Age-related decline in CD8 tissue resident memory T cells compromises antitumor immunity.

Aging compromises antitumor immunity, but the underlying mechanisms remain elusive. Here, we report that aging impairs the generation of CD8 tissue resident memory T (T) cells in nonlymphoid tissues in mice, thus compromising the antitumor activity of aged CD8 T cells, which we also observed in human lung adenocarcinoma. We further identified that the apoptosis regulator BFAR was highly enriched in aged CD8 T cells, in which BFAR suppressed cytokine-induced JAK2 signaling by activating JAK2 deubiquitination, thereby limiting downstream STAT1-mediated T reprogramming.

De novo NAD synthesis contributes to CD8 T cell metabolic fitness and antitumor function.

The dysfunction and clonal constriction of tumor-infiltrating CD8 T cells are accompanied by alterations in cellular metabolism; however, how the cell-intrinsic metabolic pathway specifies intratumoral CD8 T cell features remains elusive. Here, we show that cell-autonomous generation of nicotinamide adenine dinucleotide (NAD) via the kynurenine pathway (KP) contributes to the maintenance of intratumoral CD8 T cell metabolic and functional fitness. De novo NAD synthesis is involved in CD8 T cell metabolism and antitumor function.

USP47 inhibits m6A-dependent c-Myc translation to maintain regulatory T cell metabolic and functional homeostasis.

The functional integrity of Tregs is interwoven with cellular metabolism; however, the mechanisms governing Treg metabolic programs remain elusive. Here, we identified that the deubiquitinase USP47 inhibited c-Myc translation mediated by the RNA N6-methyladenosine (m6A) reader YTHDF1 to maintain Treg metabolic and functional homeostasis. USP47 positively correlated with the tumor-infiltrating Treg signature in samples from patients with colorectal cancer and gastric cancer.

TRAF3/STAT6 axis regulates macrophage polarization and tumor progression.

Converting tumor-associated macrophages (TAMs) from the M2 to the M1 phenotype is considered an effective strategy for cancer therapy. TRAF3 is known to regulate NF-κB signaling. However, the role of TRAF3 in TAM polarization has not yet been completely elucidated.

Comprehensive Analysis and Experimental Validation of a Novel Estrogen/Progesterone-Related Prognostic Signature for Endometrial Cancer.

Estrogen and progesterone are the major determinants of the occurrence and development of endometrial cancer (EC), which is one of the most common gynecological cancers worldwide. Our purpose was to develop a novel estrogen/progesterone-related gene signature to better predict the prognosis of EC and help discover effective therapeutic strategies. We downloaded the clinical and RNA-seq data of 397 EC patients from The Cancer Genome Atlas (TCGA) database.

TRK-fused gene (TFG) regulates ULK1 stability via TRAF3-mediated ubiquitination and protects macrophages from LPS-induced pyroptosis.

TRK-fused gene (TFG) is known to be involved in protein secretion and plays essential roles in an antiviral innate immune response. However, its function in LPS-induced inflammation and pyroptotic cell death is still unknown. Here, we reported that TFG promotes the stabilization of Unc-51 like autophagy activating kinase (ULK1) and participates in LPS plus nigericin (Ng) induced pyroptotic cell death.

Protein Tyrosine Kinase 7 Regulates EGFR/Akt Signaling Pathway and Correlates With Malignant Progression in Triple-Negative Breast Cancer.

Purpose: Triple-negative breast cancer (TNBC), the most aggressive subtype of breast cancer, is associated with high invasiveness, high metastatic occurrence and poor prognosis. Protein tyrosine kinase 7 (PTK7) plays an important role in multiple cancers. However, the role of PTK7 in TNBC has not been well addressed.

Transcriptional network constituted of CBP, Ku70, NOX2, and BAX prevents the cell death of necrosis, paraptosis, and apoptosis in human melanoma.

CREB-binding protein (CBP) is an acetyltransferase known to play multiple roles in the transcriptions of genes involving oxidative metabolism, cell cycle, DNA damage checkpoints, and cell death. In this study, CBP was found to positively regulate the expression of Ku70, and both CBP and Ku70 were found to negatively regulate the expression of NOX2, therefore, mitigating the intracellular ROS in human melanoma. Knocking down CBP or Ku70 induced necrotic and paraptotic cell death as indicated by high-level intracellular ROS, cytoplasmic vacuolization, and cell cycle arrest in the S phase.

SP1-induced upregulation of lncRNA CTBP1-AS2 accelerates the hepatocellular carcinoma tumorigenesis through targeting CEP55 via sponging miR-195-5p.

As reported in many research, LncRNA CTBP1 divergent transcript (CTBP1-AS2) remarkably affects the progression of several tumors. However, the precise role and function of CTBP1-AS2 in hepatocellular carcinoma (HCC) remained unknown. We found that CTBP1-AS2 expressions were increased in HCC samples and cells.

Salvia miltiorrhiza-Derived Sal-miR-58 Induces Autophagy and Attenuates Inflammation in Vascular Smooth Muscle Cells.

Autophagy is associated with the cytoprotection of physiological processes against inflammation and oxidative stress. Salvia miltiorrhiza possesses cardiovascular protective actions and has powerful anti-oxidative and anti-inflammatory effects; however, whether and how Salvia miltiorrhiza-derived microRNAs (miRNAs) protect vascular smooth muscle cells (VSMCs) by inducing autophagy across species are unknown. We first screened and identified Sal-miR-58 from Salvia miltiorrhiza as a natural autophagy inducer.

Tanshinone ⅡA inhibits VSMC inflammation and proliferation in vivo and in vitro by downregulating miR-712-5p expression.

The inflammation and proliferation of vascular smooth muscle cells (VSMCs) are the basic pathological feature of proliferative vascular diseases. Tanshinone ⅡA (Tan ⅡA), which is the most abundant fat-soluble element extracted from Salvia miltiorrhiza, has potent protective effects on the cardiovascular system. However, the underlying mechanism is still not fully understood.

TRAF3 promotes ROS production and pyroptosis by targeting ULK1 ubiquitination in macrophages.

Disrupted mitochondrial function and reactive oxygen species (ROS) generation cause cellular damage and oxidative stress-induced macrophage inflammatory cell death. It remains unclear how mitochondrial dysfunction relates to inflammasome activation and pyroptotic cell death. In this study, we demonstrated that tumor necrosis factor receptor-associated factor 3 (TRAF3) regulates mitochondrial ROS production and promotes TLR agonist LPS plus nigericin (LPS/Ng)-induced inflammasome and pyroptosis in mouse primary macrophages and human monocyte THP-1 cells.

Upregulation of OTUD7B (Cezanne) Promotes Tumor Progression via AKT/VEGF Pathway in Lung Squamous Carcinoma and Adenocarcinoma.

OTUD7B, a multifunctional deubiquitinylase, plays an essential role in inflammation and proliferation signals. However, its function in lung cancer remains largely unknown. The aim of this study was to evaluate the prognostic significance of OTUD7B in patients with lung adenocarcinoma and squamous carcinoma and to characterize its molecular mechanisms in lung cancer progression and metastasis.

Ambient temperature-mediated enzymic activities and intestinal microflora in Lymantria dispar larvae.

To understand how ambient temperature affect the gypsy moth larvae, and provide a theoretical basis for pest control in different environments. Fourth instar gypsy moth larvae were incubating for 3 hr at 15℃, 20℃, 25℃, 30℃, 35℃, and 40℃, respectively. Afterward, digestive and antioxidant enzyme activities, total antioxidant capacity, and intestinal microflora community were analyzed to reveal how the caterpillars respond to ambient temperature stress.

Triphenylethylene-Coumarin Hybrid TCH-5c Suppresses Tumorigenic Progression in Breast Cancer Mainly Through the Inhibition of Angiogenesis.

Background: Coumarins are a wide group of naturally occurring compounds which exhibit a wide range of biological properties such as anti-cancer activities. Here, we characterized the biological functions of three Triphenylethylene-Coumarin Hybrids (TCHs) both in cell culture and nude mouse model.

Methods: Cell proliferation assay was performed in the cell cultures of both EA.

Primary extra-nodal non-Hodgkin lymphoma in buttock soft tissue: A rare case report.

Rationale: Primary extra-nodal non-Hodgkin lymphoma (PE-NHL) arising in the region of the buttocks is rare. After reviewing the literature from the last 20 years, we found only 3 reported lymphomas originating from soft tissue of the buttocks. In our case, positron emission tomography/computed tomography (PET/CT) was performed for the first time, both before and after treatment, to determine the initial stage of PE-NHL and the curative effects of treatment.

Tumor Necrosis Factor Receptor-Associated Factor Regulation of Nuclear Factor κB and Mitogen-Activated Protein Kinase Pathways.

Tumor necrosis factor receptor (TNFR)-associated factors (TRAFs) are a family of structurally related proteins that transduces signals from members of TNFR superfamily and various other immune receptors. Major downstream signaling events mediated by the TRAF molecules include activation of the transcription factor nuclear factor κB (NF-κB) and the mitogen-activated protein kinases (MAPKs). In addition, some TRAF family members, particularly TRAF2 and TRAF3, serve as negative regulators of specific signaling pathways, such as the noncanonical NF-κB and proinflammatory toll-like receptor pathways.

Overexpression of YB1 C-terminal domain inhibits proliferation, angiogenesis and tumorigenicity in a SK-BR-3 breast cancer xenograft mouse model.

Y-box-binding protein 1 (YB1) is a multifunctional transcription factor with vital roles in proliferation, differentiation and apoptosis. In this study, we have examined the role of its C-terminal domain (YB1 CTD) in proliferation, angiogenesis and tumorigenicity in breast cancer. Breast cancer cell line SK-BR-3 was infected with GFP-tagged YB1 CTD adenovirus expression vector.

The Role of the Y Box Binding Protein 1 C-Terminal Domain in Vascular Endothelial Cell Proliferation, Apoptosis, and Angiogenesis.

Different domains of the multifunctional transcription factor Y-box binding protein 1 (YB1) regulate proliferation, differentiation, and apoptosis by transactivating or repressing the promoters of various genes. Here we report that the C-terminal domain of YB1 (YB1 CTD) is involved in endothelial cell proliferation, apoptosis, and tube formation. The oligo pull-down assays demonstrated that YB1 directly binds double-stranded GC box sequences in endothelial cells through the 125-220 amino acids.

TCR signaling to NF-κB and mTORC1: Expanding roles of the CARMA1 complex.

Naïve T-cell activation requires signals from both the T-cell receptor (TCR) and the costimulatory molecule CD28. A central mediator of the TCR and CD28 signals is the scaffold protein CARMA1, which functions by forming a complex with partner proteins, Bcl10 and MALT1. A well-known function of the CARMA1 signaling complex is to mediate activation of IκB kinase (IKK) and its target transcription factor NF-κB, thereby promoting T-cell activation and survival.