Emblica officinalis Gaertn as a Potential Alternative Therapy for the Treatment of Epilepsy: An Animal Study.

Introduction: Epilepsy is a neurological disorder characterized by recurrent seizures. Although antiepileptic drugs (AEDs) reduce the frequency of epileptic seizures, they can cause renal and hepatic damage. Several preclinical studies have indicated that Emblica officinalis Gaertn (AMLA) exerts an anticonvulsant effect related to its tannin and polyphenol content. Objective: We aim to evaluate the anticonvulsant effects of chronic oral AMLA administration and its impact on biochemical and hematological parameters in rats. Methods: Twenty-eight male Wistar rats (250 to 300 g) were divided into four experimental groups (n = 7): vehicle (purified water), AMLA (500 and 700 mg/kg), and carbamazepine (CBZ) (300 mg/kg) as the pharmacological control of anticonvulsant activity. Treatments were administered orally every 24 hours for 28 days, while carbamazepine was administered every 48 hours for 5 days before the behavioral, biochemical, and hematological test. On day 29, Status epilepticus (SE) was induced using the lithium-pilocarpine model (3 mEq/kg, i.p. and 30 mg/kg, s.c.), after which the behavioral and biochemical effects were evaluated. Results: The AMLA 500 mg/kg and CBZ 300 mg/kg groups presented fewer phase V seizures than the vehicle group did. None of the treatments modified biochemical or hematological parameters. Conclusion: AMLA could be considered as a potential alternative therapy for the treatment of epilepsy.

Novel human recombinant N-acetylgalactosamine-6-sulfate sulfatase produced in a glyco-engineered Escherichia coli strain.

Mucopolysaccharidosis IVA (MPS IVA) is a lysosomal storage disease caused by mutations in the gene encoding the lysosomal enzyme N-acetylgalactosamine-6-sulfate sulfatase (GALNS), resulting in the accumulation of keratan sulfate (KS) and chondroitin-6-sulfate (C6S). Previously, it was reported the production of an active human recombinant GALNS (rGALNS) in E. coli BL21(DE3). However, this recombinant enzyme was not taken up by HEK293 cells or MPS IVA skin fibroblasts. Here, we leveraged a glyco-engineered E. coli strain to produce a recombinant human GALNS bearing the eukaryotic trimannosyl core N-glycan, Man3GlcNAc2 (rGALNSoptGly). The N-glycosylated GALNS was produced at 100 mL and 1.65 L scales, purified and characterized with respect to pH stability, enzyme kinetic parameters, cell uptake, and KS clearance. The results showed that the addition of trimannosyl core N-glycans enhanced both protein stability and substrate affinity. rGALNSoptGly was capture through a mannose receptor-mediated process. This enzyme was delivered to the lysosome, where it reduced KS storage in human MPS IVA fibroblasts. This study demonstrates the potential of a glyco-engineered E. coli for producing a fully functional GALNS enzyme. It may offer an economic approach for the biosynthesis of a therapeutic glycoprotein that could prove useful for MPS IVA treatment. This strategy could be extended to other lysosomal enzymes that rely on the presence of mannose N-glycans for cell uptake.

Enhancing antioxidant properties of CeO2 nanoparticles with Nd3+ doping: structural, biological, and machine learning insights.

The antioxidant capabilities of nanoparticles are contingent upon various factors, including their shape, size, and chemical composition. Herein, novel Nd-doped CeO2 nanoparticles were synthesized and the neodymium content was varied to investigate the synergistic impact on the antioxidant properties of CeO2 nanoparticles. Incorporating Nd3+ induced changes in lattice parameters and significantly altered the morphology from nanoparticles to nanorods. The biological activity of Nd-doped CeO2 was examined against pathogenic bacterial strains, breast cancer cell lines, and antioxidant models. The antibacterial and anticancer activities of nanoparticles were not observed, which could be associated with the Ce3+/Ce4+ ratio. Notably, the incorporation of neodymium improved the antioxidant capacity of CeO2. Machine learning techniques were employed to forecast the antioxidant activity to enhance understanding and predictive capabilities. Among these models, the random forest model exhibited the highest accuracy at 96.35%, establishing it as a robust computational tool for elucidating the biological behavior of Nd-doped CeO2 nanoparticles. This study presents the first exploration of the influence of Nd3+ on the structural, optical, and biological attributes of CeO2, contributing valuable insights and extending the application of machine learning in predicting the therapeutic efficacy of inorganic nanomaterials.

Lanthanide-Doped ZnO Nanoparticles: Unraveling Their Role in Cytotoxicity, Antioxidant Capacity, and Nanotoxicology.

This study used a sonochemical synthesis method to prepare (La, Sm)-doped ZnO nanoparticles (NPs). The effect of incorporating these lanthanide elements on the structural, optical, and morphological properties of ZnO-NPs was analyzed. The cytotoxicity and the reactive oxygen species (ROS) generation capacity of ZnO-NPs were evaluated against breast (MCF7) and colon (HT29) cancer cell lines. Their antioxidant activity was analyzed using a DPPH assay, and their toxicity towards Artemia salina nauplii was also evaluated. The results revealed that treatment with NPs resulted in the death of 10.559-42.546% and 18.230-38.643% of MCF7 and HT29 cells, respectively. This effect was attributed to the ability of NPs to downregulate ROS formation within the two cell lines in a dose-dependent manner. In the DPPH assay, treatment with (La, Sm)-doped ZnO-NPs inhibited the generation of free radicals at IC50 values ranging from 3.898 to 126.948 µg/mL. Against A. salina nauplii, the synthesized NPs did not cause death nor induce morphological changes at the tested concentrations. A series of machine learning (ML) models were used to predict the biological performance of (La, Sm)-doped ZnO-NPs. Among the designed ML models, the gradient boosting model resulted in the greatest mean absolute error (MAE) (MAE 9.027, R2 = 0.86). The data generated in this work provide innovative insights into the influence of La and Sm on the structural arrangement and chemical features of ZnO-NPs, together with their cytotoxicity, antioxidant activity, and in vivo toxicity.

Factores psicosocioculturales relacionados con la formación técnica o profesional del personal de enfermería en Tlaxcala, México / Psychosociocultural factors related to the technical or professional training of nursing staff in Tlaxcala, México

Introducción: las demandas actuales en el cuidado de los pacientes ameritan cambios curriculares en la formación del personal de enfermería y su relación con los factores socioculturales. Objetivo: identificar y describir los factores psico-socioculturales que se relacionan con la formación técnica o profesional del personal de enfermería en Tlaxcala. Metodología: se realizó un estudio transversal descriptivo en el Hospital General de Zona No. 1, con personal de enfermería en cursos de formación técnico o profesional, seleccionados de manera no probabilística. Variables: edad, sexo, factores psico-socioculturales. Análisis con frecuencias, porcentajes y medidas de dispersión. Resultados: de un total de 51 enfermeras, la edad promedio es de 46.4 ± 8.9 años y 44% son enfermeras generales. Los factores referidos por el personal son: nivel de preparatoria (98%), nivel técnico (46%), estudios de licenciatura (84%), problemas económicos (48%), apoyo familiar (82%), enfermedad (8%), trabajo y estudio (20%), cambio de residencia (10%), interés (94%), vocación (100%), escuela de procedencia (94%), rendimiento escolar (8%), programa académico (88%), forma de trabajo (10%), técnicas docentes (10%), carga académica (14%), ambiente académico (84%), reglamento escolar (2%) y prácticas (4%). Conclusiones: el género se relaciona con la formación de nivel licenciatura y la edad con el nivel técnico, nivel licenciatura, trabajo y estudio, y carga académica; el estado civil con el interés por estudiar; y la religión con el apoyo docente.

Abstract Introduction: Current demands in patient care warrant curricular changes in the training of nursing personnel and their relationship with sociocultural factors. Objective: Identify and describe the Psychosocial Cultural factors that are related to the technical or professional training of nursing staff in Tlaxcala. Methodology: A descriptive cross-sectional study was carried out at the General Hospital of Zone No. 1, with nursing staff in technical or professional training courses, selected in a non-probabilistic manner. Variables: age, sex, Psychosociocultural factors. Analysis with frequencies, percentages and dispersion measures. Results: Of a total of 51 nurses, the average age is 46.4 ± 8.9 years and 44% are general nurses. The factors referred to by the staff are: high school level (98%), technical level (46%), bachelor's studies (84%), economic problems (48%), family support (82%), illness (8%), work and study (20%), change of residence (10%), interest (94%), vocation (100%), school of origin (94%), school performance (8%), academic program (88%), form of work (10%), teaching techniques (10%), academic load (14%), academic environment (84%), school regulations (2%) and practices (4%). Conclusions: Gender is related to bachelor's level training and age to technical level, bachelor's level, work and study, and academic load; marital status with interest in studying; and religion with teaching support.

Pre-differentiation GenX exposure induced neurotoxicity in human dopaminergic-like neurons.

GenX, also known as hexafluoropropylene oxide dimer acid (HFPO-DA) was introduced as a safer alternative to perfluorooctanoic acid (PFOA) in 2009. After nearly two decades of applications there are increasing safety concerns about GenX due to its association with various organ damages. Few studies, however, have systematically assessed the molecular neurotoxicity of low-dose GenX exposure. Here, we evaluated the effects of pre-differentiation exposure of GenX on dopaminergic (DA) -like neurons using SH-SY5Y cell line; and assessed changes in epigenome, mitochondrion, and neuronal characteristics. Low dose GenX exposure at 0.4 and 4 µg/L prior to differentiation induced persistent changes in nuclear morphology and chromatin arrangements, manifested specifically in the facultative repressive marker H3K27me3. We also observed impaired neuronal network, increased calcium activity along with alterations in Tyrosine hydroxylase (TH) and α-Synuclein (αSyn) after prior exposure to GenX. Collectively, our results identified neurotoxicity of low-dose GenX exposure in human DA-like neurons following a developmental exposure scheme. The observed changes in neuronal characteristics suggest GenX as a potential neurotoxin and risk factor for Parkinson's disease.

Integrated surveillance strategy to support the prevention of neural tube defects through food fortification with folic acid: the experience of Costa Rica.

PURPOSE: (1) To describe how Costa Rica implemented an integrated surveillance strategy of folate deficiency, neural tube defects (NTDs) prevalence, NTDs-associated infant mortality rate (NTDs-IMR), and folic acid food fortification (FAFF), to support with evidence NTDs prevention policies; (2) to disseminate updated data from monitoring programs. METHODS: We performed a cross-sectional analysis, using the databases of national surveillance systems for NTDs outcomes to compare NTDs-prevalence and NTDs-IMR observed in the pre-fortification (1987-1998) and post-fortification (2010-2020) periods. In addition, using data from FAFF monitoring program (2010-2020), means of folic acid concentration (mg/kg) and folic acid daily intake (µg/day) were calculated for each fortified food (corn and wheat flour, rice and milk), as well as its contribution to folic acid estimated average requirement (EAR). RESULTS: After FAFF Costa Rica showed a decrease of 84% in folic acid deficiency in women of childbearing age, as well as a 53% decrease in the prevalence of NTDs, falling from 11.82/10,000 to 5.52/10,000 livebirths. In addition, there was a 76% reduction in the NTDs-IMR from 77.01/100,000 to 18.66/100,000 livebirths. Between 2010 and 2020, all fortified foods provided an average contribution of 119% of the EAR of folic acid in the population. CONCLUSION: To reduce NTD risk, an integrated surveillance strategy is essential not only to base prevention strategies on evidence, but also to demonstrate their impact and improve interventions over time. The experience in Costa Rica provides evidence that this type of surveillance is feasible to be implemented in developing countries.

Intraurban Geographic and Socioeconomic Inequalities of Mortality in Four Cities in Colombia.

Mortality inequalities have been described across Latin American countries, but less is known about inequalities within cities, where most populations live. We aimed to identify geographic and socioeconomic inequalities in mortality within the urban areas of four main cities in Colombia. We analyzed mortality due to non-violent causes of diseases in adults between 2015 and 2019 using census sectors as unit of analysis in Barranquilla, Bogotá, Cali, and Medellín. We calculated smoothed Bayesian mortality rates as main health outcomes and used concentration indexes (CInd) for assessing inequalities using the multidimensional poverty index (MPI) as the socioeconomic measure. Moran eigenvector spatial filters were calculated to capture the spatial patterns of mortality and then used in multivariable models of the association between mortality rates and quintiles of MPI. Social inequalities were evident but not consistent across cities. The most disadvantaged groups showed the highest mortality rates in Cali. Geographic inequalities in mortality rates, regardless of the adults and poverty distribution, were identified in each city, suggesting that other social, environmental, or individual conditions are impacting the spatial distribution of mortality rates within the four cities.

Toxicidad por marcador corneal en Femto-LASIK. Reporte de caso / Toxicity by corneal marker in Femto-LASIK. Case report

La violeta de genciana es un colorante orgánico sintético, descrito por primera vez por Charles Lauth en 1861. Tiene propiedades antibacterianas, antifúngicas, antihelmínticas, antitripanosómicas, antiantiogénicas y antitumorales. Tiene diversos mecanismos de acción, entre los que principalmente se encuentra bloquear la actividad de las nicotinamida adenina dinucleótido fosfato oxidasas, evitando la generación de radicales superoxidativos y la posterior inflamación. En los últimos años se ha utilizado en marcadores para procedimientos en diferentes especialidades médicas, incluidos los de oftalmología. La tinta de violeta de genciana se describe por el fabricante como no tóxica, sin embargo existe evidencia clínica y experimental que sugiere que puede ser tóxica para el endotelio corneal y puede llegar a generar queratitis lamelar difusa posterior a LASIK y Femto-LASIK. Se describe el caso de una paciente de 23 años de edad, que presentó diversas patologías en la córnea después del uso de marcador quirúrgico durante procedimiento refractivo Femto-LASIK.

Gentian violet is a synthetic and organic dye. First described by Charles Lauth in 1861. It has antibacterial, antifungal, anthelmintic, antitrypanosomal, antiangiogenic, and antitumoral properties. It has various mechanisms of action, among which is mainly blocking the activity of nicotinamide adenine dinucleotide phosphate oxidases, preventing the generation of superoxidative radicals and subsequent inflammation. In recent years, it has been used as markers for procedures in different medical specialties, including ophthalmology. Gentian violet ink is described by the manufacturer as non-toxic, however, there is clinical and experimental evidence suggesting that it may be toxic to the corneal endothelium and may cause diffuse lamellar keratitis after LASIK and Femto-LASIK. The case about a 23-year-old female patient who presented various pathologies in the cornea after the use of a surgical marker during the Femto-LASIK refractive procedure is described.

Experiencia de downstaging versus criterios de Milán para trasplante hepático por carcinoma hepatocelular en una cohorte prospectiva / Experience with downstaging versus Milan criteria for liver transplantation in patients with hepatocellular carcinoma in a prospective cohort

Introducción. El acceso al trasplante hepático (TH) en pacientes con carcinoma hepatocelular (CHC) se basa en la aplicación de criterios morfológicos rigurosos estipulados desde 1996, co-nocidos como criterios de Milán. Una de las estrategias descritas para expandir estos criterios se conoce como downstaging (reducción del estadiaje tumoral mediante terapias locorregionales). El objetivo de este estudio fue describir el comportamiento postrasplante de pacientes con CHC que ingresaron dentro de los parámetros de Milán, comparado con el de aquellos pacientes llevados a terapia de downstaging en un centro colombiano. Metodología. Se incluyeron pacientes adultos con cirrosis hepática (CH) y CHC que fueron llevados a TH en el Hospital Pablo Tobón Uribe, entre julio de 2012 a septiembre de 2021. Como desenlace principal se definió recurrencia y tiempo de recurrencia de la enfermedad tumoral, muerte por todas las causas y tiempo al fallecimiento. Se evaluaron las características sociodemográficas y clínicas de cada grupo. Se incluyeron scores pronósticos de recurrencia de la enfermedad tumoral. Resultados. Se trasplantaron 68 pacientes con CH y CHC, 50 (73,5 %) eran hombres y la edad promedio fue 59 años; 51 pacientes (75 %) cumplían con los criterios de Milán y 17 (25 %) fueron llevados a terapia de downstaging previo al TH. No hubo diferencias significativas en la supervivencia global y supervivencia libre de trasplante entre los dos grupos evaluados, p=0,479 y p=0,385, respectivamente. Tampoco hubo diferencia significativa en la recurrencia de la enfermedad tumoral entre ambos grupos (p=0,81). En total hubo 7 casos de recurrencia tumoral (10,2 %) y 11 casos de muerte (16,2 %). Conclusiones. No se encontraron diferencias significativas en recurrencia y mortalidad entre los pacientes que cumplían los criterios de Milán y los trasplantados luego de la terapia de downstaging, en un tiempo de se-guimiento de 53 meses hasta el último control posterior al trasplante hepático. Esta sería la primera evaluación prospectiva de un protocolo de downstaging para CHC en Colombia.

Introduction. Access to liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) is based on the application of rigorous morphological criteria stipulated since 1996, known as the Milan criteria. One of the strategies described to expand these criteria is known as downstaging (tu-mor staging reduction through locoregional therapies). The objective of this study was to describe the post-transplant performance of patients with HCC who were admitted within the Milan parameters, compared with those of patients taken to downstaging therapy, in a Colombian center. Methodolo-gy. Adult patients with cirrhosis and HCC that received LT between July 2012 and September 2021 at the Pablo Tobón Uribe Hospital were included. The main outcome was defined as recurrence and time to recurrence of the tumor disease, death from all causes, and time to death. The socio-demographic and clinical characteristics of each group were evaluated. Tumor disease recurrence prognostic scores were included. Results. Sixty-eight patients with cirrhosis and HCC received LT in the time frame, 50 (73.5%) were men and the mean age was 59 years. Fifty-one patients were trans-planted (75%) fulfilling Milan criteria, and 17 (25%) patients received downstaging therapies before LT. There were no significant differences in overall survival and transplant-free survival between the two groups, p=0.479 and p=0.385, respectively. There was also no significant difference in the recurrence of the tumor disease between both groups (p=0.81). In total there were 7 tumoral recurrences (10.2%) and 11 deaths (16.2%). Conclusions. There were no differences in recurrence and survival between patients transplanted fulfilling Milan criteria and those receiving downstaging therapies, following a mean time of 53 months after LT. This is the first prospective evaluation of the downstaging protocol in Colombia.

Nanosafety Analysis of Graphene-Based Polyester Resin Composites on a Life Cycle Perspective.

The use, production, and disposal of engineering nanomaterials (ENMs), including graphene-related materials (GRMs), raise concerns and questions about possible adverse effects on human health and the environment, considering the lack of harmonized toxicological data on ENMs and the ability of these materials to be released into the air, soil, or water during common industrial processes and/or accidental events. Within this context, the potential release of graphene particles, their agglomerates, and aggregates (NOAA) as a result of sanding of a battery of graphene-based polyester resin composite samples intended to be used in a building was examined. The analyzed samples were exposed to different weathering conditions to evaluate the influence of the weathering process on the morphology and size distribution of the particles released. Sanding studies were conducted in a tailored designed sanding bench connected to time and size resolving measurement devices. Particle size distributions and particle number concentration were assessed using an optical particle counter (OPC) and a condensation particle counter (CPC), respectively, during the sanding operation. A scanning electron microscope/energy dispersive X-ray (SEM/EDX) analysis was performed to adequately characterize the morphology, size, and chemical composition of the released particles. A toxicity screening study of pristine and graphene-based nanocomposites released using the aquatic macroinvertebrate Daphnia magna and relevant human cell lines was conducted to support risk assessment and decision making. The results show a significant release of nanoscale materials during machining operations, including differences attributed to the % of graphene and weathering conditions. The cell line tests demonstrated a higher effect in the human colon carcinoma cell line Caco2 than in the human fibroblasts (A549 cell line), which means that composites released to the environment could have an impact on human health and biota.

Pre-differentiation exposure of PFOA induced persistent changes in DNA methylation and mitochondrial morphology in human dopaminergic-like neurons.

Perfluorooctanoic acid (PFOA) is abundant in environment due to its historical uses in consumer products and industrial applications. Exposure to low doses of PFOA has been associated with various disease risks, including neurological disorders. The underlying mechanism, however, remains poorly understood. In this study, we examined the effects of low dose PFOA exposure at 0.4 and 4 µg/L on the morphology, epigenome, mitochondrion, and neuronal markers of dopaminergic (DA)-like SH-SY5Y cells. We observed persistent decreases in H3K4me3, H3K27me3 and 5 mC markers in nucleus along with alterations in nuclear size and chromatin compaction percentage in DA-like neurons differentiated from SH-SY5Y cells exposed to 0.4 and 4 µg/L PFOA. Among the selected epigenetic features, DNA methylation pattern can be used to distinguish between PFOA-exposed and naïve populations, suggesting the involvement of epigenetic regulation. Moreover, DA-like neurons with pre-differentiation PFOA exposure exhibit altered network connectivity, mitochondrial volume, and TH expression, implying impairment in DA neuron functionality. Collectively, our results revealed the prolonged effects of developmental PFOA exposure on the fitness of DA-like neurons and identified epigenome and mitochondrion as potential targets for bearing long-lasting changes contributing to increased risks of neurological diseases later in life.

Atrazine exposure in zebrafish induces aberrant genome-wide methylation.

Atrazine (ATZ) is the second most common agricultural herbicide used in the United States and is an endocrine disrupting chemical (EDC). Developmental exposure to ATZ can lead to significant behavioral and morphological alterations in exposed animals and their progeny suggesting the involvement of an epigenetic mechanism. Specific epigenetic mechanisms responsible for these alterations, however, are yet to be elucidated. In this study, we exposed zebrafish embryos to 0, 0.3, 3, or 30 ppb (µg/L) of ATZ from 1 to 72 h post fertilization (hpf). Chemical exposure was ceased and zebrafish maintained until 9 months post fertilization (mpf), when whole-genome bisulfite sequencing (WGBS) was performed to assess the effects of embryonic ATZ exposure on DNA methylation in female fish brains. The number of differentially methylated genes (DMGs) increased with increasing treatment concentration. DMGs were enriched in neurological pathways with extensive methylation changes consistently observed in neuroendocrine pathways. Specifically, DMGs with methylation changes in promoter regions showed hypomethylation in estrogen receptor signaling and hypermethylation in androgen signaling. DMGs with methylation changes in genebody were primarily enriched for mitochondrion-related pathways associated with healthy aging. Integrated analysis with transcriptomic data at 9 mpf exhibited a similar trend identifying CABLES1 and NDUFA4 as shared targets at all concentrations. We then compared the predicted upstream regulators of transcriptomic changes with DMGs and identified CALML3 as a common upstream regulator at both 0.3 and 30 ppb that exhibit significant methylation changes. Collectively, our study identified long-lasting DNA methylation changes in genome after embryonic ATZ exposure and elucidated potential gene targets whose aberrant methylation features may drive alterations in gene transcription in long-term.

Consensus in acute myeloid leukemia in Mexico.

Acute myeloid leukemia (AML) comprises a heterogeneous group of hematopoietic cell neoplasms of myeloid lineage that arise from the clonal expansion of their precursors in the bone marrow, interfering with cell differentiation, leading to a syndrome of bone marrow failure. AML is a consequence of genetic and epigenetic changes (point mutations, gene rearrangements, deletions, amplifications, and arrangements in epigenetic changes that influence gene expression) in hematopoietic precursor cells, which create a clone of abnormal cells that are capable of proliferating but cannot differentiate into mature hematopoietic cells or undergo programmed cell death. The diagnosis requires more than 20% myeloid blasts in the bone marrow and certain cytogenic abnormalities. Treatment will depend on age, comorbidities, and cytogenetic risk among the most frequent.

La leucemia mieloide aguda (LMA) comprende un grupo heterogéneo de neoplasias de células hematopoyéticas de linaje mieloide que surgen de la expansión clonal de sus precursores en la médula ósea, interfiriendo con la diferenciación celular, lo que conlleva a un síndrome de falla medular. La LMA es una consecuencia de cambios genéticos y epigenéticos (mutaciones puntuales, rearreglos de genes, deleciones, amplificaciones y arreglos en cambios epigenéticos que influyen en la expression del gen) en las células hematopoyéticas precursoras, la cual crea una clona de células anormales que son capaces de proliferar, pero no se pueden diferenciar en células hematopoyéticas maduras ni sufrir una muerte celular programada. El diagnostic requiere más del 20% de blastos mieloides en médula ósea y ciertas anormalidades citogénicas. El tratamiento dependerá de la edad, comorbilidades, riesgo citogenético entre las más frecuentes.

Development and application of novel BiFC probes for cell sorting based on epigenetic modification.

The epigenetic signature of cancer cells varies with disease progression and drug treatment, necessitating the study of these modifications with single cell resolution over time. The rapid detection and sorting of cells based on their underlying epigenetic modifications by flow cytometry can enable single cell measurement and tracking to understand tumor heterogeneity and progression warranting the development of a live-cell compatible epigenome probes. In this work, we developed epigenetic probes based on bimolecular fluorescence complementation (BiFC) and demonstrated their capabilities in quantifying and sorting cells based on their epigenetic modification contents. The sorted cells are viable and exhibit distinctive responses to chemo-therapy drugs. Notably, subpopulations of MCF7 cells with higher H3K9me3 levels are more likely to develop resistance to Doxorubicin. Subpopulations with higher 5mC levels, on the other hand, tend to be more responsive. Overall, we report for the first time, the application of novel split probes in flow cytometry application and elucidated the potential role of 5mC and H3K9me3 in determining drug responses.

Consenso de leucemia mieloide aguda en México / Mexican consensus in acute myeloid leukemia in Mexico

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Abstract Acute myeloid leukemia (AML) comprises a heterogeneous group of hematopoietic cell neoplasms of myeloid lineage that arise from the clonal expansion of their precursors in the bone marrow, interfering with cell differentiation, leading to a syndrome of bone marrow failure. AML is a consequence of genetic and epigenetic changes (point mutations, gene rearrangements, deletions, amplifications, and arrangements in epigenetic changes that influence gene expression) in hematopoietic precursor cells, which create a clone of abnormal cells that are capable of proliferating but cannot differentiate into mature hematopoietic cells or undergo programmed cell death. The diagnosis requires more than 20% myeloid blasts in the bone marrow and certain cytogenic abnormalities. Treatment will depend on age, comorbidities, and cytogenetic risk among the most frequent.

Evaluation of Signaling Pathways Profiling in Human Dermal Endothelial Cells Treated by Snake Venom Cysteine-Rich Secretory Proteins (svCRiSPs) from North American Snakes Using Reverse Phase Protein Array (RPPA).

Cysteine-Rich Secretory Proteins (CRiSPs) are typically found in many snake venoms; however, the role that these toxins play in the pathophysiology of snakebites is still unclear. Herein, we compared the effects of snake venom CRiSPs (svCRiSPs) from the most medically important species of North American snakes on endothelial cell permeability and vascular permeability. We used reverse phase protein array (RPPA) to identify key signaling molecules on human dermal lymphatic (HDLECs) and blood (HDBECs) endothelial cells treated with svCRiSPs. The results showed that Css-CRiSP isolated from Crotalus scutulatus scutulatus and App-CRiSP from Agkistrodon piscivorus piscivorus are the most potent causes of increase vascular and endothelial permeability in comparison with other svCRiSPs used in this study. We examined the protein expression levels and their activated phosphorylation states in HDLECs and HDBECs induced by App-CRiSP and Css-CRiSP using RPPA. Interestingly, both App-CRiSP and Css-CRiSP induced caveolin-1 expression in HDBECs. We also found that stimulating HDBECs with Css-CRiSP and App-CRiSP significantly induced the phosphorylation of mTOR and Src, respectively. In HDLECs, Css-CRiSP significantly downregulated the expression of N-Cadherin and phospholipase C-gamma, while App-CRiSP significantly enhanced Akt and JNK phosphorylation. These results suggest that the increased endothelial permeability in HDLECs and HDBECs by Css-CRiSP and App-CRiSP may occur through different pathways.

Mexican Consensus on Hodgkin's Lymphoma.

Hodgkin's lymphoma is due to the clonal transformation of cells originating from B lymphocytes, generating the pathognomonic binucleate Reed-Sternberg cells. Hodgkin's lymphoma is a B cell disease with a bimodal distribution, with higher incidence in adolescence and the third decade of life, showing a second peak in people over 55 years of age. Classic Hodgkin lymphoma cells routinely undergo gene expression reprogramming, as they lose the expression of most of the typical B-cell genes and acquire the expression of multiple genes that are typical of other types of cells in the immune system. The treatment algorithm will depend on whether it is classic or predominantly lymphocytic HL, if it is early stage with unfavorable prognostic markers or not, the initial management regimen, and whether there is bulky disease, among the most relevant variables.

El linfoma de Hodgkin (LH) se debe a la transformación clonal de células originadas en los linfocitos B, lo que genera las células binucleadas patognomónicas de Reed-Sternberg. El LH es una enfermedad de células B con una distribución bimodal, con mayor incidencia en la adolescencia y la tercera década de la vida y un segundo pico en personas mayores de 55 años. Las células del LH clásico habitualmente sufren una reprogramación de la expresión génica, ya que pierden la expresión de la mayoría de los genes típicos de las células B y han adquirido la expresión de múltiples genes que son típicos de otros tipos de células del sistema inmunitario. El algoritmo de tratamiento dependerá si se trata de LH clásico o de predominio linfocítico, si es un estadio temprano con marcadores de pronóstico desfavorables o no, el esquema inicial de manejo y si existe enfermedad voluminosa, entre las variables más relevantes.

Mexican consensus on Hodgkin's lymphoma.

El linfoma de Hodgkin (LH) se debe a la transformación clonal de células originadas en los linfocitos B, lo que genera las células binucleadas patognomónicas de Reed-Sternberg. El LH es una enfermedad de células B con una distribución bimodal, con mayor incidencia en la adolescencia y la tercera década de la vida y un segundo pico en personas mayores de 55 años. Las células del LH clásico habitualmente sufren una reprogramación de la expresión génica, ya que pierden la expresión de la mayoría de los genes típicos de las células B y han adquirido la expresión de múltiples genes que son típicos de otros tipos de células del sistema inmunitario. El algoritmo de tratamiento dependerá si se trata de LH clásico o de predominio linfocítico, si es un estadio temprano con marcadores de pronóstico desfavorables o no, el esquema inicial de manejo y si existe enfermedad voluminosa, entre las variables más relevantes.Hodgkin's lymphoma (HL) is due to the clonal transformation of cells originating from B lymphocytes, generating the pathognomonic binucleate Reed-Sternberg cells. HL is a B cell disease with a bimodal distribution, with higher incidence in adolescence and the third decade of life, showing a second peak in people over 55 years of age. Classic Hodgkin lymphoma cells routinely undergo gene expression reprogramming, as they lose the expression of most of the typical B-cell genes and acquire the expression of multiple genes that are typical of other types of cells in the immune system. The treatment algorithm will depend on whether it is classic or predominantly lymphocytic HL, if it is early stage with unfavorable prognostic markers or not, the initial management regimen, and whether there is bulky disease, among the most relevant variables.