IL-10 Levels Research Articles

The Role of Panax Notoginseng Saponins on Neuronal Oxidative Stress and Autophagy Response in Craniocerebral Injury Model Rats

This study assessed how IL-6 affects the body’s autophagy status by regulating JAK-STAT3 and explored the mechanism by which IL-6 inhibits JAK-STAT3 signaling pathway-mediated autophagy, and how Panax notoginseng total saponins promote neuronal cell regeneration in rats. A model of neuronal oxidative stress in craniocerebral injury model rats was established, and IL-6 levels were detected by ELISA. Rat neuronal cells were isolated and cultured, while dual-luciferase gene reporter experiments analyzed the targeting relationship between IL-6 and JAK. qRT-PCR detected expression of neuronal autophagy-related genes (JAK, STAT3, ULK1, OsATG7, FAM176A, and Beclin 1). The level of IL-6 in the craniocerebral injury model was significantly higher than that in the control group. IL-6 binds to 3′-UTR of JAK, and transfection with IL-6 inhibitor increases the relative luciferase activity. pMIR-JAK-mut group has no significant effect. There is a targeted regulatory relationship between IL-6 and JAK. Adding total saponins of Panax notoginseng combined with nursing intervention can promote reduction genetic expression related to neuronal autophagy damage. IL-6 can target and regulate JAK gene. IL-6 can promote neuronal development by regulating JAK-STAT3. Autophagy repairs damage and inhibits the autophagy state of cells. Panax notoginseng total saponins are effective medicinal components extracted from high quality panax notoginseng according to extraction and separation technology. The results from this study provide a better understanding of pathogenesis of neuronal oxidative stress in craniocerebral injury model rats and find potential intervention targets, which will provide more treatment methods for neuronal oxidative stress damage in craniocerebral injury model rats.

Amelioration of Neurochemical Alteration and Memory and Depressive Behavior in Sepsis by Allopurinol, a Tryptophan 2,3-Dioxygenase Inhibitor.

In response to inflammation and other stressors, tryptophan is catalyzed by Tryptophan 2,3-Dioxygenase (TDO), which leads to activation of the kynurenine pathway. Sepsis is a serious condition in which the body responds improperly to an infection, and the brain is the inflammation target in this condition. This study aimed to determine if the induction of TDO contributes to the permeability of the Blood-Brain Barrier (BBB), mortality, neuroinflammation, oxidative stress, and mitochondrial dysfunction, besides long-term behavioral alterations in a preclinical model of sepsis. Male Wistar rats with two months of age were submitted to the sepsis model using Cecal Ligation and Perforation (CLP). The rats received allopurinol (Allo, 20 mg/kg, gavage), a TDO inhibitor, or a vehicle once a day for seven days. Sepsis induction increased BBB permeability, IL-6 level, neutrophil infiltrate, nitric oxide formation, and oxidative stress, resulting in energy impairment in 24h after CLP and Allo administration restored these parameters. Regarding memory, Allo restored short-term memory impairment and decreased depressive behavior. However, no change in survival rate was verified. In summary, TDO inhibition effectively prevented depressive behavior and memory impairment 10 days after CLP by reducing acute BBB permeability, neuroinflammation, oxidative stress, and mitochondrial alteration.

Evaluation of the anti-arthritic properties of Litsea glutinosa (L.) C.B. Rob Bark: An integrated analysis utilizing in-silico, in-vitro, and in-vivo approaches, along with identification of major compounds

The current study explored the anti-arthritic properties of Litsea glutinosa bark extracts. The dried bark of L. glutinosa was defatted with n-hexane and extracted by methanol using a soxhlet apparatus. The bioactive compounds present in the extract were analysed by GC-MS and LC-MS. The methanol extract of L. glutinosa (MELG) was evaluated at different concentrations (25–400 mg/ml) for its in-vitro anti-arthritic efficacy using membrane stabilization and protein denaturation techniques. In in-vivo evaluation paw diameter, arthritic score, arthritic index, body weight, organ weight, and haematological and biochemical parameters were measured to assess anti-arthritic potential. Subsequently, pro-inflammatory and inflammatory cytokines such as tumour necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), IL-1β, cyclooxygenase-2 (COX-2), IL-13, and IL-10 were determined. The Compounds identified by GC–MS and LC-MS were subjected to an in-silico molecular docking analysis utilizing AutoDock 4.2 and BIOVIA-Discovery Studio Visualizer against COX-2, IL-1β, IL-6, and TNF-α. The in vitro anti-arthritic effect of MELG exhibited a dose-dependent reduction in membrane stabilization (67.9 % at 400 µg/ml) and protein denaturation assay (66.6 % at 400 µg/ml). MELG treated rats improved all arthritic parameters. Significant restoration of pro-inflammatory cytokines was observed in rats administered with MELG (200 & 400 mg/kg). In the MELG (400 mg/kg) treated group, there was a significant reduction in IL-10 (P˂0.001) and IL-13 (P˂0.05) levels and a substantial rise in IL-6 (P˂0.01), TNF-α (P̂˂0.001), and IL-1β (P˂0.01) levels. The presence of phytoconstituents was analyzed by GC–MS (Fourteen compounds) and LC-MS (Ten compounds). Boldine identified by LC-MS analysis, exhibited good docking scores against COX-2 (-8.7), IL-1β (-6.3 kcal/mol), IL-6 (-6.2 kcal/mol), and TNF-α (-6.7 kcal/mol).The presence of bioactive compound, boldine in MELG might be responsible for its anti-arthritic activity.

The influence of light on Interleukin-10: A preliminary study

Light influences circadian rhythms, including that of the stress hormone cortisol. Cortisol, in turn, has been observed to promote expression of the anti-inflammatory cytokine IL-10. It is thus of interest whether the cytokine IL-10 is also influenced by light, perhaps in accord with the diurnal variations in cortisol. Hence, this highly standardized preliminary sleep laboratory study in healthy adult men investigated a potential influence of different light exposure on IL-10 and cortisol concentrations in blood. In a between-subject design, N = 42 participants were exposed to either bright, dim, blue or red light after wake-up. Two mixed-model analyses with the factors of light condition and time (across eight IL-10 and cortisol sampling points) were conducted. Additionally, area under the curve measurements (AUCg and AUCi) were calculated for both cortisol and IL-10. Across all conditions, IL-10 and cortisol concentrations significantly changed over time. However, none of the light conditions exerted a greater influence on IL-10 or cortisol levels than others. For cortisol, there was greater total output (AUCg) in the blue-light condition in particular. Further research is needed to gain insight into whether or not types of light or cortisol levels have a hand in influencing natural IL-10 concentrations.

Preparation and structural characterization of selenium nanoparticles from Lactobacillus reuteri and their protective effects on DSS-induced ulcerative colitis in mice

In this study, selenium nanoparticles (SeNPs) with protection against dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice were prepared extracellularly by co-culturing a sodium selenite solution with Lactobacillus reuteri. Mutiple analytical techniques have shown that SeNPs are mainly composed of C, N, O, and Se elements and are spherical structures encapsulated by polysaccharides or proteins, with a diameter distribution of 70∼130 nm and a potential of approximately -25 mV. The results of cell experiments showed that the prepared SeNPs could significantly reduce the production of nitric oxide (NO) induced by lipopolysaccharide (LPS) in Raw264.7 cells and exert an anti-inflammatory effect by decreasing the levels of TNF-α and IL-1β and increasing the level of IL-10. Animal experiments demonstrated that the SeNPs could effectively alleviate symptoms, such as diarrhea, weight loss, bloody stool, colon shortening, and histopathological changes induced by DSS in mice. They could also reduce mucus damage, goblet cell depletion, and intestinal permeability. In addition, the prepared SeNPs could alleviate colitis by promoting the expression of tight junction proteins, occludin-1 and zonula occluden 1 (ZO-1) and inhibiting oxidative enzymes and pro-inflammatory factors, thereby protecting the barrier function. Analysis of intestinal microbiota revealed that the SeNPs could greatly modulate the gut microbiota in colitis, restore the normal levels of gut microbiota, and enhance immune regulation in mice, thereby inhibiting the further occurrence and development of UC.

Rebaudioside B Attenuates Lung Ischemia-reperfusion Injury Associated Apoptosis and Inflammation.

At present, no proven effective treatment is available for Lung Ischemiareperfusion Injury (LIRI). Natural compounds offer promising prospects for developing new drugs to address various diseases. This study sought to explore the potential of Rebaudioside B (Reb B) as a treatment compound for LIRI, both in vivo and in vitro. This study involved utilizing the human pulmonary alveolar cell line A549, consisting of epithelial type II cells, subjected to Oxygen-glucose Deprivation/recovery (OGD/R) for highthroughput in vitro cell viability screening. The aim was to identify the most promising candidate compounds. Additionally, an in vivo rat model of lung ischemia-reperfusion was employed to evaluate the potential protective effects of Reb B. Through high-throughput screening, Reb B emerged as the most promising natural compound among those tested. In the A549 OGD/R models, Reb B exhibited a capacity to enhance cell viability by mitigating apoptosis. In the in vivo LIRI model, pre-treatment with Reb B notably decreased apoptotic cells, perivascular edema, and neutrophil infiltration within lung tissues. Furthermore, Reb B demonstrated its ability to attenuate lung inflammation associated with LIRI primarily by elevating IL-10 levels while reducing levels of IL-6, IL-8, and TNF-α. The comprehensive outcomes strongly suggest Reb B's potential as a protective agent against LIRI. This effect is attributed to its inhibition of the mitochondrial apoptotic pathway and its ability to mitigate the inflammatory response.

Effects of dietary Brassica rapa L. polysaccharide on growth performance, immune and antioxidant functions and intestinal flora of yellow-feathered quail.

This study aimed to explore the impact of Brassica rapa L. polysaccharides (BRP) on the growth, immune response, antioxidant capacity, and cecal microbiota in yellow-feathered quails. A total of 250 one-day-old yellow-feathered quails, evenly divided by sex, were randomly assigned to five groups, with each group comprising ten replicates of five quails each. The control group (CON) received a basic diet, while the antibiotic control group (CTC) was fed a basic diet supplemented with chlortetracycline (0.05g/kg). BRP was administered at concentrations of 0.25g/kg (Low dose BRP, LBRP), 0.5g/kg (Medium dose BRP, MBRP), and 1g/kg (High dose BRP, HBRP). The duration of the experiment was 42 days. The results indicated that, compared to the CON group, the final body weight of quails in the MBRP group significantly increased (P < 0.05), and there was a significant difference in body weight between the LBRP group and the CTC group (P < 0.05). At 21 days of age, the average weights of the thymus and bursa of Fabricius in the MBRP group were significantly greater than those in the CON group (P < 0.05), with no significant difference observed when compared to the CTC group (P > 0.05); at 42 days of age, the average weight of the thymus in the MBRP group was significantly greater than that in the CON group (P < 0.05), with no significant difference observed compared to the CTC group (P > 0.05). At 21 days of age, the levels of IgA and IgG in the MBRP group were significantly elevated compared to the CON group (P < 0.05), with no significant difference noted compared to the CTC group (P > 0.05). Additionally, the MBRP group showed significant increases in CAT, T-SOD, and GSH-Px levels (P < 0.05) compared to the CON group; the levels of IL-1β and TNF-α were significantly reduced (P < 0.05), and the level of IL-10 was significantly elevated (P < 0.05) compared to the CON group. Furthermore, 16S rRNA sequencing revealed that BRP supplementation increased the populations of beneficial cecal bacteria such as Lactococcus, Weissella, Parabacteroides, and norank_f_Ruminococcaceae, and decreased the population of the harmful bacterium Campylobacter, indicating that BRP modulates the microbial community structure in the cecum of yellow-feathered quails. In summary, BRP enhanced the growth performance, serum immunoglobulin levels, antioxidant functions, and improved the intestinal microbiota in yellow-feathered quails.

Antibody isotyping and cytokine profiling in natural cases of Burkholderia mallei infection (glanders) in equines.

Immunological aspects of B. mallei infection were rarely studied in natural cases of equines. The present study was conducted to determine IgG, IgM, IgA and IgG (T) titre against recombinant Hcp1, TssA and TssB proteins and PilA-Hcp1-TssN-BipD and BpaB-BpaC- BMAA0553 chimeras and cytokine responses in glanders affected equine serum. The study was conducted on serum samples collected from 151 glanders positive equines which include horses (n=134), mules (n=16), and donkeys (n=01). The IgM, IgG, IgA and IgG (T) titre were determined against recombinant antigens by indirect ELISA and interleukin(IL)-1β, IL-17, IL-6, tumor necrosis factor alpha(TNF-α), monocyte chemoattractant protein 1 (MCP-1) and interferon gamma (IFN-γ) responses were measured by commercial ELISA kits. The study showed that glanders affected equines elicited strong antibody response against Hcp1, moderate responses against TssA and TssB, and weak responses against two chimeras. Among the cytokines, IL-1β, MCP-1, IL-17 and IL-6 concentration were significantly higher in glanders affected equine serum. We found that IgG antibody titre was higher than IgM, IgG (T) and IgA isotypes and Hcp1 was most predominant antibody inducers in comparison to TssA, TssB, PilA-Hcp1-TssN-BipD and BpaB-BpaC-T2SS proteins. The elevated level of IL-1β, MCP-1, IL-17, IL-6, IFN-γ and TNF-α observed in this study support the important role of this cytokines for augmenting cellular defence by recruitment of macrophages, neutrophil and dendritic cells against B. mallei infection. Further studies should be conducted to determine memory cell responses in natural cases of equine glanders using recombinant B. mallei proteins for identifying well-characterized immuno-protective vaccine candidates.

Peripheral immune signatures associated with the risk of hepatocarcinogenesis in cirrhotic Egyptian HCV patients before and after treatment with direct-acting antivirals.

Although direct-acting antivirals (DAAs) have revolutionized the management of chronic HCV, the debatable association with hepatocellular carcinoma (HCC) occurrence/recurrence has raised major concerns about their long-term use, especially in cirrhotic cases. The role of epithelial tight junction proteins (TJPs) in hepatocarcinogenesis has been highlighted; however, the association of their expression in peripheral blood mononuclear cells (PBMCs) with HCC has rarely been reported. This study aimed to explore the role of peripheral claudin (Cldn)1 in liver pathogenesis and its crosstalk with soluble immune mediators in HCC prognosis. The study population included six independent subgroups: healthy controls, cirrhotic/non-cirrhotic treatment-naïve HCV patients, DAA-SVR patients, and anticancer treatment-naïve de novo HCC patients. The laboratory tests included serum levels of alpha-fetoprotein (AFP), albumin, liver transaminases, total bilirubin, and CBC profiling. The serum levels of soluble cluster of differentiation (sCD)163, IL-10, and IL-12 were estimated by corresponding ELISA kits, whereas the levels of Cldn1 and transforming growth factor (TGF)-β in PBMCs were quantified using quantitative PCR (qPCR). Serum sCD163, IL-10, and IL-12 levels were significantly higher in the HCC patient group than in the control and non-malignant patient groups (P < 0.0001). No significant difference was detected in the serum levels of the three markers between cirrhotic and non-cirrhotic patients, whereas their levels were significantly different between cirrhotic and non-cirrhotic patients (P < 0.0001). Similarly, the transcriptional levels of peripheral Cldn1 and TGF-β were significantly higher in patients with HCC and non-malignant cirrhosis than in patients without cirrhosis (P = 0.0185-<0.0001 and 0.0089-<0.0001, respectively). Logistic regression analysis revealed a significant association between all the abovementioned markers and HCC (P = 0.0303 to < 0.0001), which was further confirmed by the results of receiver operating characteristic (ROC) analysis, which revealed an area under the curve (AUC) value ranging from 0.883 to 0.996. The calculated cutoff values demonstrated remarkable prognostic capacity, with ranges of 88-99.41% and 82.14-97.92% and positive/negative predictive values ranging from 84.62 to 98.3% and 92-98%, respectively. The proposed HCC predictors are novel non-invasive HCC biomarkers that maintain their predictive power under different pathological conditions and circumvent the drawbacks of conventional prognostic markers in patients with mild cirrhosis and/or normal AFP, albumin, and/or platelet counts.

Deranged cytokine levels are linked to cancer-related cognitive impairment in lymphoma patients receiving R-CHOP chemotherapy

Cancer-related cognitive impairment (CRCI) is a significant issue commonly observed following chemotherapy treatment. The study aimed to investigate the changes in cognitive function and their association with IL-6, IL-1β, and IL-10 levels before and after R-CHOP chemotherapy over six cycles. Seventy chemotherapy naïve, newly diagnosed lymphoma patients were enrolled. Cognitive functions and inflammatory cytokines were assessed at baseline (TP1), after 3rd cycle (TP2), and after 6th cycle (TP3). Patients, with mean age of 44.17 ± 13.67 years, showed significantly increased levels of IL-6 and IL-1β and decreased IL-10 levels over time (p < .001). On the Montreal Cognitive Assessment (MoCA), scores of domains such as executive functioning (p = .002), attention (p < .001), language (p < .001), recall (p = .005), and orientation (p < .001) significantly decreased post six cycles of R-CHOP chemotherapy. Correlation analysis at TP2 indicated a positive association between elevated IL-6 levels with a decrease in MoCA scores indicating a decline in cognitive function (ρ = 0.68, p < .001). At TP3, no association of MoCA scores with IL-6 and IL-1β was observed. Decreased IL-10 levels showed a weak association with decreased MoCA scores at TP2 and TP3 ( ρ = 0.2, p = .09; for TP3, ρ = 0.16, p = .17), but this was not significant. In summary, the findings of the present study highlight significant cognitive decline and changes in inflammatory cytokine levels following six cycles of R-CHOP. Objective cognitive assessments may be done to detect CRCI in patients treated with R-CHOP.

Design and synthesis of new nicotinamides as immunomodulatory VEGFR-2 inhibitors and apoptosis inducers.

Background: Nicotinamide-based VEGFR-2 inhibitors have good contribution in drug discovery.Aim: Development of novel nicotinamides as VEGFR-2 inhibitors.Methods: different in vitro and in silico assays were conducted to evaluate the VEGFR-2 inhibition and cytotoxicity.Results: Compound 16c displayed strongest anti-VEGFR-2 potentiality and good anti-proliferative effects. Compound 16c enhanced apoptosis and caused cell cycle arrest in the Pre-G1 and S phases. Compound 16c boosted the level of the apoptotic caspase-3 and inhibited the level of TNF-α and IL-6 in tumor cells. Molecular docking and molecular dynamics (MD) simulations indicated the outstanding binding potential of compound 16c against VEGFR-2.Conclusion: Compound 16c is a good candidate for the creation of a novel antiangiogenic lead anticancer medication.

Cytokine profile, differential somatic cell count, and oxidative status of Italian Mediterranean buffalo milk affected by the temperature–humidity index

In the context of climate change, there has been an increased interest in improving management practices for animals genetically adapted to extreme environmental conditions, such as buffaloes. The temperature–humidity index (THI) is used to determine the severity of heat stress in livestock. This study aimed to evaluate the cytokine profile, oxidative staus, differential somatic cell count (DCC), and the surface expression and activity of myeloperoxidase (MPO) in the somatic cells (SCs) of buffalo. Milk samples (n = 216) were collected from the spring to summer season under three different THI classes (THI &amp;lt; 72; ≤72 THI &amp;lt; 76, and THI ≥ 76). The cytokine profile was determined using ELISA, and the expression of DSCC and MPO was determined by flow cytometry. MPO activity was performed on SC extracts using a specific ELISA kit. Oxidative status was determined by the antioxidant/oxidant balance combining the free radical scavenging activity levels, and reactive oxygen and nitrogenous species. The results on the cytokine profile showed that at the THI ≥ 76 the levels of both IL-10 and IFN-γ were highest. IL-1β secretion was lower at the THI &amp;lt; 72 than at the THI values ranging from ≤72 THI &amp;lt; 76. Higher levels of both TNF-α and IL-12 were registered in both THI &amp;lt; 72 and THI ≥ 76 classes. The level of IL-4 was higher in the THI ≥ 76 class than in the ≤72 to &amp;lt;76 range. Data on DCC showed a decrease in the percentage of macrophages and lymphocytes as the THI increased from the ≤72 to &amp;lt;76 range to THI ≥ 76. Furthermore, the highest percentage of polymorphonuclear leukocyte (PMNLs) was registered in both ≤72 to &amp;lt;76 and THI ≥ 76 classes. The MPO activity and surface expression on SC were lower at a THI above 76, which could be associated with an absence of inflammation. A condition of oxidative imbalance was registered as demonstrated by the lower levels of antioxidant/oxidant balance along with increasing THI. Present data demonstrated that buffaloes were able to modulate the alteration of immune response activated by heat stress throughout a series of cross-linked mechanisms involving cytokine networks, different somatic cell distribution, and oxidative status.

Oxidative stress and mitochondrial dysfunction contributes to postoperative cognitive dysfunction in elderly rats dependent on NLRP3 activation.

Postoperative cognitive dysfunction (POCD), a complication following procedures such as orthopedic surgery, is associated with a worsened prognosis, especially in the elderly population. Several mechanisms have been proposedfor communication between the immune system and the brain after surgery. In an experimental tibial fracture (TF) model, we aimed to understand the role of the NLR family pyrin domain containing 3 (NLRP3) on oxidative stress and mitochondrial dysfunction as mechanisms underlying POCD in aged and adult rats.Adult or aged male Wistar rats were subjected to the TF model and receivedintracerebroventricularsaline or MCC950 (140ng/kg), a specific small-molecule inhibitor that selectively blocks activation of the NLRP3 inflammasome.We followed the control (sham) and TF groups treated with MCC950 or saline for seven days to determine cognitive function and survival.The prefrontal cortex and hippocampus were isolated for NLRP3 evaluation, cytokine analysis, oxidative stress measurements, myeloperoxidase activity, nitric oxide formation, mitochondrial respiratory chain enzymes, and succinate dehydrogenase (SDH) activity. Seven days after TF induction, NLRP3 levels increased in the hippocampus and prefrontal cortex in both ages, showed an enhancement in aged rats compared to adults, and experienced a reversal with MCC950 administration.The administration of MCC950 restored memory, IL-1β and IL-10 levels, nitrite/nitrate, lipid peroxidation in the hippocampus and prefrontal cortex, and preserved catalase activity in the prefrontal cortex in aged rats. At the same age, the complex I activity alteration in both regions and complex II, IV, and SDH in the prefrontal cortex werereversed. In conclusion, NLRP3 activation contributes to POCD development because it is intrinsically involved in mitochondrial dysfunction and oxidative stress after orthopedic surgery in aged rats.

Hemadsorption with CytoSorb in Infants with Sepsis: Non-Systematic Review of Cases

Sepsis is a severe and potentially life-threatening condition that occurs when the body’s response to an infection damages its own tissues and organs. It can lead to organ failure and death if not treated. Cytosorb is a promising medical device for hemadsorption in pediatric septic patients (under 18 years old). As many studies conclude, Cytosorb results in efficient hemodynamics stabilization. This paper is a nonsystematic review of cases. PubMed-, Google Scholar-, and Scopus-indexed journals were used to collect papers for the research. Overall, 11 pediatric cases (six journal articles) were collected. Reductions in interleukin (IL)-6 and IL-10 levels after hemoperfusion with CytoSorb suggest a potential benefit in modulating the inflammatory response in pediatric patients. Moreover, other septic shock indicators such as C-reactive protein, lactate, procalcitonin, ALT, and AST were also significantly reduced in surviving patients within the first few hours of hemadsorption with CytoSorb. The use of CytoSorb seems to be efficient in managing different sepsis-related conditions, even in neonatal and infant populations, as a valuable supplementary tool. However, overcoming the obstacles associated with the age and weight of pediatric patients might necessitate the creation of CytoSorb devices tailored specifically to their needs.

Pathophysiology of De Novo Food Allergies After Solid Organ Transplant in Pediatric Patients.

De novo food allergy is a common phenomenon among pediatric solid organ recipients (8.5%-57%) when compared with the general population (0.45%-10%). Other associated disorders include non-IgE-mediated immune reactions and clinical predisposition to asthma and alterations in the oral mucosa. Originally, passive mechanisms (passive transfer of IgE and immune cells) were thought to be responsible for acute, transient cases of food allergies with a previous history of sensitization for a specific allergen in the donor. Recently proposed pathophysiological mechanisms to explain de novo allergies include TH2/B-cell imbalance, regulatory T-cell (Treg) disruption, gastrointestinal immaturity, and altered gastrointestinal permeability. Recent studies also suggest that immunosuppressive drugs, especially tacrolimus, promote naïve T-cell differentiation into TH2 cells, IgE-promoting cytokine production, decreased IL-5 and IL-10 levels, increased IgA levels, and Treg disruption. Such immunological interactions, in conjunction with altered intestinal permeability, intestinal immaturity in children, history of viral infection, and a personal history of allergies or eczema, are thought to explain most clinical cases of pediatric de novo food allergy after solid organ transplantation reported in the literature. A better understanding of the immunological mechanisms underpinning organ donors and recipients may unveil some of the caveats concerning therapeutic management and improve the quality of life of affected individuals.

Effects of CFTR-ENaC on spinal cord edema after spinal cord injury

Abstract Objective To explore the role of cystic fibrosis transmembrane conduction regulator (CFTR)-Epithelial sodium channel (ENaC) in spinal cord edema after spinal cord injury (SCI) and the related mechanism. Methods Lipopolysaccharide (LPS)-treated M1830 astrocytes were applied as the SCI in vitro model. Immunohistochemistry, real-time PCR, and Western blotting were utilized to detect CFTR and ENaC expression. Enzyme-linked immunosorbent assay was used to measure inflammatory cytokines including TNF-α, IL-1β, IL-6, and IL-18. Transmission electron microscope examined ultrastructure changes, while CFTR-172 or Capsazepine treatment assessed their effects on edema and inflammation. Western blot analysis was employed to evaluate the PI3K, p-PI3K, AKT, and p-AKT signaling pathways in treated cells. Results LPS-treated M1830 cells exhibited increased levels of CFTR and pro-inflammatory cytokines, including TNF-α, IL-1β, IL-6, and IL-18, alongside decreased ENaC expression and suppressed p-PI3K/PI3K and p-AKT/AKT levels. Degeneration of the myelin sheath and axons was observed in LPS-treated M1830, while changes in ultrastructural were recovered after adding CFTR-172 or Capsazepine. The level of CFTR, TNF-α, IL-1β, IL-6, and IL-18 was decreased, while the level of ENaC, p-PI3K/PI3K, and p-AKT/AKT was increased obviously in LPS-treated M1830 with CFTR-172, Capsazepine, or IGF-1. Conclusion Down-regulation of CFTR and up-regulation of ENaC can attenuate inflammation in SCI by activating the PI3K/AKT signaling pathway, highlighting a new therapeutic approach for SCI treatment. These findings address a critical gap in current SCI treatments and suggest a novel intervention strategy targeting ion channel regulation.

DEPTOR attenuates asthma progression by suppressing endoplasmic reticulum stress through SOD1.

Endoplasmic reticulum (ER) stress has been shown to play a pivotal role in the pathogenesis of asthma. DEPTOR (DEP Domain Containing MTOR Interacting Protein) is an endogenous mTOR inhibitor that participates in various physiological processes such as cell growth, apoptosis, autophagy, and ER homeostasis. However, the role of DEPTOR in the pathogenesis of asthma is still unknown. In this study, an ovalbumin (OVA)-induced mice model and IL-13 induced 16HBE cells were used to evaluate the effect of DEPTOR on asthma. A decreased DEPTOR expression was shown in the lung tissues of OVA-mice and IL-13 induced 16HBE cells. Upregulation of DEPTOR attenuated airway goblet cell hyperplasia, inhibited mucus hypersecretion, decreased the expression of mucin MUC5AC, and suppressed the level of inflammatory factors IL-4 and IL-5, which were all induced by OVA treatment. The increased protein expression of ER stress markers GRP78, CHOP, unfolded protein response (UPR) related proteins, and apoptosis markers in OVA mice were also inhibited by DEPTOR overexpression. In IL-13 induced 16HBE cells, overexpression of DEPTOR decreased IL-4, IL-5, and MUC5AC levels, preventing ER stress response and UPR process. Furthermore, from the proteomics results, we identified that SOD1 (Cu/Zn Superoxide Dismutase 1) may be the downstream factor of DEPTOR. Similar to DEPTOR, upregulation of SOD1 alleviated asthma progression. Rescue experiments showed that SOD1 inhibition abrogates the remission effect of DEPTOR on ER stress in vitro. In conclusion, these data suggested that DEPTOR attenuates asthma progression by suppressing endoplasmic reticulum stress through SOD1.

Amelioration of propionic acid-induced autism-like behaviors in rats by fenofibrate: A focus on reduction of brain galectin-3 levels.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interactions and repetitive behaviors. This study examines the effects of fenofibrate on a propionic acid (PPA)-induced rat model of ASD, focusing on behavioral changes, inflammatory markers, and histological findings. Thirty male Wistar rats were divided into three groups: a control group, a group receiving PPA and saline, and a group treated with PPA and fenofibrate for 15 days. Behavioral assessments, including the three-chamber sociability test, open-field test, and passive avoidance learning, were conducted. Biochemical analyses measured TNF-α, NGF, IL-17, IL-2, and galectin-3 levels in brain tissues. Histological evaluations focused on Purkinje neuron counts in the cerebellum and neuronal changes in the CA1 and CA3 regions of the hippocampus, along with glial fibrillary acidic protein (GFAP) levels. Fenofibrate treatment significantly improved behavioral outcomes, reducing autism-like behaviors compared to the PPA/saline group. Biochemically, the PPA/saline group showed elevated levels of malondialdehyde, TNF-α, IL-2, IL-17, and galectin-3, which were reduced following fenofibrate treatment. Histologically, the PPA/saline group exhibited fewer, dysmorphic Purkinje neurons and increased glial activity in the CA1 region, both of which were ameliorated by fenofibrate treatment. Fenofibrate shows promise in mitigating autism-like behaviors in a rat model of ASD, likely due to its antioxidative and neuroprotective properties, which contribute to preserving neuronal integrity and reducing inflammation.

Abstract 4136532: The Agonism of Macrophage Migration Inhibitory Factor Modulates Neutrophils Subsets and Rescues an Impaired Tolerance to Ischemic Insults in Aging

Introduction: An impaired cardiac macrophage migration inhibitory factor (MIF) signaling in aging during ischemia and reperfusion (I/R) can be rescued by a MIF agonist, MIF20. Alterations in cardiac metabolic homeostasis cause inflammation under I/R. Thus, MIF agonism with MIF20 could modulate cardiac inflammatory response during I/R. Hypothesis: MIF20 modulates the polarization of neutrophil subset and rescues the impaired immune response under I/R in aging. Methods: Young (3-months)/aged (24 months) C57BL/6 wild type (WT) mice and MIF flox/flox (3 months)/cMIF -/- (cardiomyocyte MIF deletion, 3 months) were subjected to LAD ligation of for 45 min of ischemia, followed by 24 hr of reperfusion. MIF20 (0.15 µg/kg, i.v.) was injected at 5 minutes before reperfusion. The immune cells were determined with flow cytometry. mRNA and protein were measured by real-time qPCR, immunoblotting/cytokine array. Results: Administration of MIF20 reduced myocardial infarct by I/R in young/aged WT and MIF flox/flox but not in cMIF -/- mice. The flow cytometry showed that I/R stress dramatically triggered neutrophils infiltration, which occurred in both left ventricle and right ventricle. Intriguingly, MIF20 treatment reduced the I/R-induced neutrophil recruitment in hearts. Aged versus young WT myocardium recruited more N1 neutrophils (CD206 - ), while MIF20 treatment rescued the impaired N1 neutrophils response in aging. Moreover, MIF20 can increase infiltration of N2 neutrophils (CD206 + ) in both young and aged WT hearts. The recombinant MIF can directly trigger N2 neutrophil polarization and N1 neutrophil reduction in cMIF -/- hearts, indicating the critical role of MIF/CD74 axis in neutrophil polarization by I/R challenge. The cytokine array showed that MIF20 treatment can trigger cardiac TGF-β levels and upregulate IL-10 levels in serum under I/R, since TGF-β and IL-10 are critical factors involved in the N2 neutrophils’ polarization. Interestingly, MIF20 increased SiglecF marker on neutrophils in the aged versus young hearts, suggesting that MIF20 rescue the long-lived neutrophil population (SiglecF high ) which could enhance phagocytosis to repair damaged myocardium during I/R conditions. Conclusions: An impairment of metabolic homeostasis and inflammatory response occurred in cardiac aging. MIF agonism with small molecule MIF20 can rescue the capacity of MIF/CD74 signaling to maintain metabolic homeostasis and inflammatory response in aging under I/R pathological conditions.

Comparison of inflammatory mediator cytokine responses to inactivated virus platform COVID-19 vaccines between elderly and young adult populations

The coronavirus disease 2019 (COVID-19) pandemic has encouraged global vaccine research, yet vaccine effectiveness in the elderly remains a concern due to immunosenescence. The aim of this study was to compare the cytokine response elicited by an inactivated virus-based COVID-19 vaccine between elderly and young adults, focusing on key cytokines involved in cellular and humoral immunity: tumor necrosis factor-alpha (TNF-α), interleukin (IL)-2, IL-6, IL-10, and interferon-gamma (IFN-γ). A cross-sectional study was conducted in the Jakarta-Bogor region of Indonesia from January 2023 to December 2023. The study population was divided into two age cohorts: elderly (60−85 years) and younger adults (30−40 years). Blood samples were collected twice, after the first booster dose and four weeks after the second booster dose. Serum cytokine concentrations were measured using Luminex assays with microparticles conjugated to monoclonal antibodies against TNF-α, IL-2, IL-6, IL-10, and IFN-γ. Comparisons of the cytokine levels were conducted using Student’s t-tests or Mann-Whitney U tests as appropriate. A total of 74 individuals were included, with 37 each in the elderly and young adult groups. The results showed significant differences in cytokine responses between the two age groups. After the first booster, the levels of IL-6 and IFN-γ were significantly higher in young adults compared to the elderly. After the second booster, the levels of IL-6 were still significantly higher in the young adult group compared to the elderly group (p=0.001). Data indicated that after the second booster dose, the levels of TNF-α increased significantly in the young adult group only (p=0.004), while the levels of IL-2 (p=0.040) and IFN-γ (p=0.006) increased in the elderly group only compared to after the first dose. IL-10 levels increased in both groups (both had p=0.020). This study highlights that young adults had stronger pro-inflammatory responses, while the elderly relied more on IL-2 and IFN-γ for T-cell immunity, suggesting the need for vaccination strategies for the elderly to optimize immune responses.