Vasopressin in the lateral septum decreases conditioned place preference to amphetamine and nucleus accumbens dopamine release.

The lateral septum (LS) is a limbic nucleus interconnected with several brain areas involved in the regulation of mood and reward. Vasopressin (AVP) is a neuropeptide that has been related to the effects of drugs of abuse, but its role in the addictive process is poorly understood. LS expresses a high density of AVP 1A receptors (V1A ). The aim of this work was to examine whether the modulation of LS AVP system affects the behavioral and neurochemical responses to amphetamine (AMPH) in male rats. Our results show that AMPH-induced conditioned place preference (CPP) produces a decrease in LS AVP content. Besides, we demonstrate that the microinjection of AVP in the LS impairs the expression of AMPH-induced CPP and that this effect is mediated by the activation of the V1A receptor in the LS. AVP microinjection in the LS elicited a decrease in neuronal activity in the nucleus accumbens (NAc) in animals subjected to AMPH conditioning. Finally, AVP microinjection in the LS decreased dopamine (DA) release in the NAc. Overall, our data demonstrate that intra-LS AVP diminishes the expression of AMPH conditioning behavior while decreasing neuronal activity and DA release in the NAc. Presumably, the effects of AVP in the LS produce an inhibition of GABAergic projections to the VTA, increasing local inhibitory tone in this nucleus, which in turn reduces the activity of DA projections to NAc. Thus, these results contribute to the knowledge about the role of AVP in LS in regulating the reward circuit and addictive like behaviors.

Poly-3-hydroxybutyrate-silver nanoparticles membranes as advanced antibiofilm strategies for combatting peri-implantitis.

Dental implant success is threatened by peri-implantitis, an inflammation leading to implant failure. Conventional treatments struggle with the intricate microbial and host factors involved. Antibacterial membranes, acting as barriers and delivering antimicrobials, may offer a promising solution. Thus, this study highlights the potential of developing antibacterial membranes of poly-3-hydroxybutyrate and silver nanoparticles (Ag Nps) to address peri-implantitis challenges, discussing design and efficacy against potential pathogens. Electrospun membranes composed of PHB microfibers and Ag Nps were synthesized in a blend of DMF/chloroform at three different concentrations. Various studies were conducted on the characterization and antimicrobial activity of the membranes. The synthesized Ag Nps ranged from 4 to 8 nm in size. Furthermore, Young's modulus decreased, reducing from 13.308 MPa in PHB membranes without Ag Nps to 0.983 MPa in PHB membranes containing higher concentrations of Ag Nps. This demonstrates that adding Ag Nps results in a less stiff membrane. An increase in elongation at break was noted with the rise in Ag Nps concentration, from 23.597 % in PHB membranes to 60.136 % in PHB membranes loaded with Ag Nps. The antibiotic and antibiofilm activity of the membranes were evaluated against Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus mutans, and Candida albicans. The results indicated that all PHB membranes containing Ag Nps exhibited potent antibacterial activity by inhibiting the growth of biofilms and planktonic bacteria. However, inhibition of C. albicans occurred only with the PHB-Ag Nps C membrane. These findings emphasize the versatility and potential of Ag Nps-incorporated membranes as a multifunctional approach for preventing and addressing microbial infections associated with peri-implantitis. The combination of antibacterial and antibiofilm properties in these membranes holds promise for improving the management and treatment of peri-implantitis-related complications.

Co-Encapsulation of Curcumin and α-Tocopherol in Bicosome Systems: Physicochemical Properties and Biological Activity.

A novel co-encapsulation system called bicosomes (bicelles within liposomes) has been developed to overcome the limitations associated with the topical application of curcumin (cur) and α-tocopherol (α-toc). The physicochemical properties and biological activity in vitro of bicosome systems were evaluated. Bicelles were prepared with DPPC, DHPC, cur, and α-toc (cur/α-toc-bicelles). Liposomal vesicles loading cur/α-toc-bicelles were prepared with Lipoid P-100 and cholesterol-forming cur/α-toc-bicosomes. Three cur/α-toc-bicosomes were evaluated using different total lipid percentages (12, 16, and 20% w/v). The results indicated that formulations manage to solubilize cur and α-toc in homogeneous bicelles < 20 nm, while the bicosomes reaches 303-420 nm depending on the total lipid percentage in the systems. Bicosomes demonstrated high-encapsulation efficiency (EE) for cur (56-77%) and α-toc (51-65%). The loading capacity (LC) for both antioxidant compounds was 52-67%. In addition, cur/α-toc-bicosomes decreased the lipid oxidation by 52% and increased the antioxidant activity by 60% compared to unloaded bicosomes. The cell viability of these cur/α-toc-bicosomes was >85% in fibroblasts (3T3L1/CL-173™) and ≥65% in keratinocytes (Ha-CaT) and proved to be hematologically compatible. The cur/α-toc-bicelles and cur/α-toc-bicosomes inhibited the growth of C. albicans in a range between 33 and 76%. Our results propose bicosome systems as a novel carrier able to co-encapsulate, solubilize, protect, and improve the delivery performance of antioxidant molecules. The relevance of these findings is based on the synergistic antioxidant effect of its components, its biocompatibility, and its efficacy for dermal tissue treatment damaged by oxidative stress or by the presence of C. albicans. However, further studies are needed to assess the efficacy and safety of cur/α-toc bicosomes in vitro and in vivo.

Osteoinductive Electrospun Scaffold Based on PCL-Col as a Regenerative Therapy for Peri-Implantitis.

Peri-implantitis is a serious condition affecting dental implants that can lead to implant failure and loss of osteointegration if is not diagnosed and treated promptly. Therefore, the development of new materials and approaches to treat this condition is of great interest. In this study, we aimed to develop an electrospun scaffold composed of polycaprolactone (PCL) microfibers loaded with cholecalciferol (Col), which has been shown to promote bone tissue regeneration. The physical and chemical properties of the scaffold were characterized, and its ability to support the attachment and proliferation of MG-63 osteoblast-like cells was evaluated. Our results showed that the electrospun PCL-Col scaffold had a highly porous structure and good mechanical properties. The resulting scaffolds had an average fiber diameter of 2-9 µm and high elongation at break (near six-fold under dry conditions) and elasticity (Young modulus between 0.9 and 9 MPa under dry conditions). Furthermore, the Col-loaded scaffold was found to decrease cell proliferation when the Col content in the scaffolds increased. However, cytotoxicity analysis proved that the PCL scaffold on its own releases more lactate dehydrogenase into the medium than the scaffold containing Col at lower concentrations (PCL-Col A, PCL-Col B, and PCL-Col C). Additionally, the Col-loaded scaffold was shown to effectively promote the expression of alkaline phosphatase and additionally increase the calcium fixation in MG-63 cells. Our findings suggest that the electrospun membrane loaded with Col can potentially treat peri-implantitis by promoting bone formation. However, further studies are needed to assess the efficacy and safety of this membrane in vivo.

Functionalizing Dendrimers for Targeted Delivery of Bioactive Molecules to Macrophages: A Potential Treatment for Mycobacterium tuberculosis Infection-A Review.

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis that replicates inside human alveolar macrophages. This disease causes significant morbidity and mortality throughout the world. According to the World Health Organization 1.4 million people died of this disease in 2021. This indicates that despite the progress of modern medicine, improvements in diagnostics, and the development of drug susceptibility tests, TB remains a global threat to public health. In this sense, host-directed therapy may provide a new approach to the cure of TB, and the expression of miRNAs has been correlated with a change in the concentration of various inflammatory mediators whose concentrations are responsible for the pathophysiology of M. tuberculosis infection. Thus, the administration of miRNAs may help to modulate the immune response of organisms. However, direct administration of miRNAs, without adequate encapsulation, exposes nucleic acids to the activity of cytosolic nucleases, limiting their application. Dendrimers are a family of highly branched molecules with a well-defined architecture and a branched conformation which gives rise to cavities that facilitate physical immobilization, and functional groups that allow chemical interaction with molecules of interest. Additionally, dendrimers can be easily functionalized to target different cells, macrophages among them. In this sense, various studies have proposed the use of different cell receptors as target molecules to aim dendrimers at macrophages and thus release drugs or nucleic acids in the cell of interest. Based on the considerations, the primary objective of this review is to comprehensively explore the potential of functionalized dendrimers as delivery vectors for miRNAs and other therapeutic agents into macrophages. This work aims to provide insights into the use of functionalized dendrimers as an innovative approach for TB treatment, focusing on their ability to target and deliver therapeutic cargo to macrophages.

One-step electrospun scaffold of dual-sized gelatin/poly-3-hydroxybutyrate nano/microfibers for skin regeneration in diabetic wound.

This work aimed to implement an electrospinning protocol that allows simultaneous production of micro- and nanofibers in a single scaffold to mimic the extracellular matrix (ECM) combining biodegradable polymers and proteins, and to evaluate its capability to manage diabetic wounds. Poly-3-hydroxybutyrate (PHB) and gelatin (Ge) were chosen to prepare micro- and nanofibers, respectively. Electrospinning conditions were optimized testing various polymer concentrations, voltages, and flow rates. One-step dual-size fibers were obtained from 8%w/v PHB in chloroform (microfibers, 1.25 ± 0.17 µm) and 30%w/v gelatin in acetic acid (75%w/v) (nanofibers, 0.20 ± 0.04 µm), at 0.5 mL/h and 25 kV. A chemical characterization, swelling, hydrophilicity of scaffolds made of PHB-microfibers, Ge-nanofibers and their combination (Ge-PHB) were evaluated before and after crosslinking with genipin. All scaffolds showed excellent fibroblasts viability and attachment after incubation for 1, 3, and 7 days, and low levels of hemolysis. In vivo wound healing was evaluated in diabetic rats for 21 days. Ge-containing scaffolds promoted faster healing. The wounds treated with the Ge-PHB scaffolds proved to be in a late proliferative stage showing higher content of hair follicles and sweat glands and lower content in fibroblast compared with the control wounds.

Genome-Wide Metabolic Reconstruction of the Synthesis of Polyhydroxyalkanoates from Sugars and Fatty Acids by Burkholderia Sensu Lato Species.

Burkholderia sensu lato (s.l.) species have a versatile metabolism. The aims of this review are the genomic reconstruction of the metabolic pathways involved in the synthesis of polyhydroxyalkanoates (PHAs) by Burkholderia s.l. genera, and the characterization of the PHA synthases and the pha genes organization. The reports of the PHA synthesis from different substrates by Burkholderia s.l. strains were reviewed. Genome-guided metabolic reconstruction involving the conversion of sugars and fatty acids into PHAs by 37 Burkholderia s.l. species was performed. Sugars are metabolized via the Entner-Doudoroff (ED), pentose-phosphate (PP), and lower Embden-Meyerhoff-Parnas (EMP) pathways, which produce reducing power through NAD(P)H synthesis and PHA precursors. Fatty acid substrates are metabolized via ß-oxidation and de novo synthesis of fatty acids into PHAs. The analysis of 194 Burkholderia s.l. genomes revealed that all strains have the phaC, phaA, and phaB genes for PHA synthesis, wherein the phaC gene is generally present in ≥2 copies. PHA synthases were classified into four phylogenetic groups belonging to class I II and III PHA synthases and one outlier group. The reconstruction of PHAs synthesis revealed a high level of gene redundancy probably reflecting complex regulatory layers that provide fine tuning according to diverse substrates and physiological conditions.

Influence of the carbon source on the properties of poly-(3)-hydroxybutyrate produced by Paraburkholderia xenovorans LB400 and its electrospun fibers.

Poly-3-hydroxybutyrate (PHB) is a biocompatible polymer produced by a wide variety of bacteria from different carbon sources. However, the carbon source effects on PHB properties are largely unknown. This study aimed to characterize PHB produced by Paraburkholderia xenovorans LB400 supplied with glucose (PHBg), mannitol (PHBm), or xylose (PHBx) as sole carbon sources and to evaluate their potential application as the main component of scaffolds obtained by electrospinning. The PHBs produced by strain LB400 had different molecular weights; the largest value corresponded to PHBm. The XRD-spectra revealed that PHB produced by strain LB400 from the three carbon sources are less crystalline than the commercially available polymer (PHBc). Moreover, the electrospinning process decreases even further their degree of crystallinity, which could lead to an improvement in the mechanical properties of the polymers. Relevantly, PHBx-microfibers exhibited mechanical characteristics similar to those of human skin. None of the scaffolds made of PHBs from strain LB400 grown in different carbon sources showed adverse effects on fibroblast cell growth. Thus, modifying the sugar used as the carbon source may be useful to tune the structural properties of PHB and its performance as a component of electrospun scaffolds, which may better fit specific biomedical applications.

Spanish version of the mini-BESTest: a translation, transcultural adaptation and validation study in patients with Parkinson's disease.

Balance is affected in numerous neurologic disorders, like stroke, multiple sclerosis and Parkinson's disease contributing to falls, and diminishing quality of life and functionality. The mini-BESTest is one of the most recommended scales to detect balance disorders in people with Parkinson's disease, which has solid psychometric properties. Unfortunately, this scale has not been validated in Chile and there are no other validated scales that can determine balance disorders in patients with Parkinson's disease to date. The study objective was to validate the mini-BESTest scale in Chilean Parkinson's disease patients. The translation and adaptation to Chilean Spanish of the mini-BESTest scale were made following a cross-cultural adaptation process, to then obtain face and content validity by an expert committee. Afterwards, the demographic data and psychometric properties of internal consistency and ceiling and floor effects were measured with a sample of 50 subjects with Parkinson's disease. Furthermore, 10 subjects of the sample were evaluated with the purpose of measuring inter rater reliability. The scale presented a good internal consistency (Cronbach's alpha = 0.845), and an excellent inter rater reliability (intraclass correlation coefficient = 0.97), no ceiling or floor effects were found. The results of the face and content validity and psychometric properties are adequate, achieving the validation of the mini-BESTest scale for balance in Chilean people with Parkinson's disease.

Polyhydroxyalkanoates as biomaterial for electrospun scaffolds.

Polyhydroxyalkanoates (PHA) are natural polyesters produced by microorganisms under carbon source excess and limiting nutrient conditions. However, these biopolymers possess low mechanical and thermal properties, decreasing their potential applications in the medical field. Electrospinning is a technique that forms fibers from different polymers. PHA electrospun fibers improve the mechanical properties and decrease the crystallinity of PHA, including poly-3-hydroxybutyrate and its copolymers, which is attributed to the metastable structure (ß-form) formation. Therefore, the mechanical properties of fibers are intrinsically related to their plane orientation. Aligned fibers present better mechanical properties than randomly oriented fibers. However, randomly oriented fibers promote cell-fiber interaction and cell infiltration. Fibers produced with PHA blended with other polymers have shown improved mechanical and biological properties. Gelatin, zein and cellulose acetate are the main natural polymers that have been blended with PHA for electrospun scaffolds. For scaffold production by coaxial electrospinning, gelatin has been used as a shell and PHA as the core. PHA have been combined with different synthetic polymers and plasticizers resulting in an increase in the PHA miscibility. Therefore, the use of electrospinning in the development of PHA-based scaffolds seems to be an attractive method to change the intrinsic polymer features, increasing and enhancing PHA applications in tissue engineering.

[Prefrontal activity and weekend alcoholism in the young]. / Actividad prefrontal y alcoholismo de fin de semana en jovenes.

BACKGROUND: High alcohol consumption by young people at weekends is a public health problem of considerable social and family importance. Chronic alcohol intake causes structural changes in the central nervous system, though the effects are not uniform throughout the brain. The prefrontal cortex (PC) has been reported to be one of the regions most sensitive to prolonged alcohol ingestion. OBJECTIVES: The effects of chronic ethanol exposure have been extensively studied. Our aim is to identify the neuropsychological deficits in PC function induced by intermittent heavy alcohol drinking in young adults. METHODS: Neuropsychological assessment was carried out on participants to examine their performance in PC-dependent tasks. 62 subjects (mean age 18.82+/-1.099) were assigned to one of three categories: 1) Those reporting heavy binge drinking of alcohol at weekends (ALE); 2) Those reporting moderate binge drinking of alcohol at weekends (ALM); and 3) Those reporting no alcohol intake (CTR). RESULTS AND CONCLUSIONS: The findings indicate that intermittent alcohol binge drinking, either heavy or moderate, in young people results in poorer performance in neuropsychological tasks such as Digits, Corsi or Stroop, which depend on correct PC functioning. Our results support the claim that the binge pattern of exposure to ethanol leads to neurocognitive and neurobehavioural impairment equivalent, in many respects, to that found in chronic drinkers. Moreover, intermittent heavy alcohol drinking in adolescence and early adulthood increases the risks of lifetime alcohol dependence and other psychopathologies.

Gallic acid loaded PEO-core/zein-shell nanofibers for chemopreventive action on gallbladder cancer cells.

Coaxial electrospinning was used to develop gallic acid (GA) loaded poly(ethylene oxide)/zein nanofibers in order to improve its chemopreventive action on human gallbladder cancer cells. Using a Plackett-Burman design, the effects of poly(ethylene oxide) and zein concentration and applied voltage on the diameter and morphology index of nanofibers were investigated. Coaxial nanofibers were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). GA loading efficiency as high as 77% was obtained under optimal process conditions. The coaxial nanofibers controlled GA release in acid and neutral pH medium. Cytotoxicity and reactive oxygen species (ROS) production on gallbladder cancer cell lines GB-d1 and NOZ in the presence of GA-nanofibers were assessed. GA-nanofibers triggered an increase in the cellular cytotoxicity compared with free GA on GB-d1 and NOZ cells. Statistically significant differences were found in ROS levels of GA-nanofibers compared with free GA on NOZ cells. Differently, ROS production on GB-d1 cell line was similar. Based on these results, the coaxial nanofibers obtained in this study under optimized operational conditions offer an alternative for the development of a GA release system with improved chemopreventive action on gallbladder cancer cells.

Synthesis, Biological Evaluation, and Molecular Simulation of Chalcones and Aurones as Selective MAO-B Inhibitors.

A series of chalcones and aurones were synthesized and evaluated in vitro as monoamine oxidase inhibitors (MAOi). Our results show that aurones, which had not been previously reported as MAOi, are MAO-B inhibitors. Thus, both families inhibited selectively the B isoform of MAO in the micromolar range, offering novel scaffolds for the design of new and potent MAO inhibitors. The main structural requirements for their activity were characterized with the aid of 3D-QSAR and docking studies.

Weekend alcoholism in youth and neurocognitive aging.

Numerous studies have shown that alcohol intake causes neuropsychological disorders that affect various brain structures. The «premature ageing¼ hypothesis proposes that the brain areas of alcoholics undergo deterioration similar to that observed in old age. We investigated whether alcohol abuse by young people (binge drinking) causes alterations comparable to some found in elderly people. Ninety-one people were divided into four groups: a) young people who abused alcohol; b) young people who drank alcohol in moderation; c) young people who did not drink alcohol; and d) elderly adults without any significant cognitive deterioration. All of them were assessed with a neuropsychological battery. We observed some similarities in the results obtained by young drinkers and the elderly participants, which would provide some support for the hypothesis of premature aging. The tasks that young drinkers performed worse were those related to executive functions, in which the prefrontal cortex plays an essential role. We also found differences between the two groups of young drinkers (moderate and high consumption), which leads us to believe that the amount of alcohol consumed and the pattern of consumption are factors to consider in relation to cognitive impairment.

Actividad prefrontal y alcoholismo de fin de semana en jóvenes / Prefrontal activity and weekend alcoholism in young

Antecedentes. El consumo elevado de alcohol por parte de jóvenes durante el fin de semana se está convirtiendo en un problema social y familiar importante pero también en un problema de salud considerable. El consumo abusivo ocasiona daños en el cerebro pero con diferente distribución, ya que la corteza prefrontal (CP) es una de las regiones que resulta más afectada. Objetivos. Hay numerosos estudios sobre los efectos del consumo crónico de alcohol. Nuestro objetivo es determinarlos déficits neuropsicológicos en la actividad prefrontal ocasionados por el consumo abusivo de alcohol de manera intermitente en adolescentes. Método. Se realizó una evaluación neuropsicológica a los sujetos para valorar su rendimiento en diversas tareas que implican a la CP. Participaron 62 sujetos (edad media 18.82±1.099) distribuidos en tres grupos: 1) Jóvenes que consumían alcohol de manera abusiva durante los fines de semana (ALE); 2) Jóvenes que consumían más moderadamente durante los fines de semana (ALM); y 3) Jóvenes que no consumían alcohol (CTR). Resultados y Conclusiones. Los resultados indican que el consumo abusivo intermitente de alcohol por parte de jóvenes, tanto de manera elevada como moderada, provoca un peor rendimiento en tareas neuropsicológicas como Dígitos, Corsi o Stroop, las cuales dependen de un correcto funcionamiento de la CP. Nuestros resultados apoyan la idea de que este patrón de consumo provoca un deterioro neurocognitivo y neuroconductual similar en muchos aspectos al observado en bebedores crónicos. Además, el consumo abusivo de fin de semana por parte de adolescentes y jóvenes incrementa el riesgo de desarrollar dependencia alcohólica y otras patologías en etapas posteriores de la vida

Background. High alcohol consumption by young people at weekends is a public health problem of considerable social and family importance. Chronic alcohol intake causes structural changes in the central nervous system, though the effects are not uniform throughout the brain. The prefrontal cortex (PC) has been reported to be one of the regions most sensitive to prolonged alcohol ingestion. Objectives. The effects of chronic ethanol exposure have been extensively studied. Our aim is to identify the neuropsychological deficits in PC function induced by intermittent heavy alcohol drinking in young adults. Methods. Neuropsychological assessment was carried out on participants to examine their performance in PC-dependent tasks. 62 subjects (mean age 18.82±1.099) were assigned toone of three categories: 1) Those reporting heavy binge drinking of alcohol at weekends (ALE); 2) Those reporting moderate binge drinking of alcohol at weekends (ALM); and 3) Those reporting no alcohol intake (CTR). Results and Conclusions. The findings indicate that intermittent alcohol binge dr inking, either heavy or moderate, in young people results in poorer performance in neuropsychological tasks such as Digits, Corsi or Stroop, which depend on correct PC functioning. Our results support the claim that the binge pattern of exposure to ethanol leads to neurocognitive and neurobehavioural impairment equivalent, in many respects, to that found inchronic drinkers. Moreover, intermittent heavy alcohol drinking in adolescence and early adulthood increases the risks of lifetime alcohol dependence and other psychopathologies