The functional role of respiratory microbiota has attracted an accumulating attention recently. However, the role of respiratory microbiome in lung carcinogenesis is mostly unknown. Our study aimed to characterize and compare bilateral lower airway microbiome of lung cancer patients with unilateral lobar masses and control subjects. Protected bronchial specimen brushing samples were collected from 24 lung cancer patients with unilateral lobar masses (paired samples from cancerous site and the contralateral noncancerous site) and 18 healthy controls undergoing bronchoscopies and further analyzed by 16S rRNA amplicon sequencing. As results, significant decreases in microbial diversity were observed in patients with lung cancer in comparison to the controls, alpha diversity steadily declined from healthy site to noncancerous to cancerous site. Genus Streptococcus was significantly more abundant in cancer cases than the controls, while Staphylococcus was more abundant in the controls. The area under the curve of genus Streptococcus used to predict lung cancer was 0.693 (sensitivity = 87.5%, specificity = 55.6%). The abundance of genus Streptococcus and Neisseria displayed an increasing trend whereas Staphylococcus and Dialister gradually declined from healthy to noncancerous to cancerous site. Collectively, lung cancer-associated microbiota profile is distinct from that found in healthy controls, and the altered cancer-associated microbiota is not restricted to tumor tissue. The genus Streptococcus was abundant in lung cancer patients and exhibited moderate classification potential. The gradual microbiota profile shift from healthy site to noncancerous to paired cancerous site suggested a change of the microenvironment associated with the development of lung cancer.

Peptidoglycan recognition proteins (PGRPs) and commensal microbes mediate pathogen infection outcomes in insect disease vectors. Although PGRP-LD is retained in multiple vectors, its role in host defense remains elusive. Here we report that Anopheles stephensi PGRP-LD protects the vector from malaria parasite infection by regulating gut homeostasis. Specifically, knock down of PGRP-LD (dsLD) increased susceptibility to Plasmodium berghei infection, decreased the abundance of gut microbiota and changed their spatial distribution. This outcome resulted from a change in the structural integrity of the peritrophic matrix (PM), which is a chitinous and proteinaceous barrier that lines the midgut lumen. Reduction of microbiota in dsLD mosquitoes due to the upregulation of immune effectors led to dysregulation of PM genes and PM fragmentation. Elimination of gut microbiota in antibiotic treated mosquitoes (Abx) led to PM loss and increased vectorial competence. Recolonization of Abx mosquitoes with indigenous Enterobacter sp. restored PM integrity and decreased mosquito vectorial capacity. Silencing PGRP-LD in mosquitoes without PM didn’t influence their vector competence. Our results indicate that PGPR-LD protects the gut microbiota by preventing hyper-immunity, which in turn promotes PM structurally integrity. The intact PM plays a key role in limiting P. berghei infection.

Esophageal squamous cell carcinoma (ESCC) is one of the most common types of cancer and the leading causes of cancer-related mortality worldwide, especially in Eastern Asia. Here, we downloaded the microarray data of lncRNA expression profiles of ESCC patients from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) data sets and divided into training, validation and test set. The random survival forest (RSF) algorithm and Cox regression analysis were applied to identify a seven-lncRNA signature. Then the predictive ability of the seven-lncRNA signature was evaluated in the validation and test set using Kaplan-Meier test, time-dependent receiver operating characteristic (ROC) curves and dynamic area under curve (AUC). Stratified analysis and multivariate Cox regression also demonstrated the independence of the signature in prognosis prediction from other clinical factors. Besides, the predict accuracy of lncRNA signature was much better than that of tumor-node-metastasis (TNM) stage in all the three sets. LncRNA combined with TNM displayed better prognostic predict ability than either alone. The role of LINC00173 from the signature in modulating the proliferation and cell cycle of ESCC cells was also observed. These results indicated that this seven-lncRNA signature could be used as an independent prognostic biomarker for prognosis prediction of patients with ESCC.

Background In cancer progression, hypoxia, or low oxygen tension, is a major regulator of tumor aggressiveness and metastasis. However, how cancer cells adapt to the hypoxia and communicate with other mesenchymal cells in microenvironment during tumor development remains to be elucidated. Here, we investigated the involvement of exosomes in modulating angiogenesis and enhancing metastasis in esophageal squamous cell carcinoma (ESCC). Methods Differential centrifugation, transmission electron microscopy and nanoparticle tracking analysis were used to isolate and characterize exosomes. Colony formation and transwell assay were performed to assess the proliferation, migration and invasion of human umbilical vein endothelial cells (HUVECs). The tube formation assay and matrigel plug assay were used to evaluate the vascular formation ability of HUVECs in vitro and in vivo respectively. An in vivo nude mice model was established to detect the regulatory role of exosomes in ESCC progression. Microarray analysis was performed to analyze the transcriptome profiles in HUVECs. Results Exosomes derived from ESCC cells cultured under hypoxia played a better role in promoting proliferation, migration, invasion and tube formation of HUVECs in vitro and in vivo than exosomes from ESCC cells cultured under normoxia. Moreover, hypoxic exosomes significantly enhanced the tumor growth and lung metastasis compared with normoxic exosomes in nude mice models. Interestingly, endothelial cells were programmed by hypoxic and normoxic exosomes from ESCC cells which altered the transcriptome profile of HUVECs. Conclusions Taken together, our data identified an angiogenic role of exosomes from ESCC cells which shed light on the further application of exosomes as valuable therapeutic target for ESCC. Electronic supplementary material The online version of this article (10.1186/s13046-019-1384-8) contains supplementary material, which is available to authorized users.

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The Liverbase ( http://liverbase.hupo.org.cn ) integrates information on the human liver proteome, including the function, abundance, and subcellular localization of proteins as well as associated disease information. The overall objective of the Liverbase is to provide a unique public resource for the liver community by providing comprehensive functional annotation of proteins implicated in liver development and disease. The central database features are manually annotated proteins localized in or functionally associated with human liver. In this first version of Liverbase, the associated data includes the human liver proteome (6788 proteins) and transcriptome (11205 significantly expressed genes: 10224 from CHIP and 5422 from MPSS, respecively) from the Chinese human liver proteome project (CNHLPP). As a database made publicly available through the Web site, Liverbase provides browsing and searching capabilities and a compilation of external links to other databases and homepages. Liverbase enables (i) the establishment of liver GO slim with 51 nonredundant items; (ii) systematic searches for proteins within specific functional or metabolic pathways; (iii) systematic searches that aim to find the proteins that underlie common and rare liver diseases; and (iv) the integration of detailed protein annotations derived from the literature. Liverbase also contains an external links page with links to other biological databases and homepages, including GO, KEGG, pfam, SWISS-PROT, and GNF databases. Liverbase users can utilize all these information to conduct systems biology research on liver.

Icariin is the major active ingredient in Herba epimedii which is a commonly used Chinese herbal medicine for the treatment of osteoporosis. The present study aims to evaluate the osteoprotective effect of Icariin in glucocorticoid-induced osteoporosis in vivo and investigate the effect of Icariin on glucocorticoid-induced osteocyte apoptosis in vitro. A total of 48 female Sprague-Dawley rats were used. Glucocorticoid-induced osteoporosis was induced by daily injections of dexamethasone (0.1 mg/kg, daily, s.c.) for 60 days, whereas sham animals were injected daily with vehicle. At the end of the osteoporosis development period, osteoporotic rats were randomized to receive: vehicle (n = 8), Icariin (5,125 mg/kg, i.g.; n = 8), or alendronate (0.03 mg/kg, s.c.; n = 8) for 12 weeks. Sham animals were treated with vehicle for 12 weeks. At the beginning and at the end of treatments, animals were examined for bone mineral density. Serum bone-alkaline phosphatase and carboxy-terminal collagen cross links were measured. Primary osteocytes were isolated, and apoptosis was determined by trypan-blue assay. Interaction between Icariin and estrogen receptor and prosurvival signaling pathways activated by Icariin were also investigated. Icariin showed a comparable efficacy with alendronate in increasing bone mass. Icariin significantly increased bone-alkaline phosphatase (bone formation marker) and reduced carboxy-terminal collagen cross links (bone resorption marker). In vitro studies demonstrated that Icariin significantly prevented GC-induced apoptosis in osteocytes by activating ERK signaling via estrogen receptor. Our results suggest that Icariin might exert osteoprotective effect by maintaining osteocyte viability, thereby, regulating bone remodeling. Furthermore, our study provides preclinical evidence for the efficacy of Icariin for management of Glucocorticoid-induced osteoporosis.

) is reported to be overexpressed in colorectal carcinoma (CRC), but the role of miR-191 in CRC progress remained unclear. This study demonstrated that High miR-191 expression was associated with clinical stage, lymph node metastasis, liver metastasis and depth of tumor invasion. Kaplan-Meier analysis indicated that patients with high miR-191 expression had a poor overall survival. Moreover, multivariate analysis showed that miR-191 was an independent prognostic factor in patients with CRC. Furthermore, we found that tissue inhibitor of metalloprotease 3 (TIMP3) was a direct target of miR-191 in colorectal cancer SW620 cells. TIMP3 downregulation mediated by miR-191 activated matrix metalloproteinases (MMPs) and thus promoted invasiveness of cancer cells. Anti-miR-191 could attenuate the invasiveness, suppress proliferation and induce apoptosis by restoring TIMP3 expression. Our results suggested that miR-191 might be a potential diagnostic and therapeutic target in patients with colorectal cancer.