{"title":"Autophagy Inhibition Increased Sensitivity of Pancreatic Cancer Cells to Carbon Ion Radiotherapy.","authors":"Makoto Sudo, Hiroko Tsutsui, Shuhei Hayashi, Koubun Yasuda, Keiko Mitani, Nana Iwami, Makoto Anzai, Toshiro Tsubouchi, Mitsuaki Ishida, Sohei Satoi, Tatsuaki Kanai, Seiko Hirono, Etsuro Hatano, Jiro Fujimoto","doi":"10.33594/000000639","DOIUrl":"10.33594/000000639","url":null,"abstract":"<p><strong>Background/aims: </strong>Pancreatic cancer has the poorest survival rate among all cancer types. Therefore, it is essential to develop an effective treatment strategy for this cancer.</p><p><strong>Methods: </strong>We performed carbon ion radiotherapy (CIRT) in human pancreatic cancer cell lines and analyzed their survival, apoptosis, necrosis, and autophagy. To investigate the role of CIRT-induced autophagy, autophagy inhibitors were added to cells prior to CIRT. To evaluate tumor formation, we inoculated CIRT-treated murine pancreatic cancer cells on the flank of syngeneic mice and measured tumor weight. We immunohistochemically measured autophagy levels in surgical sections from patients with pancreatic cancer who received neoadjuvant chemotherapy (NAC) plus CIRT or NAC alone.</p><p><strong>Results: </strong>CIRT reduced the survival fraction of pancreatic cancer cells and induced apoptotic and necrotic alterations, along with autophagy. Preincubation with an autophagy inhibitor accelerated cell death. Mice inoculated with control pancreatic cancer cells developed tumors, while those inoculated with CIRT/autophagy inhibitor-treated cells showed significant evasion. Surgical specimens of NAC-treated patients expressed autophagy comparable to control patients, while those in the NAC plus CIRT group expressed little autophagy and nuclear staining.</p><p><strong>Conclusion: </strong>CIRT effectively killed the pancreatic cancer cells by inhibiting their autophagy-inducing abilities.</p>","PeriodicalId":9845,"journal":{"name":"Cellular Physiology and Biochemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9841372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jolanta Guz, Ewelina Zarakowska, Pawel Mijewski, Aleksandra Wasilow, Justyna Szpotan, Marek Foksinski, Bartosz Brzoszczyk, Daniel Gackowski, Piotr Jarzemski, Ryszard Olinski
{"title":"Unprecedentedly High Level of Intracellular Vitamin C and DNA Epigenetic Marks in Prostate: Relevant for Male Fertility?","authors":"Jolanta Guz, Ewelina Zarakowska, Pawel Mijewski, Aleksandra Wasilow, Justyna Szpotan, Marek Foksinski, Bartosz Brzoszczyk, Daniel Gackowski, Piotr Jarzemski, Ryszard Olinski","doi":"10.33594/000000638","DOIUrl":"https://doi.org/10.33594/000000638","url":null,"abstract":"<p><strong>Background/aims: </strong>Seminal plasma composition is affected by the physiological state of the prostate, the major male reproductive gland. Semen components, like vitamin C, can modulate sperm function. Vitamin C is an effective scavenger of free radicals and is an essential component of enzymes such as TET proteins involved in the DNA demethylation process. In the present study, a broad range of parameters which may influence the metabolic state of the prostate gland were analysed including blood and prostate tissue vitamin C, epigenetic DNA modifications and 8-oxo-7,8-dihydro-2'-deoxyguanosine in DNA of leukocytes and prostate tissues.</p><p><strong>Methods: </strong>The experimental material were tissue samples from patients with benign prostatic hyperplasia (BPH), normal/marginal prostate tissues from prostate cancer patients, leukocytes from healthy donors, and blood plasma from BPH patients and healthy donors. We applied ultra-performance liquid chromatography methods with mass spectrometry and/or UV detection.</p><p><strong>Results: </strong>We found an unprecedentedly high level of intracellular vitamin C in all analysed prostatic tissues (benign prostatic hyperplasia and normal, marginal ones), a value much higher than in leukocytes and most human tissues. DNA epigenetic patterns in prostate cells are similar to other soft tissues like the colon, however, its uniqueness is the unprecedentedly high level of 5-(hydroxymethyl)-2'-deoxyuridine and a significant increase in 5-formyl-2'-deoxycytidine value compared to aforementioned tissues. Moreover, the level of 8-oxo-7,8-dihydro-2'-deoxyguanosine, an established marker of oxidative stress, is significantly higher in prostate tissues than in leukocytes and many previously studied soft tissues.</p><p><strong>Conclusion: </strong>Our results pointed out that prostatic vitamin C (regarded as the main supplier of the vitamin C to seminal plasma) and the DNA modifications (which may be linked to the regeneration of prostate epithelium) may play important role to maintain the prostate health.</p>","PeriodicalId":9845,"journal":{"name":"Cellular Physiology and Biochemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9834106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Role of O-GlcNAcylation in Breast Cancer Biology.","authors":"Karolina Kozal, Anna Krześlak","doi":"10.33594/000000633","DOIUrl":"https://doi.org/10.33594/000000633","url":null,"abstract":"<p><p>Breast cancer is the most common type of cancer in women. It has been extensively researched over the past decades, but the underlying mechanisms of its growth, proliferation, invasion, and metastasis require further investigation. Dysregulation of O-GlcNAcylation which is one of the most abundant post-translational modifications, impacts on the malignant features of breast cancer. O-GlcNAcylation is broadly recognized as a nutrient sensor and participates in cells' survival and death. Through its involvement in protein synthesis and energy metabolism, especially glucose metabolism, O-GlcNAcylation enables adaptation to a hostile environment. It supports the migration and invasion of cancer cells and may be crucial for breast cancer metastasis. This review summarizes the current state of knowledge about O-GlcNAcylation in breast cancer: the origins of its dysregulation, its effect on the different aspects of breast cancer biology, and the potential utility in diagnostics and therapy.</p>","PeriodicalId":9845,"journal":{"name":"Cellular Physiology and Biochemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9613809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vaibhav Gandhi, Ishan Wadi, T. Gupta, Divya Jindal, Pranav Pancham, Ashok Tiwari, S. Jha, R. Tiwari, Silpi Chanda, Chakresh Kumar, Jain, Manisha Singh
{"title":"A Model of Interaction Between Apocynin and NADPH Oxidase Enzyme to Analyze the Possible Targets Responsible for Inhibition by Computational Analysis","authors":"Vaibhav Gandhi, Ishan Wadi, T. Gupta, Divya Jindal, Pranav Pancham, Ashok Tiwari, S. Jha, R. Tiwari, Silpi Chanda, Chakresh Kumar, Jain, Manisha Singh","doi":"10.33594/000000632","DOIUrl":"https://doi.org/10.33594/000000632","url":null,"abstract":"Background/Aims: A multi-component enzyme system called NADPH oxidase (NOX) helps innate immunity by generating reactive oxygen species (ROS). NOX hyperactivation has been associated w several diseases. This enzyme is a membrane-bound complex made up of six subunits when it is active. These enzymatic subunits are considered to be potent inhibitors of enzyme activity and good targets for reducing oxidative stress. Methods: The present study aimed to analyze the possible targets: the different subunits of NOX, for their interactions with apocynin to identify its possible mechanism of inhibition for NOX, using in silico tools. Monomer, dimer, and trimer of apocynin were docked to various subunits of NOX. Results: Comparable glide scores were obtained when the monomer and dimer of apocynin were docked with p47phox complete subunit of NOX and were better than in comparison to trimer. Free Energy of Binding (FEB) was highest in the case of the trimer (-37.4 Kcal/mol), followed by the dimer (-21.2 Kcal/mol) and monomer (-18.2 Kcal/mol). Dimer obtained the highest glide score of 8.25 (FEB =-25.1 Kcal/mol) with p67phox-isoform 2. The PH domain of p47phox and the SH3 domain of p67phox have their own best binding energy with dimmer. While molecular docking with Rac-Zn-GD, P, dimer, and trimer have shown comparable FEB. The residues, on which the ligands were found to interact, were of major significance being present in those domains that vicinity to inhibit or activate the complex and are important for the protein structure and functioning. MDS studies have confirmed the findings that the Apocynin trimer molecule has superior stability and interactions with the enzyme complex. Conclusion: It can be concluded from the study that trimer and dimer have better interactions in terms of FEB with p67phox and p47phox, indicating the reported findings in the literature.","PeriodicalId":9845,"journal":{"name":"Cellular Physiology and Biochemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46003103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ricardo Aparecido Baptista Nucci, Victor Abou Nehmi Filho, Wilson Jacob-Filho, José Pinhata Otoch, Ana Flávia Marçal Pessoa
{"title":"Role of Nutritional Supplements on Gut-Muscle Axis Across Age: a Mini-Review.","authors":"Ricardo Aparecido Baptista Nucci, Victor Abou Nehmi Filho, Wilson Jacob-Filho, José Pinhata Otoch, Ana Flávia Marçal Pessoa","doi":"10.33594/000000628","DOIUrl":"https://doi.org/10.33594/000000628","url":null,"abstract":"<p><p>Sarcopenia is a progressive skeletal muscle disorder associated with aging, resulting in loss of muscle mass and function. It has been linked to inflammation, oxidative stress, insulin resistance, hormonal changes (i.e. alterations in the levels or activity of hormones which can occur due to a variety of factors, including aging, stress, disease, medication, and environmental factors), and impaired muscle satellite cell activation. The gut microbiome is also essential for muscle health, and supplements such as probiotics, prebiotics, protein, creatine, and betaalanine can support muscle growth and function while also promoting gut health. Chronic low-grade inflammation is a leading cause of sarcopenia, which can activate signaling pathways that lead to muscle wasting and reduce muscle protein synthesis. Insulin resistance, hormonal changes, and impaired muscle satellite cell activation contribute to sarcopenia, and high levels of fat mass also play a role in the pathogenesis of sarcopenia. Resistance exercise and dietary supplementation have been shown to be effective treatments for sarcopenia. In addition, a combination of resistance exercise and supplementation has been shown to have a more significant beneficial effect on anthropometric and muscle function parameters, leading to a decrease in sarcopenic state. Thus, understanding the relationship between the gut microbiome and muscle metabolism is crucial for developing new treatments for sarcopenia across age groups.</p>","PeriodicalId":9845,"journal":{"name":"Cellular Physiology and Biochemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9830250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Expression of Concern.","authors":"","doi":"10.33594/000000624","DOIUrl":"https://doi.org/10.33594/000000624","url":null,"abstract":"","PeriodicalId":9845,"journal":{"name":"Cellular Physiology and Biochemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9396645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Expression of Concern.","authors":"","doi":"10.33594/000000623","DOIUrl":"https://doi.org/10.33594/000000623","url":null,"abstract":"","PeriodicalId":9845,"journal":{"name":"Cellular Physiology and Biochemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9396647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Erratum.","authors":"","doi":"10.33594/000000625","DOIUrl":"https://doi.org/10.33594/000000625","url":null,"abstract":"","PeriodicalId":9845,"journal":{"name":"Cellular Physiology and Biochemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9743240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Erratum.","authors":"","doi":"10.33594/000000626","DOIUrl":"https://doi.org/10.33594/000000626","url":null,"abstract":"","PeriodicalId":9845,"journal":{"name":"Cellular Physiology and Biochemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9743243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Meera B Krishna, Betcy Susan Johnson, Madavan Vasudevan, Sathy M Pillai, Malini Laloraya
{"title":"miRNA-mRNA Network in PBMCs of PCOS Women Identifies Overactivated Stress-Activated Kinases.","authors":"Meera B Krishna, Betcy Susan Johnson, Madavan Vasudevan, Sathy M Pillai, Malini Laloraya","doi":"10.33594/000000622","DOIUrl":"https://doi.org/10.33594/000000622","url":null,"abstract":"<p><strong>Background/aims: </strong>Earlier studies have revealed the miRNAs and mRNAs involved in Polycystic Ovarian Syndrome (PCOS), but little is known about their regulatory networks.</p><p><strong>Methods: </strong>To address this issue, we applied a comprehensive miRNA, mRNA profiling approach in peripheral blood of PCOS patients. We identified 30 differential miRNAs and 3310 differential transcripts. A robust computational framework was created to integrate matched miRNA and mRNA expression profiles in PCOS using feed-forward loops.</p><p><strong>Results: </strong>The network consisted of differential miRNAs, transcription factors (TFs), and their common predicted target genes. The key network consisted of 14 non-orphan network clusters with 50 TF-gene pairs, 8 TF-TF pairs, 6 miRNA-TF pairs and 36 miRNA- gene pairs which were later dissected into 16 subclusters. Gene ontology annotations revealed that a host of signals (hormone, growth factors -EGF/ PDGF, thrombopoietin, oxidative stress and vitamin/nutrition) regulate MAPK signaling altering angiogenesis, JAK-STAT signaling, apoptosis, inflammatory and immune response and steroidogenesis in PCOS women.</p><p><strong>Conclusion: </strong>MAPK signaling is identified as the syndrome´s major dysregulated pathway. Our data imparts a robust foundation to expand the work and pave the way to focus efforts on p38MAPK targeted therapeutic strategies in PCOS.</p>","PeriodicalId":9845,"journal":{"name":"Cellular Physiology and Biochemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9387169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}