Introduction of neurogenesis： Neurogenesis is a process charac- terized by the production and differentiation of new neurons from neural stem cells （Emsley et al., 2005）. This was previously thought to occur in pre...Introduction of neurogenesis： Neurogenesis is a process charac- terized by the production and differentiation of new neurons from neural stem cells （Emsley et al., 2005）. This was previously thought to occur in prenatal and early postnatal development only; how- ever, several studies have shown that it occurs continuously in our adult brains as well, mainly in the lateral ventricles of the brain, the lining of the subventricular zone （SVZ）, and the subgranular zone （SGZ） of the dentate gyrus （part of the hippocampal complex）. Neurogenesis may also be induced in the adult brain by injury or degeneration of the central nervous system （CNS）. In this instance, new neurons have been found in other parts of the brain, such as in the neocortex, amygdala, substantia nigra and tegmentum of the midrain, the brain stem and spinal cord （Wang and Jin, 2014）. There are numerous steps involved in differentiating neural stem cells into fully-grown neurons, starting with stem cell proliferation, then migration and survival, followed by commitment to neuronal lineage, and lastly the assimilation of the new neurons into existing brain circuits, ranging from up in the neocortex to down in the spinal cord. Neurogenesis is a dynamic process that is modulated by several factors, both intrinsic and extrinsic, such as growth and transcriptional factors, cell surface receptors, signal transduction molecules, and cytokine or chemokines. In adult brains, physio- logical as well as pathological conditions can affect neurogenesis. Neural stem cell proliferation and neuronal differentiation can be inhibited by infection or invoked inflammation. The interruption of neurogenesis in adult brains leads to hippocampus-dependent learning and behavior impairment （Yan et al., 2007）.展开更多
Background： Inflammation is often linked with the progress and poor outcome of lung cancer. The understanding of the relationship between tumor-associated macrophages （TAMs） and lung cancer cells involves in the un...Background： Inflammation is often linked with the progress and poor outcome of lung cancer. The understanding of the relationship between tumor-associated macrophages （TAMs） and lung cancer cells involves in the underlying mechanism of inflammatory cytokine production. Toll-like receptors （TLRs） are engaged in promoting the production of pro-inflammatory cytokines and play an important role in tumor immunology. Methods： To investigate the mechanisms by which TAMs influence the production of pro-inflammatory cytoldnes in lung cancer cells, we established an in vitro coculture system using TAMs and human non- small cell lung cancer （NSCLC） cell line SPC-A1. Levels of interleukin （IL）-113, IL-6 and IL-8 in SPC-A1 were evaluated by RT-PCR and cytometric bead array assay after being cocultured with TAMs. Expression changes of TLRs and TLRs signaling pathway proteins in SPC-Al were further confirmed by RT-PCR and western blot. The level changes of IL-1β, IL-6 and IL-8 in SPC-Al were also detected after the stimulation of TLRs agonists. Results： We found that the phenotype markers of TAMs were highly expressed after stimulating human monocyte cell line THP-1 by phorbol-12-myristate-β-acetate （PMA）. Higher mRNA and supernate secretion levels of IL-1β, IL-6 and IL-8 were detected in SPC-A1 after being eocultured with TAMs. We also found that TLR1, TLR6 and TLR7 were up-regulated in SPC-A1 in the coculture system with TAMs. Meanwhile, TLRs signaling pathway proteins were also significantly activated. Moreover, pre-treatment with agonist ligands for TLR1, TLR6 and TLR7 could dramatically promote inductions of IL-1β, IL-6 and IL-8. Conclusions： These findings demonstrated that TAMs may enhance IL-1β, IL-6 and IL-8 expressions via TLRs signaling pathway. We conclude that TAMs contribute to maintain the inflammation microenvironment and ultimately promote the development and progression of lung cancer.展开更多
Pregnancy is a unique immunologic and microbial condition that requires an adequate level of awareness to provide a fast and protective response against pathogens as well as to maintain a state of tolerance to paterna...Pregnancy is a unique immunologic and microbial condition that requires an adequate level of awareness to provide a fast and protective response against pathogens as well as to maintain a state of tolerance to paternal antigens.Dysregulation of inflammatory pathways in the placenta triggered by pathogens is one of the main factors responsible for pregnancy complications.Type I IFNs are key molecules modulating immune responses at the level of the placenta and are crucial for protection of the pregnancy via their antiviral and immune modulatory properties.In this study,we elucidate the mechanisms controlling the basal expression of IFNβand its negative feedback.Using in vitro and in vivo animal models,we found that TLR signaling maintains basal IFNβlevels through the TLR4-MyD88-independent TBK/IRF3 signaling pathway.We describe the role of the TAM receptor Axl in the regulation of IFNβfunction in human and mouse trophoblast cells.The absence of TAM receptors in vivo is associated with fetal demise due to dysregulation of IFNβexpression and its pro-apoptotic downstream effectors.Collectively,our data describe a feedback signaling pathway controlling the expression and function of IFNβin the trophoblast that is essential for an effective response during viral and microbial infections.展开更多
目的:观察柴胡疏肝散联合他莫昔芬对大鼠乳腺增生的干预作用。方法:50只随机大鼠分为对照组,模型组,柴胡疏肝散(6.3 g·kg^(-1))组,他莫昔芬(1.67 mg·kg^(-1))组,柴胡疏肝散+他莫昔芬组。采用夹尾激怒法制备大鼠乳腺增生模型,...目的:观察柴胡疏肝散联合他莫昔芬对大鼠乳腺增生的干预作用。方法:50只随机大鼠分为对照组,模型组,柴胡疏肝散(6.3 g·kg^(-1))组,他莫昔芬(1.67 mg·kg^(-1))组,柴胡疏肝散+他莫昔芬组。采用夹尾激怒法制备大鼠乳腺增生模型,灌胃给药30d。酶联免疫法测定血清雌二醇,孕酮和催乳素,免疫组化法检测乳腺组织中雌激素受体及孕激素受体的表达。结果:与模型组比较,柴胡疏肝散联合他莫昔芬组大鼠血清中催乳素[(837.223±34.163)μg·L-1vs(346.215±43.114)μg·L-1,P<0.05]、雌二醇[(15.713±1.231)ng·L-1vs(4.973±0.278)ng·L-1,P<0.05)]的含量有效降低,孕酮[(0.423±0.031)μg·L-1vs(1.235±0.096)μg·L-1,P<0.05)]的含量提高;乳腺组织中雌激素受体表达显著被抑制(7.462±0.534 vs 4.889±0.343,P<0.05),孕激素受体的表达显著增强(1.212±0.53 vs 2.232±0.415,P<0.05)。结论:柴胡疏肝散联合他莫昔芬对大鼠乳腺增生有明显干预作用。展开更多
文摘Introduction of neurogenesis： Neurogenesis is a process charac- terized by the production and differentiation of new neurons from neural stem cells （Emsley et al., 2005）. This was previously thought to occur in prenatal and early postnatal development only; how- ever, several studies have shown that it occurs continuously in our adult brains as well, mainly in the lateral ventricles of the brain, the lining of the subventricular zone （SVZ）, and the subgranular zone （SGZ） of the dentate gyrus （part of the hippocampal complex）. Neurogenesis may also be induced in the adult brain by injury or degeneration of the central nervous system （CNS）. In this instance, new neurons have been found in other parts of the brain, such as in the neocortex, amygdala, substantia nigra and tegmentum of the midrain, the brain stem and spinal cord （Wang and Jin, 2014）. There are numerous steps involved in differentiating neural stem cells into fully-grown neurons, starting with stem cell proliferation, then migration and survival, followed by commitment to neuronal lineage, and lastly the assimilation of the new neurons into existing brain circuits, ranging from up in the neocortex to down in the spinal cord. Neurogenesis is a dynamic process that is modulated by several factors, both intrinsic and extrinsic, such as growth and transcriptional factors, cell surface receptors, signal transduction molecules, and cytokine or chemokines. In adult brains, physio- logical as well as pathological conditions can affect neurogenesis. Neural stem cell proliferation and neuronal differentiation can be inhibited by infection or invoked inflammation. The interruption of neurogenesis in adult brains leads to hippocampus-dependent learning and behavior impairment （Yan et al., 2007）.
基金the technical support from National Key Clinical Department of Laboratory Medicine of Jiangsu Province Hospitalsupported by National Natural Science Foundation of China(No. 81272324,81371894)+1 种基金Key Laboratory for Medicine of Jiangsu Province of China(No.XK201114)project funded by the Priority Academic Program Development ofJiangsu Higher Education Institutions
文摘Background： Inflammation is often linked with the progress and poor outcome of lung cancer. The understanding of the relationship between tumor-associated macrophages （TAMs） and lung cancer cells involves in the underlying mechanism of inflammatory cytokine production. Toll-like receptors （TLRs） are engaged in promoting the production of pro-inflammatory cytokines and play an important role in tumor immunology. Methods： To investigate the mechanisms by which TAMs influence the production of pro-inflammatory cytoldnes in lung cancer cells, we established an in vitro coculture system using TAMs and human non- small cell lung cancer （NSCLC） cell line SPC-A1. Levels of interleukin （IL）-113, IL-6 and IL-8 in SPC-A1 were evaluated by RT-PCR and cytometric bead array assay after being cocultured with TAMs. Expression changes of TLRs and TLRs signaling pathway proteins in SPC-Al were further confirmed by RT-PCR and western blot. The level changes of IL-1β, IL-6 and IL-8 in SPC-Al were also detected after the stimulation of TLRs agonists. Results： We found that the phenotype markers of TAMs were highly expressed after stimulating human monocyte cell line THP-1 by phorbol-12-myristate-β-acetate （PMA）. Higher mRNA and supernate secretion levels of IL-1β, IL-6 and IL-8 were detected in SPC-A1 after being eocultured with TAMs. We also found that TLR1, TLR6 and TLR7 were up-regulated in SPC-A1 in the coculture system with TAMs. Meanwhile, TLRs signaling pathway proteins were also significantly activated. Moreover, pre-treatment with agonist ligands for TLR1, TLR6 and TLR7 could dramatically promote inductions of IL-1β, IL-6 and IL-8. Conclusions： These findings demonstrated that TAMs may enhance IL-1β, IL-6 and IL-8 expressions via TLRs signaling pathway. We conclude that TAMs contribute to maintain the inflammation microenvironment and ultimately promote the development and progression of lung cancer.
基金This study is in part funded by grants P01HD054713,R56AI124356,and 3N01 HD23342 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development,National Institutes of Health,Department of Health and Human Services.
文摘Pregnancy is a unique immunologic and microbial condition that requires an adequate level of awareness to provide a fast and protective response against pathogens as well as to maintain a state of tolerance to paternal antigens.Dysregulation of inflammatory pathways in the placenta triggered by pathogens is one of the main factors responsible for pregnancy complications.Type I IFNs are key molecules modulating immune responses at the level of the placenta and are crucial for protection of the pregnancy via their antiviral and immune modulatory properties.In this study,we elucidate the mechanisms controlling the basal expression of IFNβand its negative feedback.Using in vitro and in vivo animal models,we found that TLR signaling maintains basal IFNβlevels through the TLR4-MyD88-independent TBK/IRF3 signaling pathway.We describe the role of the TAM receptor Axl in the regulation of IFNβfunction in human and mouse trophoblast cells.The absence of TAM receptors in vivo is associated with fetal demise due to dysregulation of IFNβexpression and its pro-apoptotic downstream effectors.Collectively,our data describe a feedback signaling pathway controlling the expression and function of IFNβin the trophoblast that is essential for an effective response during viral and microbial infections.
文摘目的:观察柴胡疏肝散联合他莫昔芬对大鼠乳腺增生的干预作用。方法:50只随机大鼠分为对照组,模型组,柴胡疏肝散(6.3 g·kg^(-1))组,他莫昔芬(1.67 mg·kg^(-1))组,柴胡疏肝散+他莫昔芬组。采用夹尾激怒法制备大鼠乳腺增生模型,灌胃给药30d。酶联免疫法测定血清雌二醇,孕酮和催乳素,免疫组化法检测乳腺组织中雌激素受体及孕激素受体的表达。结果:与模型组比较,柴胡疏肝散联合他莫昔芬组大鼠血清中催乳素[(837.223±34.163)μg·L-1vs(346.215±43.114)μg·L-1,P<0.05]、雌二醇[(15.713±1.231)ng·L-1vs(4.973±0.278)ng·L-1,P<0.05)]的含量有效降低,孕酮[(0.423±0.031)μg·L-1vs(1.235±0.096)μg·L-1,P<0.05)]的含量提高;乳腺组织中雌激素受体表达显著被抑制(7.462±0.534 vs 4.889±0.343,P<0.05),孕激素受体的表达显著增强(1.212±0.53 vs 2.232±0.415,P<0.05)。结论:柴胡疏肝散联合他莫昔芬对大鼠乳腺增生有明显干预作用。
