Biology subjects

Zi, J.

Publications and source records attributed to Zi, J..

8 recordsLinked to original sources

bioRxiv2022

SMAD4 suppresses colitis-associated carcinoma through inhibition of CCL20/CCR6-mediated inflammation

Background & AimsChronic inflammation in the colon is a predisposing factor for colon cancer. We previously reported that colon epithelial cell silencing of Smad4, the central downstream mediator of TGF{beta} family signaling, increased epithelial expression of inflammatory genes, including the chemokine CCL20, and increased susceptibility to colitis-associated cancer. Here, we examine the role of the chemokine/receptor pair CCL20/CCR6 in mediating colitis-associated colon carcinogenesis induced by SMAD4 loss. MethodsMice with conditional, epithelial-specific Smad4 loss with and without germline deletion of the Ccr6 gene were subjected to three rounds of dextran sodium sulfate and followed for up to 3 months. Tumors were quantified histologically, and immune cell populations were analyzed by flow cytometry and immunostaining. ResultsIn humans, SMAD4 expression inversely correlated with CCL20 expression. Smad4 loss in mouse colon epithelium led to enlarged gut-associated lymphoid tissues and recruitment of specific immune cell subsets to the mouse colon epithelium and underlying stroma, particularly Treg, Th17, and dendritic cells. Loss of CCR6 abrogated these immune responses and significantly reduced the incidence of colitis-associated tumors observed with loss of SMAD4 alone. ConclusionsRegulation of mucosal inflammation is a critical role of SMAD4 signaling within the colon epithelium and central to its tumor suppressor function in the colon. A key downstream node in this regulation is suppression of CCL20 signaling by the epithelium to CCR6 in immune cells. Loss of SMAD4 in the colon epithelium increases CCL20 expression and chemoattraction of CCR6+ immune cells, contributing to greater susceptibility to colon cancer.

cancer biology↗

bioRxiv2020

Proteomics study of colorectal cancer and adenomatous polyps identifies TFR1, SAHH, and HV307 as potential biomarkers for screening

Colorectal cancer (CRC) is a malignant tumour with high morbidity and mortality worldwide. Efficient screening strategies for CRC and pre-cancerous lesions will promote early medical intervention and treatment, thus reducing morbidity and mortality. Proteins are generally considered key biomarkers of cancer. Herein, we performed a quantitative, tissue-original proteomics study in a cohort of ninety patients from pre-cancerous to cancerous conditions by liquid chromatography-tandem mass spectrometry. A total of 134,812 peptides, 8,697 proteins, 2,355 (27.08%) union differentially expressed proteins (DEPs), and 409 shared DEPs (compared with adjacent tissues) were identified. The number of DEPs showed a positive correlation with increasing severity of illness. The union and shared DEPs were both enriched in the KEGG pathway of focal adhesion, metabolism of xenobiotics by cytochrome P450, and drug metabolism - cytochrome P450. Among the 2,355 union DEPs, 32 were selected for identification and validation by multiple reaction monitoring from twenty plasma specimens. Of these, three proteins, transferrin receptor protein 1 (TFR1), adenosylhomocysteinase (SAHH), and immunoglobulin heavy variable 3-7 (HV307), were significantly differentially expressed and displayed the same expression pattern in plasma as observed in the tissue data. In conclusion, TFR1, SAHH, and HV307 may be considered as potential biomarkers for screening of CRC. SignificanceCRC is a malignant tumour with high morbidity and mortality worldwide. Efficient screening strategies for CRC and pre-cancerous lesions can play an important role in addressing the issue of high morbidity and mortality. Screening of molecular biomarkers provide a non-invasive, cost-effective and effective approach. Proteins are generally considered key molecular biomarkers of cancer. Our study reports a quantitative proteomics analysis of protein biomarkers for colorectal cancer (CRC) and adenomatous polyps and identifies TFR1, SAHH, and HV307 as potential biomarkers for screening. The research makes a significant contribution to the literature because whereas mass spectrometry-based proteomics research has been widely used for clinical research, its application to clinical translation is lacking as parallel specimens ranging from pre-cancerous to cancerous tissues, according to the degree of disease progression, have not been readily assessed.

biochemistry↗

bioRxiv2020

Inter-determination of blood metabolite levels and gut microbiome supported by Mendelian randomization

The gut microbiome has been implicated in a variety of physiological states, but controversy over causality remains unresolved. Here, we performed bidirectional Mendelian randomization (MR) analyses on 3,432 Chinese individuals with whole genome, whole metagenome, anthropometric, and blood metabolic trait data. We identified 58 causal relationships between the gut microbiome and blood metabolites, and replicated 43 of them. Increased relative abundances of fecal Oscillibacter and Alistipes were causally linked to decreased triglyceride concentration. Conversely, blood metabolites such as glutamic acid appeared to decrease fecal Oxalobacter, and members of Proteobacteria were influenced by metabolites such as 5-methyltetrahydrofolic acid, alanine, glutamate, and selenium. Two-sample MR with data from Biobank Japan partly corroborated results with triglyceride and with uric acid, and also provided causal support for published fecal bacterial markers for cancer and cardiovascular diseases. This study illustrates the value of human genetic information to help prioritize gut microbial features for mechanistic and clinical studies.

genetics↗

bioRxiv2020

Prediction of meiosis-essential genes based upon the dynamic proteomes responsive to spermatogenesis

Mammalian meiosis is a specific cell division process during sexual reproduction, whereas a comprehensive proteome of the different meiotic stages has not been systematically investigated. Here, we isolated different types of spermatocytes from the testes of spermatogenesis-synchronized mice and quantified the corresponding proteomes with high-resolution mass spectrometry. A total of 8,002 proteins were identified in nine types of germ cells, and the protein signatures of spermatogenesis were characterized using the dynamic proteomes. A supervised machine learning package, FuncProFinder, was developed to predict meiosis-essential candidate genes based on changes in their protein abundance. Of the candidates without functional annotation, four of the ten genes with the highest prediction scores, Zcwpw1, Tesmin, 1700102P08Rik, and Kctd19, were validated as meiosis-essential genes using knockout mouse models. The proteomic analysis of spermatogenic cells provides a solid foundation for studying the mechanism of mammalian meiosis.

developmental biology↗

bioRxiv2019

Protein profiling reveals the characteristic changes of complement cascade pathway in the tissues of gastric signet ring cell carcinoma

Signet ring cell carcinoma (SRCC) is a histological subtype of gastric cancer that has distinct features in cellular morphology, epidemiology and clinicopathology compared with adenocarcinomas (ACs). Lacking of systematically molecular overview to this disease made a slow progress in diagnosis and therapy for SRCC. In the present proteomics study, the gastric tissues were collected from tumor and adjacent regions including 14 SRCC and 34 AC cases, and laser capture microdissection (LCM) was employed to eradicate cellular heterogeneity of the tissues. Over 6,000 proteins were quantified through data independent acquisition (DIA) mass spectrometry (MS). The quantitative profiles of proteomes in tumor tissues, either AC or SRCC, were dramatically different from that in the corresponding adjacencies, whereas the SRCC proteomes appeared not distinguishable to the AC proteomes via hierarchical clustering. However, focusing on univariate analysis and pathway enrichment unrevealed that some proteins and pathways bared the differences between SRCC and ACs. Importantly, the abundance changes for a bulk of proteins involved in complement cascade were highly associated with SRCC but not so sensitive to the AC status. A hypothesis, therefore, was proposed that the complement cascade was evoked in the SRCC microenvironment upon infiltration, while the SRCC cells survived from the complement cytotoxicity by secreting negative regulators. Moreover, an attempt was made to seek appropriate cell model for gastric SRCC, through proteomic comparison of the 15 gastric cell lines and the gastric tumors. The prediction upon supervised classifier suggested none of these gastric cell lines qualified in mimic to SRCC.

cell biology↗

bioRxiv2019

Distinct gut metagenomics and metaproteomics signatures in prediabetics and treatment-naïve type 2 diabetics

BackgroundThe gut microbiota plays important roles in modulating host metabolism. Previous studies have demonstrated differences in the gut microbiome of T2D and prediabetic individuals compared to healthy individuals, with distinct disease-related microbial profiles being reported in groups of different age and ethnicity. However, confounding factors such as anti-diabetic medication hamper identification of the gut microbial changes in disease development.\n\nMethodWe used a combination of in-depth metagenomics and metaproteomics analyses of faecal samples from treatment-naive type 2 diabetic (TN-T2D, n=77), pre-diabetic (Pre-DM, n=80), and normal glucose tolerant (NGT, n=97) individuals to investigate compositional and functional changes of the gut microbiota and the faecal content of microbial and host proteins in Pre-DM and treatment-naive T2D individuals to elucidate possible host-microbial interplays characterising different disease stages.\n\nFindingsWe observed distinct differences characterizing the gut microbiota of these three groups and validated several key features in an independent TN-T2D cohort. We also demonstrated that the content of several human antimicrobial peptides and pancreatic enzymes differed in faecal samples between three groups, such as reduced faecal level of antimicrobial peptides and pancreatic enzymes in TN-T2D.\n\nInterpretationOur findings suggest a complex, disease stage-dependent interplay between the gut microbiota and the host and emphasize the value of metaproteomics to gain further insight into interplays between the gut microbiota and the host.\n\nFundingNational Key Research and Development Program of China, No. 2017YFC0909703, Shenzhen Municipal Government of China, No. JCYJ20170817145809215, and National Natural Science Foundation of China, No. 31601073.

microbiology↗

bioRxiv2019

A multi-omic cohort as a reference point for promoting a healthy human gut microbiome

More than a decade of gut microbiome studies have a common goal for human health. As most of the disease studies sample the elderly or the middle-aged, a reference cohort for young individuals has been lacking. It is also not clear what other omics data need to be measured to better understand the gut microbiome. Here we present high-depth metagenomic shotgun sequencing data for the fecal microbiome together with other omics data in a cohort of 2,183 adults, and observe a number of vitamins, hormones, amino acids and trace elements to correlate with the gut microbiome and cluster with T cell receptors. Associations with physical fitness, sleeping habits and dairy consumption are identified in this large multi-omic cohort. Many of the associations are validated in an additional cohort of 1,404 individuals. Our comprehensive data are poised to advise future study designs to better understand and manage our gut microbiome both in population and in mechanistic investigations.

microbiology↗

bioRxiv2019

The vagino-cervical microbiome as a woman's life history

The gut microbiome has been the center of attention for human commensal microbiome studies. The vaginal microbiome is also densely populated with bacteria, viruses and fungi, and the presence of microorganisms beyond the cervix is increasingly reported in non-infectious conditions1-3. Due to the over 90% of human sequences in female reproductive tract samples3,4, metagenomic information has been very limited. 16S rRNA gene amplicon sequencing studies have identified community types in the vaginal microbiota, and observed its dynamic changes due to menstrual cycles and sexual behaviors in small cohorts5,6. Here we perform metagenomic shotgun sequencing on cervical samples from 516 women of reproductive age (more than 10-fold of the Human Microbiome Project (HMP)4), and dissect major factors, especially pregnancy and delivery histories and contraception methods on the microbiome composition. Features of other body sites, such as mood fluctuations and facial speckles could potentially be deduced from the vagino-cervical microbiome. Our results offer an unprecedented glimpse into the microbiota in the female reproductive tract and imply disease susceptibilities that may be relieved by behavioural changes.

microbiology↗