Association between Masticatory Performance, Nutritional Intake, and Frailty in Japanese Older Adults.

The older adult population in Japan is expected to increase. Therefore, long-term care and frailty prevention are important. However, the relationship between masticatory performance, nutritional intake, and frailty remains unclear. This cross-sectional study aimed to examine energy, protein, and vitamin D intake and its association with frailty and masticatory performance in older adults. Patients between January 2022 and January 2023 were recruited and divided into robust and frail groups. Masticatory performance, nutrition, frailty, and other data, such as age and sex, were evaluated through onsite measurements and a questionnaire. Logistic regression analysis was conducted with frailty as a dependent variable and masticatory performance as an independent variable, adjusting for age, sex, skeletal muscle mass, living alone, energy intake, protein-energy ratio, and vitamin D intake. No significant differences were observed between the groups regarding age or sex. The robust group showed significantly better results for protein-energy ratio, vitamin D intake, and subjective and objective masticatory performance than the frail group. Logistic regression analysis revealed a significant correlation between skeletal muscle mass, protein-energy ratio, and objective masticatory performance with frailty. Masticatory performance was associated with frailty, independent of the intake of nutrients such as energy, protein, and vitamin D.

Association between periodontal disease and chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) and periodontal disease are chronic inflammatory conditions that significantly affect an individual's overall health and well-being. Generally, the prevalence of periodontitis is higher in patients with COPD than those without COPD, which may partly be attributed to common risk factors in COPD, such as smoking, respiratory infections, and inflammation. In particular, periodontitis may exacerbate the progression of COPD and further deteriorate the respiratory system by promoting inflammatory responses and bacterial infections. Immunocytes, including neutrophils, and microorganisms such as Fusobacterium nucleatum originating from oral biofilms are believed to be crucial factors influencing to COPD. Furthermore, the potential benefits of treating periodontal disease in COPD outcomes have been investigated. Although the relationship between COPD and periodontal disease has been preliminarily studied, there is currently a lack of large-scale clinical studies to validate this association. In addition to clinical examinations, investigating biomarkers and microbiology may contribute to explore the underlying mechanisms involved in the management of these conditions. This review aims to contribute to a better understanding of the clinical and basic research aspects of COPD and periodontitis, allowing for potential therapeutic approaches and interdisciplinary management strategies.

Detection of lisdexamfetamine and its metabolite d-amphetamine in urine and gastric contents collected from a cadaver at forensic autopsy.

PURPOSE: Lisdexamfetamine (LDX), which is used for the treatment of attention-deficit/hyperactivity disorder and narcolepsy, is composed of L-lysine attached to dextroamphetamine (d-amphetamine). In this article, we report a forensic autopsy case in which prescription drugs were unknown at autopsy. While amphetamine was detected, methamphetamine could not be detected by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in any of samples collected. Thus, we aimed to quantify LDX concentrations in autopsy samples and to prove that the amphetamine detected in this case was due to metabolized LDX. METHODS: Femoral vein blood, cardiac whole blood, urine, and gastric content samples were taken at autopsy for toxicological analysis. Qualitative and quantitative analyses were performed using LC-MS/MS. In addition, optical isomer separation for the amphetamine detected was conducted. The stability of LDX in whole blood and urine was also examined at three different temperatures. RESULTS: The concentrations of LDX were < 4.00, 30.9, and 4.42 ng/mL in whole blood, urine, and gastric content samples, respectively. The concentrations of amphetamine were 329, 510, 2970, and 915 ng/mL in femoral vein blood, heart whole blood, urine, and gastric contents, respectively. The amphetamine detected in this case was identified to be only d-amphetamine by optical isomer separation. The d-amphetamine detected was considered to be derived from LDX. Stability experiments revealed that LDX in whole blood decreased at ambient temperature. CONCLUSIONS: The results in the present case report may be useful in interpreting whether or not the amphetamine detected in a cadaver is a metabolite of LDX.

Factors Affecting the Career Continuation of Newly Graduated and Reinstated Dental Hygienists Who Participated in a Technical Training Program in Japan.

This study aimed to identify (1) what newly graduated dental hygienists and reinstated dental hygienists consider important for preventing early turnover in their own professions and for encouraging them to continue in the profession more generally and (2) relevant factors among hygienists intending to continue working in the field. An anonymous, self-administered questionnaire survey was distributed to 215 Japanese dental hygienists who participated in the technical training programs (response rate: 72.6%). Of them, 143 participants were classified into two groups: newly graduated (NGDH, n = 32) and those reinstated to work (RDH, n = 111). Follow-up for lack of skills was most often selected as important for preventing early turnover among both groups and follow-up for lack of knowledge was significantly selected in the RDH group (p < 0.001). Regarding factors important for career continuation, NGDHs significantly selected gaining job satisfaction, whereas RDHs significantly selected working support. Relevant factors contributing to participants' intentions to continue in the profession were job satisfaction (NGDH, OR = 8.37; RDH, OR = 8.83), career outlook (RDH, OR = 3.11), and job turnover experience because of marriage and parenting (RDH, OR = 2.70), thereby suggesting the importance of raising awareness regarding career progression and job-related rewards among dental hygienists, their educators, and the government through ongoing career education.

Simple and simultaneous quantification of cyanide, ethanol, and 1-propanol in blood by headspace GC-MS/NPD with Deans switch dual detector system.

Cyanide is a powerful and rapidly acting poison. In Japan, cyanide poisoning is rare, and regular cyanide testing can be costly and time consuming. In contrast, alcohol analysis is routinely performed in most forensic laboratories. In this study, we attempted to develop a method for the simultaneous quantification of cyanide and alcohols in blood using headspace gas chromatography (HS-GC). As nitrogen-phosphorus detection (NPD) is more sensitive to hydrogen cyanide than mass spectrometry (MS), a Deans switch was used to switch the detectors during a single run. The separation provided by three analytical columns, PoraBOND Q, CP-Sil 5 CB, and HP-INNOWax, was investigated, and PoraBOND Q was selected. The use of HS-GC-MS/NPD with a Deans switch enabled the simple and simultaneous quantification of cyanide, ethanol, and 1-propanol. Eighteen other volatile compounds were detected in the SIM/scan mode of the MS.

The Effects of Providing Advance Notice and Stress-Coping Traits on Physiological Stress of Patients during Dental Treatment.

Patients tend to feel stress in association with dental treatment due to uneasiness and fear. We investigated the effects of providing advance notice and stress-coping traits on the physiological stress of patients during dental treatment. Sixty non-dental professionals (male, n = 26; female, n = 34; mean age, 49.9 years) were recruited for this study and informed consent was obtained. Subjects were given simulated dental treatment including three stimuli, air, percussion and running of an air turbine, with or without advance notice of the stimulation during dental treatment. Real-time sympathetic nerve activity (SN) and parasympathetic nerve activity (PN) during the treatment were measured using a biological information monitor. The stress-coping traits of each subject were examined using the Lazarus-Type Stress Coping Inventory (SCI). Correlations between the nerve-activity and scores of eight stress-coping strategies of SCI and the presence/absence of advance notice were analyzed. Age, types of stimuli and order of stimuli significantly affected SN, while age, types of stimuli, and the pattern of stimulation significantly affected PN. The interaction of the stress-coping trait and presence/absence of advance notice significantly affected PN. Providing advance notice may have different effects on physiological stress depending on how the patient copes with stress.

A survey of oral health status, subjective oral symptoms and oral health behaviors among first-year dental students at a Japanese university.

PURPOSE: The rapid deterioration of oral health in young adults is an alarming problem in Japan. The aim of the present study is to investigate the oral health status, subjective oral symptoms and oral health behaviors of dental students. METHODS: Participants were 108 first-year students attending dental school in 2018-2019. Oral examinations were performed to assess dental caries indices, oral hygiene status, gingival bleeding on probing (BOP) and pocket depth. A self-administered questionnaire was used to assess subjective oral symptoms and oral health behaviors. RESULTS: The prevalence of decayed teeth (DT) and gingivitis (BOP ≥ 10%) were 43.5% and 50.0%, respectively. Having DT and gingivitis were significantly associated with poorer oral hygiene. No association was observed between DT and subjective symptoms. Having gingivitis was significantly associated with xerostomia, mouth-breathing and less use of interdental cleaning tools. Multiple logistic regression analysis for gingivitis yielded an odds ratio of 1.41 (95% confidence interval: 1.19-1.67) for plaque score, and 2.75 (1.27-5.98) for xerostomia. CONCLUSION: Since a relatively high ratio of students had DT and gingivitis without clear subjective symptoms, they require regular dental visits for early treatment and oral hygiene maintenance from the start of their time at university.

Relationship between career education experience among final-year dental hygiene students and their perspective towards work and profession: A nationwide survey in dental hygiene schools of Japan.

OBJECTIVES: This study aimed to clarify the relationship between the experience of receiving career education among final-year dental hygiene students and their views regarding their work and profession, as part of research on the working style of dental hygienists. METHODS: An anonymous, self-administered survey was sent by post to all the 162 dental hygienist schools in Japan with dental hygiene students in their final year in November 2019. The main questions were regarding student attributes, career aspirations, their perspective on work and profession and whether or not they received career education at a dental hygienist training school. Analysis was conducted by cross-tabulation and logistic regression. RESULTS: Completed questionnaires were sent to us by 150 schools (response rate 92.6%), with a response from 6,270 students. The students who had received career education had significantly higher awareness and plans for the profession and a positive attitude towards the work (p < 0.01). Following adjustment for age, sex, educational attainment, length of the course of study and timing of class the results shows that there was a significant relation between the experience of the career education with having future plans (odds ratio = 2.11, 95% confidence interval = 1.88-2.38, p < 0.01). CONCLUSIONS: It was observed that the experience of receiving career education just before graduating from dental hygienist school was related to an increased positive attitude of the students towards their work and profession. Further long-term investigations are necessary to evaluate the effects of career education among dental hygiene students and their attitude towards their profession.

A mixed methods study on the readiness of dental, medical, and nursing students for interprofessional learning.

BACKGROUND: Interprofessional education (IPE) is crucial in dentistry, medicine, and nursing. However, scant mixed methods studies have compared the IPE outcomes across these disciplines to develop evidence-based IPE. This study explored the differences in the readiness of dental, medical, and nursing students for interprofessional learning before and after IPE workshops and elucidated reasons for this disparity. METHODS: Data were obtained from dental, medical, and nursing students who participated in IPE workshops conducted at Tokyo Medical and Dental University in Japan in 2019 and 2020. The participants filled the validated Japanese version of the Readiness for Interprofessional Learning Scale (RIPLS) before and after attending the workshops (n = 378). Paired t-tests were performed to assess differences between the pre- and post- workshop RIPLS scores. Welch's t-tests were deployed to evaluate interdisciplinary differences in their scores. Qualitative analyses were conducted using an explanatory sequential design with focus group discussions (FGDs) held with 17 dental students to explain the quantitative results. RESULTS: Total RIPLS scores increased significantly for every discipline after the workshops (p < 0.001). Dental students scored significantly lower pre- and post- workshop aggregates than medical and nursing students, respectively (p < 0.001). The FGDs yielded three principal themes in the explanations tendered by dental students on their lower scores: 1) dental students rarely felt the need for interprofessional collaborations, 2) dentists often worked without the need for interprofessional collaborations, and 3) dental students believed their contribution to the workshop was insufficient. CONCLUSIONS: The results revealed divergences in the readiness of dental, medical, and nursing students for interprofessional learning, and the study illuminated possible reasons for these disparities. These outcomes will help develop evidence-based IPE by indicating approaches to place a higher value on interprofessional collaborations in educational environments, ameliorate the awareness of educators, and enhance the workshop facilitation style.

Possible roles of AMPK and macropinocytosis in the defense responses against Δ9-THC toxicity on HL-1 cardiomyocytes.

Cannabinoids are some of the most popular recreationally used illicit drugs, and are frequently consumed along with alcoholic beverages. Although the whole body effects of cannabinoids depend largely on their effects on the central nerve system, cannabinoids could harm the heart directly, due to the presence of the endocannabinoid system including cannabinoid receptor1 and 2 (CB-R1 and CB-R2) in the heart. The aim of this study is to examine the mechanism of direct cardiotoxicity of Δ9-tetrahydrocannabinol (Δ9-THC), the main psychoactive ingredient of cannabis. For this purpose, HL-1 murine atrial cardiac muscle cells were treated with 10 or 30 µM Δ9-THC, along with 100 mM ethanol to examine the possible synergistic effects of Δ9-THC and ethanol. Transcriptome analysis showed upregulation of the genes involved in the unfolded protein response (UPR), including Bip, CHOP, ATF4 and ATF6, in cells treated with Δ9-THC. Immunoblot analysis showed caspase3 activation, indicating apoptosis caused by ER stress in Δ9-THC-treated cells. Microscopic analysis showed that Δ9-THC enhances macropinocytosis, a process involved in the uptake of extracellular fluids including nutrients. Moreover Δ9-THC seemed to activate AMPK, a sensor of intracellular energy status and an activator of macropinocytosis. Finally, we found that compound C (AMPK inhibitor) aggravated cell death by Δ9-THC while AICAR (AMPK activator) ameliorated it. Collectively, these results indicate that the activation of AMPK is necessary for the survival of HL-1 cells against Δ9-THC toxicity. Macropinocytosis might serve as one of the survival pathways downstream of AMPK.

Perceived Preparedness of Dental Academic Institutions to Cope with the COVID-19 Pandemic: A Multi-Country Survey.

Dental academic institutions are affected by COVID-19. We assessed the perceived COVID-19 preparedness of these institutions and the characteristics of institutions with greater perceived preparedness. An international cross-sectional survey of dental academics was conducted from March to August 2020 to assess academics' and institutional attributes, perceived preparedness, and availability of infection prevention and control (IPC) equipment. Principal component analysis (PCA) identified perceived preparedness components. Multilevel linear regression analysis assessed the association between perceived preparedness and fixed effect factors (academics' and institutions' attributes) with countries as random effect variable. Of the 1820 dental academics from 28 countries, 78.4% worked in public institutions and 75.2% reported temporary closure. PCA showed five components: clinic apparel, measures before and after patient care, institutional policies, and availability of IPC equipment. Significantly less perceived preparedness was reported in lower-middle income (LMICs) (B = -1.31, p = 0.006) and upper-middle income (UMICs) (B = -0.98, p = 0.02) countries than in high-income countries (HICs), in teaching only (B = -0.55, p < 0.0001) and in research only (B = -1.22, p = 0.003) than teaching and research institutions and in institutions receiving ≤100 patients daily than those receiving >100 patients (B = -0.38, p < 0.0001). More perceived preparedness was reported by academics with administrative roles (B = 0.59, p < 0.0001). Academics from low-income countries (LICs) and LMICs reported less availability of clinic apparel, IPC equipment, measures before patient care, and institutional policies but more measures during patient care. There was greater perceived preparedness in HICs and institutions with greater involvement in teaching, research, and patient care.

Porphyromonas gingivalis Administration Induces Gestational Obesity, Alters Gene Expression in the Liver and Brown Adipose Tissue in Pregnant Mice, and Causes Underweight in Fetuses.

Preventing adverse pregnancy outcomes is crucial for maternal and child health. Periodontal disease is a risk factor for many systemic diseases including adverse pregnancy outcomes, such as preterm birth and low birth weight. In addition, the administration of the periodontopathic bacterium Porphyromonas gingivalis exacerbates obesity, glucose tolerance, and hepatic steatosis and alters endocrine function in the brown adipose tissue (BAT). However, the effects of having periodontal disease during pregnancy remain unclear. Thus, this study investigates the effect of P. gingivalis administration on obesity, liver, and BAT during pregnancy. Sonicated P. gingivalis (Pg) or saline (Co) was injected intravenously and administered orally to pregnant C57BL/6J mice three times per week. Maternal body weight and fetal body weight on embryonic day (ED) 18 were evaluated. Microarray analysis and qPCR in the liver and BAT and hepatic and plasma triglyceride quantification were performed on dams at ED 18. The body weight of Pg dams was heavier than that of Co dams; however, the fetal body weight was decreased in the offspring of Pg dams. Microarray analysis revealed 254 and 53 differentially expressed genes in the liver and BAT, respectively. Gene set enrichment analysis exhibited the downregulation of fatty acid metabolism gene set in the liver and estrogen response early/late gene sets in the BAT, whereas inflammatory response and IL6/JAK/STAT3 signaling gene sets were upregulated both in the liver and BAT. The downregulation of expression levels of Lpin1, Lpin2, and Lxra in the liver, which are associated with triglyceride synthesis, and a decreasing trend in hepatic triglyceride of Pg dams were observed. P. gingivalis administration may alter lipid metabolism in the liver. Overall, the intravenous and oral administration of sonicated P. gingivalis-induced obesity and modified gene expression in the liver and BAT in pregnant mice and caused fetuses to be underweight.

The Relationship between the Sense of Coherence of Dental Hygiene Students in Their Graduation Year and Their View of the Profession and Attitude to Work: A Cross-Sectional Survey in Japan.

OBJECTIVE: The need to make sense of coherence in placement support for student dental hygienists has been shown. On this basis, this study investigated the relationship between the sense of coherence of student dental hygienists and their view of the profession and attitude to work in order to clarify how they perceive their prospects for employment. METHODS: The subjects were graduation-year students at all of the dental hygienist training institutions in Japan, and anonymous, self-administered questionnaires were sent to the institutions by post in 2019. The results were analyzed by χ2 tests, as well as one-way analysis of variance and multiple comparisons using Tukey's test, with the level of significance set at 5%. RESULTS: Of 6270 questionnaires that were returned, 6264 were analyzed. The sense of coherence (SOC) component senses were manageability (F(26,221) = 5306.06, p < 0.01), meaningfulness (F(26,222) = 4373.48, p < 0.01), and comprehensibility (F(26,216) = 3986.12, p < 0.01), with meaningfulness scoring significantly higher than the other two (p < 0.01). Analysis with SOC scores divided into the low, medium, and high groups showed a relationship between the SOC of student dental hygienists and their view of the profession and attitude to work (p < 0.01), such that higher SOC scores were associated with a better view of the profession and a better attitude to work (F(26,225) = 282.18, p < 0.01). CONCLUSIONS: The results suggest that education that increases SOC in dental hygienist training programs may positively affect future prospects for student dental hygienists.

Pyroptotic cell death by exposure to 1-butanol in H9c2 cardiomyoblastoma cells.

The aim of this study is to examine the molecular mechanism of cytotoxicity caused by direct exposure to short chain alcohol. We showed previously that exposing H9c2 cardiomyoblastoma cells to 150 mM 1-butanol results in cell death within 1 h through an intrinsic apoptotic pathway. The cell death is accompanied by plasma membrane blebbing and caspase-3 activation. Here we show that a higher concentration (200 mM) of 1-butanol, as well as prolonged exposure (3-6 h) to 150 mM 1-butanol, induces plasma membrane ballooning, a characteristic feature of pyroptosis. Although gasderminD (GSDMD) cleavage by caspase-1 was not observed, GSDME cleavage by caspase-3 was observed during exposure to 150 mM 1-butanol for 6 h. We conclude that pyroptotic cell death by 1-butanol in H9c2 cardiomyoblastoma cells should occur via the caspase-3-GSDME pathway, revealing that 1-butanol could induce not only apoptosis but also pyroptosis in the cells.

Behavior change due to COVID-19 among dental academics-The theory of planned behavior: Stresses, worries, training, and pandemic severity.

OBJECTIVE: COVID-19 pandemic led to major life changes. We assessed the psychological impact of COVID-19 on dental academics globally and on changes in their behaviors. METHODS: We invited dental academics to complete a cross-sectional, online survey from March to May 2020. The survey was based on the Theory of Planned Behavior (TPB). The survey collected data on participants' stress levels (using the Impact of Event Scale), attitude (fears, and worries because of COVID-19 extracted by Principal Component Analysis (PCA), perceived control (resulting from training on public health emergencies), norms (country-level COVID-19 fatality rate), and personal and professional backgrounds. We used multilevel regression models to assess the association between the study outcome variables (frequent handwashing and avoidance of crowded places) and explanatory variables (stress, attitude, perceived control and norms). RESULTS: 1862 academics from 28 countries participated in the survey (response rate = 11.3%). Of those, 53.4% were female, 32.9% were <46 years old and 9.9% had severe stress. PCA extracted three main factors: fear of infection, worries because of professional responsibilities, and worries because of restricted mobility. These factors had significant dose-dependent association with stress and were significantly associated with more frequent handwashing by dental academics (B = 0.56, 0.33, and 0.34) and avoiding crowded places (B = 0.55, 0.30, and 0.28). Low country fatality rates were significantly associated with more handwashing (B = -2.82) and avoiding crowded places (B = -6.61). Training on public health emergencies was not significantly associated with behavior change (B = -0.01 and -0.11). CONCLUSIONS: COVID-19 had a considerable psychological impact on dental academics. There was a direct, dose-dependent association between change in behaviors and worries but no association between these changes and training on public health emergencies. More change in behaviors was associated with lower country COVID-19 fatality rates. Fears and stresses were associated with greater adoption of preventive measures against the pandemic.

Extracellular glucose is crucially involved in the fate decision of LPS-stimulated RAW264.7 murine macrophage cells.

Pyroptosis, a type of inflammatory cell death, is dependent on the inflammatory caspase-mediated cleavage of gasdermin D (GSDMD), and the subsequent pore formation on plasma membranes through which interleukin (IL)-1ß and IL-18 are released from cells. During proinflammatory activation, macrophages shift their metabolism from aerobic oxidative phosphorylation to anaerobic glycolysis. Hypoxia-inducible factor (HIF)1α is involved in the induction of IL-1ß gene expression as well as the metabolic shift towards glycolysis. However, the relationships between pyroptosis and glycolysis, as well as between pyroptosis and HIF1α are poorly investigated. Here we show that lipopolysaccharide (LPS) stimulation of RAW264.7 murine macrophage cells results in pyroptosis when cells are cultured in high glucose medium. During pyroptosis, HIF1α activation occurs transiently followed by downregulation to sub-basal levels. HIF1α downregulation and pyroptosis are observed when cells are stimulated with LPS under high glucose conditions. We also found that intracellular levels of methylglyoxal (MGO), a side product of glycolysis, increase when cells are stimulated with LPS under high glucose conditions. The addition of glycolysis inhibitor and rapamycin suppresses HIF1α downregulation and pyroptosis. These results show that glycolysis plays a crucial role not only in pro-inflammatory activation, but also in pyroptosis in LPS-stimulated RAW264.7 macrophages.

Preparation of dentin standard samples for age estimation based on increased aspartic acid racemization rate by heating.

Age estimation in adults based on aspartic acid racemization (AAR) provides fewer errors and higher precision than that based on bone morphology for the identification of cadavers. The technique has been established in some labs as a routine method. However, as the essential requisites for the technique, a wide age range of teeth of the same type as the target tooth must be collected for calibration for each examination. We investigated whether dentin standard samples could be prepared by increasing the AAR rate via heat. Powdered dentin was prepared from a maxillary first premolar (13 years) and heated for 0-72 h at 110 °C. The extent of AAR increased significantly with heating time and the correlation was strong (r = 0.913; p < 0.01). Similar results were found for a mandibular canine (24 years, r = 0.948; p < 0.01) and a maxillary third molar (20 years, r = 0.944; p < 0.01). We attempted to estimate the age of four maxillary first premolars of persons aged 25-58 years by using the heated samples (18 years, 12 h to 7 days). The differences between the actual and estimated ages were within ±5 years. The stability of the AAR rates in the powdered dentin during storage at 22-25 °C, 4 °C, and -30 °C was examined after 1 year and no significant changes had occurred. We were able to prepare dentin standard samples and created a calibration curve. This is a pilot study that needs to be validated before it can be used in forensic practice.

Formation of high molecular weight p62 by CORM-3.

CORM-3 is a water-soluble carbon monoxide (CO)-releasing molecule developed for possible therapeutic use of CO. CORM-3 belongs to a group of metal carbonyl compounds that contain transition metals and carbonyls as the central scaffold and coordinated ligands, respectively. CORM-3 has been reported to be reactive with many proteins in eukaryotes including mammals. Among them, several extracellular proteins, such as lysozyme, as well as plasma albumin and fibronectin, have been shown to interact directly with CORM-3. p62 is an intracellular adaptor protein required for targeting ubiquitinated (Ub) proteins to lysosomal degradation through autophagy. p62 has been shown to undergo self-oligomerization via covalent crosslinking in response to treatment with verteporfin, a benzoporphyrin derivative used for photodynamic therapy. Here we show that CORM-3 also interacts directly with p62. When applied to mouse embryonic fibroblasts (MEFs) at a high concentration (1 mM), CORM-3 causes the formation of reduction- and detergent-resistant high molecular weight (HMW)-p62. HMW-p62 accumulates more in atg5-/- MEFs than in wild type (WT) MEFs, showing the elimination of HMW-p62 through autophagy. HMW-p62 is also generated in H9c2 rat cardiomyoblastoma as well as A549 human alveolar epithelial cells, suggesting that HMW-p62 formation is not specific to MEFs, but, rather, is a general event in mammalian cells. HMW-p62 formation by CORM-3 can be reproduced using purified p62 in vitro, demonstrating the direct interaction between CORM-3 and p62. These results show that p62 is a CORM-3-interactive intracellular protein.

Necrosis in human neuronal cells exposed to paraquat.

Paraquat (PQ) is an herbicide that was once used worldwide, but is now prohibited in many nations due to its high toxicity to humans. However, there are still rare cases of the fetal intoxication of PQ, which was purchased prior to the prohibition in Japan. In this study, several cell death pathways, the mitochondrial stress response, and autophagy were examined in SH-SY5Y cells exposed to PQ. The results reveal the decrease of a mitochondrial stress sensitive-BNIP3 (Bcl-2/adenovirus E1B 19-kDa-interacting protein 3) protein, the suppression of autophagic flux, and the lack of apoptosis as well as other regulated forms of necrosis, such as necroptosis and ferroptosis. Taken together, our preliminary survey of cellular responses against PQ shows that, although responses of mitochondria and autophagy are observed, subsequent cell death is necrosis. Mechanism of PQ-induced SH-SY5Y cell death should be complicated and cannot be explained thoroughly by already-known mechanisms.