Clinical characteristics and therapeutic behavior of breast cancer patients using mistletoe therapy consulting a clinic offering integrative oncology: a registry data analysis.

MOTIVATION: Cancer patients often use complementary and/or alternative medicine, such as mistletoe therapy, alongside conventional cancer therapies. In Switzerland, so far not much is known about treatment patterns of breast cancer patients using integrative oncology. Solid knowledge on complementary care utilization may help to enhance integrative oncology care in Switzerland. METHODS: In this exploratory, descriptive database study, we investigated the treatment pathways of a cohort of breast cancer patients who received mistletoe therapy and were documented in the cancer registry of an anthroposophic Swiss hospital offering integrative oncology treatments. RESULTS: Patients treated with mistletoe in this cohort are in median 10 years younger than Swiss breast cancer patients as a whole. Only 5.8% of these patients were treated with mistletoe alone, while 60.5% of them supplemented chemotherapy and/or hormone therapy and/or surgery and/or radiation with mistletoe therapy. Nearly 80% of patients started conventional therapy followed by additional mistletoe therapy or started mono mistletoe therapy after completion of conventional therapies. The median time from initial diagnosis to hospital admission (inpatient and/or outpatient) was less than one year. Almost ¾ of the patients were treated in an outpatient setting only. CONCLUSION: From our data, it appears that younger breast cancer patients are more likely to use mistletoe therapy simultaneously with or following their conventional medical therapies. The extent to which these patients discuss their mistletoe therapy and eventually other complementary and/or alternative therapies with their primary oncologists is not clear from the data. We therefore recommend that (Swiss) oncologists should openly discuss the desire for integrative oncology therapies, especially with their younger breast cancer patients, in order to find the best holistic care pattern for these patients.

The Introspective Patient Experience of Mistletoe Therapy in Cancer: A Qualitative Study.

INTRODUCTION: The introspective experience of cancer patients using mistletoe therapy has received little scientific interest, although it is crucial for a holistic understanding of this therapy. This study contributes to patient-centered research and treatment by documenting the subjective experiences of individuals undergoing mistletoe therapy. METHODS: In this qualitative, explorative study, 20 outpatients with a history of various cancer types were recruited from Arlesheim Hospital (Arlesheim, Switzerland). All patients received subcutaneous mistletoe therapy for at least 2 years (median 7.5 years). Data was collected through 2 semi-structured, in-depth interviews per patient. Qualitative content analysis was applied to examine the data. The individual experience of mistletoe therapy was analyzed in relation to 6 predefined levels of human experience: physical, vital, emotional, mental, spiritual and social. In addition, 3 further aspects, considered as cross-dimensional perspectives, emerged out of the material: warmth, immune strengthening, and general wellbeing. RESULTS: Data analysis revealed considerable heterogeneity among patients' experiences with mistletoe therapy. The importance of specific aspects became apparent, such as increased vitality to manage daily life, greater emotional and mental stability, warmth as a multidimensional phenomenon, feelings of safety and protection through mistletoe therapy, heightened self-awareness and improved self-care, as well as sensations of spiritual connectedness. CONCLUSIONS: Prior to this study it had not been shown that cancer patients using mistletoe therapy do have observations on different levels of experience. These results may lead to a deeper understanding of patients receiving mistletoe therapy, enabling them to be supported in a more holistic way both during mistletoe treatment and on their life path. Further investigations into the effects of mistletoe therapy on the emotional, mental, and spiritual level are warranted.

Viscum album Induces Apoptosis by Regulating STAT3 Signaling Pathway in Breast Cancer Cells.

In this study, we investigated the potential anticancer effects of Viscum album, a parasitic plant that grows on Malus domestica (VaM) on breast cancer cells, and explored the underlying mechanisms. VaM significantly inhibited cell viability and proliferation and induced apoptosis in a dose-dependent manner. VaM also regulated cell cycle progression and effectively inhibited activation of the STAT3 signaling pathway through SHP-1. Combining VaM with low-dose doxorubicin produced a synergistic effect, highlighting its potential as a promising therapeutic. In vivo, VaM administration inhibited tumor growth and modulated key molecular markers associated with breast cancer progression. Overall, our findings provide strong evidence for the therapeutic potential of VaM in breast cancer treatment and support further studies exploring clinical applications.

Seasonal variations of triterpene acid contents in Viscum album L. on typical host trees of Hyrcanian forests.

Viscum album L. (mistletoe) is a semiparasitic plant of the Santalaceae family. A valuable group of bioactive compounds in mistletoe are triterpene acids (TTAs), which possess anti-inflammatory and anticancer properties. Parrotia persica and Carpinus betulus are the most common hosts of mistletoe in the Hyrcanian forests of Iran. This study was performed to compare the content of oleanolic acid (OA), betulinic acid (BA), and ursolic acid (UA) in the mistletoe foliage (stems and leaves) from P. persica and C. betulus in various seasons for the first time. The results showed that OA was the prevailing TTA in all samples, while UA was found in none of them. The maximum amount of OA (12.38 mg/g dry weight [DW]) and BA (1.68 mg/g DW) was detected in V. album from P. persica in summer. The minimum amount of OA (5.58 mg/g DW) and BA (0.72 mg/g DW) was observed in that growing on C. betulus in winter. However, the mistletoe from C. betulus showed the greatest level of OA in spring (9.06 mg/g DW) and BA in summer and autumn (0.92 and 0.97 mg/g DW, respectively). The data collected in this study complement existing research on this subject from around the world.

Patient' and social aspects related to complementary mistletoe therapy in patients with breast cancer: A systematic review commissioned by the German agency for Health Technology Assessment.

PURPOSE: To mitigate side effects of conventional cancer care and improve quality of life, many patients with breast cancer in German-speaking countries opt for mistletoe therapy in addition to standard treatment. To understand the value for users, we evaluated the domain "Patient and Social aspects" in a health technology assessment on complementary mistletoe therapy in patients with breast cancer. METHODS: A systematic review was conducted according to PRISMA guidelines. Fifteen electronic databases and the internet were searched. Qualitative studies were analyzed using qualitative content analysis; quantitative studies were systematically summarized in evidence tables. RESULTS: Seventeen studies out of 1203 screened publications with 4765 patients and 869 healthcare professionals were included in the review. The median proportion of patients using mistletoe therapy was 26.7% (range: 7.3-46.3%). Predictors for use were younger age and higher educational level. Main reasons for patients' use of mistletoe therapy were to leave nothing untried and to be actively involved in the treatment process. Reasons against use were related to a lack of knowledge or uncertainty regarding effectiveness and safety. Physicians mainly aimed to support the patient's physical condition as main reason for use and a lack of resources and knowledge as main reason against use. CONCLUSION: Mistletoe therapy was commonly used in the treatment of breast cancer despite a lack of scientific knowledge among patients and physicians. Transparent communication on motivation for use and its potential effect enables realistic expectations. Relatively small samples of mistletoe therapy users limit the representativeness and validity of our results.

Facile one-step synthesis of gold nanoparticles using Viscum album and evaluation of their antibacterial potential.

Nanostructure gold nanoparticles (Au NPs) are well-known biological active materials, synthesised under different environment-friendly approaches that has gained significant interest in the field of biomedicine. This study investigated a novel, fast, easy, cost-effective and the eco-friendly method to synthesise Au NPs from mediated Viscum album Linn plant extract, where the plant metabolites act as stabilising and reducing agents. The synthesised Au NPs were analysed by UV/Vis spectroscopy that gave strong signals and a sharp absorption peak at 545nm due to the presence of surface plasmon resonance (SPR) bands. In addition, energy dispersive X-ray spectroscopy (EDX) showed that strong signals of Au NPs appeared at 9.7 and 2.3keV, as the rays of light passed. X-ray diffraction recognised the crystalline material and provided information on the cell unit that the synthesised Au NPs are face-centreed cubic in structure. The diffraction of X-ray spectra showed intense peaks at 38.44°, 44.7°, 44.9° and 77.8°. The mediated V. album plant extracts and synthesised Au NPs were screened against gram-positive and gram-negative (Enterobacter , Salmonella typhi , Escheria coli and Bacillus subtilis ) bacterial strains, confirming their antibacterial potential. Au NPs showed strong antibacterial activity due to its unique steric configuration. Au NPs damaged bacterial cell membrane leading to the leakage of the cytoplasm and death of the cell.

Computational evaluation of bioactive compounds from Viscum album (mistletoe) as inhibitors of p63 for pancreatic cancer treatment.

Pancreatic ductal adenocarcinoma is an aggressive malignancy usually detectable at the advanced stage, with a 5-year survival rate of less than 8%. It has been reported that a gene called tumor-protein 63 (TP63) is expressed in an aggressive form of pancreatic cancer with a squamous signature. Thus, inhibiting the activity of p63 can be a means of treating and managing PDA. Different studies have shown that plant constituents are rich and can be a promising source for discovering drug candidates. The extract from mistletoe (Viscum album) is known to contain anticancer compounds; however, the specific molecular mechanism of the bioactive compounds is unknown. This study examines the pancreatic cancer therapeutic potential of the bioactive compounds in the flavonoid and phenolic acid constituents of mistletoe by adopting structural bioinformatics and advanced theoretical chemistry techniques via molecular docking, molecular dynamics simulation, molecular mechanics/generalized Born surface area (MM/GBSA) calculations, pharmacokinetic analysis, and density functional theory analysis. The six best compounds from the flavonoid constituent with the highest binding affinity ranging from -6.8 kcal/mol to -6.7 kcal/mol were selected with the control gemcitabine (-5.5 kcal/mol) for further computational analysis after molecular docking. Furthermore, MM/GBSA calculation showed the highest binding energy for the selected docked compounds, which validates their inhibitory potential. Hence, the molecular dynamics simulation, post-simulation analysis, pharmacokinetics model, and DFT results showed that mistletoe compounds are reliable due to their stable interaction with the target protein and drug-likeness properties.Communicated by Ramaswamy H. Sarma.

Investigations on the morpho-anatomy and histochemistry of the European mistletoe: Viscum album L. subsp. album.

Viscum album L. (Santalaceae) is an important medicinal plant traditionally used to treat several diseases, including cancer therapy. This paper provides detailed morpho-anatomical characteristics of the leaves, stems and berries of Viscum album subsp. album growing as hemi-parasite on the branches of Malus domestica (Suckow) Borkh. (Rosaceae) to aid species identification and botanical characterization. Additionally, for the first time, microchemical analyses of all tissues and Energy Dispersive X-Ray Spectroscopy analyses of the calcium oxalate crystals are provided for the first time. The plant features leathery presents green leaves with parallel veins, small yellow unisexual flowers in 3-flowered cymes, and the dioecious inflorescences usually consist of three flowers, with female flowers generating white fleshy berries, in which a seed is embedded in the mucilaginous mesocarp, normally containing two embryos. Anatomically, the analyzed leaves were isobilateral and amphistomatic, and showed straight anticlinal epidermal cell walls, thick cuticles with epicuticular wax crystalloids, and paracytic stomata. The midrib is flat on both sides and has a single vascular bundle, whereas the strongly shortened petiole is concave-convex in shape and contains five bundles. The stems show a primary structure with a ring of nine vascular bundles enclosing the pith. Calcium oxalate druses and cubic and quadrangular prisms were observed in different plant parts. The results of this study provide new microscopy information that can help in the authentication of mistletoe raw materials.

Characterization of Viscum album L. Effect on Immune Escape Proteins PD-L1, PD-L2, and MHC-I in the Prostate, Colon, Lung, and Breast Cancer Cells.

BACKGROUND: Viscum album L. (VA) preparations possess immunomodulatory properties and are used in complementary medicine to support cancer therapy. It is unclear if there is an impact of VA on the expression of immune checkpoint proteins on the surface of cancer cells. This study was designed to investigate the role of commercially available VA preparations on checkpoint programmed death ligand 1, 2 (PD-L1, PD-L2) and on major histocompatibility complex class I (MHC-I). METHODS: Four human cancer cell lines (prostate, colon, lung, and breast) were assayed for their PD-L1, PD-L2, and MHC-I level after stimulation with interferon-gamma (IFN-γ). The toxicity of mistletoe preparations for the cells was analysed. Afterwards, the effect of mistletoe preparations on the PD ligands and MHC-I was investigated. RESULTS: Surface protein analysis demonstrated that all tested tumour cell lines increased the PD-L1, PD-L2, and MHC-I-expression, but to different extents, after IFN-γ stimulation. Treatment with VA extracts did not influence the viability of the cells. The expression of PD ligands and MHC-I was not affected by incubation with the VA preparations. CONCLUSION: Our investigation concludes that VA treatment does not interfere with the expression of PD ligands or MHC-I among selected cancer cells.Viscum album L. (VA)-Präparate besitzen immunmodulatorische Eigenschaften und werden in der Komplementärmedizin zur Unterstützung in der Krebstherapie eingesetzt. Es ist jedoch unklar, ob VA einen Einfluss auf die Expression von Immuncheckpoint-Proteinen auf Krebszellen hat. In der vorliegenden Arbeit wurde ein Einfluss von handelsüblichen VA-Präparaten auf die Checkpoint-Proteine programmed death ligand 1, 2 (PD-L1, PD-L2) und major histocompatibility complex class I (MHC-I) untersucht.Vier humane Krebszelllinien der Prostata, des Dickdarms, der Lunge und Brust wurden nach Stimulation mit Interferon-gamma (IFN-γ) auf ihre PD-L1, PD-L2 und MHC-I Konzentration untersucht. Zunächst wurde die Toxizität von Mistelpräparaten auf die Tumorzellen analysiert. Anschließend erfolgte eine Charakterisierung der Wirkung von Mistelpräparaten auf die PD-Liganden und MHC-I.Die Oberflächenproteinanalysen zeigten, dass alle getesteten Tumorzelllinien nach einer IFN-γ-Stimulation die PD-L1, PD-L2 und MHC-I Expression in unterschiedlichem Ausmaß erhöhten. Die Behandlung mit verschiedenen VA-Extrakten hatte keinen Einfluss auf die Viabilität der Zellen, sowie auf die Expression der PD-Liganden und MHC-I.Unsere Untersuchung kommt zu dem Schluss, dass eine VA-Behandlung die Expression von PD-Liganden oder MHC-I in den untersuchten Krebszellen nicht beeinflusst.

Mistletoe (Viscum album L.) extract attenuates itraconazole-induced acute oxidative stress and hepatocellular injury in rats.

In the current study, the protective effect of a mistletoe extract (Helixor®, HLX) on Itraconazole (ITZ)-induced hepatocellular injury and acute oxidative stress in rats was aimed to be investigated by histological, biochemical and comet assay methods. Four groups a control group, an HLX group (5mg/kg/14days/intraperitoneally (ip)), an ITZ group (100mg/kg/14days/oral) and an HLX plus ITZ group (5mg/kg/14days/ip+100mg/kg/14days/oral) were all created from 32 female Wistar albino rats. At the end of the experiment, AST and ALT liver enzymes, total oxidant status (TOS) levels and total antioxidant status (TAS) levels, histopathological analysis and comet assay were carried out. Highest genotoxicity, higher levels of plasma AST and ALT, higher TOS, more degeneration of liver histopathology including hepatocyte degeneration, hepatocyte apoptosis and necrosis, portal/periportal inflammation, bile ductus hyperplasia and multinuclear giant cell formation were observed in ITZ group (p<0.05). As opposed to that, administration of HLX plus ITZ improved histopathological changes and DNA damage and showed a dramatic decrease in AST, ALT and TOS levels (p<0.05) and an increase in TAS level (p<0.001) when compared to ITZ group. This study showed that the antioxidant properties of HLX administration significantly decreased acute oxidative stress and hepatocellular damage in rats given ITZ.

Evaluation of quality of life in lung cancer patients receiving radiation and Viscum album L.: a real-world data study.

BACKGROUND: Lung cancer (LC) is associated with high mortality and poor quality of life (QoL). The disease as well as oncological treatments such as radiation and chemotherapy with adverse effects can impair the QoL of patients. Add-on treatment with extracts of Viscum album L. (white-berry European mistletoe, VA) has been shown to be feasible and safe and to improve the QoL of cancer patients. The aim of this study was to analyze the changes in QoL of LC patients being treated with radiation according to oncological guidelines and add-on VA treatment in a real-world setting. METHODS: A real-world data study was conducted using registry data. Self-reported QoL was assessed by the evaluation of the European Organization of Research and Treatment Health-Related Quality of Life Core Questionnaire scale (EORTC QLQ-C30). Adjusted multivariate linear regression analyses were performed to analyze factors associated with changes in QoL at 12 months. RESULTS: A total of 112 primary LC patients (all stages, 92% non-small-cell lung cancer, median age 70 (ICR: 63-75)), answered the questionnaires at first diagnosis and 12 months later. Assessment of 12 months changes in QoL revealed significant improvement of 27 points for pain (p = 0.006) and 17 points for nausea/vomiting (p = 0.005) in patients who received combined radiation and VA. In addition, significant improvements of 15 to 21 points for role (p = 0.03), physical (p = 0.02), cognitive (p = 0.04), and social functioning (p = 0.04) were observed in guideline treated patients receiving no radiation but add-on VA. CONCLUSIONS: Add-on VA therapy reveals supportive effects for the QoL of LC patients. Particularly in combination with radiation a significant reduction in pain and nausea/ vomiting has been observed. Trial registration The study received ethics approval and was retrospectively registered (DRKS00013335 on 27/11/2017).

Safety of Combined Targeted and Helixor®Viscum album L. Therapy in Breast and Gynecological Cancer Patients, a Real-World Data Study.

BACKGROUND: Newer personalized medicines including targeted therapies such as PARP inhibitors and CDK 4/6 inhibitors have been shown to improve the survival of breast and gynaecological cancer patients. However, efficacy outcomes may be ham5pered by treatment discontinuation due to targeted therapy-related adverse drug reactions or resistance. Studies have suggested that add-on mistletoe (Viscum album L., VA) improves the quality of life and ameliorates the cytotoxic side effects of standard oncological therapy in cancer patients. The primary objective of this real-world data study was to determine the safety profile of targeted therapy in combination with add-on Helixor® VA therapy compared to targeted therapy alone in breast and gynecological cancer patients. METHODS: The present study is a real-world data observational cohort study utilizing demographic and treatment data from the accredited national Network Oncology (NO) registry. The study has received ethics approval. The safety profile of targeted therapies with or without Helixor® VA therapy and safety-associated variables were evaluated by univariate and adjusted multivariable regression analyses. RESULTS: All stages of breast and gynecological cancer patients (n = 242) were on average 54.5 ± 14.2 years old. One hundred and sixty patients (66.1%) were in the control (CTRL, targeted therapy) and 82 patients (33.9%) were in the combinational (COMB, targeted plus Helixor® VA therapy) group. The addition of Helixor® VA did not hamper the safety profile (χ2 = 0.107, p-value = 0.99) of targeted therapy. Furthermore, no adverse events and a trend towards an improved targeted therapy adherence were observed in the COMB group. CONCLUSIONS: The present study is the first of its kind showing the applicability of Helixor® VA in combination with targeted therapies. The results indicate that add-on Helixor® VA does not negatively alter the safety profile of targeted therapies in breast and gynaecological cancer patients.

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.

In-Vitro Growth Kinetics of Mesenchymal Stem Cells in Cytotoxicity Tests Using Low-Diluted Viscum Album.

INTRODUCTION: The use of mesenchymal stem cells (MSC) in cytotoxicity tests is an in-vitro alternative model for predicting initial doses. Homeopathic medicines may stimulate the immune system to combat a pathology effectively and have been used for over two centuries. Viscum album (VA) extracts are widely used in the treatment of cancer, due to their immunomodulatory, cytotoxic and pro-apoptotic properties. OBJECTIVE: This study aimed to evaluate the in-vitro growth kinetics of canine MSC in relation to cytotoxicity, cell differentiation and expression of pluripotentiality markers, using a VA preparation at the D1D2 (1×10-1, 1×10-2 potency (VAD1D2). METHODS: MSC were obtained from adipose tissue sampled from a healthy dog that was undergoing an elective veterinary procedure and with its owner's permission. The experiments were performed in three groups: MSC treated with VAD1D2 or diluent or untreated (control). The cytotoxicity was evaluated by MTT assay. The differentiation was induced in three lineages, and apoptotic cell labeling was performed by an Annexin-V test. RESULTS: At the concentration of 10 µL/mL of VA, the number of cells after in-vitro culture was maintained when compared with the control (untreated) group. A significant and gradual decrease in cell viability was recorded as VA concentrations increased. The apoptosis analysis showed that VA at 20 µL/mL presented absolute percentages of initial apoptosis twice as high as at 10 µL/mL, which was similar to the control (untreated group). CONCLUSION: The results suggest that the use of efficient methods to assess the in-vitro cytotoxicity of VA-based homeopathic medicines using MSC lineages may predict the potential action at different concentrations. These findings demonstrated that VAD1D2 interferes with canine MSC growth kinetics.

The essential oil compositions of three Sicilian accessions of Viscum album L. growing on three different host trees.

Viscum album L., (Common Mistletoe), is a hemiparasitic shrub that lives on a wide range of woody plant species, known since Neolithic period for its ritual and for pharmacological properties. Up to now, no investigation has been reported on the chemical composition of the essential oils of V. album aerial parts in relation with the diverse host trees. Consequently, the essential oils compositions of three Sicilian accession of V. album, growing on Quercus suber L., Crataegus monogyna Jacq. and Olea europaea L. var. europaea cv. 'Santagatese', respectively, were evaluated by GC-MS. The three populations showed quite different profiles indicating that the nature of the host considerably influences the chemical composition of the guest plant, V. album.

The future of Viscum album L. in Europe will be shaped by temperature and host availability.

Viscum album L. is a plant of great importance due to its influence on the host trees and, by extension, entire ecosystems. The species is also significant to humans-on the one hand, because of its use in medicine, and on the other, because of the growing threat it poses to the stability of conifer stands. Therefore, it is important to recognize the future range of three mistletoe subspecies (Viscum album subsp. album, V. album subsp. austriacum, and V. album subsp. abietis). Modelling of the potential range of these subspecies was performed using MAXENT software. Locations were collected from literature and databases. A total number of 3335 stands were used. Bioclimatic data for the current conditions and three future scenarios (SSP 1.26, SSP 3.70, SSP 5.85) were downloaded from the CHELSA database. The results confirmed that the temperature is the key variable on the potential range of the analysed subspecies. V. album subsp. abietis is withdrawing from its range according to all scenarios. In the case of V. album subsp. austriacum, a slight range shift is visible. Only the V. album subsp. album will expand non-directionally. The reason is most likely a very large number of host species and greater genetic variability compared to the subspecies found on conifers.

Selective Immune Modulating Activities of Viscum album and Its Components; A Possibility of Therapeutics on Skin Rash Induced by EGFR Inhibitors.

Viscum album var. coloratum (Kom.) Ohwi is a traditional herbal medicine used in East Asia to treat hypertension, skeletal muscle disorders, and cancer. The inhibitory effects of Viscum album (VA) extract on chemokines and its therapeutic potential in erlotinib-induced skin rash were investigated in this study. ELISA was used to measure the levels of chemokines, MCP-1 and RANTES, which are thought to be mediators of erlotinib-induced skin rash in RAW264.7 cells. Western blot analysis was used to look into the activation of signaling pathways like AKT, MAPK, and EGF. In order to investigate the active compounds in VA extract, solvent fractionation and preparative HPLC were performed sequentially. VA extract significantly reduced the production of TNF-α, MCP-1, and RANTES but not IL-1. Furthermore, macrophage transmigration was inhibited without causing cell toxicity. VA extract had no effect on the phosphorylation of EGF receptors stimulated by EGF or suppressed by erlotinib in both A549, a non-small cell lung cancer cells, and Hacat, a human skin keratinocyte. The isolated viscumneoside III and viscumneoside V from VA extract significantly suppressed the expression of MCP-1, according to activity guided fractionation with organic solvent fractionation and preparative HPLC. These findings suggest that VA extract and its active compounds, viscumneoside III and viscumneoside V, regulate MCP-1 production and may have the potential to suppress erlotinib-induced skin toxicity by modulating macrophage activity without neutralizing anti-cancer efficacy.

Deep learning applied to analyze patterns from evaporated droplets of Viscum album extracts.

This paper introduces a deep learning based methodology for analyzing the self-assembled, fractal-like structures formed in evaporated droplets. To this end, an extensive image database of such structures of the plant extract Viscum album Quercus [Formula: see text] was used, prepared by three different mixing procedures (turbulent, laminar, and diffusion based). The proposed pattern analysis approach is based on two stages: (1) automatic selection of patches that exhibit rich texture along the database; and (2) clustering of patches in accordance with prevalent texture by means of a Dense Convolutional Neural Network. The fractality of the patterns in each cluster is verified through Local Connected Fractal Dimension histograms. Experiments with Gray-Level Co-Occurrence matrices are performed to determine the benefit of the proposed approach in comparison with well established image analysis techniques. For the investigated plant extract, significant differences were found between the production modalities; whereas the patterns obtained by laminar flow showed the highest fractal structure, the patterns obtained by the application of turbulent mixture exhibited the lowest fractality. Our approach is the first to analyze, at the pure image level, the clustering properties of regions of interest within a database of evaporated droplets. This allows a greater description and differentiation of the patterns formed through different mixing procedures.

Additional treatment with mistletoe extracts for patients with breast cancer compared to conventional cancer therapy alone - efficacy and safety, costs and cost-effectiveness, patients and social aspects, and ethical assessment.

Background: Chemotherapy is often used in the treatment of breast cancer in women. Side effects such as diarrhea, fatigue, hair loss, fever or disturbances in blood formation impair the women's quality of life. An essential treatment goal of the accompanying mistletoe therapy (MT) used in complementary medicine is to improve the health-related quality of life during cancer therapy. Aim and methods: The HTA report on which this article is based examines the medical efficacy and safety, costs and cost-effectiveness, patient and social aspects, and ethical aspects of MT in women with breast cancer. Systematic reviews were conducted for this purpose. The search period of the literature search ranged from 2004 to October 2020. Results: A total of 2 evidence-based medical guidelines, 3 randomized trials assessing efficacy and 1 additional non-randomized intervention trial, as well as 3 observational studies assessing safety, a cost analysis, 12 cross-sectional studies on patient aspects and 17 articles on ethical evaluation were included. Improvements in health-related quality of life compared to the control group were small to moderate. Due to the high risk of bias in the studies, it is possible that the difference is not caused by MT. One study with a small sample size showed no effect on progression-free survival after 5 years. Studies on the effect of MT on overall survival are lacking. In seven studies, local skin reactions of low and moderate severity were reported in a median of 25% (range 5 to 94%) of patients, and mild to moderate systemic reactions in a median of 2% (range 0 to 8%) of patients. A comparative cost analysis from Germany reported significantly lower medical costs within 5 years after surgery for patients with MT than for patients without MT, but the underlying observational study did not control for systematic bias. With regard to patient aspects, the frequency of use and the reasons for use from the patient's or practitioner's point of view were mainly investigated. A median of 25% (range 7 to 46%) of patients with breast cancer and 29% (range 29 to 79%) of treatment providers use MT. The main motivations of patients for use were to reduce side effects, strengthen the immune system and take an active role in the treatment process. Patients felt insufficiently advised. Studies on other aspects are lacking. The ethical evaluation was able to identify 6 overarching themes; the central challenge is the insufficient evidence on efficacy and safety.