Metabolic reprogramming driven by EZH2 inhibition depends on cell-matrix interactions.

EZH2 (Enhancer of Zeste Homolog 2), a subunit of Polycomb Repressive Complex 2 (PRC2), catalyzes the trimethylation of histone H3 at lysine 27 (H3K27me3), which represses expression of genes. It also has PRC2-independent functions, including transcriptional coactivation of oncogenes, and is frequently overexpressed in lung cancers. Clinically, EZH2 inhibition can be achieved with the FDA-approved drug EPZ-6438 (tazemetostat). To realize the full potential of EZH2 blockade, it is critical to understand how cell-cell/cell-matrix interactions present in 3D tissue and cell culture systems influences this blockade in terms of growth-related metabolic functions. Here, we show that EZH2 suppression reduced growth of human lung adenocarcinoma A549 cells in 2D cultures but stimulated growth in 3D cultures. To understand the metabolic underpinnings, we employed [13C6]-glucose stable isotope-resolved metabolomics to determine the effect of EZH2 suppression on metabolic networks in 2D versus 3D A549 cultures. The Krebs cycle, neoribogenesis, γ-aminobutyrate metabolism, and salvage synthesis of purine nucleotides were activated by EZH2 suppression in 3D spheroids but not in 2D cells, consistent with the growth effect. Using simultaneous 2H7-glucose + 13C5,15N2-Gln tracers and EPZ-6438 inhibition of H3 trimethylation, we delineated the effects on the Krebs cycle, γ-aminobutyrate metabolism, gluconeogenesis, and purine salvage to be PRC2-dependent. Furthermore, the growth/metabolic effects differed for mouse Matrigel versus self-produced A549 extracellular matrix. Thus, our findings highlight the importance of the presence and nature of extracellular matrix in studying the function of EZH2 and its inhibitors in cancer cells for modeling the in vivo outcomes.

Evaluation of In Vitro Antimicrobial, Cytotoxic, Thrombolytic, and Antiarthritic Property of Different Parts of Bari Orchid.

Many different herbal extracts have historically been utilized to treat microbe-induced infections, injuries, cancer, thrombosis, and arthritis. The purpose of this study was to determine the antibacterial, cytotoxic, in vitro thrombolytic, and in vitro antiarthritic properties of ethanolic extracts of stem and seed of Bari orchid 1 (BO) plant. This orchid plant was developed by the Bangladesh Agriculture Research Institute (BARI) in Gazipur. Fourteen microbes were employed in the antimicrobial investigation, and samples of orchids were compared to ciprofloxacin as a reference. The BO/seed extract was found to possess more antibacterial activity. The lethality test of brine shrimps was used to assess the LC50 values. The BO/stem extract exhibited a higher cytotoxicity potential, in comparison to the BO/seed extract. Two concentrations (1000 and 100 ppm) and two incubation times (24 hours and 1.5 hours) were used to assess the thrombolytic activity of the extracts. Regarding the thrombolytic effect, the BO/stem extract has demonstrated greater promise. Furthermore, the herbal extract's antiarthritic activity was investigated at four different concentrations, and the results were evaluated in comparison with those of diclofenac sodium. When comparing BO/stem extract to other extracts, the greatest values for protein denaturation were obtained.

Field demonstration of irradiated sodium alginate as tea production booster.

Sodium alginate oligomers were tested for tea plant growth promoter and anti-fungal agent in this experiment. Sodium alginate solutions were irradiated by Co-60 gamma radiation with different radiation doses to produce the oligomers. Irradiated solutions were then diluted into 150, 300 and 500 ppm prior to foliar application. Solutions were applied through foliar spraying at 7 days interval and the best response of tea plants in terms of various attributes were recorded. Tea buds were collected in 10 days of interval and the growth attributes like- total number of buds, fresh weight of buds, average leaf area and weight per bud, weight of made tea etc. were calculated. The experiment was continued up to 12 weeks and the attributes were averaged to get results per plucking. 12 kGy radiation doses along with 300ppm solution showed the best results and about 36% increase in productivity was found based on the fresh weight of buds. Total fungal count in tea leaves was also found to be reduced greatly. Based on the present study, irradiated sodium alginate could be used as safe and environmentally friendly agent to increase tea production.

Gelatin-based instant gel-forming volatile spray for wound-dressing application.

This study was a successful endeavor to develop and investigate the suitability of a bioadhesive wound-healing gel based on gelatin for first-aid purposes. Polyethylene glycol (PEG) was used to prepare a denser phase of gelatin chains, and diethyl ether (DEE) was used to introduce high volatility to the solution. The prepared solution was stable in the storage container but rapidly formed (within 3 s) a protective and bioadhesive gel around the wound surface by being sprayed over the wound. Besides, it also suppressed pain and showed moderate antimicrobial activity against S. aureus. It was also found highly biocompatible and non-toxic. All the results revealed that the prepared solution could be an effective candidate for treating minor injuries or burn, especially for a first-aid purpose.

Development of Polymer-Assisted Nanoparticles and Nanogels for Cancer Therapy: An Update.

With cancer remaining as one of the main causes of deaths worldwide, many studies are undergoing the effort to look for a novel and potent anticancer drug. Nanoparticles (NPs) are one of the rising fields in research for anticancer drug development. One of the key advantages of using NPs for cancer therapy is its high flexibility for modification, hence additional properties can be added to the NPs in order to improve its anticancer action. Polymer has attracted considerable attention to be used as a material to enhance the bioactivity of the NPs. Nanogels, which are NPs cross-linked with hydrophilic polymer network have also exhibited benefits in anticancer application. The characteristics of these nanomaterials include non-toxic, environment-friendly, and variable physiochemical properties. Some other unique properties of polymers are also attributed by diverse methods of polymer synthesis. This then contributes to the unique properties of the nanodrugs. This review article provides an in-depth update on the development of polymer-assisted NPs and nanogels for cancer therapy. Topics such as the synthesis, usage, and properties of the nanomaterials are discussed along with their mechanisms and functions in anticancer application. The advantages and limitations are also discussed in this article.

Reinforcement of Gelatin-Based Nanofilled Polymer Biocomposite by Crystalline Cellulose from Cotton for Advanced Wound Dressing Applications.

This study is designed to extract crystalline cellulose from cotton and reinforcing gelatin film for biomedical applications, especially as a wound dressing material for its exceptional biocompatibility and bio-activity. Moreover, gelatin helps in wound healing and crystalline cellulose as additive can improve its properties. Crystalline cellulose was prepared through hydrolysis and the effects of crystalline cellulose loading on the morphology, mechanical properties, and water sensitivity of the nanocomposite were investigated by means of scanning electron microscopy, tensile strength testing, and water absorption testing. Developed biocomposite film showed homogeneous dispersion of crystalline cellulose within the gelatin matrix and strong interfacial adherence between the matrix and reinforcement. Samples were tested for biocompatibility and in vitro cytotoxicity and found to have excellent biocompatibility without having any cytotoxicity. In vivo wound healing study in an animal model showed 40% increased healing than the model dressed by conventional dressing.

Development of hydrocolloid Bi-layer dressing with bio-adhesive and non-adhesive properties.

Bio-active bi-layer thin film having both bio-adhesive and non-adhesive end composed of polyvinyl alcohol (PVA) and gelatin/chitosan/polyethylene glycol (PEG) blend was developed for biomedical applications especially as an alternative of advanced tissue scaffold. The developed composite film was subjected to mechanical, thermal and physico-chemical characterization such as tensile strength (TS) and elongation at break (Eb), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), fluid drainage capacity and biocompatibility. Suitable packaging was also selected and stability study and aging test of the composite film were performed after packing. The incorporation of chitosan and PEG into gelatin showed improved mechanical properties of both TS and Eb, which suggested the occurrence of interaction among gelatin, chitosan and PEG molecules in the composite film. The presence of crosslinking as an interaction of above three polymers was also confirmed by FTIR study. Results from the DSC study suggested increased thermal stability after crosslinking. On the other hand, water uptake studies suggested excellent fluid drainage capability and hydro-stability of the composite film. The proposed dressing also showed excellent biocompatibility. Based on the studies related to the performance with confirmed identity, we concluded that our developed bi-layer film is very potential as an ideal wound dressing material.

Fabrication and characterization of gelatin-based biocompatible porous composite scaffold for bone tissue engineering.

In this study, composite scaffolds were prepared with polyethylene oxide (PEO)-linked gelatin and tricalcium phosphate (TCP). Chitosan, a positively charged polysaccharide, was introduced into the scaffolds to improve the properties of the artificial bone matrix. The chemical and thermal properties of composite scaffolds were investigated by Fourier transform infrared spectroscopy, thermogravimetric analyzer, differential thermal analyzer. In vitro cytotoxicity of the composite scaffold was also evaluated and the sample showed no cytotoxic effect. The morphology was studied by SEM and light microscopy. It was observed that the prepared scaffold had an open interconnected porous structure with pore size of 230-354 µm, which is suitable for osteoblast cell proliferation. The mechanical properties were assessed and it was found that the composite had compressive modulus of 1200 MPa with a strength of 5.2 MPa and bending modulus of 250 MPa having strength of 12.3 MPa. The porosity and apparent density were calculated and it was found that the incorporation of TCP can reduce the porosity and water absorption. It was revealed from the study that the composite had a 3D porous microstructure and TCP particles were dispersed evenly among the crosslinked gelatin/chitosan scaffold.