Navid Bakshi, Madhuri Kanavalli, Karolina Z Nowak, Katarzyna J Bandyra
{"title":"Human polynucleotide phosphorylase in mitochondrial RNA metabolism.","authors":"Navid Bakshi, Madhuri Kanavalli, Karolina Z Nowak, Katarzyna J Bandyra","doi":"10.1042/BSR20240504","DOIUrl":"https://doi.org/10.1042/BSR20240504","url":null,"abstract":"<p><p>Ever since its discovery more than 70 years ago, the enzyme polynucleotide phosphorylase (PNPase) has been the subject of intensive research that has highlighted its key functional roles. The enzyme was first described in 1955 for its ability to synthesise RNA from nucleoside diphosphates. This discovery led to a Nobel Prize in Physiology or Medicine in 1959 for using PNPase to synthesise artificial RNA. However, it soon became evident that the primary function of this enzyme, conserved across diverse species, is 3'-5' RNA phosphorolysis rather than polymerisation. Remarkably, over 60 years later, it was discovered that PNPase has an even broader range of functions as it was shown to act as a conditional RNA chaperone in bacteria. In humans, PNPase (hPNPase) is located in mitochondria, where it plays a role in mitochondrial RNA (mtRNA) metabolism, thereby regulating mitochondrial function and the overall cell fitness. In this review, we present the current scope of knowledge of hPNPase, including its structure, subcellular localisation, metabolic activity, roles in mtRNA transport, processing and degradation, and its involvement in apoptosis.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":"45 9","pages":"531-546"},"PeriodicalIF":4.7,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145136349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"High expression of Fgr in the left ventricle attenuates myocardial injury in the infarcted region via regulating the phosphorylation level of PI3K/Akt.","authors":"Dongpu Shao, Zhiguo Zhang, Honglei Ji, Lei Shi","doi":"10.1042/BSR20253737","DOIUrl":"https://doi.org/10.1042/BSR20253737","url":null,"abstract":"<p><p>FGR proto-oncogene (Fgr), a member of the Src family kinases, has garnered attention for its potential involvement in apoptotic signaling, yet its role in cardiovascular diseases, particularly acute myocardial infarction (AMI), remains unexplored. This study sought to investigate whether elevated left ventricular Fgr expression alleviates myocardial injury in the infarcted area and whether this protective mechanism is mediated by modulating phosphoinositide 3-kinase (PI3K)/Akt phosphorylation. The transcriptome-wide association study was initially utilized to screen for susceptibility genes in the left ventricle, with findings validated using bulk-RNA sequencing data from a rat model of left anterior descending coronary artery (LAD) ligation; subsequently, human spatial transcriptomics combined with single-nucleus RNA sequencing data confirmed differential expression of Fgr and PI3K/Akt in the infarcted region. Fgr knockdown via siRNA in H9C2 cells and pharmacological inhibition with TL02-59 in rats were conducted to assess cellular survival and cardiac function, respectively. Fgr emerged as a common candidate gene identified through multi-omics data analysis, with its up-regulation confirmed both in vivo and in vitro. Fgr silencing in an in vitro oxygen-glucose deprivation model significantly reduced cell survival and suppressed PI3K/Akt phosphorylation, whereas TL02-59 administration in rats subjected to LAD ligation impaired post-infarction cardiac function while concurrently inhibiting PI3K/Akt phosphorylation levels. This study demonstrates that Fgr is markedly up-regulated in AMI and exerts cardioprotective effects, possibly through modulation of PI3K/Akt signaling phosphorylation, thereby underscoring its potential as a therapeutic target.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Katherin Contreras-Ramirez, Xiomara López-Legarda, Jorge H Tabares-Guevara, Juan C Hernandez, Freimar Segura-Sánchez, Janny A Villa-Pulgarin
{"title":"Anti-tumor and immunomodulatory activity of Ganoderma parvulum-derived polysaccharides.","authors":"Katherin Contreras-Ramirez, Xiomara López-Legarda, Jorge H Tabares-Guevara, Juan C Hernandez, Freimar Segura-Sánchez, Janny A Villa-Pulgarin","doi":"10.1042/BSR20240113","DOIUrl":"https://doi.org/10.1042/BSR20240113","url":null,"abstract":"<p><p>Polysaccharides have gained considerable attention recently because of their anti-tumor and immunoregulatory properties. Its activity depends on the type of fungus that produces it, the extraction method, and the molecular weight.</p><p><strong>Materials and methods: </strong>This study evaluated the anti-tumor and immunoregulatory properties of Ganoderma parvulum (GP)-derived polysaccharides.</p><p><strong>Results: </strong>GP crude polysaccharides inhibited mice's lymphoma without cytotoxicity. In vitro studies showed that exopolysaccharides (GEPS) and intrapolysaccharides (GIPS) of G. parvulum inhibited the proliferation of tumor cells, but no cell death was observed. Significantly, GEPS and GIPS increased the production of nitric oxide, TNF-α, MCP-1, and IL-10, and an increase in IL-1β, IL-18, and Caspase-1, while NLRP3 was down-regulated. Also, it decreases the production of IL-10 and IL-6.</p><p><strong>Conclusion: </strong>These observations suggest that GP-derived polysaccharides may exert anti-tumor activity primarily by activating the host's immune system via macrophage stimulation.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Evaluating plasma adipokines and their cognate receptors as biomarkers for non-invasive diagnosis of endometrial cancer.","authors":"Rebecca Karkia, Eshwa Zahra, Chaeyeoun Min, Kako Hirai, Evgeny Makarov, Emmanouil Karteris, Jayanta Chatterjee","doi":"10.1042/BSR20253508","DOIUrl":"10.1042/BSR20253508","url":null,"abstract":"<p><p>Endometrial cancer (EC) is the most common gynaecological malignancy in developed countries. Early detection remains challenging, with no established plasma-based biomarkers for clinical use. This study aimed to evaluate plasma adipokines and their receptor expression as diagnostic biomarkers for EC. Plasma levels of leptin, soluble leptin receptor, visfatin and asprosin were quantified in EC and control patients using ELISA. The free leptin index (FLI) was calculated as a ratio of leptin to soluble leptin receptor. Gene expression of corresponding receptors, including leptin receptor (Ob-R), insulin receptor (INSR), glucagon-like peptide-1 receptor [GLP-1 receptor (GLP-1R)], and asprosin-associated receptors, toll-like receptor 4 (TLR4), protein tyrosine phosphatase receptor type D (PTPRD), and olfactory receptor family 4 subfamily M member 1, was assessed by RT-qPCR from total blood. Plasma leptin levels were significantly elevated in EC patients, with the FLI over four times higher than controls (P=0.008). Soluble leptin receptor levels trended lower in EC, though non-significantly. Visfatin and asprosin plasma levels showed non-significant elevations. Gene expression analyses revealed significantly increased levels of GLP-1R, TLR4 and PTPRD in EC patients, suggestive of a diagnostic potential. Notably, plasma biomarker levels were not independently correlated with body mass index (BMI). Elevated FLI and up-regulation of adipokine receptor expression highlight the potential of combining plasma-based and molecular biomarkers for EC diagnosis. However, the lack of independence from BMI and conflicting literature underscores the need for larger, standardised studies to validate these findings and determine clinical applicability.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Kinetic and homology model analysis of diaminopimelate decarboxylase from Cyanothece sp. ATCC 51142: unveiling a key enzyme in lysine biosynthesis.","authors":"Zhi-Min Li, Suhang Chen, Weikang Luo, Fang Wang, Siqi Wang, Liyang Huang, Xinyue Xiong, Congcong Xie, Zhimin Li","doi":"10.1042/BSR20253430","DOIUrl":"10.1042/BSR20253430","url":null,"abstract":"<p><p>Diaminopimelate decarboxylase (DAPDC), a pyridoxal 5'-phosphate (PLP)-dependent enzyme, catalyzes the decarboxylation of diaminopimelate (DAP) to yield L-lysine, a key step in lysine biosynthesis. This present study presents a preliminary characterization of DAPDC encoded by the cce1351 gene in Cyanothece sp. ATCC 51142 (CsDAPDC), focusing on its biochemical properties and model structure characteristics. The enzyme exhibited a peak activity at 30°C and pH 8.0, and the catalytic constant (kcat) and substrate binding affinity Michaelis constant (KM) were determined as 1.68 s-1 and 1.20 mM at the above-mentioned condition, respectively. Homology modeling and molecular docking analysis revealed that Gly286, Gly330, Tyr428, and Asp118 interacted with the PLP cofactor, and Ser249, Tyr372, and Tyr428 interacted with the DAP substrate. Additionally, Cys399, Glu400, and Tyr436 from the other monomer were also involved in binding DAP and PLP. Site-directed mutagenesis confirmed the functional roles of these key residues in catalysis. This work provides valuable insights into the catalytic mechanism of CsDAPDC and highlights the enzyme's potential for applications in metabolic engineering of cyanobacteria for enhanced lysine production.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144941066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Improvement of autochthonous Saccharomyces cerevisiae by rapid laboratory evolution technique of genome shuffling.","authors":"Ravichandra Hospet, Devarajan Thangadurai, Jeyabalan Sangeetha, Natália Cruz-Martins","doi":"10.1042/BSR20253121","DOIUrl":"10.1042/BSR20253121","url":null,"abstract":"<p><p>The process of selecting indigenous Saccharomyces cerevisiae strains as a starter culture for specific fermentation has several requisites, including the assessment of distinct parameters based on desirable and traditional enological criteria. In most wineries, commercial S. cerevisiae strains are used for wine fermentation. However, it is rare to find indigenous S. cerevisiae strains used in wine production, even though these isolates are better adapted to specific regions and are often preferred for producing local fruit wines. Here, the identification and characterization of indigenous S. cerevisiae were carried out by 28S rRNA sequencing, followed by Fourier transform infrared spectroscopy analysis for further confirmation. The strain improvement technique of genome shuffling was incorporated to ameliorate sugar tolerance and enhance alcohol production in the S. cerevisiae RHTD10 strain. As a result, it was observed that the improved strain from the third round of shuffling tolerated sugar stress of 30% and produced 10.14 ± 0.21% of alcohol, which is higher than the wild strain of 7.11 ± 0.22% alcohol.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144815752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Demixing of four simultaneously co-expressed phase-separating proteins in the endoplasmic reticulum lumen.","authors":"Haruki Hasegawa","doi":"10.1042/BSR20253165","DOIUrl":"https://doi.org/10.1042/BSR20253165","url":null,"abstract":"<p><p>Intracellular protein crystallization represents an intriguing form of biomolecular assembly. While the list of intracellularly crystallizing proteins is growing and their physiological roles are being elucidated, the underlying requirements and processes for intracellular crystallogenesis remain largely unknown. To reveal cellular capacity and morphological plasticity to accommodate protein crystals and crystal-like inclusion bodies, this study examines how simultaneously co-expressed phase-separating proteins influence each other's behavior in the endoplasmic reticulum (ER) lumen. To this end, four cargoes were selected based on their ability to produce distinctive inclusion body types and morphologies irrespective of originating species, function, or sequence homology. The co-expressed model proteins independently phase-separated into distinctive inclusions and coexisted in the ER without losing their signature morphologic characteristics. The continued growth of intra-ER protein crystals and droplets suggested that co-expressed cargo proteins were continuously synthesized and folded in the ER, thereby fueling the growth of the corresponding inclusion bodies. Thus, even in the crowded ER environment, each of the four overexpressed cargo proteins can find their mates through self-association and assemble into four unique structures in the ER. This study demonstrates that cells can accommodate up to four distinct types of mesoscale inclusion bodies in the ER lumen simultaneously, and the respective phase-separation events proceed without interfering with each other and without morphological mixing.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":"45 9","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144941055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Structural insights into substrate binding, residue contributions, and catalytic mechanism of phosphopantetheine adenylyltransferase from Helicobacter pylori.","authors":"I-Ting Ko, Yi-Ting Yuan, Cheng-Ju Hsieh, Hui-Ting Hsu, Hsien-Sheng Yin","doi":"10.1042/BSR20241405","DOIUrl":"https://doi.org/10.1042/BSR20241405","url":null,"abstract":"<p><p>Phosphopantetheine adenylyltransferase (PPAT) (PPAT; EC 2.7.3.3) is a key enzyme in coenzyme A (CoA) biosynthesis. It catalyzes the reversible transfer of an adenylyl group from ATP to 4'-phosphopantetheine (Ppant), producing pyrophosphate and 3'-dephospho-CoA (dPCoA). Although the crystal structures of PPATs with various ligands have been studied, the specific contributions of residues to catalytic efficiency remain unclear. Here, we present the crystal structures of Helicobacter pylori PPAT (HpPPAT) in its apo form and complexes with Ppant and ATP. Additionally, we report the structure of the HpPPAT P8A mutant bound to dPCoA, providing the first complete occupancy structure of a PPAT complex across the hexamer. In the HpPPAT:ATP complex structure, critical active site residues Thr10, His18, Arg88, and Arg91, conserved in Escherichia coli PPAT (EcPPAT), are identified. HpPPAT utilizes Pro8, Lys42, and Arg133 for ATP binding. This differs from the binding pattern observed in other bacterial PPATs. Mutations of these residues, except for Thr10 and Lys42, resulted in a complete loss of enzymatic activity. This result highlights their critical roles. Mutating Thr10 and Lys42 to alanine reduced catalytic efficiency compared to WT HpPPAT but retained substantial activity. These residues are expected to orient the nucleophile for an in-line displacement mechanism. Based on structural studies and mutagenesis data with kinetic measurements and insights from other bacterial PPATs, we propose a refined catalytic mechanism for HpPPAT that emphasizes species-specific active-site interactions. This mechanism provides a foundation structure-based drugs H. pylori infections.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":"0 ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144941038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Coregulators determine androgen receptor activity in prostate cancer.","authors":"Kerim Yavuz, Nathan A Lack","doi":"10.1042/BSR20253197","DOIUrl":"https://doi.org/10.1042/BSR20253197","url":null,"abstract":"<p><p>The androgen receptor (AR) is the main driver of nearly all prostate cancer (PCa). It alters gene expression by binding to specific cis-regulatory elements on the DNA. Where the AR binds in the genome determines what genes are expressed. However, the AR cistrome is not static and dramatically changes during PCa initiation and progression to activate distinct transcriptional programs that fuel disease growth and therapeutic resistance. Emerging evidence suggests that these changes in DNA binding are not caused by chromatin accessibility but rather from interactions with AR coregulators. These proteins influence AR at every step of its activity and play a critical role in DNA binding and gene activation. These context-specific coregulator interactions can stabilize AR binding with DNA that has low- to moderate-affinity and also affect locus-specific epigenetic modifications to promote transcription. Given their critical role in this process, alterations to coregulator proteins define the normal and oncogenic cistrome and profoundly affect AR-mediated gene transcription. In this review, we aim to provide a new perspective on the role of AR coregulators in transcriptional activity, how these interactions evolve through different stages of PCa and their potential as therapeutic targets in advanced disease.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":"45 8","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144940991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}