RESUMO
The time since deposition (TSD) of a bloodstain, i.e., the time of a bloodstain formation is an essential piece of biological evidence in crime scene investigation. The practical usage of some existing microscopic methods (e.g., spectroscopy or RNA analysis technology) is limited, as their performance strongly relies on high-end instrumentation and/or rigorous laboratory conditions. This paper presents a practically applicable deep learning-based method (i.e., BloodNet) for efficient, accurate, and costless TSD inference from a macroscopic view, i.e., by using easily accessible bloodstain photos. To this end, we established a benchmark database containing around 50,000 photos of bloodstains with varying TSDs. Capitalizing on such a large-scale database, BloodNet adopted attention mechanisms to learn from relatively high-resolution input images the localized fine-grained feature representations that were highly discriminative between different TSD periods. Also, the visual analysis of the learned deep networks based on the Smooth Grad-CAM tool demonstrated that our BloodNet can stably capture the unique local patterns of bloodstains with specific TSDs, suggesting the efficacy of the utilized attention mechanism in learning fine-grained representations for TSD inference. As a paired study for BloodNet, we further conducted a microscopic analysis using Raman spectroscopic data and a machine learning method based on Bayesian optimization. Although the experimental results show that such a new microscopic-level approach outperformed the state-of-the-art by a large margin, its inference accuracy is significantly lower than BloodNet, which further justifies the efficacy of deep learning techniques in the challenging task of bloodstain TSD inference. Our code is publically accessible via https://github.com/shenxiaochenn/BloodNet. Our datasets and pre-trained models can be freely accessed via https://figshare.com/articles/dataset/21291825.
Assuntos
Manchas de Sangue , Teorema de Bayes , Aprendizado de MáquinaRESUMO
BACKGROUND: Microorganisms distribute and proliferate both inside and outside the body, which are the main mediators of decomposition after death. However, limited information is available on the postmortem microbiota changes of extraintestinal body sites in the early decomposition stage of mammalian corpses. RESULTS: This study investigated microbial composition variations among different organs and the relationship between microbial communities and time since death over 1 day of decomposition in male C57BL/6 J mice by 16S rRNA sequencing. During 1 day of decomposition, Agrobacterium, Prevotella, Bacillus, and Turicibacter were regarded as time-relevant genera in internal organs at different timepoints. Pathways associated with lipid, amino acid, carbohydrate and terpenoid and polyketide metabolism were significantly enriched at 8 h than that at 0.5 or 4 h. The microbiome compositions and postmortem metabolic pathways differed by time since death, and more importantly, these alterations were organ specific. CONCLUSION: The dominant microbes differed by organ, while they tended toward similarity as decomposition progressed. The observed thanatomicrobiome variation by body site provides new knowledge into decomposition ecology and forensic microbiology. Additionally, the microbes detected at 0.5 h in internal organs may inform a new direction for organ transplantation.
Assuntos
Microbiota , Mudanças Depois da Morte , Masculino , Animais , Camundongos , RNA Ribossômico 16S/genética , Camundongos Endogâmicos C57BL , Cadáver , Microbiota/genética , Mamíferos/genéticaRESUMO
Microorganisms play a vital role in the decomposition of vertebrate remains in natural nutrient cycling, and the postmortem microbial succession patterns during decomposition remain unclear. The present study used hierarchical clustering based on Manhattan distances to analyze the similarities and differences among postmortem intestinal microbial succession patterns based on microbial 16S rDNA sequences in a mouse decomposition model. Based on the similarity, seven different classes of succession patterns were obtained. Generally, the normal intestinal flora in the cecum was gradually decreased with changes in the living conditions after death, while some facultative anaerobes and obligate anaerobes grew and multiplied upon oxygen consumption. Furthermore, a random forest regression model was developed to predict the postmortem interval based on the microbial succession trend dataset. The model demonstrated a mean absolute error of 20.01 h and a squared correlation coefficient of 0.95 during 15-day decomposition. Lactobacillus, Dubosiella, Enterococcus, and the Lachnospiraceae NK4A136 group were considered significant biomarkers for this model according to the ranked list. The present study explored microbial succession patterns in terms of relative abundances and variety, aiding in the prediction of postmortem intervals and offering some information on microbial behaviors in decomposition ecology.
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Microbioma Gastrointestinal , Camundongos , Animais , Mudanças Depois da Morte , Bactérias/genética , Intestinos , LactobacillusRESUMO
OBJECTIVE: To investigate the effects of vasoactive intestinal peptide on the blood brain barrier function after focal cerebral ischemia in rats. MATERIALS AND METHODS: Rats were intracerebroventricular injected with vasoactive intestinal peptide after a two hours middle cerebral artery occlusion. Functional outcome was studied with the neurological severity score. The brain edema and the infarction were evaluated via histology. The blood brain barrier permeability was assessed using Evans Blue dye injection method. We also measure the apoptosis of brain microvascular endothelial cells and brain levels of B-cell leukemia-2 protein by immunohistochemical analysis and western blotting, respectively. RESULTS: In contrast to the cases treated with vehicle at 72 h after middle cerebral artery occlusion, the treatment with vasoactive intestinal peptide significantly (P < 0.05) reduced the neurological severity score, the brain edema and infarct volume. The Evans Blue leakage and brain water content were obviously reduced (P < 0.05) in vasoactive intestinal peptide-treated rats compared with those of control rats at 72 and 96 h after stroke. In addition, vasoactive intestinal peptide decreased the numbers of terminal deoxynucleotidyl transferase-mediated dUTP-nick end labeling positive endothelial cells and increased the protein levels of B-cell leukemia-2 in the ischemic hemisphere at 72 h after ischemia. CONCLUSIONS: Our data suggest that treatment with vasoactive intestinal peptide ameliorates the blood brain barrier function, contributing to reduce in brain damage both morphologically and functionally in the ischemic rat. This amelioration may be associated with attenuation in apoptosis of brain microvascular endothelial cells by increased B-cell leukemia-2 expression.
Assuntos
Edema Encefálico , Isquemia Encefálica , Animais , Barreira Hematoencefálica/metabolismo , Edema Encefálico/tratamento farmacológico , Edema Encefálico/etiologia , Edema Encefálico/prevenção & controle , Células Endoteliais/metabolismo , Humanos , Infarto da Artéria Cerebral Média/metabolismo , Ratos , Ratos Sprague-Dawley , Peptídeo Intestinal Vasoativo/metabolismo , Peptídeo Intestinal Vasoativo/farmacologiaRESUMO
Trauma is one of the most common conditions in the biomedical field. It is important to identify it quickly and accurately. However, when evanescent trauma occurs, it presents a great challenge to professionals. There are few reports on the establishment of a rapid and accurate trauma identification and prediction model. In this study, Fourier transform infrared spectroscopy (FTIR) and microscopic spectroscopy (micro-IR) combined with chemometrics were used to establish prediction models for the rapid identification of muscle trauma in humans and rats. The results of the average spectrum, principal component analysis (PCA) and loading maps showed that the differences between the rat muscle trauma group and the rat control group were mainly related to biological macromolecules, such as proteins, nucleic acids and carbohydrates. The differences between the human muscle trauma group and the human control group were mainly related to proteins, polysaccharides, phospholipids and phosphates. Then, a partial least squares discriminant analysis (PLS-DA) was used to evaluate the classification ability of the training and test datasets. The classification accuracies were 99.10% and 93.69%, respectively. Moreover, a trauma classification and recognition model of human muscle tissue was constructed, and a good classification effect was obtained. The classification accuracies were 99.52% and 91.95%. In conclusion, spectroscopy and stoichiometry have the advantages of being rapid, accurate and objective and of having high resolution and a strong recognition ability, and they are emerging strategies for the identification of evanescent trauma. In addition, the combination of spectroscopy and stoichiometry has great potential in the application of medicine and criminal law under practical conditions.
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Quimiometria , Doenças Musculares , Humanos , Ratos , Animais , Análise Discriminante , Análise dos Mínimos Quadrados , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Análise de Componente Principal , MúsculosRESUMO
Many recent studies investigate the economic effect of the COVID-19 pandemic in multiple aspects, while whether and how the sovereign credit risk reacts to the shock is still underexplored. Using a sample of forty developed and developing countries and employing staggered difference-in-differences models, we find that the sovereign credit risk measured by sovereign credit default swap spreads significantly increases after the COVID-19 pandemic outbreak, and the adverse effect is more pronounced for short-term credit risk. The reason is that the pandemic causes severe concerns about aggregate consumption contraction in addition to the fiscal capacity and the volatility of exports. We also find that fiscal stimuli stabilizing consumer spending alleviate the adverse effect of the COVID-19 pandemic, while debt relief does not matter. Overall, practitioners and policy makers should attach more importance to consumption and its recovery during the pandemic when making decisions.
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Monoubiquitination of histone H2B on lysine 120 (H2Bub1) is an epigenetic mark generally associated with transcriptional activation, yet the global functions of H2Bub1 remain poorly understood. Ferroptosis is a form of non-apoptotic cell death characterized by the iron-dependent overproduction of lipid hydroperoxides, which can be inhibited by the antioxidant activity of the solute carrier family member 11 (SLC7A11/xCT), a component of the cystine/glutamate antiporter. Whether nuclear events participate in the regulation of ferroptosis is largely unknown. Here, we show that the levels of H2Bub1 are decreased during erastin-induced ferroptosis and that loss of H2Bub1 increases the cellular sensitivity to ferroptosis. H2Bub1 epigenetically activates the expression of SLC7A11. Additionally, we show that the tumor suppressor p53 negatively regulates H2Bub1 levels independently of p53's transcription factor activity by promoting the nuclear translocation of the deubiquitinase USP7. Moreover, our studies reveal that p53 decreases H2Bub1 occupancy on the SLC7A11 gene regulatory region and represses the expression of SLC7A11 during erastin treatment. These data not only suggest a noncanonical role of p53 in chromatin regulation but also link p53 to ferroptosis via an H2Bub1-mediated epigenetic pathway. Overall, our work uncovers a previously unappreciated epigenetic mechanism for the regulation of ferroptosis.
Assuntos
Epigênese Genética , Ferroptose , Histonas/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Ubiquitinação , Transporte Ativo do Núcleo Celular , Sistema y+ de Transporte de Aminoácidos/genética , Sistema y+ de Transporte de Aminoácidos/metabolismo , Linhagem Celular Tumoral , Núcleo Celular , Células HEK293 , HumanosRESUMO
Semen stains are the most important biological evidence when identifying the aggressor in sexual assault cases. Current detecting assays of semen stains species identification were not confirmative enough. In this study, we investigated the potential of species identification of semen stains by using attenuated total reflection (ATR) Fourier transform infrared (FTIR) spectroscopy combined with advanced chemometrics methods. The effect of substrates types and time since deposition (TSD) were considered in the study. A partial least squares-discriminant analysis (PLS-DA) classification model was established which demonstrated complete separation between human and other species (rabbit, dog, boar, bull, and ram). Validation was conducted which showed prediction abilities with 100% accuracy. Additionally, we found species identification could be achieved without sperm cells which proved ability of spectroscopic methods detecting the semen samples from the case of azoospermia. This work provides a powerful and practical tool for species identification of semen stains in real forensic casework.
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Genética Forense/métodos , Sêmen/química , Especificidade da Espécie , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Animais , Análise Discriminante , Humanos , Análise dos Mínimos Quadrados , Masculino , Análise de Componente PrincipalRESUMO
The identification of antemortem and postmortem fractures is a critical and challenging task for forensic researchers. Based on our preliminary studies, we explored whether the combination of Fourier transform infrared spectroscopy (FTIR) and chemometrics can identify antemortem and postmortem fractures in complex environments. The impacts of the four environments on the bone spectrum were analyzed by principal component analysis (PCA). It was found that the bone degradation rate in the submerged and ground surface (GS) environments was higher than that in the buried and constant temperature and moisture (CTM) environments. Additionally, the bone degradation rate in buried environment higher than that in the CTM environment. The average spectrum, PCA and partial least squares discriminant analysis (PLS-DA) results all revealed that there were significant differences between the antemortem fracture and the remaining three groups in a complex environment. Compared with the antemortem fracture, the antemortem fracture control (AFC) and postmortem fracture control (PFC) tended to be more similar to the postmortem fracture. According to the loading plot, amide I and amide II were the main components that contributed to the identification of the antemortem fracture, AFC, postmortem fracture, and PFC. Finally, we established a differential model for the antemortem and postmortem fractures (an accuracy of 96.9%), and a differentiation model for the antemortem fracture, AFC, postmortem fracture, and PFC (an accuracy of 87.5%). In conclusion, FTIR spectroscopy is a reliable tool for the identification of antemortem and postmortem fractures in complex environments.
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Meio Ambiente , Modelos Teóricos , Tíbia/química , Fraturas da Tíbia , Animais , Restos Mortais/química , Masculino , Modelos Animais , Mudanças Depois da Morte , Análise de Componente Principal , Coelhos , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
Microbes play an essential role in the decomposition process but were poorly understood in their succession and behaviour. Previous researches have shown that microbes show predictable behaviour that starts at death and changes during the decomposition process. Research of such behaviour enhances the understanding of decomposition and benefits estimating the postmortem interval (PMI) in forensic investigations, which is critical but faces multiple challenges. In this study, we combined microbial community characterization, microbiome sequencing from different organs (i.e. brain, heart and cecum) and machine learning algorithms [random forest (RF), support vector machine (SVM) and artificial neural network (ANN)] to investigate microbial succession pattern during corpse decomposition and estimate PMI in a mouse corpse system. Microbial communities exhibited significant differences between the death point and advanced decay stages. Enterococcus faecalis, Anaerosalibacter bizertensis, Lactobacillus reuteri, and so forth were identified as the most informative species in the decomposition process. Furthermore, the ANN model combined with the postmortem microbial data set from the cecum, which was the best combination among all candidates, yielded a mean absolute error of 1.5 ± 0.8 h within 24-h decomposition and 14.5 ± 4.4 h within 15-day decomposition. This integrated model can serve as a reliable and accurate technology in PMI estimation.
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Aprendizado de Máquina , Microbiota , Mudanças Depois da Morte , Animais , Bactérias/classificação , Bactérias/genética , Encéfalo/microbiologia , Ceco/microbiologia , Coração/microbiologia , Masculino , Camundongos Endogâmicos C57BLRESUMO
Substantial evidence has shown that elevated circulating corticosteroids or chronic stress contributes to neuronal cell death, cognitive and mental disorders. However, the underlying mechanism is still unclear. Taurine is considered to protect neuronal cells from apoptotic cell death in neurodegenerative diseases and neuropsychiatric disorders. In the present study, the protective effects of taurine against corticosterone (CORT)-induced oxidative damage in SK-N-SH neuronal cells were investigated. The results showed that CORT significantly induced cell death, which was blocked by pretreatment with taurine. Similarly, pretreatment with taurine suppressed CORT-induced apoptotic cell death decreasing the levels of intracellular reactive oxygen species and improving mitochondrial function. Pretreatment with taurine increased the expression of phosphorylated extracellular regulated protein kinases (ERK) as well as the nuclear translocation of nuclear factor (erythroid 2-derived)-like 2 (Nrf2) in the CORT rich environment. Furthermore, administration of the ERK inhibitor U0126 or transient (siRNA) silencing of Nrf2 blocked the protective effects of taurine on cell viability and expression levels of Nrf2 and heme oxygenase-1 (HO-1) in the CORT model of neuronal damage. These results suggest that the Nrf2 signaling pathway may play a role in the protection mechanism of taurine against CORT-induced neuronal oxidative damage.
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Antioxidantes/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Transdução de Sinais/efeitos dos fármacos , Taurina/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Corticosterona/metabolismo , Corticosterona/farmacologia , Humanos , Substâncias Protetoras/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismoRESUMO
Accumulation of amyloid-ß (Aß) in synaptic mitochondria is associated with mitochondrial and synaptic injury. The underlying mechanisms and strategies to eliminate Aß and rescue mitochondrial and synaptic defects remain elusive. Presequence protease (PreP), a mitochondrial peptidasome, is a novel mitochondrial Aß degrading enzyme. Here, we demonstrate for the first time that increased expression of active human PreP in cortical neurons attenuates Alzheimer disease's (AD)-like mitochondrial amyloid pathology and synaptic mitochondrial dysfunction, and suppresses mitochondrial oxidative stress. Notably, PreP-overexpressed AD mice show significant reduction in the production of proinflammatory mediators. Accordingly, increased neuronal PreP expression improves learning and memory and synaptic function in vivo AD mice, and alleviates Aß-mediated reduction of long-term potentiation (LTP). Our results provide in vivo evidence that PreP may play an important role in maintaining mitochondrial integrity and function by clearance and degradation of mitochondrial Aß along with the improvement in synaptic and behavioral function in AD mouse model. Thus, enhancing PreP activity/expression may be a new therapeutic avenue for treatment of AD.
Assuntos
Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Mitocôndrias/metabolismo , Neurônios/metabolismo , Agregação Patológica de Proteínas/metabolismo , Serina Endopeptidases/metabolismo , Sinapses/metabolismo , Doença de Alzheimer/fisiopatologia , Animais , Comportamento Animal , Células Cultivadas , Cognição , Modelos Animais de Doenças , Expressão Gênica , Mediadores da Inflamação/metabolismo , Camundongos , Camundongos Transgênicos , Estresse Oxidativo , Proteólise , Serina Endopeptidases/genéticaRESUMO
It is widely accepted that accumulation of extracellular glutamate mediates neuronal injuries in a number of neurological disorders via binding glutamate receptors. However, usage of the glutamate receptor antagonists aimed to prevent glutamate excitotoxicity is still controversial. As a polyphenol natural product, curcumin, has been implied multiple bioactivities. In this study, we explored whether the silent information regulator 1 (SIRT1)-peroxisome proliferator-activated receptor-coactivator 1α (PGC1α) pathway participated in the protection of curcumin against glutamate excitotoxicity. The cultured primary cortical neurons were treated with glutamate to set up a neuronal excitotoxicity model. The MTT and TUNEL methods were employed to measure cell viability and apoptosis, respectively. The mitochondrial function, the expression levels of SIRT1, PGC1α and acetylated PGC1α (ac-PGC1α) were measured to explore the mechanism of curcumin against glutamate excitotoxicity. The results showed that glutamate significantly induced cell death and apoptosis, which was blocked by pretreatment with curcumin. Meanwhile, curcumin preserved mitochondrial function, increased the expression level of SIRT1 and reduced the level of ac-PGC1α in the presence of glutamate. These results suggest that SIRT1-mediated deacetylation of PGC1α attributes to the neuroprotection of curcumin against glutamate excitotoxicity.
Assuntos
Córtex Cerebral/patologia , Curcumina/farmacologia , Ácido Glutâmico/toxicidade , Neurônios/patologia , Neurotoxinas/toxicidade , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Sirtuína 1/metabolismo , Acetilação/efeitos dos fármacos , Trifosfato de Adenosina/metabolismo , Animais , Benzamidas/farmacologia , Cálcio/metabolismo , Morte Celular/efeitos dos fármacos , Células Cultivadas , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Espaço Intracelular/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Naftóis/farmacologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neuroproteção/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismoRESUMO
Substantial evidence reveals that prenatal stress is closely linked with abnormal behavior in offspring, but the mechanism remains unclear. In this study, our aim was to observe the alterations of behaviors, metabotropic glutamate receptor-1/5 (mGluR1/5) and brain-derived neurotrophic factor (BDNF) in various brain regions of prenatally stressed offspring rats. The forced swimming test (FST) and the open field test (OFT) were carried on 1-month-old offspring rats. The expression levels of mGluR1, mGluR5, and BDNF mRNA were measured in various brain regions of the offspring rats. Our results showed that the immobile time in the FST was significantly increased in the late prenatal stress (LPS) group compared with that in the control group, especially in the female rats. Similarly, in the OFT, the rats in both the mid prenatal stress (MPS) and LPS groups demonstrated anxiety-like behavior, especially the male rats in the LPS group. The expression of mGluR1 protein was increased in the hippocampus and prefrontal cortex of rats from the LPS group, as well as in the prefrontal cortex of rats from the MPS group. Meanwhile, the expression of mGluR5 protein was facilitated in the hippocampus and prefrontal cortex of rats in the LPS group. The expression of mGluR5 protein was increased in the striatum of the female rats in both MPS and LPS groups, and only in the male rats from the LPS group. In addition, the reduced BDNF mRNA level was detected in the hippocampus and prefrontal cortex in the LPS rats, and in the striatum of the female rats in LPS group. These results indicate that alterations of the mGluR1, mGluR5 and BDNF mRNA may contribute to the depression-like and anxiety-like behaviors of prenatally stressed offspring rats.
Assuntos
Fator Neurotrófico Derivado do Encéfalo/biossíntese , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Receptor de Glutamato Metabotrópico 5/biossíntese , Receptores de Glutamato Metabotrópico/biossíntese , Estresse Psicológico/metabolismo , Animais , Ansiedade/metabolismo , Ansiedade/psicologia , Encéfalo/metabolismo , Depressão/metabolismo , Depressão/psicologia , Feminino , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/psicologia , Ratos , Ratos Sprague-Dawley , Estresse Psicológico/psicologiaRESUMO
As one of the most important hallmarks of Alzheimer's disease (AD), ß-amyloid (Aß) plays important roles in inducing reactive oxygen species (ROS) generation, mitochondrial dysfunction and apoptotic cell death in neurons. Curcumin extracted from the yellow pigments spice plant turmeric shows multiplied bioactivities such as antioxidant and anti-apoptosis properties in vitro and in vivo. In the present study, the neuroprotective effect of curcumin against Aß25-35-induced cell death in cultured cortical neurons was investigated. We found that pretreatment of curcumin prevented the cultured cortical neurons from Aß25-35-induced cell toxicity. In addition, curcumin improved mitochondrial membrane potential (ΔΨm), decreased ROS generation and inhibited apoptotic cell death in Aß25-35 treated neurons. Furthermore, we found that application of curcumin activated the expression of SIRT1 and subsequently decreased the expression of Bax in the presence of Aß25-35. The protective effect of curcumin was blocked by SIRT1 siRNA. Taken together, our results suggest that activation of SIRT1 is involved in the neuroprotective action of curcumin.
Assuntos
Peptídeos beta-Amiloides/toxicidade , Curcumina/farmacologia , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Fragmentos de Peptídeos/toxicidade , Sirtuína 1/metabolismo , Animais , Apoptose/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Células Cultivadas , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Síndromes Neurotóxicas , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Sirtuína 1/biossíntese , Proteína X Associada a bcl-2/biossínteseRESUMO
Amyloid ß (Aß) plays a critical role in the pathogenesis of Alzheimer disease (AD). Studies indicate that Aß causes reactive oxygen species (ROS) generation, mitochondrial dysfunction and neurons loss in vivo and in vitro. Taurine, a naturally occurring ß-amino acid in the brain, has been demonstrated to have neuroprotective properties. In the present study, the effects of taurine on cell viability and mitochondrial function in Aß1-42-treated SK-N-SH cells were investigated. Pretreatment of taurine significantly attenuated Aß1-42-induced neuronal death. Similarly, taurine suppressed the mPTP opening and reversed mitochondrial function in the presence of Aß1-42. Additionally, taurine attenuated the intracellular Ca(2+) and ROS generation induced by Aß1-42. Moreover, the expression of Sirtuin 1 (SIRT1) was obviously recovered by taurine in Aß1-42-treated SK-N-SH cells. Our results suggest that taurine prevents Aß1-42-induced mitochondrial dysfunction by activation of SIRT1. This study implies that taurine is a prospective additive for AD patients.
Assuntos
Peptídeos beta-Amiloides/metabolismo , Mitocôndrias/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Fragmentos de Peptídeos/metabolismo , Sirtuína 1/metabolismo , Taurina/farmacologia , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/farmacologia , Cálcio/metabolismo , Linhagem Celular Tumoral , Humanos , Mitocôndrias/metabolismo , Neurônios/metabolismo , Fragmentos de Peptídeos/farmacologia , RNA Interferente Pequeno/genética , Espécies Reativas de Oxigênio/metabolismo , Sirtuína 1/genéticaRESUMO
Traumatic lung injury (TLI), which is a common mechanical injury, is receiving increasing attention because of its serious hazards. In forensic practices, accurately identifying TLI is of great importance for investigations and case trials. The main goal of this research was to identify TLI utilizing attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy in combination with chemometrics. The macroscopic appearance of lung tissue showed that identifying TLI in lung tissue at the decomposition stage is not feasible by only visualization, and significant pulmonary hypostasis was observed in the lungs regardless of whether the lung tissue was injured. Average spectra and principal component analysis (PCA) suggested that the biochemical difference between injured lung tissue samples from the TLI group and noninjured lung tissue samples from the negative control group was mainly attributed to the different structures and contents of proteins. Partial least squares discriminant analysis (PLS-DA) was then utilized to identify TLI with an accuracy of 96.4% and 98.6% based on the training set and the test set, respectively. Next, we focused on samples that were misclassified in the model and proposed that the misclassification could be caused by the pulmonary hypostasis effect. Therefore, two additional PCA and PLS-DA models were created to identify the pulmonary hypostatic areas between the TLI group and the negative control group and the nonpulmonary hypostatic areas between the TLI group and the negative control group. The PCA results indicated that the biochemical difference between the two groups was still associated with proteins, and the two PLS-DA models achieved 100% accuracy based on both the training and test sets. This result indicated that when pulmonary hypostasis was considered and the lung tissue was divided into pulmonary hypostatic areas and nonpulmonary hypostatic areas for separate comparisons, TLI identification was achieved with a greater accuracy than that obtained when the two areas were combined. This research confirms that the combined application of ATR-FTIR spectroscopy and chemometrics can be utilized to accurately identify TLI.
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Lesão Pulmonar , Humanos , Lesão Pulmonar/diagnóstico , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Quimiometria , Análise Discriminante , Análise dos Mínimos Quadrados , Análise de Componente Principal , Pulmão , Proteínas Mutadas de Ataxia TelangiectasiaRESUMO
Background: Preeclampsia (PE) is a hypertensive disorder of pregnancy that threatens the lives of millions of pregnant women and their babies worldwide. Without effective medications, there are thousands of maternal and child mortalities every year. Resveratrol (RSV), a non-flavonoid polyphenol extracted from multiple plants, has shown positive effects in treating hypertension, cardiovascular disorders, and even PE. This study aimed to explore the pharmacological mechanism of RSV in treating PE by using network pharmacology and bioinformatics. Methods: With the use of multiple databases, 66 intersecting targets were obtained from the 347 putative targets of RSV and 526 PE-related genes. Then, Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were conducted to investigate the functions of the intersecting targets. The protein-protein interaction network and target-pathway network were drawn and analyzed to illustrate the correlation between targets and pathways. Finally, molecular docking was conducted to calculate the binding energy between RSV and core targets. Results: The results showed that the core targets of RSV were IL6, TNF, IL1B, VEGFA, STAT3, and EGFR. There existed good binding between RSV and IL6, TNF, IL1B, VEGFA, and EGFR. In addition, we found that RSV mainly functioned in the AGE-RAGE and HIF-1 signaling pathways, which are associated with the occurrence and development of PE. Conclusion: In conclusion, our findings indicated that RSV has the effects of regulating angiogenesis and anti-inflammation and can be a candidate medicine for treating PE.
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Hipertensão , Pré-Eclâmpsia , Gravidez , Lactente , Criança , Humanos , Feminino , Resveratrol/farmacologia , Resveratrol/uso terapêutico , Pré-Eclâmpsia/tratamento farmacológico , Interleucina-6 , Simulação de Acoplamento Molecular , Farmacologia em Rede , Fator 1 Induzível por Hipóxia , Receptores ErbBRESUMO
BACKGROUND: Alzheimer's disease (AD) is one of the most common neurodegenerative disorders in the world, but still lack of effective drug treatment. Gynostemma Pentaphyllum (Thunb.) Makino (GpM), a Chinese medicinal herb, plays important roles in anti-inflammation, anti-oxidative stress and anti-tumor, which has been reported to ameliorate cognitive impairment of AD. However, the neuroprotective mechanism of GpM remains unclear. This study aims to investigate the targets and possible signaling pathways of GpM in the treatment of AD. METHODS: Active compounds of GpM and their putative target proteins were selected from Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database and Analysis Platform. AD-associated targets were identified from GeneCards, the Online Mendelian Inheritance in Man (OMIM) database and the Therapeutic Target Database (TTD). The intersecting targets of GpM and AD were identified and Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were carried out to analyze the mechanism of them. Compound-target-pathway (CTP) network and protein-protein interaction (PPI) network were constructed and analyzed to elucidate the correlation between compounds, proteins and pathways. Molecular docking was performed to further demonstrate the possibility of GpM for AD. RESULTS: A total of 13 active compounds of GpM, 168 putative target proteins of compounds and 722 AD-associated targets were identified. Eighteen intersecting targets of GpM and AD were found and the epidermal growth factor receptor (EGFR), interleukin-1 beta (IL-1ß), interleukin-6 (IL-6), nitric oxide synthase in endothelial (NOS3) and serum paraoxonase/arylesterase 1 (PON1) were selected as the primary targets of GpM in the treatment of AD. The neuroprotective effect of GPM was related to a variety of pathways, including amoebiasis, HIF-1 signaling pathway, cytokine-cytokine receptor interaction and so on. CONCLUSIONS: Our findings elucidate the active compounds, targets and pathways of GpM involved in effects of anti-AD. The novel mechanism of GpM against AD provides more treatment options for AD.
Assuntos
Doença de Alzheimer , Medicamentos de Ervas Chinesas , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Arildialquilfosfatase/uso terapêutico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Gynostemma , Humanos , Simulação de Acoplamento Molecular , Farmacologia em Rede , NeuroproteçãoRESUMO
Different degrees of myocardial fibrosis can often be observed in sudden cardiac death cases, so that the identification of myocardial fibrosis is an important step in forensics to identify cardiac death. Previous methods are restricted by complex algorithms, high cost, low sensitivity and high requirements. Attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy is an efficient and rapid method to identify tissue types, which has been used increasingly in forensics. This study aims to identify novel biophysical biomarkers of myocardial fibrosis and establish a prediction model by using ATR-FTIR analysis combined with chemometrics. A total of 129 tissue blocks taken from human hearts were cut into slices, and then ATR-FTIR spectroscopy and hematoxylin and eosin (HE) staining were performed. By using HE staining, the samples were divided into the experimental group (with myocardial fibrosis) and the control group (without myocardial fibrosis). The chemometrics classification results showed that the sensitivity and specificity of the training dataset were 0.91 and 1.0 respectively, and the sensitivity and specificity of the predictive dataset were 0.862 and 0.900. This study demonstrated that ATR-FTIR spectroscopy combined with chemometrics is a novel method for identifying myocardial fibrosis.