In the middle of the 19th century, with a series of excellent novels the great British critical realist writers Charles Dickens created us a vivid world of"hope and despair". Of all his voluminous works, the...In the middle of the 19th century, with a series of excellent novels the great British critical realist writers Charles Dickens created us a vivid world of"hope and despair". Of all his voluminous works, the famous"trilogy of orphans"is all representatives of"hope and de spair. which not only greatly influenced many contemporary writers, but also used for reference by the budding young writers.展开更多
Background/Introduction: Orphans and vulnerable children (OVC) in sub-Saharan Africa have been the focus of much popular and academic writing and the growing body of evidence cannot be overlooked. Existing research fo...Background/Introduction: Orphans and vulnerable children (OVC) in sub-Saharan Africa have been the focus of much popular and academic writing and the growing body of evidence cannot be overlooked. Existing research focuses on projections of OVC numbers, interventions, outcomes and descriptions of care arrangements. A lot of information exists on their poor sexual and reproductive health (SRH) status—most of it quantitative. The purpose of this paper is to present the voice and perceptions of OVC in regards to their SRH. Methods: This was a mixed-methods qualitative study drawing from phenomenology and it used purposive sampling to recruit 129 participants. Results: OVC perceptions and priorities do not always intersect with those of professionals and this has implications for existing and planned interventions. For example some OVC think favorably about early marriages while others have mechanisms of self-protection again SRH harm although this is not usually acknowledged. Conclusions: OVC demonstrate agency;therefore positioning them at the heart of service planning and delivery is an effective strategy in increasing the uptake and impact of interventions seeking to address their sexual and reproductive health needs.展开更多
Orphans and Vulnerable Children (OVC) and their families face many challenges but there are opportunities to provide care and support programmes for them in their communities. This paper presents the achievements and ...Orphans and Vulnerable Children (OVC) and their families face many challenges but there are opportunities to provide care and support programmes for them in their communities. This paper presents the achievements and implications of HIV Programme Development Project (HPDP) funded by World Bank on care and support services for OVC in Osun State, Nigeria. Eight Civil Society Organisations (CSOs) were engaged by Osun State Agency for the Control of AIDS (OSACA) as part of HPDP to provide care and support services for OVC between year 2013 and 2015. Using reporting tools, data collected by the CSOs were entered into District Health Information System 2 (DHIS2) platform and analysed using Microsoft Excel. In addition, Key Informant Interviews (KII) were conducted among the selected CSOs, OVC and the caregivers who were beneficiaries of HPDP in Osun State, Nigeria. A total of 12,353 OVC were reached and about half of them were female. There was an increase in the trends of number of OVC seen and the support services provided from the year 2013 to 2015. Of the 12,353 OVC that benefitted from this programme, 1905 (15.4%) received health care services, 5383 (43.6%) received nutritional services, 5317 (43.0%) received educational services and 9861 (79.8%) were provided with psychosocial support services. About 503 (4.1%) of the OVC received economic strengthening services while 270 (2.2%) of household heads were provided with economic support. However, 3 OVC were lost to follow-up, 14 OVC voluntarily withdrew from the project and 6 OVC died. The FGD and KII revealed that the project was very impactful in transforming the lives of the OVC. Programmes for children orphaned and made vulnerable by HIV/AIDS will contribute to the achievement of HIV/ AIDS prevention and control efforts. The HIV/AIDS free generation can be built by responding to the physical, social and mental needs of these children and their families in their communities. There is a need to scale-up this programme.展开更多
UNICEF, UNAIDS and USAID developed a global strategic framework to guide responses to care and protect orphans and other vulnerable children in the context of HIV/AIDS. In the developing world, about 132 million peopl...UNICEF, UNAIDS and USAID developed a global strategic framework to guide responses to care and protect orphans and other vulnerable children in the context of HIV/AIDS. In the developing world, about 132 million people have lost one or both parents due to the AIDS pandemic and 25 million children have been orphaned by HIV/AIDS in 2010. The HIV prevalence in Cameroon is estimated at 5.1%. As of 2010, there were 304,000 deaths due to AIDS in Cameroon. Out of 1,200,000 orphans and vulnerable children in Cameroon in 2010, 300,000 were AIDS orphans. The HIV/AIDS burden impacts child survival, growth and development in the traditional African setting. With so many orphans in the population, along with many vulnerable children, strategies must be developed to respond more effectively to their critical needs. This study provides a model for OVC care and support in Cameroon. The model was developed out of extensive work using a participatory approach involving traditional, administrative and health stakeholders on OVC in Yaounde I and Yaounde VI Councils, Nanga Eboko Health District, Isangelle, Ekondo Titi, and Bafaka-Balue communities in Cameroon. Consultancy services with PLAN Cameroon, the Pan African Institute for Development-West Africa coupled with facilitation of many training workshops on OVC with Save the orphans Foundation, the Ministry of Social Affairs, and the Ministry of Public Health and working with the National AIDS Control Committee. The essential components of a holistic framework for the care of OVC have been identified. A public health model for the care of OVC and a mechanism for their identification and a referral system for testing OVC for HIV are proposed. Through this model, a mechanism for the effective holistic care of OVC and collaboration is enhanced.展开更多
The purposes of the research aim to： （1） investigate the rehabilitation of the orphans affected by the violence in the Deep South of Thailand; and （2） provide the guideline for the government and institutions to ...The purposes of the research aim to： （1） investigate the rehabilitation of the orphans affected by the violence in the Deep South of Thailand; and （2） provide the guideline for the government and institutions to find ways to rehabilitate the orphans affected by the violence in the Deep South of Thailand. The number of the orphans is drastically increasing because of the violence crisis for a long time since 2004. The government has the policy to rehabilitate the orphans affected by the violence and takes the scholarships for relief their mind related injury Surveillance. The orphans trust the civil society more than the public government. Some opinions suggest the education, the activities, i.e., sports, music to empower the orphans, and the roles of the family and family members are the most important to take care and rehabilitate the orphans by using the religion for conducting ＂the social well-being＂.展开更多
The story goes back to the end of 2007, when Yang Min, Party secretary and deputy chief manager of theNantong Times Clothing Co., Ltd. in Rugao, Jiangsu Province, heard what had happened to an orphan in the city.
On October 12, 2008, a train- ing school for orphans was inaugurated at Nanshanggang Village, Fangshan District,Beijing Municipality. ＂Ours is not an ordinary orphanage,＂ said school official Zhang Mei. ＂It aims to...On October 12, 2008, a train- ing school for orphans was inaugurated at Nanshanggang Village, Fangshan District,Beijing Municipality. ＂Ours is not an ordinary orphanage,＂ said school official Zhang Mei. ＂It aims to produce members of the social elite by letting orphans grow in love and warmth characteristic of wholesome families.＂展开更多
Bettering orphan rescue and assistance policies and improving the upbringing of orphans have been top on the agenda of China＇s civil affairs departments in 2006. A survey conducted by the Ministry of Civil Affairs in...Bettering orphan rescue and assistance policies and improving the upbringing of orphans have been top on the agenda of China＇s civil affairs departments in 2006. A survey conducted by the Ministry of Civil Affairs in 2005 shows that one-third of the country＇s 573,＇30 orphans do not receive regular, system-guaranteed help. Some orphans have been forced to drop out of school and lead a vagrant life, Some have even become petty thieves.展开更多
Nuclear receptor subfamily 2 group F member 1(NR2F1,also called COUP-TF1)is a transcription factor and part of the steroid/thyroid hormone receptor superfamily(Gay et al.,2002).NR2F1 is an orphan receptor that dimeriz...Nuclear receptor subfamily 2 group F member 1(NR2F1,also called COUP-TF1)is a transcription factor and part of the steroid/thyroid hormone receptor superfamily(Gay et al.,2002).NR2F1 is an orphan receptor that dimerizes to bind DNA and acts as a repressor as well as an activator of the target genes(Gay et al.,2002;Bertacchi et al.,2019;Bonzano et al.,2023).展开更多
G protein-coupled receptor 37(GPR37)is an orphan receptor predominantly expressed in the brain,particularly in oligodendrocytes and certain types of neurons.Notably,it has been shown that the N-terminal domain of GPR3...G protein-coupled receptor 37(GPR37)is an orphan receptor predominantly expressed in the brain,particularly in oligodendrocytes and certain types of neurons.Notably,it has been shown that the N-terminal domain of GPR37 undergoes proteolysis under normal physiological conditions,resulting in the formation of cleaved receptor forms and the release of its ectodomain(ecto-GPR37)into the extracellular milieu(Mattila et al.,2021).Importantly,ecto-GPR37 density is increased in cerebrospinal fluid(CSF)of patients suffering from sporadic Parkinson’s disease(PD),together with an abnormal GPR37 processing in post-mortem PD substantia nigra(Moratóet al.,2021;Figure 1A).展开更多
The government has recently stepped up assistance to the most vulnerable children On January 13, Zhang Xinyu, a resident in Banan District, southwest China’s Chongqing Municipality,
Chinese Premier Wen Jiabao visits AIDS orphans in Shangcai County,central China’s Henan Province,on November 30,a day before the 20th World AIDS Day. The region of Shangcai has the highest concentration of people liv...Chinese Premier Wen Jiabao visits AIDS orphans in Shangcai County,central China’s Henan Province,on November 30,a day before the 20th World AIDS Day. The region of Shangcai has the highest concentration of people living with HIV/AIDS in China. The Chinese Government has released a package of policies that offer people living with HIV/AIDS free medicine,health checks and consultations,as well as free schooling to AIDS orphans.展开更多
Since Shanghai opened to the outside, a large number of foreign wives have lived there. They have organized a charitable association which has attracted people’s attention. They donate money and material goods to the...Since Shanghai opened to the outside, a large number of foreign wives have lived there. They have organized a charitable association which has attracted people’s attention. They donate money and material goods to the Shanghai Children’s Welfare House, as well as contributing their maternal love to the Chinese orphans. Every week, no matter whether it is raining or windy, they visit, holding the children in their arms and feeding them. Some of展开更多
IT was already New Year’s Eve, so could not postpone paying my debt any longer. In the morning two of my colleagues in the public relations department and I made the long journey to the Beijing Children’s Welfare Ho...IT was already New Year’s Eve, so could not postpone paying my debt any longer. In the morning two of my colleagues in the public relations department and I made the long journey to the Beijing Children’s Welfare Home to fulfill my annual charitable contribution. Later that afternoon we hurried to Xiaoguan to visit our department secretary who had just given birth to a son. These two visits on the same展开更多
Neuron-derived clone 77 (Nur77) is a member of the NR4A subfamily that plays critical roles in apoptosis, survival, proliferation, autophagy, angiogenesis, inflammatory responses, DNA repair, glycolipid metabolism and...Neuron-derived clone 77 (Nur77) is a member of the NR4A subfamily that plays critical roles in apoptosis, survival, proliferation, autophagy, angiogenesis, inflammatory responses, DNA repair, glycolipid metabolism and energy consumption. The deregulation of Nur77 signalling often relates to various serious diseases, including cancer and non-cancer diseases. A systematic review is necessary for the better understanding of Nur77 in clinical treatment. In this article, we comprehensively conclude the lipid regulation function and expression of Nur77, and its role in COPD. Finally, we prospect that development of drugs and clinical biochemical investigations targeting of Nur77 has considerable potential within healthcare.展开更多
Objective To evaluate the clinical value of siltuximab in the treatment of Castleman disease based on multicriteria decision analysis(MCDA)and evidence and value:Impact on decision making(EVIDEM)framework.Methods The ...Objective To evaluate the clinical value of siltuximab in the treatment of Castleman disease based on multicriteria decision analysis(MCDA)and evidence and value:Impact on decision making(EVIDEM)framework.Methods The evidence matrix for quantitative analysis of MCDA was extracted through literature research,and the weight of each evaluation index was calculated by the maximum differentiation measure in conjoint analysis.Besides,the clinical value of siltuximab in the treatment of Castleman disease was analyzed quantitatively and qualitatively based on the results of expert questionnaire surveys.Results and Conclusion The clinical value score of siltuximab was 0.491,and the weight ratio of“therapeutic benefit”(15.39%),“drug effectiveness”(14.46%)and“drug safety”(11.43%)were the three largest.Among the indexes of“drug effectiveness”“drug safety”“patient reported outcome”“therapeutic benefit”and“non-medical cost”,siltuximab for Castleman disease was considered to be a more valuable treatment option than other first-line therapies.By qualitative analysis,57%experts believed that siltuximab was a better treatment option.The indexes that contribute the most to the overall clinical value of siltuximab are“therapeutic benefit”“drug effectiveness”and“quality of evidence”,while the indexes that have a negative impact on the clinical value of siltuximab is“drug treatment cost”.展开更多
Objectives:Gastric cancer(GC)is often associated with high invasiveness,epithelial-mesenchymal transition(EMT),and resistance to 5-fluorouracil(5-FU),highlighting the need for novel therapeutic targets.This study expl...Objectives:Gastric cancer(GC)is often associated with high invasiveness,epithelial-mesenchymal transition(EMT),and resistance to 5-fluorouracil(5-FU),highlighting the need for novel therapeutic targets.This study explored whether diallyl disulfide(DADS)upregulates retinoic acid-related orphan receptor alpha(RORα)to weaken the protein kinase C alpha(PKCα)/RORα-mediated RORα/β-catenin pathway,thereby inhibiting GC cell invasion,epithelial-mesenchymal transition(EMT),and enhancing 5-FU sensitivity.Methods:Human GC cell lines MGC-803 and SGC7901 were treated with DADS,RORαagonist SR1078/antagonist T0901317,and PKCαagonist TPA/antagonist GO6976.Cell proliferation(MTT),migration(scratch assay),invasion(Transwell),protein expression(Western blot),protein interactions(coimmunoprecipitation),and localization(immunofluorescence)were detected.Apoptosis and 5-FU sensitivity-related proteins were examined.Experiments were triplicated;statistics used t-test/ANOVA(p<0.05).Results:DADS/SR1078 inhibited GC cell proliferation/migration/invasion,upregulated RORα/E-cadherin,downregulated nuclearβ-catenin/TGF-β1/Rac1/Vimentin,and weakened EMT(reversed by T0901317).DADS/TPA upregulated RORα/p-RORα/PKCα/p-PKCα,promoted PKCα-RORαbinding,and downregulated RORα/β-catenin target genes(counteracted by GO6976).DADS upregulated caspase-3 and downregulated Bcl-2/P-gp/XIAP via RORα,promoting apoptosis and 5-FU sensitivity.Conclusion:DADS inhibits GC progression and enhances 5-FU sensitivity by PKCα/RORα-mediated downregulation of RORα/β-catenin signaling,paralleling SR1078/TPA effects.It may act as a novel RORαagonist for GC therapy.展开更多
文摘In the middle of the 19th century, with a series of excellent novels the great British critical realist writers Charles Dickens created us a vivid world of"hope and despair". Of all his voluminous works, the famous"trilogy of orphans"is all representatives of"hope and de spair. which not only greatly influenced many contemporary writers, but also used for reference by the budding young writers.
文摘Background/Introduction: Orphans and vulnerable children (OVC) in sub-Saharan Africa have been the focus of much popular and academic writing and the growing body of evidence cannot be overlooked. Existing research focuses on projections of OVC numbers, interventions, outcomes and descriptions of care arrangements. A lot of information exists on their poor sexual and reproductive health (SRH) status—most of it quantitative. The purpose of this paper is to present the voice and perceptions of OVC in regards to their SRH. Methods: This was a mixed-methods qualitative study drawing from phenomenology and it used purposive sampling to recruit 129 participants. Results: OVC perceptions and priorities do not always intersect with those of professionals and this has implications for existing and planned interventions. For example some OVC think favorably about early marriages while others have mechanisms of self-protection again SRH harm although this is not usually acknowledged. Conclusions: OVC demonstrate agency;therefore positioning them at the heart of service planning and delivery is an effective strategy in increasing the uptake and impact of interventions seeking to address their sexual and reproductive health needs.
文摘Orphans and Vulnerable Children (OVC) and their families face many challenges but there are opportunities to provide care and support programmes for them in their communities. This paper presents the achievements and implications of HIV Programme Development Project (HPDP) funded by World Bank on care and support services for OVC in Osun State, Nigeria. Eight Civil Society Organisations (CSOs) were engaged by Osun State Agency for the Control of AIDS (OSACA) as part of HPDP to provide care and support services for OVC between year 2013 and 2015. Using reporting tools, data collected by the CSOs were entered into District Health Information System 2 (DHIS2) platform and analysed using Microsoft Excel. In addition, Key Informant Interviews (KII) were conducted among the selected CSOs, OVC and the caregivers who were beneficiaries of HPDP in Osun State, Nigeria. A total of 12,353 OVC were reached and about half of them were female. There was an increase in the trends of number of OVC seen and the support services provided from the year 2013 to 2015. Of the 12,353 OVC that benefitted from this programme, 1905 (15.4%) received health care services, 5383 (43.6%) received nutritional services, 5317 (43.0%) received educational services and 9861 (79.8%) were provided with psychosocial support services. About 503 (4.1%) of the OVC received economic strengthening services while 270 (2.2%) of household heads were provided with economic support. However, 3 OVC were lost to follow-up, 14 OVC voluntarily withdrew from the project and 6 OVC died. The FGD and KII revealed that the project was very impactful in transforming the lives of the OVC. Programmes for children orphaned and made vulnerable by HIV/AIDS will contribute to the achievement of HIV/ AIDS prevention and control efforts. The HIV/AIDS free generation can be built by responding to the physical, social and mental needs of these children and their families in their communities. There is a need to scale-up this programme.
文摘UNICEF, UNAIDS and USAID developed a global strategic framework to guide responses to care and protect orphans and other vulnerable children in the context of HIV/AIDS. In the developing world, about 132 million people have lost one or both parents due to the AIDS pandemic and 25 million children have been orphaned by HIV/AIDS in 2010. The HIV prevalence in Cameroon is estimated at 5.1%. As of 2010, there were 304,000 deaths due to AIDS in Cameroon. Out of 1,200,000 orphans and vulnerable children in Cameroon in 2010, 300,000 were AIDS orphans. The HIV/AIDS burden impacts child survival, growth and development in the traditional African setting. With so many orphans in the population, along with many vulnerable children, strategies must be developed to respond more effectively to their critical needs. This study provides a model for OVC care and support in Cameroon. The model was developed out of extensive work using a participatory approach involving traditional, administrative and health stakeholders on OVC in Yaounde I and Yaounde VI Councils, Nanga Eboko Health District, Isangelle, Ekondo Titi, and Bafaka-Balue communities in Cameroon. Consultancy services with PLAN Cameroon, the Pan African Institute for Development-West Africa coupled with facilitation of many training workshops on OVC with Save the orphans Foundation, the Ministry of Social Affairs, and the Ministry of Public Health and working with the National AIDS Control Committee. The essential components of a holistic framework for the care of OVC have been identified. A public health model for the care of OVC and a mechanism for their identification and a referral system for testing OVC for HIV are proposed. Through this model, a mechanism for the effective holistic care of OVC and collaboration is enhanced.
文摘The purposes of the research aim to： （1） investigate the rehabilitation of the orphans affected by the violence in the Deep South of Thailand; and （2） provide the guideline for the government and institutions to find ways to rehabilitate the orphans affected by the violence in the Deep South of Thailand. The number of the orphans is drastically increasing because of the violence crisis for a long time since 2004. The government has the policy to rehabilitate the orphans affected by the violence and takes the scholarships for relief their mind related injury Surveillance. The orphans trust the civil society more than the public government. Some opinions suggest the education, the activities, i.e., sports, music to empower the orphans, and the roles of the family and family members are the most important to take care and rehabilitate the orphans by using the religion for conducting ＂the social well-being＂.
文摘The story goes back to the end of 2007, when Yang Min, Party secretary and deputy chief manager of theNantong Times Clothing Co., Ltd. in Rugao, Jiangsu Province, heard what had happened to an orphan in the city.
文摘On October 12, 2008, a train- ing school for orphans was inaugurated at Nanshanggang Village, Fangshan District,Beijing Municipality. ＂Ours is not an ordinary orphanage,＂ said school official Zhang Mei. ＂It aims to produce members of the social elite by letting orphans grow in love and warmth characteristic of wholesome families.＂
文摘Bettering orphan rescue and assistance policies and improving the upbringing of orphans have been top on the agenda of China＇s civil affairs departments in 2006. A survey conducted by the Ministry of Civil Affairs in 2005 shows that one-third of the country＇s 573,＇30 orphans do not receive regular, system-guaranteed help. Some orphans have been forced to drop out of school and lead a vagrant life, Some have even become petty thieves.
文摘Nuclear receptor subfamily 2 group F member 1(NR2F1,also called COUP-TF1)is a transcription factor and part of the steroid/thyroid hormone receptor superfamily(Gay et al.,2002).NR2F1 is an orphan receptor that dimerizes to bind DNA and acts as a repressor as well as an activator of the target genes(Gay et al.,2002;Bertacchi et al.,2019;Bonzano et al.,2023).
基金FEDER/Ministerio de Ciencia,Innovacióny Universidades-Agencia Estatal de Investigación(PID2023-147425OB-I00 to FC)Agència de Gestiód’Ajuts Universitaris i de Recerca(AGAUR)-Generalitat de Catalunya(2021 SGR 00698 to FC).
文摘G protein-coupled receptor 37(GPR37)is an orphan receptor predominantly expressed in the brain,particularly in oligodendrocytes and certain types of neurons.Notably,it has been shown that the N-terminal domain of GPR37 undergoes proteolysis under normal physiological conditions,resulting in the formation of cleaved receptor forms and the release of its ectodomain(ecto-GPR37)into the extracellular milieu(Mattila et al.,2021).Importantly,ecto-GPR37 density is increased in cerebrospinal fluid(CSF)of patients suffering from sporadic Parkinson’s disease(PD),together with an abnormal GPR37 processing in post-mortem PD substantia nigra(Moratóet al.,2021;Figure 1A).
文摘The government has recently stepped up assistance to the most vulnerable children On January 13, Zhang Xinyu, a resident in Banan District, southwest China’s Chongqing Municipality,
文摘Chinese Premier Wen Jiabao visits AIDS orphans in Shangcai County,central China’s Henan Province,on November 30,a day before the 20th World AIDS Day. The region of Shangcai has the highest concentration of people living with HIV/AIDS in China. The Chinese Government has released a package of policies that offer people living with HIV/AIDS free medicine,health checks and consultations,as well as free schooling to AIDS orphans.
文摘Since Shanghai opened to the outside, a large number of foreign wives have lived there. They have organized a charitable association which has attracted people’s attention. They donate money and material goods to the Shanghai Children’s Welfare House, as well as contributing their maternal love to the Chinese orphans. Every week, no matter whether it is raining or windy, they visit, holding the children in their arms and feeding them. Some of
文摘IT was already New Year’s Eve, so could not postpone paying my debt any longer. In the morning two of my colleagues in the public relations department and I made the long journey to the Beijing Children’s Welfare Home to fulfill my annual charitable contribution. Later that afternoon we hurried to Xiaoguan to visit our department secretary who had just given birth to a son. These two visits on the same
文摘Neuron-derived clone 77 (Nur77) is a member of the NR4A subfamily that plays critical roles in apoptosis, survival, proliferation, autophagy, angiogenesis, inflammatory responses, DNA repair, glycolipid metabolism and energy consumption. The deregulation of Nur77 signalling often relates to various serious diseases, including cancer and non-cancer diseases. A systematic review is necessary for the better understanding of Nur77 in clinical treatment. In this article, we comprehensively conclude the lipid regulation function and expression of Nur77, and its role in COPD. Finally, we prospect that development of drugs and clinical biochemical investigations targeting of Nur77 has considerable potential within healthcare.
文摘Objective To evaluate the clinical value of siltuximab in the treatment of Castleman disease based on multicriteria decision analysis(MCDA)and evidence and value:Impact on decision making(EVIDEM)framework.Methods The evidence matrix for quantitative analysis of MCDA was extracted through literature research,and the weight of each evaluation index was calculated by the maximum differentiation measure in conjoint analysis.Besides,the clinical value of siltuximab in the treatment of Castleman disease was analyzed quantitatively and qualitatively based on the results of expert questionnaire surveys.Results and Conclusion The clinical value score of siltuximab was 0.491,and the weight ratio of“therapeutic benefit”(15.39%),“drug effectiveness”(14.46%)and“drug safety”(11.43%)were the three largest.Among the indexes of“drug effectiveness”“drug safety”“patient reported outcome”“therapeutic benefit”and“non-medical cost”,siltuximab for Castleman disease was considered to be a more valuable treatment option than other first-line therapies.By qualitative analysis,57%experts believed that siltuximab was a better treatment option.The indexes that contribute the most to the overall clinical value of siltuximab are“therapeutic benefit”“drug effectiveness”and“quality of evidence”,while the indexes that have a negative impact on the clinical value of siltuximab is“drug treatment cost”.
基金supported by The National Natural Scientific Foundation of China(No.81973532,No.81374013)The Natural Science Foundation of Hunan Province of China(No.2020JJ4522,No.2020JJ4529)+4 种基金The Patency Foundation of Innovation Platform of Hunan Provincial University of China(No.17K081)The Scientific Research Foundation ofHealth and Family Planning Committee of Hunan Province of China(No.A2015-2,No.B2015-182)The Scientific Research Foundation of Hunan Province Education Department of China(No.19C1610)Science and Technology Project of Jiangxi Provincial Administration of Traditional Chinese Medicine(No.2021B715)The Scientific Research Foundation of University of South China(No.220XNK002).
文摘Objectives:Gastric cancer(GC)is often associated with high invasiveness,epithelial-mesenchymal transition(EMT),and resistance to 5-fluorouracil(5-FU),highlighting the need for novel therapeutic targets.This study explored whether diallyl disulfide(DADS)upregulates retinoic acid-related orphan receptor alpha(RORα)to weaken the protein kinase C alpha(PKCα)/RORα-mediated RORα/β-catenin pathway,thereby inhibiting GC cell invasion,epithelial-mesenchymal transition(EMT),and enhancing 5-FU sensitivity.Methods:Human GC cell lines MGC-803 and SGC7901 were treated with DADS,RORαagonist SR1078/antagonist T0901317,and PKCαagonist TPA/antagonist GO6976.Cell proliferation(MTT),migration(scratch assay),invasion(Transwell),protein expression(Western blot),protein interactions(coimmunoprecipitation),and localization(immunofluorescence)were detected.Apoptosis and 5-FU sensitivity-related proteins were examined.Experiments were triplicated;statistics used t-test/ANOVA(p<0.05).Results:DADS/SR1078 inhibited GC cell proliferation/migration/invasion,upregulated RORα/E-cadherin,downregulated nuclearβ-catenin/TGF-β1/Rac1/Vimentin,and weakened EMT(reversed by T0901317).DADS/TPA upregulated RORα/p-RORα/PKCα/p-PKCα,promoted PKCα-RORαbinding,and downregulated RORα/β-catenin target genes(counteracted by GO6976).DADS upregulated caspase-3 and downregulated Bcl-2/P-gp/XIAP via RORα,promoting apoptosis and 5-FU sensitivity.Conclusion:DADS inhibits GC progression and enhances 5-FU sensitivity by PKCα/RORα-mediated downregulation of RORα/β-catenin signaling,paralleling SR1078/TPA effects.It may act as a novel RORαagonist for GC therapy.
