The purpose of this study was to evaluate the in vivo biological potential of new azetidine-2-one derivatives of ferulic acid (6a−f). First, the in vivo acute toxicity of azetidine-2-one derivatives of ferulic acid on Swiss white mice was investigated and, based on the obtained results, it can be stated that the studied derivatives belong to compounds with moderate toxicity. The in vivo anti-inflammatory potential of these derivatives was determined in a model of acute inflammation induced by carrageenan in rats and in a chronic inflammation model induced in rats using the granuloma test. In the acute inflammation model, all the studied compounds had a maximum anti-inflammatory effect 24 h after administration, which suggests that these compounds may be classified, from a pharmacokinetic point of view, in the category of long-acting compounds. The most active compound in the series was found to be compound 6b. In the case of the chronic inflammation model, it was observed that the stud... [more]

A laser ablation process assisted by the feedback of a sensor with chaotic electronic modulation is reported. A synchronous bistable logic circuit was analyzed for switching optical signals in a laser-processing technique. The output of a T-type flip-flop configuration was employed in the photodamage of NiO films. Multiphotonic effects involved in the ablation threshold were evaluated by a vectorial two-wave mixing method. A photoinduced thermal phenomenon was identified as the main physical mechanism responsible for the nonlinearity of index under nanosecond irradiation at 532 nm wavelength. Comparative experiments for destroying highly transparent human cells were carried out. Potential applications for developing hierarchical functions yielding laser-induced controlled explosions with immediate applications for biomedical photothermal processes can be contemplated.

Tissue engineering (TE) is one of the most challenging fields of research since it provides current alternative protocols and materials for the regeneration of damaged tissue. The success of TE has been mainly related to the right selection of nano-sized biocompatible materials for the development of matrixes, which can display excellent anatomical structure, functionality, mechanical properties, and histocompatibility. Today, the research community has paid particular attention to zein as a potential biomaterial for TE applications and nanotechnological approaches. Considering the properties of zein and the advances in the field, there is a need to reviewing the current state of the art of using this natural origin material for TE and nanotechnological applications. Therefore, the goal of this review paper is to elucidate the latest (over the last five years) applications and development works in the field, including TE, encapsulations of drugs, food, pesticides and bandaging for exte... [more]

Carbon dioxide is the most influential gas in greenhouse gasses and its amount in the atmosphere reached 412 µmol/mol in August 2020, which increased rapidly, by 48%, from preindustrial levels. A brand-new chemical industry, namely organic chemistry and catalysis science, must be developed with carbon dioxide (CO2) as the source of carbon. Nowadays, many techniques are available for controlling and removing carbon dioxide in different chemical processes. Since the utilization of CO2 as feedstock for a chemical commodity is of relevance today, this study will focus on how to increase CO2 solubility in culture media used for growing microbes. In this work, the CO2 solubility in a different medium was investigated. Sodium hydroxide (NaOH) and monoethanolamine (MEA) were added to the culture media (3.0 g/L dipotassium phosphate (K2HPO4), 0.2 g/L magnesium chloride (MgCl2), 0.2 g/L calcium chloride (CaCl2), and 1.0 g/L sodium chloride (NaCl)) for growing microbes in order to observe the dif... [more]

Lab-on-a-Disc (LoaD) biosensors are increasingly a promising solution for many biosensing applications. In the search for a perfect match between point-of-care (PoC) microfluidic devices and biosensors, the LoaD platform has the potential to be reliable, sensitive, low-cost, and easy-to-use. The present global pandemic draws attention to the importance of rapid sample-to-answer PoC devices for minimising manual intervention and sample manipulation, thus increasing the safety of the health professional while minimising the chances of sample contamination. A biosensor is defined by its ability to measure an analyte by converting a biological binding event to tangible analytical data. With evolving manufacturing processes for both LoaDs and biosensors, it is becoming more feasible to embed biosensors within the platform and/or to pair the microfluidic cartridges with low-cost detection systems. This review considers the basics of the centrifugal microfluidics and describes recent developm... [more]

(1) Background: shape, dimension, hemodynamics, and hemocompatibility are just a few of the several challenging key points that must be addressed in designing any suitable solution for the ventricular chamber of mechanical circulatory support devices. A preliminary evaluation of different geometries of bellow-like ventricular chambers is herein proposed. The chambers were made with a polycarbonate urethane that is acknowledged to be a hemocompatible polymer. (2) Methods: an explicit dynamic computational analysis was performed. The actuation of the three chambers was simulated without the presence of an internal fluid. Maximum stress and strain values were identified, as well as the most critical regions. Geometric changes were checked during simulated motion to verify that the dimensional constraints were satisfied. (3) Results: one chamber appeared to be the best solution compared to the others, since its dimensional variations were negligible, and effective stresses and strains did... [more]

The study aims to prepare a smart copolymeric for controlled delivery of Galantamine hydrobromide. The synthesis of the hydrogel was executed through free radical polymerization using HPMC (Hydroxypropyl methylcellulose) and pectin as polymers and acrylic acid as monomer. Cross-linking was performed by methylene bisacrylamide (MBA). HPMC-pectin-co-acrylic acid hydrogel was loaded with Galantamine hydrobromide (antidementia drug) as a model drug for treatment of Alzheimer based dementia. Formulated hydrogels (SN1−SN9) were characterized for Fourier transform-infrared spectroscopy, differential scanning calorimetry, thermogravimetric analysis, X-ray diffraction, and energy dispersive X-ray. Drug loading efficiency, gel fraction, measurements of porosity, and tensile strength were reported. Swelling and release studies were performed at pH 1.2 and 7.4. Drug liberation mechanism was evaluated by applying different release kinetic models. Galantamine hydrobromide was released from prepared... [more]

The activated sludge respiration inhibition test and the luminescent bacteria test with Vibrio fischeri are important bacterial test systems for evaluation of the toxicity of chemical compounds. These test systems were further optimized to result in better handling, reliability and sensitivity. Concerning the Vibrio fischeri test, media components such as yeast extract and bivalent cation concentrations like Ca2+ and Mg2+ were optimized. The cultivation, storage conditions and reactivation process of the stored bacteria were also improved, which enabled simpler handling and led to good reproducibility. Additionally, the respiration inhibition test with a prolonged incubation time was further analyzed using different chlorinated phenols as reference compounds. It could be stated that a longer incubation period significantly improved the sensitivity of the test system.

Improving the hygienic status of feed ingredients by biotechnological processes as fermentation is of the greatest concern. This preliminary study aimed to investigate whether there are relevant effects of fermented liquid feed (FLF) on the survival of potential pathogens in vitro. The feed (fresh basis) consisted of 50% rye, 30% rapeseed extracted meal, 10% barley and 10% wheat. Glass bottles were filled about 14.1 g water (38 °C) containing the diluted starter culture and feed (8.81 g). Fermentation led to high levels of lactate (5−7% of dry matter), low pH values (<4.0) and low levels of acetic acid (<1% of dry matter) in the FLF. The survival rate of pathogens added, such as Salmonella enterica serovar Typhimurium, Escherichia coli and Clostridium perfringens after 6 h of controlled fermentation, was significantly reduced (<2 log10 CFU/g). The counts of Candida krusei in FLF at 3 h and 6 h post inoculation remained almost unchanged regardless of the incubation time. Even a... [more]

Bone injuries that arise from trauma, cancer treatment, or infection are a major and growing global challenge. An increasingly ageing population plays a key role in this, since a growing number of fractures are due to diseases such as osteoporosis, which place a burden on healthcare systems. Current reparative strategies do not sufficiently consider cell-substrate interactions that are found in healthy tissues; therefore, the need for more complex models is clear. The creation of in vitro defined 3D microenvironments is an emerging topographically-orientated approach that provides opportunities to apply knowledge of cell migration and differentiation mechanisms to the creation of new cell substrates. Moreover, introducing biofunctional agents within in vitro models for bone regeneration has allowed, to a certain degree, the control of cell fate towards osteogenic pathways. In this research, we applied three methods for functionalizing spatially-confined electrospun artificial microenvi... [more]

In recent years, polymeric hydrogels (PolyHy) have been extensively explored for their applications in biomedicine as biosensors, in tissue engineering, diagnostic processes, and drug release. The physical and chemical properties of PolyHy indicate their potential use in regulating drug delivery. Calcineurin inhibitors, particularly cyclosporine (CsA) and tacrolimus (TAC), are two important immunosuppressor drugs prescribed upon solid organ transplants. Although these drugs have been used since the 1970s to significantly increase the survival of transplanted organs, there are concerns regarding their undesirable side effects, primarily due to their highly variable concentrations. In fact, calcineurin inhibitors lead to acute and chronic toxicities that primarily cause adverse effects such as hypertension and nephrotoxicity. It is suggested from the evidence that the encapsulation of calcineurin inhibitors into PolyHy based on polysaccharides, specifically alginate (Alg), offers effecti... [more]

High cell density cultivation (HCDC) is developed for the production of microbial biomasses and their products. They must be produced from high concentrations of substrate, e.g., glucose or sucrose. In batch culture, a high concentration of those sugars >40−50% (w/v) cannot efficiently be utilized because of a dissolved O2 limitation causing the Crabtree effect that produces toxic by-products, i.e., ethanol and/or acetate, that inhibit cell growth. To prevent this effect, the HCDC is conducted with the fed-batch strategies. However, it has many disadvantages, i.e., complicated operations. To overcome those problems, this study was designed to use a new, efficient C-source (carbon source) substrate, namely dextrin, an oligomer of glucose. It can be utilized by yeast at a very high concentration of ~100 g/L although using just batch cultivation. As it is gradually hydrolyzed to release glucose molecules and gradually assimilated into the cells as “fed-batch at the cell level” (FBC), it p... [more]

Background: Despite the widespread use of newer basal insulins, Natural Protamine Hagedorn (NPH) insulin still represents a well-established basal formulation with its long history of use, featuring the native form of human insulin. However, NPH insulin exhibits an undesirable peak within hours after a single subcutaneous (s.c.) injection, which may lead to hypoglycemia followed by insufficient basal insulin delivery. This may be attributed to the s.c. enzyme activities degrading the protamine in NPH microcrystals. Methods: A thermogelling block copolymer Pluronic® F127 (PF127) was utilized as a protective carrier for NPH microcrystals and as a modulator for insulin release from NPH. NPH insulin-loaded PF127 gel was prepared with varying concentrations of the polymer (15−25%) under mild conditions. The formulations were characterized for their gelling temperature, morphology, gel erosion, and in vitro insulin release, with trypsin concentrations up to 5 U/mL. Results: Scanning electron... [more]

Both molecular analyses and culture-dependent isolation were combined to investigate the diversity of sulfate-reducing prokaryotes and explore their role in sulfides production in full-scale anaerobic digesters (Marrakech, Morocco). At global scale, using 16S rRNA gene sequencing, Proteobacteria, Bacteroidetes, Firmicutes, Actinobacteria, Synergistetes, and Euryarchaeota were the most dominant phyla. The abundance of Archaea (3.1−5.7%) was linked with temperature. The mcrA gene ranged from 2.18 × 105 to 1.47 × 107 gene copies.g−1 of sludge. The sulfate-reducing prokaryotes, representing 5% of total sequences, involved in sulfides production were Peptococcaceae, Syntrophaceae, Desulfobulbaceae, Desulfovibrionaceae, Syntrophobacteraceae, Desulfurellaceae, and Desulfobacteraceae. Furthermore, dsrB gene ranged from 2.18 × 105 to 1.92 × 107 gene copies.g−1 of sludge. The results revealed that exploration of diversity and function of sulfate-reducing bacteria may play a key role in decreasin... [more]

The sodium triple-quantum (TQ) magnetic resonance (MR) signal created by interactions of sodium ions with macromolecules has been demonstrated to be a valuable biomarker for cell viability. The aim of this study was to monitor a cellular response using the sodium TQ signal during inhibition of Na/K-ATPase in living cancer cells (HepG2). The cells were dynamically investigated after exposure to 1 mM ouabain or K+-free medium for 60 min using an MR-compatible bioreactor system. An improved TQ time proportional phase incrementation (TQTPPI) pulse sequence with almost four times TQ signal-to-noise ratio (SNR) gain allowed for conducting experiments with 12−14 × 106 cells using a 9.4 T MR scanner. During cell intervention experiments, the sodium TQ signal increased to 138.9 ± 4.1% and 183.4 ± 8.9% for 1 mM ouabain (n = 3) and K+-free medium (n = 3), respectively. During reperfusion with normal medium, the sodium TQ signal further increased to 169.2 ± 5.3% for the ouabain experiment, while i... [more]

In this study, the effects of alginate and chitosan as entrapped materials in the biofilm formation of microbial attachment on activated carbon was determined for biohydrogen production. Five different batch fermentations, consisting of mixed concentration alginate (Alg), were carried out in a bioreactor at temperature of 60 °C and pH 6.0, using granular activated carbon (GAC) as a primer for cell attachment and colonisation. It was found that the highest hydrogen production rate (HPR) of the GAC−Alg beads was 2.47 ± 0.47 mmol H2/l.h, and the H2 yield of 2.09 ± 0.22 mol H2/mol sugar was obtained at the ratio of 2 g/L of Alg concentration. Next, the effect of chitosan (C) as an external polymer layer of the GAC−Alg beads was investigated as an alternative approach to protecting the microbial population in the biofilm in a robust environment. The formation of GAC with Alg and chitosan (GAC−AlgC) beads gave the highest HPR of 0.93 ± 0.05 mmol H2/l.h, and H2 yield of 1.11 ± 0.35 mol H2/mol... [more]

Microfluidic technology has emerged from the MEMS (Micro-Electro-Mechanical System)-technology as an important research field. During the last decade, various microfluidic technologies have been developed to open up a new era for biological studies. To understand the function of single cells, it is very important to monitor the dynamic behavior of a single cell in a living environment. Cell trapping in single cell analysis is urgently demanded There have been some review papers focusing on drug screen and cell analysis. However, cell trapping in single cell analysis has rarely been covered in the previous reviews. The present paper focuses on recent developments of cell trapping and highlights the mechanisms, governing equations and key parameters affecting the cell trapping efficiency by contact-based and contactless approach. The applications of the cell trapping method are discussed according to their basic research areas, such as biology and tissue engineering. Finally, the paper h... [more]

Recent advances in three-dimensional printing technology enable facile and on-demand fabrication of patient-specific bone scaffolds. However, there is still an urgent need for printable biomaterials with osteoinductivity. In the present study, we propose an approach to synthesize fibroblast growth factor-2 loaded-mesoporous calcium silicate nanoparticles. The growth factor loaded-nanoparticles served as fillers of polycaprolactone and then the composite scaffolds with a controlled pore structure were obtained through a fused deposition modeling technique. To evaluate the feasibility of the composite scaffolds in bone tissue engineering, drug release kinetic, bioactivity, cell proliferation, differentiation, and animal study were conducted. Our findings illustrate that utilization of mesoporous calcium silicate allowed the introduction of fibroblast growth factor-2 into the composite scaffolds through a simple soaking process and then gradually released from the scaffold to facilitate p... [more]

Glutathione transferases (GSTs) are enzymes that play a critical role in cellular detoxication by catalyzing the nucleophilic attack of glutathione on the electrophilic center of a number of xenobiotic compounds, including many therapeutic drugs. Mutations of amino acid residues in the glutathione-binding site of human glutathione transferase P1−1, namely W39C, K45A, Q52A, Q52K, and Q52E, have been engineered. The recombinant mutant proteins were expressed in Escherichia coli, but only mutants K45A, Q52A, and Q52K showed measurable activity. Steady-state kinetics comparing glutathione with the alternative thiol substrate γ-glutamylcysteine demonstrated the importance of the glycine residue in glutathione for high catalytic efficiency. Inhibition experiments with a set of glutathione analogs structurally related to the therapeutic drugs Telintra and Telcyta enabled determination of binding energies that were contributed by different substituents. The effects of substituting amino acid s... [more]

In this study, we investigate how drugs systemically affect genes via pathways by integrating information from interactions between chemical compounds and molecular expression datasets, and from pathway information such as gene sets using mathematical models. First, we adopt drug-induced gene expression datasets; then, employ gene set enrichment analysis tools for selecting candidate enrichment pathways; and lastly, implement the inverse algorithm package for identifying gene−gene regulatory networks in a pathway. We tested LY294002-induced datasets of the MCF7 breast cancer cell lines, and found a CELL CYCLE pathway with 101 genes, ERBB signaling pathway consisting of 82 genes, and MTOR pathway consisting of 45 genes. We consider two interactions: quantity strength depending on number of interactions, and quality strength depending on weight of interaction as positive (+) and negative (−) interactions. Our methods revealed ANAPC1-CDK6 (−0.412) and ORC2L- CHEK1(0.951) for the CELL CYCL... [more]

Currently available small diameter vascular conduits present several long-term limitations, which has prevented their full clinical implementation. Commercially available vascular grafts show no regenerative capabilities and eventually require surgical replacement; therefore, it is of great interest to develop alternative regenerative vascular grafts (RVG). Decellularized Small Intestinal Submucosa (SIS) is an attractive material for RVG, however, the evaluation of the performance of these grafts is challenging due to the absence of devices that mimic the conditions found in vivo. Thereby, the objective of this study is to design, manufacture and validate in silico and in vitro, a novel fluidic system for the evaluation of human umbilical vein endothelial cells (HUVECs) proliferation on SIS-based RVG under dynamical conditions. Our perfusion and rotational fluidic system was designed in Autodesk Inventor 2018. In silico Computational Fluid Dynamics (CFD) validation of the system was ca... [more]

One approach for elucidating strain-to-strain metabolic differences is the use of genome-scale metabolic models (GSMMs). To date GSMMs have not focused on the industrially important area of flavor production and, as such; do not cover all the pathways relevant to flavor formation in yeast. Moreover, current models for Saccharomyces cerevisiae generally focus on carbon-limited and/or aerobic systems, which is not pertinent to enological conditions. Here, we curate a GSMM (iWS902) to expand on the existing Ehrlich pathway and ester formation pathways central to aroma formation in industrial winemaking, in addition to the existing sulfur metabolism and medium-chain fatty acid (MCFA) pathways that also contribute to production of sensory impact molecules. After validating the model using experimental data, we predict key differences in metabolism for a strain (EC 1118) in two distinct growth conditions, including differences for aroma impact molecules such as acetic acid, tryptophol, and h... [more]

Breast cancer is the most common malignancy in both developing and developed countries. In this study, we simultaneously analyzed nine constituent compounds from Spatholobi Caulis (gallic acid, (−)-gallocatechin, 3,4-dihydroxybenzoic acid, procyanidin B1, 3,4-dihydroxybenzaldehyde, catechin, procyanidin B2, epicatechin, and (−)-epicatechin gallate) and examined their anticancer effects on MCF-7 and MDA-MB-231 human breast cancer cells. The experimental results indicated that the gallic acid showed the strongest cytotoxic effect on MCF-7 cells among tested compounds whilst most of samples did not express inhibitory effect on viability of MDA-MB-231 cells, except for 70% ethanol extract of S. Caulis. Thus, gallic acid was chosen to extend anticancer mechanism study on MCF-7 cells. Our data showed that the gallic acid induced apoptotic MCF-7 cell death through both extrinsic and intrinsic pathways, which increased the expression of cleaved caspase-7, -8, and -9, Bax and p53, but reduced t... [more]

Non-alcoholic fatty liver disease (NAFLD) is a disease associated with metabolic syndromes such as diabetes and obesity, regardless of alcohol consumption, and refers to the accumulation of triacylglycerols in the liver. Thymol (THY) is a vegetable essential oil that is naturally contained in the Zingiberaceae and Lamiaceae families. THY was isolated from Curcuma longa L. The rhizomes of Curcuma longa L. were dried, sliced and extracted with 50% ethanol and then isolated through repeated column chromatography. This study was conducted to investigate the inhibitory effect of THY, even in non-alcoholic fatty liver disease, in relation to the inhibiting hyperlipidemia effect of THY, which was demonstrated in previous studies. Hepatocytes were treated with oleate (OA) containing THY to observe lipid accumulation by Oil Red O staining (ORO). We also tested the effect of THY on triacylglycerols (TG) and total cholesterol (TC) in HepG2 cells. Western blot and real-time RT-PCR using sterol reg... [more]

In recent years, nanotechnology has attracted attention in many fields because it has several up-and-coming novel uses. Many researchers have suggested that chitosan nanoparticles (CS-NPs) and their derivatives are one of the best nanomaterials for delivering antibacterial activity. CS-NPs have a broad spectrum of antibacterial activity, but they manifest different inhibitory efficacy against gram-negative (G−) and gram-positive (G+) bacterial species. The mechanism of antibacterial action is an intricate process that varies between G− and G+ bacteria as a result of the differences in cell wall and cell membrane chemistry. In previous studies, greater antibacterial activity was more evident against G− bacteria than G+ bacteria, whereas in some studies G+ bacteria were more sensitive. Researchers predicted that the varied responses of bacteria are caused by the mixed hydrophilicity and negative charge distribution on the bacterial surface. Moreover, its activity depends on a number of v... [more]