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1.
Critical aspects of the physiological interactions between lead and magnesium.
Wyparło-Wszelaki, M, Machoń-Grecka, A, Wąsik, M, Dobrakowski, M
Journal of biochemical and molecular toxicology. 2022;(2):e22964
Abstract
Despite technological progress, exposure to lead is an ongoing problem. There are many mechanisms governing the toxic effects of lead on the human body. One such mechanism involves the interaction of this xenobiotic with bivalent metal ions, including magnesium. Literature data suggest that the competition between these elements for binding sites at the molecular and cellular levels, as well as at the systemic level, may represent an important aspect of lead toxicity in the human body. This is especially clear in the context of oxidative stress, immune response, and gene expression modifications. This review aims to summarize current knowledge regarding these issues.
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2.
Antimicrobial peptides in human corneal tissue of patients with fungal keratitis.
Mohammed, I, Mohanty, D, Said, DG, Barik, MR, Reddy, MM, Alsaadi, A, Das, S, Dua, HS, Mittal, R
The British journal of ophthalmology. 2021;(8):1172-1177
Abstract
BACKGROUND Fungal keratitis (FK) is the leading cause of unilateral blindness in the developing world. Antimicrobial peptides (AMPs) have been shown to play an important role on human ocular surface (OS) during bacterial, viral and protozoan infections. In this study, our aim was to profile a spectrum of AMPs in corneal tissue from patients with FK during the active pase of infection and after healing. METHODS OS samples were collected from patients at presentation by impression cytology and scraping. Corneal button specimens were collected from patients undergoing therapeutic penetrating keratoplasty for management of severe FK or healed keratitis. Gene expression of human beta-defensin (HBD)-1, -2, -3 and -9, S100A7, and LL-37 was determined by quantitative real-time PCR. RESULTS Messenger RNA expression (mRNA) for all AMPs was shown to be significantly upregulated in FK samples. The levels of HBD-1 and -2 mRNA were found to be elevated in 18/20 FK samples. Whereas mRNA for HBD-3 and S100A7 was upregulated in 11/20 and HBD9 was increased in 15/20 FK samples. LL-37 mRNA showed moderate upregulation in 7/20 FK samples compared with controls. In healed scar samples, mRNA of all AMPs was found to be low and matching the levels in controls. CONCLUSION AMP expression is a consistent feature of FK, but not all AMPs are equally expressed. HBD-1 and -2 are most consistently expressed and LL-37 the least, suggesting some specificity of AMP expression related to FK. These results will help to identify HBD sequence templates for designing FK-specific peptides to test for therapeutic potential.
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3.
Photosynthesis acclimation under severely fluctuating light conditions allows faster growth of diatoms compared with dinoflagellates.
Zhou, L, Wu, S, Gu, W, Wang, L, Wang, J, Gao, S, Wang, G
BMC plant biology. 2021;(1):164
Abstract
BACKGROUND Diatoms contribute 20% of the global primary production and are adaptable in dynamic environments. Diatoms always bloom earlier in the annual phytoplankton succession instead of dinoflagellates. However, how diatoms acclimate to a dynamic environment, especially under changing light conditions, remains unclear. RESULTS We compared the growth and photosynthesis under fluctuating light conditions of red tide diatom Skeletonema costatum, red tide dinoflagellate Amphidinium carterae, Prorocentrum donghaiense, Karenia mikimotoi, model diatom Phaeodactylum tricornutum, Thalassiosira pseudonana and model dinoflagellate Dinophycae Symbiodinium. Diatoms grew faster and maintained a consistently higher level of photosynthesis. Diatoms were sensitive to the specific inhibitor of Proton Gradient Regulation 5 (PGR5) depending photosynthetic electron flow, which is a crucial mechanism to protect their photosynthetic apparatus under fluctuating light. In contrast, the dinoflagellates were not sensitive to this inhibitor. Therefore, we investigate how PGR5 functions under light fluctuations in the model diatom P. tricornutum by knocking down and overexpressing PGR5. Overexpression of PGR5 reduced the photosystem I acceptor side limitation (Y (NA)) and increased growth rate under severely fluctuating light in contrast to the knockdown of PGR5. CONCLUSION Diatoms acclimatize to fluctuating light conditions better than dinoflagellates. PGR5 in diatoms can regulate their photosynthetic electron flow and accelerate their growth under severe light fluctuation, supporting fast biomass accumulation under dynamic environments in pioneer blooms.
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4.
Potential role of the X circular code in the regulation of gene expression.
Thompson, JD, Ripp, R, Mayer, C, Poch, O, Michel, CJ
Bio Systems. 2021;:104368
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Abstract
The X circular code is a set of 20 trinucleotides (codons) that has been identified in the protein-coding genes of most organisms (bacteria, archaea, eukaryotes, plasmids, viruses). It has been shown previously that the X circular code has the important mathematical property of being an error-correcting code. Thus, motifs of the X circular code, i.e. a series of codons belonging to X and called X motifs, allow identification and maintenance of the reading frame in genes. X motifs are significantly enriched in protein-coding genes, but have also been identified in many transfer RNA (tRNA) genes and in important functional regions of the ribosomal RNA (rRNA), notably in the peptidyl transferase center and the decoding center. Here, we investigate the potential role of X motifs as functional elements of protein-coding genes. First, we identify the codons of the X circular code which are frequent or rare in each domain of life (archaea, bacteria, eukaryota) and show that, for the amino acids with the highest codon bias, the preferred codon is often an X codon. We also observe a correlation between the 20 X codons and the optimal codons/dicodons that have been shown to influence translation efficiency. Then, we examined recently published experimental results concerning gene expression levels in diverse organisms. The approach used is the analysis of X motifs according to their density ds(X), i.e. the number of X motifs per kilobase in a gene sequence s. Surprisingly, this simple parameter identifies several unexpected relations between the X circular code and gene expression. For example, the X motifs are significantly enriched in the minimal gene set belonging to the three domains of life, and in codon-optimized genes. Furthermore, the density of X motifs generally correlates with experimental measures of translation efficiency and mRNA stability. Taken together, these results lead us to propose that the X motifs may represent a genetic signal contributing to the maintenance of the correct reading frame and the optimization and regulation of gene expression.
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Anti-tuberculosis chemotherapy alters TNFR2 expression on CD4+ lymphocytes in both drug-sensitive and -resistant tuberculosis: however, only drug-resistant tuberculosis maintains a pro-inflammatory profile after a long time.
Téllez-Navarrete, NA, Ramon-Luing, LA, Muñoz-Torrico, M, Preciado-García, M, Medina-Quero, K, Hernandez-Pando, R, Chavez-Galan, L
Molecular medicine (Cambridge, Mass.). 2021;(1):76
Abstract
BACKGROUND Tuberculosis (TB) is an infectious disease. During TB, regulatory T cells (Treg) are related to poor prognosis. However, information about conventional and unconventional Treg (cTreg and uTreg, respectively) is limited. The tumour necrosis factor (TNF) and its receptors (TNFR1 and TNFR2) are necessary for mycobacterial infection, and TNFR2 signalling is required to maintain Treg. METHODS A blood sample of drug-susceptible (DS-TB) and drug-resistant tuberculosis (DR-TB) patients was obtained before (basal) and after 2 and 6 months of anti-TB therapy. Expression of TNF, TNFR1, and TNFR2 (transmembrane form, tm) on cTreg, uTreg, activated CD4+ (actCD4+), and CD4+ CD25- (CD4+) T cell subpopulations were evaluated. The main objective was to identify immunological changes associated with sensitive/resistant Mtb strains and with the use of anti-TB therapy. RESULTS We found that after 6 months of anti-TB therapy, both DS- and DR-TB patients have decreased the frequency of cTreg tmTNF+, CD4+ tmTNFR1+ and CD4+ tmTNFR2+. Nevertheless, after 6 months of therapy, only DR-TB patients decreased the frequency of actCD4+ tmTNF+ and actCD4+ tmTNFR2+, exhibited a systemic inflammatory status (high levels of TNF, IFN-γ and IL-12), and their purified CD4+ T cells showed that TNF and TNFR2 are up-regulated at the transcriptional level. Moreover, DS- and DR-TB down-regulated TNFR1 and other proteins associated with Treg (FOXP3 and TGFβ1) in response to the anti-TB therapy. CONCLUSION These results partially explain the differences in the immune response of DS-TB vs DR-TB. The frequency of actCD4+ tmTNFR2+ cells and inflammatory status should be considered in the follow-up of therapy in DR-TB patients.
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6.
Influence of the Bioactive Diet Components on the Gene Expression Regulation.
Mierziak, J, Kostyn, K, Boba, A, Czemplik, M, Kulma, A, Wojtasik, W
Nutrients. 2021;(11)
Abstract
Diet bioactive components, in the concept of nutrigenetics and nutrigenomics, consist of food constituents, which can transfer information from the external environment and influence gene expression in the cell and thus the function of the whole organism. It is crucial to regard food not only as the source of energy and basic nutriments, crucial for living and organism development, but also as the factor influencing health/disease, biochemical mechanisms, and activation of biochemical pathways. Bioactive components of the diet regulate gene expression through changes in the chromatin structure (including DNA methylation and histone modification), non-coding RNA, activation of transcription factors by signalling cascades, or direct ligand binding to the nuclear receptors. Analysis of interactions between diet components and human genome structure and gene activity is a modern approach that will help to better understand these relations and will allow designing dietary guidances, which can help maintain good health.
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Analysis of Inflammatory and Homeostatic Roles of Tissue-resident Macrophages in the Progression of Cholesteatoma by RNA-Seq.
Fang, L, Chen, L, Lin, B, Han, L, Zhu, K, Song, Q
Immunological investigations. 2021;(6):609-621
Abstract
BACKGROUND Tissue-resident macrophages (TRMØs) can act as innate-immune sentinels to protect body against microbe invaders and stimulating materials such as cholesterol crystals in cholesteatoma, as well as to preserve tissue integrity by cleaning unwanted cellular debris. METHODS TRMØs in the incised middle ear tissues were obtained from the patients with cholesteatoma as an experimental group and the patients without cholesteatoma as a control group. Differential gene expression profiling of TRMØs was conducted between two groups by analyzing GO processes, KEGG and GSEA pathways of inflammation, tissue repair and homeostasis. RESULTS The current study showed that 145 of 7060 genes were significantly up-regulated (logFC>2 and FDR <0.05) when compared with the patients without cholesteatoma. GO process, GSEA and Cytoscape analysis of the over-expressed genes illustrated the boosted inflammatory and anti-infection functions of TRMØs existed neutrophil function, leukocyte migration, and adaptive immune response involved receptors and signaling pathways. Whereas the homeostasis and repair functions of TRMØs were affected from up-regulated genes, such as over-expressed keratin-13 that helped form the outer keratinising squamous epithelial layer, and over-expressed MMPs that activated the extracellular matrix molecules to promote inflammation and disturb tissue remodeling. Additionally, 74 down-regulated genes (logFC<-2 and FDR <0.05) also affected the homeostasis and repair functions by affecting extracelluar matrix structure and contractile fibres in TRMØs. CONCLUSIONS The cellular and molecular levels in cholesteatoma is attributable to chronic infection and several disturbed cellular biological processes involving cell integrity and tissue remodeling.
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8.
Fast and furious: insights of back splicing regulation during nascent RNA synthesis.
Xue, W, Ma, XK, Yang, L
Science China. Life sciences. 2021;(7):1050-1061
Abstract
Alternative splicing of eukaryotic precursor (messenger) RNAs in the nucleus not only increases transcriptomic complexity, but also expands proteomic and functional diversity. In addition to basic types of alternative splicing, recent transcriptome-wide analyses have also suggested other new types of non-canonical splicing, such as back splicing and recursive splicing, and their widespread expression across species Increasing lines of evidence have suggested mechanisms for back splicing, including insights from analyses of nascent RNA sequencing. In this review, we discuss our current understanding of back splicing regulation, and highlight its distinct characteristics in processing during nascent RNA synthesis by taking advantage of metabolic tagging nascent RNA sequencing. Features of recursive splicing are also discussed in the perspective of nascent RNA sequencing.
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12(S)-hydroxyheptadeca-5Z,8E,10E-trienoic acid (12-HHT) induces cell growth and improves barrier function through BLT2 interaction in intestinal epithelial Caco-2 cell cultures.
Storniolo, CE, Pequera, M, Company, F, Moreno, JJ
Biochemical pharmacology. 2021;:114663
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Abstract
12(S)-hydroxyheptadeca-5Z,8E,10E-trienoic acid (12-HHT) is an unusual product of the cyclooxygenase pathway that is an endogenous ligand of the low-affinity receptor for leukotriene 4 (LTB4), BLT2. Recent findings suggested that BLT2 possibly plays an important role in the healing of intestinal lesions and the regulation of barrier function. Here, we studied the role of 12-HHT on intestinal epithelial cell growth and the paracellular permeability of intestinal epithelium using Caco-2 cell cultures as experimental model. Our results demonstrated that 12-HHT stimulates intestinal epithelial Caco-2 cell growth through 12-HHT-BLT2-p38-PKC axis and improves paracellular permeability in differentiated Caco-2 cell cultures through the regulation of tight junction elements such as myosin light chain phosphorylation through 12-HHT-BLT2-p38-PKC-MYPT1 axis. Thus, 12-HHT-BLT2 interaction can be involved in intestinal epithelial cell growth and consequently in the epithelium regeneration/repair processes, together with an interesting improvement on the paracellular permeability. These effects appoint that 12-HHT/BLT2 axis may be a suitable strategy for treating wound healing epithelium and barrier-disrupted intestinal processes.
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10.
Regulation of Apolipoprotein A-I Gene Expression in Human Macrophages by Oxidized Low-Density Lipoprotein.
Nekrasova, EV, Larionova, EE, Danko, K, Kuzmina, DO, Shavva, VS, Kudriavtsev, IV, Orlov, SV
Biochemistry. Biokhimiia. 2021;(10):1201-1213
Abstract
Apolipoprotein A-I (ApoA-I) is a key component of reverse cholesterol transport in humans. In the previous studies, we demonstrated expression of the apoA-I gene in human monocytes and macrophages; however, little is known on the regulation of the apoA-I expression in macrophages during the uptake of modified low-density lipoprotein (LDL), which is one of the key processes in the early stages of atherogenesis leading to formation of foam cells. Here, we demonstrate a complex nature of the apoA-I regulation in human macrophages during the uptake of oxidized LDL (oxLDL). Incubation of macrophages with oxLDL induced expression of the apoA-I gene within the first 24 hours, but suppressed it after 48 h. Both effects depended on the interaction of oxLDL with the TLR4 receptor, rather than on the oxLDL uptake by the macrophages. The oxLDL-mediated downregulation of the apoA-I gene depended on the ERK1/2 and JNK cascades, as well as on the NF-κB cascade.