The Involvement of Polyunsaturated Fatty Acids in Apoptosis Mechanisms and Their Implications in Cancer.

Cancer is a significant global public health issue and, despite advancements in detection and treatment, the prognosis remains poor. Cancer is a complex disease characterized by various hallmarks, including dysregulation in apoptotic cell death pathways. Apoptosis is a programmed cell death process that efficiently eliminates damaged cells. Several studies have indicated the involvement of polyunsaturated fatty acids (PUFAs) in apoptosis, including omega-3 PUFAs such as alpha-linolenic acid, docosahexaenoic acid, and eicosapentaenoic acid. However, the role of omega-6 PUFAs, such as linoleic acid, gamma-linolenic acid, and arachidonic acid, in apoptosis is controversial, with some studies supporting their activation of apoptosis and others suggesting inhibition. These PUFAs are essential fatty acids, and Western populations today have a high consumption rate of omega-6 to omega-3 PUFAs. This review focuses on presenting the diverse molecular mechanisms evidence in both in vitro and in vivo models, to help clarify the controversial involvement of omega-3 and omega-6 PUFAs in apoptosis mechanisms in cancer.

Influencia de la musicoterapia en la disminución de cifras tensionales moderadamente altas

Fundamento la hipertensión arterial es una enfermedad con alta prevalencia a nivel mundial. Entre las alternativas para su tratamiento, la musicoterapia resulta eficaz junto al tratamiento farmacológico. Objetivo describir la influencia de la musicoterapia en la disminución de cifras tensionales moderadamente altas. Métodos se realizó un estudio observacional, analítico, de casos y controles, con pacientes (n=100) que acudieron al Cuerpo de guardia del Policlínico Rolando Ricardo Estrada, del municipio de Báguanos (Holguín), en el período 2021-2022, seleccionados mediante un muestreo no probabilístico intencional. Fueron creados dos grupos de 50 pacientes cada uno. El grupo de casos fue expuesto a la musicoterapia, no así el de control. Resultados en ambos grupos predominaron los pacientes con edades entre 40 y 59 años (41 %), del sexo femenino (55 %) y con diagnóstico previo de hipertensión arterial (58 %). En el momento de acudir al policlínico, en los dos grupos predominó la presión sistólica entre 140 y 159 mmHg (62 %). Luego de haber transcurrido una hora, en la mayoría de los pacientes del grupo de casos las cifras bajaron hasta 120 y 139 mmHg (32 %). En el grupo control se evidenció una leve disminución, pero se mantuvo mayor porcentaje de pacientes con 140 a 159 mmHg (25 %). Conclusión los pacientes expuestos a la musicoterapia evidenciaron una disminución más marcada de las cifras tensionales moderadamente elevadas, en comparación con los no expuestos.

Background arterial hypertension is a disease with a high prevalence worldwide. Among the alternatives for its treatment, music therapy is effective together with pharmacological treatment. Objective to describe the music therapy influence in the reduction of moderately high blood pressure figures. Methods an observational, analytical, case-control study was carried out with patients (n=100) who attended the Rolando Ricardo Estrada Polyclinic's Emergency Room, in the Báguanos municipality (Holguín), from 2021 to 2022, selected through purposive non- probabilistic sampling. Two groups of 50 patients each were created. The case group was exposed to music therapy, but not the control group. Results in both groups, patients aged between 40 and 59 years (41%), female (55%) and with a previous diagnosis of arterial hypertension (58%) predominated. At the time of going to the polyclinic, systolic pressure between 140 and 159 mmHg (62%) predominated in both groups. After one hour had elapsed, in most of the patients in the case group the figures dropped to 120 and 139 mmHg (32%). In the control group, a slight decrease was observed, but a higher percentage of patients with 140 to 159 mmHg (25%) remained. Conclusion patients exposed to music therapy showed a more marked decrease in moderately elevated blood pressure figures, compared to those not exposed.

Omega-6 Polyunsaturated Fatty Acids Enhance Tumor Aggressiveness in Experimental Lung Cancer Model: Important Role of Oxylipins.

Lung cancer is currently the leading cause of cancer death worldwide; it is often diagnosed at an advanced stage and bears poor prognosis. It has been shown that diet is an important environmental factor that contributes to the risk and mortality of several types of cancers. Intake of ω-3 and ω-6 PUFAs plays an important role in cancer risk and progression. Current Western populations have high consumption of ω-6 PUFAs with a ratio of ω-6/ω-3 PUFAs at 15:1 to 16.7:1 This high consumption of ω-6 PUFAs is related to increased cancer risk and progression. However, whether a diet rich in ω-6 PUFAs can contribute to tumor aggressiveness has not been well investigated. We used a murine model of pulmonary squamous cell carcinoma to study the aggressiveness of tumors in mice fed with a diet rich in ω-6 PUFAs and its relationship with oxylipins. Our results shown that the mice fed a diet rich in ω-6 showed a marked increase in proliferation, angiogenesis and pro-inflammatory markers and decreased expression of pro-apoptotic proteins in their tumors. Oxylipin profiling revealed an upregulation of various pro-tumoral oxylipins including PGs, HETEs, DiHETrEs and HODEs. These results demonstrate for the first time that high intake of ω-6 PUFAs in the diet enhances the malignancy of tumor cells by histological changes on tumor dedifferentiation and increases cell proliferation, angiogenesis, pro-inflammatory oxylipins and molecular aggressiveness targets such as NF-κB p65, YY1, COX-2 and TGF-ß.

Experience with ambulatory high-dose methotrexate administration as CNS prophylaxis in patients with non-Hodgkin lymphoma.

BACKGROUND: We describe the feasibility and safety of an oral administration schedule of hydration, alkalinization and leucovorin rescue with an ambulatory high-dose methotrexate regimen. METHODS: Single-centre prospective observational study conducted within a tertiary hospital where all patients have received systemic high-dose methotrexate (3.5 g/m2). Patients were instructed to keep an adequate ambulatory oral hydration and alkalinization to monitor urine pH and to adjust bicarbonate according to our institution's treatment protocol. High-dose methotrexate was infused over 4 h. Urine pH was checked before high-dose methotrexate administration, and for any value less than 7 a sodium bicarbonate bolus was given. Leucovorin at a standard dose was begun 24 h after high-dose methotrexate. methotrexate serum concentrations were monitored daily from 24 h after administration until clearance (level ≤ 0.1 µmol/L). RESULTS: From January 2016 to June 2018, 49 ambulatory high-dose methotrexate courses were given to 18 patients. No dose reduction was required afterwards. All patients completed succesfully the planned three doses in an outpatient basis, except four patients, one of them due to pneumonitis. Previous to methotrexate infusion, urinary pH > 7 was achieved in 35 (79.5%) cycles. Methotrexate clearance was achieved by 72 h in 35 courses (71.4%), and by 96 h in 100%. Neutropenia/trombocytopenia grades III/IV were observed in four cycles (8.16%) and two (4.08%) cycles, respectively. Around 20.40% were associated with stomatitis, 14.20% vomiting, 10.20% asthenia, 8.16% diarrhea and 6.12% with renal toxicity. CONCLUSIONS: Ambulatory administration of high-dose methotrexate as CNS prophylaxis is safe and feasible following the described approach, allowing us to optimize healthcare resources.

Role of Yin Yang-1 (YY1) in the transcription regulation of the multi-drug resistance (MDR1) gene.

Resistance to chemotherapy hinders the successful treatment of acute lymphoblastic leukemia (ALL). The multi-drug resistance-1 (MDR1/ABCB1) gene encodes P-glycoprotein (P-gp), which plays an important role in chemoresistance; however, its transcriptional regulation remains unclear. We investigated the role of YY1 in the regulation of MDR1 and its relation to ALL outcomes. Analysis of the MDR1 promoter revealed four putative YY1-binding sites, which we analyzed using a reporter system and ChIP analysis. YY1 silencing resulted in the inhibition of MDR1 expression and function. The clinical roles of YY1 and MDR1 expression were evaluated in children with ALL. Expression of both proteins was increased in ALL patients compared to controls. We identified a positive correlation between YY1 and MDR1 expression. High levels of YY1 were associated with decreased overall survival. Our results demonstrated that YY1 regulates the transcription of MDR1. Therefore, YY1 may serve as a useful prognostic and/or therapeutic target.

Letters from relatives: a source of information providing rich insight into the experience of the family in palliative care.

Studies on the effectiveness and efficiency of palliative care (PC) services that use a methodology similar to that used by studies in other medical specialties face serious limitations, since the goals of PC are substantially different. Qualitative research methods can make an important contribution to our understanding of the features of palliative care (PC) that are most relevant to patients and their relatives. The goal of this study was to understand the reasons behind the gratitude shown in letters from bereaved relatives sent to two PC units, one in Spain and one in Portugal. A thematic analysis of the content of the letters was independently carried out by three researchers, who later collaborated to write up the results. Relatives appeared grateful primarily for the humane attitude, professional treatment, and emotional support that their loved ones received from the PC team; they thanked the team for creating a special atmosphere and offering holistic care, and they talked about the contrast between PC and other forms of care. The unsolicited gratitude expressed in their letters constitutes a valid and particularly rich source of information about the contribution that a PC team can make.