Biochemistry and Biophysics Reports最新文献

{"title":"Application of liposomal nanoparticles of berberine in photodynamic therapy of A549 lung cancer spheroids","authors":"Kave Moloudi,&nbsp;Heidi Abrahamse,&nbsp;Blassan P. George","doi":"10.1016/j.bbrep.2024.101877","DOIUrl":"10.1016/j.bbrep.2024.101877","url":null,"abstract":"<div><div>Application of liposomes is a critical strategy in drug delivery and increase cellular uptake of drugs having low water solubility. Berberine (BBR) is a bioactive compound found in several plants, including Goldenseal, Barberry, and Oregon grape. It has garnered attention for its various health benefits, particularly in metabolic health and antimicrobial activity. However, one of the challenges associated with BBR is its water solubility. Moreover, BBR has photosensitizing potential via absorbance of light and generation of free radicals. Hence, to improve water solubility and bioavailability, one of the important strategies employed is using lipid-based carriers to enhance solubility. In this study we employed liposomes to deliver BBR in A549 lung cancer spheroid cells to enhance photodynamic therapy efficacies. Results from the EDS and UV–Vis spectroscopy revealed that the BBR had been loaded onto liposomes, with three peaks appearing between 250 and 450 nm. Morphology of Lipo@BBR nanocomplex was in wavy crest shape and the size was 56.99 ± 3.74 nm in SEM and TEM analysis, respectively. FTIR data illustrated that Lipo@BBR has four significant peaks at 1250, 1459, 1736, and 2907 cm⁻¹. DLS data showed that Lipo@BBR has a negative surface charge with a −10.7 Zeta Potential (mV). Additionally, based on Zetasizer measurements, the size of Lipo@BBR complex was 82.7 ± 6.5. Cytotoxicity assay investigation with MTT assay presented that IC₅₀ of Lipo@BBR in PDT was 10 ± 0.5 μg/mL that led to a volume reduction of the A549 spheroids after five sessions of PDT fractionation (total light dose was set at 25 J/cm²). qPCR and immunofluorescence results demonstrated that Lipo@BBR increases the BAX/BCL2 ratio in A549 spheroid cells, hence improving PDT efficiency. In conclusion, our results illustrated that safe dose of Lipo@BBR (10 ± 0.5 μg/mL) in PDT fractionation protocol can be one of the strategies to suppress the tumor volume and cell death proliferation. Authors recommend using Lipo@BBR nanocomplex in PDT fractionation as well as more <em>in vivo</em> investigation is warranted.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"40 ","pages":"Article 101877"},"PeriodicalIF":2.3,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142660840","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":"NOS3 regulates angiogenic potential of human induced pluripotent stem cell-derived endothelial cells","authors":"Anne M. Kong ,&nbsp;Zulhusni A. Idris ,&nbsp;Daniel Urrutia-Cabrera ,&nbsp;Jarmon G. Lees ,&nbsp;Ren Jie Phang ,&nbsp;Geraldine M. Mitchell ,&nbsp;Raymond C.B. Wong ,&nbsp;Shiang Y. Lim","doi":"10.1016/j.bbrep.2024.101876","DOIUrl":"10.1016/j.bbrep.2024.101876","url":null,"abstract":"<div><div>Incorporation of blood capillaries in engineered tissues and their functional connection to host blood vessels is essential for success in engineering vascularized tissues, a process which involves spatial patterning of endothelial cells (ECs) to form functional and integrated vascular networks. Different types of ECs have been employed for vascular network formation and each source offers advantages and disadvantages. While ECs derived from induced pluripotent stem cells (iPSC-ECs) offer advantages over primary ECs in that they can be generated in large quantities for autologous applications, their suitability for disease modelling and cell replacement therapies is not well-explored. The present study compares the angiogenic capacity of iPSC-ECs and primary ECs (cardiac microvascular ECs and lymphatic microvascular ECs) using an <em>in vitro</em> tubulogenesis assay, revealing comparable performance in forming a pseudo-capillary network on Matrigel. Analysis of genes encoding angiogenic factors (<em>VEGFA</em>, <em>VEGFC</em>, <em>VEGFD</em> and <em>ANG</em>), endothelial cell markers (<em>PECAM1</em>, <em>PCDH12</em> and <em>NOS3</em>) and proliferation markers (<em>AURKB</em> and <em>MKI67</em>) indicates a significant positive correlation between <em>NOS3</em> mRNA expression levels and various tubulogenic parameters. Further experimentation using a CRISPR activation system demonstrates a positive impact of <em>NOS3</em> on tubulogenic activity of ECs, suggesting that iPSC-ECs can be enhanced with endogenous <em>NOS3</em> activation. Collectively, these findings highlight the potential of iPSC-ECs in generating vascularized tissues and advancing therapeutic vascularization.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"40 ","pages":"Article 101876"},"PeriodicalIF":2.3,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142660841","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":"StarD5 modulates B cell cholesterol synthesis and IgG1 plasma cell differentiation","authors":"Anuj Tharakan ,&nbsp;Daniel Rodriguez-Agudo ,&nbsp;Sheela Damle ,&nbsp;Genta Kakiyama ,&nbsp;William M. Pandak ,&nbsp;Gregorio Gil ,&nbsp;Rebecca K. Martin","doi":"10.1016/j.bbrep.2024.101873","DOIUrl":"10.1016/j.bbrep.2024.101873","url":null,"abstract":"<div><div>StarD5 is an ER stress protein that binds cholesterol and transfers it to the plasma membrane. It additionally binds and regulates 25-hydroxycholesterol (25-HC) levels. However the full function of the StarD5-25-HC axis is unknown. 25-HC has been recently described as an important suppressor of IgA + plasma cell differentiation in the Peyer's patches, and regulates the switch between germinal center and plasma cells. Since StarD5 regulates 25-HC, we examined the role of StarD5 in B cells using StarD5^−/− mice. We found that StarD5^−/− mice have normal B cell development and antibody production at baseline, but after T-dependent immunization a reduction in class-switched IgG1 germinal center B cells and plasma cells was observed. T-independent immune responses additionally result in a reduction in IgG1 responses and this likely B cell intrinsic. In addition, there was impairment at the T1 to T2 transitional B cell stage after T-independent immunization. In conclusion, StarD5 appears important for IgG1 responses in B cells and may regulate B cell development under stress conditions. Our findings suggest a role for StarD5 as a key regulator of B cell function and activation following immunization.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"40 ","pages":"Article 101873"},"PeriodicalIF":2.3,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142660844","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":"Molecular dynamics studies reveal the structural impacts of LRRK2 R1441C and LRRK2 D1994A mutations in Parkinson's disease","authors":"Ramisha A. Rahman ,&nbsp;Bushra Zaman ,&nbsp;Md Shariful Islam ,&nbsp;Md Harunur Rashid","doi":"10.1016/j.bbrep.2024.101866","DOIUrl":"10.1016/j.bbrep.2024.101866","url":null,"abstract":"<div><div>Parkinson's Disease (PD) is a continuingly deteriorating neurological ailment affecting over 8.5 million patients globally as of 2019, and the numbers are expected to keep rising. To aid in identifying therapeutic targets, molecular dynamics simulations are convenient and cost-effective methods for enriching our knowledge of the molecular pathophysiology of diseases. Many proteins and their corresponding mutations have been identified to contribute to this disease, of which Leucine-rich repeat kinase 2 (LRRK2) is accountable for a significant percentage. Several mutations involving the domains in LRRK2 have been studied, which are known to interfere with various enzymatic processes, ultimately leading to trademark features of PD like aggregation of protein inclusions called Lewy Bodies (LBs), mitochondrial dysfunctions, etc. The precise molecular mechanism of the mutations' pathophysiology is still unclear. This research article looks at the structural effects of mutations, namely the R1441C and D1994A mutations, on the surrounding residues in the protein, offering novel insights into pathophysiological changes at an atomistic level. Our results indicate a gain of electrostatic interactions with a stable αβ motif within the LRR-Roc linker, amongst other changes. This article also highlights the potential involvement and importance of the αβ motif in LRRK2 associated PD.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"40 ","pages":"Article 101866"},"PeriodicalIF":2.3,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142660838","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 immortalized adipose-derived stem cells line from the PIK3CA-related overgrowth spectrum: Unveiling novel therapeutic targets","authors":"Bin Sun ,&nbsp;Hongrui Chen ,&nbsp;Wei Gao ,&nbsp;Yunqi Li ,&nbsp;Chen Hua ,&nbsp;Xiaoxi Lin","doi":"10.1016/j.bbrep.2024.101869","DOIUrl":"10.1016/j.bbrep.2024.101869","url":null,"abstract":"<div><div>PIK3CA-related overgrowth spectrum (PROS) encompasses several rare conditions that lead to overgrowth of various body parts resulting from activating variants in <em>PIK3CA</em>. The absence of ideal cell models significantly impedes progress in PROS research. In this study, we focused on facial infiltrating lipomatosis (FIL) (A disorder within PROS) and aimed to establish and characterize an immortalized PROS cell line. Primary adipose-derived stem cells of FIL were immortal-ized through the transfection of simian virus 40 large T antigen (SV40LT). No significant mor-phological differences were observed in immortalized FIL-ADSCs (Im FIL-ADSCs). Im FIL-ADSCs expressed original mesenchymal surface markers, confirmed by flow cytometry. It harbored <em>PIK3CA</em> mutation and an increased level of PI3K/AKT activation, revealed by sanger sequencing and Western blot respectively. Karyotype analysis revealed a stable chromosome in Im FIL-ADSCs. Higher adipogenic potential and lower osteogenic differentiation properties were de-tected in Im FIL-ADSCs. The proliferative potential of Im FIL-ADSCs increased, whereas malig-nant transformation was not observed in the tumorigenesis assay. Moreover, RNA sequencing further elucidated the role of the transcription factor E2F1 in Im FIL-ADSCs. Drug screening unveiled that STAT3, HSP, EGFR, and NF-kB might be potential therapeutic targets for FIL. This study provided a valuable cellular resource for exploring the underlying pathogenic mechanisms and developing new targeted therapeutic options for PROS.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"40 ","pages":"Article 101869"},"PeriodicalIF":2.3,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142660839","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":"Sophoricoside reduces inflammation in type II collagen-induced arthritis by downregulating NLRP3 signaling","authors":"Youyang Liu ,&nbsp;Yunlu Zhao ,&nbsp;Qi Guo ,&nbsp;Pengfei Wang ,&nbsp;Peixuan Li ,&nbsp;Qingqing Du ,&nbsp;Huazhou Xu ,&nbsp;Qingyin Yu ,&nbsp;Xiaoyi Zhao ,&nbsp;Weiya Zhang ,&nbsp;Shengjun An ,&nbsp;Shuhui Wu","doi":"10.1016/j.bbrep.2024.101867","DOIUrl":"10.1016/j.bbrep.2024.101867","url":null,"abstract":"<div><div>Immune responses, especially NLRP3 signaling in macrophages, play critical roles in rheumatoid arthritis (RA), an autoimmune and inflammatory disease. In this study, we aimed to identify novel therapies for RA. We focused on sophoricoside (SOP), an isoflavone glycoside isolated from <em>Sophora japonica</em>. We predicted the targets of SOP and performed a Gene Ontology analysis to assess its effects. The results suggested that SOP is related to inflammation regulation. We verified these findings by performing <em>in vitro</em> experiments with M1 macrophages differentiated from human peripheral blood monocytes (THP-1 cells). Sophoricoside administration reduced inflammatory activity and NLRP3, Caspase-1, and IL-1β protein levels in macrophages. In addition, SOP and triptolide (TP) was administered intragastrically to male SD rats (n = 40) in a collagen-induced arthritis model. We observed that SOP and TP reduced the inflammatory responses and symptoms of RA. Moreover, unlike TP, SOP showed no liver or kidney toxicity in rats. In conclusion, SOP reduces inflammation in type II collagen-induced arthritis by downregulating NLRP3 signaling and has potential for future clinical applications as an ideal therapy for RA.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"40 ","pages":"Article 101867"},"PeriodicalIF":2.3,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142660842","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":"Kinome-wide CRISPR-Cas9 screens revealed EXOSC10 as a positive regulator of TGF-β signaling","authors":"Dingding Wang ,&nbsp;Xinhao Zhang ,&nbsp;Jianxun Guo ,&nbsp;Weijia Liu ,&nbsp;Yanchi Zhou ,&nbsp;Renxian Wang","doi":"10.1016/j.bbrep.2024.101864","DOIUrl":"10.1016/j.bbrep.2024.101864","url":null,"abstract":"<div><div>The TGF-β signaling pathway is closely associated with human health and disease, and the systematic identification of factors involved in the TGF-β signaling pathway significantly contributes to the understanding and treatment of various diseases. Through kinome-wide CRISPR screen, we identified 13 candidate regulatory targets. Notably, the well-known hallmark genes <em>TGFBR1</em> and <em>TGFBR2</em> emerged as the top two candidate targets. <em>OXSR1</em> and <em>EXOSC10</em> were ranked third and fourth as positive candidate targets, respectively, with <em>EXOSC10</em> being a novel discovery. Importantly, our findings revealed the down-regulation of <em>OXSR1</em> and <em>EXOSC10</em> using CRISPR knockout and RNAi technology effectively suppressed the TGF-β signaling pathway in HeLa and HaCaT cells, providing new insights of TGF-β signaling.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"40 ","pages":"Article 101864"},"PeriodicalIF":2.3,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142660843","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":"Comprehensive characterization and metabolomics to explore the role of hydrocortisone-induced yin deficiency syndrome in mice","authors":"Wenqi Jin ,&nbsp;Lan Yang ,&nbsp;Yuxin Zhang ,&nbsp;Yu Wang ,&nbsp;Yingna Li ,&nbsp;Yiming Zhao ,&nbsp;Liwei Sun ,&nbsp;Fangbing Liu","doi":"10.1016/j.bbrep.2024.101868","DOIUrl":"10.1016/j.bbrep.2024.101868","url":null,"abstract":"<div><div>Yin deficiency syndrome is a theoretical concept of traditional Chinese medicine (TCM) that claims an imbalance between Yin and Yang serves as a potential etiological factor disrupting physiological homeostasis. Its diagnosis in TCM is hindered by the intricate and diverse etiology, resulting in the absence of quantification and standardization. Hence, this study developed a hydrocortisone (HC) induced Yin deficiency syndrome model to investigate the intricate network underlying TCM and elucidate its intervention mechanism. In the findings, the model was characterized by weight loss, elevated drinking water, yellow urination, dry stools, variations in inflammatory factors, and higher levels of oxidative stress. Based on metabolomics, 56 metabolites showed different expressions; among them, 19 were upregulated, and 37 were downregulated. Bioinformatics analysis revealed that identified metabolites are mainly involved in glycerol phospholipid metabolism, pyrimidine metabolism, amino acid biosynthesis, arginine and proline metabolism, and arachidonic acid metabolism pathways. Finally, the metabolic network association confirmed the diagnostic accuracy of the Yin deficiency syndrome as established by HC. We propose for the first time an animal model of Yin deficiency syndrome induced by hydrocortisone in TCM clinical state. This research presents experimental evidence for establishing TCM symptoms and serves as a fundamental basis for the scientific awareness of their etiology.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"40 ","pages":"Article 101868"},"PeriodicalIF":2.3,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142660905","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":"Isolation, characterization, and analysis of pure compounds from Leea macrophylla leaf extract for antibacterial, antidiabetic, cytotoxicity and phytotoxicity","authors":"Md. Selim Reza ,&nbsp;Md. Badrul Islam ,&nbsp;Samia Sharmin ,&nbsp;Farzana Mim ,&nbsp;A.B.M. Hamidul Haque ,&nbsp;Md. Sabir Hossain ,&nbsp;Farha Matin Juliana ,&nbsp;Subrata Banik ,&nbsp;Kazi Rasel Uddin ,&nbsp;Md. Mahmudul Hasan ,&nbsp;Salina Akter ,&nbsp;Afroza Parvin ,&nbsp;Md. Omar Ali Mondal","doi":"10.1016/j.bbrep.2024.101841","DOIUrl":"10.1016/j.bbrep.2024.101841","url":null,"abstract":"<div><div>This research aims to isolate, characterize, and analyze pure compounds from <em>Leea macrophylla</em> leaf extract to investigate its antibacterial, antidiabetic, cytotoxic, and phytotoxic effects. Fresh leaves were collected, dried, and subjected to methanol extraction to obtain a crude extract. From the petroleum ether fraction (PEF) of this extract, three fractions—designated LM1, LM2, and LM3—were prepared using column chromatography. The fractions were tried to be characterized in search for single compound by instrumental technique like ATR-FTIR, ¹H NMR and ¹³C NMR but the ¹H NMR and ¹³C NMR spectra were found complex which were difficult to interpret. To dispel the doubt and get clear idea about the structure, GC-MS analysis of the compounds was carried out whose result showed that all the three extracts were decomposed to several small organic compounds that made the structure elucidation difficult. For this complication, the characterization of the extracts was not possible. Numerous compounds were identified in the methanol extract of <em>L.</em> <em>macrophylla</em> through GC-MS analysis. Among these compounds, Benzene, 1,2,3-trimethyl- and Undecane were found in higher percentages in LM1. LM2 contained Azulene and Bicyclo [4.4.1]undeca-1,3,5,7,9-pentaene, while LM3 was characterized by the presence of 9,9-Dimethoxybicyclo [3.3.1]nona-2,4-dione and 11-(2-Cyclopenten-1-yl)undecanoic acid, among others. The antibacterial activity of these fractions was evaluated against various bacterial strains, demonstrating broad-spectrum effectiveness. LM1 fraction showed the highest antibacterial activity against <em>Proteus</em> sp. With zone of inhibition 25 mm and weak activity against <em>S. sonnei</em> with zone of inhibition 5 mm. LM2 showed the highest activity to both <em>E. cocci</em> and <em>P. aeruginosa</em> with the zone of inhibition of 18 mm and comparatively lower but significant against <em>Proteus</em> sp. LM3 was highly active to <em>S. sonnei</em> with zone of inhibition 20 mm and lower but quite significant against <em>Proteus</em> sp. Moreover, the anti-diabetic potential was assessed, with LM1 showing the strongest α-amylase inhibitory activity, outperforming quercetin (standard). The IC50 values of LM1, LM2, LM3, and quercetin were 57.36 μg/mL, 100.66 μg/mL, 164.92 μg/mL, and 97.45 μg/mL, respectively. In addition, cytotoxicity was assessed using a brine shrimp lethality bioassay, and phytotoxicity was evaluated through seed germination and growth assays. The results suggest that <em>L.</em> <em>macrophylla</em> leaf extracts have potential applications in antimicrobial, antidiabetic, and anti-cancer contexts. This comprehensive study bridges gaps in knowledge surrounding <em>L.</em> <em>macrophylla's</em> multifaceted properties, offering insights into its therapeutic and ecological potential for healthcare and environmental management.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"40 ","pages":"Article 101841"},"PeriodicalIF":2.3,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142660837","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 pan-cancer analysis of the oncogenic function of HMGB1 in human tumors","authors":"Hui-min Yang ,&nbsp;Xiang-ning Zhao ,&nbsp;Xiao-ling Li ,&nbsp;Xi Wang ,&nbsp;Yu Pu ,&nbsp;Dong-kai Wei ,&nbsp;Zhe Li","doi":"10.1016/j.bbrep.2024.101851","DOIUrl":"10.1016/j.bbrep.2024.101851","url":null,"abstract":"<div><h3>Background</h3><div>Although high mobility group box protein 1 (<em>HMGB1</em>) has been researched in relation to cancer in many investigations, a thorough investigation of its role in pan-cancer has yet to be conducted. With the objective of bridging this gap, we delved into the functions of <em>HMGB1</em> in various tumors.</div></div><div><h3>Methods</h3><div>This investigation employed The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases to examine <em>HMGB1</em> gene expression differences and correlation with survival across various human tumors. Then, genetic alterations of <em>HMGB1</em> were analyzed by tool cBioPortal, and immune cell infiltration was assessed. Finally, we gathered clinial samples from 95 patients with various types of solid tumor and performed somatic mutation analysis using panel sequencing. This further highlighted the role of HMGB1 in different solid tumors.</div></div><div><h3>Results</h3><div>There was a notable elevation of <em>HMGB1</em> gene expression in tumor tissues as opposed to non-cancerous tissues across the bulk of tumor types. Elevated <em>HMGB1</em> gene expression had a connection with shorter overall survival, progression-free survival, and disease-free survival in specific tumor types. Genetic alterations of <em>HMGB1</em> suggested that the amplifications and mutations of <em>HMGB1</em> may impact the prognosis of breast cancer (BRCA) and liver hepatocellular carcinoma (LIHC). Both BRCA and mesothelioma (MESO) displayed a connection between the infiltration of cancer-associated fibroblasts (CAFs) and <em>HMGB1</em> gene expression. Moreover, <em>HMGB1</em> co-expression analysis revealed its association with genes involved in RNA splicing, mRNA processing, and modulation of mRNA metabolic processes. Additionally, a pathway analysis by use of the Kyoto Encyclopedia of Genes and Genomes (KEGG) unveiled that <em>HMGB1</em> was implicated in the pathogenic mechanisms of \"Hepatitis B,\" \"Viral Carcinogenesis,\" and \"Hepatocellular Carcinoma.\" Based on somatic mutation analysis of 95 patients with different solid tumors, we found that the frequency of HMGB1 mutations was higher in Liver cancer patients compared to other solid tumors. This finding is consistent with our in-silico study results. Additionally, we discovered that the frequency of HMGB1 mutations ranked among the top 20 mutated genes in the 95 patients’ data, indicating that HMGB1 plays an important role in the development and prognosis of various solid tumors.</div></div><div><h3>Conclusion</h3><div>This pan-cancer study of <em>HMGB1</em> underscores its potential as a signature marker and target for the management of various tumor types.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"40 ","pages":"Article 101851"},"PeriodicalIF":2.3,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142660836","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}