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Caigua ( Cyclanthera pedata (L.) Schrad.) is an edible plant native of South America, traditionally used for its health-promoting properties. Its cultivation has expanded globally, with a landrace from Camonica Valley (Northern Italy) showing significant potential as a raw material for herbal applications. This study conducted a phytochemical analysis of the fruits and leaves of the Camonica Valley landrace compared to a commercial South American cultivar. Six flavone glycosides were isolated via column chromatography, identified using NMR, and quantified by HPLC. The primary compounds, chrysin-6- C -fucopyranoside and apigenin-6- C -glucopyranoside (isovitexin), were found in both the fruits and leaves of the two cultivars. Quantitative analysis revealed significantly higher levels of flavone glycosides in the leaves of the Camonica Valley cultivar compared to the fruits and the commercial South American cultivar. These findings highlight the potential of this landrace of caigua for herbal, nutraceutical, and food applications.

Introduction. The Triveneto Peritoneal Dialysis (PD) Network aims to bring together doctors and nurses who deal with PD in a collaborative network in which to exchange mutual knowledge and optimize the use of this method of replacing renal function. A topic of particular interest was the management of peritoneal catheter exit-site infection, given the recent publication of the new guidelines of the International Society of Peritoneal Dialysis (ISPD). Materials and methods. The survey concerned the criteria for carrying out nasal swab and exit-site, management of exuberant granulation tissue "Proud Flesh", treatment of exit-site infection (ESI), use of silver dressings, the role of subcutaneous tunnel ultrasound and cuff shaving. Results. All PD centers in the North-East Italy area have joined the survey with at least one operator per centre. There was a wide variability between the indications for performing the exit-site swab. In the presence of ESI, the prevalent approach is that of oral systemic empiric therapy associated (20.0%) or less (28.9%) with topical therapy, and then adapting it in a targeted manner to the culture examination. Discussion. From the discussion of the survey emerged the importance of the ESI as an outcome indicator, which allows us to verify whether our clinical practice is in line with the reference standards. It is essential to know and base our activity on what is indicated in national and international guidelines and to document the events that occur in the patient population of each dialysis unit., (Copyright by Società Italiana di Nefrologia SIN, Rome,Italy.)

"Carciofo di Malegno" is a little-known landrace of Cynara cardunculus subsp. scolymus cultivated in Camonica Valley (northern Italy). The morphological and phytochemical characteristics of this landrace were investigated; furthermore, a species distribution model (MaxEnt algorithm) was used to explore its ecological niche and the geographical area where it could be grown in the future. Due to its spiky shape, "Carciofo di Malegno" was distinct from any other artichoke sample considered, and it appears to be similar to those belonging to the "Spinosi" group. The concentration of chlorogenic acid (497.2 ± 116.0 mg/100 g DW) and cynarine (7.4 ± 1.2 mg/100 g DW) in "Carciofo di Malegno" was comparable to that of the commercial cultivars. In "Carciofo di Malegno," luteolin was detected in a significant amount (9.4 ± 1.5 mg/100 g DW) only in the stems and in the edible parts of the capitula. A MaxEnt distribution model showed that in the coming decades (2040-2060s), the cultivation of this landrace could expand to the pre-Alps and Alps of Lombardy. Climate change may promote the diffusion of "Carciofo di Malegno", contributing to preservation and the enhancement of this landrace and generating sustainable income opportunities in mountain areas through exploring new food or medicinal applications.

Since 72% of rare diseases are genetic in origin and mostly paediatrics, genetic newborn screening represents a diagnostic "window of opportunity". Therefore, many gNBS initiatives started in different European countries. Screen4Care is a research project, which resulted of a joint effort between the European Union Commission and the European Federation of Pharmaceutical Industries and Associations. It focuses on genetic newborn screening and artificial intelligence-based tools which will be applied to a large European population of about 25.000 infants. The neonatal screening strategy will be based on targeted sequencing, while whole genome sequencing will be offered to all enrolled infants who may show early symptoms but have resulted negative at the targeted sequencing-based newborn screening. We will leverage artificial intelligence-based algorithms to identify patients using Electronic Health Records (EHR) and to build a repository "symptom checkers" for patients and healthcare providers. S4C will design an equitable, ethical, and sustainable framework for genetic newborn screening and new digital tools, corroborated by a large workout where legal, ethical, and social complexities will be addressed with the intent of making the framework highly and flexibly translatable into the diverse European health systems., Competing Interests: none., (Copyright: © 2023 Garnier et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

N -Oxyamides of bioactive anionic glycoglycerolipids based on 2- O -β-D-glucosylglycerol were efficiently prepared. However, the oxidation step of the primary hydroxyl group of the glucose moiety in the presence of the N -oxyamide function appeared to be a difficult task that was nevertheless conveniently achieved for the first time by employing a chemoenzymatic laccase/TEMPO procedure. The obtained N -oxyamides exhibited a higher inhibition of proliferation of ovarian carcinoma IGROV-1 cells in serum-free medium than in complete medium, similarly to the corresponding bioactive esters. Stability and serum binding studies indicated that the observed reduced activity of the compounds in complete medium could be mainly due to a binding effect of serum proteins rather than the hydrolytic degradation of glycoglycerolipid acyl chains. Furthermore, the results of the cellular studies under serum-free conditions suggested that the N -oxyamide group could increase the antiproliferative activity of a glycoglycerolipid independently of the presence of the anionic carboxylic group. Cellular studies in other cell lines besides IGROV-1 also support a certain degree of selectivity of this series of compounds for tumor cells with Akt hyperactivation.

Deubiquitinases (DUBs) mediate the removal of ubiquitin from diverse proteins that participate in the regulation of cell survival, DNA damage repair, apoptosis and drug resistance. Previous studies have shown an association between activation of cell survival pathways and platinum-drug resistance in ovarian carcinoma cell lines. Among the strategies available to inhibit DUBs, curcumin derivatives appear promising, thus we hypothesized their use to enhance the efficacy of cisplatin in ovarian carcinoma preclinical models. The caffeic acid phenethyl ester (CAPE), inhibited ubiquitin-specific protease 8 (USP8), but not proteasomal DUBs in cell-free assays. When CAPE was combined with cisplatin in nine cell lines representative of various histotypes a synergistic effect was observed in TOV112D cells and in the cisplatin-resistant IGROV-1/Pt1 variant, both of endometrioid type and carrying mutant TP53. In the latter cells, persistent G1 accumulation upon combined treatment associated with p27 kip1 protein levels was observed. The synergy was not dependent on apoptosis induction, and appeared to occur in cells with higher USP8 levels. In vivo antitumor activity studies supported the advantage of the combination of CAPE and cisplatin in the subcutaneous model of cisplatin-resistant IGROV-1/Pt1 ovarian carcinoma as well as CAPE activity on intraperitoneal disease. This study reveals the therapeutic potential of CAPE in cisplatin-resistant ovarian tumors as well as in tumors expressing USP8., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Platinum (Pt) drugs, including cisplatin, are widely used for the treatment of solid tumors. Despite the clinical success, side effects and occurrence of resistance represent major limitations to the use of clinically available Pt drugs. To overcome these problems, a variety of derivatives have been designed and synthetized. Here, we summarize the recent progress in the development of Pt(II) and Pt(IV) complexes with bioactive ligands. The development of Pt(II) and Pt(IV) complexes with targeting molecules, clinically available agents, and other bioactive molecules is an active field of research. Even if none of the reported Pt derivatives has been yet approved for clinical use, many of these compounds exhibit promising anticancer activities with an improved pharmacological profile. Thus, planning hybrid compounds can be considered as a promising approach to improve the available Pt-based anticancer agents and to obtain new molecular tools to deepen the knowledge of cancer progression and drug resistance mechanisms., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The follow-up automated peritoneal dialysis (APD) patients has been recently improved as data can be transmitted remotely to an internet cloud. The introduction of remote patient monitoring (RPM) technologies also allows a better clinical control and tailoring of dialysis treatment through a web-based software (Claria-Sharesource Baxter). The aim of the present study is to determine the impact of RPM in a single center, both in clinical and organizational terms, compared to traditional technologies. We studied 26 prevalent APD patients aged 69±13 years, observing them for a period of six months while using the traditional technology and then further six months using the new technology. The patients had been on dialysis for 9 months before the start of the study and a relevant portion of them lived in mountainous or hilly areas. Our study shows an increase in the number of proactive calls from the center to the patients, a reduction of anxiety in patients and caregivers, an earlier detection of clinical problems, a reduction of unscheduled (urgent) visits and finally a reduction of hospitalizations after the adoption of RPM software. In our experience, the RPM system showed a good performance and a simple interface, allowing for the precise assessment of daily APD. Furthermore, RPM system improved the interaction between patients and healthcare providers, with a significant benefit in terms of safety and of care quality., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

3-(2-Haloacyl)-2-oxazolidinones were shown to react with enals in an asymmetric SmI 2 -promoted Reformatsky reaction to give stereochemically well-defined 3-hydroxy-4-alkenyl- and 3-hydroxy-2-methyl-4-alkenyl imides. Chirality transfer of the Evans ( S )-oxazolidinone unit via a Zimmerman-Traxler-like transition state resulted in Reformatsky products with a relative syn -configuration. The absolute configuration of compounds obtained is opposite to the corresponding products obtained via aldol addition of boron enolates to enals using the same Evans oxazolidinones.

Crop disease management often implies repeated application of fungicides. However, the increasing emergence of fungicide-resistant pathogens requires their rotation or combined use. Tank-mix combinations using fungicides with different modes of action are often hard to manage by farmers. An alternative and unexploited strategy are bifunctional fungicides, i.e. compounds resulting from conjugation of the pharmacophores of fungicides with different mechanisms of action. In this paper we describe a new approach to antifungal treatments based on the synthesis of dual agents, obtained by merging the strobilurin and succinate dehydrogenase inhibitor pharmacophores into a new entity. The compounds were tested against important fungal plant pathogens and showed good inhibition of Pyricularia oryzae and Sclerotinia sclerotiorum with activity comparable to commercial fungicides. The inhibition of the cytochrome bc1 and the succinate dehydrogenase enzyme activity confirmed that the new molecules are endowed with a dual mechanism of action. These results were further supported by molecular modelling which showed that selected compounds form stable complexes with both cytochrome b subunit and succinate dehydrogenase enzyme. This work can be considered an important first step towards the development of novel dual-action agents with optimized structure and improved interaction with the targets.

Keratinocytes represent the first line of defense against pathogens in the skin and have important roles in initiating and regulating inflammation during infection and autoimmunity. Here we investigated the role of miR-146a in the regulation of the innate immune response of keratinocytes. Toll-like receptor 2 (TLR2) stimulation of primary human keratinocytes resulted in an NF-κB- and mitogen-activated protein kinase-dependent upregulation of miR-146a expression, which was surprisingly long lasting, contrasting with the rapid and transient induction of inflammatory mediators. Overexpression of miR-146a significantly suppressed the production of IL-8, CCL20, and tumor necrosis factor-α, which functionally suppressed the chemotactic attraction of neutrophils by keratinocytes. Inhibition of endogenous miR-146a induced the production of inflammatory mediators even in nonstimulated keratinocytes, and potentiated the effect of TLR2 stimulation. Transcriptomic profiling revealed that miR-146a suppresses the expression of a large number of immune-related genes in keratinocytes. MiR-146a downregulated interleukin-1 receptor-associated kinase 1 and TNF receptor-associated factor 6, two key adapter molecules downstream of TLR signaling, and suppressed NF-κB promoter-binding activity as shown by promoter luciferase experiments. Together, these data identify miR-146a as a regulatory element in keratinocyte innate immunity, which prevents the production of inflammatory mediators under homeostatic conditions and serves as a potent negative feedback regulator after TLR2 stimulation.

Introduction: Surgical resection represents the only therapeutic action having a radical intent for the treatment of resectable esophageal neoplasms. Minimally invasive esophagectomy for esophageal cancer is being more and more frequently performed. Few cases of esophagectomy after pneumonectomy have been described in the literature, and, to our knowledge, none of them was performed by the minimally invasive technique., Subject and Methods: A 77-year-old woman, who had undergone left thoracotomic pneumonectomy due to squamous cell lung cancer 2 years before, underwent minimally invasive esophagectomy because of esophageal cancer at the authors' institution. The intervention was performed by right thoracoscopic esophageal mobilization with the patient in the prone position, followed by the laparoscopic and cervicotomic stages, with cervical anastomosis., Results: Total operative time was 230 minutes. Intensive care unit stay was 1 day, followed by a hospital stay of 13 days. We did not observe any major postoperative complication., Conclusions: Minimally invasive esophagectomy with thoracoscopic esophageal mobilization in the prone position is a valid option in the treatment of esophageal cancer and may be feasible in previously left pneumonectomized patients.

We show that a fully functional endocannabinoid system is present in primary human melanocytes (normal human epidermal melanocyte cells), including anandamide (AEA), 2-arachidonoylglycerol, the respective target receptors (CB(1), CB(2), and TRPV1), and their metabolic enzymes. We also show that at higher concentrations AEA induces normal human epidermal melanocyte apoptosis (∼3-fold over controls at 5 μM) through a TRPV1-mediated pathway that increases DNA fragmentation and p53 expression. However, at lower concentrations, AEA and other CB(1)-binding endocannabinoids dose-dependently stimulate melanin synthesis and enhance tyrosinase gene expression and activity (∼3- and ∼2-fold over controls at 1 μM). This CB(1)-dependent activity was fully abolished by the selective CB(1) antagonist SR141716 or by RNA interference of the receptor. CB(1) signaling engaged p38 and p42/44 mitogen-activated protein kinases, which in turn activated the cyclic AMP response element-binding protein and the microphthalmia-associated transcription factor. Silencing of tyrosinase or microphthalmia-associated transcription factor further demonstrated the involvement of these proteins in AEA-induced melanogenesis. In addition, CB(1) activation did not engage the key regulator of skin pigmentation, cyclic AMP, showing a major difference compared with the regulation of melanogenesis by α-melanocyte-stimulating hormone through melanocortin 1 receptor.

Background: Surgical resection is the mainstay treatment for resectable esophageal cancer. Minimally invasive esophagectomy is performed with increasing frequency and proves to be a safe and effective surgical alternative to the open technique. Minimally invasive esophagectomy using thoracoscopic esophageal mobilization with the patient in prone position seems to offer some advantages with regard to surgeon ergonomics and clinical outcome., Methods: Between July 2005 and September 2010, 46 patients (35 men and 11 women) underwent minimally invasive esophagectomy in the prone position at the authors' institution. Three patients had previously undergone a thoracic intervention (one patient had previously undergone left pneumonectomy because of lung cancer). The preoperative indication was squamous cell carcinoma for 35 patients and adenocarcinoma for 11 patients. In one case, the histology of the biopsy samples showed a squamous cell carcinoma with neuroendocrine differentiation. Neoadjuvant treatment was administered to 15 patients., Results: All 46 patients underwent esophagectomy using minimally invasive thoracic mobilization of the esophagus with the patient in prone position. The abdominal stage of intervention was performed by laparoscopy for 37 patients and by laparotomy for 9 patients. No thoracotomic conversion was performed. In all cases, a cervical end-to-side anastomosis was performed using a circular stapler. The mean operative time was 263 min. The median intensive care unit stay was 2 days, and the median postoperative hospital stay was 15 days. The mean number of procured lymph nodes was 13. The perioperative morbidity rate was 37%, and the perioperative mortality rate was 4.4%., Conclusions: Minimally invasive esophagectomy is safe and technically feasible. It entails a lower mortality rate and a shorter hospital stay than those reported in most open series. Thoracoscopy with the patient in prone position offers results comparable with those obtained using other minimally invasive techniques regarding the number of procured lymph nodes. This technique shows considerable advantages such as improved surgeon ergonomics, increased operative field exposure, and satisfactory respiratory results.

Centrosomes are closely associated with the nuclear envelope (NE) throughout the cell cycle and this association is maintained in prophase when they separate to establish the future mitotic spindle. At this stage, the kinetochore constituents CENP-F, NudE, NudEL, dynein, and dynactin accumulate at the NE. We demonstrate here that the N-terminal domain of the nuclear pore complex (NPC) protein Nup133, although largely dispensable for NPC assembly, is required for efficient anchoring of the dynein/dynactin complex to the NE in prophase. Nup133 exerts this function through an interaction network via CENP-F and NudE/EL. We show that this molecular chain is critical for maintaining centrosome association with the NE at mitotic entry and contributes to this process without interfering with the previously described RanBP2-BICD2-dependent pathway of centrosome anchoring. Finally, our study reveals that tethering of centrosomes to the nuclear surface at the G2/M transition contributes, along with other cellular mechanisms, to early stages of bipolar spindle assembly.

We previously demonstrated that a fraction of the human Nup107-160 nuclear pore subcomplex is recruited to kinetochores at the onset of mitosis. However, the molecular determinants for its kinetochore targeting and the functional significance of this localization were not investigated. Here, we show that the Nup107-160 complex interacts with CENP-F, but that CENP-F only moderately contributes to its targeting to kinetochores. In addition, we show that the recruitment of the Nup107-160 complex to kinetochores mainly depends on the Ndc80 complex. We further demonstrate that efficient depletion of the Nup107-160 complex from kinetochores, achieved either by combining siRNAs targeting several of its subunits excluding Seh1, or by depleting Seh1 alone, induces a mitotic delay. Further analysis of Seh1-depleted cells revealed impaired chromosome congression, reduced kinetochore tension and kinetochore-microtubule attachment defects. Finally, we show that the presence of the Nup107-160 complex at kinetochores is required for the recruitment of Crm1 and RanGAP1-RanBP2 to these structures. Together, our data thus provide the first molecular clues underlying the function of the human Nup107-160 complex at kinetochores.

Polyhydroxybutyrate (PHB) is the most studied among a wide variety of polyhydroxyalkanoates, bacterial biodegradable polymers known as potential substitutes for conventional plastics. This work aimed at evaluating the use of enzymes to recover and purify the PHB produced by Ralstonia eutropha DSM545. Screening experiments allowed the selection of trypsin, bromelain and lysozyme among six enzymes, based on their efficiency in lysing cells of a non-PHB producing R. eutropha strain. Then, process conditions for high efficiency in PHB purification from the DSM545 cells were searched for the enzymes previously selected. The best result was achieved with 2.0% of bromelain (enzyme mass per biomass), equivalent to 14.1 U ml(-1), at 50 degrees C and pH 9.0, resulting in 88.8% PHB purity. Aiming at improving the process efficiency and reducing the enzyme cost, experiments were carried out with pancreatin, leading to 90.0% polymer purity and an enzyme cost three times lower than the one obtained with bromelain. The molecular mass analysis of PHB showed no polymer degradation. Therefore, this work demonstrates the potential of using enzymes in order to recover and purify PHB and bacterial biopolymers in general.

Using a genetic screen, we have identified a previously uncharacterized Saccharomyces cerevisiae open reading frame (renamed PML39) that displays a specific interaction with nucleoporins of the Nup84 complex. Localization of a Pml39-green fluorescent protein (GFP) fusion and two-hybrid studies revealed that Pml39 is mainly docked to a subset of nuclear pore complexes opposite to the nucleolus through interactions with Mlp1 and Mlp2. The absence of Pml39 leads to a specific leakage of unspliced mRNAs that is not enhanced upon MLP1 deletion. In addition, overexpression of PML39-GFP induces a specific trapping of mRNAs transcribed from an intron-containing reporter and of the heterogenous nuclear ribonucleoprotein Nab2 within discrete nuclear domains. In a nup60delta mutant, Pml39 is mislocalized together with Mlp1 and Mlp2 in intranuclear foci that also recruit Nab2. Moreover, pml39delta partially rescues the thermosensitive phenotypes of messenger ribonucleoparticles (mRNPs) assembly mutants, indicating that PML39 deletion also bypasses the requirement for normally assembled mRNPs. Together, these data indicate that Pml39 is an upstream effector of the Mlps, involved in the retention of improper mRNPs in the nucleus before their export.

The Authors, through the study of their patients, and comparing it to other reports, help to further define the meaning, prognosis and type of treatment of local recurrences (LR) in breast cancer. They study 25 cases of LR after 238 operations on which regular clinical follow-up was carried out. They consider the various prognostic indicators for LR, the types of treatment and the results which are reached. Median survival after LR treatment was significantly better in patients N- (49 months vs 7 months in N+: p = 0.004). LR was more frequent when primary tumor was situated in inner quadrants; only 36% of their cases depend on primaries of the upper outer quadrant. An aggressive treatment (surgery, radiotherapy, chemotherapy) insures a better survival even if primary cancer is N+ greater than 3. The importance for prognosis of lymphnodal status is confirmed. Possible explanations are presented regarding the relatively lower incidence in upper outer quadrant cancers. An aggressive treatment of LR is suggested, specially when prognostic indicators are unfavourable: LR is very often a sign of systemic relapse of illness, particularly when it occurs after a short disease-free interval.