Autism Spectrum Disorder (ASD) is a severe neurodevelopmental disorder. To enhance the understanding of the gut microbiota structure in ASD children at different ages as well as the relationship ...between gut microbiota and fecal metabolites, we first used the 16S rRNA sequencing to evaluate the gut microbial population in a cohort of 143 children aged 2-13 years old. We found that the α-diversity of ASD group showed no significant change with age, while the TD group showed increased α-diversity with age, which indicates that the compositional development of the gut microbiota in ASD varies at different ages in ways that are not consistent with TD group. Recent studies have shown that chronic constipation is one of the most commonly obvious gastrointestinal (GI) symptoms along with ASD core symptoms. To further investigate the potential interaction effects between ASD and GI symptoms, the 30 C-ASD and their aged-matched TD were picked out to perform metagenomics analysis. We observed that C-ASD group displayed decreased diversity, depletion of species of Sutterella, Prevotella, and Bacteroides as well as dysregulation of associated metabolism activities, which may involve in the pathogenesis of C-ASD. Consistent with metagenomic analysis, liquid chromatography-mass spectrometry (LC/MS) revealed some of the differential metabolites between C-ASD and TD group were involved in the metabolic network of neurotransmitters including serotonin, dopamine, histidine, and GABA. Furthermore, we found these differences in metabolites were associated with altered abundance of specific bacteria. The study suggested possible future modalities for ASD intervention through targeting the specific bacteria associated with neurotransmitter metabolism.
Disturbances of sleep and the underlying circadian rhythm are related to many human diseases, such as obesity, diabetes, cardiovascular disorders, and cognitive impairments. Dysbiosis of the gut ...microbiome has also been reported to be associated with the pathologies of these diseases. Therefore, we proposed that disturbed sleep may regulate gut microbiota homeostasis. In this study, we mimicked the sleep-wake cycle shift, one typical type of circadian rhythm disturbances in young people, in recruited subjects. We used 16S rRNA gene amplicon sequencing to define microbial taxa from their fecal samples. Although the relative abundances of the microbes were not significantly altered, the functional-profile analysis of gut microbiota revealed functions enriched during the sleep-wake cycle shift. In addition, the microbial networks were quite distinct among baseline, shift, and recovery stages. These results suggest that an acute sleep-wake cycle shift may exert a limited influence on the gut microbiome, mainly including the functional profiles of the microbes and the microbial relationships within the microbial community.
Circadian rhythm misalignment due to social jet lag, shift work, early morning starts, and delayed bedtimes is becoming common in our modern society. Disturbances of sleep and the underlying circadian rhythms are related to multiple human diseases, such as obesity, diabetes, cardiovascular disorders, and cognitive impairments. Given the crucial role of microbiota in the same pathologies as are caused by sleep disturbance, how the gut microbiota is affected by sleep is of increasing interest. The results of this study indicate that the acute circadian rhythm disturbance caused by sleep-wake shifts affect the human gut microbiota, especially the functional profiles of gut microbes and interactions among them. Further experiments with a longer-time-scale intervention and larger sample size are needed to assess the effects of chronic circadian rhythm disruption on the gut microbiome and to guide possible microbial therapies for clinical intervention in the related diseases.
The genetic variations and dysbiosis of gut microbiota are associated with ASD. However, the role of the microbiota in the etiology of ASD in terms of host genetic susceptibility remains unclear. ...This study aims to systematically explore the interplay between host genetic variation and gut microbiota in ASD children. Whole-exon sequencing was applied to 26 ASD children and 26 matched controls to identify the single nucleotide variations (SNVs) in ASD. Our previous study revealed alteration in gut microbiota and disorder of metabolism activity in ASD for this cohort. Systematic bioinformatic analyses were further performed to identify associations between SNVs and gut microbiota, as well as their metabolites. The ASD SNVs were significantly enriched in genes associated with innate immune response, protein glycosylation process, and retrograde axonal transport. These SNVs were also correlated with the microbiome composition and a broad aspect of microbial functions, especially metabolism. Additionally, the abundance of metabolites involved in the metabolic network of neurotransmitters was inferred to be causally related to specific SNVs and microbes. Furthermore, our data suggested that the interaction of host genetics and gut microbes may play a crucial role in the immune and metabolism homeostasis of ASD. This study may provide valuable clues to investigate the interaction of host genetic variations and gut microbiota in the pathogenesis of ASD.
The genetic variations and dysbiosis of gut microbiota are associated with ASD. However, the role of the microbiota in the etiology of ASD in terms of host genetic susceptibility remains unclear. ...This study aims to systematically explore the interplay between host genetic variation and gut microbiota in ASD children. Whole-exon sequencing was applied to 26 ASD children and 26 matched controls to identify the single nucleotide variations (SNVs) in ASD. Our previous study revealed alteration in gut microbiota and disorder of metabolism activity in ASD for this cohort. Systematic bioinformatic analyses were further performed to identify associations between SNVs and gut microbiota, as well as their metabolites. The ASD SNVs were significantly enriched in genes associated with innate immune response, protein glycosylation process, and retrograde axonal transport. These SNVs were also correlated with the microbiome composition and a broad aspect of microbial functions, especially metabolism. Additionally, the abundance of metabolites involved in the metabolic network of neurotransmitters was inferred to be causally related to specific SNVs and microbes. Furthermore, our data suggested that the interaction of host genetics and gut microbes may play a crucial role in the immune and metabolism homeostasis of ASD. This study may provide valuable clues to investigate the interaction of host genetic variations and gut microbiota in the pathogenesis of ASD.
Autophagy is a key catabolic process, in which cytosolic cargo is engulfed by the formation of a double membrane and then degraded through the fusing of autophagosomes with lysosomes. Autophagy is a ...constitutively active, evolutionarily conserved, catabolic process important for the maintenance of homeostasis in cellular stress responses and cell survival. Although the mechanisms of autophagy have not yet been fully elucidated, emerging evidence suggests that it plays a dual role in breast cancer and in maintaining the activity of breast cancer stem cells (CSCs). However, it may play a complex role in breast CSC therapy. Breast CSCs, a population of cells with the ability to self-renew, differentiate, and initiate and sustain tumor growth, play an essential role in cancer recurrence, anticancer resistance and metastasis. In addition, the elucidation of the association between autophagy and apoptosis in the tumor context is crucial in order to better address appropriate therapy strategies. In the present review, a summary of the mechanisms and roles of autophagy in breast cancer and CSCs is presented. The potential value of such autophagy modulators in the development of novel breast cancer therapies is discussed.
Recent studies have indicated that deubiquitinating enzymes (DUBs) are related to the stem-cell pathway network and chemo-resistance in cancer. Ubiquitin-specific peptidase 37 (USP37), a novel DUB, ...was identified to be a potential factor associated with tumor progression. However, the biological functions of USP37 in breast cancer remain unclear.
The distribution of USP37 expression in breast cancer and the correlation between USP37 expression and the overall survival rate were detected by The Cancer Genome Atlas (TCGA) database. Gene set enrichment analysis (GSEA) was utilized to evaluate potential mechanism of USP37 in breast cancer. The USP37 expression in breast cancer tissues and breast cancer cell lines were detected by immunohistochemistry and western blotting. Sorting of breast cancer stem cells (BCSCs) were by using MACS assay. In vitro and in vivo assays were performed to examine the biological functions of USP37 in breast cancer cells. MG132, CHX chase, immunofluorescence staining and co-immunoprecipitation assays were used to test the interaction between USP37 and Gli-1.
Bioinformatics analysis demonstrated that USP37 gene was elevated in breast cancer tissues and its overexpression was strongly correlated with the increased mortality rate. GSEA analysis showed that USP37 expression was positively associated with cell growth and metastasis while negatively related to cell apoptosis in the TCGA breast cancer samples. USP37 expression was elevated in breast cancer tissues and breast cancer cell lines. Moreover, we also detected that USP37 was overexpressed in BCSCs. USP37 regulated the ability of cell invasion, epithelial-mesenchymal transition (EMT), stemness and cisplatin sensitivity in breast cancer cell lines. Additionally, USP37 knockdown inhibited tumorigenicity and increased anticancer effect of cisplatin in vivo. Knockdown of USP37 significantly decreased hedgehog (Hh) pathway components Smo and Gli-1. Gli-1 was stabilized by USP37 and they interacted with each other. Further studies indicated that USP37 knockdown could inhibit the stemness, cell invasion and EMT in breast cancer via downregulation of Hh pathway.
These findings reveal that USP37 is highly expressed in BCSCs and is correlated with poor prognosis in breast cancer patients. USP37 can regulate the stemness, cell invasion and EMT via Hh pathway, and decreased USP37 confers sensitivity to cisplatin in breast cancer cells. USP37 is required for the regulation of breast cancer progression, as well as a critical target for clinical treatment of breast cancer.
ARE THERE DIGITAL TECH BUBBLES IN CHINA? Qin, Meng; Su, Chi-Wei; Qiu, Lianhong ...
Technological and economic development of economy,
01/2024, Letnik:
30, Številka:
3
Journal Article
Recenzirano
Odprti dostop
This exploration employs the generalized supremum augmented Dickey-Fuller (GSADF) approach to explore whether there are digital tech bubbles in China. The empirical results suggest the existence of ...multiple digital tech bubbles, which are mostly accompanied by an excessive rise. However, the appearance of digital tech bubbles is curbed since 2016, mainly due to the increasing mature regulations in relevant fields. Besides, bubbles in different digital technologies are similar during the same period, which could be attributed to the close relationships among them. Additionally, we further investigate the factors influencing the explosive behaviours, and find that the Chinese stock market positively affects digital tech bubbles, while economic policy uncertainties and situations negatively influence such explosive behaviors. In the context of the new round of scientific and technological revolution and industrial transformation, these conclusions provide valuable implications to achieve the target of constructing a “Digital China” by becoming moderately cautious about potential bubbles in the digital tech industry.
SEE PDF Correction Open Access Published:09 August 2023 Correction: PTENP1/miR-20a/PTEN axis contributes to breast cancer progression by regulating PTEN via PI3K/AKT pathway Xue Gao1,2, Tao Qin1, Jun ...Mao1,3,4, Jun Zhang5, Shujun Fan1, Ying Lu3,4, Zhigang Sun2, Qingqing Zhang1, Bo Song1 & … Fig. 3 figure 1 Low PTENP1 level enhances the malignant behavior of BC cells. a The viability of transfected BC cells were detected by CCK8 assays at 0, 24, 48,72, 96 h. b Knockdown of PTENP1 enhanced the colony formation in BC cells. c The proliferation of siPTENP1 transfected cells was increased by Edu staining (Scale bar = 20 μm). d Ki67 staining also showed intensive proliferation (Scale bar = 20 μm). e The aggressiveness was enhanced with knocking down PTENP1 in MCF-7 cells (Scale bar = 20 μm). f The siPTENP1-MCF-7 cells revealed more resistance to ADR. g Higher IC50 value was also proved the enhanced chemoresistance to ADR. h Weakened colony formation ability was shown in response to ADR. i More resistance to ADR was shown in siPTENP1-MCF-7 cells. Data are the means ± SD of triplicate determinants (*P < 0.05) (Scale bar = 200 μm) Full size image Fig. 6 figure 2 Inhibition of miR-20a reverses the promotional effect of siPTENP1 by mediating PTEN expression in BC progression. a PTEN mRNA expression was identified with the treatment of miR-20a inhibitor or siPTENP1. b PTEN protein level was detected by western blot. c The proliferation was measured by CCK8 assays. d Colony formation assay was used to measure the colony formation of transfected cells. e The aggressiveness was determined by transwell assay (Scale bar = 20 μm). f CCK8 assays were carried out to assess the chemoresistance to ADR with different treated BC cells. g IC50 values were calculated in differential treated MCF-7 cells. h In response to ADR, the colony formation was measured in transfected MCF-7 cells. i The AnnexinV and PI staining was used to determine the occurrence of apoptosis.
Protein tyrosine phosphatase receptor type D (PTPRD) is a tumor suppressor gene that is epigenetically silenced and mutated in several cancers, including breast cancer. Since IL-6/STAT3 signaling is ...often hyperactivated in breast cancer and STAT3 is a direct PTPRD substrate, we investigated the role of PTPRD in breast cancer and the association between PTPRD and IL-6/STAT3 signaling. We found that PTPRD acts as a tumor suppressor in breast cancer tissues and that high PTPRD expression is positively associated with tumor size, lymph node metastasis, PCNA expression, and patient survival. Moreover, breast cancers with high PTPRD expression tend to exhibit high IL-6 and low phosphorylated-STAT3 expression. IL-6 was found to inhibit miR-34a transcription and induce PTPRD expression in breast cancer and breast epithelial cells, whereas PTPRD was shown to mediate activated STAT3 dephosphorylation and to be a conserved, direct target of miR-34a. IL-6-induced PTPRD upregulation was blocked by miR-34a mimics, whereas experimental PTPRD overexpression suppressed MDA-MB-231 cell migration, invasion, and epithelial to mesenchymal transition, decreased STAT3 phosphorylation, and increased miR-34a transcription. Our findings suggest that PTPRD mediates activated STAT3 dephosphorylation and is induced by the IL-6/STAT3-mediated transcriptional inhibition of miR-34a, thereby establishing a negative feedback loop that inhibits IL-6/STAT3 signaling overactivation.
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