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This study reported the fabrication and characterization of gastric dressing, composed of gelatine (GEL), chitosan (CH), and pomegranate peel (PP) extract. The structural changes occurring after γ-irradiation of GEL–CH–PP dressing were reported. The results showed that the electron paramagnetic resonance (EPR) spectroscopy of un-irradiated GEL–CH–PP showed two paramagnetic centers, which corresponded to g = 2.19 and g = 2.002. After irradiation, a new active centre appeared at g = 2.0035 at 10 kGy. The Fourier transform infrared spectroscopy (FTIR) analyses revealed an increase in peak intensity at C–H chains, as well as the C=O carboxyl groups at 10 kGy, due to the cross-linking phenomenon. The X-ray diffraction analysis showed a low change of crystallinity between the range of 2θ (15–30°). Moreover, γ-rays enhanced scavenging DPPH radical activity (51±%) and chelating power activities 79.12%. A significant inhibition of antibacterial and anti-biofilm activities (p < 0.01) was noticed. The hemolysis rates showed 0.42%, suggesting a high hemocompatibility, and exhibited significant anti-inflammatory activity in vitro (48%). In vivo, the healing effects of GEL–CH–PP dressing showed that the incidence and severity of gastric histopathological lesions decreased, compared with the ulcerated group, which could explain the bioavailability and the pharmacokinetic findings. The results highlight the loading of bioactive agents into polymer-based gastric dressings, with promising pharmacokinetics properties and effects on the induced ulcera in rabbits. [ABSTRACT FROM AUTHOR]

Ducrosia flabellifolia Boiss. is a rare desert plant known to be a promising source of bioactive compounds. In this paper, we report for the first time the phytochemical composition and biological activities of D. flabellifolia hydroalcoholic extract by using liquid chromatography–electrospray tandem mass spectrometry (ESI-MS/MS) technique. The results obtained showed the richness of the tested extract in phenols, tannins, and flavonoids. Twenty-three phytoconstituents were identified, represented mainly by chlorogenic acid, followed by ferulic acid, caffeic acid, and sinapic acid. The tested hydroalcoholic extract was able to inhibit the growth of all tested bacteria and yeast on agar Petri dishes at 3 mg/disc with mean growth inhibition zone ranging from 8.00 ± 0.00 mm for Enterococcus cloacae (E. cloacae) to 36.33 ± 0.58 mm for Staphylococcus epidermidis. Minimal inhibitory concentration ranged from 12.5 mg/mL to 200 mg/mL and the hydroalcoholic extract from D. flabellifolia exhibited a bacteriostatic and fungistatic character. In addition, D. flabellifolia hydroalcoholic extract possessed a good ability to scavenge different free radicals as compared to standard molecules. Molecular docking studies on the identified phyto-compounds in bacterial, fungal, and human peroxiredoxin 5 receptors were performed to corroborate the in vitro results, which revealed good binding profiles on the examined protein targets. A standard atomistic 100 ns dynamic simulation investigation was used to further evaluate the interaction stability of the promising phytocompounds, and the results showed conformational stability in the binding cavity. The obtained results highlighted the medicinal use of D. flabellifolia as source of bioactive compounds, as antioxidant, antibacterial, and antifungal agent. [ABSTRACT FROM AUTHOR]

This study investigated the druggability, pharmacokinetics and ethyl acetate extract of Teucrium polium (EA T. polium) and the protective effect against carbon tetrachloride (CCl4) induced liver cirrhosis in rats. The total antioxidant capacity (TAC) and scavenging activity of the extract were examined. The in vivo protective study was based on the use of an animal model of CCl4-induced liver cirrhosis. Four groups of rats have been used: Group I: control rats; Group II: received CCl4 in olive oil (0.5 mL/kg); Group III: received the EA T. polium (25 mg/kg) of pretreatment for seven days by gavage then CCl4 in olive oil by gavage for 15 days. Group IV: received the EA of T. polium for seven days (25 mg/kg). EA T. polium was found to possess significant antioxidant capacity. CCl4 caused a hepatotoxicity associated increase in both levels of AST and ALT, which were reduced back to normal values following EA T. polium pretreatment. Hepatotoxicity associated structural modifications of liver tissues and increase in thiobarbituric acid reactive substances (TBARS), conjugated dienes (CD) and carbonyl proteins (CP), associated decreases in several assessed antioxidant enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT). The in vivo findings on the protective effect of T. polium were supported by its druggability, its pharmacokinetic properties and molecular docking assays. These results confirm the modulatory antioxidant and hepatoprotective potential of T. polium in this experimental liver cirrhosis model. T. polium phytochemicals are good candidates for further pharmaceutical explorations and drug design. [ABSTRACT FROM AUTHOR]

For decades, mass drug treatment with praziquantel (PZQ) has been utilized to treat schistosomiasis, yet reinfection and the risk of drug resistance are among the various factors precluding successful elimination of schistosomiasis. Tractable models that replicate "real world" field conditions are crucial to effectively evaluate putative schistosomiasis vaccines. Herein, we describe the cellular immune responses and cytokine expression profiles under field conditions that include prior infection with schistosomes followed by treatment with PZQ. Baboons were exposed to Schistosoma mansoni cercariae through trickle infection over 5 weeks, allowed for chronic disease to develop, and then treated with PZQ. Peripheral blood mononuclear cells (PBMCs) were monitored for cellular immune response(s) at each disease stage and PZQ therapy. After initial infection and during chronic disease, there was an increase in non-classical monocytes, NK and NKT cells while the CD4:CD8 T cell ratio inverted from a 2:1 to 1:2.5. The cytokine expressions of PBMCs after trickle infections were polarized more toward a Th2 response with a gradual increase in Th1 cytokine expression at chronic disease stage. Following PZQ treatment, with the exception of an increase in B cells, immune cell populations reverted back toward naïve levels; however, expression of almost all Th1, Th2, and Th17 cytokines was significantly increased. This preliminary study is the first to follow the cellular immune response and cytokine expression profiles in a non-human primate model simulating field conditions of schistosomiasis and PZQ therapy, providing a promising reference in predicting the immune response to future vaccines for schistosomiasis. [ABSTRACT FROM AUTHOR]

Sm-p80, the large subunit of Schistosoma mansoni calpain, is a leading candidate for a schistosomiasis vaccine. The prophylactic and antifecundity efficacy of Sm-p80 has been tested in three animal models (mouse, hamster and baboon) using a multitude of vaccine formulations and approaches. In our continual effort to enhance the vaccine efficacy, in this study, we have utilized the adjuvant, synthetic hexa-acylated lipid A derivative, glucopyranosyl lipid A (GLA) formulated in aluminum (GLA-Alum) with recombinant Sm-p80. The rSm-p80+GLA-Alum immunization regimen provided 33.33%-53.13% reduction in worm burden in the mouse model and 38% worm burden reduction in vaccinated baboons. Robust Sm-p80-specific immunoglobulin (Ig)G, IgG1, IgG2a and IgM responses were observed in all immunized animals. The rSm-p80+GLA-Alum coadministration induced a mix of T-helper (Th) cells (Th1, Th2 and Th17) responses as determined via the release of interleukin (IL)-2, IL-4, IL-18, IL-21, IL-22 and interferon-γ. [ABSTRACT FROM AUTHOR]

Abstract: Sm‐p80‐based vaccine efficacy for Schistosoma mansoni was evaluated in a baboon model of infection and disease. The study was designed to replicate a human vaccine implementation scenario for endemic regions in which vaccine would be administered following drug treatment of infected individuals. In our study, the Sm‐p80‐based vaccine reduced principal pathology producing hepatic egg burdens by 38.0% and egg load in small and large intestines by 72.2% and 49.4%, respectively, in baboons. Notably, hatching rates of eggs recovered from liver and small and large intestine of vaccinated animals were significantly reduced, by 60.4%, 48.6%, and 82.3%, respectively. Observed reduction in egg maturation/hatching rates was supported by immunofluorescence and confocal microscopy showing unique differences in Sm‐p80 expression in worms of both sexes and matured eggs. Vaccinated baboons had a 64.5% reduction in urine schistosome circulating anodic antigen, a parameter that reflects worm numbers/health status in infected hosts. Preliminary analyses of RNA sequencing revealed unique genes and canonical pathways associated with establishment of chronic disease, praziquantel‐mediated parasite killing, and Sm‐p80‐mediated protection in vaccinated baboons. Overall, our study demonstrated efficacy of the Sm‐p80 vaccine and provides insight into some of the epistatic interactions associated with protection. [ABSTRACT FROM AUTHOR]

Abstract: Schistosomiasis is of public health importance to an estimated one billion people in 79 countries. A vaccine is urgently needed. Here, we report the results of four independent, double‐blind studies of an Sm‐p80‐based vaccine in baboons. The vaccine exhibited potent prophylactic efficacy against transmission of Schistosoma mansoni infection and was associated with significantly less egg‐induced pathology, compared with unvaccinated control animals. Specifically, the vaccine resulted in a 93.45% reduction of pathology‐producing female worms and significantly resolved the major clinical manifestations of hepatic/intestinal schistosomiasis by reducing the tissue egg‐load by 89.95%. A 35‐fold decrease in fecal egg excretion in vaccinated animals, combined with an 81.51% reduction in hatching of eggs into the snail‐infective stage (miracidia), demonstrates the parasite transmission‐blocking potential of the vaccine. Substantially higher Sm‐p80 expression in female worms and Sm‐p80‐specific antibodies in vaccinated baboons appear to play an important role in vaccine‐mediated protection. Preliminary analyses of RNA sequencing revealed distinct molecular signatures of vaccine‐induced effects in baboon immune effector cells. This study provides comprehensive evidence for the effectiveness of an Sm‐p80‐based vaccine for schistosomiasis. [ABSTRACT FROM AUTHOR]

The synthesis, X-ray single crystal, and optical properties of a novel sulfate-bridged copper complex have been investigated. Moreover, the biological activities of our complex were explored for the development of both antioxidant and anti-tumoral drugs. [Display omitted] • Single crystals of a novel sulfate-bridged complex were grown by the slow evaporation method. • Its structure self-organizes in μ 2 -SO 4 cross-linked 1D infinite chains that are further implicated in hydrogen bonding engendering a 3D supramolecular network. • Thermal analyses pointed out the high thermal stability of our complex. • Optical measurements highlight the presence of a hypsochromic shift in the absorption and photoluminescence spectra. • The biochemical and histological studies invigorated further analyses of our complex for the development of both antioxidant and anti-tumoral drugs. A sulfate-bridged complex [Cu(µ 2 -SO 4)(Im) 4 ] (1) was prepared and structurally characterized, where Im: imidazole. The X-ray structure analysis reveals that 1 crystallizes in the monoclinic system with space group C2/c. The octahedral coordination around the metal center is made up of four distinct imine nitrogen atoms in the equatorial plane, and two sulfate oxygen atoms occupying the axial sites. The covalent linkage between metals via the sulfate group, forming infinite 1D zigzag chains, ensures the entanglement of the structure. These chains, in turn, are further assembled into a 2D network through N H⋯O hydrogen bonding. Thermal analyses underline the high thermal stability of our complex, which starts to decompose at 200 °C. The infrared spectrum confirms the results obtained from the crystallographic analysis. Optical studies reveal the presence of a hypsochromic effect noticed in the absorption and photoluminescence spectra. The synthesized compound was found to reduce both oxidative injury and histopathological features, which are associated with skeletal metastases as a result of malignant Walker 256/B breast cancer cells. [ABSTRACT FROM AUTHOR]

Primaquine ( PQ) is the only drug used to prevent relapse of malaria due to P. vivax and P. ovale, by eradicating the dormant liver form of the parasite (hypnozoites). The side-effects associated with PQ limits is uses in treatment of malaria. To overcome the premature oxidative deamination and to increase the life span of drug in the biological system, the novel glyco-conjugates of PQ were synthesized by coupling of primaquine with hexoses in phosphate buffer. The saccharide part of the hybrid molecules thought to direct the drug to the liver, where hypnozoites resides. All the synthesized compounds were fully characterized and evaluated for their radical curative activities. The three compounds viz glucoside ( 15a), galactoside ( 15b) and mannoside ( 15c) with high activity were tested for their activity in rhesus monkeys where the most active compound 15b showed twofold activity (100% radical curative activity at 1.92 mmol/kg) than the standard drug PQ diphosphate (3.861 mmol/kg). It is proposed that results from these studies may be advantageous to develop a new potent tissue schizonticide antimalarial compound. [ABSTRACT FROM AUTHOR]

Polycyclic aromatic hydrocarbons (PAHs) are toxic for humans and marine fauna alike. The current study assessed the impact of PAHs on the migratory behaviour of meiobenthic nematodes collected from the Bizerte lagoon, Tunisia. The experiment lasted for 15 days and was carried in open microcosms, which comprised a lower, contaminated and an upper, uncontaminated compartment. Three treatments were used, for each of them an untreated control was set up: sediment contaminated with chrysene (116 ng g−1 dry weight (DW), with phenanthrene (116 ng g−1 DW) and a mixture of both. The results showed a significant decrease in diversty and abundance in the lower, contaminated compartments compared to the upper zones. The results also highlighted that under an increased stress some species progressively increased in number, these were considered PAH-tolerant species such as Odontophora villoti , some others had an occasionally increased in number were considered as opportunistic species, such as Paracomesoma dubium and the species that showed a progressive decreased in number, such as Metoncholaimus pristiurus and Steineria sp., Terschellingia. longicaudata , and Oncholaimellus sp. were classified as PAH-sensitive. Moreover, an increase in the activity of biochemical biomarkers was observed following the exposure of males and gravid females of T. longicaudata to 29, 58 and 87 ng g−1 DW of chrysene and phenanthrene paralleled by a higher vulnerability of the latter demographic category. Besides, a significant decrease in fertility of females and an increase in pharyngeal sucking power were observed for both types of PAHs considered. The sex ratio was also significantly imbalanced in the favor of males, which suggest that chrysene and phenanthrene affect also the hormone system of T. longicaudata. The high affinities of these PAHs and their molecular interactions with both germ line development protein 3 (GLD-3) and sex-determining protein (SDP) may justify these results and explain the toxicokinetic attributes. [Display omitted] • Abundance and diversity decreased in presence of phenanthrene and/or chrysene. • Odontophora villoti and Paracomesoma dubium proved to be tolerant nematode taxa. • Potential antagonistic interaction was found between phenanthrene and chrysene. • Biomarkers, relative growth, and demographic traits represented reliable indicators. [ABSTRACT FROM AUTHOR]

Fighting against the emergent coronavirus disease (COVID-19) remains a big challenge at the front of the world communities. Recent research has outlined the potential of various medicinal herbs to counteract the infection. This study aimed to evaluate the interaction of artemisinin, a sesquiterpene lactone extracted from the Artemisia genus, and its derivatives with the SARS-CoV-2 main protease. To assess their potential use against COVID-19, the interactions of the main active principle of Artemisia with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro) was investigated through in silico probing. Our results showed that artemesinin and its derivatives manifested good oral absorption and bioavailability scores (0.55). They potently bound to the Mpro site of action—specifically, to its Cys145 residue. The selected compounds established two to three conventional hydrogen bonds with binding affinities ranging between −5.2 and −8.1 kcal/mol. Furthermore, artemisinin interactions with angiotensin converting enzyme 2 (ACE2) were dependent on the ACE2 allelic variants. The best score was recorded with rs961360700. A molecular dynamic simulation showed sufficient stability of the artemisinin–Mpro complex on the trajectory of 100 ns simulation frame. These binding interactions, together with drug-likeness and pharmacokinetic findings, confirmed that artemisinin might inhibit Mpro activity and explain the ethnopharmacological use of the herb and its possible antiviral activity against SARS-CoV-2 infection inducing COVID-19. Nevertheless, it interacted differently with the various ACE2 allelic variants reported to bind with the SARS-CoV-2 spike protein. [ABSTRACT FROM AUTHOR]

In this study, the antioxidant and anti-inflammatory effects of Zingiber officinale roscoe and Allium subhirsutum aqueous extracts were examined in a carrageenan-induced acute inflammation model. Some markers of inflammation such as hematological parameters, fibrinogen and C-reactive protein were measured. Variables reflecting oxidative stress included thiobarbituric acid reactive substances (TBARS), advanced oxidation of protein products (AOPP), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione were determined in both inflamed foci and erythrocytes. The in silico molecular docking simulation showed that the main components of Zingiber officinale roscoe and Allium subhirsutum bound to toll-like receptor 6 (TLR6) with high affinities. Moreover, histological examinations of paw edema were carried out. Both Zingiber officinale roscoe and Allium subhirsutum ameliorated the induced inflammation and oxidative stress status as outlined by anti-edematous, antioxidant and anti-inflammatory activities. Our investigation lends pharmacological support to the medical uses of these spices in the management of inflammatory disorders and oxidative damage. The results of the in silico assay satisfactory explain the in vivo effects as compared with indomethacin. [ABSTRACT FROM AUTHOR]