMO) detection techniques, the Polymerase Chain Reaction (PCR) technique has been the mainstay for GMO detection, and real-time PCR is the most effective and important method for GMO quantification. An event-specific detection strategy based on the unique and specific integration junction sequences between the host plant genome DNA and the integrated gene is being developed for its high specificity. This study establishes the event-specific detection methods for TC1507 and CBH351 maizes. In addition, the event-specific TaqMan real-time PCR detection methods for another seven GM maize events (Bt11, Bt176, GA21, MON810, MON863, NK603, and T25) were systematically optimized and developed. In these PCR assays, the fluorescent quencher, TAMRA, was dyed on the T-base of the probe at the internal position to improve the intensity of the fluorescent signal. To overcome the difficulties in obtaining the certified reference materials of these GM maizes, one novel standard reference molecule containing all nine specific integration junction sequences of these GM maizes and the maize endogenous reference gene, zSSIIb, was constructed and used for quantitative analysis. The limits of detection of these methods were 20 copies for these different GM maizes, the limits of quantitation were about 20 copies, and the dynamic ranges for quantification were from 0.05 to 100% in 100 ng of DNA template. Furthermore, nine groups of the mixed maize samples of these nine GM maize events were quantitatively analyzed to evaluate the accuracy and precision. The accuracy expressed as bias varied from 0.67 to 28.00% for the nine tested groups of GM maize samples, and the precision expressed as relative standard deviations was from 0.83 to 26.20%. All of these indicated that the established event-specific real-time PCR detection systems and the reference molecule in this study are suitable for the identification and quantification of these GM maizes.

Base Sequence↗

PubMed2007

Role of human neutrophil peptides in the initial interaction between lung epithelial cells and CD4+ lymphocytes.

Human neutrophil peptides (HNP) exert immune-modulating effects. We hypothesized that HNP link innate and adaptive immunity through activation of costimulatory molecules. Human lung epithelial cells and CD4+ lymphocytes were treated with HNP separately or in coculture. Stimulation with HNP induced an increase in cell surface expression of CD54 (ICAM-1), CD80, and CD86 on lung epithelial cells and the corresponding major ligands, CD11a (LFA-1), CD152 (CTLA-4), and CD28 on CD4+ lymphocytes. There was an increased nuclear expression of the transcription factor p53 in human alveolar A549 cells and an elevated NF-kappaB (p50) and a degradation of I-kappaB protein in CD4+ lymphocytes following HNP stimulation. HNP enhanced the interaction between A549 cells and CD4+ lymphocytes by increasing cell adhesion and release of IFN-gamma, IL-2, and IL-8. This was attenuated by using an alpha1-proteinase inhibitor to neutralize HNP. We conclude that HNP play an important role in linking innate to acquired immunity by activation of costimulatory molecules in lung epithelial cells and CD4+ lymphocytes.

Anti-Infective Agents↗

PubMed2006

Event-specific qualitative and quantitative polymerase chain reaction analysis for genetically modified canola T45.

Polymerase chain reaction (PCR) methods have been the main technical support for the detection of genetically modified organisms (GMOs). To date, GMO-specific PCR detection strategies have been developed basically at four different levels, such as screening-, gene-, construct-, and event-specific detection methods. Event-specific PCR detection method is the primary trend in GMO detection because of its high specificity based on the flanking sequence of exogenous integrant. GM canola, event T45, with tolerance to glufosinate ammonium is one of the commercial genetically modified (GM) canola events approved in China. In this study, the 5'-integration junction sequence between host plant DNA and the integrated gene construct of T45 canola was cloned and revealed by means of TAIL-PCR. Specific PCR primers and TaqMan probes were designed based upon the revealed sequence, and qualitative and quantitative TaqMan real-time PCR detection assays employing these primers and probe were developed. In qualitative PCR, the limit of detection (LOD) was 0.1% for T45 canola in 100 ng of genomic DNA. The quantitative PCR assay showed limits of detection and quantification (LOD and LOQ) of 5 and 50 haploid genome copies, respectively. In addition, three mixed canola samples with known GM contents were detected employing the developed real-time PCR assay, and expected results were obtained. These results indicated that the developed event-specific PCR methods can be used for identification and quantification of T45 canola and its derivates.

Base Sequence↗

PubMed2006

Resilience of Rhodobacter sphaeroides cytochrome bc1 to heme c1 ligation changes.

Typically, c hemes are bound to the protein through two thioether bonds to cysteines and two axial ligands to the heme iron. In high-potential class I c-type cytochromes, these axial ligands are commonly His-Met. A change in this methionine axial ligand is often correlated with a dramatic drop in the heme redox potential and loss of function. Here we describe a bacterial cytochrome c with an unusual tolerance to the alternations in the heme ligation pattern. Substitution of the heme ligating methionine (M185) in cytochrome c1 of the Rhodobacter sphaeroides cytochrome bc1 complex with Lys and Leu lowers the redox midpoint potential but not enough to prevent physiologically competent electron transfer in these fully functional variants. Only when Met-185 is replaced with His is the drop in the redox potential sufficiently large to cause cytochrome bc1 electron transfer chain failure. Functional mutants preserve the structural integrity of the heme crevice: only the nonfunctional His variant allows carbon monoxide to bind to reduced heme, indicating a significant opening of the heme environment. This range of cytochrome c1 ligand mutants exposes both the relative resilience to sixth axial ligand change and the ultimate thermodynamic limits of operation of the cofactor chains in cytochrome bc1.

Electron Transport Complex III↗

PubMed2006

Role of the PEWY glutamate in hydroquinone-quinone oxidation-reduction catalysis in the Qo Site of cytochrome bc1.

The glutamic acid residue of the conserved PEWY motif of the Q(o) site of cytochrome bc(1) is widely discussed as central to reversible Q(o) site catalysis of two-electron, two-proton hydroquinone-quinone oxidation-reduction. Extensive mutation of this glutamate (E295) to A, V, F, H, K, and Q in purple photosynthetic Rhodobacter capsulatus results in hydroquinone oxidation rates that are between 5 and 50-fold slower than that in the wild type. However, the mutants show little or no detectable effects on hydroquinone or quinone exchange and binding at the Q(o) site nor on subsequent Q(o) site-mediated redox equilibria in the c-chain and b-chain from pH 5-10. Lack of effects of mutations on the E(m)/pH plots rules out involvement of E295 in the strong electron-proton coupling evident in either the FeS center or heme b(L). These detailed equilibrium and kinetic analyses demonstrate that E295 is not irreplaceable in the Q(o) site catalytic mechanism. Rather, E295 and several other Q(o) site residues that can also be widely varied and still support hydroquinone oxidation illustrate the considerable resilience of Q(o) site activity to mutational change in Q(o) site environs. Residues and water molecules appear to cooperate in providing a physical and chemical environment supporting hydroquinone oxidation rates comparable to those seen in nonprotein aqueous environments at electrodes. We suggest that residues at the Q(o) site (and, possibly, other respiratory and photosynthetic quinone and oxygen binding sites) are a product of natural selection primarily acting not to lower catalytic barriers according to the traditional view of enzymatic catalysis but rather to develop specificity by raising barriers in defense of semiquinone loss or energy wasting short-circuit reactions.

Binding Sites↗

PubMed2006

Ischemia and reperfusion increases susceptibility to ventilator-induced lung injury in rats.

OBJECTIVES: Hemorrhagic shock followed by resuscitation (HSR) commonly triggers an inflammatory response that leads to acute respiratory distress syndrome. HYPOTHESIS: HSR exacerbates mechanical stress-induced lung injury by rendering the lung more susceptible to ventilator-induced lung injury. METHODS: Rats were subjected to HSR, and were randomized into an HSR + high tidal volume and zero positive end-expiratory pressure (PEEP) or a HSR + low tidal volume with 5 cm H(2)O PEEP. A sham-operated rat + high tidal volume and zero PEEP served as a control. RESULTS: HSR increased susceptibility to ventilator-induced lung injury as evidenced by an increase in lung elastance and the wet/dry ratio and a reduction in Pa(O(2)) as compared with the other groups. The lung injury observed in the HSR + high tidal volume group was associated with a higher level of interleukin 6 in the lung and blood, increased epithelial cell apoptosis in the kidney and small intestine villi, and a tendency toward high levels of alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and creatinine in plasma. CONCLUSIONS: HSR priming renders the lung and kidney more susceptible to mechanical ventilation-induced organ injury.

Alanine Transaminase↗

PubMed2006

Acute phase response in zebrafish upon Aeromonas salmonicida and Staphylococcus aureus infection: striking similarities and obvious differences with mammals.

Zebrafish has emerged as a valuable model for immunological studies. However, little is known about the overall picture of its immune response to infectious pathogens. Here we present the first systematic study of its immune response to Aeromonas salmonicida and Staphylococcus aureus, a Gram-negative and a Gram-positive bacteria, respectively. Genes induced upon infection were identified with suppression subtractive hybridization, with many of them encoding acute phase proteins (APPs). When compared with mammals, striking similarities and obvious differences have been observed. Both similar APPs (SAA, hepcidin and haptoglobin, etc.) and a similar system for the induction of APPs (which involves the TLRs, pro-inflammatory cytokines and C/EBPs) were identified, implying evolutionary conserved mechanisms among fish and mammals. Some novel APPs were also discovered, suggesting different immune strategies adopted by fish species. Among which, LECT2 was induced by up to 1000-fold upon infection, shedding new lights on the function of this gene. Our results constitute the first demonstration of a similar while different immune response in zebrafish and open new avenues for the investigation of evolutionary conserved and fish specific mechanisms of innate immunity.

Acute-Phase Reaction↗

PubMed2006

Distribution patterns of polychlorinated biphenyls in soils collected from Zhejiang province, east China.

Polychlorinated biphenyls (PCBs) were determined in surface soil samples from Zhejiang Province, east China. Concentrations of total PCBs ranged widely from 7.50 to 263 ng kg(-1) with a mean value of 45.4 ng kg(-1) (dry matter basis). In general, concentrations in soil samples from the southern part of the test area and especially from some sites near hills tended to be higher than those from other sites. The prevailing winds may have been the main factor influencing the spatial distribution of PCBs in soils. Other factors may have included the distribution of residential areas and land use variables. In this paper we also discuss the relationships between OCPs and PCBs in soils and relationships between these and land use variables as revealed by correlation analysis.

China↗

PubMed2006

3D computerized segmentation of lung volume with computed tomography.

Three-dimensional (3D)-based detection and diagnosis has an important role for significantly improving the detection and diagnosis of lung cancer upon computed tomography (CT). This report presents a 3D-based method for segmenting and visualizing lung volume by using CT images. An anisotropic filtering method was developed on CT slices to enhance the signal-to-noise ratio, and a wavelet transform-based interpolation method was used combined with volume rendering to construct the 3D volumetric data based on entire CT slices. Then an adaptive 3D region-growing algorithm was designed to segment lung volume, incorporated by automatic seed-locating methods through fuzzy logic algorithms and 3D morphological closing approaches. In addition, a 3D visualization tool was designed to view volumetric data, projections, or intersections of the lung volume at any view angle. This segmentation method was tested on single-detector CT images by percentage of volume overlap and percentage of volume difference. The experiment results show that the developed 3D-based segmentation method is effective and robust. This study lays the groundwork for 3D-based computerized detection and diagnosis of lung cancer with CT imaging. In addition, this approach can be integrated into a picture archiving and communication system serving as a visualization tool for radiologists' reading and interpretation.

Algorithms↗

PubMed2006

Better protection of pulmonary surfactant integrity with deep hypothermia and circulatory arrest.

BACKGROUND: The influence of deep hypothermia with either circulatory arrest (DHCA) or low-flow (DHLF) perfusion on pulmonary surfactant metabolism in neonates undergoing cardiac surgery remains unknown. This study was conducted to determine the influence of either strategy on surfactant metabolism and pulmonary function with neonatal piglet model. METHODS: Sixteen piglets underwent 90-minute deep hypothermia, either with circulatory arrest or low-flow perfusion (30 mL.kg(-1).min(-1)) at 18 degrees C. Disaturated phosphatidylcholine, total phospholipids, and total proteins from tracheal aspirates were measured serially until the end of cardiopulmonary bypass. Lung static compliance, airway resistance, and arterial blood oxygen partial pressure to inspired oxygen fraction were also measured. RESULTS: The DHLF caused more significant decrement of pulmonary static compliance than DHCA (3 +/- 0.4 mL.cmH2O(-1) vs 3.5 +/- 0.3 mL.cmH2O(-1) at 90 minutes of deep hypothermia). Arterial blood oxygen partial pressure to inspired oxygen fraction decreased more significantly after cardiopulmonary bypass in the DHLF group than the DHCA group (205 +/- 84 mm Hg vs 302 +/- 96 mm Hg). The DHLF caused more severe decrement of disaturated phosphatidylcholine total phospholipids (50% +/- 21% vs 67% +/- 23% of baseline at 90 minutes of deep hypothermia) and disaturated phosphatidylcholine total proteins (58% +/- 23% vs 73% +/- 23% of baseline at 90 minutes of deep hypothermia) than DHCA. More significant water retention developed in the lung in the DHLF group than in the DHCA group. The extent of surfactant depletion was statistically correlated with the extent of pulmonary functional deterioration in either group. CONCLUSIONS: The DHCA induces less injury on pulmonary surfactant metabolism and pulmonary function than DHLF.

Airway Resistance↗

PubMed2006

Role of oxidative stress in experimental sepsis and multisystem organ dysfunction.

Massive increase in radical species can lead to oxidative stress, promoting cell injury and death. This review focuses on experimental evidence of oxidative stress in critical illnesses, sepsis and multisystem organ dysfunction. Oxidative stress could negatively affect organ injury and thus overall survival of experimental models. Based on this experimental evidence, we could improve the rationale of supplementation of antioxidants alone or in combination with standard therapies aimed to reduce oxidative stress as novel adjunct treatment in critical care.

Animals↗

PubMed2006

Intravenous injection of methylprednisolone reduces the incidence of postextubation stridor in intensive care unit patients.

OBJECTIVE: To determine whether treatment with corticosteroids decreases the incidence of postextubation airway obstruction in an adult intensive care unit. DESIGN: Clinical experiment. SETTING: Adult medical and surgical intensive care unit of a teaching hospital. PATIENTS: One hundred twenty-eight patients who were intubated for >24 hrs with a cuff leak volume <24% of tidal volume and met weaning criteria. INTERVENTIONS: : Patients were randomized into a placebo group (control, n = 43) receiving four injections of normal saline every 6 hrs, a 4INJ group (n = 42) receiving four injections of methylprednisolone sodium succinate, or a 1INJ group (n = 42) receiving one injection of the corticosteroid followed by three injections of normal saline. Cuff volume was assessed 1 hr after each injection, and extubation was performed 1 hr after the last injection. Postextubation stridor was confirmed by examination using bronchoscopy or laryngoscopy. MEASUREMENTS AND MAIN RESULTS: The incidences of postextubation stridor were lower both in the 1INJ and the 4INJ groups than in the control group (11.6% and 7.1% vs. 30.2%, both p < .05), whereas there was no difference between the two treated groups (p = .46). The cuff leak volume increased after the second and fourth injection in the 4INJ group and after a second injection in the 1INJ group compared with the control group (both p < .05). CONCLUSIONS: A reduced cuff leak volume is a reliable indicator to identify patients at high risk to develop stridor. Treatment with a single or multiple injections of methylprednisolone can effectively reduce the occurrence of postextubation stridor.

Aged↗

PubMed2006

Pulmonary coagulopathy as a new target in therapeutic studies of acute lung injury or pneumonia--a review.

OBJECTIVES: To review the involvement of coagulation and fibrinolysis in the pathogenesis of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), pulmonary infection, and ventilator-induced lung injury (VILI). DATA SOURCE: Published articles on experimental and clinical studies of coagulation and fibrinolysis in ALI/ARDS, pneumonia, and mechanical ventilation. CONCLUSIONS: Alveolar fibrin deposition is an important feature of ALI/ARDS and pulmonary infection. The mechanisms that contribute to disturbed alveolar fibrin turnover are localized tissue factor-mediated thrombin generation and depression of bronchoalveolar urokinase plasminogen activator-mediated fibrinolysis, caused by the increase of plasminogen activator inhibitors. These effects on pulmonary coagulation and fibrinolysis are regulated by various proinflammatory cytokines and are similar to those found in the intravascular spaces during severe systemic inflammation. Some studies also suggest that pulmonary coagulopathy is a feature of VILI. Recent studies have demonstrated the beneficial effect of anticoagulant therapy in sepsis. Theoretical considerations suggest that this anticoagulant therapy will benefit patients with primary lung pathology including VILI, but clinical studies are needed to examine this hypothesis before such therapy is to be advocated as a standard of care in critically ill patients.

Blood Coagulation Disorders↗

PubMed2005

Human neutrophil peptides induce interleukin-8 production through the P2Y6 signaling pathway.

Antimicrobial human neutrophil peptides (HNPs) play a pivotal role in innate host defense against a broad spectrum of prokaryotic pathogens. In addition, HNPs modulate cellular immune responses by producing the chemokine interleukin-8 (IL-8) in myeloid and epithelial cells and by exerting chemotaxis to T cells, immature dendritic cells, and monocytes. However, the mechanisms by which HNPs modulate the immune responses in the eukaryotic cells remain unclear. We demonstrated that, as with adenosine triphosphate (ATP) and uridine diphosphate (UDP), HNP stimulation of human lung epithelial cells selectively induced IL-8 production in 10 pro- and anti-inflammatory cytokines examined. HNP-induced IL-8 release was inhibited by treatment with the nucleotide receptor antagonists suramin and reactive blue. Transfection of lung epithelial cells with antisense oligonucleotides targeting specific purinergic P2Y receptors revealed that the P2Y6 (ligand of UDP) signaling pathway plays a predominant role in mediating HNP-induced IL-8 production.

Base Sequence↗

PubMed2005

An intronic polyadenylation site in human and mouse CstF-77 genes suggests an evolutionarily conserved regulatory mechanism.

Human CstF-77 is one of the three subunits of cleavage stimulation factor (CstF) that is essential for mRNA polyadenylation. Its Drosophila homologue, suppressor of forked [su(f)], contains an intronic poly(A) site, which can lead to a short transcript without a stop codon. By both bioinformatic searches and validation with molecular biology experiments, we found that human and mouse CstF-77 genes also contain an intronic poly(A) site, which can be utilized to produce short CstF-77 transcripts lacking sequences encoding domains that are involved in many of the CstF-77 functions. The genomic sequence surrounding the poly(A) site is highly conserved among all vertebrates, but is not present in non-vertebrate species. Using public Serial Analysis of Gene Expression (SAGE) data, we found that the intronic poly(A) site is utilized in a wide range of tissues. This finding indicates that vertebrates may employ a similar alternative polyadenylation mechanism to modulate CstF-77, highlighting the importance of the regulation of CstF-77 in various species.

Alternative Splicing↗

PubMed2005

Biased alternative polyadenylation in human tissues.

BACKGROUND: Alternative polyadenylation is one of the mechanisms in human cells that give rise to a variety of transcripts from a single gene. More than half of the human genes have multiple polyadenylation sites (poly(A) sites), leading to variable mRNA and protein products. Previous studies of individual genes have indicated that alternative polyadenylation could occur in a tissue-specific manner. RESULTS: We set out to systematically investigate the occurrence and mechanism of alternative polyadenylation in different human tissues using bioinformatic approaches. Using expressed sequence tag (EST) data, we investigated 42 distinct tissue types. We found that several tissues tend to use poly(A) sites that are biased toward certain locations of a gene, such as sites located in introns or internal exons, and various sites in the exon located closest to the 3' end. We also identified several tissues, including eye, retina and placenta, that tend to use poly(A) sites not frequently used in other tissues. By exploring microarray expression data, we analyzed over 20 genes whose protein products are involved in the process or regulation of mRNA polyadenylation. Several brain tissues showed high concordance of gene expression of these genes with each other, but low concordance with other tissue types. By comparing genomic regions surrounding poly(A) sites preferentially used in brain tissues with those in other tissues, we identified several cis-regulatory elements that were significantly associated with brain-specific poly(A) sites. CONCLUSION: Our results indicate that there are systematic differences in poly(A) site usage among human tissues, and both trans-acting factors and cis-regulatory elements may be involved in regulating alternative polyadenylation in different tissues.

Brain↗

PubMed2005

The role of oxidative stress in adult critical care.

Oxidative stress defines an imbalance in production of oxidizing chemical species and their effective removal by protective antioxidants and scavenger enzymes. Evidence of massive oxidative stress is well established in adult critical illnesses characterized by tissue ischemia-reperfusion injury and by an intense systemic inflammatory response such as during sepsis and acute respiratory distress syndrome. Oxidative stress could exacerbate organ injury and thus overall clinical outcome. We searched MEDLINE databases (January 1966 to June 2005). For interventional studies, we accepted only randomized trials. Several small clinical trials have been performed in order to reduce oxidative stress by supplementation of antioxidants alone or in combination with standard therapies. These studies have reported controversial results. Newer large multicenter trials with antioxidant supplementation should be performed, considering administration at an early stage of illness and a wider population of critically ill patients.

Adult↗