Biomedical subjects

Zhi-Wei Li

Publications and source records attributed to Zhi-Wei Li.

15 recordsLinked to original sources

PubMed2006

Tumor microenvironment and drug resistance in hematologic malignancies.

Increasing evidence supports the role of the tumor microenvironment in conferring drug resistance as a major cause of relapse and incurability of cancers. The tumor microenvironment consists of normal stromal cells, extracellular matrix, and soluble factors such as cytokines and growth factors. Tumor-tumor cell interaction, tumor-stromal cell interaction, as well as tumor-ECM interaction, all contribute to direct cell contact mediated drug resistance. In addition, soluble factors produced in the tumor microenvironment provide further signals for tumor cell growth and survival. Environment mediated-drug resistance (EM-DR) could be considered as the totality of cell adhesion mediated drug resistance (CAM-DR) and soluble factor mediated drug resistance (SM-DR) produced by the tumor-host interaction. This review focuses on the EM-DR model system and signaling pathways involved in cell survival of hematological malignancies.

Cell Survival↗

PubMed2006

[Study on intelligent system of hyper-spectral data gathering based on wireless data communication technology in farm machinery].

In order to meet the needs of highly dense and overall farmland information gathering, wireless data communicating, and real-time processing in the precision agriculture, this system integrated GPS, GIS and RS based on the technology of computer and wireless data transmission. On the one hand, the system makes DGPS and Hyper-spectrograph integrated through the AT891v52 MCU, providing the accurate space position and realizing the integration of spectrum data acquisition and orientation. On the other hand, the system realizes the communication between the data gathering control system and the microcomputer by using the nRF905 system. Meanwhile the system has realized the visualized analysis and management of the spectrum data by integrating Visual Basic and Map-Objects into GIS, displaying real-time trace of moving point and some related attributes of the moving point in map layers, and calculating crop derivative spectra and crop vegetation index NDVI etc. Thus, sufficient information was provided for expert system and decision support system of precision agriculture.

English Abstract↗

PubMed2005

IKK-beta links inflammation to obesity-induced insulin resistance.

Inflammation may underlie the metabolic disorders of insulin resistance and type 2 diabetes. IkappaB kinase beta (IKK-beta, encoded by Ikbkb) is a central coordinator of inflammatory responses through activation of NF-kappaB. To understand the role of IKK-beta in insulin resistance, we used mice lacking this enzyme in hepatocytes (Ikbkb(Deltahep)) or myeloid cells (Ikbkb(Deltamye)). Ikbkb(Deltahep) mice retain liver insulin responsiveness, but develop insulin resistance in muscle and fat in response to high fat diet, obesity or aging. In contrast, Ikbkb(Deltamye) mice retain global insulin sensitivity and are protected from insulin resistance. Thus, IKK-beta acts locally in liver and systemically in myeloid cells, where NF-kappaB activation induces inflammatory mediators that cause insulin resistance. These findings demonstrate the importance of liver cell IKK-beta in hepatic insulin resistance and the central role of myeloid cells in development of systemic insulin resistance. We suggest that inhibition of IKK-beta, especially in myeloid cells, may be used to treat insulin resistance.

Animals↗

PubMed2005

Activation of IKK by thymosin alpha1 requires the TRAF6 signalling pathway.

Thymosin alpha1 (T(alpha)1) is noted for its immunomodulatory activities and therapeutic potential in treatment of infectious diseases and cancer. However, the molecular mechanism of its effectiveness is not completely understood. Here, we report that T(alpha)1 induces interleukin (IL)-6 expression through the I(kappa)B kinase (IKK) and nuclear factor-(kappa)B (NF-(kappa)B) pathway. Using IKK(beta)-deficient bone-marrow-derived macrophages and mouse embryo fibroblasts (MEFs), we show that IKK(beta) is essential for IKK and NF-(kappa)B activation as well as efficient IL-6 induction. Further analysis using tumour necrosis factor receptor-associated factor 6 (TRAF6)-deficient MEFs shows that TRAF6 is crucial for activation of IKK and induction of IL-6 by Talpha1. Intriguingly, T(alpha)1 triggers protein kinase C (PKC)iota/zeta activation, which is TRAF6 dependent and involves IKK. In addition, T(alpha)1 induces the formation of a signalsome composed of TRAF6, p62 and PKC(iota)/zeta as well as IKK. Thus, our study identifies T(alpha)1 as a unique activator of the TRAF6 signal pathway and provides a cohesive interpretation of the molecular basis of the therapeutic utility of T(alpha)1.

Animals↗

PubMed2005

Early enteral and parenteral nutritional support in patients with cirrhotic portal hypertension after pericardial devascularization.

BACKGROUND: The abnormal metabolism caused by cirrhosis always results in a complex problem about nutritional support, which will be more intricate while patients with portal hypertension are treated with pericardial devascularization. Comparing the effects of early enteral and parenteral nutritional support in patients with cirrhotic portal hypertension after pericardial devascularization, we try to realize the advantages and disadvantages of the two nutritional therapies and to guide our clinical practice. METHODS: After pericardial devascularization, 40 patients with cirrhotic portal hypertension were divided randomly into 2 groups: enteral and parenteral nutritional support, respectively. The general nutritional condition, capability of producing protein, liver function, blood velocity of the portal vein, gut function, bowel bacterial translocation, mortality, complication rate, stay in ICU, duration of hospitalization and costs of treatment were determined in all the patients and compared between the 2 groups. RESULTS: Both enteral and parenteral nutritional supports could improve the general nutrition condition of the patients; but patients receiving enteral nutritional support had fewer complications. Enteral nutrition was more effective than parenteral nutrition in increasing the blood velocity of the portal vein, stimulating gut motion, preventing bowel bacterial translocation, shortening the stay in ICU and the duration of hospitalization, and saving costs of treatment. CONCLUSION: After pericardial devascularization, patients with cirrhotic portal hypertension should be treated with enteral nutritional support as early as possible.

Adult↗

PubMed2004

IKKbeta links inflammation and tumorigenesis in a mouse model of colitis-associated cancer.

A link between inflammation and cancer has long been suspected, but its molecular nature remained ill defined. A key player in inflammation is transcription factor NF-kappaB whose activity is triggered in response to infectious agents and proinflammatory cytokines via the IkappaB kinase (IKK) complex. Using a colitis-associated cancer model, we show that although deletion of IKKbeta in intestinal epithelial cells does not decrease inflammation, it leads to a dramatic decrease in tumor incidence without affecting tumor size. This is linked to increased epithelial apoptosis during tumor promotion. Deleting IKKbeta in myeloid cells, however, results in a significant decrease in tumor size. This deletion diminishes expression of proinflammatory cytokines that may serve as tumor growth factors, without affecting apoptosis. Thus, specific inactivation of the IKK/NF-kappaB pathway in two different cell types can attenuate formation of inflammation-associated tumors. In addition to suppressing apoptosis in advanced tumors, IKKbeta may link inflammation to cancer.

Animals↗

PubMed2004

IkappaB-kinasebeta-dependent NF-kappaB activation provides radioprotection to the intestinal epithelium.

Acute injury to the intestinal mucosa is a major dose-limiting complication of abdominal radiation therapy. We studied the role of the transcription factor NF-kappaB in protection against radiation-induced apoptosis in the intestinal epithelium in vivo. We use mice in which NF-kappaB signaling through IkappaB-kinase (IKK)-beta is selectively ablated in intestinal epithelial cells to show that failure to activate epithelial cell NF-kappaB in vivo results in a significant increase in radiation-induced epithelial cell apoptosis. Furthermore, bacterial lipopolysaccharide, which is normally a radioprotective agent, is radiosensitizing in IKKbeta-deficient intestinal epithelial cells. Increased apoptosis in IKKbeta-deficient intestinal epithelial cells was accompanied by increased expression and activation of the tumor suppressor p53 and decreased expression of antiapoptotic Bcl-2 family proteins. These results demonstrate the physiological importance of the NF-kappaB system in protection against radiation-induced death in the intestinal epithelium in vivo and identify IKKbeta as a key molecular target for radioprotection in the intestine. Selective preactivation of NF-kappaB through IKKbeta in intestinal epithelial cells could provide a therapeutic modality that allows higher doses of radiation to be tolerated during cancer radiotherapy.

Animals↗

PubMed2004

Genetic dissection of antigen receptor induced-NF-kappaB activation.

NF-kappaB is a master transcription factor in the immune system. It regulates various aspects of immune cell development, homeostasis, survival and function. It is in these contexts that the signaling pathways leading to NF-kappaB activation are best understood. This review addresses the cell signaling from antigen receptors as well as Toll-like receptors to NF-kappaB in both innate and adaptive immunity as revealed by the analysis of mice lacking specific signaling intermediates.

Animals↗

PubMed2004

Low SO2 emission from CFB co-firing MSW and bituminous.

Influence of co-firing rate on SO2 emission from co-firing municipal solid waste (MSW) and bituminous containing high amount of sulfur (1.79%) was studied in a 0.15 MWt circulating fluidized bed (CFB). The temperature selected is 1123 K, typical for MSW incineration using CFB. The particle concentration in the dilution zone of the furnace, the alkali metal concentration and sulfate concentration in the recirculating ash and fly ash, and flue gas composition were determined. The results showed that the addition of MSW leads to a significant decrease in SO2 emission. Concentration of SO2 in flue gas decreased to 0 with the co-firing rate greater than 51%. This reduction in SO2 emission is attributed both to the high particle concentration in the dilution zone of the furnace, the high content of alkali metals in the bed material, and to the comparatively high concentration of HCI in flue gas during co-firing of MSW and bituminous.

Air Pollutants↗

PubMed2003

IKK beta is required for peripheral B cell survival and proliferation.

NF-kappaB activity in mammalian cells is regulated through the IkappaB kinase (IKK) complex, consisting of two catalytic subunits (IKKalpha and IKKbeta) and a regulatory subunit (IKKgamma). Targeted deletion of Ikkbeta results in early embryonic lethality, thus complicating the examination of IKKbeta function in adult tissues. Here we describe the role of IKKbeta in B lymphocytes made possible by generation of a mouse strain that expresses a conditional Ikkbeta allele. We find that the loss of IKKbeta results in a dramatic reduction in all peripheral B cell subsets due to associated defects in cell survival. IKKbeta-deficient B cells are also impaired in mitogenic responses to LPS, anti-CD40, and anti-IgM, indicating a general defect in the ability to activate the canonical NF-kappaB signaling pathway. These findings are consistent with a failure to mount effective Ab responses to T cell-dependent and independent Ags. Thus, IKKbeta provides a requisite role in B cell activation and maintenance and thus is a key determinant of humoral immunity.

Animals↗

PubMed2003

The two faces of IKK and NF-kappaB inhibition: prevention of systemic inflammation but increased local injury following intestinal ischemia-reperfusion.

We studied the role of NF-kappaB in acute inflammation caused by gut ischemia-reperfusion through selective ablation of IkappaB kinase (IKK)-beta, the catalytic subunit of IKK that is essential for NF-kappaB activation. Ablation of IKK-beta in enterocytes prevented the systemic inflammatory response, which culminates in multiple organ dysfunction syndrome (MODS) that is normally triggered by gut ischemia-reperfusion. IKK-beta removal from enterocytes, however, also resulted in severe apoptotic damage to the reperfused intestinal mucosa. These results show the dual function of the NF-kappaB system, which is responsible for both tissue protection and systemic inflammation, and underscore the caution that should be exerted in using NF-kappaB and IKK inhibitors.

Animals↗

PubMed2003

IKKbeta is required for prevention of apoptosis mediated by cell-bound but not by circulating TNFalpha.

IkappaB kinase beta (IKKbeta) is required for NF-kappaB activation and suppression of TNFalpha-mediated liver apoptosis. To investigate how IKKbeta suppresses apoptosis, we generated hepatocyte-specific Ikkbeta knockout mice, Ikkbeta(Deltahep), which exhibit little residual NF- kappaB activity but are healthy with normal liver function. Unexpectedly, Ikkbeta(Deltahep) mice are slightly more sensitive than controls to LPS-induced liver apoptosis but are highly susceptible to liver destruction following concanavalin A (ConA)-induced T cell activation. Unlike LPS, a potent inducer of circulating TNFalpha, ConA exerts cytotoxic effects through cell-bound TNFalpha, which activates type 1 and 2 TNF receptors (TNFR). While TNFR2 does not contribute to NF-kappaB activation, it is important for ConA-induced JNK activation, which is augmented by the absence of IKKbeta. Using JNK-deficient mice we show that JNK is required for ConA-induced liver damage. Thus, the antiapoptotic function of IKKbeta, which is most critical in situations that involve cell-bound TNFalpha, is mediated partially through attenuation of JNK activity.

Animals↗

PubMed2002

Macrophage apoptosis by anthrax lethal factor through p38 MAP kinase inhibition.

The bacterium Bacillus anthracis causes the death of macrophages, which may allow it to avoid detection by the innate immune system. We found that B. anthracis lethal factor (LF) selectively induces apoptosis of activated macrophages by cleaving the amino-terminal extension of mitogen-activated protein kinase (MAPK) kinases (MKKs) that activate p38 MAPKs. Because macrophages that are deficient in transcription factor nuclear factor kappaB (NF-kappaB) are also sensitive to activation-induced death and p38 is required for expression of certain NF-kappaB target genes, p38 is probably essential for synergistic induction of those NF-kappaB target genes that prevent apoptosis of activated macrophages. This dismantling of the p38 MAPK module represents a strategy used by B. anthracis to paralyze host innate immunity.

Animals↗

PubMed2002

The lymphotoxin-beta receptor induces different patterns of gene expression via two NF-kappaB pathways.

The lymphotoxin-beta receptor (LTbetaR) plays critical roles in inflammation and lymphoid organogenesis through activation of NF-kappaB. In addition to activation of the classical NF-kappaB, ligation of this receptor induces the processing of the cytosolic NF-kappaB2/p100 precursor to yield the mature p52 subunit, followed by translocation of p52 to the nucleus. This activation of NF-kappaB2 requires NIK and IKKalpha, while NEMO/IKKgamma is dispensable for p100 processing. IKKbeta-dependent activation of canonical NF-kappaB is required for the expression but not processing of p100 and for the expression of proinflammatory molecules including VCAM-1, MIP-1beta, and MIP-2 in response to LTbetaR ligation. In contrast, IKKalpha controls the induction by LTbetaR ligation of chemokines and cytokines involved in lymphoid organogenesis, including SLC, BLC, ELC, SDF1, and BAFF.

Active Transport, Cell Nucleus↗

PubMed2002

NF-kappaB in cancer: from innocent bystander to major culprit.

Nuclear factor of kappaB (NF-kappaB) is a sequence-specific transcription factor that is known to be involved in the inflammatory and innate immune responses. Although the importance of NF-KB in immunity is undisputed, recent evidence indicates that NF-kappaB and the signalling pathways that are involved in its activation are also important for tumour development. NF-kappaB should therefore receive as much attention from cancer researchers as it has already from immunologists.

Animals↗