RhoA rescues cardiac senescence by regulating Parkin-mediated mitophagy.

Heart failure is one of the leading causes of death worldwide. RhoA, a small GTPase, governs actin dynamics in various tissue and cell types, including cardiomyocytes; however, its involvement in cardiac function has not been fully elucidated. Here, we generated cardiomyocyte-specific RhoA conditional knockout (cKO) mice, which demonstrated a significantly shorter lifespan with left ventricular dilation and severely impaired ejection fraction. We found that the cardiac tissues of the cKO mice exhibited structural disorganization with fibrosis and also exhibited enhanced senescence compared with control mice. In addition, we show that cardiomyocyte mitochondria were structurally abnormal in the aged cKO hearts. Clearance of damaged mitochondria by mitophagy was remarkably inhibited in both cKO cardiomyocytes and RhoA-knockdown HL-1 cultured cardiomyocytes. In RhoA-depleted cardiomyocytes, we reveal that the expression of Parkin, an E3 ubiquitin ligase that plays a crucial role in mitophagy, was reduced, and expression of N-Myc, a negative regulator of Parkin, was increased. We further reveal that the RhoA-Rho kinase axis induced N-Myc phosphorylation, which led to N-Myc degradation and Parkin upregulation. Re-expression of Parkin in RhoA-depleted cardiomyocytes restored mitophagy, reduced mitochondrial damage, attenuated cardiomyocyte senescence, and rescued cardiac function both in vitro and in vivo. Finally, we found that patients with idiopathic dilated cardiomyopathy without causal mutations for dilated cardiomyopathy showed reduced cardiac expression of RhoA and Parkin. These results suggest that RhoA promotes Parkin-mediated mitophagy as an indispensable mechanism contributing to cardioprotection in the aging heart.

Postmortem plasma pentraxin 3 is a useful marker of fatal acute coronary syndrome.

Pentraxin 3 (PTX3) is an acute-phase protein that belongs to the pentraxin superfamily. Recently, many clinical studies have demonstrated that plasma PTX3 concentrations rapidly increase in patients with the acute coronary syndrome (ACS). The aim of this study was to evaluate the forensic utility of postmortem plasma PTX3 as a marker of fatal ACS. We compared the plasma PTX3 concentration in cadavers with suspected fatal ACS to that exhibited in control cases (e.g., asphyxia and immediate death due to a fatal injury). The ACS groups included a coronary stenosis group, which exhibited apparent coronary stenosis, but an absence of coronary thrombi, a coronary thrombi group with thrombi found in the coronary artery, and a group of myocardial rupture following an acute myocardial infarction. The plasma PTX3 concentration was significantly higher in the coronary thrombi group than the control group and other ACS groups. The postmortem plasma PTX3 concentration was higher than the clinical reference values, which appeared to be caused by a postmortem release from circulating neutrophils. In conclusion, although the clinical reference value cannot be applied to postmortem samples, the postmortem plasma PTX3 concentration may be a useful marker of death occurring immediately after the onset of fatal ACS.

Criminal mercury vapor poisoning using heated tobacco product.

We report an unusual case of mercury vapor poisoning from using a heated tobacco product. The suspect had added grains of mercury into 20 cigarettes in a pack. When a 36-year-old Japanese man inserted one of these cigarettes into the battery powered holder, it was heated to a temperature of 350 °C, and he inhaled vaporized mercury. After using 14 of the cigarettes over 16 h, he noticed he had flu-like symptoms so he visited the hospital. Although no physical abnormalities were revealed, 99 µg/L of mercury was detected in his serum sample. His general condition improved gradually and his whole blood mercury level had decreased to 38 µg/L 5 days later. When the remaining six cigarettes in the pack were examined, many metallic grains weighing a total of 1.57 g were observed. Energy dispersive X-ray fluorescence spectrometry confirmed the grains as elemental mercury. Accordingly, the victim was diagnosed with mercury poisoning. Because the mercury was incorporated into cigarettes, an unusual and novel intoxication occurred through the heating of the tobacco product. Both medical and forensic scientific examination confirmed this event as attempted murder.

Infant fatality case with excessive chylous ascites.

An 11-month-old boy with marked abdominal distension was found dead in the prone position at home. Since there were many bruises in the non-protruding regions of the head, face, and abdomen, a medicolegal autopsy was performed the following day. The boy was smaller than average (height: 68.5 cm; weight: 7.8 kg); his extremities were thin; and his abdomen was remarkably bulging. Chylous ascites (1600 mL) was observed in the peritoneal cavity and chylous pleural effusion (left: 5 mL; right: 10 mL) in the thoracic cavity. A fibrous induration, approximately 2.0 × 1.5 cm in size, was observed in the root of the small bowel mesentery. Congenital chylothorax and chylous ascites were suspected. However, the remarkably withered thymus and an old injury in the superior labial frenulum suggested that the chylous ascites may have been further deteriorated by injuries sustained during physical abuse. Examination suggested that the death was sudden. Thus, we inferred that the cause of death was circulatory and respiratory failure due to excessive chylous ascites. Among the reported cases of chylous ascites in pediatric patients, some patients experiencing abuse were identified on the basis of their chief complaints of vomiting or abdominal distension. Medical and child welfare staff should be made aware of this information.

Comparison between Temperature Gradient Gel Electrophoresis of Bacterial 16S rDNA and Diatom Test for Diagnosis of Drowning.

When a body is discovered in water, it is difficult to conclude whether the cause of death was drowning, even today. Although diatom testing by the digestive method is classical, we hypothesized that aquatic bacteria, as well as diatoms, might be detected in drowned bodies, and conducted temperature gradient gel electrophoresis (TGGE)-targeting 16S rDNA. DNA was extracted from the site water, and from heart blood and liver samples from 27 bodies concluded as drowning deaths by autopsy and subjected to TGGE after amplification of 16S rDNA by polymerase chain reaction. We observed whether the feature point of each 16S rDNA from the site water and blood or liver samples matched. Considerably higher correspondence was observed in drowned bodies, and the rate was higher than that achieved with the digestive method. Moreover, TGGE is safer than the digestive method. Our study suggests that this method can aid diagnosis of drowning.

Still without Sales Restriction? Fatal Caffeine Toxicity A case report.

Caffeine-containing drinks are popular daily beverages worldwide and highly concentrated caffeine in the form of tablets is easily obtainable in local chemists. It is common to detect caffeine in toxicological screens in autopsy cases, but we always have to take in account that caffeine itself possesses toxicity which may sometimes lead to death The case was a 44-year-old woman who was found dead in her room one day in June. Empty packages of 'Estaron Mocha 12®, accounting for 14 tablets, were found at the scene. The autopsy showed nothing remarkable suggesting external forces, apart from white granules in her stomach. Toxicological analysis revealed 127 mg/L of caffeine concentration in the deceased's blood, which was considered to be fatal. Caffeine intoxication cases have been reported from many countries. Some are caused by accidental overtake of energy drinks, and many others are caused by intentional intake of caffeine tablets. We think that some restrictions will be effective to prevent this kind of death.