HOXB8 mediates resistance to cetuximab in colorectal cancer cells through activation of the STAT3 pathway.

Homeobox B8 (HOXB8) belongs to the HOX family and was essential to the development of colorectal carcinoma. Among the prevalent monoclonal antibodies for treating RAS/BRAF wild-type metastatic colorectal cancer (mCRC) patients, cetuximab stands out, but resistance to cetuximab frequently arises in targeted treatments. Currently, the role of HOXB8 in cetuximab-resistant mCRC remains unclear.

Comparative in Silico study of apigenin and its dimeric forms on PIM1 kinase in glioblastoma multiform.

This study aimed to investigate and compare the binding affinity of apigenin and its dimeric flavonoid forms to PIM1 kinase in glioblastoma multiforme (GBM), an aggressive and lethal brain cancer. Apigenin is a natural herbal product that has demonstrated anti-cancer effects in numerous studies, both in vitro and in vivo, on various cancers. Our in silico analysis showed that PIM1 expression was significantly higher in GBM tumor tissue compared to normal brain tissue, and high PIM1 expression correlated with worse survival rates in patients with GBM.

Zein-PEG nanoparticles modified with hyaluronic acid for paclitaxel delivery in SKOV3 ovarian cancer cells.

Ovarian cancer is a leading gynecological cancer globally. This study aimed to develop hyaluronic acid-modified polyethylene glycol conjugated zein nanoparticles (zein-PEG/HA NPs) to enhance paclitaxel (PTX) cytotoxicity in SKOV3 ovarian cancer cells. Zein-PEG, with its amphiphilic nature, self-assembled into micelles to encapsulate the hydrophobic PTX, while the PEG shell retained micelle stability and hemolytic resistance.

Enzyme-Sialylation-Controlled Chemical Sulfation of Glycan Epitopes for Decoding the Binding of Siglec Ligands.

Widely distributed in nature, sulfated glycan epitopes play important roles in diverse pathophysiological processes. However, due to their structural complexity, the preparation of glycan epitopes with structurally defined sulfation patterns is challenging, which significantly hampers the detailed elucidation of their biological functions at the molecular level. Here, we introduce a strategy for site-specific chemical sulfation of glycan epitopes, leveraging enzymatic sialylation and desialylation processes to precisely control the regio-specificity of sulfation of disaccharide or trisaccharide glycan backbones.

Photoelectric HS Sensing Based on Electrospun Hollow CuO-SnO Nanotubes at Room Temperature.

Pure tin oxide (SnO) as a typical conductometric hydrogen sulfide (HS) gas-sensing material always suffers from limited sensitivity, elevated operation temperature, and poor selectivity. To overcome these hindrances, in this work, hollow CuO-SnO nanotubes were successfully electrospun for room-temperature (25 °C) trace HS detection under blue light activation. Among all SnO-based candidates, a pure SnO sensor showed no signal, even toward 10 ppm, while the 1% CuO-SnO sensor achieved a limit of detection (LoD) value of 2.

Near-Infrared Activatable Copper Nanoplatforms Synergize with the 5-Azacytidine Prodrug to Potentiate Cuproptosis.

Cuproptosis, a newly discovered cell death modality, is gaining recognition for its crucial role in antitumor therapy. Here, we demonstrated that Ferredoxin 1 (FDX1), a key gene involved in cuproptosis, is negatively correlated with malignancy and T-cell exhaustion in head and neck squamous cell carcinoma (HNSCC). Based on these findings, we developed near-infrared (NIR) light-controlled nanoparticles (NPs), CuD@PM, which can selectively deliver copper to HNSCC cells and induce cuproptosis in the presence of microneedles loaded with triacetylated azacitidine (TAc-AzaC) and 808 nm laser irradiation.

The hallmarks of tissue-agnostic therapies and strategies for early anticancer drug discovery.

Recently, precision medicine has enabled biomarker-driven treatment to be administered in a pan-tumor setting, so-called tissue-agnostic therapy. This represents a paradigm shift in cancer care from conventional cancer type-specific to biomarker-centric care, where patients are selected for this type of therapy based on molecular aberrations that occur across cancer types, regardless of tumor site or histology. This approach is particularly important because it offers new treatment options for patients with rare cancers or for whom there are no adequate treatments.

Mapping new psychoactive substances: Leveraging GIS technology for advanced global surveillance and policy support.

The escalating challenge of New Psychoactive Substances (NPS) necessitates enhanced global monitoring and analysis capabilities. This study introduces an advanced interactive visualization tool that employs Geographic Information System (GIS) technologies to improve the functionality of the UNODC's Early Warning Advisory. The tool enables dynamic observation and analysis of NPS's geographical and temporal distribution, thereby facilitating a comprehensive understanding of their public health impacts.

Cabozantinib-encapsulated and maytansine-conjugated high-density lipoprotein for immunotherapy in colorectal cancer.

Advanced colorectal cancer (CRC) responds poorly to current adjuvant therapies, partially due to its immunosuppressive intestinal microenvironment. We found that myeloid-derived suppressor cells (MDSCs) were enriched in orthotopic tumors due to treatment-induced succinate release, which activated tuft cells and upregulated interleukin 25 (IL-25) and interleukin 13 (IL-13). We engineered a cabozantinib (Cabo)-encapsulated and maytansine (DM1)-conjugated synthetic high-density lipoprotein (CD-sHDL) to modulate the tumor microenvironment.

Synthesis of Thiohydantoin Scaffolds on DNA for Focused DNA-Encoded Library Construction.

Thiohydantoin represents a significant class of biologically active privileged heterocyclic scaffolds. Herein, we present a convenient and robust DNA-compatible method for constructing a thiohydantoin-focused DNA-encoded library. This reaction can be applied to a wide variety of isothiocyanate partners, arylamine feedstocks, and diverse α-amine acid derivatives, exhibiting excellent conversions, high functional group tolerance, and preservation of DNA tag integrity.

Discovery of selective LATS inhibitors scaffold hopping: enhancing drug-likeness and kinase selectivity for potential applications in regenerative medicine.

Due to its essential roles in cell proliferation and apoptosis, the precise regulation of the Hippo pathway through LATS presents a viable biological target for developing new drugs for cancer and regenerative diseases. However, currently available probes for selective and highly drug-like inhibition of LATS require further improvement in terms of both activity, selectivity and drug-like properties. Through scaffold hopping aided by docking studies and AI-assisted prediction of metabolic stabilities, we successfully identified an advanced LATS inhibitor demonstrating potent kinase activity, exceptional selectivity against other kinases, and superior oral pharmacokinetic profiles.

An Approach for Highly Enantioselective Synthesis of -Disubstituted []Paracyclophanes.

Atroposelective synthesis of -disubstituted []paracyclophanes is a difficult task in organic chemistry. We describe a facile approach for the synthesis of -disubstituted []paracyclophanes using Pd-catalyzed enantioselective C-H olefination and sequential reductive cleavage. A wide range of []paracyclophanes was obtained with excellent enantioselectivity.

Strategy for Construction of Homogeneous Glycoproteins in Mammalian Cells.

A general strategy that combines genetic code expansion with bio-orthogonal ligation techniques was developed and utilized to prepare homogeneously glycosylated receptors on the surface of mammalian cells. Using this approach, conjugates of the cell-surface oxytocin receptor (OTR) with oligosaccharides were efficiently generated in the cells. Cell studies revealed that glycans linked to the OTR are not essential for agonist-induced calcium flux and its internalization into cells via an OTR-mediated endocytosis.

The Effect of Monobenzone Cream on Oxidative Stress and Its Relationship With Serum Levels of IL-1β and IL-18 in Vitiligo Patients.

Background: Monobenzyl ether hydroquinone (MEBHQ) is a cream that promotes the spread and evenness of skin patches in vitiligo. Our aim was to investigate the oxidative and inflammatory effects of this cream on vitiligo patients consuming MEBHQ.

Methods: A case-control study was conducted with three groups of 30 people from the control group, vitiligo patients before and after treatment.

Zhumeria majdae essential oil attenuates TNBS-induced colitis in rats by regulating inflammatory and apoptotic pathways.

Background And Aim: Zhumeria majdae, a unique native plant of southern Iran, has been traditionally used to treat various health issues. Preclinical studies suggest its therapeutic potential for immunological and inflammatory disorders. This study investigates the effect of Z.

Confined copper depletion via a hydrogel platform for reversing dabrafenib/cetuximab resistance in BRAF-mutant colorectal cancer.

BRAF-mutant colorectal cancer (CRC) is resistant to most first-line therapeutics, including the BRAF inhibitor dabrafenib and epidermal growth factor receptor (EGFR) inhibitor cetuximab. Although copper depletion shows promise in reversing dabrafenib/cetuximab resistance in BRAF-mutant CRC, its application is limited by the potential for excessive copper depletion in non-tumor objects. In this study, we have developed a hydrogel platform for confined copper depletion in BRAF-mutant CRC cells, which effectively reverses dabrafenib/cetuximab resistance and enhancing therapeutic efficiency.

Exploring the Therapeutic Potential of BBB-Penetrating Phytochemicals With p38 MAPK Modulatory Activity in Addressing Oxidative Stress-Induced Neurodegenerative Disorders, With a Focus on Alzheimer's Disease.

Oxidative stress plays an important role in the occurrence of neurodegenerative diseases. Previous studies indicate a strong connection between oxidative stress, inappropriate activation of the p38 MAPK signaling pathway, and the pathogenesis of neurodegenerative diseases. Although antioxidant therapy is a valid strategy to alleviate these problems, the most important limitation of this approach is the ineffectiveness of drug administration due to the limited permeability of the BBB.

DNA-Encoded Noncanonical Substrate Library for Protease Profiling.

Profiling the substrate sequence preferences of proteases is important for understanding both biological functions as well as for designing protease inhibitors. Several methods are available for profiling the sequence specificity of proteases. However, there is currently no rapid and high-throughput method to profile specificity of proteases for noncanonical substrates.

Establishment and validation of a nomogram model containing a triglyceride-glucose index and neutrophil-to-high-density lipoprotein ratio for predicting major adverse cardiac events in patients with ST-segment elevation myocardial infarction.

Objective: To analyze the predictive value of the triglyceride-glucose (TyG) index and neutrophil-to-high-density lipoprotein ratio (NHR) for in-hospital major adverse cardiac events (MACE) after percutaneous coronary intervention (PCI) in patients with acute ST-segment elevation myocardial infarction (STEMI), and to establish an associated nomogram model.

Methods: In this retrospective study, we collected data from consecutive STEMI patients who underwent PCI from October 2019 to June 2023 at the Second People's Hospital of Hefei and the Second Affiliated Hospital of Anhui Medical University, as training and validation sets. Stepwise regression and multivariate logistic regression analysis were performed to screen independent risk factors, and a nomogram model was constructed and evaluated for its predictive efficacy.

Investigating the Effects of Simultaneous Administration of Melatonin and Atorvastatin against High Glucose-Induced Oxidative Stress and Apoptosis in Cultured Chondrocytes.

Objective: Osteoarthritis (OA) is a prevalent joint disorder categorized into phenotypic subtypes, including those associated with age, traumatic events, and metabolic syndrome. In the aging population, type 2 diabetes mellitus (T2DM) and osteoarthritis (OA) frequently coexist. This can result in higher rates of disability and a greater financial burden.