In vitro adhesion and anti-inflammatory properties of Limosilactobacillus fermentum FS-10 isolated from infant fecal sample / Adhesión in vitro y propiedades antiinflamatorias de Limosilactobacillus fermentum FS-10 aislado de muestra fecal infantil

In this study, seven strains of Limosilactobacillus fermentum were isolated from an infant fecal sample and characterized using in vitro studies. Lactobacillus rhamnosus GG was used as a comparison because it is a well-documented commercial probiotic. The isolates were tested for attributes such as acid and phenol tolerance, bile salt hydrolase (BSH) activity, and antibiotic sensitivity. One isolate, L. fermentum FS-10, displayed enhanced cell surface hydrophobicity (> 85%) and mucin adhesion. Mucin-binding helps colonization in the gut. The immunomodulatory property of L. fermentum FS-10 was evaluated by determining the modulation of pro- and anti-inflammatory factors such as tumor necrosis factor-alpha (TNF-α), interleukin (IL)-10, and nitric oxide (NO) in human acute monocytic leukemia (THP-1) cells under inflammatory conditions induced by lipopolysaccharide (LPS). L. fermentum FS-10 potently downregulated the expression of TNF-α and nitric oxide and upregulated IL-10 levels, indicating an anti-inflammatory response. Safety assessment of the strain revealed the absence of genes for virulence factors, toxin production, and antibiotic resistance, potentiating application as a probiotic strain.(AU)

Efectos adversos cutáneos inmunomediados por los anti-TNF: revisión de 30 casos / Immune-Mediated Skin Reactions to Tumor Necrosis α Inhibitors: A Review of 30 Cases

Introducción Los fármacos biológicos inhibidores del factor de necrosis tumoral (TNF) alfa son usados para tratar diferentes enfermedades inflamatorias. A pesar de su adecuado perfil de seguridad, se han descrito reacciones paradójicas asociadas a estos tratamientos. Material y método Se ha realizado una revisión retrospectiva de los pacientes en tratamiento con un anti-TNF que hubiesen presentado una reacción paradójica con afectación cutánea visitados en el Servicio de Dermatología del Hospital Universitari Parc Taulí de Sabadell. Resultados Registramos 30 pacientes en tratamiento con un anti-TNF que desarrollaron un efecto adverso cutáneo inmunomediado en forma de psoriasis (90%), alopecia (6,7%) o dermatitis neutrofílica (3,3%). Adalimumab fue el fármaco más implicado (56,7%), seguido de infliximab (40%). La morfología de la reacción psoriasiforme más descrita es la generalizada en placas (62,9%), seguida de la pustulosis palmo-plantar (37%). El 43,3% de los pacientes mantuvieron el anti-TNF, y de ellos el 92,3% obtuvieron una resolución total y parcial. De los 5 pacientes que iniciaron otro anti-TNF, ninguno obtuvo una resolución total. De los 8 pacientes que cambiaron a un tratamiento biológico diferente al anti-TNF, el 62,5% obtuvieron una resolución total o parcial. Discusión La aparición de una reacción paradójica no siempre obliga al cambio de tratamiento biológico, puesto que se ha observado la resolución de las lesiones cutáneas con un tratamiento tópico y/o sistémico adicional en más de la mitad de los pacientes, sin necesidad de suspender el anti-TNF. Si la afectación es grave, se debe plantear el cambio de tratamiento biológico, siendo más eficaz iniciar un fármaco dirigido a una diana terapéutica distinta al anti-TNF (AU)

Background Tumor necrosis factor α (TNF) inhibitors are used to treat different inflammatory diseases. Although these biologics have an adequate safety profile, they have been associated with paradoxical reactions. Material and methods Retrospective review of patients on TNF inhibitor therapy who developed a paradoxical skin reaction and were seen at the dermatology department of Hospital Universitari Parc Taulí in Sabadell, Spain. Results We collected data on 30 patients under treatment with a TNF inhibitor who developed an immune-mediated skin reaction in the form of psoriasis (90%), alopecia (6.7%), or neutrophilic dermatitis (3.3%). The most common drugs involved were adalimumab (56.7%) and infliximab (40%). Psoriasiform reactions mostly manifested as generalized plaques (62.9%) or palmoplantar pustulosis (37%). Thirteen patients (43.3%) continued on the same TNF inhibitor and 12 of them (92.3%) achieved partial or complete resolution of lesions. Five patients were switched to a different TNF inhibitor, but none of them achieved complete resolution. Eight patients were switched to a biologic with a different target, and 5 of them (62.5%) achieved partial or complete resolution. Conclusions Paradoxical reactions during TNF inhibitor therapy do not always require a change of treatment. In our series, the addition of a topical and/or systemic treatment resolved the skin lesions in more than half of the patients, and switching to a drug with a different target was more effective. A change of strategy should be contemplated in more serious cases (AU)

[Translated article] Immune-Mediated Skin Reactions to Tumor Necrosis α Inhibitors: A Review of 30 Cases / Efectos adversos cutáneos inmunomediados por los anti-TNF: revisión de 30 casos

Background Tumor necrosis factor α (TNF) inhibitors are used to treat different inflammatory diseases. Although these biologics have an adequate safety profile, they have been associated with paradoxical reactions. Material and methods Retrospective review of patients on TNF inhibitor therapy who developed a paradoxical skin reaction and were seen at the dermatology department of Hospital Universitari Parc Taulí in Sabadell, Spain. Results We collected data on 30 patients under treatment with a TNF inhibitor who developed an immune-mediated skin reaction in the form of psoriasis (90%), alopecia (6.7%), or neutrophilic dermatitis (3.3%). The most common drugs involved were adalimumab (56.7%) and infliximab (40%). Psoriasiform reactions mostly manifested as generalized plaques (62.9%) or palmoplantar pustulosis (37%). Thirteen patients (43.3%) continued on the same TNF inhibitor and 12 of them (92.3%) achieved partial or complete resolution of lesions. Five patients were switched to a different TNF inhibitor, but none of them achieved complete resolution. Eight patients were switched to a biologic with a different target, and 5 of them (62.5%) achieved partial or complete resolution. Conclusions Paradoxical reactions during TNF inhibitor therapy do not always require a change of treatment. In our series, the addition of a topical and/or systemic treatment resolved the skin lesions in more than half of the patients, and switching to a drug with a different target was more effective. A change of strategy should be contemplated in more serious cases (AU)

Introducción Los fármacos biológicos inhibidores del factor de necrosis tumoral (TNF) alfa son usados para tratar diferentes enfermedades inflamatorias. A pesar de su adecuado perfil de seguridad, se han descrito reacciones paradójicas asociadas a estos tratamientos. Material y método Se ha realizado una revisión retrospectiva de los pacientes en tratamiento con un anti-TNF que hubiesen presentado una reacción paradójica con afectación cutánea visitados en el Servicio de Dermatología del Hospital Universitari Parc Taulí de Sabadell. Resultados Registramos 30 pacientes en tratamiento con un anti-TNF que desarrollaron un efecto adverso cutáneo inmunomediado en forma de psoriasis (90%), alopecia (6,7%) o dermatitis neutrofílica (3,3%). Adalimumab fue el fármaco más implicado (56,7%), seguido de infliximab (40%). La morfología de la reacción psoriasiforme más descrita es la generalizada en placas (62,9%), seguida de la pustulosis palmo-plantar (37%). El 43,3% de los pacientes mantuvieron el anti-TNF, y de ellos el 92,3% obtuvieron una resolución total y parcial. De los 5 pacientes que iniciaron otro anti-TNF, ninguno obtuvo una resolución total. De los 8 pacientes que cambiaron a un tratamiento biológico diferente al anti-TNF, el 62,5% obtuvieron una resolución total o parcial. Discusión La aparición de una reacción paradójica no siempre obliga al cambio de tratamiento biológico, puesto que se ha observado la resolución de las lesiones cutáneas con un tratamiento tópico y/o sistémico adicional en más de la mitad de los pacientes, sin necesidad de suspender el anti-TNF. Si la afectación es grave, se debe plantear el cambio de tratamiento biológico, siendo más eficaz iniciar un fármaco dirigido a una diana terapéutica distinta al anti-TNF (AU)

Artritis reumatoide / Rheumatoid arthritis

La artritis reumatoide (AR) es una enfermedad inflamatoria crónica multisistémica de etiología desconocida y de naturaleza autoinmune que afecta predominantemente a las articulaciones periféricas de forma simétrica. Aunque se ha avanzado mucho en la comprensión de su fisiopatología, su etiología sigue siendo desconocida. El factor de necrosis tumoral (TNF)-α y la interleucina (IL)-6, juegan un papel importante en la patogénesis y la perpetuación de la inflamación en la AR. La presencia de anticuerpos antipéptidos citrulinados ayuda en el diagnóstico en pacientes con poliartritis indiferenciadas y se relaciona con una evolución más agresiva de la AR. La evolución natural de la AR causa deformidad articular y discapacidad, además de una reducción de la esperanza de vida, por aumento del riesgo cardiovascular, afectación pulmonar, infecciones, iatrogenia o tumores. El diagnóstico precoz y la utilización de fármacos dirigidos que buscan la remisión temprana han mejorado sustancialmente el pronóstico de la AR (AU)

Rheumatoid arthritis (RA) is a chronic inflammatory multisystemic disease of unknown etiology and autoimmune nature that predominantly affects peripheral joints in a symmetrical fashion. Although much progress has been made in understanding the pathophysiology of RA, its etiology remains unknown. Tumor necrosis factor (TNF)-α and interleukin (IL)-6 play the important roles in the pathogenesis and maintenance of inflammation in RA. The presence of anti-citrullinated peptide antibodies aids in the diagnosis in patients with undifferentiated polyarthritis and is associated with a more aggressive RA. The natural history of RA causes joint deformity and disability, as well as reduced life expectancy, both due to increased cardiovascular risk, pulmonary involvement, infections, iatrogenesis or tumors. Early diagnosis and the use of targeted drugs to induce early remission have improved the RA prognosis (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)

The efficacy of hydrogel containing zinc oxide-loaded and minocycline serum albumin nanopartical in the treatment of peri-implantitis

Background: We conducted this animal study to assess the efficacy of the novel hydrogel containing zinc oxide-loaded and minocycline serum albumin nanoparticals (Mino-ZnO@Alb NPs) on peri-implantitis in an experimental mouse model. Material and methods: Mino-ZnO@Alb NPs was prepared as previously reported. The peri-implantitis model was successfully established in rats, and the rats were divided into three groups randomly: Mino-ZnO@Alb NPs (Mino-ZnO) group, minocycline group, and untreated group. Four weeks later, clinical and radiographic assessments were performed to evaluate soft tissue inflammation and bone resorption level. Histologic analysis was performed to estimate the amount of remaining supporting bone tissue (SBT) around implants. ELISA tests were used to determine the concentration of inflammation factor interleukin-1-beta (IL-1β) and anti-inflammation factor tumor necrosis factor-alpha (TNF-α) around implants. Results: After one month, the Mino-ZnO group showed better results than the other two groups in regards to the results of bleeding on probing, probing pocket depth, bleeding index and gingival index. X-ray showed that SBT at mesial and distal sites around implants in the other two groups was significantly lower compared with that of Mino-ZnO group. The quantity of osteoclasts in peri-implant tissues of the Mino-ZnO group was less than that in the minocycline and untreated groups. IL-1β in the Mino-ZnO group was lower than that in the other two groups. TNF-α level was the opposite. Conclusions: Mino-ZnO@Alb NPs can effectively treat peri-implantitis and promote soft tissue healing, and may act as a promising product. (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)

Pro-inflammatory cytokines in patients with low back pain: A comparative study / Citoquinas proinflamatorias en pacientes con dolor lumbar: un estudio comparativo

Introduction and objectives: There are controversial results regarding the value of serum IL-8 and TNFα in patients with non-specific low back pain. This study aimed to compare pro-inflammatory cytokines between patients with non-specific back pain and pain-free controls. Materials and methods: We conducted a case–control study including 106 participants: 46 patients with chronic non-specific low back pain (G1) and 60 pain-free controls (G0). The interleukin (IL-)6, IL-8, IL-17, IL-23, IL-22, and Tumor necrosis factor α (TNFα) were measured. We collected demographic and clinical data, including age, gender, low back pain duration and radicular pain. The pain degree was assessed using the Visual Analogic Scale. Results: The mean age was 43.17±8.7 years in G1. Radicular pain was found in 37 cases with a Visual Analogic Scale of 3.03±2.5mm. The magnetic resonance imaging was performed in (G1), showing disk herniation and degenerative disk disease in 54.3% (n=25) and 45.7% of cases (n=21), respectively. The IL-8 was higher in G1 (18.84±44.64 versus 4.34±1.23pg/mL, p:0.033). IL-8 levels correlated with TNFα (0.942, p<10–3), IL-6 (0.490, p=0.011) and Visual Analogic ScaleRadicular-pain (r:0.297, p:0.047). IL-17 was higher in patients with restricted lumbar spine mobility (9.64±20.77 versus 1.19±2.54pg/mL, p:0.014). Conclusions: Our results provide evidence that IL-8 and TNFα play a role in low back pain and radicular pain due to disk degeneration or herniation. These findings could potentially be used by future studies to develop new non-specific low back pain therapeutic strategies.(AU)

Introducción y objetivos: Existen resultados controvertidos en cuanto al valor de la interleucina (IL) 8 y el factor de necrosis tumoral α (TNFα) séricos en pacientes con lumbalgia inespecífica. Este estudio tuvo como objetivo comparar las citoquinas proinflamatorias entre pacientes con dolor de espalda inespecífico y controles sin dolor. Materiales y métodos: Realizamos un estudio de casos y controles que incluyó a 106 participantes: 46 pacientes con dolor lumbar crónico inespecífico (G1) y 60 controles sin dolor (G0). Se midieron las IL-6, IL-8, IL-17, IL-23, IL-22 y el TNFα. Recopilamos datos demográficos y clínicos, incluidos la edad, el sexo, la duración del dolor lumbar y el dolor radicular. El grado de dolor se evaluó mediante la escala analógica visual. Resultados: La edad media fue de 43,17±8,7 años en G1. Se encontró dolor radicular en 37 casos con una escala analógica visual de 3,03±2,5mm. La resonancia magnética se realizó en G1, mostrando hernia discal y enfermedad discal degenerativa en el 54,3% (n=25) y el 45,7% de los casos (n=21), respectivamente. La IL-8 fue mayor en G1 (18,84±44,64 versus 4,34±1,23pg/ml, p=0,033). Los niveles de IL-8 se correlacionaron con TNFα (0,942, p<10−3), IL-6 (0,490, p=0,011) y escala visual analógicadolor radicular (r=0,297, p=0,047). IL-17 fue mayor en pacientes con movilidad restringida de la columna lumbar (9,64±20,77 versus 1,19±2,54pg/ml, p=0,014). Conclusiones: Nuestros resultados proporcionan evidencia de que la IL-8 y el TNFα juegan un papel en el dolor lumbar y en el dolor radicular debido a la degeneración o a hernia discal. Estos hallazgos podrían potencialmente ser utilizados por estudios futuros para desarrollar nuevas estrategias terapéuticas no específicas para el dolor lumbar.(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)

Nrf2 regulates the expression of NOX1 in TNF-a-induced A549 cells

Acute lung injury causes severe inflammation and oxidative stress in lung tissues. In this study, we analyzed the potential regulatory role of nuclear factor erythroid-2-related factor 2 (Nrf2) on NADPH oxidase 1 (NOX1) in tumor necrosis factor-α (TNF-α)-induced inflammation and oxidative stress in human type II alveolar epithelial cells. In this study, A549 cells were transfected with Nrf2 siRNA and overexpression vectors for 6 h before being induced by TNF-α for 24 h. TNF-α upregulated the expression of NOX1 and Nrf2 in A549 cells. Furthermore, overexpression of Nrf2 could reduce TNF-α-induced NF-κB mRNA and protein expression after transfection with the Nrf2 siRNA vector, and the levels of IL-6, IL-8, ROS, and malondialdehyde (MDA) in TNF-α-induced A549 cells increased, while the level of total antioxidation capability (T-AOC) decreased. On the other hand, the overexpression of Nrf2 decreased the levels of IL-6, IL-8, ROS, and MDA, while increasing T-AOC. The mRNA and protein levels of NOX1 were dramatically increased by TNF-α, while those changes were notably suppressed by Nrf2 overexpression. Further studies demonstrated that Nrf2 suppressed NOX1 transcription by binding to the -1199 to -1189 bp (ATTACACAGCA) region of the NOX1 promoter in TNF-α-stimulated A549 cells. Our study suggests that Nrf2 may bind to and regulate NOX1 expression to antagonize TNF-α-induced inflammatory reaction and oxidative stress in A549 cells (AU)

Kaempferitrin alleviates LPS-induced septic acute lung injury in mice through downregulating NF-kB pathway

Background: Acute lung injury (ALI) causes severe and uncontrolled pulmonary inflammation and has high morbidity in dying patients. Objective: This study aimed to evaluate the potential function of Kaempferitrin (Kae) and uncover its mechanisms in ALI. Material and Methods: We evaluated the role of Kae in ALI through the lipopolysaccharide (LPS)-induced histopathological changes, lung wet/dry (W/D) ratio, total bronchoalveolar lavage fluid (BALF) cells count, pulmonary inflammation, and the levels of interleukin (IL)-6, tumor necrosis factor-α (TNF-α), and IL-1β. The effect of Kae on NF-κB signaling pathway was discovered through the protein expression levels of transcription factors p65, p-p65, IκBα, and p-IκBα by Western blot analysis. Results: The results showed that Kae could improve lung injury by reducing apoptosis, histopathological changes, and lung W/D ratio; more importantly, Kae enhanced the survival of ALI mice. Moreover, Kae relieved inflammation, as it reduced total BALF cells count, and deceased the levels of TNF-α, IL-6, and IL-1β in serum. In addition, Western blot analysis data suggested that Kae could decrease the protein expression levels of transcription factors p65, p-p65, IκB-α, and p-IκB-α, which were promoted by LPS. Conclusion: The results of this study suggested that Kae could relieve LPS-induced ALI in mice and reduce inflammation and apoptosis through NF-κB pathway (AU)

Dihydrokaempferol attenuates LPS-induced inflammation and apoptosis in WI-38 cellsQiao

Background: Globally, pneumonia has been associated as a primary cause of mortality in children aged less than 5 years. Dihydrokaempferol (DHK) has been proposed for being correlated with the process of various diseases. Nevertheless, whether DHK has a role in the progression of infantile pneumonia remains unclear. This study aimed at exploring whether DHK was involved in the progression of infantile pneumonia. Methods: Human fibroblast cells WI-38 were treated with lipopolysaccharide (LPS). The viability of WI-38 cells was measured via Cell counting kit-8. Reverse transcription-quantitative polymerase chain reaction was used to evaluate the levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α). Western blot analysis revealed the protein levels of IL-1β, IL-6, TNF-α, Bax, and cleaved-caspase 3. Flow cytometry was applied for exploring the apoptosis of WI-38 cells. The concentrations of IL-1β, IL-6, and TNF-α were assessed via enzyme-linked-immunosorbent serologic assay. Results: DHK modulated the viability of WI-38 cells in infantile pneumonia. Furthermore, we identified that DHK treatment inversely changed LPS induction-mediated elevation on the levels of inflammation biomarkers. Besides, DHK counteracted LPS-induced production of reactive oxygen species (ROS) in WI-38 cells. DHK also decreased LPS-induced elevation of WI-38 cells apoptosis and mediated the levels of apoptosis-associated indexes. Moreover, modulating sirtuin-1 (SIRT1) protein level was lowered by the induction of LPS, and was reversed by DHK treatment. In addition, DHK counteracted LPS induction-mediated elevation of p-p65 and phosphorylated inhibitor of nuclear factor kappa-B kinase subunit alpha (p-IκBα) protein levels. Conclusion: DHK alleviated LPS-induced WI-38 cells inflammation injury in infantile pneumonia through SIRT1/NF-κB pathway. The results shed light on the implications of DHK on the prevention and treatment of infantile pneumonia (AU)

Coptisine attenuates sepsis lung injury by suppressing LPS-induced lung epithelial cell inflammation and apoptosis

Objective: This study aimed to investigate the functioning and mechanism of coptisine in acute lung injury (ALI). Methods: Murine Lung Epithelial 12 (MLE-12) cells were stimulated with lipopolysaccharide (LPS) to construct an in vitro pulmonary injury model to study the functioning of coptisine in sepsis-induced ALI. The viability of MLE-12 cells was assessed by the cell counting kit-8 assay. The cytokine release of tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), and IL-1β was measured by enzyme-linked-immunosorbent serologic assay. The relative expression levels of TNF-α, IL-6, and IL-1β mRNA were examined by reverse transcription-quantitative polymerase chain reaction. The cell apoptosis of MLE-12 cells was determined by Annexin V/propidium iodide staining and analyzed by flow cytometry. The expressions of apoptosis-related proteins Bax and cleaved Caspase-3 were observed by Western blot analysis. The activation of nuclear factor kappa B (NF-κB) signaling pathway was discovered by the determination of phospho-p65, p65, phospho-nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor alpha (IκBα), and IκBα through Western blot analysis. Results: Coptisine treatment could significantly restore decrease in MLE-12 cell viability caused by LPS stimulation. The release of TNF-α, IL-6, and IL-1β was significantly inhibited by coptisine treatment. Coptisine treatment inhibited MLE-12 cell apoptosis induced by LPS, and also inhibited the expression levels of Bax and cleaved Caspase-3. Coptisine treatment along with LPS stimulation, significantly reduced the protein level of phospho-IκBα, increased the level of IκBα, and reduced phospho-p65–p65 ratio. Conclusion: These results indicated that coptisine attenuated sepsis lung injury by suppressing lung epithelial cell inflammation and apoptosis through NF-κB pathway. Therefore, coptisine may have potential to treat sepsis-induced ALI (AU)

Serum dual-specificity phosphatase 1 reflects decreased exacerbation risk, correlates with less advanced exacerbation severity and lower inflammatory cytokines in children with asthma

Background It is as fact that dual-specificity phosphatase 1 (DUSP1) regulates the T cell activation, pro-allergic response, and inflammation to engage with the pathogenesis of asthma, but its clinical role in children with asthma is unclear. The present study aimed to explore the expression of DUSP1, its association with exacerbation risk, severity, and inflammatory cytokines in children with asthma. Method Around 52 children with asthma-exacerbation, 50 children in asthma-remission, and 50 healthy children were chosen for the study. The serum levels of DUSP1, as well as tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and IL-17 were detected by the enzyme-linked immunosorbent assay. Results The levels of DUSP1 was the highest in healthy children (median (IQR)=34.305 (25.892– 43.693) ng/mL), the second highest in children in asthma-remission (median (IQR)=21.471 (18.581–27.934) ng/mL), and the lowest in children with asthma-exacerbation (median (IQR)=13.982 (7.901–21.624) ng/mL) (P<0.001). At the same time, DUSP1 was also related to decreased asthma risk with area under curve (AUC) (95%CI) of 0.847 (0.780–0.914), and correlated with its lower exacerbation risk with AUC (95%CI) of 0.755 (0.661–0.849). Besides, DUSP1 was negatively linked with exacerbation severity (rs=–0.338, P=0.014), immunoglobulin E (rs=-0.277, P=0.047), TNF-α (rs=-0.423, P=0.002), IL-1β (rs=-0.389, P=0.004), and IL-17 (rs=-0.293, P=0.035), but not related with other disease features in children with asthma-exacerbation. Meanwhile, DUSP1 was only negatively associated with TNF-α (rs=-0.300, P=0.034) and IL-1β (rs=-0.309, P=0.029) in children in asthma-remission. However, no correlation was found in DUSP1 with inflammatory cytokines or other disease features in healthy children (all P>0.05). Conclusion DUSP1 reflects the reduced exacerbation risk, and associates with lower (AU)

Orientin inhibits the progression of fibroblast-like synovial cells in rheumatoid arthritis by regulating MAPK-signaling pathway

Background Natural compounds are found to play an essential role in diverse inflammatory diseases, including rheumatoid arthritis (RA). Orientin, a flavonoid compound, is closely related to diverse pathological processes. Nevertheless, the role of orientin in RA is still unknown. Methods The cell viability was tested through cell counting kit 8 (CCK-8) assay, and the number of cell colonies was calculated via colony formation assay. In addition, flow cytometry assay was employed to detect apoptosis rate in human RA fibroblast-like synoviocytes (RA-FLS). Besides, Transwell assay was introduced to determine cell migratory and invasive abilities. Moreover, the level of cytokines (IL-8, IL-1β, and IL-6) was estimated with quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent serologic assay. Furthermore, western blotting analysis was used to test the protein levels of cleaved-caspase-3, Bax, BCL-2, matrix metalloproteinase (MMP)-2, MMP-9, phosphorylated c-Jun N-terminal kinase, p-P38, and phospho-extracellular signal-related kinase. Results Orientin inhibited cell viability, migration as well as invasion in a concentration- dependent manner in human RA-FLS. Additionally, treatment of orientin facilitated apoptosis and decreased the secretion of cytokines induced by tumor necrosis factor alpha (TNF-α) in human RA-FLS. Moreover, orientin inactivated mitogen-activated protein kinase (MAPK)-related signaling pathway, notably in human RA-FLS. Conclusion These findings confirmed that orientin inhibited human RA-FLS development and decreased TNF-α-induced inflammatory factors, at least partly, by modulating MAPK-signaling pathway, which implied that orientin might be an effective agent for treating RA (AU)

IRX1 ameliorates sepsis-induced acute kidney injury in mice by promoting CXCL14

Background Sepsis-induced acute kidney injury is a general critical complication having high relevance to kidney inflammation. In spite of advances in clinical and critical care, the specific and effective therapies for acute kidney injury are still insufficient. The present study aimed to investigate the protective effect of Iroquois homeobox genes (IRX) on sepsis-induced kidney dysfunction in mice. Methods In order to gain insight into sepsis-related actions in acute kidney injury, the cecal puncture-induced kidney injury animal model was established. The hematoxylin and eosin staining was used to measure the pathology of kidney tissues. The kidney function-related biomarkers, including neutrophil gelatinase-associated lipocalin, creatinine, kidney injury molecule-1, blood urea nitrogen, and inflammatory cytokines, which included tumor necrosis factor α, interleukin 1β (IL-1β), IL-6, and monocyte chemotactic protein 1, were detected by automated biochemical analyzer or their corresponding test kits. The protein expression was measured using Western blot analysis, and the apoptotic rate of kidney tissue was measured by terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Results The present study revealed the protective ability of IRX1 in sepsis-induced acute kidney injury. This study also determined the potential mechanism of IRX1 on sepsis-induced inflammatory response and cell apoptosis. Finally, it highlighted that IRX1 exerted a protective influence on CLP-induced acute kidney injury by suppressing the activation of chemokine (C-X-C motif) ligand 14 (CXCL14). Conclusion To conclude, the results suggest that overexpression of IRX1 could promote survival rate and suppress the CLP-induced apoptosis, inflammatory response, and kidney dysfunction through the activation of CXCL14. IRX1 and CXCL14 are essential to elucidate the mechanism of acute kidney injury. These findings may help to identify the promising targets for clinical sepsis therapy (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)

Momordica charantia extract modulates inflammatory response in human lymphocytes via suppression of TNF-a / El extracto de Momordica charantia modula la respuesta inflamatoria en linfocitos humanos a través de la supresión de TNF-a

Introducción: Momordica charantia L. es ampliamente utilizada para consumo y medicina tradicional debido a sus actividades biológicas. Sin embargo, se sabe poco sobre los efectos del melón amargo en las células sanas. Por lo tanto, nuestro objetivo fue evaluar los efectos del extracto de Momordica charantia en linfocitos humanos aislados, especialmente en aspectos inflamatorios, citotóxicos, genotóxicos y mutagénicos. Método : Para ello se preparó un extracto hidroetanólico con frutos y semillas y se procedió a la identificación y cuantificación fitoquímica. Los linfocitos humanos purificados se expusieron a 12,5; 25; 50 μg/mL de extracto de Momordica charantia durante 24 horas y después de este período. Resultados : Los datos mostraron que el extracto de Momordica charantia no indujo citotoxicidad, alteraciones en la frecuencia de micronúcleos, ni actividad de interleucina-6, interleucina-10 ciclooxigenasa-2 y producción de óxido nítrico; sin embargo, causó daño en el ADN y una disminución de TNF-α en las condiciones experimentales y células aplicadas. Conclusiones : Nuestros datos proponen un proceso antiinflamatorio generado por Momordica charantia mediado por la reducción de TNF-α. (AU)

Introduction: Momordica charantia L. is widely used for consumption and traditional medicine due to its biolog-ical activities. Nevertheless, little is known about the effects of bitter melon on healthy cells. Hence, we aimed to evaluate the effects of Momordica charantia extract in human isolated lymphocytes, especially on inflammatory, cytotoxicity, genotoxicity, and mutagenicity aspects. Method: For this, we prepared a hydroethanolic extract with fruits and seeds and proceeded with phytochemical identification and quantification. The human purified lymphocytes were exposed to 12.5, 25, and 50 μg/mL of Mo-mordica charantia extract for 24h and, after this period. Results: The data showed that the Momordica charantia extract did not induce cytotoxicity, micronucleus frequen-cy alterations, or interleukin-6, interleukin-10 cyclooxygenase-2 activity and the production of nitric oxide; however, it caused DNA damage and a decrease of TNF-α under the experimental conditions and cells applied. Conclusions: Our data propose an anti-inflammatory process generated by Momordica charantia mediated by TNF-α reduction. (AU)

Niveles de fármacos anti-TNFα en pacientes con artritis reumatoide y espondiloartritis / Anti-TNFα Drug Levels in Patients with Rheumatoid Arthritis and Spondyloarthritis

Antecedentes y objetivos: El conocimiento de los niveles de fármacos anti-TNFα puede modificar el tratamiento en pacientes con artritis reumatoide (AR) y espondiloartritis (EspA). Objetivos: Comparar los niveles de anti-TNFα en los pacientes con AR vs. EspA, en diferentes situaciones clínicas. Materiales y métodos: Se realizó un estudio retrospectivo, observacional donde se midieron los niveles de anti-TNFα y la presencia de anticuerpos antifármacos en pacientes seleccionados consecutivamente, utilizando la técnica de ELISA. Resultados: Se estudiaron 53, 73 y 78 pacientes en tratamiento con infliximab, adalimumab y etanercept, respectivamente. Los niveles medios de fármaco en pacientes con dosis estándar fueron: infliximab 2,2μg/ml (1,4-5,2), adalimumab 4,9μg/ml (0,8-8,9) y etanercept 3,1μg/ml (2,3-4,4). No se encontraron diferencias en los niveles fármacos según la actividad de la enfermedad, sin embargo, hubo diferencias en los niveles de etanercept e infliximab según el uso de fármacos modificadores de la enfermedad sintéticos (FAMEsc). Conclusiones: Los niveles de fármacos anti-TNFα se verán modificados por el tratamiento con FAMEsc.(AU)

Background and objectives: Knowledge of the levels of anti-TNFα drugs can modify treatment in patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA).ObjectivesTo compare the levels of anti-TNFα in patients with RA vs SpA, in different clinical situations. Materials and methods: A retrospective, observational study was conducted. Levels of anti-TNFα and the presence of anti-drug antibodies were measured in consecutively selected patients, using the ELISA technique. Results: Fifty-three, 73 and 78 patients treated with infliximab, adalimumab and etanercept were studied, respectively. The median drug levels in patients using standard doses were infliximab 2.2μg/ml (1.4-5.2), adalimumab 4.9μg/ml (0.8-8.9) and etanercept 3.1μg/ml (2.3-4.4). There were no differences in drug levels according to disease activity but we found differences in etanercept and infliximab levels according to DMARD use. Conclusions: Levels of anti-TNFα drugs will change with DMARD treatment.(AU)