Changes In Cytokines Research Articles

Integrative Analysis of Cytokine and Lipidomics Datasets Following Mild Traumatic Brain Injury in Rats.

Traumatic brain injury (TBI) is a significant source of disability in the United States and around the world and may lead to long-lasting cognitive deficits and a decreased quality of life for patients across injury severities. Following the primary injury phase, TBI is characterized by complex secondary cascades that involve altered homeostasis and metabolism, faulty signaling, neuroinflammation, and lipid dysfunction. The objectives of the present study were to (1) assess potential correlations between lipidome and cytokine changes after closed-head mild TBI (mTBI), and (2) examine the reproducibility of our acute lipidomic profiles following TBI. Cortices from 54 Sprague Dawley male and female rats were analyzed by ultra-high-performance liquid chromatography mass spectrometry (LC-MS) in both positive and negative ionization modes and multiplex cytokine analysis after single (smTBI) or repetitive (rmTBI) closed-head impacts, or sham conditions. Tissue age was a variable, given that two cohorts (n = 26 and n = 28) were initially run a year-and-a-half apart, creating inter-batch variations. We annotated the lipidome datasets using an in-house data dictionary based on exact masses of precursor and fragment ions and removed features with statistically significant differences between sham control batches. Our results indicate that lipids with high-fold change between injury groups moderately correlate with the cytokines eotaxin, IP-10, and TNF-α. Additionally, we show a significant decrease in the pro-inflammatory markers IL-1β and IP-10, TNF-α, and RANTES in the rmTBI samples relative to the sham control. We discuss the major challenges in correlating high dimensional lipidomic data with functional cytokine profiles and the implications for understanding the biological significance of two related but disparate analysis modes in the study of TBI, an inherently heterogeneous neurological disorder.

USP11 Exacerbates Radiation-Induced Pneumonitis by Activating Endothelial Cell Inflammatory Response via OTUD5-STING Signaling

PurposeRadiation induced pneumonitis (RIP) seriously limits the application of radiotherapy in the treatment of thoracic tumors, and its etiology and pathogenesis remain elusive. This study aims to elucidate the role of Ubiquitin-specific peptidase 11 (USP11) in the progression of RIP and the associated underlying mechanisms. Methods and MaterialsThe changes of cytokines and infiltrated immune cells were detected by ELISA and IHC after exposed to 20 Gy X-ray with whole thorax irradiation. USP11 expression on endothelial cell proliferation and apoptosis were analyzed by co-staining of CD31/Ki67 and CD31/Caspase-3 in vivo and the production of cytokines and ROS were confirmed by RT-PCR and flow cytometry in vitro. Comprehensive proteome and ubiquitinome were employed for USP11 substrate screening post-radiation. Results were verified by Western blot and Co-IP experiments. rAAV-lung vectors expressing OTUD5 were utilized for localized overexpression of OTUD5 in mouse pulmonary, and IHC were conducted to analyze cytokines expression. ResultsThe progression of RIP was significantly alleviated by reduced the expression of proinflammatory cytokines in both USP11 knockout (Usp11−/−) and the USP11 inhibitor mitoxantrone treated mice. Likewise, absence of USP11 resulted in decreased permeability of pulmonary vessels and neutrophils and macrophages infiltration. The proliferation rates of endothelial cells were prominently increased in the Usp11−/− lung, while the apoptosis decreased compared to the Usp11+/+ following irradiation. Conversely, USP11 overexpression increased proinflammatory cytokines and ROS production in endothelial cells post-radiation. Comprehensive proteome and ubiquitinome analyses indicated that USP11 overexpression upregulated several deubiquitinating enzymes, including USP22, USP33 and OTUD5. We clarified that USP11 deubiquitinating OTUD5 and implicate OTUD5-STING signaling pathway in the progression of inflammatory response in endothelial cells. ConclusionsUSP11 exacerbated RIP by triggering an inflammatory response in endothelial cell both in vitro and in vivo, and OTUD5-STING pathway was involved in USP11 promotes RIP. This study provided experimental support for the development of precision intervention strategies targeting USP11 to mitigate RIP.

Low-intensity pulsed ultrasound activated the anti-tumor immunity by irradiating the spleen of mice in 4 T-1 breast cancer

Tumor immunotherapy is booming around the world. However, strategies to activate the immune system and alleviate the immunosuppression still need to be refined. Here, we demonstrate for the first time that low-intensity pulsed ultrasound (LIPUS, spatial average time average intensity (Isata) is 200 mW/cm2, frequency is 0.3 MHz, repetition frequency is 1 kHz, and duty cycle is 20%) triggers the immune system and further reverses the immunosuppressive state in the mouse models of breast cancer by irradiating the spleen of mice. LIPUS inhibited tumor growth and extended survival in mice with 4 T-1 tumors. Further studies had previously shown that LIPUS enhanced the activation of CD4+ and CD8+ T cells in the spleen and led to significant changes in cytokines, as well as induced upregulation of mRNA levels involved in multiple immune regulatory pathways in the spleen. In addition, LIPUS promoted tumor-infiltrating lymphocyte accumulation and CD8+ T cell activation and improved the dynamics of cytokines/chemokines in the tumor microenvironment, resulting in a reversal of the immunosuppressive state of the tumor microenvironment. These results suggest a novel approach to activate the immune response by irradiating the spleen with LIPUS.

UNRESOLVED QUESTIONS ABOUT COATS DISEASE: A CASE REPORT

Introduction : Coats disease (CD) is an idiopathic retinal vascular disorder accompanied by retinal telangiectasia with intraretinal and/or subretinal exudation without appreciable retinal or vitreal traction. The disease most common in young males and unilateral involvement. The etiopathogenesis of CD is unclear. However, previous studies have reported changes in inflammatory cytokines, and levels of VEGF in aqueous humor are also higher in patients with CD.
 Case Illustration : We reported a 19-year-old man with complaints of decreased vision, floaters, and uncomfortable feelings in his RE, since one year before presentation. Initial examination showed visual acuity of the RE was 0.5F2 and the LE was 1.0. Examination of posterior segment showed irregularly-dilated telangiectatic vessels and exudative RD. We performed an OCT examination in both eyes and the results showed extensive cystoid macular edema in the RE. Ultrasonography of the RE also showed an exudative RD. The patient was diagnosed with Coats disease grade 3 and planned to receive intravitreal anti-VEGF injection in RE. After the second injection, OCT examination results showed no improvement in the patient's eye condition. Until now, we’re still trying to find a suitable therapy and considering laser photocoagulation.
 Discussion : Previous studies showed that there was an improvement in some CD patients only with anti-VEGF injections, but some other patients didn’t improve and had to get other additional therapy with laser photocoagulation/cryotherapy. It’s related to the severity of the disease, where a disease with grade ?3, tends to require combination therapy with laser photocoagulation/cryotherapy.
 Conclusion : Intravitreal anti-VEGF injections alone don’t show improvement in CD grade?3.

The effect of human PBMCs immobilization on their Аβ42 aggregates-dependent proinflammatory state on a cellular model of Alzheimer's disease.

The leading pathological mechanisms of Alzheimer's disease are amyloidosis and inflammation. The presented work was aimed to study the effect of human peripheral blood mononuclear cells (hPBMcs) cells-matrix adhesion on their pro-inflammatory state in vitro. Although direct interaction of Аβ42 to PBMC is not a cellular model of Alzheimer's disease, PBMCs may serve as test cells to detect Аβ42-dependent molecular effects in monitoring disease progression. Peripheral blood mononuclear cells (PBMCs) are used to assess changes in cytokines released in response to diseases or Alzheimer's disease-specific cytotoxic molecules such as Aβ42. The effect of recombinant amyloid β-peptide rАβ42 on the concentration of endogenous amyloid β-peptide Aβ40 and pro-inflammatory cytokines TNFα and IL-1β in human peripheral blood mononuclear cells that were cultured in suspension and immobilized in alginate microcarriers for 24 h were investigated. The localization and accumulation of Aβ40 and rAβ42 peptides in cells, as well as quantitative determination of the concentration of Aβ40 peptide, TNFα and IL-1β cytokines, was performed by intravital fluorescence imaging. The results were qualitatively similar for both cell models. It was determined that the content of TNFα and Aβ40 in the absence of rAβ42 in the incubation medium did not change for 24 h after incubation, and the content of IL-1β was lower compared to the cells that were not incubated. Incubation of cells in vitro with exogenous rAβ42 led to an increase in the intracellular content of TNFα and Aβ40, and no accumulation of IL-1β in cells was observed. The accumulation of Aβ40 in the cytoplasm was accompanied by the aggregation of rAβ42 on the outer surface of the cell plasma membrane. It was shown that the basic levels of indicators and the intensity of the response of immobilized cells to an exogenous stimulus were significantly greater than those of cells in suspension. To explore whether non-neuronal cells effects in alginate microcarriers were cell-matrix adhesion mediated, we tested the effect of blocking β1 integrins on proamyloidogenic and proinflammation cellular state. Immobilization within alginate hydrogels after incubation with the β1 integrins blocking antibodies showed a remarkable inhibition of TNFα and Aβ40 accumulation in rAβ42-treated cells. It can be concluded that activation of signal transduction and synthesizing activity of a portion of mononuclear cells of human peripheral blood is possible (can significantly increase) in the presence of cell-matrix adhesion.

Correlations of ADAMTS13 Expression with Kidney Injury and Inflammatory Cytokine Changes in Rats with Preeclampsia

This study investigated the altered expression of ADAMTS13 (a metalloproteinase) in a rat model of preeclampsia (PE)-induced kidney injury, along with its connection to inflammatory cytokines. Sprague-Dawley rats were divided into PE and Control groups. PE group rats were induced with Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME) to simulate PE-induced kidney injury. Key indicators such as systolic and diastolic blood pressure and proteinuria were assessed to confirm PE model success. Kidney tissue changes were examined through histology and cell apoptosis, while ADAMTS13 expression was studied using Western blotting and qRT-PCR. Plasma ADAMTS13 levels were correlated with interleukin-6 (IL-6) and IL-8 cytokines in PE rats. Elevated SBP, DBP, and proteinuria were evident in L-NAME-treated pregnant rats. Microscopic examination revealed glomerulocystic changes, thickened basement membranes, and increased apoptotic cells. Compared to Controls, PE rats exhibited decreased ADAMTS13 expression in renal tissues and plasma. Plasma IL-6 and IL-8 levels were elevated, inversely proportional to ADAMTS13 concentration in PE rats. In conclusion, PE-induced kidney injury reduced ADAMTS13 levels, correlating with heightened IL-6 and IL-8 concentrations, suggesting an interplay between ADAMTS13 and inflammatory cytokines.

Simian varicella virus infection and reactivation in rhesus macaques trigger cytokine and Aβ40/42 alterations in serum and cerebrospinal fluid.

Simian varicella virus (SVV) produces peripheral inflammatory responses during varicella (primary infection) and zoster (reactivation) in rhesus macaques (RM). However, it is unclear if peripheral measures are accurate proxies for central nervous system (CNS) responses. Thus, we analyzed cytokine and Aβ42/Aβ40 changes in paired serum and cerebrospinal fluid (CSF) during the course of infection. During varicella and zoster, every RM had variable changes in serum and CSF cytokine and Aβ42/Aβ40 levels compared to pre-inoculation levels. Overall, peripheral infection appears to affect CNS cytokine and Aβ42/Aβ40 levels independent of serum responses, suggesting that peripheral disease may contribute to CNS disease.

Age-related impact of social isolation in mice: Young vs middle-aged

Social isolation is a chronic mild stressor and a significant risk factor for mental health disorders. Herein we explored the impact of social isolation on depression- and anxiety-like behaviours, as well as spatial memory impairments, in middle-aged male mice compared to post-weaning mice. We aimed to quantify and correlate social isolation-induced behaviour discrepancies with changes in hippocampal glial cell reactivity and pro-inflammatory cytokine levels.Post-weaning and middle-aged C57BL7/J6 male mice were socially isolated for a 3-week period and behavioural tests were performed on the last five days of isolation. We found that 3 weeks of social isolation led to depressive-like behaviour in the forced swim test, anxiety-like behaviour in the open field test, and spatial memory impairment in the Morris water maze paradigm in middle-aged male mice. These behavioural alterations were not observed in male mice after post-weaning social isolation, indicating resilience to isolation-mediated stress.Increased Iba-1 expression and NLRP3 priming were both observed in the hippocampus of socially isolated middle-aged mice, suggesting a role for microglia and NLRP3 pathway in the detrimental effects of social isolation on cognition and behaviour. Young socially isolated mice also demonstrated elevated NLRP3 priming compared to controls, but no differences in Iba-1 levels and no significant changes in behaviour. Ageing-induced microglia activation and enhancement of IL-1β, TNF-α and IL-6 proinflammatory cytokines, known signs of a chronic low-grade inflammatory state, were also detected.Altogether, data suggest that social isolation, in addition to inflammaging, contributes to stress-related cognitive impairment in middle-aged mice.

The effects of Annual SZ drug on dynamic changes in lymphocytes and cytokines of COVID-19 patients: A randomized clinical trial

BackgroundThe search for a potent anti-coronavirus therapy has remained an overwhelming task since the outbreak of COVID-19. Annual SZ is a novel formulation of artemisinin and its derivatives. We aim to investigate the effect of Annual SZ on clinical outcomes, cellular immune responses, and cytokine changes in COVID-19 patients. MethodsThis study included 80 COVID-19 hospitalized patients, which were randomly allocated into two groups (intervention and control). Both groups received standard supportive treatment. In addition, the intervention group (n = 40) received Annual SZ syrup, and the control group (n = 40) received a placebo. Dynamic changes in lymphocytes, cytokines, and clinical status were evaluated since hospital admission to 7 and 14 days after treatment. ResultsThe dynamic count of total T lymphocytes and T lymphocyte subsets (CD4+ and CD8+) in the Annual SZ group was significantly higher than the placebo group (p < 0.05). In addition, Programmed Death 1 (PD-1) was significantly increased in the CD4+ and CD8+ T cells in the placebo group compared with the Annual SZ group (p < 0.05). Also, the CD4+/CD8+ ratio was not significantly different between the groups (p > 0.9). Moreover, IL-6 levels were significantly reduced (p < 0.05), while IL-4 and IFN-γ levels were not statistically different between the two groups (p > 0.05). ConclusionThis research indicated that the Annual SZ syrup significantly improved clinical status and lymphocyte frequency with less exhaustion of T lymphocytes and a reduction of inflammatory responses, which seems to be beneficial in the treatment process of COVID-19 patients.

Association of denosumab with serum cytokines, chemokines, and bone-related factors in patients with rheumatoid arthritis: A post hoc analysis of a multicentre, open-label, randomised, parallel-group study.

To clarify changes in serum cytokines, chemokines, and bone-related factors during denosumab treatment in rheumatoid arthritis (RA) patients. This was a post hoc analysis of a multicentre, open-label, randomised, parallel-group study. Patients were randomly assigned to continue treatment with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) plus receive treatment with denosumab (csDMARDs plus denosumab group) or to continue treatment with csDMARD therapy alone for 12 months. Serum biomarker levels were measured at baseline and at 6 and 12 months. Baseline and 6-month data from the csDMARDs plus denosumab (n = 22) and csDMARD therapy alone (n = 22) groups were analysed. Statistically significant changes from baseline were seen: Dickkopf-related protein 1 decreased at 6 and 12 months (both groups); osteopontin decreased at 6 months in the csDMARDs plus denosumab group; osteopontin and soluble CD40 ligand increased at 6 and 12 months in the csDMARD therapy alone group; osteocalcin decreased at 6 and 12 months, epidermal growth factor decreased at 12 months, and macrophage-derived chemokine decreased at 6 months in the csDMARDs plus denosumab group; and interferon gamma-induced protein-10 increased at 12 months in the csDMARD therapy alone group. Denosumab may inhibit bone destruction by suppressing bone-related factors/chemokines.

The study of the role of purified anti-mouse CD193 (CCR3) antibody in allergic rhinitis mouse animal models

The pathogenesis of allergic asthma is similar to that of allergic rhinitis, with inflammation cells producing and releasing inflammatory mediators and cytokines closely related to CCR3.Based on the theory of "one airway, one disease", the use of CCR3 monoclonal antibody may have a similar effect on allergic rhinitis. However, there are few studies on CCR3 monoclonal antibody in allergic rhinitis. Therefore, the aim of this study was to investigate the effective concentration of CCR3 monoclonal antibody, to compare the effects of different methods of administration, and to examine the lung condition of allergic mice to investigate whether antibody treatment protects the lungs. In this study, we constructed a mouse model of allergic rhinitis and intraperitoneally injected different doses of CCR3 monoclonal antibody (5, 10, and 20 uL/mg) to observe its therapeutic effect: observing changes in tissue morphology of nasal mucosa, infiltration of inflammation, and using ELISA to detect changes in relevant inflammatory mediators and cytokines, studying the role of CCR3 mAb in inhibiting CCR3-related actions on the nasal mucosa of allergic rhinitis mice. Furthermore, In addition, the therapeutic effects of intraperitoneal injection (i.p.) and intranasal administration (i.n.) were studied on the basis of effective concentrations.

The combined effect of oxidative stress and TRPV1 on temperature-induced asthma: Evidence in a mouse model

Temperature is one of the possible activators for asthma. As global warming continues, the health hazard of high temperatures is increasing. It is unclear, nevertheless, how high temperatures affect asthma. The research aims to examine how asthma is affected by high temperatures and underlying molecular mechanisms. The BALB/c mice were adopted in a model of asthma. The mice were exposed at 24 °C, 38 °C and 40 °C for 4h on weekdays from day 1 to day 30. After the experiment, the lung function was measured in vivo, and then serum protein, pulmonary inflammation and immunohistochemistry assay was assessed in vitro. As the temperature increased from 24 °C to 40 °C, there was a significant increase in serum protein, while there is no discernible difference in serum protein of OVA-sIgE and OVA-sIgG between the OVA (38 °C) group and OVA (24 °C) group. The immunohistochemistry assay showed a change in the pro-inflammatory cytokines. The histopathological analysis exhibited the change of airway structure after high-temperature exposure, especially for exposure at 40 °C. The results of signals protein showed a remarkable rise of TRPV1 for OVA+40 °C. Our results revealed that high temperatures may make asthmatic airway dysfunction severe, and the higher the temperature, the more serious asthma. The oxidative stress and TRPV1 receptor can be a potential drug target for asthma. It will provide a new tool for precision medicine in asthma.

Commonly disrupted pathways in brain and kidney in a pig model of systemic endotoxemia

Sepsis is a life-threatening state that arises due to a hyperactive inflammatory response stimulated by infection and rarely other insults (e.g., non-infections tissue injury). Although changes in several proinflammatory cytokines and signals are documented in humans and small animal models, far less is known about responses within affected tissues of large animal models. We sought to understand the changes that occur during the initial stages of inflammation by administering intravenous lipopolysaccharide (LPS) to Yorkshire pigs and assessing transcriptomic alterations in the brain, kidney, and whole blood. Robust transcriptional alterations were found in the brain, with upregulated responses enriched in inflammatory pathways and downregulated responses enriched in tight junction and blood vessel functions. Comparison of the inflammatory response in the pig brain to a similar mouse model demonstrated some overlapping changes but also numerous differences, including oppositely dysregulated genes between species. Substantial changes also occurred in the kidneys following LPS with several enriched upregulated pathways (cytokines, lipids, unfolded protein response, etc.) and downregulated gene sets (tube morphogenesis, glomerulus development, GTPase signal transduction, etc.). We also found significant dysregulation of genes in whole blood that fell into several gene ontology categories (cytokines, cell cycle, neutrophil degranulation, etc.). We observed a strong correlation between the brain and kidney responses, with significantly shared upregulated pathways (cytokine signaling, cell death, VEGFA pathways) and downregulated pathways (vasculature and RAC1 GTPases). In summary, we have identified a core set of shared genes and pathways in a pig model of systemic inflammation.

Elucidating the anti-inflammatory activity of platycodins in lung inflammation through pulmonary distribution dynamics and grey relational analysis of cytokines

Ethnopharmacological relevancePlatycodonis Radix (PR) is a traditional herbal remedy used to prevent and treat lung inflammation, and platycodins are speculated to be the major active constituents. However, concrete experimental verification for this assertion remains absent thus far. Aim of the studyThis study aims to compare the pulmonary distribution dynamics of five platycodins and analyze their effects on cytokines. Through the grey relational analysis (GRA) between pulmonary active components and cytokines, the study ascertains platycodins as the potential effective component against lung inflammation. Materials and methodsA rat lung inflammation model was created using lipopolysaccharides (LPS). Pulmonary distribution dynamics were analyzed via LC-MS/MS. Cytokine changes and distribution patterns in lung tissues were studied by multi-factor reagent kit. GRA was applied to determine correlations between pulmonary components and cytokines. Finally, the anti-inflammatory properties of platycodins were further studied using LPS-induced BEAS-2B cells in vitro. ResultsThe results showed that five platycodins (Platycodin D, Platycodin D3, Deapio Platycodin D, 3-O-β-D-Glucopyranosyl Platycodigenin, and Platycodigenin) featured fast absorption rate, short time to peak, and slow metabolism rate. The pulmonary distribution dynamics were significantly affected within 2 h after LPS modeling. At the same time, PR altered the relationships among different cytokines induced by LPS stimulation, particularly inflammatory cytokines IL-6 and IFN-γ. The GRA results indicated good correlation between the pulmonary distribution dynamics of the five platycodins components and the changing patterns of cytokine levels, with Platycodin D3 contributing the most. Additionally, Platycodin D3 exhibited a protective role against LPS-induced inflammation by reducing the production of pro-inflammatory mediators such as IL-1β, IL-8, and ROS, as well as increasing the expression of the anti-inflammatory mediator IL-10. ConclusionsPlatycodins are the main anti-inflammatory agents in PR and there is a good correlation with cytokines. This contributes to the anti-pneumonia effect of PR.

COVID-19-associated serum and cerebrospinal fluid cytokines in post- versus para-infectious SARS-CoV-2-related Guillain-Barré syndrome.

Guillain-Barré syndrome associated with Coronavirus-2-related severe acute respiratory syndrome (COV-GBS) occurs as para- or post-infectious forms, depending on the timing of disease onset. In these two forms, we aimed to compare the cerebrospinal fluid (CSF) and serum proinflammatory cytokine profiles to evaluate differences that could possibly have co-pathogenic relevance. We studied a retrospective cohort of 26 patients with either post-COV-GBS (n = 15), with disease onset occurring > 7days after SARS-CoV-2 infection, or para-COV-GBS (n = 11), with disease onset 7days or less. TNF-α, IL-6, and IL-8 were measured in the serum with SimplePlex™ Ella™ immunoassay. In addition to the para-/post-COV-GBS patients, serum levels of these cytokines were determined in those with non-COVID-associated-GBS (NC-GBS; n = 43), paucisymptomatic SARS-CoV-2 infection without GBS (COVID, n = 20), and in healthy volunteers (HV; n = 12). CSF cytokine levels were measured in patients with para-/post-COV-GBS, in those with NC-GBS (n = 29), or with Alzheimer's disease (AD; n = 24). Serum/CSF cytokine levels did not differ in para- vs post-COV-GBS. We found that SARS-CoV-2 infection raises the serum levels of TNF-α, IL-6, and IL-8, as well as an increase of IL-6 (in serum and CSF) and IL-8 (in CSF) in either NC-GBS or COV-GBS than controls. CSF and serum cytokine levels resulted independent one with another. The change of cytokines linked to SARS-CoV-2 in COV-GBS appears to be driven by viral infection, although it has unique characteristics in GBS as such and does not account for cases with para- or post-infectious onset.

DONOR AGE MATTERS: INTERVERTEBRAL DISC DECELLULARIZATION FOR TISSUE REGENERATION

Intervertebral disc (IVD) degeneration occurs with aging, leading to low back pain (LBP), which is one of the leading conditions of disability worldwide. With the lack of effective treatment, decellularized extracellular matrix (dECM) – based biomaterials have been proposed for IVD regeneration. However, the impact of donor ages on tissue repair had never been explored before in the disc field. Therefore, we aimed to address this question.For that, a decellularization protocol for bovine nucleus pulposus (NP) of different aged donors (fetus, young and old) was optimized by testing several detergents (SDS and Triton). The process efficiency was evaluated in terms of DNA and cell removal, as well as ECM preservation. Afterwards, dECMs were repopulated with bovine NP cells and cultured ex vivo. At day 7, cell behavior, ECM de novo synthesis and remodeling were evaluated [1]. Moreover, dECMs’ inflammatory response was assessed after in vivo CAM assay. Finally, inflammatory and angiogenic cytokines were analyzed in the conditioned media-derived from dECMs by using a cytokine array.As results, an optimal decellularization protocol (SDS 0.1%, 1h), efficient at removing cells and DNA from bovine NPs, while preserving ECM cues of native tissues, was developed. After repopulation, aggrecan increased in younger NPs, while collagen 2 decreased which may be indicative of matrix remodeling [1]. After in vivo CAM assay, fetal dECMs showed the highest inflammatory response. Finally, no statistically significant changes of cytokines were detected in the matrices, despite for a trend of higher IFN-α, IFN-γ and LIF in fetal dECMs, IL-1β in young dECMs and Decorin in old dECMs.Overall, this work uncovered the importance of tissue donor ages for tissue regenerative purpose, opening new avenues for the development of appropriate therapeutic strategies for IVD degeneration.Acknowledgments: FCT, EUROSPINE, ON Foundation.

Neuroprotective Effects of Metformin Through AMPK Activation in a Neurotoxin-Based Model of Cerebellar Ataxia.

Cerebellar ataxia is a heterogeneous group of neural disorders clinically characterized by cerebellar dysfunction. The diagnosis of patients with progressive cerebellar ataxia is complex due to the direct correlation with other neuron diseases. Although there is still no cure for this pathological condition, some metabolic, hereditary, inflammatory, and immunological factors affecting cerebellar ataxia are being studied and may become therapeutic targets. Advances in studying the neuroanatomy, pathophysiology, and molecular biology of the cerebellum (CE) contribute to a better understanding of the mechanisms behind the development of this disorder. In this study, Wistar rats aged 30 to 35 days were injected intraperitoneally with 3-acetylpyridine (3-AP) and/or metformin (for AMP-activated protein kinase (AMPK) enzyme activation) and euthanized in 24 hours and 4 days after injection. We analyzed the neuromodulatory role of the AMPK on cerebellar ataxia induced by the neurotoxin 3-AP in the brain stem (BS) and CE, after pre-treatment for 7 and 15 days with metformin, a pharmacological indirect activator of AMPK. The results shown here suggest that AMPK activation in the BS and CE leads to a significant reduction in neuroinflammation in these regions. AMPK was able to restore the changes in fatty acid composition and pro-inflammatory cytokines caused by 3-AP, suggesting that the action of AMPK seems to result in a possible neuroprotection on the cerebellar ataxia model.

Changes in Inflammatory Cytokines After Chronic Hepatitis C Treatment Among People Living With HIV.

We aimed to evaluate the effect of hepatitis C virus cure on serum inflammatory markers among people with HIV. Among 127 people with HIV, serum alanine aminotransferase, soluble tumor necrosis factor receptor 1, and inflammatory index score were significantly lower at the 24-week time point in patients who achieved sustained virologic response as compared with those who did not.

Changes in cytokines and chemokines in an acute pancreatitis model.

The immune response secondary to inflammation that develops in acute pancreatitis plays an important role in the clinical course of the disease. This study aims to evaluate the changes in various cytokines and chemokines according to the severity of pancreatitis. Twenty-one female Wistar albino rats were divided into three equal groups. The control group received no intervention. Intraperitoneal cerulein was administered to the other groups once per hour for five hours at doses of 50 µg/kg and 80 µg/kg for the mild and severe pancreatitis groups, respectively. The development of pancreatitis and its severity level were confirmed by histological evaluation after euthanization. Blood samples were taken from all rats to measure levels of Interleukin-10 (IL-10), Interferon gamma (IFN-γ), C-X-C Motif Chemokine Ligand 1 (CXCL-1), Monocyte Chemoattractant Protein-1 (MCP-1), Tumor Necrosis Factor alpha (TNF-α), Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF), IL-18, IL-12p70, IL-1β, IL-17A, IL-33, IL-1α, and IL-6. Additionally, the Schoenberg inflammation scores of pancreatic tissues were evaluated. The acute pancreatitis model was successfully induced in all cases within the study groups, according to histopathological examination. It was found that the levels of CXCL-1, MCP-1, and IL-6 were statistically significantly higher in rats with pancreatitis, with these parameters being elevated in the group with severe pancreatitis. In correlation analyses, MCP-1 and IL-6 showed a moderate correlation with the severity of pancreatitis. CXCL-1, MCP-1, and IL-6 exhibit predictive characteristics for the occurrence and clinical course of pancreatitis. Our results highlight the production and working pathways of these cytokines as potential targets for therapeutic intervention.

Neuroinflammation in comorbid depression in Alzheimer's disease: A pilot study using post-mortem brain tissue

Comorbid depression and Alzheimer's disease (AD) is associated with poorer prognosis than either condition alone. Neuroinflammation has been implicated in the pathogenesis and progression of both depression and AD, but much of the existing research has been based on peripheral blood immune markers. Relatively little is known about the neuroinflammatory environment when these conditions occur simultaneously and using immune measures directly in the brain tissue. This pilot study aimed to examine brain inflammatory marker changes in AD cases comparing those with and without comorbid depression.Post-mortem brain tissue from AD cases with depression (n = 23) and AD cases with no history of psychiatric illness (n = 25) were analyzed for a range of inflammatory markers, including markers of microglial function (Iba1, P2RY12, CD64 and CD68 measured by immunohistochemistry); endothelial inflammatory markers (ICAM-1 and VCAM-1 measured by ELISA); and cytokine levels (IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, and TNF-α measured using Mesoscale Discovery Multiplex Assays).Brains of AD cases with comorbid depression, compared with AD alone, had increased IL-4 in the superior frontal gyrus and increased TNFα & IL-12p70 in the insula. Levels of all other inflammatory markers including markers of microglial function and endothelial inflammation were similar between the two groups.We found no consistent changes in cytokines between the two brain regions in individuals with comorbid depression in AD. Further work in larger cohorts is needed to understand brain region specificity of immune marker alterations and the relationship of these changes with pre-mortem clinical outcomes.