The increasing clinical use of artificial medical devices raises the issue of microbial contamination, which is a risk factor for the occurrence of biofilm-associated infections. A huge amount of scientific data highlights the promising potential of essential oils (EOs) to be used for the development of novel antibiofilm strategies. We aimed to review the relevant literature indexed in PubMed and Embase and to identify the recent directions in the field of EOs, as a new modality to eradicate microbial biofilms. We paid special attention to studies that explain the mechanisms of the microbicidal and antibiofilm activity of EOs, as well as their synergism with other antimicrobials. The EOs are difficult to test for their antimicrobial activity due to lipophilicity and volatility, so we have presented recent methods that facilitate these tests. There are presented the applications of EOs in chronic wounds and biofilm-mediated infection treatment, in the food industry and as air disinfecta... [more]

Pesticide by-products found in soil are usually more toxic and persistent than the pesticides themselves. For example, Endosulfan lactone (EL) (a by-product of the organochloride pesticide endosulfan). EL is created by the enzymatic activity (and related oxidative processes) of microorganisms in the soil. A sustainable method of EL removal is the introduction of Eisenia fetida earthworm. In this paper, it will be demonstrated the impact of vermicomposting process related to Eisenia fetida earthworm on EL by measuring initial and final concentrations of the compound and overall enzymatic activity in sterile and non-sterile solid substrate over 56 days. As a baseline, it be observed there were higher EL removals in non-sterile solid substrate (90.86%) at day 5 than in sterile solid substrate (83.86%) at day 14. In samples with Eisenia fetida, the presence of EL in non-sterile solid substrate was 36%, however in sterile solid substrate it was only 18% at day 1 and 7, with a maximum enzyme... [more]

Plasma protein binding plays a critical role in drug therapy, being a key part in the characterization of any compound. Among other methods, this process is largely studied by ultrafiltration based on its advantages. However, the method also has some limitations that could negatively influence the experimental results. The aim of this study was to underline key aspects regarding the limitations of the ultrafiltration method, and the potential ways to overcome them. The main limitations are given by the non-specific binding of the substances, the effect of the volume ratio obtained, and the need of a rigorous control of the experimental conditions, especially pH and temperature. This review presents a variety of methods that can hypothetically reduce the limitations, and concludes that ultrafiltration remains a reliable method for the study of protein binding. However, the methodology of the study should be carefully chosen.

Despite the significant progress in anticancer drug development over recent years, there is a vital need for newer agents with unique, but still effective, mechanisms of action in order to treat the disease, particularly the highly aggressive and drug-resistant types. Alkylating agents, in particular nitrogen-based alkylators, are commonly used to treat hematological and solid malignancies; they exert their antineoplastic effects at all phases of the cell cycle and prevent reproduction of tumor cells. Certain alkylating agents have been designed to be more lipophilic, enabling the compound to penetrate the cell and enhance its alkylating activity against tumors. This review details the evolution of currently available alkylating agents and their profiles, with a focus on nitrogen-based alkylating agents, as important anticancer therapy strategies.

Lipophilicity is one of the most important parameters determining the pharmacodynamic and pharmacokinetic properties, as well as the toxicity of many compounds. The subject of the research was to determine the lipophilicity of betulin-1,4-quinone hybrids using thin layer chromatography in reverse phase system and computer programs to calculate its theoretical models. The correlation between the experimental and theoretical values of lipophilicity was analyzed. Lipinski’s and Veber’s rules, as well as penetration through the blood−brain barrier were also determined using computer programs. For all of the analyzed values, a similarity analysis was performed. The dendrograms for the experimental and theoretical lipophilicity show that there is a correlation between them. However, the dendrograms for the experimental lipophilicity and pharmacokinetic parameters indicate that there is no correlation between the structure and the pharmacological properties. Hybrids exhibit a high biological... [more]

The enormous library of pharmaceutical compounds presents endless research avenues. However, several factors limit the therapeutic potential of these drugs, such as drug resistance, stability, off-target toxicity, and inadequate delivery to the site of action. Extracellular vesicles (EVs) are lipid bilayer-delimited particles and are naturally released from cells. Growing evidence shows that EVs have great potential to serve as effective drug carriers. Since EVs can not only transfer biological information, but also effectively deliver hydrophobic drugs into cells, the application of EVs as a novel drug delivery system has attracted considerable scientific interest. Recently, EVs loaded with siRNA, miRNA, mRNA, CRISPR/Cas9, proteins, or therapeutic drugs show improved delivery efficiency and drug effect. In this review, we summarize the methods used for the cargo loading into EVs, including siRNA, miRNA, mRNA, CRISPR/Cas9, proteins, and therapeutic drugs. Furthermore, we also include t... [more]

Plasmin (Plm), a trypsin-like serine protease, is responsible for fibrinolysis pathway and pathologic events, such as angiogenesis, tumor invasion, and metastasis, and alters the expression of cytokines. A growing body of data indicates that a Plm inhibitor is a potential candidate as an anti-inflammatory and anti-cancer agent. A class of active site-directed plasmin inhibitors containing tranexamic acid residue has been designed. As evidenced by docking studies, the inhibitor binds to the active site not to the lysine binding site (LBS) in plasmin, thus preventing plasmin from digesting the substrate. Further optimization of the series, concerning both activity and selectivity, led to the second generation of inhibitors. This review focuses on the Plm inhibitory activity-structure relationship of Plm inhibitors with the goal of realizing their design and clinical application.

In this work was evaluated the effect of sequential inoculum of Hanseniaspora uvarum AS27 strain and a commercial Saccharomyces cerevisiae yeast on the physical−chemical and organoleptic features of Aglianico, a traditional red wine of Southern Italy. Four fermentation treatments on a pilot scale were performed. In fermentation treatment A, the alcoholic fermentation was spontaneously conducted by the indigenous yeasts present in grape must. In the fermentation treatments B and C were inoculated respectively S. cerevisiae FE and H. uvarum AS27 strains, as a single starter. The fermentation treatment D was initially inoculated with H. uvarum AS27, and S. cerevisiae strain was added after 72 h (sequential inoculation). Microbiological, physical−chemical parameters and sensory profiles of the wines have been defined. The results showed that the use of H. uvarum AS27, in sequential inoculum with S. cerevisiae FE, influenced the wine composition, enriching it in polyphenolic and volatile co... [more]

Studying cell metabolism serves a plethora of objectives such as the enhancement of bioprocess performance, and advancement in the understanding of cell biology, of drug target discovery, and in metabolic therapy. Remarkable successes in these fields emerged from heuristics approaches, for instance, with the introduction of effective strategies for genetic modifications, drug developments and optimization of bioprocess management. However, heuristics approaches have showed significant shortcomings, such as to describe regulation of metabolic pathways and to extrapolate experimental conditions. In the specific case of bioprocess management, such shortcomings limit their capacity to increase product quality, while maintaining desirable productivity and reproducibility levels. For instance, since heuristics approaches are not capable of prediction of the cellular functions under varying experimental conditions, they may lead to sub-optimal processes. Also, such approaches used for bioproc... [more]

Most cells within the human body interact with neighboring cells and extracellular matrix (ECM) components to establish a unique 3D organization. These cell−cell and cell−ECM interactions form a complex communication network of biochemical and mechanical signals critical for normal cell physiology. The behavior of cells in a 3D environment is fundamentally different from that of cells in monolayer culture. Aggregation can affect cell−cell interactions, being more representative of the normal tissue microenvironment. Therefore, 3D cell culture technologies have been developed. The general method for cell aggregate is a physical method; it is difficult to control the size and number of cell aggregates. In any case, no chemical method has been discovered yet, so a new method to solve these problems is needed. In this paper, we describe the induction of a cell aggregate of the newly discovered (Lys-Pro)12(KP24) peptide. Since it was revealed that KP24 had cell aggregate-inducing activity,... [more]

The aim of the study was to determine oxidation potential of selected persistent, environmentally relevant antibiotics (Amoxicillin, Levofloxacin, and their mixture with Vancomycin) to reduce their environmental emissions. Ozonation (O3) and indirect ozonation at pH 9.5 (O3/pH9.5) were catalytically enhanced by addition of Fe2+ (O3/Fe2+) and photocatalytic ozonation in combination with Fe2+ and UV-A black light (O3/Fe2+/UV) at two temperatures using total organic carbon (TOC) and chemical oxygen demand (COD) to identify formation of by-products. Oxidative degradation followed pseudo-first order consecutive reactions. Initial phase of oxidation was more intensive than mineralisation at 21 and 40 °C: up to 57.3% and 69.2%, respectively. After 120 min mineralization at 21 °C was up to 64.9% while at 40 °C it was up to 84.6%. Oxidation reached up to 86.6% and 93.4% at 21 °C and 40 °C, respectively. The most efficient processes were indirect ozonation at pH 9.5 (O3/pH9.5) (up to 93.4%) and... [more]

Tripartite motif 21 (TRIM21) plays an important role in hepatocellular carcinoma (HCC). However, the gene polymorphisms of TRIM21 in HCC is not as well known. In this study, two single nucleotide polymorphisms (SNPs) in the TRIM21 gene, rs4144331, and re915956, were selected to investigate correlations between these SNPs and susceptibility to HCC. Two SNPs of the TRIM21 gene from 1196 controls without cancer and 394 HCC patients were analyzed using real-time polymerase chain reaction. These results were further analyzed to expound the associations between these TRIM21 polymorphisms and the risk of HCC as well as the impact of these SNPs on clinicopathological characteristics of HCC. After adjustment for other covariants, we observed that that younger patients (<65 years) with the TRIM21 rs915956 A allele had a probability of HCC (AOR = 3.153, 95% CI: 1.315−7.516, p = 0.010). Moreover, patients with a smoking habit who carried the T allele of rs4144331 had more probability of HCC (AO... [more]

Supercritical carbon dioxide + ethanol (SC-CO2+EtOH) extraction, was employed as a deflavoring method to improve the sensory properties of pea flours. Furthermore, the impacts of particle size along with extraction on volatile profile and sensory attributes of pea flours were investigated using multiple approaches. These included headspace solid-phase microextraction-gas chromatography (HS-SPME-GC), GC-olfactometry (GC-O), and quantitative descriptive analysis (QDA) using a trained sensory panel. Total volatile contents of non-deflavored and deflavored whole pea flour and its fractions were in the range of 7.1 ± 0.3 to 18.1 ± 1.0 µg/g and 0.4 ± 0.1 to 2.7 ± 0.4 µg/g, respectively. The GC-O system showed that the total volatile intensity was in the range of 14.5 to 22.0 and 0 to 3.5, for non-deflavored and deflavored pea flours, respectively. Volatile analyses indicated that 1-hexanol, 1-octanol, 1-nonanol, nonanal, and 2-alkyl methoxypyrazines were major off-aroma compounds. Most off-a... [more]

The integration of real time release testing into an advanced process control (APC) concept in combination with digital twins accelerates the process towards autonomous operation. In order to implement this, on the one hand, measurement technology is required that is capable of measuring relevant process data online, and on the other hand, a suitable model must be available to calculate new process parameters from this data, which are then used for process control. Therefore, the feasibility of online measurement techniques including Raman-spectroscopy, attenuated total reflection Fourier transformed infrared spectroscopy (ATR-FTIR), diode array detector (DAD) and fluorescence is demonstrated within the framework of the process analytical technology (PAT) initiative. The best result is achieved by Raman, which reliably detected mAb concentration (R2 of 0.93) and purity (R2 of 0.85) in real time, followed by DAD. Furthermore, the combination of DAD and Raman has been investigated, which... [more]

Although many benefits drawn from beer consumption are claimed, the epidemiological records are contradictory with respect to cancer prevention. The purpose of this study was to investigate the possible health-related activities involving genome safety and the ageing processes of two types of lyophilised ale beers (blond and stout), as well as two of their bioactive compounds (tyrosol and iso-alpha humulone). A multipurpose trial set of in vivo toxicity, antitoxicity, mutagenicity, antimutagenicity, lifespan and healthspan assays using Drosophila melanogaster were used. In parallel, several in vitro assays were designed using the cancer cell line HL-60 in order to establish the possible chemopreventive activity of the selected substances, where epigenetic modulation of DNA methylation changes, clastogenic activity and tumour cell inhibition growth were evaluated. The safety of the four substances was confirmed: lyophilised blond ale beer (LBAB), lyophilised stout ale beer (LSAB), tyros... [more]

Cubing machines in food processing have evolved over the years, which have made products like Star®, Knorr®, and Chicken® bouillon cubes become commercially available today, even in many parts of Africa. On the other hand, the fermented mesquite seed “okpeye” food condiment, traditionally produced by well-trained artisans and widely utilised in Nigeria, requires further product development in order to compete with bouillon cubes. Quality comparisons between the cubed “okpeye” condiment and commercially available bouillon cube products have not yet been reported. Therefore, cubing fabrication/costing and machine performance on African fermented “okpeye” condiment quality attributes, compared with commercial bouillon types, were done. The processing of mesquite seeds into the “okpeye” condiment resembled those of artisans. Bouillon cube products involved the Star®, Knorr®, and Chicken® types. Quality attributes involved proximate, micronutrient, phytochemical, and microbial aspects. Resu... [more]

This study proposes a reliable inline PAT concept for the simultaneous monitoring of different product components after chromatography. The feed for purification consisted of four main components, IgG monomer, dimer, and two lower molecular weight components of 4.4 kDa and 1 kDa molecular weight. The proposed measurement setup consists of a UV−VIS diode-array detector and a fluorescence detector. Applying this system, a R2 of 0.93 for the target component, a R2 of 0.67 for the dimer, a R2 of 0.91 for the first side component and a R2 of 0.93 for the second side component is achieved. Root mean square error for IgG monomer was 0.027 g/L, for dimer 0.0047 g/L, for side component 1 0.016 g/L and for the side component 2 0.014 g/L. The proposed measurement concept tracked component concentration reliably down to 0.05 g/L. Zero-point fluctuations were kept within a standard deviation of 0.018 g/L for samples with no IgG concentration but with side components present, allowing a reliable det... [more]

The valorization of Spirulina as a potential biosorption material to treat contaminated wastewater was evaluated. Batch experiments were conducted to study the influence of pH value and ionic strength on the biosorption capacity of Spirulina. Higher removal capacity was observed at pH 5.2, while higher ionic strength was found to result in lower adsorption capacity, which suggests that ion exchange is a relevant mechanism for Pb (II) adsorption on Spirulina. The immobilization of Spirulina on alginate beads was found not only to increase the adsorption capacity, but also to overcome limitations such as unacceptable pressure drops on column systems. The Langmuir model was the most appropriate model to describe the biosorption equilibrium of lead by free and immobilized Spirulina. The experimental breakthrough curves were evaluated using the Thomas, Bohart-Adams, and dose-response models. The experimental results were most properly described by the dose-response model, which is consisten... [more]

Breast cancer is the most common neoplasm and the leading cause of cancer death in women worldwide. Although 5-fluorouracil is a conventional chemotherapeutic agent for breast cancer treatment, its use may result in severe side effects. Thus, there is widespread interest in lowering 5-fluorouracil drawbacks, without affecting its therapeutic efficacy by the concomitant use with natural products. Herein, we aimed at evaluating whether α-mangostin, a natural antineoplastic compound, could increase the anticancer effect of 5-fluorouracil in different breast cancer cell lines, allowing for dose reduction. Cell proliferation was evaluated by sulforhodamine-B assays, inhibitory concentrations and potency were calculated by dose-response curves, followed by analysis of their pharmacological interaction by the combination-index method and dose-reduction index. Cell cycle distribution was evaluated by flow cytometry. Each compound inhibited cell proliferation in a dose-dependent manner, the tri... [more]

Conjugated linoleic acids (CLA) are distinctive polyunsaturated fatty acids. They are present in food produced by ruminant animals and they are accumulated in seeds of certain plants. These naturally occurring substances have demonstrated to have anti-carcinogenic activity. Their potential effect to inhibit cancer has been shown in vivo and in vitro studies. In this review, we present the multiple effects of CLA isomers on cancer development such as anti-tumor efficiency, anti-mutagenic and anti-oxidant activity. Although the majority of the studies in vivo and in vitro summarized in this review have demonstrated beneficial effects of CLA on the proliferation and apoptosis of tumor cells, further experimental work is needed to estimate the true value of CLA as a real anti-cancer agent.

Ondansetron (OND) is a serotonin type 3 receptor antagonist that exhibits antiemetic activity. From the clinical point of view, vomiting and nausea prevention is an important task. Anticancer treatment and recovery impact the patient’s overall state by affecting appetite, well-being, and physical activity, and consequently, nutrition quality. Depending on the patient’s indication and condition, parenteral nutrition is administered to meet full nutritional requirements. In addition, antiemetic drugs can be added to the parenteral nutrition (PN) admixture to treat chemo- or radio-therapy-induced nausea and vomiting. However, adding any medication to the PN admixture can result in the instability of the composition in the overall admixture. This study aimed to develop the HPLC method of determination of OND in Lipoflex special, one of the most popular, ready-to-use PN admixtures. The proposed HPLC method and the sample preparation procedure were suitable for analyzing OND in PN admixture... [more]

Production of small-sized peptides is significant because of their health benefits. Ultrafiltration (UF) membrane provides an effective fractionation of small-sized peptides on a large scale. Thus, the present study was aimed to evaluate the performance of multilayer UF membrane in fractionating tilapia fish by-product (TB) protein hydrolysate by observing the permeate flux, peptide transmission, and peptide distribution under different stirring speed, pH of feed solution, and salt concentration (NaCl). The fractionation process was carried out using a dead-end UF membrane system that consists of a stack of two membrane sheets with different (10/5 kDa) and similar (5/5 kDa) pore sizes in one device. The highest permeate flux (10/5 kDa−39.5 to 47.3 L/m2.h; 5/5 kDa− 15.8 to 20.3 L/m2.h) and peptide transmission (10/5 kDa−51.8 to 61.0%; 5/5 kDa−18.3 to 23.3%) for both multilayer membrane configurations were obtained at 3.0 bar, 600 rpm, pH 8, and without the addition of salt. It was also... [more]

The eggplant is an important vegetable that is used all over the world and it contains valuable bioactive properties. Cooking methods affect the nutritional value as well as the functional characteristics of vegetables. This study investigated the effect of air-frying at different temperatures and the extraction solvents on the bioactive properties of eggplant. The eggplant air-fried for 25 min and extracted with 50% ethanol exhibited the highest total flavonoid content (35.10 mg catechin equivalent per gram dry weight), while its total polyphenol content was found as 87.81 mg gallic acid equivalent per gram dry weight. The uncooked sample exhibited the lowest DPPH scavenging (IC50: 422.12 mg/mL reducing power: 0.914), while the highest DPPH scavenging activity (IC50: 2.87 mg/mL; reducing power: 0.936) was recorded for the sample air-fried for 25 min and extracted with 50% ethanol. The highest amount of tannic acid was found in medium-cooked eggplant, while chlorogenic acid was the hig... [more]

High fructose diet causes metabolic syndrome and induces host gut microbial dysbiosis and related obesity and nonalcoholic fatty liver disease (NAFLD). Several antibiotic treatments could prevent fatty liver. However, there are studies that have demonstrated that a high-fructose diet could influence the gut microbial dysbiosis and induce fatty liver. The purpose of this study was performed to partially modify the gut bacterial composition with a single cefotaxime treatment, which might affect the fructose-induced NAFLD severity. The C57BL/6JNarl male mice were divided into four groups including vehicle/chow diet (VE-CD), vehicle/high-fructose diet (VE-FD), antibiotic (cefotaxime (CF))/CD, and CF/FD. The results showed that body weight gain, moderate hepatic steatosis severity, epididymal white adipose tissue hypertrophy, and insulin resistance occurrence with NAFLD-related symptoms were observed only in the CF-FD group. The raised protein expression of hepatic lipogenesis was observed... [more]

In this study, a low-cost chemically defined (CD) culture medium was proposed and evaluated with the aim of replacing culture media such as yeast mold (YM) and yeast peptone dextrose (YPD), commonly used for growth and carotenoid production by Xanthophyllomyces dendrorhous. Initially, the CD culture medium was compared to the YM and YPD. The growth in optical density (OD) and carotenoid production (mg/L) of the cultures reached 4.88, 6.76, 5.79, and 0.67, 0.92, and 0.69, respectively. The CD culture served as the basis of an improved specific culture medium containing industrial glucose. Additionally, in this new formulation, vitamins, glutamate, and other compounds were evaluated. Industrial glucose more than doubled carotenoid production; however, the addition of vitamins was not essential for X. dendrorhous cultivation. Moreover, glutamate and Na2HPO4 proved to be highly significant factors (p-value < 0.05), increasing carotenoid biosynthesis from 0.67 to 1.33 mg/L. The specific... [more]