Abnormal degree centrality as a potential imaging biomarker for ischemic stroke: A resting-state functional magnetic resonance imaging study.

OBJECTIVE: To explore degree centrality (DC) abnormalities in ischemic stroke patients and determine whether these abnormalities have potential value in understanding the pathological mechanisms of ischemic stroke patients. METHODS: Sixteen ischemic stroke patients and 22 healthy controls (HCs) underwent resting state functional magnetic resonance imaging (rs-fMRI) scanning, and the resulting data were subjected to DC analysis. Then we conducted a correlation analysis between DC values and neuropsychological test scores, including Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE). Finally, extracted the abnormal DC values of brain regions and defined them as features for support vector machine (SVM) analysis. RESULTS: Compared with HCs, ischemic stroke patients showed increased DC in the bilateral supplementary motor area, and median cingulate and paracingulate gyri and decreased DC in the left postcentral gyrus, right calcarine fissure and surrounding cortex, lingual gyrus, and orbital parts of the right superior frontal gyrus and bilateral cuneus. Correlation analyses revealed that DC values in the right lingual gyrus, calcarine fissure and surrounding cortex, and orbital parts of the right superior frontal gyrus were positively correlated with the MMSE scores. The SVM classification of the DC values achieved an area under the curve (AUC) of 0.93, an accuracy of 89.47%. CONCLUSION: Our research results indicate that ischemic stroke patients exhibit abnormalities in the global connectivity mechanisms and patterns of the brain network. These abnormal changes may provide neuroimaging evidence for stroke-related motor, visual, and cognitive impairments, contribute to a deeper comprehension of the underlying pathophysiological mechanisms implicated in ischemic stroke.

Glymphatic system dysfunction in middle-aged and elderly chronic insomnia patients with cognitive impairment evidenced by diffusion tensor imaging along the perivascular space (DTI-ALPS).

BACKGROUND: Chronic insomnia impairs the glymphatic system and may lead to cognitive impairment and dementia in elderly population. The diffusion tensor image analysis along the perivascular space (DTI-ALPS) has been proposed as a non-invasive method to measure the activity of human brain glymphatic. We aim to explore whether glymphatic function is impaired in middle-aged and elderly chronic insomnia individuals and to identify the relationships between glymphatic dysfunction and cognitive impairment. METHODS: A total of 33 chronic insomnia patients (57.36 ± 5.44 years, 30 females) and 20 age- and sex-matched healthy controls (57.95 ± 5.78 years, 16 females) were prospectively enrolled between May 2022 and January 2023. All participants completed MRI screening, cognition and sleep assessments, and DTI-ALPS index analysis. RESULTS: Our findings revealed that the DTI-ALPS index was significantly difference among the chronic insomnia patients with impaired cognition group (1.32 ± 0.14), with normal cognition group (1.46 ± 0.09), and healthy controls (1.61 ± 0.16) (p = 0.0012, p < 0.0001, p = 0.0008, respectively). Mini-Mental State Examination (MMSE) scores of chronic insomnia patients with cognitive impairment were positively correlated with the DTI-ALPS index (Partial correlation analyses after correction for age, sex, education level and duration of chronic insomnia: r = 0.78, p = 0.002). DTI-ALPS had moderate accuracy in distinguishing chronic insomnia patients with cognitive impairment from those with normal cognition. DATA CONCLUSION: The glymphatic system dysfunction is involved in chronic insomnia among middle-aged and elderly individuals, and it has been found to be correlated with cognitive decline.

Changes in Resting-State Networks in Children with Growth Hormone Deficiency.

Purpose: Growth hormone deficiency (GHD) refers to the partial or complete lack of growth hormone. Short stature and slow growth are characteristic of patients with GHD. Previous neuroimaging studies have suggested that GHD may cause cognitive and behavioral impairments in patients. Resting-state networks (RSNs) are regions of the brain that exhibit synchronous activity and are closely related to our cognition and behavior. Therefore, the purpose of the current study was to explore cognitive and behavioral abnormalities in children with GHD by investigating changes in RSNs. Methods: Resting-state functional magnetic resonance imaging (rs-fMRI) data of 26 children with GHD and 15 healthy controls (HCs) were obtained. Independent component analysis was used to identify seven RSNs from rs-fMRI data. Group differences in RSNs were estimated using two-sample t-tests. Correlation analysis was employed to investigate the associations among the areas of difference and clinical measures. Results: Compared with HCs, children with GHD had significant differences in the salience network (SN), default mode network (DMN), language network (LN), and sensorimotor network (SMN). Moreover, within the SN, the functional connectivity (FC) value of the right posterior supramarginal gyrus was negatively correlated with the adrenocorticotropic hormone and the FC value of the left anterior inferior parietal gyrus was positively correlated with insulin-like growth factor 1. Conclusions: These results suggest that alterations in RSNs may account for abnormal cognition and behavior in children with GHD, such as decreased motor function, language withdrawal, anxiety, and social anxiety. These findings provide neuroimaging support for uncovering the pathophysiological mechanisms of GHD in children. Impact statement Children with growth hormone deficiency (GHD) generally experience cognitive and behavioral abnormalities. However, there are few neuroimaging studies on children with GHD. Moreover, prior research has not investigated the aberrant brain function in patients with GHD from the perspective of brain functional networks. Therefore, this study employed the independent component analysis method to investigate alterations within seven commonly observed resting-state networks due to GHD. The results showed that children with GHD had significant differences in the salience network, default mode network, language network, and sensorimotor network. This provides neuroimaging support for revealing the pathophysiological mechanisms of GHD in children.

Dynamic analysis of amplitude of low-frequency fluctuation in children with growth hormone deficiency.

OBJECTIVE: Growth hormone (GH) affects brain activities and promotes growth and development. GH is a peptide hormone secreted by the anterior pituitary gland and is tied to behavior and cognitive function. Growth hormone deficiency (GHD) is the most common type of pathological short stature in children. Existing studies provide evidence that GHD may impact functional brain activities. The aim of this study was to investigate dynamic local brain activity in GHD children. METHOD: In this study, we combined amplitude of low-frequency fluctuations (ALFF) and sliding-window techniques to examine the local brain activity of children with GHD. The resting-state functional magnetic resonance imaging (fMRI) data were collected from 26 children with GHD and 15 age- and sex-matched healthy controls (HC). RESULT: Our results showed significant abnormal temporal variability of dynamic ALFF in widespread regions in children with GHD, primarily in the frontal gyrus, temporal gyrus, and parietal lobule. CONCLUSION: The dALFF can capture dynamic changes in brain spontaneous activity, which are related to behavior and cognition. Based on this dynamic local brain activity, the results of this study provide a better understanding of the pathophysiological mechanism in children with GHD.

Frequency Dependent Changes of Regional Homogeneity in Children with Growth Hormone Deficiency.

Abnormal spontaneous neural activity in children with growth hormone deficiency (GHD) has been found in previous resting-state functional magnetic resonance imaging (rs-fMRI) studies. Nevertheless, the spontaneous neural activity of GHD in different frequency bands is still unclear. Here, we combined rs-fMRI and regional homogeneity (ReHo) methods to analyze the spontaneous neural activity of 26 GHD children and 15 healthy controls (HCs) with age- and sex-matching in four frequency bands: slow-5 (0.014-0.031 Hz), slow-4 (0.031-0.081 Hz), slow-3 (0.081-0.224 Hz), and slow-2 (0.224-0.25 Hz). In the slow-5 band, GHD children compared with HCs displayed higher ReHo in the left dorsolateral part of the superior frontal gyrus, triangular part of the inferior frontal gyrus, precentral gyrus and middle frontal gyrus, and right angular gyrus, while lower ReHo in the right precentral gyrus, and several medial orbitofrontal regions. In the slow-4 band, GHD children relative to HCs revealed increased ReHo in the right middle temporal gyrus, whereas reduced ReHo in the left superior parietal gyrus, right middle occipital gyrus, and bilateral medial parts of the superior frontal gyrus. In the slow-2 band, compared with HCs, GHD children showed increased ReHo in the right anterior cingulate gyrus, and several prefrontal regions, while decreased ReHo in the left middle occipital gyrus, and right fusiform gyrus and anterior cingulate gyrus. Our findings demonstrate that regional brain activity in GHD children exhibits extensive abnormalities, and these abnormalities are related to specific frequency bands, which may provide bases for understanding its pathophysiology significance.

Frequency specificity in the amplitude of low frequency oscillations in patients with white matter lesions.

Previous studies have reported that patients with white matter lesions (WMLs) have abnormal spontaneous brain activity in the resting state. However, the spontaneous neuronal activity of specific frequency bands in WMLs patients is unknown. Here, we included 16 WMLs patients and 13 gender and age-matched healthy controls (HCs) underwent resting-state magnetic resonance imaging (rs-fMRI) scan and studied the specificity of the amplitude of low-frequency fluctuations (ALFF) in WMLs patients in the slow-5 (0.01-0.027 Hz), slow-4 (0.027-0.073 Hz), and typical (0.01-0.08 Hz) frequency bands. In addition, ALFF values of different frequency bands were extracted as classification features and support vector machines (SVM) were used to classify WMLs patients. In all three frequency bands, significant increases in ALFF values in WMLs patients were observed in the cerebellum. In the slow-5 band, the ALFF values of the left anterior cingulate and paracingulate gyri (ACG), and the right precentral gyrus, rolandic operculum and inferior temporal gyrus in WMLs patients were lower than those in HCs. In the slow-4 band, ALFF values were lower in WMLs patients than in HCs at the left ACG, the right median cingulate and paracingulate gyri, parahippocampal gyrus, caudate nucleus, and the bilateral lenticular nucleus, putamen. In the SVM classification model, the classification accuracy of slow-5, slow-4 and typical frequency bands is 75.86%, 86.21% and 72.41%, respectively. The results indicate that the ALFF abnormalities in WMLs patients have frequency specificity, and the ALFF abnormalities in the slow-4 frequency band may serve as imaging markers for WMLs.

DNMT1/miR-130a/ZEB1 Regulatory Pathway Affects the Inflammatory Response in Lipopolysaccharide-Induced Sepsis.

Sepsis is a global health care issue that affects millions of people. DNA methyltransferase I (DNMT1)-mediated DNA methylation is involved in a number of human diseases by affecting many types of cellular progression events. However, the role and underlying molecular mechanism of DNMT1 in development of sepsis remain largely unknown. Lipopolysaccharide (LPS) induced lung fibrosis in the sepsis mouse model, and DNMT1 was upregulated in lung tissues of a sepsis mouse model compared with lung tissues from control mice. Then, this study demonstrated that LPS induced the production of interleukin (IL)-7 and tumor necrosis factor (TNF)-α and promoted DNMT1 expression in primary type II alveolar epithelial cells (AECII cells). Knockdown of DNMT1 inhibited IL-7 and TNF-α secretion in AECII cells exposed to LPS. Further study demonstrated that DNMT1 repressed the expression of miR-130a in AECII cells with or without LPS exposure. Next, this study demonstrated that miR-130a inhibited ZEB1 expression in AECII cells exposed to LPS. Ultimately, this study revealed the role of the DNMT1/miR-130a/ZEB1 regulatory pathway in AECII cells exposed to LPS. Overall, our data revealed that LPS induced the secretion of inflammatory factors by modulating the DNMT1/miR-130a/ZEB1 regulatory pathway in AECII cells, thus providing a novel theoretical basis that might be beneficial for establishment of diagnostic and therapeutic strategies for sepsis.

Regional homogeneity abnormalities of resting state brain activities in children with growth hormone deficiency.

Growth hormone deficiency (GHD) is a common developmental disorder in children characterized by low levels of growth hormone secretion, short stature, and multiple cognitive and behavioral problems, including hyperactivity, anxiety, and depression. However, the pathophysiology of this disorder remains unclear. In order to investigate abnormalities of brain functioning in children with GHD, we preformed functional magnetic resonance imaging and regional homogeneity (ReHo) analysis in 26 children with GHD and 15 age- and sex-matched healthy controls (HCs) in a resting state. Compared with HCs, children with GHD exhibited increased ReHo in the left putamen and decreased ReHo in the right precentral gyrus, reflecting a dysfunction of inhibitory control. Decreased ReHo was also identified in the orbital parts of the bilateral superior frontal gyrus and the medial part of the left superior frontal gyrus, a finding that correlated with the inappropriate anxiety and depression that are observed in this patient population. Our results provide imaging evidence of potential pathophysiologic mechanisms for the cognitive and behavioral abnormalities of children with GHD.

Association of serum asprosin concentrations with obstructive sleep apnea syndrome.

OBJECTIVE: Asprosin, a recently discovered adipokine, stimulates the release of hepatic glucose. The purpose of the current research was to determine the relation between serum asprosin and obstructive sleep apnea syndrome (OSAS). METHODS: The current investigation enrolled 152 patients with OSAS and 97 control subjects. Serum asprosin concentrations were measured and analyzed. RESULTS: Higher serum asprosin concentrations were found in patients with OSAS than in the controls. Logistic regression analysis demonstrated that serum asprosin concentrations were associated with an increased risk of OSAS. Patients with severe OSAS had significantly increased asprosin compared to mild and moderate groups. The group with moderate OSAS showed higher serum asprosin levels than the group with mild OSAS. Pearson correlation analysis demonstrated a positive relation between serum asprosin and disease severity. Simple linear regression analyses showed a significant correlation between serum asprosin with body mass index (BMI), fasting plasma glucose (FPG), homeostasis model assessment of insulin resistance (HOMA-IR), triglycerides (TG), and apnea-hypopnea index (AHI), and negatively correlated with high-density lipoprotein cholesterol (HDL-C). Multiple linear regression analysis revealed a significant correlation between serum asprosin with BMI, FPG, HOMA-IR, TG, AHI, and HDL-C. CONCLUSION: There is a significant correlation between serum asprosin with the presence and severity of OSAS.

Abnormal amplitude of spontaneous low-frequency fluctuation in children with growth hormone deficiency: A resting-state functional magnetic resonance imaging study.

Growth hormone deficiency (GHD) is a developmental disorder caused by the partial or complete deficiency of growth hormone secreted by the pituitary gland, or its receptor. Patients with GHD are characterized by short stature, slow growth, and certain cognitive and behavioral abnormalities. Previous behavioral and neuroimaging studies indicate that GHD might affect the brain functional activity associated with cognitive and behavioral abilities. We thus investigated the spontaneous neural activity in children with GHD using amplitude of low-frequency fluctuation (ALFF) analysis. ALFF was calculated based on resting-state functional magnetic resonance imaging (rs-fMRI) data in 26 children with GHD and 15 age- and sex-matched healthy controls (HCs). Comparative analysis revealed that the ALFF of the right lingual gyrus and angular gyrus were significantly increased, while the ALFF of the right dorsolateral superior frontal gyrus, the left postcentral gyrus, superior parietal gyrus and middle temporal gyrus were significantly decreased in children with GHD relative to HCs. These findings support the presence of abnormal brain functional activity in children with GHD, which may account for the abnormal cognition and behavior, such as aggression, somatic complaints, attention deficits, and language withdrawal. This study provides imaging evidence for future studies on the pathophysiological mechanisms of abnormal behavior and cognition in children with GHD.

Alterations of functional and structural connectivity in patients with brain metastases.

Metastases are the most prevalent tumors in the brain and are commonly associated with high morbidity and mortality. Previous studies have suggested that brain tumors can induce a loss of functional connectivity and alter the brain network architecture. Little is known about the effect of brain metastases on whole-brain functional and structural connectivity networks. In this study, 14 patients with brain metastases and 16 healthy controls underwent resting state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI). We constructed functional connectivity network using rs-fMRI signal correlations and structural connectivity network using DTI tractography. Graph theoretical analysis was employed to calculate network properties. We further evaluated the performance of brain networks after metastases resection by a simulated method. Compared to healthy controls, patients with brain metastases showed an altered "small-world" architecture in both functional and structural connectivity networks, shifting to a more randomness organization. Besides, the coupling strength of functional-structural connectivity was decreased in patients. After removing nodes infiltrated by metastases, aggravated disruptions were found in both functional and structural connectivity networks, and the alterations of network properties correlated with the removed hubs number. Our findings suggest that brain metastases interfere with the optimal network organization and relationship of functional and structural connectivity networks, and tumor resection involving hubs could cause a worse performance of brain networks. This study provides neuroimaging guidance for neurosurgical planning and postoperative assessment of brain metastases from the aspect of brain networks.

Presurgical localization and spatial shift of resting state networks in patients with brain metastases.

Brain metastases are the most prevalent cerebral tumors. Resting state networks (RSNs) are involved in multiple perceptual and cognitive functions. Therefore, precisely localizing multiple RSNs may be extremely valuable before surgical resection of metastases, to minimize neurocognitive impairments. Here we aimed to investigate the reliability of independent component analysis (ICA) for localizing multiple RSNs from resting-state functional MRI (rs-fMRI) data in individual patients, and further evaluate lesion-related spatial shifts of the RSNs. Twelve patients with brain metastases and 14 healthy controls were recruited. Using an improved automatic component identification method, we successfully identified seven common RSNs, including: the default mode network (DMN), executive control network (ECN), dorsal attention network (DAN), language network (LN), sensorimotor network (SMN), auditory network (AN) and visual network (VN), in both individual patients and controls. Moreover, the RSNs in the patients showed a visible spatial shift compared to those in the controls, and the spatial shift of some regions was related to the tumor location, which may reflect a complicated functional mechanism - functional disruptions and reorganizations - caused by metastases. Besides, higher cognitive networks (DMN, ECN, DAN and LN) showed significantly larger spatial shifts than perceptual networks (SMN, AN and VN), supporting a functional dichotomy between the two network groups even in pathologic alterations associated with metastases. Overall, our findings provide evidence that ICA is a promising approach for presurgical localization of multiple RSNs from rs-fMRI data in individual patients. More attention should be paid to the spatial shifts of the RSNs before surgical resection.

Benign ependymoma with extensive intracranial and spinal cerebrospinal fluid dissemination: case report and literature review.

Myxopapillary ependymoma (MPE) is a rare variant of ependymoma that is most commonly located in the cauda equina and filum terminale. We present a case of 23-year-old man diagnosed with MPE in the fourth ventricle and sacral canal area with extensive disseminated lesions along the cerebrospinal ventricular system. Additionally, a molecular pathological diagnosis was performed. The patient underwent a craniotomy and a lumbar laminectomy. In the course of 18 months of follow-up, the patient have recovered very well.

Altered connectivity patterns among resting state networks in patients with ischemic white matter lesions.

White matter lesions (WMLs) have been associated with cognitive and motor decline. Resting state networks (RSNs) are spatially coherent patterns in the human brain and their interactions sustain our daily function. Therefore, investigating the altered intra- and inter-network connectivity among the RSNs may help to understand the association of WMLs with impaired cognitive and motor function. Here, we assessed alterations in functional connectivity patterns based on six well-defined RSNs-the default mode network (DMN), dorsal attention network (DAN), frontal-parietal control network (FPCN), auditory network (AN), sensory motor network (SMN) and visual network (VN)-in 15 patients with ischemic WMLs and 15 controls. In the patients, Spearman's correlation analysis was further performed between these alterations and cognitive test scores, including Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores. Our results showed wide alterations of inter-network connectivity mainly involving the SMN, DMN, FPCN and DAN, and some alterations correlated with cognitive test scores in the patients. The reduced functional connectivities in the SMN-AN, SMN-VN, FPCN-AN, DAN-VN pairs may account for the cognitive and motor decline in patients with ischemic WMLs, while the increased functional connectivities in the DMN-AN, DMN-FPCN and DAN-FPCN pairs may reflect a functional network reorganization after damage to white matter. It is unexpected that altered intra-network connectivities were found within the AN and VN, which may explain the impairments in verbal fluency and information retrieval associated with WMLs. This study highlights the importance of functional connectivity in understanding how WMLs influence cognitive and behavior dysfunction.

Abnormal cortical functional activity in patients with ischemic white matter lesions: A resting-state functional magnetic resonance imaging study.

There is increasing evidence that white matter lesions (WMLs) are associated with cognitive impairments. The purpose of this study was to explore the relationship of WMLs with cognitive impairments from the aspect of cortical functional activity. Briefly, Sixteen patients with ischemic WMLs and 13 controls participated in this study. A regional homogeneity (ReHo) approach was used to investigate altered neural coherence in patients with ischemic WMLs during the resting state. A correlation analysis was further performed between regions with altered ReHo and cognitive test scores, including Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA), in the patient group. Finally, we found regions with altered ReHo values in patients with ischemic WMLs to be involved in default mode network (DMN), frontal-parietal control network (FPCN), dorsal attention network (DAN), motor network and right temporal cortex. Moreover, some altered regions belonging to DMN, FPCN and motor network were significantly correlated with cognitive test scores. Our results provide neuroimaging evidence for the impairments of memory, attention, executive and motor function in patients with ischemic WMLs. It is interesting to note that the decreased ReHo was mainly in the anterior brain regions, while increased ReHo in the posterior brain regions, which may indicate a failure down regulation of spontaneous activity in posterior regions. In summary, this study indicates an important role of specific cortical dysfunction in cognitive associated with WMLs.

An Investigation of the Differences and Similarities between Generated Small-World Networks for Right- and Left-Hand Motor Imageries.

In this study, small-world network analysis was performed to identify the similarities and differences between functional brain networks for right- and left-hand motor imageries (MIs). First, Pearson correlation coefficients among the nodes within the functional brain networks from healthy subjects were calculated. Then, small-world network indicators, including the clustering coefficient, the average path length, the global efficiency, the local efficiency, the average node degree, and the small-world index, were generated for the functional brain networks during both right- and left-hand MIs. We identified large differences in the small-world network indicators between the functional networks during MI and in the random networks. More importantly, the functional brain networks underlying the right- and left-hand MIs exhibited similar small-world properties in terms of the clustering coefficient, the average path length, the global efficiency, and the local efficiency. By contrast, the right- and left-hand MI brain networks showed differences in small-world characteristics, including indicators such as the average node degree and the small-world index. Interestingly, our findings also suggested that the differences in the activity intensity and range, the average node degree, and the small-world index of brain networks between the right- and left-hand MIs were associated with the asymmetry of brain functions.

Abnormal functional connectivity density in patients with ischemic white matter lesions: An observational study.

White matter lesions (WMLs) are frequently detected in elderly people. Previous structural and functional studies have demonstrated that WMLs are associated with cognitive and motor decline. However, the underlying mechanism of how WMLs lead to cognitive decline and motor disturbance remains unclear. We used functional connectivity density mapping (FCDM) to investigate changes in brain functional connectivity in 16 patients with ischemic WMLs and 13 controls. Both short- and long-range FCD maps were computed, and group comparisons were performed between the 2 groups. A correlation analysis was further performed between regions with altered FCD and cognitive test scores (Mini-Mental State Examination [MMSE] and Montreal Cognitive Assessment [MoCA]) in the patient group. We found that patients with ischemic WMLs showed reduced short-range FCD in the temporal cortex, primary motor cortex, and subcortical region, which may account for inadequate top-down attention, impaired motor, memory, and executive function associated with WMLs. The positive correlation between primary motor cortex and MoCA scores may provide evidence for the influences of cognitive function on behavioral performance. The inferior parietal cortex exhibited increased short-range FCD, reflecting a hyper bottom-up attention to compensate for the inadequate top-down attention for language comprehension and information retrieval in patients with WMLs. Moreover, the prefrontal and primary motor cortex showed increased long-range FCD and the former positively correlated with MoCA scores, which may suggest a strategy of cortical functional reorganization to compensate for motor and executive deficits. Our findings provide new insights into how WMLs cause cognitive and motor decline from cortical functional connectivity perspective.

Crocetin Activates Foxp3 Through TIPE2 in Asthma-Associated Treg Cells.

BACKGROUND/AIMS: Regulatory T cells (Treg) are critical regulators of asthma. Crocetin is isolated from Chinese herb saffron and is a natural carotenoid dicarboxylic acid with anti-inflammatory potential. However, the effects of Crocetin on asthma as well as the underlying mechanisms have not been studied. METHODS: We used Crocetin to treat mice with established ovalbumin (OVA)-induced asthma. We purified CD4+CD25+ Treg cells by flow cytometry and analyzed the levels of two immunoregulatory proteins Foxp3 and tumor necrosis factor (TNF)-alpha-induced protein 8-like 2 (TIPE2) in Treg cells. We depleted either Foxp3 or TIPE2 in mouse lung through lentivirus-mediated delivery of shRNA, and analyzed their effects on severity of asthma and Treg cells after Crocetin treatment. RESULTS: Crocetin treatment significantly reduced the severity of an ovalbumin (OVA)-induced asthma in mice. Moreover, Crocetin significantly increased the levels of TIPE2 and Foxp3 in Treg cells and the number of Treg cells. Depletion of Foxp3 abolished the increased in Treg cells, and the effects of Crocetin on the severity of asthma, without affecting TIPE2 levels in Treg cells. On the other hand, depletion of TIPE2 abolished both the increased in Treg cells and the effects of Crocetin on the severity of asthma, through suppressing Foxp3. CONCLUSION: Crocetin may activate Foxp3 through TIPE2 in asthma-associated Treg cells to mitigate the severity of asthma.