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AbstractThis study aimed to evaluate the anti-inflammatory activity of the combination of Ardisia humilis Vahl. and Curcuma xanthorrhiza Roxb. (AC) extract in monosodium iodoacetate (MIA)-induced osteoarthritis (OA) rat model. AC was administered orally to OA rats (240, 480, and 960 mg/kg bw) for three weeks. The control and model groups comprised OA rats treated with diclofenac sodium and carrier, respectively. AC-treated rats exhibited a significant reduction in oedema volume compared to those of the model group (p < 0.05). Notably, AC, at 960 mg/kg bw, significantly decreased inflammatory cytokines TNF-α and IL-1β, along with matrix metalloproteinase-9 (MMP-9) levels compared to those of the model group (p < 0.05). AC's attenuation of OA progression was also observed through haematoxylin and eosin (H&E) and Safranin O-fast green analysis. A phytochemical study showed AC contained phenolic, flavonoid, curcumin, demethoxycurcumin, and bisdemethoxycurcumin compounds. This study concludes that AC alleviated OA progression through anti-inflammatory effects and depressed MMP-9 levels. [ABSTRACT FROM AUTHOR]

Interleukin-37 (IL-37), previously known as IL-1F7, is a member of the IL-1 family of cytokines. There are five basic subtypes of IL-37, including IL-37a, IL-37b, IL-37c, IL-37d, and IL-37e. Like other members of the IL-1 family, IL-37 is initially expressed as an immature precursor protein that needs to be processed enzymatically by caspase-1 to generate the bioactive protein. However, unlike most other members of the IL-1 family, IL-37 induces anti-inflammatory activities in IL-37 receptor-positive target cells. IL-37 functions as an extracellular protein by binding to the IL-18 receptor, IL-18R, and an intracellular protein via its interaction with SMAD family member-3 (SMAD-3). This article reviews recent findings regarding the IL-37 protein maturation process and the biological functions mediated by this cytokine.

Studying cytokine profiling in Theleria annulata infection enhances our understanding of how the immune response unfolds, the intricate interactions between the host and the parasite, the strategies employed by the parasite to evade the immune system, and potential avenues for developing treatments. The generation of pro-inflammatory cytokines plays a pivotal role in the immune response against T. annulata infection. Elevated concentrations of these cytokines potentially contribute to the manifestation of clinical symptoms associated with the disease, such as fever, anemia, exophthalmia, and weight loss. The production of anti-inflammatory cytokines potentially serves as a regulatory mechanism for the immune response, preventing the development of severe disease. Nevertheless, in animals afflicted by T. annulata infection, there is often a notable decrease in the levels of these cytokines, suggesting that they may not be as effective in mitigating the disease as they are in uninfected animals. This knowledge can be harnessed to develop improved diagnostic methods, treatments, and vaccines for tropical theileriosis. The objective of this current mini review is to achieve the same goal by consolidating the available knowledge of cytokine interactions in Bovine Tropical Theileriosis (BTT). [ABSTRACT FROM AUTHOR]

Background: Periodontitis is a chronic inflammatory condition that affects the tissues supporting the teeth, ultimately leading to tooth loss. Mesenchymal stem cells (MSCs) and their extracellular vesicles (EVs) play a crucial role in periodontitis by modulating the activities of gum cells and the immune system.Objective: To investigate the therapeutic potential of human umbilical cord mesenchymal stem cells (hUCSCs) and EVs in regulating the inflammatory response associated with periodontitis.Methods: hUCSCs were isolated, subjected to flow cytometry analysis of surface markers, and differentiated into adipocyte and osteocyte. hUCSC-EVs were isolated and characterized using flow cytometry and electron microscopy. A periodontitis animal model was established in 30 female C57Bl/6 mice. Experimental groups received hUCSCs or hUCSCs-EVs, or vehicles intravenously. Animals were monitored for 4 weeks, and the periodontal tissues were used to assess the effects of hUCSCs and hUCSCs-EVs on the expression of pro- (TNF-α, IFN-γ, and IL-17a) and anti-inflammatory cytokines (TGF-β, IL-10, and IL-4). The secretion of these cytokines by splenocytes was also evaluated using ELISA.Results: The levels of IL-17a, IFN-γ, and TNFα significantly reduced, while TGF-β and IL-10 significantly increased in the periodontal tissues of the hUCSC and hUCSCEVs-treated mice. The expression of TNF-α, IFN-γ, and IL-17a significantly decreased, while the production of IL-10 and TGF-β significantly increased in splenocytes from the hUCSC and EVs-treated mice.Conclusion: hUCSCs and their EVs have the potential to attenuate the inflammatory response associated with periodontitis, possibly by downregulating pro-inflammatory cytokines and upregulating anti-inflammatory ones.

Aim: Previous studies based on a relatively limited number of subjects have indicated potential associations between plasma cytokine concentrations in perinatal women and postpartum depression (PPD). This report aimed to examine alterations in cytokine levels during pregnancy and after delivery by measuring nine cytokines in prenatal and postnatal plasma samples in a large cohort. Methods: A nested, case–control study was conducted using plasma samples from 247 women with PPD (Edinburgh Postnatal Depression Scale: EPDS ≥9) and 243 age‐matched control (EPDS ≤2) women from among perinatal women who participated in the Tohoku Medical Megabank three‐generation cohort. Concentrations of nine plasma cytokines (IFN‐γ, IL‐1β, IL‐4, IL‐6, IL‐10, IL‐12p40, IL‐12p70, IL‐13, and TNF‐α) in plasma collected at the time of enrollment during pregnancy and 1 month after delivery were determined using an immunoassay kit. Results: Cross‐sectional comparisons of cytokine levels during pregnancy and after delivery indicated that the PPD group maintained significantly lower plasma IL‐4 levels during pregnancy and after delivery than the control group, and that plasma IL‐4 levels decreased significantly during pregnancy regardless of PPD status. Plasma IL‐10 levels were significantly higher during pregnancy than after delivery only among healthy controls, and plasma IL‐10 levels were significantly higher in the control group than in the PPD group. Moreover, IFN‐γ, IL‐6, IL‐12p40, and TNF‐α levels were significantly lower during pregnancy compared with after delivery regardless of PPD status. Conclusions: These results suggest a potential protective effect of the anti‐inflammatory cytokines IL‐4 and IL‐10 during pregnancy against the development of PPD. [ABSTRACT FROM AUTHOR]

Interleukin-37 is a newly discovered cytokine that plays a pivotal role in suppressing innate inflammation and acquired immunity. We have recently expressed both the mature(mat-) and pro-forms of human IL-37b in plants and demonstrated that while both forms of the plant-made hIL-37b are functional, pmat-hIL37b exhibited significantly greater activity than ppro-IL-37b. Compared to ppro-hIL-37b, on the other hand, the expression level of pmat-hIL-37b was substantially lower (100.5 µg versus 1.05 µg/g fresh leaf mass or 1% versus 0.01% TSP). Since the difference between ppro-hIL-37b and pmat-hIL-37b is that ppro-hIL-37b contains a signal sequence not cleavable by plant cells, we reasoned that this signal sequence would play a key role in stabilizing the ppro-hIL-37b protein. Here, we describe a novel approach to enhancing pmat-hIL-37b production in plants based on incorporation of a gene sequence encoding tobacco etch virus (TEV) protease between the signal peptide and the mature hIL-37b, including a TEV cleavage site at the C-termini of TEV protease. The rationale is that when expressed as a sp-TEV-matIL-37b fusion protein, the stabilizing properties of the signal peptide of pro-hIL-37b will be awarded to its fusion partners, resulting in increased yield of target proteins. The fusion protein is then expected to cleave itself in vivo to yield a mature pmat-hIL-37b. Indeed, when a sp-TEV-matIL-37b fusion gene was expressed in stable-transformed plants, a prominent band corresponding to dimeric pmat-hIL-37b was detected, with expression yields reaching 42.5 µg/g fresh leaf mass in the best expression lines. Bioassays demonstrated that plant-made mature pmat-hIL-37b is functional. [ABSTRACT FROM AUTHOR]

Introduction: Astrocytes play crucial role in modulating immune response in the damaged central nervous system. Numerous studies have investigated the relationship between immune responses in astrocytes and brain diseases. However, the potential application of nanomaterials for alleviating neuroinflammation induced by astrocytes remains unexplored.Method: In this study, we utilized electrophoretic deposition (EPD) to coat graphene oxide (GO) onto titanium (Ti) to enhance the bioactivity of Ti.Results: We confirmed that GO-Ti could improve cell adhesion and proliferation of astrocytes with upregulated integrins and glial fibrillary acidic protein (GFAP) expression. Moreover, we observed that astrocytes on GO-Ti exhibited a heightened immune response when exposed to lipopolysaccharide (LPS). Although pro-inflammatory cytokines increased, anti-inflammatory cytokines and brain-derived neurotrophic factors involved in neuroprotective effects were also augmented through nuclear localization of the yes-associated protein (YAP) and nuclear factor kappa B (NF‐κB).Discussion: Taken together, GO-Ti could enhance the neuroprotective function of astrocytes by upregulating the expression of anti-inflammatory cytokines and neuroprotective factors with improved cell adhesion and viability. Consequently, our findings suggest that GO-Ti has the potential to induce neuroprotective effects by regulating cell activity.

Objective To explore the effects of two doses of tranexamic acid (TXA) on postoperative bleeding and anti-inflammatory cytokine interleukin-10 (IL-10) levels in patients undergoing cardiac surgery under cardiopulmonary bypass (CPB) .Methods A total of 101 patients from Fuwai Hospital, Chinese Academy of Medical Sciences who underwent elective coronary artery bypass grafting or valve surgery under CPB were randomly divided into the low dose group (n=49) and the high dose group (n=52) .In the low dose group, a bolus dose of 20 mg/kg TXA and a maintenance dose of 15 mg/ (kg·h) were administered intravenously.While the high dose group, a bolus dose of 30 mg/kg TXA and 20 mg/ (kg·h) maintenance dose.Twenty patients in each group were selected in sequence, and the plasma IL-10 concentration was measured at four time points: before operation (T1),at the end of operation (T2),at 6 h (T3) and at 24 h (T4) after operation.In addition, postoperative blood loss, blood transfusion and the incidence of mortality and adverse events were recorded.Results Compared with the low dose group, the amount of postoperative bleeding in the high dose group was significantly reduced (P＜0.01),but there was no statistical difference in the volume of allogeneic transfusion as well as the transfusion rate (P＞0.05) .There was no statistically significant difference in IL-10 levels between the two groups at each time point of T1,T2,T3 and T4 (P＞0.05),and no statistically significant difference in the incidence of complications and adverse reactions between the two groups (P＞0.05) .Conclusion Compared with the low dose, TXA in high dose can effectively reduce postoperative bleeding after open heart surgery under cardiopulmonary bypass, but there is no significant difference in the level of anti-inflammatory factor IL-10 between the two doses. [ABSTRACT FROM AUTHOR]

Crocetin is a natural carotenoid dicarboxylic acid derived from Crocus sativus. It has been utilized as natural biomedicine with healing effects. The immunoregulatory and anti‐inflammatory properties may cause the biological activities of crocetin. Nevertheless, it is not still clear how this compound acts and causes an immune‐modulatory impact on human lymphocytes. The effects of three concentrations (5, 10, and 20 μM) of crocetin or dexamethasone (0.1 mM) were assessed on gene expression and secretion of cytokines, nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) level, and nitric oxide (NO) production in phytohaemagglutinin (PHA)‐stimulated and non‐stimulated lymphocytes. By incubation with PHA, gene expression and cytokine concentration comprising interferon (IFN)‐γ, interleukin (IL)‐17A, IL‐10, and IL‐4 were increased, along with NF‐κB concentration and NO production (all, p < 0.001). In comparison with the controls, an alteration occurred in the T‐helper (Th)2/Th1 and Th17/Treg balance in the stimulated lymphocyte toward a Th2 and Th17 response. In stimulated cells, crocetin and dexamethasone decreased pro‐inflammatory significantly and increased anti‐inflammatory cytokines and related gene expression, respectively. Moreover, Th17/Treg and Th1/Th2 balance was changed toward Treg and Th1 significantly reducing NF‐κB and NO levels (p < 0.05 to p < 0.001). Promoting effects were represented by crocetin on T‐cell subsets to Treg and Th1. Hence, it can have therapeutic value for treating predominant diseases of Th2 or Th17 cells. [ABSTRACT FROM AUTHOR]

Introduction: Interleukin-10 (IL-10) is a major anti-inflammatory cytokine, which plays an important role in regulating inflammatory responses of the immune system. Changes in IL-10 level and its function can cause an imbalance in immune response, which can be associated with various disease conditions. Aim: To study the influence of vitamin D status and IL-10 gene promoter polymorphism (rs1800871) on circulating IL-10 cytokine levels in apparently healthy South Indian population. Materials and Methods: A cross-sectional study was conducted at the Department of Clinical Pharmacology, JIPMER, Puducherry, India from January 2016 to December 2017. Apparently healthy South Indian volunteers (N=101) of either sex, age more than 18 years, were recruited for the study, after obtaining written informed consent. Serum 25-hydroxy vitamin D and plasma IL-10 levels were measured by using Chemiluminescence and Enzyme Linked Immunosorbent Assay (ELISA), respectively. IL-10 rs1800871 genotyping was performed by Real Time-polymerase Chain Reaction (RT-PCR). Values were expressed as median, Interquartile Range (IQR) and proportions were described as number with percentage. Results: The median serum vitamin D and plasma IL-10 levels observed among the study population were 18.21 ng/mL IQR, 11.3-23.08 ng/mL) and 9.04pg/mL (IQR, 7.75, 11.34 pg/mL) respectively. The genotype and allele frequencies of rs1800871 were consistent with that of the African, South Asian population of 1000 genome project. Plasma IL-10 levels were not significantly different across genotypes (p-value=0.091), even though the median level among homozygous mutant (TT) volunteers was observed to be less (8.35 pg/mL vs 9.69 pg/mL, 9.83 pg/mL). The correlation between vitamin D and IL-10 levels was observed to be insignificant (p-value=0.143). Conclusion: The present study has reported the rs1800871 genotype frequency, circulating serum vitamin D levels and plasma IL-10 levels in the apparently healthy South Indian population. IL-10 cytokine levels were not significant across the different genotype and vitamin D status groups. No significant correlation was observed between the IL-10 and vitamin D levels among the sample studied. [ABSTRACT FROM AUTHOR]

Introduction: Interleukin-10 (IL-10) is a major anti-inflammatory cytokine, which plays an important role in regulating inflammatory responses of the immune system. Changes in IL-10 level and its function can cause an imbalance in immune response, which can be associated with various disease conditions. Aim: To study the influence of vitamin D status and IL-10 gene promoter polymorphism (rs1800871) on circulating IL-10 cytokine levels in apparently healthy South Indian population. Materials and Methods: A cross-sectional study was conducted at the Department of Clinical Pharmacology, JIPMER, Puducherry, India from January 2016 to December 2017. Apparently healthy South Indian volunteers (N=101) of either sex, age more than 18 years, were recruited for the study, after obtaining written informed consent. Serum 25-hydroxy vitamin D and plasma IL-10 levels were measured by using Chemiluminescence and Enzyme Linked Immunosorbent Assay (ELISA), respectively. IL-10 rs1800871 genotyping was performed by Real Time-polymerase Chain Reaction (RT-PCR). Values were expressed as median, Inter quartile Range (IQR) and proportions were described as number with percentage. Results: The median serum vitamin D and plasma IL-10 levels observed among the study population were 18.21 ng/ mL IQR, 11.3-23.08 ng/mL) and 9.04pg/mL (IQR, 7.75, 11.34 pg/mL) respectively. The genotype and allele frequencies of rs1800871 were consistent with that of the African, South Asian population of 1000 genome project. Plasma IL-10 levels were not significantly different across genotypes (p-value=0.091), even though the median level among homozygous mutant (TT) volunteers was observed to be less (8.35 pg/mL vs 9.69 pg/mL, 9.83 pg/mL). The correlation between vitamin D and IL-10 levels was observed to be insignificant (p-value=0.143). Conclusion: The present study has reported the rs1800871 genotype frequency, circulating serum vitamin D levels and plasma IL-10 levels in the apparently healthy South Indian population. IL-10 cytokine levels were not significant across the different genotype and vitamin D status groups. No significant correlation was observed between the IL-10 and vitamin D levels among the sample studied.

Recently, many clinical trials have challenged the efficacy of current therapeutics for neuropathic pain after spinal cord injury (SCI) due to their life-threatening side-effects including addictions. Growing evidence suggests that persistent inflammatory responses after primary SCI lead to an imbalance between anti-inflammation and pro-inflammation, resulting in pathogenesis and maintenance of neuropathic pain. Conversely, a variety of data suggest that inflammation contributes to regeneration. Herein, we investigated long-term local immunomodulation using anti-inflammatory cytokine IL-10 or IL-4-encoding lentivirus delivered from multichannel bridges. Multichannel bridges provide guidance for axonal outgrowth and act as delivery vehicles. Anti-inflammatory cytokines were hypothesized to modulate the pro-nociceptive inflammatory niche and promote axonal regeneration, leading to neuropathic pain attenuation. Gene expression analyses demonstrated that IL-10 and IL-4 decreased pro-nociceptive genes expression versus control. Moreover, these factors resulted in an increased number of pro-regenerative macrophages and restoration of normal nociceptors expression pattern. Furthermore, the combination of bridges with anti-inflammatory cytokines significantly alleviated both mechanical and thermal hypersensitivity relative to control and promoted axonal regeneration. Collectively, these studies highlight that immunomodulatory strategies target multiple barriers to decrease secondary inflammation and attenuate neuropathic pain after SCI.

Helicobacter pylori (H. pylori) is one of most commonly found pathogen in the stomach. In spite of emergence of different treatment strategies, H. pylori infection remains difficult to treat. The bioengineered probiotic lactobacilli that could displace H. pylori and simultaneously present immunogenic peptides such as heparan sulphate binding protein (Hsbp) to elicit immune response could emerge as a potential therapeutic agent. The aim of this study was to discover the anti-H. pylori activities and faster exclusion of H. pylori from host cells by the recombinant strain of Lactobacillus expressing the immunogenic Hsbp protein. The results were promising and showed a 65% reduction in H. pylori adhesion after two hours of pre-incubation with recombinant-LGG and HeLa S3 cells, followed by the adhesion of H. pylori pathogen (P < 0.002). Additionally, 36% and 39% reduction were examined in co-incubation and post-incubation with recombinant-LGG, respectively. When challenged with H. pylori, the proinflammatory cytokine expression was also down regulated in recombinant-LGG treated HeLa S3 cells. This promising result provides a new insight of bioengineered probiotic lactobacilli which could displace H. pylori and simultaneously has immunogenic properties thereby may be useful to prevent H. pylori infection. [ABSTRACT FROM AUTHOR]

Abstract Background This study aims to determine and compare the effects of exercise modalities with different intensities on the secretion of key inflammation and hypoxia markers in amateur athletes. Methods Twenty-three athletes with a mean age of 20.1 years, living at low altitude (1850 m) participated in this study. The participants' maximal oxygen consumption values (VO2 max) were determined with an incremental cycle exercise test as 54.15 ± 6.14 mL kg min−1. Athletes performed four protocols: at rest, 50% VO2 max, 75% VO2 max and 100% VO2 max (until exhaustion) with one-week intervals. 50% VO2 max, 75% VO2 max sessions were performed continuously for 30 min on a bicycle ergometer and 100% VO2 max session was performed by cycling until exhaustion. Blood samples were obtained at rest and immediately after each exercise session. Serum tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP), interleukin-10 (IL-10), and hypoxia inducible factor-1 alpha (HIF-1α) levels were measured. Results There were significant differences in serum TNF-α levels in 75% VO2 max and 100% VO2 max sessions (489.03 ± 368.37 and 472.70 ± 365.21 ng/L, respectively) compared to rest conditions (331.65 ± 293.52 ng/L). Serum CRP levels of 50% VO2 max and 75% VO2 max sessions (1.19 ± 0.50; 1.07 ± 0.52 mg/L) were significantly higher than the rest condition (0.74 ± 0.35 mg/L). There were significant differences in serum IL-10 levels of rest condition and 50% VO2 max; 50% VO2 max, and 100% VO2 max sessions (328.09 ± 128.87; 446.36 ± 142.84; 347.44 ± 135.69; 324.88 ± 168.06 pg/mL). Serum HIF-1α levels were significantly higher in 75% VO2 max session compared to rest (1.26 ± 0.16; 1.08 ± 0.19 ng/mL) (P

The immune system involves several immune response mechanisms that are essential for the body to remain in balance and protected. Among these mechanisms, there is the expression of anti-inflammatory and immunomodulatory cytokines, such as interleukin-10 (IL-10). This anti-inflammatory cytokine plays a crucial role in the immune system, since it performs numerous biological functions. Studies have shown that photobiomodulation therapy (PBMT) has been effective in modulating the cytokine IL-10, increasing its expression, in various diseases of an inflammatory character. Although the mechanism of action of PBMT is not yet fully understood, it has been shown to be a promising therapy for these diseases. Therefore, the objective of this work was to review clinical studies in which they evaluated the release / expression of the cytokine IL-10 in several pathologies in response to PBMT, and to discuss the current and potential evidences of photobiomodulation.

Sepsis defined as a dysregulated immune response is a major cause of morbidity in children. In sub-Saharan Africa, the clinical features of sepsis overlap with other frequent infections such as malaria, thus sepsis is usually misdiagnosed in the absence of confirmatory tests. Therefore, it becomes necessary to identify biomarkers that can be used to distinguish sepsis from other infectious diseases. We measured and compared the plasma levels of 18 cytokines (Th1 [GM-CSF, IFN-γ, TNF-α, IL-1β, 1L-2, IL-6, IL-8, IL-12/IL-23p40, IL-15], Th2[IL-4, IL-5, IL-13), Th17 [IL17A], Regulatory cytokine (IL-10) and 7 chemokines (MCP-1/CCL2, MIP-1α/CCL3, MIP-1β/CCL4, RANTES/CCL5, Eotaxin/CCL11, MIG/CXCL9 and IP-10/CXCL10 using the Human Cytokine Magnetic 25-Plex Panel in plasma samples obtained from children with sepsis, clinical malaria and other febrile conditions. Children with sepsis had significantly higher levels of IL-1β, IL-12 and IL-17A compared to febrile controls but lower levels of MIP1-β/CCL4, RANTES/CCL5 and IP10/CXCL10 when compared to children with malaria and febrile controls. Even though levels of most inflammatory responses were higher in malaria compared to sepsis, children with sepsis had a higher pro-inflammatory to anti-inflammatory ratio which seemed to be mediated by mostly monocytes. A principal component analysis and a receiver operator characteristic curve analysis, identified seven potential biomarkers; IL-1β, IL-7, IL-12, IL-1RA, RANTES/CCL5, MIP1β/CCL4 and IP10/CXCL10 that could discriminate children with sepsis from clinical malaria and other febrile conditions. The data suggests that sepsis is associated with a higher pro-inflammatory environment. These pro-inflammatory cytokines/chemokines could further be evaluated for their diagnostic potential to differentiate sepsis from malaria and other febrile conditions in areas burdened with infectious diseases. [ABSTRACT FROM AUTHOR]

The aim of the experiment was to investigate the effects of treadmill exercise on postthoracotomy pain and the expression of spinal pro-inflammatory and anti-inflammatory cytokines. Animals were randomly distributed into four groups: (a) sham surgery, (b) rats following 60 min thoracotomy and rib retraction (thoracotomy), (c) thoracotomy rats received treadmill training (thoracotomy+treadmill), and (d) sham surgery rats received treadmill training (sham surgery+treadmill). Treadmill workouts were started on postoperative day 10 (POD10) and lasted for 6 weeks (5 days per week). Rats were examined for cold allodynia using acetone and mechanical allodynia using von Frey hairs (in grams) at the surgical site. Spinal pro-inflammatory and anti-inflammatory cytokines were analyzed on PODs 28 and 49. Both thoracotomy and thoracotomy+treadmill groups exhibited a decrease in mechanical force thresholds (g) and an increase in scratches per min on POD10. Mechanical hypersensitivity and incremental scratches lasted from POD14 and POD49 in the thoracotomy group. Although force thresholds and scratches remained not return to baseline, incremental force thresholds (p < 0.001) and diminutive scratches (p < 0.001) occurred after 6-week treadmill workouts. The rise in spinal interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) concentrations or the decline in spinal IL-10 concentration in thoracotomy+treadmill rats was less (p < 0.05) than thoracotomy rats without exercise. Mechanical allodynia using von Frey filament testing and cold allodynia by acetone testing were improved in thoracotomy rats after treadmill workouts.. Treadmill exercise restrained excess pro-inflammatory cytokine expression but increased anti-inflammatory cytokine level in a rib retraction model. [ABSTRACT FROM AUTHOR]

Sepsis defined as a dysregulated immune response is a major cause of morbidity in children. In sub-Saharan Africa, the clinical features of sepsis overlap with other frequent infections such as malaria, thus sepsis is usually misdiagnosed in the absence of confirmatory tests. Therefore, it becomes necessary to identify biomarkers that can be used to distinguish sepsis from other infectious diseases. We measured and compared the plasma levels of 18 cytokines (Th1 [GM-CSF, IFN-γ, TNF-α, IL-1β, 1L-2, IL-6, IL-8, IL-12/IL-23p40, IL-15], Th2[IL-4, IL-5, IL-13), Th17 [IL17A], Regulatory cytokine (IL-10) and 7 chemokines (MCP-1/CCL2, MIP-1α/CCL3, MIP-1β/CCL4, RANTES/CCL5, Eotaxin/CCL11, MIG/CXCL9 and IP-10/CXCL10 using the Human Cytokine Magnetic 25-Plex Panel in plasma samples obtained from children with sepsis, clinical malaria and other febrile conditions. Children with sepsis had significantly higher levels of IL-1β, IL-12 and IL-17A compared to febrile controls but lower levels of MIP1-β/CCL4, RANTES/CCL5 and IP10/CXCL10 when compared to children with malaria and febrile controls. Even though levels of most inflammatory responses were higher in malaria compared to sepsis, children with sepsis had a higher pro-inflammatory to anti-inflammatory ratio which seemed to be mediated by mostly monocytes. A principal component analysis and a receiver operator characteristic curve analysis, identified seven potential biomarkers; IL-1β, IL-7, IL-12, IL-1RA, RANTES/CCL5, MIP1β/CCL4 and IP10/CXCL10 that could discriminate children with sepsis from clinical malaria and other febrile conditions. The data suggests that sepsis is associated with a higher pro-inflammatory environment. These pro-inflammatory cytokines/chemokines could further be evaluated for their diagnostic potential to differentiate sepsis from malaria and other febrile conditions in areas burdened with infectious diseases.

The subacromial bursa (SAB) plays an important role in the tendon healing process. Based on previous reports, co-culture of the rotator cuff (RC) and SAB have been shown to increase the tendon-related gene expressions, inflammatory cytokines, and tensile strength. However, the nature of the specific biochemical alterations during the inflammatory and repair phases of tendon healing with or without the SAB remain unknown. Using a full-thickness RC tear rat model, we determined how the presence or absence of the SAB alters the histological characteristics and gene expressions. After 3 and 6 weeks, tissues were collected for histological and real-time quantitative polymerase chain reaction (RT-qPCR) evaluations. Results showed greater cell density at 3 weeks, neovascularization and tendon thickening at 6 weeks with SAB preservation. Immunostaining revealed significant increases in type 3 collagen (COL3) expression at 6 weeks with SAB preservation. The RT-qPCR results showed that SAB preservation induced significant increases in the expression of scleraxis, matrix metalloproteinase-13 (MMP-13), interleukin-1β (IL-1β), and inducible nitric oxide synthase (iNOS) at 3 weeks and significant increases in COL3, IL-10, and arginase-1 (Arg-1) at 6 weeks. An RC tear undergoes more appropriate inflammatory and repair phases during the tendon healing process when the SAB is retained. [Display omitted] • Preservation of the SAB promotes cell growth around the injury site and the formation of new blood vessels. • Preservation of the SAB increased inflammatory cytokine expressions at 3 weeks. • Preservation of the SAB increased anti-inflammatory cytokine expressions at 6 weeks. [ABSTRACT FROM AUTHOR]

Atherosclerosis progression is a result of chronic and non-resolving inflammation, effective treatments for which still remain to be developed. We designed and developed branched poly(ß-amino ester) nanoparticles (NPs) containing plasmid DNA encoding IL-10, a potent anti-inflammatory cytokine to atherosclerosis. The NPs (NP-VHPK) are functionalized with a targeting peptide (VHPK) specific for VCAM-1, which is overexpressed by endothelial cells at sites of atherosclerotic plaque. The anionic coating affords NP-VHPK with significantly lower toxicity than uncoated NPs in both endothelial cells and red blood cells (RBCs). Following injection of NP-VHPK in ApoE−/− mice, Cy5-labelled IL-10 significantly accumulates in both whole aortas and aortic sinus sections containing plaque compared to injection with a non-targeted control. Furthermore, IL-10 gene delivery results in an attenuation of inflammation locally at the plaque site. NP-VHPK may thus have the potential to reduce the inflammatory component of atherosclerosis in a safe and effective manner. Atherosclerosis is a chronic inflammatory disease that results in the formation of lipid-laden plaques within vascular walls. Although treatments using drugs and antibodies are now beginning to address the inflammation in atherosclerosis, neither is sufficient for long-term therapy. In this paper, we introduce a strategy to deliver genes encoding the anti-inflammatory protein interleukin-10 (IL-10) in vivo. We showed that Branched Poly(ß-aminoester) carrying the IL-10 gene are able to localize specifically at the plaque via surface-functionalized targeting moieties against inflamed VCAM-1 and/or ICAM-1 and to facilitate gene transcription by ECs to increase the local concentration of the IL-10 within the plaque. To date, there is no report involving non-viral nanotechnology to provide gene-based therapies for atherosclerosis. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract Background Diabetes mellitus type 2 (DM) may impede immune responses in tuberculosis (TB) and thus contribute to enhanced disease severity. In this study, we aimed to evaluate DM-mediated alterations in clinical, radiological and immunological outcomes in TB disease. Methods Newly diagnosed pulmonary TB patients with or without DM (TB n = 40; TB-DM n = 40) were recruited in Dhaka, Bangladesh. Clinical symptoms, sputum smear and culture conversion as well as chest radiography were assessed. Peripheral blood and sputum samples were collected at the time of diagnosis (baseline) and after 1, 2 and 6 months of standard anti-TB treatment. Blood samples were also obtained from healthy controls (n = 20). mRNA expression of inflammatory markers in blood and sputum samples were quantified using real-time PCR. Results The majority of TB-DM patients had poor glycemic control (HbA1c > 8%) and displayed elevated pulmonary pathology (P = 0.039) particularly in the middle (P

Abstract Background The immunosuppressive effects of regulatory B-cells (Bregs) and their immunosuppressive cytokines on immune responses in autoimmune disorders, mainly systemic lupus erythematosus (SLE), have been recently established. Therefore, the purpose of this article has been the exploration of the expressions of cytokines produced by B cells in newly diagnosed SLE patients. Results The findings demonstrated that the gene expression of IL-10, TGF-β, IL-35, PD-L1, and FasL was significantly up-regulated in SLE patients compared to healthy subjects (P

Background: This study aims to determine and compare the effects of exercise modalities with different intensities on the secretion of key inflammation and hypoxia markers in amateur athletes. Methods: Twenty-three athletes with a mean age of 20.1 years, living at low altitude (1850 m) participated in this study. The participants' maximal oxygen consumption values (VO2 max) were determined with an incremental cycle exercise test as 54.15 ± 6.14 mL kg min−1. Athletes performed four protocols: at rest, 50% VO2 max, 75% VO2 max and 100% VO2 max (until exhaustion) with one-week intervals. 50% VO2 max, 75% VO2 max sessions were performed continuously for 30 min on a bicycle ergometer and 100% VO2 max session was performed by cycling until exhaustion. Blood samples were obtained at rest and immediately after each exercise session. Serum tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP), interleukin-10 (IL-10), and hypoxia inducible factor-1 alpha (HIF-1α) levels were measured. Results: There were significant differences in serum TNF-α levels in 75% VO2 max and 100% VO2 max sessions (489.03 ± 368.37 and 472.70 ± 365.21 ng/L, respectively) compared to rest conditions (331.65 ± 293.52 ng/L). Serum CRP levels of 50% VO2 max and 75% VO2 max sessions (1.19 ± 0.50; 1.07 ± 0.52 mg/L) were significantly higher than the rest condition (0.74 ± 0.35 mg/L). There were significant differences in serum IL-10 levels of rest condition and 50% VO2 max; 50% VO2 max, and 100% VO2 max sessions (328.09 ± 128.87; 446.36 ± 142.84; 347.44 ± 135.69; 324.88 ± 168.06 pg/mL). Serum HIF-1α levels were significantly higher in 75% VO2 max session compared to rest (1.26 ± 0.16; 1.08 ± 0.19 ng/mL) (P < 0.05 for all comparisons). Conclusions: Both inflammatory and anti-inflammatory pathway is induced on different exercise intensities. Exercise protocols performed until exhaustion may lead to activation of inflammatory pathways and hypoxia-induced damage. [ABSTRACT FROM AUTHOR]

Current clinical strategies for the delivery of pulmonary therapeutics to the lung are primarily targeted to the upper portions of the airways. However, targeted delivery to the lower regions of the lung is necessary for the treatment of parenchymal lung injury and disease. Here, we have developed an mRNA therapeutic for the lower lung using one-component Ionizable Amphiphilic Janus Dendrimers (IAJDs) as a delivery vehicle. We deliver an anti-inflammatory cytokine mRNA, transforming growth factor-beta (TGF-β), to produce transient protein expression in the lower regions of the lung. This study highlights IAJD's potential for precise, effective, and safe delivery of TGF-β mRNA to the lung. This delivery system offers a promising approach for targeting therapeutics to the specific tissues, a strategy necessary to fill the current clinical gap in treating parenchymal lung injury and disease., Competing Interests: Conflict of Interest Statement: In accordance with the University of Pennsylvania policies and procedures and our ethical obligations as researchers, we report that V.P., D.W., D.Z., E.N.A-V, A.J.G. are named on patents and patent applications relevant to the work done in this publication. We have disclosed those interests fully to the University of Pennsylvania, and we have in place an approved plan for managing any potential conflicts arising from the licensing of our patents.

Major depressive disorder (MDD) is a prevalent psychiatric disease that involves malfunctions of different cell types in the brain. Accumulating studies started to reveal that microglia, the primary resident immune cells, play an important role in the development and progression of depression. Microglia respond to stress-triggered neuroinflammation, and through the release of proinflammatory cytokines and their metabolic products, microglia may modulate the function of neurons and astrocytes to regulate depression. In this review, we focused on the role of microglia in the etiology of depression. We discussed the dynamic states of microglia; the correlative and causal evidence of microglial abnormalities in depression; possible mechanisms of how microglia sense depression-related stress and modulate depression state; and how antidepressive therapies affect microglia. Understanding the role of microglia in depression may shed light on developing new treatment strategies to fight against this devastating mental illness. [ABSTRACT FROM AUTHOR]

Purpose: Platelet-rich fibrin (PRF) such as leucocyte-rich PRF (L-PRF) and injectable form of PRF (i-PRF) are widely used in various surgical applications. L-PRF- and i-PRF-derived cytokine variations and functional pathways are still unexplored. The aim of the study was to evaluate the expression pattern of Th1-, Th2-, and Th17-related cytokines by L-PRF and i-PRF under in vitro. Methods: Cytokine levels were evaluated using multi-analyte ELISArray kit. Using elevated level of cytokines, the protein-protein interaction and pathway were predicted by computational method. Results: The expressed cytokine levels were higher in L-PRF than in i-PRF. Specifically in L-PRF, IL8, IL2, IL6, and IL1A were expressed abundantly, whereas IL4, IL10, and IL6 were significantly high in i-PRF. Furthermore, protein-protein interaction (PPI) networks (cytokine-cytokine interactions) and pathway analyses were predicted using higher-order cytokines. PPI networks and gene ontology enrichment analysis showed functional variations between L-PRF and i-PRF. Kyoto Encyclopedia of Gene and Genome pathway analysis found that L-PRF mediates NF-k B signaling, Toll-like receptor signaling (TLR), and MAPK signaling via T-cell receptor signaling pathway. i-PRF is significantly involved in JAK-STAT signaling pathway through upregulation of STAT1. Conclusion: Our study concludes that L-PRF and i-PRF act via different pathways that confirm functional variations between them. Therefore, we speculate that L-PRF may be effective in acute phase of chronic wounds such as in diabetes mellitus and immunocompromised patients whereas i-PRF may have a better outcome in acute wounds. [ABSTRACT FROM AUTHOR]

• Systemic lupus erythematosus (SLE) is an auto-inflammatory disease that is characterized by chronic and widespread inflammation. • IL-35, the newest member of the IL-12 family, is an immunosuppressive and anti-inflammatory cytokine secreted mainly by regulatory cells. • IL-35 appears to hold therapeutic and diagnostic potential in cancer and autoimmune diseases. • IL-35 can consider as a preferential therapeutic or diagnostic candidate in SLE management. It is well known that systemic lupus erythematosus (SLE) is an auto-inflammatory disease that is characterized by chronic and widespread inflammation. The exact pathogenesis of SLE is still a matter of debate. However, it has been suggested that the binding of autoantibodies to autoantigens forms immune complexes (ICs), activators of the immune response, in SLE patients. Ultimately, all of these responses lead to an imbalance between anti-inflammatory and pro-inflammatory cytokines, resulting in cumulative inflammation. IL-35, the newest member of the IL-12 family, is an immunosuppressive and anti-inflammatory cytokine secreted mainly by regulatory cells. Structurally, IL-35 is a heterodimeric cytokine, composed of Epstein-Barr virus-induced gene 3 (EBI3) and p35. IL-35 appears to hold therapeutic and diagnostic potential in cancer and autoimmune diseases. In this review, we summarized the most recent associations between IL and 35 and SLE. Unfortunately, the comparative review of IL-35 in SLE indicates many differences and contradictions, which make it difficult to generalize the use of IL-35 in the treatment of SLE. With the available information, it is not possible to talk about targeting this cytokine for the lupus treatment. So, further studies would be needed to establish the clear and exact levels of this cytokine and its related receptors in people with lupus to provide IL-35 as a preferential therapeutic or diagnostic candidate in SLE management. [ABSTRACT FROM AUTHOR]

Dry eye disease (DED) is caused by a loss of homeostasis of the tear film, which results in visual disturbance, ocular surface inflammation and damage, and neurosensory abnormalities. Although it is prevalent in 5–50% of the global population, there are limited clinical options for its treatment. This study explored the potential use of human intravenous immunoglobulin (IVIg) and its enriched fractions of sialylation, sialylated IVIg (sIVIg), as a treatment for DED. Fifteen female New Zealand white rabbits were topically instilled with 0.2% benzalkonium chloride (BAC) twice daily for five consecutive days to induce experimental dry eye. Saline, 0.4% IVIg, or 0.04% sIVIg eye drops were instilled twice daily for 20 consecutive days. Clinical evaluations, such as non-invasive tear break-up time (NIBUT) and corneal fluorescein staining (CFS), were conducted. mRNA levels of mucin 4, mucin 16, TNF-α, IL-1β, MMP9, IL-10, TGF-β, and CD209 in rabbit conjunctival tissues were examined using reverse transcription polymerase chain reaction (RT-PCR) or quantitative RT-PCR (qRT-PCR). The relationships between CD209 family members in rabbits and various mammalian species were analyzed using a phylogenetic tree. IVIg or sIVIg treatment resulted in clinical improvements in the rabbit DED model. The inflammatory cytokines, TNF-α and IL-1β, were increased and mucin 4 and mucin 16, cell surface-associated mucins, were decreased in BAC-induced dry eye. Following IVIg or sIVIg treatment, inflammatory cytokines decreased, whereas the anti-inflammatory cytokine, IL-10, increased substantially. Moreover, a 10-fold lower sIVIg treatment dose resulted in prolonged IL-10 production, representing a significantly improved DED compared to IVIg. Furthermore, the expression of rabbit CD209 mRNA in the rabbit conjunctiva and its close relationship with primate homologs suggest that it may interact with IVIg or sIVIg to promote IL-10 expression, as previously described in humans. At a lower dosage, sIVIg showed a more efficient improvement in DED, making it a promising new candidate medication for DED. • IVIg or sIVIg treatment in the rabbit dry eye model showed higher level of clinical improvements. • Prolonged IL-10 expression in IVIg- or sIVIg-treated rabbit conjunctiva resulted in accelerated an anti-inflammatory effect. • The sIVIg treatment offers a more efficient improvement and reduced dosage requirement. • The sIVIg treatment introduces a promising new therapeutic approach for dry eye diseases. [ABSTRACT FROM AUTHOR]

Background: Diabetes mellitus type 2 (DM) may impede immune responses in tuberculosis (TB) and thus contribute to enhanced disease severity. In this study, we aimed to evaluate DM-mediated alterations in clinical, radiological and immunological outcomes in TB disease.Methods: Newly diagnosed pulmonary TB patients with or without DM (TB n = 40; TB-DM n = 40) were recruited in Dhaka, Bangladesh. Clinical symptoms, sputum smear and culture conversion as well as chest radiography were assessed. Peripheral blood and sputum samples were collected at the time of diagnosis (baseline) and after 1, 2 and 6 months of standard anti-TB treatment. Blood samples were also obtained from healthy controls (n = 20). mRNA expression of inflammatory markers in blood and sputum samples were quantified using real-time PCR.Results: The majority of TB-DM patients had poor glycemic control (HbA1c > 8%) and displayed elevated pulmonary pathology (P = 0.039) particularly in the middle (P < 0.004) and lower lung zones (P < 0.02) throughout the treatment period. However, reduction of clinical symptoms and time to sputum smear and culture conversion did not differ between the groups. Transcripts levels of the pro-inflammatory cytokines IL-1β (P = 0.003 at month-1 and P = 0.045 at month-2) and TNF-α (P = 0.005 at month-1) and the anti-inflammatory cytokine IL-10 (P = 0.005 at month-2) were higher in peripheral blood after anti-TB treatment in TB-DM compared to TB patients. Conversely in sputum, TB-DM patients had reduced CD4 (P < 0.009 at month-1) and IL-10 (P = 0.005 at month-1 and P = 0.006 at month-2) transcripts, whereas CD8 was elevated (P = 0.016 at month-2). At 1- and 2-month post-treatment, sputum IL-10 transcripts were inversely correlated with fasting blood glucose and HbA1c levels in all patients.Conclusion: Insufficient up-regulation of IL-10 in the lung may fuel persistent local inflammation thereby promoting lung pathology in TB-DM patients with poorly controlled DM. [ABSTRACT FROM AUTHOR]

The purpose of the experiment was to study the effect of pulsed ultrasound (PUS) on post-thoracotomy pain and local tissue temperature and to correlate the findings with the alteration in spinal anti-inflammatory and pro-inflammatory cytokines. Mechanical sensitivity, subcutaneous temperature and spinal interleukin-10 (IL-10), IL-6 or tumor necrosis factor-alpha (TNF-α) expression were examined in a rat model of experimental post-thoracotomy pain. Group 1 received a sham surgery where thoracotomy was performed except for rib retraction. Group 2 underwent thoracotomy with rib retraction (TRR). Group 3 received the TRR procedure followed by PUS. Group 4 underwent the TRR procedure followed by only the massage with the ultrasound turned off. Compared with group 1 (sham), groups 2-4 showed a decrease in mechanical withdrawal thresholds on postoperative days (PODs) 10 and 11. On PODs 16, 23 and 30, group 3 (TRR+PUS-1) displayed an increase in mechanical withdrawal thresholds compared with groups 2 and 4. Subcutaneous and body temperatures in group 3 were not prominently different from group 1, group 2 (TRR only) or group 4 (TRR+PUS-0). Compared with group 2, group 3 had an increase in spinal IL-10 level on POD 30 and a decrease in spinal IL-6 or TNF-α expression on PODs 16 and 30. We concluded that mechanical hypersensitivity after TRR is postponed by PUS, and its effect continues for 3 wk. A PUS dose not increase local tissue temperature. The beneficial effect of PUS appears related to upregulation of spinal anti-inflammatory cytokine and downregulation of spinal pro-inflammatory cytokines. [ABSTRACT FROM AUTHOR]

Hyper-inflammation during acute phase and sequential hypo-inflammation during immunosuppressive phase in macrophages/monocytes lead to multiorgan failure syndrome and immune collapse of sepsis, in which toll-like receptor (TLR)-triggered inflammatory responses play a major role. Here, we reported that Siglecg deficiency attenuated TLR4-triggered pro-inflammatory cytokine production and increased anti-inflammatory cytokine [interleukin-10 [IL-10]] production in vivo and in vitro at both acute and immunosuppressive phases. Siglecg deficiency also protected mice from lipopolysaccharide (LPS)-induced sepsis with less inflammation in the lung and less tissue destruction in the spleen. Siglec-G inhibited proto-oncogene tyrosine-protein kinase Src (Src) activation via recruiting and activating tyrosine phosphatase Src homology region 2 domain-containing phosphatase-1 (SHP1) through immunoreceptor tyrosine-based inhibitory motif (ITIM) domain. Src could inhibit TLR4-induced inflammatory cytokines and promote anti-inflammatory cytokine IL-10. Mechanical investigation showed that Src could interact with and phosphorylate STAT3. Src could also promote HIF1α degradation through activating GSK3β. Our study reveals that Siglec-G orchestrates TLR-induced inflammation, which outlines that blocking Siglec-G or activating Src may be a promising strategy for both acute and chronic inflammatory diseases.

Hyperactivity of the immune system in the gastrointestinal tract leads to the development of chronic, inflammation-associated disorders. Such diseases, including inflammatory bowel disease, are not completely curable, but the specific line of treatment may reduce its symptoms. However, the response to treatment varies among patients, creating a necessity to uncover the pathophysiological basis of immune-mediated diseases and apply novel therapeutic strategies. The present study describes the anti-inflammatory properties of osthole during histamine-induced inflammation in the intestinal Caco-2 cell line. Osthole reduced the secretion of cytokines (CKs) and the expression level of inflammation-associated genes, which were increased after a histamine treatment. We have shown that the secretion of pro-inflammatory CKs (IL-1β, IL-6, IL-8, and TNF-α) during inflammation may be mediated by NFκB, and, after osthole treatment, this signaling pathway was disrupted. Our results suggest a possible role for osthole in the protection against inflammation in the gastrointestinal tract; thus, osthole may be considered as an anti-inflammatory modulator.

It is questionable whether intermittent fasting (IF) protects against brain ischemic injury. This study examined whether IF increased anti-inflammatory cytokines and protected neurons from ischemia–reperfusion injury in the gerbil hippocampus. Gerbils were subjected to 1-day alternating fasting as IF for 1, 2, or 3 months and assigned to sham or 5 min of transient ischemia. We examined the changes in anti-inflammatory cytokines (IL-4 and IL-13), neurons and IgG by immunohistochemistry or immunofluorescence staining in the cornu ammonis 1 (CA1) region of the hippocampus before and after ischemia. IF increased IL-13 immunoreactivity in the CA1 region before ischemia, but did not affect IL-4 immunoreactivity. After ischemia, IL-13 and 4 immunoreactivities in the CA1 region were significantly lower in IF gerbils than in non-IF gerbils. In the IF gerbils, the CA1 pyramidal neurons were not protected from ischemic injury; in these gerbils, strong IgG immunoreactivity was seen in the CA1 parenchyma, indicating leakage of the BBB. In brief, IF increased IL-13 in the CA1 region, but these neurons were not protected from transient ischemic injury evidenced by IgG immunoreactivity in the CA1 parenchyma. This study indicates that IF increased some anti-inflammatory cytokines but did not afford neuroprotection against ischemic insults via BBB disruption. [ABSTRACT FROM AUTHOR]

Hyper-inflammation during acute phase and sequential hypo-inflammation during immunosuppressive phase in macrophages/monocytes lead to multiorgan failure syndrome and immune collapse of sepsis, in which toll-like receptor (TLR)-triggered inflammatory responses play a major role. Here, we reported that Siglecg deficiency attenuated TLR4-triggered pro-inflammatory cytokine production and increased anti-inflammatory cytokine [interleukin-10 [IL-10]] production in vivo and in vitro at both acute and immunosuppressive phases. Siglecg deficiency also protected mice from lipopolysaccharide (LPS)-induced sepsis with less inflammation in the lung and less tissue destruction in the spleen. Siglec-G inhibited proto-oncogene tyrosine-protein kinase Src (Src) activation via recruiting and activating tyrosine phosphatase Src homology region 2 domain-containing phosphatase-1 (SHP1) through immunoreceptor tyrosine-based inhibitory motif (ITIM) domain. Src could inhibit TLR4-induced inflammatory cytokines and promote anti-inflammatory cytokine IL-10. Mechanical investigation showed that Src could interact with and phosphorylate STAT3. Src could also promote HIF1α degradation through activating GSK3β. Our study reveals that Siglec-G orchestrates TLR-induced inflammation, which outlines that blocking Siglec-G or activating Src may be a promising strategy for both acute and chronic inflammatory diseases. [ABSTRACT FROM AUTHOR]

Context: Withaferin A (WFA) exhibits diverse pharmaceutical applications on human diseases, including rheumatoid arthritis, cancers and microbial infection. Objective: We evaluated the neuroprotective role of WFA using a mouse model of spinal cord injury (SCI). Materials and methods: BALB/c mice were administrated 10 mg/kg of WFA. Gene expression was measured by real-time PCR, western blot and immunohistochemistry. Cell morphology and apoptosis were determined by H&E staining and TUNEL assay. Motor function was evaluated by the BBB functional scale for continuous 7 weeks. Results: WFA significantly improved neurobehavioural function and alleviated histological alteration of spinal cord tissues in traumatized mice. Brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) significantly increased in WFA-treated mice. Meanwhile, the expression of Nogo-A and RhoA remarkably decreased in the presence of WFA. Furthermore, the apoptotic cell death was attenuated in mice treated with WFA (31.48 ± 2.50% vs. 50.08 ± 2.08%) accompanied by decreased bax and increased bcl-2. In addition, WFA decreased the expression of pro-inflammatory mediators such as IL-1β (11.20 ± 1.96 ng/mL vs. 17.59 ± 1.42 ng/mL) and TNF-α (57.38 ± 3.57 pg/mL vs. 95.06 ± 9.13 pg/mL). The anti-inflammatory cytokines including TGF-β1 (14.32 ± 1.04 pg/mL vs. 9.37 ± 1.17 pg/mL) and IL-10 (116.80 ± 6.91 pg/mL vs. 72.33 ± 9.35 pg/mL) were elevated after WFA administration. Discussion and conclusion: This study demonstrated that WFA has a neuroprotective role by inhibition of apoptosis and inflammation after SCI in mice.

Background: The article presents the influence evaluation results of the anti-inflammatory cytokine — IL10 and blood clotting factors - F2 and F5 genes polymorphism on the formation of hereditary predisposition to the development of preeclampsia in women of the Rostov region. Patients and methods: In this case-control setting, we included 101 pregnant women at 24 to 36 weeks of gestation, who were divided into two groups: the group of women with preeclampsia and the control group. All women were tested for mutations of interleukin–10 gene (IL-10), the blood coagulation factors F2 and F5 genes. Results: During the analysis of the IL-10 -592A>C (rs1800872) and -819T>C (rs3021097); F2 20210G-A (rs1799963) and F5 1691G-A (rs6025) polymorphisms contribution to genetic predisposition to preeclampsia, it was detected that carriers of the homozygous genotype of the IL-10 -592A>C polymorphic locus have an increased risk of developing this complication of pregnancy (OR=3,39; 95%CI 1.13–10.22), however, no statistically significant differences were found for the other studied loci. Conclusion: The current study results inconsistent with previous studies; showed that the IL-10 -592A>C polymorphism, but not IL-10 -819T>C, F2 20210G-A and F5 1691G-A polymorphisms, may be contributed to the susceptibility of preeclampsia in Rostov population.

Background: Periodontitis is a chronic inflammatory condition that affects the tissues supporting the teeth, ultimately leading to tooth loss. Mesenchymal stem cells (MSCs) and their extracellular vesicles (EVs) play a crucial role in periodontitis by modulating the activities of gum cells and the immune system., Objective: To investigate the therapeutic potential of human umbilical cord mesenchymal stem cells (hUCSCs) and EVs in regulating the inflammatory response associated with periodontitis., Methods: hUCSCs were isolated, subjected to flow cytometry analysis of surface markers, and differentiated into adipocyte and osteocyte. hUCSC-EVs were isolated and characterized using flow cytometry and electron microscopy. A periodontitis animal model was established in 30 female C57Bl/6 mice. Experimental groups received hUCSCs or hUCSCs-EVs, or vehicles intravenously. Animals were monitored for 4 weeks, and the periodontal tissues were used to assess the effects of hUCSCs and hUCSCs-EVs on the expression of pro- (TNF-α, IFN-γ, and IL-17a) and anti-inflammatory cytokines (TGF-β, IL-10, and IL-4). The secretion of these cytokines by splenocytes was also evaluated using ELISA., Results: The levels of IL-17a, IFN-γ, and TNFα significantly reduced, while TGF-β and IL-10 significantly increased in the periodontal tissues of the hUCSC and hUCSCEVs-treated mice. The expression of TNF-α, IFN-γ, and IL-17a significantly decreased, while the production of IL-10 and TGF-β significantly increased in splenocytes from the hUCSC and EVs-treated mice., Conclusion: hUCSCs and their EVs have the potential to attenuate the inflammatory response associated with periodontitis, possibly by downregulating pro-inflammatory cytokines and upregulating anti-inflammatory ones.

Background: While most studies focus on pro‐allergic cytokines, the protective role of immunosuppressive cytokines in allergic inflammation is not well elucidated. This study was to explore a novel anti‐inflammatory role and cellular/molecular mechanism of IL‐27 in allergic inflammation. Methods: A murine model of experimental allergic conjunctivitis (EAC) was induced in BALB/c, C57BL/6 or IL‐27Rα‐deficient (WSX‐1−/−) mice by short ragweed pollen, with untreated or PBS‐treated mice as controls. The serum, eyeballs, conjunctiva, cervical lymph nodes (CLNs) were used for study. Gene expression was determined by RT‐qPCR, and protein production and activation were evaluated by immunostaining, ELISA and Western blotting. Results: Typical allergic manifestations and stimulated thymic stromal lymphopoietin (TSLP) signaling and Th2 responses were observed in ocular surface of EAC models in BALB/c and C57BL/6 mice. The decrease of IL‐27 at mRNA (IL‐27/EBI3) and protein levels were detected in serum, conjunctiva and CLN, as evaluated by RT‐qPCR, immunofluorescent staining, ELISA and Western blotting. EAC induced in WSX‐1−/− mice showed aggravated allergic signs with higher TSLP‐driven Th2‐dominant inflammation, accompanied by stimulated Th17 responses, including IL‐17A, IL‐17F, and transcription factor RORγt. In contrast, Th1 cytokine IFNγ and Treg marker IL‐10, with their respective transcription factors T‐bet and foxp3, were largely suppressed. Interestingly, imbalanced activation between reduced phosphor (P)‐STAT1 and stimulated P‐STAT6 were revealed in EAC, especially WSX‐1−/−‐EAC mice. Conclusion: These findings demonstrated a natural protective mechanism by IL‐27, of which signaling deficiency develops a Th17‐type hyperresponse that further aggravates Th2‐dominant allergic inflammation. [ABSTRACT FROM AUTHOR]

Highlights • We construct the sialic acid deficient mutant GBS (Δ neuA). • We examine the effects of GBS infection on the expression of pro- and anti-inflammatory cytokines in OnSiglec-like-transfected macrophage RAW264 cells. • We examine the effects of GBS infection on the expression of pro- and anti-inflammatory cytokines in tilapia immune tissues. • We confirm that sialylated CPs on GBS appear to interact with host OnSiglec-like molecules to transmit negative regulatory signals via enhanced IL-10 production and reduced some pro-inflammatory cytokine production. Abstract Group B Streptococcus (GBS, S. agalactiae) infection in tilapia (Oreochromis niloticus) causes widespread death of this species and is a significant issue for the aquaculture industry. The major virulence factor for GBS is its sialylated capsular polysaccharides (CPs). These CPs interact with sialic acid-binding immunoglobulin-like lectins (Siglecs) on the host immune cells to regulate the downstream inflammatory response and evade detection. Previously, we cloned multiple Siglec-like molecules from an O. niloticus cDNA library, all of which were shown to interact with the sialylated CPs of GBS. In the present study, we investigated the effects of GBS infection on the expression of pro- and anti-inflammatory cytokines in O. niloticus as well as On Siglec-like-transfected macrophage cells. Eukaryotic expression vectors containing full-length On Siglec-1-like, -4b-like, -14-like were constructed and used to transfect RAW264 macrophages in vitro as well as live tilapia in vivo prior to GBS infection. The expression of the anti-inflammatory cytokine interleukin (IL)-10 and the pro-inflammatory cytokines tumor necrosis factor (TNF)-α , IL-6, and interferon (INF)-β were then analyzed by qPCR. Our results indicate that as infection progressed, IL-10 expression was significantly upregulated, while that of TNF-α and IL-6 were significantly downregulated in the On Siglec-like-transfected cells. INF-β expression was also downregulated in cells transfected with On Siglec-1-like and -4b-like, but was not significantly effected in On Siglec-14-like-transfected cells. Notably, the magnitude of these cytokine expression changes was greatly decreased when a Δ neuA GBS mutant was used to infect the On Siglec-1-like-transfected cells. In GBS-infected tilapia, IL-10 expression was significantly upregulated in all tissues, whereas INF-β expression in the spleen, kidney, and gills was significantly downregulated at 12 hpi. While the expression of TNF-α was slightly upregulated, this change was not significant. In GBS Δ neuA mutant-infected O. niloticus , IL-10 expression in all of the tissues was significantly lower than that observed for the wild-type GBS group, while TNF-α expression was higher in the mutant infected group. There was no significant difference in INF-β expression between the two groups. Taken together, sialylated CPs on GBS appear to interact with host On Siglec-like molecules to transmit negative regulatory signals via enhanced anti-inflammatory cytokine IL-10 production and reduced pro-inflammatory cytokine production, ultimately leading to dampening of the host immune response. The results of this study further elucidate the molecular mechanism underlying GBS infection in tilapia and also provide candidate drug target molecules. [ABSTRACT FROM AUTHOR]

Arabinoxylan (AX) has been deemed as an antinutritional factor, but limited information has addressed the effects of dietary AX on intestinal health of fish. The present study investigated the effects of dietary AX on intestinal mucosal physical and immunological barriers of rainbow trout (Oncorhynchus mykiss). Five isoproteic and isolipidic experimental diets (AXE, AX0, AX2.5, AX5 and AX10) were formulated to contain 0.03% arabinoxylanase as well as 0%, 2.5%, 5% and 10% AX, respectively. Each diet was randomly distributed to triplicate groups of 35 juvenile (average weight 3.14 ± 0.02 g) per tank in a rearing system maintained at 17 ± 1 °C for 9 weeks. Dietary AX supplementation regardless of inclusion levels significantly (P < 0.05) depressed the growth performance and feed utilization. The plasma endothelin-1 and d -lactic acid contents as well as diamino oxidase activity were significantly higher in fish fed diet AX10 compared to fish fed diet AX0. Dietary inclusion of 5–10% AX resulted in decreased intestinal villus height, goblet cell number and desmosome density, increased crypt depth, short and irregular microvilli, widened intercellular space; down-regulated the mRNA levels of occludin in hindgut, claudin3 and ZO-1 in foregut and midgut, but up-regulated the mRNA levels of claudin12 and claudin15 in midgut as well as claudin23 in foregut, midgut and hindgut. Furthermore, dietary 5–10% AX supplementation decreased the midgut and hindgut complement 3, complement 4 and sIgT contents as well as the midgut IgM and hindgut IL-10 contents. Conversely, the hindgut TNF-α and IL-6 contents increased with the rising dietary AX level. RT-qPCR demonstrated that the pro-inflammatory cytokines (IL-1β, IL-6, IL-8, IL-12β, IFN-γ, and TNF-α) and pIgR mRNA levels in midgut and hindgut were up-regulated by dietary AX inclusion of 5–10% AX. Meanwhile, the mRNA levels of p38 MAPK, IκBα, and NF-κB p65 in midgut and hindgut raised gradually with the increasing dietary AX content. The Western blot results showed that the protein expression levels of p38 MAPK and NF-κB generally increased with the rising dietary AX content. Dietary treatment with 0.03% arabinoxylanase did not affect the growth performance and intestinal health of rainbow trout (P > 0.05). In conclusion, excessive dietary AX inclusion (5–10%) increased the intestinal permeability and induced the intestinal inflammatory response via activating MAPK/NF-κB signaling pathway, and ultimately damaged the intestinal barrier function of rainbow trout. • Dietary 2.5–10% arabinoxylan exhibited the antinutritional effect on growth performance of rainbow trout. • Dietary 5–10% arabinoxylan impaired the intestinal mucosal barrier and intestinal permeability of rainbow trout. • Excessive dietary arabinoxylan damaged the intestinal mucosal physical and immunological barriers via activating MAPK/NF-κB. [ABSTRACT FROM AUTHOR]

Introduction: Knee osteoarthritis (KOA), the most common form of osteoarthritis (OA) is a considerable health concern worldwide. Platelet-rich plasma (PRP) is a common therapeutic option for KOA. Different types of PRPs have varying efficacies. However, a comparative analysis of the qualities of these PRPs is lacking. Methods: Two types of PRPs, including autologous protein solution (APS), and leukocyte-poor PRP (LP-PRP) along with whole blood (WB) and platelet-poor plasma (PPP) were characterized for platelet content, leukocyte content, and composition in 10 healthy volunteers (HV) (the controlled laboratory study) and 16 KOA patients (a retrospective observational study). Additionally, the levels of the platelet-derived growth factor (PDGF)-BB, and different cytokines were estimated in HV. Results: In HV, the concentrations of platelets and leukocytes, levels of different cytokines, including interleukin 1 receptor antagonist (IL-1Ra), soluble TNF receptor type II (sTNF-RII), and IL-1β, and the ratio of IL-1Ra/IL-1β were significantly higher in APS, whereas the PDGF-BB was higher in LP-PRP than APS. In KOA patients, a higher concentration of platelets was observed in LP-PRP, and a higher concentration of leukocytes was observed in APS than LP-PRP. Following the PAW classification system, LP-PRP was classified as P2-B type in HV (51.3 × 104/μl) and KOA (53.4 × 104/μl), whereas APS was classified as P3-A type in HV (110.1 × 104/μl) and P2-A type in KOA (29.0 × 104/μl). In a retrospective observational study, the KOA patients who underwent APS injection had a higher incidence of arthralgia, and this arthralgia lasted for a longer time than LP-PRP injection in the same individual. Discussion: The quality of the two PRPs differed distinctively depending on their preparation methods, which might affect their clinical efficacies and adverse events. Therefore, the characterization of these parameters should be prioritized while choosing PRP.

Aim: Most children under six with seizures experience febrile seizures (FS), which occur with a temperature of 38°C or higher and no apparent infectious or metabolic causes. FS has a multifaceted etiology, involving genetic and environmental factors. This study aimed to explore the connection between the cytokine system (part of the immune system related to inflammation) and FS to uncover potential relationships., Method: This research was carried out on 50 patients experiencing FS and 25 patients experiencing only fever served as cases and controls, respectively. The patient's blood was obtained under sterile circumstances from the antecubital/femoral vein as soon as feasible following the commencement of seizures. The complete hemogram analysis was done using the Mindray BC-5800 auto hematology analyzer (Mindray Medical International Limited, Shenzhen, China)., Result: The cases group had significantly higher interleukin-4 (IL-4) concentrations (292.85 pg/mL) than controls (81.04 pg/mL), indicating a statistically significant difference (p<0.05), respectively. In the current research, case participants had a significantly lower mean level of interleukin-6 (IL-6) than control participants. The average IL-6 concentration in cases was 28.00 pg/mL, whereas in controls was 93.09pg/mL. Patients with FS have an important function for the cytokine network to perform., Conclusion: The findings showed a significant difference in cytokine concentrations between patients with FS and control subjects, highlighting a potential link between the cytokine system and FS. Additionally, lower levels of IL-6 in case participants suggest a complex role of cytokines in FS, emphasizing the importance of the cytokine network in this condition., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Vishal et al.)

Introduction: Astrocytes play crucial role in modulating immune response in the damaged central nervous system. Numerous studies have investigated the relationship between immune responses in astrocytes and brain diseases. However, the potential application of nanomaterials for alleviating neuroinflammation induced by astrocytes remains unexplored. Method: In this study, we utilized electrophoretic deposition (EPD) to coat graphene oxide (GO) onto titanium (Ti) to enhance the bioactivity of Ti. Results: We confirmed that GO-Ti could improve cell adhesion and proliferation of astrocytes with upregulated integrins and glial fibrillary acidic protein (GFAP) expression. Moreover, we observed that astrocytes on GO-Ti exhibited a heightened immune response when exposed to lipopolysaccharide (LPS). Although pro-inflammatory cytokines increased, anti-inflammatory cytokines and brain-derived neurotrophic factors involved in neuroprotective effects were also augmented through nuclear localization of the yes-associated protein (YAP) and nuclear factor kappa B (NF-κB). Discussion: Taken together, GO-Ti could enhance the neuroprotective function of astrocytes by upregulating the expression of anti-inflammatory cytokines and neuroprotective factors with improved cell adhesion and viability. Consequently, our findings suggest that GO-Ti has the potential to induce neuroprotective effects by regulating cell activity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Han, Jang, Lee, Oh, Lee and Yoon.)

Interleukin-10 (IL-10) is an anti-inflammatory cytokine and negatively regulates cell-mediated immunity (CMI) induction by inhibiting cytokine production in type 1 T helper cells. IL-10 genes have been isolated from several fish, and inflammatory cytokine inhibition by IL-10 has been well examined. However, a CMI regulator of IL-10 in fish has not yet been identified. In this study, we cloned the IL-10 gene in amberjack Seriola dumerili and analyzed its function using its recombinant protein (rIL-10). In an in vitro culture experiment, gene expression of inflammatory cytokines was suppressed in leukocytes incubated with rIL-10 compared with cells that only received Nocardia seriolae stimulation. This result suggests amberjack IL-10 has conserved function as an inflammatory cytokine inhibitor. Bactericidal activity of amberjack cells against intracellular pathogen stimulation was decreased in a rIL-10 dose-dependent manner. Furthermore, a significant reduction in the T-bet/GATA-3 ratio was observed in N. seriolae living cell (LC) + rIL-10-injected fish. Taken together, these results suggest amberjack rIL-10 suppresses CMI induction both in vitro and in vivo. In addition, the number of IgM+ cells among spleen leukocytes in N. seriolae + rIL-10-injected fish was higher than in only N. seriolae LC, suggesting that Th2-dominant immunity was induced by adding rIL-10. [ABSTRACT FROM AUTHOR]