Ferritin, a protein ubiquitously found in living organisms, is well known for its major role in iron homeostasis. However, recent studies in invertebrates have revealed that it possesses diverse physiological functions beyond iron homeostasis. Especially in mollusks, ferritin has been suggested to be involved in functions such as restricting iron availability to pathogens during immune responses, mediating iron transport to specific tissues via hemolymph, and contributing to the formation of mineralized tissues, such as shells and radulae. Furthermore, it has been demonstrated that mollusks possess not only the cytoplasmic ferritin found in vertebrates, but also a secretory ferritin, which contains a signal peptide. This review provides a comprehensive overview of molluscan ferritin, summarizing the broad aspects of its molecular structure and physiological functions.
{"title":"Ferritin in Mollusks: Structural Diversity and Physiological Functions.","authors":"Rui Onishi, Michiko Nemoto","doi":"10.1093/bbb/zbaf176","DOIUrl":"https://doi.org/10.1093/bbb/zbaf176","url":null,"abstract":"<p><p>Ferritin, a protein ubiquitously found in living organisms, is well known for its major role in iron homeostasis. However, recent studies in invertebrates have revealed that it possesses diverse physiological functions beyond iron homeostasis. Especially in mollusks, ferritin has been suggested to be involved in functions such as restricting iron availability to pathogens during immune responses, mediating iron transport to specific tissues via hemolymph, and contributing to the formation of mineralized tissues, such as shells and radulae. Furthermore, it has been demonstrated that mollusks possess not only the cytoplasmic ferritin found in vertebrates, but also a secretory ferritin, which contains a signal peptide. This review provides a comprehensive overview of molluscan ferritin, summarizing the broad aspects of its molecular structure and physiological functions.</p>","PeriodicalId":9175,"journal":{"name":"Bioscience, Biotechnology, and Biochemistry","volume":" ","pages":""},"PeriodicalIF":1.3,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145602427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Carbonic anhydrase accelerates the hydration of carbon dioxide (CO₂) and is an attractive biocatalyst for carbon capture and utilization. Acinetobacter sp. Tol 5 shows high adhesiveness via its cell-surface protein AtaA. We previously demonstrated its application to bacterial immobilization and gas-phase bioproduction. Here, we developed Tol 5 cells expressing carbonic anhydrase and evaluated CO₂ conversion ability as whole-cell biocatalysts. A codon-optimized carbonic anhydrase from Sulfurihydrogenibium yellowstonense (SyCA) was produced in the cytoplasm, but the cells showed little activity as a whole-cell biocatalyst. To enhance activity, we fused six signal peptides (SPs) to SyCA for periplasmic expression. The Omp38-SP fusion of SyCA was properly processed to the mature size, yielding higher whole-cell activity. By contrast, the other constructs were either undetectable or remained unprocessed, resulting in lower activities. These results show that periplasmic expression of SyCA is important for efficient CO₂ hydration in Tol 5 cells as whole-cell biocatalysts.
碳酸酐酶加速二氧化碳的水合作用,是一种有吸引力的碳捕获和利用的生物催化剂。不动杆菌sp. Tol 5通过其细胞表面蛋白AtaA表现出较高的粘附性。我们之前展示了它在细菌固定化和气相生物生产中的应用。在这里,我们开发了表达碳酸酐酶的Tol 5细胞,并评估了作为全细胞生物催化剂的CO₂转化能力。从黄石酸硫氢(SyCA)提取的密码子优化的碳酸酐酶在细胞质中产生,但细胞作为全细胞生物催化剂的活性不高。为了增强活性,我们将六种信号肽(SPs)融合到SyCA中进行质周表达。SyCA的Omp38-SP融合被适当地处理到成熟的大小,产生更高的全细胞活性。相比之下,其他结构要么无法检测到,要么未被处理,导致活性较低。这些结果表明,SyCA作为全细胞生物催化剂在Tol - 5细胞的质周表达对于有效的CO 2水合作用是重要的。
{"title":"Heterologous expression of carbonic anhydrase in Acinetobacter sp. Tol 5 for whole-cell biocatalysis.","authors":"Shogo Yoshimoto, Hiroya Oka, Yuki Ohara, Yan-Yu Chen, Masahito Ishikawa, Katsutoshi Hori","doi":"10.1093/bbb/zbaf137","DOIUrl":"10.1093/bbb/zbaf137","url":null,"abstract":"<p><p>Carbonic anhydrase accelerates the hydration of carbon dioxide (CO₂) and is an attractive biocatalyst for carbon capture and utilization. Acinetobacter sp. Tol 5 shows high adhesiveness via its cell-surface protein AtaA. We previously demonstrated its application to bacterial immobilization and gas-phase bioproduction. Here, we developed Tol 5 cells expressing carbonic anhydrase and evaluated CO₂ conversion ability as whole-cell biocatalysts. A codon-optimized carbonic anhydrase from Sulfurihydrogenibium yellowstonense (SyCA) was produced in the cytoplasm, but the cells showed little activity as a whole-cell biocatalyst. To enhance activity, we fused six signal peptides (SPs) to SyCA for periplasmic expression. The Omp38-SP fusion of SyCA was properly processed to the mature size, yielding higher whole-cell activity. By contrast, the other constructs were either undetectable or remained unprocessed, resulting in lower activities. These results show that periplasmic expression of SyCA is important for efficient CO₂ hydration in Tol 5 cells as whole-cell biocatalysts.</p>","PeriodicalId":9175,"journal":{"name":"Bioscience, Biotechnology, and Biochemistry","volume":" ","pages":"1737-1742"},"PeriodicalIF":1.3,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bifidobacteria are Gram-positive, anaerobic bacteria known for their health-promoting effects. However, a comprehensive analysis of middle- and long-chain fatty acids in bifidobacteria remains elusive. This study aimed to evaluate fatty acid accumulation among 43 strains covering 40 species/subspecies, and to elucidate interspecies and interstrain variations. Analysis of their cell-associated fatty acids revealed significant differences in total fatty acid levels. Bifidobacterium thermacidophilum and related species exhibited notably high accumulation of multiple fatty acids (eg decanoic acid, cis-7-C16:1). Among Bifidobacterium breve strains, M-16V produced significantly more cis-7-C16:1 than the others. Additionally, a homology analysis targeting cyclopropane fatty acid synthase was performed to determine the genetic basis of cis-9,10-methyleneoctadecanoic acid (cyclo-C19:0) production. Only strains possessing the homolog produced cyclo-C19:0. These results highlight substantial variation in fatty acid accumulation among bifidobacteria, which could influence their probiotic functionalities. This study provides a foundation for future research on the health benefits of bifidobacterial fatty acid profiles.
{"title":"Comprehensive analysis of cell-associated fatty acids in Bifidobacterium strains.","authors":"Ryuta Murakami, Jin-Zhong Xiao, Kiyotaka Y Hara, Toshitaka Odamaki, Hiroshi Kikukawa","doi":"10.1093/bbb/zbaf144","DOIUrl":"10.1093/bbb/zbaf144","url":null,"abstract":"<p><p>Bifidobacteria are Gram-positive, anaerobic bacteria known for their health-promoting effects. However, a comprehensive analysis of middle- and long-chain fatty acids in bifidobacteria remains elusive. This study aimed to evaluate fatty acid accumulation among 43 strains covering 40 species/subspecies, and to elucidate interspecies and interstrain variations. Analysis of their cell-associated fatty acids revealed significant differences in total fatty acid levels. Bifidobacterium thermacidophilum and related species exhibited notably high accumulation of multiple fatty acids (eg decanoic acid, cis-7-C16:1). Among Bifidobacterium breve strains, M-16V produced significantly more cis-7-C16:1 than the others. Additionally, a homology analysis targeting cyclopropane fatty acid synthase was performed to determine the genetic basis of cis-9,10-methyleneoctadecanoic acid (cyclo-C19:0) production. Only strains possessing the homolog produced cyclo-C19:0. These results highlight substantial variation in fatty acid accumulation among bifidobacteria, which could influence their probiotic functionalities. This study provides a foundation for future research on the health benefits of bifidobacterial fatty acid profiles.</p>","PeriodicalId":9175,"journal":{"name":"Bioscience, Biotechnology, and Biochemistry","volume":" ","pages":"1700-1705"},"PeriodicalIF":1.3,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145273785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Inulin, a soluble dietary fiber, is widely recognized for its gut health benefits; however, its role in the progression of ulcerative colitis remains unclear. In this study, we investigated the effects of inulin supplementation on colitis induced by administering dextran sodium sulfate (DSS) to BALB/c mice. Mice were fed diets containing 10% inulin or cellulose, followed by administration of 2% DSS in drinking water. Inulin-supplemented mice exhibited a higher disease activity index and more severe epithelial damage compared to cellulose-fed controls. Similar pathological features were observed in mice administered polyethylene glycol to induce osmotic diarrhea, suggesting that increased luminal osmotic pressure may exacerbate colitis. Notably, co-administration of polycarbophil calcium with inulin ameliorated clinical symptoms and attenuated tissue damage. These findings suggest that inulin may aggravate colitis, potentially through increased luminal osmotic pressure. Therefore, managing osmotic diarrhea may represent a therapeutic strategy to mitigate colitis symptoms associated with certain dietary fibers.
{"title":"Inulin exacerbates disease severity in a mouse model of ulcerative colitis by causing osmotic diarrhea.","authors":"Takashi Hosono, Keigo Saito, Yu Arima, Yori Ozaki-Masuzawa, Taiichiro Seki","doi":"10.1093/bbb/zbaf129","DOIUrl":"10.1093/bbb/zbaf129","url":null,"abstract":"<p><p>Inulin, a soluble dietary fiber, is widely recognized for its gut health benefits; however, its role in the progression of ulcerative colitis remains unclear. In this study, we investigated the effects of inulin supplementation on colitis induced by administering dextran sodium sulfate (DSS) to BALB/c mice. Mice were fed diets containing 10% inulin or cellulose, followed by administration of 2% DSS in drinking water. Inulin-supplemented mice exhibited a higher disease activity index and more severe epithelial damage compared to cellulose-fed controls. Similar pathological features were observed in mice administered polyethylene glycol to induce osmotic diarrhea, suggesting that increased luminal osmotic pressure may exacerbate colitis. Notably, co-administration of polycarbophil calcium with inulin ameliorated clinical symptoms and attenuated tissue damage. These findings suggest that inulin may aggravate colitis, potentially through increased luminal osmotic pressure. Therefore, managing osmotic diarrhea may represent a therapeutic strategy to mitigate colitis symptoms associated with certain dietary fibers.</p>","PeriodicalId":9175,"journal":{"name":"Bioscience, Biotechnology, and Biochemistry","volume":" ","pages":"1721-1727"},"PeriodicalIF":1.3,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amniotic fluid (AF) constitutes a dynamic environment containing diverse bioactive molecules derived from both maternal and fetal sources that support fetal development. As the fetus develops in continuous contact with AF, it is plausible that AF influences the formation of the skin epidermis. However, the mechanisms through which AF promotes keratinocyte differentiation remain largely unclear. Here, we showed that goat AF enhanced the expression of key functional proteins involved in epidermal barrier formation, including small proline-rich proteins, loricrin, and transglutaminase. We further obtained the bioactive fractions that promote the expression of these differentiation-related proteins through multistep protein fractionation via column chromatography. Proteomic analysis subsequently revealed 291 candidate proteins, including 85 distinct extracellular proteins, primarily grouped into calcium-binding proteins, proteases and their regulators, extracellular matrix components, and signaling molecules. Collectively, these results suggest that proteins secreted or released into AF contribute to establishing a microenvironment conducive to epidermal differentiation.
{"title":"Proteinaceous components in goat amniotic fluid enhance the expression of keratinocyte differentiation-related proteins.","authors":"Tokuji Tsuji, Mao Ohashi, Rikuto Imai, Yusuke Kawaguchi, Hisateru Yamaguchi, Shuichi Matsuyama, Sho Nakamura, Satoshi Ohkura, Kiyotaka Hitomi","doi":"10.1093/bbb/zbaf138","DOIUrl":"10.1093/bbb/zbaf138","url":null,"abstract":"<p><p>Amniotic fluid (AF) constitutes a dynamic environment containing diverse bioactive molecules derived from both maternal and fetal sources that support fetal development. As the fetus develops in continuous contact with AF, it is plausible that AF influences the formation of the skin epidermis. However, the mechanisms through which AF promotes keratinocyte differentiation remain largely unclear. Here, we showed that goat AF enhanced the expression of key functional proteins involved in epidermal barrier formation, including small proline-rich proteins, loricrin, and transglutaminase. We further obtained the bioactive fractions that promote the expression of these differentiation-related proteins through multistep protein fractionation via column chromatography. Proteomic analysis subsequently revealed 291 candidate proteins, including 85 distinct extracellular proteins, primarily grouped into calcium-binding proteins, proteases and their regulators, extracellular matrix components, and signaling molecules. Collectively, these results suggest that proteins secreted or released into AF contribute to establishing a microenvironment conducive to epidermal differentiation.</p>","PeriodicalId":9175,"journal":{"name":"Bioscience, Biotechnology, and Biochemistry","volume":" ","pages":"1687-1699"},"PeriodicalIF":1.3,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145136532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This study aimed to elucidate the functions of saline-alkaline inducible genes encoding OsCHX11 and OsCHX16, members of the cation/H+ exchanger (CHX) family, under different component of saline-alkaline conditions. Rice biomass under carbonate-based (50 mm Na+ with carbonates) and high-pH (50 mm Na+ without carbonates) conditions was similar, whereas higher Na+/K+ ratio was observed under carbonate-based conditions. Under carbonate-based conditions, only OsCHX16 was significantly expressed, whereas both OsCHX11 and OsCHX16 were highly expressed under high pH conditions. The yeast complementation assay showed that OsCHX11 and OsCHX16 improved the yeast growth under saline, carbonate-based, and high-pH conditions by increasing K+ concentration. Taken together, these results suggest that OsCHX11 and OsCHX16 may contribute to the K+ uptake system under saline-alkaline conditions with or without carbonates at cell level.
本研究旨在阐明阳离子/H+交换剂(CHXs)家族成员OsCHX11和OsCHX16的碱碱诱导基因在不同碱碱条件下的功能。碳酸盐基(50 mM Na+含碳酸盐)和高ph (50 mM Na+不含碳酸盐)条件下的水稻生物量相似,但碳酸盐基条件下Na+/K+比值较高。在碳酸盐基条件下,只有OsCHX16显著表达,而在高pH条件下,OsCHX11和OsCHX16均高表达。酵母互补实验表明,OsCHX11和OsCHX16通过提高K+浓度,在盐水、碳酸盐和高ph条件下促进酵母生长。综上所述,这些结果表明OsCHX11和OsCHX16可能在细胞水平上参与盐碱条件下有或没有碳酸盐的K+吸收系统。
{"title":"Cation/H+ exchangers OsCHX11 and OsCHX16 facilitate potassium transport under saline and saline-alkaline conditions.","authors":"Mami Nampei, Daichi Toyama, Mitsuki Kondo, Nguyen Manh Linh, Akihiro Ueda","doi":"10.1093/bbb/zbaf142","DOIUrl":"10.1093/bbb/zbaf142","url":null,"abstract":"<p><p>This study aimed to elucidate the functions of saline-alkaline inducible genes encoding OsCHX11 and OsCHX16, members of the cation/H+ exchanger (CHX) family, under different component of saline-alkaline conditions. Rice biomass under carbonate-based (50 mm Na+ with carbonates) and high-pH (50 mm Na+ without carbonates) conditions was similar, whereas higher Na+/K+ ratio was observed under carbonate-based conditions. Under carbonate-based conditions, only OsCHX16 was significantly expressed, whereas both OsCHX11 and OsCHX16 were highly expressed under high pH conditions. The yeast complementation assay showed that OsCHX11 and OsCHX16 improved the yeast growth under saline, carbonate-based, and high-pH conditions by increasing K+ concentration. Taken together, these results suggest that OsCHX11 and OsCHX16 may contribute to the K+ uptake system under saline-alkaline conditions with or without carbonates at cell level.</p>","PeriodicalId":9175,"journal":{"name":"Bioscience, Biotechnology, and Biochemistry","volume":" ","pages":"1673-1679"},"PeriodicalIF":1.3,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145231513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Co-administration of histidine and soy isoflavones induced beige adipogenesis in male rats, as demonstrated by the formation of multilocular lipid droplets and increased uncoupling protein 1 gene expression in white adipose tissue. This response was accompanied by fat depot-specific enhancement of mitochondrial activity and suppression of lipogenesis, suggesting the potential for dietary strategies to combat obesity via beige adipocytes activation.
{"title":"Co-administration of histidine and soy isoflavones induces beige adipogenesis in male rats: depot-specific responses in white adipose tissue.","authors":"Riku Asahi, Haruhide Udagawa, Remiko Oshiro, Shigeru Nakajima, Nobuyuki Kanzawa, Yukiko Shimizu, Tadashi Okamura, Takahiko J Fujimi","doi":"10.1093/bbb/zbaf135","DOIUrl":"10.1093/bbb/zbaf135","url":null,"abstract":"<p><p>Co-administration of histidine and soy isoflavones induced beige adipogenesis in male rats, as demonstrated by the formation of multilocular lipid droplets and increased uncoupling protein 1 gene expression in white adipose tissue. This response was accompanied by fat depot-specific enhancement of mitochondrial activity and suppression of lipogenesis, suggesting the potential for dietary strategies to combat obesity via beige adipocytes activation.</p>","PeriodicalId":9175,"journal":{"name":"Bioscience, Biotechnology, and Biochemistry","volume":" ","pages":"1728-1732"},"PeriodicalIF":1.3,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The taste of agricultural products and foods is an important factor in quality evaluation; thus, comparable taste data are useful for their production, marketing, branding, and distribution regardless of when or where the data were obtained. To realize this concept, taste data need to be standardized. In this study, a method for standardizing the sourness and sweetness intensities of apple was established using a taste sensor system and a standard solution prepared from citric acid and sucrose. These taste substances are commonly used for standard solutions of other foods. Polyphenolic compounds that interfere with the sweetness sensor probe were removed from sample solutions using polyvinylpolypyrrolidone. The taste intensities estimated using this method showed good agreement with chemical analysis values highly correlated with human sensory evaluation data.
{"title":"Apple sourness and sweetness intensities standardized using a general-purpose standard solution and a taste sensor system.","authors":"Tomomi Ujihara, Nobuyuki Hayashi, Hidekazu Ikezaki","doi":"10.1093/bbb/zbaf136","DOIUrl":"10.1093/bbb/zbaf136","url":null,"abstract":"<p><p>The taste of agricultural products and foods is an important factor in quality evaluation; thus, comparable taste data are useful for their production, marketing, branding, and distribution regardless of when or where the data were obtained. To realize this concept, taste data need to be standardized. In this study, a method for standardizing the sourness and sweetness intensities of apple was established using a taste sensor system and a standard solution prepared from citric acid and sucrose. These taste substances are commonly used for standard solutions of other foods. Polyphenolic compounds that interfere with the sweetness sensor probe were removed from sample solutions using polyvinylpolypyrrolidone. The taste intensities estimated using this method showed good agreement with chemical analysis values highly correlated with human sensory evaluation data.</p>","PeriodicalId":9175,"journal":{"name":"Bioscience, Biotechnology, and Biochemistry","volume":" ","pages":"1712-1720"},"PeriodicalIF":1.3,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jing Wen, Shuai-Cong Ni, Xiao-Lin-Mo Ma-Hai, Yuan Liu, Xin-Jia Yan
Selaginellin A (Sela A), a derivative from Selaginella tamariscina, exerts antitriple-negative breast cancer effects in MDA-MB-231 cells. Proteomic profiling identified 1136 differentially expressed proteins after Sela A treatment, predominantly downregulated (n = 889). Enrichment analyses revealed that Sela A significantly downregulated pathways critical for DNA repair, replication, and cell cycle progression, while upregulating ribosomal biogenesis and protein processing. Mechanistically, Sela A acts as a PTP1B inhibitor (IC50 = 7.4 μm), binding key residues (PHE-182, GLU-186). This inhibition activates the mechanistic target of rapamycin complex 1 (mTOR). Consequently, mTOR activation stimulates ribosomal synthesis but concurrently triggers a p70S6K-mediated negative feedback loop, degrading IRS1. IRS1 loss suppresses Akt signaling, reducing expression of cell cycle proteins and inducing G1-phase arrest. Thus, Sela A may block MDA-MB-231 cell proliferation via PTP1B inhibition driving mTOR/IRS1/Akt dysregulation.
{"title":"Proteomic profiling reveals selaginellin A-induced blockade of cell cycle in MDA-MB-231 cells.","authors":"Jing Wen, Shuai-Cong Ni, Xiao-Lin-Mo Ma-Hai, Yuan Liu, Xin-Jia Yan","doi":"10.1093/bbb/zbaf139","DOIUrl":"10.1093/bbb/zbaf139","url":null,"abstract":"<p><p>Selaginellin A (Sela A), a derivative from Selaginella tamariscina, exerts antitriple-negative breast cancer effects in MDA-MB-231 cells. Proteomic profiling identified 1136 differentially expressed proteins after Sela A treatment, predominantly downregulated (n = 889). Enrichment analyses revealed that Sela A significantly downregulated pathways critical for DNA repair, replication, and cell cycle progression, while upregulating ribosomal biogenesis and protein processing. Mechanistically, Sela A acts as a PTP1B inhibitor (IC50 = 7.4 μm), binding key residues (PHE-182, GLU-186). This inhibition activates the mechanistic target of rapamycin complex 1 (mTOR). Consequently, mTOR activation stimulates ribosomal synthesis but concurrently triggers a p70S6K-mediated negative feedback loop, degrading IRS1. IRS1 loss suppresses Akt signaling, reducing expression of cell cycle proteins and inducing G1-phase arrest. Thus, Sela A may block MDA-MB-231 cell proliferation via PTP1B inhibition driving mTOR/IRS1/Akt dysregulation.</p>","PeriodicalId":9175,"journal":{"name":"Bioscience, Biotechnology, and Biochemistry","volume":" ","pages":"1663-1672"},"PeriodicalIF":1.3,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Miwako Deguchi, Akemi Hosoda, Tomoe Fukumura, Shigeru Saeki, DongHo Kim
Glucagon dysregulation is a hallmark of type 2 diabetes mellitus (T2DM), yet its early hepatic effects remain unclear. Here, we demonstrate that glucagon-induced gluconeogenesis is markedly enhanced in primary hepatocytes from prediabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a well-established model of human T2DM. Compared to control LETO rats, OLETF hepatocytes showed significantly higher glucagon-stimulated expression of gluconeogenic genes (Pepck, G6pase, and Fbp1) at both mRNA and protein levels, along with elevated glucose production. Notably, mRNA decay analysis revealed prolonged half-lives of gluconeogenic transcripts in OLETF hepatocytes, indicating enhanced mRNA stability as a novel mechanism contributing to increased hepatic glucose output. These findings highlight aberrant glucagon responsiveness and posttranscriptional regulation as potential predisposing factors in genetically susceptible models prior to the onset of overt metabolic abnormality, which may be of interest for preventive or therapeutic strategies for controlling fasting hyperglycemia.
{"title":"Augmented glucagon-induced gluconeogenesis in primary hepatocytes from Otsuka Long-Evans Tokushima Fatty rats.","authors":"Miwako Deguchi, Akemi Hosoda, Tomoe Fukumura, Shigeru Saeki, DongHo Kim","doi":"10.1093/bbb/zbaf133","DOIUrl":"10.1093/bbb/zbaf133","url":null,"abstract":"<p><p>Glucagon dysregulation is a hallmark of type 2 diabetes mellitus (T2DM), yet its early hepatic effects remain unclear. Here, we demonstrate that glucagon-induced gluconeogenesis is markedly enhanced in primary hepatocytes from prediabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a well-established model of human T2DM. Compared to control LETO rats, OLETF hepatocytes showed significantly higher glucagon-stimulated expression of gluconeogenic genes (Pepck, G6pase, and Fbp1) at both mRNA and protein levels, along with elevated glucose production. Notably, mRNA decay analysis revealed prolonged half-lives of gluconeogenic transcripts in OLETF hepatocytes, indicating enhanced mRNA stability as a novel mechanism contributing to increased hepatic glucose output. These findings highlight aberrant glucagon responsiveness and posttranscriptional regulation as potential predisposing factors in genetically susceptible models prior to the onset of overt metabolic abnormality, which may be of interest for preventive or therapeutic strategies for controlling fasting hyperglycemia.</p>","PeriodicalId":9175,"journal":{"name":"Bioscience, Biotechnology, and Biochemistry","volume":" ","pages":"1680-1686"},"PeriodicalIF":1.3,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145028975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}