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1.
Acta Pharm Sin B ; 14(4): 1726-1741, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38572107

RESUMO

Pulmonary hypertension (PH) is a fatal disorder characterized by pulmonary vascular remodeling and obstruction. The phosphodiesterase 4 (PDE4) family hydrolyzes cyclic AMP (cAMP) and is comprised of four subtypes (PDE4A-D). Previous studies have shown the beneficial effects of pan-PDE4 inhibitors in rodent PH; however, this class of drugs is associated with side effects owing to the broad inhibition of all four PDE4 isozymes. Here, we demonstrate that PDE4B is the predominant PDE isozyme in lungs and that it was upregulated in rodent and human PH lung tissues. We also confirmed that PDE4B is mainly expressed in the lung endothelial cells (ECs). Evaluation of PH in Pde4b wild type and knockout mice confirmed that Pde4b is important for the vascular remodeling associated with PH. In vivo EC lineage tracing demonstrated that Pde4b induces PH development by driving endothelial-to-mesenchymal transition (EndMT), and mechanistic studies showed that Pde4b regulates EndMT by antagonizing the cAMP-dependent PKA-CREB-BMPRII axis. Finally, treating PH rats with a PDE4B-specific inhibitor validated that PDE4B inhibition has a significant pharmacological effect in the alleviation of PH. Collectively, our findings indicate a critical role for PDE4B in EndMT and PH, prompting further studies of PDE4B-specific inhibitors as a therapeutic strategy for PH.

2.
Antonie Van Leeuwenhoek ; 117(1): 73, 2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38676821

RESUMO

The deoxynivalenol (DON)-degrading bacterium JB1-3-2 T was isolated from a rhizosphere soil sample of cucumber collected from a greenhouse located in Zhenjiang, Eastern China. The JB1-3-2 T strain is a Gram-stain-positive, nonmotile and round actinomycete. Growth was observed at temperatures between 15 and 40 ℃ (optimum, 35 ℃), in the presence of 15% (w/v) NaCl (optimum, 3%), and at pH 3 and 11 (optimum, 7). The major cellular fatty acids identified were anteiso-C15:0, iso-C16:0 and anteiso-C17:0. Genome sequencing revealed a genome size of 4.11 Mb and a DNA G + C content of 72.5 mol%. Phylogenetic analysis based on 16S rRNA gene sequences indicated that the JB1-3-2 T strain was most closely related to type strains of the Oerskovia species, with the highest sequence similarity to Oerskovia turbata NRRL B-8019 T (98.2%), and shared 98.1% sequence identity with other valid type strains of this genus. Digital DNA‒DNA hybridization (dDDH) and average nucleotide identity (ANI) showed 21.8-22.2% and 77.2-77.3% relatedness, respectively, between JB1-3-2 T and type strains of the genus Oerskovia. Based on genotypic, phylogenetic, chemotaxonomic, physiological and biochemical characterization, Oerskovia flava, a novel species in the genus Oerskovia, was proposed, and the type strain was JB1-3-2 T (= CGMCC 1.18555 T = JCM 35248 T). Additionally, this novel strain has a DON degradation ability that other species in the genus Oerskovia do not possess, and glutathione-S-transferase was speculated to be the key enzyme for strain JB1-3-2 T to degrade DON.


Assuntos
Cucumis sativus , Ácidos Graxos , Filogenia , RNA Ribossômico 16S , Rizosfera , Microbiologia do Solo , Tricotecenos , Cucumis sativus/microbiologia , Tricotecenos/metabolismo , RNA Ribossômico 16S/genética , Ácidos Graxos/metabolismo , DNA Bacteriano/genética , China , Composição de Bases , Técnicas de Tipagem Bacteriana , Análise de Sequência de DNA , Genoma Bacteriano
3.
Circulation ; 149(17): 1354-1371, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38314588

RESUMO

BACKGROUND: Pulmonary hypertension (PH) is a progressive cardiopulmonary disease with a high mortality rate. Although growing evidence has revealed the importance of dysregulated energetic metabolism in the pathogenesis of PH, the underlying cellular and molecular mechanisms are not fully understood. In this study, we focused on ME1 (malic enzyme 1), a key enzyme linking glycolysis to the tricarboxylic acid cycle. We aimed to determine the role and mechanistic action of ME1 in PH. METHODS: Global and endothelial-specific ME1 knockout mice were used to investigate the role of ME1 in hypoxia- and SU5416/hypoxia (SuHx)-induced PH. Small hairpin RNA and ME1 enzymatic inhibitor (ME1*) were used to study the mechanism of ME1 in pulmonary artery endothelial cells. Downstream key metabolic pathways and mediators of ME1 were identified by metabolomics analysis in vivo and ME1-mediated energetic alterations were examined by Seahorse metabolic analysis in vitro. The pharmacological effect of ME1* on PH treatment was evaluated in PH animal models induced by SuHx. RESULTS: We found that ME1 protein level and enzymatic activity were highly elevated in lung tissues of patients and mice with PH, primarily in vascular endothelial cells. Global knockout of ME1 protected mice from developing hypoxia- or SuHx-induced PH. Endothelial-specific ME1 deletion similarly attenuated pulmonary vascular remodeling and PH development in mice, suggesting a critical role of endothelial ME1 in PH. Mechanistic studies revealed that ME1 inhibition promoted downstream adenosine production and activated A2AR-mediated adenosine signaling, which leads to an increase in nitric oxide generation and a decrease in proinflammatory molecule expression in endothelial cells. ME1 inhibition activated adenosine production in an ATP-dependent manner through regulating malate-aspartate NADH (nicotinamide adenine dinucleotide plus hydrogen) shuttle and thereby balancing oxidative phosphorylation and glycolysis. Pharmacological inactivation of ME1 attenuated the progression of PH in both preventive and therapeutic settings by promoting adenosine production in vivo. CONCLUSIONS: Our findings indicate that ME1 upregulation in endothelial cells plays a causative role in PH development by negatively regulating adenosine production and subsequently dysregulating endothelial functions. Our findings also suggest that ME1 may represent as a novel pharmacological target for upregulating protective adenosine signaling in PH therapy.

4.
Antonie Van Leeuwenhoek ; 117(1): 14, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38170333

RESUMO

A Gram-stain-positive, rod-shaped, non-spore-forming, alkane degrading bacterium, designated DJM-14T, was isolated from oilfield alkali-saline soil in Heilongjiang, Northeast China. On the basis of 16 S rRNA gene sequencing, strain DJM-14T was shown to belong to the genus Nocardioides, and related most closely to Nocardioides terrigena KCTC 19,217T (95.53% 16 S rRNA gene sequence similarity). Strain DJM-14T was observed to grow at 25-35 °C, pH 7.0-11.0, in the presence of 0-6.0% (w/v) NaCl. The predominant respiratory quinone was MK-8 (H4) and LL-diaminopimelic acid was the diagnostic diamino acid in the cell-wall peptidoglycan. The major fatty acids were identified as iso-C16:0 and C18:1 ω9c. It contained diphosphatidylglycerol, phosphatidylglycerol and phosphatidylinositol as the polar lipids. The genome (3,722,608 bp), composed of 24 contigs, had a G + C content of 69.6 mol%. Out of the 3667 predicted genes, 3618 were protein-coding genes, and 49 were ncRNAs. Digital DNA-DNA hybridization (dDDH) estimation and average nucleotide identity (ANI) of strain DJM-14T against genomes of the type strains of related species in the same family ranged between 18.7% and 20.0%; 68.8% and 73.6%, respectively. According to phenotypic, genotypic and phylogenetic data, strain DJM-14T represents a novel species in the genus Nocardioides, for which the name Nocardioides limicola sp. nov. is proposed and the type strain is DJM-14T (= CGMCC 4.7593T, =JCM 33,692T). In addition, novel strains were able to grow with n-alkane (C24-C36) as the sole carbon source. Multiple copies of alkane 1-monooxygenase (alkB) gene, as well as alcohol dehydrogenase gene and aldehyde dehydrogenase gene involved in the alkane assimilation were annotated in the genome of type strain DJM-14T.


Assuntos
Nocardioides , Fosfolipídeos , Fosfolipídeos/química , Nocardioides/genética , Solo , Filogenia , Campos de Petróleo e Gás , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Ácidos Graxos/química , DNA , DNA Bacteriano/genética , Técnicas de Tipagem Bacteriana
5.
Oncol Lett ; 27(2): 74, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38192672

RESUMO

Collision tumors consisting of hepatocellular carcinoma (HCC) and cavernous hemangioma (CH) are rare and the clinicopathological characteristics or cause of the tumors remain unclear. The present study reports the case of a 71-year-old male patient who was admitted to Sunshine Union Hospital (Weifang, China) due to a liver mass found during a routine physical examination. computed tomography scans showed a main lesion of ~4.0×4.2×3.5 cm in segment IV of the patient's liver and a nodule of ~2.4×2.2×1.3 cm in the lower-left part of the lesion, which was clearly demarcated from the main lesion. The capsule of the lesion was found to be intact during the operation performed to remove the tumor. The final patient diagnosis was of a HCC-CH collision tumor based on pathology. The patient underwent follow-up for 6 months after surgery and no recurrence was observed.

6.
BMC Genomics ; 25(1): 123, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38287293

RESUMO

BACKGROUND: Haloxylon ammodendron holds significance as an ecological plant, showcasing remarkable adaptability to desert conditions, halophytic environments, and sand fixation. With its potential for carbon sequestration, it emerges as a promising candidate for environmental sustainability. Furthermore, it serves as a valuable C4 plant model, offering insights into the genetic foundations of extreme drought tolerance. Despite the availability of plastid and nuclear genomes, the absence of a mitochondrial genome (mitogenome or mtDNA) hinders a comprehensive understanding of its its mtDNA structure, organization, and phylogenetic implications. RESULTS: In the present study, the mitochondrial genome of H. ammodendron was assembled and annotated, resulting in a multi-chromosomal configuration with two circular chromosomes. The mtDNA measured 210,149 bp in length and contained 31 protein-coding genes, 18 tRNA and three rRNA. Our analysis identified a total of 66 simple sequence repeats along with 27 tandem repeats, 312 forward repeats, and 303 palindromic repeats were found. Notably, 17 sequence fragments displayed homology between the mtDNA and chloroplast genome (cpDNA), spanning 5233 bp, accounting for 2.49% of the total mitogenome size. Additionally, we predicted 337 RNA editing sites, all of the C-to-U conversion type. Phylogenetic inference confidently placed H. ammodendron in the Amaranthacea family and its close relative, Suaeda glacum. CONCLUSIONS: H. ammodendron mtDNA showed a multi-chromosomal structure with two fully circularized molecules. This newly characterized mtDNA represents a valuable resource for gaining insights into the basis of mtDNA structure variation within Caryophyllales and the evolution of land plants, contributing to their identification, and classification.


Assuntos
Chenopodiaceae , Genoma Mitocondrial , Plantas Tolerantes a Sal/genética , Filogenia , Chenopodiaceae/genética , DNA Mitocondrial/genética
7.
J Sci Food Agric ; 104(6): 3265-3274, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38087399

RESUMO

BACKGROUND: Qizha Shuangye granules (QSG) comprise six traditional Chinese herbal medicines (TCHMs), which have a long history of treating hyperlipidemia (HLP) in China. This study aimed to evaluate the potential lipid-lowering effects of QSG in an HLP rat model and investigate possible mechanisms. The HLP rat model was induced by a high-fat diet. Lipid-related indicators in serum were detected. Serum and liver metabolites were investigated using a liquid chromatography-mass spectrometry-based metabolomics approach. A herb-compound-target-metabolite (H-C-T-M) network was further constructed to reveal the possible molecular mechanism of QSG to alleviate HLP. RESULTS: The administration of QSG inhibited the HLP-induced changes in total cholesterol, triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and non-esterified fatty acid (NEFA) levels. Additionally, QSG significantly attenuated the liver histopathological changes induced by HLP. Metabolomic analysis showed the serum and liver metabolic disorders presented in HLP rats. QSG can reverse the abnormal metabolism caused by HLP. Through network pharmacology analysis, key proteins such as androgen receptor, 3-hydroxy-3-methylglutaryl-CoA reductase, and peroxisome proliferator-activated receptor-α were screened out, and they were speculated to be possible therapeutic targets for QSG to treat HLP. CONCLUSION: The present study integrated metabolomics and network pharmacology analysis to reveal the efficacy and possible mechanism of QSG in treating HLP, which provides a new reference for the research and development of QSG as a functional food. © 2023 Society of Chemical Industry.


Assuntos
Medicamentos de Ervas Chinesas , Hiperlipidemias , Ratos , Animais , Farmacologia em Rede , Metabolômica , Hiperlipidemias/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Triglicerídeos , Colesterol
8.
J Ethnopharmacol ; 322: 117650, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38135230

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Shegan Mahuang Decoction (SMD) is a classic traditional Chinese medicine (TCM) formula for asthma treatment, but the anti-asthma mechanism of SMD is still not fully studied. AIMS OF THE STUDY: In this study, we established an ovalbumin (OVA)-induced asthma rat model and treated it with SMD to observe its anti-asthma effect and explore the related mechanism. MATERIALS AND METHODS: We evaluated the anti-inflammatory effect of SMD via testing the levels of immunoglobulin E (IgE), C-reactive protein (CRP), interleukin-4 (IL-4), interleukin-6 (IL-6) in serum and performing the hematoxylin-eosin (H&E) staining of lung tissue slices. We analyzed the variations of metabolites and proteins in the lung tissue of different groups using liquid chromatography-mass spectrometry (LC-MS)-based untargeted metabolomics and TMT-based proteomics approaches. The metabolic biomarkers and differentially expressed proteins (DEPs) were picked, and the related signal transduction pathways were also investigated. In addition, the key proteins on the signaling pathway were validated through western blotting (WB) experiment to reveal the anti-asthma mechanism of SMD. RESULTS: The results showed that the SMD could significantly reduce the serum levels of IgE, CRP, IL-4, and IL-6 and attenuate the OVA-induced pathological changes in lung tissue. A total of 34 metabolic biomarkers and 84 DEPs were screened from rat lung tissue, which were mainly associated with lipid metabolism, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation, the excessive production of reactive oxygen species (ROS), and lysosome pathway. Besides, SMD could inhibit the myeloid differentiation factor 88 (MyD88)/inhibitor of kappa B kinase (IKK)/nuclear factor-kappa B (NF-κB) signaling pathway to exhibit anti-inflammatory activities. CONCLUSIONS: SMD exhibited a therapeutic effect on asthma, which possibly be exerted by inhibiting the MyD88/IKK/NF-κB signaling pathway.


Assuntos
Antiasmáticos , Asma , Medicamentos de Ervas Chinesas , Ratos , Animais , Proteoma , Interleucina-4/metabolismo , NF-kappa B/metabolismo , Interleucina-6/metabolismo , Fator 88 de Diferenciação Mieloide/metabolismo , Multiômica , Asma/induzido quimicamente , Asma/tratamento farmacológico , Asma/metabolismo , Pulmão , Antiasmáticos/farmacologia , Antiasmáticos/uso terapêutico , Anti-Inflamatórios/farmacologia , Metaboloma , Biomarcadores/metabolismo , Imunoglobulina E , Ovalbumina/farmacologia
9.
Sci Adv ; 9(48): eadh1891, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-38039374

RESUMO

Cancer stem cells (CSCs) drive tumor growth, metastasis, and chemoresistance. While emerging evidence suggests that CSCs have a unique dependency on lipid metabolism, the functions and regulation of distinct lipid species in CSCs remain poorly understood. Here, we developed a stem cell factor SOX9-based reporter for isolating CSCs in primary tumors and metastases of spontaneous mammary tumor models. Transcriptomic analyses uncover that SOX9high CSCs up-regulate the ABCA12 lipid transporter. ABCA12 down-regulation impairs cancer stemness and chemoresistance. Lipidomic analyses reveal that ABCA12 maintains cancer stemness and chemoresistance by reducing intracellular ceramide abundance, identifying a CSC-associated function of ABCA subfamily transporter. Ceramide suppresses cancer stemness by inhibiting the YAP-SOX9 signaling pathway in CSCs. Increasing ceramide levels in tumors enhances their sensitivity to chemotherapy and prevents the enrichment of SOX9high CSCs. In addition, SOX9high and ABCA12high cancer cells contribute to chemoresistance in human patient-derived xenografts. These findings identify a CSC-suppressing lipid metabolism pathway that can be exploited to inhibit CSCs and overcome chemoresistance.


Assuntos
Neoplasias da Mama , Resistencia a Medicamentos Antineoplásicos , Humanos , Feminino , Linhagem Celular Tumoral , Neoplasias da Mama/metabolismo , Homeostase , Células-Tronco Neoplásicas/metabolismo , Lipídeos , Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo
10.
J Sep Sci ; 46(24): e2300531, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37933967

RESUMO

Our previous studies confirmed the efficacy of gross saponins of Tribulus terrestris L. fruit in treating cerebral ischemia. This study aimed to investigate the related mechanisms in vitro. The lipopolysaccharide-induced BV2 cells model was constructed and treated with gross saponins at different concentrations to explore its anti-inflammatory activity. The cell metabolite changes were tracked by liquid chromatography-mass spectrometry (LC-MS)-based metabolomics, and the metabolic biomarkers and related metabolic pathways were analyzed. Molecular biochemistry analysis was further used to verify the relevant inflammatory pathways. The results showed that the saponins reduced nitric oxide release and the secretion of tumor necrosis factor-alpha, interleukin-1ß, and interleukin-6 from lipopolysaccharide-induced BV2 cells. Metabolic perturbations occurred in lipopolysaccharide-treated BV2 cells, which could be reversed by drug treatment via mainly regulating glycerophospholipid metabolism, tryptophan metabolism, purine metabolism pathways, etc. The western blot analysis demonstrated that saponin could suppress the activation of the inflammatory-related signaling pathway. The present study explored the in vitro anti-inflammatory mechanism of gross saponins of Tribulus terrestris L. fruit using an LC-MS-based cell metabolomics approach, which confirms the great potential of LC-MS for drug efficacy evaluation and can be applied in other herbal medicine-related analyses.


Assuntos
Saponinas , Tribulus , Saponinas/análise , Frutas/química , Espectrometria de Massa com Cromatografia Líquida , Tribulus/química , Lipopolissacarídeos/farmacologia , Metabolômica , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/análise
11.
Dev Cell ; 58(23): 2700-2717.e12, 2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-37963469

RESUMO

How dedifferentiated stem-like tumor cells evade immunosurveillance remains poorly understood. We show that the lineage-plasticity regulator SOX9, which is upregulated in dedifferentiated tumor cells, limits the number of infiltrating T lymphocytes in premalignant lesions of mouse basal-like breast cancer. SOX9-mediated immunosuppression is required for the progression of in situ tumors to invasive carcinoma. SOX9 induces the expression of immune checkpoint B7x/B7-H4 through STAT3 activation and direct transcriptional regulation. B7x is upregulated in dedifferentiated tumor cells and protects them from immunosurveillance. B7x also protects mammary gland regeneration in immunocompetent mice. In advanced tumors, B7x targeting inhibits tumor growth and overcomes resistance to anti-PD-L1 immunotherapy. In human breast cancer, SOX9 and B7x expression are correlated and associated with reduced CD8+ T cell infiltration. This study, using mouse models, cell lines, and patient samples, identifies a dedifferentiation-associated immunosuppression mechanism and demonstrates the therapeutic potential of targeting the SOX9-B7x pathway in basal-like breast cancer.


Assuntos
Neoplasias da Mama , Animais , Feminino , Humanos , Camundongos , Linfócitos T CD8-Positivos , Terapia de Imunossupressão , Fatores de Transcrição SOX9 , Inibidor 1 da Ativação de Células T com Domínio V-Set/metabolismo
12.
Med Int (Lond) ; 3(6): 59, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37954522

RESUMO

The present study aimed to investigate the expression of ubiquitin-conjugating enzyme E2 variant 1 (Ube2v1) in colorectal cancer (CRC) and its clinical significance. The differential expression of Ube2v1 in CRC tissues and normal intestinal tissues, as well as the association between Ube2v1 expression and the prognosis of patients with CRC were analyzed using bioinformatics analyses. TIMER database analysis revealed higher Ube2v1 expression in CRC tissues than in normal intestinal tissues. Cancerous and normal tissues collected retrospectively from 37 cases of CRC between July, 2022 and June, 2023 were analyzed for Ube2v1 expression using immunohistochemistry, and the associations between Ube2v1 expression and the clinical pathological features of patients with CRC were analyzed. Ube2v1 expression was associated with lymph node metastasis in patients with CRC (P<0.05). However, bioinformatics analysis using the GEPIA2 and HPA database revealed that Ube2v1 was not associated with the overall survival of patients with CRC. On the whole, the present study demonstrates that due to its high expression and association with lymph node metastasis, Ube2v1 may serve as a potential target for the treatment of CRC.

13.
Neuron ; 111(20): 3135-3137, 2023 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-37857087

RESUMO

In this issue of Neuron, Zheng et al.1 report the monomeric architecture of mechanosensitive ion channels TMEM63A and TMEM63B. They show that these high-threshold channels function as monomers on the plasma membrane.


Assuntos
Canais Iônicos , Mecanotransdução Celular , Canais Iônicos/metabolismo , Membrana Celular/metabolismo , Mecanotransdução Celular/fisiologia , Neurônios/metabolismo
14.
Exp Ther Med ; 26(5): 539, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37869649

RESUMO

Under normal circumstances, gastric mucosa only exists within the stomach. However, in certain situations, gastric mucosal tissue may undergo ectopia, commonly occurring in the esophagus and intestine, with rare occurrences within the stomach itself. A comprehensive literature review was performed to understand the distinct characteristics of ectopic gastric mucosa (EGM) in the stomach and investigate a rare incident of this disease, providing an in-depth analysis of the clinical, histopathologic, and differential diagnostic findings. The case was a 47-year-old man with acid reflux, heartburn, abdominal distension, and diarrhea (5-10 times daily) for >10 years. A gastroscope indicated a submucosal protuberance lesion in the gastric body that felt hard with biopsy forceps. A well-defined nodule under the mucosal muscle was revealed microscopically, composed of epithelial elements and no atypia. Immunohistochemical staining demonstrated similar EGM expression patterns compared with normal gastric mucosa. The present case report highlights the importance of accurate EGM diagnosis and understanding.

15.
Ann Med Surg (Lond) ; 85(10): 4947-4953, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37811106

RESUMO

Ultrasound-guided quadratus lumborum block (QLB) has been gradually carried out in clinical practice. However, some clinical evidence is contradictory, and no studies have summarized and described these results. The authors reviewed the anatomical characteristics of QLB and summarized the advantages and disadvantages of four puncture methods, so as to facilitate the clinical application of QLB.

16.
Mol Nutr Food Res ; 67(24): e2300447, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37876150

RESUMO

SCOPE: Among herbal dietary supplements, the extract of Tribulus terrestris L. (TT) has been used as a commercially registered product in multiple studies. The previous studies demonstrate the protective effect of gross saponins of TT (GSTTF) on ischemic stroke. However, the mechanism by which GSTTF protects against ischemic stroke is still unclear. METHODS AND RESULTS: The study applies molecular biology and unbiased transcriptomics to explore the pathways and targets underlying the therapeutic impact of GSTTF in treating ischemic stroke. The mRNA of brain tissues from different groups is analyzed using a transcriptomics method. The data reveal that treatment with GSTTF significantly reduces elevated CRP, IL-6, and Ca2+ levels induced by middle cerebral artery occlusion (MCAO). A total of 61 differentially expressed genes (DEGs) are identified, GSTTF is found to effectively reverse the abnormal mRNA expression levels in rat brain tissues affected by ischemic stroke models. These positive effects of GSTTF are likely achieved through the suppression of calcium ion and the MyD88/IKK/NF-κB signaling pathway. CONCLUSIONS: This study uncovers the mechanisms behind the efficacy of GSTTF in treating ischemic stroke, which not only expands its potential medicinal applications but also confirmed its potential as a dietary supplement.


Assuntos
AVC Isquêmico , Tribulus , Ratos , Animais , Transdução de Sinais , Suplementos Nutricionais , RNA Mensageiro/genética
17.
Cell Rep ; 42(9): 113003, 2023 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-37682707

RESUMO

Oncogenic KRAS mutations are a key driver for initiation and progression in non-small cell lung cancer (NSCLC). However, how post-translational modifications (PTMs) of KRAS, especially methylation, modify KRAS activity remain largely unclear. Here, we show that SET domain containing histone lysine methyltransferase 7 (SETD7) interacts with KRAS and methylates KRAS at lysines 182 and 184. SETD7-mediated methylation of KRAS leads to degradation of KRAS and attenuation of the RAS/MEK/ERK signaling cascade, endowing SETD7 with a potent tumor-suppressive role in NSCLC, both in vitro and in vivo. Mechanistically, RABGEF1, a ubiquitin E3 ligase of KRAS, is recruited and promotes KRAS degradation in a K182/K184 methylation-dependent manner. Notably, SETD7 is inversely correlated with KRAS at the protein level in clinical NSCLC tissues. Low SETD7 or RABGEF1 expression is associated with poor prognosis in lung adenocarcinoma patients. Altogether, our results define a tumor-suppressive function of SETD7 that operates via modulating KRAS methylation and degradation.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Neoplasias Pulmonares/patologia , Metilação , Histona-Lisina N-Metiltransferase/genética , Histona-Lisina N-Metiltransferase/metabolismo , Processamento de Proteína Pós-Traducional , Fatores de Troca do Nucleotídeo Guanina/metabolismo
18.
Oncol Lett ; 26(2): 341, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37427343

RESUMO

The present study describes a rare case of glioblastoma with a primitive neuronal component (GBM-PNC), and provides an in-depth analysis of the clinical, pathological and differential diagnostic findings. A comprehensive literature review was conducted to enhance the understanding of GBM-PNC, revealing its distinct characteristics and prognostic implications. A 57-year-old woman presented with acute onset headache, nausea and vomiting, leading to the identification of an intracranial mass through magnetic resonance imaging. Surgical resection revealed the coexistence of a glial component and a PNC within the tumor. Immunohistochemical analysis detected the expression of glial fibrillary acidic protein in the glial component and synaptin in the PNC. The pathological diagnosis confirmed the presence of GBM-PNC. Gene detection analysis revealed no mutations in isocitrate dehydrogenase (IDH)1 and IDH2, and neurotrophic tyrosine kinase receptor-1 (NTRK1), NTRK2 and NTRK3 genes. GBM-PNC is characterized by a propensity for recurrence and metastasis, with a low 5-year survival rate. The present case report highlights the importance of accurate diagnosis and comprehensive characterization of GBM-PNC to guide treatment decisions and improve patient outcomes.

19.
Foods ; 12(13)2023 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-37444288

RESUMO

The hazard of nitrite caused by microorganisms is the main food safety problem in the pickle production. To seek a method to control the nitrite hazards of pickles by regulating microbial community without additional substances, we focused on cold plasma because Gram-negative and Gram-positive bacteria have different degrees of sensitivity to the sterilization of cold plasma. Using radish pickles as the experimental object, based on colony counting, dynamic monitoring of pH and nitrite, qPCR and high-throughput sequencing, it was found that when the raw material was treated with dielectric barrier discharge (DBD) cold plasma at 40 kV for 60 s, Gram-negative bacteria with the potential to produce nitrite were preferentially sterilized. Meanwhile, Gram-positive bacteria dominated by the lactic acid bacteria were retained to accelerate the acid production rate, initiate the self-degradation of nitrite in advance and significantly reduce the peak value and accumulation of nitrite during the fermentation process of pickled radish. This study preliminarily verified that DBD cold plasma can inhibit the nitrite generation and accelerate the self-degradation of nitrite by regulating the structure and abundance of microbial community in radish pickles, which provides an important reference for the control of nitrite hazards in the fermentation process of pickles without additives.

20.
ACS Biomater Sci Eng ; 9(6): 3335-3347, 2023 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-37144723

RESUMO

Fragrances, which are commonly used in food, textiles, consumer products, and medical supplies, are volatile compounds that require stabilization and controlled release due to their sensitivity to environmental conditions such as light, oxygen, temperature, and humidity. Encapsulation in various material matrices is a desired technique for these purposes, and there is a growing interest in using sustainable natural materials to reduce environmental impact. In this study, fragrance encapsulation in microspheres made from silk fibroin (SF) was investigated. Fragrance-loaded silk fibroin microspheres (Fr-SFMSs) were prepared by adding fragrance/surfactant emulsions to silk solutions, followed by mixing them with polyethylene glycol under ambient conditions. The study investigated eight different fragrances, where citral, beta-ionone, and eugenol showed higher binding affinities to silk than the other five fragrances, resulting in better microsphere formation with uniform sizes and higher fragrance loading (10-30%). Citral-SFMSs showed characteristic crystalline ß-sheet structures of SF, high thermal stability (initial weight loss at 255 °C), long shelf life at 37 °C (>60 days), and sustained release (∼30% of citral remained after incubation at 60 °C for 24 h). When citral-SFMSs with different sizes were used to treat cotton fabrics, about 80% of the fragrance remained on the fabrics after one wash, and the duration of release from the treated fabrics was significantly longer than that of control samples treated with citral alone (no microspheres). This method of preparing Fr-SFMSs has potential applications in textile finishing, cosmetics, and the food industry.


Assuntos
Fibroínas , Seda , Seda/química , Odorantes , Preparações de Ação Retardada
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