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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.
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Inmunohistoquímica , Metaloproteinasa 9 de la Matriz , Cicatrización de Heridas , Humanos , Metaloproteinasa 9 de la Matriz/metabolismo , Proyectos Piloto , Masculino , Piel/lesiones , Piel/patología , Piel/metabolismo , Factores de Tiempo , Persona de Mediana Edad , Patologia Forense , Adulto , Femenino , Biomarcadores/metabolismo , Biomarcadores/análisis , AncianoRESUMEN
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.
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Inmunohistoquímica , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas , Piel , Humanos , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/metabolismo , Piel/lesiones , Piel/patología , Piel/metabolismo , Piel/química , Masculino , Femenino , Persona de Mediana Edad , Adulto , Patologia Forense , Factores de Tiempo , Anciano , Anciano de 80 o más AñosRESUMEN
PURPOSE: The transmembrane serine protease 4 (TMPRSS4) gene is upregulated in various human cancers. However, its biological functions in pancreatic ductal adenocarcinoma remain unclear. We examined the expression of TMPRSS4 in pancreatic ductal adenocarcinoma tissues and its correlation with clinicopathological parameters in patients with pancreatic ductal adenocarcinoma who underwent surgery. METHODS: The TMPRSS4 expression was immunohistochemically examined in 81 PDAC patients with pancreatic ductal adenocarcinoma. We analyzed the association between the TMPRSS4 expression and clinicopathological factors, the recurrence-free survival (RFS), and the overall survival (OS) and examined the effect of TMPRSS4 expression on cell migration and sensitivity to 5-fluorouracil. RESULTS: The expression rate of TMPRSS4 in the samples was 62.9% (51/81). The TMPRSS4 expression was not correlated with any clinicopathological feature. The five-year overall and recurrence-free survival rates were significantly lower in the TMPRSS4-positive group than in the TMPRSS4-negative group. On a multivariate analysis, TMPRSS4 positivity, poorly differentiated histology, and non-adjuvant chemotherapy predicted a poor OS, while TMPRSS4 positivity and poorly differentiated histology predicted a poor RFS. TMPRSS4-silenced pancreatic ductal adenocarcinoma cells showed higher sensitivity to 5- fluorouracil than did the control siRNA-transfected cells. CONCLUSIONS: TMPRSS4 can be considered a prognostic factor and therapeutic target for pancreatic ductal adenocarcinoma.
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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.
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Carcinoma Hepatocelular , Ablación por Catéter , Neoplasias Hepáticas , Ablación por Radiofrecuencia , Femenino , Humanos , Persona de Mediana Edad , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/patología , Hemoperitoneo/etiología , Ablación por Catéter/efectos adversos , Ablación por Catéter/métodos , Ablación por Radiofrecuencia/efectos adversosRESUMEN
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.
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Fibrosis Pulmonar Idiopática , Lesión Pulmonar , Ratones , Animales , Bleomicina , Pulmón/patología , Fibrosis , Inflamación/patología , Fibrosis Pulmonar Idiopática/patología , Lesión Pulmonar/patología , Transición Epitelial-Mesenquimal , Modelos Animales de EnfermedadRESUMEN
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.
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Enfermedad Hepática Inducida por Sustancias y Drogas , Hepatopatías , Ratones , Animales , Acetaminofén/toxicidad , Elastasa de Leucocito/metabolismo , Ratones Endogámicos BALB C , Transaminasas , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , NecrosisRESUMEN
OBJECTIVES: LN comprises various glomerular lesions, including endocapillary hypercellularity with macrophage infiltration. In this study, we aimed to clarify the involvement of macrophage-tropic chemokine receptors in the pathogenesis of these glomerular lesions. METHODS: MRL/lpr mouse-derived monoclonal IgG3 antibody-producing hybridomas, 2B11.3 and B1, were injected intraperitoneally into BALB/c mice [wild type (WT)] to induce endocapillary hypercellularity and wire-loop lesions, respectively. The expression of chemokine and chemokine receptors was analysed by quantitative real-time PCR and IF. The roles of chemokine receptors in these lesions were evaluated using chemokine receptor-deficient mice or a selective CCR5 antagonist, maraviroc. RESULTS: 2B11.3 caused glomerular endocapillary hypercellularity with a significant number of glomerular CD68-positive macrophages. Further, enhanced expression of CCL2, CCL3, CCR2, CCR5 and CX3CR1 was observed in the renal cortex, compared with B1 injection, which induced wire-loop lesions. In 2B11.3-induced glomerular lesions, CD68 -positive glomerular macrophages expressed CCL2, CCL3, CCR2, CCR5 and CX3CR1, while glomerular endothelial cells expressed CCL2, CCL3, CX3CL1 and CCR2. When 2B11.3 was injected, CCR2-/- and CCR5-/-, but not CX3CR1-/-, mice exhibited reduced endocapillary hypercellularity, attenuated glomerular macrophage infiltration and improved serum blood urea nitrogen levels. Only CCR2-/- mice developed wire-loop lesions. B1 injection caused wire-loop lesions in these chemokine receptor-deficient mice to a similar extent as WT. Maraviroc treatment reduced 2B11.3-induced endocapillary hypercellularity and improved serum blood urea nitrogen levels. CONCLUSION: CCR2 and CCR5 regulate glomerular macrophage infiltration and contribute to the development of glomerular endocapillary hypercellularity in LN. CCR5 inhibition can be a specific therapy for endocapillary hypercellularity without inducing wire-loop lesions.
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Enfermedades Renales , Nefritis Lúpica , Receptores CCR2 , Receptores CCR5 , Animales , Anticuerpos Monoclonales , Células Endoteliales/metabolismo , Inmunoglobulina G/metabolismo , Enfermedades Renales/metabolismo , Nefritis Lúpica/patología , Macrófagos/metabolismo , Maraviroc/metabolismo , Ratones , Ratones Endogámicos MRL lpr , Receptores CCR2/genética , Receptores CCR2/metabolismo , Receptores CCR5/genética , Receptores CCR5/metabolismoRESUMEN
Aquaporins (AQPs) are membrane-bound proteins for water transportation and are useful for diagnosing drowning and wound vitality in forensic pathology. Here, we examined intrathrombotic expression of AQP-1 and AQP-3 using deep vein thrombosis models in mice. To perform immunohistochemical analyses, we used anti-AQP-1 and anti-AQP-3 antibodies. In thrombus samples with the post-ligation intervals of 1 to 5 days, AQP-1+ areas were over 70%. At 7 days after the IVC ligation, AQP-1+ areas became less than 50%, eventually decreasing to 11% at 21 days. At 3 days after the IVC ligation, AQP-3+ cells started to appear from the peripheral area. Thereafter, the positive cell number progressively increased and reached to a peak at 10 days after the IVC ligation. When the intrathrombotic AQP-1+ area was as large as the intrathrombotic collagen area or smaller, it would indicate a thrombus age of ≥ 10 days. AQP-3+ cell number of > 30 would indicate a thrombus age of 10-14 days. Collectively, our study implied that the detection of AQP-1 and AQP-3 would be useful for the determination of thrombus age.
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Acuaporina 1/sangre , Acuaporina 3/sangre , Vena Cava Inferior/patología , Trombosis de la Vena/patología , Animales , Modelos Animales de Enfermedad , Patologia Forense , Inmunohistoquímica , Ratones , Ratones Endogámicos BALB CRESUMEN
We report a suicide case of complete decapitation using a self-constructed guillotine. A 45-year-old man, whose body was severely burned, was found dead. The head was completely separated from the middle level of the neck, and a sharp blade with a steel frame was placed between the head and neck. The severance plane passed between the C4 and C5 vertebrae. Vital reactions such as hemorrhage could not be confirmed at the decapitated skin edge because the body was severely burned. Both common carotid arteries were sharply transected. Subendocardial hemorrhage was detected in the left ventricle. Only a little blood, but no soot, was detected in the respiratory tract, including the trachea and bilateral bronchi. Subarachnoid hemorrhage was noted at the edge of the cervical spinal cord. The saturation level of CO-Hb was 5.7% in the left cardiac blood, 5.9% in the right cardiac blood, and 5.8% in the peripheral blood from the femoral vein. Cervical transection was diagnosed as the cause of death. We believe that he was unintentionally burned by spread fire from an automobile after decapitation by a self-constructed guillotine.
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Quemaduras/patología , Decapitación , Suicidio Completo , Carboxihemoglobina/análisis , Traumatismos de las Arterias Carótidas/patología , Incendios , Ventrículos Cardíacos/patología , Hemorragia/patología , Humanos , Masculino , Persona de Mediana Edad , Sistema Respiratorio/patología , Hemorragia Subaracnoidea/patologíaRESUMEN
ABSTRACT: Oba, K, Samukawa, M, Nakamura, K, Mikami, K, Suzumori, Y, Ishida, Y, Keeler, N, Saitoh, H, Yamanaka, M, and Tohyama, H. Influence of constant torque stretching at different stretching intensities on flexibility and mechanical properties of plantar flexors. J Strength Cond Res 35(3): 709-714, 2021-The purpose of this study was to examine the effects of constant torque stretching (CTS) at different stretching intensities on the maximal range of motion (ROM) and muscle-tendon unit (MTU) stiffness of plantar flexors. Fourteen healthy men performed 4 trials of differing stretch intensities: no stretching (control), 50, 75, and 100%. Stretch intensity was defined as maximum passive resistive torque predetermined at a familiarization trial. Each stretch trial consisted of 5 sets of 60-second CTS at the designated stretch intensity. Both maximal ROM and passive resistive torque were assessed during passive dorsiflexion, and MTU stiffness was calculated using the torque-angle curves measured before and after CTS. There were no significant differences in maximal ROM or MTU stiffness at the baseline condition. After the intervention, significantly greater maximal ROM and significantly lower MTU stiffness were observed in the 100% CTS condition than the control condition, whereas there were no significant differences between the submaximal intensity condition (i.e., 50 or 75% intensity) and the control condition. Therefore, our findings suggest that maximal intensity stretching is the most effective approach for improving both flexibility and MTU stiffness with CTS.
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Ejercicios de Estiramiento Muscular , Humanos , Masculino , Músculo Esquelético , Rango del Movimiento Articular , Tendones , TorqueRESUMEN
The twist-bend nematic (NTB ) phase with a heliconical nanostructure of the local director generating symmetry breaking by achiral bent-shaped molecules is a hot topic of current liquid-crystal science. As opposed to the most common methylene-linked dimers, this study demonstrates chalcogen ether- and/or thioether-linked 6-(4-cyanophenyl)-2-naphthyl-based liquid-crystal dimers with symmetric and asymmetric π-conjugated mesogenic-arm structures that exhibit the NTB phase. Although the symmetric bis(ether)-linked dimer exhibits only the conventional nematic (N) phase, the asymmetric bis(ether)-linked dimer can form the NTB phase. All thioether-linked dimers form the NTB phase, wherein the dimers with asymmetric arms vitrify in the NTB phase on cooling to room temperature. The phase transitions are discussed in terms of the chalcogen linkage combination, mesogenic-arm symmetry, and spacer length. It is revealed that thioether-linked dimers based on asymmetric π-conjugated mesogenic arms with terminal cyano groups are highly beneficial for the realization of materials that form a wide range of NTB phases and glassy NTB states at room temperature.
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We immunohistochemically examined the intrathrombotic dynamics of autophagy during thrombogenesis using murine deep vein thrombosis (DVT) models. To perform the immunohistochemical analyses, we used anti-LC3 antibody and anti-p62 antibody for detecting the intrathrombotic autophagic functions. We estimated dynamics of the intrathrombotic autophagy as LC3+ cell number (×1000, five fields) with the thrombus ages (each group n = 5). The number of LC3+ cells was once decreased at 3 days, and then increased until 10 days. On the contrary, the number of p62+ cells progressively increased until 10 days after the inferior vena cava (IVC) ligation, and then gradually decreased. Especially, in all of thrombus samples with the postligation intervals of 5-10 days, both numbers were larger than 10. Subsequently, we compared the number of LC3+ cells to that of p62+ cells. Although, at 1 day after the IVC ligation, LC3+ cell number significantly exceeded p62+ cell number, the former was significantly or relatively less than the latter at 3 days or more after the IVC ligation. Thus, positive cells of > 10 in both LC3 and p62 indicated the thrombus age of 5-10 days. Upon comparison of immunopositive cells in LC3 and p62, the p62/LC3 ratio was > 1.0 in 29 out of 30 thrombus samples aged 3-21 days, and all of 1-day-old thrombus had the p62/LC3 ratio of < 0.5. Thus, the ratio of > 1.0 and that of < 0.5 could indicate thrombus age of 3 days or more and that of 1 day, respectively. Collectively, our study implied that the detection of autophagy-related molecules such as LC3 and p62 would be useful for the determination of thrombus age.
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Autofagia , Proteínas Asociadas a Microtúbulos/metabolismo , Proteína Sequestosoma-1/metabolismo , Trombosis/patología , Vena Cava Inferior , Trombosis de la Vena/patología , Animales , Modelos Animales de Enfermedad , Patologia Forense , Inmunohistoquímica , Ligadura , Masculino , Ratones , Ratones Endogámicos BALB C , Trombosis/diagnóstico , Factores de Tiempo , Trombosis de la Vena/diagnósticoRESUMEN
Dendritic cells (DCs) can essentially contribute to innate and adaptive immune system in various organs. A double-color immunofluorescence analysis was carried out with anti-CD11c and -HLA-DRα antibodies to detect DCs in 53 skin wounds (their postinfliction intervals: group I, 0-3 days; group II, 4-7 days; group III, 9-14 days; and group IV, 17-21 days). CD11c+HLA-DRα+ DCs were first observed in skin wounds with postinfliction intervals of 3 days, and the DC numbers were found to be elevated in skin wounds with the subsequent increase in postinfliction intervals. Semi-quantitative morphometric analyses showed that the DC number was the highest in the 12-day-old wound. More than 50 DCs were present in 8 of 10 samples (80%) in group II and 14 of 16 samples (87.5%) in group III, and there was no difference between the two groups. Thus, the presence of DCs in a skin wound was possibly estimated as postinfliction intervals of at least 3 days. Furthermore, when a skin wound contained > 50 DCs, its age would be judged as 4-14 days. Collectively, the appearance of DCs in human skin wounds may provide useful information in determining the age of a wound.
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Células Dendríticas , Patologia Forense , Piel/lesiones , Cicatrización de Heridas/inmunología , Adolescente , Adulto , Anciano , Antígeno CD11c , Niño , Técnica del Anticuerpo Fluorescente , Antígenos HLA-DR , Humanos , Persona de Mediana Edad , Traumatismos de los Tejidos Blandos/inmunología , Factores de Tiempo , Heridas Penetrantes/inmunología , Adulto JovenRESUMEN
This paper presents an unusual complex suicide case that died of nicotine addiction. The deceased was a 40-year-old male who was found lying dead on the floor in his room. In external findings, many incision wounds on his forearms and skin discoloration with epidermolysis on his cervical region could be seen. In the room, a blood-stained scissors and electric cord hanged on the exercise bike were found. Moreover, nine cigarette residues which were only the filter part and empty bottle of coffee were found on his side. At autopsy, we found that those injuries were not serious enough to lead him to the death. Toxicologically, caffeine, nicotine, cotinine, mirtazapine, and olanzapine could be detected, and the concentrations of nicotine were 3.740, 2.140, 3.100, and 451.100 µg/ml in cardiac blood, peripheral blood, urine, and stomach contents, respectively. These concentrations were evaluated as the fatal levels, and the cause of his death was diagnosed as acute nicotine intoxication.
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Análisis Químico de la Sangre , Toxicología Forense , Contenido Digestivo/química , Nicotina/envenenamiento , Suicidio Completo , Adulto , Autopsia , Cafeína/análisis , Cotinina/análisis , Humanos , Masculino , Mirtazapina/análisis , Olanzapina/análisisRESUMEN
Programmed cell death ligand 1 (PD-L1) on tumor cells suppresses anti-tumor immunity and has an unfavorable prognostic impact in ovarian cancer patients. We herein report the pathophysiological and therapeutic impacts of PD-L1 disruption in ovarian cancer. PD-L1 was genetically disrupted in the murine ovarian cancer cell line ID8 using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-mediated genome editing. PD-L1 knockout (KO) and control ovarian cancer cells were intraperitoneally inoculated into syngeneic mice, and survival and tumor dissemination were evaluated. Survival times were significantly longer in the PD-L1-KO ID8-inoculated groups than in their control groups, and its therapeutic benefit was enhanced in combination with the cisplatin treatment. Tumor weights and ascites volumes were significantly lower in the PD-L1-KO ID8 groups than in their control groups. Immunohistochemical and immunofluorescence analyses showed that intratumoral CD4+ T cells, CD8+ T cells, NK cells and CD11c+ M1 macrophages were significantly increased, whereas regulatory T cells were significantly decreased in the PD-L1-KO ID8 groups compared with those in their control groups. The intratumoral mRNA expression of interferon-γ, tumor-necrosis factor-α, interleukin (IL)-2, IL-12a, CXCL9 and CXCL10 was significantly stronger, while that of IL-10, vascular endothelial growth factor, CXCL1 and CXCL2 was significantly weaker in the PD-L1-KO ID8 groups. These results indicate that CRISPR/Cas9-mediated PD-L1 disruption on tumor cells promotes anti-tumor immunity by increasing tumor-infiltrating lymphocytes and modulating cytokine/chemokine profiles within the tumor microenvironment, thereby suppressing ovarian cancer progression. These results suggest that PD-L1-targeted therapy by genome editing may be a novel therapeutic strategy for ovarian cancer.
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Antígeno B7-H1/metabolismo , Sistemas CRISPR-Cas , Edición Génica , Inmunidad , Neoplasias Ováricas/genética , Neoplasias Ováricas/metabolismo , Animales , Antígeno B7-H1/genética , Línea Celular Tumoral , Supervivencia Celular/genética , Citocinas/metabolismo , Progresión de la Enfermedad , Ensayo de Inmunoadsorción Enzimática , Femenino , Eliminación de Gen , Sitios Genéticos , Humanos , Inmunomodulación , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismo , Linfocitos Infiltrantes de Tumor/patología , Macrófagos/inmunología , Macrófagos/metabolismo , Ratones , Metástasis de la Neoplasia , Neoplasias Ováricas/inmunología , Neoplasias Ováricas/patologíaRESUMEN
Objective- Deep vein thrombosis results from a combination of risk factors including genetic conditions, obesity, drugs, pregnancy, aging, and malignancy. We examined pathophysiological roles of the TNF-α (tumor necrosis factor-α)-TNF-Rp55 (tumor necrosis factor receptor p55) axis in thrombus resolution using Tnfrp55-/- (TNF-Rp55-deficient) mice. Approach and Results- On ligating the inferior vena cava of wild-type (WT) mice, venous thrombi formed and grew progressively until 5 days but shrunk to <50% of the thrombus weight at day 14. Concomitantly, inferior vena cava ligation enhanced intrathrombotic gene expression of Tnfa and Tnfrp55, and intrathrombotic macrophages expressed both TNF-α and TNF-Rp55 proteins. In Tnfrp55-/- mice treated with the same manner, thrombus formed at a similar rate for 5 days, but shrinking was delayed compared with WT mice. Moreover, the blood flow recovery in thrombosed inferior vena cava was suspended in Tnfrp55-/- mice compared with WT mice. Intrathrombotic Plau (urokinase-type plasminogen activator), Mmp2 (matrix metalloproteinase 2), and Mmp9 (matrix metalloproteinase 9) mRNA expression was significantly reduced in Tnfrp55-/- mice, compared with WT ones. Supportingly, the administration of anti-TNF-α antibody or TNF-α inhibitor (etanercept) delayed the thrombus resolution in WT mice. Furthermore, TNF-α treatment enhanced gene expression of Plau, Mmp2, and Mmp9 in WT macrophages but not Tnfrp55-/- macrophages. These effects were significantly suppressed by ERK (extracellular signal regulated kinase) and NF-κB (nuclear factor-kappa B) inhibitors. Therefore, the lack of TNF-Rp55 has detrimental roles in the thrombus resolution by suppressing PLAU, MMP-2, and MMP-9 expression. In contrast, TNF-α administration accelerated thrombus resolution in WT but not Tnfrp55-/- mice. Conclusions- The TNF-α-TNF-Rp55 axis may have essential roles in the resolution of venous thrombus in mice.
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Receptores Tipo I de Factores de Necrosis Tumoral/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Vena Cava Inferior/metabolismo , Trombosis de la Vena/metabolismo , Animales , Células Cultivadas , Modelos Animales de Enfermedad , Macrófagos Peritoneales/metabolismo , Masculino , Metaloproteinasa 2 de la Matriz/genética , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/metabolismo , Ratones Endogámicos BALB C , Ratones Noqueados , Receptores Tipo I de Factores de Necrosis Tumoral/deficiencia , Receptores Tipo I de Factores de Necrosis Tumoral/genética , Transducción de Señal , Factores de Tiempo , Activador de Plasminógeno de Tipo Uroquinasa/genética , Activador de Plasminógeno de Tipo Uroquinasa/metabolismo , Vena Cava Inferior/patología , Trombosis de la Vena/sangre , Trombosis de la Vena/patologíaRESUMEN
We describe a case of suicidal asphyxiation using a plastic bag combined with carbon dioxide (CO2) gas. A 20-year-old male, whose head was covered with a plastic bag, was found dead in his room. In the plastic bag, there were two glass-made cups containing liquid-like substance. Through crime scene investigation by police staffs, a bottle of citric acid and a box of baking soda were also discovered in his room. The forensic autopsy revealed that there were neither lesions nor injuries in all of the organs. Moreover, any drugs and poisons could not be detected in blood samples. Based on autopsy findings and crime scene investigation, the cause of death was diagnosed as acute asphyxia due to CO2 intoxication by the mixture of citric acid with baking soda in the plastic bag. To the best of our knowledge, there are no medical literatures describing plastic bag suffocation combined with CO2 gas generated from citric acid and baking soda, which has been widely distributed as suicidal means through websites. This case report promotes forensic pathologists and medical coroners to emphasize that the Internet has a crucial role on a source of suicidal information or a promoter of suicide all over the world.
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Asfixia/etiología , Ácido Cítrico/química , Bicarbonato de Sodio/química , Suicidio , Dióxido de Carbono , Humanos , Masculino , Adulto JovenRESUMEN
It has been reported that the intake of milk basic protein (MBP) increases bone density by promoting bone formation and suppressing bone resorption. However, few studies have been done on MBP in cartilage, the tissue adjacent to bone. We therefore investigated the effect of MBP on a chondrocyte cell line, ATDC5. In a proliferative assay using the WST-1 method, the addition of 10, 100, and 1,000 µg/mL of MBP to ATDC5 cells significantly increased the cell number by about 1.2-, 1.5-, and 1.7-fold, respectively, compared with the control cells. The cell cycle analysis using flow-cytometry revealed that the proportion of S- and G2/M-phase cells was increased but that of G0/G1 phase was decreased in a dose-dependent manner with MBP addition. We measured the alkaline phosphatase activity of MBP-treated ATDC5 cells to examine the differentiation stage of the cells. Alkaline phosphatase activity was suppressed in a dose-dependent manner with MBP addition and was especially drastic at higher doses of MBP (100 and 1,000 µg/mL). The Alizarin Red S staining intensity, the indicator for calcification of cells, was lower in the MBP-treated (100 µg/mL) cells than in nontreated control cells. In the reverse-transcription PCR experiment, the mRNA level of SRY-box containing gene 9 (Sox9) and type II collagen (Col2) was significantly increased in the MBP-treated cells compared with the control cells. A significant decrease of the mRNA level of runt-related transcription factor 2 (Runx2) and type X collagen (Col10) was also observed in the MBP-treated cells. These results suggested that MBP promoted the proliferation of chondrocytes by suppressing their differentiation toward calcification.
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Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Condrocitos/efectos de los fármacos , Condrogénesis/efectos de los fármacos , Proteínas de la Leche/farmacología , Animales , Cartílago , Línea Celular , Colágeno Tipo II , Ratones , Leche/química , Osteogénesis , ARN MensajeroRESUMEN
In forensic practices, it is often difficult to determine wound vitality in compression marks of the neck with naked eyes. AQP1 and AQP3 are the major water channels associated with skin. Thus, we immunohistochemically examined the expression of AQP1 and AQP3 in neck skin samples to discuss their forensic applicability to determination of the wound vitality. Skin samples were obtained from 56 neck compression cases (hanging, 35 cases; strangulation, 21 cases). The intact skin from the same individual was taken as a control. Although AQP1 was immnunostained in dermal capillaries in both the neck compression marks and intact skin samples, there was no significant difference in the magnitude of AQP1 expression between both groups. On the contrary, AQP3-positive signals could be faintly detected in uninjured skin samples, and the positive signals seemed more intense in the keratinocytes in compression regions. Morphometrical analyses revealed that the ratio of AQP3-expressed keratinocytes was significantly enhanced in neck compression regions, compared with control groups. From the viewpoints of forensic pathology, immunohistochemical detection of AQP3 in the neck skin can be considered a valuable marker to diagnose the trace of antemortem compression.