Trilobolide-6-O-isobutyrate from Sphagneticola trilobata acts by inducing oxidative stress, metabolic changes and apoptosis-like processes by caspase 3/7 activation of human lung cancer cell lines.

BACKGROUND: Lung cancer, a chronic and heterogeneous disease, is the leading cause of cancer-related death on a global scale. Presently, despite a variety of available treatments, their effectiveness is limited, often resulting in considerable toxicity and adverse effects. Additionally, the development of chemoresistance in cancer cells poses a challenge. Trilobolide-6-O-isobutyrate (TBB), a natural sesquiterpene lactone extracted from Sphagneticola trilobata, has exhibited antitumor effects. Its pharmacological properties in NSCLC lung cancer, however, have not been explored. PURPOSE: This study evaluated the impact of TBB on the A549 and NCI-H460 tumor cell lines in vitro, examining its antiproliferative properties and initial mechanisms of cell death. METHODS: TBB, obtained at 98 % purity from S. trilobata leaves, was characterized using chromatographic techniques. Subsequently, its impact on inhibiting tumor cell proliferation in vitro, TBB-induced cytotoxicity in LLC-MK2, THP-1, AMJ2-C11 cells, as well as its effects on sheep erythrocytes, and the underlying mechanisms of cell death, were assessed. RESULTS: In silico predictions have shown promising drug-likeness potential for TBB, indicating high oral bioavailability and intestinal absorption. Treatment of A549 and NCI-H460 human tumor cells with TBB demonstrated a direct impact, inducing significant morphological and structural alterations. TBB also reduced migratory capacity without causing toxicity at lower concentrations to LLC-MK2, THP-1 and AMJ2-C11 cell lines. This antiproliferative effect correlated with elevated oxidative stress, characterized by increased levels of ROS, superoxide anion radicals and NO, accompanied by a decrease in antioxidant markers: SOD and GSH. TBB-stress-induced led to changes in cell metabolism, fostering the accumulation of lipid droplets and autophagic vacuoles. Stress also resulted in compromised mitochondrial integrity, a crucial aspect of cellular function. Additionally, TBB prompted apoptosis-like cell death through activation of caspase 3/7 stressors. CONCLUSION: These findings underscore the potential of TBB as a promising candidate for future studies and suggest its viability as an additional component in the development of novel anticancer drugs prototypes.

Role of Inflammatory Mechanisms in Major Depressive Disorder: From Etiology to Potential Pharmacological Targets.

The involvement of central and peripheral inflammation in the pathogenesis and prognosis of major depressive disorder (MDD) has been demonstrated. The increase of pro-inflammatory cytokines (interleukin (IL)-1ß, IL-6, IL-18, and TNF-α) in individuals with depression may elicit neuroinflammatory processes and peripheral inflammation, mechanisms that, in turn, can contribute to gut microbiota dysbiosis. Together, neuroinflammation and gut dysbiosis induce alterations in tryptophan metabolism, culminating in decreased serotonin synthesis, impairments in neuroplasticity-related mechanisms, and glutamate-mediated excitotoxicity. This review aims to highlight the inflammatory mechanisms (neuroinflammation, peripheral inflammation, and gut dysbiosis) involved in the pathophysiology of MDD and to explore novel anti-inflammatory therapeutic approaches for this psychiatric disturbance. Several lines of evidence have indicated that in addition to antidepressants, physical exercise, probiotics, and nutraceuticals (agmatine, ascorbic acid, and vitamin D) possess anti-inflammatory effects that may contribute to their antidepressant properties. Further studies are necessary to explore the therapeutic benefits of these alternative therapies for MDD.

Do spirituality and emotional intelligence improve the perception of the ability to provide care at the end of life? The role of knowledge and self-efficacy.

OBJECTIVES: Spirituality, emotional intelligence, and palliative care (PC) knowledge have a positive and direct influence on self-efficacy and on perception of preparation and ability to provide end-of-life (EOL) care. The aim of this work is to propose a conceptual model that relates spirituality, emotional intelligence, PC knowledge, self-efficacy, and the preparation and ability to provide EOL care by doctors and nurses. METHODS: Quantitative, exploratory, descriptive, and inferential study applied to doctors and nurses in a hospital in the north of Portugal, between May and July 2022. The data collection instrument includes a questionnaire. The relationships between latent variables were evaluated using structural equation models by the partial least squares method using the Smart PLS 3.0 software. It was obtained the previous authorization of the ethics committee. RESULTS: The results (n = 380) indicate that self-efficacy, spirituality, and PC knowledge have a positive influence on the ability to provide EOL care. Emotional intelligence and spirituality have a direct and positive effect on self-efficacy. There is no direct influence of emotional intelligence on the ability to provide EOL care, but emotional intelligence has an indirect effect mediated by self-efficacy. SIGNIFICANCE OF RESULTS: Spirituality, self-efficacy, and emotional intelligence are very important for the ability of doctors and nurses to provide EOL care. The identification of predictive factors of the ability to provide EOL care and the determination of the relationship between them can improve the provision of EOL care, reduction of health costs, timely and early referral of people to PC, and increase life quality.

Chemical Characterization, Phenolic Compounds Quantification, and Assessment of Antioxidant and Anti-Acetylcholinesterase Activities of Byrsonima sericea DC fruits.

Byrsonima sericea is a species native to Brazil that is widely used in traditional medicine. The seed ethanol extract (SEE) had the highest content of total phenols (179.35 mg GAE g-1 extract) and flavonoids (10.42 mg QE g-1 extract) and was the most active in relation to antioxidant activity (DPPH: IC50 =4.25 µg mL-1 and ABTS: IC50 =4.82 µg mL-1 ). The peel/pulp ethanol extract (PEE) had the best anticholinesterase activity (IC50 =6.02 µg mL-1 ). Chromatographic investigation identified gallic acid, isoquercitrin, quercetin and amentoflavone in SEE, and gallic acid, isoquercitrin, quercetin and rutin in PEE. Six fatty acid methyl esters and seven triterpenes were identified, highlighting oleic acid in the seed hexane extract (61.85 %) and in the peel/pulp hexane extract (52.61 %), and betulin in the peel/pulp hexane extract (5.25 %). The substances and biological activities identified in B. sericea characterize this fruit as a functional food for future studies.

Bromelain regulates TRP channels to induce orofacial nociception relief in adult zebrafish.

Bromelain, the main protease enzyme found in the pineapple plant (Ananas comosus), has had its antinociceptive effect previously demonstrated. This investigation aimed to appraise the role of TRP (Transient Receptor Potential) channels in the nociception-relieving effects of bromelain in the orofacial region of adult zebrafish. The animals were pretreated with bromelain (3.0, 10.0 or 30.0 mg/mL; gavage) and submitted to open field and acute orofacial (capsaicin - TRPV1 agonist, cinnamaldehyde - TRPA1 agonist or menthol - TRPM8 agonist) nociception tests. The investigation also explored the contribution of central afferent C-fibers. Naive groups were included for comparison. Bromelain did not independently affect the zebrafish movement patterns. However, bromelain decreased the nociceptive responses elicited by all three TRP channel activators. Capsazepine (TRPV1 inhibitor) and AMTB (TRPM8 inhibitor), but not HC-030031 (TRPA1 inhibitor), prevented the antinociceptive effect of bromelain. Moreover, capsaicin-induced desensitization effectively nullified the antinociceptive effect of bromelain. Collectively, these findings corroborate the therapeutic relevance of bromelain as a suppressor of orofacial nociception, which seems to be intricately connected to the modulation of TRP channels.

An Update on Drug-Nutrient Interactions and Dental Decay in Older Adults.

In recent decades, the global demographic landscape has undergone a discernible shift that has been characterised by a progressive increase in the proportion of elderly individuals, indicative of an enduring global inclination toward extended lifespans. The aging process, accompanied by physiological changes and dietary patterns, contributes to detrimental deviations in micronutrient consumption. This vulnerable aging population faces heightened risks, including dental caries, due to structural and functional modifications resulting from insufficient nutritional sustenance. Factors such as physiological changes, inadequate nutrition, and the prevalence of multiple chronic pathologies leading to polypharmacy contribute to the challenge of maintaining an optimal nutritional status. This scenario increases the likelihood of drug interactions, both between medications and with nutrients and the microbiome, triggering complications such as dental decay and other pathologies. Since the drug industry is evolving and new types of food, supplements, and nutrients are being designed, there is a need for further research on the mechanisms by which drugs interfere with certain nutrients that affect homeostasis, exemplified by the prevalence of caries in the mouths of older adults. Infectious diseases, among them dental caries, exert serious impacts on the health and overall quality of life of the elderly demographic. This comprehensive review endeavours to elucidate the intricate interplay among drugs, nutrients, the microbiome, and the oral cavity environment, with the overarching objective of mitigating the potential hazards posed to both the general health and dental well-being of older adults. By scrutinising and optimising these multifaceted interactions, this examination aims to proactively minimise the susceptibility of the elderly population to a spectrum of health-related issues and the consequences associated with dental decay.

Preclinical study of experimental burns treated with photobiomodulation and Human Amniotic Membrane, both isolated and associated / Estudo pré-clínico de queimaduras experimentais tratadas com fotobiomodulação e membrana amniótica humana, isoladas e associadas / Estudio preclínico de quemaduras experimentales tratadas con fotobiomodulación y membrana amniótica humana, solas y combinadas

Abstract Objective: to evaluate the effect of photobiomodulation with low-level 660 nm laser alone or associated with Human Amniotic Membrane in the repair of partial-thickness burns in rats. Method: an experimental study conducted with 48 male Wistar rats, randomized into four groups: Control, Human Amniotic Membrane, Low-Level Laser Therapy, and Low-Level Laser Therapy associated with Human Amniotic Membrane. The histopathological characteristics of the skin samples were analyzed 7 and 14 days after the burn. The data obtained were submitted to the Kolmogorov-Smirnov and Mann-Whitney tests. Results: the histological analysis of the burn injuries showed a decrease in inflammation (p<0.0001) and an increase in proliferation of fibroblasts (p<0.0001) mainly at 7 days in all treatments related to the control group. At 14 days, the greater effectiveness in accelerating the healing process was significant (p<0.0001) in the Low-Level Laser Therapy group associated with the Human Amniotic Membrane. Conclusion: the association of photobiomodulation therapies with the Human Amniotic Membrane allowed verifying a reduction in the healing process time of the experimental lesions, stimulating its proposal as a treatment protocol in partial-thickness burns.

Resumo Objetivo: avaliar o efeito da fotobiomodulação com laser de baixa intensidade 660 nm isoladamente ou associada à membrana amniótica humana no reparo de queimaduras de espessura parcial em ratos. Método: estudo experimental com 48 ratos Wistar machos, randomizados em quatro grupos: Controle, Membrana Amniótica Humana, Terapia a Laser de Baixa Intensidade e Terapia a Laser de Baixa Intensidade associado à Membrana Amniótica Humana. As características histopatológicas das amostras de pele foram analisadas aos 7 e 14 dias após a queimadura. Os dados obtidos foram submetidos aos testes de Kolmogorov-Smirnov e Mann Whitney. Resultados: a análise histológica das lesões por queimadura mostrou a diminuição da inflamação (p <0,0001) e aumento da proliferação de fibroblastos (p <0,0001), principalmente nos 7 dias em todos os tratamentos relacionados ao grupo controle. Aos 14 dias, a maior efetividade na aceleração do processo cicatricial foi significativa (p<0,0001) no grupo Terapia a Laser de Baixa Intensidade associado à Membrana Amniótica Humana. Conclusão: a associação das terapias de fotobiomodulação à membrana amniótica humana permitiu comprovar redução no tempo do processo cicatricial das lesões experimentais, estimulando sua proposição como protocolo de tratamento em queimaduras de espessura parcial.

Resumen Objetivo: evaluar el efecto de la fotobiomodulación con láser de baja intensidad 660 nm de sola o combinada con la membrana amniótica humana en la reparación de quemaduras de espesor parcial en ratas. Método: estudio experimental con 48 ratas Wistar macho, aleatorizadas en cuatro grupos: Control, Membrana Amniótica Humana, Terapia con Láser de Baja Intensidad y Terapia con Láser de Baja Intensidad combinada con la Membrana Amniótica Humana. Las características histopatológicas de las muestras de piel fueron analizadas a los 7 y 14 días después de la quemadura. Los datos obtenidos fueron sometidos a las pruebas de Kolmogorov-Smirnov y Mann-Whitney. Resultados: el análisis histológico de las lesiones por quemadura mostró una disminución de la inflamación (p <0,0001) y un aumento de la proliferación de fibroblastos (p <0,0001) principalmente a los 7 días en todos los tratamientos en comparación con el grupo control; a los 14 días, en el grupo de Terapia con Láser de Baja Intensidad combinada con la Membrana Amniótica Humana la mayor efectividad en la aceleración del proceso de cicatrización fue significativa (p<0,0001). Conclusión: la asociación de terapias de fotobiomodulación con la membrana amniótica humana permitió comprobar que hubo una reducción en el tiempo del proceso de cicatrización de lesiones experimentales, lo cual favorece que se proponga como protocolo de tratamiento en quemaduras de espesor parcial.

Determinants of health-related quality of life and global functioning and health in axSpA, pSpA, and PsA: results from the ASAS-PerSpA study.

OBJECTIVES: We aim to identify determinants of health-related quality of life (HRQoL) and global functioning and health (GH) in axial spondyloarthritis (axSpA), peripheral spondyloarthritis (pSpA), and psoriatic arthritis (PsA). METHODS: ASAS-perSpA study data were analyzed. Models for the three patient groups were performed separately to explore factors associated with HRQoL and GH, assessed by EQ-5D and ASAS-HI, respectively. RESULTS: The analyses included 4185 patients: 2719 with axSpA, 433 with pSpA, and 1033 with PsA.In axSpA, disease activity (DA) (ß=-0.061), physical function (ß=-0.041), female sex (ß=-0.019), and fibromyalgia (ß=-0.068) were associated with worse HRQoL; age (ß = 0.001) and university education (ß = 0.014) with better HRQoL. In pSpA, DA (ß=-0.04) and physical function (ß=-0.054) were associated with worse HRQoL. In PsA, DA (ß=-0.045), physical function (ß=-0.053), axial disease (ß=-0.041), and female sex (ß=-0.028) were associated with worse HRQoL.In axSpA, DA (ß = 0.889), physical function (ß = 0.887), peripheral disease (ß = 0.564), female sex (ß = 0.812) and fibromyalgia (ß = 1.639) were associated with worse GH; age (ß=-0.013) and university education (ß=-0.274) with better GH. In pSpA, physical function (ß = 1.142), and female sex (ß = 1.060) were associated with worse GH; university education (ß=-0.611) with better GH. In PsA, DA (ß = 0.703), physical function (ß = 1.025), axial involvement (ß = 0.659), female sex (ß = 0.924), and fibromyalgia (ß = 1.387) were associated with worse GH; age (ß=-0.024) and university education (ß=-0.856) with better GH. CONCLUSIONS: DA and physical function are major HRQoL and GH determinants across spondyloarthritis types, and clinical characteristics and sociodemographic factors play an important role, highlighting the importance of a holistic approach for individual patients.

A novel perspective on the role of nucleus accumbens neurons in encoding associative learning.

The nucleus accumbens (NAc) has been considered a key brain region for encoding reward/aversion and cue-outcome associations. These processes are encoded by medium spiny neurons that express either dopamine receptor D1 (D1-MSNs) or D2 (D2-MSNs). Despite the well-established role of NAc neurons in encoding reward/aversion, the underlying processing by D1-/D2-MSNs remains largely unknown. Recent electrophysiological, optogenetic and calcium imaging studies provided insight on the complex role of D1- and D2-MSNs in these behaviours and helped to clarify their involvement in associative learning. Here, we critically discuss findings supporting an intricate and complementary role of NAc D1- and D2-MSNs in associative learning, emphasizing the need for additional studies in order to fully understand the role of these neurons in behaviour.

Assessment of eutrophication from phosphorus remobilization after resuspension of coastal sediments from an urban tropical estuary.

Dredging activities cause sediment resuspension, which can change the bioavailability of nutrients such as phosphorus (P) in aquatic ecosystems due to remobilization. This study evaluated the remobilization of P in the solid and dissolved phase before and after sediment resuspension in the Meriti and Iguaçu River estuaries and the Rio de Janeiro and Niterói harbor in Guanabara Bay (Rio de Janeiro, Brazil). Three water and sediment samples were collected at each point. Dissolved phosphorus (DP), total phosphorus (TP), organic phosphorus (OP), and inorganic phosphorus (IP) were analyzed before and after resuspension. Resuspension directly impacted the fine-grained samples, causing the release of P into the water column after resuspension, increasing eutrophication of the estuary and risk to biota. The phosphorus enrichment index (PEI) was calculated in the four areas, and in all areas, the index was above 1, which means high ecological risk. The area with sandy granulometry and a lower percentage of organic matter showed an increase in the index after resuspension. The resuspension may impact the increase of eutrophication in some areas, due to the remobilization of the sediment and the adsorbed contaminants.

Long non-coding RNA H19 regulates matrisome signature and impacts cell behavior on MSC-engineered extracellular matrices.

BACKGROUND: The vast and promising class of long non-coding RNAs (lncRNAs) has been under investigation for distinct therapeutic applications. Nevertheless, their role as molecular drivers of bone regeneration remains poorly studied. The lncRNA H19 mediates osteogenic differentiation of Mesenchymal Stem/Stromal Cells (MSCs) through the control of intracellular pathways. However, the effect of H19 on the extracellular matrix (ECM) components is still largely unknown. This research study was designed to decode the H19-mediated ECM regulatory network, and to reveal how the decellularized siH19-engineered matrices influence MSC proliferation and fate. This is particularly relevant for diseases in which the ECM regulation and remodeling processes are disrupted, such as osteoporosis. METHODS: Mass spectrometry-based quantitative proteomics analysis was used to identify ECM components, after oligonucleotides delivery to osteoporosis-derived hMSCs. Moreover, qRT-PCR, immunofluorescence and proliferation, differentiation and apoptosis assays were performed. Engineered matrices were decellularized, characterized by atomic force microscopy and repopulated with hMSC and pre-adipocytes. Clinical bone samples were characterized by histomorphometry analysis. RESULTS: Our study provides an in-depth proteome-wide and matrisome-specific analysis of the ECM proteins controlled by the lncRNA H19. Using bone marrow-isolated MSC from patients with osteoporosis, we identified fibrillin-1 (FBN1), vitronectin (VTN) and collagen triple helix repeat containing 1 (CTHRC1), among others, as having different pattern levels following H19 silencing. Decellularized siH19-engineered matrices are less dense and have a decreased collagen content compared with control matrices. Repopulation with naïve MSCs promotes a shift towards the adipogenic lineage in detriment of the osteogenic lineage and inhibits proliferation. In pre-adipocytes, these siH19-matrices enhance lipid droplets formation. Mechanistically, H19 is targeted by miR-29c, whose expression is decreased in osteoporotic bone clinical samples. Accordingly, miR-29c impacts MSC proliferation and collagen production, but does not influence ALP staining or mineralization, revealing that H19 silencing and miR-29c mimics have complementary but not overlapping functions. CONCLUSION: Our data suggest H19 as a therapeutic target to engineer the bone ECM and to control cell behavior.

Preclinical study of experimental burns treated with photobiomodulation and Human Amniotic Membrane, both isolated and associated.

OBJECTIVE: to evaluate the effect of photobiomodulation with low-level 660 nm laser alone or associated with Human Amniotic Membrane in the repair of partial-thickness burns in rats. METHOD: an experimental study conducted with 48 male Wistar rats, randomized into four groups: Control, Human Amniotic Membrane, Low-Level Laser Therapy, and Low-Level Laser Therapy associated with Human Amniotic Membrane. The histopathological characteristics of the skin samples were analyzed 7 and 14 days after the burn. The data obtained were submitted to the Kolmogorov-Smirnov and Mann-Whitney tests. RESULTS: the histological analysis of the burn injuries showed a decrease in inflammation (p<0.0001) and an increase in proliferation of fibroblasts (p<0.0001) mainly at 7 days in all treatments related to the control group. At 14 days, the greater effectiveness in accelerating the healing process was significant (p<0.0001) in the Low-Level Laser Therapy group associated with the Human Amniotic Membrane. CONCLUSION: the association of photobiomodulation therapies with the Human Amniotic Membrane allowed verifying a reduction in the healing process time of the experimental lesions, stimulating its proposal as a treatment protocol in partial-thickness burns.

Toxic profile of marinobufagin from poisonous Amazon toads and antitumoral effects on human colorectal carcinomas.

ETHNOPHARMACOLOGICAL RELEVANCE: South Americans natives have extensively used the toad "kururu" to reduce/treat skin infections, cutaneous lesions and sores. They release secretions rich in bufadienolides, polyhydroxy steroids with well-documented cardiotonic and antiproliferative actions, but in vivo antitumoral evaluations in mammals are rare, and toxicological safety has been left in second place. AIMS OF THE STUDY: This investigation used in silico, in vitro and in vivo tools to evaluate acute and subacute toxic effects of marinobufagin and the anticancer action in tumor-bearing mice models. MATERIALS AND METHODS: Initially, in silico toxic predictions were performed, followed by in vitro assays using human and murine normal and tumor lines. Next, acute and subacute studies on mice investigated the behavior, hematological and intestinal transit profile and antitumoral activity of marinobufagin in sarcoma 180- and HCT-116 colorectal carcinoma-transplanted mice for 7 and 15 days, respectively. Ex vivo and in vivo cytogenetic assays in Sarcoma 180 and bone marrow cells and histopathological examinations were also executed. RESULTS: In silico studies revealed ecotoxicological effects on crustaceans (Daphnia sp.), fishes (Pimephales promelas and Oryzias latipes), and algae. A 24-h marinobufagin-induced acute toxicity included signals of central activity, mainly (vocal frenzy, absence of body tonus, increased ventilation, ataxia, and equilibrium loss), and convulsions and death at 10 mg/kg. The bufadienolide presented effective in vitro cytotoxic action on human lines of colorectal carcinomas in a similar way to ouabain and tumor reduction in marinobufagin-treated SCID-bearing HCT-116 heterotopic xenografts. Animals under subacute nonlethal doses exhibited a decrease in creatinine clearance with normal levels of blood urea, probably as a result of a marinobufagin-induced renal perfusion fall. Nevertheless, only minor morphological side effects were identified in kidneys, livers, hearts and lungs. CONCLUSIONS: Marinobufagin has in vitro and in vivo anticancer action on colorectal carcinoma and mild and reversible alterations in key metabolic organs without direct chemotherapy-induced gastrointestinal effects at subacute exposure, but it causes acute ataxia, equilibrium loss, convulsions and death at higher acute exposure.

Mapa de evidências sobre a efetividade clínica da medicina antroposófica: informe executivo / Evidence map on the clinical effectiveness of anthroposophic medicine: executive report

O mapa apresenta uma visão geral das evidências sobre os efeitos da Medicina Antroposófica, referida na PNPIC como Antroposofia Aplicada à Saúde, em função de sua natureza multiprofissional. A partir de uma ampla busca bibliográfica foram incluídos no mapa 33 estudos de revisão que analisaram o efeito de intervenções com medicamentos antroposóficos, terapias antroposóficas e terapias multimodais para desfechos clínicos. No mapa estão representadas 63 associações entre 5 tipos de intervenções e 19 desfechos clínicos, com indicação do efeito reportado e nível de confiança da evidência reportada nos estudos. Principais Achados: • As intervenções foram organizadas em três grupos: Medicamentos Antroposóficos (Viscum album ­ 22 revisões e Outros medicamentos ­ 4 revisões), Terapias Antroposóficas (Euritmia ­ 2 revisões e Outras terapias ­ 1 revisão) e Terapias Multimodais (Em Geral ­ 4 revisões). • As intervenções foram associadas a 19 desfechos ordenados em cinco grupos: Bem-estar e Qualidade de Vida, Câncer, Atenção à Saúde, Indicadores Fisiológicos e Metabólicos e Outras Condições Patológicas. • A maioria das associações foi para o grupo de desfecho Câncer, seguido pelo grupo Bem-estar e Qualidade de Vida. Dentre os desfechos, destaque para: Qualidade de Vida (12 revisões), Sobrevida (9 revisões), Segurança do Paciente (8 revisões) e Sintomas de Quimioterapia e Radioterapia (7 revisões). • Dentre as intervenções, a maioria das associações foi para Viscum album (48 associações). • As intervenções multimodais, outros medicamentos, Euritmia e outras terapias foram associadas aos desfechos: Resultado do tratamento (5 associações), Satisfação e Segurança do paciente (2 associações cada), Infecções respiratórias (3 associações), Coordenação cardiorrespiratória, Transtornos gastrointestinais e Edema (1 associação cada). Implicações para a prática e pesquisa: • Considerando os efeitos positivos reportados (em 27 associações), destaque para o uso de medicamento antroposófico Viscum album (19 associações) para os desfechos Qualidade de Vida, Segurança do Paciente e Sintomas de Quimioterapia e Radioterapia. • Quanto aos efeitos potencialmente positivos (em 21 associações), a maioria foi associado ao Viscum album (18 associações) para os desfechos: Sobrevida ao câncer, Sintomas de Quimioterapia e Radioterapia e Qualidade de Vida. • Identificaram-se efeitos inconclusivos em 15 associações para 11 diferentes desfechos, o que sugere uma necessidade de novos estudos primários sobre intervenções com medicamentos e terapias antroposóficas. • Não foram identificados estudos com ausência de efeito ou efeitos negativos.

Evidence map on the clinical effectiveness of anthroposophic medicine: executive report

The map provides an overview of the evidence on the effects of Anthroposophic Medicine, referred to in the National Policy on Integrative and Complementary Practices (PNPIC) as applied Anthroposophy in Health, due to its multiprofessional nature. Based on an extensive literature search, the map includes 33 review studies that analyzed the effects of interventions with anthroposophic medicines, anthroposophic therapies, and multimodal therapies on clinical outcomes. The map represents 63 associations between 5 types of interventions and 19 clinical outcomes, indicating the reported effect and level of confidence in the evidence reported in the studies. Key Findings: • The interventions were organized into three groups: Anthroposophic Medicines (Viscum album - 22 reviews and Other medicines - 4 reviews), Anthroposophic Therapies (Eurythmy - 2 reviews and Other therapies - 1 review), and Multimodal Therapies (Overall - 4 reviews). • The interventions were associated with 19 outcomes grouped into five categories: Well-being and Quality of Life, Cancer, Healthcare, Physiological and Metabolic Indicators, and other Pathological Conditions. • The majority of associations were found in the Cancer outcome group, followed by the Well-being and Quality of Life group. Notable outcomes included Quality of Life (12 reviews), Survival (9 reviews), Patient Safety (8 reviews), and Chemotherapy and Radiotherapy Symptoms (7 reviews). • Among the interventions, the majority of associations were related to Viscum album (48 associations). • Multimodal interventions, other medicines, eurythmy, and other therapies were associated with outcomes such as Treatment Outcome (5 associations), Patient Satisfaction and Safety (2 associations each), Respiratory Infections (3 associations), Cardiorespiratory Coordination, Gastrointestinal Disorders, and Edema (1 association each). Implications for Practice and Research: • Considering the reported positive effects (in 27 associations), the use of anthroposophic medicines Viscum album (19 associations) stands out for Quality of Life, Patient Safety, and Chemotherapy and Radiotherapy Symptoms outcomes. • Regarding potentially positive effects (in 21 associations), the majority were associated with Viscum album (18 associations) for Cancer Survival, Chemotherapy and Radiotherapy Symptoms, and Quality of Life outcomes. • Inconclusive effects were identified in 15 associations for 11 different outcomes, suggesting a need for further primary studies on interventions with anthroposophic medicines and therapies. • No studies were identified with no effect or negative effects.

Impact of the Nutritional Status on Clinical Outcomes of Patients with Coronavirus Disease Undergoing Cancer Treatment.

Coronavirus disease (COVID-19) is a critical and potentially fatal condition. The nutritional status affects the evolution and clinical outcome throughout the disease course among factors influencing the patient prognosis. In patients with cancer, the Patient-Generated Subjective Global Assessment (PG-SGA) is the preferred instrument for assessing the nutritional status. The aim of this retrospective cross-sectional study was to evaluate the impact of the nutritional status on the clinical outcome of patients with COVID-19 undergoing cancer treatment. We enrolled 52 patients with cancer under outpatient follow-up who had been diagnosed with COVID-19 during the cancer treatment course. The PG-SGA instrument revealed age (p = 0.045) and nutritional status (p = 0.042) before infection as the main risk factors of death from COVID-19. In addition, the risk of mortality due to COVID-19 increased with the degree of malnutrition. Twelve (23.1%) of the 52 patients showed no negative effects related to COVID-19, and age below 65 years was considered to be a protective factor.

Nutritional and food education as a complementary treatment approach in severe obese individuals.

Background: The treatment for obesity, specifically severe obesity, is a challenge for health professionals and services. It requires a multidisciplinary and holistic approach covering the complexity and difficulties of incorporating healthy habits to prevent associated diseases and mortality. Individual intervention's methods are not enough to change eating habits. Objective: To describe and investigate the contribution of nutritional and food education as a complementary therapeutic approach in the treatment of individuals with severe obesity and their family members. Methods: A multidisciplinary team adopted a group approach. A different topic was addressed at each therapeutic meeting to assist in the nutritional treatment of obesity, such as diet and healthy habits i.e. barriers to lifestyle changes. The topics were developed based on different methodological and teaching approaches to facilitate adherence to non-drug treatment. Results: Overall, there was a greater understanding towards the adoption of healthy eating habits of the whole family, greater motivation to adhere to dietary changes and adoption of a more physical active lifestyle. This interventional educational support methodology had been accepted in such a positive way for patients and their relatives. Family member participation expands the possibilities of establishing necessary and lasting changes in the lifestyle of not only the patients, but their whole families. Conclusion: Health education actions constitute an important complementary therapeutic approach in promoting health and preventing complications in individuals with severe obesity. This article can be useful to enlarge the debate on the subject and face the challenges related to the effective treatment of obesity, notably severe obesity.

Ginger supplementation does not increase energy expenditure in female adults.

Food components with thermogenic properties are promising antiobesity agents. Ginger (Zingiber officinale Rosc.) bioactive compounds have a capsaicin-like vanillyl portion, which has been attributed to thermogenic effect in previous experimental studies. However, studies conducted in humans have evaluated only the acute thermogenic effect of ginger, and demonstrated contradictory results. We evaluated the effect of long-term consumption of dry ginger extract on the resting energy expenditure (REE) of female adults with high body adiposity. METHODS: This is a secondary analysis of a randomized, double-blind, placebo-controlled clinical trial (NCT02570633). Participants age 18 to 60 y were randomly assigned into two groups: Intervention (600 mg of ginger extract daily) and placebo (cellulose). The intervention lasted 3 mo. Anthropometric measurements, blood pressure, and REE were assessed at each visit. RESULTS: A total of 66 female participants with high body adiposity were included in the analysis (mean age: 29 y [range, 20-55 y]; body mass index: 23.3 ± 2.7), with 30 participants in the ginger group and 36 in the placebo group. There were no significant differences in baseline characteristics between the groups. No differences were observed for group × time interaction on REE. Body composition and blood pressure followed the same pattern (all P > 0.05). CONCLUSIONS: Ginger extract consumption for 3 mo did not change the REE, anthropometric, and clinical data of female adults with excess adiposity.

Magnetoliposomes Containing Multicore Nanoparticles and a New Antitumor Thienopyridine Compound with Potential Application in Chemo/Thermotherapy.

Multicore magnetic nanoparticles of manganese ferrite were prepared using carboxymethyl dextran as an agglutinating compound or by an innovative method using melamine as a cross-coupling agent. The nanoparticles prepared using melamine exhibited a flower-shape structure, a saturation magnetization of 6.16 emu/g and good capabilities for magnetic hyperthermia, with a specific absorption rate (SAR) of 0.14 W/g. Magnetoliposome-like structures containing the multicore nanoparticles were prepared, and their bilayer structure was confirmed by FRET (Förster Resonance Energy Transfer) assays. The nanosystems exhibited sizes in the range of 250-400 nm and a low polydispersity index. A new antitumor thienopyridine derivative, 7-[4-(pyridin-2-yl)-1H-1,2,3-triazol-1-yl]thieno[3,2-b]pyridine, active against HeLa (cervical carcinoma), MCF-7 (breast adenocarcinoma), NCI-H460 (non-small-cell lung carcinoma) and HepG2 (hepatocellular carcinoma) cell lines, was loaded in these nanocarriers, obtaining a high encapsulation efficiency of 98 ± 2.6%. The results indicate that the new magnetoliposomes can be suitable for dual cancer therapy (combined magnetic hyperthermia and chemotherapy).

Eugenol Improves Follicular Survival and Development During in vitro Culture of Goat Ovarian Tissue.

This study evaluated the effects of different concentrations (10, 20, or 40 µM) of eugenol (EUG 10, EUG 20, or EUG 40), ascorbic acid (50 µg/mL; AA) or anethole (300 µg/mL; ANE 300) on the in-vitro survival and development of goat preantral follicles and oxidative stress in the cultured ovarian tissue. Ovarian fragments from five goats were cultured for 1 or 7 days in Alpha Minimum Essential Medium (α-MEM+) supplemented or not with AA, ANE 300, EUG 10, EUG 20 or EUG 40. On day 7 of culture, when compared to MEM, the addition of EUG 40 had increased the rate of follicular development, as observed by a decrease in the proportion of primordial follicles alongside with an increase in the rate of normally developing follicles. Furthermore, EUG 40 significantly increased both follicular and oocyte diameters. Subsequently, ovarian fragments from three goats were cultured for 1 or 7 days in α-MEM+ supplemented or not with AA, ANE 300 or EUG 40. All tested antioxidants, except ANE 300, were able to significantly decrease the levels of reactive oxygen species in the ovarian tissue, but EUG 40 could most efficiently neutralize free radicals. All ovarian tissues cultured in the presence of antioxidants, especially EUG 40, presented a significant decrease in H3K4me3 labeling, indicating a silencing of genes that play a role in the inhibition of follicular activation and apoptosis induction. When compared to cultured control tissues, both EUG 40 and ANE 300 significantly increased the intensity of calreticulin labeling in growing follicles. The mRNA relative expression of ERP29 and KDM3A was significantly increased when the culture medium was supplemented with EUG 40, indicating a response to ER stress experienced during culture. In conclusion, EUG 40 improved in-vitro follicle survival, activation and development and decreased ROS production, ER stress and histone lysine methylation in goat ovarian tissue.