Serum Levels Of IL-6 Research Articles

Circulating Growth Factors and Cytokines Correlate with Temperament and Character Dimensions in Adolescents with Mood Disorders

Background/Objectives: The incidence of mood disorders in adolescents is increasing. Bipolar disorder is often misdiagnosed in the early stages of the disease due to the prevalence of depressive symptoms, while manic episodes occur later. Identifying predictors of diagnosis conversion could facilitate timely and appropriate treatment. Our study aimed to find correlations of selected peripheral protein levels with temperament and character traits in adolescents diagnosed with major depressive disorder and bipolar disorder. Methods: A group of adolescents and young adults diagnosed with major depressive disorder (MDD, n = 50) or bipolar disorder (BD, n = 24) was enrolled in the study during the exacerbation of symptoms and followed up over two years. Diagnosis conversion from MDD to BD was monitored. The Temperament and Character Inventory was applied, and BDNF, proBDNF, EGF, MIF, SCF, S100B, TNF-alpha, and IL-8 serum levels were measured. Spearman’s rank correlation analysis was conducted. Results: We found different patterns of correlations in MDD (TNF-alpha, IL-8, EGF, S100B with reward-dependence, self-directedness, and empathy) and BD (BDNF and EGF with persistence novelty-seeking and self-transcendence). Significant correlations were found in a group with diagnosis conversion. Conclusions: The findings of our study have the potential to significantly impact our understanding and treatment of mood disorders. Correlations obtained in the subgroup with diagnosis conversion may contribute to the development of prognostic markers in the future. Evaluating temperament and character traits alongside established biomarkers may offer a valuable method for predicting the conversion of mood disorders in adolescents, facilitating early and effective pharmacotherapy.

Pharmacological modulation of Sigma-1 receptor ameliorates pathological neuroinflammation in rats with diabetic neuropathic pain via the AKT/GSK-3β/NF-κB pathway.

Diabetic neuropathic pain (DNP) is a common complication of diabetes mellitus (DM) and is characterized by spontaneous pain and neuroinflammation. The Sigma-1 receptor (Sig-1R) has been proposed as a target for analgesic development. It is an important receptor with anti-inflammatory properties and has been found to regulate DNP. However, it is not known whether Sig-1R can ameliorate pathological neuroinflammation in DNP. The present study used a rat model of DNP and a highly selective agonist of Sig-1R to assess the effects of the protein on neuropathic pain in rats with type 2 diabetes mellitus. The rats were divided into Control, Model, Sig-1R agonist PRE-084 (0.3, 0.6, 1mg/kg), and metformin (Met, 20mg/kg) groups, with seven rats per group, and their body weight, fasting blood glucose, mechanical withdrawal threshold and thermal withdrawal latency were tested weekly for two weeks. After treatment with PRE-084, the pain thresholds in the DNP rats were significantly improved, together with pathological changes in the dorsal root ganglion, reductions in the serum levels of TNF-α, IL-1β, IL-6, MOD, and prostaglandin E2 (PGE2), and the activity of superoxide dismutase was increased. The mRNA levels of TNF-α, IL-1β, and cyclooxygenase 2 (COX-2) were reduced. Pharmacological inhibition of Sig-1R with BD1047 (10μM) abolished Sig-1R-mediated activation of lipopolysaccharide-treated BV-2 microglial cells. It was also found that PRE-084 increased phosphorylation of serine/threonine protein kinase B (AKT) and glycogen synthase kinase 3β (GSK-3β) at Ser9, inhibiting nuclear factor kappa B (NF-κB)-mediated neuroinflammation in the dorsal root ganglion, thus reducing DNP. The findings suggest that the effect of Sig-1R agonist PRE-084 on DNP may reduce the level of inflammation through the up-regulation of AKT/GSK-3β and down-regulation of the NF-κB signaling, thereby contributing to the treatment of the disease.

An animal model of severe acute respiratory distress syndrome for translational research

BackgroundDespite the fact that an increasing number of studies have focused on developing therapies for acute lung injury, managing acute respiratory distress syndrome (ARDS) remains a challenge in intensive care medicine. Whether the pathology of animal models with acute lung injury in prior studies differed from clinical symptoms of ARDS, resulting in questionable management for human ARDS. To evaluate precisely the therapeutic effect of transplanted stem cells or medications on acute lung injury, we developed an animal model of severe ARDS with lower lung function, capable of keeping the experimental animals survive with consistent reproducibility. Establishing this animal model could help develop the treatment of ARDS with higher efficiency.ResultsIn this approach, we intratracheally delivered bleomycin (BLM, 5 mg/rat) into rats’ left trachea via a needle connected with polyethylene tube, and simultaneously rotated the rats to the left side by 60 degrees. Within seven days after the injury, we found that arterial blood oxygen saturation (SpO2) significantly decreased to 83.7%, partial pressure of arterial oxygen (PaO2) markedly reduced to 65.3 mmHg, partial pressure of arterial carbon dioxide (PaCO2) amplified to 49.2 mmHg, and the respiratory rate increased over time. Morphologically, the surface of the left lung appeared uneven on Day 1, the alveoli of the left lung disappeared on Day 2, and the left lung shrank on Day 7. A histological examination revealed that considerable cell infiltration began on Day 1 and lasted until Day 7, with a larger area of cell infiltration. Serum levels of IL-5, IL-6, IFN-γ, MCP-1, MIP-2, G-CSF, and TNF-α substantially rose on Day 7.ConclusionsThis modified approach for BLM-induced lung injury provided a severe, stable, and one-sided (left-lobe) ARDS animal model with consistent reproducibility. The physiological symptoms observed in this severe ARDS animal model are entirely consistent with the characteristics of clinical ARDS. The establishment of this ARDS animal model could help develop treatment for ARDS.

Time-restricted feeding improves metabolic syndrome by activating thermogenesis in brown adipose tissue and reducing inflammatory markers

BackgroundObesity and metabolic syndrome (MetS) have become increasingly significant global health issues. Time-restricted feeding (TRF), as a novel dietary intervention, has garnered attention in recent years. However, there is limited research focusing on the effects of TRF on energy expenditure and systemic low-grade inflammation. This study aims to investigate the impact of TRF on weight management, glucose metabolism, insulin resistance, and lipid metabolism in male C57BL/6J mice, particularly in the context of metabolic disorders induced by a high-fat diet (HFD).MethodsC57BL/6J mice were divided into two groups: a normal diet (ND) group and a high-fat diet (HFD) group. The study duration was 12 weeks. Key parameters observed included body weight, glucose tolerance (via glucose tolerance tests), insulin resistance (HOMA-IR), and insulin secretion under glucose stimulation. Additionally, liver tissue was subjected to Oil Red O staining to assess lipid accumulation, and white and brown adipose tissues were stained with hematoxylin and eosin (HE) to evaluate adipocyte size. The expression of hepatic lipogenesis-related genes (Srebp-c, Chrebp, Fasn, and Acc1) and thermogenic genes in brown adipose tissue (UCP1 and PGC-1α) were also measured. Furthermore, temperature changes in the interscapular brown adipose tissue (BAT) were monitored.ResultsIn the ND group: TRF improved insulin resistance and reduced circulating levels of the pro-inflammatory cytokine IL-6, with a slight reduction in body weight.In the HFD group: TRF significantly mitigated weight gain, improved glucose tolerance and insulin resistance, and enhanced insulin secretion under glucose stimulation. Additionally, TRF reduced hepatic steatosis by downregulating the expression of lipogenesis-related genes in the liver. TRF also increased thermogenesis by upregulating the expression of thermogenic genes (UCP1 and PGC-1α) in BAT, while lowering serum levels of pro-inflammatory cytokines IL-6 and TNF-α, though IL-1β levels remained unchanged.ConclusionThis study demonstrates that TRF can activate thermogenesis in brown adipose tissue and reduce inflammation maker, leading to an improvement in hepatic steatosis and a reduction in white adipose tissue accumulation. These findings suggest that TRF may be a promising intervention for mitigating metabolic disturbances associated with obesity and metabolic syndrome. The study provides mechanistic insights into the beneficial effects of TRF, highlighting its potential in modulating lipid metabolism and exerting anti-inflammatory effects.

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

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

Association between serum levels of 12 different cytokines and short-term efficacy of chemoradiotherapy in esophageal squamous cell carcinoma

BackgroundEsophageal squamous cell carcinoma (ESCC) has a poor prognosis, with chemoradiotherapy (CRT) being a key treatment method. This study focused on circulating cytokines as potential predictors of treatment response and prognosis in patients with ESCC.Materials and methodsSerum samples were collected from 36 ESCC patients, and 12 different cytokines were quantified using a multiplex immunofluorescence assay. We used non-parametric Wilcoxon unpaired rank tests to examine the relationship between cytokine concentrations and clinical outcomes. The duration of progression-free survival was assessed through imaging studies and telephone follow-ups. Kaplan–Meier survival plots, analyzed with the log-rank test, were utilized to depict survival trends.ResultsPre-treatment serum IL-8 levels were significantly elevated in patients with lymphoid metastases (p = 0.036). Lower initial levels of IL-8 and IL-1β were observed in patients with partial response group compared to those with stable disease (p = 0.002, p = 0.01). Elevated baseline levels of IL-8 and interferon-gamma (IFN-γ) were correlated with a poorer prognosis. Higher levels of IL-5 and IFN-γ levels following therapy were associated with worse outcomes.ConclusionsOur findings indicate that IL-8, IL-1β, IL-5, and IFN-γ may serve as potential biomarkers for treatment efficacy and prognosis in ESCC. Patients with low levels of IL-8 and IL-1β demonstrate a favorable response to CRT. Elevated serum levels of IL-8, IL-1β, IFN-γ, and IL-5 may predict poorer clinical outcomes.

Unclosing Clinical Criteria and the Role of Cytokines in the Pathogenesis of Persistent Post-COVID-19 Headaches: A Pilot Case-Control Study from Egypt

(1) Background: Persistent post-COVID-19 headaches are emerging as a significant post-infection symptom. This study investigates the clinical characteristics of persistent post-COVID-19 headaches and the potential role of pro-inflammatory cytokines. (2) Methods: We conducted a pilot case–control study involving 84 participants divided into three groups: post-COVID with headache (n = 28), post-COVID without headache (n = 28), and healthy controls (n = 28). The detailed headache characteristics, including pain intensity, were assessed using the Visual Analog Scale (VAS). The serum levels of inflammatory cytokines (IL-6 and TNF-α) were measured. (3) Results: Post-COVID headaches predominantly presented as bilateral (53.6%) and throbbing (60.7%) in nature, with a median of 12 headache days per month and high pain intensity (median VAS score = 80). The associated symptoms were phonophobia (85.7%), fatigue (78.6%), and photophobia (75%). The serum levels of IL-6 and TNF-α were significantly higher in post-COVID headache patients than in the post-COVID without headache and healthy control groups (p < 0.001). A Receiver Operating Characteristic analysis showed that the circulating levels of IL-6 and TNF-α could discriminate our study groups at cutoffs with variable sensitivity and specificity. (4) Conclusions: Persistent post-COVID-19 headaches have diverse clinical characteristics and are associated with elevated circulating levels of pro-inflammatory cytokines, suggesting a potential underlying neuroinflammation.

P0431 Multiparametric Assessment of IBD, SpA and IBD-SpA patients to explore disease biomarkers and response predictors

Abstract Background Immune-mediated inflammatory diseases (IMID) can coexist within the same patient and their pathogenesis could overlap. Inflammatory bowel disease (IBD) [Crohn’s disease (CD) and ulcerative colitis (UC)], and spondylarthritis (SpA), often associate, but disease biomarkers are not fully characterized. This project aims to investigate a possible molecular signature of disease and predictor markers of response Methods We performed an observational prospective study, enrolling consecutive IMID patients (pts) starting a target therapy. We principally focused on 3 cohorts: IBD, SpA and IBD-SpA. At baseline, we performed a test for serum cytokines and also collected intestinal biopsies, to stain for immune cell markers. Clinical intestinal and articular response (CR) was assessed at 4, 12 and 24 months. CR was defined using clinical scores: Patient Reported Ouctome-2 (PRO-2) for UC and CD, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score-C-Reactive Protein (ASDAS-CRP) for SpA Results We enrolled 134 pts (59 IBD, 75 SpA). All the SpA pts were seronegative with prevalent peripheric articular involvement. In the IBD cohort, 48% of the pts were naïve to advanced therapies, while the remaining part had been exposed to biologics. 34% pts were on concomitant steroid therapy at baseline. At baseline, we found lower serum levels of IL-6, IL-12/23, IL-7, IL-10, IL-33, IL-35 and IL-37 in IBD pts compared to SpA pts and that levels presented a direct or inverse correlation with the clinical scores (figure). In the IBD-SpA group, compared to the IBD group, we found higher levels of IL-6(p=0.001), sTREM1(p=0.027), IL10(p=0.002) and IL-37(p=0.016). According to PRO-2, 70% of pts were in steroid-free clinical remission at 12 months, and 81.8% at 24 months. Considering CR at 12 months, statistically significant differences were found in the groups of responders versus no responders. In the IBD cohort we found that 100% of responders, had low levels of IL-8(<8.6 pg/mL) and low CD117 cell count in intestinal tissue at baseline; besides, 80% of responders had high CD20 count in intestinal tissue at baseline. Kaplan-Meier curves for achieving CR at 24 months, in the entire cohort of pts, showed no statistically significant differences stratifying pts on demographic characteristics and type of disease Conclusion In IBD pts, we found results which could suggest a different systemic inflammation signature between IBD and SpA pts and the presence of possible biomarkers which, if confirmed, could help the physician in the early and non-invasive identification of the disease phenotype at diagnosis and response to therapies

CLINICAL CHARACTERISTICS AND SERUM CONCENTRATIONS OF SOME T-HELPER 2-DERIVED CYTOKINES IN PATIENTS WITH GENERALIZED ERYTHEMA MULTIFORME

Objective: To describe the clinical characteristics of patients with erythema multiforme (EM) presenting with generalized skin lesions and to investigate the serum concentrations of certain T-helper 2 (Th2) cytokines in these patients, exploring their correlation with specific clinical features. Subjects and Methods: This cross-sectional descriptive study included 33 patients diagnosed with EM featuring generalized skin lesions at the National Hospital of Dermatology and Venereology from April 2017 to August 2019. Additionally, 32 healthy controls (HCs) participated as the control group. Clinical examinations, medical history interviews, and serum sample collections were conducted for all subjects. The fluorescence covalent microbead immunosorbent assay technique was used to detect multiple cytokines simultaneously: IL-4, IL-5, and IL-13. The Mann-Whitney U test compared the serum cytokine levels between the two groups, with statistical significance set as p<0.05. Pearson's test was applied to evaluate the correlation between two quantitative variables. Results: The mean age of EM patients with generalized lesions was 42.2 years; 30.3% were male, and 69.7% were female. Twenty-two patients (66.7%) had an illness duration of less than one week—a history of medication use before illness onset was reported by 60.6% of patients. Only 15.2% of patients had mucosal lesions. In the EM group, serum levels of IL-4 and IL-5 were 1.55±4.35 pg/ml and 7.12±18.91 pg/ml, respectively, which were lower than those in the HCs group (9.15±10.17 pg/ml and 21.38±20.85 pg/ml, respectively), p<0.001. Serum IL-13 levels were identical in both groups (1.48 pg/ml). No correlation was found between serum IL-4 levels and age (r=0.08; p>0.05), nor between serum IL-5 levels and age (r=-0.055; p>0.05). Conclusion: Th2 cytokine levels in the EM group with generalized skin lesions were lower compared to the HCs group, with no correlation between these cytokine levels and age. Th2 is likely not an important factor in the pathogenesis of generalized EM. Received: 16 May 2023Revised: 24 June 2023Accepted: 22 July 2023

Peripheral blood age-sensitive immune markers in multiple sclerosis: relation to sex, cytomegalovirus status, and treatment.

Immunosenescence is accelerated by chronic infectious and autoimmune diseases and could contribute to the pathobiology of multiple sclerosis (MS). How MS and disease-modifying therapies (DMTs) impact age-sensitive immune biomarkers is only partially understood. We analyzed 771 serum samples from 147 healthy controls and 289 people with MS (PwMS) by multiplex immunoassays. We determined cytomegalovirus (CMV) serostatus and collected retrospective clinical information. We performed unsupervised and multivariable analyses. Unsupervised analyses revealed that MS immune profile was characterized by low relative levels of anti-inflammatory/neuroprotective factors IL-4, IL-10, TNF, and β-NGF but high levels of growth factors EGF and bFGF. Serum levels of IL-4, β-NGF, IL-27, BDNF, and leptin were significantly influenced by sex and/or CMV status. IL-4 and β-NGF levels were lower in untreated PwMS compared to controls, while EGF and bFGF levels were influenced by age and markedly elevated in PwMS in multivariable analysis. Samples from treated PwMS, but not untreated PwMS, showed lower levels of BDNF and TNF than controls. Initiation of high efficacy DMTs, but not low efficacy DMTs, was associated with reduced levels of bFGF and EGF. Samples associated with distinct DMTs exhibited specific profiles for age-sensitive immune markers. Finally, lower levels of IL-6, TNF, IL-10, and β-NGF were observed at baseline in PwMS who subsequently experienced clinical failure after DMTs initiation. Age, sex, CMV status, and specific DMTs significantly influence levels of age-sensitive immune biomarkers associated with MS and must be considered when investigating inflammation-related biomarkers. This work was supported by a Grant for Multiple Sclerosis Innovation by Merck KGaA (ID: 10.12039/100009945).

Characterization of serum and brain cytokine levels following prolonged binge-like methamphetamine self-administration and cued methamphetamine seeking.

Methamphetamine (METH) use is associated with peripheral and brain inflammation that can contribute to METH-associated toxicity and heightened cue reactivity. However, the persistence of these phenomena, especially with regards to changes in brain proinflammatory cytokine levels, is not yet clear. In this study, we determined the effects of repeated binge-like METH self-administration (96-h/week for 3weeks) followed by cued drug seeking for up to 60days into abstinence in male and female rats. Serum cytokine levels were assessed prior to cued drug seeking tests on days 21 and 60 of abstinence, and cytokine levels in the prefrontal cortex (PFC) and dorsal striatum (DStr) were assessed on the day following that last cued seeking test. We observed robust levels of METH intake in both sexes as well as a gradual increase in magnitude of METH seeking across abstinence that did not differ between sexes. Magnitude of METH seeking on days 10 and 60 were positively correlated with prior total drug intake. Sex- and region-dependent changes in various chemokines and interleukins were observed in the PFC and DStr, as were sex- and time-dependent changes in serum cytokine levels, with the largest number of cytokines altered on day 60 in male animals. Serum levels of IL-6 were positively correlated with brain levels of this cytokine, but serum levels of this and other cytokines did not correlate with the magnitude of METH seeking. These findings suggest that binge-like METH intake produces persistent yet divergent central and peripheral immune responses that extend well into abstinence.

Cross-Sectional Analysis of IL-6, TNF-α, Adiponectin, Leptin, and Klotho Serum Levels in Relation to BMI Among Overweight and Obese Children Aged 10-14 in La Rioja, Spain.

Childhood obesity is a major public health concern, being linked to an increased risk of metabolic disorders and cardiovascular disease. Even in childhood, obesity is associated with systemic low-grade inflammation, which is a critical factor in the development of atherosclerosis and a predictor of cardiovascular morbidity and mortality. To describe the prevalence of obesity and examine the relationship between IL-6, TNF-α, adiponectin, leptin, the leptin/adiponectin (L/A) ratio, and Klotho levels with BMI in children. This cross-sectional study included children aged 10-14 years from La Rioja, Spain. Participants were selected based on BMI criteria for overweight (85th-95th percentiles) and obesity (>95th percentile). Socio-demographic and anthropometric data and blood samples were collected and analyzed for IL-6, TNF-α, adiponectin, leptin, and Klotho. A total of 340 participants were included, with 276 (81.2%) classified as normal weight and 64 (18.8%) as overweight or obese. Mean age was similar between groups (p = 0.40). Obesity was more prevalent in males (59.4%, p = 0.048). Obese participants had higher mean birth weight (p = 0.003), current height (p = 0.04), BMI (p < 0.0001), and abdominal circumference (p < 0.0001). BMI correlated positively with leptin (r = 0.54, p = 0.0008) and the L/A ratio (r = 0.40, p = 0.025), showing sex-specific differences. This study underscores leptin and the L/A ratio as potential biomarkers of metabolic dysregulation in childhood obesity, particularly in females. Longitudinal studies are needed to confirm these findings and assess the clinical utility of these biomarkers in pediatric obesity management.

Assessment of inflammatory markers in Acne vulgaris patients: serum IL-17, IL22, and IL-10

One of the four main factors in the pathophysiology of acne vulgaris (AV) is inflammation, which may be a primary or secondary process caused by Propionibacterium acnes. To counteract inflammatory mediators, the immune system possesses a variety of anti-inflammatory mechanisms. The data supporting the early involvement of the inflammatory pathway in the etiology of AV, a chronic, complex, inflammatory skin condition, has become more clear. This cell line's activators, Th17 cells, and the cytokines that follow are all probably important in initiating and maintaining the disease. The aim of this study is to determine the degree to which acne vulgaris is influenced by the interleukins IL-10, IL-17, and IL-22. Individualized patients in our study, sex-matched controls were included, and there were 42 male and 58 female AV patients, aged 12 to 30. An enzyme-linked immunosorbent assay (ELISA) was used to measure the serum levels of IL-10, IL-17, and IL-22. The levels were then connected with the severity of acne. In cases, the serum levels of IL-10, IL-17, and IL-22 were 0.34±0.080, 0.13, 0.14±0.0035, 0.136-0.233, and 0.24±0.0142, 0.126-0.243 pg/ml, respectively, while in controls, they were 0.13±0.028, 0.10±0.0085, 0.14±0.0035, 0.117-0.126, and 0.22±0.0089, 0.114-0.127 pg/ml. For IL-10 and IL-17, there was a substantial difference in levels between patients and controls; however, for IL-22, the difference was negligible. The levels of IL-10 and IL-17 showed an extremely strong positive connection. This study came to the conclusion that IL-10 and IL-17 are important effectors in the pathophysiology of AV. In acne lesions, Th17 cells activated by IL-22 are probably the main source of IL-37.

Frailty and osteoporotic fractures represent mutual risks for each other with common physiological backgrounds

Abstract Frailty and osteoporosis are known to exacerbate each other. However, limited research is available on the shared pathophysiological factors contributing to osteoporotic fractures and frailty. This study aims to identify common factors associated with both the current frailty and the occurrence of incident vertebral fractures. A total of 912 postmenopausal Japanese women, 63.9 ± 10.0 years of age (mean ± SD), were included in the present study. Each participant’s baseline frailty status was assessed using a questionnaire about the five following items: Fatigue, Resistance, Ambulation, Inactivity, and Weight Loss. A score of 3 or above indicated the prevalence of frailty. The participants were then followed up for an average of 10.5 ± 7.5 years, during which 202 patients suffered incident vertebral fractures. The Cox proportional hazards model for incident vertebral fracture revealed that lumbar bone mineral density (HR 0.753, P&amp;lt;.001), adiponectin (HR 1.025, P=.021), Log IL-6 (HR 1.227, P=.029), prevalent vertebral fracture (HR 2.124, P&amp;lt;.001), and frailty status (HR 1.355, P=.002) were independent predictors of incident vertebral fractures. The factors associated with frailty status at baseline were assessed using logistic regression analysis, revealing that adiponectin (OR 1.063, P&amp;lt;.001), Log IL-6 (OR 2.94, P&amp;lt;.001), and prevalent vertebral fractures (OR 2.816, P&amp;lt;.001) were significantly associated with current frailty. Biochemical factors such as IL-6 and adiponectin were commonly associated with vertebral fractures and frailty. Additionally, frailty status was identified as an independent risk factor for vertebral fractures, while prevalent vertebral fractures were significantly associated with frailty. These findings clearly indicate that frailty and osteoporotic fractures represent mutual risks for each other, with serum levels of adiponectin and IL-6 serving as common physiological backgrounds.

Serum interleukin-6 and associated nociceptive parameters following subcutaneous infiltration of lidocaine alone, tramadol alone, and their combination in red Sokoto goat undergoing rumenotomy

The clinical practice of combining one or more drugs is gaining attention for enhancing efficacy, leading to quicker onset of action, longer duration of effect and minimising side effects. Previous studies showed that combining lignocaine and tramadol in an epidural injection significantly extended the duration of analgesia produced when compared to the use of lignocaine alone. The significance of this study is aiming toward improved pain management during surgery, especially in goats. In this study, the analgesic effects of subcutaneously administered lignocaine alone (7 mgkg-1), tramadol alone (3 mgkg-1), and their respective combination of 3.5 and 15 mgkg-1 on pain in goats undergoing rumenotomy were compared. The experiment was carried out on fifteen healthy (N=15) Red Sokoto goats. Blood was drawn from the jugular vein at seven distinct time intervals during the course of the experiment (0, 1, 2, 3, 4, 5, 6 and 7 hours) and serum was extracted. The severity of pain was ascertained by measuring serum level of IL-6 and the nociceptive response to a pain stimulus using a clinical algometer. This study revealed that the combination of lidocaine (03.78 minutes) and tramadol (3.68 minutes) has a quicker onset of action (2.01±0.42 minutes) and a more extended duration of activity (79.5 minutes) when compared to lidocaine (60 minutes) and tramadol (55.75 minutes) administered separately. There was no significant difference (P&gt;0.05) in serum IL-6 before and after the administration of lidocaine, tramadol, or their combination. This study has demonstrated that the lidocaine-tramadol combination at respective doses of 3.5 and 1.5 mgkg-1 has a quicker onset and longer duration of activity when subcutaneously administered at the surgical site, in comparison with lidocaine alone and tramadol alone at respective doses of 7 and 3 mgkg-1. However, there was no remarkable difference in the serum pain biomarker (IL-6) among the three different treatments. Subcutaneous infiltration of the combination of lidocaine at 3.5 mgkg-1 with tramadol at 1.5 mgkg-1 via the inverted L block technique can be employed as an alternative to conventional lidocaine alone to achieve loco-regional analgesia for a more prolonged duration in goats to conduct laparotomy. Clinically, this drug combination could be useful in surgeries requiring extended regional anaesthesia, reducing the need for repeated dosing, hence improving animal welfare.

Systemic regulatory factors of angiogenesis in multiple uterine myoma

Uterine leiomyomas (UL) are benign uterine tumors. Hypertrophic increase in muscle mass in LM is accompanied by development of vascular networks, which are regulated by the balance of pro-angiogenic factors, e.g., VEGF-A. Moreover, a number of inflammatory molecules exert pro-angiogenic effects, especially, IL-1β, IL-8, etc. The spectrum of their activity may overlap, being regulated by other cytokines. The aim of our work was to assess serum concentrations of cytokines actively involved in vascular network growth in the patients with multiple uterine fibroids, as compared with data obtained in conditionally healthy women. The survey included 178 females: 89 women (23-60 years old) with uterine fibroids, and 89 conditionally healthy age-matched women (22-61 years old). The levels of TNFα, IL-1β, IL-4, IL-6, IL-8, IL-10 and VEGF-A were detected by ELISA technique (Vector-Best, Russia). Statistical analysis was carried out using the IBM SPSS Statistics 23 (USA). Serum levels of IL-6, TNF and IL-8, were higher among patients compared with healthy women. The dependence of VEGF level on the number of myoma nodes has been established: VEGF serum level was higher in patients with multiple tumor nodes. In healthy women, an increase in TNFα level showed direct correlation with higher serum level of IL-6. Correlation with VEGF level was weakly negative. In leiomyoma, these relationships persist for IL-6, IL-8, VEGF levels. The obtained data are of practical importance not only as potential prognostic criteria for development of the uterine myoma at preclinical stage, but also as additional laboratory indexes for differential diagnostics, in particular when discerning uterine leiomyoma, the most common benign myomatous tumor of uterus, from malignant uterine leiomyosarcomas.

Clinical values of serum platelet-activating factor in hypertensive disorders complicating pregnancy.

Serum platelet-activating factor (PAF) was proven to be associated with gestational hypertension. However, the predictive value of serum PAF at early pregnancy for the occurrence and outcomes of hypertensive disorders complicating pregnancy (HDCP) remained unclear. The demographic and clinical characteristics of patients were compared among the different subgroups. The serum PAF level was determined using an enzyme-linked immunosorbent assay. The predictive value of serum PAF for the occurrence and outcomes of HDCP was evaluated using receiver operating characteristic curve analysis. The correlation of serum PAF with blood pressure was assessed using Spearman analysis. Both systolic blood pressure and diastolic blood pressure were significantly higher in HDCP patients, as well as the serum levels of TNF-α and IL-1β at diagnosis/enrollment, while serum levels of IL-10 showed the opposite trend. Serum PAF levels were significantly higher in patients with HDCP compared to normal pregnant women. Furthermore, serum PAF levels were higher in HDCP patients with mild preeclampsia compared to those with gestational hypertension and even more elevated in HDCP patients with severe preeclampsia at the early pregnancy stage and at diagnosis. In HDCP patients, increased serum PAF levels at early pregnancy and at diagnosis were associated with poor outcomes. Additionally, serum PAF levels could predict the occurrence of HDCP and poor outcomes. Serum PAF from HDCP patients at both the early pregnancy and diagnosis stages could effectively predict the occurrence and outcome of HDCP.

Olive oil and castor oil-based self-nanoemulsifying drug delivery system of flurbiprofen can relieve peripheral pain and inflammation through reduction of oxidative stress and inflammatory biomarkers: a comprehensive formulation and pharmacological insights.

Flurbiprofen (FBP) is poorly water-soluble BCS class II drug with anti-inflammatory and analgesic effects, used to treat arthritis and degenerative joint diseases. This study was aimed to develop SNEDDS loaded with FBP. Six SNEDDS using two oils olive oil (F1OLV, F2OLV, F3OLV) and castor oil (F4CAS, F5CAS, F6CAS) with three different Smix ratios consisting of Tween 20 and PEG 400 (1:1, 1:2, 2:1) were prepared and characterized. Compatibility between FBP and polymers was investigated using FTIR. SNEDDS were characterized for physicochemical attributes. Two optimized formulations were investigated at 10mg/kg dose given orally in Wistar rats for analgesic activity by hot plate and tail flick methods, and anti-inflammatory activity by carrageenan induced paw edema method. Anti-inflammatory activity was further explored by motor coordination and motility by Rota rod and cage activity tests. Following anesthesia blood samples were collected before dissection to measure inflammatory mediators and oxidative stress markers. Sciatica nerves and hind paws of rats were also removed for histopathological evaluation.FTIR studies revealed compatibility of FBP with other components. Droplet size of F1OLV, F2OLV, F3OLV was 128.5 ± 0.7 nm, 202.5 ± 1.3 nm, and 541.5 ± 1.7 nm, whereas it was 142.5 ± 1.1 nm, 215.4 ± 1.2 nm and 349.9 ± 1.8 nm for F4CAS, F5CAS, F6CAS. %EE of F1OLV, F2OLV, F3OLV was found 85 ± 4.89%-91 ± 4.67%, whereas the %EE F4CAS, F5CAS, F6CAS was 84 ± 4.15%-90 ± 4.21%. DSC curves of F1OLVand F4CASrevealed amorphous nature of the FBP. SEM showed spherical shape of globules. % of drug released in the pH medium 1.2 for plain FBP, F1OLVand F4CASwas 25%, 59% and 57%. % drug released in the pH 6.8 for plain FBP, F1OLVand F4CASwas 59%, 85% and 83%. Oral administration of FBP-loaded SNEDDS (F1OLV and F4CAS) significantly decreased paw diameter and enhanced motor coordination in rats when compared to the disease control group. This was linked to the ability of FBP to reduce inflammation and oxidative stress, with histological studies indicating decreased tissue damage in SNEDDS treated groups, implying the possibility of tissue recovery. Administration of both formulations started to demonstrate analgesic and anti-inflammatory effects after one hour of administration. In addition to anti-inflammatory effect, both formulations improved motor coordination, motility, and reduced infiltration of inflammatory cells in the inflamed paws. The anti-inflammatory and analgesic activities were attributed to decreased serum levels of IL-6 and TNF-α, increased activity of SOD and reduced nitrite content in sciatic nerves. Histopathological evaluation revealed reduced vascularity, inflammation and synovial hyperplasia. The overall findings suggest that the FBP loaded SNEDDS can be used as carriers for improved delivery of FBP which can effectively be used to cure pain and inflammation.

Role of IL-6, TNF-α and VCAM-1 as predictors of renal impairment in patients with spontaneous bacterial peritonitis.

Multiple mechanisms may contribute to the occurrence of renal impairment (RI) in patients with spontaneous bacterial peritonitis (SBP). One such mechanism is systemic inflammatory response syndrome, which involves the release of pro-inflammatory cytokines (tumour necrosis factor [TNF]-α, interleukin [IL]-6 and vascular cell adhesion molecule [VCAM]-1). The goal of this research was to evaluate the role of IL-6, TNF-α and VCAM-1 as potential predictors of RI and mortality in cirrhotic patients with SBP. This study included 90 cirrhotic patients with SBP, divided into two equal groups: group A was patients without RI and group B was patients with RI. Based on mortality outcomes, the patients were further categorized into group 1 (recovery, n=70) and group 2 (death, n=20). TNF-α, IL-6 and VCAM-1 serum levels were measured using enzyme-linked immunosorbent assay. RI occurred in 50% (45/90) of the study population. Among the 90 patients, 10 (11.1%) had elevated IL-6 levels, 8 (8.9%) had elevated TNF-α levels and 6 (6.7%) had elevated VCAM-1 levels. There were no significant variations in cytokine levels between groups A and B. With an area under the curve of 0.5, the three cytokines showed comparable sensitivity and specificity as predictors of RI. The use of TNF-α, IL-6 and VCAM-1 as predictive markers for RI and mortality in SBP patients is not recommended, as these biomarkers demonstrated limited diagnostic value.

Chronic artificial light exposure in daytime and reversed light: Dark cycle inhibit anti-apoptotic cytokines and defect Bcl-2 in peripheral lymphoid tissues during acute systemic inflammatory response to lipopolysaccharide.

The disturbed light: dark (LD) cycle has been associated with critical complications, including obesity, diabetes and cancer. In the present study, we investigated the chronic effects of artificial light at daytime (AL) and light at night (RAL) after intraperitoneal (i.p.) injection of saline and 0.5mg/kg lipopolysaccharide (LPS) in male Wistar rats. Liver and kidney parameters, fasting blood glucose (FBG), melatonin level, immunohistochemical examinations of B-cell lymphoma-2 (Bcl-2) in spleen and mesenteric lymph and serum antiapoptotic cytokines [interleukin (IL-) 2, 7 and 1]. After 16weeks of a daily disturbed LD cycle, RAL increased body weight, upgraded FBG and altered liver and kidney functions with surprisingly increased daytime plasma melatonin. AL+LPS and RAL+LPS rats suffered significantly higher oxidative-nitrosative stress compared to NL+LPS. Oxidative-nitrosative stress was associated with multi-organ inflammation in hepatic, renal, pancreatic, splenic and mesenteric lymph node tissues due to LPS-induced endotoxemia. Anti-apoptotic Bcl-2 activity in peripheral lymphoid organs (spleen and mesenteric lymph node) was lowered due to AL and RAL regimens. At the same pattern, lowering of antiapoptotic serum levels of IL-2, IL-7 and IL-15 indicate alteration of cell cycle and the shifted ability of cells to undergo apoptosis due to abnormal light pollution. Here, the increased lymphocyte apoptosis in lymphoid tissues due to disturbed LD cycle defects the host defense, dysregulates the inflammatory immune response and dysregulates the immune tolerance during acute systemic inflammation due to LPS.