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.
View Article and Find Full Text PDFBackground: 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.
View Article and Find Full Text PDFThe 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.
View Article and Find Full Text PDFWe 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.
View Article and Find Full Text PDFNon-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.
View Article and Find Full Text PDFColorectal 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.
View Article and Find Full Text PDFAims: 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.
View Article and Find Full Text PDFIntroduction: 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.
View Article and Find Full Text PDFProgesterone (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).
View Article and Find Full Text PDFA 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.
View Article and Find Full Text PDFTo 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.
View Article and Find Full Text PDFPurpose: 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.
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.
View Article and Find Full Text PDFDespite 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.
View Article and Find Full Text PDFJapanese 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.
View Article and Find Full Text PDFAmmonia 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.
View Article and Find Full Text PDFMultiple 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.
View Article and Find Full Text PDFMelanoma 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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