Pub Date : 2025-03-01Epub Date: 2024-11-03DOI: 10.1111/nbu.12717
Christian Koeder, Markus Keller
Brazil nuts are well known for their extraordinarily high selenium content. For this reason, they are frequently recommended as a kind of natural selenium 'supplement', particularly for certain population groups such as vegetarians and vegans in regions with low soil selenium levels. Typically, an intake of one or two Brazil nuts per day is recommended. Brazil nuts, however, also stand out from other nuts in terms of their high (albeit highly variable) radium content. The radium isotopes Ra-226 and Ra-228 emit alpha- and beta-radiation, with this type of radiation being particularly harmful when ingested. Consequently, it is important to consider radium levels in Brazil nuts before formulating recommendations for a long-term, daily intake of these nuts. To date, however, no comprehensive overview of radium levels in Brazil nuts has been published. Therefore, a literature review without time or language restrictions was conducted, including unpublished original data from Germany. The literature review (including the German data) indicated mean Ra-226 and Ra-228 levels of 49 (range: 17-205) mBq/g and 67 (range: 12-235) mBq/g, respectively. Assuming a consistent daily intake of one or two Brazil nuts, this would result in an effective dose of ~88-220 μSv/year. This level of exposure appears to be neither clearly harmful nor clearly harmless. As increased radioactivity exposure (at least at higher doses) is associated with increased cancer risk, randomised controlled trials assessing the effect of Brazil nuts on cancer risk biomarkers are needed.
{"title":"Radium levels in Brazil nuts: A review of the literature.","authors":"Christian Koeder, Markus Keller","doi":"10.1111/nbu.12717","DOIUrl":"10.1111/nbu.12717","url":null,"abstract":"<p><p>Brazil nuts are well known for their extraordinarily high selenium content. For this reason, they are frequently recommended as a kind of natural selenium 'supplement', particularly for certain population groups such as vegetarians and vegans in regions with low soil selenium levels. Typically, an intake of one or two Brazil nuts per day is recommended. Brazil nuts, however, also stand out from other nuts in terms of their high (albeit highly variable) radium content. The radium isotopes Ra-226 and Ra-228 emit alpha- and beta-radiation, with this type of radiation being particularly harmful when ingested. Consequently, it is important to consider radium levels in Brazil nuts before formulating recommendations for a long-term, daily intake of these nuts. To date, however, no comprehensive overview of radium levels in Brazil nuts has been published. Therefore, a literature review without time or language restrictions was conducted, including unpublished original data from Germany. The literature review (including the German data) indicated mean Ra-226 and Ra-228 levels of 49 (range: 17-205) mBq/g and 67 (range: 12-235) mBq/g, respectively. Assuming a consistent daily intake of one or two Brazil nuts, this would result in an effective dose of ~88-220 μSv/year. This level of exposure appears to be neither clearly harmful nor clearly harmless. As increased radioactivity exposure (at least at higher doses) is associated with increased cancer risk, randomised controlled trials assessing the effect of Brazil nuts on cancer risk biomarkers are needed.</p>","PeriodicalId":48536,"journal":{"name":"Nutrition Bulletin","volume":" ","pages":"1-11"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11815606/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569961","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}
Pub Date : 2025-03-01Epub Date: 2025-01-20DOI: 10.1111/nbu.12722
Julie Anne Lovegrove
This paper provides a summary of the 2023 British Nutrition Foundation Annual Lecture by Professor Julie Lovegrove. Professor Lovegrove is the head of the Hugh Sinclair Unit of Human Nutrition at the University of Reading. Professor Lovegrove, who was nominated for the BNF Prize for her outstanding contribution to nutritional sciences has published over 300 scientific papers and made a major contribution to establishing the relevance of dietary fat quality in the development and prevention of cardiometabolic disease.
{"title":"Dietary fats and cardiometabolic health-from public health to personalised nutrition: 'One for all' and 'all for one'.","authors":"Julie Anne Lovegrove","doi":"10.1111/nbu.12722","DOIUrl":"10.1111/nbu.12722","url":null,"abstract":"<p><p>This paper provides a summary of the 2023 British Nutrition Foundation Annual Lecture by Professor Julie Lovegrove. Professor Lovegrove is the head of the Hugh Sinclair Unit of Human Nutrition at the University of Reading. Professor Lovegrove, who was nominated for the BNF Prize for her outstanding contribution to nutritional sciences has published over 300 scientific papers and made a major contribution to establishing the relevance of dietary fat quality in the development and prevention of cardiometabolic disease.</p>","PeriodicalId":48536,"journal":{"name":"Nutrition Bulletin","volume":" ","pages":"132-141"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11815623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143014330","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}
Background and aims: Identifying patients with steatotic liver disease who are at a high risk of developing HCC remains challenging. We present a deep learning (DL) model to predict HCC development using hematoxylin and eosin-stained whole-slide images of biopsy-proven steatotic liver disease.
Approach and results: We included 639 patients who did not develop HCC for ≥7 years after biopsy (non-HCC class) and 46 patients who developed HCC <7 years after biopsy (HCC class). Paired cases of the HCC and non-HCC classes matched by biopsy date and institution were used for training, and the remaining nonpaired cases were used for validation. The DL model was trained using deep convolutional neural networks with 28,000 image tiles cropped from whole-slide images of the paired cases, with an accuracy of 81.0% and an AUC of 0.80 for predicting HCC development. Validation using the nonpaired cases also demonstrated a good accuracy of 82.3% and an AUC of 0.84. These results were comparable to the predictive ability of logistic regression model using fibrosis stage. Notably, the DL model also detected the cases of HCC development in patients with mild fibrosis. The saliency maps generated by the DL model highlighted various pathological features associated with HCC development, including nuclear atypia, hepatocytes with a high nuclear-cytoplasmic ratio, immune cell infiltration, fibrosis, and a lack of large fat droplets.
Conclusions: The ability of the DL model to capture subtle pathological features beyond fibrosis suggests its potential for identifying early signs of hepatocarcinogenesis in patients with steatotic liver disease.
{"title":"Deep learning and digital pathology powers prediction of HCC development in steatotic liver disease.","authors":"Takuma Nakatsuka, Ryosuke Tateishi, Masaya Sato, Natsuka Hashizume, Ami Kamada, Hiroki Nakano, Yoshinori Kabeya, Sho Yonezawa, Rie Irie, Hanako Tsujikawa, Yoshio Sumida, Masashi Yoneda, Norio Akuta, Takumi Kawaguchi, Hirokazu Takahashi, Yuichiro Eguchi, Yuya Seko, Yoshito Itoh, Eisuke Murakami, Kazuaki Chayama, Makiko Taniai, Katsutoshi Tokushige, Takeshi Okanoue, Michiie Sakamoto, Mitsuhiro Fujishiro, Kazuhiko Koike","doi":"10.1097/HEP.0000000000000904","DOIUrl":"10.1097/HEP.0000000000000904","url":null,"abstract":"<p><strong>Background and aims: </strong>Identifying patients with steatotic liver disease who are at a high risk of developing HCC remains challenging. We present a deep learning (DL) model to predict HCC development using hematoxylin and eosin-stained whole-slide images of biopsy-proven steatotic liver disease.</p><p><strong>Approach and results: </strong>We included 639 patients who did not develop HCC for ≥7 years after biopsy (non-HCC class) and 46 patients who developed HCC <7 years after biopsy (HCC class). Paired cases of the HCC and non-HCC classes matched by biopsy date and institution were used for training, and the remaining nonpaired cases were used for validation. The DL model was trained using deep convolutional neural networks with 28,000 image tiles cropped from whole-slide images of the paired cases, with an accuracy of 81.0% and an AUC of 0.80 for predicting HCC development. Validation using the nonpaired cases also demonstrated a good accuracy of 82.3% and an AUC of 0.84. These results were comparable to the predictive ability of logistic regression model using fibrosis stage. Notably, the DL model also detected the cases of HCC development in patients with mild fibrosis. The saliency maps generated by the DL model highlighted various pathological features associated with HCC development, including nuclear atypia, hepatocytes with a high nuclear-cytoplasmic ratio, immune cell infiltration, fibrosis, and a lack of large fat droplets.</p><p><strong>Conclusions: </strong>The ability of the DL model to capture subtle pathological features beyond fibrosis suggests its potential for identifying early signs of hepatocarcinogenesis in patients with steatotic liver disease.</p>","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"976-989"},"PeriodicalIF":12.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11825480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141069936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01Epub Date: 2024-06-18DOI: 10.1097/HEP.0000000000000976
Prakash Ramachandran, Frank Tacke
{"title":"Exploring the role of macrophages in the pathogenesis of alcohol-associated liver disease.","authors":"Prakash Ramachandran, Frank Tacke","doi":"10.1097/HEP.0000000000000976","DOIUrl":"10.1097/HEP.0000000000000976","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"762-764"},"PeriodicalIF":12.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141416942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01Epub Date: 2025-01-12DOI: 10.1111/nbu.12729
Danielle I McCarthy
Transformative change is needed across the food system to improve health and environmental outcomes. As food, nutrition, environmental and health data are generated beyond human scale, there is an opportunity for technological tools to support multifactorial, integrated, scalable approaches to address the complexities of dietary behaviour change. Responsible technology could act as a mechanistic conduit between research, policy, industry and society, enabling timely, informed decision making and action by all stakeholders across the food system. Domain expertise in food, nutrition and health should always be integrated into both the development and continuous deployment of AI-powered nutritional intelligence (NI) to ensure it is responsible, accurate, safe, useable and effective. Dietary behaviours are complex and improving diet-related health outcomes requires socio-cultural-demographic considerations within the design and deployment of NI tools. This article describes existing examples of NI within the food system and future opportunities. Human-in-the-loop approaches with food, health and nutrition experts involved at all stages including data acquisition, processing, output validation and ongoing quality assurance are essential to ensure evidence-based practice. The same ethical considerations should apply in this domain as in any other (e.g. privacy, inclusivity, robustness, transparency and accountability) and responsible practice must encompass rigorous standards and alignment with regulatory frameworks. Critical today and in the future is accessibility to appropriate high-quality food compositional data sets, which include up-to-date information on commercially available products that reflect the constantly evolving food landscape to realise the potential of responsible AI to help address the existing food system challenges.
{"title":"Nutritional intelligence in the food system: Combining food, health, data and AI expertise.","authors":"Danielle I McCarthy","doi":"10.1111/nbu.12729","DOIUrl":"10.1111/nbu.12729","url":null,"abstract":"<p><p>Transformative change is needed across the food system to improve health and environmental outcomes. As food, nutrition, environmental and health data are generated beyond human scale, there is an opportunity for technological tools to support multifactorial, integrated, scalable approaches to address the complexities of dietary behaviour change. Responsible technology could act as a mechanistic conduit between research, policy, industry and society, enabling timely, informed decision making and action by all stakeholders across the food system. Domain expertise in food, nutrition and health should always be integrated into both the development and continuous deployment of AI-powered nutritional intelligence (NI) to ensure it is responsible, accurate, safe, useable and effective. Dietary behaviours are complex and improving diet-related health outcomes requires socio-cultural-demographic considerations within the design and deployment of NI tools. This article describes existing examples of NI within the food system and future opportunities. Human-in-the-loop approaches with food, health and nutrition experts involved at all stages including data acquisition, processing, output validation and ongoing quality assurance are essential to ensure evidence-based practice. The same ethical considerations should apply in this domain as in any other (e.g. privacy, inclusivity, robustness, transparency and accountability) and responsible practice must encompass rigorous standards and alignment with regulatory frameworks. Critical today and in the future is accessibility to appropriate high-quality food compositional data sets, which include up-to-date information on commercially available products that reflect the constantly evolving food landscape to realise the potential of responsible AI to help address the existing food system challenges.</p>","PeriodicalId":48536,"journal":{"name":"Nutrition Bulletin","volume":" ","pages":"142-150"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11815607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972818","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}
Pub Date : 2025-03-01Epub Date: 2024-11-25DOI: 10.1111/nbu.12724
Emily Dow, Kinta D Schott, Lindsay Morton, Hannah Lybbert, Kahyun Nam, Colin Shumate, Pamela Kulinna, Floris C Wardenaar
To promote safe supplement use, athletes are advised to choose third-party tested (TPT) supplements to minimise doping risk. This study evaluated changes in knowledge on supplements in US high school athletes from a 2-week online supplement education programme. One group of sophomores (ED, n = 48) completed a Canvas course on safe supplement use, based on the Theory of Planned Behaviour, while the other group of freshmen (NOED, n = 38) did not. Participants completed questionnaires pre- and post-intervention to assess practical knowledge of finding and ordering TPT supplements, familiarity with World Anti-Doping Agency (WADA) banned substances and decision-making in supplement purchasing. Chi-Square and McNemar tests were applied with significance set at p ≤ 0.05. Pre-intervention no differences were found between groups (ages 14-17 years, 39.5% female) for any knowledge questions (p = 0.18). Post-intervention, ED participants were more likely to know where to find (58.3% vs. 39.5%, p = 0.041), and order (62.5% vs. 28.9%, p = 0.001) TPT supplements, and more athletes in ED (72.9%) than NOED (40.0%) reported deciding to purchase supplements themselves (p = 0.015). Parents were less influential in ED (75.0% vs. 92.1%, p = 0.019). Importantly, positive changes over time were larger for ED versus NOED in knowing where to find (28% vs. 13%, p = 0.04) and order (28% vs. 7%, p < 0.001) TPT supplements and WADA familiarity (19% vs. 5%, p = 0.01). Within-group changes showed ED improved on all practical knowledge questions (p = <0.001-0.008), whereas NOED only increased in knowing where to find TPT supplements (p = 0.003). These findings suggest an online educational programme may enhance practical knowledge of safe supplement use among high school athletes.
{"title":"High school athletes' practical knowledge on where to find and order third-party tested nutritional supplements increases after education when compared to a control group.","authors":"Emily Dow, Kinta D Schott, Lindsay Morton, Hannah Lybbert, Kahyun Nam, Colin Shumate, Pamela Kulinna, Floris C Wardenaar","doi":"10.1111/nbu.12724","DOIUrl":"10.1111/nbu.12724","url":null,"abstract":"<p><p>To promote safe supplement use, athletes are advised to choose third-party tested (TPT) supplements to minimise doping risk. This study evaluated changes in knowledge on supplements in US high school athletes from a 2-week online supplement education programme. One group of sophomores (ED, n = 48) completed a Canvas course on safe supplement use, based on the Theory of Planned Behaviour, while the other group of freshmen (NOED, n = 38) did not. Participants completed questionnaires pre- and post-intervention to assess practical knowledge of finding and ordering TPT supplements, familiarity with World Anti-Doping Agency (WADA) banned substances and decision-making in supplement purchasing. Chi-Square and McNemar tests were applied with significance set at p ≤ 0.05. Pre-intervention no differences were found between groups (ages 14-17 years, 39.5% female) for any knowledge questions (p = 0.18). Post-intervention, ED participants were more likely to know where to find (58.3% vs. 39.5%, p = 0.041), and order (62.5% vs. 28.9%, p = 0.001) TPT supplements, and more athletes in ED (72.9%) than NOED (40.0%) reported deciding to purchase supplements themselves (p = 0.015). Parents were less influential in ED (75.0% vs. 92.1%, p = 0.019). Importantly, positive changes over time were larger for ED versus NOED in knowing where to find (28% vs. 13%, p = 0.04) and order (28% vs. 7%, p < 0.001) TPT supplements and WADA familiarity (19% vs. 5%, p = 0.01). Within-group changes showed ED improved on all practical knowledge questions (p = <0.001-0.008), whereas NOED only increased in knowing where to find TPT supplements (p = 0.003). These findings suggest an online educational programme may enhance practical knowledge of safe supplement use among high school athletes.</p>","PeriodicalId":48536,"journal":{"name":"Nutrition Bulletin","volume":" ","pages":"106-119"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142711423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01Epub Date: 2024-10-26DOI: 10.1111/nbu.12716
Eirini Bathrellou, Vasiliki Bountziouka, Despoina Lamprou, Evanthia Fragedaki, Eleftheria Papachristou, Frank Vriesekoop, Meropi D Kontogianni
The high cost of gluten-free products (GFPs) is being discussed as a potential barrier to adherence to a gluten-free diet, rendering monitoring of their pricing an ongoing demand in a market subject to continuous fluctuations. The current study aimed to assess the current pricing status of GFPs in the Greek retail market, with a focus on differences between staple and non-staple foods. The retail price and packaging weight of all available GFPs and their gluten-containing (GCPs) counterparts of a GFP-shopping basket (formulated based on the results of a preceding online survey) were recorded by visiting one store of the five most popular reported supermarket chains. The food categories were grouped into staple (e.g. breads, pasta and flours) and non-staple (e.g. chips, sweets and sauces) foods. Adjusting for supermarket chain and product type, a quantile mixed regression model was applied to assess the extent to which median product price (per 100 g) differed between GFPs and GCPs. The unique products recorded were 1058 (of which 408 GFPs), with a total of 2165 retail price recordings. While the overall median price/100 g of GFPs was not found to be significantly different from that of GCPs, the median price of staple GFPs was estimated to be higher than staple GCPs (+€1.03 [95% CI: €0.93; €1.13] per 100 g), whilst that of non-staple GFPs was slightly lower (-€0.20 [95% CI: -€0.37; -€0.02] per 100 g). In conclusion, the persisting higher cost of staple GFPs suggests the need for ongoing financial support for people with coeliac disease.
{"title":"Higher cost of gluten-free products compared to gluten-containing equivalents is mainly attributed to staple foods.","authors":"Eirini Bathrellou, Vasiliki Bountziouka, Despoina Lamprou, Evanthia Fragedaki, Eleftheria Papachristou, Frank Vriesekoop, Meropi D Kontogianni","doi":"10.1111/nbu.12716","DOIUrl":"10.1111/nbu.12716","url":null,"abstract":"<p><p>The high cost of gluten-free products (GFPs) is being discussed as a potential barrier to adherence to a gluten-free diet, rendering monitoring of their pricing an ongoing demand in a market subject to continuous fluctuations. The current study aimed to assess the current pricing status of GFPs in the Greek retail market, with a focus on differences between staple and non-staple foods. The retail price and packaging weight of all available GFPs and their gluten-containing (GCPs) counterparts of a GFP-shopping basket (formulated based on the results of a preceding online survey) were recorded by visiting one store of the five most popular reported supermarket chains. The food categories were grouped into staple (e.g. breads, pasta and flours) and non-staple (e.g. chips, sweets and sauces) foods. Adjusting for supermarket chain and product type, a quantile mixed regression model was applied to assess the extent to which median product price (per 100 g) differed between GFPs and GCPs. The unique products recorded were 1058 (of which 408 GFPs), with a total of 2165 retail price recordings. While the overall median price/100 g of GFPs was not found to be significantly different from that of GCPs, the median price of staple GFPs was estimated to be higher than staple GCPs (+€1.03 [95% CI: €0.93; €1.13] per 100 g), whilst that of non-staple GFPs was slightly lower (-€0.20 [95% CI: -€0.37; -€0.02] per 100 g). In conclusion, the persisting higher cost of staple GFPs suggests the need for ongoing financial support for people with coeliac disease.</p>","PeriodicalId":48536,"journal":{"name":"Nutrition Bulletin","volume":" ","pages":"44-51"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11815601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142510630","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}
Pub Date : 2025-03-01Epub Date: 2024-01-24DOI: 10.1097/HEP.0000000000000762
Yujia Xia, Yu Wang, Qi Xiong, Jiayi He, Han Wang, Mozaffarul Islam, Xinyu Zhou, Alex Kim, Hongji Zhang, Hai Huang, Allan Tsung
Background and aims: Metabolic dysfunction-associated steatohepatitis (MASH) fibrosis is a reversible stage of liver disease accompanied by inflammatory cell infiltration. Neutrophils extrude a meshwork of chromatin fibers to establish neutrophil extracellular traps (NETs), which play important roles in inflammatory response regulation. Our previous work demonstrated that NETs promote HCC in MASH. However, it is still unknown if NETs play a role in the molecular mechanisms of liver fibrosis.
Approach and results: Following 12 weeks of Western diet/carbon tetrachloride, MASH fibrosis was identified in C57BL/6 mice with increased NET formation. However, NET depletion using DNase I treatment or mice knocked out for peptidyl arginine deaminase type IV significantly attenuated the development of MASH fibrosis. NETs were demonstrated to induce HSCs activation, proliferation, and migration through augmented mitochondrial and aerobic glycolysis to provide additional bioenergetic and biosynthetic supplies. Metabolomic analysis revealed markedly an altered metabolic profile upon NET stimulation of HSCs that were dependent on arachidonic acid metabolism. Mechanistically, NET stimulation of toll-like receptor 3 induced cyclooxygenase-2 activation and prostaglandin E2 production with subsequent HSC activation and liver fibrosis. Inhibiting cyclooxygenase-2 with celecoxib reduced fibrosis in our MASH model.
Conclusions: Our findings implicate NETs playing a critical role in the development of MASH hepatic fibrosis by inducing metabolic reprogramming of HSCs through the toll-like receptor 3/cyclooxygenase-2/cyclooxygenase-2 pathway. Therefore, NET inhibition may represent an attractive treatment target for MASH liver fibrosis.
背景和目的:代谢功能障碍相关性脂肪性肝炎(MASH)-纤维化是肝病的一个可逆阶段,伴有炎症细胞浸润。中性粒细胞挤出染色质纤维网,建立中性粒细胞胞外陷阱(NET),在炎症反应调节中发挥重要作用。我们之前的研究表明,NETs 可促进 MASH 中肝细胞癌的发生。然而,NETs是否在肝纤维化的分子机制中发挥作用仍是未知数:方法和结果:西式饮食(WD)/四氯化碳(CCl4)12 周后,在 C57BL/6 小鼠中发现了 MASH-纤维化,NET 形成增加。然而,使用 DNase I 处理或敲除肽基精氨酸脱氨酶 IV 型(PAD4-/-)的小鼠进行 NET 清除,可显著减轻 MASH 纤维化的发展。实验证明,NETs能通过增强线粒体和有氧糖酵解提供额外的生物能和生物合成供应,诱导肝星状细胞(HSCs)活化、增殖和迁移。代谢组学分析表明,NET 刺激造血干细胞后,造血干细胞的代谢特征发生了明显改变,这种改变依赖于花生四烯酸代谢。从机理上讲,NET刺激toll样受体3(TLR3)会诱导环氧化酶2(COX-2)活化和前列腺素E2(PGE2)的产生,进而导致造血干细胞活化和肝纤维化。在我们的MASH模型中,用塞来昔布抑制COX-2可减少肝纤维化:我们的研究结果表明,NET通过TLR3/COX-2/PGE2途径诱导造血干细胞的代谢重编程,在MASH-肝纤维化的发展过程中发挥了关键作用。因此,抑制NET可能是治疗MASH肝纤维化的一个有吸引力的靶点。
{"title":"Neutrophil extracellular traps promote MASH fibrosis by metabolic reprogramming of HSC.","authors":"Yujia Xia, Yu Wang, Qi Xiong, Jiayi He, Han Wang, Mozaffarul Islam, Xinyu Zhou, Alex Kim, Hongji Zhang, Hai Huang, Allan Tsung","doi":"10.1097/HEP.0000000000000762","DOIUrl":"10.1097/HEP.0000000000000762","url":null,"abstract":"<p><strong>Background and aims: </strong>Metabolic dysfunction-associated steatohepatitis (MASH) fibrosis is a reversible stage of liver disease accompanied by inflammatory cell infiltration. Neutrophils extrude a meshwork of chromatin fibers to establish neutrophil extracellular traps (NETs), which play important roles in inflammatory response regulation. Our previous work demonstrated that NETs promote HCC in MASH. However, it is still unknown if NETs play a role in the molecular mechanisms of liver fibrosis.</p><p><strong>Approach and results: </strong>Following 12 weeks of Western diet/carbon tetrachloride, MASH fibrosis was identified in C57BL/6 mice with increased NET formation. However, NET depletion using DNase I treatment or mice knocked out for peptidyl arginine deaminase type IV significantly attenuated the development of MASH fibrosis. NETs were demonstrated to induce HSCs activation, proliferation, and migration through augmented mitochondrial and aerobic glycolysis to provide additional bioenergetic and biosynthetic supplies. Metabolomic analysis revealed markedly an altered metabolic profile upon NET stimulation of HSCs that were dependent on arachidonic acid metabolism. Mechanistically, NET stimulation of toll-like receptor 3 induced cyclooxygenase-2 activation and prostaglandin E2 production with subsequent HSC activation and liver fibrosis. Inhibiting cyclooxygenase-2 with celecoxib reduced fibrosis in our MASH model.</p><p><strong>Conclusions: </strong>Our findings implicate NETs playing a critical role in the development of MASH hepatic fibrosis by inducing metabolic reprogramming of HSCs through the toll-like receptor 3/cyclooxygenase-2/cyclooxygenase-2 pathway. Therefore, NET inhibition may represent an attractive treatment target for MASH liver fibrosis.</p>","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"947-961"},"PeriodicalIF":12.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139544890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01Epub Date: 2024-05-20DOI: 10.1097/HEP.0000000000000923
Stanislas Pol, Alexander J Thompson, Michelle Collins, Elisa Venier, Laurent Cotte, Montserrat Laguno Centeno, Jorge Mera, Thomas Reiberger, Margaret Burroughs, Dimitri G Semizarov, Alexandru M Iacob, Anne Welhaven, Linda M Fredrick, Joseph S Doyle
Background and aims: No direct-acting antiviral is currently approved for acute HCV infection, delaying treatment. We investigated the effectiveness and safety of 8-week glecaprevir/pibrentasvir (G/P) in patients with acute HCV infection.
Approach and results: This noninterventional, single-arm, retrospective chart review was designed to enroll adults/adolescents with acute HCV infection. Analyses were conducted on a full analysis set (FAS; all enrolled) and modified FAS (FAS excluding nonvirologic failures). The primary end point (modified FAS) was sustained virologic response at posttreatment week 12 (SVR12) with superiority to 92.6% threshold determined by historic chronic HCV G/P SVR12 rates. Secondary end points (FAS) included SVR12, on-treatment virologic failure, posttreatment relapse, and reinfection. Adverse events and safety laboratory values were assessed.Overall, 202 adults were enrolled; in the modified FAS, 150/151 (99.3%; 95% CI: 96.3-99.9) achieved SVR12, demonstrating superiority to efficacy threshold. In the FAS, the SVR12 rate was 74.3% and the on-treatment virologic failure rate was 0%. Relapse and reinfection rates after the final treatment visit (FAS) were 0.5% and 3%, respectively; 39 patients had missing SVR12 data. No on-treatment alanine aminotransferase elevations > 3 × upper limit of normal with total bilirubin > 2 × upper limit of normal were reported. All 53 patients with alanine aminotransferase Grade ≥ 2 at baseline improved to Grade 0/1 on treatment. No adverse eventss of hepatic decompensation/failure or leading to G/P discontinuation occurred. Two patients had serious adverse events unrelated to G/P.
Conclusions: Eight-week G/P therapy was effective and well-tolerated in patients with acute HCV infection. Data support further investigation of G/P in acute HCV to shorten care cascades, reduce transmission, and support HCV elimination.
{"title":"Effectiveness and safety of glecaprevir/pibrentasvir for 8 weeks in the treatment of patients with acute hepatitis C: A single-arm retrospective study.","authors":"Stanislas Pol, Alexander J Thompson, Michelle Collins, Elisa Venier, Laurent Cotte, Montserrat Laguno Centeno, Jorge Mera, Thomas Reiberger, Margaret Burroughs, Dimitri G Semizarov, Alexandru M Iacob, Anne Welhaven, Linda M Fredrick, Joseph S Doyle","doi":"10.1097/HEP.0000000000000923","DOIUrl":"10.1097/HEP.0000000000000923","url":null,"abstract":"<p><strong>Background and aims: </strong>No direct-acting antiviral is currently approved for acute HCV infection, delaying treatment. We investigated the effectiveness and safety of 8-week glecaprevir/pibrentasvir (G/P) in patients with acute HCV infection.</p><p><strong>Approach and results: </strong>This noninterventional, single-arm, retrospective chart review was designed to enroll adults/adolescents with acute HCV infection. Analyses were conducted on a full analysis set (FAS; all enrolled) and modified FAS (FAS excluding nonvirologic failures). The primary end point (modified FAS) was sustained virologic response at posttreatment week 12 (SVR12) with superiority to 92.6% threshold determined by historic chronic HCV G/P SVR12 rates. Secondary end points (FAS) included SVR12, on-treatment virologic failure, posttreatment relapse, and reinfection. Adverse events and safety laboratory values were assessed.Overall, 202 adults were enrolled; in the modified FAS, 150/151 (99.3%; 95% CI: 96.3-99.9) achieved SVR12, demonstrating superiority to efficacy threshold. In the FAS, the SVR12 rate was 74.3% and the on-treatment virologic failure rate was 0%. Relapse and reinfection rates after the final treatment visit (FAS) were 0.5% and 3%, respectively; 39 patients had missing SVR12 data. No on-treatment alanine aminotransferase elevations > 3 × upper limit of normal with total bilirubin > 2 × upper limit of normal were reported. All 53 patients with alanine aminotransferase Grade ≥ 2 at baseline improved to Grade 0/1 on treatment. No adverse eventss of hepatic decompensation/failure or leading to G/P discontinuation occurred. Two patients had serious adverse events unrelated to G/P.</p><p><strong>Conclusions: </strong>Eight-week G/P therapy was effective and well-tolerated in patients with acute HCV infection. Data support further investigation of G/P in acute HCV to shorten care cascades, reduce transmission, and support HCV elimination.</p>","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"1006-1018"},"PeriodicalIF":12.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11825497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141069940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}