Plasma Interleukin-6 Research Articles

Effect of specific immunotherapy on plasma interleukin 13 and 8 levels in patients with allergic rhinitis

Effect of specific immunotherapy on plasma interleukin 13 and 8 levels in patients with allergic rhinitis

Effect of specific immunotherapy on plasma interleukin 13 and 8 levels in patients with allergic rhinitis

Effect of specific immunotherapy on plasma interleukin 13 and 8 levels in patients with allergic rhinitis

EFFECTS OF AEROBIC EXERCISE ON INFLAMMATION MARKERS AMONG OVERWEIGHT WOMEN

The purpose of this research was to examine the effects of 12 weeks of aerobic exercise on inflammation markers among overweight women. A sample of 20 overweight females between the ages of 18 to 24 years were recruited from the Women's University of Azad Jammu & Kashmir Bagh. Plasma interleukin-6 (IL-6), C-reactive protein (CRP), and anthropometric parameters were checked before and after 12 weeks of aerobic training (AT). Paired sample T-test was used for changes over time. The study revealed a significant effect of aerobic exercise on participant’s CRP (4.98 ± 1.65 vs 3.74 ± .61 P = 0.003) and IL-6 (8.41 ± 4.02 vs 5.22 ± 2.93 P = 0.001) levels. The study also found significant positive effects of long-term aerobic training on weight and BMI. Aerobic training significantly improves CRP and IL-6 and anthropometric measurements such as waist-hip ratio (WHR) weight and body mass index (BMI). The training protocol used can be used as a good tool for the reduction of weight and maintenance of good health, especially for females. Being overweight should not be considered trivial and needs special consideration and awareness for the serious consequences associated with obesity and overweight.

Haemocytometric profile and plasma levels of selected cytokines in patients at various stages of cervical cancer

Introduction and aim. Reports have shown that there is alteration in haematological and inflammatory processes in patients with cervical cancer. However, there is the dearth of information on the pattern of alteration in Nigerian patients with cervical cancer at various stages of the disease. Therefore, haemocytometric profile and plasma levels of interleukin-6 (IL-6) and IL-12 were determined in Nigerian patients with cervical cancer at various stages of the disease. Material and methods. Eighty-nine adults consisting of 49 patients with cervical cancer and 40 apparently healthy controls were enrolled into this study. Haemocytometric profile was determined using automated haematology analyzer while the plasma levels of interleukin-6 (IL-6) and IL-12 were determined using ELISA. Results. Of the participants with cervical cancer, 6.12%, 24.49%, 53.06% and 16.33% were in stages I, II, III and IV respectively. The mean plasma IL-6 level was significantly higher in patients at stage IV of the cancer compared with those in stages I, II and III. No significant differences were observed in the mean plasma IL-12 level, and the haemocytometric profile when patients in different stages of the cancer were compared with one another. Plasma IL-6 had significant positive correlation with the lymphocytes count and cancer stage but had significant negative correlation with packed cell volume (PCV), haemoglobin and total white blood cells count (WBC) in patients with cervical cancer. Conclusion. Interleukin-6 appears to play an important role in the progression of cervical cancer and could be involved in cervical cancer-associated alteration in haemocytometric profile.

Plasma interleukin 6 as an outcome predictor of traumatic brain injury patients.

Traumatic brain injury is one of the leading causes of death and disability in young adults. Previous studies have suggested that neuroinflammatory process involves the overexpression of interleukin 6 (IL-6); however, data on the predictive ability of IL-6 is limited and conflicting in traumatic head injury patients. The aim of this study was to assess the ability of plasma IL-6 as a predictor of outcome in head injury patients. A cross-sectional study was conducted between June and December 2020 among traumatic head injury patients admitted to Dr. Zainoel Abidin Hospital, Banda Aceh, Indonesia. Demographic, clinical data, and IL-6 level were collected and measured on admission. The outcome was assessed by the Glasgow outcome scale extended (GOSE) in the first- and third-month of post-injury. A total of 50 traumatic brain injury patients were recruited of which 54% were male, 64% had mild head injury, 82% had leukocytosis, and 60% had non-bleeding head CT scan. The mean of IL-6 level was 79.32 pg/mL while the GOSE scores ranged from 1 (death) to 8 (upper good recovery). Early IL-6 level (<24 hours post-injury) was significantly correlated with worse outcome in traumatic head injury, though the correlation strength was moderate (p<0.001; r=-0.42). As a predictor, IL-6 yielded the area under curve (AUC) value of 93.5% (p<0.001) and a cut-off point of 46.33 pg/mL. The sensitivity and specificity of this predictor were 87.5% and 95.24%, respectively. In conclusion, early IL-6 level can be used as a predictor for traumatic head injury. Nevertheless, further multi-center study with a bigger sample size is needed to confirm this finding.

Pulmonary Fibrosis with Increasing of Interleukin-6 in Sprague Dawley Rats with Metabolic Syndrome

Background: Pulmonary fibrosis is the result of chronic inflammation causing decreased lung function. Severe lung damage and worsening respiratory symptoms can caused by metabolic syndrome. In metabolic syndrome, obesity, dyslipidemia, hypertension, and insulin occurs, also chronic inflammation and increased interleukin-6. Research on rats with high-fat high-fructose diet caused metabolic syndrome that triggered chronic inflammatory formed pulmonary fibrosis, which decreased lung function. The study result aim to increase awareness of pulmonary fibrosis due to chronic inflammation in metabolic syndrome. Methods: The study design was true experimental in vivo test, pre and post test control group, with male Sprague-Dawley rats aged 37 weeks. Comparing each of 10 in control and metabolic syndrome groups. Metabolic syndrome expressed by increase of weight, triglycerides, blood sugar, and low HDL. Pulmonary tissue fibrosis assessed with modified Aschroft score. Examination of plasma and tissue Interleukin-6 by ELISA, and the degree of tissue fibrosis by HE staining under a microscope. Different test with independent T-test and Mann-Whitney methods. Results: There were significant differences in plasma and tissue Interleukin-6 and degree of lung tissue fibrosis between control and metabolic syndrome groups with each p&lt;0.05. There is an increase of plasma Interleukin-6, tissue Interleukin-6, and also degree of lung tissue fibrosis on metabolic syndrom group than control group. Conclusion: There is an increase in the degree of pulmonary tissue fibrosis accompanied by an increase in plasma and tissue IL-6 in rats with metabolic syndrome.

Dissociation of blood interleukin spectrum in the patients with accelerated aging and diabetic retinopathy

Diabetic retinopathy is a common complication of diabetes mellitus, especially, in elderly persons, due to growth of this population in many countries. However, involvement of immune system in patients with diabetic retinopathy and into the aging process is not sufficiently covered in the research works. The aim of the present study was to evaluate the contents of systemic interleukins in the patients with diabetic retinopathy with accelerated versus physiological aging.We observed 240 patients aged 60-74 years with diabetic retinopathy and 115 age-matched patients without diabetic retinopathy under clinical conditions. The diagnosis of diabetic retinopathy was assessed in accordance with Clinical Guidelines of the All-Russian Association of Ophthalmologists “Diagnostics and Treatment of Diabetic Retinopathy and Diabetic Macular Edema”. The biological age of the subjects was determined instrumentally, by means of VaSera VS-1500 sphygmomanometer. The contents of interleukins in blood plasma was determined by ELISA technique using the “Protein contour” kit.It was established that the chronological (calendar) age of patients with diabetic retinopathy and without diabetic retinopathy was not significantly different (70.9±0.7 and 70.2±0.8 years old, respectively; p &gt; 0.05). However, the biological age in these groups differed significantly (75.7±1.1 and 72.3±1.0 years old, respectively; p &lt; 0.001), thus suggesting accelerated aging of patients suffering from diabetic retinopathy. Plasma concentrations of interleukins in patients with diabetic retinopathy with accelerated aging, when compared with physiologically aged patients with diabetic retinopathy revealed statistically significant differences for the most analyzed interleukins. A particularly pronounced increase of the blood plasma interleukins in patients with diabetic retinopathy and accelerated aging was revealed for IL-6 (25.7±1.8 pg/mL versus 4.2±0.5 pg/mL in physiologically aged patients with diabetic retinopathy (p &lt; 0.001). A significant increase of interleukin levels among patients with accelerated aging and diabetic retinopathy was found for IL-13 and IL-17. IL-13 contents in the patients with diabetic retinopathy and accelerated aging reached 2.2±0.3 pg/mL versus 0.7±0.2 pg/mL in physiologically aging patients with diabetic retinopathy (p &lt; 0.001). Respectively, the IL-17 levels were 19.8±0.6 pg/mL and 8.4±0.9 pg/mL. The mean concentration of IL-1b, IL-3 among patients with diabetic retinopathy and accelerated aging was also significantly increased. At the same time, in the blood plasma of the prematurely aged patients with diabetic retinopathy, we have revealed a statistically significant decrease of anti-inflammatory interleukins and, especially, IL-10 to 7.4±0.6 pg/mL versus 19.2±0.7 pg/mL (p &lt; 0.001). Therefore, IL-6, IL-8, IL-13, IL-17, IL-4, and IL-10 levels may be used as immunological predictors of accelerated aging in the patients with diabetic retinopathy.

TUMOR NECROSIS FACTOR-Α, INTERLUKIN-6, AND VISFATIN LEVELS IN OLDER PATIENTS WITH MALNUTRITION

Abstract Introduction Proinflammatory cytokine is associated with malnutrition status. Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were pro-inflammatory cytokines stimulated by nutritional deficiency. Visfatin is an adipokine with a strong correlation with inflammation. The relationships of TNF-α, IL-6 and visfatin are not consistent, and no study have investigated them in the older patients with malnutrition. Methods This prospective study included patients aged ≥ 75 years at the emergency department and all patients underwent Mini-Nutritional Assessment-Short Form (MNA-SF) and blood tests for fasting plasma TNF-α, IL-6 and visfatin levels. Results We enrolled 106 older patients with a mean age of 87.3 years, including 43 (40.5%) patients in at risk of malnutrition group (MNA-SF between 8 to 11), 24 (22.6%) patients in the malnutrition group (MNA-SF &amp;lt; 8), and 39 (36.7%) patients in normal group. Compared to the normal group, both at risk of malnutrition and malnutrition group had significantly lower Mini-Mental State Examination (MMSE). Furthermore, TNF-α was significantly higher in at risk of malnutrition group. In contrast, IL-6 was significantly higher in malnutrition group. Visfatin levels was not correlated to the malnutrition status. Both TNF-α and IL-6 negatively correlated with Barthel index and MMSE. Backward and stepwise multiple logistic regression analyses showed that the independent predictor for both at risk of malnutrition and malnutrition was MMSE. Conclusion The nutrition deficit status was correlated with proinflammatory cytokines, serum TNF-α and IL-6. The independent predictor of both at risk of malnutrition and malnutrition group was MMSE in older patients.

EAAS AND WHEY PROTEIN MAY IMPROVE PHYSICAL FUNCTION OF OLDER ADULTS INDEPENDENTLY OF GUT MICROBIOME

Abstract Essential amino acids (EAAs) and dietary proteins are major nutritional supplements that support the growth and activity of gut microbes, contributing to the wellbeing of their host. We hypothesized that daily ingestion of EAAs or whey proteins for twelve weeks would improve the gut microbiome of older adults and thereby have a positive impact on their physical functioning. The stool samples were collected from the 40 subjects before and after consuming EAAs or whey proteins for twelve weeks and subjected to Illumina based 16S rRNA gene sequencing. In both groups, the most abundant families in order of relative abundance included: Bacteroidaceae, Ruminococcaceae, Lachnospiraceae, Rikenellaceae, and Prevotellaceae, which indicated that these subjects were able to maintain a dominant consortium of microbes in their guts that have been associated with healthy aging. Individual gut microbiome samples analysis with nonmetric multidimensional space (NMDS) showed that each individual was associated with its unique microbiome. The key finding of this study was a significant reduction of plasma Interleukin-18 binding protein (IL-18) in EAAs vs whey group (p &amp;lt; 0.003). It is plausible that the reduced level of inflammatory IL-18 contributed to improved intestinal immunity. Moreover, the reduced inflammation might have resulted in better muscle performance in the EAAs group vs whey as evidenced by six-minute walking distance (EAAs 92.55 ± 4.16 ft vs whey 47.46 ± 4.99 ft, p&amp;lt; 0.0001) at the completion of study. Future studies will need to explore the role of EAAs on gut microbiome mediated reduction of immune inflammation on physical function and aging.

Altered expression of miR-125a and dysregulated cytokines in systemic lupus erythematosus: Unveiling diagnostic and prognostic markers.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder impacting multiple organs, influenced by genetic factors, especially those related to the immune system. However, there is a need for new biomarkers in SLE. MicroRNA-125a (miR-125a) levels are decreased in T cells, B cells, and dendritic cells of SLE patients. MiR-125a plays a regulatory role in controlling the levels of tumor necrosis factor-alpha (TNF-α) and interleukin 12 (IL-12), which are crucial pro-inflammatory cytokines in SLE pathogenesis. To assess the levels of miR-125a, IL-12, and TNF-α in SLE patients' plasma, evaluating their diagnostic and prognostic value. The study included 100 healthy individuals, 50 newly diagnosed (ND), and 50 SLE patients undergoing treatment. The patients were monitored for a duration of 24 wk to observe and record instances of relapses. MiR-125a expression was measured using real-time reverse transcription polymerase chain reaction, while ELISA kits were used to assess IL-12 and TNF-α production. The results showed significantly reduced miR-125a expression in SLE patients compared to healthy individuals, with the lowest levels in ND patients. TNF-α and IL-12 expression levels were significantly elevated in SLE patients, especially in the early stages of the disease. Receiver operating characteristic curve analyses, and Cox-Mantel Log-rank tests indicated miR-125a, TNF-α, and IL-12 as proper diagnostic biomarkers for SLE. A negative correlation was found between plasma miR-125a expression and IL-12/TNF-α levels in SLE patients. Decreased miR-125a levels may be involved in the development of SLE, while elevated levels of IL-12 and TNF-α contribute to immune dysregulation. These findings offer new diagnostic and prognostic markers for SLE. Moreover, the negative correlation observed suggests an interaction between miR-125a, TNF-α, and IL-12. Further research is necessary to uncover the underlying mechanisms that govern these relationships.

Ningmitai capsule improves the semen quality of male infertile with chronic prostatitis by antioxidant and anti-inflammatory

Aim: To observe the effects of Ningmitai capsule on semen parameters of infertile patients with chronic prostatitis (CP) and explore the mechanisms. Methods: A total of 43 patients diagnosed with CP were included in the study and administered Ningmitai capsules (4 capsules per dose) for a duration of 6 weeks. Subsequently, assessments were conducted on parameters including sperm concentration, forward progressive motility, total motility, oxidative and anti-oxidative indicators, as well as the concentration of interleukin-8 (IL-8) in seminal plasma before and after the treatment period. Results: Compared to pre-treatment, forward progressive motility and total motility of the semen increased significantly (37.15% ± 18.77% vs. 45.44% ± 19.08%, P &lt; 0.05 and 42.56% ± 21.22% vs. 51.64% ± 19.48%, P &lt; 0.05). And the expression of superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) increased significantly after treatment as well (11.36 μmol/L ± 3.28 μmol/L vs. 12.79 μmol/L ± 2.87 μmol/L, P &lt; 0.05 and 9.34 U/mL ± 3.22 U/mL vs. 11.21 U/mL ± 4.87 U/mL, P &lt; 0.05). In addition, the expression of malondialdehyde (MDA) and IL-8 decreased significantly after treatment (41.06 μmol/L ± 24.39 μmol/L vs. 32.17 μmol/L ± 15.04 μmol/L, P &lt; 0.05 and 79.69 ng/L ± 26.24 ng/L vs. 61.35 ng/L ± 23.41 ng/L, P &lt; 0.05). No significant difference in sperm concentration and sperm DNA fragmentation index was observed after the treatment (P &gt; 0.05). Conclusions: Ningmitai capsule can enhance the antioxidant capacity and down-regulate the expression of cytokines in the semen, thereby improving the semen parameters of infertile patients with CP.

Interleukin-4 during post-exercise recovery negatively correlates with the production of phagocyte-generated oxidants.

Exhaustive run induced a biphasic oxidative response of circulating phagocytes in 16 amateur sportsmen. The first phase involved an increment just after exercise of enhanced whole blood chemiluminescence normalized per phagocyte count, whereas in the second phase a decrement from 1h post-exercise and ongoing till 24h. We tested whether plasma Interleukin IL-4, IL-8, IL-10 and Tumor Necrosis Factor α concentrations change in response to exhaustive run and whether there are associations between their levels and delta resting. Moreover, IL-8 and IL-10 significantly increased immediately post-exercise and after 1h, but later normalized. Tumor necrosis factor α rose by 1.1-times only just after exercise. However, none of these cytokines showed any correlation with the investigated chemiluminescence. Exercise did not alter plasma concentrations of IL-4. However, pre-exercise IL-4 negatively correlated with measured luminescence just after exercise (ρ = -0.54, p < 0.05), and also tended to be negatively associated with decrements of the second phase at 1h post-exercise ρ = -0.45, p = 0.08. It is suggested that plasma IL-4, by a negative association with blood phagocytes oxidants production, could be involved in the maintenance of proper balance between oxidants and anti-oxidants during strenuous exercise and post-exercise recovery.

The biology of hope: Inflammatory and neuroendocrine profiles in ovarian cancer patients

IntroductionAlthough the concept of hope is highly relevant for cancer patients, little is known about its association with cancer-relevant biomarkers. Here we examined how hope was related to diurnal cortisol and interleukin-6 (IL-6), a pro-inflammatory cytokine previously associated with tumor biology and survival in ovarian cancer. Secondly, we examined whether hope and hopelessness are distinctly associated with these biomarkers. MethodParticipants were 292 high-grade ovarian cancer patients who completed surveys and provided saliva samples 4x/daily for 3 days pre-surgery to assess diurnal cortisol. Blood (pre-surgery) and ascites were assessed for IL-6. Hope and hopelessness were assessed using standardized survey items from established scales (Center for Epidemiological Studies Depression Scale; Profile of Mood States, Functional Assessment of Cancer Therapy). Two hopeless items were z-scored and combined into a composite for analysis. Regression models related these variables to nocturnal cortisol, cortisol slope, plasma and ascites IL-6, adjusting for cancer stage, BMI, age, and depression. ResultsGreater hope was significantly related to a steeper cortisol slope, β = −0.193, p = 0.046, and lower night cortisol, β = −0.227, p = 0.018, plasma IL-6, β = −0.142, p = 0.033, and ascites IL-6, β = −0.290, p = 0.002. Secondary analyses including both hope and hopelessness showed similar patterns, with distinct relationships of hope with significantly lower nocturnal cortisol β = −0.233,p = 0.017 and ascites IL-6, β = −0.282,p = 0.003, and between hopelessness and a flatter cortisol slope, β = 0.211, p = 0.031. ConclusionsThese data suggest a biological signature of hope associated with less inflammation and more normalized diurnal cortisol in ovarian cancer. These findings have potential clinical utility but need replication with more diverse samples and validated assessments of hope.

Regulatory mechanism of the six-method massage antipyretic process on lipopolysaccharide-induced fever in juvenile rabbits: A targeted metabolomics approach

ObjectiveTo investigate the mechanism of the six-method massage antipyretic process (SMAP) and its influence on the body's metabolic state. MethodsThe random number table method was used to divide 24 New Zealand 2-month-old rabbits with qualified basal body temperature into a control group, model group and massage group (n = 8 per group). The model group and massage groups were injected with 0.5 μg/ml lipopolysaccharide (1 ml/kg) into the auricular vein, and the control group was injected with the same amount of normal saline at the same temperature. One hour after modelling, the massage group was given SMAP (opening Tianmen, pushing Kangong, rubbing Taiyang, rubbing Erhougaogu, clearing the Tianheshui and pushing the spine). The change of anal temperature 5 h after moulding was recorded to clarify the antipyretic effect. ResultsAfter modelling, the rectal temperature of the juvenile rabbits in the three groups increased. The rectal temperature of the model group was higher than that of the control group 5 h after modelling, and the rectal temperature of the massage group was lower than that of the model group (P < 0.05). The antipyretic mechanism is related to the regulation of the synthesis of phenylalanine, tyrosine and tryptophan, as well as the pentose phosphate pathway. Compared with the model group, the plasma interleukin (IL)-1, IL-6, interferon-gamma, toll-like receptor 4, nuclear factor κB, the mechanistic target of rapamycin complex 1, indoleamine 2,3-dioxygenase 1, aryl hydrocarbon receptor, liver aspartate transaminase (AST), alanine transaminase (ALT) and l-glutamate dehydrogenase (L-GLDH) expression in the massage group were significantly decreased (P < 0.05). Compared with the model group, the massage group had significantly reduced AST, ALT and L-GLDH expression in plasma (P < 0.05). ConclusionThe mechanism of SMAP therapy is related to regulating the expression of peripheral inflammatory factors and metabolic pathways.

Effects of combined aerobic exercise and diet on cardiometabolic health in patients with obesity and type 2 diabetes: a systematic review and meta-analysis

BackgroundLifestyle modifications involving diet and exercise are recommended for patients diagnosed with obesity and type 2 diabetes mellitus (T2DM). The purpose of this review was to systematically evaluate the effects of combined aerobic exercise and diet (AEDT) on various cardiometabolic health-related indicators among individuals with obesity and T2DM.MethodologyA comprehensive search of the PubMed/Medline, Web of Science, Scopus, Science Direct, Cochrane, and Google Scholar databases was conducted for this meta-analysis. The Cochrane risk of bias tool was used to evaluate eligible studies, and the GRADE tool was used to rate the certainty of evidence. A random-effects model for continuous variables was used, and the results were presented as mean differences or standardised mean differences with 95% confidence intervals.ResultsA total of 16,129 studies were retrieved; 20 studies were included, and data were extracted from 1,192 participants. The findings revealed significant improvements in body mass index, body weight, waist circumference, systolic blood pressure, diastolic blood pressure, total cholesterol, triglycerides, fasting blood glucose, fasting plasma insulin, glycated hemoglobin, leptin, interleukin-6, C-reactive protein, and adiponectin (p < 0.05) compared to the standard treatment (ST) group. No significant differences were observed between the AEDT and ST groups in fat mass, hip circumference, waist-to-hip ratio, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and tumor necrosis factor-alpha. The present findings are based on low- to moderate-quality evidence.ConclusionsAEDT may be a critical behavior for holistic cardiometabolic health-related benefits as a contemporary anti-obesity medication due to its significant positive impact on patients with obesity and T2DM. Nevertheless, further robust evidence is necessary to determine whether AEDT is an effective intervention for lowering cardiovascular and metabolic risk factors among individuals with obesity and T2DM.

Effect of Amino Acid Supplementation on Iron Regulation after Endurance Exercise

The purpose of this study was to determine the effects of pre-exercise amino acid (AA) supplementation on post-exercise iron regulation. Ten healthy males participated under two different sets of conditions in a randomized, double-blind, crossover design with a washout period of at least 21 days. Participants received either an AA supplement or placebo (PLA) for five consecutive days (4 g/dose, 3 doses/day). On the sixth day, participants ran on a treadmill for 60 min at 70% of maximal oxygen consumption (V˙O2max). Venous blood samples were collected before (baseline), immediately after, and 1 and 3 h after exercise. The serum hepcidin levels increased significantly 3 h post-exercise in both trials when compared to the baseline (p &lt; 0.001), but the levels were not different between trials. The plasma interleukin-6 (IL-6) level significantly increased immediately after exercise compared to the baseline (p &lt; 0.001) and was significantly higher in the AA trial than in the PLA trial (p = 0.014). Moreover, the exercise-induced increase in serum glycerol level was significantly higher in the AA trial (21.20 ± 3.98 mg/L) than in the PLA trial (17.28 ± 4.47 mg/L, p = 0.017). No significant differences were observed between the AA and PLA trials for serum iron, ferritin, and total ketone body levels (p &gt; 0.05). In conclusion, five days of AA supplementation augmented exercise-induced increases in IL-6 and glycerol in healthy males. However, it did not affect post-exercise iron status or regulation.

Brazilian green propolis prevent Alzheimer’s disease-like cognitive impairment induced by amyloid beta in mice

BackgroundThe increasing incidence of cognitive impairment has become a health problem in the aging society. Owing to its antioxidant and anti-inflammatory properties, Brazilian green propolis—derived from Baccharis dracunculifolia—is anticipated to possess anticognitive properties. However, the preventive effect of Brazilian green propolis on cognitive impairment remains unexplained. This study aimed to investigate the effect of Brazilian green propolis on cognitive impairment using a mouse model of Alzheimer’s disease (AD) induced by intracerebroventricular injection of amyloid beta (Aβ)25‒35.MethodsFive-week-old male Slc:ddY mice were randomly divided into five groups (n = 8). The groups were pretreated with vehicle and propolis at a dose of 100, 300 and 900 mg/kg body weight for 8 days, then AD-like phenotypes were induced by intracerebroventricular (ICV) injection of Aβ25‒35. A sham operation group was set as the control. Memory and learning ability were measured at 7 to 8 days after ICV injection. Gene expression and histological studies were performed at the endpoint of the study.ResultsIn a passive avoidance test, the administration of Brazilian green propolis prevented the impairment of learning and memory function. Furthermore, comprehensive gene expression analysis in the hippocampus and forebrain cortex revealed that Brazilian green propolis suppressed Aβ25–35-induced inflammatory and immune responses. In particular, Brazilian green propolis prevented alterations in gene expressions of microglial and astrocytic markers such as Trem2 and Lcn2 induced by Aβ25‒35 injection, suggesting the suppression of excessive activation of glial cells in the brain. In addition, Brazilian green propolis suppressed the elevation of plasma interleukin (IL)-6 levels induced by Aβ25‒35 injection.ConclusionsThe results suggest that the prophylactic administration of Brazilian green propolis has a preventive effect against AD by suppressing excessive inflammation and immune response in glial cells. To our knowledge, this study is the first to demonstrate that Brazilian green propolis may inhibit the hyperactivation of microglia and astrocytes as a mechanism of action to prevent AD. Thus, it is a promising ingredient for preventing AD-type dementia.

Regional neuroinflammation induced by peripheral infection contributes to fatigue-like symptoms: a [18F]DPA-714 positron emission tomography study in rats.

A series of symptoms, including fever, widespread pain, fatigue, and even ageusia, have frequently been reported in the context of various infections, such as COVID-19. Although the pathogenic mechanisms underlying an infection causing fever and pain have been well established, the mechanisms of fatigue induced by infection in specific brain regions remain unclear. To elucidate whether and how the peripheral infection cause fatigue via regional neuroinflammation, we performed a brain-wide investigation of neuroinflammation in a peripheral pseudoinfection rat model using [18F]DPA-714 positron emission tomography (PET) imaging analysis, in which the polyriboinosinic: polyribocytidylic acid (poly I:C) was intraperitoneally injected. Transient fever lasting for several hours and subsequent suppression of spontaneous activity lasting a few days were induced by poly I:C treatment. Significant increase in plasma interleukin (IL)-1β, IL-6 and tumour necrosis factor (TNF)-α were observed at 2 and 4 h following poly I:C treatment. PET imaging analysis revealed that the brain uptake of [18F]DPA-714 was significantly increased in several brain regions one day after poly I:C treatment, such as the dorsal raphe (DR), parvicellular part of red nucleus (RPC), A5 and A7 noradrenergic nucleus, compared with the control group. The accumulation of [18F]DPA-714 in the DR, RPC and A5 was positively correlated with subsequent fatigue-like behavior, and that in the A7 tended to positively correlate with fever. These findings suggest that peripheral infection may trigger regional neuroinflammation, which may cause specific symptoms such as fatigue. A similar mechanism might be involved in COVID-19.

Pretransplant erythroferrone levels are predictive of 1-year all-cause mortality or acute rejection after heart transplantation

Abstract Background/Introduction Heart transplantation (HTx) remains the treatment of choice for selected advanced heart failure (HF) patients. Iron deficiency is a significant factor in the prognosis of HF, and iron metabolism may play a role after HTx since pretransplant hemoglobin levels predict posttransplant 1-year all-cause mortality. In addition, iron deficiency (ID) is known to impact antigen-specific immune response. Purpose The aim of this study was to quantify the impact of pretransplant iron metabolism components on the primary composite outcome 1-year all-cause mortality (ACM) or 1-year acute cellular rejection. Methods This prospective Swiss national cohort study included consecutive patients with HTx between 2008 to 2017. Iron metabolism was assessed measuring plasma iron, ferritin, erythroferrone (ERFE), hepcidin and interleukin-6 immediately before transplant surgery. Endomyocardial biopsies were procured in accordance with the common national posttransplant surveillance protocol. Acute cellular rejection was defined as histological 2R or 3R rejection according to the ISHLT nomenclature 2004 in the diagnosis of heart rejection. Results A total of 276 HTx recipients were included, median age was 52 [IQR 41;59] years, 24.6% (n=68) were females. HTx recipients with incident combined endpoint (n=118, 42.8%) were not significantly different from controls for demographic or transplant operation parameters, donor/recipient gender or HLA mismatch, ferritin, hepcidin (0.5 [IQR 0.5-1.5] vs. 0.5 [IQR 0.5-1.2]; p=0.382) µg/L), interleukin-6, and most biological parameters associated with posttransplant risk. However, participants with incident combined endpoint had lower haemoglobin levels (125 [IQR 102-134] vs. 128 [IQR 114-141 ] g/L; p=0.004), lower Na+ levels (137.5 [IQR 135-139 ] vs. 138 [IQR 136-140] mmol/L; p=0.017), and higher ERFE levels (1.40 [IQR 0.84-1.84 ] vs. 1.19 ng/mL [IQR 0.91-2.92]; p=0.013) compared to those without the endpoint (n=158, 57.2%). The incidence of the combined endpoint was higher in patients presenting with ERFE levels above the third quartile (&amp;gt;2.25 ng/mL; p=0.003). Multivariable analysis using stepwise backward elimination (table) showed that ERFE levels &amp;gt;2.25 ng/mL predicted the incidence of the combined endpoint with an OR of 2.17 (95% CI: 1.19-3.94) (p=0.011). Conclusion The study demonstrates that increased pretransplant ERFE levels are independently associated with 1-year posttransplant all-cause mortality and 1-year acute cellular rejection. This association is in line with results from chronic kidney disease indicating association of ERFE levels with cardiovascular outcome and studies showing iron-induced immune cell activation. In fact, ERFE reduces hepcidin expression as shown in the present and other studies. Thereby, intestinal iron uptake increases resulting in immune cell activation which may explain the higher incidence of heart rejection observed in the present study.FigureTable

Decreased Nrf2 protein level and low sperm quality in intractable spermatocystitis.

To investigate the molecular etiology of low sperm quality in patients with intractable spermatocystitis, spermatozoa samples from patients with persistent hematospermia undergoing transurethral seminal vesiculoscopy and healthy volunteers were utilized. Spermatozoa samples were collected from the seminal vesicles through transurethral seminal vesiculoscopy or by masturbation ejaculation. Sperm quality was analyzed by a WLJY-9000 color semen analysis system. Measurement of tumor necrosis factor alpha (TNFα) and interleukin-6 (IL-6) in the seminal plasma was performed using enzyme-linked immunosorbent assay (ELISA). Measurement of H 2 O 2 in the seminal plasma was performed with a hydrogen peroxide kit. The protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and phosphorylated-Nrf2 (p-Nrf2) were measured by western blot analysis and immunofluorescence assays. Low sperm quality parameters and increased levels of inflammatory cytokines (TNFα, IL-6, and H 2 O 2 ) in the seminal plasma were detected among the semen samples from the patients with persistent hematospermia. Nrf2 and p-Nrf2 were strongly expressed in the nucleus and periphery of human sperm cells, according to the results of the immunofluorescence assays. The protein levels of Nrf2 and p-Nrf2 were significantly lower in the spermatozoa samples from patients with persistent hematospermia than in those from healthy volunteers with normal sperm motility. The results suggested that Nrf2 signaling might play a role in the low sperm quality of patients with intractable spermatocystitis.