Increase In Inflammatory Mediators Research Articles

P102 Importance of the inflammation in adipose tissue as exacerbating factor of obesity-associated psoriasis

Abstract Obesity is a risk factor for psoriasis. However, it is not necessarily detrimental when excess fat is stored in healthy adipose tissue. To identify pathogenic association between obesity and psoriasis, we investigated an obese mouse model of psoriasis induced by topical imiquimod or dermal interleukin (IL)-23 injection. Obese mice exhibited aggravated psoriatic dermatitis with pronounced systemic inflammatory responses when exposed to imiquimod. Notably, imiquimod-induced psoriatic dermatitis in obese mice significantly reduced fat mass. Further, pronounced monocyte–macrophage infiltration of perigonadal adipose tissue, increased expression of genes linked to inflammation, and upregulation of cell death-associated molecules were evident in obese mice treated with imiquimod compared with their lean counterparts. In contrast, IL-23 injection could induce similar features of psoriatic inflammation in obese and lean mice, without causing adipose tissue destruction or a systemic increase in inflammatory mediators. Obese adipose tissue of mice with imiquimod-induced psoriatic inflammation featured genetic and epigenetic changes in adipocytes and shifts in macrophage compartments towards disturbed homeostasis using multiomic single-nucleus sequencing targeting RNA and accessible chromatin. Our study demonstrates that disrupted homeostasis in obese adipose tissue amplifies the systemic manifestations of psoriasis, highlighting the potential for developing interventions to control obesity-associated exacerbation of psoriasis.

Celecoxib and rofecoxib have different effects on small intestinal ischemia/reperfusion injury in rats.

Intestinal ischemia/reperfusion (I/R) injury is associated with high mortality and there is an unmet need for novel therapies. The intestinal expression of cyclooxygenase-2 (COX-2) increases rapidly after mesenteric I/R, but it is still a question of debate whether selective COX-2 inhibitors can mitigate I/R-induced gut injury. Here we aimed to compare the effect of celecoxib and rofecoxib, two selective COX-2 inhibitors, on intestinal I/R-induced injury in rats. Wistar rats were treated with celecoxib (10 and 100mg/kg), rofecoxib (5 and 50mg/kg), or vehicle for 8 days via gavage and then were subjected to sham operation or mesenteric I/R. Small intestinal inflammation and tissue damage were assessed by histology and quantification of inflammatory and tight junction proteins. The intestinal activity of COX enzymes was determined by a COX activity assay. The higher dose of celecoxib reduced the I/R-associated increase in inflammatory mediators (myeloperoxidase, pentraxin 3, COX-2, interleukin-1β) and loss of tight junction proteins (claudin-1, occludin), whereas the lower dose of celecoxib was only marginally effective. However, even high-dose celecoxib failed to prevent the histological injury of the mucosa. In contrast to celecoxib, rofecoxib did not affect intestinal inflammation and injury at any of the tested doses. Neither celecoxib nor rofecoxib affected the I/R-induced changes of HO-1 and PPAR-γ, known off-targets of COX-inhibitors, but celecoxib increased the I/R-induced elevation of Bax/Bcl-2, a marker of apoptosis, whereas rofecoxib reduced the elevation of phospho-Akt. Importantly, high-dose celecoxib, but not rofecoxib, has already reduced intestinal COX-1 activity. Our study provides evidence for the higher anti-inflammatory efficacy of celecoxib compared to rofecoxib in mesenteric I/R injury, which is likely due to its lower selectivity for COX-2. However, even high-dose celecoxib was unable to reduce the mucosal damage. Our results suggest that selective COX-2 inhibitors have only limited therapeutic value in intestinal I/R injury.

Starvation and Inflammation Modulate Adipose Mesenchymal Stromal Cells' Molecular Signature.

Mesenchymal stromal cells (MSCs) and their released factors (secretome) are intriguing options for regenerative medicine approaches based on the management of inflammation and tissue restoration, as in joint disorders like osteoarthritis (OA). Production strategy may modulate cells and secretome fingerprints, and for the latter, the effect of serum removal by starvation used in clinical-grade protocols has been underestimated. In this work, the effect of starvation on the molecular profile of interleukin 1 beta (IL1β)-primed adipose-derived MSCs (ASCs) was tested by assessing the expression level of 84 genes related to secreted factors and 84 genes involved in defining stemness potential. After validation at the protein level, the effect of starvation modulation in the secretomes was tested in a model of OA chondrocytes. IL1β priming in vitro led to an increase in inflammatory mediators' release and reduced anti-inflammatory potential on chondrocytes, features reversed by subsequent starvation. Therefore, when applying serum removal-based clinical-grade protocols for ASCs' secretome production, the effects of starvation must be carefully considered and investigated.

The relation between Parkinson's disease and non-steroidal anti-inflammatories; a systematic review and meta-analysis.

Background: Parkinson's disease (PD) is a neurological condition that typically shows up with aging. It is characterized by generalized slowness of movement, resting tremor or stiffness, and bradykinesia. PD patients' brains mostly exhibit an increase in inflammatory mediators and microglial response. Nevertheless, a variety of non-steroidal anti-inflammatory medications (NSAIDS) offered neuroprotection in animal models and preclinical trials. Aim: The current systematic review and meta-analysis were designed to try to resolve the debate over the association of NSAID use with the development of PD because the results of several studies were somehow contradictory. Methods: An intense search was performed on Scopus, PubMed, and Web of Science databases for articles relating the incidence of PD to the use of NSAIDs. Statistical analysis of the included studies was carried out using Review Manager version 5.4.1 by random effect model. The outcome was identified as the development of PD in patients who were on NSAIDs, ibuprofen only, aspirin only, and non-aspirin NSAIDs. This was analyzed using pooled analysis of odds ratio (OR) at a significance level of ≤0.05 and a confidence level of 95%. A statistically significant decreased risk of PD was observed in patients taking NSAIDs, Ibuprofen, and non-aspirin NSAIDs. Results: The ORs of PD occurrence in patients who took NSAIDs, Ibuprofen, and non-aspirin NSAIDs were 0.88 [95% CI (0.8-0.97), p = 0.01], 0.73 [95% CI (0.53-1), p = 0.05] and 0.85 [95% CI (0.75-0.97), p = 0.01]. Meanwhile, the risk of PD in patients who took aspirin was not statistically significant. Conclusion: In conclusion, Ibuprofen, non-aspirin NSAIDs, and other types of NSAIDs could be associated with a reduction in PD risk. However, there was no association between aspirin intake and the development of PD.

Microenvironmental interference with intra-articular stem cell regeneration influences the onset and progression of arthritis.

Studies have indicated that the preservation of joint health and the facilitation of damage recovery are predominantly contingent upon the joint's microenvironment, including cell-cell interactions, the extracellular matrix's composition, and the existence of local growth factors. Mesenchymal stem cells (MSCs), which possess the capacity to self-renew and specialize in many directions, respond to cues from the microenvironment, and aid in the regeneration of bone and cartilage, are crucial to this process. Changes in the microenvironment (such as an increase in inflammatory mediators or the breakdown of the extracellular matrix) in the pathological context of arthritis might interfere with stem cell activation and reduce their ability to regenerate. This paper investigates the potential role of joint microenvironmental variables in promoting or inhibiting the development of arthritis by influencing stem cells' ability to regenerate. The present status of research on stem cell activity in the joint microenvironment is also outlined, and potential directions for developing new treatments for arthritis that make use of these intervention techniques to boost stem cell regenerative potential through altering the intra-articular environment are also investigated. This review's objectives are to investigate these processes, offer fresh perspectives, and offer a solid scientific foundation for the creation of arthritic treatment plans in the future.

STRESS-INDUCED HYPERTHERMIA (LITERATURE REVIEW)

Stress-induced hyperthermia (SIH) is a physiological response of the body to psychological stress. Currently, 88 % of the population is in a state of chronic stress. Psychogenic hyperthermia is more common in young women. Psychogenic fever is not associated with an immunological inflammatory process, there is no increase in inflammatory mediators. The mechanism of the development of stress-induced hyperthermia is the activation of the sympathoadrenal system, vasoconstriction, an increase in the level of corticosterone and the thermogenesis of brown fat. Constant sympathetic stimulation leads to the formation of thermogenin-expressing loci in white adipose tissue. Dopaminergic and noradrenergic compounds do not affect the intensity of hyperthermia. Taking nonsteroidal analgesics does not affect this type of hyperthermia. Antipsychotics are ineffective for psychogenic hyperthermia. Effective drugs that have anxiolytic properties, which significantly reduce the basal body temperature when the dose is increased. Serotonergic receptors play a key role in modulating behavioural, autonomic, and endocrine responses to stress. Effective GABA agonists and antidepressants. For the treatment of the chronic variant of SIH, the use of fluoxetine is recommended. Psychoeducation is used as non-medicinal methods of treating functional fever; psychotherapy with an adjustment environment (verbal or non-verbal release of unreacted negative emotions and conflicts); cognitive-behavioral or other psychological therapy, meditation, relaxation training; yoga and practices aimed at reducing stress and mental disorders.

Nepetin Attenuates Atopic Dermatitis in HaCaT Cells and BALB/c Mice Through MyD88-MKK3/6-Akt Signaling.

Nepetin is a type of O-methylated flavone (6-hydroxy luteolin) and has been found in many herbal medicines that exhibit various pharmacological properties, including anti-inflammatory responses. Here, we aimed to investigate the efficacy of nepetin in attenuating inflammatory responses in cultured keratinocytes and 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD) in BALB/c mice. Various assay methods including cell viability, flow cytometry, fluorometry, confocal microscopy, western blot, ELISA techniques, staining methods, score and scratch frequency assessment, etc. were employed to explore the mechanisms. LPS-treated keratinocytes showed a significant increase in inflammatory mediators (iNOS, COX-2, PGES2, and NO) and cytokines (IL-1β, IL-6, and TNF-α) in a dose-dependent manner. Treatment with nepetin prevented LPS-induced cell death and inhibited inflammatory mediators and the production of cytokines in cultured keratinocytes. This inhibition was achieved by nepetin, which inhibited LPS-induced ROS production and the translocation of NF-κB in the cultures, thereby inhibiting the generation of inflammatory mediators and/or cytokines. In a mouse model of AD, treatment with nepetin reduced skin inflammation symptoms in a dose-dependent manner, as evidenced by the significant reduction of inflammation- related cytokines, skin lesions, and behavior scores. Based on the present in vitro and in vivo study, nepetin is the safest bioactive compound with potential therapeutic applications for AD-related skin lesions and adverse skin reactions.

Age-dependent inflammatory response is altered in an ex vivo model of bacterial pneumonia

BackgroundAging is associated with an increased incidence and mortality of Pseudomonas aeruginosa-induced pneumonias. This might be partly due to age-dependent increases in inflammatory mediators, referred to as inflamm-aging and a decline in immune functions, known as immunosenescence. Still, the impact of dysregulated immune responses on lung infection during aging is poorly understood. Here, we aimed to mimic inflamm-aging using ex vivo precision-cut lung slices (PCLS) and neutrophils – as important effector cells of innate immunity – from young and old mice and investigated the influence of aging on inflammation upon infection with P. aeruginosa bacteria.MethodsMurine PCLS were infected with the P. aeruginosa standard lab strain PAO1 and a clinical P. aeruginosa isolate D61. After infection, whole-transcriptome analysis of the tissue as well as cytokine expression in supernatants and tissue lysates were performed. Responses of isolated neutrophils towards the bacteria were investigated by quantifying neutrophil extracellular trap (NET) formation, cytokine secretion, and analyzing expression of surface activation markers using flow cytometry.ResultsInflamm-aging was observed by transcriptome analysis, showing an enrichment of biological processes related to inflammation, innate immune response, and chemotaxis in uninfected PCLS of old compared with young mice. Upon P. aeruginosa infection, the age-dependent pro-inflammatory response was even further promoted as shown by increased production of cytokines and chemokines such as IL-1β, IL-6, CXCL1, TNF-α, and IL-17A. In neutrophil cultures, aging did not influence NET formation or cytokine secretion during P. aeruginosa infection. However, expression of receptors associated with inflammatory responses such as complement, adhesion, phagocytosis, and degranulation was lower in neutrophils stimulated with bacteria from old mice as compared to young animals.ConclusionsBy using PCLS and neutrophils from young and old mice as immunocompetent ex vivo test systems, we could mimic dysregulated immune responses upon aging on levels of gene expression, cytokine production, and receptor expression. The results furthermore reflect the exacerbation of inflammation upon P. aeruginosa lung infection as a result of inflamm-aging in old age.

Cortisol level in mixed saliva as a marker of periodontal lesions in metabolic associated diseases

Dysregulation of cortisol levels at account of the increase in inflammatory mediators increases the risk of developing metabolic associated diseases, suppresses secretion of secretory immunoglobulins and neutrophil function, which results in a decrease in protection against periodontal pathogens in the oral cavity.
 Objective — to evaluate the possible association of salivary cortisol levels with the main inflammatory markers of metabolic associated diseases and periodontal disease.
 Materials and methods. The study included 67 patients, 44 of whom had cardiometabolic diseases. The comparison group consisted of patients, matched by sex and age who did not have clinical manifestations of metabolic associated diseases. To confirm the underlying disease, patients underwent assessment of carbohydrate and lipid metabolism, questionnaire survey on the main dental complaints and a dental examination, and evaluation of salivation rate, saliva viscosity and determination of cortisol level of mixed saliva with enzyme linked immunosorbent assay. Statistical analysis was performed using SPSS software with the calculation of the mean value M, standard error, Student’s test. Percentages were compared using the z‑criterion. The Pearson correlation test was used to identify the relationship between indicators.
 Results. Significantly higher levels of mixed salivary cortisol were recorded in patients of the main group (3.34±0.20 ng/ml) (p <0.05). Direct correlation has been established between cortisol levels and presence of diabetes mellitus (r=0.342; p=0.016), levels of blood glucose (r=0.379; p=0.002), low‑density lipoprotein cholesterol (r=0.348; p=0.017); indirect correlation was established with non‑alcoholic fatty liver disease (NAFLD) through triglycerides levels (r=0.345; p=0.007). In addition, reverse correlations were observed between cortisol and alkaline phosphatase (r=–0.328; p=0.0014), salivation rate and the presence of metabolic associated diseases (the most significant with NAFLD (r=–0.499; p=0.000)).
 Conclusions. Under conditions of prolonged chronic stress, patients with metabolic associated diseases have a significantly increased rate of gingival lesions. The study of cortisol in mixed saliva is a convenient non‑invasive method that allows the assessment of the presence of chronic stress in patients, as well as its impact on the development, duration, chronicity and response to treatment of metabolic associated diseases.

Patulin Ameliorates Hypertrophied Lipid Accumulation and Lipopolysaccharide-Induced Inflammatory Response by Modulating Mitochondrial Respiration.

Patulin (PAT) is a natural mycotoxin found in decaying pome fruits. Although some toxicological studies have been conducted on PAT, recent research has highlighted its anticancer and antifungal effects. However, studies have yet to examine the effects and molecular mechanisms of PAT in other metabolic diseases. Obesity is a chronic disease caused by excessive food intake and abnormal lifestyle, leading to low-grade inflammation. Therefore, this study aimed to elucidate the effect of PAT on obesity at the cellular level. PAT treatment reduced lipid accumulation, suppressed glucose and LDL uptake, inhibited lipid deposition and triglyceride synthesis, upregulated fatty acid oxidation-related genes (Pgc1α), and downregulated adipogenic/lipogenic genes (Pparγ and C/ebpα) in hypertrophied 3T3-L1 adipocytes. Additionally, PAT treatment enhanced mitochondrial respiration and mass in differentiated adipocytes and alleviated inflammatory response in activated RAW 264.7 macrophages. Moreover, PAT treatment downregulated pro-inflammatory genes (il-6, Tnf-α, Cox-2, and inos), suppressed lipopolysaccharide (LPS)-induced increase in inflammatory mediators (IL-6, TNF-α, and NO), and restored mitochondrial oxidative function in LPS-stimulated macrophages by improving oxygen consumption and mitochondrial integrity and suppressing ROS generation. Overall, these findings suggest a potential for PAT in the prevention of lipid accumulation and inflammation-related disorders.

Immune responses of patients on maintenance hemodialysis after infection by SARS-CoV-2: a prospective observational cohort study

BackgroundImmune dysregulation in patients with acute COVID-19 under chronic hemodialysis (CHD) is fully not elucidated. The changes of mononuclear counts and mediators before and after HD and associations with final outcome were studied.MethodIn this prospective study, hospitalized patients with moderate-to-severe COVID-19 under CHD and matched comparators under HD were analyzed for their absolute counts of lymphoid cells and circulating inflammatory mediators. Blood samples were collected before start and at the end of the first HD session; dialysate samples were also collected.ResultFifty-nine patients with acute COVID-19 under CHD and 20 uninfected comparators under CHD were enrolled. Circulating concentrations of tumor necrosis factor-alpha (TNFα), interleukin (IL)-10, interferon-γ and platelet-derived growth factor-A were increased in patients. Concentrations of mediators did not differ before and after HD. Significant decreases of CD4-lymphocytes and CD19-lymphocytes were found in patients. The decrease of the expression of HLA-DR on CD14-monocytes was associated with unfavorable outcome (defined as WHO-CPS 6 or more by day 28); increased counts of CD19-lymphocytes were associated with better outcomes.ConclusionPatients under CHD develop an inflammatory reaction to SARS-CoV-2 characterized by increase of inflammatory mediators, decrease of circulating T-lymphocytes and decrease of the expression of HLA-DR on CD14-monocytes.

Higher serum lipocalin 2 is associated with post-stroke depression at discharge

Background and aimsPost-stroke depression (PSD), as one of the common complications after stroke, seriously affects the physical and mental health and functional prognosis of patients. Previous studies have shown that the increase of inflammatory mediators is associated with the occurrence of PSD. Lipocalin 2 (LCN2), as an acute phase protein, is involved in the development of acute ischemic stroke (AIS), and its expression is up-regulated in patients with depression, suggesting that there is a potential correlation between serum LCN2 and depression. The aim of this study was to explore the relationship between serum LCN2 at admission and PSD at discharge.MethodsA total of 358 AIS patients were retrospectively included. All patients had fasting venous blood taken within 24 h of admission to detect serum LCN2. The patients were evaluated by 17-item Hamilton Depression Scale (HAMD) before discharge. Patients with HAMD score > 7 were diagnosed with PSD. The correlation between serum LCN2 and PSD was tested using binary logistic regression analysis.ResultsIn our study, 92 (25.7%) patients were diagnosed with PSD at discharge. According to the serum LCN2 value, the patients were divided into three layers (Tertile1 ≤ 105.24ng/ml; Tertile2: 105.24-140.12ng/ml; Tertile3 ≥ 140.12ng/ml), with T1 layer (the lowest levels) as a reference, after adjusting for multiple potential confounding factors, T3 layer (the highest levels) was independently associated with the occurrence of PSD (odds ratio [OR] = 2.639, 95% confidence interval [CI]: 1.317–5.287, P = 0.006). Similar results were found when the serum LCN2 was analyzed as a continuous variable. The optimal cut-off value of serum LCN2 at admission to predict PSD at discharge was 117.60ng/ml, at this threshold, the sensitivity was 77.2%, and the specificity was 53.4%.ConclusionsHigh serum LCN2 levels at admission are an independent risk factor for PSD in patients with AIS at discharge.

The Effectiveness of Using Herbal Packages (VCO, Honey, Black Seed) as Alternative Treatment for Covid-19 in the Community

<div><table cellspacing="0" cellpadding="0" align="left"><tbody><tr><td align="left" valign="top"><p><em>Covid-19 is an infectious disease that can cause death. Herbal medicines have anti-inflammatory properties associated with cytokine storm development. This means it prevents increases in inflammatory mediators, erythrocyte sedimentation rate (ESR), interleukin (IL)-6, and C-reactive protein (CRP). This study aimed to determine the effectiveness of using herbal packages (VCO, honey, Black Seed) as an alternative treatment for Covid-19 in the community. This research is a Quasi-experimental quantitative study with a control group design (control group design) Pretest-Posttest Control Group Design design. This research was conducted in Boyolali Regency. This research was conducted from October 2022 - January 2023. The population in this study were individuals with a history of Covid-19 disease in Boyolali Regency, 82 in December 2022. The research sampling technique was simple random sampling. The research sample consisted of 46 people consisting of the intervention group of 23 respondents and the control group of 23 respondents. The research instruments were questionnaires, observation forms, and other forms, and measurements were made using a sphygmomanometer, oxymeter, and thermometer. Analysis of bivariate analysis research data using the Paired Sample t-test, Independent Sample t-test, and the help of the SPSS software computer application. The analysis results obtained the p-value for saturation measurement in the treatment group, namely p = 0.024 <0.05, and for temperature measurements, p = 0.014 <0.05, so it can be concluded that herbal packages are effective as an alternative treatment for the Covid-19 virus in the community. It is known that most respondents in the treatment group felt better after consuming the herbal package. Herbal packages have proven effective in dealing with the sequelae caused by Covid-19 and are effective as a companion to the treatment of Covid-19 patients.<strong></strong></em></p><p><strong><em> </em></strong></p></td></tr></tbody></table></div><strong><em>Keywords:</em></strong><em> <strong> Black Seed, Covid-19, Effectiveness, Honey, Virgin Coconut Oil</strong></em>

Prognostic impact of the controlling nutritional status score in Chinese patients undergoing cardiac surgery

Prognostic impact of the controlling nutritional status score in Chinese patients undergoing cardiac surgery

Hemoadsorption in Heart Failure Requiring Mechanical Circulatory Support-A Systematic Review and Meta-Analysis.

Left ventricular assist devices (LVAD) and extracorporeal membrane oxygenation (ECMO) are well established therapies in heart failure (HF) management. Their use is generally associated with a sudden increase in inflammatory mediators, which are often already elevated in patients with HF prior to device implantation. An exaggerated release of proinflammatory cytokines is associated with organ dysfunction and increased mortality. Hemoadsorption has been shown to reduce inflammatory mediators during cardiopulmonary bypass. To investigate the role of hemoadsorption during the management of acute or chronic heart failure with mechanical circulatory support and its impact on survival. We systematically searched MEDLINE selecting all studies comparing the use of hemoadsorption during LVAD implantation or veno-arterial (v.a.) ECMO therapy. Records were screened by two different investigators. Reports without a control group and duplicates were excluded. Our search delivered six studies. One was randomized and five were retrospective studies, of which three were risk-adjusted. During LVAD implantation, one study showed no difference in mortality but higher incidence of respiratory insufficiency in the hemoadsorption group (54% vs 30%, p = 0.024) and the other study found higher mortality in the hemoadsorption group (33% vs 0%, p = 0.01). During ECMO therapy, three of four studies including the randomized one found no difference in survival or major adverse cardiac events between the hemoadsorption and the control groups. Only one study found lower mortality in the hemoadsorption group (20% vs 60%. p = 0.02). The results of this literature review suggest that the use of hemoadsorption in patients undergoing LVAD implantation might be associated with higher morbidity and mortality. The majority of studies on the use of hemoadsorption during v.a. ECMO therapy showed no effect on mortality or organ dysfunction, while only one small study showed that hemoadsorption was able to reduce mortality. The results are limited by the retrospective nature and the small sample sizes of the majority of the studies included.

Smoking induces increased apoptosis in osteoblasts: changes in bone matrix organic components

Clinical studies demonstrate the impact of smoking on bone tissue fragility and higher incidence of fractures. However, it is not totally understood which physiological mechanisms could be involved in these events. Previously, we showed important changes in bone tissue components in experimental model of cigarette smoke (CS) exposure. CS exposure induces worsening in bone mineralization and a decrease in collagen type I deposition, leading to bone fragility. Considering that the majority of clinical studies described bone structural changes by radiographic images, in this study we performed analyses “in situ” using tissue samples from smokers, former smokers and non-smokers to better understand how the increase in inflammatory mediators induced by smoking exposure could interfere in bone cells activity leading bone structural changes. We observed increased levels of IL-1β, IL-6 and TNF-α in bone tissue homogenates with a concomitant increase in osteoblast apoptosis in smokers and former smokers compared with non-smokers. Histological changes in both smokers and former smokers were characterized by reduction in collagen type I. Only in smokers, it was observed decrease in trabecular area, suggesting increased bone resorption and increase in collagen type V. These results showed that osteoblasts apoptosis in association with increased bone resorption leads bone structural changes in smokers.

Effects of different anesthesia methods on postoperative immune function in patients undergoing gastrointestinal tumor resection

To investigate the effects of different anesthetic methods on postoperative immune function in patients undergoing gastrointestinal tumor resection. Ninety patients undergoing laparoscopic gastrointestinal tumor resection were divided into 3 groups. Patients in the GA group were anesthetized by total intravenous anesthesia. The GE group was anesthetized by general anesthesia combined with epidural anesthesia. The GN group was anesthetized by general anesthesia combined with bilateral Transversus Abdominis Plane block (TAP) and rectus sheath nerve blocks. General anesthesia is total intravenous anesthesia in all three groups. Blood samples were taken to test the changes of peripheral lymphocyte subtype analysis, and levels of plasma cortisol, epinephrine, norepinephrine. Also, the dosage of anesthetic drugs, recovery time, and visual analog scale (VAS) scores were recorded. Postoperative immune indexes, including CD4 count, CD8 count, B, and NK cells, in the GE group were significantly higher than those in NA and GA groups (P < 0.01). Perioperative stress indices, including epinephrine levels, norepinephrine level and aldosterone level, in the GE group were significantly lower than in the GA group and GN group (P < 0.01). The intraoperative/total sufentanil dosage and remifentanil dosage in the GE group were significantly lower than those in the GA and GN groups (P < 0.01). The VAS scores in the GE group were significantly better than those in GA and GN groups (P < 0.01). General anesthesia combined with epidural anesthesia attenuates the increase in inflammatory mediators. Its possible mechanisms include reducing perioperative stress response and reducing perioperative opioid use.

Impact of Chronic Rhinosinusitis with Nasal Polyposis on IL-12 and IL-8.

The pathophysiology of Chronic Rhinosinusitis is coordinated by distinct inflammatory reactions in different individuals. Inflammatory environments with a predominance of Th2 lymphocytes tend also to be rich in eosinophils. These environments are common during the formation of nasal polyps associated with aspirin intolerance, which is also marked by an increase in inflammatory mediators, especially IL-4, IL-5, and IL-13. Despite the significance of these inflammatory mediators, the relevance of IL-12 subunits' presence within eosinophilic nasal polyps, however, has been less studied. The current study aims to evaluate the presence of IL-12 subunits, IL-12p40 and IL-12p70, in eosinophilic nasal polyps and their correlations with IL-8 presence. We compared the concentrations of IL-8, IL12p40, and IL12p70 among samples of eosinophilic nasal polypoid tissue, eosinophilic nasal polypoid tissue associated with aspirin intolerance, and healthy nasal mucosa, using an indirect immunoassay (ELISA) kit. When compared to healthy nasal mucosa, there was a lower concentration of IL-8 in Chronic Rhinosinusitis with Nasal Polyp (CRSwNP) tissue. Aspirin Intolerant polypoid tissue also presented a lower concentration of IL-12 subunits compared to healthy nasal mucosa. There was no significant correlation between IL-8 and IL-12 in the eosinophilic polypoid conditions. In CRSwNP, there is a reduction in IL-8 and IL-12 subunits compared to control, with a lack of correlation between IL-12 and IL-8. The lack of correlation can be justified by a type two inflammatory storm environment.

Systemic Inflammatory Response as a Prognostic Factor in Breast Cancer. Part I. Tumor-Promoting Inflammation. Serum Inflammatory Markers

Chronic inflammation caused by exposure to external or internal factors increases the risk of developing malignancies and promotes tumor progression due to the influence on the key elements of carcinogenic mechanisms. At the system level signs of a chronic inflammation are manifested by an increase of inflammatory mediators and acute phase proteins levels in the blood, a change in the ratio of circulating leukocyte populations, and disturbances in the hemostasis system. This review is devoted to serum and hematological parameters of the systemic inflammatory response (SIR) in breast cancer (BC). The first part of the review outlines general concept about the role of inflammatory factors in the development of malignant tumors. It provides information on the most well studied serum inflammatory markers in breast cancer: cytokines, including interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-), as well as C-reactive protein (CRP). The main properties of these polypeptides, which link them with tumor-promoting inflammation, are considered. An analysis of the data on the clinical significance of the serum level of cytokines and CRP in breast cancer accumulated to date is presented. Correlations of the elevated levels of the serum inflammatory markers with clinical and morphological characteristics of the disease, tumor response to chemotherapy, overall and relapse-free survival of patients indicate the feasibility of in-depth investigation of the issue for the purpose of the practical application of the systemic inflammatory markers as predictive and prognostic indicators in BC.

Biologically Synthesized Rosa rugosa-Based Gold Nanoparticles Suppress Skin Inflammatory Responses via MAPK and NF-κB Signaling Pathway in TNF-α/IFN-γ-Induced HaCaT Keratinocytes.

Nanotechnology-applied materials and related therapeutics have gained attention for treating inflammatory skin diseases. The beach rose (Rosa rugosa), belonging to the family Rosaceae, is a perennial, deciduous woody shrub endemic to northeastern Asia. In this study, R. rugosa-based gold nanoparticles (RR-AuNPs) were biologically synthesized under optimal conditions to explore their potential as anti-inflammatory agents for treating skin inflammation. The synthesized RR-AuNPs were analyzed using field emission-transmission electron microscopy, energy-dispersive X-ray spectrometry, selected-area electron diffraction, and X-ray diffraction. The uniformly well-structured AuNPs showed near-spherical and polygonal shapes. Cell viability evaluation and optical observation results showed that the RR-AuNPs were absorbed by human keratinocytes without causing cytotoxic effects. The effects of RR-AuNPs on the skin inflammatory response were investigated in human keratinocytes treated with tumor necrosis factor-α/interferon-γ (T + I). The results showed that T + I-stimulated increases in inflammatory mediators, including chemokines, interleukins, and reactive oxygen species, were significantly suppressed by RR-AuNP treatment in a concentration-dependent manner. The western blotting results indicated that the RR-AuNP-mediated anti-inflammatory effects were highly associated with the suppression of inflammatory signaling, mitogen-activated protein kinase, and nuclear factor-κB. These results demonstrate that plant extract-based AuNPs are novel anti-inflammatory candidates for topical application to treat skin inflammation.