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To study serum interleukin-6(IL-6), interleukin-8(IL-8) and interleukin-10(IL-10) levels in Epilpetic encephalopathy with spike-wave activation in sleep(EE-SWAS), drug refractory epilepsy(DRE) and well controlled epilepsy(WCE). Children(2–12 years) with immunotherapy naïve EE-SWAS, DRE and WCE were enrolled. Valid psychometric tools were used to assess cognition and behavior. Children with EE-SWAS were longitudinally followed. They received a three-month steroid course alongwith the ongoing antiseizure drugs. Electroclinical responders were defined as change in social quotient by 5-points with improvement in atleast one behavioral domain by 5-points and 50 % reduction in mean seizure frequency if active seizures were present alongwith a 25 % reduction in Spike-wave-index(SWI) at three months. Change in serum Interleukin levels at one month follow up was compared between participants who eventually became responders or non-responders at three months. Twenty children with EE-SWAS, 18 with DRE and WCE each were enrolled. Serum IL-6(pg/ml){(EE-SWAS: 3.775(IQR 2.205, 11.28); DRE: 3.01(IQR 2.04, 4.56); WCE: 1.655(IQR 1.27, 2.29), p = 0.0065} and IL-8(pg/ml){(EE-SWAS: 103.2(IQR 34.01, 200.82); DRE: 19.595(IQR 16.54, 39.7); WCE: 18.97(IQR 16.54, 21.91) p = 0.0002} was significantly different between the three groups. In EE-SWAS group 12/20(60 %) showed electroclinical response to steroids. Responders had significant reduction in IL6 levels (pg/ml){4.045(IQR 2.605, 18.96) to 1.13(IQR 054, 1.74)} at one month follow up compared to non responders {3.12(IQR 1.655, 5.27) to 4.37(IQR 2.83, 9.855)} (p = 0.0069). Proinflammatory cytokines (IL-6 and IL-8) are significantly elevated in EE-SWAS compared to DRE and WCE. Reduction in IL-6 levels at one month post-therapy predicted electroclinical responders at 3months follow up. • The neuroinflammatory nexus of EE-SWAS is distinct from DRE and WCE with elevated serum IL-6 and Il-8. • Serum IL-6 is elevated in both DRE and EE-SWAS suggesting a role in epileptogenesis in both these conditions. • A decline in serum IL-6 levels at 4-weeks post steroid therapy in EE-SWAS may predict response to steroids at 3 months. [ABSTRACT FROM AUTHOR]

Copyright of Nefrologia is the property of Revista Nefrologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: This study investigated the clinical characteristics and outcomes of kidney transplant recipients (KTRs) who contracted COVID-19. Methods: In this retrospective study, we analyzed data from 122 KTRs confirmed to have COVID-19. Results: The mean age in patients with mild COVID-19 disease was 37.1 ± 9.1 years, whereas those with moderate and severe disease were 44.7 ± 13.7 and 48.1 ± 11.2 years, respectively (P = 0.02). The median neutrophil-to-lymphocyte ratio was 4.2 (interquartile range [IQR] 3.0–6.8) for mild cases, 6.5 (IQR: 5.0–10.8) for moderate cases, and 19 (IQR: 7.0–24.7) for severe cases (P = 0.008). The median C-reactive protein (CRP) levels (mg/L) were 19.5 (1QR: 5.0–156.3), 53.9 (1QR: 31.5–96.0), and 63.4 (1QR: 23.2–228) for mild, moderate, and severe cases, respectively (P = 0.006). Acute kidney injury occurred in 13.6%, 60%, and 81.57% of patients with mild, moderate, and severe cases, respectively (P = 0.004). Risk factors for a composite outcome of death and dialysis included age >50 years (odds ratio [OR]: 3.25, confidence interval [CI]: 1.25–7.7; P = 0.027), nonvaccinated status (OR 2.87, CI: 1.56–4.18; P = 0.008), graft dysfunction (OR: 2.1, CI: 1.2–5.9; P = 0.034), and CT severity index (CTSI) >13 (OR 3.3, CI: 1.5–5.9; P = 0.040). Conclusions: COVID-19 infection in KTRs is linked to a high mortality rate. Advanced age, lymphopenia, elevated CRP levels, and acute graft dysfunction are associated with disease severity. Age >50 years, nonvaccinated status, graft dysfunction, and a CTSI >13 are risk factors for the composite outcome of death and dialysis. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Journal of Dental Hygiene is the property of Canadian Dental Hygienists Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Severely ill patients with coronavirus disease 2019 (COVID‐19) show an increased risk of new‐onset atrioventricular blocks (AVBs), associated with high rates of short‐term mortality. Recent data suggest that the uncontrolled inflammatory activation observed in these patients, specifically interleukin (IL)‐6 elevation, may play an important pathogenic role by directly affecting cardiac electrophysiology. The aim of our study was to assess the acute impact of IL‐6 changes on electrocardiographic indices of atrioventricular conduction in severe COVID‐19. Methods: We investigated (1) the behavior of PR‐interval and PR‐segment in patients with severe COVID‐19 during active phase and recovery, and (2) their association with circulating IL‐6 levels over time. Results: During active disease, COVID‐19 patients showed a significant increase of PR‐interval and PR‐segment. Such atrioventricular delay was transient as these parameters rapidly normalized during recovery. PR‐indices significantly correlated with circulating IL‐6 levels over time. All these changes and correlations persisted also in the absence of laboratory signs of cardiac strain/injury or concomitant treatment with PR‐prolonging drugs, repurposed or not. Conclusions: Our study provides evidence that in patients with severe COVID‐19 and high‐grade systemic inflammation, IL‐6 elevation is associated with a significant delay of atrioventricular conduction, independent of concomitant confounding factors. While transient, such alterations may enhance the risk of severe AVB and associated short‐term mortality. Our data provide further support to current anti‐inflammatory strategies for severe COVID‐19, including IL‐6 antagonists. [ABSTRACT FROM AUTHOR]

Objectives Increasing evidence demonstrated that there are altered levels of both pro-and anti-inflammatory cytokines in autism spectrum disorder (ASD) and pointed out that immune dysfunction may also relate to social deficits. This study aimed to investigate the effect of aquatic exercise combined with vitamin D supplementation on social interaction and two related cytokines (Interleukin-6 and Interleukin-10) in children with ASD. Materials & Methods Forty boys with ASD (mean age: 10.90; age range: 6-14 years) were randomly assigned to the three interventions (groups 1, 2, and 3) and one control group (each 10 participants). Participants in the group 1 and 3 received a 10-week aquatic exercise program. Subjects in groups 2 and 3 took orally 50,000 IU of vitamin D3/week. This study evaluated the serum levels of IL-6 and IL-10, as well as the participants' social interaction at baseline and postintervention. Results Compared to the control group, all three interventions improved social skills scores (p< 0.001). Surprisingly, the combination strategy could significantly reduce IL-6 and increase IL-10 serum levels in children with ASD. Conclusion Aqua-based exercise programs combined with vitamin D supplementation are recommended to benefit children with ASD and improve social and communication dysfunction. [ABSTRACT FROM AUTHOR]

Efficacy of dexmedetomidine (DEX) as a cardioprotective agent in Indonesian children undergoing classic tetralogy of Fallot (TOF) repair with cardiopulmonary bypass (CPB). A prospective, parallel trial using block randomization along with double-blinded preparation of treatment agents by other parties. National Cardiovascular Center Harapan Kita, Indonesia. Sixty-six children with classic TOF scheduled for corrective surgery. No children were excluded. All patients had fulfilled the criteria for analysis. A total of 0.5 µg/kg bolus of DEX was added to the CPB priming solution, followed by 0.25 µg/kg/h maintenance during bypass. The placebo group used normal saline. Follow-ups were up to 30 days. Troponin I was lower in the DEX group at 6 hours (30.48 ± 19.33 v 42.73 ± 27.16, p = 0.039) and 24 hours after CPB (8.89 ± 5.42 v 14.04 ± 11.17, p = 0.02). Within a similar timeframe, DEX successfully lowered interleukin-6 (p = 0.03; p = 0.035, respectively). Lactate was lower in the Dex group at 1, 6, and 24 hours after CPB (p < 0.01; p = 0.048; p = 0.035; respectively). Dexmedetomidine increased cardiac output and index from 6 hours after bypass, but vice versa in systemic vascular resistance. Reduction of vasoactive inotropic score was seen during intensive care unit monitoring in the Dex group (p = 0.049). Nevertheless, DEX did not significantly affect the length of ventilation (p = 0.313), intensive care unit stay (p = 0.087), and mortality (p > 0.99). Dexmedetomidine during CPB is an effective cardioprotective agent in TOF children having surgery. Postoperative mortality was comparable across groups. [ABSTRACT FROM AUTHOR]

Maxillofacial trauma often brings significant challenges for surgeons in terms of preoperative oedema. Steroids offer oedema reduction, yet potentially increase the risks of postoperative infection. This study explores procalcitonin (PCT), as a marker for bacterial infection risk, and interleukins IL-6 and IL-10, which respectively signify pro-inflammatory and anti-inflammatory responses, as potential indicators of infection and inflammation in these trauma cases and thereby aid in refining perioperative guidelines for the use of steroids. A prospective study was conducted at a tertiary public hospital in India from 2019 to 2022 on patients >18 years with facial trauma. After specific exclusions, patients were randomised into steroid (Group A) and non-steroid (Group B) groups. Various parameters including oedema, PCT, IL-6, and IL-10 levels were measured and analysed using SPSS software. Out of 80 patients, 44 were in Group A and 36 in Group B. Post-24 hours, Group A showed significant oedema reduction, with 25 patients displaying a decline to mild oedema, versus 10 patients in Group B (p = 0.034). However, Group A witnessed a higher infection risk, with 20 patients showing positive wound cultures versus three in Group B. Subgroup analysis revealed a link between higher PCT levels and infections (p = 0.039). Additionally, Group A showed less intraoperative bleeding and reduced operating time. While perioperative steroids mitigate swelling, they might increase postoperative infection risk. Elevated PCT levels indicate potential wound infections, suggesting those patients should avoid perioperative steroids. IL-6 and IL-10 trends during perioperative phases can predict pronounced oedema outcomes. [ABSTRACT FROM AUTHOR]

Neutralization of Interleukin (IL)-6-signaling by antibodies is considered a promising tool for the treatment of osteoarthritis (OA). To gain further insight into this potential treatment, this study investigated the effects of IL-6-signaling and IL-6 neutralization on chondrocyte metabolism and the release of IL-6-signaling-related mediators by human chondrocytes. Chondrocytes were collected from 49 patients with advanced knee/hip OA or femoral neck fracture. Isolated chondrocytes were stimulated with different mediators to analyze the release of IL-6, soluble IL-6 receptor (sIL-6R) and soluble gp130 (sgp130). The effect of IL-6 and IL-6/sIL-6R complex as well as neutralization of IL-6-signaling on the metabolism was analyzed. OA chondrocytes showed high basal IL-6 production and release, which was strongly negatively correlated with the production of cartilage-matrix-proteins. Chondrocytes produced and released sIL-6R and sgp130. The IL-6/sIL-6R complex significantly increased nitric oxide, prostaglandin E 2 and matrix metalloproteinase 1 production, decreased Pro-Collagen Type II and mitochondrial ATP production, and increased glycolysis in OA chondrocytes. Neutralization of IL-6-signaling by antibodies did not significantly affect the metabolism of OA chondrocytes, but blocking of glycoprotein 130 (gp130)-signaling by SC144 significantly reduced the basal IL-6 release. Although IL-6 trans-signaling induced by IL-6/sIL-6R complex negatively affects OA chondrocytes, antibodies against IL-6 or IL-6R did not affect chondrocyte metabolism. Since inhibition of gp130-signaling reduced the enhanced basal release of IL-6, interfering with gp130-signaling may ameliorate OA progression because high cellular release of IL-6 correlates with reduced production of cartilage-matrix-proteins. [ABSTRACT FROM AUTHOR]

The aim of this study was to systematically review and analyze differences in the levels of C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) comparing metabolically healthy but obese (MHO) with metabolically healthy non-obese (MHNO), metabolically unhealthy non-obese (MUNO), and metabolically unhealthy obese (MUO) subjects. We searched PubMed, Embase, Web of Science, and Scopus for studies that matched the relevant search terms. Differences in inflammatory marker levels between MHO and the other three phenotypes were pooled as standardized mean differences (SMD) or differences of medians (DM) using a random-effects model. We included 91 studies reporting data on 435,007 individuals. The CRP levels were higher in MHO than in MHNO subjects (SMD = 0.63, 95% CI: 0.49, 0.76; DM = 0.83 mg/L, 95% CI: 0.56, 1.11). The CRP levels were higher in MHO than in MUNO subjects (SMD = 0.16, 95% CI: 0.05, 0.28; DM = 0.39 mg/L, 95% CI: 0.09, 0.69). The CRP levels were lower in MHO than in MUO individuals (SMD = −0.43, 95% CI: −0.54, −0.31; DM = −0.82 mg/L, 95% CI: −1.16, −0.48). The IL-6 levels in MHO were higher than in MHNO while lower than in MUO subjects. The TNF-α levels in MHO were higher than in MHNO individuals. This review provides evidence that CRP levels in MHO are higher than in MHNO and MUNO subjects but lower than in MUO individuals. Additionally, IL-6 levels in MHO are higher than in MHNO but lower than in MUO subjects, and TNF-α levels in MHO are higher than in MHNO individuals. PROSPERO number: CRD42021234948. • Levels of inflammatory markers in metabolically healthy obese (MHO): the first meta-analysis. • CRP levels in MHO are higher than in MHNO and MUNO but lower than in MUO subjects. • IL-6 levels in MHO are higher than in MHNO but lower than in MUO subjects. • TNF-α levels in MHO are higher than in MHNO subjects. [ABSTRACT FROM AUTHOR]

Inflammatory cytokines like tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 can cause brain injury, slow recovery, and adverse effects (ADEs) in ischemic stroke (IS) patients treated with recombinant tissue plasminogen activator (rtPA). We explored the relationship between selected polymorphisms within TNF-α, IL-1β and IL-6 genes, and post-IS outcome and ADEs in patients treated with rtPA. One hundred and sixty-six patients with IS treated with rtPA were included in this study. The modified Rankin Scale (mRS) was used to assess functional recovery 3 months after IS likewise thrombolytic therapy efficacy. Patients were classified into groups with favorable (0–1) or poor recovery based on their mRS score at the ninetieth day post-IS. During hospitalization, ADEs following rtPA were monitored. TNF-α-308 G/A (rs1800629), IL-1β-511 G/A (rs16944), and IL-6-174 G/C (rs1800795) polymorphisms were genotyped using Real-Time PCR. SPSS software version 22.0 was used for statistical analyses. Patients with the TNF-α-308 G/A GG genotype had a higher mean NIHSS value at admission (12.75 ± 5.176) than those carrying A-allele (10.56 ± 3.979;p = 0.016). Individuals with the CC genotype of the IL-6-174 G/C polymorphism had significantly lower NIHSS scores (8.79 ± 5.053) than those with G-allele (12.06 ± 6.562) 24 hours after rtPA (p = 0.050). Patients with the GG genotype of the IL-6-174 G/C polymorphism had a significantly poorer outcome (p = 0.024; OR = 2.339; 95%CI 1.121–4.880), while patients who were G-allele carriers of the Il-6–174 G/C polymorphism and had the AA genotype of the IL-1β-511 G/A polymorphism were statistically significantly more likely to experience hemorrhagic transformation (p = 0.046; OR = 2.7273; 95%CI 1.0414–7.1426). GG genotype of the IL-6-174 G/C polymorphism is associated with poor recovery after IS treated with rtPA therapy. [ABSTRACT FROM AUTHOR]

The diagnosis of persistent infection prior to second-stage reimplantation in 2-stage exchanges for periprosthetic joint infection (PJI) can be challenging as there is no optimal diagnostic tool. This study investigates the usefulness of pre-reimplantation serum C-reactive protein (CRP) and interleukin-6 (IL-6) and its change between both stages to identify patients who have subsequent PJI. There were 125 patients who underwent planned 2-stage exchange for chronic knee or hip PJI from a single center retrospectively identified. Patients were included if preoperative CRP and IL-6 were available for both stages. Subsequent PJI was defined as 2 positive microbiological cultures at reimplantation or subsequent surgery or death due to PJI during follow-up. Prior to reimplantation, the median serum CRP (total knee arthroplasties [TKAs]: 1.0 versus 0.5 mg/dL, P =.028; total hip arthroplasties [THAs]: 1.3 versus 0.5 mg/dL, P =.015) and median IL-6 (TKA: 8.0 versus 6.0 pg/mL, P =.052; THA: 7.0 versus 6.0 pg/mL, P =.239) were higher in patients who had subsequent PJI. The IL-6 and CRP values showed moderate sensitivity (TKA/CRP: 66.7%; THA/CRP: 58.8%; TKA/IL-6: 46.7%; THA/IL-6: 35.3%) and good specificity (TKA/CRP: 66.7%; THA/CRP: 81.0%; TKA/IL-6: 86.3%; THA/IL-6: 83.3%). The change in CRP and IL-6 between the stages did not differ between the groups, respectively. Serum CRP and IL-6 show low to moderate sensitivity and good specificity in the diagnosis of subsequent PJI prior to reimplantation, which questions their usefulness as a rule-out test. Furthermore, the change in between stages does not appear to identify subsequent PJI. [ABSTRACT FROM AUTHOR]

Despite optimal treatment, a residual inflammatory risk often remains in patients with atherosclerotic cardiovascular disease. In a US-based phase 2 trial, ziltivekimab, a fully human monoclonal antibody targeting the interleukin-6 ligand, significantly reduced biomarkers of inflammation compared with placebo in patients at high atherosclerotic risk. Here, we report the efficacy and safety of ziltivekimab in Japanese patients. RESCUE-2 was a randomized, double-blind, 12-week, phase 2 trial. Participants aged ≥20 years with stage 3–5 non-dialysis-dependent chronic kidney disease and high-sensitivity C-reactive protein (hsCRP) ≥2 mg/L were randomized to receive placebo (n = 13) or subcutaneous ziltivekimab 15 mg (n = 11) or 30 mg (n = 12) at Weeks 0, 4, and 8. The primary endpoint was percentage change in hsCRP levels from baseline to end of treatment (EOT; mean of Week 10 and Week 12 values). At EOT, median hsCRP levels were reduced by 96.2 % in the 15 mg group (p < 0.0001 versus placebo), by 93.4 % in the 30 mg group (p = 0.002 versus placebo), and by 27.0 % in the placebo group. Serum amyloid A and fibrinogen levels were also reduced significantly. Ziltivekimab was well tolerated and did not affect total cholesterol to high-density lipoprotein cholesterol ratios. There was a small, but statistically significant increase in triglyceride levels with ziltivekimab 15 mg and 30 mg compared with placebo. The efficacy and safety results support the development of ziltivekimab for secondary prevention and the treatment of patients at high atherosclerotic risk. ClinicalTrials.gov identifier, NCT04626505. [Display omitted] • Systemic inflammation is highly prevalent in chronic kidney disease (CKD). • It is defined as high-sensitivity C-reactive protein (hsCRP) ≥2 mg/L. • Ziltivekimab is a fully human monoclonal antibody against the interleukin-6 ligand. • The RESCUE-2 trial included 36 Japanese adults with CKD stage 3–5 and hsCRP ≥2 mg/L. • In RESCUE-2, ziltivekimab reduced hsCRP vs placebo (p < 0.001) and was well tolerated. [ABSTRACT FROM AUTHOR]

In hepatocellular carcinoma (HCC), sorafenib (Sora) efficacy is limited by primary and/or acquired resistance. Emerging evidence shows that the inflammatory factor interleukin 6 (IL-6) plays a role in Sora resistance. Norcantharidin (NCTD), a derivative of cantharidine, was identified as a potent IL-6 inhibitor. Thus, in this study, we evaluated NCTD ability to improve the Sora efficacy in HCC and its underlying molecular mechanisms. Male Sprague Dawely rats were administered NCTD (0.1 mg/kg/day; orally) or Sora (10 mg/kg day; orally) or combination for 6 weeks after HCC induction using thioacetamide (200 mg/kg; ip; 2 times/wk) for 16 weeks. Our results showed that NCTD greatly enhanced Sora activity against HCC and potentiated Sora-induced oxidative stress. NCTD enhanced Sora-induced tumor immunity reactivation by decreasing both fibrinogen-like protein 1 level and increasing both tumor necrosis factor-α gene expression along with CD8+ T cells number. Also, NCTD augmented Sora attenuation activity against TAA-induced angiogenesis and metastasis by decreasing VEGFA, HIF-1α, serum lactate dehydrogenase enzyme, and vimentin levels. The combined use of NCTD/Sora suppressed drug resistance and stemness by downregulating ATP-binding cassette subfamily G member 2, neurogenic locus notch homolog protein, spalt-like transcription factor 4, and CD133. NCTD boosted Sora antiproliferative and apoptotic activities by decreasing Ccnd1 and BCL2 expressions along with increasing BAX and caspase-3 expressions. To our knowledge, this study represents the first study providing evidence for the potential novel therapeutic use of NCTD/Sora combination for HCC. Moreover, no previous studies have reported the effect of NCTD on FGL1. [ABSTRACT FROM AUTHOR]

Sepsis‐induced acute kidney injury (SI‐AKI) causes renal dysfunction and has a high mortality rate. Protein arginine methyltransferase‐1 (PRMT1) is a key regulator of renal insufficiency. In the present study, we explored the potential involvement of PRMT1 in SI‐AKI. A murine model of SI‐AKI was induced by cecal ligation and perforation. The expression and localization of PRMT1 and molecules involved in the transforming growth factor (TGF)‐β1/Smad3 and interleukin (IL)‐6/signal transducer and activator of transcription 3 (STAT3) signaling pathways were detected in mouse kidney tissues by western blot analysis, immunofluorescence, and immunohistochemistry. The association of PRMT1 with downstream molecules of the TGF‐β1/Smad3 and IL‐6/STAT3 signaling pathways was further verified in vitro in mouse renal tubular epithelial cells. Cecal ligation and perforation caused epithelial–mesenchymal transition, apoptosis, and inflammation in renal tissues, and this was alleviated by inhibition of PRMT1. Inhibition of PRMT1 in SI‐AKI mice decreased the expression of TGF‐β1 and phosphorylation of Smad3 in the renal cortex, and downregulated the expression of soluble IL‐6R and phosphorylation of STAT3 in the medulla. Knockdown of PRMT1 in mouse renal tubular epithelial cells restricted the expression of Cox‐2, E‐cadherin, Pro‐caspase3, and phosphorylated Smad3 (involved in the TGF‐β1‐mediated signaling pathway), and also blocked IL‐6/soluble IL‐6R, inducing the expression of Cox‐2 and phosphorylated‐STAT3. In conclusion, our findings suggest that inhibition of PRMT1 mitigates SI‐AKI by inactivating the TGF‐β1/Smad3 pathway in the cortex and the IL‐6/STAT3 pathway in the medulla. Our findings may aid in the identification of potential therapeutic target molecules for SI‐AKI. [ABSTRACT FROM AUTHOR]

Inflammation, characterized by the overexpression of IL-6 in various tissues, has been reported as a symptom of coronavirus disease 2019. In this study, we established an experimental system for overexpression of IL-6 in HeLa cells stimulated by TNF-α and IL-17, along with identification of anti-inflammatory materials and components from local agricultural, forestry, and fishery resources. We constructed a library of extracts from natural sources, of which 111 samples were evaluated for their anti-inflammatory activities. The MeOH extract of Golden Berry (Physalis peruviana L) leaf was found to exhibit strong anti-inflammatory properties (IC50 = 4.97 μg/mL). Preparative chromatography identified two active constituents, 4β-hydroxywithanolide E (4β-HWE) (IC50 = 183 nM) and withanolide E (WE) (IC50 = 65.1 nM). Withanolides are known anti-inflammatory ingredients of Withania somnifera, an Ayurvedic herbal medicine. P. peruviana leaves containing 4β-HWE and WE should be considered as useful natural resources for anti-inflammatory products. Withanolides in golden berry leaf extracts inhibit IL-6 overexpression induced by IL-17 and TNF-α in HeLa cells. [ABSTRACT FROM AUTHOR]

Oxidative stress and autophagy are potential mechanisms associated with cerebral ischemia/reperfusion injury (IRI) and is usually linked to inflammatory responses and apoptosis. Curcumin has recently been demonstrated to exhibit anti-inflammatory, antioxidant, anti-apoptotic and autophagy regulation properties. However, mechanism of curcumin on IRI-induced oxidative stress and autophagy remains not well understood. We evaluated the protective effects and potential mechanisms of curcumin on cerebral microvascular endothelial cells (bEnd.3) and neuronal cells (HT22) against oxygen glucose deprivation/reoxygenation (OGD/R) in vitro models that mimic in vivo cerebral IRI. The cell counting kit-8 (CCK-8) and lactate dehydrogenase (LDH) activity assays revealed that curcumin attenuated the OGD/R-induced injury in a dose-specific manner. OGD/R induced elevated levels of inflammatory cytokines TNF-α, IL-6 as well as IL-1β, and these effects were notably reduced by curcumin. OGD/R-mediated apoptosis was suppressed by curcumin via upregulating B-cell lymphoma-2 (Bcl-2) and downregulating Bcl-associated X (Bax), cleaved-caspase3 and TUNEL apoptosis marker. Additionally, curcumin increased superoxide dismutase (SOD) and glutathione (GSH), but suppressed malondialdehyde (MDA) and reactive oxygen species (ROS) content. Curcumin inhibited the levels of autophagic biomarkers such as LC3 II/LC3 I and Beclin1. Particularly, curcumin induced p62 accumulation and its interactions with keap1 and promoted NF-E2-related factor 2 (Nrf2) translocation to nucleus, accompanied by increased NADPH quinone dehydrogenase (Nqo1) and heme oxygenase 1 (HO-1). Treatment of curcumin increased phosphorylationphosphatidylinositol 3 kinase (p-PI3K) and p-protein kinase B (p-AKT). The autophagy inhibitor 3-methyladenine (3-MA) activated the keap-1/Nrf2 and PI3K/AKT pathways. This study highlights the neuroprotective effects of curcumin on cerebral IRI. [ABSTRACT FROM AUTHOR]

Copyright of Cukurova Medical Journal / Çukurova Üniversitesi Tip Fakültesi Dergisi is the property of Cukurova University, Faculty of Medicine and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

PURPOSE: To assess the change of interleukin-6 (IL-6) levels in tears and ocular clinical parameters in corneal ulcer patients with moderate-to-severe infection after adjunctive therapy with platelet-rich fibrin (PRF) lysate-eyedrops compared with autologous serum eyedrops. MATERIALS AND METHODS: This study was a randomized double-blind controlled trial, which compared two groups of patients at Dr. Sardjito Hospital, Yogyakarta. A total of 42 patients (42 eyes) were divided into the control group (21 patients) and the intervention group (21 patients). All patients received antibacterial/antifungal therapy based on the etiology, and an adjunctive eyedrop therapy: autologous serum eyedrops for the control group and PRF lysate eyedrops for the intervention group. The IL-6 levels and clinical changes in patients, such as the area of corneal defects, pericorneal injection, and the level of blepharospasm were measured at the baseline, day 6, and day 13 after starting the treatment. RESULTS: Compared to baseline, the mean IL-6 level in day 13 decreased by 426.6 ± 665.4 pg/ ml (P = 0.005) and 1283.7 ± 1569.1 pg/ml (P = 0.079) in the intervention and control groups, respectively. However, the difference between the two groups was not statistically significant (P = 0.164). In term of corneal defect area, there was a significant decrease at day 6 and day 13 in both groups but there was no statistically significant difference between the two groups in all time points. Similarly, the proportion of blepharospasm and pericorneal injection severity appeared to improve especially on day 13 in both groups but were not statistically different between the two. CONCLUSION: There was a statistically significant decrease in IL-6 levels in the tears in patient using PRF lysate, but there was no significant difference when compared to those using autologous serum. The difference in defect area, degree of blepharospasm, and pericorneal injection was not statistically significant between the two treatment options. [ABSTRACT FROM AUTHOR]

• Previous studies reported that intravenous dexmedetomidine use decreased adverse neurocognitive outcomes in adults undergoing cardiovascular surgery. • The effects of dexmedetomidine use on the brain and inflammatory markers have been unclear in children with congenital heart disease, although several randomized controlled trials have been reported since 2017. • We performed a systematic review and meta-analysis of randomized controlled trials that assessed the effects of dexmedetomidine on the brain and inflammatory markers in pediatric cardiac surgery. • A total of seven randomized controlled trials with 579 children who received cardiac surgeries were included in the meta-analysis. • Intravenous dexmedetomidine use reduced brain markers (neuron-specific enolase, S-100β protein) and an inflammatory marker (interleukin-6) within 24 hours after pediatric cardiac surgery. Dexmedetomidine use decreases adverse neurocognitive outcomes in adults undergoing cardiovascular surgery, but its effect has been unclear in children with congenital heart disease. The authors conducted a systematic review using the PubMed, Embase, and Cochrane Library databases for randomized controlled trials (RCTs) that compared intravenous dexmedetomidine with normal saline during pediatric cardiac surgery under anesthesia. Published randomized controlled trials that evaluated children aged <18 years who underwent congenital heart surgery were included. Nonrandomized trials, observational studies, case series and case reports, editorials, reviews, and conference papers were excluded. The quality of the included studies was assessed using the Cochrane revised tool for assessing risk-of-bias in randomized trials. Meta-analysis was performed to estimate the effects of intravenous dexmedetomidine on brain markers (neuron-specific enolase [NSE], S-100β protein) and inflammatory markers (interleukin-6, tumor necrosis factor [TNF]-α, nuclear factor kappa-B [NF-κB]) during and after cardiac surgery, using random-effect models for standardized mean difference (SMD). Seven RCTs involving 579 children were eligible for the following meta-analyses. Most children underwent cardiac surgery for atrial or ventricular septum defects. Pooled analyses (5 treatment groups in 3 RCTs with 260 children) showed that dexmedetomidine use was associated with reduced serum levels of NSE (pooled SMD, −0.54; 95% CI, −0.96 to −0.12) and S-100β (pooled SMD, −0.85; 95% CI, −1.67 to −0.04) within 24 hours after the surgery. Also, dexmedetomidine use was associated with reduced levels of interleukin-6 (pooled SMD, −1.55; 95% CI, −2.82 to −0.27; 4 treatment groups in 2 RCTs with 190 children). In contrast, the authors observed similar levels of TNF-α (pooled SMD, −0.07; 95% CI, −0.33 to 0.19; 4 treatment groups in 2 RCTs with 190 children) and NF-κB (pooled SMD, −0.27; 95% CI, −0.62 to 0.09; 2 treatment groups in 1 RCT with 90 children) between the dexmedetomidine and control groups. The authors' findings support the effect of dexmedetomidine on reductions in brain markers among children who undergo cardiac surgery. Further studies would be needed to elucidate its clinically meaningful effects using cognitive functions in the long term, and its effects among children who undergo more complex cardiac surgeries. [ABSTRACT FROM AUTHOR]

Objective: To determine the association between olfactory function and cognition in patients and rodents. Background: Perioperative neurocognitive disorders include delayed neurocognitive recovery (dNCR). The contribution of olfactory function to dNCR remains undetermined. It is unknown whether odor enrichment could mitigate dNCR. Methods: We performed a prospective observational cohort study to determine potential association between olfactory impairment and dNCR in patients. We assessed the effects of anesthesia/surgery on olfactory and cognitive function in mice using the block test and Barnes maze. We measured interleukin-6 (IL-6), olfactory mature protein, growth-associated protein 43, mature and premature olfactory neurons, postsynaptic density 95, and synaptophysin in blood, nasal epithelium, and hippocampus of mice. Odor enrichment, IL-6 antibody, and knockout of IL-6 were used in the interaction experiments. Results: Patients with dNCR had worse odor identification than the patients without dNCR [preoperative: 7 (1.25, 9) vs 10 (8, 11), median (interquartile range), P <0.001; postoperative: 8 (2.25, 10) vs 10 (8, 11), P <0.001]. Olfactory impairment associated with dNCR in patients before and after adjusting age, sex, education, preoperative mini-mental state examination score, and days of the neuropsychological tests. Anesthesia/surgery induced olfactory and cognitive impairment, increased levels of IL-6 in blood and nasal epithelium, decreased amounts of olfactory receptor neurons and their markers in the nasal epithelium, and reduced amounts of synapse markers in the hippocampus of mice. These changes were attenuated by odor enrichment and IL-6 antibody. Conclusion: The anesthesia/surgery-induced olfactory impairment may contribute to dNCR in patients and postoperative cognitive impairment in mice. Odor enrichment could be a potential intervention. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The aim of this study was to determine the association of inflammation and immune responses with the outcomes of patients at various stages, and to develop risk stratification for improving clinical practice and reducing mortality. PATIENTS AND METHODS: We included 77 patients with primary outcomes of either death or survival. Demographics, clinical features, comorbidities, and laboratory tests were compared. Linear, logistic, and Cox regression analyses were performed to determine prognostic factors. RESULTS: The average age was 59 years (35-87 years). There were 12 moderate cases (16.2%), 42 severe cases (54.5%), and 23 critical cases (29.9%); and 41 were male (53.2%). Until March 20, 68 cases were discharged (88.3%), and nine critically ill males (11.7%) died. Interleukin-6 (IL-6) levels on the 1st day were compared with IL-6 values on the 14th day in the severe and the critically ill surviving patients (F=4.90, p=0.034, ß=0.35, 95% CI: 0.00-0.10), and predicted death in the critically ill patients (p=0.028, ß=0.05, OR: 1.05, 95% CI: 1.01-1.10). CD4+ T-cell counts at admission decreased the hazard ratio of death (p=0.039, ß=-0.01, hazard ratio=0.99, 95% CI: 0.98-1.00, and median survival time 13.5 days). CONCLUSIONS: The present study demonstrated that IL-6 levels and CD4+ T-cell count at admission played key roles of predictors in the prognosis, especially for critically ill patients. High levels of IL-6 and impaired CD4+ T-cells are seen in severe and critically ill patients with COVID-19. [ABSTRACT FROM AUTHOR]

Objectives Precise and early diagnosis of neonatal asphyxia may improve outcomes. Recent studies aim to identify diagnostic biomarkers in neonates at risk for brain damage. The current study was designed to evaluate the diagnostic value of new biomarkers for neonatal asphyxia. Materials & Methods This prospective study was conducted with an available sampling of infants upper 35 weeks of gestational age, including neonates with asphyxia (case group) and healthy controls, 2014-2022, in Ghaem Hospital, Mashhad, Iran. Data collection was performed utilizing a researcher-made questionnaire, including maternal and neonatal characteristics, as well as clinical and laboratory evaluation. Serum umbilical cord levels of interleukin-6 (IL6), interleukin-1-beta (IL-1β), pro-oxidant-antioxidant balance (PAB), and heat shock protein-70 (HSP70), as well as nucleated red blood cells count (NRBC), were determined. Data were analyzed by t-test, Chi-square, receiver operating characteristic (ROC), and regression models. Results The differences in variables IL6, IL1β, PAB, NRBC/100WBC, and HSP70 were statistically significant between the two groups (in all cases, P<0.0001). In the diagnosis of asphyxia, the most sensitive marker (89%) was IL1β more than 2.39 pg/ml and HSP 70 upper than 0.23 ng/ml, while IL6 was higher than 9pg/ml, determined as the most specific marker (85%). Furthermore, a combination of HSP + PAB and IL6 + lL1b + PAB + NRBC/100WBC possesses the prediction power of 93.2% and 87.3%, respectively, for diagnosing asphyxia. Conclusion According to data analysis, the combination of new biochemical markers (NRBC count, IL6, IL1β, PAB, and HSP 70) could be a reliable marker for diagnosing infants with asphyxia. [ABSTRACT FROM AUTHOR]

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Increased incidence of postoperative cognitive dysfunction (POCD) is observed in elderly patients underwent intravenous anesthesia (TIVA) with endotracheal intubation. Modulation of anesthetics compatibility may reduce the severity of POCD. Elderly patients scheduled for TIVA with endotracheal intubation were randomly divided into the control group (1.00-2.00 mg/kg propofol) and the etomidate and propofol combination group (1.00-2.00 mg/kg propofol and 0.30 mg/kg etomidate). Serum cortisol, S100ß, and neuron-specific enolase (NSE), interleukin (IL)-6, and IL-10 were monitored during or after the operation. Mini-mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were utilized to assess the severity of POCD. 63 elderly patients in the etomidate and propofol combination group and 60 patients in the control group were enrolled, and there was no significant difference in gender, American Society of Anesthesiologists (ASA) physical status, surgical specialty, intraoperative blood loss, and operation time between the two groups. Significantly increased serum cortisol, S100ß, NSE, IL-6, and reduced MMSE and MoCA scores were detected in the control group at different time points after the operation (0-72 h post operation) when compared to those before the operation. Similar trends for these observed factors were found in the etomidate and propofol combination group. In addition, the etomidate and propofol combination group showed better effects in reducing the serum levels of cortisol, S100ß, NSE, IL-6, and increasing the MMSE and MoCA scores when compared to the control group. The present study demonstrates that the combination of propofol with etomidate could alleviate POCD in elderly patients underwent TIVA with endotracheal intubation anesthesia. [ABSTRACT FROM AUTHOR]

Silicosis is an occupational lung disease caused by inhaling silica dust. The disease is characterized by early lung inflammation and late irreversible pulmonary fibrosis. Here we report the effect of Baicalin, a main flavonoid compound from the roots of Chinese herbal medicine Huang Qin on silicosis in a rat model. Results showed Baicalin (50 or 100 mg/kg/day) can mitigate the silicainduced lung inflammation and reduce the harm of alveolar structure and the blue region of collagen fibers in rat lung at 28 days after administration. At the same time, Baicalin also diminished the level of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-a (TNF-a) and transforming growth factor-ß1 (TGF-ß1) in lung tissues. The protein expression of collagen I (Col-1), a-smooth muscle actin (a-SMA) and vimentin were down-regulated while E-cadherin (E-cad) was increased in Baicalin-treated rats. In addition, the Toll Like Receptor 4 (TLR4)/nuclear factor kappaB (NF-κB) pathway was enabled at 28 days after silica infusion, and the treatment of Baicalin diminished the expression of TLR4 and NF-κB in the lungs of rat with silicosis. These results suggested that Baicalin inhibited the pulmonary inflammatory and fibrosis in a rat model of silicosis, which could be attributed to inhibition of the TLR4/NF-κB pathway. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The aim of this study was to discuss the prognostic significance of peripheral interleukin-6 (IL-6) and CD4+ and CD8+ T cells in COVID-19. PATIENTS AND METHODS: Eighty-four COVID-19 patients were retrospectively analyzed and classified into three groups, including the moderate group (15 cases), the serious group (45 cases), and the critical group (24 cases). The levels of peripheral IL-6, CD4+, and CD8+ T cells and CD4+/CD8+ were determined for each group. It was assessed whether these indicators were correlated to the prognosis and death risks of COVID-19 patients. RESULTS: The three groups of COVID-19 patients differed significantly in the levels of peripheral IL-6 and CD4+ and CD8+ cells. The IL-6 levels in the critical, moderate, and serious groups were increased successively, but the changed levels of CD4+ and CD8+ T cells were just opposite to that of IL-6 (p<0.05). The peripheral IL-6 level increased dramatically in the death group, while the levels of CD4+ and CD8+ T cells decreased significantly (p<0.05). The peripheral IL-6 level was significantly correlated with the level of CD8+ T cells and CD4+/CD8+ ratio in the critical group (p<0.05). The logistic regression analysis indicated a dramatic increase in the peripheral IL-6 level in the death group (p=0.025). CONCLUSIONS: The aggressiveness and survival of COVID-19 were highly correlated with the increases in IL-6 and CD4+/CD8+ T cells. The fatalities of COVID-19 individuals remained at increased incidence due to elevated peripheral IL-6 levels. [ABSTRACT FROM AUTHOR]

Objectives: The coronavirus pandemic was associated with a high mortality rate in the Republic of North Macedonia. Finding early markers of the disease's severity may predict outcomes and guide the treatment of the disease. The aim of our study was to evaluate the role of inflammatory markers in predicting the outcome of COVID-19 in hospitalized patients. Methods: The study included 104 PCR-confirmed COVID-19 patients who underwent hospital treatment at the Institute of Lung Diseases and Tuberculosis in Skopje, North Macedonia, between November 2020 and May 2021. Inflammatory markers were assessed in all patients and correlated with the disease severity and outcome in terms of survival or death. Results: IL-6 and LDH at admission were significantly elevated in patients with a severe or critical form of the disease and among non-survivors. In addition, IL-6 showed 87.9% of sensitivity and 61.8% of specificity for distinguishing non-survivors from survivors with a cut-off value of 21.7 pg/ml in the receiver operator curve (ROC). Procalcitonin was significantly increased in non-survivors. Parallel to the increase of disease severity, the values of CRP and LDH increased significantly during hospitalization. Conclusion: The results of the study indicate that a significant association exists between the highly increased levels of CRP, LDH, IL-6 and procalcitonin and the severity of the disease and mortality in COVID-19 patients. Their measurements and follow-up during the course of the disease could be used as predictors for prognosis and outcome but also as a subject for targeted therapy. [ABSTRACT FROM AUTHOR]

Deep tooth decay approaching the pulp may develop into pulpitis; to prevent this, pulp cells need to balance the rapid immune response to avoid rapid swelling of the pulp. Current treatment of deep decay that approaches the pulp involves the application of drugs that induce low‐level inflammation in the dental pulp to promote its repair, but this treatment is sometimes insufficient. However, the unsuccessful treatment often resulted in pulpitis. The C5a‐C5aR is the initial stage of the immune cascade response. Blocking the binding of C5a‐C5aR can slow the immune response in the narrow pulp cavity, so that dental pulp cells have enough time to proliferate, migrate, and differentiate. In this study, we compared lipoteichoic acid (LTA) and lipopolysaccharides (LPS) at different concentrations and time points and used the C5aR antagonist W54011 to block the C5a‐C5aR axis. The blocking effect was detected by analyzing the expression of C5a, C5aR, interleukin (IL)‐6, and Toll‐like receptors 2 and 4 (TLR‐2, 4). Next, we determined the optimal concentration and duration of LTA and LPS treatment in combination with W54011. Based on our results, we selected 1.0 μg·mL−1 LPS treatment for 48 h to generate an inflammatory model of human dental pulp cells. We then regrouped the cells and conducted expression analyses to monitor the expression of C5a, C5aR, IL‐6, and TLR‐4 at the protein and mRNA levels. LPS stimulation for 48 h and treatment with W54011 for 48 h effectively inhibited inflammation and did not affect C5a expression. This study provides a basis for follow‐up studies of W54011 in dental pulp cells. [ABSTRACT FROM AUTHOR]

Background: Frailty can increase adverse health outcomes in older adults. Progranulin is a secreted glycoprotein involved in regulating various biological processes. Different perspectives exist on the relationship between progranulin and frailty. Aims: We aimed to evaluate the association of progranulin with frailty in older Chinese adults. Methods: We included 265 older in-patients who were divided into the robust (n = 31), pre-frail (n = 116) and frail (n = 118) groups according to the FRAIL scale. Serum IL-6, CXCL-10, progranulin, and CRP levels were assayed. Spearman's correlation and logistic regression models were used to analyze the association of serum biomarkers with frailty, and ROC was used to evaluate the diagnostic progranulin value for frailty. Results: The frail group was older and had lower BMI, higher prevalence of coronary heart disease, worse grip strength and walking speed, and higher IL-6, CXCL-10, progranulin, and CRP serum levels than the robust and pre-frail groups. Progranulin levels were negatively correlated with grip strength (r = − 0.152, p = 0.016) and positively correlated with IL-6 (r = 0.207, p = 0.001) and CXCL-10 (r = 0.160, p = 0.009) after adjusting for age and sex. Furthermore, progranulin remained associated with frailty after adjusting for age, sex, BMI, smoking, chronic diseases, and pro-inflammatory cytokines (OR = 1.003, 95% CI 1.001–1.006, p = 0.022). The AUC of serum progranulin levels for diagnostic frailty was 0.927 (95% CI 0.896–0.958, p < 0.001). Conclusion: High serum progranulin levels were observed in frail older adults and were associated with worse physical function and increased chronic inflammation. Progranulin may be a potential biomarker for frailty. [ABSTRACT FROM AUTHOR]

The incidence of non-alcoholic steatohepatitis (NASH) is dramatically increasing, but the effect of NASH on colon cancer liver metastasis (CLM) is controversial. The aim of this study was to investigate the impact and mechanism of action of NASH on CLM using a western diet (WD)-fed mouse model. Six-week-old male C57BL/6 J mice were used. They were divided into the WD group and control group with normal diet. MC38 colon cancer cells were injected into the spleen at 2, 6, 8 and 16 weeks, and mice were killed at 2 weeks after injection to evaluate hepatic steatosis, fibrosis, metastasis and mRNA/protein expression in the liver. Only mice fed a WD for 16 weeks showed hepatic fibrosis. These mice showed significantly higher alanine aminotransferase and total cholesterol levels compared with the control group (p < 0.05). The WD group showed significantly lower tumor number and smaller tumor diameter (p < 0.05). In the WD group, expression of SAA1 , IL6 , STAT3 and MMP9 mRNA in the liver was significantly lower than in the control group (p < 0.05). Serum amyloid A1 protein expression was also lower in the WD group. The WD-fed NASH mouse model showed an inhibitory effect on CLM. Suppressed interleukin-6/signal transducer and activator of transcription 3 signaling and serum amyloid A/matrix metalloproteinase 9 expression may affect this phenomenon. [ABSTRACT FROM AUTHOR]

Exopolysaccharides (EPS) derived from lactic acid bacteria have received considerable attention because of their diverse bioactivities and high safety. In our previous work, a crude EPS produced by Lactiplantibacillus plantarum Z-1 under H 2 O 2 stress and its three purified fractions were prepared and characterized. In the present work, antioxidant and anti-inflammatory activities of these EPSs were investigated. The four EPSs were found to possess considerable free radical scavenging activity, and be able to decrease the ROS and MDA levels in H 2 O 2 -induced oxidative stress RAW 264.7 macrophages, and increase the activities of SOD and CAT enzymes. It is likely that activating Nrf2/HO-1 signaling pathway is one of their important antioxidant mechanisms. These EPSs were also found to effectively reduce the secretion of inflammatory mediators, such as pro-inflammatory factors (TNF-α, IL-1β, IL6) and NO, and increase the release of anti-inflammatory factor IL-10. The anti-inflammatory effect of EPSs could be due to their ability to inhibit the activation of NF-κB/TLR4 signaling pathway and intracellular COX-2 signaling cascade. Therefore, these EPS fractions have good antioxidant and anti-inflammatory activities, providing useful enlightenment for the application of these EPSs in functional foods and medicines. • EPSs from L. plantarum Z-1 had marked protective effects on cellular oxidative stress. • EPSs exhibited considerable anti-inflammatory activity in LPS-induced RAW264.7 cells. • Activating Nrf2/HO-1 signaling pathway could be the important antioxidant mechanism. • Inhibition on NF-κB/TLR4 and COX-2 pathways could be the anti-inflammatory mechanism. [ABSTRACT FROM AUTHOR]

• Preeclampsia is characterized by gestational hypertension and end-organ dysfunction. • Some women with preeclampsia develop lethal complications such as eclampsia. • The pathogenesis of the disease and its complications is not completely understood. • Severe disease is associated with increased pro-inflammatory cytokines in plasma. • These biomarkers may play an important role as disease driver of preeclampsia. To assess whether plasma concentrations of the circulating inflammatory proteins Interleukin-6 (IL-6), Vascular Cell Adhesion Molecule-1 (VCAM-1) and C-Reactive Protein (CRP) are increased in women with preeclampsia with end-organ complications, compared with women with preeclampsia without end-organ complications. We used samples from a large prospective biobank collection (Preeclampsia Obstetric Adverse Event biobank), and two large, randomized preeclampsia therapeutic treatment trials. All samples were collected in Cape Town, South Africa. The last plasma sample collected prior to birth was analyzed for IL-6, VCAM-1 and CRP concentrations. We categorized cases according to disease severity and compared circulating levels of these analytes. Covariate adjustment was performed. 183 women were included. Compared with women without end-organ complications (n = 119), those with preeclampsia with two or more end-organ complications (n = 15) had a 4.9-fold (95 % CI, 1.81–13.09, p = 0.001) increase in IL-6 and a 1.7-fold (95 % CI, 1.11–2.72, p = 0.012) increase in VCAM-1 plasma concentrations. Comparing women with two or more end-organ complications to those with one end-organ complication (n = 49), plasma concentrations of IL-6 were 3.2-fold (95 % CI, 1.18–8.39, p = 0.018) increased, while there was no statistically significant difference for VCAM-1 (1.2-fold higher, 95 % CI, 0.79–1.91, p = 0.50). Plasma concentrations of CRP did not differ between the groups. Plasma concentrations of IL-6 and VCAM-1, but not CRP, were increased among women with preeclampsia and end-organ complications, compared with women without end-organ complications. IL-6 and VCAM-1 could be drivers of disease in preeclampsia and potentially useful to identify women at high risk of severe disease. [ABSTRACT FROM AUTHOR]

The aim of this study was to explore the association between phthalates (PAEs) exposure and all-cause mortality among diabetic cases, and potential molecular mechanisms of the effect. We followed 2806 diabetes cases from 2008 to the end of 2018 based on the Dongfeng-Tongji study, of which 446 cases died. We measured serum levels of six PAEs (DMP, DEP, DiBP, DnBP, BBP, and DEHP). Cox models were used to investigate the associations between PAEs and all-cause mortality. Genes related to PAEs are obtained from the Comparative Toxicogenomics Database. We constructed polygenic scores for sex hormone-binding globulin (SHBG) and testosterone, and functional SNPs for IL-6 , PPARG , and GPX1 from genotyping data, and further analyzed the environment-gene interactions. The positive associations of PAEs (DMP, DiBP, DnBP, DEHP) with mortality were only observed in males but not in females. Comparing with the extreme quartile 1, the HRs (95% CI) for quartile 4 were 1.63 (0.17, 2.26) for DMP, 1.82 (1.29, 2.56) for DiBP, 1.68 (1.18, 2.40) for DnBP, 1.66 (1.17, 2.36) for DEHP. Enrichment analysis showed that PAEs-related genes were mainly associated with hormones and IL-6-related pathways. Genetic variants of SHBG, testosterone, and IL-6 modified the association between PAEs mixture and all-cause mortality. PAEs exposure are associated with all-cause mortality among diabetic cases, and PAE exposure increases the risk of all-cause mortality only in males. Effects on the hormonal system and IL6-related pathways may be potential mechanisms. [Display omitted] • Exploring the associations between PAEs and mortality in a cohort of diabetes cases. • Exposure to PAEs is associated with an elevated risk of death in males with diabetes. • PAEs-related genes mainly linked to hormonal and IL-6-related pathways. • SHBG , testosterone , IL-6 variants modify PAEs-mortality association in diabetes cases. [ABSTRACT FROM AUTHOR]

Immunoglobulin A (IgA) is involved in the maintenance of gut homeostasis. Although the oral administration of bifidobacteria increases the amount of fecal IgA, the effects of bifidobacteria on intestinal immunity remain unclear. We found and characterized membrane vesicles (MVs) derived from Bifidobacterium longum subsp. infantis toward host immune cells. Bifidobacterium infantis MVs consisted of a cytoplasmic membrane, and extracellular solute-binding protein (ESBP) was specifically detected. In the presence of B. infantis MVs or recombinant ESBP, RAW264 cells produced the pro-inflammatory cytokine IL-6. IgA was produced by Peyer's patches cells following the addition of B. infantis MVs. Therefore, ESBP of B. infantis MVs is involved in the production of IgA by acquired immune cells via the production of IL-6 by innate immune cells. [ABSTRACT FROM AUTHOR]

Objectives Precise and early diagnosis of neonatal asphyxia may improve outcomes. Recent studies aim to identify diagnostic biomarkers in neonates at risk for brain damage. The current study was designed to evaluate the diagnostic value of new biomarkers for neonatal asphyxia. Materials & Methods This prospective study was conducted with an available sampling of infants upper 35 weeks of gestational age, including neonates with asphyxia (case group) and healthy controls, 2014-2022, in Ghaem Hospital, Mashhad, Iran. Data collection was performed utilizing a researcher-made questionnaire, including maternal and neonatal characteristics, as well as clinical and laboratory evaluation. Serum umbilical cord levels of interleukin-6 (IL6), interleukin-1-beta (IL- 1β), pro-oxidant-antioxidant balance (PAB), and heat shock protein-70 (HSP70), as well as nucleated red blood cells count (NRBC), were determined. Data were analyzed by t-test, Chi-square, receiver operating characteristic (ROC), and regression models. Results The differences in variables IL6, IL1β, PAB, NRBC/100WBC, and HSP70 were statistically significant between the two groups (in all cases, P<0.0001). In the diagnosis of asphyxia, the most sensitive marker (89%) was IL1β more than 2.39 pg/ml and HSP 70 upper than 0.23 ng/ml, while IL6 was higher than 9pg/ml, determined as the most specific marker (85%). Furthermore, a combination of HSP + PAB and IL6 + lL1b + PAB + NRBC/100WBC possesses the prediction power of 93.2% and 87.3%, respectively, for diagnosing asphyxia. Conclusion According to data analysis, the combination of new biochemical markers (NRBC count, IL6, IL1β, PAB, and HSP 70) could be a reliable marker for diagnosing infants with asphyxia. [ABSTRACT FROM AUTHOR]

The signaling mechanisms for Porphyromonas gingivalis lipopolysaccharide (PgLPS)-induced inflammation in human dental pulp cells are not fully clarified. This in vitro study aimed to evaluate the involvement of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway in PgLPS-induced pulpal inflammation. Human dental pulp cells (HDPCs) were challenged with PgLPS with or without pretreatment and coincubation with a PI3K/Akt inhibitor (LY294002). The gene or protein levels of PI3K, Akt, interleukin (IL)-6, IL-8, alkaline phosphatase (ALP), osteocalcin and osteonectin were analyzed by reverse transcription polymerase chain reaction (PCR), real-time PCR, western blotting, and immunofluorescent staining. In addition, an enzyme-linked immunosorbent assay was used to analyze IL-6 and IL-8 levels in culture medium. In response to 5 μg/ml PgLPS, IL-6, IL-8, and PI3K, but not Akt mRNA expression of HDPCs, was upregulated. IL-6, IL-8, PI3K, and p-Akt protein levels were stimulated by 10–50 μg/ml of PgLPS in HDPCs. PgLPS also induced IL-6 and IL-8 secretion at concentrations higher than 5 μg/ml. Pretreatment and co-incubation by LY294002 attenuated PgLPS-induced IL-6 and IL-8 mRNA expression in HDPCs. The mRNA expression of ALP, but not osteocalcin and osteonectin, was inhibited by higher concentrations of PgLPS in HDPCs. P. gingivalis contributes to pulpal inflammation in HDPCs by dysregulating PI3K/Akt signaling pathway to stimulate IL-6 and IL-8 mRNA/protein expression and secretion. These results are useful for understanding the pulpal inflammation and possible biomarkers of inflamed pulp diagnosis and treatment. [ABSTRACT FROM AUTHOR]

It was reported that lncRNAs have an effect on immune-related diseases, however, their roles in periodontitis remain to be investigated. The aim of this study was to look for immune-related lncRNAs in periodontitis, and to preliminarily explore their function in vitro. CIBERSORT was used to analyze abundance of immune cell in the periodontal tissue. Correlation between the expression profile of lncRNAs and abundance of immune cell was calculated and immune-related lncRNAs were identified. The expressions of immune-related lncRNAs identified were validated by RT-qPCR with 15 periodontitis and 15 healthy gingival tissues. The expressions of PRKCQ-AS1 and EGOT in HGFs were detected under the stimulation of different concentrations of TNF-α (0, 10, 15, 20, 30 ng/mL) and different duration (0, 12, 24 and 48 h). Then, siRNA was used to silence PRKCQ-AS1 and EGOT in HGFs. The expression level of IL-1β, IL-6, IL-8 of the HGFs after stimulated by 15 ng/mL TNF-α, and the activation of NF-κB pathway was observed. PRKCQ-AS1 and EGOT were identified as top 2 immune-related lncRNAs in periodontal tissues. The expressions of PRKCQ-AS1 and EGOT were significantly up-regulated in inflamed periodontal tissue and in HGFs under TNF-α stimulation. After knock-down of PRKCQ-AS1 and EGOT, expression level of IL-1β, IL-6, and IL-8 in HGFs with TNF-α stimulation were decreased, and activation of NF-κB pathway was inhibited. PRKCQ-AS1 and EGOT were firstly identified as immune-related lncRNAs in periodontal tissue, and they regulate the expression of IL-1β, IL-6, and IL-8 of HGFs through the NF-κB pathway. [ABSTRACT FROM AUTHOR]

Interleukin-6 (IL-6) contributes to the regulation of functions in various tissues and organs. Even though IL-6 has been reported to modulate bone metabolism in previous studies, this finding is controversial. This study aims to evaluate the possible involvement of IL-6 in bone metabolism by examining the histological activity of osteoblasts and osteoclasts in the femora of Il-6 deficient (Il-6 −/− ) mice. Eight-week-old male Il-6 −/− mice and their wild-type littermates were fixed with a paraformaldehyde solution, and their femora were extracted for micro-CT analysis, immunohistochemistry, and real-time PCR analysis. Il-6 −/− femora showed an increased bone volume/tissue volume (TV) but a reduced bone mineral density compared with the wild-type. Furthermore, the tissue-nonspecific alkaline phosphatase positive area/TV ratio, the expression of Runx2 , Osterix , and Rankl , and the number of tartrate-resistant acid phosphatase-positive osteoclasts were all increased in the Il-6 −/− mice. A considerable number of unmineralized areas within the bone matrix and abundant sclerostin-reactive osteocytes were observed in Il-6 −/− femoral metaphyses but not in the wild-type. Interestingly, the gene expression of Cd206 was elevated in Il-6 −/− femora, and many F4/80-positive macrophages/monocytes and CD206-immunoreactive macrophages in the primary trabeculae had migrated closer to the growth plate, where intense RANKL immunoreactivity was detected. These results suggest that, in an IL-6-deficient state, CD206-positive macrophages may differentiate into osteoclasts when in contact with RANKL-reactive osteoblastic cells. In a state of IL-6 deficiency, the population and cell activities of osteoblast, osteoclasts, and macrophages seemed to be facilitated, except for the reduced mineralization in bone. [ABSTRACT FROM AUTHOR]

Glycolytic metabolism enzymes have been implicated in the immunometabolism field through changes in metabolic status. PGK1 is a catalytic enzyme in the glycolytic pathway. Here, we set up a high-throughput screen platform to identify PGK1 inhibitors. DC-PGKI is an ATP-competitive inhibitor of PGK1 with an affinity of K d = 99.08 nmol/L. DC-PGKI stabilizes PGK1 in vitro and in vivo , and suppresses both glycolytic activity and the kinase function of PGK1. In addition, DC-PGKI unveils that PGK1 regulates production of IL-1 β and IL-6 in LPS-stimulated macrophages. Mechanistically, inhibition of PGK1 with DC-PGKI results in NRF2 (nuclear factor-erythroid factor 2-related factor 2, NFE2L2) accumulation, then NRF2 translocates to the nucleus and binds to the proximity region of Il-1β and Il-6 genes, and inhibits LPS-induced expression of these genes. DC-PGKI ameliorates colitis in the dextran sulfate sodium (DSS)-induced colitis mouse model. These data support PGK1 as a regulator of macrophages and suggest potential utility of PGK1 inhibitors in the treatment of inflammatory bowel disease. A potent PGK1 antagonist, DC-PGKI, suppresses glycolytic activity and Il-1 β and Il-6 genes through activating NRF2 signaling pathway in LPS-stimulated macrophages. Moreover, DC-PGKI ameliorates acute mouse UC model. [Display omitted] [ABSTRACT FROM AUTHOR]

• The role of KL-6 and IL-6 for predicting mortality in critically ill COVID-19 patients was studied. • Peak KL-6 and IL-6 levels were elevated in deceased COVID-19 patients. • In multivariable analysis, peak KL-6 ≥ 1019.2 U/mL was associated with mortality. • Increase in KL-6 level 1 week after admission was significantly higher in the deceased group. • Serum KL-6 and IL-6 levels could predict mortality in critically ill COVID-19 patients. [ABSTRACT FROM AUTHOR]

The oral mucosa goes through a complicated series of biological healing processes to regain equilibrium after being injured. To heal wounds, we need a material that can heal wounds quickly and well. Cinnamon is widely used for therapy because it has good anti-bacterial, anti-inflammatory, and antioxidant effects. The purpose of this study was to analyze the healing effect of the application of lip balm Cinnamomum on lip incisions based on the level of immunohistochemical interleukin-6. This experimental study was conducted at the laboratory biomedical Faculty of Medicine, Universitas Islam Bandung. A 10 mm length and 4 mm depth incision lip mucous was surgically created in twenty-seven male rats with healthy, 200-300mg of body weight, male, 3-5 months. Animals were divided by simple random sampling were divided into three groups, group 1: the animal treated lip healing with distilled water (control). Group 2: the animal treat lip healing with placebo lip balm, and lastly, group 3: the animal treat lip healing with lip balm Cinnamomum burmannii. Each group performs observation on day-3, 7, and 14. To evaluate the effectiveness of treatment, a lip biopsy performs during each observation time. The immunoexpression IL-6 analysis was assessed by scoring distribution and intensity expression with a Leica microscope. There were significant differences in the level of immunoexpression Interleukin-6 in a group with treatment by lip balm Cinnamomum burmannii. By the time of observation, day 14 of group 2 have a greater level of IL-6 compared with the other groups. Application lip balm Cinnamomum burmanni is effective in faster and good remodeling lip healing process by seen increasing level of IL-6. [ABSTRACT FROM AUTHOR]

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Montmorency Cherry Juice (MCJ) may improve acute exercise recovery by attenuating inflammation and oxidative stress. However, the anti-inflammatory effects of MCJ on monocyte responses following resistance exercise have not been explored. Seven resistancetrained males (age: 22.9 ± 4.1 yrs; height: 1.8 ± 0.1 m; weight: 81.7 ± 13.2 kg) participated in this study. Participants completed a placebo-controlled crossover design, drinking either MCJ or placebo beverages, 7 days prior to completing an acute bout of unilateral resistance exercise. Statistical significance was assessed using a withinsubjects repeated measures ANOVA; alpha level p = 0.05. Main effects for time were observed for changes in classical and intermediate monocytes (p = 0.05), but no significant treatment effects were observed for monocyte subtypes p > 0.05. Classical monocytes (CD14+ CD16-) increased and peaked 24 hr post-exercise (placebo 1.14 ± 0.04 and MCJ 1.06 ± 0.06-fold). Intermediate monocytes peaked 48 hr post-exercise increasing 1.82 ± 0.41 and 2.01 ± 0.80-fold. Nonclassical monocytes peaked post-exercise (placebo 1.17 ± 0.31 and MCJ 1.02 ± 0.20-fold). Peak pain visual analog scale (VAS) occurred post-exercise for MCJ (3.63 ± 2.01-fold) and 72 hr post-exercise for placebo (4.26 ± 3.46-fold). IL-6 and pressure pain threshold (PPT) peaked 24 hr post-exercise (IL-6 placebo 3.83 ± 1.01- and MCJ 6.43 ± 3.43-fold) and (PPT placebo 86.37 ± 3.95% and MCJ 82.81 ± 2.90% of pressure needed at pre-exercise). Our data suggests MCJ consumption does not decrease muscle soreness, IL-6, or monocyte subset responses following a high-intensity resistance exercise protocol in resistance-trained males. [ABSTRACT FROM AUTHOR]

PURPOSE: The objective of this study was to evaluate interleukin-6 (IL-6) tear concentration and clinical outcome in patients with moderate-to-severe bacterial corneal ulcers post autologous platelet-rich plasma (PRP) eye drop therapy. MATERIALS AND METHODS: This was a pre-post designed study involving 21 moderate-severe corneal ulcer patients who got autologous PRP eye drop. Subjects were got autologous PRP eye drop as adjuvant therapy. Patients with moderate-to-severe infectious bacterial corneal ulcers were included in this study. Tear sampling was performed before therapy using sterile Schirmer paper from conjunctival inferior fornix. PRP therapy was performed for 7 days. Data recording and tear sampling were then performed at day 0 (pre-PRP), day 7 (D+7), and day 14 (D+14) after PRP therapy. Data recording included presence of pericorneal injection, blepharospasm, size of corneal defects, and hypopyon. RESULTS: There was a decrease in IL-6 tear concentration by day 14 after PRP therapy (P < 0.001). IL-6 concentration at day 7 after therapy (7525.67 ± 7092 pg/mL) tended to be lower before therapy (10,599 ± 6158 pg/mL), but not statistically significant (P = 0.156). The size of corneal defects decreased significantly post PRP at day 7 (P = 0.035) and at day 14 (P = 0.001). There was a significant blepharospasm at day 7 (P = 0.012) and day 14 (P < 0.001). There was a significant pericorneal injection only at day 14 (P = 0.002). There was no significant decreased hypopyon. CONCLUSION: There was a significant reduction in IL-6 tear concentration and clinical improvement in moderate-to-severe bacterial corneal ulcers which got autologous PRP eye drop as adjuvant therapy. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) have proven clinical benefits in various advanced cancers. However, despite their significant therapeutic efficacy, ICIs induce immune-related adverse events. Among these events, autoimmune meningoencephalitis often has severe effects on patients' outcomes, but its specific clinical features are still unclear. Here, we report two cases of ICI-associated meningoencephalitis with elevated interleukin-6 (IL-6) levels in the cerebrospinal fluid (CSF). A 47-year-old woman (Case 1) with renal cell carcinoma developed severe headache after a seventh nivolumab administration. A neurological examination revealed jolt accentuation signs and hyperreflexia in all extremities. CSF analysis revealed a high IL-6 value (6,620 pg/mL) with marked pleocytosis. A 70-year-old woman (Case 2) who received an initial administration of nivolumab plus ipilimumab for renal cell carcinoma developed alterations of consciousness. She presented with impaired consciousness, neck stiffness, and hyperreflexia in all extremities. CSF analysis demonstrated a high IL-6 value (49.3 pg/mL) with mild pleocytosis. Both patients were treated with steroid pulse therapy (methylprednisolone 1,000 mg/day, 3 days), followed by the administration of oral predonisolone. The symptoms and laboratory findings improved in both cases. CSF IL-6 values were proportional to the severity of meningoencephalitis and other clinical parameters. These findings may help elucidate the mechanisms of central nervous system complications that are caused by ICIs. [ABSTRACT FROM AUTHOR]

Objective: To know the relationship between the occurrence of acute kidney injury (AKI) in patients with sepsis concerning the severity of inflammation. In this study, interleukin-6 (IL-6) and C-reactive protein (CRP) markers represented the severity of inflammation. Furthermore, the researchers wanted to see whether this inflammatory marker in the serum of septic patients in the intensive care unit (ICU) could predict the occurrence of AKI in the future. Design: This study was a prospective cohort nested-case control study, namely a case-control study conducted in a cohort population. Setting: This research has been carried out in the ICU of Dr. Wahidin Sudirohusodo Hospital Makassar and Hasanuddin University Hospital. Serum IL-6 examination was carried out in the Hasanuddin University Hospital laboratory. Patients and participants: This study's samples . were septic patients treated in the ICU of Dr. Wahidin Sudirohusodo Hospital Makassar and Hasanuddin University Hospital Makassar starting from January 2021. The sample selection was carried out consecutively, namely the selection of respondents based on the arrival of patients treated in the ICU until fulfilled. Measurement and results: We used the Mann- Whitney test for data analysis in this study. There was a significant difference in serum IL-6 and CRP levels between the two groups on day 0 and day 3 of ICU admission and changes from day 0 to day 3, whereas changes in CRP levels from day 0 to day 3 were a good predictor of AKI, with a cut-off value of 17.75 mg/l. Conclusions: In this study, CRP and IL-6 levels could be used to predict AKI. IL-6 and CRP had an essential role in the inflammatory response and helped to predict clinical outcomes in patients with AKI. [ABSTRACT FROM AUTHOR]

The detailed clinical course of coronavirus disease 2019 (COVID-19) in patients with hairy cell leukemia (HCL) is rarely reported. We report the first case of HCL diagnosed with prolonged pancytopenia after COVID-19 infection in Japan. We describe the case of a 56-year-old man who was diagnosed with COVID-19. Computed tomography revealed ground-glass opacities in the bilateral lung lobes as well as splenomegaly. Remdesivir and dexamethasone were administered for the treatment of COVID-19. Since the pancytopenia persisted, bone marrow examination was performed, and he was diagnosed with HCL. Although pancytopenia can occur with COVID-19 alone, clinicians should be alerted regarding the presence of hematologic malignancies in patients in whom pancytopenia persists after COVID-19 treatment or in those with splenomegaly. Further, the condition of all previously reported patients with COVID-19 associated with HCL was severe enough to require mechanical ventilation. This is the first case in which the disease was not severe. The interleukin-6 (IL-6) level was lower in this case than in previous cases, suggesting that racial differences in IL-6 production may have contributed to COVID-19 severity. [ABSTRACT FROM AUTHOR]