Levels Of Inflammatory Factors Research Articles

Efficacy of Pulmicort Respules Combined with Azithromycin in the Treatment of Children with Recurrent Respiratory Tract Infection Caused by Mycoplasmal Pneumonia

Aims/Background The drug treatment of recurrent respiratory tract infection caused by mycoplasma pneumonia (MP) has a complex background, involving the characteristics of pathogens, drug resistance, and multiple treatment methods. This study aimed to analyze the therapeutic effect of pulmicort respules and azithromycin on children with recurrent respiratory tract infection caused by MP. Methods The clinical data of 106 children with recurrent respiratory tract infection caused by MP diagnosed in Huoqiu First People’s Hospital from July 2021 to July 2023 were retrospectively analyzed. Based on different therapeutic methods, 56 children treated with azithromycin were included in the reference group, and 50 children treated with pulmicort respules and azithromycin were included in the observation group. The disappearance time of clinical symptoms, levels of inflammatory factors, immunoglobulin levels, and complications in both groups were observed and compared. Results After treatment, the disappearance time of fever, cough, pulmonary rales, and expectoration was shorter in the observation group, compared with the reference group (p < 0.001). No significant difference was observed in levels of tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2), or interleukin-6 (IL-6) between the two groups on the first day of admission (p > 0.05). After 1 week of treatment, the observation group had significantly higher levels of TNF-α, IL-2, and IL-6 compared with the reference group (p < 0.05). No significant difference was observed in levels of immunoglobulin G (IgG), immunoglobulin A (IgA) and immunoglobulin M (IgM) between the two groups on the first day of admission (p > 0.05). After 1 week of treatment, the observation group had significantly lower levels of IgG, IgA, and IgM than the reference group (p < 0.01). This study revealed that the incidence of complications in the observation group was 16.00%, which was significantly lower than the 37.50% in the reference group (p < 0.05). Conclusion In the short-term clinical treatment, the combination application of pulmicort respules and azithromycin can effectively improve the immune function of children with recurrent respiratory tract infection caused by MP and relieve their clinical symptoms.

Resolvin E1 and Inhibition of BLT2 Signaling Attenuate the Inflammatory Response and Improve One-Lung Ventilation-Induced Lung Injury

ABSTRACT Introduction One-lung ventilation (OLV) is a prevalently used technique to sustain intraoperative pulmonary function. Resolvin E1 (RvE1), a specialized pro-resolving lipid mediator, accelerates the resolution of inflammation in the lungs. However, its therapeutic effects on OLV-induced lung injury remain unclear. Methods We initially developed an OLV rat model and treated it with RvE1. Subsequently, we assessed the wet/dry ratio of the lung tissue, performed hematoxylin and eosin staining, and calculated the ratio of polymorphonuclear cells to white blood cells in the bronchoalveolar lavage fluid. Additionally, we assessed apoptosis, inflammatory factor levels, and lung permeability in the rat lung tissues in the RvE1 treated and untreated groups and explored the molecular mechanisms mediated by RvE1. Results Our results indicated that RvE1 alleviated lung injury and inflammation and improved lung tissue apoptosis and permeability in OLV rats. Moreover, RvE1 suppressed the expression of the BLT1/2 signaling pathway and its ligands. The use of BLT2 and BLT1 inhibitors (LY255283 and U-75302, respectively) enhanced RvE1’s anti-inflammatory effects and reduced lung injury. Furthermore, synergistic treatment with the BLT2 inhibitor and RvE1 provided grater benefits by more effectively inhibiting the NF-kB, p38 MAPK, and ERK pathways. Discussion RvE1 and the inhibition of BLT2 signalling reduce the inflammatory response and mitigate OLV-induced lung injury. These findings suggest a novel therapeutic pathway for managing OLV-related complications.

Prognostic significance of serum inflammatory markers in patients with acute ischemic stroke undergoing revascularization therapy.

This study aimed to evaluate the prognostic significance of serum inflammatory factor levels in patients with acute ischemic stroke undergoing revascularization therapy. The study included 94 patients with acute ischemic stroke who underwent revascularization therapy at our hospital. The primary outcome was the modified Rankin scale (mRS) score assessed three months post-treatment. Patients were categorized into two groups: those with a poor prognosis (mRS score > 2) and those with a good prognosis (mRS score≤2). The patients were divided into two groups based on the type of revascularization treatment received: thrombus extraction or intravenous thrombolysis. Logistic regression analysis was used to identify independent risk factors associated with the prognosis of patients treated with recanalization for acute ischemic stroke. Among the 94 patients, 59 had a good prognosis, and 35 had a poor prognosis. At admission, the patients in the good prognosis group exhibited lower NIHSS scores, shorter hospital stays, fewer previous cardiac events, lower LDL levels, fasting glucose, IL-6, and TNF-a compared to those in the poor prognosis group (all P < 0.05). Logistic regression analysis identified TNF-a (odd ratio (OD), 1.623; 95% confidence interval (CI), 1.282-1.933; P = 0.035) and IL-6 (OD, 1.055; 95% CI, 1.024-1.088, P = 0.023) as independent risk factors for poor prognosis in patients after revascularization. Additionally, pre-hospital NIHSS scores, IL-6, and TNF-a levels were significantly lower in the good prognosis group compared to the poor prognosis group, with these differences being statistically significant. IL-6 and TNF-α may serve as prognostic markers for outcomes following revascularization therapy in patients with acute ischemic stroke, including those receiving intravenous thrombolysis.

Embryonic Lethal Abnormal Visual-Like Protein 1 Aggravates Caerulein-Induced AR42J Cell Injury and Macrophage M1 Polarization to Accelerate Acute Pancreatitis by Upregulating TRAF6.

Tumor necrosis factor receptor-associated factor 6 (TRAF6) has been found to promote the progression of acute pancreatitis (AP). However, its underlying molecular mechanisms in AP need to be further revealed. Caerulein-induced AR42J cells were used to construct AP cell models. Cell viability and apoptosis were measured by Cell Counting Kit 8 assay and flow cytometry. Levels of inflammatory factors and oxidative stress-related markers were assessed. The medium of AR42J cells was collected for coculturing RAW264.7 cells. Macrophage marker CD86+ cell rates were checked with flow cytometry. The levels of TRAF6, embryonic lethal abnormal visual-like protein 1 (ELAVL1), and inducible nitric oxide synthase (iNOS) were examined by Western blot or quantitative real-time polymerase chain reaction. RNA immunoprecipitation assay was performed to evaluate the interaction between ELAVL1 and TRAF6. TRAF6 mRNA stability was tested using actinomycin D treatment. Caerulein treatment suppressed viability, induced AR42J cell apoptosis, inflammation, oxidative stress, and accelerated macrophage M1 polarization. TRAF6 downregulation could alleviate caerulein-induced AR42J cell injury and macrophage M1 polarization. ELAVL1 interacted with TRAF6 to stabilize its expression. Meanwhile, ELAVL1 knockdown relieved caerulein-induced AR42J cell injury and macrophage M1 polarization, while these effects were abolished by TRAF6 overexpression. TRAF6, stabilized by ELAVL1, promoted caerulein-induced AR42J cell injury and macrophage M1 polarization, suggesting that it might accelerate AP9 progression.

Isofraxidin alleviated radiation-induced testicular damage via the Nrf2/HO-1-NLRP3/ASC Axis

OBJECTIVE: Radiotherapy is used to treat patients with tumors; however, radiation (IR)-induced testicular injury, which has no effective treatment approved in clinical practice, significantly influences their prognosis and quality of life. The protective effects and underlying mechanisms of action of isofraxidin (IF) against IR-induced testicular injury were investigated. Methods: A mouse testis injury model was established using 5 Gy irradiation. H&amp;E staining, immunofluorescence staining, and enzyme-linked immunosorbent assay were used to measure DNA damage, apoptosis, inflammatory reactions, and oxidative stress in the testes of mice after irradiation. The effectiveness of IF irradiation on testicular injury was evaluated, and the mechanisms of the related oxidative stress and inflammatory response pathways are discussed. Results: IF can improve IR-induced testicular injury by inhibiting the increased levels of DNA damage, apoptosis rate, oxidative stress, and inflammatory factors. The radioprotective effects of IF on testicular injury are mediated by the stimulation of Nrf2/HO-1 or suppression of NLRP3 inflammasome signaling pathways. In addition, crosstalk between the Nrf2/HO-1 and NLRP3 inflammasome signaling pathways was elucidated, in which the inhibition of the NLRP3 inflammasome was mediated by the activation of Nrf2 signaling with IF upon IR exposure. Conclusion: IF can be a potent radioprotective agent to mitigate testicular damage, and may provide a new therapeutic option to alleviate the side effects of radiotherapy in male patients with tumors.

Evaluating the Biodegradability and Cellular Compatibility of Mg-Zn-Nd Alloy for Vascular Stent Application.

The study is designed to evaluate the corrosion behavior, biocompatibility, and cytotoxicity of a novel magnesium alloy, Mg-2Zn-0.5Nd (ZN20), for potential use as biodegradable scaffolding in cerebrovascular stents. Magnesium alloy (AZ31) and ZN20 are co-cultured with Human Umbilical Vein Endothelial Cells (HUVEC)and human neuroblastoma cell (SH-SY5Y), respectively. The corrosion of AZ31 and ZN20 in different time periods is detected by electron microscope, the effects of AZ31 and ZN20 on the expression level of inflammatory factors are detected by ELISA, the PH value of cells in each group is detected, and the cell proliferation is detected by cck-8. Cell-related apoptosis protein, the expression of Platelet endothelial cell adhesion molecule-1 (CD31)and VE-cad is detected, and the pathological analysis of rat vascular tissue is carried out by HE experiment. In contrast to the AZ31 group, ZN20 exhibits mild, uniform corrosion and does not significantly deter HUVEC proliferation or increase inflammatory markers and In vivo testing reveals better endothelization with ZN20, as demonstrated by higher expression of endothelial markers CD31, and intact endothelial structure group. Western blotting shows favorable expression levels of apoptotic and anti-apoptotic markers in the ZN20 group. ZN20 alloy demonstrates enhanced corrosion resistance, favorable endothelial compatibility, and reduced cytotoxicity, endorsing its safe application in vascular stent use.

Zinc Oxide-Enhanced Copper Sulfide Nanozymes Promote the Healing of Infected Wounds by Activating Immune and Inflammatory Responses.

Bacterial infection and an excessive inflammatory response are two major factors that affect the healing of infected wounds. The zinc oxide/copper sulfide (ZnO-CuS) microspheres (MSs) developed in this work can kill bacteria and resist inflammation. ZnO-CuS exhibits different enzyme-like activities depending on pH. In acidic environments, ZnO-CuS exhibits peroxidase-like (POD-like) activity and can convert hydrogen peroxide (H2O2) into hydroxyl radicals (•OH) for sterilization. Under neutral conditions, ZnO-CuS removes reactive oxygen species (ROS) and can convert excess ROS into water and oxygen. The in vitro results of the antibacterial test demonstrate the pronounced disruption effect of ZnO-CuS on the bacterial biofilm and cell membrane. The transcriptome sequencing results of wounded animal tissue reveal that ZnO-CuS MSs increase the expression of proteins produced by immune cells, and reduce the expression levels of inflammatory factors at the wound site. Therefore, antimicrobial activity and rapid wound healing can be achieved by regulating the immune response and reducing the inflammatory response. The results from hemolysis, routine blood and blood biochemistry analyses demonstrate the excellent biosecurity of the ZnO-CuS MSs.

Gastrodin ameliorates diabetic nephropathy by activating the AMPK/Nrf2 pathway.

Diabetic nephropathy (DN) is a leading cause of end-stage kidney failure, contributing to elevated morbidity and mortality rates in individuals with diabetes. Despite its potential renoprotective effects, the molecular mechanism by which gastrodin (GSTD) impacts DN remains unclear. To investigate this, mice were initially induced with DN via intraperitoneal streptozotocin (STZ) injection (50mg/kg) and subsequently treated with varying doses of GSTD (5, 10, 20mg/kg). Furthermore, the potential molecular mechanism of GSTD in mitigating DN was explored in vivo in conjunction with compound C, an inhibitor of 5'-AMP-activated protein kinase (AMPK). Subsequently, the blood weight, fasting blood glucose levels, and renal injury markers of DN-afflicted mice were assessed. Additionally, renal tissues were subjected to quantitative reverse-transcriptase-polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) to evaluate inflammatory factor levels, colorimetric assays to measure renal malondialdehyde (MDA) levels, and immunoblotting analysis to examine AMPK/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. The results demonstrated that a 6-week GSTD regimen effectively improved metabolic manifestations associated with DN, including reductions in fasting blood glucose levels, 24-hour urine output, renal indices, amelioration of glomerular histopathological abnormalities, diminished glycogen accumulation, and fibrosis. Furthermore, DN-afflicted renal tissues exhibited decreased MDA levels and elevated expression of AMPK/Nrf2 pathway-associated proteins. The beneficial effects of GSTD on DN and its protein modulation were reversed upon co-intervention with compound C. Together, our findings imply that GSTD improves DN by activating the AMPK/Nrf2 pathway, thereby mitigating STZ-induced renal damage, inflammatory responses, and oxidative stress.

Impact of remimazolam on postoperative inflammatory markers and complications in thoracoscopic pulmonary lobectomy patients: A retrospective analysis.

Remazolam is widely used for procedural sedation in intensive care units. It has been shown to have anti-inflammatory and organ-protecting properties. However, the changes in inflammatory markers and analgesic effects of remazolam after thoracoscopic pulmonary lobectomy remain unclear. This study aims to assess the effects of the novel drug remimazolam on inflammatory factor levels and postoperative complications in thoracoscopic pulmonary lobectomy patients, providing a scientific basis for clinical use. This retrospective study analyzed 200 thoracoscopic pulmonary lobectomy patients, who were divided into a control group and a remimazolam group based on their anesthesia method. Patients in ramazolam group were anesthetized with ramazolam, while patients in control group were anesthetized with propofol. All patients were performed by the same physician team and anesthesia team. Inflammatory factors (including interleukin-6 [IL-6], C-reactive protein [CRP], including interleukin-8) were measured preoperatively and postoperatively, and postoperative complication rates were compared between the 2 groups. The levels of IL-6 and CRP were significantly higher in the remimazolam group at 7 days postoperatively compared to the control group. No significant differences were observed in preoperative inflammatory factors or postoperative including interleukin-8 levels between the 2 groups. Additionally, there were no significant differences in the overall incidence of postoperative complications or in specific complications such as pulmonary infection, atelectasis, subcutaneous emphysema, pneumothorax, surgical site infection, and arrhythmia. Patients receiving remimazolam had higher postoperative IL-6 and CRP levels compared to the control group, without an increase in postoperative complications. In clinical use, attention should be paid to the control of inflammatory indicators in patients using remazolam. However, due to potential confounding factors and the retrospective design, we cannot establish a causal relationship between remimazolam and elevated inflammatory markers. These findings suggest a possible association that requires cautious interpretation. Further research is needed to assess the clinical relevance and explore the underlying mechanisms.

The Expression Level of Inflammation-Related Genes in Patients With Bone Nonunion and the Effect of BMP-2 Infected Mesenchymal Stem Cells Combined With nHA/PA66 on the Inflammation Level of Femoral Bone Nonunion Rats

Bone nonunion delays fracture end repair and is associated with inflammation. Although bone nonunion can be effectively repaired in clinical practice, many cases of failure. Studies have confirmed that BMP-2 and nHA/PA66 repaired bone defects successfully. There are few studies on the effects of the combined application of BMP-2 and NHA/PA66 on bone nonunion osteogenesis and inflammation. We aimed to investigate the expression level of inflammation-related genes in patients with bone nonunion and the effect of BMP-2-infected mesenchymal stem cells combined with nHA/PA66 on the level of inflammation in femur nonunion rats. We searched for a gene expression profile related to bone nonunion inflammation (GSE93138) in the GEO public database. Bone marrow mesenchymal stem cells (MSCs) of SD rats were cultured and passed through. We infected the third generation of MSCs with lentivirus carrying BMP-2 and induced the infected MSCs to bone orientation. We detected the expression level of BMP-2 by RT-PCR and the cell viability and alkaline phosphatase (ALP) activity by CCK8 and then analyzed the cell adhesion ability. Finally, the levels of related inflammatory factors, including C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and Erythrocyte Sedimentation Rate (ESR), were detected in nonunion rats. Our findings: The patients with nonunion had up-regulated expression of 26 differentially inflammatory genes. These genes are mainly enriched in innate immune response, extracellular region, calcium ion binding, Pantothenate and CoA biosynthesis pathways. The expression level of BMP-2 in the Lenti-BMP-2 group was higher (vs. empty lentivirus vector group: t=5.699; vs. uninfected group t=3.996). The cell activity of the MSCs + BMP-2 + nHA/PA66 group increased gradually. After being combined with nHA/PA66, MSCs transfected with BMP-2 spread all over the surface of nHA/PA66 and grew into the material pores. MSCs + BMP-2 + nHA/PA66 cells showed positive ALP staining, and the OD value of ALP was the highest. The levels of CRP, IL-6, TNF-α, and ESR in the MSCs + BMP-2 + nHA/PA66 group were lower than those in the MSCs and MSCs + nHA/PA66 group but higher than those in MSCs + BMP-2 group. The above comparisons were all P˂0.05. The findings demonstrated that the expression level of inflammation-related genes increased in the patients with bone nonunion. The infection of MSCs by BMP-2 could promote the directed differentiation of MSCs into osteoblasts in the bone marrow of rats, enhance the cell adhesion ability and ALP activity, and reduce inflammation in rats with bone nonunion.

Fucoidan improves intestinal peristaltic function in rats with postoperative ileus.

The effect of fucoidan on postoperative ileus (POI) has not been studied. In this study, how fucoidan ameliorates POI in a rat POI model was investigated. The results showed that in the model animals, when the first defecation time was prolonged, the amount of food consumed decreased, the small intestinal propulsion rate dramatically slowed, and the motility index (MI%) of the small intestine decreased. In vitro experiments revealed that the contractile response of small intestinal smooth muscle strips to carbachol (CCh) was reduced. Immunohistochemistry revealed evident macrophage infiltration in the intestinal muscularis. However, after oral pretreatment with fucoidan, the time to first defecation decreased, and food intake, the small intestinal propulsion rate, and MI% of the small intestine increased. Additionally, the contractile response of the intestinal strips to CCh became stronger, and macrophage infiltration decreased. Mechanistically, fucoidan alleviated POI by exerting anti-inflammatory and antioxidant effects as well as likely through the TrkB/ERK1/2/Akt signalling pathways. When POI occurred, the expression levels of inflammatory factors in the intestines significantly increased while the phosphorylation of TrkB, ERK1/2, and Akt significantly decreased; malondialdehyde (MDA) levels in the intestines increased but the levels of superoxide dismutase (SOD) and glutathione (GSH) decreased. In contrast, after pretreatment with fucoidan, the expression levels of inflammatory factors decreased; the phosphorylation levels of TrkB, ERK1/2, and Akt increased; the MDA level decreased; and SOD and GSH levels increased. Thus, fucoidan alleviated POI-induced impairment of rat intestinal motility through anti-inflammatory and antioxidant effects possibly associated with the TrkB/ERK1/2 and Akt signalling pathways.

The levels and clinical significance of serum miR-146a, miR-145, Th17/Treg in children with respiratory syncytial virus infection pneumonia

To investigate the levels and clinical significance of serum microRNA (miR)-146a, miR-145, T-helpertype17 (Th17)/regulatory T cell (Treg) in children with respiratory syncytial virus (RSV) infectious pneumonia. The clinical data of 200 children with RSV infectious pneumonia admitted to Nantong Maternal and Child Health Hospital from June 2020 to June 2023 were retrospectively collected as the study group. At the same time, 200 children with mycoplasma pneumonia were selected as the common pneumonia group and 200 healthy children were selected as the healthy group. The levels of serum inflammatory factors [interleukin-6 (IL-6), interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α)] were detected by enzyme-linked immunosorbent assay. The expression levels of serum miR-146a and miR-145 were detected by RT-qPCR. The levels of Th17/Treg were detected by flow cytometry. The levels of miR-146a, miR-145, Th17/Treg and serum inflammatory factors were compared among the three groups. Pearson method was used to analyze the correlation between miR-146a, miR-145, Th17/Treg and serum inflammatory factors in children with RSV infectious pneumonia. The receiver operating characteristic (ROC) curve was drawn to analyze the diagnostic value of miR-146a, miR-145, Th17/Treg in children with respiratory syncytial virus infection pneumonia. The results showed that in the study group, miR-146a (2.01±0.58), miR-145 (1.81±0.46), Th17/Treg (1.09±0.31), IL-6 (7.82±2.11) ng/L and TNF-α (9.82±2.96) ng/L were higher than those in the common pneumonia group miR-146a (1.49±0.42), miR-145 (1.43±0.31), Th17/Treg (0.77±0.24), IL-6 (5.89±1.32) ng/L, TNF-α (7.34±2.32) ng/L and healthy group miR-146a (1.25±0.19), miR-145 (1.19±0.16), Th17/Treg (0.38±0.09), IL-6 (4.52±1.04) ng/L, TNF-α (5.39±1.07)ng/L. The levels of the above indexes in the common pneumonia group were higher than those in the healthy group, and the differences were statistically significant (F=183.543, 175.938, 617.182, 226.657, 193.459, P<0.05). In the study group, IFN-γ (14.18±3.25) pg/ml was lower than that in the control group (19.52±5.13) pg/ml, but higher than that in the healthy group (9.77±2.40) pg/ml, and the difference was statistically significant (F=335.432, P<0.05). Pearson correlation analysis showed that miR-146a, miR-145 and Th17/Treg were positively correlated with IL-6 and TNF-α (P<0.05), but negatively correlated with IFN-γ (P<0.05). ROC curve results showed that the area under the curve (AUC) of miR-146a, miR-145 and Th17/Treg in the diagnosis of RSV infectious pneumonia was 0.767, 0.762 and 0.790, respectively, while the combined detection of the three was 0.904. In conclusion, the levels of miR-146a, miR-145 and Th17/Treg are highly expressed in children with RSV infectious pneumonia, and are closely related to the inflammatory response of children. The combined detection of the three may have certain application value in the auxiliary diagnosis of RSV infectious pneumonia.

Integrated gut microbiome and UHPLC-MS metabolomics to reveal the prevention mechanism of pidanjiangtang granules on IGT Rats

IntroductionPidanjiangtang (PDJT) is a traditional Chinese medicine formula empirically used to treat impaired glucose tolerance (IGT) based on the "Pidan" theory from the classic ancient book Nei Jing. However, the mechanism of PDJT intervention for IGT remains to be studied. ObjectiveThis study aims to explore the mechanism of PDJT granules intervention in IGT by integrating gut microbiome and UHPLC-MS untargeted metabolomics. Materials and methodsThe IGT model was established in 6-week-old male Sprague-Dawley (SD) rats by feeding them a high-fat diet and using an STZ injection. The low, medium, and high doses of PDJT were used for six weeks. metformin (Glucophage) was used as the positive control drug. The efficacy of PDJT was evaluated using fasting blood glucose (FBG), blood glucose maximum (BGmax), blood lipid, and inflammatory factor levels. Finally, 16S rDNA gut microbiome sequencing with metabolomics analysis was used to explore the pharmacological mechanism of PDJT intervention in IGT. ResultsPDJT could reverse the phenotype of IGT rats, reduce blood glucose levels, improve lipid metabolism disorder, and reduce inflammatory response. Gut microbiome analysis found that PDJT can improve gut microbiota composition and abundance of three phyla (Firmicutes, Bacteroidota, Desulfobacterota) and four genera (unclassified_f__Lachnospiraceae, Ruminococcus, Allobaculum, Desulfovibrio), which play an important role in the process of PDJT intervention on glucose metabolism and lipid metabolism in IGT rats. UHPLC-MS untargeted metabolomics showed that PDJT could regulate the levels of 258 metabolites in lipid metabolism pathways, inflammatory response pathways, fat and protein digestion, and absorption. The combined analysis of the two omics showed that improving the body's metabolism by gut microbes may be the possible mechanism of PDJT in treating IGT. Thus, this study provides a new method to integrate gut microbiome and UHPLC-MS untargeted metabolomics to evaluate the pharmacodynamics and mechanism of PDJT intervention in IGT, providing valuable ideas and insights for future research on the treatment of IGT with traditional Chinese medicine.

Flavonoids attenuate inflammation of HGF and HBMSC while modulating the osteogenic differentiation based on microfluidic chip

BackgroundWhen inflammation occurs in periodontal tissues, a dynamic cellular crosstalk interacts between gingival fibroblasts and bone marrow mesenchymal stem cells (BMSCs), which plays a crucial role in the biological behaviour and differentiation of the cells. Recently, flavonoids are increasingly recognized for their therapeutic potential in modulating inflammation and osteogenic differentiation. Owing to their varied molecular structures and mechanisms, there are more needs that flavonoid compounds should be identified by extensive screening. However, current drug research mostly relies on static, single-type cell cultures. In this study, an innovative bionic microfluidic chip system tailored for both soft and hard tissues was developed to screen for flavonoids suitable for treating periodontitis.MethodsThis study developed a microfluidic system that bionically simulates the soft and hard structures of periodontal tissues. Live/dead staining, reactive oxygen species (ROS) staining, and RT-qPCR analysis were employed. These techniques evaluated the effects of flavonoid compounds on the levels of inflammatory factors and ROS contents in HGF and HBMSC under LPS stimulation. Additionally, the impact of these compounds on osteogenic induction in HBMSC and the exploration of the underlying mechanisms were assessed.ResultsThe microfluidic chip used in this study features dual chambers separated by a porous membrane, allowing cellular signal communication via bioactive factors secreted by cells in both layers under perfusion. The inflammatory response within the chip under LPS stimulation was lower compared to individual static cultures of HGF and HBMSC. The selected flavonoids-myricetin, catechin, and quercetin-significantly reduced cellular inflammation, decreased ROS levels, and enhanced osteogenic differentiation of BMSCs. Additionally, fisetin, silybin, and icariside II also demonstrated favorable outcomes in reducing inflammation, lowering ROS levels, and promoting osteogenic differentiation through the Wnt/β-catenin pathway.ConclusionsThe bionic microfluidic chip system provides enhanced capabilities for drug screening and evaluation, delivering a more precise assessment of drug efficacy and safety compared to traditional in vitro methods. This study demonstrates the efficacy of flavonoids in influencing osteogenic processes in BMSCs primarily through the Wnt/β-catenin pathway. These results uncover the potential of flavonoids as therapeutic medicine for treating periodontitis, meriting further research and development.Graphical

Mediation effect of peripheral blood inflammatory factors in the association between severity of nonlactating mastitis and glycemic abnormalities

Background: The association between severity of non-lactating mastitis and glycemic abnormalities was analyzed to investigate the mediating role of peripheral inflammatory factor levels in the association. Methods: A total of 337 cases were included in this study, including 195 cases in the control group and 142 cases in the case group. Multifactorial logistic regression was used to analyze the associations between the severity of NLM and glycemic abnormality and peripheral inflammatory factors, and a mediation model was used to explore the mediating roles of the levels of hs-CRP, WBC, and IL-6 in the associations between the two. Results: The inflammatory factors IL-6, WBC, and hs-CRP had mediating effects, with effect values of 0.009 (0.003-0.038), 0.006(0.001-0.047), and 0.007(0.001-0.051), and mediating effect percentages of 2.38%, 2.12%, and 2.24%, respectively. Conclusion: NLM severity and glycemic abnormalities were positively correlated with peripheral inflammatory factors, and peripheral inflammatory factors played a partial mediating role in the association.

Salidroside attenuates sepsis-induced acute lung injury by inhibiting ferroptosis-dependent pathway.

Sepsis triggers a systemic inflammatory response that can lead to acute lung injury (ALI). Salidroside (SAL) has many pharmacological activities such as antiinflammatory and anti-oxidation. The objective of the study was to explore the mechanism of SAL on ALI caused by sepsis. A model of ALI in septic mice was established by cecal ligation and puncture. Following SAL treatment, the effect of SAL on the ferroptosis pathway in mice was analyzed. The pathological damage of lung tissue, the levels of inflammatory factors and apoptosis in bronchoalveolar lavage fluid (BALF) of mice were evaluated, and the changes of gene expression level and metabolite content abundance were explored by combining transcriptomics and metabolomics analysis. The effect of SAL on ferroptosis in mice with lung injury was observed by intraperitoneal injection of ferroptosis activator Erastin or ferroptosis inhibitor Ferrostatin-1 to promote or inhibit ferroptosis in mice. SAL significantly alleviated the pathological damage of lung tissue, decreased the number of TUNEL positive cells and the levels of TNF-α, IL-1β, IL-6 in BALF, and increased the level of IL- 10 in lung injury mice. Moreover, the Fe2+ content and malondialdehyde decreased significantly, the reactive oxygen species and glutathione content increased significantly, and the arachidonic acid metabolites 20-hydroxyeicosatetraenoic acid (20- HETE), (5Z, 8Z, 10E, 14Z)-12-Oxoeicosa-5,8,10,14-tetraenoic acid (12-OxOETE), (5Z, 8Z, 10E, 14Z)-(12S)-12-Hydroxyeicosa-5,8,10,14-tetraenoic acid (12(S)-HETE), (5Z, 8Z, 14Z)-11,12-Dihydroxyeicosa-5,8,14-trienoic acid (11,12-DHET), (5Z, 11Z, 14Z)-8,9- Dihydroxyeicosa-5,11,14-trienoic acid, Leukotriene B4, Leukotriene D4 were significantly up-regulated after SAL treatment. Salidroside alleviates ALI caused by sepsis by inhibiting ferroptosis.

KLF2 Inhibits Ferroptosis and Improves Mitochondrial Dysfunction in Chondrocyte Through SIRT1/GPX4 Signaling to Improve Osteoarthritis.

Osteoarthritis (OA), a disease of articular joints, is the leading cause of disability in the elderly. Repressing ferroptosis and improving mitochondrial function can delay the progression of OA. Kruppel-like factor 2 (KLF2) exerts a protective effect on OA. However, whether KLF2 affects ferroptosis and mitochondrial function during OA remains unknown. The OA in vivo and in vitro models were constructed in this work. The structural damage of knee joint in OA mice was evaluated through Micro-CT scanning. H&E, SOFG, TB, and TUNEL staining were applied for pathological examination of cartilage tissues. ELISA was employed to examine the contents of inflammatory factors. Additionally, iron deposition in cartilage tissues was measured by Prussian blue staining, and the levels of proteins related to ferroptosis were assessed by immunoblotting. Besides, mitochondrial morphology and function were estimated using a transmission electron microscope and JC-1 staining. In interleukin (IL)-1β-treated C28/I2 cells, the levels of inflammatory factors, intracellular ROS, mitochondrial ROS, lipid ROS, and Fe2+ were measured. Mitochondrial function was evaluated by detecting the levels of mitochondrial membrane potential (MMP), ATP, mPTP, and OCR. KLF2 overexpression ameliorated the structural damage of knee cartilage in OA mice. KLF2 upregulation inhibited ferroptosis and alleviated mitochondrial damage in knee cartilage of OA mice and IL-1β-treated C28/I2 cells. Moreover, KLF2 overexpression activated SIRT1/GPX4 signaling in vivo and in vitro. EX527 addition blocked the influences of KLF2 upregulation on ferroptosis and mitochondrial dysfunction in IL-1β-treated C28/I2 cells. Altogether KLF2 inhibits ferroptosis and improves mitochondrial dysfunction in chondrocytes through SIRT1/GPX4 signaling to improve OA.

Clinical Significance of Combined Detection of CCL22 and IL-1 as Potential New Bronchial Inflammatory Mediators in Children's Asthma.

Severe asthma is a significant health burden because children with severe asthma are vulnerable to medication-related side effects, life-threatening deterioration, and impaired quality of life. However, there is a lack of data to elucidate the role of inflammatory variables in asthma. This study aimed to compare the levels of inflammatory factors in serum and sputum in children with acute and stable asthma to those in healthy children and the ability to predict clinical response to azithromycin therapy. This study recruited 95 individuals aged 1-3 years old and collected data from January 2018 to 2020. We examined serum and sputum inflammatory factors and constructed the least absolute shrinkage and selection operator (LASSO) model. Predictive models were constructed through multifactor logistic regression and presented in the form of column-line plots. The performance of the column-line diagrams was measured by subject work characteristics (ROC) curves, calibration plots, and decision curve analysis (DCA). Then, filter-paper samples were collected from 45 children with acute asthma who were randomly assigned to receive either azithromycin (10 mg/kg, n = 22) or placebo (n = 23). Pretreatment levels of immune mediators were then analyzed and compared with clinical response to azithromycin therapy. Of the 95 eligible participants, 21 (22.11%) were healthy controls, 29 (30.53%) had stable asthma, and 45 (47.37%) had acute asthma. The levels of interferon-γ (IFN-γ), tumor necrosis factor-a (TNF-α), chemokine CCL22 (CCL22), interleukin 12 (IL-12), chemokine CCL4 (CCL4), chemokine CCL2 (CCL2), and chemokine CCL13 (CCL13）were significantly higher in the acute asthma group than in the stable asthma group. A logistic regression analysis was performed using CCL22 and IL-1 as independent variables. Additionally, IFN-γ, TNF-α, IL-1, IL-13, and CCL22 were identified in the LASSO model. Finally, we found that CCL22 and IL-1 were more responsive in predicting the response to azithromycin treatment. Our results show that CCL22 and IL-1 are both representative markers during asthma symptom exacerbations and an immune mediator that can predict response to azithromycin therapy.

Fructus Arctii Mitigates Depressive Disorder via the Let-7e-Modulated Toll-Like Receptor (TLR) Signaling Pathway.

Depressive disorder is a common and serious public health challenge globally. Fructus arctii is a traditional medicinal plant ingredient with diverse pharmacological effects. This study aimed to investigate the therapeutic potential of Fructus arctii in alleviating depressive-like behaviors. We established a chronic unpredictable mild stress (CUMS)-induced depression mouse model to assess the antidepressant effects of Fructus arctii. BV2 cells treated with lipopolysaccharide (LPS) were used to mimic neuronal damage. Behavioral tests, including the sucrose preference test, tail-suspension test, and forced swim test, were conducted to evaluate the impact of Fructus arctii on depressive-like behaviors. Let-7e expression was detected by RT-qPCR, and TLR4 signaling pathway activation was evaluated by western blot analysis, which also assessed the inflammatory response by measuring levels of IL-6, IL-1β, MCP-1, TNF-α, and iNOS. Immunohistological analysis was conducted to detect the expression of microglia markers. Luciferase reporter assays verified the interaction between let-7e and TLR4. Fructus arctii administration effectively alleviated depressive-like behaviors induced by CUMS in mice, as evidenced by improved sucrose preference and reduced immobility time in behavioral tests. Mechanistically, Fructus arctii reversed the CUMS-induced downregulation of let-7e and upregulation of TLR4 and MyD88 protein levels in mice hippocampus tissues. In addition, Fructus arctii suppressed microglial activation and reduced the levels of inflammatory factors by upregulating let-7e. Let-7e was verified to bind to TLR4, thereby negatively regulating its expression. TLR4 overexpression reversed the suppressive effect of let-7e upregulation on inflammatory reactions and microglial activation. Furthermore, intracerebroventricular injection of let-7e agomiR alleviated depressive-like behavior and inhibited microglial activation in vivo. In summary, Fructus arctii mitigates depression by regulating the let-7e/TLR4/MyD88 pathway, offering new insights into potential depression therapies.

PM2.5 Promotes Macrophage-Mediated Inflammatory Response Through Airway Epithelial Cell-Derived Exosomal miR-155-5p.

Airway epithelial cells (AECs) and alveolar macrophages are involved in airway inflammation. The direct effects of atmospheric fine-particulate-matter (PM2.5) on airway cells, such as AECs and alveolar macrophages, have been widely investigated, but the effect of cell-cell interaction on inflammatory response remains unclear. Exosomes play a crucial role in intercellular communication. However, the cellular interaction of exosomes in PM2.5-induced airway inflammation is unclear. The PM2.5-induced human bronchial epithelial (BEAS-2B) cells and phorbol 12-myristate 13-acetate-induced macrophages (Mφ) were co-cultured and then the expression of IL-6, IL-1β, TNF-α and miRNA-155-5p were detected. Exosomes from PM2.5-exposed BEAS-2B cells were then co-cultured with Mφ to detect the expression of miR-155-5p and inflammatory cytokines, as well as cytokine signaling inhibitor-1 (SOCS1)/NFκB, and to detect the effect of the exosome inhibitor GW4869. After the co-culture of PM2.5-induced BEAS-2B cells and Mφ, the expression of Mφ-derived IL-6, IL-1β, and TNF-α, as well as miRNA-155-5p were upregulated. The expression of miRNA-155-5p was upregulated in BEAS-2B and BEAS-2B cell-derived exosomes after exposure to PM2.5. Furthermore, co-culturing exosomes derived from PM2.5-exposed BEAS-2B cells with Mφ, upregulated miR-155-5p and inflammatory cytokines, decreased cytokine signaling inhibitor-1 (SOCS1) expression, and activated NF-κB. In addition, adding exosome inhibitor GW4869 to PM2.5-interfered BEAS-2B cells co-culture with Mφ downregulated miRNA-155-5p expression, inhibited NF-κB, and reduced the levels of inflammatory factors. PM2.5 promotes Mφ inflammation by upregulating miRNA-155-5P in exosomes obtained from BEAS-2B cells through miR-155-5P/SOCS1/NF-κB pathway. Exosomal miRNAs mediate cellular communication between BEAS-2B cells and Mφ, which may be a new mechanism of PM2.5-stimulated pulmonary inflammatory response.