Misuse and overuse of antibiotics have contributed in the last decades to a phenomenon known as antibiotic resistance which is currently considered one of the principal threats to global public ...health by the World Health Organization. The aim to find alternative drugs has been demonstrated as a real challenge. Thanks to their biodiversity, insects represent the largest class of organisms in the animal kingdom. The humoral immune response includes the production of antimicrobial peptides (AMPs) that are released into the insect hemolymph after microbial infection. In this review, we have focused on insect immune responses, particularly on AMP characteristics, their mechanism of action and applications, especially in the biomedical field. Furthermore, we discuss the Toll, Imd, and JAK-STAT pathways that activate genes encoding for the expression of AMPs. Moreover, we focused on strategies to improve insect peptides stability against proteolytic susceptibility such as D-amino acid substitutions, N-terminus modification, cyclization and dimerization.
Correcting errors in real time is essential for reliable large-scale quantum computations. Realizing this high-level function requires a system capable of several low-level primitives, including ...single-qubit and two-qubit operations, midcircuit measurements of subsets of qubits, real-time processing of measurement outcomes, and the ability to condition subsequent gate operations on those measurements. In this work, we use a 10-qubit quantum charge-coupled device trapped-ion quantum computer to encode a single logical qubit using the 7,1,3 color code, first proposed by Steane Phys. Rev. Lett. 77, 793 (1996)PRLTAO0031-900710.1103/PhysRevLett.77.793. The logical qubit is initialized into the eigenstates of three mutually unbiased bases using an encoding circuit, and we measure an average logical state preparation and measurement (SPAM) error of 1.7(2)×10^{-3}, compared to the average physical SPAM error 2.4(4)×10^{-3} of our qubits. We then perform multiple syndrome measurements on the encoded qubit, using a real-time decoder to determine any necessary corrections that are done either as software updates to the Pauli frame or as physically applied gates. Moreover, these procedures are done repeatedly while maintaining coherence, demonstrating a dynamically protected logical qubit memory. Additionally, we demonstrate non-Clifford qubit operations by encoding a Tover ¯|+⟩_{L} magic state with an error rate below the threshold required for magic state distillation. Finally, we present system-level simulations that allow us to identify key hardware upgrades that may enable the system to reach the pseudothreshold.
SW480 and SW620 colon carcinoma cell lines derive from primary tumour and lymph-node metastasis of the same patient, respectively. For this reason, these cells represent an ideal system to analyse ...phenotypic variations associated with the metastatic process. In this study we analysed SW480 and SW620 cytoskeleton remodelling by measuring the cells' mechanics and morphological properties using different microscopic techniques. We observed that different specialized functions of cells, i.e. the capacity to metastasize of elongated cells inside the primary tumour and the ability to intravasate and resist shear forces of the stream of cells derived from lymph node metastasis, are reflected in their mechanical properties. We demonstrated that, together with stiffness and adhesion between the AFM tip and the cell surface, cell shape, actin organization and surface roughness are strictly related and are finely modulated by colorectal cancer cells to better accomplish their specific tasks in cancer growth and invasion.
Palladium nanoparticles have been increasingly used in catalytic processes, wastewater treatment, electronics, and biomedicine. However, recent evidence proved that these nanoparticles are able to ...induce adverse effects both in in vitro and in vivo models. Nevertheless, molecular mechanisms underlying the toxic effects are still poorly understood. Therefore, this study aimed to investigate the potential toxicological mechanisms of palladium nanoparticles assessing their effects on normal diploid rat fibroblast and lung carcinoma human epithelial cell lines. Several endpoints such as cell growth, cell cycle progression, DNA damage, induction of apoptosis, reactive oxygen species production and expression of cell cycle regulatory proteins were evaluated. Results showed that palladium nanoparticles inhibited cell growth in a dose- and time-dependent manner in both cell lines, although with a more evident action on fibroblasts. Interestingly, inhibition of cell growth was not associated with the induction of apoptosis. Cell cycle progression was arrested in the G0/G1 phase and DNA damage was evident in both cell lines even if only a slight increase in the intracellular reactive oxygen species levels was detected. These findings provide valuable insight into understanding the molecular mechanisms responsible of palladium nanoparticles toxicity whose identification is essential to define an adequate risk assessment process.
•Palladium nanoparticles inhibited cell growth of Rat-1 and A549 cell lines in a dose- and time-dependent manner;•Palladium nanoparticles caused a progressive arrest of both cell lines in G0/G1 phase of cell cycle without apoptosis;•Palladium nanoparticles were able to induce an increase in DNA single strand breaks in Rat-1 and A549 cell lines;•Exposure to palladium nanoparticles caused a slight increase in the intracellular ROS levels in both cell lines;•Palladium nanoparticles modulated important cell cycle regulatory proteins in Rat-1 and A549 cell lines.
Aim
The pathogenesis of cryptoglandular anal fistula (AF) is still under debate. Tissue inflammation could play a primary role. The pathological process of epithelial mesenchymal transition (EMT) ...might be involved but has never been investigated.
Method
In a prospective pilot study, 12 patients with an AF had a fistulectomy. The excised track was divided into proximal (intrasphincteric) and distal (extrasphincteric) parts which were subjected to standard histopathological examination. The cytokines IL‐8 and IL‐1beta were analysed as markers of inflammation, while EMT was evaluated by expression of TGF‐beta, Vimentin, Zeb‐1, Snail and E‐cadherin. The mRNA and protein expression of these molecules was investigated by real‐time PCR (RT‐PCR), Western blot analysis and immunohistochemistry and was compared with that of the normal adjacent tissue.
Results
Chronic inflammation and granulation tissue and a stratified epithelium were evident on standard histopathological examination. The cytokine IL‐8 was more expressed in the proximal than the distal part of the track (fold increase 4.34 vs 3.60), while the reverse was found for IL‐1beta (fold increase 1.33 vs 2.01); both were more intensely expressed compared with the normal anal mucosa. EMT was demonstrated, in both proximal and distal parts of the track, with an increase of TGF‐beta, Vimentin, Zeb‐1 and Snail and a mean decrease of E‐cadherin. Western blot analysis and immunohistochemistry confirmed the protein expression.
Conclusion
The study suggests that chronic inflammation is present in cryptoglandular fistulas. The inflammatory pattern might be different in the proximal than in the distal part of the fistula track. The cytokines IL‐1beta and IL‐8 could play a possible role in fistula formation. The study demonstrates for the first time the potential importance of EMT in the pathogenesis of cryptoglandular AF.
The widespread industrial application of nanomaterials (NMs) has dramatically increased the likelihood of environmental and occupational exposure of humans to such xenobiotics. This issue, together ...with the increasing public health interest in understanding the effects of chemicals on endocrine system, encouraged to investigate the disruptive potential of NMs on the endocrine function. Therefore, the aim of this study was to evaluate the effects of palladium nanoparticles (Pd-NPs) on the female reproductive system of Wistar rats, intravenously exposed to different doses (0.12, 1.2, and 12 µg/kg), through the assessment of possible quantitative changes in the serum concentrations of several sex hormones. Our results demonstrated that the highest exposure doses significantly reduced the estradiol and testosterone concentrations, while increased the luteinizing hormone levels in treated animals compared to controls. Such alterations are indicative for an abnormal reproductive axis function. However, further investigations are needed to clarify the role of the different NP physicochemical properties in determining such effects, and possible underlining molecular mechanisms, as well as their relevance for the development of diseases in the female reproductive system. Overall, this may be helpful to define accurate risk assessment and management strategies to protect the health of the general and occupational populations exposed to Pd-NPs.
Recently, palladium nanoparticles (PdNPs) have been increasingly used in many industrial sectors, and this has led to a significant release of nano-sized palladium particles into the environment. ...However, despite the increase in occupational and general population exposure, information on the potential adverse effects of these PdNPs is still limited and their impact on the immune system constitutes a major health concern. Therefore, the aim of this study was to investigate the potential adverse effects induced by subchronic intravenous administration of PdNPs on the immune system of female Wistar rats by evaluating alterations in Interleukin (IL)-1α, IL-2, IL-4, IL-6, IL-10, IL-12, granulocyte-macrophage colony-stimulating factor (GM-CSF), Interferon (INF)-γ, and Tumor Necrosis Factor (TNF)-α serum levels. Exposed and control animals were randomly divided into five groups (0, 0.012, 0.12, 1.2, and 12 μg PdNPs per kg body weight) which were treated with repeated intravenous injections of vehicle or PdNPs (on day 1, 30, and 60). Subchronic exposure to PdNPs induced a decreasing trend in serum levels in most of the cytokines investigated, with the highest concentration (12 μg/kg) determining significant inhibitory effects. Overall, these results showed that PdNPs are able to alter cytokine serum levels in subchronically treated Wistar rats, suggesting a possible impact of these xenobiotics on the immune system after long-term exposures.
•Mercury and methyl mercury were determined in Gilthead seabream and European seabass samples.•The fish were collected from the east basin of the Orbetello lagoon, central Italy.•90% Of the ...determined concentrations exceeded the regulative limit.•The concentrations were not related to fish sizes.
Total mercury (Hgtot) and methyl mercury (MeHg) were quantified in several specimens of Dicentrarchus labrax and Sparus aurata from the east basin of the Orbetello lagoon, central Italy. The size of each specimen was recorded to estimate body burdens (BBs); =Hgtot and MeHg were measured in fillets of both species. Hgtot and MeHg in S. aurata ranged between 0.355–1.58 and 0.341–1.53μg/g wet weight (ww), respectively; in D. labrax, their ranges were 0.284–2.54 and 0.214–2.35μg/g ww. Approximately 90% of the concentrations measured exceeded Hgtot regulatory maximum level of 0.5μg/g ww; however, exceedance rate was different in the two species studied. No correlations between specimen size and Hgtot or MeHg BBs were detected in this study.
•Multiplex assay allows a multiple biomarker analysis with a small CSF sample.•CSF CD163 and CHI3L1 baseline level are higher in MS patients than in controls.•In CIS, higher CSF CHI3L1 and CD163 ...levels are associated with conversion to MS.•CSF BAFF levels are lower in OCB+ possibly for higher consumption by B cells.
Multiple sclerosis (MS) is a chronic, immune-mediated, inflammatory, neurodegenerative disorder. Many studies are investigating the potential role of body fluid biomarkers as prognostic factors for early identification of patients presenting with clinical isolated syndrome (CIS) at high risk for conversion to MS or to recognize RRMS patients at high risk for progression.
To evaluate the correlation between levels of BAFF, chitinase 3-like 1 (CHI3L1), sCD163, Osteopontin (OPN), both on serum and cerebral spinal fluid (CSF), and the disease activity and progression. We also want to explore a possible relationship between serological and CSF biomarker's levels.
We enrolled 82 patients between June 2014 and June 2016. Seventy-one received a diagnosis of demyelinating disease of CNS (46 RRMS and 25 CIS), while 11 were affected by other neurological diseases. All patients underwent a neural axis MRI, lumbar puncture and blood samples. Levels of BAFF, CHI3L1, sCD163, OPN on serum and CSF were analyzed by Luminex xMAP system, with a kit 11-plex ad hoc.
The CSF CHI3L1, sCD163 and OPN levels were significantly higher in MS patients than in controls. We did not find significant differences in serum CHI3L1, sCD163 and OPN levels, nor CSF or serum BAFF levels between patient and control groups.
We found significantly higher CSF level of sCD163 and CHI3L1 in all patients’ subgroups compared with controls, while OPN was higher in CIS and RR subgroups. We did not find significant differences for serum and CSF levels of all the markers between patients with or without clinical or radiological disease activity.
CSF sCD163 and CHI3L1 levels was significant higher in CIS patients who converted to MS (p < 0.05).
Using ROC curve analysis, CSF sCD163 resulted the best predictive factor. CSF CHI3L1 and OPN levels resulted useful independent predictors too. Combined ROCs of those three analytes demonstrated a better predictive value, with sCD163 and CHI3L1 resulting as the best combination.
CSF sCD163 CHI3L1 and OPN levels were higher in MS patients whereas serum CHI3L1, sCD163 and OPN levels did not show differences compared with controls. This finding confirms the high CSF specificity with regards to the analysis of processes, inflammatory and non-inflammatory, that occur within the CNS.
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