Microwave-Assisted Atom Transfer Radical Cyclization in the Synthesis of 3,3-Dichloro-γ- and δ-Lactams from N-Alkenyl-Tethered Trichloroacetamides Catalyzed by RuCl2(PPh3)3 and Their Cytotoxic Evaluation.

An expeditious synthesis of γ- and δ-lactams from tethered alkenyl trichloroacetamides in the presence of 5% of RuCl2(PPh3)3 is reported. In this investigation we have demonstrated that microwave activation significantly enhances reaction rates, leading to the formation of the corresponding lactams in yields ranging from good to excellent. Thus, we have been able to prepare a wide range of lactams, including indole and morphan bicyclic scaffolds, where the corresponding reactions were completely diastereoselective. This process was successfully extended to α,α-dichloroamides without affecting either their yield or their diastereoselectivity. Some of the lactams prepared in this work were evaluated for their hemolytic and cytotoxic responses. All compounds were found to be non-hemolytic at the tested concentration, indicating their safety profile in terms of blood cell integrity. Meanwhile, they exhibited interesting cytotoxicity responses that depend on both their lactam structure and cell line. Among the molecules tested, γ-lactam 2a exhibited the lowest IC50 values (100-250 µg/mL) as a function of its cell line, with promising selectivity against squamous carcinoma cells (A431) in comparison with fibroblasts (3T3 cell line).

Insight into the Antioxidant Activity of Ascorbic Acid-Containing Gelatin Nanoparticles in Simulated Chronic Wound Conditions.

Chronic wounds differ from acute wounds by remaining in the inflammatory phase for a long time. This chronic inflammation confers a high concentration of inflammatory cytokines, proteases, and ROS. Likewise, the pH environment of chronic wounds has been recorded within the range of 7.2-8.9 due to the alkaline by-products of bacterial proliferation. In this work, differences in pH between healthy skin and chronic cutaneous wounds have been used for the design and development of pH-responsive gelatin-based nanoparticles (NPs). Ascorbic acid (AA), as an antioxidant compound that can neutralize reactive oxygen species (ROS), has been the therapeutic model compound included in these NPs. The goal of the present work has been the preparation and characterization (physicochemical and biological properties) of NPs for the effective release of AA under simulated chronic wound conditions. In vitro experiments demonstrated total AA release at pH corresponding to the chronic wounds. The biocompatible character of these gelatin-based NPs based on their hemolytic and cytotoxicity responses has been highlighted under in vitro conditions. The reversible and protective antioxidant properties of the AA-including NPs in erythrocytes and skin cell lines, respectively, have been confirmed to be modulated by the gelatin A gel strength.

Arginine Gemini-Based Surfactants for Antimicrobial and Antibiofilm Applications: Molecular Interactions, Skin-Related Anti-Enzymatic Activity and Cytotoxicity.

The antimicrobial and antibiofilm properties of arginine-based surfactants have been evaluated. These two biological properties depend on both the alkyl chain length and the spacer chain nature. These gemini surfactants exhibit good activity against a wide range of bacteria, including some problematic resistant microorganisms such us methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa. Moreover, surfactants with a C10 alkyl chain and C3 spacer inhibit the (MRSA) and Pseudomonas aeruginosa biofilm formation at concentrations as low as 8 µg/mL and are able to eradicate established biofilms of these two bacteria at 32 µg/mL. The inhibitory activities of the surfactants over key enzymes enrolled in the skin repairing processes (collagenase, elastase and hyaluronidase) were evaluated. They exhibited moderate anti-collagenase activity while the activity of hyaluronidase was boosted by the presence of these surfactants. These biological properties render these gemini arginine-based surfactants as perfect promising candidates for pharmaceutical and biological properties.

Spheroid Formation and Recovery Using Superhydrophobic Coating for Regenerative Purposes.

Cell therapies commonly pursue tissue stimulation for regenerative purposes by replacing cell numbers or supplying for functional deficiencies. To this aim, monodispersed cells are usually transplanted for incorporation by local injection. The limitations of this strategy include poor success associated with cell death, insufficient retention, or cell damage due to shear forces associated with the injection. Spheroids have recently emerged as a model that mimics an in vivo environment with more representative cell-to-cell interactions and better intercellular communication. Nevertheless, cost-effective and lab friendly fabrication and effectively performed recovery are challenges that restrict the broad application of spheroids. In this work, glass surfaces were modified with an environmentally friendly superhydrophobic coating. The superhydrophobic surfaces were used for the 3D spheroid preparation of fibroblasts (3T3 cell line) and keratinocytes (HaCaT cell line). The effectiveness of the spheroids to be recovered and grown under 2D culture conditions was evaluated. The morphology of the migrated cells from the 3D spheroids was characterized at the nano-microscale through 3D profilometry. The results demonstrated improved adhesion and proliferation in the migrated cells, both advanced properties for regenerative applications.

Ceratonia siliqua L. Pod Extract: From Phytochemical Characterization to Liposomal Formulation and Evaluation of Behaviour in Cells.

The formulation of plant extracts in phospholipid vesicles is a promising strategy to exploit their biological properties while solving problems related to poor solubility in water, high instability, and low skin permeation and retention time. In this study, Ceratonia siliqua ripe pods were used for the preparation of a hydro-ethanolic extract, which showed antioxidant properties owing to the presence of biologically active compounds identified by liquid chromatography-mass spectrometry (e.g., hydroxybenzoic acid and flavonoid derivatives). To improve the applicability of the extract in therapy, a topical formulation based on liposomes was explored. The vesicles were characterized by small size (around 100 nm), negative charge (-13 mV), and high entrapment efficiency (>90%). Furthermore, they displayed both spherical and elongated shapes, with oligolamellar structure. Their biocompatibility was demonstrated in cells, including erythrocytes and representative skin cell lines. The antioxidant activity of the extract was proved by the scavenging of free radicals, the reduction of ferric ions, and the protection of skin cells from oxidative damage.

Phenolic Fingerprint, Bioactivity and Nanoformulation of Prunus spinosa L. Fruit Extract for Skin Delivery.

The nanoformulation of plant extracts in phospholipid vesicles is a promising strategy to exploit the biological properties of natural bioactive substances and overcome drawbacks such as poor aqueous solubility, chemical instability, low skin permeation and retention time, which strongly limit their topical application. In this study, Prunus spinosa berries were used for the preparation of a hydro-ethanolic extract, which showed antioxidant and antibacterial properties owing to the presence of phenolic compounds. Two types of phospholipid vesicles were developed to improve the applicability as topical formulations. Liposomes and Penetration Enhancer-containing Vesicles were characterized for mean diameter, polydispersity, surface charge, shape, lamellarity, and entrapment efficiency. Additionally, their safety was assayed with different cell models, including erythrocytes and representative skin cell lines.

Cytotoxic Assessment of 3,3-Dichloro-ß-Lactams Prepared through Microwave-Assisted Benzylic C-H Activation from Benzyl-Tethered Trichloroacetamides Catalyzed by RuCl2(PPh3)3.

Natural and synthetic ß-lactam derivatives constitute an interesting class of compounds due to their diverse biological activity. Mostly used as antibiotics, they were also found to have antitubercular, anticancer and antidiabetic activities, among others. In this investigation, six new 3,3-dichloro-ß-lactams prepared in a previous work were evaluated for their hemolytic and cytotoxic properties. The results showed that the proposed compounds have non-hemolytic properties and exhibited an interesting cytotoxic activity toward squamous cell carcinoma (A431 cell line), which was highly dependent on the structure and concentration of these ß-lactams. Among the molecules tested, 2b was the most cytotoxic, with the lowest IC50 values (30-47 µg/mL) and a promising selectivity against the tumor cells compared with non-tumoral cells.

Satisfacción de la población atendida por los posgradistas de medicina familiar y comunitaria del centro de salud primavera 2. Año 2021 / Satisfaction of the population served by the postgraduate students of family and community medicine at the primavera 2 health center. year 2021

El nivel de satisfacción de la población atendida por los médicos posgradistas de Medicina Familiar y Comunitaria cobra importancia por ser el eje fortalecedor del primer nivel de atención complementando la atención primaria de salud. Objetivo: Describir el nivel de satisfacción de la población atendida por los posgradistas de Medicina Familiar y Comunitaria en el Centro de Salud Primavera 2 en el año 2021. Materiales y Métodos: Se realizó un estudio observacional de corte transversal, mediante muestreo aleatorio simple probabilístico se seleccionaron a 350 personas que fueron atendidas. Resultados: El 91,7% de la población expresó que el proceso de atención fue entre excelente y buena, el 89,1% manifestó que la relación médico paciente es satisfactoria, además se encontró que la satisfacción global es muy satisfactorio y medianamente satisfactorio con el 82,9% y el 16% respectivamente. Conclusiones: Las actividades académicas, la falta de medicamentos, la estrechez de los tiempos asignados en la atención y las limitaciones en el proceso de atención ocasionadas por la pandemia de Covid-19, probablemente influyeron en los resultados de insatisfacción de la investigación(AU)

the level of satisfaction of the population attended by postgraduate doctors of Family and Community Medicine becomes important for being the strengthening axis of the first level of care complementing primary health care. Objective: to describe the level of satisfaction of the population served by postgraduate students in Family and Community Medicine in the Primavera 2 Health Center in the year 2021. Materials and Methods: a study was carried out cross-sectional observational study, through probabilistic simple random sampling, they selected 350 people who were attended. Results: 91.7% of the population expressed that the care process was between excellent and good, 89.1% stated that the doctor-patient relationship is satisfactory, it was also found that global satisfaction is very satisfactory and moderately satisfactory with 82.9% and 16% respectively. Conclusions: the academic activities, the lack of medicines, the narrowness of the times assigned in care and the limitations in the care process caused by the pandemic of Covid-19, probably influenced the dissatisfaction results of the investigation(AU)

Enhanced performance of gelatin 5-fluorouracil-containing nanoparticles against squamous cell carcinoma in simulated chronic wounds conditions.

Chronic wounds are considered a silent epidemic affecting a significant fraction of the World population. Their treatment supposes a large fraction of the public spending on the health of developed countries. In chronic wounds secondary to burns, trauma, UV light radiation, and diabetes, among others, the development of squamous cell carcinoma (SCC) has been reported. If detected early, 95% of SCC are most comfortable to be treated and cured; however, 5% of advanced SCC is more dangerous and challenging to treat. It has been reported that the pH value within the wound-milieu influences indirectly and directly all biochemical reactions taking place in this process of healing. Differences in pH values between normal skin and chronic cutaneous wounds could be considered in designing and developing stimuli-responsive nanomaterials. In this work, the anticancer drug 5-fluorouracil (5-FU) inclusion on gelatin-based NPs for SCC treatment has been projected. The present work goal is to prepare and characterize physicochemical and biological properties of new therapeutic-containing NPs for the sustainable delivery of 5-FU under simulated chronic wound conditions. In vitro experiments have been performed to assess the biocompatible character of these gelatin-based NPs in terms of their hemolytic and cytotoxicity properties. Due to hyperglycemia impact on both the chronicity of the wounds and chemotherapy efficacy, cellular responses have been determined under euglycemic and hyperglycemic conditions. In vitro cytotoxicity studies have reported good selective toxicity against the A431 cell line, demonstrating that gelatin-based NPs are promising dual-responsive delivery systems to SCC targeting under simulated chronic wound conditions.

Oil-in-water nanoemulsions are suitable for carrying hydrophobic compounds: Indomethacin as a model of anti-inflammatory drug.

Oil-in-water nanoemulsions are increasingly being used as delivery systems for encapsulating lipophilic components in functional food, personal care and pharmaceutical products. In the current study, we developed a multimodal platform to carry hydrophobic indomethacin or magnetic nanoparticles, or both. As a consequence, this platform has great potential for therapeutic or imaging purposes. By optimizing the system composition and homogenization conditions, a nanoemulsion with a mean droplet diameter of about 200nm and a low polydispersity index (<0.2) was formed. The plain nanoemulsion was shown to be innocuous in cellular studies and did not present acute toxicity (observed in a rat model). More interesting was the finding that nanoemulsions loaded with indomethacin presented a significantly different anti-inflammatory than the free drug.

Inclusion of a single-tail amino acid-based amphiphile in a lipoplex formulation: effects on transfection efficiency and physicochemical properties.

Effects of the addition of a cationic amino acid-based synthetic amphiphile, arginine N-lauroyl amide dihydrochloride (ALA), to a lipid-based transfection formulation have been investigated. It is shown that the inclusion of ALA results in a substantial enhancement of the transfection capability of lipoplexes prepared with liposomes of 1-palmitoyl-2-oleoyl-sn-glycero-3-ethylphosphocholine and cholesterol, which themselves mediate highly efficient transfection. A possible explanation for the increased biological activity is that ALA adsorbed to the surface of the DNA-lipid complexes is involved in triggering internalization. However, in order to identify possible additional factors underlying the enhanced transfection efficiency, the physical properties of formulations with and without ALA were characterized using cryo-transmission electron microscopy, dynamic light scattering, and an ethidium bromide intercalation assay. ALA seems to have limited influence on the initial internal structure of the complexes and the protection of DNA, but its presence is found to decrease the average effective size of the dispersed particles; this change in size may be important in improving the biological activity. Furthermore, ALA can act to influence the transfection efficiency of the formulation by promoting the release of DNA following internalization in the transfected cells.