Bifidobacterium longum and Chlorella sorokiniana Combination Modulates IFN-γ, IL-10, and SOCS3 in Rotavirus-Infected Cells.

Rotavirus is the main cause of acute diarrhea in children up to five years of age. In this regard, probiotics are commonly used to treat or prevent gastroenteritis including viral infections. The anti-rotavirus effect of Bifidobacterium longum and Chlorella sorokiniana, by reducing viral infectivity and improving IFN-type I response, has been previously reported. The present study aimed to study the effect of B. longum and/or C. sorokiniana on modulating the antiviral cellular immune response mediated by IFN-γ, IL-10, SOCS3, STAT1, and STAT2 genes in rotavirus-infected cells. To determine the mRNA relative expression of these genes, HT-29 cells were treated with B. longum and C. sorokiniana alone or in combination, followed by rotavirus infection. In addition, infected cells were treated with B. longum and/or C. sorokiniana. Cellular RNA was purified, used for cDNA synthesis, and amplified by qPCR. Our results demonstrated that the combination of B. longum and C. sorokiniana stimulates the antiviral cellular immune response by upregulating IFN-γ and may block pro-inflammatory cytokines by upregulating IL-10 and SOCS3. The results of our study indicated that B. longum, C. sorokiniana, or their combination improve antiviral cellular immune response and might modulate pro-inflammatory responses.

The Relationship Between CYP46A1 Polymorphism and Suicide Risk: A Preliminary Investigation.

Suicide is a global public health issue, with a particularly high incidence in individuals suffering from Major Depressive Disorder (MDD). The role of cholesterol in suicide risk remains controversial, prompting investigations into genetic markers that may be implicated. This study examines the association between CYP46A1 polymorphisms, specifically SNPs rs754203 and rs4900442, and suicide risk in a Mexican MDD patient cohort. Our study involved 188 unrelated suicide death victims, 126 MDD patients, and 144 non-suicidal controls. Genotypic and allelic frequencies were assessed using the Real Time-polymerase chain reaction method, and associations with suicide risk were evaluated using chi-square tests. The study revealed significant differences in allelic and genotypic frequencies in rs754203 SNP between suicide death and controls. The CYP46A1 rs754203 genotype G/G was significantly linked with suicide, and the G allele was associated with a higher risk of suicide (OR = 1.370, 95% CI = 1.002-1.873). However, we did not observe any significant differences in genotype distribution or allele frequencies of CYP46A1 rs4900442. Our study suggests that carriers of the CYP46A1 rs754203 G allele (A/G + G/G) may play a role in suicidal behavior, especially in males. Our findings support that the CYP46A1 gene may be involved in susceptibility to suicide, which has not been investigated previously. These results underscore the importance of further research in different populations to elucidate the genetic underpinnings of the role of CYP46A1 in suicide risk and to develop targeted interventions for at-risk populations.

MiR-21 Regulates Growth and Migration of Cervical Cancer Cells by RECK Signaling Pathway.

Expression of miR-21 has been found to be altered in almost all types of cancers, and it has been classified as an oncogenic microRNA. In addition, the expression of tumor suppressor gene RECK is associated with miR-21 overexpression in high-grade cervical lesions. In the present study, we analyze the role of miR-21 in RECK gene regulation in cervical cancer cells. To identify the downstream cellular target genes of upstream miR-21, we silenced endogenous miR-21 expression using siRNAs. We analyzed the expression of miR-21 and RECK, as well as functional effects on cell proliferation and migration. We found that in cervical cancer cells, there was an inverse correlation between miR-21 expression and RECK mRNA and protein expression. SiRNAs to miR-21 increased luciferase reporter activity in construct plasmids containing the RECK-3'-UTR microRNA response elements MRE21-1, MRE21-2, and MRE21-3. The role of miR-21 in cell proliferation was also analyzed, and cancer cells transfected with siRNAs exhibited a markedly reduced cell proliferation and migration. Our findings indicate that miR-21 post-transcriptionally down-regulates the expression of RECK to promote cell proliferation and cell migration inhibition in cervical cancer cell survival. Therefore, miR-21 and RECK may be potential therapeutic targets in gene therapy for cervical cancer.

Study protocol and rationale of "the UP project": evaluating the effectiveness of active breaks on health indicators in desk-based workers.

Background: Excessive sedentary time has been negatively associated with several health outcomes, and physical activity alone does not seem to fully counteract these consequences. This panorama emphasizes the essential of sedentary time interruption programs. "The Up Project" seeks to assess the effectiveness of two interventions, one incorporating active breaks led by a professional and the other utilizing a computer application (self-led), of both equivalent duration and intensity. These interventions will be compared with a control group to evaluate their impact on physical activity levels, sedentary time, stress perception, occupational pain, and cardiometabolic risk factors among office workers. Methods: This quasi-experimental study includes 60 desk-based workers from universities and educational institutes in Valparaiso, Chile, assigned to three groups: (a) booster breaks led by professionals, (b) computer prompts that are unled, and (c) a control group. The intervention protocol for both experimental groups will last 12 weeks (only weekdays). The following measurements will be performed at baseline and post-intervention: cardiometabolic risk based on body composition (fat mass, fat-free mass, and bone mass evaluated by DXA), waist circumference, blood pressure, resting heart rate, and handgrip strength. Physical activity and sedentary time will be self-reported and device-based assessed using accelerometry. Questionnaires will be used to determine the perception of stress and occupational pain. Discussion: Governments worldwide are addressing health issues associated with sedentary behavior, particularly concerning individuals highly exposed to it, such as desk-based workers. Despite implementing certain strategies, there remains a noticeable gap in comprehensive research comparing diverse protocols. For instance, studies that contrast the outcomes of interventions led by professionals with those prompted by computers are scarce. This ongoing project is expected to contribute to evidence-based interventions targeting reduced perceived stress levels and enhancing desk-based employees' mental and physical well-being. The implications of these findings could have the capacity to lay the groundwork for future public health initiatives and government-funded programs.

Adolescents with a Favorable Mediterranean-Style-Based Pattern Show Higher Cognitive and Academic Achievement: A Cluster Analysis-The Cogni-Action Project.

A Mediterranean diet (MedDiet) has emerged as a crucial dietary choice, not only in attenuating various adolescents' metabolic health issues but it has also been associated with improved cognitive and academic achievement. However, few studies have established patterns of food consumption linked to both cognitive and academic achievement in adolescents living in a developing country with non-Mediterranean-based food. Methods: This cross-sectional study included 1296 Chilean adolescents (50% girls) aged 10-14 years. The MedDiet Quality Index was used to assess adherence to the MedDiet in children and adolescents. Through cluster analysis, four distinct dietary patterns were identified: Western diet (WD = 4.3%); low fruit and vegetables, high-sugar diet (LFV-HSD = 28.2%); low fruit and vegetables, low-sugar diet (LFV-LSD = 42.2%); and the MedDiet (25.3%). A mixed-model analysis was conducted to compare these clusters and their relationships with cognitive and academic achievements. Principal component analysis was performed to identify four primary cognitive domains: working memory, cognitive flexibility, inhibitory control, and fluid reasoning. Academic achievement was determined with five school subjects (Language, English, Mathematics, Science, and History) and included the Academic-PISA score derived from the mean scores in Language, Mathematics, and Science. Results: A marked difference was observed between the four clusters, which was mainly related to the consumption of sugar, ultra-processed foods, fruits, and vegetables. According to cognitive performance, the MedDiet group showed higher performance across all domains than the LFV-HSD, LFV-LSD, and WD groups. Regarding academic achievement, the WD underperformed in all analyses compared to the other groups, while the MedDiet was the unique profile that achieved a positive difference in all academic subjects compared to the WD and LFV-HSD groups (p < 0.05). Conclusions: These findings suggest that higher adherence to Mediterranean-style-based patterns and better food quality choices are associated with improved cognitive and academic achievements.

Comprehensive analysis of right fascicular and right bundle branch blocks: A multi-center study.

Electrocardiographic patterns of right bundle branch and fascicular blocks were comprehensively analyzed in a two-phase study. The research aimed to address the scarcity of literature and the absence of standardized diagnostic criteria for these conditions. It revealed a weak correlation between the cardiac axis and age and highlighted the high misdiagnosis rate of these blocks. Furthermore, it discussed the challenges in fulfilling existing diagnostic criteria. The study emphasizes the need for a more precise understanding of right ventricular conduction disorders and the importance of developing robust diagnostic criteria.

Complementing Cell Taxonomies with a Multicellular Analysis of Tissues.

The application of single-cell molecular profiling coupled with spatial technologies has enabled charting of cellular heterogeneity in reference tissues and in disease. This new wave of molecular data has highlighted the expected diversity of single-cell dynamics upon shared external queues and spatial organizations. However, little is known about the relationship between single-cell heterogeneity and the emergence and maintenance of robust multicellular processes in developed tissues and its role in (patho)physiology. Here, we present emerging computational modeling strategies that use increasingly available large-scale cross-condition single-cell and spatial datasets to study multicellular organization in tissues and complement cell taxonomies. This perspective should enable us to better understand how cells within tissues collectively process information and adapt synchronized responses in disease contexts and to bridge the gap between structural changes and functions in tissues.

Novices' learning curve in single-port surgery using three surgical training programs.

BACKGROUND: The objective of this study was to evaluate the novices' learning curves and proficiency level reached in laparoendoscopic single-site (LESS) surgery using three surgical training programs. MATERIAL AND METHODS: Participants were randomly divided into three groups, who trained in a specific practice regimen for 12 days using a laparoscopic box simulator and three tasks. Group A trained in three stages using conventional laparoscopic surgery (CLS) with straight instruments, and LESS with straight and articulating instruments for four days each. Group B trained in two stages in LESS with straight and articulating instruments for six days each. Group C trained only in LESS with articulating instruments exclusively for all 12 days. Performance was registered daily during the 12 days to evaluate the participants' progress. RESULTS: Pre- and post-training analysis of the three groups showed significant differences in performance, denoting the significant improvement in their LESS skills, with no difference between the groups. Group C reached a high level of technical competence with their specific training program in LESS, obtaining a lower asymptote and slow learning rate. CONCLUSION: Specific training programs in LESS settings using articulated instruments showed a slower learning rate than the other programs but better proficiency in the technique with the best surgical performance.

Asociación entre condición física y fase angular en el adulto mayor: un estudio piloto / Association between physical fitness and angular phase in older adults: a pilot study / Associação entre condição física e fase angular em idosos: um estudo piloto

El diagnóstico por bioimpedancia (BIA) y el ángulo de fase (AnF), como indicador, permiten monitorear el estado físico, de salud y nutricional en adultos mayores. El objetivo de este estudio fue establecer la relación entre la condición física y valores de fase angular por bioimpedancia en un grupo de adultos mayores sedentarios. Participaron voluntariamente 24 adultos mayores sedentarios (21 mujeres y 3 hombres). A cada participante se les midió bioimpedancia, fuerza de presión manual y test de 6 minutos del Senior Fitness Test (SFT). Posteriormente se analizaron los resultados, correlacionando el ángulo de fase (AnF) y condición física cardiorrespiratoria según sexo y el AnF con la fuerza de presión manual. El 71% presentó una media de AnF por debajo de la referencia (4,5º ± 0,4), específicamente, el 67% de los hombres y el 62% de las mujeres. La correlación entre AnF y capacidad física cardiorrespiratoria arrojó un valor de R2= 0,50; p<0,0001. La asociación entre AnF y fuerza de presión manual fue de R2=0,35; p=0,0023. Se encontró una relación significativa entre una prueba de condición física cardiorrespiratoria y AnF y entre la fuerza de presión manual y AnF. Es de importancia clínica incluir parámetros objetivos de valoración celular en adultos mayores como el AnF.

The diagnosis by bioimpedance (BIA) and the phase angle (PhA) are indicators, that allow monitoring of the physical health and nutritional status of older adults. The objective of this study was to establish the relationship between physical fitness and phase angle values by bioimpedance in a group of sedentary older adults. 24 elderly sedentary volunteers participated (21 women and 3 men). Each participant underwent bioimpedance, manual dynamometry, and the 6-minute Senior Fitness Test (SFT). Subsequently, the results were analyzed, making a correlation between PhA and cardiorespiratory physical condition, another between PhA and cardiorespiratory physical condition according to sex and finally an association between PhA and handgrip strength. R71% presented a PhA mean below the reference (4.5º ± 0.4), specifically 67% of men and 62% of women. The correlation between PhA and cardiorespiratory fitness showed a value of R2= 0.50; p<0.0001. The association between PhA and handgrip strength was R2=0.35; p=0.0023. A significant relationship was found between a cardiorespiratory fitness test and PhA and between handgrip strength and PhA. It is of clinical importance to include objective cellular assessment parameters in older adults such as PhA.

O diagnóstico por bioimpedância (BIA) e ângulo de fase (AnF), como indicador, permitem monitorar o estado físico, de saúde e nutricional de idosos. O objetivo deste estudo foi estabelecer a relação entre a condição física e os valores da fase angular por bioimpedância em um grupo de idosos sedentários. Participaram voluntariamente 24 idosos sedentários (21 mulheres e 3 homens). Cada participante foi medido bioimpedância, força de pressão manual e teste de 6 minutos do Senior Fitness Test (SFT). Posteriormente, os resultados foram analisados, correlacionando o ângulo de fase (AnF) e a condição física cardiorrespiratória de acordo com o sexo e o AnF com a força de pressão manual. 71% apresentaram média do LAn abaixo da referência (4,5º ± 0,4), sendo 67% dos homens e 62% das mulheres. A correlação entre o LAn e a aptidão cardiorrespiratória deu um valor de R2= 0,50; p<0,0001. A associação entre LAn e força de pressão manual foi R2=0,35; p=0,0023. Encontrou-se relação significativa entre teste de aptidão cardiorrespiratória e NF e entre força de pressão manual e NF. É de importância clínica incluir parâmetros objetivos de avaliação celular em adultos mais velhos, como AnF.

Multicellular factor analysis of single-cell data for a tissue-centric understanding of disease.

Biomedical single-cell atlases describe disease at the cellular level. However, analysis of this data commonly focuses on cell-type-centric pairwise cross-condition comparisons, disregarding the multicellular nature of disease processes. Here, we propose multicellular factor analysis for the unsupervised analysis of samples from cross-condition single-cell atlases and the identification of multicellular programs associated with disease. Our strategy, which repurposes group factor analysis as implemented in multi-omics factor analysis, incorporates the variation of patient samples across cell-types or other tissue-centric features, such as cell compositions or spatial relationships, and enables the joint analysis of multiple patient cohorts, facilitating the integration of atlases. We applied our framework to a collection of acute and chronic human heart failure atlases and described multicellular processes of cardiac remodeling, independent to cellular compositions and their local organization, that were conserved in independent spatial and bulk transcriptomics datasets. In sum, our framework serves as an exploratory tool for unsupervised analysis of cross-condition single-cell atlases and allows for the integration of the measurements of patient cohorts across distinct data modalities.

Changes in the Proliferation of the Neural Progenitor Cells of Adult Mice Chronically Infected with Toxoplasma gondii.

During Toxoplasma gondii chronic infection, certain internal factors that trigger the proliferation of neural progenitor cells (NPCs), such as brain inflammation, cell death, and changes in cytokine levels, are observed. NPCs give rise to neuronal cell types in the adult brain of some mammals. NPCs are capable of dividing and differentiating into a restricted repertoire of neuronal and glial cell types. In this study, the proliferation of NPCs was evaluated in CD-1 adult male mice chronically infected with the T. gondii ME49 strain. Histological brain sections from the infected mice were evaluated in order to observe T. gondii tissue cysts. Sagittal and coronal sections from the subventricular zone of the lateral ventricles and from the subgranular zone of the hippocampal dentate gyrus, as well as sagittal sections from the rostral migratory stream, were obtained from infected and non-infected mice previously injected with bromodeoxyuridine (BrdU). A flotation immunofluorescence technique was used to identify BrdU+ NPC. The scanning of BrdU+ cells was conducted using a confocal microscope, and the counting was performed with ImageJ® software (version 1.48q). In all the evaluated zones from the infected mice, a significant proliferation of the NPCs was observed when compared with that of the control group. We concluded that chronic infection with T. gondii increased the proliferation of NPCs in the three evaluated zones. Regardless of the role these cells are playing, our results could be useful to better understand the pathogenesis of chronic toxoplasmosis.

Expanding the coverage of regulons from high-confidence prior knowledge for accurate estimation of transcription factor activities.

Gene regulation plays a critical role in the cellular processes that underlie human health and disease. The regulatory relationship between transcription factors (TFs), key regulators of gene expression, and their target genes, the so called TF regulons, can be coupled with computational algorithms to estimate the activity of TFs. However, to interpret these findings accurately, regulons of high reliability and coverage are needed. In this study, we present and evaluate a collection of regulons created using the CollecTRI meta-resource containing signed TF-gene interactions for 1186 TFs. In this context, we introduce a workflow to integrate information from multiple resources and assign the sign of regulation to TF-gene interactions that could be applied to other comprehensive knowledge bases. We find that the signed CollecTRI-derived regulons outperform other public collections of regulatory interactions in accurately inferring changes in TF activities in perturbation experiments. Furthermore, we showcase the value of the regulons by examining TF activity profiles in three different cancer types and exploring TF activities at the level of single-cells. Overall, the CollecTRI-derived TF regulons enable the accurate and comprehensive estimation of TF activities and thereby help to interpret transcriptomics data.

Food Insecurity and Dental Caries in Rural Mexican Populations.

Objective: Food insecurity (FI) is a priority for government and health organizations. Over 95% of the world's population has a carious lesion or will develop one before death. This study evaluated the association between FI and oral health in two rural communities in Chiapas, Mexico. Methods: The study was conducted with patients attending an oral health campaign for dental checkups. Data were collected between April and August 2017 using the Latin-American and Caribbean Scale of Food Security (ELCSA) and the International Caries Detection and Assessment System (ICDAS). We included 209 participants from Siltepec and Huehuetan, Mexico; 67% were women. Results: The results of the ELCSA were mild FI in 43% (n = 91), moderate FI in 22% (n = 45), and severe FI (n = 6) in 3%; 32% had food security. The ICDAS results were initial decay with a mean of 6.22, moderate decay with a mean of 1.81, and extensive decay with a mean of 1.77. Conclusions: FI is associated with dental caries, and food-insecure individuals have a higher probability of severe dental caries. In this study, the FI level was lower than in other rural populations in Mexico. Identifying these individuals and addressing the factors related to FI can be useful in the rural communities.

Adult Diaphorina citri Biocontrol Using Hirsutella citriformis Strains and Gum Formulations.

Hirsutella citriformis Speare is the only entomopathogenic fungus that has been applied to control the hemipteran Diaphorina citri Kuwayama. However, the use of available commercial products under field conditions is limited due to conidia's shelf life and short environmental persistence. We have previously reported the citrus psyllid D. citri adults' biocontrol potential using H. citriformis strains. The aim of the present study was to evaluate different formulations based on H. citriformis (OP-Hir-3, OP-Hir-10, and OP-Hir-12 strains) conidia and gums as additives to improve D. citri adults' biocontrol, under laboratory, greenhouse, and field conditions, using Hirsutella gums as conidia stabilizers to improve their viability under environmental drought conditions and as insecticide. Laboratory bioassay results showed that the highest (p < 0.05) D. citri mortality was achieved using FOP-Hir-10GH (63.5%), followed by the Hirsutella gum control (42.2%). Under greenhouse conditions, adults' mortality reached up to 84.6% with FOP-Hir-12 and 49.0% with Hirsutella gum. In addition, we applied H. citriformis formulations under field conditions in a commercial citrus grove located in Tecomán, Colima, México, at 21.5 °C and 73.3% relative humidity (RH) in March and 25.7 °C and 72.5% RH in October 2022 and observed 67.3% and 94.0% mortality of D. citri adults, respectively. Hirsutella gum alone showed significant insecticidal activity against D. citri adults. In conclusion, this study demonstrated that Hirsutella gum functioned as additive to H. citriformis conidia formulations, improving D. citri adults' mortality and showing potential for this pest biocontrol in citrus orchards.

Prevalence of Oral Helicobacter pylori Infection in an Indigenous Community in Southwest Mexico.

Purpose: Epidemiological studies have been conducted to improve the health and economic quality of life of indigenous communities in Mexico. These studies have found that infections cause frequent health problems. Helicobacter pylori are responsible for conditions ranging from gastritis to stomach cancer. This study determined the prevalence of H. pylori in families from Siltepec, Chiapas, Mexico. Patient and Methods: Ninety-nine dental plaque samples from 36 families were studied. Real-time PCR was performed to detect H. pylori using previously reported primers. The Mann-Whitney U-test was used for the statistical analysis. According to the family role of H. pylori-positive individuals, the VacA s1/m1 genotype and CagA gene correlated. Results: The mother had the highest expression of VacA s1/m1-/cagA- with 19% (8/42), followed by the first child with 14.3% (6/42). The major roles for the vacA s1/m1+/cagA- were the mother and first child with 9.5% (4/42), followed by the remaining children with 4.8% (2/42). The vacA s1/m1-/cagA+ genotype was 7.1% (3/42) for the mother and 4.8% (2/42) for the father. Finally, the vacA s1/m1+/cagA+ genotype only appeared in the mother, son I, and son III with 2.4% (1/42). Conclusion: The vacA s1/m1/cagA genotypes predominated in the mother, suggesting potential transmission between the mother and child during the first years of life.

A comparative study between traditional and sports school uniforms on cardiorespiratory and muscular fitness and waist-height-to-ratio in adolescents.

Background: Improving health of children and adolescents is crucial for their overall development. Therefore, it is essential to explore factors that may influence their health at both the public health and school system levels. Objective: This study compares physical fitness components and waist-height-to-ratio (WHtR) in adolescents according to school uniforms, namely the traditional uniform (i.e., shirt and school necktie in boys and skirt and blouse in girls) and the sports uniform (i.e., polo shirts or t-shirts and sport or short trousers). Additionally, it seeks to investigate potential differences in these measures based on sex and school type (i.e., public, subsidized, and private). Methods: This cross-sectional study used data from the Chilean national learning outcome assessment system (SIMCE)-2014 and involved 8,030 adolescents. Cardiorespiratory fitness (CRF) and muscular fitness (MF) were measured. WHtR was assessed as a health cardiovascular indicator. Mixed models and ANCOVA were performed to compare uniform types, adjusting for multiple covariates. value of p and effect size (ES) was used to establish significant results. Results: Overall, sports uniforms (SU) were linked to higher CRF (p < 0.001) than the traditional uniform (TU). Boys from private schools wearing SU presented higher CRF (p = 0.016; ES = 0.37), and a positive trend was observed for MF (p = 0.645; ES = 0.21). In subsidized, a trend was found in CRF (p = 0.005; ES = 0.16). Girls wearing SU from private schools showed a positive trend in CRF (p = 0.167; ES = 0.28). Trends in WHtR were found in both sexes from private (p = 0.555; ES = 0.24; p = 0.444; ES = 0.25, respectively). Conclusion: Wearing SU seems a promissory alternative to promote healthy physical fitness and body composition at the educational level. However, the relationship between higher physical activity and CRF, MF, and lower WHtR due to SU must be verified. Finally, when deciding to implement this measure, special attention must be paid to boys from public schools and girls from all types of schools.

Bifidobacterium longum and Chlorella sorokiniana Improve the IFN Type I-Mediated Antiviral Response in Rotavirus-Infected Cells.

Probiotics are effective to treat or prevent gastrointestinal infections, and microalgae have demonstrated important health-promoting effects and in some cases function as prebiotics. In this regard, the anti-rotavirus effect of Bifidobacterium longum and Chlorella sorokiniana by reducing viral infectivity is well known. However, their effect on immune response against rotavirus has not yet been investigated. Therefore, the aim of this study was to determine the role of Bifidobacterium longum and/or Chlorella sorokiniana in influencing an IFN type I-mediated antiviral response in rotavirus-infected cells. In pre-infection experiments, HT-29 cells were treated with B. longum and C. sorokiniana alone or in combination, followed by rotavirus infection, whereas in post-infection assays, HT-29 cells were treated after infection. The cells' mRNA was then purified to determine the relative expression level of IFN-α, IFN-ß, and precursors of interferons such as RIG-I, IRF-3, and IRF-5 by qPCR. We showed that combination of B. longum and C. sorokiniana significantly increased IFN-α levels in pre-infection and IFN-ß in post-infection assays, as compared with individual effects. Results indicate that B. longum, C. sorokiniana, or their combination improve cellular antiviral immune response.

Gene regulatory network inference in the era of single-cell multi-omics.

The interplay between chromatin, transcription factors and genes generates complex regulatory circuits that can be represented as gene regulatory networks (GRNs). The study of GRNs is useful to understand how cellular identity is established, maintained and disrupted in disease. GRNs can be inferred from experimental data - historically, bulk omics data - and/or from the literature. The advent of single-cell multi-omics technologies has led to the development of novel computational methods that leverage genomic, transcriptomic and chromatin accessibility information to infer GRNs at an unprecedented resolution. Here, we review the key principles of inferring GRNs that encompass transcription factor-gene interactions from transcriptomics and chromatin accessibility data. We focus on the comparison and classification of methods that use single-cell multimodal data. We highlight challenges in GRN inference, in particular with respect to benchmarking, and potential further developments using additional data modalities.

Cytotoxic, Anti-Hemolytic, and Antioxidant Activities of Ruta chalepensis L. (Rutaceae) Extract, Fractions, and Isolated Compounds.

Ruta chalepensis is an herb used to treat various ailments, and its potential cytotoxic effects on different tumor cell lines have been extensively studied. The present study aimed to evaluate the cytotoxic activity of R. chalepensis methanol extract (RCME), sub-partitions obtained from solvents of increasing polarity, and major compounds, as well as their hemolytic, anti-hemolytic, and antioxidant potential. The in vitro cytotoxic activity against the human hepatocarcinoma (HEP-G2) and the murine lymphoma cell line (L5178Y-R) was evaluated using the colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay, whereas selectivity indices (SIs) were determined by comparing cytotoxicity against normal African green monkey kidney cells (VERO) and human peripheral blood mononuclear cells (PBMC). Hemolytic and anti-hemolytic activities were evaluated on human erythrocytes. The most effective cytotoxic treatment was evaluated for nitric oxide release by J774A.1 macrophages. Antioxidant activity of R. chalepensis material was also determined. Results showed that RCME produced significant (p < 0.05) cytotoxicity in HEP-G2 (IC50 = 1.79 µg/mL) and L5178Y-R (IC50 = 1.60 µg/mL) cells and exhibited high SIs (291.50 and 114.80, respectively). In addition, the n-hexane fraction (RCHF) showed an IC50 of 18.31 µg/mL in HEP-G2 cells and an SI of 9.48 in VERO cells, whereas the chloroform fraction (RCCF) evidenced an IC50 of 1.60 µg/mL in L5178Y-R cells and an SI of 34.27 in PBMC cells. Chalepensin (CHL), rutamarin (RTM), and graveolin (GRV), which are major components of R. chalepensis, showed high activity against L5178Y-R cells, with IC50 of 9.15, 15.13 and SI of 45.08 µg/mL, respectively. In addition, CHL, RTM, and GRV showed SIs of 24.76, 9.98, and 3.52, respectively, when compared with PBMC cells. RCME at concentrations of 125 µg/mL and 250 µg/mL, significantly (p < 0.05) decreased nitrite production in J774A.1 cells, when exposed to lipopolysaccharide. This study demonstrated that RCME showed significant cytotoxic activity against HEP-G2 and L5178Y-R cells, without affecting normal VERO, PBMC, and J774A.1 cells.

Evaluation of DNA damage in obese children using the chromatin dispersion test.

Childhood obesity predicts adult obesity and may increase the lifetime risk of adverse health outcomes. Obesity is characterized by oxidative stress that can induce DNA damage; however, studies of childhood and adolescent obesity are scarce. We investigated DNA damage due to obesity in Mexican children using the chromatin dispersion test (CDT). We evaluated DNA damage to peripheral lymphocytes of 32 children grouped according to body mass index as normal weight (controls), overweight and obese groups using guidelines from the Centers for Disease Control (CDC). We found that the greatest DNA damage occurred in cells of obese children compared to normal weight and overweight children. Our findings support preventive action to obviate adverse health outcomes due to obesity.