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1.
Anim Genet ; 52(5): 683-693, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34196982

RESUMO

Artificial selection is one of the major forces modifying the genetic composition of livestock populations. Identifying genes under selection could be useful to elucidate their impact on phenotypic variation. We aimed to identify genomic regions targeted by selection for dairy and pigmentation traits in Murciano-Granadina goats. Performance of a selection scan based on the integrated haplotype score test in a population of 1183 Murciano-Granadina goats resulted in the identification of 77 candidate genomic regions/SNPs. The most significant selective sweeps mapped to chromosomes 1 (69.86 Mb), 4 (41.80-49.95 Mb), 11 (65.74 Mb), 12 (31.24 and 52.51 Mb), 17 (34.76-37.67 Mb), 22 (31.75 Mb), and 26 (26.69-31.05 Mb). By using previously generated RNA-Seq data, we built a catalogue of 6414 genes that are differentially expressed across goat lactation (i.e. 78 days post-partum, early lactation; 216 days post-partum, late lactation; 285 days post-partum, dry period). Interestingly, 183 of these genes mapped to selective sweeps and several of them display functions related with lipid, protein, and carbohydrate metabolism, insulin signaling, cell proliferation, as well as mammary development and involution. Of particular interest are the CSN3 and CSN1S2 genes, which encode two major milk proteins. Additionally, we found three pigmentation genes (GLI3, MC1R, and MITF) co-localizing with selective sweeps. Performance of a genome-wide association study and Sanger sequencing and TaqMan genotyping experiments revealed that the c.801C>G (p.Cys267Trp) polymorphism in the melanocortin 1 receptor (MC1R) gene is the main determinant of the black (GG or GC genotypes) and brown (CC genotypes) colorations of Murciano-Granadina goats.


Assuntos
Cabras/genética , Lactação/genética , Pigmentação/genética , Seleção Genética , Animais , Cruzamento , Feminino , Estudos de Associação Genética/veterinária , Genética Populacional , Genoma , Haplótipos , Proteínas do Leite/genética , Fenótipo , Polimorfismo de Nucleotídeo Único , Espanha
2.
Fa Yi Xue Za Zhi ; 36(6): 801-806, 2020 Dec.
Artigo em Zh | MEDLINE | ID: mdl-33550729

RESUMO

ABSTRACT: Postmortem interval (PMI) estimation is one of the most important and difficult academic tasks in forensic sciences. Due to the influence of the corpse itself and the water environment, corpses in water have unique corruption phenomenon and laws. Based on the experience of traditional PMI studies of corpses on land, forensic practitioners across the world have proposed a variety of practical methods for estimating postmortem submersion interval (PMSI). This paper summarizes the literatures related to PMSI in recent years, and introduces methods to infer PMSI according to the phenomenon of corpses, the development of insects, the succession pattern of aquatic organisms, and the changes of other physical and chemical indexes of corpses, in order to provide some reference for the study of PMSI of corpses in water.


Assuntos
Imersão , Mudanças Depois da Morte , Animais , Autopsia , Cadáver , Medicina Legal
3.
Fa Yi Xue Za Zhi ; 36(1): 6-5, 2020 02.
Artigo em Zh, Inglês | MEDLINE | ID: mdl-32198985

RESUMO

Abstract: Autopsy is of great significance to the elucidation of the pathological changes, pathogeneses and causes of death of corona virus disease 2019 (COVID-19) and can provide theoretical basis for more scientific and accurate prevention and control of the outbreak. Based on related laws and regulations, such as the Law of the People's Republic of China on Prevention and Control of Infectious Diseases, the clinical manifestations and epidemiological characteristics of COVID-19, and the related guidelines on the prevention and control of the outbreak, combined with the practical work of forensic pathology examination, the Guide to the Forensic Pathology Practice on Death Cases Related to Corona Virus Disease 2019 (COVID-19) (Trial Draft) has been developed. This guide includes information on the background investigation of the cases, autopsy room requirements, personal prevention and protections, external examinations, autopsy, auxiliary examinations, and so on. This guide can be used as a reference by forensic and pathological examination institutions, as well as examination staff.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Pandemias , Pneumonia Viral , COVID-19 , China , Patologia Legal , Humanos , Guias de Prática Clínica como Assunto , SARS-CoV-2
4.
J Dairy Sci ; 102(6): 5230-5241, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30928270

RESUMO

The variation in the casein genes has a major impact on the milk composition of goats. Even though many casein polymorphisms have been identified so far, we do not know yet whether they are evolutionarily ancient (i.e., they existed before domestication) or young (i.e., they emerged after domestication). Herewith, we identified casein polymorphisms in a data set of 106 caprine whole-genome sequences corresponding to bezoars (Capra aegagrus, the ancestor of domestic goats) and 4 domestic goat (Capra hircus) populations from Europe, Africa, the Far East, and the Near East. Domestic and wild goat populations shared a substantial number of casein SNP, from 36.1% (CSN2) to 55.1% (CSN1S2). The comparison of casein variation among bezoars and the 4 domestic goat populations demonstrated that more than 50% of the casein SNP are shared by 2 or more populations, and 18 to 44% are shared by all populations. Moreover, the majority of casein alleles reported in domestic goats also segregate in the bezoar, including several alleles displaying significant associations with milk composition (e.g., the A/B alleles of the CSN1S1 and CSN3 genes, the A allele of the CSN2 gene). We conclude that much of the current diversity of the caprine casein genes comes from ancient standing variation segregating in the ancestor of modern domestic goats.


Assuntos
Caseínas/genética , Genômica , Cabras/genética , Polimorfismo Genético , Distribuição Animal , Animais , Evolução Biológica , Caseínas/química , Variação Genética , Cabras/fisiologia , Leite/química
5.
Fa Yi Xue Za Zhi ; 35(2): 171-177, 2019 Apr.
Artigo em Inglês, Zh | MEDLINE | ID: mdl-31135111

RESUMO

ABSTRACT: Pulmonary thromboembolism (PTE), which is caused by detachment of venous thrombosis, is a common cause of sudden death in forensic practice. In the cases which die of PTE after trauma or die of PTE during non-thrombosis disease hospitalization, forensic pathologists are required to analyze the time sequence between trauma or medical practice and venous thrombosis, and then analyze their causal relationship. This review summarizes the history of thrombus age estimation and recent advances in forensic medicine, and then gives a brief outlook for future research to provide reference for forensic identification of PTE and guide follow-up studies.


Assuntos
Determinação da Idade pelo Esqueleto , Patologia Legal/tendências , Embolia Pulmonar , Trombose Venosa , Morte Súbita , Medicina Legal , Humanos
6.
Fa Yi Xue Za Zhi ; 35(2): 136-142, 2019 Apr.
Artigo em Inglês, Zh | MEDLINE | ID: mdl-31135105

RESUMO

ABSTRACT: Objective To investigate the expression of cannabinoid type 2 receptor (CB2R) at different time points after brain contusion and its relationship with wound age of mice. Methods A mouse brain contusion model was established with PCI3000 Precision Cortical Impactor. Expression changes of CB2R around the injured area were detected with immunohistochemical staining, immunofluorescent staining and Western blotting at different time points. Results Immunohistochemical staining results showed that only a few cells in the cerebral cortex of the sham operated group had CB2R positive expression. The ratio of CB2R positive cells gradually increased after injury and reached the peak twice at 12 h and 7 d post-injury, followed by a decrease to the normal level 28 d post-injury. The results of Western blotting were consistent with the immunohistochemical staining results. Immunofluorescent staining demonstrated that the changes of the ratio of CB2R positive cells in neurons, CB2R positive cells in monocytes and CB2R positive cells in astrocytes to the total cell number showed a single peak pattern, which peaked at 12 h, 1 d and 7 d post-injury, respectively. Conclusion The expression of CB2R after brain contusion in neurons, monocytes and astrocytes in mice suggests that it is likely to be involved in the regulation of the biological functions of those cells. The changes in CB2R are time-dependent, which suggests its potential applicability as a biological indicator for wound age estimation of brain contusion in forensic practice.


Assuntos
Contusão Encefálica/metabolismo , Lesões Encefálicas , Músculo Esquelético/metabolismo , Receptor CB2 de Canabinoide/metabolismo , Cicatrização/fisiologia , Animais , Western Blotting , Patologia Legal , Camundongos , Músculo Esquelético/patologia , Receptores de Canabinoides , Fatores de Tempo
7.
Fa Yi Xue Za Zhi ; 35(3): 267-272, 2019 Jun.
Artigo em Inglês, Zh | MEDLINE | ID: mdl-31282618

RESUMO

ABSTRACT: Objective To observe the change pattern of pericyte number at different time periods after mice skeletal muscle contusion and discuss its role in wound age estimation. Methods A mice gastrocnemius muscle contusion model was established. The form and number changes of pericytes at 1, 3, 5, 7, 9, 14, and 28 d post-injury were detected by multiple immunofluorescence staining. Results Compared with the slender shape of pericytes in normal skeletal muscles, pericytes in the contusion area had increased volume, rounder form and a round nuclei. Part of pericytes were found to express satellite cell markers paired-box transcription factor (Pax7) or myoblast determination 1 (MyoD1). The changes of pericyte number in skeletal muscles after contusion were time-dependant, and showed unimodal distribution with the extension of wound age. In the central contusion area, the number of pericytes peaked at 5 d post-injury while in the peripheral contusion area, the number of pericytes peaked at 5 d and 7 d post-injury. Conclusion The number of pericytes in contusion area varies time-dependently after skeletal muscle contusion in mice and might be a reference index for muscle wound age estimation, and is involved in the repair and regeneration of skeletal muscle injury.


Assuntos
Contusões , Pericitos , Animais , Modelos Animais de Doenças , Camundongos , Músculo Esquelético , Ratos Sprague-Dawley
8.
Fa Yi Xue Za Zhi ; 35(3): 273-279, 2019 Jun.
Artigo em Inglês, Zh | MEDLINE | ID: mdl-31282619

RESUMO

ABSTRACT: Objective To observe the expression changes of nuclear factor-erythroid derived 2-related factors (Nrf2) in different cells at different time points after human cerebral cortex contusion, and to discuss its application in brain wound age estimation. Methods Thirty-six human brain tissues were selected, of which 6 were for control and 30 were cortical contusion at different time points post-injury, which were divided into 0-1 h, 3-6 h, 1-3 d, 5-7 d, and 10-14 d post-injury groups, with 6 cases in each group. Based on paraffin embedded sections, HE staining was used to observe the morphological changes post-injury, and double immunofluorescence staining was used to detect the expression of Nrf2 in neurons, astrocytes, and microglia. The number of positive cells was counted and statistical analysis was made. Results The number of neurons decreased 1-3 d post-injury. The expression of Nrf2 cells in neurons increased after injury, and the rate of positive cells peaked at 1-3 d post-injury. Glial cells were activated 1-3 d post-injury, and the activation peaked at 5-7 d post-injury. The cerebromalacia began to form at 10-14 d post-injury. Glial fibrillary acidic protein (GFAP) positive cells in mice increased gradually after injury and peaked at 5-7 d post-injury, while the proportion of Nrf2 in GFAP positive cells was relatively stable. After injury, ionized calcium-binding adapter molecule 1 (IBA1) positive cells increased and activated gradually. The expression proportion of Nrf2 in IBA1 positive cells increased gradually, reached its peak at 5-7 d post-injury, and then decreased. Conclusion The expression of Nrf2 in different cells involves in the biological function of different cells post-injury, and the dynamic expression of single cells has a time-dependent pattern. This may provide a new reference index for the wound age estimation of brain contusion in human.


Assuntos
Contusão Encefálica , Animais , Córtex Cerebral , Proteína Glial Fibrilar Ácida , Humanos , Camundongos , Fator 2 Relacionado a NF-E2
9.
Fa Yi Xue Za Zhi ; 35(3): 280-284, 2019 Jun.
Artigo em Inglês, Zh | MEDLINE | ID: mdl-31282620

RESUMO

ABSTRACT: Objective To investigate the morphological changes in the degeneration and regeneration of neuromuscular junctions (NMJ) during the repair of mouse skeletal muscle contusion and discuss the correlation between the degeneration and regeneration of NMJ and wound age. Methods A total of 50 healthy adult male mice were randomly divided into 10 groups, including 9 experimental groups and 1 control group. Immunofluorescent staining was applied, and neurofilament was marked with neurofilament protein-H (NF-H), presynaptic membrane was marked with synaptophysin (Syn), presynaptic membrane was marked with acetylcholine receptor (AChR). Morphological changes of NMJ regeneration at different time points after mouse skeletal muscle contusion were detected. Results The neurofilament and presynaptic membrane of NMJ at the junction of contusion zones began to degrade after contusion, and completed degradation at about 3 d post-injury. Then they gradually regenerated, roughly completing the regeneration at about 21 d and basically reaching the control group level. The ratio of presynaptic membrane quantity to presynaptic membrane quantity showed a trend of decreasing then rising and finally reaching the control level. Conclusion During the repair of mouse skeletal muscle contusion, the morphological changes and wound age of the NMJ at the junction of contusion zones have a close correlation, which is expected to be one of the biological indicators for forensic skeletal muscle wound age estimation.


Assuntos
Contusões , Junção Neuromuscular , Animais , Masculino , Camundongos , Músculo Esquelético , Regeneração
10.
Fa Yi Xue Za Zhi ; 35(6): 651-656, 2019 Dec.
Artigo em Inglês, Zh | MEDLINE | ID: mdl-31970949

RESUMO

ABSTRACT: Objective To investigate the differences of heart mass and lung mass in forensic autopsy cases and to explore their application value in forensic identification. Methods The data from 1 614 autopsy cases accepted by center of Medico-legal Investigation of China Medical University between 2007 to 2016 were collected. The correlation of heart and lung mass with age, height, body weight, and body mass index (BMI), as well as differences in different causes of death were analyzed by GraphPad Prism 6.0 software. Results The heart mass and lung mass of males were higher than those of females (P<0.05). The heart mass of males and females was positively correlated with age, height, body weight and body mass index (BMI) (P<0.05). The heart mass of patients dying from sudden cardiac death (SCD) was significantly higher than those dying from other causes of death. The lung mass of patients dying from drowning and delayed treatment was higher than those dying from other causes of death (P<0.05). Conclusion In forensic practice, measurement of the heart mass and lung mass has certain significance for differential diagnosis and diagnosis of different causes of death.


Assuntos
Patologia Legal , Coração , Pulmão , Autopsia , Causas de Morte , China , Morte Súbita Cardíaca , Feminino , Coração/anatomia & histologia , Humanos , Pulmão/anatomia & histologia , Masculino , Tamanho do Órgão
11.
J Biol Regul Homeost Agents ; 32(2): 225-231, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29685000

RESUMO

Cerebral small vessel disease (CSVD) is a leading cause of progressive decline of cognition and a major risk factor for stroke. Thymoquinone (TQ) is the major biological component of Nigella sativa (N. sativa) and its extracts. We explored the possible protective effect of TQ against CSVD in strokeprone spontaneously hypertensive SHRsp rats. Morris water maze and novel object recognition tests were conducted to evaluate memory and cognitive function. mRNA expression of inflammatory factors were determined and oxidative stress was evaluated. We showed that TQ markedly decreased the level of systolic blood pressure in SHRsp rats. TQ reduced the escape latency time and the time spent in the target quadrant in the Morris water maze test in SHRsp rats. TQ also decreased the time spent with the novel object in SHRsp rats in both short- and long-term memory tests. TQ markedly increased the capacity to distinguish between familiar objects and novel objects in the SHRsp rats in the short- and long-term memory tests. The mRNA expression of IL-1ß, IL-6, monocyte chemoattractant protein-1 and cyclooxygenase-2 in the brain of SHRsp rats was remarkably decreased by TQ, indicating the reduction of inflammation. Moreover, TQ increased the activities of superoxide dismutase and catalase, decreased the malondialdehyde level and increased glutathione level in the brain of SHRsp rats, indicating the attenuation of oxidative stress. In summary, we found that TQ could effectively attenuate the blood pressure and the injury of memory and cognition under the condition of CSVD. The anti-inflammatory and antioxidant activities of TQ may be responsible for its protective effect. We demonstrate that TQ is a novel candidate for the treatment of CSVD and its neurological outcome.


Assuntos
Antioxidantes/farmacologia , Benzoquinonas/farmacologia , Encéfalo/efeitos dos fármacos , Doenças de Pequenos Vasos Cerebrais , Estresse Oxidativo/efeitos dos fármacos , Animais , Anti-Inflamatórios/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Ratos , Ratos Endogâmicos SHR
12.
Neoplasma ; 64(2): 175-181, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28043143

RESUMO

Current treatments for high-grade cervical intraepithelial neoplasia (CIN) and persistent infection with high-risk human papillomavirus (HR-HPV) type are mainly surgical interventions. However, such treatments are associated with adverse side effects and pose risks for future pregnancies. In order to reduce the requirement for excisional procedures, an effective and noninvasive therapy is needed for women at reproductive age. ALA-PDT has proved to be effective in the treatment of HPV-associated disease in several clinical investigations. In this study, the anti-proliferative effect of ALA-PDT was investigated in HPV16-immortalized cervical epithelial H8 cells. CCK-8 assay was used to measure cytotoxicity in H8 cells. The IC50 of ALA-PDT on H8 cells was about 120.75 ± 1.18 µM. We have now evaluated the mechanism by which ALA-PDT induces cell death. Annexin V-FITC/PI staining showed a significant dose-dependent induction of apoptosis by ALA-PDT in H8 cells, associated with accumulation of the tumor suppressor protein p53 and the cyclin-dependent kinase inhibitor p21. Furthermore, ALA-PDT down-regulates expression of HPV E6/E7 oncogene as well as up-regulate tumor suppressor RbAp48 protein. Together, our data provides a basis for understanding and developing ALA-PDT as a cure for HPV infection-associated diseases and prevention of cervical cancer.


Assuntos
Ácido Aminolevulínico/farmacologia , Células Epiteliais/efeitos dos fármacos , Fotoquimioterapia , Linhagem Celular , Células Epiteliais/virologia , Feminino , Papillomavirus Humano 16 , Humanos , Proteínas Oncogênicas Virais/genética , Proteínas Oncogênicas Virais/metabolismo , Proteínas E7 de Papillomavirus/genética , Proteínas E7 de Papillomavirus/metabolismo , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/tratamento farmacológico , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Proteína 4 de Ligação ao Retinoblastoma/genética , Proteína 4 de Ligação ao Retinoblastoma/metabolismo , Neoplasias do Colo do Útero/tratamento farmacológico , Displasia do Colo do Útero/tratamento farmacológico
13.
Fa Yi Xue Za Zhi ; 33(5): 482-485, 2017 Oct.
Artigo em Zh | MEDLINE | ID: mdl-29275552

RESUMO

OBJECTIVES: To analyse the cases of sudden death due to hyperthyroid heart disease, and explore the general information of deaths and the forensic pathological characteristics to provide reference evidence for forensic identification of such cases. METHODS: Six cases of sudden death due to hyperthyroid heart disease between 2001 and 2016 were selected from School of Forensic Medicine, China Medical University. The general information (gender and age), clinical manifestations, medical history, anatomical and histopathological findings, biochemical parameters and cause of death were analysed retrospectively. RESULTS: Most of the 6 patients had definite history of hyperthyroidism, and they all showed certain degrees of symptoms of cardiovascular disease; had obvious incentive factors of death; histopathological examination of thyroid conformed to the performances of diffuse toxic goiter; with increase of cardiac weight, dilatation of cardiac chambers, myocardial hypertrophy and focal necrosis; postmortem biochemical analyses of pericardial fluid could be used as an additional method for diagnostic of sudden death due to hyperthyroid heart disease. CONCLUSIONS: The identification of death due to hyperthyroid heart disease should be based on the clinical history and the results of autopsy, histopathological examination, postmortem toxicology tests. The postmortem biochemical detection of thyroid and cardiac function should be performed if necessary.


Assuntos
Autopsia , Doenças Cardiovasculares/mortalidade , Morte Súbita/patologia , Patologia Legal , Hipertireoidismo/patologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/patologia , China/epidemiologia , Morte Súbita Cardíaca , Medicina Legal , Coração , Cardiopatias , Humanos , Hipertireoidismo/complicações
14.
Zhonghua Bing Li Xue Za Zhi ; 45(11): 748-754, 2016 Nov 08.
Artigo em Zh | MEDLINE | ID: mdl-27821228

RESUMO

Objective: To detect TOP2A protein expression and gene copy number alterations, and to analyze related clinical and pathological implications in pediatric neuroblastic tumors (NT). Methods: Immunohistochemistry was used to detect TOP2A protein expression. Fluorescence in situ hybridization (FISH) was used to detect numerical aberrations of TOP2A. Results: TOP2A protein was expressed in 59.1%(52/88) of cases, which was associated with differentiation (P=0.006), Ki-67 index (P<0.01) and MKI (P=0.001). Twenty-eight cases (35.0%, 28/88) showed TOP2A gene amplification, which was correlated with the age (P<0.01), clinical stage (P=0.028), high risk group (P=0.001), Ki-67 index (P=0.040) and differentiation (P=0.014). Survival analysis showed that TOP2A expression was related to survival rate. Multivariate analyses showed that TOP2A expression was an independent predictor for poor prognosis (P=0.010). Conclusions: More than half of the cases show TOP2A expression, which is more likely associated with NB, high Ki-67 index and high MKI. Cases with TOP2A expression have shorter survivals and poorer prognosis. TOP2A amplification is seen in 35% and likely occurs in patients older than 18 months and at advanced INSS stages (Ⅲ and Ⅳ). As a target of the anthracycline-based adjuvant drugs, TOP2A test can be used to select patient with NT for the therapy.


Assuntos
Antígenos de Neoplasias/genética , DNA Topoisomerases Tipo II/genética , Proteínas de Ligação a DNA/genética , Amplificação de Genes , Dosagem de Genes , Neoplasias/genética , Neuroblastoma/genética , Fatores Etários , Antígenos de Neoplasias/metabolismo , Neoplasias da Mama , Variações do Número de Cópias de DNA , DNA Topoisomerases Tipo II/metabolismo , Proteínas de Ligação a DNA/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Lactente , Neoplasias/metabolismo , Neoplasias/patologia , Neuroblastoma/metabolismo , Neuroblastoma/mortalidade , Neuroblastoma/patologia , Proteínas de Ligação a Poli-ADP-Ribose , Análise de Sobrevida
15.
Nan Fang Yi Ke Da Xue Xue Bao ; 44(8): 1508-1517, 2024 Aug 20.
Artigo em Zh | MEDLINE | ID: mdl-39276046

RESUMO

OBJECTIVE: To analyze the core functional component groups (CFCG) in Yinchenhao Decoction (YCHD) and their possible pathways for treating hepatic fibrosis based on network pharmacology. METHODS: PPI data were extracted from DisGeNET, Genecards, CMGRN and PTHGRN to construct a weighted network using Cytoscape 3.9.1. The data of the chemical components in YCHD were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and the potential active components and targets were selected using PreADMET Web server and SwissTargetPrediction. A fusion model was constructed to obtain the functional effect space and evaluate the effective proteins to identify the CFCG followed by GO and KEGG pathway enrichment analyses for all the targets. In cultured human hepatic stellate cells (LX-2 cells), the cytotoxicity of different compounds in YCHD was tested using CCK-8 assay; the effects of these compounds on collagen α1 (Col1a1) mRNA expression and the pathways in 20 ng/mL TGF-ß1-stimulated cells were analyzed using RT-qPCR and Western blotting. RESULTS: A total of 1005 pathogenic genes, 226 potential active components and 1529 potential targets in YCHD and 52 potential targets of CFCG were obtained. Benzyl acetate, vanillic acid, clorius, polydatin, lauric acid and ferulic acid were selected for CCK-8 verification, and they all showed minimal cytotoxicity below the concentration of 200 µmol/L. Clorius, polydatin, lauric acid and ferulic acid all effectively inhibited TGF-ß1-induced LX-2 cell activation. At the concentration of 200 µmol/L, all these 4 components inhibited PI3K, p-PI3K, AKT, p-AKT, ERK, p-ERK, P38 MAPK and p-P38 MAPK expressions in TGF-ß1-induced LX-2 cells. CONCLUSION: The therapeutic effect of YCHD on hepatic fibrosis is probably mediated by its core functional components including benzyl acetate, vanillic acid, clorius, polydatin, lauric acid and ferulic acid, which inhibit the PI3K-AKT and MAPK pathways in hepatic stellate cells.


Assuntos
Medicamentos de Ervas Chinesas , Células Estreladas do Fígado , Cirrose Hepática , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/metabolismo , Células Estreladas do Fígado/efeitos dos fármacos , Células Estreladas do Fígado/metabolismo , Medicina Tradicional Chinesa/métodos , Fator de Crescimento Transformador beta1/metabolismo , Colágeno Tipo I/metabolismo , Colágeno Tipo I/genética , Ácidos Cumáricos/farmacologia , Linhagem Celular , Transdução de Sinais/efeitos dos fármacos , Farmacologia em Rede , Cadeia alfa 1 do Colágeno Tipo I
16.
J Prev Alzheimers Dis ; 11(5): 1348-1354, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39350380

RESUMO

BACKGROUND: There has been little direct examination of how traumatic brain injury (TBI) affects the rate of neurodegeneration for individuals with Alzheimer's disease (AD). METHODS: The study examined 89 cognitively normal adults (65 with and 24 without prior TBI) and 65 with AD (16 with and 49 without prior TBI). Cortical thickness was quantified from T1-weighted MRI scans at baseline and follow-up (mean interval 33.4 months). Partial least squares analysis was used to evaluate the effects of AD and TBI history on the longitudinal change in cortical thickness. RESULTS: Significant group effects were identified throughout the frontal and temporal cortices. Comparison of the AD groups to their control cohorts showed greater relative atrophy for the AD cohort with prior TBI. CONCLUSION: These results indicate that a history of TBI exacerbates longitudinal declines in cortical thickness among AD patients, providing new insights into the shared pathomechanisms between these neurological conditions.


Assuntos
Doença de Alzheimer , Lesões Encefálicas Traumáticas , Imageamento por Ressonância Magnética , Humanos , Doença de Alzheimer/patologia , Doença de Alzheimer/diagnóstico por imagem , Lesões Encefálicas Traumáticas/diagnóstico por imagem , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/patologia , Masculino , Feminino , Idoso , Estudos Longitudinais , Córtex Cerebral/patologia , Córtex Cerebral/diagnóstico por imagem , Atrofia , Pessoa de Meia-Idade , Espessura Cortical do Cérebro , Idoso de 80 Anos ou mais
17.
SAR QSAR Environ Res ; 34(12): 983-1001, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38047445

RESUMO

Quantitative structure-activity relationship (QSAR) models are powerful in silico tools for predicting the mutagenicity of unstable compounds, impurities and metabolites that are difficult to examine using the Ames test. Ideally, Ames/QSAR models for regulatory use should demonstrate high sensitivity, low false-negative rate and wide coverage of chemical space. To promote superior model development, the Division of Genetics and Mutagenesis, National Institute of Health Sciences, Japan (DGM/NIHS), conducted the Second Ames/QSAR International Challenge Project (2020-2022) as a successor to the First Project (2014-2017), with 21 teams from 11 countries participating. The DGM/NIHS provided a curated training dataset of approximately 12,000 chemicals and a trial dataset of approximately 1,600 chemicals, and each participating team predicted the Ames mutagenicity of each trial chemical using various Ames/QSAR models. The DGM/NIHS then provided the Ames test results for trial chemicals to assist in model improvement. Although overall model performance on the Second Project was not superior to that on the First, models from the eight teams participating in both projects achieved higher sensitivity than models from teams participating in only the Second Project. Thus, these evaluations have facilitated the development of QSAR models.


Assuntos
Mutagênicos , Relação Quantitativa Estrutura-Atividade , Mutagênicos/toxicidade , Mutagênicos/química , Testes de Mutagenicidade , Mutagênese , Japão
18.
Acta Biomater ; 141: 466-480, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-35063707

RESUMO

Ti-6Al-4V has been used as a surgical implant material for a long time because of its combination of strength, corrosion resistance and biocompatibility. However, there remains much that is not understood about how the surface reacts with the environment under tribocorrosion conditions. In particular, the conditions under which tribofilms form and their role on friction and wear are not clear. To evaluate the complicated nature of the dynamic surface microstructural changes on the wear track, high resolution transmission electron microscopy (TEM), scanning transmission electron microscope (STEM) and electron energy loss spectroscopy (EELS) have been used to characterise the structure and chemical composition of the tribofilm. Detailed analysis of the formation and structure of the tribofilm and the metal surface deformation behaviour were studied as a function of applied potential and the role of proteins in the lubricant. For the first time, graphitic and onion-like carbon structures from wear debris were found in the testing solution. The presence of carbon nanostructures in the tribocorrosion process and the formation of the tribofilm leads to an improved tribocorrosion behaviour of the system, in particular a reduction in wear and friction. A detailed, quantitative, analysis of surface deformation was undertaken, in particular, the geometrically necessary dislocation (GND) density was quantified using precession electron diffraction (PET). A clear correlation between applied potential, tribofilm formation and the surface strain was established. STATEMENT OF SIGNIFICANCE: The formation of tribofilm and microstructure modification of the Ti-6Al-4V surface during tribocorrosion in a physiological environment is not fully understood. In particular, the correlation between microstructural changes and electrochemical conditions is not clear. This study presents a detailed investigation of the structure and chemical composition of tribofilms at the nanoscale during tribocorrosion tests in simulated body fluid and gives a detailed and quantitative description of the evolved surface structure. A clear correlation between applied potential, tribofilm formation and the surface strain was established. Moreover, particular attention is paid to the wear debris particles captured from the lubricating solution, including nanocarbon onion structures. The implications for tribocorrosion of the alloy in its performance as an implant are discussed.


Assuntos
Líquidos Corporais , Titânio , Ligas , Carbono , Corrosão , Teste de Materiais , Propriedades de Superfície
19.
J Prev Alzheimers Dis ; 9(4): 692-700, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36281673

RESUMO

BACKGROUND: Frailty has been associated with cognitive markers of dementia but its relationship with behavioral markers of dementia are poorly understood. OBJECTIVES: To investigate the association between frailty and mild behavioral impairment (MBI), and whether this association is moderated by sex. DESIGN: Cross-sectional observational study. PARTICIPANTS/SETTING: 219 non-dementia participants (cognitively normal and mild cognitive impairment) from the Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS-ND) study. MEASUREMENTS: Frailty was measured using the frailty index (FI) with higher scores indicating more health deficits/greater frailty. MBI symptoms were derived from Neuropsychiatric Inventory Questionnaire scores using a published algorithm with a cut-off of >0 indicating MBI symptom presence and higher scores indicating greater severity. Multivariable logistic and linear regressions adjusted for age, sex, education, and cognitive diagnosis were used to test the association between FI and MBI symptom presence and severity, respectively, with MBI as the outcome variable. An FI-by-sex interaction term was included to test for sex-dependent effects. RESULTS: The FI mean and SD across the entire cohort was 0.14 ± 0.06 (median = 0.14, IQR = 0.09-0.17, range = 0.02-0.38). Higher FI scores were associated with the presence of MBI symptoms both globally and in the domains of decreased motivation, affective dysregulation, and psychosis. Higher FI scores were also associated with more severe MBI symptoms in a sex-dependent manner: both sexes reported similarly low MBI symptom severity at low (-1 SD) levels of FI but males reported 1.9x higher MBI symptom severity relative to females at high (+1 SD) levels of FI. CONCLUSIONS: The FI is associated with both the presence and severity of MBI, especially for males. This suggests that screening for early dementia risk should incorporate assessments of MBI for patients with frailty, and assessments of frailty for patients with MBI.


Assuntos
Disfunção Cognitiva , Fragilidade , Masculino , Feminino , Humanos , Testes Neuropsicológicos , Fragilidade/diagnóstico , Fragilidade/complicações , Estudos Transversais , Disfunção Cognitiva/diagnóstico
20.
iScience ; 25(6): 104460, 2022 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-35707724

RESUMO

Air pollution seriously threatens human health, and its consequences are particularly prevalent among environmentally vulnerable or sensitive groups. However, whether the concerns among these groups are different and how they affect air pollution governance remain unclear. Here, we extract 3.8 million haze-related posts from China's Sina Weibo and analyze the concerns raised by these groups by constructing an air pollution notability index. The results show that protection is the key theme for women aged 20-35 years, while elderly individuals are easily influenced by haze-related product ads yet lack awareness of scientific-based protection. Concerns shared by young individuals are more effective in pressuring the government in cities that experience higher levels of pollution. Concerns shared by women are more effective in cities that experience lower levels of pollution. This study evidences the influence of the public concerns conveyed via social media on air pollution governance in China.

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