Interleukins in liver disease treatment

Cytokines play pleiotropic roles in human health and disease by regulating both innate and adaptive immune responses.Interleukins(ILs),a large group of cytokines,can be divided into seven families,including IL-1,IL-2,IL-6,IL-8,IL-10,IL-12,and IL-17 families.Here,we review the functions of ILs in the pathogenesis and resolution of liver diseases,such as liver inflammation(e.g.,IL-35),alcoholrelated liver disease(e.g.,IL-11),non-alcoholic steatohepatitis(e.g.,IL-22),liver fibrosis(e.g.,Il-17a),and liver cancer(e.g.,IL-8).Overall,IL-1 family members are implicated in liver inflammation induced by different etiologies,such as alcohol consumption,high-fat diet,and hepatitis viruses.IL-2 family members mainly regulate T lymphocyte and NK cell proliferation and activation,and the differentiation of T cells.IL-6 family cytokines play important roles in acute phase response in liver infection,liver regeneration,and metabolic regulation,as well as lymphocyte activation.IL-8,also known as CXCL8,is activated in chronic liver diseases,which is associated with the accumulation of neutrophils and macrophages.IL-10 family members contribute key roles to liver immune tolerance and immunosuppression in liver disease.IL-12 family cytokines influence T-cell differentiation and play an essential role in autoimmune liver disease.IL-17 subfamilies contribute to infection defense,liver inflammation,and Th17 cell differentiation.ILs interact with different type I and type II cytokine receptors to regulate intracellular signaling pathways that mediate their functions.However,most clinical studies are only performed to evaluate IL-mediated therapies on alcohol and hepatitis virus infection-induced hepatitis.More pre-clinical and clinical studies are required to evaluate IL-mediated monotherapy and synergistic therapies.

Association of DNA methylation/demethylation with the functional outcome of stroke in a hyperinflammatory state

Inflammation is closely related to stroke prognosis, and high inflammation status leads to poor functional outcome in stroke. DNA methylation is involved in the pathogenesis and prognosis of stroke. However, the effect of DNA methylation on stroke at high levels of inflammation is unclear. In this study, we constructed a hyperinflammatory cerebral ischemia mouse model and investigated the effect of hypomethylation and hypermethylation on the functional outcome. We constructed a mouse model of transient middle cerebral artery occlusion and treated the mice with lipopolysaccharide to induce a hyperinflammatory state. To investigate the effect of DNA methylation on stroke, we used small molecule inhibitors to restrain the function of key DNA methylation and demethylation enzymes. 2,3,5-Triphenyltetrazolium chloride staining, neurological function scores, neurobehavioral tests, enzyme-linked immunosorbent assay, quantitative reverse transcription PCR and western blot assay were used to evaluate the effects after stroke in mice. We assessed changes in the global methylation status by measuring DNA 5-mc and DNA 5-hmc levels in peripheral blood after the use of the inhibitor. In the group treated with the DNA methylation inhibitor, brain tissue 2,3,5-triphenyltetrazolium chloride staining showed an increase in infarct volume, which was accompanied by a decrease in neurological scores and worsening of neurobehavioral performance. The levels of inflammatory factors interleukin 6 and interleukin-1 beta in ischemic brain tissue and plasma were elevated, indicating increased inflammation. Related inflammatory pathway exploration showed significant overactivation of nuclear factor kappa B. These results suggested that inhibiting DNA methylation led to poor functional outcome in mice with high inflammation following stroke. Further, the effects were reversed by inhibition of DNA demethylation. Our findings suggest that DNA methylation regulates the inflammatory response in stroke and has an important role in the functional outcome of hyperinflammatory stroke.

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.

Data driven analysis reveals prognostic genes and immunological targets in human sepsis-associated acute kidney injury

BACKGROUND:The molecular mechanism of sepsis-associated acute kidney injury(SA-AKI)is unclear.We analyzed co-differentially expressed genes(co-DEGs)to elucidate the underlying mechanism and intervention targets of SA-AKI.METHODS:The microarray datasets GSE65682,GSE30718,and GSE174220 were downloaded from the Gene Expression Omnibus(GEO)database.We identified the co-DEGs and constructed a gene co-expression network to screen the hub genes.We analyzed immune correlations and disease correlations and performed functional annotation of the hub genes.We also performed single-cell and microenvironment analyses and investigated the enrichment pathways and the main transcription factors.Finally,we conducted a correlation analysis to evaluate the role of the hub genes.RESULTS:Interleukin 32(IL32)was identified as the hub gene in SA-AKI,and the main enriched signaling pathways were associated with hemopoiesis,cellular response to cytokine stimulus,inflammatory response,and regulation of kidney development.Additionally,IL32 was significantly associated with mortality in SA-AKI patients.Monocytes,macrophages,T cells,and NK cells were closely related to IL32 and were involved in the immune microenvironment in SA-AKI patients.IL32 expression increased significantly in the kidney of septic mouse.Toll-like receptor 2(TLR2)was significantly and negatively correlated with IL32.CONCLUSION:IL32 is the key gene involved in SA-AKI and is significantly associated with prognosis.TLR2 and relevant immune cells are closely related to key genes.

Interleukin 1βreceptor and synaptic dysfunction in recurrent brain infection with Herpes simplex virus type-1

Several experimental evidence suggests a link between brain Herpes simplex virus type-1 infection and the occurrence of Alzheimer’s disease.However,the molecular mechanisms underlying this association are not completely understood.Among the molecular mediators of synaptic and cognitive dysfunction occurring after Herpes simplex virus type-1 infection and reactivation in the brain neuroinflammatory cytokines seem to occupy a central role.Here,we specifically reviewed literature reports dealing with the impact of neuroinflammation on synaptic dysfunction observed after recurrent Herpes simplex virus type-1 reactivation in the brain,highlighting the role of interleukins and,in particular,interleukin 1βas a possible target against Herpes simplex virus type-1-induced neuronal dysfunctions.

Interleukin-mediated therapies in liver diseases and comorbidity effects

Cytokines like interleukins(ILs)play important roles in inflammation and innate immune.Yang and Zhang carried out an interesting study related to ILs and hepatic diseases.They described the role of ILs in the pathogenesis and resolution of hepatic disorders.The authors summarized alcohol-related liver disease and virus-induced hepatitis,as far as clinical studies a fortiori carried out on ILmediated treatments pertaining to these dysfunctions.This editorial contributes to the review by Yang and Zhang titled,"Interleukins in liver disease treatment",and focuses on therapies mediated by ILs in comorbid liver diseases.The documentary search was conducted on recent pertinent literature,primarily using the Google Scholar and PubMed databases.

Association of serum interleukin-6 with negative symptoms in stable early-onset schizophrenia

BACKGROUND Accumulating evidence suggests that the inflammatory cytokine interleukin-6(IL-6)contributes to the pathophysiology of psychiatric disorders.However,there was no study concerning the relationship between IL-6 concentrations and clinical features in the chronic phase of early-onset schizophrenia(EOS).AIM To investigate the relationship between serum IL-6 concentration and the clinical features of EOS.METHODS We measured serum IL-6 Levels from 74 patients with chronic schizophrenia,including 33 with age at onset<21 years(EOS group)and 41 with onset≥21 years in[adult-onset schizophrenia(AOS)group],and from 41 healthy controls.Symptom severities were evaluated using the Positive and Negative Syndrome Scale(PANSS).RESULTS Serum IL-6 concentrations were higher in both EOS and AOS groups than healthy controls(F=22.32,P<0.01),but did not differ significantly between EOS and AOS groups(P>0.05)after controlling for age,body mass index,and other covariates.Negative symptom scores were higher in the EOS group than the AOS group(F=6.199,P=0.015).Serum IL-6 concentrations in the EOS group were negatively correlated with both total PANSS-negative symptom score(r=-0.389,P=0.032)and avolition/asociality subscore(r=-0.387,P=0.026).CONCLUSION Patients with EOS may have more severe negative symptoms than those with adult-onset schizophrenia during the chronic phase of the illness.IL-6 signaling may regulate negative symptoms and its avolition/asociality subsymptoms among the early-onset chronic schizophrenic patients.

Gossypol acetic acid regulates leukemia stem cells by degrading LRPPRC via inhibiting IL-6/JAK1/STAT3 signaling or resulting mitochondrial dysfunction

BACKGROUND Leukemia stem cells(LSCs)are found to be one of the main factors contributing to poor therapeutic effects in acute myeloid leukemia(AML),as they are protected by the bone marrow microenvironment(BMM)against conventional therapies.Gossypol acetic acid(GAA),which is extracted from the seeds of cotton plants,exerts anti-tumor roles in several types of cancer and has been reported to induce apoptosis of LSCs by inhibiting Bcl2.AIM To investigate the exact roles of GAA in regulating LSCs under different microenvironments and the exact mechanism.METHODS In this study,LSCs were magnetically sorted from AML cell lines and the CD34+CD38-population was obtained.The expression of leucine-rich pentatricopeptide repeat-containing protein(LRPPRC)and forkhead box M1(FOXM1)was evaluated in LSCs,and the effects of GAA on malignancies and mitochondrial RESULTS LRPPRC was found to be upregulated,and GAA inhibited cell proliferation by degrading LRPPRC.GAA induced LRPPRC degradation and inhibited the activation of interleukin 6(IL-6)/janus kinase(JAK)1/signal transducer and activator of transcription(STAT)3 signaling,enhancing chemosensitivity in LSCs against conventional chemotherapies,including L-Asparaginase,Dexamethasone,and cytarabine.GAA was also found to downregulate FOXM1 indirectly by regulating LRPPRC.Furthermore,GAA induced reactive oxygen species accumulation,disturbed mitochondrial homeostasis,and caused mitochondrial dysfunction.By inhibiting IL-6/JAK1/STAT3 signaling via degrading LRPPRC,GAA resulted in the elimination of LSCs.Meanwhile,GAA induced oxidative stress and subsequent cell damage by causing mitochondrial damage.CONCLUSION Taken together,the results indicate that GAA might overcome the BMM protective effect and be considered as a novel and effective combination therapy for AML.

Interleukin 6 and Bone Erosions in Rheumatoid Arthritis in an African Hospital

Introduction: Rheumatoid arthritis (RA) is a chronic, erosive and deforming inflammatory rheumatic disease. In the era of biotherapies and the arrival of biosimilars in sub-Saharan Africa, the objective of this study was to describe plasma IL-6 variations in RA patients at Cité Verte District Hospital (Cameroon). Material and Methods: Descriptive and analytical cross-sectional study from December 1, 2021 to May 31, 2022. We included patients over 18 years old suffering from RA (ACR/EULAR 2010). Patients with an infection were not included. The data collected were age, sex, smoking status, family history, disease duration, disease activity by DAS28, CRP, rheumatoid factor, and plasma level of IL-6. Bone erosion was sought on radiography and ultrasound. Result: We included 31 patients, 25 of whom were women (80.6%). The mean age was 47.27 ± 17.97 years. Disease activity was predominantly moderate (32.3%) and severe (32.3%). Mean IL-6 level was 15.29 ± 2.36 pg/ml (extremes: 11.26 pg/ml and 20.15 pg/ml). IL-6 levels were higher in patients with a history of smoking. Similarly, IL-6 levels were higher in patients with mildly active RA in remission than in moderately and severely active RA. Mean IL-6 levels were significantly higher in patients with erosive RA (16.3 pg/ml VS 14.6 pg/ml). Conclusion: IL-6 levels were significantly elevated in men, weaned smokers and patients with bone erosions.

Clinical Study on the Effectiveness of Xian Fang Huo Ming Yin for Treating Cutaneous Infections and Promoting Wound Healing in Patients with Perianal Abscess

Objective:To explore the effect of the Xian Fang Huo Ming Yin(XFHM)for treating cutaneous infections and promoting wound healing in patients with perianal abscesses.Methods:Sixty-one patients with perianal abscesses who were admitted to our hospital(Xinghua City People’s Hospital)from May 2022 to May 2023 were selected and randomly divided into two groups,a control group(30 cases)and a study group(31 cases).Both groups received surgical treatment.The control group received conventional treatment and warm water fumigation,sitz bath,and surgical dressing change after surgery,while the research group received XFHM based on the control group.XFHM was taken orally and replaced with warm water for fumigation and sitz bathing.Both groups received treatment for 4 weeks but discontinued sitz bathing after 2 weeks.Various clinical indicators between the two groups were compared.Results:The total clinical effective rate and wound recovery rate of the study group were higher than that of the control group.There were differences in the wound pain scores,surrounding tissue edema,and wound secretions at different time points.Both groups experienced wound pain.The scores of wound pain,surrounding tissue edema,and wound secretions of the study group were lower than those of the control group,7 and 14 days after surgery.The serum interleukin 6(IL-6),tumor necrosis factor-alpha(TNF-α)levels,and pH values of the study group were lower than those of the control group 10 days after surgery(P<0.05).Conclusion:The application of XFHM for treating cutaneous infections and promoting wound healing in patients with perianal abscesses improved the treatment outcome,alleviated clinical symptoms,and promoted healing.

下调IL35通过上调自噬相关蛋白表达而抑制肝细胞癌侵袭和迁移

目的探讨白细胞介素35(interleukin 35,IL35)在肝癌中的表达及其临床意义、潜在的分子机制。方法收集手术确诊的肝细胞肝癌和癌旁组织40对。采用RT-qPCR和Western blot检测IL35在肝癌和癌旁组织中的表达,并分析IL35与各临床指标的相关性。Western blot检测IL35在肝癌细胞中的表达。慢病毒转染下调IL35。CCK-8和集落形成检测细胞增殖,Transwell实验检测侵袭和迁移,Western blot检测细胞自噬和EMT相关指标。结果IL35高表达于肝癌组织中(P<0.01);与HL7702肝细胞相比,IL35蛋白表达在Hep3B、Huh7、SMMC7721、Bel7402细胞中升高,且Hep3B表达最高(P<0.01);高表达与血管侵犯相关(P=0.0033);Transwell实验表明下调L35能有效抑制肝癌细胞侵袭和转移(P<0.01);CCK8和平板克隆实验表明,下调IL35能有效抑制肝癌细胞增殖(P<0.01);Western blot结果显示,下调IL35能促进LC3BII、Beclin1表达,抑制p62表达(P<0.01),同时促进E-cadherin表达并抑制N-cadherin、Vimentin的表达(P<0.01)。结论IL35高表达于肝细胞肝癌组织和肝癌细胞中,其表达与肝癌的血管侵犯相关;下调IL35能通过诱导自噬达到抑制肝癌细胞的侵袭和迁移的目的。

Myricetin alleviates ovalbumin-induced allergic rhinitis in mice by regulating Th1/Th2 balance

Objective:To evaluate the effect of myricetin on ovalbumin(OVA)-induced allergic rhinitis in mice.Methods:Mice were sensitized and challenged using OVA(5%,500 mL)intraperitoneally and intranasally,respectively,on an alternative day for 14 days,followed by administration of myricetin(50,100,and 200 mg/kg)till day 21.Nasal symptoms,biochemical parameters,protein expressions,and histopathology were observed.Results:OVA-induced increased nasal symptoms including rubbing,sneezing,and discharge were significantly reduced by myricetin(100and 200 mg/kg)(P<0.05).Myricetin also protected against histamine challenge and attenuated elevated serum immunoglobulin E(IgE;total and OVA-specific),total IgG1,andβ-hexosaminidase levels,as well as leukotriene C4 and interleukins levels in nasal lavage fluid(P<0.05).Western blot analysis showed that myricetin significantly upregulated the protein expression of T-box expressed in T cells,while downregulating the protein expression of GATA binding protein 3,NF-κB,and IκB-α(P<0.05).Additionally,OVA-induced histopathological abberations in the nasal mucosa was markedly ameliorated by myricetin treatment(P<0.05).Conclusions:Myricetin exerts anti-allergic effects against OVAinduced allergic rhinitis via regulating Th1/Th2 balance.

M2 macrophages mediate fibrotic scar formation in the early stages after cerebral ischemia in rats

In the central nervous system, the formation of fibrotic scar after injury inhibits axon regeneration and promotes repair. However, the mechanism underlying fibrotic scar formation and regulation remains poorly understood. M2 macrophages regulate fibrotic scar formation after injury to the heart, lung, kidney, and central nervous system. However, it remains to be clarified whether and how M2 macrophages regulate fibrotic scar formation after cerebral ischemia injury. In this study, we found that, in a rat model of cerebral ischemia induced by middle cerebral artery occlusion/reperfusion, fibrosis and macrophage infiltration were apparent in the ischemic core in the early stage of injury(within 14 days of injury). The number of infiltrated macrophages was positively correlated with fibronectin expression. Depletion of circulating monocyte-derived macrophages attenuated fibrotic scar formation. Interleukin 4(IL4) expression was strongly enhanced in the ischemic cerebral tissues, and IL4-induced M2 macrophage polarization promoted fibrotic scar formation in the ischemic core. In addition, macrophage-conditioned medium directly promoted fibroblast proliferation and the production of extracellular matrix proteins in vitro. Further pharmacological and genetic analyses showed that sonic hedgehog secreted by M2 macrophages promoted fibrogenesis in vitro and in vivo, and that this process was mediated by secretion of the key fibrosis-associated regulatory proteins transforming growth factor beta 1 and matrix metalloproteinase 9. Furthermore, IL4-afforded functional restoration on angiogenesis, cell apoptosis, and infarct volume in the ischemic core of cerebral ischemia rats were markedly impaired by treatment with an sonic hedgehog signaling inhibitor, paralleling the extent of fibrosis. Taken together, our findings show that IL4/sonic hedgehog/transforming growth factor beta 1 signaling targeting macrophages regulates the formation of fibrotic scar and is a potential therapeutic target for ischemic stroke.

Anti-inflammatory natural products modulate interleukins and their related signaling markers in inflammatory bowel disease:A systematic review

This review aims to identify in vivo studies investigating the potential of plant substances and their natural molecules in managing inflammatory bowel disease(IBD).Specifically,the objective is to examine the impact of these substances on interleukins and other key inflammatory signaling markers.Relevant articles published up to December 2022 were identified through a search of the PubMed,Scopus,Web of Science,and Embase databases.The search used keywords including“inflammatory bowel disease”,“medicinal plants”,“natural molecules”,“anti-inflammatory”,and“ulcerative colitis”,and identified 1,878 potentially relevant articles,of which 89 were included in this review after completion of the selection process.This study provides preclinical data on natural products(NPs)that can potentially treat IBD,including ulcerative colitis.The main actions of these NPs relate to their effects on nuclear factor kappa B(NF-κβ),the Janus kinase(JAK)/signal transducer and activator of transcription(STAT)signaling pathway,the regulation of T helper 17/regulatory T cells balance,and oxidative stress.The ability of these NPs to inhibit intestinal inflammation appears to be dependent on lowering levels of the pro-inflammatory cytokines tumor necrosis factor-alpha(TNF-α),interleukin(IL)-1β,and IL-17,via the Jun N-terminal kinase(JNK)1,NF-κβ-p65,and STAT3 pathways.In addition,NPs were shown to reduce oxidative stress and the severity of ulcerative colitis,as well as increase the activity of antioxidant enzymes.These actions suggest that NPs represent a promising treatment for IBD,and potentially have greater efficacy and safety than current treatments.

Nigella sativa oil as a treatment for gingivitis: A randomized active-control trial

Objective: To assess the clinical anti-inflammatory and antimicrobial efficacy of Nigella sativa oil compared with chlorhexidine in patients with gingivitis. Methods: A double-blind, randomized clinical trial was conducted in patients having chronic generalized gingivitis. Patients were randomly assigned to receive Nigella sativa oil(n=18) or chlorhexidine(n=19). The following assessments were made on day 0 and day 15: plaque index, gingival index, gingival IL-6 and IL-18 levels were measured using ELISA, plaque colony-forming units, and alpha-hemolytic Streptococcus strains. Data were analyzed using parametric and non-parametric tests and Fisher’s exact test.Results: Both interventions reduced plaque index and gingival index scores(P<0.000 1). The Nigella sativa oil group was better at lowering IL-6(P=0.007 6) than the chlorhexidine group(P=0.145), although there was no change in IL-18 levels(P>0.05). The post-intervention plaque index and gingival index scores and inflammatory cytokine levels between the two groups were not significantly different. Both interventions caused a significant reduction in the plaque colony-forming units(P<0.000 1), reducing pathogenic bacteria: Streptococcus mitis, Streptococcus oralis, Streptococcus sanguinis, and Streptococcus parasanguinis in the chlorhexidine group(50%)(P=0.103 1), and the Nigella sativa oil group(20%)(P=0.739 5). Conclusions: Nigella sativa oil had anti-inflammatory and antibacterial activities, reducing biofilm formation and disrupting the colonization of pathogenic bacteria essential for the progression of periodontal disease. Nigella sativa oil could offer an alternative therapy for treating gingivitis and may prevent associated systemic diseases and improve overall health outcomes.

Neutralizing peripheral circulating IL1β slows the progression of ALS in a lentivirus-infected OPTN^(E478G)mouse model

Background:Amyotrophic lateral sclerosis(ALS)is irreversible and fatal within 3-5 years,with limited options for treatment.It is imperative to develop a symptom-based treatment that may increase the survival of ALS patients and improve their quality of life.Inflammation status,especially elevated interleukin 1β(IL1β),has been reported to play a critical role in ALS progression.Our study determined that neutralizing circulating IL1βslows down the progression of ALS in an ALS mouse model.Methods:The ALS mouse model was developed by microinjection of lentivirus-carrying OPTN^(E478G)(optineurin,a mutation from ALS patients)into the intra-motor cortex of mice.Peripheral circulating IL1βwas neutralized by injecting anti-IL1βan-tibody into the tail vein.Enzyme-linked immunosorbent assay(ELISA)and real-time polymerase chain reaction(RT-PCR)were carried out to determine the protein and gene expression levels of IL1β.TUNEL assay was used to assess the neural cell death.Immunofluorescent staining of MAP2 and CASP3 was accomplished to evaluate neuronal cell apoptosis.Glial fibrillary acidic protein staining was performed to ana-lyze the number of astrocytes.Rotarod test,grip strength test,balance beam test,and footprint test were conducted to assess the locomotive function after anti-IL1βtreatment.Results:The model revealed that neuroinflammation contributes to ALS progression.ALS mice exhibited elevated neuroinflammation and IL1βsecretion.After anti-IL1βtreatment,ALS mice revealed decreased neural cell death and astrogliosis and gained improved muscle strength and motor ability.Conclusions:Blocking IL1βis a promising strategy to slow down the progression of ALS.

Risk prediction model for distinguishing Gram-positive from Gramnegative bacteremia based on age and cytokine levels:A retrospective study

BACKGROUND Severe infection often results in bacteremia,which significantly increases mortality rate.Different therapeutic strategies are employed depending on whether the blood-borne infection is Gram-negative(G-)or Gram-positive(G+).However,there is no risk prediction model for assessing whether bacteremia patients are infected with G-or G+pathogens.AIM To establish a clinical prediction model to distinguish G-from G+infection.METHODS A total of 130 patients with positive blood culture admitted to a single intensive care unit were recruited,and Th1 and Th2 cytokine concentrations,routine blood test results,procalcitonin and C-reactive protein concentrations,liver and kidney function test results and coagulation function were compared between G+and Ggroups.Least absolute shrinkage and selection operator(LASSO)regression analysis was employed to optimize the selection of predictive variables by running cyclic coordinate descent and K-fold cross-validation(K=10).The predictive variables selected by LASSO regression analysis were then included in multivariate logistic regression analysis to establish a prediction model.A nomogram was also constructed based on the prediction model.Calibration chart,receiver operating characteristic curve and decision curve analysis were adopted for validating the prediction model.RESULTS Age,plasma interleukin 6(IL-6)concentration and plasma aspartate aminotransferase concentration were identified from 57 measured variables as potential factors distinguishing G+from G-infection by LASSO regression analysis.Inclusion of these three variables in a multivariate logistic regression model identified age and IL-6 as significant predictors.In receiver operating characteristic curve analysis,age and IL-6 yielded an area under the curve of 0.761 and distinguished G+from G-infection with specificity of 0.756 and sensitivity of 0.692.Serum IL-6 and IL-10 levels were upregulated by more than 10-fold from baseline in the G-bacteremia group but by less than ten-fold in the G+bacteremia group.The calibration curve of the model and Hosmer-Lemeshow test indicated good model fit(P>0.05).When the decision curve analysis curve indicated a risk threshold probability between 0%and 68%,a nomogram could be applied in clinical settings.CONCLUSION A simple prediction model distinguishing G-from G+bacteremia can be constructed based on reciprocal association with age and IL-6 level.

Biomarkers of Stress and Inflammation in Assessing the Quality of Welfare of Conditioned Vaquejada Horses

In recent decades, the intensity of training and equestrian competitions has significantly increased, thus the assessment of the well-being of the equine athlete has become essential in all equestrian modalities. The aim of this study was to ascertain whether equine athletes submitted to a vaquejada simulation test (VqST), comprised of three races, presented changes in blood biomarkers related to stress and health status. Fourteen healthy Quarter Horses, used as pull horses in this equestrian modality, were evaluated. Ten animals were submitted to the VqST and the remaining four were used as a control group. Blood samples were collected pre-test (during fast), immediately after, and at 1, 4 and 24 hours of recovery. The assessed blood biomarkers included cortisol, interleukin (IL)-6, IL-1β, iron, urea, creatinine, and gamma-glutamyl transferase (GGT) concentrations and results were analyzed using One Way ANOVA (time) with the SigmaStat 13.0 software. No differences between sample times were detected in both groups (p > 0.05) and no differences were found between groups (p > 0.05). The results suggest that all horses were well conditioned for the level of effort imposed by the three vaquejada races. The adaptation to physical exercise may enable the regulation of the acute response to stress in the tissues involved in the exercises, with no differences being observed in stress and health biomarkers, such as IL-6, IL-1β and cortisol. In conclusion, well-conditioned vaquejada horses exhibit a balanced regulation of biological processes, which contributes an increased athletic longevity and better quality of athletic life.

Correlation between Hypovitaminosis D Status and Hyperactivation of IL-6/STAT3 Signaling in Clear Cell Renal Cell Carcinoma

Objective:To analyze serum vitamin D levels in patients with clear cell renal cell carcinoma(ccRCC)by flow cytometry and to investigate the relationship between hypovitaminosis D status and hyperactivation of IL-6/STAT3 signaling in ccRCC.Methods:Eighty patients diagnosed with ccRCC by our oncology department from January 2019 to December 2021 were selected as study subjects,and the control subjects were selected from patients who were receiving health check-up from our hospital(matched according to case group:control group,1:2),with 160 healthy patients.All serum samples collected from the case-control subjects were allowed to stand for 1–2 hours,centrifuged at 3000 rpm for 10 minutes,and stored in a-80°C refrigerator,from which they were removed and thawed to measure 25-hydroxyvitamin D(25(OH)D)and interleukin 6(IL-6)levels.Results:The blood calcium level of patients in the cancer group was significantly lower than that of patients in the non-cancer group,and the difference was statistically significant(P<0.05).The IL-6 level of the cancer group was significantly higher than that of the non-cancer group.In high vitamin D state,the IL-6 level of the non-cancer group was higher than that of the cancer group,and the average concentration of IL-6 in both the cancer group and the non-cancer group was significantly higher in low vitamin D state compared with high vitamin D state(P<0.05);the correlation between hypovitaminosis D status and renal Ki-67 was found to be positive.Conclusion:The results showed that serum IL-6 levels were elevated in the cancer group and circulating serum 25(OH)D levels were negatively correlated with IL-6 levels.In addition,signal transducer and activator of transcription 3(STAT3)signaling in RCC tissues was activated in ccRCC patients and in those with low vitamin D status among the cancer group and was higher than that in those with high vitamin D status.These results suggest that hypovitaminosis D status in ccRCC patients is associated with activated IL-6/STAT3 signaling and the activation of tumor proliferation markers proliferating cell nuclear antigen(PCNA),cyclin D1,and Ki-67.

腰椎间盘突出症患者温针治疗前后血清CGRP及IL-1α的变化及临床意义

目的探讨降钙素基因相关肽(CGRP)及白细胞介素1α(IL-1α)在温针治疗腰椎间盘突出症患者前后血清中的变化及临床意义。方法用酶联免疫吸附测定(ELISA)法检测计入统计的60例腰椎间盘突出症患者在温针治疗前后血清及15例健康对照组血清CGRP及IL-1α水平。观察腰椎间盘突出症患者温针治疗前后McGill疼痛量表各项评分及血CGRP、IL-1α水平变化情况。结果腰椎间盘突出症患者针灸治疗后McGill疼痛量表各项评分均明显下降,差异有统计学意义(P<0.01),血清CGRP及IL-1α水平明显降低,差异有统计学意义(P<0.01)。结论 CGRP及IL-1α可以作为针灸治疗腰椎间盘突出症疗效观察指标,为治疗腰椎间盘突出症保守疗法提供依据。