Mitochondrial permeabilization engages NF-kappa B-dependent anti-tumour activity under caspase deficiency

Apoptosis represents a key anti-cancer therapeutic effector mechanism. During apoptosis, mitochondrial outer membrane permeabilization (MOMP) typically kills cells even in the absence of caspase activity. Caspase activity can also have a variety of unwanted consequences that include DNA damage. We therefore investigated whether MOMP-induced caspase-independent cell death (CICD) might be a better way to kill cancer cells. We find that cells undergoing CICD display potent pro-inflammatory effects relative to apoptosis. Underlying this, MOMP was found to stimulate NF-κB activity through the downregulation of inhibitor of apoptosis proteins. Strikingly, engagement of CICD displays potent anti-tumorigenic effects, often promoting complete tumour regression in a manner dependent on intact immunity. Our data demonstrate that by activating NF-κB, MOMP can exert additional signalling functions besides triggering cell death. Moreover, they support a rationale for engaging caspase-independent cell death in cell-killing anti-cancer therapies

Annealing of bismuth telluride-based thick films by laser irradiation

Interest towards fabrication and post-processing of thermoelectric micro-sized devices has increased in recent years. The coupling of inexpensive deposition technologies and fast laser treatments on “as-deposited” films is an attractive solution for industrial scalability. In this work, we propose an approach never reported before in literature: the utilization of a ns-pulsed active fibre laser to directly densify p-type bismuth telluride-based thick films deposited on silicon. A feasibility study was conducted on the material to determine optimal laser parameters: the treated products were characterized, and it was concluded that a value of laser fluence as low as 4.5 mJ cm−2 is sufficient for densification. The material resulted cracked after the laser treatment, and it was demonstrated by SEM and profilometric analyses that shrinking occurs and sintering necks are formed; further, the arising of second phases after annealing was excluded by means of XRD analysis. Envisioning an industrial large area process with linear diode arrays source, a prediction of the laser power requirements to irradiate 1 mm2 films in selected conditions is presented. More extensive studies will be performed to determine a narrower parameters window and determine a relationship between the film thickness and laser parameters for future applications to as-deposited films

Mesalamine-induced myopericarditis in children: a case report and a short revision of the literature

Mesalamine has a central role in the treatment of inflammatory bowel disease (IBD). Myocarditis and/or pericarditis are rare and severe side effects of mesalamine-containing drugs. We describe the case of a 14 years old boy, developing myopericarditis two weeks after starting mesalamine treatment for ulcerative colitis (UC). The adverse effect had a massive impact on the left ventricular function and required immedi-ate intervention. Once identified as possible causative agent, mesalamine was discontinued with subsequent improvement of the clinical symptoms and laboratory findings. No recurrency nor sequelae were detected at the cardiological follow up. Mesalamine is a widely used drug for pediatric IBD treatment, although its effect on heart tissues is a rare but potentially fatal adverse reaction. At the time of presentation, in April 2021, 10 pediatric cases were reported in literature (2 children and 8 adolescents). Of them, 60% were treated with me-salamine for UC and 40% for Chron’s disease (CD). Chest pain and fever were the most common symptoms at presentation (100% and 50% respectively), cough and fatigue were less represented. None of the patients developed sequelae at follow up. In patients treated with mesalamine early recognition of side effects, drug discontinuation and accurate therapy are crucial to prevent progression of the inflammation and to avoid adverse cardiovascular outcomes. (www.actabiomedica.it)

Caratterizzazione ad usura di rivestimenti PVD con e senza laser texturing

Il processo di laser texturing (LST) è una delle tecniche più promettenti nel campo delle microlavorazioni superficialiin quanto consente di ottenere un eccellente controllo della forma e delle dimensioni delle microcavitàprodotte ed è estremamente veloce e senza ricadute dannose per l’ambiente. Recentemente si è assistito allosviluppo di diversi lavori nei quali il laser è stato impiegato per migliorare il comportamento tribologico di componentimeccanici in materiale metallico. Le microcavità, realizzate per ablazione dal fascio laser sulla superficiedi interesse, infatti hanno diversi aspetti positivi da questo punto di vista perché generano un sistema diffusodi microspinte idrodinamiche sulla superficie e agiscono come riserve di lubrificante da una parte e come trappoleper i detriti di usura dall’altra, ritardando così, l’innesco di meccanismi di usura da terzo corpo. Nel presentelavoro si presentano i risultati di una sperimentazione volta a valutare l’effetto dell’introduzione di unalavorazione superficiale di texturing laser sulla superficie di riporti PVD in TiN. Per il texturing è stata utilizzatauna sorgente laser in fibra innovativa ad alta efficienza che ha consentito, una volta ottimizzati i parametridi processo, di ottenere dimensioni controllate delle microcavità, una buona geometria delle stesse e di evitarela presenza di residui di lavorazione anche sui coating ceramici oggetto dello studio. I test di usura in condizionidi strisciamento lubrificato con alto carico applicato e bassa velocità relativa , sono stati condotti sul rivestimentoTiN microlavorato e per confronto sul tal quale e su un rivestimento autolubrificante commerciale,il WC/C. I risultati ottenuti mostrano un marcato incremento delle prestazioni a usura per il rivestimento lasercon texturing (fino al 50% di riduzione del volume di usura) e l’assenza di significativi danneggiamenti del rivestimentoin presenza delle microcavità e delle sollecitazioni di usura applicate. Nel breve futuro si eseguiràpertanto un approfondimento ulteriore per valutare anche l’economia di scala del ciclo di lavorazione

Corrosion behavior and surface properties of PVD coatings for mold technology applications

Chrome plating is still one of the best solutions to coat martensitic steel used in the molding of plastics and rubbers. However, current stringent regulations on environmental impact call for more sustainable processes. In the present work, some physical vapor deposition (PVD) nitride coatings were produced on X155CrMoV12 steel and characterized in terms of both corrosion behavior and surface properties. Results indicated that titanium-based PVD coatings could be a valuable alternative to chromium-based coatings as they exhibited a good compromise between corrosion and surface properties. AlTiN and TiN PVD coatings exhibited adequate hardness for plastic mold applications, with AlTiN reaching hardness as high as 2000 HV. Moreover, the critical loads and adhesion properties were found to be definitely better than those of chromium-based coatings. From a corrosion point of view, the presence of multilayers in AlTiN did not seem to be beneficial as the breakdown potential for TiN (single layer) was ca. 1.1 V vs. saturated calomel electrode (SCE) compared to 0.85 V vs. SCE for AlTiN in aggressive media (NaCl)

Modification of Pure Zinc Surface for Biomedical Applications: The Effect of Oxygen Plasma Immersion Ion Implantation on Tuning the Degradation Rate

Zinc is a high-potential metal for biodegradable implants. The study of the surface properties, even if at a fundamental level, is of central importance because the surface is the place where electrochemical, physical, and biological interactions take place; this is critical especially for biomedical applications, in which these interactions affect each other. The present work investigates the effect of low-energy oxygen implantation, in the range of − 1 to − 5 kV, for different durations on commercially pure Zn, whose surface had been mechanically polished. The characterization of the as-received and implanted surface was carried out with standard and high-resolution electron microscopy, energy dispersive X-ray spectroscopy, sessile drop contact angle, X-ray photoelectron spectroscopy, and potentiodynamic tests. The plasma-treated surface showed distinct features related to the process parameters, such as the formation of surface waves and oxide agglomerates. The formation of an O-ric..

Extracellular volume measured by whole body CT scans predicts chronic cardiotoxicity in breast cancer patients treated with neoadjuvant therapies based on anthracyclines: A retrospective study

introduction: neoadjuvant chemotherapies for breast cancer (BC) are effective but potentially cardiotoxic, and expose long survivors at risk of chemotherapy-related cardiac dysfunction (CTRCD). Unfortunately, early screening for CTRCD has actual diagnostic limits. myocardial extracellular volume (mECV) is a radiological marker used in cardiac CT scans and cardiac magnetic resonance for diagnosis and follow-up of CTRCD. It can be measured in whole-body CT (WB-CT) scan, routinely performed in patients at high risk of relapse, to evaluate CTRCD occurrence during oncological follow-up. methods: 82 WB-CT scans were examined at baseline (T0) and during oncological follow-up at first year (T1) and fifth year (T5) after the end of neoadjuvant treatment. mECV was measured at 1 min (PP) and 5 min (DP) after contrast injection. 31 echocardiograms were retrieved in T1 to perform a linear correlation between mECV and left ventricular ejection fraction (LVEF). results: mECV values in T0 were similar between the two groups both in PP and in DP. Significant results were found for PP values in T1 (37.0 % vs 32 %, p = 0.0005) and in T5 (27.2 % vs 31.2 %, p = 0.025). a cut-off value of 35 % in PP proved significant in T1 (OR = 12.4, p = 0.004), while mECV was inversely correlated with LVEF both in PP (adj-S = -3.54, adj-p = 0.002) and in DP (adj-S = -2.51, adj-p = 0.0002), suggesting a synergistic action with the age at diagnosis (p < 0.0001, respectively). conclusions: WB-CT scans performed during oncological reassessment in patients at high-risk of recurrence could be used for CTRCD screening in cardiovascular low-risk patients, especially in aging patients with mECV values above 35 %

DNA damage and transcriptional regulation in iPSC-derived neurons from Ataxia Telangiectasia patients

Abstract Ataxia Telangiectasia (A-T) is neurodegenerative syndrome caused by inherited mutations inactivating the ATM kinase, a master regulator of the DNA damage response (DDR). What makes neurons vulnerable to ATM loss remains unclear. In this study we assessed on human iPSC-derived neurons whether the abnormal accumulation of DNA-Topoisomerase 1 adducts (Top1ccs) found in A-T impairs transcription elongation, thus favoring neurodegeneration. Furthermore, whether neuronal activity-induced immediate early genes (IEGs), a process involving the formation of DNA breaks, is affected by ATM deficiency. We found that Top1cc trapping by CPT induces an ATM-dependent DDR as well as an ATM-independent induction of IEGs and repression especially of long genes. As revealed by nascent RNA sequencing, transcriptional elongation and recovery were found to proceed with the same rate, irrespective of gene length and ATM status. Neuronal activity induced by glutamate receptors stimulation, or membrane depolarization with KCl, triggered a DDR and expression of IEGs, the latter independent of ATM. In unperturbed A-T neurons a set of genes (FN1, DCN, RASGRF1, FZD1, EOMES, SHH, NR2E1) implicated in the development, maintenance and physiology of central nervous system was specifically downregulated, underscoring their potential involvement in the neurodegenerative process in A-T patients

Main roads and land cover shaped the genetic structure of a Mediterranean island wild boar population

Patterns of genetic differentiation within and among animal populations might vary due to the simple effect of distance or landscape features hindering gene flow. An assessment of how landscape connectivity affects gene flow can help guide man -agement, especially in fragmented landscapes. Our objective was to analyze popu-lation genetic structure and landscape genetics of the native wild boar (Sus scrofa meridionalis) population inhabiting the island of Sardinia (Italy), and test for the ex -istence of Isolation- by- Distance (IBD), Isolation- by- Barrier (IBB), and Isolation- by- Resistance (IBR). A total of 393 Sardinian wild boar samples were analyzed using a set of 16 microsatellite loci. Signals of genetic introgression from introduced non- native wild boars or from domestic pigs were revealed by a Bayesian cluster analysis includ -ing 250 reference individuals belonging to European wild populations and domestic breeds. After removal of introgressed individuals, genetic structure in the popula -tion was investigated by different statistical approaches, supporting a partition into five discrete subpopulations, corresponding to five geographic areas on the island: north- west (NW), central west (CW), south- west (SW), north- central east (NCE), and south- east (SE). To test the IBD, IBB, and IBR hypotheses, we optimized resistance surfaces using genetic algorithms and linear mixed- effects models with a maximumlikelihood population effects parameterization. Landscape genetics analyses revealedthat genetic discontinuities between subpopulations can be explained by landscape elements, suggesting that main roads, urban settings, and intensively cultivated areas are hampering gene flow (and thus individual movements) within the Sardinian wild boar population. Our results reveal how human-transformed landscapes can affect genetic connectivity even in a large-sized and highly mobile mammal such as the wild boar, and provide crucial information to manage the spread of pathogens, including the African Swine Fever virus, endemic in Sardinia

Clinical presentation of celiac disease and diagnosis accuracy in a single-center european pediatric cohort over 10 years

(1) Background: Changes in the clinical presentation of celiac disease (CD) in children have been reported. The guidelines of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) allow esophagogastroduodenoscopy (EGD) with biopsies to be avoided under specific circumstances. We aimed to assess the clinical picture of pediatric CD patients at diagnosis and to validate ESPGHAN non-biopsy criteria. (2) Methods: Patients with suspected CD or undergoing screening from 2004 to 2014 at the University Hospital in Modena, Italy were enrolled. The accuracy of ESPGHAN non-biopsy criteria and modified versions were assessed. (3) Results: In total, 410 patients were enrolled, of whom 403 were considered for analysis. Of the patients considered, 45 were asymptomatic and diagnosed with CD (11.2%) while 358 patients (88.2%) were symptomatic, of whom 295 were diagnosed with CD. Among symptomatic CD patients, 57 (19.3%) had gastrointestinal symptoms, 98 (33%) had atypical symptoms and 140 (47.4%) had both. No difference was found for the presence of gastrointestinal symptoms at different ages. The non-biopsy ESPGHAN criteria yielded an accuracy of 59.4% with a positive predictive value (PPV) of 100%; 173 out of 308 EGD (56.2%) could have been avoided. The modified 7× and 5× upper limit of normal cut-offs for IgA anti tissue-transglutaminase reached 60.7% and 64.3% of EGD avoided, respectively. (4) Conclusions: Over 10 years, late age at diagnosis and increased rates of atypical CD presentation were found. ESPGHAN non-biopsy criteria are accurate for CD diagnosis and allow half of unneeded EGD to be avoided. Modified versions allowed sparing a greater number of EGD