IL-6 Concentrations Research Articles

Inflammatory and Oxidant Responses to Arduous Military Training: Associations with Stress, Sleep, and Performance.

Arduous military training frequently consists of prolonged physical activity, sleep disturbance, and stress that increases musculoskeletal injury risk and performance decrements. Inflammatory and oxidative stress responses have been reported in response to arduous training, but with inconsistencies across markers and with under-representation of women. The purpose of the current report was to measure circulating inflammation and oxidative stress responses to military training and to correlate biomarkers with subjective measures of stress and sleep quality as well as military fitness test performance. Candidates undergoing the 10-week Marine Corps Officer Candidate School (OCS; 101 men; 62 women) were monitored, with demographic and questionnaire data collected, and blood drawn before and after OCS. Blood was analyzed for six markers of inflammation and three markers of oxidative stress. Associations between biomarkers and questionnaire and fitness test performance were tested. All measured inflammatory markers as well as plasma antioxidant capacity were elevated following OCS. The inflammatory increase was higher in women for several markers. Sleep disturbance and stress perception were associated with IL-6, IL-10 and CRP concentrations, suggesting that low sleep disturbance and stress perception were associated with low inflammatory load. Additionally, those with the highest inflammation at each time point performed worse on fitness tests than those with low inflammation. Following arduous military training, the circulating environment in a significant portion of officer candidates resembled chronic low-grade inflammation. This circulating inflammatory environment appeared worse with poor sleep, high stress perception, and poor fitness test performance, with utility observed for CRP, IL-6, and IL-10 as biomarkers of these responses. Since inflammation may contribute to musculoskeletal injury and performance decrements, minimizing chronic inflammation during military training should be explored.

In vitro evidence of antioxidant and anti-inflammatory effects of a new nutraceutical formulation explains benefits in a clinical setting of COPD patients.

Background and Aim: Increased oxidative stress within the airways is associated to epithelial damage and amplification of inflammatory responses that in turn contribute to Chronic Obstructive Pulmonary Disease (COPD) progression. This study was aimed to identify whether a new formulation of N-acetylcisteine (NAC), carnitine, curcumin and B2 vitamin could counteract oxidative stress and downstream pro-inflammatory events promoted by cigarette smoke extract (CSE) exposure in primary bronchial epithelial cells (PBEC), both submerged/undifferentiated (S-PBEC) and cultured at the air-liquid interface (ALI-PBEC). Methods: PBEC were exposed to CSE with/without the new formulation or NAC alone and ROS production, IL-8 and IL-6 gene expression and protein release were evaluated. Results: CSE increased ROS, IL-8 and IL-6 gene expression and protein release and the new formulation counteracted these effects. NAC alone was not effective on IL-8 and IL-6 release. The effects of a similar nutraceutical formulation were evaluated in COPD patients treated for six months. The results showed that the treatment reduced the concentration of IL-8 in nasal wash and improved quality of life. Conclusion: The tested formulation, exerting antioxidant and anti-inflammatory effects, can preserve airway epithelial homeostasis and improve clinical symptoms in COPD.

Beneficial Bacteria in the Gut Microbiota May Lead to Improved Metabolic and Immunological Status in Chronic Obstructive Pulmonary Disease.

We included 16 stable COPD patients and 16 healthy volunteer CTLs. The relative abundances of Bifidobacterium spp. (Bf) and Akkermansia muciniphila (Akk) bacteria and the Bacteroidetes and Firmicutes phyla were assessed by qPCR. Pulmonary function was evaluated by spirometry, biochemical parameters by colorimetric methods and plasma cytokine levels by cytometric bead array analysis. The Firmicutes/Bacteroides ratio was related to emergency hospital visits and six-minute walk test (6MWT) results. Furthermore, the relative abundance of Bf was associated with plasma concentrations of glucose, triglycerides, HDL-C and IL-10. In addition, Firmicutes levels and the Firmicutes/Bacteroidetes ratio were associated with the IL-12/IL-10 ratio, while Akk abundance was linked to IL-12 levels. The present findings suggest that the abundance of beneficial bacteria in the GM could influence clinical presentation and immunoregulation in COPD.

The Impact of Liver Steatosis on Interleukin and Growth Factors Kinetics during Chronic Hepatitis C Treatment.

Background/Objectives: Various biological response modifiers play important roles in the immunopathogenesis of chronic hepatitis C (CHC). While serum levels of cytokines and growth factors change with the disease severity and treatment responses, the impact of concomitant liver steatosis on systemic inflammatory response is largely unknown. The aim of this study was to analyze the characteristics and kinetics of serum profiles of interleukins and growth factors in CHC patients with steatotic liver disease (SLD). Methods: Serum concentrations of 12 cytokines (IL-5, IL-13, IL-2, IL-6, IL-9, IL-10, IFN-γ, TNF-α, IL-17A, IL-17F, IL-4 and IL-22) and 6 growth factors (Angiopoietin-2, EGF, EPO, HGF, SCF, VEGF) were analyzed in 56 CHC patients at four time points (baseline, week 4, week 8 and SVR12) with bead-based flow cytometry assay. Results: At baseline, patients with SLD had significantly lower IL-9, IL-10, IL-13 and IL-22 and higher serum concentrations of EGF, VEGF and ANG. In a subgroup of patients with advanced liver fibrosis, SLD was linked with lower serum concentrations of IL-4, IL-5, IL-9, IL-10, IL-13 and IL-22 and higher concentrations of HGH and VEGF. Distinct cytokine kinetics during DAA treatment was observed, and SLD was identified as the main source of variation for IL-5, IL-9, IL-10, IL-13, IL-17A, IL-22, EGF, VEGF and ANG. Patients with SLD at SVR12 had significantly higher VEGF and HGF serum concentrations. Conclusions: SLD is associated with distinct cytokine and growth factor profiles and kinetics during CHC treatment, which might be associated with disease severity and the capacity for liver regeneration and contribute to fibrosis persistence.

NDRG2 Deficiency Exacerbates UVB-Induced Skin Inflammation and Oxidative Stress Damage.

UVB radiation induces inflammatory and oxidative stress responses, contributing to skin damage, yet the underlying mechanisms are not fully understood. N-Myc downstream-regulated gene 2 (NDRG2), an emerging stress-associated gene, remains unexplored in UVB-induced skin injury. In this study, we detected skin NDRG2 expression after UVB irradiation for the first time and further used Ndrg2 knockout mice to clarify the role of NDRG2 in UVB-induced skin injury. Three-month-old male Ndrg2+/+ and Ndrg2-/- mice (16-18g) were exposed to UVB to induce acute skin damage, and then dorsal skin samples were collected for subsequent analyses. UVB-induced skin damage was scored. Western Blot Analysis, immunofluorescence (IF) double labeling, and immunohistochemistry (IHC) were employed to assess NDRG2 expression and/or distribution. The concentrations of TNF-α, IL-6, IL-1β, MPO, MMP8, superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) were quantitatively assessed using enzyme-linked immunosorbent assay (ELISA). Hematoxylin and eosin (HE) staining were employed to determine pathological changes. RNA sequencing and analysis were performed to estimate transcript expression levels and analyze mRNA expression. DESeq2 software was employed to identify differentially expressed genes (DEGs). DEGs were visualized using volcanic and heat maps. Gene Ontology (GO) functions and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were analyzed to identify primary biological functions, metabolic pathways, or signal transduction pathways associated with DEGs. UVB-challenged Ndrg2-/- mice exhibited significantly exacerbated skin damage (erythema, edema, and erosion), neutrophil infiltration, and apoptosis compared to Ndrg2+/+ mice. Furthermore, UVB-challenged Ndrg2-/- mice displayed significantly elevated pro-inflammatory cytokines, myeloperoxidase (MPO), matrix metalloproteinase-8 (MMP8), and reduced antioxidant expression. RNA sequencing identified 1091 significantly differentially expressed genes enriched in inflammation, immune response, and oxidative stress pathways. In conclusion, the deficiency of Ndrg2 markedly exacerbated UVB-induced skin damage by promoting inflammatory responses and inhibiting antioxidant responses. This suggests that stabilizing NDRG2 expression holds promise as a therapeutic strategy for protecting against UVB-induced skin damage.

Effect of Saccharomyces boulardii on Liver Diseases: A Systematic Review.

We aimed to systematize the results of published studies on the use of Saccharomyces boulardii (SB) for the treatment of various liver disorders (CRD42022378050). Searches were conducted using PubMed and Scopus on 1 August 2022. The PubMed search was updated on 15 June 2024. The review included sixteen studies: ten experimental animal studies (EASs) and six randomized controlled trials (RCTs). The CNCM I-745 strain was used in 68.8% of the included studies. SB reduced the severity of many manifestations of cirrhosis, and lowered the Child-Pugh scores in RCT. SB reduced the serum concentrations of TNF-α, IL-1β, IL-6, and IL-4 in animals with metabolic dysfunction-associated steatotic liver disease (MASLD); lowered the serum TNF-α and IL-6 levels in experimental cirrhosis in rats; and reduced the CRP levels in decompensated cirrhosis. The EAS of MASLD revealed that SB reduced liver steatosis and inflammation and lowered the liver expression of genes of TNF-α, IL-1β, interferon-γ, and IL-10. In studies on experimental cirrhosis and MASLD, SB reduced the liver expression of genes of TGF-β, α-SMA, and collagen as well as liver fibrosis. SB reduced the abundance of Escherichia (Proteobacteria), increased the abundance of Bacteroidetes in the gut microbiota, prevented an increase in intestinal barrier permeability, and reduced bacterial translocation and endotoxemia.

Reduced plasma interleukin-6 concentration after transcranial direct current stimulation to the prefrontal cortex

ObjectivesTranscranial direct stimulation (tDCS) targeted to the dorsolateral prefrontal cortex (DLPFC) reduces food intake and hunger, but its effects on circulating factors are unclear. We assessed the effect of repeated administration of tDCS to the left DLPFC (L-DLPFC) on concentrations of pro/anti-inflammatory and appetitive hormone concentrations. Materials and methodsTwenty-nine healthy adults with obesity (12 M; 42±11 y; BMI=39±8 kg/m2) received 3 consecutive inpatient sessions of either anodal or sham tDCS targeted to the L-DLPFC during a period of ad libitum food intake. Fasting plasma concentrations of IL-6, orexin, cortisol, TNF-α, IL-1β, ghrelin, PYY, and GLP-1 were measured before the initial and after the final tDCS sessions. ResultsIL-6 (β=-0.92 pg/ml p=0.03) decreased in the anodal group compared with sham, even after adjusting for kcal intake; there were no changes in other hormones. Mean kcal intake was associated with higher IL-1β and ghrelin concentrations after the ad libitum period (β=0.00018 pg/ml/kcal, p=0.03; β=0.00011 pg/ml/kcal, p=0.02; respectively), but not differ by intervention groups. ConclusionsIL-6 concentrations were reduced following anodal tDCS to the L-DLPFC independent of ad libitum intake. IL-6 concentrations reflect the inflammatory state of adiposity and may affect eating behavior and weight gain. These findings provide evidence of therapeutic benefit of tDCS.

Analysis of the immunomodulatory properties of mycobacterium cell wall fraction on the cytokine production of peripheral blood mononuclear cells of healthy dogs.

Mycobacterium cell wall fraction (MCWF) is derived from nonpathogenic Mycobacterium phlei and is used as an immunomodulatory compound in clinical practice, yet its mode-of-action requires further research. To evaluate the host response to MCWF in canine peripheral blood mononuclear cells (PBMCs) by using enzyme-linked immunosorbent assays (ELISA) and quantitative reverse transcription (qRT)-PCR for assessment of cytokines. Eight healthy Labrador retrievers. PBMCs were isolated from whole blood using density centrifugation. The cells were cultured with different concentrations of MCWF or a potent stimulator of cytokine production, phorbol 12-myristate 13-acetate/ionomycin, or left in cell culture medium for 24, 48 and 72 h. Cytokines were measured by ELISA for interleukin (IL)-4, IL-10 and interferon-gamma (IFN-γ), and by qRT-PCR for IL-4, IL-10, IL-13, IFN-γ, tumour necrosis factor alpha (TNF-α) and transforming growth factor-beta. A significant increase of IL-10 messenger ribonucleic acid (mRNA) was detected at all time points for all concentrations of MCWF (p < 0.05). Protein analysis reflected this finding, with a maximum IL-10 concentration of 300.6 ± 38.3 μg/mL. Compared to the negative control, post-stimulation elevation of IFN-γ mRNA was noted at 24 h with all concentrations of MCWF (p < 0.01), and TNF-α mRNA was increased for 0.5 μg/dL MCWF only at 72 h (p < 0.05). MCWF stimulation of PBMCs results in the elevation of both proinflammatory and regulatory cytokine mRNA. Further research into the role of MCWF as a systemically administered regulatory immunomodulator or adjuvant to allergen-specific immunotherapy should be considered.

Markers of systemic leukocyte activation for assessing acute and chronic systemic inflammation

The phenomenon of systemic leukocyte activation is a component of systemic inflammation (SI), known as the systemic inflammatory response (SIR). Currently, there are hundreds of molecular markers that can serve as criteria for systemic activation, including soluble receptor to IL-2 (sIL-2R) or CD25, β2-microglobulin, and eosinophil cationic protein (ECP). The objective of our study was to assess whether markers of systemic leukocyte activation can be used as criteria for acute and chronic systemic inflammation. Data from 121 patients with acute critical infectious conditions – intensive care patients with sepsis-2 (according to the 2001 consensus, without MODS) and sepsis-3 (2016 consensus, with MODS) – and 136 patients with non-infectious genesis (polytrauma with and without MODS) were analyzed to study acute SI. Additionally, data from 148 patients with immune-inflammatory rheumatic diseases were analyzed to study chronic SI. The reactivity level (RL) was calculated using the author’s method to assess the intensity of SIR. The development of SI was verified based on the measured concentrations of IL-6, IL-8, IL-10, TNFα, CRP, D-dimers, cortisol, myoglobin, and troponin I. Criteria for leukocyte activation phenomenon were sIL-2R 700 units/mL, β2-microglobulin 3000 ng/mL, and ECP 10 ng/mL. Based on the study results, TNFα, ECP, and β2-microglobulin were identified as the most stable indices for dividing groups with and without systemic vasculitis in both acute and chronic diseases. These indices indicate the typical character of systemic leukocyte activation and can be used to assess the intensity of the described phenomenon when integrated into the SI score. However, it is doubtful that these indices can be independently applied as criteria for the complex process of SI and even the SIR phenomenon. This is because the registration of threshold values for two criteria simultaneously during the acute process of SI was only observed in 40.2% of cases, and in chronic processes, it was only observed in 23.7%. These values were comparable to the group without acute SI. Additionally, all three additional criteria were only determined in acute SI in 20.5% of cases and in chronic SI in 3.4%.

Humans seropositive for Trypanosoma cruzi co-infected with intestinal helminths have higher infectiousness, parasitaemia and Th2-type response in the Argentine Chaco

BackgroundThe Gran Chaco ecoregion is a well-known hotspot of several neglected tropical diseases (NTDs) including Chagas disease, soil-transmitted helminthiasis and multiparasitic infections. Interspecific interactions between parasite species can modify host susceptibility, pathogenesis and transmissibility through immunomodulation. Our objective was to test the association between human co-infection with intestinal parasites and host parasitaemia, infectiousness to the vector and immunological profiles in Trypanosoma cruzi-seropositive individuals residing in an endemic region of the Argentine Chaco.MethodsWe conducted a cross-sectional serological survey for T. cruzi infection along with an intestinal parasite survey in two adjacent rural villages. Each participant was tested for T. cruzi and Strongyloides stercoralis infection by serodiagnosis, and by coprological tests for intestinal parasite detection. Trypanosoma cruzi bloodstream parasite load was determined by quantitative PCR (qPCR), host infectiousness by artificial xenodiagnosis and serum human cytokine levels by flow cytometry.ResultsThe seroprevalence for T. cruzi was 16.1% and for S. stercoralis 11.5% (n = 87). We found 25.3% of patients with Enterobius vermicularis. The most frequent protozoan parasites were Blastocystis spp. (39.1%), Giardia lamblia (6.9%) and Cryptosporidium spp. (3.4%). Multiparasitism occurred in 36.8% of the examined patients. Co-infection ranged from 6.9% to 8.1% for T. cruzi-seropositive humans simultaneously infected with at least one protozoan or helminth species, respectively. The relative odds of being positive by qPCR or xenodiagnosis (i.e. infectious) of 28 T. cruzi-seropositive patients was eight times higher in people co-infected with at least one helminth species than in patients with no such co-infection. Trypanosoma cruzi parasite load and host infectiousness were positively associated with helminth co-infection in a multiple regression analysis. Interferon-gamma (IFN-γ) response, measured in relation to interleukin (IL)-4 among humans infected with T. cruzi only, was 1.5-fold higher than for T. cruzi-seropositive patients co-infected with helminths. The median concentration of IL-4 was significantly higher in T. cruzi-seropositive patients with a positive qPCR test than in qPCR-negative patients.ConclusionsOur results show a high level of multiparasitism and suggest that co-infection with intestinal helminths increased T. cruzi parasitaemia and upregulated the Th2-type response in the study patients.Graphical

Efficacy of pentoxifylline for the treatment of bipolar I/II patients with treatment-resistant depression: A proof-of-concept, randomized, double-blind, placebo-controlled trial

BackgroundImmune dysregulation can play a role in depression pathophysiology, and immunological antagonists can improve depressive symptoms in treatment-resistant bipolar depression (TRD) patients according to studies. ObjectiveTo evaluate the anti-depressant effects of the anti-inflammatory drug, pentoxifylline (PTX) in TRD bipolar I/II adult subjects. MethodsThis 12-week, randomized, double-blind, placebo-controlled, parallel-group trial of 60 participants was conducted at Hawler Psychiatric Hospital and Private Clinic in Erbil, Iraq. Participants were confirmed as being qualified for bipolar I/II depression based on DSM-5 criteria. Data were analyzed using modified intent-to-treat analysis. ResultsThere were no significant differences between the two groups in Hamilton Rating Scale for Depression-17 (HAM-D-17) scores (χ2=1.9, P =.48) or a significant time × treatment interaction (χ2=7.1, P=.54). Nevertheless, a significant effect of time was observed with both groups’ reduction in HAM-D-17 scores from the start to the endpoint (χ2= 2.11, P=.002). Besides, a significant time × treatment × CRP interaction was found (χ2=3.1, P=0.016), where there was more reduction in HAM-D-17 score in PTX-treated subjects with CRP> 7.1 mg/L. The response rate difference between PTX and the placebo group did not reach a significance level (χ2=0.84, p=0.43). Furthermore, serum concentrations of TNF-α, CRP, and IL-6 significantly reduced at week 12 in the PTX group (P=.007,.04, and <.001, respectively). ConclusionThe current proof of concept study found that in terms of overall anti-depressant effectiveness in bipolar patients with TRD, PTX is not superior to placebo. However, it may improve depressive mood in a subpopulation of subjects with a higher pretreatment inflammatory profile.

Non-Invasive Detection of Cytokines in Saliva Towards Asthma Phenotyping Using an Electrochemical Sensor

Introduction: Asthma is a complicated and heterogeneous condition of the lungs which is usually associated with the chronic inflammation of the airways. Traditionally, classification of asthma has been based on clinical attributes such as the symptoms observed and response to treatment. However, with the growing understanding of the heterogeneity of asthma as a spectrum with varying underlying causes, asthma phenotyping has been on the horizon. Cytokines are the chemical messengers that play a crucial role in the immune system. They mediate communication between the cells in the immune system and as such have a direct effect on the inflammation process. The role of some cytokines has been established in the pathogenesis of asthma. Due to the involvement of cytokines in the modulation of asthma, they can be excellent target for asthma phenotyping. This is also helpful because identification and quantification of these inflammatory mediators can allow for more precise medicine for more targeted treatment. To aid the identification and quantification of cytokines in the phenotyping of asthma, we have created a customizable (currently for IL-8 and IL-10) multi-marker electrochemical platform for the detection of cytokines non-invasively in saliva. The developed electrochemical platform can detect cytokines rapidly and non-invasively within reported physiological ranges of the given cytokines. Evaluating the presence and quantity of the cytokines will be useful in the phenotyping and treatment plans adopted by physicians.Materials and Methods: The electrochemical sensor consists of 6 multiplexed gold electrodes on a PCB substrate. IL-8 and IL-10 antibodies were immobilized onto the sensor surface using a gold-thiol linker chemistry. Sensor response was evaluated with non- faradaic Electrochemical Impedance Spectroscopy (nf-EIS). Pooled human saliva was spiked with increasing doses of IL-8 and IL-10 in their respective physiological ranges to develop a dose response curve. Spike and recovery experiments were conducted to validate the efficacy of dose response curve.Results and Discussion: Sensor response to both IL-8 and IL-10 spiked doses in pooled saliva showed a dose-dependent response to increasing concentrations of IL-8 and IL-10 respectively as illustrated by the Nyquist plots in Fig.1. The change in impedance with increasing doses of IL-8 and IL-10 in pooled human saliva lends to credence to the establishment of the presence and quantification of cytokines in saliva that can be used by clinicians and scientists alike in the further development of personalized medicine for severe asthmatics unresponsive to traditional asthmatic treatments.Conclusion: This study presents a noninvasive electrochemical sensor for rapid and early detection of cytokines in pooled human saliva towards asthma phenotyping. The sensor exhibits a dose dependent response to IL-8 and IL-10, markers implicated in pathogenesis of asthma. Sensor capability was demonstrated with spike and recovery experiments illustrating the ability of the developed electrochemical sensor to detect and quantify cytokines in human saliva. Figure 1

The role of camel milk as a protective factor on rats infected with indomethacin-induced gastric ulcer

This research was conducted to evaluate the nutritional content of camel milk and the difficulties that accompany them when taken with indomethacin. The results observed that camel milk is a rich source of nutritional values and antioxidants. The biological experimental was divided into six groups. The first group was control negative, and the groups G2, G3, G4, and G5 had orally one dose of indomethacin (30 mg/kg body weight) to induce ulcers. The G2 was considerably a positive control, and the groups G3, G4, and G5 had orally 5, 10, and 15 mL/kg body weight daily camel milk. The results observed that camel milk markedly raised concentrations of enzymatic antioxidants while concurrently lowering malondialdehyde levels in comparison to the positive group. However, rats taken orally 15 mL/kg camel milk showed significantly lower serum IL-6 and tumor necrosis factor-α concentration compared to 5 and 10 mL/kg camel milk. Rats given indomethacin showed a significant decrease in cyclooxygenase (COX-2) and prostaglandin E2 (PGE2) levels and also a significant increase in cytochrome P450 reductase activity. These results were based on the measurements of cyclooxygenase activity, PGE2 concentration, and cytochrome P450 reductase activity in the gastric tissues. The results from macroscopic examination and histopathological examination of gastric ulcers in normal and treated rats groups with camel milk confirmed the above results by serum and gastric tissue. Therefore, camel milk has a potent ulcer-healing impact on gastrointestinal injury caused by indomethacin. The potential cytoprotective mechanism and antioxidant characteristics of camel milk may be responsible for its antiulcer efficacy.

Effects of Acremonium terricola Culture on Lactation Performance, Immune Function, Antioxidant Capacity, and Intestinal Flora of Sows.

This study aimed to determine the effects of different doses of Acremonium terricola culture (ATC) on lactation performance, immune function, antioxidant capacity, and intestinal flora of sows. Forty-five Landrace sows (3-6 parity) were randomly assigned to the following three treatments from 85 days of gestation to 21 days after farrowing: a control diet (CON, basal diet), a low-dose Acremonium terricola culture diet (0.2% ATC, basal diet + 0.2% ATC), and a high-dose Acremonium terricola culture diet (0.4% ATC, basal diet + 0.4% ATC). Compared with the CON group, the supplementation of 0.2% ATC increased the average daily milk yield of sows by 4.98%, increased milk fat, total solids, and freezing point depression on day 1 postpartum (p < 0.05), increased serum concentration of Triiodothyronine, Thyroxin, and Estradiol on day 21 postpartum (p < 0.05). Compared with the CON group, the supplementation of 0.4% ATC increased the average daily milk yield of sows by 9.38% (p < 0.05). Furthermore, the supplementation of 0.2% ATC increased serum concentration of IgG, IgM, and IFN-γ, CD4 on day 1 postpartum (p < 0.05) and increased serum concentration of immunoglobulin A ( IgA), immunoglobulin G (IgG), immunoglobulin M ( IgM), complement 3 (C3), cluster of differentiation 4 (CD4), cluster of differentiation 8 (CD8), interferon-γ (IFN-γ) on day 21 postpartum (p < 0.05), while the supplementation of 0.4% ATC reduced serum concentration of IL-2 on day 21 postpartum (p < 0.05). Moreover, the supplementation of 0.4% ATC significantly increased serum concentration of catalase (CAT) (p < 0.05). Additionally, the supplementation of ATC affected the relative abundance of the intestinal flora at different taxonomic levels in sows and increased the abundance of beneficial bacteria such as in the norank_f__Eubacterium_coprostanoligenes group, Eubacterium_coprostanoligenes group, and Lachnospiraceae_XPB1014 group of sows, while reducing the abundance of harmful bacteria such as Phascolarctobacterium and Clostridium_sensu_stricto_1. These data revealed that the supplementation of ATC during late gestation and lactation can improve lactation performance, immune function, antioxidant capacity, and the gut microbiota. Compared with supplementation of 0.4% ATC, 0.2% ATC enhances the levels of thyroid-related hormones, specific antibodies, and cytokines in serum, promotes the diversity of beneficial gut microbiota, beneficial bacteria in the intestine, reduces the population of harmful bacteria, and thereby bolsters the immunity of sows. Hence, 0.2% ATC is deemed a more optimal concentration.

Association of Acute Systemic Inflammation with Patient-Centric Postoperative Pulmonary Complications After Elective Cardiac Surgery.

Postoperative pulmonary complications (PPCs) occur frequently after cardiac surgery. Absolute postoperative values of biomarkers of inflammation (interleukin [IL]-6, IL-8, and tumor necrosis factor-alpha [TNF-α]) and alveolar epithelial injury (soluble receptor for advanced glycation end-products [sRAGE]) have been associated with hypoxia and prolonged ventilation. However, relationships between these biomarkers and PPCs, contextualized to preoperative inflammation and perioperative lung injury risk factors, are uncertain. We aimed to determine associations between perioperative increases in biomarkers of inflammation and alveolar epithelial injury with a patient-centric PPC definition in adult cardiac surgical patients, accounting for the influence of intraoperative risk factors for lung injury. Adults undergoing elective cardiac surgery were eligible for this observational cohort study. Blood concentrations of IL-6, IL-8, TNF-α, and sRAGE were collected after anesthesia induction (baseline) and on postoperative day 1 (POD 1). The primary outcome was the occurrence of moderate or severe PPCs, graded using a validated scale, in POD 0 to 7. We estimated the association between POD 1 IL-6, IL-8, TNF-α, and sRAGE concentrations and moderate/severe PPC presence using separate logistic regression models for each biomarker, adjusted for baseline biomarker values and risk factors for postoperative lung injury (age, baseline PaO2/FiO2, left ventricle ejection fraction [LVEF], procedural type, cardiopulmonary bypass duration, and transfusions). Covariables were chosen based on relevance to lung injury and unadjusted between-group differences among patients with versus without PPCs. The secondary outcome was postoperative ventilation duration, which was log-transformed and analyzed using linear regression, adjusted using the same variables as the primary outcome. We enrolled 204 patients from 2016 to 2018. Biomarkers were analyzed in 2023 among 175 patients with complete data. In adjusted analyses, POD 1 IL-8 and IL-6 were significantly associated with moderate/severe PPCs. The odds ratio (OR) for developing a PPC for every 50 pg/mL increase in POD 1 IL-8 was 7.19 (95% confidence interval [CI], 2.13-28.53, P = .003) and 1.42 (95% CI, 1.13-1.93, P = .01) for every 50 pg/mL increase in POD 1 IL-6. In adjusted analyses, postoperative ventilation duration was significantly associated with POD 1 sRAGE; each 50 pg/mL increase in sRAGE was associated with a 25% (95% CI, 2%-52%, P = .03) multiplicative increase in hours of ventilation. TNF-α was not significantly associated with PPCs or ventilation duration. Acute systemic inflammation is significantly associated with PPCs after elective cardiac surgery in adults when taking into consideration preoperative inflammatory burden and perioperative factors that may influence postoperative lung injury.

Targeting MCM2 activates cancer-associated fibroblasts-like phenotype and affects chemo-resistance of liposarcoma cells against doxorubicin.

Liposarcoma is one of the most common soft tissue malignancies. We previously discovered upregulation of minichromosome maintenance 2 (MCM2) expression in liposarcoma tissues. Hereon, we attempt to clarify the biological influence and mechanisms of MCM2 in liposarcoma. The mRNA level of MCM2 expression was detected through the use of quantitative real-time PCR. Immunohistochemistry staining and western blot were employed to detect protein expression of MCM2. The protein expression of fibroblast-activation protein and α-smooth muscle actin was examined by immunofluorescence. Protein concentrations of interleukin (IL)-6, transforming growth factor β, and IL-8 were measured via ELISA. Furthermore, liposarcoma cell viability was assessed through cell counting kit-8 assay, and liposarcoma cell invasiveness and migration were evaluated through transwell assay. For assessing proliferation and apoptosis of liposarcoma cells, colony formation assay and flow cytometry were used. For constructing a mouse tumor model, SW872 cells were introduced into mouse flank via subcutaneous injection. MCM2 expression was boosted in liposarcoma tissues and cells when compared with the controls. MCM2-activated cancer-associated fibroblasts (CAFs)-like phenotype, presenting as increased fibroblast-activation protein expression, α-smooth muscle actin expression, cell migration, IL-6 concentration, IL-8 concentration, and transforming growth factor β concentration. Functional experiments indicated that MCM2-activated-CAFs facilitated proliferation, migration, and invasion of liposarcoma cells. Additionally, 1 μM doxorubicin treatment could not affect proliferation and apoptosis of liposarcoma cells, whereas combined use of MCM2 knockdown and 1 μM doxorubicin evidently repressed cell proliferation and promoted apoptosis. In vivo, silencing of MCM2 impaired tumor growth in mice. MCM2 overexpression promoted CAFs formation and tumor progression, showing potential value in treatment of liposarcoma.

Effects of taurine on the growth performance, diarrhea, oxidative stress and intestinal barrier function of weanling piglets.

Oxidative damage resulting from weaning stress significantly impacts the growth performance and health status of piglets. Taurine, a dietary antioxidant with diverse functions, was investigated in this study for its protective role against weaning stress-induced oxidative damage and its underlying mechanism. Forty 28-day-old male castrated weaned piglets were randomly assigned to four groups. The control group received the basal diet, while the experimental groups were fed the basal diet supplemented with 0.1, 0.2%, or 0.3% taurine over a 28-day period. In vitro, H2O2 was utilized to induce oxidative damage to the jejunal mucosa of piglets via IPEC-J2 cells. The results demonstrated that taurine supplementation reduced the incidence of diarrhea in piglets compared to that in the control group (p < 0.05); the addition of 0.2 and 0.3% taurine led to increased average daily gain and improved feed conversion efficiency in weaned piglets, showing a linear dose-response correlation (p < 0.05). Taurine supplementation at 0.2 and 0.3% enhanced the activities of serum CAT and GSH-Px while decreasing the levels of serum NO, XOD, GSSG, and MDA (p < 0.05). Moreover, it significantly elevated the levels of GSS, Trx, POD, complex I, mt-nd5, and mt-nd6, enhancing superoxide anion scavenging capacity and the hydroxyl-free scavenging rate in the livers of weaned piglets while reducing NO levels in the liver (p < 0.05). Additionally, 0.2 and 0.3% taurine supplementation decreased serum IL-6 levels and elevated the concentrations of IgA, IgG, and IL-10 in weaned piglets (p < 0.05). The levels of occludin, claudin, and ZO-1 in the jejunum mucosa of weaned piglets increased with 0.2 and 0.3% taurine supplementation (p < 0.05). In IPEC-J2 cells, pretreatment with 25 mM taurine for 24 h enhanced the activities of SOD and CAT; reduced the MDA content; upregulated the mRNA expression of various genes, including ZO-1, occludin, claudin-1, Nrf2, and HO-1; and reversed the oxidative damage induced by H2O2 exposure (p < 0.05). Overall, the findings suggest that the inclusion of 2 and 3% taurine in the diet can enhance growth performance, reduce diarrhea rates, ameliorate oxidative stress and inflammation, and promote intestinal barrier function in weaned piglets.

Dexamethasone administration restored growth in dairy calves exposed to heat stress

Recent evidence indicates that the heat stress loss on the growth performance of calves is associated with the diversion of nutrients to control enteritis and systemic inflammation. In this study, we investigated the impact of heat stress on markers of inflammation, feed use-efficiency, and growth of dairy calves. We hypothesized that dexamethasone, which is known for its immunosuppressive and anti-inflammatory properties, would reduce inflammation and restore the growth of calves exposed to heat stress. Thirty-two Holstein bull calves (body weight (BW) 68.5 ± 1.37 kg; age 3.5 ± 0.5-week-old; mean ± SD) were housed in individual pens in climate-controlled rooms at constant ambient temperature and allowed to adjust to facilities for 5 d before the start of treatments. Calves were randomly assigned to one of 4 treatments (n = 8/treatment) in a 2 × 2 factorial arrangement of environment (ENV, thermoneutral or heat stress) and intervention (INT, saline or dexamethasone) imposed for 5 d as follow: 1) thermoneutral (constant ambient temperature of 20°C 24 h/d) and administration of saline, 2) thermoneutral (constant ambient temperature of 20°C 24 h/d) and administration of dexamethasone, 3) cyclic heat stress (40°C ambient temperature, from 0800 to 1900 h/d) and administration of saline, 4) cyclic heat stress (40°C ambient temperature, from 0800 to 1900 h/d) and administration of dexamethasone. Dexamethasone (0.05 mg/kg BW), or saline (1.2 mL) was administered intramuscularly on d 1 and 3. Upon completion of treatments, calves were euthanized on d 5 to obtain jejunum mucosa samples. Commercial milk replacer, starter grain, and water were offered, and intake was monitored daily. Rectal temperature and respiratory rate were monitored 3 times daily. Blood samples were collected on d 1, 3, and 5 to determine serum pro-inflammatory cytokine concentrations. A section of the jejunum was collected and snap-frozen to determine the concentration of pro-inflammatory markers. Statistical analyses included a mixed model, fixed effects of ENV, INT, consecutive measurements taken over time (d, h, or both), replica, and random effects of calf and error (SAS version 9.4, SAS Institute Inc., Cary, NC). The measurements collected immediately before treatment allocation were included as covariates in the model. An ENV effect showed that heat stress increased rectal temperature (38.72 vs. 39.21°C), respiratory rate (36 vs. 108 breaths/min), and water intake (3.2 vs. 6.6 L/d). The treatments did not affect dry matter intake. An ENV × INT interaction showed that heat stress with saline decreased average daily gain (ADG) by 35% and tended to decrease feed use-efficiency by 36%, but the use of dexamethasone to treat heat stress restored ADG and feed use-efficiency comparable to their basal levels. An ENV × INT interaction revealed that heat stress with saline increased jejunal interleukin (IL)-6 concentration 2-fold, but dexamethasone treatment of heat stress restored jejunal IL-6 concentration to basal levels. The bioenergetic cost of the heat stress-immune pro-inflammatory response ranged between 1.18 and 1.50 Mcal of ME. Overall, the administration of dexamethasone reduced the jejunal concentration of a pro-inflammatory marker and restored the heat stress-associated reduction in growth and feed use-efficiency. The immunomodulation and anti-inflammatory effects of dexamethasone could be part of a homeorhetic change that results in a shift from maintenance functions to support growth on calves exposed to heat stress.

Relationship between biomarkers and platelet aggregation activity in presence of hydrogen sulfide in patients with coronary heart disease

Biological significance of hydrogen sulfide (H2S) in regulation of platelet functions and in development of thrombosis is being studied, but there is no consensus on the role of H2S in these physiological processes. The platelets are very sensitive to various mediators released from blood vessels and blood cells. Multiple pro-inflammatory molecules may exert direct effects on the state of cardiovascular system. Thus, an imbalance in the production of pro-inflammatory and anti-inflammatory cytokines increases the risk of thrombosis, and it can lead to endothelial dysfunction, instability and rupture of atherosclerotic plaques. The aim of our study was to determine concentrations and identify the relationships between certain biomarkers (LIGHT, PlGF, IFNá2, TNFáâ, IL-3, IL-5, IL-6, IL-8, IL-15, IL-17F, MIP-1á, CXCL16) and collagen-induced platelet aggregation in presence of hydrogen sulfide exposure in patients with coronary heart disease. We performed a simple one-step comparative study which included 22 patients with coronary artery disease (CHD). The level of biomarkers was determined by multiplex analysis (xMAP technology). Platelet aggregation activity was studied by the turbidimetric assay. All samples were examined against the background of a 30-min pre-incubation with hydrogen sulfide, with the addition of an aggregation inducer (collagen, 2 mmol/L). Sodium hydrosulfide at a concentration of 10-6 M was used as a hydrogen sulfide donor. The results of comparative and correlation analysis were considered reliable at a statistical significance level of p 0.05. The patients were divided into two groups, i.e., group 1 (n = 10) showed a reduced aggregation or a decreased size of aggregates against the background of preincubation with H2S. In group 2 (n = 12), preincubation with H2S was followed by increased degree or size of platelet aggregates. The concentrations of tumor necrosis factor ligand (LIGHT), interferon IFNá2, interleukins IL-3, IL-8, IL-15, IL-17F, chemokine CCL3/MIP-1a were significantly increased in group 2 patients, where collagen-induced platelet aggregation increased upon preincubation H2S, as compared with patients in group 1. The correlation analysis revealed positive correlations found that in the 1st group of patients between the concentrations of MIP-1a (Rs = 0.56, p = 0.03; Rs = 0.69, p = 0.01), IL-5 (Rs = 0.83, p = 0.01; Rs = 0.73, p = 0.01), and IL-8 (Rs = 0.60, p = 0.02; Rs = 0.95, p = 0.01), respectively, and with both size of aggregates and the index of the platelet aggregation degree. Moreover, distinct correlations between the aggregate size and the concentration of IL-6 (Rs = 0.53, p = 0.04) were revealed. In the 2nd group of patients, correlations were found with the size of aggregates and PIGF (Rs = 0.59, p = 0.04), and between CXCL16 values and the size of aggregates (Rs = 0.58, p = 0.04), like as with the degree of aggregation (Rs = 0.65, p = 0.04). Thus, we have found that, in 2 groups of patients with coronary heart disease with increased collagen-induced platelet aggregation, preincubated with H2S, higher concentrations of inflammatory biomarkers (IFNá2, IL-3, IL-8, IL-15, IL-17F, MIP-1á) were detected. One may suggest that the more pronounced proinflammatory state in this group of patients may cause platelet resistance to inhibitory effect of hydrogen sulfide. In the 1st group of patients, we revealed multiple correlations of aggregation parameters with values of inflammatory markers (IL-5, IL-6, IL-8, MIP- 1a), which may be a pre-requisite for different corrective therapies for the patients of these groups.

Mediators of monocyte chemotaxis and matrix remodeling are associated with mortality and pulmonary fibroproliferation in patients with severe COVID-19.

Acute respiratory distress syndrome (ARDS) has a fibroproliferative phase that may be followed by pulmonary fibrosis. Pulmonary fibrosis following COVID-19 pneumonia has been described at autopsy and following lung transplantation. We hypothesized that protein mediators of tissue remodeling and monocyte chemotaxis are elevated in the plasma and endotracheal aspirates of critically ill patients with COVID-19 who subsequently develop features of pulmonary fibroproliferation. We enrolled COVID-19 patients admitted to the ICU with hypoxemic respiratory failure. (n = 195). Plasma was collected within 24h of ICU admission and at 7d. In mechanically ventilated patients, endotracheal aspirates (ETA) were collected. Protein concentrations were measured by immunoassay. We tested for associations between protein concentrations and respiratory outcomes using logistic regression adjusting for age, sex, treatment with steroids, and APACHE III score. In a subset of patients who had CT scans during hospitalization (n = 75), we tested for associations between protein concentrations and radiographic features of fibroproliferation. Among the entire cohort, plasma IL-6, TNF-α, CCL2, and Amphiregulin levels were significantly associated with in-hospital mortality. In addition, higher plasma concentrations of CCL2, IL-6, TNF-α, Amphiregulin, and CXCL12 were associated with fewer ventilator-free days. We identified 20/75 patients (26%) with features of fibroproliferation. Within 24h of ICU admission, no measured plasma proteins were associated with a fibroproliferative response. However, when measured 96h-128h after admission, Amphiregulin was elevated in those that developed fibroproliferation. ETAs were not correlated with plasma measurements and did not show any association with mortality, ventilator-free days (VFDs), or fibroproliferative response. This cohort study identifies proteins of tissue remodeling and monocyte recruitment are associated with in-hospital mortality, fewer VFDs, and radiographic fibroproliferative response. Measuring changes in these proteins over time may allow for early identification of patients with severe COVID-19 at risk for fibroproliferation.