A precision intelligent nanomissile for inhibiting tumor metastasis, boosting energy deprivation and immunotherapy.

The epithelial-mesenchymal transition (EMT), tumor stroma and local metabolic alterations cooperate to establish a unique tumor microenvironment (TME) that fosters tumor progression and metastasis. To tackle this challenge, a precision intelligent nanomissile named HA@AT-Pd has been designed for dual-pronged cancer-associated fibroblast (CAF) transformation and tumor cell elimination. It is observed that HA@AT-Pd inhibits the production of cancer stem cells (CSCs) by blocking the TGF-β/Smad signaling pathway-mediated EMT and reversing activated CAFs to quiescence.

3D Chromatin Alteration by Disrupting β-Catenin/CBP Interaction Is Enriched with Insulin Signaling in Pancreatic Cancer.

The therapeutic potential of targeting the β-catenin/CBP interaction has been demonstrated in a variety of preclinical tumor models with a small molecule inhibitor, ICG-001, characterized as a β-catenin/CBP antagonist. Despite the high binding specificity of ICG-001 for the N-terminus of CBP, this β-catenin/CBP antagonist exhibits pleiotropic effects. Our recent studies found global changes in three-dimensional (3D) chromatin architecture in response to disruption of the β-catenin/CBP interaction in pancreatic cancer cells.

Reprogramming of 3D chromatin domains by antagonizing the β-catenin/CBP interaction attenuates insulin signaling in pancreatic cancer.

The therapeutic potential of targeting the β-catenin/CBP interaction has been demonstrated in a variety of preclinical tumor models with a small molecule inhibitor, ICG-001, characterized as a β-catenin/CBP antagonist. Despite the high binding specificity of ICG-001 for the N-terminus of CBP, this β-catenin/CBP antagonist exhibits pleiotropic effects. Our recent studies found global changes in three-dimensional (3D) chromatin architecture in response to disruption of the β-catenin/CBP interaction in pancreatic cancer cells.

A pro-death autophagy-based nanoplatform for enhancing antitumour efficacy with improved immune responses.

Due to the pro-survival effect of mild autophagy, the therapeutic effect of chemo-immunotherapy is unsatisfactory. In addition, the adverse tumour microenvironment (TME), including the lack of antigen presentation, the deficiency of oxygen supply and immunosuppressive cells, results in immune escape and metastasis. Herein, a novel nanoplatform (CS-3BP/PA@DOX) based on the autophagy cascade is proposed for the first time to deliver the chemotherapeutic doxorubicin (DOX) and respiration inhibitor 3-bromopyruvic acid (3BP) to overcome the above obstacles.

An active transport dual adaptive nanocarrier designed to overcome the corneal microenvironment for neovascularization therapy.

The eyes have a complicated microenvironment with many clearance mechanisms, making it challenging for effective drug delivery to the targeted areas of the eyes. Substrate transport mediated by active transporters is an important way to change drug metabolism in the ocular microenvironment. We designed multifunctional, dual-adaptive nanomicelles (GSCQ@NTB) which could overcome multiple physiological barriers by acting on both the efflux transporter and influx transporter to achieve deep delivery of the P-gp substrate in the cornea.

A dual-sensitive nanoparticle-mediated deepening synergistic therapy strategy involving DNA damage and ICD stimuli to treat triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is one of the most aggressive cancers with an immunosuppressive microenvironment, and achieving a satisfactory effect from monotherapies, such as chemotherapy, photodynamic therapy (PDT) or immunotherapy, remains difficult. To solve this puzzle, a deepening synergistic therapy strategy of DNA damage and immunogenic cell death (ICD) stimuli was proposed. We engineered a doxorubicin (DOX) and 4-(hydroxymethyl) phenylboronic acid pinacol ester (PBAP) prodrug polymer, and encapsulated chlorin e6 (Ce6) to obtain the hyaluronidase (HAase) and HO dual-sensitive responsive nanoparticles (Ce6/HDP NPs).

A Vanadium-Based Nanoplatform Synergizing Ferroptotic-like Therapy with Glucose Metabolism Intervention for Enhanced Cancer Cell Death and Antitumor Immunity.

Ferroptosis activation has been considered a mighty weapon for cancer treatment, and growing attention is being paid to reinforcing tumor cells' sensitivity to ferroptosis. However, the existence of certain ferroptosis resistance mechanisms, especially the abnormal metabolism of tumor cells, has long been underestimated. We propose an enhanced ferroptosis-activating pattern via regulating tumor cells' glycometabolism and construct a nanoplatform named PMVL, which is composed of lonidamine (LND)-loaded tannic acid coordinated vanadium oxides with the camouflage of PD-L1 inhibiting peptide-modified tumor cell membrane.

Zn-doped chitosan/alginate multilayer coatings on porous hydroxyapatite scaffold with osteogenic and antibacterial properties.

Porous hydroxyapatite (HA) scaffolds prepared by three-dimensional (3D) printing have wide application prospects owing to personalized structural design and excellent biocompatibility. However, the lack of antimicrobial properties limits its widespread use. In this study, a porous ceramic scaffold was fabricated by digital light processing (DLP) method.

Research progress of exosomes as drug carriers in cancer and inflammation.

Extracellular vesicles (EVs) could be produced by most cells and play an important role in disease development. As a subtype of EVs, exosomes exhibit suitable size, rich surface markers and diverse contents, making them more appealing as potential drug carriers. Compared with traditional synthetic nanoparticles, exosomes possess superior biocompatibility and much lower immunogenicity.

Oxygen-boosted biomimetic nanoplatform for synergetic phototherapy/ferroptosis activation and reversal of immune-suppressed tumor microenvironment.

Photodynamic therapy (PDT) induces apoptosis of cancer cells by generating cytotoxic reactive oxygen species, the therapeutic effect of which, however, is impeded by intrinsic/inducible apoptosis-resistant mechanisms in cancer cells and hypoxia of tumor microenvironment (TME); also, PDT-induced anti-tumor immunity activation is insufficient. To deal with these obstacles, a novel biomimetic nanoplatform is fabricated for the precise delivery of photosensitizer chlorin e6 (Ce6), hemin and PEP20 (CD47 inhibitory peptide), integrating oxygen-boosted PDT, ferroptosis activation and CD47-SIRPα blockade. Hemin's catalase-mimetic activity alleviates TME hypoxia and enhances PDT.

NUPR1 promotes the proliferation and metastasis of oral squamous cell carcinoma cells by activating TFE3-dependent autophagy.

Oral squamous cell carcinoma (OSCC) is the most common type of oral malignancy, and metastasis accounts for the poor prognosis of OSCC. Autophagy is considered to facilitate OSCC development by mitigating various cellular stresses; nevertheless, the mechanisms of autophagy in OSCC cell proliferation and metastasis remain unknown. In our study, high-sensitivity label-free quantitative proteomics analysis revealed nuclear protein 1 (NUPR1) as the most significantly upregulated protein in formalin-fixed paraffin-embedded tumour samples derived from OSCC patients with or without lymphatic metastasis.

3D-printed composite, calcium silicate ceramic doped with CaSO4·2H2O: Degradation performance and biocompatibility.

Calcium silicate is a common implant material with excellent mechanical strength and good biological activity. In recent years, the addition of strengthening materials to calcium silicate has been proven to promote bone tissue regeneration, but its degradation properties require further improvements. In this paper, calcium silicate was used as the matrix, and 10 wt% hydroxyapatite and 10 wt% strontium phosphate were added to im prove the biological activity of the scaffold.

Exosome-derived long non-coding RNA ADAMTS9-AS2 suppresses progression of oral submucous fibrosis via AKT signalling pathway.

Oral submucosal fibrosis (OSF) is one of the pre-cancerous lesions of oral squamous cell carcinoma (OSCC). Its malignant rate is increasing, but the mechanism of malignancy is not clear. We previously have elucidated the long non-coding RNA (lncRNA) expression profile during OSF progression at the genome-wide level.

The 3D genomic landscape of differential response to EGFR/HER2 inhibition in endocrine-resistant breast cancer cells.

Background: Recent studies suggested that crosstalk between ERα and EGFR/HER2 pathways plays a critical role in mediating endocrine therapy resistance. Several inhibitors targeting EGFR/HER2 signaling, including FDA-approved lapatinib and gefitinib as well as a novel dual tyrosine kinase inhibitor (TKI) sapitinib, showed greater therapeutic efficacies. However, how 3D chromatin landscape responds to the inhibition of EGFR/HER2 pathway remains to be elucidated.

A novel progress of drug delivery system for organelle targeting in tumour cells.

At present, malignant tumours have become one of the most serious diseases that endanger human health. According to a survey on causes of death in Chinese population in early 1990s, the malignant tumours were the second leading cause of death. In the treatment of tumours, the ideal situation is that drugs should target and accumulate at tumour sites and destroy tumour cells specifically, without affecting normal cells and stem cells with regenerative capacity.

"Sushi roll" technique for precise total tongue functional reconstruction using a pre-sutured femoral anterolateral myocutaneous flap.

Objectives: Reconstruction of the total tongue after cancer resection remains one of the challenges in head and neck surgery. Inadequate reconstruction after subtotal or total glossectomy defects leads to poor quality of life. The aim of this study was to explore an economical, practical and effective flap design for functional tongue reconstruction.

HOXC10 promotes migration and invasion via the WNT-EMT signaling pathway in oral squamous cell carcinoma.

As a master regulator of embryonic morphogenesis, homeodomain-containing gene 10 (HOXC10) has been found to promote progression of human cancers and indicate poor survival outcome. Therefore, we concentrate on elucidating the role of HOXC10 in progression of oral squamous cell carcinoma (OSCC). In our study, the expression of HOXC10 was significantly increased in human OSCC samples and was significantly correlated with TNM stage and lymph node metastasis.

Long Non-Coding RNA Expression Profile Associated with Malignant Progression of Oral Submucous Fibrosis.

Oral submucous fibrosis (OSF) as one of the premalignant disorders endures a series of histopathological stages to invasive oral squamous cell carcinoma (OSCC) eventually. However, the role of long non-coding RNA (lncRNA) expression in OSF malignant progression still remains poorly understood. Through RNA-sequencing normal mucous, OSF and OSCC tissues, we found 687 lncRNA transcripts significantly and differentially expressed during OSF progression, including 231 upregulated lncRNAs and 456 downregulated lncRNAs, indicating that lncRNAs are involved in the regulation of different stages of OSF development.

Inhibition of ROS/NUPR1-dependent autophagy antagonises repeated cadmium exposure -induced oral squamous cell carcinoma cell migration and invasion.

Cadmium (Cd), an established carcinogen, is a risk factor for oral squamous cell carcinoma (OSCC). Macroautophagy/autophagy is proposed to play a pivotal role in Cd-mediated carcinogenic activity. However, the mechanisms underlying Cd-induced autophagy are poorly understood.

Biomarkers: paving stones on the road towards the personalized precision medicine for oral squamous cell carcinoma.

Traditional therapeutics have encountered a bottleneck caused by diagnosis delay and subjective and unreliable assessment. Biomarkers can overcome this bottleneck and guide us toward personalized precision medicine for oral squamous cell carcinoma. To achieve this, it is important to efficiently and accurately screen out specific biomarkers from among the huge number of molecules.

Inhibiting MT2-TFE3-dependent autophagy enhances melatonin-induced apoptosis in tongue squamous cell carcinoma.

Autophagy modulation is a potential therapeutic strategy for tongue squamous cell carcinoma (TSCC). Melatonin possesses significant anticarcinogenic activity. However, whether melatonin induces autophagy and its roles in cell death in TSCC are unclear.

Inhibiting ROS-NF-κB-dependent autophagy enhanced brazilin-induced apoptosis in head and neck squamous cell carcinoma.

Autophagy modulation has been considered a potential therapeutic strategy for head and neck squamous cell carcinoma (HNSCC). A previous study confirmed that brazilin might possess significant anti-carcinogenic activity. However, whether brazilin induces autophagy and its roles in cell death in HNSCC are still unclear.