Search

Background: Cancer stem cells (CSCs) are regarded as the root of tumor progression, thus representing an anti-cancer therapy through targeting this cell sub-population. Methods: Non-small cell lung cancer (NSCLC) CSCs were enriched by non-adherent spheroid formation analysis. Lentivirus infection was used to stably change gene expression. Cell cycle, EdU incorporation, cell apoptosis, cell viability, ALDH1 activity, spheroid formation and in vivo tumor initiation assays were performed to detect the effects of Cryptotanshinone (CT), a traditional Chinese herb medicine, on the stemness of NSCLC cells. RNA-sequencing combined qRT-PCR and western blot analysis were constructed to explore the underlying mechanism contributing to CT-mediated effects. Results: CT could attenuate the stemness of NSCLC CSCs, as evident by the reduced spheroid formation ability, stemness marker expression and ALDH1 activity. Additionally, CT provoked NSCLC CSCs entry into the cell cycle. RNA-sequencing analysis showed that Hippo signaling pathway was highly enriched in NSCLC CSCs with CT treatment. Further experiments disclosed that CT decreased TAZ (a regulatory master of Hippo pathway) expression via promoting its nuclear-cytoplasm translocation in NSCLC CSCs. Also, overexpression of TAZ partially saved the attenuation of CT on the stemness of NSCLC CSCs. Notably, CT enhanced the sensitivity of tyrosine kinase inhibitor (TKI) and chemotherapy in NSCLC CSCs. Conclusions: This work reveals that CT attenuates NSCLC CSC stemness, implying the possibility of CT as an adjuvant therapy for NSCLC. [ABSTRACT FROM AUTHOR]

Objective: To identify primary Sjögren’s syndrome (pSS) patients with arthralgia at risk for osteoarthritis (OA) or arthritis. Methods: This study included 368 pSS patients admitted to a mono-centric from March 2010 to December 2020. Patients were divided into groups according to whether complicated with OA or arthritis. Data were analyzed to determine the differences in demographical characteristics, symptoms, and laboratory examination. Results: The involvement of the OA joints was predominately knee and spine sites (including cervical and lumbar spine degeneration). When diagnosing arthritis, it was mainly peripheral symmetric polyarthritis, the most affected sites were the interphalangeal and metacarpophalangeal joints. There were significant differences in age, disease duration, uric acid (UA), and total cholesterol (TC) between pSS-OA and pSS-nOA patients (P < 0.050). Logistic regression analysis showed that age (OR = 1.965; P = 0.009) and joint pain (OR = 3.382; P < 0.001) were dangerous factors associated with OA. Interestingly, although the level of UA, TC, and triglycerides (TG) was shown to be positive with OA, there was no statistical significance after the OR was computed in the four-cell table. In pSS-arthritis, EULAR Sjögren's syndrome disease activity index (ESSDAI) (P = 0.011), the frequency of joint pain (P < 0.001), and muscular involvement (P = 0.037) were higher than non-arthritis group. In pSS patients only presenting with joint pain, arthritis patients had higher ESSDAI and system involvements, but lower UA and TG levels compared with OA group (P < 0.050). Conclusion: In pSS patients with arthralgia, OA accounted for the majority. pSS patients with advanced age and more pronounced metabolic characteristics, such as elevated blood lipids and uric acid, was a key factor in groups at risk for OA. However, arthritis patients had higher rates of dry mouth and eye, higher disease activity, antibodies positive, and more organs damage. In the future, it may be necessary to be more cautious in the diagnosis of joint manifestations in pSS patients in order to make the appropriate treatments. [ABSTRACT FROM AUTHOR]

Background: An increasing number of clinical studies have begun to explore combination strategies with immune checkpoint inhibitors, aiming to present new opportunities for overcoming anti-PD-1 treatment resistance in gastric cancer. Unfortunately, the exploration of certain immune checkpoint inhibitor combination strategies has yielded suboptimal results. Therefore, it is necessary to comprehensively analyze the expression patterns of immune checkpoints and identify optimal combination regimens of anti-PD-1 inhibitors with other immune checkpoint inhibitors. Methods: Leveraging single-cell RNA sequencing (scRNA-seq) and multivariate linear regression interaction models, we dissected the immune checkpoint expression characteristics of CD8+ T cells in gastric cancer and the immune checkpoint expression pattern (ICEP) mediating anti-PD-1 treatment resistance. Furthermore, we employed transcription factor analysis and CellOracle to explore the transcriptional regulatory mechanisms governing CD8+ T cell differentiation fates. Finally, we utilized Nichenet and spatial transcriptomic analysis to investigate the spatial expression patterns of immune checkpoints. Results: Interaction analysis indicated that, among the known immune checkpoints, co-expression of NKG2A and PD-1 might exert a more profound inhibitory effect on the proliferative capacity of CD8+ T cells. The co-expression analysis revealed differential co-expression pattern of PD-1 and NKG2A, defined as ICEP1 (CD8+ T cells co-expressing PD-1, CTLA-4, TIGIT, LAG-3 or CD38) and ICEP2 (CD8+ T cells solely expressing NKG2A or co-expressing with other immune checkpoints), reflecting the co-occurrence pattern of PD-1 and the mutual exclusivity of NKG2A. Further, these two ICEP CD8+ T cell subsets represented distinct CD8+ T cell differentiation fates governed by MSC and RUNX3. Notably, ICEP2 CD8+ T cells were associated with anti-PD-1 therapy resistance in gastric cancer. This phenomenon may be attributed to the recruitment of LGMN+ macrophages mediated by the CXCL16-CXCR6 signaling pathway. Conclusion: This study unveiled two distinct ICEPs and the mutually exclusivity and co-occurrence characteristics of CD8+ T cells in gastric cancer. The ICEP2 CD8+ T cell subset, highly expressed in gastric cancer patients resistant to anti-PD-1 therapy, may be recruited by LGMN+ macrophages through CXCL16-CXCR6 axis. These findings provide evidence for NKG2A as a novel immunotherapeutic target in gastric cancer and offer new insights into combination strategies for immune checkpoint inhibitors in gastric cancer. [ABSTRACT FROM AUTHOR]

Background: The experimental materials were a 60-year-old tea tree (Camellia sinensis cv. Shu Cha Zao; SCZ) (the mother plant) and 1-year-old and 20-year-old plants of SCZ that originated as mother plant cuttings. The aim of this study was to use high-throughput sequencing to study the spatial and dynamic distribution of endophytic fungi in different leaf niches (upper leaves, middle leaves, lower leaves) and rhizosphere soil on tea plants of different ages in the same garden. Results: Ascomycota (83.77%), Basidiomycota (11.71%), and Zygomycota (3.45%) were the dominant fungal phyla in all samples. Cladosporium (12.73%), Zymoseptoria (9.18%), and Strelitziana (13.11%) were the dominant genera in the leaf. Alpha diversity analysis revealed that endophytic communities in leaves differed from those in rhizosphere soil and different leaf niches had similar fungal diversity. Shannon's indices and NMDS analysis indicated significant differences in fungal diversity and composition among the SCZ trees of different ages (p ≤ 0.01). The abundance of Cladosporium and Zymoseptoria decreased with increasing SCZ age, whereas the abundance of Strelitziana increased. Conclusions: The results illustrate variation in endophytic fungi among different niches on tea plants of different ages. The distribution of endophytic fungi in leaves of C. sinensis shows spatiotemporal variation. [ABSTRACT FROM AUTHOR]

Background: The epigenetic regulator additional sex combs-like 1 (ASXL1) is an adverse prognostic factor in acute myeloid leukemia (AML). However, the mutational spectrum and prognostic factors of ASXL1-mutated (ASXL1+) AML are largely unknown. We aim to evaluate the risk factors influencing the prognosis of ASXL1+ AML. Methods: We performed next-generation sequencing (NGS) in 1047 cases of de novo AML and discovered 91 ASXL1+ AML (8.7%). The Log-Rank test and Kaplan-Meier were used to evaluate survival rate, and the Cox regression model was used to analyze multivariate analysis. Results: In a total of 91 ASXL1+ AML, 86% had one or more co-mutations. The factors that had adverse impact on overall survival (OS) and event-free survival (EFS) are defined as high risk factors, including age ≥ 60 years, WBC count ≥ 50 × 109/L, FLT3-ITD mutations, RUNX1 mutations, and absence of AML1-ETO fusion gene. ASXL1 mutations without any risk factor were classified as single-hit ASXL1+ AML; ASXL1 mutations accompanied with one of the risk factors was referred to as double-hit ASXL1+ AML; ASXL1 mutations with two or more of the risk factors were designated as triple-hit ASXL1+ AML. The combination of these risk factors had a negative influence on the prognosis of ASXL1+ AML. The median OS was not attained in single-hit ASXL1+ AML, 29.53 months in double-hit ASXL1+ AML, and 6.67 months in triple-hit ASXL1+ AML (P = 0.003). The median EFS was not attained in single-hit ASXL1+ AML, 29.53 months in double-hit ASXL1+ AML, and 5.47 months in triple-hit ASXL1+ AML (P = 0.002). Allogenic hematopoietic stem cell transplantation (allo-HSCT) improved the prognosis of double/triple-hit ASXL1+ AML patients. Conclusions: Our study provided new insights into the mutational spectrum and prognostic factors of ASXL1+ AML patients. Our primary data suggest that the risk factors in ASXL1+ AML contribute to the poor outcome of these patients. The management of ASXL1+ AML patients should be based on the risk factors and allo-HSCT is highly recommended for consolidation. [ABSTRACT FROM AUTHOR]

Background: Tumor-derived exosomes (TEXs) are involved in tumor progression and the immune modulation process and mediate intercellular communication in the tumor microenvironment. Although exosomes are considered promising liquid biomarkers for disease diagnosis, it is difficult to discriminate TEXs and to develop TEX-based predictive biomarkers.Methods: In this study, the gene expression profiles and clinical information were collected from The Cancer Genome Atlas (TCGA) database, IMvigor210 cohorts, and six independent Gene Expression Omnibus datasets. A TEXs-associated signature named TEXscore was established to predict overall survival in multiple cancer types and in patients undergoing immune checkpoint blockade therapies.Results: Based on exosome-associated genes, we first constructed a tumor-derived exosome signature named TEXscore using a principal component analysis algorithm. In single-cell RNA-sequencing data analysis, ascending TEXscore was associated with disease progression and poor clinical outcomes. In the TCGA Pan-Cancer cohort, TEXscore was elevated in tumor samples rather than in normal tissues, thereby serving as a reliable biomarker to distinguish cancer from non-cancer sources. Moreover, high TEXscore was associated with shorter overall survival across 12 cancer types. TEXscore showed great potential in predicting immunotherapy response in melanoma, urothelial cancer, and renal cancer. The immunosuppressive microenvironment characterized by macrophages, cancer-associated fibroblasts, and myeloid-derived suppressor cells was associated with high TEXscore in the TCGA and immunotherapy cohorts. Besides, TEXscore-associated miRNAs and gene mutations were also identified. Further experimental research will facilitate the extending of TEXscore in tumor-associated exosomes.Conclusions: TEXscore capturing tumor-derived exosome features might be a robust biomarker for prognosis and treatment responses in independent cohorts. [ABSTRACT FROM AUTHOR]

Background: The genus Rhododendron L. has been widely cultivated for hundreds of years around the world. Members of this genus are known for great ornamental and medicinal value. Owing to advances in sequencing technology, genomes and transcriptomes of members of the Rhododendron genus have been sequenced and published by various laboratories. With increasing amounts of omics data available, a centralized platform is necessary for effective storage, analysis, and integration of these large-scale datasets to ensure consistency, independence, and maintainability. Results: Here, we report our development of the Rhododendron Plant Genome Database (RPGD; http://bioinfor.kib.ac.cn/RPGD/), which represents the first comprehensive database of Rhododendron genomics information. It includes large amounts of omics data, including genome sequence assemblies for R. delavayi, R. williamsianum, and R. simsii, gene expression profiles derived from public RNA-Seq data, functional annotations, gene families, transcription factor identification, gene homology, simple sequence repeats, and chloroplast genome. Additionally, many useful tools, including BLAST, JBrowse, Orthologous Groups, Genome Synteny Browser, Flanking Sequence Finder, Expression Heatmap, and Batch Download were integrated into the platform. Conclusions: RPGD is designed to be a comprehensive and helpful platform for all Rhododendron researchers. Believe that RPGD will be an indispensable hub for Rhododendron studies. [ABSTRACT FROM AUTHOR]