A human K562 leukaemia call and acute adult leudaemia patient samples have been used to test the efficacy of antineoplastic agents with MTT assay.All 18 drugs were invoved.According to the purpose of experiment these...A human K562 leukaemia call and acute adult leudaemia patient samples have been used to test the efficacy of antineoplastic agents with MTT assay.All 18 drugs were invoved.According to the purpose of experiment these durgs were applied at different opportunities or combinations.The drug efficacy has been observed and summarized as four different conditions:1.the change of the time(△ T )closely related with drug effacacy, during the duration the change of drug concentration(△ C) at certain extent has almost no influence; 2the △ C closely related with the efficacy, the △ T has no influence;3. The △ C and △ T effect the results together;and 4.the △ C and △ T effect not the result. And then draw a conclution that the process or drug effacacy has a multiple function with flat distrtct.展开更多
Antineoplastic agent and contrast medium were injected into transplanted tumors of mice under guidance with CT, site and range of the intratumoural drug were shown on CT image immediately. It was value of multipoint i...Antineoplastic agent and contrast medium were injected into transplanted tumors of mice under guidance with CT, site and range of the intratumoural drug were shown on CT image immediately. It was value of multipoint injections, concentration of 0.1 mg/0.l ml MMC every point, 1 cm interval of injection. After the injections, the tumor size of mice reduced and at last disappeared (ratio of inhibited tumor 59.32% in 0.05 mg MMC group, 43.86% in 0.1 mg MMC group).The pathologic examination showed coagulatic necrosis of the tumor tissues. The higher concentration of antineoplastic agent (0.2 mg MMC) could make the tumors enlarged (ratio of inhibited tumor -15.3%). The tissues and vessels around the tumors were not injured, if MMC overflow out off the tumor.展开更多
Objective:To evaluate the in vitro anticancer activity of crude ethyl acetate extracts of the culture of four marine-derived fungi Aspergillus similanensis KUFA 0013(E1),Neosartorya paulistemis KUFC 7897(E2),Neosartor...Objective:To evaluate the in vitro anticancer activity of crude ethyl acetate extracts of the culture of four marine-derived fungi Aspergillus similanensis KUFA 0013(E1),Neosartorya paulistemis KUFC 7897(E2),Neosartorya siamensis KUFA 0017(E4) and Talaromyces trachyspermus KUFC 0021(E3) on a panel of seven human cancer cell lines.Methods:Effects on cell proliferation,induction of DNA damage and cell death were assessed by MTT and clonogenic assays,comet assay and nuclear condensation assay,respectively.Results:The proliferation of HepG2,HCTl 16 and A375 cells decreased after incubation with the extracts E2 and E4.The anti-proliterative effect was confirmed by morphologic alterations and by clonogenic assay.Both extracts also induced cell death in HepG2 and HCT116 cells.Doxorubicin was used as a positive control and showed in vitro anticancer activity.Conclusions:This study demonstrated,for the first time,that extracts of Neosartorya paulistensis and Neosartorya siamensis have selective anti-proliferative and cell death activities in HepG2,HCT16 and A375 cells.The bioactivity of these extracts suggests a potential for biotechnological applications and substantiates that both should be further considered for the elucidation of the molecular targets and signal transduction pathways involved.展开更多
Background: Non-invasive facial treatments have the ability to rejuvenate the facial profile when specific pharmacologic agents and modalities are prescribed and used in combination taking into consideration each pati...Background: Non-invasive facial treatments have the ability to rejuvenate the facial profile when specific pharmacologic agents and modalities are prescribed and used in combination taking into consideration each patient’s unique skin type and condition. RATIONALE Epinova is a non-invasive skin treatment that combines the correct concentrations and combinations of topicals and modalities to elicit facial rejuvenation with no down-time or side effects. Purpose: This paper focuses on facial rejuvenation improvements combining the RATIONALE Essential Six skincare system (RATIONALE, Victoria, Australia) to protect and repair the skin with the RATIONALE Epinova facial treatment every 4-6 weeks—which uses non-invasive technologies and professional strength active ingredients to deliver visible changes to skin tone and texture. Methods: Subjects underwent a RATIONALE consultation, including taking a skin history and skin imaging, followed by a data analysis and diagnosis of skin condition and prescription of a customized RATIONALE treatement (Epinova), including appropriate pharmacologic agents and treatment with personalized photo/sono therapeutic devices. Results: Subjects reported increased skin hydration, tactile improvements, skin firmness and visible radiance following the RATIONALE Epinova treatment. Further investigations will be initiated to explore the potential for longer term improvements, including connenctive tissue deposition, reduction of erythema etc. Treatments should be performed every 4-6 weeks for patients under 40 and every 3-4 weeks for patients over 40, to support cell differentiation, migration and desquamation to achieve non-invasive facial rejuvenation. Conclusion: This study demonstrated that the synergy of pharmacologic, LED light therapy and ultrasonic technologies when prescribed and administered by a trained skin therapist, can lead to a visible improvement in the signs of facial ageing and photodamage, restoring the appearance of healthy, radiant skin. .展开更多
目的探讨安罗替尼相关高血压的临床特点。方法检索中国知网、万方、PubMed、Web of Science数据库(截至2023年7月31日),收集安罗替尼相关高血压文献病例报告类文献,提取患者基本情况、安罗替尼用药情况、高血压情况、干预措施和转归等,...目的探讨安罗替尼相关高血压的临床特点。方法检索中国知网、万方、PubMed、Web of Science数据库(截至2023年7月31日),收集安罗替尼相关高血压文献病例报告类文献,提取患者基本情况、安罗替尼用药情况、高血压情况、干预措施和转归等,进行描述性统计分析。结果纳入分析的文献为16篇,患者18例,男性8例,女性10例;年龄27~76岁,平均58岁;非小细胞肺癌13例,结缔组织和软组织恶性肿瘤2例,肝内胆管癌1例,卵巢癌1例,子宫癌1例。联用其他抗肿瘤药物4例;安罗替尼初始剂量均为12 mg/d。发生的高血压分级为1级3例(17%),2级4例(22%),3级9例(50%),4级2例(11%)。除8例患者从服用安罗替尼至发生高血压的时间不详外,其余10例患者从服用安罗替尼至发生高血压的时间在7 d~6个月内,中位时间36(30,42)d,其中7例(39%)发生在服用安罗替尼2个月内。18例患者中出现不同程度乏力6例(33%),头痛6例(33%),头晕5例(28%),呕吐3例(17%),视物模糊2例(11%),恶心1例(6%),抽搐1例(6%)。13例伴其他不良反应,其中手足综合征7例(39%),蛋白尿3例(17%),高脂血症3例(17%),可逆性后部白质脑病综合征2例(11%),癫痫1例(6%),便血1例(6%),皮疹1例(6%)。1~2级患者安罗替尼未调整(6例)或减量治疗(1例)后耐受良好;3~4级患者中,8例停用安罗替尼且接受降压药治疗,2例减量治疗,1例未调整,随访血压控制平稳。结论安罗替尼相关高血压多发生在用药2个月内,往往伴其他不良反应,3级以上高血压常见,但大多数患者经对症处理、停药或减量后转归良好。展开更多
BACKGROUND Small cell lung cancer(SCLC)is a common and aggressive subtype of lung cancer.It is characterized by rapid growth and a high mortality rate.Approximately 10%of patients with SCLC present with brain metastas...BACKGROUND Small cell lung cancer(SCLC)is a common and aggressive subtype of lung cancer.It is characterized by rapid growth and a high mortality rate.Approximately 10%of patients with SCLC present with brain metastases at the time of diagnosis,which is associated with a median survival of 5 mo.This study aimed to summarize the effect of bevacizumab on the progression-free survival(PFS)and overall survival of patients with brain metastasis of SCLC.CASE SUMMARY A 62-year-old man was referred to our hospital in February 2023 because of dizziness and numbness of the right lower extremity without headache or fever for more than four weeks.The patient was diagnosed with limited-stage SCLC.He received 8 cycles of chemotherapy combined with maintenance bevacizumab therapy and achieved a PFS of over 7 mo.CONCLUSION The combination of bevacizumab and irinotecan effectively alleviated brain metastasis in SCLC and prolonged PFS.展开更多
目的:基于网络药理学方法筛选固本平喘剂(补骨脂、地龙、防风)中的主要活性成分,探讨其治疗支气管哮喘的作用机制。方法:通过中药系统药理学数据库TCMSP数据库、中药与化学成分数据库,筛选固本平喘剂的活性成分及靶标。利用Genecards、O...目的:基于网络药理学方法筛选固本平喘剂(补骨脂、地龙、防风)中的主要活性成分,探讨其治疗支气管哮喘的作用机制。方法:通过中药系统药理学数据库TCMSP数据库、中药与化学成分数据库,筛选固本平喘剂的活性成分及靶标。利用Genecards、OMIM数据库获得支气管哮喘的潜在靶标基因。将两者靶基因进行映射后通过Cytoscape3.6.1软件构建“成分-靶标”网络、结合String数据库构建蛋白质相互作用网络扩充核心靶点。依托功能注释生物信息学分析平台DAVID数据库对固本平喘剂的作用靶点进行基因本体(gene ontology,GO)生物学过程和基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)通路富集注释分析,通过Autodock vina软件进行分子对接以验证结果。结果:符合筛选条件的共有53个活性成分,补骨脂18个,地龙17个,防风18个,筛选得到固本平喘剂关键成分,包括补骨脂黄酮类、补骨脂查耳酮类、汉黄芩素、补骨脂酚、β-谷甾醇等;通过GenCards、OMIM数据库剔除重复后,共收集支气管哮喘潜在靶点2358个。将固本平喘剂和支气管哮喘靶点进行映射取交集共得到237个交叉靶点,即固本平喘剂治疗支气管哮喘潜在作用靶点。以degree值大于二倍均值的靶点为PTGS2、ESR1、ACHE、ESR2、PTGS1、DPP4、ADORA3,degree值排名前5的靶蛋白为PIK3CA、MAPK3、MAPK1、TP53、AKT1。主要涉及PI3K-Akt信号通路、TNF信号通路、趋化因子信号通路、FoxO信号通路、MAPK信号通路、Toll样受体信号通路、T细胞受体信号通路等。结论:固本平喘剂治疗支气管哮喘潜在作用靶点有PTGS2、ESR1、ACHE、ESR2、PTGS1、DPP4、ADORA3、PIK3CA、MAPK3、MAPK1、TP53、AKT1,可能通过抗感染、调节免疫、抑制气道重塑等发挥作用。展开更多
Multiple sclerosis(MS)is an inflammatory demyelinating disease of the central nervous system.The disability caused by inflammatory demyelination clinically dominates the early stages of relapsing-remitting MS and is r...Multiple sclerosis(MS)is an inflammatory demyelinating disease of the central nervous system.The disability caused by inflammatory demyelination clinically dominates the early stages of relapsing-remitting MS and is reversible.Once there is considerable loss of axons,MS patients enter a secondary progressive stage.Disease-modifying drugs currently in use for MS suppress the immune system and reduce relapse rates but are not effective in the progressive stage.Various animal models of MS(mostly mouse and rat)have been established and proved useful in studying the disease process and response to therapy.The experimental autoimmune encephalomyelitis animal studies reviewed here showed that a chronic progressive disease can be induced by immunization with appropriate amounts of myelin oligodendrocyte glycoprotein together with mycobacterium tuberculosis and pertussis toxin in Freund's adjuvant.The clinical manifestations of autoimmune encephalomyelitis disease were prevented or reduced by treatment with certain pharmacological agents given prior to,at,or after peak disease,and the agents had protective effects as shown by inhibiting demyelination and damage to neurons,axons and oligodendrocytes.In the cuprizone-induced toxicity animal studies,the pharmacological agents tested were able to promote remyelination and increase the number of oligodendrocytes when administered therapeutically or prophylactically.A monoclonal IgM antibody protected axons in the spinal cord and preserved motor function in animals inoculated with Theiler's murine encephalomyelitis virus.In all these studies the pharmacological agents were administered singly.A combination therapy may be more effective,especially using agents that target neuroinflammation and neurodegeneration,as they may exert synergistic actions.展开更多
Parkinson’s disease (PD) or Paralysis Agitans was first formally described in “An essay on the shaking palsy”, published in 1817 by a British physician named James Parkinson. In the late 1950’s, dopamine was relat...Parkinson’s disease (PD) or Paralysis Agitans was first formally described in “An essay on the shaking palsy”, published in 1817 by a British physician named James Parkinson. In the late 1950’s, dopamine was related with the function of the corpus striatum, thus with the control of motor function. But it was not until 1967, when the landmark study of George C. Cotzias, demonstrated that oral L-DOPA, the precursor of dopamine metabolism, was shown to induce remission of PD symptoms, that the definitive association between the two was firmly established. However, later on L-DOPA treatment began to show a loss of effectiveness and demonstrated to induce a variety of undesirable effects, the most prominent being diskinesia. As a result of this, a variety of alternative or complementary pharmacological strategies have been developed. In this chapter we review the wide variety of strategies that have been used through time, which are geared toward reducing the most disabling symptoms of PD. We additionally make some suggestions as to which are the most promising ones.展开更多
宫颈神经内分泌癌(neuroendocrine carcinoma of the cervix,NECC)是一种罕见的恶性程度极高的妇科肿瘤。临床上对NECC的组织来源、发病机制并不明确。NECC没有标准的治疗方案,多是结合宫颈鳞状细胞癌、腺癌和小细胞肺癌的治疗经验制定...宫颈神经内分泌癌(neuroendocrine carcinoma of the cervix,NECC)是一种罕见的恶性程度极高的妇科肿瘤。临床上对NECC的组织来源、发病机制并不明确。NECC没有标准的治疗方案,多是结合宫颈鳞状细胞癌、腺癌和小细胞肺癌的治疗经验制定治疗方案。近年来大样本队列基因组研究显示,NECC与宫颈外神经内分泌癌具有不同的基因组学特征,对NECC与宫颈外神经内分泌癌之间的生物学和治疗相关性提出了质疑。由于NECC的罕见性,获得足够数量的患者进行疗效试验的可能性很低,这阻碍了NECC标准治疗方案的制定。基因检测能为NECC靶向药物的个体化治疗提供策略。多项研究结果显示,NECC具有潜在的可调控的治疗靶点,免疫疗法与放射疗法结合可以延长晚期复发性NECC患者的长期生存。综述NECC的分子特征、靶向药物及免疫治疗的研究进展。展开更多
他汀类药物是3-羟基-3-甲基戊二酰辅酶A还原酶(3-hydroxy-3-methylglutaryl-coenzyme A reductase,HMGCR)抑制剂,可通过减少胆固醇生物合成和诱导低密度脂蛋白受体表达而降低血浆胆固醇水平,广泛应用于高脂血症的治疗和心脑血管疾病的预...他汀类药物是3-羟基-3-甲基戊二酰辅酶A还原酶(3-hydroxy-3-methylglutaryl-coenzyme A reductase,HMGCR)抑制剂,可通过减少胆固醇生物合成和诱导低密度脂蛋白受体表达而降低血浆胆固醇水平,广泛应用于高脂血症的治疗和心脑血管疾病的预防;此外,他汀类药物可能通过阻断细胞周期进展、诱导细胞凋亡、抑制血管生成、抑制肿瘤生长和转移而具有潜在的抗癌作用。卵巢癌预后较差,给患者造成了严重的经济和心理负担。他汀类药物通过抑制甲羟戊酸(mevalonic acid,MVA)途径、促进铁死亡、调节细胞自噬和调节肿瘤微环境(tumor microenvironment,TME)等多种途径发挥抗肿瘤作用和改善卵巢癌化疗耐药现象,同时在某种程度上可抑制卵巢癌细胞增殖,降低卵巢癌患病风险,改善预后,协同并增强化疗药物抗肿瘤作用,降低复发率。综述他汀类药物在卵巢癌的预防和治疗中的研究新进展,以期对未来临床实践提供帮助。展开更多
文摘A human K562 leukaemia call and acute adult leudaemia patient samples have been used to test the efficacy of antineoplastic agents with MTT assay.All 18 drugs were invoved.According to the purpose of experiment these durgs were applied at different opportunities or combinations.The drug efficacy has been observed and summarized as four different conditions:1.the change of the time(△ T )closely related with drug effacacy, during the duration the change of drug concentration(△ C) at certain extent has almost no influence; 2the △ C closely related with the efficacy, the △ T has no influence;3. The △ C and △ T effect the results together;and 4.the △ C and △ T effect not the result. And then draw a conclution that the process or drug effacacy has a multiple function with flat distrtct.
文摘Antineoplastic agent and contrast medium were injected into transplanted tumors of mice under guidance with CT, site and range of the intratumoural drug were shown on CT image immediately. It was value of multipoint injections, concentration of 0.1 mg/0.l ml MMC every point, 1 cm interval of injection. After the injections, the tumor size of mice reduced and at last disappeared (ratio of inhibited tumor 59.32% in 0.05 mg MMC group, 43.86% in 0.1 mg MMC group).The pathologic examination showed coagulatic necrosis of the tumor tissues. The higher concentration of antineoplastic agent (0.2 mg MMC) could make the tumors enlarged (ratio of inhibited tumor -15.3%). The tissues and vessels around the tumors were not injured, if MMC overflow out off the tumor.
基金supported by project MARBIOTECH,grant NORTE-07-0124-FEDER-000047-BPD-2013-06partially funded by project MARBIOTECH(reference NORTE-070124-FEDER-000047)+6 种基金co-financed by the North Portugal Regional Operational Programme(ON.2-O Novo Norte)the National Strategic Reference Framework(NSRF)the European Regional Development Fund(ERDF)the ERDF,through the Competitiveness and TradeExpansion Program(COMPETE)national funds provided by the Foundation for Science and Technology(FCT)project PEst-C/MARL-1A0015/2013the financial aid provided by the Master of Marine Sciences-Marine Recourses,of the Institute of Biomedical Sciences Abel Salazar,University of Porto
文摘Objective:To evaluate the in vitro anticancer activity of crude ethyl acetate extracts of the culture of four marine-derived fungi Aspergillus similanensis KUFA 0013(E1),Neosartorya paulistemis KUFC 7897(E2),Neosartorya siamensis KUFA 0017(E4) and Talaromyces trachyspermus KUFC 0021(E3) on a panel of seven human cancer cell lines.Methods:Effects on cell proliferation,induction of DNA damage and cell death were assessed by MTT and clonogenic assays,comet assay and nuclear condensation assay,respectively.Results:The proliferation of HepG2,HCTl 16 and A375 cells decreased after incubation with the extracts E2 and E4.The anti-proliterative effect was confirmed by morphologic alterations and by clonogenic assay.Both extracts also induced cell death in HepG2 and HCT116 cells.Doxorubicin was used as a positive control and showed in vitro anticancer activity.Conclusions:This study demonstrated,for the first time,that extracts of Neosartorya paulistensis and Neosartorya siamensis have selective anti-proliferative and cell death activities in HepG2,HCT16 and A375 cells.The bioactivity of these extracts suggests a potential for biotechnological applications and substantiates that both should be further considered for the elucidation of the molecular targets and signal transduction pathways involved.
文摘Background: Non-invasive facial treatments have the ability to rejuvenate the facial profile when specific pharmacologic agents and modalities are prescribed and used in combination taking into consideration each patient’s unique skin type and condition. RATIONALE Epinova is a non-invasive skin treatment that combines the correct concentrations and combinations of topicals and modalities to elicit facial rejuvenation with no down-time or side effects. Purpose: This paper focuses on facial rejuvenation improvements combining the RATIONALE Essential Six skincare system (RATIONALE, Victoria, Australia) to protect and repair the skin with the RATIONALE Epinova facial treatment every 4-6 weeks—which uses non-invasive technologies and professional strength active ingredients to deliver visible changes to skin tone and texture. Methods: Subjects underwent a RATIONALE consultation, including taking a skin history and skin imaging, followed by a data analysis and diagnosis of skin condition and prescription of a customized RATIONALE treatement (Epinova), including appropriate pharmacologic agents and treatment with personalized photo/sono therapeutic devices. Results: Subjects reported increased skin hydration, tactile improvements, skin firmness and visible radiance following the RATIONALE Epinova treatment. Further investigations will be initiated to explore the potential for longer term improvements, including connenctive tissue deposition, reduction of erythema etc. Treatments should be performed every 4-6 weeks for patients under 40 and every 3-4 weeks for patients over 40, to support cell differentiation, migration and desquamation to achieve non-invasive facial rejuvenation. Conclusion: This study demonstrated that the synergy of pharmacologic, LED light therapy and ultrasonic technologies when prescribed and administered by a trained skin therapist, can lead to a visible improvement in the signs of facial ageing and photodamage, restoring the appearance of healthy, radiant skin. .
文摘目的探讨安罗替尼相关高血压的临床特点。方法检索中国知网、万方、PubMed、Web of Science数据库(截至2023年7月31日),收集安罗替尼相关高血压文献病例报告类文献,提取患者基本情况、安罗替尼用药情况、高血压情况、干预措施和转归等,进行描述性统计分析。结果纳入分析的文献为16篇,患者18例,男性8例,女性10例;年龄27~76岁,平均58岁;非小细胞肺癌13例,结缔组织和软组织恶性肿瘤2例,肝内胆管癌1例,卵巢癌1例,子宫癌1例。联用其他抗肿瘤药物4例;安罗替尼初始剂量均为12 mg/d。发生的高血压分级为1级3例(17%),2级4例(22%),3级9例(50%),4级2例(11%)。除8例患者从服用安罗替尼至发生高血压的时间不详外,其余10例患者从服用安罗替尼至发生高血压的时间在7 d~6个月内,中位时间36(30,42)d,其中7例(39%)发生在服用安罗替尼2个月内。18例患者中出现不同程度乏力6例(33%),头痛6例(33%),头晕5例(28%),呕吐3例(17%),视物模糊2例(11%),恶心1例(6%),抽搐1例(6%)。13例伴其他不良反应,其中手足综合征7例(39%),蛋白尿3例(17%),高脂血症3例(17%),可逆性后部白质脑病综合征2例(11%),癫痫1例(6%),便血1例(6%),皮疹1例(6%)。1~2级患者安罗替尼未调整(6例)或减量治疗(1例)后耐受良好;3~4级患者中,8例停用安罗替尼且接受降压药治疗,2例减量治疗,1例未调整,随访血压控制平稳。结论安罗替尼相关高血压多发生在用药2个月内,往往伴其他不良反应,3级以上高血压常见,但大多数患者经对症处理、停药或减量后转归良好。
基金Yu-Qing Xia Famous Old Chinese Medicine Heritage Workshop of“3+3”Project of Traditional Chinese Medicine Heritage in Beijing,Jing Zhong Yi Ke Zi(2021),No.73National Natural Science Foundation of China,No.81973640+1 种基金Nursery Program of Wangjing Hospital,Chinese Academy of Traditional Chinese Medicine,No.WJYY-YJKT-2022-05China Academy of Traditional Chinese Medicine Wangjing Hospital High-Level Chinese Medicine Hospital Construction Project Chinese Medicine Clinical Evidence-Based Research:The Evidence-Based Research of Electrothermal Acupuncture for Relieving Cancer-Related Fatigue in Patients With Malignant Tumor,No.WYYY-XZKT-2023-20.
文摘BACKGROUND Small cell lung cancer(SCLC)is a common and aggressive subtype of lung cancer.It is characterized by rapid growth and a high mortality rate.Approximately 10%of patients with SCLC present with brain metastases at the time of diagnosis,which is associated with a median survival of 5 mo.This study aimed to summarize the effect of bevacizumab on the progression-free survival(PFS)and overall survival of patients with brain metastasis of SCLC.CASE SUMMARY A 62-year-old man was referred to our hospital in February 2023 because of dizziness and numbness of the right lower extremity without headache or fever for more than four weeks.The patient was diagnosed with limited-stage SCLC.He received 8 cycles of chemotherapy combined with maintenance bevacizumab therapy and achieved a PFS of over 7 mo.CONCLUSION The combination of bevacizumab and irinotecan effectively alleviated brain metastasis in SCLC and prolonged PFS.
文摘目的:基于网络药理学方法筛选固本平喘剂(补骨脂、地龙、防风)中的主要活性成分,探讨其治疗支气管哮喘的作用机制。方法:通过中药系统药理学数据库TCMSP数据库、中药与化学成分数据库,筛选固本平喘剂的活性成分及靶标。利用Genecards、OMIM数据库获得支气管哮喘的潜在靶标基因。将两者靶基因进行映射后通过Cytoscape3.6.1软件构建“成分-靶标”网络、结合String数据库构建蛋白质相互作用网络扩充核心靶点。依托功能注释生物信息学分析平台DAVID数据库对固本平喘剂的作用靶点进行基因本体(gene ontology,GO)生物学过程和基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)通路富集注释分析,通过Autodock vina软件进行分子对接以验证结果。结果:符合筛选条件的共有53个活性成分,补骨脂18个,地龙17个,防风18个,筛选得到固本平喘剂关键成分,包括补骨脂黄酮类、补骨脂查耳酮类、汉黄芩素、补骨脂酚、β-谷甾醇等;通过GenCards、OMIM数据库剔除重复后,共收集支气管哮喘潜在靶点2358个。将固本平喘剂和支气管哮喘靶点进行映射取交集共得到237个交叉靶点,即固本平喘剂治疗支气管哮喘潜在作用靶点。以degree值大于二倍均值的靶点为PTGS2、ESR1、ACHE、ESR2、PTGS1、DPP4、ADORA3,degree值排名前5的靶蛋白为PIK3CA、MAPK3、MAPK1、TP53、AKT1。主要涉及PI3K-Akt信号通路、TNF信号通路、趋化因子信号通路、FoxO信号通路、MAPK信号通路、Toll样受体信号通路、T细胞受体信号通路等。结论:固本平喘剂治疗支气管哮喘潜在作用靶点有PTGS2、ESR1、ACHE、ESR2、PTGS1、DPP4、ADORA3、PIK3CA、MAPK3、MAPK1、TP53、AKT1,可能通过抗感染、调节免疫、抑制气道重塑等发挥作用。
文摘Multiple sclerosis(MS)is an inflammatory demyelinating disease of the central nervous system.The disability caused by inflammatory demyelination clinically dominates the early stages of relapsing-remitting MS and is reversible.Once there is considerable loss of axons,MS patients enter a secondary progressive stage.Disease-modifying drugs currently in use for MS suppress the immune system and reduce relapse rates but are not effective in the progressive stage.Various animal models of MS(mostly mouse and rat)have been established and proved useful in studying the disease process and response to therapy.The experimental autoimmune encephalomyelitis animal studies reviewed here showed that a chronic progressive disease can be induced by immunization with appropriate amounts of myelin oligodendrocyte glycoprotein together with mycobacterium tuberculosis and pertussis toxin in Freund's adjuvant.The clinical manifestations of autoimmune encephalomyelitis disease were prevented or reduced by treatment with certain pharmacological agents given prior to,at,or after peak disease,and the agents had protective effects as shown by inhibiting demyelination and damage to neurons,axons and oligodendrocytes.In the cuprizone-induced toxicity animal studies,the pharmacological agents tested were able to promote remyelination and increase the number of oligodendrocytes when administered therapeutically or prophylactically.A monoclonal IgM antibody protected axons in the spinal cord and preserved motor function in animals inoculated with Theiler's murine encephalomyelitis virus.In all these studies the pharmacological agents were administered singly.A combination therapy may be more effective,especially using agents that target neuroinflammation and neurodegeneration,as they may exert synergistic actions.
文摘Parkinson’s disease (PD) or Paralysis Agitans was first formally described in “An essay on the shaking palsy”, published in 1817 by a British physician named James Parkinson. In the late 1950’s, dopamine was related with the function of the corpus striatum, thus with the control of motor function. But it was not until 1967, when the landmark study of George C. Cotzias, demonstrated that oral L-DOPA, the precursor of dopamine metabolism, was shown to induce remission of PD symptoms, that the definitive association between the two was firmly established. However, later on L-DOPA treatment began to show a loss of effectiveness and demonstrated to induce a variety of undesirable effects, the most prominent being diskinesia. As a result of this, a variety of alternative or complementary pharmacological strategies have been developed. In this chapter we review the wide variety of strategies that have been used through time, which are geared toward reducing the most disabling symptoms of PD. We additionally make some suggestions as to which are the most promising ones.
文摘宫颈神经内分泌癌(neuroendocrine carcinoma of the cervix,NECC)是一种罕见的恶性程度极高的妇科肿瘤。临床上对NECC的组织来源、发病机制并不明确。NECC没有标准的治疗方案,多是结合宫颈鳞状细胞癌、腺癌和小细胞肺癌的治疗经验制定治疗方案。近年来大样本队列基因组研究显示,NECC与宫颈外神经内分泌癌具有不同的基因组学特征,对NECC与宫颈外神经内分泌癌之间的生物学和治疗相关性提出了质疑。由于NECC的罕见性,获得足够数量的患者进行疗效试验的可能性很低,这阻碍了NECC标准治疗方案的制定。基因检测能为NECC靶向药物的个体化治疗提供策略。多项研究结果显示,NECC具有潜在的可调控的治疗靶点,免疫疗法与放射疗法结合可以延长晚期复发性NECC患者的长期生存。综述NECC的分子特征、靶向药物及免疫治疗的研究进展。
文摘他汀类药物是3-羟基-3-甲基戊二酰辅酶A还原酶(3-hydroxy-3-methylglutaryl-coenzyme A reductase,HMGCR)抑制剂,可通过减少胆固醇生物合成和诱导低密度脂蛋白受体表达而降低血浆胆固醇水平,广泛应用于高脂血症的治疗和心脑血管疾病的预防;此外,他汀类药物可能通过阻断细胞周期进展、诱导细胞凋亡、抑制血管生成、抑制肿瘤生长和转移而具有潜在的抗癌作用。卵巢癌预后较差,给患者造成了严重的经济和心理负担。他汀类药物通过抑制甲羟戊酸(mevalonic acid,MVA)途径、促进铁死亡、调节细胞自噬和调节肿瘤微环境(tumor microenvironment,TME)等多种途径发挥抗肿瘤作用和改善卵巢癌化疗耐药现象,同时在某种程度上可抑制卵巢癌细胞增殖,降低卵巢癌患病风险,改善预后,协同并增强化疗药物抗肿瘤作用,降低复发率。综述他汀类药物在卵巢癌的预防和治疗中的研究新进展,以期对未来临床实践提供帮助。