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Metabolic dysfunction-associated steatohepatitis (MASH) is a severe metabolic dysfunction-associated steatotic liver disease (MASLD) characterized by abnormal hepatic steatosis and inflammation. Previous studies have shown that Patchouli alcohol (PA), the primary component of Pogostemonis Herba, can alleviate digestive system diseases. However, its protection against MASH remains unclear. This study explored the protective effects and underlying mechanism of PA against high-fat diet-induced MASH in rats. Results showed that PA considerably reduced body weight, epididymal fat, and liver index and attenuated liver histological injury in MASH rats. PA alleviated hepatic injury by inhibiting steatosis and inflammation. These effects are associated with the improvement of SREBP-1c- and PPARα-mediated lipid metabolism and inhibition of the STING-signaling pathway-mediated inflammatory response. Moreover, PA-inhibited hepatic endoplasmic reticulum (ER) stress and mitochondrial dysfunction, reducing SREBP-1c and STING expressions and enhance PPARα expression. PA treatment had the strongest effect on the regulation of mitogen fusion protein 2 (Mfn2) in inhibiting mitochondrial dysfunction. Mfn2 is an important structural protein for binding ERs and mitochondria to form mitochondria-associated ER membranes (MAMs). MASH-mediated disruption of MAMs was inhibited after PA treatment-induced Mfn2 activation. Therefore, the pharmacological effect of PA on MASH is mainly attributed to the inhibition of MAM disruption-induced hepatic steatosis and inflammation. The findings of this study may have implications for MASH treatment that do not neglect the role of Mfn2-mediated MAMs.
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Dieta Hiperlipídica , Estresse do Retículo Endoplasmático , Retículo Endoplasmático , PPAR alfa , Ratos Sprague-Dawley , Sesquiterpenos , Animais , Masculino , Retículo Endoplasmático/metabolismo , Retículo Endoplasmático/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Ratos , Sesquiterpenos/uso terapêutico , Sesquiterpenos/farmacologia , PPAR alfa/metabolismo , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Fígado/patologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Fígado Gorduroso/tratamento farmacológico , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Metabolismo dos Lipídeos/efeitos dos fármacos , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/farmacologia , Inflamação/tratamento farmacológico , Pogostemon , Transdução de Sinais/efeitos dos fármacosRESUMO
INTRODUCTION: The postharvest physiological disorder known as 'black spot' in radish roots (Raphanus sativus) poses a significant challenge to quality maintenance during storage, particularly under summer conditions. The cause of this disorder, however, is poorly understood. OBJECTIVES: Characterize the underlying causes of 'black spot' disorder in radish roots and identify strategies to delay its onset. METHODS: Radish roots were placed in either polyvinyl chloride (PVC) or oriented polypropylene (OPP) packaging and stored for 4 days at 30 °C. Appearance and physiological parameters were assessed and transcriptomic and metabolomic analyses were conducted to identify the key molecular and biochemical factors contributing to the disorder and strategies for delaying its onset and development. RESULTS: OPP packaging effectively delayed the onset of 'black spot' in radishes, potentially due to changes in phenolic and lipid metabolism. Regarding phenolic metabolism, POD and PPO activity decreased, RsCCR and RsPOD expression was downregulated, genes involved in phenols and flavonoids synthesis were upregulated and their content increased, preventing the oxidative browning of phenols and generally enhancing stress tolerance. Regarding lipid metabolism, the level of alpha-linolenic acid increased, and genes regulating cutin and wax synthesis were upregulated. Notably, high flavonoid and low ROS levels collectively inhibited RsPLA2G expression, which reduced the production of arachidonic acid, pro-inflammatory compounds (LTA4 and PGG2), and ROS, alleviating the inflammatory response and oxidative stress in radish epidermal tissues. CONCLUSION: PVC packaging enhanced the postharvest onset of 'black spot' in radishes, while OPP packaging delayed both its onset and development. Our study provides insights into the response of radishes to different packaging materials during storage, and the causes and host responses that either enhance or delay 'black spot' disorder onset. Further studies will be conducted to confirm the molecular and biochemical processes responsible for the onset and development of 'black spot' in radishes.
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INTRODUCTION: The temperature control of magnetic hyperthermia therapy mainly relies on circulating water cooling and regulating magnetic field intensity, which increases complexity in clinical applications. Using magnetic materials with appropriate Curie temperature has become an effective means to solve temperature monitoring and potentially achieve self-regulating temperature. METHODS: A self-temperature-regulating Fe83Zr10B7 magnetic material was prepared. Based on this material, a simplified model of magnetic hyperthermia for arm tumors was established and verified using the finite- element method. The influence of magnetic field intensity and frequency on the heating power and temperature rise rate of different-sized and shaped magnetic media was studied. Additionally, factors such as the size, quantity, and spatial arrangement of the magnetic media were analyzed for their impact on the damage to tumors with different volumes and shapes. RESULTS: Spherical shape is the most suitable for magnetic hyperthermia media, and the radius of the spherical magnetic media can be chosen according to the size of the tumor. For tumors with a radius below 10 mm, using magnetic media with a particle size of 3.5 mm is recommended. The optimal magnetic field conditions are H0 (10-12 kA/m) and f (110-120 kHz). CONCLUSION: Based on the good magnetic properties and heating performance of the Fe83Zr10B7 magnetic material, it is feasible to use it as a magnetic medium for magnetic hyperthermia. The results of this study provide references for the selection of thermal seed size and magnetic field parameters in magnetic hyperthermia.
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Hipertermia Induzida , Neoplasias , Humanos , Temperatura , Hipertermia Induzida/métodos , Magnetismo , Neoplasias/terapia , Campos MagnéticosRESUMO
BACKGROUND: Lindera glauca with rich resource and fruit oil has emerged as novel source of biodiesel in China, but different germplasms show a variation for fruit oil content and FA profile. To develop L. glauca fruit oils as biodiesel, a concurrent exploration of oil content, FA composition, biodiesel yield, fuel property and prediction model construction was conducted on the fruits from 8 plus germplasms to select superior genotype for ideal biodiesel production. Another vital focus was to highlight mechanism that govern the differences in oil content and FA profile of different germplasms. The cross-accessions comparisons associated with oil-synthesized gene transcriptional level and oil accumulative amount led to the identification of potential determinants (enzymes, transporters or transcription factors) and regulatory mechanisms responsible for high-quality oil accumulation. RESULTS: To select superior germplasm and unravel regulatory mechanism of high oil production for developing L. glauca fruit oils as biodiesel, 8 plus trees (accession LG01/02/03/04/05/06/07/08) with high-yield fruits were selected to evaluate the differences in oil content, FA profile, biodiesel yield and fuel property, and to construct fuel property prediction model, revealing a variation in the levels of fruit oil (45.12-60.95%), monounsaturated FA (52.43-78.46%) and polyunsaturated FA (17.69-38.73%), and biodiesel yield (80.12-98.71%) across different accessions. Of note, LG06 had a maximum yield of oil (60.95%) and biodiesel (98.71%), and ideal proportions of C18:1 (77.89%), C18:2 (14.16%) and C18:3 (1.55%), indicating that fruit oils from accession LG06 was the most suitable for high-quality biodiesel production. To highlight molecular mechanism that govern such differences in oil content and FA composition of different accessions, the quantitative relationship between oil-synthesized gene transcription and oil accumulative amount were conducted on different accessions to identify some vital determinants (enzymes, transporters or transcription factors) with a model of carbon metabolic regulatory for high-quality oil accumulation by an integrated analysis of our recent transcriptome data and qRT-PCR detection. Our findings may present strategies for developing L. glauca fruit oils as biodiesel feedstock and engineering its oil accumulation. CONCLUSIONS: This is the first report on the cross-accessions evaluations of L. glauca fruit oils to determine ideal accession for producing ideal biodiesel, and the associations of oil accumulative amount with oil-synthesized gene transcription was performed to identify some crucial determinants (enzymes, transporters or transcription factors) with metabolic regulation model established for governing high oil production. Our finding may provide molecular basis for new strategies of developing biodiesel resource and engineering oil accumulation.
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ETHNOPHARMACOLOGICAL RELEVANCE: Initially recorded in Yifang Jijie (an ancient Chinese text), Qi Gong Wan (QGW) is used to treat obese women with infertility. QGW can help promote follicular development and maturation, regulate the balance of serum hormones between testosterone and estradiol, enhance endometrial receptivity, improve waist circumference, and ameliorate insulin resistance. It contains eight herbs: Pinellia ternata (Thunb.) Makino (Banxia), Citrus maxima (Burm.) (Juhong), Poria cocos (Schw.) Wolf. (Fuling), Atractylodes macrocephala Koidz (Baizhu), Cyperus rotundus L. (Xiangfu), Conioselinum anthriscoides 'Chuanxiong' (Chuanxiong), Massa Medicata Fermentata (Shenqu), and Glycyrrhiza uralensis Fisch. ex DC. (Gancao). However, the underlying mechanism of how QGW affects women with PCOS remains unclear. AIM OF THE STUDY: QGW has been widely used to treat PCOS patients with obesity clinically. This study was designed to identify its chemical and pharmacological properties. MATERIALS AND METHODS: Network pharmacology was used to predict the active compounds, potential targets, and pathways of QGW. Female C57BL/6J mice were injected with letrozole and fed a high-fat diet to establish a PCOS-insulin resistance (PCOS-IR) model. Body weight, estrous cycles, ovarian pathology, and serum insulin resistance were measured. qRT-PCR was used to examine the inflammation-related and steroid hormone biosynthesis-related mRNA expression in adipose tissue. Western blotting was used to determine the protein levels of Nrf2, HO-1, and Cyp1b1 in adipose tissue. Molecular docking was used to reveal the key chemical compounds of QGW. RESULTS: Network pharmacology revealed a total of 91 active ingredients in QGW that were associated with 167 targets. QGW could potentially treat PCOS-IR via nitrogen metabolism, steroid hormone biosynthesis, and ovarian steroidogenesis pathways. In the PCOS-IR mouse model, we found that QGW decreased the mean diameter of adipocytes and the total adipocyte area. Furthermore, QGW was found to significantly lower the expression of inflammation-related genes including TnfÉ and C4a/b and the steroid hormone biosynthesis-related gene Cyp1b1. QGW showed a tendency to improve cystic follicles, fasting insulin, and HOMA-IR index in the PCOS-IR mouse model. Combining these findings with the results of KEGG analysis, we conclude that QGW promotes the Nrf2/HO-1/Cyp1b1 pathway to protect adipose tissue under conditions of PCOS. Molecular docking revealed that rutin, nicotiflorin, and baicalein may be the key chemical compounds of QGW through which it improves adipocyte hypertrophy and inflammation. CONCLUSIONS: QGW improved adipocyte hypertrophy and inflammation in the PCOS-IR mouse model by activating the Nrf2/HO-1/Cyp1b1 pathway to protect adipose tissue. Our work thus provides a new research avenue for the study of traditional Chinese medicine in the treatment of PCOS.
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Resistência à Insulina , Síndrome do Ovário Policístico , Qigong , Animais , Feminino , Humanos , Camundongos , Adipócitos/metabolismo , Tecido Adiposo/metabolismo , Modelos Animais de Doenças , Estradiol , Hipertrofia/patologia , Inflamação/metabolismo , Insulina , Resistência à Insulina/fisiologia , Camundongos Endogâmicos C57BL , Simulação de Acoplamento Molecular , Farmacologia em Rede , Fator 2 Relacionado a NF-E2/metabolismo , Obesidade/metabolismo , Síndrome do Ovário Policístico/tratamento farmacológicoRESUMO
Objective: This investigation was conducted to analyze and evaluate the impact of Chinese herbal medicine on glucolipid metabolism in women with polycystic ovary syndrome (PCOS). Methods: We used manual and computer-aided search methods, and the search scopes included Chinese databases (China National Knowledge Infrastructure, Wanfang, the China Science and Technology Journal Database, and the Chinese Biomedical Literature Database) and English databases (PubMed, Embase, Web of Science, and the Cochrane Library). We searched these eight databases for randomized controlled trials investigating the effects of Chinese herbal medicine on glucolipid metabolism in women with PCOS, with the retrieval deadline being June 2021. Two reviewers screened, selected, and extracted data and verified the results independently. The NoteExpress software was used to manage and screen the literature, the risk of bias assessment tool was used to evaluate the methodological quality of the included studies, and the RevMan 5.4 software was used for meta-analysis. Results: A total of 13 trials were included, including 825 patients with PCOS. Because the drugs used in the control group were different, we divided the results into two parts, with four trials using placebo and nine trials using metformin as the control. The results of the meta-analysis showed that fasting insulin (MD = -2.45, 95% CI = [-4.74, -0.17], P = 0.04), 2 h fasting plasma glucose (MD = -0.33, 95% CI = [-0.64, -0.02], P = 0.04), serum total cholesterol (MD = -0.38, 95% CI = [-0.58, -0.18], P = 0.0002), triglycerides (MD = -0.36, 95% CI = [-0.58, -0.14], P = 0.001), and low-density lipoprotein cholesterol (MD = -0.58, 95% CI = [-0.75, -0.41], P < 0.00001) were significantly improved in the Chinese herbal medicine group compared with the placebo group. In addition, compared with metformin, body mass index (MD = -1.04, 95% CI = [-1.55, -0.53], P < 0.0001), serum total cholesterol (MD = -0.27, 95% CI = [-0.46, -0.07] P = 0.007), and low-density lipoprotein cholesterol were significantly reduced (MD = -0.12, 95% CI = [-0.22, -0.02], P = 0.02) and high-density lipoprotein cholesterol (MD = 0.09, 95% CI = [0.02, 0.17], P = 0.01) was significantly improved after treatment with Chinese herbal medicine. Conclusion: Compared with the placebo group, Chinese herbal medicine had positive effects on glucolipid metabolism in women with PCOS. Chinese herbal medicine had a positive effect on lipid metabolism when the control group was metformin, but no effect on glucose metabolism. These findings need to be verified in high-quality, large-sample, randomized controlled trials in the future.
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We have developed a new method for selecting the test color sample set (TCSS) used to calculate CIE 2017 color fidelity index (CIE-Rf). Taking a Large Set as a starting point, a new optimized color sample set (OCSS) is obtained by clustering analysis. Taking metamerism phenomenon into account, spectra clustering is performed within the class obtained from color appearance attributes clustering. The CIE-Rf of 1202 light sources are calculated and analyzed by taking the Large Set, OCSS and CIE color evaluation sample set (CIE CESS-99) as TCSS. Through analyzing CIE-Rf, the performance of the OCSS is further investigated. The results show that the clustering analysis method developed in this paper can be well used in selecting test color samples, and the obtained OCSS can represent Large Set well and be better used for color fidelity metrics of light sources.
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Diabetes is a complex illness requiring long-term therapy. Cyclocarya paliurus, a recently confirmed new food resource, shows significant hypoglycemic and hypolipidemic effects in type II diabetes. Triterpenoid saponins are considered as the effective medicinal components of C. paliurus and are useful for the treatment of diabetes mellitus. However, little is known regarding their specific mechanism of actions. In this study, we used active ingredient screening and target prediction techniques to determine the components of C. paliurus responsible for its anti-diabetic effects as well as their targets. In addition, we used bioinformatics technology and molecular docking analysis to determine the mechanisms underlying their anti-diabetic effects. A total of 39 triterpenes were identified through a literature search and 1 triterpene compound by experiments. In all, 33 potential target proteins associated with 36 pathways were predicted to be related to diabetes. Finally, 7 compounds, 15 target proteins, and 15 signaling pathways were found to play important roles in the therapeutic effects of C. paliurus against diabetes. These results provide a theoretical framework for the use of C. paliurus against diabetes. Moreover, molecular docking verification showed that more than 90% of the active ingredients had binding activity when tested against key target proteins, and a literature search showed that the active ingredients identified had anti-diabetic effects, indicating that the results were highly reliable.
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BACKGROUND: Based on our previous studies of 17 Prunus sibirica germplasms, one plus tree with high quality and quantity of seed oils has emerged as novel potential source of biodiesel. To better develop P. sibirica seed oils as woody biodiesel, a concurrent exploration of oil content, FA composition, biodiesel yield and fuel properties as well as prediction model construction for fuel properties was conducted on developing seeds to determine the optimal seed harvest time for producing high-quality biodiesel. Oil synthesis required supply of carbon source, energy and FA, but their transport mechanisms still remains enigmatic. Our recent 454 sequencing of P. sibirica could provide long-read sequences to identify membrane transporters for a better understanding of regulatory mechanism for high oil production in developing seeds. RESULTS: To better develop the seed oils of P. sibirica as woody biodiesel, we firstly focused on a temporal and comparative evaluation of growth tendency, oil content, FA composition, biodiesel yield and fuel properties as well as model construction for biodiesel property prediction in different developing seeds from P. sibirica plus tree (accession AS-80), revealing that the oils from developing seeds harvested after 60 days after flowering (DAF) could be as novel potential feedstock for producing biodiesel with ideal fuel property. To gain new insight into membrane transport mechanism for high oil yield in developing seeds of P. sibirica, we presented a global analysis of transporter based on our recent 454 sequencing data of P. sibirica. We annotated a total of 116 genes for membrane-localized transporters at different organelles (plastid, endoplasmatic reticulum, tonoplast, mitochondria and peroxisome), of which some specific transporters were identified to be involved in carbon allocation, metabolite transport and energy supply for oil synthesis by both RT-PCR and qRT-PCR. Importantly, the transporter-mediated model was well established for high oil synthesis in developing P. sibirica seeds. Our findings could help to reveal molecular mechanism of increased oil production and may also present strategies for engineering oil accumulation in oilseed plants. CONCLUSIONS: This study presents a temporal and comparative evaluation of developing P. sibirica seed oils as a potential feedstock for producing high-quality biodiesel and a global identification for membrane transporters was to gain better insights into regulatory mechanism of high oil production in developing seeds of P. sibirica. Our findings may present strategies for developing woody biodiesel resources and engineering oil accumulation.
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BACKGROUND: Lindera glauca fruit with high quality and quantity of oil has emerged as a novel potential source of biodiesel in China, but the molecular regulatory mechanism of carbon flux and energy source for oil biosynthesis in developing fruits is still unknown. To better develop fruit oils of L. glauca as woody biodiesel, a combination of two different sequencing platforms (454 and Illumina) and qRT-PCR analysis was used to define a minimal reference transcriptome of developing L. glauca fruits, and to construct carbon and energy metabolic model for regulation of carbon partitioning and energy supply for FA biosynthesis and oil accumulation. RESULTS: We first analyzed the dynamic patterns of growth tendency, oil content, FA compositions, biodiesel properties, and the contents of ATP and pyridine nucleotide of L. glauca fruits from seven different developing stages. Comprehensive characterization of transcriptome of the developing L. glauca fruit was performed using a combination of two different next-generation sequencing platforms, of which three representative fruit samples (50, 125, and 150 DAF) and one mixed sample from seven developing stages were selected for Illumina and 454 sequencing, respectively. The unigenes separately obtained from long and short reads (201, and 259, respectively, in total) were reconciled using TGICL software, resulting in a total of 60,031 unigenes (mean length = 1061.95 bp) to describe a transcriptome for developing L. glauca fruits. Notably, 198 genes were annotated for photosynthesis, sucrose cleavage, carbon allocation, metabolite transport, acetyl-CoA formation, oil synthesis, and energy metabolism, among which some specific transporters, transcription factors, and enzymes were identified to be implicated in carbon partitioning and energy source for oil synthesis by an integrated analysis of transcriptomic sequencing and qRT-PCR. Importantly, the carbon and energy metabolic model was well established for oil biosynthesis of developing L. glauca fruits, which could help to reveal the molecular regulatory mechanism of the increased oil production in developing fruits. CONCLUSIONS: This study presents for the first time the application of an integrated two different sequencing analyses (Illumina and 454) and qRT-PCR detection to define a minimal reference transcriptome for developing L. glauca fruits, and to elucidate the molecular regulatory mechanism of carbon flux control and energy provision for oil synthesis. Our results will provide a valuable resource for future fundamental and applied research on the woody biodiesel plants.
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Recently, our transcriptomic analysis has identified some functional genes responsible for oil biosynthesis in developing SASK, yet miRNA-mediated regulation for SASK development and oil accumulation is poorly understood. Here, 3 representative periods of 10, 30 and 60 DAF were selected for sRNA sequencing based on the dynamic patterns of growth tendency and oil content of developing SASK. By miRNA transcriptomic analysis, we characterized 296 known and 44 novel miRNAs in developing SASK, among which 36 known and 6 novel miRNAs respond specifically to developing SASK. Importantly, we performed an integrated analysis of mRNA and miRNA transcriptome as well as qRT-PCR detection to identify some key miRNAs and their targets (miR156-SPL, miR160-ARF18, miR164-NAC1, miR171h-SCL6, miR172-AP2, miR395-AUX22B, miR530-P2C37, miR393h-TIR1/AFB2 and psi-miRn5-SnRK2A) potentially involved in developing response and hormone signaling of SASK. Our results provide new insights into the important regulatory function of cross-talk between development response and hormone signaling for SASK oil accumulation.