Expert consensus on the integrated diagnosis of idiopathic multicentric Castleman disease / Consenso de expertos sobre el diagnóstico integrado de la enfermedad de Castleman idiopática multicéntrica

Idiopathic multicentric Castleman disease (iMCD) is rare. The differential diagnosis includes inflammatory, autoimmune and neoplastic disease. The identification of the histopathological features of Castleman disease in the lymph node is the main diagnostic criterion.Fifty-three experts from three medical societies (SEMI, SEHH and SEAP) have created a multi-disciplinary consensus document in order to standardise the diagnosis of Castleman disease. Using the Delphi method, specific recommendations for the initial clinical, laboratory and imaging studies have been made for an integrated diagnosis of iMCD as well as for the best way to obtain samples for histopathological confirmation, correct laboratory procedure and interpretation and reporting of results.(AU)

La enfermedad de Castleman multicéntrica idiopática (ECMi) es una patología infrecuente. El diagnóstico diferencial incluye patología inflamatoria, autoinmune y neoplásica. El estudio anatomopatológico del ganglio linfático y la identificación de las características histopatológicas de la enfermedad de Castleman constituyen un criterio principal para el diagnóstico.Con el objetivo de estandarizar el proceso diagnóstico de esta patología, se ha desarrollado un documento de consenso multidisciplinario con la participación de 53 expertos de tres sociedades médicas (Sociedad Española de Medicina Interna [SEMI], Sociedad Española de Hematología y Hemoterapia [SEHH] y Sociedad Española de Anatomía Patológica [SEAP]). Mediante el método Delphi se han validado las recomendaciones específicas para el diagnóstico integrado de la ECMi con respecto a los estudios clínicos, de laboratorio y de imagen necesarios en el abordaje inicial del paciente y las recomendaciones acerca de la mejor obtención de muestras para confirmación histopatológica, así como procedimientos de laboratorio para el estudio de las muestras, interpretación de resultados y emisión de un informe anatomopatológico.(AU)

Salivary biomarkers present in patients with periodontitis without clinical distinction: findings from a meta-analysis

Background: A new classification for periodontitis has been adopted in clinical practice. However, there are still discussions regarding this new classification and difficulties in its adoption, both by professionals and researchers. Thus, this study aimed to evaluate which salivary biomarkers are present in periodontitis, following the new classification of periodontal diseases through meta-analysis. Material and methods: A literature search was carried out in the scientific databases: PubMed, Scielo and Google scholar to select studies. The selection of studies was followed by two authors upon reading of the title, abstract and full text. The necessary data were collected and statistical analyses were performed using the Review Manager statistical software version 5.4, with calculation of Mean Difference, heterogeneity (I²) and funnel plot with P < 0.05. Results: After following the selection criteria, 9 articles were selected for comparison. The studies address the presence of biomarkers in the saliva of patients with periodontitis and their possible use in the monitoring and diagnosis of the disease. For the meta-analytic comparison, a sample size of 1,983 individuals was used. Statistical analyses showed that nitric oxide, IL-6, IL-1B and osteoprotegerin are substances that are significantly present in patients with periodontitis (P < 0.05). Conclusions: IL-6, nitric oxide, IL-1B, TNF-α and osteoprotegerin are among the most present biomarkers in patients with periodontitis, and may be used in the future as a monitoring of periodontal disease. The present study also revealed that there was no statistically significant difference in the concentration of these biomarkers for clinical distinction from periodontitis. (AU)

Role of selected salivary inflammatory cytokines in the diagnosis and prognosis of oral squamous cell carcinoma. A Systematic Review and Meta-analysis

Background: Oral squamous cell carcinoma (OSCC) is gradually increasing its incidence in our society. Unfortunately, this entity is diagnosed at an advanced stage in most patients, a fact that implies greater difficulty in its treatment and a worse prognosis. This systematic review aims to assess whether the cytokines IL-6, IL-8 and TNF-α are potential salivary biomarkers that allow early diagnosis of cancer. Material and methods: An electronic search was performed in three databases (Pubmed, Scopus and Web of Science). We used the following keywords: "salivary cytokines", "saliva cytokines", "salivary interleukins", "biomarkers", "oral squamous cell carcinoma" and "diagnosis", combined with the Boolean operators "AND" and "OR". Results: 128 publications were found and finally 23 articles were included in the review and 15 in the meta-analysis. It has been observed that the majority of OSCC patients express higher salivary concentrations of IL-6, IL-8 and TNF-α compared to the control (CL) and premalignant lesion (OPML) groups. It has also been observed that the different premalignant lesions do not have statistically significant differences in the salivary concentration of the cytokines, and on the other hand, differences have been observed between the different TNM stages. The meta-analysis has shown that the difference in concentration of IL-6, IL-8 and TNF-α is statistically significant between the CL group and the OSCC, and also between the CL group and OPML. Conclusions: There is sufficient evidence to affirm that IL-6, IL-8 and TNF-α are useful salivary cytokines in the early diagnosis and prognosis of OSCC. Although future studies are necessary to establish greater reliability of these biomarkers and thus be able to develop a valid diagnostic test. (AU)

Effect of Individualized PEEP on Perioperative Pulmonary Complications in Elderly Patients with Prostate Cancer Undergoing General Anesthesia in Trendelenburg Position: A Single-Center Retrospective Study

Objective: This study aimed to explore the effect of individualized positive end-expiratory pressure (PEEP) on postoperative pulmonary complications (PPCs) in elderly patients with prostate cancer undergoing general anesthesia in Trendelenburg position (low-head and high-foot position at about 45° when patients were in supine position). Methods: The clinical data of 96 elderly patients undergoing Leonardo’s robotic-assisted laparoscopic radical prostatectomy in Zhejiang Provincial People’s Hospital from October 2021, to April 2023, were selected for retrospective analysis. Sixteen patients who had interrupted follow-up or did not meet the inclusion criteria were excluded, and 80 patients were finally included. The patients were divided into group A (lung-protective strategy using routine PEEP value, n = 40) and group B (lung-protective strategy using individualized PEEP value, n = 40) on the basis of different inversion methods. The PEEP value of group A was set as 5 cmH2O, whereas that of group B was determined under the guidance of static lung compliance. The incidences of PPCs on postoperative day 7 were statistically analyzed, and the serum levels of interleukin (IL) 6 (IL-6) and IL-8 in both groups were measured by enzyme-linked immunoadsordent assay (ELISA). Results: The incidence of pulmonary complications was obviously lower in group B than in group A on postoperative day 7 (p < 0.001). Group B had lower levels of serum IL-6 and IL-8 at the end of surgery (T1) and 12 h after surgery (T2, p < 0.001); Higher oxygenation index values 10 min after successful titration of individualized PEEP (A3), 1 h after individualized PEEP ventilation (A4), 2 h after individualized PEEP ventilation (A5), 10 min after recovery of supine position (A6), and 30 min after tracheal extubation (A7); And lower hospitalization time (all p < 0.001) than group A (AU)

Si-Ni-San Ameliorates the Clinical Symptoms of Interstitial Cystitis/Bladder Pain Syndrome in Rats by Decreasing the Expression of Inflammatory Factors

Objective: To observe the therapeutic effect of Si-Ni-San (SNS) on interstitial cystitis/bladder pain syndrome (IC/BPS) in rats, and explore the possible regulatory mechanism of SNS on IC/BPS combined with transcriptome analysis. Methods: An IC/BPS model of Sprague–Dawley (SD) rats was established with cyclophosphamide (CYP), and the SNS was extracted for treatment. The rats were divided into 4 groups (n = 10 in each group): Control group (blank), cyclophosphamide group (CYP group, CYP injection + normal saline gavage), lower-dose SNS group (LSNS group, CYP injection + 6 g/kg SNS gavage), and higher-dose SNS group (HSNS group, CYP injection + 12 g/kg SNS gavage). Urination, pain, and histological changes were observed in the rats after the experiment, and Western blotting (WB) and transcriptome analysis were performed on bladder tissues. Results: Compared with the CYP group, the urination, pain and inflammation symptoms of the IC/BPS model rats in the SNS treatment groups (LSNS and HSNS) were significantly improved (p < 0.05). WB results showed that the expressions of inflammation-related proteins interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the SNS treatment groups were significantly decreased compared with those in the CYP group. Transcriptome results showed that SNS can affect the expression of inflammation-related genes and inflammatory signaling pathways. Conclusions: SNS can significantly alleviate the symptoms of inflammation and pain in IC/BPS rats, and its mechanism may be related to the down-regulation of inflammatory factors IL-6 and TNF-α through messenger RNA (mRNA) and long non-coding RNA (LncRNA) pathways (AU)

Predictive value of C-reactive protein, procalcitonin, and interleukin-6 on 30-day mortality in patients with bloodstream infections / Valor predictivo de la proteína C reactiva, procalcitonina e interleucina-6 en la mortalidad a los 30 días en pacientes con infecciones del torrente sanguíneo

Background We aimed to assess the predictive performance of C-reactive protein (hsCRP), procalcitonin (PCT), and interleukin-6 (IL-6) at different times points of bloodstream infections (BSI) management. Methods The cases were collected from January 2020 to June 2021 in the First Affiliated Hospital of Xinjiang Medical University (n=185). We collected patients’ records of hsCRP, PCT, and IL-6 serum levels and calculated the clearance of these biomarkers on day 1, day 3, and day 5 (hsCRP-1, hsCRP-3, hsCRP-5, so do PCT, and IL-6). We analyzed these predictive performances for 30-day mortality with ROC and Logistic regression. The correlation between biomarkers and their clearance rates was performed by a rank correlation method. Results The 30-day mortality was 11.35% (21/185). Serial serum hsCRP-3, IL-6-3, PCT-1, PCT-3, and PCT-5 were statistically higher in BSI mortality than survivors. Significant predictive ability was found for 30-day mortality with blood culture (BC) reported fungi (OR, 0.033; 95% CI: 0.002–0.535) and PCT-5 (OR, 1.045; 95% CI: 1.013–1.078) levels, respectively. The AUC of PCT-5 levels for 30-day mortality was 0.784 (95% CI 0.678–0.949), and the cut-off value was 5.455ng/mL. Conclusions PCT-5 is more valuable for the prognosis of 30-day mortality in patients with BSI compared to the other inflammatory biomarkers (AU)

Antecedentes Nuestro objetivo fue evaluar el rendimiento predictivo de la proteína C reactiva (hsCRP), procalcitonina (PCT) e interleucina-6 (IL-6) en distintos momentos del tratamiento de pacientes con infecciones del torrente sanguíneo. Métodos Los casos se recogieron entre enero de 2020 y junio de 2021 en el Primer Hospital Afiliado de la Universidad Médica de Xinjiang (n = 185). Los valores de los niveles séricos de hsCRP, PCT e IL-6 se obtuvieron de los registros de los pacientes y calculamos la depuración de estos biomarcadores en el día 1, el día 3 y el día 5 (hsCRP-1, hsCRP-3, hsCRP-5, PCT e IL-6). Analizamos estos rendimientos predictivos para la mortalidad a 30 días con ROC y regresión logística. La correlación entre los biomarcadores y sus tasas de eliminación se realizó mediante un método de correlación de rangos. Resultados La mortalidad a 30 días fue de 11,35% (21/185). Los valores séricos seriados de hsCRP-3, IL-6-3, PCT-1, PCT-3 y PCT-5 fueron estadísticamente más elevados en los pacientes fallecidos de infecciones del torrente sanguíneo que en los supervivientes. Se halló una capacidad predictiva significativa para la mortalidad por hongos (OR, 0,033; IC 95%: 0,002-0,535) y el valor de PCT-5 (OR, 1.045; IC 95%: 1.013-1.078), respectivamente. El AUC de los niveles de PCT-5 para la mortalidad a 30 días fue de 0,784 (IC 95%: 0,678-0,949), y el valor de corte fue de 5.455 ng/mL. Conclusiones La PCT-5 fue un parámetro de más valor para el pronóstico de mortalidad a 30 días en pacientes con infecciones del torrente sanguíneo en comparación con los demás biomarcadores inflamatorios (AU)

Association between interleukin-6 and lower urinary tract symptoms of benign prostatic hyperplasia / Relación entre la interleucina-6 y los síntomas urinarios de la hiperplasia prostática benigna

Objective: To evaluate the association between IL-6 in prostatic tissue/blood sample and BPH-LUTS, so as to preliminarily discover an indicator of inflammation that could show the severity of LUTS. Patients and methods: The prostatic tissues and blood samples were collected from 56 patients who underwent transurethral plasmakinetic resection of the prostate (TUPKRP). The association between IL-6 detected on prostatic tissues/blood sample and LUTS parameters, including international prostate symptom score (IPSS), peak flow rate (Qmax) and urodynamic parameters were analyzed with SPSS version 18.0, and p-value <0.05 was chosen as the criterion for statistical significance. Results: The TPSA and prostate volume (PV) were found to be higher in the inflammation group (p=0.021, 0.036). There was a positive association between prostate tissue inflammation and LUTS ([IPSS, storage symptoms score (SSS), voiding symptoms score (VSS), p<0.05], [Qmax, p=0.025], [obstruction, p=0.027] and [AUR, p=0.018]). The level of serum IL-6 was significantly higher in inflammatory group (p=0.008). However, no differences were observed in different degrees of inflammation (p=0.393). The level of IL-6 in prostatic tissue significantly increased with the degree of inflammation (p<0.001), and the intensity of IL-6 expression was statistically correlative with the degree of inflammation (p<0.001). The IL-6 expression in prostatic tissue was statistically relevant with IPSS (p=0.018) and SSS (p=0.012). Conclusion: IL-6 expression in prostatic tissue is associated with storage IPSS, suggesting chronic inflammation might contribute to storage LUTS. (AU)

Objetivo: Evaluar la relación entre il-6 y bph-lut en muestras de tejido prostático/sangre, con el fin de identificar indicadores de inflamación que reflejen la gravedad de los lut. Pacientes y métodos: Se recolectaron muestras de tejido prostático y sangre de 56 pacientes sometidos a una plasmatectomía transuretral prostática. Se aplicó la versión 18.0 de SPSS para analizar la correlación entre el il-6 de tejido prostático/muestra de sangre y los parámetros relacionados con los LUTS (puntuación internacional de síntomas prostáticos (IPSS), flujo máximo (Qmax), parámetros urodinámicos), con UN valor p<0,05 como criterio para una diferencia estadísticamente significativa. Resultados: Hubo diferencias estadísticamente significativas (p=0,021, 0,036) entre el grupo con inflamación y el grupo sin inflamación en TPSA y PV. La inflamación del tejido prostático se relacionó positivamente con LUTS ([IPSS, puntuación de síntomas de almacenamiento (SSS), puntuación de síntomas de micción (VSS), p<0,001), y la intensidad de la expresión de il-6 se correlacionó estadísticamente con el grado de inflamación (p<0,001). La expresión de il-6 en el tejido prostático fue estadísticamente significativa con IPSS (p=0,018) y SSS (p=0,012). Conclusiones: La expresión de il-6 en el tejido prostático está relacionada con el almacenamiento de IPSS, lo que sugiere que la inflamación crónica puede estar involucrada en el almacenamiento de LUTS. (AU)

P2X and P2Y Receptor Antagonists Reduce Inflammation in ATPinduced Microglia

Background: P2 receptors have been implicated in the release of neurotransmitter and pro-inflammatory cytokines due to their response to neuroexcitatory substances in the microglia. The P2X4, P2X7 and P2Y12 receptors are involved in the development of pain behavior induced by peripheral nerve injury. However, it is not known if blocking P2X4, P2X7 and P2Y12 receptors is associated with the expression and the release of interleukin-1B (IL-1β), interleukin-6 (IL-6), or tumor necrosis factor-α (TNF-α) in cultured neonatal spinal cord microglia. Objective: For this reason, we examined the effects of P2X4, P2X7 and P2Y12 antagonists on the expression and the release of IL-1β, IL-6, and TNF-α in ATP-stimulated microglia. Methods: In this study, we observed the effect of A-740003, PSB-12062 and MRS 2395 (P2X4, P2X7 and P2Y12 receptors antagonist, respectively), on the expression and release of IL-1β, IL-6 and TNF-α by using real-time fluorescence quantitative polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). Results: ATP induced the increased expression of IL-1β, IL-6 and TNF-α at the level of messenger RNA (mRNA). ATP-evoked increase in IL-1β, IL-6 and TNF-α mRNA expression was inhibited by the P2X4 receptor antagonist A-740003 or P2X7 receptor antagonist PSB-12062, respectively. Similarly, ATP-evoked release of IL-1β, IL-6 and TNF-α was inhibited by A-740003 and PSB-12062. Furthermore, ATP-evoked increased expression of Iba-1, IL-1β, IL-6 and TNF-α mRNA, and release of IL-1β, IL-6 and TNF-α were nearly all blocked after co-administration of A-740003 plus PSB-12062. Finally, ATP-evoked increased gene expression and release of IL-1β, IL-6 and TNF-α were also inhibited by MRS 2395 (P2Y12 antagonist). Conclusion: These observations suggest a new clue for therapeutic strategies to treat the neuro-inflammation. (AU)

IL-6 secretion of CD4+ T cells stimulated by LC3-positive extracellular vesicles in human epithelial ovarian cancer

Ovarian cancer (OC) as the most fatal gynecological malignancy worldwide, with epithelial ovarian cancer (EOC) being the predominant and most lethal form, poses a serious threat to human health. LC3-positive extracellular vesicles (LC3+ EVs) promote tumorigenesis by educating CD4+ T cells in a murine melanoma model. However, regulation of LC3+ EVs in human EOC remains largely unknown. MethodsDifferential analysis of Rab8a, Hsp90α and Il6 expression was performed using GEPIA2. The number of LC3+ EVs and the frequency of Heat shock protein 90α+ LC3+ EVs (HSP90α+ LC3+ EVs) in the ascites of EOC patients were tested by flow cytometry. IL-6, IL-10, IFN-γ, IL-4 and TGF-β were measured by ELISA. CD4+ T cells were isolated from peripheral blood of healthy human donors using MACS magnetic bead technology. ResultsHigher Rab8a, Hsp90a and Il6 expression of cancer tissues compared with normal adjacent tissues in OC were found. The level of IL-6 was positively correlated with LC3+ EVs number, HSP90α+ LC3+ EVs percentage in the ascites, and ROMA index of the patient. In addition, elevated IL-6 production by CD4+ T cells induced by LC3+ EVs was observed, which was suppressed by anti-HSP90α or anti-TLR2. ConclusionsLC3+ EVs level and HSP90α+ LC3+ EVs percentage were associated with elevated IL-6 in the ascites of EOC patients. HSP90α on LC3+ EVs from human EOC could stimulate CD4+ T cell production of IL-6 via TLR2. (AU)

Waist-to-height ratio cut-off points to predict obesity in adolescents and association with inflammatory markers / Puntos de corte de la relación cintura-altura para predecir la obesidad en adolescentes y asociación con marcadores inflamatorios

Introduction: obesity increases inflammatory molecules and cardiovascular risk even in young populations. New indicators are being investigated, including the waist-to-height ratio (WHtR) to predict obesity and the relationship with inflammatory markers in childhood and adolescence. Objective: to identify the cut-off points of the WHtR to determine obesity and its association with inflammatory markers in adolescents in São Luís, state of Maranhão, Brazil. Methods: this is a cross-sectional study, with 2,209 adolescents aged 18 and 19, belonging to the third phase of the birth cohort entitled “RPS”, carried out in 2016. The total area under the ROC curve (AuC) was identified to assess the predictive capacity of WHtR in relation to body fat percentage (%BF), obtained by air displacement plethysmography (ADP). The association of WHtR with inflammatory markers interleukin-6 (IL-6), tumor necrosis factor (TNF-α) and c-reactive protein (CRP) was evaluated. Results: prevalence of obesity by the %BF was 10.3 % in males and 40.4 % in females. The cut-off points for the WHtR were 0.50 for females and 0.51 for males, with an AuC of 0.90 (95 % CI: 0.88-0.92) and 0.93 (95 % CI: 0.90-0.97). There was an association of elevated WHtR with higher levels of IL-6 and CRP (p < 0.05). Conclusion: the predictive capacity of WHtR for obesity was excellent. Elevated values of the WHtR were associated with early inflammatory markers. This study contributed to the identification of cut-off points for simple and low-cost anthropometric indicators. (AU)

Introducción: la obesidad aumenta las moléculas inflamatorias y el riesgo cardiovascular incluso en poblaciones jóvenes. Se están investigando nuevos indicadores, incluida la relación cintura-altura (RCE) para predecir la obesidad y la relación con los marcadores inflamatorios en la infancia y la adolescencia. Objetivo: identificar los puntos de corte de la RCE para determinar la obesidad y su asociación con marcadores inflamatorios en adolescentes de São Luís, estado de Maranhão, Brasil. Métodos: se trata de un estudio transversal con 2.209 adolescentes de 18 y 19 años pertenecientes a la tercera etapa de la cohorte de nacimiento denominada “RPS”, realizado en 2016. Se identificó el área total bajo la curva ROC (AuC) para evaluar la capacidad predictiva del RCE en relación al porcentaje de grasa corporal (%GC), obtenido a través del pletismografía por desplazamiento de aire (PDA). Se evaluó la asociación de la RCE con los marcadores inflamatorios interleucina-6 (IL-6), factor de necrosis tumoral (TNF-α) y proteína C reactiva (PCR). Resultados: se halló una prevalencia de obesidad por %GC del 10,3 % en hombres y 40,4 % en mujeres. Los puntos de corte para la RCE fueron 0,50 para mujeres y 0,51 para hombres, con un AuC de 0,90 (IC 95 %: 0,88-0,92) y 0,93 (IC 95 %: 0,90-0,97). Hubo una asociación de RCE de nivel superior con niveles más altos de IL-6 y PCR (p < 0,05). Conclusión: la capacidad de predicción de la RCE para la obesidad fue excelente y los valores elevados de RCE se asociaron con marcadores inflamatorios tempranos. Este estudio contribuyó a la identificación de puntos de corte para indicadores antropométricos simples y de bajo coste. (AU)

Cornus iridoid glycoside alleviates sepsis-induced acute lung injury by regulating NF-kB and Nrf2/HO-1 pathways

Background: Sepsis-induced acute lung injury (ALI) is a syndrome associated with inflamma-tion. Cornus iridoid glycoside (CIG), a bioactive component isolated from Corni Fructus, exhibits anti-inflammatory activities. However, the function and underlying mechanisms of CIG in mice with sepsis-induced ALI remain elusive.Methods: The sepsis-elicited ALI model of mice was established by the induction of cecal ligation and puncture (CLP). The wet/dry (W/D) ratio of lung tissues was examined, and the pathological alterations were determined by hematoxylin and eosin staining. The messenger RNA (mRNA) expressions and serum levels of Interleukin (IL)-1Beta IL-6, and tumor necrosis factor-alfa(TNF-alpha) were measured by reverse transcription-quantitative polymerase chain reaction and enzyme-linked immunosorbent serologic assay, respectively. The concentrations of malondial-dehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were assessed by biochemical kits. In addition, the relative protein levels of p-p65, p65, phosphorylated-nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (p-IκBalpha), IκBalpha, nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) gene were analyzed by Western blotting analysis.Results: CLP enhanced W/D ratio and aggravated pathological changes and scores in mice, which were obviously alleviated by the two concentrations of CIG treatment. CIG treatment notably decreased the CLP-induced mRNA expressions and serum levels of IL-1Beta, IL-6, TNF-alpha, and MDA, but enhanced the decreased concentrations (caused by CLP) of SOD and GSH-Px. Moreover, CIG treatment significantly decreased the ratios of p65/p-p65 and IκBα/p-IκBalpha caused by CLP, but...(AU)

Temporal specificity of IL-6 knockout in enhancing the thermogenic capability of brown adipose tissue

Although interleukin-6 (IL-6) has been regarded as a homeostatic regulator of fat metabolism, its role in brown adipose thermogenesis remains to be further clarified. By using wild-type (WT) and IL-6-knockout (KO) mice, this study aims to investigate whether IL-6 regulates the thermogenic capability of brown adipose tissue (BAT) at both young and elderly stages. We demonstrated that IL-6 KO enhances BAT thermogenesis at a young age, as evidenced by the increased mRNA and protein expression levels of thermogenic genes, and the elevated interscapular surface temperature. The IL-6-KO enhancement of BAT thermogenesis is associated with improved respiratory exchange ratio (RER) and glucose homeostasis at young stages. However, these improvements disappear in elderly KO mice, which is likely attributable to the highly increased expression of other inflammatory cytokines, such as Tnfα, Il-1β, and Il-10. Our findings indicate that the lack of IL-6 has a temporal-specific contribution to the promotion of BAT thermogenesis. (AU)

Analysis of cardiovascular disease factors on SARS-CoV-2 infection severity

Background:At present, COVID-19 is a global pandemic and is seriously harmful to humans. In this retrospective study, the aim was to investigate the interaction between CVD and COVID-19.Methods:A total of 180 patients diagnosed with COVID-19 in Yichang Central People's Hospital from 29 January to 17 March 2020 were initially included. The medical history, clinical manifestations at the time of admission, laboratory test results, hospitalization time and complications were recorded. According to the medical history, the patients were assigned to the nonsevere group with non-CVD (n=90), the nonsevere group with CVD (n=22), the severe group with non-CVD (n=40) and the severe group with CVD (n=28).Results:In the severe group, compared with non-CVD patients, CVD patients had a significantly higher incidence of fever (P<0.05). However, compared with the nonsevere group, the severe group had significantly higher proportions of patients with hypertension, type 2 diabetes mellitus, CHD and HF (all P<0.05). Among the patients with nonsevere COVID-19, the WBC count and the levels of IL-6, CRP, D-dimer, NT-proBNP, and FBG were significantly higher and the Hb level was significantly lower in the CVD patients than in the non-CVD patients (all P<0.05). However, among the patients with severe COVID-19, only the level of NT-proBNP was significantly higher in CVD patients than in non-CVD patients (P<0.05). In addition, the WBC count and the levels of IL-6, CRP, D-dimer, CKMB, ALT, AST, SCR, NT-proBNP, and FBG were significantly higher and the Hb level was significantly lower in the severe group than in the nonsevere group (all P<0.05). (AU)

Antecedentes:La infección por SARS-CoV-2 está provocando graves consecuencias en la humanidad. El objetivo de este estudio retrospectivo fue investigar el impacto de las enfermedades cardiovasculares (ECV) en la gravedad de dicha infección.Métodos:Entre el 29 de enero y el 17 de marzo de 2020, se diagnosticaron 180 pacientes con neumonía por SARS-CoV-2 en el Hospital Popular Central de Yichang. Se registraron los antecedentes, manifestaciones clínicas, resultados de laboratorio, tiempo de hospitalización y complicaciones. Los pacientes se dividieron en cuatro grupos: 1) infección no grave sin ECV (n=90), 2) infección no grave con ECV (n=22), 3) infección grave sin ECV (n=40) y 4) infección grave con ECV (n=28).Resultados:La prevalencia de fiebre en los pacientes con ECV fue significativamente mayor que en aquellos sin ECV (P<0,05). Sin embargo, en comparación con los pacientes no graves, la proporción de pacientes con hipertensión, diabetes mellitus tipo 2, cardiopatía coronaria e insuficiencia cardíaca en los pacientes graves fue significativamente mayor (p<0,05). Los niveles de recuento de leucocitos, IL-6, PCR, dímero D, NT-proBNP y glucemia en ayunas (GA) en pacientes con ECV fueron significativamente mayores que en los de pacientes sin ECV, aunque los niveles de Hb fueron significativamente menores que los de los pacientes sin ECV (p<0,05). Sin embargo, los valores de NT-proBNP en pacientes con ECV fueron significativamente mayores que en los pacientes sin ECV (P<0,05). (AU)

Polyphyllin I alleviates lipopolysaccharide-induced inflammation reduces pyroptosis in BEAS-2B and HPAEC cells by inhibiting NF-KB signaling

Polyphyllin I is an active steroidal saponin isolated from Paris polyphylla with anti-cancer and anti-inflammatory properties. The present study investigates the role of polyphyllin I in acute lung injury. Firstly, the human bronchial epithelial cells (BEAS-2B) and human pulmonary artery endo-thelial cells (HPAEC) were stimulated with increasing concentrations of lipopolysaccharide at 2, 5, and 10 μg/mL. The treatment with lipopolysaccharide reduced the cell viabilities of BEAS-2B and HPAEC, downregulated superoxide dismutase (SOD) and glutathione (GSH), and up-regulated myeloperoxidase (MPO) and malondialdehyde (MDA). Moreover, the levels of TNF-α, I L-1β, and IL-6 were also up-regulated in lipopolysaccharide-treated BEAS-2B/HPAEC cells. Secondly, the lipopolysaccharide-treated cells were then incubated with different concentrations of polyphyl-lin I. Incubation with polyphyllin I enhanced the cell viabilities of lipopolysaccharide-treated BEAS-2B/HPAEC, up-regulated levels of SOD and GSH, and reduced MPO and MDA. Moreover, polyphyllin I reduced TNF-α, I L-1β, and IL-6 in lipopolysaccharide-treated BEAS-2B/HPAEC cells. Thirdly, the up-regulation of GSDMD-N, pro-caspase-1, and cleaved caspase-1 proteins in lipo-polysaccharide-treated BEAS-2B/HPAEC cells were decreased by polyphyllin I. Polyphyllin I increased the protein expression of GSDMD-D in the lipopolysaccharide-treated BEAS-2B/HPAEC cells, and inhibited the translocation of GSDMD from cytoplasm to plasma membrane. Lastly, polyphyllin I reduced the expression of p-p65 in lipopolysaccharide-treated BEAS-2B/HPAEC cells. The over-expression of p65 counteracted with the inhibitory effects of polyphyllin I on oxi-dative stress and inflammation in lipopolysaccharide-treated BEAS-2B. In conclusion, polyphyllin (AU)

Correlation analysis of TGF-β1, MMP-9, TIMP-1, IL-1, IL-4, IL-6, IL-17, and TNF-α in refractory chronic rhinosinusitis: A retrospective study

Objective: To investigate the potential correlation of transforming growth factor-β (TGF-β), matrix metalloprotein 9 (MMP-9), tissue inhibitor of metalloproteinases 1 (TIMP-1), Interleukin 1 (IL-1), IL-4, IL-6, IL-17, and tumor necrosis factor alpha (TNF-α) in refractory chronic rhinosinusitis.Methods: A total of 150 participants were retrospectively included in this study from August 2018 to February 2020. The people enrolled were equally allocated into refractory group (patients with refractory chronic rhinosinusitis), chronic group (patients with chronic rhinosi-nusitis), and control group (normal people). The level of TGF-β1, MMP-9, TIMP-1, IL-1, IL-4, IL-6, IL-17, and TNF-α were recorded. The unconditional multivariate binary logistic regression was used to analyze the factors affecting refractory chronic rhinosinusitis.Results: The Davos score, T&T olfactometer threshold test, and Lund-Mackay CT scores in refractory group were significantly higher than the chronic group (P<0.05). The level of TGF-β1, MMP-9, TIMP-1, IL-1, IL-4, IL-6, IL-17, and TNF-α in the refractory group were significantly higher than the chronic group and the control group (all P<0.05). Similarly, the level of the above mentioned indexes in the chronic group were significantly higher than the control group (P<0.05). The Davos score, T&T olfactometer threshold test score, Lund-Mackay CT score, and the level of TGF-β1, MMP-9, TIMP-1, IL-1, IL-4, IL-6, IL-17, and TNF-α positively correlated with refractory chronic rhinosinusitis. Moreover, the unconditional multivariate binary logistic regression showed that the influencing factors of refractory chronic rhinosinusitis included TGF-β1, MMP-9, TIMP-1, IL-1, IL-4, IL-6, IL-17, and TNF-α.Conclusion: The findings of the present study provide evidence for TGF-β1, MMP-9, TIMP-1, IL-4, IL-6, IL-17, and TNF-α as the influencing factors of refractory chronic rhinosinusitis (AU)

El polimorfismo de un solo nucleótido rs1800795 en el gen IL6 no está asociado con el glaucoma primario de ángulo abierto en la población mexicana / The rs1800795 single nucleotide polymorphism in the IL6 gene is not associated with primary open angle glaucoma in Mexican population

Objetivo La interleucina 6 (IL-6) es una citoquina proinflamatoria con efectos pleiotrópicos que se ha relacionado con el glaucoma primario de ángulo abierto (GPAA) debido a su efecto particular de protección de las células ganglionares de la retina (CGR) contra la apoptosis. Se han asociado diferentes polimorfismos de un solo nucleótido (PSN) con el GPAA. El objetivo de este estudio fue determinar si existe una asociación entre el PSN de IL-6 rs1800795 (−174 G>C) y un mayor riesgo de padecer GPAA en la población mexicana occidental. Métodos Se incluyeron 165 pacientes mestizos mexicanos no emparentados con GPAA y 108 sujetos de control. Se extrajo el ADN genómico de los leucocitos y se purificó, seguido de la genotipificación y la amplificación por reacción en cadena de la polimerasa (PCR) con sondas TaqMan® Biosystem®. Se evaluó la diversidad alélica y genotípica entre los casos y los sujetos de control. Resultados No hubo asociación estadísticamente significativa entre las frecuencias alélicas y genotípicas, ni con modelos de asociación genética dominante ni recesiva (p>0,05). Conclusiones Aunque existe un papel de la IL6 en la fisiopatología del GPAA, nuestros resultados descartan la asociación entre la IL-6 y el PSN rs1800795 mostrando no ser un índice de mayor riesgo de GPAA en la población mexicana (AU)

Purpose Interleukin-6 (IL-6) is a proinflammatory cytokine with pleiotropic effects which has been related to primary open angle glaucoma (POAG) due to its particular effect of protecting the retinal ganglion cells (RGc) from the apoptosis. Different single nucleotide polymorphisms (SNP) have been associated with POAG. The aim of this study was to determine whether an association between IL-6 rs1800795 (−174 G>C) SNP and a higher risk for POAG is present in western Mexican population. Methods One hundred and sixty-five unrelated Mexican mestizo patients with POAG and 108 control subjects were included. Genomic DNA was extracted from leukocytes and purified, followed by genotyping and amplification by polymerase chain reaction (PCR) with Taqman Biosystem probes. Allelic and genotypic diversity was evaluated between cases and control subjects. Results There was no statistically significant association between allele and genotype frequencies, neither with dominant nor recessive genetic association models (P>.05). Conclusion Even though there is a role of IL6 in the pathophysiology of POAG, our results ruled out the association between IL-6 and the rs1800795 SNP showing not to be an index of higher risk for POAG in Mexican population (AU)

Marcadores aterogénicos y de inflamación en pacientes con diabetes mellitus tipo 2 / Inflammation and atherogenic markers in patients with type 2 diabetes mellitus

La diabetes mellitus tipo 2 (DMT2) es una enfermedad caracterizada por un estado inflamatorio crónico en la que algunos marcadores como las concentraciones de lípidos se han encontrado frecuentemente alterados. Se han descrito otros marcadores de inflamación alterados como las interleucinas 6, 8 y el factor de necrosis tumoral, sin embargo, existe poca información acerca del comportamiento del índice neutrófilo/linfocito (INL), la relación plaquetas/linfocitos (RPL) y el índice monocitos/linfocitos (IML), los coeficientes lipídicos y el índice aterogénico en pacientes con DMT2. Objetivo: Describir los parámetros aterogénicos y de inflamación en un grupo de pacientes con DMT2. Materiales y métodos: Se incluyeron y analizaron los antecedentes clínicos (antecedentes de la enfermedad, comorbilidad, tabaquismo y otras variables relevantes), así como parámetros hematológicos, bioquímicos y antropométricos de 42 pacientes, y se calcularon y evaluaron los coeficientes aterogénicos e índices de inflamación. Resultados: Se encontraron concentraciones elevadas de citocinas proinflamatorias IL-6 e IL-8, factor de necrosis tumoral-α y elevado INL. El 88% de los pacientes fueron clasificados como de alto riesgo de acuerdo con el índice aterogénico. Los pacientes exfumadores exhibieron niveles menores de IL-8 y niveles más altos de INL comparados con los que nunca han fumado. Conclusión: La evaluación de marcadores aterogénicos y de inflamación tales como el índice aterogénico, IL-8 y la INL permiten identificar a un subgrupo de pacientes con un alto riesgo de complicaciones graves y mortalidad. (AU)

Type two diabetes mellitus (T2DM) is characterized by a chronic inflammation status. Altered markers such as lipid concentrations are usually found in this disease. Elevated inflammation markers have been described such as cytokines (interleukin 6, tumour necrosis factor-alpha, and IL-8). However, there is a lack of information about the behaviour of the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), lipid coefficients, and atherogenic index in T2DM. Objective: To describe the atherogenic and inflammation parameters in a group of patients with T2DM. Materials and methods: 42 patients with T2DM were included, all patients were surveyed on clinic history (disease history, comorbidity, smoking, and other relevant variables), measurements of haematological, biochemical, and anthropometric parameters were taken and atherogenic coefficients and inflammation ratios were calculated. Results: Inflammation markers such as interleukin 6 and 8, necrosis tumour factor, and NLR were elevated. Of the patients, 88% were classified as high risk according to the atherogenic index. Former smokers had lower levels of IL-8 and higher NLR than non-smokers. Conclusion: The atherogenic and inflammation markers such as atherogenic index, IL-8, and NLR make it possible to identify a subgroup of patients that are at risk of severe complications and mortality. (AU)

Resveratrol enhanced chemosensitivity by reversing macrophage polarization in breast cancer

BackgroundResveratrol, a naturally occurring polyphenolic compound, has been shown to inhibit cancer growth by targeting several cancer-related signalling pathways. In the tumor microenvironment (TME), tumor-associated macrophages (TAMs) are the most abundant leukocyte population that are associated with poor prognosis in over 80% of breast cancer cases. However, little is known about the effect of resveratrol in the TME.MethodsIn this study, MDA-MB-231(MB231), cisplatin resistance MDA-MB-231 (cisR), and T47D were used to examine the antitumor effect of resveratrol. The effectiveness of resveratrol, together with cisplatin as breast cancer treatment was investigated in vivo. Gene expressions of M1 (iNOS and CXCL10) and M2 (ARG1, CD163 and MRC1) markers in differentiated macrophages derived from THP-1 cells were examined to investigate the effect of resveratrol on TAM polarization in breast cancer progression.ResultsOur results demonstrated that resveratrol significantly reduced cell proliferation and enhanced chemosensitivity in breast cancer cells by inhibiting production of IL-6 and STAT3 activation. Treatment of resveratrol increased CXCL10 (M1 marker) expression. Further, resveratrol decreased IL-6 levels in LPS-treated differentiated macrophages. The use of resveratrol with cisplatin inhibited suppressed tumor growth when compared with cisplatin alone.ConclusionThis study revealed that resveratrol inhibited breast cancer cell proliferation by promoting M1/M2 macrophage polarization ratio and suppressing IL-6/pSTAT3 pathway.

Revisión sistemática y metaanálisis de inhibidores de interleucina-6 para reducir la mortalidad en pacientes hospitalizados con COVID-19 / Systematic review and meta-analysis of interleulin-6 inhibitors in reducing mortality for hospitalized patients with COVID-19

Objetivo: Un año después de la declaración de la pandemia porSARS‑CoV-2, solo dexametasona había mostrado claramente una reducciónde la mortalidad en pacientes hospitalizados por COVID-19. Losresultados de los inhibidores de interleucina 6 son diversos y poco claros.El objetivo de este trabajo es revisar y analizar el efecto de tocilizumaby sarilumab sobre la supervivencia de los pacientes en este escenario.Método: La revisión sistemática siguió las recomendaciones de PRISMA.Se realizó una búsqueda sistemática en Medline, Embase y medRxiv paraidentificar ensayos controlados aleatorizados con tocilizumab o sarilumaben pacientes hospitalizados con COVID-19. Se recopilaron los datosde mortalidad de pacientes críticos y no críticos y se llevó a cabo unmetaanálisis de efectos aleatorios (Der Simonian-Laird) para ambos subgruposy para toda la población, usando el software MAVIS v. 1.1.3. Lasimilitud y homogeneidad entre los ensayos fue evaluada.Resultados: Se identificaron 25 y 23 artículos en Medline y Embase,respectivamente; cinco eran ensayos con tocilizumab y/o sarilumab; seidentificaron dos más en medRxiv. En total, siete ensayos clínicos aleatorizadoscumplieron los criterios de inclusión. Posteriormente, se prepublicóotro ensayo que cumplía los criterios de inclusión y se incorporó absoalanálisis. El metaanálisis, con ocho ensayos clínicos aleatorizados y6.340 pacientes, mostró un beneficio sobre la mortalidad para los inhibidoresde interleucina-6 (hazard ratio 0,85; intervalo de confianza al 95%0,74-0,99), con baja heterogeneidad (I2 = 7%), pero reducida similitudentre los estudios. Los resultados no mostraron diferencias entre pacientescríticos y no críticos. Un análisis de sensibilidad excluyendo estudios heterogéneoso no similares mostró resultados diferentes, sin beneficio y conbaja precisión del resultado en pacientes no críticos.

Objective: One year after the declaration of the SARS-CoV-2 pandemic,only dexamethasone has clearly shown a reduction in mortality forCOVID-19 hospitalized patients. For interleukin-6 inhibitors, results arevariable and unclear. The objective was to review and analyze the effectof tocilizumab and sarilumab on survival in this setting.Method: The PRISMA statements were fulfilled for the systematic review.A systematic search in Medline, Embase and medRxiv was conductedto identify randomized controlled trials with tocilizumab or sarilumab inhospitalized patients with COVID-19. Mortality data from non-critical andcritical patients were extracted. A random-effects (DerSimonian-Laird)meta-analysis was performed for both subgroups and the whole populationusing MAVIS software v. 1.1.3. Similarity and homogeneity amongtrials were assessed.Results: Twenty-five and 23 articles were identified in Medline andEmbase, respectively, five were trials with tocilizumab and/or sarilumab;two more were identified at medRxiv. Seven randomized clinical trialsfulfilled the inclusion criteria. Another trial was pre-published and includedpost-hoc. The meta-analysis, with eight randomized clinical trialsand 6,340 patients, showed a benefit on mortality for interleukin-6 inhibitor (hazard ratio 0.85; confidence interval 95% 0.74-0.99), lowheterogeneity (I2 = 7%), but a low similarity among studies. The resultsshowed no differences among critical and non-critical patients. A sensitivityanalysis excluding non-similar or heterogeneous studies showeddifferent results, without benefit and with low precision of the result innon-critical patients.