Tick-Talk: Human Babesiosis

Background: Human babesiosis is a parasitic infection caused by species of the protozoan Babesia, most commonly B. microti. The organism invades the erythrocytes causing them to lyse. The infection is transmitted through the Ixodes tick, which is commonly found on white mice and white tailed deer. Outbreaks of this disease most commonly occur in the Northeastern region of the United States, specifically New England and Long Island, New York, during spring and summer months, due to the greater proximity of vectors to humans. Patients who are infected can have a range of symptoms from asymptomatic to severe manifestations, including hospitalizations and mortality. Methods: Information was gathered through the use of the PubMed search engine. The search terms: (a) human babesiosis, (b) prevalence, (c) prevention, and (d) manifestations were used. To narrow the results the article types were limited to clinical trials and reviews. Other limitations included: (a) full text, (b) publication dates from 2008-2018, and (c) human species. This search provided 102 results. Results: According to the Centers for Disease Control and Prevention, in 2014 the highest incidence of babesiosis was in the found in: (a) New Jersey (159), (b) Rhode Island (172), (c) Connecticut (205), (d) New York (437), and (e) Massachusetts (537). A total of 1,744 incidences reported in the United States in 2014. Between 2011 and 2014 it was reported that roughly 2,165 cases of babesiosis required hospitalization. The highest rates per state in 2014 were found in: (a) Rhode Island (16.3), (b) Massachusetts (8.0), (c) Connecticut (5.7), (d) Maine (3.2), (e) New Hampshire (3.2), (f) New York (2.4), and (g) New Jersey (1.8). Immunocompromised patients, such as those who are: (a) asplenic, (b) HIV-infected, or (c) fighting malignancy, are more likely to experience severe symptoms and death as a result of babesiosis. In a recent study, those with more than one immunosuppressive condition were more likely to experience a prolonged disease state and despite multiple rounds of therapy, 20% of those patients died. Conclusions & Recommendations: It is recommended that those who detect a tick bite seek medical attention to remove the tick, and undergo lab testing. Most patients who are asymptomatic do not require treatment. Ill patients are treated for 7-10 days with a combination of two antibiotics. The two options include atovaquone and azithromycin or clindamycin and quinine for severely ill patients. Supportive treatment such as antipyretics and vasopressors may also be helpful. Preventative measures can be taken to lower the risk of babesiosis infection such as: (a) avoiding areas of high grass and shrubbery, (b) frequently mowing the lawn, (c) wearing long clothing when spending time outdoors, (d) checking oneself, children, and pets after spending times outdoors, (e) avoiding going off trails in wooded areas, and (f) wearing long pants that are tucked into socks if planning on spending time in areas where ticks are present. Additionally, many of the areas plagued with high incidence of infection are taking action by educating the public on ways to prevent further infections

Curcumin, Polydatin and Quercetin Synergistic Activity Protects from High-Glucose-Induced Inflammation and Oxidative Stress

none10noChronic hyperglycemia, the diagnostic biomarker of Type 2 Diabetes Mellitus (T2DM), is a condition that fosters oxidative stress and proinflammatory signals, both involved in the promotion of cellular senescence. Senescent cells acquire a proinflammatory secretory phenotype, called SASP, exacerbating and perpetuating the detrimental effects of hyperglycemia. Bioactive compounds can exert antioxidant and anti-inflammatory properties. However, the synergistic anti-inflammatory and antioxidant effects of the most extensively investigated natural compounds have not been confirmed yet in senescent cells and in hyperglycemic conditions. Here, we exposed young and replicative senescent HUVEC (yHUVEC and sHUVEC) to a high-glucose (HG) condition (45 mM) and treated them with Polydatin (POL), Curcumin (CUR) and Quercetin (QRC), alone or in combination (MIX), to mirror the anti-inflammatory component OxiDefTM contained in the novel nutraceutical GlicefenTM (Mivell, Italy). In both yHUVEC and sHUVEC, the MIX significantly decreased the expression levels of inflammatory markers, such as MCP-1, IL-1β and IL-8, and ROS production. Importantly, in sHUVEC, a synergistic effect of the MIX was observed, suggesting its senomorphic activity. Moreover, the MIX was able to reduce the expression level of RAGE, a receptor involved in the activation of proinflammatory signaling. Overall, our data suggest that the consumption of nutraceuticals containing different natural compounds could be an adjuvant supplement to counteract proinflammatory and pro-oxidative signals induced by both hyperglycemic and senescence conditions.openMatacchione, Giulia; Valli, Debora; Silvestrini, Andrea; Giuliani, Angelica; Sabbatinelli, Jacopo; Giordani, Chiara; Coppari, Sofia; Rippo, Maria Rita; Albertini, Maria Cristina; Olivieri, FabiolaMatacchione, Giulia; Valli, Debora; Silvestrini, Andrea; Giuliani, Angelica; Sabbatinelli, Jacopo; Giordani, Chiara; Coppari, Sofia; Rippo, Maria Rita; Albertini, Maria Cristina; Olivieri, Fabiol

Circulating levels of AGEs and soluble RAGE isoforms are associated with all-cause mortality and development of cardiovascular complications in type 2 diabetes: a retrospective cohort study

none10noopenSabbatinelli, Jacopo; Castiglione, Stefania; Macrì, Federica; Giuliani, Angelica; Ramini, Deborah; Vinci, Maria Cristina; Tortato, Elena; Bonfigli, Anna Rita; Olivieri, Fabiola; Raucci, AngelaSabbatinelli, Jacopo; Castiglione, Stefania; Macrì, Federica; Giuliani, Angelica; Ramini, Deborah; Vinci, Maria Cristina; Tortato, Elena; Bonfigli, Anna Rita; Olivieri, Fabiola; Raucci, Angel

The Association between Single Nucleotide Polymorphisms, including miR-499a Genetic Variants, and Dyslipidemia in Subjects Treated with Pharmacological or Phytochemical Lipid-Lowering Agents

none12noDisorders of lipoprotein metabolism are among the major risk factors for cardiovascular disease (CVD) development. Single nucleotide polymorphisms (SNPs) have been associated with the individual variability in blood lipid profile and response to lipid-lowering treatments. Here, we genotyped 34 selected SNPs located in coding genes related to lipid metabolism, inflammation, coagulation, and a polymorphism in the MIR499 gene-a microRNA previously linked to CVD-to evaluate the association with lipid trait in subjects with moderate dyslipidemia not on lipid-lowering treatment (Treatment-naïve (TN) cohort, n = 125) and in patients treated with statins (STAT cohort, n = 302). We also explored the association between SNPs and the effect of a novel phytochemical lipid-lowering treatment in the TN cohort. We found that 6 SNPs (in the MIR499, TNFA, CETP, SOD2, and VEGFA genes) were associated with lipid traits in the TN cohort, while no association was found with the response to twelve-week phytochemical treatment. In the STAT cohort, nine SNPs (in the MIR499, CETP, CYP2C9, IL6, ABCC2, PON1, IL10, and VEGFA genes) were associated with lipid traits, three of which were in common with the TN cohort. Interestingly, in both cohorts, the presence of the rs3746444 MIR499 SNP was associated with a more favorable blood lipid profile. Our findings could add information to better understand the individual genetic variability in maintaining a low atherogenic lipid profile and the response to different lipid-lowering therapies.openGiuliani, Angelica; Montesanto, Alberto; Matacchione, Giulia; Graciotti, Laura; Ramini, Deborah; Protic, Olga; Galeazzi, Roberta; Antonicelli, Roberto; Tortato, Elena; Bonfigli, Anna Rita; Sabbatinelli, Jacopo; Olivieri, FabiolaGiuliani, Angelica; Montesanto, Alberto; Matacchione, Giulia; Graciotti, Laura; Ramini, Deborah; Protic, Olga; Galeazzi, Roberta; Antonicelli, Roberto; Tortato, Elena; Bonfigli, Anna Rita; Sabbatinelli, Jacopo; Olivieri, Fabiol

Mitochondrial (Dys) Function in Inflammaging: Do MitomiRs Influence the Energetic, Oxidative, and Inflammatory Status of Senescent Cells?

A relevant feature of aging is chronic low-grade inflammation, termed inflammaging, a key process promoting the development of all major age-related diseases. Senescent cells can acquire the senescence-associated (SA) secretory phenotype (SASP), characterized by the secretion of proinflammatory factors fuelling inflammaging. Cellular senescence is also accompanied by a deep reshaping of microRNA expression and by the modulation of mitochondria activity, both master regulators of the SASP. Here, we synthesize novel findings regarding the role of mitochondria in the SASP and in the inflammaging process and propose a network linking nuclear-encoded SA-miRNAs to mitochondrial gene regulation and function in aging cells. In this conceptual structure, SA-miRNAs can translocate to mitochondria (SA-mitomiRs) and may affect the energetic, oxidative, and inflammatory status of senescent cells. We discuss the potential role of several of SA-mitomiRs (i.e., let-7b, miR-1, miR-130a-3p, miR-133a, miR-146a-5p, miR-181c-5p, and miR-378-5p), using miR-146a as a proof-of-principle model. Finally, we propose a comprehensive, metabolic, and epigenetic view of the senescence process, in order to amplify the range of possible approaches to target inflammaging, with the ultimate goal of decelerating the aging rate, postponing or blunting the development of age-related diseases

Randomized, Double-Blind, Placebo-Controlled Trial to Test the Effects of a Nutraceutical Combination Monacolin K-Free on the Lipid and Inflammatory Profile of Subjects with Hypercholesterolemia

Background: Nutraceutical combinations (NCs) against hypercholesterolemia are increasing in the marketplace. However, the availability of NCs without monacolin K is scarce even though the statin-intolerant population needs it. Methods: This study is a parallel-group, randomized, placebo-controlled, double-blind trial. We evaluated the effects of the NC containing phytosterols, bergamot, olive fruits, and vitamin K2 on lipid profile and inflammatory biomarkers in 118 subjects (mean age ± SD, 57.9 ± 8.8 years; 49 men and 69 women) with hypercholesterolemia (mean total cholesterol ± SD, 227.4 ± 20.8 mg/dL) without clinical history of cardiovascular diseases. At baseline and 6 and 12 weeks of treatment, we evaluated lipid profile (total, LDL and HDL cholesterol, and triglycerides), safety (liver, kidney, and muscle parameters), and inflammatory biomarkers such as hs-CRP, leukocytes, interleukin-32, and interleukin-38 and inflammatory-microRNAs (miRs) miR-21, miR-126, and miR-146a. Results: Compared to the placebo, at 6 and 12 weeks, NC did not significantly reduce total cholesterol (p = 0.083), LDL cholesterol (p = 0.150), and triglycerides (p = 0.822). No changes were found in hs-CRP (p = 0.179), interleukin-32 (p = 0.587), interleukin-38 (p = 0.930), miR-21 (p = 0.275), miR-126 (p = 0.718), miR-146a (p = 0.206), myoglobin (p = 0.164), and creatine kinase (p = 0.376). Among the two reported, only one adverse event was probably related to the nutraceutical treatment. Conclusions: The evaluated nutraceutical combination did not change serum lipid profile and inflammatory parameters, at least not with the daily dose applied in the present study

Prognostic value of soluble ST2, high-sensitivity cardiac troponin, and NT-proBNP in type 2 diabetes: a 15-year retrospective study

Background: Patients with type 2 diabetes (T2DM) present an increased risk of cardiovascular (CV) disease and excess CV-related mortality. Beyond the established role of brain natriuretic peptide (BNP) and cardiac troponins (cTn), other non-cardiac-specific biomarkers are emerging as predictors of CV outcomes in T2DM. Methods: Serum levels of soluble suppression of tumorigenesis 2 (sST2), high-sensitivity (hs)-cTnI, and N-terminal (NT)-proBNP were assessed in 568 patients with T2DM and 115 healthy controls (CTR). Their association with all-cause mortality and the development of diabetic complications was tested in T2DM patients over a median follow-up of 16.8 years using Cox models and logistic regressions. Results: sST2 followed an increasing trend from CTR to uncomplicated T2DM patients (T2DM-NC) to patients with at least one complication (T2DM-C), while hs-cTnI was significantly higher in T2DM-C compared to CTR but not to T2DM-NC. A graded association was found between sST2 (HR 2.76 [95% CI 1.20-6.33] for ≥ 32.0 ng/mL and 2.00 [1.02-3.94] for 16.5-32.0 ng/mL compared to < 16.5 ng/mL, C-statistic = 0.729), NT-proBNP (HR 2.04 [1.90-4.55] for ≥ 337 ng/L and 1.48 [1.05-2.10] for 89-337 ng/L compared to < 89 ng/L, C-statistic = 0.741), and 15-year mortality in T2DM, whereas increased mortality was observed in patients with hs-cTnI ≥ 7.8 ng/L (HR 1.63 [1.01-2.62]). A 'cardiac score' based on the combination of sST2, hs-cTnI, and NT-proBNP was significantly associated with all-cause mortality (HR 1.35 [1.19-1.53], C-statistic = 0.739) and development of CV events. Conclusions: sST2, hs-cTnI, and NT-proBNP are associated with 15-year mortality and onset of CV events in T2DM. The long-term prognostic value of sST2 and its ability to track variables related to insulin resistance and associated metabolic disorders support its implementation into routine clinical practice

Attenuation of Listeria monocytogenes Virulence by Cannabis sativa L. Essential Oil

Anti-virulence strategies are being explored as a novel approach to combat pathogens. Such strategies include inhibition of surface adhesion, tissue invasion, toxin production, and/or interference with the gene regulation of other virulence traits. Listeria monocytogenes, the causative agent of listeriosis, is a facultative intracellular food pathogen characterized by a wide distribution in the environment. Its ability to persist within biofilms and to develop resistance to sanitizers is the cause of significant problems in food processing plants and of steep costs for the food industry. In humans, the treatment of listeriosis is hampered by the intracellular location of listeriae and the poor intracellular penetration of some antibiotics. Eleven L. monocytogenes isolates from patients who were diagnosed with invasive listeriosis in Italy in 2014–2016 were studied. This in vitro and in vivo study explored the antibacterial and anti-virulence properties of a steam-distilled essential oil of Cannabis sativa L., which is being intensively investigated for its high content in powerful bioactive phytochemicals. Susceptibility experiments demonstrated a moderate bactericidal activity of the essential oil (Minimum Bactericidal Concentration > 2048 μg/mL). Assessment of the effects of sublethal concentrations of the essential oil on L. monocytogenes virulence traits demonstrated a significant action on motility. Listeriae were non-motile after exposure to the essential oil. Light and scanning electron microscopy documented aggregates of listeriae with the flagella trapped inside the cluster. Real-time RT-PCR experiments showed downregulation of flagellar motility genes and of the regulatory gene prfA. The ability to form biofilm and to invade Caco-2 cells was also significantly reduced. Galleria mellonella larvae infected with L. monocytogenes grown in presence of sublethal concentrations of the essential oil showed much higher survival rates compared with controls, suggesting that the extract inhibited tissue invasion. Food contamination with L. monocytogenes is a major concern for the food industry, particularly for plants making ready-to-eat and processed food. The present work provides a baseline in the study of the anti-virulence properties of the C. sativa essential oil against L. monocytogenes. Further studies are needed to understand if it could be used as an alternative agent for the control of L. monocytogenes in food processing plants

Simple Detection of Unstained Live Senescent Cells with Imaging Flow Cytometry

Cellular senescence is a hallmark of aging and a promising target for therapeutic approaches. The identification of senescent cells requires multiple biomarkers and complex experimental procedures, resulting in increased variability and reduced sensitivity. Here, we propose a simple and broadly applicable imaging flow cytometry (IFC) method. This method is based on measuring autofluorescence and morphological parameters and on applying recent artificial intelligence (AI) and machine learning (ML) tools. We show that the results of this method are superior to those obtained measuring the classical senescence marker, senescence-associated beta-galactosidase (SA-β-Gal). We provide evidence that this method has the potential for diagnostic or prognostic applications as it was able to detect senescence in cardiac pericytes isolated from the hearts of patients affected by end-stage heart failure. We additionally demonstrate that it can be used to quantify senescence “in vivo” and can be used to evaluate the effects of senolytic compounds. We conclude that this method can be used as a simple and fast senescence assay independently of the origin of the cells and the procedure to induce senescence