Publications by authors named "Villagra A"

Histone deacetylase 6 (HDAC6) inhibition is associated with an increased pro-inflammatory tumor microenvironment and antitumoral immune responses. Here, we show that the HDAC6 inhibitor AVS100 (SS208) had an antitumoral effect in SM1 melanoma and CT26 colon cancer models and increased the efficacy of anti-programmed cell death protein 1 treatment, leading to complete remission in melanoma and increased response in colon cancer. AVS100 treatment increased pro-inflammatory tumor-infiltrating macrophages and CD8 effector T cells with an inflammatory and T cell effector gene signature.

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Background: Macrophage-based cell therapies have shown modest success in clinical trials, which can be attributed to their phenotypic plasticity, where transplanted macrophages get reprogrammed towards a pro-tumor phenotype. In most tumor types, including melanoma, the balance between antitumor M1-like and tumor-promoting M2-like macrophages is critical in defining the local immune response with a higher M1/M2 ratio favoring antitumor immunity. Therefore, designing novel strategies to increase the M1/M2 ratio in the TME has high clinical significance and benefits macrophage-based cell therapies.

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The adolescent population with Down syndrome (DS) appears to show higher levels of body fat and lower levels of cardiorespiratory fitness or muscle strength than their peers without disabilities. There is a need to create physical activity programs to improve these data. The aim of this research was to determine the effects of a 16-week swimming program, strength program, and combined program (swimming and strength training) on body composition and health-related physical fitness on adolescents with DS and to assess whether there are differences in the results of the different training programs.

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We compared the effects of milk-feeding in 288 Holstein calves (72 per group) which were fed twice (2F) or thrice (3F) daily, with or without the addition of hydrogenated fat-embedded calcium gluconate (G) supplemented in the starter food and in the daily diet up to the age of 9 months, on the calves' metabolism, growth, health, and reproductive efficiency up to first pregnancy. The calves received 6 L of milk replacer (130 g/L) and had ad libitum access to water and textured calf starter with or without gluconate. Gluconate supplementation promoted a "catch-up" in growth in supplemented calves compared to their counterparts that did not receive gluconate.

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  • Cancer cells can overexpress CD47, blocking immune responses by preventing macrophages from eliminating them; this study focuses on how HDAC6 inhibitors (like Nexturastat A) can affect this process.
  • Researchers tested HDAC6 inhibitors on macrophages to see how these drugs can modify the CD47/SIRPα interaction and increase phagocytosis, with experiments conducted in both lab settings and mouse models.
  • The findings showed that HDAC6 inhibitors promote a shift toward antitumoral macrophages, reducing SIRPα levels and CD47 expression, ultimately enhancing the macrophages' ability to phagocytose melanoma cells when combined with anti-CD47 antibodies.
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Non-contact devices have been used in the measurement of body temperature in livestock production as a tool for testing disease in different species. However, there are few studies about the variation and correlations in body temperature between rectal temperature (RT) and non-contact devices such as non-contact infrared thermometers (NCIT) and thermal imaging/infrared thermography (IRT). The objective of this work was to evaluate the accuracy of non-contact devices to measure the body temperature in sheep, considering six body regions and the possibility of implementing these systems in herd management.

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Colorectal cancer (CRC) is one of the most common malignant neoplasms and the second leading cause of death from tumors worldwide. Therefore, there is a great need to study new therapeutical strategies, such as effective immunotherapies against these malignancies. Unfortunately, many CRC patients do not respond to current standard immunotherapies, making it necessary to search for adjuvant treatments.

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  • Radiotherapy damages cellular DNA and promotes antitumor immunity, but it can also lead to the conversion of beneficial M1 macrophages into pro-cancer M2 macrophages over time, increasing the risk of tumor relapse.
  • Histone deacetylase 6 (HDAC6) is critical in regulating the polarization of macrophages and innate immune responses.
  • Targeting HDAC6 with a new selective inhibitor (SP-2-225) shows promise in improving antitumor immune responses and reducing tumor growth when used alongside radiotherapy.
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Aims: to determine the effect of a 20-week exergame program on different indicators of body composition and components of health-related physical fitness in adolescents with Down syndrome. Methods and Procedures Outcomes: 49 adolescents (19 female and 30 males; average age, 14.19 ± 2.

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  • Calves are highly vulnerable to stress in their early life stages, making effective feeding management essential for their health and welfare.
  • A systematic review analyzed 1,783 studies, narrowing it down to 351 that focused on calf management and welfare, highlighting gaps in current knowledge.
  • Key areas of focus included feeding strategies, especially regarding colostrum and weaning management, revealing the need for clearer protocols to minimize stress and enhance calf welfare.
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Introduction: Raising a healthy calf up to puberty is essential for optimal farm performance. It is therefore, it is necessary to promote animal welfare from the three spheres during this short period. Social management has been postulated as essential in lowering stress and consequently improving calf welfare during this period.

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Progesterone (P4) concentrations in canines are exceptionally high in the periovulatory period. However, the mechanisms by which P4 modulates final oocyte development in dogs remain to be characterized. The aim of this study was to evaluate the effect of P4 on meiotic development related to the gene expression of connexin 37 (Cx37) and connexin 43 (Cx43) in the canine cumlus oocyte complexes (COCs).

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A high intramuscular fat content characterizes Wagyu (WY) cattle breed. Our objective was to compare beef from WY, WY-by-Angus, or Wangus (WN) steers with European, Angus-by-Charolais-Limousine crossbred steers (ACL), considering metabolic biomarkers pre-slaughtering and nutritional characteristics, including health-related indexes of the lipid fraction. The fattening system with olein-rich diets and no exercise restriction included 82 steers, 24 WY, 29 WN, and 29 ACL.

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To determine the effect of a 16-week fitness program (strength vs. aerobic) on different indicators of body composition and components of health-related physical fitness in youths with Down syndrome. Fifty adolescents (19 girls and 31 boys; average age, 18.

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Purpose: Radiotherapy is a curative therapeutic modality used to treat cancers as a single agent or in combination with surgery and chemotherapy. Advanced radiotherapy technologies enable treatment with large fractions and highly conformal radiation doses to effect free-radical damage to cellular DNA leading to cell-cycle arrest, cell death, and innate immune response (IIR) stimulation.

Experimental Design: To understand systemic clinical responses after radiation exposure, proteomic and metabolomic analyses were performed on plasma obtained from patients with cancer at intervals after prostate stereotactic body radiotherapy.

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  • Antimicrobial resistance is a big health problem and could cause many deaths by 2050.
  • A study looked at whether adding antibiotics to rabbit feed helps with their health and growth during their growing period.
  • The findings showed that using antibiotics in rabbit feed didn’t change their gut bacteria or how well they grew, suggesting that breeding stronger rabbits could be a better solution than using antibiotics.
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Background: Novel therapies are urgently needed for ovarian cancer (OC), the fifth deadliest cancer in women. Preclinical work has shown that DNA methyltransferase inhibitors (DNMTis) can reverse the immunosuppressive tumor microenvironment in OC. Inhibiting DNA methyltransferases activate transcription of double-stranded (ds)RNA, including transposable elements.

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Despite the promise of immunotherapy such as the immune checkpoint inhibitors (ICIs) anti-PD-1 and anti-CTLA-4 for advanced melanoma, only 26%-52% of patients respond, and many experience grade III/IV immune-related adverse events. Motivated by the need for an effective therapy for patients non-responsive to clinically approved ICIs, we have developed a novel nanoimmunotherapy that combines locally administered Prussian blue nanoparticle-based photothermal therapy (PBNP-PTT) with systemically administered agonistic anti-CD137 monoclonal antibody therapy (aCD137). PBNP-PTT was administered at various thermal doses to melanoma cells , and was combined with aCD137 to test treatment effects on melanoma tumor progression, animal survival, immunological protection against tumor rechallenge, and hepatotoxicity.

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Japanese Black (Wagyu) cattle produce high-quality beef. However, whether Wagyu steers can be profitably raised under conditions different than the traditional Japanese ones remains unclear. From 2018 to 2020, we raised 262 Wagyu purebred steers, 103 Wagyu-by-Angus (Wangus) crossbred steers, and 43 Angus-by-European (ACL) crossbred steers on a Spanish farm with high welfare standards and a locally sourced, high-olein diet.

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Ammonia is an important pollutant emitted by broiler litter that can accumulate inside farms, impairing animal health and welfare productivity. An experiment was designed to evaluate of precision husbandry practices such as the effect of ventilation, animal density and growth rate as management options to reduce the adverse effects of ammonia exposure on productive parameters in broiler houses. Two identical experimental rooms were used in this study.

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Multiple ovulation and embryo transfer (MOET) systems have been intensively implemented in Japanese Black cattle in Japan and to create Japanese Black herds out of these areas. Environmental conditions influence MOET efficiency. Thus, we describe results of 137 in vivo, non-surgical embryo flushings performed between 2016-2020, in a full-blood Japanese Black herd kept in Spain and the possible effects of heat, year, bull, donor genetic value, and metabolic condition.

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Melanoma is the least common but deadliest type of skin cancer. Melanomagenesis is driven by a series of mutations and epigenetic alterations in oncogenes and tumor suppressor genes that allow melanomas to grow, evolve, and metastasize. Epigenetic alterations can also lead to immune evasion and development of resistance to therapies.

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