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61.
Currently, a wide variety of both polyclonal and monoclonal antibodies are being routinely utilized to prevent and treat solid organ rejection. More commonly, these agents are also administered in order to delay introduction of calcineurin inhibitors, especially in patients with already compromised renal function. While these antibody therapies dramatically reduced the incidence of acute rejection episodes and improved both short and long-term graft survival, they are also associated with an increased incidence of opportunistic infections and neoplastic complications. Therefore, effective patient management must necessarily balance these risks against the potential benefits of the therapy.Key words: monoclonal, polyclonal, induction, transplants, kidney, lung, liver, heart, rejection, complications 相似文献
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Induction of autophagy by an oleanolic acid derivative,SZC017, promotes ROS‐dependent apoptosis through Akt and JAK2/STAT3 signaling pathway in human lung cancer cells
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Tavoulari S Rizwan AN Forrest LR Rudnick G 《The Journal of biological chemistry》2011,286(4):2834-2842
In ion-coupled transport proteins, occupation of selective ion-binding sites is required to trigger conformational changes that lead to substrate translocation. Neurotransmitter transporters, targets of abused and therapeutic drugs, require Na(+) and Cl(-) for function. We recently proposed a chloride-binding site in these proteins not present in Cl(-)-independent prokaryotic homologues. Here we describe conversion of the Cl(-)-independent prokaryotic tryptophan transporter TnaT to a fully functional Cl(-)-dependent form by a single point mutation, D268S. Mutations in TnaT-D268S, in wild type TnaT and in serotonin transporter provide direct evidence for the involvement of each of the proposed residues in Cl(-) coordination. In both SERT and TnaT-D268S, Cl(-) and Na(+) mutually increased each other's potency, consistent with electrostatic interaction through adjacent binding sites. These studies establish the site where Cl(-) binds to trigger conformational change during neurotransmitter transport. 相似文献
66.
Apoptosis, or programmed cell death, plays a pivotal role in the elimination of unwanted, damaged, or infected cells in multicellular organisms and also in diverse biological processes, including development, cell differentiation, and proliferation. Apoptosis is a highly regulated form of cell death, and dysregulation of apoptosis results in pathological conditions including cancer, autoimmune and neurodegenerative diseases. The Bcl-2 family proteins are key regulators of apoptosis, which include both anti- and pro-apoptotic proteins, and a slight change in the dynamic balance of these proteins may result either in inhibition or promotion of cell death. Execution of apoptosis by various stimuli is initiated by activating either intrinsic or extrinsic pathways which lead to a series of downstream cascade of events, releasing of various apoptotic mediators from mitochondria and activation of caspases, important for the cell fate. In view of recent research advances about underlying mechanism of apoptosis, this review highlights the basics concept of apoptosis and its regulation by Bcl-2 family of protein. Furthermore, this review discusses the interplay of various apoptotic mediators and caspases to decide the fate of the cell. We expect that this review will add to the pool of basic information necessary to understand the mechanism of apoptosis which may implicate in designing better strategy to develop biomedical therapy to control apoptosis. 相似文献
67.
Sultana Juhara Mannan Mohammad Abul Kalam Azad Md. Ashik Ullah Abdullah Al Maruf Md. Israt Rayhan Mohammad Shamsul Ahsan Abul Hasnat 《Biological trace element research》2011,140(3):272-283
Drug abuser patients (n = 104), age ranging from 19 to 42 years, were randomly recruited to investigate the serum levels of trace elements (Cu, Zn,
Fe, and Mg), malondialdehyde (MDA), and immunoglobulin (IgG, IgA, and IgM) before and after clinical intervention. Control
group also included 104 healthy individuals. Blood samples were analyzed for determining trace elements, MDA, and immunoglobulin
using atomic absorption spectroscopy, Ultraviolet-Visible (UV-VIS) spectroscopy, and turbidimetry method, respectively. For
serum level of Zn and Fe, the differences between the groups (before intervention, after intervention, and control) were not
significant (p > 0.05). However, significant differences were found in serum copper levels between control group, drug abuser patients,
and before and after intervention (p < 0.05). The concentration of Mg was found to be significantly higher (p = 0.007) in drug abuser patients than the controls, and after intervention, the level was restored to control value. A displacement
of elemental homeostasis was observed in drug abuser patients compared to control, and it was improved after intervention.
An increase in serum concentration of MDA was found in drug abuser patients compared to control subjects (p > 0.05) but was not statistically significant. After intervention, the concentration was restored to control value (p > 0.05). The serum concentrations of IgA and IgM were found to be significantly higher (p < 0.05) in drug abuser patients before intervention than the controls, and the level tended to be restored to control level
after clinical intervention. Serum IgG level was found to be lower in drug abuser patients compared to controls and further
declined significantly (p < 0.05) after intervention. These findings may suggest a possible imbalance in the levels of micronutrients, antioxidants,
and immunoglobulin in drug abuser patients, which tend to be restored to control values after detoxification. 相似文献
68.
Abdul Wadood Muhammad Riaz Amir ul Mulk Momin Khan Sobia Ahsan Haleem Sulaiman Shams Sahib Gul Ayaz Ahmed Muhammad Qasim Farman Ali Zaheer Ul-Haq 《Bioinformation》2014,10(5):299-307
Urease is an important enzyme both in agriculture and medicine research. Strategies based on urease inhibition is critically
considered as the first line treatment of infections caused by urease producing bacteria. Since, urease possess agro-chemical and
medicinal importance, thus, it is necessary to search for the novel compounds capable of inhibiting this enzyme. Several
computational methods were employed to design novel and potent urease inhibitors in this work. First docking simulations of
known compounds consists of a set of arylidine barbiturates (termed as reference) were performed on the Bacillus pasteurii (BP)
urease. Subsequently, two fold strategies were used to design new compounds against urease. Stage 1 comprised of the energy
minimization of enzyme-ligand complexes of reference compounds and the accurate prediction of the molecular mechanics
generalized born (MMGB) interaction energies. In the second stage, new urease inhibitors were then designed by the substitution
of different groups consecutively in the aryl ring of the thiobarbiturates and N, N-diethyl thiobarbiturates of the reference ligands..
The enzyme-ligand complexes with lowest interaction energies or energies close to the calculated interaction energies of the
reference molecules, were selected for the consequent chemical manipulation. This was followed by the substitution of different
groups on the 2 and 5 positions of the aryl ring. As a result, several new and potent diethyl thiobarbiturates were predicted as
urease inhibitors. This approach reflects a logical progression for early stage drug discovery that can be exploited to successfully
identify potential drug candidates. 相似文献
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While genetic screens have identified mutants of the model legume Lotus japonicus that can nodulate in the absence of rhizobia, the lack of a proteome map is a major hindrance to understanding the functional protein networks associated with this nodulation process. In this issue of Proteomics, Dam et al. (Proteomics 2014, 14, 230–240) developed 2D gel‐based reference maps of nodules and roots of Lotus and a spontaneous nodule formation mutant (snf1). Comparative proteomic analysis of roots and two developmental stages of nodules provide useful insights into tissue‐specific mechanisms underlying nodule organogenesis. Additionally, a comparison of interspecies nodule proteomes displays that overlapping and individual mechanisms are associated with legume nodulation. 相似文献