Background: Aristolochic acid nephropathy (AAN) is a rapidly progressive interstitial nephropathy caused by Aristolochic acid (AA). AAN is associated with the development of nephropathy and urothelial carcinoma. It is estimated that more than 100 million people worldwide are at risk of developing AAN. However, the underlying mechanisms driving renal deterioration in AAN remain poorly understood, and the treatment options are limited.
Methods: We obtained GSE27168 and GSE136276 series matrix data from the Gene Expression Omnibus (GEO) related to AAN. Using the R Studio environment, we applied the limma package and WGCNA package to identify co-differently expressed genes (co-DEGs). By GO/KEGG/GSVA analysis, we revealed common biological pathways. Subsequently, co-DEGs were subjected to the String database to construct a protein-protein interaction (PPI) network. The MCC algorithms implemented in the Cytohubba plugin were employed to identify hub genes. The hub genes were cross-referenced with the transcription factor (TF) database to identify hub TFs. Immune infiltration analysis was performed to identify key immune cell groups by utilizing CIBERSORT. The expressions of AAN-associated hub TFs were verified in vivo and in vitro. Finally, siRNA intervention was performed on the two TFs to verify their regulatory effect in AAN.
Results: Our analysis identified 88 co-DEGs through the “limma” and “WGCNA” R packages. A PPI network comprising 53 nodes and 34 edges was constructed with a confidence level >0.4. ATF3 and c-JUN were identified as hub TFs potentially linked to AAN. Additionally, expressions of ATF3 and c-JUN positively correlated with monocytes, basophils, and vessels, and negatively correlated with eosinophils and endothelial cells. We observed a significant increase in protein and mRNA levels of these two hub TFs. Furthermore, it was found that siRNA intervention targeting ATF3, but not c-JUN, alleviated cell damage induced by AA. The knockdown of ATF3 protects against oxidative stress and inflammation in the AAN cell model.
Conclusion: This study provides novel insights into the role of ATF3 in AAN. The comprehensive analysis sheds light on the molecular mechanisms and identifies potential biomarkers and drug targets for AAN treatment.
Background: To enhance tobacco control in Japan, the government set a future smoking rate target (smoking prevalence = 12% by 2022) arguing that the “smoking rate target is expected if only smokers who want to quit smoking now, actually quit”. However, ideally both those wanting to quit now and those who wanted to in the past will succeed in the future. We aimed to re-define smokers who intend to quit and estimate their number. We also examined determinants of intention to quit, including daily tobacco consumption and tobacco use categories (exclusive combustible cigarette users, exclusive heated tobacco product (HTP) users, and dual (combustible cigarette and HTP)) users.
Methods: Using data from the 2021 Japan ‘Society and New Tobacco’ Internet Survey, we analyzed 5,072 current smokers (had used combustible cigarettes or HTPs in the past 30 days) aged 20–80 years. Smokers who intend to quit were defined as total smokers who want to quit now, have previously attempted or previously wanted to quit. Log-Poisson regression models were used to calculate adjusted odds ratios (aORs) with 95% confidence intervals (95%CI) for intention to quit (current or current/past), adjusting for potential covariates such as tobacco use categories.
Results: Among current smokers, 40.6% want to quit now, 27.0% have previously attempted and 9.0% have previously wanted to quit. Smokers of over 20 tobacco sticks/day are less likely to want to quit now than 1–10 /day (aOR = 0.79, 95%CI = 0.71–0.87) and less likely to intend to quit (both current and past) (aOR = 0.93, 95%CI = 0.88–0.98). Exclusive HTP and dual users were more likely to intend to quit (both current and past) than exclusive combustible cigarette users (aOR = 1.09, 95%CI = 1.04–1.14) and (aOR = 1.07, 95%CI = 1.03–1.12).
Conclusions: In total, 76.6% of current smokers, were defined as having intention to quit (both current and past). Applying this percentage to the target calculation, Japan’s smoking rate target would be 3.9%, considerably lower than the current target of 12%. The Japanese government may have to revise the smoking rate target. Additionally, we found that the usage of HTPs reduces intention to quit smoking. These insights have implications for setting of smoking rate targets and regulating HTPs in different countries.
Background: Stair climbing is a readily available form of physical activity with potential cardiovascular benefits. This study aimed to investigate the association between stair climbing and numerous modifiable cardiovascular disease (CVD) risk factors.
Methods: In this cross-sectional study, we used data from 7282 Japanese people (30–84 years) residing in Suita City, Osaka. CVD risk factors and stair climbing frequency were assessed during the Suita Study health examination. Logistic regressions were used to calculate the odds ratios (ORs) and 95% confidence intervals (95% CIs) for CVD risk factors across stair climbing frequencies.
Results: After adjustment for age, sex, lifestyle, and medical conditions, stair climbing >60% of the time, compared to <20% of the time, was inversely associated with obesity, smoking, physical inactivity, and stress: ORs (95% CIs) = 0.63 (0.53, 0.75), 0.81 (0.69, 0.96), 0.48 (0.41, 0.55), and 0.67 (0.58, 0.78), respectively (p-trends < 0.05).
Conclusion: Stair climbing was inversely associated with obesity, smoking, physical inactivity, and stress; suggesting a potential role for cardiovascular disease prevention.
Background: Perfluorooctanoic acid (PFOA) is one of the major per- and polyfluoroalkyl substances. The role of ATP-binding cassette (ABC) transporters in PFOA toxicokinetics is unknown.
Methods: In this study, two ABC transporters, ABCB1 and ABCB4, were examined in mice with single intravenous PFOA administration (3.13 µmol/kg). To identify candidate renal PFOA transporters, we used a microarray approach to evaluate changes in gene expression of various kidney transporters in Abcb4 null mice.
Results: Biliary PFOA concentrations were lower in Abcb4 null mice (mean ± standard deviation: 0.25 ± 0.12 µg/mL) than in wild-type mice (0.87 ± 0.02 µg/mL). Immunohistochemically, ABCB4 expression was confirmed at the apical region of hepatocytes. However, renal clearance of PFOA was higher in Abcb4 null mice than in wild-type mice. Among 642 solute carrier and ABC transporters, 5 transporters showed significant differences in expression between wild-type and Abcb4 null mice. These candidates included two major xenobiotic transporters, multidrug resistance 1 (Abcb1) and organic anion transporter 3 (Slc22a8). Abcb1 mRNA levels were higher in Abcb4 null mice than in wild-type mice in kidney. In Abcb4 null mice, Abcb1b expression was enhanced in proximal tubules immunohistochemically, while that of Slc22a8 was not. Finally, in Abcb1a/b null mice, there was a significant decrease in the renal clearance of PFOA (0.69 ± 0.21 vs 1.1 mL ± 0.37/72 h in wild-type mice). A homology search of ABCB1 showed that several amino acids are mutated in humans compared with those in rodents and monkeys.
Conclusions: These findings suggest that, in the mouse, Abcb4 and Abcb1 are excretory transporters of PFOA into bile and urine, respectively.
Background: Non-optimum temperatures are associated with increased risk of respiratory diseases, but the effects of apparent temperature (AT) on respiratory diseases remain to be investigated.
Methods: Using daily data from 2016 to 2020 in Ganzhou, a large city in southern China, we analyzed the impact of AT on outpatient and inpatient visits for respiratory diseases. We considered total respiratory diseases and five subtypes (influenza and pneumonia, upper respiratory tract infection (URTI), lower respiratory tract infection (LRTI), asthma and chronic obstructive pulmonary disease [COPD]). Our analysis employed a distributed lag nonlinear model (DLNM) combined with a generalized additive model (GAM).
Results: We recorded 94,952 outpatients and 72,410 inpatients for respiratory diseases. We found AT significantly non-linearly associated with daily outpatient and inpatient visits for total respiratory diseases, influenza and pneumonia, and URTI, primarily during comfortable AT levels, while it was exclusively related with daily inpatient visits for LRTI and COPD. Moderate heat (32.1 °C, the 75.0th centile) was observed with a significant effect on both daily outpatient and inpatient visits for total respiratory diseases at a relative risk of 1.561 (1.161, 2.098) and 1.276 (1.027, 1.585), respectively (both P < 0.05), while the results of inpatients became insignificant with the adjustment for CO and O3. The attributable fractions in outpatients and inpatients were as follows: total respiratory diseases (24.43% and 18.69%), influenza and pneumonia (31.54% and 17.33%), URTI (23.03% and 32.91%), LRTI (37.49% and 30.00%), asthma (9.83% and 3.39%), and COPD (30.67% and 10.65%). Stratified analyses showed that children ≤5 years old were more susceptible to moderate heat than older participants.
Conclusions: In conclusion, our results indicated moderate heat increase the risk of daily outpatient and inpatient visits for respiratory diseases, especially among children under the age of 5.
Asian flush is a potential protective factor against COVID-19: a web-based retrospective survey in Japan
Released on J-STAGE: March 09, 2024 | Volume 29 Pages 14
Satoshi Takashima, Mikiko Tokiya, Katsura Izui, Hiroshi Miyamoto, Akiko Matsumoto
Effects of forest environment (Shinrin-yoku/Forest bathing) on health promotion and disease prevention —the Establishment of “Forest Medicine”—
Released on J-STAGE: November 01, 2022 | Volume 27 Pages 43
Qing Li
Maternal diabetes and risk of offspring congenital heart diseases: the Japan Environment and Children’s Study
Released on J-STAGE: April 05, 2024 | Volume 29 Pages 23
Maiko Nagasawa, Satoyo Ikehara, Yuri Aochi, Kanami Tanigawa, Tetsuhisa Kitamura, Tomotaka Sobue, Hiroyasu Iso, the Japan Environment and Children’s Study (JECS) Group
A population-based urinary and plasma metabolomics study of environmental exposure to cadmium
Released on J-STAGE: March 30, 2024 | Volume 29 Pages 22
Yoshiki Ishibashi, Sei Harada, Yoko Eitaki, Ayako Kurihara, Suzuka Kato, Kazuyo Kuwabara, Miho Iida, Aya Hirata, Mizuki Sata, Minako Matsumoto, Takuma Shibuki, Tomonori Okamura, Daisuke Sugiyama, Asako Sato, Kaori Amano, Akiyoshi Hirayama, Masahiro Sugimoto, Tomoyoshi Soga, Masaru Tomita, Toru Takebayashi
COVID-19 fatality and DALYs, and associated metabolic disorders and ambient air pollutants in pre-Omicron era of the pandemic: an international comparative study
Released on J-STAGE: April 09, 2024 | Volume 29 Pages 24
Nlandu-Roger Ngatu, Daniel-Kuezina Tonduangu, Emmanuel Munyeshyaka, Tomohiro Hirao, Georges-Matondo Balenda, Yusuke Yamadori, Takayuki Deguchi, Berthier Nsadi-Fwene, Jose-Nzunzu Lami, Steeve Akumwami, Kanae Kanda, Akitsu Murakami, Marie-Claire Yandju, Dieudonne-Tshipukane Nyembue, Antoine Tshimpi, Stanislas-Okitotsho Wembonyama