Chang-wei-qing, a Chinese herbal formula, ameliorates colitis-associated tumour development via inhibiting NF-κB and STAT3 signalling pathway.

CONTEXT: Chang-wei-qing (CWQ) is a Chinese herbal recipe with clinical efficacy. However, the molecular mechanism underlying its recognized therapeutic benefits against colorectal cancer is still elusive. OBJECTIVE: To investigate the potential beneficial effects of CWQ in drug-induced colitis-associated cancer (CAC) model and its mechanistic involvements in this disease. MATERIALS AND METHODS: Colitis-associated cancer model was induced by azoxymethane (AOM) and dextran sulphate sodium (DSS). CWQ was administrated by gavage. Colon length and tumour size were determined after resection. The colitis was systematically scored. The microbiota and population of Faecalibacterium prausnitzii (F. prausnitzii) Hauduroy & Duncan was analysed by quantitative polymerase chain reaction (PCR). ß-Glucuronidase, d-lactose and endotoxin were determined with commercially available kits. Pro-inflammatory cytokines were analysed in the colon tissues. Relative protein expressions were determined by Western blotting. RESULTS: High concentration CWQ significantly restored the colon length, decreased tumour number and size (1.7 ± 0.6 vs. 2.8 ± 0.4 mm, p < 0.01) and reduced colitis score (11.8 ± 2.1 vs. 18.2 ± 2.3, p < 0.01). CWQ also suppressed expansion of F. prausnitzii population (0.029 ± 0.015% vs. 0.052 ± 0.019%, p < 0.01). CWQ greatly inhibited the activity of ß-glucuronidase and leakage of d-lactose and endotoxin. Meanwhile, the pro-inflammatory cytokines were remarkably decreased in CAC mice in response to CWQ treatment. We further demonstrated that CWQ inhibited both NF-κB and STAT3 signalling. CONCLUSIONS: We for the first time demonstrated the antitumour properties of CWQ in vivo via inhibiting NF-κB and STAT3 signalling.

Exploring the transcriptomic landscape of moyamoya disease and systemic lupus erythematosus: insights into crosstalk genes and immune relationships.

Background: Systemic Lupus Erythematosus (SLE) is acknowledged for its significant influence on systemic health. This study sought to explore potential crosstalk genes, pathways, and immune cells in the relationship between SLE and moyamoya disease (MMD). Methods: We obtained data on SLE and MMD from the Gene Expression Omnibus (GEO) database. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were conducted to identify common genes. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on these shared genes. Hub genes were further selected through the least absolute shrinkage and selection operator (LASSO) regression, and a receiver operating characteristic (ROC) curve was generated based on the results of this selection. Finally, single-sample Gene Set Enrichment Analysis (ssGSEA) was utilized to assess the infiltration levels of 28 immune cells in the expression profile and their association with the identified hub genes. Results: By intersecting the important module genes from WGCNA with the DEGs, the study highlighted CAMP, CFD, MYO1F, CTSS, DEFA3, NLRP12, MAN2B1, NMI, QPCT, KCNJ2, JAML, MPZL3, NDC80, FRAT2, THEMIS2, CCL4, FCER1A, EVI2B, CD74, HLA-DRB5, TOR4A, GAPT, CXCR1, LAG3, CD68, NCKAP1L, TMEM33, and S100P as key crosstalk genes linking SLE and MMD. GO analysis indicated that these shared genes were predominantly enriched in immune system process and immune response. LASSO analysis identified MPZL3 as the optimal shared diagnostic biomarkers for both SLE and MMD. Additionally, the analysis of immune cell infiltration revealed the significant involvement of activation of T and monocytes cells in the pathogenesis of SLE and MMD. Conclusion: This study is pioneering in its use of bioinformatics tools to explore the close genetic relationship between MMD and SLE. The genes CAMP, CFD, MYO1F, CTSS, DEFA3, NLRP12, MAN2B1, NMI, QPCT, KCNJ2, JAML, MPZL3, NDC80, FRAT2, THEMIS2, CCL4, FCER1A, EVI2B, CD74, HLA-DRB5, TOR4A, GAPT, CXCR1, LAG3, CD68, NCKAP1L, TMEM33, and S100P have been identified as key crosstalk genes that connect MMD and SLE. Activation of T and monocytes cells-mediated immune responses are proposed to play a significant role in the association between MMD and SLE.

Comprehensive Serum Proteomic and Metabolomic Profiles of Pediatric Patients with Moyamoya Disease Reveal Core Pathways.

Background: Moyamoya disease (MMD) signifies a cerebrovascular disorder with obscure origin and a more rapid and severe progression in children than adults. This investigation aims to uncover age-associated distinctions through proteomic and metabolomic profiling to gain insights into the underlying mechanisms of MMD. Methods: Twelve MMD patients-six children and six adults-along with six healthy controls (HC), participated, each providing a 10 mL blood sample. Serum proteomic and metabolomic analyses were conducted using ultra-performance liquid chromatography and high-resolution mass spectrometry, complemented by bioinformatics to identify differential biomolecules and their interactions. Pathway implications were ascertained using GO and KEGG enrichment analysis. Results: Notable proteomic and metabolomic discrepancies were observed between pediatric and adult MMD subjects. A total of 235 and 216 proteins varied in adult and pediatric cases compared to HCs, with 73 proteins shared. In addition, 129 and 74 anionic, plus 96 and 104 cationic metabolites, were differentially expressed in the pediatric and adult groups, respectively, with 34 anionic and 28 cationic metabolites in common. Age-specific biomolecules further characterized these distinctions. Enrichment analysis pinpointed immunity and inflammation pathways, with vitamin digestion and absorption highlighted as pivotal in pediatric MMD. Conclusion: This study unveils distinct metabolic and proteomic patterns within pediatric and adult MMD patients. The critical role of the vitamin digestion and absorption pathway in the pathogenesis of pediatric MMD offers novel insight into disease mechanisms.

Association Between Polymorphisms in Estrogen Receptor Genes and Depression in Women: A Meta-Analysis.

Objective: It is suggested that estrogen receptors (ERs) might be associated with the disproportionate vulnerability of women to depressive episodes. Several variants in ER-alpha (ERα) and ER-beta (ERß) have been linked to depression, but the results were not consistent. Hence, we conducted a meta-analysis to evaluate the association between ERα/ERß and depression in a cohort of women. Methods: A comprehensive literature search was performed in public databases. The genetic association between polymorphisms in Erα/ERß and depression risk in a cohort of women was evaluated by odds ratios (ORs) and 95% confidence intervals (CIs). Cochran's Q test and the I2 index were used to evaluate heterogeneity. Results: In total, 10 studies and 4 SNPs (rs2234693, rs9340799, rs4986938, rs1256049) were included in our meta-analysis. rs2234693 genotype was significantly associated with the risk of depression in women by dominant model (CC + CT vs TT, OR = 1.30, 95% CI: 1.09-1.55, p = 0.0031), recessive model (CC vs CT + TT, OR = 1.64, 95% CI: 1.00-2.67, p = 0.0478), additive model (CC vs TT, OR = 1.93, 95% CI: 1.12-3.35, p = 0.0189) and allelic model (C vs T, OR = 1.24, 95% CI: 1.10-1.39, p = 0.0003). For rs9340799, the frequencies of risk genotypes according to the dominant (GG + GA vs AA, OR = 1.47, 95% CI = 1.10-1.98, p = 0.0096, I2 = 0%, p = 0.43) and allelic (G vs A, OR = 1.33, 95% CI: 1.04-1.69, p = 0.0236, I2 = 0%, p = 0.39) models were significantly lower in women with depression than in controls within the Asian subgroup. For rs1256049, risk genotypes were significantly more frequent in depressed subjects than in controls under the dominant model (AA+ GA vs GG, OR = 1.62, 95% CI: 1.19-2.21, p = 0.0024) and the allelic model (A vs G, OR = 1.35, 95% CI: 1.07-1.72, p = 0.012) after sensitivity analysis by omitting one study which induce the heterogeneity. Conclusions: The current meta-analysis is the first and most comprehensive investigation of the association between ERs and depression in women, and the findings support the concept that ERs participate in the etiology of sex heterogeneity in depression.

Quercetin Inhibits Tumorigenesis of Colorectal Cancer Through Downregulation of hsa_circ_0006990.

Quercetin can significantly inhibit the progression of colorectal cancer (CRC). However, its specific mechanism remains largely unclear. In this study, we aimed to explore the correlation among quercetin, tumour-associated macrophages (TAMs) and circular RNAs (circRNAs) in the progression of CRC and to present a novel strategy for the treatment of CRC. In this study, we revealed that quercetin could suppress the autophagy of M2-TAMs and induced their differentiation into M1-TAMs, by which quercetin significantly reversed the inhibition of M2-TAMS on CRC cell apoptosis and the promotion of M2-TAMS on CRC cell proliferation. Moreover, quercetin could promote the expression of downregulated hsa_circ_0006990 in CRC cells co-cultured with M2-TAMs, and the overexpression of hsa_circ_0006990 significantly reversed the anti-tumour effect of quercetin on CRC. Furthermore, we found quercetin can notably suppress the progression of CRC via mediation of the hsa_circ_0006990/miR-132-3p/MUC13 axis. In conclusion, our results suggested that quercetin inhibits the tumorigenesis of CRC via inhibiting the polarisation of M2 macrophages and downregulating hsa_circ_0006990. Our study provides useful insights for those exploring new methods of treating CRC.

ZEB2, interacting with MDM2, contributes to the dysfuntion of brain microvascular endothelial cells and brain injury after intracerebral hemorrhage.

ZEB2 has been shown to be upregulated in the brain tissues of rats with intracerebral hemorrhage (ICH), but its role in ICH-caused brain injury remains unclear. Here, an ICH rat model was established via intracerebral injection of autologous blood, and the lentivirus-mediated ZEB2 short hairpin RNA (sh-ZEB2) or negative control (scramble) were administered 0.5 hours after ICH. Silencing ZEB2 alleviated ICH-induced neurologic deficits and the increase of BBB permeability, brain water content and ZEB2 expression. Next, OGD (oxygen glucose deprivation) plus hemin was used to treat primary brain microvascular endothelial cells (BMECs) to simulate the ICH condition in vitro. OGD plus hemin upregulated ZEB2 expression and apoptosis, but reduced cell viability, migration, TEER (transendothelial electric resistance) and the expression of vascular-endothelial (VE-) cadherin, occludin and claudin-5, which was reversed by inhibiting ZEB2. Mechanism researches showed that ZEB2 interacted with MDM2 to up-regulate MDM2 protein expression, and then increased E2F1 protein level by suppressing its ubiquitination, which in turn promoted the transcription of ZEB2 to induce its protein expression, so as to enhance the interaction between ZEB2 and MDM2, thereby contributing to OGD plus hemin-induced endothelial dysfunction. Additionally, the joint interference of ZEB2 and MDM2 in vivo had better mitigative effects on ICH-induced brain injury compared with silencing ZEB2 alone. In summary, ZEB2 interacted with MDM2 to promote BMEC dysfunction and brain damage after ICH.

Intestinal dysbacteriosis activates tumor-associated macrophages to promote epithelial-mesenchymal transition of colorectal cancer.

In this study we investigated the association between intestinal dysbacteriosis with colorectal cancer progress and the underlying molecular mechanisms. Tumor progression was evaluated using xenograft mice model. The epithelial-mesenchymal transition (EMT) markers were quantified by both real-time PCR and immunoblotting. The serum content of IL-6 and TNF-α were measured with ELISA kits. Cell proliferation was determined by the Cell Counting Kit-8. Intestinal dysbacteriosis was successfully simulated by the administration of a large dose of antibiotics and was demonstrated to promote xenograft tumor growth and induce EMT. Accordingly, the serum concentrations of cytokines IL-6 and TNF-α were significantly increased. Furthermore, the production and secretion of IL-6 and TNF-α were remarkably elevated in macrophages isolated from intestinal dysbiotic mice in comparison with the normal counterparts, and conditioned medium from these was shown to significantly stimulate EMT process in HT29 cells in vitro. Macrophage depletion completely abrogated the pro-tumor effect of intestinal dysbacteriosis. Our results suggest that intestinal dysbacteriosis stimulates macrophage activation and subsequently induces EMT process via secreted pro-inflammatory cytokines IL-6 and TNF-α.