The Antitumoral Effect In Ovo of a New Inclusion Complex from Dimethoxycurcumin with Magnesium and Beta-Cyclodextrin.

Breast cancer is one of the leading causes of death in the female population because of the resistance of cancer cells to many anticancer drugs used. Curcumin has cytotoxic activities against breast cancer cells, although it has limited use due to its poor bioavailability and rapid metabolic elimination. The synthesis of metal complexes of curcumin and curcuminoids is a relevant topic in the search for more active and selective derivatives of these molecular scaffolds. However, solubility and bioavailability are concomitant disadvantages of these types of molecules. To overcome such drawbacks, the preparation of inclusion complexes offers a chemical and pharmacologically safe option for improving the aqueous solubility of organic molecules. Herein, we describe the preparation of the inclusion complex of dimethoxycurcumin magnesium complex (DiMeOC-Mg, (4)) with beta-cyclodextrin (DiMeOC-Mg-BCD, (5)) in the stoichiometric relationship 1:1. This new inclusion complex's solubility in aqueous media phosphate buffer saline (PBS) was improved by a factor of 6x over the free metal complex (4). Furthermore, 5 affects cell metabolic rate, cell morphology, cell migration, induced apoptosis, and downregulation of the matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), interleukin-6 (IL-6), and signal transducer and activator of transcription-3 (STAT3) expression levels on MD Anderson metastasis breast-231 cancer (MDA-MB-231) cell lines. Results of an antitumor assay in an in ovo model showed up to 30% inhibition of tumor growth for breast cancer (MDA-MB-231) when using (5) (0.650 mg/kg dose) and 17.29% inhibition with the free homoleptic metal complex (1.5 mg/kg dose, (4)). While the formulation of inclusion complexes from metal complexes of curcuminoids demonstrates its usefulness in improving the solubility and bioavailability of these metallodrugs, the new compound (5) exhibits excellent potential for use as a therapeutic agent in the battle against breast cancer.

Perfectionism as a Paradoxical Factor in Sport and Exercise Performance: An Umbrella Review.

Objective: Traditionally, perfectionism has been regarded as a commendable trait in the realm of sports and exercise. However, recent research has uncovered a paradoxical aspect of perfectionism in these domains. This umbrella review seeks to offer a comprehensive overview of the intricate role that perfectionism plays in sport and exercise performance. Method : As an umbrella review, we systematically explored three widely used scientific databases-PubMed, Scopus, and ISI-to identify relevant systematic reviewes and meta-analyses investigating the relationship between perfectionism and sports performance. Results: After careful evaluation, eight studies met our inclusion criteria and were included in the study. These eight eligible studies comprised five systematic reviews and three systematic review and meta-analysis publications. These publications have explored the correlation between perfectionism and sports performance in teenager and adult populations, as well as professional and amateur athletes. Most of the original articles included in these studies had a cross-sectional design and some of them were longitudinal research. All reviewed articles reported a significant correlation between perfectionism and sports performance, regardless of gender and age. In general, the main consensus of these studies is a moderate to high positive correlation between perfectionistic strivings and sports performance, as well as a moderate to high negative correlation between perfectionistic concerns and sports performance. Conclusion: In summary, perfectionism exhibits both positive and negative effects on athlete outcomes. Maladaptive perfectionism is linked to adverse consequences, while adaptive perfectionism can yield positive effects. Promisingly, psychological interventions such as mindfulness-based approaches and ACT-based interventions show potential in reducing perfectionism and enhancing athlete outcomes. Future research should delve deeper into the intricate relationship between perfectionism and athlete performance and continue to devise interventions that counteract the detrimental effects of perfectionistic tendencies.

Family functioning in students of health sciences in four Latin American countries: a study of the structure and factorial invariance of the FACES III scale. A cross-sectional study.

BACKGROUND: Psychometric studies of the FACES III scale in Spanish-speaking countries show a lack of agreement on the factorial structure of the scale. In addition, most of the studies have only performed exploratory analyses of its factorial structure. OBJECTIVE: The objective of the present study was to confirm the structure and factorial invariance of the FACES III scale in nursing and obstetric students from Chile, Colombia, Peru, and Mexico. METHODS: A total of 3303 students from the four countries participated in this study (Colombia = 1559, Chile = 1224, Peru = 215, Mexico = 305). RESULTS: The results of the study showed that the Bi-factor model presents the best-fit indexes to the data from Colombia, Chile, and Mexico, but not from Peru. In addition, it was found that this model showed evidence of being strictly invariant among the three countries in the sequence of the invariance models proposed: metric invariance (ΔRMSEA = .000), scalar (ΔRMSEA = .008), and strict (ΔRMSEA = .008). The bi-factor model also showed adequate reliability indexes in the three countries. CONCLUSION: It is concluded that the FACES III scale shows adequate psychometric performance under a bi-factor model in nursing and obstetric students from Colombia, Chile, and Mexico. The lack of fit of the model in Peru could be associated with the small sample size.

Evaluation of the psychometric properties of the family adaptability and cohesion scale (FACES III) through item response theory models in students from Chile and Colombia.

BACKGROUND: A psychometric study of the Family Adaptability and Cohesion Scale (FACES III) has been conducted in Spanish-speaking countries from the perspective of the classical test theory. However, this approach has limitations that affect the psychometric understanding of this scale. OBJECTIVE: Accordingly, this study used the item response theory to investigate the psychometric performance of the items. Furthermore, it evaluated the differential performance of the items for Colombia and Chile. METHOD: For this purpose, 518 health science students from both countries participated. Confirmatory Factor Analysis was used. RESULTS: The study results revealed that the cohesion and adaptability items presented adequate discrimination and difficulty indices. In addition, items 5, 8, 13, 17, and 19 of cohesion indicated differential functioning between students from both countries, with Chilean students exhibiting a greater discriminatory power. Further, the Colombian group exhibited a greater discriminatory power for item 18 of adaptability. CONCLUSIONS: The study concluded that the items of FACES III indicated adequate psychometric performance in terms of their discriminative capacity and difficulty in Chile and Colombia.

First Gallium and Indium Crystal Structures of Curcuminoid Homoleptic Complexes: All-Different Ligand Stereochemistry and Cytotoxic Potential.

The crystal structure determination of metal complexes of curcuminoids is a relevant topic to assess their unequivocal molecular structure. We report herein the first two X-ray crystal structures of homoleptic metal complexes of a curcuminoid, namely Dimethoxycurcumin (DiMeOC), with gallium and indium. Such successful achievement can be attributed to the suppression of interactions from the phenolic groups, which favor an appropriate molecular setup, rendering Dimethoxycurcumin gallium ((DiMeOC)2-Ga) and Dimethoxycurcumin indium ((DiMeOC)3-In) crystals. Surprisingly, the conformation of ligands in the crystal structures shows differences in each metal complex. Thus, the ligands in the (DiMeOC)2-Ga complex show two different conformers in the two molecules of the asymmetric unit. However, the ligands in the (DiMeOC)3-In complex exhibit three different conformations within the same molecule of the asymmetric unit, constituting the first such case described for an ML3 complex. The cytotoxic activity of the (DiMeOC)2-Ga complex is 4-fold higher than cisplatin against the K562 cell line and has comparable activity towards U251 and PC-3 cell lines. Interestingly, this complex exhibit three times lesser toxicity than cisplatin and even slightly lesser cytotoxicity than curcumin itself.

The Homoleptic Curcumin-Copper Single Crystal (ML2): A Long Awaited Breakthrough in the Field of Curcumin Metal Complexes.

The first single crystal structure of the homoleptic copper (II) ML2 complex (M=Cu (II), L = curcumin) was obtained and its structure was elucidated by X-ray diffraction showing a square planar geometry, also confirmed by EPR. The supramolecular arrangement is supported by C-H···O interactions and the solvent (MeOH) plays an important role in stabilizing the crystal packing Crystallinity was additionally assessed by XRD patterns. The log P value of the complex (2.3 ± 0.15) was determined showing the improvement in water solubility. The cytotoxic activity of the complex against six cancer cell lines substantially surpasses that of curcumin itself, and it is particularly selective against leukemia (K562) and human glioblastoma (U251) cell lines, with similar antioxidant activity to BHT. This constitutes the first crystal structure of pristine curcumin complexed with a metal ion.

Perezone and its phenyl glycine derivative induce cytotoxicity via caspases on human glial cancer cells.

The new phenyl glycine derivative of perezone was obtained in a single reaction step in ca. 80% yield which showed remarkable cytotoxic activity against the astrocytoma U-251 cell line. After 24 h of exposure, both perezone (IC50 = 6.83 ± 1.64 µM) and its phenyl glycine derivative (2.60 ± 1.69 µM) showed cytotoxic effect on U-251 cells but were five times less cytotoxic on the non-tumoral SVGp12 cell line (IC50 = 28.54 ± 1.59 and 31.87 ± 1.54 µM respectively). Both compounds induced cellular morphological changes (pyknosis or cytoplasmic vacuolization) and increased the expression of caspases 3, 8, and 9 genes related to apoptosis. In the acute toxicity study, phenyl glycine perezone (DL50 = 2000 mg/Kg) demonstrated to be less toxic than perezone (DL50 = 500 mg/Kg). Phenylglycine-perezone can envisage a beneficial therapeutic potential.

Three new coordination geometries of homoleptic Zn complexes of curcuminoids and their high antiproliferative potential.

To our previously reported first crystal structure of a homoleptic zinc curcuminoid complex with square pyramidal geometry, we add herein three new geometries of homoleptic type complexes i.e. octahedral, trigonal-pyramidal, and trigonal-bipyramidal. Octahedral geometry was observed in the new pseudo-polymorph of the DAC-Zn complex resulting from crystallization in DMF, while square-pyramidal geometry was obtained in DMSO. Improving crystallinity involved suppressing the phenolic interactions by etherification and esterification. The complete characterization of these complexes was carried out using SCXRD, IR, MS, EA, liquid, and solid-state NMR. Moreover, the cytotoxic activity of all complexes was evaluated. The IC50 values for the DiMeOC-Zn (7) complex were 8 or 22 times higher than for cisplatin in the U251 and HCT-15 cell lines, indicating a high antiproliferative and therapeutic potential.

Homoleptic Complexes of Heterocyclic Curcuminoids with Mg(II) and Cu(II): First Conformationally Heteroleptic Case, Crystal Structures, and Biological Properties.

We report herein the synthesis and characterization of three heterocyclic curcuminoid ligands and their homoleptic metal complexes with magnesium and copper. Thus, N-methyl-2-pyrrolecarboxaldehyde, Furan-2-carboxaldehyde, and 2-Thiophenecarboxaldehyde were condensed with 2,4-pentanedione-boron trioxide complex. The first N-methyl-2-pyrrole curcuminoid and its Mg(II) complex are reported. All curcuminoid ligands and their corresponding metal complexes were characterized by infrared spectroscopy (IR), liquid state nuclear magnetic resonance (LSNMR), electron paramagnetic resonance (EPR), mass spectrometry (MS) and single crystal X-ray diffraction (SCXRD). The ThiopheneCurc-Cu (9) constitutes the first case of a "conformationally-heteroleptic" complex. The unique six-peaks star arrangement for the ThiopheneCurc ligand derived from the supramolecular description is reported. The metal complexes of FuranCurc-Mg (5) and ThiopheneCurc-Cu (9) have a good antioxidant effect (IC50 = 11.26 ± 1.73 and 10.30 ± 0.59 µM), three and two times higher than their free ligands respectively. Additionally, (5) shows remarkable cytotoxicity against colon cancer adenocarcinoma cell line HCT-15, comparable to that of cisplatin, with a negligible toxic effect in vitro towards a healthy monkey kidney cell line (COS-7).

Development of a Simulation Software Algorithm for High-End Mechanical Ventilators with Functionalities to attend COVID-19 Patients.

More than 500 millions of people were affected by the COVID-19 pandemic and in Peru there is an increasing the high numbers of cumulative cases; as well as the hospitalized people, where more than 20 % require mechanical ventilation. This condition with other respiratory diseases cause patients to remain connected to a mechanical ventilator until they regain the ability to perform this vital function on their own. Some prototypes with characteristics equivalent to a high-end mechanical ventilator have been developed. And therefore, this paper presents the design and simulation of an algorithm for the pressure-controlled pulmonary ventilation mode of the mechanical ventilator. The functional design of the algorithm uses the linear multi compartment mathematical model to simulate the respiratory system. Finally the results respond adequately under multiple scenarios, including variations of the ventilator and pulmonary parameters, where the algorithm presents encouraging results in the mechanical ventilator simulation. Clinical relevance - The algorithm presented in this study will allow to have better knowledge for a treatment and eventual clinical diagnosis in health centers, especially in eventual variants and outbreaks of COVID-19.

High Yield Synthesis of Curcumin and Symmetric Curcuminoids: A "Click" and "Unclick" Chemistry Approach.

The worldwide known and employed spice of Asian origin, turmeric, receives significant attention due to its numerous purported medicinal properties. Herein, we report an optimized synthesis of curcumin and symmetric curcuminoids of aromatic (bisdemethoxycurcumin) and heterocyclic type, with yields going from good to excellent using the cyclic difluoro-boronate derivative of acetylacetone prepared by reaction of 2,4-pentanedione with boron trifluoride in THF (ca. 95%). The subsequent cleavage of the BF2 group is of significant importance for achieving a high overall yield in this two-step procedure. Such cleavage occurs by treatment with hydrated alumina (Al2O3) or silica (SiO2) oxides, thus allowing the target heptanoids obtained in high yields as an amorphous powder to be filtered off directly from the reaction media. Furthermore, crystallization instead of chromatographic procedures provides a straightforward purification step. The ease and efficiency with which the present methodology can be applied to synthesizing the title compounds earns the terms "click" and "unclick" applied to describe particularly straightforward, efficient reactions. Furthermore, the methodology offers a simple, versatile, fast, and economical synthetic alternative for the obtention of curcumin (85% yield), bis-demethoxycurcumin (78% yield), and the symmetrical heterocyclic curcuminoids (80-92% yield), in pure form and excellent yields.

A Suite of Mobile Conversational Agents for Daily Stress Management (Popbots): Mixed Methods Exploratory Study.

BACKGROUND: Approximately 60%-80% of the primary care visits have a psychological stress component, but only 3% of patients receive stress management advice during these visits. Given recent advances in natural language processing, there is renewed interest in mental health chatbots. Conversational agents that can understand a user's problems and deliver advice that mitigates the effects of daily stress could be an effective public health tool. However, such systems are complex to build and costly to develop. OBJECTIVE: To address these challenges, our aim is to develop and evaluate a fully automated mobile suite of shallow chatbots-we call them Popbots-that may serve as a new species of chatbots and further complement human assistance in an ecosystem of stress management support. METHODS: After conducting an exploratory Wizard of Oz study (N=14) to evaluate the feasibility of a suite of multiple chatbots, we conducted a web-based study (N=47) to evaluate the implementation of our prototype. Each participant was randomly assigned to a different chatbot designed on the basis of a proven cognitive or behavioral intervention method. To measure the effectiveness of the chatbots, the participants' stress levels were determined using self-reported psychometric evaluations (eg, web-based daily surveys and Patient Health Questionnaire-4). The participants in these studies were recruited through email and enrolled on the web, and some of them participated in follow-up interviews that were conducted in person or on the web (as necessary). RESULTS: Of the 47 participants, 31 (66%) completed the main study. The findings suggest that the users viewed the conversations with our chatbots as helpful or at least neutral and came away with increasingly positive sentiment toward the use of chatbots for proactive stress management. Moreover, those users who used the system more often (ie, they had more than or equal to the median number of conversations) noted a decrease in depression symptoms compared with those who used the system less often based on a Wilcoxon signed-rank test (W=91.50; Z=-2.54; P=.01; r=0.47). The follow-up interviews with a subset of the participants indicated that half of the common daily stressors could be discussed with chatbots, potentially reducing the burden on human coping resources. CONCLUSIONS: Our work suggests that suites of shallow chatbots may offer benefits for both users and designers. As a result, this study's contributions include the design and evaluation of a novel suite of shallow chatbots for daily stress management, a summary of benefits and challenges associated with random delivery of multiple conversational interventions, and design guidelines and directions for future research into similar systems, including authoring chatbot systems and artificial intelligence-enabled recommendation algorithms.

Multicomponent synthesis and anti-proliferative screening of biaryl triazole-containing cyclophanes.

We report a practical two-step approach involving a Ugi 4-CR/ azide-alkyne cycloaddition for the synthesis of biaryl-containing cyclophanes. The series represents an extension of our previously reported macrocycles as an effort to enhance the anti-proliferative activity of this scaffold. In this variant, we incorporate a biphenyl moiety in the framework, thus enhancing the macrocycle size, lipophilicity, and structural diversity. Macrocycles were tested against different cell lines, being more cytotoxic against prostate (PC-3 and DU-145) and breast (MCF-7) tumor cells. Gratifyingly, the most active compound showed a significative enhancement of PC-3 growth inhibition with respect to our previous series, reaffirming the potential anti-proliferative activity of this kind of cyclophanes.

Non-Cytotoxic Dibenzyl and Difluoroborate Curcuminoid Fluorophores Allow Visualization of Nucleus or Cytoplasm in Bioimaging.

Curcumin, the most important secondary metabolite isolated from Curcuma longa, is known for its numerous purported therapeutic properties and as a natural dye. Herein, based on curcumin's intrinsic fluorescence, a search for improved curcumin-based fluorophores was conducted. Within the set of semi-synthetic curcumin derivatives i.e. mono (1), di (2), tri (3), tetra (4) benzylated and dibenzyl-fluoroborate (5), the fluorescence properties of 2 and 5 in solution outstood with a two-fold quantum yield compared to curcumin. Furthermore, all benzylated derivatives showed a favorable minimal cytotoxic activity upon screening at 25 µM against human cancer and non-tumoral COS-7 cell lines, with a reduction of its cytotoxic effect related to the degree of substitution. Fluorophores 2 and 5 are versatile bioimaging tools, as revealed by Confocal Fluorescence Microscopy (CFM), and showed permeation of living cell membranes of astrocytes and astrocytomas. When 2 is excited with a 405- (blue) or 543-nm (green) laser, it is possible to exclusively and intensively visualize the nucleus. However, the fluorescence emission fades as the laser wavelength moves towards the red region. In comparison, 5 allows selective visualization of cytoplasm when a 560-nm laser is used, showing emission in the NIR region, while it is possible to exclusively observe the nucleus at the blue region with a 405-nm laser.

Full Structural Characterization of Homoleptic Complexes of Diacetylcurcumin with Mg, Zn, Cu, and Mn: Cisplatin-level Cytotoxicity in Vitro with Minimal Acute Toxicity in Vivo.

At the present time, scientists place a great deal of effort worldwide trying to improve the therapeutic potential of metal complexes of curcumin and curcuminoids. Herein, the synthesis of four homoleptic metal complexes with diacetylcurcumin (DAC), using a ligand designed to prevent the interaction of phenolic groups, rendering metal complexes through the ß-diketone functionality, is reported. Due to their physiological relevance, we used bivalent magnesium, zinc, copper, and manganese for complexation with DAC. The resulting products were characterized by ultraviolet-visible (UV-Vis), fluorescence spectroscopy, infrared spectroscopy (IR), liquid and solid-state nuclear magnetic resonance (NMR), electron paramagnetic resonance (EPR), magnetic moment, mass spectrometry (MS), single crystal, and powder X-ray diffraction (SCXRD and PXRD). Crystallization was achieved in dimethylsulfoxide (DMSO) or N,N-dimethylformamide (DMF) as triclinic systems with space group P-1, showing the metal bound to the ß-diketone function, while the 1H-NMR confirmed the preference of the enolic form of the ligand. Single crystal data demonstrated a 1:2 metal:ligand ratio. The inhibition of lipid peroxidation was evaluated using the thiobarbituric acid reactive substance assay (TBARS). All four metal complexes (Mg, Zn, Cu, and Mn) exhibited good antioxidant effect (IC50 = 2.03 ± 0.27, 1.58 ± 0.07, 1.58 ± 0.15 and 1.24 ± 0.10 µM respectively) compared with butylated hydroxytoluene (BHT) and α-tocopherol. The cytotoxic activity in human cancer cell lines against colon adenocarcinoma (HCT-15), mammary adenocarcinoma (MCF-7), and lung adenocarcinoma (SKLU-1) was found comparable ((DAC)2Mg), or ca. 2-fold higher ((DAC)2Zn) than cisplatin. The acute toxicity assays indicate class 5 toxicity, according to the Organization for Economic Co-operation and Development (OECD) guidelines at doses of 3 g/kg for all complexes. No mortality or changes in the behavior of animals in any of the treated groups was observed. A therapeutic potential can be envisaged from the relevant cytotoxic activity upon human cancer cell lines in vitro and the undetected in vivo acute toxicity of these compounds.

A New Family of Homoleptic Copper Complexes of Curcuminoids: Synthesis, Characterization and Biological Properties.

We report herein the synthesis and crystal structures of five new homoleptic copper complexes of curcuminoids. The scarcity of reports of homoleptic complex structures of curcuminoids is attributed to the lack of crystallinity of such derivatives, and therefore, their characterization by single crystal X-ray diffraction is rare. The ligand design suppressing the phenolic interaction by esterification or etherification has afforded a significant increase in the number of known crystal structures of homoleptic metal complexes of curcuminoids revealing more favorable crystallinity. The crystal structures of the present new copper complexes show four-fold coordination with a square planar geometry. Two polymorphs were found for DiBncOC-Cu when crystallized from DMF. The characterization of these new complexes was carried out using infrared radiation (IR), nuclear magnetic resonance (NMR), electron paramagnetic resonance (EPR), and single crystal X-ray diffraction (SCXRD) and the antioxidant and cytotoxic activity of the obtained complexes was evaluated.

Diversity-oriented synthesis and cytotoxic activity evaluation of biaryl-containing macrocycles.

Synthesis of biaryl-containing macrocycles has been carried out through a four-step approach comprising two Ugi four component reactions and a Suzuki-Miyaura macrocyclization. This protocol allowed the synthesis of 12- and 14-membered macrocycles. Cytotoxic activity evaluation showed that some of the molecules were effective against leukemia, glioblastoma and lung cancer cell lines (IC50 = 4.0, 5.9 and 7.6, respectively).

The influence of sulfur configuration in 1 H NMR chemical shifts of diasteromeric five-membered cyclic sulfites.

The effect of the stereochemistry of the sulfur atom on 1 H chemical shifts of the diasteromeric pair of cyclic sulfites of 4-[methoxy(4-nitrophenyl)methyl]-5-phenyl-1,3,2-dioxathiolan-2-oxide was investigated. The complete 1 H and 13 C NMR spectral assignment was achieved by the use of one-dimensional and two-dimensional NMR techniques in combination with X-ray data. A correlation of experimental data with theoretical calculations of chemical shift tensors using density functional theory and topological theory of atoms in molecules was made. Copyright © 2016 John Wiley & Sons, Ltd.