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1.
Anal Chem ; 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38833511

ABSTRACT

A compact spectrometer based on a mid-infrared optical sensor has been developed for high-precision and real-time measurement of water isotope ratios. The instrument uses laser absorption spectroscopy and applies the weighted Kalman filtering method to determine water isotope ratios with high precision and fast time response. The precision of the measurements is 0.41‰ for δ18O and 0.29‰ for δ17O with a 1 s time. This is much faster than the standard running average technique, which takes over 90 s to achieve the same level of precision. The successful development of this compact mid-infrared optical sensor opens up new possibilities for its future applications in atmospheric and breath gas research.

2.
iScience ; 27(5): 109713, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38746668

ABSTRACT

This study systematically reviewed the application of large language models (LLMs) in medicine, analyzing 550 selected studies from a vast literature search. LLMs like ChatGPT transformed healthcare by enhancing diagnostics, medical writing, education, and project management. They assisted in drafting medical documents, creating training simulations, and streamlining research processes. Despite their growing utility in assisted diagnosis and improving doctor-patient communication, challenges persisted, including limitations in contextual understanding and the risk of over-reliance. The surge in LLM-related research indicated a focus on medical writing, diagnostics, and patient communication, but highlighted the need for careful integration, considering validation, ethical concerns, and the balance with traditional medical practice. Future research directions suggested a focus on multimodal LLMs, deeper algorithmic understanding, and ensuring responsible, effective use in healthcare.

3.
Animals (Basel) ; 14(3)2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38338134

ABSTRACT

Figla is one of the earliest expressed genes in the oocyte during ovarian development. In this study, Figla was characterized in C. maculata, one of the main aquaculture species in China, and designated as CmFigla. The length of CmFigla cDNA was 1303 bp, encoding 197 amino acids that contained a conserved bHLH domain. CmFigla revealed a female-biased expression patterns in the gonads of adult fish, and CmFigla expression was far higher in ovaries than that in testes at all gonadal development stages, especially at 60~180 days post-fertilization (dpf). Furthermore, a noteworthy inverse relationship was observed between CmFigla expression and the methylation of its promoter in the adult gonads. Gonads at 90 dpf were used for in situ hybridization (ISH), and CmFigla transcripts were mainly concentrated in oogonia and the primary oocytes in ovaries, but undetectable in the testes. These results indicated that Figla would play vital roles in the ovarian development in C. maculata. Additionally, the frame-shift mutations of CmFigla were successfully constructed through the CRISPR/Cas9 system, which established a positive foundation for further investigation on the role of Figla in the ovarian development of C. maculata. Our study provides valuable clues for exploring the regulatory mechanism of Figla in the fish ovarian development and maintenance, which would be useful for the sex control and reproduction of fish in aquaculture.

4.
BMC Genom Data ; 24(1): 45, 2023 08 12.
Article in English | MEDLINE | ID: mdl-37573319

ABSTRACT

BACKGROUND: Distant hybridization is an important breeding technique for creating new strains with superior traits by integrating two different genomes. Successful hybridization of Megalobrama amblycephala (Blunt snout bream, BSB, 2n = 48) and Culter alburnus (Topmouth culter, TC, 2n = 48) was achieved to establish hybrid lineages (BT and TB), which provide valuable materials for exploring the mechanisms of distant hybridization fertility. In this study, the gonadal tissue transcriptomes of BSB, TC, BT-F1, and TB-F1 were sequenced using Illumina high-throughput sequencing technology to analyze the reproductive characteristics of BT and TB. RESULTS: Differential gene expression analysis showed that the differentially expressed genes in BT vs BSB and BT vs TC were mainly enriched in signaling pathways not directly associated with meiosis. While, the differentially expressed genes of TB vs BSB and TB vs TC were mainly enriched in pathways related to meiosis, and most of them were down-regulated, indicating that meiosis is suppressed in TB. Under-dominance (UD) genes were enriched in pathways related to meiosis and DNA repair in TB. Over-dominance (OD) genes were enriched in MAPK signaling pathway, expression level dominance-BSB (ELD-B) genes were enriched in pathways related to steroid hormone synthesis and expression level dominance-TC (ELD-T) genes were not significantly enriched in any pathway in both BT and TB. CONCLUSIONS: These results suggest that meiotic progression may not be affected in BT, whereas it is clearly inhibited in TB. Offspring of M. amblycephala maternal parent may have better genomic compatibility and fertility. Our study provides important information on the molecular mechanisms of breaking reproductive isolation in distantly hybridized fertile lineages.


Subject(s)
Cyprinidae , Cypriniformes , Animals , Transcriptome/genetics , Hybridization, Genetic , Cyprinidae/genetics , Cypriniformes/genetics , Gene Expression Profiling
5.
Spectrochim Acta A Mol Biomol Spectrosc ; 302: 123044, 2023 Dec 05.
Article in English | MEDLINE | ID: mdl-37354856

ABSTRACT

The measurement of the line positions and effective line strengths of the ν3 fundamental band of trans-nitrous acid (trans-HONO) near 1280 cm-1 (7.8 µm) by tunable laser absorption spectroscopy (TLAS) utilizing a room temperature continuous-wave quantum cascade laser (cw-QCL) was reported. The effective line strengths of 30 well-resolved trans-HONO absorption lines in the range of 1279.8-1282.2 cm-1 were determined using the HONO line strength at 1280.3841 cm-1 as a scale. The maximum measurement uncertainty of 7.64% in the line strengths is mainly determined by the uncertainty of the referenced line strength, while the measurement precision of the line positions is better than 5.56 * 10-3 cm-1. The line positions and strengths of the trans-HONO absorption lines obtained in this work provide a reference for continuous gas monitoring and analysis of the sources and sinks of atmospheric HONO.

6.
Spectrochim Acta A Mol Biomol Spectrosc ; 283: 121762, 2022 Dec 15.
Article in English | MEDLINE | ID: mdl-35985233

ABSTRACT

Simultaneous measurement of H217O/H216O, H218O/H216O, and HDO/H216O in air with a compact spectrometer based on a mid-infrared distributed feedback (DFB) laser was described. The obtained mixing ratios of H216O, H217O, and H218O agreed reasonably well with those measured by a hygrometer. The precision and repeatability of the spectrometer were analyzed. Indoor air tests demonstrated that its 220-s precision was 0.08 ‰, 0.06 ‰, and 0.14 ‰ for δ18O, δ17O, and δ2H respectively. The measured values of δ18O, δ17O, and δ2H in indoor air were highly correlated with the water vapor mixing ratios. The compact spectrometer provides in situ measurements of water vapor isotopes with high precision and fast time response, which opens new possibilities for its application in atmospheric and hydrological research in the future.

7.
Front Psychiatry ; 13: 934428, 2022.
Article in English | MEDLINE | ID: mdl-35873223

ABSTRACT

Background: Although evidence-based and effective treatments are available for people with major depressive disorder (MDD), a substantial number do not seek or receive help. Therefore, this study aimed to (1) investigate the total help-seeking rate and first-time help-seeking choices; (2) explore the perceived helpfulness of 23 potential sources; and (3) evaluate the factors related to help-seeking behaviors among patients with MDD. Materials and Methods: Data came from the Tianjin Mental Health Survey (TJMHS), which included a representative sample of adult community residents (n = 11,748) in the Chinese municipality of Tianjin. Of these, 439 individuals were diagnosed with lifetime MDD according to the Diagnostic and Statistical Manual-fourth edition (DSM-IV) and administered a help-seeking questionnaire. Results: In a survey, 28.2% of patients with MDD living community reported that they had ever sought any help during their entire lifetime before the interview, with 8.2% seeking help in mental healthcare settings, 8.0% only in other healthcare settings, and 12.0% only in non-healthcare sources (e.g., family, friends, and spiritual advisor). Among help-seekers, the first help mainly was sought in non-healthcare sources (61.3%), followed by healthcare settings (25.8%) and mental healthcare settings (12.9%). The majority of MDD individuals thought the non-healthcare sources were not helpful and mental healthcare settings were helpful or possibly helpful to solve mental problems. Female, having 10-12 or higher education years, comorbid anxiety disorders were associated with increased help-seeking. Conclusion: A small percentage of individuals with MDD living in community of Tianjin sought help. They preferred non-healthcare sources to healthcare settings. Demographic and clinical features were associated with help-seeking behaviors.

8.
Comput Biol Med ; 147: 105799, 2022 08.
Article in English | MEDLINE | ID: mdl-35792472

ABSTRACT

PURPOSE: Deformable image registration (DIR) plays an important role in assisting disease diagnosis. The emergence of the Transformer enables the DIR framework to extract long-range dependencies, which relieves the limitations of intrinsic locality caused by convolution operation. However, suffering from the interference of missing or spurious connections, it is a challenging task for Transformer-based methods to capture the high-quality long-range dependencies. METHODS: In this paper, by staking the graph convolution Transformer (Graformer) layer at the bottom of the feature extraction network, we propose a Graformer-based DIR framework, named GraformerDIR. The Graformer layer is consist of the Graformer module and the Cheby-shev graph convolution module. Among them, the Graformer module is designed to capture high-quality long-range dependencies. Cheby-shev graph convolution module is employed to further enlarge the receptive field. RESULTS: The performance and generalizability of GraformerDIR have been evaluated on publicly available brain datasets including the OASIS, LPBA40, and MGH10 datasets. Compared with VoxelMorph, the GraformerDIR has obtained performance improvements of 4.6% in Dice similarity coefficient (DSC) and 0.055 mm in the average symmetric surface distance (ASD) while reducing the non-positive rate of Jacobin determinant (Npr.Jac) index about 60 times on publicly available OASIS dataset. On unseen dataset MGH10, the GraformerDIR has obtained the performance improvements of 4.1% in DSC and 0.084 mm in ASD compared with VoxelMorph, which demonstrates the GraformerDIR with better generalizability. The promising performance on the clinical cardiac dataset ACDC indicates the GraformerDIR is practicable. CONCLUSION: With the advantage of Transformer and graph convolution, the GraformerDIR has obtained comparable performance with the state-of-the-art method VoxelMorph.


Subject(s)
Image Processing, Computer-Assisted , Radiotherapy Planning, Computer-Assisted , Algorithms , Head , Image Processing, Computer-Assisted/methods , Radiotherapy Planning, Computer-Assisted/methods
9.
Pharm Biol ; 60(1): 1264-1277, 2022 Dec.
Article in English | MEDLINE | ID: mdl-35787093

ABSTRACT

CONTEXT: The litchi semen are traditional medications for treating liver fibrosis (LF) in China. The mechanism remains unclear. OBJECTIVE: This study investigates the anti-liver fibrotic mechanism of the total flavonoids of litchi semen (TFL). MATERIALS AND METHODS: Sprague-Dawley rats with carbon tetrachloride-induced LF were treated with TFL (50 and 100 mg/kg) for 4 weeks. The anti-liver fibrotic effects of TFL were evaluated and the underlying mechanisms were investigated via histopathological analysis, proteomic analysis and molecular biology technology. RESULTS: Significant anti-LF effects were observed in the high-TFL-dose group (TFL-H, p < 0.05). Five hundred and eighty-five and 95 differentially expressed proteins (DEPs) were identified in the LF rat model (M group) and TFL-H group, respectively. The DEPs were significantly enriched in the retinol metabolism pathway (p < 0.0001). The content of 9-cis-retinoic acid (0.93 ± 0.13 vs. 0.66 ± 0.10, p < 0.05, vs. the M group) increased significantly in the TFL-H group. The upregulation of RXRα (0.50 ± 0.05 vs. 0.27 ± 0.13 protein, p < 0.05), ALDH2 (1.24 ± 0.09 vs. 1.04 ± 0.08 protein, p < 0.05), MMP3 (0.89 ± 0.02 vs. 0.61 ± 0.12 protein, p < 0.05), Aldh1a7 (0.20 ± 0.03 vs. 0.03 ± 0.00 mRNA, p < 0.05) and Aox3 (0.72 ± 0.14 vs. 0.05 ± 0.01 mRNA, p < 0.05) after TFL treatment was verified. CONCLUSIONS: TFL exhibited good anti-liver fibrotic effects, which may be related to the upregulation of the retinol metabolism pathway. TFL may be promising anti-LF agents with potential clinical application prospects.


Subject(s)
Flavonoids , Litchi , Liver Cirrhosis , Animals , Flavonoids/pharmacology , Flavonoids/therapeutic use , Litchi/chemistry , Liver Cirrhosis/chemically induced , Liver Cirrhosis/drug therapy , Liver Cirrhosis/metabolism , Proteomics , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Seeds/chemistry , Up-Regulation , Vitamin A/adverse effects
10.
BMC Genom Data ; 23(1): 39, 2022 05 31.
Article in English | MEDLINE | ID: mdl-35641933

ABSTRACT

BACKGROUND: The influence of environmental factors, especially temperature, on sex ratio is of great significance to elucidate the mechanism of sex determination. However, the molecular mechanisms by which temperature affects sex determination remains unclear, although a few candidate genes have been found to play a role in the process. In this study, we conducted transcriptome analysis of the effects induced by high temperature on zebrafish during gonad differentiation period. RESULTS: Totals of 1171, 1022 and 2921 differentially expressed genes (DEGs) between high temperature and normal temperature were identified at 35, 45 and 60 days post-fertilization (dpf) respectively, revealing that heat shock proteins (HSPs) and DNA methyltransferases (DNMTs) were involved in the heat-exposed sex reversal. The Gene Ontology (GO) terms and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway that were enriched in individuals after heat treatment included Fanconi anemia (FA) pathway, cell cycle, oocyte meiosis and homologous recombination. CONCLUSIONS: Our study provides the results of comparative transcriptome analyses between high temperature and normal temperature, and reveals that the molecular mechanism of heat-induced masculinization in zebrafish is strongly related to the expression of HSPs and DNMTs and FA pathway during gonad differentiation.


Subject(s)
Fanconi Anemia , Zebrafish , Animals , Fanconi Anemia/metabolism , Gene Expression Profiling/methods , Gene Ontology , Gonads/metabolism , Transcriptome/genetics , Zebrafish/genetics
11.
Ann Hepatol ; 27(3): 100681, 2022.
Article in English | MEDLINE | ID: mdl-35124283

ABSTRACT

INTRODUCTION AND OBJECTIVE: Liver fibrosis (LF) often leads to cirrhosis and even hepatocellular carcinoma (HCC), but the molecular mechanism remains unclear. The aims of the present study were to identify potential biomarkers for the progression of LF to HCC and explore the associated molecular mechanisms. MATERIALS AND METHODS: The isobaric tags for relative and absolute quantitation (iTRAQ) was used to detect changes in the protein expression profiles of liver tissues and to screen the differentially expressed proteins (DEPs). The differentially expressed genes (DEGs) of LF rats and patients were screened by Gene Expression Database (GEO). Subsequently, the clinicopathological analysis of the overlapping genes in different pathological stages in HCC patients based on GEPIA database was conducted. RESULTS: iTRAQ proteomic analysis revealed 689, 749 and 585 DEPs in the 6W, 8W and 12W groups, respectively. ALDH2, SLC27A5 and ASNS were not only the DEPs found in rats with LF with different stages but were also the DEGs related to the pathological stages and survival in patients with HCC. CONCLUSIONS: ALDH2, SLC27A5 and ASNS were the potential biomarkers associated with the progression of LF to HCC.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Aldehyde Dehydrogenase, Mitochondrial , Animals , Biomarkers , Carcinoma, Hepatocellular/pathology , Humans , Liver Cirrhosis/genetics , Liver Neoplasms/pathology , Proteomics , Rats
12.
J Biol Chem ; 298(3): 101660, 2022 03.
Article in English | MEDLINE | ID: mdl-35124006

ABSTRACT

Diabetes normally causes lipid accumulation and oxidative stress in the kidneys, which plays a critical role in the onset of diabetic nephropathy; however, the mechanism by which dysregulated fatty acid metabolism increases lipid and reactive oxygen species (ROS) formation in the diabetic kidney is not clear. As succinate is remarkably increased in the diabetic kidney, and accumulation of succinate suppresses mitochondrial fatty acid oxidation and increases ROS formation, we hypothesized that succinate might play a role in inducing lipid and ROS accumulation in the diabetic kidney. Here we demonstrate a novel mechanism by which diabetes induces lipid and ROS accumulation in the kidney of diabetic animals. We show that enhanced oxidation of dicarboxylic acids by peroxisomes leads to lipid and ROS accumulation in the kidney of diabetic mice via the metabolite succinate. Furthermore, specific suppression of peroxisomal ß-oxidation improved diabetes-induced nephropathy by reducing succinate generation and attenuating lipid and ROS accumulation in the kidneys of the diabetic mice. We suggest that peroxisome-generated succinate acts as a pathological molecule inducing lipid and ROS accumulation in kidney, and that specifically targeting peroxisomal ß-oxidation might be an effective strategy in treating diabetic nephropathy and related metabolic disorders.


Subject(s)
Diabetes Mellitus, Experimental , Diabetic Nephropathies , Kidney , Peroxisomes , Succinic Acid , Animals , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Experimental/pathology , Diabetic Nephropathies/metabolism , Diabetic Nephropathies/pathology , Fatty Acids/metabolism , Female , Humans , Kidney/metabolism , Lipid Metabolism , Male , Mice , Oxidative Stress , Peroxisomes/metabolism , Reactive Oxygen Species/metabolism , Succinic Acid/metabolism
13.
J Biol Chem ; 298(2): 101572, 2022 02.
Article in English | MEDLINE | ID: mdl-35007532

ABSTRACT

Although diabetes normally causes an elevation of cholesterol biosynthesis and induces hypercholesterolemia in animals and human, the mechanism linking diabetes to the dysregulation of cholesterol biosynthesis in the liver is not fully understood. As liver peroxisomal ß-oxidation is induced in the diabetic state and peroxisomal oxidation of fatty acids generates free acetate, we hypothesized that peroxisomal ß-oxidation might play a role in liver cholesterol biosynthesis in diabetes. Here, we used erucic acid, a specific substrate for peroxisomal ß-oxidation, and 10,12-tricosadiynoic acid, a specific inhibitor for peroxisomal ß-oxidation, to specifically induce and suppress peroxisomal ß-oxidation. Our results suggested that induction of peroxisomal ß-oxidation increased liver cholesterol biosynthesis in streptozotocin-induced diabetic mice. We found that excessive oxidation of fatty acids by peroxisomes generated considerable free acetate in the liver, which was used as a precursor for cholesterol biosynthesis. In addition, we show that specific inhibition of peroxisomal ß-oxidation decreased cholesterol biosynthesis by reducing acetate formation in the liver in diabetic mice, demonstrating a crosstalk between peroxisomal ß-oxidation and cholesterol biosynthesis. Based on these results, we propose that induction of peroxisomal ß-oxidation serves as a mechanism for a fatty acid-induced upregulation in cholesterol biosynthesis and also plays a role in diabetes-induced hypercholesterolemia.


Subject(s)
Cholesterol , Diabetes Mellitus, Experimental , Hypercholesterolemia , Liver , Peroxisomes , Animals , Cholesterol/biosynthesis , Cholesterol/metabolism , Diabetes Mellitus, Experimental/metabolism , Fatty Acids/metabolism , Hypercholesterolemia/metabolism , Liver/metabolism , Mice , Microbodies/metabolism , Oxidation-Reduction , Peroxisomes/metabolism
14.
Med Phys ; 49(2): 952-965, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34951034

ABSTRACT

PURPOSE: Imaging registration has a significant contribution to guide and support physicians in the process of decision-making for diagnosis, prognosis, and treatment. However, existing registration methods based on the convolutional neural network cannot extract global features effectively, which significantly influences registration performance. Moreover, the smoothness of the displacement vector field (DVF) fails to be ensured due to the miss folding penalty. METHODS: In order to capture abundant global information as well as local information, we have proposed a novel 3D deformable image registration network based on Transformer (TransDIR). In the encoding phase, the transformer with the atrous reduction attention block is designed to capture the long-distance dependencies that are crucial for extracting global information. A zero-padding position encoder is embedded into the transformer to capture the local information. In the decoding phase, an up-sampling module based on an attention mechanism is designed to increase the significance of ROIs. Because of adding folding penalty term into loss function, the smoothness of DVF is improved. RESULTS: Finally, we carried out experiments on OASIS, LPBA40, MGH10, and MM-WHS open datasets to validate the effectiveness of TransDIR. Compared with LapIRN, the DSC score is improved by 1.1% and 0.9% on OASIS and LPBA40, separately. In addition, compared with VoxelMorph, the DSC score is improved by 2.8% on the basis of the folding index decreased by hundreds of times on MM-WHS. CONCLUSIONS: The results show that the TransDIR achieves robust registration and promising generalizability compared with LapIRN and VoxelMorph.


Subject(s)
Image Processing, Computer-Assisted , Neural Networks, Computer , Imaging, Three-Dimensional , Magnetic Resonance Imaging , Tomography, X-Ray Computed
15.
J Xray Sci Technol ; 29(6): 1065-1078, 2021.
Article in English | MEDLINE | ID: mdl-34719432

ABSTRACT

BACKGROUND: Convolutional neural network has achieved a profound effect on cardiac image segmentation. The diversity of medical imaging equipment brings the challenge of domain shift for cardiac image segmentation. OBJECTIVE: In order to solve the domain shift existed in multi-modality cardiac image segmentation, this study aims to investigate and test an unsupervised domain adaptation network RA-SIFA, which combines a parallel attention module (PAM) and residual attention unit (RAU). METHODS: First, the PAM is introduced in the generator of RA-SIFA to fuse global information, which can reduce the domain shift from the respect of image alignment. Second, the shared encoder adopts the RAU, which has residual block based on the spatial attention module to alleviate the problem that the convolution layer is insensitive to spatial position. Therefore, RAU enables to further reduce the domain shift from the respect of feature alignment. RA-SIFA model can realize the unsupervised domain adaption (UDA) through combining the image and feature alignment, and then solve the domain shift of cardiac image segmentation in a complementary manner. RESULTS: The model is evaluated using MM-WHS2017 datasets. Compared with SIFA, the Dice of our new RA-SIFA network is improved by 8.4%and 3.2%in CT and MR images, respectively, while, the average symmetric surface distance (ASD) is reduced by 3.4 and 0.8mm in CT and MR images, respectively. CONCLUSION: The study results demonstrate that our new RA-SIFA network can effectively improve the accuracy of whole-heart segmentation from CT and MR images.


Subject(s)
Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Attention , Heart/diagnostic imaging , Neural Networks, Computer
16.
Spectrochim Acta A Mol Biomol Spectrosc ; 263: 120187, 2021 Dec 15.
Article in English | MEDLINE | ID: mdl-34314970

ABSTRACT

An improved Savitzky-Golay (S-G) filtering algorithm was developed to denoise the absorption spectroscopy of nitrogen oxide (NO2). A deep learning (DL) network was introduced to the traditional S-G filtering algorithm to adjust the window size and polynomial order in real time. The self-adjusting and follow-up actions of DL network can effectively solve the blindness of selecting the input filter parameters in digital signal processing. The developed adaptive S-G filter algorithm is compared with the multi-signal averaging filtering (MAF) algorithm to demonstrate its performance. The optimized S-G filtering algorithm is used to detect NO2 in a mid-quantum-cascade-laser (QCL) based gas sensor system. A sensitivity enhancement factor of 5 is obtained, indicating that the newly developed algorithm can generate a high-quality gas absorption spectrum for applications such as atmospheric environmental monitoring and exhaled breath detection.


Subject(s)
Deep Learning , Algorithms , Exhalation , Signal Processing, Computer-Assisted , Spectrum Analysis
17.
ACS Omega ; 6(17): 11669-11678, 2021 May 04.
Article in English | MEDLINE | ID: mdl-34056322

ABSTRACT

Ovarian cancer is highly aggressive and has high rates of recurrence and metastasis. Due to the limited effects of current treatments, it is necessary to conduct research and develop new treatment options. The application of gene therapy in tumor therapy is gradually increasing and has exciting prospects. MicroRNA-7 (miR-7) has been reported to inhibit the growth, invasion, and metastasis of a variety of solid tumors. Cationic liposomes are safe and effective gene delivery systems for transfection in vivo and in vitro. To realize the application of miR-7 in the treatment of ovarian cancer, cationic liposomes were prepared with 1,2-dioleoyl-3-trimethylammonium-propane, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine, and cholesterol. The miR-7 liposomes had a suitable particle size, potential, and a high cellular uptake rate. MiR-7 encapsulated by liposomes could be effectively delivered to ovarian cancer cells and successfully targeted to the tumor site in a mouse xenograft model of ovarian cancer. In vitro and in vivo experiments revealed that the miR-7 liposomes had a significant ability to inhibit the growth, invasion, and migration of ovarian cancer, probably by inhibiting the expression of the epidermal growth factor receptor. Our studies of miR-7 liposomes demonstrated a safe and efficient microRNA delivery system for the gene therapy of ovarian cancer.

18.
J Biol Chem ; 296: 100622, 2021.
Article in English | MEDLINE | ID: mdl-33811861

ABSTRACT

Fasting induces lipid accumulation in the liver, while the mechanisms by which fasting dysregulates liver fatty acid oxidation are not clear. Fatty acid ω-oxidation is induced in the fasting state, and administration of dicarboxylic acids to fasting animals decreases plasma ketone bodies. We hypothesized that endogenous dicarboxylic acids might play a role in controlling mitochondrial ß-oxidation in fasting animals. A peroxisome proliferator-activated receptor-alpha agonist and an inhibitor for peroxisomal ß-oxidation were administered to the fasting rats to investigate the role of dicarboxylic acids in liver fatty acid oxidation and lipid homeostasis. We observed that excessive ß-oxidation of endogenous dicarboxylic acids by peroxisomes generated considerable levels of succinate in the liver. Excessive succinate oxidation subsequently increased the mitochondrial NADH/NAD+ ratio and led to an accumulation of 3-OH-CoA and 2-enoyl-CoA intermediates in the liver. This further induced feedback suppression of mitochondrial ß-oxidation and promoted hepatic lipid deposition and steatosis. Specific inhibition of peroxisomal ß-oxidation attenuated fasting-induced lipid deposition in the liver by reducing succinate production and enhancing mitochondrial fatty acid oxidation. We conclude that suppression of mitochondrial ß-oxidation by oxidation of dicarboxylic acids serves as a mechanism for fasting-induced hepatic lipid accumulation and identifies cross talk between peroxisomal and mitochondrial fatty acid oxidation.


Subject(s)
Dicarboxylic Acids/chemistry , Fasting , Ketone Bodies/metabolism , Lipid Metabolism , Liver/metabolism , Mitochondria/metabolism , Peroxisomes/metabolism , Animals , Male , Oxidation-Reduction , Rats , Rats, Sprague-Dawley
19.
BMC Genom Data ; 22(1): 12, 2021 03 18.
Article in English | MEDLINE | ID: mdl-33736593

ABSTRACT

BACKGROUND: GATA1 is a key transcription factor in the GATA family, and promotes the differentiation and maturation of red blood cell, which is essential for normal hematopoiesis. RESULTS: Our results showed that the cDNA sequence of GATA1 was 2730 bp long encoding 443 amino acids. qRT-PCR analysis demonstrated that GATA1 had the highest expression in testis (T), followed by pituitary (P) and spleen (S). GATA1 gene expression in C. auratus red var. embryo from the neuroblast stage (N) to the embryo hatching (H) changes continuously; and the gene expression levels of nonylphenol (NP)-treated and those of control embryos were significantly different. Moreover, Methylation levels of GATA1 gene in NP-treated embryos were higher than those in control embryos, indicating that NP affected GATA1 methylation. CONCLUSIONS: Our study provides cues for further studying the roles of GATA1 gene in fish development, and suggested a potential molecular mechanism by which NP leads to abnormal development of fish embryos.


Subject(s)
Cloning, Molecular , GATA1 Transcription Factor/genetics , Gene Expression Profiling , Goldfish/classification , Goldfish/genetics , Animals , DNA, Complementary/genetics , Male
20.
Zhongguo Zhong Yao Za Zhi ; 46(1): 206-213, 2021 Jan.
Article in Chinese | MEDLINE | ID: mdl-33645072

ABSTRACT

This paper was to investigate the effect of Huanglian Jiedu Decoction(HLJD) on ulcerative colitis(UC) in mice, and determine the effective components in plasma, and virtually screen its therapeutic target, and predict its mechanism. Sixty Balb/c mice were randomly divided into blank group, model group, mesalazine treatment group(0.3 g·kg~(-1)), and HLJD treatment groups(24.66, 12.33, 6.17 g·kg~(-1)). Excepted for the blank group, all the mice in HLJD and mesalazine treatment groups were gavage administration. All mice freely drank 2.5% DSS solution for seven days to induce UC. The disease activity index(DAI) was detected each day. At the end of the experiment, HE staining was used to observe the pathological changes in colon. The content of IL-1ß, IL-6 and TNF-α in colon were determined by ELISA. The effective components in plasma were determined by UPLC-Q-TOF-MS. The reverse docking in PharmMapper was used to screen the component targets. The disease targets of UC were collected by searching TTD, OMIM and GeneCards databases. The intersection of the component targets and disease targets was selected as the therapeutic targets. Then the therapeutic targets were imported into the STRING for GO and KEGG enrichment analysis. Discovery Studio was used to simulate the docking between the components and the targets. RESULTS:: showed that the DAI in the model group increased significantly(P<0.05), and the number of inflammatory cells and infiltration degree increased significantly compared with the blank group. The DAI in HLJD treatment group was significantly reduced(P<0.05), and the number and infiltration degree of inflammatory cells were reduced compared with the model group. The ELISA results showed that the levels of IL-1ß, IL-6 and TNF-α were increased significantly in the model group(P<0.01) compared with the blank group, and significantly down regulated in the HLJD treatment group(P<0.05) compared with the model group. After UPLC-Q-TOF-MS analyse, ten components were identified. The network pharmacology analysis showed that the action targets were significantly enriched in 129 of biological processes, such as response to organic substance, chemical and oxygen-containing compound, etc., as well as 16 of signal pathways, such as IL-17, TNF and hepatitis B signal pathways, were enriched too. The results of molecular docking showed that limonin, palmatine and berberine could bind to CASP3 and MMP9 by hydrogen bond. In conclusion, HLJD could alleviate the colonic mucosal inflammatory infiltration and mucosal damage in UC mice. The mechanism may be related to the anti-inflammatory effect on UC mice by reducing the levels of IL-1ß, IL-6 and TNF-α in colon through limonin, palmatine and berberine regulating IL-17 signal pathway and TNF signal pathway via CASP3 and MMP9 meditated.


Subject(s)
Colitis, Ulcerative , Animals , Anti-Inflammatory Agents/therapeutic use , Colitis, Ulcerative/drug therapy , Colon , Dextran Sulfate/therapeutic use , Drugs, Chinese Herbal , Mice , Molecular Docking Simulation , Plasma
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