Pathological image profiling identifies onco-microbial, tumor immune microenvironment, and prognostic subtypes of colorectal cancer.

Histology slide, tissue microbes, and the host gene expression can be independent prognostic factors of colorectal cancer (CRC), but the underlying associations and biological significance of these multimodal omics remain unknown. Here, we comprehensively profiled the matched pathological images, intratumoral microbes, and host gene expression characteristics in 527 patients with CRC. By clustering these patients based on histology slide features, we classified the patients into two histology slide subtypes (HSS). Onco-microbial community and tumor immune microenvironment (TIME) were also significantly different between the two subtypes (HSS1 and HSS2) of patients. Furthermore, variation in intratumoral microbes-host interaction was associated with the prognostic heterogeneity between HSS1 and HSS2. This study proposes a new CRC classification based on pathological image features and elucidates the process by which tumor microbes-host interactions are reflected in pathological images through the TIME.

Co-expression of IL-21-Enhanced NKG2D CAR-NK cell therapy for lung cancer.

BACKGROUND: Adoptive cell therapy has achieved great success in treating hematological malignancies. However, the production of chimeric antigen receptor T (CAR-T) cell therapy still faces various difficulties. Natural killer (NK)-92 is a continuously expandable cell line and provides a promising alternative for patient's own immune cells. METHODS: We established CAR-NK cells by co-expressing natural killer group 2 member D (NKG2D) and IL-21, and evaluated the efficacy of NKG2D-IL-21 CAR-NK cells in treating lung cancer in vitro and in vivo. RESULTS: Our data suggested that the expression of IL-21 effectively increased the cytotoxicity of NKG2D CAR-NK cells against lung cancer cells in a dose-dependent manner and suppressed tumor growth in vitro and in vivo. In addition, the proliferation of NKG2D-IL-21 CAR-NK cells were enhanced while the apoptosis and exhaustion of these cells were suppressed. Mechanistically, IL-21-mediated NKG2D CAR-NK cells function by activating AKT signaling pathway. CONCLUSION: Our findings provide a novel option for treating lung cancer using NKG2D-IL-21 CAR-NK cell therapy.

Pan-cancer analyses reveal the stratification of patient prognosis by viral composition in tumor tissues.

The associations between cancer and bacteria/fungi have been extensively studied, but the implications of cancer-associated viruses have not been thoroughly examined. In this study, we comprehensively characterized the cancer virome of tissue samples across 31 cancer types, as well as blood samples from 23 cancer types. Our findings demonstrated the presence of viral DNA at low abundances in both tissue and blood across major human cancers, with significant differences in viral community composition observed among various cancer types. Furthermore, Cox regression analyses conducted on four cancers, including Head and Neck squamous cell carcinoma (HNSC), Kidney renal clear cell carcinoma (KIRC), Stomach adenocarcinoma (STAD), and Uterine Corpus Endometrial Carcinoma (UCEC), revealed strong correlation between viral composition/abundance in tissues and patient survival. Additionally, we identified virus-associated prognostic signatures (VAPS) for these four cancers, and discerned differences in the interplay between VAPS and dominant bacteria in tissues among patients with varying survival risks. Notably, clinically relevant analyses revealed prognostic capacities of the VAPS in these four cancers. Taken together, our study provides novel insights into the role of viruses in tissue in the prognosis of multiple cancers and offers guidance on the use of tissue viruses to stratify prognosis for patients with cancer.

[Effect of Flax lignans on apoptosis of growth plate chondrocytes in rats].

OBJECTIVE: To compare the effects of different concentrations of linolenin on inhibiting apoptosis of chondrocytes in the growth plate, and to screen the optimal concentration of linolenin, so as to provide theoretical support for delaying epiphyseal closure and promoting long bone growth in rats. METHODS: Two 4-week-old male SD rats (SPF grade) with a body mass of 80 g were selected. The growth plate cartilage of rat tibia and femur was dissected and isolated in vitro to obtain growth plate chondrocytes for culture. The chondrocytes were observed and identified by inverted phase contrast microscope and typeⅡ collagen immunofluorescence test, and then 20 ng/ml IL-1ß was used to induce apoptosis of growth plate chondrocytes as model group, and added with 1, 10, 20, 40 µM linolenin as the experimental group, and 5 µM letrozole as the positive control group. The cells were cultured for 24 and 48 hours respectively. The drug promoted cell proliferation was observed by MTT method, and the drug inhibited cell apoptosis was detected by flow cytometry. RESULTS: Contents 1, 10, 20, 40 µM could promote cell proliferation in varying degrees, and the principle was that the drug inhibits IL-1ß induced chondrocyte apoptosis in the growth plate, and the optimal concentration of drugs to inhibit apoptosis was 20 µM. CONCLUSION: The appropriate concentration of linseed lignans can significantly inhibit the apoptosis of chondrocytes in the growth plate of rats, and the optimal drug concentration is 20 µM. It provides possibility for delayed bone closure and longer growth time to promote bone growth during development.

Brahma-related gene 1 induces apoptosis in a p53-dependent manner in human rheumatoid fibroblast-like synoviocyte MH7A.

Blocked apoptosis and aggressive inflammatory responses occur in fibroblast-like synoviocyte (FLS) of rheumatoid arthritis (RA) patients. Although Brahma-related gene 1 (BRG1) is considered as a tumor suppressor, few research covers its role in RA. This study aims to reveal effects and potential mechanisms of BRG1 in human FLS cell line MH7A.BRG1 expression in MH7A cells was altered by transfection of overexpression vectors or short hairpin RNAs (shRNAs). Cell viability and apoptosis were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry after transfection. Factors involved in inflammation and apoptosis were quantified by qPCR and Western blot. The interaction between BRG1 and p53 was assessed by immunoprecipitation (IP).Results showed that BRG1 overexpression significantly suppressed MH7A cell viability and induced apoptosis (P < 0.01), and its knockdown had opposite effects. BRG1 reduced mRNA levels of matrix metallopeptidase 3, TIMP metallopeptidase inhibitor 2, cyclooxygenase 2, and interleukin 6, implying its suppressive effects on inflammation. BRG1 interacted with and promoted p53 (P < 0.05). B-cell chronic lymphocytic leukemia/lymphoma 2 was suppressed (P < 0.05), while cytochrome c, caspase 3 (CASP3) and CASP9 were activated (P < 0.01) by BRG1. However, the regulation on these factors was abrogated by p53 knockdown (P < 0.01).These findings suggest that BRG1 may induce apoptosis and suppress inflammation in MH7A cells. Potential functional mechanisms involve the regulation of apoptotic factors by BRG1, which may depend on the recruitment and promotion of p53. This study provides the essential proof for applying BRG1 to the molecular therapy of RA.