Targeted demethylation of the SLC5A7 promotor inhibits colorectal cancer progression.

Background: SLC5A7 (solute carrier family 5 member 7), also known as choline transporter 1 (CHT1), is downregulated in colorectal cancer (CRC) and functions as a tumor suppressor. However, the mechanisms underlying the inactivation of SLC5A7 in CRC remain to be elucidated.

Results: In the present study, two broad-spectrum demethylation agents (azacitidine and decitabine) employed to treat CRC cells significantly upregulated SLC5A7 expression.

Mitochondrial adaptation in cancer drug resistance: prevalence, mechanisms, and management.

Drug resistance represents a major obstacle in cancer management, and the mechanisms underlying stress adaptation of cancer cells in response to therapy-induced hostile environment are largely unknown. As the central organelle for cellular energy supply, mitochondria can rapidly undergo dynamic changes and integrate cellular signaling pathways to provide bioenergetic and biosynthetic flexibility for cancer cells, which contributes to multiple aspects of tumor characteristics, including drug resistance. Therefore, targeting mitochondria for cancer therapy and overcoming drug resistance has attracted increasing attention for various types of cancer.

Autophagy in health and disease: From molecular mechanisms to therapeutic target.

Macroautophagy/autophagy is an evolutionally conserved catabolic process in which cytosolic contents, such as aggregated proteins, dysfunctional organelle, or invading pathogens, are sequestered by the double-membrane structure termed autophagosome and delivered to lysosome for degradation. Over the past two decades, autophagy has been extensively studied, from the molecular mechanisms, biological functions, implications in various human diseases, to development of autophagy-related therapeutics. This review will focus on the latest development of autophagy research, covering molecular mechanisms in control of autophagosome biogenesis and autophagosome-lysosome fusion, and the upstream regulatory pathways including the AMPK and MTORC1 pathways.

Repurposing Oxiconazole against Colorectal Cancer via PRDX2-mediated Autophagy Arrest.

Colorectal cancer (CRC) is one of the most common malignancies worldwide, yet successful treatment still remains a challenge. In this study, we found that oxiconazole (OXI), a broad-spectrum antifungal agent, exhibits certain anti-tumor effect against CRC. Autophagy arrest and subsequent apoptosis are characterized as pivotal events involving OXI-induced growth suppression of CRC cells.

Combining intramuscular and intranasal homologous prime-boost with a chimpanzee adenovirus-based COVID-19 vaccine elicits potent humoral and cellular immune responses in mice.

The efficacy of many coronavirus disease 2019 (COVID-19) vaccines has been shown to decrease to varying extents against new severe acute respiratory syndrome coronavirus 2 variants, which are responsible for the continuing COVID-19 pandemic. Combining intramuscular and intranasal vaccination routes is a promising approach for achieving more potent immune responses. We evaluated the immunogenicity of prime-boost protocols with a chimpanzee adenovirus serotype 68 vector-based vaccine, ChAdTS-S, administered via both intranasal and intramuscular routes in BALB/c mice.

Erratum: Author correction to "Development of small-molecule tropomyosin receptor kinase (TRK) inhibitors for NTRK fusion cancers" [Acta Pharmaceutica Sinica B 11 (2021) 355-372].

[This corrects the article DOI: 10.1016/j.apsb.

A BRD4 PROTAC nanodrug for glioma therapy the intervention of tumor cells proliferation, apoptosis and M2 macrophages polarization.

Glioma is a primary aggressive brain tumor with high recurrence rate. The poor efficiency of chemotherapeutic drugs crossing the blood‒brain barrier (BBB) is well-known as one of the main challenges for anti-glioma therapy. Moreover, massive infiltrated tumor-associated macrophages (TAMs) in glioma further thwart the drug efficacy.

Differentiation of Bone Mesenchymal Stem Cells Into Vascular Endothelial Cell-Like Cells Using Functionalized Single-Walled Carbon Nanotubes.

Carbon nanotubes (CNTs) are a promising bioactive scaffold for bone regeneration because of their superior mechanical and biological properties. Vascularization is crucial in bone tissue engineering, and insufficient vascularization is a long-standing problem in tissue-engineered scaffolds. However, the effect of CNTs on vascularization is still minimal.

Antioxidant Therapy in Cancer: Rationale and Progress.

Cancer is characterized by increased oxidative stress, an imbalance between reactive oxygen species (ROS) and antioxidants. Enhanced ROS accumulation, as a result of metabolic disturbances and signaling aberrations, can promote carcinogenesis and malignant progression by inducing gene mutations and activating pro-oncogenic signaling, providing a possible rationale for targeting oxidative stress in cancer treatment. While numerous antioxidants have demonstrated therapeutic potential, their clinical efficacy in cancer remains unproven.

Harnessing redox signaling to overcome therapeutic-resistant cancer dormancy.

Dormancy occurs when cells preserve viability but stop proliferating, which is considered an important cause of tumor relapse, which may occur many years after clinical remission. Since the life cycle of dormant cancer cells is affected by both intracellular and extracellular factors, gene mutation or epigenetic regulation of tumor cells may not fully explain the mechanisms involved. Recent studies have indicated that redox signaling regulates the formation, maintenance, and reactivation of dormant cancer cells by modulating intracellular signaling pathways and the extracellular environment, which provides a molecular explanation for the life cycle of dormant tumor cells.

Extracellular Vesicles: Recent Insights Into the Interaction Between Host and Pathogenic Bacteria.

Extracellular vesicles (EVs) are nanosized lipid particles released by virtually every living cell. EVs carry bioactive molecules, shuttle from cells to cells and transduce signals, regulating cell growth and metabolism. Pathogenic bacteria can cause serious infections via a wide range of strategies, and host immune systems also develop extremely complex adaptations to counteract bacterial infections.

CircRFWD3 promotes HNSCC metastasis by modulating miR-27a/b/PPARγ signaling.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer in the world, the 5-year survival rate of patients with HNSCC is still about 50% due to frequent metastasis and recurrence. Circular RNAs (circRNAs) have been characterized as key regulators of gene expression in numerous malignancies. However, the role of circRNA in HNSCC metastasis remains largely unknown.

The Safety and Feasibility of Laparoscopic Gastrectomy after Neoadjuvant Chemotherapy for Locally Advanced Gastric Cancer.

Background: Neoadjuvant chemotherapy is incrementally applied to remedy locally advanced gastric cancer. However, NACT also enhances the difficulty of laparoscopic lymph node dissection. The objective of our study was to evaluate the safety and feasibility of laparoscopic gastrectomy for locally advanced gastric cancer after neoadjuvant chemotherapy.

A cellular thermal shift assay for detecting amino acid sites involved in drug target engagement.

Evaluating how drugs bind to specific targets at the cellular level is essential to their development and efficacy. Here, we present a protocol to detect the amino acid sites involved in drug-target engagement using a cellular thermal shift assay, which is based on ligand-induced protein thermal stabilization. We also describe generation of cell lines expressing wild-type or mutated target protein and drug treatment.

Subinhibitory Cefotaxime and Levofloxacin Concentrations Contribute to Selection of Pseudomonas aeruginosa in Coculture with Staphylococcus aureus.

Bacterial species in the polymicrobial community evolve interspecific interaction relationships to adapt to the survival stresses imposed by neighbors or environmental cues. Pseudomonas aeruginosa and Staphylococcus aureus are two common bacterial pathogens frequently coisolated from patients with burns and respiratory disease. Whether the application of commonly used antibiotics influences the interaction dynamics of the two species still remains largely unexplored.

ROS generation attenuates the anti-cancer effect of CPX on cervical cancer cells by inducing autophagy and inhibiting glycophagy.

Cervical cancer is one of the most common gynecological malignancies with poor prognosis due to constant chemoresistance and repeated relapse. Ciclopirox olamine (CPX), a synthetic antifungal agent, has recently been identified to be a promising anti-cancer candidate. However, the detailed mechanisms related to its anti-cancer effects remain unclear and need to be further elucidated.

A minimalist and robust chemo-photothermal nanoplatform capable of augmenting autophagy-modulated immune response against breast cancer.

Previously used in anti-fungal therapy, itraconazole has now been shown to be successful in treating advanced breast cancer (NCT00798135). However, its poor solubility still restricts its application in clinical treatment. There is therefore an urgent need for combined methods to enhance the therapeutic effect of itraconazole (IC) in breast cancer treatment.

Bioinspired and Biomimetic Nanomedicines for Targeted Cancer Therapy.

Undesirable side effects and multidrug resistance are the major obstacles in conventional chemotherapy towards cancers. Nanomedicines provide alternative strategies for tumor-targeted therapy due to their inherent properties, such as nanoscale size and tunable surface features. However, the applications of nanomedicines are hampered in vivo due to intrinsic disadvantages, such as poor abilities to cross biological barriers and unexpected off-target effects.

Oxidative Stress in Cancer Immunotherapy: Molecular Mechanisms and Potential Applications.

Immunotherapy is an effective treatment option that revolutionizes the management of various cancers. Nevertheless, only a subset of patients receiving immunotherapy exhibit durable responses. Recently, numerous studies have shown that oxidative stress induced by reactive oxygen species (ROS) plays essential regulatory roles in the tumor immune response, thus regulating immunotherapeutic effects.

The Emerging Roles and Therapeutic Implications of Epigenetic Modifications in Ovarian Cancer.

Ovarian cancer (OC) is one of the most lethal gynecologic malignancies globally. In spite of positive responses to initial therapy, the overall survival rates of OC patients remain poor due to the development of drug resistance and consequent cancer recurrence. Indeed, intensive studies have been conducted to unravel the molecular mechanisms underlying OC therapeutic resistance.

A specific upregulated long noncoding RNA in colorectal cancer promotes cancer progression.

Long noncoding RNA (lncRNA) plays a crucial role in the pathogenesis of various diseases, including colorectal cancer (CRC). The gene mutations of adenomatous polyposis coli (APC) were found in most patients with CRC. They function as important inducers of tumorigenesis.