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1.
Stem Cells Int ; 2024: 5388064, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38633381

RESUMO

Objectives: Traditional Chinese medicine Cortex Eucommiae has been used to treat bone fracture for hundreds of years, which exerts a significant improvement in fracture healing. Aucubin, a derivative isolated from Cortex Eucommiae, has been demonstrated to possess anti-inflammatory, immunoregulatory, and antioxidative potential. In the present study, our aim was to explore its function in bone regeneration and elucidate the underlying mechanism. Materials and Methods: The effects of Aucubin on osteoblast and osteoclast were examined in mouse bone marrow-derived mesenchymal stem cells (BM-MSCs) and RAW 264.7 cells, respectively. Moreover, the lncRNA H19 and Wnt/ß-catenin signaling were detected by qPCR examination, western blotting, and luciferase activity assays. Using the femur fracture mice model, the in vivo effect of Aucubin on bone formation was monitored by X-ray, micro-CT, histomorphometry, and immunohistochemistry staining. Results: In the present study, Aucubin was found to significantly promote osteogenic differentiation in vitro and stimulated bone formation in vivo. Regarding to the underlying mechanism, H19 was found to be obviously upregulated by Aucubin in MSCs and thus induced the activation of Wnt/ß-catenin signaling. Moreover, H19 knockdown partially reversed the Aucubin-induced osteogenic differentiation and successfully suppressed the activation of Wnt/ß-catenin signaling. We therefore suggested that Aucubin induced the activation of Wnt/ß-catenin signaling through promoting H19 expression. Conclusion: Our results demonstrated that Aucubin promoted osteogenesis in vitro and facilitated fracture healing in vivo through the H19-Wnt/ß-catenin regulatory axis.

2.
J Pharm Biomed Anal ; 243: 116077, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38460276

RESUMO

BACKGROUND: Dendrobium officinale Kimura et Migo (DO), a valuable Chinese herbal medicine, has been reported to exhibit potential effects in the prevention and treatment of lung cancer. However, its material basis and mechanism of action have not been comprehensively analyzed. PURPOSE: The objective of this study was to preliminarily elucidate the active components and pharmacological mechanisms of DO in treating lung cancer, according to UPLC-Q/TOF-MS, HPAEC-PAD, network pharmacology, molecular docking, and experimental verification. METHODS: The chemical components of DO were identified via UPLC-Q/TOF-MS, while the monosaccharide composition of Dendrobium officinale polysaccharide (DOP) was determined by HPAEC-PAD. The prospective active constituents of DO as well as their respective targets were predicted in the combined database of Swiss ADME and Swiss Target Prediction. Relevant disease targets for lung cancer were searched in OMIM, TTD, and Genecards databases. Further, the active compounds and potential core targets of DO against lung cancer were found by the C-T-D network and the PPI network, respectively. The core targets were then subjected to enrichment analysis in the Metascape database. The main active compounds were molecularly docked to the core targets and visualized. Finally, the viability of A549 cells and the relative quantity of associated proteins within the major signaling pathway were detected. RESULTS: 249 ingredients were identified from DO, including 39 flavonoids, 39 bibenzyls, 50 organic acids, 8 phenanthrenes, 27 phenylpropanoids, 17 alkaloids, 17 amino acids and their derivatives, 7 monosaccharides, and 45 others. Here, 50 main active compounds with high degree values were attained through the C-T-D network, mainly consisting of bibenzyls and monosaccharides. Based on the PPI network analysis, 10 core targets were further predicted, including HSP90AA1, SRC, ESR1, CREBBP, MAPK3, AKT1, PIK3R1, PIK3CA, HIF1A, and HDAC1. The results of the enrichment analysis and molecular docking indicated a close association between the therapeutic mechanism of DO and the PI3K-Akt signaling pathway. It was confirmed that the bibenzyl extract and erianin could inhibit the multiplication of A549 cells in vitro. Furthermore, erianin was found to down-regulate the relative expressions of p-AKT and p-PI3K proteins within the PI3K-Akt signaling pathway. CONCLUSIONS: This study predicted that DO could treat lung cancer through various components, multiple targets, and diverse pathways. Bibenzyls from DO might exert anti-lung cancer activity by inhibiting cancer cell proliferation and modulating the PI3K-Akt signaling pathway. A fundamental reference for further studies and clinical therapy was given by the above data.


Assuntos
Bibenzilas , Dendrobium , Medicamentos de Ervas Chinesas , Neoplasias Pulmonares , Fenol , Neoplasias Pulmonares/tratamento farmacológico , Farmacologia em Rede , Simulação de Acoplamento Molecular , Fosfatidilinositol 3-Quinases , Estudos Prospectivos , Proteínas Proto-Oncogênicas c-akt , Monossacarídeos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico
3.
Food Chem ; 445: 138765, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38367562

RESUMO

This study aimed to reveal the effects and regulatory mechanism of dietary NDF on the performance of pigs by multi-omics analysis. Results showed that 16 % dietary NDF significantly improved meat quality, increased flavor amino acid content, and reduced backfat thickness and the feed-to-gain ratio. 16S rDNA sequencing showed that 16 % NDF significantly increased the abundance of Akkermansia, Lachnoclostridium, and Ruminococcus. Transcript analysis showed that genes related to muscle development and lipid metabolism were significantly modified. Metabonomic analysis showed that 16 % NDF significantly increased amino and fatty acid related metabolites. Correlation analysis suggested that 16 % NDF treatment may alter the gut microbiota and metabolites, regulate the expression of genes related to lipid and amino metabolism, and ultimately affect the flavor and performance of pigs. This study provides a novel understanding about the effect and regulatory mechanism of NDF supplements on the finishing pigs and a relevant reference for the improvement of diet formulation.


Assuntos
Aminoácidos , Detergentes , Suínos/genética , Animais , Aminoácidos/metabolismo , Multiômica , Composição Corporal , Suplementos Nutricionais , Dieta/veterinária , Carne/análise , Ração Animal/análise
4.
Am J Chin Med ; 51(8): 1927-1955, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37930334

RESUMO

Depression is a highly heterogeneous mental illness. Drug treatment is currently the main therapeutic strategy used in the clinic, but its efficacy is limited by the modulation of a single target, slow onset, and side effects. The gut-brain axis is of increasing interest because intestinal microenvironment disorders increase susceptibility to depression. In turn, depression affects intestinal microenvironment homeostasis by altering intestinal tissue structure, flora abundance and metabolism, hormone secretion, neurotransmitter transmission, and immune balance. Depression falls into the category of "stagnation syndrome" according to Traditional Chinese Medicine (TCM), which further specifies that "the heart governs the spirit and is exterior-interior with the small intestine". However, the exact mechanisms of the means by which the disordered intestinal microenvironment affects depression are still unclear. Here, we present an overview of how the Chinese materia medica (CMM) protects against depression by repairing intestinal microenvironment homeostasis. We review the past five years of research progress in classical antidepressant TCM formulae and single CMMs on regulating the intestinal microenvironment for the treatment of depression. We then analyze and clarify the multitarget functions of CMM in repairing intestinal homeostasis and aim to provide a new theoretical basis for CMM clinical application in the treatment of depression.


Assuntos
Medicamentos de Ervas Chinesas , Materia Medica , Materia Medica/uso terapêutico , Depressão/tratamento farmacológico , Medicina Tradicional Chinesa , Transporte Biológico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico
5.
EMBO Mol Med ; 15(11): e18367, 2023 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-37859621

RESUMO

Clinical and preclinical studies established that supplementing diets with ω3 polyunsaturated fatty acids (PUFA) can reduce hepatic dysfunction in nonalcoholic steatohepatitis (NASH) but molecular underpinnings of this action were elusive. Herein, we used multi-omic network analysis that unveiled critical molecular pathways involved in ω3 PUFA effects in a preclinical mouse model of western diet induced NASH. Since NASH is a precursor of liver cancer, we also performed meta-analysis of human liver cancer transcriptomes that uncovered betacellulin as a key EGFR-binding protein upregulated in liver cancer and downregulated by ω3 PUFAs in animals and humans with NASH. We then confirmed that betacellulin acts by promoting proliferation of quiescent hepatic stellate cells, inducing transforming growth factor-ß2 and increasing collagen production. When used in combination with TLR2/4 agonists, betacellulin upregulated integrins in macrophages thereby potentiating inflammation and fibrosis. Taken together, our results suggest that suppression of betacellulin is one of the key mechanisms associated with anti-inflammatory and anti-fibrotic effects of ω3 PUFA on NASH.


Assuntos
Ácidos Graxos Ômega-3 , Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Humanos , Animais , Camundongos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/patologia , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Ômega-3/uso terapêutico , Ácidos Graxos Ômega-3/metabolismo , Dieta Ocidental , Betacelulina/metabolismo , Multiômica , Fibrose , Neoplasias Hepáticas/patologia , Fígado/patologia , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL
6.
Int J Mol Sci ; 24(13)2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-37446145

RESUMO

As an important medicinal and aromatic plant, patchouli is distributed throughout most of Asia. However, current research on patchouli's genetic diversity is limited and lacks genome-wide studies. Here, we have collected seven representative patchouli accessions from different localities and performed whole-genome resequencing on them. In total, 402,650 single nucleotide polymorphisms (SNPs) and 153,233 insertions/deletions (INDELs) were detected. Based on these abundant genetic variants, patchouli accessions were primarily classified into the Chinese group and the Southeast Asian group. However, the accession SP (Shipai) collected from China formed a distinct subgroup within the Southeast Asian group. As SP has been used as a genuine herb in traditional Chinese medicine, its unique molecular markers have been subsequently screened and verified. For 26,144 specific SNPs and 16,289 specific INDELs in SP, 10 of them were validated using Polymerase Chain Reaction (PCR) following three different approaches. Further, we analyzed the effects of total genetic variants on genes involved in the sesquiterpene synthesis pathway, which produce the primary phytochemical compounds found in patchouli. Eight genes were ultimately investigated and a gene encoding nerolidol synthetase (PatNES) was chosen and confirmed through biochemical assay. In accession YN, genetic variants in PatNES led to a loss of synthetase activity. Our results provide valuable information for understanding the diversity of patchouli germplasm resources.


Assuntos
Pogostemon , Pogostemon/genética , Análise de Sequência de DNA , Polimorfismo de Nucleotídeo Único , Genoma de Planta , Ásia
7.
J Orthop Translat ; 39: 34-42, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36636358

RESUMO

Background: Osteosarcoma (OS) is the most common primary malignancy in bone tissues, and effective therapeutics remain absent in clinical practice. Traditional Chinese medicines (TCM) have been used for thousands of years, which provide great insights into OS management. Gallic acid (GA) is a natural phenolic acid enriched in various foods and herbs. Several pharmacological activities of GA such as anti-oxidation and anti-inflammation have been well-established. However, its biological function in OS remains not fully understood. Methods: The potential anti-cancer properties of GA were evaluated in 143 â€‹B, U2OS and MG63 â€‹cells. Its effects on cell growth, cell cycle, apoptosis and migration were examined in these OS cells. The lncRNA H19 and Wnt/ß-catenin signaling were detected by qPCR, luciferase activity and Western blotting assays. The in vivo effect of GA on tumor growth was investigated using an orthotopic mouse model. Results: In the present study, GA was found to suppress the tumor growth in vitro via inducing cell cycle arrest and apoptosis in OS cells, and inhibit the invasion and metastasis as well. Using the orthotopic animal model, GA was also found to suppress tumorigenesis in vivo. Long noncoding RNA (lncRNA) H19 was demonstrated to be down-regulated by GA, and thus disrupted the canonical Wnt/ß-catenin signaling in OS cells. Furthermore, the ectopic expression of H19 rescued the GA-induced suppressive effects on tumor growth and metastasis, and partially reversed the inactivation of Wnt/ß-catenin signaling. Conclusions: Taken together, our results indicated that GA inhibited tumor growth through an H19-mediated Wnt/ß-catenin signaling regulatory axis in OS cells. The translational potential of this article: The information gained from this study provides a novel underlying mechanism of GA mediated anti-OS activity, suggesting that GA may be a promising drug candidate for OS patients.

8.
Poult Sci ; 102(3): 102454, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36682129

RESUMO

Diet may affect gut microbial composition and diversity. There were 3 dietary groups: 0% citrus pulp diet (C), 1.5% citrus pulp diet (I), and 2.5% citrus pulp diet (II). A total of 180 healthy AA broilers (21-day old) were divided into 3 groups (C, I, and II), each group was set up with 6 replicates, and each replicate including 10 broilers (half male and female). At 42 d, the cecal contents of 18 broiler chickens were collected after slaughter. The cecal contents were analyzed using 16S rRNA sequencing technology. Compared with group C, the abundance of Firmicutes in groups I and II decreased, while the relative abundances of Bacteroidetes, Verrucomicrobia, Lactobacillus, and Faecalibacterium increased. LEfSe analysis showed that Actinobacteria, Coriobacteriia, Coriobacteriales, and Ruminococcaceae_bacterium_Marseille_P2935 in group I were significantly higher than those in group C. Bacteria, Coriobacteriales, Coriobacteriia, Coriobacteriaceae, Slackia, Bacteroides_sp_Marseille_P3132, and Lactobacillus_pontis in group II were significantly higher than those in group C. The Staphylococcaceae, Bacteroides_sp_Marseille_P3132, Macroccus, Lactobacillus_pontis, and Streptococcus_equinus in group II were significantly higher than those in group I. Functional predictions indicated that the cecal microbiota of broilers fed the 2.5% citrus pulp diet was more tend to utilize carbohydrates through glycolytic/gluconeogenesis metabolism. Adding citrus pulp to the diet affects the microbial composition and has important implications for studying gut health and improving economic benefits.


Assuntos
Galinhas , Dieta , Animais , Masculino , Feminino , Galinhas/genética , RNA Ribossômico 16S/genética , Dieta/veterinária , Ceco/microbiologia , Bactérias , Ração Animal/análise , Suplementos Nutricionais
9.
J Mater Chem B ; 11(2): 415-429, 2023 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-36512437

RESUMO

Ferroptosis, a type of programmed cell death induced by the iron-dependent lipid hydroperoxide pathway, has attracted widespread attention. However, Fenton response-dependent ferroptosis has many limitations, such as insufficient reaction conditions in the tumor micro-environment. Here, we propose an all-in-one phototherapy nanoplatform consisting of iron-polydopamine (Fe-PDA), a folic acid-modified red blood cell membrane (FA-RBCm), and epirubicin (EPI), namely, Fe-PDA-EPI@FA-RBCm NPs, to achieve enhanced photothermal-ferroptosis effects via overcoming the limitations of the Fenton-like reaction. The results showed that the synthesized biomimetic nanoparticles could decompose hydrogen peroxide (H2O2) to generate hydroxyl radicals (˙OH), and further induce the non-apoptotic ferroptosis pathway. After irradiation with near-infrared (NIR) light, the uptake of Fe-PDA-EPI@FA-RBCm NPs by cells could be effectively promoted, and it presented impressive in vitro and in vivo photothermal properties. In vitro and in vivo results showed that laser irradiation could enhance ferroptosis by promoting the production of reactive oxygen species (ROS) and lipid peroxides, down-regulating the expression of glutathione peroxidase 4 (GPX4), and reducing the mitochondrial membrane potential. Furthermore, the photothermal-promoted ferroptosis and apoptosis pathways (photothermal therapy and chemotherapy) exhibited outstanding synergistic antitumor efficacy in vitro and in vivo, with an in vivo tumor inhibition rate as high as 76.95%. In conclusion, the construction of tumor-targeted biomimetic nanocarriers utilizing the advantageous properties of RBCm has been investigated as a potential anticancer strategy.


Assuntos
Ferroptose , Nanopartículas , Neoplasias , Peróxido de Hidrogênio/farmacologia , Nanopartículas/uso terapêutico , Apoptose , Epirubicina/farmacologia , Ferro/farmacologia
10.
Artigo em Inglês | MEDLINE | ID: mdl-36267093

RESUMO

Calycosin (CA) is a flavonoid extracted from the root of Astragalus membranaceus and has antioxidant, anti-inflammation, and antiapoptosis properties. The objective of this study was to investigate the efficacy of CA in protecting against pulmonary fibrosis. CA (14 mg/kg) and SB216763 (20 mg/kg) were administrated to bleomycin-induced pulmonary fibrosis mice for 3 weeks. The results concluded that CA alleviated the inflammation and collagen deposition in pulmonary fibrosis. In addition, CA reduced MDA level, enhanced SOD and TAC activities, and increased the activity of the Nrf2/HO-1 pathway. CA also regulated the expressions of apoptosis-related proteins. Moreover, CA enhanced autophagy via upregulating LC3, beclin1, PINK1, and reducing p62. CA also increased expression of LAMP1 and TFEB, and inhibited the release of lysosome enzymes from ruptured lysosomes. These results provide new evidence that CA protects against pulmonary fibrosis through inhibiting oxidative stress and apoptosis. In addition, autophagy abnormality and lysosome dysfunction are restored by CA.

11.
Artigo em Inglês | MEDLINE | ID: mdl-35921699

RESUMO

Er-Zhi-Wan (EZW), a classical traditional Chinese formulation, has attracted more and more attention. This study was carried out to analyze the constituents of EZW absorbed into blood and find out the potential active ingredients for treating osteoporosis (OP) with kidney-yin deficiency (KYD). The rat model of OP with KYD was achieved by ovariectomies and using the mixture of thyroxine and reserpine. Then ultra-high performance liquid chromatography coupled with a quadrupole time-of-flight mass spectrometer (UPLC-Q/TOF-MS) combined with statistical analysis was used to analyze the constituents of EZW absorbed into blood and differential components between the normal and OP with KYD rats. Finally, the components identified in OP with KYD rats were docked with targets of OP with KYD found in online databases. The results of molecular docking were adopted to find the potential active ingredients and further verified in vitro experiment. A total of 21 prototype compounds and 69 metabolites were identified in serum. Among them, 63 components in model rats and 50 components in normal rats were summarized, respectively. Most of the identified metabolites in serum of model rats were produced by hydrolysis, oxidation or glucuronidation, while in serum of normal rats were produced by hydrolysis, oxidation and methylation. According to the results of molecular docking, specnuezhenide, salidroside, tyrosol, echinacoside and verbascoside could be classified as potential active ingredients. The activity of salidroside and a metabolite was verified by pharmacodynamics analysis. In summary, UPLC-Q/TOF-MS system was combined with molecular docking to search the potential active ingredients from model rats of OP with KYD, which provided a new idea for the research on the pharmacodynamic material basis of other traditional medicine. Moreover, the result of this study lays the foundation for further study regarding the mechanism of EZW in treating OP with KYD.


Assuntos
Medicamentos de Ervas Chinesas , Osteoporose , Animais , China , Cromatografia Líquida de Alta Pressão/métodos , Rim/química , Simulação de Acoplamento Molecular , Ratos , Deficiência da Energia Yin
12.
Front Pharmacol ; 13: 921209, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35903328

RESUMO

Number 2 Feibi Recipe (N2FBR) is a traditional Chinese medicine formula for treating idiopathic pulmonary fibrosis. N2FBR inhibits H2O2-mediated oxidative stress damage in alveolar epithelial cells by increasing autophagy, as we previously demonstrated. However, it is unknown if similar mechanisms occur in vivo. We established a pulmonary fibrosis model by instilling bleomycin (BLM) from the airway to examine the effects of N2FBR on pulmonary fibrosis and investigate its probable mechanism in this work. We discovered that N2FBR treatment effectively alleviated interstitial fibrosis as well as collagen deposition, primarily in upregulating SOD, GSH-Px, T-AOC and downregulating MDA content. N2FBR also increased the expression of LC3B, Beclin-1, LAMP1, TFEB and downregulated the expression of p62, legumain. N2FBR treatment boosted the production of autophagosomes, according to the results of the TEM observation. Furthermore, we explored that N2FBR exerted its anti-oxidative stress and pro-autophagy effects via GSK-3ß/mTOR signalling pathway. Therefore, these results provide further evidence for the protective effect of N2FBR in pulmonary fibrosis. Our findings could have ramifications for the development of antifibrosis therapies.

13.
Front Physiol ; 13: 897458, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35694407

RESUMO

Medical leeches are widely been used in biochemical and clinical medical studies, helping to restore blood circulation to grafted or severely injured tissue. Mostly, adult leeches are being used in the traditional pharmacopeia, but the gene expression profiling of leeches in different growth periods is not well-reported. So, in this study, we used transcriptome analysis to analyze the comparative gene expression patterns of Hirudinaria manillensis (H. manillensis) in different growth periods, including larval, young, and adult stages. We constructed 24 cDNA libraries from H. manillensis larval, young, and adult stages, and about 54,639,118 sequences were generated, 18,106 mRNA transcripts of which 958 novel mRNAs and 491 lncRNAs were also assembled as well. Furthermore, the results of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed that the differentially upregulated genes from the larval to adult stages were enriched in pathways such as cilium, myofibril, contractile fiber, cytoskeleton proteins, dilated cardiomyopathy, adrenergic signaling in cardiomyocytes, etc. Moreover, in the adult stages, a significant increase in the expression of the Hirudin-HM (HIRM2) genes was detected. In addition, our comparative transcriptome profiling data from different growth stages of H. manillensis also identified a large number of DEGs and DElncRNAs which were tentatively found to be associated with the growth of H. manillensis; as it grew, the muscle-related gene expression increased, while the lipid metabolism and need for stimulation and nutrition-related genes decreased. Similarly, the higher expression of HIRM2 might attribute to the high expression of protein disulfide isomerase gene family (PDI) family genes in adulthood, which provides an important clue that why adult leeches rather than young leeches are widely used in clinical therapeutics and traditional Chinese medicine.

14.
Carbohydr Polym ; 292: 119653, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-35725160

RESUMO

Gut barrier makes a huge research gap between in vivo and in vitro studies of orally bioactive polysaccharides: whether/how they contact the related cells in vivo. A hyperbranched heteroglycan RAP from Radix Astragali, exerting antitumor and immunomodulatory effects in vitro and in vivo, is right an example. Here, we determined first that RAP's antitumor activity is immune-dependent. Being undegraded and non-absorbing, RAP quickly entered Peyer's patches (PPs) in 1 h where it directly targeted follicle dendritic cells and initiated antitumor immune responses. RAP was further delivered to mesenteric lymph node, bone marrow, and tumor. By contrast, the control Dendrobium officinale polysaccharide did not enter PPs. These findings revealed a blood/microbiota-independent and selective lymphatic route for orally administrated RAP to directly contact immune cells and trigger antitumor immune responses. This route bridges the research gap between the in vitro and in vivo studies and might apply to many other bioactive polysaccharides.


Assuntos
Medicamentos de Ervas Chinesas , Nódulos Linfáticos Agregados , Astragalus propinquus , Imunidade , Polissacarídeos/metabolismo , Polissacarídeos/farmacologia
15.
Nat Chem Biol ; 18(7): 751-761, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35637349

RESUMO

The selenoprotein glutathione peroxidase 4 (GPX4) prevents ferroptosis by converting lipid peroxides into nontoxic lipid alcohols. GPX4 has emerged as a promising therapeutic target for cancer treatment, but some cancer cells are resistant to ferroptosis triggered by GPX4 inhibition. Using a chemical-genetic screen, we identify LRP8 (also known as ApoER2) as a ferroptosis resistance factor that is upregulated in cancer. Loss of LRP8 decreases cellular selenium levels and the expression of a subset of selenoproteins. Counter to the canonical hierarchical selenoprotein regulatory program, GPX4 levels are strongly reduced due to impaired translation. Mechanistically, low selenium levels result in ribosome stalling at the inefficiently decoded GPX4 selenocysteine UGA codon, leading to ribosome collisions, early translation termination and proteasomal clearance of the N-terminal GPX4 fragment. These findings reveal rewiring of the selenoprotein hierarchy in cancer cells and identify ribosome stalling and collisions during GPX4 translation as ferroptosis vulnerabilities in cancer.


Assuntos
Ferroptose , Selênio , Fosfolipídeo Hidroperóxido Glutationa Peroxidase , Ribossomos/metabolismo , Selênio/metabolismo , Selênio/farmacologia , Selenoproteínas/genética
16.
Water Sci Technol ; 85(9): 2601-2612, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35576255

RESUMO

This study involved a comprehensive renovation of fish ponds to improve the water quality of a eutrophic river in Dongguan City. The abandoned fish ponds were transformed into three different types of stabilization ponds: facultative, aerated biological, and submerged plant stabilization ponds. The water of the eutrophic section of the river was pumped into the facultative stabilization pond and discharged into the Haizai River through an aerated biological pond and a submerged plant pond. In the aerated biological pond, secondary treatment was carried out using plant zoning and artificial floating island aeration system. The submerged plant pond used fountain-type aeration and an underwater forest for tertiary treatment. After four months of monitoring the water quality of the stabilization pond and the river, the ammonia nitrogen (NH3-N), total phosphorus (TP), and chemical oxygen demand (CODCr) levels in the raw sewage reduced from 6.53 mg/L to 1.13 mg/L, 1.76 mg/L to 0.29 mg/L, and 63 mg/L to 22 mg/L, respectively; the transparency of water increased to 45 cm, and dissolved oxygen (DO) level increased to 5.32 mg/L. This study provides a reference for the ex-situ treatment of urban eutrophic waterbodies.


Assuntos
Lagoas , Esgotos , Animais , Análise da Demanda Biológica de Oxigênio , Nitrogênio/análise , Fósforo/análise
17.
Mar Drugs ; 20(4)2022 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-35447920

RESUMO

Alzheimer´s disease is a global neurodegenerative health concern. To prevent the disease, the simultaneous inhibition of acetylcholinesterase and oxidative stress is an efficient approach. In this study, the inhibition effect of all-trans astaxanthin mainly from marine organisms on acetylcholinesterase and oxidative stress was evaluated by a chemical-based method in vitro and cell assay model. The results show that all-trans astaxanthin was a reversible competitive inhibitor and exhibited a strong inhibition effect with half inhibitory concentration (IC50 value) of 8.64 µmol/L. Furthermore, all-trans astaxanthin inhibited oxidative stress through reducing malondialdehyde content and increasing the activity of superoxide dismutase as well as catalase. All-trans astaxanthin could induce the changes of the secondary structure to reduce acetylcholinesterase activity. Molecular-docking analysis reveals that all-trans astaxanthin prevented substrate from binding to acetylcholinesterase by occupying the space of the active pocket to cause the inhibition. Our finding suggests that all-trans astaxanthin might be a nutraceutical supplement for Alzheimer´s disease prevention.


Assuntos
Acetilcolinesterase , Doença de Alzheimer , Doença de Alzheimer/tratamento farmacológico , Antioxidantes/química , Antioxidantes/farmacologia , Humanos , Estresse Oxidativo , Xantofilas/farmacologia
18.
Water Sci Technol ; 85(3): 827-838, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35166703

RESUMO

Black and odorous water bodies are an extreme phenomenon that impair ecological integrity, adversely affect the lives of residents and the town's image, and cause unpleasant sensory experiences. Herein, we consider a black and smelly river in Heshan City, Guangdong Province, as a case study. The proposed comprehensive governance process combines the use of pollution control and interception, sediment remediation, aeration oxygenation, a high-efficiency biological contact oxidation/denitrification pond, and ecosystem construction. The project operation results showed that the combined process can effectively improve water quality. The water quality of the river improved to the Class V standard. All indicators met the requirements of the 'China Surface Water Environmental Quality Standard' (GB3838-2002). River water quality indicators, monitored for four months, revealed that water transparency and dissolved oxygen increased by 5.9 times and 24.5 times, respectively. Dichromate index (CODcr), total phosphorus (TP), and ammonia nitrogen (NH3-N) were reduced by 5.8, 4.17, and 5.17 times when compared to the values observed before treatment. The black-odor and eutrophication of the river were successfully eliminated, and the water quality improved significantly. In general, the combined process exhibits a high technical feasibility for implementation, providing a specific reference value for the treatment of black and odorous water bodies in urban settings.


Assuntos
Ecossistema , Poluentes Químicos da Água , China , Monitoramento Ambiental , Nitrogênio/análise , Odorantes , Fósforo/análise , Rios , Poluentes Químicos da Água/análise , Qualidade da Água
19.
Gigascience ; 122022 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-37039117

RESUMO

BACKGROUND: Leeches have been used in traditional Chinese medicine since prehistoric times to treat a spectrum of ailments, but very little is known about their physiological, genetic, and evolutionary characteristics. FINDINGS: We sequenced and assembled chromosome-level genomes of 3 leech species (bloodsucking Hirudo nipponia and Hirudinaria manillensis and nonbloodsucking Whitmania pigra). The dynamic population histories and genome-wide expression patterns of the 2 bloodsucking leech species were found to be similar. A combined analysis of the genomic and transcriptional data revealed that the bloodsucking leeches have a presumably enhanced auditory sense for prey location in relatively deep fresh water. The copy number of genes related to anticoagulation, analgesia, and anti-inflammation increased in the bloodsucking leeches, and their gene expressions responded dynamically to the bloodsucking process. Furthermore, the expanded FBN1 gene family may help in rapid body swelling of leeches after bloodsucking, and the expanded GLB3 gene family may be associated with long-term storage of prey blood in a leech's body. CONCLUSIONS: The high-quality reference genomes and comprehensive datasets obtained in this study may facilitate innovations in the artificial culture and strain optimization of leeches.


Assuntos
Genoma , Sanguessugas , Animais , Sequência de Bases , Sanguessugas/genética , Evolução Biológica
20.
Membranes (Basel) ; 11(11)2021 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-34832103

RESUMO

The nutrient removal and biomass production of the internal circulating fluidized bed microalgae membrane bioreactor (ICFB-MMBR) was studied under different cultivation modes, influent TOC, influent pH, and influent N/P. Platymonas helgolandica tsingtaoensis was used as the biological source. The growth of P. helgolandica tsingtaoensis and the removal efficiency of pollutants in the mixotrophy culture mode were improved compared with other culture modes. With the increased influent TOC, the average growth rate of P. helgolandica tsingtaoensis increased, and ammonia nitrogen and total phosphorus removal rate were improved. The P. helgolandica tsingtaoensis growth rate and nutrient removal efficiencies at the influent pH of 8 were the best among the different influent pH values. As the influent N/P ratio increased from 5 to 20, the P. helgolandica tsingtaoensis growth rate and pollutant removal rate increased gradually. When the influent N/P ratio was higher than 20, the P. helgolandica tsingtaoensis growth rate and pollutant removal rate tended to be stable and did not significantly change with the increase of influent N/P ratio. At the proper influent conditions, the high P. helgolandica tsingtaoensis biomass and nutrient removal efficiency could be obtained in the microalgae membrane bioreactor, which could provide a theoretical basis for the application of the system for wastewater treatment.

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