| 1. |
- Burra, Dharani, et al.
(författare)
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RNAseq and Proteomics for Analysing Complex Oomycete Plant Interactions
- 2016
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Ingår i: Current Issues in Molecular Biology. - : MDPI AG. - 1467-3037 .- 1467-3045. ; 19, s. 73-87
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Forskningsöversikt (refereegranskat)abstract
- The oomycetes include some of the most devastating plant pathogens. In this review we discuss the latest results from oomycete and plant studies with emphasis on interaction studies. We focus on the outcomes of RNAseq and proteomics studies and some pitfalls of these approaches. Both pathogenic interactions and biological control are discussed. We underline the usefulness of studies at several levels of complexity from studies of one organism, up to two or more and within agricultural fields (managed settings) up to wild ecosystems. Finally we identify areas of future interest such as detailed interactome studies, dual RNAseq studies, peptide modification studies and population/meta omics with or without biological control agents.
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| 2. |
- El-Helbawy, N. F., et al.
(författare)
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Identification of Age-Associated Transcriptomic Changes Linked to Immunotherapy Response in Primary Melanoma
- 2022
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Ingår i: Current Issues in Molecular Biology. - : MDPI AG. - 1467-3037 .- 1467-3045. ; 44:9, s. 4118-4131
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Tidskriftsartikel (refereegranskat)abstract
- Melanoma is a lethal form of skin cancer. Immunotherapeutic agents such as anti-PD-1 (pembrolizumab and nivolumab) and anti-CTLA-4 (ipilimumab) have revolutionized melanoma treatment; however, drug resistance is rapidly acquired. Several studies have reported an increase in melanoma rates in older patients. Thus, the impact of ageing on transcriptional profiles of melanoma and response to immunotherapy is essential to understand. In this study, the bioinformatic analysis of RNA seq data of old and young melanoma patients receiving immunotherapy identifies the significant upregulation of extra-cellular matrix and cellular adhesion genes in young cohorts, while genes involved in cell proliferation, inflammation, non-canonical Wnt signaling and tyrosine kinase receptor ROR2 are significantly upregulated in the old cohort. Several Treg signature genes as well as transcription factors that are associated with dysfunctional T cell tumor infiltration are differentially expressed. The differential expression of several genes involved in oxidative phosphorylation, glycolysis and glutamine metabolism is also observed. Taken together, this study provides novel findings on the impact of ageing on transcriptional changes in melanoma, and novel therapeutic targets for future studies. © 2022 by the authors.
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| 3. |
- Holmgren, Christian, et al.
(författare)
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Induction of Breast Cancer Cell Apoptosis by TRAIL and Smac Mimetics : Involvement of RIP1 and cFLIP
- 2022
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Ingår i: Current Issues in Molecular Biology. - : MDPI AG. - 1467-3037 .- 1467-3045. ; 44:10, s. 4803-4821
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Tidskriftsartikel (refereegranskat)abstract
- Smac mimetics are a group of compounds able to facilitate cell death in cancer cells. TNF-related apoptosis-inducing ligand (TRAIL) is a death receptor ligand currently explored in combination with Smac mimetics. The molecular mechanisms determining if the combination treatment results in apoptosis are however not fully understood. In this study, we aimed to shed light on these mechanisms in breast cancer cells. Three breast cancer cell lines, MDA-MB-468, CAMA-1 and MCF-7, were used to evaluate the effects of Smac mimetic LCL-161 and TRAIL using cell death assays and Western blot. The combination treatment induces apoptosis and caspase-8 cleavage in MDA-MB-468 and CAMA-1 but not in MCF-7 cells and downregulation of caspase-8 blocked apoptosis. Downregulation, but not kinase inhibition, of receptor-interacting protein 1 (RIP1) suppressed apoptosis in CAMA-1. Apoptosis is preceded by association of RIP1 with caspase-8. Downregulating cellular FLICE-like inhibitory protein (c-FLIP) resulted in increased caspase cleavage and some induction of apoptosis by TRAIL and LCL-161 in MCF-7. In CAMA-1, c-FLIP depletion potentiated TRAIL-induced caspase cleavage and LCL-161 did not increase it further. Our results lend further support to a model where LCL-161 enables the formation of a complex including RIP1 and caspase-8 and circumvents c-FLIP-mediated inhibition of caspase activation.
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| 4. |
- Ibrahim, A. I. M., et al.
(författare)
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Design and Synthesis of Thionated Levofloxacin: Insights into a New Generation of Quinolones with Potential Therapeutic and Analytical Applications
- 2022
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Ingår i: Current Issues in Molecular Biology. - : MDPI AG. - 1467-3037 .- 1467-3045. ; 44:10, s. 4626-4638
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Tidskriftsartikel (refereegranskat)abstract
- Levofloxacin is a widely used fluoroquinolone in several infectious diseases. The structure-activity relationship of levofloxacin has been studied. However, the effect of changing the carbonyl into thiocarbonyl of levofloxacin has not been investigated up to the date of this report. In this work, levofloxacin structure was slightly modified by making a thionated form (compound 3), which was investigated for its antibacterial activity, biocompatibility, and cytotoxicity, as well as spectroscopic properties. The antibacterial susceptibility testing against five different bacteria showed promising minimum inhibitory concentrations (MICs), particularly against B. spizizenii and E. coli, with an MIC value of 1.9 mu M against both bacteria, and 7.8 mu M against P. mirabilis. The molecular docking experiment showed similar binding interactions of both levofloxacin and compound 3 with the active site residues of topoisomerase IV. The biocompatibility and cytotoxicity results revealed that compound 3 was more biocompatible with normal cells and more cytotoxic against cancer cells, compared to levofloxacin. Interestingly, compound 3 also showed an excitation profile with a distinctive absorption peak at lambda(max) 404 nm. Overall, our results suggest that the thionation of quinolones may provide a successful approach toward a new generation with enhanced pharmacokinetic and safety profiles and overall activity as potential antibacterial agents.
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| 5. |
- Kanagarajan, Selvaraju
(författare)
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Plant Metabolomics: Current Initiatives and Future Prospects
- 2023
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Ingår i: Current Issues in Molecular Biology. - 1467-3037 .- 1467-3045. ; 45, s. 8894-8906
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Forskningsöversikt (refereegranskat)abstract
- Plant metabolomics is a rapidly advancing field of plant sciences and systems biology. It involves comprehensive analyses of small molecules (metabolites) in plant tissues and cells. These metabolites include a wide range of compounds, such as sugars, amino acids, organic acids, secondary metabolites (e.g., alkaloids and flavonoids), lipids, and more. Metabolomics allows an understanding of the functional roles of specific metabolites in plants' physiology, development, and responses to biotic and abiotic stresses. It can lead to the identification of metabolites linked with specific traits or functions. Plant metabolic networks and pathways can be better understood with the help of metabolomics. Researchers can determine how plants react to environmental cues or genetic modifications by examining how metabolite profiles change under various crop stages. Metabolomics plays a major role in crop improvement and biotechnology. Integrating metabolomics data with other omics data (genomics, transcriptomics, and proteomics) provides a more comprehensive perspective of plant biology. This systems biology approach enables researchers to understand the complex interactions within organisms.
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| 6. |
- Lazarczyk, Marzena, et al.
(författare)
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Mouse CCL9 Chemokine Acts as Tumor Suppressor in a Murine Model of Colon Cancer
- 2023
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Ingår i: Current Issues in Molecular Biology. - : MDPI. - 1467-3037 .- 1467-3045. ; 45:4, s. 3446-3461
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Tidskriftsartikel (refereegranskat)abstract
- Colorectal cancer is the third most frequently diagnosed cancer in the world. Despite extensive studies and apparent progress in modern strategies for disease control, the treatment options are still not sufficient and effective, mostly due to frequently encountered resistance to immunotherapy of colon cancer patients in common clinical practice. In our study, we aimed to uncover the CCL9 chemokine action employing the murine model of colon cancer to seek new, potential molecular targets that could be promising in the development of colon cancer therapy. Mouse CT26.CL25 colon cancer cell line was used for introducing lentivirus-mediated CCL9 overexpression. The blank control cell line contained an empty vector, while the cell line marked as CCL9+ carried the CCL9-overexpressing vector. Next, cancer cells with empty vector (control) or CCL9-overexpressing cells were injected subcutaneously, and the growing tumors were measured within 2 weeks. Surprisingly, CCL9 contributed to a decline in tumor growth in vivo but had no effect on CT26.CL25 cell proliferation or migration in vitro. Microarray analysis of the collected tumor tissues revealed upregulation of the immune system-related genes in the CCL9 group. Obtained results suggest that CCL9 reveals its anti-proliferative functions by interplay with host immune cells and mediators that were absent in the isolated, in vitro system. Under specific study conditions, we determined unknown features of the murine CCL9 that have so far bee reported to be predominantly pro-oncogenic.
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| 7. |
- Liu, Xin, 1994, et al.
(författare)
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An Accurate Representation of the Number of bZIP Transcription Factors in the Triticum aestivum (Wheat) Genome and the Regulation of Functional Genes during Salt Stress
- 2024
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Ingår i: CURRENT ISSUES IN MOLECULAR BIOLOGY. - 1467-3037 .- 1467-3045. ; 46:5, s. 4417-4436
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Tidskriftsartikel (refereegranskat)abstract
- Climate change is dramatically increasing the overall area of saline soils around the world, which is increasing by approximately two million hectares each year. Soil salinity decreases crop yields and, thereby, makes farming less profitable, potentially causing increased poverty and hunger in many areas. A solution to this problem is increasing the salt tolerance of crop plants. Transcription factors (TFs) within crop plants represent a key to understanding salt tolerance, as these proteins play important roles in the regulation of functional genes linked to salt stress. The basic leucine zipper (bZIP) TF has a well-documented role in the regulation of salt tolerance. To better understand how bZIP TFs are linked to salt tolerance, we performed a genome-wide analysis in wheat using the Chinese spring wheat genome, which has been assembled by the International Wheat Genome Sequencing Consortium. We identified 89 additional bZIP gene sequences, which brings the total of bZIP gene sequences in wheat to 237. The majority of these 237 sequences included a single bZIP protein domain; however, different combinations of five other domains also exist. The bZIP proteins are divided into ten subfamily groups. Using an in silico analysis, we identified five bZIP genes (ABF2, ABF4, ABI5, EMBP1, and VIP1) that were involved in regulating salt stress. By scrutinizing the binding properties to the 2000 bp upstream region, we identified putative functional genes under the regulation of these TFs. Expression analyses of plant tissue that had been treated with or without 100 mM NaCl revealed variable patterns between the TFs and functional genes. For example, an increased expression of ABF4 was correlated with an increased expression of the corresponding functional genes in both root and shoot tissues, whereas VIP1 downregulation in root tissues strongly decreased the expression of two functional genes. Identifying strategies to sustain the expression of the functional genes described in this study could enhance wheat's salt tolerance.
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| 8. |
- Lopez, Job, et al.
(författare)
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Pathogenesis of relapsing fever
- 2022
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Ingår i: Current Issues in Molecular Biology. - : Caister Academic Press. - 1467-3037 .- 1467-3045. ; 42, s. 519-550
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Tidskriftsartikel (refereegranskat)abstract
- Relapsing fever (RF) is caused by several species of Borrelia; all, except two species, are transmitted to humans by soft (argasid) ticks. The species B. recurrentis is transmitted from one human to another by the body louse, while B. miyamotoi is vectored by hard-bodied ixodid tick species. RF Borrelia have several pathogenic features that facilitate invasion and dissemination in the infected host. In this article we discuss the dynamics of vector acquisition and subsequent transmission of RF Borrelia to their vertebrate hosts. We also review taxonomic challenges for RF Borrelia as new species have been isolated throughout the globe. Moreover, aspects of pathogenesis including symptomology, neurotropism, erythrocyte and platelet adhesion are discussed. We expound on RF Borrelia evasion strategies for innate and adaptive immunity, focusing on the most fundamental pathogenetic attributes, multiphasic antigenic variation. Lastly, we review new and emerging species of RF Borrelia and discuss future directions for this global disease.
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| 9. |
- Stam, Frida, et al.
(författare)
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Hydrogen Peroxide Induced Toxicity Is Reversed by the Macrocyclic IRAP-Inhibitor HA08 in Primary Hippocampal Cell Cultures
- 2022
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Ingår i: Current Issues in Molecular Biology. - : MDPI. - 1467-3037 .- 1467-3045. ; 44:10, s. 5000-5012
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Tidskriftsartikel (refereegranskat)abstract
- Angiotensin IV (Ang IV), a metabolite of Angiotensin II, is a bioactive hexapeptide that inhibits the insulin-regulated aminopeptidase (IRAP). This transmembrane zinc metallopeptidase with many biological functions has in recent years emerged as a new pharmacological target. IRAP is expressed in a variety of tissues and can be found in high density in the hippocampus and neocortex, brain regions associated with cognition. Ang IV is known to improve memory tasks in experimental animals. One of the most potent IRAP inhibitors known today is the macrocyclic compound HA08 that is significantly more stable than the endogenous Ang IV. HA08 combines structural elements from Ang IV and the physiological substrates oxytocin and vasopressin, and binds to the catalytic site of IRAP. In the present study we evaluate whether HA08 can restore cell viability in rat primary cells submitted to hydrogen peroxide damage. After damaging the cells with hydrogen peroxide and subsequently treating them with HA08, the conceivable restoring effects of the IRAP inhibitor were assessed. The cellular viability was determined by measuring mitochondrial activity and lactate dehydrogenase (LDH) release. The mitochondrial activity was significantly higher in primary hippocampal cells, whereas the amount of LDH was unaffected. We conclude that the cell viability can be restored in this cell type by blocking IRAP with the potent macrocyclic inhibitor HA08, although the mechanism by which HA08 exerts its effects remains unclear.
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| 10. |
- Aldén, Markus, et al.
(författare)
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Intracellular Reverse Transcription of Pfizer BioNTech COVID-19 mRNA Vaccine BNT162b2 In Vitro in Human Liver Cell Line
- 2022
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Ingår i: Current Issues in Molecular Biology. - : MDPI AG. - 1467-3045. ; 44:3, s. 1115-1126
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Tidskriftsartikel (refereegranskat)abstract
- Preclinical studies of COVID-19 mRNA vaccine BNT162b2, developed by Pfizer and BioNTech, showed reversible hepatic effects in animals that received the BNT162b2 injection. Furthermore, a recent study showed that SARS-CoV-2 RNA can be reverse-transcribed and in-tegrated into the genome of human cells. In this study, we investigated the effect of BNT162b2 on the human liver cell line Huh7 in vitro. Huh7 cells were exposed to BNT162b2, and quantitative PCR was performed on RNA extracted from the cells. We detected high levels of BNT162b2 in Huh7 cells and changes in gene expression of long interspersed nuclear element-1 (LINE-1), which is an endogenous reverse transcriptase. Immunohistochemistry using antibody binding to LINE-1 open reading frame-1 RNA-binding protein (ORFp1) on Huh7 cells treated with BNT162b2 indicated increased nucleus distribution of LINE-1. PCR on genomic DNA of Huh7 cells exposed to BNT162b2 amplified the DNA sequence unique to BNT162b2. Our results indicate a fast up-take of BNT162b2 into human liver cell line Huh7, leading to changes in LINE-1 expression and distribution. We also show that BNT162b2 mRNA is reverse transcribed intracellularly into DNA in as fast as 6 h upon BNT162b2 exposure.
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