α-mangostin derivatives ameliorated mouse DSS-induced chronic colitis via regulating Th17/Treg balance.

Th17 cell, an important subpopulation of helper T cell, plays an important role in the development of inflammatory bowel disease (IBD) and is thought to be a potential target for the treatment of IBD. In our previous study, we demonstrated that α-mangostin could relieve lupus nephritis via inhibiting Th17 cell function. In our preliminary study, we obtained four derivatives by adding chemical modification of α-mangostin which could also inhibit Th17 cell differentiation in vitro. In this study, we constructed a chronic IBD mouse model and demonstrated the therapeutic effects of α-mangostin and its derivatives as therapeutic agents for IBD. In compounds treating groups, intestinal inflammation showed significant improvement in symptoms which included weight loss, high disease activity index, colon length shorten and the change of intestinal flora. We also found that compounds could effectively either suppress the number of Th17 cell or increase the number of Treg cell detected by flow cytometry, thus reducing the Th17/Treg ratio and suppressing the level of intestinal inflammation. Notably, IL17-F levels, rather than IL17-A, were reduced in the colon of mice of compounds treating groups. Thus, α-mangostin and its derivatives ameliorate DSS-induced chronic colitis in mice by regulating Th17/Treg balance to alleviate intestinal inflammation and can modulate the intestinal microbial community. These results suggest that α-mangostin and its derivatives may be the new therapeutic option for chronic colitis.

Bilateral brain microstructural alterations in patients with left-sided classic trigeminal neuralgia: a diffusion kurtosis imaging study.

OBJECTIVE: White matter microstructural abnormalities in patients with classic trigeminal neuralgia (TN) have been observed. However, the impact of classic TN in both hemispheres, the difference and extent of alterations in bilateral hemispheres, and the relationship between the impaired area and pain conduction are not fully understood. The purpose of this study was to investigate brain microstructural alterations and compare the bilateral hemispheres in patients with unilateral classic TN, as well as to explore their clinical implications. METHODS: The authors performed a cross-sectional study of 36 patients with left classic TN (TN group; age 40-66 years) and 36 healthy controls (HC group; age 40-66 years). Diffusion kurtosis imaging (DKI; b-values = 0, 1250, and 2500 sec/mm2) was performed in all patients using a 3T MRI scanner. The FMRIB Software Library with tract-based spatial statistics was used to analyze intergroup differences in both hemispheres. Atlas-based region of interest analysis was conducted in fiber tracts and gray matter structures. RESULTS: Decreased fractional anisotropy (FA) and increased mean diffusivity in 2.70% and 5.34% of white matter regions, such as the corona radiata, corpus callosum, internal capsule, superior longitudinal fasciculus, and cingulum, were detected in the TN group compared with the HC group (p < 0.05, family-wise error correction). Reduced mean kurtosis (MK), axial kurtosis, and radial kurtosis were detected in the bilateral thalamus in TN patients. The FA and MK values decreased asymmetrically in both cerebral hemispheres. Atlas-based region of interest analysis revealed more pronounced FA and MK reductions in the left thalamus and posterior corona radiata. There were negative associations of disease duration and pain intensity with the MK values in the thalamus, internal capsule, and superior corona radiata. CONCLUSIONS: The authors concluded that unilateral TN could have asymmetrical microstructural alterations in bilateral hemispheres, which might be due to the compromised fiber tract integrity and abnormal neurons and synapses. The thalamus could be an important relay station in the pain conduction and modulation pathway and could have microstructural abnormalities in both the left and right sides. DKI could provide important information on the CNS pathophysiology of TN and assist in prognostic evaluation.

Diffusion Tensor Imaging Reveals Altered Topological Efficiency of Structural Networks in Type-2 Diabetes Patients With and Without Mild Cognitive Impairment.

BACKGROUND: Some patients with type 2 diabetes mellitus (T2DM) progress towards mild cognitive impairment (MCI), while some patients can always maintain normal cognitive function. Network topologic alterations at global and nodal levels between T2DM individuals with and without cognitive impairment may underlie the difference. PURPOSE: To investigate the topological alterations of the whole-brain white matter (WM) structural connectome in T2DM patients with and without MCI and characterize its relationship with disease severity. STUDY TYPE: Cross-sectional and prospective study. SUBJECTS: Forty-four (63.6% females) T2DM patients, 22 with mild cognitive impairment (DM-MCI) and 22 with normal cognition (DM-NC), and 34 (58.8% females) healthy controls (HC). FIELD STRENGTH/SEQUENCE: 3 T/diffusion tensor imaging. ASSESSMENT: Graph theoretical analysis was used to investigate the topological organization of the structural networks. The global topological properties and nodal efficiency were investigated and compared. Relationship between network metrics and clinical measurements was characterized. STATISTICAL TESTS: Student's t-test, chi-square test, ANOVA, partial correlation analyses, and multiple comparisons correction. RESULTS: The global topological organization of WM networks was significantly disrupted in T2DM patients with cognitive impairment (reduced global and local efficiency and increased shortest path length) but not in those with normal cognition, compared with controls. The DM-MCI group had significantly decreased network efficiency compared with the DM-NC group. Compared with controls, decreased nodal efficiency was detected in three regions in DM-NC group. More regions with decreased nodal efficiency were found in the DM-MCI group. Altered global network properties and nodal efficiency of some regions were correlated with diabetic duration, HbA1c levels, and cognitive assessment scores. DATA CONCLUSION: The more disrupted WM connections and weaker organized network are found in DM-MCI patients relative to DM-NC patients and controls. Network analyses provide information for the neuropathology of cognitive decline in T2DM patients. Altered nodal efficiency may act as potential markers for early detection of T2DM-related MCI. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 2.

Urbanization and depressive symptoms among middle-aged and older adults in China.

Aims: Urbanization plays an important role in individuals' health. However, it is difficult to isolate healthy migrant effect between urbanization and health. This study examined the effects of urbanization on depressive symptoms and its possible pathways among Chinese middle-aged and older adults independent of the influence of health-selective migration. Methods: Using the baseline survey of the China Health and Retirement Longitudinal Study, this study compared the depressive symptoms among three groups (urbanized rural residents, rural non-migrants and urban non-migrants). The 10-item Center for Epidemiologic Studies Depression Scale (CESD-10) short form was used to measure depressive symptoms. Logistic regression models and Structural Equation Model (SEM) were applied to examine the association between urbanization and depressive symptoms and the corresponding potential mechanisms. Results: Our final sample contained 11,156 respondents with an average age of 58.91 (SD = 9.48), with 5,142 males (46.09%) and 6,014 females (53.91%). Compared with urbanized rural residents, rural residents were more likely to have depressive symptoms (OR = 1.19, 95% CI = 1.07, 1.32), and urban residents were associated with a decreased risk of depressive symptoms (OR = 0.81, 95% CI: 0.70, 0.94). A large proportion of the association between urbanization and depressive symptoms were mainly mediated by social participation, income and living conditions. Conclusions: Planned urbanization had an independent impact on decreased depressive symptoms. Improvements in social participation, income and living conditions are the main drivers behind this relationship. Additionally, urbanization compensates for the negative impact of depressive symptoms from disadvantaged early life conditions, but it cannot eliminate the gap between urbanized rural people and urban non-migrants.

Systematic Understanding of the Mechanism of Baicalin against Gastric Cancer Using Transcriptome Analysis.

BACKGROUND: Gastric cancer (GC) is the most common type of cancer. It is highly malignant and is characterized by rapid and uncontrolled growth. The antitumour activity of Baicalin was studied in multiple cancers. However, its mechanism of action has not been fully elucidated. We provided a systematic understanding of the mechanism of action of baicalin against GC using a transcriptome analysis of RNA-seq. METHODS: Human GC cells (SGC-7901) were exposed to 200 µg/ml baicalin for 24 h. RNA-seq with a transcriptome, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to identify the antitumour effects of baicalin on SGC-7901 cells in vitro. A protein-protein interaction (PPI) network of differentially expressed genes (DEGs) was constructed. A competitive endogenous RNA (ceRNA) network was constructed and further analysed after validation using qRT-PCR. RESULTS: A total of 68 lncRNAs, 20 miRNAs, and 1648 mRNAs were differentially expressed in baicalin-treated SGC-7901 GC cells. Three lncRNAs, 6 miRNAs, and 7 mRNAs were included in the ceRNA regulatory network. GO analysis revealed that the main DEGs were involved in the biological processes of the cell cycle and cell death. KEGG pathway analysis further suggested that the p53 signalling pathway was involved in the baicalin-induced antitumour effect on SGC-7901 cells. Further confirmation using qPCR indicated that baicalin induced an antitumour effect on SGC-7901 cells, which is consistent with the results of the sequencing data. CONCLUSIONS: In summary, the mechanism of baicalin against GC involves multiple targets and signalling pathways. These results provide new insight into the antitumour mechanism of baicalin and help the development of new strategies to cure GC.

Analysis and Construction of a Competitive Endogenous RNA Regulatory Network of Baicalin-Induced Apoptosis in Human Osteosarcoma Cells.

BACKGROUND: Baicalin is an extract from the traditional Chinese herb Scutellaria baicalensis and has the potential to treat osteosarcoma (OS). However, the transcriptome-level mechanism of baicalin-mediated antitumor effects in OS has not yet been investigated. The aim of this study was to analyze the competitive endogenous RNA (ceRNA) regulatory network involved in baicalin-induced apoptosis of OS cells. METHODS: In this study, CCK-8 and flow cytometry assays were used to detect the antitumor effects of baicalin on human OS MG63 cells. Furthermore, transcriptome sequencing was employed to establish the long noncoding RNA (lncRNA), microRNA (miRNA), and mRNA profiles. RESULTS: Baicalin inhibited MG63 cell proliferation and induced apoptosis. Totals of 58 lncRNAs, 31 miRNAs, and 2136 mRNAs in the baicalin-treated MG63 cells were identified as differentially expressed RNAs compared to those in control cells. Of these, 2 lncRNAs, 3 miRNAs, and 18 mRNAs were included in the ceRNA regulatory network. The differentially expressed RNAs were confirmed by quantitative real-time PCR (qRT-PCR). CONCLUSIONS: By identifying the ceRNA network, our results provide new information about the possible molecular basis of baicalin, which has potential applications in OS treatment.