Monomeric C-reactive protein:a link between chronic inflammation and neurodegeneration?

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.

Kdm6a-CNN1 axis orchestrates epigenetic control of traumainduced spinal cord microvascular endothelial cell senescence to balance neuroinflammation for improved neurological repair

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.

Ethyl acetate fraction of Sargassum pallidum extract attenuates particulate matter-induced oxidative stress and inflammation in keratinocytes and zebrafish

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.

Hepatoprotective effects of Xiaoyao San formula on hepatic steatosis and inflammation via regulating the sex hormones metabolism

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.

Inflammation as a cause of acute myocardial infarction in patients with myeloproliferative neoplasm

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.

Inflammation: Complexity and significance of cellular and molecular responses

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.

The miR-9-5p/CXCL11 pathway is a key target of hydrogen sulfide-mediated inhibition of neuroinflammation in hypoxic ischemic brain injury

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.

Efficacy of ginseng-based Renshenguben oral solution for cancer-related fatigue among patients with advanced-stage hepatocellular carcinoma:A prospective multicenter cohort study

Background:Cancer-related fatigue(CRF)is a common and debilitating symptom experienced by patients with advanced-stage cancer,especially those undergoing antitumor therapy.This study aimed to evaluate the efficacy and safety of Renshenguben(RSGB)oral solution,a ginseng-based traditional Chinese medicine,in alleviating CRF in patients with advanced hepatocellular carcinoma(HCC)receiving antitumor treatment.Methods:In this prospective,open-label,controlled,multicenter study,patients with advanced HCC at BCLC stage C and a brief fatigue inventory(BFI)score of≥4 were enrolled.Participants were assigned to the RSGB group(RSGB,10 mL twice daily)or the control group(with supportive care).Primary and secondary endpoints were the change in multidimensional fatigue inventory(MFI)score,and BFI and functional assessment of cancer therapy-hepatobiliary(FACT-Hep)scores at weeks 4 and 8 after enrollment.Adverse events(AEs)and toxicities were assessed.Results:A total of 409 participants were enrolled,with 206 assigned to the RSGB group.At week 4,there was a trend towards improvement,but the differences were not statistically significant.At week 8,the RSGB group exhibited a significantly lower MFI score(P<0.05)compared to the control group,indicating improved fatigue levels.Additionally,the RSGB group showed significantly greater decrease in BFI and FACT-Hep scores at week 8(P<0.05).Subgroup analyses among patients receiving various antitumor treatments showed similar results.Multivariate linear regression analyses revealed that the RSGB group experienced a significantly substantial decrease in MFI,BFI,and FACT-Hep scores at week 8.No serious drug-related AEs or toxicities were observed.Conclusions:RSGB oral solution effectively reduced CRF in patients with advanced HCC undergoing antitumor therapy over an eight-week period,with no discernible toxicities.These findings support the potential of RSGB oral solution as an adjunctive treatment for managing CRF in this patient population.

Novel insights in phosphodiesterase 4 subtype inhibition to target neuroinflammation and stimulate remyelination

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.

Neuroinflammation revisited through the microglial lens

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.

Advanced brain organoids for neuroinflammation disease modeling

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.

Neuroinflammation attenuation effects by celastrol and PDIA3 in the amygdala, hippocampus and dorsal raphe nucleus of obese mice

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.

Synthetic high-density lipoprotein(sHDL):a bioinspired nanotherapeutics for managing periapical bone inflammation

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.

Neuroinflammation as a therapeutic target in Huntington's disease

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.

Sex-dependent alterations in extracellular vesicles linking chronic spinal cord injury to brain neuroinflammation and neurodegeneration

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.

Human endogenous retrovirus type-W and multiple sclerosis–related smoldering neuroinflammation

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.

Identifying relevant factors influencing cancer-related fatigue in patients with diffuse large B-cell lymphoma during chemotherapy

BACKGROUND Diffuse large B-cell lymphoma(DLBCL)is a rapidly growing malignant tumor,and chemotherapy is one of the treatments used to combat it.Although advancements of science and technology have resulted in more and more patients being able to receive effective treatment,they still face side effects such as fatigue and weakness.It is important to thoroughly investigate the factors that contribute to cancer-related fatigue(CRF)during chemotherapy.AIM To explore the factors related to CRF,anxiety,depression,and mindfulness levels in patients with DLBCL during chemotherapy.METHODS General information was collected from the electronic medical records of eligible patients.Sleep quality and mindfulness level scores in patients with DLBCL during chemotherapy were evaluated by the Pittsburgh Sleep Quality Index and Five Facet Mindfulness Questionnaire-Short Form.The Piper Fatigue Scale was used to evaluate the CRF status.The Self-Rating Anxiety Scale and Self-Rating Depression Scale were used to evaluate anxiety and depression status.Univariate analysis and multivariate regression analysis were used to investigate the factors related to CRF.RESULTS The overall average CRF level in 62 patients with DLBCL during chemotherapy was 5.74±2.51.In 25 patients,the highest rate of mild fatigue was in the cognitive dimension(40.32%),and in 35 patients the highest moderate fatigue rate in the behavioral dimension(56.45%).In the emotional dimension,severe fatigue had the highest rate of occurrence,34 cases or 29.03%.The CRF score was positively correlated with cancer experience(all P<0.01)and negatively correlated with cancer treatment efficacy(all P<0.01).Tumor staging,chemotherapy cycle,self-efficacy level,and anxiety and depression level were related to CRF in patients with DLBCL during chemotherapy.CONCLUSION There was a significant correlation between CRF and perceptual control level in patients.Tumor staging,chemotherapy cycle,self-efficacy level,and anxiety and depression level influenced CRF in patients with DLBCL during chemotherapy.

Erratum to "Boeravinone B ameliorates allergic nasal inflammation by modulating the GATA-3/T-bet signaling pathway in a mouse model of allergic rhinitis"

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”.

Influence of aging,mitochondrial dysfunction,and inflammation on Parkinson's disease

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.

Systemic low-grade inflammation associated with specific depressive symptoms:insights from network analyses of five independent NHANES samples

To the editor:Major depressive disorder(MDD)is a heterogeneous disorder with varying symptom presentations and underlying biological mechanisms.1 The mainstream neurobiological hypotheses of depression involve monoamine neurotransmitters,hypothalamic-pituitary-adrenal axis,immune-inflammation and the glutamate system.