Immune-related Functions Research Articles

Human-specific protein-coding and lncRNA genes cast sex-biased genes in the brain and their relationships with brain diseases

BackgroundGene expression shows sex bias in the brain as it does in other organs. Since female and male humans exhibit noticeable differences in emotions, logical thinking, movement, spatial orientation, and even the incidence of neurological disorders, sex biases in the brain are especially interesting, but how they are determined, whether they are conserved or lineage specific, and what the consequences of the biases are, remain poorly explored and understood.MethodsBased on RNA-seq datasets from 16 and 14 brain regions in humans and macaques across developmental periods and from patients with brain diseases, we used linear mixed models (LMMs) to differentiate variations in gene expression caused by factors of interest and confounding factors and identify four types of sex-biased genes. Effect size and confidence in each effect were measured upon the local false sign rate (LFSR). We utilized the biomaRt R package to acquire orthologous genes in humans and macaques from the BioMart Ensembl website. Transcriptional regulation of sex-biased genes by sex hormones and lncRNAs were analyzed using the CellOracle, GENIE3, and Longtarget programs. Sex-biased genes’ functions were revealed by gene set enrichment analysis using multiple methods.ResultsLineage-specific sex-biased genes greatly determine the distinct sex biases in human and macaque brains. In humans, those encoding proteins contribute directly to immune-related functions, and those encoding lncRNAs intensively regulate the expression of other sex-biased genes, especially genes with immune-related functions. The identified sex-specific differentially expressed genes (ssDEGs) upon gene expression in disease and normal samples also indicate that protein-coding ssDEGs are conserved in humans and macaques but that lncRNA ssDEGs are not conserved. The results answer the above questions, reveal an intrinsic relationship between sex biases in the brain and sex-biased susceptibility to brain diseases, and will help researchers investigate human- and sex-specific ncRNA targets for brain diseases.ConclusionsHuman-specific genes greatly cast sex-biased genes in the brain and their relationships with brain diseases, with protein-coding genes contributing to immune response related functions and lncRNA genes critically regulating sex-biased genes. The high proportions of lineage-specific lncRNAs in mammalian genomes indicate that sex biases may have evolved rapidly in not only the brain but also other organs.

Deciphering the Molecular Landscape of Dengue Infection: Insights from gene expression profiling and Protein Interactions

Dengue fever (DF) is a viral infection recognized as one of the most rapidly spreading vector-borne diseases among humans. However, the molecular mechanisms underlying disease aetiology and potential therapeutic targets remain unclear. This study presents a thorough examination of differentially expressed genes (DEGs) throughout the spectrum of Dengue infection stages, offering insights into disease mechanisms and therapeutic targets. Through meticulous analysis of DEGs within each infection stage, key genes pertinent to disease progression are identified, highlighting their roles in host-virus interactions. Noteworthy discoveries include the upregulation of IFI27 and USP18 in mild infection, suggesting involvement in viral replication inhibition and host defence, alongside the downregulation of CMTM2, indicating alterations in immune-related functions. Similarly, in severe infection, upregulated genes like IGHV1-69 are linked to illness severity, while downregulated IL-13RA1 signifies disruptions in cytokine signaling. Overlapping DEGs between infection groups unveil shared biological processes, further elucidated through functional enrichment analysis, showcasing coordinated regulation of cellular processes and pathways. Integration of Dengue virus and human interaction network analysis reveals crucial insights into the mechanisms by which the virus mediates the disease progression and offers potential therapeutic opportunities for disease management.

Identification of biological significance of different stages of varicose vein development based on mRNA sequencing.

Normal veins could develop to varicose vein (VV) by some risk factors, and might further progress to shallow vein thrombosis (SVT). However, the molecular mechanism of key genes associated with the progression and regression of VV are still not thorough enough. In this study, the healthy control (HC), VV, and SVT vascular samples were collected for transcriptome sequencing. The differentially expressed genes (DEGs) were screened by "DESeq2", including DEGs1 (HC vs. VV), DEGs2 (HC vs. SVT) and DEGs3 (VV vs. SVT). And their functional enrichment analyses were conducted by "ClusterProfiler". The receiver operating characteristic (ROC) curve was used to obtain the key genes (KGs) of the pathogenesis of VV and SVT. The qRT-PCR assay was performed to validate the expressions of KGs. Immune cell infiltration analyses were conducted based on ssGSEA method. The competitive endogenous RNAs (ceRNAs) regulatory network was constructed. The target drugs of KGs were predicted using DrugBank database. The biofunctions of DACT3 were further investigated through a series of experiments in vitro. All of these DEGs were associated with inflammation and immunity related functions. Immune cell infiltration was significantly different between VV and SVT. Six key genes including PLP2, DACT3, LRRC25, PILRA, MSX1 and APOD that were associated with the progression and regression of VV were screened. The expression of LRRC25 and PILRA was significantly negatively associated with central memory T cell, and significantly positively associated with B cell. Besides, XIST was the critical regulator of multiple KGs. Cimetidine was potential drug for VV and SVT therapy. Overexpression of DACT3 significantly inhibited the proliferation and migration of vascular smooth muscle cells (VSMCs), and affected their cell cycle and phenotypic transition. This study identified six key genes associated with the progression and regression of VV. Among them, DACT3 was proved to hinder VV progression. These findings may help to deepen understanding its underlying mechanisms.

Identification of potential new T cell activation molecules: a Bioinformatic Approach.

T-cell activation is central for the initiation of T cell mediated adaptive immune response and is the result of the close communication between the Antigen Presenting Cell (APC) and the T lymphocyte. Although T-cell activation is currently well understood, and many intracellular pathways are well characterized, nevertheless new players are constantly identified, and this complements the known protein interactome. In this work we aimed to identify new proteins involved in T cell activation. We reviewed and analyzed results of microarray gene expression datasets reported in the public database GEO-NCBI. Using data from GSE136625, GSE50971, GSE13887, GSE11989 and GSE902 we performed different comparisons using R and other bioinformatic tools including GEO2R and we report here upregulated genes that have no previous reports in immune related functions and with potential participation upon T-cell activation. Our results indicate that RND3, SYT10, IgSF6 and PIN1 are potential new T-cell activation molecules.

Time series analysis combined with transcriptome sequencing to explore characteristic genes and potential molecular mechanisms associated with ultrasound-guided microwave ablation of glioma

Objective This study aimed to explore marker genes and their potential molecular mechanisms involved in US-guided MWA for glioma in mice. Method The differentially expressed genes (DEGs1 and DEGs2) and lncRNAs (DELs1 and DELs2) were obtained between Non (glioma tissues without MWA) and T0 groups (0h after MWA), as well as between Non and T24 groups (24h after MWA). The down-regulation cluster genes (CONDOWNDEGs) and upregulation cluster genes (CONUPDEGs) were identified by time series analysis. Candidate genes were obtained by overlapping CONDOWNDEGs with downregulation DEGs (DOWNDEGs)1 and DOWNDEGs2, as well as CONUPDEGs with up-regulation DEGs (UPDEGs)1 and UPDEGs2. The expressions of immune checkpoints and inflammatory factors, gene set enrichment analysis (GSEA), and protein subcellular localization were performed. The eXpression2Kinases (X2K), GeneMANIA, transcription factor (TF), and competing endogenous (ce) RNA regulatory networks were conducted. The expression of marker genes was validated by quantitative real-time polymerase chain reaction (qRT-PCR). Results Five marker genes (IL32, VCAM1, IL34, NFKB1 and CXCL13) were identified, which were connected with immune-related functions. Two immune checkpoints (CD96 and TIGIT) and six inflammatory factors played key roles in US-guided MWA for glioma. ceRNA regulatory networks revealed that miR-625-5p, miR-625-3p, miR-31-5p and miR-671-5p were associated with target genes. qRT-PCR indicated both IL32, VCAM1, and NFKB1 were potential markers under US-guided MWA-related time series analysis. Conclusion The use of US-guided MWA might be a practical method for influencing the function of target genes, regulating time frames to decrease inflammation, and stimulating immune responses in glioma therapy.

Unraveling the regulatory cell death pathways in gastric cancer: a multi-omics study.

Gastric cancer (GC) is a prevalent form of cancer worldwide and has a high death rate, with less than 40% of patients surviving for 5years. GC demonstrates a vital characteristic of evading regulatory cell death (RCD). However, the extent to which RCD patterns are clinically significant in GC has not been well investigated. The study created a regulatory cell death index (RCDI) signature by employing 101 machine-learning algorithms. These algorithms were based on the expression files of 1292GC patients from 6 multicenter cohorts. RCDI is a reliable and robust determinant of the likelihood of surviving in general. Furthermore, the precision of RCDI surpasses that of the 20 signatures that have been previously disclosed. The presence of RCDI signature is closely linked to immunological characteristics, such as the infiltration of immune cells, the presence of immunotherapy markers, and the activation of immune-related functions. This suggests that there is a higher level of immune activity in cases with RCDI signature. Collectively, the use of RCDI has the potential to be a strong and encouraging method for enhancing the clinical results of individual individuals with GC.

Medicago truncatula SOBIR1 controls pathogen immunity and specificity in the Rhizobium-legume symbiosis.

Medicago truncatula Nod Factor Perception (MtNFP)plays a role in both the Rhizobium-Legume (RL)symbiosis and plant immunity, and evidence suggests that the immune-related function of MtNFP is relevant for symbiosis. To better understand these roles of MtNFP, we sought to identify new interacting partners. We screened a yeast-2-hybrid cDNA library from Aphanomyces euteiches infected and noninfected M. truncatula roots. The M. truncatula leucine-rich repeat (LRR)receptor-like kinase SUPPRESSOR OF BIR1 (MtSOBIR1)was identified as an interactor of MtNFP and was characterised for kinase activity, and potential roles in symbiosis and plant immunity. We showed that the kinase domain of MtSOBIR1 is active and can transphosphorylate the pseudo-kinase domain of MtNFP. MtSOBIR1 could functionally complement Atsobir1 and Nbsobir1/sobir1-like mutants for defence activation, and Mtsobir1 mutants were defective in immune responses to A. euteiches. For symbiosis, we showed that Mtsobir1 mutant plants had both a strong, early infection defect and defects in the defence suppression in nodules, and both effects were plant genotype- and rhizobial strain-specific. This work highlights a conserved function for MtSOBIR1 in activating defence responses to pathogen attack, and potentially novel symbiotic functions of downregulating defence in association with the control of symbiotic specificity.

Decoding functional impact of epigenetic regulator mutations on ligand-receptor interaction perturbations for evaluation of cancer immunotherapy.

Cellular crosstalk mediated by ligand-receptor interactions largely complicates the tumour ecosystem, resulting in heterogeneous tumour microenvironments that affect immune response and clinical benefits from immunotherapy. Epigenetic mechanisms are pivotal to expression changes of immune-related genes and can modulate the anti-tumour immune response. However, the functional consequences of disrupted epigenetic regulators (ERs) on ligand-receptor interactions in the tumour microenvironment remain largely unexplored. Here, we proposed mutations of ERs in perturbed interactions (MERIN), a molecular network-based approach that incorporates multi-omics data, to infer the potential consequences of ER mutations on ligand-receptor interaction perturbations. Leveraging cancer genomic profiles and molecular interaction data, we comprehensively decoded the functional consequences of ER mutations on dysregulated ligand-receptor interactions across 33 cancers. The dysregulated ligand-receptor genes were indeed enriched in cancer and immune-related function. We demonstrated the potential significance of PD1-PDL1 interaction-related ER mutations in stratifying cancer patients from multiple independent data cohorts. The ER mutation group showed distinct immunological characterizations and prognoses. Furthermore, we highlighted that the ER mutations could potentially predict clinical outcomes of immunotherapy. Our computational and clinical assessment underscore the utility of MERIN for elucidating the functional relevance of ER mutations in cancer immune response, potentially aiding patients' stratification for immunotherapy.

Identification of Pyroptosis-Related Molecular Subtypes and Diagnostic Model development in Major Depressive Disorder.

Major depressive disorder (MDD) is a prevalent psychological disorder associated with inflammation, with complex pathological mechanisms. Pyroptosis has been suggested to contribute to inflammation in central nervous system diseases. Little research, however, has examined what role pyroptosis played in MDD. In the present study, the differential expression pyroptosis-related genes (DE-PRGs) in MDD were identified from the GEO database (GSE98793 and GSE19738). Then, consensus clustering analysis was used to evaluate differences in MDD molecular subtypes characteristics based on PRGs. The characteristic diagnostic biomarkers for MDD were identified by Weighted Correlation Network Analysis (WGCNA) and multiple machine learning algorithms. Three intersection genes (GZMA, AKR1C3, and CD52) were obtained, which are expected to become potential biomarkers for MDD with excellent reliability and accuracy. Subsequently, the immune infiltration characteristics result indicated that the development of MDD is mediated by immune-related function, where three DE-PRGs were strongly related to the immune infiltration landscape of MDD. The biological experiments in vitro further proved that three unique PRGs are emerging as important players in MDD diagnosis. Our research aimed to provide novel ideas and biomarkers targeting MDD.

Diagnostic value of the Sirtuins family in acute rejection of kidney transplantation assessed on the basis of transcriptomics and animal experiments

BackgroundThe Sirtuins (SIRT) family plays a key role in the diagnosis and treatment of many renal diseases, but no studies have been reported in acute rejection of kidney transplantation. The aim of this study was to explore the diagnostic value of SIRT family change characteristics in acute rejection of kidney transplantation. MethodsWe first explored the SIRT family expression profile in renal tissues using the HPA database; subsequently, we explored the potential biological functions and mechanistic changes during acute rejection of kidney transplantation by GSEA enrichment analysis. The Cibersort algorithm specifies the level of immune cell infiltration and explores the correlation between the SIRT family and immune cells using correlation analysis; Next, we constructed a diagnostic model using “Logistic regression analysis” and “Nomogram model”, and evaluated the diagnostic model using calibration curves and ROC curves, and the decision curve (DCA) was used to evaluate the clinical diagnostic value of SIRT family changes; Finally, we constructed a model of acute rejection of rat kidney transplantation, and assessed rat kidney function by detecting the levels of urea nitrogen and creatinine in serum. Meanwhile, the expression level of SIRT family in kidney tissues was initially verified by transcriptome sequencing and RT-PCR. ResultsWe found that all seven SIRT family members were located and expressed in renal tissues. The results of enrichment analysis revealed that a large number of immune-related biological functions and pathways are activated during acute rejection of kidney transplantation, the difference was statistically significant (p < 0.05). The Cibersort algorithm revealed significant changes in the level of infiltration of 10 immune cells (p < 0.05), while correlation analysis revealed a strong link between the SIRT family and immune cells (p < 0.05). We constructed a diagnostic model for acute rejection using seven SIRT families, and the ROC curves(AUC = 0.71)and calibration curves proved their good diagnostic value, and the DCA curves also proved the role of SIRT families in clinical decision-making. Next, we again demonstrated the good diagnostic performance of the SIRT family in ABMR and TCMR, respectively(ROC curves:AUC = 0.64，AUC = 0.81). Finally, in a rat model of acute rejection of kidney transplantation, we found that renal function (BUN and creatinine) was significantly impaired in rats in the Allo group compared to rats in the Syn group (P < 0.05). Meanwhile, by transcriptome analysis and RT-PCR assay, we found that, except for SIRT1, the remaining SIRT family members were significantly changed in kidney tissues (P < 0.05). ConclusionThe SIRT family has significant changes during acute rejection in kidney transplantation, and the SIRT family may be able to serve as a potential therapeutic target for alleviating acute rejection in kidney transplantation.

WD repeat domain 43 as a new predictive indicator and its connection with tumor immune cell infiltration in pan-cancer.

WD repeat domain 43 (WDR43) is a protein component that encodes WD-repeats and is involved in ribosome biogenesis. However, little is known about the role of WDR43 in cancer prognosis and immune modulation. In this study, we analyzed the expression and prognostic significance of WDR43 in pan-cancer using the Cancer Genome Atlas, the Genotype-Tissue Expression, and the Human Protein Atlas. We also examined the differential expression of WDR43 in liver hepatocellular carcinoma (LIHC) and adjacent tissues of 48 patients using immunohistochemistry. Additionally, we investigated the correlation between WDR43 and clinical characteristics, gene alterations, tumor mutation burden, microsatellite instability, mismatch repair, tumor microenvironment, immune infiltrating cells, and immune-related genes using bioinformatics methods. Gene set enrichment analysis was conducted, and potential biological mechanisms were identified. Immunohistochemistry staining showed that WDR43 was overexpressed in LIHC among 48 patients. Upregulation of WDR43 was associated with unfavorable prognosis, including overall survival in various types of cancer such as LIHC, uterine corpus endometrial cancer, head and neck squamous cell carcinoma, and pancreatic adenocarcinoma. Differential expression of WDR43 was significantly correlated with microsatellite instability, mismatch repair, and immune cell infiltration. Gene ontology annotation analysis revealed that these genes were significantly enriched in immune-related functions, including immune response, immune regulation, and signaling pathways. We conducted a thorough investigation of the clinical features, phases of tumor development, immune infiltration, gene mutation, and functional enrichment analysis of WDR43 in various types of cancer. This research offers valuable insight into the significance and function of WDR43 in clinical therapy.

DArTseq-Based, High-Throughput Identification of Novel Molecular Markers for the Detection of Blackleg (Leptosphaeria Spp.) Resistance in Rapeseed.

Blackleg disease, caused by Leptosphaeria spp. fungi, is one of the most important diseases of Brassica napus, responsible for severe yield losses worldwide. Blackleg resistance is controlled by major R genes and minor quantitative trait loci (QTL). Due to the high adaptation ability of the pathogen, R-mediated resistance can be easily broken, while the resistance mediated via QTL is believed to be more durable. Thus, the identification of novel molecular markers linked to blackleg resistance for B. napus breeding programs is essential. In this study, 183 doubled haploid (DH) rapeseed lines were assessed in field conditions for resistance to Leptosphaeria spp. Subsequently, DArTseq-based Genome-Wide Association Study (GWAS) was performed to identify molecular markers linked to blackleg resistance. A total of 133,764 markers (96,121 SilicoDArT and 37,643 SNP) were obtained. Finally, nine SilicoDArT and six SNP molecular markers were associated with plant resistance to Leptosphaeria spp. at the highest significance level, p < 0.001. Importantly, eleven of these fifteen markers were found within ten genes located on chromosomes A06, A07, A08, C02, C03, C06 and C08. Given the immune-related functions of the orthologues of these genes in Arabidopsis thaliana, the identified markers hold great promise for application in rapeseed breeding programs.

Genome−wide association analysis to search for new loci associated with stroke risk in Northwestern Chinese population

Background and PurposeGenetic factors play an important role in the pathogenesis of stroke(S). This study aimed to screen the loci associated with S risk in northwestern Chinese population by genome-wide association analysis (GWAS). MethodsA total of 1394 subjects, including 682 S patients and 692 controls, were enrolled in this study. SPSS 25.0 software was used for statistical analysis, and the independent sample t-test as well as Chi-square test were used to analyze the differences in age and gender between the case and control groups. The Precision Medicine Diversity Array (PMDA) genotyping chip was used in this study. The genotyping platform was the Gene Titan multi-channel instrument, and the Axiom Analysis Suite 6.0 software was used for the data analyzing. Besides, the LASSO analysis, SNP-SNP and GO/KEGG analysis were conducted to analyze the association between significant loci and S risk. ResultsA total of 30 SNPs were found to be associated with the S risk based on additive model (p < 5 × 10-8). After the LASSO screening, 22 SNPs showed the diagnostic value in S. The SNPs interaction analysis further screened the SNP-SNP interaction groups associated with the S risk(p < 0.05). Finally, the GO/KEGG analysis discovered the suggestive significance loci could be involved in the S development mainly by immune-related functions and pathways. ConclusionThis study discovered 30 S related SNPs and analyzed the potential pathways associated with genes located on the 30 SNPs, which were beneficial for enriching the genetic mechanism analysis of S in northwestern Chinese population.

Analysis of sex-biased gene expression in a Eurasian admixed population.

Sex-biased gene expression differs across human populations; however, the underlying genetic basis and molecular mechanisms remain largely unknown. Here, we explore the influence of ancestry on sex differences in the human transcriptome and its genetic effects on a Eurasian admixed population: Uyghurs living in Xinjiang (XJU), by analyzing whole-genome sequencing data and transcriptome data of 90 XJU and 40 unrelated Han Chinese individuals. We identified 302 sex-biased expressed genes and 174 sex-biased cis-expression quantitative loci (sb-cis-eQTLs) in XJU, which were enriched in innate immune-related functions, indicating sex differences in immunity. Notably, approximately one-quarter of the sb-cis-eQTLs showed a strong correlation with ancestry composition; i.e. populations of similar ancestry tended to show similar patterns of sex-biased gene expression. Our analysis further suggested that genetic admixture induced a moderate degree of sex-biased gene expression. Interestingly, analysis of chromosome interactions revealed that the X chromosome acted on autosomal immunity-associated genes, partially explaining the sex-biased phenotypic differences. Our work extends the knowledge of sex-biased gene expression from the perspective of genetic admixture and bridges the gap in the exploration of sex-biased phenotypes shaped by autosome and X-chromosome interactions. Notably, we demonstrated that sex chromosomes cannot fully explain sex differentiation in immune-related phenotypes.

An integrated pan-cancer assessment of prognosis, immune infiltration, and immunotherapy response for B7 family using multi-omics data

AimsB7 molecules (B7s) are crucial synergistic signals for effective immune surveillance against tumor cells. While previous studies have explored the association between the B7 family and cancer, most have been limited to specific genes or cancer subtypes. Main methodsOur study utilized multi-omics data to investigate potential correlations between B7s expression (B7s exp.) and prognosis, clinicopathological features, somatic mutations (SMs), copy number variations (CNVs), immune characteristics, tumor microenvironment (TME), microsatellite instability, tumor mutation burden, immune checkpoint gene (ICG), and drug responsiveness in TCGA tumors. Furthermore, the connection between B7s exp. and immunotherapy (IT) performance assessed in various validated datasets. Following this, immune infiltration analysis (IIA) was conducted based on B7s exp., CNVs, or SMs in bladder cancer (BLCA), complemented by real-time PCR (RT-PCR) and protein confirmation of B7-H3. Key findingsAcross most cancer types, B7s exp. was related to prognosis, clinicopathological characteristics, mutations, CNVs, ICG, TMB, TME. The examination of sensitivity to anticancer drugs unveiled correlations between B7 molecules and different drug sensitivities. Specific B7s exp. patterns were linked to the clinical effectiveness of IT. Using GSEA, several enriched immune-related functions and pathways were identified. Particularly in BLCA, IIA revealed significant connections between B7 CNVs, mutation status, and various immune cell infiltrates. RT-PCR confirmed elevated B7-H3 gene levels in BLCA tumor tissues. SignificanceThis study confirmed the significance of B7s exp. and genomic changes in predicting outcomes and treatment across different cancer types. Moreover, they indicate a critical function of B7s in BLCA and their potential as IT biomarkers.

Systematic pan-cancer analysis insights into ICAM1 as an immunological and prognostic biomarker.

Intercellular adhesion molecule 1 (ICAM1) is a cell surface adhesion glycoprotein in the immunoglobulin supergene family. It is associated with several epithelial tumorigenesis processes, as well as with inflammation. However, the function of ICAM1 in the prognosis of tumor immunity is still unclear. This study aimed to examine the immune function of ICAM1 in 33 tumor types and to investigate the prognostic value of tumors. Using datasets from the Cancer Genome Atlas (TCGA), Genotype Tissue Expression (GTEx), Cancer Cell Lines Encyclopedia (CCLE), Human Protein Atlas (HPA), and cBioPortal, we investigated the role of ICAM1 in tumors. We explored the potential correlation between ICAM1 expression and tumor prognosis, gene mutations, microsatellite instability, and tumor immune cell levels in various cancers. We observed that ICAM1 is highly expressed in multiple malignant tumors. Furthermore, ICAM1 is negatively or positively associated with different malignant tumor prognoses. The expression levels of ICAM1 were correlated with the tumor mutation burden (TMB) in 11 tumors and with MSI in eight tumors. ICAM1 is a gene associated with immune infiltrating cells, such as M1 macrophages and CD8+ T cells in gastric and colon cancer. Meanwhile, the expression of ICAM1 is associated with several immune-related functions and immune-regulation-related signaling pathways, such as the chemokine signaling pathway. Our study shows that ICAM1 can be used as a prognostic biomarker in many cancer types because of its function in tumorigenesis and malignant tumor immunity.

Integrating Chinese medicine into mainstream cancer therapies: a promising future.

Malignant tumors are complex systemic chronic diseases and one of the major causes of human mortality. Targeted therapy, chemotherapy, immunotherapy, and radiotherapy are examples of mainstream allopathic medicine treatments that effective for intermediate and advanced malignant tumors. The ongoing use of conventional allopathic medicine has resulted in adverse responses and drug resistance, which have hampered its efficacy. As an important component of complementary and alternative medicine, Chinese medicine has been found to have antitumor effects and has played an important role in enhancing the therapeutic sensitivity of mainstream allopathic medicine, reducing the incidence of adverse events and improving immune-related functions. The combined application of adjuvant Chinese medicine and mainstream allopathic medicine has begun to gain acceptance and is gradually used in the field of antitumor therapy. Traditional natural medicines and their active ingredients, as well as Chinese patent medicines, have been proven to have excellent therapeutic efficacy and good safety in the treatment of various malignant tumors. This paper focuses on the mechanism of action and research progress of combining the above drugs with mainstream allopathic medicine to increase therapeutic sensitivity, alleviate drug resistance, reduce adverse reactions, and improve the body's immune function. To encourage the clinical development and use of Chinese herb adjuvant therapy as well as to provide ideas and information for creating safer and more effective anticancer medication combinations, the significant functions of Chinese herb therapies as adjuvant therapies for cancer treatment are described in detail.

Analysis of lncRNA-miRNA-mRNA interactions identified a novel biomarker LINC00657 to improve prognosis prediction of papillary thyroid carcinoma

BackgroundPapillary thyroid cancer (PTC) is the most common type of thyroid cancer. Identification of novel biomarkers can potentially help explore the underlying molecular mechanisms of PTC. Long non-coding RNAs (lncRNAs) are involved in cancer development. However, understanding the role of lncRNA in PTC remains challenging. MethodsBased on the competitive endogenous RNA (ceRNA) theory, we constructed a comprehensive PTC-related lncRNA-miRNA-mRNA network using data from The Cancer Genome Atlas. To evaluate the prognostic power, we performed survival analysis for patients with PTC with low and high lncRNA expression levels, and examined the relationship between lncRNA and immune-related functions. ResultsWe identified a hub node, long intergenic non-coding RNA, LINC00657, as a novel prognostic biomarker in PTC. LINC00657 was differentially expressed between tumor and adjacent normal samples. Low LINC00657 expression levels was significantly associated with better survival outcome. Our functional analyses showed that LINC00657 was related with infiltration of CD8+ T cell and macrophage; immune check point molecules; and immune metagenes such as IgG, LCK, MHC_I/II and etc. These results suggest that LINC00657 is an immune-related biomarker with potential clinical applicability. Additionally, cancer-related signaling pathway and high frequency of gene BRAF mutation were found in PTC samples with high LINC00657 expression level, which were consistent with previous findings. ConclusionLINC00657 is an immune-related biomarker that can potentially improve prognosis prediction in PTC. Our study provided new treatment target of PTC in clinical practice and offered the novel insights in elucidating the functional role of lncRNAs.

Recovery of synaptic loss and depressive-like behavior induced by GATA1 through blocking of the neuroinflammatory response.

GATA1, a member of the GATA transcription factor family, is a critical factor in hematopoietic system development. In a previous study, we demonstrated the increased expression of GATA1 in the dorsolateral prefrontal cortex (dlPFC) of patients suffering from depression and described its role as a transcriptional repressor of synapse-related genes. In this study, we investigated how GATA1 globally altered gene expression using multi-omics approaches. Through the combined analyses of ChIPseq, mRNAseq, and small RNAseq, we profiled genes that are potentially affected by GATA1 in cultured cortical neurons, and Gene Ontology (GO) analysis revealed that GATA1 might be associated with immune-related functions. We hypothesized that GATA1 induces immune activation, which has detrimental effects including synapse loss and depressive-like behavior. To test this hypothesis, we first performed a microglial morphometric analysis of a brain having overexpression of GATA1 because microglia are the resident immune cells of the central nervous system. Fractal analysis showed that the ramification and process length of microglia decreased in brains having GATA1 overexpression compared to the control, suggesting that GATA1 overexpression increases the activation of microglia. Through flow cytometry and immunohistochemical analysis, we found that activated microglia showed pro-inflammatory phenotypes characterized by the expression of CD86 and CD68. Finally, we demonstrated that the effects of GATA1 overexpression including synapse loss and depressive-like behavior could be blocked by inhibiting microglial activation using minocycline. These results will elucidate the regulatory mechanisms of GATA1 that affect pathophysiological conditions such as depression and provide a potential target for the treatment of depression.

Construction of an immune-related gene prognostic model with experimental validation and analysis of immune cell infiltration in lung adenocarcinoma.

There is a correlation between tumors and immunity with the degree of immune cell infiltration in tumors being closely related to tumor growth and progression. Therefore, the present study identified immune-related prognostic genes and evaluated the immune infiltration level in lung adenocarcinoma (LUAD). This study performed Kyoto Encyclopedia of Genes and Genomes, Gene Ontology, and Gene Set Enrichment Analysis (GSEA) enrichment analyses on differential immune-associated genes. A risk model was created and validated using six immune-related prognostic genes. Reverse transcription-quantitative PCR was used to assess the prognostic gene expression in non-small cell lung cancer cells. Immune cell infiltration in LUAD was analyzed using the CIBERSORT method. Single sample GSEA was used to compare Tumor Immune Dysfunction and Exclusion (TIDE) scores between high and low-risk groups and to assess the activation of thirteen immune-related pathways. Multifactor Cox proportional hazards model analysis identified six prognostic risk genes (S100A16, FURIN, FGF2, LGR4, TNFRSF11A and VIPR1) to construct a risk model. The survival and receiver operating characteristic curves indicated that patients with higher risk scores had lower overall survival rates. The expression levels of prognostic genes S100A16, FURIN, LGR4, TNFRSF11A and VIPR1 were significantly increased in LUAD. B cells naive, plasma cells, T cells CD4 memory activated, T cells follicular helper, T cells regulatory, NK cells activated, macrophages M1, macrophages M2, and Dendritic cells resting cells showed elevated expression in LUAD. The prognostic genes were differentially associated with individual immune cells. Immune-related function scores, such as those for antigen presenting cell (APC) co-stimulation, APC co-inhibition, check-point, Cytolytic-activity, chemokine receptor, parainflammation, major histocompatibility complex-class-I, type-I-IFN-reponse and T-cell-co-inhibition, were higher in the high-risk group compared with the low-risk group. Furthermore, the TIDE score of the high-risk group was significantly lower than the low-risk group. This immune-related gene prognostic model has the potential to predict the prognosis of LUAD patients, supporting the development of a personalized clinical diagnosis and treatment plan.