Biofilm is a natural form of bacterial growth ubiquitously in environmental niches. The biofilm formation results in increased resistance to negative environmental influences including resistance to antibiotics and antimicrobial agents. Quorum sensing (QS) is cell-to-cell communication mechanism, which plays an important role in biofilm development and balances the environment when the bacteria density becomes high. Due to the prominent points of biofilms implicated in infectious disease and the spread of multi-drug resistance, it is urgent to discover new antibacterial agents that can regulate biofilm formation and development. Accumulated evidences demonstrated that natural products from plants had antimicrobial and chemo-preventive properties in modulation of biofilm formation in the last two decades. This review will summarize recent studies on the discovery of natural anti-biofilm agents from plants with clear-cut mechanisms or identified molecular addresses, as well as some herbs with unknown mechanisms or unidentified bioactive ingredients. We also focus on the progression of techniques on the extraction and identification of natural anti-biofilm substances. Besides, anti-biofilm therapeutics undergoing clinical trials are discussed. These newly discovered natural anti-biofilm agents are promising candidates which could provide novel strategies for biofilm-associated infections.

Background: Solid tumor hypoxic conditions prevent the generation of reactive oxygen species (ROS) and the formation of DNA double-strand breaks (DSBs) induced by ionizing radiation, which ultimately contributes to radiotherapy (RT) resistance. Recently, there have been significant technical advances in nanomedicine to reduce hypoxia by facilitating in situ O₂ production, which in turn serves as a “radiosensitizer” to increase the sensitivity of tumor cells to ionizing radiation. However, off-target damage to the tumor-surrounding healthy tissue by high-energy radiation is often unavoidable, and tumor cells that are further away from the focal point of ionizing radiation may avoid damage. Therefore, there is an urgent need to develop an intelligent targeted nanoplatform to enable precise enhanced RT-induced DNA damage and combined therapy. Results: Human epidermal growth factor receptor 2 (Her2)-specific dimeric affibody (Z_Her2) mediated cisplatin-loaded mesoporous polydopamine/MnO₂/polydopamine nanoparticles (Pt@mPDA/MnO₂/PDA-Z_Her2 NPs) for MRI and enhanced chemo-radiotherapy of Her2-positive ovarian tumors is reported. These NPs are biodegradable under a simulated tumor microenvironment, resulting in accelerated cisplatin release, as well as localized production of O₂. Z_Her2, produced using the E. coli expression system, endowed NPs with Her2-dependent binding ability in Her2-positive SKOV-3 cells. An in vivo MRI revealed obvious T₁ contrast enhancement at the tumor site. Moreover, these NPs achieved efficient tumor homing and penetration via the efficient internalization and penetrability of Z_Her2. These NPs exhibited excellent inhibition of tumor growth with X-ray irradiation. An immunofluorescence assay showed that these NPs significantly reduced the expression of HIF-1α and improved ROS levels, resulting in radiosensitization. Conclusions: The nanocarriers described in the present study integrated Her2 targeting, diagnosis and RT sensitization into a single platform, thus providing a novel approach for translational tumor theranostics. Graphic

Cluster of differentiation 44 (CD44) as a transmembrane glycoprotein is found to be expressed in non‑small cell lung cancer (NSCLC), is significantly associated with NSLC progression, metastasis and drug resistance. This study aimed to explore whether CD44 inhibition improves the sensitivity of epidermal growth factor receptor (EGFR) wild‑type NSCLC cells to cisplatin and how it affects wild‑type EGFR in NSCLC cells. Small interfering RNA was used to knockdown CD44 expression in EGFR wild‑type NSCLC cell line H460. Results suggested that CD44 downregulation reduced cell growth, promoted G0/G1 cell cycle arrest and induced cell apoptosis in H460 cells and these effects were evidently enhanced when in combination with cisplatin. Deactivation of EGFR signaling pathway including EGFR phosphorylation and its downstream molecules, targets ERK, AKT1 and SRC which were also observed in CD44‑silenced H460 cells with or without EGF stimulation. Furthermore, the CD44 expression level was positively correlated with wild‑type EGFR level in human lung adenocarcinoma tissues and CD44 inhibition significantly accelerated the degradation of EGFR, indicating that enhanced sensitivity of H460 cells to cisplatin by downregulation of CD44 might be due to EGFR degradation. This study demonstrated that suppression of CD44 deactivated EGFR signals in NSCLC cells with wild‑type EGFR, thereby contributing to the inhibition of cell proliferation and the reinforcement of cisplatin sensitivity. It is suggested that downregulation of CD44 could be a novel potential therapeutic strategy for the treatment of EGFR wild‑type NSCLC.

Most patients with hepatocellular carcinoma (HCC) develop resistance to immune checkpoint blockade (ICB) or STING agonists despite their immune-stimulating activities. Here, we identify increased intratumoral B-cell infiltration as a mediator of acquired resistance. In HCC models with liver fibrosis in male mice, anti-PD-1 ICB or the STING agonist BMS-986301 increase intratumoral B-cell infiltration, circulating IL-10, and TIM-1⁺ B-cells, promoting tertiary lymphoid structure formation. B-cell depletion combined with ICB or STING agonism improves survival, and STING agonism inhibits distant metastasis. In addition, co-targeting STING and TIM-1 enhances B-cell differentiation and antigen presentation, reduces intratumoral TIM-1⁺ B-cells, and increases CD86 and MHC class II expression, thereby augmenting CD8⁺ T-cell-mediated anti-tumor immunity. These findings reveal that B-cells contribute to ICB and STING therapy resistance in HCC, and that B-cell depletion or TIM-1 blockade can overcome acquired resistance to these immunotherapies.

This study delineated the elucidate molecular changes and their post-translational modifications (PTMs) in heterogenetic colorectal cancer (CRC) for a deeper understanding of the CRC pathophysiology and identifying potential therapeutic targets. In this retrospective study, the profiles of 13 hot spot gene mutations were analyzed and the microsatellite instability (MSI) status was determined.Employing the Circulating Single-Molecule Amplification and Resequencing Technology (cSMART) assay, the clinical-pathological features of CRC were characterized in 249 Chinese patients. PTMs were quantified online.Among the patients with CRC, the mutation frequencies of KRAS, NRAS, BRAF, PIK3CA, TP53, and APC genes were 47.8%, 3.6%, 4.8%, 13.7%, 55.8%, and 36.9%, respectively. The proportion of MSI-high (MSI-H) was 7.8%.Subsequent multiple logistic regression analysis showed significant associations including a link between lung metastasis and KRAS mutation, between liver metastasis and lymph node metastasis, between MSI-H and early-onset CRC (EOCRC) and KRAS mutation, between right-sided colon cancer and peritoneal metastasis, and between PIK3CA mutation and PTEN mutation. Patients with KRAS mutation presented with MSI-H, lung metastasis, and PIK3CA mutation. MSI-H, BRAF mutation, and PTEN mutation were more frequent in EOCRC. Phosphorylation and ubiquitylation were found in KRAS, BRAF, PTEN, and SMAD4; SUMOylation and ubiquitylation were observed in HRAS and NRAS; while phosphorylation was obvious in APC, P53, and MLH1. Notably, Phosphorylation and ubiquitylation were the two most common PTMs. The biological characteristics of CRC in Chinese patients have some unique clinical features, which can be explained by the genetic mutation profile, correlations among gene mutations and clinical characteristics. These distinctions set the Chinese patient population apart from their Western counterparts.