Targeting MAPK14 by Lobeline Upregulates Slurp1-Mediated Inhibition of Alternative Activation of TAM and Retards Colorectal Cancer Growth.

Colorectal cancer (CRC) usually creates an immunosuppressive microenvironment, thereby hindering immunotherapy response. Effective treatment options remain elusive. Using scRNA-seq analysis in a tumor-bearing murine model, it is found that lobeline, an alkaloid from the herbal medicine lobelia, promotes polarization of tumor-associated macrophages (TAMs) toward M1-like TAMs while inhibiting their polarization toward M2-like TAMs.

Human urinary occurrence of thiourea vulcanization accelerators and their human exposure.

Thiourea vulcanization accelerators (TVAs) have been detected in various household dust samples, indicating their widespread human exposure. Until now, the occurrence of TVAs in human urine, a suitable matrix for assessing human exposure, has remained unknown. The present study comprehensively examined eight kinds of TVAs in urine samples (n = 277) from participants living in Taizhou, China.

Presence of N, N'-Substituted p-Phenylenediamine-Derived Quinones in Human Urine.

Human exposure to various N,N'-substituted p-phenylenediamine-derived quinones (PPDQs) has been of increasing concern. Recent studies have examined N-phenyl-N'-(1,3-dimethylbutyl)-p-phenylenediamine-derived quinone (6PPDQ) in human urine to evaluate human exposure. However, other PPDQs in human urine have not been thoroughly investigated.

UBE2M forms a positive feedback loop with estrogen receptor to drive breast cancer progression and drug resistance.

UBE2M, a NEDD8-conjugating enzyme, is dysregulated in various human cancers and promotes tumor cell proliferation. However, its role in estrogen receptor-positive (ER) breast cancer remains unknown. We found that UBE2M expression was significantly higher in ER breast cancer tissues than in ER-negative (ER) breast cancer tissues.

Er:YAG laser therapy in combination with GLUMA desensitizer reduces dentin hypersensitivity in children with molar-incisor hypomineralization: a randomized clinical trial.

This study aimed to investigate the effectiveness of erbium-doped yttrium garnet (Er:YAG) laser and GLUMA desensitizer for dentin hypersensitivity in teeth affected by Molar-Incisor Hypomineralization (MIH). One hundred twenty children were randomly allocated to four groups: the control (Co) group, the desensitizer (De) group, the laser (La) group, and the laser + desensitizer (La + De) group. Outcome measures included Visual Analogue Scale (VAS) and 14-item Oral Health Impact Profile (OHIP-14) evaluation.

Effects of different signaling pathways on odontogenic differentiation of dental pulp stem cells: a review.

Dental pulp stem cells (DPSCs) are a type of mesenchymal stem cells that can differentiate into odontoblast-like cells and protect the pulp. The differentiation of DPSCs can be influenced by biomaterials or growth factors that activate different signaling pathways or . In this review, we summarized six major pathways involved in the odontogenic differentiation of DPSCs, Wnt signaling pathways, Smad signaling pathways, MAPK signaling pathways, NF-kB signaling pathways, PI3K/AKT/mTOR signaling pathways, and Notch signaling pathways.

BPDE-DNA adduct formation and alterations of mRNA, protein, and DNA methylation of CYP1A1, GSTP1, and GSTM1 induced by benzo[a]pyrene and the intervention of aspirin in mice.

Benzo[a]pyrene (B[a]P), one typical environmental pollutant, the toxicity mechanisms, and potential prevention remain perplexing. Available evidence suggests cytochrome P450 1A1 (CYP1A1) and glutathione S-transferases (GSTs) metabolize B[a]P, resulting in metabolic activation and detoxification of B[a]P. This study aimed to reveal the impact of B[a]P exposure on trans-7,8-diol-anti-9,10-epoxide DNA (BPDE-DNA) adduct formation, level of CYP1A1, glutathione S-transferase pi (GSTP1) and glutathione S-transferase mu1 (GSTM1) mRNA, protein and DNA methylation in mice, and the potential prevention of aspirin (ASP).

Single-cell analyses reveal cannabidiol rewires tumor microenvironment via inhibiting alternative activation of macrophage and synergizes with anti-PD-1 in colon cancer.

Colorectal tumors often create an immunosuppressive microenvironment that prevents them from responding to immunotherapy. Cannabidiol (CBD) is a non-psychoactive natural active ingredient from the cannabis plant that has various pharmacological effects, including neuroprotective, antiemetic, anti-inflammatory, and antineoplastic activities. This study aimed to elucidate the specific anticancer mechanism of CBD by single-cell RNA sequencing (scRNA-seq) and single-cell ATAC sequencing (scATAC-seq) technologies.

Upregulation of hsa_circ_0002003 promotes hepatocellular carcinoma progression.

Background: Circular RNAs (circRNAs), which are involved in various human malignancies, have emerged as promising biomarkers. The present study aimed to investigate unique expression profiles of circRNAs in hepatocellular carcinoma (HCC) and identify novel biomarkers associated with HCC development and progression.

Methods: CircRNA expression profiles of HCC tissues were jointly analyzed to identify differentially expressed circRNAs.

Nimbolide Exhibits Potent Anticancer Activity Through ROS-Mediated ER Stress and DNA Damage in Human Non-small Cell Lung Cancer Cells.

The non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancers. It is usually diagnosed at an advanced stage with poor prognosis. Nimbolide (NB), a terpenoid limonoid isolated from the flowers and leaves of neem tree, possesses anticancer properties in various cancer cell lines.

NEDD8-conjugating enzyme E2s: critical targets for cancer therapy.

NEDD8-conjugating enzymes, E2s, include the well-studied ubiquitin-conjugating enzyme E2 M (UBE2M) and the poorly characterized ubiquitin-conjugating enzyme E2 F (UBE2F). UBE2M and UBE2F have distinct and prominent roles in catalyzing the neddylation of Cullin or non-Cullin substrates. These enzymes are overexpressed in various malignancies, conferring a worse overall survival.

Targeting cathepsin B by cycloastragenol enhances antitumor immunity of CD8 T cells via inhibiting MHC-I degradation.

Background: The loss of tumor antigens and depletion of CD8 T cells caused by the PD-1/PD-L1 pathway are important factors for tumor immune escape. In recent years, there has been increasing research on traditional Chinese medicine in tumor treatment. Cycloastragenol (CAG), an effective active molecule in , has been found to have antiviral, anti-aging, anti-inflammatory, and other functions.

Neddylation pathway promotes myeloid-derived suppressor cell infiltration via NF-κB-mCXCL5 signaling in lung cancer.

Myeloid-derived suppressor cells (MDSCs), a population derived from immature myeloid progenitors, are present in the tumors of patients and highly protumorigenic. However, the molecular mechanisms regulating MDSC infiltration remain unclear. Neddylation pathway is overactivated in multiple cancers and has a significant role in tumor progression.

MilR3, a unique SARP family pleiotropic regulator in Streptomyces bingchenggensis.

Streptomyces bingchenggensis is the main industrial producer of milbemycins, which are a group of 16-membered macrocylic lactones with excellent insecticidal activities. In the past several decades, scientists have made great efforts to solve its low productivity. However, a lack of understanding of the regulatory network of milbemycin biosynthesis limited the development of high-producing strains using a regulatory rewiring strategy.

Targeting protein phosphatases for the treatment of inflammation-related diseases: From signaling to therapy.

Inflammation is the common pathological basis of autoimmune diseases, metabolic diseases, malignant tumors, and other major chronic diseases. Inflammation plays an important role in tissue homeostasis. On one hand, inflammation can sense changes in the tissue environment, induce imbalance of tissue homeostasis, and cause tissue damage.

Integrated Analysis Highlights the Immunosuppressive Role of TREM2 Macrophages in Hepatocellular Carcinoma.

Recently, attention has been focused on the central role of TREM2 in diverse pathologies. However, the role of TREM2 signaling in the tumor microenvironment of hepatocellular carcinoma (HCC) remains poorly understood. Herein, we systematically investigated the single-cell transcriptomes of human HCC tissues and found that was predominantly expressed by a macrophage subpopulation enriched in tumor tissues that resemble lipid-associated macrophages (LAMs).

Immune-related lincRNA pairs predict prognosis and therapeutic response in hepatocellular carcinoma.

Growing evidence has demonstrated the functional relevance of long intergenic noncoding RNAs (lincRNAs) to tumorigenesis and immune response. However, immune-related lincRNAs and their value in predicting the clinical outcomes of patients with liver cancer remain largely unexplored. Herein, we utilized the strategy of iterative gene pairing to construct a tumor-specific immune-related lincRNA pairs signature (IRLPS), which did not require specific expression levels, as an indicator of patient outcomes.

Species-resolved sequencing of low-biomass or degraded microbiomes using 2bRAD-M.

Microbiome samples with low microbial biomass or severe DNA degradation remain challenging for amplicon-based or whole-metagenome sequencing approaches. Here, we introduce 2bRAD-M, a highly reduced and cost-effective strategy which only sequences ~ 1% of metagenome and can simultaneously produce species-level bacterial, archaeal, and fungal profiles. 2bRAD-M can accurately generate species-level taxonomic profiles for otherwise hard-to-sequence samples with merely 1 pg of total DNA, high host DNA contamination, or severely fragmented DNA from degraded samples.

Particle-Based Calculation and Visualization of Protein Cavities Using SES Models.

The analysis of molecular cavities, where ligands interact with protein structures, plays a critical role in protein structure-based drug design. However, it is a challenge because of the ambiguous definition of the cavity boundaries in most cavity detection methods. The cavities are mostly calculated by input parameters, which are difficult for users to visualize cavities in interactive ways.

Elevated Neddylation Pathway Promotes Th2 Cells Infiltration by Transactivating STAT5A in Hepatocellular Carcinoma.

Neddylation is a process in which a ubiquitin-like molecule NEDD8 is conjugated to a lysine residue of the substrate protein successive enzymatic cascade reactions. Inactivation of neddylation pathway triggers tumor cell apoptosis or senescence to suppress the tumor growth. So far, there has been limited research on the role of the neddylation pathway (NEDD8-UBE2M-RBX1 axis) in the immune response.

Epigenetically associated CCL20 upregulation correlates with esophageal cancer progression and immune disorder.

Chemokines have distinct effects on tumor progression by affecting cancer immunity and tumorigenesis. However, the characteristic chemokine profiles and their roles in immune cell recruitment and cancer cell biology are not entirely understood in esophageal cancer. Here, we scrutinized chemokine's expression profiles in independent esophageal cancer cohorts and identified the elevated CCL20 as a risk factor to predict patients' prognosis regardless of histology subtypes.

NEDD8-conjugating enzyme E2 UBE2F confers radiation resistance by protecting lung cancer cells from apoptosis.

Lung cancer, which is exacerbated by environmental pollution and tobacco use, has become the most common cause of cancer-related deaths worldwide, with a five-year overall survival rate of only 19% (Siegel et al., 2020; Yang et al., 2020; Yu and Li, 2020).