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Abstract The objective was to investigate the effect of co-administration of hydrochlorothiazide and lisinopril as fixed dose combination on their intestinal absorption. The scope was extended to enhance intestinal absorption of both drugs. In situ rabbit intestinal absorption through the duodenum and jejuno-ileum was used to monitor membrane permeability of both drugs when perfused alone or in combination. Niosomes containing glycerols (glyceroniosomes) were loaded with both drugs. Glyceroniosomes comprised Span 60 or Tween 40 in combination with cholesterol and glycerol were prepared by bath sonication. Glyceroniosomes were characterized with respect to vesicle size, drug entrapment efficiency and were examined using transmission electron microscope (TEM). The prepared vesicles were nanosized spherical vesicles with average size of 202.4 nm and 108.8 nm for span free and span containing glyceroniosomes, respectively. The recorded Zeta potential values suggested good stability of the prepared formulations. Intestinal absorption studies reflected incomplete absorption of hydrocholothiazide and lisinopril correlating with their categorization as class IV and III drugs, respectively. Co-perfusion of both drugs reduced the intestinal absorption of lisinopril. Simultaneous encapsulation in glyceroniosomes enhanced the intestinal absorption of both drugs. Tween based systems were more efficient. The study introduced glyceroniosomes as carriers of simultaneous delivery of hydrochlorothiazide and lisinopril.

The study was conducted to evaluate the potential application of nanocapsules and nanospheres as topical drug delivery systems for indomethacin (as model drug). Both were prepared by nanoprecipitation using poly (ɛ-caprolactone) and hydroxypropyl β-cyclodextrin polymers and evaluated for morphology, particle size, zeta potential, EE% and in vitro drug release then incorporated in methylcellulose and Carbopol 940 gel bases and evaluated for in vitro release. The selected formulations and market product were evaluated for ex vivo human skin permeation and anti-inflammatory and analgesic activities by paw edema and hot plate methods respectively. Results showed that nanocapsules had slight higher EE% and larger particle sizes than nanospheres. In vitro release and zeta potential were nearly similar. Methylcellulose exhibited higher in vitro release than Carbopol 940 after 3 h (except NS2). Ex vivo skin permeation studies showed significant higher cumulative amount of IND (and flux) from NC1/MC and NS1/MC (1573.06 ± 14.23 µg/cm2 and 1452.24 ± 23.18 µg/cm2 respectively) than market product. They also showed enhancement ratio and permeability coefficient rate of ∼1.5 and ∼2 respectively. NC1/MC proved to be significantly higher pharmacodynamic effects than market product. All results showed that NC1/MC could provide a promising formula as a topical delivery of indomethacin.

Objective: Tilmicosin (TIL) is a long-acting macrolide antibiotic used to treat cattle for pathogens that cause bovine respiratory disease. However, overdoses of this medication have been reported to induce cardiac damage. Our experimental objective was to evaluate the protective effects of Spirulina platensis (SP) administration against TIL-induced cardiotoxicity in mice. Materials and Methods: Our experimental in vivo animal study used 40 male albino mice that were divided into five groups of eight mice per group. The first group served as a control group and was injected with saline. The second group received SP at dose of 1000 mg/kg body weight for five days. The third group received a single dose of TIL (75 mg/kg, subcutaneously). Groups 4 and 5 were given SP at doses of 500 and 1000 mg/kg body weight for five consecutive days just before administration of TIL at the same dose and regimen used for group 3. Results: TIL treated animals showed a significant increase in serum cardiac injury biomarkers as well as cardiac lipid peroxidation, however they had evidence of an inhibition in antioxidant biomarkers. SP normalized elevated serum levels of lactate dehydrogenase (LDH), creatine kinase (CK), and CK-MB. Furthermore, SP reduced TIL-induced lipid peroxidation and oxidative stress in a dose-dependent manner. Conclusion: Administration of SP minimized the toxic effects of TIL by its free radicalscavenging and potent antioxidant activity.

Abstract The phytochemical, nutritional, and biological features of wild carob pulp from Tanzight (TN), Ait-Waada (AW), and Tizi-ghnayn (TG) in Azilal were studied. The results of the study reveal that the carob pulp examined has a low-fat level. AW had the most total sugar (78.34 ± 3.00%), total reducing sugar (27.20 ± 2.89%), crude fiber (14.21 ± 1.23%), sucrose (24.303 ± 0.038%), sodium (153.7 ± 18.52 mg/kg), pH (5.599 ± 0.05), and total polyphenol content (4134.50 ± 17.91 mg GAE/100 g DW). TG has higher amounts of potassium (11373 ± 153.7 mg/kg), calcium (4345 ± 7.211 mg/kg), phosphorus (3551 ± 175.1 mg/kg), magnesium (1347 ± 52.43 mg/kg), fructose (7.635 ± 0.012%), and total flavonoids (1678.08 ± 24.05 mg RE/100 g DW). TN has the highest levels of crude protein (5.607 ± 0.047%), moisture (9.33 ± 0.57%), ash (4.16 ± 0.02%), glucose (2.956 ± 0.047%), and total condensed tannins (529.61 ± 6.76 mg CE/100 g DW). The ethanol extract derived from AW exhibited noteworthy antioxidant activity, as evidenced by its total antioxidant capacity (TAC) of 1245.83 ± 26.33 µg ascorbic acid equivalent /mg extract and IC50 values of 18.45 ± 1.41 µg/mL, 124.98 ± 5.21 µg/mL, and 24.87 ± 1.30 µmol/mL for 2,2-Diphenyl-1-picrylhydrazil (DPPH), beta carotene (β-Carotene), and 2,2’-azino-bis (3-éthylbenzothiazoline-6-sulfonate) (ABTS), respectively. Furthermore, AW has demonstrated significant antibacterial activity against a variety of bacterial and fungal strains using disc diffusion and broth dilution techniques. The analysed samples also demonstrated encouraging anti-cancer effects on MDA-MB-231, MDA-MB-436, and MCF-7 cancer cell lines. The biological activities were confirmed through molecular docking analysis, identifying naringin and quercetin 3-O-β-glucoside as related compounds. Additionally, ADME analyses have revealed that all the synthetic compounds examined in this study demonstrate high intestinal absorption, meet Lipinski’s criteria, indicating their potential suitability for oral drug development. Based on these findings, wild carob pulp from Azilal province may contain bioactive compounds and nutrients.

This study presents a novel approach to modeling breast cancer dynamics, one of the most significant health threats to women worldwide. Utilizing a piecewise mathematical framework, we incorporate both deterministic and stochastic elements of cancer progression. The model is divided into three distinct phases: (1) initial growth, characterized by a constant-order Caputo proportional operator (CPC), (2) intermediate growth, modeled by a variable-order CPC, and (3) advanced stages, capturing stochastic fluctuations in cancer cell populations using a stochastic operator. Theoretical analysis, employing fixed-point theory for the fractional-order phases and Ito calculus for the stochastic phase, establishes the existence and uniqueness of solutions. A robust numerical scheme, combining the nonstandard finite difference method for fractional models and the Euler-Maruyama method for the stochastic system, enables simulations of breast cancer progression under various scenarios. Critically, the model is validated against real breast cancer data from Saudi Arabia spanning 2004-2016. Numerical simulations accurately capture observed trends, demonstrating the model's predictive capabilities. Further, we investigate the impact of chemotherapy and its associated cardiotoxicity, illustrating different treatment response scenarios through graphical representations. This piecewise fractional-stochastic model offers a powerful tool for understanding and predicting breast cancer dynamics, potentially informing more effective treatment strategies.

Antibiotic resistance remains a critical challenge for public health. In this study, we investigate the antibacterial potential of Moroccan Allium sativum L. essential oil (EO) through both in vitro and in silico approaches. The EO was extracted using hydrodistillation, and its physicochemical properties were analyzed alongside its chemical composition via gas chromatography-mass spectrometry (GC/MS). We assessed antibacterial efficacy through disk diffusion assays targeting Escherichia coli (E. coli), methicillin-resistant Staphylococcus aureus (MRSA), and Pseudomonas aeruginosa (P. aeruginosa), and determined the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values. Finally, an in silico molecular docking analysis and ADMET (absorption, distribution, metabolism, excretion, and toxicity) prediction were performed. Our analysis identified 13 sulfur-based compounds within the EO, with diallyl disulfide (42.85 %), methylallyl disulfide (18.84 %), methylallyl trisulfide (15.38 %), and diallyl trisulfide (13.11 %) as major constituents. The EO demonstrated robust activity against MRSA, with an inhibition zone of 22 mm and an MIC of 0.75 mg/mL, whereas E. coli exhibited lower sensitivity, with an MIC of 1.51 mg/mL. Molecular docking analysis suggested that the primary sulfur compounds may effectively inhibit bacterial resistance-related enzymes. These findings highlight the potential of Allium sativum L. EO as a natural antibacterial agent, attributed largely to its sulfur compound content. This activity is likely linked with the EO's interaction with the complex structures of bacterial cell membranes, offering promise in combating resistant bacterial strains.

Abstract Bosentan is a drug used to treat pulmonary hypertension via dual endothelial receptor antagonism. Bosentan has a restricted oral bioavailability, a problem that's mostly due to poor solubility and hepatic metabolism. It is extensively used for the elderly and children who require a friendly dosage form like orodispersible tablets. So, the goal of this research work was to hasten the dissolution rate of bosentan to produce an orodispersible tablet with immediate drug release. Bosentan was exposed to ethanol-assisted kneading with a rise of xylitol or menthol concentrations (1:1 and 1:2 molar ratio of bosentan with excipient). In addition to observing the dissolution behavior, the resulting dry products were investigated using Fourier transform infrared spectroscopy (FTIR), differential thermal analysis (DTA), and X-ray diffraction (XRD). The FTIR reflected possible hydrogen bonding with xylitol and menthol. DSC studies reflected a reduction in the enthalpy and Tm. These results with XRD data reflected partial co-amorphization in the case of xylitol and eutaxia in the case of menthol. These modifications were related to an accelerated dissolving rate. The developed systems were fabricated as orodispersible tablets which exhibited immediate release of bosentan. Thus, the current study offered simple co-processing for the preparation of orodispersible bosentan tablets.

Abstract The use of a maximum power point (MPP) tracking (MPPT) controller is required for photovoltaic (PV) systems to extract maximum power from PV panels. However, under partial shading conditions, the PV cells/panels do not receive uniform insolation due to several power maxima appear on the PV array's P–V characteristic, a global MPP (GMPP) and two or more local MPPs (LMPPs). In this scenerio, conventional MPPT methods, including pertub and observe (P&O) and incremental conductance (INC), fail to differentiate between a GMPP and a LMPP, as they converge on the MPP that makes contact first, which in most cases is one of the LMPPs. This results in considerable energy loss. To address this issue, this paper introduces a new MPPT method based on the Seagull Optimization Algorithm (SOA) to operate PV systems at GMPP with high efficiency. The SOA is a new member of the bio-inspired algorithms. When compared to other evolutionary techniques, it uses fewer operators and modification parameters, which is advantageous when considering the rapid design process. In this paper, the SOA-based MPPT scheme is first proposed and then implemented for an 80 W PV system using the MATLAB/SIMULINK environment. The effectiveness of the SOA based MPPT method is verified by comparing its performance with P& O and PSO (particle swarm optimization) based MPPT methods under different shading scenarios. The results demonstrated that the SOA based MPPT method performs better in terms of tracking accuracy and efficiency.

Abstract One of the major challenges in photovoltaic (PV) systems is extracting the maximum power from the PV array, especially when they operate under partial shading conditions (PSCs). To address this challenge, this paper introduces a novel hybrid maximum power point tracking (MPPT) method based on grey wolf optimization and particle swarm optimization (GWO–PSO) techniques. The developed MPPT technique not only avoids the common disadvantages of conventional MPPT techniques (such as perturb and observe (P&O) and incremental conductance) but also provides a simple and robust MPPT scheme to effectively handle partial shading in PV systems, since it requires only two control parameters, and its convergence to the global maximum power point (GMPP) is independent of the search process's initial conditions. The feasibility and effectiveness of the hybrid GWO–PSO-based MPPT method are verified via a co-simulation technique that combines MATLAB/SIMULINK and PSIM software environments, while comparing its performance against GWO, PSO and P&O based MPPT methods. The simulation results carried out under dynamic environmental conditions have shown the satisfactory effectiveness of the hybrid MPPT method in terms of tracking accuracy, convergence speed to GMPP and efficiency, compared to other methods.

In Morocco, the flower buds of Syzygium aromaticum L (Clove) from Myrtaceae are essential in traditional medicine; they are used in many forms (infusion, maceration, and essential oil) and are suggested to mitigate inflammatory conditions such as muscle and dental pain as well as rheumatic diseases. This study aims to chemically characterize the aqueous and ethanolic extracts as well as the essential oil from cloves; also, we aimed to evaluate their effects on the bactericidal activity of human neutrophils compared with eugenol. The chemical composition of extracts was evaluated via qualitative phytochemical screening followed by quantitative screening using spectrophotometry and HPLC technique. The essential oil was analyzed by the GC-MS technique. The PMNs bactericidal activity of extracts, essential oil, and eugenol was carried out by MTT assay. The screening of extracts showed the presence of phenols, flavonoids, flavones aglycones, coumarins, and tannins. HPLC analysis revealed the presence of numerous phenolic compounds such as gallic acid, rutin, and quercetin while the GC-MS analysis of essential oil showed that the main components are eugenol (78.67%), eugenyl acetate (11.77%), and caryophyllene (6.85%). The aqueous, ethanolic extracts and essential oil showed an immunomodulatory activity by exerting a significant inhibition of neutrophil bactericidal activity in a dose dependent-manner reaching maximal inhibition at the concentration of 200 µg/ml with only 29.92%, 32.24%, and 48.15%, respectively (p

ObjectiveEvidence-based characterization of the diagnostic and prognostic value of the hematological and immunological markers related to the epidemic of Coronavirus Disease 2019 (COVID-19) is critical to understand the clinical course of the infection and to assess in development and validation of biomarkers.MethodsBased on systematic search in Web of Science, PubMed, Scopus, and Science Direct up to April 22, 2020, a total of 52 eligible articles with 6,320 laboratory-confirmed COVID-19 cohorts were included. Pairwise comparison between severe versus mild disease, Intensive Care Unit (ICU) versus general ward admission and expired versus survivors were performed for 36 laboratory parameters. The pooled standardized mean difference (SMD) and 95% confidence intervals (CI) were calculated using the DerSimonian Laird method/random effects model and converted to the Odds ratio (OR). The decision tree algorithm was employed to identify the key risk factor(s) attributed to severe COVID-19 disease.ResultsCohorts with elevated levels of white blood cells (WBCs) (OR = 1.75), neutrophil count (OR = 2.62), D-dimer (OR = 3.97), prolonged prothrombin time (PT) (OR = 1.82), fibrinogen (OR = 3.14), erythrocyte sedimentation rate (OR = 1.60), procalcitonin (OR = 4.76), IL-6 (OR = 2.10), and IL-10 (OR = 4.93) had higher odds of progression to severe phenotype. Decision tree model (sensitivity = 100%, specificity = 81%) showed the high performance of neutrophil count at a cut-off value of more than 3.74x109/L for identifying patients at high risk of severe COVID-19. Likewise, ICU admission was associated with higher levels of WBCs (OR = 5.21), neutrophils (OR = 6.25), D-dimer (OR = 4.19), and prolonged PT (OR = 2.18). Patients with high IL-6 (OR = 13.87), CRP (OR = 7.09), D-dimer (OR = 6.36), and neutrophils (OR = 6.25) had the highest likelihood of mortality.ConclusionsSeveral hematological and immunological markers, in particular neutrophilic count, could be helpful to be included within the routine panel for COVID-19 infection evaluation to ensure risk stratification and effective management.

The mapping of soil nutrients is a key issue for numerous applications and research fields ranging from global changes to environmental degradation, from sustainable soil management to the precision agriculture concept. The characterization, modeling and mapping of soil properties at diverse spatial and temporal scales are key factors required for different environments. This paper is focused on the use and comparison of soil chemical analyses, Visible near infrared and shortwave infrared VNIR-SWIR spectroscopy, partial least-squares regression (PLSR), Ordinary Kriging (OK), and Landsat-8 operational land imager (OLI) images, to inexpensively analyze and predict the content of different soil nutrients (nitrogen (N), phosphorus (P), and potassium (K)), pH, and soil organic matter (SOM) in arid conditions. To achieve this aim, 100 surface samples of soil were gathered to a depth of 25 cm in the Wadi El-Garawla area (the northwest coast of Egypt) using chemical analyses and reflectance spectroscopy in the wavelength range from 350 to 2500 nm. PLSR was used firstly to model the relationship between the averaged values from the ASD spectroradiometer and the available N, P, and K, pH and SOM contents in soils in order to map the predicted value using Ordinary Kriging (OK) and secondly to retrieve N, P, K, pH, and SOM values from OLI images. Thirty soil samples were selected to verify the validity of the results. The randomly selected samples included the spatial diversity and characteristics of the study area. The prediction of available of N, P, K pH and SOM in soils using VNIR-SWIR spectroscopy showed high performance (where R2 was 0.89, 0.72, 0.91, 0.65, and 0.75, respectively) and quite satisfactory results from Landsat-8 OLI images (correlation R2 values 0.71, 0.68, 0.55, 0.62 and 0.7, respectively). The results showed that about 84% of the soils of Wadi El-Garawla are characterized by low-to-moderate fertility, while about 16% of the area is characterized by high soil fertility.

The authors wish to make the following corrections to this paper [1]: Due to mislabeling, replace: Figure 6Typical Neolithic settlements in the Tavoliere delle Puglie: (a) settlement of Masseria Schifata; (b) settlement of Passo di Corvo [36] [...]

The use of satellite radar in landscape archaeology offers great potential for manifold applications, such as the detection of ancient landscape features and anthropogenic transformations. Compared to optical data, the use and interpretation of radar imaging for archaeological investigations is more complex, due to many reasons including that: (i) ancient landscape features and anthropogenic transformations provide subtle signals, which are (ii) often covered by noise; and, (iii) only detectable in specific soil characteristics, moisture content, vegetation phenomenology, and meteorological parameters. In this paper, we assessed the capability of SAR Sentinel 1 in the imaging and detection of palaeo-landscape features in the Mediterranean area of Tavoliere delle Puglie. For the purpose of our investigations, a significant test site (larger than 200 km2) was selected in the Foggia Province (South of Italy) as this area has been characterized for millennia by human frequentation starting from (at least) the Neolithic. The results from the Sentinel 1 (S-1) data were successfully compared with independent data sets, and the comparison clearly showed an excellent match between the S-1 based outputs and ancient anthropogenic transformations and landscape features.

This paper is focused on the use of satellite Sentinel-2 data for assessing their capability in the identification of archaeological buried remains. We selected the “Tavoliere delle Puglie” (Foggia, Italy) as a test area because it is characterized by a long human frequentation and is very rich in archaeological remains. The investigations were performed using multi-temporal Sentinel-2 data and spectral indices, commonly used in satellite-based archaeology, and herein analyzed in known archaeological areas to capture the spectral signatures of soil and crop marks and characterize their temporal behavior using Time Series Analysis and Spectral Un-mixing. Tasseled Cap Transformation and Principal Component Analysis have been also adopted to enhance archaeological features. Results from investigations were compared with independent data sources and enabled us to (i) characterize the spectral signatures of soil and crop marks, (ii) assess the performance of the diverse spectral channels and indices, and (iii) identify the best period of the year to capture the archaeological proxy indicators. Additional very important results of our investigations were (i) the discovery of unknown archaeological areas and (ii) the setup of a database of archaeological features devised ad hoc to characterize and categorize the diverse typologies of archaeological remains detected using Sentinel-2 Data.