Stephanoascus ciferrii Complex: The Current State of Infections and Drug Resistance in Humans.

In recent years, the incidence of fungal infections in humans has increased dramatically, accompanied by an expansion in the number of species implicated as etiological agents, especially environmental fungi never involved before in human infection. Among fungal pathogens, Candida species are the most common opportunistic fungi that can cause local and systemic infections, especially in immunocompromised individuals. Candida albicans (C. albicans) is the most common causative agent of mucosal and healthcare-associated systemic infections. However, during recent decades, there has been a worrying increase in the number of emerging multi-drug-resistant non-albicans Candida (NAC) species, i.e., C. glabrata, C. parapsilosis, C. tropicalis, C. krusei, C. auris, and C. ciferrii. In particular, Candida ciferrii, also known as Stephanoascus ciferrii or Trichomonascus ciferrii, is a heterothallic ascomycete yeast-like fungus that has received attention in recent decades as a cause of local and systemic fungal diseases. Today, the new definition of the S. ciferrii complex, which consists of S. ciferrii, Candida allociferrii, and Candida mucifera, was proposed after sequencing the 18S rRNA gene. Currently, the S. ciferrii complex is mostly associated with non-severe ear and eye infections, although a few cases of severe candidemia have been reported in immunocompromised individuals. Low susceptibility to currently available antifungal drugs is a rising concern, especially in NAC species. In this regard, a high rate of resistance to azoles and more recently also to echinocandins has emerged in the S. ciferrii complex. This review focuses on epidemiological, biological, and clinical aspects of the S. ciferrii complex, including its pathogenicity and drug resistance.

Closing the Gap in Proteomic Identification of Histoplasma capsulatum: A Case Report and Review of Literature.

Histoplasmosis is a globally distributed systemic infection caused by the dimorphic fungus Histoplasma capsulatum (H. capsulatum). This fungus can cause a wide spectrum of clinical manifestations, and the diagnosis of progressive disseminated histoplasmosis is often a challenge for clinicians. Although microscopy and culture remain the gold standard diagnostic tests for Histoplasma identification, matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS) has emerged as a method of microbial identification suitable for the confirmation of dimorphic fungi. However, to our knowledge, there are no entries for H. capsulatum spectra in most commercial databases. In this review, we describe the case of disseminated histoplasmosis in a patient living with HIV admitted to our university hospital that we failed to identify by the MALDI-TOF method due to the limited reference spectrum of the instrument database. Furthermore, we highlight the utility of molecular approaches, such as conventional polymerase chain reaction (PCR) and DNA sequencing, as alternative confirmatory tests to MALDI-TOF technology for identifying H. capsulatum from positive cultures. An overview of current evidence and limitations of MALDI-TOF-based characterization of H. capsulatum is also presented.

Bacterial Contamination of Healthcare Students' Mobile Phones: Impact of Specific Absorption Rate (SAR), Users' Demographics and Device Characteristics on Bacterial Load.

We quantitatively and qualitatively evaluated the bacterial contamination of mobile phones (MPs) in relation to users' demographics, habits, and device characteristics by administering questionnaires to 83 healthcare university students and sampling their MPs by following a cross-sectional design. The heterotrophic plate count (HPC) at 22 °C (HPC 22 °C) and 37 °C (HPC 37 °C), Enterococci, Gram-negative bacteria, and Staphylococci were evaluated. Higher bacterial loads were detected for HPC 37 °C and Staphylococci (416 and 442 CFU/dm2, respectively), followed by HPC 22 °C, Enterococci, and Gram-negative bacteria; the vast majority of samples were positive for HPC 37 °C, HPC 22 °C, and Staphylococci (98%), while Enterococci (66%) and Gram-negative bacteria (17%) were detected less frequently. A statistically significant positive correlation (r = 0.262, p < 0.02) was found between the European head specific absorption rate (SAR) and both HPC 37 °C and Staphylococci; Enterococci showed a strong, significant correlation with HPC 37 °C, HPC 22 °C, and Gram-negative bacteria (r = 0.633, 0.684, 0.884) and a moderate significant correlation with Staphylococci (r = 0.390). Significant differences were found between HPC 22 °C and the type of internship attendance, with higher loads for Medicine. Students with a daily internship attendance had higher HPC 22 °C levels than those attending <6 days/week. Our study showed that bacteria can survive on surfaces for long periods, depending on the user's habits and the device's characteristics.

Thymosin α1 interacts with Galectin-1 modulating the ß-galactosides affinity and inducing alteration in the biological activity.

The study of mechanism of action of Thymosin alpha 1 (Tα1) and the basis of the pleiotropic effect in health and disease, is one of the main focus of our ongoing research. Tα1 is a thymic peptide that demonstrates a peculiar ability to restore homeostasis in different physiological and pathological conditions (i.e., infections, cancer, immunodeficiency, vaccination, and aging) acting as multitasking protein depending on the host state of inflammation or immune dysfunction. However, few are the information about mechanisms of action mediated by specific Tα1-target protein interaction that could explain its pleiotropic effect. We investigated the interaction of Tα1 with Galectin-1 (Gal-1), a protein belonging to an oligosaccharide binding protein family involved in a variety of biological and pathological processes, including immunoregulation, infections, cancer progression and aggressiveness. Using molecular and cellular methodological approaches, we demonstrated the interaction between these two proteins. Tα1 specifically inhibited the hemagglutination activity of Gal-1, the Gal-1 dependent in vitro formation of endothelial cell tubular structures, and the migration of cancer cells in wound healing assay. Physico-chemical methods revealed the details of the molecular interaction of Tα1 with Gal-1. Hence, the study allowed the identification of the not known until now specific interaction between Tα1 and Gal-1, and unraveled a novel mechanism of action of Tα1 that could support understanding of its pleiotropic activity.

Microbiology and Clinical Outcome of Hospital-Acquired Respiratory Infections in an Italian Teaching Hospital: A Retrospective Study.

The burden, microbial etiology and clinical impact of hospital-acquired respiratory infections (HARIs) were determined at an Italian teaching hospital over a 12-month period. For this purpose, overall ordinary hospitalizations ≥ 2 days of subjects over 18 years old with discharge from 1 January 2018 to 31 December 2018 were examined by cross-referencing demographic and clinical data from hospital discharge forms with microbiological data from the computer system of the Microbiology Unit. We identified 329 individuals with HARIs (96 females and 233 males; median age 70 years, range 18−93), who represented » of the total hospital-acquired infections (HAIs) in the period. The inpatient setting was medical and surgical in similar proportions (169 vs. 160, respectively) and the mean hospital stay was 38.9 ± 33.6 days. One hundred and forty patients (42.6% of the total sample) were suffering from one or more chronic diseases. A total of 581 microorganisms (82 antibiotic-resistant and 499 non-resistant) were detected in HARI patients. The most common isolated species were Staphylococcus aureus (16.7%), Klebsiella pneumoniae (13.3%), Pseudomonas spp. (12.6%) and Acinetobacter baumannii (10.5%), followed by Enterobacter spp. (5.3%), Escherichia coli (5.2%) and Enterococcus spp. (4.8%). One hundred and sixty-seven individuals (49.0% of the total) had polymicrobial infections. One hundred thirty-one patients (39.8% of the total) underwent endotracheal intubation and mechanical ventilation and 62.6% of them died, compared to 17.7% of the non-intubated patients. Multivariable analysis confirmed a positive correlation between death and increased age (p = 0.05), surgical MDC (p = 0.007), number of microorganisms over the sample mean (p = 0.001), the presence of chronic diseases (p = 0.046), and intubation and mechanical ventilation (p < 0.0001). A positive correlation between intubation and antibiotic-resistant organisms (p = 0.003) was also found. HARIs are still a major public health problem and require constant surveillance due to their severe clinical outcome.

All-Trans Retinoic Acid Effect on Candida albicans Growth and Biofilm Formation.

Candida albicans (C. albicans) is the most common fungal pathogen causing recurrent mucosal and life-threatening systemic infections. The ability to switch from yeast to hyphae and produce biofilm are the key virulence determinants of this fungus. In fact, Candida biofilms on medical devices represent the major risk factor for nosocomial bloodstream infections. Novel antifungal strategies are required given the severity of systemic candidiasis, especially in immunocompromised patients, and the lack of effective anti-biofilm treatments. Retinoids have gained attention recently due to their antifungal properties. MATERIAL AND METHODS: The present study aimed at evaluating the in vitro effects of different concentrations (300 to 18.75 µg/mL) of All-trans Retinoic Acid (ATRA), a vitamin A metabolite, on Candida growth and biofilm formation. RESULTS: ATRA completely inhibited the fungal growth, by acting as both fungicidal (at 300 µg/mL) and fungistatic (at 150 µg/mL) agent. Furthermore, ATRA was found to negatively affect Candida biofilm formation in terms of biomass, metabolic activity and morphology, in a dose-dependent manner, and intriguingly, its efficacy was as that of amphotericin B (AmB) (2-0.12 µg/mL). Additionally, transmission electron microscopy (TEM) analysis showed that at 300 µg/mL ATRA induced plasma membrane damage in Candida cells, confirming its direct toxic effect against the fungus. CONCLUSION: Altogether, the results suggest that ATRA has a potential for novel antifungal strategies aimed at preventing and controlling biofilm-associated Candida infections.

Taking Screenshots of the Invisible: A Study on Bacterial Contamination of Mobile Phones from University Students of Healthcare Professions in Rome, Italy.

Mobile phones (MPs) are commonly used both in the personal and professional life. We assessed microbiological contamination of MPs from 108 students in healthcare professions (HPs), in relation to their demographic characteristics and MPs handling habits, collected by means of a questionnaire. Cultural and biochemical tests were performed, and statistical analyses were carried out. Staphylococci were present in 85% of MPs, Enterococci in 37%, Coliforms in 6.5%; E. coli was never detected. Staphylococcus epidermidis was the most frequently isolated staphylococcal species (72% of MPs), followed by S. capitis (14%), S. saprophyticus, S. warneri, S. xylosus (6%), and by S. aureus (4%). Heterotrophic Plate Counts (HPC) at 37 °C, ranged from 0 to 1.2 × 104 CFU/dm2 (mean = 362 CFU/dm2). In univariate analysis, the male gender only was significantly associated with higher HPCs and enterococcal contamination. Multiple linear regression models explained only 17% and 16% of the HPC 37 °C and staphylococcal load variability, respectively. Developing specific guidelines for a hygienic use of MPs in clinical settings, for preventing cross-infection risks, is advisable, as well as introducing specific training programs to HP students. MPs decontamination procedures could also be implemented in the community.

Viruses of Respiratory Tract: an Observational Retrospective Study on Hospitalized Patients in Rome, Italy.

Respiratory tract infections account for high morbidity and mortality around the world. Fragile patients are at high risk of developing complications such as pneumonia and may die from it. Limited information is available on the extent of the circulation of respiratory viruses in the hospital setting. Most knowledge relates to influenza viruses (FLU) but several other viruses produce flu-like illness. The study was conducted at the University Hospital Policlinico Tor Vergata, Rome, Italy. Clinical and laboratory data from hospitalized patients with respiratory tract infections during the period October 2016-March 2019 were analysed. The retrospective analysis included 17 viral agents detected by FilmArray test and clinical data from medical records and hospital discharge sheets. Models were adjusted for relevant confounders such as clinical severity and risk of death, socio-demographic characteristics and surgical procedures. From a total of 539 specimens analysed, 180 (33.39%) were positive for one or more respiratory viruses. Among them, 83 (46.1 %) were positive for influenza viruses (FLU), 36 (20%) rhino/enteroviruses (RHV/EV), 17 (9.44%) human coronaviruses (HCOV-229E, -HKU1, -NL63, and -OC43), 17 (9.44%) respiratory syncytial virus, 15 (8.33%) human metapneumovirus (HMPV), 8 (4.44%) parainfluenza viruses (PIV) and 4 (2.22%) adenoviruses (ADV). The distribution of viral agents varied across age groups and month of detection. The positive specimens were from 168 patients [102 M, 66 F; median age (range): 64 years (19-93)]. Overall, 40% of them had a high-grade clinical severity and a 27% risk of death; 27 patients died and 22 of them (81.5%) had received a clinical diagnosis of pneumonia. Respiratory viral infections may have a severe course and a poor prognosis in hospitalized patients, due to underlying comorbidities. Monitoring the circulation of respiratory viruses in hospital settings is important to improve diagnosis, prevention and treatment.

Potential mechanism of thymosin-α1-membrane interactions leading to pleiotropy: experimental evidence and hypotheses.

INTRODUCTION: Thymosins have been extracted, characterized, and identified from Thymus. The Thymosins are hormones whose therapeuric applications have seen a recent increase. The action of Thymosin α1 is based on the stimulation of the immune response with a large number of results in a variety of pathologies. The absence of a specific receptor prompted us to investigate the direct interaction with membranes, particularly those exposing phosphatidylserine thus contributing to assess the Thymosin α1's pleiotropy. AREAS COVERED: The interaction with membranes has been studied with a number of models indicating that Thymosin α1 interacts preferentially with negative regions of the membrane (SDS mixed with dodecylphosphocholine) or, better, with vesicles of dipalmitoylphosphatidylcholine with exposed phosphatidylserine. EXPERT OPINION: The study of the role of the membrane in the mechanism of action of Thymosin α1 indicated that probably the first interaction occurs at the membrane level with recognition of negative surface due to the phosphatidylserine exposure. Upon assuming a conformation, with two helices with a disordered tract in between, it diffuses on the membrane surface by lateral diffusion. Then the interaction with membrane receptor(s) causes a membrane complex to be formed, with an activation of a signalling cascade. This can be considered the basis of its pleiotropy. Differences in structuration mechamism of Thymosin ß4 was outlined.

Deciphering cellular biological processes to clinical application: a new perspective for Tα1 treatment targeting multiple diseases.

BACKGROUND: Thymosin alpha 1 (Tα1) is a well-recognized immune response modulator in a wide range of disorders, particularly infections and cancer. The bioinformatic analysis of public databases allows drug repositioning, predicting a new potential area of clinical intervention. We aimed to decipher the cellular network induced by Tα1 treatment to confirm present use and identify new potential clinical applications. RESEARCH DESIGN AND METHODS: We used the transcriptional profile of human peripheral blood mononuclear cells treated in vitro with Tα1 to perform the enrichment network analysis by the Metascape online tools and the disease enrichment analysis by the DAVID online tool. RESULTS: Networked cellular responses reflected Tα1 regulated biological processes including immune and metabolic responses, response to compounds and oxidative stress, ion homeostasis, peroxisome biogenesis and drug metabolic process. Beyond cancer and infections, the analysis evidenced the association with disorders such as kidney chronic failure, diabetes, cardiovascular, chronic respiratory, neuropsychiatric, neurodegenerative and autoimmune diseases. CONCLUSIONS: In addition to the known ability to promote immune response pathways, the network enrichment analysis demonstrated that Tα1 regulates cellular metabolic processes and oxidative stress response. Notable, the analysis highlighted the association with several diseases, suggesting new translational implication of Tα1 treatment in pathological conditions unexpected until now.

Serum thymosin alpha 1 levels in normal and pathological conditions.

INTRODUCTION: Thymosin alpha 1 (Ta1) is a natural occurring peptide hormone that is crucial for the maintenance of the organism homeostasis. It has been chemically synthesized and used in diseases where the immune system is hindered or malfunctioning. AREAS COVERED: Many clinical trials investigate the Ta1 effects in patients with cancer, infectious diseases and as a vaccine enhancer. The number of diseases that could benefit from Ta1 treatment is increasing. To date, questions remain about the physiological basal levels of Ta1 and the most effective dose and schedule of treatment. Evidence is growing that diseases characterized by deregulation of immune and/or inflammatory responses are associated with serum levels of Ta1 significantly lower than those of healthy individuals: to date, B hepatitis, psoriatic arthritis, multiple sclerosis and sepsis. The sputum of cystic fibrosis patients contains lower levels of Ta1 than healthy controls. These data are consistent with the role of Ta1 as a regulator of immunity, tolerance and inflammation. EXPERT OPINION: Low serum Ta1 levels are predictive and/or associated with different pathological conditions. In case of Ta1 treatment, it is crucial to know the patient's baseline serum Ta1 level to establish effective treatment protocols and monitor their effectiveness over time.

Antifungal activity of Cardiospermum halicacabum L. (Sapindaceae) against Trichophyton rubrum occurs through molecular interaction with fungal Hsp90.

INTRODUCTION: Dermatophytosis is a superficial fungal infection limited to the stratum corneum of the epidermis, or to the hair and nails, and constitutes an important public health problem because of its high prevalence and associated morbidity. Dermatophyte fungi, especially 2 species, Trichophyton rubrum and Trichophyton mentagrophytes, are the predominant pathogens. Topical antifungal drugs, mainly azoles or allyamines, are currently used for the treatment of dermatophytoses, although in some cases, such as in nail and hair involvement, systemic treatment is required. However, therapeutic efficacy of current antifungal agents can be limited by their side effects, costs, and the emergence of drug resistance among fungi. Plant extracts represent a potential source of active antimicrobial agents, due to the presence of a variety of chemical bioactive compounds. In the present work, we evaluated in silico and in vitro the antifungal activity of an extract of the medicinal plant Cardiospermum halicacabum against T. rubrum suggesting a potential interaction with Hsp90 as playing an important role in both pathogenicity and drug susceptibility of T. rubrum. METHODS: We investigated in vitro the effect of different concentrations of C. halicacabum (from 500 to 31.25 µg) against a clinical isolate of T. rubrum. Furthermore, using a computational assessment, the interaction between different C. halicacabum active compounds and the fungal Hsp90 was also investigated. RESULTS: Our results indicate a clear-cut antifungal activity of the total plant extract at the highest concentrations (500 and 250 µg). Among all tested C. halicacabum compounds, the luteolin and rutin molecules have been identified in silico as the most important potential inhibitors of Hsp90. Based on these data, luteolin and rutin were also individually assessed for their antifungal activity. Results demonstrate that both substances display an antifungal effect, even if lower than that of the total plant extract. CONCLUSION: Our data indicate a strong fungistatic effect of C. halicacabum against T. rubrum, suggesting its potential therapeutic efficacy in the treatment of dermatophytoses. Additionally, C. halicacabum compounds, and particularly luteolin and rutin, are all possible Hsp90 interactors, explaining their fungistatic activity.

Herpes zoster in frail elderly patients: prevalence, impact, management, and preventive strategies.

Population aging is a worldwide phenomenon with significant and manifold impacts on society. Advanced age correlates with the onset of frailty. In this vulnerable state, the immune response is weakened and a higher susceptibility to infectious diseases is observed. The present narrative review aims to cover the topic of herpes zoster (HZ) and its complications in frail populations. The lifetime risk of developing HZ is estimated at about 20-30%, and the risk increases with age. In older people, HZ can lead to the inability to recover the lifestyle, the interests, and the level of activity that existed before its development. Severity of the disease at presentation and depression are the major correlates of pain burden in patients with acute HZ and postherpetic neuralgia (PHN). The frail elderly need careful assessment prior to treatment initiation and could be affected to a greater extent by treatment-related adverse events. In light of the significant burden caused by HZ and its complications in the frail elderly, the adoption of a preventive strategy appears to be promising, particularly using vaccination in appropriate age- and risk-groups. Although very few vaccine studies consider explicitly the frail elderly as their study population, there is evidence that the live, attenuated vaccine induces significant immunological responses. An adjuvanted recombinant subunit vaccine has recently been approved in Canada, in the United States, in the European Union, and in Japan, and will likely provide additional opportunities for prevention.

High expression of Endogenous Retroviruses from intrauterine life to adulthood in two mouse models of Autism Spectrum Disorders.

Retroelements, such as Human Endogenous Retroviruses (HERVs), have been implicated in many complex diseases, including neurological and neuropsychiatric disorders. Previously, we demonstrated a distinctive expression profile of specific HERV families in peripheral blood mononuclear cells from Autistic Spectrum Disorders (ASD) patients, suggesting their involvement in ASD. Here we used two distinct ASD mouse models: inbred BTBR T+tf/J mice and CD-1 outbred mice prenatally exposed to valproic acid. Whole embryos, blood and brain samples from the offspring were collected at different ages and the expression of several ERV families (ETnI, ETnII-α, ETnII-ß, ETnII-γ, MusD and IAP), proinflammatory cytokines (IL-1ß, IL-6 and TNF-α) and Toll-like receptors (TLR3 and TLR4) was assessed. In the two distinct mouse models analysed, the transcriptional activity of the ERV families was significant higher in comparison with corresponding controls, in whole embryos, blood and brain samples. Also the expression levels of the proinflammatory cytokines and TLRs were significantly higher than controls. Current results are in agreement with our previous findings in ASD children, supporting the hypothesis that ERVs may serve as biomarkers of atypical brain development. Moreover, the changes in ERVs and proinflammatory cytokines expression could be related with the autistic-like traits acquisition in the two mouse models.

Thymosin-α1 expands deficient IL-10-producing regulatory B cell subsets in relapsing-remitting multiple sclerosis patients.

BACKGROUND: B cells are key pathogenic effectors in multiple sclerosis (MS) and several therapies have been designed to restrain B cell abnormalities by directly targeting this lymphocyte population. OBJECTIVES: Moving from our data showing a Toll-like receptor (TLR)7-driven dysregulation of B cell response in relapsing-remitting multiple sclerosis (RRMS) and having found a low serum level of Thymosin-α1 (Tα1) in patients, we investigated whether the addition of this molecule to peripheral blood mononuclear cells (PBMCs) would influence the expansion of regulatory B cell subsets, known to dampen autoimmune inflammation. METHODS: Serum Tα1 level was measured by enzyme immunoassay. Cytokine expression was evaluated by Cytometric Bead Array (CBA), enzyme-linked immunosorbent assay (ELISA), and real-time reverse transcription polymerase chain reaction (RT-PCR). B cell subsets were analyzed by flow cytometry. RESULTS: Tα1 pre-treatment induces an anti-inflammatory status in TLR7-stimulated RRMS PBMC cultures, reducing the secretion of pro-inflammatory interleukin (IL)-6, IL-8, and IL-1ß while significantly increasing the regulatory IL-10 and IL-35. Indeed, Tα1 treatment enhanced expansion of CD19+CD24+CD38hi transitional-immature and CD24low/negCD38hi plasmablast-like regulatory B cell subsets, which likely inhibit both interferon (IFN)-γ and IL-17 production. CONCLUSION: Our study reveals a deficient ability of B cells from MS patients to differentiate into regulatory subsets and unveils a novel anti-inflammatory and repurposing potential for Tα1 in MS targeting B cell response.

Thymosin α1 Interacts with Hyaluronic Acid Electrostatically by Its Terminal Sequence LKEKK.

Thymosin α1 (Tα1), is a peptidic hormone, whose immune regulatory properties have been demonstrated both in vitro and in vivo and approved in different countries for treatment of several viral infections and cancers. Tα1 assumes a conformation in negative membranes upon insertion into the phosphatidylserine exposure as found in several pathologies and in apoptosis. These findings are in agreement with the pleiotropy of Tα1, which targets both normal and tumor cells, interacting with multiple cellular components, and have generated renewed interest in the topic. Hyaluronan (HA) occurs ubiquitously in the extracellular matrix and on cell surfaces and has been related to a variety of diseases, and developmental and physiological processes. Proteins binding HA, among them CD44 and the Receptor for HA-mediated motility (RHAMM) receptors, mediate its biological effects. NMR spectroscopy indicated preliminarily that an interaction of Tα1 with HA occurs specifically around lysine residues of the sequence LKEKK of Tα1 and is suggestive of a possible interference of Tα1 in the binding of HA with CD44 and RHAMM. Further studies are needed to deepen these observations because Tα1 is known to potentiate the T-cell immunity and anti-tumor effect. The binding inhibitory activity of Tα1 on HA-CD44 or HA-RHAMM interactions can suppress both T-cell reactivity and tumor progression.

Clinical features and outcome of hospitalized patients with HSV-1 DNA in the lower respiratory tract.

The aim of this study was to define the clinical impact of Herpes simplex virus-1 (HSV-1) DNA detection in the low respiratory tract of hospitalized patients. Forty-nine patients admitted to the University Hospital Tor Vergata, Rome, Italy, from May 2013 to June 2014, were analysed. Inclusion criteria were the presence or absence of HSV-1 DNA in clinical routine bronchoalveolar lavage (BAL) fluid specimens. Nineteen individuals were positive (cases) and 30 negative (controls) for the presence of HSV-1 DNA. The two groups were matched for age, gender and month of BAL collection. Cases and controls differed significantly according to length of stay in hospital (p=0.027), ICU transfer (p=0.02), disease severity (p=0.003), death (p=0.009), haematological and blood chemistry tests. Among cases, survivors and deceased patients differed significantly regarding ICU transfer (p=0.0001), mechanical ventilation (p=0.0048), disease severity (p=0.028) and risk of death (p=0.013). A trend towards higher HSV-1 loads was observed in the cases who died. These results suggest that detection of HSV-1 DNA in BAL fluid specimens is a marker of disease severity and poor outcome. Further prospective studies are necessary to deepen the clinical significance of HSV-1 DNA detection in the lower respiratory tract of hospitalized patients.

Thymosin α1 Interacts with Exposed Phosphatidylserine in Membrane Models and in Cells and Uses Serum Albumin as a Carrier.

Thymosin α1 is a peptidic hormone with pleiotropic activity and is used in the therapy of several diseases. It is unstructured in water solution and interacts with negative regions of vesicles by assuming two tracts of helical conformation with a structural break between them. This study reports on Thymosin α1's interaction with mixed phospholipids phosphatidylcholine and phosphatidylserine, the negative component of the membranes, by ¹H and natural abundance ¹5N nuclear magnetic resonance (NMR). The results indicate that interaction occurs when the membrane is negatively charged by exposing phosphatidylserine. Moreover, the direct interaction of Thymosin α1 with K562 cells with an overexposure of phosphatidylserine as a consequence of resveratrol-induced apoptosis was conducted. Thymosin α1's interaction with human serum albumin was also investigated by NMR spectroscopy. Steady-state saturation transfer, transfer nuclear Overhauser effect spectroscopy, and diffusion-ordered spectroscopy methodologies all reveal that the C-terminal region of Thymosin α1 is involved in the interaction with serum albumin. These results may shed more light on Thymosin α1's mechanism of action by its insertion in negative regions of membranes due to the exposure of phosphatidylserine. Once Thymosin α1's N-terminus has been inserted into the membrane, the rest may interact with nearby proteins and/or receptors acting as effectors and causing a biological signaling cascade, thus exerting thymosin α1's pleiotropy.

Antitumor effects of the benzophenanthridine alkaloid sanguinarine: Evidence and perspectives.

Historically, natural products have represented a significant source of anticancer agents, with plant-derived drugs becoming increasingly explored. In particular, sanguinarine is a benzophenanthridine alkaloid obtained from the root of Sanguinaria canadensis, and from other poppy Fumaria species, with recognized anti-microbial, anti-oxidant and anti-inflammatory properties. Recently, increasing evidence that sanguinarine exibits anticancer potential through its capability of inducing apoptosis and/or antiproliferative effects on tumor cells, has been proved. Moreover, its antitumor seems to be due not only to its pro-apoptotic and inhibitory effects on tumor growth, but also to its antiangiogenic and anti-invasive properties. Although the precise mechanisms underlying the antitumor activity of this compound remain not fully understood, in this review we will focus on the most recent findings about the cellular and molecular pathways affected by sanguinarine, together with the rationale of its potential application in clinic. The complex of data currently available suggest the potential application of sanguinarine as an adjuvant in the therapy of cancer, but further pre-clinical studies are needed before such an antitumor strategy can be effectively translated in the clinical practice.