The p53 tumor suppressor plays a major role in controlling the initiation and development of cancer by regulating cell cycle arrest,apoptosis,senescence,and DNA repair.The MDM2 oncogene is a major negative regulator o...The p53 tumor suppressor plays a major role in controlling the initiation and development of cancer by regulating cell cycle arrest,apoptosis,senescence,and DNA repair.The MDM2 oncogene is a major negative regulator of p53 that inhibits the activity of p53 and reduces its protein stability.MDM2,p53,and the p53-MDM2 pathway represent welldocumented targets for preventing and/or treating cancer.Natural products,especially those from medicinal and food plants,are a rich source for the discovery and development of novel therapeutic and preventive agents against human cancers.Many natural product-derived MDM2 inhibitors have shown potent efficacy against various human cancers.In contrast to synthetic small-molecule MDM2 inhibitors,the majority of which have been designed to inhibit MDM2-p53 binding and activate p53,many natural product inhibitors directly decrease MDM2 expression and/or MDM2 stability,exerting their anticancer activity in both p53-dependent and p53-independent manners.More recently,several natural products have been reported to target mutant p53 in cancer.Therefore,identification of natural products targeting MDM2,mutant p53,and the p53-MDM2 pathway can provide a promising strategy for the development of novel cancer chemopreventive and chemotherapeutic agents.In this review,we focus our discussion on the recent advances in the discovery and development of anticancer natural products that target the p53-MDM2 pathway,emphasizing several emerging issues,such as the efficacy,mechanism of action,and specificity of these natural products.展开更多
The perception of pain involves the activation of the spinal pathway as well as the supra-spinal pathway,which targets brain regions involved in affective and cognitive processes.Pain and emotions have the capacity to...The perception of pain involves the activation of the spinal pathway as well as the supra-spinal pathway,which targets brain regions involved in affective and cognitive processes.Pain and emotions have the capacity to influence each other reciprocally;negative emotions,such as depression and anxiety,increase the risk for chronic pain,which may lead to anxiety and depression.The amygdala is a key-player in the expression of emotions,receives direct nociceptive information from the parabrachial nucleus,and is densely innervated by noradrenergic brain centers.In recent years,the amygdala has attracted increasing interest for its role in pain perception and modulation.In this review,we will give a short overview of structures involved in the pain pathway,zoom in to afferent and efferent connections to and from the amygdala,with emphasis on the direct parabrachio-amygdaloid pathway and discuss the evidence for amygdala’s role in pain processing and modulation.In addition to the involvement of the amygdala in negative emotions during the perception of pain,this brain structure is also a target site for many neuromodulators to regulate the perception of pain.We will end this article with a short review on the effects of noradrenaline and its role in hypoalgesia and analgesia.展开更多
Technology can be used to supplement healthcare provider diabetes care by providing both educational and motivational support. Education can be provided using technology allowing patients to learn new practices and ro...Technology can be used to supplement healthcare provider diabetes care by providing both educational and motivational support. Education can be provided using technology allowing patients to learn new practices and routines related to diabetes management. Technology can support daily diabetes self-management activities including blood glucose monitoring, exercising, healthy eating, taking medication, monitoring for complications, and problem-solving. This article describes an integrative review conducted to evaluate the types of technology being used to facilitate diabetes self-management and the effect of that technology on self-management and diabetes outcomes for adults living with type 2 diabetes mellitus. A literature review was conducted by searching Medline, Pub Med, and Psych INFO databases using the search terms: diabetes self-management, technology, type 2 diabetes, smartphones, cell phones, and diabetes mellitus covering the years from 2008-2013. Articles relying on secondary data(editorials, systematic reviews) and articles describing study protocol only were excluded. Fourteen studies including qualitative, quasiexperimental, and randomized controlled trial designs were identified and included in the review. The review found that technological interventions had positive impacts on diabetes outcomes including improvements in hemoglobin A1 C levels, diabetes self-management behaviors, and diabetes self-efficacy. Results indicate that technological interventions can benefit people living with diabetes when used in conjunction with diabetes care delivered by healthcare providers.展开更多
Data visualization technique was applied to analyze the daily QA results of photon and electron beams. Special attention was paid to any trend the beams might display. A Varian Trilogy Linac equipped with dual photon ...Data visualization technique was applied to analyze the daily QA results of photon and electron beams. Special attention was paid to any trend the beams might display. A Varian Trilogy Linac equipped with dual photon energies and five electron energies was commissioned in early 2010. Daily Linac QA tests including the output constancy, beam flatness and symmetry (radial and transverse directions) were performed with an ionization chamber array device (QA Beam Checker Plus, Standard Imaging). The data of five years were collected and analyzed. For each energy, the measured data were exported and processed for visual trending using an in-house Matlab program. These daily data were cross-correlated with the monthly QA and annual QA results, as well as the preventive maintenance records. Majority of the output were within 1% of variation, with a consistent positive/upward drift for all seven energies (^+0.25% per month). The baseline of daily device is reset annually right after the TG-51 calibration. This results in a sudden drop of the output. On the other hand, the large amount of data using the same baseline exhibits a sinusoidal behavior (period = 12 months;amplitude = 0.8%, 0.5% for photons, electrons, respectively) on symmetry and flatness when normalization of baselines is accounted for. The well known phenomenon of new Linac output drift was clearly displayed. This output drift was a result of the air leakage of the over-pressurized sealed monitor chambers for the specific vendor. Data visualization is a new trend in the era of big data in radiation oncology research. It allows the data to be displayed visually and therefore more intuitive. Based on the visual display from the past, the physicist might predict the trend of the Linac and take actions proactively. It also makes comparisons, alerts failures, and potentially identifies causalities.展开更多
BACKGROUND With an ongoing demand for transplantable organs,optimization of donor management protocols,specifically in trauma populations,is important for obta-ining a high yield of viable organs per patient.Endocrine...BACKGROUND With an ongoing demand for transplantable organs,optimization of donor management protocols,specifically in trauma populations,is important for obta-ining a high yield of viable organs per patient.Endocrine management of brain-dead potential organ donors(BPODs)is controversial,leading to heterogeneous clinical management approaches.Previous studies have shown that when levo-thyroxine was combined with other treatments,including steroids,vasopressin,and insulin,BPODs had better organ recovery and survival outcomes were increased for transplant recipients.AIM To determine if levothyroxine use in combination with steroids in BPODs increased the number of organs donated in trauma patients.METHODS A retrospective review of adult BPODs from a single level 1 trauma center over ten years was performed.Exclusion criteria included patients who were not solid organ donors,patients who were not declared brain dead(donation after circulatory death),and patients who did not receive steroids in their hospital course.Levothyroxine and steroid administration,the number of organs donated,the types of organs donated,and demographic information were recorded.Univariate analyses were performed with P<0.05 considered to be statistically significant.RESULTS A total of 88 patients met inclusion criteria,69(78%)of whom received levothyroxine and steroids(ST/LT group)vs 19(22%)receiving steroids without levothyroxine(ST group).No differences were observed between the groups for gender,race,pertinent injury factors,age,or other hormone therapies used(P>0.05).In the ST/LT group,68.1%(n=47)donated a high yield(3-5)of organ types per donor compared to 42.1%(n=8)in the ST group(P=0.038).There was no difference in the total number of organ types donated between the groups(P=0.068).CONCLUSION This study suggests that combining levothyroxine and steroid administration increases high-yield organ donation per donor in BPODs in the trauma patient population.Limitations to this study include the retrospective design and the relatively smal展开更多
Agricultural practices currently contribute to the emission of approximately 10%–12%atmospheric greenhouse gasses,with tillage agriculture accelerating soil disruption and carbon dioxide release.Nevertheless,various ...Agricultural practices currently contribute to the emission of approximately 10%–12%atmospheric greenhouse gasses,with tillage agriculture accelerating soil disruption and carbon dioxide release.Nevertheless,various options exist,such as converting new lands for agriculture,promoting healthier plant-based diets,adopting advanced management technologies,and minimizing food loss.However,these measures alone are insufficient to ensure environmental sustainability within planetary boundaries.展开更多
The first demonstration of laser action in ruby was made in 1960 by T.H.Maiman of Hughes Research Laboratories,USA.Many laboratories worldwide began the search for lasers using different materials,operating at differe...The first demonstration of laser action in ruby was made in 1960 by T.H.Maiman of Hughes Research Laboratories,USA.Many laboratories worldwide began the search for lasers using different materials,operating at different wavelengths.In the UK,academia,industry and the central laboratories took up the challenge from the earliest days to develop these systems for a broad range of applications.This historical review looks at the contribution the UK has made to the advancement of the technology,the development of systems and components and their exploitation over the last 60 years.展开更多
基金supported by National Institutes of Health(NIH)/National Cancer Institute(NCI)grants(R01 CA186662 and R01 CA214019 to RZ).The content is solely the responsibility of the authors,and does not necessarily represent the official views of the National Institutes of Health.supported by American Cancer Society(ACS)grant RSG-15-009-01-CDDsupported by funds for the Robert L.Boblitt Endowed Professor in Drug Discovery and research funds from the College of Pharmacy and the University of Houston+3 种基金supported by grants from the National Nature Science Foundation(81630086,81427805,81672763,31401611,and 81502122)the Key Research Program(ZDRW-ZS-2017-1)the Strategic Priority Research Program(XDA12020319)of the Chinese Academy of Sciencesthe Science and Technology Commission of Shanghai Municipality(16391903700 and 14391901800).
文摘The p53 tumor suppressor plays a major role in controlling the initiation and development of cancer by regulating cell cycle arrest,apoptosis,senescence,and DNA repair.The MDM2 oncogene is a major negative regulator of p53 that inhibits the activity of p53 and reduces its protein stability.MDM2,p53,and the p53-MDM2 pathway represent welldocumented targets for preventing and/or treating cancer.Natural products,especially those from medicinal and food plants,are a rich source for the discovery and development of novel therapeutic and preventive agents against human cancers.Many natural product-derived MDM2 inhibitors have shown potent efficacy against various human cancers.In contrast to synthetic small-molecule MDM2 inhibitors,the majority of which have been designed to inhibit MDM2-p53 binding and activate p53,many natural product inhibitors directly decrease MDM2 expression and/or MDM2 stability,exerting their anticancer activity in both p53-dependent and p53-independent manners.More recently,several natural products have been reported to target mutant p53 in cancer.Therefore,identification of natural products targeting MDM2,mutant p53,and the p53-MDM2 pathway can provide a promising strategy for the development of novel cancer chemopreventive and chemotherapeutic agents.In this review,we focus our discussion on the recent advances in the discovery and development of anticancer natural products that target the p53-MDM2 pathway,emphasizing several emerging issues,such as the efficacy,mechanism of action,and specificity of these natural products.
文摘The perception of pain involves the activation of the spinal pathway as well as the supra-spinal pathway,which targets brain regions involved in affective and cognitive processes.Pain and emotions have the capacity to influence each other reciprocally;negative emotions,such as depression and anxiety,increase the risk for chronic pain,which may lead to anxiety and depression.The amygdala is a key-player in the expression of emotions,receives direct nociceptive information from the parabrachial nucleus,and is densely innervated by noradrenergic brain centers.In recent years,the amygdala has attracted increasing interest for its role in pain perception and modulation.In this review,we will give a short overview of structures involved in the pain pathway,zoom in to afferent and efferent connections to and from the amygdala,with emphasis on the direct parabrachio-amygdaloid pathway and discuss the evidence for amygdala’s role in pain processing and modulation.In addition to the involvement of the amygdala in negative emotions during the perception of pain,this brain structure is also a target site for many neuromodulators to regulate the perception of pain.We will end this article with a short review on the effects of noradrenaline and its role in hypoalgesia and analgesia.
文摘Technology can be used to supplement healthcare provider diabetes care by providing both educational and motivational support. Education can be provided using technology allowing patients to learn new practices and routines related to diabetes management. Technology can support daily diabetes self-management activities including blood glucose monitoring, exercising, healthy eating, taking medication, monitoring for complications, and problem-solving. This article describes an integrative review conducted to evaluate the types of technology being used to facilitate diabetes self-management and the effect of that technology on self-management and diabetes outcomes for adults living with type 2 diabetes mellitus. A literature review was conducted by searching Medline, Pub Med, and Psych INFO databases using the search terms: diabetes self-management, technology, type 2 diabetes, smartphones, cell phones, and diabetes mellitus covering the years from 2008-2013. Articles relying on secondary data(editorials, systematic reviews) and articles describing study protocol only were excluded. Fourteen studies including qualitative, quasiexperimental, and randomized controlled trial designs were identified and included in the review. The review found that technological interventions had positive impacts on diabetes outcomes including improvements in hemoglobin A1 C levels, diabetes self-management behaviors, and diabetes self-efficacy. Results indicate that technological interventions can benefit people living with diabetes when used in conjunction with diabetes care delivered by healthcare providers.
文摘Data visualization technique was applied to analyze the daily QA results of photon and electron beams. Special attention was paid to any trend the beams might display. A Varian Trilogy Linac equipped with dual photon energies and five electron energies was commissioned in early 2010. Daily Linac QA tests including the output constancy, beam flatness and symmetry (radial and transverse directions) were performed with an ionization chamber array device (QA Beam Checker Plus, Standard Imaging). The data of five years were collected and analyzed. For each energy, the measured data were exported and processed for visual trending using an in-house Matlab program. These daily data were cross-correlated with the monthly QA and annual QA results, as well as the preventive maintenance records. Majority of the output were within 1% of variation, with a consistent positive/upward drift for all seven energies (^+0.25% per month). The baseline of daily device is reset annually right after the TG-51 calibration. This results in a sudden drop of the output. On the other hand, the large amount of data using the same baseline exhibits a sinusoidal behavior (period = 12 months;amplitude = 0.8%, 0.5% for photons, electrons, respectively) on symmetry and flatness when normalization of baselines is accounted for. The well known phenomenon of new Linac output drift was clearly displayed. This output drift was a result of the air leakage of the over-pressurized sealed monitor chambers for the specific vendor. Data visualization is a new trend in the era of big data in radiation oncology research. It allows the data to be displayed visually and therefore more intuitive. Based on the visual display from the past, the physicist might predict the trend of the Linac and take actions proactively. It also makes comparisons, alerts failures, and potentially identifies causalities.
文摘BACKGROUND With an ongoing demand for transplantable organs,optimization of donor management protocols,specifically in trauma populations,is important for obta-ining a high yield of viable organs per patient.Endocrine management of brain-dead potential organ donors(BPODs)is controversial,leading to heterogeneous clinical management approaches.Previous studies have shown that when levo-thyroxine was combined with other treatments,including steroids,vasopressin,and insulin,BPODs had better organ recovery and survival outcomes were increased for transplant recipients.AIM To determine if levothyroxine use in combination with steroids in BPODs increased the number of organs donated in trauma patients.METHODS A retrospective review of adult BPODs from a single level 1 trauma center over ten years was performed.Exclusion criteria included patients who were not solid organ donors,patients who were not declared brain dead(donation after circulatory death),and patients who did not receive steroids in their hospital course.Levothyroxine and steroid administration,the number of organs donated,the types of organs donated,and demographic information were recorded.Univariate analyses were performed with P<0.05 considered to be statistically significant.RESULTS A total of 88 patients met inclusion criteria,69(78%)of whom received levothyroxine and steroids(ST/LT group)vs 19(22%)receiving steroids without levothyroxine(ST group).No differences were observed between the groups for gender,race,pertinent injury factors,age,or other hormone therapies used(P>0.05).In the ST/LT group,68.1%(n=47)donated a high yield(3-5)of organ types per donor compared to 42.1%(n=8)in the ST group(P=0.038).There was no difference in the total number of organ types donated between the groups(P=0.068).CONCLUSION This study suggests that combining levothyroxine and steroid administration increases high-yield organ donation per donor in BPODs in the trauma patient population.Limitations to this study include the retrospective design and the relatively smal
文摘Agricultural practices currently contribute to the emission of approximately 10%–12%atmospheric greenhouse gasses,with tillage agriculture accelerating soil disruption and carbon dioxide release.Nevertheless,various options exist,such as converting new lands for agriculture,promoting healthier plant-based diets,adopting advanced management technologies,and minimizing food loss.However,these measures alone are insufficient to ensure environmental sustainability within planetary boundaries.
文摘The first demonstration of laser action in ruby was made in 1960 by T.H.Maiman of Hughes Research Laboratories,USA.Many laboratories worldwide began the search for lasers using different materials,operating at different wavelengths.In the UK,academia,industry and the central laboratories took up the challenge from the earliest days to develop these systems for a broad range of applications.This historical review looks at the contribution the UK has made to the advancement of the technology,the development of systems and components and their exploitation over the last 60 years.
