Oxidative stress is a prominent event in several acute and chronic diseases including neoplasia. Although its direct involvement in carcinogenesis still remains to be clearly defined, a deeper knowledge of oxidative stress in oncologic patients could help to monitor their clinical outcome and to develop new therapeutic approaches. Therefore, the present study was undertaken to explore redox status in blood of neoplastic dogs affected either by multicentric lymphoma or by primary cutaneous mastocytoma. Superoxide anion (O2 •−), nitric oxide (NO) and hydroperoxides (ROOH) were measured. Detoxifying enzyme superoxide dismutase (SOD) and total non-enzymatic antioxidant capacity (ferric reducing-antioxidant power (FRAP)) were assessed. The oxidative stress index (OSi) both for enzymatic (OSiE) and non-enzymatic (OSiNE) scavengers were evaluated. Both pathologies, showed a reduced NO generation, while O2 •− levels were decreased only in mastocytoma. The oxidative stress indexes showed a sign... [more]

The paper describes the process of n-butanol abatement by unicellular fungi, able to deplete n-butanol content in gas, by using n-butanol as source of carbon. Isolated and identified fungi species Candida albicans and Candida subhashii were subjected to a viability process via assimilation of carbon from hydrophilic and hydrophobic compounds. The isolates, which exhibited the ability to assimilate carbon, were immobilized on four different types of artificial support materials used for biotrickling filtration. Application of optical microscopy, flow cytometry and the tests employing propidium iodide and annexin V revealed viability of the fungi isolated on support materials’ surfaces at the average level of 95%. The proposed method of immobilization and its evaluation appeared to be effective, cheap and fast. Based on performed comparative analyses, it was shown that polyurethane foam and Bialecki rings (25 × 25) could be attractive support materials in biotrickling filtration.

Moringa extract was microencapsulated for the first time by spray-drying technique using tragacanth gum (MorTG) to improve its stability under gastrointestinal and storage conditions, assessing total polyphenolic content (TPC) and antioxidant activity. Additionally, cytotoxicity of the microencapsulated components was evaluated after contact with Caco-2 cells. Results showed that TPC was released as follows—oral (9.7%) < gastric (35.2%) < intestinal (57.6%). In addition, the antioxidant activity in in vitro digestion reached up to 16.76 ±0.15 mg GAE g−1, which was 300% higher than the initial value. Furthermore, microencapsulated moringa extract presented a half-life up to 45 days of storage, where the noticeably change was observed at 35 °C and 52.9% relative humidity. Finally, direct treatment with 0.125 mg mL−1 MorTG on Caco-2 cells showed a slight antiproliferative effect, with a cell viability of approx. 87%. Caco-2 cells’ viability demonstrated non-cytotoxicity, supporting... [more]

Despite all the progresses made by metabolic engineering, still only a few biotechnological processes are running at an industrial level. In order to boost the biotechnological sector, integration strategies as well as long-term views are needed. The aim of the present review is to identify the main drawbacks in biotechnological processes, and to propose possible solutions to overcome the issues in question. Novel cell factories and bioreactor design are discussed as possible solutions. In particular, the following microorganisms: Yarrowia lipolytica, Trichosporon oleaginosus, Ustilago cynodontis, Debaryomyces hansenii along with sequential bioreactor configurations are presented as possible cell factories and bioreactor design solutions, respectively.

Janus kinase 3 (JAK3) inhibitors have been used effectively in the treatment of several cases of alopecia universalis and its variants. Our study aims to evaluate whether the emulsion extract of brevilin A from Centipeda minima (CMX) stimulates hair regrowth in a clinical trial, as a JAK3 inhibitor, combined with network pharmacology-based analysis. CMX showed potent inhibition of JAK3 in a concentration-dependent manner. Significant differences in total hair count, terminal hair count, and anagen hair count from the baseline to 24 weeks were observed between the placebo and CMX subjects. The gene set enrichment analysis showed that the targets of CMX are mainly associated with the JAK-STAT signaling pathway, cytokine−cytokine receptor interactions, and the MAPK signaling pathway. This study suggests that the medicinal herbal extract CMX is useful in the treatment of mild to moderate vertex balding that contribute to the visible improvements in hair growth observed in treated patients.

This work highlights the role of process system engineering (PSE) principles (especially simulation and optimization) in the development of a COVID-19 vaccine and other kinds of vaccines. As a result of a unique multi-national collaboration of PSE-minded chemical engineers, immunologists, and pathologists, we have created computer models of how the human body's immune system responds to vaccine injections of various kinds. The STochastic Omentum REsponse model (STORE) is stochastic, agent-based, and dynamic, and tracks how T-cells and antigen presenting cells interact, change, divide, and respond after an immune event such as a vaccine injection or an infection. Using model parameters related to dosage, injection schedule, genetic traits of the patient, and various vaccine or immune system properties, the STORE model can be used to predict how the human body responds in the days and weeks after a vaccine injection.

The STORE model consists of a collection of small, agent-based mode... [more]

The global burden of cancer is on the rise, and as a result, the number of therapeutics administered for chemotherapy is increasing. The occupational exposure, recalcitrant nature and ecotoxicological toxicity of these therapeutics, referred to as antineoplastic (ANP) drugs, have raised concerns about their safe remediation. This review provides an overview of the environmental source of ANPs agents, with emphasis on the currently used remediation approaches. Outpatient excreta, hospital effluents, and waste from pharmaceutical industries are the primary source of ANP waste. The current review describes various biotic and abiotic methods used in the remediation of ANP drugs in the environment. Abiotic methods often generate transformation products (TPs) of unknown toxicity. In this light, obtaining data on the environmental toxicity of ANPs and its TPs is crucial to determine their toxic effect on the ecosystem. We also discuss the biodegradation of ANP drugs using monoculture of funga... [more]

Phenol degradation by Pseudomonas putida BCRC 14365 was investigated at 30 °C and a pH of 5.0−9.0 in the batch tests. Experimental results for both free and immobilized cells demonstrated that a maximum phenol degradation rate occurred at an initial pH of 7. The peak value of phenol degradation rates by the free and immobilized cells were 2.84 and 2.64 mg/L-h, respectively. Considering the culture at 20 °C, there was a lag period of approximately 44 h prior to the start of the phenol degradation for both free and immobilized cells. At the temperatures ranging from 25 to 40 °C, the immobilized cells had a higher rate of phenol degradation compared to the free cells. Moreover, the removal efficiencies of phenol degradation at the final stage were 59.3−92% and 87.5−92%, for the free and immobilized cells, respectively. The optimal temperature was 30 °C for free and immobilized cells. In the batch experiments with various initial phenol concentrations of 68.3−563.4 mg/L, the lag phase was... [more]

RNA viruses, such as influenza and Severe Acute Respiratory Syndrome (SARS), invoke excessive immune responses; however, the kinetics that regulate inflammatory responses within infected cells remain unresolved. Here, we develop a mathematical model of the RNA virus sensing pathways, to determine the intracellular events that primarily regulate interferon, an important protein for the activation and management of inflammation. Within the ordinary differential equation (ODE) model, we incorporate viral replication, cell death, interferon stimulated genes’ antagonistic effects on viral replication, and virus sensor protein (TLR and RIG-I) kinetics. The model is parameterized to influenza infection data using Markov chain Monte Carlo and then validated against infection data from an NS1 knockout strain of influenza, demonstrating that RIG-I antagonism significantly alters cytokine signaling trajectory. Global sensitivity analysis suggests that paracrine signaling is responsible for the ma... [more]

Unfavorable prognoses and low survival rates are specific features of metastatic melanoma that justify the concern for the development of new therapeutic strategies. Lately, nanotechnology has become an attractive field of study due to recent advances in nanomedicine. Using a chick chorioallantoic membrane (CAM) implanted with xenografts harvested from C57BL/6 mice with B16F10 melanoma cells, we studied the effects of iron oxide nanoparticles functionalized with salicylic acid (SaMNPs) as a form of therapy on the local development of xenotransplants and CAM vessels. The SaMNPs induced an anti-angiogenic effect on the CAM vessels, which accumulated preferentially in the melanoma cells and induced apoptosis and extensive xenograft necrosis. As a result, this slowed the increase in the xenograft volume and reduced the melanoma cells’ ability to metastasize locally and distally. Further, we demonstrate the use of the chick CAM model as a tool for testing the action of newly synthesized nan... [more]

The study aimed to assess the aldose reductase (AR) inhibition of selected Geranium species and determine the bioactive flavonoid constituents. Flavonoids are known to be good AR inhibitors. Among the species examined, G. sibiricum exhibited potent inhibition of AR (IC50 value, 2.4 µg/mL). Further examination of G. sibiricum, after solvent extraction and fractionation, revealed that the ethyl acetate fraction (IC50 value, 0.41 µg/mL) had a potent AR inhibitory effect. Kaempferol rhamnosides were the active compounds from this fraction. Moreover, G. sibiricum showed the highest content of kaempferol-7-O-rhamnoside and kaempferol-3,7-O-dirhamnoside among the samples examined with a concentration in the extracts of 28.1 and 2.2 mg/g, respectively. This study shows that G. sibiricum exhibits promising AR inhibitory activity, which can be explored further as a natural therapy for treating and managing complications associated with diabetes.

Milling is an essential unit operation used for particle size reduction in solid oral dosage manufacturing. The breakage of particles in a comil is due to the intense shear applied on the particles between impeller and the screen. Breakage also occurs due to the impact from a rotating impeller. Particles exit the mill based on their size relative to the aperture size of the screen bores. This study was set up to understand the working of the comil better. A new CPP (Critical Process Parameter), in the form of batch loading was identified. It was found that there are two different regimes (quasi static regime and impact regime) in which a comil generally operates, and the effect of the CPP’s (batch loading and impeller speed) on these regimes was studied. Knowledge of the effect of upstream operations on a particular unit operation is of significant importance, especially for pharmaceutical industry. For this reason, the effect of granulation variables such as liquid-to-solid ratio, gra... [more]

Oxaliplatin is a chemotherapeutic drug widely used to treat various types of tumors. However, it can induce a serious peripheral neuropathy characterized by cold and mechanical allodynia that can even disrupt the treatment schedule. Since the approval of the agent, many laboratories, including ours, have focused their research on finding a drug or method to decrease this side effect. However, to date no drug that can effectively reduce the pain without causing any adverse events has been developed, and the mechanism of the action of oxaliplatin is not clearly understood. On the dorsal root ganglia (DRG) sensory neurons, oxaliplatin is reported to modify their functions, such as the propagation of the action potential and induction of neuropathic pain. Voltage-gated sodium channels in the DRG neurons are important, as they play a major role in the excitability of the cell by initiating the action potential. Thus, in this small review, eight studies that investigated the effect of oxalip... [more]

Cell-free systems are a widely used research tool in systems and synthetic biology and a promising platform for manufacturing of proteins and chemicals. In the past, cell-free biology was primarily used to better understand fundamental biochemical processes. Notably, E. coli cell-free extracts were used in the 1960s to decipher the sequencing of the genetic code. Since then, the transcription and translation capabilities of cell-free systems have been repeatedly optimized to improve energy efficiency and product yield. Today, cell-free systems, in combination with the rise of synthetic biology, have taken on a new role as a promising technology for just-in-time manufacturing of therapeutically important biologics and high-value small molecules. They have also been implemented at an industrial scale for the production of antibodies and cytokines. In this review, we discuss the evolution of cell-free technologies, in particular advancements in extract preparation, cell-free protein synth... [more]

Cupriavidus necator DSM 545 can utilise glycerol to synthesise poly(3-hydroxybutyric acid) under unbalanced growth conditions, i.e., nitrogen limitation. To improve poly(3-hydroxybutyric acid) (PHB) batch production by C. necator through model-guided bioprocessing or genetic engineering, insights into the dynamic effect of the fermentation conditions on cell metabolism are crucial. In this work, we have used dynamic flux balance analysis (DFBA), a constrained-based stoichiometric modelling approach, to study the metabolic change associated with PHB synthesis during batch cultivation. The model employs the ‘minimisation of all fluxes’ as cellular objectives and measured extracellular fluxes as additional constraints. The mass balance constraints are further adjusted based on thermodynamic considerations. The resultant flux distribution profiles characterise the evolution of metabolic states due to adaptation to dynamic extracellular conditions and provide further insights towards improv... [more]

Following the success of and the high demand for recombinant protein-based therapeutics during the last 25 years, the pharmaceutical industry has invested significantly in the development of novel treatments based on biologics. Mammalian cells are the major production systems for these complex biopharmaceuticals, with Chinese hamster ovary (CHO) cell lines as the most important players. Over the years, various engineering strategies and modeling approaches have been used to improve microbial production platforms, such as bacteria and yeasts, as well as to create pre-optimized chassis host strains. However, the complexity of mammalian cells curtailed the optimization of these host cells by metabolic engineering. Most of the improvements of titer and productivity were achieved by media optimization and large-scale screening of producer clones. The advances made in recent years now open the door to again consider the potential application of systems biology approaches and metabolic engine... [more]

In this study, magnetic Fe3O4 nanoparticles coated with polydopamine possessing abundant amino groups (Fe3O4@PDA) were conveniently prepared, detailed, and characterized, and then firstly used as a supporting matrix for immobilizing Thermomyces lanuginosus lipase (Fe3O4@PDA@TLL). The effects of some crucial factors on the immobilization efficiency were investigated and the optimal protein loading and activity recovery were found to be 156.4 mg/g and 90.9%, respectively. Characterization studies revealed that Fe3O4@PDA@TLL displayed a broader pH and temperature adaptability as compared to the free TLL, which allows its use at wider ranges of reaction conditions. With regard to the stabilities, the immobilized TLL clearly displayed improved pH, thermal, and solvent tolerance stabilities compared to the free enzyme, suggesting that the biocompatible Fe3O4@PDA might be an outstanding material for immobilizing TLL and acting as alternative support for different enzymes.

The unique pool of features found in intracellular and extracellular bacterial biopolymers attracts a lot of research, with bacterial cellulose (BC) being one of the most versatile and common. BC is an exopolysaccharide consisting solely of cellulose, and the variation in the production process can vary its shape or even its composition when compounding is applied in situ. Together with ex situ modification pathways, including specialised polymers, particles or exclusively functional groups, BC provides a robust platform that yields complex multifunctional compounds that go far beyond ultra-high purity, intrinsic hydrophilicity, mechanical strength and biocompatibility to introduce bioactive, (pH, thermal, electro) responsive, conductive and ‘smart’ properties. This review summarises the research outcomes in BC-medical applications, focusing mainly on data from the past decade (i.e., 2010−2020), with special emphasis on BC nanocomposites as materials and devices applicable in medicine.... [more]

A class of drugs called coxibs (COX-2 inhibitors) were created to help relieve pain and inflammation of osteoarthritis and rheumatoid arthritis with the lowest amount of side effects possible. The presented paper describes a new developed, optimized and validated thin layer chromatographic (TLC)-densitometric procedure for the simultaneous assay of five coxibs: celecoxib, etoricoxib, firecoxib, rofecoxib and cimicoxib. Chromatographic separation was conducted on HPTLC F254 silica gel chromatographic plates as a stationary phase using chloroform−acetone−toluene (12:5:2, v/v/v) as a mobile phase. Densitometric detection was carried out at two wavelengths of 254 and 290 nm. The method was tested according to ICH guidelines for linearity, recovery and specificity. The presented method was linear in a wide range of concentrations for all analyzed compounds, with correlation coefficients greater than 0.99. The method is specific, precise (%RSD < 1) and accurate (more than 95%, %RSD < 2... [more]

Bioactive glass scaffolds are used in bone and tissue biomedical implants, and there is great interest in their fabrication by additive manufacturing/3D printing techniques, such as robocasting. Scaffolds need to be macroporous with voids ≥100 m to allow cell growth and vascularization, biocompatible and bioactive, with mechanical properties matching the host tissue (cancellous bone for bone implants), and able to dissolve/resorb over time. Most bioactive glasses are based on silica to form the glass network, with calcium and phosphorous content for new bone growth, and a glass modifier such as sodium, the best known being 45S5 Bioglass®. 45S5 scaffolds were first robocast in 2013 from melt-quenched glass powder. Sol−gel-synthesized bioactive glasses have potential advantages over melt-produced glasses (e.g., greater porosity and bioactivity), but until recently were never robocast as scaffolds, due to inherent problems, until 2019 when high-silica-content sol−gel bioactive glasses (H... [more]

Aquatic pollution caused by industrial effluents is an environmental issue, imposing deleterious impacts on the overall environment, specifically, on humans, by disrupting the balance of the ecosystem. Among all the industries, tanneries are considered some of the most polluting due to heavy use of toxic organic and inorganic compounds during leather processing, most of which find their way into rivers, lakes, and streams, thus exerting adverse effects on aquatic life, particularly on fish. Considering the huge concentrations of pollutants present in tannery effluents, toxicity evaluation is of prime importance. Therefore, bioassays are usually employed to assess the acute toxicity of industrial effluents and efficiency of effluent clean-up technologies as they provide a thorough response of test species to the substances present in the tested media. In the present study, the toxic effects of tannery effluent on common grass carp (Ctenopharyngodon idella) were studied for 96 h in labor... [more]

The transitioning of carbon quantum dot (cQD) applications from electrochemistry, catalysis and environmental sensing to biomedicine represents an important milestone in its 15-year history; a bellwether for its yet-unrealized potential in interventional biology, imaging, diagnostics, prophylaxis and therapy. However, despite the significant advances made over the last decade in several areas of the cQD domain, our knowledge of the exact chemical ipseity of cQDs at the Angstrom level remains either in its infancy or is largely ignored. The imminent crossing over of cQDs into biological systems and into the blood−brain barrier demands attention to the critical, yet unmet, need to resolve the inherent heterogeneity in cQD preparations and their separation into purified conformers, to identify the issues associated with potential cytotoxicity as well as to examine their bioavailability. Perhaps most importantly, and ironically neglected as well, is the compelling urgency to obtain an atom... [more]

Ensuring high quality drinking water sources is important task nowadays. To reach this task, knowledge about the impact of different chemicals on aerobic wastewater treatment is mandatory. A mixture of different chemicals reaches wastewater treatment plant every day. With the growing discharge volume of mobile toilet chemicals, active substances in these products in the past years have been recorded. The respiratory activity of activated sludge was determined to show how mobile toilet chemicals and their active substances may affect the biological wastewater treatment process. The results show negative effect of formaldehyde and bronopol on respiratory activity of activated sludge. The wastewater treatment plants influent composition and size also play important roles. Results shows that activated sludge microorganisms at a wastewater treatment plant in industrial urban area may be adapted to the higher pollutants concentration. When mobile toilet tanks are directly discharged at small... [more]

Emissions from daily and final covers of municipal solid waste (MSW) landfills can produce significant impacts on local and global environments. Simplifying, landfills can cause local impacts with odor emissions and global impacts with GHGs. This work focuses on hydrogen sulfide (H2S) and methane (CH4) emissions, with the aim of studying how it is possible to reduce their impacts by means of biofiltration systems. Both field and laboratory investigations have been carried out in Casa Rota Landfill (Tuscany, Italy). In the field trials, four pilot-scale biocovers made of compost from a source-selected organic fraction (SS compost), compost from a mechanical biological treatment plant—the residual fractions of the MSW, a mixed compost (SS-MSW compost) and sand were monitored in the daily cover area of the landfill, where high emissions were detected. Results showed that high CH4 and H2S emissions reductions occurred in the mixed SS-MSW compost plot, given a maximum methane oxidation effi... [more]

Ajmalicine is one of the most popular antihypertensive drugs obtained from the root barks of Cathranthus roseus (L.) G. Don and Rauvolfia serpentine (L.) Benth. ex Kurz. It has also potential antimicrobial, cytotoxic, central depressant and antioxidant activities. As the demand for the alkaloid is significantly high, metabolic engineering approaches are being tried to increase its production in both homologous and heterologous systems. The metabolic engineering approach requires knowledge of the metabolic regulation of the alkaloid. For understanding the metabolic regulation, fluxomic analysis is important as it helps in understanding the flux of the alkaloid through the complicated metabolic pathway. The present study was conducted to analyse the flux analysis of the ajmalicine biosynthesis, using a genetically encoded Fluorescent Resonance Energy Transfer FRET-based nanosensor for ajmalicine (FLIP-Ajn). Here, we have silenced six important genes of terpenoid indole alkaloid (TIA), na... [more]