Fructose and glucose are often widely used in food processing and may contribute to many metabolic diseases.To observe the effects of different doses of glucose and fructose on human metabolism and cellular communicat...Fructose and glucose are often widely used in food processing and may contribute to many metabolic diseases.To observe the effects of different doses of glucose and fructose on human metabolism and cellular communication,volunteers were given low,medium,and high doses of glucose and fructose.Serum cytokines,glucose,lactate,nicotinamide adenine dinucleotide(NADH)and metabolic enzymes were assayed,and central carbon metabolic pathway networks and cytokine communication networks were constructed.The results showed that the glucose and fructose groups basically maintained the trend of decreasing catabolism and increasing anabolism with increasing dose.Compared with glucose,low-dose fructose decreased catabolism and increased anabolism,significantly enhanced the expression of the inflammatory cytokine interferon-γ(IFN-γ),macrophage-derived chemokine(MDC),induced protein-10(IP-10),and eotaxin,and significantly reduced the activity of isocitrate dehydrogenase(ICDH)and pyruvate dehydrogenase complexes(PDHC).Both medium and high doses of fructose increase catabolism and anabolism,and there are more cytokines and enzymes with significant changes.Furthermore,multiple cytokines and enzymes show strong relevance to metabolic regulation by altering the transcription and expression of enzymes in central carbon metabolic pathways.Therefore,excessive intake of fructose should be reduced to avoid excessive inflammatory responses,allergic reactions and autoimmune diseases.展开更多
Background Changes in macrophage function are crucial contributors to hepatic inflammation and fibrosis.However,the role of macrophages in the development of liver fibrosis in dairy cows with ketosis remains unclear.T...Background Changes in macrophage function are crucial contributors to hepatic inflammation and fibrosis.However,the role of macrophages in the development of liver fibrosis in dairy cows with ketosis remains unclear.This study integrated proteomics and cytokine array approach to identify the multifactorial and multicellular interaction effects driving liver fibrosis in dairy cows with ketosis and analyze the mechanism by which the proinflammatory shift in macrophages contributes to liver fibrosis.Results Histopathological analysis revealed liver injury,including severe steatosis,infiltration of inflammatory cells,an increase in lipid deposition,and a decrease in glycogen expression in ketotic cows.Moreover,the number of mitochondria considerably increased in hepatocytes.The activation of the dynamin-related protein 1/mitochondrial fission factor(DRP1/MFF)pathway induced excessive mitochondrial fission,and the inhibition of the nuclear factor erythroid 2-related factor 2/heme oxygenase 1(Nrf2/HO-1)pathway led to the accumulation of intracellular reactive oxygen species(ROS).Proteomic analysis revealed the activation of extracellular matrix(ECM)-related functions and the NF-κB pathway in the liver,whereas cytokine array analysis revealed that the cytokine network was dysregulated.The accumulation of ROS triggered NF-κB nuclear translocation,inducing a proinflammatory shift in macrophages and liver inflammation.M1 polarization of macrophages promotes the release of proinflammatory mediators,which stimulated hepatic stellate cells(HSCs)activation,leading to ECM deposition,ultimately contributing to liver fibrosis.Conclusions To summarize,our study revealed the multifactorial and multicellular interaction effects driving liver fibrosis.Our results preliminarily showed that increased mitochondrial fission and inhibition of the Nrf2/HO-1 pathway are key factors in activating macrophages,which can lead to liver fibrosis in dairy cows with ketosis.展开更多
Immunobiological study is a key to revealing the important basis of facial nerve repair and regeneration for both research and development of clinic treatments. The microenvironmental changes around an injuried facial...Immunobiological study is a key to revealing the important basis of facial nerve repair and regeneration for both research and development of clinic treatments. The microenvironmental changes around an injuried facial motoneuron, i.e., the aggregation and expression of various types of immune cells and molecules in a dynamic equilibrium, impenetrate from the start to the end of the repair of an injured facial nerve. The concept of 'immune microenvironment for facial nerve repair and regeneration', mainly concerns with the dynamic exchange between expression and regulation networks and a variaty of immune cells and immune molecules in the process of facial nerve repair and regeneration for the maintenance of a immune microenvironment favorable for nerve repair. Investigation on microglial activation and recruitment, T cell behavior, cytokine networks, and immunological cellular and molecular signaling pathways in facial nerve repair and regeneration are the current hot spots in the research on immunobiology of facial nerve injury. The current paper provides a comprehensive review of the above mentioned issues. Research of these issues will eventually make immunological interventions practicable treatments for facial nerve injury in the clinic.展开更多
Objective To study the molecular biology mechanism of Danggui-buxue-tang on tonifying Qi and controlling blood circulation through modulation the immune functional genes.Methods Rats were randomly divided into control...Objective To study the molecular biology mechanism of Danggui-buxue-tang on tonifying Qi and controlling blood circulation through modulation the immune functional genes.Methods Rats were randomly divided into control group,model group,and Danggui-buxue-tang group.Effect of Dang-guibuxue-tang on mRNA expressions of IL-1β,TNF-α,HSP-70,NF-κB,p38MAPK and JNK in blood cells of rats with Qi deficiency and blood stasis were measured with real-time fluorescent quantitative-PCR at 5th,14th and 28th day.And that in artery wall were determined at the 28th day.NF-κB/p65 and p-c-jun protein expressions in rat artery wall were detected by western blotting as well.Results In model group,TNF-α,IL-1β,NF-κB,HSP-70,p38MAPK and JNK mRNA expression in blood cell increased significantly compared with control group.Compared with model group,mRNA expression of IL-1βand JNK decreased significantly;TNF-αdecreased at 5th,14th day;HSP-70,p38MAPK decreased at 14th,28th day;NF-κB decreased at 28th day.In model group,TNF-α,IL-1β,NF-κB,p38MAPK and JNK mRNA expression in artery increased compared with control group,excluded HSP-70,and that in Danggui-buxue-tang group decreased significantly.In model group,NF-κB/p65 and p-c-jun protein expression in artery increased compared with control group,and that in Danggui-buxue-tang group decreased significantly.Conclusions The effects of Dang-guibuxue-tang on Qi deficiency and blood stasis syndrome was brought from the regulating of cytokine network at multi-link and multi-target,NF-κB,p38MAPK and JNK signal transduction pathways included.Through which the immune system and whole body reached to a functional balance status.展开更多
Obesity-related asthma is a distinct clinical phenotype,characterized by severe respiratory symptoms,reduced responsiveness to conventional glucocorticoid therapy,and a significantly increase in disease burden.With th...Obesity-related asthma is a distinct clinical phenotype,characterized by severe respiratory symptoms,reduced responsiveness to conventional glucocorticoid therapy,and a significantly increase in disease burden.With the rising global prevalence of obesity,the number of individuals affected by obesity-related asthma is steadily growing,presenting a pressing public health issue.The pathogenesis of obesity-related asthma is multifactorial,involving a complex interplay of metabolic and immune pathways.Key mechanisms include dysregulated T-cell differentiation,pro-inflammatory macrophage polarization,oxidative stress,and altered cytokines and adipokines secretion,all contributing to airway inflammation and remodeling.Additionally,metabolic factors,such as adiposity and adipokine imbalance,further complicated disease progression.A major clinical challenge is developing targeted therapies to address the substantial heterogeneity in this patient population.Current treatment approaches,largely focused on corticosteroids,often fail to achieve satisfactory outcomes,emphasizing the need for novel,tailored therapies that target the specific pathophysiological features of obesity-related asthma.This review systematically explores the cellular and molecular mechanisms driving obesity-related asthma,focusing on how obesity-associated factors such as adipokines and airway remodeling influence disease progression.The review also evaluates emerging therapeutic interventions and highlights the ongoing challenges in clinical diagnosis and management.By synthesizing recent research,this study aims to provide insights into potential strategies for improving treatment and clinical outcomes for patients with obesity-related asthma.展开更多
Tuberculosis(TB),caused by Mycobacterium tuberculosis(Mtb),remains a global health challenge.Arginine metabolism is central to immune responses,regulating nitric oxide(NO)production via inducible NO synthase(Nos2)and ...Tuberculosis(TB),caused by Mycobacterium tuberculosis(Mtb),remains a global health challenge.Arginine metabolism is central to immune responses,regulating nitric oxide(NO)production via inducible NO synthase(Nos2)and competing pathways mediated by arginases(Arg1 and Arg2).This study examines the impact of arginine supplementation and arginase inhibition during the acute phase of Mtb infection in mouse lungs,focusing on immune function,lung pathology,and mitochondrial function.Arginine supplementation enhanced Nos2 expression,promoted mitophagy,and supported angiogenesis and/or tissue repair by upregulating Vegfa.These mechanisms synergized to balance pro-inflammatory responses with tissue repair,improving immune defense while mitigating lung damage.In contrast,arginase inhibition disrupted Vegfa-mediated immune homeostasis,and impaired mitophagy,leading to exacerbated lung pathology.These findings underscore the complementary roles of Nos2 and arginase-mediated pathways in maintaining immune equilibrium during Mtb infection.Our results highlight arginine supplementation as a promising host-directed therapy for TB,capable of enhancing protective immunity and facilitating tissue repair.Conversely,caution is warranted for strategies targeting arginase due to potential adverse effects on inflammation resolution and mitochondrial quality control.Future studies should explore the long-term efficacy of arginine-based therapies and their integration with existing antibiotic regimens for optimal TB management.展开更多
Objective：To explore the pharmacological anti-inflammatory mechanism of Chinese formula Qingwen Baidu Decoction（清瘟败毒饮,QBD） from the view of holistic biology.Methods：The rats were randomly divided into a norma...Objective：To explore the pharmacological anti-inflammatory mechanism of Chinese formula Qingwen Baidu Decoction（清瘟败毒饮,QBD） from the view of holistic biology.Methods：The rats were randomly divided into a normal conrol group,a lipopolysaccharide（LPS） group,the low- and high-dose QBD groups,and a dexamethasone（DXM） group.NR8383 cells were treated with culture fluid containing 6%serum from rats of each group respectively.Inflammatory mediators were detected by reverse transcription polymerase chain reaction（RT-PCR）,Western blotting hybridization,enzyme linked immunosorbent assay（ELISA）,polymerase chain reaction（PCR） gene array and antibody array.Results：It is showed that the levels of interleukin（IL）-1 α,IL-4 and IL-12 were enhanced in the low-dose QBD group;levels of IL-1 α,IL-12 and IL-18 were augmented in the high-dose QBD group,compared with the LPS group after ELISA detection.Western blot showed that IL-1β and tumor necrosis factor（TNF）-α expression of the control group were lower than other groups.IL-1 βlevel of the low-dose and high-dose QBD groups detected by RT-PCR was higher in early stage but lower after24 h than that of the control group（P〈0.01）.Expression of 84 main inflammatory cytokines and receptors was detected by rat inflammatory cytokines and receptors PCR array.Up-regulation genes were 22 in both the LPS group and the low-dose QBD group,among which 16 up-regulating genes were the same.In these 16 genes,the up-regulating amplitude of 9 genes in the low-dose QBD group was less than that in the LPS group,4 were similar to and 3 were more.Twenty-nine main cytokines were inspected by rat cytokine antibody array.Intergroup gray value differences were found in 7 expressed cytokines.The levels of these 7 cytokines in the lowdose QBD group were all lower than those in the the LPS group.Conclusions：QBD has anti-inflammatory effect on sepsis by changing the level of inflammatory mediators.展开更多
In 2005,a new lineage of helper T cells was discovered-Th17 cells-as reported in Nature Immunology,a breakthrough that fundamentally transformed our understanding of immune regulation.This discovery challenged the the...In 2005,a new lineage of helper T cells was discovered-Th17 cells-as reported in Nature Immunology,a breakthrough that fundamentally transformed our understanding of immune regulation.This discovery challenged the then-dominant Th1/Th2 paradigm and unveiled an entirely new scenario of immune complexity,particularly in inflammation,host defense,and autoimmunity.Few findings in the past two decades have had such a broad and lasting impact on basic and translational immunology.Th17 has shaped how we understand cytokine networks,immune regulation,and autoimmunity.In October 2025,a dialogue titled“Twenty years of Th17:A dialogue on immunological innovation and translation”was held during the 2025 CSBMB Annual Symposium to commemorate this milestone.Professor Dong reflected on the origins and impact of Th17 research,its integration into the broader immune regulatory network,and his vision for the next two decades.展开更多
基金financially supported by National Natural Science Foundation of China(31901782)。
文摘Fructose and glucose are often widely used in food processing and may contribute to many metabolic diseases.To observe the effects of different doses of glucose and fructose on human metabolism and cellular communication,volunteers were given low,medium,and high doses of glucose and fructose.Serum cytokines,glucose,lactate,nicotinamide adenine dinucleotide(NADH)and metabolic enzymes were assayed,and central carbon metabolic pathway networks and cytokine communication networks were constructed.The results showed that the glucose and fructose groups basically maintained the trend of decreasing catabolism and increasing anabolism with increasing dose.Compared with glucose,low-dose fructose decreased catabolism and increased anabolism,significantly enhanced the expression of the inflammatory cytokine interferon-γ(IFN-γ),macrophage-derived chemokine(MDC),induced protein-10(IP-10),and eotaxin,and significantly reduced the activity of isocitrate dehydrogenase(ICDH)and pyruvate dehydrogenase complexes(PDHC).Both medium and high doses of fructose increase catabolism and anabolism,and there are more cytokines and enzymes with significant changes.Furthermore,multiple cytokines and enzymes show strong relevance to metabolic regulation by altering the transcription and expression of enzymes in central carbon metabolic pathways.Therefore,excessive intake of fructose should be reduced to avoid excessive inflammatory responses,allergic reactions and autoimmune diseases.
基金supported by the National Natural Science Foundation of China(32125038 and 32402957)China National Postdoctoral Program for Innovative Talents(BX20240417)+1 种基金China Postdoctoral Science Foundation funded project(2024M753563)National Key Research and Development Program of China(2023YFD1801100).
文摘Background Changes in macrophage function are crucial contributors to hepatic inflammation and fibrosis.However,the role of macrophages in the development of liver fibrosis in dairy cows with ketosis remains unclear.This study integrated proteomics and cytokine array approach to identify the multifactorial and multicellular interaction effects driving liver fibrosis in dairy cows with ketosis and analyze the mechanism by which the proinflammatory shift in macrophages contributes to liver fibrosis.Results Histopathological analysis revealed liver injury,including severe steatosis,infiltration of inflammatory cells,an increase in lipid deposition,and a decrease in glycogen expression in ketotic cows.Moreover,the number of mitochondria considerably increased in hepatocytes.The activation of the dynamin-related protein 1/mitochondrial fission factor(DRP1/MFF)pathway induced excessive mitochondrial fission,and the inhibition of the nuclear factor erythroid 2-related factor 2/heme oxygenase 1(Nrf2/HO-1)pathway led to the accumulation of intracellular reactive oxygen species(ROS).Proteomic analysis revealed the activation of extracellular matrix(ECM)-related functions and the NF-κB pathway in the liver,whereas cytokine array analysis revealed that the cytokine network was dysregulated.The accumulation of ROS triggered NF-κB nuclear translocation,inducing a proinflammatory shift in macrophages and liver inflammation.M1 polarization of macrophages promotes the release of proinflammatory mediators,which stimulated hepatic stellate cells(HSCs)activation,leading to ECM deposition,ultimately contributing to liver fibrosis.Conclusions To summarize,our study revealed the multifactorial and multicellular interaction effects driving liver fibrosis.Our results preliminarily showed that increased mitochondrial fission and inhibition of the Nrf2/HO-1 pathway are key factors in activating macrophages,which can lead to liver fibrosis in dairy cows with ketosis.
文摘Immunobiological study is a key to revealing the important basis of facial nerve repair and regeneration for both research and development of clinic treatments. The microenvironmental changes around an injuried facial motoneuron, i.e., the aggregation and expression of various types of immune cells and molecules in a dynamic equilibrium, impenetrate from the start to the end of the repair of an injured facial nerve. The concept of 'immune microenvironment for facial nerve repair and regeneration', mainly concerns with the dynamic exchange between expression and regulation networks and a variaty of immune cells and immune molecules in the process of facial nerve repair and regeneration for the maintenance of a immune microenvironment favorable for nerve repair. Investigation on microglial activation and recruitment, T cell behavior, cytokine networks, and immunological cellular and molecular signaling pathways in facial nerve repair and regeneration are the current hot spots in the research on immunobiology of facial nerve injury. The current paper provides a comprehensive review of the above mentioned issues. Research of these issues will eventually make immunological interventions practicable treatments for facial nerve injury in the clinic.
文摘Objective To study the molecular biology mechanism of Danggui-buxue-tang on tonifying Qi and controlling blood circulation through modulation the immune functional genes.Methods Rats were randomly divided into control group,model group,and Danggui-buxue-tang group.Effect of Dang-guibuxue-tang on mRNA expressions of IL-1β,TNF-α,HSP-70,NF-κB,p38MAPK and JNK in blood cells of rats with Qi deficiency and blood stasis were measured with real-time fluorescent quantitative-PCR at 5th,14th and 28th day.And that in artery wall were determined at the 28th day.NF-κB/p65 and p-c-jun protein expressions in rat artery wall were detected by western blotting as well.Results In model group,TNF-α,IL-1β,NF-κB,HSP-70,p38MAPK and JNK mRNA expression in blood cell increased significantly compared with control group.Compared with model group,mRNA expression of IL-1βand JNK decreased significantly;TNF-αdecreased at 5th,14th day;HSP-70,p38MAPK decreased at 14th,28th day;NF-κB decreased at 28th day.In model group,TNF-α,IL-1β,NF-κB,p38MAPK and JNK mRNA expression in artery increased compared with control group,excluded HSP-70,and that in Danggui-buxue-tang group decreased significantly.In model group,NF-κB/p65 and p-c-jun protein expression in artery increased compared with control group,and that in Danggui-buxue-tang group decreased significantly.Conclusions The effects of Dang-guibuxue-tang on Qi deficiency and blood stasis syndrome was brought from the regulating of cytokine network at multi-link and multi-target,NF-κB,p38MAPK and JNK signal transduction pathways included.Through which the immune system and whole body reached to a functional balance status.
基金supported by the Pediatric Medicine Phase Ⅱ Scientific Research Special Fund of the Jiangsu Medical Association(Grant No.SYH-32034-0106[2024010])the Wuxi Science and Technology Development Fund(Grant No.K20241001).
文摘Obesity-related asthma is a distinct clinical phenotype,characterized by severe respiratory symptoms,reduced responsiveness to conventional glucocorticoid therapy,and a significantly increase in disease burden.With the rising global prevalence of obesity,the number of individuals affected by obesity-related asthma is steadily growing,presenting a pressing public health issue.The pathogenesis of obesity-related asthma is multifactorial,involving a complex interplay of metabolic and immune pathways.Key mechanisms include dysregulated T-cell differentiation,pro-inflammatory macrophage polarization,oxidative stress,and altered cytokines and adipokines secretion,all contributing to airway inflammation and remodeling.Additionally,metabolic factors,such as adiposity and adipokine imbalance,further complicated disease progression.A major clinical challenge is developing targeted therapies to address the substantial heterogeneity in this patient population.Current treatment approaches,largely focused on corticosteroids,often fail to achieve satisfactory outcomes,emphasizing the need for novel,tailored therapies that target the specific pathophysiological features of obesity-related asthma.This review systematically explores the cellular and molecular mechanisms driving obesity-related asthma,focusing on how obesity-associated factors such as adipokines and airway remodeling influence disease progression.The review also evaluates emerging therapeutic interventions and highlights the ongoing challenges in clinical diagnosis and management.By synthesizing recent research,this study aims to provide insights into potential strategies for improving treatment and clinical outcomes for patients with obesity-related asthma.
基金supported in part by the National Institutes of Health(NIH)grants R21AI163824 and R21AI180662(L.S.)R01AI127844(L.S.and S.S.).
文摘Tuberculosis(TB),caused by Mycobacterium tuberculosis(Mtb),remains a global health challenge.Arginine metabolism is central to immune responses,regulating nitric oxide(NO)production via inducible NO synthase(Nos2)and competing pathways mediated by arginases(Arg1 and Arg2).This study examines the impact of arginine supplementation and arginase inhibition during the acute phase of Mtb infection in mouse lungs,focusing on immune function,lung pathology,and mitochondrial function.Arginine supplementation enhanced Nos2 expression,promoted mitophagy,and supported angiogenesis and/or tissue repair by upregulating Vegfa.These mechanisms synergized to balance pro-inflammatory responses with tissue repair,improving immune defense while mitigating lung damage.In contrast,arginase inhibition disrupted Vegfa-mediated immune homeostasis,and impaired mitophagy,leading to exacerbated lung pathology.These findings underscore the complementary roles of Nos2 and arginase-mediated pathways in maintaining immune equilibrium during Mtb infection.Our results highlight arginine supplementation as a promising host-directed therapy for TB,capable of enhancing protective immunity and facilitating tissue repair.Conversely,caution is warranted for strategies targeting arginase due to potential adverse effects on inflammation resolution and mitochondrial quality control.Future studies should explore the long-term efficacy of arginine-based therapies and their integration with existing antibiotic regimens for optimal TB management.
基金Supported by National Natural Science Foundation of China(No.30801468)
文摘Objective：To explore the pharmacological anti-inflammatory mechanism of Chinese formula Qingwen Baidu Decoction（清瘟败毒饮,QBD） from the view of holistic biology.Methods：The rats were randomly divided into a normal conrol group,a lipopolysaccharide（LPS） group,the low- and high-dose QBD groups,and a dexamethasone（DXM） group.NR8383 cells were treated with culture fluid containing 6%serum from rats of each group respectively.Inflammatory mediators were detected by reverse transcription polymerase chain reaction（RT-PCR）,Western blotting hybridization,enzyme linked immunosorbent assay（ELISA）,polymerase chain reaction（PCR） gene array and antibody array.Results：It is showed that the levels of interleukin（IL）-1 α,IL-4 and IL-12 were enhanced in the low-dose QBD group;levels of IL-1 α,IL-12 and IL-18 were augmented in the high-dose QBD group,compared with the LPS group after ELISA detection.Western blot showed that IL-1β and tumor necrosis factor（TNF）-α expression of the control group were lower than other groups.IL-1 βlevel of the low-dose and high-dose QBD groups detected by RT-PCR was higher in early stage but lower after24 h than that of the control group（P〈0.01）.Expression of 84 main inflammatory cytokines and receptors was detected by rat inflammatory cytokines and receptors PCR array.Up-regulation genes were 22 in both the LPS group and the low-dose QBD group,among which 16 up-regulating genes were the same.In these 16 genes,the up-regulating amplitude of 9 genes in the low-dose QBD group was less than that in the LPS group,4 were similar to and 3 were more.Twenty-nine main cytokines were inspected by rat cytokine antibody array.Intergroup gray value differences were found in 7 expressed cytokines.The levels of these 7 cytokines in the lowdose QBD group were all lower than those in the the LPS group.Conclusions：QBD has anti-inflammatory effect on sepsis by changing the level of inflammatory mediators.
文摘In 2005,a new lineage of helper T cells was discovered-Th17 cells-as reported in Nature Immunology,a breakthrough that fundamentally transformed our understanding of immune regulation.This discovery challenged the then-dominant Th1/Th2 paradigm and unveiled an entirely new scenario of immune complexity,particularly in inflammation,host defense,and autoimmunity.Few findings in the past two decades have had such a broad and lasting impact on basic and translational immunology.Th17 has shaped how we understand cytokine networks,immune regulation,and autoimmunity.In October 2025,a dialogue titled“Twenty years of Th17:A dialogue on immunological innovation and translation”was held during the 2025 CSBMB Annual Symposium to commemorate this milestone.Professor Dong reflected on the origins and impact of Th17 research,its integration into the broader immune regulatory network,and his vision for the next two decades.
