ALKBH1: emerging biomarker and therapeutic target for cancer treatment.

As neoplastic cells proliferate, disseminate, and infiltrate, they undergo substantial alterations in their epigenetic configuration. Among the pivotal enzymes implicated in this phenomenon is the AlkB family of demethylases, notably AlkB homolog 1 (ALKBH1), which demonstrates conspicuous upregulation across various malignancies. The heightened expression of ALKBH1 renders it a compelling candidate for the development of multifaceted anticancer modalities.

RN486, a Bruton's Tyrosine Kinase inhibitor, antagonizes multidrug resistance in ABCG2-overexpressing cancer cells.

Background And Objectives: Overcoming ATP-binding cassette subfamily G member 2 (ABCG2)-mediated multidrug resistance (MDR) has attracted the attention of scientists because one of the critical factors resulting in MDR in cancer is the overexpression of ABCG2. RN486, a Bruton's Tyrosine Kinase (BTK) inhibitor, was discovered to potentially reverse ABCB1-mediated MDR. However, there is still uncertainty about whether RN486 has a reversal off-target impact on ABCG2-mediated MDR.

Combating antimicrobial resistance: the silent war.

Once hailed as miraculous solutions, antibiotics no longer hold that status. The excessive use of antibiotics across human healthcare, agriculture, and animal husbandry has given rise to a broad array of multidrug-resistant (MDR) pathogens, posing formidable treatment challenges. Antimicrobial resistance (AMR) has evolved into a pressing global health crisis, linked to elevated mortality rates in the modern medical era.

Fully biobased hydrogel based on chitosan and tannic acid coated cotton fabric for underwater superoleophobicity and efficient oil/water separation.

Underwater superoleophobic (UWSO) materials have garnered significant attention in separating oil/water mixtures. But, the majority of these materials are made from non-degradable and non-renewable raw materials, polluting the environment and wasting scarce resources while using them. Against this backdrop, this study aimed to fabricate an environmental-friendly UWSO textile using biobased materials.

Fabrication of well-dispersed cellulose nanocrystal reinforced biobased epoxy composites using reversibility of covalent adaptable network.

Cellulose nanocrystal (CNC) shows great potential in reinforced composites but it is difficult to disperse in epoxy thermosets due to its poor dispersity in epoxy monomers. Herein, we reported a novel approach to disperse CNC in epoxidized soybean oil (ESO)-derived epoxy thermosets uniformly by using the reversibility of dynamic imine-containing ESO-derived covalent adaptable network (CAN). The crosslinked CAN was deconstructed by an exchange reaction with ethylenediamine (EDA) in dimethyl formamide (DMF), leading to a solution of deconstructed CAN with plenty of hydroxyl and amino groups, which could form strong hydrogen bonds with hydroxyl groups of CNC and thus facilitated and stabilized dispersion of CNC in the deconstructed CAN solution.

A multi-functional nano-system combining PI3K-110α/β inhibitor overcomes P-glycoprotein mediated MDR and improves anti-cancer efficiency.

P-glycoprotein (P-gp/ABCB1)-mediated multidrug resistance (MDR) in cancers severely limit chemotherapeutic efficacy. We recently reported that phosphatidylinositol-3-kinase (PI3K) 110α and 110β subunits can be novel targets for reversal of P-gp mediated MDR in cancers, and BAY-1082439 as an inhibitor specific for PI3K 110α and 110β subunits could reverse P-gp-mediated MDR by downregulating P-gp expression in cancer cells. However, BAY-1082439 has very low solubility, short half-life and high in-vivo clearance rate.

Fully biobased poly(lactic acid)/lignin composites compatibilized by epoxidized natural rubber.

Biobased poly(lactic acid)/lignin (PLA/lignin) composites are limited by poor mechanical properties resulted from poor compatibility and low interfacial adhesion. Herein, we reported a novel approach to improve compatibility and interfacial adhesion of PLA/lignin composites via reactive compatibilization with epoxidized natural rubber (ENR) as a compatibilizer. Interfacial tension calculation indicated that lignin tended to act as interfacial phase between PLA and ENR, but morphology analysis demonstrated lignin was wrapped with a layer of ENR and dispersed in PLA matrix, which was attributed to the interfacial reaction of ENR with both PLA and lignin.

Nivolumab and relatlimab for the treatment of melanoma.

Melanoma is a highly lethal type of skin cancer. Although an early diagnosis, in combination with surgery for nonmetastatic melanomas, significantly increases the probability of survival, there are no efficacious treatments for metastatic melanoma. Nivolumab and relatlimab are monoclonal antibodies that selectively interact with and block the proteins programmed cell death protein 1 (PD-1) and lymphocyte activation protein 3 (LAG-3), respectively, and thus, their activation by their cognate ligands.

The Roles of Exosomal microRNAs in Diffuse Large B-Cell Lymphoma: Diagnosis, Prognosis, Clinical Application, and Biomolecular Mechanisms.

Background: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous neoplasm and is characterized as the most common subtype of non-Hodgkin lymphoma (NHL). Despite 60-70% of all patients being cured with R-CHOP therapeutic regimen (Cyclophosphamide, doxorubicin, vincristine, and prednisone, combined with rituximab), remaining patients display aggressive disease. Therefore, there is an urgent need to develop novel diagnostic, prognostic, and predictive biomarkers.

Ribociclib Inhibits P-gp-Mediated Multidrug Resistance in Human Epidermoid Carcinoma Cells.

The efficacy of cancer chemotherapy can be attenuated or abrogated by multidrug resistance (MDR) in cancer cells. In this study, we determined the effect of the CDK4/6 inhibitor, ribociclib (or LEE011), on P-glycoprotein (P-gp)-mediated MDR in the human epidermoid carcinoma MDR cell line, KB-C2, which is widely used for studying P-gp-mediated MDR in cancers. The incubation of KB-C2 cells with ribociclib (3-9 µM) increased the efficacy of colchicine, a substrate for P-gp.

Mitochondrial oxidative phosphorylation is dispensable for survival of CD34 chronic myeloid leukemia stem and progenitor cells.

Chronic myeloid leukemia (CML) are initiated and sustained by self-renewing malignant CD34 stem cells. Extensive efforts have been made to reveal the metabolic signature of the leukemia stem/progenitor cells in genomic, transcriptomic, and metabolomic studies. However, very little proteomic investigation has been conducted and the mechanism regarding at what level the metabolic program was rewired remains poorly understood.

Biobased mussel-inspired underwater superoleophobic chitosan derived complex hydrogel coated cotton fabric for oil/water separation.

Superhydrophilic and underwater superoleophobic materials exhibit excellent oil/water separation performance but are usually fabricated from nonrenewable and nondegradable feedstocks and thus would cause secondary pollution after use. Herein, we report a fully biobased and mussel-inspired underwater superoleophobic hydrogel coated cotton fabric (CF) prepared by surface coating and subsequent oxidation polymerization of chitosan & dopamine mixtures. The obtained chitosan & polydopamine hydrogel coated CF (CS&PDA/CF) showed superhydrophilicity and underwater superoleophobicity, due to the formed rough surface structure with hydrophilic complex hydrogel.

STAT6 Blockade Abrogates -Induced Eosinophilic Chronic Rhinosinusitis and Asthma, A Model of Unified Airway Disease.

Unified airway disease, including concurrent asthma and chronic rhinosinusitis (CRS), is a common, but poorly understood disorder with no curative treatment options. To establish a murine model of chronic unified eosinophilic airway inflammation, mice were challenged with , and sinonasal mucosa and lung tissue were evaluated by immunohistochemistry, flow cytometry, and gene expression. Inhalation of conidia resulted in a Th2-biased lung and sinus inflammation that typifies allergic asthma and CRS.

Research progress in overcoming ibrutinib drug resistance.

Ibrutinib, an oral small-molecule targeted drug, has been the first Bruton tyrosine kinase (BTK) inhibitor in the world to be approved for the market. It works by regulating cell proliferation, apoptosis and migration, and has been proven to exhibit high efficacy and good safety in the treatment of B-cell lymphomas, including chronic lymphocytic leukemia or small lymphocytic lymphoma and mantle cell lymphoma. However, some patients inevitably have drug resistance and disease recurrence, resulting in a poor prognosis.

Extracellular Vesicles in Acute Leukemia: A Mesmerizing Journey With a Focus on Transferred microRNAs.

Despite their small size, the membrane-bound particles named extracellular vesicles (EVs) seem to play an enormous role in the pathogenesis of acute leukemia. From oncogenic hematopoietic stem cells (HSCs) to become leukemic cells to alter the architecture of bone marrow (BM) microenvironment, EVs are critical components of leukemia development. As a carrier of essential molecules, especially a group of small non-coding RNAs known as miRNA, recently, EVs have attracted tremendous attention as a prognostic factor.

ATP-binding cassette (ABC) transporters in cancer: A review of recent updates.

The ATP-binding cassette (ABC) transporter superfamily is one of the largest membrane protein families existing in wide spectrum of organisms from prokaryotes to human. ABC transporters are also known as efflux pumps because they mediate the cross-membrane transportation of various endo- and xenobiotic molecules energized by ATP hydrolysis. Therefore, ABC transporters have been considered closely to multidrug resistance (MDR) in cancer, where the efflux of structurally distinct chemotherapeutic drugs causes reduced itherapeutic efficacy.

CMP25, a synthetic new agent, targets multidrug resistance-associated protein 7 (MRP7/ABCC10).

Multidrug resistance-associated protein 7 (MRP7) is an important member of ABC transporter superfamily and has been revealed to mediate the cross-membrane translocation of a wide range of chemotherapeutic agents including taxanes, epothilones, Vinca alkaloids, Anthracyclines and Epipodophyllotoxins.In our previous study, a 1,2,3-triazole-pyrimidine hybridCMP25was synthesized and found able to efficiently reverse multidrug resistance (MDR) mediated by P-glycoprotein. In this study, we evaluated the efficacy of compound CMP25in reversing MDR mediated by MRP7in vitro.

Bruton's Tyrosine Kinase (BTK) Inhibitor RN486 Overcomes ABCB1-Mediated Multidrug Resistance in Cancer Cells.

Overexpression of ATP-binding cassette subfamily B member 1 (ABCB1) remains one of the most vital factors leading to multidrug resistance (MDR). It is important to enhance the effect and bioavailability of chemotherapeutic drugs that are substrates of ABCB1 transporter in ABCB1-overexpression cancer cells and reverse ABCB1-mediated MDR. Previous, we uncovered that the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib is a potent reversal agent to overcomes paclitaxel resistance in ABCB1-overexpressing cells and tumors.

Methyl-Cantharidimide (MCA) Has Anticancer Efficacy in ABCB1- and ABCG2-Overexpressing and Cisplatin Resistant Cancer Cells.

In this study, we investigated the efficacy of methyl-cantharidimide (MCA), a cantharidin (CTD) analog, as an anticancer drug, in cancer cells overexpressing either ABCB1 or ABCG2 transporters and in cisplatin-resistant cancer cells. The results indicated that: (i) MCA was efficacious in the ABCB1-overexpressing cell line, KB-C2, and the ABCB1-gene-transfected cell line, HEK293/ABCB1 (IC50 from 6.37 to 8.

Mussel-inspired chitosan modified superhydrophilic and underwater superoleophobic cotton fabric for efficient oil/water separation.

Superhydrophilic and underwater superoleophobic textiles exhibit excellent oil/water separation performance but are limited by the poor stability and environmental incompatibility. Inspired by strong adhesion of marine mussels, we designed and fabricated a stable and eco-friendly superhydrophilic and underwater superoleophobic cotton fabric (CF) from all renewable resources through in-situ surface deposition of polydopamine (PDA) particles followed by adsorption of hydrophilic chitosan via dip coating at room temperature. The as-prepared superhydrophilic and underwater superoleophobic CF exhibited outstanding oil/water separation performance with separation efficiency and water flux higher than 99 % and 15,000 L m h, respectively.

In response to complement anaphylatoxin peptides C3a and C5a, human vascular endothelial cells migrate and mediate the activation of B-cells and polarization of T-cells.

The vascular endothelium has been discovered in the past several years to be important in shaping the cellular immune response. During the immune response the vascular endothelium is constantly perturbed by biologically potent molecules, including the complement activation peptides, C3a and C5a. Despite the importance of C3a and C5a in inflammation and immunity, their role in modulating lymphocyte function via activation of vascular endothelial cells is unknown.

Robust and nanoparticle-free superhydrophobic cotton fabric fabricated from all biological resources for oil/water separation.

Traditional superhydrophobic cotton fabrics (SCFs) for oil/water separation were usually fabricated by surface coating with inorganic nanoparticles combined with nonrenewable and nonbiodegradable or even toxic fossil-based chemicals, which would lead to secondary environmental pollution after their lifetime. In this study, we report robust, nanoparticle-free, fluorine-free SFC, which was prepared by acid etching followed by surface coating with epoxidized soybean oil resin (CESO) and subsequent modification with stearic acid (STA). No toxic compound and no nanoparticle were included within the SCF and all the raw materials including cotton fabric, CESO and STA are biodegradable and derived from biological resources.

Cellulose nanocrystal coated cotton fabric with superhydrophobicity for efficient oil/water separation.

Cellulose nanocrystal (CNC) with renewability, biodegradability, and nanoscale size was used as the rough structure component instead of inorganic nanoparticles to fabricate renewable and degradable superhydrophobic cotton fabric via a dip-coating method with cured epoxidized oil resin (CESO) as the binder. The superhydrophobic cotton fabric could selectively absorb oil from oily water and could separate various oil/water mixture very efficiently with separation efficiency higher than 98%. The superhydrophobic cotton fabric showed excellent stability, making it reusable for several times without lowering separation efficiency.

Morphology, crystallization and rheological behavior in poly(butylene succinate)/cellulose nanocrystal nanocomposites fabricated by solution coagulation.

Nanocomposites consisting of poly(butylene succinate) (PBS) and cellulose nanocrystals (CNC) were fabricated by solution coagulation method. Morphology analysis indicated that CNC dispersed well in PBS matrix and rheological analysis suggested that PBS and CNC showed strong interactions. Thermal analysis indicated that the nanocomposites showed slightly increased glass transition temperature, significantly enhanced crystallization temperature and different melting behavior, compared to neat PBS.