Search

Mnaza Noreen,1 Muhammad Bilal,1,2 Muhammad Usman Qamar,3,4 Nasir Rasool,1 Abid Mahmood,5 Sobia Umar Din,1 Tawaf Ali Shah,6 Yousef A Bin Jardan,7 Mohammed Bourhia,8 Lahcen Ouahmane9 1Department of Chemistry, Government College University Faisalabad, Faisalabad, 38000, Pakistan; 2School of Chemistry and Chemical Engineering, Shandong University, Jinan, 250100, People’s Republic of China; 3Institute of Microbiology, Faculty of Life Sciences, Government College, University Faisalabad, Faisalabad, 38000, Pakistan; 4Division of Infectious Disease and Department of Medicine, University of Geneva, Geneva, Switzerland; 5Department of Pharmaceutical Chemistry, Government College University Faisalabad, Faisalabad, 38000, Pakistan; 6College of Agriculture Engineering and Food Science, Shandong University of Technology, Zibo, 25500, People’s Republic of China; 7Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; 8Department of Chemistry and Biochemistry, Faculty of Medicine and Pharmacy, Ibn Zohr University, Laayoune, 70000, Morocco; 9Laboratory of Microbial Biotechnologies, Agrosciences and Environment (Biomage), Labeled Research Unit-CNRSTN° 4, Cadi Ayyad University, Marrakesh, 40000, MoroccoCorrespondence: Nasir Rasool; Mohammed Bourhia, Email nasirrasool@gcuf.edu.pk; m.bourhia@uiz.ac.maIntroduction: New Delhi Metallo-β-lactamase producing Klebsiella pneumoniae (NDM-1-KP) sequence type (ST) 147 poses a significant threat in clinical settings due to its evolution into two distinct directions: hypervirulence and carbapenem resistance. Hypervirulence results from a range of virulence factors, while carbapenem resistance stems from complex biological mechanisms. The NDM-1-KP ST147 clone has emerged as a recent addition to the family of successful clones within the species.Methods: In this study, we successfully synthesized 5-bromo-N-alkylthiophene-2-sulfonamides ( 3a-c) by reacting 5-bromothiophene-2-sulfonamide ( 1) with various alkyl bromides ( 2) using LiH. We also synthesized a series of compounds ( 4a-g) from compound ( 3b) using the Suzuki-Miyaura cross-coupling reaction with fair to good yields (56– 72%). Further, we screened the synthesized molecules against clinically isolated New Delhi Metallo-β-lactamase producing Klebsiella pneumoniae ST147. Subsequently, we conducted in-silico tests on compound 3b against a protein extracted from NDM-KP ST147 with PDB ID: 5N5I.Results: The compound ( 3b) with favourable drug candidate status, MIC of 0.39 μg/mL, and MBC of 0.78 μg/mL. This low molecular weight compound exhibited the highest potency against the resistant bacterial strains. The in-silico tests revealed that the compound 3b against a protein extracted from NDM-KP ST147 with PDB ID: 5N5I demonstrated H-bond and hydrophobic interactions.Conclusion: The 5-bromo-N-alkylthiophene-2-sulfonamides displayed antibacterial efficacy against New Delhi Metallo-β-lactamase producing Klebsiella pneumoniae ST147. After the in-vivo trial, this substance might offer an alternative therapeutic option. Keywords: NDM-1, antibacterial, drug resistance, Klebsiella pneumoniae, ST, sulfonamides

Solubility enhancement of poorly aqueous-soluble drugs, like Terbinafine (TBN), is a critical challenge in formulating effective dosage forms. This study focused on developing β-cyclodextrin (β-CD) and polyacrylamide (PAM)-based microgels to address the solubility issue of TBN, classified as a biopharmaceutics classification system class II drug. The microgels were crafted through free radical polymerization, employing methylene bisacylamide as a cross-linker and methacrylic acid as a monomer, initiated by ammonium persulfate. Comprehensive characterizations, including Fourier transform infrared, thermo-gravimetric analysis, differential scanning calorimetry, scanning electron microscopy, powder X-ray diffractometry analysis, Zeta size, and Zeta potential, were conducted. In vitro studies, such as drug release and swelling, were performed at pH 1.2. Toxicity analysis in rabbits revealed zero toxicity. These β-CD/PAM microgels successfully enhanced the solubility of TBN.

Citronellol (CT) is a monoterpene alcohol present in the essential oil of plants of the genus Cymbopogon and exhibits diverse pharmacological activities. The aim of the current study was to investigate the hepatoprotective potential of CT against ethanol-induced toxicity in HepG2 cell lines. Silymarin (SIL) was used as a standard drug. MTT, crystal violet assay, DAPI, and PI staining were carried out to assess the effect of ethanol and CT on cell viability. RT-PCR determined the molecular mechanisms of hepatoprotective action of CT. CT ameliorated cell viability and restricted ethanol-induced cell death. DAPI and PI staining showed distinct differences in cell number and morphology. Less cell viability was observed in the diseased group obviously from strong PI staining when compared to the CT- and SIL-treated group. Moreover, CT showed downregulation of interleukin (IL-6), transforming growth factor-beta 1 (TGF-β1), collagen type 1 A 1 (COL1A1), matrix metalloproteinase-1 (MMP-1), tissue inhibitor of metalloproteinase-1 (TIMP-1) and glutathione peroxidase-7 (GPX-7) levels. Molecular docking studies supported the biochemical findings. It is concluded that the cytoprotective activity of CT against ethanol-induced toxicity might be explained by its anti-inflammatory, immunomodulatory, and collagen-regulating effects.

The purpose of the current study is to assess the chemical profile, antioxidant, antimicrobial, and insecticide efficacy of essential oil derived from the leaf of Moroccan Mentha aquatica L. (MA-EO) using in vitro and in silico analysis. Using GC-MS/MS analysis, 18 components of MA-EO were identified, including linalool (42.42%), α-elemol (10.45%), α-terpineol (8.07%), linalyl acetate (7.37%), and caryophyllene (4.05%). Additionally, MA-EO has a strong antioxidant capacity with IC50 values of 0.64 ± 0.01 µg/mL using the DPPH assay and 0.167 ± 0.13 µg/mL using the ABTS test. Total antioxidant capacity activities were found to be 188.21 ± 0.31 mg EAA/g, while RP activities were 1.95 ± 0.023. The powerful antibacterial properties of MA-EO were proven to be effective against Escherichia coli and Candida albicans. MA-EO showed insecticidal potential using the fumigation experiment, with an LC50 of 3.33 μL/L in the air after 24 h of exposure. At a dose of 20 µL/mL, MA-EO reduced fertility, fecundity, and emergence of adult C. maculatus. MA-EO had 95% mortality at the same dosage. In silico analysis revealed that the antioxidant activity of MA-EO is linked to γ-eudesmol, while its antibacterial efficacy is associated with phenol, 2,4-di-tert-butyl-, and its antifungal capacity with phenol, 2,4-di-tert-butyl-. MA-EO demonstrates potent bactericidal, fungicidal, and bioinsecticide properties, making it effective for controlling bacteria, fungi, and insect pests in stored grains.

Breast cancer is the biggest cause of death among women worldwide. Natural chemicals from medicinal plants offer promise for cancer therapy. This research screens 29 Dryopteris species plant-derived chemicals, mostly phloroglucinols, for breast cancer therapy potential. First, we used Gaussian09 and DFT/B3LYP/6-311+G(d, p) calculations to evaluate compound stability and reactivity. We conducted molecular docking experiments to identify drugs with high binding affinity for the PI3Kα protein’s active pocket. DJ1–DJ22 were found to be the most effective PI3Kα inhibitors, with energies ranging from −8.0 to −9.2 kJ/mol. From in silico pharmacokinetic and bioactivity screening, DJ3, DJ7, and DJ18 were identified as promising PI3Kα inhibitors. PI3Kα backbone stability was tested in a water model using molecular dynamics simulations employing DJ3, DJ7, DJ18, and Trastuzumab as a pharmacological reference. Synthesis of target-hit DJ3, DJ7, and DJ18 derivatives may lead to breast cancer drug-like molecules for related cancers. The work uses in silico methods to find natural phloroglucinols for breast cancer therapy, enabling new chemotherapeutic drugs.

Acute myeloid leukemia (AML) takes center stage as a highly prevalent and aggressive clonal disorder affecting hematological stem cells. FMS-like tyrosine kinase 3 (FLT3) mutations were prevalent in nearly 30% of the AML cases. However, efforts have led to the development of anti-mutant FLT3 drugs, such as midostaurin, gilteritinib, and quizartinib, to improve treatments. Currently, we are exploring the ability of compounds from anti-leukemic plants to be used in AML therapies, focusing on mutant FLT3 inhibition. Employing computational techniques such as drug-likeness assessment, molecular docking, pharmacokinetics properties profiling, molecular dynamics simulations (MDS), and free energy calculations, we identified 43 out of 57 compounds with oral drug potential. Notably, 7 out of 43 compounds, including flavopiridol, sanggenol Q, norwogonin, oblongixanthones A, oblongixanthones B, apigenin, and luteolin exhibited strong binding affinities ranging from −9.0 to −9.8 kcal/mol, surpassing the control drug gilteritinib (−6.3 kcal/mol). Notably, flavopiridol and norwogonin displayed highly favorable pharmacokinetics and low toxicity profiles. MDS confirmed the stability of their binding through parameters such as root mean square deviation, root mean square fluctuation, and radius of gyration (R g) over 100 ns simulations. Flavopiridol and norwogonin emerge as promising candidates for the development of mutant FLT3 inhibitors. Therefore, experimental studies are warranted to validate their therapeutic potential.

The treatment of the various infections caused by Staphylococcus aureus has become challenging due to the evolving resistance against current therapeutics. In this study, the potentials of napthyridine and oxadiazole derivatives to serve as dual inhibitors of penicillin-binding protein 2a (PBP-2a) and FemA protein, which are crucial to resistance to methicillin-based drugs by S. aureus, were evaluated using molecular modeling techniques. Seventy-two compounds were subjected to molecular docking against the proteins, and the hit compounds were subjected to drug-likeness evaluation and in silico pharmacokinetics prediction. The compounds with good safety profiles were subjected to a 250-ns molecular dynamics (MD) simulation and other relevant analyses based on the MD trajectories. Five hit compounds were selected based on their high affinity for the targets as evidenced by their docking scores ranging from −8.6 to −10.1 kcal/mol for PBP-2a and −9.6 to −9.9 kcal/mol for FemA. These compounds also passed Lipinski’s rule of five evaluation with no violation and possessed high human intestinal absorption potential, showcasing their potential as orally administered therapeutic agents. However, three of the compounds were potential mutagens. MD simulation revealed that the final two compounds maintained stable interactions with the target proteins over 250 ns, with minimal deviations and fluctuations. Hydrogen bond stability and energy decomposition analysis further confirmed the strong binding affinity of the hit compounds compared to the control drug, methicillin. Conclusively, the compounds with the CID “135964525” and “44130718” are worthy of further experimental validation in the development of potential inhibitors of PBP-2a and FemA.

This study aims to assess the chemical composition of the aqueous extract of Cistus albidus L. leaves, as well as the potential of aqueous and hydroethanol extracts of the leaves and seeds as analgesic, anti--inflammatory, and antioxidant agents. The contents of phenolics and inorganic constituents were determined in C. albidus seeds and leaves; antioxidant capacity was assessed by 3 complementary and diverse tests. The carrageenan-induced paw edema technique was used to investigate the anti-inflammatory effect in vivo, and albumin denaturation to evaluate the anti-inflammatory effect in vitro. The acetic acid-induced contortion test, the tail-flick test, and the plantar test were used to assess the analgesic effi cacy in vivo.

This study evaluated the volatile components of Cannabis sativa L. essential oils (CSEOs) and their pharmacological potential in vitro, in animal, and in silico. The anti-oxidant capacities of volatile compounds were tested using 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP), total anti-oxidant capacity (TAC), and gas chromatography-mass spectrometry (GC-MS). Anti-microbial activity against bacterial and fungal strains was assessed using disk diffusion and micro-dilution, and acute toxicity was examined on mice using OECD 423 criteria. The results indicate that the main components were β-caryophyllene (31.54%), α-humulene (12.62%), β-myrcene (4.83%), and α-pinene (4.69%). The essential oil showed high anti-oxidant ability (IC50 = 0.981 ± 0.059 mg/ml for DPPH, EC50 = 1.74 ± 0.05 for FRAP), and TAC of 0.101 ± 0.001 mg AAE/g. Additionally, it showed significant antibacterial action against Gram-negative organisms, such as Escherichia coli (11.33 ± 0.00 mm), Klebsiella pneumonia (9 ± 0.00 mm), and Pseudomonas aeruginosa (9.34 ± 0.00), with MICs ranging from 0.0052 to 0.0208 mg/CSEO demonstrated antifungal activity against Candida albicans and Fusarium proliferatum, with activity levels of 18.66 ± 0.88 mm, 41.89 ± 3.60%, and MICs of 0.39 and 0.013 mg/ml, respectively. In toxicological studies, CSEO proved to be safe for animals. Docking identified bioactive components and explored anti-oxidant and antibacterial properties. Docking proved that bulnesol and champacol caused indicated actions.

This research study’s objective was to formulate interpenetrating pH-sensitive polymeric networks interpenetrating networks (IPNs) based on hydroxypropylmethylcellulose (HPMC)/Primojel for use in the treatment of various malignant conditions. For controlled release, letrozole (LTZ) was selected as a model drug in HPMC and Primojel-based IPN hydrogels. HPMC and Primojel based IPN hydrogels were fabricated through the free radical polymerization method by utilizing HPMC and Primojel as polymers, methacrylic acid as monomer, ammonium persulfate as initiator, and methylenebisacrylamide as cross-linker. For structural characterization, various techniques such as Fourier transform infrared spectroscopy, Scanning electron microscopy (SEM), DSC, TGA, and Powder x-ray diffraction (PXRD) were applied to IPN samples. In vitro and swelling studies were also employed to observe the response of these polymeric networks against 1.2 and 7.4 pH. TGA and DSC of an optimized loaded formulation possess better thermal stability as compared to individual drug. PXRD depicted minor crystallinity and a significant amorphous nature. SEM images show that polymeric networks possess an uneven and porous surface. Significant swelling and enhanced in-vitro outcomes at a high pH of 7.4 confirmed the IPN pH responsive properties. Toxicological studies performed on rabbits revealed no harm in the results. Thus, IPN based on HPMC/Primojel was successfully synthesized and can be used for LTZ’s controlled release.

To help discover a reasonable and eco-friendly insecticide, we undertook a study on the insecticidal potential of carvacrol and essential oils extracted by hydrodistillation using a Clevenger apparatus from the plant species Nigella sativa seeds essential oils of Nigella sativa (EONS) on Callosobruchus maculatus adults. Several tests including contact toxicity, repellent effect, topical contact test, and inhalation effect were conducted. Adults of C. maculatus have been exposed to the toxic effects of different concentrations of these essential oils as well as with carvacrol. The results obtained showed that both EONS and carvacrol exhibited a moderate repellent effect (class II) on C. maculatus adults. EONS showed the highest toxicity by inhalation test, with an LD50 of 13.386 and an LD95 of 33.186 μL/cm2, compared to carvacrol (LD50 = 21.509 and LD95 = 38.877 μL/cm2). The EONS by contact test exhibited more toxic effects, with an LD50 of 23.350 µL/100 g and an LD95 of 45.315 µL/100 g, compared to carvacrol (LD50 = 27.853 µL/100 g and LD95 = 45.184 µL/100 g). For the topical contact test results, carvacrol was more toxic, with an LD50 of 3.915 and an LD95 of 7.696 µL/mL, compared to EONS (LD50 = 14.509 and LD95 = 25.516 µL/mL). The high toxicity of EONS can be explained by the presence of 25.8% of o-cymene, 8.53% of cyclofenchene, and 7.71% of beta-pinene, as well as 4.6% of carvacrol, in its chemical composition. Unmitigatedly, these data suggest that the essential oils of N. sativa may present a raw material for the development of new bio-insecticidal products against C. maculatus, one of the main pests of stored foodstuffs.

This research aimed to prepare and characterize a new type of polymeric cross-linked topical hydrogel patches for the treatment of wound infections. The free radical polymerization method was used to prepare the topical hydrogel patches by utilizing natural polymers, i.e., agarose and gelatin. These natural polymers were chemically cross-linked with monomer (acrylic acid) using ammonium persulfate as an initiator via the cross-linker N,N methylene bisacrylamide. An antibiotic, i.e., gentamicin sulfate was loaded into a designed polymeric system. The polymeric cross-linked topical hydrogel patches were made in a spherical shape, which was revealed to be stable and elastic. Fourier transform infrared spectroscopy, scanning electron microscopy, differential scanning calorimetry, thermogravimetric analysis, and X-ray powder diffraction investigation were used to characterize the topical hydrogel patches. Polymeric cross-linked hydrogel patches were evaluated for their sol–gel analysis, swelling studies, in vitro drug release studies against pH 5.5, 6.5, and 7.4, ex vivo drug permeation, and the deposition study on the rabbit’s skin by using a Franz diffusion cell. In addition, the skin irritation study and wound healing performance of drug-loaded topical patches were also assessed and compared to commercially available formulations. The topical hydrogel patches were found to be non-irritating to the skin for up to 72 h as determined by a Draize patch test and when compared to marketed formulations, these topical patches resulted in faster wound healing. The prepared formulation showed promising potential for the treatment of skin wound infection.

Cytisus villosus Pourr. (C. villosus) is a medicinal plant belonging to the Fabaceae family, which grows in the Mediterranean area. It is used in traditional medicine against diseases related to inflammation. The objective of the present study was to identify the mineral and polyphenolic composition as well as to evaluate some biological properties including antioxidant, anti-inflammatory, and analgesic activities of C. villosus leaf aqueous extract. The chemical constituents were identified and quantified using ultra performance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS) methods. The antioxidant properties of C. villosus leaves were tested using reducing power (RP), 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS), and 2,2′-diphenyl-1-picrylhydrazyl (DPPH) assays. The anti-inflammatory potency was evaluated in vitro and in vivo using the albumin denaturation test and the carrageenan test, respectively. Furthermore, the analgesic effect was performed in vivo using tail flick, acetic acid-induced contortion, and plantar tests. Mineralogical analysis revealed that potassium and calcium were the most abundant minerals. The analysis and quantification of the phytochemical composition using UPLC-ESI-MS/MS showed that quinic acid (57.478 ± 1.72 mg/kg) was the major compound of the aqueous extract, followed by salicylic acid (17.38 ± 0.2 mg/kg), isoquercetin (16.895 ± 1.01 mg/kg), and gallic acid (15.914 ± 1.51 mg/kg). The extracts showed potent antioxidant activity for all tests used. The highest antioxidant activity was recorded for the DPPH, ABTS and RP methods, with an IC50 of 3.94 ± 0.09, 2.88 ± 0.07, and 1.94 ± 0.10 μg/mL, respectively. Additionally, using the most frequent analgesic assays, the aqueous extract at a dose of 500 mg/kg exhibited a potent analgesic activity. Notably, an interesting inhibition of albumin denaturation was recorded with an IC50 of 383.94 μg/mL, corroborating the in vivo test. Overall, the results presented here may represent a scientific basis for the traditional use of C. villosus in the treatment of inflammation-related diseases.

Juniperus phoenicea (L.) is a medicinal plant that has been used in phytotherapy as a treatment of certain pathological infections. In this context, the present work aimed to valorize the essential oil of J. phoenicea seeds (EOGP) by studying its chemical composition, and antioxidant and antimicrobial activities. The EOGP was extracted by use of hydrodistillation and characterized by gas chromatography (GC–MS). The antioxidant power was evaluated by three methods (TAC, DPPH, and FRAP). The antimicrobial power was evaluated against Staphylococcus aureus (ATCC6633), Escherichia coli (K12), Bacillus subtilis (DSM6333), Proteus mirabilis (ATCC29906), Candida albicans (ATCC10231), Aspergillus niger (MTCC282), Aspergillus flavus (MTCC9606), and Fusarium oxysporum (MTCC9913). The GC/MS results revealed a total identification of 99.98% with a dominance of carvacrol (39.81%) followed by p-cymen-3-ol (34.44%) and o-cymene (13.60%). Findings showed that EOGP exhibited important antioxidant power as IC50 was determined to be 26 µg/mL for 2,2-diphenyl-1-picrylhydrazyl, while EC50 was 216.34 µg/mL for ferric reducing antioxidant power and total antioxidant capacity was 720 mg AAE/g. The antimicrobial power on solid medium revealed that the inhibition diameters ranged from 11.30 ± 0.58 to 20 mm for the bacterial strains and from 9.33 ± 0.57 to 54.43 ± 0.29 mm for fungi. Notably, minimum inhibitory concentrations ranged from 18 to 19 µg/mL for bacterial strains and from 5.04 to 10.09 µg/mL for fungal strains. Overall, our results demonstrated the importance of EOGP as a source of natural antioxidant and antibacterial medicines against clinically relevant pathogenic strains.

The objective of this work was to characterize the phytochemical composition of essential oil from Juniperus thurifera (L.) fruits (EOFT) and study its antioxidant, antibacterial, and antifungal effects. EOFT was extracted by hydrodistillation and fingerprinted by using GC–MS. The antioxidant effect of EOFT was evaluated using 2,2-diphenylpicrylhydrazyl (DPPH), ferric iron reduction assay (FRAP), and total antioxidant capacity (TAC) assays. Importantly, the antimicrobial activity of EOFT was performed against Candida albicans, Aspergillus niger, Aspergillus flavus, Fusarium oxysporum, Staphylococcus aureus, Escherichia coli, Bacillus subtilis, and Proteus mirabilis. In addition, the inhibitory capacity of NADPH oxidase and human acetylcholinesterase was also investigated using molecular docking. The results of the chemical composition reveal that EOFT constituted 11 terpenic compounds with dominance of elemol (33.86%), terpinen-4-ol (27.80%), and cryptomeridiol (18.36%). The antioxidant power of EOFT recorded IC50 values of 197.07 ± 0.09 μg/mL (DPPH) and 216.34 ± 0.06 μg/mL (FRAP), while TAC of EOFT was determined to be 181.06 μg AAE/mg. The antibacterial potency on solid medium revealed that EOFT induced inhibition zone diameters reaching 14 mm, and a minimum concentration up to 2.78 µg/mL against the studied bacterial strains. The EOFT also showed an important antifungal effect as the inhibition reached 42%, and the MIC was between 7.50 and 22.25 µg/mL. The in silico study showed that o-Cymene was the most active molecule against NAD(P)H oxidase followed by cadinol with a Glide score of −5.344 and −5.143 kcal/mol, respectively. Due to their promising results, the outcome of this work suggests that EOFT could be used as an interesting natural weapon to control microbial and freed radical-related diseases.

Multiple stresses in waste dumpsite soils can drive antibiotic production as one of the strategies for survival. Bacteria are the most prolific producers of antibiotics. This study investigated the antibiotic production potential of bacteria isolated from Bahir Dar city municipal solid waste dumpsite (MSWDS). Bacteria were isolated from soil collected from the dumpsite on starch casein or nutrient agar. The isolates were carefully screened for antimicrobial activity against six pathogenic bacterial test strains. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were also determined from cell-free metabolites of the most promising isolates. Isolates showing antimicrobial activity were identified using cultural and biochemical methods. A total of 143 distinctive colonies were obtained and tentatively identified to 13 bacterial genera. Twenty-six (18.18%) of the isolates (six Bacillus and 20 actinobacteria related) demonstrated antimicrobial activities at least against one of the tested bacterial strains. These isolates were related to two actinobacterial and 11 other bacterial genera. Seven out of 26 isolates showed a broad-spectrum of antibiotic activities. Two isolates, which showed a wide spectrum, were selected for the MIC and MBC tests against Escherichia coli and Staphylococcus aureus. The MIC and MBC of the isolates were recorded to be 250–500 µg/mL against the test strains. Bahir Dar city MSWDS contained a high incidence of antibiotic-producing bacteria. Strain level identification of the isolates and detailed characterization of the metabolites will give a good insight into the antimicrobial production potential in the waste dumpsite.

The objective of the current research was to identify and evaluate the possibility of production of pectinase, also known as pectin degrading enzymes, from indigenous bacterial strains. Qualitative screening of isolated bacterial strains showed that among 29 bacterial strains, 5 have maximum enzymatic activity. The highest pectinase producing strains were quantitatively analyzed for enzyme production. SH7 strain was found as highest pectinase producer (0.77 IU/mL) that was further analyzed to molecular level by amplification of 16s rRNA. It was found 100% similar with other reported strains of Bacillus thuringiensis. Medium optimization was performed to optimize fermentation conditions for maximum enzyme yield. An experimental design containing 12 experimental runs was designed by Plackett–Burman design (PBD). Maximum pectinase activity was obtained at 45°C after 24 h when the growth medium was supplemented with 2.5% nitrogen, 5.0% substrate, MgSO4 as metal ion, 1% inoculum size, and pH was adjusted to 6. Factorial regression analysis of the PBD design was performed and the overall design was also found significant in terms of R square value. In PBD, the most significant factors for production were temperature, pH, metal ion concentration, and nitrogen source. Central composite design (CCD) design consisting of 26 experimental runs was employed to optimize these four significant factors. The overall model summary showed maximum pectinase activity (19.2 IU/mL) at 37°C temperature, 0.08 NaCl, 1.7% nitrogen source, and pH 8.4. In CCD, NaCl, nitrogen source, and pH were also reported as significant factors by the Pareto chart, probability plots, and 3D interactions.

Berberis hispanica Boiss. & Reut (B. hispanica) belongs to the family Berberidaceae, which is currently used in traditional medicines. This article aimed to study the phytochemical composition and acute and subacute toxicity of B. hispanica extract in rats. The phytochemical composition of B. hispanica extract was characterized using GC-MS. The acute toxicity was investigated in vivo via the oral administration of single doses including 400, 800, 1,000, 1,200, and 1,400 mg/kg for 14 days. The subchronic toxicity was studied through oral administration of 400 mg/kg for 60 days. The findings of the phytochemical analysis of B. hispanica extract showed the presence of various phytochemical compounds. Acute toxicity results revealed serious clinical symptoms and mortalities in rats treated with 800 mg/kg up to a maximum of 1,400 mg/kg. With acute toxicity, subchronic toxicity results showed also serious signs of toxicity including biochemical and histological alterations in animals treated with 1,400 mg/kg. B. hispanica extract revealed to be toxic in rats orally treated under both subacute (>400 mg/kg) and subchronic toxicity conditions (400 mg/kg). The outcome of this study serves the society as it provides toxicological evidence of B. hispanica used in alternative medicines

Autoimmune diseases are pathological conditions in which the immune system mistakenly attacks its own tissues. This study evaluates the performance of two techniques, which are identifiers of autoantibody specifics: immunoblot and immunodot. This study was conducted in 300 patients of whom 62 were tested positive for antinuclear antibodies. The patients were initially screened for antinuclear antibodies using indirect immunofluorescence. Then, the identification of specific autoantibodies such as anti-extractable nuclear antigens (ENAs) was carried out using the immunoblot and immunodot techniques. The results showed that immunoblot and immunodot did not present a significant difference in their sensitivity against anti-SSA/52, SSB, CENP-B, PCNA, U1-snRNP, Jo-1, Pm-scl, and Mi-2 (p > 0.05). However, the two techniques showed a significant difference in their sensitivity toward autoantibodies anti-DNAn, anti-histone, anti-SmD1, and anti-ds-DNA (p < 0.05). The immunoblot data were in complete accordance with the immunodot data (100%) regarding the detection of autoantibodies such as anti SSA/52, SSB, CENP-B, PCNA, U1-snRP, Jo-1, Pm-scl, and Mi-2, 80% regarding SmD1, and 75% concerning ds-DNA. We should certainly pay closer attention to the efficiency of the techniques used in the diagnosis of autoimmune diseases.

Citrullus colocynthis (L.) Schrad (C. colocynthis) called colocynth is a wild species that belongs to the family cucurbitaceae. The present research work aimed to study the phytochemical composition, cytotoxic and antioxidant activities of C. colocynthis seed extract. The chemical characterization of C. colocynthis seeds was effectuated using a gas chromatograph coupled to a mass spectrometer (GC-MS). The cytotoxic activity of C. colocynthis seed extract against breast cancer cell lines (MDA-MB-231) and colon cancer cell lines (HT-29) was assessed using the WST-1 bioassay. The antioxidant power was evaluated by the DPPH assay. The phytochemical characterization of C. colocynthis seed extract showed the richness of C. colocynthis seed extract in several families of bioactive compounds. Regarding the cytotoxic activity, the IC50 (the half-maximal inhibitory concentration) of C. colocynthis seed extract in inhibiting MDA-MB-231 and HT-29 were 170.34 and 132.31 µg/mL, respectively. The cancerous cell lines MDA-MB-231 seem to be more sensitive to C. colocynthis seed extract than HT-29 cell lines. C. colocynthis seed extract exhibited a strong antioxidant power with an IC50 value of 1.37 mg/mL. Insight into the results obtained, C. colocynthis seed extract may be used as a promising weapon to fight against cancer and free radicals’ damage.

Withania frutescens (W. frutescens) is a medicinal plant that is largely used in the Morrocan pharmacopeia for disease treatment. This work was conducted to investigate the chemical characterization, analgesic, anti-inflammatory, and healing activities of W. frutescens. The chemical characterization of W. frutescens extract was done using HPLC; the anti-inflammatory test was performed with doses 300, 400 and 450 mg/kg, and the healing activity was assessed using two creams (extract 5% and extract 10%). Phytochemical analysis revealed the presence of phenolic compounds. The results of the anti-inflammatory test were more pronounced when compared with the reference drug with a maximum inhibition percentage of 82.20% ± 8.69 obtained at the dose of 450 mg/kg. Local application of 10% plant cream induced 80.17% ± 7.89 of inflammation inhibition when compared with the indomethacin drug 92.33% ± 11.27. The studied plant extract showed a promising healing activity with the following percentage: 99.03% ± 0.76 (extract 10%), 98.61% ± 1.91 (extract 5%), and 57.43% ± 2.97 (control); meanwhile, the value reached to 100% ± 0.02 for the drug that was used as a reference within the first 2 weeks. The plant studied in this work would be a promising source for conceptualizing effective drugs against inflammatory diseases.

Barbary fig called prickly pear is a plant belonging to family Cactaceae growing under hard climate conditions. A spiny variety of prickly pear named “Drbana” (Opuntia megacantha) and two non-spiny varieties named “Akria” and “Mlez” (Opuntia ficus-indica) growing in the Rhamna region (Morocco) were studied in terms of physicochemical characteristics. The physicochemical characterization (humidity, water activity, pH, total titratable acidity, Brix, and ash content) and the biochemical characterization (total carotenoid content, betalain content, total polyphenolic content, and ascorbic acid content) of the fruit pulp of prickly pear were performed according to the previously reported methods. The finding of physicochemical characterization of all studied varieties showed that the fruit pulp also contained an interesting bioactive compound classes in humidity, water activity, pH, total titratable acidity, Brix, and ash content. Regarding the biochemical characterization, the obtained finding showed the fruit pulp also contained an interesting bioactive compound classes particularly the total betalains, polyphenols, carotenoids, and ascorbic acids. Based on the obtained results in the current research work, we can affirm that the fruits of all studied varieties meet the requirement for being exploited in food, cosmetic, and pharmaceutical industries.

This study was performed to investigate the phytochemical profile, and the, in vitro, and, in silico, antioxidant and antibacterial properties of the essential oil (EO) extracted from Origanum compactum. EO phytochemical screening was examined by gas chromatography coupled to mass spectrometry. The antioxidant potential, in vitro, was assessed using reducing power(FRAP), free 2,2 diphenylpicrylhydrazyl (DPPH) radical scavenging and total antioxidant capacity tests. Antibacterial properties against two Gram (−) and two Gram (+) bacteria were assessed using the minimal inhibitory concentration (MIC) and the disc diffusion methods. By use of molecular docking, antioxidant and antibacterial activities of oregano EO were also tested. Thymol (75.53%) was the major compound among the nine compounds identified in the EO of Origanum compactum, followed by carvacrol (18.26%). Oregano EO showed an important antioxidant capacity, as tested by FRAP and DPPH assays, with EC50 and IC50 values of 13.300 ± 0.200 and 0.690 ± 0.062 mg/mL, respectively. The same EO has a total antioxidant capacity of 173.900 ± 7.231 mg AAE/g EO. The antibacterial results showed significant activity of Origanum compactum EO against all tested bacteria, especially against S. aureus (MIC = 0.25 mg/mL) and B. subtilis (MIC = 0.06 mg/mL). In silico, carvacrol was the most active molecule against nicotinamide adenine dinucleotide phosphate oxidase (2CDU) and S. aureus nucleoside diphosphate kinase (3Q8U) with a glide score of −6.082, and −6.039 kcal/mol, respectively. Regarding the inhibition of E. coli beta-ketoacyl-[acyl carrier protein] synthase (1FJ4), piperitenone was the most active molecule with a glide score of −7.112 kcal/mol. In light of the results obtained, the EO of Origanum compactum Moroccan species can be used as promising natural food conservatives and an agent to fight antibiotic-resistant nosocomial microbes.

To investigate the phytochemical composition, acute and sub-acute toxicity of the aqueous extract of B. dioica roots. The phytochemical analysis was performed using gas chromatography-mass spectrometry (GC-MS). The acute toxicity of the aqueous extract of B.dioica roots was assessed in mice with single doses ranging from 250 to 1000 mg/kg for 14 days. The sub-acute toxicity was carried out with repeated doses ranging from 64.5 to 250 mg/kg for 28 days. Histopathological changes and markers of renal and liver function were investigated. The results of GC-MS analysis showed the presence of interesting phytoconstituents. The clinical symptoms and mortalities that occurred in treated mice were more remarkable due to the increasing sample concentration of the studied extract. However, no mortalities, or histopathological, or biochemical disturbances were observed even at the maximal dose administered (250 mg/kg). The outcome of the present work suggests that the treatment of animals with single doses of B. dioica roots extract higher than 250 mg/kg produces significant toxicities, however, treatment with repeated doses up to 250 mg/kg for 28 days seems to be safe for animals.

Effervescent formulation helps in faster and better absorption of drugs, especially those that are rapidly soluble in water. However, these tablets require special packaging in order to prevent them from absorbing moisture, hence increasing cost. We compared an effervescent tablet prepared using an in-house developed method (multi-layer tablet with acid and base part separated by an inert layer) to a European effervescent tablet (Efferalgan®) in a single-center, randomized cross-over study among twelve healthy volunteers. Blood samples were collected for 8 h and analyzed for paracetamol concentration using HPLC. Our results showed that both the products have similar pharmacokinetic profiles with no significant difference observed for C last , T half , K elim , and MRT (p-value > 0.05). Moreover, to assess bioequivalence we did not find any significant difference (p-value > 0.05) in AUC (27.12 ± 6.02 vs. 27.29 ± 2.64 µg.h/ml), C max (7.42 ± 1.06 vs. 7.83 ± 1.19 µg/ml) and t max (0.85 ± 0.22 vs. 0.83 ± 0.25 h). The TR ratios for AUC, C max , and t max were 0.99, 0.95, and 1.02 respectively, and were all within the specified FDA limits i.e., 0.8-1.25. We found our test tablet to be bioequivalent to that of Efferalgan®., (© 2024. The Author(s).)

Iron homeostasis is vital for normal physiology, but in the majority of circumstances, like iron overload, this equilibrium is upset leading to free iron in the plasma. This condition with excess iron is known as hemochromatosis, which has been linked to many side effects, including cancer and liver cirrhosis. The current research aimed to investigate active molecules from Streptomyces sp. isolated from the extreme environment of Bahawalpur deserts. The strain was characterized using 16 S rRNA sequencing. Chemical analysis of the ethyl acetate cure extract revealed the presence of phenols, flavonoids, alkaloids, and tannins. Multiple ultraviolet (UV) active metabolites that were essential for the stated pharmacological activities were also demonstrated by thin layer chromatography (TLC) and high-performance liquid chromatography (HPLC). Additionally, Gas chromatography/mass spectrometry (GC-MS) analysis revealed the primary constituents of the extract to compose of phenol and ester compounds. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay was used to assess the extract's antioxidant capacity, and the results showed a good half-maximal inhibitory concentration (IC 50 ) value of 0.034 µg/mL in comparison to the positive control ascorbic acid's 0.12 µg/mL. In addition, iron chelation activity of extract showed significant chelation potential at 250 and 125 µg/mL, while 62.5 µg/mL showed only mild chelation of the ferrous ion using ethylene diamine tetra acetic acid (EDTA) as a positive control. Likewise, the extract's cytotoxicity was analyzed through 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay using varying concentrations of the extract and showed 51% cytotoxicity at 350 µg/mL and 65% inhibition of cell growth at 700 µg/mL, respectively. The bioactive compounds from Streptomyces sp. demonstrated strong antioxidant and iron chelating potentials and can prolong the cell survival in extreme environment., (© 2024. The Author(s).)

Fluorescent Carbon Quantum Dots (CQDs) are being used in medical applications, particularly in theranostics. These Carbon Quantum Dots have been gaining more attention lately due to their potential as an effective replacement for hazardous synthetic organic dyes in a variety of biomedical applications, including live cell imaging and diagnostics. In this study, highly fluorescent Carbon Quantum Dots by one pot microwave based green route with a size of less than 10 nm, was prepared from commercially available almond resin, Prunus dulcis and conjugated with honey as additional reagent for surface functionalization. They exhibit a deep blue emission on excitation at 350 nm with an elevated quantum yield at 61%. They possess atomic nature and basic features such as high photo-stability, varying fluorescence, greater biocompatibility, and better water solubility. These fluorescent labels exhibit faster cellular invagination without disturbing the cell stability. The CQDs present cell imaging capacity with multi-coloration for visualizing the fine architecture of the nucleus naming, the nuclear membrane and nucleolus, which is linked with their varied, surface structures such as amphiphilic property and higher positive charges. These characteristics with minimal invasion have made carbon quantum dots to become the spotlight in theranostics. They can be used as alternatives to synthetic dyes for fluorescence- related cell-imaging. The intriguing fact about this approach is that it opens the possibility of combining therapy and diagnostics into one unit, which can alter how some diseases are handled and, in turn, transform the field of healthcare., (© 2024. The Author(s).)

In the present work, phytoconstituents from Citrus limon are computationally tested against SARS-CoV-2 target protein such as Mpro - (5R82.pdb), Spike - (6YZ5.pdb) &RdRp - (7BTF.pdb) for COVID-19. Docking was done by glide model, QikProp was performed by in silico ADMET screening & Prime MM-GB/SA modules were used to define binding energy. When compared with approved COVID-19 drugs such as Remdesivir, Ritonavir, Lopinavir, and Hydroxychloroquine, plant-based constituents such as Quercetin, Rutoside, Naringin, Eriocitrin, and Hesperidin. bind with significant G-scores to the active SARS-CoV-2 place. The constituents Rutoside and Eriocitrin were studied in each MD simulation in 100 ns against 3 proteins 5R82.pdb, 6YZ5.pdb and 7BTF.pdb.We performed an assay with significant natural compounds from contacts and in silico results (Rutin, Eriocitrin, Naringin, Hesperidin) using 3CL protease assay kit (B.11529 Omicron variant). This kit contained 3CL inhibitor GC376 as Control. The IC 50 value of the test compound was found to be Rutin -17.50 μM, Eriocitrin-37.91 μM, Naringin-39.58 μM, Hesperidine-140.20 μM, the standard inhibitory concentration of GC376 was 38.64 μM. The phytoconstituents showed important interactions with SARS-CoV-2 targets, and potential modifications could be beneficial for future development., (© 2024 The Authors. ChemistryOpen published by Wiley-VCH GmbH.)

The present study deals with the production of cellulase-free endoxylanase by Aspergillus niger ISL-9 using wheat bran as a solid substrate. Endoxylanase was produced under a solid-state fermentation. Various growth parameters were optimized for the improved production of the enzyme. The Substrate level of 15 g was optimized as it provided the fungus with balanced aeration and nutrition. Among the six moisture contents investigated, Moisture Content 5 (MC5) was optimized (g/l: malt extract, 10; (NH 4 ) 2 HPO 4 , 2.5; urea, 1.0) and 10 mL of MC5 was found to give the highest production of endoxylanase. The pH and time of incubation were optimized to 6.2 and 48 h respectively. The Inoculum size of 2 mL (1.4 × 10 6 spores/mL) gave the maximum enzyme production. After optimization of these growth parameters, a significantly high endoxylanase activity of 21.87 U/g was achieved. Very negligible Carboxymethylcellulase (CMCase) activity was observed indicating the production of cellulase-free endoxylanase. The notable finding is that the endoxylanase activity was increased by 1.4-fold under optimized conditions (p ≤ 0.05). The overall comparison of kinetic parameters for enhanced production of endoxylanase by A. niger ISL-9 under Solid State Fermentation (SSF) was also studied. Different kinetic variables which included specific growth rate, product yield coefficients, volumetric rates and specific rates were observed at 48, 72 and 96 h incubation time and were compared for MC1 and MC5. Among the kinetic parameters, the most significant result was obtained with volumetric rate constant for product formation (Q p ) that was found to be optimum (1.89 U/h) at 72 h incubation period and a high value of Q p i.e.1.68 U/h was also observed at 48 h incubation period. Thus, the study demonstrates a cost-effective and environmentally sustainable process for xylanase production and exhibits scope towards successful industrial applications., (© 2024. The Author(s).)

Introduction: This research aims to explore the molecular composition, antioxidant capabilities, and antibacterial effects of the essential oils from Tetraclinis articulateata and Juniperus phoenicea ., Methods: Essential oils were extracted using hydrodistillation. Gas chromatography combined with mass spectrometry was used to determine the chemical makeup of essential oils. Two methods are used to assess the antioxidant activity of essential oils: the reduction of iron (ferric reducing antioxidant power or frap) and the trapping of the free radical 2,2-Diphenyl-1-Picrylhydrazyl (DPPH). The antimicrobial potential of essential oils was assessed using the diffusion method on a solid-state disk in comparison to nine bacterial and seven fungal souches., Results and Discussion: The essential oil yields from Tetraclinis articulata and Juniperus phoenicea are 0.46% ± 0.02% and 0.83% ± 0.05%, respectively. According to CG/SM's chromatographic analyses, the predominant constituent in the essential oil of J. Phoenicea is α-pinène (59.51%), while the main constituents in the essential oil of T. Articulata ? are Bornyle acetate (18.91%) and camphor (28.48%). The assessment of antioxidant activities reveals intriguing antioxidant qualities in the essential oils of the species under investigation. T. Articulata essential oils yield the greatest results in the DPPH and FRAP tests, with CI50 values of around 266.9 ± 5.4 μg/mL and EC50 values of 433.16 ± 4.13 μg/mL, respectively. Except for Staphylococcus epidermidis, Staphylococcus aureus BLACT, and Pseudomonas aeroginosa, the two essential oils have demonstrated significant bactericidal activity against all bacterial and fungal souches (MIC <2 mg/mL et MBC <3.5 mg/mL). The inhibiting effect of these oils on bacterial and fungal development raises potential application areas in the food, cosmetic, and pharmaceutical industries. In addition, the current study investigated the potential antifungal, antibacterial, and antioxidant activities of the essential oils from Juniperus phoenicea and Tetraclinis articulate plants via the Glide molecular docking methodology, and most of these constituents were observed to be potent therapeutic agents., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Asbabou, Hanane, Gourich, Siddique, Drioiche, Remok, Saidi, Adadi, Khamar, Almaary, Mekonnen, Bourhia, Bouzoubaa and Zair.)

The objective of this study was to explore how watermelon rinds (WMRs) and their derivatives, specifically water-soluble polysaccharides (WMRPs) and hemicellulose (WMRH), as sources of dietary fiber, could enhance the quality of wheat bread. The extraction process yielded 34.4% for WMRP and 8.22% for WMRH. WMR, WMRP, and WMRH exhibited promising functional characteristics and were incorporated separately into wheat flour with low bread-making quality (FLBM) at varying proportions (0.5%, 1%, and 1.5% ( w / w )). The volume, texture, and crust and crumb color underwent evaluation and were compared to the control. The findings indicated that incorporating WMR notably enhanced the alveograph profile of the dough, demonstrating a more effective impact than the addition of WMRP and WMRH. Adding WMR, WMRP, and WMRH at a 1% concentration to low-quality wheat flour for bread making increased the deformation work values by 16%, 15%, and 13%, respectively, and raised the P/L ratios by 42%, 36%, and 38%, respectively. Additionally, the assessment of the bread highlighted a substantial enhancement in both volume and texture profile when WMR was added, in contrast to the control bread (made with FLBM). These findings underscore that incorporating 1% WMR into FLBM was the most effective means of improving bread quality based on the results of this study.

We present a new selective Metamaterial Perfect Absorber (MPA) consisting of zinc oxide embedded silver (Ag@ZnO), designed for applications in infrared stealth technology. The numerical simulation included a wide frequency range from 1 to 1000 THz and shows that the design MPA structure presented two absorption peaks at the desired wavelengths of 1.7 µm and 6.5 µm. The absorptivity of both peaks reached approximately 93.1% and 93.5%. The first peak at 1.7 µm decreases the scattering of IR laser beams from the surface of the MPA structure and also lowers the infrared tracks that could direct laser-guided devices to its specific target. On the other hand, the second peak reduces the surface heat wave. The suggested MPA (Ag@ZnO) structure is activated by a plane wave using a full wave vector and a broad frequency domain solution. In the framework of computer simulation technology (CST) Microwave Studio, uses both Finite-Difference-Time-Domain (FDTD) and Finite-Element-Method (FEM) techniques to predict the optical behavior of the proposed MPA structure. Both peaks achieved a high value of absorptivity due to the simultaneous excitation of the electric and magnetic dipole at resonance wavelength., (© 2024. The Author(s).)

Monkeypox virus (MPV) infection has developed into a re-emerging disease, and despite the potential of tecovirimat and cidofovir drugs, there is currently no conclusive treatment. The treatment's effectiveness and cost challenges motivate us to use In Silico approaches to seek natural compounds as candidate antiviral inhibitors. Using Maestro 11.5 in Schrodinger suite 2018, available natural molecules with validated chemical structures collected from Eximed Laboratory were subjected to molecular docking and ADMET analysis against the highly conserved A42R Profilin-like Protein of Monkeypox Virus Zaire-96-I-16 (PDB: 4QWO) with resolution of 1.52 Å solved 3D structure. Compared to the FDA-approved Tecovirimat, molecular docking revealed that Salsoline derivatives, Genistein, Semisynthetic derivative of kojic acid, and Naringenin had strengthened affinity (-8.9 to -10 kcal/mol) to 4QWO, and the molecular dynamic's simulation confirmed their high binding stability. In support of these results, the hydrogen bond analysis indicated that the Salsoline derivative had the most robust interaction with the binding pockets of 4QWO among the four molecules. Moreover, the comparative free energy analyses using MM-PBSA revealed an average binding free energy of the complexes of Salsoline derivative, Genistein, Semisynthetic derivative of kojic acid, Naringenin, of -106.418, -46.808, -50.770, and -63.319 kJ/mol, respectively which are lower than -33.855 kJ/mol of the Tecovirimat complex. Interestingly, these results and the ADMET predictions suggest that the four compounds are promising inhibitors of 4QWO, which agrees with previous results showing their antiviral activities against other viruses., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chebaibi, Bourhia, Amrati, Slighoua, Mssillou, Aboul-Soud, Khalid, Hassani, Bousta, Achour, Benhida and Daoud.)

Endocrine-disrupting chemicals (EDCs) are substances that can disrupt the normal functioning of hormones.Using aptamers, which are biological recognition elements, biosensors can quickly and accurately detect EDCs in environmental samples. However, the elucidation of aptamer structures by conventional methods is highly challenging due to their complexity. This has led to the development of three-dimensional aptamer structures based on different models and techniques. To do this, we developed a way to predict the 3D structures of the SS DNA needed for this sequence by starting with an aptamer sequence that has biosensor properties specific to bisphenol-A (BPA), one of the chemicals found in water samples that can interfere with hormones. In addition, we will elucidate the intermolecular mechanisms and binding affinity between aptamers and endocrine disruptors using bioinformatics techniques such as molecular docking, molecular dynamics simulation, and binding energies. The outcomes of our study are to compare modeling programs and force fields to see how reliable they are and how well they agree with results found in the existing literature, to understand the intermolecular mechanisms and affinity of aptamer-based biosensors, and to find a new way to make aptamers that takes less time and costs less., Competing Interests: Declaration of Competing interest The authors declare no conflict of interest, financial or otherwise., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Present study assessed the growth of two plant species and ion uptake by them grown on different proportion of industrial solid waste and garden soil. The industrial waste having high concentration of chemicals were used with garden soil at different proportion i.e. 0% (T0), 5% (T1), 10% (T2), 15% (T3) and 20% (T4). Two species namely Conocarpus erectus (alien plant) and Dodonaea viscosa (indigenous) were used as test plants in pot study. Different parameters including growth, physiology, and anatomy of plants and concentration of cations (Na + , K + , Ca 2+ , and Mg 2+ ) in the plant shoot and root were measured at different time duration (initial, 1 st , 2 nd , 3 rd and 4 th month). The key objective of the study was to use these plants to establish their plantations on the barren lands where industrial solid wastes were being disposed of. C. erectus showed better growth than D. viscosa, as well as more uptake of ions. A significant increase in plant growth was observed in fourth month in T1, where plant height reached 24.5% and 46% for C. erectus and D. viscosa, respectively. At harvest, in C. erectus, no significant difference in the fresh (65-78 g) and dry weight (24-30 g) of the shoot was observed across treatments compared to the control. In D. viscosa, at the time of harvest, the fresh and dry weights of the root and shoot showed a strong, significantly decreasing pattern across T1, T2, and T3, leading to the death of the plant at T3 and T4. Further, optimum ratio of waste soil to garden soil was found as 10:90 and 20:80 to establish the plantations of D. viscosa and C. erectus, respectively in areas where such solid waste from industries are disposed. Findings can be used for the restoration of such solid waste for the sustainable management of industrial areas and their associated ecosystems., (© 2024. The Author(s).)

In this work, we sought to validate the use of Euphorbia calyptrata (L.), a Saharan and Mediterranean medicinal plant, in traditional pharmacopeia. GC-MS/MS identified volatile compounds of potential therapeutic interest. Antioxidant tests were performed using β-carotene decolorization, DPPH radical scavenging, FRAP, beta-carotene bleaching, and TAC. The antimicrobial activity was evaluated on solid and liquid media for bacterial and fungal strains to determine the zone of inhibition and the minimum growth concentration (MIC) of the microbes tested. The hemolytic activity of these essential oils was assessed on red blood cells isolated from rat blood. Phytochemical characterization of the terpenic compounds by GC-MS/MS revealed 31 compounds, with alpha-Pinene dominating (35.96 %). The antioxidant power of the essential oils tested revealed an IC 50 of 67.28 μg/mL (DPPH), EC 50 of 80.25.08±1.42 μg/mL (FRAP), 94.83±2.11 μg/mL (beta carotene) and 985.07±0.70 μg/mL (TAC). Evaluating solid media's antibacterial and antifungal properties revealed a zone of inhibition between 10.28 mm and 25.80 mm and 31.48 and 34.21 mm, respectively. On liquid media, the MIC ranged from 10.27 μg/mL to 24.91 μg/mL for bacterial strains and from 9.32 μg/mL to 19.08 μg/mL for fungal strains. In molecular docking analysis, the compounds naphthalene, shogunal, and manol oxide showed the greatest activity against NADPH oxidase, with Glide G scores of -5.294, -5.218 and -5.161 kcal/mol, respectively. For antibacterial activity against E. coli beta-ketoacyl-[acyl carrier protein] synthase, the most potent molecules were cis-Calamenene, alpha.-Muurolene and Terpineol, with Glide G-scores of -6.804, -6.424 and -6.313 kcal/mol, respectively. Hemolytic activity revealed a final inhibition of 9.42±0.33 % for a 100 μg/mL concentration. The essential oils tested have good antioxidant, antimicrobial, and hemolytic properties thanks to their rich phytochemical composition, and molecular docking analysis confirmed their biological potency., (© 2024 The Authors. ChemistryOpen published by Wiley-VCH GmbH.)

Imidacloprid (IMI) is one of the top-notch insecticides that adversely affects the body organs including the liver. Malvidin (MAL) is a natural flavonoid which exhibits a wide range of pharmacological properties. This research was designed to evaluate the protective ability of MAL to counteract IMI instigated liver toxicity in rats. Thirty-two rats were divided into four groups including control, IMI (5mg/kg), IMI (5mg/kg) + MAL (10mg/kg) and MAL (10mg/kg) alone treated group. The recommended dosages were administrated through oral gavage for 4 weeks. It was revealed that IMI intoxication disrupted the PI3K/AKT and Nrf-2/Keap-1 pathway. Furthermore, the activities of catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), heme-oxygenase-1 (OH-1) and glutathione reductase (GSR) were reduced while upregulating reactive oxygen species (ROS) and malondialdehyde (MDA) levels after IMI treatment. Moreover, IMI poisoning increased the levels of ALT (Alanine aminotransferase), AST (Aspartate transaminase), and ALP (Alkaline phosphatase) while reducing the levels of total proteins and albumin in hepatic tissues of rats. Besides, IMI administration escalated the expressions of Bcl-2-associated protein x (Bax) and cysteine-aspartic acid protease-3 (Caspase-3) while downregulating the expressions of B-cell lymphoma 2 (Bcl-2). Similarly, IMI intoxication, increased the levels of Interleukin-6 (IL-6), Nuclear factor kappa-B (NF-κB), Interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and the activity of cyclooxygenase-2 (COX-2). Furthermore, IMI disrupted the normal architecture of hepatic tissues. However, MAL treatment remarkably protected the liver tissues via regulating abovementioned disruptions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The distribution and composition of the vegetation are greatly affected by the edaphology and topography of an area. The current study explores the vegetation structure of the herbaceous layer at various habitats of district Kohat for the first time. A survey was conducted during the spring seasons of 2021, 2022 and 2023 selecting 40 sites on the basis of edaphology, topography, altitude, aspect and status. Data was collected via quadrat approach to establish plant communities by species Importance Value (IV), point out dominant species by Total IV (TIV) and dominant families via Total Family IV (TFIV). The quantitative biological spectrum was also calculated. Communities' phytosociological characteristics were analyzed via various diversity indices (Shannon's Index (H), Simpson's Index (D), Species Richness (SR), Evenness (E) and Maturity index (Mi)) while similarity between the communities was calculated by using Sorensen's Index. The findings revealed a total of 253 species belonging to 57 families having the dominant species Cynodon dactylon (L.) Pers. (TIV, 484.3) followed by Saussuria heteromalla (D. Don) Hand. (TIV, 360.4), Anagallis arvensis L. (TIV, 353.2) and Aristida adscensionis L. (TIV, 349.65). Among 40 plant communities, Poaceae (TFIV, 2706.6), Asteraceae (TFIV, 2018.8), Fabaceae (TFIV, 1071.5) and Brassicaceae (TFIV, 825.9) were the dominant families. Therophytes (TIV, 7882) class was the dominant life form class followed by hemicryptophytes (TIV, 2517) while microphylls (TIV, 4669) class was the dominant leaf size class followed by nanophylls (TIV, 5469). Environmental factors i.e. topography and edaphic characteristics, showed significant effects on the diversity of the communities. The study concludes in a diverse pattern of distribution with a rich flora in the area warranting its documentation which will preserve the valuable species opening vistas for future research., (© 2024. The Author(s).)

The study was designed to explore the corrosion prevention capabilities of Citrullus colocynthis seeds alkaloid-rich extract (CSEA) on MS in a 1 M HCl environment by use of electrochemical and theoretical methods. Notably, Electrochemical Impedance Spectroscopy (EIS) and potentiodynamic polarization were used to probe the impact of immersion time and temperature. Energy-dispersive X-ray spectroscopy (EDX) and spanning electron microscopy (SEM) were used to confirm the presence of a protective layer on the substrate surface. Density functional theory (DFT) method was used to optimize the investigated species by use of B3LYP/6-31 + G(d, p) level of theory. The global and local quantum chemical reactivity descriptors were calculated to explore the inhibition corrosion efficiency and to identify the most favorable sites for electrophilic and nucleophilic attacks. Monte Carlo (MC) and molecular dynamics simulation (MDS) methods were used to study the interactions between corrosion inhibitor and metal surface. Noteworthy, results showed that CSEA exhibited an impressive inhibition efficiency, which reached 94.3% with a concentration of 2 g/L at 298 K. Potentiodynamic polarization revealed that the extract acted as a mixed-type inhibitor. Nyquist graphs showed that charge-transfer resistance and dæouble-layer capacitance both rised with increasing CSEA concentration, suggesting better inhibition efficiency. Notably, the Langmuir adsorption isotherm is well-aligned with the adsorption of inhibitor compounds. Importantly, all aforementioned theoretical methods were in agreement with the experimental findings. The outcome of the present work supported using Citrullus colocynthis seeds alkaloid-rich extract as ecofriendly agents to prevent corrosion., (© 2024. The Author(s).)

Coxiella burnetii, the causative agent of Q fever, is an intracellular pathogen posing a significant global public health threat. There is a pressing need for dependable and effective treatments, alongside an urgency for further research into the molecular characterization of its genome. Within the genomic landscape of Coxiella burnetii, numerous hypothetical proteins remain unidentified, underscoring the necessity for in-depth study. In this study, we conducted comprehensive in silico analyses to identify and prioritize potential hypothetical protein of Coxiella burnetii, aiming to elucidate the structure and function of uncharacterized protein. Furthermore, we delved into the physicochemical properties, localization, and molecular dynamics and simulations, and assessed the primary, secondary, and tertiary structures employing a variety of bioinformatics tools. The in-silico analysis revealed that the uncharacterized protein contains a conserved Mth938-like domain, suggesting a role in preadipocyte differentiation and adipogenesis. Subcellular localization predictions indicated its presence in the cytoplasm, implicating a significant role in cellular processes. Virtual screening identified ligands with high binding affinities, suggesting the protein's potential as a drug target against Q fever. Molecular dynamics simulations confirmed the stability of these complexes, indicating their therapeutic relevance. The findings provide a structural and functional overview of an uncharacterized protein from C. burnetii, implicating it in adipogenesis. This study underscores the power of in-silico approaches in uncovering the biological roles of uncharacterized proteins and facilitating the discovery of new therapeutic strategies. The findings provide valuable preliminary data for further investigation into the protein's role in adipogenesis., (© 2024. The Author(s).)

The available Epstein Barr virus vaccine has tirelessly harnessed the gp350 glycoprotein as its target epitope, but the result has not been preventive. Right here, we designed a global multi-epitope vaccine for EBV; with special attention to making sure all strains and preventive antigens are covered. Using a robust computational vaccine design approach, our proposed vaccine is armed with 6-16 mers linear B-cell epitopes, 4-9 mer CTL epitopes, and 8-15 mer HTL epitopes which are verified to induce interleukin 4, 10 & IFN-gamma. We employed deep computational mining coupled with expert intelligence in designing the vaccine, using human Beta defensin-3-which has been reported to induce the same TLRs as EBV-as the adjuvant. The tendency of the vaccine to cause autoimmune disorder is quenched by the assurance that the construct contains no EBNA-1 homolog. The protein vaccine construct exhibited excellent physicochemical attributes such as Aliphatic index 59.55 and GRAVY - 0.710; and a ProsaWeb Z score of - 3.04. Further computational analysis revealed the vaccine docked favorably with EBV indicted TLR 1, 2, 4 & 9 with satisfactory interaction patterns. With global coverage of 85.75% and the stable molecular dynamics result obtained for the best two interactions, we are optimistic that our nontoxic, non-allergenic multi-epitope vaccine will help to ameliorate the EBV-associated diseases-which include various malignancies, tumors, and cancers-preventively., (© 2024. The Author(s).)

This study used conservative one variable-at-a-time study and statistical surface response methods to increase the yields of an extracellular thermostable protease secreted by a newly identified thermophilic Bacillus subtilis BSP strain. Using conventional optimization techniques, physical parameters in submerged fermentation were adjusted at the shake flask level to reach 184 U/mL. These physicochemical parameters were further optimized by statistical surface response methodology using Box Behnken design, and the protease yield increased to 295 U/mL. The protease was purified and characterized biochemically. Both Ca 2+ and Fe 2+ increased the activity of the 36 kDa protease enzyme. Based on its strong inhibition by ethylenediaminetetracetate (EDTA), the enzyme was confirmed to be a metalloprotease. The protease was also resistant to various organic solvents (benzene, ethanol, methanol), surfactants (Triton X-100), sodium dodecyl sulfate (SDS), Tween 20, Tween-80 and oxidants hydrogen per oxide (H 2 O 2 ). Characteristics, such as tolerance to high SDS and H 2 O 2 concentrations, indicate that this protease has potential applications in the pharmaceutical and detergent industries., (© 2024. The Author(s).)

Understanding the distribution of the plant species of an unexplored area is the utmost need of the present-day. In order to collect vegetation data, Quadrat method was used having size of 1 m 2 . The composite soil samples from each site were tested for various edaphic properties. PC-ORD v.5 was used for the classification of the vegetation while CANOCO v.5.1 was used for ordination of the data and to find out the complex relationship between plants and environment. Survey was conducted during summer season and a total of 216 herbaceous species were recorded from forty different sites of District Kohat, Pakistan. Cluster Analysis (CA) and Two-Way Cluster Analysis (TWCA) classified the vegetation of forty sites into six major plant groups i.e., 1. Paspalum paspalodes, Alternanthera sessilis, Typha domingensis, 2. Cynodon dactylon, Parthenium hysterophorus, Brachiaria ramosa, 3. Cynodon dactylon, Eragrostis minor, Cymbopogon jwarancusa, 4. Cymbopogon jwarancusa, Aristida adscensionis, Boerhavia procumbens, 5. Cymbopogon jwarancusa, Aristida adscensionis, Pennisetum orientale and 6. Heteropogon contortus, Bothriochloa ischaemum, Chrysopogon serrulatus. They were named after the dominant species based on their Importance Value (IV). The detrended correspondence analysis (DCA) analysis further confirmed the vegetation classification. Canonical correspondence analysis (CCA) indicated that the species distribution in the area was strongly affected by various environmental factors including status, soil characteristics, topography and altitude., (© 2024. The Author(s).)

This work examines the capacity of Naringin and Rutin to influence the DNA damage response (DDR) pathway by investigating their interactions with key DDR proteins, including PARP-1, ATM, ATR, CHK1, and WEE1. Through a combination of in silico molecular docking and in vitro evaluations, we investigated the cytotoxic and genotoxic effects of these compounds on MDA-MB-231 cells, comparing them to normal human fibroblast cells (2DD) and quiescent fibroblast cells (QFC). The research found that Naringin and Rutin had strong affinities for DDR pathway proteins, indicating their capacity to specifically regulate DDR pathways in cancer cells. Both compounds exhibited preferential cytotoxicity towards cancer cells while preserving the vitality of normal 2DD fibroblast cells, as demonstrated by cytotoxicity experiments conducted at a dose of 10 µM. The comet experiments performed particularly on QFC cells provide valuable information on the genotoxic impact of Naringin and Rutin, highlighting the targeted initiation of DNA damage in cancer cells. The need to use precise cell models to appropriately evaluate toxicity and genotoxicity is emphasized by this discrepancy. In addition, ADMET and drug-likeness investigations have emphasized the pharmacological potential of these compounds; however, they have also pointed out the necessity for optimization to improve their therapeutic profiles. The antioxidant capabilities of Naringin and Rutin were assessed using DPPH and free radical scavenging assays at a concentration of 10 µM. The results confirmed that both compounds have a role in reducing oxidative stress, hence enhancing their anticancer effects. Overall, Naringin and Rutin show potential as medicines for modulating the DDR in cancer treatment. They exhibit selective toxicity towards cancer cells while sparing normal cells and possess strong antioxidant properties. This analysis enhances our understanding of the therapeutic uses of natural chemicals in cancer treatment, supporting the need for more research on their mechanisms of action and clinical effectiveness., (© 2024. The Author(s).)

The purpose of this study was to evaluate the vitamin D status and determine the factors influencing it in the Drâa-Tafilalet community (southeastern Morocco). Sociodemographic factors, health, cognitive status, sun exposure, and nutritional conditions were examined to help us understand their association with vitamin D status. Vitamin D data were gathered through laboratory testing, while demographic and health information was collected through interviews with participants in 2023. The study involved 100 participants aged 60 and above, most of whom were women (85%) rather than men (15%). The majority of participants were Arabs (90%), with a minority being Amazigh (10%). The average vitamin D level was 31.83 ± 10.55 ng/mL, varying based on participants' age, education, and gender. Sun-exposed individuals exhibited significantly higher mean vitamin D levels (33.56 ± 11.99 ng/mL) compared to those with limited sun exposure (28.97 ± 9.28 ng/mL). Moreover, the time spent outdoors, seasonal changes, and the duration of sun exposure affected the levels of vitamin D. These findings depict the vitamin D status of the elderly population of Drâa-Tafilalet, recognized as one of Morocco's poorest regions, shedding light on the significant influencers. Nonetheless, additional research is necessary to explore the correlation between dietary habits, sunlight exposure, and vitamin D levels in both young and elderly populations.