Anti-inflammatory Cytokine IL-10 Research Articles

Safety and efficacy of cellular therapy with mesenchymal stromal cells in sepsis, meta-analysis

BackgroundSepsis is a major cause of death in hospitalised patients. Dysregulated immune response is the driving pathophysiologic phenomenon underlying tissue damage and organ failure. Due to immune-modulatory properties of mesenchymal stromal cells (MSCs) several trials experimented their efficacy in sepsis. In-vitro and preclinical studies are quite promising however, clinical trials showed inconsistent results.Methods and resultsWe gathered available evidence in a meta-analysis to figure out if clinical advantage of cellular therapy in sepsis. Eleven trials were included with total of 360 patients, 191 received MSCs and 169 as control. The overall mortality was 0.248 with 95% CI 0.191–0.316. Relative to control, mortality Odds ratio (OR) was 0.54, 95% CI 0.294–1.006 and P = 0.05. Frequent MSCs infusions showed better survival, OR = 0.3, 95% CI 0.1–0.87 and P = 0.03. While survival in the cohort that received infrequent MSCs infusions was comparable with the control, OR = 0.7, 95% CI 0.35–1.41 and P = 0.3. Also, survival benefit was associated with the 1 × 106 cell/kg dose, OR = 0.31, 95% CI 0.14–0.68 and P = 0.004. While the cohort that received higher doses had OR 1.22, 95% CI 0.54–2.75 and P = 0.6. Length of hospitalisation in the MSCs cohort was significantly shorter. The standardized difference in means (d) was − 0.443, 95% CI − 0.743 to − 0.144, P = 0.004. Also, MSCs therapy was associated with significantly shorter ICU stay, d = − 0.349 with 95% CI of − 0.647 to − 0.051 and P = 0.022. Furthermore, MSCs therapy was associated with significant reduction of the proinflammatory cytokines IL-6 and IL-8 but non-significant increase of the anti-inflammatory cytokine IL-10.ConclusionCellular therapy with MSCs is a promising therapeutic modality in sepsis. Positive effects are mainly associated with frequent infusions and the dose of 1 × 106 cell/kg. Larger scale studies are needed to address the pending questions about the optimal indications and cell manipulation conditions.

Assessment of Lactobacillus acidophilus (L. acidophilus) therapeutic and prophylactic role in rats experimentally infected with Blastocystis subtype 3 (ST3).

Blastocystis, an eukaryote, inhabits the intestinal tract of humans and animals worldwide. Lactobacillus acidophilus (L. acidophilus), a probiotic, has been reported to be effective against blastocystosis. The present study evaluated the therapeutic and prophylactic effectiveness of L. acidophilus compared to metronidazole (MTZ) in rats experimentally infected with Blastocystis subtype 3 (ST3). Four groups of Blastocystis ST3-infected rats received MTZ, L. acidophilus, both MTZ and L. acidophilus, or prophylactic L. acidophilus. Non-infected and infected control groups were included. The effectiveness of treatment and prevention was evaluated using parasitological monitoring, histopathological examination, immunohistochemical staining for TNF-α and IgA expression, and immunological testing for TNF-α and IL-10. In the L. acidophilus-treated group, a 76% reduction in the mean fecal parasitic count and a 67% clearance in the intestinal wash were achieved aligning closely with outcomes observed in the MTZ-treated group. An immunomodulatory impact via upregulation of the anti-inflammatory cytokine IL-10 and downregulation of the pro-inflammatory cytokine TNF-α was demonstrated as well. Combined administration of MTZ and L. acidophilus exhibited superior efficacy with a 99% decrease in the mean fecal parasitic count and a 98% decrease in the intestinal fluid parasitic count. Additionally, the lowest TNF-α and the highest IL-10 serum levels. Prophylactic use of L. acidophilus for 7 days neither prevented infection nor reduced its severity. Furthermore, no significant differences were detected in serum levels of TNF-α and IL-10 following post-prophylaxis andpost-treatmentwith L. acidophilus. Accordingly, L. acidophilus might be recommended as an adjuvant treatment alongside MTZ for improved efficacy against blastocystosis.

P0102 Isatin: An indole alkaloid with intestinal anti-inflammatory activity in the trinitrobenzene sulfonic acid colitis model

Abstract Background Inflammatory bowel disease (IBD) is a complex and recurring inflammatory disorder that affects the gastrointestinal tract.1 Various drugs have been developed for treating IBD, but there are still limitations due to adverse effects experienced by patients.2 Plant-derived molecules with anti-inflammatory properties represent a valuable alternative as a complementary therapy for IBD.3 Isatin is a compound found in several medicinal plant species with various biological activities, including a modulatory effect on pro-inflammatory mediators. This study aimed to evaluate the effect of isatin in experimental colitis. Methods Rats were divided into three groups (10 animals/group): Saline (non-colitic control), TNBS (colitic untreated), and isatin (colitic treated with isatin 6 mg/kg). After anesthesia with ketamine (50 mg/kg) and xylazine (10 mg/kg), the TNBS and isatin groups received a single dose of TNBS (10 mg) dissolved in 0.25 mL of 50% ethanol (v/v) by rectal administration. To evaluate the intestinal anti-inflammatory activity of isatin, animals were treated 2, 24, and 48 hours after the TNBS challenge and euthanized after 72 hours by CO2 overdose. The colons were removed, the macroscopic inflammation and the colon weight/length ratio were measured and the cytokines IL-1β, IL-12, IFN-γ, and TNF-α were quantified by ELISA. Median (minimum-maximum) or mean ± SEM values were compared through the Kruskal-Wallis test (Dunn’s test) or two-way ANOVA (Tukey’s test). The experiments were approved by the Ethics Commission in Animal Use (Protocol number 2773-1). Results The TNBS group showed increased colonic wall thickness and inflammatory cell infiltration. Isatin reduced the macroscopic inflammation score [Isatin: 6 (6-7) versus TNBS: 9 (8-10); p < 0.01] promoted by TNBS instillation. Oral administration of isatin prevented the increase in the colon weight/length ratio (0.151 ± 0.017 versus 0.192 ± 0.015; p < 0.01). The colonic damage caused by TNBS instillation was also characterised by an increase in the levels of pro-inflammatory cytokines compared to the Saline group. In contrast, isatin reduced the levels of TNF-α (2.42 ± 0.72 versus 6.32 ± 1.91; p<0.001), IFN-γ (4.26 ± 1.15 versus 7.34 ± 0.48; p<0.01), IL-1β (16.54 ± 4.76 versus 35.91 ± 4.11; p<0.001), and IL-12 (13.38 ± 3.65 versus 28.87 ± 8.39; p<0.01) while increased the levels of IL-10 (6.41 ± 0.60 versus 4.82 ± 0.26; p<0.01) when compared with TNBS group. Conclusion Isatin decreased the macroscopic inflammation score and the colon weight/length ratio. The action of isatin on colitis involves the reduction of pro-inflammatory mediators such as TNF-α and IL-1β and increase of the anti-inflammatory cytokine IL-10, suggesting a potential curative role of isatin in colitis therapy.

Protective effects of hydatid cyst fluid on inflammation and tissue damage in rat model of type 1 diabetes.

Cystic echinococcosis, caused by Echinococcus granulosus, is a zoonotic disease with immunomodulatory properties attributed to hydatid cyst fluid (HCF). Given the immune-modulating and anti-inflammatory properties of HCF observed in other contexts, its potential therapeutic effects in diabetes remain unexplored. This study aimed to investigate the potential therapeutic effects of HCF on glycemic control, inflammatory cytokines, and tissue histopathology in a streptozotocin (STZ)-induced model of type 1 diabetes. Twenty male rats were randomly divided into four groups (n = 5): a healthy control group, a hydatid cyst group that received three intraperitoneal injections of HCF at two-week intervals, a diabetic group that received a single intraperitoneal dose of STZ to induce diabetes, and a hydatid cyst + diabetic group (HCF + STZ) that received both HCF treatment and STZ administration. Serum glucose levels, inflammatory cytokines (TNF-α, IL-1β, and IL-10), and histopathological changes in pancreatic and renal tissues were analyzed. The HCF + STZ group demonstrated a significant reduction in serum glucose levels compared to the STZ-only group. Pro-inflammatory cytokines TNF-α and IL-1β were significantly decreased in HCF-treated diabetic rats, while the anti-inflammatory cytokine IL-10 was partially restored. Histopathological examination revealed severe pancreatic islet atrophy and renal degeneration in the diabetic group, which were markedly alleviated in the HCF + STZ group. These findings suggest that HCF's immunomodulatory and anti-inflammatory properties may mitigate hyperglycemia and inflammatory responses in type 1 diabetes, warranting further investigation into its mechanisms and clinical applications.

A Pilot Study on the Impact of Smoking on Adipose Derived Stem Cell Function in Burn Patients.

Adipose-derived stem cells (ADSCs) have an important role in the modulation of burned tissue repair through the release of paracrine factors that stimulate the wound healing response. In this study, we tested the hypothesis that smoking status alters the profile of paracrine factors secreted from ADSCs isolated from damaged adipose tissue. Adipose tissue was collected from adult patients (N=8) with severe burn injuries (>20% total body surface area) at the index operation. ADSCs were extracted and cultured in vitro. Supernatants were harvested 30 hours after plating and used for cytokine determinations by Multiplex assay. Fluorescence activated single cell sorting (FACS) confirmed their phenotype with markers CD 90, CD 166, and CD 73. Univariate analyses were performed to compare the two cohorts (Smokers vs non smokers). Higher amounts of anti-inflammatory cytokines IL-4 (p=0.03) and IL-10 (p=0.04) and pro-inflammatory cytokines TNF-alpha (p=0.03), IL-8, and IFN-gamma (p=0.03) were detected in burn patients who were current everyday smokers when compared to nonsmokers, or former smokers. No significant differences in supernatant concentrations of IL-17, IL-1 beta, TGF-alpha, IL-6, and IL-13 were observed (p>0.05). Mortality was higher in the smoker group when compared to non-smokers. The results from this study suggest that smoking status in patients with a major burn injury may alter the paracrine factors secreted from ADSCs, and on-going studies will increase sample size and refine experimental approach. Furthermore, these results support the need for studies examining the systemic effects of smoking status of patients suffering burn injuries impacts the wound healing.

Probiotic Bacillus pumilus LV149 enhances gut repair, modulates microbiota, and alters transcriptome in DSS-induced colitis mice.

Gut microbiota dysbiosis significantly impacts ulcerative colitis (UC) progression and exacerbation. Probiotics show promise in UC management. This study evaluated the effects of different doses of Bacillus pumilus LV149, an aquatic-derived probiotic, on gut injury repair in male C57BL/6 mice with dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) and investigated the underlying mechanisms. UC was induced by allowing mice free access to a 3% DSS solution for 7 days, with concurrent daily oral gavage of either a low (LV149-L, 1 × 108 CFU/day/mouse) or high (LV149-H, 1 × 109 CFU/day/mouse) dose of LV149. The effects were assessed through physiological parameters, intestinal barrier integrity, inflammation, gut microbiota composition, and transcriptomic changes. LV149 significantly improved pathological symptoms, including weight loss and disease activity index (DAI), and reduced colon shortening in a dose-dependent manner and inflammatory damage. The intervention also restored gut barrier function by upregulating mucins, goblet cell counts, and tight junction proteins (ZO-1, occludin, and claudin-1) in colonic tissue, along with reducing serum lipopolysaccharide (LPS) levels. Notably, only the LV149-H significantly decreased the expression of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6, while both doses increased the expression of the anti-inflammatory cytokine IL-10 in a dose-dependent in colonic tissue. LV149 further modulated the gut microbiota, increasing beneficial bacteria and reducing pathogenic populations. Transcriptomic analysis indicated that LV149-L may exert gut repair effects via the IL-17 signaling pathway, whereas LV149-H appears to act through the JAK-STAT signaling pathway. This study demonstrated that LV149, particularly at a higher dose, effectively mitigated DSS-induced colonic injury by modulating gut microbiota, enhancing gut barrier integrity, and reducing inflammation. The dose-dependent effects underscored LV149-H's potential as a therapeutic agent for UC due to its stronger anti-inflammatory properties and gut-protective effects.

Chick Early Amniotic Fluid Alleviates Dextran-Sulfate-Sodium-Induced Colitis in Mice via T-Cell Receptor Pathway.

Ulcerative colitis (UC) is a chronic immune disease that is difficult to cure. We recently found that chick early amniotic fluid (ceAF) has notable anti-inflammatory and antioxidative properties, through its active components. This study demonstrates the potential of ceAF as a protective agent against UC. UPLC-MS mass spectrometry identified key components of ceAF, including various fatty acids and nucleosides. In vitro, ceAF improved viability in DSS-induced Caco-2 cells, reduced pro-inflammatory cytokines IL-1β and TNF-α, and increased the anti-inflammatory cytokine IL-10. It also upregulated the tight junction proteins ZO-1 and occludin. In DSS-induced UC mice, ceAF treatment alleviated weight loss, colon shortening, and disease activity, while improving histopathology, crypt depth, and colonic fibrosis. Mechanistically, ceAF's anti-inflammatory effects are mediated by inhibiting the overactivation of TCR signaling through the LCK/ZAP70/LAT pathway. Our findings suggest that ceAF could be a valuable nutritional intervention for UC, potentially enhancing existing functional foods aimed at managing this condition.

Intranasal exposure to commensal bacterium Rothia mucilaginosa protects against influenza A virus infection.

The respiratory tract hosts a diverse microbial community whose composition varies with anatomical location and throughout life. Rothia mucilaginosa, a common commensal of the upper respiratory tract and oral cavity, has recently been recognized for its ability to inhibit bacteria-triggered pro-inflammatory responses. However, its role in modulating the immune response to viral infections such as influenza A virus (IAV) pneumonia, remains unknown. Here, we demonstrate that R. mucilaginosa enhances protection against IAV, promoting viral clearance, reducing inflammation, preserving bronchial and alveolar structures, and improving survival in a mouse model of influenza pneumonia. The enhanced viral clearance observed in R. mucilaginosa-treated mice is associated with the recruitment of innate immune cells to the lungs, including PD-L1-expressing neutrophils, alongside the production of the anti-inflammatory cytokine IL-10, both of which are known to play regulatory roles in the context of IAV infection. Together, these findings highlight R. mucilaginosa-mediated innate immune priming as a key protective mechanism in the respiratory tract against IAV infection.

Bacillus coagulans alleviates hepatic injury caused by Klebsiella pneumoniae in rabbits.

As an opportunistic bacterial pathogen, Klebsiella pneumoniae (KP) is prone to causing a spectrum of diseases in rabbits when their immune system is compromised, which poses a threat to rabbit breeding industry. Bacillus coagulans (BC), recognized as an effective probiotic, confers a variety of benefits including anti-inflammatory and antioxidant properties. The purpose of this study was to investigate whether dietary BC can effectively alleviate hepatic injury caused by KP. In this study, the rabbits were initially pretreated with varying doses of BC (1×106, 5×106, and 1×107 CFU/g), followed by a challenge with KP at a concentration of 1011 CFU/mL. Liver tissues were harvested and processed for histological assessment using H&E and VG stains to assess structural alterations. Biochemical assays were employed to quantify the enzymatic activities of T-SOD and GSH-Px, as well as the MDA content. Furthermore, ELISA was utilized to detect the levels of inflammatory cytokine (IL-10, IL-6, IL-1β and TNF-α) and apoptotic-related gene (Bcl-2, Bax). Morphological observation indicated that BC can effectively mitigate KP-induced hepatic sinusoidal dilatation and congestion, as well as ameliorate the degree of hepatic fibrosis. Further analysis showed that BC significantly lowered MDA level in KP-treated rabbits, while enhanced the activities of T-SOD and GSH-Px. Additionally, ELISA result showed that BC pretreatment significantly reduced the levels of pro-inflammatory cytokines TNF-a, IL-6, IL-1β and pro-apoptotic gene Bax, while increasing the levels of anti-inflammatory cytokine IL-10 and anti-apoptotic gene Bcl-2 in KP-treated rabbits. Above data indicate that BC supplementation effectively attenuated oxidative stress and inflammatory response induced by KP through augmenting the activities of antioxidant enzymes and diminishing the levels of pro-inflammatory factors. Furthermore, it reduced the Bax/Bcl-2 ratio in the liver, thereby inhibiting KP-induced apoptosis. The treatment group receiving 5x106 CFU/g BC benefitted most from the protective effect.

Subacute symptoms of depression and anxiety in stress-exposed mice: Role of Schinus terebinthifolia Raddi leaf lectin (SteLL).

Anxiety and depression are leading causes of disability worldwide, often exacerbated by chronic stress. Schinus terebinthifolia Raddi. has been used in traditional medicine for several purposes. Among these, the use of bark-and-leaf tea and leaf decoction to treat depression has been reported. Previous studies showed that the S. terebinthifolia leaf lectin (SteLL) can ameliorate anxiety and depression symptoms in mice. To investigate SteLL as a compound from S. terebinthifolia leaf able to alleviate symptoms of depression and anxiety in an unpredictable chronic mild stress (UCMS) animal model. Mice were subjected to four-week UCMS and then treated with SteLL at 2 and 4mg/kg (i.p.) or with fluoxetine at 10mg/kg i.p. (positive control) for 21 days. Behavioral assessments were conducted using the open field test, elevated plus maze, tail suspension test, and sucrose preference test. Serum corticosterone and inflammatory markers (cytokines) levels were determined. The levels of cytokine, oxidative stress indicators and monoamines in brain homogenates were also measured to understand the biochemical changes induced by SteLL treatment. SteLL treatment at both doses significantly (p<0.05) alleviated the stress-induced behavior in mice, reducing the anxiety and depression signals in all tests. SteLL administration increased the brain levels of monoamines noradrenaline and serotonin in comparison with UCMS control mice that received only vehicle. SteLL reduced superoxide production, lipid peroxidation and improved reduced glutathione (GSH) levels in the brain. The lectin also increased serum and brain levels of anti-inflammatory cytokine IL-4, while reducing levels of pro-inflammatory cytokines. Serum corticosterone levels were not decreased by lectin treatment. Our findings highlight SteLL as a neuromodulatory agent from S. terebinthifolia leaves effective in subacute and stress-induced anxiety and depression through modulation of monoaminergic, oxidative stress, and inflammatory pathways. The data shows the potential of this lectin as a therapeutic agent for stress-related neuropsychological disorders.

Salmonella serovar Typhimurium infection modulates expression of immune-related genes in avian enriched monocytes

Salmonella enterica subsp. enterica serovar Typhimurium is a gram-negative bacterium that can infect various hosts. Salmonella serovar Typhimurium (ST) infection in adult poultry usually results in an asymptomatic intestinal carriage, while the infection in newly hatched chicks may lead to a severe clinical disease. Macrophages play an essential role by limiting bacterial replication in submucosal tissues using several defense mechanisms. Subsequently, Salmonella strains have developed countermeasures to evade or subvert the host immune responses to their benefit. We previously showed that the ST challenge can significantly reduce the phagocytic capacity of chicken-enriched peripheral blood monocytes. In the present study, we sought to provide a snapshot of the immune responses against ST challenge in chicken-enriched peripheral blood monocytes by evaluating the transcriptional changes in inflammatory and anti-inflammatory cytokines, pattern recognition receptors, and other immune-related molecules at the mRNA level. Our results indicate that wildtype ST challenge in avian blood monocytes favors the differentiation of macrophages toward the alternatively activated M2-like cells through downregulation of inflammatory IL-1β and upregulation of anti-inflammatory IL-10 cytokines. Our result may partially explain how the bacterium modulates the immune response in professional phagocytes to survive in the hostile environment of host immune cells and further disseminate within the host.

MARKERS OF INFLAMMATION ARE MODIFIED BY SEX, FRAILTY AND EXERCISE IN A HEAD-DOWN TILT BEDREST STUDY

Abstract Prolonged bedrest can induce physiological stress thereby exacerbating frailty and inflammation. We explored whether Head-Down Tilt (HDT) bedrest with or without exercise would alter inflammatory markers implicated in frailty. Twenty 55-65-year-old males (baseline frailty index (FI)=0.02±0.02) and females (FI=0.03±0.03) were subjected to HDT bedrest (2-weeks). Half were randomly assigned to a high-intensity interval/aerobic/strength training exercise intervention for 60 minutes/day (Control: n=4 males, 5 females; Exercise n=5 males, 6 females). FI and serum inflammatory cytokines were measured (multiplex assay) during bedrest (days 0,1,3,7,14), and recovery (days 0,4,32). Data were analyzed with linear mixed models. Proinflammatory marker levels (interleukin (IL)-6, IL-8) increased during bedrest in all groups but were higher in males than females (IL-6: ß=8.87, IL-8: ß=12.93; p&amp;lt; 0.01). IL-8 declined during recovery in all groups, although IL-8 and IL-6 remained higher in males (IL-6: ß=9.32, IL-8: ß=2.85, p&amp;lt; 0.01). The anti-inflammatory cytokine IL-10 was higher in males than females during bedrest, declined in recovery and remained highest in males. During bedrest proinflammatory cytokines (IL-1ß, IL-12) increased as frailty increased in all participants (IL- ß: ß=0.01, IL-12: ß=0.02, p&amp;lt; 0.05) whereas monocyte chemoattractant protein-1 levels declined (ß =-20.54, p&amp;lt; 0.05). The anti-inflammatory protein IL-1ra increased with frailty throughout bedrest in all, especially those who exercised (ß=3.15, p&amp;lt; 0.01). In older adults, inflammatory markers increased during bedrest, declined during recovery and were higher in males than females. Some inflammatory markers increased in parallel with frailty during bedrest. Exercise also increased IL-1ra levels, which may help reduce inflammation in older adults during prolonged bedrest.

Luteolin Exhibits Anxiolytic and Antidepressant Potential in Parkinson's Disease Rat: Antioxidant and Anti-Inflammatory Effects.

Parkinson's disease (PD) is accompanied by a complex array of nonmotor and motor manifestations. The exploration of anti-inflammatory and antioxidant active ingredient as potential therapeutic interventions in PD-associated mood alterations has gained significant attention. This study aimed to assess the antidepressant and anxiolytic properties of luteolin (LTN), a potent antioxidant and anti-inflammatory component, using a 6-hydroxydopamine (6-OHDA)-induced animal model of PD. Rats were administered LTN (10, 25, and 50 mg/kg, per oral) and fluoxetine (10 mg/kg/per oral) over a 28-day period. Behavioral tests were employed to estimate the depression- and anxiety-like behaviors. Rats treated with LTN exhibited significant improvement in 6-OHDA-induced mood alterations, as per behavioral tests. Additionally, LTN treatment led to increased hippocampal levels of catalase and superoxide dismutase, and a reduction in malondialdehyde. LTN downregulated the gene expression of nuclear factor kappa B (NF-κB)/nod-like receptor (NLR) pyrin domain-containing 3 (NLRP3) axis components, including NF-κB, NLRP3, ASC, and Caspase1 and reduced the protein level of pro-inflammatory cytokines, including interleukin (IL)-6, interleukin (IL)-1β, and tumor necrosis factor alpha (TNF-α), in addition to augmenting the protein levels of TNF-α, IL-1β, and IL-6. Furthermore, LTN exhibited an upregulatory effect on the anti-inflammatory cytokine IL-10 within the hippocampus of 6-OHDA-induced PD rats. Also, molecular docking showed higher affinity between LTN and NF-κB/NLRP3 axis components. These findings highlight the potential anxiolytic and antidepressant impacts of LTN through its antioxidant and anti-inflammatory mechanisms against 6-OHDA-induced alterations in a rat PD model.

Bacteroides fragilis capsular polysaccharide A ameliorates ulcerative colitis in rat by recovering intestinal barrier integrity and restoring gut microbiota.

Bacteroides fragilis (B. fragilis) is a Gram-negative, obligate anaerobic, commensal bacterium residing in the human gut and holds therapeutic potential for ulcerative colitis (UC). Previous studies have indicated that capsular polysaccharide A (PSA) of B. fragilis is a crucial component for its effectiveness, possessing various biological activities such as anti-inflammatory, anti-tumor, and immune-modulating effects. We previously isolated and characterized the B. fragilis strain ZY-312 from the feces of a healthy breastfed infant, and extracted its PSA, named TP2. In this study, we explored the impact of TP2 on colonic inflammation and delved into its potential mechanisms. Initially, we used 2,4,6-trinitrobenzenesulfonic acid (TNBS) to induce colitis in rats and found that TP2 treatment significantly ameliorated TNBS-induced weight loss, increased clinical scores, extensive ulcers, and intestinal epithelial damage in UC rats. Further analysis revealed that TP2 effectively restored the intestinal barrier integrity in UC rats by regulating the expression of Muc-2, tight junction proteins (ZO-1, occludin, claudin-1, and claudin-2), as well as apoptosis-related proteins Bcl-2, BAX, and Cleaved-Caspase-3. Additionally, TP2 suppressed the expression of pro-inflammatory cytokines TNF-α, IL-1β, IL-6, and IL23, while promoting the secretion of anti-inflammatory cytokines IL-10 and IL-22, thereby inhibiting the occurrence of inflammation. TP2 also downregulated the phosphorylation levels of AKT and PI3K, effectively inhibiting the abnormal activation of the PI3K/AKT signaling pathway. More interestingly, 16S rRNA sequencing results showed that TP2 restored the ecological imbalance of the rat intestinal microbiota, with an increase in beneficial bacteria such as Lactobacillus and Limosilactobacillus observed in the treatment group. In conclusion, TP2 through the regulation of intestinal barrier-related cells and proteins, inhibition of apoptosis, modulation of inflammation-related cytokine levels, and control of abnormal activation of the PI3K/AKT signaling pathway, restores intestinal barrier integrity. Additionally, by reshaping the ecological imbalance of the gut microbiota, TP2 ultimately alleviates ulcerative colitis in rats.

Heat-Killed Lactobacillus delbrueckii subsp. lactis 557 Extracts Protect Chondrocytes from Osteoarthritis Damage by Reducing Inflammation: An In Vitro Study.

Osteoarthritis (OA) is a chronic condition characterized by joint pain and disability, driven by excessive oxidative stress and inflammatory cytokine production in chondrocytes, resulting in cell death and cartilage matrix breakdown. Our previous study showed that in monosodium iodoacetate (MIA)-induced OA rats, oral administration of heat-killed Lactobacillus delbrueckii subsp. lactis 557 (LDL557) could significantly decrease OA progression. Accordingly, we designed an in vitro cell culture study aimed at investigating the effects of heat-killed LDL557 extracts on chondrocytes using SW1353 cells (a human chondrosarcoma cell line) challenged with 5 μM MIA to mimic OA conditions. The results showed that the 10 μg/mL LDL557 extracts protected SW1353 cells from MIA-induced death and reduced extracellular matrix (ECM) loss, as evaluated by toluidine blue O staining and extracellular matrix component synthesis with RT-qPCR measurement. This was achieved by decreasing the expression of MIA-induced pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α, while slightly increasing the MIA-suppressed expression of the anti-inflammatory cytokine IL-10, which were evidenced by RT-qPCR analysis. Moreover, the RT-qPCR evaluation also indicated that the LDL557 extracts slightly reduced the expression of COX-2 compared with the control, while it did not reduce the MIA-increased expression of microsomal prostaglandin E synthase-1 (mPGES-1). In addition, the LDL557 extracts influenced neither the matrix-degrading protease expressions measured via RT-qPCR nor the oxidative stress measured via fluorescence flow cytometry in the cells with or without the MIA challenge. This study demonstrates that LDL557 extracts may protect chondrocytes from OA damage by reducing inflammation-related factors and thus mitigating cartilage matrix loss, suggesting LDL557 extracts are attractive alternatives for OA applications.

Effects of ALA-PDT on the murine footpad model of Fonsecaea monophora infection and its related mechanisms in vivo.

5-aminolevulinic acid photodynamic therapy (ALA-PDT) has received growing attention for treating chromoblastomycosis (CBM) and has shown efficacy in a handful of clinical case reports. However, there is insufficient information regarding the effects of ALA-PDT on Fonsecaea monophora in mouse infection model and the related mechanisms. This study investigated these issues in vivo. A F. monophora infection mouse model inoculated in footpads was used. Changes in the footpad volume, tissue fungal burden, and histopathological characteristics were investigated to determine the efficacy of ALA-PDT. Scavenger receptor MARCO (Macrophage receptor with collagenous structure) was further evaluated at the gene and protein levels. Serum cytokines TNF-α, GM-CSF, IL-4, and IL-10 were measured using enzyme-linked immunosorbent assay to indicate changes in the immune microenvironment after PDT. ALA-PDT reduced infected footpad volume, fungal burden, and pathological inflammatory infiltration in vivo. It also increased the expression of Marco in the murine infection model. Furthermore, PDT upregulated the anti-inflammatory cytokines IL-4 and IL-10 while downregulated the pro-inflammatory cytokines TNF-α and GM-CSF in mouse serum. ALA-PDT demonstrated fungicidal effects in a mouse footpad infection model with F. monophora and attenuated the inflammatory reactions. It may also assist against the intracellular fungi by the host through macrophage receptor MARCO and regulation of the immune microenvironment. This study provides scientific evidence for the protocol selection of ALA-PDT as a promising adjunctive modality for treating chromoblastomycosis.

Transauricular vagal nerve stimulation suppresses inflammatory responses in the gut and brain in an inflammatory bowel disease model.

Inflammatory bowel disease (IBD) encompasses Crohn's disease (CD) and ulcerative colitis (UC), is a major health problem on a global scale and its treatment is unsatisfactory. We aimed to investigate the effects of transauricular vagal nerve stimulation (tVNS) on inflammation in rats with IBD induced by trinitrobenzene sulfonic acid (TNBS). A total of 36 adult female Sprague-Dawley rats were given TNBS, or vehicle, and tVNS, or sham, every other day for 30 min for 10 days. Postmortem macroscopic and microscopic colon morphology were evaluated by histological staining. Additionally, IL-1β, IL-6, IL-10, and TNF-α cytokine levels in the colon and the brain were evaluated by immunohistochemistry and western blotting analysis. TNBS induced epithelial damage, inflammation, ulceration, and thickened mucosal layer in the colonic tissues. Administration of tVNS significantly ameliorated the severity of TNBS-induced tissue damage and inflammatory response. TNBS also alters pro-inflammatory and anti-inflammatory balance in the brain tissue. TVNS application significantly suppressed the protein levels of pro-inflammatory cytokines, namely IL-1β, IL-6, and TNF- α while augmenting the level of anti-inflammatory cytokine IL-10 in the colonic and the brain tissue. We have shown that TNBS-mediated colonic inflammation and tissue damage are associated with neuroinflammatory responses in the brain tissue. Also demonstrated for the first time that neuroinflammatory response in the gut-brain axis is suppressed by tVNS in the IBD model. Non-invasive tVNS stands out as a new potential treatment option for types of IBD.

Anti-inflammatory Effects of Membrane Vesicles from Eubacterium rectale via the NLRP3 Signal Pathway.

Eubacterium rectale (E. rectale) has the ability to attenuate systemic and intestinal inflammation. Its naturally secreted membrane vesicles (MVs) likely play a crucial role in this process. The objective of this study is to investigate the anti-inflammatory effects of E. rectale and its membrane vesicles (MVs). An inflammation model was established by inducing an inflammatory response in Raw 264.7 cells using lipopolysaccharide (LPS). Subsequently, the cells were pre-treated with E. rectale and its MVs, and the expression levels of IL-1β, IL-6, TNF-α, and IL-10 in the cells were then detected using RT-qPCR. ELISA was used to measure the secretion levels of IL-1β, while western blot analysis was employed to assess the expression of key proteins in the IL-1β pathway, specifically ASC, Caspase 1, and NLRP3. The results revealed that both E. rectale and its MVs significantly reduced the expression of the inflammatory cytokines IL-1β and TNF-α in Raw 264.7 cells, which were induced by LPS. Additionally, they markedly upregulated the expression of the anti-inflammatory cytokine IL-10 and suppressed IL-1β expression via the NLRP3-Caspase 1-ASC signaling pathway. These findings suggest that E. rectale, through its membrane vesicles, can attenuate LPS-induced NLRP3 inflammasome activation, thereby mitigating the inflammatory response in Raw 264.7 cells.

Tumor Necrosis Factor Superfamily 14 Regulates the Inflammatory Response of Human Dental Pulp Stem Cells.

Dental caries is a highly prevalent chronic disease that leads to dental pulp inflammation. It is treated by removing the damaged tooth structure and applying a material that promotes resolution of pulpal inflammation. Tumor necrosis factor superfamily 14 (TNFSF14) is an immunomodulatory cytokine and a member of the TNF superfamily. This study aimed to evaluate the effect of TNFSF14 on the levels of inflammatory cytokines involved in pulpal inflammation using lipoteichoic acid (LTA)-induced human dental pulp stem cells (hDPSCs). hDPSCs were cultured and induced with LTA, followed by treatment with TNFSF14 at 25 and 50 ng/mL. Cellular viability was evaluated using the Alamar Blue assay. The levels of inflammatory cytokines IL-6, IL-8, IL-10, and TNF-α were quantified using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA). TNFSF14 at 25 and 50 ng/mL significantly reduced the mRNA and protein levels of pro-inflammatory cytokines TNF-α, IL-6, and IL-8, and increased the anti-inflammatory cytokine IL-10. In addition, TNFSF14-treated groups enhanced cell viability. Adding TNFSF14 to LTA-induced hDPSCs regulated the production of inflammatory cytokines by lowering the levels of IL-6, IL-8, and TNF-α and elevating IL-10 levels.

Intraperitoneal Treatment of Cambinol, a Synthetic SIRT1 and SIRT2 Inhibitory Compound, Exacerbates Brucella abortus 544 Burden in the Spleens of Institute of Cancer Research Mice.

Our preliminary data using bone marrow-derived macrophages (BMDMs) collected from ICR mice treated with anti-sirtuin (anti-SIRT) 1 antibody showed that Brucella uptake was significantly attenuated. We then further investigated the effect of an inhibitor of SIRT1/2, cambinol, in the progression of Brucella. The in vitro results using RAW264.7 cells revealed that cambinol treatment had no effect on adhesion, uptake, intracellular survival and nitric oxide (NO) production during B. abortus infection, nor did it directly affect bacterial growth for up to 72 h. Finally, intraperitoneal treatment of 8-week-old female ICR mice infected with Brucella showed no differences in the total average weights of spleens and livers; however, the treated mice displayed higher Brucella colony-forming units (CFUs) from the spleens. Furthermore, the interleukin (IL)-10 serum level was observed to be lower in treated mice at 7 d post-infection, and none of the cytokines tested showed a change at 14 d post-infection. The overall findings showed that cambinol treatment had no effect on the proliferation of Brucella in RAW264.7 macrophages but exacerbated the splenic proliferation of the bacteria in mice and displayed reduced anti-inflammatory cytokine IL-10 at the first week of infection, suggesting that cambinol as an inhibitory of SIRT1/2 could be beneficial in the context of Brucella dissemination in animal hosts and that exploration of activating SIRTs could be an alternative treatment against Brucella infection.