Muscle atrophy can be induced by high doses or prolonged use of glucocorticoids.Kaempferol(Kae)is a naturally occurring flavonoid with a variety of biological activities and the effect of Kae on dexamethasone(Dex)indu...Muscle atrophy can be induced by high doses or prolonged use of glucocorticoids.Kaempferol(Kae)is a naturally occurring flavonoid with a variety of biological activities and the effect of Kae on dexamethasone(Dex)induced muscle atrophy in animals has not been elucidated.To explore this issue,the present experiments used a computationally assisted drug design scheme combining network pharmacology,molecular docking and in vivo experiments to investigate the mechanism of Kae against muscle atrophy.Network pharmacological analyses revealed 275 potential targets for Kae and 12294 potential targets for muscle atrophy,with a total of 228 crosstargets for Kae and muscle atrophy.GO and KEGG analyses were performed based on the protein-protein interaction(PPI)network of muscle atrophy and Kae component targets.The GO results showed that the biological processes were mainly related to the metabolic process of reactive oxygen species,and the response to oxidative stress;the cellular components were mainly focused on membrane microdomains,and membrane regions;the molecular functions mainly worked on phosphatase binding;and the KEGG pathway enrichment analyses identified the pathways of interaction between Kae and muscle atrophy.Finally,as verified by in vivo experiments,Kae may reduce the onset of muscle atrophy by activating the PI3K/AKT/m TOR/signalling pathway,inhibiting Foxo1/Foxo3 activity,and inhibiting downstream production of the ubiquitination 3 ligases Atrogin1 and Mu RF1;Kae also promotes the expression of NRF2/HO-1/KEAP1 signalling pathway,enhances muscle antioxidant capacity,inhibits the release of COX-2 and TNF-αinflammatory factors,and reduces the damage caused by oxidative stress and inflammatory factors to muscles.Therefore,there may be a synergistic effect of PI3K/AKT/m TOR and NRF2/HO-1/KEAP1 in Kae working together to prevent muscle atrophy.The binding energy and stability of Kae to potential targets were examined by molecular docking and molecular dynamics simulations,implying that Kae could be used for the prevention and treatment of muscle atrophy in patients.展开更多
Increased nitrogen （N） deposition will often lead to a decline in species richness in grassland ecosystems but the shifts in functional groups and plant traits are still poorly understood in China. A field experimen...Increased nitrogen （N） deposition will often lead to a decline in species richness in grassland ecosystems but the shifts in functional groups and plant traits are still poorly understood in China. A field experiment was conducted at Duolun, Inner Mongolia, China, to investigate the effects of N addition on a temperate steppe ecosystem. Six N levels （0, 3, 6, 12, 24, and 48 g N/（m2-a）） were added as three applications per year from 2005 to 2010. Enhanced N deposition, even as little as 3 g N/（m2.a） above ambient N deposition （1.2 g N/（m2.a））, led to a decline in species richness of the whole community. Increasing N addition can significantly stimulate aboveground biomass of perennial bunchgrasses （PB） but decrease perennial forbs （PF）, and induce a slight change in the biomass of shrubs and semi-shrubs （SS）. The biomass of annuals （AS） and perennial rhizome grasses （PR） accounts for only a small part of the total biomass. Species richness of PF decreased significantly with increasing N addition rate but there was a little change in the other functional groups. PB, as the dominant functional group, has a relatively higher height than others. Differences in the response of each functional group to N addition have site-specific and species-specific characteristics. We initially infer that N enrichment stimulated the growth of PB, which further suppressed the growth of other functional groups.展开更多
The TP53, a transcriptional regulator and tumor suppressor, is functionally important in spermatogenesis. MDM2 is a key regulator of the p53 pathway and modulates p53 activity. Both proteins have been functionally lin...The TP53, a transcriptional regulator and tumor suppressor, is functionally important in spermatogenesis. MDM2 is a key regulator of the p53 pathway and modulates p53 activity. Both proteins have been functionally linked to germ cell apoptosis, which may affect human infertility, but very little is known on how common polymorphisms in these genes may influence germ cell apoptosis and the risk of male infertility. Thus, this study was designed to test whether three previously described polymorphisms 72Arg〉Pro （rs1042522） and the Ex2＋ 19C〉T （rs2287498） in TP53, and the 5＇ untranslated region （5＇ UTR） 309T〉G （rs937283） in MDM2, are associated with idiopathic male infertility in a Chinese population. The three polymorphisms were genotyped using OpenArray assay in a hospital-based case-control study, including 580 infertile patients and 580 fertile controls. Our analyses revealed that TP53 Ex2-1-19C〉T and MDM2 309T〉G polymorphisms are associated with male infertility. Furthermore, we detected a nearly statistically significant additive interaction between TP53 rs2287498 and MDM2 rs937283 for the development of male infertility （Pinteraction--O-055）- In summary, this study found preliminary evidence, demonstrating that genetic variants in genes of the TP53 pathway are risk factors for male infertility.展开更多
Follicle-stimulating hormone receptor （FSHR）, which is expressed only on Sertoli cells and plays a key role in spermatogenesis, has been paid attention for its potential in male contraception vaccine research and de...Follicle-stimulating hormone receptor （FSHR）, which is expressed only on Sertoli cells and plays a key role in spermatogenesis, has been paid attention for its potential in male contraception vaccine research and development. This study introduces a method for the preparation and purification of human FSHR 57-amino acid protein （FSHR-57aa） as well as determination of its immunogenicity and antifertility effect. A recombinant pET-28a（＋）-FSHR-57aa plasmid was constructed and expressed in Escherichia coil strain BL21 StarTM （DE3） and the FSHR-57aa protein was separated and collected by cutting the gel and recovering activity by efficient refolding dialysis. The protein was identified by Western blot and high-performance liquid chromatography analysis with a band of nearly 7 kDa and a purity of 97.4%. Male monkeys were immunized with rhFSHR-57aa protein and a gradual rising of specific serum IgG antibody was found which reached a plateau on day 112 （16 weeks） after the first immunization. After mating of one male with three female monkeys, the pregnancy rate of those mated with males immunized against FSHR-57aa was significantly decreased while the serum hormone levels of testosterone and estradiol were not disturbed in the control or the FSHR-57aa groups. By evaluating pathological changes in testicular histology, we found that the blood-testis barrier remained intact, in spite of some small damage to Sertoli cells. In conclusion, our study demonstrates that the rhFSHR-57aa protein might be a feasible male contraceptive which could affect sperm production without disturbing hormone levels.展开更多
基金funded by Yunnan Youth Top-notch Talent Support Program(YNWR-QNBJ2018-173)Agricultural Joint project of Yunnan Provincial S&T Programs(202301BD070001-195)+2 种基金S&T project of Yunnan provincial finance(K212020001-01)supported by Yunnan Province Education Department’s Engineering Research Center of Eco-friendly Products from Yunnan Characteristic Edible FungiYunnan Province Yongsheng County Farmer Academician Technology service station.
文摘Muscle atrophy can be induced by high doses or prolonged use of glucocorticoids.Kaempferol(Kae)is a naturally occurring flavonoid with a variety of biological activities and the effect of Kae on dexamethasone(Dex)induced muscle atrophy in animals has not been elucidated.To explore this issue,the present experiments used a computationally assisted drug design scheme combining network pharmacology,molecular docking and in vivo experiments to investigate the mechanism of Kae against muscle atrophy.Network pharmacological analyses revealed 275 potential targets for Kae and 12294 potential targets for muscle atrophy,with a total of 228 crosstargets for Kae and muscle atrophy.GO and KEGG analyses were performed based on the protein-protein interaction(PPI)network of muscle atrophy and Kae component targets.The GO results showed that the biological processes were mainly related to the metabolic process of reactive oxygen species,and the response to oxidative stress;the cellular components were mainly focused on membrane microdomains,and membrane regions;the molecular functions mainly worked on phosphatase binding;and the KEGG pathway enrichment analyses identified the pathways of interaction between Kae and muscle atrophy.Finally,as verified by in vivo experiments,Kae may reduce the onset of muscle atrophy by activating the PI3K/AKT/m TOR/signalling pathway,inhibiting Foxo1/Foxo3 activity,and inhibiting downstream production of the ubiquitination 3 ligases Atrogin1 and Mu RF1;Kae also promotes the expression of NRF2/HO-1/KEAP1 signalling pathway,enhances muscle antioxidant capacity,inhibits the release of COX-2 and TNF-αinflammatory factors,and reduces the damage caused by oxidative stress and inflammatory factors to muscles.Therefore,there may be a synergistic effect of PI3K/AKT/m TOR and NRF2/HO-1/KEAP1 in Kae working together to prevent muscle atrophy.The binding energy and stability of Kae to potential targets were examined by molecular docking and molecular dynamics simulations,implying that Kae could be used for the prevention and treatment of muscle atrophy in patients.
基金supported by the One Hundred Person Project of Chinese Academy of Sciencesthe National Natural Science Foundation of China (40771188,41071151)+1 种基金the Innovative Group Grants from NSFC (30821003)the Sino-German project (DFG Research Training Group,GK1070)
文摘Increased nitrogen （N） deposition will often lead to a decline in species richness in grassland ecosystems but the shifts in functional groups and plant traits are still poorly understood in China. A field experiment was conducted at Duolun, Inner Mongolia, China, to investigate the effects of N addition on a temperate steppe ecosystem. Six N levels （0, 3, 6, 12, 24, and 48 g N/（m2-a）） were added as three applications per year from 2005 to 2010. Enhanced N deposition, even as little as 3 g N/（m2.a） above ambient N deposition （1.2 g N/（m2.a））, led to a decline in species richness of the whole community. Increasing N addition can significantly stimulate aboveground biomass of perennial bunchgrasses （PB） but decrease perennial forbs （PF）, and induce a slight change in the biomass of shrubs and semi-shrubs （SS）. The biomass of annuals （AS） and perennial rhizome grasses （PR） accounts for only a small part of the total biomass. Species richness of PF decreased significantly with increasing N addition rate but there was a little change in the other functional groups. PB, as the dominant functional group, has a relatively higher height than others. Differences in the response of each functional group to N addition have site-specific and species-specific characteristics. We initially infer that N enrichment stimulated the growth of PB, which further suppressed the growth of other functional groups.
文摘The TP53, a transcriptional regulator and tumor suppressor, is functionally important in spermatogenesis. MDM2 is a key regulator of the p53 pathway and modulates p53 activity. Both proteins have been functionally linked to germ cell apoptosis, which may affect human infertility, but very little is known on how common polymorphisms in these genes may influence germ cell apoptosis and the risk of male infertility. Thus, this study was designed to test whether three previously described polymorphisms 72Arg〉Pro （rs1042522） and the Ex2＋ 19C〉T （rs2287498） in TP53, and the 5＇ untranslated region （5＇ UTR） 309T〉G （rs937283） in MDM2, are associated with idiopathic male infertility in a Chinese population. The three polymorphisms were genotyped using OpenArray assay in a hospital-based case-control study, including 580 infertile patients and 580 fertile controls. Our analyses revealed that TP53 Ex2-1-19C〉T and MDM2 309T〉G polymorphisms are associated with male infertility. Furthermore, we detected a nearly statistically significant additive interaction between TP53 rs2287498 and MDM2 rs937283 for the development of male infertility （Pinteraction--O-055）- In summary, this study found preliminary evidence, demonstrating that genetic variants in genes of the TP53 pathway are risk factors for male infertility.
基金This study was supported by the National Key Technologies R and D Program （No. 2012BAI31B07 and No. 2006BAI03B12）, the National Science Foundationof China （No. 81172694）. This project was also funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.
文摘Follicle-stimulating hormone receptor （FSHR）, which is expressed only on Sertoli cells and plays a key role in spermatogenesis, has been paid attention for its potential in male contraception vaccine research and development. This study introduces a method for the preparation and purification of human FSHR 57-amino acid protein （FSHR-57aa） as well as determination of its immunogenicity and antifertility effect. A recombinant pET-28a（＋）-FSHR-57aa plasmid was constructed and expressed in Escherichia coil strain BL21 StarTM （DE3） and the FSHR-57aa protein was separated and collected by cutting the gel and recovering activity by efficient refolding dialysis. The protein was identified by Western blot and high-performance liquid chromatography analysis with a band of nearly 7 kDa and a purity of 97.4%. Male monkeys were immunized with rhFSHR-57aa protein and a gradual rising of specific serum IgG antibody was found which reached a plateau on day 112 （16 weeks） after the first immunization. After mating of one male with three female monkeys, the pregnancy rate of those mated with males immunized against FSHR-57aa was significantly decreased while the serum hormone levels of testosterone and estradiol were not disturbed in the control or the FSHR-57aa groups. By evaluating pathological changes in testicular histology, we found that the blood-testis barrier remained intact, in spite of some small damage to Sertoli cells. In conclusion, our study demonstrates that the rhFSHR-57aa protein might be a feasible male contraceptive which could affect sperm production without disturbing hormone levels.
