Development of a dual immunochromatographic test strip to detect E2 and Erns antibodies against classical swine fever.

Background: It is essential to consider a practical antibody test to successfully implement marker vaccines and validate vaccination efficacy against classical swine fever virus (CSFV). The test should include a serological antibody assay, combined with a tool for differentiating infected from vaccinated animals (DIVA). The immunochromatographic test strip (ICS) has been exclusively designed for detecting CSFV E2 antibodies while lacking in detecting Erns antibodies, which can be employed and satisfy DIVA strategy. This study developed a novel ICS for detecting CSFV E2/Erns dual-antibody. The effectiveness of ICS in evaluating the DIVA capability of two novel chimeric pestivirus vaccine candidates was assessed. Methods: Recombinant E2 or Erns protein was transiently expressed in the plant benthamiana using Agrobacterium tumefaciens. ICS was subsequently assembled, and goat anti-rabbit IgG and recombinant CSFV E2 or Erns protein were plated onto the nitrocellulose membrane as control and test lines, respectively. The sensitivity and specificity of ICS were evaluated using sera with different neutralizing antibody titers or positive for antibodies against CSFV and other pestiviruses. The coincidence rates for detecting E2 and Erns antibodies between ICS and commercial enzyme-linked immunosorbent assay (ELISA) kits were also computed. ICS performance for DIVA capability was evaluated using sera from pigs vaccinated with conventional vaccine or chimeric vaccine candidates. Results: E2 and Erns proteins were successfully expressed in N. benthamiana-produced recombinant proteins. ICS demonstrated high sensitivity in identifying CSFV E2 and Erns antibodies, even at the low neutralizing antibody titers. No cross-reactivity with antibodies from other pestiviruses was confirmed using ICS. There were high agreement rates of 93.0 and 96.5% between ICS and two commercial ELISA kits for E2 antibody testing. ICS also achieved strong coincidence rates of 92.9 and 89.3% with two ELISA kits for Erns antibody detection. ICS confirmed the absence of CSFV Erns-specific antibodies in sera from pigs vaccinated with chimeric vaccine candidates. Conclusion: E2 and Erns proteins derived from the plant showed great potential and can be used to engineer a CSFV E2/Erns dual-antibody ICS. The ICS was also highly sensitive and specific for detecting CSFV E2 and Erns antibodies. Significantly, ICS can fulfill the DIVA concept by incorporating chimeric vaccine candidates.

Worrying about our children: Parental worry and psychological well-being among Korean middle-aged couples.

When children reach a certain age of maturity, middle-aged parents often reflect on their parenting, harboring continuous worries about their adult children. These parenting experiences are also shared within couples and continue to impact parents' well-being. Utilizing couple data from the 2010 Korean Baby Boomer Panel Study, we examined the dyadic associations of worry about child issues and psychological well-being among middle-aged couples (N = 1,091; aged 47-55) who have at least one adult child (Mage = 23.13 years). Results from the actor-partner interdependence model showed that one's own parental worry was significantly associated with psychological well-being for both husbands and wives (i.e., actor effects). Further, wives' worry about children was significantly associated with husbands' psychological well-being (i.e., partner effects)-but not vice versa. These findings highlight that aspects of parenting not only impact children but also extend to the linked lives of midlife parents themselves. Research on parental experiences at the couple level may inform interventions to enhance middle-aged parents' well-being. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Efficacy and safety of HIP1601 (dual delayed-release esomeprazole) 40 mg in erosive esophagitis compared to HGP1705 (delayed-release esomeprazole) 40 mg: a multicenter, randomized, double-blind, non-inferiority study.

BACKGROUND: Proton-pump inhibitors (PPIs) are the most effective drugs for treating acid-related disorders. However, once-daily dosing with conventional PPIs fail to fully control acid secretion over 24 h. This study aimed to compare the efficacy and safety of HIP1601 (dual delayed-release esomeprazole) and HGP1705 (delayed-release esomeprazole) in patients with erosive esophagitis (EE). METHODS: We enrolled 213 patients with EE randomized in a 1:1 ratio to receive 40 mg HIP1601 (n = 107) or HGP1705 (n = 106) once daily for 4 or 8 weeks. The primary endpoint was the EE healing rate, confirmed by endoscopy up to week 8. GERD-related symptoms and treatment-emergent adverse events were compared between both groups. RESULTS: By week 8, the estimated healing rates of EE were 97.8% and 96.8% in the HIP1601 and HGP1705 groups, respectively, with a 95% confidence interval of -4.7 to 7.2. After 4 or 8 weeks of treatment, the EE healing rate at week 4, complete resolution rate of symptoms, time to sustained resolution of symptoms, and number of rescue medications used were similar in both groups. The proportion of heartburn- and acid regurgitation-free nights by week 4 were higher in the HIP1601 group compared to the HGP1705 group, but the difference did not reach clinical significance (87.7% vs. 85.8%, P = 0.514, 87.5% vs. 85.8%, P = 0.774). The number of adverse events did not differ significantly between the two groups. CONCLUSIONS: The efficacy and safety of HIP1601 40 mg were comparable to those of HGP1705 40 mg for the treatment of EE and symptomatic improvement of GERD. TRIAL REGISTRATION: NCT04080726 ( https://classic. CLINICALTRIALS: gov/ct2/show/NCT04080726 ), registration date: 25/10/2018.

Fatal Primary Amebic Meningoencephalitis due to Naegleria fowleri: The First Imported Case in Korea.

Primary amebic meningoencephalitis (PAM) is a rare, but almost always fatal, central nervous system infection caused by Naegleria fowleri, which are thermophilic free-living amoeba. Here, we report the first case of PAM detected in South Korea, probably imported from Thailand. Despite antimicrobial treatment for N. fowleri infection with a combination of intravenous liposomal amphotericin B, fluconazole, azithromycin, and oral rifampin, the patient died 13 days after the onset of symptoms. Clinicians in South Korea treating severe meningoencephalitis, especially in individuals returning from tropical areas, are encouraged to include PAM in the differential diagnoses, given the accelerated global warming and increased overseas trips.

Kudoa septempunctata Spores Cause Acute Gastroenteric Symptoms in Mouse and Musk Shrew Models as Evidenced In Vitro in Human Colon Cells.

Kudoa septempunctata is a myxosporean parasite that infects the trunk muscles of olive flounder (Paralichthys olivaceus) and has been reported to cause foodborne illnesses in humans. However, the molecular mechanisms underlying K. septempunctata spore toxicity remain largely unknown. In this study, the gastroenteropathy of K. septempunctata was examined in human colon adenocarcinoma cells as well as experimental mice inoculated with spores. We found that K. septempunctata decreased transepithelial resistance and disrupted epithelial tight junctions by deleting ZO-1 in Caco-2 monolayers. Additionally, serotonin (5-HT), an emetic neurotransmitter, was increased in K. septempunctata-inoculated cells. In vivo, K. septempunctata spores induced diarrhea in suckling mice (80% in ddY and 70% in ICR mice), with a minimum provocative dose of 2 × 105 K. septempunctata spores. In house musk shrews, K. septempunctata induced emesis within 1 h and induced serotonin secretion in the intestinal epithelium. In conclusion, K. septempunctata may induce diarrhea and emesis by increasing intestinal permeability and serotonin secretion.

Pharmacokinetic Interactions Between Bazedoxifene and Cholecalciferol: An Open-Label, Randomized, Crossover Study in Healthy Male Volunteers.

Purpose: The combined administration of bazedoxifene, a tissue-selective estrogen receptor modulator, and cholecalciferol can be a promising therapeutic option for postmenopausal osteoporosis patients. This study aimed to examine the pharmacokinetic interactions between these two drugs and the tolerability of their combined administration in healthy male subjects. Patients and Methods: Thirty male volunteers were randomly assigned to one of the six sequences comprised of three treatments: bazedoxifene 20 mg monotherapy, cholecalciferol 1600 IU monotherapy, and combined bazedoxifene and cholecalciferol therapy. For each treatment, a single dose of the investigational drug(s) was administered orally, and serial blood samples were collected to measure the plasma concentrations of bazedoxifene and cholecalciferol. Pharmacokinetic parameters were calculated using the non-compartmental method. The point estimate and 90% confidence interval (CI) of the geometric mean ratio (GMR) were obtained to compare the exposures of combined therapy and monotherapy. The pharmacokinetic parameters compared were the maximum plasma concentration (Cmax) and the area under the plasma concentration-time curve from time zero to the last quantifiable concentration (AUClast). The safety and tolerability of the combined therapy were assessed in terms of the frequency and severity of adverse events (AEs). Results: For bazedoxifene, the GMR (90% CI) of the combined therapy to monotherapy was 1.044 (0.9263-1.1765) for Cmax and 1.1329 (1.0232-1.2544) for AUClast. For baseline-adjusted cholecalciferol, the GMR (90% CI) of the combined therapy to monotherapy was 0.8543 (0.8005-0.9117) for Cmax and 0.8056 (0.7445-0.8717) for AUClast. The frequency of AEs observed was not significantly different between the combined therapy and monotherapy, and their severity was mild in all cases. Conclusion: A mild degree of pharmacokinetic interaction was observed when bazedoxifene and cholecalciferol were administered concomitantly to healthy male volunteers. This combined therapy was well tolerated at the dose levels used in the present study.

Pharmacokinetics and Pharmacodynamics of Esomezol DR, a New Dual Delayed-Release Formulation of Esomeprazole 20 Mg or 40 Mg, in Healthy Subjects.

Background: Esomeprazole, a proton pump inhibitor (PPI), is widely used to treat acid-related disorders, but it has short plasma half-life which can cause insufficient gastric acid suppression, such as nocturnal acid breakthrough. A new dual delayed-release (DR) formulation of esomeprazole (Esomezol DR), was developed to extend the duration of gastric acid suppression. Purpose: This study aimed to evaluate the pharmacokinetics (PKs) and pharmacodynamics (PDs) of esomeprazole for the DR formulation compared to a conventional enteric-coated (EC) formulation (Nexium) in healthy male subjects. Methods: Two randomized, open-label, multiple-dose, two-way crossover studies with esomeprazole 20 mg and 40 mg were conducted. Subjects received the DR formulation or the EC formulation once daily for 7 days in each period with a 7-day washout. Serial blood samples were collected up to 24 hours after the 1st dose, and 24-hour intragastric pH was continuously monitored before the 1st dose as baseline and after the 1st and the 7th dose. Results: In 20 mg and 40 mg dose groups, 38 and 44 subjects completed the study, respectively. The DR formulation exhibited the dual-release pattern of esomeprazole, resulting in more sustained plasma concentration-time profiles compared to the EC formulation. The systemic exposure of esomeprazole for the DR formulation was comparable to that for the EC formulation, showing the similar area under the plasma concentration-time curve. The 24-hour gastric acid suppression was also similar between the two formulations, while the inhibition during night-time (22:00-06:00) showed a better tendency in the DR formulation. Conclusion: The sustained exposure of esomeprazole in the DR formulation led to well-maintained and higher acid inhibition compared to the EC formulation, especially during the night-time. These results suggest that the DR formulation can be an alternative formulation to the conventional EC formulation, expecting the potential of relieving nocturnal acid-related symptoms.

Effect of Food on the Pharmacokinetics and Pharmacodynamics of a Novel Dual Delayed-Release Formulation of Esomeprazole in Healthy Subjects.

A novel dual delayed-release formulation (DR) of esomeprazole was developed to prolong the effect of esomeprazole inhibiting gastric acid secretion. This study investigated the effect of food on the pharmacokinetics (PK) and pharmacodynamics (PD) of DR esomeprazole. A randomized, open-label, single-dose, 2-period, 2-sequence crossover study was conducted in healthy Korean subjects. Subjects were orally administered a single dose of 40- mg DR esomeprazole in fasted and fed states in each period. PK and PD characteristics evaluated through continuous 24-hour intragastric pH monitoring in fasted and fed states were compared between the 2 conditions. A total of 23 subjects completed the study and were included in the PK analysis. PD analysis was conducted in 21 subjects, excluding 2 subjects, because of inappropriate pH profiles. The systemic exposure of esomeprazole after a single dose of DR esomeprazole in the fed state decreased compared to that in the fasted state. However, the percentage decrease from baseline in integrated gastric acidity and the percentage of time at pH ≥4 were not significantly different between the 2 conditions. In conclusion, although the systemic exposure of esomeprazole decreased when DR esomeprazole was administered in the fed state compared to that in the fasted state, the degree of gastric acid secretion inhibition was not clinically different, regardless of food intake.

Microfluidic model for in vitro acute Toxoplasma gondii infection and transendothelial migration.

The protozoan parasite Toxoplasma gondii (T. gondii) causes one of the most common human zoonotic diseases and infects approximately one-third of the global population. T. gondii infects nearly every cell type and causes severe symptoms in susceptible populations. In previous laboratory animal studies, T. gondii movement and transmission were not analyzed in real time. In a three-dimensional (3D) microfluidic assay, we successfully supported the complex lytic cycle of T. gondii in situ by generating a stable microvasculature. The physiology of the T. gondii-infected microvasculature was monitored in order to investigate the growth, paracellular and transcellular migration, and transmission of T. gondii, as well as the efficacy of T. gondii drugs.

All-in-one encoder/decoder approach for non-destructive identification of 3D-printed objects.

This paper presents an all-in-one encoder/decoder approach for the nondestructive identification of three-dimensional (3D)-printed objects. The proposed method consists of three parts: 3D code insertion, terahertz (THz)-based detection, and code extraction. During code insertion, a relevant one-dimensional (1D) identification code is generated to identify the 3D-printed object. A 3D barcode corresponding to the identification barcode is then generated and inserted into a blank bottom area inside the object's stereolithography (STL) file. For this objective, it is necessary to find an appropriate area of the STL file and to merge the 3D barcode and the model within the STL file. Next the information generated inside the object is extracted by using THz waves that are transmitted and reflected by the output 3D object. Finally, the resulting THz signal from the target object is detected and analyzed to extract the identification information. We implemented and tested the proposed method using a 3D graphic environment and a THz time-domain spectroscopy system. The experimental results indicate that one-dimensional barcodes are useful for identifying 3D-printed objects because they are simple and practical to process. Furthermore, information efficiency can be increased by using an integral fast Fourier transform to identify any code located in areas deeper within the object. As 3D printing is used in various fields, the proposed method is expected to contribute to the acceleration of the distribution of 3D printing empowered by the integration of the internal code insertion and recognition process.

Comparison of Suicide Attempts and Suicide Deaths by Jumping from a High Place in Korean Children and Adolescents.

Jumping from a high place is the most common method of suicide among Korean children and adolescents. The aim of this study was to examine the personal, family, and school life of Korean children and adolescents who chose jumping from a high place, among suicide attempts and suicide deaths, based on teachers' reports. Data on suicide attempts and suicide deaths by jumping from a high place in children and adolescents were collected through the Ministry of Education in South Korea from 2016 to 2018. We compared sociodemographic variables, suicide-related variables, emotional and behavioral status, school life related variables, and variables related to family problems among suicide deaths (n = 262), actual suicide attempts (n = 50), and interrupted or aborted suicide attempts (n = 210). There were differences in educational stage (p < 0.001), place of suicide (p < 0.001), presence of suicide note (p < 0.05) and previous suicide attempt (p < 0.001) among the three groups. The total difficulty score on the Strength Difficulty Questionnaire of interrupted or aborted suicide attempts was higher than that of the other two groups. Our study suggests that the suicide death group tend to present fewer personal and family pathologies and better school adjustment than the suicide attempt group.

Understanding The Health Landscapes Where Latinx Immigrants Establish Residence In The US.

The diversity of health contexts in which members of the US Latinx population establish residence may provide insights into the variety of health challenges they face. We investigated differences in health professional shortages, general health services, health care safety-net supply, health access, and population health rankings across 3,113 US counties classified as established, new, or other Latinx population destinations. Compared with new destinations, established destinations had more health professional shortages, as well as higher rates of child and adult health uninsurance. New destinations had fewer health care safety-net services per 100,000 county residents than established destinations. Health contexts thus differ in significant ways across new and established Latinx destinations, and these differences have key implications for Latinx immigrant health.

PB01 suppresses radio-resistance by regulating ATR signaling in human non-small-cell lung cancer cells.

Despite the common usage of radiotherapy for the treatment of human non-small-cell lung cancer (NSCLC), cancer therapeutic efficacy and outcome with ionizing radiation remains a challenge. Here, we report the antitumor effects and mechanism of a novel benzothiazole derivative PB01 (4-methoxy-cyclohexane carboxylic acid [2-(3,5-dimethyl-isoxazole-4-yl) sulpanil-benzothiazole-6-yl]-amide) in radiation-resistant human NSCLC cells. PB01 treatment is cytotoxic because it induces reactive oxygen species, ER stress, Bax, cytochrome c expression, the ATR-p53-GADD45ɑ axis, and cleavage of caspase-3 and -9. Additionally, we found that radio-resistant A549 and H460 subclones, named A549R and H460R, respectively, show enhanced epithelial-to-mesenchymal transition (EMT), whereas PB01 treatment inhibits EMT and mediates cell death through ER stress and the ATR axis under radiation exposure in radio-resistant A549R and H460R cells. Together, these results suggest that PB01 treatment can overcome radio-resistance during radiotherapy of NSCLC.

The Novel Benzothiazole Derivative PB11 Induces Apoptosis via the PI3K/AKT Signaling Pathway in Human Cancer Cell Lines.

Among several anti-cancer therapies, chemotherapy can be used regardless of the stage of the disease. However, development of anti-cancer agents from potential chemicals must be executed very cautiously because of several problems, such as safety, drug resistance, and continuous administration. Most chemotherapeutics selectively cause cancer cells to undergo apoptosis. In this study, we tested the effects of a novel chemical, the benzothiazole derivative N-[2-[(3,5-dimethyl-1,2-oxazol-4-yl)methylsulfanyl]-1,3-benzothiazol-6-yl]-4-oxocyclohexane-1-carboxamide (PB11) on the human cell lines U87 (glioblastoma), and HeLa (cervix cancer). It was observed that this chemical was highly cytotoxic for these cells (IC50s < 50 nM). In addition, even 40 nM PB11 induced the classical apoptotic symptoms of DNA fragmentation and nuclear condensation. The increase of caspase-3 and -9 activities also indicated an increased rate of apoptosis, which was further confirmed via Western blotting analysis of apoptosis-associated proteins. Accordingly, PB11 treatment up-regulated the cellular levels of caspase-3 and cytochrome-c, whereas it down-regulated PI3K and AKT. These results suggest that PB11 induces cytotoxicity and apoptosis in cancer cells by suppressing the PI3K/AKT signaling pathways and, thus, may serve as an anti-cancer therapeutic.

The Impact of Referral to Mental Health Services on Suicide Death Risk in Adolescent Suicide Survivors.

OBJECTIVES: This study aims to examine the effect of adolescent suicide survivors' experience on suicide death risk, and the effect of referral to mental health services (hereafter referral) in this regard. METHODS: This study used the data of 878 suicide-deceased and suicide-attempted adolescents aged 8-19 years, managed by the Suicide and School Mental Health Institute from 2016 to 2018. RESULTS: Regression analysis for main effects showed that although suicide experience had no direct effect on suicide death, non-referral status was associated with a greater risk of death by suicide. While the "non-suicide survivor with non-referral" and "suicide survivor with non-referral" groups showed 1.87 [adjusted odds ratio=1.87, 95% confidence interval (CI)=1.21-2.89] and 4.59 (adjusted odds ratio= 4.59, 95% CI=2.02-10.42) times higher odds of suicide death, respectively, the "suicide survivor with referral" group showed no difference compared to the "non-suicide survivor with referral" group. CONCLUSION: From these findings, there is a need to strengthen referral to mental health services and apply complicated grief treatment to improve the mental health of adolescent suicide survivors.

Characteristics of First Visit Pediatric Patients with Suicidal Ideation and Behavior: An 8-Year Retrospective Chart Review.

OBJECTIVES: Our study aimed to analyze the demographic and clinical characteristics of children and adolescents during their first visit to psychiatric outpatient departments for the management of suicidal ideation and behavior, and to compare the changes before and in 2012 or later. METHODS: This multicenter study was conducted at five university hospitals in a metropolitan area in South Korea. Medical records of patients aged 6-18 years were retrospectively reviewed from January 2009 to December 2016. Patients were analyzed by classifying them into suicidal and non-suicidal groups based on their visit to the hospital for management of suicidal ideation or suicide attempt and other mental problems, respectively. RESULTS: There were differences in the year of visit, diagnosis, education level, and referral sources between patients in the suicidal and non-suicidal groups. Multiple regression analysis was conducted based on the sex, education level, referral by school, and diagnosis of depression in patients in the suicidal group, which revealed significant association. CONCLUSION: Suicide-related problems were significantly associated with the sex, education level, referral by school, and a diagnosis of depression in the patients. A well-connected referral system would be necessary for professional mental health management of high-risk children and adolescents.

A novel PPARÉ£ ligand, PPZ023, overcomes radioresistance via ER stress and cell death in human non-small-cell lung cancer cells.

Peroxisome proliferator-activated receptor gamma (PPARÉ£) agonists exert powerful anticancer effects by suppressing tumor growth. In this study, we developed PPZ023 (1-(2-(ethylthio)benzyl)-4-(2-methoxyphenyl)piperazine), a novel PPAR ligand candidate, and investigated the underlying signaling pathways in both non-small-cell lung cancer (NSCLC) and radio-resistant NSCLC cells. To identify whether PPZ023 has anticancer effects in NSCLC and radioresistant NSCLC cells, we performed WST-1, LDH, Western blot, and caspase-3 and -9 activity assays. Furthermore, we isolated exosomes from PPZ023-treated NSCLC cells and studied cell death signaling. PPZ023 reduces cell viability and increases LDH cytotoxicity and caspase-3 activity in NSCLC cells. PPZ023 induces cell death by generating reactive oxygen species (ROS) and triggering mitochondrial cytochrome c release. PPZ023 treatment causes cell death via the PERK-eIF2α-CHOP axis in both NSCLC cell lysates and exosomes, and PERK and CHOP knockdown significantly blocks ER stress-mediated apoptosis by reducing cleaved caspase-3. Interestingly, diphenyleneiodonium (DPI, a Nox inhibitor) inhibits PPZ023-induced cell death via ER stress, and PPARÉ£ knockdown inhibits PPZ023-induced ROS, ER stress, and cell death. Moreover, PPZ023, in combination with radiation, causes synergic cell death via exosomal ER stress in radioresistant NSCLC cells, indicating that PPZ023/radiation overcomes radioresistance. Taken together, our results suggest that PPZ023 is a powerful anticancer reagent for overcoming radioresistance.

CB13, a novel PPARγ ligand, overcomes radio-resistance via ROS generation and ER stress in human non-small cell lung cancer.

Peroxisome proliferator-activated receptor gamma (PPARγ) is a well-known therapeutic target for type 2 diabetes as well as is a potential target for effective anti-cancer drug, since PPARγ ligands such as ciglitazone (Cig) frequently cause cell death in many types of cancer cells and suppress tumor growth. However, many cancer patients acquire chemo-resistance or radio-resistance after chemo or radiotherapy, and it is still unclear. In the difficulty of well-known anti-cancer drugs, we developed a novel PPARγ agonist CB13 (1-benzyl-5-(4-methylphenyl) pyrido [2,3-d]pyrimidine-2,4(1H,3H)-dione) and investigated the anti-cancer effect and cell death mechanism on human non-small cell lung cancer (NSCLC) cells. With anti-cancer effect of Cig, CB13 also causes inhibition of cell growth by decreasing cell viability, increasing the release of LDH, and increasing caspase-3, and caspase-9 activities. CB13 generates reactive oxygen species (ROS) and causes cell death via ER stress in NSCLC and radio-resistant NSCLC cells (A549R and H460R), and a combination of CB13 and radiation induces greater ER stress and cell death when compared to CB13 alone. Taken together, our results suggest that a combination of CB13 and radiation may overcome radio-resistance caused by radiotherapy.

CB11, a novel purine-based PPARÉ£ ligand, overcomes radio-resistance by regulating ATM signalling and EMT in human non-small-cell lung cancer cells.

BACKGROUND: Peroxisome proliferator-activated receptor γ (PPARγ) agonists frequently induce cell death in human non-small-cell lung cancer (NSCLC) cells. However, majority of NSCLC patients acquire resistance after cancer therapy, and it is still unclear. METHODS: In this study we investigated the apoptotic mechanism and the anti-cancer effects of a novel purine-based PPARγ agonist, CB11 (8-(2-aminophenyl)-3-butyl-1,6,7-trimethyl-1H-imidazo[2,1-f]purine-2,4(3H,8H)-dione), on human NSCLC cells. CB11 mediates PPARγ-dependent cell death, reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP) collapse, cell cycle arrest, lactate dehydrogenase (LDH) cytotoxicity, and caspase-3 activity in human NSCLC cells. RESULTS: CB11 causes cell death via ROS-mediated ATM-p53-GADD45α signalling in human NSCLC cells, and diphenyleneiodonium (DPI), an NADPH oxidase inhibitor, decreases cell death by inhibiting CB11-mediated ATM signalling. In a xenograft experiment, CB11 dramatically reduced tumour volume when compared to a control group. Furthermore, CB11 induced cell death by inhibiting epithelial-to-mesenchymal transition (EMT) under radiation exposure in radiation-resistant human NSCLC cells. However, PPARγ deficiency inhibited cell death by blocking the ATM-p53 axis in radiation/CB11-induced radiation-resistant human NSCLC cells. CONCLUSIONS: Taken together, our results suggest that CB11, a novel PPARγ agonist, may be a novel anti-cancer agent, and it could be useful in a therapeutic strategy to overcome radio-resistance in radiation-exposed NSCLC.

Modelling Toxoplasma gondii infection in human cerebral organoids.

Pluripotent stem cell-derived cerebral organoids have the potential to recapitulate the pathophysiology of in vivo human brain tissue, constituting a valuable resource for modelling brain disorders, including infectious diseases. Toxoplasma gondii, an intracellular protozoan parasite, infects most warm-blooded animals, including humans, causing toxoplasmosis. In immunodeficient patients and pregnant women, infection often results in severe central nervous system disease and fetal miscarriage. However, understanding the molecular pathophysiology of the disease has been challenging due to limited in vitro model systems. Here, we developed a new in vitro model system of T. gondii infection using human brain organoids. We observed that tachyzoites can infect human cerebral organoids and are transformed to bradyzoites and replicate in parasitophorous vacuoles to form cysts, indicating that the T. gondii asexual life cycle is efficiently simulated in the brain organoids. Transcriptomic analysis of T. gondii-infected organoids revealed the activation of the type I interferon immune response against infection. In addition, in brain organoids, T. gondii exhibited a changed transcriptome related to protozoan invasion and replication. This study shows cerebral organoids as physiologically relevant in vitro model systems useful for advancing the understanding of T. gondii infections and host interactions.