Grape pomace (GP) is a good source of high-value compounds as up to 60% of grape polyphenols remain in it after wine-making. To overcome traditional membrane technologies’ d rawbacks, such as fouling, a novel Zero Head Space extraction (ZHE) procedure was developed. The reaction vessel comprised a filtration device with a nitrocellulose membrane. The separation was performed at 50 lb/in2 and 23 °C, with no headspace during the process. Water and methanol (both acidifie d) were evaluated as solvents during two extraction stages for the recovery and fractionation of polyphenols. Aqueous extract (AE) was mainly constituted by monomeric polyphenols while Methanol extract (ME) presented less soluble compounds, as well as a higher concentration of total anthocyanin content than AE. Additional methanolic (CE) and acetone (CAE) extractions of residual GP showed CE presented a similar profile to ME (at a lower concentration), indicating ZHE efficiency at extracting polyphenols in GP. CAE presen... [more]

Translational medicine, the exchange between laboratory (bench) and the clinic (bedside), is decidedly taking on a vital role. Many companies are now focusing on a translational medicinal approach as a therapeutic strategy in decision making upon realizing the expenses of drug attrition in late-stage advancement. In addition, the utility of biomarkers in clinical decision and therapy guidance seeks to improve the patient outcomes and decrease wasteful and harmful treatment. Efficient biomarkers are crucial for the advancement of diagnoses, better molecular targeted therapy, along with therapeutic advantages in a broad spectrum of various diseases. Despite recent advances in the discovery of biomarkers, the advancement route to a clinically validated biomarker remains intensely challenging, and many of the candidate biomarkers do not progress to clinical applications, thereby widening the innovation gap between research and application. The present article will focus on the clinical vie... [more]

Human bone morphogenetic protein 2 (hBMP2) is routinely used in medical applications as an inducer of osteoformation. The recombinant production of BMP2 is typically performed using stable Chinese hamster ovary (CHO) cell lines. However, this process is inefficient, resulting in low product titers. In contrast, transient gene expression (TGE), which also enables the production of recombinant proteins, suffers from short production times and hence limited total product amounts. Here, we show that TGE-based BMP2 production is more efficient in HEKsus than in CHOsus cells. Independently of the cell lines, a bicistronic plasmid co-expressing EGFP and BMP2 facilitated the determination of the transfection efficiency but led to inferior BMP2 titers. Finally, we used a high cell density transient transfection (HCD-TGE) protocol to improve and extend the BMP2 expression by performing four rounds of serial transfections on one pool of HEKsus cells. This repeated transient transfection (RTT) pro... [more]

The ongoing pandemic of coronavirus disease (COVID-19) stimulated an unprecedented international collaborative effort for rapid diagnosis, epidemiologic surveillance, clinical management, prevention, and treatment. This review focuses on the current and new therapeutical approaches, summarizing the viral structure and life cycle, with an emphasis on the specific steps that can be interfered by antivirals: (a) inhibition of viral entry with anti-spike monoclonal antibodies; (b) inhibition of the RNA genome replication with nucleosidic analogs blocking the viral RNA polymerase; (c) inhibition of the main viral protease (Mpro), which directs the formation of the nonstructural proteins. An overview of the immunomodulatory drugs currently used for severe COVID-19 treatment and future therapeutical options are also discussed.

Oral antidiabetic drugs are usually costly and are associated with several adverse side effects. This has led to the use of medicinal plants that are considered to have multiple therapeutic targets and are readily accessible. In the Eastern Cape province of South Africa, the number of people using medicinal plants for the management of diabetes has been climbing steadily over the past two decades due to their cultural acceptability, accessibility, affordability, efficacy, and safety claims. In this study, a review of antidiabetic medicinal plants used in the Eastern Cape province of South Africa was conducted. A comprehensive literature survey was thoroughly reviewed using several scientific databases, ethnobotanical books, theses and dissertations. About forty-eight (48) plant species were identified as being used to treat diabetes by the people of Eastern Cape province. Among the plant species, only eight (8) species have not been scientifically evaluated for their antidiabetic activ... [more]

We propose a virtual screening method based on imbalanced data mining in this paper, which combines virtual screening techniques with imbalanced data classification methods to improve the traditional virtual screening process. First, in the actual virtual screening process, we apply k-means and smote heuristic oversampling method to deal with imbalanced data. Meanwhile, to enhance the accuracy of the virtual screening process, a particle swarm optimization algorithm is introduced to optimize the parameters of the support vector machine classifier, and the concept of ensemble learning is brought in. The classification technique based on particle swarm optimization, support vector machine and adaptive boosting is used to screen the molecular docking conformation to improve the accuracy of the prediction. Finally, in the experimental construction and analysis section, the proposed method was validated using relevant data from the protein data bank database and PubChem database. The experi... [more]

Bergenin is a phenolic glycoside that has been reported to occur naturally in several plant species, reported as a cardioprotective. However, bergenin, one of the important phytochemicals in these plants, is still not reported as a cardioprotective. The present study was designed to investigate the cardioprotective effects of bergenin on isoproterenol-induced myocardial infarction in rats. Bergenin and atenolol were administered through intraperitoneal (i.p.) injection to Sprague Dawley (SD) rats in separate experiments for five (5) days. At the end of this period, rats were administered isoproterenol (80 mg/kg s.c.) to induce myocardial injury. After induction, rats were anaesthetized to record lead II ECG, then sacrificed, blood was collected to analyze cardiac marker enzymes, and a histopathological study of the heart tissues was also performed. Pretreatment with bergenin showed a significant decrease in ST-segment elevation, deep Q-wave, infarct size, and also normalized cardiac ma... [more]

SARS-CoV-2, the virus that caused the widespread COVID-19 pandemic, is homologous to SARS-CoV. It would be ideal to develop antivirals effective against SARS-CoV-2. In this study, we chose one therapeutic target known as the main protease (Mpro) of SARS-CoV-2. A crystal structure (Id: 6LU7) from the protein data bank (PDB) was used to accomplish the screening and docking studies. A set of phytocompounds was used for the docking investigation. The nature of the interaction and the interacting residues indicated the molecular properties that are essential for significant affinity. Six compounds were selected, based on the docking as well as the MM-GBSA score. Pentagalloylglucose, Shephagenin, Isoacteoside, Isoquercitrin, Kappa-Carrageenan, and Dolabellin are the six compounds with the lowest binding energies (−12 to −8 kcal/mol) and show significant interactions with the target Mpro protein. The MMGBSA scores of these compounds are highly promising, and they should be investigated to det... [more]

Hibiscetin, as one of the main bioactive constituents of Hibiscus sabdariffa, has many pharmacological activities, but its antihyperglycemic activity has not been fully interpreted yet. The current research was developed from this perspective. The study intended to appraise the antidiabetic capability of hibiscetin in a high-fat diet (HFD) and streptozotocin (STZ; 50 mg/kg, intraperitoneally)-induced diabetes in an experimental animal. The efficiency of hibiscetin at 10 mg/kg in an “HFD/STZ model” remedy in rats with experimentally caused diabetes was explored for 42 days. The efficacy of hibiscetin was observed on several diabetes parameters. The average body weight and an array of biochemical markers were determined, including blood glucose, insulin, total protein (TP), lipid profile, aspartate aminotransferase (AST), alanine aminotransferase (ALT), IL-6, IL-1β, tumor necrosis factor-α (TNF-α), adiponectin, leptin, resistin, malondialdehyde (MDA), catalase (CAT), glutathione (GSH), a... [more]

(A. trifoliata) is a significant medicinal and edible fruit crop and has some important bioactivities. However, there are few studies on the bacteriostatic activity of A. trifoliata, and the underlying mechanism of A. trifoliata for antibacterial activity is still unknown. Therefore, the bacteriostatic activity and antibacterial mechanism of A. trifoliata were investigated by a combination of chemical assays, using the UHPLC-TOF-MS/MS technique. The results indicated that alkaloids, triterpenoids, and flavonoids are the major secondary bioactive compounds in A. trifoliata that play a crucial role in antibacterial activity. We found that EEPA exhibited both bacteriostatic and bactericidal effects against all Gram-positive and Gram-negative bacteria tested, with IZDs ranging from 13.80 ± 0.79 to 17.00 ± 0.58 mm. Significant differences in terms of sensitivity between Gram-positive and Gram-negative bacteria were not observed. In contrast, both antibiotics (kanamycin sulfate and ampicilli... [more]

Corresponding to the reported features of anti-VEGFR-2-approved compounds, a new 1H-indole derivative (compound 7) was designed. The inhibitory potential of the designed compound was revealed via a molecular docking study that showed the appropriate binding. Then, MD simulation (six studies) over a period of 100 ns was performed to confirm the precise binding and optimum energy. Additionally, MM-GBSA reaffirmed the perfect binding, exhibiting a total precise energy of −40.38 Kcal/Mol. The MM-GBSA experiments named the essential amino acids in the protein−ligand interaction, employing the binding energy decomposition and revealing the diversity of interactions of compound 7 inside the VEGFR-2 enzyme. As compound 7 is new, DFT experiments were utilized for molecular structure optimization. Additionally, the DFT results validated the coherent interaction of compound 7 with the VEGFR-2 enzyme. A good value of drug-likeness of compound 7 was acknowledged via in silico ADMET studies. Interes... [more]

Lichens produce a large variety of secondary metabolites with diverse bioactivities, chemical structures, and physicochemical properties. For this reason, there is a growing interest in the use of lichen-derived bioactive molecules for drug discovery and development. Here, we report on the isolation, identification, and cytotoxic evaluation of gyrophoric acid (GA) from the lichen Umbilicaria muhlenbergii, a largely unexplored and scantly described lichen species. A simple purification protocol was developed for the fractionation of lichen crude extracts with silica gel column chromatography using solvents with changing polarity. GA was identified in one of the fractions with Fourier transform infrared spectroscopy (FTIR), ion trap mass spectrometry (MS), and nuclear magnetic resonance spectroscopy (1H-NMR and 13C-NMR). The FTIR spectra demonstrated the presence of aromatic and ester functional groups C=C, C-H, and C=O bonds, with the most remarkable signals recorded at 1400 cm−1 for th... [more]

COVID-19 infection is associated with elevated oxidative stress, systemic hyper-inflammatory responses, endothelial dysfunction, and red blood cell membrane deformability. Nigella sativa extract is widely used in alternative and complementary medicine systems in a large population, due to its highly therapeutic, economic, natural, and safe nature. The aim of this study was to evaluate the effect of N. sativa extract on oxidative stress, hemolysis, proteolysis, and glycation through in vitro studies, as well as to find out its anti-viral potential against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) using in silico studies. N. sativa seed extract (at 600 µg/mL) displayed 67.33% scavenging activity in the 2,2-diphenyl-1-picrylhydrazyl (DPPH) test, and 70.28% hydrogen peroxide reducing activity. N. sativa exhibited anti-proteolytic activity by decreasing heat-induced denaturation of bovine serum albumin (BSA) and egg albumin by 63.14% and 57.95%, respectively, and exhibite... [more]

Water-based propolis extracts usually contain up to 10-fold lower quantities of active ingredients due to poor solubility in water of propolis bioactive compounds when compared with ethanol-based extracts. Since ethanol-based extracts are of limited use, water-based extracts are preferred nowadays. The application of alternative extraction techniques should be evaluated to improve extraction efficiency. Aqueous propolis extracts were prepared using purified water and propylene glycol, 2-hydroxypropyl-beta-cyclodextrin and sodium bicarbonate aqueous solutions. A microwave-assisted extraction method was applied in cycles. The total concentration of hydroxycinnamic acids in aqueous propolis extract produced by four extraction cycles was determined to be 1502.1 ± 130.1 μg/mL and 20% propylene glycol, 10% 2-hydroxypropyl-beta-cyclodextrin and 5% sodium bicarbonate aqueous solutions, increasing the total concentration of hydroxycinnamic acids by 1.6, 1.7 and 1.9-fold, respectively. An applic... [more]

The prevalence of gastric ulcers has increased in recent years, mainly because of non-steroidal anti-inflammatory drug utilization. Therefore, the current study investigates the gastroprotective effect of p-Cymene on absolute ethanol-induced acute gastric mucosal hemorrhagic lesions in rats. Thirty Sprague Dawley rats were randomly separated into five groups: normal control, ulcer control, reference, and two experimental groups. The normal and ulcer control groups were orally fed with 0.5% carboxymethylcellulose (CMC). The reference group was fed orally with 20 mg/kg omeprazole. The experimental groups were fed with 30 mg/kg and 60 mg/kg p-Cymene, respectively. After one hour, the normal group was fed with 0.5% CMC, and groups 2−5 were given absolute alcohol. After another hour all rats were sacrificed. The ulcer control group showed severe superficial hemorrhagic gastric mucosal lesions with decreased gastric mucus secretion and pH of gastric content. p-Cymene significantly reduced et... [more]

An electrochemical method for the determination of the catalytic activity of L-asparaginase (ASNase) from Erwinia carotovora was proposed. Our approach is based on the electrooxidation of amino acids from L-asparaginase polypeptide backbones. The electrochemical behavior of ASNase on electrodes obtained by screen-printing modified with single-wall carbon nanotubes (SPE/SWCNTs) as sensing elements demonstrated a broad oxidation peak at 0.5−0.6 V centered at 0.531 ± 0.010 V. We have shown that in the presence of the substrate L-asparagine, the oxidation current of the enzyme was reduced in a concentration-dependent manner. The specificity of electrochemical analysis was confirmed in experiments with glycine, an amino acid with no substrate activity on ASNase and does not reduce the oxidation peak of L-asparaginase. The addition of glycine did not significantly influence the amplitude of the oxidation current. The innovative aspects of the proposed electrochemical sensor are the direct mo... [more]

In the last decade, the green synthesis of nanoparticles has had a prominent role in scientific research for industrial and biomedical applications. In this current study, silver nitrate (AgNO3) was reduced and stabilized with an aqueous extract of Thelypteris glandulosolanosa (Raqui-raqui), forming silver nanoparticles (AgNPs-RR). UV-vis spectrophotometry, dynamic light scattering (DLS), and scanning transmission electron microscopy (STEM) were utilized to analyze the structures of AgNPs-RR. The results from this analysis showed a characteristic peak at 420 nm and a mean hydrodynamic size equal to 39.16 nm, while the STEM revealed a size distribution of 6.64−51.00 nm with an average diameter of 31.45 nm. Cellular cytotoxicity assays using MCF-7 (ATCC® HTB-22™, mammary gland breast), A549 (ATCC® CCL-185, lung epithelial carcinoma), and L929 (ATCC® CCL-1, subcutaneous connective tissue of Mus musculus) demonstrated over 42.70% of MCF-7, 59.24% of A549, and 8.80% of L929 cells had cell d... [more]

Antibacterial agents derived from classic organic compounds have been frequently employed for a number of years as a protective layer for biofilms. On the other hand, these agents often comprise dangerous components that, due to their interaction with toxic compounds, may be damaging to human beings. This hazard may be caused by the agents’ proximity to the toxic substances. Over the course of the past three decades, a variety of approaches, such as the utilization of a broad spectrum of metallic and oxide materials, have been the subject of research in order to develop a diverse selection of antibacterial coating layers that are acceptable. One of these approaches is the use of silver nanoparticles. It has been established that the cold spray technique, a solid-state method compatible with nanopowders, has shown higher performance and is the most effective strategy for coating materials. This has been proven via testing. It is possible to produce one-of-a-kind material coatings in way... [more]

(1) Background: Hedera nepalensis (Araliaceae) is a recognized medicinal plant founded in Asia that has been reported to work in antioxidant, antifungal, antimicrobial, and antitumor capacities. (2) Methods: The subcritical fluid extraction of saponin from Hedera nepalensis leaves and the optimum of the extraction process based on yield of saponin contents (by calculating the hederacoside C contents in dried Hedera nepalensis leaves) are examined by response surface methodology (RSM). Furthermore, the antimicrobial activity of the extract is tested for potential drug applications in the future. (3) Results: Based upon RSM data, the following parameters are optimal: extraction time of 3 min, extraction temperature of 150 °C, and a sample/solvent ratio of 1:55 g/mL. Under such circumstances, the achieved yield of saponin is 1.879%. Moreover, the extracts inhibit the growth of some bacterial strains (Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenza) at a moderate to... [more]

Asthma is an incurable pulmonary disease with several symptoms, including abnormal breathing, coughing, and sleep apnea, which can lead to death, and the population of asthma patients has been increasing worldwide. There are many adverse effects in current drugs, and thus, we have tried to develop anti-asthmatic agents from natural products such as Codonopsis laceolata. To define the anti-asthmatic effect and the mechanism of Codonopsis laceolata, an animal study was conducted considering different cell counts of BALF, serum IgE levels, morphological changes in the pulmonary system, the Th2 cell transcription factor (GATA-3), and the apoptotic pathway (NF-κB/COX-2). Codonopsis laceolata significantly suppressed the representative asthmatic changes, such as airway remodeling, mucous hypersecretion, epithelial hyperplasia, and inflammatory cell infiltration, in the respiratory system. It suppressed the levels of GATA-3, IL-4, and IL-13. The down-regulation of Th2-related factors, such as... [more]

An eggplant-based salad, called aubergine salad (AS), is a traditional appetizer and as such, is quite popular in the Mediterranean area. It is widely produced either on a home scale or on an industrial scale and widely consumed. However, there are cases where preservatives (such as sodium benzoate and potassium sorbate) are added in order to extend the shelf life of the product. In the present study, the stability of this delicatessen against oxidation and microbial spoilage was evaluated, with or without preservatives. The physicochemical properties of the salad were evaluated, along with the tocopherol content, resistance to oxidation, and microbial count. According to the results, it is evident that the induction period of AS is 16% (in the case that preservatives were used) and 26% (in the case without preservatives) increased, compared to a control sample (plain soybean oil). This can be attributed to the increased content in tocopherols, and more specifically to α-tocopherol. Fu... [more]

Ac-225 has lately drawn considerable attention as a radioisotope for targeted alpha therapy treatment for certain types of prostate, blood-derived, and disseminated cancers, but its supply is limited. Therefore, we investigated the production method of Ac-225 by nuclear transmutation in a fast neutron reactor. The authors investigated irradiation of Ra-226 or Th-230 as a target nuclide in the experimental fast reactor Joyo, owned and operated by Japan Atomic Energy Agency, which has abundant fast neutrons and a large loading region with high heat removal capacity. Ra-226 is in increasing demand as a target nuclide to produce Ac-225. Therefore, as another option, we selected Th-230, which is 50 times more abundant than Ra-226 in natural uranium, as an alternative nuclide. Irradiation of Ra-226 and Th-230 with high energy neutrons above the threshold causes an (n,2n) reaction, producing Ra-225 and Th-229, respectively, which are the parent nuclides of Ac-225. The analyses showed that 47... [more]

The genus Ocimum has many species that are used to treat diverse kinds of illnesses and sicknesses from ancient times. One of them, Ocimum basilicum L., commonly known as basil, has a vital role due to its various medicinal goods. It is best known as a plant with pharmacological activities, but also as an antioxidant, antimicrobial, and larvicidal agent. Although it has been traditionally used in Serbia in traditional medicine for centuries as an insecticidal, antibacterial, and antifungal plant as well as a traditional culinary plant, none of the O. basilicum varieties have been commercialised until today. There are significant numbers of information across the world that oils and by-products are part of the global market, but no references to the essential oil composition of Serbian plants were found. Therefore, the objective of this work was to evaluate the antioxidant and antimicrobial potentials of essential oil and hydrolate of two different varieties: O. basilicum var. genovese... [more]

Background: In maxillofacial surgery, critical size mandibular defects remain a challenging issue. There have been numerous attempts to improve mandibular defect healing. Recently, bone tissue engineering has provided many benefits in improving bone healing. Herein, we tried to investigate the effect of Mineralized plasmatic matrix (MPM) and Chitosan to enhance tissue healing and regeneration in mandibular bone defect. Methods: A mandibular bone defect of critical size was created in 45 New Zealand rabbits. There were three groups of rabbits: the MPM group, the Chitosan group, and the control group. Radiographical, histological, and immune histochemical evaluations were performed at 4, 8, and 12 post-operative weeks. Results: The MPM group demonstrated the highest degree of bone formation with uniform radio-opacity nearly like that of adjacent healthy parent tissue. While in the chitosan group, most of the defect area was filled with radio-opaque bone with persistent small radiolucent... [more]

The poly(o-anisidine)/BaSO4 nanocomposites were prepared by oxidative polymerization of o-anisidine monomer with BaSO4 filler for the potential antibacterial properties of the composite materials. To achieve the optimal and tunable properties of the nanocomposites, the ratio of BaSO4 filler was changed at the rates of 1%, 3%, 5%, 7%, and 10% with respect to matrix. Different analytical techniques, i.e., FTIR and UV-visible spectroscopy, were employed for functional identification and optical absorption of the poly(o-anisidine)/BaSO4 nanocomposites. The FTIR data revealed the significant interaction between POA and BaSO4, as well as the good absorption behavior of the UV-visible spectra. The conducting properties were controllable by varying the load percentage of the BaSO4 filler. Furthermore, different bacterial strains, i.e., Pseudomonas aeruginosa (Gram-negative) and Staphylococcus aureus (Gram-positive), were used to evaluate the antibacterial activity of the POA/BaSO4 nanocomposit... [more]