Potential Use of Tomato Peel, a Rich Source of Lycopene, for Cancer Treatment.

Tomatoes are well known for their impressive nutritional value among vegetables. However, the industrial processing of tomatoes generates a significant amount of waste. Specifically, 10% to 18% of the raw materials used in tomato processing become waste. This waste can seriously affect ecosystems, such as freshwater bodies, wetlands, rivers, and other natural environments, if not properly managed. Interestingly, tomato waste, specifically the skin, contains lycopene, a potent antioxidant and antimutagenic that offers a range of health benefits. This makes it a valuable ingredient in industries such as food and cosmetics. In addition, researchers are exploring the potential of lycopene in the treatment of various types of cancer. This systematic review, guided by the PRISMA 2020 methodology, examined studies exploring the possibility of tomato peel as a source of lycopene and carotenoids for cancer treatment. The findings suggest that tomato peel extracts exhibit promising anticancer properties, underscoring the need for further investigation of possible therapeutic applications. The compiled literature reveals significant potential for using tomato peel to create new cancer treatments, which could potentially revolutionize the field of oncology. This underscores the importance of continued research and exploration, emphasizing the urgency and importance of the scientific community's contribution to this promising area of study.

Surfing Time-Motion Characteristics Possible to Gain Using Global Navigation Satellite Systems: A Systematic Review.

The popularity of surfing has increased exponentially, reaching its recent debut in the Olympic Games. However, surfing suffers from a relative immature technological market, while in other sports some technologies such as global navigation satellite systems (GNSSs) have become an essential work material for strength and conditioning and head coaches. This article aims to systematically review surfers' time-motion demands based on GNSSs. A systematic review of relevant articles was carried out using five main databases (PubMed, ProQuest Central, SCOPUS, SPORTDiscus, and FECYT (Web of Sciences, CCC, CIDW, KJD, MEDLINE, RSCI, and SCIELO)) until 23 March 2024. From the 238 studies initially found, 9 were included in the qualitative synthesis. In these, GNSS devices were employed with male (n = 143) and female (n = 28) surfers from different levels during competition and training situations. The studies show that the intermittent nature of the sport is evident, with substantial periods spent paddling and waiting punctuated by relatively brief high-intensity efforts when riding waves at high speeds. Notable differences emerged between competition and training demands, suggesting potential mismatches in how athletes currently prepare compared to event requirements. These novel insights allow quantifying surfing's harsh physiological requirements and could guide conditioning practices to better meet the sport's unique characteristics across populations. Therefore, training should emulate the lengthy aerobic capabilities needed for the paddling volumes observed, while also targeting the anaerobic systems to meet the repeated high-intensity surf riding efforts. However, inconsistencies in methods and reporting practices limit direct comparisons and comprehensive profiling of the sport's physical characteristics.

Integrative taxonomy reveals a new species of the glass knifefish genus Eigenmannia Jordan & Evermann, 1896 (Teleostei: Gymnotiformes: Sternopygidae) from the Rio Branco basin, Brazil.

A new species of Eigenmannia is described from the Rio Branco basin, Roraima, Brazil, based on morphological and molecular datasets. It is distinguished from all congeners by the following combination of characters: lateral line stripe extending from first perforated lateral line scale to distal portion of caudal filament, presence of superior midlateral stripe with origin posterior to end of body cavity anal-fin hyaline, caudal filament corresponding to 15.2%-43.1% LEA, subterminal mouth, ii,14-16 pectoral-fin rays, 166-219 anal-fin rays, 10-13 scale rows above lateral line at vertical through posterior tip of pectoral fin, 100-128 scales on lateral line, 22-28 premaxillary teeth, 19-23 dentary teeth, 7-10 endopterygoid teeth, depth of posterodorsal expansion on infraorbitals 1 + 2 half as long as infraorbitals 1 + 2 length, basibranchial 1 unossified, 13 precaudal vertebrae, and length of coronomeckelian bone corresponding to 20% of Meckel's cartilage length. The new species has significant genetic divergence from species with accessible DNA sequences in public repositories, ranging from 10.8% to 17.7%. An osteological description of the new species, a review of Eigenmannia cytochrome c oxidase subunit I (COI) sequences available in public repositories based on voucher examination, and a hypothesis of phylogenetic relationships for the new species based on COI are provided. The critical importance of including voucher examination as one of the steps in the pipeline for using DNA sequences present in public repositories in taxonomic and phylogenetic studies is discussed.

Electrospun scaffolds based on a PCL/starch blend reinforced with CaO nanoparticles for bone tissue engineering.

Electrospun nanocomposite scaffolds with improved bioactive and biological properties were fabricated from a blend of polycaprolactone (PCL) and starch, and then combined with 5 wt% of calcium oxide (CaO) nanoparticles sourced from eggshells. SEM analyses showed scaffolds with fibrillar morphology and a three-dimensional structure. The hydrophilicity of scaffolds was improved with starch and CaO nanoparticles, which was evidenced by enhanced water absorption (3500 %) for 7 days. In addition, PCL/Starch/CaO scaffolds exhibited major degradation, with a mass loss of approximately 60 % compared to PCL/Starch and PCL/CaO. The PCL/Starch/CaO scaffolds decreased in crystallinity as intermolecular interactions between the nanoparticles retarded the mobility of the polymeric chains, leading to a significant increase in Young's modulus (ca. 60 %) and a decrease in tensile strength and elongation at break, compared to neat PCL. SEM-EDS, FT-IR, and XRD analyses indicated that PCL/Starch/CaO scaffolds presented a higher biomineralization capacity due to the ability to form hydroxyapatite (HA) in their surface after 28 days. The PCL/Starch/CaO scaffolds showed attractive biological performance, allowing cell adhesion and viability of M3T3-E1 preosteoblastic cells. In vivo analysis using a subdermal dorsal model in Wistar rats showed superior biocompatibility and improved resorption process compared to a pure PCL matrix. This biological analysis suggested that the PCL/Starch/CaO electrospun mats are suitable scaffolds for guiding the regeneration of bone tissue.

Evolutionary and functional analyses of LRP5 in archaic and extant modern humans.

BACKGROUND: The human lineage has undergone a postcranial skeleton gracilization (i.e. lower bone mass and strength relative to body size) compared to other primates and archaic populations such as the Neanderthals. This gracilization has been traditionally explained by differences in the mechanical load that our ancestors exercised. However, there is growing evidence that gracilization could also be genetically influenced. RESULTS: We have analyzed the LRP5 gene, which is known to be associated with high bone mineral density conditions, from an evolutionary and functional point of view. Taking advantage of the published genomes of archaic Homo populations, our results suggest that this gene has a complex evolutionary history both between archaic and living humans and within living human populations. In particular, we identified the presence of different selective pressures in archaics and extant modern humans, as well as evidence of positive selection in the African and South East Asian populations from the 1000 Genomes Project. Furthermore, we observed a very limited evidence of archaic introgression in this gene (only at three haplotypes of East Asian ancestry out of the 1000 Genomes), compatible with a general erasing of the fingerprint of archaic introgression due to functional differences in archaics compared to extant modern humans. In agreement with this hypothesis, we observed private mutations in the archaic genomes that we experimentally validated as putatively increasing bone mineral density. In particular, four of five archaic missense mutations affecting the first ß-propeller of LRP5 displayed enhanced Wnt pathway activation, of which two also displayed reduced negative regulation. CONCLUSIONS: In summary, these data suggest a genetic component contributing to the understanding of skeletal differences between extant modern humans and archaic Homo populations.

Biological activity of lyophilized chitosan scaffolds with inclusion of chitosan and zinc oxide nanoparticles.

The constant demand for biocompatible and non-invasive materials for regenerative medicine in accidents and various diseases has driven the development of innovative biomaterials that promote biomedical applications. In this context, using sol-gel and ionotropic gelation methods, zinc oxide nanoparticles (NPs-ZnO) and chitosan nanoparticles (NPs-CS) were synthesized with sizes of 20.0 nm and 11.98 nm, respectively. These nanoparticles were incorporated into chitosan scaffolds through the freeze-drying method, generating a porous morphology with small (<100 µm), medium (100-200 µm), and large (200-450 µm) pore sizes. Moreover, the four formulations showed preliminary bioactivity after hydrolytic degradation, facilitating the formation of a hydroxyapatite (HA) layer on the scaffold surface, as evidenced by the presence of Ca (4%) and P (5.1%) during hydrolytic degradation. The scaffolds exhibited average antibacterial activity of F1 = 92.93%, F2 = 99.90%, F3 = 74.10%, and F4 = 88.72% against four bacterial strains: K. pneumoniae, E. cloacae, S. enterica, and S. aureus. In vivo, evaluation confirmed the biocompatibility of the functionalized scaffolds, where F2 showed accelerated resorption attributed to the NPs-ZnO. At the same time, F3 exhibited controlled degradation with NPs-CS acting as initiation points for degradation. On the other hand, F4 combined NPs-CS and NPs-ZnO, resulting in progressive degradation, reduced inflammation, and an organized extracellular matrix. All the results presented expand the boundaries in tissue engineering and regenerative medicine by highlighting the crucial role of nanoparticles in optimizing scaffold properties.

Prognostic Factors for Residual Lithiasis in Patients With Staghorn Calculi Undergoing Percutaneous Nephrolithotomy in the Maya Region of Yucatan, Mexico: A Case-Control Study.

BACKGROUND: Yucatan stands out as the state with the highest prevalence of urolithiasis in Mexico, placing significant demands on healthcare services, such as consultation and surgical intervention. Staghorn calculi are related to recurrent urinary tract infections, and their management is always surgical. The stone-free rate is a parameter used to measure the success of surgery, with residual stones considered those persisting four weeks after surgical management. There are understudied prognostic factors that can predict the success of achieving stone-free status, taking into account the number of stones, their location, and the anatomical variations of the patient's collecting system. The study aims to determine the prognostic factors for residual lithiasis in patients with staghorn calculi treated with percutaneous nephrolithotomy at the High Specialty Regional Hospital of the Yucatan Peninsula. METHODS: A case-control study was performed including 188 patients, aged 18 years or older, and diagnosed with staghorn calculus from January 2022 to June 2023, grouping the patients according to their stone-free rate evidence on postoperative computed tomography. Data were collected from the records of the Urology Department at a high-specialty hospital in Yucatan. The groups were analyzed, aiming to establish an association between preoperative factors and postoperative outcomes measured in terms of stone-free rate. RESULTS: A total of 188 patients with staghorn calculi were included, with a predominance in females (58.5%) and a mean age of 45.4 ± 11.9 years. The most common comorbidity was hypertension (29.8%), and 27.7% had a history of recurrent urinary tract infections. Regarding the Sampaio classification, B1 was the most prevalent in our population with 66 cases (35.1%), while Type A2 was the least common (13.8%). According to what was obtained through the multivariate logistic regression model, the calyceal anatomy Type A1 and A2 were associated with residual lithiasis (p= 0.016 OR: 2.994 CI: 1.223-7.331), and Grade IV was associated with a higher rate of residual lithiasis (p=0.005 CI: 1.586-13.100). A statistically significant association was found between stone burden and the presence of residual lithiasis (p=< 0.001). CONCLUSION: Guy's Score Grade IV showed a higher incidence of residual lithiasis, seemingly associated with stone burden, leading to the conclusion that both factors were categorized as predictors for the development of post-surgical residual lithiasis. Regarding anatomical variations according to Sampaio, it was observed that types A1 and A2 showed a lower rate of stone-free status. Therefore, we also consider them as variables that may influence the achievement of success in endourological management. Personalized patient assessment allows for more accurate prognostic factors, enabling a more comprehensive surgical planning in the presence of staghorn calculi.

The Expression Levels of TREX1 and IFN-α Are Associated with Immune Reconstitution in HIV-1-Infected Individuals.

TREX1 acts in the initial prevention of an autoimmune response, but it may contribute to the permissiveness of retrovirus infections. This study investigated the association between the levels of TREX1 gene expression with the polymorphisms TREX1 rs3135941 (T/C) and TREX1 rs3135945 (G/A), and the presence of antinuclear antibodies (ANA) in antiretroviral therapy (ART)-naïve individuals and after 1 year of treatment. Blood samples from 119 individuals with HIV-1 were subjected to genotyping of polymorphisms and quantification of TREX1 gene expression and HIV-1 viral load by qPCR. The concentration of IFN-α and the number of CD4+/CD8+ T lymphocytes were determined by ELISA and flow cytometry, respectively; ANA was investigated by immunofluorescence. A control group of 167 seronegative individuals was used for the comparison of genotypic frequencies. The frequency of the polymorphisms were not associated with HIV infection or with variations in the expression of TREX1 and IFN-α (p > 0.05). ART-naïve individuals exhibited higher TREX1 expression and lower IFN-α expression. After 1 year of ART, TREX1 levels were reduced, while IFN-α and CD4+ T lymphocytes were elevated (p < 0.05). Some individuals on ART presented ANA. These results suggest that ART-mediated restoration of immune competence is associated with a reduction in TREX1 expression, which may induce the development of ANA, regardless of the polymorphism investigated.

Microplastics suspended in dust from different indoor environments in Barranquilla, Colombia: Predominant microparticles?

Considering that microplastics (MPs) are classified as ubiquitous pollutants, that air quality affects human health, and that people remain indoors most of the time, the need has arisen to evaluate the exposure to MPs within the suspended dust in indoor environments. With this objective, the present study carried out passive sampling to analyze the precipitation of microparticles in some indoor residential environments (2 apartments) and workplaces (an office, a pastry shop, a gift shop, and a paint shop) in Barranquilla, Colombia. The quantification and physical characterization of microparticles were carried out under a stereomicroscope, and the chemical characterization was carried out by infrared microspectroscopy (µFTIR). The highest average concentration of MPs in the apartments was found in the air-conditioned rooms (1.1 × 104 MP/m2/day), and concerning the workplaces, the gift shop and the paint shop were the spaces with a higher proportion of MPs (6.0-6.1 × 103 MP/m2/day), with polyesters being the main synthetic polymers, but being semi-synthetic particles the predominant among the samples. Regarding its morphology, fibers were the most abundant shape (>90%), grouping mainly in the 1000-5000 µm range, while the few fragments found were mostly grouped below 50 µm. Exposure by inhalation of MPs in adults was estimated between 1.7 × 102-1.6 × 103 MP/kg/day, while by ingestion it ranged between 2.7 × 102-2.4 × 103 MPs/kg/day. On the other hand, within our research, a significant presence of non-plastic microparticles was found, which reached up to 69% in analyzed samples, corresponding mainly to cotton and cellulose, so we suggest that these should also be included in future studies that aim to estimate potential health implications from exposure to suspended micropollutants.

Regulatory T-cell frequency and function in acute myocardial infarction patients and its correlation with ventricular dysfunction.

A high percentage of patients with acute coronary syndrome develop heart failure due to the ischemic event. Regulatory T (Treg) cells are lymphocytes with suppressive capacity that control the immune response and include the conventional CD4+ CD25hi Foxp3+ cells and the CD4+ CD25var CD69+ LAP+ Foxp3- IL-10+ cells. No human follow-up studies focus on Treg cells' behavior after infarction and their possible relationship with ventricular function as a sign of postischemic cardiac remodeling. This study aimed to analyze, by flow cytometry, the circulating levels of CD69+ Treg cells and CD4+ CD25hi Foxp3+ cells, their IL-10+ production as well as their function in patients with acute myocardial infarction (AMI), and its possible relation with ventricular dysfunction. We found a significant difference in the percentage of CD4+ CD25hi Foxp3+ cells and IL-10+ MFI in patients with AMI at 72 hours compared with the healthy control group, and the levels of these cells were reduced 6 months post-AMI. Regarding the suppressive function of CD4+ CD25+ regulatory cells, they were dysfunctional at 3 and 6 months post-AMI. The frequency of CD69+ Treg cells was similar between patients with AMI at 72 hours postinfarction and the control groups. Moreover, the frequency of CD69+ Treg cells at 3 and 6 months postischemic event did not vary over time. Treg cells play a role in regulating inflammation after an AMI, and its function may be compromised in this pathology. This work is the first report to evaluate CD69+ Foxp3- Treg cells in AMI patients.

Prolonged, Atypical, and Fulminant Mpox in a HIV/HBV-Coinfected Patient: A Case Report.

Mpox (monkeypox) is a zoonotic disease that has been endemic in African countries for decades, with a recent global outbreak in countries around the world. A 39-year-old male with human immunodeficiency virus (HIV)-hepatitis B virus (HBV) coinfection and poor adherence to antiretroviral treatment, who was severely immunocompromised and had a concurrent diagnosis of Mpox, presented to our hospital with disseminated skin lesions (over 350 lesions), perianal ulcers, odynophagia, oral intolerance, diarrhea, and soft-tissue bacterial superinfection of the lower extremities. Laboratory results were consistent with HBV infection, with an absolute CD4 cell count of 40 cells/uL and a positive PCR result for monkeypox virus. An abdominopelvic CT scan showed evidence of severe proctitis and perineal soft-tissue infection. Sixty-five days after a positive monkeypox virus PCR, new lesions in the vesicular stage continued to appear, eventually developing hemodynamic instability and sepsis, resulting in a fatal outcome. Our case highlights the importance of intentionally looking for risk factors such as HIV/HBV coinfection and evaluating immune status (CD4 cell count) in patients with severe Mpox because it could be related to higher mortality.

Positive selection in gamete interaction proteins in Carnivora.

The absence of robust interspecific isolation barriers among pantherines, including the iconic South American jaguar (Panthera onca), led us to study molecular evolution of typically rapidly evolving reproductive proteins within this subfamily and related groups. In this study, we delved into the evolutionary forces acting on the zona pellucida (ZP) gamete interaction protein family and the sperm-oocyte fusion protein pair IZUMO1-JUNO across the Carnivora order, distinguishing between Caniformia and Feliformia suborders and anticipating few significant diversifying changes in the Pantherinae subfamily. A chromosome-resolved jaguar genome assembly facilitated coding sequences, enabling the reconstruction of protein evolutionary histories. Examining sequence variability across more than 30 Carnivora species revealed that Feliformia exhibited significantly lower diversity compared to its sister taxa, Caniformia. Molecular evolution analyses of ZP2 and ZP3, subunits directly involved in sperm-recognition, unveiled diversifying positive selection in Feliformia, Caniformia and Pantherinae, although no significant changes were linked to sperm binding. Structural cross-linking ZP subunits, ZP4 and ZP1 exhibited lower levels or complete absence of positive selection. Notably, the fusion protein IZUMO1 displayed prominent positive selection signatures and sites in basal lineages of both Caniformia and Feliformia, extending along the Caniformia subtree but absent in Pantherinae. Conversely, JUNO did not exhibit any positive selection signatures across tested lineages and clades. Eight Caniformia-specific positive selected sites in IZUMO1 were detected within two JUNO-interaction clusters. Our findings provide for the first time insights into the evolutionary trajectories of ZP proteins and the IZUMO1-JUNO gamete interaction pair within the Carnivora order.

Graphene Oxide (GO) for the Treatment of Bone Cancer: A Systematic Review and Bibliometric Analysis.

Cancer is a severe disease that, in 2022, caused more than 9.89 million deaths worldwide. One worrisome type of cancer is bone cancer, such as osteosarcoma and Ewing tumors, which occur more frequently in infants. This study shows an active interest in the use of graphene oxide and its derivatives in therapy against bone cancer. We present a systematic review analyzing the current state of the art related to the use of GO in treating osteosarcoma, through evaluating the existing literature. In this sense, studies focused on GO-based nanomaterials for potential applications against osteosarcoma were reviewed, which has revealed that there is an excellent trend toward the use of GO-based nanomaterials, based on their thermal and anti-cancer activities, for the treatment of osteosarcoma through various therapeutic approaches. However, more research is needed to develop highly efficient localized therapies. It is suggested, therefore, that photodynamic therapy, photothermal therapy, and the use of nanocarriers should be considered as non-invasive, more specific, and efficient alternatives in the treatment of osteosarcoma. These options present promising approaches to enhance the effectiveness of therapy while also seeking to reduce side effects and minimize the damage to surrounding healthy tissues. The bibliometric analysis of photothermal and photochemical treatments of graphene oxide and reduced graphene oxide from January 2004 to December 2022 extracted 948 documents with its search strategy, mainly related to research papers, review papers, and conference papers, demonstrating a high-impact field supported by the need for more selective and efficient bone cancer therapies. The central countries leading the research are the United States, Iran, Italy, Germany, China, South Korea, and Australia, with strong collaborations worldwide. At the same time, the most-cited papers were published in journals with impact factors of more than 6.0 (2021), with more than 290 citations. Additionally, the journals that published the most on the topic are high impact factor journals, according to the analysis performed, demonstrating the high impact of the research field.

Evaluation of the Antibacterial, Anti-Cervical Cancer Capacity, and Biocompatibility of Different Graphene Oxides.

Cancer stands as one of the deadliest diseases in human history, marked by an inferior prognosis. While traditional therapeutic methods like surgery, chemotherapy, and radiation have demonstrated success in inhibiting tumor cell growth, their side effects often limit overall benefits and patient acceptance. In this regard, three different graphene oxides (GO) with variations in their degrees of oxidation were studied chemically and tissue-wise. The accuracy of the synthesis of the different GO was verified by robust techniques using X-ray photoelectron spectroscopy (XPS), as well as conventional techniques such as infrared spectroscopy (FTIR), RAMAN spectroscopy, and X-ray diffraction (XRD). The presence of oxygenated groups was of great importance. It affected the physicochemical properties of each of the different graphene oxides demonstrated in the presence of new vibrational modes related to the formation of new bonds promoted by the graphitization of the materials. The toxicity analysis in the Hep-2 cell line of graphene oxide formulations at 250 µg/mL on the viability and proliferation of these tumor cells showed low activity. GO formulations did not show high antibacterial activity against Staphylococcus aureus and Escherichia coli strains. However, the different graphene oxides showed biocompatibility in the subdermal implantation model for 30, 60, and 90 days in the biomodels. This allowed healing by restoring hair and tissue architecture without triggering an aggressive immune response.

Litsea glaucescens Kuth possesses bactericidal activity against Listeria monocytogenes.

Background: Litsea glaucencens Kuth is an aromatic plant used for food seasoning food and in Mexican traditional medicine. Among, L. glaucencens leaves properties, it has proven antibacterial activity which can be used against opportunistic pathogens like Listeria monocytogenes, a foodborne bacteria that is the causal agent of listeriosis, a disease that can be fatal in susceptible individuals. The aim of this work was to investigate the antibacterial activity of L. glaucescens Kuth leaf extracts against L. monocytogenes and to identify its bioactive components. Material and Methods: L. glaucences leaves were macerated with four solvents of different polarity (n-hexane, dichloromethane, ethyl acetate, and methanol). To determine the capacity to inhibit bacterial proliferation in vitro, agar diffusion and microdilution methods were used. Next, we determined the minimal bactericidal concentration (MBC). Finally, we determined the ratio of MBC/MIC. Metabolites present in the active methanolic extract from L. glaucescens Kuth (LgMeOH) were purified by normal-phase open column chromatography. The structure of the antibacterial metabolite was determined using nuclear magnetic resonance (1H, 13C, COSY, HSQC) and by comparison with known compounds. Results: The LgMeOH extract was used to purify the compound responsible for the observed antimicrobial activity. This compound was identified as 5,7-dihydroxyflavanone (pinocembrin) by analysis of its spectroscopic data and comparison with those described. The MIC and MBC values obtained for pinocembrin were 0.68 mg/mL, and the ratio MBC/MIC for both LgMeOH and pinocembrin was one, which indicates bactericidal activity. Conclusion: L. glaucences Kuth leaves and its metabolite pinocembrin can be used to treat listeriosis due the bactericidal activity against L. monocytogenes.

Análisis de 27 marcadores STR del cromosoma Y en poblaciones de la selva del Perú / Analysis of 27 STR markers of the chromosome Y in the population of the jungle from Peru

Introducción: los marcadores de repeticiones cortas en tándem del cromosoma Y (Y-STR) se ubican en la región no recombinante del cromosoma Y, su herencia es por vía paterna, no son detectables en el ADN femenino. Estas propiedades hacen de los Y-STR una herramienta útil en las investigaciones forenses, como las agresiones sexuales, paternidades y otros delitos violentos; asimismo son útiles en estudios genealógicos y evolutivos. El objetivo de la investigación es ampliar la evidencia científica de la distribución por regiones o país de los haplotipos del cromosoma sexual Y, estudios similares en poblaciones peruanas son escasas debido al número menor de polimorfismos Y-STR de uso frecuente en genética forense y de poblaciones. Material y métodos: en la investigación se analizaron 141 muestras de ADN de la selva del Perú, de las que 104 muestras corresponden a la región de Iquitos (Loreto), 29 muestras son Awajun (Amazonas) y 8 muestras de Tambopata (Madre de Dios). Las muestras fueron procesadas empleando PCR directa con el kit Yfiler™ Plus PCR Amplification para 27 STR, los productos amplificados fueron analizados por electroforesis capilar en el Applied Biosystem™ 3500XL Genetic Analyzer y los datos obtenidos se importaron al software GeneMapper® ID-X v1.5 para generar los perfiles genéticos. Con los resultados obtenidos se realizó el análisis estadístico y la estructura poblacional. Resultados: de las 141 muestras se obtuvieron 106 haplotipos únicos. La diversidad genética para cada marcador Y-STR estuvo entre 0,317 y 0,919. La diversidad haplotípica para la muestra total fue de 0,9906. El estudio registra que los haplotipos Y-STR estudiados presentaron elevado polimorfismo en la población analizada y, por lo tanto, son de gran utilidad en estudios forenses de identificación humana, así como en genética de poblaciones cuando se investigan grupos o individuos de América Latina. (AU)

Y-chromosome-specific short tandem repeat (Y-STR) markers reside on the non-recombinant portion of the Y chromosome, their inheritance is paternal, they are not detectable in female DNA. These properties make Y-STRs a useful tool in forensic investigations such as sexual assault, parenting, and other violent crimes; likewise they are also useful in genealogical and evolutionary studies. The objective of the research is to expand the scientific evidence of the distribution by region or country of the Y sex chromosome haplotypes. Similar studies in Peruvian populations are scarce due to the smaller number of Y-STR polymorphisms frequently used in Forensic and Population Genetics. Material and method: In the investigation, 141 DNA samples from the jungle of Peru were analyzed, of which comprised of 104 samples from Iquitos region (Loreto), 29 samples from Awajun (Amazonas) and 8 samples from Tambopata (Madre de Dios). The samples were processed using direct PCR with the Yfiler™ Plus PCR Amplification kit for 27 STRs, the amplified products were analyzed by capillary electrophoresis on the Applied Biosystem™ 3500XL Genetic Analyzer, and the data obtained was imported into the GeneMapper® ID-X v1.5 software to generate the genetic profiles. With the results obtained, the statistical analysis and the population structure were carried out. Results: Of the 141 samples, 106 unique haplotypes were observed. Gene diversities for each Y-STR marker ranged from 0.317 to 0.919. The haplotype diversity for the total sample was 0.9906. This study supports that the Y-STR haplotypes in this population are highly polymorphic in the analyzed population and, therefore, are very useful in forensic studies of human identification, as well as in population genetics when investigating groups or individuals from Latin America. (AU)

From in-silico screening to in-vitro evaluation: Enhancing the detection of Microcystins with engineered PP1 mutant variants.

Cyanotoxins produced during harmful algal blooms (CyanoHABs) have become a worldwide issue of concern. Microcystins (MC) are the most ubiquitous group of cyanotoxins and have known carcinogenic and hepatotoxic effects. The protein phosphatase inhibition assays (PPIAs), based on the inhibition of Protein Phosphatase 1/2A (PP1/PP2A) by MC, are one of the most cost-effective options for detecting MC. In this work, we aimed to design in-silico and evaluate in-vitro mutant variants of the PP1 protein, in order to enhance their capabilities as a MC biosensor. To this end, we performed an in-silico active site-saturated mutagenesis screening, followed by stability and docking affinity calculation with the MCLR cyanotoxin. Candidates with improved both affinity and stability were further tested in a fully flexible active-site docking. The best-scored mutations (19) were individually analysed regarding their locations and interactions. Four of them (p.D197F; p.Q249Y; p.S129W; p.D220Q) were selected for in-vitro expression and evaluation. Mutant p.D197F, exhibited a significant increment in inhibition by MCLR with respect to the WT, while showing a non-significant difference in stability nor activity. This successful PP1 inhibition enhancement suggests the potential of the p.D197F variant for practical MC detection applications.

The Beta2-adrenergic agonist salbutamol synergizes with paclitaxel on cell proliferation and tumor growth in triple negative breast cancer models.

PURPOSE: Globally breast cancer accounts for 24.5% in incidence and 15.5% in cancer deaths in women. The triple-negative subtype lacks any specific therapy and is treated with chemotherapy, resulting in significant side-effects. We aimed to investigate if the dose of chemotherapeutic drugs could be diminished by co-administering it with the ß2-agonist salbutamol. METHODS: Cell proliferation was measured by thymidine incorporation; gene expression, by real-time PCR and protein phosphorylation by WB. Apoptosis was assessed by acridine orange / ethidium bromide and TUNEL tests. Public patient databases were consulted. Cells were inoculated to nude mice and their growth assessed. RESULTS: The ß2-agonist salbutamol synergizes in MDA-MB-231 cells in vitro with paclitaxel and doxorubicin on cell proliferation through ADRB2 receptors, while the ß-blocker propranolol does not. The expression of this receptor was assessed in patient databases and other cell lines. Triple negative samples had the lowest expression. Salbutamol and paclitaxel decreased MDA-MB-231 cell proliferation while their combination further inhibited it. The pathways involved were analyzed. When these cells were inoculated to nude mice, paclitaxel and salbutamol inhibited tumor growth. The combined effect was significantly greater. Paclitaxel increased the expression of MDR1 while salbutamol partially reversed this increase. CONCLUSION: While the effect of salbutamol was mainly on cell proliferation, suboptimal concentrations of paclitaxel provoked a very important enhancement of apoptosis. The latter enhanced transporter proteins as MDR1, whose expression were diminished by salbutamol. The expression of ADRB2 should be assessed in the biopsy or tumor to eventually select patients that could benefit from salbutamol repurposing.