Chemical Properties and Biological Activity of Bee Pollen.

Pollen, a remarkably versatile natural compound collected by bees for its abundant source of proteins and nutrients, represents a rich reservoir of diverse bioactive compounds with noteworthy chemical and therapeutic potential. Its extensive biological effects have been known and exploited since ancient times. Today, there is an increased interest in finding natural compounds against oxidative stress, a factor that contributes to various diseases. Recent research has unraveled a multitude of biological activities associated with bee pollen, ranging from antioxidant, anti-inflammatory, antimicrobial, and antifungal properties to potential antiviral and anticancer applications. Comprehending the extensive repertoire of biological properties across various pollen sources remains challenging. By investigating a spectrum of pollen types and their chemical composition, this review produces an updated analysis of the bioactive constituents and the therapeutic prospects they offer. This review emphasizes the necessity for further exploration and standardization of diverse pollen sources and bioactive compounds that could contribute to the development of innovative therapies.

Diaza-1,3-butadienes as Useful Intermediate in Heterocycles Synthesis.

Many heterocyclic compounds can be synthetized using diaza-1,3-butadienes (DADs) as key structural precursors. Isolated and in situ diaza-1,3-butadienes, produced from their respective precursors (typically imines and hydrazones) under a variety of conditions, can both react with a wide range of substrates in many kinds of reactions. Most of these reactions discussed here include nucleophilic additions, Michael-type reactions, cycloadditions, Diels-Alder, inverse electron demand Diels-Alder, and aza-Diels-Alder reactions. This review focuses on the reports during the last 10 years employing 1,2-diaza-, 1,3-diaza-, 2,3-diaza-, and 1,4-diaza-1,3-butadienes as intermediates to synthesize heterocycles such as indole, pyrazole, 1,2,3-triazole, imidazoline, pyrimidinone, pyrazoline, -lactam, and imidazolidine, among others. Fused heterocycles, such as quinazoline, isoquinoline, and dihydroquinoxaline derivatives, are also included in the review.

Evaluation of Biological Activity of Natural Compounds: Current Trends and Methods.

Natural compounds have diverse structures and are present in different forms of life. Metabolites such as tannins, anthocyanins, and alkaloids, among others, serve as a defense mechanism in live organisms and are undoubtedly compounds of interest for the food, cosmetic, and pharmaceutical industries. Plants, bacteria, and insects represent sources of biomolecules with diverse activities, which are in many cases poorly studied. To use these molecules for different applications, it is essential to know their structure, concentrations, and biological activity potential. In vitro techniques that evaluate the biological activity of the molecules of interest have been developed since the 1950s. Currently, different methodologies have emerged to overcome some of the limitations of these traditional techniques, mainly via reductions in time and costs. These emerging technologies continue to appear due to the urgent need to expand the analysis capacity of a growing number of reported biomolecules. This review presents an updated summary of the conventional and relevant methods to evaluate the natural compounds' biological activity in vitro.

Synthesis, Experimental and Theoretical Study of Azidochromones.

A series of 2-(haloalkyl)-3-azidomethyl and 6-azido chromones has been synthetized, characterized and studied by theoretical (DFT calculations) and spectroscopic methods (UV-Vis, NMR). The crystal structure of 3-azidomethyl-2-difluoromethyl chromone, determined by X-ray diffraction methods, shows a planar framework due to extended π-bond delocalization. Its molecular packing is stabilized by F···H, N···H and O···H hydrogen bonds, π···π stacking and C-O···π intermolecular interactions. Moreover, AIM, NCI and Hirshfeld analysis evidenced that azido moiety has a significant role in the stabilization of crystal packing through weak intermolecular interactions, where analysis of electronic density suggested closed-shell (CS) interatomic interactions.

Synthesis and Evaluation of Biological Activities of Bis(spiropyrazolone)cyclopropanes: A Potential Application against Leishmaniasis.

This work focuses on the search and development of drugs that may become new alternatives to the commercial drugs currently available for treatment of leishmaniasis. We have designed and synthesized 12 derivatives of bis(spiropyrazolone)cyclopropanes. We then characterized their potential application in therapeutic use. For this, the in vitro biological activities against three eukaryotic models-S. cerevisiae, five cancer cell lines, and the parasite L. mexicana-were evaluated. In addition, cytotoxicity against non-cancerous mammalian cells has been evaluated and other properties of interest have been characterized, such as genotoxicity, antioxidant properties and, in silico predictive adsorption, distribution, metabolism, and excretion (ADME). The results that we present here represent a first screening, indicating two derivatives of bis(spiropyrazolone)cyclopropanes as good candidates for the treatment of leishmaniasis. They have good specificity against parasites with respect to mammalian cells.

Characterization of Antimicrobial, Antioxidant, and Leishmanicidal Activities of Schiff Base Derivatives of 4-Aminoantipyrine.

Our main interest is the characterization of compounds to support the development of alternatives to currently marketed drugs that are losing effectiveness due to the development of resistance. Schiff bases are promising biologically interesting compounds having a wide range of pharmaceutical properties, including anti-inflammatory, antipyretic, and antimicrobial activities, among others. In this work, we have synthesized 12 Schiff base derivatives of 4-aminoantipyrine. In vitro antimicrobial, antioxidant, and cytotoxicity properties are analyzed, as well as in silico predictive adsorption, distribution, metabolism, and excretion (ADME) and bioactivity scores. Results identify two potential Schiff bases: one effective against E. faecalis and the other with antioxidant activity. Both have reasonable ADME scores and provides a scaffold for developing more effective compounds in the future. Initial studies are usually limited to laboratory in vitro approaches, and following these initial studies, much research is needed before a drug can reach the clinic. Nevertheless, these laboratory approaches are mandatory and constitute a first filter to discriminate among potential drug candidates and chemical compounds that should be discarded.

[Inflammatory myofibroblastic tumor: Variable presentation of the same pathology]. / Tumor miofibroblástico inflamatorio: Presentación variable de una misma patología.

INTRODUCTION: The inflammatory myofibroblastic tumor is an infrequent benign neoplasm with unpredictable cli nical behavior. OBJECTIVES: to describe three clinical cases at the San Borja Arriarán Clinical Hospital between March 2014 and January 2018 and to carry out an updated review of the literature. Case 1: 14-year-old male adolescent, hospitalized due to abdominal pain, diagnosed with jejunojejunal intus susception secondary to an intestinal wall tumor. The histology was compatible with an inflamma tory myofibroblastic tumor. Case 2: 12-year-old female adolescent, hospitalized due to pneumonia and low-back pain under study associated with weight loss. A retroperitoneal mass was diagnosed involving the right psoas muscle, paravertebral muscles, vertebrae, right kidney, and ipsilateral dia phragm. A puncture biopsy was performed and the result was compatible with an inflammatory myofibroblastic tumor. Case 3: 11-year-old female pre-adolescent, hospitalized to study recurrent urinary tract infection. A bladder tumor was identified, and the biopsy showed compatibility with inflammatory myofibroblastic tumor. CONCLUSION: Due to the variable behavior of the inflammatory myofibroblastic tumor, its management will depend on the location, expression of the anaplastic lymphoma kinase (ALK), tumor behavior, and the resection possibility.

A longitudinal examination of different etiological pathways to alcohol use and misuse.

BACKGROUND: Sher, Grekin, and Williams (2005) pointed out the existence of 4 main etiological, but not mutually exclusive, models that might explain the development of alcohol use and misuse. The aim of the present study was to explore 3 of these 4 pathways in which psychological (personality and drinking motives) and environmental (child maltreatment) variables may play a relevant role: positive affect regulation, negative affect regulation, and deviance proneness. METHODS: Three hundred and fourteen young adults in the 18 to 29 year age range completed different personality, alcohol use, and child maltreatment questionnaires at Time 1. Five years later, they responded to drinking motives, antisocial behavior, alcohol use, and alcohol-related problems questionnaires. RESULTS: The path analyses showed that emotional abuse predicted negative emotionality, which, in turn, prospectively predicted alcohol-related problems through coping-with-depression drinking motives (negative affect regulation). Emotional neglect predicted lesser positive emotionality, and physical abuse predicted unconscientious disinhibition personality characteristics. In turn, these 2 broad personality domains predicted drinking at weekends at Time 2 through enhancement drinking motives (positive affect regulation). Finally, physical neglect predicted disagreeable disinhibition, and both disinhibition domains directly predicted antisocial behavior 5 years later which, in turn, predicted drinking at weekends, drinking on weekdays, and alcohol-related problems (deviance proneness). CONCLUSIONS: The findings describe the specific role of distal (maltreatment and personality) and more proximal (antisocial behavior and drinking motives) variables in the different pathways involved in the development of alcohol use and misuse.

Bioactive Compound Profiling and Antioxidant Activity of Phytelephas tenuicaulis and Other Amazonian Fruits.

The Amazon region is home to many plant species, many of which have not been studied. The objective was to evaluate the physicochemical properties, bioactive compounds, and antioxidant activity of Phytelephas tenuicalis (tintiuk), Grias neuberthii (apai), Euterpe oleracea (acai), and Mauritia flexuosa (brown moriche). Physicochemical analyses were carried out on fresh fruit from local markets. Bioactive compounds (carotenoids, phenolics, vitamin C, and organic acids) were quantified in the freeze-dried pulp by rapid-resolution liquid chromatography (RRLC), and antioxidant activity was determined by ABTS and DPPH assays. The results showed high soluble solids (10.7 °Brix) and ascorbic acid (67.3 mg/100 g DW) in tintiuk; ß-carotene (63.4 mg/100 g DW) and malic acid (19.6 g/100 g DW) in brown moriche; quercetin (944.2 mg/100 g DW) and antioxidant activity by ABTS (6.7 mmol ET/100 g DW) in apai; and citric acid (2.1 g/100 g DW) in acai. These results indicate interesting bioactive properties that could increase the consumption of these fruits nationally and internationally, benefiting local farmers and stimulating the development of new products in functional food, medicine, and cosmetics.

Functional and Antioxidant Evaluation of Two Ecotypes of Control and Grafted Tree Tomato (Solanum betaceum) at Different Altitudes.

Tree tomato (Solanum betaceum) is susceptible to nematode attack; for this reason, grafting is used as an alternative to reduce this impact. In this study, the bioactive compounds of the fruit (shell, pulp, and seed jelly) of two tree tomato ecotypes ('giant orange' and 'giant purple') were evaluated in both control and grafted plants grown at different altitudes (2010-2250, 2260-2500, 2510-2750 and 2760-3000 masl). Commercial quality, vitamin C, organic acids, phenolics, carotenoids and antioxidant activity were determined by microextraction and quantified by liquid chromatography (RRLC) or spectrophotometry (microplate reader). The results showed high concentrations of vitamin C, organic acids and antioxidant activity in the seed jelly, organic acids in the pulp and phenolic compounds, carotenoids, and antioxidant activity in the shell. The main phenolics were ferulic acid, caffeic acid and luteolin, while the main carotenoids were lutein, B-cryptoxanthin and B-carotene. Multivariate analysis showed that tree tomato quality was mainly influenced by altitude and fruit part and that grafting positively affected soluble solids for both ecotypes and all altitudes.

Iron Oxide Nanoparticles: Green Synthesis and Their Antimicrobial Activity.

The rise of antimicrobial resistance caused by inappropriate use of these agents in various settings has become a global health threat. Nanotechnology offers the potential for the synthesis of nanoparticles (NPs) with antimicrobial activity, such as iron oxide nanoparticles (IONPs). The use of IONPs is a promising way to overcome antimicrobial resistance or pathogenicity because of their ability to interact with several biological molecules and to inhibit microbial growth. In this review, we outline the pivotal findings over the past decade concerning methods for the green synthesis of IONPs using bacteria, fungi, plants, and organic waste. Subsequently, we delve into the primary challenges encountered in green synthesis utilizing diverse organisms and organic materials. Furthermore, we compile the most common methods employed for the characterization of these IONPs. To conclude, we highlight the applications of these IONPs as promising antibacterial, antifungal, antiparasitic, and antiviral agents.

Evaluation of Bioactive Compounds and Antioxidant Activity in 51 Minor Tropical Fruits of Ecuador.

Less common tropical fruits have been the subject of little research, leaving a vast field to be explored. In this context, a comprehensive study was carried out on the bioactive compounds and antioxidant capacity of 51 non-traditional fruits consumed in Ecuador. Vitamin C, organic acids, carotenoids, and phenolic compounds were evaluated using microextraction and rapid resolution liquid chromatography (RRLC) techniques, while antioxidant activity was measured using microplate readings. The results showed high levels of vitamin C (768.2 mg/100 g DW) in Dovyalis hebecarpa, total organic acids (37.2 g/100 g DW) in Passiflora tripartita, carotenoids (487.0 mg/100 g DW) in Momordica charantia, phenolic compounds (535.4 mg/g DW) in Nephelium lappaceum, Pourouma cecropiifolia (161.4 µmol TE/g DW) and Morus alba (80.5 µmol AAE/g DW) in antioxidant activity. Effective extraction of carotenoids was also observed using a mixture of methanol: acetone: dichloromethane (1:1:2) with an extraction time of 2 min, while an 80% solution of 0.1% acidified methanol with hydrochloric acid with an extraction time of 3 min was highly effective for phenolics in fruit. These results provide a valuable basis for optimising future extraction processes of bioactive compounds from non-traditional fruits, with significant implications for their potential use in various nutritional and pharmaceutical contexts.

Nude and Modified Electrospun Nanofibers, Application to Air Purification.

Air transports several pollutants, including particulate matter (PM), which can produce cardiovascular and respiratory diseases. Thus, it is a challenge to control pollutant emissions before releasing them to the environment. Until now, filtration has been the most efficient processes for removing PM. Therefore, the electrospinning procedure has been applied to obtain membranes with a high filtration efficiency and low pressure drop. This review addressed the synthesis of polymers that are used for fabricating high-performance membranes by electrospinning to remove air pollutants. Then, the most influential parameters to produce electrospun membranes are indicated. The main results show that electrospun membranes are an excellent alternative to having air filters due to the versatility of the process, the capacity for controlling the fiber diameter, porosity, high filtration efficiency and low-pressure drop.

Crystal Structure, Hirshfeld Surface Analysis, and Biological Activities of Schiff-Base Derivatives of 4-Aminoantipyrine.

Eight Schiff bases, synthesized by the reaction of 4-aminoantipyrine with different cinnamaldehydes, were studied in the solid state by using vibrational spectroscopy (IR) and X-ray diffraction techniques. The analysis was extended to the solution phase through ultraviolet-vis, fluorescence spectroscopy, and cyclic voltammetry. Finally, the crystal structures of four compounds (3b, 3d, 3g, and 3h) were determined and studied. In addition to the experimental study, theoretical calculations using the semiempirical method PM6/ZDO were performed to understand better the compound's molecular properties, UV-vis, and infrared spectra. The primary difference is the angular conformation of the terminal phenyl rings around the corresponding linking C-N and C-C σ-bonds. Furthermore, as a result of extended bonding, the > C=N- azomethine group-containing Cpyr-N=(CH)-(CR)=(CH)-Cbz chain (with R=H for 3b, 3d, and 3h, and R=CH3 for 3g) is planar, nearly coplanar, with the mean plane of the pyrazole ring. Hirshfeld surface (HS) analysis was used to investigate the crystal packing and intermolecular interactions, which revealed that intermolecular C-H···O and C-H···N hydrogen bonds, π···π stacking, and C-H···π and C=O···π interactions stabilize the compounds. The energy contributions to the lattice energies of potential hydrogen bonds were primarily dispersive and repulsive. All derivatives were tested in vitro on LPS-stimulated mouse macrophages to assess their ability to suppress the LPS-induced inflammatory responses. Only a slight reduction in the level of NO production was found in activated macrophages treated with 3h. Additionally, the derivatives were tested for antimicrobial activity against several clinical bacteria and fungi strains, including three biofilm-forming microorganisms. Nevertheless, only Schiff base 3f showed interesting antibacterial activities with minimum inhibitory concentration (MIC) values as low as 15.6 µM against Enterobacter gergoviae. On the other hand, Schiff base 3f and, to a lesser extent, 3b and 3h showed antifungal activity against clinical isolates of Candida. The lowest MIC value was for 3f against Candida albicans (15.6 µM). It is interesting to note that the same Schiff bases exhibit the highest activity in both biological evaluations.

Oxidative inactivation of the lipid phosphatase phosphatase and tensin homolog on chromosome ten (PTEN) as a novel mechanism of acquired long QT syndrome.

The most common cause of cardiac side effects of pharmaco-therapy is acquired long QT syndrome, which is characterized by abnormal cardiac repolarization and most often caused by direct blockade of the cardiac potassium channel human ether a-go-go-related gene (hERG). However, little is known about therapeutic compounds that target ion channels other than hERG. We have discovered that arsenic trioxide (As(2)O(3)), a very potent antineoplastic compound for the treatment of acute promyelocytic leukemia, is proarrhythmic via two separate mechanisms: a well characterized inhibition of hERG/I(Kr) trafficking and a poorly understood increase of cardiac calcium currents. We have analyzed the latter mechanism in the present study using biochemical and electrophysiological methods. We find that oxidative inactivation of the lipid phosphatase PTEN by As(2)O(3) enhances cardiac calcium currents in the therapeutic concentration range via a PI3Kα-dependent increase in phosphatidylinositol 3,4,5-triphosphate (PIP(3)) production. In guinea pig ventricular myocytes, even a modest reduction in PTEN activity is sufficient to increase cellular PIP(3) levels. Under control conditions, PIP(3) levels are kept low by PTEN and do not affect calcium current amplitudes. Based on pharmacological experiments and intracellular infusion of PIP(3), we propose that in guinea pig ventricular myocytes, PIP(3) regulates calcium currents independently of the protein kinase Akt along a pathway that includes a secondary oxidation-sensitive target. Overall, our report describes a novel form of acquired long QT syndrome where the target modified by As(2)O(3) is an intracellular signaling cascade.

An Approach to the Unified Conceptualization, Definition, and Characterization of Social Resilience.

The purpose of this article is to offer a synthesis of the characteristics of social resilience, integrating the different approaches received from the social sciences. We propose to focus this conceptual framework as a previous and necessary step for the later study of the possible ways of promotion of this social resilience, that will help to strengthen the welfare and public health systems. The paper explores the difficulties in defining these characteristics, identifying their constituent elements. After this, the paper study the challenges to the future development of resilience models, showing the ways that offer some advances. Finally, we conclude that the social resilience must be conceived as a dynamic, multi-level, and evolutionary process if we are to help societies not only cope with adversity but also to adapt and transform themselves.

Evaluation of the Anti-Leishmania mexicana and -Trypanosoma brucei Activity and Mode of Action of 4,4'-(Arylmethylene)bis(3-methyl-1-phenyl-1H-pyrazol-5-ol).

Trypanosomiasis and leishmaniasis are neglected infections caused by trypanosomatid parasites. The first-line treatments have many adverse effects, high costs, and are prone to resistance development, hence the necessity for new chemotherapeutic options. In line with this, twenty five 4,4'-(arylmethylene)bis(1H-pyrazol-5-ols) derivatives were synthesized and evaluated in vitro for their anti-trypanosomatid activity. Ten and five compounds from this series showed IC50 ≤ 10 µM against the promastigote and the bloodstream stage of Leishmania mexicana and Trypanosoma brucei brucei, respectively. Overall, derivatives with pyrazole rings substituted with electron-withdrawing groups proved more active than those with electron-donating groups. The hits proved moderately selective towards L. mexicana and T. brucei (selectivity index, SI, compared to murine macrophages = 5−26). The exception was one derivative displaying an SI (>111−189) against T. brucei that surpassed, by >6-fold, the selectivity of the clinical drug nifurtimox (SI = 13−28.5). Despite sharing a common scaffold, the hits differed in their mechanism of action, with halogenated derivatives inducing a rapid and marked intracellular oxidative milieu in infective T. brucei. Notably, most of the hits presented better absorption, distribution, metabolism, and excretion (ADME) properties than the reference drugs. Several of the bioactive molecules herein identified represent a promising starting point for further improvement of their trypanosomatid potency and selectivity.

Childhood abuse, the BDNF-Val66Met polymorphism and adult psychotic-like experiences.

BACKGROUND: The well-established relationship between childhood adversity and psychosis is likely to involve other factors such as genetic variants that can help us to understand why not everyone exposed to adverse events develops psychotic symptoms later in life. AIMS: We investigated the influence of childhood abuse and neglect on positive and negative psychotic-like experiences in adulthood and the potential moderating effect of the BDNF-Val66Met polymorphism. METHOD: Psychotic-like experiences and childhood adversity were assessed in 533 individuals from the general population. RESULTS: Childhood abuse showed a strong independent effect on the positive dimension of psychotic-like experiences (ß = 0.16, s.e. = 0.05, P = 0.002). Furthermore, this association was moderated by the BDNF-Val66Met polymorphism (ß = 0.27, s.e. = 0.10, P = 0.004). CONCLUSIONS: Individuals exposed to childhood abuse are more likely to report positive psychotic-like experiences. Met carriers reported more positive psychotic-like experiences when exposed to childhood abuse than did individuals carrying the Val/Val genotype. Therefore, the observed gene-environment interaction effect may be partially responsible for individual variation in response to childhood abuse.

Drinking motives in clinical and general populations.

AIMS: This paper had three aims: (1) to validate a Spanish adaptation of the Modified Drinking Motives Questionnaire-Revised (M DMQ-R), (2) to explore the relationship of each drinking motive with different patterns of alcohol use, and (3) to compare the drinking motives of moderate drinkers, heavy drinkers, and alcohol abusing/dependent individuals. METHODS: Two studies were carried out. In Study 1, a sample of 488 participants completed the M DMQ-R and a self-report scale of alcohol consumption in order to study the factor structure and different indices of reliability and validity of the Spanish M DMQ-R. In Study 2, we compared the drinking motives of moderate and heavy drinkers from Study 1 and an additional sample of 59 clinical drinkers. RESULTS: The M DMQ-R demonstrated sound reliability and validity indices. Coping-with-anxiety, social, and enhancement motives predicted higher alcohol use on weekends, but only coping-with-anxiety and social motives were related to consumption on weekdays. Furthermore, moderate drinkers had the lowest scores for all motives, whereas alcohol-dependent participants obtained the highest scores for negative reinforcement drinking motives. CONCLUSION: The Spanish M DMQ-R is a reliable and valid measure of drinking motives and has potential for assisting with treatment planning for problem drinkers.

Synthesis of 4,4'-(arylmethylene)bis(3-methyl-1-phenyl-1H-pyrazol-5-ols) and evaluation of their antioxidant and anticancer activities.

BACKGROUND: Pyrazoles have attracted particular attention due to the diverse biological activities associated with this heterocyclic system, and some have been shown to be cytotoxic to several human cell lines. Several drugs currently on the market have this heterocycle as the key structural motif, and some have been approved for the treatment of different types of cancer. RESULTS: 4,4'-(Arylmethylene)bis(1H-pyrazol-5-ols) derivatives 3a-q were synthetized by a three components reaction of 3-methyl-1-phenyl-5-pyrazolone (1) with various benzaldehydes 2 catalyzed by sodium acetate at room temperature. The structures of all synthesized compounds were characterized by physicochemical properties and spectral means (IR and NMR) and were evaluated for their radical scavenging activity by DPPH assay and tested in vitro on colorectal RKO carcinoma cells in order to determine their cytotoxic properties. All 4,4'-(arylmethylene)bis(1H-pyrazol-5-ols) derivatives 3a-q were synthetized in high to excellent yield, and pure products were isolated by simple filtration. All compounds have good radical scavenging activity, and half of them are more active than ascorbic acid used as standard. CONCLUSION: Several derivatives proved to be cytotoxic in the RKO cell line. In particular, compound 3i proved to be a very potent scavenger with an IC50 of 6.2 ± 0.6 µM and exhibited an IC50 of 9.9 ± 1.1 µM against RKO cell. Autophagy proteins were activated as a survival mechanism, whereas the predominant pathway of death was p53-mediated apoptosis.