Background:Nasopharyngeal carcinoma(NPC)exhibits a significant prevalence in the southern regions of China,and paclitaxel(PTX)is frequently employed as a medication for managing advanced NPC.However,drug resistance is...Background:Nasopharyngeal carcinoma(NPC)exhibits a significant prevalence in the southern regions of China,and paclitaxel(PTX)is frequently employed as a medication for managing advanced NPC.However,drug resistance is typically accompanied by a poor prognosis.Exploring the synergistic potential of combining multiple chemotherapeutic agents may represent a promising avenue for optimizing treatment efficacy.Methods:This study investigated whether 3-Methyladenine(3-MA)could potentiated the effect of PTX and its potential molecular mechanism.Samples were divided into the following categories:Negative control(NC)with the solvent dimethyl sulfoxide(DMSO,0.5%v/v),PTX(400 nM),3-MA(4 mM),and PTX(400 nM)+3-MA(4 mM).The viability of NPC cells was assessed using both the cell counting kit-8(CCK-8)assay and the colony formation assay.Microscopic observation was performed to identify morphological cell changes.Flow cytometry was used to assess cell cycle status,mitochondrial membrane potential(MMP),and apoptotic cells.Western blotting was conducted to quantify the protein expression.Results:3-MA enhanced PTX-specific inhibition of NPC cell proliferation.PTX,either alone or in combination with 3-MA,caused cell cycle halt at the G2/M phase in the majority of NPC cells,and the combination treatment of PTX with 3-MA induced a higher rate of NPC cell death compared to PTX alone.Western blotting results revealed the combination of PTX with 3-MA heightened activation of cyclin-dependent kinase 1(CDK1),a key molecule in shifting cells from mitotic arrest to apoptosis,led to a reduction in Myeloid Cell Leukemia 1(MCL-1)expression and an increase in Poly(ADP-ribose)polymerase(PARP)cleavage.Conclusion:The concurrent administration of PTX with 3-MA effectively enhances PTX’s inhibitory impact on NPC and activates the apoptosis signal regulated by CDK1.展开更多
Background:Paclitaxel is a compound derived from Pacific yew bark that induces various cancer cell apoptosis.However,whether it also has anticancer activities in KOSC3 cells,an oral cancer cell line,is unclear.Methods:...Background:Paclitaxel is a compound derived from Pacific yew bark that induces various cancer cell apoptosis.However,whether it also has anticancer activities in KOSC3 cells,an oral cancer cell line,is unclear.Methods:3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide,flow cytometry,and western blotting assays were carried out to assess cell viability,subG1 phase of the cell cycle,and apoptosis-related protein expression,respectively.Results:Ourfindings indicate that paclitaxel could inhibit cell viability and increase the expression of apoptotic markers,including plasma membrane blebbing and the cleavage of poly ADP-ribose polymerase in KOSC3 cells.Also,the treatment with paclitaxel remarkably elevated the percentage of the subG1 phase in KOSC3 cells.In addition,treatment with a pan-caspase inhibitor could recover paclitaxel-inhibited cell viability.Moreover,caspase-8,caspase-9,caspase-7,and BH3 interacting domain death agonist(Bid)were activated in paclitaxel-treated KOSC3 cells.Conclusions:Paclitaxel induced apoptosis through caspase cascade in KOSC3 cells.展开更多
目的·探究“行为干预研究单位孤独症网络家长培训”[the Research Units in Behavioral Intervention(RUBI)Autism Network Parent Training,RUBI-PT]方案的中国本土化改编并对其适应性进行调查。方法·按照文化改编的4个步骤...目的·探究“行为干预研究单位孤独症网络家长培训”[the Research Units in Behavioral Intervention(RUBI)Autism Network Parent Training,RUBI-PT]方案的中国本土化改编并对其适应性进行调查。方法·按照文化改编的4个步骤对RUBI-PT方案进行改编,包括信息收集、初步改编设计、初步改编测试、进一步调整。信息收集阶段邀请了6位儿科专家和2位心理治疗师进行6次焦点小组访谈,并根据专家意见从语言、治疗形式、治疗设置等方面对RUBI-PT方案进行初步改编;初步改编测试阶段招募了16位孤独症谱系障碍(autism spectrum disorder,ASD)患儿的家长,分2批参加线上RUBI-PT,结束后收集项目反馈问卷并行适应性调查分析,最后根据测试结果进行方案的进一步调整。结果·RUBI-PT的初步改编方案由个体培训调整为团体培训,包含8次核心技能课程,采用线上会议形式实施。初步测试结果显示,家长对于上课进度、上课过程、课后作业完成情况、作业点评情况的满意度分别为90%、80%、100%和100%;课程难度方面,第7次课(功能性沟通训练)和第8次课(教授技能)的难度最大。依据上述调查结果和专家小组意见完成进一步调整,最终形成本土化RUBI-PT的改编方案。结论·经过改编和适应性调查,形成了适用于中国ASD儿童家庭的家长行为训练策略即RUBI-PT。展开更多
基金supported by the Science and Technology Innovation Program of Hunan Province(Grant Numbers:2021SK1014 and 2022WZ1027)the Colleges and Universities of Hunan Province(Grant Number:HNJG 20200440)+1 种基金the Scientific Research Fund of Hunan Provincial Education Department(Grant Number:21B0411)the Scientific Research Project of Changsha Central Hospital(Number:YNKY202201).
文摘Background:Nasopharyngeal carcinoma(NPC)exhibits a significant prevalence in the southern regions of China,and paclitaxel(PTX)is frequently employed as a medication for managing advanced NPC.However,drug resistance is typically accompanied by a poor prognosis.Exploring the synergistic potential of combining multiple chemotherapeutic agents may represent a promising avenue for optimizing treatment efficacy.Methods:This study investigated whether 3-Methyladenine(3-MA)could potentiated the effect of PTX and its potential molecular mechanism.Samples were divided into the following categories:Negative control(NC)with the solvent dimethyl sulfoxide(DMSO,0.5%v/v),PTX(400 nM),3-MA(4 mM),and PTX(400 nM)+3-MA(4 mM).The viability of NPC cells was assessed using both the cell counting kit-8(CCK-8)assay and the colony formation assay.Microscopic observation was performed to identify morphological cell changes.Flow cytometry was used to assess cell cycle status,mitochondrial membrane potential(MMP),and apoptotic cells.Western blotting was conducted to quantify the protein expression.Results:3-MA enhanced PTX-specific inhibition of NPC cell proliferation.PTX,either alone or in combination with 3-MA,caused cell cycle halt at the G2/M phase in the majority of NPC cells,and the combination treatment of PTX with 3-MA induced a higher rate of NPC cell death compared to PTX alone.Western blotting results revealed the combination of PTX with 3-MA heightened activation of cyclin-dependent kinase 1(CDK1),a key molecule in shifting cells from mitotic arrest to apoptosis,led to a reduction in Myeloid Cell Leukemia 1(MCL-1)expression and an increase in Poly(ADP-ribose)polymerase(PARP)cleavage.Conclusion:The concurrent administration of PTX with 3-MA effectively enhances PTX’s inhibitory impact on NPC and activates the apoptosis signal regulated by CDK1.
基金The present study was supported by the National Science and Technology Council,Taiwan(MOST-107-2320-B-471-001 to YYL and MOST-110-2320-B-006-025-MY3 to BMH)by An Nan Hospital(ANHRF111-55 to TCC and BMH).
文摘Background:Paclitaxel is a compound derived from Pacific yew bark that induces various cancer cell apoptosis.However,whether it also has anticancer activities in KOSC3 cells,an oral cancer cell line,is unclear.Methods:3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide,flow cytometry,and western blotting assays were carried out to assess cell viability,subG1 phase of the cell cycle,and apoptosis-related protein expression,respectively.Results:Ourfindings indicate that paclitaxel could inhibit cell viability and increase the expression of apoptotic markers,including plasma membrane blebbing and the cleavage of poly ADP-ribose polymerase in KOSC3 cells.Also,the treatment with paclitaxel remarkably elevated the percentage of the subG1 phase in KOSC3 cells.In addition,treatment with a pan-caspase inhibitor could recover paclitaxel-inhibited cell viability.Moreover,caspase-8,caspase-9,caspase-7,and BH3 interacting domain death agonist(Bid)were activated in paclitaxel-treated KOSC3 cells.Conclusions:Paclitaxel induced apoptosis through caspase cascade in KOSC3 cells.
文摘目的·探究“行为干预研究单位孤独症网络家长培训”[the Research Units in Behavioral Intervention(RUBI)Autism Network Parent Training,RUBI-PT]方案的中国本土化改编并对其适应性进行调查。方法·按照文化改编的4个步骤对RUBI-PT方案进行改编,包括信息收集、初步改编设计、初步改编测试、进一步调整。信息收集阶段邀请了6位儿科专家和2位心理治疗师进行6次焦点小组访谈,并根据专家意见从语言、治疗形式、治疗设置等方面对RUBI-PT方案进行初步改编;初步改编测试阶段招募了16位孤独症谱系障碍(autism spectrum disorder,ASD)患儿的家长,分2批参加线上RUBI-PT,结束后收集项目反馈问卷并行适应性调查分析,最后根据测试结果进行方案的进一步调整。结果·RUBI-PT的初步改编方案由个体培训调整为团体培训,包含8次核心技能课程,采用线上会议形式实施。初步测试结果显示,家长对于上课进度、上课过程、课后作业完成情况、作业点评情况的满意度分别为90%、80%、100%和100%;课程难度方面,第7次课(功能性沟通训练)和第8次课(教授技能)的难度最大。依据上述调查结果和专家小组意见完成进一步调整,最终形成本土化RUBI-PT的改编方案。结论·经过改编和适应性调查,形成了适用于中国ASD儿童家庭的家长行为训练策略即RUBI-PT。