Search Results (20,866)

Although mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) are as effective as MSCs in the suppression of allergic airway inflammation, few studies have evaluated the immunomodulatory capacity of MSC-derived EVs in patients with asthma. Thus, we assessed the effects of adipose stem cell (ASC)-derived EVs on cytokine expression and regulatory T cells (Tregs) in peripheral blood mononuclear cells (PBMCs) of asthmatic patients. PBMCs (1 × 10⁶ cells/mL) were isolated from asthmatic patient and healthy controls and co-cultured with 1 μg/mL of ASC-derived EVs. Th (T helper) 1-, Th2-, and Treg-related cytokine expression, fluorescence-activated cell sorting analysis of CD4⁺CD25⁺FOXP3⁺ T cells, and co-stimulatory molecules were analyzed before and after ASC-derived EV treatment. The expression levels of IL-4 and costimulatory molecules such as CD83 and CD86 were significantly higher in PBMCs of asthmatic patients than in control PBMCs. However, ASC-derived EV treatment significantly decreased the levels of interleukin (IL)-4 and co-stimulatory molecules such as CD83 and CD86 in the phytohemagglutinin (PHA)-stimulated PBMC of asthmatic patients. Furthermore, ASC-derived EVs remarkably increased the transforming growth factor-β (TGF-β) levels and expression of Tregs in the PBMC of asthmatic patients. ASC-derived EVs induce Treg expansion and have immunomodulatory effects by downregulating IL-4 and upregulating TGF-β in PBMCs of asthmatic patients. Full article

Background: The diverse clinical characteristics of erosive esophagitis (EE) and symptom perception in patients with gastroesophageal reflux disease (GERD) remain a major challenge in understanding their underlying pathogenesis. This study aimed to investigate the association between the levels of IL-8, TNF-α, and IL-17 in serum and the presence of erosive esophagitis and symptoms related to GERD. Method: We enrolled 65 subjects presenting with GERD symptoms. Based on the findings of upper endoscopy, the subjects were categorized into two groups: (1) erosive esophagitis (EE LA grades B-D) and (2) non-erosive esophagitis (normal-EE LA grade A). Symptom perception was assessed via GERD questionnaire (GERD-Q) and the frequency scale for the symptoms of GERD (FSSG). The enzyme-linked immunosorbent assay (ELISA) method was used to analyze serum levels of IL-8, TNF-α, and IL-17. Analysis of cytokine levels between different symptoms severity was performed using the Kruskal-Wallis H test. Results: Median serum IL-8 levels were significantly higher in the erosive esophagitis group compared to those with non-erosive esophagitis (20.2 (IQR 16.9–32.2) vs. 17.7 (IQR 15.2–19.6), p < 0.05). The study found a significant association between IL-8 levels and the presence of globus symptoms (median IL8 level 46.961 (38.622–92.644) in subjects with globus vs. 18.06 (16.68–20.49) in those without globus; p < 0.05). Similarly, TNF-α levels were associated with the frequency of regurgitation symptoms (H index = 10.748; dr = 3; p < 0.05). We observed a significant correlation between IL-17 levels and the frequency of heartburn and early satiety symptoms. Conclusions: IL-8 may play a role in the development of mucosal erosion in GERD. IL-8, TNF- α, and IL-17 might be involved in the development of globus symptoms, the frequency of regurgitation, and the frequency of heartburn and early satiety, respectively. The diverse symptom phenotypes observed in patients with GERD symptoms may be mediated by distinct profiles of proinflammatory cytokines. Full article

Ischemic stroke (IS) is a critical medical condition that results in significant neurological deficits and tissue damage, affecting millions worldwide. Currently, there is a significant lack of reliable tools for assessing and predicting IS outcomes. The inflammatory response following IS may exacerbate tissue injury or provide neuroprotection. This review sought to summarize current knowledge on the IL-1 family’s involvement in IS, which includes pro-inflammatory molecules, such as IL-1α, IL-1β, IL-18, and IL-36, as well as anti-inflammatory molecules, like IL-1Ra, IL-33, IL-36A, IL-37, and IL-38. The balance between these opposing inflammatory processes may serve as a biomarker for determining patient outcomes and recovery paths. Treatments targeting these cytokines or their receptors show promise, but more comprehensive research is essential to clarify their precise roles in IS development and progression. Full article

Despite significant advances in prenatal medicine, spontaneous miscarriage remains one of the most common and serious pregnancy complications, affecting an increasing number of women. Since many aspects of the pathogenesis of spontaneous miscarriage remain unexplained, the aim of this study has been to assess the involvement of the NLRP3 inflammasome as a potential causative factor. The concentrations of NLRP3, IL-1β, IL-18, and cytochrome C in the serum of patients after miscarriage were measured by means of the immunoenzymatic method. In the placental tissue, the expression of NLRP3, IL-1β, IL-18, and Caspase-1 as well as that of the classical apoptosis biomarkers Fas, FasL, Bcl-2, and Ca was evaluated by means of immunohistochemistry techniques. Additionally, in whole blood, the concentrations of elements crucial for pregnancy progression, such as Ca, K, Mg, and Na, were examined by means of the ICP-OES method. Significantly higher concentrations of NLRP3 and IL-18 were demonstrated in the serum of patients with miscarriage as compared to the control group. In the placental tissue samples, a higher expression of IL-1β, IL-18, and Caspase-1 proteins was noted in women who had experienced miscarriage as compared to the control group. At the same time, a significantly lower expression of FasL and Bcl-2 proteins as well as Ca deposits was observed in women after miscarriage as compared to those with a normal pregnancy outcome. Significantly lower concentrations of Ca and K were recorded in the blood of patients with spontaneous miscarriage as compared to pregnant women. The analysis of the results x indicated a greater involvement of the inflammasome in women with spontaneous miscarriage associated with oxidative–antioxidative imbalance than in the case of miscarriage related to NET formation. Our research has provided evidence for the involvement of the inflammasome in the process of spontaneous miscarriage and identifies a new direction for diagnostics that includes NLRP3 as a preventive element in prenatal care, particularly in light of the steadily declining number of pregnancies and the increasing number of reproductive failures. Full article

Dendrobium officinale flowers (DOF) have previously been established as a promising source of natural antioxidants, and it is ideally suited for processing to prepare functional foods and food additives. The precise extraction processes employed, however, can alter the composition and antioxidant properties of the resultant products, and the characteristic compounds associated with the active fractions prepared from DOF or their mechanisms of action have yet to be reported. To clarify the molecular mechanisms through which these active fractions function for the first time, chromatography was used to separate DOF extracts, yielding five fractions (Fr. (a—e)). Analyses of the antioxidant activity for these different fractions revealed that Fr. (d) presented with the most robust bioactivity. Levels of total flavonoids were then measured, revealing that antioxidant activity levels were positively correlated with total flavonoid content. Fr. (d) was found to contain 20 flavonoids in HPLC-Triple-TOF-MS/MS analyses. At the cellular level, Fr. (d) was found to induce increases in the levels of protective antioxidant factors (SOD and GSH-Px) while reducing the levels of reactive oxygen species (ROS), damage-associated factors (MDA, NO, TNF-α, IL-1β, and IL-6), and inducible nitric oxide synthase (iNOS) expression in C2C12 cells that had been stimulated with H₂O₂. These data thus provided support for Fr. (d) prevention of oxidative stress and inflammation. Network pharmacology analyses further suggested that Fr. (d) can help protect against oxidative stress through its effects on PI3K/Akt-related signaling activity. Fr. (d) was subsequently found to upregulate PI3K/Akt pathway-related proteins, nuclear transcription factor 2 (Nrf2), and heme oxygenase 1 (HO-1) in addition to suppressing Kelch-like epoxide-related protein 1 (Keap1) expression. In summary, Fr. (d) was found to suppress PI3K/Akt/Nrf2 pathway activation, ultimately alleviating inflammation and oxidative stress as predicted with a network pharmacology approach. Future studies aimed at clarifying the composition and mechanistic activity of DOF Fr. (d) will likely help establish it as a functional food capable of promoting health and longevity. Full article

Klebsiella pneumoniae (K. pneumoniae), a kind of zoonotic bacteria, is among the most common antibiotic-resistant pathogens, and it causes nosocomial infections that pose a threat to public health. In this study, the roles of synthetic bovine neutrophil β-defensin-5 (B5) in regulating inflammatory response and metabolic response against multidrug-resistant K. pneumoniae infection in a mouse model were investigated. Mice were administrated intranasally with 20 μg of B5 twice and challenged with K. pneumoniae three days after B5 pretreatment. Results showed that B5 failed to directly kill K. pneumoniae in vitro, but it provided effective protection against multidrug-resistant K. pneumoniae via decreasing the bacterial load in the lungs and spleen, and by alleviating K. pneumoniae-induced histopathological damage in the lungs. Furthermore, B5 significantly enhanced the mRNA expression of TNF-α, IL-1β, Cxcl1, Cxcl5, Ccl17, and Ccl22 and obviously enhanced the rapid recruitment of macrophages and dendritic cells in the lungs in the early infection phase, but significantly down-regulated the levels of TNF-α, IL-1β, and IL-17 in the lungs in the later infection phase. Moreover, RNA-seq results showed that K. pneumoniae infection activated signaling pathways related to natural killer cell-mediated cytotoxicity, IL-17 signaling pathway, inflammatory response, apoptosis, and necroptosis in the lungs, while B5 inhibited these signaling pathways. Additionally, K. pneumoniae challenge led to the suppression of glycerophospholipid metabolism, the phosphotransferase system, the activation of microbial metabolism in diverse environments, and metabolic pathways in the lungs. However, B5 significantly reversed these metabolic responses. Collectively, B5 can effectively regulate the inflammatory response caused by K. pneumoniae and offer protection against K. pneumoniae. B5 may be applied as an adjuvant to the existing antimicrobial therapy to control multidrug-resistant K. pneumoniae infection. Our study highlights the potential of B5 in enhancing pulmonary bacterial clearance and alleviating K. pneumoniae-caused inflammatory damage. Full article

This study aimed to assess the impact of pre-competition training by comparing the differences of collegiate sprinters in physiological state between strengthening and tapering training period by sportomics and combining their sport performance. Fifteen collegiate sprinters were investigated or tested on their body composition, dietary habits, energy expenditure, sleep efficiency, heart rate and respiratory rate during training, blood (blood cells, biochemical and immune markers) and urine (urinalysis), gut microbiome distribution, microbiome and blood metabolites, and their functions during the strengthening (Group A) and tapering training period (Group B) prior to competing in the national competitions. We found that 26.67% of sprinters achieved personal bests (PB) after the competition. The limb skeletal muscle mass and lymphocyte ratio of male sprinters in Group B were lower than those in Group A, and the serum creatine kinase (CK) level was higher than Group A (p < 0.05). The levels of serum CK, interleukin-6 (IL-6), interleukin-1β (IL-1β), and urine-specific gravity (SG) of the two groups were higher than the upper limit of the reference value. The detection rates of urine white blood cell (WBC) and protein in Group B were higher than those in Group A. The gut microbiome health index (GMHI) of Group A was higher than that of Group B, and the microbial dysbiosis index was lower than that of Group B. The ratio of Firmicutes/Bacteroidota (F/B) in Group A was higher than that in Group B. There were 65 differential metabolites in the A/B group, and the enriched pathway was mainly the NF-kappa B signaling pathway (up); B/T cell receptor signaling pathway (up); Th1 and Th2 cell differentiation (up); phenylalanine metabolism (up); and growth hormone synthesis, secretion, and action (up). There were significant differences in blood metabolites between the A and B groups, with a total of 89 differential metabolites, and the enriched pathway was mainly the NF-kappa B signaling pathway (up), T cell receptor signaling pathway (up), Th1 and Th2 cell differentiation (up), and glycerophospholipid metabolism (down). In conclusion, the imbalance of the gut microbiome and inflammation and immune-related metabolites of collegiate sprinters during the pre-competition tapering training period may be the cause of their limited sports performance. Full article

Coronary aneurysms are typically defined as sections of a coronary artery where the diameter is more than 1.5 times that of an adjacent normal segment. In rare circumstances, these aneurysms can become exceedingly large, leading to the classification of giant coronary artery aneurysms. Despite their occurrence, there is no clear consensus on the precise definition of giant coronary artery aneurysms, and their etiology remains somewhat ambiguous. Numerous potential causes have been suggested, with atherosclerosis being the most prevalent in adults, accounting for up to 50% of cases. In pediatric populations, Kawasaki disease and Takayasu arteritis are the primary causes. Although often discovered incidentally, coronary artery aneurysms can lead to severe complications. These complications include local thrombosis, distal embolization, rupture, and vasospasm, which can result in ischemia, heart failure, and arrhythmias. The optimal approach to medical, interventional, or surgical management of these aneurysms is still under debate and requires further clarification. This literature review aims to consolidate current knowledge regarding coronary artery aneurysms’ pathophysiology, emphasizing their definition, causes, complications, and treatment strategies. Recent research has begun to explore the molecular mechanisms involved in the formation and progression of coronary artery aneurysms. Various molecules, such as matrix metalloproteinases (MMPs), inflammatory cytokines, and growth factors, play crucial roles in the degradation of the extracellular matrix and the remodeling of vascular walls. Elevated levels of MMPs, particularly MMP-9, have been associated with the weakening of the arterial wall, contributing to aneurysm development. Inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukins (IL-1β and IL-6) have been implicated in promoting inflammatory responses that further degrade vascular integrity. Additionally, growth factors such as vascular endothelial growth factor (VEGF) may influence angiogenesis and vascular remodeling processes. Understanding these molecular pathways is essential for developing targeted therapies aimed at preventing the progression of coronary artery aneurysms and improving patient outcomes. Full article

Vitamin D₃ transporter (DBP) is a multifunctional protein. Site-specific deglycosylation results in its conversion to group-specific component protein-derived macrophage activating factor (GcMAF), which is capable of activating macrophages. It has been shown that depending on precursor conversion conditions, the resulting GcMAF activates mouse peritoneal macrophages towards synthesis of either pro- (IL-1β, TNF-α—M1 phenotype) or anti-inflammatory (TGF-β, IL-10—M2 phenotype) cytokines. The condition for the transition of the direction of the inflammatory response of macrophages when exposed to GcMAF is the initial glycosylated state of the population of DBP molecules and the associated effective deglycosylation of DBP by β-galactosidase. In vivo experiments with GcMAF exhibiting anti-inflammatory properties on models of induced arthritis in mice and cystitis in rats indicate a significant anti-inflammatory effect of the macrophage activator. The feasibility of unidirectional induction of anti-inflammatory properties of macrophages allows creation of combined therapeutic platforms where M2 macrophages are among the key therapeutic components. Full article

Localized scleroderma (LS) is an autoimmune disease characterized by inflammation and fibrosis, leading to severe cutaneous manifestations such as skin hardening, tightness, discoloration, and other textural changes that may result in disability. While LS shares similar histopathologic features and immune-fibroblast interactions with systemic sclerosis (SSc), its molecular mechanisms remain understudied. Endothelial cells (EC) are known to play a crucial role in SSc but have not been investigated in LS. Single-cell RNA sequencing (scRNA-seq) now allows for detailed examination of this cell type in the primary organ of interest for scleroderma, the skin. In this study, we analyzed skin-isolated cells from 27 LS patients (pediatric and adult) and 17 healthy controls using scRNA-seq. Given the known role of EC damage as an initial event in SSc and the histologic and clinical skin similarities to LS, we focused primarily on endothelial cells. Our analysis identified eight endothelial subclusters within the dataset, encompassing both disease and healthy samples. Interaction analysis revealed that signaling from diseased endothelial cells was predicted to promote fibrosis through SELE interaction with FGFBP1 and other target genes. We also observed high levels of JAG in arterial endothelial cells and NOTCH in capillary endothelial cells, indicating the activation of a signaling pathway potentially responsible for epidermal abnormalities and contributing to LS pathogenesis. In summary, our scRNA-seq analysis identified potential disease-propagating endothelial cell clusters with upregulated pathways in LS skin, highlighting their importance in disease progression. Full article

Biological drugs, including monoclonal antibodies, represent a revolutionary strategy in all fields of medicine, offering promising results even in the treatment of osteoarthritis (OA). However, their safety and efficacy have not been fully validated, highlighting the need for in-depth studies. Therefore, we provided a comprehensive systematic review of the intra-articular use of monoclonal antibodies for the treatment of OA in animal models, reflecting ongoing efforts to advance therapeutic strategies and improve patient outcomes. A systematic literature search was conducted in December 2023 following the PRISMA guidelines, using the Web of Science, Google Scholar, and PUBMED databases. Out of a total of 456, 10 articles were included in the study analyzing intra-articular antibodies and focusing on various targets, including vascular endothelial growth factor (VEGF), nerve growth factor (NGF), interleukin 4-10 (IL4-10), tumor necrosis factor α (TNF-α), a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5), and matrix metalloproteinase 13 (MMP-13). Most studies administered the antibodies weekly, ranging from 1 to 10 injections. Animal models varied, with mean follow-up periods of 8.9 ± 4.1 weeks. The methods of assessing outcomes, including pain and morpho-functional changes, varied. Some studies reported only morphological and immunohistochemical data, while others included a quantitative analysis of protein expression. In conclusion, monoclonal antibodies represent a promising avenue in the treatment of OA, offering targeted approaches to modulate disease pathways. Further research and clinical trials are needed to validate their safety and efficacy, with the potential to revolutionize the management of OA and reduce reliance on prosthetic interventions. Full article

Objective: Prostate tumors, if prostate cancer or adenoma, represent a major public health challenge. Progress in research on inflammation has revealed a connection between inflammation, immunity, and cancer. In this context, this study aimed to find IL-6 signaling systemic abnormalities in the inflammatory tumor microenvironment. Material and methods: This study was case–controlled, multicentered, and included 86 patients, 43 diagnosed with BPH and 43 diagnosed with PCa, between January 2019 and January 2020. The study group was homogenous and the studied parameters were IL-6 complex (IL-6, soluble receptor IL-6R, soluble glycoprotein gp130), acute phase proteins (C reactive protein—CRP, acid alpha1 glycoprotein—AGPA, ferritin, albumin, transferrin), and oxidative stress-associated variables (malondialdehyde—MDA, carbonylated protein—PCO, 8-hydroxy-deoxy guanosine-8-OHdG, total antioxidant status—bTAS). Results: The inflammatory microenvironment determined IL-6 signaling alterations (over-regulation of sIL-6R and suppression of sgp130 in PCa versus BPH), changes in acute phase reaction markers (increased serum levels of CRP, AGPA, ferritin, and decreased serum levels of albumin, transferrin) that were much more evident in PCa compared to BPH, an imbalance between macromolecular oxidative damage (MDA, PCO, 8-OHdG) and endogenous antioxidants (TAS) that was more accentuated in PCa compared with BPH, and a representative association between the sIL-6R/sgp130 ratio and inflammatory/oxidative stress-related factors only in PCa patients. Conclusions: Our study reconfirms the anterior concept that IL-6 promotes prostatic tumorigenesis. In this study, we first demonstrated that a high sIL-6R/sgp130 ratio facilitates prostate malignancy. Full article

Objective: Milk production during lactation places a high demand for calcium that is fulfilled both from maternal bone resorption and diet. While it is known that mammary gland-derived PTHrP drives bone resorption during lactation, the impact of postpartum estrogen loss on bone has been unclear. Methods: We used a case-control study design to test the effect of estrogen loss in lactating mice. Results: In the present study, we show for the first time that estrogen loss during lactation activates memory T-cells (T_M) to produce TNFα and IL-17A to aid in bone resorption and calcium release. Our studies reveal a new mechanism for the release of calcium from bone postpartum. The findings provide several new insights. First, the immune system plays a critical role in milk production postpartum. Second, evolutionarily, the pathway serves the physiological purpose of increasing bone resorption to release calcium for breastmilk production postpartum but becomes maladaptive postmenopause, leading to osteoporosis. Finally, these results highlight the crosstalk between the brain–bone–breast–endocrine axis and the immune system during lactation. Full article

Background: Previous studies of the hydroethanolic extract of Virola elongata inner stem bark (HEVe) have demonstrated its antioxidant, gastroprotective, and antiulcer properties, but have not evaluated its anti-inflammatory potential. Methods: HEVe was obtained by maceration and phytochemically analyzed. Its systemic anti-inflammatory activity was assessed by its effect on lipopolysaccharide (LPS)-induced peritonitis in mice. HEVe gel (HEgVe) was employed to evaluate topical anti-inflammatory activity by measuring the ear edema resulting from croton-oil-induced dermatitis in mice. A cell viability assay was conducted to determine the non-cytotoxic concentrations of the HEVe. RAW 264.7 cells were stimulated by LPS to determinate cytokine and nitric oxide production. Results: A phytochemical analysis of the HEVe revealed the presence of phenolic acids, neolignans, flavonoids, and monomeric catechins. The oral treatment of acute peritonitis with HEVe reduced the total leukocytes, neutrophils, TNF-α, and IL-1β and elevated IL-10 levels. The application of the HEgVe reduced local edema. The HEVe on the RAW 264.7 cells exhibited no cytotoxicity, and the cells with HEVe displayed reduced TNF-α, IL-1β, and NO levels and increased IL-13 levels. Conclusions: HEVe demonstrated systemic and topical multitarget anti-inflammatory activity, likely due to the combined effects of secondary metabolites. HEVe emerges as a promising herbal remedy for inflammation with minimal cytotoxicity, emphasizing its potential therapeutic significance. Full article

The synthetic peptide TAT-I24 (GRKKRRQRRRPPQCLAFYACFC) exerts antiviral activity against several double-stranded (ds) DNA viruses, including herpes simplex viruses, cytomegalovirus, some adenoviruses, vaccinia virus and SV40 polyomavirus. In the present study, in vitro profiling of this peptide was performed with the aim of characterizing and improving its properties for further development. As TAT-I24 contains three free cysteine residues, a potential disadvantageous feature, peptide variants with replacements or deletions of specific residues were generated and tested in various cell systems and by biochemical analyses. Some cysteine replacements had no impact on the antiviral activity, such as the deletion of cysteine 14, which also showed improved biochemical properties, while the cyclization of cysteines 14 and 20 had the most detrimental effect on antiviral activity. At concentrations below 20 µM, TAT-I24 and selected variants did not induce hemolysis in red blood cells (RBCs) nor modulated lipopolysaccharide (LPS)-induced release of cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), in human peripheral blood mononuclear cells (PBMCs). These data indicate that TAT-I24 or its peptide variants are not expected to cause unwanted effects on blood cells. Full article