Objective: Heat shock factor 1(HSF1), a transcriptional regulator of heat shock proteins(HSPs), is an attractive therapeutic target for cancer. However, only a few HSF1 inhibitors have been identified so far.Methods: ...Objective: Heat shock factor 1(HSF1), a transcriptional regulator of heat shock proteins(HSPs), is an attractive therapeutic target for cancer. However, only a few HSF1 inhibitors have been identified so far.Methods: The mRNA and protein levels of HSF1, HSPs, cleaved PARP, and phosphorylated HSF1 were examined by real-time PCR and Western blot. Forced expression, RNA interference, and immunofluorescence assay were used for mechanistic studies.Cell viability and apoptosis were measured by WST-8 assay and flow cytometry, respectively. Xenograft studies were performed in nude mice to evaluate the effect of dorsomorphin and an HSP90 inhibitor on tumor growth.Results: Dorsomorphin suppressed multiple stimuli-induced and constitutive HSPs expression in cancer cells. Mechanistic studies revealed that dorsomorphin reduced heat-induced HSP expression independent of adenosine monophosphate activated protein kinase. Dorsomorphin reduced heat-stimulated HSF1 Ser320 phosphorylation and nuclear translocation, as well as resting nuclear HSF1 levels in cancer cells. Dorsomorphin induced cancer cell apoptosis by inhibiting HSF1 expression. A structure-activity study revealed that the 4-pyridyl at the 3-site of the pyrazolo [1, 5-a]pyrimidine ring is critical for the anti-HSF1 activities of dorsomorphin. Dorsomorphin sensitized cancer cells to HSP90 and proteasome inhibitors and inhibited HSP70 expression induced by these inhibitors in vitro. In tumor-bearing nude mice, dorsomorphin enhanced HSP90 inhibitor-induced cancer cell apoptosis, tumor growth inhibition, and HSP70 expression.Conclusions: Dorsomorphin is an HSF1 inhibitor. It induces cancer cell apoptosis, sensitizes cancer cells to both HSP90 and proteasome inhibitors, and suppresses HSP upregulation by these drugs, which may prevent the development of drug resistance.Hence, dorsomorphin and its derivates may serve as potential precursors for developing drugs against cancer.展开更多
β-Sitosterol-D-glucoside(β-SDG)is a phytosterol compound whose antitumor activity has been confirmed by previous studies.However,its suppression on breast cancer remains unclear.To that purpose,we isolatedβ-SDG fro...β-Sitosterol-D-glucoside(β-SDG)is a phytosterol compound whose antitumor activity has been confirmed by previous studies.However,its suppression on breast cancer remains unclear.To that purpose,we isolatedβ-SDG from sweet potato and investigated the breast-cancer-inhibiting mechanism using proteomic analysis.The sweet potato species S6 with highβ-SDG content were chosen form 36 species andβ-SDG was isolated by HPLC.Afterwards,an in situ animal model of breast cancer was established,andβ-SDG significantly reduced the tumor volume of MCF-7 xenograft mice.Proteomic analysis of tumor tissues revealed that 127 of these proteins were upregulated and 80 were downregulated.Gene ontology and network analysis showed that regulatory proteins were mainly associated with epithelial-mesenchymal transition(EMT),myogenesis,cholesterol homeostasis,oxidative phosphorylation and reactive oxygen pathways,while Vimentin,NDUF,VDAC1,PPP2CA and SNx9 were the most significant 5 node degree genes.Meanwhile,in vitro and in vivo results showed that the protein expression of PPP2CA and Vimentin,which are markers of EMT,were involved in breast cancer cell metastasis and could be reversed byβ-SDG.This work highlightsβ-SDG as a bioactive compound in sweet potato and the potential therapeutic effect ofβ-SDG for the treatment of breast cancer by inhibiting metastasis.展开更多
As a kind of green concrete,the mechanical properties and durability of cemented gangue backfill material(CGBM)will be affected if they are in acid mine water with sulfate ions in the long term.To improve the performa...As a kind of green concrete,the mechanical properties and durability of cemented gangue backfill material(CGBM)will be affected if they are in acid mine water with sulfate ions in the long term.To improve the performance of CGBM in acid mine water with sulfate ions,CGBM specimens with different doses of barium hydroxide were immersed in sulfuric acid solutions of different concentrations for 270 days.The changes of mass,ultrasonic pulse velocity(UPV)and compressive strength of the specimens at different ages were analyzed.Scanning electron microscopy(SEM)and X-ray diffraction(XRD)were used to analyze the microstructure and composition of the specimens.The results show that incorporation of barium hydroxide into CGBM specimen can promote the formation of barium sulfate precipitation and inhibit the generation of corrosion products such as ettringite.Meanwhile,barium sulfate precipitation blocks the pore channel invaded by sulfuric acid solution,delaying the progress of corrosion reaction and making the interior of CGBM specimen more complete.And the specimen with 2.0 kg/m^(3)barium hydroxide was more effective in improving performance.This study provides a basis for the ratio design of CGBM in acid mine water with sulfate ions.展开更多
Mesenchymal stem cells(MSCs)are pluripotent stem cells isolated from human tissues.Due to their strong self-renewal capacity,pluripotency,and immunomodulatory properties,MSCs have garnered significant attention in cel...Mesenchymal stem cells(MSCs)are pluripotent stem cells isolated from human tissues.Due to their strong self-renewal capacity,pluripotency,and immunomodulatory properties,MSCs have garnered significant attention in cell therapy and tissue regeneration.However,cellular senescence induced by replication or external stimuli can impair MSC proliferation and differentiation,making it crucial to develop interventions that delay or reverse the senescence process.From a traditional Chinese medicine perspective,senescence stems from spleen and stomach deficiency,kidney deficiency,and related factors;thus,medicines that tonify the kidney and promote Qi and blood circulation play vital roles in anti-senescence therapy.Chinese medicine,characterized by low toxicity and multi-target,multi-functional properties,has become prominent in anti-senescence research.This paper examines the MSC senescence process by discussing its causes,characteristics,and mechanisms,then summarizes how active ingredients in herbal medicines and natural compounds reverse MSC senescence,facilitating the discovery of additional anti-senescence Chinese medicines and their effective components.展开更多
基金supported by grants from the National Key Research and Development Program of China (Grant No.2017YFC1601702)China Postdoctoral Science Foundation (Grant No.2011M500825)
文摘Objective: Heat shock factor 1(HSF1), a transcriptional regulator of heat shock proteins(HSPs), is an attractive therapeutic target for cancer. However, only a few HSF1 inhibitors have been identified so far.Methods: The mRNA and protein levels of HSF1, HSPs, cleaved PARP, and phosphorylated HSF1 were examined by real-time PCR and Western blot. Forced expression, RNA interference, and immunofluorescence assay were used for mechanistic studies.Cell viability and apoptosis were measured by WST-8 assay and flow cytometry, respectively. Xenograft studies were performed in nude mice to evaluate the effect of dorsomorphin and an HSP90 inhibitor on tumor growth.Results: Dorsomorphin suppressed multiple stimuli-induced and constitutive HSPs expression in cancer cells. Mechanistic studies revealed that dorsomorphin reduced heat-induced HSP expression independent of adenosine monophosphate activated protein kinase. Dorsomorphin reduced heat-stimulated HSF1 Ser320 phosphorylation and nuclear translocation, as well as resting nuclear HSF1 levels in cancer cells. Dorsomorphin induced cancer cell apoptosis by inhibiting HSF1 expression. A structure-activity study revealed that the 4-pyridyl at the 3-site of the pyrazolo [1, 5-a]pyrimidine ring is critical for the anti-HSF1 activities of dorsomorphin. Dorsomorphin sensitized cancer cells to HSP90 and proteasome inhibitors and inhibited HSP70 expression induced by these inhibitors in vitro. In tumor-bearing nude mice, dorsomorphin enhanced HSP90 inhibitor-induced cancer cell apoptosis, tumor growth inhibition, and HSP70 expression.Conclusions: Dorsomorphin is an HSF1 inhibitor. It induces cancer cell apoptosis, sensitizes cancer cells to both HSP90 and proteasome inhibitors, and suppresses HSP upregulation by these drugs, which may prevent the development of drug resistance.Hence, dorsomorphin and its derivates may serve as potential precursors for developing drugs against cancer.
基金supported by Special Key project of Technology Innovation and Application Development in Chongqing(CSTC2021jscx-gksb-N0033,CSTB2021TIAD-KPX0085)Science Foundation of School of Life Sciences SWU(20212005425201)County-University Cooperation Innovation Funds of Southwest University(SZ202102).
文摘β-Sitosterol-D-glucoside(β-SDG)is a phytosterol compound whose antitumor activity has been confirmed by previous studies.However,its suppression on breast cancer remains unclear.To that purpose,we isolatedβ-SDG from sweet potato and investigated the breast-cancer-inhibiting mechanism using proteomic analysis.The sweet potato species S6 with highβ-SDG content were chosen form 36 species andβ-SDG was isolated by HPLC.Afterwards,an in situ animal model of breast cancer was established,andβ-SDG significantly reduced the tumor volume of MCF-7 xenograft mice.Proteomic analysis of tumor tissues revealed that 127 of these proteins were upregulated and 80 were downregulated.Gene ontology and network analysis showed that regulatory proteins were mainly associated with epithelial-mesenchymal transition(EMT),myogenesis,cholesterol homeostasis,oxidative phosphorylation and reactive oxygen pathways,while Vimentin,NDUF,VDAC1,PPP2CA and SNx9 were the most significant 5 node degree genes.Meanwhile,in vitro and in vivo results showed that the protein expression of PPP2CA and Vimentin,which are markers of EMT,were involved in breast cancer cell metastasis and could be reversed byβ-SDG.This work highlightsβ-SDG as a bioactive compound in sweet potato and the potential therapeutic effect ofβ-SDG for the treatment of breast cancer by inhibiting metastasis.
基金sponsored by the National Natural Science Foundation of China(Grant No.51974192)the Distinguished Youth Funds of National Natural Science Foundation of China(Grant No.51925402)Shanxi-Zheda Institute of Advanced Materials and Chemical Engineering Project(2021SX-TD001).
文摘As a kind of green concrete,the mechanical properties and durability of cemented gangue backfill material(CGBM)will be affected if they are in acid mine water with sulfate ions in the long term.To improve the performance of CGBM in acid mine water with sulfate ions,CGBM specimens with different doses of barium hydroxide were immersed in sulfuric acid solutions of different concentrations for 270 days.The changes of mass,ultrasonic pulse velocity(UPV)and compressive strength of the specimens at different ages were analyzed.Scanning electron microscopy(SEM)and X-ray diffraction(XRD)were used to analyze the microstructure and composition of the specimens.The results show that incorporation of barium hydroxide into CGBM specimen can promote the formation of barium sulfate precipitation and inhibit the generation of corrosion products such as ettringite.Meanwhile,barium sulfate precipitation blocks the pore channel invaded by sulfuric acid solution,delaying the progress of corrosion reaction and making the interior of CGBM specimen more complete.And the specimen with 2.0 kg/m^(3)barium hydroxide was more effective in improving performance.This study provides a basis for the ratio design of CGBM in acid mine water with sulfate ions.
基金supported by Zhejiang Provincial Natural Science Foundation of China(No.LQ23H290006)the National Natural Science Foundation of China(No.82204781)+2 种基金the Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province(No.2020E10021)Zhejiang Provincial Program for the Cultivation of High-level Innovative Health Talents(No.ZWB-2020-18)Zhejiang Provincial Traditional Chinese Medicine Science and Technology Project(No.2023ZR119).
文摘Mesenchymal stem cells(MSCs)are pluripotent stem cells isolated from human tissues.Due to their strong self-renewal capacity,pluripotency,and immunomodulatory properties,MSCs have garnered significant attention in cell therapy and tissue regeneration.However,cellular senescence induced by replication or external stimuli can impair MSC proliferation and differentiation,making it crucial to develop interventions that delay or reverse the senescence process.From a traditional Chinese medicine perspective,senescence stems from spleen and stomach deficiency,kidney deficiency,and related factors;thus,medicines that tonify the kidney and promote Qi and blood circulation play vital roles in anti-senescence therapy.Chinese medicine,characterized by low toxicity and multi-target,multi-functional properties,has become prominent in anti-senescence research.This paper examines the MSC senescence process by discussing its causes,characteristics,and mechanisms,then summarizes how active ingredients in herbal medicines and natural compounds reverse MSC senescence,facilitating the discovery of additional anti-senescence Chinese medicines and their effective components.
