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There is increasing evidence suggest a link between allergic rhinitis (AR) and psychiatric disorders. However, casual associations between these variables remain uncertain. We performed bi-directional two-sample Mendelian Randomization (MR) to examine the causality association of AR with 11 different psychiatric disorders or relevant traits. MR was conducted using the inverse-variance weighted method (IVW), MR-Egger and weighted median methods. Sensitivity analyses included the MR-Egger regression and MR pleiotropy residual sum and outlier test. AR from 2 different GWAS data was positively associated with bipolar disorder (OR=1.649, 95% CI: 1.077-2.526; P=0.021; OR=1.599; 95%CI 1.058-2.417; P=0.026) and major depressive disorder (OR=1.539; 95%CI 1.007-2.353; P=0.047), but not other psychiatric illnesses. Bidirectional analyses showed that bipolar disorder is negatively associated with AR (OR=0.964; 95%CI: 0.936-0.993; P=0.015). There was no evidence for potential causal schizophrenia and effects of attention deficit/hyperactivity disorder on risk of AR by MR method, but MR pleiotropy residual outlier test suggested that attention deficit/hyperactivity disorder is negatively associated with AR after outlier correction (OR=0.976, 95%CI: 0.958-0.995, P=0.012). This MR study indicated that AR was a causal risk factor for bipolar disorder and major depressive disorder, but not for other psychiatric disorders. Bipolar disorder and attention deficit/hyperactivity disorder may be a protective factor for AR. Further studies could be carried out to unravel the underlying mechanism in AR and psychiatric disorders.

Inflammatory bowel disease (IBD) remains a severe disease for most patients, with its incidence and prevalence increasingly globally. Currently, there is no effective treatments for IBD, and traditional treatments have multiple side effects. Therefore, novel therapeutic strategies or alternative drugs are urgently needed. Previous studies have shown that mesenchymal stem cell-derived exosomes have exhibited promising therapeutic effects on inflammatory disease. Here, we performed intravenous injection of human adipose mesenchymal stem cell (hADSC)-derived exosomes (hADSC-Exo) in a DSS-induced IBD mouse model and found that hADSC-Exo promoted functional recovery, downregulated inflammatory responses, reduced intestine cell apoptosis, increased epithelial regeneration and maintained intestinal barrier integrity. Moreover, we established a colon organoid, hADSC-Exo and TNF-α co-cultured system to explore the protective effect of hADSC-Exo on integrity of intestine mucosa and epithelial regeneration. We showed that hADSC-Exo not only can promote the proliferation and regeneration of Lgr5+ ISCs and epithelial cells but also ameliorate the inflammation damage in TNF-α induced inflammatory damaged mice colon organoids. Taken together, our findings indicate that hADSC-Exo protects intestine integrity, activates intestine epithelial cell and ISCs proliferation, suggesting that hADSC-Exo might be a potential effective treatment approach for IBD. We also provide a theoretical basis for new therapeutic strategies for cell-free therapy in inflammatory bowel disease.

Mesenchymal stem cells (MSCs) have beneficial effects on wound healing. MSCs function through direct cell-cell communication or indirectly through paracrine secretion of exosomes. Here, we found that MSC-derived exosomes had pro-wound healing effects via promotion of angiogenesis; however, this promoting effect was significantly reduced when senescence was induced in parental MSCs by hydrogen peroxide (H2O2). Further experiments showed that decreased miR-146a expression in exosomes derived from senescent MSCs (s-exo) contributed to these findings. In vitro, the pro-angiogenic effect of s-exo on tube formation in human umbilical vein endothelial cells was significantly reduced compared with that of exosomes derived from control MSCs (c-exo). In vivo, higher tube numbers and longer tube lengths were observed in the c-exo group compared with the s-exo group. Using microarray analysis, we found that miR-146a level in s-exo was lower than that in c-exo. Knockdown of miR-146a in c-exo decreased its capacity to promote angiogenesis, and overexpression of miR-146a in s-exo partially rescued its impaired pro-angiogenic capacity, thereby confirming that downregulation of miR-146a contributed to the reduced pro-wound healing capacity of s-exo. Our study is the first to demonstrate that cell senescence induced by H2O2 alters the pro-angiogenic ability of exosomes by modulating the expression of exosomal miRNAs, especially miR-146a, thus providing new insights into the correlation between parental cell state and exosome content and function.

Background The initiation and progression of hepatocellular carcinoma (HCC) are largely dependent on its local microenvironment. Adipocytes are an important component of hepatic microenvironment in nonalcoholic fatty liver disease (NAFLD), which is a significant risk factor for HCC. Given the global prevalence of NAFLD, a better understanding of the interplay between HCC cells and adipocytes is urgently needed. Exosomes, released by malignant cells, represent a novel way of cell-cell interaction and have been shown to play an important role in cancer cell communication with their microenvironment. Here, we explore the role of HCC-derived exosomes in the cellular and molecular conversion of adipocytes into tumor-promoting cells. Methods Exosomes were isolated from HCC cell line HepG2 and added to adipocytes. Transcriptomic alterations of exosome-stimulated adipocytes were analyzed using gene expression profiling, and secretion of inflammation-associated cytokines was detected by RT-PCR and ELISA. In vivo mouse xenograft model was used to evaluate the growth-promoting and angiogenesis-enhancing effects of exosome-treated adipocytes. Protein content of tumor exosomes was analyzed by mass spectrometry. Activated phospho-kinases involved in exosome-treated adipocytes were detected by phospho-kinase antibody array and Western blot. Results Our results demonstrated that HCC cell HepG2-derived exosomes could be actively internalized by adipocytes and caused significant transcriptomic alterations and in particular induced an inflammatory phenotype in adipocytes. The tumor exosome-treated adipocytes, named exo-adipocytes, promoted tumor growth, enhanced angiogenesis, and recruited more macrophages in mouse xenograft model. In vitro, conditioned medium from exo-adipocytes promoted HepG2 cell migration and increased tube formation of human umbilical vein endothelial cells (HUVECs). Mechanistically, we found HepG2 exosomes activated several phopho-kinases and NF-κB signaling pathway in exo-adipocytes. Additionally, a total of 1428 proteins were identified in HepG2 exosomes by mass spectrometry. Conclusions Our results provide new insights into the concept that tumor cell-derived exosomes can educate surrounding adipocytes to create a favorable microenvironment for tumor progression.

A key feature of cancer cachexia is the loss of adipose tissue, mainly due to increased lipolysis and an impairment of adipogenesis. Recent findings have shown that cancer exosomes promoted lipolysis in adipose tissue. However, effects of cancer exosomes on adipogenesis were not reported. In this study, we found that lung cancer exosomes could be internalized by human adipose tissue-derived mesenchymal stem cells (hAD-MSCs) and significantly inhibited hAD-MSC adipogenesis as demonstrated by Oil Red O staining and decreased expression of adipogenic-specific genes. Specifically, TGFβ signaling pathway was demonstrated to be involved in the inhibitive effects of lung cancer exosomes on hAD-MSC adipogenesis. Additionally, TGFβ was detected in A549 exosomes. Herein, this study reports that the effect of lung cancer cell exosomes on hAD-MSC adipogenic differentiation was mediated by TGFβ signaling pathway and suggests the involvement of cancer exosomes in weight loss of cancer cachexia.

Objective Although adipocytes are the most abundant stromal cell component in breast cancer tissues, their interaction with breast cancer cells has been less investigated compared to cancer-associated fibroblasts or macrophages. Exosomes are a novel way of cell-cell communication and have been demonstrated to play an important role in various biological processes. However, to our knowledge, only a few studies have reported the effects of adipocyte exosomes on tumor development. Here, utilizing exosomes isolated from in vitro mesenchymal stromal/stem cell (MSC)-differentiated adipocytes, we systematically investigated this issue in a breast cancer model. Material and methods Exosomes were isolated from MSC-differentiated adipocytes and added to breast cancer cells MCF7. Cell proliferation was detected by MTS, and migration was analyzed by wound healing and transwell assay. An in vivo mouse xenograft model was used to evaluate MSC-differentiated adipocyte exosomes’ contribution to tumor growth. Signaling pathway activation was evaluated by western blot and immunofluorescence staining. Results We found MSC-differentiated adipocyte-derived exosomes are actively incorporated by breast cancer cell MCF7 and subsequently promote MCF7 proliferation and migration as well as protect MCF7 from serum derivation or chemotherapeutic drug-induced apoptosis in vitro. In the in vivo mouse xenograft model, depletion of exosomes reduces tumor-promoting effects of adipocytes. Transcriptomic analysis of MSC-differentiated adipocyte exosome-treated MCF7 identified several activated signaling pathways, among which we confirm the Hippo signaling pathway and found a blockade of this pathway leads to a reduced growth-promoting effect of adipocyte exosomes. Conclusion Taken together, our findings provide new insights into the role of adipocyte exosomes in the tumor microenvironment.