A small-molecule degrader of TET3 as treatment for anorexia nervosa in an animal model.

Anorexia nervosa (AN) is a psychiatric illness with the highest mortality. Current treatment options have been limited to psychotherapy and nutritional support, with low efficacy and high relapse rates. Hypothalamic AgRP (agouti-related peptide) neurons that coexpress AGRP and neuropeptide Y (NPY) play a critical role in driving feeding while also modulating other complex behaviors. We have previously reported that genetic ablation of Tet3, which encodes a member of the TET family dioxygenases, specifically in AgRP neurons in mice, activates these neurons and increases the expression of AGRP, NPY, and the vesicular GABA transporter (VGAT), leading to hyperphagia and anxiolytic effects. Bobcat339 is a synthetic small molecule predicted to bind to the catalytic pockets of TET proteins. Here, we report that Bobcat339 is effective in mitigating AN and anxiety/depressive-like behaviors using a well-established mouse model of activity-based anorexia (ABA). We show that treating mice with Bobcat339 decreases TET3 expression in AgRP neurons and activates these neurons leading to increased feeding, decreased compulsive running, and diminished lethality in the ABA model. Mechanistically, Bobcat339 induces TET3 protein degradation while simultaneously stimulating the expression of AGRP, NPY, and VGAT in a TET3-dependent manner both in mouse and human neuronal cells, demonstrating a conserved, previously unsuspected mode of action of Bobcat339. Our findings suggest that Bobcat339 may potentially be a therapeutic for anorexia nervosa and stress-related disorders.

Effects of complementary spiritual therapy on stress, anxiety, burnout syndrome and hematological parameters of professionals in a public hospital: a randomized controlled trial.

OBJECTIVES: This randomized controlled trial evaluated the stress, anxiety, and burnout of professionals exposed to complementary spiritist therapy (CST), which consists in therapeutic resources as prayer, Spiritist passe, fluidic water and spiritual education or control. METHODS: Seventy-six professionals were randomized to CST or control: to maintain the routine for 5 weeks. The ISSL scale, anxiety and depression Beck's indices, Maslach instrument, subjective well-being and WHOQOL-BREF were used at baseline and five-week. Blood count and cytokine dosage were collected at baseline, one-week and five-week. Analysis using the intention to treat approach. RESULTS: The means of variation of stress (exhaustion phase) between baseline and five-week were -1.50 ± 3.31 in the CST and 0.72 ± 3.50 in the control (p=0.036), effect size for CST group was d=0.65, which is considered medium effect. CST showed decrease in emotional exhaustion and negative affects, and increase in lymphocytes, erythrocyte parameters and platelets between the baseline and five-week (p<0.05). Reduction in IL-1ß and increase in total lymphocyte count were observed with 2-3 sessions per week, but that does not maintain when the number of sessions is decreased. Participants receiving ≥7 sessions reduced emotional exhaustion, depersonalization and stress, and improved hematological parameters throughout the study (p<0.05). CONCLUSIONS: CST may be effective in reducing stress (exhaustion phase) compared to control. Higher frequency of interventions promotes better psychic state, evidenced by large effect size for emotional exhaustion in burnout, and improves hematological parameters of professionals.

TET3 epigenetically controls feeding and stress response behaviors via AGRP neurons.

The TET family of dioxygenases promote DNA demethylation by oxidizing 5-methylcytosine to 5-hydroxymethylcytosine (5hmC). Hypothalamic agouti-related peptide-expressing (AGRP-expressing) neurons play an essential role in driving feeding, while also modulating nonfeeding behaviors. Besides AGRP, these neurons produce neuropeptide Y (NPY) and the neurotransmitter GABA, which act in concert to stimulate food intake and decrease energy expenditure. Notably, AGRP, NPY, and GABA can also elicit anxiolytic effects. Here, we report that in adult mouse AGRP neurons, CRISPR-mediated genetic ablation of Tet3, not previously known to be involved in central control of appetite and metabolism, induced hyperphagia, obesity, and diabetes, in addition to a reduction of stress-like behaviors. TET3 deficiency activated AGRP neurons, simultaneously upregulated the expression of Agrp, Npy, and the vesicular GABA transporter Slc32a1, and impeded leptin signaling. In particular, we uncovered a dynamic association of TET3 with the Agrp promoter in response to leptin signaling, which induced 5hmC modification that was associated with a chromatin-modifying complex leading to transcription inhibition, and this regulation occurred in both the mouse models and human cells. Our results unmasked TET3 as a critical central regulator of appetite and energy metabolism and revealed its unexpected dual role in the control of feeding and other complex behaviors through AGRP neurons.

Application of physical exercise therapies in breast cancer survivors and their effects on the inflammatory profile: A narrative review.

BACKGROUND: One of the adverse effects of cancer treatments is the exacerbation of inflammation, which generates numerous limitations and contributes to the development of several comorbidities and the recurrence of cancer itself. Physical exercise (PE) has been proposed as an efficient complementary strategy to combat the inflammatory effects of oncological treatments and to prevent the development of comorbidities, but its adequate application in breast cancer survivors (BCS) requires the establishment of consensuses and practical recommendations. OBJECTIVE: This study aimed to review the randomized controlled trials that evaluated the influence of PE in the inflammatory profile of BCS. METHODS: The search for articles published between 1999 and 2020 was done in PsycINFO, PubMed, Cochrane, Science Direct, and Scopus databases. RESULTS: Current knowledge reveals the effectiveness of PE in the functional independence and health of BCS. Evidence of the capacity of PE to improve the inflammatory profile and the immune response in BCS has also been described. However, the heterogeneity of the studies regarding structural training variables, types of exercise, stages of intervention, and severity of the disease, still do not allow the establishment of precise guidelines for the prescription and progression of exercise to improve the inflammatory process in BCS. DISCUSSION: . This review suggests a possible strategy to be used in the assessment, training prescription, and rehabilitation of BCS, to support the development of new studies and the work of exercise professionals in the prescription and application of physical training to improve health and inflammatory status in BCS.

Religiosidade/espiritualidade, indicadores de saúde mental e parâmetros hematológicos de profissio-nais de enfermagem / Religiosity/spirituality, mental health indicators and hematologic parameters of nursing professionals / Religiosidad/espiritualidad, indicadores de salud mental y parámetros hematológicos de profesionales de enfermeiras

Objetivo:analisara relação entre Religiosidade e Espiritualidade,indicadores de saúde mental, parâmetros hematológicos e percepção dasaúde de profissionais deenfermagem.Método:estudo transversal com 53 funcionários. Utilizou-se Medida Multidimensional Breve de Religiosidade e Espiritualidade, Inventário Stress Lipp,Ansiedade e Depressão de Beck, Bem-Estar Subjetivo,hemograma e imunoglobulina A. Resultados:Dimensões Experiências Espirituais Diárias eAutoavaliação Global são os fatores commaior forçade relação com os índices de estresse, depressão e Bem-Estar em profissionais.Participação religiosa e comprometimento foramosfatores que influenciarammaiores valores de leucócitos,neutrófilose imunoglobulina A. Conclusão:os resultados identificaram relação entre Religiosidade e Espiritualidade, indicadores de saúde mental e parâmetros hematológicos. Profissionais de enfermagemmais religiosos e espiritualistas apresentam melhor saúde mental e maior imunidade, além de melhor percepção de saúde (AU).

Objective:to analyze the relationship between Religiosity and Spirituality, mental health indicators and haematological parameters of nurses. Method:cross-sectional study with 53 employees. It was used Brief Multidimensional Measure of Religiosity and Spirituality (BMMRS), Lipp Stress Inventory, Beck Anxiety and Depression and Subjective Wellbeing, hemogram and immunoglobulin A. Results:dimensions Daily Spiritual Experiences and Global Religiosity and Spirituality Self-evaluation are the factors that present greater strength of relation with the indices of stress, depression and Subjective Wellbeing in professionals. Religious participation and impairment were the factors that influenced higher leukocyte, neutrophil and immunoglobulin A values.Conclusion:the results identified a relation between Religiosity and Spirituality, mental health indicators and haematological parameters, demonstrating that more religious and spiritualist nurses have better mental health and immunity,as well as a better perception of health (AU).

Objetivo:analizar la relación entre Religiosidad y Espiritualidad, indicadores de salud mental y parámetros hematológicos de enfermeras. Método:estudio transversal con 53 empleados. Se utilizó Medida Multidimensional Breve de Religiosidad y Espiritualidad (BMMRS), Inventario Stress Lipp, Escalas de Ansiedad y Depresión Beck y Bienestar Subjetivo, cuestionario de clasificación de la salud,hemograma yinmunoglobulina A. Resultados:las dimensiones Experiencias Espirituales Diarias y Autoevaluación Global de Religiosidad y Espiritualidad son los factores que presentan mayor fuerza de relación con los índices de estrés, depresión y Bienestar Subjetivo en profesionales. La participación religiosa y compromiso fueron los principales factores que influyen en los valores de leucocitos, neutrófilos, y la inmunoglobulina A. Conclusión:los resultados identificaron relación entre R/E, indicadores de salud mental y parámetros hematológicos, demostrandoque enfermeras más religiosos y espiritualistas presentan mejor salud mental y mayor inmunidad, además de una mejor percepción de la salud (AU).

Metabolism: A Burning Opioid Issue in Obesity Therapeutics.

Food restriction triggers a lowering in body temperature. A new study now provides a mechanism for this process that relies on opioid signaling in the hypothalamus. These observations suggest potential new therapeutics for obesity.