Antioxidants are substances that can prevent or slow damage to cells caused by free radicals, unstable molecules that the body produces as a reaction to environmental and other pressures. Free radicals may play a role...Antioxidants are substances that can prevent or slow damage to cells caused by free radicals, unstable molecules that the body produces as a reaction to environmental and other pressures. Free radicals may play a role in heart disease, cancer and other diseases. If the body cannot process and remove free radicals efficiently, oxidative stress can result. This can harm cells and body function. Free radicals are also known as reactive oxygen species (ROS). In this research, Triptorelin®(TRP) conjugates of triphenylmethanol derivatives (TPMs) were synthesized to evaluate their in vitro lipid peroxidation potency. Comparative lipid peroxidation assays between TRP-TPMs conjugates and the corresponding TPMs derivatives were measured using thiobarbituric reactive substance (TBARS) in a dose- and time-dependent manner following the Fenton’s pathway. Overall, TBARS decreased between 20% - 30% for the treated samples of synthesized conjugates compared to their respective control physical mixtures. These data suggest that TRP-TPMs derivatives can be used to improve the biological activity of TRP.展开更多
Some Triptorelin<sup>®</sup> (TRP) conjugates of triphenylmethanol derivatives (TPMs) with optimized hydrophobicity were synthesized by reacting 2-substituted methoxy benzenes with 1,3,5-trioxane, fol...Some Triptorelin<sup>®</sup> (TRP) conjugates of triphenylmethanol derivatives (TPMs) with optimized hydrophobicity were synthesized by reacting 2-substituted methoxy benzenes with 1,3,5-trioxane, followed by the conjugation with TRP and sebacic acid to produce TRP-TPMs derivatives. Comparative antiproliferative assays between TRP-TPMs conjugates and the corresponding non-covalent physical mixtures of the TPMs derivatives and TRP were used to treat human acute lymphoblastic leukemia (CCRF-CEM), human ovarian adenocarcinoma (SK-OV-3) and mouse preadipocytes (3T3-L1) cells. TRP-TPMs conjugates at the 50 μM inhibited cell proliferation in CCRF-CEM, SK-OV-3 and 3T3-L1 cells by 21% - 37%, 24% - 73%, 37% - 56%, respectively following incubation for 72 h. These findings indicate that TRP-TPMs derivatives have the potential to enhance the biological activity of TRP.展开更多
目的:探究曲普瑞林联合生长激素治疗对女童中枢性性早熟患儿骨代谢的影响。方法:选取2020年8月至2022年5月入院治疗的女童中枢性性早熟108例,按照随机数字表法分为两组,各54例。对照组用曲普瑞林治疗,治疗组在对照组基础上联合生长激素...目的:探究曲普瑞林联合生长激素治疗对女童中枢性性早熟患儿骨代谢的影响。方法:选取2020年8月至2022年5月入院治疗的女童中枢性性早熟108例,按照随机数字表法分为两组,各54例。对照组用曲普瑞林治疗,治疗组在对照组基础上联合生长激素治疗。治疗1年后,比较两组患儿性激素、性腺发育、卵巢功能、生长情况及骨代谢水平。结果:治疗组治疗后卵巢、子宫体积小于对照组,抗苗勒试管激素(anti-Muller hormone,AMH)和抑制素B(inhibin B,INHB)水平低于对照组(P<0.05)。治疗组治疗后预测成年终身高(predictive adult height,PAH)和年平均生长速度(average growth rate,ΔGV)高于对照组,骨龄差值(bone age difference,ΔBV)低于对照组(P<0.05)。治疗组治疗后Ⅰ型前胶原氨基端肽(N-terminal prepeptide of type Ⅰ procollagen,P1NP)和骨钙素N端中分子片段(N-terminal mid-fragment of osteocalcin,N-MID)水平高于对照组(P<0.05),但2组β-胶原降解产物(β-C-terminal telopeptide of type I collagen,β-CTX)的比较,差异无统计学意义(P>0.05)。2组不良反应发生率的比较(18.52%vs.11.11%),差异无统计学意义(P>0.05)。结论:对于女童中枢性性早熟患儿,应用曲普瑞林联合生长激素治疗可有效降低性激素水平,改善卵巢功能和骨代谢水平,从而提高生长速率。展开更多
OBJECTIVE: To study the effects of pretreatment with triptorelin on uterine fibroid before abdominal hysterectomy. METHODS: Fifteen premenopausal Chinese women with symptomatic uterine fibroids requiring hysterectomy ...OBJECTIVE: To study the effects of pretreatment with triptorelin on uterine fibroid before abdominal hysterectomy. METHODS: Fifteen premenopausal Chinese women with symptomatic uterine fibroids requiring hysterectomy were recruited in the study. All patients received monthly intramuscular injections of 3.75 mg triptorelin for three months prior to abdominal hysterectomy. RESULTS: There was significant reduction in the serum levels of oestradiol (68.6%), progesterone (95.6%) and luteinizing hormone (73.9%) and in uterine (45.0%) and fibroid (68.0%) volumes. The serum level of follicle-stimulating hormone and haemoglobin concentration were not significantly different. CONCLUSIONS: Shrinkage of uterine fibroids can be achieved in women who are rendered hypoestrogenic with monthly injections of triptorelin for three months. This treatment modality may be of value prior to hysterectomy or myomectomy especially when the fibroid is large.展开更多
Peptide drugs are known for their high biological safety.However,compared with small molecule drugs,peptide drugs are easily oxidized and hydrolyzed as well as short in half-life.Herein,inspired by the long circulatio...Peptide drugs are known for their high biological safety.However,compared with small molecule drugs,peptide drugs are easily oxidized and hydrolyzed as well as short in half-life.Herein,inspired by the long circulation of albumin in blood,we screened albumin binding peptides(ABPs)from a one-bead one-compound(OBOC)peptide library to increase the half-life of peptide drugs.Beads displaying random peptides were screened using fluorescent labeled human serum albumin.Fluorescent beads with specific binding to albumin were isolated for sequencing.The selected ABPs can effectively bind to albumin,thus possessing the long circulation of albumin.The dissociation constant(K_(D))of ABPs to albumin is up to 1×10^(-8)mol/L.Once one of ABPs(ABP2)was coupled to triptorelin,the circulation half-life of triptorelin in mice was significantly prolonged to 263.50 h much longer than that of triptorelin alone(179.07 h).In addition,the combination therapy using ABP-conjugated triptorelin and doxorubicin(DOX)can effectively inhibit the proliferation of tumor cells in mice.The OBOC screening strategy and resulting ABPs showed great potential for enhancing the delivery efficiency of peptide drugs.展开更多
文摘Antioxidants are substances that can prevent or slow damage to cells caused by free radicals, unstable molecules that the body produces as a reaction to environmental and other pressures. Free radicals may play a role in heart disease, cancer and other diseases. If the body cannot process and remove free radicals efficiently, oxidative stress can result. This can harm cells and body function. Free radicals are also known as reactive oxygen species (ROS). In this research, Triptorelin®(TRP) conjugates of triphenylmethanol derivatives (TPMs) were synthesized to evaluate their in vitro lipid peroxidation potency. Comparative lipid peroxidation assays between TRP-TPMs conjugates and the corresponding TPMs derivatives were measured using thiobarbituric reactive substance (TBARS) in a dose- and time-dependent manner following the Fenton’s pathway. Overall, TBARS decreased between 20% - 30% for the treated samples of synthesized conjugates compared to their respective control physical mixtures. These data suggest that TRP-TPMs derivatives can be used to improve the biological activity of TRP.
文摘Some Triptorelin<sup>®</sup> (TRP) conjugates of triphenylmethanol derivatives (TPMs) with optimized hydrophobicity were synthesized by reacting 2-substituted methoxy benzenes with 1,3,5-trioxane, followed by the conjugation with TRP and sebacic acid to produce TRP-TPMs derivatives. Comparative antiproliferative assays between TRP-TPMs conjugates and the corresponding non-covalent physical mixtures of the TPMs derivatives and TRP were used to treat human acute lymphoblastic leukemia (CCRF-CEM), human ovarian adenocarcinoma (SK-OV-3) and mouse preadipocytes (3T3-L1) cells. TRP-TPMs conjugates at the 50 μM inhibited cell proliferation in CCRF-CEM, SK-OV-3 and 3T3-L1 cells by 21% - 37%, 24% - 73%, 37% - 56%, respectively following incubation for 72 h. These findings indicate that TRP-TPMs derivatives have the potential to enhance the biological activity of TRP.
文摘目的:探究曲普瑞林联合生长激素治疗对女童中枢性性早熟患儿骨代谢的影响。方法:选取2020年8月至2022年5月入院治疗的女童中枢性性早熟108例,按照随机数字表法分为两组,各54例。对照组用曲普瑞林治疗,治疗组在对照组基础上联合生长激素治疗。治疗1年后,比较两组患儿性激素、性腺发育、卵巢功能、生长情况及骨代谢水平。结果:治疗组治疗后卵巢、子宫体积小于对照组,抗苗勒试管激素(anti-Muller hormone,AMH)和抑制素B(inhibin B,INHB)水平低于对照组(P<0.05)。治疗组治疗后预测成年终身高(predictive adult height,PAH)和年平均生长速度(average growth rate,ΔGV)高于对照组,骨龄差值(bone age difference,ΔBV)低于对照组(P<0.05)。治疗组治疗后Ⅰ型前胶原氨基端肽(N-terminal prepeptide of type Ⅰ procollagen,P1NP)和骨钙素N端中分子片段(N-terminal mid-fragment of osteocalcin,N-MID)水平高于对照组(P<0.05),但2组β-胶原降解产物(β-C-terminal telopeptide of type I collagen,β-CTX)的比较,差异无统计学意义(P>0.05)。2组不良反应发生率的比较(18.52%vs.11.11%),差异无统计学意义(P>0.05)。结论:对于女童中枢性性早熟患儿,应用曲普瑞林联合生长激素治疗可有效降低性激素水平,改善卵巢功能和骨代谢水平,从而提高生长速率。
文摘OBJECTIVE: To study the effects of pretreatment with triptorelin on uterine fibroid before abdominal hysterectomy. METHODS: Fifteen premenopausal Chinese women with symptomatic uterine fibroids requiring hysterectomy were recruited in the study. All patients received monthly intramuscular injections of 3.75 mg triptorelin for three months prior to abdominal hysterectomy. RESULTS: There was significant reduction in the serum levels of oestradiol (68.6%), progesterone (95.6%) and luteinizing hormone (73.9%) and in uterine (45.0%) and fibroid (68.0%) volumes. The serum level of follicle-stimulating hormone and haemoglobin concentration were not significantly different. CONCLUSIONS: Shrinkage of uterine fibroids can be achieved in women who are rendered hypoestrogenic with monthly injections of triptorelin for three months. This treatment modality may be of value prior to hysterectomy or myomectomy especially when the fibroid is large.
基金supported by National Natural Science Foundation of China(Nos.51890891,51890894,52073027,and 51773017)National Key R&D Program of China(No.2018YFE0205400)the Fundamental Research Funds for the Central Universities(No.FRFDF-19–001)。
文摘Peptide drugs are known for their high biological safety.However,compared with small molecule drugs,peptide drugs are easily oxidized and hydrolyzed as well as short in half-life.Herein,inspired by the long circulation of albumin in blood,we screened albumin binding peptides(ABPs)from a one-bead one-compound(OBOC)peptide library to increase the half-life of peptide drugs.Beads displaying random peptides were screened using fluorescent labeled human serum albumin.Fluorescent beads with specific binding to albumin were isolated for sequencing.The selected ABPs can effectively bind to albumin,thus possessing the long circulation of albumin.The dissociation constant(K_(D))of ABPs to albumin is up to 1×10^(-8)mol/L.Once one of ABPs(ABP2)was coupled to triptorelin,the circulation half-life of triptorelin in mice was significantly prolonged to 263.50 h much longer than that of triptorelin alone(179.07 h).In addition,the combination therapy using ABP-conjugated triptorelin and doxorubicin(DOX)can effectively inhibit the proliferation of tumor cells in mice.The OBOC screening strategy and resulting ABPs showed great potential for enhancing the delivery efficiency of peptide drugs.
