Serum Levels Of MCP-1 Research Articles

Associations between Various Inflammatory Markers and Carotid Findings in a Voluntary Asymptomatic Population Sample.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide, and atherosclerosis is the key factor promoting its development. Carotid intima-media thickening and the presence of carotid plaques are important indices of cardiovascular risk. In addition, inflammation is a major and complex factor in the development of atherosclerosis. The relationships between carotid atherosclerosis and certain inflammatory markers have rarely been studied in healthy individuals. Therefore, we aimed to investigate the associations between subclinical carotid atherosclerosis and various inflammatory biomarkers in a large Caucasian population free of evident CVD. In addition to recording study participants' demographic characteristics, anthropometric characteristics, and atherosclerotic risk factors, laboratory tests were performed to measure levels of hemoglobin A1c (HbA1c), high-sensitivity C-reactive protein, and inflammatory cytokines/chemokines, including interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-18, IL-23, IL-33, interferon (IFN)-α2, IFN-γ, tumor necrosis factor-α, and monocyte chemoattractant protein (MCP)-1. This study included 264 asymptomatic individuals with a median age of 61.7 years (interquartile range, 54.5-67.5 years); 45.7% of participants were male. Participants were divided into two groups according to their carotid status: the normal carotid group, comprising 120 participants; and the pathological carotid group, comprising 144 participants. Compared with the normal carotid group, hypertension and diabetes mellitus were significantly more common and serum levels of HbA1c, IL-8, and MCP-1 were significantly higher in the pathological carotid group. Multivariate regression analysis revealed significant positive associations between pathological carotid findings and serum levels of IL-8 (highest tertile, OR: 2.4, p = 0.030) and MCP-1 (highest tertile, OR: 2.4, p = 0.040). Our results suggest that IL-8 and MCP-1 may serve as early indicators of subclinical atherosclerosis, thereby helping to identify individuals at increased risk of CVD before the onset of clinical symptoms.

Jiegeng decoction ameliorated acute pharyngitis through suppressing NF-κB and MAPK signaling pathways

Ethnopharmacological relevanceJiegeng decoction (JGD), consisting of Glycyrrhizae Radix et Rhizoma and Platycodonis Radix at the ratio of 2:1, is a classical Chinese medicine prescription firstly recorded in “Treatise on Febrile Diseases”. JGD has been extensively utilized to treat sore throat and lung diseases for thousands of years in China. However, the pharmacological effect and mechanism of JGD on acute pharyngitis (AP) remain unclear. Aim of the studyOur research aimed to reveal the pharmacological effect of JGD on AP and its potential mechanisms. Materials and methodsThe chemical components of JGD were analyzed based on the UPLC-MS analysis. The anti-inflammatory effect of JGD was evaluated by NO production using the Griess assay in RAW 264.7 cells. The mRNA expression of iNOS, IL-1β, IL-10, TNF-α, IL-6 and MCP-1 was determined by qRT-PCR in vitro. A 15% ammonia-induced AP model was established. The histopathology, the inflammatory cytokines IL-6 and MCP-1 in serum and the apoptosis-related genes caspease-8 and caspease-3 were determined by H&E staining, ELISA and qRT-PCR, respectively. The expression levels of p-p65, p65, p-JNK, JNK, p-p38, p38, p-ERK1/2, ERK1/2, and COX2 were measured through western blotting. ResultsNine compounds, including liquiritin, liquiritin apiosde, liquiritigenin, platycodin D, platycoside A, licorice saponin J2, licorice saponin G2, glycyrrhizic acid, and licochalcone A, were identified. JGD significantly inhibited NO production and regulated the mRNA expression levels of cytokines in LPS-stimulated RAW 264.7 cells. The results of in vivo experiments confirmed that JGD ameliorated AP through improving the pathological state of pharyngeal tissue, decreasing the serum levels of IL-6 and MCP-1 and preventing the tissue mRNA expression of caspease-8 and caspease-3. Furthermore, JGD also inhibited the NF-κB and MAPK pathways in the AP model. ConclusionsThis study suggested that JGD could alleviate AP through its anti-inflammation via NF-κB and MAPK pathways, which supported the traditional application of JGD for the treatment of throat diseases.

Assessing the Ability to Reverse High Fat High Sugar Diet-Induced Hepatic Steatosis by Dietary Modification

Background: Metabolic syndrome includes a plethora of symptoms ultimately leading to obesity and type 2 diabetes. Increased consumption of ‘Western diets’ rich in fat and sugar increase the development of metabolic syndrome, diabetic obesity and furthermore increase the risk of non-alcoholic fatty liver disease. We aimed to better understand the influence of chronic consumption of a ‘western-type’ high fat-high sugar diet (HFS) on hepatic health and moreover we assessed the ability of dietary modifications (i.e., removal of fat and sugar from the diet) to reverse these detrimental hepatic effects. This would represent what is seen clinically, advocated by a provider in a clinical setting as a first line treatment for diabetic obese patients. Methods: Thirty male C57BL/6J mice were randomly assigned into the following groups: 12-weeks HFS then 12-weeks of standard diet and water (Std), control groups were fed standard chow and water for the entire 24-weeks (lean control) or fed HFS diet for the entire 24-weeks (HFS). At the end of the 24-week diet study, livers were removed and fixed (for sectioning and staining with Oil-Red-O or trichrome and quantified with Image J) or frozen and kept at -80°C (for PCR studies and assays). Serum was collected for assays. Results: At the end of the diet study, body weight was significantly increased 1.5-fold by HFS and reduced 34% (p<0.05) in the Std group. Liver weight/body weight ratio followed the same trend as body weight. Percent fat area, total number of lipid droplets and average total lipid area were all significantly increased in the HFS group versus lean controls and were all significantly reduced by Std (p<0.05). Serum ALT activity was increased 3-fold by HFS and then reduced to lean levels by Std. Serum TNF-α and MCP1 levels followed the same trend. Serum TBARS were significantly increased 1.6-fold, but unchanged with Std. Trichrome analysis demonstrated deposition of collagen in liver from HFS fed mice (15.53% area), which was significantly reversed by the switch to Std (4.58% area). This data will be complemented with mRNA levels currently being run for collagens 1, 3, 4. Preliminary findings indicate that HFS fed mice have a significant increase in expression of collagen-1 but not collagen-3. We aim to further explore the metabolic mechanisms involved in the reversal of hepatic steatosis and fibrosis between the three diet groups. Conclusions: We conclude that removal of the HFS diet and switching to standard chow and water (Std) is an effective treatment regimen and results in robust reversal of hepatic steatosis along with reversal of collagen deposition, with concomitant beneficial changes in key serum markers of hepatic health, systemic inflammatory profile, and body/liver weight. The mechanistic pathways triggering these effects are being explored. Midwestern-Arizona Alzheimer’s consortium and Midwestern University Intramural Grant. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Correlation between serum inflammatory factors and cognitive function in patients with high-altitude polycythemia: A case-control study.

The purpose of this study is to investigate the serum inflammatory factors in patients with high-altitude polycythemia (HAPC) and their correlation with cognitive function. The subjects were recruited and placed into a HAPC group and control group. Serum samples were collected, and inflammatory factors (interleukin-1beta [IL-1β], monocyte chemoattractant protein-1 [MCP-1], and tumor necrosis factor-alpha [TNF-α]) were measured using ELISA kits. The mini-mental State Examination (MMSE) was used to assess cognitive function. According to the MMSE scores, HAPC group was further divided into normal cognitive function group (HNCF) and cognitive dysfunction group (HCDF). In comparison with the control group, the MMSE scores in the HAPC group were significantly low (P < .05), whereas the serum levels of IL-1β, MCP-1, and TNF-α were significantly high (P < .01). Among the HAPC group (n = 60), 21 belonged to the HCDF and 39 belonged to the HNCF. Compared with the HNCF, the IL-1β, MCP-1, and TNF-α in the HCDF were significantly increased (P < .01). The Pearson correlation analysis showed that inflammatory factors were positively correlated with hemoglobin, and negatively correlated with MMSE. Serum inflammatory cytokines IL-1, MCP-1, and TNF-α were increased in HAPC, and HAPC exhibited cognitive dysfunction. Considering chronic hypoxia environment influences the change of the red blood cell metabolic and inflammatory factor, red blood cells and inflammatory factor in plateau is likely to be affected by patients with vascular lesions, increase cognitive impairment.

The impact and inflammatory characteristics of SARS-CoV-2 infection during ovarian stimulation on the outcomes of assisted reproductive treatment.

Despite the global prevalence of coronavirus disease 2019 (COVID-19), limited research has been conducted on the effects of SARS-CoV-2 infection on human reproduction. The aims of this study were to investigate the impact of SARS-CoV-2 infection during controlled ovarian stimulation (COS) on the outcomes of assisted reproductive treatment (ART) and the cytokine status of patients. This retrospective cohort study included 202 couples who received ART treatment, 101 couples infected with SARS-CoV-2 during COS and 101 matched uninfected couples. The parameters of ovarian stimulation and pregnancy outcomes were compared between the two groups. The All-Human Inflammation Array Q3 kit was utilized to measure cytokine levels in both blood and follicular fluid. No difference was found in the number of good-quality embryos (3.3 ± 3.1 vs. 3.0 ± 2.2, P = 0.553) between the infected and uninfected groups. Among couples who received fresh embryo transfers, no difference was observed in clinical pregnancy rate (53.3% vs. 51.5%, P = 0.907). The rates of fertilization, implantation, miscarriage, ectopic pregnancy and live birth were also comparable between the two groups. After adjustments were made for confounders, regression models indicated that the quality of embryos (B = 0.16, P = 0.605) and clinical pregnancy rate (P = 0.206) remained unaffected by SARS-CoV-2 infection. The serum levels of MCP-1, TIMP-1, I-309, TNF-RI and TNF-RII were increased, while that of eotaxin-2 was decreased in COVID-19 patients. No significant difference was found in the levels of cytokines in follicular fluid between the two groups. Asymptomatic or mild COVID-19 during COS had no adverse effects on ART outcomes. Although mild inflammation was present in the serum, it was not detected in the follicular fluid of these patients. The subsequent immune response needs further investigation.

Innate Responses to the Former COVID-19 Vaccine Candidate CVnCoV and Their Relation to Reactogenicity and Adaptive Immunogenicity.

Vaccines are highly effective at preventing severe coronavirus disease (COVID-19). With mRNA vaccines, further research is needed to understand the association between immunogenicity and reactogenicity, which is defined as the physical manifestation of an inflammatory response to a vaccination. This study analyzed the immune response and reactogenicity in humans, post immunization, to the former SARS-CoV-2 mRNA investigational vaccine CVnCoV (CV-NCOV-001 and CV-NCOV-002 clinical trials). Immunogenicity was investigated using whole-blood RNA sequencing, serum cytokine levels, and SARS-CoV-2-specific antibodies. The T cell responses in peripheral blood were assessed using intracellular cytokine staining (ICS) and high-dimensional profiling in conjunction with SARS-CoV-2 antigen-specificity testing via mass cytometry. Reactogenicity was graded after participants' first and second doses of CVnCoV using vaccine-related solicited adverse events (AEs). Finally, a Spearman correlation was performed between reactogenicity, humoral immunity, and serum cytokine levels to assess the relationship between reactogenicity and immunogenicity post CVnCoV vaccination. Our findings showed that the gene sets related to innate and inflammatory immune responses were upregulated one day post CVnCoV vaccination, while the gene sets related to adaptive immunity were upregulated predominantly one week after the second dose. The serum levels of IFNα, IFNγ, IP-10, CXCL11, IL-10, and MCP-1 increased transiently, peaking one day post vaccination. CD4+ T cells were induced in all vaccinated participants and low frequencies of CD8+ T cells were detected by ex vivo ICS. Using mass cytometry, SARS-CoV-2 spike-specific CD8+ T cells were induced and were characterized as having an activated effector memory phenotype. Overall, the results demonstrated a positive correlation between vaccine-induced systemic cytokines, reactogenicity, and adaptive immunity, highlighting the importance of the balance between the induction of innate immunity to achieve vaccine efficacy and ensuring low reactogenicity.

Immunological Biomarkers IL-34, MCP-1, and MIP-1α: Age and Sex Associations in Periodontitis Patients

Periodontitis is a common osteolytic disease and the leading cause of adult tooth loss. The disease's susceptibility can be influenced by systemic factors, with age and sex being significant factors. The current study assessed the correlations between interleukins and age and sex in periodontitis patients. A total of 85 periodontitis patients and 40 healthy individuals aged between 18 and 67 years were included to examine statistical correlations between interleukins and age/sex in periodontitis. Using ELISA techniques, levels of IL-34, MCP-1, and MIP-1α in serum and gingival crevicular fluid (GCF) were assessed. Statistical analyses, including the Kruskal-Wallis Test, Mann-Whitney Test, and Chi-square Test, were conducted to ascertain relationships among immunological markers, age, and sex, with significance set at P≤0.05. The results revealed significant age correlations with IL-34 concentrations in serum and GCF, notably increasing in patients aged 40-54. Conversely, no substantial age-based variances were observed in MCP-1 or MIP-1α levels within the patient group. Sex effect on IL-34 production, demonstrating higher levels in patients compared to healthy individuals. Conversely, MCP-1 and MIP-1α levels showed no significant sex-related variations within patients. In conclusion, this study underscores a positive association between age and IL-34 levels in serum and GCF among periodontitis patients. Additionally, it underscores the sex impact on IL-34 production. These findings contribute to comprehending the immunological mechanisms of periodontitis and the role of age and sex in disease susceptibility. Further exploration is needed to assess these findings' implications in tailoring personalized treatment approaches for periodontitis.

Interleukin-2/anti-interleukin-2 complex attenuates inflammation in a mouse COPD model by expanding CD4+ CD25+ Foxp3+ regulatory T cells

Background and purposeChronic, nonspecific inflammation of the alveoli and airways is an important pathological feature of chronic obstructive pulmonary disease (COPD), while sustained inflammatory reactions can cause alveolar damage. Regulatory T cells (Tregs) inhibit inflammation, whereas the interleukin-2/anti-interleukin-2 complex (IL-2C) increases the number of Tregs; however, whether the IL-2C has a therapeutic role in COPD remains unknown. Therefore, this study investigated whether IL-2C alleviates lung inflammation in COPD by increasing the number of Tregs. Experimental approachA mouse COPD model was created by exposing mice to lipopolysaccharides (LPS) and cigarette smoke (CS), and the effects of IL-2C treatment on COPD were evaluated. The number of Tregs in the spleen and lung, pulmonary pathological changes, and inflammatory damage were examined through flow cytometry, histopathology, and immunofluorescence, respectively. Key resultsIL-2C increased the number of Treg cells in the spleen and lungs after exposure to CS and LPS, reduced the number of T helper 17 (Th17) cells in lung tissue, and improved the Th17/Treg balance. IL-2C decreased the number of inflammatory cells and reduced the levels of pro-inflammatory cytokines IL-6, TNF-α, IL-1β, CCL5, KC, and MCP-1 in bronchoalveolar lavage fluid and serum. IL-2C significantly reduced the pathological scores for lung inflammation, as well as decreased airway mucus secretion and infiltration of neutrophils and macrophages in the lungs. The depletion of Tregs using anti-CD25 antibodies eliminated the beneficial effects of IL-2C. Conclusions and implicationsIL-2C is a potential therapeutic agent for alleviating excessive inflammation in the lungs of patients with COPD.

Human Bronchial Epithelial Cell Transcriptome Changes in Response to Serum from Patients with Different Status of Inflammation

PurposeTo investigate the transcriptome of human bronchial epithelial cells (HBEC) in response to serum from patients with different degrees of inflammation.MethodsSerum from 19 COVID-19 patients obtained from the Hannover Unified Biobank was used. At the time of sampling, 5 patients had a WHO Clinical Progression Scale (WHO-CPS) score of 9 (severe illness). The remaining 14 patients had a WHO-CPS of below 9 (range 1–7), and lower illness. Multiplex immunoassay was used to assess serum inflammatory markers. The culture medium of HBEC was supplemented with 2% of the patient’s serum, and the cells were cultured at 37 °C, 5% CO2 for 18 h. Subsequently, cellular RNA was used for RNA-Seq.ResultsPatients with scores below 9 had significantly lower albumin and serum levels of E-selectin, IL-8, and MCP-1 than patients with scores of 9. Principal component analysis based on 500 “core genes” of RNA-seq segregated cells into two subsets: exposed to serum from 4 (I) and 15 (II) patients. Cells from a subset (I) treated with serum from 4 patients with a score of 9 showed 5566 differentially expressed genes of which 2793 were up- and 2773 downregulated in comparison with cells of subset II treated with serum from 14 patients with scores between 1 and 7 and one with score = 9. In subset I cells, a higher expression of TLR4 and CXCL8 but a lower CDH1, ACE2, and HMOX1, and greater effects on genes involved in metabolic regulation, cytoskeletal organization, and kinase activity pathways were observed.ConclusionThis simple model could be useful to characterize patient serum and epithelial cell properties.

Inhibitory effect of Incarvillea diffusa Royle extract in the formation of calcium oxalate nephrolithiasis by regulating ROS-induced Nrf2/HO-1 pathway in rats

Ethnopharmacological relevanceCalcium oxalate (CaOx) kidney stones are widely acknowledged as the most prevalent type of urinary stones, with high incidence and recurrence rates. Incarvillea diffusa Royle (ID) is a traditionally used medicinal herb in the Miao Minzu of Guizhou province, China, for treating urolithiasis. However, the active components and the underlying mechanism of its pharmacodynamic effects remain unclear. Aim of the studyThis study aimed to investigate the potential inhibitory effect of the active component of ID on the formation of CaOx nephrolithiasis and elucidate the underlying mechanism. Materials and methodsIn vivo, a CaOx kidney stone model was induced in Sprague-Dawley (SD) rats using an ethylene glycol and ammonium chloride protocol for four weeks. Forty-eight male SD rats were randomly assigned to 6 groups (n = 8): blank group, model group, apocynin group, and low, medium, and high dose of ID's active component (IDW) groups. After three weeks of administration, rat urine, serum, and kidney tissues were collected. Renal tissue damage and crystallization, Ox, BUN, Ca2+, CRE, GSH, MDA, SOD contents, and levels of IL-1β, IL-18, MCP-1, caspase-1, IL-6, and TNF-α in urine, serum, and kidney tissue were assessed using HE staining and relevant assay kits, respectively. Protein expression of Nrf2, HO-1, p38, p65, and Toll-4 in kidney tissues was quantified via Western blot. The antioxidant capacities of major compounds were evaluated through DPPH, O2·-, and ·OH radical scavenging assays, along with their effects on intracellular ROS production in CaOx-induced HK-2 cells. ResultsWe found that IDW could significantly reduce the levels of CRE, GSH, MDA, Ox, and BUN, and enhancing SOD activity. Moreover, it could inhibit the secretion of TNF-α, IL-1β, IL-18, MCP-1, caspase-1, and decreased protein expression of Nrf2, HO-1, p38, p65, and Toll-4 in renal tissue. Three major compounds isolated from IDW exhibited promising antioxidant activities and inhibited intracellular ROS production in CaOx-induced HK-2 cells. ConclusionsIDW facilitated the excretion of supersaturated Ca2+ and decreased the production of Ox, BUN in SD rat urine, and mitigated renal tissue damage by regulating Nrf2/HO-1 signaling pathway. Importantly, the three major compounds identified as active components of IDW contributed to the inhibition of CaOx nephrolithiasis formation. Overall, IDW holds significant potential for treating CaOx nephrolithiasis.

The role of gene expression hypoxia-inducible factor-1a and serum level monocyte chemoattractant protein-1 in the incidence of chronic myeloid leukemia in Iraqi patients

Abstract: BACKGROUND: Chronic myeloid leukemia (CML) is a hematopoietic stem cell malignancy described by a translocation between chromosomes 9 and 22. There are many factors genetic or nongenetic effect on disease progression such as growth factors and transcription factors act as oncogenes or tumor suppressor genes. OBJECTIVES: The purpose of this research was to investigate the role of hypoxia-inducible factor (HIF1A) gene expression with CML, as well as the role of monocyte chemoattractant protein-1 (MCP-1) as a predictive biomarker on disease progression. MATERIALS AND METHODS: The current study consists of three groups: first group includes 50 newly diagnosed CML patients (females 22 and males 28), second group consists of 50 CML patients treated with tyrosine kinase inhibitor (TKI) with a complete molecular response (p210 BCR-ABL transcript levels ≤0.1% IS) (female 25 and male 25), and third group included another 50 apparently healthy volunteers (female 20 and male 30). The patients were admitted from the National Center of Hematology/Mustansiriyah University. All patients are diagnosed according to a complete blood count (CBC), a bone marrow examination, and a BCR-ABL gene test. RESULTS: Reverse transcription-quantitative polymerase chain reaction was applied to assess the expression levels of the HIF-1A gene and serum level of MCP1 by enzyme-linked immunosorbent assay. The results displayed downregulated of the HIF1A gene messenger RNA in CML patients in comparison to the controls group, as well as no statistically significant link was discovered when the fold of expression was correlated with the age and gender of CML patients. CONCLUSION: HIF1-alpha gene has an important role in pathological pathways such as angiogenesis. According to this study, HIF1-alpha gene is not an appropriate prognostic biomarker for detecting the risk of CML as well as MCP1 is thought to be a predictor of CML progression.

The Effects of High Fat Diet on the Incidence of Obesity and Monocyte Chemoattractant Protein-1 Levels on Histological Changes in Prostate Wistar Rats.

Benign prostatic hyperplasia (BPH) is a histopathological diagnosis characterized by the increase in stromal cells and epithelial cells of the prostate gland in the transitional zone surrounding the urethra. Obesity is the risk factor of BPH. The most frequent cause of obesity is a high-fat diet (HFD). Obesity and HFD lead to pro-inflammatory conditions. One of the pathomechanisms for the occurrence of BPH is a low-degree inflammatory factor, one of which is the level of monocyte chemoattractant protein-1/MCP-1. This study aims to determine the influence of HFD on the incidence of obesity and inflammatory factors (monocyte chemoattractant protein-1/MCP-1 levels) on the histopathological picture of the prostate. Experimental research was performed on male Wistar rats with each of the 6 rats given normal fat (ND) and HFD intake and terminated at 8 weeks and 6 rats given each ND and HFD were terminated at 16 weeks. The determination of obesity was determined based on Lee's criteria which were categorized as obese if the Lee index >0.3 and non-obese if ≤0.3. Examination of circulating MCP-1 was carried out by the ELISA method and determination of prostatic hyperplasia was done by calculating the percentage of prostate glands that had a large per-field cystic dilatation on light microscopy examination. All data are analyzed statistically with the Fisher Exact Test and Spearman Correlation Test. Of the 12 rats that were given ND, none of them became obese according to Lee's criteria, on the other hand, of the 12 rats that were given HFD 8 became obese (66.7%, p = 0.001). Serum MCP-1 levels and the percentage of prostate glands that had cystic dilatation were significantly higher in mice receiving HFD than ND; both at week-8 (MCP-1; 18.87 vs 15.66) and (prostate gland experiencing cystic dilatation; 63.46% vs 47.24%) and week-16 (MCP-1; 21.27 vs 21.27) and (prostate gland experiencing cystic dilatation; 67.79% vs 56.39%). Spearman correlation analysis showed that only circulating MCP-1 levels were significantly correlated (p < 0.05) to the percentage of the prostate gland that had cystic dilatation; especially in week 16 (r = 0.713 and p < 0.001). At 8 weeks, it was not statistically significant (r = 0.406 and p = 0.095). High fat intake has been shown to increase the risk of obesity, but obesity does not increase inflammatory status and the incidence of prostate glands with cystic dilatation. On the other hand, high-fat intake increases inflammatory status which in turn causes prostate glands to develop cystic dilatation.

Postmenopausal Lumbar Spine Osteoporosis in Hungarian Women is Characterised By Increased Serum Levels of Nerve Growth Factor

Purpose: In addition to its neuronal specificity, nerve growth factor (NGF) plays a role in immuno-inflammatory events. Cells involved in osteoporosis, in particular mesenchymal stem/stromal cells and monocytes/macrophages, are capable of producing NGF. The question was whether NGF might be involved in osteoporotic bone loss independent of age. Methods: Sixty postmenopausal Hungarian women were studied for serum NGF-β and MCP-1 levels, total lumbar spine and forearm osteoporosis, and femoral neck osteoporosis. Biochemical data were measured by enzyme-linked immunosorbent assay and presented as geometric mean (95% CI). Dual-energy X-ray absorptiometry was used to measure bone mineral density (BMD) and T-score values in three bone regions. Multiple regression analysis was used to identify the independent variables involved in the elevated NGF-β levels. Results: Serum NGF-β levels were significantly increased in the osteoporotic subgroup compared to the normal and osteopenic subgroups [15.85(8.99-27.91) vs. 12.42(8.28-18.64) pg/ml, p&lt;0.004 and 12.49(9.36-16.65) pg/ml, p&lt;0.002, respectively] in the total lumbar spine region. Using multiple regression analysis, serum MCP-1 levels alone and their interaction with lumbar spine BMD were significant with elevated serum NGF-β levels, age was not included in the model. Increased serum NGF-β levels were restricted to the lumbar spine, but not to forearm and femoral neck osteoporosis. Conclusion: Increased serum NGF-β levels were associated with the severity of lumbar spine osteoporosis. Increased sympathetic and sensory neural activity may contribute to the presence of pain and neuropathy in osteoporosis.

Multiple cytokine analyses identify CSF1 as a robust biomarker for predicting postoperative recurrence in chronic rhinosinusitis with nasal polyps

ObjectiveChronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous disease with a high rate of postoperative recurrence. This study aimed to discover potential biomarkers by analyzing multiple cytokine profiles in serum to predict postoperative recurrence in CRSwNP and to explore the underlying mechanisms. MethodsIn this prospective study, we enrolled 18 healthy controls (HC) and 60 CRSwNP patients and analyzed the baseline serum cytokine profiles using the Luminex assay. Patients were followed up for more than 2 years and divided into non-recurrence and Recurrence groups. The differentially expressed cytokines were validated in the serum and tissue samples in a validation cohort, and their predictive values for recurrence were evaluated. ResultsFifty-four CRSwNP patients completed the follow-up schedule, including 37 patients in the non-Recurrence group and 17 patients in the Recurrence group. Multiple cytokine analyses showed that serum CD40, CD40L, IL-18, IL-8, MCP1, and CSF1 levels were elevated in the CRSwNP group, especially in the Recurrence group, compared to the HC group. Receiver operating characteristic curves (ROC) and Kaplan-Meier survival analysis showed that serum levels of CD40, CD40L, and CSF1 were closely associated with the risk of postoperative recurrence. Further validation results showed that both serum and tissue mRNA levels of CD40, CD40L, and CSF1 were significantly higher in the Recurrence group in comparison with the non-recurrence and HC groups, and tissue CSF1 mRNA expression exhibited a robust value for predicting the CRSwNP recurrence. Immunofluorescence results revealed that CSF1 was enhanced in the recurrent CRSwNP patients, especially in the epithelial cell area, and CSF1 expressions were augmented when patients suffered postoperative recurrence. ConclusionsCirculating cytokine profiles may affect the risk of postoperative recurrence in CRSwNP patients. Our discovery-validation results suggested that CSF1 might serve as a robust biomarker for predicting CRSwNP recurrence.

Xuelian injection ameliorates complete Freund's adjuvant-induced acute arthritis in rats via inhibiting TLR4 signaling

BackgroundXuelian injection (XI), a classic preparation extracted from Saussureae Involucratae Herba, has been clinically used to manage rheumatoid arthritis (RA) for nearly twenty years in China. However, the underlying anti-RA mechanism of XI remains unclear. In this study, complete Freund's adjuvant (CFA)-induced acute arthritic model was used to examine the anti-RA effects of XI in vivo. The molecular mechanisms of this action were further investigated using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. MethodsXI and XI freeze dried powder were characterized by UPLC analysis. CD68 and TLR4 expression in the ankle joints was measured by immunohistochemistry. The secretion of inflammatory mediators was detected by ELISA. The expression levels of TLR4 involved components were measured by Western blotting. The localization of transcription factors was measured by immunofluorescence assay. ResultsXI treatment ameliorated arthritic symptoms induced by CFA in the ankle joints of rats. The serum levels of inflammatory mediators, including TNF-α, MCP-1, and Rantes were decreased by XI treatment. The elevation of CD68 and TLR4 levels in ankle joints caused by CFA was suppressed by XI treatment. Moreover, XI treatment inhibited the secretion of nitric oxide and prostaglandin E2 in LPS-treated RAW264.7 macrophages. The expression of their enzymes iNOS and COX-2 was also decreased after XI treatment. The production of inflammatory mediators, including TNF-α, IL-6, IL-1β, MCP-1, MIP-1α, and Rantes was reduced by XI treatment in LPS-stimulated RAW264.7 cells. The phosphorylation of p38, JNK, ERK, TBK1, IKKα/β, IκB, p65, c-Jun, and IRF3 was reduced after XI treatment. Additionally, the expression levels of nuclear proteins of p65, c-Jun, and IRF3 were inhibited by XI treatment. ConclusionsTaken together, XI possesses potential anti-RA effect and the underlying mechanism may be closely associated with the inhibition of TLR4 signaling. Our findings provide further pharmacological justifications for the clinical use of XI in RA treatment.

THU488 Genetic Alterations In CREBRF Influence Prostate Cancer Survival And Impact Prostate Tissue Homeostasis In Mice

Abstract Disclosure: L.E. Pascal: None. K.A. Frahm: None. K. Skalitzky: None. D.B. DeFranco: None. L. Rigatti: None. R. Lu: None. T. Liu: None. Background: Risk factors for prostate cancer include age, environmental factors, race and ethnicity. Genetic variants in cyclic-adenosine-monophosphate-response-element-binding protein 3 regulatory factor (CREBRF) gene are frequently observed in Pacific Islanders, a population with elevated prostate cancer incidence. CREBRF has been shown to play a role in other cancers, however its function in prostate homeostasis and tumorigenesis has not been previously explored. Methods: Alterations in CREBRF were identified in prostate cancer patients via in silico analysis of several publicly available datasets through cBioPortal. Male Crebrf knockout mice were generated and examined for prostate defects at 4 months of age. Immunohistochemical staining of murine prostate sections was used to determine the impact of Crebrf knockout on proliferation, apoptosis, inflammation and blood vessel density in the prostate. Serum adipokine levels were measured using a Luminex Multiplex Assay. Results: CREBRF alterations were identified in up to 4.05% of prostate tumors and the mutations identified were categorized as likely damaging. Median survival of patients with CREBRF alterations was 41 months, compared to 131 months for patients without CREBRF alterations. In the murine model, the prostates of Crebrf knockout mice had reduced epithelial proliferation and increased TUNEL+ apoptotic cells. Circulating adipokines PAI-1 and MCP-1 were also altered in Crebrf knockout mice compared to age-matched controls. Conclusions: Prostate cancer patients with CREBRF alterations were associated with decreased overall survival suggesting that CREBRF may play a role in prostate tumorigenesis and progression. The murine knockout model demonstrated that CREBRF could modulate proliferation and apoptosis and macrophage density in the prostate. Serum levels of adipokines PAI-1 and MCP-1 were also altered and could contribute to the phenotypic changes observed in the prostates of Crebrf knockout mice. Future studies focused on populations susceptible to CREBRF mutations and mechanistic studies will be required to fully elucidate the potential role of CREBRF in prostate tumorigenesis. Presentation: Thursday, June 15, 2023

The Lasting Effects of COVID-19 on the Progression of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD).

It is estimated that around 30% of thepopulation living in Western countries has metabolic dysfunction-associated steatotic liver disease (MASLD), a spectrum of pathology (not attributed to alcohol/substance intake) initiated by steatosis and progression toward inflammation and irreversible fibrosis metabolic dysfunction-associated steatohepatitis (MASH). With inflammation being a key component of the transition to MASH, it raises the question of whether the ongoing COVID-19 pandemic, which has notoriously induced hyperinflammatory states, may influence the progression of MASLD. Specifically, it remains unclear if the potential chronic sequelae of COVID-19 in patients who recovered from it may increase the predisposition for MASH. Since MASH maintains a high risk for hepatocellular carcinoma, liver failure, and the need for a liver transplant, the potential additive effects of COVID-19 could prove critical to study. Thus, the objective of this study was to conduct a literature review to examine if COVID-19 could have chronic sequelae that affect the progression of MASLD pathogenesis. It was hypothesized that severe cases of COVID-19 could induce systemic inflammation, metabolic changes, and lasting gut microbiome alterations that lead to inflammatory and fibrotic changes in the liver, similar to those seen in MASH. A scoping review of the literature was conducted utilizing the PubMed database. Studies that examined hepatobiliary pathology, gut microbiome, systemic inflammation, metabolic changes, drug-induced liver injury (DILI), and hypoxia seen in COVID-19 were included. Human studies of adult cohorts, animal models, and in vitro experiments were included. Genetic components of MASLD were not examined. Exclusion criteria also encompassed any studies not referencing the hepatobiliary, gastrointestinal tract, portal system, or systemic circulation. Findings indicated a frequent trend of elevated liver enzymes, mild steatosis, Kupffer cell hyperplasia, and hepatobiliary congestion. It was found that direct cytopathic effects on hepatocytes were unlikely, but the direct viral insult of cholangiocytes was a potential complication. High serum levels of IL-1, TNF-a, and MCP-1, in COVID-19 were found as potential risk factors for MASH development. Hypoxia, altered lipid metabolism, and iatrogenic DILI were also proposed as potential precipitators of MASH development. Notably, lasting changes in gut microbiome were also frequently observed and correlated closely with those seen in MASH.

Reconditioned monocytes are immunomodulatory and regulate inflammatory environment in sepsis

Sepsis is caused by dysregulated immune response to severe infection and hyper inflammation plays a central role in worsening the disease. The immunomodulatory properties of mesenchymal stem cells (MSCs) have been evaluated as a therapeutic candidate for sepsis. Reconditioned monocytes (RM), generated from healthy human peripheral blood mononuclear cells (PBMCs) exhibit both macrophage and MSCs-like properties. RM were administered at different stages of sepsis in a mouse model. It reduced serum levels of IL6, MCP-1, IL-10, improved hypothermia, increased survival, and recovery from 0 to 66% when combined with antibiotics in the mouse model. The reduced human leucocyte antigen DR molecules expression on RM enables their co-culture with PBMCs of sepsis patients which resulted in reduced ROS production, and up-regulated TGF-β while down-regulating IL6, IL8, and IL-10 in-vitro. RM are potentially immunomodulatory, enhance survival in sepsis mouse model and modulate inflammatory behaviour of sepsis patient’s PBMCs.

Impact of an Okinawa/Nordic based diet on endocrinological and periodontal conditions in individuals with type 2 diabetes. A randomized case–control study

ObjectivesTo assess if the results following intake of a diet using an Okinawan-based Nordic diet (OBND) over one month differs in endocrinological, periodontal clinical outcome, and serum cytokine levels compared to a standard hospital care diet in individuals with diabetes type 2 (T2D) (control group).BackgroundScientific evidence suggests that the use of diet for individuals with T2D may be beneficial.MethodsParticipating individuals with T2D were randomly assigned to a test (OBND) (n = 14), or control group (n = 16). Anthropometric data, blood glucose levels, HbA1c levels, lipids, serum inflammation markers (CRP, and a routine panel of 24 cytokines), blood pressure, gingival bleeding on probing (BOP), probing pocket depths (PPD), and clinical attachment levels (CAL) were studied.ResultsStatistical analyses of baseline study data failed to demonstrate study group differences. The mean weight reduction was greater in the OBND group (4.1 kg) versus the control group (1.3 kg) (p < 0.01). The reduction in BMI was 1.4 kg/m2 in OBND (p < 0.001) and 0.5 kg/m2 in the control group, respectively (p < 0.01). Diastolic and systolic blood pressure reductions were greater in the OBND group than in the control group (p < 0.01). Periodontal study parameters (BOP % scores) and (PPD values) decreased (p < 0.001) overall with no between group differences. The OBND resulted in reduction of serum levels of IFNγ, Eotaxin IL-9, IP10,IL17a, MCP-1,m and PDFBB compared to the control diet.ConclusionsA strict T2D- diet provides an association between reduction in serum HbA1c and BOP scores. Serum levels decreases in IFNγ, Eotaxin IL-9, IP-10, IL17a. MCP-1, and PDFBB were only found in the test group.

Design, Synthesis, and Anti-Inflammatory Evaluation of a Novel PPARδ Agonist with a 4-(1-Pyrrolidinyl)piperidine Structure.

Peroxisome proliferator-activated receptor δ (PPARδ) is considered to be a pharmaceutical target to treat metabolic diseases including atherosclerosis, but there is no PPARδ agonist available for clinical use. We have previously reported the discovery of piperidinyl/piperazinyl benzothiazole derivatives as a new series of PPARδ agonists using docking-based virtual screening methods. In the present study, we found that introduction of a pyrrolidine group into the 4-position of their central piperidine rings enhances hPPARδ activity and subtype selectivity. This led to the discovery of 21 having strong PPARδ agonist activity (EC50 = 3.6 nM) with excellent ADME properties. Furthermore, 21 significantly suppressed atherosclerosis progression by 50-60% with reduction of the serum level of MCP-1 in LDLr-KO mice.