Rheumatoid arthritis(RA)is a chronic inflammatory and destructive arthropathy with a high deformity rate.Despite numerous studies and clinical trials,no curative treatment is available for large weight-bearing joints....Rheumatoid arthritis(RA)is a chronic inflammatory and destructive arthropathy with a high deformity rate.Despite numerous studies and clinical trials,no curative treatment is available for large weight-bearing joints.Intra-articular(IA)injections could deliver high concentrations of drug to the afflicted joint and improve the drug efficacy while reducing systemic toxicity.However,free drugs are rapidly cleared from synovial fluid and do not significantly halt the progression of joint disease.Herein,a phospholipids-based controlledrelease gel was prepared for sustained IA delivery of celastrol(CEL)and the therapeutic efficiencywas evaluated in a rheumatoid arthritis rabbitmodel.The CEL-loaded gel(CEL-gel)contained up to 70%phospholipids yetwas easy to inject.After injecting into the joint cavity,CEL-gel achieved sol to gel phase transition without special stimuli and gelling agent.In vitro release and in vivo pharmacokinetic studies evidenced the stable and sustained release action of CEL-gel.A single IA injection of CEL-gel could maintain therapeutic efficiency for about 25 d and showed much better anti-arthritic efficacy compared to repeated injections of free drug solution(CEL-sol).Furthermore,the IA injection of CEL-gel greatly reduced the systemic toxicity of CEL.With good biocompatibility and biodegradability,CEL-gel might be a promising IA drug delivery system.展开更多
Objective:Research on the biological mechanisms by which the liver controls dispersion and regulates emotion usually focuses on psychological stress.This study investigated the biological mechanisms underlying the liv...Objective:Research on the biological mechanisms by which the liver controls dispersion and regulates emotion usually focuses on psychological stress.This study investigated the biological mechanisms underlying the liver's regulation of emotion using the Trier Social Stress Test (TSST).Differences in subjective stress,subjective emotion,and physiological responses were examined between healthy women (Group A) and depressed women with liver qi stagnation syndrome (Group B).Method:Subjects were 72 women who met the inclusion criteria after physical examination.The EPQ-RSC,BAI,and BDI-21 were used to assess personality and emotion.Subjects completed a 5-point scale to measure subjective stress.Heart rate and heart rate variability were measured.To measure changes in activity of the locus coeruleus-norepinephrine (LCNE)/autonomic nervous system and the HPA axis,saliva samples were collected at the end of the rest and preparation periods,and 5 time pionts after the TSST task.The PAD Emotion Scale was completed at 4 time points before and after the TSST task.Saliva cortisol was tested.These indexes were compared between the two groups.Results:There were 33 subjects in Group A and 39 subjects in Group B.Subjects in Group B had lower levels of stress,pleasure,and dominance,but higher arousal (after the task:P <.05).They also had higher saliva cortisol levels,slower heart rate,higher BVP,and more stable RMSSD and SDNN.Conclusion:In relation to mood,the liver's regulation of emotion mainly affects negative emotional experience and the sense of control Regarding the biological mechanisms underlying the liver's regulation of emotion,the activity of the LC-NE/autonomic nervous system in women is more obvious in response to psychological stress when the dispersion of the liver is normal.The activity of the HPA axis in women is more obvious in response to psychological stress when the dispersion of the liver is abnormal.展开更多
Acute liver injury(ALI)has an elevated fatality rate due to untimely and ineffective treatment.Although,schisandrin B(SchB)has been extensively used to treat diverse liver diseases,its therapeutic efficacy on ALI was ...Acute liver injury(ALI)has an elevated fatality rate due to untimely and ineffective treatment.Although,schisandrin B(SchB)has been extensively used to treat diverse liver diseases,its therapeutic efficacy on ALI was limited due to its high hydrophobicity.Palmitic acid-modified serum albumin(PSA)is not only an effective carrier for hydrophobic drugs,but also has a superb targeting effect via scavenger receptor-A(SR-A)on the M1 macrophages,which are potential therapeutic targets for ALI.Compared with the common macrophage-targeted delivery systems,PSA enables site-specific drug delivery to reduce off-target toxicity.Herein,we prepared SchB-PSA nanoparticles and further assessed their therapeutic effect on ALI.In vitro,compared with human serum albumin encapsulated SchB nanoparticles(SchB-HSA NPs),the SchB-PSA NPs exhibited more potent cytotoxicity on lipopolysaccharide(LPS)stimulated Raw264.7(LAR)cells,and LAR cells took up PSA NPs 8.79 times more than HSA NPs.As expected,the PSA NPs also accumulated more in the liver.Moreover,SchB-PSA NPs dramatically reduced the activation of NF-κB signaling,and significantly relieved inflammatory response and hepatic necrosis.Notably,the high dose of SchB-PSA NPs improved the survival rate in 72 h of ALI mice to 75%.Hence,SchB-PSA NPs are promising to treat ALI.展开更多
Objective:To investigate the diversity of experiences of sadness emotion and physiological responses among female college students with high neuroticism (HN) and low neuroticism (LN) during the late luteal phase (LLP)...Objective:To investigate the diversity of experiences of sadness emotion and physiological responses among female college students with high neuroticism (HN) and low neuroticism (LN) during the late luteal phase (LLP) and early follicular phase (EFP).Methods:Forty-two participants were classified as the HN group and 41 as the LN group based on their neuroticism score (Eysenck Personality Questionnaire Short Scale for Chinese).Participants watched sadness-inducing experimental films during the LLP and EFP.Results:The HN group showed similar sadness intensities in both phases.The LN group showed higher sadness intensity in the LLP than the EFP.The LN group's sadness scale assessments were lower than the HN group in both phases.The blood volume pulse in the HN group fell in both the LLP and EFP (both P <.001).The root mean square standard deviation of NN intervals rose in the EFP in the HN group before and after watching experimental films (P =.027),but fell in the LN group (P >.05).Between-group comparisons showed heart rate was significantly lower in the HN group than the LN group during EFP (P =.009),but there were no statistically significant differences in subjective experience and physiological data during LLP.The HN group had stronger sadness feelings and greater sadness arousal than the LN group during EFP.There were significant associations between menstrual cycle-related changes in sadness ratings and changes in physiological outcomes.Conclusion:Women with HN have less fluctuation in sadness than those with LN during the menstrual cycle,but experience strong sadness feelings in the LLP.Women with HN show stronger physiological responses in the EFP than those with LN,and have the highest responses in the LLP.展开更多
Breast cancer and metastasis remain great challenges in clinical therapy.Compared with monotherapy,combination therapy,especially mediated by nanomedicine delivery strategy,significantly improves the therapeutic effic...Breast cancer and metastasis remain great challenges in clinical therapy.Compared with monotherapy,combination therapy,especially mediated by nanomedicine delivery strategy,significantly improves the therapeutic efficacy and reduces undesired toxicity.Cyclooxygenase-2(COX-2)inhibitors are widely used for adjuvant chemotherapy because COX-2 is overexpressed in virtually all cancer cell lines to regulate tumor progression by catalyzing prostaglandin E2(PGE2)synthesis.This drug combination strategy is still required to be improved due to some unsatisfactory clinical trial results.Intricate processes of tumor growth and metastasis are orchestrated by multiple proteins in addition to COX-2,which are modified and transported by Golgi apparatus.Hence,disrupting the structure and function of Golgi apparatus can inhibit the secretion of tumor-related proteins and further suppress carcinoma progression and metastasis.Since COX-2 is also enriched within Golgi apparatus in tumor cells,COX-2 inhibitors and Golgi disrupting agents can be co-delivered to Golgi apparatus to maximize the synergy.In this work,we developed a human serum albumin(HSA)nanoparticle encapsulating pirarubicin(THP),retinoic acid(RA),and indomethacin(IMC),called TIR-HSA,which was observed to be localized in Golgi complex of 4T1 cells.Owing to the synergistic effect of these three drugs,TIR-HSA inhibited the proliferation,migration,and invasion of tumor cells,enhanced the apoptotic rate,and improved the immunosuppressive tumor microenvironment,which remarkably regressed the tumor growth and metastasis and prolonged the survival period of 4T1-bearing mice.展开更多
基金financially supported by the National Natural Science Foundation of China (Nos. 82173758, China)Sichuan major science and technology project on biotechnology and medicine (2018SZDZX0018, China)
文摘Rheumatoid arthritis(RA)is a chronic inflammatory and destructive arthropathy with a high deformity rate.Despite numerous studies and clinical trials,no curative treatment is available for large weight-bearing joints.Intra-articular(IA)injections could deliver high concentrations of drug to the afflicted joint and improve the drug efficacy while reducing systemic toxicity.However,free drugs are rapidly cleared from synovial fluid and do not significantly halt the progression of joint disease.Herein,a phospholipids-based controlledrelease gel was prepared for sustained IA delivery of celastrol(CEL)and the therapeutic efficiencywas evaluated in a rheumatoid arthritis rabbitmodel.The CEL-loaded gel(CEL-gel)contained up to 70%phospholipids yetwas easy to inject.After injecting into the joint cavity,CEL-gel achieved sol to gel phase transition without special stimuli and gelling agent.In vitro release and in vivo pharmacokinetic studies evidenced the stable and sustained release action of CEL-gel.A single IA injection of CEL-gel could maintain therapeutic efficiency for about 25 d and showed much better anti-arthritic efficacy compared to repeated injections of free drug solution(CEL-sol).Furthermore,the IA injection of CEL-gel greatly reduced the systemic toxicity of CEL.With good biocompatibility and biodegradability,CEL-gel might be a promising IA drug delivery system.
基金This study was supported by the National Science Foundation of China(No.81373771)the National Basic Research Program of China(No.2011CB505101).
文摘Objective:Research on the biological mechanisms by which the liver controls dispersion and regulates emotion usually focuses on psychological stress.This study investigated the biological mechanisms underlying the liver's regulation of emotion using the Trier Social Stress Test (TSST).Differences in subjective stress,subjective emotion,and physiological responses were examined between healthy women (Group A) and depressed women with liver qi stagnation syndrome (Group B).Method:Subjects were 72 women who met the inclusion criteria after physical examination.The EPQ-RSC,BAI,and BDI-21 were used to assess personality and emotion.Subjects completed a 5-point scale to measure subjective stress.Heart rate and heart rate variability were measured.To measure changes in activity of the locus coeruleus-norepinephrine (LCNE)/autonomic nervous system and the HPA axis,saliva samples were collected at the end of the rest and preparation periods,and 5 time pionts after the TSST task.The PAD Emotion Scale was completed at 4 time points before and after the TSST task.Saliva cortisol was tested.These indexes were compared between the two groups.Results:There were 33 subjects in Group A and 39 subjects in Group B.Subjects in Group B had lower levels of stress,pleasure,and dominance,but higher arousal (after the task:P <.05).They also had higher saliva cortisol levels,slower heart rate,higher BVP,and more stable RMSSD and SDNN.Conclusion:In relation to mood,the liver's regulation of emotion mainly affects negative emotional experience and the sense of control Regarding the biological mechanisms underlying the liver's regulation of emotion,the activity of the LC-NE/autonomic nervous system in women is more obvious in response to psychological stress when the dispersion of the liver is normal.The activity of the HPA axis in women is more obvious in response to psychological stress when the dispersion of the liver is abnormal.
基金This project is financially supported by grants from the National Natural Science Foundation of China(82173758 and 81872804)Sichuan major science and technology project on biotechnology and medicine(2018SZDZX0018).
文摘Acute liver injury(ALI)has an elevated fatality rate due to untimely and ineffective treatment.Although,schisandrin B(SchB)has been extensively used to treat diverse liver diseases,its therapeutic efficacy on ALI was limited due to its high hydrophobicity.Palmitic acid-modified serum albumin(PSA)is not only an effective carrier for hydrophobic drugs,but also has a superb targeting effect via scavenger receptor-A(SR-A)on the M1 macrophages,which are potential therapeutic targets for ALI.Compared with the common macrophage-targeted delivery systems,PSA enables site-specific drug delivery to reduce off-target toxicity.Herein,we prepared SchB-PSA nanoparticles and further assessed their therapeutic effect on ALI.In vitro,compared with human serum albumin encapsulated SchB nanoparticles(SchB-HSA NPs),the SchB-PSA NPs exhibited more potent cytotoxicity on lipopolysaccharide(LPS)stimulated Raw264.7(LAR)cells,and LAR cells took up PSA NPs 8.79 times more than HSA NPs.As expected,the PSA NPs also accumulated more in the liver.Moreover,SchB-PSA NPs dramatically reduced the activation of NF-κB signaling,and significantly relieved inflammatory response and hepatic necrosis.Notably,the high dose of SchB-PSA NPs improved the survival rate in 72 h of ALI mice to 75%.Hence,SchB-PSA NPs are promising to treat ALI.
基金This study was supported by the National Natural Science Foundation of China(81373771)the National Key Basic Research Development Program(973 Program:2011CB505101).
文摘Objective:To investigate the diversity of experiences of sadness emotion and physiological responses among female college students with high neuroticism (HN) and low neuroticism (LN) during the late luteal phase (LLP) and early follicular phase (EFP).Methods:Forty-two participants were classified as the HN group and 41 as the LN group based on their neuroticism score (Eysenck Personality Questionnaire Short Scale for Chinese).Participants watched sadness-inducing experimental films during the LLP and EFP.Results:The HN group showed similar sadness intensities in both phases.The LN group showed higher sadness intensity in the LLP than the EFP.The LN group's sadness scale assessments were lower than the HN group in both phases.The blood volume pulse in the HN group fell in both the LLP and EFP (both P <.001).The root mean square standard deviation of NN intervals rose in the EFP in the HN group before and after watching experimental films (P =.027),but fell in the LN group (P >.05).Between-group comparisons showed heart rate was significantly lower in the HN group than the LN group during EFP (P =.009),but there were no statistically significant differences in subjective experience and physiological data during LLP.The HN group had stronger sadness feelings and greater sadness arousal than the LN group during EFP.There were significant associations between menstrual cycle-related changes in sadness ratings and changes in physiological outcomes.Conclusion:Women with HN have less fluctuation in sadness than those with LN during the menstrual cycle,but experience strong sadness feelings in the LLP.Women with HN show stronger physiological responses in the EFP than those with LN,and have the highest responses in the LLP.
基金supported by grants from the National Natural Science Foundation of China(No.81872804)Sichuan major science and technology project on biotechnology and medicine(No.2018SZDZX0018).
文摘Breast cancer and metastasis remain great challenges in clinical therapy.Compared with monotherapy,combination therapy,especially mediated by nanomedicine delivery strategy,significantly improves the therapeutic efficacy and reduces undesired toxicity.Cyclooxygenase-2(COX-2)inhibitors are widely used for adjuvant chemotherapy because COX-2 is overexpressed in virtually all cancer cell lines to regulate tumor progression by catalyzing prostaglandin E2(PGE2)synthesis.This drug combination strategy is still required to be improved due to some unsatisfactory clinical trial results.Intricate processes of tumor growth and metastasis are orchestrated by multiple proteins in addition to COX-2,which are modified and transported by Golgi apparatus.Hence,disrupting the structure and function of Golgi apparatus can inhibit the secretion of tumor-related proteins and further suppress carcinoma progression and metastasis.Since COX-2 is also enriched within Golgi apparatus in tumor cells,COX-2 inhibitors and Golgi disrupting agents can be co-delivered to Golgi apparatus to maximize the synergy.In this work,we developed a human serum albumin(HSA)nanoparticle encapsulating pirarubicin(THP),retinoic acid(RA),and indomethacin(IMC),called TIR-HSA,which was observed to be localized in Golgi complex of 4T1 cells.Owing to the synergistic effect of these three drugs,TIR-HSA inhibited the proliferation,migration,and invasion of tumor cells,enhanced the apoptotic rate,and improved the immunosuppressive tumor microenvironment,which remarkably regressed the tumor growth and metastasis and prolonged the survival period of 4T1-bearing mice.
