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The exposure of humans to microplastics through food is a topic of great interest. Foods of marine origin, such as fish and salt, have been the most extensively studied in this regard. Conversely, foods considered less likely to be contaminated (such as dairy products) have been investigated to a lesser extent. This is the first study addressing the occurrence of microplastics in cheese. In this paper, we report the first analytical approach for cheese preparation, before a chemical analysis of microplastics in cheese was performed. Therefore, the most suitable digestion methods were investigated. Alkaline digestion (i.e., KOH 5 M, 50 °C, 48 h) achieved a digestion efficiency of 97.5 ± 0.8%. To assess the feasibility of the preparative method proposed, a recovery rate of spiked polystyrene microbeads (~10 µm) of 98.5 ± 0.4% was determined. Further, the effects of the digestion agent on the microbeads were also investigated. To confirm whether the preparative method allows for the confirmation of the plastic-nature of microparticles, a qualification of spiked microplastics (polystyrene, 150 µm, and polyethylene terephthalate, 300 µm) was performed using pyrolysis–gas chromatography–mass spectrometry.

An economy based on renewable energy sources is the hallmark of responsible companies. Climate policy and energy crisis commitments have led to a search for alternative ways to produce energy. Bioenergy is considered the most consistent renewable energy source due to its economic and environmental benefits. Biogas and biomethane are promising forms of renewable energy derived from widely available evergreen raw materials. Agricultural, animal, industrial and food wastes are excellent substrates used to produce clean and sustainable energy in a circular economy context. Their conversion into biogas and biomethane through the anaerobic digestion (AD) process is an efficient solution to the treatment of waste of different origins. The production and use of biomethane favor important environmental advantages, such as the reduction in greenhouse gas emissions compared with those deriving from the use of conventional fossil fuels. This review would like to highlight modern trends and approaches to evaluate processes and strategies to control biogas and biomethane production. In particular, the use of livestock waste for the digestion process and the reuse of the by-product as fertilizer, as well as the potential development of biogas and biomethane as prospects for the improvement and optimization of renewable energy sources, are discussed.

With the clear need for better cancer treatment, naturally occurring molecules represent a powerful inspiration. Recently, curcumin has attracted attention for its pleiotropic anticancer activity in vitro, especially against colorectal and prostate cancer cells. Unfortunately, these encouraging results were disappointing in vivo due to curcumin’s low stability and poor bioavailability. To overcome these issues, herein, the synthesis of eight new pyrimidine–curcumin derivatives is reported. The compounds were fully characterized (1H/13C NMR (Nuclear Magnetic Resonance), LC-MS (Liquid Chromatography-Mass Spectrometri), UV-Vis spectroscopy), particularly their acid/base behavior; overall protonation constants were estimated, and species distribution, as a function of pH, was predicted, suggesting that all the compounds are in their neutral form at pH 7.4. All the compounds were extremely stable in simulated physiological media (phosphate-buffered saline and simulated plasma). The compounds were tested in vitro (48 h incubation treatment) to assess their effect on cell viability in prostate cancer (LNCaP and PC3) and colorectal cancer (HT29 and HCT116) cell lines. Two compounds showed the same anti-proliferative activity as curcumin against HCT116 cells and improved cytotoxicity against PC3 cells.

Astragalus membranaceus (Fisch.) Bunge root is used as herbal medicine for its immunomodulating activities in Chinese medicine. Recently, beneficial properties of A. membranaceus on allergic diseases have been proposed. Here we investigated the role of a commercial extract of A. membranaceus, standardized to 16% polysaccharides, in regulating the immune-inflammatory response in vitro and in vivo and its therapeutic application in asthma. A. membranaceus extract inhibited prostaglandin E2 and leukotriene C4 production in stimulated J774 and peritoneal macrophages, respectively. The extract also reduced interlukin-1β, tumor necrosis factor-α, and nitrite production, affecting inducible nitric oxide synthase expression. In vivo experiments confirmed the anti-inflammatory properties of A. membranaceus, as evident by a reduction in zymosan-induced peritoneal cellular infiltration and pro-inflammatory mediator production. The efficacy of A. membranaceus extract in modulating the immune response was confirmed in a model of allergic airway inflammation. Extracts improve lung function by inhibiting airway hyperresponsiveness, airway remodeling, and fibrosis. Its anti-asthmatic effects were further sustained by inhibition of the sensitization process, as indicated by a reduction of ovalbumin-induced IgE levels and the mounting of a Th2 immune response. In conclusion, our data demonstrate the anti-inflammatory properties of the commercial extract of A. membranaceus and its beneficial effects on asthma feature development.

Indoor air quality has become a topic of great concern. Burning incense has recently been identified as one of the primary sources of volatile organic compounds, specifically benzene, in an indoor setting. The current paper aims to evaluate volatile organic compound (VOC) emissions, particularly benzene, within indoor environments through the utilization of an experimental clean room. Experimental findings showed that 10 types of incense sticks emitted benzene in concentrations between 11.1 and 66.5 μg m−3, which were 2.5 lower than the limit suggested for non-occupation indoor exposure (160 μg m−3), identified by the American Association of Industrial Hygienists (ACGIH). Furthermore, a correlation between the dimensions (diameter and length) of the combustible parts in an incense stick was investigated and indicated a slight influence on the release of benzene. Taking into consideration the substantial influence benzene has on human health, coupled with a lack of precise legislation regarding indoor air quality in residential settings, this research serves as an initial investigation into the noteworthy effects of burning incense in private and public indoor settings.

The placenta is a crucial interface between the fetus and the maternal environment. It allows for nutrient absorption, thermal regulation, waste elimination, and gas exchange through the mother’s blood supply. Furthermore, the placenta determines important adjustments and epigenetic modifications that can change the phenotypic expression of the individual even long after birth. Polyethylene glycol (PEG) is a polyether compound derived from petroleum with many applications, from medicine to industrial manufacturing. In this study, for the first time, an integration of ultra-high-performance liquid chromatography (UHPLC) coupled with mass spectrometry (MS) was used to detect suites of PEG compounds in human placenta samples, collected from 12 placentas, originating from physiological pregnancy. In 10 placentas, we identified fragments of PEG in both chorioamniotic membranes and placental cotyledons, for a total of 36 samples.

In recent years, the use of hop extracts in industrial and home brewing processes as an alternative to hop cones or pellets usually added to wort during boiling has become increasingly popular. These extracts represent concentrated sources of bitter compounds, i.e., α- and β-acids, which are involved in some of the main reactions that take place in the wort and are responsible for the bitterness and the final quality of beer. This work aims at proposing a novel extraction technique, using a hydrofluorocarbon solvent in subcritical conditions; this process provided an extraction yield of 19% and an α-acid recovery of approximately 49% in 120 min of process. The α-acid isomerization kinetics of thermally treated hop extracts were studied and compared with those of both hop pellets and a CO2 extract. Laboratory scale tests showed that shorter boiling times were needed using hydrofluorocarbon and CO2 extracts (approximately 25 min and 34 min, respectively) to reach the same isomerization efficiency of 16.73%, achieved in 50 min of boiling with pellets. Moreover, the process was scaled up and the possibility of considerably reducing the conventional treatment times using hydrofluorocarbon extracts was confirmed: the same isomerization yield (9.1%) obtained after 50 min using the traditional procedure with hop pellets was reached in a shorter time of approximately 35 min in a pilot apparatus.

The peculiar properties of water are recalled, among them the “memory of water”, underlining the behavior of cell water, whose “ordered” structure is probably due to the endogenous electromagnetic fields generated by organelles inside the cells, such mitochondria and microtubules. Biological and clinical implications of water dynamic changes are reported, mainly based on SEP (Skin Electric Parameters) analysis and a hypothesis that has been advanced about an “action at distance” exerted by low concentration drugs. Nowadays, regarding measures of electro-cutaneous parameters our research can resort to a device of advanced electronics, APEC 300, that, beside an Electro Acupuncture operational function, but with quantitative precise values, can detect micro variations on parameters of cell aqueous solutions, and those of the water too, when the analyzed object is solicited by an external electromagnetic weak field, as well as by a drug at a very low concentration. A draft of two possible lines of research is outlined in conclusions, one depending only on ourselves and regarding “water tests” in the context of the “memory of water” experiments. By the side of EIS experiments about conductivity and impedance spectroscopy, in this article very high-resolution measures are suggested, by means of APEC 300, of an important parameter, the potential; a kind of measurements less complex and more reliable regarding the device/object interference, to which can besides easily be associated a frequency spectrum in the extremely low frequency region. In this line of research, it is the first time, for what we know, that some measurements of the potential, with its frequency spectrum, have been carried out for water without and with stimulation (the latter represented by the action of a magnetic field). This first set of measures by APEC 300 reveals the region 0–0.5 Hz as one of special interest.

Proton therapy represents a technologically advanced method for delivery of radiation treatments to tumors. The determination of the biological effectiveness is one of the objectives of the MoVe IT (Modeling and Verification for Ion Beam Treatment Planning) project of the National Institute for Nuclear Physics (INFN) CSN5. The aim of the present work, which is part of the project, was to evaluate the performance of the thermoluminescent dosimeters (TLDs-100) for dose verification in the proton beam line. Four irradiation experiments were performed in the experimental room at the Trento Proton Therapy Center, where a 150 MeV monoenergetic proton beam is available. A total of 80 TLDs were used. The TLDs were arranged in one or two rows and accommodated in a specially designed water-equivalent phantom. In the experimental setup, the beam enters orthogonally to the dosimeters and is distributed along the proton beam profile, while the irradiation delivers doses of 0.8 Gy or 1.5 Gy in the Bragg peak. For each irradiation stage, the depth–dose curve was determined by the TLD readings. The results showed the good performance of the TLDs-100, proving their reliability for dose recordings in future radiobiological experiments planned within the MoVe IT context.

In recent years, studies on climate change have focused on reducing greenhouse gas emissions emitted by various civil and industrial processes. This study highlights the importance of characterizing the total deposition rates of airborne particles (bulk atmospheric deposition) in the surroundings of an industrial area along the north cost of the Lazio Region in Italy, to deepen knowledge about the potential impact of emissions from the coal-fired thermoelectric (CTE) power plant and other possible sources existing in the surrounding area. Four sampling sites were identified, and the monitoring plan was performed a yearlong with monthly collecting observation. The deposition samples were collected monthly and processed for determining organic (polychlorinated dibenzo-para-dioxins, PCDDs; polychlorinated dibenzofurans, PCDFs; dioxin-like polychlorinated biphenyls, DL-PCBs; polycyclic aromatic hydrocarbons, PAHs) and inorganic (metals) substances. The samples were collected monthly and sent for chemical characterization. In Europe and Italy, no reference values have been given for the deposition rates of chemicals, while some European countries have determined reference/guide values to which the authors will refer in this study. Therefore, the analytical results show that the deposition rates for PCDD/Fs and DL-PCBs are lower with respects guide values defined by Germany and Belgium; PAHs values are in line with those measured in other rural-type sites, while for metals the analytical results show a situation between rural and urban area. The approach used in this study can help to identify reference values for Italy in deposition rates, with the aim both to characterize the dynamic of pollution in area with multiple risk factors and to describe and protect human health from environmental exposures caused by the contamination of the food chain.

Hair is an ideal tissue for tracing the human health conditions. It can be cut easily and painlessly, and the relative clinical results can give an indication of mineral status and toxic metal accumulation following long-term or even acute exposure. Different authors have found outdoor pollution phenomena, such as the levels, significantly alter metal and metalloid hair contents. This paper investigates the element concentration variability in hair samples collected from a not-exposed teenager, neither environmentally nor professionally. The sampling was carried out for one week, and the samples were collected from different locations on the scalp. A nuclear analytical methodology, i.e., the Instrumental Neutron Activation Analysis, is used for determining about 30 elements. Some differences have been found among the samplings as well as between the proximal and distal sections. A deep comparison with other similar studies worldwide present in the literature has been performed for evidencing the relationships and the differences due to different ethnical origins, lifestyles, diets, and climates among the different young populations.

The transcription factor Forkhead box E1 (FOXE1) is a key player in thyroid development and function and has been identified by genome-wide association studies as a susceptibility gene for papillary thyroid cancer. Several cancer-associated polymorphisms fall into gene regulatory regions and are likely to affect FOXE1 expression levels. However, the possibility that changes in FOXE1 expression modulate thyroid cancer development has not been investigated. Here, we describe the effects of FOXE1 gene dosage reduction on cancer phenotype in vivo. Mice heterozygous for FOXE1 null allele (FOXE1+/−) were crossed with a BRAFV600E-inducible cancer model to develop thyroid cancer in either a FOXE1+/+ or FOXE1+/− genetic background. In FOXE1+/+ mice, cancer histological features are quite similar to that of human high-grade papillary thyroid carcinomas, while cancers developed with reduced FOXE1 gene dosage maintain morphological features resembling less malignant thyroid cancers, showing reduced proliferation index and increased apoptosis as well. Such cancers, however, appear severely undifferentiated, indicating that FOXE1 levels affect thyroid differentiation during neoplastic transformation. These results show that FOXE1 dosage exerts pleiotropic effects on thyroid cancer phenotype by affecting histology and regulating key markers of tumor differentiation and progression, thus suggesting the possibility that FOXE1 could behave as lineage-specific oncogene in follicular cell-derived thyroid cancer.

Cell plasticity is the ability that cells have to modify their phenotype, adapting to the environment. Cancer progression is under the strict control of the the tumor microenvironment that strongly determines its success by regulating the behavioral changes of tumor cells. The cross-talk between cancer and stromal cells and the interactions with the extracellular matrix, hypoxia and acidosis contribute to trigger a new tumor cell identity and to enhance tumor heterogeneity and metastatic spread. In highly aggressive triple-negative breast cancer, tumor cells show a significant capability to change their phenotype under the pressure of the hypoxic microenvironment. In this study, we investigated whether targeting the hypoxia-induced protein carbonic anhydrase IX (CA IX) could reduce triple-negative breast cancer (TNBC) cell phenotypic switching involved in processes associated with poor prognosis such as vascular mimicry (VM) and cancer stem cells (CSCs). The treatment of two TNBC cell lines (BT-549 and MDA-MB-231) with a specific CA IX siRNA or with a novel inhibitor of carbonic anhydrases (RC44) severely impaired their ability to form a vascular-like network and mammospheres and reduced their metastatic potential. In addition, the RC44 inhibitor was able to hamper the signal pathways involved in triggering VM and CSC formation. These results demonstrate that targeting hypoxia-induced cell plasticity through CA IX inhibition could be a new opportunity to selectively reduce VM and CSCs, thus improving the efficiency of existing therapies in TNBC.

A low solvent consumption method for the determination of non-steroidal anti-inflammatory drugs (NSAIDs) in animal urine samples is studied. The NSAIDs were extracted with CH2Cl2 by the ultrasound vortex assisted dispersive liquid–liquid microextraction (USVA-DLLME) method from urine samples, previously treated with β-glucuronidase/acrylsulfatase. After centrifugation, the bottom phase of the chlorinated solvent was separated from the liquid matrix, dried with Na2SO4, and derivatized with N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) + trimethylchlorosilane (TMCS) (99 + 1). After cooling at room temperature, the solution was concentrated under nitrogen flow, and 1 µL of solution was analyzed in gas chromatography/ion trap-mass spectrometry (GC-IT-MS). The enrichment factor was about 300–450 times and recoveries ranged from 94.1 to 101.2% with a relative standard deviation (RSD) of ≤4.1%. The USVA-DLLME process efficiency was not influenced by the characteristics of the real urine matrix; therefore, the analytical method characteristics were evaluated in the range 1–100 ng mL−1 (R2 ≥ 0.9950). The limits of detection (LODs) and limits of quantification (LOQs) were between 0.1 and 0.2 ng mL−1 with RSD ≤4.5% and between 4.1 and 4.7 ng mL−1 with RSD ≤3.5%, respectively, whereas inter- and intra-day precision was 3.8% and 4.5%, respectively. The proposed analytical method is reproducible, sensitive, and simple.

Solid–liquid separation is a key unit operation in the wastewater treatment, generally consisting of coagulation and flocculation steps to promote aggregation and increase the particle size, followed by sedimentation, where the particles settle due to the effect of gravity. The sedimentation efficiency is related to the hydrodynamic behavior of the suspended particles that, in turn, depends on the aggregate morphology. In addition, the non-Newtonian rheology of sludges strongly affects the drag coefficient of the suspended particles, leading to deviations from the known settling behavior in Newtonian fluids. In this work, we use direct numerical simulations to study the hydrodynamic drag of fractal-shaped particles suspended in a shear-thinning fluid modeled by the power-law constitutive equation. The fluid dynamics governing equations are solved for an applied force with different orientations uniformly distributed over the unit sphere. The resulting particle velocities are interpolated to compute the aggregate dynamics and the drag correction coefficient. A remarkable effect of the detailed microstructure of the aggregate on the sedimentation process is observed. The orientational dynamics shows a rich behavior characterized by steady-state, bistable, and periodic regimes. In qualitative agreement with spherical particles, shear-thinning increases the drag correction coefficient. Elongated aggregates sediment more slowly than sphere-like particles, with a lower terminal velocity as the aspect ratio increases.

Atmospheric pollution is an important task in life sciences and, in particular, inorganic fraction characterization is considered as an important issue in this field. For many years, researchers have focused their attention on the particulate matter fraction below 10 μm: in this case, our attention was also focused on PM2.5 (i.e., particles with a size fraction smaller than 2.5 μm) and PM1 (below 1 μm). This paper would like to investigate whether the element accumulation in different granulometric fractions is similar, or whether there are behavior dissimilarities. Among the different analytical techniques, the instrumental neutron activation analysis, an instrumental nuclear method, was used for its peculiarity of investigating the sample without performing any chemical-physical treatment. Forty-two daily samples using the reference method were collected, 15 filters for PM10, 18 for PM2.5, and 12 for PM1; the filters, along with primary standards and appropriate standard reference materials, were irradiated at the National Agency for New Technologies, Energy and Sustainable Economic Development (ENEA) R.C.-Casaccia’s Triga MARK II reactor. The irradiations carried out in the Rabbit and Lazy Susan channels allowed for the investigation of 36 elements and the relative Pearson’s correlations between elements and PM-fractions (PM10 vs. PM2.5 was good, whereas PM10 vs. PM1 was the worst). The Enrichment Factors were studied for the three fractions to show how anthropogenic sources have affected the element content. A comparison between these data and element levels determined worldwide showed that our concentrations were lower than those determined in similar scenarios. Furthermore, a statistical approach (source discrimination, hierarchical cluster analysis, principal component analysis) has allowed us to identify similarities between the samples: the airborne filters can be divided in two main groups (i.e., one made of PM10 and PM2.5 filters and one only of PM1 filters), meaning a different element contribution to this fraction coming from other sources present at the site.

In this paper, an analytical protocol was developed for the simultaneous determination of phthalates (di-methyl phthalate DMP, di-ethyl phthalate DEP, di-isobutyl phthalate DiBP, di-n-butyl phthalate DBP, bis-(2-ethylhexyl) phthalate DEHP, di-n-octyl phthalate DNOP) and bisphenol A (BPA). The extraction technique used was the ultrasound vortex assisted dispersive liquid−liquid microextraction (UVA-DLLME). The method involves analyte extraction using 75 µL of benzene and subsequent analysis by gas chromatography combined with ion trap mass spectrometry (GC-IT/MS). The method is sensitive, reliable, and reproducible with a limit of detection (LOD) below 13 ng g−1 and limit of quantification (LOQ) below 22 ng g−1 and the intra- and inter-day errors below 7.2 and 9.3, respectively. The method developed and validated was applied to six honey samples (i.e., four single-use commercial ones and two home-made ones. Some phthalates were found in the samples at concentrations below the specific migration limits (SMLs). Furthermore, the commercial samples were subjected to two different thermal stresses (24 h and 48 h at 40 °C) for evidence of the release of plastic from the containers. An increase in the phthalate concentrations was observed, especially during the first phase of the shock, but the levels were still within the limits of the regulations.

Phthalates (or phthalate esters, PAEs) and bisphenol A (BPA) are widely used in various industries, particularly in the fields of cosmetics and packaging, and they increase the malleability and workability of materials. As a result of their use, some international health organizations have begun to study them. In this study, the authors developed a methodology for the simultaneous determination of dimethyl phthalate (DMP), diethyl phthalate (DEP), diisobutyl phthalate (DiBP); dibutyl phthalate (DBP), bis(2-ethylhexyl) phthalate (DEHP); di-n-octyl-phthalate (DnOP) and bisphenol A (BPA) from drinking and non-potable waters. The extraction of PAEs and BPA was performed using a solvent-based dispersive liquid−liquid microextraction (SB-DLLME) method. The analytical determination was performed using a gas chromatography−ion trap mass spectrometry (GC-IT/MS) analysis. The entire procedure was validated as recoveries were studied according to the volume and the extraction solvent used, pH, and ionic strength. Dynamic linearity ranges and linear equations of all the compounds were experimentally determined as well as the limit of detection (LOD) (1−8 ng mL−1) and the limit of quantification (LOQ) (5−14 ng mL−1), reproducibility, and sensitivity. The method was applied to 15 water samples (mineral water and tap water) for determining PAEs and BPA released from the plastic container. After the release simulation, four PAEs (i.e., DiBP, DBP, DHEP, and DnOP) were determined at very low concentrations (below 1.2 ng mL−1) in two water samples from (sport) bottles.

Cytokinesis culminates in the final separation, or abscission, of the two daughter cells at the end of cell division. Abscission relies on an organelle, the midbody, which forms at the intercellular bridge and is composed of various proteins arranged in a precise stereotypic pattern. The molecular mechanisms controlling midbody organization and function, however, are obscure. Here we show that proper midbody architecture requires cross-regulation between two cell division kinases, Citron kinase (CIT-K) and Aurora B, the kinase component of the chromosomal passenger complex (CPC). CIT-K interacts directly with three CPC components and is required for proper midbody architecture and the orderly arrangement of midbody proteins, including the CPC. In addition, we show that CIT-K promotes Aurora B activity through phosphorylation of the INCENP CPC subunit at the TSS motif. In turn, Aurora B controls CIT-K localization and association with its central spindle partners through phosphorylation of CIT-K's coiled coil domain. Our results identify, for the first time, a cross-regulatory mechanism between two kinases during cytokinesis, which is crucial for establishing the stereotyped organization of midbody proteins.

The chromosomal passenger complex (CPC)—composed of Aurora B kinase, Borealin, Survivin and INCENP—surveys the fidelity of genome segregation throughout cell division. The CPC has been proposed to prevent polyploidy by controlling the final separation (known as abscission) of the two daughter cells via regulation of the ESCRT-III CHMP4C component. The molecular details are, however, still unclear. Using atomic force microscopy, we show that CHMP4C binds to and remodels membranes in vitro. Borealin prevents the association of CHMP4C with membranes, whereas Aurora B interferes with CHMP4C's membrane remodelling activity. Moreover, we show that CHMP4C phosphorylation is not required for its assembly into spiral filaments at the abscission site and that two distinctly localized pools of phosphorylated CHMP4C exist during cytokinesis. We also characterized the CHMP4C interactome in telophase cells and show that the centralspindlin complex associates preferentially with unphosphorylated CHMP4C in cytokinesis. Our findings indicate that gradual dephosphorylation of CHMP4C triggers a ‘relay’ mechanism between the CPC and centralspindlin that regulates the timely distribution and activation of CHMP4C for the execution of abscission.

Background: Somatotropic axis dysfunction associated with non-alcoholic fatty liver disease (NAFLD) has potential multisystemic detrimental effects. Here, we analysed the effects of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) supplementation on liver histology, adipokine profile and muscle function in an NAFLD model. Methods: C57BL/6 mice were fed with a high fat diet (HFD) for 12 weeks and were separated into three groups treated for 4 weeks with: (1) High fat diet (HFD) (n = 10); (2) HFD + GH 9 μg/g/d (n = 10); (3) HFD + IGF-1 0.02 µg/g/d (n = 9). A control group fed a chow diet was included (n = 6). Liver histology, liver triglycerides content, serum alanine aminotransferase (ALT) activity, adiponectin and leptin serum levels, in vivo muscle strength, tetanic force and muscle fibre cross-sectional area (CSA) were measured. Results: HFD + GH and HFD + IGF-1 groups showed significantly lower ALT activity compared to HFD (p < 0.01). Liver triglyceride content in HFD + GH was decreased compared to HFD (p < 0.01). Histologic steatosis score was increased in HFD and HFD + GH group (p < 0.01), whereas HFD + IGF-1 presented no difference compared to the chow group (p = 0.3). HFD + GH group presented lower serum leptin and adiponectin levels compared to HFD. GH and IGF-1 supplementation therapy reverted HFD-induced reduction in muscle strength and CSA (sarcopenia). Conclusions: GH and IGF-1 supplementation induced significant improvement in liver steatosis, aminotransferases and sarcopenia in a diet-induced NAFLD model.

Tumor angiogenesis is widely recognized as one of the “hallmarks of cancer”. Consequently, during the last decades the development and testing of commercial angiogenic inhibitors has been a central focus for both basic and clinical cancer research. While antiangiogenic drugs are now incorporated into standard clinical practice, as with all cancer therapies, tumors can eventually become resistant by employing a variety of strategies to receive nutrients and oxygen in the event of therapeutic assault. Herein, we concentrate and review in detail three of the principal mechanisms of antiangiogenic therapy escape: (1) upregulation of compensatory/alternative pathways for angiogenesis; (2) vasculogenic mimicry; and (3) vessel co-option. We suggest that an understanding of how a cancer cell adapts to antiangiogenic therapy may also parallel the mechanisms employed in the bourgeoning tumor and isolated metastatic cells delivering responsible for residual disease. Finally, we speculate on strategies to adapt antiangiogenic therapy for future clinical uses.

Summary Cytokinesis controls the proper segregation of nuclear and cytoplasmic materials at the end of cell division. The chromosomal passenger complex (CPC) has been proposed to monitor the final separation of the two daughter cells at the end of cytokinesis in order to prevent cell abscission in the presence of DNA at the cleavage site, but the precise molecular basis for this is unclear. Recent studies indicate that abscission could be mediated by the assembly of filaments comprising components of the endosomal sorting complex required for transport-III (ESCRT-III). Here, we show that the CPC subunit Borealin interacts directly with the Snf7 components of ESCRT-III in both Drosophila and human cells. Moreover, we find that the CPC's catalytic subunit, Aurora B kinase, phosphorylates one of the three human Snf7 paralogues—CHMP4C—in its C-terminal tail, a region known to regulate its ability to form polymers and associate with membranes. Phosphorylation at these sites appears essential for CHMP4C function because their mutation leads to cytokinesis defects. We propose that CPC controls abscission timing through inhibition of ESCRT-III Snf7 polymerization and membrane association using two concurrent mechanisms: interaction of its Borealin component with Snf7 proteins and phosphorylation of CHMP4C by Aurora B.

Oomycetes represent some of the most devastating plant and animal pathogens. Typical examples are Phytophthora infestans, which causes potato and tomato late blight, and Saprolegnia parasitica, responsible for fish diseases. Despite the economical and environmental importance of oomycete diseases, their control is difficult, particularly in the aquaculture industry. Carbohydrate synthases are vital for hyphal growth and represent interesting targets for tackling the pathogens. The existence of 2 different chitin synthase genes (SmChs1 and SmChs2) in Saprolegnia monoica was demonstrated using bioinformatics and molecular biology approaches. The function of SmCHS2 was unequivocally demonstrated by showing its catalytic activity in vitro after expression in Pichia pastoris. The recombinant SmCHS1 protein did not exhibit any activity in vitro, suggesting that it requires other partners or effectors to be active, or that it is involved in a different process than chitin biosynthesis. Both proteins contained N-terminal Microtubule Interacting and Trafficking domains, which have never been reported in any other known carbohydrate synthases. These domains are involved in protein recycling by endocytosis. Enzyme kinetics revealed that Saprolegnia chitin synthases are competitively inhibited by nikkomycin Z and quantitative PCR showed that their expression is higher in presence of the inhibitor. The use of nikkomycin Z combined with microscopy showed that chitin synthases are active essentially at the hyphal tips, which burst in the presence of the inhibitor, leading to cell death. S. parasitica was more sensitive to nikkomycin Z than S. monoica. In conclusion, chitin synthases with species-specific characteristics are involved in tip growth in Saprolegnia species and chitin is vital for the micro-organisms despite its very low abundance in the cell walls. Chitin is most likely synthesized transiently at the apex of the cells before cellulose, the major cell wall component in oomycetes. Our results provide important fundamental information on cell wall biogenesis in economically important species, and demonstrate the potential of targeting oomycete chitin synthases for disease control.