Safe and effective in vivo delivery of DNA and RNA using proteolipid vehicles.

Genetic medicines show promise for treating various diseases, yet clinical success has been limited by tolerability, scalability, and immunogenicity issues of current delivery platforms. To overcome these, we developed a proteolipid vehicle (PLV) by combining features from viral and non-viral approaches. PLVs incorporate fusion-associated small transmembrane (FAST) proteins isolated from fusogenic orthoreoviruses into a well-tolerated lipid formulation, using scalable microfluidic mixing. Screening a FAST protein library, we identified a chimeric FAST protein with enhanced membrane fusion activity that improved gene expression from an optimized lipid formulation. Systemically administered FAST-PLVs showed broad biodistribution and effective mRNA and DNA delivery in mouse and non-human primate models. FAST-PLVs show low immunogenicity and maintain activity upon repeat dosing. Systemic administration of follistatin DNA gene therapy with FAST-PLVs raised circulating follistatin levels and significantly increased muscle mass and grip strength. These results demonstrate the promising potential of FAST-PLVs for redosable gene therapies and genetic medicines.

Onco-Ontogeny of Squamous Cell Cancer of the First Pharyngeal Arch Derivatives.

Head and neck squamous cell carcinoma (H&NSCC) is an anatomic, biological, and genetic complex disease. It involves more than 1000 genes implied in its oncogenesis; for this review, we limit our search and description to the genes implied in the onco-ontogeny of the derivates from the first pharyngeal arch during embryo development. They can be grouped as transcription factors and signaling molecules (that act as growth factors that bind to receptors). Finally, we propose the term embryo-oncogenesis to refer to the activation, reactivation, and use of the genes involved in the embryo's development during the oncogenesis or malignant tumor invasion and metastasis events as part of an onco-ontogenic inverse process.

Design, Synthesis, and In Vitro and In Silico Evaluation of 1,3,4-Oxadiazoles as Anti-Trypanosoma cruzi and Anti-Leishmania mexicana Agents.

A series of novel 4-acetyl-1,3,4-oxadiazole derivatives was designed and synthesized for their biological evaluation in vitro against Trypanosoma cruzi and Leishmania mexicana. Additionally, compounds were evaluated by molecular docking on the cruzain of T. cruzi (TcCz) and the cysteine protease B (CPB) of L. mexicana (LmCPB) to know their potential mechanism of binding. Compound OX-12 had better trypanocidal activity against NINOA (IC50= 10.5 µM) and A1 (IC50= 21.7 µM) T. cruzi strains that reference drug benznidazole (IC50= 30.3 µM and 39.8 µM, respectively). Compound OX-2 had the best biological activity against L. mexicana in M379 (IC50= 11.9 µM) and FCQEPS (IC50= 34.0 µM) strains that the reference drug glucantime (IC50 ˃120 µM). All the compounds showed important interactions with residues on the active site of TcCz (Gly66, Trp26, Leu67, and Ala138) and LmCPB (Gly67, Asn62, Leu68, and Ala140). Finally, the molecular dynamics simulations of the compound OX-12 shown moderate stability from 40 to 115 ns with an RMSD value of 6.5 Å. Meanwhile, compound OX-2 showed a minor stability in complex with CPB from 25 to 200 ns of simulation (RMSD <9 Å). These results encourage to develop more potent and efficient trypanocidal and leishmanicidal agents using the 1,3,4-oxadiazole scaffold.

Bioinformatic and functional analysis of a PHB polymerase (PhbC) from Azospirillum baldaniorum.

BACKGROUND: Azospirillum baldaniorum Sp245 produces poly-ß-hydroxybutyrate, a biodegradable polymer with characteristics similar to synthetic thermoplastics, including polypropylene. In the synthesis pathway, the poly-ß-hydroxybutyrate synthase enzyme uses thioesters of 3-hydroxy butyryl-CoA as a substrate and catalyzes their polymerization with HS-CoA release. METHODS: A study was conducted using in silico analysis of the two phbC genes of A. baldaniorum Sp245. One was selected for amplification and cloning into the pEXP5- CT/TOPO® vector, which was analysed by restriction pattern, polymerase chain reaction, and sequencing. SDS-PAGE analysis determined the molecular weight of the PhbC1 protein from Azospirillum baldaniorum (AbPhbC1). The presence of the protein was confirmed by Western blotting using anti-polyhistidine monoclonal antibodies. The enzymatic activity in the crude extract of AbPhbC1 was determined by measuring the concentration of sulfhydryl groups using the Ellman method. A UV-Vis assay was performed. To confirm the presence of the poly-ß-hydroxybutyrate product, an NMR assay was performed. RESULTS: In silico analyses, it is revealed that AbPhbC1 and the PhbC2 protein from Azospirillum baldaniorum (AbPhbC2) retain the poly-ß-hydroxybutyrate polymerase and α/ß hydrolase domain. The Cys-His-Asp catalytic triad is highly conserved in all four polyß-hydroxyalkanoate synthases in the central subdomain, structurally similar to the reported crystallized proteins. The dimerization subdomain is different; in AbPhbC1, it is in the closed form; in AbPhbC2, it is in the open form; and in AbPhbC2, it lacks the EC region as class III and IV poly-ß-hydroxyalcanoate synthases. In vitro, the molecular weight of AbPhbC1 was 68 kDa. The polymerization of PHB by AbPhbC1 was detected by the release of HS-CoA from the quantification of SH. The UV-Vis scan showed a characteristic peak at 264 nm. A comparison of the NMR spectra of the bacterial and commercial poly-ß-hydroxybutyrate samples suggested their presence. CONCLUSION: In silico analyses suggested that AbPhbC1 and AbPhbC2 are structurally functional, except that AbPhbC2 might require the PhaR subunit for its activity; this strongly suggests that it could be a class IV poly-ß-hydroxyalcanoate synthase. UV-Vis scanning and NMR spectroscopy revealed the synthesis of poly-ß-hydroxybutyrate by the A. baldaniorum enzyme AbPhbC1, indicating that the enzyme is functional.

Human-centered design approach to building a transition readiness mHealth intervention for early adolescents.

OBJECTIVE: Mobile health (mHealth) interventions may be an efficacious strategy for promoting health behaviors among pediatric populations, but their success at the implementation stage has proven challenging. The purpose of this article is to provide a blueprint for using human-centered design (HCD) methods to maximize the potential for implementation, by sharing the example of a youth-, family-, and clinician-engaged process of creating an mHealth intervention aimed at promoting healthcare transition readiness. METHOD: Following HCD methods in partnership with three advisory councils, we conducted semistructured interviews with 13- to 15-year-old patients and their caregivers in two phases. In Phase 1, participants described challenges during the transition journey, and generated ideas regarding the format, content, and other qualities of the mHealth tool. For Phase 2, early adolescents and caregivers provided iterative feedback on two sequential intervention prototypes. Data were analyzed using thematic analysis in Phase 1 and the rapid assessment process for Phase 2. RESULTS: We interviewed 11 youth and 8 caregivers. The sample included adolescents with a range of chronic health conditions. In Phase 1, participants supported the idea of developing an autonomy-building tool, delivering transition readiness education via social media style videos. In Phase 2, participants responded positively to the successive prototypes and provided suggestions to make information accessible, relatable, and engaging. CONCLUSIONS: The procedures shared in this article could inform other researchers' plans to apply HCD in collaboration with implementation partners to develop mHealth interventions. Our future directions include iteratively developing more videos to promote transition readiness and implementing the intervention in clinical care.

Long Non-Coding RNAs and Alzheimer's Disease: Towards Personalized Diagnosis.

Alzheimer's disease (AD), a neurodegenerative disorder characterized by progressive cognitive decline, is the most common form of dementia. Currently, there is no single test that can diagnose AD, especially in understudied populations and developing countries. Instead, diagnosis is based on a combination of medical history, physical examination, cognitive testing, and brain imaging. Exosomes are extracellular nanovesicles, primarily composed of RNA, that participate in physiological processes related to AD pathogenesis such as cell proliferation, immune response, and neuronal and cardiovascular function. However, the identification and understanding of the potential role of long non-coding RNAs (lncRNAs) in AD diagnosis remain largely unexplored. Here, we clinically, cognitively, and genetically characterized a sample of 15 individuals diagnosed with AD (cases) and 15 controls from Barranquilla, Colombia. Advanced bioinformatics, analytics and Machine Learning (ML) techniques were used to identify lncRNAs differentially expressed between cases and controls. The expression of 28,909 lncRNAs was quantified. Of these, 18 were found to be differentially expressed and harbored in pivotal genes related to AD. Two lncRNAs, ENST00000608936 and ENST00000433747, show promise as diagnostic markers for AD, with ML models achieving > 95% sensitivity, specificity, and accuracy in both the training and testing datasets. These findings suggest that the expression profiles of lncRNAs could significantly contribute to advancing personalized AD diagnosis in this community, offering promising avenues for early detection and follow-up.

Solar Tracking Control Algorithm Based on Artificial Intelligence Applied to Large-Scale Bifacial Photovoltaic Power Plants.

The transition to a low-carbon economy is one of the main challenges of our time. In this context, solar energy, along with many other technologies, has been developed to optimize performance. For example, solar trackers follow the sun's path to increase the generation capacity of photovoltaic plants. However, several factors need consideration to further optimize this process. Important variables include the distance between panels, surface reflectivity, bifacial panels, and climate variations throughout the day. Thus, this paper proposes an artificial intelligence-based algorithm for solar trackers that takes all these factors into account-mainly weather variations and the distance between solar panels. The methodology can be replicated anywhere in the world, and its effectiveness has been validated in a real solar plant with bifacial panels located in northeastern Brazil. The algorithm achieved gains of up to 7.83% on a cloudy day and obtained an average energy gain of approximately 1.2% when compared to a commercial solar tracker algorithm.

A comparison of outcomes including bile duct injury of subtotal cholecystectomy versus open total cholecystectomy as bailout procedures for severe cholecystitis: A multicenter real-world study.

BACKGROUND: Dense inflammation obscuring the hepatocystic anatomy can hinder the ability to perform a safe standard laparoscopic cholecystectomy in severe cholecystitis, requiring use of a bailout procedure. We compared clinical outcomes of laparoscopic and open subtotal cholecystectomy against the traditional standard of open total cholecystectomy to identify the optimal bailout strategy for the difficult gallbladder. METHODS: A multicenter, multinational retrospective cohort study of patients who underwent bailout procedures for severe cholecystitis. Procedures were compared using one-way analysis of variance/Kruskal-Wallis tests and χ2 tests with multiple pairwise comparisons, maintaining a family-wise error rate at 0.05. Multiple multivariate linear/logistical regression models were created. RESULTS: In 11 centers, 727 bailout procedures were conducted: 317 laparoscopic subtotal cholecystectomies, 172 open subtotal cholecystectomies, and 238 open cholecystectomies. Baseline characteristics were similar among subgroups. Bile leak was common in laparoscopic and open fenestrating subtotal cholecystectomies, with increased intraoperative drain placements and postoperative endoscopic retrograde cholangiopancreatography(P < .05). In contrast, intraoperative bleeding (odds ratio = 3.71 [1.9, 7.22]), surgical site infection (odds ratio = 2.41 [1.09, 5.3]), intensive care unit admission (odds ratio = 2.65 [1.51, 4.63]), and length of stay (Δ = 2 days, P < .001) were higher in open procedures. Reoperation rates were higher for open reconstituting subtotal cholecystectomies (odds ratio = 3.43 [1.03, 11.44]) than other subtypes. The overall rate of bile duct injury was 1.1% and was not statistically different between groups. Laparoscopic subtotal cholecystectomy had a bile duct injury rate of 0.63%. CONCLUSION: Laparoscopic subtotal cholecystectomy is a feasible surgical bailout procedure in cases of severe cholecystitis where standard laparoscopic cholecystectomy may carry undue risk of bile duct injury. Open cholecystectomy remains a reasonable option.

Presence of SARS-CoV-2-specific T cells before vaccination in the Mexican population.

The immune response to SARS-CoV-2 has been extensively studied following the pandemic outbreak in 2020; however, the presence of specific T cells against SARS-CoV-2 before vaccination has not been evaluated in Mexico. In this study, we estimated the frequency of T CD4+ and T CD8+ cells that exhibit a specific response to S (spike) and N (nucleocapsid) proteins in a Mexican population. We collected 78 peripheral blood samples from unvaccinated subjects, and the presence of antibodies against spike (RBD) and N protein was determined. Peripheral blood mononuclear cells were isolated and stimulated with a pool of S or N protein peptides (Wuhan-Hu-1 strain). IL-1ß, IL-4, IL-6, IL-10, IL-2, IL-8, TNF-α, IFN-γ, and GM-CSF levels were quantified in the supernatant of the activated cells, and the cells were stained to assess the activation and memory phenotypes. Differential activation frequency dependent on serological status was observed in CD4+ cells but not in CD8+ cells. The predominantly activated population was the central memory T CD4+ cells. Only 10% of the population exhibited the same phenotype with respect to the response to nucleocapsid peptides. The cytokine profile differed between the S and N responses. S peptides induced a more proinflammatory response compared with the N peptides. In conclusion, in a Mexican cohort before vaccination, there was a significant response to the S and N SARS-CoV-2 proteins resulting from previous infections with seasonal coronaviruses or previous undetected exposure to SARS-CoV-2.

Medical students' knowledge about human papillomavirus (HPV), HPV vaccine and head and neck cancer.

The Human Papillomavirus (HPV) is a sexually transmitted infection that significantly affects the population worldwide. HPV preventive methods include vaccination, prophylactics, and education. Different types of cancers associated with HPV usually take years or decades to develop after infections, such as Head and Neck Cancer(HNC). Therefore, HPV prevention can be considered cancer prevention. A sample of medical students in Puerto Rico was evaluated to assess their knowledge about HPV, HPV vaccine, and HNC through two previously validated online questionnaires composed of 38 dichotomized questions, we measured HPV, HPV vaccination(HPVK), and HNC knowledge (HNCK). Out of 104 students surveyed, the mean HPVK score obtained was 20.07/26, SD = 3.86, while the mean score for HNCK was 6.37/12, SD = 1.78. Bidirectional stepwise regression showed study year and HPV Vaccine name had been the most influential variables on HPVK and HNCK. MS1 participants scored lower than MS2-MS4 participants, with no significant difference between MS2-MS4 scores. The results reveal knowledge gaps in HPV/HPV Vaccine and HNC among surveyed medical students. Our findings also suggest an association between knowledge of personal vaccination status, self-perceived risk, and how uncertainty in these factors may affect the medical students' understanding of HPV, HPV vaccination, and associated cancers.

Father's Absence in the Mongolian gerbil (Meriones unguiculatus) is associated with alterations in paternal behavior, T, cort, presence of ERα, and AR in mPOA/ BNST.

Testosterone (T), estrogen receptor alpha (ERα), and androgen receptor (AR) play a significant role in the regulation of paternal behavior. We determined the effects of deprivation of paternal care on alterations in paternal behavior, T concentrations in plasma, and the presence of ERα and AR in the medial preoptic area (mPOA), bed nucleus of the stria terminalis (BNST), medial amygdala (MeA), and olfactory bulb (OB), as well as the corticosterone (CORT) concentrations in plasma caused by deprivation of paternal care in the Mongolian gerbil (Meriones unguiculatus). Twenty pairs of gerbils were formed; the pups were deprived of paternal care (DPC) in 10 pairs. In another 10 pairs, the pups received paternal care (PC). Ten males raised in DPC condition and 10 males raised in PC conditions were mated with virgin females. When they became fathers, each DPC male and PC male was subjected to tests of paternal behavior on day three postpartum. Blood samples were obtained to quantify T and CORT concentrations, and the brains were removed for ERα and AR immunohistochemistry analyses. DPC males gave less care to their pups than PC males, and they had significantly lower T concentrations and levels of ERα and AR in the mPOA and BNST than PC males. DPC males also had higher CORT concentrations than PC males. These results suggest that in the Mongolian gerbil father's absence causes a decrease in paternal care in the offspring, which is associated with alterations in the neuroendocrine mechanisms that regulate it.

Computational Analysis of the Tripartite Interaction of Phasins (PhaP4 and 5)-Sigma Factor (σ24)-DNA of Azospirillum brasilense Sp7.

Azospirillum brasilense Sp7 produces PHB, which is covered by granule-associated proteins (GAPs). Phasins are the main GAPs. Previous studies have shown phasins can regulate PHB synthesis. When A. brasilense grows under stress conditions, it uses sigma factors to transcribe genes for survival. One of these factors is the σ24 factor. This study determined the possible interaction between phasins and the σ24 factor or phasin-σ24 factor complex and DNA. Three-dimensional structures of phasins and σ24 factor structures were predicted using the I-TASSER and SWISS-Model servers, respectively. Subsequently, a molecular docking between phasins and the σ24 factor was performed using the ClusPro 2.0 server, followed by molecular docking between protein complexes and DNA using the HDOCK server. Evaluation of the types of ligand-receptor interactions was performed using the BIOVIA Discovery Visualizer for three-dimensional diagrams, as well as the LigPlot server to obtain bi-dimensional diagrams. The results showed the phasins (Pha4Abs7 or Pha5Abs7)-σ24 factor complex was bound near the -35 box of the promoter region of the phaC gene. However, in the individual interaction of PhaP5Abs7 and the σ24 factor, with DNA, both proteins were bound to the -35 box. This did not occur with PhaP4Abs7, which was bound to the -10 box. This change could affect the transcription level of the phaC gene and possibly affect PHB synthesis.

Understanding and treating body image disturbances in eating disorders through body illusion interventions: a scoping review protocol.

BACKGROUND: We plan a scoping review aimed to synthesize what is known about the use of sensory-driven body illusion (BI) interventions for understanding and treating body image disturbance (BID) in people diagnosed with clinical eating disorders (EDs) and people with subclinical ED symptomatology. Our study will provide an outline of the current literature, identify gaps within the literature, and suggest novel directions for future research. METHODS/DESIGN: The scoping review process will be guided by the methodological framework of Arksey and O'Malley, subsequent recommendations by Levac et al., and the Preferred Reporting Items for Systematic Reviews and Meta-analysis Protocols Extension for Scoping Reviews guidelines. The following electronic databases will be systematically searched: MEDLINE (via PubMed), Web of Science, PsycINFO, and Scopus. Furthermore, to identify additional studies, we will use a search engine such as Google Scholar, and for grey literature, we will include Proquest for Dissertations and Theses. A search strategy has been identified and agreed upon by the research team in conjunction with a research librarian. Two researchers will screen the titles and abstracts independently and then assess the full text of the selected citations for the inclusion criteria. A third reviewer will be involved in cases of disagreement. Data will be extracted, collated, and charted to summarize all the relevant methods, outcomes, and key findings in the articles. DISCUSSION: A better understanding of this topic will aid in the development and refinement of current treatments aimed at treating BID in people with EDs. Implications and recommendations for research, policy, and practice in the context of the ED community will be discussed. SYSTEMATIC REVIEW REGISTRATION: https://osf.io/3bcm6/?view_only=83b2e8a2445d4266909992e3dfb51929.

Tuning the Potency of Farnesol-Modified Polyethylenimine with Polyanionic Trans-Booster to Enhance DNA Delivery.

Low molecular weight polyethylenimine (PEI) based lipopolymers become an attractive strategy to construct nonviral therapeutic carriers with promising transfection efficiency and minimal toxicity. Herein, this paper presents the design and synthesis of novel farnesol (Far) conjugated PEI, namely PEI1.2k-SA-Far7. The polymers had quick DNA complexation, effective DNA unpacking (dissociation), and cellular uptake abilities when complexed with plasmid DNA. However, they were unable to provide robust transfection in culture, indicating inability of Far grafting to improve the transfection efficacy significantly. To overcome this limitation, the commercially available polyanionic Trans-Booster additive, which is capable of displaying electrostatic interaction with PEI1.2k-SA-Far7, has been used to enhance the uptake of pDNA polyplexes and transgene expression. pDNA condensation was successfully achieved in the presence of the Trans-Booster with more stable polyplexes, and in vitro transfection efficacy of the polyplexes was improved to be comparable to that obtained with an established reference reagent. The PEI1.2k-SA-Far7/pDNA/Trans-Booster ternary complex exhibited good compatibility with cells and minimal hemolysis activity. This work demonstrates the exemplary potency of using additives in polyplexes and the potential of resultant ternary complexes for effective pDNA delivery.

Lipopolymer mediated siRNA delivery targeting aberrant oncogenes for effective therapy of myeloid leukemia in preclinical animal models.

The clinical development of tyrosine kinase inhibitors (TKI) has led to great strides in improving the survival of chronic myeloid leukemia (CML) and acute myeloid leukemia (AML) patients. But even the new generation TKIs are rendered futile in the face of evolving landscape of acquired mutations leading to drug resistance, necessitating the pursuit of alternative therapeutic approaches. In contrast to exploiting proteins as targets like most conventional drugs and TKIs, RNA Interference (RNAi) exerts its therapeutic action towards disease-driving aberrant genes. To realize the potential of RNAi, the major challenge is to efficiently deliver the therapeutic mediator of RNAi, small interfering RNA (siRNA) molecules. In this study, we explored the feasibility of using aliphatic lipid (linoleic acid and lauric acid)-grafted polymers (lipopolymers) for the delivery of siRNAs against the FLT3 oncogene in AML and BCR-ABL oncogene in CML. The lipopolymer delivered siRNA potently suppressed the proliferation AML and CML cells via silencing of the targeted oncogenes. In both AML and CML subcutaneous xenografts generated in NCG mice, intravenously administered lipopolymer/siRNA complexes displayed significant inhibitory effect on tumor growth. Combining siFLT3 complexes with gilteritinib allowed for reduction of effective drug dosage, longer duration of remission, and enhanced survival after relapse, compared to gilteritinib monotherapy. Anti-leukemic activity of siBCR-ABL complexes was similar in wild-type and TKI-resistant cells, and therapeutic efficacy was confirmed in vivo through prolonged survival of the NCG hosts systemically implanted with TKI-resistant cells. These results demonstrate the preclinical efficacy of lipopolymer facilitated siRNA delivery, providing a novel therapeutic platform for myeloid leukemias.

Estudio Histológico en Embriones de Cobayo (Cavia porcellus) y su Utilidad como Modelo para la Comprensión del Desarrollo Embrionario Humano / Histological Study in Guinea Pig Embryos (Cavia porcellus) and its Usefulness as a Model for Understanding Human Embryonic Development

El cobayo es un modelo animal ampliamente utilizado en la investigación biomédica debido a sus similitudes biológicas con los seres humanos. El objetivo de nuestro estudio es proporcionar sustento morfológico para utilizar preparados histológicos de embriones de cobayo como modelo de estudio para comprender los procesos del desarrollo embrionario humano. Nuestros resultados muestran que los embriones de cobayo presentan características morfológicas similares a las observadas en los embriones humanos, lo que sugiere que pueden utilizarse como un modelo efectivo para estudiar el desarrollo embrionario humano. Este hallazgo tiene importantes implicancias para la investigación y la docencia utilizando este modelo animal. Se analizaron preparados histológicos de embriones de cobayo teñidos con hematoxilina eosina, adquiridos por la Universidad Autónoma de Chile. Se tomaron microfotografías de preparados histológicos de cobayo en diferentes estadios del desarrollo y se seleccionaron las mejores imágenes para la descripción de estructuras y establecer estimados de la embriogénesis. Del análisis de los preparados se desprende que órganos como esófago, médula espinal y corazón presentan similitudes anatómicas e histológicas que hacen posible compararlas con el desarrollo embrionario humano y la edad de gestación en etapas tempranas. El uso de preparados de embriones de cobayo y su análisis desde un aspecto histológico resulta ser una estrategia metodológica factible debido a las similitudes en la embriogénesis de los mamíferos y las concordancias morfológicas con el desarrollo de los órganos entre humanos y roedores. Esto permite implementar este modelo animal como una herramienta para comprender el desarrollo embrionario humano.

SUMMARY: The guinea pig is an animal model widely used in biomedical research due to its biological similarities with humans. The objective of our study is to provide morphological support to use histological preparations of guinea pig embryos as a study model to understand the processes of human embryonic development. Our results show that guinea pig embryos present morphological characteristics similar to those observed in human embryos, suggesting that they can be used as an effective model to study human embryonic development. This finding has important implications for research and teaching using this animal model. Histological preparations of guinea pig embryos stained with hematoxylin eosin, acquired by the Autonomous University of Chile, were analyzed. Photomicrographs of histological preparations of guinea pigs at different stages of development were taken and the best images were selected to describe structures and establish estimates of embryogenesis. From the analysis of the preparations it is clear that organs such as the esophagus, spinal cord and heart present anatomical and histological similarities that make it possible to compare them with human embryonic development and gestation age in early stages. The use of guinea pig embryo preparations and their analysis from a histological aspect turns out to be a feasible methodological strategy due to the similarities in mammalian embryogenesis and the morphological concordances with the development of organs between humans and rodents. This allows this animal model to be implemented as a tool to understand human embryonic development.

Role of Incretins in Muscle Functionality, Metabolism, and Body Composition in Breast Cancer: A Metabolic Approach to Understanding This Pathology.

A poorly studied issue in women with breast cancer is the role of incretins (GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1)) in the quantity and quality of muscle mass in lean and obese individuals. The current report aims to analyze the patterns of association and the role of incretin in muscle functionality and body composition in women with cancer compared with healthy women (mammography BI-RADS I or II) to elucidate whether GIP and GLP-1 can be used to estimate the risk, in conjunction with overweight or obesity, for breast cancer. We designed a case-control study in women with a breast cancer diagnosis confirmed by biopsy in different clinical stages (CS; n = 87) and healthy women with a mastography BI-RADS I or II within the last year (n = 69). The women were grouped according to body mass index (BMI): lean (<25 kg/m2BS), overweight (≥25-<30 kg/m2BS), and obese (≥30 kg/m2BS). We found that GLP-1 and GIP levels over 18 pg/mL were associated with a risk of breast cancer (GIP OR = 36.5 and GLP-1 OR = 4.16, for the entire sample), particularly in obese women (GIP OR = 8.8 and GLP-1 OR = 6.5), and coincidentally with low muscle quality indexes, showed an association between obesity, cancer, incretin defects, and loss of muscle functionality.

Structure-based Virtual Screening from Natural Products as Inhibitors of SARS-CoV-2 Spike Protein and ACE2 Receptor Binding and their Biological Evaluation In vitro.

BACKGROUND: In the last years, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused more than 760 million infections and 6.9 million deaths. Currently, remains a public health problem with limited pharmacological treatments. Among the virus drug targets, the SARS-CoV-2 spike protein attracts the development of new anti-SARS-CoV-2 agents. OBJECTIVE: The aim of this work was to identify new compounds derived from natural products (BIOFACQUIM and Selleckchem databases) as potential inhibitors of the spike receptor binding domain (RBD)-ACE2 binding complex. METHODS: Molecular docking, molecular dynamics simulations, and ADME-Tox analysis were performed to screen and select the potential inhibitors. ELISA-based enzyme assay was done to confirm our predictive model. RESULTS: Twenty compounds were identified as potential binders of RBD of the spike protein. In vitro assay showed compound B-8 caused 48% inhibition at 50 µM, and their binding pattern exhibited interactions via hydrogen bonds with the key amino acid residues present on the RBD. CONCLUSION: Compound B-8 can be used as a scaffold to develop new and more efficient antiviral drugs.