Therapeutic Potential and Mechanisms of Mesenchymal Stem Cell and Mesenchymal Stem Cell-Derived Extracellular Vesicles in Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic and inflammatory skin disease with intense itchiness that is highly prevalent worldwide.The pathogenesis of AD is complex and closely related to genetic factors, immunopathogenic factors, environmental factors, and skin infections. Mesenchymal stem cells (MSCs) are non-hematopoietic progenitor cells derived from the mesenchymal stroma. They have anti-inflammatory, anti-apoptotic, and regenerative properties. Numerous studies demonstrate that MSCs can play a therapeutic role in AD by regulating various immune cells, maintaining immune homeostasis, and promoting the repair of damaged tissues. The key mediators for their biological functions are extracellular vesicles (MSC-Evs) and soluble cytokines derived from MSCs. The safety and efficacy of MSCs have been demonstrated in clinical Phase I / IIa trials for AD. This paper provides a comprehensive review of the pathogenesis of AD and the currently published studies on the function of MSCs and MSC-Evs in AD, primarily including the pathogenesis and the immunomodulatory impacts of MSCs and MSC-Evs, along with advancements in clinical studies. It provides insights for comprehending AD pathogenesis and investigating treatments based on MSCs.

A single center retrospective study of systemic reactions' distribution and risk factors to subcutaneous immunotherapy with dust mite extract in patients with allergic rhinitis and/ or asthma.

To analyze various risk factors including causes that may lead to adverse reactions, especially systemic adverse reactions（SRs）, before and after mite allergen subcutaneous immunotherapy (SCIT), so as to provide real-world reference data for further improving the safety of mite allergen SCIT. Methods: The local adverse reactions（LRs）and SRs of 230 patients with allergic rhinitis and/or asthma who received SCIT in Weifang people's hospital were analyzed retrospectively. The data of patient characteristics, drug factors and environmental elements of adverse reactions were collected and statistically analyzed. Results: There were 28 cases (12.2%) of SRs in 230 patients. All the patients received a total of 7515 injections and 37 SRs (0.49%) were observed. 32.4% (12/37) of SRs could identify their external and subjective triggers. SRs patients had higher 2-year SCIT compliance than no-SRs patients (p = 0.026). The prevalence of SRs in SCIT patients with atopic dermatitis or simple allergic asthma are no statistical significance (P = 0.111). Conclusion: the incidence of SRs in this study is within an ideal range. Through professional patient education and pre injection risk factor assessment, Compliance is still well-controlled and guaranteed although SRs occurred.

The Specific microRNA Profile and Functional Networks for Children with Allergic Asthma.

Background: Allergic asthma is the most common type of asthma and often occurs in early life with increasing comorbidities, including atopic dermatitis and allergic rhinitis. MicroRNAs (miRNAs) are involved in the pathogenesis of numerous immune and inflammatory disorders, particularly allergic inflammation. The specific miRNA profiles of children with allergic asthma have not been fully delineated and still require in-depth study. Objective: This study aimed to identify the expression profile of miRNAs and constructed a network of the interactions between differentially expressed miRNAs and target mRNAs to provide novel insights into understanding the pathogenesis of allergic asthma. Materials and Methods: In this study, we performed high-throughput sequencing of peripheral blood mononuclear cells (PBMCs) from children in the acute phase of asthma. Bioinformatics approaches, including miRanda, Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, were employed to predict novel therapeutic and diagnostic targets for allergic asthma. Real-time quantitative PCR was conducted to detect the expression of aberrantly expressed miRNAs. Results: One hundred and sixty-one differentially expressed miRNAs were identified in children with allergic asthma, including 140 conserved miRNAs and 21 novel miRNAs. A total of 8929 targeted mRNAs (44,186 transcripts) associated with differentially expressed miRNAs were predicted and significantly enriched in the cGMP-PKG signalling pathway, cholinergic synapse, and salivary secretion. We also found that miRNA-370-3p targeted PKG and MLCP molecules in the cGMP-PKG signalling pathway and was involved in the pathogenesis of allergic asthma. Conclusion: We identified the miRNA profile of PBMCs in children with allergic asthma and also found that miRNA-370-3p targeted PKG and MLCP molecules in the cGMP-PKG signalling pathway, which provides a novel insight into understanding the pathogenesis of allergic asthma and investigating new targets for the treatment of allergic asthma in children.

Prediction model for different progressions of Atherosclerosis in ApoE-/- mice based on lipidomics.

Atherosclerosis (AS) is a progressive disease with a complex pathogenesis which is characterized by dyslipidemia and changes in the vascular wall composition. According to the degree of lesions, atherosclerosis can be divided into four stages: hyperlipidemia, lipid stria, fiber plaque, and atherosclerotic plaque. The present study aimed to establish a prediction model for the different pathological stages of AS based on lipidomics. ApoE-/- mice and C57BL/6 mice fed a normal diet were divided into seven groups according to the feeding time (8, 12, 16, 20, 24, 28, and 32 weeks). The changes in the lipid composition and serum content were detected using ultra-performance liquid chromatography coupled with quadrupole time-of-flight high-definition mass spectrometry (UPLC-Q-TOF/MS). Through the results of serum total cholesterol, triglyceridelow density lipoprotein at each time and HE staining of the head and arm artery, the seven time points of the model group were corresponding to the four courses of atherosclerosis. In accordance with the lipid data of each course of AS and mathematical modeling, this study established a multi-index prediction model of the different processes of AS. Notably, while establishing the model, several indicators were combined with one of four dimension reduction methods, such as principal component logistics regression method, cumulative logistics regression method, Partial least squares-discriminant analysis(PLS-DA), and canonical discriminant analysis (CDA). The error rate of the four methods were 28.5%, 16.22%, 18.24%, and 14.86%, respectively. CDA had the lowest error rate and the best prediction accuracy of the AS different courses for the training and verification sets after 5-fold cross-validation of this model. This study showed that lipidomics combined with mathematical methods could establish a non-invasive and accurate model for the prediction of AS.

Role of Serum cartilage oligomeric matrix protein (COMP) in the diagnosis of rheumatoid arthritis (RA): A case-control study.

OBJECTIVE: To analyse the role of serum cartilage oligomeric matrix protein (COMP) levels in the differential diagnosis of rheumatoid arthritis (RA). METHODS: This case-control study analysed the clinical and laboratory characteristics of patients with RA and healthy control subjects. The diagnostic ability of COMP for RA was evaluated by comparing it with anti-cyclic citrullinated peptide antibody levels. The sensitivity, specificity, positive and negative predictive values were calculated. RESULTS: The study enrolled 82 patients with RA and 34 healthy control subjects. The serum COMP level was significantly higher in patients with RA compared with control subjects (mean ± SD 29.51 ± 9.21 ng/ml versus 17.85 ± 5.55 ng/ml, respectively). The serum COMP level was significantly higher in patients with active RA compared with patients with RA in remission (mean ± SD 33.08 ± 8.80 ng/ml versus 24.94 ± 7.65 ng/ml, respectively). The cut-off value for COMP to discriminate patients with RA from healthy individuals was 21.51 ng/ml (sensitivity 0.817, specificity 0.882, positive predictive value 0.944, negative predictive value 0.667, and accuracy 0.836). CONCLUSION: The serum COMP level has the potential to be used as a biological marker for differentiating between patients with RA and healthy individuals.

EDM1: a novel point mutation in cartilage oligomeric matrix protein gene in a Chinese family with multiple epiphyseal dysplasia.

BACKGROUND: Multiple epiphysis dysplasia (MED) is a common skeletal dysplasia with a significant locus heterogeneity. In the majority of clinically defined cases, mutations have been identified in the gene encoding cartilage algometric matrix protein (COMP). METHODS: Five patients were included in the study. Linkage analysis and mutation analysis of the COMP gene were conducted in the patients and their family members. RESULTS: We have identified a novel mutation in axon 14 of COMP gene in the family. CONCLUSIONS: This mutation produced a severe MED phenotype with marked short stature, early onset osteoarthritis, and remarkable radiographic changes. Our results extended the range of disease-causing mutations in COMP gene and contributed more information about relationship between mutations and phenotype.

Genetic analysis and serum level of cartilage oligomeric matrix protein in patients with pseudoachondroplasia.

BACKGROUND: Pseudoachondroplasia (PSACH) is an autosomal-dominant osteochondrodysplasia due to mutations in the gene encoding cartilage oligomeric matrix protein (COMP). Clinical diagnosis of PSACH is based primarily on family history, physical examination, and radiographic evaluation. There is evidence that decreased serum COMP concentration may serve as a diagnostic marker in PSACH. Here, we investigated the role of this gene and the serum COMP concentration in Chinese patients with PSACH. METHODS: A family with three patients and a sporadic case were recruited. Genomic and phenotypic data were recorded. The diagnosis of PSACH was made on the base of clinical evaluation. The genomic DNA was extracted from peripheral blood leukocytes. The 8-19 exons and flanking intron-exon boundary sequences of COMP were amplified by polymerase chain reaction (PCR) and screened for mutation by direct DNA sequencing. Serum COMP concentrations of 4 patients and age-compatible control group of 20 unrelated healthy subjects were analyzed on the basis of an ELISA Kit for human cartilage oligomeric matrix protein. RESULTS: A deletion (c.1447-1455del) was identified in exon 13 in the sporadic case. The mean serum COMP concentrations of four patients (3.12+/-2.28) were significantly lower than those of control group (10.86+/-2.21, P<0.05). There was no overlap in the distribution of serum COMP concentration between PSACH patients and controls. CONCLUSIONS: Mutations in COMP gene are responsible for the PSACH. Serum COMP concentration may be suggested as an additional diagnostic marker to aid clinical findings in suspected cases of PSACH.