Since it was first reported in December 2019,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has spread rapidly around the world to cause the ongoing pandemic.Although the clinical manifestations ...Since it was first reported in December 2019,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has spread rapidly around the world to cause the ongoing pandemic.Although the clinical manifestations of SARS-CoV-2 infection are predominantly in the respiratory system,liver enzyme abnormalities exist in around half of the cases,which indicate liver injury,and raise clinical concern.At present,there is no consensus whether the liver injury is directly caused by viral replication in the liver tissue or indirectly by the systemic inflammatory response.This review aims to summarize the clinical manifestations and to explore the underlying mechanisms of liver dysfunction in patients with SARSCoV-2 infection.展开更多
Dysregulated pseudo-hypoxia （through its effects on cell survival, angiogenesis, metabolism, invasion） and epigenetic dysregulation [through widespread suppression of tumor suppressor genes involved in cell cycle, a...Dysregulated pseudo-hypoxia （through its effects on cell survival, angiogenesis, metabolism, invasion） and epigenetic dysregulation [through widespread suppression of tumor suppressor genes involved in cell cycle, apoptosis, adhesion, immune evasion, etc. （1）] are considered to be the two central driving pathogenic features in the progression of clear cell Renal Cell Carcinoma （ccRCC） （2,3）.展开更多
BACKGROUND Organ transplantation has emerged as a globally prevalent therapeutic modality for end-stage organ failure,yet the post-transplantation trajectory is increasingly complicated by a spectrum of metabolic sequ...BACKGROUND Organ transplantation has emerged as a globally prevalent therapeutic modality for end-stage organ failure,yet the post-transplantation trajectory is increasingly complicated by a spectrum of metabolic sequelae,with obesity emerging as a critical clinical challenge.AIM To systematically review the multifactorial mechanisms underlying obesity following organ transplantation and to integrate evidence from pharmacological,behavioral,and molecular perspectives,thereby providing a foundation for targeted interventions.METHODS We conducted a systematic search in PubMed and Web of Science for literature published from 2020 to 15 July 2025.The search strategy incorporated terms including“obesity”,“overweight”and“post organ transplantation”.Only randomized controlled trials,meta-analyses,and systematic reviews were included.Non-empirical publications and irrelevant studies were excluded.Data extraction and quality assessment were performed by two independent reviewers,with disagreements resolved by a third researcher.RESULTS A total of 1457 articles were initially identified,of which 146 met the inclusion criteria.These studies encompassed liver,kidney,heart,and lung transplant recipients.Key findings indicate that immunosuppressive drugs-especially corticosteroids and calcineurin inhibitors-promote hyperphagia,insulin resistance,and dyslipidemia.Post-transplant sedentary behavior and hypercaloric diets further contribute to positive energy balance.At the molecular level,immunosuppressants disrupt adipokine signaling(e.g.,leptin and adiponectin),induce inflammatory and oxidative stress responses,and activate adipogenic pathways leading to lipid accumulation.CONCLUSION Post-transplant obesity arises from a complex interplay of pharmacological,behavioral,and molecular factors.A multidisciplinary approach-incorporating pharmacological modification,nutritional management,physical activity,and molecular-targeted therapies-is essential to mitigate obesity and improve transplant outcomes.Further large-scale and mechanistic studies are warranted to establish evidence-based preventive and treatment strategies.展开更多
With the industrialization of agriculture and the advancement of medical care,human life expectancy has increased considerably and continues to rise steadily.This results in novel and unprecedented challenges,namely o...With the industrialization of agriculture and the advancement of medical care,human life expectancy has increased considerably and continues to rise steadily.This results in novel and unprecedented challenges,namely obesity and neurodegeneration.展开更多
Calcium (Ca^(2+)) is a key intracellular messenger involved in a variety of cellular functions.Intracellular Ca^(2+)dysregulation drives neuron cell death in multiple degenerative diseases and traumatic conditions.Ret...Calcium (Ca^(2+)) is a key intracellular messenger involved in a variety of cellular functions.Intracellular Ca^(2+)dysregulation drives neuron cell death in multiple degenerative diseases and traumatic conditions.Retinal ganglion cell(RGC) degeneration occurs in blinding diseases such as glaucoma and other optic neuropathies.展开更多
BACKGROUND Complement-mediated thrombotic microangiopathy(TMA)is a rare endothelial injury syndrome caused by dysregulated activation of the alternative complement pathway,often linked to genetic abnormalities in comp...BACKGROUND Complement-mediated thrombotic microangiopathy(TMA)is a rare endothelial injury syndrome caused by dysregulated activation of the alternative complement pathway,often linked to genetic abnormalities in complement factor H(CFH),complement factor I,or complement factor H-related(CFHR)proteins.Both renal transplantation and pregnancy are independent triggers for recurrence.This case highlights a genetically high-risk patient who achieved a successful term pregnancy after renal transplantation without complement inhibition,emphasizing individualized risk stratification,close surveillance,and multidisciplinary management for favourable maternal and graft outcomes.CASE SUMMARY A 32-year-old woman with end-stage renal disease secondary to genetically confirmed complement-mediated TMA—homozygous CFH exon 17 deletion and CFHR3-CFHR1 duplication—was maintained on dialysis for 2.5 years before undergoing a successful live-donor kidney transplant from her mother.Post-transplant immunosuppression included tacrolimus,mycophenolate mofetil,and prednisolone,later modified to azathioprine during pregnancy planning.One-year post-transplant,she conceived spontaneously.Pregnancy was complicated by transient gestational hypertension,controlled with nifedipine,labetalol,and amlodipine.Proteinuria remained<150 mg/day;white blood cell counts 5.8-7.2×109/L without cytopenia.Serum creatinine ranged 0.9-1.1 mg/dL,and tacrolimus trough levels 5-7 ng/mL.At 36 weeks,she delivered a healthy 3 kg infant by elective caesarean section.Postpartum follow-up at three months confirmed stable maternal and graft function.CONCLUSION High-risk complement-mediated TMA patients can achieve successful pregnancy post-transplant through individualized care without mandatory complement blockade.展开更多
Immune dysregulation diseases are characterized by heterogeneous clinical manifestations and may have severe disease courses.The identification of the genetic causes of these diseases therefore has critical clinical i...Immune dysregulation diseases are characterized by heterogeneous clinical manifestations and may have severe disease courses.The identification of the genetic causes of these diseases therefore has critical clinical implications.We performed whole-exome sequencing of patients with immune dysregulation disorders and identified two patients with previously undescribed mutations in LRRC32,which encodes glycoprotein A repetitions predominant(GARP).These patients were characterized by markedly reduced numbers and frequencies of regulatory T cells(Tregs).Tregs with mutated LRRC32 exhibited strongly diminished cell-surface GARP expression and reduced suppressor function.In a model of conditional Garp deficiency in mice,we confirmed increased susceptibility to inflammatory diseases once GARP expression on Tregs was decreased.Garp deficiency led to an unstable Treg phenotype due to diminished Foxp3 protein acetylation and stability.Our study reinforces the understanding of the immunological mechanisms of immune dysregulation and expands the knowledge on the immunological function of GARP as an important regulator of Treg stability.展开更多
Exertional heat stroke (EHS) is a life-threatening condition characterized by profound central nervous system (CNS)dysfunction and core temperature typically>40°C.^([1])This condition involves complex pathophy...Exertional heat stroke (EHS) is a life-threatening condition characterized by profound central nervous system (CNS)dysfunction and core temperature typically>40°C.^([1])This condition involves complex pathophysiological processes in which heat triggers a cascade of dysregulated inflammatory responses,endothelial dysfunction,coagulation abnormalities,and muscle damage.These processes can lead to multiorgan failure,significantly increasing the risk of mortality.^([2])Given the severity of EHS,early identification and timely intervention are crucial.However,there are no specific diagnostic markers for EHS,^([1])highlighting the need to identify reliable clinical parameters that can assist early decision-making.展开更多
Inflammatory bowel disease(IBD)comprises a heterogeneous group of chronic inflammatory conditions of the intestine.Current therapeutic strategies primarily focus on maintaining remission and mitigating the secondary e...Inflammatory bowel disease(IBD)comprises a heterogeneous group of chronic inflammatory conditions of the intestine.Current therapeutic strategies primarily focus on maintaining remission and mitigating the secondary effects rather than reversing its pathogenic mechanisms(Jeong et al.,2019).The pathogenesis of IBD involves intestinal barrier dysfunction,tissue damage,and dysregulated innate and adaptive immune responses(de Souza et al.,2017).Elevated neutrophil activity has been reported in IBD(Danne et al.,2024),yet the precise roles and mechanisms of neutrophils in disease progression remain to be elucidated.展开更多
The rapid expansion of urbanization has led to widespread exposure of wild birds to intensive light at night(LAN).While previous studies have established LAN-induced cognitive impairment in birds,the underlying neurob...The rapid expansion of urbanization has led to widespread exposure of wild birds to intensive light at night(LAN).While previous studies have established LAN-induced cognitive impairment in birds,the underlying neurobiological mechanisms remain poorly understood.We hypothesized that LAN exposure impaired cognitive function of birds potentially through neurodegeneration,metabolic dysregulation and neuroinflammatory responses in the telencephalon.Using Zebra Finches(Taeniopygia guttata)as an avian model,under 16L:8D photoperiods,we compared associative learning and memory abilities and neurobiological parameters between experimental groups exposed to dim light at night(LAN)versus nocturnal darkness(CTR).Compared to the CTR birds,the LAN-exposed birds exhibited significantly lower learning and memory performances,reduced neuron density and simplified dendritic morphology in the telencephalons.The key energy metabolic substrates(cholic acid,CTP,D-mannose-6-phosphate)and neuroprotective agents(trehalose,menaquinone,L-gulono-1,4-lactone)in the telencephalons of LAN-exposed birds showed depletion,while oxidative stress markers(methionine sulfoxide)and inflammatory mediators(cis-gondoic acid)exhibited elevation.The neurotransmitter dopamine and histamine metabolic pathway were disrupted in the LAN-exposed birds.The microglias were activated with pro-inflammatory IL-1βand IL-6 levels increasing and anti-inflammatory IL-10 decreasing in the telencephalons of the LAN-exposed birds.These findings indicate a potential mechanistic pathway whereby dim light exposure at night can induce neuroinflammation through oxidative stress-mediated microglial activation,energy metabolism and neurotransmitter homeostasis disruption,ultimately leading to neurodegeneration in the telencephalons of birds.展开更多
BACKGROUND Synthetic messenger RNA(mRNA)vaccines have raised concerns regarding prolonged spike protein expression,immune activation,and potential off-target effects.AIM To investigate transcriptomic alterations in in...BACKGROUND Synthetic messenger RNA(mRNA)vaccines have raised concerns regarding prolonged spike protein expression,immune activation,and potential off-target effects.AIM To investigate transcriptomic alterations in individuals with new-onset adverse events or cancer following mRNA coronavirus disease 2019 vaccination.METHODS Bulk RNA sequencing was performed on peripheral blood from two patient groups:(1)Individuals with new-onset nonmalignant adverse events;and(2)Individuals newly diagnosed with cancer post-vaccination.A control group of normal individuals was used for comparison.Differential gene expression was analyzed using DESeq2,and Gene Set Enrichment Analysis was conducted using the MSigDB database and custom gene sets.RESULTS Both vaccine patient groups displayed widespread transcriptional dysregulation.In the nonmalignant adverse event group,hallmark enrichments included mitochondrial dysfunction,proteasome-mediated stress,transcriptomic instability,and systemic inflammation.The cancer group exhibited additional hallmarks of genomic instability and epigenetic reprogramming.Nonsense-mediated decay,ribosomal stress,and myelocytomatosis oncogene activation were prominent in both groups,while immune signaling via toll-like receptors and type I interferons was particularly elevated in cancer patients.The observed transcriptomic profiles indicate cellular stress responses,mitochondrial dysfunction,and immune dysregulation following exposure to mRNA vaccines,potentially in susceptible individuals.CONCLUSION Shared and distinct molecular signatures in both cohorts demonstrate underlying mechanisms contributing to postvaccine symptomatology and complications,including oncogenesis and or progression of malignant disease.These findings underscore the need for a deeper investigation into the long-term safety of mRNA vaccines and host response variability.展开更多
BACKGROUND Pituitary macroadenomas represent a significant challenge in clinical management due to their variable presentations and complex treatment considerations.This manuscript explores the multidisciplinary appro...BACKGROUND Pituitary macroadenomas represent a significant challenge in clinical management due to their variable presentations and complex treatment considerations.This manuscript explores the multidisciplinary approach to understanding and managing pituitary macroadenomas,integrating neurosurgery,endocrinology,radiology,and pathology perspectives.AIM To summarize the literature on pituitary macroadenoma and outline the possible multidisciplinary approach in the diagnosis,management,and rehabilitation of individuals with pituitary adenomas,to add to already preexisting knowledge,in managing these cases enhancing better ocular and systemic outcomes.METHODS A search was conducted on an online publication database(PubMed)using the term“pituitary adenoma”including all results published over twenty years(2004-2024).Results were sorted for relevance,language,and completeness.RESULTS A total of 176 records were returned.The guidelines of the PRISMA 2020 statement were followed in this study.A total of 23 records were excluded due to being out of scope while a further 13 records were duplicates.Another 17 records were not available as full-length articles and were also excluded.The references of each included record was further searched for relevant publications.A total of 141 records were therefore used in this minireview.CONCLUSION Pituitary macroadenomas pose substantial clinical challenges due to their size and potential for significant hormonal and neurological impact,modern therapeutic strategies offer effective management options.Early detection and comprehensive treatment are essential for optimizing patient outcomes and maintaining quality of life.Continued research and advancements in medical technology are likely to further enhance the management and prognosis of this condition in the future.展开更多
Cancer,a leading cause of global mortality,remains a significant challenge to increasing life expectancy worldwide.Forkhead Box R2(FOXR2),identified as an oncogene within the FOX gene family,plays a crucial role in de...Cancer,a leading cause of global mortality,remains a significant challenge to increasing life expectancy worldwide.Forkhead Box R2(FOXR2),identified as an oncogene within the FOX gene family,plays a crucial role in developing various endoderm-derived organs.Recent studies have elucidated FOXR2-related pathways and their involvement in both tumor and non-tumor diseases.Dysregulation of FOXR2 has been linked to numerous malignant tumors,spanning the brain,nervous system,thyroid,osteosarcoma,Hodgkin lymphoma,colorectal,liver,pancreatic,lung,breast,ovarian,prostate,female genital tract,endometrial,and uterine cancers.Despite extensive research on FOXR2 dysregulation,its practical applications remain underexplored.This review delves into the mechanisms underlying FOXR2 dysregulation during oncogenesis and its implications for cancer diagnosis,prognosis,and treatment.展开更多
Schizophrenia is a multifaceted neurodevelopmental disorder characterized by hallucinations,delusions,cognitive deficits,and emotional dysregulation.The prefrontal cortex(PFC),essential for executive functions,working...Schizophrenia is a multifaceted neurodevelopmental disorder characterized by hallucinations,delusions,cognitive deficits,and emotional dysregulation.The prefrontal cortex(PFC),essential for executive functions,working memory,and emotional regulation,is notably impaired in this condition.This review consolidates current insights into the role of PFC dysfunction in schizophrenia,with a focus on its implications for therapeutic strategies.The neuroanatomical and neurobiological foundations of PFC dysfunction are explored,emphasizing structural abnormalities,functional dysconnectivity,and microcircuit disruptions that contribute to cognitive deficits and impaired decision-making.Clinical implications are discussed,particularly the correlation between PFC dysfunction and the severity and progression of schizophrenia symptoms.Additionally,pharmacological and non-pharmacological approaches aimed at modulating PFC activity are reviewed as potential therapeutic options.In conclusion,a deeper understanding of PFC dysfunction is pivotal for developing targeted treatments,and ongoing research offers promising avenues for enhancing outcomes for individuals affected by this debilitating disorder.展开更多
Emerging evidence indicates that childhood stressors, such as familial conflict, bullying, academic pressure, and traumatic events, can significantly worsen inflammatory skin conditions like atopic dermatitis (AD) and...Emerging evidence indicates that childhood stressors, such as familial conflict, bullying, academic pressure, and traumatic events, can significantly worsen inflammatory skin conditions like atopic dermatitis (AD) and psoriasis. This review explores the underlying neuroimmune pathways that link stress to skin inflammation in children, focusing on the role of the hypothalamic-pituitary-adrenal (HPA) axis and stress-induced cytokine production. Studies have shown that chronic psychological stress leads to dysregulation of the HPA axis, resulting in elevated cortisol levels, which paradoxically impair skin barrier function and upregulate pro-inflammatory cytokines such as IL-6, TNF-α, and IL-1β. Specific stressors, such as bullying, have been associated with heightened immune responses, increasing inflammation in the skin. For example, research has demonstrated that children who experience social stressors show elevated levels of C-reactive protein (CRP) and other markers of systemic inflammation, which directly correlate with skin condition flare-ups. Furthermore, exposure to early life stress has been linked to long-term alterations in immune function, perpetuating chronic inflammation even in the absence of ongoing stress. Future research should focus on longitudinal studies assessing how the timing, duration, and type of stressors influence skin condition severity, alongside evaluating interventions like cognitive-behavioral therapy (CBT) and stress management techniques. By addressing these childhood stressors, there is potential to not only mitigate skin condition flares but also reduce the long-term health consequences of chronic inflammation leading to therapeutic strategies that emphasize mental health alongside traditional dermatological treatments.展开更多
Hepatitis C virus(HCV)infection has been increasingly associated with cardio-vascular complications,particularly atherosclerosis and cardiomyopathy,in addition to its primary hepatic effects.Studies indicate a higher ...Hepatitis C virus(HCV)infection has been increasingly associated with cardio-vascular complications,particularly atherosclerosis and cardiomyopathy,in addition to its primary hepatic effects.Studies indicate a higher prevalence of carotid atherosclerosis in patients with chronic hepatitis C infection,with viral load and steatosis emerging as independent risk factors.HCV-related athero-sclerosis appears to develop through complex processes involving endothelial dysfunction,inflammation,oxidative stress,and immune dysregulation.Key cytokines,including tumor necrosis factor-alpha and interleukin-6,increase inflammatory responses,while oxidative stress markers,such as malondial-dehyde,are associated with an increased risk of atherogenesis.In addition,HCV infection has been linked to cardiomyopathy.Direct viral effects,including HCV replication within cardiomyocytes and cytotoxicity induced by viral proteins,lead to myocardial injury and functional decline.Indirectly,HCV triggers immune-mediated damage,with heightened pro-inflammatory cytokines exacerbating cardiomyocyte apoptosis and fibrosis.Furthermore,HCV infection promotes a procoagulant imbalance,as evidenced by elevated factor VIII levels and thrombin potential,contributing to the increased cardiovascular risk.While substantial evidence indicates a relationship between HCV and cardiovascular disease,further research is needed to establish causality and guide therapeutic interventions.展开更多
Functional gastrointestinal disorders,now termed“disorders of gut-brain interaction”(DGBI),are characterized by a spectrum of chronic gastrointestinal symptoms driven by dysregulated gut-brain interaction.DGBIs freq...Functional gastrointestinal disorders,now termed“disorders of gut-brain interaction”(DGBI),are characterized by a spectrum of chronic gastrointestinal symptoms driven by dysregulated gut-brain interaction.DGBIs frequently coexist with liver diseases,including cirrhosis,thereby exacerbating clinical manifestations and complicating management;this overlap is underpinned by shared mechanisms,including gut dysbiosis,increased intestinal permeability,systemic inflammation,and altered neuroimmune signaling.Portal hypertension in cirrhosis promotes small intestinal bacterial overgrowth and microbial translocation,thereby triggering inflammatory pathways that worsen gut and liver function.This minireview explores the gut-liver axis as a central mediator in the interplay between DGBIs and liver disease/cirrhosis.Clinically,these interactions manifest as refractory gastrointestinal symptoms,nutritional deficiencies,and impaired quality of life.Emerging research emphasizes the need for integrative diagnostic approaches,such as combining advanced imaging,microbiome analysis,and biomarker profiling,to unravel the complex interplay between DGBIs and liver disease/cirrhosis.Therapeutic interventions targeting the gut microbiome,neuroimmune pathways,and lifestyle modification can mitigate disease burden.This review underscores the importance of a multidisciplinary framework for enhancing patient outcomes and guiding future research in this intersectional field.展开更多
Objective:The etiology and pathogenesis of recurrent implantation failure(RIF)remain unclear.This study aimed to delineate the immune landscape and identify the pivotal biomarkers of immune dysregulation in RIF.Method...Objective:The etiology and pathogenesis of recurrent implantation failure(RIF)remain unclear.This study aimed to delineate the immune landscape and identify the pivotal biomarkers of immune dysregulation in RIF.Methods:Comprehensive bioinformatics analyses,including differential expression,functional enrichment,gene set enrichment,weighted gene co-expression network analysis,protein-protein interaction network,and machine learning analyses,were conducted to explore the immunological underpinnings of RIF.Results:Our findings demonstrated a significant downregulation in the expression of several immune-related gene sets in the RIF cohort,including those related to antigen processing and presentation,antimicrobial responses,chemokines and their receptors,cytokines,and natural killer cell cytotoxicity.These results provide evidence of a significant association between RIF and maternal-fetal immune dysregulation.Three signature genes(ANK3,PTGS2,andSLC39A2)were identified using various machine-learning methods.The diagnostic value and immunological relevance of these genes were confirmed in both discovery and validation cohorts.Conclusion:This study investigated the immune landscape of RIF using extensive bioinformatic analyses.Modular genes associated with both immune activity and RIF dysregulation were identified,providing new perspectives for understanding the pathophysiology and treatment of RIF.展开更多
BACKGROUND Gestational diabetes mellitus(GDM)has recently been associated with abnormal profiles of inflammatory cells and cytokines,though the findings remain incon-sistent and unclear.AIM To elucidate the peripheral...BACKGROUND Gestational diabetes mellitus(GDM)has recently been associated with abnormal profiles of inflammatory cells and cytokines,though the findings remain incon-sistent and unclear.AIM To elucidate the peripheral immune status in GDM.METHODS We systematically screened databases including Web of Science,PubMed,and EMBASE for eligible studies.Original articles reporting different immune cell levels in GDM compared to normal glucose-tolerance pregnant women were included to extract usable data.The pooled mean difference(MD)with 95%confidence interval(CI)was analyzed as the outcome measure.The Newcastle-Ottawa scale was employed to assess study quality.RESULTS A total of 19 studies involving various immune cell subgroups were included in our analysis.Specifically,total CD4+T cells(WMD=3.08;95%CI:0.81-5.35)were significantly increased in GDM groups.In contrast,total lymphocytes(SMD=0.05;95%CI:-0.16 to 0.26),CD3+T cells(SMD=-0.34;95%CI:-1.01 to 0.32),CD8+T cells(SMD=0.21;95%CI:-0.31 to 0.73),and natural killer T(NKT)Cells(SMD=0.83;95%CI:-1.10 to 2.75)showed no significant changes in GDM.Activation markers(HLA-DR+or CD69+)on CD4+T cells(WMD=0.20;95%CI:0.06-0.34)were increased in GDM patients.Treg cells,a classical subgroup of CD4+T cells,showed a decreasing trend in GDM compared to controls(SMD=-0.83;95%CI:-1.31 to-0.34).These results indicate an abnormal immune status in the peripheral profiles of GDM.CONCLUSION GDM may not only be a dysglycemia-related condition but also an immune disorder characterized by abnormal peripheral immune profiles,including higher levels of CD4+T cells and a reduced population of Treg cells.Tr-eating immune dysregulation could be a new direction for GDM management,although further research is needed to understand the precise mechanisms of immune overactivation in GDM.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
基金Supported by Sino-German Center for Research Promotion,National Natural Science Foundation of China,No.C-0029Health Commission of Chengdu,No.2020179.
文摘Since it was first reported in December 2019,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has spread rapidly around the world to cause the ongoing pandemic.Although the clinical manifestations of SARS-CoV-2 infection are predominantly in the respiratory system,liver enzyme abnormalities exist in around half of the cases,which indicate liver injury,and raise clinical concern.At present,there is no consensus whether the liver injury is directly caused by viral replication in the liver tissue or indirectly by the systemic inflammatory response.This review aims to summarize the clinical manifestations and to explore the underlying mechanisms of liver dysfunction in patients with SARSCoV-2 infection.
文摘Dysregulated pseudo-hypoxia （through its effects on cell survival, angiogenesis, metabolism, invasion） and epigenetic dysregulation [through widespread suppression of tumor suppressor genes involved in cell cycle, apoptosis, adhesion, immune evasion, etc. （1）] are considered to be the two central driving pathogenic features in the progression of clear cell Renal Cell Carcinoma （ccRCC） （2,3）.
基金Supported by the National Natural Science Foundation of China,No.82305376the Youth Talent Support Project of the China Acupuncture and Moxibustion Association,No.2024-2026ZGZJXH-QNRC005+2 种基金the 2024 Jiangsu Province Youth Science and Technology Talent Support Project,No.JSTJ-2024-3802025 Jiangsu Provincial Science and Technology Think Tank Program Project,No.JSKX0125035and 2025 College Student Innovation Training Program Project,No.X202510315373。
文摘BACKGROUND Organ transplantation has emerged as a globally prevalent therapeutic modality for end-stage organ failure,yet the post-transplantation trajectory is increasingly complicated by a spectrum of metabolic sequelae,with obesity emerging as a critical clinical challenge.AIM To systematically review the multifactorial mechanisms underlying obesity following organ transplantation and to integrate evidence from pharmacological,behavioral,and molecular perspectives,thereby providing a foundation for targeted interventions.METHODS We conducted a systematic search in PubMed and Web of Science for literature published from 2020 to 15 July 2025.The search strategy incorporated terms including“obesity”,“overweight”and“post organ transplantation”.Only randomized controlled trials,meta-analyses,and systematic reviews were included.Non-empirical publications and irrelevant studies were excluded.Data extraction and quality assessment were performed by two independent reviewers,with disagreements resolved by a third researcher.RESULTS A total of 1457 articles were initially identified,of which 146 met the inclusion criteria.These studies encompassed liver,kidney,heart,and lung transplant recipients.Key findings indicate that immunosuppressive drugs-especially corticosteroids and calcineurin inhibitors-promote hyperphagia,insulin resistance,and dyslipidemia.Post-transplant sedentary behavior and hypercaloric diets further contribute to positive energy balance.At the molecular level,immunosuppressants disrupt adipokine signaling(e.g.,leptin and adiponectin),induce inflammatory and oxidative stress responses,and activate adipogenic pathways leading to lipid accumulation.CONCLUSION Post-transplant obesity arises from a complex interplay of pharmacological,behavioral,and molecular factors.A multidisciplinary approach-incorporating pharmacological modification,nutritional management,physical activity,and molecular-targeted therapies-is essential to mitigate obesity and improve transplant outcomes.Further large-scale and mechanistic studies are warranted to establish evidence-based preventive and treatment strategies.
文摘With the industrialization of agriculture and the advancement of medical care,human life expectancy has increased considerably and continues to rise steadily.This results in novel and unprecedented challenges,namely obesity and neurodegeneration.
文摘Calcium (Ca^(2+)) is a key intracellular messenger involved in a variety of cellular functions.Intracellular Ca^(2+)dysregulation drives neuron cell death in multiple degenerative diseases and traumatic conditions.Retinal ganglion cell(RGC) degeneration occurs in blinding diseases such as glaucoma and other optic neuropathies.
文摘BACKGROUND Complement-mediated thrombotic microangiopathy(TMA)is a rare endothelial injury syndrome caused by dysregulated activation of the alternative complement pathway,often linked to genetic abnormalities in complement factor H(CFH),complement factor I,or complement factor H-related(CFHR)proteins.Both renal transplantation and pregnancy are independent triggers for recurrence.This case highlights a genetically high-risk patient who achieved a successful term pregnancy after renal transplantation without complement inhibition,emphasizing individualized risk stratification,close surveillance,and multidisciplinary management for favourable maternal and graft outcomes.CASE SUMMARY A 32-year-old woman with end-stage renal disease secondary to genetically confirmed complement-mediated TMA—homozygous CFH exon 17 deletion and CFHR3-CFHR1 duplication—was maintained on dialysis for 2.5 years before undergoing a successful live-donor kidney transplant from her mother.Post-transplant immunosuppression included tacrolimus,mycophenolate mofetil,and prednisolone,later modified to azathioprine during pregnancy planning.One-year post-transplant,she conceived spontaneously.Pregnancy was complicated by transient gestational hypertension,controlled with nifedipine,labetalol,and amlodipine.Proteinuria remained<150 mg/day;white blood cell counts 5.8-7.2×109/L without cytopenia.Serum creatinine ranged 0.9-1.1 mg/dL,and tacrolimus trough levels 5-7 ng/mL.At 36 weeks,she delivered a healthy 3 kg infant by elective caesarean section.Postpartum follow-up at three months confirmed stable maternal and graft function.CONCLUSION High-risk complement-mediated TMA patients can achieve successful pregnancy post-transplant through individualized care without mandatory complement blockade.
基金supported by the Deutsche Forschungsgemeinschaft,grants SK59/4-1,SK59/9-1,Schu 786/8-1,and Schu 1683/10-1by the Verbundantrage"ArthroMark"(projects 1 and 7,OIEC100913),"lmpam"(project 10,OIEC1008H),and"GAIN"(project 8,01GM1910C),all by the Federal Ministry of Education and Research of Germanyby the FoFoLe program of the medical faculty of the LMU Munich.
文摘Immune dysregulation diseases are characterized by heterogeneous clinical manifestations and may have severe disease courses.The identification of the genetic causes of these diseases therefore has critical clinical implications.We performed whole-exome sequencing of patients with immune dysregulation disorders and identified two patients with previously undescribed mutations in LRRC32,which encodes glycoprotein A repetitions predominant(GARP).These patients were characterized by markedly reduced numbers and frequencies of regulatory T cells(Tregs).Tregs with mutated LRRC32 exhibited strongly diminished cell-surface GARP expression and reduced suppressor function.In a model of conditional Garp deficiency in mice,we confirmed increased susceptibility to inflammatory diseases once GARP expression on Tregs was decreased.Garp deficiency led to an unstable Treg phenotype due to diminished Foxp3 protein acetylation and stability.Our study reinforces the understanding of the immunological mechanisms of immune dysregulation and expands the knowledge on the immunological function of GARP as an important regulator of Treg stability.
基金funded by Research Fund of Zhejiang Provincial Health Commission (2025KY8662025)。
文摘Exertional heat stroke (EHS) is a life-threatening condition characterized by profound central nervous system (CNS)dysfunction and core temperature typically>40°C.^([1])This condition involves complex pathophysiological processes in which heat triggers a cascade of dysregulated inflammatory responses,endothelial dysfunction,coagulation abnormalities,and muscle damage.These processes can lead to multiorgan failure,significantly increasing the risk of mortality.^([2])Given the severity of EHS,early identification and timely intervention are crucial.However,there are no specific diagnostic markers for EHS,^([1])highlighting the need to identify reliable clinical parameters that can assist early decision-making.
基金supported by the National Key R&D Program of China(2023YFA1800100and 2024YFF1206600)the National Natural Science Foundation of China(32100664)the Basic and Applied Basic Research Foundation of Guangdong Province(2024B1515040019 and 2022A1515012042).
文摘Inflammatory bowel disease(IBD)comprises a heterogeneous group of chronic inflammatory conditions of the intestine.Current therapeutic strategies primarily focus on maintaining remission and mitigating the secondary effects rather than reversing its pathogenic mechanisms(Jeong et al.,2019).The pathogenesis of IBD involves intestinal barrier dysfunction,tissue damage,and dysregulated innate and adaptive immune responses(de Souza et al.,2017).Elevated neutrophil activity has been reported in IBD(Danne et al.,2024),yet the precise roles and mechanisms of neutrophils in disease progression remain to be elucidated.
基金supported by grants from Key laboratory of Ecology and Environment in Minority Area,National Ethnic Affairs Commission(KLEEMA202207)。
文摘The rapid expansion of urbanization has led to widespread exposure of wild birds to intensive light at night(LAN).While previous studies have established LAN-induced cognitive impairment in birds,the underlying neurobiological mechanisms remain poorly understood.We hypothesized that LAN exposure impaired cognitive function of birds potentially through neurodegeneration,metabolic dysregulation and neuroinflammatory responses in the telencephalon.Using Zebra Finches(Taeniopygia guttata)as an avian model,under 16L:8D photoperiods,we compared associative learning and memory abilities and neurobiological parameters between experimental groups exposed to dim light at night(LAN)versus nocturnal darkness(CTR).Compared to the CTR birds,the LAN-exposed birds exhibited significantly lower learning and memory performances,reduced neuron density and simplified dendritic morphology in the telencephalons.The key energy metabolic substrates(cholic acid,CTP,D-mannose-6-phosphate)and neuroprotective agents(trehalose,menaquinone,L-gulono-1,4-lactone)in the telencephalons of LAN-exposed birds showed depletion,while oxidative stress markers(methionine sulfoxide)and inflammatory mediators(cis-gondoic acid)exhibited elevation.The neurotransmitter dopamine and histamine metabolic pathway were disrupted in the LAN-exposed birds.The microglias were activated with pro-inflammatory IL-1βand IL-6 levels increasing and anti-inflammatory IL-10 decreasing in the telencephalons of the LAN-exposed birds.These findings indicate a potential mechanistic pathway whereby dim light exposure at night can induce neuroinflammation through oxidative stress-mediated microglial activation,energy metabolism and neurotransmitter homeostasis disruption,ultimately leading to neurodegeneration in the telencephalons of birds.
文摘BACKGROUND Synthetic messenger RNA(mRNA)vaccines have raised concerns regarding prolonged spike protein expression,immune activation,and potential off-target effects.AIM To investigate transcriptomic alterations in individuals with new-onset adverse events or cancer following mRNA coronavirus disease 2019 vaccination.METHODS Bulk RNA sequencing was performed on peripheral blood from two patient groups:(1)Individuals with new-onset nonmalignant adverse events;and(2)Individuals newly diagnosed with cancer post-vaccination.A control group of normal individuals was used for comparison.Differential gene expression was analyzed using DESeq2,and Gene Set Enrichment Analysis was conducted using the MSigDB database and custom gene sets.RESULTS Both vaccine patient groups displayed widespread transcriptional dysregulation.In the nonmalignant adverse event group,hallmark enrichments included mitochondrial dysfunction,proteasome-mediated stress,transcriptomic instability,and systemic inflammation.The cancer group exhibited additional hallmarks of genomic instability and epigenetic reprogramming.Nonsense-mediated decay,ribosomal stress,and myelocytomatosis oncogene activation were prominent in both groups,while immune signaling via toll-like receptors and type I interferons was particularly elevated in cancer patients.The observed transcriptomic profiles indicate cellular stress responses,mitochondrial dysfunction,and immune dysregulation following exposure to mRNA vaccines,potentially in susceptible individuals.CONCLUSION Shared and distinct molecular signatures in both cohorts demonstrate underlying mechanisms contributing to postvaccine symptomatology and complications,including oncogenesis and or progression of malignant disease.These findings underscore the need for a deeper investigation into the long-term safety of mRNA vaccines and host response variability.
文摘BACKGROUND Pituitary macroadenomas represent a significant challenge in clinical management due to their variable presentations and complex treatment considerations.This manuscript explores the multidisciplinary approach to understanding and managing pituitary macroadenomas,integrating neurosurgery,endocrinology,radiology,and pathology perspectives.AIM To summarize the literature on pituitary macroadenoma and outline the possible multidisciplinary approach in the diagnosis,management,and rehabilitation of individuals with pituitary adenomas,to add to already preexisting knowledge,in managing these cases enhancing better ocular and systemic outcomes.METHODS A search was conducted on an online publication database(PubMed)using the term“pituitary adenoma”including all results published over twenty years(2004-2024).Results were sorted for relevance,language,and completeness.RESULTS A total of 176 records were returned.The guidelines of the PRISMA 2020 statement were followed in this study.A total of 23 records were excluded due to being out of scope while a further 13 records were duplicates.Another 17 records were not available as full-length articles and were also excluded.The references of each included record was further searched for relevant publications.A total of 141 records were therefore used in this minireview.CONCLUSION Pituitary macroadenomas pose substantial clinical challenges due to their size and potential for significant hormonal and neurological impact,modern therapeutic strategies offer effective management options.Early detection and comprehensive treatment are essential for optimizing patient outcomes and maintaining quality of life.Continued research and advancements in medical technology are likely to further enhance the management and prognosis of this condition in the future.
文摘Cancer,a leading cause of global mortality,remains a significant challenge to increasing life expectancy worldwide.Forkhead Box R2(FOXR2),identified as an oncogene within the FOX gene family,plays a crucial role in developing various endoderm-derived organs.Recent studies have elucidated FOXR2-related pathways and their involvement in both tumor and non-tumor diseases.Dysregulation of FOXR2 has been linked to numerous malignant tumors,spanning the brain,nervous system,thyroid,osteosarcoma,Hodgkin lymphoma,colorectal,liver,pancreatic,lung,breast,ovarian,prostate,female genital tract,endometrial,and uterine cancers.Despite extensive research on FOXR2 dysregulation,its practical applications remain underexplored.This review delves into the mechanisms underlying FOXR2 dysregulation during oncogenesis and its implications for cancer diagnosis,prognosis,and treatment.
文摘Schizophrenia is a multifaceted neurodevelopmental disorder characterized by hallucinations,delusions,cognitive deficits,and emotional dysregulation.The prefrontal cortex(PFC),essential for executive functions,working memory,and emotional regulation,is notably impaired in this condition.This review consolidates current insights into the role of PFC dysfunction in schizophrenia,with a focus on its implications for therapeutic strategies.The neuroanatomical and neurobiological foundations of PFC dysfunction are explored,emphasizing structural abnormalities,functional dysconnectivity,and microcircuit disruptions that contribute to cognitive deficits and impaired decision-making.Clinical implications are discussed,particularly the correlation between PFC dysfunction and the severity and progression of schizophrenia symptoms.Additionally,pharmacological and non-pharmacological approaches aimed at modulating PFC activity are reviewed as potential therapeutic options.In conclusion,a deeper understanding of PFC dysfunction is pivotal for developing targeted treatments,and ongoing research offers promising avenues for enhancing outcomes for individuals affected by this debilitating disorder.
文摘Emerging evidence indicates that childhood stressors, such as familial conflict, bullying, academic pressure, and traumatic events, can significantly worsen inflammatory skin conditions like atopic dermatitis (AD) and psoriasis. This review explores the underlying neuroimmune pathways that link stress to skin inflammation in children, focusing on the role of the hypothalamic-pituitary-adrenal (HPA) axis and stress-induced cytokine production. Studies have shown that chronic psychological stress leads to dysregulation of the HPA axis, resulting in elevated cortisol levels, which paradoxically impair skin barrier function and upregulate pro-inflammatory cytokines such as IL-6, TNF-α, and IL-1β. Specific stressors, such as bullying, have been associated with heightened immune responses, increasing inflammation in the skin. For example, research has demonstrated that children who experience social stressors show elevated levels of C-reactive protein (CRP) and other markers of systemic inflammation, which directly correlate with skin condition flare-ups. Furthermore, exposure to early life stress has been linked to long-term alterations in immune function, perpetuating chronic inflammation even in the absence of ongoing stress. Future research should focus on longitudinal studies assessing how the timing, duration, and type of stressors influence skin condition severity, alongside evaluating interventions like cognitive-behavioral therapy (CBT) and stress management techniques. By addressing these childhood stressors, there is potential to not only mitigate skin condition flares but also reduce the long-term health consequences of chronic inflammation leading to therapeutic strategies that emphasize mental health alongside traditional dermatological treatments.
文摘Hepatitis C virus(HCV)infection has been increasingly associated with cardio-vascular complications,particularly atherosclerosis and cardiomyopathy,in addition to its primary hepatic effects.Studies indicate a higher prevalence of carotid atherosclerosis in patients with chronic hepatitis C infection,with viral load and steatosis emerging as independent risk factors.HCV-related athero-sclerosis appears to develop through complex processes involving endothelial dysfunction,inflammation,oxidative stress,and immune dysregulation.Key cytokines,including tumor necrosis factor-alpha and interleukin-6,increase inflammatory responses,while oxidative stress markers,such as malondial-dehyde,are associated with an increased risk of atherogenesis.In addition,HCV infection has been linked to cardiomyopathy.Direct viral effects,including HCV replication within cardiomyocytes and cytotoxicity induced by viral proteins,lead to myocardial injury and functional decline.Indirectly,HCV triggers immune-mediated damage,with heightened pro-inflammatory cytokines exacerbating cardiomyocyte apoptosis and fibrosis.Furthermore,HCV infection promotes a procoagulant imbalance,as evidenced by elevated factor VIII levels and thrombin potential,contributing to the increased cardiovascular risk.While substantial evidence indicates a relationship between HCV and cardiovascular disease,further research is needed to establish causality and guide therapeutic interventions.
文摘Functional gastrointestinal disorders,now termed“disorders of gut-brain interaction”(DGBI),are characterized by a spectrum of chronic gastrointestinal symptoms driven by dysregulated gut-brain interaction.DGBIs frequently coexist with liver diseases,including cirrhosis,thereby exacerbating clinical manifestations and complicating management;this overlap is underpinned by shared mechanisms,including gut dysbiosis,increased intestinal permeability,systemic inflammation,and altered neuroimmune signaling.Portal hypertension in cirrhosis promotes small intestinal bacterial overgrowth and microbial translocation,thereby triggering inflammatory pathways that worsen gut and liver function.This minireview explores the gut-liver axis as a central mediator in the interplay between DGBIs and liver disease/cirrhosis.Clinically,these interactions manifest as refractory gastrointestinal symptoms,nutritional deficiencies,and impaired quality of life.Emerging research emphasizes the need for integrative diagnostic approaches,such as combining advanced imaging,microbiome analysis,and biomarker profiling,to unravel the complex interplay between DGBIs and liver disease/cirrhosis.Therapeutic interventions targeting the gut microbiome,neuroimmune pathways,and lifestyle modification can mitigate disease burden.This review underscores the importance of a multidisciplinary framework for enhancing patient outcomes and guiding future research in this intersectional field.
基金Shenzhen Science and Technology Program(JCYJ20220818103013028)National Key Research and Development Program of China(2022YFC2702500 and 2022YFC2702503)。
文摘Objective:The etiology and pathogenesis of recurrent implantation failure(RIF)remain unclear.This study aimed to delineate the immune landscape and identify the pivotal biomarkers of immune dysregulation in RIF.Methods:Comprehensive bioinformatics analyses,including differential expression,functional enrichment,gene set enrichment,weighted gene co-expression network analysis,protein-protein interaction network,and machine learning analyses,were conducted to explore the immunological underpinnings of RIF.Results:Our findings demonstrated a significant downregulation in the expression of several immune-related gene sets in the RIF cohort,including those related to antigen processing and presentation,antimicrobial responses,chemokines and their receptors,cytokines,and natural killer cell cytotoxicity.These results provide evidence of a significant association between RIF and maternal-fetal immune dysregulation.Three signature genes(ANK3,PTGS2,andSLC39A2)were identified using various machine-learning methods.The diagnostic value and immunological relevance of these genes were confirmed in both discovery and validation cohorts.Conclusion:This study investigated the immune landscape of RIF using extensive bioinformatic analyses.Modular genes associated with both immune activity and RIF dysregulation were identified,providing new perspectives for understanding the pathophysiology and treatment of RIF.
文摘BACKGROUND Gestational diabetes mellitus(GDM)has recently been associated with abnormal profiles of inflammatory cells and cytokines,though the findings remain incon-sistent and unclear.AIM To elucidate the peripheral immune status in GDM.METHODS We systematically screened databases including Web of Science,PubMed,and EMBASE for eligible studies.Original articles reporting different immune cell levels in GDM compared to normal glucose-tolerance pregnant women were included to extract usable data.The pooled mean difference(MD)with 95%confidence interval(CI)was analyzed as the outcome measure.The Newcastle-Ottawa scale was employed to assess study quality.RESULTS A total of 19 studies involving various immune cell subgroups were included in our analysis.Specifically,total CD4+T cells(WMD=3.08;95%CI:0.81-5.35)were significantly increased in GDM groups.In contrast,total lymphocytes(SMD=0.05;95%CI:-0.16 to 0.26),CD3+T cells(SMD=-0.34;95%CI:-1.01 to 0.32),CD8+T cells(SMD=0.21;95%CI:-0.31 to 0.73),and natural killer T(NKT)Cells(SMD=0.83;95%CI:-1.10 to 2.75)showed no significant changes in GDM.Activation markers(HLA-DR+or CD69+)on CD4+T cells(WMD=0.20;95%CI:0.06-0.34)were increased in GDM patients.Treg cells,a classical subgroup of CD4+T cells,showed a decreasing trend in GDM compared to controls(SMD=-0.83;95%CI:-1.31 to-0.34).These results indicate an abnormal immune status in the peripheral profiles of GDM.CONCLUSION GDM may not only be a dysglycemia-related condition but also an immune disorder characterized by abnormal peripheral immune profiles,including higher levels of CD4+T cells and a reduced population of Treg cells.Tr-eating immune dysregulation could be a new direction for GDM management,although further research is needed to understand the precise mechanisms of immune overactivation in GDM.
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.
