International Journal of Molecular Sciences最新文献

{"title":"Transcriptomic–Proteomic Analysis Revealed the Regulatory Mechanism of Peanut in Response to Fusarium oxysporum","authors":"Mian Wang, Lifei Zhu, Chushu Zhang, Haixiang Zhou, Yueyi Tang, Shining Cao, Jing Chen, Jiancheng Zhang","doi":"10.3390/ijms25010619","DOIUrl":"https://doi.org/10.3390/ijms25010619","url":null,"abstract":"Peanut Fusarium rot, which is widely observed in the main peanut-producing areas in China, has become a significant factor that has limited the yield and quality in recent years. It is highly urgent and significant to clarify the regulatory mechanism of peanuts in response to Fusarium oxysporum. In this study, transcriptome and proteome profiling were combined to provide new insights into the molecular mechanisms of peanut stems after F. oxysporums infection. A total of 3746 differentially expressed genes (DEGs) and 305 differentially expressed proteins (DEPs) were screened. The upregulated DEGs and DEPs were primarily enriched in flavonoid biosynthesis, circadian rhythm-plant, and plant–pathogen interaction pathways. Then, qRT-PCR analysis revealed that the expression levels of phenylalanine ammonia-lyase (PAL), chalcone isomerase (CHI), and cinnamic acid-4-hydroxylase (C4H) genes increased after F. oxysporums infection. Moreover, the expressions of these genes varied in different peanut tissues. All the results revealed that many metabolic pathways in peanut were activated by improving key gene expressions and the contents of key enzymes, which play critical roles in preventing fungi infection. Importantly, this research provides the foundation of biological and chemical analysis for peanut disease resistance mechanisms.","PeriodicalId":509625,"journal":{"name":"International Journal of Molecular Sciences","volume":"3 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139388527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endogenous Signaling Molecule Activating (ESMA) CARs: A Novel CAR Design Showing a Favorable Risk to Potency Ratio for the Treatment of Triple Negative Breast Cancer","authors":"Mira Ebbinghaus, Katharina Wittich, Benjamin Bancher, Valeriia Lebedeva, Anijutta Appelshoffer, Julia Femel, Martin S. Helm, J. Kollet, Olaf Hardt, Rita Pfeifer","doi":"10.3390/ijms25010615","DOIUrl":"https://doi.org/10.3390/ijms25010615","url":null,"abstract":"As chimeric antigen receptor (CAR) T cell therapy continues to gain attention as a valuable treatment option against different cancers, strategies to improve its potency and decrease the side effects associated with this therapy have become increasingly relevant. Herein, we report an alternative CAR design that incorporates transmembrane domains with the ability to recruit endogenous signaling molecules, eliminating the need for stimulatory signals within the CAR structure. These endogenous signaling molecule activating (ESMA) CARs triggered robust cytotoxic activity and proliferation of the T cells when directed against the triple-negative breast cancer (TNBC) cell line MDA-MB-231 while exhibiting reduced cytokine secretion and exhaustion marker expression compared to their cognate standard second generation CARs. In a NOD SCID Gamma (NSG) MDA-MB-231 xenograft mouse model, the lead candidate maintained longitudinal therapeutic efficacy and an enhanced T cell memory phenotype. Profound tumor infiltration by activated T cells repressed tumor growth, further manifesting the proliferative capacity of the ESMA CAR T cell therapy. Consequently, ESMA CAR T cells entail promising features for improved clinical outcome as a solid tumor treatment option.","PeriodicalId":509625,"journal":{"name":"International Journal of Molecular Sciences","volume":"20 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139388515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Attenuation of PI3K-Akt-mTOR Pathway to Reduce Cancer Stemness on Chemoresistant Lung Cancer Cells by Shikonin and Synergy with BEZ235 Inhibitor","authors":"Yen-Hsiang Huang, Ling-Yen Chiu, Jeng-Sen Tseng, Kuo-Hsuan Hsu, Chang-Han Chen, G. Sheu, Tsung-Ying Yang","doi":"10.3390/ijms25010616","DOIUrl":"https://doi.org/10.3390/ijms25010616","url":null,"abstract":"Lung cancer is considered the number one cause of cancer-related deaths worldwide. Although current treatments initially reduce the lung cancer burden, relapse occurs in most cases; the major causes of mortality are drug resistance and cancer stemness. Recent investigations have provided evidence that shikonin generates various bioactivities related to the treatment of cancer. We used shikonin to treat multi-resistant non-small lung cancer cells (DOC-resistant A549/D16, VCR-resistant A549/V16 cells) and defined the anti-cancer efficacy of shikonin. Our results showed shikonin induces apoptosis in these ABCB1-dependent and independent chemoresistance cancer sublines. Furthermore, we found that low doses of shikonin inhibit the proliferation of lung cancer stem-like cells by inhibiting spheroid formation. Concomitantly, the mRNA level and protein of stemness genes (Nanog and Oct4) were repressed significantly on both sublines. Shikonin reduces the phosphorylated Akt and p70s6k levels, indicating that the PI3K/Akt/mTOR signaling pathway is downregulated by shikonin. We further applied several signaling pathway inhibitors that have been used in anti-cancer clinical trials to test whether shikonin is suitable as a sensitizer for various signaling pathway inhibitors. In these experiments, we found that low doses shikonin and dual PI3K-mTOR inhibitor (BEZ235) have a synergistic effect that inhibits the spheroid formation from chemoresistant lung cancer sublines. Inhibiting the proliferation of lung cancer stem cells is believed to reduce the recurrence of lung cancer; therefore, shikonin’s anti-drug resistance and anti-cancer stem cell activities make it a highly interesting molecule for future combined lung cancer therapy.","PeriodicalId":509625,"journal":{"name":"International Journal of Molecular Sciences","volume":"61 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139388429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biodegradation of Typical Plastics: From Microbial Diversity to Metabolic Mechanisms","authors":"Shiwei Lv, Yufei Li, Sufang Zhao, Zongze Shao","doi":"10.3390/ijms25010593","DOIUrl":"https://doi.org/10.3390/ijms25010593","url":null,"abstract":"Plastic production has increased dramatically, leading to accumulated plastic waste in the ocean. Marine plastics can be broken down into microplastics (<5 mm) by sunlight, machinery, and pressure. The accumulation of microplastics in organisms and the release of plastic additives can adversely affect the health of marine organisms. Biodegradation is one way to address plastic pollution in an environmentally friendly manner. Marine microorganisms can be more adapted to fluctuating environmental conditions such as salinity, temperature, pH, and pressure compared with terrestrial microorganisms, providing new opportunities to address plastic pollution. Pseudomonadota (Proteobacteria), Bacteroidota (Bacteroidetes), Bacillota (Firmicutes), and Cyanobacteria were frequently found on plastic biofilms and may degrade plastics. Currently, diverse plastic-degrading bacteria are being isolated from marine environments such as offshore and deep oceanic waters, especially Pseudomonas spp. Bacillus spp. Alcanivoras spp. and Actinomycetes. Some marine fungi and algae have also been revealed as plastic degraders. In this review, we focused on the advances in plastic biodegradation by marine microorganisms and their enzymes (esterase, cutinase, laccase, etc.) involved in the process of biodegradation of polyethylene terephthalate (PET), polystyrene (PS), polyethylene (PE), polyvinyl chloride (PVC), and polypropylene (PP) and highlighted the need to study plastic biodegradation in the deep sea.","PeriodicalId":509625,"journal":{"name":"International Journal of Molecular Sciences","volume":"1 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139390671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"QTL Detection and Candidate Gene Identification for Eating and Cooking Quality Traits in Rice (Oryza sativa L.) via a Genome-Wide Association Study","authors":"Jian-hua Jiang, Shaojie Song, Changmin Hu, Chunyu Jing, Qing Xu, Xinru Li, Mengyuan Zhang, Mei Hai, Jiaming Shen, Ying Zhang, Dezheng Wang, X. Dang","doi":"10.3390/ijms25010630","DOIUrl":"https://doi.org/10.3390/ijms25010630","url":null,"abstract":"The eating and cooking quality (ECQ) directly affects the taste of rice, being closely related to factors such as gelatinization temperature (GT), gel consistency (GC) and amylose content (AC). Mining the quantitative trait loci (QTLs), and gene loci controlling ECQ-related traits is vital. A genome-wide association study on ECQ-related traits was conducted, combining 1.2 million single nucleotide polymorphisms (SNPs) with the phenotypic data of 173 rice accessions. Two QTLs for GT, one for GC and five for AC were identified, of which two were found in previously reported genes, and six were newly found. There were 28 positional candidate genes in the region of qAC11. Based on a linkage disequilibrium (LD) analysis, three candidate genes were screened within the LD region associated with AC. There were significant differences between the haplotypes of LOC_Os11g10170, but no significant differences were found for the other two genes. The qRT-PCR results showed that the gene expression levels in the accessions with high ACs were significantly larger than those in the accessions with low ACs at 35d and 42d after flowering. Hap 2 and Hap 3 of LOC_Os11g10170 reduced the AC by 13.09% and 10.77%, respectively. These results provide a theoretical and material basis for improving the ECQ of rice.","PeriodicalId":509625,"journal":{"name":"International Journal of Molecular Sciences","volume":"3 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139388700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of Cerebrospinal Fluid Extracellular Vesicles by Proximity Extension Assay: A Comparative Study of Four Isolation Kits.","authors":"Sebastian Sjoqvist,&nbsp;Kentaro Otake,&nbsp;Yoshihiko Hirozane","doi":"10.3390/ijms21249425","DOIUrl":"https://doi.org/10.3390/ijms21249425","url":null,"abstract":"<p><p>There is a lack of reliable biomarkers for disorders of the central nervous system (CNS), and diagnostics still heavily rely on symptoms that are both subjective and difficult to quantify. The cerebrospinal fluid (CSF) is a promising source of biomarkers due to its close connection to the CNS. Extracellular vesicles are actively secreted by cells, and proteomic analysis of CSF extracellular vesicles (EVs) and their molecular composition likely reflects changes in the CNS to a higher extent compared with total CSF, especially in the case of neuroinflammation, which could increase blood-brain barrier permeability and cause an influx of plasma proteins into the CSF. We used proximity extension assay for proteomic analysis due to its high sensitivity. We believe that this methodology could be useful for de novo biomarker discovery for several CNS diseases. We compared four commercially available kits for EV isolation: MagCapture and ExoIntact (based on magnetic beads), EVSecond L70 (size-exclusion chromatography), and exoEasy (membrane affinity). The isolated EVs were characterized by nanoparticle tracking analysis, ELISA (CD63, CD81 and albumin), and proximity extension assay (PEA) using two different panels, each consisting of 92 markers. The exoEasy samples did not pass the built-in quality controls and were excluded from downstream analysis. The number of detectable proteins in the ExoIntact samples was considerably higher (~150% for the cardiovascular III panel and ~320% for the cell regulation panel) compared with other groups. ExoIntact also showed the highest intersample correlation with an average Pearson's correlation coefficient of 0.991 compared with 0.985 and 0.927 for MagCapture and EVSecond, respectively. The median coefficient of variation was 5%, 8%, and 22% for ExoIntact, MagCapture, and EVSecond, respectively. Comparing total CSF and ExoIntact samples revealed 70 differentially expressed proteins in the cardiovascular III panel and 17 in the cell regulation panel. To our knowledge, this is the first time that CSF EVs were analyzed by PEA. In conclusion, analysis of CSF EVs by PEA is feasible, and different isolation kits give distinct results, with ExoIntact showing the highest number of identified proteins with the lowest variability.</p>","PeriodicalId":509625,"journal":{"name":"International Journal of Molecular Sciences","volume":" ","pages":""},"PeriodicalIF":5.6,"publicationDate":"2020-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3390/ijms21249425","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38712805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dietary Erythrodiol Modifies Hepatic Transcriptome in Mice in a Sex and Dose-Dependent Way.","authors":"Roubi Abuobeid,&nbsp;Luis Herrera-Marcos,&nbsp;María A Navarro,&nbsp;Carmen Arnal,&nbsp;Roberto Martínez-Beamonte,&nbsp;Joaquín Surra,&nbsp;Jesús Osada","doi":"10.3390/ijms21197331","DOIUrl":"https://doi.org/10.3390/ijms21197331","url":null,"abstract":"<p><p>Erythrodiol is a terpenic compound found in a large number of plants. To test the hypotheses that its long-term administration may influence hepatic transcriptome and this could be influenced by the presence of APOA1-containing high-density lipoproteins (HDL), Western diets containing 0.01% of erythrodiol (10 mg/kg dose) were provided to <i>Apoe</i>- and <i>Apoa1</i>-deficient mice. Hepatic RNA-sequencing was carried out in male <i>Apoe</i>-deficient mice fed purified Western diets differing in the erythrodiol content. The administration of this compound significantly up- regulated 68 and down-regulated 124 genes at the level of 2-fold change. These genes belonged to detoxification processes, protein metabolism and nucleic acid related metabolites. Gene expression changes of 21 selected transcripts were verified by RT-qPCR. <i>Ccl19-ps2</i>, <i>Cyp2b10</i>, <i>Rbm14-rbm4</i>, <i>Sec61g</i>, <i>Tmem81</i>, <i>Prtn3</i>, <i>Amy2a5</i>, <i>Cyp2b9</i> and <i>Mup1</i> showed significant changes by erythrodiol administration. When <i>Cyp2b10</i>, <i>Dmbt1</i>, <i>Cyp2b13</i>, <i>Prtn3 and Cyp2b9</i> were analyzed in female <i>Apoe</i>-deficient mice, no change was observed. Likewise, no significant variation was observed in <i>Apoa1</i>- or in <i>Apoe-</i>deficient mice receiving doses ranging from 0.5 to 5 mg/kg erythrodiol. Our results give evidence that erythrodiol exerts a hepatic transcriptional role, but this is selective in terms of sex and requires a threshold dose. Furthermore, it requires an APOA1-containing HDL.</p>","PeriodicalId":509625,"journal":{"name":"International Journal of Molecular Sciences","volume":" ","pages":""},"PeriodicalIF":5.6,"publicationDate":"2020-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3390/ijms21197331","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38460631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Taurine Administration Recovers Motor and Learning Deficits in an Angelman Syndrome Mouse Model.","authors":"Sara Guzzetti,&nbsp;Luciano Calzari,&nbsp;Lucia Buccarello,&nbsp;Valentina Cesari,&nbsp;Ivan Toschi,&nbsp;Stefania Cattaldo,&nbsp;Alessandro Mauro,&nbsp;Francesca Pregnolato,&nbsp;Silvia Michela Mazzola,&nbsp;Silvia Russo","doi":"10.3390/ijms19041088","DOIUrl":"https://doi.org/10.3390/ijms19041088","url":null,"abstract":"<p><p>Angelman syndrome (AS, MIM 105830) is a rare neurodevelopmental disorder affecting 1:10-20,000 children. Patients show moderate to severe intellectual disability, ataxia and absence of speech. Studies on both post-mortem AS human brains and mouse models revealed dysfunctions in the extra synaptic gamma-aminobutyric acid (GABA) receptors implicated in the pathogenesis. Taurine is a free intracellular sulfur-containing amino acid, abundant in brain, considered an inhibiting neurotransmitter with neuroprotective properties. As taurine acts as an agonist of GABA-A receptors, we aimed at investigating whether it might ameliorate AS symptoms. Since mice weaning, we orally administered 1 g/kg/day taurine in water to <i>Ube3a</i>-deficient mice. To test the improvement of motor and cognitive skills, Rotarod, Novel Object Recognition and Open Field tests were assayed at 7, 14, 21 and 30 weeks, while biochemical tests and amino acid dosages were carried out, respectively, by Western-blot and high-performance liquid chromatography (HPLC) on frozen whole brains. Treatment of <i>Ube3a^m</i>^-/p+ mice with taurine significantly improved motor and learning skills and restored the levels of the post-synaptic PSD-95 and pERK1/2-ERK1/2 ratio to wild type values. No side effects of taurine were observed. Our study indicates taurine administration as a potential therapy to ameliorate motor deficits and learning difficulties in AS.</p>","PeriodicalId":509625,"journal":{"name":"International Journal of Molecular Sciences","volume":" ","pages":""},"PeriodicalIF":5.6,"publicationDate":"2018-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3390/ijms19041088","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35979715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Modulatory Roles of N-glycans in T-Cell-Mediated Autoimmune Diseases.","authors":"Ming-Wei Chien,&nbsp;Shin-Huei Fu,&nbsp;Chao-Yuan Hsu,&nbsp;Yu-Wen Liu,&nbsp;Huey-Kang Sytwu","doi":"10.3390/ijms19030780","DOIUrl":"https://doi.org/10.3390/ijms19030780","url":null,"abstract":"<p><p>Glycosylation is a ubiquitous posttranslational modification of proteins that occurs in the endoplasmic reticulum/Golgi. <i>N</i>-glycans and mucin-type <i>O</i>-glycans are achieved via a series of glycohydrolase- and glycosyltransferase-mediated reactions. Glycosylation modulates immune responses by regulating thymocyte development and T helper cell differentiation. Autoimmune diseases result from an abnormal immune response by self-antigens and subsequently lead to the destruction of the target tissues. The modification of <i>N</i>-glycans has been studied in several animal models of T-cell-mediated autoimmune diseases. This review summarizes and highlights the modulatory effects of <i>N</i>-glycosylation in several autoimmune diseases, including multiple sclerosis, systemic lupus erythematosus, inflammatory bowel disease, and type 1 diabetes mellitus.</p>","PeriodicalId":509625,"journal":{"name":"International Journal of Molecular Sciences","volume":" ","pages":""},"PeriodicalIF":5.6,"publicationDate":"2018-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3390/ijms19030780","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35894429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}