Correction to "Ion-Exchange Resin/Carrageenan-Copper-Based Nanocomposite: Artificial Neural Network, Advanced Thermodynamic Profiling, and Anticoagulant Studies".

[This corrects the article DOI: 10.1021/acsomega.4c01540.].

Development of Polymeric Micelles for Combined Delivery of Luteolin and Doxorubicin for Cancer Therapy.

Background: Luteolin (LUT) is a bioactive compound with several pharmacological activities including anticancer effect. Doxorubicin (DOX) is an anthracycline chemotherapeutic drug that have proven to be effective in treating various types of cancers. Polymeric micelles (PMs) containing biologically active materials have emerged as prospective dosage forms with high drug-loading, which can add therapeutic benefit to the poorly water-soluble compounds and novel chemical entities. PMs are effective in delivering several drugs, such as anticancer drugs, antifungal drugs, flavonoids and drugs targeting the brain. The aim of the current study is to develop PMs for LUT and DOX as a combined delivery system for cancer therapy. Methods: PMs were prepared using 2.5% of each of LUT and DOX with varying compositions of Poloxamer 188, Poloxamer 407, Vitamin E (TPGS), Poloxamer 123 and Gellucire 44/14 at room temperature. Particle size, polydispersity index, zeta potential, were achieved using Zetasizer Nano particle size analyzer and the sizes were further confirmed with transmission electron microscopy (TEM). Prepared PMs were further characterized using powder X-ray diffraction (PXRD) and fourier transform infrared spectroscopy (FTIR). An MTT assay was performed on breast cancer (MCF-7) cells and liver cancer (HepG2) cells to determine the cytotoxic effect of the different PMs formulations. Results: PMs were successfully developed and optimized using 74.3% Poloxamer 407 with 20.7% Vitamin E (TPGS), and 70% Poloxamer 407 with 25% Gellucire 44/14, respectively. The droplet size and polydispersity index were found to be 62.03 ± 3.99 nm, 91.96 ± 5.80 nm and 0.33 ± 0.05, 0.59± 0.03, respectively for PMs containing TPGS and Gellucire 44/14. Zeta potentials of the PMs containing TPGS and Gellucire 44/14 were recorded as -2.27 ±0.11mV and -7.78 ± 0.10 mV, respectively. The PMs showed a spherical structure with approximately 50-90 nm range evident by TEM analysis. The PXRD spectra of PMs powder presented the amorphization of LUT and DOX. The FTIR spectra of LUT-loaded and DOX-loaded PMs were identical, suggesting consistent PMs composition. The MTT assay showed that the representative combined drug loaded PMs treatment led to a reduction in the viability of MCF-7 and HepG2 cells compared to drug free PMs and pure LUT, DOX alone. Conclusions: PMs with LUT and DOX exhibited significant cytotoxic effects against breast and liver cancer cells and could thus be an important new pharmaceutical formulation to treat cancer.

pH-Sensitive Hydrogels Fabricated with Hyaluronic Acid as a Polymer for Site-Specific Delivery of Mesalamine.

Hydrogels with the main objective of releasing mesalamine (5-aminosalicylic acid) in the colon in a modified manner were formulated in the present work using a free-radical polymerization approach. Different ratios of hyaluronic acid were cross-linked with methacrylic and acrylic acids using methylenebis(acrylamide). The development of a new polymeric network and the successful loading of drug were revealed by Fourier transform infrared spectroscopy. Thermogravimetric analysis demonstrated that the hydrogel was more thermally stable than the pure polymer and drug. Scanning electron microscopy (SEM) revealed a rough and hard surface which was relatively suitable for efficient loading of drug and significant penetration of dissolution medium inside the polymeric system. Studies on swelling and drug release were conducted at 37 °C in acidic and basic conditions (pH 1.2, 4.5, 6.8, and 7.4, respectively). Significant swelling and drug release occurred at pH 7.4. Swelling, drug loading, drug release, and gel fraction of the hydrogels increased with increasing hyaluronic acid, methacrylic acid, and acrylic acid concentrations, while the sol fraction decreased. Results obtained from the toxicity study proved the formulated system to be safe for biological systems. The pH-sensitive hydrogels have the potential to be beneficial for colon targeting due to their pH sensitivity and biodegradability. Inflammatory bowel disease may respond better to hydrogel treatment as compared to conventional dosage forms. Specific amount of drug is released from hydrogels at specific intervals to maintain its therapeutic concentration at the required level.

Black Seed Oil-Based Curcumin Nanoformulations Ameliorated Cuprizone-Induced Demyelination in the Mouse Hippocampus.

Multiple sclerosis (MS) is a neurodegenerative disease characterized by the demyelination of nerves, axonal damage, and neuroinflammation. Cognition impairment, pain, and loss of mobility are some of the usual complications of MS. It has been postulated that the overproduction of proinflammatory cytokines and reactive oxygen species (ROS) are the main factors that contribute to MS pathology. Among various animal models, the cuprizone model is the most widely used model for investigating MS-related pathology. We assessed the effects of cuprizone along with the protective effects of some black seed oil-based nanoformulations of curcumin with and without piperine, in mice hippocampus in terms of the changes in antioxidant enzymes, transcription factors, and cytokines during demyelination and remyelination processes. The results of behavioral studies point toward impairment in working memory following the feeding of cuprizone for 5 weeks. However, in treatment groups, mice seemed to prevent the toxic effects of cuprizone. Nanoformulations used in this study were found to be highly effective in lowering the amount of ROS as indicated by the levels of antioxidant enzymes like catalase, superoxide dismutase, glutathione, and glutathione peroxidase. Moreover, nanoformulations CCF and CCPF were observed resisting the toxic effects of cuprizone. We observed greater expression of NFκB-p65 in the CPZ group than in the control group. CCF nanoformulation had a better inhibitory effect on NFκB-p65 than other formulations. Histological examination of the hippocampus was also conducted. Nanoformulations used here were found effective in reversing MS-related pathophysiology and hence have the potential to be applied as adjuvant therapy for MS treatment.

Ion-Exchange Resin/Carrageenan-Copper-Based Nanocomposite: Artificial Neural Network, Advanced Thermodynamic Profiling, and Anticoagulant Studies.

Carrageenan (CG) and ion exchange resins (IERs) are better metal chelators. Kappa (κ) CG and IERs were synthesized and subjected to copper ion (Cu2+) adsorption to obtain DMSCH/κ-Cu, DC20H/κ-Cu, and IRP69H/κ-Cu nanocomposites (NCs). The NCs were studied using statistical physics formalism (SPF) at 315-375 K and a multilayer perceptron with five input nodes. The percentage of Cu2+ uptake efficiency was used as an outcome variable. Via the grand canonical ensemble, SPF gives models for both monolayer and multilayer sorption layers. For in vitro anticoagulant activity (ACA), the activated partial thromboplastin time were calculated using 100 µL of rabbit plasma incubated at 37 °C. After 2 min, 100 L of 0.025 M CaCl2 was added, and the clotting time was recorded for each group (n = 6). The results demonstrated that the key covariables for the adsorption process were pH and concentration. The results of artificial neural network models were comparable with the experimental findings. The error rates varied between 4.3 and 1.0%. The prediction analysis results ranged from 43.6 to 89.2. The ΔG and ΔS values for IRP69H/κ-Cu obtained were -18.91 and -16.32 and 26.21 and 22.74 kJ/mol for the temperatures 315 and 345 K, respectively. Adsorbate species were perpendicular to the adsorbent surfaces, notwithstanding the apparent importance of macro- and micropore volumes. These adsorbents typically fluctuate with temperature changes and contain one or more layers of sorption. Negative and positive sorption energies correspond to endothermic and exothermic processes. The biosorption energy (E1 and E2) values in this experiment have a value of less than 23 kJ mol-1. Complex SPF models' energy distributions validate surface properties and interactions with adsorbates. At a concentration of 100 µg/mL, DC20H/κ-Cu2+ exhibited an ACA of only 8 s. These NCs demonstrated better greater ACA with the order DC20H/κ < DMSCH/κ < IRP69H/κ. More research is needed to rule out the chemical processes behind the ACA of CG/IER-Cu NCs.

Efficient Synthesis of Mannopyranoside-based Fatty Acyl Esters: Effects of Acyl Groups on Antimicrobial Potential.

BACKGROUND: The approval of Sucrose Fatty Acid Esters (SFAEs) as food additives/ preservatives with antimicrobial potential has triggered enormous interest in discovering new biological applications. Accordingly, many researchers reported that SFAEs consist of various sugar moieties, and hydrophobic side chains are highly active against certain fungal species. OBJECTIVE: This study aimed to conduct aregioselective synthesis of SAFE and check the effect of chain length and site of acylation (i.e., C-6 vs. C-2, C-3, C-4, and long-chain vs. short-chain) on antimicrobial potency. METHODS: A direct acylation method maintaining several conditions was used for esterification. In vitro tests, molecular docking, and in silico studies were conducted using standard procedures. RESULTS: In vitro tests revealed that the fatty acid chain length in mannopyranoside esters significantly affects the antifungal activity, where C12 chains are more potent against Aspergillus species. In terms of acylation site, mannopyranoside esters with a C8 chain substituted at the C-6 position are more active in antifungal inhibition. Molecular docking also revealed that these mannopyranoside esters had comparatively better stable binding energy and hence better inhibition, with the fungal enzymes lanosterol 14-alpha-demethylase (3LD6), urate oxidase (1R51), and glucoamylase (1KUL) than the standard antifungal drug fluconazole. Additionally, the thermodynamic, orbital, drug-likeness, and safety profiles of these mannopyranoside esters were calculated and discussed, along with the Structure-Activity Relationships (SAR). CONCLUSION: This study thus highlights the importance of the acylation site and lipid-like fatty acid chain length that govern the antimicrobial activity of mannopyranoside-based SFAE.

Rosmanol Triggers Apoptosis Against MNNG-induced Gastric Carcinogenesis in Rats through Attenuation of the P13K/AKT/HMBG1 Signaling Pathway.

BACKGROUND: Gastric cancer (GC) is a frequent malignant neoplasm found in China. Despite numerous therapeutic methodologies to ameliorate the well-being of GC patients, their efficiency remains inadequate. OBJECTIVE: Rosmanol (RML) is a phenolic diterpene compound with antioxidant and anticancer activities. In the current research, the apoptotic efficacy of RML on methylnitronitrosoguanidine (MNNG)-induced GC model was determined. MATERIALS AND METHODS: The rats were allocated into four sets, viz., normal control, MNNG (200 mg/kg bw) + NaCl, MNNG + RML (20 mg/kg), and RML (20 mg/kg) orally treated for 20 weeks. RESULTS: The results exposed that GC rats revealed higher (P<0.05) levels of TBARS and reduced antioxidant status in the stomach and liver tissues counter to other groups. In contrast, the TBARS level was substantially alleviated (P<0.05) and restored the antioxidant status in RMLadministered rats. Histopathologic assessment of gastric tissue unveiled that an MNNG-induced group presented squamous cell carcinoma with keratin pearls. The administration of RML reduced GC incidence, and only mild dysplasia was observed. Further, RML alleviated Bcl-2, P13K, AKT, and HMGB1, as evidenced by RT-PCR and Western blot analysis. CONCLUSION: Furthermore, RML triggered caspase-mediated mitochondrial apoptosis through the inactivation of the PI3K/AKT/HMGB1 pathway, eventually leading to GC cell death. This highlights that RML may be a potential natural antioxidant employed as a chemoprotective agent in GC rats.

Analyzing molecular signatures in preeclampsia and fetal growth restriction: Identifying key genes, pathways, and therapeutic targets for preterm birth.

Background: Intrauterine growth restriction (IUGR) and preeclampsia (PE) are intricately linked with specific maternal health conditions, exhibit shared placental abnormalities, and play pivotal roles in precipitating preterm birth (PTB) incidences. However, the molecular mechanism underlying the association between PE and IUGR has not been determined. Therefore, we aimed to analyze the data of females with PE and those with PE + IUGR to identify the key gene(s), their molecular pathways, and potential therapeutic interactions. Methods: In this study, a comprehensive relationship analysis of both PE and PE + IUGR was conducted using RNA sequence datasets. Using two datasets (GSE148241 and GSE114691), differential gene expression analysis via DESeq2 through R-programming was performed. Gene set enrichment analysis was performed using ClusterProfiler, protein‒protein interaction (PPI) networks were constructed, and cluster analyses were conducted using String and MCODE in Cytoscape. Functional enrichment analyses of the resulting subnetworks were performed using ClueGO software. The hub genes were identified under both conditions using the CytoHubba method. Finally, the most common hub protein was docked against a library of bioactive flavonoids and PTB drugs using the PyRx AutoDock tool, followed by molecular dynamic (MD) simulation analysis. Pharmacokinetic analysis was performed to determine the ADMET properties of the compounds using pkCSM. Results: We identified eight hub genes highly expressed in the case of PE, namely, PTGS2, ENG, KIT, MME, CGA, GAPDH, GPX3, and P4HA1, and the network of the PE + IUGR gene set demonstrated that nine hub genes were overexpressed, namely, PTGS2, FGF7, FGF10, IL10, SPP1, MPO, THBS1, CYBB, and PF4. PTGS2 was the most common hub gene found under both conditions (PE and PEIUGR). Moreover, the greater (-9.1 kcal/mol) molecular binding of flavoxate to PTGS2 was found to have satisfactory pharmacokinetic properties compared with those of other compounds. The flavoxate-bound PTGS2 protein complex remained stable throughout the simulation; with a ligand fit to protein, i.e., a RMSD ranging from ∼2.0 to 4.0 Å and a RMSF ranging from ∼0.5 to 2.9 Å, was observed throughout the 100 ns analysis. Conclusion: The findings of this study may be useful for treating PE and IUGR in the management of PTB.

Chitosan-PVA-PVP/nano-clay composite: a promising tool for controlled drug delivery.

In this study, chitosan, polyvinyl alcohol (PVA), and polyvinyl pyrrolidone (PVP) were used to create ternary blends reinforced with organically modified montmorillonite nanoclay. Tramadol was used as a model drug to assess the efficacy of these ternary blends as drug delivery systems. The current work demonstrated the highly controlled release of tramadol via transdermal administration. The results of the FTIR investigation revealed the compatibility of the blending components. Among non-drug-loaded formulations, MC6 is the most stable with a 17.6% weight residue at 505 °C and MC11 is the most stable of all the drug-loaded and non-drug-loaded formulations with a weight residue of 22.0% at 505 °C. The XRD studies of the prepared formulations showed crystalline behavior. However, the SEM analysis revealed that no gaps or mixing components were uniformly dispersed in the nanocomposites. Pharmaceutical tests, such as swelling, dissolution, and permeation rates, revealed a strong influence of the PVA concentration. There was a uniform distribution of drug throughout the films with maximum encapsulation efficiency found for MC7 (96.09 ± 0.31) and minimum encapsulation efficiency for MC11 (90.56 ± 0.34)%. Compared to the sodium acetate (pH 4.5) and potassium phosphate buffers (pH 6.8) the swelling and erosion were higher in hydrochloric acid buffer (pH 1.2). An increase in PVA concentration (or decrease in PVP concentration) increases the swelling, dissolution, and permeation rates. In addition, erosion increased with increasing PVP concentration. Furthermore, the nanoclay-reinforced composite showed high permeation. Based on the obtained results, it can be concluded that the produced nanocomposite could be used as an efficient transdermal drug delivery system.

Exploring Zingiber officinale bioactive compounds for inhibitory effects on Streptococcus pneumoniae capsular polysaccharide biosynthesis proteins: In silico study.

The capsule is a major virulence factor for Streptococcus pneumoniae which causes global morbidity and mortality. It is already known that there are few conserved genes in the capsular biosynthesis pathway, which are common among all known serotypes, called CpsA, CpsB, CpsC and CpsD. Inhibiting capsular synthesis can render S. pneumoniae defenseless and vulnerable to phagocytosis. The Inhibitory potential of active Zingiber officinale compounds was investigated against the 3D (3-dimensional) structural products of Cps genes using in silico techniques. A 3D compound repository was created and screened for drug-likeness and the qualified compounds were used for molecular docking and dynamic simulation-based experiments using gallic acid for outcome comparison. Cavity-based docking revealed five different cavities in the CpsA, CpsB and CpsD proteins, with gallic acid and selected compounds of Zingiber in a binding affinity range of -6.8 to -8.8 kcal/mol. Gingerenone A, gingerenone B, isogingerenone B and gingerenone C showed the highest binding affinities for CpsA, CpsB and CpsD, respectively. Through the Molegro Virtual Docker re-docking strategy, the highest binding energies (-126.5 kcal/mol) were computed for CpsB with gingerenone A and CpsD with gingerenone B. These findings suggest that gingerenone A, B and C are potential inhibitors of S. pneumoniae-conserved capsule-synthesizing proteins.

Structural elucidation and development of azelaic acid loaded mesoporous silica nanoparticles infused gel: Revolutionizing nanodrug delivery for cosmetics and pharmaceuticals.

This research aimed to enhance dermal delivery and optimize depigmentation therapy by designing mesoporous silica nanoparticles (MSNs) encapsulating azelaic acid (AZA) within a gel matrix. The MSNs were prepared using the sol-gel method. After subsequent processes, including acid extraction and drug loading, were then elucidated through PDI, size, zeta-potential, entrapment efficiency, nitrogen adsorption assay, FE-SEM, thermogravimetric analysis, differential scanning calorimetry, Fourier transform infrared spectroscopy, X-ray diffraction, and tyrosinase inhibition assay, were employed to assess the formulation. In-vitro stability tests for both AZA-MSN gel (AZCG) and AZA-loaded mesoporous silica gel (AZMG) were conducted at 8 °C, 25 °C, 40 °C, and 40 °C + 75 % RH, encompassing assessments of color, liquefaction, pH, and conductivity. Our findings showed a notable entrapment efficiency of 93.46 % for AZA-MSNs, with FE-SEM illustrating porous spherical MSNs. The particle size of AZA-MSNs was determined to be 211.9 nm, with a pore size of 2.47 nm and XRD analysis confirmed the amorphous state of AZA within the MSN carriers. Rheology examination indicated a non-Newtonian flow, while ex-vivo rat skin permeation studies conducted in a phosphate buffer (pH = 5.5) demonstrated a biphasic release pattern with 85.53 % cumulative drug permeation for AZA-MSNs. Overall, the study endorse the potential of AZA-MSNs as an efficacious and stable formulation for AZA delivery, highlighting their promise in addressing pigmentation concerns compared to conventional approaches.

Assessment of coastal river water quality in Bangladesh: Implications for drinking and irrigation purposes.

Saltwater intrusion in the coastal areas of Bangladesh is a prevalent phenomenon. However, it is not conducive to activities such as irrigation, navigation, fish spawning and shelter, and industrial usage. The present study analyzed 45 water samples collected from 15 locations in coastal areas during three seasons: monsoon, pre-monsoon, and post-monsoon. The aim was to comprehend the seasonal variation in physicochemical parameters, including water temperature, pH, electrical conductivity (EC), salinity, total dissolved solids (TDS), hardness, and concentrations of Na+, K+, Mg2+, Ca2+, Fe2+, HCO3-, PO43-, SO42-, and Cl-. Additionally, parameters essential for agriculture, such as soluble sodium percentage (SSP), sodium absorption ratio (SAR), magnesium absorption ratio (MAR), residual sodium carbonate (RSC), Kelly's ratio (KR), and permeability index (PI), were examined. Their respective values were found to be 63%, 16.83 mg/L, 34.92 mg/L, 145.44 mg/L, 1.28 mg/L, and 89.29%. The integrated water quality index was determined using entropy theory and principal component analysis (PCA). The resulting entropy water quality index (EWQI) and SAR of 49.56% and 63%, respectively, indicated that the samples are suitable for drinking but unsuitable for irrigation. These findings can assist policymakers in implementing the Bangladesh Deltaplan-2100, focusing on sustainable land management, fish cultivation, agricultural production, environmental preservation, water resource management, and environmental protection in the deltaic areas of Bangladesh. This research contributes to a deeper understanding of seasonal variations in the hydrochemistry and water quality of coastal rivers, aiding in the comprehension of salinity intrusion origins, mechanisms, and causes.

Herbal Spices as Food and Medicine: Microscopic Authentication of Commercial Herbal Spices.

Herbal spices are an agricultural commodity, economically very important and beneficial in primary healthcare in the food and medicine sectors. Herbal spices are used as food flavoring agents as well as in phytotherapies throughout the world and have nutritive benefits. The food and medicine industries widely employ artificial or natural adulteration to retard the deterioration and utilization of these adulterants in food and medicine products has given rise to significant apprehension among consumers, primarily stemming from the potential health risks that they pose. Thus, their characterization for the purpose of identification, origin, and quality assurance is mandatory for safe human consumption. Here, we studied 22 samples of commonly traded herbal spices that belong to 20 different genera and 21 species comprising 14 families, investigated macroscopically or organoleptically as well as histologically under microscopic examination. In this study, we provide details on organoleptic features including appearance, taste, odor, color, shape, size, fractures, types of trichomes, and the presence of lenticels among the examined herbal spices and these features have great significance in the detection of both natural as well as artificial deterioration. In terms of microscopic characterization, each examined plant part comprising different anatomical characteristics has taxonomic importance and also provides useful information for authentication from natural adulterants. Furthermore, the studied taxa were also described with nutritive and therapeutic properties. For condiments, herbal beverages and medicinal purposes, different herbal parts such as leaves, floral buds, seeds, fruit, and accessory parts like mericarp, rhizome, bulbs, and bark were used and commercially traded. Similarly, in this study, the leaves of Cinnamomum tamala and Mentha spicata, the floral buds of Syzygium aromaticum, the seeds of Amomum subulatum, Brassica nigra, Punica granatum, Myristica fragrans, Phyllanthus emblica, and Elettaria cardamomum, the mericarp of Coriandrum sativum, and Cuminum cyminum were observed. As a result, we show the potential of herbal spices as a source of many valuable phytochemicals and essential nutrients for food, nutraceutical, and homoeopathic medicine.

Evolution of structural and electronic properties standardized description in rhenium disulfide at the bulk-monolayer transition.

The structural and electronic properties of ReS2 different forms - three-dimensional bulk and two-dimensional monolayer - were studied within density functional theory and pseudopotentials. A method for standardizing the description of bulk unit cells and "artificial" slab unit cells for DFT research has been proposed. The preference of this method for studying zone dispersion has been shown. The influence of the vacuum layer thickness on specified special high-symmetry points is discussed. Electron band dispersion in both classical 3D Brillouin zones and transition to 2D Brillouin zones in the proposed two-dimensional approach using the Niggli form of the unit cell was compared. The proposed two-dimensional approach is preferable for low-symmetry layered crystals such as ReS2. It was established that the bulk ReS2 is a direct gap semiconductor (band gap of 1.20 eV), with the direct transition lying in the X point of the first Brillouin zone, and it is in good agreement with published experimental data. The reduction in material dimension from bulk to monolayer was conducted with an increasing band gap up to 1.45 eV, with a moving direct transition towards the Brillouin zone center. The monolayer of ReS2 is a direct-gap semiconductor in a wide range of temperatures, excluding only a narrow range at low temperatures, where it comes as a quasi-direct gap semiconductor. The transition, situated directly in the Γ-point, lies 3.3 meV below the first direct transition located near this point. The electronic density of states of ReS2 in the bulk and monolayer cases of ReS2 were analyzed. The molecular orbitals were built for both types of ReS2 structures as well as the electron difference density maps. For all types of ReS2 structures, an analysis of populations according to Mulliken and Voronoi was carried out. All calculated data is discussed in the context of weak quantum confinement in the 2D case.

Nutraceutically-enhanced oral delivery of vitamin D3 via Bio-SNEDDS: Demonstrating in vivo superiority over pediatric formulations.

BACKGROUND: Vitamin D3 (VD3) deficiency among children in Saudi Arabia remains a pressing concern due to its poor bioavailability and the limitations of current pediatric formulations. To address this challenge, we developed a groundbreaking pediatric self-nanoemulsifying drug delivery system (Bio-SNEDDS) for VD3, fortified with black seed oil and moringa seed oil for dual therapeutic benefits. Through meticulous formulation optimization using ternary phase diagrams and comprehensive testing, our Bio-SNEDDS demonstrated exceptional performance. METHODS: Bio-SNEDDS were manufactured by incorporating Black seed oil and moringa seed oil as bioactive nutraceutical excipients along with various cosurfactant and surfactants. Bio-SNEDDS were systematically optimized through ternary phase diagrams, visual tests, droplet size analysis, drug solubilization studies, dispersion assessments, and pharmacokinetic testing in rats compared to Vi-De 3®. RESULTS: Pseudoternary phase diagrams identified oil blends producing large nanoemulsion regions optimal for SNEDDS formation. The optimized F1 Bio-SNEDDS showed a mean droplet diameter of 33.7 nm, solubilized 154.46 mg/g VD3 with no metabolite formation, and maintained >88% VD3 in solution during 24 h dispersion testing. Notably, in vivo pharmacokinetic evaluation at a high VD3 dose demonstrated an approximately two-fold greater relative bioavailability over Vi-De 3®, validating the superb oral delivery performance of Bio-SNEDDS even under challenging high-dose conditions. CONCLUSIONS: The Bio-SNEDDS provides an effective VD3 delivery strategy with established in vivo superiority over marketed products, along with offering additional health benefits from the natural oils.

A NiO-nanostructure-based electrochemical sensor functionalized with supramolecular structures for the ultra-sensitive detection of the endocrine disruptor bisphenol S in an aquatic environment.

Herein, NiO nanoparticles (NPs) functionalized with a para-hexanitrocalix[6]arene derivative (p-HNC6/NiO) were synthesized by using a facile method and applied as a selective electrochemical sensor for the determination of bisphenol S (BPS) in real samples. Moreover, the functional interactions, phase purities, surface morphologies and elemental compositions of the synthesized p-HNC6/NiO NPs were investigated via advanced analytical tools, such as Fourier-transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and energy dispersive X-ray spectroscopy (EDX). Additionally, the synthesized p-HNC6/NiO NPs were cast on the surface of a bare glassy carbon electrode (GCE) via a drop casting method, which resulted in uniform deposition of p-HNC6/NiO/GCE over the surface of the GCE. Additionally, the developed p-HNC6/NiO/GCE sensor demonstrated an outstanding electrochemical response to BPS under optimized conditions, including a supporting electrolyte, a Briton-Robinson buffer electrolyte at pH 4, a scan rate of 110 mV s-1 and a potential window of between -0.2 and 1.0 V. The wide linear dynamic range was optimized to 0.8-70 µM to obtain a brilliant linear calibration curve for BPS. The limit of detection (LOD) and limit of quantification (LOQ) of the developed sensor were estimated to be 0.0059 and 0.019 µM, respectively, which are lower than those of reported sensors for BPS. The feasibility of the developed method was successfully assessed by analyzing the content of BPS in waste water samples, and good recoveries were achieved.

RETRACTED: Khan et al. Poly (N-vinylcaprolactam-grafted-sodium alginate) Based Injectable pH/Thermo Responsive In Situ Forming Depot Hydrogels for Prolonged Controlled Anticancer Drug Delivery; In Vitro, In Vivo Characterization and Toxicity Evaluation. Pharmaceutics 2022, 14, 1050.

The journal retracts the article, "Poly (N-vinylcaprolactam-grafted-sodium alginate) Based Injectable pH/Thermo Responsive In Situ Forming Depot Hy-drogels for Prolonged Controlled Anticancer Drug Delivery; In Vitro, In Vivo Characterization and Toxicity Evaluation" [...].

Exploring the therapeutic potential of edible vegetables, fruits, and spices against cancer in various cell lines.

Cancer is rapidly becoming the leading cause of death globally. This study aimed to identify edible foods with cytotoxic and/or antioxidant activities that can prevent cancer when consumed in a regular diet. Sixty-eight edible foods were purchased from the local market, and the materials were extracted with 80% methanol. The cytotoxic activity of the extracts was evaluated using MTT on HeLa, H2228, HEK293, and H3122 cell lines. To study apoptosis, triple fluorescence labeling with DAPI, Annexin V, and propidium iodide was used. The phenolic content, antioxidant capacity, and free radical scavenging capabilities were studied using conventional spectrophotometric techniques. Among the edible foods, carrot, pointed gourd, wax gourd, ficus, apple, lemon, cumin seed, and white peppercorn showed moderate cytotoxicity in HeLa cells. The growth of HeLa cells was significantly inhibited dose-dependently by tomato, banana, Indian spinach, guava, lemon peel, and coriander (IC50, 24.54, 17.89, 13.18, 9.33, 1.23, and 2.96 µg/mL, respectively). Tomato, Indian spinach, lemon peel, and coriander exerted significant dose-dependent inhibition of H2228, HEK293, and H3122 cell proliferation. The tomato, Indian spinach, lemon peel, and coriander extracts induced HeLa cell apoptosis. White peppercorn, amaranth, apple, wax gourd, cumin seed, taro, and lemon peel contained significant amounts of polyphenols and showed high antioxidant activity. White peppercorn, apple, coriander, lemon peel, and ficus significantly scavenged DPPH free radicals (IC50 values of 10.23, 12.02, 13.49, 13.8, and 14.0 µg/mL, respectively). The overall results suggest that the daily intake of these antioxidant-rich cytotoxic foods can prevent or reduce the risk of cancer.

Unveiling the therapeutic potential: Evaluation of anti-inflammatory and antineoplastic activity of Magnolia champaca Linn's stem bark isolate through molecular docking insights.

Magnolia champaca Linn. has traditionally been used for medicinal activity in Asia for treating various chronic diseases as well as a source of food, medicines, and other commodities. Due to the long-used history of this plant, the present study was designed to explore the in vitro, in vivo and in silico anti-inflammatory and antineoplastic properties of the methanolic extract and fractions and the pure compound isolated from the most active chloroform fraction (CHF) of the stem bark of the plant. The isolated compound from the most active CHF was characterized and identified as a glycoside, trans-syringin, through chromatographic and spectroscopic (1H-NMR and 13C-NMR) analyses. In the in vitro anti-inflammatory assay, CHF was most effective in inhibiting inflammation and hemolysis of RBCs by 73.91 ± 1.70% and 75.92 ± 0.14%, respectively, induced by heat and hypotonicity compared to standard acetylsalicylic acid. In the egg albumin denaturation assay, CME and CHF showed the highest inhibition by 56.25 ± 0.82% and 65.82 ± 3.52%, respectively, contrasted with acetylsalicylic acid by 80.14 ± 2.44%. In an in vivo anti-inflammatory assay, statistically significant (p < 0.05) decreases in the parameters of inflammation, such as paw edema, leukocyte migration and vascular permeability, were recorded in a dose-dependent manner in the treated groups. In the antineoplastic assay, 45.26 ± 2.24% and 68.31 ± 3.26% inhibition of tumor cell growth for pure compound were observed compared to 73.26 ± 3.41% for standard vincristine. Apoptotic morphologic alterations, such as membrane and nuclear condensation and fragmentation, were also found in EAC cells after treatment with the isolated bioactive pure compound. Such treatment also reversed the increased WBC count and decreased RBC count to normal values compared to the untreated EAC cell-bearing mice and the standard vincristine-treated mice. Subsequently, in silico molecular docking studies substantiated the current findings, and the isolated pure compound and standard vincristine exhibited -6.4 kcal/mol and -7.3 kcal/mol binding affinities with topoisomerase-II. Additionally, isolated pure compound and standard diclofenac showed -8.2 kcal/mol and -7.6 kcal/mol binding affinities with the COX-2 enzyme, respectively. The analysis of this research suggests that the isolated bioactive pure compound possesses moderate to potent anti-inflammatory and antineoplastic activity and justifies the traditional uses of the stem bark of M. champaca. However, further investigations are necessary to analyze its bioactivity, proper mechanism of action and clinical trials for the revelation of new drug formulations.

Apoptosis-inducing anti-proliferative and quantitative phytochemical profiling with in silico study of antioxidant-rich Leea aequata L. leaves.

Natural products have been important parts of traditional medicine since ancient times, with various promising health effects. Leea aequata (L. aequata), a natural product, has been widely used for treating several diseases due to its promising pharmacological activities. Therefore, the present study aimed to explore the phytochemical profiling and molecular docking of the antioxidant-rich part of L. aequata leaves and its antiproliferative activity. L. aequata leaves were extracted with methanol, followed by fractionation with the respective solvents to obtain the petroleum ether, chloroform, ethyl acetate, and aqueous fractions. The antioxidant activity was evaluated by spectrophotometric methods. The cytotoxic and antiproliferative activities were detected using MTT colorimetric and confocal microscopy methods, respectively. Phytochemical compositions were analyzed using gas chromatography‒mass spectrometry analysis. Computer aided (molecular docking SwissADME, AdmetSAR and pass prediction) analyses were undertaken to sort out the best-fit phytochemicals present in the plant responsible for antioxidant and anticancer effects. Among the fractions, the ethyl acetate fraction was the most abundant polyphenol-rich fraction and showed the highest antioxidant, reducing power, and free radical scavenging activities. Compared to untreated MCF-7 cells, ethyl acetate fraction-treated MCF-7 cells showed an increase in apoptotic characteristics, such as membrane blebbing, chromatin condensation, and nuclear fragmentation, causing apoptosis and decreased proliferation of HeLa and MCF-7 cells. Furthermore, gas chromatography mass spectrometry data revealed that the ethyl acetate fraction contained 16 compounds, including methyl esters of long-chain fatty acids, which are the major chemical constituents. Moreover, hexadecanoic acid, methyl ester; 9-octadecenoic acid (Z)-, methyl ester; 9,12-octadecadienoic acid, methyl ester (Z, Z) and phenol, 2,4-bis(1,1-dimethylethyl) are known to have antioxidant and cytotoxic activity, as confirmed by computer-aided models. A strong correlation was observed between the antioxidant and polyphenolic contents and the anticancer activity. In conclusion, we explored the possibility that L. aequata could be a promising source of antioxidants and anticancer agents with a high phytochemical profile.