Long-term exposure changes the environmentally relevant bis(2-ethylhexyl) phthalate to be a neuro-hazardous substance disrupting neural homeostasis in emotional and cognitive functions
Jae Soon Kang, Ji Hyeong Baek, Mi yeong Song, Naveed ur Rehman, Hye Jin Chung, Dong‐Kun Lee, Dae Young Yoo, Hyun Joon Kim
IF 7.3
Environmental Pollution
Bis(2-ethylhexyl) phthalate (DEHP) is the most used member of the phthalate class of compounds. Extensive use of this plasticizer allows daily exposure to humans via various routes. A positive relationship between DEHP exposure and neurobehavioral disorders is suspected. But, there are insufficient data on the harmfulness of neurobehavioral disorders caused by DEHP exposure, particularly at daily exposure levels. In this study, we assessed the consequences of daily DEHP ingestion (2 and 20 mg/kg diets) in male mice for at least 100 days and examined its effects on neuronal functions associated with neurobehavioral disorders, such as depression and cognitive decline. We found the marked depressive behaviors and reduced learning and memory function in the DEHP-ingestion groups, and that biomarkers related to chronic stress were increased in plasma and brain tissues. Long-term DEHP ingestion induced collapse of glutamate (Glu) and glutamine (Gln) homeostasis as a result of disruption of the Glu-Gln cycle in the medial prefrontal cortex and hippocampus. The reduced glutamatergic neurotransmission activity caused by DEHP ingestion was demonstrated using an electrophysiological method. This study revealed that long-term exposure to DEHP is hazardous and can cause neurobehavioral disorders, even at daily exposure levels.
Efficient Stereoselective Synthesis of Vepdegestrant (ARV‐471) via Ruthenium‐Catalyzed Asymmetric Hydrogenation
Neerasa Jayaprakash, Byeonggwan Kim, Hye Jin Chung
IF 2
ChemistrySelect
Abstract Vepdegestrant (ARV‐471) is a novel estrogen receptor (ER) degrader currently under clinical evaluation for the treatment of ER‐positive and HER2‐negative breast cancer. We have developed an efficient catalytic stereoselective synthetic route to produce this important compound. The key step involves a Ruthenium‐catalyzed asymmetric hydrogenation, which establishes the critical stereocenter with exceptional diastereoselectivity(>99% de). This method obviates the need for chiral chromatographic separation, thereby significantly improving the efficiency and scalability of the synthetic sequence compared to previously reported approaches.
Expectorant Effects of Atractylodes japonica Koidz. ex Kitam Root Extracts on Particulate Matter-Induced Pulmonary Injury in Mice
Jin Ho Lee, Sana Mansoor, Jeongjun Lee, Hye Jin Chung, Young-Sam Kwon, Khawaja Muhammad Imran Bashir, Jae‐Suk Choi, Sae‐Kwang Ku
IF 2.5
Applied Sciences
This study investigated the growing environmental concern of particulate matter (PM)-induced pulmonary injury and explored novel preventive strategies. In particular, it evaluated the protective effects of Atractylodes japonica Koidz. ex. Kitam root extract (AJ), which is known for its anti-inflammatory and antioxidant properties, against PM2.5-induced subacute pulmonary injuries in Balb/c mice. The experimental design involved administering AJ at a concentration from 400 to 100 mg/kg over a ten-day period, with comparisons made to the mucolytic agent ambroxol hydrochloride (AX). The results revealed that AJ significantly alleviated PM2.5-induced pulmonary injuries, mucus overproduction, and respiratory acidosis in a dose-dependent manner. Notably, body surface redness was reduced by up to 55% at a concentration of 100 mg/kg compared to the control. These effects were evidenced by reduced mRNA expression of the mucus-associated genes MUC5B and MUC5AC and increased concentrations of substance P (up to 475%) and acetylcholine (up to 355%) in the lungs at 400 mg/kg, compared to the intact vehicle control. Particularly, the 400 mg/kg dose of AJ demonstrated comparable effectiveness to AX, highlighting its potent mucolytic and expectorant activities. The results of this study highlight the fact that AJ could act as a promising alternative for respiratory protection, with potential applications as a functional food ingredient. This study substantiates AJ’s role in enhancing respiratory health, emphasizing its capacity as a candidate for further development into therapeutic agents against toxic environmental exposure.
The Korean Society for the Study of Moral Education
The moral law and the idea of freedom are the core concepts of Kant’s ethics. Through consideration of this concept, this study revealed what Kant has done in the field of ethics. Kant revealed that there is ‘the cause of freedom’ in humans, and that the cause of freedom is a ‘logical cause’ in that it is a regulation in the practical aspect of ‘pure reason’. What Kant did in the first critique revealed that human cognitive behavior contains ‘pure reason’ as an a priori condition of perception that is not explained only by sensory experience, revealing the metaphysics in epistemology. What Kant did in ethics was reveal that it is none other than metaphysics as a ‘practical use of pure reason’ that enables human moral behavior by revealing the idea of freedom as the basis for the establishment of moral behavior. Based on this, this study examined the characteristics of the second critique seen in relation to the first criticism. Given that the first critique is Kant’s metaphysics, which deals with the outline and fundamentals of the entire system of Kant’s philosophy, and the second critique is Kant’s moral philosophy, which deals with Kant’s ethical criticism in earnest based on the first critique it was discussed that the two critique are related to the metaphysical foundation of Kant’s ehics and that they are also related to epistemology and ethics and metaphysics. Furthermore, this discussion also revealed that its justification can only be secured from a metapraxis perspective (from the perspective of heart cultivation).
Long-term exposure of bis(2-ethylhexyl) phthalate causes neurobehavioral disorders by disrupting glutamate-glutamine homeostasis in the mPFC
Jae Soon Kang, Ji Hyeong Baek, Mi yeong Song, Hyeong Chan Park, Naveed ur Rehman, Hye Jin Chung, Dong‐Kun Lee, Dae Young Yoo, Hyun Joon Kim
ISEE Conference Abstracts
BACKGROUND AND AIM: Bis(2-ethylhexyl) phthalate (DEHP) is the most used phthalate and its extensive use allows daily exposure to humans via various routes. Although a positive relationship between DEHP exposure and neurobehavioral disorders is suspected, there are insufficient data on the harmfulness of neurobehavioral disorders caused by DEHP exposure, particularly at daily exposure levels. We try to identify the relationship between DEHP and neurobehavioral disorders, and explain the underlying mechanism. METHOD: We assessed the consequences of DEHP ingestion including daily exposure concentration in male mice for 30 (short-term) and 100 (long-term) days and examined its effects on neuronal functions associated with neurobehavioral disorders, such as depression and cognitive decline. RESULTS: We found the noticeable depressive behaviors and decline of learning and memory function in the DEHP-ingestion groups, and that biomarkers related to chronic stress such as corticosterone and ROS/RNS were elevated in plasma and brain tissues. DEHP ingestion induced collapse of glutamate (Glu) and glutamine (Gln) homeostasis as a result of disruption of the Glu-Gln cycle in the medial prefrontal cortex and hippocampus. The electrophysiological approach demonstrated that DEHP ingestion lowered the glutamatergic neurotransmission activity involved in emotional and cognitive functions in the brain. CONCLUSIONS: Our research revealed that the long-term exposure of environment-relevant DEHP, even levels of exposure lower than the tolerable daily intake (TDI), have the strong potential to cause neurobehavioral disorders. Further, since the developing and commercializing a safe substance to replace DEHP is a time-consuming process, it is necessary to prepare stricter regulations and to develop and implement a method to prevent neurobehavioral disorders caused by daily exposure to DEHP to protect the human mental health from this hazardous material. This research was supported by the National Research Foundation (NRF-2020R1I1A1A0107229813, 2021R1A5A802949012, 2022R1A2C100529611 and 2023R1A2C1005658) and the Commercializations Promotion Agency for R&D Outcomes (1711173796) funded by the Korea government.
Long-term exposure changes the environmentally relevant bis(2-ethylhexyl) phthalate to be a neuro-hazardous substance disrupting neural homeostasis in emotional and cognitive functions
Jae Soon Kang, Ji Hyeong Baek, Mi yeong Song, Naveed ur Rehman, Hye Jin Chung, Dong‐Kun Lee, Dae Young Yoo, Hyun Joon Kim
IF 7.3
Environmental Pollution
Bis(2-ethylhexyl) phthalate (DEHP) is the most used member of the phthalate class of compounds. Extensive use of this plasticizer allows daily exposure to humans via various routes. A positive relationship between DEHP exposure and neurobehavioral disorders is suspected. But, there are insufficient data on the harmfulness of neurobehavioral disorders caused by DEHP exposure, particularly at daily exposure levels. In this study, we assessed the consequences of daily DEHP ingestion (2 and 20 mg/kg diets) in male mice for at least 100 days and examined its effects on neuronal functions associated with neurobehavioral disorders, such as depression and cognitive decline. We found the marked depressive behaviors and reduced learning and memory function in the DEHP-ingestion groups, and that biomarkers related to chronic stress were increased in plasma and brain tissues. Long-term DEHP ingestion induced collapse of glutamate (Glu) and glutamine (Gln) homeostasis as a result of disruption of the Glu-Gln cycle in the medial prefrontal cortex and hippocampus. The reduced glutamatergic neurotransmission activity caused by DEHP ingestion was demonstrated using an electrophysiological method. This study revealed that long-term exposure to DEHP is hazardous and can cause neurobehavioral disorders, even at daily exposure levels.
