Interleukin IL-6 Research Articles

Oxidative, epigenetic changes and fermentation processes in the intestine of rats fed high-fat diets supplemented with various chromium forms

The aim of the study was to determine how feeding rats a high-fat diet (F) supplemented with various forms of chromium affects the responses of the immune and redox systems, as well as epigenetic changes in the ileal tissue and the course of fermentation processes in the caecum. The rats received a pharmacologically relevant dose 0.3 mg Cr/kg body weight in form of chromium(III) picolinate (Cr-Pic), chromium (III)-methionine (Cr-Met), or chromium nanoparticles (Cr-NPs). The F increased DNA oxidation and raised the level of interleukin IL-6. The F was shown to reduce the intensity of fermentation processes in the caecum while increasing the activity of potentially harmful enzymes in the faeces. The addition of Cr in the form of Cr-NPs and Cr-Met in rats fed F beneficially increased mobilization of enzymes of the DNA repair pathway. All forms of Cr, but especially Cr-NPs, beneficially decreased the activity of caecal bacterial β-glucuronidase, faecal β-glucosidase and β-glucuronidase. However, due to the increase in level of cytokine IL-2 in small intestinal wall, induced by all tested forms of chromium, it is difficult to state conclusively that this element can mitigate unfavourable pro-inflammatory and oxidative changes induced by a F in the small intestinal wall.

Follicular Fluid Growth Factors and Interleukin Profiling as Potential Predictors of IVF Outcomes.

Growth hormone (GH) has gained attention as an anti-aging compound enhancing oocyte quality. In fact, GH is known to activate intrafollicular metabolic events for oocyte maturation. Insulin growth factor I (IGF1) is another ovarian growth factor that mediates the FSH and GH actions. Cytokines could also increase IVF outcomes. Indeed, IL-6 is a pleiotropic cytokine with multiple cellular effects that can vary based on the physiological environment. IL-6 may also play an important role in follicular development (Yang et al., J Assist Reprod Genet, 2020, 37 (5), 1171–1176). Clinical studies have been performed to explore the potential role of IL-6 in human oocyte maturation and subsequent embryonic development. To date, the answers are not conclusive. During peri-implantation, many cytokines balances are regulated like pro-inflammatory and anti-inflammatory interleukins. The pro-inflammatory properties of IL-17 and its impact on the tumor microenvironment or autoimmune diseases are characterized, but new dimensions of IL-17 activity that promotes embryo implantation are not well explored. In the search for answers, our study compared concentrations of growth factors IGF1, GH, and interleukins IL-6 and IL-17 in the follicular fluid (FF) from 140 women divided into two groups depending on bad (G1) or good prognosis (G2) and investigated the relationships between these FF components’ levels and the main parameters of IVF. GH, IGF1, and IL-6 were significantly higher for G2. For GH, it was negatively correlated to patient age and positively correlated to maturity rate and IGF1. Moreover, GH and IGF1 were correlated to the top embryo rate and cumulative pregnancy rate. Regarding IL-6, it was correlated to IGF1 level, endometrium thickness, and implantation rate. As for IL-17, it was only correlated to IL-6. Consequently, all these FF components were predictive of oocyte quality except IL-17. GH seemed to be the best biomarker of this quality.

Effects of different probiotic strains B. lactis, L. rhamnosus and L. reuteri on brain-intestinal axis immunomodulation in an endotoxin-induced inflammation.

The study evaluated the effects of supplementation with three different probiotic strains Bifidobacterium lactis (LACT GB™), Lactobacillus rhamnosus (RHAM GB™) and Lactobacillus reuteri (REUT GB™) on brain-intestinal immunomodulation in an animal model of LPS-induced inflammation. Fifty mice Balb/C were distributed into five groups: control; lipopolysaccharide (LPS); LPS + B. lactis (LACT GB™); LPS + L. rhamnosus (RHAM GB™); and LPS + L. reuteri (REUT GB™). The animals were supplemented with their respective probiotic microorganisms daily, for 30days, at a concentration of 1 × 109CFU/animal/day. After 30days of supplementation, animals received the inflammatory insult by LPS (15mg/kg). Behavioral tests, oxidative stress and inflammation were performed, as well as gut and brain histology. In the behavioral test, LPS + B. lactis group was less anxious than the other groups. Serum interleukin IL-1β and IL-6 levels increased in all groups that received the LPS insult, and there was a reduction in inflammation in the supplemented groups when compared to the LPS group in brain and gut. There is a reduction in myeloperoxidase activity and oxidative stress in groups supplemented with probiotics. Inintestine histological analysisoccurs damage tothe tissue integrity in the LPS group, in the other hand,occurs preservation of integrity in the probioticsupplemented animals. In the brain, infiltrates of perivascular inflammatory cells can be seen in the LPS group. The three probiotic studies showed efficient immunomodulating activity and ensured integrity of the intestinal barrier function, even after the severe insult by LPS. These results show the important role of probiotics in the gut-brain axis. Graphical abstract illustratively represents the gut-brain axis and how different probiotic strains influence the immunomodulatory response releasing different pro- and anti-inflammatory cytokines, and their role in the balance of dysbiosis.

Effects of Total Sulfur Amino Acids on Growth Performance, Immunity, and Meat Yield in Broilers Fed Diets With and Without Antibiotics.

Two experiments were conducted to evaluate the effects of digestible sulfur amino acids (SAA) on performance, carcass yield, immunity, and amino acid transporters in broilers fed diets with or without an antibiotic growth promoter (AGP). In experiment 1, a total of 250 1-day-old Cobb500 male chicks were assigned to battery cages with two levels of AGP (0 and 0.05% bacitracin) and five levels of SAA (0.7, 0.8, 0.9, 1.0, and 1.1%) for 21 d. In experiment 2, a total of 900 1-day-old Cobb500 male chicks were assigned to floor pens with two levels of AGP and three levels of SAA for the starter (0.7, 0.8, and 0.9%) or finisher phase (0.52, 0.62, and 0.72%) for 42 d. In experiment 1, from 0 to 7 d, the body weight gain (BWG) was the lowest for birds fed 0.7% SAA. The AGP significantly decreased the feed conversion ratio (FCR), and birds fed 0.9 and 1.1% SAA had significantly lower FCR than 0.7% SAA. From 8 to 14 d, for the AGP-fed birds, the lowest BWG was observed in the 0.7% SAA group. In birds not fed AGP, birds fed 0.8% SAA had higher BWG than 0.7 and 1.1% SAA. Birds fed 0.7% SAA diet had lower feed intake (FI) than 0.8% SAA and higher FCR than 0.8, 0.9, and 1.0% SAA. In experiment 2, from 0 to 21 d, the lowest BWG and the highest FCR were observed in birds fed 0.7% SAA, whereas birds fed 0.9% SAA had the highest BWG and lowest FCR. From 22 to 42 d, FCR was lower for birds fed AGP, and for birds fed 0.72%. Interactions between the factors were found for FI and BWG. The whole thigh and wing weights were the highest for 0.62% SAA, and the pectoralis major weight was higher for birds fed 0.62% SAA than those fed 0.52% SAA. There was an interaction between SAA and AGP for Lat1 (large neutral amino acid transporter) expression, and AGP-fed birds had higher expression of ileal interleukin 1β (Il−1β gene). The interleukin 10 (Il-10) expression was upregulated in the ileum. There was an interaction between factors for sodium-dependent neutral amino acid transporter B [0] AT1 (SLC6A19) expression. The results suggested that both AGP and SAA supplementation would affect the growth performance of the broilers.

Local and Systemic Effects of Green Coffee Extract (Coffea canephora) in Animal Model of Colorectal Carcinogenesis

ObjectivesEvaluate the local and systemic effects of aqueous extract of green coffee (GCE) in colorectal carcinogenesis (CRC) induced in rats. MethodsAdult Wistar rats (n = 48) were divided into two groups (C and T, n = 24). Group T was induced to CRC with 1,2-dimethylhydrazine (55 mg/kg, subcutaneously, weekly) for 5 weeks, and during this period all animals received standard AIN93-M diet. From week 6 to 15, the animals were divided into 4 groups (n = 12): C (healthy control fed AIN93-M diet), T (CRC- induced, fed AIN93-M diet), CGC (healthy control, fed AIN93-M diet + GCE), TGC (CRC-induced, fed AIN93-M diet + GCE). At 10th week, the pre-neoplastic lesions were evaluated in 4 rats from each group. The remaining rats (n = 8) were feed their experimental diet until the 15th week. In the last week, 24 h-urine collection was performed for intestinal permeability analysis using lactulose (100 mg/kg) and mannitol (50 mg/kg) administration. Afterwards, blood samples were collected to the analyses of plasma cytokines (TNF-alpha, interleukins IL-6, 10 and 12) and total antioxidant capacity (TAC). Large intestine content was collected for pH and secretory immunoglobulin A (sIgA) analyses. The microscopic lesions were evaluated in the colorectal mucosa. ResultsTGC group had the highest aberrant crypt foci (ACF) count, 51% higher compared to the T group. Intestinal permeability was increased in the T group. There was no significant difference in the quantification of cytokines TNF-alpha, IL-6, 10 and 12. Both TGC and T showed high values of TAC. Intestinal pH was significantly higher in CGC group compared to TGC. There was no significant difference in the quantification of sIgA between groups. The reduction of malignant neoplastic changes was 42% and of benign changes was 66% and there was a reduction of 33.33% and 20% of hyperplasia and dysplasia, respectively, in TGC compared with T group. ConclusionsGCE was beneficial for intestinal permeability and controlled the development of neoplasms in the colorectal mucosa, without interfering with systemic inflammation, reinforcing that GCE reduces the risk of developing the CRC. Funding SourcesThis study was financed by CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) and FAPES (Fundação de Amparo à Pesquisa e Inovação do Espírito Santo), Brazil.

Effects of acute heat stress on liver damage, apoptosis and inflammation of pikeperch (Sander lucioperca)

Pikeperch (Sander lucioperca) is a sub-cold water fish species with high aquaculture potential. Its culture is seriously affected by increasing summer temperatures in recent years. Aim to investigate the effects of heat stress on apoptosis, oxidative stress, and the immune response in pikeperch. the fish were heat stressed at 30 °C, 32 °C and 34 °C for 2h respectively, followed by a 48h recovery period. The results showed that as temperature increased, the contents of malondialdehyde (MDA) and hydrogen peroxide (H2O2) in the liver increased significantly. Meanwhile, acute heat stress results in progressive deleterious alterations in liver tissue, especially vascular rupture, blood infiltration, and severe vacuolation at 34 °C. TUNEL staining revealed that the apoptosis level increased significantly with the rising temperature. Acute heat stress significantly induced the mRNA expression of apoptosis-related genes, including tumor suppressor (p53), B-cell lymphoma-2 (bcl-2), bcl-2-associated X (bax), apoptotic protease activating factor-1 (apaf-1), cysteinyl aspartate specific proteinase (caspase-3 and caspase-9), and the expression of p53 was also positively correlated with bax expression and the bax/bcl-2 ratio. Additionally, caspase-3 and caspase-9 activity increased significantly at 34 °C compared with the control group (23 °C). Innate immune genes, including tumor necrosis factor (tnf-α), interleukins (il-7, il-8, il-10 and il-1β), complement 3 (c3) were activated under acute heat stress, and H2O2 content was positively correlated with the expressions of tnf-α and il-1β. After the temperature reached again 23 °C, most measured indexes in heat-stressed groups didn't return to stress-free levels, and liver tissue also didn't return to its normal state in the histopathology. It was found that p53-mediated mitochondrial apoptosis pathway was triggered in pikeperch under acute heat stress, and there may be a vicious cycle between oxidative stress and inflammation. In summary, the present study is helpful to elucidate how acute heat stress mediates liver injury of pikeperch through mitochondrial pathway, inflammation and oxidative stress.

The Effect of Hydroalcoholic Seed Extract of Securigera Securidaca on the Hepatic Renin-Angiotensin System in the Streptozotocin-Induced Diabetic Animal Model

Background: The aim of the study was to investigate the effect of hydroalcoholic seed extract of Securigera securidaca (S. securidaca) (HESS) on liver local reninangiotensin system (RAS) in streptozotocin-induced diabetic rats. Methods: Three groups of diabetic male Wistar rats were treated with different doses of HESS (100, 200, 400 mg/Kg-BW), and the results were compared with diabetic and healthy control groups. To test the effects of HESS on liver local RAS as well as its alternative pathway, the tissue levels of renin, angiotensin-converting enzyme (ACE), ACE2, angiotensin-II (Ang-II), and Ang-(1-7) were measured. The oxidative state of liver tissue was evaluated by biomarkers of malondialdehyde (MDA), total oxidant status (TOS), and total antioxidant status (TAS). Due to the association between local RAS activity and tissue inflammation, the production of interleukins (IL) IL-1, IL-6, tumor necrosis factor alfa (TNF-a), and IL-10 in the liver was assayed in the experimental group. Results: Dose-dependent effects of HESS showed that the highest dose of the extract had a reducing effect on the hepatic levels of local RAS components including angiotensinogen, ACE, and Ang-II. Surprisingly, despite the decrease in tissue level of ACE2, an increase in Ang-(1-7) tissue concentration was observed. Decreased local RAS activity through treatment with the highest dose of HESS was associated with decreased tissue levels of proinflammatory cytokines (IL-1, IL-6, TNF-a), and increased anti-inflammatory cytokine (IL-10). Most of the effects of the extract are attributed to its antioxidant properties. Conclusions: S. securidaca seed can be suggested as a suitable drug supplement to prevent hepatic complications of diabetes.

Extracellular Nucleophosmin Is Increased in Psoriasis and Correlates With the Determinants of Cardiovascular Diseases.

We previously showed that genotoxic stress induced an active extracellular release of nucleophosmin (NPM) in human cardiac mesenchymal progenitor cells, and that serum deprivation provokes NPM secretion from human endothelial cells, eliciting inflammation via nuclear factor kappa B (NF-kB) transcriptional activation. In this study, we wanted to determine whether NPM was similarly modulated in the skin and plasma of psoriatic patients (Pso). We found that NPM was induced in 6 skin biopsies compared to 6 normal skin biopsies and was markedly increased in lesional (LS) vs. non-lesional skin (NLS) biopsies. Moreover, NPM was also increased at the transcriptional levels in LS vs. NLS. Both the innate stimuli, such as lipopolysaccharides and Poly inositol–cytosine and adaptive stimuli, that is, cytokine mix, were able to induce the extracellular release of NPM in immortalized keratinocytes and human skin fibroblasts in the absence of cytotoxicity. Interestingly, NPM interacts with Toll-like receptor (TLR)4 in these cells and activates an NF-kB-dependent inflammatory pathway upregulating interleukin IL-6 and COX-2 gene expression. Finally, circulating NPM was increased in the plasma of 29 Pso compared to 29 healthy controls, and positively correlates with psoriasis area severity index (PASI) and with determinants of cardiovascular diseases (CVDs), such as pulse wave velocity, systolic pressure, and left ventricular mass. Furthermore, NPM positively correlates with miR-200c circulating levels, which we previously showed to increase in Pso and correlate with CVD progression. Our data show that circulating miR-200c is physically associated with extracellular NPM, which most probably is responsible for its extracellular release and protection upon cytokine mix via a TLR4-mechanism. In conclusion, NPM is increased in psoriasis both in the skin and plasma and might be considered a novel biologic target to counteract chronic inflammation associated with CVD risk.

A human coronavirus OC43-derived polypeptide causes neuropathic pain.

Human coronaviruses have been recently implicated in neurological sequelae by insufficiently understood mechanisms. We here identify an amino acid sequence within the HCoV‐OC43 p65‐like protein homologous to the evolutionarily conserved motif of myelin basic protein (MBP). Because MBP‐derived peptide exposure in the sciatic nerve produces pronociceptive activity in female rodents, we examined whether a synthetic peptide derived from the homologous region of HCoV‐OC43 (OC43p) acts by molecular mimicry to promote neuropathic pain. OC43p, but not scrambled peptides, induces mechanical hypersensitivity in rats following intrasciatic injections. Transcriptome analyses of the corresponding spinal cords reveal upregulation of genes and signaling pathways with known nociception‐, immune‐, and cellular energy‐related activities. Affinity capture shows the association of OC43p with an Na+/K+‐transporting ATPase, providing a potential direct target and mechanistic insight into virus‐induced effects on energy homeostasis and the sensory neuraxis. We propose that HCoV‐OC43 polypeptides released during infection dysregulate normal nervous system functions through molecular mimicry of MBP, leading to mechanical hypersensitivity. Our findings might provide a new paradigm for virus‐induced neuropathic pain.

Effects of dietary supplementation of trans-anethole on the intestinal antioxidant status, immune function, and liver lipid metabolism in broilers

This study was aimed to investigate the effects of trans-anethole (TA) on intestinal antioxidant status, immune function and liver lipid metabolism in broilers. A total of 256 1-day-old Arbour Acres broilers were allocated to 4 treatment groups with 8 birds per replicate. TA was added to diets at a concentration of 0 (control), 400, 600, and 800 mg/kg for 42 days. Dietary supplementation of TA increased the average daily feed intake (ADFI) of birds throughout the entire period. TA supplemented at 400 mg/kg of diet contributed to the lowest jejunal and ileal malondialdehyde (MDA) concentration on d 42, and the highest ileal total superoxide dismutase (T-SOD) activity on d 21 and d 42. TA supplementation at the concentration of 400 and 600 mg/kg of diet increased mRNA expression of ileal interleukin (IL)-4 on d 21, and intestinal secretory immunoglobulin A (sIgA) concentration on d 42. Supplementation of TA at the concentration up to 800 mg/kg of diet had adverse effects on intestinal antioxidant status, immune function and liver lipid metabolism compared with control group. Differently, TA supplemented at 400 mg/kg led to lower mRNA expression of liver ACC1, FASN, sterol regulatory element-binding protein 1c (SREBP-1), and higher CPT1 on d 42. In conclusion, TA inclusion improved intestinal antioxidant status and immune function, and enhanced liver lipid metabolism of broilers. HIGHLIGHTS Supplementation of 400 mg/kg of TA increased intestinal antioxidant status and immune function, and promoted liver lipid metabolism of broilers compared with non-supplemented group.

Cytokines in temporomandibular joint synovial fluid and tissue in relation to inflammation.

BackgroundSynovial tissue is known to be the origin of inflammation in joint disease. Despite this, synovial fluid is the main biological specimen of choice in temporomandibular joint (TMJ) inflammation and pathology biomarker research. No comparison of TMJ protein content between synovial fluid and synovial tissue has been made.ObjectivesThe aim of this study was to investigate whether cytokine concentrations in synovial fluid can be related to cytokine concentrations in synovial tissue and to analyse correlation of clinical parameters reflecting local inflammation to cytokine concentrations.MethodsSynovial tissue and fluid samples were obtained during the same surgical procedure from a cohort of 101 patients with TMJ disorders. Interleukin (IL) 1β, IL‐6, IL‐8, IL‐10 and tumour necrosis factor α (TNF‐α) were analysed in the samples and an intraindividual correlation made. Various patient‐specific factors related to TMJ inflammation were associated with the cytokine concentrations in synovial fluid and tissue.ResultsNo correlation between cytokine concentration in synovial fluid and synovial tissue was found, except for IL‐8 (ρ = .284, p = .024). Synovial tissue cytokines correlated strongly to inflammation‐related factors: diagnosis (IL‐1β, p = .001; TNF‐α, p = .000; IL‐10, p = .000), TMJ palpation pain (IL‐1β, p = .024; TNF‐α, p = .025), synovitis score (IL‐1β, p = .015) and subjective TMJ pain (TNF‐α, p = .016). Synovial fluid cytokines showed no significant relations to inflammation.ConclusionsThe investigated cytokine concentrations showed weak correlations between synovial fluid and synovial tissue, besides IL‐8. Synovial tissue appeared to reflect inflammation to a higher extent than synovial fluid. Thus, suggesting that synovial tissue research should complement synovial fluid in future explorations of TMJ pathology and inflammation.

Dexamethasone, Interleukin 6, and the Adrenal Gland are the Real Battles for COVID-19: Our Molecular Docking, Physiological, and Immunological Explanations of Why the Clinical Benefit of Dexamethasone is More Evident in Males

More than two years have passed since the pandemic and despite all the efforts of researchers, the pathogenesis of the SARS-CoV-2 has not yet been resolved. The SARS-CoV-2 coronavirus that causes COVID-19 has high ability of mutation resulting in different variants of the virus. This mutation helps the virus bypass the body's immune defenses such as innate and adaptive immunity. Interleukin (Il-6), neutrophils, high ferritin, and high D dimer are crucial markers for all sorts of cells on the lengthy path to treatment of COVID-19. IL-6 is one of the key mediators of inflammation and viral cytokine storm in COVID-19 patients. In humans, interleukin (IL)-6 is a strong stimulator of the hypothalamic-pituitary-adrenal (HPA) axis at all levels, and it appears to have a pathogenic role in chronic stress and physiological aging. The adrenal glands have earned further recognition as key modulators of immune function, because secretory products of the adrenal glands. Dexamethasone inhibits TNF-α–induced IL-6 mRNA expression and protein secretion by reducing IL-6 mRNA stability. Although Dexamethasone provides benefits in patients with coronavirus disease but there is sex linked difference between male and female at response to this drug. It was showed that this drug might indeed have an effect in treating covid-19 but the clinical benefit of dexamethasone is more evident in males. Here we propose a testable hypothesis that dexamethasone may be effective in men better than female owing to two factors the first is the ability of males to induce high secretion of adrenal hormone under stress vs female. In males both stressors induced a significant increase, whereas in female adrenal e excretion remained on the same level under the two stress conditions. Both Adrenal e hormones and dexamethasone are hypothesized to promote blood neutrophil levels by increasing neutrophil exit from bone marrow, delaying neutrophil outflow from circulation, and lengthening the half-life of circulating neutrophils. Neutrophils a type of white blood cells that can downregulate interferon-stimulated genes, i.e., suppress their activity. When male patients received the steroid treatment, the dysregulated interferon signals went away quickly. But in female patients, the proportions of neutrophils were not as high and they did not react to the steroids in the same way. The second factor is that ACTH response to il-6 is stronger in males than females and ACTH was found to induce il-6. Therefore, male interact with dexamethasone better than females. Additionally, dexamethasone does not affect Il-6 secreted from the adrenal cortex, which allows Il-6 to be produced during stress and increase neutrophil ratio leading to stronger response in males. We need a new classification of IL-6 at physiological and pathological aspects, as the stimulatory factors are different. it was found that ACTH is h Endocrine Il-6 is stimulated by ACTH, but immune Il-6 is stimulated by il-1β and angiotensin II. Of note, dexamethasone critically saves COVID-19 patients but has no effect on Il-6 of endocrine (ACTH stimulated) origin, either basal or stimulated. We studied the molecular docking of dexamethasone with interleukin-6 and showed that the binding interaction of dexamethasone with interleukin-6 was with high binding affinity (-6.7 Kcal/mol)

Single-cell transcriptomics of the ventral posterolateral nucleus-enriched thalamic regions from HSV-1-infected mice reveal a novel microglia/microglia-like transcriptional response

BackgroundMicroglia participate in the immune response upon central nervous system (CNS) infections. However, the role of these cells during herpes simplex encephalitis (HSE) has not been fully characterized. We sought to identify different microglia/microglia-like cells and describe the potential mechanisms and signaling pathways involved during HSE.MethodsThe transcriptional response of CD11b+ immune cells, including microglia/microglia-like cells, was investigated using single-cell RNA sequencing (scRNA-seq) on cells isolated from the ventral posterolateral nucleus (VPL)-enriched thalamic regions of C57BL/6 N mice intranasally infected with herpes simplex virus-1 (HSV-1) (6 × 105 PFUs/20 µl). We further performed scanning electronic microscopy (SEM) analysis in VPL regions on day 6 post-infection (p.i.) to provide insight into microglial functions.ResultsWe describe a novel microglia-like transcriptional response associated with a rare cell population (7% of all analyzed cells), named “in transition” microglia/microglia-like cells in HSE. This new microglia-like transcriptional signature, found in the highly infected thalamic regions, was enriched in specific genes (Retnlg, Cxcr2, Il1f9) usually associated with neutrophils. Pathway analysis of this cell-type transcriptome showed increased NLRP3-inflammasome-mediated interleukin IL-1β production, promoting a pro-inflammatory response. These cells' increased expression of viral transcripts suggests that the distinct “in transition” transcriptome corresponds to the intrinsic antiviral immune signaling of HSV-1-infected microglia/microglia-like cells in the thalamus. In accordance with this phenotype, we observed several TMEM119+/IBA-I+ microglia/microglia-like cells immunostained for HSV-1 in highly infected regions.ConclusionsA new microglia/microglia-like state may potentially shed light on how microglia could react to HSV-1 infection. Our observations suggest that infected microglia/microglia-like cells contribute to an exacerbated CNS inflammation. Further characterization of this transitory state of the microglia/microglia-like cell transcriptome may allow the development of novel immunomodulatory approaches to improve HSE outcomes by regulating the microglial immune response.

Periostin: A Potential Biomarker and Therapeutic Target in Pulmonary Diseases.

Periostin is a matricellular, nonstructural protein belonging to the fasciclin family and is encoded by the POSTN gene in humans. Periostin plays an important role in maintaining a normal tissue matrix in the lungs. Despite the vital role as a structural mediator in tissue growth and repair, periostin is involved in the pathogenic mechanism during tissue remodeling and fibrosis. Periostin is a chemoattractant mediator, promotes eosinophil recruitment and adhesion on the airways sub-epithelial membrane of asthmatic patients. POSTN gene was identified as one of the highly expressed genes induced by interleukins IL-13, IL-5 and IL-4 - the key cytokines of Th2 immune responses in the bronchial tissues of asthmatic patients. This review highlights the potential role of periostin as a validated biomarker in respiratory disease progression and its candidacy to predict the response to treatments targeting Th-2 cytokines in bronchial asthma. In addition, its potential role in COPD, IPF, lung cancer and lung infection, is also speculated. Keywords Periostin, Asthma, Pneumonia, COPD, Idiopathic pulmonary fibrosis, Biomarker.

Dietary methionine source alters the lipidome in the small intestinal epithelium of pigs

Methionine (Met) as an essential amino acid has key importance in a variety of metabolic pathways. This study investigated the influence of three dietary Met supplements (0.21% L-Met, 0.21% DL-Met and 0.31% DL-2-hydroxy-4-(methylthio)butanoic acid (DL-HMTBA)) on the metabolome and inflammatory status in the small intestine of pigs. Epithelia from duodenum, proximal jejunum, middle jejunum and ileum were subjected to metabolomics analysis and qRT-PCR of caspase 1, NLR family pyrin domain containing 3 (NLRP3), interleukins IL1β, IL8, IL18, and transforming growth factor TGFβ. Principal component analysis of the intraepithelial metabolome revealed strong clustering of samples by intestinal segment but not by dietary treatment. However, pathway enrichment analysis revealed that after L-Met supplementation polyunsaturated fatty acids (PUFA) and tocopherol metabolites were lower across small intestinal segments, whereas monohydroxy fatty acids were increased in distal small intestine. Pigs supplemented with DL-HMTBA showed a pronounced shift of secondary bile acids (BA) and sphingosine metabolites from middle jejunum to ileum. In the amino acid super pathway, only histidine metabolism tended to be altered in DL-Met-supplemented pigs. Diet did not affect the expression of inflammation-related genes. These findings suggest that dietary supplementation of young pigs with different Met sources selectively alters lipid metabolism without consequences for inflammatory status.

A microRNA panel that regulates proinflammatory cytokines as diagnostic and prognosis biomarkers in colon cancer

Colon cancer (CC) is the third most common neoplasm and the fourth cause of cancer-related death worldwide in both sexes. It has been established that inflammation plays a critical role in tumorigenesis and progression of CC. Immune, stromal and tumor cells supply the tumor microenvironment with pro-inflammatory cytokines such as interleukin 1β, TNFα, IL-6 and IL-11, to hyperactivate signaling pathways linked to cancerous processes. Recent findings suggest a putative role of microRNAs (miRNAs) in the progression and management of the inflammatory response in intestinal diseases. Moreover, miRNAs are able to regulate expression of molecular mediators that are linking inflammation and cancer. In this work a miRNA panel differentially expressed between healthy, inflammatory bowel disease (IBD) and CC tissue was established. Identified miRNAs regulate signaling pathways related to inflammation and cancer progression. An inflammation associated-miRNA panel composed of 11-miRNAs was found to be overexpressed in CC but not in inflamed or normal tissues (miR-21-5p, miR-304-5p, miR-577, miR-335-5p, miR-21-3p, miR-27b-5p, miR-335-3p, miR-215-5p, miR-30b-5p, miR-192-5p, miR-3065-5p). The association of top hit miRNAs, miR-3065-5p and miR-30b-5p expression with overall survival of CC patients was demonstrated using Kaplan-Meier tests. Finally, differential miRNA expression was validated using an inflammation-associated CC model induced by Azoxymethane/Dextran Sodium Sulfate (AOM/DSS) to compare miRNA expression in normal and inflamed tissue versus CC tissues. Based on these findings we propose the identified inflammatory miRNA panel as a potent diagnostic tool for CC determination.

Active-site molecular docking of nigellidine with nucleocapsid–NSP2–MPro of COVID-19 and to human IL1R–IL6R and strong antioxidant role of Nigella sativa in experimental rats

The recent outbreak of SARS CoV-2 has changed the global scenario of human lives/economy. A significant number of the non-survivors showed cardiac renal vasculature dysfunction. A ‘cytokine storm’ namely, interleukin IL6–IL1 receptors, i.e. IL6R–IL1R over-functioning was reported. Here, nigellidine, an indazole alkaloid and key component of Nigella sativa L. (NS) commonly known as black cumin seed was analysed for COVID-19 protein targeting and IL1R–IL6R inhibition through molecular docking study and biochemical study in experimental rat to evaluate antioxidative capacity. The NMR/X-ray crystallographic/electron microscopic structures of COVID-19 main protease (6LU7)/spike glycoprotein (6vsb)/NSP2 (QHD43415_2)/nucleocapsid (QHD43423), human IL1R (1itb)-IL6R (1pm9) from PDB were retrieved analysed for receptor–ligand interaction. Then, those structures were docked with nigellidine using AutoDock and PatchDock server. A brief comparison was made with nigellicine thymoquinone from N. sativa. Where nigellidine showed highest binding energy of −6.6 kcal/mol, ligand efficiency of −0.3 with COVID19 Nsp2 forming bonds with amino acid CYS240 present in binding pocket. Nigellidine showed strong interaction with main protease (BE: –6.38/LE: –0.29). Nigellidine showed affinity to IL1R (–6.23). The NS treated rat showed marked decline in ALP-SGPT-SGOT-malondialdehyde (MDA) than the basal levels. From the Western blot and activity analysis, it was observed that Nigellidine (sulphuryl group drug) showed no impact on phenol-catalysing ASTIV and steroid-catalysing oestrogen-sulphotransferase expressions and activities in liver tissue and thus has no influence in sulphation-mediated adverse metabolic processes. Conclusively, nigellidine has hepato-reno-protective/antioxidant-immunomodulatory/anti-inflammatory activities with inhibit potentials of COVID-19 proteins. Further validation is necessary.

Polymorphism for Interleukin-4 (-590 C/T) Promoter: Non-Association with Endometriosis

Endometriosis is a benign gynecological disorder that often occurs in women of reproductive age, usually characterized by endometrial epithelium and stroma outside their usual location. It is estimated that this disease affects 56% of women worldwide. Various types of cytokines are associated with endometriosis, including interleukin IL-4, which inhibits the production of proinflammatory cytokines that stimulate active B cells and T cell proliferation, the differentiation of B cells into plasma cells. Il-4 promoter region polymorphism (-590C/T) is involved in genetic susceptibility to endometriosis. This study aims to determine whether Gen IL-4 (-590C/T) polymorphism indicates endometriosis. This study is an analytical observational study conducted at the Laboratory of Molecular Biology in Palembang City in August 2021, with the approach of Case-Control study. There were 70 samples divided into two groups, namely 35 cases and 35 controls. Determination of genotypes and alleles using PCR-RFLP and chi-square analyzed data to determine the relationship. The results showed no significant difference. The genomorphism of the Interleukin-4(-590C/T) gene cannot be used to indicate endometriosis susceptibility.

Acquired hydrocephalus is associated with neuroinflammation, progenitor loss, and cellular changes in the subventricular zone and periventricular white matter

BackgroundHydrocephalus is a neurological disease with an incidence of 80–125 per 100,000 births in the United States. Neuropathology comprises ventriculomegaly, periventricular white matter (PVWM) alterations, inflammation, and gliosis. We hypothesized that hydrocephalus in a pig model is associated with subventricular and PVWM cellular alterations and neuroinflammation that could mimic the neuropathology described in hydrocephalic infants.MethodsHydrocephalus was induced by intracisternal kaolin injections in 35-day old female pigs (n = 7 for tissue analysis, n = 10 for CSF analysis). Age-matched sham controls received saline injections (n = 6). After 19–40 days, MRI scanning was performed to measure the ventricular volume. Stem cell proliferation was studied in the Subventricular Zone (SVZ), and cell death and oligodendrocytes were examined in the PVWM. The neuroinflammatory reaction was studied by quantifying astrocytes and microglial cells in the PVWM, and inflammatory cytokines in the CSF.ResultsThe expansion of the ventricles was especially pronounced in the body of the lateral ventricle, where ependymal disruption occurred. PVWM showed a 44% increase in cell death and a 67% reduction of oligodendrocytes. In the SVZ, the number of proliferative cells and oligodendrocyte decreased by 75% and 57% respectively. The decrease of the SVZ area correlated significantly with ventricular volume increase. Neuroinflammation occurred in the hydrocephalic pigs with a significant increase of astrocytes and microglia in the PVWM, and high levels of inflammatory interleukins IL-6 and IL-8 in the CSF.ConclusionThe induction of acquired hydrocephalus produced alterations in the PVWM, reduced cell proliferation in the SVZ, and neuroinflammation.

Inflammatory Biochemical Mediators and Their Role in Myofascial Pain and Osteopathic Manipulative Treatment: A Literature Review.

Chronic inflammatory pain conditions, specifically myofascial pain (MFP), account for an overwhelming percentage of office visits every day. The combination of the high cost of its treatment and frequent patient visits makes MFP a critical pathology to be investigated. Sharpening our understanding of the molecular mechanisms within MFP will expedite the enhancement of therapeutic approaches. Inflammation plays a critical role in the pathophysiology of MFP. The chief inflammatory mediators of interest in this review related to MFP are interleukin 1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α). This review aimed to determine the impact of inflammatory mediators on fibroblasts and satellite cells, specifically their role in muscle injury and regeneration. Blocking pro-inflammatory mediators such as IL-1β, IL-6, and TNF-α in these cell types could prove to be an effective treatment for MFP. An osteopathic manipulative treatment (OMT) modality, specifically indirect counterstrain therapy, was investigated in the hopes of elucidating a reduction in particular cytokines. In addition, myofascial release (MFR) therapies (OMT modality) were explored as a potentially effective treatment through the acceleration of wound healing, stimulation of muscle regeneration, and decreased inflammation via altered fibroblast activity. Pharmacologic agents such as non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat MFP but have a higher adverse side effect profile compared to OMT therapy. The optimal management of MFP is likely multifactorial, and more treatment modalities must be explored.This literature review analyzed 17 peer-reviewed articles specifically related to MFP management and the role of inflammation in MFP. Chronic inflammation from other etiologies was excluded. Our aim was to elucidate the biochemical mechanisms underlying MFP and inflammation in an effort to promote the medical community's understanding of treatment modalities for this chronic condition. This study revealed that various OMT techniques such as MFR and counterstrain lead to changes on the cellular level in MFP. Discovering similar effects on biochemical inflammatory markers with non-pharmacologic treatment modalities was an exciting revelation and one that could potentially change the way physicians address pain management.