Voltammetric Label‐free Immunosensors for the Diagnosis of Cystic Echinococcosis

Cystic echinococcosis (CE) or hydatid disease is a parasitic infection caused by Echinococcus granulosus. Early serodiagnosis and continuous monitoring of the disease is very important for medical treatment. Here, we report the detecting of both echinococcus antigen and antibody for the diagnosis of hydatid disease using square wave voltammetry (SWV)‐based immunosensors. The gold electrodes were functionalized using cysteamine/phenylene diisothiocyanate linkers and used for the immunosensors fabrication. The hydatid antigen and antibody immunosensors were constructed by the immobilization of either purified rabbit polyclonal antibody or recombinant antigen B (AgB), respectively on the functionalized gold electrodes surfaces. The detection in both cases was achieved by following the change in the SWV reduction peak current of the ferro/ferricyanide redox couple upon antibody or antigen binding. These immunosensors enabled the detection of echinococcus antigen and antibody within a concentration range of 1 pg.mL^?1 to 1 μg.mL^?1 with detection limits of 0.4 pg.mL^?1 and 0.3 pg.mL^?1, respectively. A preliminary application of the developed immunosensor was performed in spiked serum sample showing good recovery percentages ranging from 102 to 110 % for both hydatid antibody and antigen detection. This easy‐to‐use, sensitive, and low cost quantitative method holds great promise for the early diagnosis of hydatid disease and thus, better managements and treatment outcomes.     

In Vivo Imaging of the Tumor‐Associated Enzyme NCEH1 with a Covalent PET Probe

Herein, we report the development of an ¹⁸F‐labeled, activity‐based small‐molecule probe targeting the cancer‐associated serine hydrolase NCEH1. We undertook a focused medicinal chemistry campaign to simultaneously preserve potent and specific NCEH1 labeling in live cells and animals, while permitting facile ¹⁸F radionuclide incorporation required for PET imaging. The resulting molecule, [¹⁸F]JW199, labels active NCEH1 in live cells at nanomolar concentrations and greater than 1000‐fold selectivity relative to other serine hydrolases. [¹⁸F]JW199 displays rapid, NCEH1‐dependent accumulation in mouse tissues. Finally, we demonstrate that [¹⁸F]JW199 labels aggressive cancer tumor cells in vivo, which uncovered localized NCEH1 activity at the leading edge of triple‐negative breast cancer tumors, suggesting roles for NCEH1 in tumor aggressiveness and metastasis.     

Two new zinc(II) and mercury(II) complexes based on N,N′‐(cyclohexane‐1,2‐diylidene)bis(4‐fluorobenzohydrazide): synthesis,crystal structures and antibacterial activities

Reaction of N,N′‐(cyclohexane‐1,2‐diylidene)bis(4‐fluorobenzohydrazide), C₂₀H₁₈F₂N₄O₂, ( L^F ), with zinc chloride and mercury(II) chloride produced different types and shapes of neutral coordination complexes, namely, dichlorido[N,N′‐(cyclohexane‐1,2‐diylidene)bis(4‐fluorobenzohydrazide)‐κ²N,O]zinc(II), [ZnCl₂(C₂₀H₁₈F₂N₄O₂)], ( 1 ), and dichlorido[N,N′‐(cyclohexane‐1,2‐diylidene)bis(4‐fluorobenzohydrazide)‐κ⁴O,N,N′,O′]mercury(II), [HgCl₂(C₂₀H₁₈F₂N₄O₂)], ( 2 ). The organic ligand and its metal complexes are characterized using various techniques: IR, UV–Vis and nuclear magnetic resonance (NMR) spectroscopies, in addition to powder X‐ray diffraction (PXRD), single‐crystal X‐ray crystallography and microelemental analysis. Depending upon the data from these analyses and measurements, a typical tetrahedral geometry was confirmed for zinc complex ( 1 ), in which the Zn^II atom is located outside the bis(benzhydrazone) core. The Hg^II atom in ( 2 ) is found within the core and has a common octahedral structure. The in vitro antibacterial activities of the prepared compounds were evaluated against two different bacterial strains, i.e. gram positive Bacillus subtilis and gram negative Pseudomonas aeruginosa bacteria. The prepared compounds exhibited differentiated growth‐inhibitory activities against these two bacterial strains based on the difference in their lipophilic nature and structural features.     

Development of Sustained Release Baricitinib Loaded Lipid-Polymer Hybrid Nanoparticles with Improved Oral Bioavailability

Baricitinib (BTB) is an orally administered Janus kinase inhibitor, therapeutically used for the treatment of rheumatoid arthritis. Recently it has also been approved for the treatment of COVID-19 infection. In this study, four different BTB-loaded lipids (stearin)-polymer (Poly(d,l-lactide-co-glycolide)) hybrid nanoparticles (B-PLN1 to B-PLN4) were prepared by the single-step nanoprecipitation method. Next, they were characterised in terms of physicochemical properties such as particle size, zeta potential (ζP), polydispersity index (PDI), entrapment efficiency (EE) and drug loading (DL). Based on preliminary evaluation, the B-PLN4 was regarded as the optimised formulation with particle size (272 ± 7.6 nm), PDI (0.225), ζP (−36.5 ± 3.1 mV), %EE (71.6 ± 1.5%) and %DL (2.87 ± 0.42%). This formulation (B-PLN4) was further assessed concerning morphology, in vitro release, and in vivo pharmacokinetic studies in rats. The in vitro release profile exhibited a sustained release pattern well-fitted by the Korsmeyer–Peppas kinetic model (R² = 0.879). The in vivo pharmacokinetic data showed an enhancement (2.92 times more) in bioavailability in comparison to the normal suspension of pure BTB. These data concluded that the formulated lipid-polymer hybrid nanoparticles could be a promising drug delivery option to enhance the bioavailability of BTB. Overall, this study provides a scientific basis for future studies on the entrapment efficiency of lipid-polymer hybrid systems as promising carriers for overcoming pharmacokinetic limitations.     

A Narrative Review on the Phytochemistry,Pharmacology and Therapeutic Potentials of Clinacanthus nutans (Burm. f.) Lindau Leaves as an Alternative Source of Future Medicine

The application of natural products and supplements has expanded tremendously over the past few decades. Clinacanthus nutans (C. nutans), which is affiliated to the Acanthaceae family, has recently caught the interest of researchers from the countries of subtropical Asia due to its medicinal uses in alternative treatment for skin infection conditions due to insect bites, microorganism infections and cancer, as well as for health well-being. A number of bioactive compounds from this plant’s extract, namely phenolic compounds, sulphur containing compounds, sulphur containing glycosides compounds, terpens-tripenoids, terpens-phytosterols and chlorophyll-related compounds possess high antioxidant activities. This literature search yielded about one hundred articles which were then further documented, including the valuable data and findings obtained from all accessible electronic searches and library databases. The promising pharmacological activities from C. nutans leaves extract, including antioxidant, anti-cancer, anti-viral, anti-bacterial, anti-fungal, anti-venom, analgesic and anti-nociceptive properties were meticulously dissected. Moreover, the authors also discuss a few of the pharmacological aspect of C. nutans leaves extracts against anti-hyperlipidemia, vasorelaxation and renoprotective activities, which are seldom available from the previously discussed review papers. From the aspect of toxicological studies, controversial findings have been reported in both in-vitro and in-vivo experiments. Thus, further investigations on their phytochemical compounds and their mode of action showing pharmacological activities are required to fully grasp both traditional usage and their suitability for future drugs development. Data related to therapeutic activity and the constituents of C. nutans leaves were searched by using the search engines Google scholar, PubMed, Scopus and Science Direct, and accepting literature reported between 2010 to present. On the whole, this review paper compiles all the available contemporary data from this subtropical herb on its phytochemistry and pharmacological activities with a view towards garnering further interest in exploring its use in cardiovascular and renal diseases.     

Characterization of the Phytochemical Composition and Bioactivities of Anacyclus maroccanus Ball. and Anacyclus radiatus Loisel Aerial Parts: Preliminary Evidence for the Possible Development of Moroccan Plants

In the present study, the phytochemical composition and bioactivities of A. maroccanus (AM) and A. radiatus (AR), two ecotypes collected in the Demnate road and Essaouira regions, respectively, were studied to highlight a pharmacological interest and to enable possible pharmaceutical development. To this end, methanolic and ethyl acetate extracts were prepared for each ecotype by fractionation; next, their phytochemical composition was evaluated by spectrophotometric and chromatographic analysis. Moreover, in line with the available evidence for Anacyclus spp. and their traditional use, a screening of bioactivities, including antioxidant, hypoglycemic, antiglycative, chelating, and antibacterial activities, was performed. The extracts were characterized by high amounts of polyphenols, tannins, and flavonoids, especially in the methanolic extracts; these samples were also enriched in carotenoids despite a lower chlorophyll content. Chlorogenic acid and rutin were the major identified compounds. The extracts also showed interesting hypoglycemic, antiglycative, and antibacterial properties, although with differences in efficacy and potency. Present results provide more scientific basis to the ethnopharmacological uses of Anacyclus spp. and suggest a further interest in AM and AR ecotypes as natural sources of bioactive compounds and/or phytocomplexes for possible pharmaceutical and nutraceutical developments.     

In memory of Professor Ali H. Nayfeh

Nonlinear Dynamics - In this paper, we propose and numerically study a nonlinear, asymmetric, passive metamaterial that achieves giant non-reciprocity with (i) broadband frequency operation and...     

Multiple rogue wave and solitary solutions for the generalized BK equation via Hirota bilinear and SIVP schemes arising in fluid mechanics

The multiple lump solutions method is employed for the purpose of obtaining multiple soliton solutions for the generalized Bogoyavlensky-Konopelchenko(BK) equation. The solutions obtained contain first-order, second-order, and third-order wave solutions. At the critical point,the second-order derivative and Hessian matrix for only one point is investigated, and the lump solution has one maximum value. He's semi-inverse variational principle(SIVP) is also used for the generalized BK equation. Three major cases are studied, based on two different ansatzes using the SIVP. The physical phenomena of the multiple soliton solutions thus obtained are then analyzed and demonstrated in the figures below, using a selection of suitable parameter values.This method should prove extremely useful for further studies of attractive physical phenomena in the fields of heat transfer, fluid dynamics, etc.     

Antimicrobial and Antioxidant Properties of Total Polyphenols of Anchusa italica Retz

Anchusa italica Retz has been used for a long time in phytotherapy. The aim of the present study was to determine the antioxidant and antibacterial activities of extracts from the leaves and roots of Anchusa italica Retz. We first determined the content of phenolic compounds and flavonoids using Folin–Ciocalteu reagents and aluminum chloride (AlCl₃). The antioxidant activity was determined using three methods: reducing power (FRAP), 2.2-diphenyl-1-picrylhydrazyl (DPPH), total antioxidant capacity (TAC). The antimicrobial activity was investigated against four strains of Escherichia coli, two strains of Klebsiella pneumoniae and coagulase-negative Staphylococcus, and one fungal strain of Candida albicans. The results showed that the root extract was rich in polyphenols (43.29 mg GAE/g extract), while the leave extract was rich in flavonoids (28.88 mg QE/g extract). The FRAP assay showed a strong iron reduction capacity for the root extract (IC₅₀ of 0.11 µg/mL) in comparison to ascorbic acid (IC₅₀ of 0.121 µg/mL). The DPPH test determined an IC₅₀ of 0.11 µg/mL for the root extract and an IC₅₀ of 0.14 µg/mL for the leaf extract. These values are low compared to those for ascorbic acid (IC₅₀ of 0.16 µg/mL) and BHT (IC₅₀ 0.20 µg/mL). The TAC values of the leaf and root extracts were 0.51 and 0.98 mg AAE/g extract, respectively. In vitro, the extract showed inhibitory activity against all strains studied, with diameters of zones of inhibition in the range of 11.00–16.00 mm for the root extract and 11.67–14.33 mm for the leaf extract. The minimum inhibitory concentration was recorded for the leaf extract against E. coli (ATB:57), corresponding to 5 mg/mL. Overall, this research indicates that the extracts of Anchusa italica Retz roots and leaves exert significant antioxidant and antibacterial activities, probably because of the high content of flavonoids and polyphenols.