21 research outputs found
Print-and-Peel Fabrication for Microfluidics: What’s in it for Biomedical Applications?
Modification Strategies of Kapok Fiber Composites and Its Application in the Adsorption of Heavy Metal Ions and Dyes from Aqueous Solutions: A Systematic Review
Kapok fiber (Ceiba pentandra) belongs to a group of natural fibers that are mainly composed of cellulose, lignin, pectin, and small traces of inorganic compounds. These fibers are lightweight with hollow tubular structure that is easy to process and abundant in nature. Currently, kapok fibers are used in industry as filling material for beddings, upholstery, soft toys, and nonwoven materials. However, kapok fiber has also a potential application in the adsorptive removal of heavy metal ions and dyes from aqueous systems. This study aims to provide a comprehensive review about the recent developments on kapok fiber composites including its chemical properties, wettability, and surface morphology. Effective and innovative kapok fiber composites are analyzed with the help of characterization tools such as scanning electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, thermogravimetric analysis, Fourier transform infrared spectroscopy, energy-dispersive X-ray spectroscopy, and Brunauer-Emmett-Teller analysis. Different pre-treatment methods such as alkali and acid pre-treatment, oxidation pre-treatment, and Fenton reaction are discussed. These techniques are applied to enhance the hydrophilicity and to generate rougher fiber surfaces. Moreover, surface modification and synthesis of kapok fiber-based composites and its environmental applications are examined. There are various methods in the fabrication of kapok fiber composites that include chemical modification and polymerization. These procedures allow the kapok fiber composites to have higher adsorption capacities for selective heavy metal and dye removal.</jats:p
Nanozeolite-Impregnated Polysulfone/Polyethylene Glycol Nanocomposite Membrane for Ion Adsorption Application
Polysulfone (PSf) is a high-performance polymer often used in water treatment applications. Polyethylene glycol (PEG) and Nanozeolite (NZ) were used as additives to improve the membrane’s porosity, chemistry, and overall performance in ion adsorption. PSf, PSf with PEG, and PSf with PEG and varying concentrations of Nanozeolite were prepared via non-solvent induced phase separation (NIPS) and tested using: Scanning Electron Microscopy (SEM) for the surface morphology, Fourier Transform Infrared Spectroscopy (FTIR) for the chemical composition, Contact Angle Goniometer for the wettability, Zeta Potential for the stability, and conductivity test through salt-water bath for ion adsorption application.</jats:p
Zetomipzomib (KZR-616) attenuates lupus in mice via modulation of innate and adaptive immune responses
Zetomipzomib (KZR-616) is a selective inhibitor of the immunoproteasome currently undergoing clinical investigation in autoimmune disorders. Here, we characterized KZR-616 in vitro and in vivo using multiplexed cytokine analysis, lymphocyte activation and differentiation, and differential gene expression analysis. KZR-616 blocked production of &gt;30 pro-inflammatory cytokines in human peripheral blood mononuclear cells (PBMCs), polarization of T helper (Th) cells, and formation of plasmablasts. In the NZB/W F1 mouse model of lupus nephritis (LN), KZR-616 treatment resulted in complete resolution of proteinuria that was maintained at least 8 weeks after the cessation of dosing and was mediated in part by alterations in T and B cell activation, including reduced numbers of short and long-lived plasma cells. Gene expression analysis of human PBMCs and tissues from diseased mice revealed a consistent and broad response focused on inhibition of T, B, and plasma cell function and the Type I interferon pathway and promotion of hematopoietic cell lineages and tissue remodeling. In healthy volunteers, KZR-616 administration resulted in selective inhibition of the immunoproteasome and blockade of cytokine production following ex vivo stimulation. These data support the ongoing development of KZR-616 in autoimmune disorders such as systemic lupus erythematosus (SLE)/LN.</jats:p
Fabrication and Characterization of Electrospun Polysulfone (PSf) / Halloysite (HAL) Nanocomposite Membrane
B-PO05-007 RAPID AND ROBUST MAPPING OF CLINICAL DATA ON PERSONALIZED VOLUMETRIC ATRIAL GEOMETRIES
Preclinical evaluation of KZR-261, a novel small molecule inhibitor of Sec61.
3582 Background: Secreted and transmembrane proteins play key roles in malignant transformation and growth, including in autocrine growth factor expression, receptor oncogene signaling, and immune system evasion. Biogenesis of these proteins involves translocation of the nascent polypeptides into the endoplasmic reticulum (ER) through the Sec61 channel, providing an untapped therapeutic target for a broad spectrum of malignancies. Here we describe preclinical activity of KZR-261 and related inhibitors of Sec61-dependent protein secretion. Methods: Sec61 inhibition with KZR-261 and related analog KZR-834 were evaluated using cell lines overexpressing proteins of interest tagged with luciferase. In vitro anti-tumor activity was assessed against a panel of 346 cell lines across 25 tumor types. Quantitative proteomic profiling by mass spec and gene expression profiling by RNAseq were conducted following treatment in multiple solid and heme tumor cell lines. Anti-tumor efficacy was evaluated in athymic nude mice implanted with the cancer cell lines H82 (SCLC), HT29 (CRC), BxPC3 (Pancreatic), 22RV1 (Prostate), H929 (Myeloma) and RL (NHL). Activity was also evaluated in a MC38 syngeneic colon tumor model. Results: KZR-261 and KZR-834 exhibited nanomolar potency against many therapeutic targets, including immune checkpoints, VEGF-A, VEGFR and EGFR. Broad in vitro anti-cancer activity was observed with KZR-834, which potently decreased cell viability across both solid and heme tumor types including CRC, Pancreatic, HNSCC, HCC, Lymphoma and Myeloma. Global proteomic analysis observed more than 1.5 fold downregulation of < 10% of detected Sec61 client proteins following treatment, while gene expression profiling revealed upregulation of ER stress response genes in sensitive versus resistant cell lines. Analysis of the TCGA database also found these genes upregulated in a number of different tumor types. In vivo, weekly IV administration was well tolerated and induced a dose dependent anti-tumor response at doses below the MTD in solid and heme xenograft models. In the syngeneic MC38 model, administration of KZR-834 in combination with anti-PD1 antibody resulted in greater anti-tumor activity than either single agent. Conclusions: Novel Sec61 inhibitors potently block expression of secreted and membrane proteins, translating into anti-tumor activity against many tumor types in vitro and in vivo, suggesting broad therapeutic potential. Clinical trials are being planned with KZR-261 to understand safety and early efficacy of this novel compound and therapeutic target. </jats:p
