Phenomics (Cham, Switzerland)最新文献

Integrins mediate cell adhesion and transmit cellular chemical and mechanical signals bidirectionally. Abnormal activation of integrin signals drives tumor initiation, invasion, metastasis, and therapeutic resistance. Therefore, integrins are ideal tumor theranostic biomarkers. Among the 24 known human integrins, the integrin αvβ3 has been the most intensively studied in tumor theranostics in the past 20 years. Here, we focus on the laminin receptors integrin α6β1 and α6β4, which consist of the α6 integrin subunit and either the β1 or β4 integrin subunit, respectively. Both of these proteins are overexpressed in many cancers, and their expression has been linked to poor prognosis in some cancers. Over the last decade, we and our collaborators have developed several types of integrin α6-targeted probes, including single-photon emission computed tomography (SPECT), positron emission tomography (PET), magnetic resonance imaging (MRI) and near-infrared fluorescent imaging (NIRF) probes, for the molecular imaging of tumors. Among them, an integrin α6-targeted SPECT probe has been proven to be safe and efficient for detecting breast cancer in the first-in-human pilot study. Moreover, we have developed integrin α6-targeted therapeutic strategies for the treatment of tumors. In this review, we highlight the latest progress in integrin α6-targeted tumor theranostics.

Quantifying individual health status from increasingly accumulated omics data is essential for both early prevention and intervention of diseases, which attracts great attention from communities of biology and medicine. Most of the existing approaches mainly classify individuals into different catalogues or classes based on phenotypes and biomarkers. However, an individual's health status from a dynamical systems viewpoint can be viewed as a non-equilibrium steady state, which can generally be characterized by two key features, i.e. (1) homeostatic potential that represents the ability of homeostatic resilience to withstand perturbations or maintain functions at the current state/phenotype of this individual and (2) phenotypic potential that represents the state/phenotype of the individual on the whole process from health to disease. Here, we proposed a health state manifold (HSM) method derived from dynamic network biomarker method and diffusion map theory to quantify individual health status with the characterization of such two features in a robust and accurate manner based on multi-omics data. To verify our method, HSM method was applied to the quantification of diabetes mellitus (rat subjects) and the Roux-en-Y Gastric Bypass (human subjects) for both disease progression process and recovery process, which demonstrated its effectiveness and potential for personalized medicine and preventive medicine.

Supplementary information: The online version contains supplementary material available at 10.1007/s43657-024-00188-4.

There is evidence that allergic diseases are associated with carcinogenesis. According to translational and epidemiological data, it appears that different cancer types yield different associations. We investigated the relationship between allergic diseases and 28 cancers by Mendelian randomization. Quantitative trait locus analysis was utilized to determine genes expressed in kidney tissue that were affected by allergy-related loci. We further explored the underlying molecular mechanism between allergic diseases and renal cell carcinoma (RCC) with bioinformatics. Of the 28 cancers, evidence suggested that allergies specifically suppressed kidney cancer. Seventy single nucleotide polymorphisms associated with allergic diseases affected the expression of 134 genes in kidney tissue. These 134 genes were enriched in immune-related pathways represented by the major histocompatibility complex class II antigen presentation pathway. Among them, seven core genes were significantly positively correlated with T helper 2 cells. Allergic diseases specifically suppressed RCC through multiple immune pathways. Among them, the major histocompatibility complex class II antigen presentation pathway and T helper 2 cells were the most critical. Our study sheds light on the underlying mechanisms of allergic diseases and RCC and provides therapeutic targets for RCC.

Supplementary information: The online version contains supplementary material available at 10.1007/s43657-025-00229-6.

The intestinal epithelium is continually exposed to food-derived antigens and microbiota. This continual exposure requires a delicate immune homeostasis for food tolerance and protection against infection. Unconventional T lymphocytes, including γδT cells, Natural killer T (NKT) cells, Mucosal-Associated Invariant T (MAIT) cells, and Double-Negative T (DNT) cells, typically reside in the mucosal tissue, such as the colon. These cells play crucial roles in maintaining the integrity of the mucosal barrier and immune homeostasis through cytokine secretion and direct cell-mediated effects. Understanding the proportions and functional status of unconventional T lymphocytes in the colon is crucial for elucidating disease mechanisms. In this study, we developed a 22-color flow cytometry panel for comprehensive immunophenotyping of unconventional T lymphocytes in the murine colon. Our optimized protocol included antibody titration and customized gating strategies. We identified distinct populations of unconventional T lymphocytes, including γδT cells, NKT cells and DNT cells, and compared them with conventional T lymphocyte subsets (CD4⁺ T, CD8αα⁺ T, and CD8αβ⁺ T). We assessed their proliferation, cytotoxicity, cytokine production, and immune checkpoint molecule expression. Inhibitory receptor levels on intraepithelial and lamina propria unconventional T lymphocytes differed, suggesting distinct local environments and regulatory mechanisms. Our findings elucidate the status and function characteristics of unconventional T cells in colonic tissues, providing insights for mechanistic studies and the development of therapies for gastrointestinal diseases.

Supplementary information: The online version contains supplementary material available at 10.1007/s43657-025-00237-6.