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1.
Leg Med (Tokyo) ; 53: 101957, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34481193

RESUMO

The Microreader™ 19X Direct ID System was a newly developed multiplex PCR kit, which could detect 19 X-chromosomal STR loci (DXS6795, DXS9907, DXS6803, GATA172D05, DXS6807, GATA31E08, DXS7423, DXS6810, DXS101, DXS9902, DXS7133, DXS6800, DXS981, DXS10162, DXS6809, DXS10135, HPRTB, GATA165B12, DXS10079) and the sex determination locus of AMEL simultaneously. Different from other X-STR multiplex PCR kits, no linkage groups are included in this system, so the likelihood ratios could be calculated without the consideration of linkage groups. In this study, PCR conditions, sensitivity, species specificity, stability, DNA mixtures, concordance, stutter, sizing precision and population studies were conducted according to the SWGDAM developmental validation guidelines. The results indicated that this new X-STRs multiplex system was an efficient and reliable detection system, which could facilitate human kinship analysis and identification testing, as a powerful supplementary to autosomal STR kits.

2.
Cytokine ; 146: 155557, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34303273

RESUMO

AIM: Atrial fibrillation (AF) is a common clinical arrhythmia and can cause a variety of complications. To study the therapeutic effect of H2S in atrial fibrosis and explore the important role of miR-133a, in vitro experiments in human atrial fibroblasts (HAFs) were conducted. METHODS: The fibrosis in HAFs was induced by Ang II. The expression levels of miR-133a and CTGF in HAFs were examined by qRT-PCR. The proliferation and migration of HAFs were detected by CCK-8 and cell scratch assays. The protein expressions of CTGF, collagen I, collagen III and α-SMA were detected by western blotting. The dual-luciferase reporter gene was used to detect the interaction between miR-133a and CTGF. RESULTS: The proliferation and migration of HAFs stimulated by Ang II were enhanced, the expression of miR-133a was reduced, and the levels of CTGF and fibrosis markers (collagen I, collagen III and α-SMA) were increased. Furthermore, H2S reduced fibrosis, proliferation and migration of HAFs induced by Ang II. Accordingly, overexpression of miR-133a inhibited the proliferation and migration ability on Ang II-induced HAFs, and decreased the protein expressions of related fibrosis markers and CTGF. Meanwhile, miR-133a inhibitor could reverse the inhibition effect of H2S on proliferation and migration in HAFs by Ang II-induced. By targeting CTGF, miR-133a inhibited the expression of CTGF. CONCLUSION: H2S improved myocardial cell fibrosis by significantly increasing the expression of miR-133a, and CTGF might be a potential target for miR-133a to play an important role in myocardial fibrosis.

3.
Electrophoresis ; 42(16): 1578-1593, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34018209

RESUMO

The Y-STR landscape of Coastal Southeastern Han (CSEH) living in Chinese southeast areas (including Guangdong, Fujian, and Zhejiang provinces) is still unclear. We investigated 62 Y-STR markers in a reasonably large number of 1021 unrelated males and 1027 DNA-confirmed father-son pairs to broaden the genetic backgrounds of CSEH. In total, 85 null alleles, 121 off-ladder alleles, and 95 copy number variants were observed, and 1012 distinct haplotypes were determined with the overall HD and DC values of 0.999974 and 0.9912. We observed 369 mutations in 76 099 meiotic transfers, and the average estimated Y-STR mutation rate was 4.85 × 10-3 (95% CI, 4.4 × 10-3 -5.4 × 10-3 ). The Spearman correlation analyses indicated that GD values (R2 = 0.6548) and average allele sizes (R2 = 0.5989) have positive correlations with Y-STR mutation rates. Our RM Y-STR set including 8 candidate RM Y-STRs, of which DYS534, DYS630, and DYS713 are new candidates in CSEH, distinguished 18.52% of father-son pairs. This study also clarified the population structures of CSEH which isolated in population-mixed South China relatively. The strategy, SM Y-STRs for familial searching and RM Y-STRs for individual identification regionally, could be applicable based on enough knowledge of the Y-STR mutability of different populations.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33797119

RESUMO

In this work, an organic/inorganic hybrid polymer containing siloxyl functional groups was synthesized and applied to encapsulate phase change materials (PCMs). Owing to the mild conditions of the hypercrosslinking reaction, which only requires the addition of a catalytic amount of aqueous alkaline solution, both organic and inorganic PCMs are tolerated. It is noteworthy that the initial homogeneous state of the reaction mixture allowed the ultimate encapsulation rate of the PCMs and the uniform blending of the third nano-additives with the aim of thermal conductivity enhancement. Further study reveals that the presence of this hybrid hydrophobic polymer in a phase change composite endows the latter with a unique self-cleaning property. This novel PCM encapsulation protocol is suitable for nanoparticles including carbon-based nanomaterials, metal oxide nanoparticles, and inorganic oxide nanoparticles. A thermal conductivity enhancement of 600 % was achieved along with 93.7 % light-to-thermal conversion efficiency with a latent heat of 180 J g-1 without leakage.

5.
Int J Legal Med ; 135(4): 1213-1224, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33594458

RESUMO

The human microbiome is expected to be a new and promising tool for classification of human epithelial materials. Vaginal fluids are one of the most common biological samples in forensic sexual assault cases, and its identification is crucial to accurately determine the nature of the case. With the development of molecular biology technologies, the concept of vaginal microflora in different physiological states, ethnic groups, and geography is constantly improved. In this study, we conducted high-throughput sequencing of the V3-V4 hypervariable regions of the 16S rRNA gene in vaginal samples from Henan, Guangdong, and Xinjiang populations, in an attempt to reveal more information about the vaginal microflora in different regions. The results showed that the bio-geographical factors might affect the relative abundance of some vaginal microflora, but there was no significant difference in the composition of dominant bacteria in the vagina, which was mainly composed of Lactobacillus and Gardnerella. However, prediction models based on the random forest algorithm suggested that we might be able to distinguish vaginal fluids from populations of different regions according to the species-level OTUs in low abundance. It is promising that microbiome-based methods could provide more personal information when being attempted to trace the origin of body fluids.


Assuntos
Genes de RNAr , Microbiota , RNA Ribossômico 16S/genética , Vagina/microbiologia , Algoritmos , Grupo com Ancestrais do Continente Asiático/genética , Bactérias/classificação , Bactérias/isolamento & purificação , Biomarcadores , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Análise de Sequência de RNA
6.
J Ethnopharmacol ; 270: 113816, 2021 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-33444723

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The well-known Chinese prescription, Xiaoyan Lidan Formula (XYLDF), possesses efficiency of heat-clearing, dampness-eliminating and jaundice-removing. It has long been used clinically for the treatment of hepatobiliary diseases due to intrahepatic cholestasis (IHC). However, the mechanism of XYLDF for its therapeutic effects remains elusive. AIM OF THE STUDY: The study aimed to explore the potential targets for liver protective mechanism of XYLDF based on network pharmacology and experimental assays in ANIT-induced cholestatic hepatic injury (CHI) in rats. MATERIALS AND METHODS: On the basis of the 29 serum migrant compounds of XYLDF elucidated by UPLC-TOF-MS/MS, a network pharmacology approach was applied for the mechanism prediction. Systematic networks were constructed to identify potential molecular targets, biological processes, and signaling pathways. And the interactions between significantly potential targets and active compounds were simulated by molecular docking. For the mechanism validation, an ANIT-induced rat model was used to evaluate the effects of XYLDF on CHI according to serum biochemistry, bile flow rates, histopathological examination, and the gene and protein expression including enzymes related to synthesis, export, and import of bile acid in liver and ileum, and those of inflammatory cytokines, analyzed by RT-qPCR and WB. RESULTS: The results of network pharmacology research indicated TNF (TNF-α), RELA (NF-κB), NR1H4 (FXR), and ICAM1 (ICAM-1) to be the important potential targets of XYLDF for cholestatic liver injury, which are related to bile metabolism and NF-κB-mediated inflammatory signaling. And the molecular docking had pre-validated the prediction of network pharmacology, as the core active compounds of XYLDF had shown strong simulation binding affinity with FXR, followed by NF-κB, TNF-α, and ICAM-1. Meanwhile, the effects of XYLDF after oral administration on ANIT-induced CHI in rats exhibited the decreased levels of transaminases (ALT and AST), TBA, and TBIL in serum, raised bile flow rates, and markedly improved hepatic histopathology. Furthermore, consistent to the above targets prediction and molecular docking, XYLDF significantly up-regulated the expression of FXR, SHP, BSEP, and MRP2, and down-regulated CYP7A1 and NTCP in liver, and promoted expression of IBABP and OSTα/ß in ileum, suggesting the activation of FXR-mediated pathway referring to bile acid synthesis, transportation, and reabsorption. Moreover, the lower levels of TNF-α in plasma and liver, as well as the reduced hepatic gene and protein expression of NF-κB, TNF-α, and ICAM-1 after XYLDF treatment revealed the suppression of NF-κB-mediated inflammatory signaling pathway, as evidenced by the inhibition of nuclear translocation of NF-κB. CONCLUSIONS: XYLDF exhibited an ameliorative liver protective effect on ANIT-induced cholestatic hepatic injury. The present study has confirmed its mechanism as activating the FXR-regulated bile acid pathway and inhibiting inflammation via the NF-κB signaling pathway.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Colestase Intra-Hepática/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Redes e Vias Metabólicas/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Substâncias Protetoras/uso terapêutico , 1-Naftilisotiocianato/toxicidade , Animais , Ácidos e Sais Biliares/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/patologia , Colestase Intra-Hepática/sangue , Colestase Intra-Hepática/induzido quimicamente , Colestase Intra-Hepática/patologia , Modelos Animais de Doenças , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Masculino , Simulação de Acoplamento Molecular , NF-kappa B/metabolismo , Mapas de Interação de Proteínas/efeitos dos fármacos , Ratos Sprague-Dawley , Receptores Citoplasmáticos e Nucleares/química , Receptores Citoplasmáticos e Nucleares/metabolismo , Transdução de Sinais/efeitos dos fármacos
7.
Phytomedicine ; 82: 153438, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33422953

RESUMO

BACKGROUND: 5-Hydroxy-4-methoxycanthin-6-one (PQ-A) is the main active compound in Ramulus et Folium Picrasmae, a Chinese herbal medicine commonly used in colitis treatment. PURPOSE: To clarify PQ-A's role and mechanism in colitis treatment based on a non-targeted metabolomics study. METHODS: Rats with ulcerative colitis (UC) established with 4% dextran sulfate sodium (DSS) were orally treated with PQ-A. Body weight, disease activity index (DAI), colon length, biochemical parameters (MDA and SOD), and histopathological score in colon tissue were measured. A UPLC-Q-TOF-MS/MS approach-based metabolomics analysis was conducted to explore the underlying mechanisms of PQ-A in colitis treatment. Inflammatory cytokines (TNF-α, IL-1ß, IL-6, and IL-10) concentrations in serum and their protein levels in the colon were determined. CD3 and NF-κB/p65 immunohistochemistry in the colon was semi-quantified. The related protein or mRNA in IKK-NF-κB/p65 signaling pathway was measured by Western blotting or RT-PCR, respectively. Potential molecular interactions between PQ-A and NF-κB/p65 was predicted using DS 2.5 software. RESULTS: PQ-A significantly prevented body weight loss and colonic shortening in colitic rats, and reduced the DAI and histopathologic score as well. PQ-A decreased MDA levels in the UC rat serum and increased those of SOD. Metabolomics results revealed forty-nine differential metabolites as biomarkers of DSS-induced colitis, demonstrating that the path-mechanism of colitis involved the perturbation of eight metabolic pathways, including alpha-linolenic acid and linoleic acid metabolism, sphingolipid metabolism, retinol metabolism, bile acid metabolism, et al. Thirty-six biomarkers were especially reversed to normal-like levels by PQ-A via regulation of alpha-linolenic acid and linoleic acid metabolism, sphingolipid metabolism, and retinol metabolism, which effectively hinted the potential pharmacological mechanism of PQ-A related to NF-κB/p65 inflammatory signaling. Molecular docking results predicted high affinity interaction between PQ-A and NF-κB/p65, involving hydrogen-bond interactions at five amino acid residues, suggesting NF-κB/p65 as a target. PQ-A decreased TNF-α, IL-1ß, and IL-6 concentrations in serum and their protein levels in colon tissue in colitic rats. CD3, MYD88, p-IκBα, NF-κB/p65, and p-NF-κB/p65 expression levels decreased, whereas those of IKKß and IκBα increased in colitic tissue following PQ-A treatment. PQ-A strongly inhibited nuclear translocation of NF-κB/p65. CONCLUSIONS: We provide an overview of PQ-A's possible mechanism of action in colitis treatment based on serum non-targeted metabolomics. PQ-A treatment can protect rats against DSS-induced colitis by suppressing the NF-κB/p65 signaling pathway.


Assuntos
Carbolinas/química , Carbolinas/uso terapêutico , Colite/tratamento farmacológico , Sulfato de Dextrana/efeitos adversos , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição RelA/metabolismo , Animais , Biomarcadores/metabolismo , Colite/induzido quimicamente , Citocinas/metabolismo , Masculino , Metabolômica , Simulação de Acoplamento Molecular , Ratos , Espectrometria de Massas em Tandem
8.
Curr Eye Res ; 46(2): 232-238, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32757684

RESUMO

Purpose: This work aimed to investigate the influences of microRNA-340 (miR-340) on proliferation and apoptosis of retinoblastoma (RB) cells and explore its regulatory mechanism. MATERIALS AND METHODS: miR-340 mimic and inhibitor were applied for up-regulating or inhibiting the expression of miR-340 in RB cell lines. Then, CCK-8 and AnnexinV-FITC/PI staining were used to measure cell proliferation and apoptosis, respectively. After that, luciferase assay was performed to affirm the direct targets of miR-340. Furthermore, qRT-PCR and western blotting assay were carried out to detect the levels of miR-340 and KIF14. RESULTS: Our results indicated that the miR-340 was lowly expressed in RB cell lines, and up-regulation of miR-340 can decrease the proliferation and induce the apoptosis of RB cells. Moreover, we verified that miR-340 controls KIF14 expression, either directly or through a subsequent molecular cascade, and inversely related to its expression. The results obtained from the rescue assays presented that over-expression of KIF14 reversed the miR-340-mediated inhibition on malignant phenotype of RB cells. CONCLUSIONS: Overall, we proved that miR-340 can decrease the proliferation and increase the apoptosis of RB cells, and its function in RB cells was at least partially achieved via down-regulation of KIF14, prompting that miR-340 was expected to supply a new direction for clinical therapy of RB in the future.

9.
Int J Legal Med ; 135(1): 53-62, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32583081

RESUMO

The identification of biological traces provides vital evidence in forensic reconstruction at crime scenes, especially in sexual offences. Compared with traditional presumptive or confirmatory methods, the microbiome-based method has been proven to be of great value in body fluid identification. Mixture of body fluids or tissue is common in sexual assault cases; thus, it is essential to determine the sources of mixed samples. In this study, 60 samples consisting of skin, saliva, and a mixed model of saliva deposited on facial skin were collected from a population living in Guangdong. Through 16s rDNA high-throughput sequencing, we identified the predominant microbes in saliva samples, viz., Haemophilus parainfluenzae T3T1, Neisseria flava, Gemella haemolysans, Prevotella melaninogenica, and Actinomyces odontolyticus; in skin samples, Cutibacterium acnes and Corynebacterium tuberculostearicum were the predominant species. The microbial composition of the same body fluid or tissue is similar in different individuals. However, among different body fluids or tissue, the composition of microflora in saliva is more stable than that on skin. Additionally, the microbial community in the mixed model of saliva deposited on facial skin from the same and different individuals was clearly determined by the constituent fluids or tissue, apart from the differences among the donors. Overall, the microbiome-based method may have good potential as a tool for identifying single and mixed body fluid or tissue.

10.
Int J Legal Med ; 135(3): 755-760, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-32468171

RESUMO

In 2009, a violent murder occurred. Two victims, a 47-year-old mother and her 21-year-old daughter, were murdered at home. After importing the 20 autosomal STR loci and 27 Y-STR loci into a database, no hit had been found. In 2019, a person with a prior criminal record was matched in the national forensic Y-STR database. When increasing the number of detected Y-STR loci to 60, all loci of the bloodstain donor at the crime and the suspect were still found to be identical. With the combined calculation of multiple autosomal STR and kinship index, we were able to identify the perpetrator as a previously unknown illegitimate child of a large family and solved the case.


Assuntos
Manchas de Sangue , Cromossomos Humanos Y/genética , Impressões Digitais de DNA/métodos , Genética Forense , Loci Gênicos , Homicídio , Repetições de Microssatélites , Adoção , Família , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Adulto Jovem
11.
Oxid Med Cell Longev ; 2020: 7374086, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33274005

RESUMO

Chrysophanol, a primary active ingredient of Cassia mimosoides Linn or Rhei radix et rhizoma, has various pharmacological properties, including anticancer, antidiabetic, and anti-inflammatory, as well as blood lipid regulation. However, whether chrysophanol can mitigate obesity, and its underlying mechanisms remains unclear. This study investigated whether chrysophanol effects energy metabolism in high-fat diet- (HFD-) induced obese mice and fat-specific Sirtuin 6- (SIRT6-) knockout (FKO) mice, targeting the SIRT6/AMPK signaling pathway in brown and white fat tissue. Our results showed that chrysophanol can effectively inhibit lipid accumulation in vitro and reduce mice's body weight, improve insulin sensitivity and reduced fat content of mice, and induce energy consumption in HFD-induced obese mice by activating the SIRT6/AMPK pathway. However, a treatment with OSS-128167, an SIRT6 inhibitor, or si-SIRT6, SIRT6 target specific small interfering RNA, in vitro blocked chrysophanol inhibition of lipid accumulation. Similar results were obtained when blocking the AMPK pathway. Moreover, in the HFD-induced obese model with SIRT6 FKO mice, histological analysis and genetic test results showed that chrysophanol treatment did not reduce lipid droplets and upregulated the uncoupling protein 1 (UCP1) expression. Rather, it upregulated the expression of thermogenic genes and activated white fat breakdown by inducing phosphorylation of adenosine 5'-monophosphate- (AMP-) activated protein kinase (AMPK), both in vitro and in vivo. OSS-128167 or si-SIRT6 blocked chrysophanol's upregulation of peroxisome proliferator-activated receptor-γ coactivator-1α (Pgc-1α) and Ucp1 expression. In conclusion, this study demonstrated that chrysophanol can activate brown fat through the SIRT6/AMPK pathway and increase energy consumption, insulin sensitivity, and heat production, thereby alleviating obesity and metabolic disorders.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Adipócitos Marrons/metabolismo , Antraquinonas/farmacologia , Síndrome Metabólica/metabolismo , Transdução de Sinais/efeitos dos fármacos , Sirtuínas/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Animais , Masculino , Síndrome Metabólica/tratamento farmacológico , Síndrome Metabólica/genética , Síndrome Metabólica/patologia , Camundongos , Camundongos Knockout , Transdução de Sinais/genética , Sirtuínas/genética
12.
Gut ; 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-33257471

RESUMO

OBJECTIVE: Impaired hepatic fatty acids oxidation results in lipid accumulation and redox imbalance, promoting the development of fatty liver diseases and insulin resistance. However, the underlying pathogenic mechanism is poorly understood. Krüppel-like factor 16 (KLF16) is a transcription factor that abounds in liver. We explored whether and by what mechanisms KLF16 affects hepatic lipid catabolism to improve hepatosteatosis and insulin resistance. DESIGN: KLF16 expression was determined in patients with non-alcoholic fatty liver disease (NAFLD) and mice models. The role of KLF16 in the regulation of lipid metabolism was investigated using hepatocyte-specific KLF16-deficient mice fed a high-fat diet (HFD) or using an adenovirus/adeno-associated virus to alter KLF16 expression in mouse primary hepatocytes (MPHs) and in vivo livers. RNA-seq, luciferase reporter gene assay and ChIP analysis served to explore the molecular mechanisms involved. RESULTS: KLF16 expression was decreased in patients with NAFLD, mice models and oleic acid and palmitic acid (OA and PA) cochallenged hepatocytes. Hepatic KLF16 knockout impaired fatty acid oxidation, aggravated mitochondrial stress, ROS burden, advancing hepatic steatosis and insulin resistance. Conversely, KLF16 overexpression reduced lipid deposition and improved insulin resistance via directly binding the promoter of peroxisome proliferator-activated receptor α (PPARα) to accelerate fatty acids oxidation and attenuate mitochondrial stress, oxidative stress in db/db and HFD mice. PPARα deficiency diminished the KLF16-evoked protective effects against lipid deposition in MPHs. Hepatic-specific PPARα overexpression effectively rescued KLF16 deficiency-induced hepatic steatosis, altered redox balance and insulin resistance. CONCLUSIONS: These findings prove that a direct KLF16-PPARα pathway closely links hepatic lipid homeostasis and redox balance, whose dysfunction promotes insulin resistance and hepatic steatosis.

13.
Front Chem ; 8: 601636, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33304887

RESUMO

Determination of serum cholesterol (Chol) is important for disease diagnosis, and has attracted great attention during the last few decades. Herein, a new magnetic nanoparticle-based ligand replacement strategy has been presented for chemical luminescence detection of Chol. The detection depends on ligand replacement from ferrocene (Fc) to Chol through a ß-cyclodextrin (ß-CD)-based host-guest interaction, which releases Fc-Hemin as a catalyst for the luminol/hydrogen peroxide chemical luminescence system. More importantly, the luminescence signal can be captured by the camera of a smartphone, thus realizing Chol detection with less instrument dependency. The limit of detection of this method is calculated to be 0.18 µM, which is comparable to some of the developed methods. Moreover, this method has been used successfully to quantify Chol from serum samples with a simple extraction process.

14.
J Mater Chem B ; 8(48): 11001-11009, 2020 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-33225325

RESUMO

Ratiometric fluorescent sensors are powerful tools for quantitative analyses. However, gold nano-clusters (AuNCs) as typical fluorophores in ratiometric sensors have some disadvantages, such as low luminous efficiency. In this study, a highly sensitive ratiometric fluorescence sensor was fabricated by the combination of AuNCs and fluorescein (FL), and the photonic crystals (PhCs) were used to selectively enhance the fluorescence intensity of AuNCs. This fluorescence sensor was used for the sensitive detection of acetylcholinesterase (AChE) and its inhibitor paraoxon. AChE can catalyze the hydrolysis of acetylthiocholine (ATCh) to form thiocholine (TCh), which can induce the fluorescence quenching of AuNCs while having no obvious influence on the fluorescence intensity of FL. AChE can be determined in the range from 0.1 to 25 mU mL-1 with a limit of detection (LOD) of 0.027 mU mL-1, and paraoxon can be determined in the range of 0.06 to 60 ng mL-1 with a LOD 0.025 ng mL-1. This method, as a new way to selectively improve the fluorescence signal of one of the fluorophores in the ratiometric sensor, would be a promising strategy for the sensitive determination of AChE and its inhibitor.


Assuntos
Acetilcolinesterase/análise , Técnicas Biossensoriais/métodos , Inibidores da Colinesterase/análise , Ouro/química , Cristais Líquidos/química , Nanopartículas Metálicas/química , Fluorescência , Corantes Fluorescentes/síntese química , Fenômenos Ópticos
15.
Forensic Sci Int ; 314: 110417, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32702532

RESUMO

Semen is a common body fluid type in forensic sexual assault cases. It is of great significance to effectively identify semen for restoring the crime scene and determining the nature of the case. Nowadays, microbiome-based method shows as a promising tool for forensic body fluid identification. To explore the environmental impact on microbial community of semen and its traceability, 16S rDNA high-throughput sequencing was conducted to ten paired semen samples. Affected by exposure, the diversity of microbial community decreased generally as the genus Staphylococcus exhibited a relatively significant increase. However, the genus Staphylococcus, Corynebacterium, Corynebacterium_1 were observed in almost all 20 samples. Community barplot analysis and heatmap analysis showed composition of the predominant microbe in semen at the phyla and genus level maintained basically, so that it could distinguish from vaginal fluid and saliva regardless of environmental exposure. Based on these results, we believe the application of single microbial marker may limit in semen identification, but the method depending on microbial community might be useful for distinguishing semen even under indoor exposure.


Assuntos
Exposição Ambiental , Microbiota , Sêmen/microbiologia , Muco do Colo Uterino/microbiologia , Feminino , Medicina Legal , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Reação em Cadeia da Polimerase , RNA Ribossômico 16S/genética , Saliva/microbiologia
16.
Forensic Sci Int ; 314: 110370, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32682216

RESUMO

A case study involving an intentional homicide case in November 2018, in which the autosomal genotypes of the suspect were unavailable and only part of deletions of Y-STR loci were identified by Y-chromosomal typing. The suspect, male, was charged with beating the decedent, female, over the head with an iron water pipe to death. The use of standard autosomal DNA profiling to identify the suspect was unattainable due to the extensive volume blood of the decedent on the murder weapon which was inevitably cleaned by running water at the crime scene. As a result, autosomal genotypes of the suspect were unavailable and only partial samples of deletions of Y-STR loci were identified by Y-chromosomal typing. Y-STR analysis (Yfiler™ plus and AGCU Y36) was used on the collected DNA extracts and compared to reference samples of the suspect, as well as his father and brother in an attempt to positively identify the suspect as the perpetrator of the murder. Subsequent Y-STR genotyping for the suspect, his father and brother indicated that Y-STR genotype of the suspect was consistent with that discovered on the physical evidence and the deleted Y-STR loci were identical for both. No deletions of Y-STR genotype were observed in the suspect's father and brother. After changing a Y-STR kit, the deleted loci were still present in the suspect. In Addition, sequencing of the whole Y-chromosomal genes was performed on the samples taken from the suspect and his father and brother. Segmental deletions at Yq 11.222-Yq 11.23 of the suspect were observed and the deleted Y-STR markers were right on the deleted Y-chromosomal segments. In this case, although the suspect could not be identified by the autosomal STR profiles detected on the physical evidence, the discovery of identical Y-STR genotype and the identical deletions of Y-chromosomal segments made it plausible that DNA on the murder weapon was left behind by the suspect. This case study shows that in criminal cases like this, where the autosomal STR evidence is unattainable, Y-STR evidence can be used effectively as a substitute to identify the suspect.


Assuntos
Deleção Cromossômica , Cromossomos Humanos Y , Homicídio , Impressões Digitais de DNA , Feminino , Haplótipos , Humanos , Masculino , Repetições de Microssatélites , Reação em Cadeia da Polimerase
17.
J Pharm Pharmacol ; 72(12): 1761-1770, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32363585

RESUMO

OBJECTIVES: This study aimed to investigate the existing form of 5-hydroxy-4-methoxycanthin-6-one (PQ-A) in vivo after oral administration and the effects on its pharmacokinetics and tissue distribution by colitis. METHODS: A rapid HPLC-MS/MS method was established to simultaneously determine PQ-A and its main metabolite, 1-methoxicabony-ß-carboline (PQ-B), in biological samples acquired from normal and dextran sodium sulfate (DSS)-induced colitic rats administered orally with PQ-A. Then, the pharmacokinetics of both PQ-A and PQ-B, and tissue distribution of PQ-A in the above two states were analysed. KEY FINDINGS: The pharmacokinetic results showed that the prototype of PQ-A was the main existing form in both physiological and pathological conditions. And significant difference between the above two status in pharmacokinetics of PQ-A was observed, such as higher exposure and longer elimination in colitis than that in normal rats. It suggested that the pharmacokinetics of medications for colitis was affected by enteritis. The tissue distribution studies displayed that PQ-A mainly accumulated in intestinal tract. Especially, the distribution of PQ-A in intestinal tract was increased obviously in colitic rats. CONCLUSIONS: These results contributed to further illuminate the ADME process of PQ-A in different status and were prospected to be the reference to the clinical application of similar medicines in pathological states.

18.
Oxid Med Cell Longev ; 2020: 8026838, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32454943

RESUMO

Acetaminophen (APAP) toxicity leads to severe acute liver injury (ALI) by inducing excessive oxidative stress, inflammatory response, and hepatocyte apoptosis. Imperatorin (IMP) is a furanocoumarin from Angelica dahurica, which has antioxidant and anti-inflammatory effects. However, its potential to ameliorate ALI is unknown. In this study, APAP-treated genetic knockout of Farnesoid X receptor (FXR) and Sirtuin 1 (SIRT1) mice were used for research. The results revealed that IMP could improve the severity of liver injury and inhibit the increase of proinflammatory cytokines, oxidative damage, and apoptosis induced by overdose APAP in an FXR-dependent manner. We also found that IMP enhanced the activation and translocation of FXR by increasing the expression of SIRT1 and the phosphorylation of AMPK. Besides, single administration of IMP at 4 h after APAP injection can also improve necrotic areas and serum transaminase, indicating that IMP have both preventive and therapeutic effects. Taken together, it is the first time to demonstrate that IMP exerts protective effects against APAP overdose-induced hepatotoxicity by stimulating the SIRT1-FXR pathway. These findings suggest that IMP is a potential therapeutic candidate for ALI, offering promise for the treatment of hepatotoxicity associated with APAP overdose.


Assuntos
Acetaminofen/efeitos adversos , Overdose de Drogas/tratamento farmacológico , Furocumarinas/uso terapêutico , Fígado/lesões , Substâncias Protetoras/uso terapêutico , Doença Aguda , Animais , Antioxidantes/metabolismo , Citocinas/metabolismo , Overdose de Drogas/genética , Overdose de Drogas/patologia , Furocumarinas/química , Furocumarinas/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Hepatócitos/patologia , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos , Fígado/patologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Modelos Biológicos , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Receptores Citoplasmáticos e Nucleares/deficiência , Receptores Citoplasmáticos e Nucleares/metabolismo , Transdução de Sinais/efeitos dos fármacos , Sirtuína 1/metabolismo , Transcriptoma/genética , Regulação para Cima
19.
Mol Genet Genomics ; 295(4): 969-979, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32279092

RESUMO

The Tibetan-Yi Corridor, located on the eastern edge of the Tibetan Plateau, is the main route of the people of the plateau. Human settlement and diffusion along the corridor have played a pivotal role in shaping the genetic architecture of Sino-Tibetan-speaking (STs) populations in China. In this study, five STs groups (Chengdu Tibetan, Chengdu Han, Muli Tibetan, Lugu Lake Mosuo and Xichang Yi) settling in the Tibetan-Yi Corridor were genotyped via AGCU InDel 50 kit on the capillary electrophoresis platform to decrypt the genetic landscape and phylogenetic relationship of STs populations and investigate the forensic characteristics. Allele frequency distributions of all autosomal insertion/deletion polymorphisms (InDels) in studied groups comply with Hardy-Weinberg equilibrium. The combined power of discrimination values are 0.9999999999999999998, 0.9999999999999999995, 0.9999999999999999999, 0.999999999999999993 and 0.99999999999999999994, respectively, and all the combined probability of exclusion values exceed 0.9990. Forensically relevant statistics implied that these InDels could be used for individual identification and as a promising alternative to STR profiling in paternity testing. Typical population comparisons showed strikingly high homogeneity among studied STs people, indicating complicated genetic admixture among populations in the Tibetan-Yi Corridor. The STs groups in the Tibetan-Yi Corridor keep close genetic affinity with geographically or linguistically close populations, and the genetic components of investigated populations arose from a mixture of multiple ancestral gene pools (resulting from the admixture from the ancestral Highland Tibetans and ancestral Lowland indigenous populations).


Assuntos
Evolução Molecular , Genética Populacional , Mutação INDEL/genética , Filogenia , China/epidemiologia , Grupos Étnicos/genética , Feminino , Genética Forense/estatística & dados numéricos , Frequência do Gene , Humanos , Masculino , Polimorfismo Genético , Tibet/epidemiologia
20.
J Agric Food Chem ; 68(14): 4215-4226, 2020 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-32181656

RESUMO

Ginsenoside Rg2 has been previously reported to reduce glucose production and adipogenesis in adipose tissue. However, the effects of ginsenosides Rg2 on hepatic lipid metabolism remain vacant. In this study, we found that ginsenoside Rg2 treatment significantly attenuated oleic acid and palmitic acid (OA&PA)-induced intracellular lipid deposition and oxidative stress in mouse primary hepatocytes. C57BL/6J mice that are fed with a high-fat diet (HFD) and treated with ginsenosides Rg2 displayed decreased body weight, reversed hepatic steatosis, and improved glucose tolerance and insulin sensitivity. Ginsenoside Rg2 administration significantly ameliorated HFD-induced hepatic oxidative stress and apoptosis. Moreover, Ginsenoside Rg2 had a good affinity with Sirtuin1 (SIRT1) and regulated its expression in vivo and in vitro. Deficiency of SIRT1 eliminated the therapeutic effect of ginsenoside Rg2 on lipid accumulation and overproduction of reactive oxygen species (ROS) in OA&PA-induced mice primary hepatocytes. Ginsenoside Rg2 treatment failed to alter the lipid and glucose disorder in hepatic SIRT1 deficient mice feeding on HFD. SIRT1 deficiency dissolves the therapeutic effect of ginsenoside Rg2 on oxidative stress and hepatocyte apoptosis induced by HFD. In summary, ginsenoside Rg2 plays a therapeutic role in HFD-induced hepatosteatosis of mice by decreasing the lipogenesis process and improving antioxidant capacity in an SIRT1-dependent manner.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Ginsenosídeos/farmacologia , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Sirtuína 1/metabolismo , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Resistência à Insulina , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipogênese/efeitos dos fármacos , Fígado , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Ácido Oleico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ácido Palmítico/metabolismo
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