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.

FUCOIDIN INHIBITS OXIDIZED LOW DENSITY LIPOPROTEIN FROM INDUCING HUMAN PERIPHERAL BLOOD MONOCYTE EXPRESSION OF PROINFLAMMATORY CYTOKINES mRNA

Objective To study the significance of scavenger receptor class A(SR A)in mediating human peripheral blood monocyte to uptake oxidized low density lipoprotein(OxLDL) and promoting the atherosclerotic immuno pathological lesion in the local blood vessel. Methods With the Digoxenin labeled Oligonucleotide probes In situ Hybridization, this research investigated the effects of OxLDL on the mRNA expression of proinflammatory cytokines including MCP 1, bFGF, PDGF and IL 10 in the human peripheral blood monocyte and whether fucoidin, a peculiarly inhibitory ligand for SR A, would influence this process. Results Monocyte was significantly increased the mRNA expression of MCP 1, bFGF, PDGF and IL 10 in a dose dependent manner after incubating with OxLDL (10,15,20,25,30?mg·L -1 , respectively)for 24 hours( P < 0.001 ). Fucoidin(50,100,150,200,250?mg·mL -1 , respectively)completely inhibited OxLDL(20?mg·L -1 )from inducing monocyte the mRNA expression of above proinflammatory cytokines( P < 0.001 ). Conclusion OxLDL can stimulate human peripheral blood monocyte to give expression to proinflammatory cytokines mRNA in a dose dependent manner, while a peculiarly inhibitory ligand for SR A fucoidin has an obviously opposed role.

Proliferation and Apoptosis of Bone Marrow CD4^+ T Cells in Patients with Aplastic Anemia and Impacts of the Secreted Cytokines on Hematopoietic Stem Cells from Umbilical Cord Blood

Recent studies indicate that immune-associated aplastic anemia(AA)resembles such autoimmune diseases as insulin-dependent diabetes and chronic autoimmune thyroiditis that belong to organ-specific autoimmune diseases.Many independent investigation groups have successfully isolated the pathopoiesis-associated T cell clone causing hematopoiesis failure with a CD4 phenotype from peripheral blood and bone marrow(BM)in AA patients.In the current study,BM CD4+ T cells were isolated from AA patients and healthy con...

Predictive effect of lipopolysaccharide-stimulated inflammatory cytokines on symptoms of generalized anxiety disorder

BACKGROUND Generalized anxiety disorder(GAD)is a relatively common mental disorder.Recently,inflammation,an important factor for the development of depression,has attracted increasing attention.Several studies have shown that inflammatory cytokines can affect the pathophysiological processes of several nervous system diseases.We hypothesized that there is a correlation between the levels of lipopolysaccharide(LPS)-stimulated inflammatory cytokines and the clinical symptoms of GAD.AIM To investigate the predictive effect of LPS-stimulated inflammatory cytokines on symptoms of GAD.METHODS This was a cross-sectional study in which 89 patients with GAD diagnosed at The First Hospital of Hebei Medical University from January 2022 to December 2022 and 70 individuals without anxiety and depression(controls)during the same period were included.Fasting venous blood was collected from all the subjects in heparin tubes,and another 3 ml of blood was supplemented with LPS(10 ng/ml).The plasma levels of 12 cytokines[Interleukin(IL)-1β,IL-2,IL-4,IL-5,IL-6,IL-8,IL-10,tumor necrosis factor(TNF)-α,interferon(IFN)-γ,IL-17A,IL-12p70,and IFN-α]were detected.RESULTS Post-LPS stimulation,the levels of IL-1β,IL-6,IL-8,IL-10,and TNF-αin both the control and GAD groups were significantly elevated above those in the nonstimulated groups,with IL-6 and IL-8 showing marked increases.Increases in IL-8 and TNF-αwere statistically significant in the GAD group(P<0.05).IL-1β,IL-6,IL-8,IL-10,and TNF-αwere found to be significantly correlated with Hamilton Anxiety Rating Scale(HAMA)scores(P<0.05).A negative correlation was observed between IL-10 levels and HAMA scores.Further analysis revealed that TNF-αwas associated with mental anxiety,whereas IL-1β,IL-8,and IL-10 were associated with physical anxiety symptoms,with IL-10 showing a negative correlation with physical anxiety.IL-6 was associated with both mental and physical aspects of anxiety.CONCLUSION The physical symptoms of GAD are related to inflammatory factors.IL-1β,IL-8,IL-10,and TNF-a can be used as predictors of physical or mental anxiety in patients with GAD.

Lentivirus Transduced T Cell Lines Response to Pro-Inflammatory and Antiviral Cytokines in the Presence of HIV

Various studies have attempted to understand HIV infection under a diverse range of stimulants including cytokine stimulation. Pro-inflammatory cytokines, such as TNF-α, have been shown to reactivate HIV latency by inducing NF-κB mediated activation of the HIV LTR (long terminal repeats) that contain κB transcriptional binding sites. Interferon-alpha (IFN-α), an anti-viral cytokine, is not well studied as an inducer of HIV activation. However, previous work from our group has shown that HIV can block IFN-α signaling in CD4+ T cells presumably to allow for further viral replication. Initially using HEK 293T cells, we moved to CD4+ T cells lines to develop a system to determine how stimulation with different cytokines impacts signaling within T cell lines. We confirmed that in our system TNF-α triggers activation of NF-κB driven reporters but not in the presence of HIV. In addition, we show that the presence of HIV blocks IFN-α signaling. Taken together, our system demonstrates that HIV by TNF-α, will continue to block IFN-α signaling preventing it from impacting HIV activation. This system can now be used to screen for cytokine based and other molecule activators that may be influenced by the presence of HIV.

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.

Interaction between serum inflammatory cytokines and brain-derived neurotrophic factor in cognitive function among first-episode schizophrenia patients

BACKGROUND The pathogenesis of cognitive impairment in schizophrenia(SCZ)remains unclear.Accumulating studies showed that inflammatory-immune dysregulation and altered brain derived neurotrophic factor(BDNF)levels play a crucial role in the psychopathology of SCZ.However,their association with cognitive dysfunction in first-episode SCZ patients has not been thoroughly investigated.AIM To explore the interaction effects between cognitive function and inflammatory cytokines and BDNF in first-episode SCZ.METHODS The current study is a cross-sectional case-control investigation that recruited 84 patients with first-episode SCZ(SCZ group)and 80 healthy controls(HCs group)at the Huzhou Third Municipal Hospital between August 2021 and September 2023.ELISA was employed to measure the serum levels of interleukin(IL)-1β,IL-4,IL-6,IL-10,and BDNF.The Chinese brief cognitive test(C-BCT)and the positive and negative syndrome scales were measured the severity of cognitive impairment and psychiatric symptoms.RESULTS Compared to the HC group,the SCZ group exhibited elevated IL-1βand IL-6 levels,decreased BDNF levels,and reduced C-BCT scores(all P<0.001).In SCZ,BDNF was negatively correlated with IL-6(r=-0.324,P<0.05).Information processing speed was negatively correlated with IL-6(r=-0.315,P<0.05)and positively with BDNF(r=0.290,P<0.05);attention,working memory,comprehensive ability,and executive function were negatively correlated with IL-1βand IL-6(all P<0.05)and positively with BDNF(all P<0.05).Multiple regression analysis showed IL-6 influenced C-BCT dimensions(β=-0.218 to-0.327,all P<0.05);attention and executive ability were influenced by IL-1β(β=-0.199 to-0.261,all P<0.05);comprehensive executive ability was influenced by BDNF(β=0.209,P<0.05).CONCLUSION Our findings suggested that interrelationships between immune dysfunction and neurotrophic deficiency might underlie the pathological mechanisms of cognitive impairments in first-episode SCZ patients.

Differential expression of plasma cytokines in sepsis patients and their clinical implications

BACKGROUND Sepsis,which is characterized by acute systemic inflammation and is associated with high rates of morbidity and mortality,presents a significant challenge in health care.Some scholars have found that the sequential organ failure assessment(SOFA)and quick SOFA scores are not ideal for predicting severe sepsis and mortality.Microbial culture takes a long time(2-3 d)and provides no information for early diagnosis and treatment.Therefore,new diagnostic methods for sepsis need to be explored.AIM To assess cytokine levels in the plasma of sepsis patients and identify potential biomarkers for diagnosing sepsis.METHODS Ten sepsis patients admitted to the emergency department within 24 h of onset were enrolled as the observation group,whereas ten noninfected patients served as the control group.Of the 10 noninfected patients,9 hypertension combined with cerebral infarction,1 patients with vertiginous syndrome.Plasma Cytokines were measured using the Bio-Plex Pro^(TM)Human Chemokine Panel 40-plex.Differentially expressed cytokines in plasma of sepsis and nonsepsis patients were analyzed using Gene Ontology(GO)functional enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses.RESULTS Interleukin(IL)-16,granulocyte-macrophage granulocyte-macrophage colony-stimulating factor(GM-CSF),CX3CL1,CXCL9,CXCL16,CCL25,and CCL23 plasma levels were significantly increased in sepsis patients.GO analysis revealed that these cytokines were mainly associated with cellular structures such as intermediates,nuclear plaques,adhesion plaques,lateral plasma membranes,and cell matrix junctions.These genes were involved in various molecular functions,such as cytokine activity,receptor ligand activity,and signal receptor activator activity,contributing to various biological functions,such as leukocyte chemotaxis,migration,and chemotaxis.KEGG analysis indicated involvement in cytokine cytokine receptor interactions,chemokine signaling pathways,virus–protein interactions with cytokines and cytokine receptors,and the tumor necrosis factor signaling pathway.CONCLUSION Elevated serum levels of IL-16,GM-CSF,CX3CL1,CXCL9,CXCL16,CCL25,and CCL23 in sepsis patients suggest their potential as diagnostic biomarkers for sepsis.

DNA Damage-driven Inflammatory Cytokines:Reprogramming of Tumor Immune Microenvironment and Application of Oncotherapy

DNA damage occurs across tumorigenesis and tumor development.Tumor intrinsic DNA damage can not only increase the risk of mutations responsible for tumor generation but also initiate a cellular stress response to orchestrate the tumor immune microenvironment(TIME)and dominate tumor progression.Accumulating evidence documents that multiple signaling pathways,including cyclic GMP-AMP synthase-stimulator of interferon genes(cGAS-STING)and ataxia telangiectasia-mutated protein/ataxia telangiectasia and Rad3-related protein(ATM/ATR),are activated downstream of DNA damage and they are associated with the secretion of diverse cytokines.These cytokines possess multifaced functions in the anti-tumor immune response.Thus,it is necessary to deeply interpret the complex TIME reshaped by damaged DNA and tumor-derived cytokines,critical for the development of effective tumor therapies.This manuscript comprehensively reviews the relationship between the DNA damage response and related cytokines in tumors and depicts the dual immunoregulatory roles of these cytokines.We also summarize clinical trials targeting signaling pathways and cytokines associated with DNA damage and provide future perspectives on emerging technologies.

Indications of pro-inflammatory cytokines in laparoscopic and open liver resection for early-stage hepatocellular carcinoma

Background:Our clinical practice of laparoscopic liver resection(LLR)had achieved better short-term and long-term benefits for patients with hepatocellular carcinoma(HCC)over open liver resection(OLR),but the underlying mechanisms are not clear.This study was to find out whether systemic inflammation plays an important role.Methods:A total of 103 patients with early-stage HCC under liver resection were enrolled(LLR group,n=53;OLR group,n=50).The expression of 9 inflammatory cytokines in patients at preoperation,postoperative day 1(POD1)and POD7 was quantified by Luminex Multiplex assay.The relationships of the cytokines and the postoperative outcomes were compared between LLR and OLR.Results:Seven of the circulating cytokines were found to be significantly upregulated on POD1 after LLR or OLR compared to their preoperative levels.Compared to OLR,the POD1 levels of granulocytemacrophage colony-stimulating factor(GM-CSF),interleukin-6(IL-6),IL-8,and monocyte chemoattractant protein-1(MCP-1)in the LLR group were significantly lower.Higher POD1 levels of these cytokines were significantly correlated with longer operative time and higher volume of blood loss during operation.The levels of these cytokines were positively associated with postoperative liver injury,and the length of hospital stay.Importantly,a high level of IL-6 at POD1 was a risk factor for HCC recurrence and poor disease-free survival after liver resection.Conclusions:Significantly lower level of GM-CSF,IL-6,IL-8,and MCP-1 after liver resection represented a milder systemic inflammation which might be an important mechanism to offer better short-term and long-term outcomes in LLR over OLR.

Content of blood cell components,inflammatory cytokines and growth factors in autologous platelet-rich plasma obtained by various methods

BACKGROUND The evaluation of the efficacy of platelet-rich plasma(PRP) in clinical practice yields conflicting results and raises numerous controversies. This may be due to different concentrations of biologically active components in PRP obtained with the use of different methods of gravity separation.AIM To compare the content, repeatability and correlations between biologically active components in PRP obtained with four different commercial systems.METHODS From a whole blood sample of each of 12 healthy male volunteers, 4 PRP samples were prepared using 4 different commercial kits [Arthrex Autologous Conditioned Plasma(ACP), Mini GPS Ⅲ, Xerthra, Dr. PRP] in accordance with the instructions provided by the manufacturers. A comparative analysis of blood cell components-13 selected inflammatory cytokines and 7 growth factors-in the obtained PRP samples was performed using the Kruskal-Wallis test by ranks. The repeatability of results in each method was evaluated by the estimation of the coefficient of variation. The Spearman correlation was used to estimate the relationship between blood cell content and cytokines.RESULTS Significantly higher concentrations of platelets(PLT), white blood cells(WBC) and red blood cells(RBC) were found in PRP obtained with the use of Mini GPS Ⅲ than in PRP obtained using other systems. Significant differences in the content of growth factors and cytokines in PRP were found. A positive correlation of the amount of PLT, RBC and WBC with the concentration of most of the growth factors was found but in only three inflammatory cytokines. The obtained correlations between blood cell components and cytokines differed between the systems in terms of statistical significance, which may be due to insufficient sample size. The repeatability of the obtained PLT concentration also varied between protocols with the lowest in Xerthra and the highest in Arthrex ACP.CONCLUSION Significant differences in the content of biologically active components and their repeatability were found in PRP obtained by various methods, providing new data for further research.

Lactobacilli,bifi dobacteria and E.coli nissle induce pro-and anti-inflammatory cytokines in peripheral blood mononuclear cells

AIM： To investigate whether the stimulation of peripheral blood mononuclear cells （PBMNC） with the cell debris and cell extraction of different probiotic strains is similar or species specific. METHODS： Three strains of bifidobacteria, 4 strains of lactobacilli, and E. coli nissle were sonicated and centrifuged in order to divide them into cell extract and cell debris. PBMNC were separated by density gradient and incubated for 36 h with either the cell debris or the cell extract of single strains of probiotic bacteria in doses from 10^2 to 10^8 CFU/mL. Cell supernatants were taken and interleukin （IL）-10, IL-1β, and tumor necosis factor （TNF）-α were determined by ELISA. RESULTS： Depending on the species super-family, the strains had different stimulation patterns. Except for both L. casei strains, the cell extract of bitTdobacteria and/actobacilli had less stimulating capacity than cell debris, whereas the cell extract of E. coli nissle had similar stimulating properties to that of the cell debris of the strain and significantly more stimulating capacity than that of bifidobacteria and lactobacilli. The cell debris of bifidobacteria stimulated more cytokine release than the cell debris of lactobacilli. The cell debris of lactobacilli did not have a stimulating capacity when lower concentrations were used. Neither cell extraction nor cell debris had an inhibitory effect on the production of the tested cytokines by stimulated PBMNC. CONCLUSION： The incubation of probiotic strains, which have been used in clinical trials for inflammatory diseases, with immunocompetent cells leads to different species specific reactions. High IL-10 response to cell debris of bifidobacteria and E. coli nissle can be found. This corresponds to positive effects of bihdobacteria and E. coli nissle in clinical trials for inflammatory bowel disease compared to negative outcomes obtained with lactobacilli.

Lethal effect of mononuclear cells derived from human umbilical cord blood differentiating into dendritic cells after in vitro induction of cytokines on neuroblastoma cells

BACKGROUND： Dendritic cell is the most major antigen presenting cell of organism. It is proved in recent studies that human umbilical cord blood mononuclear cells induced and cultured in vitro by recombinant human granulocyte-macrophage colony stimulating factor （rhG-MCSF） and recombinant human interleukin-4 （rhlL-4） can generate a great many dendritic cells and promote the lethal effect of T cells on human neuroblastoma, but it is unclear that whether the lethal effect is associated with the most proper concentration of dendritic cells. OBJEETIVE： To investigate the lethal effect of human umbilical cord blood mononuclear cells induced in vitro by cytokines differentiating into dendritic cells on human neuroblastoma, and its best concentration range. DESIGN ： Open experiment SEI-FING： Department of Pediatrics, the Medical School Hospital of Qingdao University MATERIALS ： The study was carried out in the Shandong Provincial Key Laboratory （Laboratory for the Department of Pediatrics of the Medical School Hospital of Qingdao University） during September 2005 to May 2006. Human umbilical cord blood samples were taken from the healthy newborn infants of full-term normal delivery during October to November 2005 in the Medical School Hospital of Qingdao University, and were voluntarily donated by the puerperas. Main instruments： type 3111 CO2 incubator （Forma Scientific, USA）, type 550 ELISA Reader （Bio-Rad, USA）. Main reagents： neuroblastoma cell line SK-N-SH （Shanghai Institute of Life Science, Chinese Academy of Sciences）, RPMI-1640 culture fluid and fetal bovine serum （Hyclone）, rhlL-4 （Promega, USA）, rhG-MCSF （Harbin Pharmaceutic Group Bioengineering Co.Ltd）, rat anti-human CDla monoclonal antibody and FITC-labeled rabbit anti-rat IgG （Xiehe Stem cell Gene Engineering Co.Ltd）. METHODS： ① Human umbilical cord blood mononuclear cells obtained with attachment methods differentiated into human umbilical cord blood dendritic cells, presenting typical morphology of dendritic cells after in vitro induction by rhG-MCSF and rhlL-4. ② Different concentrations of dendritic cells[ dendritic cells： neuroblastoma cells=20：1,50：1,100：1 （2×10^8 L^-1,5×10^8 L^-1,1×10^9 L^-1）], 1×10^9 L^-1 T cells and 1×10^7 L^-1 neuroblastoma cells were added in the experimental group. 1 ×10^9 L^-1 T cells and 1 ×10^7 L^-1 neuroblastoma cells were added in the control group. ③ Main surface marker CDla molecules of dendritic cells were detected with indirect immunofluorescence, and the percent rate of dendritic cells was counted with ultraviolet light and expressed as the expression rate of CD1a^＋ cells. ④Single effector cells and target cells were respectively set in the experimental group and control group to obtain the lethal effect. The lethal effect of dendritic cells on neuroblastoma cells was indirectly evaluated by detecting cellular survival with MTT assay. The lethal effect（%）= （1-A experimentat well-A effector cell /A target cell well）×100%.⑤The expenmental data were presented as Mean ±SD, and paired t test was used. MAIN OUTCOME MEASURES： ① Morphological characters of dendritic cells in the process of induction and differentiation. ②CD1a^＋ cellular expression rate. ③Lethal effect of dendntic cells on neuroblastoma cells. RESULTS： ①Morphological characters of dendritic cells in the process of induction and differentiation： On the 15^th day after human umbilical cord blood mononuclear cells were induced by rhG-MCSF and rhlL-4, typical morphology of dendritic cells could be seen under an inverted microscope. ②Expression rate of CD1a^＋ cells was （43.12±5.83）%. ③Lethal effect of dendritic cells on neuroblastoma cells： Lethal effect of dendritic cells stimulated T cells in each experimental group （ dendritic cells： neuroblastoma cells=100：1,50：1, 20：1 respectively） on neuroblastoma cells was significantly higher than that in control group[（31.00 ±4.41 ）%, （30.92±5.27）%,（33.57±5.35）%,（26.23±5.20）%, t=3.51,2.98,4.24, P〈 0.01 ）; But the lethal effect of dendntic cells on neuroblastoma was significantly lower when their ratio was 100：1 and 50：1 in comparison with 20：1 （t=2.01,2.36, P 〈 0.05）, and no significant difference in lethal effect existed between the ratio at 100：1 and 50：1 （t=0.06,P 〉 0.05）. CONCLUSION： Dendritic cells differentiated from human umbilical cord blood mononuclear cells after in vitro induction of cytokines can promote the lethal effect of T cells on neuroblastoma cells. The lethal effect is associated with the concentration of dendritic cells within some range.

Effects of Lycium barbarum polysaccharide on cytokines in adolescents with subthreshold depression:a randomized controlled study

Strong evidence has accumulated to show a correlation between depression symptoms and inflammatory responses.Moreover,anti-inflammatory treatment has shown partial effectiveness in alleviating depression symptoms.Lycium barbarum polysaccharide(LBP),derived from Goji berries,exhibits notable antioxidative and anti-inflammatory properties.In our recent double-blinded randomized placebo-controlled trial,we found that LBP significantly reduced depressive symptoms in adolescents with subthreshold depression.It is presumed that the antidepressant effect of LBP may be associated with its influence on inflammatory cytokines.In the double-blinded randomized controlled trial,we enrolled 29 adolescents with subthreshold depression and randomly divided them into an LBP group and a placebo group.In the LBP group,adolescents were given 300 mg/d LBP.A 6-week follow up was completed by 24 adolescents,comprising 14 adolescents from the LBP group(15.36±2.06 years,3 men and 11 women)and 10 adolescents from the placebo group(14.9±1.6 years,2 men and 8 women).Our results showed that after 6 weeks of treatment,the interleukin-17A level in the LBP group was lower than that in the placebo group.Network analysis showed that LBP reduced the correlations and connectivity between inflammatory factors,which were associated with the improvement in depressive symptoms.These findings suggest that 6-week administration of LBP suppresses the immune response by reducing interleukin-17A level,thereby exerting an antidepressant effect.

Expression and Clinical Significance of Various Cytokines in Otitis Media

The expression and clinical significance of relevant cytokines in otitis media (OM) are discussed, and the alterations to the pathological state of the otitis media mucosa are further understood through the study of cytokine transduction pathways. More and more studies have shown that relevant cell proliferation and inflammation progression pathways play a role in the development of otitis media, such as the Jun amino-terminal protein kinase (JNK) mitogen-activated protein kinase (MAPK) signaling pathway, the NF-κB signaling pathway, and the PI3K/AKT/PTEN pathway, which are involved in the proliferation of the middle ear mucosa during otitis media, which affects the mucosal cilia, motor function, Eustachian tube function, and the mucosal ciliary function. These studies provide new ideas for the treatment of otitis media and further explore the feasibility of immunotherapy in the future treatment of otitis media. In this paper, we present a review of the latest research progress on the expression of various cytokines in otitis media.

Cytokines Released from Allergen-Stimulated Blood Cells during the Delayed Asthmatic Response to Allergen Challenge

Background: Bronchial asthma patients may develop various asthmatic response types to bronchial challenge with allergen, such as immediate (IAR), late (LAR), dual (DAR) or delayed (DYAR), due to different immunologic mechanisms. The DYAR, beginning between 26-32 hrs and lasting up to 56 hrs after the allergen challenge, differs from the IAR, LAR and DAR in clinical, diagnostic and immunologic aspects. The aim of this study was to investigate the concentrations of the particular intracellular cytokines released by blood cells stimulated with relevant allergens “in vitro”, before and during the DYAR. Methods: In 23 patients, the repeated DYAR (p < 0.001) was supplemented with cytokine determination in the supernatants of the blood cells stimulated with relevant allergens before and up to 72 hours after the bronchial challenge, by means of enzyme-linked immunoassay. Results: The significantly elevated pre-challenge concentrations (p < 0.05) of IL-2, IL-17, IFN-γ and G-CSF released by allergen-stimulated blood cells “in vitro” were recorded in the DYAR patients as compared with healthy controls. The significantly increased post-challenge concentrations (p β, IL-2, IL-8, IL-12p70, IL-18, IFN-γ and TNF-α, whereas decreased concentrations of IL-4, IL-6 and IL-17, were released by blood cells stimulated with relevant allergens “in vitro”, as compared both with their pre-challenge concentrations and with the corresponding PBS control values. Conclusions: The profiles of cytokines released by allergen-stimulated peripheral blood cells during the DYAR would suggest an activation of Th1 cells, neutrophils, monocytes and probably also bronchial macrophages, epithelial and endothelial cells and their involvement in the immunologic mechanism(s) underlying the clinical DYAR.

Blood biomarkers of Alzheimer’s disease:important considerations for use in clinical practice

Introduction:Fluid and positron emission tomography(PET)biomarkers that enable the detection of the hallmark proteins of Alzheimer’s disease(AD)(amyloid and tau)have revolutionized our approach to the diagnosis of AD.The evolution of AD diagnostic criteria to include biological characterization(Alzheimer’s Association Working Group,2023)provides an appropriate framework to reduce levels of clinico-pathologic mismatch and improve in-vivo diagnostic accuracy.As the therapeutic landscape for neurodegenerative disease evolves,it is increasingly incumbent on clinicians to provide timely,and pathologically precise diagnoses for patients.However,the expensive and invasive nature of these tests limits their scalability.

The expression of CD40 and CD40L on the surface of peripheral blood mononuclear cells in asthmatic rats and the effect of anti-CD40L McAb on Th1 and Th2 cytokines

Objective： To investigate the expression of CD40 and CD40 ligand （CD4OL） on the surface of peripheral blood mononuclear cells（PBMCs） in asthmatic rats and the effect of anti-CD40L McAb on cytokines of PBMCs. Methods： Flow cytometry and RT-PCR were used to detect the expression of CD40 and CD40L of PBMCs in asthmatic rats. After the PBMCs was treated with anti-CD40L McAb, ELISA was used to detect the IL-4 and IFN-γ levels of culture supernatants. Results： Compared with the normal control group, the expression of CD40 and CD40L of PBMCs in asthmatic rats increased （P 〈 0.05）. Compared with the untreated group, the level of IL-γ and the ratio of IL-4/IFN-γ decreased after the PBMCs was treated with anti-CD40L McAb（P 〈 0.05）. Conclusion： The expression of CD40 and CD40L on the surface of PBMCs in asthmatic rats was up-regulated. Anti-CD40L McAb can rectify the imbalance of Th1 and Th2 cytokines.

Effect on changes of blood coagulation function, cytokines and immune function in patients undergoing laparoscopic radical gastrectomy for gastric cancer

Objective:To explore the changes of coagulation function, cytokines and T lymphocyte in patients undergoing laparoscopic radical gastrectomy for gastric cancer and its clinical significance.Methods: 40 cases of laparoscopic radical gastrectomy for gastric cancer patients and 40 cases of open radical gastrectomy for gastric cancer patients in our hospital were selected to detect and investigate the perioperative coagulation function [APTT (activated partial thromboplastin time), FIB (fibrinogen), and PLT (platelet)], cytokines [CRP (C reactive protein), IL-6 (IL-6) and TNF-alpha (Tumor necrosis factor-alpha)] and T lymphocytes (CD4+, CD8+ and CD4+/CD8+) changes and clinical meaning of patients in the two groups.Results: The coagulation function related indicators, cytokines and T lymphocytes of the two groups before treatment did not change significantly (P>0.05). 1 d after operation, blood coagulation, TNF-alpha, CD4+ and CD4+/CD8+ levels were significantly lower than that before operation in two groups of patients (P<0.05), while IL-6, CRP and CD8+ were significantly higher than that before the operation (P<0.05), and the index change in open group was more obvious. 3 d after surgery, the APTT, IL-6, CRP, CD4+, CD8+ and PLT levels in two group patients were significantly lower than that 1 d after surgery, while FIB, TNF-alpha and CD4+/CD8+ were significantly higher than that 1 d after surgery;blood coagulation index, TNF-alpha and CD4+ and CD4+/CD8+ were significantly lower in the laparotomy group patients than in laparoscopic group, while IL-6, CRP and CD8+ were significantly higher than the laparoscopic group (P<0.05). 5 d after operation, the APTT, TNF-alpha, FIB, CD4+, CD4+/CD8+ and PLT in two groups were significantly higher than that 3 d after surgery (P<0.05), while IL-6, CRP and CD8+ levels were significantly lower than that of 3 d after surgery (P<0.05);blood coagulation index, TNF-alpha and CD4+ and CD4+/CD8+ in the laparotomy group patients were significantly lower than laparoscopic group (P<0.05), while IL-6, CRP and CD8+ were significantly higher than the laparoscopic group (P<0.05).Conclusions: Radical resection of gastric cancer can cause coagulation disorder, inhibit the immune function and inflammatory reaction, and gradually recover with the passage of time;Compared with open surgery, laparoscopic radical gastrectomy have smaller impact on patients and recovery faster.

Meta-analysis of clinical effect of clearing heat and cooling blood on psoriasis and its effect on inflammatory cytokines

Objective:To evaluate the effect of Qingreliangxue method compared with Acitretin Capsules on clinical efficacy of psoriasis and serum inflammatory cytokines.Methods:The computer searches databases such as CNKI,Wanfang,VIP,PubMed,Embase and Cochrane Library.The search time is from the time the library is built until December 2019.According to the criteria for screening and selection of studies,extract data,use risk assessment tools for quality evaluation,and use Revman 5.3 software to perform meta-analysis on the outcome indicators of the included studis.Results:Finally,20 studies were included,with a total of 1592 patients.The analysis results showed that the total effective rate(OR=3.70,95%CI[2.58,5.30],P<0.00001)and cure rate(OR=2.40,95%CI[1.86,3.10],P<0.00001),PASI score(OR=-2.65,95%CI[-3.60,-1.70],P<0.00001),serum inflammatory cytokines(OR=-8.84,95%CI[-10.52,-7.16],P<0.00001),adverse reactions(OR=0.25,95%CI[0.11,0.57],P=0.001)are superior to Acitretin Capsules.Statistics of the top 10 Chinese medicines in clinical used frequency are,in order,habitat,red peony root,paeonol,honeysuckle,comfrey,soil tuckahoe,salvia miltiorrhiza,buffalo horn,heliotrope,angelica.Conclusion:Based on the current evidence,the treatment of psoriasis with clearing heat and cooling blood as the mainstay of Chinese medicine alone or in combination with Acitretin Capsules can better improve the efficacy,and its mechanism may be related to reducing inflammation.Due to the limitation of the included literature,this conclusion needs to be further verified.