Regulatory science

Exposure to hexavalent chromium damages genetic materials like DNA and chromosomes, further elevating cancer risk, yet research rarely focuses on related immunological mechanisms, which play an important role in the occurrence and development of cancer. We investigated the association between blood chromium (Cr) levels and genetic damage biomarkers as well as the immune regulatory mechanism involved, such as costimulatory molecules, in 120 workers exposed to chromates. Higher blood Cr levels were linearly correlated with higher genetic damage, reflected by urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and blood micronucleus frequency (MNF)...

As the importance of utilizing real-world data (RWD)/real-world evidence (RWE) for supporting regulatory scientific decision-making continues to grow, experiences and inputs from experts become crucial for developing a systematic and practice-oriented plan for the use of fit-for-purpose RWD/RWE. This study aimed to survey relevant experts from government agencies, industries, and academia to identify prerequisites for the drug life cycle in Korea. The questionnaire comprised the following: (A) the definition and categories of RWD/RWE, (B) the suitability and feasibility of using RWD/RWE at each authorization stage by the types of RWD, and (C) the challenges and solutions for the use of RWD/RWE...

Mycotoxins, ubiquitous contaminants in food, present a global threat to human health and well-being. Mitigation efforts, such as the implementation of sound agricultural practices, thorough food processing, and the advancement of mycotoxin control technologies, have been instrumental in reducing mycotoxin exposure and associated toxicity. To comprehensively assess mycotoxins and their toxicodynamic implications, the deployment of effective and predictive strategies is imperative. Understanding the manner of action, transformation, and cumulative toxic effects of mycotoxins, moreover, their interactions with food matrices can be gleaned through gene expression and transcriptome analyses at cellular and molecular levels...

PURPOSE: The first paper to specify the core content of pharmacoepidemiology as a profession was published by an ISPE (International Society for Pharmacoepidemiology) workgroup in 2012 (Jones JK et al. PDS 2012; 21[7]:677-689). Due to the broader and evolving scope of pharmacoepidemiology, ISPE considers it important to proactively identify, update and expand the list of core competencies to inform curricula of education programs; thus, better positioning pharmacoepidemiologists across academic, government (including regulatory), and industry positions...

OBJECTIVES: Skeletal muscles mitochondrial dysfunction is the main cause of sarcopenia. Both electroacupuncture (EA) and sulforaphane (SFN) have been shown to improve oxidative stress and inflammation levels to maintain mitochondrial function, but the effects and mechanisms of their combination on sarcopenia are unclear. This study aimed to investigate the regulatory effects of EA combined with SFN on sarcopenia. MATERIALS AND METHODS: SAMP8 mice were used and intervened with EA or SFN, respectively, and Masson and HE staining were used to observe pathological changes in skeletal muscle tissue...

Metabolic syndrome (MetS) is a cluster of metabolic abnormalities that has a high prevalence worldwide. Apigenin is a flavonoid present in several vegetables and fruits and has anti-inflammatory, anti-oxidant, and anti-MetS properties. This study aims to systematically review the effects of apigenin against MetS and the relevant molecular and cellular mechanisms of action, pharmacokinetics features, and potential structure-activity relationship. Electronic databases including Scopus, PubMed, Science Direct and Cochrane Library were searched for in vivo, and in vitro, and human studies with the following keywords: "apigenin" and "metabolic syndrome or insulin resistance syndrome", "fatty liver", "hypertension or blood pressure", "diabetes or blood glucose", "dyslipidemia", "heart or cardiovascular " and "obesity" in title/abstract...

The strategies that enable musicians to adapt their behaviors so that they can break through, feel energized, and perform well collectively distinguish what it is to be a self-regulated learner. These strategies range from one's ability to monitor thoughts and actions to being able to navigate and control one's emotions, especially when feeling frustrated or anxious. Given the challenges of the music profession, it becomes imperative for teachers to equip their students with the necessary skills to self-regulate their own actions, feelings, and thinking so that they are eventually able to cope with the demands required of a contemporary professional musical career...

The RNA modification 5-methylcytosine (m5C) is widespread across various RNA types, significantly impacting RNA stability and translational efficiency. Accumulating evidence highlights its significant role within the tumorigenesis and progression of multiple malignancies. Nevertheless, the specific process through m5C is implicated in Glioblastoma (GBM) remains unclear. We conducted acomprehensive analysis of m5C expression distribution in single-cell GBM data. Our findings revealed elevated m5C scores in GBM single-cell data compared to the normal group...

BACKGROUND: Uterine corpus endometrial cancer (UCEC) exhibit heterogeneity in their DNA repair capacity, which can impact their response to radiotherapy. Our study aimed to identify potential DNA repair-related biomarkers for predicting radiation response in UCEC. METHODS: We conducted a thorough analysis of 497 UCEC samples obtained from TCGA database. Using LASSO-COX regression analysis, we constructed a radiosensitivity signature and subsequently divided patients into the radiosensitive (RS) and the radioresistant (RR) groups based on their radiosensitivity index...

Despite extensive research reveal rheumatoid arthritis (RA) is related to atherosclerosis (AS), common pathogenesis between these two diseases still needs to be explored. In current study, we explored the common pathogenesis between rheumatoid arthritis (RA) and atherosclerosis (AS) by identifying 297 Differentially Expressed Genes (DEGs) associated with both diseases. Through KEGG and GO functional analysis, we highlighted the correlation of these DEGs with crucial biological processes such as the vesicle transport, immune system process, signaling receptor binding, chemokine signaling and many others...

OBJECTIVES: The impact of N7-methylguanosine (m7G) on tumor progression and the regulatory role of microRNAs (miRNAs) in immune function significantly influence breast cancer (BC) prognosis. Investigating the interplay between m7G modification and miRNAs provides novel insights for assessing prognostics and drug responses in BC. MATERIALS AND METHODS: RNA sequences (miRNA and mRNA profiles) and clinical data for BC were acquired from the Cancer Genome Atlas (TCGA) database...

Genetic diseases are currently diagnosed by functional mutations. However, only some mutations are associated with disease. It is necessary to establish a quick prediction model for clinical screening. Pathogenic mutations in NGLY1 cause a rare autosomal recessive disease known as congenital disorder of deglycosylation (NGLY1-CDDG). Although NGLY1-CDDG can be diagnosed through gene sequencing, clinical relevance of a detected mutation in NGLY1 needs to be further confirmed. In this study, taken NGLY1-CDDG as an example, a comprehensive and practical predictive model for pathogenic mutations on NGLY1 through an NGLY1/Glycopeptide complex model was constructed, the binding sites of NGLY1 and glycopeptides were simulated, and an in vitro enzymatic assay system was established to facilitate quick clinical decisions for NGLY1-CDDG patients...

Stomata play a pivotal role in balancing CO2 uptake for photosynthesis and water loss via transpiration. Thus, appropriate regulation of stomatal movement and its formation are crucial for plant growth and survival. Red and blue light induce phosphorylation of the C-terminal residue of the plasma membrane (PM) H+ -ATPase, threonine, in guard cells, generating the driving force for stomatal opening. While significant progress has been made in understanding the regulatory mechanism of PM H+ -ATPase in guard cells, the regulatory components for the phosphorylation of PM H+ -ATPase have not been fully elucidated...

Among the bioactive compounds, lipid-soluble tanshinone is present in Salvia miltiorrhiza , a medicinal plant species. While it is known that ethephon has the ability to inhibit the tanshinones biosynthesis in the S. miltiorrhiza hairy root, however the underlying regulatory mechanism remains obscure. In this study, using the transcriptome dataset of the S. miltiorrhiza hairy root induced by ethephon, an ethylene-responsive transcriptional factor EIN3-like 1 ( SmEIL1 ) was identified. The SmEIL1 protein was found to be localized in the nuclei, and confirmed by the transient transformation observed in tobacco leaves...

Oregano ( Origanum vulgare ) seed is used as spices and is known to have anti-inflammatory, antibacterial, and antioxidant effects. The anti-fatty liver effects of oregano seed ethyl acetate (OSEA) were evaluated in high-fat diet (HFD)-induced obese mice. OSEA was orally administered with HFD for 10 weeks. The body weight, aspartate aminotransferase, alanine aminotransferase, cholesterol, triglyceride, and low-density lipoprotein levels in the HFD with 100 mg/kg of OSEA significantly decreased by approximately 1...

Imagine consuming a daily diet rich in fatty acids to help treat diseases such as hypertension and obesity. This concept presents an attractive paradox. In particular, consuming walnut kernels is beneficial for treating diseases associated with metabolic syndrome (MetS), including type 2 diabetes, cardiovascular disease, dyslipidemia, and obesity. Different parts of the Juglans regia tree (family Juglandaceae), including its leaves, green husks, bark, and septum, have shown promising effects on pathological conditions related to MetS...

Resveratrol, a natural polyphenol in various plants, has gained significant attention for its potential health-promoting properties. It has been demonstrated, after reviewing various clinical and in vitro studies, that resveratrol possesses potent antioxidant potential. Resveratrol demonstrates cellular component protection by directly neutralizing free radicals (FRs) and enhancing the expression of natural antioxidant enzymes, thereby mitigating oxidative damage to proteins, lipids, and nucleic acids...

BACKGROUND: Stress is a recognized risk factor for cognitive decline, which triggers neuroinflammation involving microglial activation. However, the specific mechanism for microglial activation under stress and affects learning and memory remains unclear. METHODS: The chronic stress mouse model was utilized to explore the relationship between microglial activation and spatial memory impairment. The effect of hippocampal hyperglycemia on microglial activation was evaluated through hippocampal glucose-infusion and the incubation of BV2 cells with high glucose...

BACKGROUND: Although the importance of context in implementation science is not disputed, knowledge about the actual impact of external context variables on implementation processes remains rather fragmented. Current frameworks, models, and studies merely describe macro-level barriers and facilitators, without acknowledging their dynamic character and how they impact and steer implementation. Including organizational theories in implementation frameworks could be a way of tackling this problem...

Cytosolic Ca2+ and Na+ allosterically regulate Na+ /Ca2+ exchanger (NCX) proteins to vary the NCX-mediated Ca2+ entry/exit rates in diverse cell types. To resolve the structure-based dynamic mechanisms underlying the ion-dependent allosteric regulation in mammalian NCXs, we analyze the apo, Ca2+ , and Na+ -bound species of the brain NCX1.4 variant using hydrogen-deuterium exchange mass spectrometry (HDX-MS) and molecular dynamics (MD) simulations. Ca2+ binding to the cytosolic regulatory domains (CBD1 and CBD2) rigidifies the intracellular regulatory loop (5L6) and promotes its interaction with the membrane domains...