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Permanent inflammatory demyelinating and neurodegenerative processes lead to neurological disability in patients with multiple sclerosis (MS). The anti-inflammatory properties of vitamin D3 (VitD) are well established, but its role in neurodegeneration is still uncertain. The usefulness of the serum concentration of VitD as a potential biomarker in evaluating brain injury in terms of recently known smoldering MS was under consideration. Methods: We assessed the concentrations of the parameters of brain injury (NF-H, GPAF, S100B, UCHL1) in the cerebrospinal fluid (CSF) of relapsing-remitting (RRMS, n = 123) and progressive MS (PMS, n = 88) patients in the group with normal levels of VitD (VitDn) and in the VitD deficiency group (VitDd). The levels of NF-H and UCHL1 were higher in the group of VitDd compared to VitDn. The higher serum levels of VitD were correlated with lower concentrations of GFAP, NF-H and S100B in the CSF of the whole group of MS patients and in women with MS as opposed to the levels of UCHL1. In men, there were noted negative correlations between the levels of serum VitD and GFAP and NF-H in CSF but not between VitD and S100B and UCHL1. The negative correlations were observed between VitD and the selected parameters of brain injury in MS patients, in women as well as in men. The concentrations of serum VitD together with selected parameters of brain injury in CSF seem to be promising biomarkers of neurodegeneration processes in smoldering MS. [ABSTRACT FROM AUTHOR]

Background: Inflammatory demyelination and impaired recovery processes result in permanent neurodegeneration and neurological disability in patients with multiple sclerosis (MS). In terms of smoldering MS, chronic neuroinflammation develops in the early period of the disease and leads to confirmed disability accumulation. There is a great need to identify biomarkers of neurodegeneration and disease progression. Methods: A single-center prospective observational study was performed. The median age of the patients was 40 (31–52) years. Women comprised 64% of the study population. We evaluated the concentrations of the parameters of brain injury (NF-H, GFAP, S100B and UCHL1) in the cerebrospinal fluid (CSF) and the selected interleukins (ILs) in serum of 123 relapsing–remitting MS (RRMS) and 88 progressive MS (PMS) patients. Results: The levels of GFAP, S100B and UCHL were higher in the PMS group than the RRMS group, in contrast to the levels of NF-H. We observed a positive correlation between the selected pro-inflammatory cytokines and the parameters of brain injury. The Expanded Disability Status Scale (EDSS) score increased with GFAP and NF-H levels and was correlated with the selected ILs. The concentrations of S100B, UCHL1 and NF-H reflected the duration of MS symptoms. Conclusions: The levels of brain injury parameters in the CSF and the selected serum ILs in MS patients seem to be promising biomarkers to determine neurodegeneration and neuroinflammation in smoldering MS. Further studies are warranted in this respect. [ABSTRACT FROM AUTHOR]

Dentofacial inflammation resulting from untreated dental caries is a serious disease that can spread to deeper tissues of the neck and face. This study aimed to analyze salivary cytokine profiles as potential biomarkers of acute odontogenic infections in children. The study group consisted of 28 children aged 3–17 years old with acute dentofacial infections (DI) and a control group (caries experience, CE) of 52 children aged 4–17 years old with uncomplicated dental caries. The cytokine profile was analyzed using the Bio-Plex Pro Human Cytokine 27-Plex kit in the saliva of children in both groups. The levels of IL-4, IL-15, FGF-2, G-CSF, and PDGF-BB were significantly increased in children with dentofacial infections compared to the control group. In contrast, the levels of other cytokines, such as IL-2, IL-7, IL-9, IL-13, GM-CSF, and IFN-γ, did not show statistically significant differences between these two groups. IL-4, IL-15, FGF-2, G-CSF, and PDGF-BB may serve as potential selective biomarkers of inflammation of the oral cavity in children. These biomarkers can be useful in identifying and monitoring the progress and treatment of bacterial infections resulting in dentofacial inflammation. [ABSTRACT FROM AUTHOR]

Cytokines regulate immune responses and are crucial to MS pathogenesis. This study evaluated pro-inflammatory and anti-inflammatory cytokine concentrations in the CSF of de novo diagnosed RRMS patients compared to healthy controls. We assessed cytokine levels in the CSF of 118 de novo diagnosed RRMS patients and 112 controls, analyzing relationships with time from symptom onset to diagnosis, MRI lesions, and serum vitamin D levels. Elevated levels of IL-2, IL-4, IL-6, IL-13, FGF-basic, and GM-CSF, and lower levels of IL-1β, IL-1RA, IL-5, IL-7, IL-9, IL-10, IL-12p70, IL-15, G-CSF, PDGF-bb, and VEGF were observed in RRMS patients compared to controls. IL-2, IL-4, IL-12p70, PDGF, G-CSF, GM-CSF, and FGF-basic levels increased over time, while IL-10 decreased. IL-1β, IL-1RA, IL-6, TNF-α, and PDGF-bb levels negatively correlated with serum vitamin D. TNF-α levels positively correlated with post-contrast-enhancing brain lesions. IL-15 levels negatively correlated with T2 and Gd(+) lesions in C-spine MRI, while TNF-α, PDGF-bb, and FGF-basic correlated positively with T2 lesions in C-spine MRI. IL-6 levels positively correlated with post-contrast-enhancing lesions in Th-spine MRI. Distinct cytokine profiles in the CSF of de novo diagnosed MS patients provide insights into MS pathogenesis and guide immunomodulatory therapy strategies. [ABSTRACT FROM AUTHOR]

(1) Background: Studies indicate that vitamin D (VitD) may reduce inflammation in multiple sclerosis (MS). The aim of the study was to assess the effect of supplementation with different doses of VitD on inflammation in relapsing-remitting MS (RRMS) patients. (2) Methods: The effect of 6-month supplementation with different doses of oral VitD (2000 IU/day) in a high-dose group (HD, n = 23) and a low-dose group (15,960 IU/month) (LD, n = 29) on selected markers of inflammation was assessed in 52 RRMS patients. (3) Results: Females constituted the majority of participants (63.46%). The median age [years] was 39.5 [34.5–49.8] and 47 [40.0–55.0] in the HD and LD groups, respectively. Significant differences were observed in age (p = 0.028), body weight (p = 0.014) and height (p = 0.001) between the study groups. Considering the BMI, statistically significant differences were not found (p = 0.496). The median 25(OH)D concentration [ng/mL] increased from 23.023 [15.578–25.76] in the HD group and 28.318 [20.644–32.232] in the LD group to 29.819 [24.937–38.064] and 30.837 [25.382–36.789], respectively (p < 0.01), and the increase was significantly higher in the HD group (p = 0.01). Hypovitaminosis D was found in most patients (71.2%) initially, and serum VitD levels were still <30.0 ng/mL in 46.2% of the participants at the follow-up. A significant increase in the levels of IL-4, IL-6, IL-17A, IL-22, IL-23 and TNF -α [pg/mL] and a decrease in IL-10 levels were reported during the study (p < 0.01). A significant positive correlation was observed between 25(OH)D serum levels and sCD40L (R = 0.33; p < 0.05) and TNF-α (R = 0.28; p < 0.05), and a significant negative correlation was reported between 25(OH)D and IL-23 (R = −0.32; p < 0.01) at the beginning of the study. (4) Conclusions: In RRMS patients, the doses of VitD were probably too low to induce beneficial effects on inflammation. Further studies are warranted to determine the effect of VitD supplementation on inflammatory markers in MS patients. [ABSTRACT FROM AUTHOR]

A novel research objective is to identify new molecules in more readily accessible biological fluids that could be used in the diagnosis of multiple sclerosis (MS) and other demyelinating disorders. To compare the level of selected cytokines in tears between patients with MS or other demyelinating disorder and healthy controls. 84 patients with diagnosed MS during remission or with other demyelinating disease of the CNS and 70 healthy controls were enrolled in the study. Tears were collected without any stimulation and stored till the day of assessment. The concentration of selected cytokines was measured by the Bio-Plex Pro Human cytokine screening panel 27 cytokines assay according to the manufacturer's instructions. Statistical analysis was performed with Statistica 13. IL-1b level was significantly lower in the study group compared to the control group [3,6 vs 8.71, p < 0.001]. The same pattern was observed for IL-6 [3,1 vs 5.26, p = 0.027] and IL-10 [1,7 vs 10.92, p < 0.001] (Table 1). In the study group, IL-1RA (p = 0.015), IL-5 (p = 0.04), IL-9 (p = 0.014), and IL-15 (p = 0.037) showed significant correlations with age. In the total sample, IL-1Ra (p = 0.016) and IFN-g (p = 0.041) were significantly correlated with age, while in the control group, IL-8 (p = 0.09), MIP-1a (p = 0.009), and RANTES (p = 0.031) showed significant correlations. Our results show that MS and other demyelination diseases lead to decrease in the overall level of cytokines in tears. Further research is needed to determine the role of tear fluid in the assessment of demyelinating disorders like MS. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease. Patients with relapsing–remitting MS (RRMS) and secondary progressive MS (SPMS) differ in their responses to treatment; therefore, the correct diagnosis of the particular type of MS is crucial, and biomarkers that can differentiate between the forms of MS need to be identified. The aim of this study was to compare the levels of inflammatory parameters in serum samples from patients with RRMS and SPMS. The study group consisted of 60 patients with diagnosed MS. The patients were divided into RRMS and SPMS groups. In the RRMS patients, the usage of disease-modifying treatment was included in our analysis. The serum levels of inflammatory parameters were evaluated. The serum levels of BAFF, gp130 and osteopontin were significantly higher in SPMS patients than in RRMS patients. The serum levels of BAFF correlated with age in both RRMS and SPMS patients. The serum levels of MMP-2 were significantly higher in RRMS patients than in SPMS patients and correlated with the number of past relapses. The serum levels of IL-32 were significantly higher in RRMS treatment-naïve patients than in RRMS patients treated with disease-modifying therapy. Significant differences were found in BAFF, gp130, MMP-2 and osteopontin levels between RRMS and SPMS patients. Serum IL-32 levels were statistically lower in RRMS patients treated with disease-modifying therapy than in treatment-naïve patients. [ABSTRACT FROM AUTHOR]

The burden of cardiovascular disease and the percentage of frail patients in the aging population will increase. This study aims to assess the circulating levels of several cytokines in frail patients. This is an ancillary analysis of the FRAPICA trial. The ratio of men/women changed from robust through frail groups from 3:1 to 1:2. The groups are comparable in terms of age and body measurements analysis (weight, height, and BMI), yet the frail patients have significantly reduced fat-free mass, and more often have been diagnosed with diabetes. Frail patients have higher fibroblast growth factor basic (FGF basic) and follistatin levels (borderline significance). In multiple linear regression modeling of fat-free mass, we identified FGF basic, osteopontin, stem cell factor, soluble suppression of tumorigenicity 2, soluble epidermal growth factor receptor, soluble human epidermal growth factor receptor 2, follistatin, prolactin, soluble interleukin 6 receptor alfa, platelet endothelial cell adhesion molecule 1, soluble vascular endothelial cell growth factor receptor 1, leptin, soluble angiopoietin/tyrosine kinase 2, and granulocyte colony-stimulating factor. We have identified a few cytokines that correlate with fat-free mass, a hallmark of frailty. They comprise the kinins implicated in bone and muscle metabolism, fibrosis, vascular wall function, inflammation, endocrine function, or regulation of bone marrow integrity. [ABSTRACT FROM AUTHOR]

The inflammatory process is triggered by several factors such as toxins, pathogens, and damaged cells, promoting inflammation in various systems, including the cardiovascular system, leading to heart failure. The link between periodontitis as a chronic inflammatory disease and cardiovascular disease is confirmed. Propolis and its major component, caffeic acid phenethyl ester (CAPE), exhibit protective mechanisms and anti-inflammatory effects on the cardiovascular system. The objective of the conducted study was to assess the anti-inflammatory effects of the Polish ethanolic extract of propolis (EEP) and its major component—CAPE—in interferon-alpha (IFN-α), lipopolysaccharide (LPS), LPS + IFN-α-induced human gingival fibroblasts (HGF-1). EEP and CAPE were used at 10–100 µg/mL. A multiplex assay was used for interleukin and adhesive molecule detection. Our results demonstrate that EEP, at a concentration of 25 µg/mL, decreases pro-inflammatory cytokine IL-6 in LPS-induced HGF-1. At the same concentration, EEP increases the level of anti-inflammatory cytokine IL-10 in LPS + IFN-α-induced HGF-1. In the case of CAPE, IL-6 in LPS and LPS + IFN-α induced HGF-1 was decreased in all concentrations. However, in the case of IL-10, CAPE causes the highest increase at 50 µg/mL in IFN-α induced HGF-1. Regarding the impact of EEP on adhesion molecules, there was a noticeable reduction of E-selectin by EEP at 25, 50, and100 µg/mL in IFN-α -induced HGF-1. In a range of 10–100 µg/mL, EEP decreased endothelin-1 (ET-1) during all stimulations. CAPE statistically significantly decreases the level of ET-1 at 25–100 µg/mL in IFN-α and LPS + IFN-α. In the case of intercellular adhesion molecule-1 (ICAM-1), EEP and CAPE downregulated its expression in a non-statistically significant manner. Based on the obtained results, EEP and CAPE may generate beneficial cardiovascular effects by influencing selected factors. EEP and CAPE exert an impact on cytokines in a dose-dependent manner. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to analyse the concentration of the nerve growth factor (NGF-β) in patients with keratoconus (KC) who are undergoing collagen fibre cross-linking (CXL) surgery in order to better understand the pathogenesis of this disease and observe the molecular changes occurring after the procedure. Among many cytokines, β-NGF seems to play an important role in the healing processes of corneal damage. Therefore, its role in the regenerative process after CXL treatment may affect the course of treatment and its final results. Tear samples from 52 patients were collected in this prospective study. Additionally, the patients also had a number of tests performed, including corneal topography using optical coherence tomography. Flat (K 1), steep (K 2), cylindrical (CYL), and central corneal thickness (CCT) keratometry were assessed. The tear samples were collected, and other tests were performed before the CXL procedure and afterwards, during the 12-month follow-up period. The NGF concentration was measured using the Bio-Plex Magnetic Luminex Assay. Lower levels of NGF-β were detected in the KC patients than in the control group (p < 0.001). The day after the procedure, the NGF-β level was significantly lower (on average by 2.3 pg/mL) (p = 0.037) than before the procedure, after which, the level of the reagent increases, but only in the group with the advanced cone, one month after CXL it was significantly higher (p = 0.047). Regarding the correlation of NGF with topographic measurements, the following were found: NGF-β correlates significantly (p < 0.05) and positively (r > 0) with K1 before the CXL procedure; NGF-β correlates significantly (p < 0.05) and positively (r > 0) with K1 one month after CXL; NGF-β correlates significantly (p < 0.05) and positively (r > 0) with CYL nine months after CXL; and, after twelve months, NGF-β correlates significantly (p < 0.05) and positively (r > 0) with K2 and K1. Corneal sensitivity did not statistically and significantly correlate with the level of NGF-β secretion. Our study suggests that NGF may be crucial in the development and progression of KC as well as in the repair mechanisms after CXL surgery. Further research is needed on the role of NGF and other inflammatory biomarkers for rapid diagnosis and selection of targeted therapy in patients with keratoconus. [ABSTRACT FROM AUTHOR]

In 2020, there were 377,713 new oral and lip cancer diagnoses and 177,757 deaths. Oral cancer is a malignancy of the head and neck region, and 90% of cases are squamous cell carcinomas (OSCCs). One of the alternative methods of treating pre-cancerous lesions and oral cancer is photodynamic therapy (PDT). In addition to the cytotoxic effect, an important mechanism of PDT action is the immunomodulatory effect. This study used the OSCC (SCC-25) cell line and the healthy gingival fibroblast (HGF-1) line. A compound of natural origin—hypericin (HY)—was used as the photosensitizer (PS). The HY concentrations of 0–1 µM were used. After two hours of incubation with PS, the cells were irradiated with light doses of 0–20 J/cm2. The MTT test determined sublethal doses of PDT. Cell supernatants subjected to sublethal PDT were assessed for interleukin 6 (IL-6), soluble IL-6 receptor alpha (sIL-6Ralfa), sIL-6Rbeta, IL-8, IL-10, IL-11 IL-20, IL-32, and Pentraxin-3 using the Bio-Plex ProTM Assay. The phototoxic effect was observed starting with a light dose of 5 J/cm2 and amplified with increasing HY concentration and a light dose. HY-PDT affected the SCC-25 cell secretion of sIL-6Rbeta, IL-20, and Pentraxin-3. HY alone increased IL-8 secretion. In the case of HGF-1, the effect of HY-PDT on the secretion of IL-8 and IL-32 was found. [ABSTRACT FROM AUTHOR]

Inflammation plays an important role in the immune defense against injury and infection agents. However, the inflammatory chronic process may lead to neurodegenerative diseases, atherosclerosis, inflammatory bowel diseases, or cancer. Flavanones present in citrus fruits exhibit biological activities, including anti-oxidative and anti-inflammatory properties. The beneficial effects of flavanones have been found based on in vitro cell cultures and animal studies. A suitable in vitro model for studying the inflammatory process are macrophages (RAW264.7 cell line) because, after stimulation using lipopolysaccharide (LPS), they release inflammatory cytokines involved in the immune response. We determined the nitrite concentration in the macrophage cell culture and detected ROS using chemiluminescence. Additionally, we measured the production of selected cytokines using the Bio-Plex Magnetic Luminex Assay and the Bio-PlexTM 200 System. For the first time, we have shown that methyl derivatives of flavanone inhibit NO and chemiluminescence generated via LPS-stimulated macrophages. Moreover, the tested compounds at 1–20 µM dose-dependently modulate proinflammatory cytokine production (IL-1β, IL-6, IL-12p40, IL-12p70, and TNF-α) in stimulated RAW264.7 cells. The 2′-methylflavanone (5B) and the 3′-methylflavanone (6B) possess the strongest anti-inflammatory activity among all the tested flavanone derivatives. These compounds reduce the concentration of IL-6, IL-12p40, and IL12p70 compared to the core flavanone structure. Moreover, 2′-methylflavanone reduces TNF-α, and 3′-methylflavanone reduces IL-1β secreted by RAW264.7 cells. [ABSTRACT FROM AUTHOR]