Background:SMAD family proteins(SMADs)are crucial transcription factors downstream of transforming growth factor beta(TGF-ß)/SMAD signaling pathways that have been reported to play a pivotal role in mammalian rep...Background:SMAD family proteins(SMADs)are crucial transcription factors downstream of transforming growth factor beta(TGF-ß)/SMAD signaling pathways that have been reported to play a pivotal role in mammalian reproduction.However,the role of SMAD family member 8(SMAD8,also known as SMAD9),a member of the SMAD family,in mammalian reproduction remains unclear.Methods:We employed RNA interference techniques to knock down Smad8 expression in mouse granulosa cells(GCs)to investigate the effects of Smad8 on GC growth and steroidogenesis.Results:Our findings revealed a significant decrease in the proliferative capacity and a substantial increase in the apoptosis rate of GCs after transfection with Smad8-siRNA for 48 h.Subsequent hormone assays demonstrated a significant decrease in estradiol(E2)levels,whereas progesterone(P4)remained unchanged.Further mechanistic analysis showed that the mRNA expression of proliferating cell nuclear antigen(Pcna),Cyclin D2,cell cycle-dependent kinase 4(Cdk4),B-cell lymphoma-2(Bcl-2),estrogen receptor(Er),luteinizing hormone receptor(Lhr)and cytochrome P450 family 19 subfamily A member 1(Cyp19a1)significantly decreased.Conversely,the mRNA of cysteine aspartate proteinase 3(Caspase 3)significantly increased,wheras Bcl2-associated X(Bax),folliclestimulating hormone receptor(Fshr)and cytochrome P450 family 11 subfamily A member 1(Cyp11a1)remained unchanged compared to the controls.Conclusion:This study indicates that Smad8 knockdown inhibits cell proliferation,promotes apoptosis,reduces Er and Lhr transcription,and decreases E2 production in mouse GCs.These findings suggest that Smad8 may serve as a novel genetic marker for mammalian reproduction.展开更多
Abstract Spinal cord injury （SCI） remains an unsolved human health challenge. To alleviate the impairments of SCI, we studied the therapeutic effect of nimodipine （an L-type Ca^2＋ channel antagonist） on functiona...Abstract Spinal cord injury （SCI） remains an unsolved human health challenge. To alleviate the impairments of SCI, we studied the therapeutic effect of nimodipine （an L-type Ca^2＋ channel antagonist） on functional recovery from SCI using Nystrom＇s method in a mouse model. Eighty-four mice were divided into three groups： control group in which only vertebral plates were cut off without causing any spinal injuries; SCI; and SCI with nimodipine treatment. We assessed the histopathology, apoptosis detection, cell cycle, mitochondrial transmembrane potential, bcl-2/bax and caspase-3 levels of tissue 8 h, 1 d, 3 d and 4 d after trauma to evaluate rehabilitation. Behavioral performances were also assessed before and after nimodipine treatment. Results from inclined plane tests, motor score assessment and histological observations indicated that mice in the nimodipine-treated group rehabilitated better than those in the SCI group. The ratio of apoptosis, caspase-3 and bax expression in the nimodip- ine-treated group were significantly lower than those in the SCI group. The mitochondrial membrane potential and bcl-2 expression were up-regulated in the nimodipine-treated group. Taken together, our results indicate that the inhibition of calcium flux by nimodipine could reduce apoptosis processes and tissue damage through a mitochondrial pathway after spinal cord trauma [Current Zoology 57 （3）： 340-349, 2011].展开更多
We demonstrated the simple and effective production of transgenic chickens, in which the enhanced green fluorescence protein （EGFP） was expressed by using third-generation self-inactive HIV-based lentiviral vectors....We demonstrated the simple and effective production of transgenic chickens, in which the enhanced green fluorescence protein （EGFP） was expressed by using third-generation self-inactive HIV-based lentiviral vectors. In our experiments, lentiviruses were injected into 204 fertilized eggs, from which 30 （15%） chickens were hatched. The exogenous gene was detected in the genomes of 16 out of 30 （53%） chickens. The green fluorescence signal was observed directly in various body parts, and was particularly significant in the testes. The transgenes were also found in the offspring of these chickens. The results indicate that HIV-based lentiviral vectors can be used to generate transgenic birds economically and effectively [ Current Zoology 55 （5）： 383 - 387,2009].展开更多
Spinal cord injury(SCI)remains an intractable clinical challenge of neurosurgery,it can be divided into two stages:uncontrollable primary injury induced by mechanical damage and controllable secondary injury regulated...Spinal cord injury(SCI)remains an intractable clinical challenge of neurosurgery,it can be divided into two stages:uncontrollable primary injury induced by mechanical damage and controllable secondary injury regulated by continuous cell death.The apoptosis was the one of most important events in secondary injury,previous studies revealed that excessive endoplasmic reticulum(ER)stress breaks down the homeostasis and triggers apoptosis in the spinal cord.To deter or alleviate the secondary jury,we screen one of fat-soluble compounds,salubrinal,which was an inhibitor of eIF2αdephosphorylation can repair SCI by inhibiting ER stress in mice after SCI.Administration of salubrinal effectively represses apoptosis,protects neuronal cell,and promotes the restoration of locomotor function in mice SCI models.Furthermore,the level of phosphorylated eIF2αwas raised in the presence of salubrinal,but the protein expression of ATF4 and CHOP was downregulated.Unexpectedly,transcriptional expression of CHOPregulated pro-apoptotic genes was decreased.These data suggest salubrinal suppress ER stress by targeting eIF2α/ATF4 pathways and reduces cell death after SCI.It is suggested that the mitigation of secondary lesion by inhibiting ER stress induced apoptosis in the early phase of SCI is promising treatment strategy.展开更多
Therapeutic nanoparticles are designed to enhance efficacy,real-time monitoring,targeting accuracy,biocompatibility,biodegradability,safety,and the synergy of diagnosis and treatment of diseases by leveraging the uniq...Therapeutic nanoparticles are designed to enhance efficacy,real-time monitoring,targeting accuracy,biocompatibility,biodegradability,safety,and the synergy of diagnosis and treatment of diseases by leveraging the unique physicochemical and biological properties of well-developed bio-nanomaterials.Recently,bio-inspired metal nanoclusters(NCs)consisting of several to roughly dozens of atoms(<2 nm)have attracted increasing research interest,owing to their ultrafine size,tunable fluorescent capability,good biocompatibility,variable metallic composition,and extensive surface bio-functionalization.Hybrid coreeshell nanostructures that effectively incorporate unique fluorescent inorganic moieties with various biomolecules,such as proteins(enzymes,antigens,and antibodies),DNA,and specific cells,create fluorescently visualized molecular nanoparticle.The resultant nanoparticles possess combinatorial properties and synergistic efficacy,such as simplicity,active bio-responsiveness,improved applicability,and low cost,for combination therapy,such as accurate targeting,bioimaging,and enhanced therapeutic and biocatalytic effects.In contrast to larger nanoparticles,bio-inspired metal NCs allow rapid renal clearance and better pharmacokinetics in biological systems.Notably,advances in nanoscience,interfacial chemistry,and biotechnologies have further spurred researchers to explore bio-inspired metal NCs for therapeutic purposes.The current review presents a comprehensive and timely overview of various metal NCs for various therapeutic applications,with a special emphasis on the design rationale behind the use of biomolecules/cells as the main scaffolds.In the different hybrid platform,we summarize the current challenges and emerging perspectives,which are expected to offer in-depth insight into the rational design of bio-inspired metal NCs for personalized treatment and clinical translation.展开更多
基金supported by the High-Level Talent Research Start-Up Funds of West Anhui University(No.WGKQ2021031)Key Project of Natural Science Foundation of Anhui Province of China(No.2108085QC136)+2 种基金Key Project of Quality Engineering in Higher Education Institutions of Anhui Province(No.2020jyxm2128)National College Student Innovation and Entrepreneurship Training Program(No.202110370093)Innovation and Entrepreneurship Training Program for College Students of Anhui Province(No.S202010376114).
文摘Background:SMAD family proteins(SMADs)are crucial transcription factors downstream of transforming growth factor beta(TGF-ß)/SMAD signaling pathways that have been reported to play a pivotal role in mammalian reproduction.However,the role of SMAD family member 8(SMAD8,also known as SMAD9),a member of the SMAD family,in mammalian reproduction remains unclear.Methods:We employed RNA interference techniques to knock down Smad8 expression in mouse granulosa cells(GCs)to investigate the effects of Smad8 on GC growth and steroidogenesis.Results:Our findings revealed a significant decrease in the proliferative capacity and a substantial increase in the apoptosis rate of GCs after transfection with Smad8-siRNA for 48 h.Subsequent hormone assays demonstrated a significant decrease in estradiol(E2)levels,whereas progesterone(P4)remained unchanged.Further mechanistic analysis showed that the mRNA expression of proliferating cell nuclear antigen(Pcna),Cyclin D2,cell cycle-dependent kinase 4(Cdk4),B-cell lymphoma-2(Bcl-2),estrogen receptor(Er),luteinizing hormone receptor(Lhr)and cytochrome P450 family 19 subfamily A member 1(Cyp19a1)significantly decreased.Conversely,the mRNA of cysteine aspartate proteinase 3(Caspase 3)significantly increased,wheras Bcl2-associated X(Bax),folliclestimulating hormone receptor(Fshr)and cytochrome P450 family 11 subfamily A member 1(Cyp11a1)remained unchanged compared to the controls.Conclusion:This study indicates that Smad8 knockdown inhibits cell proliferation,promotes apoptosis,reduces Er and Lhr transcription,and decreases E2 production in mouse GCs.These findings suggest that Smad8 may serve as a novel genetic marker for mammalian reproduction.
文摘Abstract Spinal cord injury （SCI） remains an unsolved human health challenge. To alleviate the impairments of SCI, we studied the therapeutic effect of nimodipine （an L-type Ca^2＋ channel antagonist） on functional recovery from SCI using Nystrom＇s method in a mouse model. Eighty-four mice were divided into three groups： control group in which only vertebral plates were cut off without causing any spinal injuries; SCI; and SCI with nimodipine treatment. We assessed the histopathology, apoptosis detection, cell cycle, mitochondrial transmembrane potential, bcl-2/bax and caspase-3 levels of tissue 8 h, 1 d, 3 d and 4 d after trauma to evaluate rehabilitation. Behavioral performances were also assessed before and after nimodipine treatment. Results from inclined plane tests, motor score assessment and histological observations indicated that mice in the nimodipine-treated group rehabilitated better than those in the SCI group. The ratio of apoptosis, caspase-3 and bax expression in the nimodip- ine-treated group were significantly lower than those in the SCI group. The mitochondrial membrane potential and bcl-2 expression were up-regulated in the nimodipine-treated group. Taken together, our results indicate that the inhibition of calcium flux by nimodipine could reduce apoptosis processes and tissue damage through a mitochondrial pathway after spinal cord trauma [Current Zoology 57 （3）： 340-349, 2011].
基金supported by National High Technology Research and Development Program of China(863 Key Program,No.2007AA100504)Anhui Natural Science Foundation(No.050410201)
文摘We demonstrated the simple and effective production of transgenic chickens, in which the enhanced green fluorescence protein （EGFP） was expressed by using third-generation self-inactive HIV-based lentiviral vectors. In our experiments, lentiviruses were injected into 204 fertilized eggs, from which 30 （15%） chickens were hatched. The exogenous gene was detected in the genomes of 16 out of 30 （53%） chickens. The green fluorescence signal was observed directly in various body parts, and was particularly significant in the testes. The transgenes were also found in the offspring of these chickens. The results indicate that HIV-based lentiviral vectors can be used to generate transgenic birds economically and effectively [ Current Zoology 55 （5）： 383 - 387,2009].
基金This study was supported by Anhui Natural Science Foundation(1908085MC83)the National Natural Science Foundation of China(31970413)Wuhu Science and Technology Bureau Project(2019cg19).
文摘Spinal cord injury(SCI)remains an intractable clinical challenge of neurosurgery,it can be divided into two stages:uncontrollable primary injury induced by mechanical damage and controllable secondary injury regulated by continuous cell death.The apoptosis was the one of most important events in secondary injury,previous studies revealed that excessive endoplasmic reticulum(ER)stress breaks down the homeostasis and triggers apoptosis in the spinal cord.To deter or alleviate the secondary jury,we screen one of fat-soluble compounds,salubrinal,which was an inhibitor of eIF2αdephosphorylation can repair SCI by inhibiting ER stress in mice after SCI.Administration of salubrinal effectively represses apoptosis,protects neuronal cell,and promotes the restoration of locomotor function in mice SCI models.Furthermore,the level of phosphorylated eIF2αwas raised in the presence of salubrinal,but the protein expression of ATF4 and CHOP was downregulated.Unexpectedly,transcriptional expression of CHOPregulated pro-apoptotic genes was decreased.These data suggest salubrinal suppress ER stress by targeting eIF2α/ATF4 pathways and reduces cell death after SCI.It is suggested that the mitigation of secondary lesion by inhibiting ER stress induced apoptosis in the early phase of SCI is promising treatment strategy.
基金support from National Natural Science Foundation of China(Grant No.11802066)Science and Technology Innovation Committee of Shenzhen(JCYJ20170818091601315,China)support from the China Postdoctoral Science Foundation(2019M01294501)。
文摘Therapeutic nanoparticles are designed to enhance efficacy,real-time monitoring,targeting accuracy,biocompatibility,biodegradability,safety,and the synergy of diagnosis and treatment of diseases by leveraging the unique physicochemical and biological properties of well-developed bio-nanomaterials.Recently,bio-inspired metal nanoclusters(NCs)consisting of several to roughly dozens of atoms(<2 nm)have attracted increasing research interest,owing to their ultrafine size,tunable fluorescent capability,good biocompatibility,variable metallic composition,and extensive surface bio-functionalization.Hybrid coreeshell nanostructures that effectively incorporate unique fluorescent inorganic moieties with various biomolecules,such as proteins(enzymes,antigens,and antibodies),DNA,and specific cells,create fluorescently visualized molecular nanoparticle.The resultant nanoparticles possess combinatorial properties and synergistic efficacy,such as simplicity,active bio-responsiveness,improved applicability,and low cost,for combination therapy,such as accurate targeting,bioimaging,and enhanced therapeutic and biocatalytic effects.In contrast to larger nanoparticles,bio-inspired metal NCs allow rapid renal clearance and better pharmacokinetics in biological systems.Notably,advances in nanoscience,interfacial chemistry,and biotechnologies have further spurred researchers to explore bio-inspired metal NCs for therapeutic purposes.The current review presents a comprehensive and timely overview of various metal NCs for various therapeutic applications,with a special emphasis on the design rationale behind the use of biomolecules/cells as the main scaffolds.In the different hybrid platform,we summarize the current challenges and emerging perspectives,which are expected to offer in-depth insight into the rational design of bio-inspired metal NCs for personalized treatment and clinical translation.
