Microglial response to aging and neuroinflammation in the development of neurodegenerative diseases

Cellular senescence and chronic inflammation in response to aging are considered to be indicators of brain aging;they have a great impact on the aging process and are the main risk factors for neurodegeneration.Reviewing the microglial response to aging and neuroinflammation in neurodegenerative diseases will help understand the importance of microglia in neurodegenerative diseases.This review describes the origin and function of microglia and focuses on the role of different states of the microglial response to aging and chronic inflammation on the occurrence and development of neurodegenerative diseases,including Alzheimer's disease,Huntington's chorea,and Parkinson's disease.This review also describes the potential benefits of treating neurodegenerative diseases by modulating changes in microglial states.Therefore,inducing a shift from the neurotoxic to neuroprotective microglial state in neurodegenerative diseases induced by aging and chronic inflammation holds promise for the treatment of neurodegenerative diseases in the future.

Dual-directional regulation of spinal cord injury and the gut microbiota

There is increasing evidence that the gut microbiota affects the incidence and progression of central nervous system diseases via the brain-gut axis.The spinal cord is a vital important part of the central nervous system;however,the underlying association between spinal cord injury and gut interactions remains unknown.Recent studies suggest that patients with spinal cord injury frequently experience intestinal dysfunction and gut dysbiosis.Alterations in the gut microbiota can cause disruption in the intestinal barrier and trigger neurogenic inflammatory responses which may impede recovery after spinal cord injury.This review summarizes existing clinical and basic research on the relationship between the gut microbiota and spinal cord injury.Our research identified three key points.First,the gut microbiota in patients with spinal cord injury presents a key characteristic and gut dysbiosis may profoundly influence multiple organs and systems in patients with spinal cord injury.Second,following spinal cord injury,weakened intestinal peristalsis,prolonged intestinal transport time,and immune dysfunction of the intestine caused by abnormal autonomic nerve function,as well as frequent antibiotic treatment,may induce gut dysbiosis.Third,the gut microbiota and associated metabolites may act on central neurons and affect recovery after spinal cord injury;cytokines and the Toll-like receptor ligand pathways have been identified as crucial mechanisms in the communication between the gut microbiota and central nervous system.Fecal microbiota transplantation,probiotics,dietary interventions,and other therapies have been shown to serve a neuroprotective role in spinal cord injury by modulating the gut microbiota.Therapies targeting the gut microbiota or associated metabolites are a promising approach to promote functional recovery and improve the complications of spinal cord injury.

Major royal-jelly proteins intake modulates immune functions and gut microbiota in mice

In this study,we investigated the effects of major royal jelly proteins(MRJPs)on the estrogen,gut microbiota,and immunological responses in mice.Mice given 250 or 500 mg/kg,not 125 mg/kg of MRJPs,enhanced the proliferation of splenocytes in response to mitogens.The splenocytes and mesenteric lymphocytes activated by T-cell mitogens(Con A and anti-CD3/CD28 antibodies)released high levels of IL-2 but low levels of IFN-γand IL-17A.The release of IL-4 was unaffected by MRJPs.Additionally,splenocytes and mesenteric lymphocytes activated by LPS were prevented by MRJPs at the same dose as that required for producing IL-1βand IL-6,two pro-inflammatory cytokines.The production of IL-1β,IL-6,and IFN-γwas negatively associated with estrogen levels,which were higher in the MRJP-treated animals than in the control group.Analysis of the gut microbiota revealed that feeding mice 250 mg/kg of MRJPs maintained the stability of the natural intestinal microflora of mice.Additionally,the LEf Se analysis identified biomarkers in the MRJP-treated mice,including Prevotella,Bacillales,Enterobacteriales,Gammaproteobacteria,Candidatus_Arthromitus,and Shigella.Our results showed that MRJPs are important components of royal jelly that modulate host immunity and hormone levels and help maintain gut microbiota stability.

CRX-527 as a candidate adjuvant in a recombinant BCG-based malaria vaccine

Objective:To investigate the role of CRX-527,a Toll-like receptor 4 agonist,as the possible adjuvant for recombinant Mycobacterium bovis Bacillus Calmette-Guerin expressing merozoite surface protein 1C(BCG-MSP-1C).Methods:The mice were immunized with BCG and BCG-MSP-1C in the presence and absence of CRX-527.The untreated mice(injected with PBS-T80 only)were the negative control.The ability of CRX-527 to enhance IgG and its subclasses,as well as IL-4 and IFN-γproduction in the serum and spleen supernatant was evaluated using ELISA.Results:Mice immunized with BCG-MSP-1C exhibited the highest production of IgGs,IL-4 and IFN-γafter third immunization.In addition,CRX-527 further promoted the production of total IgG and IgG subclasses as well as IFN-γand IL-4 in the serum and splenocytes of immunized mice.Conclusions:CRX-527 has the potential as an adjuvant candidate for the candidate vaccines.Further study is needed to verify appropriate dosage for immunization and its efficacy.

Exercise training mode effects on myokine expression in healthy adults:A systematic review with meta-analysis

Background:The benefits of exercise are well known;however,many of the underlying molecular mechanisms are not fully understood.Skeletal muscle secretes myokines,which mediate muscleorgan crosstalk.Myokines regulate satellite-cell proliferation and migration,inflammatory cascade,insulin secretion,angiogenesis,fatty oxidation,and cancer suppression.To date,the effects of different exercise modes(namely,aerobic and resistance exercise)on myokine response remain to be elucidated.This is crucial considering the clinical implementation of exercise to enhance general health and wellbeing and as a medical treatment.Methods:A systematic search was undertaken in PubMed,MEDLINE,CINAHL,Embase,SPORTDiscus,andWeb of Science in April 2023.Eligible studies examining the effects of a single bout of exercise on interleukin15(IL-15),irisin,secreted protein acidic and rich in cysteine(SPARC),oncostatinM(OSM),and decorin were included.A random-effects meta-analysis was also undertaken to quantify the magnitude of change.Results:Sixty-two studies were included(n=1193).Overall,exercise appeared to induce small to large increases in myokine expression,with effects observed immediately after to 60 min post-exercise,although these were mostly not statistically significant.Both aerobic and resistance exercise resulted in changes in myokine levels,without any significant difference between training modes,and with the magnitude of change differing across myokines.Myokine levels returned to baseline levels within 180 min to 24 h post-exercise.However,owing to potential sources of heterogeneity,most changes were not statistically significant,indicating that precise conclusions cannot be drawn.Conclusion:Knowledge is limited but expanding with respect to the impact of overall and specific effects of exercise on myokine expression at different time points in the systemic circulation.Further research is required to investigate the effects of different exercise modes at multiple time points on myokine response.

Cytokine release syndrome triggered by programmed death 1 blockade(sintilimab)therapy in a psoriasis patient:A case report

BACKGROUND In recent years,immune checkpoint inhibitors(ICIs)have demonstrated remarkable efficacy across diverse malignancies.Notably,in patients with advanced gastric cancer,the use of programmed death 1(PD-1)blockade has significantly prolonged overall survival,marking a pivotal advancement comparable to the impact of Herceptin over the past two decades.While the therapeutic benefits of ICIs are evident,the increasing use of immunotherapy has led to an increase in immune-related adverse events.CASE SUMMARY This article presents the case of a patient with advanced gastric cancer and chronic plaque psoriasis.Following sintilimab therapy,the patient developed severe rashes accompanied by cytokine release syndrome(CRS).Fortunately,effective management was achieved through the administration of glucocorticoid,tocilizumab,and acitretin,which resulted in favorable outcomes.CONCLUSION Glucocorticoid and tocilizumab therapy was effective in managing CRS after PD-1 blockade therapy for gastric cancer in a patient with chronic plaque psoriasis.

The secondary injury cascade after spinal cord injury:an analysis of local cytokine/chemokine regulation

After spinal cord injury,there is an extensive infiltration of immune cells,which exacerbates the injury and leads to further neural degeneration.Therefore,a major aim of current research involves targeting the immune response as a treatment for spinal cord injury.Although much research has been performed analyzing the complex inflammatory process following spinal cord injury,there remain major discrepancies within previous literature regarding the timeline of local cytokine regulation.The objectives of this study were to establish an overview of the timeline of cytokine regulation for 2 weeks after spinal cord injury,identify sexual dimorphisms in terms of cytokine levels,and determine local cytokines that significantly change based on the severity of spinal cord injury.Rats were inflicted with either a mild contusion,moderate contusion,severe contusion,or complete transection,7 mm of spinal cord centered on the injury was harvested at varying times post-injury,and tissue homogenates were analyzed with a Cytokine/Chemokine 27-Plex assay.Results demonstrated pro-inflammatory cytokines including tumor necrosis factorα,interleukin-1β,and interleukin-6 were all upregulated after spinal cord injury,but returned to uninjured levels within approximately 24 hours post-injury,while chemokines including monocyte chemoattractant protein-1 remained upregulated for days post-injury.In contrast,several anti-inflammatory cytokines and growth factors including interleukin-10 and vascular endothelial growth factor were downregulated by 7 days post-injury.After spinal cord injury,tissue inhibitor of metalloproteinase-1,which specifically affects astrocytes involved in glial scar development,increased more than all other cytokines tested,reaching 26.9-fold higher than uninjured rats.After a mild injury,11 cytokines demonstrated sexual dimorphisms;however,after a severe contusion only leptin levels were different between female and male rats.In conclusion,pro-inflammatory cytokines initiate the inflammatory process and return to baseline within hours post-injury,chemokines continue to recruit immune cells for days post-injury,while anti-inflammatory cytokines are downregulated by a week post-injury,and sexual dimorphisms observed after mild injury subsided with more severe injuries.Results from this work define critical chemokines that influence immune cell infiltration and important cytokines involved in glial scar development after spinal cord injury,which are essential for researchers developing treatments targeting secondary damage after spinal cord injury.

Oligodendrocytes in central nervous system diseases:the effect of cytokine regulation

Cytokines including tumor necrosis factor, interleukins, interferons, and chemokines are abundantly produced in various diseases. As pleiotropic factors, cytokines are involved in nearly every aspect of cellular functions such as migration, survival, proliferation, and differentiation. Oligodendrocytes are the myelin-forming cells in the central nervous system and play critical roles in the conduction of action potentials, supply of metabolic components for axons, and other functions. Emerging evidence suggests that both oligodendrocytes and oligodendrocyte precursor cells are vulnerable to cytokines released under pathological conditions. This review mainly summarizes the effects of cytokines on oligodendrocyte lineage cells in central nervous system diseases. A comprehensive understanding of the effects of cytokines on oligodendrocyte lineage cells contributes to our understanding of central nervous system diseases and offers insights into treatment strategies.

Effect of aflibercept combined with triamcinolone acetonide on aqueous humor growth factor and inflammatory mediators in diabetic macular edema

AIM:To investigate the efficacy of aflibercept combined with sub-tenon injection of triamcinolone acetonide(TA)in treating diabetic macular edema(DME)and to examine changes in growth factors and inflammatory mediator levels in aqueous humor after injection.METHODS:Totally 67 DME patients(67 eyes)and 30 cataract patients(32 eyes)were enrolled as the DME group and the control group,respectively.The DME group was divided into the aflibercept group(34 cases)and the aflibercept combined with TA group(combined group,33 cases).The aqueous humor of both groups was collected during the study period.The aqueous levels of vascular endothelial growth factor(VEGF),monocyte chemoattractant protein-1(MCP-1),interleukin-6(IL-6),interleukin-8(IL-8),and interleukin-1β(IL-1β)were detected using a microsphere suspension array technology(Luminex 200TM).Aqueous cytokines,best-corrected visual acuity(BCVA),central macular thickness(CMT),and complications before and after treatment were compared between the aflibercept group and combined group.RESULTS:The concentrations of VEGF,MCP-1,IL-6,and IL-8 in the aqueous humor were significantly higher in the DME group than those of the control group(all P<0.01).After 1mo of surgery,the concentrations of VEGF,MCP-1,IL-6,and IL-8 in the aqueous humor were significantly lower in the combined group than those of the aflibercept group(all P<0.01).The BCVA and CMT values of the two groups were statistically different after 1 and 2mo of treatment(P<0.01).However,the difference was not statistically significant after 3mo of treatment(P>0.05).CONCLUSION:The cytokines VEGF,MCP-1,IL-6,and IL-8 in the aqueous humor of DME patients are significantly increased.Aflibercept and aflibercept combined with TA have good efficacy in DME patients,can effectively reduce CMT,improve the patient’s vision,and have high safety.Aflibercept combined with TA can quickly downregulate the aqueous humor cytokines and help to relieve macular edema rapidly.However,the long-term efficacy is comparable to that of aflibercept alone.

The dorsal root ganglion as a target for neurorestoration in neuropathic pain

Neuropathic pain is a severe and chronic condition widely found in the general population.The reason for this is the extensive variety of damage or diseases that can spark this unpleasant constant feeling in patients.During the processing of pain,the dorsal root ganglia constitute an important region where dorsal root ganglion neurons play a crucial role in the transmission and propagation of sensory electrical stimulation.Furthermore,the dorsal root ganglia have recently exhibited a regenerative capacity that should not be neglected in the understanding of the development and resolution of neuropathic pain and in the elucidation of innovative therapies.Here,we will review the complex interplay between cells(satellite glial cells and inflammatory cells)and factors(cytokines,neurotrophic factors and genetic factors)that takes place within the dorsal root ganglia and accounts for the generation of the aberrant excitation of primary sensory neurons occurring in neuropathic pain.More importantly,we will summarize an updated view of the current pharmacologic and nonpharmacologic therapies targeting the dorsal root ganglia for the treatment of neuropathic pain.

Nε-carboxymethyl-lysine and inflammatory cytokines,markers and mediators of coronary artery disease progression in diabetes

This editorial refers to the article“Comparative analysis of Nε-carboxymethyllysine and inflammatory markers in diabetic and non-diabetic coronary artery disease patients”,published in the recent issue of the World Journal of Diabetes 2023 is based on glucose metabolism,advanced glycation end products(AGEs),inflammation and adiposity on diabetes and coronary artery disease(CAD).This study has included CAD patients who were stratified according to glycosylated hemoglobin higher than 6.5 and sex-matched.A higher prevalence of hypertension,dyslipidemia,and non-vegetarian diet were found in the diabetic group.These risk factors might influence body weight and adiposity and explain the increment of the left atrium.Although this data was not supported by the study.The diet can also explain the non-enzymatic reactions on lipids,proteins,or nucleic acids and consequently an increment of AGEs.These molecules can emit fluorescence.However,one of the non-fluorescent and most abundant AGEs is Nε-carboxymethyl-lysine(CML).Its association with coronary artery stenosis and severity in the diabetic group might suggest its role as a player in CAD progression.Thus,CML,after binding with its receptor(RAGE),can induce calcification cascade through reactive oxygen species and mitogen-activated protein kinase.Moreover,this interaction AGE-RAGE can cause activation of the transcription nuclear factor-kb and induce inflammatory cytokines.It might explain the relationship between CML and pro-inflammatory cytokines in diabetic and CAD patients.Although this is a population from one center,the determination of CML and inflammatory cytokines might improve the diagnosis of severe and progressive CAD.Future and comparative studies among glycosylated hemoglobin,CML,and other AGE levels according to diagnosis and prognosis value might modify the clinical practice.Although these molecules are irreversible,they can act through a specific receptor inducing a signal transduction that might be modulated by inhibitors,antibodies,or siRNA.Further mechanistic studies might improve the development of future preventive therapies for diabetic patients.

Serum inflammatory markers in children with Mycoplasma pneumoniae pneumonia and their predictive value for mycoplasma severity

BACKGROUND Mycoplasma pneumoniae pneumonia(MPP)significantly impacts pediatric health,necessitating markers for early severe disease identification.AIM To investigate the correlation between serum inflammatory marker and the severity of MPP in children.METHODS A prospective study was carried out from January 2023 to November 2023.A total of 160 children with MPP who underwent treatment were selected:80 had severe MPP and 80 had mild MPP.Clinical and laboratory data were collected at the time of hospital admission and during hospitalization.Receiver operating characteristic curves were utilized to assess the diagnostic and prognostic for severe MPP.RESULTS Fever duration and length of hospitalization in pediatric patients with severe MPP exceeded those with mild MPP.The incidence of pleural effusion,lung consolidation,and bronchopneumonia on imaging was markedly elevated in the severe MPP cohort compared to the mild MPP cohort.In contrast to the mild cohort,there was a notable increase in C-reactive protein(CRP),procalcitonin(PCT),erythrocyte sedimentation rate,lactic dehydrogenase,D-dimer,and inflammatory cytokines[interleukin(IL)-6,IL-8,IL-10 and tumor necrosis factor(TNF)-α]in the severe MPP group were significantly higher.CONCLUSION Serum inflammatory markers(CRP,PCT,IL-6,D-dimer,IL-10 and TNF-α)were considered as predictors in children with severe MPP.

The anti-inflammatory effects of exercise on autoimmune diseases:A 20-year systematic review

Background:The anti-inflammatory effect of exercise may be an underlying factor in improving several autoimmune diseases.The aim of this systematic review was to examine the evidence on the role of exercise training in mitigating inflammation in adolescents and adults with autoimmune disease.Methods:PubMed,Web of Science,and Embase databases were systematically reviewed for related studies published between January 1,2003,and August 31,2023.All randomized and non-randomized controlled trials of exercise interventions with autoimmune disease study participants that evaluated inflammation-related biomarkers were included.The quality of evidence was assessed using the Tool for the assEssment of Study qualiTy and reporting in EXercise scale and Cochrane bias risk tool.Results:A total of 14,565 records were identified.After screening the titles,abstracts,and full texts,87 were eligible for the systematic review.These studies were conducted in 25 different countries and included a total of 2779 participants(patients with autoimmune disease,in exercise or control groups).Overall,the evidence suggests that inflammation-related markers such as C-reactive protein,interleukin 6,and tumor necrosis factor a were reduced by regular exercise interventions.Regular exercise interventions combined with multiple exercise modes were associated with greater benefits.Conclusion:Regular exercise training by patients with autoimmune disease exerts an anti-inflammatory influence.This systematic review provides support for the promotion and development of clinical exercise intervention programs for patients with autoimmune disease.Most patients with autoimmune disease can safely adopt moderate exercise training protocols,but changes in inflammation biomarkers will be modest at best.Acute exercise interventions are ineffective or even modestly but transiently pro-inflammatory.

Exercised blood plasma promotes hippocampal neurogenesis in the Alzheimer's disease rat brain

Background:Exercise training promotes brain plasticity and is associated with protection against cognitive impairment and Alzheimer’s disease(AD).These beneficial effects may be partly mediated by blood-borne factors.Here we used an in vitro model of AD to investigate effects of blood plasma from exercise-trained donors on neuronal viability,and an in vivo rat model of AD to test whether such plasma impacts cognitive function,amyloid pathology,and neurogenesis.Methods:Mouse hippocampal neuronal cells were exposed to AD-like stress using amyloid-βand treated with plasma collected from human male donors 3 h after a single bout of high-intensity exercise.For in vivo studies,blood was collected from exercise-trained young male Wistar rats(high-intensity intervals 5 days/week for 6 weeks).Transgenic AD rats(McGill-R-Thyl-APP)were inj ected 5 times/fortnight for 6 weeks at2 months or 5 months of age with either(a)plasma from the exercise-trained rats,(b)plasma from sedentary rats,or(c)saline.Cognitive function,amyloid plaque pathology,and neurogenesis were assessed.The plasma used for the treatment was analyzed for 23 cytokines.Results:Plasma from exercised donors enhanced cell viability by 44.1%(p=0.032)and reduced atrophy by 50.0%(p<0.001)in amyloid-β-treated cells.In vivo exercised plasma treatment did not alter cognitive function or amyloid plaque pathology but did increase hippocampal neurogenesis by~3 fold,regardless of pathological stage,when compared to saline-treated rats.Concentrations of 7 cytokines were significantly reduced in exercised plasma compared to sedentary plasma.Conclusion:Our proof-of-concept study demonstrates that plasma from exercise-trained donors can protect neuronal cells in culture and promote adult hippocampal neurogenesis in the AD rat brain.This effect may be partly due to reduced pro-inflammatory signaling molecules in exercised plasma.

Coumarin and eugenol ameliorate LPS-induced inflammation in RAW 264.7 cells via modulating the NLRP3 inflammasome pathway

Objective:To investigate the underlying mechanism of anti-inflammatory action of coumarin and eugenol in lipopolysaccharide(LPS)-stimulated RAW 264.7 cells.Methods:RAW 264.7 cells were treated with 2.5μg/mL of LPS,50μM of coumarin,and 50μM eugenol for 24 h.The viability of the cells was assessed using MTT assay.The production of nitric oxide was determined using Griess reagent and DCFH-DA was used to measure the production of reactive oxygen species.The protein expression of NLRP3,IL-1β,NF-κB,and cyclooxygenase 2 was assessed using Western blot analysis.Results:Coumarin and eugenol showed anti-inflammatory effects against LPS-induced inflammatory response by ameliorating the expression of NLRP3 inflammasome and NF-κB,which further led to a subsequent reduction in IL-1β,nitric oxide,and reactive oxygen species.Conclusions:Coumarin and eugenol exert their anti-inflammatory activities by modulating the NLRP3 inflammasome pathway and NF-κB.These compounds may have promising therapeutic applications for the treatment of various inflammatory diseases.

Potential role of tubulin glutamylation in neurodegenerative diseases

The differentiation of neuronal stem cells into mature neurons is a complex process that involves both structural and functional changes.As cells undergo differentiation,there are notable functional changes,including the expression of various transcription factors,cytokines,and neurotransmitiers.Additionally,structural changes occur as the cells develop various processes from the cell body and establish synaptic contacts with other cells.

Research progress on the correlation between aqueous humor components and pathogenesis and postoperative complications in patients with different types of cataracts

Aqueous humor provides the necessary nutrition for the lens and transports the metabolites in the eye.It was a liquid that can directly reflect the microenvironment in the eye'and it can be easily obtained during the operation.This review intended to analyze the components of aqueous humor in patients with different types of cataracts'so as to reflect the pathogenesis and development of the disease'evaluate the incidence of postoperative complications and provide reference value for the surgical design of sequential cataract surgery.The aqueous humor components of different types of cataracts showed different degrees of inflammation'oxidative stress and extracellular matrix remodeling.The biomarker of early neuropathy in diabetic cataract was neural cell adhesion molecule-1(NCAM1).Transforming growth factor-β(TGF-β)was the evaluation factor of disease development in patients with pseudoexfoliation syndrome.The relationships between postoperative complications of different types of cataracts and aqueous humor components were as follows:Macular edema after diabetic cataract surgery was associated with tumor necrosis factor-alpha;capsular contraction after high myopic cataract surgery was related to monocyte chemoattractant protein-1(MCP-1)and TGF-β2;Klotho and glutathione S-transferase P 1(GSTP1)were associated with high intraocular pressure after primary open-angle glaucoma complicated by cataract surgery;capsular contraction after retinitis pigmentosa complicated by cataract surgery was associated with matrix metalloproteinases;pro-inflammatory cytokines and fibroblast growth factor 4 in the aqueous humor of congenital cataracts were associated with posterior capsular opacification after surgery.Granulocyte colony stimulating factor 3 and MCP-1 were the main cytokines mediating the pain of the second eye in the binocular sequential cataract surgery short interval(1 wk)'while MCP-1 mediated pain in the long interval(6 wk).The second eye after binocular sequential cataract surgery had a higher level of proinflammatory factors.The components of aqueous humor in patients with different types of cataracts were related to the pathogenesis and postoperative complications of the disease.Monitoring the components of the aqueous humor could help better understand the intraocular microenvironment of different types of cataracts and provide a reference for predicting the development of the disease and implementing relevant targeted therapy.

Association of Cytokines with Clinical Indicators in Patients with Drug-Induced Liver Injury

Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators.Method The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with DILI.Based on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),antiinfective drugs,and other drugs,patients were divided into five groups.Cytokines were measured by Luminex technology.Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed.Results 73 patients were enrolled.Age among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine group.Interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs group.There was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs group.Conclusion Older age may be more prone to DILI.Patients with NSAIDs have more severe liver damage in early stages of DILI,TNF-αand IL-6 may partake the inflammatory process of DILI.

Peripheral mitochondrial DNA as a neuroinflammatory biomarker for major depressive disorder

In the pathogenesis of major depressive disorder, chronic stress-related neuroinflammation hinders favorable prognosis and antidepressant response. Mitochondrial DNA may be an inflammatory trigger, after its release from stress-induced dysfunctional central nervous system mitochondria into peripheral circulation. This evidence supports the potential use of peripheral mitochondrial DNA as a neuroinflammatory biomarker for the diagnosis and treatment of major depressive disorder. Herein, we critically review the neuroinflammation theory in major depressive disorder, providing compelling evidence that mitochondrial DNA release acts as a critical biological substrate, and that it constitutes the neuroinflammatory disease pathway. After its release, mitochondrial DNA can be carried in the exosomes and transported to extracellular spaces in the central nervous system and peripheral circulation. Detectable exosomes render encaged mitochondrial DNA relatively stable. This mitochondrial DNA in peripheral circulation can thus be directly detected in clinical practice. These characteristics illustrate the potential for mitochondrial DNA to serve as an innovative clinical biomarker and molecular treatment target for major depressive disorder. This review also highlights the future potential value of clinical applications combining mitochondrial DNA with a panel of other biomarkers, to improve diagnostic precision in major depressive disorder.

Effects of different doses of glucose and fructose on central metabolic pathways and intercellular wireless communication networks in humans

Fructose and glucose are often widely used in food processing and may contribute to many metabolic diseases.To observe the effects of different doses of glucose and fructose on human metabolism and cellular communication,volunteers were given low,medium,and high doses of glucose and fructose.Serum cytokines,glucose,lactate,nicotinamide adenine dinucleotide(NADH)and metabolic enzymes were assayed,and central carbon metabolic pathway networks and cytokine communication networks were constructed.The results showed that the glucose and fructose groups basically maintained the trend of decreasing catabolism and increasing anabolism with increasing dose.Compared with glucose,low-dose fructose decreased catabolism and increased anabolism,significantly enhanced the expression of the inflammatory cytokine interferon-γ(IFN-γ),macrophage-derived chemokine(MDC),induced protein-10(IP-10),and eotaxin,and significantly reduced the activity of isocitrate dehydrogenase(ICDH)and pyruvate dehydrogenase complexes(PDHC).Both medium and high doses of fructose increase catabolism and anabolism,and there are more cytokines and enzymes with significant changes.Furthermore,multiple cytokines and enzymes show strong relevance to metabolic regulation by altering the transcription and expression of enzymes in central carbon metabolic pathways.Therefore,excessive intake of fructose should be reduced to avoid excessive inflammatory responses,allergic reactions and autoimmune diseases.