Sodium Chloride, Dietary

氯化钠 ,膳食
  • 文章类型: Journal Article
    目的:目前的国际指南推荐家庭血压(BP)测量和低钠和高钾摄入量来管理高血压。我们假设增加家庭血压测量可能会导致更有效地管理钠和钾的摄入量和血压。
    方法:我们检查了家庭血压测量天数与尿钠钾(Na/K)比变化的关系,估计盐和钾的摄入量和血压。我们包括209名健康参与者(平均年龄,55.9岁;56.5%的女性)来自前瞻性队列研究。我们检查了自我测量的家庭BP和现场尿液样本的1年数据。
    结果:在1年内,家庭血压测量的中位数(四分位数范围)天数为324(225-358)。基线平均(SD)Na/K比值,盐和钾的摄入量,早晚SBP,早晚DBP为3.8(2.3),8.5(1.9)克/天,1833.5(416.5)毫克/天,120.4(14.0)mmHg,118.2(14.2)mmHg,79.2(10.1)mmHg,和76.2(10.1)mmHg,分别。在多变量调整线性回归中,β(标准误差)每10天增加的家庭BP测量的数量为-0.031(0.017)的Na/K比,-0.036(0.015)盐摄入量,-1.357(2.797)钾摄入量,-0.178(0.064)上午SBP,-0.079(0.041)用于早晨DBP,晚上SBP为-0.109(0.067),晚上DBP为-0.099(0.045)。此外,男人和女人的关系持续存在,但在服用抗高血压药物的参与者中,盐摄入量的变化更为显著(交互作用P=0.002).
    结论:连续测量家庭血压可能不仅导致血压的自我监测,还有盐摄入量和一些BP指数的下降。
    OBJECTIVE: Current international guidelines recommend home blood pressure (BP) measurement and low sodium and high potassium intakes for the management of hypertension. We hypothesized that increased home BP measurement may result in more effective management of sodium and potassium intakes and BP.
    METHODS: We examined associations of home BP measurement days with changes in the urinary sodium-to-potassium (Na/K) ratio, estimated salt and potassium intakes and BP. We included 209 healthy participants (mean age, 55.9 years; 56.5% women) from a prospective cohort study. We examined 1-year data on self-measured home BP and spot urine samples.
    RESULTS: Median (interquartile range) days of home BP measurement was 324 (225-358) over 1-year. Baseline mean (SD) Na/K ratio, salt and potassium intakes, morning and evening SBP, and morning and evening DBP were 3.8 (2.3), 8.5 (1.9) g/day, 1833.5 (416.5) mg/day, 120.4 (14.0) mmHg, 118.2 (14.2) mmHg, 79.2 (10.1) mmHg, and 76.2 (10.1) mmHg, respectively. In multivariable-adjusted linear regression , β (standard error) per 10 days increase in number of home BP measurement were -0.031 (0.017) for Na/K ratio, -0.036 (0.015) for salt intake, -1.357 (2.797) for potassium intake, -0.178 (0.064) for morning SBP, -0.079 (0.041) for morning DBP, -0.109 (0.067) for evening SBP and -0.099 (0.045) for evening DBP. Additionally, relationships persisted for men and women, but changes in salt intake were more pronounced among participants taking antihypertensive medication (interaction P = 0.002).
    CONCLUSIONS: Continuous measurement of home BP may lead not only to self-monitoring of BP, but also to declines in salt intakes and some BP indices.
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  • 文章类型: Journal Article
    长期过量摄入钠对人类健康产生负面影响。降低食物中钠含量的有效策略包括使用咸味和盐味增强肽,这可以减少钠的摄入量,而不损害的味道或盐的味道。咸味和盐味增强肽天然存在于各种食物中,并且主要表现为由<10个氨基酸组成的短链肽。这些肽主要通过化学或酶促水解方法产生,纯化,并使用超滤+凝胶过滤色谱+液相色谱-串联质谱进行鉴定。本研究回顾了这些纯化和鉴定技术的最新进展,并讨论了评估其咸味感知有效性的方法。此外,该研究探索了四种可能参与咸味感知的生物通道(上皮钠通道,瞬时受体电位香草素1,钙敏感受体(CaSR),和跨膜通道样4(TMC4)),后三者主要在高钠水平下运作。在频道中,咸味增强肽,如γ-谷氨酰肽,可能与钙离子共同激活CaSR通道以参与咸味感知。具有带负电荷的氨基酸侧链或末端基团的咸味增强肽可以替代氯离子并激活TMC4通道,有助于咸味感知。最后,该研究从食品材料约束的角度讨论了使用这些肽的可行性,加工适应性,多功能应用,和跨模态交互,同时强调利用计算技术的重要性。本综述为推进含盐增盐肽作为低钠食品配方中钠代用品的开发和应用提供参考。
    Long-term excessive intake of sodium negatively impacts human health. Effective strategies to reduce sodium content in foods include the use of salty and salt taste-enhancing peptides, which can reduce sodium intake without compromising the flavor or salt taste. Salty and salt taste-enhancing peptides naturally exist in various foods and predominantly manifest as short-chain peptides consisting of < 10 amino acids. These peptides are primarily produced through chemical or enzymatic hydrolysis methods, purified, and identified using ultrafiltration + gel filtration chromatography + liquid chromatography-tandem mass spectrometry. This study reviews the latest developments in these purification and identification technologies, and discusses methods to evaluate their effectiveness in saltiness perception. Additionally, the study explores four biological channels potentially involved in saltiness perception (epithelial sodium channel, transient receptor potential vanilloid 1, calcium-sensing receptor (CaSR), and transmembrane channel-like 4 (TMC4)), with the latter three primarily functioning under high sodium levels. Among the channels, salty taste-enhancing peptides, such as γ-glutamyl peptides, may co-activate the CaSR channel with calcium ions to participate in saltiness perception. Salty taste-enhancing peptides with negatively charged amino acid side chains or terminal groups may replace chloride ions and activate the TMC4 channel, contributing to saltiness perception. Finally, the study discusses the feasibility of using these peptides from the perspectives of food material constraints, processing adaptability, multifunctional application, and cross-modal interaction while emphasizing the importance of utilizing computational technology. This review provides a reference for advancing the development and application of salty and salt-enhancing peptides as sodium substitutes in low-sodium food formulations.
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  • 文章类型: Journal Article
    此内容分析旨在评估有关X的钠减少和血压的错误信息主题,目的是提供解决和揭穿此类错误信息的策略。共有531个帖子被手动编码为与钠有关的错误信息主题,纳入标准的帖子声称钠减少与高血压之间没有关联,或者声称摄入钠对健康有益。计算了每个错误信息主题的数量和帖子频率。岗位特点,包括信息来源,广告和叙述,被编码,并进行相关分析以评估它们与每个错误信息主题的关联.确定了十四个与钠有关的错误信息主题,并在X上不断传播。\'天然盐\',占37.7%(n=200),达到160万粉丝,接着是“减少盐可能对我的健康有害”的主题,占28.6%(n=152),追随者达到150万。天然盐错误信息主题与广告之间存在统计相关性。这项研究中发现的许多最常见的错误信息主题尚未被世界卫生组织和美国心脏协会等组织系统地揭穿。这项研究强调了持续监测和分析社交媒体平台上与钠相关的错误信息及其潜在商业利益的重要性。这种监测有可能确定可能对公众造成伤害的普遍错误信息主题,并告知公共卫生组织,使他们能够通过揭穿主动解决潜在问题。
    This content analysis aimed to assess misinformation themes regarding sodium reduction and blood pressure on X with the goal of providing strategies to address and debunk such misinformation. A total of 531 posts were manually coded into sodium-related misinformation themes, with inclusion criteria for posts asserting no association between sodium reduction and hypertension or claiming consuming sodium is beneficial for health. Numbers and post frequencies per misinformation theme were calculated. Post characteristics, including information sources, advertisements and narratives, were coded, and a correlation analysis was conducted to assess their association with each misinformation theme. Fourteen sodium-related misinformation themes were identified and consistently disseminated on X. The predominant theme, \'Natural Salt\', accounted for 37.7% (n = 200), reaching 1.6 million followers, followed by \'Reducing salt could be bad for my health\' theme, comprising 28.6% (n = 152) and reaching 1.5 million followers. There was a statistical correlation between the natural salt misinformation theme and advertisements. Many of the most frequent misinformation themes identified in this study have not been systematically debunked by organizations such as the World Health Organization and the American Heart Association. This study underscores the importance of continuous monitoring and analysis of sodium-related misinformation on social media platforms and their underlying commercial interests. Such monitoring has the potential to identify prevalent misinformation themes that may pose harm to the public and to inform public health organizations, enabling them to proactively address potential issues through debunking.
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  • 文章类型: Journal Article
    这项研究检查了盐相关知识之间的关联,态度,以及使用24小时(24h)尿液收集方法的行为(KAB)和盐排泄。数据来自尼泊尔非传染性疾病社区管理(COBIN)盐调查,一项基于社区的横断面研究,在博卡拉大都会城的COBIN队列子样本中进行,尼泊尔西部,从2018年7月至12月,在25-70岁的成年人中。共有451名成年人参加了这项研究,并从每个参与者收集一个24小时的尿液样本。参与者的平均[(标准差(SD)]年龄为49.6(9.82)岁,大多数是女性(65%)。平均尿盐排泄为13.28(SD:4.72)g/天,98%的参与者每天摄入≥5g盐。尽管83%的参与者知道高盐摄入量的风险,87%的参与者认为减少摄入量很重要,只有10%的人报告这样做。与盐有关的态度,即,自我感知的盐摄入量与尿盐排泄显着相关,在食物中添加额外的盐,食用加工食品,并采取行动控制盐。认为自己消耗高盐的参与者的尿盐排泄较高[(14.42g/天;95%置信区间(95%CI):13.45,15.39,p=0.03)],更有可能增加额外的[(赔率(OR)=3.59;95%CI:2.03,6.33,p<0.001)],与那些自我感知消耗正常量盐的人相比,他们更经常食用加工食品(OR=1.90;95%CI:1.06,3.40,p<0.05)。相反,与认为摄入正常盐的参与者相比,认为自己摄入低盐的参与者更有可能采取措施控制盐摄入量(OR=4.22;95%CI:1.90,9.37,p<0.001).与盐有关的知识之间存在差距,态度,和实际行为,导致尼泊尔人口的高盐摄入量。尼泊尔迫切需要有针对性的国家减盐计划,其中包括政策和社区层面的干预措施,以便到2025年将平均人口盐摄入量减少30%。需要进一步的验证研究来评估尼泊尔社区干预的有效性。
    This study examined the association between salt-related knowledge, attitudes, and behaviors (KAB) and salt excretion using the 24-hour (24 h) urinary collection method. Data were utilized from the Community-Based Management of Non-Communicable Diseases in Nepal (COBIN) Salt Survey, a community-based cross-sectional study conducted among a sub-sample of COBIN cohort in Pokhara Metropolitan City, Western Nepal, from July to December 2018, among adults aged 25-70 years. A total of 451 adults participated in the study, and a single 24 h urine sample was collected from each participant. The mean [(standard deviation (SD)] age of the participants was 49.6 (9.82) years, and the majority were female (65%). The mean urinary salt excretion was 13.28 (SD: 4.72) g/day, with 98% of participants consuming ≥5 g of salt/day. Although 83% of participants knew the risks of high salt intake and 87% believed it was important to reduce their intake, only 10% reported doing so. Salt-related attitude i.e., self-perceived salt intake was significantly associated with urinary salt excretion, adding extra salt to food, consuming processed foods, and taking actions to salt control. Participants who perceived themselves as consuming high salt had higher urinary salt excretion [(14.42 g/day; 95% confidence interval (95% CI): 13.45, 15.39, p = 0.03)], were more likely to add extra [(Odds ratio (OR) = 3.59; 95% CI: 2.03, 6.33, p < 0.001)], and consume processed foods more often (OR = 1.90; 95% CI: 1.06, 3.40, p < 0.05) compared to those who self-perceived consuming a normal amount of salt. Conversely, participants who perceived themselves as consuming low salt were more likely to take actions to control salt intake (OR = 4.22; 95% CI: 1.90, 9.37, p < 0.001) compared to their counterparts who perceived consuming a normal amount of salt. There existed a gap between salt-related knowledge, attitudes, and actual behaviors, resulting in a high salt intake among the Nepalese population. Nepal urgently requires tailored national salt reduction programs that comprise both policy and community-level interventions to achieve a 30% reduction in mean population salt intake by 2025. Further validation studies are needed to assess the effectiveness of community-based intervention in Nepal.
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  • 文章类型: Journal Article
    与普通盐相比,低钠盐可以不同程度地降低血压。然而,确切的剂量关系尚不清楚.我们旨在研究低钠盐摄入量与收缩压(SBP)和舒张压(DBP)之间的剂量反应关系。以及高血压的风险,并确定低钠盐摄入量的最佳范围。我们调查了350名食用低钠盐的人的基本特征和饮食概况。根据调味品中低钠盐摄入量的第33.3和66.6百分位数将样品分为三组(Q1:<4.72g/d,Q2:≥4.72g/d,和<6.88g/d,和Q3:≥6.88g/d)。约束三次样条结果表明,低钠盐摄入量随SBP和DBP线性下降,虽然低钠摄入量表现出非线性,与高血压风险的L型关系,安全范围为5.81g至7.66g。多元线性回归分析显示,与Q1组相比,Q2组DBP降低了2.843mmHg(95CI:-5.552,-0.133),Q3组SBP下降4.997mmHg(95CI:-9.136,-0.858)。探索性亚组分析表明,低钠盐摄入量对降低男性SBP有显著影响,女性DBP,农村人口中的SBP,和城市人口中的DBP。低钠盐的摄入坚持适度原则,5.81-7.66克可能是一个关键的门槛。
    Compared to common salt, low-sodium salt can reduce blood pressure to varying degrees. However, the exact dosage relationship remains unclear. We aimed to investigate the dose-response relationships between low-sodium salt intake and systolic blood pressure (SBP) and diastolic blood pressure (DBP), as well as the risk of hypertension, and to determine the optimal range for low-sodium salt intake. We investigated the basic characteristics and dietary profile of 350 individuals who consumed low-sodium salt. The samples were divided into three groups according to the 33.3rd and 66.6th percentiles of low-sodium salt intake in condiments (Q1: <4.72 g/d, Q2: ≥4.72 g/d, and <6.88 g/d, and Q3: ≥6.88 g/d). The restricted cubic spline results indicated that low-sodium salt intake decreased linearly with SBP and DBP, while low-sodium intake demonstrated a non-linear, L-shaped relationship with the risk of hypertension, with a safe range of 5.81 g to 7.66 g. The multiple linear regression analysis revealed that compared with group Q1, the DBP in group Q2 decreased by 2.843 mmHg (95%CI: -5.552, -0.133), and the SBP in group Q3 decreased by 4.997 mmHg (95%CI: -9.136, -0.858). Exploratory subgroup analyses indicated that low-sodium salt intake had a significant impact on reducing SBP in males, DBP in females, SBP in rural populations, and DBP in urban populations. The intake of low-sodium salt adheres to the principle of moderation, with 5.81-7.66 g potentially serving as a pivotal threshold.
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  • 文章类型: Journal Article
    美国两个城市要求连锁餐厅标注超过钠每日价值(DV)100%的菜单项,通知消费者,并可能促使餐厅重新配方。为其他地方的政策设计提供信息,这项研究确定了如果对超过20%阈值的菜单项制定警告政策,将被标记的美国前91家连锁餐厅菜单项的百分比,33%,50%,65%,和成人100%的钠DV。我们从2019年MenuStat数据库中获得了美国连锁餐厅的营养信息,并分别计算了所有餐厅以及全服务和有限服务餐厅在食品和饮料类别中需要钠警告标签的物品的百分比。总的来说,19,038个项目包括在分析中。包含>20%的项目的警告标签,>33%,>50%,>65%,>100%的钠DV导致42%的预期覆盖率,30%,20%,13%,和所有餐厅5%的菜单项,分别。在每个阈值,在提供全方位服务的餐厅中,每家餐厅标记的项目的平均百分比高于有限服务的餐厅。这些结果表明,每个项目的钠DV阈值为100%的餐厅警告政策将涵盖少数高钠菜单项,并且应考虑降低阈值以帮助美国消费者减少钠消费。
    Two U.S. cities require chain restaurants to label menu items that exceed 100% of the Daily Value (DV) for sodium, informing consumers and potentially prompting restaurant reformulation. To inform policy design for other localities, this study determined the percentage of the top 91 U.S. chain restaurants\' menu items that would be labeled if a warning policy were established for menu items exceeding the thresholds of 20%, 33%, 50%, 65%, and 100% of the sodium DV for adults. We obtained U.S. chain restaurants\' nutrition information from the 2019 MenuStat database and calculated the percentage of items requiring sodium warning labels across the food and beverage categories at all the restaurants and at the full- and limited-service restaurants separately. In total, 19,038 items were included in the analyses. A warning label covering items with >20%, >33%, >50%, >65%, and >100% of the sodium DV resulted in expected coverage of 42%, 30%, 20%, 13%, and 5% of menu items at all the restaurants, respectively. At each threshold, the average percentage of items labeled per restaurant was higher among the full-service restaurants than the limited-service restaurants. These results suggest that restaurant warning policies with a threshold of 100% of the sodium DV per item would cover a minority of high-sodium menu items and that lower thresholds should be considered to help U.S. consumers reduce their sodium consumption.
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  • 文章类型: Journal Article
    背景:高盐摄入是高血压及其并发症如慢性肾脏病(CKD)和心血管疾病的主要危险因素。本研究旨在确定费洛(塞内加尔中部)农村人口的钠消费水平及其与肾功能的关系。
    方法:我们进行了一项横断面研究,包括400名年龄>18岁的志愿者。临床,家庭访视期间收集生物和饮食数据.在24小时尿输出中测量每日钠摄入量,CKD定义为eGFR<60ml/min。线性回归分析用于评估钠摄入量与协变量之间的关联。
    结果:平均年龄为46.42±15.60,性别比为1.05。高血压的患病率,CKD和超重分别为21.5%、11.7%和20.5%,分别。每日平均盐摄入量为11.7g,四分位数间距为14.8g。只有11.25%的参与者每天摄入少于5g。经过多变量分析,高盐摄入量与年龄>60岁有关,超重和CKD。然而,性别和高血压与盐摄入量无显著相关.工业肉汤(91.5%)和面包(85%)是膳食盐的主要来源。
    结论:这项研究显示,大多数参与者的每日盐摄入量较高,而钾摄入量较低。CKD参与者,超重和年龄>60岁呈现较高的食盐消耗。迫切需要采取减少盐消耗的措施,以减轻塞内加尔农村人口的CKD负担。
    BACKGROUND: High salt intake is a major risk factor for hypertension and its complications such as chronic kidney disease (CKD) and cardiovascular diseases. The present study aimed to determine level of sodium consumption and its relation with kidney function in the rural populations of Ferlo (centre of Senegal).
    METHODS: We performed a cross-sectional study including 400 volunteers aged > 18 years. Clinical, biological and dietary data were collected during household visits. Daily sodium intake was measured in the 24 h-urine outpout and CKD was defined as eGFR < 60 ml/min. Linear regression analysis was used to assess association between sodium intake and covariates.
    RESULTS: Mean age was 46.42 ± 15.60 and sex-ratio was 1.05. Prevalence of hypertension, CKD and overweight were 21.5, 11.7 and 20.5%, respectively. The median daily salt intake was 11.7 g with interquartile range of 14.8 g. Only 11.25% of participants consumed less than 5 g/day. After multivariate analysis, high salt intake was associated with age > 60 years, overweight and CKD. However, gender and hypertension were not significantly associated with salt intake. Industrial broths (91.5%) and bread (85%) represented the main sources of dietary salt.
    CONCLUSIONS: This study revealed high levels of daily salt intake contrasting with low potassium intakes in the majority of participants. Participants with CKD, overweight and age > 60 years presented higher salt consumption. Stategies to reduce salt consumption are urgently needed to reduce burden of CKD in rural Senegalese populations.
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  • 文章类型: Journal Article
    目的:钠摄入过多和钾摄入不足均与血压升高和随后心血管疾病风险增加有关。这是中国和全世界死亡人数最多的国家。低钠盐,主要由氯化钠和氯化钾组成的混合物,已显示出其巨大的潜力,作为一种有希望的人口战略,通过多个大规模减少钠的摄入量,多中心,在包括心血管疾病患者在内的人群中进行随机对照试验,有和没有高血压的人,老年人和年轻人,中国和其他国家的男性和女性。本指南旨在为低钠盐在中国的推广和使用提供专家建议。根据目前关于有效性的现有科学证据,安全,成本效益,以及低钠盐在不同人群和不同应用场景中的可接受性。还向关键利益相关者提出了建议。
    方法:一个工作组,成立了一个专家审查委员会和一个咨询委员会,负责制定指南的范围和要解决的关键问题,为了搜索,合成,评估研究证据,提出和审查建议。使用GRADE网格方法就最终建议达成了共识。
    结果:工作组总结了盐取代的有效性的现有证据,安全,成本效益,可接受性,可用性,适用性,等。该指南提供了六项建议,建议不同人群如何使用低钠盐,关于低钠盐在不同场景中应用的四个建议,以及对关键利益相关者促进盐替代的五点建议。
    结论:关于推广和使用低钠盐的第一个循证指南涵盖了所有相关的关键问题,并将在中国和全世界的高血压和心血管疾病的预防和控制中发挥关键作用。
    OBJECTIVE: Both excessive intake of sodium and inadequate intake of potassium are associated with blood pressure elevation and subsequent increase in the risk of cardiovascular disease, which accounts for the largest number of deaths in China and worldwide. Low sodium salt, a mixture of mainly sodium chloride and potassium chloride, has shown its great potential as a promising population strategy for sodium intake reduction through multiple large-scale, multicenter, randomized controlled trials among populations including patients with cardiovascular disease, individuals with and without hypertension, older and younger adults, and men and women in China and other countries. This Guidelines aims to provide expert recommendations for promotion and use of low sodium salt in China, based on the current available scientific evidence regarding the effectiveness, safety, cost-effectiveness, and acceptability of low sodium salts in various population groups and different application scenarios. The suggestions to key stakeholders are also made.
    METHODS: A working group, an expert review committee and an advisory committee were established to be responsible for formulating the guidelines\' scope and key questions to be addressed, for searching, synthesizing, and evaluating research evidence, proposing and reviewing the recommendations. The consensus on the final recommendations was reached using the GRADE grid method.
    RESULTS: The working group summarized current available evidence of salt substitution regarding its effectiveness, safety, cost-effectiveness, acceptability, availability, suitability, etc. The Guidelines provided six recommendations advising different populations how to use low sodium salt, four recommendations on the application of low sodium salts in different scenarios, and five suggestions for key stakeholders to promote salt substitution.
    CONCLUSIONS: The first evidence-based guidelines on promotion and use of low sodium salts covers all key questions in relevance and would play a critical role in prevention and control of hypertension and cardiovascular disease in China and worldwide.
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  • 文章类型: Journal Article
    几种慢性炎性疾病与高盐(HS)饮食有关。慢性炎症是癌症的既定致病标志。然而,HS饮食在肿瘤发生中的直接作用尚未确定。先前的原位鼠乳腺肿瘤研究表明,短期HS饮食通过激活细胞毒性适应性免疫反应来抑制肿瘤生长。然而,在开发可行的基于HS饮食的慢性小鼠肿瘤模型方面存在实验挑战.为了解决这个问题,我们通过在HS饮食条件下对小鼠肿瘤细胞进行序贯传代,建立了一种新型的慢性HS饮食肿瘤模型.两种原位小鼠三阴性乳腺癌模型,BALB/c小鼠体内注射4T1肿瘤细胞,C57Bl/6小鼠体内注射Py230肿瘤细胞,在我们的研究中使用。对于HS饮食队列,在原位注射肿瘤细胞之前,小鼠保持4%NaCl饮食2周。对于常规盐(RS)饮食队列,小鼠保持1%NaCl饮食。同系癌细胞注射后,肿瘤被允许生长28天,随后收集它们以分离免疫细胞耗尽的癌细胞(第1代,P1)。将来自P1的肿瘤细胞再注射到下一组非荷瘤小鼠中。重复该程序三个循环(P2-P4)。在P1中,与RS饮食队列相比,我们观察到HS饮食下两种小鼠肿瘤模型的肿瘤动力学降低。相比之下,通过P4,HS饮食队列中的肿瘤进展明显高于RS饮食队列.流式细胞术分析表明,HS饮食队列的肿瘤起始干细胞(TISC)从P1到P4增加了8倍。而在RS饮食队列中,TISC频率随着顺序传代而没有显着变化。分子研究显示TGFβR2和CD80在从P4HS饮食队列分离的TISC上的表达增强。体外研究表明,这些TISC的TGFβ刺激增加了CD80分子的细胞表达。Further,在TMSCs中,慢性HS饮食选择性诱导糖酵解代谢表型,而不是线粒体氧化磷酸化表型,这是肿瘤细胞分化和增殖过程中产生代谢物所必需的。P4肿瘤中浸润性CD8和CD4T淋巴细胞显示免疫检查点抑制剂(ICI)CTLA4(CD80的已知结合伴侣)的表达增加,从而引起免疫耗竭和促瘤作用。有趣的是,抗TGFβ单克隆抗体(mAb)在进一步增强抗CTLA4mAb的抗肿瘤作用中起协同作用。总之,我们的研究结果表明,慢性HS饮食增加了肿瘤中TMSCs的频率,导致细胞毒性适应性免疫反应减弱,从而导致肿瘤增殖.此外,抗TGFβ与目前基于ICI的免疫疗法的组合可以发挥更有利的抗癌临床效果.
    Several chronic inflammatory diseases have been linked to high-salt (HS) diets. Chronic inflammation is an established causative hallmark of cancer. However, a direct role of HS diets in tumorigenesis is yet to be defined. Previous orthotopic murine breast tumor studies have shown that short-term HS diets caused inhibition of tumor growth through the activation of cytotoxic adaptive immune responses. However, there have been experimental challenges in developing a viable chronic HS-diet-based murine tumor model. To address this, we have developed a novel chronic HS diet tumor model through the sequential passaging of tumor cells in mice under HS dietary conditions. Two orthotopic murine triple-negative breast cancer models, 4T1 tumor cells injected into BALB/c mice and Py230 tumor cells injected into C57Bl/6 mice, were utilized in our study. For the HS diet cohort, prior to orthotopic injection with tumor cells, the mice were kept on a 4% NaCl diet for 2 weeks. For the regular salt (RS) diet cohort, the mice were kept on a 1% NaCl diet. Following syngeneic cancer cell injection, tumors were allowed to grow for 28 days, following which they were collected to isolate immune cell-depleted cancer cells (passage 1, P1). The tumor cells from P1 were reinjected into the next set of non-tumor-bearing mice. This procedure was repeated for three cycles (P2-P4). In P1, compared to the RS diet cohort, we observed reduced tumor kinetics in both murine tumor models on the HS diet. In contrast, by P4, there was significantly higher tumor progression in the HS diet cohort over the RS diet cohort. Flow cytometry analysis demonstrated an 8-fold increase in tumor-initiating stem cells (TISCs) from P1 to P4 of the HS diet cohort, while there were no significant change in TISC frequency with sequential passaging in the RS diet cohort. Molecular studies showed enhanced expression of TGFβR2 and CD80 on TISCs isolated from the P4 HS diet cohort. In vitro studies demonstrated that TGFβ stimulation of these TISCs increased the cellular expression of CD80 molecules. Further, the chronic HS diet selectively induced the glycolytic metabolic phenotype over the mitochondrial oxidative phosphorylation phenotype in TISCs, which is needed for the production of metabolites during tumor cell differentiation and proliferation. The infiltrating CD8 and CD4 T-lymphocytes in P4 tumors demonstrated increased expression of the immune checkpoint inhibitor (ICI) CTLA4, a known binding partner of CD80, to cause immune exhaustion and pro-tumorigenic effects. Interestingly, anti-TGFβ monoclonal antibodies (mAbs) played a synergistic role in further enhancing the anti-tumor effect of anti-CTLA4 mAb. In summary, our findings demonstrated that chronic HS diet increased the frequency of TISCs in tumors leading to blunting of cytotoxic adaptive immune responses causing tumor proliferation. Furthermore, a combination of anti-TGFβ with current ICI-based immunotherapies could exert more favorable anti-cancer clinical outcomes.
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