ABSTRACT
BACKGROUND: Type 1 diabetes mellitus (T1DM) is characterized by immune and metabolic dysregulation. Apo1/Fas is implicated in maintaining homeostasis of the immune system. Cytokeratin-18 (cCK-18) is a predictive marker of liver disorders in T2DM. Intercellular adhesion molecule-1 (ICAM-1) is considered to increase susceptibility to diabetes mellitus. All three markers are associated with endothelial function, apoptosis and diabetes-related complications. The possible role of Apo1/Fas, cCK-18 and ICAM-1 was investigated in children and adolescents with T1DM. METHOD: Forty-nine (49) children and adolescents with T1DM and 49 controls were included in the study. Somatometric measurements were obtained and the Body Mass Index (BMI) of the participants was calculated. Biochemical parameters were measured by standard laboratory methods and Apo1/Fas, cCK-18 and ICAM-1 were measured using appropriate ELISA kits. The statistical analysis was performed using the IBM SPSS Statistics 23 program. RESULTS: Apo1/Fas (p = 0.001), cCK-18 (p < 0.001) and ICAM-1 (p < 0.001) were higher in patients with T1DM compared to the controls. Apo1Fas was negatively correlated with glucose (p = 0.042), uric acid (p = 0.026), creatinine (p = 0.022), total cholesterol (p = 0.023) and LDL (p = 0.005) in the controls. In children and adolescents with T1DM, Apo1/Fas was positively correlated with total cholesterol (p = 0.013) and LDL (p = 0.003). ICAM-1 was negatively correlated with creatinine (p = 0.019) in the controls, whereas in patients with T1DM it was negatively correlated with HbA1c (p = 0.05). CONCLUSIONS: Apo1/Fas, cCK-18 and ICAM-1 may be useful as serological markers for immune and metabolic dysregulation in children and adolescents with T1DM. Also, Apo1/Fas may have a protective role against metabolic complications in healthy children.
Subject(s)
Biomarkers , Diabetes Mellitus, Type 1 , Intercellular Adhesion Molecule-1 , Humans , Diabetes Mellitus, Type 1/blood , Intercellular Adhesion Molecule-1/blood , Child , Adolescent , Male , Female , Biomarkers/blood , Case-Control Studies , Keratin-18/blood , fas Receptor/blood , Apoptosis , Apolipoprotein A-I/bloodABSTRACT
Exogenous and endogenous advanced glycation end products (AGEs) contribute to the pathogenesis and progression of renal disease. This is a one-month controlled dietary counseling trial that restricts nutritional AGEs in patients with end-stage renal disease (ESRD) undergoing haemodialysis (n = 22 participants in the intervention and n = 20 participants in the control group). Haematological, biochemical markers, the soluble form of the receptor for AGEs (sRAGE), and carboxymethyl lysine (CML) were measured at baseline and at follow-up. Mononuclear cells were isolated and the protein expression of RAGE and the inflammatory marker COX-2 was measured using Western immunoblotting. The intervention group presented a lower increase in CML compared to the control group (12.39% median change in the intervention vs. 69.34% in the control group, p = 0.013), while RAGE (% mean change -56.54 in the intervention vs. 46.51 in the control group, p < 0.001) and COX-2 (% mean change -37.76 in the intervention vs. 0.27 in the control group, p < 0.001) were reduced compared to the control group. sRAGE was reduced in both groups. In addition, HbA1c (at two months), total cholesterol, and triglycerides were reduced in the intervention versus the control group. The adoption of healthy cooking methods deserves further research as a possible way of modulating inflammatory markers in patients with CKD.
Subject(s)
Glycation End Products, Advanced , Kidney Failure, Chronic , Lysine , Receptor for Advanced Glycation End Products , Renal Dialysis , Humans , Glycation End Products, Advanced/metabolism , Male , Female , Kidney Failure, Chronic/therapy , Kidney Failure, Chronic/metabolism , Kidney Failure, Chronic/diet therapy , Middle Aged , Lysine/analogs & derivatives , Lysine/metabolism , Receptor for Advanced Glycation End Products/metabolism , Aged , Inflammation/metabolism , Biomarkers , Adult , Cyclooxygenase 2/metabolismABSTRACT
Postprandial dysmetabolism is a common entity of type 2 diabetes mellitus (T2DM) and may act as a daily stressor of the already dysfunctional diabetic platelets. This study aims to investigate whether oleocanthal-rich olive oils (OO), incorporated into a carbohydrate-rich meal, can affect postprandial dysmetabolism and platelet aggregation. Oleocanthal is a cyclooxygenase inhibitor with putative antiplatelet properties. In this randomized, single-blinded, crossover study, ten T2DM patients consumed five isocaloric meals containing 120 g white bread combined with: (i) 39 g butter, (ii) 39 g butter and 400 mg ibuprofen, (iii) 40 mL OO (phenolic content < 10 mg/Kg), (iv) 40 mL OO with 250 mg/Kg oleocanthal and (v) 40 mL OO with 500 mg/Kg oleocanthal. Metabolic markers along with ex vivo ADP- and thrombin receptor-activating peptide (TRAP)-induced platelet aggregation were measured before and for 4 h after the meals. The glycemic and lipidemic response was similar between meals. However, a sustained (90-240 min) dose-dependent reduction in platelets' sensitivity to both ADP (50-100%) and TRAP (20-50%) was observed after the oleocanthal meals in comparison to OO or butter meals. The antiplatelet effect of the OO containing 500 mg/Kg oleocanthal was comparable to that of the ibuprofen meal. In conclusion, the consumption of meals containing oleocanthal-rich OO can reduce platelet activity during the postprandial period, irrespective of postprandial hyperglycemia and lipidemia.
Subject(s)
Aldehydes , Cyclopentane Monoterpenes , Diabetes Mellitus, Type 2 , Phenols , Humans , Diabetes Mellitus, Type 2/drug therapy , Olive Oil/pharmacology , Ibuprofen , Cross-Over Studies , Postprandial Period , ButterABSTRACT
Oxidative stress and apoptosis are involved in the pathogenesis of obesity-related diseases. This observational study investigates the antioxidant and apoptotic markers response to an oral glucose tolerance test (OGTT) in a population of overweight children and adolescents, with normal (NGT) or impaired glucose tolerance (IGT). Glucose, insulin, and C-peptide concentrations, as well as oxidative stress (SOD, GPx3) and apoptotic markers (Apo1fas, cck18), were determined at T = 0, 30, 60, 90, 120, and 180 min after glucose intake during OGTT. The lipid profile, thyroid function, insulin-like growth factor1, leptin, ghrelin, and adiponectin were also measured at baseline. The 45 participants, with a mean age of 12.15 (±2.3) years old, were divided into two subcategories: those with NGΤ (n = 31) and those with IGT (n = 14). The area under the curve (AUC) of glucose, insulin, and C-peptide was greater in children with IGT; however, only glucose differences were statistically significant. SOD and GPx3 levels were higher at all time points in the IGT children. Apo1fas and cck18 levels were higher in the NGT children at most time points, whereas Adiponectin was lower in the IGT group. Glucose increased during an OGTT accompanied by a simultaneous increase in antioxidant factors, which may reflect a compensatory mechanism against the impending increase in oxidative stress in children with IGT.
Subject(s)
Glucose Intolerance , Insulin Resistance , Humans , Adolescent , Child , Glucose Tolerance Test , Antioxidants , Blood Glucose , C-Peptide , Adiponectin , Insulin Resistance/physiology , Glucose , Insulin , Obesity , Weight Gain , Superoxide DismutaseABSTRACT
The prevalence and risk factors for Campylobacter spp. colonization of broiler flocks and broiler carcass contamination in Greek slaughterhouses were investigated. Over a 14-month period, a pool of 10 ceca and 5 neck skin samples from chicken carcasses were collected from each of 142 batches of broiler flocks slaughtered in 3 different slaughterhouses. Information on potential risk factors for Campylobacter infection in broilers was collected by an on-farm interview and linked according to the Campylobacter contamination status of broiler flocks and differences in farm characteristics and management practices identified from questionnaires. Campylobacter spp. was isolated from 73.94% and 70.42% of ceca (95% CI 65.92-80.94) and carcasses (95% CI 62.19-77.78), respectively. A significant correlation (p < 0.001) between the presence of Campylobacter spp. in broiler ceca and contamination of carcasses was found, suggesting the spread of the microorganism on the skin of carcasses during the slaughtering procedure. A multiple logistic regression showed the disinfection of the poultry house being conducted by unskilled personnel (odds ratio [OR] » = 3.983) as a significant risk factor (p < 0.05) and the use of straw litter as bedding material (OR » = 0.170) and closure of windows during the intervals of production cycles (OR » = 0.396) as significant protective factors (p < 0.05) for broiler flock contamination. These results are important and help further the understanding of the epidemiology of Campylobacter spp. derived from poultry in Greece.
Subject(s)
Campylobacter/isolation & purification , Chickens/microbiology , Food Contamination/analysis , Abattoirs , Animals , Food Microbiology , Greece , Meat/microbiology , Prevalence , Risk FactorsABSTRACT
Bacteria can form single- and multispecies biofilms exhibiting diverse features based upon the microbial composition of their community and microenvironment. The study of bacterial biofilm development has received great interest in the past 20 years and is motivated by the elegant complexity characteristic of these multicellular communities and their role in infectious diseases. Biofilms can thrive on virtually any surface and can be beneficial or detrimental based upon the community's interplay and the surface. Advances in the understanding of structural and functional variations and the roles that biofilms play in disease and host-pathogen interactions have been addressed through comprehensive literature searches. In this review article, a synopsis of the methodological landscape of biofilm analysis is provided, including an evaluation of the current trends in methodological research. We deem this worthwhile because a keyword-oriented bibliographical search reveals that less than 5% of the biofilm literature is devoted to methodology. In this report, we (i) summarize current methodologies for biofilm characterization, monitoring, and quantification; (ii) discuss advances in the discovery of effective imaging and sensing tools and modalities; (iii) provide an overview of tailored animal models that assess features of biofilm infections; and (iv) make recommendations defining the most appropriate methodological tools for clinical settings.
Subject(s)
Bacterial Physiological Phenomena , Biofilms , Animals , Humans , Microbiological Techniques/standards , Models, AnimalABSTRACT
PURPOSE: To investigate the effect of lifestyle habits in childhood Metabolic Syndrome (MTS). DESIGN AND METHODS: Descriptive correlation study with 480 participants (5-12â¯years old) using a specially designed questionnaire was conducted. Anthropometric and biochemical analyses were performed. RESULTS: Fifteen percent of children exhibited predisposition for MTS. Regarding sleep habits, logistic regression analysis (LRA) showed that hour of sleep -before 22:00- was associated with decreased waist circumference (WC%) (pâ¯=â¯.026). Midday siesta was negatively correlated with systolic (SBP) (pâ¯=â¯.001) and diastolic blood pressure (DBP) (pâ¯=â¯.046). In children without MTS, lack of sleep and night time sleep was positively correlated with DBP (pâ¯=â¯.044) and fasting blood glucose (FBG) (pâ¯=â¯.005). Regarding nutrition habits, fast food consumption was positively correlated with SBP (pâ¯=â¯.006) and meat consumption was positively correlated with both Body Mass Index% (BMI%) (pâ¯=â¯.038) and WC% (pâ¯=â¯.023). LRA showed that fruit (pâ¯=â¯.001) and legume (pâ¯=â¯.040) consumption was associated with decreased FBG; fish consumption with decreased Low Density Lipoprotein (LDL) cholesterol (pâ¯=â¯.031), vegetable (pâ¯=â¯.054) and cereal consumption (pâ¯=â¯.012) with decreased DBP. In children with MTS, fruits were associated with increased FBG (pâ¯=â¯.034). In children without MTS, meat consumption was associated with increased LDL (pâ¯=â¯.024), cereal with increased WC% (pâ¯=â¯.002) and olive products with increased High Density Lipoprotein (HDL) cholesterol and BMI% (pâ¯=â¯.037). CONCLUSIONS: The adoption of both balanced diet and sleep habits seemed to be crucial for the prevention of MTS. PRACTICE IMPLICATIONS: Clinical health nurses could develop and implement preventive intervention programs in order to avoid metabolic complications in adulthood.
Subject(s)
Child Welfare/statistics & numerical data , Health Promotion/organization & administration , Metabolic Syndrome/prevention & control , Nutritional Status , Pediatric Obesity/prevention & control , Attitude to Health , Body Mass Index , Child , Child, Preschool , Female , Food Preferences/psychology , Greece , Humans , Logistic Models , Male , Metabolic Syndrome/nursing , Pediatric Obesity/nursing , Risk FactorsABSTRACT
BACKGROUND: Anxiety combined with nervousness and apprehension consist a focal response to different life conditions. Lifestyle habits, anxiety and biochemical markers are in a constant interaction. AIM: To investigate the prevalence of anxiety in healthy adults and its possible association with biochemical factors-lipid profile, liver markers, thyroid hormones-and lifestyle habits. METHODS: Quantitative descriptive correlation study. A total of 100 healthy adults participated in the research. A specially designed questionnaire and Hamilton's scale were used. Anthropometric and biochemical analyses were performed. FINDINGS: Overall, 61% of the participants presented moderate to very serious anxiety. The average score on the Hamilton scale was 13.82 (±9.000), with men exhibiting less stress than women. For p ≤ 0.05: Stress was positively correlated with impaired thyroid and hepatic function. Hepatic function was affected by both sugar products and water melon, which were positively correlated with total bilirubin and AST/SGOT respectively. Tomato, peppers and legumes were negatively correlated with AST/SGOT. Deep fried food was positively correlated with GGT and triglycerides. Legumes and fish were negatively correlated with CPK. Regarding the lipid metabolism, it was found that food cooked with oil was positively associated with uric acid, but non-cooked olive oil was negatively correlated with the risk for CAD. Thyroid function was negatively correlated with non-homemade food and pasta consumption and positively correlated with consumption of whole grains and green tea. Participants with subclinical hypothyroidism seemed to consume less vitamin B12, folic acid and vegetables. CONCLUSION: No direct correlation between lifestyle habits and anxiety was found. Nevertheless, eating habits influenced biochemical markers-especially the thyroid hormones-which may be indirectly responsible for anxiety and related moods.
Subject(s)
Anxiety/physiopathology , Energy Metabolism/physiology , Feeding Behavior , Life Style , Nutritional Status , Adult , Anxiety/epidemiology , Anxiety/psychology , Body Mass Index , Eating/physiology , Female , Greece/epidemiology , Habits , Humans , Male , Middle Aged , Prevalence , Surveys and QuestionnairesABSTRACT
Telomerase is involved in the elongation of telomeres. It remains active in very few types of cell in mature organisms. One such cell type is the lymphocytes. In this study, we investigated the activity and expression of telomerase in lymphocytes from renal failure patients and compared it to that for normal controls. Inflammation status was determined at the same time. The enzyme activity was measured using PCR-ELISA with peripheral blood mononuclear cells (PBMCs) from three groups: 53 healthy individuals, 50 patients with chronic kidney disease (CKD) and 50 dialysis patients. In the same cell populations, the expression of the reverse transcriptase of the human telomerase gene (hTERT) was measured via real-time PCR. The inflammationstatus of these individuals was determined by calculating the interleukin 6 (IL-6), IL-10, C-reactive protein (CRP) and tumor necrosis factor alpha (TNF-a) serum concentrations via ELISA. The lowest levels of telomerase activity were detected in CKD, and this group had the highest IL-6 and CRP values and the lowest hTERT expression. The dialysis group showed significant differences in comparison to the normal subjects and to the CKD patients. Further studies are warranted in order to explore the way inflammation influences telomerase activity and hTERT expression.
Subject(s)
Inflammation , Leukocytes, Mononuclear/enzymology , Renal Insufficiency/enzymology , Telomerase/metabolism , Transcription, Genetic , Adult , Aged , Enzyme Assays , Female , Humans , Leukocytes, Mononuclear/immunology , Male , Middle Aged , Renal Insufficiency/immunology , Telomerase/geneticsABSTRACT
T-cell prolymphocytic leukemia (T-PLL) presents unique treatment challenges because of its rarity and aggressiveness. Allogeneic hematopoietic stem cell transplantation offers a potentially curative option, but its safety in patients with concurrent invasive fungal infections and solid malignancies remains uncertain. We present a case of a 68-year-old male with T-PLL who developed disseminated cryptococcal disease with prostate involvement and concurrent prostate cancer (PCa). Despite the challenges, successful control of the infection and radical prostatectomy enabled the patient to proceed safely to allogeneic transplantation. The case highlights the importance of vigilance for unusual infections, such as Cryptococcus, in immunocompromised patients presenting with lower urinary tract symptoms. Clinicians should consider the possibility of PCa in this population, particularly in the context of chronic leukemia. Concurrently, the potential association between fungal prostate infections and PCa warrants further investigation.
ABSTRACT
Malaria has become an emerging infection in Greece, which is the doorstep to Europe for thousands of immigrants. With increasing immigration, cases with evidence of domestic transmission (autochthonous) are being reported. In the present study, an isolate of Plasmodium vivax from an autochthonous clinical case was subjected to phylogenetic analysis of the genes encoding the merozoite surface protein 1 (MSP-1) and the circumsporozoite protein (CSP). In the MSP region, the strain was related with strains from Brazil, South Korea, Turkey and Thailand, whereas in the CSP region, with strains from Brazil, Colombia and New Guinea. The present study establishes for the first time in Greece the basis for the creation of a database comprising genotypic and phylogenetic characteristics of Plasmodium spp.
Subject(s)
Malaria, Vivax/diagnosis , Malaria, Vivax/parasitology , Merozoite Surface Protein 1/genetics , Plasmodium vivax/isolation & purification , Protozoan Proteins/genetics , Adult , Cluster Analysis , DNA, Protozoan/chemistry , DNA, Protozoan/genetics , Female , Greece , Humans , Molecular Sequence Data , Phylogeny , Plasmodium vivax/classification , Plasmodium vivax/genetics , Sequence Analysis, DNAABSTRACT
Surfaces have been implicated in the transmission of pathogens in hospitals. This study aimed to assess the effectiveness of an usnic-acid-containing self-decontaminating coating in reducing microbial surface contamination in tertiary-care hospitals. Samples were collected from surfaces 9 days before coating application, and 3, 10, and 21 days after its application (phases 1, 2, 3, and 4, respectively). Samples were tested for bacteria, fungi, and SARS-CoV2. In phase 1, 53/69 (76.8%) samples tested positive for bacteria, 9/69 (13.0%) for fungi, and 10/139 (7.2%) for SARS-CoV-2. In phase 2, 4/69 (5.8%) samples tested positive for bacteria, while 69 and 139 samples were negative for fungi and SARS-CoV-2, respectively. In phase 3, 3/69 (4.3%) samples were positive for bacteria, 1/139 (0.7%) samples tested positive for SARS-CoV-2, while 69 samples were negative for fungi. In phase 4, 1/69 (1.4%) tested positive for bacteria, while no fungus or SARS-CoV-2 were detected. After the coating was applied, the bacterial load was reduced by 87% in phase 2 (RR = 0.132; 95% CI: 0.108-0.162); 99% in phase 3 (RR = 0.006; 95% CI: 0.003-0.015); and 100% in phase 4 (RR = 0.001; 95% CI: 0.000-0.009). These data indicate that the usnic-acid-containing coating was effective in eliminating bacterial, fungal, and SARS-CoV-2 contamination on surfaces in hospitals.Our findings support the benefit ofan usnic-acid-containing coating in reducing the microbial load on healthcare surfaces.
Subject(s)
COVID-19 , SARS-CoV-2 , Humans , COVID-19/epidemiology , COVID-19/prevention & control , RNA, Viral , Tertiary Care CentersABSTRACT
Background: Chronic media with effusion (COME) and recurrent acute otitis media (RAOM) are closely related clinical entities that affect childhood. The aims of the study were to investigate the microbiological profile of otitis-prone children in the post-PCV7 era and, to examine the biofilm-forming ability in association with clinical history and outcome during a two-year post-operative follow-up. Methods: In this prospective study, pathogens from patients with COME and RAOM were isolated and studied in vitro for their biofilm-forming ability. The minimum inhibitory concentrations (MIC) of both the planktonic and the sessile forms were compared. The outcome of the therapeutic method used in each case and patient history were correlated with the pathogens and their ability to form biofilms. Results: Haemophilus influenzae was the leading pathogen (35% in COME and 40% in RAOM), and Streptococcus pneumoniae ranked second (12% in COME and 24% in RAOM). Polymicrobial infections were identified in 5% of COME and 19% of RAOM cases. Of the isolated otopathogens, 94% were positive for biofilm formation. Conclusions: This is the first Greek research studying biofilm formation in complex otitis media-prone children population in the post-PCV7 era. High rates of polymicrobial infections, along with treatment failure in biofilms, may explain the lack of antimicrobial efficacy in otitis-prone children.
ABSTRACT
(1) Background: Surfaces have been implicated in the transmission of infections. We aimed to assess how effective an usnic-acid-containing self-decontaminating coating was on the surfaces of the Athens underground metro. (2) Methods: Two samples were collected from each of 60 surfaces of a station and a wagon before the application of the coating and 9 and 20 days after, and they were tested for bacteria, fungi, and SARS-CoV-2 using conventional microbiological and molecular methods. Bacteria and fungi growth were expressed in colony forming units (CFUs)/102cm2. (3) Results: Before the application of the coating, 50% of the samples tested positive for the targeted microbes: 91.7% for bacteria, 18.3% for fungi, and 8.3% for SARS-CoV-2. After nine days, 3.3% of the samples tested positive for bacteria and 6.6% after 20 days. The average amount of bacteria before the coating was applied was 8.5 CFU/102cm2 compared to 0 and 0 CFU/102cm2 after application (100% and 95% reduction); all samples collected after the application were negative for SARS-CoV-2 and fungi (100% reduction). (4) Conclusion: An usnic-acid-containing self-decontaminating coating was highly effective in eliminating bacterial, fungal, and SARS-CoV-2 contamination of surfaces in the underground metro.
ABSTRACT
INTRODUCTION: Thyroxine is essential for nervous system development. Subclinical hypothyroidism (SCH), also known as mild thyroid failure, is associated with impaired cognitive function in children and mood disorders in adults. Serotonin is also involved in brain development as well as in mood and behavior modulation. The possible interaction between thyroid function tests, serum serotonin concentrations, and emotional intelligence (EI) was studied. METHODS: A total of 224 schoolchildren from the Peloponnese, Greece, aged 11-19, were included in the study, of whom 26.3% had SCH. Emotional quotients (EQ), such as well-being, self-control, emotionality, and sociability, were assessed using the TEIQue-ASF questionnaire, and TSH, fT4, and serum serotonin concentrations were also evaluated. RESULTS: Children and adolescents with SCH had a lower EQ total score (p < 0.001), EQ well-being score (p = 0.025), EQ self-control score (p = 0.029), EQ emotionality score (p = 0.029), and EQ sociability score (p = 0.010) and lower serum serotonin concentrations (p < 0.001). CONCLUSIONS: Children and adolescents with SCH exhibited lower EI scores and lower serum serotonin concentrations when compared with age-matched healthy controls.
Subject(s)
Emotional Intelligence , Hypothyroidism , Serotonin , Thyrotropin , Adolescent , Child , Humans , Serotonin/blood , Thyrotropin/blood , Thyroxine , Young AdultABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel virus that belongs to the Coronoviridae family, emerged in December 2019, causing the COVID-19 pandemic in March 2020. Unlike previous SARS and Middle East respiratory syndrome (MERS) outbreaks, this virus has a higher transmissibility rate, albeit a lower case fatality rate, which results in accumulation of a significant number of mutations and a faster evolution rate. Genomic studies on the mutation rate of the virus, as well as the identification of mutations that prevail and their impact on disease severity, are of great importance for pandemic surveillance and vaccine and drug development. Here, we aim to identify mutations on the SARS-CoV-2 viral genome and their effect on the proteins they are located in, in Greek patients infected in the first wave of the pandemic. To this end, we perform SARS-CoV-2 amplicon-based NGS sequencing on nasopharyngeal swab samples from Greek patients and bioinformatic analysis of the results. Although SARS-CoV-2 is considered genetically stable, we discover a variety of mutations on the viral genome. In detail, 18 mutations are detected in total on 10 SARS-CoV-2 isolates. The mutations are located on ORF1ab, S protein, M protein, ORF3a and ORF7a. Sixteen are also detected in patients from other regions around the world, and two are identified for the first time in the present study. Most of them result in amino acid substitutions. These substitutions are analyzed using computational tools, and the results indicate minor or major impact on the proteins' structural stability, which could probably affect viral transmissibility and pathogenesis. The correlation of these variations with the viral load levels is examined, and their implication for disease severity and the biology of the virus are discussed.
ABSTRACT
The SARS-CoV-2 infection was previously associated with the expression of the dopamine biosynthetic enzyme L-Dopa decarboxylase (DDC). Specifically, a negative correlation was detected between DDC mRNA and SARS-CoV-2 RNA levels in in vitro infected epithelial cells and the nasopharyngeal tissue of COVID-19 patients with mild/no symptoms. However, DDC, among other genes related to both DDC expression and SARS-CoV-2-infection (ACE2, dACE2, EPO), was upregulated in these patients, possibly attributed to an orchestrated host antiviral response. Herein, by comparing DDC expression in the nasopharyngeal swab samples of severe/critical to mild COVID-19 cases, we showed a 20 mean-fold reduction, highlighting the importance of the expression of this gene as a potential marker of COVID-19 severity. Moreover, we identified an association of SARS-CoV-2 infection with the expression of key catecholamine biosynthesis/metabolism-related genes, in whole blood samples from hospitalized patients and in cultured cells. Specifically, viral infection downregulated the biosynthetic part of the dopamine pathway (reduction in DDC expression up to 7.5 mean-fold), while enhanced the catabolizing part (increase in monoamine oxidases A and B expression up to 15 and 10 mean-fold, respectively) in vivo, irrespectively of the presence of comorbidities. In accordance, dopamine levels in the sera of severe cases were reduced (up to 3.8 mean-fold). Additionally, a moderate positive correlation between DDC and MAOA mRNA levels (r = 0.527, p < 00001) in the blood was identified upon SARS-CoV-2-infection. These observations were consistent to the gene expression data from SARS-CoV-2-infected Vero E6 and A549 epithelial cells. Furthermore, L-Dopa or dopamine treatment of infected cells attenuated the virus-derived cytopathic effect by 55% and 59%, respectively. The SARS-CoV-2 mediated suppression of dopamine biosynthesis in cell culture was, at least in part, attributed to hypoxia-like conditions triggered by viral infection. These findings suggest that L-Dopa/dopamine intake may have a preventive or therapeutic value for COVID-19 patients.
Subject(s)
COVID-19 , Humans , SARS-CoV-2/metabolism , Catecholamines , Dopamine , Levodopa/metabolism , RNA, Viral/metabolism , Biosynthetic Pathways , RNA, Messenger/metabolismABSTRACT
Silicon photonic probes based on broad-band Mach-Zehnder interferometry are explored for the first time as directly immersible immunosensors alleviating the need for microfluidics and pumps. Each probe includes two U-shaped waveguides allowing light in- and out-coupling from the same chip side through a bifurcated fiber and a mechanical coupler. At the opposite chip side, two Mach-Zehnder interferometers (MZI) are located enabling real-time monitoring of binding reactions by immersion of this chip side into a sample. The sensing arm windows of the two MZIs have different length resulting in two distinct peaks in the Fourier domain, the phase shift of which can be monitored independently through Fast Fourier Transform of the output spectrum. The photonic probes analytical potential was demonstrated through detection of antibodies against SARS-CoV-2 in human serum samples. For this, one MZI was functionalized with the Receptor Binding Domain (RBD) of SARS-CoV-2 Spike 1 protein, and the other with bovine serum albumin to serve as reference. The biofunctionalized probes were immersed for 10 min in human serum sample and then for 5 min in goat anti-human IgG Fc specific antibody solution. Using a humanized rat antibody against SARS-CoV-2 RBD, a detection limit of 20 ng/mL was determined. Analysis of human serum samples indicated that the proposed sensor discriminated completely non-infected/non-vaccinated from vaccinated individuals, and the antibodies levels determined correlated well with those determined in the same samples by ELISA. These results demonstrated the potential of the proposed sensor to serve as an efficient tool for expeditious point-of-care testing.
Subject(s)
Biosensing Techniques , COVID-19 , Animals , Antibodies , Antibodies, Viral , Biosensing Techniques/methods , COVID-19/diagnosis , COVID-19 Testing , Humans , Immunoassay , Rats , SARS-CoV-2 , Silicon/chemistryABSTRACT
INTRODUCTION/OBJECTIVES: Periodontitis comprises of a wide range of inflammatory conditions of the gums leading to soft tissue damage and attachment loss. The initiation of periodontitis constitutes a rather complex disease pathogenesis which is based on pathogenic shifts of the oral microbiota combined with the host-microbiome interactions. The severity of the periodontitis is multifactorial depending on genetic, environmental, as well as host immunity factors. DATA AND SOURCES: To make an inclusive analysis on the periodontitis therapeutics, reading of the recent relevant literature was carried out using the MEDLINE/PubMed database, Google Scholar and the NIH public online database for clinical trials (http://www.clinicaltrials.gov). CONCLUSIONS: Tackling the inflammation associated periodontal defects can be succeeded with conventional therapy or resective and regenerative treatment. To date, the mechanical removal of the supragingival and subgingival biofilm is considered the "gold standard" of periodontal therapy in combination with the use of antibacterial compounds. The antimicrobial resistance phenomenon tends to turn all the currently applied antibacterials into "endangered species". Ongoing efforts through the conduct of clinical trials should be focused on understanding the advantages of modern approaches in comparison to traditional therapies.
ABSTRACT
AIM: Oleocanthal and oleacein (OC/OL) have important in vitro and in vivo antitumor properties; however, there is no data about their anticancer activity in humans. The aim of this pilot study was to test if patients at early stage of chronic lymphocytic leukemia (CLL) could adhere to and tolerate an intervention with high OC/OL extra virgin olive oil (EVOO) and if this intervention could lead to any changes in markers related to the disease. METHODS: A pilot dietary intervention (DI) was made in patients with CLL in Rai stages 0-II who did not follow any treatment (NCT04215367). In the first intervention (DI1), 20 CLL patients were included in a blind randomized study and were separated into two groups. One group (A) of 10 patients consumed 40 ml/day of high OC/OL-EVOO (416 mg/Kg OC and 284 mg/kg OL) for 3 months. A second group (B) of 10 patients consumed 40 ml/day of low OC/OL (82 mg/kg OC and 33 mg/kg OL) for 3 months. After a washout period of 9-12 months, a second intervention (DI2) only with High OC/OL-EVOO for 6 months was performed with 22 randomly selected patients (16 from the DI1 (8 from each group) and 6 new). Hematological, biochemical, and apoptotic markers were analyzed in the serum of the patients. In addition, cellular proliferation and apoptosis markers were studied in isolated proteins from peripheral blood mononuclear cells. RESULTS: The results of the DI1 showed beneficial effects on hematological and apoptotic markers only with High OC/OL-EVOO. During the DI2, a decrease in the white blood cell and lymphocyte count was observed (p ≤0.05), comparing 3 months before the intervention and 6 months after it. After 3 and 6 months of DI2, an increase (p ≤0.05) was observed in the apoptotic markers ccK18 and Apo1-Fas, and also in the cell cycle negative regulator p21, and also a decrease in the antiapoptotic protein Survivin, and in the cellular proliferation marker Cyclin D. CONCLUSIONS: This is the first clinical trial with High OC/OL-EVOO that indicates that it could be a promising dietary feature for the improvement of CLL inducing the apoptosis of their cancer cells and improving the metabolism of the patients. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT04215367, identifier: NCT04215367.