Since 1978, the University of California San Francisco (UCSF) Ocular Tumor Program has been using particle therapy for treating ocular patients with malignant as well as benign eye disease. Helium ion beams were used ...Since 1978, the University of California San Francisco (UCSF) Ocular Tumor Program has been using particle therapy for treating ocular patients with malignant as well as benign eye disease. Helium ion beams were used initially and were produced by two synchrotron-based systems: first by the 184-inch synchro-cyclotron and later by the Bevalac, at the Lawrence Berkeley National Laboratory (LBNL). Since 1994, protons, produced by a cyclotron-based system at the Crocker Nuclear Laboratory (CNL) Eye Treatment Facility (ETF), have been used for this purpose. The CNL cyclotron produces a 67.5 MeV beam, allowing for a uniquely homogeneous beam for eye treatment, without degradation of the beam or manipulation of the beam line. This paper describes, in detail, the control system for beam delivery, as implemented for measuring and delivering the radiation to ocular tumors at CNL. The control system allows for optimal delivery and rapid termination of the irradiation after the desired dose is achieved. In addition, several safeguard systems are discussed, as these are essential for such a system in the event of failure of software, electronics, or other hardware. The QA analysis shows that the total range of the proton beam is 30.7 ± 1.0 mm in water at iso-center. The beam distal penumbra (80% - 20%) is 1.1 mm for a range-modulated beam at a collimator to iso-center distance of 50 mm. Daily QA checks confirm that the range and modulation is within 0.1 mm. The beam flatness and symmetry in a 25 mm diameter beam are ±1% - 2%. Variation in the daily dosimetry system, as compared to standard dosimetry, is within ±3.5%, with a mean variation of 0.72(±1.9)% and 0.85(±2.3)% for segmented transmission ionization chambers IC1 (upstream) and IC2 (downstream), respectively. From May 1994 to the end of 2015, UCSF has treated 1838 proton ocular patients at the Davis ETF. During this period, no treatments were missed due to any cyclotron or control system failures. The overall performance, maintenance, and quality assurance of the cyclotron and the ocular control system have been excellent.展开更多
BACKGROUND The purpose of this paper is to demonstrate a practical stem cell collection method that provides sufficient stem cells for autologous stem cell transplantation(ASCT)in multiple myeloma(MM)patients despite ...BACKGROUND The purpose of this paper is to demonstrate a practical stem cell collection method that provides sufficient stem cells for autologous stem cell transplantation(ASCT)in multiple myeloma(MM)patients despite low peripheral CD34(pCD34)counts and to describe the benefits of this method for MM patients with limited resources.AIM To demonstrate a practical method for stem cell collection.METHODS Stem cell collection data on the last 300 patients at a community cancer center in Washington were reviewed.We report on the methods of collection,including medi-cations used and timing,used by the blood blank as well as their outcomes.The three MM patients with initially very low pCD34 counts all successfully underwent stem cell collection in a single trip to the transplant center for their ASCT.RESULTS Three patients whose pre-collection pCD34 counts were the lowest and less than 2.5 cells/μL were identified.These patients had the commonality of having multiple barriers to transportation and likely would have been able to make only one trip for the stem cell collections.CONCLUSION Despite particularly low pre-collection peripheral blood CD34 counts,successful autologous stem cell collection in MM patients is feasible by routinely adding plerixafor to granulocyte-colony stimulating factor on day 4 of mobilization.There is limited analysis demonstrating that sufficient stem cells for one or more transplants can be collected using this method.This practical and novel approach may benefit the high number of MM patients who face limited resources,finances,long travel times,and social support.These results are highly relevant to physicians treating similar patients.展开更多
Aim: To clarify the mechanism of the therapeutic action of icariin on erectlile dysfunction (ED). Methods: PDE5 was isolated from the human platelet and PDE4 from the rat liver tissue using the FPLC system (Pharmacia,...Aim: To clarify the mechanism of the therapeutic action of icariin on erectlile dysfunction (ED). Methods: PDE5 was isolated from the human platelet and PDE4 from the rat liver tissue using the FPLC system (Pharmacia, Milton Keynes, UK) and the Mono Q column. The inhibitory effects of icariin on PDE5 and PDE4 activities were investigated by the two-step radioisotope procedure with [3H]-cGMP/[3H]-cAMP. Papaverine served as the control drug. Results: Icariin and papaverine showed dose-dependent inhibitory effects on PDE5 and PDE4 activities. The IC50 of Icariin and papaverine on PDE5 were 0.432 μmol/L and 0.680μmol/L, respectively and those on PDE4, 73.50 μmol/L and 3.07μmol/L, respectively. The potencies of selectivity of icariin and papaverine on PDE5 (PDE4/PDE5 of IC50) were 167.67 times and 4.54 times, respectively. Conclusion: Icariin is a cGMP-specific PDE5 inhibitor that may be developed into an oral effective agent for the treatment of ED.展开更多
AIM To evaluate use of palliative care services in patients with end-stage liver disease who do not have access to liver transplant.METHODS Evaluated were end-stage liver disease patients who were removed from the liv...AIM To evaluate use of palliative care services in patients with end-stage liver disease who do not have access to liver transplant.METHODS Evaluated were end-stage liver disease patients who were removed from the liver transplant wait-list or died prior to transplant at a single transplant center over a 2-year period. Those who were removed due to noncompliance or ultimately transplanted elsewhere were excluded from this study. Patient characteristics associated with palliative care consultation were assessed using logistic regression analysis.RESULTS Six hundred and eighty-three patients were listed for liver transplant in 2013-2014 with 107(16%) dying(n = 62) or removed for clinical decompensation prior to liver transplant(n = 45): Median age was 58 years, and the majority were male(66%), Caucasian(53%), had Child C cirrhosis(61%) or hepatocellular carcinoma(52%). The palliative care team was consulted in only 18 of the 107 patients(17%) who died or were removed, 89% of which occurred as inpatients. Half of these consultations occurred within 72 h of death. In univariable analysis, patients of younger age, white race, and higher end-stage liver disease scores at time of listing and delisting were more likely to receive palliative care services. Only younger age [Odds ratio(OR) = 0.92; P = 0.02] and Caucasian race(OR = 4.90; P = 0.02) were still associated with integration of palliative care services through multivariable analysis.CONCLUSION Palliative care services are grossly underutilized in older, non-white patients with cirrhosis on the liver transplant wait-list. We encourage early integration of these services into clinical decision-making in the transplant population, with further studies aimed at understanding barriers to consultation.展开更多
AIM: To investigate the applications of hydrogen sulfide(H2 S) in eye-specific ailments in mice.METHODS: Heterozygous cystathionine-β-synthase(CBS+/-) and wild-type C57 BL/6 J(WT) mice fed with or without high methio...AIM: To investigate the applications of hydrogen sulfide(H2 S) in eye-specific ailments in mice.METHODS: Heterozygous cystathionine-β-synthase(CBS+/-) and wild-type C57 BL/6 J(WT) mice fed with or without high methionine diet(HMD) were administered either phosphate buffered saline(PBS) or the slow-release H2 S donor: GYY4137. Several analyses were performed to study GYY4137 effects by examining retinal lysates for key protein expressions along with plasma glutamate and glutathione estimations. Intraocular pressure(IOP) was monitored during GYY4137 treatment; barium sulfate and bovine serum albumin conjugated fluorescein isothiocyanate(BSA-FITC) angiographies were performed for examining vasculature and its permeability post-treatment. Visionguided behavior was also tested employing novel object recognition test(NORT) and light-dark box test(LDBT) recordings.RESULTS: CBS deficiency(CBS+/-) coupled with HMD led disruption of methionine/homocysteine(Hcy) metabolism leading to hyperhomocysteinemia(HHcy) in CBS+/-mice as reflected by increased Hcy, and s-adenosylhomocysteine hydrolase(SAHH) levels. Unlike CBS, cystathionine-γ lyase(CSE), methylenetetrahydrofolate reductase(MTHFR) levels which were reduced but compensated by GYY4137intervention. Heightened oxidative and endoplasmic reticulum(ER) stress responses were mitigated by GYY4137 effects along with enhanced glutathione(GSH) levels. Increased glutamate levels in CBS+/-strain were prominent than WT mice and these mice also exhibited higher IOP that was lowered by GYY4137 treatment. CBS deficiency also resulted in vision-guided behavioral impairment as revealed by NORT and LDBT findings. Interestingly, GYY4137 was able to improve CBS+/-mice behavior together with lowering their glutamate levels. Blood-retinal barrier(BRB) appeared compromised in CBS+/-with vessels' leakage that was mitigated in GYY4137 treated group. This corroborated the results for occludin(an integral plasma membrane protein of the cellular tight junctions) stabilization.CONCLUSION: Findings reveal that HHcy-induced glutamate excitotoxicity, oxidative damage, ER-stress and vascular permeability alone or together can compromise ocular health and that GYY4137 could serve as a potential therapeutic agent for treating HHcy induced ocular disorders.展开更多
Anxiety and stress disorders are a major public health issue. However, their pathophysiology is still unclear. The gamma amino acid butyric acid(GABA) neurochemical system has been strongly implicated in their pathoge...Anxiety and stress disorders are a major public health issue. However, their pathophysiology is still unclear. The gamma amino acid butyric acid(GABA) neurochemical system has been strongly implicated in their pathogenesis and treatment by numerous preclinical and clinical studies, the most recent of which have been highlighted and critical review in this paper. Changes in cortical GABA appear related to normal personality styles and responses to stress. While there is accumulating animal and human neuroimaging evidence of cortical and subcortical GABA deficits across a number of anxiety conditions, a clear pattern of findings in specific brain regions for a given disorder is yet to emerge. Neuropsychiatric conditions with anxiety as a clinical feature may have GABA deficits as an underlying feature. Different classes of anxiolytic therapies support GABA function, and this may be an area in which newer GABA neuroimaging techniques could soon offer more personalized therapy. Novel GABAergic pharmacotherapies in development offer potential improvements over current therapies in reducing sedative and physiologic dependency effects, while offering rapid anxiolysis.展开更多
AIM:To assess attitudes and trends regarding the use of high-dose infliximab among pediatric gastroenterologists for treatment of pediatric ulcerative colitis(UC).METHODS:A 19-item survey was distributed to subscriber...AIM:To assess attitudes and trends regarding the use of high-dose infliximab among pediatric gastroenterologists for treatment of pediatric ulcerative colitis(UC).METHODS:A 19-item survey was distributed to subscribers of the pediatric gastroenterology(PEDSGI) listserv.Responses were submitted anonymously and results compiled in a secure website.RESULTS:A total of 113 subscribers(88% based in the United States) responded(101 pediatric gastroenterology attendings and 12 pediatric gastroenterology fellows).There were 46% in academic medical institutions and 39% in hospital-based practices.The majority(91%) were treating >10 patients with UC;13% were treating >100 patients with UC;91% had prescribed infliximab(IFX) 5 mg/kg for UC;72% had prescribed IFX 10 mg/kg for UC.Using a 5-point Likert scale,factors that influenced the decision not to increase IFX dosing in patients with UC included:"improvement on initial dose of IFX"(mean:3.88) and "decision to move to colectomy"(3.69).Lowest mean Likert scores were:"lack of guidelines or literature regarding increased IFX dosing"(1.96) and "insurance authorization or other insurance issues"(2.34)."Insurance authorization or other insurance issues" was identified by 39% as at least somewhat of a factor(Likert score ≥ 3) in their decision not to increase the IFX dose.IFX 10 mg/kg was more commonly used for the treatment of pediatric UC among responders based in the United States(75/100) compared to non-United States responders(6/13,P = 0.047).Induction of remission was reported by 78% of all responders and 81% reported maintenance of remission with IFX 10 mg/kg.One responder reported one death with IFX 10 mg/kg.CONCLUSION:IFX 10 mg/kg is more commonly used in the United States to treat pediatric UC.Efficacy and safety data are required to avoid insurance barriers for its use.展开更多
专栏导读：AME Groups旗下出版了Journal of hToracic Disease （《胸部疾病杂志》）、Annals of Cardiothoracic Surgery （《心胸外科年鉴》）、Chinese Journal of Cancer Research （《中国癌症研究》）和Annals of Translational M...专栏导读：AME Groups旗下出版了Journal of hToracic Disease （《胸部疾病杂志》）、Annals of Cardiothoracic Surgery （《心胸外科年鉴》）、Chinese Journal of Cancer Research （《中国癌症研究》）和Annals of Translational Medicine （《转化医学年鉴》）等近20本英文医学学术期刊。2014年，AME Groups中文平台--“科研时间”的诞生，为广大从事临床和基础研究的科研工作者带来了福音，提供了更多科研交流和学习分享的机会。欢迎广大读者关注我们“AME科研时间专栏”，订阅我们的公众微信号（科研时间：amegroups），给我们提出宝贵的建议和意见，以便于将这个专栏建设得更好，成为读者喜闻乐见的一个栏目。展开更多
Osteoporosis is a highly prevalent public health burden associated with an increased risk of bone fracture, particularly in aging women. Estrogen, an important medicinal component for the preventative and therapeutic ...Osteoporosis is a highly prevalent public health burden associated with an increased risk of bone fracture, particularly in aging women. Estrogen, an important medicinal component for the preventative and therapeutic treatment of postmenopausal osteoporosis, induces osteogenesis by activating the estrogen receptor signaling pathway and upregulating the expression of osteogenic genes, such as bone morphogenetic proteins(BMPs). The epigenetic regulation of estrogen-mediated osteogenesis,however, is still unclear. In this report, we found that estrogen significantly induced the expression of lysine-specific demethylase 6B(KDM6B) and that KDM6B depletion by shRNAs led to a significant reduction in the osteogenic potential of DMSCs.Mechanistically, upon estrogen stimulation, estrogen receptor-α(ERα) was recruited to the KDM6B promoter, directly enhancing KDM6B expression. Subsequently, KDM6B was recruited to the BMP2 and HOXC6 promoters, resulting in the removal of H3K27me3 marks and activating the transcription of BMP2 and HOXC6, the master genes of osteogenic differentiation. Furthermore, we found that estrogen enhanced DMSC osteogenesis during calvarial bone regeneration and that estrogen’s pro-osteogenic effect was dependent on KDM6B in vivo. Taken together, our results demonstrate the vital role of the ERα/KDM6B regulatory axis in the epigenetic regulation of the estrogen-dependent osteogenic response.展开更多
文摘Since 1978, the University of California San Francisco (UCSF) Ocular Tumor Program has been using particle therapy for treating ocular patients with malignant as well as benign eye disease. Helium ion beams were used initially and were produced by two synchrotron-based systems: first by the 184-inch synchro-cyclotron and later by the Bevalac, at the Lawrence Berkeley National Laboratory (LBNL). Since 1994, protons, produced by a cyclotron-based system at the Crocker Nuclear Laboratory (CNL) Eye Treatment Facility (ETF), have been used for this purpose. The CNL cyclotron produces a 67.5 MeV beam, allowing for a uniquely homogeneous beam for eye treatment, without degradation of the beam or manipulation of the beam line. This paper describes, in detail, the control system for beam delivery, as implemented for measuring and delivering the radiation to ocular tumors at CNL. The control system allows for optimal delivery and rapid termination of the irradiation after the desired dose is achieved. In addition, several safeguard systems are discussed, as these are essential for such a system in the event of failure of software, electronics, or other hardware. The QA analysis shows that the total range of the proton beam is 30.7 ± 1.0 mm in water at iso-center. The beam distal penumbra (80% - 20%) is 1.1 mm for a range-modulated beam at a collimator to iso-center distance of 50 mm. Daily QA checks confirm that the range and modulation is within 0.1 mm. The beam flatness and symmetry in a 25 mm diameter beam are ±1% - 2%. Variation in the daily dosimetry system, as compared to standard dosimetry, is within ±3.5%, with a mean variation of 0.72(±1.9)% and 0.85(±2.3)% for segmented transmission ionization chambers IC1 (upstream) and IC2 (downstream), respectively. From May 1994 to the end of 2015, UCSF has treated 1838 proton ocular patients at the Davis ETF. During this period, no treatments were missed due to any cyclotron or control system failures. The overall performance, maintenance, and quality assurance of the cyclotron and the ocular control system have been excellent.
文摘BACKGROUND The purpose of this paper is to demonstrate a practical stem cell collection method that provides sufficient stem cells for autologous stem cell transplantation(ASCT)in multiple myeloma(MM)patients despite low peripheral CD34(pCD34)counts and to describe the benefits of this method for MM patients with limited resources.AIM To demonstrate a practical method for stem cell collection.METHODS Stem cell collection data on the last 300 patients at a community cancer center in Washington were reviewed.We report on the methods of collection,including medi-cations used and timing,used by the blood blank as well as their outcomes.The three MM patients with initially very low pCD34 counts all successfully underwent stem cell collection in a single trip to the transplant center for their ASCT.RESULTS Three patients whose pre-collection pCD34 counts were the lowest and less than 2.5 cells/μL were identified.These patients had the commonality of having multiple barriers to transportation and likely would have been able to make only one trip for the stem cell collections.CONCLUSION Despite particularly low pre-collection peripheral blood CD34 counts,successful autologous stem cell collection in MM patients is feasible by routinely adding plerixafor to granulocyte-colony stimulating factor on day 4 of mobilization.There is limited analysis demonstrating that sufficient stem cells for one or more transplants can be collected using this method.This practical and novel approach may benefit the high number of MM patients who face limited resources,finances,long travel times,and social support.These results are highly relevant to physicians treating similar patients.
文摘Aim: To clarify the mechanism of the therapeutic action of icariin on erectlile dysfunction (ED). Methods: PDE5 was isolated from the human platelet and PDE4 from the rat liver tissue using the FPLC system (Pharmacia, Milton Keynes, UK) and the Mono Q column. The inhibitory effects of icariin on PDE5 and PDE4 activities were investigated by the two-step radioisotope procedure with [3H]-cGMP/[3H]-cAMP. Papaverine served as the control drug. Results: Icariin and papaverine showed dose-dependent inhibitory effects on PDE5 and PDE4 activities. The IC50 of Icariin and papaverine on PDE5 were 0.432 μmol/L and 0.680μmol/L, respectively and those on PDE4, 73.50 μmol/L and 3.07μmol/L, respectively. The potencies of selectivity of icariin and papaverine on PDE5 (PDE4/PDE5 of IC50) were 167.67 times and 4.54 times, respectively. Conclusion: Icariin is a cGMP-specific PDE5 inhibitor that may be developed into an oral effective agent for the treatment of ED.
文摘AIM To evaluate use of palliative care services in patients with end-stage liver disease who do not have access to liver transplant.METHODS Evaluated were end-stage liver disease patients who were removed from the liver transplant wait-list or died prior to transplant at a single transplant center over a 2-year period. Those who were removed due to noncompliance or ultimately transplanted elsewhere were excluded from this study. Patient characteristics associated with palliative care consultation were assessed using logistic regression analysis.RESULTS Six hundred and eighty-three patients were listed for liver transplant in 2013-2014 with 107(16%) dying(n = 62) or removed for clinical decompensation prior to liver transplant(n = 45): Median age was 58 years, and the majority were male(66%), Caucasian(53%), had Child C cirrhosis(61%) or hepatocellular carcinoma(52%). The palliative care team was consulted in only 18 of the 107 patients(17%) who died or were removed, 89% of which occurred as inpatients. Half of these consultations occurred within 72 h of death. In univariable analysis, patients of younger age, white race, and higher end-stage liver disease scores at time of listing and delisting were more likely to receive palliative care services. Only younger age [Odds ratio(OR) = 0.92; P = 0.02] and Caucasian race(OR = 4.90; P = 0.02) were still associated with integration of palliative care services through multivariable analysis.CONCLUSION Palliative care services are grossly underutilized in older, non-white patients with cirrhosis on the liver transplant wait-list. We encourage early integration of these services into clinical decision-making in the transplant population, with further studies aimed at understanding barriers to consultation.
基金Supported by NIH Heart, Lung, and Blood Institute (No.HL-74815)Institute of Neurological Disorders and Stroke (No.NS-084823)
文摘AIM: To investigate the applications of hydrogen sulfide(H2 S) in eye-specific ailments in mice.METHODS: Heterozygous cystathionine-β-synthase(CBS+/-) and wild-type C57 BL/6 J(WT) mice fed with or without high methionine diet(HMD) were administered either phosphate buffered saline(PBS) or the slow-release H2 S donor: GYY4137. Several analyses were performed to study GYY4137 effects by examining retinal lysates for key protein expressions along with plasma glutamate and glutathione estimations. Intraocular pressure(IOP) was monitored during GYY4137 treatment; barium sulfate and bovine serum albumin conjugated fluorescein isothiocyanate(BSA-FITC) angiographies were performed for examining vasculature and its permeability post-treatment. Visionguided behavior was also tested employing novel object recognition test(NORT) and light-dark box test(LDBT) recordings.RESULTS: CBS deficiency(CBS+/-) coupled with HMD led disruption of methionine/homocysteine(Hcy) metabolism leading to hyperhomocysteinemia(HHcy) in CBS+/-mice as reflected by increased Hcy, and s-adenosylhomocysteine hydrolase(SAHH) levels. Unlike CBS, cystathionine-γ lyase(CSE), methylenetetrahydrofolate reductase(MTHFR) levels which were reduced but compensated by GYY4137intervention. Heightened oxidative and endoplasmic reticulum(ER) stress responses were mitigated by GYY4137 effects along with enhanced glutathione(GSH) levels. Increased glutamate levels in CBS+/-strain were prominent than WT mice and these mice also exhibited higher IOP that was lowered by GYY4137 treatment. CBS deficiency also resulted in vision-guided behavioral impairment as revealed by NORT and LDBT findings. Interestingly, GYY4137 was able to improve CBS+/-mice behavior together with lowering their glutamate levels. Blood-retinal barrier(BRB) appeared compromised in CBS+/-with vessels' leakage that was mitigated in GYY4137 treated group. This corroborated the results for occludin(an integral plasma membrane protein of the cellular tight junctions) stabilization.CONCLUSION: Findings reveal that HHcy-induced glutamate excitotoxicity, oxidative damage, ER-stress and vascular permeability alone or together can compromise ocular health and that GYY4137 could serve as a potential therapeutic agent for treating HHcy induced ocular disorders.
文摘Anxiety and stress disorders are a major public health issue. However, their pathophysiology is still unclear. The gamma amino acid butyric acid(GABA) neurochemical system has been strongly implicated in their pathogenesis and treatment by numerous preclinical and clinical studies, the most recent of which have been highlighted and critical review in this paper. Changes in cortical GABA appear related to normal personality styles and responses to stress. While there is accumulating animal and human neuroimaging evidence of cortical and subcortical GABA deficits across a number of anxiety conditions, a clear pattern of findings in specific brain regions for a given disorder is yet to emerge. Neuropsychiatric conditions with anxiety as a clinical feature may have GABA deficits as an underlying feature. Different classes of anxiolytic therapies support GABA function, and this may be an area in which newer GABA neuroimaging techniques could soon offer more personalized therapy. Novel GABAergic pharmacotherapies in development offer potential improvements over current therapies in reducing sedative and physiologic dependency effects, while offering rapid anxiolysis.
基金Supported by DK060617(MBH)DK080825(JMW)+2 种基金DK077734(NG)CCFA Career Development Award(NG)NIH/NCRRUCSF-CTSI Grant,No.UL1 RR024131
文摘AIM:To assess attitudes and trends regarding the use of high-dose infliximab among pediatric gastroenterologists for treatment of pediatric ulcerative colitis(UC).METHODS:A 19-item survey was distributed to subscribers of the pediatric gastroenterology(PEDSGI) listserv.Responses were submitted anonymously and results compiled in a secure website.RESULTS:A total of 113 subscribers(88% based in the United States) responded(101 pediatric gastroenterology attendings and 12 pediatric gastroenterology fellows).There were 46% in academic medical institutions and 39% in hospital-based practices.The majority(91%) were treating >10 patients with UC;13% were treating >100 patients with UC;91% had prescribed infliximab(IFX) 5 mg/kg for UC;72% had prescribed IFX 10 mg/kg for UC.Using a 5-point Likert scale,factors that influenced the decision not to increase IFX dosing in patients with UC included:"improvement on initial dose of IFX"(mean:3.88) and "decision to move to colectomy"(3.69).Lowest mean Likert scores were:"lack of guidelines or literature regarding increased IFX dosing"(1.96) and "insurance authorization or other insurance issues"(2.34)."Insurance authorization or other insurance issues" was identified by 39% as at least somewhat of a factor(Likert score ≥ 3) in their decision not to increase the IFX dose.IFX 10 mg/kg was more commonly used for the treatment of pediatric UC among responders based in the United States(75/100) compared to non-United States responders(6/13,P = 0.047).Induction of remission was reported by 78% of all responders and 81% reported maintenance of remission with IFX 10 mg/kg.One responder reported one death with IFX 10 mg/kg.CONCLUSION:IFX 10 mg/kg is more commonly used in the United States to treat pediatric UC.Efficacy and safety data are required to avoid insurance barriers for its use.
文摘专栏导读：AME Groups旗下出版了Journal of hToracic Disease （《胸部疾病杂志》）、Annals of Cardiothoracic Surgery （《心胸外科年鉴》）、Chinese Journal of Cancer Research （《中国癌症研究》）和Annals of Translational Medicine （《转化医学年鉴》）等近20本英文医学学术期刊。2014年，AME Groups中文平台--“科研时间”的诞生，为广大从事临床和基础研究的科研工作者带来了福音，提供了更多科研交流和学习分享的机会。欢迎广大读者关注我们“AME科研时间专栏”，订阅我们的公众微信号（科研时间：amegroups），给我们提出宝贵的建议和意见，以便于将这个专栏建设得更好，成为读者喜闻乐见的一个栏目。
基金supported by NIH/NIDCR grants K08DE024603, R01DE16513, and R01DE024828
文摘Osteoporosis is a highly prevalent public health burden associated with an increased risk of bone fracture, particularly in aging women. Estrogen, an important medicinal component for the preventative and therapeutic treatment of postmenopausal osteoporosis, induces osteogenesis by activating the estrogen receptor signaling pathway and upregulating the expression of osteogenic genes, such as bone morphogenetic proteins(BMPs). The epigenetic regulation of estrogen-mediated osteogenesis,however, is still unclear. In this report, we found that estrogen significantly induced the expression of lysine-specific demethylase 6B(KDM6B) and that KDM6B depletion by shRNAs led to a significant reduction in the osteogenic potential of DMSCs.Mechanistically, upon estrogen stimulation, estrogen receptor-α(ERα) was recruited to the KDM6B promoter, directly enhancing KDM6B expression. Subsequently, KDM6B was recruited to the BMP2 and HOXC6 promoters, resulting in the removal of H3K27me3 marks and activating the transcription of BMP2 and HOXC6, the master genes of osteogenic differentiation. Furthermore, we found that estrogen enhanced DMSC osteogenesis during calvarial bone regeneration and that estrogen’s pro-osteogenic effect was dependent on KDM6B in vivo. Taken together, our results demonstrate the vital role of the ERα/KDM6B regulatory axis in the epigenetic regulation of the estrogen-dependent osteogenic response.
