Biochemical and biophysical research communications最新文献

{"title":"Identification and determination of the urinary metabolite of iodotyrosine in vivo","authors":"Cindy Xinyu Ji ,&nbsp;Danae Zonias ,&nbsp;Nafisa Djumaeva ,&nbsp;Ranchu Cheng ,&nbsp;Kawther Salim ,&nbsp;Pouya Alikhani ,&nbsp;Tope Oyelade ,&nbsp;Kevin P. Moore ,&nbsp;José C. Moreno ,&nbsp;Ali R. Mani","doi":"10.1016/j.bbrc.2024.150854","DOIUrl":"10.1016/j.bbrc.2024.150854","url":null,"abstract":"<div><h3>Background</h3><div>Congenital hypothyroidism screening traditionally relies on detecting elevated thyroid-stimulating hormone levels, yet this approach may not detect a specific type of congenital hypothyroidism caused by iodotyrosine dehalogenase-1 (<em>Dehal1</em>) deficiency. The deficiency of this enzyme prevents the deiodination of mono-iodotyrosine (MIT) and di-iodotyrosine (DIT) in the process of iodine recycling. This underscores the potential use of iodotyrosine or its metabolites as non-invasive urinary biomarkers for early diagnosis of congenital hypothyroidism. However, the urinary metabolites of MIT/DIT have not yet been discovered. Thus, this study aimed to identify the urinary metabolites of iodotyrosine in experimental models.</div></div><div><h3>Method</h3><div>Gas chromatography mass spectrometry was used to identify the urinary metabolites of iodotyrosine following intraperitoneal injection of MIT in rats. An isotope dilution mass spectrometric assay was developed for assessment of identified metabolites. Urine samples from <em>Dehal1</em> knockout mice were used to confirm the results.</div></div><div><h3>Results</h3><div>We identified novel iodotyrosine metabolites, 3-iodo-4-hydroxyphenylacetic acid (IHPA), and 3,5-diiodo-4-hydroxyphenylacetic acid (Di-IHPA) as the primary urinary metabolites of MIT and DIT respectively. The concentrations of urinary IHPA and Di-IHPA were significantly higher in <em>Dehal1</em> knockout mice.</div></div><div><h3>Conclusion</h3><div>Our findings suggest that IHPA is detected in larger quantities and may hold more clinical significance than previously identified biomarkers like MIT and DIT, making it a promising candidate for diagnosing congenital hypothyroidism or other conditions associated with iodine recycling inhibition.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histone methyltransferase NSD modulates gene silencing mechanisms on Drosophila chromosome 4","authors":"Donghee Ko ,&nbsp;Kyungju Nam ,&nbsp;Byungjun Kang ,&nbsp;Bokyeong Song ,&nbsp;Jaebum Kim ,&nbsp;Kyoung Sang Cho ,&nbsp;Im-Soon Lee","doi":"10.1016/j.bbrc.2024.150863","DOIUrl":"10.1016/j.bbrc.2024.150863","url":null,"abstract":"<div><div>The nuclear receptor-binding SET domain protein (NSD) gene family encodes histone methyltransferases that mono- and di-methylate lysine 36 on histone H3 (H3K36). Here, we examine the effects of NSD loss-of-function on transcription and heterochromatin formation in <em>Drosophila</em> to elucidate the role of NSD in chromatin structure regulation. Transcriptome analysis showed that <em>NSD</em> deletion activated more genes on chromosome 4, predominantly heterochromatic, than on other chromosomes. We further analyzed the position-effect variegation of fly eyes due to <em>mini-white</em> (<em>mw</em>⁺) transgenes inserted at various chromosomal loci and found that <em>NSD</em> deletion promoted <em>mw</em>⁺ transgene expression on chromosome 4. Additionally, <em>NSD</em> deletion reduced the binding of heterochromatin markers HP1a and H3K9 to chromosome 4. These findings suggest that <em>NSD</em> deletion disrupts chromosome 4 heterochromatin structure by reducing HP1a binding, implying NSD's role as an epigenetic regulator of chromosome 4 silencing.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493904","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":"Protein mimics of fusion core from SARS-CoV-1 can inhibit SARS-CoV-2 entry","authors":"Yancheng Zhan ,&nbsp;Moxuan Li ,&nbsp;Rui Gong","doi":"10.1016/j.bbrc.2024.150857","DOIUrl":"10.1016/j.bbrc.2024.150857","url":null,"abstract":"<div><div>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a member of the genus Betacoronavirus (subgenus Sarbecovirus) and shares significant genomic and phylogenetic similarities with severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1). SARS-CoV-2 infection occurs through membrane fusion between the virus and host cell membranes, which is facilitated by the spike glycoprotein subunit 2 (S2). The folding of three heptad-repeat regions 1 (HR1) into a central trimeric core structure, along with the binding of three heptad-repeat regions 2 (HR2) in an antiparallel manner within the groove formed between the HR1 regions, which provides the driving force for membrane fusion. In this study, trimeric and monomeric six-helix bundles (6HB) were created by combining various truncations of the sequences from SARS-CoV-2 HR1 and HR2. In addition, monomeric five-helix bundles (5HB) were constructed using a similar method. Finally, we demonstrated a protein mimic, 5HB_V1 (from SARS-CoV-1), that exhibits activity in inhibiting SARS-CoV-2. These findings suggest a strategy to design monomeric 6HB and 5HB based on the SARS-CoV-2 fusion core: maintain the flanking sequences outside the α-helix region in HR2 and introduce point mutations to enhance hydrogen bonding between the helix bundles. The 5HB could be a target for designing new inhibitors against SARS-CoV-1 and SARS-CoV-2.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142534857","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":"Falcarindiol improves functional recovery and alleviates neuroinflammation after spinal cord injury by inhibiting STAT/MAPK signaling pathways","authors":"Lin Cao ,&nbsp;Xiaoli Huang ,&nbsp;Jiangwei Zhu ,&nbsp;Jian Xiao ,&nbsp;Ling Xie","doi":"10.1016/j.bbrc.2024.150860","DOIUrl":"10.1016/j.bbrc.2024.150860","url":null,"abstract":"<div><div>Spinal cord injury (SCI) is a devastating trauma in the central nervous system (CNS), leading to motor and sensory impairment. Neuroinflammation is one of the critical contributors to the progression of secondary injury. Falcarindiol has been reported to efficaciously mitigate lipopolysaccharide (LPS)-mediated inflammation in RAW 264.7 cells. The role of falcarindiol in SCI recovery remains unclear. In this present study, traumatic SCI mice models and LPS-stimulated murine microglia cell line (BV2 cells) were performed to explore the pharmacological effects and the underlying mechanisms of falcarindiol in improving SCI repair with detection of motor function recovery, morphological changes, numbers of survival neurons and protein expression levels of inflammation or apoptosis-related proteins. Our study found that falcarindiol intervention could promote motor function recovery and reduce spinal cord tissue damage in mice following SCI. Mechanistically, falcarindiol intervention suppressed apoptosis-driven neuronal cell death and mitigated inflammatory reactions following SCI. Additionally, falcarindiol inhibited the activation of signal transducer and activator of transcription (STAT) and mitogen-activated protein kinases (MAPK) signaling pathways <em>in vivo</em> and <em>in vitro</em>. This suppression of STAT and MAPK activation by falcarindiol was reversed by STAT3 agonist Colivelin TFA and MAPK agonist C16-PAF in BV2 cells, respectively. Moreover, the study further demonstrated that the anti-inflammation role of falcarindiol was obstructed by Colivelin TFA but not by C16-PAF in LPS-stimulated BV2 cells, suggesting that falcarindiol may efficaciously ameliorate neuroinflammation through inhibiting the activation of STAT signaling pathway following SCI. Collectively, our study indicates that falcarindiol may be a novel drug candidate for the treatment and management of SCI.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring marine natural products for identifying putative candidates as EBNA1 inhibitors: An insight from molecular docking, molecular dynamics, and DFT computations","authors":"Mahmoud A.A. Ibrahim ,&nbsp;Alaa M.A. Hassan ,&nbsp;Gamal A.H. Mekhemer ,&nbsp;Peter A. Sidhom ,&nbsp;Mohamed A. El-Tayeb ,&nbsp;Ashraf M.M. Abdelbacki ,&nbsp;Shahzeb Khan ,&nbsp;Mahmoud E.S. Soliman ,&nbsp;Alaa H.M. Abdelrahman","doi":"10.1016/j.bbrc.2024.150856","DOIUrl":"10.1016/j.bbrc.2024.150856","url":null,"abstract":"<div><div>Epstein-Barr virus (EBV), namely a DNA neoplasm virus, is liable for over 1 % of malignant neoplasms involving Hodgkin's and Burkitt's lymphoma as well as ventral cancer. Despite the crucial role of EBV in carcinoma evolution, no treatment has been discovered yet against EBV. Epstein-Barr nuclear antigen 1 (EBNA1), the EBV-encoded latent protein, is produced in all EBV-linked neoplasms and is the only latent protein in these cancer types. EBNA1 protein has multiple roles in the upkeep, reproduction, and EBV genome separation and can thus act as an attractive therapeutic target for treating EBV-related malignancies. In the past few decades, attempts have been made to develop specialized EBNA1 inhibitors to reduce EBNA1 expression or obstruct EBNA1-relied processes, but none has been approved yet. Marine natural products (MNPs) have garnered significant interest as potential sources of antiviral drug candidates. In seeking potent drug candidates to inhibit EBV reproduction, an MNP database containing &gt;14,000 compounds was mined to hunt putative EBNA1 inhibitors using docking computations and molecular dynamics simulations (MDS). On the basis of binding energy (Δ<em>G</em>_binding) estimations over 200 ns MDS, UMHMNP351444649 and UMHMNP134128179 revealed a greater binding affinity towards EBNA1 compared to KWG, with Δ<em>G</em>_binding values of −35.6, −33.3, and −32.4 kcal/mol, respectively. Structural and energetical investigations of UMHMNP351444649 and UMHMNP134128179 complexed with EBNA1 were inspected, unveiling the great constancy of these inhibitors within the EBNA1 binding site. Moreover, the identified MNPs demonstrated favorable physicochemical and medicinal chemistry characteristics. Finally, density functional theory calculations were executed, and the results assured the outcomes obtained from docking computations and MDS. These findings proposed UMHMNP351444649 and UMHMNP134128179 as potential anti-EBV drug candidates that warrant further <em>in-vitro</em> and <em>in-vivo</em> assays.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493892","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":"HMGA2 regulates GPX4 expression and ferroptosis in prostate cancer cells","authors":"Precious Elechi Dike ,&nbsp;Bor-Jang Hwang ,&nbsp;Taaliah Campbell ,&nbsp;Mojisoluwa Awolowo ,&nbsp;Bethtrice Elliott ,&nbsp;Valerie Odero-Marah","doi":"10.1016/j.bbrc.2024.150859","DOIUrl":"10.1016/j.bbrc.2024.150859","url":null,"abstract":"<div><div>Prostate cancer (PCa) remains a significant global health burden and an increase in oxidative stress is associated with cancer progression. High Mobility Group A2 (HMGA2), a chromatin architectural protein, increases oxidative stress and promotes sensitivity to ferroptosis inducers, however, the mechanism is unknown. We investigated the role of HMGA2 in GPX4 regulation and the impact on cellular responses to oxidative stress and ferroptosis sensitivity. We conducted UALCAN database analysis, western blot analysis, and lipid peroxidation assays to determine the relationship between HMGA2 and GPX4 and the levels of lipid reactive oxygen species in a panel of PCa cell lines, including an enzalutamide-resistant cancer cell line (C4–2B MDVR). Our results show an inverse relationship between HMGA2 and GPX4 expression with high HMGA2 and low GPX4 expression associated with higher Gleason score and lower survival probability in prostate adenocarcinoma (PRAD) patients, while low/moderate HMGA2 expression is positively associated with increased GPX4 expression and higher survival probability. Cell lines showed a moderately negative but not statistically significant correlation between HMGA2 and GPX4 expression, however, PC3 and DU145 PCa cells display higher lipid peroxides concomitant with higher endogenous levels of HMGA2 and low GPX4. Overexpression of wild-type HMGA2 in LNCaP and 22Rv1 cells leads to higher HMGA2 expression compared to Neo control and is associated with higher SLC7A11 and GPX4 expression, while interestingly truncated HMGA2 overexpression in LNCaP and 22Rv1 cells coincides with higher HMGA2 and reduced GPX4 expression, leading to increased lipid peroxides and susceptibility to ferroptosis. Overexpression of wild-type and truncated HMGA2 in 22Rv1 cells increases SLC7A11 mRNA yet differing GPX4 protein expression suggests posttranslational regulation of GPX4. Moreover, enzalutamide-resistant C4–2B MDVR cells display higher HMGA2 levels compared to C4–2B cells, as well as sensitivity to RSL3 ferroptosis inducer, which is partially reversed by ferroptosis inhibitor, ferrostatin-1. Interestingly, GPX4 expression is higher in C4–2B MDVR cells compared to C4–2B, and HMGA2 knockdown further increases its expression but does not significantly alter its susceptibility to ferroptosis. In conclusion, our study shows that HMGA2 regulation of GPX4 expression is complex and truncated HMGA2 downregulates GPX4 and increases lipid peroxides. Moreover, HMGA2-expressing cells including enzalutamide-resistant cells are susceptible to RSL-3-induced ferroptosis. Thus, ferroptosis sensitivity offers promising insights for the development of targeted therapeutic interventions for aggressive PCa.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493905","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":"Integration of metabolomics and transcriptomics to reveal metabolic characteristics and key targets associated with lncRNA Vof-16 in H19-7 cells","authors":"Wenfang Peng ,&nbsp;Jiajia Wang ,&nbsp;Juan Du,&nbsp;Bojin Xu,&nbsp;Wenyi Li,&nbsp;Shan Huang","doi":"10.1016/j.bbrc.2024.150855","DOIUrl":"10.1016/j.bbrc.2024.150855","url":null,"abstract":"<div><div>Cognitive disorders represent one of the most common chronic complications of diabetes. Our previous study has demonstrated that long non-coding RNA (lncRNA) Vof-16 is upregulated in the hippocampal tissue of streptozotocin (STZ)-induced diabetic rats. Despite this finding, the specific roles and underlying mechanisms of lncRNA Vof-16 in diabetes-related cognitive dysfunction remain largely unexplored. To elucidate the mechanism involved, lncRNA Vof-16 was overexpressed in rat hippocampal cell line H19-7 through lentivirus transfection. We integrated metabolomics and transcriptomics approaches to identify potential targets and metabolic pathways influenced by lncRNA Vof-16. Key proteins and pathways were subsequently validated using western blotting and immunofluorescence staining. Transcriptomics indicated that lncRNA Vof-16 overexpression may modulate autophagic activity in H19-7 cells. Metabolomic profiling revealed that the primary differential metabolic pathways included trehalose degradation, tryptophan metabolism, vitamin B6 metabolism, glycolysis, pterine biosynthesis, and the pentose phosphate pathway. Ingenuity Pathway Analysis (IPA) of gene-metabolite networks demonstrated that the high lncRNA Vof-16 expression group exhibited a significantly higher association with autophagy compared to the low lncRNA Vof-16 expression group. Western blot results confirmed that lncRNA Vof-16 overexpression led to decreased protein expression levels of ATG3 and ATG12. Specifically, lncRNA Vof-16 reduces autophagy in hippocampal neurons by targeting the elevated levels of phospho-p70S6K, a downstream effector of mTORC1, potentially contributing to the pathogenesis of diabetic cognitive impairment. The construction of gene-metabolite networks may offer promising new strategies for addressing the growing issue of diabetic cognitive impairment.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A diarylheptanoid derivative mediates glycogen synthase kinase 3β to promote the porcine muscle satellite cell proliferation: Implications for cultured meat production","authors":"Utid Suriya ,&nbsp;Ratchakrit Srikuea ,&nbsp;Tanida Chokpanuwat ,&nbsp;Kanoknetr Suksen ,&nbsp;Wasina Watcharanapapan ,&nbsp;Palida Saleepimol ,&nbsp;Dusit Laohasinnarong ,&nbsp;Apichart Suksamrarn ,&nbsp;Kyaw Zwar Myint ,&nbsp;Tavan Janvilisri ,&nbsp;Arthit Chairoungdua ,&nbsp;Kanit Bhukhai","doi":"10.1016/j.bbrc.2024.150850","DOIUrl":"10.1016/j.bbrc.2024.150850","url":null,"abstract":"<div><div>Skeletal muscle stem cells, or satellite cells, are vital for cultured meat production, driving proliferation and differentiation to form muscle fibers <em>in vitro</em>. However, these abilities are often compromised after long-term <em>in vitro</em> culturing due to a loss of their stemness characteristics. Therefore, effective pharmacological agents that enhance satellite cell proliferation and maintain stemness ability are needed for optimal cell growth for cultured meat production. In this study, the effects of the identified glycogen synthase kinase 3β (GSK3β) inhibitors, ASPP 049, a diarylheptanoid isolated from <em>Curcuma comosa</em> rhizomes, and CHIR 99021 on porcine muscle satellite cell (PMSC) proliferation and Wnt/β-catenin signaling pathway were investigated. We found that both compounds enhanced cell viability and proliferation while preserving the stemness marker, as evidenced by increased expression of the skeletal muscle stem cell marker, Pax7 protein. Molecular dynamics simulations showed that ASPP 049 and CHIR 99021 exhibited differing binding affinities, primarily through hydrophobic interactions, suggesting potential for the design of more potent inhibitors in the future. Despite its weaker binding, ASPP 049 still showed significant effects on the regulation of the Wnt/β-catenin signaling pathway via increased phosphorylation of GSK3β at Ser9 and decreased the phosphorylation of β-catenin at Ser33, Ser37, and Thr41, thereby subsequently activating Wnt transcriptional activity. This study highlights the potential of ASPP 049 and CHIR 99021 to enhance PMSC proliferation and maintain stemness ability, offering a promising avenue for improving cultured meat production.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142534856","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":"Possibility of refining carotenoid geometrical isomer analysis utilizing DFT-based quantum chemical calculations","authors":"Yasushi Honda ,&nbsp;Antara Ghosh ,&nbsp;Yasuhiro Nishida ,&nbsp;Masaki Honda","doi":"10.1016/j.bbrc.2024.150858","DOIUrl":"10.1016/j.bbrc.2024.150858","url":null,"abstract":"<div><div>We performed quantum chemical calculations based on the density functional theory (DFT) for the all-<em>E</em>- and several <em>Z</em>-isomers of three commercially important carotenoids (lycopene, β-carotene, and astaxanthin) and theoretically obtained the UV–Vis spectrum, response factor (determined from absorption intensities of the all-<em>E</em>- and the <em>Z</em>-isomers), and <em>Q</em>-ratio for each carotenoid isomer. The calculated spectra reproduced the experimental spectral shapes (e.g., the appearance of the <em>Z</em>-peaks and the blue shift of the main peaks for the <em>Z</em>-isomers) very well. The calculated response factors and <em>Q</em>-ratios also showed good agreement with reported values. Notably, response factors, which are difficult to determine experimentally, were well reproduced. These results suggest that quantum chemical calculations can be an effective tool for refining quantitative analysis and obtaining spectral data for carotenoids for which standards are difficult to obtain.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493895","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":"Histone deacetylase inhibition disrupts the molecular signature of the glioblastoma secretome related to extracellular vesicle-associated proteins and targets RAB7a and RAB14 in vitro","authors":"Ana Luiza Ferreira ,&nbsp;Aline Menezes ,&nbsp;Vanessa Sandim ,&nbsp;Robson de Queiroz Monteiro ,&nbsp;Fábio César Sousa Nogueira ,&nbsp;Joseph Albert Medeiros Evaristo ,&nbsp;Denise de Abreu Pereira ,&nbsp;Katia Carneiro","doi":"10.1016/j.bbrc.2024.150847","DOIUrl":"10.1016/j.bbrc.2024.150847","url":null,"abstract":"<div><div>Glioblastoma (GBM) is the most aggressive brain tumor with a poor prognosis. While Histone Deacetylase inhibitors have shown promising results in inhibiting cancer cell invasion and promoting apoptosis, their effects on GBM secretion, specifically focusing on extracellular vesicles (EVs) secretion, remain largely unexplored. Using label-free NANOLC-MS/MS methodology, we identified significant changes in the abundance of membrane traffic regulatory proteins in the secretome of U87MG cells after the treatment with the HDAC inhibitor Trichostatin A (TSA). <em>In silico</em> analysis showed that TSA treatment disrupted the secretion pattern of EVs-associated proteins and cellular signaling pathways, both qualitatively and quantitatively. Notably, RAB14/RAB7a interaction was only observed in the secretome of cells treated with TSA. <em>In vitro</em> assays revealed that TSA treatment of glioma cells increased EVs secretion and intracellular protein levels of RAB7a and RAB14 without affecting gene expression, suggesting a role of these two EVs-associated proteins in grade IV glioma cells. Additionally, an integrative approach using clinical data highlighted a correlation between DNA mutations affecting vesicle traffic coding-genes and clinical and phenotypic outcomes in glioma patients. These findings provide insights into the interplay between epigenetics and GBM intracellular trafficking, potentially leading to improved strategies for targeting and modifying the complex signaling network established between GBM cells and the tumor cell microenvironment.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493903","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}