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The development of effective antidiabetic agents remains a critical challenge in diabetes management. In this study, we introduce novel 1,2,4-triazole-based derivatives designed as dual inhibitors of α-amylase and α-glucosidase, key enzymes in carbohydrate metabolism. Molecular docking identified six promising candidates, with compounds 4 and 10 showing the highest potency. Both compounds exhibited strong α-glucosidase inhibition (IC 50  = 0.27 ± 0.01 µg/mL and 0.31 ± 0.01 μg/mL, respectively), surpassing acarbose, and also demonstrated potent α-amylase inhibition (IC 50  = 0.19 ± 0.01 μg/mL and 0.26 ± 0.01 μg/mL, respectively). Structure–activity relationship analysis highlighted the crucial role of acetyl and bromo substituents in enhancing enzyme inhibition. These findings position triazole-based scaffolds as promising candidates for the development of next-generation antidiabetic therapies.

Purpose Ti6Al4V alloy has received a great deal of attention in medical applications due to its biomechanical compatibility. However, the human bone stiffness is between 10 and 30 GPa while solid Ti6Al4V is several times stiffer, which would cause stress shielding with the surrounding bone, which can lead to implant and/or the surrounding bone’s failure. Design/methodology/approach In this work, the effect of selective laser melting (SLM) process parameters on the characteristics of Ti6Al4V samples, such as porosity level, surface roughness, elastic modulus and compressive strength (UCS), has been investigated using response surface method. The examined ranges of process parameters were 35-50 W for laser power, 100-400 mm/s for scan speed and 35-120 µm for hatch spacing. The process parameters have been optimized to obtain structures with properties very close to that in human bones. Findings The results showed that the porosity percentage of a SLM component could be increased by reducing the laser power and/or increasing the scan speed and hatch spacing. It was also shown that there was a reverse relationship between the porosity level and both the modulus of elasticity and UCS of the SLM part. In addition, the increased laser power was resulted into a substantial decrease of the surface roughness of SLM parts. Results from the optimization study revealed that the interaction between laser process parameters (i.e. laser power, laser speed, and the laser spacing) have the most significant influence on the mechanical properties of fabricated samples. The optimized values for the manufacturing of medical implants were 49 W, 400 mm/s and 99 µm for the laser power, laser speed and laser spacing, respectively. The corresponding porosity, surface roughness, modulus of elasticity and UCS were 23.62 per cent, 8.68 µm, 30 GPa and 522 MPa, respectively. Originality/value Previous investigations related to additive manufacturing of Ti alloys have focused on producing fully dense and high-integrity structures. There is a clear gap in literature regarding the simultaneous enhancement and adjustment of pore fraction, surface and mechanical properties of Ti6Al4V SLM components toward biomedical implants. This was the objective of the current study.

Over the past 30 years, no consistent survival benefits have been recorded for anticancer agents of advanced hepatocellular carcinoma (HCC), except for the multikinase inhibitor sorafenib (Nexavar ), which clinically achieves only ~3 months overall survival benefit. This modest benefit is attributed to limited aqueous solubility, slow dissolution rate and, consequently, limited absorption from the gastrointestinal tract. Thus, novel formulation modalities are in demand to improve the bioavailability of the drug to attack HCC in a more efficient manner. In the current study, we aimed to design a novel sorafenib-loaded carbon nanotubes (CNTs) formula that is able to improve the therapeutic efficacy of carried cargo against HCC and subsequently investigate the antitumour activity of this formula. Sorafenib was loaded on functionalized CNTs through physical adsorption, and an alginate-based method was subsequently applied to microcapsulate the drug-loaded CNTs (CNTs-SFN). The therapeutic efficacy of the new formula was estimated and compared to that of conventional sorafenib, both in vitro (against HepG2 cells) and in vivo (in a DENA-induced HCC rat model). The in vitro MTT anti-proliferative assay revealed that the drug-loaded CNTs formula was at least two-fold more cytotoxic towards HepG2 cells than was sorafenib itself. Moreover, the in vivo animal experiments proved that our innovative formula was superior to conventional sorafenib at all assessed end points. Circulating AFP-L3% was significantly decreased in the CNTs-SFN-MCs-treated group (14.0%) in comparison to that of the DENA (40.3%) and sorafenib (38.8%) groups. This superiority was further confirmed by Western blot analysis and immunofluorescence assessment of some HCC-relevant biomarkers. Our results firmly suggest the distinctive cancer-suppressive nature of CNTs-SFN-MCs, both against HepG2 cells in vitro and in a DENA-induced HCC rat model in vivo, with a preferential superiority over conventional sorafenib.

Skin is the largest mechanical barrier against invading pathogens. Following skin injury, the healing process immediately starts to regenerate the damaged tissues and to avoid complications that usually include colonization by pathogenic bacteria, leading to fever and sepsis, which further impairs and complicates the healing process. So, there is an urgent need to develop a novel pharmaceutical material that promotes the healing of infected wounds. The present work aimed to prepare and evaluate the efficacy of novel azithromycin-loaded zinc oxide nanoparticles (AZM-ZnONPs) in the treatment of infected wounds. The Box–Behnken design and response surface methodology were used to evaluate loading efficiency and release characteristics of the prepared NPs. The minimum inhibitory concentration (MIC) of the formulations was determined against Staphylococcus aureus and Escherichia coli. Moreover, the anti-bacterial and wound-healing activities of the AZM-loaded ZnONPs impregnated into hydroxyl propyl methylcellulose (HPMC) gel were evaluated in an excisional wound model in rats. The prepared ZnONPs were loaded with AZM by adsorption. The prepared ZnONPs were fully characterized by XRD, EDAX, SEM, TEM, and FT-IR analysis. Particle size distribution for the prepared ZnO and AZM-ZnONPs were determined and found to be 34 and 39 nm, respectively. The mechanism by which AZM adsorbed on the surface of ZnONPs was the best fit by the Freundlich model with a maximum load capacity of 160.4 mg/g. Anti-microbial studies showed that AZM-ZnONPs were more effective than other controls. Using an experimental infection model in rats, AZM-ZnONPs impregnated into HPMC gel enhanced bacterial clearance and epidermal regeneration, and stimulated tissue formation. In conclusion, AZM -loaded ZnONPs are a promising platform for effective and rapid healing of infected wounds.

The antibiotic Ciprofloxacin (CIPRO) was investigated as a new inhibitor for copper corrosion in Synthetic Acid Rain Solution (SAR) utilizing Mass Loss (ML) as a chemical method, Potentiodynamic Polarization (PDP), and Electrochemical Impedance Spectroscopy (EIS) as electrochemical techniques. In the presence of 600 ppm of the antibiotic CIPRO, the protection percentage reached 90.1% according to the EIS technique. Thermodynamic adsorption and activation characteristics were evaluated and described. The CIPRO adsorption on the Cu surface in the SAR solution was physical adsorption and complied with the Langmuir isotherm. According to PDP curves, the studied medication was served as a mixed type of inhibitor. This medication prevented corrosion by adhering to the metallic surface, which was demonstrated by Atomic Force Microscopy (AFM), Scanning Electron Microscopy-Energy Dispersive X-Ray (SEM–EDX), and Fourier-Transform Infrared Spectroscopy (FTIR). Results from the Density Functional Theory (DFT) and Monte Carlo simulations (MC) complement experimental results. The inhibition efficiencies obtained via different methods are consistent with each other. Graphical Abstract

Hyperlipidemia is still the leading cause of heart disease in patients with hypertension. The purpose of this study is to make rosuvastatin calcium (ROS) and atenolol (AT) bilayer tablets to treat coexisting dyslipidemia and hypertension with a single product. ROS was chosen for the immediate-release layer of the constructed tablets, whereas AT was chosen for the sustained-release layer. The solid dispersion of ROS with sorbitol (1:3 w/w) was utilized in the immediate-release layer while hydroxypropyl methylcellulose (HPMC), ethylcellulose (EC), and sodium bicarbonate were incorporated into the floating sustained-release layer. The concentrations of HPMC and EC were optimized by employing 32 full factorial designs to sustain AT release. The bilayer tablets were prepared by the direct compression method. The immediate-release layer revealed that 92.34 ± 2.27% of ROS was released within 60 min at a pH of 1.2. The second sustained-release layer of the bilayer tablets exhibited delayed release of AT (96.65 ± 3.36% within 12 h) under the same conditions. The release of ROS and AT from the prepared tablets was found to obey the non-Fickian diffusion and mixed models (zero-order, Higuchi and Korsmeyer–Peppas), respectively. Preclinical studies using rabbit models investigated the impact of ROS/AT tablets on lipid profiles and blood pressure. A high-fat diet was used to induce obesity in rabbits. Bilayer ROS/AT tablets had a remarkable effect on decreasing the lipid profiles, slowing weight gain, and lowering blood pressure to normal levels when compared to the control group.

Luteolin (LUT) is a natural flavonoid with low oral bioavailability with restricted clinical applications due to its low solubility. LUT shows significant anti-tumor activity in many cancer cells, including hepatocellular carcinoma (HCC). The most recent trend in pharmaceutical innovations is the application of phospholipid vesicles to improve the solubility of such hydrophobic drugs. Ethosomes are one of the most powerful phospholipid vesicles used to achieve that that target. In this study, LUT-loaded ethosomal nanoparticles (LUT-ENPs) were prepared by the cold method. Full factorial design and response surface methodology were used to analyze and optimize the selected formulation variables. Drug entrapment efficiency, vesicle size, zeta potential, Fourier transform infra-red spectroscopy, scanning electron microscopy, and cumulative percent drug released was estimated. The selected LUT-ENPs were subjected to further investigations as estimation of hepatic gene expression levels of GPC3, liver biomarkers, and oxidative stress biomarkers. The prepared LUT-ENPs were semi-spherical in shape with high entrapment efficiency. The prepared LUT-ENPs have a small particle size with high zeta potential values. The in vitro liver biomarkers assay revealed a significant decrease in the hepatic tissue nitric oxide (NO), malondialdehyde (MDA) content, and the expression of the GPC3 gene. Results showed a high increase in the hepatic tissue levels of glutathione (GSH) and superoxide dismutase (SOD). Histopathological examination showed a small number of hepatic adenomas and a significant decrease of neoplastic hepatic lesions after treatment with LUT-ENPs. Our results firmly suggest the distinctive anti-proliferative activity of LUT-ENPs as an oral drug delivery system for the treatment of HCC.

Microwave pyrolysis of corn stover has been optimized by Response surface methodology under different microwave power (500, 700, and 900 W) and three ratios of activated carbon additive (10, 15, and 20%) for obtaining maximum bio-oil yield followed by biochar. The optimal result has been evaluated and the environmental and techno-economic impacts of using solar-powered microwave heating have been tested. The optimal pyrolysis condition found to be 700 W microwave power and 10% of activated carbon. The yields of both bio-oil and biochar were about 74 wt% under optimal condition. The higher heat values of 26 MJ/kg and 16 MJ/kg were respectively achieved for biochar and bio-oil. The major components of bio-oil were hydrocarbons (36%) and phenols (28%) with low oxygen-containing compounds (2%) and acids (2%). Using the solar-powered system, 20,549 tonnes of CO 2 can be mitigated over the lifetime of the set-up, resulting in USD 51,373 in carbon credit earnings, compared to 16,875 tonnes of CO 2 mitigation and USD 42,167 in carbon credit earnings from a grid electricity system. The payback periods for solar-powered and grid-connected electrical systems are estimated to be 1.6 and 0.5 years, respectively, based on biochar and bio-oil income of USD 39,700 and USD 45,400.

The current study offers a metal-free, direct, and successful synthesis technique for a new series of quinolinone and benzo[d][1,3]oxazine, along with an assessment of their biological activities. Heteroannulation of anthranilic acid with carbonyl-containing chemicals (aroyl pyruvate, ethyl acetoacetatete, maleic anhydride, and ethyl cyanoacetate) resulted in the desired quinolones and benzo[d][1,3]oxazines. This technique introduces a number of fundamental breakthroughs in organic synthesis, including metal-free catalysts, smart reaction conditions with column purification, and a wide functional scope. Furthermore, the structure of the newly synthesized chemical series was investigated and validated using spectroscopic techniques. The synthesized series were evaluated for antibacterial (against gram-positive and gram-negative bacterial strains) and antifungal activity. The quinolone and benzo[d][1,3]oxazine candidates had remarkable antibacterial action. Furthermore, molecular docking investigations corroborated the biological studies using the Molecular Operating Environment and Petro Osiris Molinspiration (POM) experiments, which confirmed the activity of compounds 8 , 15 , and 17 . Our studies on the cytotoxic activity of various chemicals have demonstrated that these compounds exhibit minimal toxicity. Specifically, when comparing the cytotoxic effects on human lung fibroblast (WI38) cells to those of Doxorubicin , a well-known chemotherapy agent, compounds 8 , 15 , and 17 showed weak cytotoxic effects on the normal WI38 cells. This indicates that these compounds may possess some level of selectivity and reduced toxicity towards normal cells, suggesting potential for further exploration as antibacterial agents with a safer profile for normal cells.

Gefitinib (GFT) is a tyrosine kinase inhibitor drug used as a first-line treatment for patients with advanced or metastatic non-small cell lung, colon, and breast cancer. GFT exhibits low solubility and hence low oral bioavailability, which restricts its clinical application. One of the most important trends in overcoming such problems is the use of a vesicular system. Cubosomes are considered one of the most important vesicular systems used to improve solubility and oral bioavailability. In this study, GFT cubosomal nanoparticles (GFT-CNPs) were prepared by the emulsification method. The selected formulation variables were analyzed and optimized by full factorial design and response surface methodology. Drug entrapment efficiency (EE%), transmission electron microscopy, particle size, polydispersity index, in vitro release and its kinetics, and the effect of storage studies were estimated. The chosen GFT-CNPs were subjected to further investigations as gene expression levels of tissue inhibitors of metalloproteinases-1 (TIMP-1) and matrix metalloproteinases-7 (MMP-7), colon biomarkers, and histopathological examination of colon tissues. The prepared GFT-CNPs were semi-cubic in shape, with high EE%, smaller vesicle size, and higher zeta potential values. The in vivo data showed a significant decrease in the serum level of embryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9), and gene expression level of TIMP-1 and MMP-7. Histopathological examination showed enhancement in cancer tissue and highly decreased focal infiltration in the lamina propria after treatment with GFT-CNPs.