1. The Role and Functioning of the OECD 2. Sustainable Management of Resources 2.1 Waste Management 2.2 Biodiversity 3. Protection of Health and Safety 3.1 Testing of Chemicals 3.2 Good Laboratory Practice 3.3 Mutual Acceptance of Data 3.4 High Production Volume Chemicals 4. Climate Change 4.1 Energy Efficiency 4.2 Environmentally Sustainable Transport 5. Biotechnology 5.1 Human Health 5.2 Agriculture and Food 5.3 Environmental and Industrial Applications 6. Conclusion Glossary Bibliography Biographical Sketch
Enis Ben Bnina, Jihen Missaoui, Mohamed Firas Gannouni
et al.
Food safety and control are fundamental public health issues that maintain consumer confidence and protection. This design (management) requires monitoring production, processing, and conservation processes while limiting microbiological, chemical, and physical risks. In this context, clove essential oil, a bioactive essence with a broad spectrum of biological activities, is increasingly studied as a natural biopreservative in innovative food safety strategies. This study reports the encapsulation of this oil into a nanoemulsion at concentrations of 10 mg/mL, 1 mg/mL, and 0.1 mg/mL. Dynamic light scattering, zeta potential, polydispersity index, and particle size all demonstrated optimal morphology and a stable system.The nanoformulation significantly improves the antioxidant activity of clove essential oil, even at high dilutions, while protecting the degradation of natural active ingredients and ensuring controlled release. This nanoemulsion exhibits a moderate antimicrobial effect against various resistant pathogenic bacteria and fungi. However, at a concentration of 10 mg/mL, it showed a 100 % antibiofilm effect against both Gram-positive and Gram-negative bacteria. This nanoemulsion demonstrated significant potential to prevent surface adhesion against all bacteria tested, except L. monocytogenes.This research reveals crucial information about an innovative natural nanoemulsion for food safety and control, unveiling its antioxidant, anti-adhesive, and anti-biofilm potential against resistant pathogens. These results represent a promising step forward in reducing contamination risks and extending shelf life without altering organoleptic properties, offering environmental benefits and hygiene practices while targeting sustainable industrial applications to increase food safety.
Xiaoyue Shang, Nina Bartels, Johann Moritz Weck
et al.
Abstract Background Cluster of differentiation 95 (CD95/Fas/Apo1) as part of the Tumor-necrosis factor (TNF) receptor family is a prototypic trigger of the ‘extrinsic’ apoptotic pathway and its activation by the trimeric ligand CD95L is of high interest. However, CD95L, when presented in solution, exhibits a low efficiency to induce apoptosis signaling in human cells. Results Here, we design a recombinant CD95L exhibiting an isoleucine zipper (IZ) motif at the N-terminus for stabilization of the trimerized CD95L and demonstrate its high apoptosis initiation efficiency. This efficiency is further enhanced by antibody-mediated crosslinking of IZ-CD95L.A cysteine amino acid fused behind the IZ is used as a versatile coupling site for bionanotechnological applications or for the development of biomedical assays. A fast, cheap, and efficient production of CD95L via the HEK293T secretory expression system is presented, along with CD95L affinity purification and functionalization. We verified the biological activity of the purified protein and identified a stabilized trimeric CD95L structure as the most potent inducer of apoptosis signaling. Conclusions The workflow and the findings reported here will streamline a wide array of future low- or high-throughput TNF-ligand screens, and their modification towards improving apoptosis induction efficiency and, potentially, anticancer therapy.
Abstract Background Fipronil (FPN) is a broad-spectrum pesticide and commonly known as low toxicity to vertebrates. However, increasing evidence suggests that exposure to FPN might induce unexpected adverse effects in the liver, reproductive, and nervous systems. Until now, the influence of FPN on immune responses, especially T-cell responses has not been well examined. Our study is designed to investigate the immunotoxicity of FPN in ovalbumin (OVA)-sensitized mice. The mice were administered with FPN by oral gavage and immunized with OVA. Primary splenocytes were prepared to examine the viability and functionality of antigen-specific T cells ex vivo. The expression of T cell cytokines, upstream transcription factors, and GABAergic signaling genes was detected by qPCR. Results Intragastric administration of FPN (1–10 mg/kg) for 11 doses did not show any significant clinical symptoms. The viability of antigen-stimulated splenocytes, the production of IL-2, IL-4, and IFN-γ by OVA-specific T cells, and the serum levels of OVA-specific IgG1 and IgG2a were significantly increased in FPN-treated groups. The expression of the GABAergic signaling genes was notably altered by FPN. The GAD67 gene was significantly decreased, while the GABAR β2 and GABAR δ were increased. Conclusion FPN disturbed antigen-specific immune responses by affecting GABAergic genes in vivo. We propose that the immunotoxic effects of FPN may enhance antigen-specific immunity by dysregulation of the negative regulation of GABAergic signaling on T cell immunity.
Liselot Dewachter, Babette Deckers, Israel Mares-Mejía
et al.
Abstract During growth, cells need to synthesize and expand their envelope, a process that requires careful regulation. Here, we show that the GTPase ObgE of E. coli contributes to the regulation of lipopolysaccharide (LPS) synthesis, an essential component of the Gram-negative outer membrane. Using a dominant-negative mutant (named ‘ObgE*’), we show a direct interaction between ObgE and LpxA, which catalyzes the first step in LPS synthesis. This interaction is enhanced by the mutation in ObgE* which, when bound to GTP, leads to inhibition of LpxA, decreased LPS synthesis, and cell death. Although wild-type ObgE does not exert the same strong effects as ObgE* on LpxA or LPS synthesis, our data indicate that ObgE participates in the regulation of cell envelope synthesis in E. coli. Because ObgE also influences other cellular functions (i.e., ribosome assembly, DNA replication, etc.), it seems increasingly plausible that this GTPase coordinates several processes to finetune cell growth.
Sahar Farajnia, Nazli Khajenasiri, Safar Farajnia
et al.
Introduction: Despite the efforts to contain the spread of COVID-19, the virus remains in circulation, posing a considerable risk to populations across the globe. Hence, rapid and early detection of this infection is essential for effective disease control. The nucleocapsid (N) protein of the virus serves as a primary target for antibody response during CoV2 infections, making it a potential candidate for COVID-19 detection. This study aims to prepare and evaluate the linear epitopes of the N protein for serodiagnosis of COVID-19 infection. Methods: The linear epitope of the N protein gene was identified using ABCpred, BCpred, and IEDB. These epitopes were subsequently amplified by RT-PCR, cloned, and expressed in soluble form in the E. coli BL21 strain. The recombinant protein was purified using the Ni-NTA column. The reactivity of purified N protein with sera from SARS-CoV-2 patients was analyzed using an ELISA assay. Results: Sequencing analysis demonstrated the successful cloning of the linear epitopes of the N protein into the PET-28a vector, along with an n-terminal His-tag fusion. The recombinant protein was produced in E. coli BL21 and purified with a Ni-NTA column. The analysis demonstrated that the N protein linear epitopes were expressed in a soluble form and appeared as a 50 kDa band in the SDS-PAGE. Examination for the reactivity of the purified N protein with the COVID-19 patient’s sera by ELISA revealed that the N protein recognizes the infection with high sensitivity and specificity. Conclusion: The results of this study indicated that linear epitopes of the SARS-CoV-2 N protein are highly immunogenic and could be exploited for serodiagnosis of infection in patients suspected of COVID-19 infection.
Abstract Background Streptococcus iniae is an important fish pathogen that cause significant economic losses to the global aquaculture industry every year. Although there have some reports on the genotype of S.iniae and its relationship with virulence, no genome-scale comparative analysis has been performed so far. In our previous work, we characterized 17 isolates of S.iniae from Trachinotus ovatus and divided them into two genotypes using RAPD and rep-PCR methods. Among them, BH15-2 was classified as designated genotype A (in RAPD) and genotype 1 (in rep-PCR), while BH16-24 was classified as genotype B and genotype 2. Herein, we compared the differences in growth, drug resistance, virulence, and genome between BH15-2 and BH16-24. Results The results showed that the growth ability of BH16-24 was significantly faster than that of BH15-2 at the exponential stage. Antimicrobial tests revealed that BH15-2 was susceptible to most of the tested antibiotics except neomycin and gentamycin. In contrast, BH16-24 was resistant to 7 antibiotics including penicillin, sulfasomizole, compound sulfamethoxazole tablets, polymyxin B, spectinomycin, rifampin and ceftazidime. Intraperitoneal challenge of T.ovatus, showed that the LD50 value of BH15-2 was 4.0 × 102 CFU/g, while that of BH16-24 was 1.2 × 105 CFU/g. The genome of S.iniae BH15-2 was 2,175,659 bp with a GC content of 36.80%. Meanwhile, the genome of BH16-24 was 2,153,918 bp with a GC content of 36.83%. Comparative genome analysis indicated that compared with BH15-2, BH16-24 genome had a large-scale genomic inversion fragment, at the location from 502,513 bp to 1,788,813 bp, resulting in many of virulence and resistance genes differentially expression. In addition, there was a 46 kb length, intact phage sequence in BH15-2 genome, which was absent in BH16-24. Conclusion Comparative genomic studies of BH15-2 and BH16-24 showed that the main difference is a 1.28 Mbp inversion fragment. The inversion fragment may lead to abnormal expression of drug resistant and virulence genes, which is believed to be the main reason for the multiple resistance and weakened virulence of BH16-24. Our study revealed the potential mechanisms in underlying the differences of multidrug resistance and virulence among different genotypes of S.iniae.
Rano Mamadalieva, Vahobjon Khujaev, Michal Šoral
et al.
The genus <i>Allochrusa</i> (Caryophyllaceae) comprises nine species, which are native to Central Asia, Turkey, Iran, Afghanistan, and the Caucasus. They have been used in folk medicine and in the preparation of various sweets and detergents, especially in Asian countries. A diversity of secondary metabolites has been reported from the genus <i>Allochrusa</i>, including triterpene glycosides, ecdysteroids, flavonoids, volatile compounds, fatty acids, polysaccharides, pectins, hemicelluloses, and other phytochemicals. In vitro and in vivo pharmacological studies on isolated compound fractions and extracts from <i>Allochrusa</i> species showed anti-inflammatory, adjuvant, hemolytic, cytotoxic, antifungal, analgesic, antioxidant, and other activities. In this review, the chemical compounds and diverse biological activities of the <i>Allochrusa</i> genus are summarized.
Víctor Gutiérrez-González, Gisela Gerardi, Pilar Muñiz
et al.
Hyperglycemia is a significant risk factor in metabolic syndrome, contributing to the development of cardiovascular diseases and diabetes mellitus. Hyperglycemia increases ROS (reactive oxygen species) production via glucose oxidation and protein glycosylation, leading to cell damage. Our previous studies have highlighted the antioxidant properties of wine pomace products (wWPPs), a co-product of winemaking, and their ability to modulate oxidative stress. The objective of this study was to evaluate the protective effect of wWPPs against oxidative stress in hyperglycemic Caco-2 cells. They were treated with 1.5 μg GAE/mL of wWPP bioaccessible fractions, obtained from gastrointestinal digestion (WPGI) and colonic fermentation (WPF), under normoglycemic or hyperglycemic (35 mM glucose) conditions. After 24 h of treatment, cell viability, oxidative stress biomarkers and the expression of transcription factors and enzymes involved in cellular oxidation balance were evaluated. Hyperglycemia induced a 30% reduction in cell viability, which was restored to normoglycemic levels by WPF treatment. The bioaccessible fractions were able to counteract hyperglycemia-induced oxidative stress in intestinal cells, as evidenced by significant decreases in carbonyl groups and MDA levels (10 and 40%, respectively). Furthermore, hyperglycemia-induced NF-κB overexpression was also significantly reduced by WPGI and WPF pre-treatment (between 15 and 53%), modulating the redox activity. In conclusion, the bioaccessible fractions of wWPP, particularly WPF, demonstrated significant potential in mitigating hyperglycemia-induced oxidative stress and enhancing cell viability in Caco-2 cells.
Haider Turky Mousa Al-Mousawi , Alia Hussein Ali, Nadhim Hashim
Cigarette smoking currently is considered as one of the greatest problems in public health worldwide and is risk factor for peripheral vascular disorders and heart disease. The monitoring of liver function and total cholesterol are very important to give an estimation of the future cardiovascular diseases among smokers. The objective of this study is to evaluate the effect of cigarette smoking on the serum levels of liver enzymes: aspartate aminotransferase (GOT), alanine transaminase (GPT) and cholesterol activities among Iraqi smokers in Babylon City, compared to apparently healthy individuals (non-smokers) as a control group (all were males). A case- control study was carried out on forty Iraqi male smokers who smoke at least 10 cigarettes per day for at least15 years. The group includes smokers with age range between 15-55 years. Non-smokers, (control, n= 20) group were collected with the same range of age for statistical comparison. The whole blood samples were drawn by venipuncture from each individual; levels of cholesterol and liver functions test were estimated in the blood serum of smokers and non-smokers by diagnostic kit (Randox corporation-UK) using automatic analyzer.The findings of this study showed that there was a significant higher level of total cholesterol, ALT, and AST in the smokers group compared to non-smokers (P<0.05). As well as, the results showed a significant positive correlation between the smokers’ age and serum GOT, GPT and cholesterol activity (Increasing) especially in age between 45 to 55 years old, as compared to control. In addition, total cholesterol and liver function enzymes were significantly positive correlated with the duration of smoking (P<0.05).Cigarette smoking leads to oxidative stress by free radical generation by the mechanism of lipid peroxidation that is affected by the heaviness of smoking. Smoking exerts negative influence on liver functions test that should be carefully interpreted and preventive strategies needed to avoid the future cardiovascular diseases.
Muhammad Umair, Muhammad Younus, Sarfraz Shafiq
et al.
Spondylocostal dysostosis is a genetic defect associated with severe rib and vertebrae malformations. In recent years, extensive clinical and molecular diagnosis advancements enabled us to identify disease-causing variants in different genes for such severe conditions. The identification of novel candidate genes enabled us to understand the developmental biology and molecular and cellular mechanisms involved in the etiology of these rare diseases. Here, we discuss the clinical and molecular targets associated with spondylocostal dysostosis, including clinical evaluation, genes, and pathways involved. This review might help us understand the basics of such a severe disorder, which might help in proper clinical characterization and help in future therapeutic strategies.
BackgroundNeutropenia and cytokine release syndrome (CRS) are two major toxicities of chimeric antigen receptor (CAR)-T cell therapy. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is an ideal candidate treatment for neutropenia except for its potential aggravation of CRS. We hypothesized that the optimal timing of supplemental with GM-CSF in a shortage of host immunity and CAR T-cell was chosen as avoidance of CRS. In the study we evaluated the safety and efficacy of GM-CSF intervention post-CAR T-cell therapy while circulating CAR T-cell declined.Materials and methodsNine patients received GM-CSF therapy who displayed moderate neutropenia with absolute neutrophil counts (ANC) < 1,500 cells/mm3 with concomitant declination of circulating CAR T-cell.ResultsThe median duration of GM-CSF intervention was 15 days (4–30). CAR T-cell expansion was observed in peripheral blood (PB) of seven patients (7/9). The median baseline and peak CAR T cells count in PB of the seven patients with CAR T-cell expansion were 0.85 × 106/L (0–50.9) and 6.06 × 106/L (1.43–112.55). And the peaks of CAR T-cell levels in PB appeared in day 7 (2–11) following the initiation of GM-CSF administration with increases of 2.84 × 106/L (0.38–61.65). Also, increased white blood cells in PB were observed in all patients. The median onset and duration time of WBC recovery were 9 (1–14) and 17 (3–53) days. Moreover, the increment of WBC, neutrophil, lymphocyte and CD3-CD16 + CD56 + natural killer cell in PB was observed. In addition, no CRS or fatal infection occurred during GM-CSF treatment.ConclusionThis study provides evidence for the clinical feasibility of combining CAR T-cell therapy with the GM-CSF to treat neutropenia patients with concomitant declination of circulating CAR T-cell.
The selection of restorative materials with regard to the longevity and durability of a restoration is of crucial importance for daily dental practice and requires that the degradation of the material in the oral environment can be assessed. The aim of this study was to investigate the extent to which the mechanical properties of four (Esthet X, Ceram X, Filtek Supreme XT, and Filtek Supreme XT flow) resin-based composites (RBCs) alter during storage in saliva substitutes (artificial saliva) for 24 h and 28 days and in the context of simulated, more aggressive clinical conditions, including cycles exposure to de- and remineralization, alcohol, or salivary enzymes. For this purpose, flexural strength and modulus were determined in a three-point bending test (<i>n</i> = 20) followed by Weibull analysis, while quasi-static behavior was evaluated by instrumented indentation techniques. Degradation occurred in all RBCs and all aging protocols and was quantifiable at both macroscopic and microscopic levels. The postulated stabilizing effect on degradation through the incorporation of urethane-based co-monomers into the organic matrix or a higher filler loading is refuted. Even though modern RBCs show high clinical survival rates, biodegradation remains an issue that needs to be addressed.
Philippe Sucosky, Varun Vinayak Kalaiarasan, Graham B. Quasebarth
et al.
Abstract Long-duration spaceflight poses multiple hazards to human health, including physiological changes associated with microgravity. The hemodynamic adaptations occurring upon entry into weightlessness have been associated with retrograde stagnant flow conditions and thromboembolic events in the venous vasculature but the impact of microgravity on cerebral arterial hemodynamics and function remains poorly understood. The objective of this study was to quantify the effects of microgravity on hemodynamics and wall shear stress (WSS) characteristics in 16 carotid bifurcation geometries reconstructed from ultrasonography images using computational fluid dynamics modeling. Microgravity resulted in a significant 21% increase in flow stasis index, a 22–23% decrease in WSS magnitude and a 16–26% increase in relative residence time in all bifurcation branches, while preserving WSS unidirectionality. In two anatomies, however, microgravity not only promoted flow stasis but also subjected the convex region of the external carotid arterial wall to a moderate increase in WSS bidirectionality, which contrasted with the population average trend. This study suggests that long-term exposure to microgravity has the potential to subject the vasculature to atheroprone hemodynamics and this effect is modulated by subject-specific anatomical features. The exploration of the biological impact of those microgravity-induced WSS aberrations is needed to better define the risk posed by long spaceflights on cardiovascular health.
Rheumatoid arthritis (RA) is a widespread chronic autoimmune disorder affecting the joints, causing irreversible cartilage, synovium, and bone degradation. During the course of the disease, many immune and joint cells are activated, causing inflammation. Immune cells including macrophages, lymphocytes, neutrophils, mast cells, natural killer cells, innate lymphoid cells, as well as synovial tissue cells, like fibroblast-like synoviocytes, chondrocytes, and osteoclasts secrete different proinflammatory factors, including many cytokines, angiogenesis-stimulating molecules and others. Recent studies reveal that curcumin, a natural dietary anti-inflammatory compound, can modulate the response of the cells engaging in RA course. This review comprises detailed data about the pathogenesis and inflammation process in rheumatoid arthritis and demonstrates scientific investigations about the molecular interactions between curcumin and immune cells responsible for rheumatoid arthritis development to discuss this herbal drug’s immunoregulatory role in RA treatment.
Houston J. Saxe, Takanori Horibe, Bipin Balan
et al.
We showed previously that gallic acid is produced in walnut from 3-dehydroshikimate by a shikimate dehydrogenase (JrSkDH). This study focuses on the next step in the hydrolysable tannin pathway, the formation of 1-O-galloyl-β-D-glucose from the phenolic gallic acid and UDP glucose by a glycosyltransferase. JrGGT1 (UGT84A73) and JrGGT2 (UGT84A74) are predicted to be two such glycosyltransferases, which we expressed in tobacco plants. GC-MS analysis of the transgenic tobacco revealed moderate, yet significant alterations in plant secondary metabolism, such as depleted phenolic acids, including gallic acid. We postulate that these effects are due to JrGGT1 and JrGGT2 activity, as JrGGT orthologs glycosylate these phenolic compounds in vitro. Moreover, JrGGT expression in tobacco caused upregulation of shikimic acid pathway metabolites and differing responses in phenylpropanoids, such as phenolic acids and flavonoids. In transcriptome analysis of walnut pellicle tissues, both JrGGTs showed substantial and significant expression correlations with the gallic acid-producing JrSkDHs and were highly coexpressed with the genetic circuits constituting the shikimic acid and phenylpropanoid biosynthetic pathways. Verification of JrGGT gene expression by transcriptome analysis of 20 walnut tissues revealed striking similarities with that of the pellicle data, with the greatest expression in roots, wood, buds, and leaves of Juglans regia cv. Chandler: tissues that typically accumulate hydrolysable tannins. Like the transgenic tobacco, pellicle metabolomic analyses revealed that many phenylpropanoids correlated negatively with JrGGT expression, while shikimic acid pathway metabolites correlated positively with JrGGT expression. This research supports the hypothesis that JrGGT1 and JrGGT2 play non-trivial roles in metabolism of phenolic acids, flavonoids, and ostensibly, tannins.