Selective Interactions of Valeriana officinalis Extracts and Valerenic Acid with [3H]Glutamate Binding to Rat Synaptic Membranes

Although GABA neurotransmission has been suggested as a mechanism for Valeriana officinalis effects, CNS depression can also be evoked by inhibition of ionotropic (iGluR) and metabotropic glutamate receptors (mGluR). In this study, we examined if aqueous valerian extract interacted with glutamatergic receptors. Freshly prepared aqueous valerian extract was incubated with rat cortical synaptic membranes in presence of 20 nM [3H]Glutamate. Aqueous valerian extract increased [3H]Glutamate binding from 1 × 10−7 to 1 × 10−3 mg/mL. In the presence of (2S,1′S,2′S)-2-(Carboxycyclopropyl)glycine (LCCG-I) and (2S,2′R,3′R)-2-(2′,3′-Dicarboxycyclopropyl)glycine (DCG-IV), Group II mGluR agents, valerian extract markedly decreased [3H]Glutamate binding, while (2S)-2-amino-3-(3,5-dioxo-1,2,4-oxadiazolidin-2-yl) propanoic acid) (quisqualic acid, QA), Group I mGluR agonist, increased [3H]Glutamate binding. At 0.05 mg/mL aqueous valerian extract specifically interacted with kainic acid NMDA and AMPA receptors. Valerenic acid, a marker compound for Valeriana officinalis, increased the [3H]Glutamate binding after 1.6 × 10−2 mg/mL, and at 0.008 mg/mL it interacted only with QA (Group I mGluR). The selective interactions of valerian extract and valerenic acid with Group I and Group II mGluR may represent an alternative explanation for the anxiolytic properties of this plant

A Role for MEK3 in the Oncogenesis of Acute Lymphocytic Leukemia: Inactivation of MAPK P38 Promotes Cell Proliferation Through Enhanced Degradation of Mutant MEK3

In the United States, pediatric leukemia has the second-highest cancer mortality rate in Hispanic children, especially Acute Lymphocytic Leukemia (ALL). While treatment of ALL has improved overall the five-year survival rate of ~90 %, not everyone has benefited. Twenty percent of them will experience relapse, and from these, 30 – 50 % will die. Unfortunately, the cause behind these dreadful statistics is poorly understood due to the complex etiology of this disease. Thereby, it is essential to identify potential oncogenic proteins that promote ALL so that new strategies can be developed to diagnose and treat this cancer. Whole Exome Sequencing (WES) coupled with OncoMiner Pipeline sorting identified five Single Nucleotide Polymorphisms (SNP’s) on the Mitogen-Activated Protein Kinase Kinase 3 (MEK3) (MAP2K3) gene in El Paso del Norte ALL cancer patient library. MAP2K3 mutations were recreated using site-directed mutagenesis and transfected into HEK293 cells to study their impact on cell function. Three mutations were located within the kinase domain and two others located to the MEK3 amino domain. Transfection of HEK293 cells revealed these variants impact protein stability by inducing increased degradation of MEK3. Data shown here further suggest that they serve to block the auto-phosphorylation of MEK3, and loss of kinase activity towards p38. MEK3 is responsible for the activation of MAPK p38 to mediate growth-inhibitory and pro-apoptotic signals. Thus, inhibition of p38 activity through enhanced degradation of MEK3 mutants renders this pathway nonfunctional contributing to tumor cell proliferation. These findings indicate MEK3 represents a therapeutic target for controlling and treating ALL

Toward Language Justice in Environmental Health Sciences in the United States: A Case for Spanish as a Language of Science

BackgroundIncreasingly, marginalized communities are disproportionately facing the worsening effects of environmental hazards, including air pollution, water pollution, and climate change. Language isolation and accessibility has been understudied as a determinant of health. Spanish, despite being the second-most common language in the United States with some 41.8 million speakers, has been neglected among environmental health scientists. Building capacity in high-quality Spanish-language science communication, both for scientific and nonscientific audiences, can yield improvements in health disparities research, public health literacy, international collaborations, and diversity and inclusion efforts.ObjectivesIn this article, we discuss the context of language diversity in environmental health sciences and offer recommendations for improving science communication in Spanish.DiscussionEnglish is currently the predominant language for scientific discourse, but Spanish and other non-English languages are routinely used by many environmental health science students and professionals, as well as much of the public. To more effectively conduct and communicate environmental health work in Spanish, we suggest that researchers and scientific institutions a) foster structural changes, b) train emerging scholars and support established researchers, c) tap into community ways of knowing, and d) leverage emerging technologies. https://doi.org/10.1289/EHP12306

Perceptions and experiences of environmental health and risks among Latina mothers in urban Los Angeles, California, USA

Abstract Background Environmental exposures during pregnancy and early childhood can have acute and chronic adverse health impacts. As minoritized populations are more likely to reside in areas with greater pollution, it is important to understand their views and lived experiences to inform action. The purpose of this community-driven qualitative research study was to understand how urban Latina mothers in Los Angeles County, California perceived environmental health and risks. Methods We conducted semi-structured individual interviews with Latina pregnant women and mothers of young children, recruited through existing collaborations with community organizations. Interviews conducted in either English or Spanish and were coded inductively according to a modified grounded theory approach. Results Thirty-six Latina mothers completed interviews between August–October 2016. Participants lived primarily in low-income communities of South-Central Los Angeles and East Los Angeles. We identified three major themes based on the participants’ responses during interviews: Defining the Environment, Environment & Health Risks, and Social & Political Responsibility. Women defined their environment in terms of both “nature” and “hazards.” They consistently identified foul odors, dirtiness, noise, trash, bugs, smoke, and other visible blights as indicators of household and neighborhood environmental hazards. They expressed fear and uncertainty about how their environment could affect their health and that of their children, as well as specific concerns about respiratory health, asthma, allergies, cancer, and adverse pregnancy outcomes. Mothers often changed individual behaviors around diet and cleaning during pregnancy but were frustrated by power imbalances that left them unable to change their home or neighborhood environments, despite their desire to do so. Discussion Our study is among the first to describe how urban Latina mothers perceive and experience environmental health risks during pregnancy and early childhood. Our research suggests additional attention is needed by public health professionals and researchers to address the environmental health risks that matter most to urban Latina mothers. They also highlight the tension that many urban Latina mothers feel between wanting to protect their families’ health and well-being and feeling powerless to change their environment. Broad policy changes, rather than additional individual recommendations, are needed to address the concerns of this vulnerable population

Depressed contractile function due to canine mitral regurgitation improves after correction of the volume overload.

It is known that long-standing volume overload on the left ventricle due to mitral regurgitation eventually leads to contractile dysfunction. However, it is unknown whether or not correction of the volume overload can lead to recovery of contractility. In this study we tested the hypothesis that depressed contractile function due to volume overload in mitral regurgitation could return toward normal after mitral valve replacement. Using a canine model of mitral regurgitation which is known to produce contractile dysfunction, we examined contractile function longitudinally in seven dogs at baseline, after 3 mo of mitral regurgitation, 1 mo after mitral valve replacement, and 3 mo after mitral valve replacement. After 3 mo of mitral regurgitation (regurgitant fraction 0.62 +/- 0.04), end-diastolic volume had nearly doubled from 68 +/- 6.8 to 123 +/- 12.1 ml (P less than 0.05). All five indices of contractile function which we examined were depressed. For instance, maximum fiber elastance (EmaxF) obtained by assessment of time-varying elastance decreased from 5.95 +/- 0.71 to 2.25 +/- 0.18 (P less than 0.05). The end-systolic stiffness constant (k) was also depressed from 4.2 +/- 0.4 to 2.1 +/- 0.3. 3 mo after mitral valve replacement all indexes of contractile function had returned to or toward normal (e.g., EmaxF 3.65 +/- 0.21 and k 4.2 +/- 0.3). We conclude that previously depressed contractile function due to volume overload can improve after correction of the overload