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Correction: NCAPD2 is a favorable predictor of prognostic and immunotherapeutic biomarker for multiple cancer types including lung cancer. 更正:NCAPD2 是包括肺癌在内的多种癌症类型的预后和免疫治疗生物标志物。
IF 1.7 4区 医学
Genes and Environment Pub Date : 2024-02-13 DOI: 10.1186/s41021-024-00301-z
Linyuan Feng, Yang Yang, Zhenhua Lin, Minghua Cui, Aihua Jin, Aili Cui
{"title":"Correction: NCAPD2 is a favorable predictor of prognostic and immunotherapeutic biomarker for multiple cancer types including lung cancer.","authors":"Linyuan Feng, Yang Yang, Zhenhua Lin, Minghua Cui, Aihua Jin, Aili Cui","doi":"10.1186/s41021-024-00301-z","DOIUrl":"10.1186/s41021-024-00301-z","url":null,"abstract":"","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":"46 1","pages":"6"},"PeriodicalIF":1.7,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10863280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139722284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Understanding exposomes and its relation with cancer risk in Malaysia based on epidemiological evidence: a narrative review. 根据流行病学证据了解马来西亚的暴露体及其与癌症风险的关系:叙述性综述。
IF 1.7 4区 医学
Genes and Environment Pub Date : 2024-02-08 DOI: 10.1186/s41021-024-00300-0
Razinah Sharif, Theng Choon Ooi
{"title":"Understanding exposomes and its relation with cancer risk in Malaysia based on epidemiological evidence: a narrative review.","authors":"Razinah Sharif, Theng Choon Ooi","doi":"10.1186/s41021-024-00300-0","DOIUrl":"10.1186/s41021-024-00300-0","url":null,"abstract":"<p><p>The prevalence of cancer is increasing globally, and Malaysia is no exception. The exposome represents a paradigm shift in cancer research, emphasizing the importance of a holistic approach that considers the cumulative effect of diverse exposures encountered throughout life. The exposures include dietary factors, air and water pollutants, occupational hazards, lifestyle choices, infectious agents and social determinants of health. The exposome concept acknowledges that each individual's cancer risk is shaped by not only their genetic makeup but also their unique life experiences and environmental interactions. This comprehensive review was conducted by systematically searching scientific databases such as PubMed, Scopus and Google Scholar, by using the keywords \"exposomes (environmental exposures AND/OR physical exposures AND/OR chemical exposures) AND cancer risk AND Malaysia\", for relevant articles published between 2010 and 2023. Articles addressing the relationship between exposomes and cancer risk in the Malaysian population were critically evaluated and summarized. This review aims to provide an update on the epidemiological evidence linking exposomes with cancer risk in Malaysia. This review will provide an update for current findings and research in Malaysia related to identified exposomes-omics interaction and gap in research area related to the subject matter. Understanding the interplay between complex exposomes and carcinogenesis holds the potential to unveil novel preventive strategies that may be beneficial for public health.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":"46 1","pages":"5"},"PeriodicalIF":1.7,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10851543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139702292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Curcumin piperidone derivatives induce caspase-dependent apoptosis and suppress miRNA-21 expression in LN-18 human glioblastoma cells. 姜黄素哌啶酮衍生物可诱导 LN-18 人胶质母细胞瘤细胞发生依赖于 Caspase 的凋亡,并抑制 miRNA-21 的表达。
IF 1.7 4区 医学
Genes and Environment Pub Date : 2024-02-01 DOI: 10.1186/s41021-023-00297-y
Nur Syahirah Che Razali, Kok Wai Lam, Nor Fadilah Rajab, A Rahman A Jamal, Nurul Farahana Kamaludin, Kok Meng Chan
{"title":"Curcumin piperidone derivatives induce caspase-dependent apoptosis and suppress miRNA-21 expression in LN-18 human glioblastoma cells.","authors":"Nur Syahirah Che Razali, Kok Wai Lam, Nor Fadilah Rajab, A Rahman A Jamal, Nurul Farahana Kamaludin, Kok Meng Chan","doi":"10.1186/s41021-023-00297-y","DOIUrl":"10.1186/s41021-023-00297-y","url":null,"abstract":"<p><strong>Background: </strong>Previously, we have reported on the two curcuminoid analogues with piperidone derivatives, namely FLDP-5 and FLDP-8 have more potent anti-proliferative and anti-migration effects than curcumin. In this study, we further investigated the mode of cell death and the mechanism involved in the cell death process induced by these analogues on human glioblastoma LN-18 cells.</p><p><strong>Results: </strong>The FLDP-5 and FLDP-8 curcuminoid analogues induced LN-18 cell death through apoptosis in a concentration-dependent manner following 24 h of treatment. These analogues induced apoptosis in LN-18 cells through significant loss of mitochondrial mass and mitochondrial membrane potential (MMP) as early as 1-hour of treatment. Interestingly, N-acetyl-l-cysteine (NAC) pretreatment did not abolish the apoptosis induced by these analogues, further confirming the cell death process is independent of ROS. However, the apoptosis induced by the analogues is caspases-dependent, whereby pan-caspase pretreatment inhibited the curcuminoid analogues-induced apoptosis. The apoptotic cell death progressed with the activation of both caspase-8 and caspase-9, which eventually led to the activation of caspase-3, as confirmed by immunoblotting. Moreover, the existing over-expression of miRNA-21 in LN-18 cells was suppressed following treatment with both analogues, which suggested the down-regulation of the miRNA-21 facilitates the cell death process.</p><p><strong>Conclusion: </strong>The FLDP-5 and FLDP-8 curcuminoid analogues downregulate the miRNA-21 expression and induce extrinsic and intrinsic apoptotic pathways in LN-18 cells.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":"46 1","pages":"4"},"PeriodicalIF":1.7,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10832295/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139671558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
CDK4/6 inhibitor-induced bone marrow micronuclei might be caused by cell cycle arrest during erythropoiesis. CDK4/6 抑制剂诱导的骨髓微核可能是红细胞生成过程中细胞周期停滞所致。
IF 1.7 4区 医学
Genes and Environment Pub Date : 2024-02-01 DOI: 10.1186/s41021-024-00298-5
Yuki Okada, Satsuki Chikura, Takafumi Kimoto, Takeshi Iijima
{"title":"CDK4/6 inhibitor-induced bone marrow micronuclei might be caused by cell cycle arrest during erythropoiesis.","authors":"Yuki Okada, Satsuki Chikura, Takafumi Kimoto, Takeshi Iijima","doi":"10.1186/s41021-024-00298-5","DOIUrl":"10.1186/s41021-024-00298-5","url":null,"abstract":"<p><strong>Background: </strong>A micronucleus test is generally used to evaluate the genotoxic potential of chemicals. Exaggerated erythropoiesis, as occurs following bleeding, may induce an unexpected increase in micronucleus frequency. This false positive result would be typical in a genotoxicity study due to the enhanced progression of the cell cycle that restores decreased blood cells. The cyclin-dependent kinase (CDK) family is known to play an essential role in preventing genomic instability. Conversely, a selective CDK4/6 inhibitor PD0332991, clinically named Palbociclib, is reported to have genotoxic potential, shown by positive results in both in vitro and in vivo micronucleus studies. To clarify the mechanism by which cell cycle arrest induced by a CDK4/6 inhibitor increases micronucleus frequency, we investigated the positive results of the bone marrow micronucleus test conducted with PD0332991.</p><p><strong>Results: </strong>Rats treated with PD0332991 exhibited increased micronucleus frequency in an in vivo bone marrow micronucleus test whereas it was not increased by treatment in human lymphoblastoid TK6 cells. In addition, all other genotoxicity tests including the Ames test and the comet assay showed negative results with PD0332991. Interestingly, PD0332991 treatment led to an increase in erythrocyte size in rats and affected the size distribution of erythrocytes, including the micronucleus. The mean corpuscular volume of reticulocytes (MCVr) in the PD0332991 treatment group was significantly increased compared to that of the vehicle control (83.8 fL in the PD0332991, and 71.6 fL in the vehicle control.). Further, the average micronucleated erythrocytes (MNE) size of the PD0332991 group and vehicle control was 8.2 and 7.3 µm, respectively. In the histogram, the vehicle control showed a monomodal distribution with a peak near 7.3 µm. In contrast, the PD0332991 group showed a bimodal distribution with peaks around 7.5 and 8.5 µm. Micronucleated erythrocytes in the PD0332991 group were significantly larger than those in the vehicle control. These results suggest that the increase in micronucleus frequency induced by the CDK4/6 inhibitor is not due to genotoxicity, but is attributable to disturbance of the cell cycle, differentiation, and enucleation of erythroblasts.</p><p><strong>Conclusions: </strong>It was suggested that the positive outcome of the in vivo bone marrow micronucleus test resulting from treatment with PD0332991 could not be attributed to its genotoxicity. Further studies to clarify the mechanism of action can contribute to the development of drug candidate compounds lacking intrinsic genotoxic effects.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":"46 1","pages":"3"},"PeriodicalIF":1.7,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10832093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139671557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Metformin suppresses proliferation and glycolysis of gastric cancer by modulating ADAMTS12. 二甲双胍通过调节 ADAMTS12 抑制胃癌的增殖和糖酵解
IF 1.7 4区 医学
Genes and Environment Pub Date : 2024-01-03 DOI: 10.1186/s41021-023-00296-z
Rui Chen, Jianhui Chen, Miaoliang Chen, Shenkang Zhou, Pinlu Jiang
{"title":"Metformin suppresses proliferation and glycolysis of gastric cancer by modulating ADAMTS12.","authors":"Rui Chen, Jianhui Chen, Miaoliang Chen, Shenkang Zhou, Pinlu Jiang","doi":"10.1186/s41021-023-00296-z","DOIUrl":"10.1186/s41021-023-00296-z","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer (GC) is a common malignancy with its morbidity increasing worldwide. Hence, it is imperative to develop effective treatments. Studies have shown that metformin has potential antitumor effects. The objective of this study was to probe the antitumor mechanism of metformin in GC.</p><p><strong>Methods: </strong>The expression of ADAMTS12 in GC tissues and its enrichment pathways were analyzed by bioinformatics methods. ADAMTS12 expression in GC cells was assessed by qRT-PCR. Cell viability and proliferation were analyzed by CCK-8 and colony formation assays, respectively. Extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) of GC cells in different treatment groups were analyzed by Seahorse XP 96, and glycolysis metabolites were detected by corresponding kits. Western blot was employed to analyze the level of glycolysis pathway related protein HK-2, and cell functional assays were conducted to verify the functions of metformin on GC cells. A xenograft model was constructed to validate the inhibitory role of metformin in GC.</p><p><strong>Results: </strong>ADAMTS12 expression was elevated in GC tissues/cells and concentrated in glycolysis pathway. Cell functional assays found that ADAMTS12 promoted the proliferation and glycolysis of GC cells. Rescue experiments showed that metformin could reduce the promoting effect of ADAMTS12 overexpression on the proliferation and glycolysis of GC cells. In vivo studies confirmed that metformin suppressed the proliferation and glycolysis process via ADAMTS12 in GC cells.</p><p><strong>Conclusion: </strong>Metformin can repress the proliferation and glycolysis of GC cells via ADAMTS12. The results suggest the potential of ADAMTS12 being a target for the metformin therapy of GC.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":"46 1","pages":"1"},"PeriodicalIF":1.7,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10763268/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139086496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
NCPAD2 is a favorable predictor of prognostic and immunotherapeutic biomarker for multiple cancer types including lung cancer. NCPAD2 是包括肺癌在内的多种癌症的预后预测和免疫治疗生物标志物。
IF 2.7 4区 医学
Genes and Environment Pub Date : 2024-01-03 DOI: 10.1186/s41021-023-00291-4
Linyuan Feng, Yang Yang, Zhenhua Lin, Minghua Cui, Aihua Jin, Aili Cui
{"title":"NCPAD2 is a favorable predictor of prognostic and immunotherapeutic biomarker for multiple cancer types including lung cancer.","authors":"Linyuan Feng, Yang Yang, Zhenhua Lin, Minghua Cui, Aihua Jin, Aili Cui","doi":"10.1186/s41021-023-00291-4","DOIUrl":"10.1186/s41021-023-00291-4","url":null,"abstract":"<p><strong>Background: </strong>Non-SMC condensin I complex subunit D2 (NCAPD2) belongs to the chromosomal structural maintenance family. While the different contribution of NCAPD2 to chromosome in mitosis have been thoroughly investigated, much less is known about the expression of NCAPD2 in pan-cancer. Thus, we used a bioinformatics dataset to conduct a pan-cancer analysis of NCAPD2 to determine its regulatory role in tumors.</p><p><strong>Methods: </strong>Multiple online databases were analyzed NCAPD2 gene expression, protein level, patient survival and functional enrichment in pan-cancer. Genetic alteration and tumor stemness of NCAPD2 were analyzed using cBioPortal and SangerBox. The GSCA and CellMiner were used to explore the relationship between NCAPD2 and drug sensitivity. The diagnostic value of prognosis was evaluated by ROC curve. Subsequently, the immune infiltration level and immune subtype of NCAPD2 in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) were analyzed using TIMER1 and TISIDB.</p><p><strong>Results: </strong>NCAPD2 gene expression was significantly higher in most cancers and associated with clinical stage and poor prognosis. Genomic heterogeneity of NCAPD2 promoted the occurrence and development of tumors. GO enrichment analysis suggested NCAPD2 might be involved in DNA repair and immune response. NCAPD2 was involved in immune infiltration of LUAD and LUSC. ROC curves showed that NCAPD2 has important prognosis diagnostic value in LUAD and LUSC. Moreover, NCAPD2 was drug sensitive to topotecan, which may be an optimize immunotherapy.</p><p><strong>Conclusions: </strong>It was found that NCAPD2 was overexpressed in pan-cancers, which was associated with poor outcomes. Importantly, NCAPD2 could be a diagnostic marker and an immune related biomarker for LUAD and LUSC.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":"46 1","pages":"2"},"PeriodicalIF":2.7,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10763337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139086497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Selenium biofortification improves bioactive composition and antioxidant status in Plantago ovata Forsk., a medicinal plant. 硒生物强化可改善药用植物车前子的生物活性成分和抗氧化状态。
IF 1.7 4区 医学
Genes and Environment Pub Date : 2023-12-19 DOI: 10.1186/s41021-023-00293-2
Sankalan Dey, Sarmistha Sen Raychaudhuri
{"title":"Selenium biofortification improves bioactive composition and antioxidant status in Plantago ovata Forsk., a medicinal plant.","authors":"Sankalan Dey, Sarmistha Sen Raychaudhuri","doi":"10.1186/s41021-023-00293-2","DOIUrl":"10.1186/s41021-023-00293-2","url":null,"abstract":"<p><strong>Background: </strong>Selenium (Se) is an essential micronutrient for humans, but its deficiency as well as toxicity affects large number of people worldwide. Plantago ovata, a commercially important medicinal plant, is mainly cultivated in western regions of India, where elevated levels of Se have been found in soil. Thus, we evaluated the potential of Se biofortification in P. ovata via phytoremediation and its effect on the bioactive composition.</p><p><strong>Results: </strong>The results showed a significant alteration in various morphological and physiological parameters in a dose-dependent manner. The 10 µM Se dose improved seedling height, biomass and total chlorophyll content. There was a gradual increase in total Se content, with highest accumulation of 457.65 µg/g FW at 500 µM Se treatment. Se positively affected the antioxidative metabolism which was measured from the change in total antioxidant capacity, radical scavenging activity and Metallothionein 2 expression. Increasing levels of Se also affected the PAL activity, total polyphenol and flavonoid content. Caffeic acid, Coumaric acid and Rutin were found to be the most abundant phenolic compounds.</p><p><strong>Conclusions: </strong>Low levels of selenium (below 50 µM) can successfully improve Se accumulation and elicit production of various polyphenols without hampering plant growth. Thus, Se fortification of P. ovata seedlings via phytoremediation appears to be a feasible and efficient way to enhance its nutraceutical value in dietary products.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":"45 1","pages":"38"},"PeriodicalIF":1.7,"publicationDate":"2023-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10729483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138801469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Absolute quantification of DNA damage response proteins. DNA 损伤反应蛋白的绝对定量。
IF 1.7 4区 医学
Genes and Environment Pub Date : 2023-12-18 DOI: 10.1186/s41021-023-00295-0
Shun Matsuda, Tsuyoshi Ikura, Tomonari Matsuda
{"title":"Absolute quantification of DNA damage response proteins.","authors":"Shun Matsuda, Tsuyoshi Ikura, Tomonari Matsuda","doi":"10.1186/s41021-023-00295-0","DOIUrl":"10.1186/s41021-023-00295-0","url":null,"abstract":"<p><strong>Background: </strong>DNA damage response (DDR) and repair are vital for safeguarding genetic information and ensuring the survival and accurate transmission of genetic material. DNA damage, such as DNA double-strand breaks (DSBs), triggers a response where sensor proteins recognize DSBs. Information is transmitted to kinases, initiating a sequence resulting in the activation of the DNA damage response and recruitment of other DDR and repair proteins to the DSB site in a highly orderly sequence. Research has traditionally focused on individual protein functions and their order, with limited quantitative analysis, prompting this study's attempt at absolute quantification of DNA damage response and repair proteins and capturing changes in protein chromatin affinity after DNA damage through biochemical fractionation methods.</p><p><strong>Results: </strong>To assess the intracellular levels of proteins involved in DDR and repair, multiple proteins associated with different functions were quantified in EPC2-hTERT cells. H2AX had the highest intracellular abundance (1.93 × 10<sup>6</sup> molecules/cell). The components of the MRN complex were present at the comparable levels: 6.89 × 10<sup>4</sup> (MRE11), 2.17 × 10<sup>4</sup> (RAD50), and 2.35 × 10<sup>4</sup> (NBS1) molecules/cell. MDC1 was present at 1.27 × 10<sup>4</sup> molecules/cell. The intracellular levels of ATM and ATR kinases were relatively low: 555 and 4860 molecules/cell, respectively. The levels of cellular proteins involved in NHEJ (53BP1: 3.03 × 10<sup>4</sup>; XRCC5: 2.62 × 10<sup>4</sup>; XRCC6: 5.05 × 10<sup>5</sup> molecules/cell) were more than an order of magnitude higher than that involved in HR (RAD51: 2500 molecules/cell). Furthermore, we analyzed the dynamics of MDC1 and γH2AX proteins in response to DNA damage induced by the unstable agent neocarzinostatin (NCS). Using cell biochemical fractionation, cells were collected and analyzed at different time points after NCS exposure. Results showed that γH2AX in chromatin fraction peaked at 1 h post-exposure and gradually decreased, while MDC1 translocated from the isotonic to the hypertonic fraction, peaking at 1 hour as well. The study suggests increased MDC1 affinity for chromatin through binding to γH2AX induced by DNA damage. The γH2AX-bound MDC1 (in the hypertonic fraction) to γH2AX ratio at 1 h post-exposure was 1:56.4, with lower MDC1 levels which may attributed to competition with other proteins.</p><p><strong>Conclusions: </strong>The approach provided quantitative insights into protein dynamics in DNA damage response.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":"45 1","pages":"37"},"PeriodicalIF":1.7,"publicationDate":"2023-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10726557/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138801449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Considerations for the genotoxicity assessment of middle size peptide drugs containing non-canonical amino acid residues. 对含有非典型氨基酸残基的中等大小多肽药物进行遗传毒性评估的考虑因素。
IF 1.7 4区 医学
Genes and Environment Pub Date : 2023-12-13 DOI: 10.1186/s41021-023-00294-1
Masayuki Mishima, Kei-Ichi Sugiyama
{"title":"Considerations for the genotoxicity assessment of middle size peptide drugs containing non-canonical amino acid residues.","authors":"Masayuki Mishima, Kei-Ichi Sugiyama","doi":"10.1186/s41021-023-00294-1","DOIUrl":"https://doi.org/10.1186/s41021-023-00294-1","url":null,"abstract":"<p><strong>Background: </strong>Middle size peptides (MSPs) have emerged as a promising new pharmaceutical modality. We are seeking the best way to assess the non-clinical safety of MSPs.</p><p><strong>Consideration: </strong>The requirements for assessing the genotoxicity of pharmaceuticals differ between small molecule drugs and biotherapeutics. Genotoxicity tests are necessary for small molecule drugs but not for biotherapeutics. MSPs, however, share similarities with both small molecule drugs and biotherapeutics. Here, we describe important points to consider in assessing the genotoxicity of MSP drugs. The current standard of genotoxicity assessment for small molecules may not be entirely appropriate for MSP drugs. MSP drugs need genotoxicity assessment mostly according to the current standard of small molecule drugs.</p><p><strong>Conclusion: </strong>We propose a few modifications to the standard test battery of genotoxicity tests, specifically, the inclusion of an in vitro gene mutation test using mammalian cells, and exclusion of (Q)SAR assessment on MSP-related impurities.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":"45 1","pages":"36"},"PeriodicalIF":1.7,"publicationDate":"2023-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10720048/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138801461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Carcinogenic risk of food additive AF-2 banned in Japan: a case study on reassessment of genotoxicity. 日本禁用食品添加剂 AF-2 的致癌风险:基因毒性再评估案例研究。
IF 1.7 4区 医学
Genes and Environment Pub Date : 2023-12-05 DOI: 10.1186/s41021-023-00292-3
Masami Yamada, Takayoshi Suzuki, Arihiro Kohara, Masamitsu Honma
{"title":"Carcinogenic risk of food additive AF-2 banned in Japan: a case study on reassessment of genotoxicity.","authors":"Masami Yamada, Takayoshi Suzuki, Arihiro Kohara, Masamitsu Honma","doi":"10.1186/s41021-023-00292-3","DOIUrl":"10.1186/s41021-023-00292-3","url":null,"abstract":"<p><strong>Background: </strong>Carcinogenic risk assessment studies have been repeatedly improved and are still being debated to find a goal. Evaluation might be changed if new approaches would be applied to some chemicals which means that new approaches may change the final assessment. In this paper, the risk assessment of a chemical, in particular the proper carcinogenicity, is examined using the long-banned food additive, 2-(2-furyl)-3-(5-nitro-2-furyl)-acrylamide, AF-2, as a case study.</p><p><strong>Results: </strong>First, Ames tests were carried out using strains TA1535, TA100, TA1538, and TA98 and their nitroreductase-deficient strains YG7127, YG7128, YG7129, and YG7130. The results showed that mutagenic activity was reduced by about 50% in the nitroreductase-deficient strains, indicating that part of the mutagenic activity shown in Ames test was due to bacterial metabolism. Second, in vivo genotoxicity tests were conducted, including the one that had not been developed in 1970's. Both a micronucleus test and a gene mutation assay using transgenic mice were negative. Third, assuming it is a genotoxic carcinogen, the virtual safety dose of 550 μg/day was calculated from the TD<sub>50</sub> in rats with a probability of 10<sup>-5</sup>.</p><p><strong>Conclusion: </strong>AF-2 has been shown to be carcinogenic to rodents and has previously been indicated to be genotoxic in vitro. However, the present in vivo genotoxicity study, it was negative in the forestomach, a target organ for cancer, particularly in the gene mutation assay in transgenic mice. Considering the daily intake of AF-2 in the 1970s and its virtually safety dose, the carcinogenic risk of AF-2 could be considered acceptable.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":"45 1","pages":"33"},"PeriodicalIF":1.7,"publicationDate":"2023-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10696715/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138487320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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