Αρχειοθήκη ιστολογίου

Παρασκευή 22 Σεπτεμβρίου 2017

Vinegar production from fruit concentrates: effect on volatile composition and antioxidant activity

Abstract

Vinegar stands as a highly appreciated fermented food product due to several functional properties and multiple applications. This work focuses on vinegar production from fruit wines derived from fruit concentrates, to attain a food product with nutritional added value. Four fruit vinegars (orange, mango, cherry and banana), were produced and characterized, with total acidities of 5.3 ± 0.3% for orange, 5.6 ± 0.2% for mango, 4.9 ± 0.4% for cherry and 5.4 ± 0.4% for banana. Acetification showed impact on aroma volatiles, mainly related to oxidative reactions. Minor volatiles associated with varietal aroma were identified, monoterpenic alcohols in orange vinegar, esters in banana vinegar, C13-norisoprenoids in cherry vinegar and lactones in mango vinegar, indicating fruit vinegars differentiated sensory quality. Total antioxidant activity analysis by FRAP, revealed fruit vinegars potential to preserve and deliver fruit functional properties. Antioxidant activity of fruit vinegars, expressed as equivalents of Fe2SO4, was of 11.0 ± 1.67 mmol L−1 for orange, 4.8 ± 0.5 mmol L−1 for mango, 18.6 ± 2.33 mmol L−1 for cherry and 3.7 ± 0.3 mmol L−1 for banana. Therefore, fruit vinegars presented antioxidant activity close to the reported for the corresponding fruit, and between 8 and 40 folds higher than the one found in commercial cider vinegar, demonstrating the high functional potential of these novel vinegar products.



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Classification of whole wheat flour using a dimensionless number

Abstract

The rheological standards currently used for classifying refined wheat flour for technological quality of bread are also used for whole wheat flours. The aim of this study was to evaluate the rheological and technological behavior of different whole wheat flours, as well as pre-mixes of refined wheat flour with different replacement levels of wheat bran, to develop a dimensionless number that assigns a numerical scale using results of rheological parameters to solve this problem. Through farinograph and extensograph results, most whole wheat flours evaluated presented parameters recommended for bread making, according to the current classification. However, the specific volume of breads elaborated with these flours was not suitable, that is, the rheological analyses were not able to predict the specific volume of pan bread. The development of the Sehn–Steel dimensionless number allowed establishing a classification of whole wheat flours as "suitable" (Sehn–Steel dimensionless number between 62 and 200) or "unsuitable" for the production of pan bread (Sehn–Steel dimensionless number lower than 62). Moreover, an equation that can predict the specific volume of whole pan bread through this dimensionless number was developed.



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Boosted coupling of ATP hydrolysis to substrate transport upon cooperative estradiol-17-{beta}-D-glucuronide binding in a Drosophila ATP binding cassette type-C transporter [Research]

ATP binding cassette type-C (ABCC) transporters move molecules across cell membranes upon hydrolysis of ATP; however, their coupling of ATP hydrolysis to substrate transport remains elusive. Drosophila multidrug resistance-associated protein (DMRP) is the functional ortholog of human long ABCC transporters, with similar substrate and inhibitor specificity, but higher activity. Exploiting its high activity, we kinetically dissected the catalytic mechanism of DMRP by using E2-d-glucuronide (E2G), the physiologic substrate of human ABCC. We examined the DMRP-mediated interdependence of ATP and E2G in biochemical assays. We observed E2G-dependent ATPase activity to be biphasic at subsaturating ATP concentrations, which implies at least 2 E2G binding sites on DMRP. Furthermore, transport measurements indicated strong nonreciprocal cooperativity between ATP and E2G. In addition to confirming these findings, our kinetic modeling with the Complex Pathway Simulator indicated a 10-fold decrease in the E2G-mediated activation of ATP hydrolysis upon saturation of the second E2G binding site. Surprisingly, the binding of the second E2G allowed for substrate transport with a constant rate, which tightly coupled ATP hydrolysis to transport. In summary, we show that the second E2G binding—similar to human ABCC2—allosterically stimulates transport activity of DMRP. Our data suggest that this is achieved by a significant increase in the coupling of ATP hydrolysis to transport.—Karasik, A., Ledwitch, K. V., Arányi, T., Váradi, A., Roberts, A., Szeri, F. Boosted coupling of ATP hydrolysis to substrate transport upon cooperative estradiol-17-β-D-glucuronide binding in a Drosophila ATP binding cassette type-C transporter.



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miR-125a-3p inhibits ER{alpha} transactivation and overrides tamoxifen resistance by targeting CDK3 in estrogen receptor-positive breast cancer [Research]

Tamoxifen (TAM) is a major adjuvant therapy for patients who are diagnosed with estrogen receptor-α (ER)–positive breast cancer; however, TAM resistance occurs often during treatment and the underlying mechanism is unclear. Here, we report that miR-125a-3p inhibits ERα transcriptional activity and, thus, ER+ breast cancer cell proliferation, which causes cell-cycle arrest at the G1/S stage, inducing apoptosis and suppressing tumor growth by targeting cyclin-dependent kinase 3 (CDK3) in vitro and in vivo. In addition, CDK3 and miR-125a-3p expression levels were measured in 37 cancerous tissues paired with noncancerous samples, and their expression levels were negatively associated with miR-125a-3p level. Of interest, miR-125a-3p level is down-regulated in MCF-7 TAM-resistant (TamR) cells. Of more importance, up-regulation of miR-125a-3p resensitizes MCF-7 TamR cells to TAM, which is dependent on CDK3 expression. These results suggest that miR-125a-3p can function as a novel tumor suppressor in ER+ breast cancer by targeting CDK3, which may be a potential therapeutic approach for TamR breast cancer therapy.—Zheng, L., Meng, X., Li, X., Zhang, Y., Li, C., Xiang, C., Xing, Y., Xia, Y., Xi, T. miR-125a-3p inhibits ERα transactivation and overrides tamoxifen resistance by targeting CDK3 in estrogen receptor–positive breast cancer.



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Cic loss promotes gliomagenesis via aberrant neural stem cell proliferation and differentiation

Inactivating mutations in the transcriptional repression factor Capicua (CIC) occur in ~50% of human oligodendrogliomas (OD), but mechanistic links to pathogenesis are unclear. To address this question, we generated Cic-deficient mice and human OD cell models. Genetic deficiency in mice resulted in a partially penetrant embryonic or perinatal lethal phenotype, with the production of an aberrant proliferative neural population in surviving animals. In vitro cultured neural stem cells derived from Cic conditional knockout mice bypassed an EGF requirement for proliferation and displayed a defect in their potential for oligodendrocyte differentiation. Cic is known to participate in gene suppression that can be relieved by EGFR signal, but we found that cic also activated expression of a broad range of EGFR-independent genes. In an orthotopic mouse model of glioma, we found that Cic loss potentiated the formation and reduced the latency in tumor development. Collectively, our results define an important role for CiC in regulating neural cell proliferation and lineage specification, and suggest mechanistic explanations for how CIC mutations may impact the pathogenesis and therapeutic targeting of oligodendroglioma.

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Mobilizing transit-amplifying cell-derived ectopic progenitors prevents hair loss from chemotherapy or radiation therapy

Genotoxicity-induced hair loss from chemotherapy and radiotherapy is often encountered in cancer treatment, and there is a lack of effective treatment. In growing hair follicles (HF), quiescent stem cells (SC) are maintained in the bulge region and hair bulbs at the base contain rapidly dividing, yet genotoxicity-sensitive transit-amplifying cells (TAC) that maintain hair growth. How genotoxicity-induced HF injury is repaired remains unclear. We report here that HF mobilize ectopic progenitors from distinct TAC compartments for regeneration in adaptation to the severity of dystrophy induced by ionizing radiation (IR). Specifically, after low-dose IR, keratin5+ basal hair bulb progenitors, rather than bulge SC, were quickly activated to replenish matrix cells and regenerated all concentric layers of HF, demonstrating their plasticity. After high-dose IR, when both matrix and hair bulb cells were depleted, the surviving outer root sheath cells rapidly acquired a SC-like state and fueled HF regeneration. Their progeny then homed back to SC niche and supported new cycles of HF growth. We also revealed that IR induced HF dystrophy and hair loss and suppressed WNT signaling in a p53- and dose-dependent manner. Augmenting WNT signaling attenuated the suppressive effect of p53 and enhanced ectopic progenitor proliferation after genotoxic injury, thereby preventing both IR- and cyclophosphamide-induced alopecia. Hence, targeted activation of TAC-derived progenitor cells, rather than quiescent bulge SC, for anagen HF repair can be a potential approach to prevent hair loss from chemotherapy and radiotherapy.

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Next-generation sequencing in the clinical setting clarifies patient characteristics and potential actionability

Enhancements in clinical-grade next-generation sequencing (NGS) have fueled the advancement of precision medicine in the clinical oncology field. Here we survey the molecular profiles of 1,113 patients with diverse malignancies who successfully underwent clinical-grade NGS (236 to 404 genes) in an academic tertiary cancer center. Among the individual tumors examined, the majority showed at least one detectable alteration (97.2%). Amongst 2,045 molecular aberrations was involvement of 302 distinct genes. The most commonly altered genes were TP53 (47.0%), CDKN2A (18.0%), TERT (17.0%), and KRAS (16.0%), and the majority of patients had tumors that harbored multiple alterations. Tumors displayed a median of four alterations (range, 0-29). Most individuals had at least one potentially actionable alteration (94.7%), with the median number of potentially actionable alterations per patient being 2 (range, 0-13). A total of 94.2% patients exhibited a unique molecular profile, with either genes altered or loci within the gene(s) altered being distinct. Approximately 13% of patients displayed a genomic profile identical to at least one other patient; although genes altered were the same, the affected loci may have differed. Overall, our results underscore the complex heterogeneity of malignancies and argue that customized combination therapies will be essential to optimize cancer treatment regimens.

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R-Spondin1/LGR5 Activates TGF{beta} Signaling and Suppresses Colon Cancer Metastasis

Leucine rich repeat containing G protein-coupled receptor 5 (LGR5), an intestinal stem cell marker is known to exhibit tumor suppressor activity in colon cancer, the mechanism of which is not understood. Here we show that R-spondin 1 (RSPO1)/LGR5 directly activates TGFβ signaling cooperatively with TGFβ type II receptor in colon cancer cells, enhancing TGFβ-mediated growth inhibition and stress-induced apoptosis. Knockdown of LGR5 attenuated downstream TGFβ signaling and increased cell proliferation, survival, and metastasis in an orthotopic model of colon cancer in vivo. Upon RSPO1 stimulation, LGR5 formed complexes with TGFβ receptors. Studies of patient specimens indicate that LGR5 expression was reduced in advanced stages and positively correlated with markers of TGFβ activation in colon cancer. Our study uncovers a novel crosstalk between LGR5 and TGFβ signaling in colon cancer and identifies LGR5 as a new modulator of TGFβ signaling able to suppress colon cancer metastasis.

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HIF-2alpha: Achilles' heel of pseudohypoxic subtype paraganglioma and other related conditions

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Publication date: November 2017
Source:European Journal of Cancer, Volume 86
Author(s): Sri Harsha Tella, David Taïeb, Karel Pacak
Paragangliomas (PGLs) belong to the most hereditary endocrine tumours. The existence of mutated HIF2A in these tumours, the role of oncometabolites on HIFs stabilisation and a recent concept proposing how hereditary PGLs converge on the hypoxia-signalling pathway, brought solid evidence of the existence of PGL hypoxiom. Hypoxia-inducible factor 2alpha (HIF-2α) antagonists -PT2385, and PT2399 have been shown to have promising results in the management of clear cell renal cell carcinoma by targeting the HIF-2α pathway in recent and ongoing clinical trials (PT2799). The main aim of this perspective is to address the possibility of HIF-2α antagonists in the management of tumours, beyond clear cell renal cell carcinoma, where the dysfunctional hypoxia-signalling pathway, especially HIF-2α, referred here as the Achilles' heel, plays a unique role in tumorigenesis and other disorders. These tumours or disorders include PGLs, somatostatinomas, hemangioblastomas, gastrointestinal stromal tumours, pituitary tumours, leiomyomas/leiomyosarcomas, polycythaemia and retinal abnormalities. We hope that HIF-2α antagonists are likely to emerge as a potential effective treatment of choice for HIF-2α–related tumours and disorders.



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Extraskeletal osteosarcoma in the parotid gland: A case report

Extraskeletal osteosarcoma is a very rare tumor and accounts for 4–5% of all osteosarcomas. We describe a 47-year-old Japanese man who presented with a right parotid tumor. The patient underwent total resection with postoperative radiotherapy; however, the tumor recurred in the lung, whereupon he underwent chemotherapy and partial lung resection. After surgery, a hemorrhagic brain metastasis appeared; this tumor was extirpated to prevent bleeding into the brain, after which additional chemotherapy was administered.

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3D-constructive interference into steady state (3D-CISS) labyrinth signal alteration in patients with vestibular schwannoma

To evaluate signal intensity of the inner ear using 3D-CISS imaging and correlated signal characteristics in patients with vestibular schwannoma to neuro-otological symptoms.

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High-dose corticosteroids improve the prognosis of Bell’s palsy compared with low-dose corticosteroids: A propensity score analysis

The aim of this study was to evaluate the effectiveness of high-dose corticosteroid (120mg prednisolone equivalent daily) in Bell's palsy compared with low-dose corticosteroid (60mg PSL equivalent).

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Microbial inositol polyphosphate metabolic pathway as drug development target

Publication date: Available online 22 September 2017
Source:Advances in Biological Regulation
Author(s): Adolfo Saiardi, Cristina Azevedo, Yann Desfougères, Paloma Portela-Torres, Miranda S.C. Wilson
Inositol polyphosphates are a diverse and multifaceted class of intracellular messengers omnipresent in eukaryotic cells. These water-soluble molecules regulate many aspects of fundamental cell physiology. Removing this metabolic pathway is deleterious: inositol phosphate kinase null mutations can result in lethality or substantial growth phenotypes. Inositol polyphosphate synthesis occurs through the actions of a set of kinases that phosphorylate phospholipase-generated IP3 to higher phosphorylated forms, such as the fully phosphorylated IP6 and the inositol pyrophosphates IP7 and IP8. Unicellular organisms have a reduced array of the kinases for synthesis of higher phosphorylated inositol polyphosphates, while human cells possess two metabolic routes to IP6. The enzymes responsible for inositol polyphosphate synthesis have been identified in all eukaryote genomes, although their amino acid sequence homology is often barely detectable by common search algorithms. Homology between human and microbial inositol phosphate kinases is restricted to a few catalytically important residues. Recent studies of the inositol phosphate metabolic pathways in pathogenic fungi (Cryptococcus neoformans) and protozoa (Trypanosome brucei) have revealed the importance of the highly phosphorylated inositol polyphosphates to the fitness and thus virulence of these pathogens. Given this, identification of inositol kinase inhibitors specifically targeting the kinases of pathogenic microorganisms is desirable and achievable.



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Splicing factor mutations in the myelodysplastic syndromes: Target genes and therapeutic approaches

Publication date: Available online 22 September 2017
Source:Advances in Biological Regulation
Author(s): Richard N. Armstrong, Violetta Steeples, Shalini Singh, Andrea Sanchi, Jacqueline Boultwood, Andrea Pellagatti
Mutations in splicing factor genes (SF3B1, SRSF2, U2AF1 and ZRSR2) are frequently found in patients with myelodysplastic syndromes (MDS), suggesting that aberrant spliceosome function plays a key role in the pathogenesis of MDS. Splicing factor mutations have been shown to result in aberrant splicing of many downstream target genes. Recent functional studies have begun to characterize the splicing dysfunction in MDS, identifying some key aberrantly spliced genes that are implicated in disease pathophysiology. These findings have led to the development of therapeutic strategies using splicing-modulating agents and rapid progress is being made in this field. Splicing inhibitors are promising agents that exploit the preferential sensitivity of splicing factor-mutant cells to these compounds. Here, we review the known target genes associated with splicing factor mutations in MDS, and discuss the potential of splicing-modulating therapies for these disorders.



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Extraskeletal osteosarcoma in the parotid gland: A case report

Extraskeletal osteosarcoma is a very rare tumor and accounts for 4–5% of all osteosarcomas. We describe a 47-year-old Japanese man who presented with a right parotid tumor. The patient underwent total resection with postoperative radiotherapy; however, the tumor recurred in the lung, whereupon he underwent chemotherapy and partial lung resection. After surgery, a hemorrhagic brain metastasis appeared; this tumor was extirpated to prevent bleeding into the brain, after which additional chemotherapy was administered.

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3D-constructive interference into steady state (3D-CISS) labyrinth signal alteration in patients with vestibular schwannoma

To evaluate signal intensity of the inner ear using 3D-CISS imaging and correlated signal characteristics in patients with vestibular schwannoma to neuro-otological symptoms.

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High-dose corticosteroids improve the prognosis of Bell’s palsy compared with low-dose corticosteroids: A propensity score analysis

The aim of this study was to evaluate the effectiveness of high-dose corticosteroid (120mg prednisolone equivalent daily) in Bell's palsy compared with low-dose corticosteroid (60mg PSL equivalent).

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A Vocal Health Survey Among Amateur and Professional Voice Users

An international survey was conducted to provide insights into current practices related to vocal health among amateur and professional voice users. Vocalists of various genres completed an online survey related to their practice in seeking medical care for vocal health concerns, and their preferences for the type of medical help they seek. Specific vocal symptoms or conditions which the subjects feel would warrant evaluation was also queried, as well as their preference for voice use and management should laryngeal pathology be diagnosed during a medical examination.

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Re: Androgen deprivation therapy and cardiovascular risk: No meaningful difference between GnRH antagonist and agonists

I read with interest, the recently published manuscript by Scailteux et al., investigating whether cardiovascular risks differ by the type of androgen deprivation therapy selected in men with newly treated prostate cancer [1]. The authors specifically cited our analysis (ref 14) which raised the hypothesis that Gonadotropin Releasing Hormone (GnRH) antagonists may lower cardiovascular risks when compared with agonists but neglected to test our full hypothesis that this difference occurs primarily in men with pre-existing cardiovascular disease [2].

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Biological control of wilt disease complex on tomato crop caused by Meloidogyne javanica and Fusarium oxysporum f.sp. lycopersici by Verticillium leptobactrum

Abstract

The efficacy of Verticillium leptobactrum isolate (HR1) was evaluated in the control of root-knot nematode and Fusarium wilt fungus under laboratory and greenhouse conditions. Five concentrations of V. leptobactrum (HR1) isolate were tested for their nematicidal and fungicidal activities against Meloidogyne javanica and Fusarium oxysporum f.sp. lycopersici in vitro. Laboratory trials showed that mycelium growth inhibition of Fusarium wilt fungus was correlated to the increase of the concentration of culture filtrate. All dilutions showed efficiency in reducing the growth of Fusarium oxysporum f.sp. lycopersici. The greatest nematicidal activity was observed at 50, 75, and 100% filtrate dilutions. The egg hatching percentage reached 42%, and the juvenile's corrected mortality registered 90% for the above treatments. In greenhouse experiment, the biocontrol agent fungus enhanced significantly tomato growth components (height and weight of plant and root). The multiplication rate of root-knot nematode and the Fusarium wilt disease incidence declined significantly with soil application of V. leptobactrum as with chemical treatments. The isolate HR1 was efficient to control wilt disease complex caused by M. javanica and Fusarium oxysporum f.sp. lycopersici.



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