Luigi Rosa, Antimo Cutone, Giusi Ianiro, Piera Valenti, Rosalba Paesano
{"title":"Lactoferrin in the treatment of interstitial cystitis: a retrospective pilot study.","authors":"Luigi Rosa, Antimo Cutone, Giusi Ianiro, Piera Valenti, Rosalba Paesano","doi":"10.1139/bcb-2024-0036","DOIUrl":"10.1139/bcb-2024-0036","url":null,"abstract":"<p><p>Interstitial cystitis (IC), defined as a painful bladder syndrome (PBS), is a chronic condition that manifests itself as a suprapubic pain associated with an enhancing of frequency/urgency of urination, and for which there is no cure. Here, we present a retrospective pilot study on women affected from IC/PBS and treated with bovine lactoferrin (bLf). A total of 31 women, affected (20) or unaffected (11) from hereditary thrombophilia (HT), presented the median of 6 episodes of IC/PBS during the 6 months before the study. Treatment consisted of 17 weeks of orally administered Valpalf<sup>®</sup> capsules, containing bLf plus sodium bicarbonate and citrate. Out of 31 patients, only 3 women had one episode of IC/PBS during the follow-up period, while no episode was observed in 28 women. In the HT group, a significant decrease in both serum IL-6 and D-dimers was found after Valpalf<sup>®</sup> treatment. Moreover, in Valpalf<sup>®</sup>-treated women, cystoscopy revealed a global improvement in the appearance of the bladder, especially in term of inflammation/irritation and presence of Hunner ulcers. Even if our results must be corroborated by randomized double-blinded controlled trials on a larger number of patients, our observations indicate that bLf treatment is efficient in relieving IC/PBS symptoms, without side effects.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":"506-514"},"PeriodicalIF":2.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141874057","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}
Jihong Zhang, Lin Wang, Xi Zhang, Qiuli Sun, Junhe Zhang
{"title":"Matrix attachment regions enhance transgene expression by manipulating position-dependent effects in stably transfected CHO-K1 cells.","authors":"Jihong Zhang, Lin Wang, Xi Zhang, Qiuli Sun, Junhe Zhang","doi":"10.1139/bcb-2023-0337","DOIUrl":"10.1139/bcb-2023-0337","url":null,"abstract":"<p><p>We previously found that the position of matrix attachment regions (MARs) within the vector significantly affects its ability to enhance transgenic expression in the recombinant protein production. This study aims to systematically investigate the position-dependent impacts of MAR on transgene expression. We observed a significant increase in enhanced green fluorescent protein (eGFP) expression levels in stably transfected CHO-K1 cells with either MAR 1-68 or MAR X-29 when MARs located upstream of the promoter. This increase was especially evident with MAR flanked the expression cassette. Concurrently, a substantial increase was observed in the percentage of eGFP-expressing cells, with 97.8% and 96.0% in MAR-containing constructs versus 73.7% in MAR-absent constructs. Further analysis of erythropoietin (EPO) expression revealed that constructs with flanking MARs induced the highest EPO productivity. Bioinformatics analysis revealed that certain specific transcription factors are important in modulating the transcription process. In conclusion, vectors harboring both MARs around the expression cassette constitute an optimal construct for enhanced recombinant protein production in CHO-K1 cells. This insight underscores the importance of strategic MAR incorporation in vector design for optimized recombinant protein expression.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":"526-534"},"PeriodicalIF":2.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141726818","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-Jun N-terminal kinase.","authors":"Rie Matsushima-Nishiwaki, Yoh Honda, Haruhiko Tokuda, Osamu Kozawa","doi":"10.1139/bcb-2024-0141","DOIUrl":"https://doi.org/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-Jun 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 (JAK)/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 signalling pathway.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-11-13","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":"Interconnected roles of fungal nuclear- and intron-encoded maturases: at the crossroads of mitochondrial intron splicing.","authors":"Jigeesha Mukhopadhyay, Georg Hausner","doi":"10.1139/bcb-2024-0046","DOIUrl":"10.1139/bcb-2024-0046","url":null,"abstract":"<p><p>Group I and II introns are large catalytic RNAs (ribozymes) that are frequently encountered in fungal mitochondrial genomes. The discovery of respiratory mutants linked to intron splicing defects demonstrated that for the efficient removal of organellar introns there appears to be a requirement of protein splicing factors. These splicing factors can be intron-encoded proteins with maturase activities that usually promote the splicing of the introns that encode them (<i>cis</i>-acting) and/or nuclear-encoded factors that can promote the splicing of a range of different introns (<i>trans</i>-acting). Compared to plants organellar introns, fungal mitochondrial intron splicing is still poorly explored, especially in terms of the synergy of nuclear factors with intron-encoded maturases that has direct impact on splicing through their association with intron RNA. In addition, nuclear-encoded accessory factors might drive the splicing impetus through translational activation, mitoribosome assembly, and phosphorylation-mediated RNA turnover. This review explores protein-assisted splicing of introns by nuclear and mitochondrial-encoded maturases as a means of mitonuclear interplay that could respond to environmental and developmental factors promoting phenotypic adaptation and potentially speciation. It also highlights key evolutionary events that have led to changes in structure and ATP-dependence to accommodate the dual functionality of nuclear and organellar splicing factors.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":"351-372"},"PeriodicalIF":2.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141247167","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}
Mimi Mu, Gao Liu, Xiaoyu Ding, Lijun Xue, Dandan Li, Yunhua Zhu, Nan Zhang, Jia Wu, Junjun Wang
{"title":"miR-520e and its promoter region DNA methylation as potential biomarkers in atherosclerosis.","authors":"Mimi Mu, Gao Liu, Xiaoyu Ding, Lijun Xue, Dandan Li, Yunhua Zhu, Nan Zhang, Jia Wu, Junjun Wang","doi":"10.1139/bcb-2023-0326","DOIUrl":"10.1139/bcb-2023-0326","url":null,"abstract":"<p><p>In atherosclerosis, DNA methylation plays a key regulatory role in the expression of related genes. However, the molecular mechanisms of these processes in human umbilical vein endothelial cells (HUVECs) are unclear. Here, using high-throughput sequencing from the Infinium HumanMethylation450 assay, we manifested that the cg19564375 methylation of miR-520e promoter region in the peripheral blood of acute coronary syndrome (ACS) patients was higher than that of healthy controls. As shown by RQ-MSP, the upstream DNA methylation level of the miR-520e promoter region was considerably increased in ACS patients. miR-520e was markedly downregulated in ACS patients compared with healthy controls. In the oxidized low-density lipoprotein (ox-LDL)-induced HUVECs injury model, DNA methylation of the upstream region of miR-520e was significantly increased. With increasing concentrations of the methylase inhibitor 5-Aza, miR-520e expression was upregulated. The silence of methyltransferase DNMT1, rather than DNMT3a or DNMT3b, abolished the influence of miR-520e expression by ox-LDL treatment in HUVECs. A dual luciferase reporter assay revealed that miR-520e regulated the TGFBR2 3'-untranslated region region. After silencing TGFBR2, the promoting effect of miR-520e inhibitor on cell proliferation and migration may be attenuated. In conclusion, the expression of miR-520e is modified by its promoter region DNA methylation, and miR-520e and its promoter region DNA methylation may be potential biomarkers in atherosclerosis.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":"385-393"},"PeriodicalIF":2.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141449559","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}
Sampurna Ghosh, Sk Eashayan Tanbir, Tulika Mitra, Sib Sankar Roy
{"title":"Unveiling stem-like traits and chemoresistance mechanisms in ovarian cancer cells through the TGFβ1-PITX2A/B signaling axis.","authors":"Sampurna Ghosh, Sk Eashayan Tanbir, Tulika Mitra, Sib Sankar Roy","doi":"10.1139/bcb-2024-0010","DOIUrl":"10.1139/bcb-2024-0010","url":null,"abstract":"<p><p>Ovarian cancer (OC) is the deadliest gynecological malignancy, having a high mortality rate due to its asymptomatic nature, chemoresistance, and recurrence. However, the proper mechanistic knowledge behind these phenomena is still inadequate. Cancer recurrence is commonly observed due to cancer stem cells which also show chemoresistance. We aimed to decipher the molecular mechanism behind chemoresistance and stemness in OC. Earlier studies suggested that PITX2, a homeobox transcription factor and, its different isoforms are associated with OC progression upon regulating different signaling pathways. Moreover, they regulate the expression of drug efflux transporters in kidney and colon cancer, rendering chemoresistance properties in the tumor cell. Considering these backgrounds, we decided to look for the role of PITX2 isoforms in promoting stemness and chemoresistance in OC cells. In this study, PITX2A/B has been shown to promote stemness and to enhance the transcription of ABCB1. PITX2 has been discovered to augment ABCB1 gene expression by directly binding to its promoter. To further investigate the regulatory mechanism of PITX2 gene expression, we found that TGFβ signaling could augment the PITX2A/B expression through both SMAD and non-SMAD signaling pathways. Collectively, we conclude that TGFβ1-activated PITX2A/B induces stem-like features and chemoresistance properties in the OC cells.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":"394-409"},"PeriodicalIF":2.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141557899","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}
Grace Martin, Dhuha Al-Sajee, Molly Gingrich, Rimsha Chattha, Michael Akcan, Cynthia M F Monaco, Megan C Hughes, Christopher G R Perry, Irena A Rebalka, Mark A Tarnopolsky, Thomas J Hawke
{"title":"Skeletal muscle mitochondrial morphology negatively affected in mice lacking Xin.","authors":"Grace Martin, Dhuha Al-Sajee, Molly Gingrich, Rimsha Chattha, Michael Akcan, Cynthia M F Monaco, Megan C Hughes, Christopher G R Perry, Irena A Rebalka, Mark A Tarnopolsky, Thomas J Hawke","doi":"10.1139/bcb-2024-0034","DOIUrl":"10.1139/bcb-2024-0034","url":null,"abstract":"<p><p>Altered mitochondrial structure and function are implicated in the functional decline of skeletal muscle. Numerous cytoskeletal proteins are known to affect mitochondrial homeostasis, but this complex network is still being unraveled. Here, we investigated mitochondrial alterations in mice lacking the cytoskeletal adapter protein, XIN (XIN-/-). XIN-/- and wild-type littermate male and female mice were fed a chow or high-fat diet (HFD; 60% kcal fat) for 8 weeks before analyses of their skeletal muscles were conducted. Immuno-electron microscopy (EM) and immunofluorescence staining revealed XIN in the mitochondria and peri-mitochondrial areas, as well as the myoplasm. Intermyofibrillar mitochondria in chow-fed XIN-/- mice were notably different from wild-type (large, and/or swollen in appearance). Succinate dehydrogenase and Cytochrome Oxidase IV staining indicated greater evidence of mitochondrial enzyme activity in XIN-/- mice. No difference in body mass gains or glucose handling was observed between cohorts with HFD. However, EM revealed significantly greater mitochondrial density with evident structural abnormalities (swelling, reduced cristae density) in XIN-/- mice. Absolute Complex I and II-supported respiration was not different between groups, but relative to mitochondrial density, was significantly lower in XIN-/-. These results provide the first evidence for a role of XIN in maintaining mitochondrial morphology and function.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":"373-384"},"PeriodicalIF":2.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141282912","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}
Giuditta Pollio, Luigi Rosa, Anna Maria Costanzo, Rosalba Paesano, Giovanni Tripepi, Piera Valenti
{"title":"Lactoferrin efficacy in treating hyperferritinemia in patients suffering from pathologies unrelated to hereditary hemochromatosis.","authors":"Giuditta Pollio, Luigi Rosa, Anna Maria Costanzo, Rosalba Paesano, Giovanni Tripepi, Piera Valenti","doi":"10.1139/bcb-2024-0061","DOIUrl":"10.1139/bcb-2024-0061","url":null,"abstract":"<p><p>Ferritin (Ftn), a globular protein, sequesters 4500 atoms of iron per molecule. Elevated serum Ftn levels (hyperferritinemia) is an indicator of iron homeostasis disorders. We present the results of an observational study involving 17 patients with hyperferritinemia unrelated to hereditary hemochromatosis (HH). All participants received treatment with 200 mg of bovine lactoferrin (bLf) once (<i>n</i> = 14) or twice (<i>n</i> = 3) a day before meals. The patients, treated with 200 mg/day of bLf, exhibited a significant increase in red blood cells (+10%, <i>p</i> < 0.001), hemoglobin (+4%, <i>p</i> < 0.001), and hematocrit (+15%, <i>p</i> = 0.004), accompanied by a significant reduction in serum Ftn levels (-52%, <i>p</i> < 0.001), C-reactive protein (CRP) (-85.0%, <i>p</i> < 0.001), and D-dimers (-19%, <i>p</i> < 0.001). Among the three patients treated with 400 mg/day of bLf, two had effects similar to those of patients bLf-treated with 200 mg/day and one experienced a strong reduction of Ftn, CRP, and erythrocyte sedimentation rate (from -97% to -75%). The decrease in serum Ftn levels due to bLf treatment was largely independent of gender (<i>p</i> = 0.78), age (<i>p</i> = 0.66), baseline symptoms (<i>p</i> = 0.20), and concomitant acute (<i>p</i> = 0.34) and chronic (<i>p</i> = 0.53) infections. Although this observational pilot study yields positive effects in patients with hyperferritinemia unrelated to HH treated with bLf, a larger sample size is needed for conclusive results.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":"410-417"},"PeriodicalIF":2.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141562566","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":"20 years of choices: a fight for increased funding for graduate students.","authors":"Fabian Rohden, Thomas Bailey, Sarah Laframboise","doi":"10.1139/bcb-2024-0029","DOIUrl":"10.1139/bcb-2024-0029","url":null,"abstract":"<p><p>After 20 years of stagnation, federal scholarships have finally been increased within the new budget of the Canadian government. Tuition fees, inflation, and costs of living kept rising, which has resulted a rising number of graduate students in the life sciences living below poverty line, despite working far more than 40 h a week on science research in Canada. This does not only negatively affect the students research projects and thus science and innovation in Canada, but also their downstream decisions on whether to continue a research career in Canada and what jobs and economic endeavors to pursue. Graduate students are not just a line item in the budgets of universities, but integral for science and innovation, as well as the future high-quality personnel of the country. This importance should be reflected in all stipends and salaries of graduate students, not just the ones with a government scholarship.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":"346-350"},"PeriodicalIF":2.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142071857","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}
Ashraf K Shahib,Mojgan Rastegar,Andre J van Wijnen,James R Davie
{"title":"Neurodevelopmental functions and activities of the KAT3 class of lysine acetyltransferases.","authors":"Ashraf K Shahib,Mojgan Rastegar,Andre J van Wijnen,James R Davie","doi":"10.1139/bcb-2024-0156","DOIUrl":"https://doi.org/10.1139/bcb-2024-0156","url":null,"abstract":"The human lysine acetyltransferases KAT3A (CREBBP) and KAT3B (EP300) are essential enzymes in gene regulation in the nucleus. Their ubiquitous expression in metazoan cell types controls cell proliferation and differentiation during development. This comprehensive review delves into the biological roles of KAT3A and KAT3B in neurodevelopment, shedding light on how alterations in their regulation or activity can potentially contribute to a spectrum of neurodegenerative diseases (e.g. Huntington's and Alzheimer's). We explore the pathophysiological implications of KAT3 function loss in these disorders, considering their conserved protein domains and biochemical functions in chromatin regulation. The discussion also underscores the crucial role of KAT3 proteins and their substrates in supporting the integration of key cell signaling pathways. Furthermore, the narrative highlights the interdependence of KAT3-mediated lysine acetylation with lysine methylation and arginine methylation. From a cellular perspective, KAT3-dependent signal integration at subnuclear domains is mediated by liquid-liquid phase separation in response to KAT3-mediated lysine acetylation. The disruption of these finely tuned regulatory processes underscores their pathological roles in neurodegeneration. This review also points to the exciting potential for future research in this field, inspiring further investigation and discovery in the area of neurodevelopment and neurodegenerative diseases.","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":"12 8 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142255908","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}