The healing of diabetic wounds poses a significant healthcare burden due to persistent inflammation,M1 macrophage aggregation,and high glucose levels in the microenvironment.Previous studies have demonstrated that imm...The healing of diabetic wounds poses a significant healthcare burden due to persistent inflammation,M1 macrophage aggregation,and high glucose levels in the microenvironment.Previous studies have demonstrated that immunomodulatory hydrogel dressings can facilitate diabetic wound healing.However,current immunomodulatory hydrogels require costly and complex treatments such as cell therapy and cytokines.Herein,a hierarchical hydrogel dressing with continuous biochemical gradient based on glycyrrhizic acid(GA) was constructed to modulate immunomodulatory processes in diabetic wounds.The hydrogels present many desirable features,such as tunable mechanical properties,broad antibacterial ability,outstanding conductive,transparent,and self-adhesive properties.The resultant hydrogel can promote diabetic wound healing by preventing bacterial infection,promoting macrophage polarization,improving the inflammatory microenvironment,and inducing angiogenesis and neurogenesis.Furthermore,electrical stimulation(ES) can further promote the healing of chronic diabetic wounds,providing valuable guidance for relevant clinical practice.展开更多
背景:已有研究发现益生菌对种植体周炎具有一定的防治作用,并在抗种植体周炎的机制研究方面也有进一步的探索。目的:综述益生菌在治疗种植体周炎中的作用机制及临床应用。方法:检索PubMed、Web of Science、中国知网、万方数据库中的相...背景:已有研究发现益生菌对种植体周炎具有一定的防治作用,并在抗种植体周炎的机制研究方面也有进一步的探索。目的:综述益生菌在治疗种植体周炎中的作用机制及临床应用。方法:检索PubMed、Web of Science、中国知网、万方数据库中的相关文献,中文检索词为“益生菌,种植体周炎,菌群失调,免疫调节,炎症反应,微生态平衡”,英文检索词为“Probiotics,Peri-implantitis,Flora imbalance,Immunoregulation,Inflammatory reaction,Mechanism of action”,最终纳入90篇文献进行综述。结果与结论:益生菌具有以下作用机制:可以抑制炎症因子的分泌、促进抗炎因子的产生,从而激活抗炎机制;能够通过分泌微生物的复合物和细菌素来破坏致病菌的细胞壁,降低生物膜的pH值,改善微生态内微生物的组成,以诱导细菌群落结构的变化,从而恢复种植体周微生物群平衡;具有免疫调节作用,它们可以增强宿主口腔黏膜对种植体周围区域致病菌的抵抗力,还能产生抗菌化合物抵消致病微生物的黏附,调节免疫功能。通过上述机制,益生菌在种植体周炎的辅助治疗中具有一定的潜力,能够改善种植体周炎的临床参数并对微生物群产生影响。益生菌为防止种植体周炎提供了一种可供选择的治疗方法,但需要更多的长期前瞻性研究来进一步验证其作用效果。展开更多
Summary： Although mesenchymal stem cells （MSCs） are increasingly used to treat graft-versus-host disease （GVHD）, their immune regulatory mechanism in the process is elusive. The present study aimed to investigate...Summary： Although mesenchymal stem cells （MSCs） are increasingly used to treat graft-versus-host disease （GVHD）, their immune regulatory mechanism in the process is elusive. The present study aimed to investigate the curative effect of third-party umbilical cord blood-derived human MSCs （UCB-hMSCs） on GVHD patients after allogeneic hematopoietic stem cell transplantation （allo-HSCT） and their immune regulatory mechanism. Twenty-four refractory GVHD patients after allo-HSCT were treated with UCB-hMSCs. Immune cells including T lymphocyte subsets, NK ceils, Treg cells and dendritic cells （DCs） and cytokines including interleukin-17 （IL-17） and tumor necrosis factor-alpha （TNF-α） were monitored before and after MSCs transfusion. The results showed that the symptoms of GVHD were alleviated significantly without increased relapse of primary disease and transplant-related complications after MSCs transfusion. The number of CD3^＋, CD3＋CD4^＋ and CD3＋CD8^＋ cells decreased significantly, and that of NK cells remained unchanged, whereas the number of CD4^＋ and CD8^＋ Tregs increased and reached a peak at 4 weeks; the number of mature DCs, and the levels of TNF-α and IL-17 decreased and reached a trough at 2 weeks. It was concluded that MSCs ameliorate GVHD and spare GVL effect via immunoregulations.展开更多
The most recent outbreak of 2019 novel coronavirus,named as COVID-19,caused pneumonia epidemic in Wuhan with 2121 deaths cases as of February 20th 2020.Identification of effective antiviral agents to combat the novel ...The most recent outbreak of 2019 novel coronavirus,named as COVID-19,caused pneumonia epidemic in Wuhan with 2121 deaths cases as of February 20th 2020.Identification of effective antiviral agents to combat the novel coronavirus is urgently needed.Citrus fruit peel or wild citrus are rich in flavonoids,and clinically documented for roles in relief of cough and promotion of digestive health.Therefore,citrus fruits are assumed to possess antivirus activities or enhance the host immunity.A previous study found that hesperetin could act as a high potent inhibitor of SARS-CoV 3CLpro.We determined six flavonoid compounds’content in three citrus species by using LC-MS technique.The content of naringin and naringenin was at higher levels in pummelo.Hesperetin and hesperidin were highly accumulated in mandarin and sweet orange.The subsequent in vitro and in vivo experiments indicated that naringin could inhibit the expression of the proinflammatory cytokines(COX-2,iNOS,IL-1βand IL-6)induced by LPS in Raw macrophage cell line,and may restrain cytokine through inhibiting HMGB1 expression in a mouse model.The results revealed that naringin may have a potential application for preventing cytokine storm.We simulated molecular docking to predict the binding affinity of those flavonoids to bind Angiotensin-converting enzyme 2(ACE 2),which is a receptor of the coronavirus.Consideration of the potential anti-coronavirus and anti-inflammatory activity of flavonoids,the citrus fruit or its derived phytochemicals are promising in the use of prevention and treatment of SARS-CoV-2 infection.展开更多
Intervertebral disc herniation(IVDH)is a common manifestation of intervertebral disc degeneration(IVDD)characterized by inflammation that results in the rupture of the annulus fibrosus(AF)and her-niation of the nucleu...Intervertebral disc herniation(IVDH)is a common manifestation of intervertebral disc degeneration(IVDD)characterized by inflammation that results in the rupture of the annulus fibrosus(AF)and her-niation of the nucleus pulposus(NP).While current clinical research primarily focuses on regulating the degenerative NP,the crucial role of the AF in maintaining the mechanical stability and metabolic balance of the intervertebral disc(IVD)has been overlooked.Resolving immunoregulation and AF repair is im-perative to effectively prevent recurrent herniation.Therefore,this study introduces a bioactive sealant(OD/GM/QCS-sEVs),which combines gelatin methacryloyl(GM)and oxidized dextran(OD)with quater-nized chitosan(QCS)and incorporates small extracellular vesicles(sEVs).The developed sealant possesses injectability,self-healing capabilities,tissue adhesiveness,and mechanical stability,with an average ad-hesive strength of 109.63 kPa.In vitro experiments demonstrate that OD/GM/QCS-sEVs effectively seal AF defects while preserving mechanical properties comparable to those of a normal IVD.Additionally,the sealant releases sEVs through a pH-responsive mechanism,thereby modulating macrophage polarization to the M2 phenotype via the NF-κB signaling pathway.This mechanism facilitates immunoregulation and anti-inflammatory effects,and promotes stem cell differentiation into fibrocartilage.Animal experiments confirm the ability of OD/GM/QCS-sEVs to seal defects,prevent proteoglycan loss,inhibit IVDD develop-ment,and promote AF regeneration.Overall,OD/GM/QCS-sEVs hold promise as an innovative bioactive sealant for recurrent herniation by resolving immunoregulation and AF regeneration.展开更多
基金supported by Natural Science Foundation of Jilin Province(No.SKL202302002)。
文摘The healing of diabetic wounds poses a significant healthcare burden due to persistent inflammation,M1 macrophage aggregation,and high glucose levels in the microenvironment.Previous studies have demonstrated that immunomodulatory hydrogel dressings can facilitate diabetic wound healing.However,current immunomodulatory hydrogels require costly and complex treatments such as cell therapy and cytokines.Herein,a hierarchical hydrogel dressing with continuous biochemical gradient based on glycyrrhizic acid(GA) was constructed to modulate immunomodulatory processes in diabetic wounds.The hydrogels present many desirable features,such as tunable mechanical properties,broad antibacterial ability,outstanding conductive,transparent,and self-adhesive properties.The resultant hydrogel can promote diabetic wound healing by preventing bacterial infection,promoting macrophage polarization,improving the inflammatory microenvironment,and inducing angiogenesis and neurogenesis.Furthermore,electrical stimulation(ES) can further promote the healing of chronic diabetic wounds,providing valuable guidance for relevant clinical practice.
文摘背景:已有研究发现益生菌对种植体周炎具有一定的防治作用,并在抗种植体周炎的机制研究方面也有进一步的探索。目的:综述益生菌在治疗种植体周炎中的作用机制及临床应用。方法:检索PubMed、Web of Science、中国知网、万方数据库中的相关文献,中文检索词为“益生菌,种植体周炎,菌群失调,免疫调节,炎症反应,微生态平衡”,英文检索词为“Probiotics,Peri-implantitis,Flora imbalance,Immunoregulation,Inflammatory reaction,Mechanism of action”,最终纳入90篇文献进行综述。结果与结论:益生菌具有以下作用机制:可以抑制炎症因子的分泌、促进抗炎因子的产生,从而激活抗炎机制;能够通过分泌微生物的复合物和细菌素来破坏致病菌的细胞壁,降低生物膜的pH值,改善微生态内微生物的组成,以诱导细菌群落结构的变化,从而恢复种植体周微生物群平衡;具有免疫调节作用,它们可以增强宿主口腔黏膜对种植体周围区域致病菌的抵抗力,还能产生抗菌化合物抵消致病微生物的黏附,调节免疫功能。通过上述机制,益生菌在种植体周炎的辅助治疗中具有一定的潜力,能够改善种植体周炎的临床参数并对微生物群产生影响。益生菌为防止种植体周炎提供了一种可供选择的治疗方法,但需要更多的长期前瞻性研究来进一步验证其作用效果。
基金supported by grants from the National Natural Science Foundation of China(No.81172826)Collaborative Innovation Center of Hematology,China
文摘Summary： Although mesenchymal stem cells （MSCs） are increasingly used to treat graft-versus-host disease （GVHD）, their immune regulatory mechanism in the process is elusive. The present study aimed to investigate the curative effect of third-party umbilical cord blood-derived human MSCs （UCB-hMSCs） on GVHD patients after allogeneic hematopoietic stem cell transplantation （allo-HSCT） and their immune regulatory mechanism. Twenty-four refractory GVHD patients after allo-HSCT were treated with UCB-hMSCs. Immune cells including T lymphocyte subsets, NK ceils, Treg cells and dendritic cells （DCs） and cytokines including interleukin-17 （IL-17） and tumor necrosis factor-alpha （TNF-α） were monitored before and after MSCs transfusion. The results showed that the symptoms of GVHD were alleviated significantly without increased relapse of primary disease and transplant-related complications after MSCs transfusion. The number of CD3^＋, CD3＋CD4^＋ and CD3＋CD8^＋ cells decreased significantly, and that of NK cells remained unchanged, whereas the number of CD4^＋ and CD8^＋ Tregs increased and reached a peak at 4 weeks; the number of mature DCs, and the levels of TNF-α and IL-17 decreased and reached a trough at 2 weeks. It was concluded that MSCs ameliorate GVHD and spare GVL effect via immunoregulations.
基金supported by the National Key Research and Development Program (2018YFD1000200)Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine (ZYYCXTD-D-202005)the Ability Establishment of Sustainable Use for Valuable Chinese Medicine Resources (2060302).
文摘The most recent outbreak of 2019 novel coronavirus,named as COVID-19,caused pneumonia epidemic in Wuhan with 2121 deaths cases as of February 20th 2020.Identification of effective antiviral agents to combat the novel coronavirus is urgently needed.Citrus fruit peel or wild citrus are rich in flavonoids,and clinically documented for roles in relief of cough and promotion of digestive health.Therefore,citrus fruits are assumed to possess antivirus activities or enhance the host immunity.A previous study found that hesperetin could act as a high potent inhibitor of SARS-CoV 3CLpro.We determined six flavonoid compounds’content in three citrus species by using LC-MS technique.The content of naringin and naringenin was at higher levels in pummelo.Hesperetin and hesperidin were highly accumulated in mandarin and sweet orange.The subsequent in vitro and in vivo experiments indicated that naringin could inhibit the expression of the proinflammatory cytokines(COX-2,iNOS,IL-1βand IL-6)induced by LPS in Raw macrophage cell line,and may restrain cytokine through inhibiting HMGB1 expression in a mouse model.The results revealed that naringin may have a potential application for preventing cytokine storm.We simulated molecular docking to predict the binding affinity of those flavonoids to bind Angiotensin-converting enzyme 2(ACE 2),which is a receptor of the coronavirus.Consideration of the potential anti-coronavirus and anti-inflammatory activity of flavonoids,the citrus fruit or its derived phytochemicals are promising in the use of prevention and treatment of SARS-CoV-2 infection.
基金supported by the National Natural Science Foundation of China(Grant Nos.51873069,52272276,52073103,52203164)the Zhongshan Innovation Project of high-end Scientific Research Institutions(Grant No.2020AG020)+2 种基金the Key-Area Research and Development Program of Guangdong Province(No.2020B090924004)Beijing Municipal Health Commission(Grant Nos.BMHC-2018-4,BMHC-2019-9,PXM2020026275000002)the Postdoctoral Research Foundation of China(No.2022M711183).
文摘Intervertebral disc herniation(IVDH)is a common manifestation of intervertebral disc degeneration(IVDD)characterized by inflammation that results in the rupture of the annulus fibrosus(AF)and her-niation of the nucleus pulposus(NP).While current clinical research primarily focuses on regulating the degenerative NP,the crucial role of the AF in maintaining the mechanical stability and metabolic balance of the intervertebral disc(IVD)has been overlooked.Resolving immunoregulation and AF repair is im-perative to effectively prevent recurrent herniation.Therefore,this study introduces a bioactive sealant(OD/GM/QCS-sEVs),which combines gelatin methacryloyl(GM)and oxidized dextran(OD)with quater-nized chitosan(QCS)and incorporates small extracellular vesicles(sEVs).The developed sealant possesses injectability,self-healing capabilities,tissue adhesiveness,and mechanical stability,with an average ad-hesive strength of 109.63 kPa.In vitro experiments demonstrate that OD/GM/QCS-sEVs effectively seal AF defects while preserving mechanical properties comparable to those of a normal IVD.Additionally,the sealant releases sEVs through a pH-responsive mechanism,thereby modulating macrophage polarization to the M2 phenotype via the NF-κB signaling pathway.This mechanism facilitates immunoregulation and anti-inflammatory effects,and promotes stem cell differentiation into fibrocartilage.Animal experiments confirm the ability of OD/GM/QCS-sEVs to seal defects,prevent proteoglycan loss,inhibit IVDD develop-ment,and promote AF regeneration.Overall,OD/GM/QCS-sEVs hold promise as an innovative bioactive sealant for recurrent herniation by resolving immunoregulation and AF regeneration.
