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1.
Int J Legal Med ; 137(5): 1527-1533, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37493764

RESUMO

Radiology plays a crucial role in forensic anthropology for age estimation. However, most studies rely on morphological methods. This study aims to investigate the feasibility of using pubic bone mineral density (BMD) as a new age estimation method in the Chinese population. 468 pubic bone CT scans from living individuals in a Chinese hospital aged 18 to 87 years old were used to measure pubic BMD. The BMD of the bilateral pubic bone was measured using the Mimics software on cross-sectional CT images and the mean BMD of the bilateral pubic bone was also calculated. Regression analysis was performed to assess the correlation between pubic BMD and chronological age and to develop mathematical models for age estimation. We evaluated the accuracy of the best regression model using an independent validation sample by calculating the mean absolute error (MAE). Among all established models, the cubic regression model had the highest R2 value in both genders, with R2 = 0.550 for males and R2 = 0.634 for females. The results of the best model test showed that the MAE for predicting age using pubic BMD was 8.66 years in males and 7.69 years in females. This study highlights the potential of pubic BMD as a useful objective indicator for adult age estimation and could be used as an alternative in forensic practice when other better indicators are lacking.

2.
Int J Legal Med ; 136(3): 841-852, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35258670

RESUMO

OBJECTIVES: To assess the performance of knee MRI for forensic age prediction and classification for 12-, 14-, 16-, and 18-year thresholds. METHODS: The ossification stages of distal femoral epiphyses and proximal tibial epiphyses were assessed using an integrated staging system by Schmeling et al. and Kellinghaus et al. for knee 3.0T MRI with T1-weighted turbo spin-echo (T1-TSE) in sagittal orientation among 852 Chinese Han individuals (483 males and 369 females) aged 7-30 years. Regression models for age prediction were constructed and their performances were evaluated based on mean absolute deviation (MAD) values. In addition, the performances of age classification were assessed using receiver operating characteristic (ROC) analyses. RESULTS: The intra- and inter-observer agreement levels were very good (κ > 0.80). The complete fusion of those two types of epiphyses took place before 18.0 years in our study participants. The minimum MAD values were 2.51 years (distal femur) and 2.69 years (proximal tibia) in males, and 2.75 years (distal femur) and 2.87 years (proximal tibia) in females. The specificity values of constructed prediction models were all above 90% for the 12-, 14-, and 16-year thresholds, compared to the 74.8-84.6% for the 18-year threshold. Better performances of age prediction and classification were observed in males by distal femoral epiphyses. CONCLUSIONS: Ossification stages via 3.0T MRI of the knee with T1-TSE sequence using an integrated staging system could be a reliable noninvasive method for age prediction or for age classification for 12-, 14-, and 16-year thresholds, especially in males by distal femoral epiphyses. However, assessments based on the full bony fusion of the distal femoral epiphysis and proximal tibial epiphysis seemed not reliable for age classification for the 18-year threshold in the Chinese Han population.


Assuntos
Determinação da Idade pelo Esqueleto , Epífises , Determinação da Idade pelo Esqueleto/métodos , China , Epífises/diagnóstico por imagem , Feminino , Fêmur/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Osteogênese , Tíbia/diagnóstico por imagem
3.
Bioorg Med Chem ; 23(18): 6148-56, 2015 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-26304108

RESUMO

A series of novel salicylic acid derivatives containing metronidazole as Staphylococcus aureus Tyrosyl-tRNA synthetase (TyrRS) inhibitors have been synthesized and evaluated their biology activities as potential antibacterial agents. Among these compounds, compound 5r exhibited the most potent antibacterial activity against Gram-positive (S. aureus ATCC 6538 and Bacillus subtilis ATCC 6633) and Gram-negative (Escherichia coli ATCC 35218 and Pseudomonas aeruginosa ATCC 13525) with MICs of 0.39-1.57 µg/mL and showed the most potent S. aureus Tyrosyl-tRNA synthetase inhibitory with 2.3 µM. Docking simulation was performed to insert compound 5r into the crystal structure of S. aureus Tyrosyl-tRNA synthetase active site to determine the probable binding model. These results suggested that compound 5r may be a promising antibacterial agent.


Assuntos
Anti-Infecciosos/síntese química , Desenho de Fármacos , Metronidazol/química , Salicilatos/química , Anti-Infecciosos/química , Anti-Infecciosos/toxicidade , Sítios de Ligação , Cristalografia por Raios X , Eritrócitos/citologia , Eritrócitos/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Conformação Molecular , Simulação de Acoplamento Molecular , Estrutura Terciária de Proteína , Salicilatos/síntese química , Salicilatos/farmacologia , Staphylococcus aureus/enzimologia , Relação Estrutura-Atividade , Tirosina-tRNA Ligase/antagonistas & inibidores , Tirosina-tRNA Ligase/metabolismo
4.
Eur J Med Chem ; 251: 115214, 2023 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-36889252

RESUMO

CDK8 plays a key role in acute myeloid leukemia, colorectal cancer and other cancers. Here, a total of 54 compounds were designed and synthesized. Among them, the most potent one compound 43 (3-(1H-pyrrolo[2,3-b]pyridin-5-yl)benzamide), a novel CDK8 Ⅰ inhibitor, showed strong inhibitory activity against CDK8 (IC50 = 51.9 nM), good kinase selectivity, good anti AML cell proliferation activity (molm-13 GC50 = 1.57 ± 0.59 µM) and low toxicity in vivo (acute toxicity: 2000 mg/kg). Further mechanistic studies revealed that this compound could target CDK8 and then phosphorylate STAT-1 and STAT-5 thereby inhibiting of AML cell proliferation. In addition, compound 43 showed relatively good bioavailability (F = 28.00%) and could inhibit the growth of AML tumors in a dose-dependent manner in vivo. This study facilitates the further development of more potent CDK8 inhibitors for the treatment of the AML.


Assuntos
Antineoplásicos , Leucemia Mieloide Aguda , Humanos , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Linhagem Celular Tumoral , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/patologia , Proliferação de Células , Pirazóis/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Quinase 8 Dependente de Ciclina
5.
Anim Sci J ; 92(1): e13593, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34289202

RESUMO

To evaluate the effects of Spirulina platensis and probiotics on growth, immunity indexes, fecal flora, and fecal odor in mice, 40 mice were randomly allotted to four groups, and each was administrated with nothing, S. platensis, probiotics, or both for 28 days, respectively. Then, many indexes were measured. The results showed that S. platensis was more effective (P < 0.001) than probiotics in improving mice's feed conversion ration (FCR). In immunity, probiotics administration increased (P < 0.042) serum IgE, IgM, IFN-γ, colonic AHR, TLR4, and NF-κB protein expression and decreased (P < 0.039) serum IL-1α, IL-21, IL-22, and colonic ARNT gene expression. However, the S. platensis showed weaker effect, which increased (P < 0.025) the serum IgE, IgM, TNF-α, and the colonic AHR and NF-κB protein expression, and decreased (P < 0.01) serum IL-21. Probiotics consumption decreased the fecal odor by decreasing (P < 0.02) fecal Escherichia coli, indole-3-acetic acid (IAA), and skatole contents, and the S. platensis decreased (P = 0.04) the IAA. These results indicated that oral administration of probiotics, S. platensis, or both of them in mice probably benefited body's immunity and reduced fecal odor. However, their mechanisms were still unclear and need further study.


Assuntos
NF-kappa B , Odorantes , Probióticos , Spirulina , Administração Oral , Animais , Imunoglobulina E , Imunoglobulina M , Fatores Imunológicos , Camundongos
6.
Huan Jing Ke Xue ; 41(1): 313-320, 2020 Jan 08.
Artigo em Zh | MEDLINE | ID: mdl-31854932

RESUMO

Wastewater treatment plants hold a vast pool of antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs). The aim of this study is to analyze the ARB and ARGs in a pharmaceutical and chemical wastewater treatment plant using a metagenomic technique. The results of taxonomic annotation revealed that bacteria were the predominant domain. The most abundant phyla and genus was Proteobacteria and Hyphomicrobium, respectively. A total of 74 categories of ARGs were predicted using CARD with the most dominant types being sav 1866, dfrE, and mfd. Furthermore, a network analysis was conducted to investigate the co-occurrence patterns between ARGs and microbial taxa. ARGs were found to be highly connected to microbial taxa at the genus level. With respect to the antibiotic resistance mechanisms, antibiotic-specific efflux pumps appeared to be the most common mechanisms. Among these, resistance-nodulation-cell division (RND) was the major type. The most important functional pathway of this microbial community was metabolic correlation. Interestingly, there were many genes related to human diseases, among which bacterial infectious diseases were the main ones. On the one hand, these data further confirmed that pharmaceutical and chemical wastewater treatment plants are rich in ARB and ARGs. The accumulation of ARGs increases the potential environmental risks, and hence it is necessary to strengthen the active monitoring of ARB and ARGs in pharmaceutical and chemical wastewater treatment plants. On the other hand, research on ARB and ARGs offers important information for the selection of deep processing technology to effectively remove ARB and ARGs.


Assuntos
Bactérias/classificação , Farmacorresistência Bacteriana , Genes Bacterianos , Águas Residuárias , Purificação da Água , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Humanos , Metagenoma , Preparações Farmacêuticas
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