The Relationship Between Asian Dust Events and Out-of-Hospital Cardiac Arrests in Japan

Background: Asian dust events are caused by dust storms that originate in the deserts of China and Mongolia and drift across East Asia. We hypothesized that the dust events would increase incidence of out-of-hospital cardiac arrests by triggering acute events or exacerbating chronic diseases.Methods: We analyzed the Utstein-Style data collected in 2005 to 2008 from seven prefectures covering almost the entire length of Japan to investigate the effect of Asian dust events on out-of-hospital cardiac arrests. Asian dust events were defined by the measurement of light detection and ranging. A time-stratified case-crossover analysis was performed. The strength of the association between Asian dust events and out-of-hospital cardiac arrests was shown by odds ratios and 95% confidence intervals in two conditional logistic models. A pooled estimate was obtained from area-specific results by random-effect meta-analysis.Results: The total number of cases of out-of-hospital cardiac arrest was 59 273, of which 35 460 were in men and 23 813 were in women. The total number of event days during the study period was smallest in Miyagi and Niigata and largest in Shimane and Nagasaki. There was no significant relationship between Asian dust events and out-of-hospital cardiac arrests by area in either of the models. In the pooled analysis, the highest odds ratios were observed at lag day 1 in both model 1 (OR 1.07; 95% CI, 0.97?1.19) and model 2 (OR 1.08; 95% CI, 0.97?1.20). However, these results were not statistically significant.Conclusions: We found no evidence of an association between Asian dust events and out-of-hospital cardiac arrests

Uterine Carcinosarcoma in a 2-year-old Female Wistar Hannover GALAS Rat

Carcinosarcomas are rare tumors in humans as well as rats and most commonly occur in the uterus. Recently, we observed a case of incidental carcinosarcoma of the uterus in a female Wistar Hannover GALAS [BrlHan:WIST@ Jcl (GALAS)] rat at 2 years of age. Histopathologically, the tumor was characterized by an admixture of malignant epithelial and nonepithelial elements. The carcinomatous components represented a type of endometrial carcinoma, consisting of glandular and solid proliferation of large-sized tumor cells. Prominent mitoses and tumor cell invasion were observed. The sarcomatous components were characterized by multifocal proliferation of severe atypical cells with cartilage matrix and were diagnosed as chondrosarcoma. Transitions between carcinomatous and sarcomatous components were observed, and many tumor cells in the solid lesion showed immunohistochemical reactivity with both cytokeratin and vimentin. Based on these findings, this tumor was diagnosed as a uterine carcinosarcoma. This is the first report of uterine carcinosarcoma in Wistar Hannover GALAS [BrlHan:WIST@Jcl (GALAS)] rats

Lithium and strontium isotopic systematics of waters around Ontake volcano, Japan: Implications for deep-seated fluids and earthquake swarms

Since 1976, earthquake swarms have occurred beneath the southeast flank of Ontake volcano in central Japan. Electrical conductivity surveys have shown that these earthquake swarms are associated with the upwelling of deep-seated fluid. To investigate the nature of the deep-seated fluid, we analyzed 7Li/6Li and 87Sr/86Sr ratios of water samples collected from springs and wells around Ontake volcano in 2000, 2003, 2005, 2007, and 2009. The Li and Sr isotopic compositions of these water samples are largely explained by binary component mixing between near-surface meteoric water and non-surface fluid at each sampling site. On the basis of their Cl/Li and Cl/Sr ratios, we singled out water samples whose Li and Sr isotopic ratios were minimally affected by meteoric water contamination to represent non-surface fluids. The Li and Sr isotopic compositions of most Ontake non-surface fluids, except for samples from the earthquake swarm region, can be explained as the result of volcanic fluids reacting with basement rocks, where they acquired upper crustal signatures. We attribute the fluid associated with the region of earthquake swarms to the lower crust beneath the study area

Activating transcription factor-4 promotes mineralization in vascular smooth muscle cells

Emerging evidence indicates that upregulation of the ER stress–induced pro-osteogenic transcription factor ATF4 plays an important role in vascular calcification, a common complication in patients with aging, diabetes, and chronic kidney disease (CKD). In this study, we demonstrated the pathophysiological role of ATF4 in vascular calcification using global Atf4 KO, smooth muscle cell–specific (SMC-specific) Atf4 KO, and transgenic (TG) mouse models. Reduced expression of ATF4 in global ATF4-haplodeficient and SMC-specific Atf4 KO mice reduced medial and atherosclerotic calcification under normal kidney and CKD conditions. In contrast, increased expression of ATF4 in SMC-specific Atf4 TG mice caused severe medial and atherosclerotic calcification. We further demonstrated that ATF4 transcriptionally upregulates the expression of type III sodium-dependent phosphate cotransporters (PiT1 and PiT2) by interacting with C/EBPβ. These results demonstrate that the ER stress effector ATF4 plays a critical role in the pathogenesis of vascular calcification through increased phosphate uptake in vascular SMCs

Anti-NF-κB peptide derived from nuclear acidic protein attenuates ovariectomyinduced osteoporosis in mice

NF-κB is a transcription factor that is activated with aging. It plays a key role in the development of osteoporosis by promoting osteoclast differentiation and inhibiting osteoblast differentiation. In this study, we developed a small anti-NF-κB peptide called 6A-8R from a nuclear acidic protein (also known as macromolecular translocation inhibitor II, Zn2+-binding protein, or parathymosin) that inhibits transcriptional activity of NF-κB without altering its nuclear translocation and binding to DNA. Intraperitoneal injection of 6A-8R attenuated ovariectomy-induced osteoporosis in mice by inhibiting osteoclast differentiation, promoting osteoblast differentiation, and inhibiting sclerostin production by osteocytes in vivo with no apparent side effects. Conversely, in vitro, 6A-8R inhibited osteoclast differentiation by inhibiting NF-κB transcriptional activity, promoted osteoblast differentiation by promoting Smad1 phosphorylation, and inhibited sclerostin expression in osteocytes by inhibiting myocyte enhancer factors 2C and 2D. These findings suggest that 6A-8R has the potential to be an antiosteoporotic therapeutic agent with uncoupling properties.Takami K., Okamoto K., Etani Y., et al. Anti-NF-κB peptide derived from nuclear acidic protein attenuates ovariectomyinduced osteoporosis in mice. JCI Insight 8, e171962 (2023); https://doi.org/10.1172/jci.insight.171962

Basic fibroblast growth factor promotes meniscus regeneration through the cultivation of synovial mesenchymal stem cells via the CXCL6–CXCR2 pathway

Objective: To investigate the efficacy of basic fibroblast growth factor (bFGF) in promoting meniscus regeneration by cultivating synovial mesenchymal stem cells (SMSCs) and to validate the underlying mechanisms. Methods: Human SMSCs were collected from patients with osteoarthritis. Eight-week-old nude rats underwent hemi-meniscectomy, and SMSCs in pellet form, either with or without bFGF (1.0 × 106 cells per pellet), were implanted at the site of meniscus defects. Rats were divided into the control (no transplantation), FGF (−) (pellet without bFGF), and FGF (+) (pellet with bFGF) groups. Different examinations, including assessment of the regenerated meniscus area, histological scoring of the regenerated meniscus and cartilage, meniscus indentation test, and immunohistochemistry analysis, were performed at 4 and 8 weeks after surgery. Results: Transplanted SMSCs adhered to the regenerative meniscus. Compared with the control group, the FGF (+) group had larger regenerated meniscus areas, superior histological scores of the meniscus and cartilage, and better meniscus mechanical properties. RNA sequencing of SMSCs revealed that the gene expression of chemokines that bind to CXCR2 was upregulated by bFGF. Furthermore, conditioned medium derived from SMSCs cultivated with bFGF exhibited enhanced cell migration, proliferation, and chondrogenic differentiation, which were specifically inhibited by CXCR2 or CXCL6 inhibitors. Conclusion: SMSCs cultured with bFGF promoted the expression of CXCL6. This mechanism may enhance cell migration, proliferation, and chondrogenic differentiation, thereby resulting in superior meniscus regeneration and cartilage preservation.Goshima A., Etani Y., Hirao M., et al. Basic fibroblast growth factor promotes meniscus regeneration through the cultivation of synovial mesenchymal stem cells via the CXCL6–CXCR2 pathway. Osteoarthritis and Cartilage , (2023); https://doi.org/10.1016/j.joca.2023.07.010

Two Distinct Mechanisms Underlying γδ T Cell-Mediated Regulation of Collagen Type I in Lung Fibroblasts

Idiopathic pulmonary fibrosis is a chronic intractable lung disease, leading to　respiratory failure and death. Although anti-fibrotic agents delay disease progression, they are not considered curative treatments, and alternative modalities have attracted attention. We examined the effect of human γδ T cells on collagen type I in lung fibroblasts. Collagen type I was markedly reduced in a γδ T cell number-dependent manner following treatment with γδ T cells expanded with tetrakis-pivaloxymethyl 2-(thiazole-2-ylamino) ethylidene-1,1-bisphosphonate (PTA) and interleukin-2. Collagen type I levels remained unchanged on addition of γδ T cells to the culture system through a trans-well culture membrane, suggesting that cell–cell contact is essential for reducing its levels in lung fibroblasts. Re-stimulating γδ T cells with (E)-4-hydroxy-3-methylbut-2-enyl diphosphate (HMBPP) reduced collagen type I levels without cell–cell contact, indicating the existence of HMBPP-induced soluble anti-fibrotic factors in γδ T cells. Adding anti-interferon-γ (IFN-γ)-neutralizing mAb restored collagen type I levels, demonstrating that human γδ T cell-derived IFN-γ reduces collagen type I levels. Conversely, interleukin-18 augmented γδ T cell-induced suppression of collagen type I. Therefore, human γδ T cells reduce collagen levels in lung fibroblasts via two distinct mechanisms; adoptive γδ T cell transfer is potentially a new therapeutic candidate

Local expression of Toll-like receptor 4 at the site of ruptured plaques in patients with acute myocardial infarction

Several reports suggest that a chronic inflammatory process plays a key role in coronary artery plaque instability and subsequent occlusive thrombosis. In a previous study, we found that TLR4 (Toll-like receptor 4) mediates the synthesis of cytokines in circulating monocytes of patients with AMI (acute myocardial infarction); however, it remains unclear whether TLRs are expressed at the site of the ruptured plaque in these patients. The aim of the present study was to determine whether TLR2 and TLR4 are expressed at the site of ruptured plaques in patients with AMI and to compare this with systemic levels. The study included 62 patients with AMI, 20 patients with SA (stable angina) and 32 subjects with a normal coronary angiogram (control). Local samples from the site of the ruptured plaque were taken from patients with AMI using aspiration catheterization. Systemic blood samples from the aorta were taken from patients with AMI and SA and controls. Systemic levels of TLR2 and TLR4 were higher in patients with AMI than in patients with SA and controls. In patients with AMI, local TLR4 levels were higher than systemic levels. There was no significant difference in TLR2 levels between local and systemic samples. TLR4 immunostaining was positive in infiltrating macrophages in ruptured plaque material. Cardiac events were observed in 16 patients with AMI at the time of the 6-month follow-up study. Local and systemic levels of TLR4 were higher in patients with AMI with cardiac events than in those without. These results indicate an increase in monocytic TLR4 expression not only in the systemic circulation, but also at the site of plaque rupture. In conclusion, expression of both systemic and local plaque TLR4 may be one of the mechanisms responsible for the pathogenesis of AMI

A patient with esophageal hemangioma treated by endoscopic mucosal resection : a case report and review of the literature

In a 58-year-old male, upper digestive endoscopy revealed a protruding lesion in the esophagus on a medical examination. The patient was referred to the Department of Surgery in our hospital to undergo surgery. On the initial consultation, upper digestive endoscopy showed a smooth, soft, black purple, typeⅡprotruding lesion measuring approximately 25mmat 35 cm apart from the incisor. For diagnotic treatment and patient’s request, endoscopic mucosal resection (EMR)was performed. The resected specimen measured 25mm× 25 mm. The histological findings suggested cavernous hemangioma. To treat esophageal hemangioma, esohagectomy, tumor enucleation, or sclerotherapy has been performed. However, recently, thorough preoperative examination, such as endoscopic ultrasonography (EUS), has facilitated endoscopic resection, such as EMR