Evaluating Novel SP-B and SP-C Synthetic Analogues for Pulmonary Surfactant Efficacy.

Pulmonary surfactants, a complex assembly of phospholipids and surfactant proteins such as SP-B and SP-C, are critical for maintaining respiratory system functionality by lowering surface tension (ST) and preventing alveolar collapse. Our study introduced five synthetic SP-B peptides and one SP-C peptide, leading to the synthesis of CHAsurf candidates (CHAsurf-1 to CHAsurf-5) for evaluation. We utilized a modified Wilhelmy balance test to assess the surface tension properties of the surfactants, measuring spreading rate, surface adsorption, and ST-area diagrams to comprehensively evaluate their performance. Animal experiments were performed on New Zealand white rabbits to test the efficacy of CHAsurf-4B, a variant chosen for its economic viability and promising ST reduction properties, comparable to Curosurf®. The study confirmed that higher doses of SP-B in CHAsurf-4 are associated with improved ST reduction. However, due to cost constraints, CHAsurf-4B was selected for in vivo assessment. The animal model revealed that CHAsurf-4B could restore alveolar structure and improve lung elasticity, akin to Curosurf®. Our research highlights the significance of cysteine residues and disulfide bonds in the structural integrity and function of synthetic SP-B analogues, offering a foundation for future surfactant therapy in respiratory disorders. This study's findings support the potential of CHAsurf-4B as a therapeutic agent, meriting further investigation to solidify its role in clinical applications.

Artificial Intelligence-Driven Respiratory Distress Syndrome Prediction for Very Low Birth Weight Infants: Korean Multicenter Prospective Cohort Study.

BACKGROUND: Respiratory distress syndrome (RDS) is a disease that commonly affects premature infants whose lungs are not fully developed. RDS results from a lack of surfactant in the lungs. The more premature the infant is, the greater is the likelihood of having RDS. However, even though not all premature infants have RDS, preemptive treatment with artificial pulmonary surfactant is administered in most cases. OBJECTIVE: We aimed to develop an artificial intelligence model to predict RDS in premature infants to avoid unnecessary treatment. METHODS: In this study, 13,087 very low birth weight infants who were newborns weighing less than 1500 grams were assessed in 76 hospitals of the Korean Neonatal Network. To predict RDS in very low birth weight infants, we used basic infant information, maternity history, pregnancy/birth process, family history, resuscitation procedure, and test results at birth such as blood gas analysis and Apgar score. The prediction performances of 7 different machine learning models were compared, and a 5-layer deep neural network was proposed in order to enhance the prediction performance from the selected features. An ensemble approach combining multiple models from the 5-fold cross-validation was subsequently developed. RESULTS: Our proposed ensemble 5-layer deep neural network consisting of the top 20 features provided high sensitivity (83.03%), specificity (87.50%), accuracy (84.07%), balanced accuracy (85.26%), and area under the curve (0.9187). Based on the model that we developed, a public web application that enables easy access for the prediction of RDS in premature infants was deployed. CONCLUSIONS: Our artificial intelligence model may be useful for preparations for neonatal resuscitation, particularly in cases involving the delivery of very low birth weight infants, as it can aid in predicting the likelihood of RDS and inform decisions regarding the administration of surfactant.

Birth Rate Transition in the Republic of Korea: Trends and Prospects.

BACKGROUND: In Korea, the birth rate is declining at an alarming pace. This study aimed to investigate the changes and trends in the population count, number of births, and birth rate in Korea, in the past and future. METHODS: Data regarding the total number of births, crude birth rate, and total fertility rate were collected from the "Statistics Korea Census" of the national statistical portal, census report, and Statistics Korea's "2020 Population Trend Survey for 1981-2020, provisional results of birth and death statistics." We used the Organisation for Economic Co-operation and Development 2019 Family Database for the TFR. To develop a better understanding of the data in this study, we classified it according to the modern history of Korea. RESULTS: The changes and trends in the number of births and fertility rate in Korea, after liberation, were due to the birth control policy that restricted births. In Korea's low fertility society, which began in the mid-2000s, the fertility rate dropped to below 0.84 in 2020, despite policies to improve the quality of the population. The death toll has reached 300,000, entering an era of population decline. CONCLUSION: As we enter the era of population decline, we are in a direction that will cause various socioeconomic problems, from demographic problems to future population decline.

Survey on the Status of Breastfeeding in Korean Medical Institution Workers.

BACKGROUND: Human breast milk is essential and provides irreplaceable nutrients for early humans. However, breastfeeding is not easy for various reasons in medical institution environments. Therefore, in order to improve the breastfeeding environment, we investigated the difficult reality of breastfeeding through questionnaire responses from medical institution workers. METHODS: A survey was conducted among 179 medical institution workers with experience in childbirth within the last five years. The survey results of 175 people were analyzed, with incoherent answers excluded. RESULTS: Of the 175 people surveyed, a total of 108 people (61.7%) worked during the day, and 33 people (18.9%) worked in three shifts. Among 133 mothers who stayed with their babies in the same nursing room, 111 (93.3%) kept breastfeeding for more than a month, but among those who stayed apart, only 10 (71.4%) continued breastfeeding for more than a month (P = 0.024). Ninety-five (88.0%) of daytime workers, 32 (94.1%) two-shift workers, and 33 (100%) three-shift workers continued breastfeeding for more than a month (P = 0.026). Workers in general hospitals tended to breastfeed for significantly longer than those that worked in tertiary hospitals (P = 0.003). A difference was also noted between occupation categories (P = 0.019), but a more significant difference was found in the comparison between nurses and doctors (P = 0.012). Longer breastfeeding periods were noted when mothers worked three shifts (P = 0.037). Depending on the period planned for breastfeeding prior to childbirth, the actual breastfeeding maintenance period after birth showed a significant difference (P = 0.002). Of 112 mothers who responded to the question regarding difficulties in breastfeeding after returning to work, 87 (77.7%) mentioned a lack of time caused by being busy at work, 82 (73.2%) mentioned the need for places and appropriate circumstances. CONCLUSION: In medical institutions, it is recommended that environmental improvements in medical institutions, the implementation of supporting policies, and the provision of specialized education on breastfeeding are necessary to promote breastfeeding.

Seon Master Daehaeng and William James on Religious Faith.

In this essay, I attempt to critically visit the psychology of religion movement along with hanmaum studies, focusing on their respective founders, William James (1842-1910) and Seon Master Daehaeng (1927-2012). Both founders emphasized the importance of having a religious faith dimension in our human lives. I focus on describing how their emphasis on the importance of faith is to be related to their experience of life. It should be remembered that they did not actively speculate on matters of faith but preferred, in an empirical way, to work with their concrete experience. Furthermore, for an in-depth study of their fundamental perspectives, I try to articulate what existed as their common ultimate reference point, even if differently named and framed-the "something more" described by James and the Juingong discussed by Daehaeng.

Antenatal Betamethasone Induces Increased Surfactant Proteins and Decreased Foxm1 Expressions in Fetal Rabbit Pups.

Introduction: Antenatal steroid improves respiratory distress syndrome in preterm infants. The molecular mechanism of the process is not well established. The aim of this study is to investigate the possible association between antenatal steroid and fetal Forkhead box M1(Foxm1) expression. Materials and methods: An animal study using mated pregnant New Zealand white rabbits and their fetuses was designed. Fourteen mother rabbits were assigned to four groups to undergo a cesarean section. In groups 1, 2, and 3, preterm pups were harvested on day 27 of gestation. In group 4, term pups were harvested on day 31. Antenatal maternal intramuscular injection was performed in groups 2 (normal saline) and 3 (betamethasone). Using qRT-PCR and Western blot, mRNA transcription and protein expression of surfactant protein (SP) A, B, C, and Foxm1 were compared between the pups of those four groups. Results: Sixty two fetal rabbits were harvested. One-way ANOVA test showed higher mRNA transcription of SPs in groups 3 and 4 than groups 1 and 2. Significantly lower Foxm1 mRNA transcription and protein expression were observed in group 3 or 4 compared with group 1 or 2. Conclusion: Decreased Foxm1 expression was associated in an antenatal betamethasone animal model.

Challenges of acute peritoneal dialysis in extremely-low-birth-weight infants: a retrospective cohort study.

BACKGROUND: Peritoneal dialysis (PD) has been used occasionally in extremely-low-birth-weight (ELBW) infants with acute kidney injury (AKI). This study aimed to evaluate the clinical characteristics and outcomes of ELBW infants with AKI treated with PD. METHODS: In this retrospective cohort study, the medical records of ELBW infants with AKI, who underwent PD from January 2008 to February 2018, were reviewed. A PD catheter (7.5-9.0 Fr) or central venous catheter (4 Fr) was used for the peritoneal access. Treatment with PD solutions (2.5 or 4.25%) was started at 10 mL/kg, which was increased to 20-30 mL/kg for 60-120 min/cycle continuing for 24 h. RESULTS: Twelve ELBW infants (seven male and five female infants) were treated, and their mean (±SD) gestational age and birth weight were 27.2 (±3.3) weeks and 706.5 (±220.5) g, respectively. Two patients had severe perinatal asphyxia (5-min Apgar score ≤ 3). The most important indication for starting PD was AKI due to sepsis. The average (±SD) duration of PD was 9.4 (± 7.7) days. The potassium levels in the ELBW infants with hyperkalemia decreased from 6.8 to 5.0 mg/mL after 9.3 (± 4.4) days. The most common complication of PD was mechanical dysfunction of the catheters, such as dialysate leakage (75%). Two patients were successful weaned off PD. The mortality rate of the infants treated with PD was 91.7%. CONCLUSIONS: In this series, the mortality rate of ELBW infants with AKI treated with PD was relatively high because of their incompletely developed organ systems. Therefore, the use of PD should be carefully considered for the treatment of ELBW infants with AKI in terms of decisions regarding resuscitation.

Decoding neuropathic pain severity using distinct patterns of corticolimbic metabotropic glutamate receptor 5.

Susceptibility to neuropathic pain and the degree of pain amplification vary among individuals. However, methods for objective evaluation of pain status have not been well established. Using an animal model, we identified the brain signature of neuropathic pain, and developed a method for the objective evaluation of pain degree. We analyzed paw withdrawal thresholds from rats that were subjected to right L5 spinal nerve ligation (SNL) surgery, and regressed them to the metabotropic glutamate receptor 5 (mGluR5) availability levels in the brain using [11C] ABP688 PET image data from our previous research. We found clusters with a significant correlation to paw withdrawal threshold localized in brain areas involved in sensory, cognitive, and affective aspects of pain processing. Strikingly, mGluR5 availability levels in the identified brain regions showed distinct patterns in the neuropathic pain group but not in the control group. We successfully elucidated the degree of pain-sensing behavior using the neuropathic pain-specific pattern of the mGluR5 availability. Our study provides new insight into the signature of neuropathic pain in the brain, and offers a novel diagnostic method for objectively decoding the status of individual neuropathic pain.

Parthenolide, a feverfew-derived phytochemical, ameliorates obesity and obesity-induced inflammatory responses via the Nrf2/Keap1 pathway.

Parthenolide (PL) is one of the most abundant sesquiterpene lactones found in the plant feverfew (Tanacetum parthenium (L.) Sch.Bip.). PL was investigated for its effect on obesity and obesity-induced inflammatory/oxidant responses in vitro and in vivo. An obesity-induced inflammatory response was induced in various co-culture systems using adipocytes (3T3-L1) and macrophages (RAW264.7) in vitro and the effect of PL and its mechanism of action were determined. PL effectively suppressed the adiposity-induced inflammatory responses by downregulating IL-6 (40-42%) and MCP-1 (26-37%) in 3T3-CM-cultured macrophages and contact co-culture system. PL also favorably regulated the dysregulations of adiponectin and resistin in macrophage-conditioned medium (RAW-CM)-cultured adipocytes. In transwell system of adipocyte and macrophage, PL was shown to upregulated Nrf2 and its target molecule, HO-1 by promoting nuclear translocation of Nrf2. In particular, in siRNA knockdown study, the PL-mediated anti-inflammatory response was exerted via the Nrf2/Keap1 pathway. In animal study using high-fat diet (HFD)-fed mice, PL-administered mice showed a significant reduction in body weight and white adipose tissues (WATs). This PL-mediated anti-obese effect was connected to anti-inflammatory responses with the regulation of inflammatory cytokines, and the downregulation of NF-κB and MAPKs. Furthermore, PL differentially modulated CD11c and CD206, which are pro-/anti-inflammatory phenotypes of ATMs, in stroma vascular fraction (SVF) and immunohistochemistry (IHC) staining analyses. PL also regulated the level of (anti)oxidant molecules with the activation of Nrf2/Keap1signaling. Taken together, PL inhibited obesity and obesity-induced inflammatory responses via the activation of Nrf2/Keap1 signaling, indicating a potential of PL as a functional agent to control obesity-related diseases.

History of Pulmonary Surfactant Replacement Therapy for Neonatal Respiratory Distress Syndrome in Korea.

Neonatal respiratory distress syndrome (RDS) is a disease that is unique to newborn infants. It is caused by a deficiency of pulmonary surfactant (PS), which is usually ready to be activated around the perinatal period. Until RDS was more clearly understood, it was not known why premature infants died from respiratory failure, although pathology revealed hyaline membranes in the alveoli. Surprisingly, the era of PS replacement therapy began only relatively recently. The first clinical trial investigating neonatal RDS was conducted in 1980. Since then, newborn survival has improved dramatically, which has led to significant advances in the field of neonatology. The present comprehensive review addresses PS, from its discovery to the application of artificial PS in newborns with RDS. It also reviews the history of PS in Korea, including its introduction, various commercial products, present and past research, newborn registries, and health insurance issues. Finally, it describes the inception of the Korean Society of Neonatology and future directions of research and treatment.

Brassinin, a phytoalexin in cruciferous vegetables, suppresses obesity-induced inflammatory responses through the Nrf2-HO-1 signaling pathway in an adipocyte-macrophage co-culture system.

The aim of this study was to investigate the effect of brassinin (BR), a phytoalexin found in plants belonging to the Brassicaceae family, on the obesity-induced inflammatory response and its molecular mechanism in co-culture of 3T3-L1 adipocytes and RAW264.7 macrophages. BR effectively suppressed lipid accumulation by down-regulating the expression of adipogenic factors, which in turn, were regulated by early adipogenic factors such as CCAAT-enhancer-binding protein-ß and Kruppel-like factor 2. Production of inflammatory cytokines and reactive oxygen species, induced by adipocyte-conditioned medium, was significantly decreased in BR-treated cells. This effect of BR was more prominent in contact co-culture of adipocytes and macrophages with a 90% and 34% reduction in IL-6 and MCP-1 levels, respectively. BR also restored adiponectin expression, which was significantly reduced by culturing adipocytes in macrophage-conditioned medium. In the transwell system, BR increased the protein levels of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and its target molecule, hemoxygenase-1 (HO-1), by 55%-93% and 45%-48%, respectively, and also increased Nrf2 translocation into the nucleus. However, knockdown of Nrf2 or HO-1 in RAW264.7 cells restored this BR-mediated inhibition of IL-6 and MCP-1 production. These results indicated that BR inhibited obesity-induced inflammation via the Nrf2-HO-1 pathway.

Dibenzoylmethane, a Component of Licorice, Suppresses Monocyte-to-Macrophage Differentiation and Inflammatory Responses in Human Monocytes and Mouse Macrophages.

The objective of this study was to investigate the effect of dibenzoylmethane (DBM) on monocyte-to-macrophage differentiation, the inflammatory response, and the resulting signaling in human monocytes and murine macrophage. DBM effectively inhibited the monocyte-to-macrophage differentiation induced by phorbol 12-myristate 13-acetate (PMA) through a reduction in adhesion of THP-1 cells. Cluster of differentiation molecule ß (CD11ß) and CD36, which are surface markers of macrophage differentiation, were downregulated by 80 and 74%, respectively. DBM also significantly inhibited lipopolysaccharide (LPS)-induced nitrite (NO) production through the downregulation of inducible oxide synthase (iNOS) in RAW264.7 cells. The abundance of cyclooxygenase-2 (COX-2), a pro-inflammatory protein, was also effectively decreased by DBM in a dose-dependent manner. DBM (50 µM) reduced the levels of COX-2 and iNOS by 81 and 78%, respectively. DBM significantly inhibited the translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), an inflammatory transcription factor, into the nucleus. DBM-mediated increase of NF-κB translocation resulted from the DBM-induced suppression of the phosphorylation of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα). In contrast, DBM effectively increased the expression of nuclear factor E2-related factor 2 (Nrf2) and its target protein, hemeoxygenase-1 (HO-1). Nrf2 translocation into the nucleus was also significantly enhanced by DBM. Furthermore, DBM effectively inhibited the expression of pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1ß), IL-6, and monocyte chemoattractant protein-1 (MCP-1). These results indicated that the DBM-mediated differential regulation of NF-κB and Nrf2, which are major transcription factors involved in inflammation, inhibited the expression of inflammatory cytokines.

Dibenzoylmethane Suppresses Lipid Accumulation and Reactive Oxygen Species Production through Regulation of Nuclear Factor (Erythroid-Derived 2)-Like 2 and Insulin Signaling in Adipocytes.

The aim of this study was to investigate the effects of dibenzoylmethane (1,3-diphenyl-1,3-propanedione, DBM) from licorice roots on lipid accumulation and reactive oxygen species (ROS) production in 3T3-L1 cells. DBM effectively inhibited lipid accumulation during adipogenesis, and its inhibitory effect was shown to be due to the down-regulation of adipogenic factors such as CCAAT-enhancer-binding protein-α (C/EBPα), peroxisome proliferator-activated receptor γ (PPARγ), and fatty acid-binding protein 4 (FABP4). DBM was observed to exert its inhibitory effect on lipid accumulation in the early adipogenic stage (days 0-2) by regulating early adipogenic factors including CCAAT-enhancer-binding protein-ß (C/EBPß) and Krueppel-like factor (KLF) 2. DBM significantly increased the translocation of nuclear factor (erythroid-derived 2)-like 2(Nrf2) into the nucleus, promoting the protein expression of its target gene, heme oxygenase-1 (HO-1). DBM significantly suppressed the insulin-mediated activation of phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt), which are components of insulin signaling. In addition, intracellular ROS production was effectively reduced by DBM treatment, which upregulated antioxidant genes such as glutathione peroxidase (Gpx), catalase (CAT), and superoxide dismutase 1 (SOD1). Furthermore, DBM significantly regulated the expression of the adipokines, resistin and adiponectin. This DBM-mediated regulation of lipid accumulation, ROS production, and adipokine production was shown to be involved in the regulation of the Nrf2 and insulin signaling.

Carl Gustav Jung and Granville Stanley Hall on Religious Experience.

Granville Stanley Hall (1844-1924) with William James (1842-1910) is the key founder of psychology of religion movement and the first American experimental or genetic psychologist, and Carl Gustav Jung (1875-1961) is the founder of the analytical psychology concerned sympathetically about the religious dimension rooted in the human subject. Their fundamental works are mutually connected. Among other things, both Hall and Jung were deeply interested in how the study of religious experience is indispensable for the depth understanding of human subject. Nevertheless, except for the slight indication, this common interest between them has not yet been examined in academic research paper. So this paper aims to articulate preliminary evidence of affinities focusing on the locus and its function of the inner deep psychic dimension as the religious in the work of Hall and Jung.

Safety and immunogenicity of therapeutic DNA vaccine with antiviral drug in chronic HBV patients and its immunogenicity in mice.

BACKGROUND & AIMS: Here, we evaluated the safety and immunogenicity of hepatitis B virus (HBV) DNA vaccine, HB-110, in mice and Korean patients with chronic hepatitis B (CHB) undergoing adefovir dipivoxil (ADV) treatment. METHODS: For animal study, mice (BALB/c or HBV transgenic) were immunized with mHB-110, and T-cell and antibody responses were evaluated. For clinical study, 27 patients randomly received either ADV alone or ADV in combination with HB-110. Liver function tests, serum HBV DNA levels and the presence of HBeAg/anti-HBe were analysed. T-cell responses were estimated by ELISPOT and FACS analysis. RESULTS: mHB-110 induced higher T-cell and antibody responses than mHB-100 in mice. No adverse effects were observed by HB-110 cotreated with ADV. HBV-specific T-cell responses were induced in a portion of patients in medium to high dose of HB-110. Interestingly, HB-110 exhibited positive effects on ALT normalization and maintenance of HBeAg seroconversion. One patient, who received high dose of HB-110 exhibited HBeAg seroconversion during vaccination, which correlated with vaccine-induced T-cell responses without ALT elevation. CONCLUSIONS: HB-110 was safe and tolerable in CHB patients. In contrast to results in animal models, HB-110 in Korean patients exhibited weaker capability of inducing HBV-specific T-cell responses and HBeAg seroconversion than HB-100 in Caucasian patients. As Asian patients, who are generally infected via vertical transmission, appeared to have higher level of immune tolerance than Caucasian, novel approaches for breaking immune tolerance rather than enhancing immunogenicity may be more urgently demanded to develop effective therapeutic HBV DNA vaccines.

Demographic transition in South Korea: implications of falling birth rates.

This review examines the critical issues of declining total fertility rates (TFRs) and aging populations in East Asia with special focus on South Korea. It provides a comprehensive analysis of TFR trends, aging demographics, and the policy responses of these nations to the low-fertility crisis. This study highlights the intricate tapestry of the factors contributing to these demographic shifts, including economic, social, and cultural influences. It also examines the effectiveness of various prenatal policies implemented across these countries, offering insight into their successes and limitations. Furthermore, it explores the role of immigration as a potential solution to the structural challenges posed by low birth rates. This review underscores the importance of multifaceted strategies for addressing the complex demographic challenges faced by South Korea.

Atypical Gradenigo's syndrome in a pediatric case: A critical review of neuroimaging.

Gradenigo's syndrome, a rare but serious complication of otitis media, encompasses a triad of symptoms including otalgia, facial palsy, and abducens nerve palsy, pointing to the involvement of the petrous apex. This case report presents an 11-year-old boy with an atypical manifestation of Gradenigo's syndrome, characterized by the absence of classic features such as abducens nerve palsy and purulent otorrhea. MRI findings were significant for petrous apicitis extending to Meckel's cave and the cavernous sinus, along with abscess formation and clivus osteomyelitis. The report highlights the critical role of advanced neuroimaging, particularly MRI, in the diagnosis and management of this condition. It underscores the importance of recognizing atypical presentations of Gradenigo's syndrome and the effectiveness of imaging-guided conservative treatment strategies in pediatric otological cases.

Mechanical Properties of Cement Mortar Containing Ground Waste Newspaper as Cementitious Material.

In recent years, several studies have reported the recycling of by-products generated by the paper industry and their application to the construction industry. A majority of the existing studies used waste paper sludge ash, and considerable energy is consumed in such incineration processes. This may further contribute to air pollution. In this study, we used waste newspaper (WNP), which underwent a simple crushing process without a separate high-temperature treatment process, and we integrated it in cement mortar. We prepared mortars containing 0%, 0.2%, 0.4%, 0.6%, 0.8%, and 1.0% ground WNP as a cement substitute. Subsequently, the fluidity, compressive strength, tensile strength, carbonation depth, drying shrinkage, and microstructure of the mortars were compared and analyzed. The 28-day compressive strength of the mortar samples with WNP was approximately 3.2-16.1% higher than that of the control sample. The 28-day accelerated carbonation depth of the samples with WNP was approximately 1.03-1.61 mm. Furthermore, their carbonation resistance was approximately 5.2-39.4% higher than that of the control sample. Compressive strength, tensile strength, and carbonation resistance were improved by appropriately using ground WNP as a cement substitute in cement mortar. In this study, the appropriate amount of WNP according to the mechanical properties of cement mortar was found to be 0.4-0.8%, and considering the durability characteristics, the value 0.6 was the most ideal.

Reduction of fetuin-A levels contributes to impairment of Purkinje cells in cerebella of patients with Parkinson's disease.

Phenotypic features such as ataxia and loss of motor function, which are characteristics of Parkinson's disease (PD), are expected to be very closely related to cerebellum function. However, few studies have reported the function of the cerebellum. Since the cerebellum, like the cerebrum, is known to undergo functional and morphological changes due to neuroinflammatory processes, elucidating key functional factors that regulate neuroinflammation in the cerebellum can be a beneficial therapeutic approach. Therefore, we employed PD patients and MPTP-induced PD mouse model to find cytokines involved in cerebellar neuroinflammation in PD and to examine changes in cell function by regulating related genes. Along with the establishment of a PD mouse model, abnormal shapes such as arrangement and number of Purkinje cells in the cerebellum were confirmed based on histological finding, consistent with those of cerebellums of PD patients. As a result of proteome profiling for neuroinflammation using PD mouse cerebellar tissues, fetuin-A, a type of cytokine, was found to be significantly reduced in Purkinje cells. To further elucidate the function of fetuin-A, neurons isolated from cerebellums of embryos (E18) were treated with fetuin-A siRNA. We uncovered that not only the population of neuronal cells, but also their morphological appearances were significantly different. In this study, we found a functional gene called fetuin-A in the PD model's cerebellum, which was closely related to the role of cerebellar Purkinje cells of mouse and human PD. In conclusion, morphological abnormalities of Purkinje cells in PD mice and patients have a close relationship with a decrease of fetuin-A, suggesting that diagnosis and treatment of cerebellar functions of PD patients might be possible through regulation of fetuin-A. [BMB Reports 2023; 56(5): 308-313].

NOX4 as a critical effector mediating neuroinflammatory cytokines, myeloperoxidase and osteopontin, specifically in astrocytes in the hippocampus in Parkinson's disease.

Oxidative stress and mitochondrial dysfunction have been believed to play an important role in the pathogenesis of aging and neurodegenerative diseases, including Parkinson's disease (PD). The excess of reactive oxygen species (ROS) increases with age and causes a redox imbalance, which contributes to the neurotoxicity of PD. Accumulating evidence suggests that NADPH oxidase (NOX)-derived ROS, especially NOX4, belong to the NOX family and is one of the major isoforms expressed in the central nervous system (CNS), associated with the progression of PD. We have previously shown that NOX4 activation regulates ferroptosis via astrocytic mitochondrial dysfunction. We have previously shown that activation of NOX4 regulates ferroptosis through mitochondrial dysfunction in astrocytes. However, it remains unclear why an increase in NOX4 in neurodegenerative diseases leads to astrocyte cell death by certain mediators. Therefore, this study was designed to evaluate how NOX4 in the hippocampus is involved in PD by comparing an MPTP-induced PD mouse model compared to human PD patients. We could detect that the hippocampus was dominantly associated with elevated levels of NOX4 and α-synuclein during PD and the neuroinflammatory cytokines, myeloperoxidase (MPO) and osteopontin (OPN), were upregulated particularly in astrocytes. Intriguingly, NOX4 suggested a direct intercorrelation with MPO and OPN in the hippocampus. Upregulation of MPO and OPN induces mitochondrial dysfunction by suppressing five protein complexes in the mitochondrial electron transport system (ETC) and increases the level of 4-HNE leading to ferroptosis in human astrocytes. Overall, our findings indicate that the elevation of NOX4 cooperated with the MPO and OPN inflammatory cytokines through mitochondrial aberration in hippocampal astrocytes during PD.