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Colorectal cancer (CRC) continues to be a significant contributor to global morbidity and mortality. Emerging evidence indicates that disturbances in gut microbial composition, the formation of reactive oxygen species (ROS), and the resulting inflammation can lead to DNA damage, driving the pathogenesis and progression of CRC. Notably, bacterial metabolites can either protect against or contribute to oxidative stress by modulating the activity of antioxidant enzymes and influencing signaling pathways that govern ROS-induced inflammation. Additionally, microbiota byproducts, when supplemented through probiotics, can affect tumor microenvironments to enhance treatment efficacy and selectively mediate the ROS-induced destruction of CRC cells. This review aims to discuss the mechanisms by which taxonomical shifts in gut microbiota and related metabolites such as short-chain fatty acids, secondary bile acids, and trimethylamine-N-oxide influence ROS concentrations to safeguard or promote the onset of inflammation-mediated CRC. Additionally, we focus on the role of probiotic species in modulating ROS-mediated signaling pathways that influence both oxidative status and inflammation, such as Nrf2-Keap1, NF-κB, and NLRP3 to mitigate carcinogenesis. Overall, a deeper understanding of the role of gut microbiota on oxidative stress may aid in delaying or preventing the onset of CRC and offer new avenues for adjunct, CRC-specific therapeutic interventions such as cancer immunotherapy.
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Antioxidantes , Neoplasias Colorretais , Microbioma Gastrointestinal , Inflamação , Estresse Oxidativo , Probióticos , Humanos , Probióticos/uso terapêutico , Probióticos/farmacologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/microbiologia , Neoplasias Colorretais/etiologia , Antioxidantes/uso terapêutico , Antioxidantes/metabolismo , Inflamação/metabolismo , Animais , Espécies Reativas de Oxigênio/metabolismo , Transdução de SinaisRESUMO
Background Assessing micronutrient intake is important in identifying deficiencies that may contribute to insulin resistance, poor glycemic control, and increased risk of diabetes-related complications. The study's objectives were to evaluate micronutrient intake in prediabetes (PD) and type 2 diabetes (T2DM) patients compared to recommended dietary intakes (RDI) and to determine the associations between the micronutrient patterns and both anthropometric measurements and biomarkers of diabetes. Methods This cross-sectional study was conducted on 349 patients with T2DM and 252 patients with PD. Micronutrient intake was evaluated using a validated food frequency questionnaire. Micronutrient patterns were extracted from factor analysis using principal component analysis with varimax rotation. Participants in the highest tertile were considered to have the highest adherence to the corresponding micronutrient pattern. Results T2DM patients had a significantly lower intake of vitamin E (9.4 ± 0.2 vs. 10.1 ± 0.3 mg; p = 0.048), vitamin D (44.3 ± 1.1 vs. 48.9 ± 1.7 IU; p = 0.020), and thiamin (1.3 ± 0.1 vs. 1.4 ± 0.1 mg; p = 0.013) compared to PD patients. All patients had a significantly lower intake of vitamin A, vitamin D, folate, magnesium, and potassium and a significantly higher intake of vitamin B12 and copper compared to RDI. Three distinct micronutrient patterns were identified within each group. In the PD group, the Fe-Mn-Se pattern correlated significantly with waist circumference (WC) and fasting plasma glucose (FPG). The Vit.C-K-Folate pattern showed significant associations with body fat (BF). The Vit.B2-P-Vit.B12 pattern was significantly linked to WC, body mass index (BMI), BF, FPG, and serum insulin (SI). For the T2DM patients, the K-Folate-Mg pattern displayed an inverse and significant association with weight and WC. The Iron-Se-Vit.B3 pattern showed a significant association with low-density lipoprotein (LDL) cholesterol, triglycerides, and total cholesterol. The Vit.B2-P-Ca pattern was significantly associated with fasting plasma glucose (FPG). Conclusion This study demonstrated that T2DM patients had significantly lower vitamin E, vitamin D, and thiamin intake than PD patients. Both T2DM and PD patients had a significantly lower intake of vitamin A, vitamin D, folate, magnesium, and potassium compared to the RDI. Among the identified micronutrient patterns, only the K-Folate-Mg pattern exhibited a significant association with reduced body weight and WC.
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The coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 has been defined as the greatest global health and socioeconomic crisis of modern times. While most people recover after being infected with the virus, a significant proportion of them continue to experience health issues weeks, months and even years after acute infection with SARS-CoV-2. This persistence of clinical symptoms in infected individuals for at least three months after the onset of the disease or the emergence of new symptoms lasting more than two months, without any other explanation and alternative diagnosis have been named long COVID, long-haul COVID, post-COVID-19 conditions, chronic COVID, or post-acute sequelae of SARS-CoV-2 (PASC). Long COVID has been characterized as a constellation of symptoms and disorders that vary widely in their manifestations. Further, the mechanisms underlying long COVID are not fully understood, which hamper efficient treatment options. This review describes predictors and the most common symptoms related to long COVID's effects on the central and peripheral nervous system and other organs and tissues. Furthermore, the transcriptional markers, molecular signaling pathways and risk factors for long COVID, such as sex, age, pre-existing condition, hospitalization during acute phase of COVID-19, vaccination, and lifestyle are presented. Finally, recommendations for patient rehabilitation and disease management, as well as alternative therapeutical approaches to long COVID sequelae are discussed. Understanding the complexity of this disease, its symptoms across multiple organ systems and overlapping pathologies and its possible mechanisms are paramount in developing diagnostic tools and treatments.
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COVID-19 , Humanos , Síndrome de COVID-19 Pós-Aguda , SARS-CoV-2 , Gerenciamento Clínico , Progressão da DoençaRESUMO
The present study focused on the development of gel-based capsules from sodium alginate and the fresh juice from different berries: chokeberry, sea buckthorn, and blueberry. Obtained through the extrusion method, the macrocapsules were added into yogurt, a well-known and consumed dairy product. In order to establish the changes that can occur for the food product, the samples were tested over 7 and 15 days of storage in refrigeration conditions. According to the results, the antioxidant activity increased during storage and gels can represent a good option for bioactive substances' encapsulation. Sensorial analysis performed indicated that consumers are open to consuming yogurt berry capsules and, according to the results observed in the scientific literature, they no longer rejected the product due to the bitterness and sourness of sea buckthorn or aronia. Sea buckthorn capsules were brighter (L*) than chokeberry and blueberry capsules due to carotene content and dark colors. Minimal diameter variations and small standard deviations (SD = 0.25/0.33) suggest that extrusion methods and the Caviar box are good for gel capsule development. Yogurt luminosity varied with capsules; control had the highest, followed by sea buckthorn yogurt. Samples with chokeberry and blueberry (dark) capsules had lower luminosity. Over 8 and 15 days, luminosity slightly decreased, while a* and b* (hue and saturation) increased. Post-storage, the sample with chokeberry capsules showed a light purple color, indicating color transfer from capsules, with increased antioxidant activity. Differences between the samples and control were less pronounced in the sample with sea buckthorn capsules. Values for color differences between yogurt samples during the storage period revealed the most significant difference during the first storage period (day 1-8), with blueberries showing the lowest difference, indicating the stability of the blueberry capsules' wall during storage.
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As seen in earlier and present pandemics, monitoring pathogens in the environment can offer multiple insights on their spread, evolution, and even future outbreaks. The present paper assesses the opportunity to detect microbial pathogens and associated antibiotic resistance genes, in relation to specific pathogen sources, by using nanopore sequencing in municipal waters and wastewaters in Romania. The main results indicated that waters collecting effluents from a meat processing facility exhibit altered communities' diversity and abundance, with reduced values (101-108 and 0.86-0.91) of Chao1 and, respectively, Simpson diversity indices and Campylobacterales as main order, compared with other types of municipal waters where the same diversity index had much higher values of 172-214 and 0.97-0.98, and Burkholderiaceae and Pseudomonadaceae were the most abundant families. Moreover, the incidence and type of antibiotic resistance genes were significantly influenced by the proximity of antibiotic sources, with either tetracycline (up to 45% of total reads) or neomycin, streptomycin and tobramycin (up to 3.8% total reads) resistance incidence being shaped by the sampling site. As such, nanopore sequencing proves to be an easy-to-use, accessible molecular technique for environmental pathogen surveillance and associated antibiotic resistance genes.
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Modern biomedical sensing techniques have significantly increased in precision and accuracy due to new technologies that enable speed and that can be tailored to be highly specific for markers of a particular disease. Diagnosing early-stage conditions is paramount to treating serious diseases. Usually, in the early stages of the disease, the number of specific biomarkers is very low and sometimes difficult to detect using classical diagnostic methods. Among detection methods, biosensors are currently attracting significant interest in medicine, for advantages such as easy operation, speed, and portability, with additional benefits of low costs and repeated reliable results. Single-molecule sensors such as nanopores that can detect biomolecules at low concentrations have the potential to become clinically relevant. As such, several applications have been introduced in this field for the detection of blood markers, nucleic acids, or proteins. The use of nanopores has yet to reach maturity for standardization as diagnostic techniques, however, they promise enormous potential, as progress is made into stabilizing nanopore structures, enhancing chemistries, and improving data collection and bioinformatic analysis. This review offers a new perspective on current biomolecule sensing techniques, based on various types of nanopores, challenges, and approaches toward implementation in clinical settings.
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In the present work, the possibility of increasing the calcium carbonate (CaCO3) content in sheets of paper to optimize their properties was investigated. A new class of polymeric additives for papermaking is proposed as well as a method for their use in paper sheet containing the CaCO3 precipitated addition. Calcium carbonate precipitated (PCC) and fibers cellulose were adjusted with a cationic polyacrylamide flocculating agent (polydiallyldimethylammonium chloride (plyDADMAC) or cationic polyacrylamide (cPAM)). PCC was obtained in the laboratory by a double-exchange reaction between calcium chloride (CaCl2) and sodium carbonate (Na2CO3) suspension. After testing, the dosage of PCC was established at 35%. To improve the systems of additives studied, the materials obtained were characterized and their optical and mechanical properties were analysed. The PCC had a positive influence over all of the paper samples, but in the case of use of cPAM and polyDADMAC polymers the paper obtained had superior properties compared to the paper obtained without additives. Also, the samples obtained in the presence of cationic polyacrylamide exhibit superior properties to those obtained in the presence of polyDADMAC.
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With incidence of antimicrobial resistance rising globally, there is a continuous need for development of new antimicrobial molecules. Phenolic compounds having a versatile scaffold that allows for a broad range of chemical additions; they also exhibit potent antimicrobial activities which can be enhanced significantly through functionalization. Synthetic routes such as esterification, phosphorylation, hydroxylation or enzymatic conjugation may increase the antimicrobial activity of compounds and reduce minimal concentrations needed. With potent action mechanisms interfering with bacterial cell wall synthesis, DNA replication or enzyme production, phenolics can target multiple sites in bacteria, leading to a much higher sensitivity of cells towards these natural compounds. The current review summarizes some of the most important knowledge on functionalization of natural phenolic compounds and the effects on their antimicrobial activity.
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Anti-Infecciosos , Anti-Infecciosos/farmacologia , Fenóis/farmacologia , Extratos Vegetais , Antioxidantes , Antibacterianos/farmacologiaRESUMO
Long COVID, also known as post-acute sequelae of SARS-CoV-2 infection (PASC), has emerged as a significant health concern following the COVID-19 pandemic. Molecular mechanisms underlying the occurrence and progression of long COVID include viral persistence, immune dysregulation, endothelial dysfunction, and neurological involvement, and highlight the need for further research to develop targeted therapies for this condition. While a clearer picture of the clinical symptomatology is shaping, many molecular mechanisms are yet to be unraveled, given their complexity and high level of interaction with other metabolic pathways. This review summarizes some of the most important symptoms and associated molecular mechanisms that occur in long COVID, as well as the most relevant molecular techniques that can be used in understanding the viral pathogen, its affinity towards the host, and the possible outcomes of host-pathogen interaction.
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COVID-19 , Síndrome de COVID-19 Pós-Aguda , Humanos , Pandemias , SARS-CoV-2 , Progressão da DoençaRESUMO
The continuous development of drinking water networks is leading to the production of increasing amounts of waste water and sewage sludge. Secondary-treated sewage sludge is called biosolids and can be used as fertilizers in agriculture due to its rich nutrient content. The aim of this study was to evaluate the effects of biosolids mixed with an eroded soil on the morphology, physiology and synthesis of bioactive compounds in basil. The study was performed in pots under laboratory-controlled conditions. In total, four substrates were tested: S1 biosolids 100%, S2 biosolids 15% + eroded soil 85%, S3 eroded soil 100% and S4 control (commercial growing substrate). At the morphological level, a significant increase in plant height, number of branches, fresh biomass and dry biomass was found in the S2 variant. At the physiological level, photosynthesis and chlorophyll content did not vary significantly, but the quantum yield of PSII (ΦPSII) was significantly higher at S1 and S2. The oxidative status evaluated by determining the activity of SOD, POD and CAT enzymes was better in S2 and S3 compared to S3. Regarding the synthesis of bioactive compounds (rosmarinic acid, caffeic acid and gallic acid), it was stimulated in S1 and S2. In conclusion, biosolids application stimulated the stress response mechanisms in basil plants by increasing the quantum yield chlorophyll fluorescence and catalase activity, alleviating the negative effects of eroded soil.
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Ocimum basilicum , Biossólidos , Esgotos , Clorofila , Fenóis , SoloRESUMO
Fecal microbiota transplant (FMT) is a therapeutic method that aims to restore normal gut microbial composition in recipients. Currently, FMT is approved in the USA to treat recurrent and refractory Clostridioides difficile infection and has been shown to have great efficacy. As such, significant research has been directed toward understanding the potential role of FMT in other conditions associated with gut microbiota dysbiosis such as obesity, type 2 diabetes mellitus, metabolic syndrome, neuropsychiatric disorders, inflammatory bowel disease, irritable bowel syndrome, decompensated cirrhosis, cancers and graft-versus-host disease. This review examines current updates and efficacy of FMT in treating conditions other than Clostridioides difficile infection. Further, protocols for administration of FMT are also discussed including storage of fecal samples in stool banks, inclusion/exclusion criteria for donors, fecal sample preparation and methods of treatment administration. Overall, understanding the mechanisms by which FMT can manipulate gut microbiota to provide therapeutic benefit as well as identifying potential adverse effects is an important step in clarifying its long-term safety and efficacy in treating multiple conditions in the future.
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The benefits of using biopolymers for the development of films and coatings are well known. The enrichment of these material properties through various natural additions has led to their applicability in various fields. Essential oils, which are well-known for their beneficial properties, are widely used as encapsulating agents in films based on biopolymers. In this study, we developed biopolymer-based films and tested their properties following the addition of 7.5% and 15% (w/v) essential oils of lemon, orange, grapefruit, cinnamon, clove, chamomile, ginger, eucalyptus or mint. The samples were tested immediately after development and after one year of storage in order to examine possible long-term property changes. All films showed reductions in mass, thickness and microstructure, as well as mechanical properties. The most considerable variations in physical properties were observed in the 7.5% lemon oil sample and the 15% grapefruit oil sample, with the largest reductions in mass (23.13%), thickness (from 109.67 µm to 81.67 µm) and density (from 0.75 g/cm3 to 0.43 g/cm3). However, the microstructure of the sample was considerably improved. Although the addition of lemon essential oil prevented the reduction in mass during the storage period, it favored the degradation of the microstructure and the loss of elasticity (from 16.7% to 1.51% for the sample with 7.5% lemon EO and from 18.28% to 1.91% for the sample with 15% lemon EO). Although the addition of essential oils of mint and ginger resulted in films with a more homogeneous microstructure, the increase in concentration favored the appearance of pores and modifications of color parameters. With the exception of films with added orange, cinnamon and clove EOs, the antioxidant capacity of the films decreased during storage. The most obvious variations were identified in the samples with lemon, mint and clove EOs. The most unstable samples were those with added ginger (95.01%), lemon (92%) and mint (90.22%).
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The need to replace conventional, usually single-use, packaging materials, so important for the future of resources and of the environment, has propelled research towards the development of packaging-based on biopolymers, fully biodegradable and even edible. The current study furthers the research on development of such films and tests the modification of the properties of the previously developed biopolymeric material, by adding 10, respectively 20% w/v essential oils of lemon, grapefruit, orange, cinnamon, clove, mint, ginger, eucalypt, and chamomile. Films with a thickness between 53 and 102 µm were obtained, with a roughness ranging between 147 and 366 nm. Most films had a water activity index significantly below what is required for microorganism growth, as low as 0.27, while all essential oils induced microbial growth reduction or 100% inhibition. Tested for the evaluation of physical, optical, microbiological or solubility properties, all the films with the addition of essential oil in the composition showed improved properties compared to the control sample.
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Periodic removal of sediment from aquaculture ponds is practiced to maintain their productivity and animal welfare. The recovery of sediment as a plant fertilizer could alleviate the costs of sediment removal. The objective of this study was to test the effects of a dried sediment, extracted from an aquaculture pond used for common carp cultivation, on the growth and physiology of potted wheat grass and the quality of the juice obtained from wheat grass. The results showed that sediment application did not produce significant morphological changes, although the values for plant height (16.94-19.22 cm), leaf area (19.67-139.21 mm2), and biomass (3.39-4.26 g/plant) were higher in sediment-grown plants. However, at a physiological level, the effect was negative, decreasing photosynthesis (0.82-1.66 µmol CO2 m2s-1), fluorescence ΦPSII (0.737-0.782), and chlorophyll content (1.40-1.83 CCI). The juice yield was reduced in the sediment treatments (46-58 g/100 g), while the quality was improved by increasing the content of phenols (2.55-3.39 µg/mL gallic acid equivalent), flavonoids (1.41-1.85 µg/mL quercetin equivalent), and antioxidant activity (47.99-62.7% inhibition of; 2,2-diphenyl-1-picrylhydrazyl). The positive results obtained in this study can be attributed to the moderate nutrient content of the sediment and a negligible concentration of heavy metals.
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The ongoing COVID-19 pandemic follows an unpredictable evolution, driven by both host-related factors such as mobility, vaccination status, and comorbidities and by pathogen-related ones. The pathogenicity of its causative agent, SARS-CoV-2 virus, relates to the functions of the proteins synthesized intracellularly, as guided by viral RNA. These functions are constantly altered through mutations resulting in increased virulence, infectivity, and antibody-evasion abilities. Well-characterized mutations in the spike protein, such as D614G, N439K, Δ69-70, E484K, or N501Y, are currently defining specific variants; however, some less studied mutations outside the spike region, such as p. 3691 in NSP6, p. 9659 in ORF-10, 8782C > T in ORF-1ab, or 28144T > C in ORF-8, have been proposed for altering SARS-CoV-2 virulence and pathogenicity. Therefore, in this study, we focused on A105V mutation of SARS-CoV-2 ORF7a accessory protein, which has been associated with severe COVID-19 clinical manifestation. Molecular dynamics and computational structural analyses revealed that this mutation differentially alters ORF7a dynamics, suggesting a gain-of-function role that may explain its role in the severe form of COVID-19 disease.
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Wheat grass juice (WGJ) is an extract of young wheat plantlets (Triticum aetivum L.) used worldwide for its health related properties. In this study, the following feeds containing WGJ were tested on common carp (Cyprinus carpio L.): Control (C), WGJ1% (V1), WGJ2% (V2) and WGJ4% (V3) w/w. Fish with an average initial weight of 102 g/individual were grown in a recirculating aquaculture system. The results showed that WGJ had stimulatory effects on growth performance. Accordingly, final body weight increased by 11% at V1, 39% at V2 and 23% at V3, while other indices (feed conversion ratio, specific growth rate, relative growth rate, protein efficiency ratio, and condition factor) were unaffected. Body composition analyses revealed a significant decrease in fat content at V2 and a significant increase in collagen and ash at the same variant, while the protein content was unmodified. Regarding the blood profile, significant increases in the content of albumin, globulin, total protein, and calcium were recorded in the variants with WGJ. The positive results of WGJ on carp can be attributed to its biochemical composition, which is rich in chlorophyll (4.71 mg mL-1), total phenols (164 µg mL-1 gallic acid equivalents), and high antioxidant activity (67% inhibition of DPPH 2,2-diphenyl-1-picrylhydrazyl). The results suggest WGJ can be used as a promising feed additive for common carp.
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BACKGROUND: The United Kingdom reported the emergence of a new and highly transmissible SARS-CoV-2 variant (B.1.1.7) that rapidly spread to other countries. The impact of this new mutation-which occurs in the S protein-on infectivity, virulence, and current vaccine effectiveness is still under evaluation. OBJECTIVE: The aim of this study is to sequence SARS-CoV-2 samples of cases in Romania to detect the B.1.1.7 variant and compare these samples with sequences submitted to GISAID. METHODS: SARS-CoV-2 samples were sequenced and amino acid substitution analysis was performed using the CoV-GLUE platform. RESULTS: We have identified the first cases of the B.1.1.7 variant in samples collected from Romanian patients, of which one was traced to the region of the United Kingdom where the new variant was originally sequenced. Mutations in nonstructural protein 3 (Nsp3; N844S and D455N) and ORF3a (L15F) were also detected, indicating common ancestry with UK strains as well as remote connections with strains from Nagasaki, Japan. CONCLUSIONS: These results indicate, for the first time, the presence and characteristics of the new variant B.1.1.7 in Romania and underscore the need for increased genomic sequencing in patients with confirmed COVID-19.
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Romania officially declared its first Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) case on February 26, 2020. The first and largest coronavirus disease 2019 (COVID-19) outbreak in Romania was recorded in Suceava, North-East region of the country, and originated at the Suceava regional county hospital. Following sheltering-in-place measures, infection rates decreased, only to rise again after relaxation of measures. This study describes the spread of SARS-CoV-2 in Suceava and other parts of Romania and analyses the mutations and their association with clinical manifestation of the disease during the period of COVID-19 outbreak. Sixty-two samples were sequenced via high-throughput platform and screened for variants. For selected mutations, putative biological significance was assessed, and their effects on disease severity. Phylogenetic analysis was conducted on Romanian genomes (n = 112) and on sequences originating from Europe, United Kingdom, Africa, Asia, South, and North America (n = 876). The results indicated multiple introduction events for SARS-CoV-2 in Suceava, mainly from Italy, Spain, United Kingdom, and Russia although some sequences were also related to those from the Czechia, Belgium, and France. Most Suceava genomes contained mutations common to European lineages, such as A20268G, however, approximately 10% of samples were missing such mutations, indicating a possible different arrival route. While overall genome regions ORF1ab, S, and ORF7 were subject to most mutations, several recurring mutations such as A105V were identified, and these were mainly present in severe forms of the disease. Non-synonymous mutations, such as T987N (Thr987Asn in NSP3a domain), associated with changes in a protein responsible for decreasing viral tethering in human host were also present. Patients with diabetes and hypertension exhibited higher risk ratios (RR) of acquiring severe forms of the disease and these were mainly related to A105V mutation. This study identified the arrival routes of SARS-CoV-2 in Romania and revealed potential associations between the SARS-CoV-2 genomic organization circulating in the country and the clinical manifestation of COVID-19 disease.
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Recently, the implication of oxidative stress in behavioral-like disorders has received a lot of attention. Many studies were interested in searching for new natural compounds with protective effects on behavioral-like disorders by focusing on oxidative stress as the main causal factor. Here, we assess the potential effect of cell-free extracts from halophilic bacteria on memory, anxiety, and depression-related behaviors in mice, as well as on cognitive deficits, negative symptoms, and some oxidative stress biomarkers in methionine-induced mice models of schizophrenia. Firstly, crude extracts of bacteria isolated from the Dead Sea were screened for their effects on memory and anxiety- and depression-like behaviors through Y-maze, elevated plus maze, and forced swimming test, respectively, using two doses 60 mg/kg and 120 mg/kg. Then, 120 mg/kg of two bacterial crude extracts, from two strains designated SL22 and BM20 and identified as Bacillus stratosphericus and Pseudomonas zhaodongensis, respectively, with significant contents of phenolic and flavonoid-like compounds, were selected for the assessment of cognitive and negative symptom improvement, as well as for their effects on oxidative stress status in methionine-induced mice models of schizophrenia using six groups (controls, methionine, crude extracts solely, and combinations of crude extracts and methionine). Results showed that the administration of the crude extracts caused a significant increase in the spontaneous alternations in the Y-maze task, the time spent in open arms of the elevated plus maze, and a decrease in immobility time in the forced swimming test in comparison with the control group. Furthermore, the administration of bacterial extracts seemed to diminish disorders related to cognitive and negative symptoms of schizophrenia and to improve the oxidative state in the temporal lobes, in comparison with the methionine group. Our findings suggest substantial antioxidant and anti-neuropsychiatric effects of the crude extracts prepared from Pseudomonas zhaodongensis strain BM20 and Bacillus stratosphericus strain SL22 and that further studies are needed to purify and to determine the active fraction from the extracts.
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Combination of antibiotics with natural products is a promising strategy for potentiating antibiotic activity and overcoming antibiotic resistance. The purpose of the present study was to investigate whether morusin and kuwanon G, prenylated phenolics in Morus species, have the ability to enhance antibiotic activity and reverse antibiotic resistance in Staphylococcus aureus and Staphylococcus epidermidis. Commonly used antibiotics (oxacillin, erythromycin, gentamicin, ciprofloxacin, tetracycline, clindamycin) were selected for the combination studies. Checkerboard and time-kill assays were used to investigate potential bacteriostatic and bactericidal synergistic interactions, respectively between morusin or kuwanon G and antibiotics. According to both fractional inhibitory concentration index and response surface models, twenty combinations (14 morusin-antibiotic combinations, six kuwanon G-antibiotic combinations) displaying bacteriostatic synergy were identified, with 4-512-fold reduction in the minimum inhibitory concentration values of antibiotics in combination. Both morusin and kuwanon G reversed oxacillin resistance of methicillin-resistant Staphylococcus aureus. In addition, morusin reversed tetracycline resistance of Staphylococcus epidermidis. At half of the minimum inhibitory concentrations, combinations of morusin with oxacillin or gentamicin showed bactericidal synergy against methicillin-resistant Staphylococcus aureus. Fluorescence and differential interference contrast microscopy and scanning electron microscopy showed an increase in the membrane permeability and massive leakage of cellular content in methicillin-resistant Staphylococcus aureus exposed to morusin or kuwanon G. Overall, our findings strongly indicate that both prenylated compounds are good candidates for the development of novel antibacterial combination therapies.