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Natural products are thoroughly studied as valuable alternatives to synthetic insecticides. Heracleum persicum Desf. ex Fisch. (Apiaceae), commonly known as Golpar, is an Iranian medicinal plant largely employed as a spice, which has previously revealed insecticidal potential. The chemical composition of H. persicum essential oil (EO) was investigated by GC-MS and was mainly dominated by hexyl butyrate (36.1%) and octyl acetate (23.7%). The EO and its main esters were tested on three mosquito species. Aedes aegypti (L.) larvae were the most sensitive to all tested products. Lethal concentrations (LC50) of 59.09, 53.59, and 47.05 ppm were recorded for the EO, hexyl butyrate, and octyl acetate, respectively. Aedes albopictus (Skuse) and Anopheles gambiae Giles demonstrated comparable sensitivity to the EO, with LC50 values of 102.97 and 97.91 ppm, respectively, whereas the isolated constituents appeared more active on An. gambiae (LC50 of hexyl butyrate and octyl acetate of 70.97 and 60.71 ppm, respectively) with respect to Ae. albopictus (LC50 of hexyl butyrate and octyl acetate of 85.40 and 91.38 ppm, respectively). Low toxicity was registered for both EO and single components against human embryonic kidney (HEK293) cells. Overall, the H. persicum EO, hexyl butyrate, and octyl acetate could be further considered for larvicide development. [ABSTRACT FROM AUTHOR]

Microbial activity has been documented in various lacustrine environments, suggesting its fundamental role in mineral precipitation and, therefore, in the formation of organo-deposits such as microbialites. Many studies are currently focused on documenting how the association of microbes and extracellular polymeric substances (EPSs) may influence the authigenesis of Mg-rich clay minerals and the subsequent carbonate precipitation in growing microbialites in lacustrine environments. In this study, we investigate the present-day microbialites of the alkaline Bagno dell'Acqua lake (Pantelleria Island, Italy) using X-ray diffraction (XRD) scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS). Our results reveal the intimate association of Mg-smectite/carbonate minerals with the EPS and microbes, and, for the first time, we selected microbes belonging to phylum Firmicutes (Bacillus sp.), from natural microbialites, to carry out laboratory experiments that testify their direct role in the precipitation of clay and carbonate minerals. [ABSTRACT FROM AUTHOR]

Organogenesis occurs in the uterus under low oxygen levels (4%). Preterm birth exposes immature newborns to a hyperoxic environment, which can induce a massive production of reactive oxygen species and potentially affect organ development, leading to diseases such as necrotizing enterocolitis. The β3-adrenoreceptor (β3-AR) has an oxygen-dependent regulatory mechanism, and its activation exerts an antioxidant effect. To test the hypothesis that β3-AR could protect postnatal ileal development from the negative impact of high oxygen levels, Sprague–Dawley rat pups were raised under normoxia (21%) or hyperoxia (85%) for the first 2 weeks after birth and treated or not with BRL37344, a selective β3-AR agonist, at 1, 3, or 6 mg/kg. Hyperoxia alters ileal mucosal morphology, leading to increased cell lipid oxidation byproducts, reduced presence of β3-AR-positive resident cells, decreased junctional protein expression, disrupted brush border, mucin over-production, and impaired vascularization. Treatment with 3 mg/kg of BRL37344 prevented these alterations, although not completely, while the lower 1 mg/kg dose was ineffective, and the higher 6 mg/kg dose was toxic. Our findings indicate the potential of β3-AR agonism as a new therapeutic approach to counteract the hyperoxia-induced ileal alterations and, more generally, the disorders of prematurity related to supra-physiologic oxygen exposure. [ABSTRACT FROM AUTHOR]

Oxygen level is a key regulator of organogenesis and its modification in postnatal life alters the maturation process of organs, including the intestine, which do not completely develop in utero. The β3-adrenoreceptor (β3-AR) is expressed in the colon and has an oxygen-dependent regulatory mechanism. This study shows the effects of the β3-AR agonist BRL37344 in a neonatal model of hyperoxia-driven colonic injury. For the first 14 days after birth, Sprague–Dawley rat pups were exposed to ambient oxygen levels (21%) or hyperoxia (85%) and treated daily with BRL37344 at 1, 3, 6 mg/kg or untreated. At the end of day 14, proximal colon samples were collected for analysis. Hyperoxia deeply influences the proximal colon development by reducing β3-AR-expressing cells (27%), colonic length (26%) and mucin production (47%), and altering the neuronal chemical coding in the myenteric plexus without changes in the neuron number. The administration of BRL37344 at 3 mg/kg, but not at 1 mg/kg, significantly prevented these alterations. Conversely, it was ineffective in preventing hyperoxia-induced body weight loss. BRL37344 at 6 mg/kg was toxic. These findings pave the way for β3-AR pharmacological targeting as a therapeutic option for diseases caused by hyperoxia-impaired development, typical prematurity disorders. [ABSTRACT FROM AUTHOR]

Unmet needs remain in later lines chronic myeloid leukemia (CML): the response rate and the overall survival of resistant patients in the chronic phase who changed a second-generation TKI in the second line with another TKI with similar action are usually poor, while the off-target toxicities and the potential development of mutations increase. The recent approval of asciminib, a STAMP inhibitor, in the third line, has the potential to soon change the therapeutic algorithm for this subset of patients. Here, we report the results of a GIMEMA survey assessing the number of patients currently treated in the third line in Italy, the current approach in later lines by Italian physicians, and the future role of this drug according to the reason to switch to asciminib (resistance and/or intolerance), as well as the perceptions about the future position of this agent. [ABSTRACT FROM AUTHOR]

Microalgae and cyanobacteria are diverse groups of organisms with great potential to benefit societies across the world. These organisms are currently used in food, feed, pharmaceutical and cosmetic industries. In addition, a variety of novel compounds are being isolated. Commercial production of photosynthetic microalgae and cyanobacteria requires cultivation on a large scale with high throughput. However, scaling up production from lab-based systems to large-scale systems is a complex and potentially costly endeavor. In this review, we summarise all aspects of large-scale cultivation, including aims of cultivation, species selection, types of cultivation (ponds, photobioreactors, and biofilms), water and nutrient sources, temperature, light and mixing, monitoring, contamination, harvesting strategies, and potential environmental risks. Importantly, we also present practical recommendations and discuss challenges of profitable large-scale systems associated with economical design, effective operation and maintenance, automation, and shortage of experienced phycologists. [ABSTRACT FROM AUTHOR]

The increasing interest in stretchable conductive composite materials, that can be versatile and suitable for wide-ranging application, has sparked a growing demand for studies of scalable fabrication techniques and specifically tailored geometries. Thanks to the combination of the conductivity and robustness of carbon nanotube (CNT) materials with the viscoelastic properties of polymer films, in particular their stretchability, "surface composites" made of a CNT on polymeric films are a promising way to obtain a low-cost, conductive, elastic, moldable, and patternable material. The use of polymers selected for specific applications, however, requires targeted studies to deeply understand the interface interactions between a CNT and the surface of such polymer films, and in particular the stability and durability of a CNT grafting onto the polymer itself. Here, we present an investigation of the interface properties for a selected group of polymer film substrates with different viscoelastic properties by means of a series of different and complementary experimental techniques. Specifically, we studied the interaction of a single-wall carbon nanotube (SWCNT) deposited on two couples of different polymeric substrates, each one chosen as representative of thermoplastic polymers (i.e., low-density polyethylene (LDPE) and polypropylene (PP)) and thermosetting elastomers (i.e., polyisoprene (PI) and polydimethylsiloxane (PDMS)), respectively. Our results demonstrate that the characteristics of the interface significantly differ for the two classes of polymers with a deeper penetration (up to about 100 μm) into the polymer bulk for the thermosetting substrates. Consequently, the resistance per unit length varies in different ranges, from 1–10 kΩ/cm for typical thermoplastic composite devices (30 μm thick and 2 mm wide) to 0.5–3 MΩ/cm for typical thermosetting elastomer devices (150 μm thick and 2 mm wide). For these reasons, the composites show the different mechanical and electrical responses, therefore suggesting different areas of application of the devices based on such materials. [ABSTRACT FROM AUTHOR]

The development of coatings for accident-tolerant fuels (ATFs) for light water reactor (LWR) applications promises improved corrosion resistance under accident conditions and better performances during operation. CrN and TiN coatings are characterized by high wear resistance coupled with good corrosion resistance properties. They are generally used to protect materials in applications where extreme conditions are involved and represent promising candidates for ATF. Zr cladding tubes coated with 5 µm-thick CrN or TiN, exposed in an autoclave to simulated PWR chemistry and BWR chemistry, were characterized with SEM, EDS, and STEM. The investigation focused on the performance and oxidation mechanisms of the coated claddings under simulated reactor chemistry. Both coatings provided improved oxidation resistance in a simulated PWR environment, where passivating films of Cr2O3 and TiO2, less than 1 µm-thick, formed on the CrN and TiN outer surfaces, respectively. Under the more challenging BWR conditions, any formed Cr2O3 dissolved into the oxidizing water, resulting in the complete dissolution of the CrN coating. For the TiN coating, the formation of a stable TiO2 film was observed under BWR conditions, but the developed oxide film was unable to stop the flux of oxygen to the substrate, causing the oxidation of the substrate. [ABSTRACT FROM AUTHOR]

Assessing the influence of landscape pattern changes on ecosystem service value (ESV) is critical for developing land-use polies and increasing ecosystem services. The data sources include remote-sensing image data and statistical yearbooks from 2000, 2010, and 2020. This study employs the patch-generating land-use simulation model, landscape pattern index, and ecological service value estimation to analyse the changes in landscape patterns and ESV in Fujian coastal areas over the last 20 years. The landscape pattern and ESV in the future (2050) are then simulated under the low-carbon scenario (LCS), with the natural development scenario (NDS) serving as a comparison. The results show that: (1) the most noticeable changes from 2000 to 2020 are the reduced cultivated land area and the rapid expansion of construction land area. By 2050, construction land will account for 7.67% of the total land area under LCS, whereas NDS will account for 9.45%, and changes in the landscape pattern indices all indicate there will be greater variety and fragmentation of the landscape, with the NDS being more serious than the LCS; (2) From 2000–2020, the total ESV value showed a decreasing trend. In 2050, the ESV under the LCS will be 122.387 billion yuan, which is higher than the 121.434 billion yuan under the NDS. Regulating services contribute the most to the total ESV, followed by support services; and (3) In the past 20 years, except for a slight increase in water area, the ESV of other landscapes has decreased, with a net decrease of 3.134 billion yuan in total. The R2 fitting between the area change of cultivated and construction land and the total ESV reached 0.9898 and 0.9843, respectively. The correlations between ESV and landscape indices indicate that landscape pattern changes significantly impact ESV. Simulating ESV in LCS can provide guidance for optimising landscape patterns, promoting the benign operation of the regional ecosystem, and achieving sustainable ecological development. [ABSTRACT FROM AUTHOR]

Gliomas are the most common primary malignant brain tumors. Glioblastoma, IDH-wildtype (GBM, CNS WHO grade 4) is the most aggressive form of glioma and is characterized by extensive hypoxic areas that strongly correlate with tumor malignancy. Hypoxia promotes several processes, including stemness, migration, invasion, angiogenesis, and radio- and chemoresistance, that have direct impacts on treatment failure. Thus, there is still an increasing need to identify novel targets to limit GBM relapse. Polysialic acid (PSA) is a carbohydrate composed of a linear polymer of α2,8-linked sialic acids, primarily attached to the Neural Cell Adhesion Molecule (NCAM). It is considered an oncodevelopmental antigen that is re-expressed in various tumors. High levels of PSA-NCAM are associated with high-grade and poorly differentiated tumors. Here, we investigated the effect of PSA inhibition in GBM cells under low oxygen concentrations. Our main results highlight the way in which hypoxia stimulates polysialylation in U87-MG cells and in a GBM primary culture. By lowering PSA levels with the sialic acid analog, F-NANA, we also inhibited GBM cell migration and interfered with their differentiation influenced by the hypoxic microenvironment. Our findings suggest that PSA may represent a possible molecular target for the development of alternative pharmacological strategies to manage a devastating tumor like GBM. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AML) is a hematological malignancy originating from defective hematopoietic stem cells in the bone marrow. In spite of the recent approval of several molecular targeted therapies for AML treatment, disease recurrence remains an issue. Interestingly, increasing evidence has pointed out the relevance of bone marrow (BM) niche remodeling during leukemia onset and progression. Complex crosstalk between AML cells and microenvironment components shapes the leukemic BM niche, consequently affecting therapy responsiveness. Notably, circular RNAs are a new class of RNAs found to be relevant in AML progression and chemoresistance. In this review, we provided an overview of AML-driven niche remodeling. In particular, we analyzed the role of circRNAs and their possible contribution to cell–cell communication within the leukemic BM microenvironment. Understanding these mechanisms will help develop a more effective treatment for AML. [ABSTRACT FROM AUTHOR]

This paper addresses the problem of interactive auralization of enclosures based on a finite superposition of plane waves. For this, room acoustic simulations are performed using the Finite Element (FE) method. From the FE solution, a virtual microphone array is created and an inverse method is implemented to estimate the complex amplitudes of the plane waves. The effects of Tikhonov regularization are also considered in the formulation of the inverse problem, which leads to a more efficient solution in terms of the energy used to reconstruct the acoustic field. Based on this sound field representation, translation and rotation operators are derived enabling the listener to move within the enclosure and listen to the changes in the acoustic field. An implementation of an auralization system based on the proposed methodology is presented. The results suggest that the plane wave expansion is a suitable approach to synthesize sound fields. Its advantage lies in the possibility that it offers to implement several sound reproduction techniques for auralization applications. Furthermore, features such as translation and rotation of the acoustic field make it convenient for interactive acoustic renderings. [ABSTRACT FROM AUTHOR]

A key challenge for the improvement of clear cell renal cell carcinoma (ccRCC) management could derive from a deeper characterization of the biology of these neoplasms that could greatly improve the diagnosis, prognosis and treatment choice. The aim of this study was to identify specific miRNAs that are deregulated in tumor vs. normal kidney tissues and that could impact on the biology of ccRCC. To this end we selected four miRNAs (miR-21-5p, miR-210-3p, miR-185-5p and miR-221-3p) and their expression has been evaluated in a retrospective cohort of formalin-fixed paraffin-embedded (FFPE) tissues from 20 ccRCC patients who underwent surgical nephrectomy resection. miR-21-5p and miR-210-3p resulted the most significantly up-regulated miRNAs in this patient cohort, highlighting these onco-miRNAs as possible relevant players involved in ccRCC tumorigenesis. Thus, this study reports the identification of specific oncogenic miRNAs that are altered in ccRCC tissues and suggests that they might be useful biomarkers in ccRCC management. [ABSTRACT FROM AUTHOR]

The coordinated expression and interplay among lineage specific transcription factors and microRNAs contribute to the regulation of gene expression and determination of cell specificity. In hematopoietic stem cells (HSCs), unique combinations of transcription factors largely control growth and maturation of different blood cell lineages through cooperative regulation of specific target genes. MicroRNAs provide an additional level of control beyond transcription factors. By acting as regulators of crucial lineage-specific genetic programs, microRNAs direct early multipotential progenitor cells to adopt a certain cell fate program. Thus, alteration of specific microRNA levels may affect proliferation, differentiation and genetic stability of HSCs, contributing to the onset of myeloproliferative disorders and leukemia. The major aim of this review is to highlight the critical role of microRNA-regulated pathways during the establishment and progression of hematological malignancies, with a particular attention to leukemia, lymphomas and myelodysplastic syndromes. This will give us the opportunity to discuss the potential use of microRNA-based therapeutic approaches in these diseases. MicroRNAs are indeed emerging as relevant tools to improve the efficacy of currently used therapeutic protocols. [ABSTRACT FROM AUTHOR]

Non-coding RNAs (ncRNAs) play a pivotal role in regulating the tumor microenvironment (TME) by controlling gene expression at multiple levels. In tumors, ncRNAs can mediate the crosstalk between cancer cells and other cells in the TME, such as immune cells, stromal cells, and endothelial cells, influencing tumor development and progression. Tumor-associated macrophages (TAMs) are among the most abundant inflammatory cells infiltrating solid cancers that promote tumorigenesis, and their infiltration correlates with a poor prognosis in many tumors. Cancer cells produce different ncRNAs that orchestrate TAM recruitment and polarization toward a tumor-promoting phenotype. Tumor-reprogrammed macrophages shape the TME by promoting angiogenesis and tissue remodeling, and suppressing the anti-tumor activity of adaptive immune cells. TAMs can also produce ncRNA molecules that boost cancer cell proliferation and direct their phenotype and metabolic changes facilitating cancer progression and metastasis. This review will focus on the crosstalk between cancer cells and TAMs mediated by microRNAs and long non-coding RNAs during breast cancer (BC) initiation and progression. [ABSTRACT FROM AUTHOR]

This work presents a novel type of actuator that improves over the standard cantilever by permitting daisy-chaining while minimising stress to the joint connecting to the load. A detailed structural and functional comparison of the proposed device against the cantilever actuator as a baseline is given, led by a brief revision of the cantilever actuator as the state-of-the-art that highlights its limitations with respect to daisy-chaining and the stress it inherently creates within the joint connecting to the load when attempting out-of-plane displacement without rotation. Simulations of both devices' performance confirm that the newly proposed device yields the targeted displacement profile that both enables the daisy-chaining of such a device into a higher-order actuator for increased displacement and reduce stress in the joint with the load. This comes at the cost of reduced maximum displacement compared to the cantilever, which can be overcome by daisy-chaining. The proposed device's performance is further evaluated on the basis of manufactured prototypes measured by means of a laser scanning vibrometer. The prototype was manufactured on a 150 μ m alumina substrate, and both electrodes and piezoelectric layer were deposited in a thick-film printing process. [ABSTRACT FROM AUTHOR]

Background and Aim: Diarrhea, abdominal pain, and bloating are frequent in irritable bowel syndrome (IBS)-like disorders, although little is known about their intestinal ultrastructural alterations. The aim of the present study was to study duodenal biopsies from IBS-like patients to find ultrastructural alterations. Materials and Methods: Study design: descriptive comparative pilot study. Thirty outpatients (9 male and 21 female; median age 37.7 years; range, 20 to 65 years) complaining of IBS-like symptoms were enrolled between January 2015 to May 2019 and were divided into 6 groups, each equally consisting of 5 patients: (A) untreated celiac disease (uCD); (B) treated celiac disease (tCD); (C) wheat allergy (WA); (D) Non-celiac gluten sensitivity (NCGS); (E) Nickel allergic contact mucositis (Ni ACM); (F) controls affected by GERD. Transmission electron microscopy (TEM) morphological characteristics were: microvilli length, intermicrovillar distance, junctional complexes (JC) gap width, autophagic bodies, apoptosis, altered mitochondria, lipid/chylomicron droplets, and mast cells. Regarding JC, we focused on tight junctions (TJ), adherens junctions (AJ), and desmosomes. Results: Major alterations in microvilli length and intermicrovillar distance have been observed in the subjects affected by uCD. Microvilli of tCD patients showed marked recovery after adequate GFD, although not comparable to controls. Intermediate microvillar alterations were instead observed in NCGS and Ni ACM, while characteristics of WA subjects appeared more similar to tCD. Regarding JC, TJ did not show significant differences between all groups studied, including controls. The AJ were significantly more dilated in all groups compared to controls, while no significant differences were found between the pathological groups. The distance between desmosomes was greater in uCD, NCGS, and Ni ACM than in tCD, WA, and controls. Finally, intracellular alterations have been detected in most of the groups studied although they seemed more unspecific. Conclusions: TEM analysis confirmed damages to the intestinal barrier and defense mechanisms by enterocytes in IBS-like patients, probably linked to low-grade inflammation or adverse reactions triggered by food allergens, heavy metals, or other unknown. On the other hand, our study needs confirmation and further investigations with larger populations to facilitate diagnosis, therapy, and prevention of IBS-like disorders in the future. [ABSTRACT FROM AUTHOR]

microRNAs (miRNAs) are emerging as relevant molecules in cancer development and progression. MiRNAs add a post-transcriptional level of control to the regulation of gene expression. The deregulation of miRNA expression results in changing the molecular circuitry in which miRNAs are involved, leading to alterations of cell fate determination. In this review, we describe the miRNAs that are emerging as innovative molecular biomarkers from liquid biopsies, not only for diagnosis, but also for post-surgery management in cancer. We focus our attention on renal cell carcinoma, in particular highlighting the crucial role of circulating miRNAs in clear cell renal cell carcinoma (ccRCC) management. In addition, the functional deregulation of miRNA expression in ccRCC is also discussed, to underline the contribution of miRNAs to ccRCC development and progression, which may be relevant for the identification and design of innovative clinical strategies against this tumor. [ABSTRACT FROM AUTHOR]

Growth and maturation of hematopoietic stem cells (HSCs) are largely controlled at both transcriptional and post-transcriptional levels. In particular, hematopoietic development requires a tight control of protein synthesis. Furthermore, translational deregulation strongly contributes to hematopoietic malignancies. Researchers have recently identified a new layer of gene expression regulation that consists of chemical modification of RNA species, which led to the birth of the epitranscriptomics field. RNA modifications provide an additional level of control in hematopoietic development by acting as post-transcriptional regulators of lineage-specific genetic programs. Other reviews have already described the important role of the N6-methylation of adenosine (m6A) within mRNA species in regulating hematopoietic differentiation and diseases. The aim of this review is to summarize the current status of the role of RNA modifications in the regulation of ribosome function, beyond m6A. In particular, we discuss the importance of RNA modifications in tRNA and rRNA molecules. By balancing translational rate and fidelity, they play an important role in regulating normal and malignant hematopoietic development. [ABSTRACT FROM AUTHOR]

This study aims to develop a reliable and reproducible inflammatory bowel disease (IBD) murine model based on a careful spatial–temporal histological characterization. Secondary aims included extensive preclinical studies focused on the in situ expression of clinically relevant biomarkers and targets involved in IBD. C57BL/6 female mice were used to establish the IBD model. Colitis was induced by the oral administration of 2% Dextran Sulfate Sodium (DSS) for 5 days, followed by 2, 4 or 9 days of water. Histological analysis was performed by sectioning the whole colon into rings of 5 mm each. Immunohistochemical analyses were performed for molecular targets of interest for monitoring disease activity, treatment response and predicting outcome. Data reported here allowed us to develop an original scoring method useful as a tool for the histological assessment of preclinical models of DSS-induced IBD. Immunohistochemical data showed a significant increase in TNF-α, α4β7, VEGFRII, GR-1, CD25, CD3 and IL-12p40 expression in DSS mice if compared to controls. No difference was observed for IL-17, IL-23R, IL-36R or F480. Knowledge of the spatial–temporal pattern distribution of the pathological lesions of a well-characterized disease model lays the foundation for the study of the tissue expression of meaningful predictive biomarkers, thereby improving translational success rates of preclinical studies for a personalized management of IBD patients. [ABSTRACT FROM AUTHOR]

β3-adrenoreceptor (β3-AR), a G-protein coupled receptor, has peculiar regulatory properties in response to oxygen and widespread localization. β3-AR is expressed in the most frequent neoplasms, also occurring in pregnant women, and its blockade reduces tumor growth, indicating β3-AR-blockers as a promising alternative to antineoplastic drugs during pregnancy. However, β3-AR involvement in prenatal morphogenesis and the consequences of its blockade for the fetus remain unknown. In this study, after the demonstrated expression of β3-AR in endothelial and smooth muscle cells of ductus arteriosus (DA), C57BL/6 pregnant mice were acutely treated at 18.5 of gestational day (GD) with indomethacin or with the selective β3-AR antagonist SR59230A, or chronically exposed to SR59230A from 15.5 to 18.5 GD. Six hours after the last treatment, fetuses were collected. Furthermore, newborn mice were treated straight after birth with BRL37344, a β3-AR agonist, and sacrificed after 7 h. SR59230A, at the doses demonstrated effective in reducing cancer progression (10 and 20 mg/kg) in acute and chronic mode, did not induce fetal DA constriction and did not impair the DA ability to close after birth, whereas at the highest dose (40 mg/kg), it was shown to cause DA constriction and preterm-delivery. BRL37344 administered immediately after birth did not alter the physiological DA closure. [ABSTRACT FROM AUTHOR]

Little is known about the quantity and quality of dissolved organic matter (DOM) in waters from continental geothermal systems, with only a few reports available from the Yellowstone US National Park. In this study, we explored the chemodiversity of DOM in water samples collected from two geothermal hot springs from the Kenyan East African Rift Valley, a region extremely rich in fumaroles, geysers, and spouting springs, located in close proximity to volcanic lakes. The DOM characterization included in-depth assessments performed by negative electrospray ionization Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR-MS). Reduced, saturated and little aromatic DOM compounds were dominant in the hot spring waters collected from either the Ol Njorowa gorge (ON) or the south shore of the soda-saline Lake Elementaita (ELM). Oxygen-poor and sulfur-bearing DOM molecules prevailed in ON, probably reflecting abiotic sulfurization from sulfide-rich geofluids. Nitrogen-bearing aliphatic and protein-like molecules were abundant in ELM, possibly perfusing through the organic-rich sediments of the adjacent Lake Elementaita. Notably, the heat-altered DOM of ancient autochthonous derivation could represent an overlooked source of aliphatic organic carbon for connected lentic environments, with a potential direct impact on nutrient cycling in lakes that receive geothermal water inputs. [ABSTRACT FROM AUTHOR]

One of the hallmarks of cellular transformation is the altered mechanism of cell death. There are three main types of cell death, characterized by different morphological and biochemical features, namely apoptosis (type I), autophagic cell death (type II) and necrosis (type III). Autophagy, or self-eating, is a tightly regulated process involved in stress responses, and it is a lysosomal degradation process. The role of autophagy in cancer is controversial and has been associated with both the induction and the inhibition of tumor growth. Autophagy can exert tumor suppression through the degradation of oncogenic proteins, suppression of inflammation, chronic tissue damage and ultimately by preventing mutations and genetic instability. On the other hand, tumor cells activate autophagy for survival in cellular stress conditions. Thus, autophagy modulation could represent a promising therapeutic strategy for cancer. Several studies have shown that polyphenols, natural compounds found in foods and beverages of plant origin, can efficiently modulate autophagy in several types of cancer. In this review, we summarize the current knowledge on the effects of polyphenols on autophagy, highlighting the conceptual benefits or drawbacks and subtle cell-specific effects of polyphenols for envisioning future therapies employing polyphenols as chemoadjuvants. [ABSTRACT FROM AUTHOR]

The survival rate for head and neck cancer patients has not substantially changed in the last two decades. We previously showed that two rV-neuT intratumoral injections induced an efficient antitumor response and rejection of transplanted Neu (rat ErbB2/neu oncogene-encoded protein)-overexpressing salivary gland tumor cells in BALB-neuT mice (BALB/c mice transgenic for the rat ErbB2/neu oncogene). However, reiterated poxviral vaccinations increase neutralizing antibodies to viral proteins in humans that prevent immune response against the recombinant antigen expressed by the virus. Curcumin (CUR) is a polyphenol with antineoplastic and immunomodulatory properties. The aim of this study was to employ CUR administration to boost the anti-Neu immune response and anticancer activity induced by one rV-neuT intratumoral vaccination in BALB-neuT mice. Here, we demonstrated that the combined rV-neuT+CUR treatment was more effective at reducing tumor growth and increasing mouse survival, anti-Neu humoral response, and IFN-γ/IL-2 T-cell release in vitro than the individual treatment. rV-neuT+CUR-treated mice showed an increased infiltration of CD4+/CD8+ T lymphocytes within the tumor as compared to those that received the individual treatment. Overall, CUR enhanced the antitumoral effect and immune response to Neu induced by the rV-neuT vaccine in mice. Thus, the combined treatment might represent a successful strategy to target ErbB2/Neu-overexpressing tumors. [ABSTRACT FROM AUTHOR]

Background: Tumor-associated macrophages (TAMs) constitute a major portion of the leukocyte infiltrate found in breast cancer (BC). BC cells may reprogram TAMs in a pro-angiogenic and immunosuppressive sense. We previously showed that high expression of the ID4 protein in triple-negative BC cells leads to the induction of a proangiogenic program in TAMs also through the downregulation of miR-107. Here, we investigated the expression and function of the ID4 protein in TAMs. Methods: Human macrophages obtained from peripheral blood-derived monocytes (PBDM) and mouse RAW264.7 cells were used as macrophage experimental systems. ID4-correlated mRNAs of the TCGA and E-GEOD-18295 datasets were analyzed. Results: We observed that BC cells determine a paracrine induction of ID4 expression and activation of the ID4 promoter in neighboring macrophages. Interestingly, ID4 expression is higher in macrophages associated with invasive tumor cells compared to general TAMs, and ID4-correlated mRNAs are involved in various pathways that were previously reported as relevant for TAM functions. Selective depletion of ID4 expression in macrophages enabled validation of the ability of ID4 to control the expression of YAP1 and of its downstream targets CTGF and CYR61. Conclusion: Collectively, our results show that activation of ID4 expression in TAMs is observed as a consequence of BC cell paracrine activity and could participate in macrophage reprogramming in BC. [ABSTRACT FROM AUTHOR]

NRF2 (NF-E2 p45-related factor 2) orchestrates cellular adaptive responses to stress. Its quantity and subcellular location is controlled through a complex network and its activity increases during redox perturbation, inflammation, growth factor stimulation, and energy fluxes. Even before all-trans retinoic acid (ATRA) treatment era it was a common experience that acute promyelocytic leukemia (APL) cells are highly sensitive to first line chemotherapy. Since we demonstrated how high doses of ascorbate (ASC) preferentially kill leukemic blast cells from APL patients, we aimed to define the underlying mechanism and found that promyelocytic leukemia/retinoic acid receptor α (PML/RARa) inhibits NRF2 function, impedes its transfer to the nucleus and enhances its degradation in the cytoplasm. Such loss of NRF2 function alters cell metabolism, demarcating APL tissue from both normal promyelocytes and other acute myeloide leukemia (AML) blast cells. Resistance to ATRA/arsenic trioxide (ATO) treatment is rare but grave and the metabolically-oriented treatment with high doses of ASC, which is highly effective on APL cells and harmless on normal hematopoietic stem cells (HSCs), could be of use in preventing clonal evolution and in rescuing APL-resistant patients. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is a primary brain tumor whose prognosis is inevitably dismal, leading patients to death in about 15 months from diagnosis. Tumor cells in the mass of the neoplasm are in continuous exchange with cells of the stromal microenvironment, through the production of soluble molecules, among which chemokines play prominent roles. CXCL14 is a chemokine with a pro-tumor role in breast and prostate carcinoma, where it is secreted by cancer associated fibroblasts, and contributes to tumor growth and invasion. We previously observed that CXCL14 expression is higher in GBM tissues than in healthy white matter. Here, we study the effects of exogenously supplemented CXCL14 on key tumorigenic properties of human GBM cell lines. We show that CXCL14 enhances the migration ability and the proliferation of U87MG and LN229 GBM cell lines. None of these effects was affected by the use of AMD3100, an inhibitor of CXCR4 receptor, suggesting that the observed CXCL14 effects are not mediated by this receptor. We also provide evidence that CXCL14 enhances the sphere-forming ability of glioblastoma stem cells, considered the initiating cells, and is responsible for tumor onset, growth and recurrence. In support of our in vitro results, we present data from several GBM expression datasets, demonstrating that CXCL14 expression is inversely correlated with overall survival, that it is enriched at the leading edge of the tumors and in infiltrating tumor areas, and it characterizes mesenchymal and NON G-CIMP tumors, known to have a particularly bad prognosis. Overall, our results point to CXCL14 as a protumorigenic chemokine in GBM. [ABSTRACT FROM AUTHOR]

Polyphenols are natural antioxidant compounds ubiquitously found in plants and, thus, ever present in human nutrition (tea, wine, chocolate, fruits and vegetables are typical examples of polyphenol-rich foods). Widespread evidence indicate that polyphenols exert strong antioxidant, anti-inflammatory, anti-microbial and anti-cancer activities, and thus, they are generally regarded to as all-purpose beneficial nutraceuticals or supplements whose use can only have a positive influence on the body. A closer look to the large body of results of years of investigations, however, present a more complex scenario where polyphenols exert different and, sometimes, paradoxical effects depending on dose, target system and cell type and the biological status of the target cell. Particularly, the immunomodulatory potential of polyphenols presents two opposite faces to researchers trying to evaluate their usability in future cancer therapies: on one hand, these compounds could be beneficial suppressors of peri-tumoral inflammation that fuels cancer growth. On the other hand, they might suppress immunotherapeutic approaches and give rise to immunosuppressive cell clones that, in turn, would aid tumor growth and dissemination. In this review, we summarize knowledge of the immunomodulatory effects of polyphenols with a particular focus on cancer microenvironment and immunotherapy, highlighting conceptual pitfalls and delicate cell-specific effects in order to aid the design of future therapies involving polyphenols as chemoadjuvants. [ABSTRACT FROM AUTHOR]

According to the psychology of sustainability and sustainable development, even though there are numerous challenges within the current labor market, it is possible to establish meaningful lives and meaningful work experiences through optimizing the use of personal resources and regenerating them. In line with this assumption, the present study aims to test the moderation effect of the type of worker contracts on the relationship between psychological capital, perceived employability, and job insecurity. Participants were N = 190 Italian young workers (self-employed, permanent employees, or temporary employees). Results showed that perceived employability mediated the relationship between psychological capital and job insecurity, and that this relationship was moderated by the workers’ type of contract. Specifically, a higher level of psychological capital corresponded to a higher perception of employability, and consequently a lower job insecurity for temporary and self-employed workers, but not for permanent ones. These findings are in line with the assumptions of the psychology of sustainability, and encourage preventive interventions aimed to foster personal resources in order to reduce job insecurity, especially in cases of non-standard employment. [ABSTRACT FROM AUTHOR]