IL-6 Concentrations Research Articles

Gut barrier dysfunction, endotoxemia and inflammatory response in STEMI patients and effect of primary PCI

BackgroundGut-derived bacterial and endotoxin translocation induce systemic inflammation, which exerts a pivotal pathogenetic role in all phases of atherosclerosis. ObjectivesTo investigate prospectively the gut barrier function, endotoxin translocation and inflammatory response in ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary artery intervention (PPCI). MethodsTwenty-seven patients with STEMI that underwent successful PPCI were subjected to peripheral blood sampling at 3-time points; before PPCI (day0), 24 h (day1) and 96 h (day4) after PPCI and were compared with 20 chronic coronary syndrome (CCS) patients and 11 healthy controls. Serum ZO-1, I-FABP and endotoxin concentrations were determined by ELISA. Concentrations of cytokines IL-1β, -6, -8, -10 and TNF-α were determined by flow cytometry. ResultsPatients with STEMI before PPCI (day0) had increased serum ZO-1 and endotoxin, both at significantly higher levels compared to CCS patients. STEMI induced also significant increases of the cytokines IL-6, -8 and -10. After PPCI, a significant improvement of gut barrier integrity (ZO-1) and endotoxemia was observed from the first day. At day4 post PPCI, systemic endotoxin and cytokines IL-6, -8 and -10 levels were reduced to control levels. Serum ZO-1 levels were positively correlated with systemic IL-10 concentrations (r = 0.471). ConclusionSTEMI is associated with gut barrier dysfunction, systemic endotoxemia and inflammatory response, which improve rapidly following successful PPCI.

Interleukin-6 in Spinal Cord Injury: Could Immunomodulation Replace Immunosuppression in the Management of Acute Traumatic Spinal Cord Injuries?

Traumatic spinal cord injuries (SCI) result in devastating impairment to an individual's functional ability. The pathophysiology of SCI is related to primary injury but further propagated by secondary reactions to injury, such as inflammation and oxidation. The inflammatory and oxidative cascades ultimately cause demyelination and Wallerian degeneration. Currently, no treatments are available to treat primary or secondary injury in SCI, but some studies have shown promising results by lessening secondary mechanisms of injury. Interleukins (ILs) have been described as key players in the inflammation cascade after neuronal injury; however, their role and possible inhibition in the context of acute traumatic SCIs have not been widely studied. Here, we review the relationship between SCI and IL-6 concentrations in the CSF and serum of individuals after traumatic SCIs. Furthermore, we explore the dual IL-6 signaling pathways and their relevance for future IL-6 targeted therapies in SCI.

Resting Systemic Irisin Concentrations Are Lower in Older versus Younger Males after 12 Weeks of Resistance-Exercise Training While Apelin and IL-15 Concentrations Were Increased in the Whole Cohort

Myokines released by exercise are identified as factors that can influence a person’s health and wellbeing. While myokine secretion in response to an acute bout of endurance and resistance-type exercise has been examined, the influence of resistance-exercise training on myokines at rest is less well established. Therefore, this study was designed to evaluate a panel of myokines at rest following a 12-week resistance-exercise training program in younger and older males. Participants (n = 15) completed a 12-week progressive resistance-exercise training program supervised by a certified fitness professional. The training protocol targeted all major muscle groups of the upper and lower body. Resting blood samples were collected before and after completion of the training program to determine concentrations of apelin, fibroblast growth factor-21 (FGF-21), interleukin (IL)-4, IL-6, IL-7, IL-15, leukemia inhibitory factor (LIF), and irisin. Two-way repeated ANOVAs were used to compare variables between time-points and age groups. There was a main effect of time found for apelin (p = 0.003) and IL-15 (p < 0.001), while no main effects for group or time were found for the other myokines (all p > 0.05). Age group × training status interactions were found for IL-6 (p = 0.04) and irisin (p = 0.014) without pairwise differences for IL-6 (p > 0.05), and younger males had higher concentrations of irisin compared to older males post-training (p = 0.036). Overall, the 12-week resistance-exercise training program significantly increased apelin and IL-15 over time but did not change the other resting myokine concentrations for the younger or older males. However, the higher concentration of irisin in younger versus older males post-training suggests a potential explanation for the anabolic resistance observed with aging.

Vinpocetine, a phosphodiesterase 1 inhibitor, mitigates atopic dermatitis-like skin inflammation.

Atopic dermatitis (AD) is the most common inflammatory pruritic skin disease worldwide, characterized by the infiltration of multiple pathogenic T lymphocytes and histological symptoms such as epidermal and dermal thickening. This study aims to investigate the effect of vinpocetine (Vinp; a phosphodiesterase 1 inhibitor) on a 1-chloro-2,4-dinitrobenzene (DNCB)-induced AD-like model. DNCB (1%) was administered on day 1 in the AD model. Subsequently, from day 14 onward, mice in each group (Vinp-treated groups: 1 mg/kg and 2 mg/kg and dexamethasone- treated group: 2 mg/kg) were administered 100 µl of a specific drug daily, whereas 0.2% DNCB was administered every other day for 30 min over 14 days. The Vinp-treated groups showed improved Eczema Area and Severity Index scores and trans-epidermal water loss, indicating the efficacy of Vinp in improving AD and enhancing skin barrier function. Histological analysis further confirmed the reduction in hyperplasia of the epidermis and the infiltration of inflammatory cells, including macrophages, eosinophils, and mast cells, with Vinp treatment. Moreover, Vinp reduced serum concentrations of IgE, interleukin (IL)-6, IL-13, and monocyte chemotactic protein-1. The mRNA levels of IL-1β, IL-6, Thymic stromal lymphopoietin, and transforming growth factor-beta (TGF-β) were reduced by Vinp treatment. Reduction of TGF-β protein by Vinp in skin tissue was also observed. Collectively, our results underscore the effectiveness of Vinp in mitigating DNCB-induced AD by modulating the expression of various biomarkers. Consequently, Vinp is a promising therapeutic candidate for treating AD.

Correlation of pregnancy duration with hemoglobin, Ret-He, IL-6, activin B, and hepcidin levels in healthy women

Background and objectives. Hepcidin levels always change during pregnancy, resulting in changes in iron hemostasis. Therefore, this study aims to determine the relationship between length of pregnancy and concentrations of hemoglobin, Ret-He, IL-6, activin B and hepcidin in normal pregnant women. Materials and methods. A cross-sectional study was conducted at Jagir Community Health Center. A total of 30 pregnant women were respondents. Hemoglobin and Ret-He levels were measured using a hematology analyzer. IL-6, activin B and hepcidin were measured using ELISA. Results. The results showed that there was a significant difference between the adherent and non-compliant groups in consuming iron supplements on hemoglobin levels (p=0.0042) and IL-6 (p=0.019), while there was no difference in Ret-He levels (p=0.151), activin B (p=0.854) and hepcidin (p=0.189). There was a correlation between gestational age and IL-6 (r=0.207; p=0.273), activin B (r=0.15; p=0.121) and hepcidin (r=0.096; p=0.614). However, there was a negative correlation with hemoglobin (r=0.483; p=0.007) and Ret-He (r=0.505; p=0.004). Conclusion. It was concluded that increasing gestational age will result in a decrease in hemoglobin levels and a decrease in body iron reserves. However, pregnant women who comply with iron supplementation have at least high hemoglobin levels and low IL-6 levels.

Pandanus amaryllifoius Roxb. Leaves Ethanol Extract Ameliorates Lipid and Proinflammatory Cytokines Profiles in a Rat Model of Dyslipidemia.

Dyslipidemia has currently become a major health challenge that still opens for safer and more effective modes of treatment. The plant Pandanus amaryllifolius Roxb. (pandan) has been indicated to contain active ingredients that interfere with the pathological pathway of dyslipidemia. The aim of the study was to test the effects of pandan leaves ethanol extract on lipid and proinflammatory profiles in a rat dyslipidemic model. Dyslipidemia was induced by administration of high-fat feed for 8 weeks. Treatments (vehicle, the reference drug simvastatin at 1.8 mg/kg, and extract at 200, 300 or 600 mg/kg) were given for 4 weeks following the completion of induction. Significant post-treatment decreases in total cholesterol, low density lipoprotein (LDL), and triglyceride levels in groups receiving all doses of extract and simvastatin were observed. Similar results were also found in regards to proinflammatory cytokines levels. Pandan extracts significantly lowered the concentrations of IL-6, TNF-α, and NFκB p65. Characterization of metabolite contents of the extract confirmed the presence of the previously suggested active alkaloids pandamarilactonine-A and B. Taken together, results of the present study implied the ameliorating effects of pandan leaves ethanol extract in dyslipidemic condition which is potential for opening an avenue in combating this essential component of metabolic disorder.

Кореляція маркерів материнського та плодового запалення

Fetal inflammatory response syndrome (IFRS) is an inadequate reaction of the fetal immune system to the inflammatory process in the placenta, which is accompanied by an increase in neonatal mortality and morbidity. Aim - to assess the dependence of IFRS on the markers of the inflammatory process of the mother in premature births in different gestational periods to determine the date of delivery. Materials and methods. 405 mothers with premature singleton deliveries and their premature newborns were examined. The Spearman correlation method was used to calculate the relationship between IL-6 content in the umbilical cord blood of a newborn and laboratory markers of maternal inflammation in peripheral blood (containing leukocytes and rod-shaped neutrophils, C-reactive protein, procalcitonin, pro-inflammatory interleukins), amniotic fluid (glucose, secretory inhibitor of leukocyte proteinase (SILP) and pro-inflammatory interleukins) and cervical mucus (pro-inflammatory interleukins). Results. Between the indicators of the mother's peripheral blood circulation and the value of IL-6, only a moderate connection was found, and the content of IL-6 in the amniotic fluid shows a strong correlation with the concentration of IL-6 in the umbilical cord blood of extremely premature newborns. For SILP, a strong correlation with the laboratory marker SFZV was found. A negative correlation with IL-6 of umbilical cord blood was found in cervical mucus for SILP. Signs of infection in the newborn show a strong dependence on the concentration of C-reactive protein and procalcitonin in the peripheral blood of the mother, but this was not found for extremely premature newborns. A strong correlation was found between the concentration of glucose in the amniotic fluid and signs of infection in premature infants in both gestational categories. Conclusions. Among indicators of peripheral blood circulation of a pregnant woman, none shows a strong correlation with IFRS. The concentration of SILP in the amniotic fluid has a strong correlation with signs of fetal inflammation, regardless of gestational age. The content of SILP in the cervical mucus has a strong negative correlation with the criterion of IFRS in preterm infants against the background of intact fetal membranes. A strong correlation between the glucose content in the amniotic fluid and signs of infection in the premature infant was revealed. For extremely premature newborns, no indicator of the mother's peripheral blood correlates with signs of infection. The research was carried out in accordance with the principles of the Declaration of Helsinki. The research protocol was approved by the Local Ethics Committee of the institution mentioned in the work. Informed consent of the women was obtained for the research. The authors declare no conflict of interest.

Posidonia oceanica (L.) Delile Is a Promising Marine Source Able to Alleviate Imiquimod-Induced Psoriatic Skin Inflammation.

Psoriasis is a chronic immune-mediated inflammatory cutaneous disease characterized by elevated levels of inflammatory cytokines and adipokine Lipocalin-2 (LCN-2). Recently, natural plant-based products have been studied as new antipsoriatic compounds. We investigate the ability of a leaf extract of the marine plant Posidonia oceanica (POE) to inhibit psoriatic dermatitis in C57BL/6 mice treated with Imiquimod (IMQ). One group of mice was topically treated with IMQ (IMQ mice) for 5 days, and a second group received POE orally before each topical IMQ treatment (IMQ-POE mice). Psoriasis Area Severity Index (PASI) score, thickness, and temperature of the skin area treated with IMQ were measured in both groups. Upon sacrifice, the organs were weighed, and skin biopsies and blood samples were collected. Plasma and lesional skin protein expression of IL-17, IL-23, IFN-γ, IL-2, and TNF-α and plasma LCN-2 concentration were evaluated by ELISA. PASI score, thickness, and temperature of lesional skin were reduced in IMQ-POE mice, as were histological features of psoriatic dermatitis and expression of inflammatory cytokines and LCN-2 levels. This preliminary study aims to propose P. oceanica as a promising naturopathic anti-inflammatory treatment that could be introduced in Complementary Medicine for psoriasis.

Hydromorphone combined with ropivacaine for erector spinae plane block in patients undergoing modified radical mastectomy: A prospective randomized controlled trial.

Combining hydromorphone with ropivacaine in ultrasound-guided erector spinae plane blocks enhances postoperative analgesia and reduces interleukin-6 expression in breast surgery patients. In this study, breast cancer patients undergoing modified radical mastectomy were randomized into 3 groups for anesthesia (30 patients in each group): standard general (group C), Erector Spinae Plane Block (ESPB) with ropivacaine (group R), and ESPB with ropivacaine plus hydromorphone (group HR). Diagnosis: Breast cancer patients. Postsurgery, pain levels, IL-6, anesthetic doses, additional analgesia needs, and recovery milestones were compared to evaluate the efficacy of the ESPB enhancements. The 3 groups were not significantly different in baseline characteristics, operation time, number of cases with postoperative nausea, and serum IL-6 concentrations at T1 (the time of being returned to the ward after surgery). At T2 (at 6:00 in the next morning after surgery), the serum IL-6 concentration in group HR was significantly lower than that in groups R and C (P < .05); the intraoperative doses of remifentanil, sufentanil, and propofol were significantly lower in groups HR and R than those in group C (P < .05); Groups HR and R had significantly lower visual analog scale scores at T3 (4 hours postoperatively), T4 (12 hours postoperatively), and T5 (24 hours postoperatively) than those in group C (P < .05); the proportions of patients receiving postoperative remedial analgesia were significantly lower in groups HR and R than in group C (P < .05); groups HR and R had significantly lower proportions of patients with postoperative nausea than group C (P < .05); the time to the first anal exhaust and the time to the first ambulation after surgery were significantly shorter in groups HR and R than those in group C (P < .05). Hydromorphone combined with ropivacaine for ESPB achieved a greater postoperative analgesic effect for patients receiving MRM under general anesthesia. The combined analgesia caused fewer adverse reactions and inhibited the expression level of the inflammatory factor IL-6 more effectively, thereby facilitating postoperative recovery. ESPB using hydromorphone with ropivacaine improved pain control post-MRM, reduced adverse effects, and more effectively suppressed IL-6, enhancing recovery.

Blood serum biomarkers in the dynamics of treatment for cerebrovascular pathology in post-COVID-19 patients

Neurological manifestations after COVID-19 infections can be attributed to chronic immune and inflammatory reactions induced by SARS-CoV-2, as well as endothelial dysfunction and other vascular issues. This study included 24 patients with cerebrovascular disease (CVD) who had contracted COVID-19 1 &amp;ndash; 1.5 years before the examination (experimental group) and 20 patients with CVD who had not previously been infected with the coronavirus (comparison group). Both groups were representative in terms of age and gender. Blood serum biomarkers, including interleukin (IL)-6, endothelin-1 (ET-1), and vascular endothelial growth factor A (VEGF-A), were tested before and after a 14-day standard complex therapy in the hospital at our institute using appropriate enzyme-linked immunosorbent assay reagent kits. Increases in the levels of IL-6 (by 20%), ET-1 (by 200%), and VEGF-A (by 100%) were observed in patients with CVD who had contracted COVID-19 1 &amp;ndash; 1.5 years earlier compared to the comparison group. The effectiveness of a 2-week therapeutic intervention in patients with a history of COVID-19 was found only for VEGF-A: its serum level decreased twofold, leading to the normalization of this indicator. The concentrations of IL-6 and ET-1 were not affected by the treatment. In addition, the serum levels of ET-1 and VEGF-A in unvaccinated individuals exceeded those in vaccinated patients.

Cell-Free Supernatant of Bacillus subtilis G2B9-Q Improves Intestinal Health and Modulates Immune Response to Promote Mouse Recovery in Clostridium perfringens Infection.

Clostridium perfringens is one of the critical causative agents causing diarrhea in piglets, with significant economic losses to the pig industry. Under normal gut microbiota homeostasis and well-managed barns, diarrhea caused by C. perfringens could be controlled. Some reports show that probiotics, such as Bacillus subtilis, are beneficial in preventing necrotic enteritis (NE) in chickens, but few reports on piglets. Clostridium perfringens was found in the piglets' diarrhea with intestinal microbiota dysbiosis in our survey. Bacillus subtilis G2B9-Q, which was isolated from the feces of healthy pigs, was found to have anti-Clostridium activity after screening. Clostridium perfringens was used to challenge mice by intraperitoneal injection for modeling to evaluate the anti-infective activity of cell-free supernatant (CFS) of B. subtilis G2B9-Q and different concentrations of B. subtilis G2B9-Q by oral administration. The results showed that G2B9-Q can mitigate intestinal lesions caused by C. perfringens infection, reduce inflammatory reactions, and modulate intestinal microbiota. The CFS of G2B9-Q can alleviate the pathological damage of intestinal tissues caused by C. perfringens infection, reduce the concentration of TNF-α and IL-10 in the sera of mice, as well as the relative expression levels of alpha toxin (CPA), perfringolysin O (PFO) toxin, IL-10, IL-22, andTNF-α in the jejunum and colon tissues, and alleviate the changes in gut microbiota structure caused by C. perfringens infection, which showed better therapeutic effects and indicated that the metabolites of G2B9-Q are essential mediators for their beneficial effects. Therefore, the CFS of G2B9-Q could potentially replace antibiotics in treating C. perfringens infection.

Changes in Metabolic and Inflammatory Markers after a Combined Exercise Program in Workers: A Randomized Controlled Trial.

We investigated the effects of a 16-week combined exercise training on body composition, metabolic and inflammatory markers in sedentary middle-aged workers. We also assessed whether significant alterations in metabolic markers were associated with changes in health-related outcomes. This randomized controlled trial involved 46 participants randomly allocated into control and exercise groups. The exercise group performed 16-week combined aerobic and resistance training for 75 min/session, 3 times/week. Fasting blood samples were collected at baseline and after 16-week intervention to determine lipid profile, metabolic and inflammatory markers as primary outcomes. A total of 36 participants completed the intervention (53.70 ± 6.92 years old) (n = 18 in each group). Waist circumference (interaction effect: F = 7.423, p = 0.002), fat mass (interaction effect: F = 5.070, p = 0.011), and muscle mass (interaction effect: F = 5.420, p = 0.007) were improved in the exercise group compared to the control group. Fasting glucose increased after the 16-week follow-up (time effect: F = 73.253, p < 0.001), without an intergroup difference. Insulin levels were greater in the control compared to exercise group (group effect: F = 6.509, p = 0.015). The control group tended to increase the HOMA-IR index (interaction effect: F = 3.493, p = 0.070) and to decrease the QUICKI index (interaction effect: F = 3.364, p = 0.075) to a greater extent compared to the exercise group. Exercise group reduced leptin (interaction effect: F = 11.175, p = 0.002) and adiponectin (interaction effect: F = 4.437, p = 0.043) concentrations in a greater magnitude than control group. IL-6 (time effect: F = 17.767, p < 0.001) and TNF-α (time effect: F = 9.781, p = 0.004) concentrations decreased after the intervention, without an intergroup difference. IL-17A levels increased in the control compared to exercise group (interaction effect: F = 5.010, p = 0.033). Effects on adiponectin, IL-6 and IL-17A levels seem to depend on baseline BMI, age, and sex. Percentage changes in leptin correlated positively with changes in HOMA-IR index in the exercise (r = 0.565, p = 0.015) and control (r = 0.670, p = 0.002) groups. A combined training program can be an effective strategy to improve body composition and inflammatory markers and prevent marked reductions in insulin sensitivity among middle-aged workers.

Dysfunction of the Murine Liver with Aging and Its Improvement with the Continuous Consumption of Enterococcus faecalis EC-12.

Chronic inflammation is involved in the development of age-related diseases. Given its persistence, controlling chronic inflammation is essential for preventing age-related diseases. In this study, we investigated the effects of Enterococcus faecalis EC-12 (EC-12), which has immunomodulatory and antioxidant effects, on liver gene expression and aging phenomena in mice. Short-term EC-12 administration stimulated the expression of genes involved in lipid synthesis and metabolism in the liver. Furthermore, long-term EC-12 administration from 10 weeks to 1.5 years of age resulted in significant increases in blood interleukin (IL)-6 and IL-10 concentrations (both p < 0.05) and a significant decrease in the monocyte chemotactic protein-1 concentration (p < 0.05). These results indicated pathologic improvement, such as suppression of fat degeneration in the liver. These results suggest that continuous EC-12 intake from a young age can suppress liver function abnormalities, which is one of the aging phenomena in old age, and contribute to health in old age.

Prodromic Inflammatory-Oxidative Stress in Peritoneal Leukocytes of Triple-Transgenic Mice for Alzheimer's Disease.

Inflammatory-oxidative stress is known to be pivotal in the pathobiology of Alzheimer's disease (AD), but the involvement of this stress at the peripheral level in the disease's onset has been scarcely studied. This study investigated the pro-inflammatory profile and oxidative stress parameters in peritoneal leukocytes from female triple-transgenic mice for AD (3xTgAD) and non-transgenic mice (NTg). Peritoneal leukocytes were obtained at 2, 4, 6, 12, and 15 months of age. The concentrations of TNFα, INFγ, IL-1β, IL-2, IL-6, IL-17, and IL-10 released in cultures without stimuli and mitogen concanavalin A and lipopolysaccharide presence were measured. The concentrations of reduced glutathione (GSH), oxidized glutathione (GSSG), lipid peroxidation, and Hsp70 were also analyzed in the peritoneal cells. Our results showed that although there was a lower release of pro-inflammatory cytokines by 3xTgAD mice, this response was uncontrolled and overstimulated, especially at a prodromal stage at 2 months of age. In addition, there were lower concentrations of GSH in leukocytes from 3xTgAD and higher amounts of lipid peroxides at 2 and 4 months, as well as, at 6 months, a lower concentration of Hsp70. In conclusion, 3xTgAD mice show a worse pro-inflammatory response and higher oxidative stress than NTg mice during the prodromal stages, potentially supporting the idea that Alzheimer's disease could be a consequence of peripheral alteration in the leukocyte inflammation-oxidation state.

Integrated microbiome and metabolome analysis reveals that new insight into Radix pseudostellariae polysaccharide enhances PRRSV inactivated vaccine.

In this study, we investigated how Radix pseudostellariae polysaccharide (RPP) enhances the immune response of the inactivated porcine reproductive and respiratory syndrome virus (PRRSV) vaccine through interactions with the microbiome and metabolome. We pretreated sows with 10 mg/kg body weight of RPP via drinking water for 7 days prior to intramuscular injection of the PRRSV vaccine. This significantly increased the concentrations of PRRSV GP5 protein antibody, interleukin (IL)-2, IL-4, IL-10, and interferon (IFN)-γ. Oral administration of RPP also significantly improved the abundance of beneficial bacteria in the stool, such as Parabacteroides distasonis, Prevotella_copri, Eubacterium_sp., and Clostridium_sp._CAG:226, and decreased the levels of potentially pathogenic bacteria, such as Paraeggerthella and [Clostridium] innocuum, compared to the vaccine alone. These bacterial changes were confirmed using quantitative real-time polymerase chain reaction (Q-PCR). Moreover, RPP treatment significantly increased the blood concentrations of L-theanine, taurodeoxycholic acid (TDCA), and N-arachidonoyl proline, and decreased the levels of L-glutamine, oclacitinib, lipoxin C4, and leukotriene C5 in sows after immunization (p< 0.05). The concentrations of various blood metabolites were validated using sandwich enzyme-linked immunosorbent assay (ELISA), confirming the accuracy of the metabolomics data. Intriguingly, the integration of microbiome and metabolome analyses highlighted the significance of Prevotella_copri and TDCA. We consequently developed a mouse immunity model using GP5 protein and discovered that oral administration of RPP significantly enhanced the levels of GP5 protein antibodies, IL-2, IL-4, IL-10, and IFN-γ in mouse serum. It also increased the number of CD3+ and CD3+CD4+ cells in the spleen. Additionally, Prevotella_copri was administered into the large intestine via the anus for 7 days prior to the intramuscular injection of the PRRSV GP5 protein. The results demonstrated a significant increase in TDCA and GP5 antibody concentration in the mouse serum, indicating that RPP modulates Prevotella_copri to elevate its metabolite TDCA, thereby enhancing the GP5 antibody level. In conclusion, oral administration of 10 mg/kg RPP optimizes gut flora diversity and blood metabolites, particularly Prevotella_copri and TDCA, thereby improving the immune response to the inactivated PRRSV vaccine.

Astaxanthin treatment decreases pro-inflammatory cytokines and improves reproductive outcomes in patients with polycystic ovary syndrome undergoing assisted reproductive technology: A randomized clinical trial.

In a randomized, triple-blind, placebo-controlled clinical trial (RCT), we investigated the effect of astaxanthin (AST) on pro-inflammatory cytokines, oxidative stress (OS) markers, and assisted reproductive technology (ART) outcomes in 44 infertile Polycystic Ovary Syndrome (PCOS) patients. Patients with PCOS were randomly divided into two groups. The intervention group received 6 mg AST, and the control group received placebo daily for 8 weeks. Blood samples were obtained from all patients before and after intervention and follicular fluid (FF) was collected during the ART procedure. Interleukin (IL) -6, IL-1β were evaluated from serum samples and FF and OS markers (malondialdehyde [MDA], catalase [CAT], superoxide dismutase [SOD], and reactive oxygen species [ROS]) were measured from FF. The groups were compared for ART outcomes as well. A significant decrease in IL-6 and IL-1β concentrations (both, P=<0.01) serum levels was found following AST treatment. FF cytokine levels and OS markers did not differ significantly between the groups. Reproductive outcomes, including the number of oocytes retrieved (P= 0.01), the MII oocyte count (P= 0.007), oocyte maturity rate (MII %) (P= 0.02) and number of frozen embryos (P= 0.03) significantly improved after intervention. No significant differences were found in chemical, clinical and multiple pregnancies between the groups. AST pretreatment may modify inflammation and improve ART outcomes in PCOS infertile patients. Further investigations are recommended to verify these findings.

Cutibacterium acnes contamination does not enhance the proinflammatory profile of platelet concentrates.

Cutibacterium acnes, a common anaerobic platelet concentrate (PC) contaminant, has been associated with rare mild adverse transfusion reactions and is often considered a harmless commensal. Notably, C. acnes can cause chronic infections and has been shown to induce the release of proinflammatory cytokines by immune cells. Since elevated concentrations of proinflammatory factors in PCs have been linked to noninfectious adverse reactions, this study aimed to assess whether C. acnes could elicit the release and accumulation of proinflammatory factors during PC storage, thereby enhancing the risk of such reactions. Four ABO-matched buffy coat PCs were pooled and split into six units, each were inoculated with either saline (negative control), a Staphylococcus aureus isolate (positive control, 30 colony forming units [CFU]/unit), or four C. acnes PC isolates (10 CFU/mL) and stored at 20-24°C with agitation. Bacterial counts, platelet activation, and concentration of proinflammatory factors were assessed on days 0, 3, and 5. N = 3. C. acnes counts remained stable, while S. aureus proliferated reaching 108CFU/mL by the end of PC storage. By day 5, no significant differences in platelet activation or proinflammatory cytokine profiles were observed in C. acnes-contaminated PCs compared to the negative control (p > .05), while there was a significant increase (p ≤ .05) in sCD40L concentration (day 3), and platelet activation and IL-8 concentration (day 5) in S. aureus-contaminated units. C. acnes contamination does not promote the accumulation of proinflammatory factors in the absence of proliferation during storage and may not enhance the risk of inflammatory reactions when transfused to patients.

IL-9 Is a Biomarker of BIA-ALCL Detected Rapidly by Lateral Flow Assay.

A delayed seroma around breast implants is the most common clinical presentation of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL). Interleukin-9 (IL-9), IL-10, and IL-13 concentrations are significantly higher in BIA-ALCL than in benign seromas, offering a means to distinguish between these conditions. The aim of this research was to test the ability of a lateral flow assay (LFA) to detect high concentrations of IL-9 rapidly. In addition, the authors compared CD30 and IL-9 LFAs for distinguishing BIA-ALCL from benign seromas. Samples of 26 seromas (15 benign, 11 malignant) were tested on in-house-prepared LFA strips for IL-9 and CD30. Nanoparticle-conjugated antibodies specific to IL-9 and CD30 were used for detection. The intensity of both the test line (TL) and a control line (CL) were analyzed and the TL/CL ratio was calculated. IL-9 protein and IL-9 transcription factor PU.1 were stained in BIA-ALCL lines and clinical samples. The IL-9 LFA could reliably distinguish BIA-ALCL from benign seromas when the IL-9 concentration was >10 ng/ml. The CD30 LFA was positive in all 11 malignant cases. In 1 case with only faint CD30 and IL-10 TLs, the IL-9 LFA was clearly positive. Immunohistochemistry showed that IL-9 and PU.1 were present in tumor cells in BIA-ALCL lines and clinical samples. Concentrations of IL-9 >10 ng/ml reliably distinguished BIA-ALCL from benign seromas. Moreover, the IL-9 LFA could detect BIA-ALCL when both the CD30 and IL-10 LFAs were not definitive, suggesting a multiplex LFA measuring IL-9, CD30, and IL-10 might be more effective in detecting BIA-ALCL in selected cases.

Exudative Age-Related Macular Degeneration: Association between Treatment Efficacy and Single-Nucleotide Variants in RAD51B, TRIB1, COL8A1, COL10A1, IL-9, IL-10, and VEGFA Genes.

Age-related macular degeneration (AMD) is a progressive neurodegenerative condition leading to vision loss and eventual blindness, with exudative AMD posing a heightened risk due to choroidal neovascularization and localized edema. Therapies targeting the VEGF pathway aim to address this mechanism for treatment effectiveness. Our study aimed to evaluate associations between specific genetic variants (RAD51B rs8017304, rs2588809; TRIB1 rs6987702, rs4351379; COL8A1 rs13095226; COL10A1 rs1064583; IL-9 rs1859430, rs2069870, rs11741137, rs2069885, rs2069884; IL-10 rs1800871, rs1800872, rs1800896; VEGFA rs1570360, rs699947, rs3025033, rs2146323) and the response to anti-VEGF treatment for exudative AMD. We enrolled 119 patients with exudative AMD categorized as responders or non-responders based on their response to anti-VEGF treatment. Statistical analysis revealed that RAD51B rs8017304 heterozygous and homozygous minor allele carriers had increased CMT before treatment compared to wild-type genotype carriers (p = 0.004). Additionally, TRIB1 rs4351379 heterozygous and homozygous minor allele carriers exhibited a greater decrease in central macular thickness (CMT) after 6 months of treatment than wild-type genotype carriers (p = 0.030). IL-9 rs1859430, rs2069870, and rs2069884 heterozygous and homozygous minor allele carriers had worse BCVA before treatment than wild-type genotype carriers (p = 0.018, p = 0.012, p = 0.041, respectively). Conversely, IL-9 rs2069885 heterozygous and homozygous minor allele carriers showed greater improvement in BCVA after 6 months compared to wild-type genotype carriers (p = 0.032). Furthermore, VEGFA rs699947 heterozygous and homozygous minor allele carriers had better BCVA before treatment and after 3 and 6 months of treatment than wild-type genotype carriers (p = 0.003, p = 0.022, respectively), with these carriers also exhibiting higher CMT after 6 months of anti-VEGF treatment (p = 0.032). Not all results remained statistically significant under this stringent correction for multiple comparisons. The comparisons of the serum concentrations of IL-10, VEGF-A, and VEGF-R2/KDR between non-responders and responders did not yield statistically significant differences. Our study identified significant associations between genetic variants, including RAD51B rs8017304, TRIB1 rs4351379, IL-9 rs1859430, rs2069870, rs2069884, rs2069885, and VEGFA rs699947, and parameters related to the efficacy of exudative AMD treatment, such as BCVA and CMT.

Distinct dynamics of mRNA LNPs in mice and nonhuman primates revealed by in vivo imaging

The characterization of vaccine distribution to relevant tissues after in vivo administration is critical to understanding their mechanisms of action. Vaccines based on mRNA lipid nanoparticles (LNPs) are now being widely considered against infectious diseases and cancer. Here, we used in vivo imaging approaches to compare the trafficking of two LNP formulations encapsulating mRNA following intramuscular administration: DLin-MC3-DMA (MC3) and the recently developed DOG-IM4. The mRNA formulated in DOG-IM4 LNPs persisted at the injection site, whereas mRNA formulated in MC3 LNPs rapidly migrated to the draining lymph nodes. Furthermore, MC3 LNPs induced the fastest increase in blood neutrophil counts after injection and greater inflammation, as shown by IL-1RA, IL-15, CCL-1, and IL-6 concentrations in nonhuman primate sera. These observations highlight the influence of the nature of the LNP on mRNA vaccine distribution and early immune responses.