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Keywords = porphyrin biosynthesis

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19 pages, 4848 KiB  
Article
Comparative Analysis of Bacteriome in Hair Follicle Layers of Patients with Female Pattern Androgenic Alopecia
by Yujun Park, Seoyeon Kyung, Seyoung Mun, Byung Sun Yu, Kyengeui Yun, Chaeyun Baek, Dong-Geol Lee, Seunghyun Kang, Soon Re Kim, Ju-Hee Kim, Yeji Lee, Byung-Cheol Park and Kyudong Han
Microorganisms 2025, 13(6), 1365; https://doi.org/10.3390/microorganisms13061365 - 12 Jun 2025
Viewed by 966
Abstract
Androgenetic alopecia (AGA) is the most common form of patterned hair loss, exhibiting gender-specific clinical features. Recent studies highlight the importance of the skin microbiome in maintaining skin health, but the relationship between the hair follicle microbiome and hair loss, particularly AGA, remains [...] Read more.
Androgenetic alopecia (AGA) is the most common form of patterned hair loss, exhibiting gender-specific clinical features. Recent studies highlight the importance of the skin microbiome in maintaining skin health, but the relationship between the hair follicle microbiome and hair loss, particularly AGA, remains understudied. Hair follicle layer samples were collected directly from the crown region of female pattern hair loss (FPHL), male pattern hair loss (MPHL), and healthy adult women (control) groups. Microbial DNA was extracted and analyzed using Illumina 16S rRNA V3–V4 gene amplicon sequencing. Alpha-diversity and beta-diversity analyses and taxonomic and functional profiling were conducted through relative abundance, LEfSe, and PICRUSt2 analyses. The alpha-diversity analysis showed a significant decrease in microbial richness in the hair loss groups. Unweighted UniFrac-based beta-diversity analysis revealed significant clustering between the control group and the FPHL group. Taxonomic profiling and LEfSe analysis identified differences in microbial composition and biomarkers. PICRUSt2 analysis further revealed altered pathways related to porphyrin metabolism, fatty acid biosynthesis, and steroid hormone metabolism. Additionally, differences in microbiome composition and potential functions were found between the FPHL and MPHL groups. This study provides comprehensive insights into the hair follicle microbiome, revealing unique microbial patterns and functional alterations associated with FPHL. Understanding these microbiome characteristics may contribute to targeted approaches for addressing AGA. Further research is warranted. Full article
(This article belongs to the Section Microbiomes)
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13 pages, 2615 KiB  
Article
OmpR Indirectly Regulates Biosynthesis of Xenocoumacin 1 in Xenorhabdus nematophila
by Yunfei Han, Xintong Zhao, Mengru He, Shujing Zhang, Gaijuan Tang and Yonghong Wang
Microorganisms 2025, 13(6), 1360; https://doi.org/10.3390/microorganisms13061360 - 11 Jun 2025
Viewed by 381
Abstract
Xenorhabdus nematophila has excellent potential for application in both medicine and agriculture due to its various active secondary metabolites. The transcriptional regulator OmpR negatively regulates Xenocoumacin 1 (Xcn1), which has wide antimicrobial activity. Here, we expressed and purified OmpR and verified its binding activities [...] Read more.
Xenorhabdus nematophila has excellent potential for application in both medicine and agriculture due to its various active secondary metabolites. The transcriptional regulator OmpR negatively regulates Xenocoumacin 1 (Xcn1), which has wide antimicrobial activity. Here, we expressed and purified OmpR and verified its binding activities to promoters via an electrophoretic mobility shift assay. RNA sequencing was used to analyze the relevance and difference of differentially expressed genes between X. nematophila and its mutant ΔompR. Compared with the WT, 1127 differentially expressed genes were found in ΔompR, while 4150 co-expressed genes were detected. RT-qPCR data validated the RNA-seq results with 20 randomly selected genes. OmpR positively regulates the process of porphyrin metabolism, quorum sensing, β-Lactam resistance and glyoxylate and dicarboxylate metabolism, while negatively regulating the phosphotransferase system, two-component system and bacterial chemotaxis. OmpR indirectly regulates the biosynthesis of Xcn1 by positively regulating the process of glyoxylate metabolism, which consumes energy and precursors, and negatively regulates biomacromolecules biosynthesis, which provides energy and precursors. Overall, this work revealed the indirect effects of OmpR on the biosynthesis of Xcn1, serving as a foundation for future research into the intricate regulatory network of X. nematophila. Full article
(This article belongs to the Section Molecular Microbiology and Immunology)
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23 pages, 3298 KiB  
Article
Construction of a Plasmid-Free Escherichia coli Strain with Enhanced Heme Supply to Produce Active Hemoglobins
by Zihan Zhang, Baodong Hu, Jingwen Zhou, Jianghua Li, Jian Chen, Guocheng Du and Xinrui Zhao
Metabolites 2025, 15(3), 151; https://doi.org/10.3390/metabo15030151 - 23 Feb 2025
Viewed by 730
Abstract
Background: Heme is an important cofactor and plays crucial roles in the correct folding of hemoproteins. The synthesis of heme can be enhanced by the plasmid-based expression of heme biosynthetic genes. However, plasmid-based expression is genetically unstable and requires the utilization of antibiotics [...] Read more.
Background: Heme is an important cofactor and plays crucial roles in the correct folding of hemoproteins. The synthesis of heme can be enhanced by the plasmid-based expression of heme biosynthetic genes. However, plasmid-based expression is genetically unstable and requires the utilization of antibiotics to maintain high copy numbers of plasmids. Methods: The rate-limiting steps in heme biosynthesis were first analyzed based on previous studies and the accumulation of heme intermediates was achieved by adding heme precursor (5-aminolevulinic acid, ALA). Next, the intracellular accumulation of porphyrin was increased by deleting the porphyrin transporter TolC. Finally, the heme synthetic genes were modified by integrating the hemA and hemL genes into the cheW and yciQ locus, assembling the rate-limiting enzymes HemC and HemD with RIAD-RIDD tags, replacing the promoters of hemE/hemH genes with the constitutive promoter PJ23100, and deleting the heme degradation gene yfeX. Results: An enhanced heme supply HEME2 strain was obtained with a heme titer of 0.14 mg/L, which was 4.60-fold higher than that of the C41(DE3) strain. The HEME2 strain was applied to produce human hemoglobin and leghemoglobin. The titer and peroxidase activity of human hemoglobin were 1.29-fold and 42.4% higher in the HEME2-hHb strain than the values in the control strain C41-hHb. In addition, the peroxidase activity and heme content of leghemoglobin were increased by 39.2% and 53.4% in the HEME2-sHb strain compared to the values in the control strain C41-sHb. Conclusions: A plasmid-free Escherichia coli C41(DE3) strain capable of efficient and stable heme supply was constructed and can be used for the production of high-active hemoglobins. Full article
(This article belongs to the Section Microbiology and Ecological Metabolomics)
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20 pages, 10152 KiB  
Article
Multiomic Analysis Provided Insights into the Responses of Carbon Sources by Wood-Rotting Fungi Daldinia carpinicola
by Peng Yang, Xingchi Ma, Yu Zhang, Yanan Sun, Hao Yu, Jiandong Han, Meng Ma, Luzhang Wan and Fansheng Cheng
J. Fungi 2025, 11(2), 115; https://doi.org/10.3390/jof11020115 - 4 Feb 2025
Viewed by 1049
Abstract
Daldinia carpinicola is a newly identified species of wood-rotting fungi, with substantial aspects of its biology and ecological function yet to be clarified. A Nanopore third-generation sequencer was employed for de novo genome assembly to examine the genetic characteristics. The genome consisted of [...] Read more.
Daldinia carpinicola is a newly identified species of wood-rotting fungi, with substantial aspects of its biology and ecological function yet to be clarified. A Nanopore third-generation sequencer was employed for de novo genome assembly to examine the genetic characteristics. The genome consisted of 35.93 Mb in 46 contigs with a scaffold N50 of 4.384 Mb. Glycoside hydrolases and activities enzymes accounted for a large proportion of the 522 identified carbohydrate-active enzymes (CAZymes), suggesting a strong wood degradation ability. Phylogenetic and comparative analysis revealed a close evolutionary relationship between D. carpinicola and D. bambusicola. D. carpinicola and Hypoxylon fragiforme exhibited significant collinear inter-species genome alignment. Based on transcriptome and metabolomic analyses, D. carpinicola showed a greater ability to utilize sucrose over sawdust as a carbon source, enhancing its growth by activating glycolysis/gluconeogenesis and the citrate cycle. However, compared with sucrose, sawdust as a carbon source activated D. carpinicola amino acid biosynthesis and the production of various secondary metabolites, including diterpenoid, indole alkaloid, folate, porphyrin, and biotin metabolism. The study establishes a theoretical basis for research and applications in biological processes, demonstrating a strategy to modulate the production of secondary metabolites by altering its carbon sources in D. carpinicola. Full article
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19 pages, 5920 KiB  
Article
Rootstock Selection for Resisting Cucumber Fusarium Wilt in Hainan and Corresponding Transcriptome and Metabolome Analysis
by Lingyu Wang, Qiuxia Yi, Panpan Yu, Sunjeet Kumar, Xuyang Zhang, Chenxi Wu, Zhenglong Weng, Mengyu Xing, Kaisen Huo, Yanli Chen and Guopeng Zhu
Plants 2025, 14(3), 359; https://doi.org/10.3390/plants14030359 - 24 Jan 2025
Cited by 1 | Viewed by 1093
Abstract
Soilborne diseases are important problems in modern agricultural production. Fusarium oxysporum f. sp. cucumerinum (FOC) is one of the predominant soilborne pathogens threatening cucumber cultivation, especially in Hainan, China. This study assessed FOC-resistant rootstocks using incidence rate, disease severity index (DSI), and area [...] Read more.
Soilborne diseases are important problems in modern agricultural production. Fusarium oxysporum f. sp. cucumerinum (FOC) is one of the predominant soilborne pathogens threatening cucumber cultivation, especially in Hainan, China. This study assessed FOC-resistant rootstocks using incidence rate, disease severity index (DSI), and area under the disease severity index curve (AUDRC), revealing “JinJiaZhen (Mc-4)” as resistant and “JinGangZhuan 1901 (Mc-18)” as susceptible. Comprehensive transcriptome and metabolome analyses were conducted to investigate the defense mechanisms of these rootstocks, revealing key pathways, such as the mitogen-activated protein kinase (MAPK) signaling pathway, starch and sucrose metabolism, and phenylpropanoid biosynthesis, which are crucial for plant disease resistance. Additionally, the study compared the resistance mechanisms of two other rootstocks, Mc-4 and Mc-18, against FOC infection through transcriptomic and metabolomic analyses. Mc-4 exhibited a higher number of differentially expressed genes (DEGs) related to phenylpropanoid biosynthesis compared to Mc-18. Untargeted metabolomics identified 4093 metabolites, with phenylpropanoid biosynthesis, isoquinoline alkaloid biosynthesis, and porphyrin metabolism as primary annotated pathways. On the sixth day post-inoculation, when the number of DEGs and differentially accumulated metabolites (DAMs) was highest, phenylpropanoid biosynthesis emerged as a key pathway in Mc-4, with 37 DEGs and 8 DAMs identified. Notably, Mc-4 showed upregulated expression of genes encoding enzymes involved in phenylpropanoid biosynthesis and increased accumulation of related metabolites, such as coniferyl-aldehyde, coniferyl alcohol, and coniferyl acetate. These findings highlight the differential defense mechanisms between resistant and sensitive rootstocks and provide insights into plant–pathogen interactions. This study’s results will contribute to the development of better and disease-free cucumber varieties, promoting sustainable agriculture. Full article
(This article belongs to the Special Issue Plant Immune Mechanisms)
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15 pages, 2024 KiB  
Article
Manipulating Intracellular Oxidative Conditions to Enhance Porphyrin Production in Escherichia coli
by Bahareh Arab, Murray Moo-Young, Yilan Liu and C. Perry Chou
Bioengineering 2025, 12(1), 83; https://doi.org/10.3390/bioengineering12010083 - 17 Jan 2025
Cited by 1 | Viewed by 1421
Abstract
Being essential intermediates for the biosynthesis of heme, chlorophyll, and several other biologically critical compounds, porphyrins have wide practical applications. However, up till now, their bio-based production remains challenging. In this study, we identified potential metabolic factors limiting the biosynthesis of type-III stereoisomeric [...] Read more.
Being essential intermediates for the biosynthesis of heme, chlorophyll, and several other biologically critical compounds, porphyrins have wide practical applications. However, up till now, their bio-based production remains challenging. In this study, we identified potential metabolic factors limiting the biosynthesis of type-III stereoisomeric porphyrins in Escherichia coli. To alleviate this limitation, we developed bioprocessing strategies by redirecting more dissimilated carbon flux toward the HemD-enzymatic pathway to enhance the production of type-III uroporphyrin (UP-III), which is a key precursor for heme biosynthesis. Our approaches included the use of antioxidant reagents and strain engineering. Supplementation with ascorbic acid (up to 1 g/L) increased the UP-III/UP-I ratio from 0.62 to 2.57. On the other hand, overexpression of ROS-scavenging genes such as sod- and kat-genes significantly enhanced UP production in E. coli. Notably, overexpression of sodA alone led to a 72.9% increase in total porphyrin production (1.56 g/L) while improving the UP-III/UP-I ratio to 1.94. Our findings highlight the potential of both antioxidant supplementation and strain engineering to mitigate ROS-induced oxidative stress and redirect more dissimilated carbon flux toward the biosynthesis of type-III porphyrins in E. coli. This work offers an effective platform to enhance the bio-based production of porphyrins. Full article
(This article belongs to the Special Issue From Residues to Bio-Based Products through Bioprocess Engineering)
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20 pages, 2383 KiB  
Article
Molecular and Biochemical Mechanisms of Scutellum Color Variation in Bactrocera dorsalis Adults (Diptera: Tephritidae)
by Guangli Wang, Weijun Li, Jiazhan Wu, Ye Xu, Zhaohuan Xu, Qingxiu Xie, Yugui Ge, Haiyan Yang and Xiaozhen Li
Insects 2025, 16(1), 76; https://doi.org/10.3390/insects16010076 - 14 Jan 2025
Viewed by 1126
Abstract
Bactrocera dorsalis (Hendel) is an invasive fruit and vegetable pest, infesting citrus, mango, carambola, etc. We observed that the posterior thoracic scutella of some B. dorsalis adults are yellow, some light yellow, and some white in China. Compared with the B. dorsalis races [...] Read more.
Bactrocera dorsalis (Hendel) is an invasive fruit and vegetable pest, infesting citrus, mango, carambola, etc. We observed that the posterior thoracic scutella of some B. dorsalis adults are yellow, some light yellow, and some white in China. Compared with the B. dorsalis races with a yellow scutellum (YS) and white scutellum (WS), the race with a light-yellow scutellum (LYS) is dominant in citrus and carambola orchards. To reveal genetic correlates among the three races, the genomes of 22 samples (8 with YS, 7 with LYS, and 7 with WS) were sequenced by high-throughput sequencing technology. Single-nucleotide polymorphism (SNP) annotation showed that there were 17,580 non-synonymous mutation sites located in the exonic region. Principal component analysis based on independent SNP data revealed that the SNPs with LYS were more similar to that with YS when compared with WS. Most genes associated with scutellum color variation were involved in three pathways: oxidative phosphorylation, porphyrin and chlorophyll metabolism, and terpenoid backbone biosynthesis. By comparing the sequences among the three races, we screened out 276 differential genes (DGs) in YS vs. WS, 185 DGs in LYS vs. WS, and 104 DGs in YS vs. LYS. Most genes determining color variation in B. dorsalis scutella were located on chromosomes 2–5. Biochemical analysis showed that β-carotene content in YS and LYS was significantly higher than that in WS at any stage of adult days 1, 10, and 20. No significant differences were observed in cytochrome P450 or melanin content in YS, LYS, or WS. Our study provides results on aspects of scutellum color variation in B. dorsalis adults, providing molecular and physiological information for revealing the adaptation and evolution of the B. dorsalis population. Full article
(This article belongs to the Section Insect Pest and Vector Management)
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15 pages, 2093 KiB  
Article
Comparative Transcriptome Analysis Reveals the Impact of a High-Fat Diet on Hepatic Metabolic Function in Tilapia (Oreochromis niloticus)
by Rui Jia, Yiran Hou, Linjun Zhou, Liqiang Zhang, Bing Li and Jian Zhu
Animals 2024, 14(22), 3204; https://doi.org/10.3390/ani14223204 - 8 Nov 2024
Cited by 1 | Viewed by 1271
Abstract
Hepatic steatosis is prevalent among cultured fish, yet the molecular mechanisms remain incompletely understood. This study aimed to assess changes in hepatic metabolic function in tilapia and to explore the underlying molecular mechanisms through transcriptomic analyses. Tilapia were allocated into two groups: a [...] Read more.
Hepatic steatosis is prevalent among cultured fish, yet the molecular mechanisms remain incompletely understood. This study aimed to assess changes in hepatic metabolic function in tilapia and to explore the underlying molecular mechanisms through transcriptomic analyses. Tilapia were allocated into two groups: a normal control (Ctr)-fed group and a high-fat diet (HFD)-fed group. Serum biochemical analyses revealed that HFD feeding led to liver damage and lipid accumulation, characterized by elevated levels of glutamic-pyruvic transaminase (GPT), glutamic-oxaloacetic transaminase (GOT), triglycerides (TGs), and total cholesterol (TC). Transcriptome analysis showed that 538 genes were significantly downregulated, and 460 genes were significantly upregulated in the HFD-fed fish. Gene Ontology (GO) enrichment analysis showed that these differentially expressed genes (DEGs) were apparently involved in the lipid metabolic process and monocarboxylic acid metabolic process. Meanwhile, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated significant alterations in pathways of steroid biosynthesis, porphyrin metabolism, terpenoid backbone biosynthesis, and retinol metabolism after HFD feeding. Additionally, results from Gene Set Enrichment Analysis (GSEA) revealed that gene expression patterns in pathways including oxidative phosphorylation, protein export, protein processing in the endoplasmic reticulum, and ribosome biogenesis were positively enriched in the HFD-fed tilapia. These findings provide novel insights into the mechanisms underlying HFD-induced hepatic dysfunction in fish, contributing to the optimization of feeding strategies in aquaculture. Full article
(This article belongs to the Special Issue Research Progress in Growth, Health and Metabolism of Fishes)
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28 pages, 3458 KiB  
Review
Decoding Cancer through Silencing the Mitochondrial Gatekeeper VDAC1
by Tasleem Arif, Anna Shteinfer-Kuzmine and Varda Shoshan-Barmatz
Biomolecules 2024, 14(10), 1304; https://doi.org/10.3390/biom14101304 - 15 Oct 2024
Cited by 3 | Viewed by 3833
Abstract
Mitochondria serve as central hubs for regulating numerous cellular processes that include metabolism, apoptosis, cell cycle progression, proliferation, differentiation, epigenetics, immune signaling, and aging. The voltage-dependent anion channel 1 (VDAC1) functions as a crucial mitochondrial gatekeeper, controlling the flow of ions, such as [...] Read more.
Mitochondria serve as central hubs for regulating numerous cellular processes that include metabolism, apoptosis, cell cycle progression, proliferation, differentiation, epigenetics, immune signaling, and aging. The voltage-dependent anion channel 1 (VDAC1) functions as a crucial mitochondrial gatekeeper, controlling the flow of ions, such as Ca2+, nucleotides, and metabolites across the outer mitochondrial membrane, and is also integral to mitochondria-mediated apoptosis. VDAC1 functions in regulating ATP production, Ca2+ homeostasis, and apoptosis, which are essential for maintaining mitochondrial function and overall cellular health. Most cancer cells undergo metabolic reprogramming, often referred to as the “Warburg effect”, supplying tumors with energy and precursors for the biosynthesis of nucleic acids, phospholipids, fatty acids, cholesterol, and porphyrins. Given its multifunctional nature and overexpression in many cancers, VDAC1 presents an attractive target for therapeutic intervention. Our research has demonstrated that silencing VDAC1 expression using specific siRNA in various tumor types leads to a metabolic rewiring of the malignant cancer phenotype. This results in a reversal of oncogenic properties that include reduced tumor growth, invasiveness, stemness, epithelial–mesenchymal transition. Additionally, VDAC1 depletion alters the tumor microenvironment by reducing angiogenesis and modifying the expression of extracellular matrix- and structure-related genes, such as collagens and glycoproteins. Furthermore, VDAC1 depletion affects several epigenetic-related enzymes and substrates, including the acetylation-related enzymes SIRT1, SIRT6, and HDAC2, which in turn modify the acetylation and methylation profiles of histone 3 and histone 4. These epigenetic changes can explain the altered expression levels of approximately 4000 genes that are associated with reversing cancer cells oncogenic properties. Given VDAC1’s critical role in regulating metabolic and energy processes, targeting it offers a promising strategy for anti-cancer therapy. We also highlight the role of VDAC1 expression in various disease pathologies, including cardiovascular, neurodegenerative, and viral and bacterial infections, as explored through siRNA targeting VDAC1. Thus, this review underscores the potential of targeting VDAC1 as a strategy for addressing high-energy-demand cancers. By thoroughly understanding VDAC1’s diverse roles in metabolism, energy regulation, mitochondrial functions, and other cellular processes, silencing VDAC1 emerges as a novel and strategic approach to combat cancer. Full article
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12 pages, 1634 KiB  
Article
Radiation Signature in Plasma Metabolome of Total-Body Irradiated Nonhuman Primates and Clinical Patients
by Ales Tichy, Alana D. Carpenter, Yaoxiang Li, Gabriela Rydlova, Pavel Rehulka, Marketa Markova, Marcela Milanova, Vojtech Chmil, Amrita K. Cheema and Vijay K. Singh
Int. J. Mol. Sci. 2024, 25(17), 9208; https://doi.org/10.3390/ijms25179208 - 25 Aug 2024
Cited by 2 | Viewed by 1434
Abstract
In the last decade, geopolitical instability across the globe has increased the risk of a large-scale radiological event, when radiation biomarkers would be needed for an effective triage of an irradiated population. Ionizing radiation elicits a complex response in the proteome, genome, and [...] Read more.
In the last decade, geopolitical instability across the globe has increased the risk of a large-scale radiological event, when radiation biomarkers would be needed for an effective triage of an irradiated population. Ionizing radiation elicits a complex response in the proteome, genome, and metabolome and hence can be leveraged as rapid and sensitive indicators of irradiation-induced damage. We analyzed the plasma of total-body irradiated (TBI) leukemia patients (n = 24) and nonhuman primates (NHPs; n = 10) before and 24 h after irradiation, and we performed a global metabolomic study aiming to provide plasma metabolites as candidate radiation biomarkers for biological dosimetry. Peripheral blood samples were collected according to the appropriate ethical approvals, and metabolites were extracted and analyzed by liquid chromatography mass spectrometry. We identified an array of metabolites significantly altered by irradiation, including bilirubin, cholesterol, and 18-hydroxycorticosterone, which were detected in leukemia patients and NHPs. Pathway analysis showed overlapping perturbations in steroidogenesis, porphyrin metabolism, and steroid hormone biosynthesis and metabolism. Additionally, we observed dysregulation in bile acid biosynthesis and tyrosine metabolism in the TBI patient cohort. This investigation is, to our best knowledge, among the first to provide valuable insights into a comparison between human and NHP irradiation models. The findings from this study could be leveraged for translational biological dosimetry. Full article
(This article belongs to the Collection Feature Paper Collection in Biochemistry)
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19 pages, 2281 KiB  
Article
Harnessing Porphyrin Accumulation in Liver Cancer: Combining Genomic Data and Drug Targeting
by Swamy R. Adapa, Pravin Meshram, Abdus Sami and Rays H. Y. Jiang
Biomolecules 2024, 14(8), 959; https://doi.org/10.3390/biom14080959 - 7 Aug 2024
Cited by 1 | Viewed by 1838
Abstract
The liver, a pivotal organ in human metabolism, serves as a primary site for heme biosynthesis, alongside bone marrow. Maintaining precise control over heme production is paramount in healthy livers to meet high metabolic demands while averting potential toxicity from intermediate metabolites, notably [...] Read more.
The liver, a pivotal organ in human metabolism, serves as a primary site for heme biosynthesis, alongside bone marrow. Maintaining precise control over heme production is paramount in healthy livers to meet high metabolic demands while averting potential toxicity from intermediate metabolites, notably protoporphyrin IX. Intriguingly, our recent research uncovers a disrupted heme biosynthesis process termed ‘porphyrin overdrive’ in cancers that fosters the accumulation of heme intermediates, potentially bolstering tumor survival. Here, we investigate heme and porphyrin metabolism in both healthy and oncogenic human livers, utilizing primary human liver transcriptomics and single-cell RNA sequencing (scRNAseq). Our investigations unveil robust gene expression patterns in heme biosynthesis in healthy livers, supporting electron transport chain (ETC) and cytochrome P450 function without intermediate accumulation. Conversely, liver cancers exhibit rewired heme biosynthesis and a massive downregulation of cytochrome P450 gene expression. Notably, despite diminished drug metabolism, gene expression analysis shows that heme supply to the ETC remains largely unaltered or even elevated with patient cancer progression, suggesting a metabolic priority shift. Liver cancers selectively accumulate intermediates, which are absent in normal tissues, implicating their role in disease advancement as inferred by expression analysis. Furthermore, our findings in genomics establish a link between the aberrant gene expression of porphyrin metabolism and inferior overall survival in aggressive cancers, indicating potential targets for clinical therapy development. We provide in vitro proof-of-concept data on targeting porphyrin overdrive with a drug synergy strategy. Full article
(This article belongs to the Special Issue New Insights into Cytochrome P450s, 2nd Edition)
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11 pages, 4297 KiB  
Article
ALA Promotes Sucrose Accumulation in Early Peach Fruit by Regulating SPS Activity
by Zheng Chen, Xin Guo, Jinhua Du and Mingliang Yu
Curr. Issues Mol. Biol. 2024, 46(8), 7944-7954; https://doi.org/10.3390/cimb46080469 - 24 Jul 2024
Cited by 4 | Viewed by 1118
Abstract
5-Aminolevulinic acid (ALA), as a novel plant growth regulator, is a critical precursor for the biosynthesis of porphyrin compounds in all organisms. Many studies have reported that exogenous ALA treatment could improve fruit sweetness. However, the mechanism by which ALA promotes the increase [...] Read more.
5-Aminolevulinic acid (ALA), as a novel plant growth regulator, is a critical precursor for the biosynthesis of porphyrin compounds in all organisms. Many studies have reported that exogenous ALA treatment could improve fruit sweetness. However, the mechanism by which ALA promotes the increase in sugar content in fruit remains unclear. In this study, we found that ALA significantly promoted sucrose accumulation and SPS (sucrose phosphate synthase) activity in peach fruit. At 14, 28, 42, 50 and 60 days after ALA treatment, sucrose content of fruit was increased by 23%, 43%, 37%, 40% and 16%, respectively, compared with control treatment, and SPS enzyme activity was increased by 21%, 28%, 47%, 37% and 29%, respectively. Correlation analysis showed that the sucrose content of peach fruit under ALA treatment was significantly positively correlated with SPS activity. Subsequently, bioinformatics was used to identify SPS gene family members in peach fruit, and it was found that there were four members of the PpSPS gene family, distributed on chromosomes 1, 7 and 8, named PpSPS1, PpSPS2, PpSPS3 and PpSPS4, respectively. The results of qRT-PCR showed that PpSPS2 and PpSPS3 were highly expressed in response to ALA during fruit development, and the expression of PpSPS2 was positively correlated with SPS activity and sucrose accumulation in peach fruit. The results of tobacco subcellular localization showed that PpSPS2 was mainly distributed in the cytoplasm and nucleus, while PpSPS3 was mainly distributed in the nucleus. The results of this study will lay the foundation for further study on the functions of PpSPS and the regulation of sugar metabolism during the development and ripening of peach fruit by ALA. Full article
(This article belongs to the Section Molecular Plant Sciences)
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18 pages, 3664 KiB  
Article
Uncovering Porphyrin Accumulation in the Tumor Microenvironment
by Swamy R. Adapa, Abdus Sami, Pravin Meshram, Gloria C. Ferreira and Rays H. Y. Jiang
Genes 2024, 15(7), 961; https://doi.org/10.3390/genes15070961 - 22 Jul 2024
Cited by 2 | Viewed by 1922
Abstract
Heme, an iron-containing tetrapyrrole, is essential in almost all organisms. Heme biosynthesis needs to be precisely regulated particularly given the potential cytotoxicity of protoporphyrin IX, the intermediate preceding heme formation. Here, we report on the porphyrin intermediate accumulation within the tumor microenvironment (TME), [...] Read more.
Heme, an iron-containing tetrapyrrole, is essential in almost all organisms. Heme biosynthesis needs to be precisely regulated particularly given the potential cytotoxicity of protoporphyrin IX, the intermediate preceding heme formation. Here, we report on the porphyrin intermediate accumulation within the tumor microenvironment (TME), which we propose to result from dysregulation of heme biosynthesis concomitant with an enhanced cancer survival dependence on mid-step genes, a process we recently termed “Porphyrin Overdrive”. Specifically, porphyrins build up in both lung cancer cells and stromal cells in the TME. Within the TME’s stromal cells, evidence supports cancer-associated fibroblasts (CAFs) actively producing porphyrins through an imbalanced pathway. Conversely, normal tissues exhibit no porphyrin accumulation, and CAFs deprived of tumor cease porphyrin overproduction, indicating that both cancer and tumor-stromal porphyrin overproduction is confined to the cancer-specific tissue niche. The clinical relevance of our findings is implied by establishing a correlation between imbalanced porphyrin production and overall poorer survival in more aggressive cancers. These findings illuminate the anomalous porphyrin dynamics specifically within the tumor microenvironment, suggesting a potential target for therapeutic intervention. Full article
(This article belongs to the Special Issue Genetics of Complex Human Disease 2024)
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18 pages, 5476 KiB  
Article
Transcriptomic Change in the Effects of Dichloroquinolinic Acid on the Development and Growth of Nicotiana tabacum
by Bingjie Li, Anming Ding, Weifeng Wang, Mengmeng Cui, Yuhe Sun, Jing Lv and Changbo Dai
Agronomy 2024, 14(7), 1364; https://doi.org/10.3390/agronomy14071364 - 25 Jun 2024
Viewed by 1017
Abstract
Dichloroquinolinic acid is a hormone-type herbicide widely used to control barnyard grass during crop cultivation. However, it can seriously inhibit the growth of susceptible crops, including tobacco, because it degrades slowly under field conditions. Additionally, the mechanism by which it damages crops is [...] Read more.
Dichloroquinolinic acid is a hormone-type herbicide widely used to control barnyard grass during crop cultivation. However, it can seriously inhibit the growth of susceptible crops, including tobacco, because it degrades slowly under field conditions. Additionally, the mechanism by which it damages crops is unclear. More specifically, the transcriptional changes in plants induced by dichloroquinolinic acid remain unknown. In this study, differentially expressed genes (DEGs) in tobacco treated with dichloroquinolinic acid (varying concentrations and durations) were analyzed and validated to explore the global transcriptome changes. The number of DEGs, which were determined according to the FPKM, varied from 758 to 21,340. The KEGG analysis revealed that many DEGs were involved in starch and sucrose metabolism, phenylpropanoid biosynthesis, photosynthesis, porphyrin and chlorophyll metabolism, and glutathione metabolism. Transcriptomic analyses indicated that dichloroquinolinic acid can inhibit tobacco growth by inhibiting photosynthesis and storage of energy. We discovered that the toxicity mechanism of the hormone herbicide dichloroquinolinic acid differs from that of high concentrations of IAA (Indoleacetic acid), despite studies confirming that the effects of hormone herbicides are consistent with the physiological disturbances and growth inhibition exhibited by plants in IAA overdose. Particularly, dichloroquinolinic acid suppresses photosynthesis while high concentration IAA stimulates nucleotide synthesis and photosynthesis. More importantly, we found by editing the IAA-responsive gene IAA16, tobacco could develop resistance to dichloroquinolinic acid. The results will help clarify plant responses to hormone-type herbicides at the transcriptional level, thereby providing insights into the diversity in the gene’s response to herbicides, the molecular targets of hormone-type herbicides, and the mechanism underlying the susceptibility of tobacco to dichloroquinolinic acid. Accordingly, this study may be helpful for future research to enhance crop resistance to herbicides residues. Full article
(This article belongs to the Section Plant-Crop Biology and Biochemistry)
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20 pages, 4061 KiB  
Article
Transcriptomic Profiling of Sugarcane White Leaf (SCWL) Canes during Maturation Phase
by Karan Lohmaneeratana, Kantinan Leetanasaksakul and Arinthip Thamchaipenet
Plants 2024, 13(11), 1551; https://doi.org/10.3390/plants13111551 - 4 Jun 2024
Cited by 4 | Viewed by 1738
Abstract
Sugarcane white leaf (SCWL) disease, caused by Candidatus Phytoplasma sacchari, results in the most damage to sugarcane plantations. Some SCWL canes can grow unnoticed through the maturation phase, subsequently resulting in an overall low sugar yield, or they can be used accidentally as [...] Read more.
Sugarcane white leaf (SCWL) disease, caused by Candidatus Phytoplasma sacchari, results in the most damage to sugarcane plantations. Some SCWL canes can grow unnoticed through the maturation phase, subsequently resulting in an overall low sugar yield, or they can be used accidentally as seed canes. In this work, 12-month-old SCWL and asymptomatic canes growing in the same field were investigated. An abundance of phytoplasma in SCWL canes affected growth and sugar content as well as alterations of transcriptomic profiles corresponding to several pathways that responded to the infection. Suppression of photosynthesis, porphyrin and chlorophyll metabolism, coupled with an increase in the expression of chlorophyllase, contributed to the reduction in chlorophyll levels and photosynthesis. Blockage of sucrose transport plausibly occurred due to the expression of sugar transporters in leaves but suppression in stalks, resulting in low sugar content in canes. Increased expression of genes associated with MAPK cascades, plant hormone signaling transduction, callose plug formation, the phenylpropanoid pathway, and calcium cascades positively promoted defense mechanisms against phytoplasma colonization by an accumulation of lignin and calcium in response to plant immunity. Significant downregulation of CPK plausibly results in a reduction in antioxidant enzymes and likely facilitates pathogen invasion, while expression of sesquiterpene biosynthesis possibly attracts the insect vectors for transmission, thereby enabling the spread of phytoplasma. Moreover, downregulation of flavonoid biosynthesis potentially intensifies the symptoms of SCWL upon challenge by phytoplasma. These SCWL sugarcane transcriptomic profiles describe the first comprehensive sugarcane–phytoplasma interaction during the harvesting stage. Understanding molecular mechanisms will allow for sustainable management and the prevention of SCWL disease—a crucial benefit to the sugar industry. Full article
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