RÉSUMÉ
Cisplatin is an effective chemotherapeutic agent widely used for the treatment of various solid tumors. However, cisplatin has an important limitation in its use; currently, there is no method to ameliorate cisplatin-induced acute kidney injury (AKI). Thrombomodulin (TM) is well known not only for its role as a cofactor in the clinically important natural anticoagulation pathway but also for its anti-inflammatory properties. Here, we investigated the effects of TM in cisplatin-induced AKI. In mice intraperitoneally injected with 15 mg/kg cisplatin, TM (10 mg/kg) or PBS was administered intravenously at 24 h after cisplatin injection. TM significantly attenuated cisplatin-induced nephrotoxicity with the suppressed elevation of blood urea nitrogen and serum creatinine, and reduced histological damages. Actually, TM treatment significantly alleviated oxidative stress-induced apoptosis by reducing reactive oxygen species (ROS) levels in cisplatin-treated renal proximal tubular epithelial cells (RPTECs) in vitro. Furthermore, TM clarified cisplatin-induced apoptosis by reducing caspase-3 levels. In addition, TM attenuated the endoplasmic reticulum (ER) stress signaling pathway in both renal tissues and RPTECs to protect the kidneys from cisplatin-induced AKI. These findings suggest that TM is a potential protectant against cisplatin-induced nephrotoxicity through suppressing ROS generation and ER stress in response to cisplatin.
Sujet(s)
Atteinte rénale aigüe , Apoptose , Cisplatine , Stress du réticulum endoplasmique , Stress oxydatif , Espèces réactives de l'oxygène , Thrombomoduline , Cisplatine/effets indésirables , Animaux , Thrombomoduline/métabolisme , Stress du réticulum endoplasmique/effets des médicaments et des substances chimiques , Stress oxydatif/effets des médicaments et des substances chimiques , Atteinte rénale aigüe/induit chimiquement , Atteinte rénale aigüe/métabolisme , Atteinte rénale aigüe/traitement médicamenteux , Atteinte rénale aigüe/anatomopathologie , Souris , Espèces réactives de l'oxygène/métabolisme , Mâle , Apoptose/effets des médicaments et des substances chimiques , Rein/effets des médicaments et des substances chimiques , Rein/métabolisme , Rein/anatomopathologie , Antinéoplasiques/effets indésirables , Antinéoplasiques/toxicité , Souris de lignée C57BL , Azote uréique sanguin , Transduction du signal/effets des médicaments et des substances chimiques , Tubules contournés proximaux/effets des médicaments et des substances chimiques , Tubules contournés proximaux/métabolisme , Tubules contournés proximaux/anatomopathologieRÉSUMÉ
Matrix metalloproteinase-9 (MMP-9) is involved in tissue remodeling and in skin wound healing. The present study focuses on the MMP-9 expression in epidermal wound healing within 1 h after injury, to test whether MMP-9 can be used to estimate the time of injury in forensic practice.A sample consisting of 5 individuals undergoing surgery was analyzed. With the consent of the patients, sections of skin were removed from the surgical wound at predefined time intervals. For each subject, 8 sections were taken, one for each time interval defined at 0 '- 1' - 3 '- 5' - 10 '- 15' - 30 '- 60' minutes. The specimens were immunostained with MMP-9, and the number of positively stained cells was examined.The number of positively stained cells showed an increasing trend as a function of time. Less than 30 positively stained cells were found in all cases within 3 min. At the post-infliction time of 5 min, the number of positively stained cells exceeded 30 in 3 out of 5 cases. The number of MMP-positive cells exceeded 40 in all cases in over 10 min.In the light of these results, the count of MMP-9 positive cells might be a useful marker in the wound-age estimation within 1 h in forensic setting. More research is required to collect more samples and to compare samples from the hyperacute phase with those from several days after injury.
Sujet(s)
Immunohistochimie , Matrix metalloproteinase 9 , Cicatrisation de plaie , Humains , Matrix metalloproteinase 9/métabolisme , Projets pilotes , Mâle , Peau/traumatismes , Peau/anatomopathologie , Peau/métabolisme , Facteurs temps , Adulte d'âge moyen , Anatomopathologie légale , Adulte , Femelle , Marqueurs biologiques/métabolisme , Marqueurs biologiques/analyse , Sujet âgéRÉSUMÉ
Immunohistochemical analysis of platelet-derived growth factor receptor-α (PDGFR-α) was performed on human skin wounds obtained from forensic autopsy cases. Thirty human skin wounds were collected at different post-infliction intervals as follows: Group I, 4 h to 3 days (n = 16); Group II, 4 to 7 days (n = 7); Group III, 9 to 10 days (n = 3); and Group IV, 14 to 20 days (n = 4). Immunopositive reactions for PDGFR-α were not observed in the uninjured human skin specimens. In a semi-quantitative morphometrical analysis, the number of PDGFR-α-positive cells was observed increased in Group II, with the average number of PDGFR-α-positive cells being the highest in Group II. Additionally, in Group II, all specimens showed PDGFR-α-positive cells, with an average number of > 200 cells in five fields of view, suggesting a wound age of 4 to 7 days. Taken together, the immunohistochemical detection of PDGFR-α in human skin wounds can be a useful tool for wound age determination.
Sujet(s)
Immunohistochimie , Récepteur au PDGF alpha , Peau , Humains , Récepteur au PDGF alpha/métabolisme , Peau/traumatismes , Peau/anatomopathologie , Peau/métabolisme , Peau/composition chimique , Mâle , Femelle , Adulte d'âge moyen , Adulte , Anatomopathologie légale , Facteurs temps , Sujet âgé , Sujet âgé de 80 ans ou plusRÉSUMÉ
When exposed to oxidative and electrophilic stress, a protective antioxidant response is initiated by nuclear factor erythroid 2-related factor 2 (Nrf2). However, the extent of its importance in the forensic diagnosis of acute ischemic heart diseases (AIHD), such as myocardial infarction (MI), remains uncertain. On the other hand, immunohistochemical analyses of fibronectin (FN) and the terminal complement complex (C5b-9) prove valuable in identifying myocardial ischemia that precedes necrosis during the postmortem diagnosis of sudden cardiac death (SCD). In this study, we investigated the immunohistochemical levels of Nrf2, FN, and C5b-9 in human cardiac samples to explore their forensic relevance for the identification of acute cardiac ischemia. Heart samples were obtained from 25 AIHD cases and 39 non-AIHD cases as controls. Nrf2 was localized in the nuclei of cardiomyocytes, while FN and C5b-9 were detected in the myocardial cytoplasm. The number of intranuclear Nrf2 positive signals in cardiomyocytes increased in AIHD cases compared to control cases. Additionally, the grading of positive portions of cardiac FN and C5b-9 in the myocardium was also significantly enhanced in AIHD, compared to controls. Collectively, these results indicate that the immunohistochemical investigation of Nrf2 combined with FN, and/or C5b-9 holds the potential for identifying early-stage myocardial ischemic lesions in cases of SCD.
Sujet(s)
Infarctus du myocarde , Ischémie myocardique , Facteur-2 apparenté à NF-E2 , Humains , Complexe d'attaque membranaire du complément/métabolisme , Mort subite cardiaque/anatomopathologie , Infarctus du myocarde/anatomopathologie , Ischémie myocardique/métabolisme , Myocarde/métabolisme , Facteur-2 apparenté à NF-E2/métabolismeRÉSUMÉ
We report a case of hemoperitoneum after percutaneous radiofrequency ablation in a patient with hepatocellular carcinoma. A 60-year-old female was hospitalized for the treatment of thrombasthenia and cirrhosis caused by chronic Hepatitis C, and computed tomography revealed hepatocellular carcinoma, which was treated by percutaneous radiofrequency ablation. After the ablation, hemoperitoneum was suspected because of the low hemoglobin level with abdominal pain. Approximately 6 h after the ablation treatment, the patient suddenly fell into a shock state and died. In this case, medical treatment-related death including malpractice was suspected, and forensic autopsy was performed. The abdominal cavity contained 910 mL of dark red fluid blood and 210 g of soft hemocoagula. Moreover, several puncture marks were observed on the liver surface and diaphragm, and there was no clear damage to the main arteries and veins. Considering the macroscopic and microscopic findings, the cause of death was assumed as hemorrhagic shock due to the hemoperitoneum caused by the damage to the liver by radiofrequency ablation. It is important to consider all the indications and adverse effects of radiofrequency ablation.
Sujet(s)
Carcinome hépatocellulaire , Ablation par cathéter , Tumeurs du foie , Ablation par radiofréquence , Femelle , Humains , Adulte d'âge moyen , Carcinome hépatocellulaire/chirurgie , Carcinome hépatocellulaire/anatomopathologie , Tumeurs du foie/chirurgie , Tumeurs du foie/anatomopathologie , Hémopéritoine/étiologie , Ablation par cathéter/effets indésirables , Ablation par cathéter/méthodes , Ablation par radiofréquence/effets indésirablesRÉSUMÉ
A shared definition of femicide would help to distinguish it from the murder of a woman and understand its root causes favoring prevention. We conducted a Systematic Literature Review (SLR) to assess how (and if) femicide cases were related to mental disorders. Articles papers that explicitly define or discuss femicides or articles that, albeit not expressly mention femicides, thoroughly compare generic homicides and homicides with female victims. We analyse 3546 articles were retrieved from the databases, and 75 studies fulfilled the eligibility criteria and were included in the SLR. Many forms of femicide emerge worldwide as people's values, beliefs, attitudes, and behaviours evolve (intimate partner femicide, femicide-suicide, religious femicide, honour, revolt femicide) and state of vulnerability. A tiny percentage of femicides occur at the hands of subjects with diagnosed mental disorders, and controversies exist regarding the possible link between femicide and the use of drugs and/or alcohol and other factors. The complex problem of violence against women must be addressed with a transdisciplinary approach and targeted interventions for both the victims and the perpetrators. The present SLR shows that it is not possible to link femicides to mental disorders and that socio and cultural factors appear to be more relevant. Further quantitative research is warranted to disentangle the root causes of this heinous phenomenon plaguing our times. Our studies show that using the proposed definition of feminicide would help to delimit and adequately recognise violence in courtrooms, promote the culture of equality, and identify adequate policy strategies for prevention.
Sujet(s)
Troubles liés à une substance , Suicide , Humains , Femelle , Santé mentale , Homicide , ViolenceRÉSUMÉ
Japanese spotted fever (JSF) is potentially fatal infection transmitted by tick bites which vectors Rickettsia (R.) japonica. Since JSF was first described in 1984, the incidence has gradually been increased. We experienced a case of JSF of fatal outcome. A female in 70's was found dead on her bed, whose house was so called 'hoarding house' filled with many waists and unused items. The following day, the autopsy was performed. As representative symptom of external findings, skin rashes were seen on the trunk and extremities, and there were tick-bite eschars on the left upper arm. Internal findings showed no specific findings in each organ. Histopathological examination demonstrated massive inflammatory cell infiltrates mainly consisted of neutrophils in the dermis beneath the external eschar. Furthermore, destruction of glomeruli in kidney with microhemorrhage from mesangial regions was observed. The numerous inflammatory infiltrates were also observed in pulmonary interstitium, which were accompanied with histopathologic features of vasculitis. Biochemical examination showed severe systemic inflammation as monitored by elevated CRP of 16â¯mg/dL and renal dysfunction by BUN of 171.2â¯mg/dL and creatinine of 6.07â¯mg/dL. Subsequently polymerase chain reaction revealed specifically amplified signals for R. japonica from the samples of tick-bites eschar and blood. Thus, we diagnosed her cause of death as JSF which had been occurred multiorgan failure such as acute renal failure and possibly acute respiratory failure. (224 terms).
Sujet(s)
Rickettsia , Rickettsiose du groupe des fièvres boutonneuses , Humains , Femelle , Rickettsiose du groupe des fièvres boutonneuses/diagnostic , Rickettsiose du groupe des fièvres boutonneuses/épidémiologie , Réaction de polymérisation en chaîne , AutopsieRÉSUMÉ
Heat shock proteins (HSPs) are molecular chaperones whose primary function is cytoprotection, supporting cell survival under (sub) lethal conditions. They have been implicated in various diseases such as inflammatory diseases and cancer due to their cytoprotective and immunomodulatory effects, and their biological mechanisms have been studied. Central family members include, HSP27, which is induced by various stimuli such as heat shock, hypoxia, hyperoxia, ultraviolet exposure, and nutritional deficiency, and HSP70, which is homeostatically expressed in many organs such as the gastrointestinal tract and has anti-cell death and anti-inflammatory effects. In this study, HSP27 and HSP70 were investigated during thrombus formation and dissolution in a deep vein thrombosis model by immunohistochemistry to determine their involvement in this process and whether their expression could be used as a forensic marker. In the process of thrombus formation and lysis, HSP27 and HSP70 were found to be expressed by immunohistochemical analysis. The role of inhibitors of HSP27 and HSP70 in the pathogenesis of thrombosis in mice was also investigated. When HSP27 or HSP70 inhibitors were administered, thrombi were significantly smaller than in the control group on day 5 after inferior vena cava ligation, indicating pro-thrombotic effects HSP27 and HSP70. If HSP27- or HSP70-positive cells were clearly visible and easily identifiable in the thrombus sections, the thrombus was presumed to be more than 10 days old. Thus, the detection of intrathrombotic HSP27 and HSP70 could forensically provide useful information for the estimation of thrombus ages. Collectively, our study implied that both HSP27 and HSP70 might be molecular targets for thrombus therapy and that the detection of HSP-related molecules such as HSP27 and HSP70 could be useful for the determination of thrombus ages.
Sujet(s)
Protéines du choc thermique HSP27 , Protéines du choc thermique HSP70 , Thrombose , Thrombose veineuse , Animaux , Souris , Modèles animaux de maladie humaine , Protéines du choc thermique HSP27/métabolisme , Protéines du choc thermique HSP70/métabolisme , Thrombose veineuse/anatomopathologieRÉSUMÉ
Microsatellite instability (MSI) is a key marker to predict response to immune checkpoint inhibitors; however, only 1-2% of biliary cancers have this genomic feature. In a patient with hilar biliary cancer, MSI was examined in two cancer specimens (forceps biopsy from the biliary stricture and endoscopic ultrasound-guided fine-needle aspiration biopsy [EUS-FNAB] from the adjacent lymph node). We observed discordant results, as high frequency of MSI was found only in the forceps biopsy. Although the FNAB sample was 10 times larger than that of the forceps biopsy, the tumor concentration was much lower, which is a possible reason for the discordance. Besides, immunohistochemistry of four mismatch-repair (MMR) proteins showed proficient MMR expressions. The tumor became refractory to gemcitabine, cisplatin, and S-1 but responded well to pembrolizumab. Caution is needed for sample selection and for interpretation of the test's results, to avoid missing rare chance for effective molecular target agents.
Sujet(s)
Tumeurs des voies biliaires , Cholestase , Humains , Instabilité des microsatellites , Tumeurs des voies biliaires/traitement médicamenteux , Tumeurs des voies biliaires/génétique , Anticorps monoclonaux humanisés/usage thérapeutiqueRÉSUMÉ
Intense neutrophil infiltration into the liver is a characteristic of acetaminophen-induced acute liver injury. Neutrophil elastase is released by neutrophils during inflammation. To elucidate the involvement of neutrophil elastase in acetaminophen-induced liver injury, we investigated the efficacy of a potent and specific neutrophil elastase inhibitor, sivelestat, in mice with acetaminophen-induced acute liver injury. Intraperitoneal administration of 750 mg/kg of acetaminophen caused severe liver damage, such as elevated serum transaminase levels, centrilobular hepatic necrosis, and neutrophil infiltration, with approximately 50% mortality in BALB/c mice within 48 h of administration. However, in mice treated with sivelestat 30 min after the acetaminophen challenge, all mice survived, with reduced serum transaminase elevation and diminished hepatic necrosis. In addition, mice treated with sivelestat had reduced NOS-II expression and hepatic neutrophil infiltration after the acetaminophen challenge. Furthermore, treatment with sivelestat at 3 h after the acetaminophen challenge significantly improved survival. These findings indicate a new clinical application for sivelestat in the treatment of acetaminophen-induced liver failure through mechanisms involving the regulation of neutrophil migration and NO production.
Sujet(s)
Lésions hépatiques dues aux substances , Maladies du foie , Souris , Animaux , Acétaminophène/toxicité , Leukocyte elastase/métabolisme , Souris de lignée BALB C , Transaminases , Lésions hépatiques dues aux substances/traitement médicamenteux , NécroseRÉSUMÉ
Estimating time of death is one of the most important problems in forensics. Here, we evaluated the applicability, limitations and reliability of the developed biological clock-based method. We analyzed the expression of the clock genes, BMAL1 and NR1D1, in 318 dead hearts with defined time of death by real-time RT-PCR. For estimating the time of death, we chose two parameters, the NR1D1/BMAL1 ratio and BMAL1/NR1D1 ratio for morning and evening deaths, respectively. The NR1D1/BMAL1 ratio was significantly higher in morning deaths and the BMAL1/NR1D1 ratio was significantly higher in evening deaths. Sex, age, postmortem interval, and most causes of death had no significant effect on the two parameters, except for infants and the elderly, and severe brain injury. Although our method may not work in all cases, our method is useful for forensic practice in that it complements classical methods that are strongly influenced by the environment in which the corpse is placed. However, this method should be applied with caution in infants, the elderly, and patients with severe brain injury.
Sujet(s)
Facteurs de transcription ARNTL , Lésions encéphaliques , Nourrisson , Humains , Sujet âgé , Facteurs de transcription ARNTL/génétique , Facteurs de transcription ARNTL/métabolisme , Reproductibilité des résultats , Horloges biologiques/génétique , Autopsie , Rythme circadien/génétiqueRÉSUMÉ
Aquaporins (AQPs) are a family of water channel proteins that primarily elicit the basic functions of water transport and osmotic homeostasis. To date, at least 17 mammalian AQPs have been identified, AQP-0 to -12 have been found in higher orders including human, and AQP-13 to -16 have been described in older lineages. Moreover, these proteins have recently been shown to regulate many biological processes through unique activities, such as cell proliferation, migration, apoptosis, and mitochondrial metabolism. Several studies have focused on the involvement of AQPs in cell biology aspect, showing that they are involved in a variety of physiological processes and pathophysiological conditions. Furthermore, in the field of forensic medicine, studies on whether AQPs can be a useful marker for diagnosing various causes of death have been conducted using autopsy samples and animal experiments, which have produced interesting results. Herein, we review certain observations regarding AQPs and discuss their potential to contribute to the future practice of forensic research.
Sujet(s)
Aquaporines , Animaux , Humains , Sujet âgé , Aquaporines/métabolisme , Transport biologique , Mammifères/métabolismeRÉSUMÉ
Estimating the age and vitality of human skin wounds is essential in forensic practice, and the use of immunohistochemical parameters in this regard remains a challenge. Heat shock proteins (HSPs) are evolutionarily conserved universal proteins that protect biological systems from various types of stress. However, its importance in forensic pathology for determining wound activation in neck compression skin remains unclear. The expression of HSP27 and HSP70 in neck skin samples was immunohistochemically examined to understand its forensic applicability in determining wound vitality. Skin samples were obtained from 45 cases of neck compression (hanging, 32 cases; strangulation, 10 cases; manual strangulation, 2 cases; other, 1 case) during forensic autopsies; intact skin from the same individual was used as a control. HSP27 expression was detected in 17.4% of keratinocytes in the intact skin samples. In the compressed region, the frequency of HSP27 expression in keratinocytes was 75.8%, which was significantly higher than that in intact skin. Similarly, HSP70 expression was 24.8% in intact skin samples and 81.9% in compressed skin samples, significantly higher in compressed skin than in intact skin samples. This increase in case compression cases may be due to the cell defence role of HSPs. From a forensic pathology perspective, the immunohistochemical examination of HSP27 and HSP70 expression in neck skin could be considered a valuable marker for diagnosing traces of antemortem compression.
Sujet(s)
Protéines du choc thermique HSP27 , Protéines du choc thermique , Humains , Protéines du choc thermique HSP27/métabolisme , Protéines du choc thermique/métabolisme , Protéines du choc thermique HSP70/métabolisme , Peau/métabolisme , Épiderme/métabolismeRÉSUMÉ
Neutralizing antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are being developed world over. We investigated the possibility of producing artificial antibodies from the formalin fixation and paraffin-embedding (FFPE) lung lobes of a patient who died by coronavirus disease 2019 (COVID-19). The B-cell receptors repertoire in the lung tissue where SARS-CoV-2 was detected were considered to have highly sensitive virus-neutralizing activity, and artificial antibodies were produced by combining the most frequently detected heavy and light chains. Some neutralizing effects against the SARS-CoV-2 were observed, and mixing two different artificial antibodies had a higher tendency to suppress the virus. The neutralizing effects were similar to the immunoglobulin G obtained from healthy donors who had received a COVID-19 mRNA vaccine. Therefore, the use of FFPE lung tissue, which preserves the condition of direct virus sensitization, to generate artificial antibodies may be useful against future unknown infectious diseases.
Sujet(s)
COVID-19 , Humains , SARS-CoV-2 , Vaccins contre la COVID-19 , Autopsie , Anticorps neutralisants , Formaldéhyde , Inclusion en paraffine , Récepteurs pour l'antigène des lymphocytes BRÉSUMÉ
Fibrosis and structural remodeling of the lung tissue can significantly impair lung function, often with fatal consequences. The etiology of pulmonary fibrosis (PF) is diverse and includes different triggers such as allergens, chemicals, radiation, and environmental particles. However, the cause of idiopathic PF (IPF), one of the most common forms of PF, remains unknown. Experimental models have been developed to study the mechanisms of PF, and the murine bleomycin (BLM) model has received the most attention. Epithelial injury, inflammation, epithelial-mesenchymal transition (EMT), myofibroblast activation, and repeated tissue injury are important initiators of fibrosis. In this review, we examined the common mechanisms of lung wound-healing responses after BLM-induced lung injury as well as the pathogenesis of the most common PF. A three-stage model of wound repair involving injury, inflammation, and repair is outlined. Dysregulation of one or more of these three phases has been reported in many cases of PF. We reviewed the literature investigating PF pathogenesis, and the role of cytokines, chemokines, growth factors, and matrix feeding in an animal model of BLM-induced PF.
Sujet(s)
Fibrose pulmonaire idiopathique , Lésion pulmonaire , Souris , Animaux , Bléomycine , Poumon/anatomopathologie , Fibrose , Inflammation/anatomopathologie , Fibrose pulmonaire idiopathique/anatomopathologie , Lésion pulmonaire/anatomopathologie , Transition épithélio-mésenchymateuse , Modèles animaux de maladie humaineRÉSUMÉ
In a previous work, authors have proposed a medico-legal definition of femicide as the murder due to the failure to recognize the right of self-determination of women. The aim of this paper was to apply the proposed definition to a cohort of cases to characterise femicides and female homicides and assess whether femicides can be considered a distinct entity or not. A comparison between female and male homicides was performed to assess common and distinctive features. Femicides were identified and compared to the cohort of non-femicide female murder. Results were compared to those reported in published forensic studies. Significant associations between female and male homicides were found for sex and partner/ex-partner offender, sex and indoor homicide and sex and asphyxia as dynamic of death emerged. A higher prevalence of indoor homicides and asphyxiation and of partner relationships were documented in female homicides. Gunshot, blunt injuries and cut wounds are well represented in both types of homicides. Most affected sites are back and chest in male homicides, and head, breasts, pubis, and limbs in female homicides. When comparing femicides and female homicides, a positive association between strangulation as harmful mean and a negative one between femicides and indoor homicides were found. Male and female homicides can be considered as two distinct victimological phenomena. Focusing on femicide allows to establish injuries and circumstantial patterns, that could represent evidence of a specific murder. More studies with a standardized data collection are needed to corroborate the theory of this paper.
Sujet(s)
Victimes de crimes , Humains , Mâle , Femelle , Études rétrospectives , Médecine légale , Homicide , AsphyxieRÉSUMÉ
We investigated the dynamics of the gene expression of M1 and M2 macrophage markers during skin wound healing in mice. Expression of M1-macrophage markers, such as Il12a, Tnf, Il6, Il1b, and Nos2 was upregulated after wounding and peaked at 1 or 3 days after injury, and that of M2-macrophage markers such as Mrc1, Cd163, Ccl17, Arg, and Tgfb1, peaked at 6 days after injury. Consistent with these findings, using triple-color immunofluorescence analysis revealed that F4/80+CD80+ M1 macrophages were more abundant than F4/80+CD206+ M2 macrophages on day 3 in mouse wound specimens, and that M2 macrophages were prominently detected in day 6 wounds. For application in forensic practice, we examined macrophage polarization using human wound specimens. The average ratios of CD68+iNOS+ M1 macrophages to CD68+CD163+ M2 macrophages (M1/M2 ratios) were greater than 2.5 for the wounds aged 2-5 days. Out of 11 wounds aged 1-5 days, five samples had the M1/M2 ratios of > 3.0. These observations propose that the M1/M2 ratios of 3.0 would indicate a wound age of 1-5 days as the forensic opinion. This study showed that M1 and M2 macrophages in human skin wound might be a promising marker for wound age determination.
Sujet(s)
Macrophages , Souris , Humains , Animaux , Macrophages/métabolisme , Marqueurs biologiques/métabolismeRÉSUMÉ
Ubiquitin is a member of the heat shock protein family and is rapidly induced by various types of stimuli, including ischemic and mechanical stress. However, its significance in determining wound vitality of neck compression skin in forensic pathology remains unclear. We immunohistochemically examined the expression of ubiquitin in the neck skin samples to understand its forensic applicability in determining wound vitality. Skin samples were obtained from 53 cases of neck compression (hanging, 42 cases; strangulation, 11 cases) during forensic autopsies. Intact skin from the same individual was used as the control. Ubiquitin expression was detected in 73.9% of keratinocytes in intact skin samples, but only in 21.2% of keratinocytes in the compression regions, with statistical differences between the control and compression groups. This depletion in the case of neck compression may be caused by the impaired conversion of conjugated to free ubiquitin and failure of de novo ubiquitin synthesis. From a forensic pathological perspective, immunohistochemical examination of ubiquitin expression in the skin of the neck can be regarded as a valuable marker for diagnosing traces of antemortem compression.
RÉSUMÉ
Whereas the COVID-19 disease pathophysiology is under investigation, it is important to identify the pathways of viral transmission and inflammation from the pre-illness to the disease-onset stages. We analyzed five lung lobes from a patient with COVID-19 who finally died after prolonged lung protective ventilation. Pathological examination revealed moderate inflammation in upper lung lobes and uneven yet severe inflammation and diffuse alveolar damage in lower lung lobes. SARS-CoV-2 was detected at higher levels not in severely, but rather moderately inflamed middle lung lobes, and immunohistochemistry and bulk RNA-sequencing results showed that immune cells were detected at higher levels in lower lung lobes. The mRNA expression of cytokine families varied. We found an increase in keratin 5- or aquaporin 3-expressing basal cells in the severely inflamed lower lung lobes, and the alveolar stromal tissues were filled with them. Thus, this analysis of lung samples from a patient helps to determine the COVID-19 pathophysiology at a specific time point, and the virus localization and inflammatory responses at each site of the lungs provide various important indications.