[Knockdown of IL-33 suppresses the expression of inflammatory factors and NLRP3 to inhibit the inflammatory response in asthmatic mice].

Objective To explore the regulatory mechanism of interleukin-33 (IL-33) on the inflammatory response in asthmatic mice. Methods Using 10 µg/mL of lipopolysaccharide (LPS) to establish a cellular inflammation model of mouse bone marrow mesenchymal stem cells (BMMSCs), the cells were divided into three groups: small interfering RNA of IL-33(si-IL-33) group, IL-33 overexpression (IL-33-OE) group, and model group, based on the transfection status of si-IL-33 plasmid and IL-33-OE plasmid. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to detect mRNA expression of IL-33, nucleotide binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3), IL-1ß and IL-6. Fluo-3 AM was used to measure calcium ion content, and JC-1 mitochondrial membrane potential detection kit was performed to detect mitochondrial membrane potential changes. An asthma mouse model was established by intraperitoneal injection of sensitizers and activators. According to different treatment plans, the asthmatic mice were divided into si-IL-33 group, IL-33-OE group and model group, with 5 mice in each group. ELISA was used to detect the levels of IL-1ß, IL-6 and NLRP3 in mouse serum, while HE staining and Masson staining were performed to assess lung tissue lesions. Results Compared with the model group, the mRNA expression levels of IL-33, NLRP3, IL-1ß and IL-6 in the si-IL-33 group were all reduced, while those in the IL-33-OE group were increased. The calcium ion fluorescence was decreased in BMMSCs, while it was increased in the IL-33-OE group. In the si-IL-33 group, JC-1 existed in a polymer form in mitochondria, showing bright red fluorescence and weak green fluorescence, indicating stable mitochondria and normal mitochondrial function. After treating with IL-33-OE plasmid to reduce the mitochondrial membrane potentia, JC-1 cannot exist in polymer form within the mitochondrial matrix. At this point, the red fluorescence intensity inside the mitochondria decreases significantly, while the green fluorescence in the cytoplasm increases significantly. The levels of IL-1ß, IL-6, and NLRP3 in the serum of mice in the si-IL-33 group were significantly lower, while those in the IL-33-OE group were significantly higher. In the si-IL-33 group, almost no inflammatory cell infiltration was observed, indicating a relief of inflammation and normal epithelial cell morphology. Additionally, the fibrotic portion of the lung tissue in the si-IL-33 group tended to be normal. The total wall area of bronchus (WAt)/basement membrane perimeter (Pbm) and wall area of bronchial smooth muscle (WAm)/Pbm were reduced in the si-IL-33 group compared with the model group, while they were increased in the IL-33-OE group. Conclusion Knockdown of IL-33 inhibits the inflammatory response in asthmatic mice by downregulating the expression of NLRP3, IL-1ß and IL-6.

Efficacy and inflammatory levels (IL-6, IL-10) of adjuvant application of vitamin-A in the treatment of pediatric Mycoplasma pneumoniae pneumonia: a systematic review and meta-analysis.

Objective: The purpose of this study is to evaluate the efficacy of Vitamin A (VitA) as an adjuvant therapy for pediatric Mycoplasma Pneumoniae Pneumonia (MPP) through meta-analysis, and to investigate its impact on inflammation levels (IL-6, IL-10), in order to explore the role of VitA in pediatric MPP. Methods: Using a systematic literature search method, relevant research literature is searched, and RCT studies that meet the requirements are selected based on preset inclusion and exclusion criteria. Then, a quality evaluation was conducted on the included literature, and meta-analysis was used to calculate the combined effect values of mortality rate, hospital stay, lung rale disappearance time, cough duration, fever duration, IL-6 and IL-10 levels, and heterogeneity analysis was conducted. The levels of IL-6 and IL-10 represent the inflammatory levels in pediatric MPP patients, and exploring their changes has significant implications for the anti-inflammatory effect of treatment. Results: A total of 10 RCT studies were included, with a total sample size of 1,485, including 750 cases in the control group and 735 cases in the observation group. The meta-analysis results of this study showed that there was a significant difference in the total clinical efficacy of using VitA adjuvant therapy compared to the control group without VitA [OR = 3.07, 95%CI = (2.81, 4.27)], P < 0.05. However, there was no significant difference in the adverse reaction rate between the use of VitA as an adjuvant therapy and the control without VitA [OR = 1.17, 95%CI = (0.61, 2.27)], P > 0.05. At the same time, the hospitalization time [MSD = -0.86, 95% CI = (-1.61, -0.21)], lung rale disappearance time [MSD = -0.78, 95%CI = (-1.19,-0.51)], cough duration [MSD = -1.07, 95%CI = (-1.41, -0.71)], and fever duration [MSD = -0.47, 95%CI = (-0.72, -0.23)] using VitA as an adjuvant treatment were obviously lower. In addition, the meta-analysis outcomes also showed that the use of VitA adjuvant therapy can significantly reduce IL-6 [MSD = -1.07, 95%CI = (-1.81, -0.27)] and IL-10 [MSD = -0.13, 95%CI = (-0.31, 0.12)] levels. This indicates that the application of VitA in pediatric MPP also has the effect of reducing inflammatory response. Conclusion: Based on the meta-analysis results, VitA adjuvant therapy can significantly improve the clinical symptoms of pediatric MPP patients, shorten hospitalization time, promote the disappearance of lung rales, and alleviate cough and fever symptoms. In addition, VitA adjuvant therapy can effectively reduce inflammation levels, indicating its potential role in inhibiting inflammatory responses. In clinical practice, VitA adjuvant therapy for pediatric MPP can be promoted as a potential treatment option.

Nanotechnology boosts the efficiency of tumor diagnosis and therapy.

The incidence and mortality of cancer are gradually increasing. The highly invasive and metastasis of tumor cells increase the difficulty of diagnosis and treatment, so people pay more and more attention to the diagnosis and treatment of cancer. Conventional treatment methods, including surgery, radiotherapy and chemotherapy, are difficult to eliminate tumor cells completely. And the emergence of nanotechnology has boosted the efficiency of tumor diagnosis and therapy. Herein, the research progress of nanotechnology used for tumor diagnosis and treatment is reviewed, and the emerging detection technology and the application of nanodrugs in clinic are summarized and prospected. The first part refers to the application of different nanomaterials for imaging in vivo and detection in vitro, which includes magnetic resonance imaging, fluorescence imaging, photoacoustic imaging and biomarker detection. The distinctive physical and chemical advantages of nanomaterials can improve the detection sensitivity and accuracy to achieve tumor detection in early stage. The second part is about the nanodrug used in clinic for tumor treatment. Nanomaterials have been widely used as drug carriers, including the albumin paclitaxel, liposome drugs, mRNA-LNP, protein nanocages, micelles, membrane nanocomplexes, microspheres et al., which could improve the drug accumulate in tumor tissue through enhanced permeability and retention effect to kill tumor cells with high efficiency. But there are still some challenges to revolutionize traditional tumor diagnosis and anti-drug resistance based on nanotechnology.

Identification of a Novel ACTN4 Gene Mutation Which Is Resistant to Primary Nephrotic Syndrome Therapy.

ACTN4, a gene which codes for the protein α-actinin-4, is critical for the maintenance of the renal filtration barrier. It is well known that ACTN4 mutations can lead to kidney dysfunction, such as familial focal segmental glomerulosclerosis (FSGS), a common cause of primary nephrotic syndrome (PNS). To elucidate whether other mutations of ACTN4 exist in PNS patients, we sequenced the ACTN4 gene in biopsies collected from 155 young PNS patients (≤16 years old). The patients were classified into five groups: FSGS, minimal change nephropathy, IgA nephropathy, membranous nephropathy, and those without renal puncture. Ninety-eight healthy people served as controls. Samples were subjected to Illumina's next generation sequencing protocols using FastTarget target gene capture method. We identified 5 ACTN4 mutations which occurred only in PNS patients: c.1516G > A (p.G506S) on exon 13 identified in two PNS patients, one with minimal change nephropathy and another without renal puncture; c.1442 + 10G > A at the splice site in a minimal change nephropathy patient; c.2191-4G > A at the cleavage site, identified from two FSGS patients; and c.1649A > G (p.D550G) on exon 14 together with c.2191-4G > A at the cleavage sites, identified from two FSGS patients. Among these, c.1649A > G (p.D550G) is a novel ACTN4 mutation. Patients bearing the last two mutations exhibited resistance to clinical therapies.

The association of RAR-related orphan receptor A (RORA) gene polymorphisms with the risk of asthma.

Asthma is a common, heterogeneous chronic respiratory disease characterized by chronic inflammation of the airway, airway hyperreactivity, and airway remodeling. The RAR-related orphan receptor A (RORA) gene has been identified for the pathogenesis of asthma. The purpose of this research was to investigate the relationship between RORA gene polymorphisms and asthma susceptibility in the Chinese Zhuang population. This was a case-control study including 231 children with asthma and 343 healthy controls. The RORA gene polymorphisms were measured by the polymerase chain reaction-ligase detection reaction genotyping assays and confirmed by sequencing. The distribution of the genotype frequencies of the RORA rs11071559 C>T was significantly different in the group of cases and the healthy children (P < 0.05). By haplotype analyses, the haplotype TT (rs7164773/rs11071559) was statistically significant between asthmatics and nonasthmatics, but the association was not significant after correction for multiple comparisons. Our results provided evidence that the RORA rs11071559C>T polymorphism was associated with an elevated susceptibility to pediatric asthma in the Chinese Zhuang population.