Interleukin-6 Protein Research Articles

The Levels of Markers of Muscle Damage, Inflammation, and Heat Shock Proteins in Judokas and the Extent of Their Changes during a Special Performance Test at Different Ambient Temperatures

Background: Athletes in combat sports, such as judo, often experience muscle cell damage due to physical and metabolic stress. This study investigates the impact of anaerobic interval exercises involving both upper and lower limbs at different temperatures on physiological indicators. Methods: Fifteen judokas, with an average age of 20.7 ± 2.0 years, participated in the study. They had an average body height of 178 ± 6.3 cm, body mass of 76.3 ± 12.6 kg, VO2max of 43.2 ± 7.8 mL·kg−1, and peak power of 12.1 W·kg−1. The main experiment involved performing five sequences of pulsating exercise on a cycle ergometer for both upper and lower limbs. This was conducted in a thermoclimatic chamber set at temperatures of 21 ± 0.5 °C and 31 ± 0.5 °C with a relative humidity of 50 ± 5%. The sequences alternated pulsations of varying durations and loads between the upper and lower limbs, with a 15 min break following each sequence. Within each sequence, participants underwent four anaerobic limb tests. Biochemical markers, including interleukin-1β (IL-1β), interleukin-6 (IL-6), and heat shock protein 70 (HSP70), were measured using the enzyme-linked immunosorbent assay (ELISA) method before and after exercise, and again at 1, 24, and 48 h post-exercise. Muscle cell damage was evaluated based on lactate dehydrogenase (LDH) activity and myoglobin (Mb) concentration. Results: Both temperature conditions elicited physiological and biochemical responses. Positive correlations were observed between white blood cell count (WBC) and LDH concentration at 21 °C, as well as between WBC and IL-6 at 21 °C. At 31 °C, correlations were seen between WBC and myoglobin, and WBC and LDH. Conclusions: Muscle cell damage was evident under both conditions, as indicated by increased myoglobin levels. These findings offer insights into training strategies and underscore the physiological responses observed in combat sports athletes.

Effect of obesity, lipids and adipokines on allergic rhinitis risk: a Mendelian randomization study

ObjectivesObservational studies suggested that obesity may promote the development of allergic rhinitis. The aim of this study was to explore the association of obesity, lipids and adipokines with this allergic disease at the genetic level using Mendelian randomization strategies. MethodsSummary data for three obesity indicators (such as body mass index), eight lipid indicators (such as triglycerides) and six adipokines (such as interleukin-6 and adipocyte fatty acid-binding protein) were collected, and suitable instrumental variables were extracted from these summary data according to the three main assumptions of Mendelian randomization. Three Mendelian randomization methods (such as inverse variance weighted) were used to detect the casual effect of the above indicators on allergic rhinitis risk. Sensitivity analyses were performed to assess heterogeneity and horizontal pleiotropy. ResultsAfter Bonferroni correction, the inverse variance weighted reported that elevated levels of interleukin-6 and adipocyte fatty acid-binding protein were nominally associated with the decreased risk of allergic rhinitis (OR = 0.870, 95% CI 0.765–0.990, p = 0.035; OR = 0.732, 95% CI 0.551–0.973, p = 0.032). The other Mendelian randomization methods supported these results. Obesity, lipids and other adipokines were not related to this allergic disease. Sensitivity analyses found no heterogeneity and horizontal pleiotropy in the study. ConclusionThe study provided some interesting, but not sufficient, evidence to suggest that interleukin-6 and adipocyte fatty acid-binding protein might play a protective role in the development of allergic rhinitis at the genetic level. These findings should be validated by more research. Level of evidenceThis was a Mendelian randomized study with a level of evidence second only to clinical randomized trials, and higher than cohort and case-control studies.

A six-month low-carbohydrate diet high in fat does not adversely affect endothelial function or markers of low-grade inflammation in patients with type 2 diabetes: an open-label randomized controlled trial

BackgroundWhile a low-carbohydrate diet (LCD) reduces HbA1c in patients with type 2 diabetes (T2D), the associated high intake of fat may adversely affect cardiovascular risk factors. To address this, we examined the effect of a non-calorie-restricted LCD high in fat on endothelial function and markers of low-grade inflammation in T2D over 6 months.MethodsIn an open-label randomized controlled trial, 71 patients with T2D were randomized 2:1 to either a LCD (< 20 E% carbohydrates, 50–60 E% fat) or a control diet (50–60 E% carbohydrates, 20–30 E% fat) for six months. Flow-mediated vasodilation (FMD) and nitroglycerine-induced vasodilation (NID) were assessed by ultrasound in the brachial artery together with plasma interleukin-6 (IL-6) and serum high-sensitivity C-reactive protein (hsCRP) in the participants at baseline (n = 70) and after six months (n = 64).ResultsThe FMD and NID were unaltered in both groups after six months, and there were no between-group differences in change of either FMD (p = 0.34) or NID (p = 0.53) in response to the interventions. The circulating hsCRP and IL-6 levels decreased only in response to LCD (both p < 0.05). However, comparing changes over time with the control diet, the LCD did not reduce either IL-6 (p = 0.25) or hsCRP (p = 0.07) levels. The lack of changes in FMD and NID in response to LCD persisted after adjustment for cardiovascular risk factors.ConclusionA LCD high in fat for six months does not adversely affect endothelial function or selected markers of low-grade inflammation, which suggests that this nutritional approach does not increase the risk of cardiovascular disease.Trial registration ClinicalTrials.gov (NCT03068078).

Effects of glucagon-like peptide-1 receptor agonists on glucose excursion and inflammation in overweight or obese type 2 diabetic patients.

Currently, the lack of comparative studies between weekly and daily formulations of glucagon-like peptide-1 receptor agonists (GLP-1RAs) for glucose excursion is worth investigation. To investigate the effects of weekly and daily formulations of GLP-1RA on glucose excursion and inflammation in overweight and obese patients with type 2 diabetes. Seventy patients with type 2 diabetes mellitus who were treated at our hospital between January 2019 and January 2022 were enrolled in this retrospective analysis. All patients were treated with metformin. We evaluated changes in blood glucose levels and a series of important indicators in patients before and after treatment with either a weekly or daily preparation of GLP-1RA (group A; n = 33 and group B; n = 37). The degree of decrease in the levels of fasting blood glucose, mean blood glucose, mean amplitude of glycemic excursions, total cholesterol, triglycerides, tumor necrosis factor-α, interleukin-6, and high-sensitivity C-reactive protein after treatment in group A was higher than that in group B (P < 0.05), whereas the 2-h postprandial blood glucose levels decreased more so in group B than in group A (P < 0.001). However, there were no statistically significant differences in the levels of glycated hemoglobin, standard deviation of blood glucose, coefficient of variation, absolute mean of daily differences, percentage of time with 3.9 mmol/L < glucose < 10 mmol/L, and high- and low-density lipoproteins between the two groups (P > 0.05). The incidence of adverse reactions was significantly lower in group A than in group B (P < 0.05). The effect of the weekly preparation of GLP-1RA in controlling blood glucose levels in the patients, suppressing inflammation, and reducing adverse reactions was significantly higher than that of the daily preparations, which is worthy of clinical promotion.

Elevated levels of neutrophil related chemokine citrullinated histone H3, interleukin-8 and C-reaction protein in patients with immune checkpoint inhibitor therapy: predictive biomarkers for response to treatment

BackgroundImmune checkpoint inhibitor (ICI) therapy has been used in various tumors. The biomarkers predictive of a response to ICI treatment remain unclear, and additional and combined biomarkers are urgently needed. Secreted factors related to the tumor microenvironment (TME) have been evaluated to identify novel noninvasive predictive biomarkers.MethodsWe analyzed 85 patients undergoing ICI therapy as the primary cohort. The associations between ICI response and all biomarkers were evaluated. A prediction model and a nomogram were developed and validated based on the above factors.ResultsSeventy-seven patients were enrolled in the validation cohort. In the primary cohort, the baseline serum levels of H3Cit, IL-8 and CRP were significantly higher in nonresponder patients. A model based on these three factors was developed, and the “risk score” of an ICI response was calculated with the formula: “risk score” = 3.4591×H3Cit + 2.5808×IL8 + 2.0045 ×CRP– 11.3844. The cutoff point of the “risk score” was 0.528, and patients with a “risk score” lower than 0.528 were more likely to benefit from ICI treatment (AUC: 0.937, 95% CI: 0.886–0.988, with sensitivity 80.60%, specificity 91.40%). The AUC was 0.719 (95% CI: 0.600-0.837, P = 0.001), with a sensitivity of 70.00% and specificity of 65.20% in the validation cohort.ConclusionsA model incorporating H3Cit, IL-8 and CRP has an excellent prediction ability for ICI response; thus, patients with a lower “risk score” selectively benefit from ICI treatment, which may have significant clinical implications for the early detection of an ICI response.

Inflammatory signal transduction pathways induced by prilocaine toxicity in cultured ARPE-19 cells.

Prilocaine (PRL) is a common local anesthetic. Despite the successful use of regional anesthesia for intraocular surgery, there are associated side effects that may affect the retina in case of accidental intravitreal injection. This study examined the signal transduction pathways activated by PRL toxicity and determined the protective role of nitric oxide synthase-2 (NOS2) inhibition in cultured human-derived retinal pigment epithelial cells (ARPE-19). Toxicity analysis was performed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay to detect the toxic dose of PRL and protective effectiveness of asperglaucide (ASP), an NOS2 inhibitor. Nuclear factor kappa B p65 (NF-κB p65), phosphorylated NF-κB p65, phospho-protein kinase B (AKT), NOS2, nitrotyrosine, and cleaved caspase-3 protein levels were evaluated by immunofluorescence staining and/or western blot analysis. Interleukin-6 (IL-6) and nitrated protein levels were quantified using an immunoassay, whereas caspase-3 activity and nitrite/nitrate levels were measured using a fluorometric method. A significant increase in NF-κB p65, and phosphorylated NF-κB p65 and AKT levels due to PRL toxicity was observed. Similarly, IL-6, NOS2, nitrite/nitrate, and nitrotyrosine levels were significantly higher in PRL-treated cells than in control cells. Application of ASP to PRL-treated cells reduced NF-κB p65, and phosphorylated NF-κB p65 and AKT to basal levels. IL-6, NOS2, nitrite/nitrate, and nitrotyrosine levels also considerably decreased following ASP treatment in cells experiencing PRL-induced toxicity. Moreover, the caspase-3-dependent apoptotic pathway was not activated. Our results indicate that ASP could ameliorate PRL-induced activation of NF-κB p65 that led to inflammation in cultured ARPE-19 cells.

Exploring the role of tryptophanyl-tRNA synthetase and associations with inflammatory markers and clinical outcomes in COVID-19 patients: A case-control study

Tryptophanyl-tRNA synthetase (WRS) is a critical enzyme involved in protein synthesis, responsible for charging tRNA with the essential amino acid tryptophan. Recent studies have highlighted its novel role in stimulating innate immunity against bacterial and viral infections. However, the significance of WRS in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains elusive. In this study, we aimed to investigate the complex interplay between WRS, inflammatory markers, Toll-like receptor-4 (TLR-4), and clinical outcomes in coronavirus disease 19 (COVID-19) patients. A case-control investigation comprised 127 COVID-19 patients, carefully classified as severe or moderate upon admission, and 112 healthy individuals as a comparative group. Blood samples were meticulously collected before treatment initiation, and WRS, interleukin-6 (IL-6), and C-reactive protein (CRP) concentrations were quantified using a well-established commercial ELISA kit. Peripheral blood mononuclear cells (PBMCs) were isolated from the blood samples, and RNA was extracted for cDNA synthesis. Semi-quantitative real-time polymerase chain reaction (PCR) was employed to assess the relative expression of TLR-4. COVID-19 patients exhibited elevated levels of WRS, IL-6, CRP, and TLR-4 expression compared to healthy individuals, with the severe group displaying significantly higher levels than the moderate group. Notably, severe patients demonstrated substantial fluctuations in CRP, IL-6, and WRS levels over time, a pattern not observed in their moderate counterparts. Although no significant distinctions were observed in the dynamic alterations of WRS, IL-6, CRP, and TLR-4 expression between deceased and surviving patients, a trend emerged indicating higher IL-6_1 levels in deceased patients and elevated lactate dehydrogenase (LDH) levels in severe patients who succumbed to the disease. This pioneering research highlights the dynamic alterations of WRS in COVID-19 patients, providing valuable insights into the correlation between WRS, inflammatory markers, and disease severity within this population. Understanding the role of WRS in SARS-CoV-2 infection may open new avenues for therapeutic interventions targeting innate immunity to combat COVID-19.

Subjective Social Status and Longitudinal Changes in Systemic Inflammation.

Subjective social status (SSS) refers to a person's perception of their social rank relative to others and is cross-sectionally linked to systemic inflammation independently of objective socioeconomic status. We test the extent to which SSS relates to multiyear changes in inflammation, or if associations differ by race or sex. Healthy adults (N = 331; 30-51 years) completed a baseline visit and 278 participants returned for a second visit 2.85 years later. At both visits, participants underwent a fasting blood draw and completed community (SSSC) and US (SSSUS) versions of the MacArthur Scale. Multiple linear regression analyses examined change in interleukin-6 (IL-6) and C-reactive protein (CRP) predicted by each type of SSS, adjusting for time between visits, sex, race, age, body mass index, smoking, baseline inflammation, and objective socioeconomic status. Additional analyses further adjusted for hopelessness and depressive symptoms. Interactions examined moderations by sex and race. Lower SSSC was longitudinally associated with greater IL-6 independently of all covariates, including education and income (β = -0.06), hopelessness (β = -0.06), and depressive symptoms (β = -0.06). Lower SSSUS was longitudinally associated with greater IL-6 independently of demographic covariates including education and income (β = -0.06), but was slightly attenuated after adjusting for hopelessness (β = -0.06) and depressive symptoms (β = -0.06). There were no associations for CRP or moderation by race or sex. Lower SSS may be associated with greater circulating markers of inflammation over time as suggested by increases in IL-6.

Serum interleukin-6 and high sensitivity C-reactive protein levels and their correlation with the vitiligo disease activity and extent: A cross-sectional study of 58 patients.

Vitiligo is an acquired depigmenting disorder due to the destructive loss of melanocytes, clinically presenting as hypopigmented or depigmented macules and/or patches. Many theories have been proposed to explain its etiopathogenesis among which cell-mediated immunity is one of the crucial links. Estimation of vitiligo activity and extent in a patient is important in tailoring an optimal treatment regimen. Interleukin-6 (IL-6) and high-sensitivity C-reactive protein (HsCRP) are sensitive indicators for systemic inflammation and are found to be relevant in determining vitiligo disease activity. This study was conducted to estimate serum levels of IL-6 and HsCRP in vitiligo patients and to correlate them with the disease activity and extent in order to assess if these serum markers serve as objective indicators of vitiligo disease activity. This was a hospital-based cross-sectional study of 58 vitiligo patients diagnosed clinically irrespective of age, gender, and any ongoing or past treatment. Disease activity and extent were calculated using the vitiligo disease activity (VIDA) score and vitiligo area severity index (VASI), respectively. Serum levels of IL-6 and HsCRP were obtained and their correlation with VIDA and VASI values were statistically analyzed. A weak negative statistically insignificant correlation was found between IL-6 and VIDA (P = 0.092). No correlation was found between VIDA and HsCRP (P = 0.998). A weak positive, statistically insignificant correlation was found between VASI and IL-6 as well as between VASI and HsCRP (P = 0.175 and P = 0.238, respectively). Although statistically insignificant, the patients who were not on immunosuppressive therapy showed higher mean values of IL-6 and HsCRP compared to those who were on immunosuppressive therapy. In contrast to the findings of previous studies, our study found a weak negative correlation between VIDA and IL-6 levels possibly attributable to the difference between the mean levels of IL-6 among the subgroups of patients who were, and were not on immunosuppressive therapy. The VIDA score and HsCRP levels did not show any statistical correlation. However, patients who were not on immunosuppressive therapy showed a higher albeit statistically insignificant mean value of HsCRP. Our observations suggest that any ongoing and/or treatment in the recent past, especially immunosuppressive therapy, and any co-morbidities should be essentially considered while investigating for sensitive serum markers of inflammation as determinants of vitiligo disease activity.

Klebsiella pneumoniae outer membrane vesicles induce strong IL-8 expression via NF-κB activation in normal pulmonary bronchial cells.

Outer membrane vesicles (OMVs) derived from bacteria are known to play a crucial role in the interactions between bacteria and their environment, as well as bacteria-bacteria and bacteria-host interactions.Specifically, OMVs derived from Klebsiella pneumoniae have been implicated in contributing to the pathogenesis of this bacterium.Hypervirulent Klebsiella pneumoniae (hvKp) has emerged as a global pathogen of great concern due to its heightened virulence compared to classical K. pneumoniae (cKp), and its ability to cause community-acquired infections, even in healthy individuals.The objective of this study was to investigate potential differences between hvKp-derived OMVs and cKp-derived OMVs in their interactions with microorganisms and host cells. Four strains of K. pneumoniae were used to produce OMVs: hvKp strain NTUH-K2044 (K1, ST23), hvKp clinical strain AP8555, and two cKP clinical strains C19 and C250. To examine the morphology and size of the bacterial OMVs, transmission electron microscopy (TEM) was utilized. Additionally, dynamic light scattering (DLS) was used to analyze the size characterization of the OMVs.The normal pulmonary bronchial cell line HBE was exposed to OMVs derived from hvKp and cKP. Interleukin 8 (IL-8) messenger RNA (mRNA) expression was assessed using reverse transcription-polymerase chain reaction (RT-PCR), while IL-8 secretion was analyzed using enzyme-linked immunosorbent assay (ELISA).Furthermore, the activation of nuclear factor kappa B (NF-κB) was evaluated using both Western blotting and confocal microscopy. After purification, OMVs appeared as electron-dense particles with a uniform spherical morphology when observed through TEM.DLS analysis indicated that hvKp-derived OMVs from K2044 and AP8555 measured an average size of 116.87±4.95nm and 96.23±2.16nm, respectively, while cKP-derived OMVs from C19 and C250 measured an average size of 297.67±26.3nm and 325±6.06nm, respectively. The average diameter of hvKp-derived OMVs was smaller than that of cKP-derived OMVs.A total vesicular protein amount of 47.35mg, 41.90mg, 16.44mg, and 12.65mg was generated by hvKp-K2044, hvKp-AP8555, cKP-C19, and cKP-C250, respectively, obtained from 750mL of culture supernatant. Both hvKp-derived OMVs and cKP-derived OMVs induced similar expression levels of IL-8 mRNA and protein. However, IL-8 expression was reduced when cells were exposed to BAY11-7028, an inhibitor of the NF-κB pathway.Western blotting and confocal microscopy revealed increased phosphorylation of p65 in cells exposed to OMVs. Klebsiella pneumoniae produces outer membrane vesicles (OMVs) that play a key role in microorganism-host interactions. HvKp, a hypervirulent strain of K. pneumoniae, generates more OMVs than cKP.The average size of OMVs derived from hvKp is smaller than that of cKP-derived OMVs.Despite these differences, both hvKp-derived and cKP-derived OMVs induce a similar level of expression of IL-8 mRNA and protein.OMVs secreted by K. pneumoniae stimulate the secretion of interleukin 8 by activating the nuclear factor NF-κB.

Breathing on chip: Dynamic flow and stretch accelerate mucociliary maturation of airway epithelium in vitro.

Human lung function is intricately linked to blood flow and breathing cycles, but it remains unknown how these dynamic cues shape human airway epithelial biology. Here we report a state-of-the-art protocol for studying the effects of dynamic medium and airflow as well as stretch on human primary airway epithelial cell differentiation and maturation, including mucociliary clearance, using an organ-on-chip device. Perfused epithelial cell cultures displayed accelerated maturation and polarization of mucociliary clearance, and changes in specific cell-types when compared to traditional (static) culture methods. Additional application of airflow and stretch to the airway chip resulted in an increase in polarization of mucociliary clearance towards the applied flow, reduced baseline secretion of interleukin-8 and other inflammatory proteins, and reduced gene expression of matrix metalloproteinase (MMP) 9, fibronectin, and other extracellular matrix factors. These results indicate that breathing-like mechanical stimuli are important modulators of airway epithelial cell differentiation and maturation and that their fine-tuned application could generate models of specific epithelial pathologies, including mucociliary (dys)function.

High-CBD cannabis extracts inhibit the expression of proinflammatory factors via miRNA-mediated silencing in human small intestinal epithelial cells

The incidence of chronic inflammatory disorders and autoimmune diseases is rapidly growing. To date, the COVID-19 pandemic caused by SARS-CoV-2 has killed over 6,209,000 people globally, while no drug has been proven effective for the disease. Screening natural anti-inflammatory compounds for clinical application has drawn much attention. In this study, we showed that high-CBD cannabis extracts #1, #5, #7, #169, and #317 suppressed the levels of expression of proinflammatory cyclooxygenase 2 (COX2) and increased the expression of the anti-inflammatory suppressor of cytokine signaling 3 (SOCS3) in human small intestinal epithelial cells (HSIEC) in TNFα/IFNγ-triggered inflammation. We revealed that these extracts, with the exception of extract #169, also profoundly attenuated induction of proinflammatory cytokines interleukin-6 (IL-6) and/or IL-8 proteins through miR-760- and miR-302c-3p-mediated silencing. The prevalent components in extracts #1 and #7 influenced the levels of IL-8 both individually as well as in combination with each other. However, the high-dose cannabis extracts displayed an inhibitory effect in the growth of HSIEC cells. These results show that our high-CBD cannabis extracts decrease the levels of proinflammatory molecules COX2, IL-6, and IL-8 via transcriptional suppression or miRNA-mediated silencing, highlighting their potential against COVID-19-associated cytokine storm syndrome.

Plasma Interleukin-6 (IL-6), Angiopoietin-2, and C-Reactive Protein Levels Predict Subsequent Type 1 Myocardial Infarction in Persons With Treated HIV Infection.

HIV infection leads to endothelial activation, promoting platelet adhesion, and accelerating atherosclerosis. Our goal was to determine whether biomarkers of endothelial activation and hemostasis/thrombosis were elevated in people with treated HIV (PWH) before myocardial infarction (MI). In a case-control study nested within the CFAR Network of Integrated Clinical Systems (CNICS) cohort, we compared 69 adjudicated cases with type 1 MI with 138 controls matched for antiretroviral therapy regimen. We measured angiopoietin-1, angiopoietin-2 (ANG-2), intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13), von Willebrand factor, C-reactive protein (CRP), interleukin-6 (IL-6), plasminogen activation inhibitor-1, P-selectin, serum amyloid-A, soluble CD14, and apolipoprotein A1 in stored plasma. Conditional logistic regression identified associations with subsequent MI, with and without adjustment for Atherosclerotic Cardiovascular Disease (ASCVD) and Veterans Aging Cohort Study (VACS) scores. Higher IL-6 was associated with MI after adjustment for ASCVD score (adjusted odds ratio [AOR] 1.51, 95% confidence interval [95% CI]: 1.05 to 2.17 per standard-deviation-scaled log 2 increment). In a separate model adjusting for VACS score, higher ANG-2 (AOR 1.49, 95% CI: 1.04 to 2.14), higher CRP (AOR 1.45, 95% CI: 1.06 to 2.00), and higher IL-6 (AOR 1.68, 95% CI: 1.17 to 2.41) were associated with MI. In a sensitivity analysis excluding PWH with viral load ≥400 copies/mL, higher IL-6 remained associated with MI after adjustment for ASCVD score and after adjustment for VACS score. Among PWH, higher levels of plasma IL-6, CRP, and ANG-2 predict subsequent type 1 MI, independent of conventional risk scores. IL-6 had the most consistent associations with type 1 MI, regardless of viral load suppression.

Use of NUTrition Risk in the Critically Ill and Modified NUTrition Risk in the Critically Ill with C-Reactive Protein Scores as a Prognostic Indicator in COVID-19 Patients

Objective: This study aimed to investigate the applicability of the NUTrition Risk in the Critically Ill and modified NUTrition Risk in the Critically Ill with C-reactive protein scores for assessing nutritional risks and predicting outcomes of these critically ill coro- navirus disease 2019 patients. Methods: This retrospective study included 246 adult patients admitted to the intensive care unit between March 15, 2020, and August 15, 2021, diagnosed with coronavirus disease 2019 which was confirmed with real-time-polymerase chain reaction, and who received invasive mechanical ventilation. Treatments in the intensive care unit and clinical outcomes of the patients were recorded. The nutritional risk for each patient was assessed using both the NUTrition Risk in the Critically Ill and the modified NUTrition Risk in the Critically Ill with C-reactive protein scores. If the NUTrition Risk in the Critically Ill and modified NUTrition Risk in the Critically Ill with C-reactive protein scores were ≥6, and the nutritional risk was considered to be high. Results: The median age was 68 (21-93) years, and 61% of them were male. The median duration of invasive mechanical ven- tilation was 9 (1-62) days, the median length of stay in intensive care unit was 15 (1-65) days, and the mortality rate in 28 days was 77.2%. Most of the patients had low nutritional risk according to NUTrition Risk in the Critically Ill score (75.2%) and modi- fied NUTrition Risk in the Critically Ill with C-reactive protein score (69.1%). High NUTrition Risk in the Critically Ill and modified NUTrition Risk in the Critically Ill with C-reactive protein scores were not significantly associated with the duration of invasive mechanical ventilation, length of stay in intensive care unit, and mortality at 28 days. Conclusion: It was shown that NUTrition Risk in the Critically Ill and modified NUTrition Risk in the Critically Ill with C-reactive protein scores were not correlated with the duration of invasive mechanical ventilation, length of stay in intensive care unit, and 28-day mortality in critically ill coronavirus-19 patients. NUTrition Risk in the Critically Ill score was not an appropriate nutrition risk assessment tool as a prognostic marker in patients with severe acute respiratory syndrome coronavirus 2 infection, which is correlated to interleukin-6 and C-reactive protein levels.

Postoperative serum CHI3L1 level is associated with postoperative cognitive dysfunction in elderly patients after hip fracture surgery: A prospective observational study

ObjectivesPostoperative cognitive dysfunction (POCD) is a common postoperative complication in older patients. Chitinase-3-like-1 protein (CHI3L1) is identified as a neuroinflammatory biomarker and impairs cognitive function. This study aimed to evaluate the association between serum levels of CHI3L1 and POCD and explore the levels of interleukin-6 (IL-6), IL-1β and C-reactive protein (CRP) in the elderly after total hip arthroplasty (THA). Patients and methodsA total of 76 elderly patients undergoing THA were enrolled in the prospective observational study. Serum CHI3L1 levels were measured 1 day before and 1 day after surgery and other perioperative factors were also noted. The correlations between mediators of inflammation in the two groups were compared via Spearman correlation coefficients. The receiver operating characteristic (ROC) curves were implemented to analyze the predictive values of serum CHI3L1 and other inflammatory factors for POCD. And factors associated with POCD were analyzed by univariate and multivariate logistics. ResultsPOCD was observed in 31.6% of patients 1 week after surgery. Postoperative serum CHI3L1 levels were higher in POCD patients than in non-POCD patients [1348.26(778.46–1889.77) VS 2322.86(1686.88–2517.35) ng/ml, P < 0.001]. Postoperative serum CHI3L1 level was positively correlated with postoperative IL-6 level (r = 0.284, P = 0.013). Compared with IL-6, IL-1β, and CRP, postoperative CHI3L1 level has the highest predictive value for POCD with the area under the curve (AUC) value of 0.779 according to the ROC curve. By the multivariate logistic regression analysis, elevated postoperative serum CHI3L1 level was found to be an independent risk factor for POCD 1 week after surgery (odds ratio = 1.204, 95% confidence interval = 1.087–1.332, P = 0.001). ConclusionPostoperative elevated serum CHI3L1 level was significantly associated with the incident of POCD, and positively correlated with postoperative IL-6 level in the elderly after THA. This biomarker may have potential utility for further elucidating the etiology of POCD.

Toxicological and histopathological alterations in the heart of young and adult albino rats exposed to mosquito coil smoke

Mosquito coil repellents are well-known indoor air pollutant with significant health concerns. The present study investigated the toxic effects of mosquito coil smoke on the heart of young and adult male rats. The animals were subjected to the smoke for 6 h/day, 6 days/week, for 4 weeks. Within the first hour after lighting the coil, significant amounts of formaldehyde, total volatile organic compounds, and particulate matter (PM2.5 and PM10) were detected. Both exposed ages, particularly the young group, showed a significant increase in the activities of serum aspartate aminotransferase, lactate dehydrogenase, creatine kinase-MB, and the levels of troponin I, myoglobin, Na+ levels, lipid profile, and inflammatory markers (interleukin-6 and C-reactive protein) as well as a significant decrease in K+ levels and cardiac Na–K ATPase activity, indicating development of cardiac inflammation and dysfunction. Furthermore, the toxic stress response was validated by significant downregulation at expression of the detoxifying enzyme cytochrome p450. Histopathological studies in both age groups, especially the young group, revealed cardiomyocyte degeneration and necrotic areas. Moreover, upregulation at the pro-apoptotic markers, caspase3, P53, and cytochrome C expressions, was detected by immunohistochemical approach in heart sections of the exposed groups. Finally, the myocardial dysfunctional effects of the coil active ingredient, meperfluthrin, were confirmed by the docking results which indicated a high binding affinity of meperfluthrin, with Na–K ATPase and caspase 3. In conclusion, both the young and adult exposed groups experienced significant cardiac toxicity changes evidenced by cell apoptosis and histopathological alterations as well as disruption of biochemical indicators.Graphical

The development, validation, and in vivo testing of a high-precision bronchial epithelial lining fluid sampling device.

Analysis of respiratory biomarkers or pharmaceutical drug concentrations in bronchial epithelial lining fluid (bELF) using a high-precision sampling method is crucial for effective clinical respiratory diagnostics and research. Here, we utilized a cellulose matrix as an absorptive probe for bELF sampling, subsequently testing the design of a device and sampling technique in vivo. The absorptive matrix [Whatman® qualitative filter paper (Grade CF-12)] was first tested through tissue-contact experiments on porcine airway tissue. The absorption and elution capacity of the matrix, as well as the laboratory processing and analysis method, was validated with a range of Interleukin-8 (CXCL8) and C-Reactive protein (CRP) stock solutions. Subsequently, the device's design was optimized for universal in-house production and both, safe and efficient sampling. The airway sampling method was then tested in a group of 10 patients with Chronic Obstructive Pulmonary Disease (COPD). For each patient, a bELF sample was obtained using the newly developed bELF probe, as well as a reference 20 mL saline bronchial wash sample. Supernatants were assessed, using an immunoassay, for levels of the pro-inflammatory markers CXCL8, Myeloperoxidase (MPO), and CRP. The bELF samples were compared to bronchial wash. The Whatman® qualitative filter paper (Grade CF-12) bELF probes adhered to porcine airway tissue, softening slightly upon wetting. The material maintained architectural integrity following the removal of the probes, leaving no residual fibers on the porcine airway mucosa. The bELF probe design was optimized for bronchoscopic delivery and in-house production. On average, a fully saturated bELF probe carried 32 μL of protein-rich fluid. The mean return of CXCL8 and CRP from samples collected from a serial dilution series (1, 5, 10, 20 ng/mL) was 69% (range 48%-87%). The bELF probe detected, on average, 7 (MPO), 14 (CRP), and 59 (CXCL8) times higher equivalent inflammatory protein concentrations in the collected bELF probe samples compared to the bronchial wash. The bELF probe is an effective absorptive technology for high-precision bELF sampling without dilution. With a simple in-house production procedure and bronchoscopic sampling technique, this method can be introduced in any bronchoscopic center for a consistent sampling of bELF.

The therapeutic potential of an allosteric non-competitive CXCR1/2 antagonist for diabetic nephropathy.

Diabetic nephropathy is a major consequence of inflammation developing in type 1 diabetes, with interleukin-8 (IL-8)-CXCR1/2 axis playing a key role in kidney disease progression. In this study, we investigated the therapeutic potential of a CXCR1/2 non-competitive allosteric antagonist (Ladarixin) in preventing high glucose-mediated injury in human podocytes and epithelial cells differentiated from renal stem/progenitor cells (RSC) cultured as nephrospheres. We used human RSCs cultured as nephrospheres through a sphere-forming functional assay to investigate hyperglycemia-mediated effects on IL-8 signalling in human podocytes and tubular epithelial cells. High glucose impairs RSC self-renewal, induces an increase in IL-8 transcript expression and protein secretion and induces DNA damage in RSC-differentiated podocytes, while exerting no effect on RSC-differentiated epithelial cells. Accordingly, the supernatant from epithelial cells or podocytes cultured in high glucose was able to differentially activate leucocyte-mediated secretion of pro-inflammatory cytokines, suggesting that the crosstalk between immune and non-immune cells may be involved in disease progression in vivo. Treatment with Ladarixin during RSC differentiation prevented high glucose-mediated effects on podocytes and modulated either podocyte or epithelial cell-dependent leucocyte secretion of pro-inflammatory cytokines, suggesting CXCR1/2 antagonists as possible pharmacological approaches for the treatment of diabetic nephropathy.

Type 2–resistant starch and Lactiplantibacillus plantarum NCIMB 8826 result in additive and interactive effects in diet-induced obese mice

Little is known about how combining a probiotic with prebiotic dietary fiber affects the ability of either biotic to improve health. We hypothesized that prebiotic, high-amylose maize type 2–resistant starch (RS) together with probiotic Lactiplantibacillus plantarum NCIMB8826 (LP) as a complementary synbiotic results in additive effects on the gut microbiota in diet-induced obese mice and other body sites. Diet-induced obese C57BL/6J male mice were fed a high-fat diet adjusted to contain RS (20% by weight), LP (109 cells every 48 hours), or both (RS+LP) for 6 weeks. As found for mice fed RS, cecal bacterial alpha diversity was significantly reduced in mice given RS+LP compared with those fed LP and high-fat controls. Similarly, both RS+LP and RS also conferred lower quantities of cecal butyrate and serum histidine and higher ileal TLR2 transcript levels and adipose tissue interleukin-6 protein. As found for mice fed LP, RS+LP–fed mice had higher colonic tissue TH17 cytokines, reduced epididymal fat immune and oxidative stress responses, reduced serum carnitine levels, and increased transcript quantities of hepatic carnitine palmitoyl transferase 1α. Notably, compared with RS and LP consumed separately, there were also synergistic increases in colonic glucose and hepatic amino acids as well antagonistic effects of LP on RS-mediated increases in serum adiponectin and urinary toxin levels. Our findings show that it is not possible to fully predict outcomes of synbiotic applications based on findings of the probiotic or the prebiotic tested separately; therefore, studies should be conducted to test new synbiotic formulations.

General anesthesia combined with bilateral 2-level erector spinae plane block may accelerate postoperative gastrointestinal function recovery and rehabilitation process in patients undergoing posterior lumbar surgery: A randomized controlled trial

BackgroundThis randomized controlled trial explored whether bilateral 2-level erector spinae plane block could accelerate postoperative gastrointestinal function and rehabilitation in patients undergoing posterior lumbar surgery. MethodsA total of 80 adult patients undergoing posterior lumbar surgery between March 2021 and August 2021 were randomized to either ultrasound-guided bilateral 2-level erector spinae plane block (group E) or not (group C). General anesthesia was routinely performed. The primary outcome was the time of the first flatus after surgery. We also recorded the first food and liquid intake, first off-bed activity, days of hospital stay, and postoperative complications. Postoperative visual analog scale score and opioid consumption were also recorded. A venous blood sample was taken to measure the serum concentration of lipopolysaccharides, c-reactive protein, tumor necrosis factor-alpha, interleukin-6, and blood glucose before induction of anesthesia, immediately after, and 24 and 48 hours after surgery. ResultsSeventy-seven patients, 39 in group C and 38 in group E, finished the trial. Patients in group E had a significantly shorter time to first flatus (16.2 ± 3.2 vs 19.7 ± 3.0 hours, P < .05), earlier liquid intake (1.7 ± 0.2 vs 1.9 ± 0.3 hours, P < .05), earlier food intake (1.9 ± 0.2 vs 2.1 ± 0.3 hours, P < .05), and first off-bed activity (27.9 ± 3.2 vs 31.4 ± 3.3 h, P < .05). Patients in group E had shorter postoperative hospital stay (4.6 [4.2–5.5] d vs 5.4 [4.5–6.3], P < .05). We found that patients in group E had less pain and total sufentanil consumption (129 [120–133] vs 138 [132–147] μg, P < .05) within 24 hours after surgery. At 24 hours after surgery, the serum concentrations of lipopolysaccharides, tumor necrosis factor-alpha, interleukin-6, and C-reactive protein in group E were significantly decreased compared to group C (P < .05). ConclusionBilateral 2-level erector spinae plane block can accelerate gastrointestinal function recovery and shorten the length of hospital stay in patients undergoing open posterior lumbar surgery. The potential mechanism may attribute to the opioids-sparing effects and anti-stress–related anti-inflammatory effects of bilateral 2-level erector spinae plane block.