Engineering of redox-triggered polymeric lipid hybrid nanocarriers for selective drug delivery to cancer cells.

Tunable redox-sensitive polymeric-lipid hybrid nanocarriers (RS-PLHNCs) were fabricated using homogenization and nanoprecipitation methods. These nanocarriers were composed of novel redox-cholesterol with disulfide linkages and synthesized by conjugating cholesterol with dithiodipropionic acid esterification. Berberine (BBR) was loaded into the fabricated nanocarriers to investigate the selective uptake of BBR by cancer cells as well as its release and enhanced cytotoxicity.

Peptaloid: A Comprehensive Database for Exploring Peptide Alkaloid.

Peptaloid is the first dedicated database for peptide alkaloid molecules, a unique class of naturally derived compounds known for their structural diversity and significant biological activities. Despite their promising potential in drug discovery and therapeutic development, research on peptide alkaloids has been limited by the absence of a comprehensive and centralized resource. Fragmented data across various sources have posed a significant challenge, underscoring the need for a specialized database to facilitate more efficient research and application.

Dual drug nanoparticle synergistically induced apoptosis, suppressed inflammation, and protected autophagic response in rheumatoid arthritis fibroblast-like synoviocytes.

Rheumatoid arthritis (RA) is a chronic immune-mediated joint inflammatory disorder associated with aberrant activation of fibroblast-like synoviocytes (FLS). Recently, FLS gained importance due to its crucial role in RA pathogenesis, and thus, targeting FLS is suggested as an attractive treatment strategy for RA. FLS-targeted approaches may be combined with disease-modifying antirheumatic drugs (DMARDs) and natural phytochemicals to improve efficacy in RA control and negate immunosuppression.

Palladium Nanocapsules for Photothermal Therapy in the Near-Infrared II Biological Window.

Recent developments in nanomaterials with programmable optical responses and their capacity to modulate the photothermal effect induced by an extrinsic source of light have elevated plasmonic photothermal therapy (PPTT) to the status of a favored treatment for a variety of malignancies. However, the low penetration depth of near-infrared-I (NIR-I) lights and the need to expose the human body to a high laser power density in PPTT have restricted its clinical translation for cancer therapy. Most nanostructures reported to date exhibit limited performance due to (i) activity only in the NIR-I region, (ii) the use of intense laser, (iii) need of large concentration of nanomaterials, or (iv) prolonged exposure times to achieve the optimal hyperthermia state for cancer phototherapy.

Quaternary Pullulan-Functionalized 2D MoS Glycosheets: A Potent Bactericidal Nanoplatform for Efficient Wound Disinfection and Healing.

Rapid emergence of multidrug-resistant bacterial strains has posed a global threat to public health. Hospital-acquired infections, especially in diabetic and burn patients, severely impede the process of wound healing, thereby causing high mortality. This calls for developing a new biomaterial that synergistically destroys pathogenic strains and also helps in promoting wound healing without causing any resistance generation.

Formulation of a dual drug-loaded nanoparticulate co-delivery hydrogel system and its validation in rheumatoid arthritis animal model.

Rheumatoid arthritis (RA), a systemic autoimmune disease that dramatically affects patients' quality of life. Given the intricacy of RA's pathophysiology, no single treatment can completely halt the disease progression. Here, we attempted to treat RA holistically and synergistically by co-delivering methotrexate (MTX), a standard slow-acting anti-rheumatic drug, and phenethyl isothiocyanate (PEITC), a bioactive phytochemical, using a sodium alginate (SA)-pluronic F127 (PF-127) hydrogel formulation.

Thermosensitive smart hydrogel of PEITC ameliorates the therapeutic efficacy in rheumatoid arthritis.

Rheumatoid arthritis (RA) is an autoimmune condition that accompanies chronic inflammation of joints with limited therapeutic options. Phenethyl isothiocyanate (PEITC), a bioactive phytochemical, exerts its chemopreventive, anti-oxidant, and anti-inflammatory activity via the Nrf-2 pathway. However, limited water solubility, short half-life, and instability are reasons for the low bioavailability of PEITC that hampers clinical application.

Quaternary ammonium substituted pullulan accelerates wound healing and disinfects infected wounds in mouse through an atypical 'non-pore forming' pathway of bacterial membrane disruption.

The emergence of multi-drug resistant pathogens has fueled the search for alternatives to the existing line of antibiotics that can eradicate pathogens without inducing resistance development. Here, we report the accelerated wound healing and disinfection potential of a non-amphiphilic quaternized fungal exopolysaccharide, pullulan, without resistance generation in pathogens. The quaternary ammonium substituted pullulan (CP) derivatives showed excellent bactericidal activity against both Gram negative (MBC = 1.

Naringin as Sustained Delivery Nanoparticles Ameliorates the Anti-inflammatory Activity in a Freund's Complete Adjuvant-Induced Arthritis Model.

Naringin (NAR), a naturally occurring essential flavonoid, present in grapefruit and Chinese herbal medicines, creates great interest in researchers due to its diverse biological and pharmacological activities. However, further development of NAR is hindered due to its poor water solubility and dissolution rates in GIT. To address these limitations, in this study, we report polymeric nanoparticles (NPs) of NAR (NAR-PLGA-NPs) for enhancing the oral NAR efficiency, with a biodegradable polymer (PLGA) to improve its absorption and bioavailability.

Correction to Naringin in Combination with Isothiocyanates as Liposomal Formulations Potentiates the Anti-inflammatory Activity in Different Acute and Chronic Animal Models of Rheumatoid Arthritis.

[This corrects the article DOI: 10.1021/acsomega.0c04300.

Naringin in Combination with Isothiocyanates as Liposomal Formulations Potentiates the Anti-inflammatory Activity in Different Acute and Chronic Animal Models of Rheumatoid Arthritis.

Combination of drugs is extensively used to treat chronic inflammatory disease. Naringin (NAR), sulforaphane (SFN), and phenethyl isothiocyanate (PEITC) are nutraceuticals with promising anti-inflammatory properties. However, their clinical effectiveness gets hindered because of low aqueous solubility and poor bioavailability.

Molecular characterization, tissue distribution and differential nutritional regulation of putative Elovl5 elongase in silver barb (Puntius gonionotus).

Fatty acid desaturase (Fads) and elongase (Elovl) are two important enzymes involved in the biosynthesis of long-chain polyunsaturated fatty acids (LC-PUFAs) in fishes. Silver barb (Puntius gonionotus) is considered a promising medium carp species for freshwater aquaculture in Asia. Earlier, Δ6 fads cDNA was characterized to understand the molecular mechanism of LC-PUFA biosynthesis in this species.

Selection of P-Glycoprotein Inhibitor and Formulation of Combinational Nanoformulation Containing Selected Agent Curcumin and DOX for Reversal of Resistance in K562 Cells.

Purpose: To select P-glycoprotein (P-gp) inhibitor from natural source for reversal of DOX resistance in K562 cells and to develop selected one in to nanoformulation in combination with DOX.

Methods: DOX resistant K562 (K562R) cells were developed and reversal of resistance by P-gp inhibitor was validated by co-treatment with verapamil. The p-gp inhibitors were evaluated for their potential to inhibit P-gp (calcein assay) and to reverse drug resistance (XTT cell viability assay).

Selection and optimization of nano-formulation of P-glycoprotein inhibitor for reversal of doxorubicin resistance in COLO205 cells.

Objective: The prime objective of current work was to develop a strategy for preparation of combinational nano-formulation for reversal of drug resistance.

Methods: As a model system, doxorubicin (DOX)-resistant COLO205 cells were developed and validated. From co-treatment studies with DOX, curcumin was selected as it reversed DOX-resistance at lowest concentration.

An Improved Comparative Docking Approach for Developing Specific Glycogen Phosphorylase Inhibitors Using Pentacyclic Triterpenes.

Background: Mitigation of unwanted effects is a major issue to be addressed in drug discovery. The human genome shares a considerable degree of sequence identity and structural homology whereby multiple binding pockets of similar composition is seen across different family of proteins. This distribution of similar binding pockets in different proteins is a major reason for cross reactivity upon ligand binding.

Comparative Study of Different Nano-Formulations of Curcumin for Reversal of Doxorubicin Resistance in K562R Cells.

Purpose: Curcumin is very well established as a chemo-therapeutic, chemo-preventive and chemo-sensitizing agent in diverse disease conditions. As the isolated pure form has poor solubility and pharmacokinetic problems, therefore it is encapsulated in to several nano-formulations to improve its bioavailability. Here in the current study, we aim to compare different nano-formulations of curcumin for their chemo-sensitizing activity in doxorubicin (DOX) resistant K562 cells.

Study of miRNA Based Gene Regulation, Involved in Solid Cancer, by the Assistance of Argonaute Protein.

Solid tumor is generally observed in tissues of epithelial or endothelial cells of lung, breast, prostate, pancreases, colorectal, stomach, and bladder, where several genes transcription is regulated by the microRNAs (miRNAs). Argonaute (AGO) protein is a family of protein which assists in miRNAs to bind with mRNAs of the target genes. Hence, study of the binding mechanism between AGO protein and miRNAs, and also with miRNAs-mRNAs duplex is crucial for understanding the RNA silencing mechanism.

Formulation and Optimization of Doxorubicin and Biochanin A Combinational Liposomes for Reversal of Chemoresistance.

Circumvention of drug resistance still remains a challenge in the development of anticancer therapeutics. Combinational nano-formulations provide many avenues for effective cancer therapy and reversal of drug resistance. In the current study, combination of biochanin A (BioA) and doxorubicin (DOX) in liposomes were prepared and studied for its potential to reverse DOX resistance in COLO205 cells.

Data on sulforaphane treatment mediated suppression of autoreactive, inflammatory M1 macrophages.

Any chronic, inflammatory, autoimmune disease (e.g. arthritis) associated pathogenesis directs uncontrolled accumulation of both soluble forms of collagens in the synovial fluids and M1 macrophages around inflamed tissues.

Sulforaphane regulates phenotypic and functional switching of both induced and spontaneously differentiating human monocytes.

At the site of inflammation, switching default on polarization of monocyte differentiation into classically activated macrophages (M1 type) is one of the pathogenic outcomes in several inflammatory autoimmune diseases, such as rheumatoid arthritis and osteoarthritis. In rheumatoid and osteoarthritis, a soluble collagen known as self-antigen is considered as a biomarker and acts as an important inflammatory mediator. In the present study, we investigated the effects of sulforaphane (SFN) on phenotypic changes and functional switching during in vitro induced and spontaneous differentiation of monocytes/macrophages, whose conditions were established with THP1 induced by PMA, and human peripheral blood monocytes, respectively.

In Silico Phylogenetic Analysis and Molecular Modelling Study of 2-Haloalkanoic Acid Dehalogenase Enzymes from Bacterial and Fungal Origin.

2-Haloalkanoic acid dehalogenase enzymes have broad range of applications, starting from bioremediation to chemical synthesis of useful compounds that are widely distributed in fungi and bacteria. In the present study, a total of 81 full-length protein sequences of 2-haloalkanoic acid dehalogenase from bacteria and fungi were retrieved from NCBI database. Sequence analysis such as multiple sequence alignment (MSA), conserved motif identification, computation of amino acid composition, and phylogenetic tree construction were performed on these primary sequences.

Hormetic Potential of Sulforaphane (SFN) in Switching Cells' Fate Towards Survival or Death.

Epidemiological evidences establish sulforaphane (SFN), a hormetic dietary isothiocyanate to be a promising chemopreventive, anti-inflammatory and anti-cancer agent. Beyond a concentration threshold SFN exerts pro-death activities (cell cycle arrest, epigenetic modifications and apoptosis) and below the threshold it either promotes prosurvival autophagy or remains latent. There is a significant lacuna in understanding the underpinning dynamic molecular networks that alternate the pharmacological responses with respect to the intracellular concentration and exposure time that renders SFN to be a characteristic hormetic molecule (display characteristic biphasic dose response curve).

In-silico gene co-expression network analysis in Paracoccidioides brasiliensis with reference to haloacid dehalogenase superfamily hydrolase gene.

Context: Paracoccidioides brasiliensis, a dimorphic fungus is the causative agent of paracoccidioidomycosis, a disease globally affecting millions of people. The haloacid dehalogenase (HAD) superfamily hydrolases enzyme in the fungi, in particular, is known to be responsible in the pathogenesis by adhering to the tissue. Hence, identification of novel drug targets is essential.

Application of bioinformatics tools and databases in microbial dehalogenation research (a review).

Microbial dehalogenation is a biochemical process in which the halogenated substances are catalyzed enzymatically in to their non-halogenated form. The microorganisms have a wide range of organohalogen degradation ability both explicit and non-specific in nature. Most of these halogenated organic compounds being pollutants need to be remediated; therefore, the current approaches are to explore the potential of microbes at a molecular level for effective biodegradation of these substances.