IL-17A Levels Research Articles

Dexamethasone-loaded fibroin nanoparticles promote retinal reattachment in rats by regulating the Th17/Treg balance

Retinal detachment (RD) is a common acute blinding eye disease, and dexamethasone (DEX), an adrenocorticosteroid, shows protective effects against RD. However, its poor water solubility and low bioavailability limit its effectiveness. To address this, we developed SF@DEX nanomaterials and investigated their therapeutic potential and mechanisms in RD. The nanomaterials were successfully synthesized and characterized, achieving 90% encapsulation efficiency and releasing 60% of DEX within 12 h.In vitro, phagocytosis was measured by flow cytometry, and enzyme-linked immunosorbent assay determined interleukin-17 (IL-17) and interleukin-10 (IL-10) levels. A rat RD model was established surgically, followed by oral administration of silk fibroin (SF), SF@DEX, and DEX. Polymerase chain reaction (PCR) assessed IL-17A and forkhead box P3 (FOXP3) expression, while Western blot analysed transforming growth factor-β1 (TGF-β1), IL-10, IL-17A, and FOXP3 levels. Apoptosis of retinal ganglion cells was evaluated using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, and confocal microscopy detected colocalization of IL-17A and FOXP3. SF@DEX treatment significantly reduced Th17 cells and IL-17A while increasing Tregs, FOXP3, TGF-β1, and IL-10 levels. The severity of RD in rats was notably alleviated by SF@DEX, demonstrating its anti-inflammatory effects through modulation of the Th17/Treg immune balance. These results highlight SF@DEX as a promising nano-based therapy for RD.

Changes in tear cytokine and lactoferrin levels in postmenopausal women with primary acquired nasolacrimal duct obstruction complicated with obstructed meibomian gland dysfunction

BackgroundEpiphora and secondary ocular surface damage are increasingly impairing the quality of life of people, particularly elderly women. We aimed to investigate the changes in tear cytokine and lactoferrin levels in postmenopausal women with primary acquired nasolacrimal duct obstruction (PANDO) complicated with obstructed meibomian gland dysfunction (OMGD) and preliminary explore the pathological mechanisms of OMGD in patients with PANDO.MethodsThe prospective study involved 43 and 41 postmenopausal women with and without PANDO, respectively. Based on the presence or absence of OMGD, the participants were subdivided. Tear fluid was collected from affected eyes of all participants using Schirmer I test and tested for cytokine concentrations (interleukin (IL)-6, IL-8, IL-1β, interferon-gamma, tumour necrotic factor (TNF)-α, IL-10, epidermal growth factor (EGF)) using the Multiplex Luminex Assay. Tear lactoferrin levels was determined using ELISA.ResultsIn the PANDO with OMGD group, the IL-8, IL-1α, IL-1β, and macrophage inflammatory protein-1α levels were significantly higher than those in the other groups. The IL-6 and TNF-α levels were significantly higher than those in the controls. The lactoferrin level in the PANDO with OMGD group was lower than that in the Non-PANDO with OMGD group. The IL-10 and EGF levels were not significantly different among the groups.ConclusionThe level of pro-inflammatory factors in the tears of patients with PANDO complicated with OMGD was significantly increased, which is likely to cause further damage to ocular surface. Anti-inflammatory therapy may help protect ocular surface in postmenopausal women with PANDO.

IL-17 family members exert an autocrine pro-inflammatory loop in CF respiratory epithelial cells ex vivo.

Lungs of people with Cystic Fibrosis (pwCF) are characterized by chronic inflammation and infection with P. aeruginosa. High levels of IL-17A and F have been observed in sputum of pwCF and the interleukin-17(IL-17) family (A-to-F) has been suggested to play a key role in CF pulmonary disease. We measured mRNA levels of IL-17 receptors (IL-17R) by RT-qPCR in CF bronchial epithelial (CFBE) cultured cells upon infection with P. aeruginosa PAO1 strain or clinical exoproducts (EXO) isolated from pwCF. We measured IL-17 mRNA expression by RT-qPCR and the release of cytokines by ELISA and Bioplex from CF primary nasal epithelial (HNE) cultured cells. Infection of CFBE cells with PAO1 or EXO isolated from 15 pwCF significantly increased mRNA expression of all IL-17R, except IL-17RD. Infection of HNE cells with EXO isolated from the correspondent donor significantly increased the mRNA levels of all the IL-17 cytokines and receptors, except for IL-17D and IL-17RD, and the release of the cytokines IL-17A, IL-17B, IL-17C, IL-17E and IL-17F. HNE exposed to IL-17A and F were induced to release pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), neutrophil chemokines (IL-8, G-CSF) and cytokines known to be involved in chloride and bicarbonate secretion, together with mucin upregulation (IL-4, IL-13). These results highlight a wider expression of IL-17 family member in respiratory epithelial cells, which can play a role as an autocrine inflammatory amplification loop in CF airways. These in-vitro studies using patient-derived cultures underline the relevant role of IL-17 family members in CF pulmonary immune response.

Jiawei Yanghe Decoction alleviates pulmonary sarcoidosis by upregulating NR1D1/2 and suppressing Th17 cells.

Jiawei Yanghe Decoction (JWYHD) is a modified version traditional Chinese medicine formula Yanghe Decoction which has been used to treat various autoimmune diseases. However, the effect of JWYHD on pulmonary sarcoidosis remains unclear. This study aimed to determine the therapeutic efficacy and potential mechanism of action of JWYHD in pulmonary sarcoidosis. A murine model of sarcoidosis was established by intravenous injection of inactivated Propionibacterium acnes and mature dendritic cells to assess the efficacy of JWYHD. Lung tissue mRNA sequencing was conducted to identify the targets of JWYHD's action. Molecular docking verified of the interaction between identified compounds and key targets. JWYHD treatment alleviated the formation of granulomas in the lung tissue of sarcoidosis model mice. JWYHD significantly attenuated the pulmonary accumulation of macrophages and CD4+T lymphocytes in sarcoidosis mice, and effectively suppressed the proportion of Th17 cells and the levels of IL-17A and TNF-α in BALF, which are pivotal in the pathogenesis of granuloma formation and progression. The therapeutic efficacy of JWYHD was found to be equivalent to that of prednisone. RNA-seq revealed that JWYHD upregulated Nr1d1/2 expression in the lung tissue. Nr1d1/2 is highly expressed in Th17 cells and regulates their differentiation. The NR1D1/2 agonist SR9009 could inhibit Th17 cell proportion and reduce the formation of pulmonary granuloma, exhibiting effects similar to those of JWYHD. Molecular docking result showed that Cyclocephaloside II, Epimedin B, Glycyrrhetic acid, Glycyrrhizic acid, Uralsaponin B, and Uralsaponin U may be key compounds in JWYHD for the treatment of pulmonary sarcoidosis, which had a strong binding ability for NR1D1/2. JWYHD might exert a therapeutic benefit in pulmonary sarcoidosis through upregulating NR1D1/2 and suppressing Th17 cells. NR1D1/2 might serve as a therapeutic target for the treatment of pulmonary sarcoidosis.

Probiotic administration aggravates dextran sulfate sodium salt-induced inflammation and intestinal epithelium disruption in weaned pig

BackgroundA. muciniphila (AKK) has attracted extensive research interest as a potential next-generation probiotics, but its role in intestinal pathology is remains unclear. Herein, this study was conducted to investigate the effects of A. muciniphila DSM 22,959 on growth performance, intestinal barrier function, microecology and inflammatory response of weaned piglets stimulated by dextran sulfate sodium salt (DSS).MethodTwenty-four Duroc × Landrace × Yorkshire (DLY) weaned piglets used for a 2 × 2 factorial arrangement of treatments were divided into four groups with six piglets in each group. From 1 to 15 d, the CA and DA groups were orally fed with 1.0 × 1011 colony-forming units A. muciniphila per day, while the CON and DCON groups were received gastric infusion of anaerobic sterile saline per day. The pigs were orally challenged (DCON, DA) or not (CON, CA) with DSS from day 9 to the end of the experiment and slaughtered on day 16.ResultsPresence of A. muciniphila in DSS-challenged weaned pigs resulted in numerically increased diarrhea rate, blood neutrophilic granulocyte, serum C-reactive protein and immunoglobulin M levels, and numerically reduced final weight, average daily feed intake and average daily gain. The decrease in intestinal villus height, villous height: crypt depth ratio and digestibility was accompanied by lower expression of ZO1, ZO2, Claudin1, DMT1, CAT1, SGLT1 and PBD114 genes, as well as decreased enzyme activities of intestinal alkaline phosphatase, lactase, sucrase and maltase of piglets in DA group compared to piglets in DCON group. The abundance of Bifdobacterium, Lactobacillus, A. muciniphila, Ruminococcus gnavus was numerically higher in digesta of pigs in DA group than those in DCON group. The inflammatory responses of piglets were dramatically changed by the simultaneous presence of A. muciniphila and DSS: expression level of IL17A, IL17F, IL23, RORγt, Stat3 was elevated in DA pigs compared to the other pig groups.ConclusionsOur result showed that the oral A. muciniphila aggravates DSS-induced health damage of weaned piglet, which may attribute to the deteriorating intestinal morphology, dysbiosis of microbiota and inflammatory response disorders.

Association of anti-phosphatidylserine/prothrombin antibodies with adverse in vitro fertilization outcomes.

Anti-phosphatidylserine/prothrombin antibodies (aPS/PT) are classified as non-criteria antiphospholipid antibodies (aPL), and are strongly associated with thrombosis and pregnancy complications linked to antiphospholipid syndrome (APS). This study aimed to investigate whether aPS/PT positivity is associated with adverse outcomes in vitro fertilization (IVF). The study included infertile women who tested positive aPS/PT and underwent IVF cycles, as well as infertile controls with pure tubal etiology. We compared the impact of aPS/PT on baseline and clinical characteristics, immune-related indicators, IVF laboratory metrics, and pregnancy outcomes. Women with aPS/PT exhibited lower numbers of retrieved oocytes, embryos, and both perfect and available embryos, as well as reduced rates of blastocyst formation. Furthermore, an imbalanced Th17/Treg ratio and significantly elevated serum IL-17A levels were observed in women with aPS/PT compared to controls. In conclusion, the presence of aPS/PT is associated with adverse IVF and pregnancy outcomes. Early screening for aPS/PT and appropriate consultation for couples undergoing IVF-ET should be considered. Additionally, specific immune and inflammatory mechanisms related to aPS/PT warrant further investigation.

The relationship of irisin, apelin-13, and immunological markers il-1α & amp, il-1β with diabetes in kidney failure patients.

Chronic kidney disease (CKD) is often complicated by diabetes, impacting various biochemical and immunological markers. This study aimed to investigate the relationship between irisin, apelin-13, and immunological markers IL-1α and IL-1β in diabetic patients with CKD. This cross-sectional study was conducted from January to June 2023 in a tertiary care hospital in Tikrit City, Iraq. This study included 120 CKD patients and a control group including 20 healthy individuals. Patients were included in the study by convenience sampling method. Participants were evaluated using ELISA kits for irisin, apelin-13, and cytokines, with blood samples analyzed for relevant biochemical markers. Patients had irisin levels of 10.98 ± 2.5 ng/mL, significantly different from non-diabetic patients (12.40 ± 3.54 ng/mL) and controls (5.36 ± 1.06 ng/mL) (p<0.001). Apelin-13 was higher in diabetic patients (537.71 ± 124.78 pg/mL) compared to controls (181.26 ± 29.98 pg/mL) (p<0.001). IL-1α levels in diabetic patients were 715.30 ± 392.48 pg/mL, significantly higher than in control patients (206.27 ± 26.49 pg/mL) (p<0.001). IL-1β levels were 351.50 ± 81.82 pg/mL in diabetics, also higher than in control (145.79 ± 38.49 pg/mL) (p<0.001). The study highlights significant associations between biochemical markers and CKD in diabetic patients. Elevated levels of irisin, apelin-13, IL-1α, and IL-1β may serve as potential biomarkers for diabetes-related CKD complications.

The investigation of peripheral inflammatory and oxidative stress biomarkers in dementia with Lewy Bodies, compared with Alzheimer's Disease, and mild cognitive impairment.

Although inflammation and oxidative stress have been increasingly recognised as components of Alzheimer's disease (AD) and Parkinson's disease (PD) pathologies. Few studies have investigated peripheral inflammation, and none have examined oxidative stress in Dementia with Lewy bodies (DLB). The purpose of our study was to characterize and compare those biomarkers in DLB with those in AD and amnestic mild cognitive impairment (aMCI). Plasma samples were obtained from Chinese patients with DLB (n = 50), AD (n = 59), and aMCI (n = 30), and healthy controls (HCs) (n = 54). Peripheral inflammatory biomarkers, including interferon-gamma (IFN-γ), interleukins (IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12p70, IL-17A), tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP). Oxidative stress markers, such as superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px), were also assessed. The findings revealed that DLB patients had higher IL-6 levels than AD and HCs and elevated IL-10 and IL-17A levels compared to HCs. In terms of oxidative stress, the levels of SOD were significantly lower and MDA were significantly higher in the DLB and AD compared with HCs. Significant positive correlations were found between Unified Parkinson's Disease Rating Scale (UPDRS) scores and CRP levels. Our study identifies a unique peripheral immune and oxidative stress profile in DLB, characterized by elevated IL-6, MDA, and reduced SOD levels, distinguishing it from AD. These findings, linked to α-synuclein (α-Syn) pathology, provide novel insights into DLB mechanisms and highlight potential biomarkers for disease monitoring, targeted therapies, and future clinical trials.

The Effect of T-Cell Transcription Factors on the Immunopathogenesis of Rheumatoid Arthritis

Objective: This looks at investigates the impact of T-cell transcription factors at the immunopathogenesis of rheumatoid arthritis (RA). Methods: An overall of 60 sufferers diagnosed with RA and handled in our health center between January 2022 and January 2024 had been selected because the remark organization, whilst 60 healthy those who underwent routine health test-usual through the equal length had been distinct as the manipulate group. Peripheral blood samples from each organization were analyzed to measure the proportion and proliferative interest of regulatory T cells (Tregs), as well as their inhibitory feature on effector T cells. Levels of the T-cell transcription component STAT3 and associated inflammatory factors were additionally tested. RA patients had been handled with a STAT3 inhibitor to take a look at changes in Treg proliferation, inhibitory function, and the secretion stages of seasoned-inflammatory factors. Additionally, synovial tissue from RA patients changed into received for histopathological evaluation the usage of mild microscopy to assess synovial infection and hyperplasia. Results: The peripheral blood of the remark organization confirmed substantially decrease Treg counts compared to the manipulate group (P &lt; 0.05). The in vitro proliferation charge of Tregs in the remark group was additionally decrease than within the manipulate group (P &lt; 0.05). Levels of p-STAT3, TNF-α, IFN-γ, and IL-17A in Tregs have been higher within the commentary group, and the expression tiers of TNF-α, IFN-γ, and IL-17A mRNA have been also improved in comparison to the manage group (P &lt; 0.05). RA sufferers handled with 50 μg/L STAT3 inhibitor confirmed a substantially better Tresp suppression price in comparison to untreated sufferers (P &lt; 0.05). However, there has been no statistically tremendous distinction in Treg proliferation charges among the treated institution and the control institution (P &gt; 0.05). The expression of p-STAT3 protein in Tregs became lower in the treated group compared to untreated sufferers (P &lt; 0.05), and not using a big difference as compared to the manage organization (P &gt; 0.05). Similarly, TNF-α, IFN-γ, and IL-17A mRNA stages had been reduced in the dealt with organization compared to untreated sufferers (P &lt; 0.05), but no great distinction turned into found whilst in comparison to the manage group (P &gt; 0.05). Histopathological evaluation discovered mentioned inflammatory responses in the synovial tissue of the statement organization, inclusive of congestion and edema of the synovial stroma, full-size lymphocyte and plasma cellular infiltration, focal necrosis, epithelial hyperplasia, fibrinous exudation, and necrotic particles accumulation. Conclusion: RA patients show off synovial inflammation and hyperplasia, together with a lack of ability to efficiently suppress Tresp cells thru Tregs. The mechanism is intently related to peculiar STAT3 expression. Inhibiting aberrant STAT3 expression extensively influences the immunopathogenesis of RA, probably restoring Treg feature, assuaging seasoned-inflammatory thing secretion, and preventing the development of RA.

Baicalin ameliorates neuroinflammation by targeting TLR4/MD2 complex on microglia via PI3K/AKT/NF-κB signaling pathway.

This study aims to elucidate the target and mechanism of baicalin, a clinically utilized drug, in the treatment of neuroinflammatory diseases. Neuroinflammation, characterized by the activation of glial cells and the release of various pro-inflammatory cytokines, plays a critical role in the pathogenesis of various diseases, including spinal cord injury (SCI). The remission of such diseases is significantly dependent on the improvement of inflammatory microenvironment. Toll-like receptor 4/myeloid differentiation protein 2 (TLR4/MD2) complex plays an important role in pathogen recognition and innate immune activation. baicalin, a natural flavonoid, is renowned for its potent anti-inflammatory property. In this study, we discovered that baicalin significantly reduced the activation of glial cells and the levels of pro-inflammatory cytokines at the lesion site of SCI mice, thereby mitigating demyelination and neuronal damage. By directly occupying the active pocket of TLR4/MD2 complex on microglia, baicalin inhibited PI3K/AKT/NF-κB pathway, thereby exerting its anti-inflammatory effect. These findings were corroborated in mice induced by lipopolysaccharide, a TLR4 agonist. Furthermore, baicalin indirectly altered phenotype of astrocytes by reducing secretion of TNF-α, IL-1α, and C1q levels from microglia. Our work demonstrated that baicalin effectively alleviated neuroinflammation by directly targeting microglia and indirectly modulating astrocytes phenotype. As a natural flavonoid, baicalin holds significant potential as a therapeutic candidate for diseases characterized by neuroinflammation.

The PPAR-α selective agonist WY14643 improves lupus nephritis via the downregulation of the RORγT/STAT3 signaling pathway in MRL/lpr mice.

Systemic lupus erythematosus (SLE) is a classic autoimmune disorder that mostly affects young women and involves various organs, such as the skin, joints, central nervous system, and kidneys. WY14643, a selective agonist of peroxisome proliferator-activated receptor-α, has previously shown anti-inflammatory effects in various disease models. However, its effects on lupus nephritis are yet to be explored. Therefore, the efficacy of WY14643 on renal biomarkers and lupus nephritis was assessed in MRL/lpr mice. Flow cytometry was used to examinethe effects of WY14643 on the expression of IL-17A, STAT3, RORγT, IL-21, IL-21R, IL-22, and TNF-α in splenic CD4+ T cells. We further investigated the impact of WY14643 on the mRNA expression of IL-17A, STAT3, RORγT, IL-21, IL-21R, IL-22, and TNF-α in kidney tissue via RT-PCR analysis. The administration of WY14643 effectively improved the symptoms of lupus nephritis in MRL/lpr mice. The administration of WY14643 decreased serum albumin, urine protein, serum creatinine, and blood urea nitrogen levels in MRL/lpr mice. WY14643 reduced the levels of inflammatory markers, including CD4+IL-17A+, CD4+STAT3+, CD4+RORγT+, CD4+IL-21+, CD4+IL-21R+, CD4+IL-22+, and CD4+TNF-α+, in the spleen cells of MRL/lpr mice. Additionally, we discovered that the administration of WY14643 resulted in the suppression of mRNA levels of IL-17A, STAT3, RORγT, IL-21, IL-22, and TNF-α. The current work shows that the suppression of inflammatory cells by WY14643 may effectively reduce autoimmune characteristics, such as renal inflammation, in lupus-prone MRL/lpr mice. Therefore, WY14643, being a specific PPAR-α agonist, shows significant potential as a novel therapeutic option for treatingnephritis associated with SLE, offering hope for future treatments in this challenging field.

Inhibition of Th17 cell differentiation by aerobic exercise improves vasodilatation in diabetic mice

ABSTRACT Background Aortic endothelial diastolic dysfunction is an early complication of diabetes and the abnormal differentiation of Th17 cells is involved in the development of diabetes. However, the exact role of exercise on regulating the Th17 cells differentiation and the underlying molecular mechanisms remain to be elucidated in diabetic mice. Methods db/db and db/m+ mice were randomly divided into exercise and sedentary groups. Mice in exercise group were exercised daily, 6 days/week, for 6 weeks and mice in sedentary groups were placed on a nonmoving treadmill for 6 weeks. Vascular endothelial function was measured via wire myograph and the frequencies of Th17 from peripheral blood in mice were assessed via flow cytometry. Results Our data showed that exercise improved insulin resistance and aortic endothelial diastolic function in db/db mice. In addition, the proportion of Th17 cells and IL-17A level in peripheral blood of db/db mice were significantly increased, and exercise could promote Th17 cell differentiation and reduce IL-17A level. More importantly, STAT3 or ROR-γt inhibitors could promote Th17 cell differentiation in db/db mice, while exercise significantly down-regulated p-STAT3/ROR-γt signaling in db/db mice, suggesting that exercise regulated Th17 differentiation through STAT3/ROR-γt signaling. Conclusions This study demonstrated that exercise improved vascular endothelial function in diabetic mice via reducing Th17 cell differentiation through p-STAT3/ROR-γt pathway, suggesting exercise may be an important non-pharmacological intervention strategy for the treatment of diabetes-related vascular complications.

AP-1 activates KCNN4-mediated Ca2+ signaling to induce the Th1/Th17 differentiation of CD4+ cells in chronic non-bacterial prostatitis

The intraprostatic inflammatory infiltrate is characterized by Th1 CD4+ T cells, and its molecular mechanism is not well defined. This study explored the mechanisms responsible for the alteration of Th1/Th17 differentiation of CD4+ T cells in chronic non-bacterial prostatitis (CNP). CNP rats were induced by the administration of testosterone and 17β-estradiol. The Th1/Th17 cell percentage was increased in the prostate tissue of CNP rats, which was accompanied by increased IL-2, IFN-γ, IL-17A, and IL-22 levels. Transcriptome sequencing was performed, followed by KEGG pathway enrichment analysis. Activator protein-1 (AP-1) was enhanced in CD4+ T cells from CNP rats, and its inhibitor SR11302 suppressed Th1/Th17 differentiation and delayed CNP. AP-1 transcriptionally activated the expression of KCNN4, which potentiated mTORC1 in CD4+ T cells by enhancing Ca2+ signaling, thereby promoting Th1/Th17 differentiation. Rapamycin-mediated autophagy activation reversed AP-1/KCNN4/mTORC1-promoted Th1/Th17 differentiation, thereby inhibiting CNP. These results suggest that AP-1-mediated KCNN4 transcription promotes the inhibition of autophagy by mTORC1 through Ca2+ signaling, which supports Th1/Th17 differentiation of CD4+ T cells, resulting in the transformation of CNP to prostatic intraepithelial neoplasia and adenocarcinoma.

Secreted extracellular heat shock protein gp96 and inflammatory cytokines are markers of severe malaria outcome.

Malaria caused by Plasmodium spp., is a major public health issue in sub-Saharan Africa. The fight against malaria has stalled due to increasing resistance to treatments and insecticides. There is an urgent need to focus on new therapeutic targets to combat malaria effectively. This study aimed to measure the secreted heat shock protein gp96 levels in both malaria patients and controls. Indeed, gp96 plays a crucial role in parasite survival within the host and in establishing a successful infection. Therefore, gp96 could be a promising target for antimalarial drugs. In our study, we included 60 malaria patients, 30 with Severe Malaria (SM) and 30 with Uncomplicated Malaria (UM). Additionally, 28 controls (CTR) were included. Using the ELISA method We measured gp96 levels in the participants' blood samples. We then used the Mann-Whitney or ANOVA tests to calculate descriptive statistics and determined the correlation between gp96 level and parasitemia using Spearman's rank correlation test. The study found that gp96 levels in the plasma significantly increased in malaria patients (23.86ng/mL) compared to control (5.88ng/mL), with a p < 0.0001. Interestingly, there was a significant difference between SM (27.56ng/mL) and UM (13.9ng/mL), with a p-value of 0.001. These findings are accompanied by significantly higher parasitemia and elevated proinflammatory cytokines such as IL-17A and IL-1β levels in SM patients compared to UM and controls. Furthermore, there was no significant positive correlation between gp96 levels and parasitemia/proinflammatory cytokines. Our research has revealed, for the first time, that individuals with severe malaria have significantly higher levels of gp96 in the context of high parasitemia and proinflammatory cytokines. Our preliminary results will be taken further to evaluate gp96 as a valuable biomarker for the diagnosis of severe malaria and a potential target for antimalarial drug discovery.

Compartmentalization of the Inflammatory Response in the Pericardial Cavity in Patients Undergoing Cardiac Surgery.

The systemic inflammatory response after cardiopulmonary bypass has been widely studied. However, there is a paucity of studies that focus on the local inflammatory changes that occur in the pericardial cavity. The purpose of this study is to assess the inflammatory mediators in the pericardial fluid of patients undergoing cardiac surgery. We conducted a prospective cohort study on patients undergoing aortic valve replacement. Pericardial fluid and peripheral venous blood samples were collected after the opening of the pericardium. Additional samples were obtained from peripheral blood and the pericardial fluid shed through mediastinal drains 24 and 48 h after surgery. Levels of interleukin 1α (IL-1α), interleukin 1β (IL-1β), interleukin 2 (IL-2), interleukin 4 (IL-4), interleukin 6 (IL-6), interleukin 8 (IL-8), interleukin 10 (IL-10), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), vascular endothelial growth factor (VEGF), monocyte chemotactic protein-1 (MCP-1), epidermal growth factor (EGF), soluble E-selectin, L-selectin, P-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) were determined in all pericardial fluid and serum samples. A total of 45 patients with a mean age of 74 years were included, of which 66% were males. Serum levels of IL-6, IL-8, and MCP-1 were significantly increased at 24 and 48 h after surgery. No significant changes were observed in the serum levels of the remaining mediators. A significant increase of postoperative pericardial fluid levels of IL-1α, IL-1β, IL-6, IL-8, IL-10, IFN-γ, VEGF, MCP-1, VCAM-1, and P-selectin was observed at 24 and 48 h after surgery. There is a robust systemic and pericardial inflammatory response after cardiac surgery on cardiopulmonary bypass. However, postoperative pericardial inflammatory activity shows a distinct pattern and is more marked than at the systemic level. These findings suggest that there is a compartmentalization of the inflammatory response within the pericardial cavity after cardiac surgery.

Anticancer effect of a combinatorial treatment of 5-fluorouracil and cell extract of some probiotic lactobacilli strains isolated from camel milk on colorectal cancer cells.

Colorectal cancer (CRC) has the highest mortality rate among cancer types, emphasizing the need for auxiliaries to 5-fluorouracil (5-FU) due to resistance and side effects. Metabolites produced by probiotic bacteria exhibit promising anticancer properties against CRC. In the current study, the anticancer effects of cell extract of three potential probiotic lactobacilli strains isolated from camel milk, Lactobacillus helveticus, Lactobacillus gallinarum, and Lactiplantibacillus plantarum, as well as that of the standard probiotic strain Lacticaseibacillus rhamnosus GG (LGG), on the human colon cancer cell line (HT-29) and the normal HEK293 cell line separately or in combination with 5-FU, were evaluated. This study isolated strains from camel milk and compared their probiotic properties to those of LGG. The cell viability, cell apoptosis, and Th17 cytokine production were assessed using the MTT assay, acridine orange/ethidium bromide (AO/EB) staining, and flow cytometry techniques, respectively. The cell extracts of lactobacilli strains combined with 5-FU reduced HT-29 cell viability effectively and increased cell apoptosis. Nevertheless, the cell extracts of lactobacilli strains combined with 5-FU controlled the cytotoxic impact of 5-FU on HEK-293 cell viability and reduced cell apoptosis. No significant differences were observed among the strains. Moreover, the cell extracts from the strains combined with 5-FU increased the levels of cytokines IFN-γ, TNF-α, and IL-17A, all of which contribute to immunity against tumors. The performance of the studied strains was similar to that of the standard probiotic strain (LGG). The investigation revealed that cell extracts from lactobacilli strains may serve as a promising complementary anticancer treatment.

Repetitive Overuse Injury Causes Entheseal Damage and Palmar Muscle Fibrosis in Older Rats.

Overuse injury is a frequent diagnosis in occupational medicine and athletics. Using an established model of upper extremity overuse, we sought to characterize changes occurring in the forepaws and forelimbs of mature female rats (14-18 months of age). Thirty-three rats underwent a 4-week shaping period, before performing a high-repetition low-force (HRLF) task for 12 weeks, with the results being compared to 32 mature controls. HRLF animals showed a reduced grip strength versus controls. ELISAs carried out in the HRLF rats, versus controls, showed elevated levels of IL1-α in tendons, IL1-α and TNF-α in distal bones/entheses, and TNF-α, MIP1-α/CCL3, and CINC-2/CXCL-3 in serum, as well as IL-6 in forelimb muscles and tendons, and IL-10 in serum. HRLF rats had elevated collagen deposition in the forepaw intrinsic muscles (i.e., fibrosis), entheseal microdamage, and articular cartilage degradation versus the control rats. CD68/ED1+ osteoclasts and single-nucleated cells were elevated in distal forelimb metaphyses of the HRLF animals, versus controls. Declines in grip strength correlated with muscle fibrosis, entheseal microdamage, articular cartilage damage, distal bone/enthesis IL1-α, and serum IL-6. These data demonstrate inflammatory and persistent degradative changes in the forearm/forepaw tissues of mature female animals exposed to prolonged repetitive tasks, changes with clinical relevance to work-related overuse injuries in mature human females.

Assessment of Interleukin-17A and Interleukin-2 Serum Levels in Patients with Alopecia Areata

Background: Alopecia areata (AA) is a condition that leads to the loss of hair in the part of the body due to the destruction of hair follicles, and causing patchy, non-scarring hair loss. The source of AA is unclear; however, there is much evidence assuming that alopecia areata is a disease mediated by the immune system. Aim: To measure the levels of serum interleukin (IL-17A and IL-2) in alopecia areata patients and their associations with the severity and period of illness, along with other prognostic disease variables. Materials and Methods: To perform the study, 40 patients with alopecia areata and 40 healthy controls were registered. The serum levels of IL-2 and IL-17A in alopecia areata patients and healthy controls were evaluated by applying ELISA techniques (Sandwich ELISA). Results: Compared to the healthy group, patients with alopecia areata revealed much higher levels of IL-17A and IL-2 (p &gt; 0.05). Baseline interleukin levels did not associate statistically significantly with the severity or period of the disease. Conclusions: The current study suggests that IL-17A and IL-2 were strongly linked with alopecia areata and may have a crucial role in the condition's progress.

Prevalence of fungal colonization among patients with psoriasis in difficult-to-treat areas: impact of apremilast on mycotic burden and clinical outcomes

IntroductionFungi, including Candida, may be a trigger or exacerbate psoriasis, especially in difficult to treat (DTT) areas, through the activation of IL-17/23 axis.MethodsIn this study, seventy patients with DDT psoriasis were enrolled to evaluate Candida species and/or other opportunistic fungi colonization rate at baseline (T0) and the impact of apremilast on fungal load, clinical outcome, serum cytokine levels and biochemical serum profile of patients after 16, 24 and 52 weeks of treatment.ResultsIn our population, 33 (47%) patients were colonized by Candida spp. at baseline. In 24 (34%) individuals Candida was detected in the oral cavity while in the remaining 9 (13%) individuals the fungus was isolated from stool samples. Twenty subjects were colonized by only the species C. albicans, whereas in the remaining 13 a combination of two or more species (C. albicans plus non-albicans strains) was found in the oral cavity. Moreover, 27 (39%) patients were affected by onychomycosis. At 52 weeks, apremilast treatment induced a full recovery from Candida colonization in 83% of patients colonized with a single species of Candida (C. albicans); while in those co-infected by two or more Candida spp. induced a significant reduction (colony counts &amp;gt;10 CFU/mL) in fungal load was observed in comparison to baseline. Among patients with onychomycosis, 78% (21/27) of them presented a complete clinical resolution of nail psoriasis and concomitant nail infections. Finally, improvements in clinical scores i.e., PASI, NAPSI, DLQI, itch VAS, PAIN VAS, scPGA and sPGA-G and biochemical serum profile, as well as a significant decrease in serum IL-17A, TGF-β 1 and IL-10 levels (from 8.51 to 4.16 pg/mL; from 66.10 to 48.70 ng/mL and from 20.05 to 14 pg/mL, respectively) were observed in all patients.ConclusionsFungi may play a role in the psoriasis pathogenesis. Apremilast has been shown to ameliorate psoriasis signs and symptoms and counteract fungal overgrowth, probably by dampening inflammation, triggered by the fungal infections themselves. Thus, apremilast may represent an effective therapeutic approach in the treatment of DTT psoriasis and modulate the fungal colonization.

Quercetin alleviates ulcerative colitis through inhibiting CXCL8-CXCR1/2 axis: a network and transcriptome analysis

IntroductionUlcerative colitis (UC) is a chronic inflammatory condition of the intestinal tract in which mucosal healing is a crucial measure of therapeutic efficacy. Quercetin, a flavonoid prevalent in various foods and traditional Chinese medicines, exhibits notable pharmacological properties, including antioxidant and anti-inflammatory activities. Consequently, it warrants investigation to determine its potential therapeutic effects on UC. The objective of this study was to investigate the effects and underlying mechanisms of quercetin in a murine model of UC.MethodsA comprehensive approach integrating network predictions with transcriptomic analyses was employed to identify the potential targets and enriched pathways associated with quercetin in UC. Subsequently, the effects of quercetin on pathological morphology, inflammatory mediators, and mucosal barrier-associated proteins, as well as the identified potential targets and enriched pathways, were systematically investigated in a murine model of dextran sulfate sodium (DSS)-induced UC.ResultsNetwork analyses identified CXCL8 and its receptors, CXCR1 and CXCR2, as primary target genes for therapeutic intervention in UC. Further validation through transcriptomic analysis and immunofluorescence staining demonstrated significant upregulation of the CXCL8-CXCR1/2 axis in the intestinal tissues of patients with UC. Experimental investigations in animal models have shown that quercetin markedly alleviates DSS-induced symptoms in mice. This effect includes the restoration of colonic crypt architecture, normalization of goblet cell structure and density, reduction of inflammatory cell infiltration, and decreased concentrations of inflammatory mediators. Quercetin enhanced the expression of tight junction (TJ) proteins, including ZO-1, MUC2 (Mucin 2), and occludin, thereby preserving the integrity of the intestinal mucosal barrier. Additionally, it significantly diminished the levels of IL-17A, NF-κB, CXCL8, CXCR1, and CXCR2 in the colonic tissues of mice with UC.DiscussionThe ameliorative effects of quercetin on colon tissue damage in DSS-induced UC mice were significant, possibly due to its ability to inhibit the CXCL8-CXCR1/2 signaling axis. These findings provide a solid foundation for the clinical application and pharmaceutical advancement of quercetin.