The anti-inflammatory effects of the new ster-oidal antedrug, 21-acetyloxy-9α-fluoro-11β-hy-droxyl-3, 20-dioxo-1, 4-pregnadieno-[16α, 17α-d] isoxazoline (FP-ISO-21AC), on nitric oxide (NO) and interleukin 8 (IL-8)...The anti-inflammatory effects of the new ster-oidal antedrug, 21-acetyloxy-9α-fluoro-11β-hy-droxyl-3, 20-dioxo-1, 4-pregnadieno-[16α, 17α-d] isoxazoline (FP-ISO-21AC), on nitric oxide (NO) and interleukin 8 (IL-8) production, were inves-tigated together with its parent steroid predni-solone (PRED). PRED is one of the anti-in-flammatory steroids but has systemic side ef-fects which limit the use of it. PRED was modi-fied with ‘antedrug concept’ to create safer drugs that attack problems such as inflamma-tion, then quickly become inactive before they can cause systemic side effect. We had a test about the effect of the modified anti-inflamma-tory steroidal antedrug on anti-inflammatory activity. The present study evaluated their ability to inhibit cytokine-induced NO and IL-8 produc-tion in human alveolar epithelial cells. We also investigated their ability to enhance the expres-sion of inhibitory cytokine receptor, interleukin 22 receptor (IL-22R) in human alveolar epithelial cells. Our results showed that FP-ISO-21AC sh- owed higher ability to inhibit the cytokine - in-duced production of NO than PRED. Exogenous IL-22 was added to the media of both human alveolar epithelial cells (A549) and human lung fibroblast (HLF-1). In the presence of the ex-ogenous inhibitory cytokine IL-22, further re-duction of NO production was observed in A549 cells, which express IL-22R, but not in HLF1, which does not express IL-22R. These data suggested that the steroidal antedrugs en-hanced the expression of IL-22R. FP-ISO- 21AC showed higher potency than PRED to restore the expression of IL-22R. FP-ISO-21AC further reduced NO production to 27% and PRED further reduced NO production to 39%. In con-clusion, a synthesized steroidal antedrug FP- ISO-21AC showed higher anti-inflammatory ef-fects than PRED by inhibiting the expression of pro-inflammatory mediator NO and stimulating the expression of IL-22R.展开更多
Inhibition of mammalian target of rapamycin (m- TOR) is a potential method for cancer treatment. Effects of rapamycin (RAP) on the reversion of malignant breast epithelial cells were investigated on three-dimensional ...Inhibition of mammalian target of rapamycin (m- TOR) is a potential method for cancer treatment. Effects of rapamycin (RAP) on the reversion of malignant breast epithelial cells were investigated on three-dimensional (3D) basement membrane extract (BME) cultures. Through continuous exposure to 20 nM of RAP, cell colony size was significantly reduced in 3D BME cultures of malignant breast epithelial cells, while normal cell colony size appeared unaffected. In unfixed 3D BME cultures of normal and RAP-treated malignant breast epithelial cells, the presence of luminal cell death was confirmed by ethidium bromide and propidium iodide labeling. Increased structural organization was observed by im- munofluorescence staining of F-actin and β-catenin in RAP-treated malignant breast epithelial cells. In monolayer cultures of normal and malignant breast epithelial cells, continuous exposure to 20 nM of RAP increased caspase 3/7 activity and decreased proliferation. Reverse transcriptase polymerase ch- ain reaction (RT-PCR) array analysis indicated a fold increase in the expression of a number of proteins related to polarity, cell-cell adhesion, and cell-matrix adhesion in the presence of RAP. Our data showed that phenotypic reversion of malignancy can be ach- ieved through RAP exposure on 3D BME cultures. This 3D BME culture system will provide correct microenvironments for observing the effects of other mTOR inhibitors on phenotypic reversion of malignant breast epithelial cells.展开更多
Alzheimer’s disease (AD) is considered a slow neuronal dysfunction process through hypoxia, ischemia and leads to apoptosis mediated senile plaques and neurofibrillary tangles (NFTs). Due to non-invasive approach of ...Alzheimer’s disease (AD) is considered a slow neuronal dysfunction process through hypoxia, ischemia and leads to apoptosis mediated senile plaques and neurofibrillary tangles (NFTs). Due to non-invasive approach of plaque characterization, computational techniques based on Brownian dynamics simulation are unique to speculate the electrostatic and kinetic properties of Acetylcho-linesterase (AChE). Typically the MRI spectros-copy high choline peak and enzyme specific to Alzheimer’s Disease (specificity constant (kcat/Km) of AChE) appeared associated with apoptosis and hypoxia. A simple display between synergy of cytokines, apoptosis, elevated AChE and choline is postulated as initial events. The events may be distributed heterogeneously within the senile plaques and neurofibrillary tangles (NFTs) of Alzheimer’s Disease (AD). The role of decreased brain AChE and synergy was associated with specific Magnetic Resonance Spectroscopic (MRS) pattern profiles in AD. These findings suggest that that the altered AChE and early apoptosis events in AD may be associated with specific MR spectral peak patterns. This study opens the possibility of reduced AChE levels causing high choline and reduced N-acetyl ace-tate (NAA) neurotransmitter by MRS after initial apoptosis and/or inflammation to make amyloid plaques in the cerebral tissue of Alzheimer’s disease (AD) patients. These results can be useful in clinical trials on AD lesions.展开更多
Background: In the last decade, sodium mag-netic resonance imaging was investigated for its potential as a functional cardiac imaging tool for ischemia. Later interest was developed in contrast enhancement for intrace...Background: In the last decade, sodium mag-netic resonance imaging was investigated for its potential as a functional cardiac imaging tool for ischemia. Later interest was developed in contrast enhancement for intracellular sodium. Little success was reported to suppress extracellular sodium resulting in the intracellular sodium MRI image acquisition using quantum filters or sodium transition states as contrast properties. Now its clinical application is ex-panding as a new challenge in brain and other cancer tumors. Contrast enhancement: We highlight the physical principles of sodium MRI in three different pulse sequences using filters (single quantum, multiple quantum, and triple quantum) meant for sodium contrast enhancement. The optimization of scan parameters, i.e. times of echo delay (TE), inversion recovery (TI) periods, and utility of Dysprosium (DyPPP) shift contrast agents, enhances contrast in sodium MRI images. Inversion recovery pulse sequence without any shift reagent measures the intracellular sodium concentration to evaluate ischemia, apoptosis and membrane integrity. Membrane integrity loss, apoptosis and malignancy are results of growth factor loss and poor epithelial capability related with MRI visible intracellular sodium concentration. Applications and limitations: The sodium MR imaging technical advances reduced scan time to distinguish intracellular and extracellular sodium signals in malignant tumors by use of quantum filter techniques to generate 3D sodium images without shift regents. We observed the association of malignancy with increased TSC, and reduced apoptosis and epithelial growth factor in breast cancer cells. The validity is still in question. Conclusion: Different modified sodium MRI pulse sequences are research tools of sodium contrast enhancement in brain, cardiac and tumor imaging. The optimized MRI scan pa-rameters in quantum filter techniques generate contrast in intracellular sodium MR images without using invasive contrast shift agents. Still, validity and clinical utility are in展开更多
The temperature and magnetic moment depend-ence for assessing localized heating utilizing a new class of Manganese-Zinc-Gadolinium mag-netic nanoparticles was studied. These particles showed heating effect when subjec...The temperature and magnetic moment depend-ence for assessing localized heating utilizing a new class of Manganese-Zinc-Gadolinium mag-netic nanoparticles was studied. These particles showed heating effect when subjected to alter-nating filed. Alternatively, a new approach was used to get disperse heating without spot heating by using the synthesis of particles at controlled Curie temperature of less than 44oC. The study reports a simple synthesis of Mn0.5Zn0.5GdxFe(2-x)O4 nanoparticles using chemical co- precipita-tion technique. The particles exhibited Curie temperature of 42篊 and high magnitude of mag-netic moments. The particles showed sigmoid behavior of dependence between temperature and magnetic moments. The Nuclear Magnetic Resonance spectroscopy showed T1 depend-ence on temperature in the range of 10-45篊. The particles may have high promise for self con-trolled magnetic hyperthermia application and its monitoring.展开更多
文摘The anti-inflammatory effects of the new ster-oidal antedrug, 21-acetyloxy-9α-fluoro-11β-hy-droxyl-3, 20-dioxo-1, 4-pregnadieno-[16α, 17α-d] isoxazoline (FP-ISO-21AC), on nitric oxide (NO) and interleukin 8 (IL-8) production, were inves-tigated together with its parent steroid predni-solone (PRED). PRED is one of the anti-in-flammatory steroids but has systemic side ef-fects which limit the use of it. PRED was modi-fied with ‘antedrug concept’ to create safer drugs that attack problems such as inflamma-tion, then quickly become inactive before they can cause systemic side effect. We had a test about the effect of the modified anti-inflamma-tory steroidal antedrug on anti-inflammatory activity. The present study evaluated their ability to inhibit cytokine-induced NO and IL-8 produc-tion in human alveolar epithelial cells. We also investigated their ability to enhance the expres-sion of inhibitory cytokine receptor, interleukin 22 receptor (IL-22R) in human alveolar epithelial cells. Our results showed that FP-ISO-21AC sh- owed higher ability to inhibit the cytokine - in-duced production of NO than PRED. Exogenous IL-22 was added to the media of both human alveolar epithelial cells (A549) and human lung fibroblast (HLF-1). In the presence of the ex-ogenous inhibitory cytokine IL-22, further re-duction of NO production was observed in A549 cells, which express IL-22R, but not in HLF1, which does not express IL-22R. These data suggested that the steroidal antedrugs en-hanced the expression of IL-22R. FP-ISO- 21AC showed higher potency than PRED to restore the expression of IL-22R. FP-ISO-21AC further reduced NO production to 27% and PRED further reduced NO production to 39%. In con-clusion, a synthesized steroidal antedrug FP- ISO-21AC showed higher anti-inflammatory ef-fects than PRED by inhibiting the expression of pro-inflammatory mediator NO and stimulating the expression of IL-22R.
文摘Inhibition of mammalian target of rapamycin (m- TOR) is a potential method for cancer treatment. Effects of rapamycin (RAP) on the reversion of malignant breast epithelial cells were investigated on three-dimensional (3D) basement membrane extract (BME) cultures. Through continuous exposure to 20 nM of RAP, cell colony size was significantly reduced in 3D BME cultures of malignant breast epithelial cells, while normal cell colony size appeared unaffected. In unfixed 3D BME cultures of normal and RAP-treated malignant breast epithelial cells, the presence of luminal cell death was confirmed by ethidium bromide and propidium iodide labeling. Increased structural organization was observed by im- munofluorescence staining of F-actin and β-catenin in RAP-treated malignant breast epithelial cells. In monolayer cultures of normal and malignant breast epithelial cells, continuous exposure to 20 nM of RAP increased caspase 3/7 activity and decreased proliferation. Reverse transcriptase polymerase ch- ain reaction (RT-PCR) array analysis indicated a fold increase in the expression of a number of proteins related to polarity, cell-cell adhesion, and cell-matrix adhesion in the presence of RAP. Our data showed that phenotypic reversion of malignancy can be ach- ieved through RAP exposure on 3D BME cultures. This 3D BME culture system will provide correct microenvironments for observing the effects of other mTOR inhibitors on phenotypic reversion of malignant breast epithelial cells.
文摘Alzheimer’s disease (AD) is considered a slow neuronal dysfunction process through hypoxia, ischemia and leads to apoptosis mediated senile plaques and neurofibrillary tangles (NFTs). Due to non-invasive approach of plaque characterization, computational techniques based on Brownian dynamics simulation are unique to speculate the electrostatic and kinetic properties of Acetylcho-linesterase (AChE). Typically the MRI spectros-copy high choline peak and enzyme specific to Alzheimer’s Disease (specificity constant (kcat/Km) of AChE) appeared associated with apoptosis and hypoxia. A simple display between synergy of cytokines, apoptosis, elevated AChE and choline is postulated as initial events. The events may be distributed heterogeneously within the senile plaques and neurofibrillary tangles (NFTs) of Alzheimer’s Disease (AD). The role of decreased brain AChE and synergy was associated with specific Magnetic Resonance Spectroscopic (MRS) pattern profiles in AD. These findings suggest that that the altered AChE and early apoptosis events in AD may be associated with specific MR spectral peak patterns. This study opens the possibility of reduced AChE levels causing high choline and reduced N-acetyl ace-tate (NAA) neurotransmitter by MRS after initial apoptosis and/or inflammation to make amyloid plaques in the cerebral tissue of Alzheimer’s disease (AD) patients. These results can be useful in clinical trials on AD lesions.
文摘Background: In the last decade, sodium mag-netic resonance imaging was investigated for its potential as a functional cardiac imaging tool for ischemia. Later interest was developed in contrast enhancement for intracellular sodium. Little success was reported to suppress extracellular sodium resulting in the intracellular sodium MRI image acquisition using quantum filters or sodium transition states as contrast properties. Now its clinical application is ex-panding as a new challenge in brain and other cancer tumors. Contrast enhancement: We highlight the physical principles of sodium MRI in three different pulse sequences using filters (single quantum, multiple quantum, and triple quantum) meant for sodium contrast enhancement. The optimization of scan parameters, i.e. times of echo delay (TE), inversion recovery (TI) periods, and utility of Dysprosium (DyPPP) shift contrast agents, enhances contrast in sodium MRI images. Inversion recovery pulse sequence without any shift reagent measures the intracellular sodium concentration to evaluate ischemia, apoptosis and membrane integrity. Membrane integrity loss, apoptosis and malignancy are results of growth factor loss and poor epithelial capability related with MRI visible intracellular sodium concentration. Applications and limitations: The sodium MR imaging technical advances reduced scan time to distinguish intracellular and extracellular sodium signals in malignant tumors by use of quantum filter techniques to generate 3D sodium images without shift regents. We observed the association of malignancy with increased TSC, and reduced apoptosis and epithelial growth factor in breast cancer cells. The validity is still in question. Conclusion: Different modified sodium MRI pulse sequences are research tools of sodium contrast enhancement in brain, cardiac and tumor imaging. The optimized MRI scan pa-rameters in quantum filter techniques generate contrast in intracellular sodium MR images without using invasive contrast shift agents. Still, validity and clinical utility are in
文摘The temperature and magnetic moment depend-ence for assessing localized heating utilizing a new class of Manganese-Zinc-Gadolinium mag-netic nanoparticles was studied. These particles showed heating effect when subjected to alter-nating filed. Alternatively, a new approach was used to get disperse heating without spot heating by using the synthesis of particles at controlled Curie temperature of less than 44oC. The study reports a simple synthesis of Mn0.5Zn0.5GdxFe(2-x)O4 nanoparticles using chemical co- precipita-tion technique. The particles exhibited Curie temperature of 42篊 and high magnitude of mag-netic moments. The particles showed sigmoid behavior of dependence between temperature and magnetic moments. The Nuclear Magnetic Resonance spectroscopy showed T1 depend-ence on temperature in the range of 10-45篊. The particles may have high promise for self con-trolled magnetic hyperthermia application and its monitoring.
