Regulation of Inflammatory Reaction in Health and Disease.

Inflammation is a key mechanism for the clearance of infective agents and other inflammatory triggers and is pivotal for the repairing processes of the affected tissues. Inflammation is a multistep process driven by a great number of mediators which regulate specific aspects of the inflammatory response, in agreement with a well-defined chronobiological program. A great number of inflammation-related diseases show a deeply altered immune chronobiology (e.g., COVID-19-related cytokines storm). This aspect highlights the need for a deeper understanding of the inflammatory phenomenon. It is fundamental to study inflammation as a multilevel phenomenon. Of particular interest is the low-grade chronic inflammation, which is an etiological factor of many chronic diseases. Nowadays, the therapeutic approach to low grade chronic inflammation is one of the great challenges of traditional pharmacology. Currently, no drugs specifically designed for the treatment of chronic inflammatory forms are available. Today, bioregulatory systems medicine (BrSM) and low dose medicine (LDM), two pharmacological paradigms grounded in systems medicine, potentially represent new tools for the treatment of inflammation-related diseases. Scientific research has assessed the effectiveness and safety of both these therapeutic approaches, in particular for the management of chronic inflammatory conditions and chronic immunological dysregulations.

The short-term stress response - Mother nature's mechanism for enhancing protection and performance under conditions of threat, challenge, and opportunity.

Our group has proposed that in contrast to chronic stress that can have harmful effects, the short-term (fight-or-flight) stress response (lasting for minutes to hours) is nature's fundamental survival mechanism that enhances protection and performance under conditions involving threat/challenge/opportunity. Short-term stress enhances innate/primary, adaptive/secondary, vaccine-induced, and anti-tumor immune responses, and post-surgical recovery. Mechanisms and mediators include stress hormones, dendritic cell, neutrophil, macrophage, and lymphocyte trafficking/function and local/systemic chemokine and cytokine production. Short-term stress may also enhance mental/cognitive and physical performance through effects on brain, musculo-skeletal, and cardiovascular function, reappraisal of threat/anxiety, and training-induced stress-optimization. Therefore, short-term stress psychology/physiology could be harnessed to enhance immuno-protection, as well as mental and physical performance. This review aims to provide a conceptual framework and targets for further investigation of mechanisms and conditions under which the protective/adaptive aspects of short-term stress/exercise can be optimized/harnessed, and for developing pharmacological/biobehavioral interventions to enhance health/healing, and mental/cognitive/physical performance.

Integrative Oncology's 30-Year Anniversary: What Have We Achieved? A North American Naturopathic Oncology Perspective.

In 1991 the U.S. Congress mandated that the National Institutes of Health (NIH) form the Office of Alternative Medicine to study alternative medical therapies, especially in oncology care. Shortly after, the National Cancer Institute (NCI) created its own division of complementary and alternative medicine (Office of Complementary and Alternative Medicine). At the genesis of the field 30 years ago, what were we hoping to see accomplished by now? In this article we take a look back at milestones, shortfalls and future directions. Exciting opportunities exist to direct our established subspeciality's future directions and we have made valuable advances the field of integrative oncology over the last 30 years: 1, IV high dose ascorbate has clinical research-based applications when used concurrently with some chemotherapeutic agents. 2. Whole body, extracorporeal and locoregional hyperthermia are being applied in treating solid tumors, including brain tumors. 3. PDL-1 tumor microenvironment testing and PDL-1 inhibitor immunotherapies have surprisingly excellent outcomes in a subgroup of cancer patients. 4. Tumor DNA sequencing (resected tumor and circulating tumor DNA in blood) has led to personalized precision targeted treatments. 5. Glucose metabolism's role in cancer progression is better understood and better therapies are available (e.g., intermittent fasting, metformin). 6. Medical cannabis has a larger role in treating chemotherapy-related side effects and shows promise for anti-proliferative effects. 8. Greater understanding has been gained of the interdependence and mutual regulation of processes in psychoneuroendocrinoimmunology (PNEI). The burgeoning field of PNEI has exponentially expanded the discussion of tumorigenesis, apoptosis, and introduced to the field the investigation of more holistic approaches to immune regulation and cancer care. 8. Psychedelic-assisted psychotherapy is gaining traction especially for cancer patients facing demoralization, existential and spiritual distress, anxiety, depression and trauma related to the diagnosis and treatment of their cancer. 9. Spiritual health of cancer patients is more commonly addressed and measurable with an NIH validated scale. 10. Mind-Body therapies are efficacious for reducing cancer-related distress and are included in many cancer care programs.

The Role of the Stress Response in Metabolic Dysfunction-Associated Fatty Liver Disease: A Psychoneuroendocrineimmunology-Based Perspective.

The novel term metabolic dysfunction-associated fatty liver disease (MAFLD), which has been proposed to describe the major cause of hepatic disease, pinpoints the coexistence of multiple metabolic disturbances and liver steatosis, giving rise to different phenotypic manifestations. Within the psychoneuroendocrineimmunological (PNEI) network that regulates body-mind interactions, the stress response plays a pervasive role by affecting metabolic, hormonal, immune, and behavioral balance. In this perspective, we focus on chronic psychosocial stress and high levels of cortisol to highlight their role in MAFLD pathogenesis and worsening. From a PNEI perspective, considering the stress response as a therapeutic target in MAFLD allows for simultaneously influencing multiple pathways in the development of MAFLD, including dysmetabolism, inflammation, feeding behaviors, gut-liver axis, and dysbiosis, with the hope of better outcomes.

Online Questionnaire with Fibromyalgia Patients Reveals Correlations among Type of Pain, Psychological Alterations, and Effectiveness of Non-Pharmacological Therapies.

Fibromyalgia (FM) is a chronic pain syndrome with an unclear etiology. In addition to pain, FM patients suffer from a diverse array of symptoms and comorbidities, encompassing fatigue, cognitive dysfunction, mood disorders, sleep deprivation, and dizziness. Due to the complexity of FM, the diagnosis and treatment of it are highly challenging. The aim of the present work was to investigate some clinical and psychological characteristics of FM patients, and to uncover possible correlations with pharmacological and non-pharmacological therapies. We conducted a cross-sectional, questionnaire-based study aimed at evaluating pain, psychological traits, and the self-perceived effectiveness of pharmacological and non-pharmacological treatments in an Italian population of FM patients. Descriptive statistics, correlation, and inference analyses were performed. We found a prevalence of a neuropathic/nociplastic type of pain, which correlated with psychological traits such as anxiety, low mood, psychophysical discomfort, and the inability to relax. The pain type and psychological traits proved to play a role in determining the self-perceived effectiveness of therapeutic interventions. Patients revealed a better response to non-pharmacological therapies, particularly dietary interventions, relaxation techniques, and psychotherapy rather than pharmacological interventions. The sum of our data indicates that for better outcomes, the type of pain and psychological traits should be considered for tailor-made treatments considering non-pharmacological protocols as a complement to the use of drugs.

Aging in the Perspective of Integrative Medicine, Psychoneuroendocrineimmunology and Hormesis.

Aging has been considered a progressive decrease of a living organism's homeodynamics, which indicates a reduction of psycho-biological resilience. This narrative review provides an overview of the available literature related to the holistic approach of integrative medicine, Psychoneuroendocrineimmunology (PNEI) and hormesis in the aging process. On the basis of Pathophysiology of cell senescence and of chronic degenerative diseases, possible preventive/therapeutic pathways have been examined. Chronic low grade cellular inflammation and chronic stress have been shown as the general interlinked factors inducing aging, on the basis of complex biochemical, cell and multi-organ derangements. The main cell degenerative processes which have been related to aging are: altered mitochondria DNA/metabolism, excessive oxidative stress, glycation, alteration of autophagy and proteasome, and genome alterations. Literature about longevity-targeting interventions, beyond conventional medicine, describes a spectrum of possible measures to improve psycho-biological resilience, based on the PNEI paradigm, on hormesis and upon mitochondriatargeted interventions. Calorie restriction, exercising, fasting, nutraceuticals, sleep regulation, specific breathing, meditation and psychotherapy are discussed, among others.

Stress and the psyche-brain-immune network in psychiatric diseases based on psychoneuroendocrineimmunology: a concise review.

In the last decades, psychoneuroendocrineimmunology research has made relevant contributions to the fields of neuroscience, psychobiology, epigenetics, molecular biology, and clinical research by studying the effect of stress on human health and highlighting the close interrelations between psyche, brain, and bodily systems. It is now well recognized that chronic stress can alter the physiological cross-talk between brain and biological systems, leading to long-lasting maladaptive effects (allostatic overload) on the nervous, immune, endocrine, and metabolic systems, which compromises stress resiliency and health. Stressful conditions in early life have been associated with profound alterations in cortical and subcortical brain regions involved in emotion regulation and the salience network, showing relevant overlap with different psychiatric conditions. This paper provides a summary of the available literature concerning the notable effects of stress on the brain and immune system. We highlight the role of epigenetics as a mechanistic pathway mediating the influences of the social and physical environment on brain structure and connectivity, the immune system, and psycho-physical health in psychiatric diseases. We also summarize the evidence regarding the effects of stress management techniques (mainly psychotherapy and meditation practice) on clinical outcomes, brain neurocircuitry, and immune-inflammatory network in major psychiatric diseases.

Stress and Inflammation in Coronary Artery Disease: A Review Psychoneuroendocrineimmunology-Based.

Recent findings have deeply changed the current view of coronary heart disease, going beyond the simplistic model of atherosclerosis as a passive process involving cholesterol build-up in the subintimal space of the arteries until their final occlusion and/or thrombosis and instead focusing on the key roles of inflammation and the immune system in plaque formation and destabilization. Chronic inflammation is a typical hallmark of cardiac disease, worsening outcomes irrespective of serum cholesterol levels. Low-grade chronic inflammation correlates with higher incidence of several non-cardiac diseases, including depression, and chronic depression is now listed among the most important cardiovascular risk factors for poor prognosis among patients with myocardial infarction. In this review, we include recent evidence describing the immune and endocrine properties of the heart and their critical roles in acute ischaemic damage and in post-infarct myocardial remodeling. The importance of the central and autonomic regulation of cardiac functions, namely, the neuro-cardiac axis, is extensively explained, highlighting the roles of acute and chronic stress, circadian rhythms, emotions and the social environment in triggering acute cardiac events and worsening heart function and metabolism in chronic cardiovascular diseases. We have also included specific sections related to stress-induced myocardial ischaemia measurements and stress cardiomyopathy. The complex network of reciprocal interconnections between the heart and the main biological systems we have presented in this paper provides a new vision of cardiovascular science based on psychoneuroendocrineimmunology.

Estrés, psiconeuroendocrinoinmunología y enfermedades reumatológicas. Actualización del tema / Stress, Psychoneuroendocrinoimmunology and rheumatological diseases. Actualization of this topic

El estrés se define como el estado de alarma de los organismos ante diversos desafíos. La Psiconeuroendocrinoinmunología es una ciencia que integra la psiquis, el sistema nervioso, endocrino e inmune; y estudia las múltiples y complejas interrelaciones entre ellos lo cual permite tratar de manera integral el proceso salud-enfermedad. La alteración del equilibrio entre la psiquis y los sistemas mencionados puede ocasionar daños al organismo como es el caso de algunas enfermedades reumatológicas(AU)

Stress is defined as the state of alarm of living beings in case of various challenges. Psycho-neuro-endocrine-immunology is a science that integrates the psyche with the nervous, endocrine and immune systems. It studies the multiple and complex interrelations among them, which allows us to deal comprehensively with the health-disease process. The alteration if the balance between the psyche and the aforementioned systems can cause damage to the organism, as in the case of some rheumatologic diseases(AU)

Aromaterapia e yogaterapia no climatério: Os efeitos de aromaterapia e yogaterapia na qualidade de vida, nos níveis de stress e na intensidade e frequência de fogacho em mulheres na fase do climatério / Aromatherapy and yogatherapy in climacterium: the effects of aromatherapy and yogatherapy on quality of life, stress levels and intensity and frequence of hot flashes in climacteric women

INTRODUCAO: Os sintomas de climaterio podem perturbar intensamente a vida, sendo o fogacho o sintoma de maior incidencia. Aromaterapia e yogaterapia podem oferecer tratamentos eficazes para sintomas de climaterio, em especial o fogacho, por apresentarem mecanismos terapeuticos semelhantes ao eixo fisiologico do fogacho. OBJETIVO PRINCIPAL: Verificar e analisar os desfechos clinicos fisiologicos e psicologicos da aromaterapia olfativa e de exercicios respiratorios de yogaterapia, associados e individualmente, na qualidade de vida, nos niveis de stress subjetivo e na intensidade e frequencia do fogacho de mulheres na fase do climaterio. METODO: Foram avaliadas 85 mulheres na fase do climaterio, das quais 64 participaram da Fase 1 (somente avaliacao) do estudo e 34 participaram da Fase 2 (tratamento). A coleta foi realizada no CEPE-USP. O estudo consiste de um ensaio clinico pragmatico com randomizacao restrita, controlado por grupo controle e placebo, duplo-cego, com intervencao baseada no modelo psiconeuroendocrinoimunologico. Foram realizados tratamentos com inalacao de sinergia aromaterapeutica com ou sem exercicios respiratorios de yogaterapia, durante 12 semanas, duas vezes por semana em sessoes de uma hora. O estudo foi aprovado pelo Comite de Etica em Pesquisa da Escola de Educacao Fisica e Esporte da Universidade de Sao Paulo e foi inscrito no clinicaltrials.gov. RESULTADOS E DISCUSSAO: Os resultados da pesquisa mostraram melhora estatisticamente significante dos sintomas de climaterio para os tres grupos de intervencao. Houve diminuicao significativa do sintoma de fogacho, assim como da queixa de fogacho, sendo que o fogacho foi eliminado em cinco sujeitos. A intensidade e a frequencia de fogacho diminuiram em todos os grupos de intervencao e se mantiveram constantes no grupo controle. O tratamento proposto de aromaterapia se mostrou mais eficaz do que o tratamento proposto de yogaterapia na diminuicao do sintoma de fogacho, quando esses tratamentos eram aplicados isoladamente. A associacao das duas terapias se mostrou benefica, aumentando a eficacia e intensificando a melhora do sintoma de fogacho. Os efeitos globais dos tratamentos variaram intensamente quanto aos outros dominios de sintomas do climaterio. A melhora dos sintomas vasomotores do climaterio (fogacho e suor noturno), foi acompanhada de melhora significativa nos niveis de stress subjetivo, na qualidade do sono e da qualidade de vida em todos os grupos de intervencao. Esse trabalho tambem permitiu discussoes secundarias sobre o climaterio e as terapias, permitindo a sua compreensao a partir do modelo psiconeuroendocrinoimunologico. CONCLUSAO: Esse estudo serviu como um delineamento geral dos sintomas de climaterio, da aromaterapia e da yogaterapia a partir do modelo psiconeuroendocrinoimunologico. Os resultados apresentados nao podem ser generalizados para a populacao por causa da amostra pequena, mas podem indicar os resultados mais promissores e, com isso, esse trabalho pode ser o ponto de partida para novos estudos, auxiliando na elaboracao de questoes de pesquisa claras e metodos de pesquisa adequados para estuda-las.(AU)

INTRODUCTION: Climacteric symptoms can disturb life considerably. Hot flashes are the symptom with highest incidence. Aromatherapy and yogatherapy can offer efficient treatments for climacteric symptoms, specially hot flashes, because their therapeutic mechanisms are similar to the physiological mechanism of hot flashes. MAIN OBJECTIVE: To analyze the psychological and physiological clinical outcomes of olfactory aromatherapy and breathing exercises of yogatherapy, associated or individually, on the quality of life, subjective stress levels and intensity and frequency of hot flashes in women in the climacteric period. METHODS: 85 women in the climacteric period were evaluated, 64 of these subjects participated in Phase 1 (assessment) and 34 participated in Phase 2 (treatment) . Data collection was performed at CEPE-USP. The study consists of a doubleblind, pragmatic clinical trial with restricted randomization, controlled by control and placebo groups. The intervention was based on the psychoneuroendocrineimmunological model. Treatments were performed with inhalation of an aromatherapeutic synergy developed for the study with or without yogatherapy breathing exercises for 12 weeks, twice per week in one hour sessions. The study was approved by the ethics comitte Comite de Etica em Pesquisa da Escola de Educacao Fisica e Esporte da Universidade de Sao Paulo and was registered in clinicaltrials.gov. RESULTS AND DISCUSSION: The results showed statistically significant improvement in symptoms of menopause for the three intervention groups. There was significant decrease in symptom of hot flashes, as well as complaints of hot flashes and this symptom was eliminated in five subjects. The intensity and frequency of hot flashes decreased in all intervention groups and remained constant in the control group. Aromatherapy was more effective than yogatherapy to decrease the symptoms of hot flashes, when these treatments were applied separately. The combination of the two therapies proved beneficial, increasing the effectiveness and enhancing the improvement of the symptom of hot flashes. The overall effects of the treatments varied intensely for other climacteric symptoms. The improvement of vasomotor symptoms of menopause (hot flashes and night sweats), was accompanied by a significant improvement in stress levels, quality of sleep and quality of life in all intervention groups. This research also permitted secondary discussions about climacterium and the therapies, permiting their understanding through the psychoneuroendocrineimmunological model. CONCLUSION: This study served as a general outline of climacteric symptoms, aromatherapy and yogatherapy through the psychoneuroendocrineimmunological model. The results cannot be generalized to the population because of the small sample size. However, the most promissing results can be indicated and this research can be the starting point for further studies, assisting in the preparation of clear research questions and suitable research methods to study them .(AU)

Aromaterapia e yogaterapia no climatério: os efeitos de aromaterapia e yogaterapia na qualidade de vida, nos níveis de stress e na intensidade e frequência de fogacho em mulheres na fase do climatério / Aromatherapy and yogatherapy in climacterium: the effects of aromatherapy and yogatherapy on quality of life, stress levels and intensity and frequence of hot flashes in climacteric women

INTRODUCAO: Os sintomas de climaterio podem perturbar intensamente a vida, sendo o fogacho o sintoma de maior incidencia. Aromaterapia e yogaterapia podem oferecer tratamentos eficazes para sintomas de climaterio, em especial o fogacho, por apresentarem mecanismos terapeuticos semelhantes ao eixo fisiologico do fogacho. OBJETIVO PRINCIPAL: Verificar e analisar os desfechos clinicos fisiologicos e psicologicos da aromaterapia olfativa e de exercicios respiratorios de yogaterapia, associados e individualmente, na qualidade de vida, nos niveis de stress subjetivo e na intensidade e frequencia do fogacho de mulheres na fase do climaterio. METODO: Foram avaliadas 85 mulheres na fase do climaterio, das quais 64 participaram da Fase 1 (somente avaliacao) do estudo e 34 participaram da Fase 2 (tratamento). A coleta foi realizada no CEPE-USP. O estudo consiste de um ensaio clinico pragmatico com randomizacao restrita, controlado por grupo controle e placebo, duplo-cego, com intervencao baseada no modelo psiconeuroendocrinoimunologico. Foram realizados tratamentos com inalacao de sinergia aromaterapeutica com ou sem exercicios respiratorios de yogaterapia, durante 12 semanas, duas vezes por semana em sessoes de uma hora. O estudo foi aprovado pelo Comite de Etica em Pesquisa da Escola de Educacao Fisica e Esporte da Universidade de Sao Paulo e foi inscrito no clinicaltrials.gov. RESULTADOS E DISCUSSAO: Os resultados da pesquisa mostraram melhora estatisticamente significante dos sintomas de climaterio para os tres grupos de intervencao. Houve diminuicao significativa do sintoma de fogacho, assim como da queixa de fogacho, sendo que o fogacho foi eliminado em cinco sujeitos.(AU)

INTRODUCTION: Climacteric symptoms can disturb life considerably. Hot flashes are the symptom with highest incidence. Aromatherapy and yogatherapy can offer efficient treatments for climacteric symptoms, specially hot flashes, because their therapeutic mechanisms are similar to the physiological mechanism of hot flashes. MAIN OBJECTIVE: To analyze the psychological and physiological clinical outcomes of olfactory aromatherapy and breathing exercises of yogatherapy, associated or individually, on the quality of life, subjective stress levels and intensity and frequency of hot flashes in women in the climacteric period. METHODS: 85 women in the climacteric period were evaluated, 64 of these subjects participated in Phase 1 (assessment) and 34 participated in Phase 2 (treatment) . Data collection was performed at CEPE-USP. The study consists of a doubleblind, pragmatic clinical trial with restricted randomization, controlled by control and placebo groups. The intervention was based on the psychoneuroendocrineimmunological model. Treatments were performed with inhalation of an aromatherapeutic synergy developed for the study with or without yogatherapy breathing exercises for 12 weeks, twice per week in one hour sessions. The study was approved by the ethics comitte Comite de Etica em Pesquisa da Escola de Educacao Fisica e Esporte da Universidade de Sao Paulo and was registered in clinicaltrials.gov. RESULTS AND DISCUSSION: The results showed statistically significant improvement in symptoms of menopause for the three intervention groups. There was significant decrease in symptom of hot flashes, as well as complaints of hot flashes and this symptom was eliminated in five subjects.(AU)