According to epidemiological studies,twice as many women as men are affected by irritable bowel syndrome(IBS)in western countries,suggesting a role for sex hormones in IBS pathophysiology.Despite growing evidence abou...According to epidemiological studies,twice as many women as men are affected by irritable bowel syndrome(IBS)in western countries,suggesting a role for sex hormones in IBS pathophysiology.Despite growing evidence about the implications of sex hormones in IBS symptom modulation,data on mechanisms by which they influence disease development are sparse.This review aims to determine the state of knowledge about the role of sex hormones in sensorimotor dysfunctions and to address the possible interplay of sex hormones with common risk factors associated with IBS.The scientific bibliography was searched using the following keywords:irritable bowel syndrome,sex,gender,ovarian hormone,estradiol,progesterone,testosterone,symptoms,pain,sensitivity,motility,permeability,stress,immune system,brain activity,spinal,supraspinal,imaging.Ovarian hormones variations along themenstrual cycle affect sensorimotor gastrointestinal function in both healthy and IBS populations.They can modulate pain processing by interacting with neuromodulator systems and the emotional system responsible for visceral pain perception.These hormones can also modulate the susceptibility to stress,which is a pivotal factor in IBS occurrence and symptom severity.For instance,estrogen-dependent hyper-responsiveness to stress can promote immune activation or impairments of gut barrier function.In conclusion,whereas it is important to keep in mind that ovarian hormones cannot be considered as a causal factor of IBS,they arguably modulate IBS onset and symptomatology.However,our understanding of the underlying mechanisms remains limited and studies assessing the link between IBS symptoms and ovarian hormone levels are needed to improve our knowledge of the disease evolution with regard to gender.Further studies assessing the role of male hormones are also needed to understand fully the role of sex hormones in IBS.Finally,investigation of brain-gut interactions is critical to decipher how stress,ovarian hormones,and female brain processing of pain can translate 展开更多
A series of natural berberine-derived nitroimidazoles as novel antibacterial agents were designed, synthesized and characterized by nuclear magnetic resonance(NMR), infrared spectra(IR), and high resolution mass spect...A series of natural berberine-derived nitroimidazoles as novel antibacterial agents were designed, synthesized and characterized by nuclear magnetic resonance(NMR), infrared spectra(IR), and high resolution mass spectra(HRMS) spectra. The antimicrobial evaluation showed that some target molecules exhibited moderate to good inhibitory activities against the tested bacteria and fungi including clinical drug-resistant strains isolated from infected patients. Especially, 2-fluorobenzyl derivative8 f not only gave strong activity against drug-resistant E. coli with the minimal inhibitory concentration(MIC) value of0.003 m M, 33-fold more active than norfloxacin, but also exhibited low toxicity toward RAW 264.7 cells and less propensity to trigger resistance. The aqueous solubility and Clog P values of target compounds were investigated to elucidate the structureactivity relationships. Molecular docking and quantum chemical studies for compound 8 f rationally explained its antibacterial effect. The further exploration of antibacterial mechanism revealed that the highly active compound 8 f could effectively permeabilize E. coli cell membrane and intercalate into DNA isolated from resistant E. coli to form 8 f-DNA complex that might block DNA replication to exert the powerful bioactivities. Compound 8 f could also selectively address resistant E. coli from a mixture of various strains.展开更多
AIM To investigate the capability of salvianolic acid B(Sal B) to protect hepatocytes from hydrogen peroxide(H_2O_2)/carbon tetrachloride(CCl_4)-induced lysosomal membrane permeabilization. METHODS Cell Counting Kit-8...AIM To investigate the capability of salvianolic acid B(Sal B) to protect hepatocytes from hydrogen peroxide(H_2O_2)/carbon tetrachloride(CCl_4)-induced lysosomal membrane permeabilization. METHODS Cell Counting Kit-8 assay was used to measure cell viability. Apoptosis and death were assayed through flow cytometry. Brd U incorporation was used to detect cell proliferation. Serum alanine aminotransferase activity and liver malondialdehyde(MDA) content were measured. Liver histopathological changes were evaluated using hematoxylin-eosin staining. Lysosomal membrane permeability was detected with Lyso Tracker Green-labeled probes and acridine orange staining. The levels of protein carbonyl content(PCC), cathepsins(Cat)B/D, and lysosome-associated membrane protein 1(LAMP1) were evaluated through western blotting. Cytosol Cat B activity analysis was performed with chemiluminescence detection. The m RNA level ofLAMP1 was evaluated through quantitative real-time polymerase chain reaction. RESULTS Results indicated that H_2O_2 induced cell injury/death. Sal B attenuated H_2O_2-induced cell apoptosis and death, restored the inhibition of proliferation, decreased the amount of PCC, and stabilized the lysosome membrane by increasing the LAMP1 protein level and antagonizing Cat B/D leakage into the cytosol. CCl_4 also triggered hepatocyte death. Furthermore, Sal B effectively rescued hepatocytes by increasing LAMP1 expression and by reducing lysosomal enzyme translocation to the cytosol.CONCLUSION Sal B protected mouse embryonic hepatocytes from H_2O_2/CCl_4-induced injury/death by stabilizing the lysosomal membrane.展开更多
Objective:It has been reported that intrinsic apoptosis is associated with the progression of bladder cancer(BC).Recent evidence suggests that polyribonucleotide nucleotidyltransferase 1(PNPT1)is a pivotal mediator in...Objective:It has been reported that intrinsic apoptosis is associated with the progression of bladder cancer(BC).Recent evidence suggests that polyribonucleotide nucleotidyltransferase 1(PNPT1)is a pivotal mediator involved in RNA decay and cell apoptosis.However,the regulation and roles of PNPT1 in bladder cancer remain largely unclear.Methods:The upstream miRNA regulators were predicted by in silico analysis.The expression levels of PNPT1 were evaluated by real-time PCR,Western blotting,and immunohistochemistry(IHC),while miR-183-5p levels were evaluated by qPCR in BC cell lines and tissues.In vitro and in vivo assays were performed to investigate the function of miR-183-5p and PNPT1 in apoptotic RNA decay and the tumorigenic capability of bladder cancer cells.Results:PNPT1 expression was decreased in BC tissues and cell lines.Overexpression of PNPT1 significantly promoted cisplatin-induced intrinsic apoptosis of BC cells,whereas depletion of PNPT1 potently alleviated these effects.Moreover,oncogenic miR183-5p directly targeted the 3′UTR of PNPT1 and reversed the tumor suppressive role of PNPT1.Intriguingly,miR-183-5p modulated not only PNPT1 but also Bcl2 modifying factor(BMF)to inhibit the mitochondrial outer membrane permeabilization(MOMP)in BC cells.Conclusion:Our results provide new insight into the mechanisms underlying intrinsic apoptosis in BC,suggesting that the miR-183-5p-PNPT1 regulatory axis regulates the apoptosis of BC cells and might represent a potential therapeutic avenue for the treatment of BC.展开更多
Many conventional anticancer drugs have an associated lack of safety by their toxicity. Relatively faster mutations in tumor cells pose a significant obstacle in treatment of cancer. Recently, “Mitocans” have emerge...Many conventional anticancer drugs have an associated lack of safety by their toxicity. Relatively faster mutations in tumor cells pose a significant obstacle in treatment of cancer. Recently, “Mitocans” have emerged as a novel class of anticancer agents selectively targeting tumor cells and thus, are much less toxic than conventional anticancer chemotherapeutic agents. Mitocans are drugs that act directly on mitochondria within the cell, thus causing changes in energy metabolism of the cell. Amongst these mitocans, α-Tocopheryl succinate or vitamin E analogs are studied very well by researchers. This review discusses mitochondrial drug targeting strategies and a variety of novel mitochondrial drug targets of mitocans, such as electron transport chain, mitochondrial permeability transition, Bcl-2 family proteins and mitochondrial DNA. The purpose of this review is to focus on the various classes of mitocans, the mechanisms by which these drugs specifically act on tumor cells and their applications in cancer chemotherapeutics.展开更多
The increased importance of the G. mellonella for wide range of scientific research and commercial sides will need to create a germplasm resource banking by cryopreservation. Impermeability is a fundamental limiting f...The increased importance of the G. mellonella for wide range of scientific research and commercial sides will need to create a germplasm resource banking by cryopreservation. Impermeability is a fundamental limiting factor for the successful cryopreservation of arthropods embryos. The successful permeability of Drosophila embryo by using an embryo permeabilization solvent (EPS) solution encouraged this trial on G. mellonella embryos (stage of 24 hours Post-oviposition (h PO)). Permeability assessment with Rhodamine B and crystal violet dyes showed that G. mellonella embryos can be permeabilized by EPS of D-limonene that has 3 mol ethoxylated alcohol. The permeabilization for 30 sec exposure time was resulted 61.5% ± 5.8% survival rate, 31.7% ± 3.1% uptakes dyes and 40.5% ± 0.3% was the survival rate post loading in 12% Ethylene glycol (EG). The low viability after immersion in liquid nitrogen (LN) (0.6% ± 0.08%) is due to the dual toxicity of EPS and cryoprotectant (CPA) solutions. However, fluorescence images showed sufficient permeability that confirms the possibility to increase the permeability of G. mellonella embryos with EPS solution, and to have the opportunity to improve the viability after LN by improving procedures of loading and dehydration with various CPAs and exposure times, which decrease the toxicity effect.展开更多
We reported previously that chymotrypsin B is cached in the lysosomes of rat hepatocytes and mediates apoptosis induced by TNF-alpha (1) and H2O2. However, the mechanism
文摘According to epidemiological studies,twice as many women as men are affected by irritable bowel syndrome(IBS)in western countries,suggesting a role for sex hormones in IBS pathophysiology.Despite growing evidence about the implications of sex hormones in IBS symptom modulation,data on mechanisms by which they influence disease development are sparse.This review aims to determine the state of knowledge about the role of sex hormones in sensorimotor dysfunctions and to address the possible interplay of sex hormones with common risk factors associated with IBS.The scientific bibliography was searched using the following keywords:irritable bowel syndrome,sex,gender,ovarian hormone,estradiol,progesterone,testosterone,symptoms,pain,sensitivity,motility,permeability,stress,immune system,brain activity,spinal,supraspinal,imaging.Ovarian hormones variations along themenstrual cycle affect sensorimotor gastrointestinal function in both healthy and IBS populations.They can modulate pain processing by interacting with neuromodulator systems and the emotional system responsible for visceral pain perception.These hormones can also modulate the susceptibility to stress,which is a pivotal factor in IBS occurrence and symptom severity.For instance,estrogen-dependent hyper-responsiveness to stress can promote immune activation or impairments of gut barrier function.In conclusion,whereas it is important to keep in mind that ovarian hormones cannot be considered as a causal factor of IBS,they arguably modulate IBS onset and symptomatology.However,our understanding of the underlying mechanisms remains limited and studies assessing the link between IBS symptoms and ovarian hormone levels are needed to improve our knowledge of the disease evolution with regard to gender.Further studies assessing the role of male hormones are also needed to understand fully the role of sex hormones in IBS.Finally,investigation of brain-gut interactions is critical to decipher how stress,ovarian hormones,and female brain processing of pain can translate
基金supported by the National Natural Science Foundation of China(21672173,21372186)Research Fund for International Young Scientists from International(Regional)Cooperation and Exchange Program of NSFC(81650110529)+3 种基金Chongqing Special Foundation for Postdoctoral Research Proposal(Xm2016039,Xm2017185)Program for Overseas Young Talents from State Administration of Foreign Experts Affairs,China(WQ2017XNDX047)the Doctoral Fund of Southwest University(SWU111075)the Research Funds for the Central Universities(XDJK2017B015)
文摘A series of natural berberine-derived nitroimidazoles as novel antibacterial agents were designed, synthesized and characterized by nuclear magnetic resonance(NMR), infrared spectra(IR), and high resolution mass spectra(HRMS) spectra. The antimicrobial evaluation showed that some target molecules exhibited moderate to good inhibitory activities against the tested bacteria and fungi including clinical drug-resistant strains isolated from infected patients. Especially, 2-fluorobenzyl derivative8 f not only gave strong activity against drug-resistant E. coli with the minimal inhibitory concentration(MIC) value of0.003 m M, 33-fold more active than norfloxacin, but also exhibited low toxicity toward RAW 264.7 cells and less propensity to trigger resistance. The aqueous solubility and Clog P values of target compounds were investigated to elucidate the structureactivity relationships. Molecular docking and quantum chemical studies for compound 8 f rationally explained its antibacterial effect. The further exploration of antibacterial mechanism revealed that the highly active compound 8 f could effectively permeabilize E. coli cell membrane and intercalate into DNA isolated from resistant E. coli to form 8 f-DNA complex that might block DNA replication to exert the powerful bioactivities. Compound 8 f could also selectively address resistant E. coli from a mixture of various strains.
基金Supported by National Natural Science Funds of China,No.81503367the Budget Research Project of Shanghai Education Commission,No.2014YSN03 and No.2014YSN22
文摘AIM To investigate the capability of salvianolic acid B(Sal B) to protect hepatocytes from hydrogen peroxide(H_2O_2)/carbon tetrachloride(CCl_4)-induced lysosomal membrane permeabilization. METHODS Cell Counting Kit-8 assay was used to measure cell viability. Apoptosis and death were assayed through flow cytometry. Brd U incorporation was used to detect cell proliferation. Serum alanine aminotransferase activity and liver malondialdehyde(MDA) content were measured. Liver histopathological changes were evaluated using hematoxylin-eosin staining. Lysosomal membrane permeability was detected with Lyso Tracker Green-labeled probes and acridine orange staining. The levels of protein carbonyl content(PCC), cathepsins(Cat)B/D, and lysosome-associated membrane protein 1(LAMP1) were evaluated through western blotting. Cytosol Cat B activity analysis was performed with chemiluminescence detection. The m RNA level ofLAMP1 was evaluated through quantitative real-time polymerase chain reaction. RESULTS Results indicated that H_2O_2 induced cell injury/death. Sal B attenuated H_2O_2-induced cell apoptosis and death, restored the inhibition of proliferation, decreased the amount of PCC, and stabilized the lysosome membrane by increasing the LAMP1 protein level and antagonizing Cat B/D leakage into the cytosol. CCl_4 also triggered hepatocyte death. Furthermore, Sal B effectively rescued hepatocytes by increasing LAMP1 expression and by reducing lysosomal enzyme translocation to the cytosol.CONCLUSION Sal B protected mouse embryonic hepatocytes from H_2O_2/CCl_4-induced injury/death by stabilizing the lysosomal membrane.
基金supported by the National Natural Science Foundation of China(No.81772714).
文摘Objective:It has been reported that intrinsic apoptosis is associated with the progression of bladder cancer(BC).Recent evidence suggests that polyribonucleotide nucleotidyltransferase 1(PNPT1)is a pivotal mediator involved in RNA decay and cell apoptosis.However,the regulation and roles of PNPT1 in bladder cancer remain largely unclear.Methods:The upstream miRNA regulators were predicted by in silico analysis.The expression levels of PNPT1 were evaluated by real-time PCR,Western blotting,and immunohistochemistry(IHC),while miR-183-5p levels were evaluated by qPCR in BC cell lines and tissues.In vitro and in vivo assays were performed to investigate the function of miR-183-5p and PNPT1 in apoptotic RNA decay and the tumorigenic capability of bladder cancer cells.Results:PNPT1 expression was decreased in BC tissues and cell lines.Overexpression of PNPT1 significantly promoted cisplatin-induced intrinsic apoptosis of BC cells,whereas depletion of PNPT1 potently alleviated these effects.Moreover,oncogenic miR183-5p directly targeted the 3′UTR of PNPT1 and reversed the tumor suppressive role of PNPT1.Intriguingly,miR-183-5p modulated not only PNPT1 but also Bcl2 modifying factor(BMF)to inhibit the mitochondrial outer membrane permeabilization(MOMP)in BC cells.Conclusion:Our results provide new insight into the mechanisms underlying intrinsic apoptosis in BC,suggesting that the miR-183-5p-PNPT1 regulatory axis regulates the apoptosis of BC cells and might represent a potential therapeutic avenue for the treatment of BC.
文摘Many conventional anticancer drugs have an associated lack of safety by their toxicity. Relatively faster mutations in tumor cells pose a significant obstacle in treatment of cancer. Recently, “Mitocans” have emerged as a novel class of anticancer agents selectively targeting tumor cells and thus, are much less toxic than conventional anticancer chemotherapeutic agents. Mitocans are drugs that act directly on mitochondria within the cell, thus causing changes in energy metabolism of the cell. Amongst these mitocans, α-Tocopheryl succinate or vitamin E analogs are studied very well by researchers. This review discusses mitochondrial drug targeting strategies and a variety of novel mitochondrial drug targets of mitocans, such as electron transport chain, mitochondrial permeability transition, Bcl-2 family proteins and mitochondrial DNA. The purpose of this review is to focus on the various classes of mitocans, the mechanisms by which these drugs specifically act on tumor cells and their applications in cancer chemotherapeutics.
文摘The increased importance of the G. mellonella for wide range of scientific research and commercial sides will need to create a germplasm resource banking by cryopreservation. Impermeability is a fundamental limiting factor for the successful cryopreservation of arthropods embryos. The successful permeability of Drosophila embryo by using an embryo permeabilization solvent (EPS) solution encouraged this trial on G. mellonella embryos (stage of 24 hours Post-oviposition (h PO)). Permeability assessment with Rhodamine B and crystal violet dyes showed that G. mellonella embryos can be permeabilized by EPS of D-limonene that has 3 mol ethoxylated alcohol. The permeabilization for 30 sec exposure time was resulted 61.5% ± 5.8% survival rate, 31.7% ± 3.1% uptakes dyes and 40.5% ± 0.3% was the survival rate post loading in 12% Ethylene glycol (EG). The low viability after immersion in liquid nitrogen (LN) (0.6% ± 0.08%) is due to the dual toxicity of EPS and cryoprotectant (CPA) solutions. However, fluorescence images showed sufficient permeability that confirms the possibility to increase the permeability of G. mellonella embryos with EPS solution, and to have the opportunity to improve the viability after LN by improving procedures of loading and dehydration with various CPAs and exposure times, which decrease the toxicity effect.
文摘We reported previously that chymotrypsin B is cached in the lysosomes of rat hepatocytes and mediates apoptosis induced by TNF-alpha (1) and H2O2. However, the mechanism
