Objective To investigate whether miR-15b-5p can alleviate airway inflammation in asthma by negatively regulating ubiquitin specific peptidase 9X (USP9X) to down-regulate the expression of phosphatidylinositol 4, 5-diphosphate 3-kinase catalytic subunit α/AKT serine/threonine kinase 1 (PIK3CA/AKT1) pathway. Methods USP9X was predicted to be a direct target of miR-15b-5p by using an online database (miRWalk), and the luciferase reporter gene assay was performed to verify it. Co-immunoprecipitation (CO-IP) was used to verify the direct binding between USP9X and PIK3CA and the role of USP9X and its small molecule inhibitor WP1130 in the deubiquitination of PIK3CA. C57 mice were randomly divided into Control group, OVA group, OVA combined with NC group and miR-15b-5p agomir group, with 10 mice in each group. BEAS-2B cells were induced with interleukin 13 (IL-13) and treated with miR-15b-5p mimic. HE, Masson, PAS, immunohistochemistry, immunofluorescence staining, flow cytometry, Western blot and quantitative real-time PCR(qRT-PCR) were performed. Results It was found that the administration of miR-15b-5p agomir and mimic could reduce peribronchial inflammatory cells and improve airway inflammation, and miR-15b-5p could target negative regulation of USP9X. USP9X could directly bind to PIK3CA and regulate PIK3CA level in a proteasome-dependent manner, and USP9X could deubiquitinate K29-linked PIK3CA protein. Down-regulation of USP9X could increase PIK3CA ubiquitination level. WP1130, a small molecule inhibitor of USP9X, has the same effect as knockdown of USP9X, both of which could increase the ubiquitination level of PIK3CA and reduce the protein level of PIK3CA. Conclusion The miR-15b-5p/USP9X/PIK3CA/AKT1 signaling pathway may provide potential therapeutic targets for asthma.
Animals ; MicroRNAs/metabolism* ; Asthma/pathology* ; Class I Phosphatidylinositol 3-Kinases/genetics* ; Ubiquitin Thiolesterase/metabolism* ; Proto-Oncogene Proteins c-akt/genetics* ; Mice ; Signal Transduction ; Mice, Inbred C57BL ; Humans ; Inflammation/genetics* ; Cell Line ; Female ; Male

Melatonin is widely used as an over-the-counter medication to treat insomnia in children with autism spectrum disorder (ASD) and neurogenetic disorders (NGD). However, there is still a lack of research on its efficacy and safety, and clinical practice standards are to be established. In response, the International Pediatric Sleep Association (IPSA) convened an expert panel and developed a consensus statement:"Melatonin Use in Managing Insomnia in Children with Autism and Other Neurogenetic Disorders-an Assessment by the International Pediatric Sleep Association (IPSA)", which was published in Sleep Medicine, April 2024. The consensus focused on the efficacy and adverse effects of melatonin treatment for insomnia in children with ASD and NGD-including Smith-Magenis syndrome, Rett syndrome, Angelman syndrome, and tuberous sclerosis complex. It systematically reviews randomized controlled trials (RCTs) conducted between 2012 and 2022, and integrates current best clinical practices to formulate 10 consensus recommendations. Despite these contributions, the consensus has limitations: a small number of included RCTs, a lack of grading for evidence quality, and recommendation strength. Furthermore, the study population is primarily composed of children from Western countries. This article seeks to interpret the consensus to improve standardized use of melatonin for insomnia in Chinese children with ASD and NGD, and to provide a reference for the future development of localized evidence-based guidelines.

Autism spectrum disorder(ASD)is a neurodevelopmental disorder starting from early childhood.At present,the age of diagnosis for ASD in children is significantly delayed,typically occurring after two years of age,although behavioral signs or prodromal symptoms can emerge before the age of 12 months.These early indicators gradually evolve into the core symptoms of ASD.It has been well recognized that early screening and intervention can maximally improve its prognosis and promote optimal development of the affected children.Therefore,there has been increasing emphasis on preemptive screening and intervention for prodromal symptoms of ASD before the age of 12 months in clinical practice and research,so as to reduce the symptoms to a normal state to some extent.However,during the prodromal period of ASD,especially before the age of one,preemptive screening and intervention present many challenges.Preemptive screening faces obstacles such as significant individual differences in infant growth and development,incomplete presentation of ASD symptoms,and differing assessment content and criteria;preemptive intervention must overcome challenges like the diversity of screening tools and varying factors of parents.As a result,few research has been conducted in this field.This review mainly introduces preemptive screening tools and intervention techniques for children with ASD in the first year of life,including the intervention used in the British Autism Study of Infant Siblings-video interaction for promoting positive parenting(iBASIS-VIPP),the promoting first relationships,the environmental enrichment for infants,parenting with acceptance and commitment therapy(ENACT),and the adapted response teaching.The application of neuroimaging technology and artificial intelligence technology is also explained to provide reference for relevant research and clinical practice.

Objective To explore the role of Erianin in atopic dermatitis(AD)and its regulatory mechanism involving the high-mobility group box 1(HMGB1)/receptor for advanced glycation end products(RAGE)-Ras homolog gene family member A(RhoA)/Rho-associated protein kinase 1(ROCK1)signaling pathway.Methods An AD model was induced in BALB/c mice using 1-chloro-2,4-dinitrobenzene(DNCB).Skin thickness and spleen and lymph node weight were measured and pathological changes in the back skin and ears were detected using methylamine blue and hematoxylin and eosin staining.Inflammatory factors were detected by enzyme-linked immunosorbent assay.An in vitro model of AD was established in HaCaT cells stimulated by tumor necrosis factor(TNF)-α.Cellular reactive oxygen species(ROS)were detected by flow cytometry and mitochondrial ROS(mtROS)were detected by immunofluorescence assay.Cell apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick-end labeling.HMGB1,RAGE,RhoA,and ROCK1 proteins were detected by Western blot.Results Erianin inhibited the increase in skin thickness,reduced the spleen and lymph node weights,improved the infiltration of inflammatory cells and the degranulation of mast cells,and reduced the levels of inflammatory factors(P＜0.05).Erianin also reduced the production of cellular ROS and mtROS induced by TNF-α in vitro(P＜0.01),and decreased the protein expression of HMGB1,RAGE,RhoA,and ROCK1(P＜0.01).Treatment of HMGB1-stimulated HaCaT cells with a RAGE-specific blocker(TFA)had no effect on HMGB1 expression,while expression levels of RAGE,RhoA,and ROCK1 were decreased(P＜0.01).Cells treated with the Rho kinase inhibitor Y-27632+r-HMGB1 group showed similar result to the TFA+r-HMGB1 group,except for RAGE.Conclusions Erianin relieves AD by regulating the HMGB1/RAGE-RhoA/ROCK signaling pathway.

Nowadays,the incidence of allergic diseases is increasing worldwide,which seriously affects the quality of human life.Recent studies have shown that sex hormones are closely related to the occurrence of allergic diseases.Sex hormones can directly affect the function and development of immune cells,as well as the susceptibility to autoimmune cell responses,resulting in different prevalence and clinical manifestations of allergic diseases in men and women.This article reviews the different roles and potential mechanisms of sex hormones in the occurrence and development of common allergic diseases.In atopic dermatitis,the amount of dehy-droepiandrosterone sulfate into dehydroepiandrosterone sulfate is higher in females than in males.Therefore,females are more suscep-tible to the influence of dehydroepiandrosterone,which inhibits the proliferation of Th2,resulting in a series of clinical symptoms.In allergic asthma,estrogen can aggravate type 2 airway inflammation and androgens can reduce type 2 airway inflammation.Studies have found that there are estrogen and progesterone receptors in the nasal mucosa.When the estrogen concentration increases,the two re-ceptors are also up-regulated,resulting in clinical manifestations such as increased nasal secretions and nasal mucosal swelling.

Objective To explore the mechanism of Glaucocalyxin A(GLA)in inhibiting ovalbumin(OVA)-induced airway remodeling in asthmatic mice through the topoisomerase Ⅱ α(TOP2A)/cyclin-dependent kinase 1(CDK1)signaling pathway.Methods Forty Balb/c mice were randomly divided into 5 groups:the control group,the model group,the low-dose GLA group,the high-dose GLA group and the Dexamethasone group,with 8 mice in each group.The effect of GLA on airway remodeling was examined by immunohistochemical staining,ELISA and other methods,and bioinformatics methods were used to predict new targets of GLA.The action targets of TOP2A were screened using the STRING database,and the interaction relationship between the two was verified by co-immunoprecipitation.In vitro,GLA and siRNA were used to interfere with interleukin-4(IL-4)-stimulated human airway epithelial cells BEAS-2B.The expressions of TOP2A,epidermal growth factor receptor(EGFR),Integrin β1,focal adhesion kinase(FAK),β-catenin,CDK1 and DRP1 were detected by Western Blot.Results GLA intervention could significantly reduce OVA-induced asthma airway remodeling,airway smooth muscle thickening,collagen deposition around the airway,the number of eosinophils in alveolar lavage fluid,the expression of pro-inflammatory cytokines such as IL-4,and the level of serum IgE.The new target of GLA screened out was TOP2A,which was highly expressed in the lung tissue of the asthma airway remodeling model.GLA intervention could down-regulate its expression.In vitro,intervention with GLA and si-TOP2A could significantly down-regulate the expressions of IL-4-induced TOP2A,EGFR,Integrin β1,FAK and β-catenin.Further studies have found that TOP2A had an interaction relationship with CDK1.si-TOP2A could downregulate the expression of CDK1,and knockdown of CDK1 could significantly down-regulate the expression of phosphorylated DRP1.Conclusion GLA may alleviate asthma airway remodeling by targeting the TOP2A/CDK1 signaling pathway,providing experimental evidence for the clinical diagnosis and treatment of asthma airway remodeling in asthma.

Objective To explore the role of Erianin in atopic dermatitis(AD)and its regulatory mechanism involving the high-mobility group box 1(HMGB1)/receptor for advanced glycation end products(RAGE)-Ras homolog gene family member A(RhoA)/Rho-associated protein kinase 1(ROCK1)signaling pathway.Methods An AD model was induced in BALB/c mice using 1-chloro-2,4-dinitrobenzene(DNCB).Skin thickness and spleen and lymph node weight were measured and pathological changes in the back skin and ears were detected using methylamine blue and hematoxylin and eosin staining.Inflammatory factors were detected by enzyme-linked immunosorbent assay.An in vitro model of AD was established in HaCaT cells stimulated by tumor necrosis factor(TNF)-α.Cellular reactive oxygen species(ROS)were detected by flow cytometry and mitochondrial ROS(mtROS)were detected by immunofluorescence assay.Cell apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick-end labeling.HMGB1,RAGE,RhoA,and ROCK1 proteins were detected by Western blot.Results Erianin inhibited the increase in skin thickness,reduced the spleen and lymph node weights,improved the infiltration of inflammatory cells and the degranulation of mast cells,and reduced the levels of inflammatory factors(P＜0.05).Erianin also reduced the production of cellular ROS and mtROS induced by TNF-α in vitro(P＜0.01),and decreased the protein expression of HMGB1,RAGE,RhoA,and ROCK1(P＜0.01).Treatment of HMGB1-stimulated HaCaT cells with a RAGE-specific blocker(TFA)had no effect on HMGB1 expression,while expression levels of RAGE,RhoA,and ROCK1 were decreased(P＜0.01).Cells treated with the Rho kinase inhibitor Y-27632+r-HMGB1 group showed similar result to the TFA+r-HMGB1 group,except for RAGE.Conclusions Erianin relieves AD by regulating the HMGB1/RAGE-RhoA/ROCK signaling pathway.

Autism spectrum disorder(ASD)is a neurodevelopmental disorder starting from early childhood.At present,the age of diagnosis for ASD in children is significantly delayed,typically occurring after two years of age,although behavioral signs or prodromal symptoms can emerge before the age of 12 months.These early indicators gradually evolve into the core symptoms of ASD.It has been well recognized that early screening and intervention can maximally improve its prognosis and promote optimal development of the affected children.Therefore,there has been increasing emphasis on preemptive screening and intervention for prodromal symptoms of ASD before the age of 12 months in clinical practice and research,so as to reduce the symptoms to a normal state to some extent.However,during the prodromal period of ASD,especially before the age of one,preemptive screening and intervention present many challenges.Preemptive screening faces obstacles such as significant individual differences in infant growth and development,incomplete presentation of ASD symptoms,and differing assessment content and criteria;preemptive intervention must overcome challenges like the diversity of screening tools and varying factors of parents.As a result,few research has been conducted in this field.This review mainly introduces preemptive screening tools and intervention techniques for children with ASD in the first year of life,including the intervention used in the British Autism Study of Infant Siblings-video interaction for promoting positive parenting(iBASIS-VIPP),the promoting first relationships,the environmental enrichment for infants,parenting with acceptance and commitment therapy(ENACT),and the adapted response teaching.The application of neuroimaging technology and artificial intelligence technology is also explained to provide reference for relevant research and clinical practice.

Objective To explore the mechanism of Glaucocalyxin A(GLA)in inhibiting ovalbumin(OVA)-induced airway remodeling in asthmatic mice through the topoisomerase Ⅱ α(TOP2A)/cyclin-dependent kinase 1(CDK1)signaling pathway.Methods Forty Balb/c mice were randomly divided into 5 groups:the control group,the model group,the low-dose GLA group,the high-dose GLA group and the Dexamethasone group,with 8 mice in each group.The effect of GLA on airway remodeling was examined by immunohistochemical staining,ELISA and other methods,and bioinformatics methods were used to predict new targets of GLA.The action targets of TOP2A were screened using the STRING database,and the interaction relationship between the two was verified by co-immunoprecipitation.In vitro,GLA and siRNA were used to interfere with interleukin-4(IL-4)-stimulated human airway epithelial cells BEAS-2B.The expressions of TOP2A,epidermal growth factor receptor(EGFR),Integrin β1,focal adhesion kinase(FAK),β-catenin,CDK1 and DRP1 were detected by Western Blot.Results GLA intervention could significantly reduce OVA-induced asthma airway remodeling,airway smooth muscle thickening,collagen deposition around the airway,the number of eosinophils in alveolar lavage fluid,the expression of pro-inflammatory cytokines such as IL-4,and the level of serum IgE.The new target of GLA screened out was TOP2A,which was highly expressed in the lung tissue of the asthma airway remodeling model.GLA intervention could down-regulate its expression.In vitro,intervention with GLA and si-TOP2A could significantly down-regulate the expressions of IL-4-induced TOP2A,EGFR,Integrin β1,FAK and β-catenin.Further studies have found that TOP2A had an interaction relationship with CDK1.si-TOP2A could downregulate the expression of CDK1,and knockdown of CDK1 could significantly down-regulate the expression of phosphorylated DRP1.Conclusion GLA may alleviate asthma airway remodeling by targeting the TOP2A/CDK1 signaling pathway,providing experimental evidence for the clinical diagnosis and treatment of asthma airway remodeling in asthma.

Nowadays,the incidence of allergic diseases is increasing worldwide,which seriously affects the quality of human life.Recent studies have shown that sex hormones are closely related to the occurrence of allergic diseases.Sex hormones can directly affect the function and development of immune cells,as well as the susceptibility to autoimmune cell responses,resulting in different prevalence and clinical manifestations of allergic diseases in men and women.This article reviews the different roles and potential mechanisms of sex hormones in the occurrence and development of common allergic diseases.In atopic dermatitis,the amount of dehy-droepiandrosterone sulfate into dehydroepiandrosterone sulfate is higher in females than in males.Therefore,females are more suscep-tible to the influence of dehydroepiandrosterone,which inhibits the proliferation of Th2,resulting in a series of clinical symptoms.In allergic asthma,estrogen can aggravate type 2 airway inflammation and androgens can reduce type 2 airway inflammation.Studies have found that there are estrogen and progesterone receptors in the nasal mucosa.When the estrogen concentration increases,the two re-ceptors are also up-regulated,resulting in clinical manifestations such as increased nasal secretions and nasal mucosal swelling.