Biochemistry and Biophysics Reports最新文献

{"title":"Dynamic strain and β-catenin mediated suppression of interferon responsive genes in quiescent mesenchymal stromal/stem cells","authors":"","doi":"10.1016/j.bbrep.2024.101847","DOIUrl":"10.1016/j.bbrep.2024.101847","url":null,"abstract":"<div><div>Multipotent bone marrow mesenchymal stromal/stem cells (MSCs) respond to mechanical forces. MSCs perceive static and dynamic forces through focal adhesions, as well as cytoskeletal and intranuclear actin. Dynamic strain stimulates nuclear β-catenin (Ctnnb1) that controls gene expression and suppresses osteogenesis. The sensitivity of MSCs to external mechanical forces may be altered by cessation of proliferation, when MSCs begin to express extracellular matrix (ECM) proteins and generate cell/cell contact. Therefore, we assessed whether and how gene expression of proliferating versus quiescent MSCs responds to mechanical stimuli. We used RNA-seq and RT-qPCR to evaluate transcriptomes at 3 h after dynamic strain (200 cycles × 2 % for 20 min) once daily during a two-day time course in naïve (uninduced) MSCs. Transcriptomes of untreated MSCs show that cells become quiescent at day 2 when proliferation markers are downregulated, and ECM related genes are upregulated. On both day 1 and day 2, dynamic strain stimulates expression of oxidative stress related genes (e.g., Nqo1, Prl2c2, Prl2c3). Strikingly, in quiescent MSCs, we observe that dynamic strain suppresses multiple interferon (IFN) responsive genes (e.g., Irf7, Oasl2 and Isg15). IFN responsive genes are activated in MSCs depleted of β-catenin using siRNAs, indicating that β-catenin normally suppresses these genes. Our data indicate that the functional effects of dynamic strain and β-catenin on IFN responsive genes in MSCs are mechanistically coupled. Because dynamic strain and β-catenin reduce the osteogenic potential of MSCs, our findings suggest that IFN responsive genes are novel biomarkers and potential regulators of mechanical responses at early stages of lineage-commitment in post-proliferative MSCs.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142535651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of genes related to fatty acid metabolism in type 2 diabetes mellitus","authors":"","doi":"10.1016/j.bbrep.2024.101849","DOIUrl":"10.1016/j.bbrep.2024.101849","url":null,"abstract":"<div><h3>Aim</h3><div>Fatty acid metabolism is pivotal for lipid synthesis, cellular signaling, and maintaining cell membrane integrity. However, its diagnostic significance in type 2 diabetes mellitus (T2DM) remains unclear.</div></div><div><h3>Materials and methods</h3><div>Three datasets and fatty acid metabolism-related genes were retrieved. Differential expression analysis, WGCNA, machine learning algorithms, diagnostic analysis, and validation were employed to identify key feature genes. Functional analysis, ceRNA network construction, immune microenvironment assessment, and drug prediction were conducted to explore the underlying molecular mechanisms.</div></div><div><h3>Results</h3><div>Six feature genes were identified with strong diagnostic performance and were involved in processes such as ribosome function and fatty acid metabolism. Immune cells, including dendritic cells, eosinophils, and neutrophils, may play a role in the progression of T2DM. ceRNA and drug-target network analysis revealed potential interactions, such as RP11-miR-29a-YTHDF3 and BPA-MSANTD1. The expression patterns of the feature genes, except for YTHDF3, were consistently upregulated in T2DM, aligning with trends observed in the training set.</div></div><div><h3>Conclusion</h3><div>This study investigated the potential molecular mechanisms of six fatty acid metabolism-related genes in T2DM, offering valuable insights that may guide future research and therapeutic development.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142535650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An in-silico approach to target multiple proteins involved in anti-microbial resistance using natural compounds produced by wild mushrooms","authors":"","doi":"10.1016/j.bbrep.2024.101854","DOIUrl":"10.1016/j.bbrep.2024.101854","url":null,"abstract":"<div><div>Bacterial resistance to antibiotics and the number of patients infected by multi-drug-resistant bacteria have increased significantly over the past decade. This study follows a computational approach to identify potential antibacterial compounds from wild mushrooms. Twenty-six known compounds produced by wild mushrooms were docked to assess their affinity with drug targets of antibiotics such as penicillin-binding protein-1a (PBP1a), DNA gyrase, and isoleucyl-tRNA synthetase (ILERS). Docking scores were further validated by multiple receptor conformer (MRC)-based docking studies. Based on the MRC-based docking results, eight molecules were shortlisted for ADMET analysis. Molecular dynamics (MD) simulations were further performed to evaluate the conformational stability of the ligand-protein complexes. Binding energies were computed by the gmx_MMPBSA method. The data were obtained in terms of root-mean square deviation, and root-mean square fluctuation justified the stability of Austrocortilutein A, Austrocortirubin, and Confluentin in complex with several proteins under physiological conditions. Among these, Austrocortilutein A displayed better binding affinity with PBP1a and ILERS when compared with their respective reference ligands. This study is preliminary and aims to help drive the search for compounds that have the capacity to overcome the anti-microbial resistance of prevalent bacteria, using natural compounds produced by wild mushrooms. Further experimental validation is required to justify the clinical use of the studied compounds.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142535649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A diet high in glucose and deficient in dietary fibre causes fat accumulation in the liver without weight gain","authors":"","doi":"10.1016/j.bbrep.2024.101848","DOIUrl":"10.1016/j.bbrep.2024.101848","url":null,"abstract":"<div><div>This study investigated whether a standard calorie diet that is high in glucose and deficient in dietary fibre (described as HGD [high glucose diet]) induces hepatic fat accumulation in mice. We evaluated hepatic steatosis at 7 days and 14 days after the commencement of the HGD. Hepatic triglycerides and areas of oil droplets increased in the HGD group both at day 7 and day 14, whereas weight gain, weight of epididymal fat, and plasma levels of triglycerides were unaffected by HGD consumption. A microarray analysis of the livers revealed that the expression of lipogenesis-related genes was the most affected by HGD consumption. Furthermore, HGD consumption induced the expression of hepatic proteins of fatty acid synthetase, acetyl-CoA carboxylase alpha, and stearoyl-CoA desaturase 1, which are known to be involved in the synthesis of triglyceride. These results indicate that HGD consumption causes fat accumulation in the liver, with an increase in enzymes that are involved in de novo lipogenesis without an accompanying weight or obesity phenotype. Our new findings suggest that HGD consumption could serve as a breeding ground for liver steatosis.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142535146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correlation of SNHG7 and BGL3 expression in patients with de novo acute myeloid leukemia; novel insights into lncRNA effect in PI3K signaling context in AML pathogenesis","authors":"","doi":"10.1016/j.bbrep.2024.101850","DOIUrl":"10.1016/j.bbrep.2024.101850","url":null,"abstract":"<div><h3>Background</h3><div>Acute myeloid leukemia (AML) has been identified as a top priority for discovering a reliable biomarker for treatment improvement and patient outcome prediction due to the heterogeneous nature of AML and the obstacle to find an appropriate treatment strategy for this malignancy. Considering the involvement of long noncoding RNA (lncRNA) SNHG7 and BGL3 found in various cancers, the exact expression pattern of these lncRNAs and their clinical implications in acute myeloid leukemia (AML) continue to be elusive. In order to demonstrate a possible mechanism underlying AML pathogenesis, our goal was to examine BGL3 and SNHG7 lncRNA expressions in PI3K pathway.</div></div><div><h3>Methods</h3><div>This case-control cross-sectional study were conducted on RNA extracted from blood samples of 30 patients diagnosed with AML (Ayatollah-Khansari hospital, Arak, Iran) and 30 (age and gender matched) healthy controls. The expression levels of SNHG7 and BGL3 lncRNAs and their target genes Akt and PTEN, were measured using qRT-PCR. Subsequently, by means of statistical analysis, we determined the plausible correlation between the expressions of the aforementioned genes and lncRNA respectively.</div></div><div><h3>Results</h3><div>In AML samples, a considerable increase in the expression levels of SNHG7 lncRNA and Akr gene was accompanied by a marked reduction in the expression levels of BGL3 lncRNA and PTEN gene. Nevertheless, No significant relationship between the expression level of the indicated genes/lncRNAs and age and sex was found. The remarkable correlation between the expression of genes/lncRNAs and the blast percentage in patients was the notable point in the result of this study.</div></div><div><h3>Conclusions</h3><div>As the most straightforward interpretation of our results, we propose that perhaps the association between SNHG7 and BGL3 built through the interaction between Akt and PTEN may play a crucial role in the AML pathogenesis and any element of this axis could be a potential novel target for further profound treatment strategies. Nonetheless, in the context of Hematological Malignancies, particularly AML, more detailed studies are needed in this area to elucidate the precise role played by this interesting testis-specific pathway.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142445935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of two-dimensional and three-dimensional culture systems and their responses to chemotherapy in cells representing disease progression of high-grade serous ovarian cancer","authors":"","doi":"10.1016/j.bbrep.2024.101838","DOIUrl":"10.1016/j.bbrep.2024.101838","url":null,"abstract":"<div><div>High-grade serous cancer is the most common type of ovarian cancer and is usually diagnosed at advanced stages with high mortality due to recurrence and eventual resistance to standard platinum therapy. The aim of this study was to compare two-dimensional (2D) versus tridimensional (3D) cell culture as a preclinical model of response to carboplatin, paclitaxel and niraparib using PEO1, PEO4 and PEO6 cell lines, which were generated from the same patient along disease progression. Morphologically, cells formed flat adherent layers versus spheroidal structures with different compaction patterns in 2D and 3D respectively. In 2D, apoptosis was rare whereas in 3D cells formed a multilayered structure with an outer layer of live proliferating cells and an inner core of apoptotic cells. Furthermore, a differential capacity to produce ATP was observed among the cell lines in 3D but not in 2D. While response to carboplatin, paclitaxel and niraparib in both settings followed a similar trend, a lower sensitivity was observed in 3D with respect to 2D. Overall, 3D cell culture is likely more reflective of the <em>in vivo</em> cellular tumor behavior and more suitable of therapeutic evaluation given its added complexity absent in 2D.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142445936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of (R)-(−)-Linalool on endothelial damage: Sex differences","authors":"","doi":"10.1016/j.bbrep.2024.101846","DOIUrl":"10.1016/j.bbrep.2024.101846","url":null,"abstract":"<div><div>Oxidative stress and inflammation are responsible for endothelial damage displaying many sex differences. Lipopolysaccharide (LPS) is a pathogenic stimulus that can trigger inflammation, contributing to endothelial dysfunction. Given the scientific evidence on the effectiveness of herbal extracts in managing endothelial dysfunction, we considered the (R)-(−)-Linalool (LIN), an aromatic monoterpene alcohol, as a bioactive phytochemical compound that could prevent and improve endothelial injury. In this study, we evaluated the effect of the LIN on LPS-induced damage in female and male human umbilical vein endothelial cells (FHUVECs and MHUVECs), measuring cell viability, cytokines release (IL-6 and TNF-α), malondialdehyde (MDA), and nitrites.</div><div>LPS significantly reduced viability both in MHUVECs and FHUVECs. Moreover, LPS increased the IL-6, TNF-α, and MDA level only in FHUVECs if compared to basal value; despite that, LPS reduced nitrites only in MHUVECs. LIN alone did not affect the parameters measured except for an increase in nitrites in FHUVECs. Nevertheless, LIN reduced damage and restored endothelium viability reduced by LPS without a clear sex difference. Under LPS, LIN inhibited IL-6 release and reduced MDA levels only in FHUVECs.</div><div>The present data confirm the existence of sex differences in the behavior of HUVECs under LPS conditions. The administration of LIN seems to have a more evident effect on FHUVECs after damage induced by LPS. These LIN effects are important to conduct further well-designed studies on the sex-specific use of this compound on vascular endothelial injury.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142433594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of cell wall binding domains and repeats in Streptococcus pneumoniae phage endolysins: A molecular and diversity analysis","authors":"","doi":"10.1016/j.bbrep.2024.101844","DOIUrl":"10.1016/j.bbrep.2024.101844","url":null,"abstract":"<div><div><em>Streptococcus pneumoniae</em> (pneumococcus) is a multidrug-resistant pathogen associated with pneumonia, otitis media, meningitis and other severe complications that are currently a global threat to human health. The World Health Organization listed <em>Pneumococcus</em> as the fourth of twelve globally prioritized pathogens. Identifying alternatives to antibiotic therapies is urgently needed to combat <em>Pneumococcus</em>. Bacteriophage-derived endolysins can be used as alternative therapeutics due to their bacterial cell wall hydrolyzing capability. In this study, <em>S. pneumoniae</em> phage genomes were screened to create a database of endolysins for molecular modelling and diversity analysis of these lytic proteins. A total of 89 lytic proteins were curated from 81 phage genomes and categorized into eight groups corresponding to their different enzymatically active (EAD) domains and cell wall binding (CBDs) domains. We then constructed three-dimensional structures that provided insights into these endolysins. Group I, II, III, V, and VI endolysins showed conserved catalytic and ion-binding residues similar to existing endolysins available in the Protein Data Bank. While performing structural and sequence analysis with template lysin, an additional cell wall binding repeat was observed in Group II lysin, which was not previously known. Molecular docking performed with choline confirmed the existence of this additional repeat. Group III endolysins showed 99.16 % similarity to LysME-EF1, a lysin derived from <em>Enterococcus faecalis</em>. Furthermore, the comparative computational analysis revealed the existence of CBDs in Group III lysin. This study provides the first insight into the molecular and diversity analysis of <em>S. pneumoniae</em> phage endolysins that could be valuable for developing novel lysin-based therapeutics.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142433724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MYH7, c.2011C>T, is responsible for congenital scoliosis in a Chinese family","authors":"","doi":"10.1016/j.bbrep.2024.101845","DOIUrl":"10.1016/j.bbrep.2024.101845","url":null,"abstract":"<div><div>Neuromuscular scoliosis can be caused by muscular or nervous system dysfunction resulting from genetic variants. Variation in <em>MYH7</em> may cause hypertrophic or dilated cardiomyopathy, skeletal myopathies, or a combination of both; however, scoliosis has rarely been reported. We analyzed a Chinese pedigree with two members suffering from scoliosis. Whole-exome sequencing identified a variant (NM_000257.4:c.2011C &gt; T) of <em>MYH7</em> that cosegregated with the scoliosis phenotype. The variant resulted in a change in the evolutionarily conserved amino acid residue 671 from arginine to cystine (p.R671C), which was predicted to disrupt the structure and function of the motor domain of the slow/β-cardiac myosin heavy chain encoded by <em>MYH7</em>. To date, 913 <em>MYH7</em> variants were associated with cardiomyopathy and/or skeletal myopathies according to the Human Gene Mutation Database. However, only 15 cases of scoliosis have been reported. In our case, the c.2011C &gt; T variant caused scoliosis with 100 % penetrance and hypertrophic cardiomyopathy with partial penetrance.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142433717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of T-2 toxin on intestinal inflammation and transcriptional regulation of inflammatory response in mouse macrophages","authors":"","doi":"10.1016/j.bbrep.2024.101840","DOIUrl":"10.1016/j.bbrep.2024.101840","url":null,"abstract":"<div><div>T-2 toxin, a fungal secondary metabolite produced by toxigenic <em>Fusarium</em> species, poses a significant threat to grain food and feed due to its potential to cause intestinal inflammation in livestock and poultry. Macrophages play a crucial role as integral components of the body's immune system during intestinal inflammation. This study aimed to elucidate the mechanism behind the inflammatory response triggered by T-2 toxin in macrophages. Compared to the control group, gavage administration of T-2 toxin (0.33, 1, and 4 mg kg⁻¹) led to a decrease in body weight and feed intake, along with histopathological alterations in the colon of mice. In addition, T-2 toxin induced the upregulation of macrophage-derived cytokines like IL-1β, IL-6, and TNF-α, as well as a rise in the population of F4/80⁺ macrophages in the colon. T-2 toxin also led to the upregulation of IL-1β, IL-6, and TNF-α in mouse bone marrow-derived macrophages (BMDMs). Furthermore, the transcriptomic analysis of BMDMs exposed to T-2 toxin (10 nM) identified the \"TNF signaling pathway,\" \"Lipid and atherosclerosis,\" \"Epstein-Barr virus infection,\" \"MAPK signaling pathway,\" and the \"NF-kappa B signaling pathway\" as the top five significantly enriched pathways. Subsequently, twelve inflammation-related genes were randomly chosen for validation through quantitative reverse transcription PCR (RT-qPCR), with the results corroborating those from the transcriptomic analysis. The comprehensive analysis of transcriptome data highlights the activation of several signaling pathways associated with the inflammatory response following T-2 toxin-induced BMDMs, offering potential therapeutic targets for the prevention and treatment of T-2 toxin-induced intestinal inflammation.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142433725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}