Interleukin-6 Levels Research Articles

Xuebijing Injection Alleviates the Inflammatory Response in Patients with Venous-Arterial Extracorporeal Membrane Oxygenation: A Prospective Randomized Controlled Study.

Both acute myocardial infarction (AMI) and its salvage treatment, venoarterial-extracorporeal membrane oxygenation (VA-ECMO), may lead to the production of proinflammatory cytokines and further aggravate tissue damage. Xuebijing (XBJ) may modulate cytokine production involved in the inflammatory response. We aimed to determine the efficacy of XBJ in cardiogenic shock patients on VA-ECMO. This was a prospective, randomized trial carried out in an intensive care unit of a tertiary teaching hospital. Patients with cardiogenic shock after acute myocardial infarction undergoing percutaneous coronary intervention (PCI) with VA-ECMO support were randomly divided into a Xuebijing group and a control group. Cytokines, inflammatory factors and left ventricular ejection fraction (LVEF) were compared between the groups. 41 patients were enrolled in the study, with 21 in the Xuebijing group and 20 in the control group. 28 (68.3%) were male, and the average age was 64.71 ± 8.18 years old. There was no difference in APACHEII (acute physiology and chronic health evaluation II) score, LVEF, or cytokine and inflammatory factors collected before extracorporeal membrane oxygenation (ECMO) between the two groups. The levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in the Xuebijing group were lower than those in the control group in the first 24 hours, 48 hours and 72 hours after ECMO (p < 0.05). The LVEF in the Xuebijing group was higher than that of the control group at 48 hours (31.57 ± 3.43 vs. 28.35 ± 4.42, p = 0.013). This trend persisted at 72 hours. The duration of ECMO support in the Xuebijing group was 5.57 ± 2.11 days, which was shorter than that in the control group (p = 0.033). Xuebijing injection can reduce the inflammatory response and improve cardiac function in patients with acute myocardial infarction treated with VA-ECMO to a certain extent. Chinese Clinical Trial Registry (ChiCTR), ChiCTR2100054069, Registered 8, December 2021, https://www.chictr.org.cn/showproj.html?proj=142869.

Astragalus polysaccharide treatment relieves cerebral ischemia‒reperfusion injury by promoting M2 polarization of microglia by enhancing O-GlcNAcylation.

Cerebral ischemia‒reperfusion (I/R) injury seriously threatens the lives of patients. Astragalus polysaccharide (APS) is the main active ingredient of Astragalus membranaceus and has a wide range of pharmacological activities. Here, we aimed to explore the impacts of APS on cerebral I/R injury and its specific mechanisms. We established a cerebral I/R injury model using middle cerebral artery occlusion (MCAO)-treated rats and oxygen glucose deprivation/reoxygenation (OGD/R)-treated BV2 cells. The interleukin 1β (IL-1β), interleukin 6 (IL-6) and interleukin (IL-10) levels were determined using corresponding ELISA kits and RT‒qPCR. The levels of M1 microglial markers (INOS and CD16) and M2 microglial markers (Arg-1 and CD206) were measured by RT‒qPCR. The O-linked N-acetylglucosamine modification (O-GlcNAcylation), O-GlcNAc transfer (OGT) and O-GlcNAc glycosidase (OGA) protein levels were measured by Western blot.Our results showed that APS treatment decreased IL-1β (179.72 ± 9.08 vs. 81.33 ± 6.30) and IL-6 (445.56 ± 33.09 vs. 234.75 ± 27.62) levels and increased IL-10 (41.95 ± 4.18 vs. 86.40 ± 7.16) levels in OGD/R-treated BV2 cells (p < 0.001). In addition, APS promoted the M2 polarization of OGD/R-treated BV2 cells, manifested by an increase in Arg-1 (0.43 ± 0.04 vs. 0.76 ± 0.03) and CD206 (0.36 ± 0.03 vs. 0.65 ± 0.06) and a decrease in INOS (2.84 ± 0.39 vs. 1.56 ± 0.19) and CD16 (4.04 ± 0.36 vs. 1.88 ± 0.09) in OGD/R-treated BV2 cells (p < 0.001). Additionally, APS treatment increased the O-GlcNAcylation and OGT levels in OGD/R-treated BV2 cells, while OGT knockdown reversed the effect of APS in OGD/R-treated BV2 cells and MCAO-treated rats (p < 0.05).Our study demonstrated that APS alleviated cerebral I/R injury by promoting the M2 polarization of microglia by enhancing OGT-mediated O-GlcNAcylation.

Gut microbiotas, inflammatory factors, and mental-behavioral disorders: A mendelian randomization study

BackgroundThe Mendelian randomization approach has emerged as a powerful tool, leveraging genetic variations as natural random experiments to minimize confounding and infer causality with unique advantages. Previous research has highlighted the crucial roles of gut microbiotas and inflammatory factors in mental-behavioral disorders, albeit to varying degrees. However, the precise causal relationship between gut microbiotas and mental-behavioral disorders remains elusive, and the potential role of inflammatory factors as mediators in this process is unclear. MethodsTo investigate the associations between gut microbiotas, inflammatory factors, and mental-behavioral disorders, we pooled data from large-scale genome-wide association studies (GWAS). Our study screened 27 diseases, encompassing nine subtypes of mental-behavioral disorders: neurodevelopmental disorders, eating disorders, sleep disorders, schizophrenia spectrum disorders, stress- and trauma-related disorders, mood and affective disorders, cognitive and executive function disorders, personality and somatization disorders, and addiction disorders. Mendelian randomization(MR) was employed to assess causal relationships between gut microbiotas, inflammatory factors, and these mental-behavioral disorders, with inverse variance weighting (IVW) as the primary statistical method. Furthermore, we explored whether inflammatory factors mediate the relationship between gut microbiotas and mental-behavioral disorders. ResultsHaving investigated the intricate interplay among gut microbiota, inflammatory factors, and mental-behavioral disorders, we have identified nine pivotal inflammatory factors that intricately regulate the progression of eight distinct disease subtypes. Noteworthy among these findings, levels of CC motif chemokine ligand 28 (CCL28) and CC motif chemokine ligand 25 (CCL25) are associated with the progression of attention-deficit/hyperactivity disorder (ADHD), interleukin-18 (IL-18) levels are linked to anorexia, IL-12β levels are related to schizophrenia (SZ) progression, IL-8 levels are associated with manic episodes, and IL-10 and monocyte chemoattractant protein-2 (MCP-2) levels are closely related to enduring personality changes(EPC). Additionally, fibroblast growth factor 19 (FGF19) levels are associated with cognitive disorders, while C-X-C motif chemokine ligand 1 (CXCL1) levels are related to executive functioning. ConclusionGut microbiotas and mental-behavioral disorders have causal relationships, with inflammatory factors mediating the pathway from gut microbiotas to these disorders.

Association between Monocyte-to-Lymphocyte Ratio and Inflammation in Chronic Kidney Disease : A Cross-Sectional Study.

Inflammation plays a key role in chronic kidney disease (CKD). Monocyte-to-lymphocyte ratio (MLR) is a novel inflammatory marker. The purpose of this study was to evaluate the relationship between MLR and inflammation in CKD patients. In total, 1809 subjects were recruited from Wanzhai Town, Zhuhai City, between December 2017 and March 2018 for a cross-sectional survey. Patients were categorized based on the absence (hypersensitive C-reactive protein (hsCRP) level ≦ 3 mg/L) or presence (hsCRP level > 3 mg/L) of inflammation. Logistic regression models and MLR quartiles were used to explore the relationship between MLR and inflammation in CKD patients. Among 1809 subjects, 403 (22.2%) had CKD. Significant differences in systolic blood pressure, estimated glomerular filtration rate, white blood cell (WBC), neutrophil, monocyte, MLR, and Interleukin-6 (IL-6) levels were observed between noninflammatory group and inflammatory group. The highest MLR quartile had higher Scr, WBC, neutrophil, monocyte, IL-6, and hsCRP values and lower eGFR and lymphocyte values. Comparing the lowest quartile of MLR, the OR (95% CI) of inflammation risk in the highest quartile was 2.30 (1.24-4.27) after adjustment for confounding factors. The area under the curve of MLR for predicting inflammation was 0.631. The cutoff point for the MLR was 0.153. A high MLR was significantly and independently associated with inflammation in patients with CKD, making MLR a potential marker for inflammation in this demographic. MLR may also predict the severity of CKD.

Gut microbiome dysbiosis and immune activation correlate with somatic and neuropsychiatric symptoms in COVID-19 patients: Microbiome dysbiosis linked to COVID-19 symptoms.

COVID-19 patients often exhibit altered immune responses and neuropsychiatric symptoms during hospitalization. However, the potential interactions with gut microbiome profiles have not been fully characterized. Here, COVID-19 disease severity was classified as low (27.4%), moderate (29.8%), and critical (42.8%). Fever (66.1%) and cough (55.6%) were common symptoms. Additionally, 27.3% reported somatic symptoms, 27.3% experienced anxiety, 39% had depressive symptoms, and 80.5% reported stress. Gut microbiome profiling was performed using full-length 16S rRNA gene sequencing. Elevated interleukin-6 levels were observed in the most severe cases, indicating systemic inflammation. Reduced gut bacterial diversity was more pronounced in women and obese patients and correlated with higher disease severity. The presence of the genus Mitsuokella was significantly associated with increased physical, stress, anxiety, and depressive symptoms, and Granulicatella with critically ill patients. These findings suggest a link between mental health status, systemic inflammation, and gut dysbiosis in COVID-19 patients, emphasizing the potential of microbiome-targeted therapies to improve recovery and reduce severe complications.

The effect of docosahexaenoic acid (DHA) supplementation on total antioxidant capacity (TAC), superoxide dismutase (SOD), and interleukin-6 levels in underweight pregnant women

HIGHLIGHTS Underweight pregnant women, face an imbalance in energy and protein intake. TAC, SOD, and IL6 with administration of DHA to pregnant women with chronic energy deficiency in the third trimester provide benefits. ABSTRACT Objective: Underweight pregnant women face oxidative stress and inflammation, increasing their risk of intrauterine growth restriction (IUGR) and preterm birth. This study investigates the effects of DHA supplementation on Total Antioxidant Capacity (TAC), Superoxide Dismutase (SOD), and Interleukin-6 (IL-6) in underweight pregnant women, along with the correlation between DHA and these markers. Materials and Methods: This experimental pre-test/post-test study focused on underweight pregnant women in the Made District, Surabaya, Indonesia. Eligible participants were in their second or third trimester, had a BMI below 18.5, and were taking DHA regularly. Exclusion criteria included early pregnancy (gestational age &lt; 14 weeks), BMI above 18.5, irregular DHA intake, and withdrawal from the study. The study ran from July to December 2023, using non-probability sampling to select participants. Blood samples were collected before and after two months of DHA supplementation. Results: Following the intervention, TAC levels demonstrated a noteworthy increase (p &lt; 0.05). SOD levels also exhibited a significant difference (p &lt;0.05), and IL-6 levels showed a significant change (p &lt; 0.05). A strong and positive correlation (r = 0.718) was observed between the increased TAC and SOD levels. DHA influenced both TAC and IL-6, with a significant relationship between TAC and IL-6 (p &lt; 0.01). Furthermore, elevated SOD levels were associated with a decrease in IL-6 levels (p &lt; 0.01). The correlation coefficient value of 0.718 between changes in SOD and TAC indicated a robust positive correlation. Conclusion: The findings suggest that DHA supplementation in underweight pregnant women positively affects oxidative stress and inflammation markers, improving TAC, SOD, and IL-6 levels.

Efficacy of Pulmicort Respules Combined with Azithromycin in the Treatment of Children with Recurrent Respiratory Tract Infection Caused by Mycoplasmal Pneumonia.

Aims/Background The drug treatment of recurrent respiratory tract infection caused by mycoplasma pneumonia (MP) has a complex background, involving the characteristics of pathogens, drug resistance, and multiple treatment methods. This study aimed to analyze the therapeutic effect of pulmicort respules and azithromycin on children with recurrent respiratory tract infection caused by MP. Methods The clinical data of 106 children with recurrent respiratory tract infection caused by MP diagnosed in Huoqiu First People's Hospital from July 2021 to July 2023 were retrospectively analyzed. Based on different therapeutic methods, 56 children treated with azithromycin were included in the reference group, and 50 children treated with pulmicort respules and azithromycin were included in the observation group. The disappearance time of clinical symptoms, levels of inflammatory factors, immunoglobulin levels, and complications in both groups were observed and compared. Results After treatment, the disappearance time of fever, cough, pulmonary rales, and expectoration was shorter in the observation group, compared with the reference group (p < 0.001). No significant difference was observed in levels of tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2), or interleukin-6 (IL-6) between the two groups on the first day of admission (p > 0.05). After 1 week of treatment, the observation group had significantly higher levels of TNF-α, IL-2, and IL-6 compared with the reference group (p < 0.05). No significant difference was observed in levels of immunoglobulin G (IgG), immunoglobulin A (IgA) and immunoglobulin M (IgM) between the two groups on the first day of admission (p > 0.05). After 1 week of treatment, the observation group had significantly lower levels of IgG, IgA, and IgM than the reference group (p < 0.01). This study revealed that the incidence of complications in the observation group was 16.00%, which was significantly lower than the 37.50% in the reference group (p < 0.05). Conclusion In the short-term clinical treatment, the combination application of pulmicort respules and azithromycin can effectively improve the immune function of children with recurrent respiratory tract infection caused by MP and relieve their clinical symptoms.

Lipophilic index of serum phospholipids in patients with type 2 diabetes and atherosclerotic cardiovascular disease: links with metabolic control, vascular inflammation and platelet activation

BackgroundLittle is known about the mechanisms underlying the association of the serum phospholipid lipophilic index (LI) with atherosclerotic cardiovascular disease (ASCVD) in patients with type 2 diabetes (T2D). Therefore, we investigated whether the LI is associated with glucometabolic control, meta-inflammation, thrombin generation, fibrin clot properties, endothelial function and platelet activation in T2D patients with angiographically documented ASCVD.MethodsWe studied 74 T2D patients with ASCVD, aged 65.6 ± 6.8 years, with a median diabetes duration of 10 years and median HbA1c of 7.0%. Serum phospholipid fatty acids (FAs) were measured by gas chromatography. The serum phospholipid LI was calculated as the sum of the products of the proportion (% of total FAs) with the melting points (°C) of each individual FA, divided by the sum of the proportions of all FAs. Levels of HbA1c, insulin, leptin, adiponectin, lipid profiles, inflammatory markers (hsCRP, interleukin-6, TNF-α), Lp-PLA2 (a biomarker of vascular inflammation), endothelial function (sICAM-1, sVCAM-1, FMD, NMD), thrombin generation, fibrin clot properties and platelet activation, measured by light transmission aggregometry with arachidonic acid [AA] and adenosine diphosphate [ADP], were assessed.ResultsPatients with LI > 16.9 °C (median) had higher HbA1c concentrations by 5.9% compared to the remaining subjects (p = 0.035). In this group, HbA1c levels ≥ 7.0% were found more often than in individuals with LI ≤ 16.9 °C (62.2 vs. 35.1%; p = 0.020). Subjects with LI > 16.9 °C had higher levels of TCh by 17.1% (p = 0.012), LDL-Ch by 29.4% (p = 0.003), interleukin-6 by 22.2% (p = 0.031) and Lp-PLA2 by 32.4% (p = 0.040), compared to the remaining patients. Moreover, they had increased maximal platelet aggregation induced by AA (p = 0.045), but not by ADP. Serum phospholipid LI correlated with HbA1c (r = 0.24; p = 0.037), TCh (r = 0.36; p = 0.002), LDL-Ch (r = 0.38; p < 0.001), interleukin-6 (r = 0.27; p = 0.020) and Lp-PLA2 (r = 0.26; p = 0.026). There were no intergroup differences in endothelial function, thrombin generation and fibrin clot properties. Regression analysis showed that HbA1c ≥ 7.0% and serum levels of LDL-Ch, interleukin-6 and Lp-PLA2 were predictors of LI > 16.9 °C in adjusted models.ConclusionsIn well-controlled T2D patients with ASCVD, the higher serum phospholipid LI is associated with worse glucometabolic control, enhanced vascular inflammation and higher platelet reactivity during aspirin treatment at cyclooxygenase-1-selective doses.

Splenic γδ T cells mediate antidepressant and prophylactic actions of arketamine in lipopolysaccharide-induced depression in mice

Arketamine, the (R)-enantiomer of ketamine, exhibits both therapeutic and sustained prophylactic effects in an inflammation-driven model of depression, although the precise mechanisms remain elusive. Given the involvement of γδ T cells in inflammatory processes, this study explored their role in the effects of arketamine. To assess therapeutic outcomes, mice received lipopolysaccharide (LPS:1.0 mg/kg), followed by either arketamine (10 mg/kg) or saline. For prophylactic assessment, arketamine or saline was administered six days prior to LPS exposure. A single dose of LPS (1.0 mg/kg) reduced the proportion of γδ T cells in the spleen but did not affect their levels in the blood, prefrontal cortex, or small intestine. Arketamine mitigated LPS-induced splenomegaly, counteracted the elevation of plasma interleukin-6 levels and the reduction in the proportion of splenic γδ T cells, and alleviated depression-like behavior as assessed by the forced swimming test. Notably, negative correlations were observed between the proportion of splenic γδ T cells and indicators of inflammation and depression. Furthermore, pretreatment with a γδ TCR antibody significantly countered the therapeutic and prophylactic effects of arketamine on LPS-induced changes. These findings highlight a novel role for splenic γδ T cells in inflammation-associated depression and suggest the potential of arketamine as a treatment option. Consequently, γδ T cells may represent a novel therapeutic target for inflammation-related depression. Further studies on the role of γδ T cells in depressed patients with inflammation are warranted.

The Diagnostic Value of 3.0 T Magnetic Resonance Imaging Combined with Carbohydrate Antigen 125 and Human Epididymis Protein 4 in Epithelial Ovarian Cancer

Background: Epithelial ovarian cancer (EOC) is among the top 5 causes of cancer-associated death in women. We explored the diagnostic value of 3.0 T magnetic resonance imaging (MRI) combined with carbohydrate antigen 125 (CA125) and human epididymis protein 4 (HE4) on EOC. Methods: Among 380 ovarian space-occupying patients in this retrospective analysis, 344 were included, 59 were excluded, 25 had incomplete clinical data, and 260 were finally included as the subjects. Patients were classified into the EOC (110 patients with EOC) and N-EOC (150 patients without EOC) groups. The levels of interleukin-6 (IL-6), C-reactive protein (CRP), follicle stimulating hormone (FSH), luteinizing hormone (LH), anti-mullerian hormone (AMH), CA125, and HE4 were determined. The apparent diffusion coefficient (ADC) value and the clinical diagnostic value of MRI, CA125, HE4, and their combination were analyzed. Results: There were significant differences in tumor family history, gravidity, parity, IL-6, CRP, FSH, LH, AMH, and ADC value between EOC and N-EOC patients (all p &lt; 0.05). EOC patients exhibited highly-expressed CA125 and HE4 (p &lt; 0.01). CA125/HE4 expression was correlated with the clinicopathological features of EOC, while the ADC value was correlated with the EOC tumor diameter (all p &lt; 0.05). MRI [area under the curve (AUC) = 0.77], CA125 (AUC = 0.85) and HE4 (AUC = 0.90) had certain diagnostic value for EOC (all p &lt; 0.05). Conclusions: The prevalence of EOC in ovarian space-occupying patients with highly-expressed CA125 and HE4 is higher. MRI combined with CA125 and HE4 has high clinical diagnostic value for EOC.

The proinflammatory status, based on preoperative interleukin-6, predicts postpancreatectomy acute pancreatitis and associated postoperative pancreatic fistula after pancreaticoduodenectomy.

Early predictors of morbidity after pancreaticoduodenectomy (PD) can guide tailored postoperative management. Preoperative inflammatory data in patients who underwent PD remained poorly studied in investigating the clinical significance of predicting postpancreatectomy acute pancreatitis (PPAP) and PPAP-associated postoperative pancreatic fistula (POPF). The clinical data of 467 patients receiving PD between January 2020 and December 2022 were retrospectively reviewed. Preoperative inflammatory data were stratified according to PPAP, and independent risk factors were analyzed. Multivariate logistic regression and subgroup analyses were conducted to compare risk factors of PPAP-associated POPF and non-PPAP-associated POPF. PPAP occurred in 17.6% of patients. The incidence of other complications increased following PPAP. Among the preoperative inflammatory factors, only interleukin-6 (IL-6) increased (P<0.001), leading to a higher incidence of PPAP and POPF (P<0.001; P=0.002). The area under the curve of IL-6 in predicting PPAP was 0.71 (0.65-0.77; P<0.001). Abnormal preoperative IL-6 levels (odds ratio [OR]: 5.01; P<0.001), soft pancreatic texture (OR: 2.15; P=0.007), and pathology (OR: 2.03; P=0.012) were independent risk factors for PPAP. The subgroup analysis showed that increased IL-6 (OR: 1.01; P=0.006) and soft pancreatic texture (OR: 2.05; P=0.033) resulted in a higher risk of PPAP-associated POPF, while increased IL-8 (OR: 1.01; P=0.007), older age (OR: 1.05; P=0.008), and higher body mass index (OR: 1.12; P=0.021) correlated with non-PPAP-associated POPF. PPAP is common after PD; a high preoperative IL-6 level can predict its occurrence, in addition to associated POPF, which could be due to a preoperative proinflammatory status.

Exploring the Link between Periodontal Disease and Systemic Conditions: Implications for Alzheimer’s, Parkinson’s, and Rheumatoid Arthritis

ABSTRACT Background: There is a growing correlation between periodontal disease, a common inflammatory disorder that affects the tissues supporting the teeth, and several systemic diseases. Materials and Methods: Two hundred patients from a tertiary care hospital, ages 50–75, participated in this cross-sectional research. The subjects were split up into four groups: 50 individuals with rheumatoid arthritis, 50 with Alzheimer’s disease, 50 with Parkinson’s disease, and 50 with periodontal disease. To evaluate periodontal condition, including clinical attachment loss and pocket depth, thorough oral exams were performed. Measurements were made of serum biomarkers for inflammation, such as interleukin-6 (IL-6) and C-reactive protein (CRP). Multivariate regression models were used to examine correlations between the severity of periodontal disease and the underlying systemic diseases. Results: In all groups, there were significant relationships between higher levels of indicators of systemic inflammation and the severity of periodontal disease. In comparison to healthy controls (CRP mean value: 2.1 mg/L; IL-6 mean value: 6.4 pg/mL), participants with periodontal disease had higher mean levels of CRP (5.6 mg/L) and IL-6 (mean value: 12.8 pg/mL). Furthermore, compared to those with rheumatoid arthritis, those with Alzheimer’s and Parkinson’s disorders showed higher levels of pocket depth and periodontal attachment loss. Conclusion: In conclusion, the results point to a possible connection between systemic diseases such rheumatoid arthritis, Parkinson’s disease, and Alzheimer’s.

Melatonin attenuates cardiac dysfunction and inflammation in dilated cardiomyopathy via M2 macrophage polarization.

Melatonin is a neuroendocrine hormone that exerts protective effects on the heart. Increasing evidence suggests that macrophage M2-type polarization improves myocardial regeneration and repair. Therefore, this study investigated whether melatonin ameliorates dilated cardiomyopathy (DCM) by modulating M2-type polarization. DCM mice were established by induction with doxorubicin and then treated with melatonin. Cardiac dysfunction was determined by measuring left ventricular ejection fraction (LVEF) and left ventricular internal dimensions at end-diastole and end-systole. Heart injury and fibrosis were determined by hematoxylin and eosin staining and Sirius Red staining, respectively. Serum concentrations of melatonin, tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6) were measured through enzyme-linked immunosorbent assays. M2-type macrophages were analyzed by flow cytometry. Relative mRNA and protein levels were determined by reverse transcription quantitative polymerase chain reaction and western blotting, respectively. Circulating melatonin levels were significantly decreased in DCM mice and were associated with LVEF. Treatment with melatonin markedly ameliorated cardiac dysfunction, improved survival, and alleviated pathological changes and collagen deposition in DCM mice. Furthermore, melatonin-treated DCM mice displayed lower serum and cardiac levels of IL-1β, IL-6, and TNF-α, as well as higher numbers of M2-type macrophages in cardiac tissue, indicating that melatonin treatment could decrease inflammatory responses and facilitate M2 macrophage polarization in DCM mice. Thus, melatonin treatment alleviated cardiac dysfunction and inflammatory responses by promoting M2 macrophage polarization in the DCM mouse model.

A novel chronic obstructive pulmonary disease mouse model induced by intubation-mediated intratracheal co-administration of porcine pancreatic elastase and lipopolysaccharide

BackgroundChronic obstructive pulmonary disease (COPD) is a significant respiratory disorder in humans characterized by persistent airway constriction or obstruction due to chronic bronchitis and pulmonary emphysema. Various methods of inducing COPD in mouse models are frequently used in COPD research; however, these cannot completely reproduce histopathologic lesions. This study aimed to establish a new COPD mouse model that reproduces histopathological lesions closely resembling clinical COPD within a shorter induction time.MethodsThe new strategy involved the co-administration of porcine pancreatic elastase (PPE) and lipopolysaccharide (LPS), with PPE intended to induce pulmonary emphysema and LPS intended to induce chronic bronchitis. Male C57BL/6J mice were administered PPE (8 U/kg) on days 0 and 3 and LPS (400 µg/kg) on days 6, 9, 12, and 15. Each administration was performed using a noninvasive intubation-mediated intratracheal instillation method with a laryngoscope.ResultsPostmortem examination on day 22 revealed that pulmonary emphysema and chronic bronchitis were simultaneously induced in 90.91% of the lung lobes. Molecular studies revealed higher messenger ribonucleic acid (mRNA) expression levels of interleukin-6(IL-6) and matrix metalloproteinase-12(MMP-12) associated with the pathogenesis of COPD.ConclusionA new method was developed to establish a COPD mouse model that displays a more severe representation of the histopathological findings of clinical COPD than previous COPD models. It also reduces the time required for model induction. This newly developed COPD mouse model is expected to be a valuable tool for the pathogenesis and therapeutic research on human COPD.

Changes to inflammatory markers during 5 years of viral suppression and during viral blips in people with HIV initiating different integrase inhibitor based regimens.

Heightened levels of inflammatory markers are linked to increased morbidity/mortality in people with HIV (PWH) and often remain elevated after virologic suppression by antiretroviral therapy (ART). As new combinations of ART become available, an evaluation of their effects on immune activation and inflammation is warranted. Additionally, it remains unknown whether transient increases in viral load ("blips") during ART are associated with increases in inflammation. We utilized cryopreserved samples from treatment-naïve PWH enrolled in two Phase 3 clinical trials investigating the efficacy and safety of bictegravir, emtricitabine and tenofovir alafenamide (B/F/TAF) or dolutegravir, abacavir, and lamivudine (DTG/ABC/3TC) or DTG + F/TAF over a 5-year window (GS-US-380-1489/1490). At week 144, participants were offered the option to switch to open label B/F/TAF for an additional 96 weeks. We measured levels of interleukin-6 (IL-6), C-reactive protein (hsCRP), D-dimer, soluble CD14 (sCD14), and tumor necrosis factor-α receptor 1 (TNFR1) from available baseline, week 24, 48, 144, and 240 samples (B/F/TAF, N=123; DTG/ABC/3TC, N=62; DTG+F/TAF, N=58). Additional samples from PWH who experienced a viral blip (n=44, defined as a single HIV-1 RNA >50c/mL) were also analyzed and paired with the most recent available suppressed sample before the blip. Longitudinal biomarker changes were assessed using a constrained mixed effects linear regression model adjusting for covariates. Baseline demographics and selected laboratory characteristics were similar across groups. Levels of D-dimer, sCD14, and TNFR1 decreased significantly from baseline in all treatment arms, with no significant differences between arms at any timepoint. Biomarker levels also remained stable following ART-switch at week 144. No significant changes in hsCRP or IL-6 were observed versus baseline in any arm at any timepoint. A significant association was observed between sCD14 and increasing viral load (p=0.022) in viral blips; D-dimer also increased with blips in the B/F/TAF arm. Viral suppression was associated with reductions in most inflammatory markers in PWH, with no significant differences among the three ART regimens during the 144-week randomized period. These decreases were sustained after the open label switch to B/F/TAF. Viral blips were associated with increases in monocyte activation (sCD14). Further analysis is needed to confirm these findings and determine the potential impact on clinical outcomes.

CNSC-42. PROGNOSTIC VALUE OF INTERLEUKIN-6 IN PATIENTS WITH GLIOBLASTOMA

Abstract Interleukin-6 (IL-6), a pro-inflammatory cytokine, has been implicated in the invasiveness and progression of glioma. However, the association between serum IL-6 levels at specific time points during treatment and patient prognosis remains unclear. This study was aimed to investigate the prognostic value of IL-6 measured at milestones in the treatment of patients with glioblastoma. Between January 2021 and December 2022, consecutive patients with newly diagnosed glioblastoma were enrolled. Serum IL-6 concentrations were measured at different time points, including preoperative, pre- and post-radiation period, and two-month intervals thereafter. Patients with incomplete data were excluded, and increase of IL-6 values due to the overlapping with systemic infection were also excluded from the analysis. During the study period, 26 patients and 270 IL-6 levels at different time points were evaluated. The median follow-up time was 11 months. Tumor progression was evident in 19 patients (73.1%) and 13 patients (50%) were expired. Preoperative and pre-radiation IL-6 values were available in 20 and 23 patients with the median 5.25 and 4.5 pg/mL, respectively. With the cut-off value of pre-radiation IL-6 at 4.5 pg/mL, high IL-6 group showed significantly worse progression-free survival and overall survival than low IL-6 group (p = 0.027 and 0.008, respectively). However, IL-6 levels at other milestone were not related to the patient prognosis. Serum IL-6 elevation in pre-radiation period is an unfavorable prognostic factor in tumor progression and patient survival. Further research is necessary to validate the prognostic role of IL-6 and explore the underlying mechanisms.

Regulation of ROS metabolism in macrophage via xanthine oxidase is associated with disease progression in pulmonary tuberculosis.

Pulmonary tuberculosis (PTB) exacerbation can lead to respiratory failure, multi-organ failure, and symptoms related to central nervous system diseases. The purpose of this study is to screen biomarkers and metabolic pathways that can predict the progression of PTB, and to verify the role of the metabolic enzyme xanthine oxidase (XO) in the progression of PTB. To explore the biomarkers and mechanisms underlying the progression of PTB, plasma metabolomics sequencing was conducted on patients with severe PTB, non-severe PTB, and healthy individuals. Screening differential metabolites and metabolic pathways that can predict the progression of PTB, and verifying the function and mechanism of action of XO through experiments. The purine metabolism, sphingolipid metabolism, and amino acid metabolism between the three groups differ. In patients with severe PTB, the levels of xanthosine and hypoxanthine are increased, while the levels of D-tryptophan, dihydroceramide and uric acid are decreased. Inhibition of XO activity has been observed to reduce the levels of tumor necrosis factor (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6), as well as to suppress the production of reactive oxygen species (ROS) and the activation of the NF-κB pathway, while also promoting the growth of MTB within cells. D-tryptophan, xanthosine, and dihydroceramide can be utilized as biomarkers for progression of PTB, assisting in the evaluation of disease progression, and XO stands out as a potential therapeutic target for impeding the progression of PTB.

The Predictive Role of Inflammatory Biomarkers and Their Correlation with the Biochemical Profile in Patients with Vasculopathy Undergoing Surgery.

Inflammation is involved in the pathomechanism of vascular diseases. Pro-inflammatory cytokines are important in perioperative monitoring. The aim of the study was the perioperative assessment of biochemical tests and inflammatory markers in patients with vasculopathy, focusing on the identification of subjects prone to complications. The study was performed between 2020 and 2023 at the Clinical County Hospital in Târgu Mureș on enrolled diabetic and non-diabetic patients with vasculopathy and lower limb surgery (amputation or necrectomy). Pre- and postoperative inflammatory markers, biochemical, and hematological tests (n = 62) were performed. Positive correlation was found between preoperative C-reactive protein (CRP) and interleukin-6 (IL-6) levels, and between preoperative triglyceridemia and glycemia/cholesterolemia. Positive correlation was present between pre- and postoperative values of IL-6, tumor necrosis factor-alfa (TNF-α), CRP, and fibrinogen. Preoperative TNF-α values positively correlated with malondialdehyde (MDA) levels, postoperative TNF-α values with transaminase enzymes. Diabetic patients presented higher IL-6 results compared to non-diabetic subjects. We can conclude that dynamic assessment of inflammatory markers is appropriate for monitoring perioperative course. Half of the subjects presented moderately increased preoperative IL-6 levels, and one quarter had critically high values, which might predict prolonged hospitalization. The assessment of oxidative stress, inflammatory markers and biochemical parameters enables the identification of patients prone to complications, so they can benefit from more complex management.

Elevated Interleukin-6 Levels as a Potential Marker of Neonatal Morbidity in Full-term Infants With Polycythemia: A Prospective Study.

To research and show that interleukin-6 (IL-6) and c-reactive protein (CRP), which can be used as infection markers, are also higher among newborns with polycythemia. The study took place in the neonatal intensive care unit of Zekai Tahir Burak Maternity Teaching and Research Hospital. Infants with a gestational age of >37 weeks were included in the study. Infants with chorioamnionitis, perinatal asphyxia, and positive blood culture were excluded from the study. Blood samples were obtained six hours after the delivery from the peripheral vein of the infants for measurements of central hematocrit, blood culture, IL-6, and CRP. Infants with a venous hematocrit value of >65% were grouped as the "polycythemia group," and the ones with a venous hematocrit value of <65% were designated as the "control group." Observation of significantly higher levels of CRP and IL-6 among newborns admitted to the neonatal intensive care unit due to different causes (such as respiratory distress, hypoglycemia, and feeding intolerance), but significantly higher IL-6 levels in newborns with polycythemia. Thirty-five newborns (18 infants in the polycythemia group and 17 infants in the control group) were enrolled in the study. The IL-6 values for the polycythemia group were higher than the upper normal limits (mean ± 2SD, 37.6 ± 55 vs 12 ± 5pg/dL, respectively; P = 0.00). The IL-6 values of the polycythemia group were found to be higher than the IL-6 values of the control group, with a mean ± 2SD of 37.6 ± 55 vs 6.3 ± 3.4pg/dL, respectively; this was significant (P = 0.00). Although the CRP values of the polycythemia group were found to be slightly higher than those of the control group (a mean ± 2SD of 3.06 ± 4.07 vs 1.54 ± 2.21mg/dL, respectively, P > 0.05), this was not significant. This study found a significant and robust statistical correlation between IL-6 and v. Hct values (P = 0.01, rs = 0.641). Contrary to IL-6 levels, however, a meaningful relationship was not found between CRP and v.htc values (P = 0.286; rs = 0.184).

Clinical characteristics of diabetes patients complicated with COVID-19.

Patients with both diabetes and coronavirus disease 2019 (COVID-19) are more likely to experience negative outcomes. This study aimed to identify the risk factors associated with these adverse outcomes that can assist clinicians in implementing suitable treatment strategies to minimize the occurrence of severe complications. A total of 92 patients with diabetes and COVID-19 in the Endocrine Department of Zhejiang Provincial Hospital of Chinese Medicine from December 2022 to February 2023 were enrolled and divided into the recovered group and the transfer to the intensive care unit (ICU) or death group. The clinical characteristics and infection indicators were compared between the 2 groups. Additionally, the patients were further divided into the normal group and the reduction group based on their glomerular filtration rate (GFR), and their clinical characteristics and infection indicators were also analyzed. Compared with the GFR normal group, the GFR reduction group exhibited worse outcomes, higher COVID-19 severity, a higher proportion of mechanical ventilation, and a longer hospital stay. However, there were no significant differences in leukocyte, lymphocyte, and neutrophil counts between these 2 groups. Compared with the recovered group, the transfer to ICU or death group demonstrated an increase in leukocytes and neutrophils, while lymphocytes decreased (P < .05). The C-reactive protein, procalcitonin, interleukin-6, and serum amyloid A levels in the transfer to ICU or death group were significantly higher than those in the Recovered group (P < .05). In addition, C-reactive protein, procalcitonin, and serum amyloid A levels in the GFR reduction group were significantly higher than those in the normal group (P < .05), while interleukin-6 levels were only slightly higher (P > .05). In clinical treatment, it is necessary to monitor infection indicators and GFR closely and intervene in time to reduce the occurrence of adverse events.