Isolation and Characterization of Werneria Chromene and Dihydroxyacidissimol from Burkillanthus malaccensis (Ridl.) Swingle

The secondary metabolites of endemic plants from the Rutaceae family, such as Burkillanthusmalaccensis (Ridl.) Swingle from the rainforest of Malaysia, has not been studied. Burkillanthusmalaccensis (Ridl.) Swingle may produce antibacterial and antibiotic-potentiating secondary metabolites. Hexane, chloroform, and methanol extracts of leaves, bark, wood, pericarps, and endocarps were tested against bacteria by broth microdilution assay and their antibiotic-potentiating activities. Chromatographic separations of hexane extracts of seeds were conducted to investigate effective phytochemicals and their antibacterial activities. Molecular docking studies of werneria chromene and dihydroxyacidissiminol against SARS-CoV-2 virus infection were conducted using AutoDock Vina. The methanol extract of bark inhibited the growth of Staphylococcusaureus, Escherichiacoli, and Pseudomonasaeruginosa with the minimum inhibitory concentration of 250, 500, and 250 µg/mL, respectively. The chloroform extract of endocarps potentiated the activity of imipenem against imipenem-resistant Acinetobacterbaumannii. The hexane extract of seeds increased the sensitivity of P. aeruginosa against ciprofloxacin and levofloxacin. The hexane extract of seeds and chloroform extract of endocarps were chromatographed, yielding werneria chromene and dihydroxyacidissiminol. Werneria chromene was bacteriostatic for P.aeruginosa and P.putida, with MIC/MBC values of 1000 > 1000 µg/mL. Dihydroxyacidissiminol showed the predicted binding energies of −8.1, −7.6, −7.0, and −7.5 kcal/mol with cathepsin L, nsp13 helicase, SARS-CoV-2 main protease, and SARS-CoV-2 spike protein receptor-binding domain S-RBD. Burkillanthusmalaccensis (Ridl.) Swingle can be a potential source of natural products with antibiotic-potentiating activity and that are anti-SARS-CoV-2.

Drug Delivery Strategies and Biomedical Significance of Hydrogels: Translational Considerations.

Hydrogels are a promising and attractive option as polymeric gel networks, which have immensely fascinated researchers across the globe because of their outstanding characteristics such as elevated swellability, the permeability of oxygen at a high rate, good biocompatibility, easy loading, and drug release. Hydrogels have been extensively used for several purposes in the biomedical sector using versatile polymers of synthetic and natural origin. This review focuses on functional polymeric materials for the fabrication of hydrogels, evaluation of different parameters of biocompatibility and stability, and their application as carriers for drugs delivery, tissue engineering and other therapeutic purposes. The outcome of various studies on the use of hydrogels in different segments and how they have been appropriately altered in numerous ways to attain the desired targeted delivery of therapeutic agents is summarized. Patents and clinical trials conducted on hydrogel-based products, along with scale-up translation, are also mentioned in detail. Finally, the potential of the hydrogel in the biomedical sector is discussed, along with its further possibilities for improvement for the development of sophisticated smart hydrogels with pivotal biomedical functions.

Toxoplasma gondii Infection in Marine Animal Species, as a Potential Source of Food Contamination: A Systematic Review and Meta-Analysis.

PURPOSE: Many marine animals are infected and susceptible to toxoplasmosis, which is considered as a potential transmission source of Toxoplasma gondii to other hosts, especially humans. The current systematic review and meta-analysis aimed to determine the prevalence of T. gondii infection among sea animal species worldwide and highlight the existing gaps. METHODS: Data collection was systematically done through searching databases, including PubMed, Science Direct, Google Scholar, Scopus, and Web of Science from 1997 to July 2020. RESULTS: Our search strategy resulted in the retrieval of 55 eligible studies reporting the prevalence of marine T. gondii infection. The highest prevalence belonged to mustelids (sea otter) with 54.8% (95% CI 34.21-74.57) and cetaceans (whale, dolphin, and porpoise) with 30.92% (95% CI 17.85-45.76). The microscopic agglutination test (MAT) with 41 records and indirect immunofluorescence assay (IFA) with 30 records were the most applied diagnostic techniques for T. gondii detection in marine species. CONCLUSIONS: Our results indicated the geographic distribution and spectrum of infected marine species with T. gondii in different parts of the world. The spread of T. gondii among marine animals can affect the health of humans and other animals; in addition, it is possible that marine mammals act as sentinels of environmental contamination, especially the parasites by consuming water or prey species.

Targeting Acanthamoeba proteins interaction with flavonoids of Propolis extract by in vitro and in silico studies for promising therapeutic effects.

Background : Propolis is a natural resinous mixture produced by bees. It provides beneficial effects on human health in the treatment/management of many diseases. The present study was performed to demonstrate the anti- Acanthamoeba activity of ethanolic extracts of Propolis samples from Iran. The interactions of the compounds and essential proteins of Acanthamoeba were also visualized through docking simulation. Methods: The minimal inhibitory concentrations (MICs) of Propolis extract against Acanthamoeba trophozoites and cysts was determined in vitro. In addition, two-fold dilutions of each of agents were tested for encystment, excystment and adhesion inhibitions. Three major compounds of Propolis extract such as chrysin, tectochrysin and pinocembrin have been selected in molecular docking approach to predict the compounds that might be responsible for encystment, excystment and adhesion inhibitions of A. castellanii. Furthermore, to confirm the docking results, molecular dynamics (MD) simulations were also carried out for the most promising two ligand-pocket complexes from docking studies. Results : The minimal inhibitory concentrations (MICs) 62.5 and 125 µg/mL of the most active Propolis extract were assessed in trophozoites stage of Acanthamoeba castellanii ATCC30010 and ATCC50739, respectively. At concentrations lower than their MICs values (1/16 MIC), Propolis extract revealed inhibition of encystation. However, at 1/2 MIC, it showed a potential inhibition of excystation and anti-adhesion. The molecular docking and dynamic simulation revealed the potential capability of Pinocembrin to form hydrogen bonds with A. castellanii Sir2 family protein (AcSir2), an encystation protein of high relevance for this process in Acanthamoeba. Conclusions : The results provided a candidate for the development of therapeutic drugs against Acanthamoeba infection. In vivo experiments and clinical trials are necessary to support this claim.

Quercetin and/or Ascorbic Acid Modulatory Effect on Phenobarbital-Induced Sleeping Mice Possibly through GABAA and GABAB Receptor Interaction Pathway.

Depressive disorder is a recurrent illness that affects large numbers of the general population worldwide. In recent years, the goal of depression treatment has moved from symptomatic response to that of full remission. However, treatment-resistant depression is a major challenge in the treatment of depression or depression-related disorders. Consensus opinion, therefore, suggests that effective combined aggressive initial treatment is the most appropriate strategy. This study aimed to evaluate the effects of quercetin (QUR) and/or ascorbic acid (AA) on Phenobarbital-induced sleeping mice. QUR (50 mg/kg) and/or AA (25 mg/kg) with or without intraperitoneally pre-treated with GABA receptor agonist (diazepam: 2 mg/kg, i.p.) or antagonist (Flumazenil: 2.5 mg/kg, i.p.) to underscore the effects, as well as the possible involvement of the GABA receptor in the modulatory action of QUR and AA in sleeping mice. Additionally, an in silico study was undertaken to predict the involvement of GABA receptors in the sleep mechanism. Findings suggest that the pretreatment of QUR and AA modulated the onset and duration of action of the standard drugs in experimental animals. The acute administration of QUR and/or AA significantly (p < 0.05) reversed the DZP-mediated onset of action and slightly reversed the duration of sleep time in comparison to the vehicle (control) group. A further combination of QUR or AA with the FLU resulted in an enhancement of the onset of action while reducing the duration of action, suggesting a FLU-like effect on the test animals. In in silico studies, AA and QUR showed good to moderate binding affinities with GABAA and GABAB receptors. Both QUR and AA produced a stimulatory-like effect on mice, possibly through the GABAA and GABAB receptor interaction pathways. Further studies are necessary to verify this activity and clarify the exact mechanism of action(s) involved.

Scolicidal and Apoptotic Activities of 5-hydroxy-1, 4-naphthoquinone as a Potent Agent against Echinococcus granulosus Protoscoleces.

Cystic hydatid disease (CHD) is a zoonotic disease with different clinical stages caused by the larval stage of the cestode Echinococcus granulosus. It is important to highlight as a public health problem in various regions of the world. In the current study, the efficacy and apoptotic activity of the liposomal system containing juglone (5-hydroxy-1,4-naphthoquinone) were assessed against protoscoleces (PSCs) in vitro. To this aim, firstly, liposomal vesicles were prepared by the thin-film method. Their physico-chemical features were assessed using Zeta-Sizer and Scanning Electron Microscope (SEM). Subsequently, various concentrations (50, 100, 200, 400, and 800 µg/mL) of juglone nanoliposomes at different exposure times (15, 30, 60, and 120 min) were used against PSCs. Results showed that juglone nanoliposomes at all tested concentrations induced scolicidal effect, however, 800 µg/mL and 400 µg/mL of juglone nanoliposomes could reach 100% mortality in 60 and 120 min, respectively. Additionally, we found that caspase-3 mRNA expression was higher in PSCs treated with juglone nanoliposomes compared to control groups (p < 0.001). Therefore, juglone nanoliposomes are suggested to have a more potent apoptotic effect on PSCs. Generally, optimized doses of juglone nanoliposomes could display significant scolicidal effects. Moreover, further in vivo studies are required to evaluate the efficacy of this nanoliposome.

Environmental and Health Hazards of Chromated Copper Arsenate-Treated Wood: A Review.

Copper chrome arsenate (CCA) water-borne solution used to be widely used to make timber highly resistant to pests and fungi, in particular, wood products designed for outdoor use. Nowadays, CCA is a restricted chemical product in most countries, since potential environmental and health risks were reported due to dermal contact with CCA residues from treated structures and the surrounding soil, as well as the contamination of soils. However, large quantities of CCA-treated timber are still in use in framings, outdoor playground equipment, landscaping, building poles, jetty piles, and fencing structures around the world, thus CCA remains a source of pollutants to the environment and of increasing toxic metal/metalloid exposure (mainly in children). International efforts have been dedicated to the treatment of materials impregnated with CCA, however not only does some reuse of CCA-treated timber still occur, but also existing structures are leaking the toxic compounds into the environment, with impacts on the environment and animal and human health. This study highlights CCA mechanisms and the documented consequences in vivo of its exposure, as well as the adverse environmental and health impacts.

Nerve-Cancer Cell Cross-talk: A Novel Promoter of Tumor Progression.

Recent studies have revealed the essential role played by nerves in tumor progression. Nerves have been shown to infiltrate the tumor microenvironment and actively stimulate cancer cell growth and dissemination. This mechanism involves the release of neurotransmitters, such as catecholamines and acetylcholine, directly into the vicinity of cancer and stromal cells to activate corresponding membrane receptors. Conversely, the secretion of neurotrophic growth factors by cancer cells drives the outgrowth of nerves in solid tumors. This reciprocal interaction between nerves and cancer cells provides new insights into the cellular and molecular bases of tumorigenesis and points to the potential utility of antineurogenic therapies. This review will discuss our evolving understanding of the cross-talk between nerves and cancer cells.