Cationic conjugated polymers with tunable hydrophobicity for efficient treatment of multidrug-resistant wound biofilm infections.

Biofilm-associated infections arising from antibiotic-resistant bacteria pose a critical challenge to global health. We report the generation of a library of cationic conjugated poly(phenylene ethynylene) (PPE) polymers featuring trimethylammonium terminated sidechains with tunable hydrophobicity. Screening of the library identified an amphiphilic polymer with a C hydrophobic spacer as the polymer with the highest antimicrobial efficacy against biofilms in the dark with excellent selectivity.

Controlled bioorthogonal catalyst self-assembly and activity using rationally designed polymer scaffolds.

Polymer-based nanocatalysts have been extensively utilized in advanced drug delivery due to their versatility and high reactivity. Incorporating bioorthogonal transition metal catalysts (TMCs) into polymers generates bioorthogonal nanocatalysts capable of producing therapeutic agents , minimizing off-target effects. The supramolecular interactions within the polymer matrix, including hydrophobic interactions and aromatic stacking, play a crucial role in catalytic properties.

All-Natural Gelatin-Based Nanoemulsion Loaded with TLR 7/8 Agonist for Efficient Modulation of Macrophage Polarization for Immunotherapy.

Macrophages are multifunctional immune cells essential for both innate and adaptive immune responses. Tumor-associated macrophages (TAMs) often adopt a tumor-promoting M2-like phenotype, aiding tumor progression and immune evasion. Reprogramming TAMs to a tumoricidal M1-like phenotype is an emerging target for cancer immunotherapy.

Engineered Bacteriophage-Polymer Nanoassemblies for Treatment of Wound Biofilm Infections.

The antibacterial efficacy and specificity of lytic bacteriophages (phages) make them promising therapeutics for treatment of multidrug-resistant bacterial infections. Restricted penetration of phages through the protective matrix of biofilms, however, may limit their efficacy against biofilm infections. Here, engineered polymers were used to generate noncovalent phage-polymer nanoassemblies (PPNs) that penetrate bacterial biofilms and kill resident bacteria.

Surface-Charge Tuned Polymeric Nanoemulsions for Carvacrol Delivery in Interkingdom Biofilms.

Biofilms, intricate microbial communities entrenched in extracellular polymeric substance (EPS) matrices, pose formidable challenges in infectious disease treatment, especially in the context of interkingdom biofilms prevalent in the oral environment. This study investigates the potential of carvacrol-loaded biodegradable nanoemulsions (NEs) with systematically varied surface charges─cationic guanidinium (GMT-NE) and anionic carboxylate (CMT-NE). Zeta potentials of +25 mV (GMT-NE) and -33 mV (CMT-NE) underscore successful nanoemulsion fabrication (∼250 nm).

Nature-Derived Gelatin-Based Antifungal Nanotherapeutics for combatting Biofilms.

Infections caused by fungi are emerging global health challenges that are exacerbated by the formation of fungal biofilms. Further challenges arise from environmental contamination with antifungal agents, which promotes environmental acquisition of antifungal resistance. We report the generation of an efficient, sustainable, all-natural antifungal nanotherapeutic based on the integration of an antimicrobial natural essential oil into a gelatin-based nanoemulsion platform.

Polarization of macrophages to an anti-cancer phenotype through uncaging of a TLR 7/8 agonist using bioorthogonal nanozymes.

Macrophages are plastic cells of the immune system that can be broadly classified as having pro-inflammatory (M1-like) or anti-inflammatory (M2-like) phenotypes. M2-like macrophages are often associated with cancers and can promote cancer growth and create an immune-suppressive tumor microenvironment. Repolarizing macrophages from M2-like to M1-like phenotype provides a crucial strategy for anticancer immunotherapy.

Discovery of dual kinase inhibitors targeting VEGFR2 and FAK: structure-based pharmacophore modeling, virtual screening, and molecular docking studies.

VEGFR2 and FAK signaling pathways are interconnected and have synergistic effects on tumor angiogenesis, growth, and metastasis. Thus, instead of the conventional targeting of each of these proteins individually with a specific inhibitor, the present work aimed to discover novel dual inhibitors targeting both VEGFR2 and FAK exploiting their association. To this end, receptor-based pharmacophore modeling technique was opted to generate 3D pharmacophore models for VEGFR2 and FAK type II kinase inhibitors.

Antimicrobial-loaded biodegradable nanoemulsions for efficient clearance of intracellular pathogens in bacterial peritonitis.

Intracellular pathogenic bacteria use immune cells as hosts for bacterial replication and reinfection, leading to challenging systemic infections including peritonitis. The spread of multidrug-resistant (MDR) bacteria and the added barrier presented by host cell internalization limit the efficacy of standard antibiotic therapies for treating intracellular infections. We present a non-antibiotic strategy to treat intracellular infections.

Antimicrobial polymer-siRNA polyplexes as a dual-mode platform for the treatment of wound biofilm infections.

Treatment of wound biofilm infections faces challenges from both pathogens and uncontrolled host immune response. Treating both issues through a single vector would provide enhanced wound healing. Here, we report the use of a potent cationic antimicrobial polymer to generate siRNA polyplexes for dual-mode treatment of wound biofilms These polyplexes act both as an antibiofilm agent and a delivery vehicle for siRNA for the knockdown of biofilm-associated pro-inflammatory MMP9 in host macrophages.

Antimicrobial polymer-loaded hydrogels for the topical treatment of multidrug-resistant wound biofilm infections.

Integration of antimicrobial polymeric nanoparticles into hydrogel materials presents a promising strategy to address multidrug-resistant biofilm infections. Here we report an injectable hydrogel loaded with engineered cationic antimicrobial polymeric nanoparticles (PNPs) for the effective topical treatment of severe wound biofilm infections. The PNPs demonstrated biofilm penetration and disruption, resulting in the eradication of resistant and persister cells that reside within the biofilm.

Biodegradable nanoemulsion-based bioorthogonal nanocatalysts for intracellular generation of anticancer therapeutics.

Bioorthogonal catalysis mediated by transition metal catalysts (TMCs) provides controlled activation of prodrugs through chemical reactions that do not interfere with cellular bioprocesses. The direct use of 'naked' TMCs in biological environments can have issues of solubility, deactivation, and toxicity. Here, we demonstrate the design and application of a biodegradable nanoemulsion-based scaffold stabilized by a cationic polymer that encapsulates a palladium-based TMC, generating bioorthogonal nanocatalyst "polyzymes".

Synergistic Treatment of Multidrug-Resistant Bacterial Biofilms Using Silver Nanoclusters Incorporated into Biodegradable Nanoemulsions.

Multidrug resistance (MDR) in bacteria is a critical global health challenge that is exacerbated by the ability of bacteria to form biofilms. We report a combination therapy for biofilm infections that integrates silver nanoclusters (AgNCs) into polymeric biodegradable nanoemulsions (BNEs) incorporating eugenol. These Ag-BNEs demonstrated synergistic antimicrobial activity between the AgNCs and the BNEs.

Suppression of neuronal apoptosis and glial activation with modulation of Nrf2/HO-1 and NF-kB signaling by curcumin in streptozotocin-induced diabetic spinal cord central neuropathy.

Introduction: Diabetes is a global disease, commonly complicated by neuropathy. The spinal cord reacts to diabetes by neuronal apoptosis, microglial activation, and astrocytosis, with a disturbance in neuronal and glial Nuclear factor erythroid 2-related factor/Heme oxygenase-1 (Nrf2/HO-1) and Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) signaling. Curcumin, a bioactive natural substance, showed neuroprotective role in many diseases.

All-natural gelatin-based bioorthogonal catalysts for efficient eradication of bacterial biofilms.

Bioorthogonal catalysis mediated by transition metal catalysts (TMCs) presents a versatile tool for generation of diagnostic and therapeutic agents. The use of 'naked' TMCs in complex media faces numerous obstacles arising from catalyst deactivation and poor water solubility. The integration of TMCs into engineered inorganic scaffolds provides 'nanozymes' with enhanced water solubility and stability, offering potential applications in biomedicine.

Effect of Zr and Ti Addition and Aging Treatment on the Microstructure and Tensile Properties of Al-2%Cu-Based Alloys.

The present work investigated the effect of aging treatment on the microstructure and tensile properties of an Al-2%Cu base alloy containing various additions of Zr and other alloying elements. Aging was carried out at temperatures of 180-300 °C for different aging times at each temperature. The tensile properties indicated that Zr additions improved the strength of the base alloy, especially at high Zr levels at 180 °C.

A Polymer-Based Multichannel Sensor for Rapid Cell-Based Screening of Antibiotic Mechanisms and Resistance Development.

Antibiotic resistance presents a critical threat to public health, necessitating the rapid development of novel antibiotics and an appropriate choice of therapeutics to combat refractory bacterial infections. Here, we report a high-throughput polymer-based sensor platform that rapidly (30 min) profiles mechanisms of antibiotic activity. The sensor array features three fluorophore-conjugated polymers that can detect subtle antibiotic-induced phenotypic changes on bacterial surfaces, generating distinct mechanism-based fluorescence patterns.

Dual antimicrobial-loaded biodegradable nanoemulsions for synergistic treatment of wound biofilms.

Wound biofilm infections caused by multidrug-resistant (MDR) bacteria constitute a major threat to public health; acquired resistance combined with resistance associated with the biofilm phenotype makes combatting these infections challenging. Biodegradable polymeric nanoemulsions that encapsulate two hydrophobic antimicrobial agents (eugenol and triclosan) (TE-BNEs) as a strategy to combat chronic wound infections are reported here. The cationic nanoemulsions efficiently penetrate and accumulate in biofilms, synergistically eradicating MDR bacterial biofilms, including persister cells.

Nanotherapeutics using all-natural materials. Effective treatment of wound biofilm infections using crosslinked nanoemulsions.

Bacterial wound infections are a threat to public health. Although antibiotics currently provide front-line treatments for bacterial infections, the development of drug resistance coupled with the defenses provided through biofilm formation render these infections difficult, if not impossible, to cure. Antimicrobials from natural resources provide unique antimicrobial mechanisms and are generally recognized as safe and sustainable.

Polymeric Nanoparticles Active against Dual-Species Bacterial Biofilms.

Biofilm infections are a global public health threat, necessitating new treatment strategies. Biofilm formation also contributes to the development and spread of multidrug-resistant (MDR) bacterial strains. Biofilm-associated chronic infections typically involve colonization by more than one bacterial species.

Biodegradable Poly(lactic acid) Stabilized Nanoemulsions for the Treatment of Multidrug-Resistant Bacterial Biofilms.

Biofilm infections caused by multidrug-resistant (MDR) bacteria are an urgent global health threat. Incorporation of natural essential oils into biodegradable oil-in-water cross-linked polymeric nanoemulsions (X-NEs) provides effective eradication of MDR bacterial biofilms. The X-NE platform combines the degradability of functionalized poly(lactic acid) polymers with the antimicrobial activity of carvacrol (from oregano oil).

Activity of Biodegradable Polymeric Nanosponges against Dual-Species Bacterial Biofilms.

Infections caused by multidrug-resistant (MDR) bacteria present an emerging global health crisis, and the threat is intensified by the involvement of biofilms. Some biofilm infections involve more than one species; this can further challenge treatment using traditional antibiotics. Nanomaterials are being developed as alternative therapeutics to traditional antibiotics; here we report biodegradable polymer-stabilized oil-in-water nanosponges (BNS) and show their activity against dual-species bacterial biofilms.

Nanomaterial-based therapeutics for antibiotic-resistant bacterial infections.

Antibiotic-resistant bacterial infections arising from acquired resistance and/or through biofilm formation necessitate the development of innovative 'outside of the box' therapeutics. Nanomaterial-based therapies are promising tools to combat bacterial infections that are difficult to treat, featuring the capacity to evade existing mechanisms associated with acquired drug resistance. In addition, the unique size and physical properties of nanomaterials give them the capability to target biofilms, overcoming recalcitrant infections.

Titanium Carbide Nanofibers-Reinforced Aluminum Compacts, a New Strategy to Enhance Mechanical Properties.

TiC nanofibers reinforced Al matrix composites were produced by High Frequency Induction Heat Sintering (HFIHS).The titanium carbide nanofibers with an average diameter of 90 nm are first prepared by electrospinning technique and high temperature calcination process. A composite solution containing polyacrylonitrile and titanium isopropoxide is first electrospun into the nanofibers, which are subsequently stabilized and then calcined to produce the desired TiC nanofibers.

Study of depression among a sample of hypertensive patients.

Hypertension is one of the commonest diseases worldwide. Hypertension (HTN) or high blood pressure, sometimes called arterial hypertension, is a chronic medical condition, which elevated blood pressure in the arteries. This forces the heart to work harder than normal to circulate blood via the blood vessels.