Proton-activated G protein-coupled receptors(GPCRs),initially discovered by Ludwig in 2003,are widely distributed in various tissues.These receptors have been found to modulate the immune system in several inflammator...Proton-activated G protein-coupled receptors(GPCRs),initially discovered by Ludwig in 2003,are widely distributed in various tissues.These receptors have been found to modulate the immune system in several inflammatory diseases,including inflammatory bowel disease,atopic dermatitis,and asthma.Proton-activated GPCRs belong to the G protein-coupled receptor family and can detect alternations in extracellular pH.This detection triggers downstream signaling pathways within the cells,ultimately influencing the function of immune cells.In this review,we specifically focused on investigating the immune response of proton-activated GPCRs under inflammatory conditions.展开更多
Introduction: Autoimmune blistering skin disorders such as Bullous Pemphigoid and Pemphigus Vulgaris present diagnostic challenges. The Systemic Immune-Inflammation Index (SII) and Neutrophil-Lymphocyte Ratio (NLR), a...Introduction: Autoimmune blistering skin disorders such as Bullous Pemphigoid and Pemphigus Vulgaris present diagnostic challenges. The Systemic Immune-Inflammation Index (SII) and Neutrophil-Lymphocyte Ratio (NLR), are inflammatory markers used to assess the body’s immune-inflammatory response. Objectives: The study aims to evaluate the significance of hematologic markers, specifically the Systemic Immune-Inflammation Index (SII) and Neutrophil-Lymphocyte Ratio (NLR), as diagnostic predictors of bullous pemphigoid (BP) and pemphigus vulgaris (PV). Methods: A retrospective study of 64 patients (36 with BP and 28 with PV). Patient clinical data: age, gender, complete blood count, autoimmune antibody levels (Dsg1, 3 and BP180, 230), IgE and C-reactive protein, and history of hypertension, diabetes, brain infarction, and coronary heart disease. The data was analyzed using SPSS. Results: The study involved 36 (56.3%) diagnosed with bullous pemphigoid (BP) and 28 (43.75%) with pemphigus vulgaris (PV). The average age in BP was 71 ± 8 and 52 ± 13 in PV. Laboratory findings showed high levels of Dsg1, Dsg3, neutrophil count, and lymphocyte count in PV, while high levels of eosinophils with a significant increase in C-reactive protein (CRP) in BP. Blood biomarkers, including NLR, PLR, SII, MPV, CRP, and IgE, proved an overall of 84.4% in disease prediction. Dsg1, Dsg3, BP180, and BP230 showed an overall of 88.1%. No significant relationship was noted between NLR, SII, and patients with comorbidities. Conclusion: The study highlights the diagnostic potential of SII and NLR in addition to hematologic markers in BP and PV, emphasizing their role in early diagnosis and therapeutic interventions, requiring further validation in larger patient cohorts.展开更多
Pre-diabetic insulin resistance is associated with sub-clinical inflammation and concomitant increase in systemic C-reactive protein(CRP)levels.Type 2 diabetes mellitus(T2DM)patients register even higher chronic level...Pre-diabetic insulin resistance is associated with sub-clinical inflammation and concomitant increase in systemic C-reactive protein(CRP)levels.Type 2 diabetes mellitus(T2DM)patients register even higher chronic levels of inflammation,with excess circulating CRP originating from both typical hepatic synthesis,and also visceral white adipose tissue.展开更多
Cellular senescence assumes pivotal roles in various diseases through the secretion of proinflammatory factors.Despite extensive investigations into vascular senescence associated with aging and degenerative diseases,...Cellular senescence assumes pivotal roles in various diseases through the secretion of proinflammatory factors.Despite extensive investigations into vascular senescence associated with aging and degenerative diseases,the molecular mechanisms governing microvascular endothelial cell senescence induced by traumatic stress,particularly its involvement in senescence-induced inflammation,remain insufficiently elucidated.In this study,we present a comprehensive demonstration and characterization of microvascular endothelial cell senescence induced by spinal cord injury(SCI).Lysine demethylase 6A(Kdm6a),commonly known as UTX,emerges as a crucial regulator of cell senescence in injured spinal cord microvascular endothelial cells(SCMECs).Upregulation of UTX induces senescence in SCMECs,leading to an amplified release of proinflammatory factors,specifically the senescenceassociated secretory phenotype(SASP)components,thereby modulating the inflammatory microenvironment.Conversely,the deletion of UTX in endothelial cells shields SCMECs against senescence,mitigates the release of proinflammatory SASP factors,and promotes neurological functional recovery after SCI.UTX forms an epigenetic regulatory axis by binding to calponin 1(CNN1),orchestrating trauma-induced SCMECs senescence and SASP secretion,thereby influencing neuroinflammation and neurological functional repair.Furthermore,local delivery of a senolytic drug reduces senescent SCMECs and suppresses proinflammatory SASP secretion,reinstating a local regenerative microenvironment and enhancing functional repair after SCI.In conclusion,targeting the UTX-CNN1 epigenetic axis to prevent trauma-induced SCMECs senescence holds the potential to inhibit SASP secretion,alleviate neuroinflammation,and provide a novel treatment strategy for SCI repair.展开更多
BACKGROUND Studies have demonstrated the influence of immunity and inflammation on the development of tumors.Although single biomarkers of immunity and inflam-mation have been shown to be clinically predictive,the use...BACKGROUND Studies have demonstrated the influence of immunity and inflammation on the development of tumors.Although single biomarkers of immunity and inflam-mation have been shown to be clinically predictive,the use of biomarkers integrating both to predict prognosis in patients with gastric cancer remains to be investigated.AIM To investigate the prognostic and clinical significance of inflammatory biomarkers and lymphocytes in patients undergoing surgical treatment for gastric cancer.METHODS Univariate COX regression analysis was performed to identify potential prognostic factors for patients with gastric cancer undergoing surgical treatment.Least absolute shrinkage and selection operator-COX(LASSO-COX)regression analysis was performed to integrate these factors and formulate a new prognostic immunoinflammatory index(PII).The correlation between PII and clinical charac-teristics was statistically analyzed.Nomograms incorporating the PII score were devised and validated based on the time-dependent area under the curve and decision curve analysis.RESULTS Patients exhibiting elevated neutrophil-to-lymphocyte ratio,platelet-to-lymphocyte ratio,and systemic immune inflammatory index displayed inferior progression-free survival(PFS)and overall survival(OS).Conversely,low levels of CD3(+),CD3(+)CD8(+),CD4(+)CD8(+),and CD3(+)CD16(+)CD56(+)T lymphocytes were associated with improved PFS and OS,while high CD19(+)T lymphocyte levels were linked to worse PFS and OS.The PII score demonstrated associations with tumor characteristics(primary tumor site and tumor size),establishing itself as an independent prognostic factor for both PFS and OS.Time-dependent area under the curve and decision curve analysis affirmed the effectiveness of the PII-based nomogram as a robust prognostic predictive model.CONCLUSION PII may be a reliable predictor of prognosis in patients with gastric cancer undergoing surgical treatment,and it offers insights into cancer-related immune-inflammatory responses,with potential significance in clinical practice.展开更多
Objective:To evaluate the effect of the ethyl acetate fraction derived from Sargassum pallidum extract against particulate matter(PM)-induced oxidative stress and inflammation in HaCaT cells and zebrafish.Methods:HaCa...Objective:To evaluate the effect of the ethyl acetate fraction derived from Sargassum pallidum extract against particulate matter(PM)-induced oxidative stress and inflammation in HaCaT cells and zebrafish.Methods:HaCaT cells and zebrafish were used to evaluate the protective effects of the ethyl acetate fraction of Sargassum pallidum extract against PM-induced oxidative stress and inflammation.The production of nitric oxide(NO),intracellular ROS,prostaglandin E_(2)(PGE_(2)),and pro-inflammatory cytokines,and the expression levels of COX-2,iNOS,and NF-κB were evaluated in PM-induced HaCaT cells.Furthermore,the levels of ROS,NO,and lipid peroxidation were assessed in the PM-exposed zebrafish model.Results:The ethyl acetate fraction of Sargassum pallidum extract significantly decreased the production of NO,intracellular ROS,and PGE_(2) in PM-induced HaCaT cells.In addition,the fraction markedly suppressed the levels of pro-inflammatory cytokines and inhibited the expression levels of COX-2,iNOS,and NF-κB.Furthermore,it displayed remarkable protective effects against PM-induced inflammatory response and oxidative stress,represented by the reduction of NO,ROS,and lipid peroxidation in zebrafish.Conclusions:The ethyl acetate fraction of Sargassum pallidum extract exhibits a protective effect against PM-induced oxidative stress and inflammation both in vitro and in vivo and has the potential as a candidate for the development of pharmaceutical and cosmeceutical products.展开更多
BACKGROUND The modified Xiaoyao San(MXS)formula is an adjuvant drug recommended by the National Health Commission of China for the treatment of liver cancer,which has the effect of preventing postoperative recurrence ...BACKGROUND The modified Xiaoyao San(MXS)formula is an adjuvant drug recommended by the National Health Commission of China for the treatment of liver cancer,which has the effect of preventing postoperative recurrence and metastasis of hepatocellular carcinoma and prolonging patient survival.However,the molecular mechanisms underlying that remain unclear.AIM To investigate the role and mechanisms of MXS in ameliorating hepatic injury,steatosis and inflammation.METHODS A choline-deficient/high-fat diet-induced rat nonalcoholic steatohepatitis(NASH)model was used to examine the effects of MXS on lipid accumulation in primary hepatocytes.Liver tissues were collected for western blotting and immunohisto chemistry(IHC)assays.Lipid accumulation and hepatic fibrosis were detected using oil red staining and Sirius red staining.The serum samples were collected for biochemical assays and NMR-based metabonomics analysis.The inflammation/lipid metabolism-related signaling and regulators in liver tissues were also detected to reveal the molecular mechanisms of MXS against NASH.RESULTS MXS showed a significant decrease in lipid accumulation and inflammatory response in hepatocytes under metabolic stress.The western blotting and IHC results indicated that MXS activated AMPK pathway but inhibited the expression of key regulators related to lipid accumulation,inflammation and hepatic fibrosis in the pathogenesis of NASH.The metabonomics analysis systemically indicated that the arachidonic acid metabolism and steroid hormone synthesis are the two main target metabolic pathways for MXS to ameliorate liver inflammation and hepatic steatosis.Mechanistically,we found that MXS protected against NASH by attenuating the sex hormone-related metabolism,especially the metabolism of male hormones.CONCLUSION MXS ameliorates inflammation and hepatic steatosis of NASH by inhibiting the metabolism of male hormones.Targeting male hormone related metabolic pathways may be the potential therapeutic approach for NASH.展开更多
Myeloproliferative neoplasms(MPN)are a group of diseases characterized by the clonal proliferation of hematopoietic progenitor or stem cells.They are clinically classifiable into four main diseases:chronic myeloid leu...Myeloproliferative neoplasms(MPN)are a group of diseases characterized by the clonal proliferation of hematopoietic progenitor or stem cells.They are clinically classifiable into four main diseases:chronic myeloid leukemia,essential thrombocythemia,polycythemia vera,and primary myelofibrosis.These pathologies are closely related to cardio-and cerebrovascular diseases due to the increased risk of arterial thrombosis,the most common underlying cause of acute myocardial infarction.Recent evidence shows that the classical Virchow triad(hypercoagulability,blood stasis,endothelial injury)might offer an explanation for such association.Indeed,patients with MPN might have a higher number and more reactive circulating platelets and leukocytes,a tendency toward blood stasis because of a high number of circulating red blood cells,endothelial injury or overactivation as a consequence of sustained inflammation caused by the neoplastic clonal cell.These abnormal cancer cells,especially when associated with the JAK2V617F mutation,tend to proliferate and secrete several inflammatory cytokines.This sustains a pro-inflammatory state throughout the body.The direct consequence is the induction of a pro-thrombotic state that acts as a determinant in favoring both venous and arterial thrombus formation.Clinically,MPN patients need to be carefully evaluated to be treated not only with cytoreductive treatments but also with cardiovascular protective strategies.展开更多
Inflammation is a multifaceted cellular and molecular response triggered by injury,infection,or various pathological conditions.Serving as a protective defense mechanism,the inflammatory response involves clinical sig...Inflammation is a multifaceted cellular and molecular response triggered by injury,infection,or various pathological conditions.Serving as a protective defense mechanism,the inflammatory response involves clinical signs like redness,swelling,pain,and increased body temperature.Immune cells,notably neutrophils and macrophages,play key roles in orchestrating this response.The delicate balance between proinflammatory and anti-inflammatory mediators,including cytokines and chemokines,regulates the inflammatory cascade.While acute inflammation is crucial for tissue repair,chronic inflammation may indicate an imbalance,contributing to conditions like autoimmune diseases.Understanding these mechanisms is vital for developing therapeutic strategies and managing chronic diseases.展开更多
We previously showed that hydrogen sulfide(H2S)has a neuroprotective effect in the context of hypoxic ischemic brain injury in neonatal mice.However,the precise mechanism underlying the role of H2S in this situation r...We previously showed that hydrogen sulfide(H2S)has a neuroprotective effect in the context of hypoxic ischemic brain injury in neonatal mice.However,the precise mechanism underlying the role of H2S in this situation remains unclear.In this study,we used a neonatal mouse model of hypoxic ischemic brain injury and a lipopolysaccharide-stimulated BV2 cell model and found that treatment with L-cysteine,a H2S precursor,attenuated the cerebral infarction and cerebral atrophy induced by hypoxia and ischemia and increased the expression of miR-9-5p and cystathionineβsynthase(a major H2S synthetase in the brain)in the prefrontal cortex.We also found that an miR-9-5p inhibitor blocked the expression of cystathionineβsynthase in the prefrontal cortex in mice with brain injury caused by hypoxia and ischemia.Furthermore,miR-9-5p overexpression increased cystathionine-β-synthase and H2S expression in the injured prefrontal cortex of mice with hypoxic ischemic brain injury.L-cysteine decreased the expression of CXCL11,an miR-9-5p target gene,in the prefrontal cortex of the mouse model and in lipopolysaccharide-stimulated BV-2 cells and increased the levels of proinflammatory cytokines BNIP3,FSTL1,SOCS2 and SOCS5,while treatment with an miR-9-5p inhibitor reversed these changes.These findings suggest that H2S can reduce neuroinflammation in a neonatal mouse model of hypoxic ischemic brain injury through regulating the miR-9-5p/CXCL11 axis and restoringβ-synthase expression,thereby playing a role in reducing neuroinflammation in hypoxic ischemic brain injury.展开更多
In neurodegenerative and classically demyelinating disorders such as multiple sclerosis(MS),spinal cord injury(SCI),stroke,and Charcot-Marie-Tooth disease,glial functioning is compromised and nervous tissue integrity ...In neurodegenerative and classically demyelinating disorders such as multiple sclerosis(MS),spinal cord injury(SCI),stroke,and Charcot-Marie-Tooth disease,glial functioning is compromised and nervous tissue integrity is lost.Recently,primary neurodegenerative disorders such as Alzheimer’s disease,amyotrophic lateral sclerosis(ALS),and Parkinson’s disease(PD)are increasingly linked to impaired oligodendroglia functioning upon neurodegeneration.Due to the destructive micro-environment created by nervous tissue damage,the progressive cellular loss in these disorders,and the amitotic nature of neurons,spontaneous endogenous repair process are limited in nature.Hence,there is a medical need for efficient therapeutic strategies capable of supporting neuro-reparative processes to occur,likely supported by improved oligodendroglia cell functioning.展开更多
Neuroimmunology is emerging as a pivotal field,shedding light on the intricate dialogues between the central nervous system(CNS)and the immune system.This exploration is particularly significant in understanding micro...Neuroimmunology is emerging as a pivotal field,shedding light on the intricate dialogues between the central nervous system(CNS)and the immune system.This exploration is particularly significant in understanding microglia,the CNS’s innate immune cells,beyond the conventional conflation of“neuroinflammation”and“microglial activation.”This conflation has clouded the true complexity of these processes,potentially stalling scientific progress and the development of new therapies.We challenge the long-standing perspectives that have oversimplified these interactions,advocating for a deeper exploration of the dynamic relationship between neuroinflammation and microglial activation.By dissecting specific molecular pathways,we aim to illuminate their elaborate roles in neuroinflammatory responses,especially in the context of Alzheimer’s disease(AD).Here,neuroinflammation is not merely a passive observer or a direct antagonist but a complex agent in the disease’s progression.This article calls for a significant paradigm shift towards an integrative,multi-omics approach to neuroimmunology.Adopting such a comprehensive framework is crucial for advancing our understanding of neuroinflammatory conditions and paving the way for targeted therapeutic strategies for brain diseases.展开更多
Brain organoids mimic closely the embryonic human brain:Over the last decade,the development of human organoid systems has evolved rapidly.Different tissues have been modeled with organoids,such as the gut,lung,liver,...Brain organoids mimic closely the embryonic human brain:Over the last decade,the development of human organoid systems has evolved rapidly.Different tissues have been modeled with organoids,such as the gut,lung,liver,kidney retina and brain.These systems have a high cellular heterogeneity,with many cell types integrated into the same system.Organoids'cellular populations interact between and amongst each other in a cellular and molecular level,which represents an advantage with respects to monolayer 2D cell culture systems.展开更多
Apical periodontitis(AP)is a dental-driven condition caused by pathogens and their toxins infecting the inner portion of the tooth(i.e.,dental pulp tissue),resulting in inflammation and apical bone resorption affectin...Apical periodontitis(AP)is a dental-driven condition caused by pathogens and their toxins infecting the inner portion of the tooth(i.e.,dental pulp tissue),resulting in inflammation and apical bone resorption affecting 50%of the worldwide population,with more than 15 million root canals performed annually in the United States.Current treatment involves cleaning and decontaminating the infected tissue with chemo-mechanical approaches and materials introduced years ago,such as calcium hydroxide,zinc oxide–eugenol,or even formalin products.Here,we present,for the first time,a nanotherapeutics based on using synthetic highdensity lipoprotein(sHDL)as an innovative and safe strategy to manage dental bone inflammation.sHDL application in concentrations ranging from 25μg to 100μg/mL decreases nuclear factor Kappa B(NF-κB)activation promoted by an inflammatory stimulus(lipopolysaccharide,LPS).Moreover,sHDL at 500μg/mL concentration markedly decreases in vitro osteoclastogenesis(P<0.001),and inhibits IL-1α(P=0.027),TNF-α(P=0.004),and IL-6(P<0.001)production in an inflammatory state.Notably,sHDL strongly dampens the Toll-Like Receptor signaling pathway facing LPS stimulation,mainly by downregulating at least 3-fold the pro-inflammatory genes,such as Il1b,Il1a,Il6,Ptgs2,and Tnf.In vivo,the lipoprotein nanoparticle applied after NaOCl reduced bone resorption volume to(1.3±0.05)mm^(3) and attenuated the inflammatory reaction after treatment to(1090±184)cells compared to non-treated animals that had(2.9±0.6)mm^(3)(P=0.0123)and(2443±931)cells(P=0.004),thus highlighting its promising clinical potential as an alternative therapeutic for managing dental bone inflammation.展开更多
Nowadays,roughly 603.7 million people are bothered by obesity[1].More seriously,obesity brings inflammation to the peripheral and central nervous system,which compromises the comorbidity of obesity,major depression[2]...Nowadays,roughly 603.7 million people are bothered by obesity[1].More seriously,obesity brings inflammation to the peripheral and central nervous system,which compromises the comorbidity of obesity,major depression[2],and cognitive deficits[3].Drug competent in the comorbidity is still lacking.In 2015,Liu et al.[4]reported celastrol(CEL)as a powerful anti-obesity agent.In our previous study.展开更多
In 1872, George Huntington presented his essay “On Chorea” to the Meigs and Mason Academy of Medicine and, in doing so, detailed a disease that would later bear his name. Huntington's disease(HD) is a genetic, n...In 1872, George Huntington presented his essay “On Chorea” to the Meigs and Mason Academy of Medicine and, in doing so, detailed a disease that would later bear his name. Huntington's disease(HD) is a genetic, neurodegenerative disease that manifests as the loss of motor control,cognitive impairment,and mood and psychiatric changes in paents.展开更多
Traumatic spinal cord injury(SCI)is a devastating exogenous injury with long-lasting consequences and a leading cause of death and disability worldwide.Advances in assistive technology,rehabilitative interventions,and...Traumatic spinal cord injury(SCI)is a devastating exogenous injury with long-lasting consequences and a leading cause of death and disability worldwide.Advances in assistive technology,rehabilitative interventions,and the ability to identify and intervene in secondary conditions have significantly increased the long-term survival rate of SCI patients,with some people even living well into their seventh or eighth decade.These survival changes have led neurotrauma researchers to examine how SCI interacts with brain aging.Public health and epidemiological data showed that patients with long-term SCI can have a lower life expectancy and quality of life,along with a higher risk of comorbidities and complications.展开更多
Introduction to human endogenous retrovirus type-W(HERV-W): Genomic inheritance from the past includes retroviral sequences that have been stably incorporated into our genomes and account for up to 8% of human DNA.
In the article entitled“Boeravinone B ameliorates allergic nasal inflammation by modulating the GATA-3/T-bet signaling pathway in a mouse model of allergic rhinitis”,published on pages 245-252,Issue 6,Volume 14 in A...In the article entitled“Boeravinone B ameliorates allergic nasal inflammation by modulating the GATA-3/T-bet signaling pathway in a mouse model of allergic rhinitis”,published on pages 245-252,Issue 6,Volume 14 in Asian Pacific Journal of Tropical Biomedicine,the weight number was misspelled as“18.5 g”on page 246,first line,under 2.2.Animals paragraph.The correct weight should be“(18.5±5)g”.展开更多
Aging is associated with chronic form of inflammation called inflammaging,which results from immune system changes.Inflammaging plays a crucial role in the pathogenesis of various neurodegenerative diseases(Dabravolsk...Aging is associated with chronic form of inflammation called inflammaging,which results from immune system changes.Inflammaging plays a crucial role in the pathogenesis of various neurodegenerative diseases(Dabravolski et al.,2022).Moreove r,aging-related inflammation can be triggered by disrupted mitophagy.展开更多
基金supported by the National Nature Science Foundation of China(No.81873694)the Key Research and Development Program of Hubei Province(No.2022BCA005)Knowledge Innovation Program of Wuhan Basic Research(No.2022020801010446).
文摘Proton-activated G protein-coupled receptors(GPCRs),initially discovered by Ludwig in 2003,are widely distributed in various tissues.These receptors have been found to modulate the immune system in several inflammatory diseases,including inflammatory bowel disease,atopic dermatitis,and asthma.Proton-activated GPCRs belong to the G protein-coupled receptor family and can detect alternations in extracellular pH.This detection triggers downstream signaling pathways within the cells,ultimately influencing the function of immune cells.In this review,we specifically focused on investigating the immune response of proton-activated GPCRs under inflammatory conditions.
文摘Introduction: Autoimmune blistering skin disorders such as Bullous Pemphigoid and Pemphigus Vulgaris present diagnostic challenges. The Systemic Immune-Inflammation Index (SII) and Neutrophil-Lymphocyte Ratio (NLR), are inflammatory markers used to assess the body’s immune-inflammatory response. Objectives: The study aims to evaluate the significance of hematologic markers, specifically the Systemic Immune-Inflammation Index (SII) and Neutrophil-Lymphocyte Ratio (NLR), as diagnostic predictors of bullous pemphigoid (BP) and pemphigus vulgaris (PV). Methods: A retrospective study of 64 patients (36 with BP and 28 with PV). Patient clinical data: age, gender, complete blood count, autoimmune antibody levels (Dsg1, 3 and BP180, 230), IgE and C-reactive protein, and history of hypertension, diabetes, brain infarction, and coronary heart disease. The data was analyzed using SPSS. Results: The study involved 36 (56.3%) diagnosed with bullous pemphigoid (BP) and 28 (43.75%) with pemphigus vulgaris (PV). The average age in BP was 71 ± 8 and 52 ± 13 in PV. Laboratory findings showed high levels of Dsg1, Dsg3, neutrophil count, and lymphocyte count in PV, while high levels of eosinophils with a significant increase in C-reactive protein (CRP) in BP. Blood biomarkers, including NLR, PLR, SII, MPV, CRP, and IgE, proved an overall of 84.4% in disease prediction. Dsg1, Dsg3, BP180, and BP230 showed an overall of 88.1%. No significant relationship was noted between NLR, SII, and patients with comorbidities. Conclusion: The study highlights the diagnostic potential of SII and NLR in addition to hematologic markers in BP and PV, emphasizing their role in early diagnosis and therapeutic interventions, requiring further validation in larger patient cohorts.
文摘Pre-diabetic insulin resistance is associated with sub-clinical inflammation and concomitant increase in systemic C-reactive protein(CRP)levels.Type 2 diabetes mellitus(T2DM)patients register even higher chronic levels of inflammation,with excess circulating CRP originating from both typical hepatic synthesis,and also visceral white adipose tissue.
基金funded by National Natural Science Foundation of China(grant 82030071 and 82272495)Natural Science Foundation of Hunan Province(grant 2020JJ5930 and 2020JJ4874)the Science and Technology Major Project of Changsha(No.kh2103008).
文摘Cellular senescence assumes pivotal roles in various diseases through the secretion of proinflammatory factors.Despite extensive investigations into vascular senescence associated with aging and degenerative diseases,the molecular mechanisms governing microvascular endothelial cell senescence induced by traumatic stress,particularly its involvement in senescence-induced inflammation,remain insufficiently elucidated.In this study,we present a comprehensive demonstration and characterization of microvascular endothelial cell senescence induced by spinal cord injury(SCI).Lysine demethylase 6A(Kdm6a),commonly known as UTX,emerges as a crucial regulator of cell senescence in injured spinal cord microvascular endothelial cells(SCMECs).Upregulation of UTX induces senescence in SCMECs,leading to an amplified release of proinflammatory factors,specifically the senescenceassociated secretory phenotype(SASP)components,thereby modulating the inflammatory microenvironment.Conversely,the deletion of UTX in endothelial cells shields SCMECs against senescence,mitigates the release of proinflammatory SASP factors,and promotes neurological functional recovery after SCI.UTX forms an epigenetic regulatory axis by binding to calponin 1(CNN1),orchestrating trauma-induced SCMECs senescence and SASP secretion,thereby influencing neuroinflammation and neurological functional repair.Furthermore,local delivery of a senolytic drug reduces senescent SCMECs and suppresses proinflammatory SASP secretion,reinstating a local regenerative microenvironment and enhancing functional repair after SCI.In conclusion,targeting the UTX-CNN1 epigenetic axis to prevent trauma-induced SCMECs senescence holds the potential to inhibit SASP secretion,alleviate neuroinflammation,and provide a novel treatment strategy for SCI repair.
文摘BACKGROUND Studies have demonstrated the influence of immunity and inflammation on the development of tumors.Although single biomarkers of immunity and inflam-mation have been shown to be clinically predictive,the use of biomarkers integrating both to predict prognosis in patients with gastric cancer remains to be investigated.AIM To investigate the prognostic and clinical significance of inflammatory biomarkers and lymphocytes in patients undergoing surgical treatment for gastric cancer.METHODS Univariate COX regression analysis was performed to identify potential prognostic factors for patients with gastric cancer undergoing surgical treatment.Least absolute shrinkage and selection operator-COX(LASSO-COX)regression analysis was performed to integrate these factors and formulate a new prognostic immunoinflammatory index(PII).The correlation between PII and clinical charac-teristics was statistically analyzed.Nomograms incorporating the PII score were devised and validated based on the time-dependent area under the curve and decision curve analysis.RESULTS Patients exhibiting elevated neutrophil-to-lymphocyte ratio,platelet-to-lymphocyte ratio,and systemic immune inflammatory index displayed inferior progression-free survival(PFS)and overall survival(OS).Conversely,low levels of CD3(+),CD3(+)CD8(+),CD4(+)CD8(+),and CD3(+)CD16(+)CD56(+)T lymphocytes were associated with improved PFS and OS,while high CD19(+)T lymphocyte levels were linked to worse PFS and OS.The PII score demonstrated associations with tumor characteristics(primary tumor site and tumor size),establishing itself as an independent prognostic factor for both PFS and OS.Time-dependent area under the curve and decision curve analysis affirmed the effectiveness of the PII-based nomogram as a robust prognostic predictive model.CONCLUSION PII may be a reliable predictor of prognosis in patients with gastric cancer undergoing surgical treatment,and it offers insights into cancer-related immune-inflammatory responses,with potential significance in clinical practice.
基金This work was supported financially by Korea Environment Industry&Technology Institute through Project to make multi-ministerial national biological research resources more advanced program,funded by Korea Ministry of Environment(grant number RS-2023-00230403).
文摘Objective:To evaluate the effect of the ethyl acetate fraction derived from Sargassum pallidum extract against particulate matter(PM)-induced oxidative stress and inflammation in HaCaT cells and zebrafish.Methods:HaCaT cells and zebrafish were used to evaluate the protective effects of the ethyl acetate fraction of Sargassum pallidum extract against PM-induced oxidative stress and inflammation.The production of nitric oxide(NO),intracellular ROS,prostaglandin E_(2)(PGE_(2)),and pro-inflammatory cytokines,and the expression levels of COX-2,iNOS,and NF-κB were evaluated in PM-induced HaCaT cells.Furthermore,the levels of ROS,NO,and lipid peroxidation were assessed in the PM-exposed zebrafish model.Results:The ethyl acetate fraction of Sargassum pallidum extract significantly decreased the production of NO,intracellular ROS,and PGE_(2) in PM-induced HaCaT cells.In addition,the fraction markedly suppressed the levels of pro-inflammatory cytokines and inhibited the expression levels of COX-2,iNOS,and NF-κB.Furthermore,it displayed remarkable protective effects against PM-induced inflammatory response and oxidative stress,represented by the reduction of NO,ROS,and lipid peroxidation in zebrafish.Conclusions:The ethyl acetate fraction of Sargassum pallidum extract exhibits a protective effect against PM-induced oxidative stress and inflammation both in vitro and in vivo and has the potential as a candidate for the development of pharmaceutical and cosmeceutical products.
基金Supported by Chongqing Fundamental Research Funds,No.jbky20210001Key Programs of Technological Innovation and Application Development of Chongqing,China,No.cstc2021jscx-dxwtBX0016+2 种基金Natural Science Foundation of Chongqing,No.cstc2021jcyjmsxmX0793Science and Technology Project in Social Livelihood of Bishan District,Chongqing,China,No.BSKJ0078 and No.BSKJ0075Performance Incentive-oriented Project of Chongqing,No.jxjl20220007。
文摘BACKGROUND The modified Xiaoyao San(MXS)formula is an adjuvant drug recommended by the National Health Commission of China for the treatment of liver cancer,which has the effect of preventing postoperative recurrence and metastasis of hepatocellular carcinoma and prolonging patient survival.However,the molecular mechanisms underlying that remain unclear.AIM To investigate the role and mechanisms of MXS in ameliorating hepatic injury,steatosis and inflammation.METHODS A choline-deficient/high-fat diet-induced rat nonalcoholic steatohepatitis(NASH)model was used to examine the effects of MXS on lipid accumulation in primary hepatocytes.Liver tissues were collected for western blotting and immunohisto chemistry(IHC)assays.Lipid accumulation and hepatic fibrosis were detected using oil red staining and Sirius red staining.The serum samples were collected for biochemical assays and NMR-based metabonomics analysis.The inflammation/lipid metabolism-related signaling and regulators in liver tissues were also detected to reveal the molecular mechanisms of MXS against NASH.RESULTS MXS showed a significant decrease in lipid accumulation and inflammatory response in hepatocytes under metabolic stress.The western blotting and IHC results indicated that MXS activated AMPK pathway but inhibited the expression of key regulators related to lipid accumulation,inflammation and hepatic fibrosis in the pathogenesis of NASH.The metabonomics analysis systemically indicated that the arachidonic acid metabolism and steroid hormone synthesis are the two main target metabolic pathways for MXS to ameliorate liver inflammation and hepatic steatosis.Mechanistically,we found that MXS protected against NASH by attenuating the sex hormone-related metabolism,especially the metabolism of male hormones.CONCLUSION MXS ameliorates inflammation and hepatic steatosis of NASH by inhibiting the metabolism of male hormones.Targeting male hormone related metabolic pathways may be the potential therapeutic approach for NASH.
文摘Myeloproliferative neoplasms(MPN)are a group of diseases characterized by the clonal proliferation of hematopoietic progenitor or stem cells.They are clinically classifiable into four main diseases:chronic myeloid leukemia,essential thrombocythemia,polycythemia vera,and primary myelofibrosis.These pathologies are closely related to cardio-and cerebrovascular diseases due to the increased risk of arterial thrombosis,the most common underlying cause of acute myocardial infarction.Recent evidence shows that the classical Virchow triad(hypercoagulability,blood stasis,endothelial injury)might offer an explanation for such association.Indeed,patients with MPN might have a higher number and more reactive circulating platelets and leukocytes,a tendency toward blood stasis because of a high number of circulating red blood cells,endothelial injury or overactivation as a consequence of sustained inflammation caused by the neoplastic clonal cell.These abnormal cancer cells,especially when associated with the JAK2V617F mutation,tend to proliferate and secrete several inflammatory cytokines.This sustains a pro-inflammatory state throughout the body.The direct consequence is the induction of a pro-thrombotic state that acts as a determinant in favoring both venous and arterial thrombus formation.Clinically,MPN patients need to be carefully evaluated to be treated not only with cytoreductive treatments but also with cardiovascular protective strategies.
文摘Inflammation is a multifaceted cellular and molecular response triggered by injury,infection,or various pathological conditions.Serving as a protective defense mechanism,the inflammatory response involves clinical signs like redness,swelling,pain,and increased body temperature.Immune cells,notably neutrophils and macrophages,play key roles in orchestrating this response.The delicate balance between proinflammatory and anti-inflammatory mediators,including cytokines and chemokines,regulates the inflammatory cascade.While acute inflammation is crucial for tissue repair,chronic inflammation may indicate an imbalance,contributing to conditions like autoimmune diseases.Understanding these mechanisms is vital for developing therapeutic strategies and managing chronic diseases.
基金supported by the National Natural Science Foundation of China,Nos.82271327(to ZW),82072535(to ZW),81873768(to ZW),and 82001253(to TL).
文摘We previously showed that hydrogen sulfide(H2S)has a neuroprotective effect in the context of hypoxic ischemic brain injury in neonatal mice.However,the precise mechanism underlying the role of H2S in this situation remains unclear.In this study,we used a neonatal mouse model of hypoxic ischemic brain injury and a lipopolysaccharide-stimulated BV2 cell model and found that treatment with L-cysteine,a H2S precursor,attenuated the cerebral infarction and cerebral atrophy induced by hypoxia and ischemia and increased the expression of miR-9-5p and cystathionineβsynthase(a major H2S synthetase in the brain)in the prefrontal cortex.We also found that an miR-9-5p inhibitor blocked the expression of cystathionineβsynthase in the prefrontal cortex in mice with brain injury caused by hypoxia and ischemia.Furthermore,miR-9-5p overexpression increased cystathionine-β-synthase and H2S expression in the injured prefrontal cortex of mice with hypoxic ischemic brain injury.L-cysteine decreased the expression of CXCL11,an miR-9-5p target gene,in the prefrontal cortex of the mouse model and in lipopolysaccharide-stimulated BV-2 cells and increased the levels of proinflammatory cytokines BNIP3,FSTL1,SOCS2 and SOCS5,while treatment with an miR-9-5p inhibitor reversed these changes.These findings suggest that H2S can reduce neuroinflammation in a neonatal mouse model of hypoxic ischemic brain injury through regulating the miR-9-5p/CXCL11 axis and restoringβ-synthase expression,thereby playing a role in reducing neuroinflammation in hypoxic ischemic brain injury.
文摘In neurodegenerative and classically demyelinating disorders such as multiple sclerosis(MS),spinal cord injury(SCI),stroke,and Charcot-Marie-Tooth disease,glial functioning is compromised and nervous tissue integrity is lost.Recently,primary neurodegenerative disorders such as Alzheimer’s disease,amyotrophic lateral sclerosis(ALS),and Parkinson’s disease(PD)are increasingly linked to impaired oligodendroglia functioning upon neurodegeneration.Due to the destructive micro-environment created by nervous tissue damage,the progressive cellular loss in these disorders,and the amitotic nature of neurons,spontaneous endogenous repair process are limited in nature.Hence,there is a medical need for efficient therapeutic strategies capable of supporting neuro-reparative processes to occur,likely supported by improved oligodendroglia cell functioning.
基金funded by Portuguese funds through FCT——Funda??o para a Ciência e a Tecnologia/Ministério da Ciência,Tecnologia e Ensino Superior in the framework of the project PTDC/MEDNEU/1677/2021(to JBR)。
文摘Neuroimmunology is emerging as a pivotal field,shedding light on the intricate dialogues between the central nervous system(CNS)and the immune system.This exploration is particularly significant in understanding microglia,the CNS’s innate immune cells,beyond the conventional conflation of“neuroinflammation”and“microglial activation.”This conflation has clouded the true complexity of these processes,potentially stalling scientific progress and the development of new therapies.We challenge the long-standing perspectives that have oversimplified these interactions,advocating for a deeper exploration of the dynamic relationship between neuroinflammation and microglial activation.By dissecting specific molecular pathways,we aim to illuminate their elaborate roles in neuroinflammatory responses,especially in the context of Alzheimer’s disease(AD).Here,neuroinflammation is not merely a passive observer or a direct antagonist but a complex agent in the disease’s progression.This article calls for a significant paradigm shift towards an integrative,multi-omics approach to neuroimmunology.Adopting such a comprehensive framework is crucial for advancing our understanding of neuroinflammatory conditions and paving the way for targeted therapeutic strategies for brain diseases.
文摘Brain organoids mimic closely the embryonic human brain:Over the last decade,the development of human organoid systems has evolved rapidly.Different tissues have been modeled with organoids,such as the gut,lung,liver,kidney retina and brain.These systems have a high cellular heterogeneity,with many cell types integrated into the same system.Organoids'cellular populations interact between and amongst each other in a cellular and molecular level,which represents an advantage with respects to monolayer 2D cell culture systems.
基金the National Institutes of Health(NIH–National Institute of Dental and Craniofacial Research,grant R01DE031476)。
文摘Apical periodontitis(AP)is a dental-driven condition caused by pathogens and their toxins infecting the inner portion of the tooth(i.e.,dental pulp tissue),resulting in inflammation and apical bone resorption affecting 50%of the worldwide population,with more than 15 million root canals performed annually in the United States.Current treatment involves cleaning and decontaminating the infected tissue with chemo-mechanical approaches and materials introduced years ago,such as calcium hydroxide,zinc oxide–eugenol,or even formalin products.Here,we present,for the first time,a nanotherapeutics based on using synthetic highdensity lipoprotein(sHDL)as an innovative and safe strategy to manage dental bone inflammation.sHDL application in concentrations ranging from 25μg to 100μg/mL decreases nuclear factor Kappa B(NF-κB)activation promoted by an inflammatory stimulus(lipopolysaccharide,LPS).Moreover,sHDL at 500μg/mL concentration markedly decreases in vitro osteoclastogenesis(P<0.001),and inhibits IL-1α(P=0.027),TNF-α(P=0.004),and IL-6(P<0.001)production in an inflammatory state.Notably,sHDL strongly dampens the Toll-Like Receptor signaling pathway facing LPS stimulation,mainly by downregulating at least 3-fold the pro-inflammatory genes,such as Il1b,Il1a,Il6,Ptgs2,and Tnf.In vivo,the lipoprotein nanoparticle applied after NaOCl reduced bone resorption volume to(1.3±0.05)mm^(3) and attenuated the inflammatory reaction after treatment to(1090±184)cells compared to non-treated animals that had(2.9±0.6)mm^(3)(P=0.0123)and(2443±931)cells(P=0.004),thus highlighting its promising clinical potential as an alternative therapeutic for managing dental bone inflammation.
基金supported by the grants from the Natural Science Foundation of Beijing Municipality(Grant No.:7212185)the Scientific and Technological Innovation project of China Academy of Chinese Medical Sciences(Grant No.:CI2021A03808)+3 种基金the National Natural Science Foundation of China(Grant Nos.:82330124,81974526,and 82274176)the Innovation Team and Talents Cultivation Program of the National Administration of Traditional Chinese Medicine,China(Program No.:ZYYCXTD-C-202002)the Special Project for Training Outstanding Young Scientific and Technological Talents(innovative type)of Necessary Scientific Research Business Expenses of China Academy of Chinese Medical Sciences(Project Nos.:ZZ13-YQ-051,and ZZ15-YQ-063)the Fundamental Research Funds for the Central public welfare research institutes(Grant No.:ZXKT21010).
文摘Nowadays,roughly 603.7 million people are bothered by obesity[1].More seriously,obesity brings inflammation to the peripheral and central nervous system,which compromises the comorbidity of obesity,major depression[2],and cognitive deficits[3].Drug competent in the comorbidity is still lacking.In 2015,Liu et al.[4]reported celastrol(CEL)as a powerful anti-obesity agent.In our previous study.
文摘In 1872, George Huntington presented his essay “On Chorea” to the Meigs and Mason Academy of Medicine and, in doing so, detailed a disease that would later bear his name. Huntington's disease(HD) is a genetic, neurodegenerative disease that manifests as the loss of motor control,cognitive impairment,and mood and psychiatric changes in paents.
基金supported by NIH funding(RF1NS110637,2RF1NS094527,R01NS110635)to JW.
文摘Traumatic spinal cord injury(SCI)is a devastating exogenous injury with long-lasting consequences and a leading cause of death and disability worldwide.Advances in assistive technology,rehabilitative interventions,and the ability to identify and intervene in secondary conditions have significantly increased the long-term survival rate of SCI patients,with some people even living well into their seventh or eighth decade.These survival changes have led neurotrauma researchers to examine how SCI interacts with brain aging.Public health and epidemiological data showed that patients with long-term SCI can have a lower life expectancy and quality of life,along with a higher risk of comorbidities and complications.
基金supported by the Christiane and Claudia Hempel Foundation for Regenerative Medicineby the James and Elisabeth Cloppenburg, Peek and Cloppenburg Düsseldorf Stiftung(to PK)。
文摘Introduction to human endogenous retrovirus type-W(HERV-W): Genomic inheritance from the past includes retroviral sequences that have been stably incorporated into our genomes and account for up to 8% of human DNA.
文摘In the article entitled“Boeravinone B ameliorates allergic nasal inflammation by modulating the GATA-3/T-bet signaling pathway in a mouse model of allergic rhinitis”,published on pages 245-252,Issue 6,Volume 14 in Asian Pacific Journal of Tropical Biomedicine,the weight number was misspelled as“18.5 g”on page 246,first line,under 2.2.Animals paragraph.The correct weight should be“(18.5±5)g”.
基金supported by JSPS KAKENHI(JP23K14675)PRIN 2022(202238WEHT)(to DC)。
文摘Aging is associated with chronic form of inflammation called inflammaging,which results from immune system changes.Inflammaging plays a crucial role in the pathogenesis of various neurodegenerative diseases(Dabravolski et al.,2022).Moreove r,aging-related inflammation can be triggered by disrupted mitophagy.
