Anti-ulcerogenic Potential of Kalanchoë gastonis-bonnieri Extracts in Male ICR Mice Model of Ethanol-induced Gastric Ulcers.

Peptic ulcers (PU) are a breach in the mucosa of the digestive tract and are related to several factors including an altered immune system and an unbalanced diet. Current treatment carries to long-term complications; therefore, the use of medicinal plants is an alternative for several inflammatory diseases including ulcerative lesions. Kalanchoë gastonis-bonnieri, is a succulent plant and, has been used in traditional medicine against gastric ulcers, inflammation, and cancer among others. The main goal of this work was to analyze the anti-ulcerogenic potential of extracts from leaves of K. gastonis-bonnieri in an assay of ethanol-induced gastric ulcers. An ethanolic extract was obtained by maceration from fresh leaves of K. gastonis-bonnieri, and fractions were obtained through bipartition and chemical fractioning. The chemical characterization of the extract was made through HPLC, GC-MS, and NMR. Total extract and fractions showed an anti-ulcerogenic effect in specimens of male ICR mice with a gastric ulcer index (UI) of 3.27-5.47. The recorded effect is attributed to the presence of terpenoid compounds such as ß-Amyrin acetate, which showed antioxidant properties and lessened formations of ulcers induced by ethanol administration in mice stomach.

Metabolic dysregulation of tricarboxylic acid cycle and oxidative phosphorylation in glioblastoma.

Glioblastoma multiforme (GBM) exhibits genetic alterations that induce the deregulation of oncogenic pathways, thus promoting metabolic adaptation. The modulation of metabolic enzyme activities is necessary to generate nucleotides, amino acids, and fatty acids, which provide energy and metabolic intermediates essential for fulfilling the biosynthetic needs of glioma cells. Moreover, the TCA cycle produces intermediates that play important roles in the metabolism of glucose, fatty acids, or non-essential amino acids, and act as signaling molecules associated with the activation of oncogenic pathways, transcriptional changes, and epigenetic modifications. In this review, we aim to explore how dysregulated metabolic enzymes from the TCA cycle and oxidative phosphorylation, along with their metabolites, modulate both catabolic and anabolic metabolic pathways, as well as pro-oncogenic signaling pathways, transcriptional changes, and epigenetic modifications in GBM cells, contributing to the formation, survival, growth, and invasion of glioma cells. Additionally, we discuss promising therapeutic strategies targeting key players in metabolic regulation. Therefore, understanding metabolic reprogramming is necessary to fully comprehend the biology of malignant gliomas and significantly improve patient survival.

Metabolic Roles of HIF1, c-Myc, and p53 in Glioma Cells.

The metabolic reprogramming that promotes tumorigenesis in glioblastoma is induced by dynamic alterations in the hypoxic tumor microenvironment, as well as in transcriptional and signaling networks, which result in changes in global genetic expression. The signaling pathways PI3K/AKT/mTOR and RAS/RAF/MEK/ERK stimulate cell metabolism, either directly or indirectly, by modulating the transcriptional factors p53, HIF1, and c-Myc. The overexpression of HIF1 and c-Myc, master regulators of cellular metabolism, is a key contributor to the synthesis of bioenergetic molecules that mediate glioma cell transformation, proliferation, survival, migration, and invasion by modifying the transcription levels of key gene groups involved in metabolism. Meanwhile, the tumor-suppressing protein p53, which negatively regulates HIF1 and c-Myc, is often lost in glioblastoma. Alterations in this triad of transcriptional factors induce a metabolic shift in glioma cells that allows them to adapt and survive changes such as mutations, hypoxia, acidosis, the presence of reactive oxygen species, and nutrient deprivation, by modulating the activity and expression of signaling molecules, enzymes, metabolites, transporters, and regulators involved in glycolysis and glutamine metabolism, the pentose phosphate cycle, the tricarboxylic acid cycle, and oxidative phosphorylation, as well as the synthesis and degradation of fatty acids and nucleic acids. This review summarizes our current knowledge on the role of HIF1, c-Myc, and p53 in the genic regulatory network for metabolism in glioma cells, as well as potential therapeutic inhibitors of these factors.

Effect of Trichomonacide 6-Nitro-1H-benzimidazole Derivative Compounds on Expression Level of Metabolic Genes in Trichomonas vaginalis.

The parasite Trichomonas vaginalis is the etiologic agent of trichomoniasis, the most common non-viral sexually transmitted disease worldwide. This infection often remains asymptomatic and is related to several health complications. The traditional treatment for trichomoniasis is the use of drugs of the 5-nitroimidazole family, such as metronidazole; however, scientific reports indicate an increasing number of drug-resistant strains. Benzimidazole derivatives could offer an alternative in the search for new anti-trichomonas drugs. In this sense, two attractive candidates are the compounds O2N-BZM7 and O2N-BZM9 (1H-benzimidazole derivatives), since, through in vitro tests, they have shown a higher trichomonacide activity. In this study, we determined the effect on the expression level of metabolic genes in T. vaginalis. The results show that genes involved in redox balance (NADHOX, G6PD::6PGL) are overexpressed, as well as the gene that participates in the first reaction of glycolysis (CK); on the other hand, structural genes such as ACT and TUB are decreased in expression in trophozoites treated with the compound O2N-BZM9, which would probably affect its morphology, motility and virulence. These results align with the trichomonacidal activity of the compounds, with benzimidazole O2N-BZM9 being the most potent, with an IC50 value of 4.8 µM. These results are promising for potential future therapeutic applications.

Effect of A Fluoride Toothpaste Containing Enzymes and Salivary Proteins on Periodontal Pathogens in Subjects with Black Stain: A Pilot Study.

OBJECTIVE: Black stain (BS) is an extrinsic dental discoloration particularly difficult to treat. Although its etiology is not fully clear yet, chromogenic bacteria inside the oral cavity seem to be involved. In this pilot study, we evaluated whether a toothpaste containing enzymes and salivary proteins could improve oral health and reduce the presence of periodontal pathogens in subjects predisposed to BS discoloration. MATERIALS AND METHODS: Twenty-six subjects were enrolled in the study: 10 subjects without BS; 16 subjects with BS, randomly assigned in two groups: test (n = 8) and control (n = 8). The test group used a toothpaste containing sodium fluoride, enzymes, and salivary proteins. The control group used a toothpaste with amine fluoride. At enrollment and after 14 weeks, participants were subjected to professional oral hygiene, evaluation of BS (through Shourie index) and oral health status, collection of saliva and dental plaque samples. The presence of periodontal pathogens in plaque and saliva of all subjects was investigated by molecular analysis (PCR). STATISTICAL ANALYSIS: The prevalence of investigated microbial species in patients with/without BS was performed by Chi-squared test. The variation in the prevalence of the investigated species after treatment in test and control group was analyzed by t-test. RESULTS: Clinical evaluation showed that 86% of participants with BS had a reduction in the Shourie index, independently from the toothpaste used. In particular, a greater reduction in the Shourie index was observed in subjects using an electric toothbrush. We did not observe an effect of the fluoride toothpaste containing enzymes and salivary proteins on the composition of the oral microbiota of the test subjects in comparison with controls. When comparing all subjects with BS (n = 16) and without BS (n = 10), P. gingivalis detection was significantly higher in saliva samples collected from subjects with BS (p = 0.0129). CONCLUSION: We verified that the use of an enzyme-containing toothpaste alone is not sufficient to prevent the formation of BS dental pigmentation in subjects predisposed to this discoloration. Mechanical cleaning, especially using electrical toothbrushes, seems to be useful to counteract BS formation. Moreover, our results suggest a possible association between BS and the presence of P. gingivalis at the salivary level.

Role of Glycolytic and Glutamine Metabolism Reprogramming on the Proliferation, Invasion, and Apoptosis Resistance through Modulation of Signaling Pathways in Glioblastoma.

Glioma cells exhibit genetic and metabolic alterations that affect the deregulation of several cellular signal transduction pathways, including those related to glucose metabolism. Moreover, oncogenic signaling pathways induce the expression of metabolic genes, increasing the metabolic enzyme activities and thus the critical biosynthetic pathways to generate nucleotides, amino acids, and fatty acids, which provide energy and metabolic intermediates that are essential to accomplish the biosynthetic needs of glioma cells. In this review, we aim to explore how dysregulated metabolic enzymes and their metabolites from primary metabolism pathways in glioblastoma (GBM) such as glycolysis and glutaminolysis modulate anabolic and catabolic metabolic pathways as well as pro-oncogenic signaling and contribute to the formation, survival, growth, and malignancy of glioma cells. Also, we discuss promising therapeutic strategies by targeting the key players in metabolic regulation. Therefore, the knowledge of metabolic reprogramming is necessary to fully understand the biology of malignant gliomas to improve patient survival significantly.

Comparação do protocolo de um hospital com a eficácia do TEGUM® na prevenção de radiodermites / Comparison of a hospital protocol with the effectiveness of TEGUM® in preventing radiodermatitis

Avaliar a eficácia do TEGUM® versus produto já utilizado na instituição na prevenção de radiodermites. Método: Estudo prospectivo, quantitativo, do tipo descritivo-exploratório em um hospital oncológico. O projeto foi aprovado pelo Comitê de Ética em Pesquisa com o CAAE: 24278319.8.0000.0099. Resultados: Dos 88 pacientes, 96,6% tinham câncer de mama. Em média os pacientes passaram por 25 aplicações de radioterapia, sendo 92% tratados em acelerador linear e 8% em cobalto. Dos 88 pacientes, tivemos 51,1% no Braço 1 (produto à base de Aloe Vera) e 48,9% no Braço 2 (Tegum®), e após levantamento a prevenção de radiodermite foi efetiva em 70,5% dos pacientes em ambos os braços. Conclusão: Concluímos que é necessária a prevenção, visando a redução das radiodermites nos pacientes submetidos a radioterapia. Além de mais estudos que possam definir melhor essa reação, melhorando a qualidade de vida durante e após o término do tratamento oncológico.(AU)

TTo evaluate the effectiveness of TEGUM® versus the product already used in the institution in preventing radiodermatitis. Method: Prospective, quantitative, descriptive-exploratory study in an oncology hospital. The project was approved by the Research Ethics Committee with CAAE: 24278319.8.0000.0099. Results: Of the 88 patients, 96.6% had breast cancer. On average, patients underwent 25 radiotherapy applications, with 92% treated with linear accelerator and 8% with cobalt. Of the 88 patients, we had 51.1% in Arm 1 (Aloe Vera-based product) and 48.9% in Arm 2 (Tegum®), and after survey the prevention of radiodermatitis was effective in 70.5% of patients in both arms. Conclusion: We conclude that prevention is necessary, aiming to reduce radiodermatitis in patients undergoing radiotherapy. In addition to more studies that can better define this reaction, improving quality of life during and after the end of cancer treatment.(AU)

Evaluar la efectividad de TEGUM® versus el producto ya utilizado en la institución para prevenir la radiodermatitis. Método: Estudio prospectivo, cuantitativo, descriptivo-exploratorio en un hospital de oncología. El proyecto fue aprobado por el Comité de Ética en Investigación con CAAE: 24278319.8.0000.0099. Resultados: De las 88 pacientes, el 96,6% presentó cáncer de mama. En promedio, los pacientes se sometieron a 25 aplicaciones de radioterapia, de las cuales el 92% fueron tratados con acelerador lineal y el 8% con cobalto. De los 88 pacientes, teníamos el 51,1 % en el grupo 1 (producto a base de aloe vera) y el 48,9 % en el grupo 2 (Tegum®), y después de la encuesta, la prevención de la radiodermatitis fue efectiva en el 70,5 % de los pacientes en ambos grupos. Conclusión: Concluimos que la prevención es necesaria, teniendo como objetivo reducir la radiodermatitis en pacientes sometidos a radioterapia. Además de más estudios que puedan definir mejor esta reacción, mejorando la calidad de vida durante y después de finalizar el tratamiento contra el cáncer.(AU)

An Overall View of the Functional and Structural Characterization of Glucose-6-Phosphate Dehydrogenase Variants in the Mexican Population.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency, affecting an estimated 500 million people worldwide, is a genetic disorder that causes human enzymopathies. Biochemical and genetic studies have identified several variants that produce different ranges of phenotypes; thus, depending on its severity, this enzymopathy is classified from the mildest (Class IV) to the most severe (Class I). Therefore, understanding the correlation between the mutation sites of G6PD and the resulting phenotype greatly enhances the current knowledge of enzymopathies' phenotypic and genotypic heterogeneity, which will assist both clinical diagnoses and personalized treatments for patients with G6PD deficiency. In this review, we analyzed and compared the structural and functional data from 21 characterized G6PD variants found in the Mexican population that we previously characterized. In order to contribute to the knowledge regarding the function and structure of the variants associated with G6PD deficiency, this review aimed to determine the molecular basis of G6PD and identify how these mutations could impact the structure, stability, and function of the enzyme and its relation with the clinical manifestations of this disease.

Cultivation of carbohydrate-rich microalgae with great settling properties using cooling tower wastewater.

Wastewater treatment and simultaneous production of value-added products with microalgae represent a sustainable alternative. Industrial wastewater, characterized by high C/N molar ratios, can naturally improve the carbohydrate content in microalgae without the need for any external source of carbon while degrading the organic matter, macro-nutrients, and micro-nutrients. This study aimed to understand the treatment, reuse, and valorization mechanisms of real cooling tower wastewater (CWW) from a cement-processing industry mixed with domestic wastewater (DW) to produce microalgal biomass with potential for synthesis of biofuels or other value-added products. For this purpose, three photobioreactors with different hydraulic retention times (HRT) were inoculated simultaneously using the CWW-DW mixture. Macro- and micro-nutrient consumption and accumulation, organic matter removal, algae growth, and carbohydrate content were monitored for 55 days. High COD (> 80%) and macronutrient removals (> 80% of N and P) were achieved in all the photoreactors, with heavy metals below the limits established by local standards. The best results showed maximum algal growth of 1.02 g SSV L-1 and 54% carbohydrate accumulation with a C/N ratio of 31.24 mol mol-1. Additionally, the harvested biomass presented a high Ca and Si content, ranging from 11 to 26% and 2 to 4%, respectively. Remarkably, big flocs were produced during microalgae growth, which enhanced natural settling for easy biomass harvesting. Overall, this process represents a sustainable alternative for CWW treatment and valorization, as well as a green tool for generating carbohydrate-rich biomass with the potential to produce biofuels and fertilizers.

Nitazoxanide Inhibits the Bifunctional Enzyme GlG6PD::6PGL of Giardia lamblia: Biochemical and In Silico Characterization of a New Druggable Target.

Giardiasis, which is caused by Giardia lamblia infection, is a relevant cause of morbidity and mortality worldwide. Because no vaccines are currently available to treat giardiasis, chemotherapeutic drugs are the main options for controlling infection. Evidence has shown that the nitro drug nitazoxanide (NTZ) is a commonly prescribed treatment for giardiasis; however, the mechanisms underlying NTZ's antigiardial activity are not well-understood. Herein, we identified the glucose-6-phosphate::6-phosphogluconate dehydrogenase (GlG6PD::6PGL) fused enzyme as a nitazoxanide target, as NTZ behaves as a GlG6PD::6PGL catalytic inhibitor. Furthermore, fluorescence assays suggest alterations in the stability of GlG6PD::6PGL protein, whereas the results indicate a loss of catalytic activity due to conformational and folding changes. Molecular docking and dynamic simulation studies suggest a model of NTZ binding on the active site of the G6PD domain and near the structural NADP+ binding site. The findings of this study provide a novel mechanistic basis and strategy for the antigiardial activity of the NTZ drug.

Laccase Production from Agrocybe pediades: Purification and Functional Characterization of a Consistent Laccase Isoenzyme in Liquid Culture.

Laccases are valuable enzymes as an excellent ecological alternative for bioremediation issues because they can oxidize persistent xenobiotic compounds. The production and characterization of extracellular laccases from saprotrophic fungi from disturbed environments have been scarcely explored, even though this could diversify their functional characteristics and expand the conditions in which they carry out their catalysis. Agrocybe pediades, isolated from a disturbed forest, produces an extracellular laccase in liquid culture. The enzyme was purified, identified and characterized. Copper and hexachlorobenzene do not function as inducers for the laccase produced. Partial amino acid sequences were obtained by LC-MS/MS that share similarity with laccases from other fungi. Purified laccase is a monomer with a molecular mass between 55-60 kDa and had an optimum activity at pH 5.0 and the optimum temperature at 45 °C using 2,6-dimethoxyphenol (2,6-DMP) as substrate. The Km and Vmax also determined with 2,6-DMP were 100 µM and 285 µmol∙min-1∙mg-1, respectively, showing that the laccase of A. pediades has a higher affinity for this substrate than that of other Agaricales. These features could provide a potential catalyst for different toxic substrates and in the future laccase could be used in environmental recovery processes.

Role of adjuvant therapy in intermediate-risk cervical cancer patients - Subanalyses of the SCCAN study.

OBJECTIVE: The "intermediate-risk" (IR) group of early-stage cervical cancer patients is characterized by negative pelvic lymph nodes and a combination of tumor-related prognostic risk factors such as tumor size ≥2 cm, lymphovascular space invasion (LVSI), and deep stromal invasion. However, the role of adjuvant treatment in these patients remains controversial. We investigated whether adjuvant (chemo)radiation is associated with a survival benefit after radical surgery in patients with IR cervical cancer. METHODS: We analyzed data from patients with IR cervical cancer (tumor size 2-4 cm plus LVSI OR tumor size >4 cm; N0; no parametrial invasion; clear surgical margins) who underwent primary curative-intent surgery between 2007 and 2016 and were retrospectively registered in the international multicenter Surveillance in Cervical CANcer (SCCAN) study. RESULTS: Of 692 analyzed patients, 274 (39.6%) received no adjuvant treatment (AT-) and 418 (60.4%) received radiotherapy or chemoradiotherapy (AT+). The 5-year disease-free survival (83.2% and 80.3%; PDFS = 0.365) and overall survival (88.7% and 89.0%; POS = 0.281) were not significantly different between the AT- and AT+ groups, respectively. Adjuvant (chemo)radiotherapy was not associated with a survival benefit after adjusting for confounding factors by case-control propensity score matching or in subgroup analyses of patients with tumor size ≥4 cm and <4 cm. In univariable analysis, adjuvant (chemo)radiotherapy was not identified as a prognostic factor in any of the subgroups (full cohort: PDFS = 0.365; POS = 0.282). CONCLUSION: Among patients with IR early-stage cervical cancer, radical surgery alone achieved equal disease-free and overall survival rates to those achieved by combining radical surgery with adjuvant (chemo)radiotherapy.

Tactile stimulation prevents disruptions in male rat copulatory behavior induced by artificial rearing.

Early life social interactions in gregarious mammals provide an important source of stimulation required for the development of species-typical behaviors. In the present study, complete deprivation of maternal and littermate contact through artificial rearing was used to examine the role of early social stimulation on copulatory behavior and the ejaculate in adult rats. We found that artificially reared naïve male rats were sexually motivated; nevertheless, they did not acquire the level of sexual experience that typically occurs during copulatory training. Disrupted expression of sexual experience of artificially reared rats was demonstrated by an inconsistent pattern of ejaculatory behavior across training tests. Artificial tactile stimulation applied during isolation prevented this disruption and rats achieved ejaculation in most copulatory tests. Despite the irregularity of ejaculatory behavior in isolated rats, their sperm count and seminal plug were similar to control maternally reared (sexually experienced) and artificially-reared rats that received tactile stimulation. These results suggest that tactile sensory information provided by the mother and/or littermates to the offspring is crucial for the development of copulatory behavior. The absence of social and/or tactile stimulation during early life compromises the ability of male rats to gain sexual experience in adulthood.

Pyridyl Methylsulfinyl Benzimidazole Derivatives as Promising Agents against Giardia lamblia and Trichomonas vaginalis.

Protozoan parasites, such as Giardia lamblia and Trichomonas vaginalis, cause the most prevalent infections in humans in developing countries and provoke significant morbidity and mortality in endemic countries. Despite its side-effects, metronidazole is still the drug of choice as a giardiacidal and trichomonacidal tissue-active agent. However, the emergence of metronidazole resistance and its evolved strategies of parasites to evade innate host defenses have hindered the identification and development of new therapeutic strategies against these parasites. Here, we tested five synthesized benzimidazole derivatives as possible drugs for treating giardiasis and trichomoniasis, probing the bifunctional enzyme glucose 6-phosphate dehydrogenase::6-phosphogluconolactone from G. lamblia (GlG6PD::6PGL) and T. vaginalis (TvG6PD::6PGL) as a drug target. The investigated benzimidazole derivatives were H-B2M1, H-B2M2, H2N-BZM6, O2N-BZM7, and O2N-BZM9. The recombinant enzymes were used in inhibition assays, and in silico computational predictions and spectroscopic studies were applied to follow the structural alteration of the enzymes and identify the possible mechanism of inhibition. We identified two potent benzimidazole compounds (O2N-BZM7 and O2N-BZM9), which are capable of inhibiting both protozoan G6PD::6PGL enzymes and in vitro assays with these parasites, showing that these compounds also affect their viability. These results demonstrate that other therapeutic targets of the compounds are the enzymes GlG6PD::6PGL and TvG6PD::6PGL, which contribute to their antiparasitic effect and their possible use in antigiardial and trichomonacidal therapies.

Identification of sugars as root exudates of the macrophyte species Juncus effusus and Philodendron cordatum in constructed wetland-microbial fuel cells during bioelectricity production.

Constructed wetland-microbial fuel cells (CW-MFCs) systems are a sustainable technology capable of producing bioelectricity and treating wastewater simultaneously. It is also possible to obtain bioelectricity from the photosynthetic substrates obtained by the rhizodeposition of macrophytes, where the electroactive microorganisms present in the rhizosphere use these compounds as biofuel. In the present study, the bioelectricity production capacity of Juncus effusus and Philodendron cordatum species was evaluated in a CW-MFC without an external carbon source. The Juncus effusus species showed a higher bioelectrochemical performance, as they recorded a maximum voltage of 399 mV, a power density of 63.7 mW/m2, a volumetric power density of 15.9 W/m3, an internal resistance of 200 Ω, an anodic potential of -368 mV, and a cathodic potential of 229 mV. In addition, different types of carbohydrates in the form of sugars (sucrose, fructose, galactose, and glucose) were quantified by liquid chromatography, with concentrations of 100-450 µg/L. Chromatographic analysis were performed from the root exudates released in the effluent of both species of macrophyte. Sucrose and glucose were the types of sugars that produced the largest amount with portions of up to 35% and 24%, respectively. Sugars are compounds that worked as electron donors for the production of bioelectricity by using endogenous substrates that fed the anodic biofilm. Consumption was 45-55% for sucrose and 40-65% for glucose. Of the different macrophytes evaluated in the CW-MFCs, it was observed that the production of bioelectricity differs mainly due to the quantity of the root exudates released in the rhizosphere.

Biochemical and Kinetic Characterization of the Glucose-6-Phosphate Dehydrogenase from Helicobacter pylori Strain 29CaP.

Helicobacter pylori (H. pylori) has been proposed as the foremost risk factor for the development of gastric cancer. We found that H. pylori express the enzyme glucose-6-phosphate dehydrogenase (HpG6PD), which participates in glucose metabolism via the pentose phosphate pathway. Thus, we hypothesized that if the biochemical and physicochemical characteristics of HpG6PD contrast with the host G6PD (human G6PD, HsG6PD), HpG6PD becomes a potential target for novel drugs against H. pylori. In this work, we characterized the biochemical properties of the HpG6PD from the H.pylori strain 29CaP and expressed the active recombinant protein, to analyze its steady-state kinetics, thermostability, and biophysical aspects. In addition, we analyzed the HpG6PD in silico structural properties to compare them with those of the HsG6PD. The optimal pH for enzyme activity was 7.5, with a T1/2 of 46.6 °C, at an optimum stability temperature of 37 °C. The apparent Km values calculated for G6P and NADP+ were 75.0 and 12.8 µM, respectively. G6P does not protect HpG6PD from trypsin digestion, but NADP+ does protect the enzyme from trypsin and guanidine hydrochloride (Gdn-HCl). The biochemical characterization of HpG6PD contributes to knowledge regarding H. pylori metabolism and opens up the possibility of using this enzyme as a potential target for specific and efficient treatment against this pathogen; structural alignment indicates that the three-dimensional (3D) homodimer model of the G6PD protein from H. pylori is different from the 3D G6PD of Homo sapiens.

Sources, Characteristics, and Therapeutic Applications of Mesenchymal Cells in Tissue Engineering.

Tissue engineering (TE) is a therapeutic option within regenerative medicine that allows to mimic the original cell environment and functional organization of the cell types necessary for the recovery or regeneration of damaged tissue using cell sources, scaffolds, and bioreactors. Among the cell sources, the utilization of mesenchymal cells (MSCs) has gained great interest because these multipotent cells are capable of differentiating into diverse tissues, in addition to their self-renewal capacity to maintain their cell population, thus representing a therapeutic alternative for those diseases that can only be controlled with palliative treatments. This review aimed to summarize the state of the art of the main sources of MSCs as well as particular characteristics of each subtype and applications of MSCs in TE in seven different areas (neural, osseous, epithelial, cartilage, osteochondral, muscle, and cardiac) with a systemic revision of advances made in the last 10 years. It was observed that bone marrow-derived MSCs are the principal type of MSCs used in TE, and the most commonly employed techniques for MSCs characterization are immunodetection techniques. Moreover, the utilization of natural biomaterials is higher (41.96%) than that of synthetic biomaterials (18.75%) for the construction of the scaffolds in which cells are seeded. Further, this review shows alternatives of MSCs derived from other tissues and diverse strategies that can improve this area of regenerative medicine.

Effects of feeds, supplemented with humic substances and calcium carbonate, on performance, egg quality and heart rate variability in laying hens.

This study aimed to determine the effects of in-feed inclusion of humic substances (HS) and/or calcium carbonate (CaCO3) on the performance and welfare of laying hens. A total number of 144 Hy-Line Brown laying hens (55 weeks old) were randomly assigned to four treatments, T1-T4 (36 birds per treatment). T1 hens were fed on a control diet without HS or CaCO3, T2 hens were fed on the control diet + 2.00 g per bird per day CaCO3, T3 hens were fed on the control diet + 0.20% HS and T4 hens were fed on the control diet + 0.20% HS + 2.00 g/bird/day CaCO3. The experiment started after 15 days of adaptation and lasted 8 weeks. The parameters evaluated were percentage of hen-day egg production, food consumption, mortality, egg quality parameters and heart rate variability (welfare indicator). Hens in the T3 group showed a significantly lower feed intake than those in the other three groups, however, significantly higher daily egg production was recorded in groups T3 and T4 compared to T1 and T2. Eggshell quality characteristics were significantly improved by HS supplementation and eggs laid by hens in groups T1, and T4 presented paler yolk and shell color than those in the other groups. In conclusion, these results indicated that in-feed inclusion of HS had a beneficial effect on laying hens' productive performance including egg production and eggshells quality.

Threshold for copulation-induced analgesia varies according to the ejaculatory endophenotypes in rats.

Analgesia may be modulated by multiple internal and external factors. In prior studies, copulatory-induced analgesia was demonstrated using the vocalization threshold to tail shock (VTTS) in male and female rats. Three ejaculatory endophenotypes have been characterized in male Wistar rats based upon their ejaculation latency (EL). Since intromissions and ejaculations produce analgesia, and these copulatory patterns are performed with different frequency depending on the male's ejaculatory endophenotype, we hypothesized that copulation-induced analgesia would vary in relation to these endophenotypes. In the present study, we used three groups according to the EL (medians): rapid ejaculators (236 s; n = 21), intermediate ejaculators (663.2 s; n = 20) and sluggish ejaculators (1582.2 s; n = 8). Our aim was to evaluate whether copulation-induced analgesia is related to the ejaculatory endophenotypes during two consecutive ejaculatory series (EJS). In the first EJS, the VTTS of the rapid ejaculators was significantly higher than that of intermediate and sluggish rats. At the onset of the second EJS, the VTTS of the rapid and intermediate ejaculators was significantly higher than that of the sluggish rats. No differences in VTTS were observed during the first or second post-ejaculatory intervals among the three groups. These findings provide evidence that the more intromissions that occurred per unit time, the higher was the level of analgesia.

[Capacity of the oleaginous yeast Clavispora lusitaniae Hi2 to transform agroindustrial residues into lipids]. / Potencial de la levadura oleaginosa Clavispora lusitaniae Hi2 en la conversión de residuos agroindustriales a lípidos.

BACKGROUND: Single-cell oils obtained from oleaginous microorganisms by using lignocellulosic waste hydrolysates are an alternative for producing biodiesel. AIMS: To isolate a yeast strain able to produce lipids from centrifuged nejayote (CN), hydrolyzed nejayote solids (HNS) and hydrolyzed sugarcane bagasse (HSB). METHODS: In order to identify the yeasts recovered, 26S ribosomal DNA was sequenced. The metabolic profile was assessed by using API20C AUX strips. The nutritional characterization of CN, HNS and HSB was performed by quantifying reducing sugars, total carbohydrates, starch, protein and total nitrogen. The biomass and lipid production ability were evaluated by performing growth kinetics of Clavispora lusitaniae Hi2 in combined culture media. RESULTS: Six oleaginous yeast strains were isolated and identified, selecting C. lusitaniae Hi2 to study its lipids production by using nejayote. The C. lusitaniae Hi2 strain can use glucose, xylose, arabinose, galactose and cellobiose as carbon sources. Cultures of C. lusitaniae Hi2 presented the best biomass (5.6±0.28 g/L) and lipid production (0.99±0.09 g/L) at 20 h of incubation with the CN:HNS media in the 25:75 and 50:50 ratios, respectively. CONCLUSIONS: The use of CN, HNS and HSB for the growth of C. lusitaniae Hi2 is an option to take advantage of these agro-industrial residues and generate compounds of biotechnological interest.