circFANCA accelerates the malignant process of OSCC by modulating miR-34a/PA28γ signaling.

Objectives: To investigate the upstream regulatory molecules of proteasomal activator 28γ (PA28γ), and explore its specific regulatory mechanism and potential clinical significance in OSCC.

Materials And Methods: qPCR was used to examine miR-34a, circFANCA and PSME3 expression. Western blotting was adopted to detect PA28γ expression.

Oxidative Stress, Inflammation, Gut Dysbiosis: What Can Polyphenols Do in Inflammatory Bowel Disease?

Inflammatory bowel disease (IBD) is a long-term, progressive, and recurrent intestinal inflammatory disorder. The pathogenic mechanisms of IBD are multifaceted and associated with oxidative stress, unbalanced gut microbiota, and aberrant immune response. Indeed, oxidative stress can affect the progression and development of IBD by regulating the homeostasis of the gut microbiota and immune response.

Engineering MMP-2 Activated Nanoparticles Carrying B7-H3 Bispecific Antibodies for Ferroptosis-Enhanced Glioblastoma Immunotherapy.

Administration of bispecific antibodies (biAbs) in tumor therapy is limited by their short half-life and off-target toxicity. Optimized strategies or targets are needed to overcome these barriers. B7-H3 (CD276), a member of the B7 superfamily, is associated with poor survival in glioblastoma (GBM) patients.

Enhanced nuclear translation is associated with proliferation and progression across multiple cancers.

Recent technological advances have re-invigorated the interest in nuclear translation (NT), but the underlying mechanisms and functional implications of NT remain unknown. Here we show that NT is enhanced in malignant cancer cells and is associated with rapid cell growth. Nuclear ribopuromycylation analyses in a panel of diverse cell lines revealed that NT is scarce in normal immortalized cells, but is ubiquitous and robust in malignant cancer cells.

Proteomics mining of cancer hallmarks on a single-cell resolution.

Dysregulated proteome is an essential contributor in carcinogenesis. Protein fluctuations fuel the progression of malignant transformation, such as uncontrolled proliferation, metastasis, and chemo/radiotherapy resistance, which severely impair therapeutic effectiveness and cause disease recurrence and eventually mortality among cancer patients. Cellular heterogeneity is widely observed in cancer and numerous cell subtypes have been characterized that greatly influence cancer progression.

Modulation of redox homeostasis: A strategy to overcome cancer drug resistance.

Cancer treatment is hampered by resistance to conventional therapeutic strategies, including chemotherapy, immunotherapy, and targeted therapy. Redox homeostasis manipulation is one of the most effective innovative treatment techniques for overcoming drug resistance. Reactive oxygen species (ROS), previously considered intracellular byproducts of aerobic metabolism, are now known to regulate multiple signaling pathways as second messengers.

Heterologous prime-boost immunisation with mRNA- and AdC68-based 2019-nCoV variant vaccines induces broad-spectrum immune responses in mice.

The ongoing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or 2019-nCoV) variants has been associated with the transmission and pathogenicity of COVID-19. Therefore, exploring the optimal immunisation strategy to improve the broad-spectrum cross-protection ability of COVID-19 vaccines is of great significance. Herein, we assessed different heterologous prime-boost strategies with chimpanzee adenovirus vector-based COVID-19 vaccines plus Wuhan-Hu-1 (WH-1) strain (AdW) and Beta variant (AdB) and mRNA-based COVID-19 vaccines plus WH-1 strain (ARW) and Omicron (B.

A Dendrimer Peptide (KK2DP7) Delivery System with Dual Functions of Lymph Node Targeting and Immune Adjuvants as a General Strategy for Cancer Immunotherapy.

The clinical efficacy of personalized cancer vaccines still needs to be improved due to their insufficient immune effect. The development of innovative adjuvants and lymph node-targeted delivery systems is the key to improving the clinical efficacy of personalized vaccines. However, there is still a lack of an adjuvant delivery system that is simple in preparation and capable of mass production and integrates adjuvant and lymph node targeted delivery functions.

Nano-Econazole Enhanced PD-L1 Checkpoint Blockade for Synergistic Antitumor Immunotherapy against Pancreatic Ductal Adenocarcinoma.

Insufficienct T lymphocyte infiltration and unresponsiveness to immune checkpoint blockade therapy are still major difficulties for the clinical treatment of pancreatic ductal adenocarcinoma (PDAC). Although econazole has shown promise in inhibiting PDAC growth, its poor bioavailability and water solubility limit its potential as a clinical therapy for PDAC. Furthermore, the synergistic role of econazole and biliverdin in immune checkpoint blockade therapy in PDAC remains elusive and challenging.

Pharmacological inhibition of EZH2 by ZLD1039 suppresses tumor growth and pulmonary metastasis in melanoma cells in vitro and in vivo.

The incidence and mortality rate of malignant melanoma are increasing worldwide. Metastasis reduces the efficacy of current melanoma therapies and leads to poor prognosis for patients. EZH2 is a methyltransferase that promotes the proliferation, metastasis, and drug resistance of tumor cells by regulating transcriptional activity.

Interleukin-37 promotes DMBA/TPA skin cancer through SIGIRR-mediated inhibition of glycolysis in CD103DC cells.

Interleukin 37 (IL-37), a member of the IL-1 family, is considered a suppressor of innate and adaptive immunity and, hence is a regulator of tumor immunity. However, the specific molecular mechanism and role of IL-37 in skin cancer remain unclear. Here, we report that IL-37b-transgenic mice (IL-37tg) treated with the carcinogenic 7,12-dimethylbenzoanthracene (DMBA)/12-o-tetradecylphorbol-13-acetate (TPA) exhibited enhanced skin cancer and increased tumor burden in the skin by inhibiting the function of CD103 dendritic cells (DCs).

WFDC12-overexpressing contributes to the development of atopic dermatitis via accelerating ALOX12/15 metabolism and PAF accumulation.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by eczema-like skin lesions, dry skin, severe itching, and recurrent recurrence. The whey acidic protein four-disulfide core domain gene WFDC12 is highly expressed in skin tissue and up-regulated in the skin lesions of AD patients, but its role and relevant mechanism in AD pathogenesis have not been studied yet. In this study, we found that the expression of WFDC12 was closely related to clinical symptoms of AD and the severity of AD-like lesions induced by DNFB in transgenic mice.

TSPAN32 suppresses chronic myeloid leukemia pathogenesis and progression by stabilizing PTEN.

We report herein that TSPAN32 is a key node factor for Philadelphia (Ph) leukemia pathogenesis. We found that TSPAN32 expression was repressed by BCR-ABL and ectopic TSPAN32 expression upon Imatinib treatment inhibited the proliferation of Ph cell lines. Tspan32 overexpression significantly prevented BCR-ABL induced leukemia progression in a murine model and impaired leukemia stem cell (LSC) proliferation.

Managing the immune microenvironment of osteosarcoma: the outlook for osteosarcoma treatment.

Osteosarcoma, with poor survival after metastasis, is considered the most common primary bone cancer in adolescents. Notwithstanding the efforts of researchers, its five-year survival rate has only shown limited improvement, suggesting that existing therapeutic strategies are insufficient to meet clinical needs. Notably, immunotherapy has shown certain advantages over traditional tumor treatments in inhibiting metastasis.

Monocytic HLA-DR Expression in Immune Responses of Acute Pancreatitis and COVID-19.

Acute pancreatitis is a common gastrointestinal disease with increasing incidence worldwide. COVID-19 is a potentially life-threatening contagious disease spread throughout the world, caused by severe acute respiratory syndrome coronavirus 2. More severe forms of both diseases exhibit commonalities with dysregulated immune responses resulting in amplified inflammation and susceptibility to infection.

Redox signaling in drug-tolerant persister cells as an emerging therapeutic target.

Drug-tolerant persister (DTP) cells have attracted significant interest, given their predominant role in treatment failure. In this respect, DTP cells reportedly survive after anticancer drug exposure, and their DNA repair mechanisms are altered to enhance adaptive mutation, accounting for the emergence of drug-resistant mutations. DTP cells resume proliferation upon treatment withdrawal and are responsible for cancer relapse.

PHGDH arginine methylation by PRMT1 promotes serine synthesis and represents a therapeutic vulnerability in hepatocellular carcinoma.

Serine synthesis is crucial for tumor growth and survival, but its regulatory mechanism in cancer remains elusive. Here, using integrative metabolomics and transcriptomics analyses, we show a heterogeneity between metabolite and transcript profiles. Specifically, the level of serine in hepatocellular carcinoma (HCC) tissues is increased, whereas the expression of phosphoglycerate dehydrogenase (PHGDH), the first rate-limiting enzyme in serine biosynthesis pathway, is markedly downregulated.

Structural insights into substrate recognition and translocation of human peroxisomal ABC transporter ALDP.

Dysfunctions of ATP-binding cassette, subfamily D, member 1 (ABCD1) cause X-linked adrenoleukodystrophy, a rare neurodegenerative disease that affects all human tissues. Residing in the peroxisome membrane, ABCD1 plays a role in the translocation of very long-chain fatty acids for their β-oxidation. Here, the six cryo-electron microscopy structures of ABCD1 in four distinct conformational states were presented.

Artificial intelligence-assisted selection and efficacy prediction of antineoplastic strategies for precision cancer therapy.

The rapid development of artificial intelligence (AI) technologies in the context of the vast amount of collectable data obtained from high-throughput sequencing has led to an unprecedented understanding of cancer and accelerated the advent of a new era of clinical oncology with a tone of precision treatment and personalized medicine. However, the gains achieved by a variety of AI models in clinical oncology practice are far from what one would expect, and in particular, there are still many uncertainties in the selection of clinical treatment options that pose significant challenges to the application of AI in clinical oncology. In this review, we summarize emerging approaches, relevant datasets and open-source software of AI and show how to integrate them to address problems from clinical oncology and cancer research.

Targeting PSAT1 to mitigate metastasis in tumors with p53-72Pro variant.

The single-nucleotide polymorphism (SNP) of p53, in particular the codon 72 variants, has recently been implicated as a critical regulator in tumor progression. However, the underlying mechanism remains elusive. Here we found that cancer cells carrying codon 72-Pro variant of p53 showed impaired metastatic potential upon serine supplementation.

DOG1 as a novel antibody-drug conjugate target for the treatment of multiple gastrointestinal tumors and liver metastasis.

Discovered On Gastrointestinal stromal tumors protein 1 (DOG1), a major calcium-activated chloride channel, has been used as a common diagnostic marker for gastrointestinal stromal tumors. However, the therapeutic application of DOG1 was not well defined. Here, we aim to investigate its potential as a therapeutic target for an antibody-drug conjugate (ADC) in various cancers of the alimentary tract and metastasis.

Protein persulfidation: Rewiring the hydrogen sulfide signaling in cell stress response.

The past few decades have witnessed significant progress in the discovery of hydrogen sulfide (HS) as a ubiquitous gaseous signaling molecule in mammalian physiology, akin to nitric oxide and carbon monoxide. As the third gasotransmitter, HS is now known to exert a wide range of physiological and cytoprotective functions in the biological systems. However, endogenous HS concentrations are usually low, and its potential biologic mechanisms responsible have not yet been fully clarified.

Intricate confrontation: Research progress and application potential of TRIM family proteins in tumor immune escape.

Background: Tripartite motif (TRIM) family proteins have more than 80 members and are widely found in various eukaryotic cells. Most TRIM family proteins participate in the ubiquitin-proteasome degradation system as E3-ubiquitin ligases; therefore, they play pivotal regulatory roles in the occurrence and development of tumors, including tumor immune escape. Due to the diversity of functional domains of TRIM family proteins, they can extensively participate in multiple signaling pathways of tumor immune escape through different substrates.

Structure-Activity Relationship of Novel Pyrimidine Derivatives with Potent Inhibitory Activities against .

Discovery of novel antitubercular drugs is an effective strategy against drug-resistant tuberculosis (TB). Our previous study has identified as a novel antitubercular compound. Herein, we perform a comprehensive structure-activity relationship (SAR) based on , indicating that the central pyrimidine ring moiety was crucial for the antitubercular activities of its derivatives, and replacing the naphthyl group with hydrophobic substitutes was well tolerated.