Publications by authors named "Notario V"

This study investigates the eco-friendly extraction of metal oxides from LCO and NMC batteries using supercritical water. Experiments were conducted at 450 °C with a feed rate of 5 mL min and varying battery/PVC ratios (0.0, 2.

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The microbiota present in the gastrointestinal tract is involved in the development or prevention of food allergies and autoimmune disorders; these bacteria can enter the gallbladder and, depending on the species involved, can either be benign or cause significant diseases. Occlusion of the gallbladder, usually due to the presence of calculi blocking the bile duct, facilitates microbial infection and inflammation, which can be serious enough to require life-saving surgery. In addition, the biliary salts are secreted into the intestine and can affect the gut microbiota.

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Phages have certain features, such as their ability to form protein-protein interactions, that make them good candidates for use in a variety of beneficial applications, such as in human or animal health, industry, food science, food safety, and agriculture. It is essential to identify and characterize the proteins produced by particular phages in order to use these viruses in a variety of functional processes, such as bacterial detection, as vehicles for drug delivery, in vaccine development, and to combat multidrug resistant bacterial infections. Furthermore, phages can also play a major role in the design of a variety of cheap and stable sensors as well as in diagnostic assays that can either specifically identify specific compounds or detect bacteria.

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Radiation therapy has been used for more than a century, either alone or in combination with other therapeutic modalities, to treat most types of cancer. On average, radiation therapy is included in the treatment plans for over 50% of all cancer patients, and it is estimated to contribute to about 40% of curative protocols, a success rate that may reach 90%, or higher, for certain tumor types, particularly on patients diagnosed at early disease stages. A growing body of research provides solid support for the existence of bidirectional interaction between radiation exposure and the human microbiota.

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Esophageal cancer has a strikingly low survival rate mainly due to the lack of diagnostic markers for early detection and effective therapies. In the U.S.

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Cancer is predominantly considered as an environmental disease caused by genetic or epigenetic alterations induced by exposure to extrinsic (e.g., carcinogens, pollutants, radiation) or intrinsic (e.

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Despite increased use of early detection methods and more aggressive treatment strategies, the worldwide incidence of colorectal cancer is still on the rise. Consequently, it remains urgent to identify novel agents with enhanced efficacy in prevention and/or therapeutic protocols. Our studies focused on the use of Plumbagin, a natural phytochemical that showed promising results against other tumor types, to determine its effectiveness in blocking the proliferation and survival of colon cancer cells in experimental protocols mimicking the environment in primary tumors (attached culture conditions) and in circulating tumor cells (unattached conditions).

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Expression of the ENTPD5/mt-PCPH onco-protein and overexpression of the normal ENTPD5/PCPH protein contribute to the malignant transformation of diverse mammalian cell types, and PCPH is mutated and/or deregulated in various human tumor types. Expression of PCPH or mt-PCPH caused similar phenotypes, yet the effects promoted by mt-PCPH expression were consistently and substantially greater. ATP depletion and increased stress‑resistance are phenotypes commonly associated with PCPH and mt-PCPH expression.

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Article Synopsis
  • * The chimeric protein EWS/FLI1 drives the malignancy in EWS by regulating genes related to cell cycle progression, making it a potential target for treatment.
  • * The study found that thiostrepton, a small molecule, can inhibit both FoxM1 and EWS/FLI1 proteins, leading to cell cycle arrest, apoptosis in EWS cells, and reduced tumor growth in mouse models, suggesting its promise as a novel treatment for EWS patients.
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The potent actions of pigment epithelium-derived factor (PEDF) on tumour-associated cells, and its extracellular localization and secretion, stimulated research on this multifunctional serpin. Such studies have identified several PEDF receptors and downstream signalling pathways. Known cellular PEDF responses have expanded from the initial discovery that PEDF induces retinoblastoma cell differentiation to its anti-angiogenic, antitumorigenic and antimetastatic properties.

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Purpose: Pigment epithelium-derived factor (PEDF) is a multifunctional serpin. The purpose of this study is to identify PEDF protein forms and investigate their biological activities on tumor cell lines.

Methods: Recombinant human PEDF proteins were purified by cation- and anion-exchange column chromatography.

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Recently, we have shown that the antiangiogenic pigment epithelium-derived factor (PEDF) can bind the catalytic β-subunit of F1-ATP synthase and inhibit endothelial cell surface ATP synthase activity. This factor can additionally restrict tumor growth, invasion and metastasis, and can directly induce death on several tumor cell types. Active cell surface ATP synthase is also present in certain tumor cells and its ATP product is considered a stimulus for tumor growth.

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Type 11 hydroxysteroid (17-beta) dehydrogenase (HSD17B11) catalyzes the conversion of 5α-androstan-3α,17β-diol into androsterone suggesting that it may play an important role in androgen metabolism. We previously described that overexpression of C/EBPα or C/EBPβ induced HSD17B11 expression in HepG2 cells but this process was not mediated by the CCAAT boxes located within its proximal promoter region. Here, we study HSD17B11 transcriptional regulation in prostate cancer (PC) cells.

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Article Synopsis
  • - Caveolin-1 (CAV1) levels are significantly high in Ewing's sarcoma (EWS), influencing the tumor's growth, drug resistance, and spread.
  • - Prior studies showed that CAV1, secreted by certain cancer cells, is linked to tumor advancement, prompting an investigation into whether EWS cells also secrete CAV1.
  • - Experiments confirmed that EWS cells not only secrete CAV1 but also absorb it from their environment, with extracellular CAV1 promoting increased cell proliferation, suggesting it may worsen the cancer's aggressive characteristics.
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  • Metastasis is a critical stage in tumor progression, responsible for up to 90% of solid tumor-related deaths, and the study focuses on how Caveolin-1 (CAV1) influences metastasis in Ewing's sarcoma family tumors (ESFT).
  • Analysis of tumor samples revealed that all metastatic ESFT had high levels of CAV1 expression, indicating a potential correlation between CAV1 and enhanced metastatic ability.
  • Experiments showed that reducing CAV1 expression in ESFT cells significantly decreased their ability to migrate and invade, and in mice, CAV1-knockdown cells had either delayed or no lung metastasis, pointing to CAV1's crucial role in regulating these cancer processes through mechanisms such
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Biologically active membrane gangliosides, expressed and released by many human tumors, are hypothesized to significantly impact tumor progression. Lack of a model of complete and specific tumor ganglioside depletion in vivo, however, has hampered elucidation of their role. Here, we report the creation of a novel, stable, genetically induced tumor cell system resulting in specific and complete blockade of ganglioside synthesis.

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Article Synopsis
  • Caveolin-1 (CAV1) plays a key role in the drug resistance of Ewing's Sarcoma Family Tumors (ESFT) by affecting the sensitivity of cancer cells to chemotherapy.
  • Higher levels of CAV1 in ESFT cells lead to increased resistance to drugs like doxorubicin and cisplatin, while knocking down CAV1 makes the cells more sensitive to these treatments.
  • Targeting CAV1 and its related pathway (phospho(Thr(638))-PKCalpha) could lead to new treatment strategies for improving outcomes in ESFT patients.
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  • Researchers are exploring CDK inhibitors for their therapeutic potential, with (R)-roscovitine showing selectivity and low toxicity in clinical trials.
  • To enhance its effectiveness, the team synthesized new compounds and discovered that one, named GP0210, is more potent at inhibiting CDKs and inducing cancer cell death than (R)-roscovitine.
  • This could lead to the development of improved second generation CDK inhibitors with greater biomedical benefits.
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Prostate cancer (PCa) frequently develops antiapoptotic mechanisms and acquires resistance to anticancer drugs. Therefore, identifying PCa drug resistance determinants should facilitate designing more effective chemotherapeutic regimens. Recently, we described that the PCPH protein becomes highly expressed in human prostatic intraepithelial neoplasia and in PCa, and that the functional interaction between PCPH and protein kinase Cdelta (PKCdelta) increases the invasiveness of human PCa.

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Pigment epithelium-derived factor (PEDF) is a multifunctional serpin with antitumorigenic, antimetastatic, and differentiating activities. PEDF is found within tissues rich in the glycosaminoglycan hyaluronan (HA), and its amino acid sequence contains putative HA-binding motifs. We show that PEDF coprecipitation with glycosaminoglycans in media conditioned by human retinoblastoma Y-79 cells decreased after pretreatments with hyaluronidase, implying an association between HA and PEDF.

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Previous reports showed that PCPH is mutated or deregulated in some human tumors, suggesting its participation in malignant progression. Immunohistochemical analyses showed that PCPH is not expressed in normal prostate, but its expression increases along cancer progression stages, being detectable in benign prostatic hyperplasia, highly expressed in prostatic intraepithelial neoplasia, and remaining at high levels in prostate carcinoma. Experiments designed to investigate the contribution of PCPH to the malignant phenotype of prostate cancer cells showed that PCPH overexpression in PC-3 cells, which express nearly undetectable PCPH levels, increased collagen I expression and enhanced invasiveness, whereas shRNA-mediated PCPH knockdown in LNCaP cells, which express high PCPH levels, down-regulated collagen I expression and decreased invasiveness.

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  • Protein kinases are key targets for cancer treatment, and meriolins, a new family of inhibitors targeting cyclin-dependent kinases (CDKs), demonstrate enhanced specificity and potency for CDK2 and CDK9 compared to the existing inhibitor variolin B.
  • The structure of meriolins shows they bind to the ATP site of CDKs but differ in orientation from variolin B, leading to better antiproliferative and proapoptotic effects in human tumor cell cultures.
  • In preclinical studies on mouse cancer models, meriolin 3 effectively inhibits tumor growth and has been shown to induce apoptosis through mechanisms involving Mcl-1 down-regulation and caspase activation.
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  • - The study aimed to evaluate the effectiveness of using antisense oligonucleotides targeting EWS/FLI-1 along with rapamycin to control Ewing's sarcoma (EWS) cell growth both in lab cultures and in mouse models.
  • - Results showed that this combination treatment activated a process leading to apoptosis (cell death) in EWS cells and significantly inhibited tumor growth in mice, with the combined treatment being more effective than using each treatment alone.
  • - The findings highlight the potential of this combined therapy as a new approach for treating Ewing's sarcoma, warranting further research into its effectiveness and application.
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Article Synopsis
  • Ewing's sarcoma family tumors (ESFT), including Ewing's sarcoma and primitive neuroectodermal tumors, are aggressive cancers mainly affecting young individuals and are driven by abnormal proteins formed from the fusion of the EWS gene with ETS genes.
  • Research has identified caveolin-1 (CAV1) as a direct target of the EWS/FLI-1 protein, which is overexpressed in ESFT and essential for tumor development; knocking down CAV1 disrupts tumor growth by affecting related proteins like Snail and E-cadherin.
  • The findings indicate that CAV1 plays a critical role in cancer progression and suggest that targeting CAV1 could lead to new treatment options for
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Raf-1 serine/threonine protein kinase plays an important role in cell growth, differentiation and cell survival. Recent reports using c-raf-1 gene-knockouts have observed MEK/ERK independent functions of Raf-1 in cell survival and protection from apoptosis. Raf-1 has also been shown to be involved in counteracting specific apoptotic pathways by restraining caspase activation, although the precise mechanism is unknown.

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