Silymarin Supplementation in Active Rheumatoid Arthritis: Outcomes of a Pilot Randomized Controlled Clinical Study.

Background and Objectives: Coadministration of natural products to enhance the potency of conventional antirheumatic treatment is of high interest. This study aimed to assess the impact of administration of silymarin (a nutritional supplement) in patients with active rheumatoid arthritis under treatment with conventional disease-modifying antirheumatic drugs. Materials and Methods: One-hundred and twenty-two patients diagnosed with active rheumatoid arthritis and treated with conventional disease-modifying antirheumatic drugs were randomly assigned to either control or intervention groups; the latter was supplemented with silymarin (300 mg/day) for 8 weeks. Indicators of disease activity, inflammatory markers, disease activity and disability indices, European League Against Rheumatism responses, fatigue, depression, and anxiety scores were determined at baseline and week 8. Results: Silymarin supplementation significantly reduced the number of tender and swollen joints, duration of morning stiffness, severity of pain, disease activity and disability indices, European League Against Rheumatism responses, levels of fatigue, depression, and anxiety. According to our results, silymarin substantially improved patients' general condition. Conclusions: Our study provides evidence for the benefits of silymarin supplementation to disease-modifying antirheumatic drugs in patients with active rheumatoid arthritis.

Fear of Incompetence in Family Caregivers and Dementia Care Transitions.

Research on interpersonal interaction dynamics in relationships between persons with dementia and their family caregivers has been limited. We examine the role of these dynamics in decisions to transition a family member from home care to congregate care, with a particular focus on the role of fear of incompetence. Fear of incompetence is the fear of being unable to interact, communicate in a meaningful way, or take care of a close family member with dementia. In this study (N = 350 family caregivers), perceived negative changes in the family member with dementia predicted increased perceived dependency, which predicted both increased caregiver burden and greater fear of incompetence in caregivers, which, in turn, predicted stronger care transition desire. Strategies should be aimed not only at reducing dependency of the care recipient but also teaching family caregivers interaction skills that decrease their fear of interactional incompetence and thus promote home care continuation.

Phyto-Functionalized Silver Nanoparticles Derived from Conifer Bark Extracts and Evaluation of Their Antimicrobial and Cytogenotoxic Effects.

Silver nanoparticles synthesized using plant extracts as reducing and capping agents showed various biological activities. In the present study, colloidal silver nanoparticle solutions were produced from the aqueous extracts of Picea abies and Pinus nigra bark. The phenolic profile of bark extracts was analyzed by liquid chromatography coupled to mass spectrometry. The synthesis of silver nanoparticles was monitored using UV-Vis spectroscopy by measuring the Surface Plasmon Resonance band. Silver nanoparticles were characterized by attenuated total reflection Fourier transform infrared spectroscopy, Raman spectroscopy, dynamic light scattering, scanning electron microscopy, energy dispersive X-ray and transmission electron microscopy analyses. The antimicrobial and cytogenotoxic effects of silver nanoparticles were evaluated by disk diffusion and Allium cepa assays, respectively. Picea abies and Pinus nigra bark extract derived silver nanoparticles were spherical (mean hydrodynamic diameters of 78.48 and 77.66 nm, respectively) and well dispersed, having a narrow particle size distribution (polydispersity index values of 0.334 and 0.224, respectively) and good stability (zeta potential values of -10.8 and -14.6 mV, respectively). Silver nanoparticles showed stronger antibacterial, antifungal, and antimitotic effects than the bark extracts used for their synthesis. Silver nanoparticles obtained in the present study are promising candidates for the development of novel formulations with various therapeutic applications.

Improving nursing students' perspective taking, perceptions of humanness, and attitudes toward older adults.

Whereas prior work has examined the role of nursing courses in improving empathic skills and reducing dehumanization of older adults, little research has explored how perspective taking and perceptions of humanness of older adults acquired through nursing curricula predict attitudes toward this age group. Nursing students (N = 43) completed surveys at the beginning (Time 1) and end of gerontological coursework (Time 2). Perspective taking and perceived human nature and human uniqueness of older adults increased from Time 1 to Time 2. Perceived human nature of older adults was associated with more positive attitudes at the end of the semester, compared to the beginning. Improved perceptions of the human nature of older adults also predicted lower ageism at the end of the semester. Strategies for improving perspective taking and perceptions of humanness of older adults in nursing courses are discussed.

Recent advances in tackling microbial multidrug resistance with essential oils: combinatorial and nano-based strategies.

The emergence of multidrug resistant pathogens is a great challenge to the medical field and a major global health threat requiring novel therapeutic strategies. Among plant products, essential oils have significant antimicrobial properties that make them promising agents in the fight against drug resistant human pathogens. The aim of the present review was to highlight the most important essential oil-based antimicrobial strategies as revealed by recent studies. Synergistic interactions between essential oils or their bioactive compounds in combination with known antibiotics are presented. Also, nanoformulation approaches to boost the antimicrobial activity of essential oils are reviewed in terms of bioefficiency, stability and design of the nanostructured delivery systems. The focus was mainly put on the antimicrobial activity against multi-drug resistant pathogens, also called "ESKAPE" organisms (Enterococcus spp., Staphylococcus aureus, Klebsiella spp., Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.). Thus, essential oils in combinatorial and nano-based strategies may cope with infections caused by drug-resistant bacteria and may offer possibilities for reducing antibiotic use. Research on the in vivo efficacy and safety of such strategies is required for further clinical antimicrobial chemotherapy. In this regard, the understanding of the interactions between essential oil-based strategies and biological interface is essential.

Bioactivity of dietary polyphenols: The role of metabolites.

A polyphenol-rich diet protects against chronic pathologies by modulating numerous physiological processes, such as cellular redox potential, enzymatic activity, cell proliferation and signaling transduction pathways. However, polyphenols have a low oral bioavailability mainly due to an extensive biotransformation mediated by phase I and phase II reactions in enterocytes and liver but also by gut microbiota. Despite low oral bioavailability, most polyphenols proved significant biological effects which brought into attention the low bioavailability/high bioactivity paradox. In recent years, polyphenol metabolites have attracted great interest as many of them showed similar or higher intrinsic biological effects in comparison to the parent compounds. There is a huge body of literature reporting on the biological functions of polyphenol metabolites generated by phase I and phase II metabolic reactions and gut microbiota-mediated biotransformation. In this respect, the review highlights the pharmacokinetic fate of the major dietary polyphenols (resveratrol, curcumin, quercetin, rutin, genistein, daidzein, ellagitannins, proanthocyanidins) in order to further address the efficacy of biometabolites as compared to parent molecules. The present work strongly supports the contribution of metabolites to the health benefits of polyphenols, thus offering a better perspective in understanding the role played by dietary polyphenols in human health.

6-O-(3″, 4″-di-O-trans-cinnamoyl)-α-l-rhamnopyranosylcatalpol and verbascoside: Cytotoxicity, cell cycle kinetics, apoptosis, and ROS production evaluation in tumor cells.

The aim of this study was to evaluate the impact that 6-O-(3″, 4″-di-O-trans-cinnamoyl)-α- l-rhamnopyranosylcatalpol (Dicinn) and verbascoside (Verb), two compounds simultaneously reported in Verbascum ovalifolium, have on tumor cell viability, apoptosis, cell cycle kinetics, and intracellular reactive oxygen species (ROS) level. At 100 µg/mL and 48 hours incubation time, Dicinn and Verb produced good cytotoxic effects in A549, HT-29, and MCF-7 cells. Dicinn induced cell-cycle arrest at the G0 /G1 phase and apoptosis, whereas Verb increased the population of subG1 cells and cell apoptosis rates. Furthermore, the two compounds exhibited time-dependent ROS generating effects in tumor cells (1-24 hours). Importantly, no cytotoxic effects were induced in nontumor MCF-10A cells by the two compounds up to 100 µg/mL. Overall, the effects exhibited by Verb in tumor cells were more potent, which can be correlated with its structural features, such as the presence of phenolic hydroxyl groups.

Verbascum nigrum: Cytotoxicity Evaluation in A431 Epidermoid Carcinoma Cells and Untargeted LC-HR-MS/MS Metabolite Profiling.

The crude methanolic extract obtained from Verbascum nigrum aerial parts (VNE) and its six fractions (VNF1-VNF6) were initially screened regarding their effects on the viability of immortalized HaCaT keratinocytes and A431 epidermoid carcinoma cells (MTT assay, 24 h). None of the tested samples affected the viability of HaCaT cells in a concentration range of 25-150 µg/mL. VNE and VNF4 exhibited significant cytotoxic effects in A431 cells, with IC50 values of 81.92 and 12.27 µg/mL, respectively; the selectivity index was higher than 10 for VNF4. The untargeted LC/HR-MS/MS metabolite profiling led to the tentative annotation of a total number of 23 compounds. Of these, VNE comprised mainly iridoid glycosides (harpagoside, laterioside, acylated aucubin derivatives), whereas VNF4 showed a high abundance of triterpene saponin glycosides (ilwensisaponins A and C, songarosaponins A and B), constituents known for their selective cytotoxic potential.

Prenylated phenolics as promising candidates for combination antibacterial therapy: Morusin and kuwanon G.

Combination of antibiotics with natural products is a promising strategy for potentiating antibiotic activity and overcoming antibiotic resistance. The purpose of the present study was to investigate whether morusin and kuwanon G, prenylated phenolics in Morus species, have the ability to enhance antibiotic activity and reverse antibiotic resistance in Staphylococcus aureus and Staphylococcus epidermidis. Commonly used antibiotics (oxacillin, erythromycin, gentamicin, ciprofloxacin, tetracycline, clindamycin) were selected for the combination studies. Checkerboard and time-kill assays were used to investigate potential bacteriostatic and bactericidal synergistic interactions, respectively between morusin or kuwanon G and antibiotics. According to both fractional inhibitory concentration index and response surface models, twenty combinations (14 morusin-antibiotic combinations, six kuwanon G-antibiotic combinations) displaying bacteriostatic synergy were identified, with 4-512-fold reduction in the minimum inhibitory concentration values of antibiotics in combination. Both morusin and kuwanon G reversed oxacillin resistance of methicillin-resistant Staphylococcus aureus. In addition, morusin reversed tetracycline resistance of Staphylococcus epidermidis. At half of the minimum inhibitory concentrations, combinations of morusin with oxacillin or gentamicin showed bactericidal synergy against methicillin-resistant Staphylococcus aureus. Fluorescence and differential interference contrast microscopy and scanning electron microscopy showed an increase in the membrane permeability and massive leakage of cellular content in methicillin-resistant Staphylococcus aureus exposed to morusin or kuwanon G. Overall, our findings strongly indicate that both prenylated compounds are good candidates for the development of novel antibacterial combination therapies.

HPLC-DAD-ESI-Q-TOF-MS/MS profiling of Verbascum ovalifolium Donn ex Sims and evaluation of its antioxidant and cytogenotoxic activities.

INTRODUCTION: Plant species of Verbascum genus have been intensively investigated in the last decades but most studies focused on evaluation of their biological activities; there are only few studies dealing with their chemical characterisation. OBJECTIVE: Detailed investigation of the qualitative and quantitative chemical composition, antioxidant and cytogenotoxic activities of a previously non-studied Verbascum species (V. ovalifolium Donn ex Sims). METHODS: Qualitative analysis of secondary metabolites was performed by HPLC-DAD-ESI-Q-TOF-MS/MS, whereas quantitative data were obtained through HPLC-DAD. Antioxidant activity was evaluated using in vitro assays; cytotoxic and genotoxic effects were assessed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium (MTT) and comet assays, respectively. RESULTS: More than 50 secondary bioactive metabolites belonging to various classes (iridoids, phenylethanoids, flavonoids, phenolic acids) were detected in the methanolic extract of V. ovalifolium and its fractions. The fragmentation pathways of acylated catalpol-type iridoid diglycosides are thoughtfully described herein. The extracts showed good free radical scavenging and ferric ion reducing properties correlated with phenolic, flavonoid, chlorogenic acid and verbascoside contents. Moreover, 24 h treatment of SK-MEL-2 cells with V. ovalifolium extracts produced significant changes in terms of tumour cell viability. The crude extract and the ethyl acetate fraction showed no important signs of cytogenotoxicity in non-tumour cells. CONCLUSION: The performed phytochemical and biological analyses contribute to the preclinical knowledge about V. ovalifolium and they could help exploiting it in novel herbal medicinal products.

Intracellular signaling pathways of inflammation modulated by dietary flavonoids: The most recent evidence.

Dietary flavonoids, which occur in many plant foods, are considered as the most active constituents among the plant-derived ones in vitro and in vivo. To date, many studies have addressed the anti-inflammatory activity of flavonoids. However, their considerable structural diversity and in vivo bioavailability make them able to modulate different signaling pathways. The present review attempted to summarize and highlight a broad range of inflammation-associated signaling pathways modulated by flavonoids. Finally, based on the current scientist's literature, structure-activity relationships were concluded. Dietary flavonoids have the ability to attenuate inflammation by targeting different intracellular signaling pathways triggered by NF-κB, AP-1, PPAR, Nrf2, and MAPKs. Identification of the main structural features required for the modulation of these inflammation-related pathways (hydroxylation pattern, C2=C3 double bond) have an important role to play in the development of new anti-inflammatory drugs.

Trichothecenes: immunomodulatory effects, mechanisms, and anti-cancer potential.

Paradoxically, trichothecenes have both immunosuppressive and immunostimulatory effects. The underlying mechanisms have not been fully explored. Early studies show that dose, exposure timing, and the time at which immune function is assessed influence whether trichothecenes act in an immunosuppressive or immunostimulatory fashion. Recent studies suggest that the immunomodulatory function of trichothecenes is also actively shaped by competing cell-survival and death-signaling pathways. Autophagy may also promote trichothecene immunosuppression, although the mechanism may be complicated. Moreover, trichothecenes may generate an "immune evasion" milieu that allows pathogens to escape host and vaccine immune defenses. Some trichothecenes, especially macrocyclic trichothecenes, also potently kill cancer cells. T-2 toxin conjugated with anti-cancer monoclonal antibodies significantly suppresses the growth of thymoma EL-4 cells and colon cancer cells. The type B trichothecene diacetoxyscirpenol specifically inhibits the tumor-promoting factor HIF-1 in cancer cells under hypoxic conditions. Trichothecin markedly inhibits the growth of multiple cancer cells with constitutively activated NF-κB. The type D macrocyclic toxin Verrucarin A is also a promising therapeutic candidate for leukemia, breast cancer, prostate cancer, and pancreatic cancer. The anti-cancer activities of trichothecenes have not been comprehensively summarized. Here, we first summarize the data on the immunomodulatory effects of trichothecenes and discuss recent studies that shed light on the underlying cellular and molecular mechanisms. These mechanisms include autophagy and major signaling pathways and their crosstalk. Second, the anti-cancer potential of trichothecenes and the underlying mechanisms will be discussed. We hope that this review will show how trichothecene bioactivities can be exploited to generate therapies against pathogens and cancer.

Contact and perspective taking improve humanness standards and perceptions of humanness of older adults and people with dementia: a cross-sectional survey study.

BACKGROUND: No empirical work has systematically explored perceptions of humanness of people with dementia and of older adults and the variables that could improve these perceptions. We thus investigated the role of contact and perspective taking in improving perceptions of humanness of these social groups. To do so, we developed a new concept, humanness standards, defined as the amount of evidence of ability impairment needed to conclude that elderly people and those with dementia have lost personhood. METHODS: We used a cross-sectional survey design (n = 619) to assess participants' humanness standards and perceptions of uniquely human characteristics and human nature characteristics of two social groups (people with dementia and older adults). Half the participants (n = 311) completed a survey about people with dementia and half (n = 308) assessed older adults. RESULTS: People with dementia were perceived as possessing humanness characteristics to a lesser extent than were older adults. For both groups, contact predicted enhanced perceptions of humanness characteristics. Participants' degree of contact with individuals with dementia also predicted humanness standards, but only under low perspective-taking conditions. As predicted, for older adults, participants set the highest humanness impairment thresholds in the high contact/high perspective-taking condition. CONCLUSIONS: We conclude that while social programs that bring persons with dementia and other individuals in contact could change humanness standards and perceptions of humanness characteristics of people with dementia, in the case of elderly adults, the contact must be supplemented by variables that facilitate taking the perspective of the person.

Advance on the Flavonoid C-glycosides and Health Benefits.

The dietary flavonoids, especially their glycosides, are the most vital phytochemicals in diets and are of great general interest due to their diverse bioactivity. Almost all natural flavonoids exist as their O-glycoside or C-glycoside forms in plants. The dietary flavonoid C-glycosides have received less attention than their corresponding O-glycosides. This review summarizes current knowledge regarding flavonoid C-glycosides and their influence on human health. Among the flavonoid C-glycosides, flavone C-glycosides, especially vitexin, isoorientin, orientin, isovitexin and their multiglycosides are more frequently mentioned than others. Flavonoid C-monoglycosides are poorly absorbed in human beings with very few metabolites in urine and blood and are deglycosylated and degraded by human intestinal bacteria in colon. However, flavonoid C-multiglycosides are absorbed unchanged in the intestine and distributed to other tissues. Flavonoid C-glycosides showed significant antioxidant activity, anticancer and antitumor activity, hepatoprotective activity, anti-inflammatory activity, anti-diabetes activity, antiviral activity, antibacterial and antifungal activity, and other biological effects. It looks like that the C-glycosylflavonoids in most cases showed higher antioxidant and anti-diabetes potential than their corresponding O-glycosylflavonoids and aglycones. However, there is a lack of in vivo data on the biological benefits of flavonoid C-glycosides. It is necessary to investigate more on how flavonoid C-glycosides prevent and handle the diseases.

The antioxidant, immunomodulatory, and anti-inflammatory activities of Spirulina: an overview.

Spirulina is a species of filamentous cyanobacteria that has long been used as a food supplement. In particular, Spirulina platensis and Spirulina maxima are the most important. Thanks to a high protein and vitamin content, Spirulina is used as a nutraceutical food supplement, although its other potential health benefits have attracted much attention. Oxidative stress and dysfunctional immunity cause many diseases in humans, including atherosclerosis, cardiac hypertrophy, heart failure, and hypertension. Thus, the antioxidant, immunomodulatory, and anti-inflammatory activities of these microalgae may play an important role in human health. Here, we discuss the antioxidant, immunomodulatory, and anti-inflammatory activities of Spirulina in both animals and humans, along with the underlying mechanisms. In addition, its commercial and regulatory status in different countries is discussed as well. Spirulina activates cellular antioxidant enzymes, inhibits lipid peroxidation and DNA damage, scavenges free radicals, and increases the activity of superoxide dismutase and catalase. Notably, there appears to be a threshold level above which Spirulina will taper off the antioxidant activity. Clinical trials show that Spirulina prevents skeletal muscle damage under conditions of exercise-induced oxidative stress and can stimulate the production of antibodies and up- or downregulate the expression of cytokine-encoding genes to induce immunomodulatory and anti-inflammatory responses. The molecular mechanism(s) by which Spirulina induces these activities is unclear, but phycocyanin and ß-carotene are important molecules. Moreover, Spirulina effectively regulates the ERK1/2, JNK, p38, and IκB pathways. This review provides new insight into the potential therapeutic applications of Spirulina and may provide new ideas for future studies.

Anethole and Its Role in Chronic Diseases.

Anethole is the main fragrance and bioactive compound of anise, fennel, and star anise spices and more than other 20 plant species. It is widely used as flavor agent in food industry and other industries, in cosmetics, perfumery, and pharmaceuticals. In the last few years, various studies have revealed multiple beneficial effects of anethole for human health, such as anti-inflammatory, anticarcinogenic and chemopreventive, antidiabetic, immunomodulatory, neuroprotective, or antithrombotic, that are mediated by the modulation of several cell signaling pathways, mainly NF-kB and TNF-α signaling, and various ion channels. This chapter aims to review the scientific data and attempts to provide an insight into pharmacological activity of anethole and its therapeutic potential in human chronic diseases.

Cytotoxic, Antitumor and Immunomodulatory Effects of the Water-Soluble Polysaccharides from Lotus (Nelumbo nucifera Gaertn.) Seeds.

Lotus is an edible and medicinal plant, and the extracts from its different parts exhibit various bioactivities. In the present study, the hot water-soluble polysaccharides from lotus seeds (LSPS) were evaluated for their cancer cell cytotoxicity, immunomodulatory and antitumor activities. LSPS showed significant inhibitory effects on the mouse gastric cancer MFC cells, human liver cancer HuH-7 cells and mouse hepatocarcinoma H22 cells. The animal studies showed that LSPS inhibited tumor growth in H22 tumor-bearing mice with the highest inhibition rate of 45.36%, which is comparable to that induced by cyclophosphamide (30 mg/kg) treatment (50.79%). The concentrations of white blood cells were significantly reduced in cyclophosphamide-treated groups (p < 0.01), while LSPS showed much fewer side effects according to the hematology analysis. LSPS improved the immune response in H22 tumor-bearing mice by enhancing the spleen and thymus indexes, and increasing the levels of serum cytokines including tumor necrosis factor-α and interleukin-2. Moreover, LSPS also showed in vivo antioxidant activity by increasing superoxide dismutase activity, thus reducing the malondialdehyde level in the liver tissue. These results suggested that LSPS can be used as an antitumor and immunomodulatory agent.

Flavor Chemistry of Cocoa and Cocoa Products-An Overview.

Cocoa originates from beans of the cocoa tree (Theobroma cacao L.) and it is an important commodity in the world and the main ingredient in chocolate manufacture. Its value and quality are related to unique and complex flavors. Bulk cocoas (Forastero type) exhibit strong basic cocoa notes, whereas fine varieties (Criollo, Nacional) show aromatic, floral, or smoother flavor characteristics. About 600 various compounds (alcohols, carboxylic acids, aldehydes, ketones, esters, and pyrazines) have been identified as odor-active components. The specific cocoa aroma arises from complex biochemical and chemical reactions during the postharvest processing of raw beans, and from many influences of the cocoa genotype, chemical make-up of raw seeds, environmental conditions, farming practices, processing, and manufacturing stages. There has been much research on cocoa flavor components. However, the relationships between all chemical components that are likely to play a role in cocoa flavor, their sensory properties, and the sources and mechanisms of flavor formation are not fully understood. This paper provides an overview on cocoa flavor from a compositional and a sensory perspective. The nonvolatile and volatile chemical components of cocoa and chocolate flavor, and their sensory properties correlated to the main influences involved in flavor formation, are reviewed.

Valorization of Romanian silver fir tree bark (Abies alba Mill.) wastes as low-cost sorbent of Cu(II) ions from polluted waters.

Considering recycling as the first option in the hierarchy of sustainable waste management, and also the demand for efficient processes for wastewater treatment with reduced costs, the potential applicability of Romanian Abies alba bark, the main waste from the industrial processing of the wood of mature silver fir trees, as sorbent for Cu(II) has been studied in batch conditions. It was observed that the extent of Cu(II) sorption is strongly dependent on initial solution pH, sorbent dose, initial Cu(II) ion concentration, temperature and contact time. Equilibrium data fitted very well with both Langmuir and Freundlich isotherm models. The Langmuir maximum sorption capacity of Cu(II) ions on Abies alba bark waste was found to be 7.80 mg/g at 293 K. Kinetic studies showed a high affinity of the sorption experimental data to the pseudo-second order model. Gibbs free energy was spontaneous for all interactions and the sorption process exhibited endothermic enthalpy value. The waste of Abies alba bark was successfully used for the sorption removal of Cu(II) ions from industrial electroplating wastewaters.

Vernonia kotschyana roots: therapeutic potential via antioxidant activity.

The roots of Vernonia kotschyana Sch. Bip. ex Walp. (Asteraceae) are used in Malian traditional medicine in the treatment of gastroduodenal ulcers and gastritis. Since oxidative stress is involved in gastric ulceration, the aim of this study was to screen the root extracts for their in vitro antioxidant activity and phenolic content. The roots were extracted successively with chloroform, ethyl acetate, ethanol and water. The antioxidant activity of root extracts was evaluated in both cell-free and cell-based assays. Their chemical characterization was performed by Fourier transform infrared spectroscopy (FT-IR) whereas the total phenolic content was determined by the Folin-Ciocalteu method. The ethyl acetate extract displayed the highest phenolic content and was found to be the most active in the free radical scavenging and lipid peroxidation inhibition assays; it also showed a high antioxidant activity in MCF-12F cells. This study suggests a potential use of the ethyl acetate extract of Vernonia kotschyana not only as an antioxidant agent in gastroduodenal ulcers and gastritis, but also in other disorders characterized by high levels of oxidative stress.