{"title":"LINE-1: an emerging initiator of cGAS-STING signalling and inflammation that is dysregulated in disease.","authors":"Sabateeshan Mathavarajah, Graham Dellaire","doi":"10.1139/bcb-2023-0134","DOIUrl":"10.1139/bcb-2023-0134","url":null,"abstract":"<p><p>The cGAS-STING (cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING)) axis integrates DNA damage and cellular stress with type I interferon (IFN) signalling to facilitate transcriptional changes underlying inflammatory stress responses. The cGAS-STING pathway responds to cytosolic DNA in the form of double-stranded DNA, micronuclei, and long interspersed nuclear element 1 (L1) retroelements. L1 retroelements are a class of self-propagating non-long terminal repeat transposons that have remained highly active in mammalian genomes. L1 retroelements are emerging as important inducers of cGAS-STING and IFN signalling, which are often dysregulated in several diseases, including cancer. A key repressor of cGAS-STING and L1 activity is the exonuclease three prime repair exonuclease 1 (TREX1), and loss of TREX1 promotes the accumulation of L1. In addition, L1 dysregulation is a common theme among diseases with chronic induction of type I IFN signalling through cGAS-STING, such as Aicardi-Goutières syndrome, Fanconi anemia, and dermatomyositis. Although TREX1 is highly conserved in tetrapod species, other suppressor proteins exist that inhibit L1 retrotransposition. These suppressor genes when mutated are often associated with diseases characterized by unchecked inflammation that is associated with high cGAS-STING activity and elevated levels of L1 expression. In this review, we discuss these interconnected pathways of L1 suppression and their role in the regulation of cGAS-STING and inflammation in disease.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":"38-46"},"PeriodicalIF":2.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10103733","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}
Aleksandra Majewska, Klaudia Brodaczewska, Aleksandra Filipiak-Duliban, Claudine Kieda
{"title":"Comparative analysis of the effect of hypoxia in two different tumor cell models shows the differential involvement of PTEN control of proangiogenic pathways.","authors":"Aleksandra Majewska, Klaudia Brodaczewska, Aleksandra Filipiak-Duliban, Claudine Kieda","doi":"10.1139/bcb-2023-0047","DOIUrl":"10.1139/bcb-2023-0047","url":null,"abstract":"<p><p>Hypoxia, low, non-physiological oxygen tension is a key regulator of tumor microenvironment, determining the pathological tumor vascularization. Alleviation of hypoxia through vessel normalization may be a promising therapeutic approach. We aimed to assess the role of low oxygen tension in PTEN-related pathways and proangiogenic response, in vitro, in two different tumor cell lines, focusing on potential therapeutic targets for tumor vessel normalization. Downregulation of PTEN in hypoxia mediates the activation of distinct mechanisms: cytoplasmic pAKT activation in melanoma and pMDM2 modulation in kidney cancer. We show that hypoxia-induced proangiogenic potential was stronger in Renca cells than B16 F10-confirmed by a distinct secretory potential and different ability to affect endothelial cells functions. Therefore, the impact of hypoxia on PTEN-mediated regulation may determine the therapeutic targets and effectiveness of vessel normalization and intrinsic characteristics of cancer cell have to be taken into account when designing treatment.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":"47-59"},"PeriodicalIF":2.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10474933","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}
Caroline M Putnam, Lahari Kondeti, Meredith B A Kesler, Melinda E Varney
{"title":"Modulating the immune system as a therapeutic target for myelodysplastic syndromes and acute myeloid leukemia.","authors":"Caroline M Putnam, Lahari Kondeti, Meredith B A Kesler, Melinda E Varney","doi":"10.1139/bcb-2022-0374","DOIUrl":"10.1139/bcb-2022-0374","url":null,"abstract":"<p><p>Modulating the immune system to treat diseases, including myeloid malignancies, has resulted in the development of a multitude of novel therapeutics in recent years. Myelodysplastic syndromes or neoplasms (MDS) and acute myeloid leukemia (AML) are hematologic malignancies that arise from defects in hematopoietic stem and progenitor cells (HSPCs). Dysregulated immune responses, especially in innate immune and inflammatory pathways, are highly associated with the acquisition of HSPC defects in MDS and AML pathogenesis. In addition to utilizing the immune system in immunotherapeutic interventions such as chimeric antigen receptor T cell therapy, vaccines, and immune checkpoint inhibitors, mitigating dysregulation of innate immune and inflammatory responses in MDS and AML remains a priority in slowing the initiation and progression of these myeloid malignancies. This review provides a comprehensive summary of the current progress of diverse strategies to utilize or modulate the immune system in the treatment of MDS and AML.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":"481-495"},"PeriodicalIF":2.9,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9979226","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":"Time to treat the climate and nature crisis as one indivisible global health emergency.","authors":"","doi":"10.1139/bcb-2023-0329","DOIUrl":"10.1139/bcb-2023-0329","url":null,"abstract":"","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":"101 6","pages":"i-iii"},"PeriodicalIF":2.9,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138497716","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":"NDUFA4 promotes the progression of head and neck paraganglioma by inhibiting ferroptosis.","authors":"Zhigang Wang, Erxing Tao, Yiming Chen, Qi Wang, Min Liu, Liang Wei, Siyi Xu, Wei Chen, Chunlong Zhong","doi":"10.1139/bcb-2023-0018","DOIUrl":"10.1139/bcb-2023-0018","url":null,"abstract":"<p><p>NDUFA4 is a component of respiratory chain-oxidative phosphorylation pathway. NDUFA4 is highly expressed in tumor tissues, but little is known about the function of NDUFA4 in head and neck paraganglioma (HNPGL). We examined NDUFA4 expression in tissues from 10 HNPGL patients and 6 controls using qRT-PCR and Western blotting. NDUFA4 knockdown PGL-626 cells were established by using lentivirus infection and puromycin screening. Cell viability, ATP production, lipid reactive oxygen species, and mitochondrial membrane potential assays were performed to investigate the ferroptotic effects in NDUFA4 deficiency HNPGL cancer cells. Xenograft mouse model was created to detect the synergetic antitumor action between NDUFA4 deficiency and Metformin. NDUFA4 was upregulated in tumor tissues of HNPGL patients. NDUFA4 knockdown impaired the assembly of mitochondrial respiratory chain complexes and decreased the production of ATP and reduced cancer cell viability. Mechanistically, NDUFA4 knockdown increased cell ferroptosis, which further promoted Metformin-induced ferroptosis in PGL-626 cells. Therefore, NDUFA4 deficiency enhanced Metformin-mediated inhibition of the HNPGL progression in mice. In conclusion, NDUFA4 promotes the progression of HNPGL, and NDUFA4 knockdown enhances Metformin-mediated inhibition of the HNPGL progression in a mouse model.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":"523-530"},"PeriodicalIF":2.9,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10022465","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}
Johan Sebastian Lopez Salguero, Melissa Rodríguez Rendón, Jessica Triviño Valencia, Jorge Andrés Cuellar Gil, Carlos Andrés Naranjo Galvis, Oscar Moscoso Londoño, César Leandro Londoño Calderón, Fabio Augusto Gonzáles Osorio, Reinel Tabares Soto
{"title":"Automatic detection of <i>Cryptosporidium</i> in optical microscopy images using YOLOv5<i>x</i>: a comparative study.","authors":"Johan Sebastian Lopez Salguero, Melissa Rodríguez Rendón, Jessica Triviño Valencia, Jorge Andrés Cuellar Gil, Carlos Andrés Naranjo Galvis, Oscar Moscoso Londoño, César Leandro Londoño Calderón, Fabio Augusto Gonzáles Osorio, Reinel Tabares Soto","doi":"10.1139/bcb-2023-0059","DOIUrl":"10.1139/bcb-2023-0059","url":null,"abstract":"<p><p>Here, a machine learning tool (YOLOv5) enables the detection of <i>Cryptosporidium</i> microorganisms using optical and phase contrast microscope images. The two databases were processed using 520 images (optical microscopy) and 1200 images (phase contrast microscopy). It used Python libraries to label, standardize the size, and crop the images to generate the input tensors to the YOLOv5 network (s, m, and l). It implemented two experiments using randomly initialized weights in optical and phase contrast microscope images. The other two experiments used the parameters for the best training time obtained before and after retraining the models. Metrics used to assess model accuracy were mean average accuracy, confusion matrix, and the F1 scores. All three metrics confirmed that the optimal model used the best epoch of optical imaging training and retraining with phase contrast imaging. Experiments with randomly initialized weights with optical imaging showed the lowest precision for <i>Cryptosporidium</i> detection. The most stable model was YOLOv5m, with the best results in all categories. However, the differences between all models are lower than 2%, and YOLOv5s is the best option for <i>Cryptosporidium</i> detection considering the differences in computational costs of the models.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":"538-549"},"PeriodicalIF":2.9,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10367400","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":"18th International Conference of Biochemistry & Molecular Biology (18th ICBMB)","authors":"","doi":"10.1139/bcb-2023-0300","DOIUrl":"https://doi.org/10.1139/bcb-2023-0300","url":null,"abstract":"","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":"8 19","pages":""},"PeriodicalIF":2.9,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138625402","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":"The effects of cetuximab and cisplatin anti-cancer drugs on the mechanical properties of the lung cancerous cells using atomic force microscope.","authors":"Iraj Rezaei, Ali Sadeghi","doi":"10.1139/bcb-2022-0322","DOIUrl":"10.1139/bcb-2022-0322","url":null,"abstract":"<p><p>Each anti-cancer drug has special effects on the target cells. One of the most important reasons to recommend an anti-cancer drug is related to the influences of it on the mechanical properties of the target cells. In this study, the effects of cetuximab and cisplatin anti-cancer drugs on the mechanical properties of A-549 and Calu-6 cells as the cancerous lung cells have been investigated. For both of the cells and anti-cancer drugs, MTT assessment has been used to define the convenient dosages for 24 and 48 h incubations based on IC50 concentration for the cell line viability. The mechanical specifications of the cells before and after treatment were obtained using nanoindentation by the JPK Instruments' NanoWizard3 atomic force microscope. The results show that cetuximab increases the stiffness of A-549 cell from 1225 to 3403 and 12 690 Pa for 24 and 48 h incubations. The influence of cetuximab on the Calu-6 shows that the elastic modulus after 24 and 48 h culture times increases about cisplatin anti-cancer drug, for A-549 cell indicates that the elastic modulus rises from 1225 to 1506 and 2375 Pa for 24 and 48 h, respectively. For Calu-6 cell, cisplatin has an important role to increase the stiffness of the cell. Applying cisplatin increases the elastic modulus from 33 to 682.8 Pa for 24 h and 1105 Pa after 48 h incubations.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":"531-537"},"PeriodicalIF":2.9,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10357425","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}
Pablo A Iglesias González, Ángel G Valdivieso, Tomás A Santa-Coloma
{"title":"The G protein-coupled receptor GPRC5A-a phorbol ester and retinoic acid-induced orphan receptor with roles in cancer, inflammation, and immunity.","authors":"Pablo A Iglesias González, Ángel G Valdivieso, Tomás A Santa-Coloma","doi":"10.1139/bcb-2022-0352","DOIUrl":"10.1139/bcb-2022-0352","url":null,"abstract":"<p><p>GPRC5A is the first member of a new class of orphan receptors coupled to G proteins, which also includes GPRC5B, GPRC5C, and GPRC5D. Since its cloning and identification in the 1990s, substantial progress has been made in understanding the possible functions of this receptor. <i>GPRC5A</i> has been implicated in a variety of cellular events, such as cytoskeleton reorganization, cell proliferation, cell cycle regulation, migration, and survival. It appears to be a central player in different pathological processes, including tumorigenesis, inflammation, immune response, and tissue damage. The levels of <i>GPRC5A</i> expression differ depending on the type of cancer, with increased expression in colon, pancreas, and prostate cancers; decreased expression in lung cancer; and varied results in breast cancer. In this review, we discuss the early discovery of <i>GPRC5A</i> as a phorbol ester-induced gene and later as a retinoic acid-induced gene, its regulation, and its participation in important canonical pathways related to numerous types of tumors and inflammatory processes. <i>GPRC5A</i> represents a potential new target for cancer, inflammation, and immunity therapies.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":"465-480"},"PeriodicalIF":2.9,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10167104","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}