Effect of Modified Bioceramic Mineral Trioxide Aggregate Cement with Mesoporous Nanoparticles on Human Gingival Fibroblasts.

The ion doping of mesoporous silica nanoparticles (MSNs) has played an important role in revolutionizing several materials applied in medicine and dentistry by enhancing their antibacterial and regenerative properties. Mineral trioxide aggregate (MTA) is a dental material widely used in vital pulp therapies with high success rates. The aim of this study was to investigate the effect of the modification of MTA with cerium (Ce)- or calcium (Ca)-doped MSNs on the biological behavior of human gingival fibroblasts (hGFs). MSNs were synthesized via sol-gel, doped with Ce and Ca ions, and mixed with MTA at three ratios each. Powder specimens were characterized using Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and scanning electron microscopy (SEM). Biocompatibility was evaluated using a 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay following hGFs' incubation in serial dilutions of material eluates. Antioxidant status was evaluated using Cayman's antioxidant assay after incubating hGFs with material disc specimens, and cell attachment following dehydration fixation was observed through SEM. Material characterization confirmed the presence of mesoporous structures. Biological behavior and antioxidant capacity were enhanced in all cases with a statistically significant increase in CeMTA 50.50. The application of modified MTA with cerium-doped MSNs offers a promising strategy for vital pulp therapies.

Synthesis and Characterization of Mesoporous Mg- and Sr-Doped Nanoparticles for Moxifloxacin Drug Delivery in Promising Tissue Engineering Applications.

Mesoporous silica-based nanoparticles (MSNs) are considered promising drug carriers because of their ordered pore structure, which permits high drug loading and release capacity. The dissolution of Si and Ca from MSNs can trigger osteogenic differentiation of stem cells towards extracellular matrix calcification, while Mg and Sr constitute key elements of bone biology and metabolism. The aim of this study was the synthesis and characterization of sol-gel-derived MSNs co-doped with Ca, Mg and Sr. Their physico-chemical properties were investigated by X-ray diffraction (XRD), scanning electron microscopy with energy dispersive X-ray analysis (SEM/EDX), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), X-ray fluorescence spectroscopy (XRF), Brunauer Emmett Teller and Brunauer Joyner Halenda (BET/BJH), dynamic light scattering (DLS) and ζ-potential measurements. Moxifloxacin loading and release profiles were assessed with high performance liquid chromatography (HPLC) cell viability on human periodontal ligament fibroblasts and their hemolytic activity in contact with human red blood cells (RBCs) at various concentrations were also investigated. Doped MSNs generally retained their textural characteristics, while different compositions affected particle size, hemolytic activity and moxifloxacin loading/release profiles. All co-doped MSNs revealed the formation of hydroxycarbonate apatite on their surface after immersion in simulated body fluid (SBF) and promoted mitochondrial activity and cell proliferation.

Oxidation of Erythrocytes Enhance the Production of Reactive Species in the Presence of Artemisinins.

In red blood cells, hemoglobin iron represents the most plausible candidate to catalyze artemisinin activation but the limited reactivity of iron bound to hemoglobin does not play in favor for its direct involvement. Denatured hemoglobin appears a more likely candidate for artemisinin redox activation because it is expected to contain reactive iron and it has been described to release free heme and/or iron in erythrocyte. The aim of our study is to investigate, using three different methods: fluorescence, electron paramagnetic resonance and liquid chromatography coupled to mass spectrometry, how increasing the level of accessible iron into the red blood cells can enhance the reactive oxygen species (ROS) production derived from artemisinin. The over-increase of iron was achieved using phenylhydrazine, a strong oxidant that causes oxidative stress within erythrocytes, resulting in oxidation of oxyhemoglobin and leading to the formation of methemoglobin, which is subsequently converted into irreversible hemichromes (iron (III) compounds). Our findings confirmed, using the iron III chelator, desferrioxamine, the indirect participation of iron (III) compounds in the activation process of artemisinins. Furthermore, in strong reducing conditions, the activation of artemisinin and the consequent production of ROS was enhanced. In conclusion, we demonstrate, through the measurement of intra-erythrocytic superoxide and hydrogen peroxide production using various methods, that artemisinin activation can be drastically enhanced by pre-oxidation of erythrocytes.

Syk Inhibitors: New Computational Insights into Their Intraerythrocytic Action in Plasmodium falciparum Malaria.

Resistance to antimalarial drugs has spread rapidly over the past few decades. The WHO recommends artemisinin-based combination therapies for the treatment of uncomplicated malaria, but unfortunately these approaches are losing their efficacy in large areas of Southeast Asia. In 2016, artemisinin resistance was confirmed in 5 countries of the Greater Mekong subregion. We focused our study on Syk inhibitors as antimalarial drugs. The Syk protein is present in human erythrocytes, and the membrane of protein band 3 is its major target following activation by oxidant stress. Tyr phosphorylation of band 3 occurs during P. falciparum growth, leading to the release of microparticles containing hemicromes and structural weakening of the host cell membrane, simplifying merozoite reinfection. Syk inhibitors block these events by interacting with the Syk protein's catalytic site. We performed in vitro proteomics and in silico studies and compared the results. In vitro studies were based on treatment of the parasite's cellular cultures with different concentrations of Syk inhibitors, while proteomics studies were focused on the Tyr phosphorylation of band 3 by Syk protein with the same concentrations of drugs. In silico studies were based on different molecular modeling approaches in order to analyze and optimize the ligand-protein interactions and obtain the highest efficacy in vitro. In the presence of Syk inhibitors, we observed a marked decrease of band 3 Tyr phosphorylation according to the increase of the drug's concentration. Our studies could be useful for the structural optimization of these compounds and for the design of novel Syk inhibitors in the future.

Syk inhibitors interfere with erythrocyte membrane modification during P falciparum growth and suppress parasite egress.

Band 3 (also known as the anion exchanger, SLCA1, AE1) constitutes the major attachment site of the spectrin-based cytoskeleton to the erythrocyte's lipid bilayer and thereby contributes critically to the stability of the red cell membrane. During the intraerythrocytic stage of Plasmodium falciparum's lifecycle, band 3 becomes tyrosine phosphorylated in response to oxidative stress, leading to a decrease in its affinity for the spectrin/actin cytoskeleton and causing global membrane destabilization. Because this membrane weakening is hypothesized to facilitate parasite egress and the consequent dissemination of released merozoites throughout the bloodstream, we decided to explore which tyrosine kinase inhibitors might block the kinase-induced membrane destabilization. We demonstrate here that multiple Syk kinase inhibitors both prevent parasite-induced band 3 tyrosine phosphorylation and inhibit parasite-promoted membrane destabilization. We also show that the same Syk kinase inhibitors suppress merozoite egress near the end of the parasite's intraerythrocytic lifecycle. Because the entrapped merozoites die when prevented from escaping their host erythrocytes and because some Syk inhibitors have displayed long-term safety in human clinical trials, we suggest Syk kinase inhibitors constitute a promising class of antimalarial drugs that can suppress parasitemia by inhibiting a host target that cannot be mutated by the parasite to evolve drug resistance.

Hematological, biochemical and antioxidant indices variations in regular blood donors among Mediterranean regions.

BACKGROUND & OBJECTIVES: One of the most important problems in Mediterranean regions is finding blood donors to overcome the high need of its population. Understanding the health benefits of blood donation frequency will activate more volunteers to donate. The aim of this study variations of hematological and biochemical indices in regular male and female donors from Greece and Italy METHODS: A cross-sectional study consisted of 350 voluntary blood donors (VDs)was conducted in two mediterranean Blood Banks, Greece and Italy. The first one from the General Hospital of Naousa, Greece on samples of 90 regular and 60 first-time blood donors. The second one from AOU Sassari, Sardinia, Italy on convenient samples of 100 first-time samples and 100 regular blood donors. Donors' particulars were obtained from blood bank records. The hematological and biochemical parameters were determined for all donors and Total Antioxidant Status (TAS) only for greek VDs. RESULTS: High frequency blood donation of Greek VDs could be associated with evidence of reduction of body iron stores, reduced oxidative stress and improvement of liver function biomarkers in regular groups. Interestingly, Sardinian regular male VDs presented increased iron stores in compare with the first time VDs. In both Mediterranean populations (Greeks and Italians) the lipid profile of the female regular blood donors has been improved in compare with the first timers. CONCLUSION: Regular blood donation increases antioxidant capacity and affects positively the hematological parameters and biochemical biomarkers in donors. Gender plays an important role in relation to all hematological and biochemical parameters. Further studies in larger population should evaluate the beneficial-effect of blood donation and promote people to donate more frequent.

Effect of ethanol/TEOS ratios and amount of ammonia on the properties of copper-doped calcium silicate nanoceramics.

Calcium magnesium silicate glasses could be suggested for the synthesis of scaffolds for hard tissue regeneration, as they present a high residual glassy phase, high hardness values and hydroxyapatite-forming ability. The use of trace elements in the human body, such as Cu, could improve the biological performance of such glasses, as Cu is known to play a significant role in angiogenesis. Nano-bioceramics are preferable compared to their micro-scale counterparts, because of their increased surface area, which improves both mechanical properties and apatite-forming ability due to the increased nucleation sites provided, their high diffusion rates, reduced sintering time or temperature, and high mechanical properties. The aim of the present work was the evaluation of the effect of different ratios of Ethanol/TEOS and total amount of the inserted ammonia to the particle size, morphology and bioactive, hemolytic and antibacterial behavior of nanoparticles in the quaternary system SiO2-CaO-MgO-CuO. Different ratios of Ethanol/TEOS and ammonia amount affected the size and morphology of bioactive nanopowders. The optimum materials were synthesized with the highest ethanol/TEOS ratio and ammonia amount as verified by the enhanced apatite-forming ability and antibacterial and non-hemolytic properties.

Effect of silica-based mesoporous nanomaterials on human blood cells.

Different mesoporous nanomaterials (MSNs) are constantly being developed for a range of therapeutic purposes, but they invariably interact with blood components and may cause hazardous side effects. Therefore, when designing and developing nanoparticles for biomedical applications, hemocompatibility should be one of the primary goals to assess their toxicity at the cellular level of all blood components. The aim of this study was to evaluate the compatibility of human blood cells (erythrocytes, platelets, and leukocytes) after exposure to silica-based mesoporous nanomaterials that had been manufactured using the sol-gel method, with Ca and Ce as doping elements. The viability of lymphocytes and monocytes was unaffected by the presence of MSNs at any concentration. However, it was found that all nanomaterials, at all concentrations, reduced the viability of granulocytes. P-selectin expression of all MSNs at all concentrations was statistically significantly higher in platelet incubation on the first day of storage (day 1) compared to the control. When incubated with MSNs, preserved platelets displayed higher levels of iROS at all MSNs types and concentrations examined. Ce-containing MSNs presented a slightly better hemocompatibility, although it was also dose dependent. Further research is required to determine how the unique characteristics of MSNs may affect various blood components in order to design safe and effective MSNs for various biomedical applications.

Αnti-prion effects of anthocyanins.

Prion diseases, also known as Transmissible Spongiform Encephalopathies (TSEs), are protein-based neurodegenerative disorders (NDs) affecting humans and animals. They are characterized by the conformational conversion of the normal cellular prion protein, PrPC, into the pathogenic isoform, PrPSc. Prion diseases are invariably fatal and despite ongoing research, no effective prophylactic or therapeutic avenues are currently available. Anthocyanins (ACNs) are unique flavonoid compounds and interest in their use as potential neuroprotective and/or therapeutic agents against NDs, has increased significantly in recent years. Therefore, we investigated the potential anti-oxidant and anti-prion effects of Oenin and Myrtillin, two of the most common anthocyanins, using the most accepted in the field overexpressing PrPScin vitro model and a cell free protein aggregation model. Our results, indicate both anthocyanins as strong anti-oxidant compounds, upregulating the expression of genes involved in the anti-oxidant response, and reducing the levels of Reactive Oxygen Species (ROS), produced due to pathogenic prion infection, through the activation of the Keap1-Nrf2 pathway. Importantly, they showcased remarkable anti-prion potential, as they not only caused the clearance of pathogenic PrPSc aggregates, but also completely inhibited the formation of PrPSc fibrils in the Cerebrospinal Fluid (CSF) of patients with Creutzfeldt-Jakob disease (CJD). Therefore, Oenin and Myrtillin possess pleiotropic effects, suggesting their potential use as promising preventive and/or therapeutic agents in prion diseases and possibly in the spectrum of neurodegenerative proteinopathies.

The In Vitro, Ex Vivo, and In Vivo Effect of Edible Oils: A Review on Cell Interactions.

Consumption of edible oils is a significant part of the dietary pattern in the developed and developing world. Marine and vegetable oils are assumed to be part of a healthy food pattern, especially if one takes into account their potential role in protecting against inflammation, cardiovascular disease, and metabolic syndrome due to the presence of polyunsaturated fatty acids and minor bioactive compounds. Exploring the potential effect of edible fats and oils on health and chronic diseases is an emerging field worldwide. This study reviews the current knowledge of the in vitro, ex vivo, and in vivo effect of edible oils in contact with various cell types and aims to demonstrate which nutritional and bioactive components of a variety of edible oils present biocompatibility, antimicrobial properties, antitumor activity, anti-angiogenic activity, and antioxidant activity. Through this review, a wide variety of cell interactions with edible oils and their potential to counteract oxidative stress in pathological conditions are presented as well. Moreover, the gaps in current knowledge are also highlighted, and future perspectives on edible oils and their health benefits and potential to counteract a wide variety of diseases through possible molecular mechanisms are also discussed.

Artemisinin Loaded Cerium-Doped Nanopowders Improved In Vitro the Biomineralization in Human Periodontal Ligament Cells.

BACKGROUND: A promising strategy to enhance bone regeneration is the use of bioactive materials doped with metallic ions with therapeutic effects and their combination with active substances and/or drugs. The aim of the present study was to investigate the osteogenic capacity of human periodontal ligament cells (hPDLCs) in culture with artemisinin (ART)-loaded Ce-doped calcium silicate nanopowders (NPs); Methods: Mesoporous silica, calcium-doped and calcium/cerium-doped silicate NPs were synthesized via a surfactant-assisted cooperative self-assembly process. Human periodontal ligament cells (hPDLCs) were isolated and tested for their osteogenic differentiation in the presence of ART-loaded and unloaded NPs through alkaline phosphatase (ALP) activity and Alizarine red S staining, while their antioxidant capacity was also evaluated; Results: ART promoted further the osteogenic differentiation of hPDLCs in the presence of Ce-doped NPs. Higher amounts of Ce in the ART-loaded NPs inversely affected the mineral deposition process by the hPDLCs. ART and Ce in the NPs have a synergistic role controlling the redox status and reducing ROS production from the hPDLCs; Conclusions: By monitoring the Ce amount and ART concentration, mesoporous NPs with optimum properties can be developed towards bone tissue regeneration demonstrating also potential application in periodontal tissue regeneration strategies.

Study of Biological Behavior and Antimicrobial Properties of Cerium Oxide Nanoparticles.

(1) Background: An element that has gained much attention in industrial and biomedical fields is Cerium (Ce). CeO2 nanoparticles have been proven to be promising regarding their different biomedical applications for the control of infection and inflammation. The aim of the present study was to investigate the biological properties and antimicrobial behavior of cerium oxide (CeO2) nanoparticles (NPs). (2) Methods: The investigation of the NPs' biocompatibility with human periodontal ligament cells (hPDLCs) was evaluated via the MTT assay. Measurement of alkaline phosphatase (ALP) levels and alizarine red staining (ARS) were used as markers in the investigation of CeO2 NPs' capacity to induce the osteogenic differentiation of hPDLCs. Induced inflammatory stress conditions were applied to hPDLCs with H2O2 to estimate the influence of CeO2 NPs on the viability of cells under these conditions, as well as to reveal any ROS scavenging properties. Total antioxidant capacity (TAC) of cell lysates with NPs was also investigated. Finally, the macro broth dilution method was the method of choice for checking the antibacterial capacity of CeO2 against the anaerobic pathogens Porphyromonas gingivalis and Prevotella intermedia. (3) Results: Cell viability assay indicated that hPDLCs increase their proliferation rate in a time-dependent manner in the presence of CeO2 NPs. ALP and ARS measurements showed that CeO2 NPs can promote the osteogenic differentiation of hPDLCs. In addition, the MTT assay and ROS determination demonstrated some interesting results concerning the viability of cells under oxidative stress conditions and, respectively, the capability of NPs to decrease free radical levels over the course of time. Antimicrobial toxicity was observed mainly against P. gingivalis. (4) Conclusions: CeO2 NPs could provide an excellent choice for use in clinical practices as they could prohibit bacterial proliferation and control inflammatory conditions.

Oil from Mullet Roe Byproducts: Effect of Oil Extraction Method on Human Erythrocytes and Platelets.

Background: The valorization of byproducts to obtain high nutritional value foods is of utmost importance for our planet where the population is booming. Among these products are oils rich in ω-3 fatty acids produced from fishery byproducts. Recently, mullet roe oil from roe byproducts was produced that was rich in the ω-3 fatty acids eicosatetraenoic acid (EPA) and docosahexaenoic acid (DHA). Oils are customarily characterized for their composition and degree of oxidation but little is known of their biological effects, especially the effect of the extraction method. Methods: The purpose of this study was to evaluate the effects of freshly extracted mullet roe oil from mullet roe byproducts and the effect of the extraction method on human red blood cells (hRBCs) and platelets. To this end, the hemocompatibility (cytotoxicity), oxidative effects, and erythrocyte membrane changes were examined after 1 and 24 h of incubation. Antiplatelet effects were also assessed in vitro. Results: The expeller press oil extraction method and alcalase-assisted extraction produced the most biocompatible oils, as shown by hemocompatibility measurements and the absence of erythrocyte membrane alterations. Solvent extracts and protease-assisted extraction oils resulted in the rupture of red blood cells at different examined dilutions, creating hemolysis. Conclusions: It seems that the proper functioning of oil-erythrocyte interactions cannot be explained solely by ROS. Further investigations combining chemical analysis with oil-cell interactions could be used as an input to design high nutritional value oils using green extraction technologies. All samples exhibited promising antiplatelet and antiblood clotting effects in vitro.

Composite PLGA-Nanobioceramic Coating on Moxifloxacin-Loaded Akermanite 3D Porous Scaffolds for Bone Tissue Regeneration.

Silica-based ceramics doped with calcium and magnesium have been proposed as suitable materials for scaffold fabrication. Akermanite (Ca2MgSi2O7) has attracted interest for bone regeneration due to its controllable biodegradation rate, improved mechanical properties, and high apatite-forming ability. Despite the profound advantages, ceramic scaffolds provide weak fracture resistance. The use of synthetic biopolymers such as poly(lactic-co-glycolic acid) (PLGA) as coating materials improves the mechanical performance of ceramic scaffolds and tailors their degradation rate. Moxifloxacin (MOX) is an antibiotic with antimicrobial activity against numerous aerobic and anaerobic bacteria. In this study, silica-based nanoparticles (NPs) enriched with calcium and magnesium, as well as copper and strontium ions that induce angiogenesis and osteogenesis, respectively, were incorporated into the PLGA coating. The aim was to produce composite akermanite/PLGA/NPs/MOX-loaded scaffolds through the foam replica technique combined with the sol-gel method to improve the overall effectiveness towards bone regeneration. The structural and physicochemical characterizations were evaluated. Their mechanical properties, apatite forming ability, degradation, pharmacokinetics, and hemocompatibility were also investigated. The addition of NPs improved the compressive strength, hemocompatibility, and in vitro degradation of the composite scaffolds, resulting in them keeping a 3D porous structure and a more prolonged release profile of MOX that makes them promising for bone regeneration applications.

The Role of Equilibrium between Free Radicals and Antioxidants in Depression and Bipolar Disorder.

Background: Increasing evidence suggests that the presence of oxidative stress and disorders of the antioxidant defense system are involved in a wide range of neuropsychiatric disorders, such as bipolar disorder, schizophrenia and major depression, but the exact mechanism remains unknown. This review focuses on a better appreciation of the contribution of oxidative stress to depression and bipolar disorder. Methods: This review was conducted by extracting information from other research and review studies, as well as other meta-analyses, using two search engines, PubMed and Google Scholar. Results: As far as depression is concerned, there is agreement among researchers on the association between oxidative stress and antioxidants. In bipolar disorder, however, most of them observe strong lipid peroxidation in patients, while regarding antioxidant levels, opinions are divided. Nevertheless, in recent years, it seems that on depression, there are mainly meta-analyses and reviews, rather than research studies, unlike on bipolar disorder. Conclusions: Undoubtedly, this review shows that there is an association among oxidative stress, free radicals and antioxidants in both mental disorders, but further research should be performed on the exact role of oxidative stress in the pathophysiology of these diseases.

The Clinical Utility of ABO and RHD Systems as Potential Indicators of Health Status, a Preliminary Study in Greek Population.

OBJECTIVE: The objective of this study is to further highlight the differences between different ABO blood groups and Rhesus types with health biomarkers. METHODS: In total 150 active healthy blood donors participated in our study comprising of 80 males from 19-61 years and 70 females aged from 21 to 64. Participants carrying blood group A were 55 individuals, blood group B 32, blood group O 51, and blood group AB 12, RHD+ 132, and RHD- 18. All the volunteer regular blood donors were selected recognizing them as a healthy population excluding drug and supplements intake. Their blood samples were analyzed just before blood donation for biochemical, hematological, and antioxidant markers. Statistical computations were performed using the SPSS tool, specifically, the one-way ANOVA test, Chi-square statistics, and logistic regression were used as statistical models. RESULTS: O blood donors presented better iron absorption and the worst lipid profile. Indeed, a significant trend of high atheromatic index values revealed an increased risk for hyperlipidemia, in contrast with blood group A presenting a better lipid profile with lower atheromatic index values. There was also a gender related association for blood group A compared with O that was further highlighted using binary logistic regression. CONCLUSION: In this study, a significant difference was observed among the ABO blood groups in several of the examined biochemical and hematological biomarkers. O blood group appeared different behavior in comparison to all the tested blood groups and furthermore the RHD-group presented a better lipid profile in comparison to the RHD+ group. In order to obtain a more comprehensive view of the correlation between the ABO blood group and biochemical markers, further studies are required.

Potential Role of Certain Biomarkers Such as Vitamin B12, ROS, Albumin, as Early Predictors for Prognosis of COVID-19 Outcomes.

COVID-19 disease is still a major global concern because of its morbidity and its mortality in severe disease. Certain biomarkers including Reactive Oxygen Species (ROS), vitamins, and trace elements are known to play a crucial role in the pathophysiology of the disease. The aim of our study was to evaluate how certain biomarkers, such as ROS, biochemical indicators, trace elements in serum blood of 139 COVID-19 hospitalized patients, and 60 non-COVID cases according to age and sex variations, can serve as the predictors for prognosis of COVID-19 outcome. An attempt of correlating these biomarkers with the severity of the disease as well as with each other is represented. All subjects were hospitalized from April 2021 until June 2021. A statistically significant increase of B12 levels (p = 0.0029) and ROS levels (p < 0.0001) as well as a decrease in albumin and Total Protein (T.P.) levels (p < 0.001) was observed especially in the early stage of the disease before CRP and ferritin elevation. Additionally, a statistically significant increase in ferritin (p = 0.007), B12 (p = 0.035, sALT p = 0.069, Glucose p = 0.012 and urea p = 0.096 and a decrease in Ca p = 0.005, T.P p = 0.052 albumin p = 0.046 between stage B (CRP values 6−30 mg/L) and C (CRP values 30−100 mg/L) was evident. Thus, this study concludes that clinicians could successfully employ biomarkers such as vitamin B12, ROS and albumin as possible prognosis tools for an early diagnosis. In addition, the total biochemical profile can assist in the understanding of the severity of COVID-19 disease, and could potentially lead to a better diet or early pharmaceutical treatment to prevent some of the more acute symptoms.

Impact of Drug Pressure versus Limited Access to Drug in Malaria Control: The Dilemma.

Malaria burden has severe impact on the world. Several arsenals, including the use of antimalarials, are in place to curb the malaria burden. However, the application of these antimalarials has two extremes, limited access to drug and drug pressure, which may have similar impact on malaria control, leading to treatment failure through divergent mechanisms. Limited access to drugs ensures that patients do not get the right doses of the antimalarials in order to have an effective plasma concentration to kill the malaria parasites, which leads to treatment failure and overall reduction in malaria control via increased transmission rate. On the other hand, drug pressure can lead to the selection of drug resistance phenotypes in a subpopulation of the malaria parasites as they mutate in order to adapt. This also leads to a reduction in malaria control. Addressing these extremes in antimalarial application can be essential in maintaining the relevance of the conventional antimalarials in winning the war against malaria.

Resistance to artemisinin in falciparum malaria parasites: A redox-mediated phenomenon.

Malaria remains a major public health disease due to its high yearly mortality and morbidity. Resistance to the gold standard drug, artemisinin, is worrisome and needs better understanding in order to be overcome. In this work, we sought to study whether redox processes are involved in artemisinin resistance. As artemisinin is known to act among others via production of reactive species, we first compared the production of reactive oxygen species and concomitant protein oxidation in artemisinin-sensitive and artemisinin-resistant parasites when treated with artemisinin. The results undoubtedly demonstrated, using different original methods, that the level of ROS, including superoxide production, and oxidized protein were lower in the resistant strain. Interestingly, the major in-between strain difference was reported at the earlier ring stages, which are the forms able to enter in a quiescence state according to the ART resistance phenomenon. Moreover, we demonstrated a better homeostasis regulation in relation with higher expression of antioxidants in the artemisinin-resistant parasites than their sensitive counterparts after artemisinin exposure, notably, superoxide dismutase and the glutathione (GSH) system. These findings enrich the body of knowledges about the multifaceted mechanism of artemisinin resistance and will help in the design and development of newer antimalarials strategies active against resistant parasites.

A Preliminary Study about the Role of Reactive Oxygen Species and Inflammatory Process after COVID-19 Vaccination and COVID-19 Disease.

During the last couple of critical years, worldwide, there have been more than 550 million confirmed cases of COVID-19, including more than 6 million deaths (reported by the WHO); with respect to these cases, several vaccines, mainly mRNA vaccines, seem to prevent and protect from SARS-CoV-2 infection. We hypothesize that oxidative stress is one of the key factors playing an important role in both the generation and development of various kinds of disease, as well as antibody generation, as many biological paths can generate reactive oxygen species (ROS), and cellular activities can be modulated when ROS/antioxidant balance is interrupted. A pilot study was conducted in two stages during the COVID-19 pandemic in 2021 involving 222 participants between the ages of 26 and 66 years. ROS levels were measured before an after vaccination in the blood samples of 20 individuals who were vaccinated with two doses of mRNA vaccine, and an increase in ROS levels was observed after the first dose, with no modifications observed until the day before the second vaccination dose. A statistically significant difference (p < 0.001) was observed between time points 3 and 4 (before and after second dose), when participants were vaccinated for the second time, and ROS levels decreased from 21,758 to 17,580 a.u. In the second stage, blood was collected from 28 participants 45 days after COVID-19 infection (Group A), from 131 participants 45 days after receiving two doses of mRNA vaccine against COVID-19 (Group B), and from 13 healthy individuals as a control group (Group C). Additionally, antibodies levels were measured in all groups to investigate a possible correlation with ROS levels. A strong negative correlation was found between free radicals and disease antibodies in Group A (r = −0.45, p = 0.001), especially in the male subgroup (r = −0.88, p = 0.001), as well as in the female subgroup (r = −0.24, p < 0.001). Furthermore, no significant correlation (only a negative trend) was found with antibodies derived from vaccination in Group B (r = −0.01), and a negative trend was observed in the female subgroup, whereas a positive trend was observed in the male subgroup.