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Background: Colorectal cancer [CRC] is among the most fatal types of cancer. An active targeting delivery system that specifically interacts with CRC cells could improve the therapy's outcomes. Herein, Cetuximab single-chain fragment variable antibody [scFv] fragments were conjugated to the surface of 5-FU encapsulated chitosan nanoparticles [CS NPs] to develop an effective therapeutic platform [scFv-CS/5-FU NPs]., Method: CS/5-FU NPs were synthesized using a special fluidic system. Encapsulation efficiency [EE], loading capacity [LC], and the drug release profile of the particles were determined. scFv fragments were produced recombinantly and tailored on the surface of CS/5-FU NPs. The physicochemical features of scFv-CS/5-FU NPs were also characterized. MTT and flow cytometry assay investigated the toxicity effect of scFv-CS/5-FU NPs on the HCT116 cell line., Results: CS/5-FU NPs had a homogenous spherical shape. They possessed sustainable drugrelease behavior. The produced scFv-CS/5-FU NPs were also spherical. scFv-CS/5-FU NPs significantly decreased the viability of cancerous cells in a dose-dependent manner and induced apoptosis in 97.97% of targeted cells., Conclusion: scFv-CS/5-FU NPs showed remarkable anti-CRC activity. This novel targeting delivery system reduced the effective dose of 5-FU which is of vital importance to decrease the devastating side effects of chemotherapy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Persistent mineralocorticoid receptor activation is a pathologic response in type 2 diabetes and chronic kidney disease. Whereas mineralocorticoid receptor antagonists are beneficial in reducing cardiovascular complications, direct mechanistic pathways for these effects in humans are lacking., Methods: The MAGMA trial (Mineralocorticoid Receptor Antagonism Clinical Evaluation in Atherosclerosis) was a randomized, double-blind, placebo-controlled trial in patients with high-risk type 2 diabetes with chronic kidney disease (not receiving dialysis) on maximum tolerated renin-angiotensin system blockade. The primary end point was change in thoracic aortic wall volume, expressed as absolute or percent value (ΔTWV or ΔPWV), using 3T magnetic resonance imaging at 12 months. Secondary end points were changes in left ventricle (LV) mass; LV fibrosis, measured as a change in myocardial native T1; and 24-hour ambulatory and central aortic blood pressures. Tertiary end points included plasma proteomic changes in 7596 plasma proteins using an aptamer-based assay., Results: A total of 79 patients were randomized to placebo (n=42) or 25 mg of spironolactone daily (n=37). After a modified intent-to-treat, including available baseline data of study end points, patients who completed the trial protocol were included in the final analyses. At the 12-month follow-up, the average change in PWV was 7.1±10.7% in the placebo group and 0.87±10.0% in the spironolactone group ( P =0.028), and ΔTWV was 1.2±1.7 cm 3 in the placebo group and 0.037±1.9 cm 3 in the spironolactone group ( P =0.022). Change in LV mass was 3.1±8.4 g in the placebo group and -5.8±8.4 g in the spironolactone group ( P =0.001). Changes in LV T1 values were significantly different between the placebo and spironolactone groups (26.0±41.9 ms in the placebo group versus a decrease of -10.1±36.3 ms in the spironolactone group; P =6.33×10 -4 ). Mediation analysis revealed that the spironolactone effect on thoracic aortic wall volume and myocardial mass remained significant after adjustment for ambulatory and central blood pressures. Proteomic analysis revealed a dominant effect of spironolactone on pathways involving oxidative stress, inflammation, and leukocyte activation., Conclusions: Among patients with diabetes with moderate to severe chronic kidney disease at elevated cardiovascular risk, treatment with spironolactone prevented progression of aortic wall volume and resulted in regression of LV mass and favorable alterations in native T1, suggesting amelioration of left-ventricular fibrosis., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02169089., Competing Interests: Dr Connelly holds the Keenan Chair in Research Leadership at St Michael’s Hospital and University of Toronto.

Objective: The anticancer properties of recombinant α-luffin (LUF) are wellestablished. However, the cytotoxic effects of encapsulating LUF within niosomes on the SKBR3 breast cancer cell line have yet to be explored. Our study aimed to investigate whether this encapsulation strategy could improve cytotoxic effects., Methods: Alpha-luffin was expressed, purified, and refolded. Then, this protein was utilized to craft an optimal formulation, guided by experimental design. In this work, we have explored various physicochemical properties, including particle size, polydispersity index, zeta potential, morphology, entrapment efficiency, drug release and kinetics, storage stability, and FTIR spectroscopy. Additionally, we have assessed the cellular uptake and cytotoxic effect of the optimized niosome formulation on the SKBR3 breast cancer cell line., Results: The optimized niosome exhibited a mean diameter of 315±6.4 nm (DLS). Successful encapsulation of LUF into regularly shaped, spherical niosomes was achieved, with an encapsulation efficiency of 73.45±2.4%. Notably, Niosomal LUF (NLUF) exhibited significantly increased cytotoxicity against SKBR3 cells., Conclusion: These findings suggest that niosomes loaded with LUF hold promise as a potential treatment strategy for breast cancer., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Granulocyte colony-stimulating factor (GCSF) stimulates the proliferation of neutrophils but it has low serum half-life. Therefore, the present study was done to investigate the effect of XTENylation on biological activity, pharmacokinetics, and pharmacodynamics of GCSF in a neutropenic rat model. XTEN tag was genetically fused to the N-terminal region of GCSF-encoding gene fragment and subcloned into pET28a expression vector. The cytoplasmic expressed recombinant protein was characterized through intrinsic fluorescence spectroscopy (IFS), dynamic light scattering (DLS), and size exclusion chromatography (SEC). In vitro biological activity of the XTEN-GCSF protein was evaluated on NFS60 cell line. Hematopoietic properties and pharmacokinetics were also investigated in a neutropenic rat model. An approximately 140 kDa recombinant protein was detected on SDS-PAGE. Dynamic light scattering and size exclusion chromatography confirmed the increase in hydrodynamic diameter of GCSF molecule after XTENylation. GCSF derivatives showed efficacy in proliferation of NFS60 cell line among which the XTEN-GCSF represented the lowest EC 50 value (100.6 pg/ml). Pharmacokinetic studies on neutropenic rats revealed that XTEN polymer could significantly increase protein serum half-life in comparison with the commercially available GCSF molecules. PEGylated and XTENylated GCSF proteins were more effective in stimulation of neutrophils compared to the GCSF molecule alone. XTENylation of GCSF represented promising results in in vitro and in vivo studies. This approach can be a potential alternative to PEGylation strategies for increasing serum half-life of protein., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)