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1.
Front Endocrinol (Lausanne) ; 13: 874915, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35518933

RESUMO

Purpose: To assess the diverse cell populations of human corpus cavernosum in patients with severe erectile dysfunction (ED) at the single-cell level. Methods: Penile tissues collected from three patients were subjected to single-cell RNA sequencing using the BD Rhapsody™ platform. Common bioinformatics tools were used to analyze cellular heterogeneity and gene expression profiles from generated raw data, including the packages Seurat, Monocle, and CellPhoneDB. Results: Disease-related heterogeneity of cell types was determined in the cavernous tissue such as endothelial cells (ECs), smooth muscle cells, fibroblasts, and immune cells. Reclustering analysis of ECs identified an arteriole ECs subcluster and another one with gene signatures of fibroblasts. The proportion of fibroblasts was higher than the other cell populations and had the most significant cellular heterogeneity, in which a distinct subcluster co-expressed endothelial markers. The transition trajectory of differentiation from smooth muscle cells into fibroblasts was depicted using the pseudotime analysis, suggesting that the expansion of corpus cavernosum is possibly compromised as a result of fibrosis. Cell-cell communications among ECs, smooth muscle cells, fibroblasts, and macrophages were robust, which indicated that inflammation may also have a crucial role in the development of ED. Conclusions: Our study has demonstrated a comprehensive single-cell atlas of cellular components in human corpus cavernosum of ED, providing in-depth insights into the pathogenesis. Future research is warranted to explore disease-specific alterations for individualized treatment of ED.


Assuntos
Disfunção Erétil , Células Endoteliais , Disfunção Erétil/genética , Disfunção Erétil/patologia , Humanos , Masculino , Ereção Peniana/fisiologia , Pênis/patologia , Análise de Sequência de RNA
2.
Forensic Sci Int Genet ; 59: 102705, 2022 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-35462161

RESUMO

BACKGROUNDS: Y-chromosomal haplotypes based on Y-short tandem repeats (STRs) and Y-single nucleotide polymorphisms/insertion and deletion polymorphisms (SNPs/InDels) are used to characterize paternal lineages of unknown male trace donors. However, Y-chromosomal genetic markers are not currently sufficient for precise individual identification. Microhaplotype (MH), generally < 200 bp on autosomes and consisting of two or more SNPs, was recently introduced in forensic genetics with the development of massive parallel sequencing technology and may facilitate identification and DNA mixture deconvolution. Therefore, combining the two kinds of genetic markers may be beneficial in many forensic scenarios, especially crime scenes with male suspects, such as sexual assault cases. METHODS: In the present study, we developed a novel MPS-based panel, Microhaplotype and Y-SNP/STR (MY), by multiplex PCR and 150-bp paired-end sequencing, including 114 Y-SNPs (twelve dominant Y-DNA haplogroups), 45 Y-STRs (N-1 stutter < 0.09; estimated mutation rate < 5 × 10-3), and 22 MHs (allele coverage ratio > 0.91; pairwise distance > 10 Mb). Additionally, MY system-based genotype pattern recognition (GPR), a regression-based method to identify the genotype pattern for each MH locus, is proposed for two-person DNA mixture deconvolution. We integrated 26 two-person genotype combinations into nine genotype patterns and validated the application range of GPR based on DNA profiles of ten sets of simulated male-male DNA mixtures (1:10-1:2). RESULTS: The effective number of alleles (Ae) ranged from 3.62 to 14.72, with an average of 7.17, in 100 Chinese Guangdong Han individuals. The cumulative discrimination power was 1-5.00 × 10-31, and the cumulative power of exclusion was 1-5.00 × 10-8 and 1-4.85 × 10-12 for duo and trio paternity testing, respectively. Furthermore, the actual mixing ratio-depth of coverage (DoC) ratio (RDoC) regression relationships were established for different genetic markers and genotype patterns. In five overlapping areas, genotype differentiation of the major and minor contributors required likelihood ratio methods. In nonoverlapping areas, the genotype pattern could be recognized by comparing the observed RDoC and RDoC ranges. CONCLUSION: The GPR can be used to deconvolute two-person DNA mixtures (application range: 1:10-1:2) for individual identification.

3.
Mol Biol Rep ; 2022 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-35366759

RESUMO

BACKGROUND: Extracellular vesicles (EVs) contain thousands of proteins and nucleic acids, playing an important role in cell-cell communications. Sertoli cells have been essential in the testis as a "nurse cell". However, EVs derived from human Sertoli cells (HSerCs) have not been well investigated. METHODS: EVs were isolated from HSerCs via ultracentrifugation and characterized by transmission electron microscopy, tunable resistive pulse sensing, and Western blotting. The cargo carried by HSerCs-EVs was measured via liquid chromatography-mass spectrometry and GeneChip miRNA Arrays. Bioinformatic analysis was performed to reveal potential functions of HSerCs-EVs. RESULTS: A total of 860 proteins with no less than 2 unique peptides and 88 microRNAs with high signal values were identified in HSerCs-EVs. Biological processes related to molecular binding, enzyme activity, and regulation of cell cycle were significantly enriched. Specifically, many proteins in HSerCs-EVs were associated with spermatogenesis and regulation of immune system, including Septins, Large proline-rich protein BAG6, Clusterin, and Galectin-1. Moreover, abundant microRNAs within HSerCs-EVs (miR-638, miR-149-3p, miR-1246, etc.) had a possible impact on male reproductive disorders such as asthenozoospermia and oligozoospermia. CONCLUSIONS: Our study has shown that HSerCs-EVs contain diverse components such as proteins and microRNAs. Further research is required to evaluate HSerCs-EVs in spermatogenesis, which are underutilized but highly potent resources with particular promise for male infertility.

4.
Front Endocrinol (Lausanne) ; 13: 844360, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35355567

RESUMO

Apelin (APLN), as a ligand for APJ (an orphan G-protein-coupled receptor), is an adipokine with pleiotropic effects in many physiological processes of the body. It has an important role in the control of reproduction particularly in females (mainly in control of ovarian function). This study was carried out to investigate the mRNA and protein amounts of APLN/APJ in granulose cells (GCs) of ovarian follicles with small (SF), medium (MF), and large (LF) sizes of buffalo (Bubalus bubalis) and the effect of IGF1 and follicle-stimulating hormone (FSH) on the expression levels of APLN/APJ. In addition, we evaluated the effect of various doses of APLN (isoforms -13 and -17) singly or in combination with IGF1 and FSH on estradiol (E2) and progesterone (P4) secretion in GCs. The mRNA and protein abundance of APLN was the highest in GCs of LF while the APJ expression enhanced with follicle enlargement in GCs (p-value <0.01). IGF1 and FSH elevated the mRNA and protein amounts of APLN and FSH, and IGF1 increased the expression of APJ in buffalo GCs (p-value <0.01). Both isoforms of APLN (-13/-17) singly or in the presence of IGF1 or FSH increased the secretion of E2 and P4 with or without preincubation of cells with APJ antagonist (ML221 10 µM), although we had some variation in the effects. Concurrently, APLN-13/-17 significantly increased the mRNA and protein expression of CYP19A1 and StAR (p-value <0.01). ML221 substantially diminished the secretion of E2 and P4 and also the expression of CY19A1 and StAR in buffalo GCs (p-value <0.01). We also revealed that APLN-13/-17 (10-9 M), singly or in response to IGF1 and FSH, increased the production of E2 and P4 in different times of stimulation. In conclusion, APLN may play a crucial role in steroidogenesis and follicular development in ovarian GCs of buffalo.


Assuntos
Búfalos , Ovário , Animais , Apelina/genética , Apelina/metabolismo , Apelina/farmacologia , Receptores de Apelina/metabolismo , Feminino , Células da Granulosa
5.
Mol Med Rep ; 25(2)2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34878152

RESUMO

Mitochondrial trifunctional protein (MTP) deficiency (MTPD; MIM 609015) is a metabolic disease of fatty acid oxidation. MTPD is an autosomal recessive disorder caused by mutations in the HADHA gene, encoding the α­subunit of a trifunctional protease, or in the HADHB gene, encoding the ß­subunit of a trifunctional protease. To the best of our knowledge, only two cases of families with MTPD due to HADHB gene mutations have been reported in China, and the HADHA gene mutation has not been reported in a Chinese family with MTPD. The present study reported the clinical characteristics and compound heterozygous HADHA gene mutations of two patients with MTPD in the Chinese population. The medical history, routine examination data, blood acyl­carnitine analysis results, results of pathological examination after autopsy and family pedigree map were collected for patients with MTPD. The HADHA gene was analyzed by Sanger sequencing or high­throughput sequencing, the pathogenicity of the newly discovered variant was interpreted by bioinformatics analysis, and the function of the mutated protein was modeled and analyzed according to 3D structure. The two patients with MTPD experienced metabolic crises and died following an infectious disease. Lactate dehydrogenase, creatine kinase (CK), CK­MB and liver enzyme abnormalities were observed in routine examinations. Tandem mass spectrometry revealed that long­chain acyl­carnitine was markedly elevated in blood samples from the patients with MTPD. The autopsy results for one child revealed fat accumulation in the liver and heart. Next­generation sequencing detected compound heterozygous c.703C>T (p.R235W) and c.2107G>A (p.G703R) mutations in the HADHA gene. The mother did not have acute fatty liver during pregnancy with the two patients. Using amniotic fluid prenatal diagnostic testing, the unborn child was confirmed to carry only c.2107G>A (p.G703R). Molecular mechanistic analysis indicated that the two variants affected the conformation of the α­subunit of the MTP enzyme complex, and consequently affected the stability and function of the enzyme complex. The present study comprehensively analyzed the cases, including exome sequencing and protein structure analysis and, to the best of our knowledge, describes the first observation of compound heterozygous mutations in the HADHA gene underlying this disorder in China. The clinical phenotypes of the two heterozygous variants of the HADHA gene are non­lethal. The present study may improve understanding of the HADHA gene mutation spectrum and clinical phenotype in the Chinese population.


Assuntos
Cardiomiopatias/genética , Erros Inatos do Metabolismo Lipídico/genética , Miopatias Mitocondriais/genética , Subunidade alfa da Proteína Mitocondrial Trifuncional/genética , Proteína Mitocondrial Trifuncional/deficiência , Complexos Multienzimáticos/genética , Doenças do Sistema Nervoso/genética , Rabdomiólise/genética , /genética , Pré-Escolar , Feminino , Predisposição Genética para Doença , Testes Genéticos/métodos , Heterozigoto , Humanos , Lactente , Masculino , Proteína Mitocondrial Trifuncional/genética , Subunidade alfa da Proteína Mitocondrial Trifuncional/química , Modelos Moleculares , Mutação , Linhagem , Fenótipo , Conformação Proteica
6.
Carbohydr Polym ; 276: 118715, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34823761

RESUMO

Four fractions of water-extracted Sepia esculenta ink polysaccharides (SIP) were separated by dicthylaminoethy (DEAE) cellulose chromatography. The eluted fraction with the highest yield was characterized as a sulfate-rich glycosaminoglycan named SIP-IV. According to the analysis of laser scattering and refractive index signals, SIP-IV was determined to be 14.4 kDa and spherical molecular conformation in salt solution. SIP-IV is composed of fucose, galactosamine, glucosamine, mannose and glucuronic acid with a molar ratio of 5.1:7.3:3.8:1:4.4, which is obviously different from reported SIPs. SIP-IV promoted yeast proliferation and intercellular antioxidant level. Based on multi-omics strategy, data of transcriptome analysis suggested that growth promotion of SIP-IV on Saccharomyces cerevisiae might be attributed to regulation of Rho protein signal transduction, nuclear autophagy and nitrogen utilization. Combined with the metabolome results, SIP-IV also re-profiled metabolism of amino acids and phospholipids in yeast cells.


Assuntos
Glicosaminoglicanos/farmacologia , Saccharomyces cerevisiae/efeitos dos fármacos , Sepia/química , Sulfatos/química , Animais , Antioxidantes/metabolismo , Autofagia/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Glicosaminoglicanos/química , Tinta , Metaboloma , Conformação Molecular , Peso Molecular , Saccharomyces cerevisiae/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transcriptoma
7.
Int J Qual Health Care ; 34(1)2022 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-34962273

RESUMO

BACKGROUND: Radiological examinations and laboratory tests are routinely ordered by hospital physicians as part of the care plan to diagnose and treat patients. However, the failure to actively review and follow-up on these results pose a significant problem to patient safety. A study team was formed to mitigate the clinical risks of poor results management, which was identified as a top clinical risk in our organization, in order to make improvements to the results management process and to ensure the timely review, acknowledgement and follow-up of test results. OBJECTIVE: This study was carried out to improve results management processes and ensure the timely review, acknowledgment, and follow-up of test results, in order to mitigate the clinical risks posed to patient safety. METHODS: The institutional expectations of results management were set and published as a hospital policy, which was communicated to all clinical departments for compliance. Improvements to the electronic medical records system were made to facilitate the results acknowledgement process, and physicians were engaged to educate them on the importance of results management. RESULTS: The study team observed a decrease in unacknowledged results from approximately 16 000 in March 2017 to 2673 in December 2020. The compliance rate for acknowledgement results increased from a monthly average of 83.7% (from March to December 2017) to a monthly average of 99.3% (in 2020). The risk score for results management decreased from 16 to 6.5 and was excluded from the organization's top clinical risks. CONCLUSION: This study showed the importance of both system improvements and culture changes that are required to improve the process of results management and provides a step forward for the hospital to safeguard patient safety and mitigate clinical risk.


Assuntos
Hospitais , Segurança do Paciente , Humanos
8.
Asian J Androl ; 2021 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-34916478

RESUMO

Testicular endothelial cells have been found to play an important role in spermatogenesis and fertility, but their mechanism is obscure. Exosomes released by various cells are recognized as cell-cell communication mediators during the initiation and progression of many diseases. Therefore, the current study aimed to investigate the protein and miRNA components of human testicular endothelial cell-derived exosomes (HTEC-Exos) and to explore their potential effects on spermatogenesis. In this study, HTEC-Exos were first isolated by the ultracentrifugation method, and then identified by nanoparticle tracking analysis, transmission electron microscopy (TEM), and western blotting. The characteristics of HTEC-Exos were examined by liquid chromatography-mass spectrometry and microRNA (miRNA) chip analysis. Bioinformatics analysis was performed to explore the potential role of the exosomal content on spermatogenesis. A total of 945 proteins were identified, 11 of which were closely related to spermatogenesis. A total of 2578 miRNAs were identified. Among them, 30 miRNAs demonstrated potential associations with male reproductive disorders, such as azoospermia, and spermatogenesis disorders. In particular, 11 out of these 30 miRNAs have been proven to be involved in spermatogenesis based on available evidence. This study provides a global view of the proteins and miRNAs from HTEC-Exos, suggesting that HTEC-Exos may function as potential effectors during the process of spermatogenesis.

9.
Front Nutr ; 8: 769223, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34778348

RESUMO

Bovine milk-derived extracellular vesicles (BM-EVs) are recognized as promising nanoscale delivery vectors owing to their large availability. However, few isolation methods can achieve high purity and yield simultaneously. Therefore, we developed a novel and cost-effective procedure to separate BM-EVs via "salting-out." First, BM-EVs were isolated from skimmed milk using ammonium sulfate. The majority of BM-EVs were precipitated between 30 and 40% saturation and 34% had a relatively augmented purity. The separated BM-EVs showed a spherical shape with a diameter of 60-150 nm and expressed the marker proteins CD63, TSG101, and Hsp70. The purity and yield were comparable to the BM-EVs isolated via ultracentrifugation while ExoQuick failed to separate a relatively pure fraction of BM-EVs. The uptake of BM-EVs into endothelial cells was dose- and time-dependent without significant cytotoxicity. The levels of endothelial nitric oxide syntheses were regulated by BM-EVs loaded with icariside II and miRNA-155-5p, suggesting their functions as delivery vehicles. These findings have demonstrated that it is an efficient procedure to isolate BM-EVs via "salting-out," holding great promise toward therapeutic applications.

10.
J Cancer ; 12(23): 7138-7146, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34729115

RESUMO

Esophageal cancer (EC) is a lethal cancer with an extremely aggressive nature and poor survival rate. However, the molecular mechanisms driving the occurrence and progression of EC are not well understood. MicroRNAs (miRNAs) are small RNA molecules that regulate the expression of protein-coding genes. miRNA-mediated gene regulation plays an important role in EC. By cross-referencing studies from NCBI, we found that microRNA-375 (miR-375) is one of the most frequently downregulated miRNAs in EC. We assessed expression of miR-375 in EC cell lines and primary EC tissues and their matched normal tissues. We found significant downregulation of miR-375 in both cell lines and EC tissues. Forced expression of miR-375 attenuated EC cell proliferation and invasion. Human epidermal growth factor receptor 2 (HER2, ERBB2), a known proto-oncogene, was identified here as one of the potential target genes of miR-375. Ectopic expression of miR-375 significantly suppressed the expression of ERBB2 and subsequently downregulated one of its target genes, vascular endothelial growth factor A (VEGFA), which is related to cancer invasion and metastasis. These findings suggest that miR-375 acts as a tumor suppressor by blocking the ERBB2/VEGFA pathway with the potential to modulate the occurrence and/ or progression of EC.

11.
Cells ; 10(9)2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34571940

RESUMO

Lichen sclerosus (LS) is a chronic inflammatory skin disorder with unknown pathogenesis. The aberrant expression of microRNAs (miRNAs) is considered to exert a crucial role in LS. We used the next-generation sequencing technology (RNASeq) for miRNA profiling and Ingenuity Pathway Analysis (IPA) for molecular network analysis. We performed qRT-PCR, miRNA transfection and Matrigel assays for functional studies. We identified a total of 170 differentially expressed miRNAs between female LS and matched adjacent normal tissue using RNASeq, with 119 upregulated and 51 downregulated. Bioinformatics analysis revealed molecular networks that may shed light on the pathogenesis of LS. We verified the expression of a set of miRNAs that are related to autoimmunity, such as upregulated miR-326, miR-142-5p, miR-155 and downregulated miR-664a-3p and miR-181a-3p in LS tissue compared to the matched adjacent normal tissue. The differentially expressed miRNAs were also verified in blood samples from LS patients compared to healthy female volunteers. Functional studies demonstrated that a forced expression of miR-142-5p in human dermal fibroblast PCS-201-010 cells resulted in decreased cell proliferation and migration. These findings suggest that differentially expressed miRNAs may play an important role in LS pathogenesis; therefore, they could serve as biomarkers for LS management.


Assuntos
Biomarcadores/análise , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Líquen Escleroso e Atrófico/patologia , MicroRNAs/genética , Pele/metabolismo , Biologia Computacional , Feminino , Fibroblastos/metabolismo , Perfilação da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Líquen Escleroso e Atrófico/genética
12.
Research (Wash D C) ; 2021: 9759601, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34368767

RESUMO

The facial expressions are a mirror of the elusive emotion hidden in the mind, and thus, capturing expressions is a crucial way of merging the inward world and virtual world. However, typical facial expression recognition (FER) systems are restricted by environments where faces must be clearly seen for computer vision, or rigid devices that are not suitable for the time-dynamic, curvilinear faces. Here, we present a robust, highly wearable FER system that is based on deep-learning-assisted, soft epidermal electronics. The epidermal electronics that can fully conform on faces enable high-fidelity biosignal acquisition without hindering spontaneous facial expressions, releasing the constraint of movement, space, and light. The deep learning method can significantly enhance the recognition accuracy of facial expression types and intensities based on a small sample. The proposed wearable FER system is superior for wide applicability and high accuracy. The FER system is suitable for the individual and shows essential robustness to different light, occlusion, and various face poses. It is totally different from but complementary to the computer vision technology that is merely suitable for simultaneous FER of multiple individuals in a specific place. This wearable FER system is successfully applied to human-avatar emotion interaction and verbal communication disambiguation in a real-life environment, enabling promising human-computer interaction applications.

13.
Am J Cancer Res ; 11(7): 3594-3610, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34354862

RESUMO

Esophageal cancer (EC) is extremely aggressive and has a very poor survival rate. Esophageal squamous cell carcinoma (ESCC) accounts for 80% of all ECs worldwide, with the majority of the remaining 20% being esophageal adenocarcinoma (EAC). Due to its occult and insidious presentation, ESCC is typically diagnosed and treated in its advanced stages, thereby limiting the success of present therapeutic modalities. microRNAs (miRNAs) can function as tumor suppressors or oncogenes, playing critical roles in cancer initiation and progression by regulating target genes in oncogenic pathways. In the current study, we demonstrated that microRNA-196b (miR-196b) is one of the most upregulated miRNAs in both ESCC and EAC. miR-196b was overexpressed in ESCC and EAC cell lines, cellular exosomal RNAs, and ESCC tissue samples. Functional studies revealed that miR-196b acted as an oncomiR by directly targeting a tumor suppressor, ephrin type-A receptor 7 (EPHA7). EPHA7 abrogates the activity of ephrin type-A receptor 2 (EPHA2), a key molecule involved in the epithelial-to-mesenchymal transition (EMT) and MAPK/ERK pathways, mediating resistance to UV and chemoradiotherapy in both ESCC and EAC. Taken together, these findings suggest that miR-196b is a strong candidate molecular target for EC treatment.

14.
Forensic Sci Int ; 325: 110892, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34273604

RESUMO

BACKGROUND: The concentration levels of major and trace elements are significantly correlated with human health. However, studies profiling major and trace elements among female using methamphetamine are rare. This study aims to investigate the major and trace elements changes and discover elemental biomarkers in plasma of female methamphetamine (METH) addicts in six months' compulsory treatment. METHODS: A total of 60 female METH addicts selected from drug rehabilitation center were randomly divided into three equal groups: (1) Detoxification for one month; (2) Detoxification for three months; (3) Detoxification for six months. Twenty healthy women, without drug abuse history were selected as control group. Four major elements including Na, Mg, K, Ca and twelve trace elements including V, Cr, Mn, Fe, Ni, Cu, Zn, As, Se, Mo, Sn, Pb were determined using inductively coupled plasma mass spectrometry (ICP-MS). The results were analyzed using One-way Analysis of Variance (ANOVA) and Student-Newman-Keuls (SNK test). Elemental biomarkers were discovered based on orthogonal partial least squares discriminant analysis (OPLS-DA). RESULTS: The four groups used in the study were divided into four significant sections according to scatter plots. The total elemental concentrations of three METH withdrawal groups were increased compared to the control group. Over six months, element contents of the withdrawal groups gradually equaled element contents of the control group in compulsory treatment. The variable importance in the projection values (VIP > 1) of OPLS-DA model and SNK test (p < 0.05) revealed Fe, Cu, Cr and Se as elemental biomarkers. CONCLUSION: Major and trace elements demonstrated significant differences between control group and three METH withdrawal groups. Fe, Cu, Cr and Se are potential elemental biomarkers among METH-abused female groups. Metabolic disorders of major and trace elements exist in the female methamphetamine addicts.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas/reabilitação , Oligoelementos/sangue , Adulto , Biomarcadores/sangue , Feminino , Humanos , Espectrometria de Massas/métodos , Metanfetamina/efeitos adversos , Centros de Tratamento de Abuso de Substâncias
15.
Toxicol Lett ; 350: 98-110, 2021 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-34214594

RESUMO

Methamphetamine (METH) is a highly addictive amphetamine-type drug that has caused persistent harm to society and human health in recent years. Most studies have shown that METH severely damages the central nervous system, and this drug has been found to be toxic to the cardiovascular system in recent years. Therefore, we hypothesized that METH may also damage vascular smooth muscle. We examined the expression of the apoptosis-related proteins Caspase 3 and PARP after METH treatment in vivo and in vitro and detected the expression of endoplasmic reticulum stress-related proteins. After treatment with the endoplasmic reticulum stress inhibitor 4-PBA, changes in the above indicators were examined. C/EBP homologous protein (Chop) expression was also detected, and the relationship between endoplasmic reticulum stress and apoptosis was further determined by siRNA silencing of Chop. The results indicated that METH can induce apoptosis of vascular smooth muscle cells (VSMCs) and upregulate the expression of Chop and endoplasmic reticulum stress-related proteins. Chop inhibits protein kinase B phosphorylation and further inhibits forkhead box class O3a (Foxo3a) dephosphorylation, resulting in increased p53 upregulated molecular of apoptosis (PUMA) transcription. Increased PUMA induces apoptosis through the mitochondrial pathway. These results indicate that Chop is involved in the METH-induced endoplasmic reticulum stress and apoptosis in VSMCs and may be a potential therapeutic target for METH-induced VSMC injury.


Assuntos
Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Metanfetamina/toxicidade , Músculo Liso Vascular/efeitos dos fármacos , Animais , Humanos , Masculino , Modelos Animais , Ratos Sprague-Dawley , Fator de Transcrição CHOP/metabolismo
16.
J Food Biochem ; 45(5): e13717, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33844306

RESUMO

In order to further explore the potential pharmacological activity of astaxanthin (AST), network pharmacological approaches were employed in this work to systematically investigate its affinity targets, perturbed signaling pathways, and related disease applications. First, potential targets were captured based on AST chemical structure information. Enrichment analysis was then performed using bioinformatics tools to predict the biological processes and diseases in which AST targets are involved. The results suggest that AST is involved in steroid hormone metabolism, and the regulation of glucocorticoids may be one of the potential mechanisms of its known therapeutic effects on depression and insulin resistance. Molecular docking experiments confirmed that AST can form stable binding to several key nodes (SRD5A2, STS, AKR1C2, HSD11B1, and CYP17A1) in steroid hormone biosynthesis. More importantly, the molecular targets of AST were the most significantly associated with endometriosis. Functionally, grouped analysis of key therapeutic nodes was carried out by establishing the interaction network between drug targets and disease targets. While exerting inflammatory effects, the regulation of estrogen and other semiochemicals by targeting steroid metabolism may be the biological basis for the potential treatment of endometriosis with AST. This work provides a theoretical basis for further exploring the pharmacological mechanisms of AST and development of new therapeutic applications. PRACTICAL APPLICATIONS: In this study, systematic pharmacological methods were used to identify the potential therapeutic effects and associated mechanisms of astaxanthin, providing a bioinformatics basis for further exploration of astaxanthin's new pharmacological properties in foods.


Assuntos
Medicamentos de Ervas Chinesas , Feminino , Humanos , Simulação de Acoplamento Molecular , Mapas de Interação de Proteínas , Transdução de Sinais , Xantofilas
17.
Mar Drugs ; 19(5)2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33922488

RESUMO

This work aimed to investigate the effect of fucoidan (FPS) on urate transporters induced by uric acid (UA). The results showed that UA stimulated the expression of glucose transporter 9 (GLUT9) and urate transporter 1 (URAT1) in HK-2 cells, and FPS could reverse the effect. Moreover, UA could activate NF-κB, JNK and PI3K/Akt pathways, but both pathway inhibitors and FPS inhibited the UA-induced activation of these three pathways. These data suggested that FPS effectively inhibited the expression induction of reabsorption transporters URAT1 and GLUT9 by UA, through repressing the activation of NF-κB, JNK and PI3K/Akt signal pathways in HK-2 cells. The in vitro research findings support the in vivo results that FPS reduces serum uric acid content in hyperuricemia mice and rats through inhibiting the expression of URAT1 and GLUT9 in renal tubular epithelial cells. This study provides a theoretical basis for the application of FPS in the treatment of hyperuricemia.


Assuntos
Proteínas Facilitadoras de Transporte de Glucose/metabolismo , Supressores da Gota/farmacologia , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Túbulos Renais Proximais/efeitos dos fármacos , Laminaria , NF-kappa B/metabolismo , Transportadores de Ânions Orgânicos/metabolismo , Proteínas de Transporte de Cátions Orgânicos/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Polissacarídeos/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Linhagem Celular , Supressores da Gota/isolamento & purificação , Humanos , Túbulos Renais Proximais/enzimologia , Laminaria/química , Polissacarídeos/isolamento & purificação , Transdução de Sinais , Ácido Úrico/toxicidade
18.
Forensic Sci Int ; 321: 110745, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33676237

RESUMO

We present a case of fatal poisoning from accidental ingestion of Gelsemium elegans (G. elegans), a rarely toxic plant. A 41-year-old man was found dead, at his home, 6 h after drinking homemade herbal liqueur during lunch. Autopsy and routine toxicological analyses identified neither significant pathological findings nor routine poisons. However, a local botanist revealed that the homemade herbal liqueur contained G. elegans, a poisonous plant specific to Asia. To ascertain whether the decedent had ingested G. elegans, we performed liquid chromatography-mass spectrometry (LC-MS) and found two alkaloids (gelsemine and koumine) in his blood, gastric contents, as well as the suspected herbal liqueur. The cause of death was therefore confirmed to be G. elegans poisoning. Case reports of fatal poisoning due to ingestion of G. elegans are quite rare in English. Therefore, the present case broadens the scope on the possibility of death due to ingestion of G. elegans for forensic pathologists and toxicologists.


Assuntos
Acidentes , Gelsemium/envenenamento , Adulto , Alcaloides/análise , Bebidas , Cromatografia Líquida , Evolução Fatal , Conteúdo Gastrointestinal/química , Humanos , Alcaloides Indólicos/análise , Masculino , Espectrometria de Massas , Plantas Tóxicas
19.
Forensic Sci Med Pathol ; 17(1): 114-119, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33170459

RESUMO

We describe a case of a 32-year-old man who died due to bilateral re-expansion pulmonary edema (RPE) following the insertion a chest tube for unilateral spontaneous pneumothorax. Fifteen minutes after inserting the chest tube, the patient with right spontaneous pneumothorax was diagnosed with right re-expansion edema by chest radiograph. Although multiple treatments were administered, the patient died. However, the findings from autopsy showed bilateral RPE existed in the decedent but not unilateral RPE. Autopsy, microscopic examination, and clinical records concluded that the cause of death was acute cardiac and respiratory failure due to bilateral re-expansion pulmonary edema following unilateral spontaneous pneumothorax. Bilateral RPE due to a unilateral pneumothorax is quite rare in clinical and forensic practice. To the best of our knowledge, this is the first time that the pathological changes of RPE have been described by gross and microscopic examinations. This case is reported to provide histopathologic references for diagnosis of RPE and indicate that combining death investigation, pathological findings and clinical courses plays a vital role in diagnosis of RPE in forensic pathology.


Assuntos
Tubos Torácicos/efeitos adversos , Pneumotórax/terapia , Edema Pulmonar/etiologia , Adulto , Evolução Fatal , Insuficiência Cardíaca/etiologia , Humanos , Masculino , Insuficiência Respiratória/etiologia
20.
RSC Adv ; 11(6): 3596-3602, 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-35424304

RESUMO

To explore the interactive molecules of squid ink polysaccharides (SIP) for further understanding the action mechanisms of SIP bio-function, this study prepared SIP binding proteins from mouse liver using superparamagnetic nanometer beads. Michaelis-Menten constant (K m) was detected from a Lineweaver-Burk double reciprocal plot to assess effect of SIP on activity of aldehyde oxidase (AOX). Results showed that three proteins, AOX-3, regucalcin (RGN) and α1-antitrypsin (A1AT3) were separated from mouse liver by magnetic nanoparticles conjugated with SIP. Contents of AOX-3 were much more than RGN and A1AT3. SIP (0.5 mg mL-1) reduced K m value of aldehyde oxidase of mouse liver from 91.79 µmol L-1 to 43.70 µmol L-1.

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