Biochemistry and Cell Biology最新文献

{"title":"Psilocybin alleviates high-glucose and high-lipid-induced skin aging in BJ5Ta fibroblasts.","authors":"Farzaneh Norouzkhani, Esmaeel Ghasemi Gojani, Bo Wang, DongPing Li, Salma Shujat, Aadarsh Shrestha, Rocio Rodriguez-Juarez, Olga Kovalchuk, Igor Kovalchuk","doi":"10.1139/bcb-2025-0250","DOIUrl":"10.1139/bcb-2025-0250","url":null,"abstract":"<p><p>Cellular aging, driven by oxidative stress, mitochondrial dysfunction, and inflammation, is exacerbated by a high-glucose and high-lipid (HGHL) diet, leading to collagen degradation and skin aging. Psilocybin, a naturally occurring compound, has shown potential in reducing symptoms of aging. This study explores the protective effects of psilocybin on BJ-5ta fibroblasts exposed to HGHL, focusing on cellular viability, apoptosis, senescence, the inflammatory responses, and wound healing. First, fibroblasts were exposed to 25 mmol/L glucose and 400 µmol/L palmitic acid to establish cell aging. Then, psilocybin effects were tested in co- and post-treatment with HGHL. Post-treatment with psilocybin at 15 µmol/L (P15) and co-treatment with psilocybin at 10 µmol/L (P10) preserved cellular viability and decreased beta-galactosidase activity. P10 was most effective in reducing apoptosis and alleviating HGHL-induced S phase arrest. P15 also reduced senescence markers and decreased the expression of inflammatory cytokines <i>IL-1β</i>, <i>IL-6</i>, and <i>COX-2</i>. Additionally, psilocybin promoted nonsignificant fibroblast migration, and P10 co-treated with HGHL significantly upregulated <i>elastin</i> gene expression. These findings suggest that psilocybin's antioxidative, anti-inflammatory, and regenerative properties make it a promising natural compound for reducing skin aging, particularly under oxidative stress conditions. Further research is needed to explore its long-term effects, optimal dosages, and clinical applications.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":"1-15"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145312273","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":"Phospholipid Externalization Blockade as an Antitumor Immunotherapy.","authors":"Chao-Yuan Chang","doi":"10.1139/bcb-2025-0320","DOIUrl":"10.1139/bcb-2025-0320","url":null,"abstract":"<p><strong>Background: </strong>In eukaryotic cells, phospholipid asymmetry is actively maintained, with phosphatidylserine (PS) typically confined to the inner leaflet of the plasma membrane (PM), due to the active performance of the PS flippase ATP11/CDC50A complex. However, in the tumor microenvironment (TME), PS exposure on the outer leaflet occurs from multiple sources, including apoptotic tumor cells, necrotic tissue, viable endothelial cells, and tumor-derived exosomes. Especially, in apoptotic cells, the PS scamblase Xkr8 mediates PS externalization. This exposed PS plays a crucial role in immune suppression within the TME. PS binds to receptors on phagocytes, primarily macrophages and dendritic cells (DCs), triggering efferocytosis (the engulfment of PS-positive cells, usually apoptotic cells) and promoting anti-inflammatory responses.</p><p><strong>Method: </strong>To understand the immune suppressive role of PS exposure on tumor cells, we deleted CDC50A, the PS flippase, from the tumor. Thus, in this tumor, PS is constantly on the outer leaflet of PM, called PS^out tumor model. On the contrary, we knocked out Xkr8 from tumor cells. Thus, even tumor cells undergo apoptosis, PS can still stay in the inner leaflet of PM, called PSⁱⁿ tumor model. Taking the advantage of the PSⁱⁿ and PS^out model, we could investigate the anti-tumor immune responses of PS externalization in TME.</p><p><strong>Results: </strong>Using PS^out model, we found that these PS^out tumors exhibited enhanced growth, M2-polarized tumor-associated macrophages (TAMs), and reduced tumor-antigen-specific T cell infiltration. In TME, the PS receptor TIM-3 on TAMs was responsible for PS sensing. Using PSⁱⁿ model, we found that the PSⁱⁿ tumors exhibited increased anti-tumor immunity, featuring suppressed tumor progress, TAM M1 polarization, suppressed IL-10 secretion, and enhanced natural killer (NK) cell cytotoxicity. Thus, blocking PS externalization via targeting Xkr8 could serve as a promising strategy for anti-tumor immunotherapy.</p><p><strong>Therapeutic applications: </strong>However, there is no available Xkr8 inhibitor or direct anti-PS blocking antibody for therapeutic use. Thus, we developed our unique \"PS all-block\" strategy leveraging an engineered protein which binds only to PS, without sending signals to immune receptors, functioning as a dominant negative. The \"PS all-block\" can neutralize PS molecules from all sources without triggering downstream immune suppression pathways. Our data suggested that the \"PS all-block\" was a more effective antitumor immunotherapy compared to our successfully developed Xkr8 inhibition, as Xkr8 targeting only neutralized apoptotic PS, while the \"PS all-block\" approach could neutralize PS from all sources.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":"103 ","pages":"1-11"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145343002","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":"Ophiopogonin D protects against cerebral ischemia-reperfusion injury in rats by inhibiting STAT3 phosphorylation.","authors":"Zheng Tang, Chunmei Liu","doi":"10.1139/bcb-2024-0328","DOIUrl":"10.1139/bcb-2024-0328","url":null,"abstract":"<p><p>Our aim is to explore the protective effect of ophiopogonin D (OPD) on cerebral ischemia/reperfusion injury (CIRI) and its relevant molecular mechanisms. OPD effect on brain injury of CIRI rats was evaluated using 2,3,5-triphenyltetrazolium chloride staining, neurological deficit score, brain water content, hematoxylin and eosin staining, Nissl staining, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling staining. Immunofluorescence, immunohistochemistry, qRT-PCR, Western blot, and relative kits were used for detecting inflammatory factors, oxidative stress related factors, and mRNA and protein levels. The Cell Counting Kit-8 assay and flow cytometry were applied for assessing the viability and apoptosis of oxygen-glucose deprivation)/reoxygenation (OGD/R)-induced PC12 cells. OPD ameliorated brain injury via inhibiting neurons apoptosis, oxidative stress, and inflammatory response in cerebral infarction rats. In addition, we found that OPD attenuated the apoptosis, oxidative stress and inflammatory response in OGD/R-induced PC12 cells. Both in CIRI rats and OGD/R-induced PC12 cells, OPD was demonstrated to inhibit signal transducer and activator of transcription 3 (STAT3) phosphorylation. Moreover, Colivelin TFA (a STAT3 activator) reversed OPD effect on the apoptosis, oxidative stress, and inflammatory response in OGD/R-induced PC12 cells. Our findings demonstrated that OPD could protect against CIRI in rats by inhibiting STAT3 phosphorylation.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":"1-13"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156078","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":"A practical consideration for the substrate concentration when determining IC₅₀ values for enzyme inhibition.","authors":"Stephen L Bearne","doi":"10.1139/bcb-2025-0264","DOIUrl":"10.1139/bcb-2025-0264","url":null,"abstract":"<p><p>Determination of IC₅₀ values at a fixed substrate concentration ([S]) is frequently used to rank the potency of enzyme inhibitors and estimate inhibitor concentrations ([I]) to use in full inhibition analyses, particularly for structure-activity studies wherein the mode of inhibition is often known. Assays at an [S] yielding the greatest difference between the initial rates observed in the absence (<i>v</i>_o) and in the presence (<i>v</i>_i) of an inhibitor (i.e., <i>v</i>_o - <i>v</i>_i) will increase the sensitivity for the detection of enzyme inhibition. For noncompetitive and uncompetitive inhibitors of single-substrate enzymes, <i>v</i>_o - <i>v</i>_i increases with increasing [S]; however, for competitive and linear mixed-type (LMT) inhibitors, <i>v</i>_o - <i>v</i>_i obtains a maximum at a specific \"optimal\" substrate concentration ([S]_opt). Equations are derived describing the dependence of [S]_opt on [I], the dissociation constant for the inhibitor (<i>K</i>_i), and the Michaelis constant for the substrate (<i>K</i>_m). For example, for competitive inhibition, [S]_opt = <i>K</i>_m <math><msqrt><mn>1</mn> <mo>+</mo> <mfenced> <mrow> <mrow><mrow><mo>[</mo> <mi>I</mi> <mo>]</mo></mrow> <mo>/</mo> <mrow> <msub><mrow><mi>K</mi></mrow> <mrow><mi>i</mi></mrow> </msub> </mrow> </mrow> </mrow> </mfenced> </msqrt> </math> . For [I]/<i>K</i>_i values typically employed for inhibition studies (e.g., 0.5 ≤ [I]/<i>K</i>_i ≤ 4), [S] ≈ 2<i>K</i>_m or 3<i>K</i>_m will generally maximize the <i>v</i>_o - <i>v</i>_i difference for competitive or LMT (α ≥ 7) inhibitors, respectively. For competitive inhibition of bireactant enzymes, the \"optimal\" substrate concentrations depend on the Michaelis constants for both substrates, [I]/<i>K</i>_i, and the concentration of the second substrate.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":"1-10"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145342951","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":"Retraction: MicroRNA-24 alleviates isoflurane-induced neurotoxicity in rat hippocampus via attenuation of oxidative stress.","authors":"","doi":"10.1139/bcb-2025-0018","DOIUrl":"10.1139/bcb-2025-0018","url":null,"abstract":"","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":"103 ","pages":"1"},"PeriodicalIF":2.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143498114","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":"Doxorubicin, a DNA intercalator, inhibits transcription elongation.","authors":"Mathew Tempel, Kari Green, Dhanvi Prajapati, Angela Duaqui, Mahboobeh Norouzi, Hedieh Sattarifard, Ahmed Ashraf, Elly Wu, Athanasios Zovoilis, Ted M Lakowski, James R Davie","doi":"10.1139/bcb-2024-0264","DOIUrl":"10.1139/bcb-2024-0264","url":null,"abstract":"<p><p>Doxorubicin is a chemotherapeutic drug for cancer that intercalates into nucleosome-free regions at promoters. Doxorubicin was reported to result in loss of histone H3 trimethylated lysine 4 (H3K4me3). To further explore doxorubicin's mechanism of action, we determined the genomic location of the binding sites of doxorubicin in leukemic cells. The effect of doxorubicin intercalation into the chromatin of leukemic cells on histone modifications was also determined. We show that doxorubicin binding sites were present in the nucleosome-free regions associated with regulatory regions (promoters, enhancers, and super-enhancers) and in the gene body (introns). Doxorubicin treatment did not alter the levels of H3K4me3 and many other histone modifications but significantly lowered H2B ubiquitinated at lysine 120 (H2BK120ub), an elongation-dependent modification. Lastly, we demonstrate that doxorubicin results in the degradation of the largest subunit (RPB1) of RNA polymerase II.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":"1-12"},"PeriodicalIF":2.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416942","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":"Gallein, G protein βγ subunits inhibitor, suppresses the TGF-α-induced migration of hepatocellular carcinoma cells via inhibition of the c-<i>Jun</i> N-terminal kinase.","authors":"Rie Matsushima-Nishiwaki, Yoh Honda, Haruhiko Tokuda, Osamu Kozawa","doi":"10.1139/bcb-2024-0141","DOIUrl":"10.1139/bcb-2024-0141","url":null,"abstract":"<p><p>G protein-coupled receptor (GPCR) signaling regulates a wide range of pathophysiological cell functions via G protein α and βγ subunits. Small molecules targeting the subunits of Gα and Gβγ have been developed as cancer therapeutics. We have previously reported that transforming growth factor-α (TGF-α) induces the migration of human hepatocellular carcinoma (HCC) HuH7 cells through the activation of AKT, p38 mitogen-activated protein kinase (MAPK), Rho-kinase, and c-<i>Jun</i> N-terminal kinase (JNK). This study aims to determine whether Gβγ subunits regulate the TGF-α-induced migration of HCC HuH7 cells using gallein, a Gβγ subunits inhibitor. The Janus family of tyrosine kinase/signal transducer and activator of transcription 3 (STAT3) signaling pathway was also involved in the regulation of the migration. Gallein significantly reduced the TGF-α-induced cell migration. In contrast, fluorescein, a gallein-related compound that has no effect on Gβγ subunits, failed to affect the cell migration. Gallein suppressed the TGF-α-stimulated phosphorylation of JNK without affecting the phosphorylation of epidermal growth factor receptor, AKT, p38 MAPK, target protein of Rho-kinase, and STAT3. Conversely, fluorescein did not attenuate the phosphorylation of JNK. These results strongly suggest that Gβγ subunits act as positive regulators in TGF-α-induced migration of HCC cells via the JNK signaling pathway.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":"1-9"},"PeriodicalIF":2.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614083","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":"Retraction: PYGB facilitates cell proliferation and invasiveness in non-small cell lung cancer by activating the Wnt-β-catenin signaling pathway.","authors":"","doi":"10.1139/bcb-2025-0022","DOIUrl":"10.1139/bcb-2025-0022","url":null,"abstract":"","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":"103 ","pages":"1"},"PeriodicalIF":2.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522583","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":"Novel insights into RNA polymerase II transcription regulation: transcription factors, phase separation, and their roles in cardiovascular diseases.","authors":"Mengmeng Liu, Yingrui Li, Xin Yuan, Shunkang Rong, Jianlin Du","doi":"10.1139/bcb-2024-0094","DOIUrl":"10.1139/bcb-2024-0094","url":null,"abstract":"<p><p>Transcription factors (TFs) are specialized proteins that bind DNA in a sequence-specific manner and modulate RNA polymerase II (Pol II) in multiple steps of the transcription process. Phase separation is a spontaneous or driven process that can form membrane-less organelles called condensates. By creating different liquid phases at active transcription sites, the formation of transcription condensates can reduce the water content of the condensate and lower the dielectric constant in biological systems, which in turn alters the structure and function of proteins and nucleic acids in the condensate. In RNA Pol II transcription, phase separation formation shortens the time at which TFs bind to target DNA sites and promotes transcriptional bursting. RNA Pol II transcription is engaged in developing several diseases, such as cardiovascular disease, by regulating different TFs and mediating the occurrence of phase separation. This review aims to summarize the advances in the molecular mechanisms of RNA Pol II transcriptional regulation, in particular the effect of TFs and phase separation. The role of RNA Pol II transcriptional regulation in cardiovascular disease will be elucidated, providing potential therapeutic targets for the management and treatment of cardiovascular disease.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":"1-21"},"PeriodicalIF":2.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614125","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":"TRIM3 modulates cisplmatin-resistant of cervical squamous cell carcinoma via endoplasmic reticulum stress signaling in vitro.","authors":"Meiya Mao, Tianzi You, Kejun Xu, Huiqing Ding","doi":"10.1139/bcb-2024-0154","DOIUrl":"10.1139/bcb-2024-0154","url":null,"abstract":"<p><p>TRIM3 is widely recognized as a tumor suppressor gene. However, its precise role in cervical squamous cell carcinoma (CESC) remains elusive. Here, we observed a significant decrease in the expression of TRIM3 in CESC cells. Overexpression of TRIM3 suppresses cell proliferation and clonal formation. Through the establishment of cisplatin (cDDP)-resistant CESC cell lines, we discovered that the expression of TRIM3 was further downregulated in cDDP-resistant cells, while overexpression of TRIM3 enhanced cellular sensitivity to cDDP. Mechanistic investigations revealed that TRIM3 directly interacts with GRP78, a crucial protein involved in endoplasmic reticulum stress (ERS) pathway, promoting its ubiquitination degradation. Under cDDP treatment, the overexpression of TRIM3 in cDDP-resistant cells suppressed cell proliferation and downregulated the expression of drug-resistant genes, while simultaneously enhancing the activation of apoptosis signaling pathways. However, co-expression of TRIM3 and GRP78 restored cellular sensitivity to cDDP back to normal levels. Consequently, overexpressing TRIM3 in drug-resistant cells facilitates PERK activation and subsequent induction of apoptosis through inhibition of GRP78, ultimately suppressing drug resistance and inducing apoptosis in CESC cells. In conclution, our study suggests that the TRIM3/GRP78 axis regulates cDDP resistance in CESC cells by modulating the downstream apoptotic pathway of ERS.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":"1-12"},"PeriodicalIF":2.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766033","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}