Background:Theanine,was natural compounds,has been employed in antibacterial,antineoplastic,promotion of hair growth,therapy of poliosis,and removing pattogenic heat from the blood and toxic material from the body for...Background:Theanine,was natural compounds,has been employed in antibacterial,antineoplastic,promotion of hair growth,therapy of poliosis,and removing pattogenic heat from the blood and toxic material from the body for centuries.However,few reports focused on the treatment by theanine combined with chemotherapy in triple negative breast cancer.Methods:Our study aimed to evaluate and compare the molecular and cellular effects of theanine in combination with cisplatin in triple negative breast cancer lines MDA-MB-231.The 50%inhibitory concentration and cell viability were determined by the cell counting kit-8 assay.Meanwhile,wound healing and transwell assays were used to evaluate the effect of theanine combination with cisplatin on triple negative breast cancer(TNBC)cell metastasis.Moreover,the label-free proteomic method was available to explore the molecular mechanism of theanine combination with cisplatin on TNBC cells.What’s more,reverse transcription-polymerase chain reaction and western blotting were carried out to evaluate the related protein and mRNA alteration in the Akt signaling pathway.Results:With theanine added,the inhibitory effect of cisplatin on cell proliferation and metastasis was significantly improved.Meanwhile,with the increase of theanine concentration,the anti-tumor effect of the combination group was also significantly improved.Afterward,label-free proteomics analysis showed that theanine combined with cisplatin could significantly activate the Akt signaling pathway,thus improving the anti-tumor effect of cisplatin.Finally,reverse transcription-polymerase chain reaction and western blotting experiment showed that the combination of cisplatin with theanine induced the greatest down-regulation of phosphorylated Akt expression.Conclusion:All in all,combining theanine with appears to be a promising strategy for the effective treatment of TNBC in the prospective application which merits further clinical investigation.展开更多
Limited by the tiny structure of axons,the effects of these axonal hyperpolarizing inputs on neuronal activity have not been directly elucidated.Here,we imitated these processes by simultaneously recording the activit...Limited by the tiny structure of axons,the effects of these axonal hyperpolarizing inputs on neuronal activity have not been directly elucidated.Here,we imitated these processes by simultaneously recording the activities of the somas and proximal axons of cortical pyramidal neurons.We found that spikes and subthreshold potentials propagate between somas and axons with high fidelity.Furthermore,inhibitory inputs on axons have opposite effects on neuronal activity according to their temporal integration with upstream signals.Concurrent with somatic depolarization,inhibitory inputs on axons decrease neuronal excitability and impede spike generation.In addition,following action potentials,inhibitory inputs on an axon increase neuronal spike capacity and improve spike precision.These results indicate that inhibitory inputs on proximal axons have dual regulatory functions in neuronal activity（suppression or facilitation）according to neuronal network patterns.展开更多
Objective:To explore the mechanism of tapinarof inhibiting proliferation and promoting apoptosis of non-small cell lung cancer A549 cell.Methods:The proliferative ability of non-small cell lung cancer cells A549 and H...Objective:To explore the mechanism of tapinarof inhibiting proliferation and promoting apoptosis of non-small cell lung cancer A549 cell.Methods:The proliferative ability of non-small cell lung cancer cells A549 and H1299 was detected by clonal formation assay,and the cell viability of non-small cell lung cancer cells A549 was detected by CCK-8 assay.A549 cells were treated with different concentrations of tapinarof(0,5,10,20)μmol/L for 24 h.The effects of tapinarof on the cell cycle of A549 were detected by flow cytometry using PI single dye method.Western blot assay was used to detect the effect of benzene-moder on the expression of cycle-associated protein P21 and CDK2.A549 cells were treated with different concentrations of tapinarof(0,10,20,40)μmol/L for 48 h.Annexin V-FITC and PI double staining were used to detect the effect of tapinarof on apoptosis of A549 cells.Western blot assay was used to detect the effects of different concentrations of tapinarof on expression of apoptosis-related proteins,cleaved-caspase 3 and cleaved-PARP.Western blot analysis was performed to determine the expression of p-AKT and FOXO1 in A549 cells at different concentrations(0,5,10,20)μmol/L.Results:The results of clonal formation experiment showed that 40μmol/L tapinarof could completely inhibit the proliferation of A549 and H1299 cells.CCK-8 assay showed that compared with the control group(0μmol/L),A549 cell activity decreased gradually with the increase of tapinarof concentration.A549 cells were stained with Annexin-FITC/PI.Flow cytometry showed that the apoptosis rate of A549 cells increased with the increase of tapinarof treatment concentration(40μmol/L tapinarof treatment,P<0.001).After treatment with tapinarof for 48 h,the protein expression of cleaved-caspase 3 and cleaved-PARP in A549 cells was increased,compared with control group(0μmol/L).Flow cytometry after PI staining of A549 cells showed that tapinarof induced A549 cell arrest in G1 phase.In A549 cells treated with tapinarof for 24 h,the expression of P21 protein was increased and CDK2 decreased.The phosphorylation level of AKT was significantly inhibited and the expression level of FOXO1 was increased in A549 cells treated with phenylenmode at different concentrations.Conclusion:Tapinarof inhibits the proliferation of A549 cells and induces apoptosis,which may be related to the AKT/FOXO1 signaling pathway.展开更多
BACKGROUND Hepatic cysts are common benign liver tumors that are typically asymptomatic.However,larger cysts,particularly giant liver cysts,can potentially induce symptoms.If the diameter of the cyst exceeds 10 cm,it ...BACKGROUND Hepatic cysts are common benign liver tumors that are typically asymptomatic.However,larger cysts,particularly giant liver cysts,can potentially induce symptoms.If the diameter of the cyst exceeds 10 cm,it can exert pressure on adjacent organs,leading to manifestations of corresponding symptoms.Here,we report the case of a complex giant hepatic cyst that caused pseudocystitis.CASE SUMMARY A 16-year-old girl was admitted to our hospital with frequent and urgent urination.Ultrasonography revealed no obvious uterine adnexal abnormalities but showed a hypoechoic,cystic mass(173 mm×84 mm×138 mm)with clear boundaries,and an unclear blood flow signal in the abdominal cavity(extending from the lower edge of the left lobe of liver to the upper edge of the bladder).Abdominal contrast-enhanced computed tomography revealed a giant cystic mass in the abdominal and pelvic cavities,possibly originating from the liver,and a small amount of free fluid in the pelvic cavity,which subsequent magnetic resonance imaging confirmed.The imaging characteristics were consistent with a benign lesion.The patient underwent laparoscopic resection of the giant liver cyst with partial liver resection.Post-surgery her symptoms urinary symptoms were relieved completely and she was discharged on the sixth postoperative day.CONCLUSION Our patient presented with symptoms suggestive of pseudocystitis,stressing the need for considering possibilities of other etiologies and differential diagnoses.展开更多
Macrophages show significant heterogeneity in function and phenotype, which could shift into different populations of cells in response to exposure to various micro-environmental signals. These changes, also termed as...Macrophages show significant heterogeneity in function and phenotype, which could shift into different populations of cells in response to exposure to various micro-environmental signals. These changes, also termed as macrophage polarization, of which play an important role in the pathogenesis of many diseases. Numerous studies have proved that Hesperidin(HDN), a traditional Chinese medicine, extracted from fruit peels of the genus citrus, play key roles in anti-inflammation, anti-tumor, anti-oxidant and so on. However, the role of HDN in macrophage polarization has never been reported. Additional, because of its poor water solubility and bioavailability. Our laboratory had synthesized many hesperidin derivatives. Among them, hesperidin derivatives-12(HDND-12) has better water solubility and bioavailability. So, we evaluated the role of HDND-12 in macrophage polarization in the present study. The results showed that the expression of Arginase-1(Arg-1), interleukin-10(IL-10), transforming growth factor β(TGF-β) were up-regulated by HDND-12, whereas the expression of inducible Nitric Oxide Synthase(iNOS) was down-regulated in LPS-and IFN-γ-treated(M1) RAW264.7 cells. Moreover, the expression of p-JAK2 and p-STAT3 were significantly decreased after stimulation with HDND-12 in M1-like macrophages. More importantly, when we taken AG490(inhibitor of JAK2/STAT3 signaling), the protein levels of iNOS were significantly reduced in AG490 stimulation group compare with control in LPS, IFN-γ and HDND-12 stimulation cells. Taken together, these findings indicated that HDND-12 could prevent polarization toward M1-like macrophages, at least in part, through modulating JAK2/STAT3 pathway.展开更多
There has been increasing interest in the psycho-socio-relational and sexual disorders of infertility,as the risk of psychological burden among in fertile men with sexual dysf un ctio ns is sign ifica nt.The purpose o...There has been increasing interest in the psycho-socio-relational and sexual disorders of infertility,as the risk of psychological burden among in fertile men with sexual dysf un ctio ns is sign ifica nt.The purpose of this study was to develop and to validate a predictive model to estimate in dividual psychological burde n among in fertile men with sexual dysf unction and study the associati on betwee n them.Comprehe nsive data were collected for in fertile men(n=480)who sought treatme nt for infertility in a reproductive medici ne center between June 2012 and December 2013.Using independent predictors of psychological burden from the least absolute shrinkage and selection operator,univariable and multivariable analyses were developed into two models.Predictive accuracy was compared between the models.We explored the association between sexual dysfunction and psychological burden.A total of 480 patie nts were an a lyzed using 10-fold cross-validatio n.In depende nt predictors of psychological burde n were incorporated into a model to measure anxiety(corrected-area under curve(AUC):77.3%)and a model to measure depression(corrected-AUC:70.2%).Anxiety and depression were both associated with erectile dysfunction(P<0.05),with anxiety demonstrating the strongest association.Only anxiety was associated with premature ejaculation(P>0.05).Premature ejaculation was not found to be associated with depression(P>0.05).Predictive models for psychological burden among infertile men with sexual dysfunction are presented,and we found that there is an association between psychological burden and sexual dysfunction.According to the models,proper counseling and treatment of sexual dysfunction in infertile men may reduce the psychological burden,help attain natural pregnancy,and improve the quality of life.展开更多
基金the grants from Project of Schools Directly Under the Wenzhou Municipal Bureau(WX2022056).
文摘Background:Theanine,was natural compounds,has been employed in antibacterial,antineoplastic,promotion of hair growth,therapy of poliosis,and removing pattogenic heat from the blood and toxic material from the body for centuries.However,few reports focused on the treatment by theanine combined with chemotherapy in triple negative breast cancer.Methods:Our study aimed to evaluate and compare the molecular and cellular effects of theanine in combination with cisplatin in triple negative breast cancer lines MDA-MB-231.The 50%inhibitory concentration and cell viability were determined by the cell counting kit-8 assay.Meanwhile,wound healing and transwell assays were used to evaluate the effect of theanine combination with cisplatin on triple negative breast cancer(TNBC)cell metastasis.Moreover,the label-free proteomic method was available to explore the molecular mechanism of theanine combination with cisplatin on TNBC cells.What’s more,reverse transcription-polymerase chain reaction and western blotting were carried out to evaluate the related protein and mRNA alteration in the Akt signaling pathway.Results:With theanine added,the inhibitory effect of cisplatin on cell proliferation and metastasis was significantly improved.Meanwhile,with the increase of theanine concentration,the anti-tumor effect of the combination group was also significantly improved.Afterward,label-free proteomics analysis showed that theanine combined with cisplatin could significantly activate the Akt signaling pathway,thus improving the anti-tumor effect of cisplatin.Finally,reverse transcription-polymerase chain reaction and western blotting experiment showed that the combination of cisplatin with theanine induced the greatest down-regulation of phosphorylated Akt expression.Conclusion:All in all,combining theanine with appears to be a promising strategy for the effective treatment of TNBC in the prospective application which merits further clinical investigation.
基金supported by the National Natural Science Foundation of China,No.31500836,81671288the Natural Science Foundation of Anhui Province of China,No.1608085QH176
文摘Limited by the tiny structure of axons,the effects of these axonal hyperpolarizing inputs on neuronal activity have not been directly elucidated.Here,we imitated these processes by simultaneously recording the activities of the somas and proximal axons of cortical pyramidal neurons.We found that spikes and subthreshold potentials propagate between somas and axons with high fidelity.Furthermore,inhibitory inputs on axons have opposite effects on neuronal activity according to their temporal integration with upstream signals.Concurrent with somatic depolarization,inhibitory inputs on axons decrease neuronal excitability and impede spike generation.In addition,following action potentials,inhibitory inputs on an axon increase neuronal spike capacity and improve spike precision.These results indicate that inhibitory inputs on proximal axons have dual regulatory functions in neuronal activity（suppression or facilitation）according to neuronal network patterns.
基金Local Science and Technology Development Funds Projects in Anhui Province(No.2020b07030008)。
文摘Objective:To explore the mechanism of tapinarof inhibiting proliferation and promoting apoptosis of non-small cell lung cancer A549 cell.Methods:The proliferative ability of non-small cell lung cancer cells A549 and H1299 was detected by clonal formation assay,and the cell viability of non-small cell lung cancer cells A549 was detected by CCK-8 assay.A549 cells were treated with different concentrations of tapinarof(0,5,10,20)μmol/L for 24 h.The effects of tapinarof on the cell cycle of A549 were detected by flow cytometry using PI single dye method.Western blot assay was used to detect the effect of benzene-moder on the expression of cycle-associated protein P21 and CDK2.A549 cells were treated with different concentrations of tapinarof(0,10,20,40)μmol/L for 48 h.Annexin V-FITC and PI double staining were used to detect the effect of tapinarof on apoptosis of A549 cells.Western blot assay was used to detect the effects of different concentrations of tapinarof on expression of apoptosis-related proteins,cleaved-caspase 3 and cleaved-PARP.Western blot analysis was performed to determine the expression of p-AKT and FOXO1 in A549 cells at different concentrations(0,5,10,20)μmol/L.Results:The results of clonal formation experiment showed that 40μmol/L tapinarof could completely inhibit the proliferation of A549 and H1299 cells.CCK-8 assay showed that compared with the control group(0μmol/L),A549 cell activity decreased gradually with the increase of tapinarof concentration.A549 cells were stained with Annexin-FITC/PI.Flow cytometry showed that the apoptosis rate of A549 cells increased with the increase of tapinarof treatment concentration(40μmol/L tapinarof treatment,P<0.001).After treatment with tapinarof for 48 h,the protein expression of cleaved-caspase 3 and cleaved-PARP in A549 cells was increased,compared with control group(0μmol/L).Flow cytometry after PI staining of A549 cells showed that tapinarof induced A549 cell arrest in G1 phase.In A549 cells treated with tapinarof for 24 h,the expression of P21 protein was increased and CDK2 decreased.The phosphorylation level of AKT was significantly inhibited and the expression level of FOXO1 was increased in A549 cells treated with phenylenmode at different concentrations.Conclusion:Tapinarof inhibits the proliferation of A549 cells and induces apoptosis,which may be related to the AKT/FOXO1 signaling pathway.
文摘BACKGROUND Hepatic cysts are common benign liver tumors that are typically asymptomatic.However,larger cysts,particularly giant liver cysts,can potentially induce symptoms.If the diameter of the cyst exceeds 10 cm,it can exert pressure on adjacent organs,leading to manifestations of corresponding symptoms.Here,we report the case of a complex giant hepatic cyst that caused pseudocystitis.CASE SUMMARY A 16-year-old girl was admitted to our hospital with frequent and urgent urination.Ultrasonography revealed no obvious uterine adnexal abnormalities but showed a hypoechoic,cystic mass(173 mm×84 mm×138 mm)with clear boundaries,and an unclear blood flow signal in the abdominal cavity(extending from the lower edge of the left lobe of liver to the upper edge of the bladder).Abdominal contrast-enhanced computed tomography revealed a giant cystic mass in the abdominal and pelvic cavities,possibly originating from the liver,and a small amount of free fluid in the pelvic cavity,which subsequent magnetic resonance imaging confirmed.The imaging characteristics were consistent with a benign lesion.The patient underwent laparoscopic resection of the giant liver cyst with partial liver resection.Post-surgery her symptoms urinary symptoms were relieved completely and she was discharged on the sixth postoperative day.CONCLUSION Our patient presented with symptoms suggestive of pseudocystitis,stressing the need for considering possibilities of other etiologies and differential diagnoses.
基金supported by the Key Fund Project of Anhui Education Department(No.KJ2016A364)National Natural Science Foundation of China(No.81473268)
文摘Macrophages show significant heterogeneity in function and phenotype, which could shift into different populations of cells in response to exposure to various micro-environmental signals. These changes, also termed as macrophage polarization, of which play an important role in the pathogenesis of many diseases. Numerous studies have proved that Hesperidin(HDN), a traditional Chinese medicine, extracted from fruit peels of the genus citrus, play key roles in anti-inflammation, anti-tumor, anti-oxidant and so on. However, the role of HDN in macrophage polarization has never been reported. Additional, because of its poor water solubility and bioavailability. Our laboratory had synthesized many hesperidin derivatives. Among them, hesperidin derivatives-12(HDND-12) has better water solubility and bioavailability. So, we evaluated the role of HDND-12 in macrophage polarization in the present study. The results showed that the expression of Arginase-1(Arg-1), interleukin-10(IL-10), transforming growth factor β(TGF-β) were up-regulated by HDND-12, whereas the expression of inducible Nitric Oxide Synthase(iNOS) was down-regulated in LPS-and IFN-γ-treated(M1) RAW264.7 cells. Moreover, the expression of p-JAK2 and p-STAT3 were significantly decreased after stimulation with HDND-12 in M1-like macrophages. More importantly, when we taken AG490(inhibitor of JAK2/STAT3 signaling), the protein levels of iNOS were significantly reduced in AG490 stimulation group compare with control in LPS, IFN-γ and HDND-12 stimulation cells. Taken together, these findings indicated that HDND-12 could prevent polarization toward M1-like macrophages, at least in part, through modulating JAK2/STAT3 pathway.
基金the National Natural Science Foundation of China(81871110,81471449,81671449)the Fundamental Research Funds for the Central Universities(18ykpy09)+4 种基金the Natural Science Foundation Key Program of Guangdong Province(2018B030311039)the Science and Technology Planning Project of Guangdong Province(2016A040403113,2016B030230001)the Key Scientific and Technological Program of Guangzhou City(201604020189)Natural Science Research Project of Anhui Province Education Department(KJ2018A0989)HMC would like to thank Qian-Nan Yang for her support and the reviewers for their valuable comments.
文摘There has been increasing interest in the psycho-socio-relational and sexual disorders of infertility,as the risk of psychological burden among in fertile men with sexual dysf un ctio ns is sign ifica nt.The purpose of this study was to develop and to validate a predictive model to estimate in dividual psychological burde n among in fertile men with sexual dysf unction and study the associati on betwee n them.Comprehe nsive data were collected for in fertile men(n=480)who sought treatme nt for infertility in a reproductive medici ne center between June 2012 and December 2013.Using independent predictors of psychological burden from the least absolute shrinkage and selection operator,univariable and multivariable analyses were developed into two models.Predictive accuracy was compared between the models.We explored the association between sexual dysfunction and psychological burden.A total of 480 patie nts were an a lyzed using 10-fold cross-validatio n.In depende nt predictors of psychological burde n were incorporated into a model to measure anxiety(corrected-area under curve(AUC):77.3%)and a model to measure depression(corrected-AUC:70.2%).Anxiety and depression were both associated with erectile dysfunction(P<0.05),with anxiety demonstrating the strongest association.Only anxiety was associated with premature ejaculation(P>0.05).Premature ejaculation was not found to be associated with depression(P>0.05).Predictive models for psychological burden among infertile men with sexual dysfunction are presented,and we found that there is an association between psychological burden and sexual dysfunction.According to the models,proper counseling and treatment of sexual dysfunction in infertile men may reduce the psychological burden,help attain natural pregnancy,and improve the quality of life.
