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Nanotechnology offers a novel strategy for enhancing the susceptibility of pathogens resistant to traditional antibiotics. Another effective strategy is combination therapy, where multiple agents are used together to improve treatment efficacy. In this study, both nanoparticle-based formulation and combinatorial therapy were utilized to develop a potent antibacterial system targeting infectious bacteria. Lysozyme (Lys) and Vancomycin (Van) were co-loaded onto mesoporous silica nanoparticles (MSNs), forming Lys-Van-MSNs. The antimicrobial activity of these nanoparticles was evaluated by determining the minimum inhibitory concentration (MIC) against Staphylococcus aureus . The MIC values for Lys-Van-MSNs were 0.85 µg/ml for Van and 0.168 mg/ml for Lys, reflecting reductions of 86.4% and 93.7%, respectively, compared to the free forms. Additionally, cytotoxicity was tested using MTT, ROS, and hemolysis assays on human cell lines (breast, fibroblast, and AGS), showing over 80% cell viability, indicating minimal toxicity. The MSN-based formulation, with its synergistic antibacterial effects, reduced drug dosage, and high biocompatibility, offers a practical and effective solution for addressing bacterial infections.

The lipase-immobilized polyethyleneimine (PEI)- and polyacrylic acid (PAA)–coated magnetic silica nanocomposite particles (L-PEI-MS and L-PAA-MS, respectively) were prepared and applied at various transesterification reaction conditions. The reactions were carried out with soybean, sunflower, canola, and palm oils along with methanol or ethanol in the solvent-free and n-hexane systems. The highest fatty acid methyl ester (FAME) and fatty acid ethyl ester (FAEE) synthesis yields were obtained from the transesterification of palm oil, i.e., almost 7.7–10.2% higher than other oils. At the constant reaction conditions, the application of ethanol leads to higher (6.0–8.7%) reaction yields in comparison with methanol. In addition, irrespective of reaction conditions, the best performance was acquired by L-PEI-MS; e.g., the FAME and FAEE synthesis yield values of 81.2% and 88.3% were obtained from transesterification of palm oil in the solvent-free systems, respectively. Addition of n-hexane improved the synthesis of FAME and FAEE yield values to 88.9% and 93.3%, respectively, using L-PEI-MS. The transesterification reactions kinetics follows the Ping-Pong Bi-Bi mechanism with alcohol inhibition effects. The high catalytic performance of L-PEI-MS might be related to its hydrophobic nature, which enhances the accessibility of oil molecules to the immobilized lipases and hampers the deactivating effect of alcohol molecules on them.

SARS-CoV-2 (SCV2) has posed significant global challenges, necessitating improved immunization strategies to enhance protection and mitigate disease severity. Combining Bacille Calmette-Guérin (BCG) with SCV2 vaccine shows potential due to BCG’s immunomodulatory properties and ability to induce trained immunity. This study evaluates the efficacy of a combined BCG and SCV2 vaccine regimen in enhancing immune responses, controlling viral load, and reducing lung pathology following a live SCV2 challenge in a Syrian hamster model. In this controlled, randomized study, hamsters were divided into six groups and immunized with various BCG and SCV2 vaccine regimens. Hamsters were randomized into six groups: Group A received a high dose of BCG (5 × 10⁶ CFU) plus SCV2 vaccine on Days 0 and 14; Group B (control) received PBS; Group C received BCG alone; Group D received SCV2 vaccine alone; Group E received a BCG/SCV2 combination on Day 0 and SCV2 booster on Day 14; Group F received a low BCG dose (5 × 10³ CFU) plus SCV2 on both days. Post-challenge, weight changes, lung histopathology, neutralizing antibody titers, and viral load were assessed using qRT-PCR, TCID 50 , and histological scoring to evaluate immunogenicity, viral control, and tissue damage. Post-challenge, Group A (Combined BCG [5 × 10 6 CFU] and SCV2 vaccine on Day 0 and Day 14 as a booster) demonstrated stable weights and the strongest neutralizing antibody titers, effectively suppressing viral replication and showing minimal lung pathology ( P  < 0.05). In contrast, the control group (B) exhibited significant weight loss, high viral loads, and severe lung damage. Groups C, D, E, and F showed varying degrees of immune responses and pathology, with Group F (BCG [5 × 10 3 CFU]) performing better than others but less effectively than Group A. The present investigation findings highlight the potential of a combined BCG and SCV2 vaccination strategy with an emphasis on dose to provide robust protection against severe COVID-19 outcomes and underscore the role of BCG as an immunological adjuvant to improve vaccine efficacy.

ObjectivesThe yeast cells were coated with Fe3O4 magnetic nanoparticles and employed as biocatalyst for the microbial biotransformation of benzaldehyde into l-phenylacetylcarbinol (l-PAC).ResultsSaccharomyces cerevisiae CEN.PK113-7D yeast cells were coated with magnetic nanoparticles to facilitate the cells separation process. Transmission electron microscopy, powder XRD diffraction, and vibrating sample magnetometer were used to characterize magnetic nanoparticles and magnetic nanoparticle-coated yeast cells. Then the reusability of magnetically recoverable cells in production of l-PAC was investigated. Results show that coating yeast cells with magnetic nanoparticles does not affect their size and structure. Coated cells were also used in seven consecutive batch cycles and no significant reduction for l-PAC titer was observed in any of the cycles.ConclusionCoating yeast cells with magnetic nanoparticles enabled rapid separation and reuse of cells in several successive batch cycle without affecting their ability to produce l-PAC.

Novel nanofibers from blends of polylactic-co-glycolic acid (PLGA) and chitosan have been produced through an emulsion electrospinning process. The spinning solution employed polyvinyl alcohol (PVA) as the emulsifier. PVA was extracted from the electrospun nanofibers, resulting in a final scaffold consisting of a blend of PLGA and chitosan. The fraction of chitosan in the final electrospun mat was adjusted from 0 to 33%. Analyses by scanning and transmission electron microscopy show uniform nanofibers with homogenous distribution of PLGA and chitosan in their cross section. Infrared spectroscopy verifies that electrospun mats contain both PLGA and chitosan. Moreover, contact angle measurements show that the electrospun PLGA/chitosan mats are more hydrophilic than electrospun mats of pure PLGA. Tensile strengths of 4.94 MPa and 4.21 MPa for PLGA/chitosan in dry and wet conditions, respectively, illustrate that the polyblend mats of PLGA/chitosan are strong enough for many biomedical applications. Cell culture studies suggest that PLGA/chitosan nanofibers promote fibroblast attachment and proliferation compared to PLGA membranes. It can be assumed that the nanofibrous composite scaffold of PLGA/chitosan could be potentially used for skin tissue reconstruction.

Development of tissue engineering scaffolds with native-like biology and microarchitectures is a prerequisite for stem cell mediated generation of off-the-shelf-tissues. So far, the field of tissue engineering has not full-filled its grand potential of engineering such combinatorial scaffolds for engineering functional tissues. This is primarily due to the many challenges associated with finding the right microarchitectures and ECM compositions for optimal tissue regeneration. Here, we have developed a new microgel array to address this grand challenge through robotic printing of complex stem cell-laden microgel arrays. The developed microgel array platform consisted of various microgel environments that where composed of native-like cellular microarchitectures resembling vascularized and bone marrow tissue architectures. The feasibility of our array system was demonstrated through localized cell spreading and osteogenic differentiation of human mesenchymal stem cells (hMSCs) into complex tissue-like structures. In summary, we have developed a tissue-like microgel array for evaluating stem cell differentiation within complex and heterogeneous cell microenvironments. We anticipate that the developed platform will be used for high-throughput identification of combinatorial and native-like scaffolds for tissue engineering of functional organs.

Objectives It has been shown that growth factors and small molecules play an essential role in the proliferation of β cells and insulin production. In this study, we investigated the effects of small molecules (WS6 and 5-iodotubercidin) and growth factors (TGFβ, HGF, and EGF) on the proliferation of β-like human ipSCs. Methods iPSCs derived β cells were treated with small molecules and growth factors. Cytotoxic activity of small molecules and growth factors was determined using MTT assay. Insulin gene expression and secretion were measured by qPCR and ELISA, respectively. The protein expression of insulin was evaluated by western blot as well. Results Simltananeous addition of WS6 and Harmine into the culture media increased insulin gene expression compared to treatment by each molecule alone ( p  < 0.05). It was found that the simultaneous recruitment of EGH, HGF, and TGF-β increased insulin expression compared to treatment by each molecule alone ( p  < 0.05). Results showed that EGF, HGF, TGF-β growth factors increased insulin gene expression, eventually leading to insulin secretion from β cells ( p  < 0.05). Conclusions Growth factors and small molecules synergistically enhanced the proliferation of β cells and insulin production.

Objectives It has been shown that growth factors and small molecules play an essential role in the proliferation of [beta] cells and insulin production. In this study, we investigated the effects of small molecules (WS6 and 5-iodotubercidin) and growth factors (TGF[beta], HGF, and EGF) on the proliferation of [beta]-like human ipSCs. Methods iPSCs derived [beta] cells were treated with small molecules and growth factors. Cytotoxic activity of small molecules and growth factors was determined using MTT assay. Insulin gene expression and secretion were measured by qPCR and ELISA, respectively. The protein expression of insulin was evaluated by western blot as well. Results Simltananeous addition of WS6 and Harmine into the culture media increased insulin gene expression compared to treatment by each molecule alone (p < 0.05). It was found that the simultaneous recruitment of EGH, HGF, and TGF-[beta] increased insulin expression compared to treatment by each molecule alone (p < 0.05). Results showed that EGF, HGF, TGF-[beta] growth factors increased insulin gene expression, eventually leading to insulin secretion from [beta] cells (p < 0.05). Conclusions Growth factors and small molecules synergistically enhanced the proliferation of [beta] cells and insulin production. Keywords: Human induced pluripotent stem cells, Insulin, WS6, Harmine, Growth factor

Background Lung cancer is a common and deadly disease. Chemotherapy is the most common treatment, which inhibits cancer cell growth. Pemetrexed (PMX) is often used with other drugs. Environmental stress can affect regulatory non-coding RNAs such as MicroRNAs that modify gene expression. This study investigates the effect of PMX on the hsa-miR-320a-3p expression in the Calu-6 lung cancer cell line. Methods and result Calu-6 cells were cultured in an incubator with 37 °C, 5% CO2, and 98% humidity. The MTT test was performed to determine the concentration of PMX required to inhibit 50% of cell growth. To examine growth inhibition and apoptosis, release of lactate dehydrogenase (LDH), cell assays and caspase 3 and 7 enzyme activity were used. Finally, molecular studies were conducted to compare the expression of hsa-miR-320a-3p and genes including VDAC1, DHFR, STAT3, BAX and BCL2 before and after therapy. Results According to a study, it has been observed that PMX therapy significantly increases LDH release after 24 h. The study found that PMX's IC 50 on Calu-6 is 8.870 µM. In addition, the treated sample showed higher expression of hsa-miR-320a-3p and BAX , while the expression of VDAC1, STAT3, DHFR and BCL2 decreased compared to the control sample. Conclusion According to the findings of the current research, hsa-miR-320a-3p seems to have the potential to play an important role in the development of novel approaches to the treatment of lung cancer.

Preparation of novel nanocomposite particles (NCPs) with high visible-light-driven photocatalytic activity and possessing recovery potential after advanced oxidation process (AOP) is much desired. In this study, pure anatase phase titania (TiO₂) nanoparticles (NPs) as well as three types of NCPs including nitrogen-doped titania (TiO₂-N), titania-coated magnetic silica (Fe₃O₄ cluster@SiO₂@TiO₂ (FST)), and a novel magnetically recoverable TiO₂ nanocomposite photocatalyst containing nitrogen element (Fe₃O₄ cluster@SiO₂@TiO₂-N (FST-N)) were successfully synthesized via a sol–gel process. The photocatalysts were characterized by X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy, field emission scanning electron microscopy (FE-SEM) with an energy-dispersive X-ray (EDX) spectroscopy analysis, X-ray photoelectron spectroscopy (XPS), UV–vis diffuse reflectance spectroscopy (DRS), and vibrating sample magnetometer (VSM). The photocatalytic activity of as-prepared samples was further investigated and compared with each other by degradation of phenol, as a model for the organic pollutants, in deionized (DI) water under visible light irradiation. The TiO₂-N (55 ± 1.5 %) and FST-N (46 ± 1.5 %) samples exhibited efficient photocatalytic activity in terms of phenol degradation under visible light irradiation, while undoped samples were almost inactive under same operating conditions. Moreover, the effects of key operational parameters, the optimum sample calcination temperature, and reusability of FST-N NCPs were evaluated. Under optimum conditions (calcination temperature of 400 °C and near-neutral reaction medium), the obtained results revealed efficient degradation of phenol for FST-N NCPs under visible light irradiation (46 ± 1.5 %), high yield magnetic separation and efficient reusability of FST-N NCPs (88.88 % of its initial value) over 10 times reuse.