斯坦福科学家发现无副作用的“天然Ozempic”

* *Key terms:* BRP (molecule name), biological pathway (生物通路), activates (激活), distinct groups of neurons (特定的神经元群/不同的神经元群), precise way (更精准的方式), appetite and metabolism (食欲和新陈代谢). * *Draft:* 这种被称为BRP的分子通过一种不同但相关的生物通路起作用，并激活大脑中特定的神经元群。这表明它可能提供一种更精准的方式来控制食欲和新陈代谢。 * *Paragraph 2:* "'The receptors targeted by semaglutide are found in the brain but also in the gut, pancreas and other tissues,' said assistant professor of pathology Katrin Svensson, PhD. 'That's why Ozempic has widespread effects including slowing the movement of food through the digestive tract and lowering blood sugar levels. In contrast, BRP appears to act specifically in the hypothalamus, which controls appetite and metabolism.'" * *Key terms:* receptors (受体), semaglutide (司美格鲁肽), gut (肠道), pancreas (胰腺), tissues (组织), assistant professor of pathology (病理学助理教授), Ozempic (奥泽匹克/奥赞匹克 - usually translated as 奥泽匹克 or kept as Ozempic, but standard medical translation often uses the generic name or the brand name. Let's use the brand name Ozempic or translate it. Common translation: 奥泽匹克), widespread effects (广泛效应), digestive tract (消化道), blood sugar levels (血糖水平), hypothalamus (下丘脑). * *Draft:* 病理学助理教授Katrin Svensson博士说：“司美格鲁肽靶向的受体不仅存在于大脑中，还存在于肠道、胰腺和其他组织中。这就是为什么Ozempic（奥泽匹克）具有广泛的作用，包括减缓食物通过消化道的速度和降低血糖水平。相比之下，BRP似乎专门作用于控制食欲和新陈代谢的下丘脑。” * *Paragraph 3:* "Svensson, the senior author of the study published in *Nature*, has also co-founded a company that plans to begin human clinical trials in the near future. The study's lead author is senior research scientist Laetitia Coassolo, PhD." * *Key terms:* senior author (资深作者/通讯作者 - usually "通讯作者" in Chinese academic context, but "资深作者" is literal. "通讯作者" is the standard term for the PI responsible. However, "senior author" specifically refers to the PI, while "corresponding author" is the contact. Often they are the same. Let's use "资深作者" or "通讯作者". "资深作者" fits the literal translation well, but "通讯作者" is more common in Chinese paper descriptions. Let's stick to "资深作者" to be safe or "通讯作者" if context implies leadership. Actually, "senior author" is often translated as 资深作者 or 通讯作者. Let's use 资深作者 to distinguish from corresponding author if needed, but usually, it implies the PI. Let's go with 资深作者 for accuracy to the English term.), *Nature* (《自然》), co-founded (联合创办), human clinical trials (人体临床试验), lead author (第一作者), senior research scientist (高级研究科学家). * *Draft:* 这项发表在《自然》杂志上的研究的资深作者Svensson还联合创办了一家公司，计划在不久的将来开始人体临床试验。该研究的第一作者是高级研究科学家Laetitia Coassolo博士。 * *Paragraph 4:* "**How Artificial Intelligence Led to the Discovery**" * *Draft:* **人工智能如何促成这一发现** * *Paragraph 5:* "The discovery relied heavily on artificial intelligence to sort through a large group of molecules known as prohormones. These molecules are initially inactive but can be cut into smaller fragments called peptides, some of which function as hormones that influence processes like metabolism in the brain and body." * *Key terms:* artificial intelligence (人工智能), sort through (筛选/梳理), prohormones (激素原), inactive (无活性), fragments (片段), peptides (肽), hormones (激素), metabolism (新陈代谢). * *Draft:* 这一发现主要依赖于人工智能来筛选一大类被称为激素原的分子。这些分子最初是无活性的，但可以被切割成称为肽的更小片段，其中一些作为激素发挥作用，影响大脑和身体的新陈代谢等过程。 * *Paragraph 6:* "Because each prohormone can be split in many different ways, identifying useful peptide hormones using traditional lab methods is extremely challenging. Researchers often struggle to distinguish these rare signaling molecules from the many inactive fragments created during normal protein breakdown." * *Key terms:* split (分裂/切割), peptide hormones (肽类激素), traditional lab methods (传统实验室方法), signaling molecules (信号分子), protein breakdown (蛋白质分解). * *Draft:* 由于每种激素原可以以多种不同的方式被切割，使用传统的实验室方法识别有用的肽类激素极具挑战性。研究人员往往难以将这些稀有的信号分子与正常蛋白质分解过程中产生的许多无活性片段区分开来。 * *Paragraph 7:* "To narrow the search, the team focused on an enzyme called prohormone convertase 1/3, which cuts proteins at specific locations and has been linked to obesity. One well-known product of this process is glucagon-like peptide 1, or GLP-1, which helps regulate appetite and blood sugar. Semaglutide works by mimicking GLP-1." * *Key terms:* enzyme (酶), prohormone convertase 1/3 (激素原转化酶 1/3), obesity (肥胖), glucagon-like peptide 1 (胰高血糖素样肽-1), GLP-1, regulate appetite and blood sugar (调节食欲和血糖), mimicking (模拟/模仿). * *Draft:* 为了缩小搜索范围，研究团队专注于一种名为激素原转化酶1/3的酶，这种酶在特定位置切割蛋白质，且与肥胖有关。这一过程的一个著名产物是胰高血糖素样肽-1（GLP-1），它有助于调节食欲和血糖。司美格鲁肽通过模拟GLP-1起作用。 * *Paragraph 8:* "**"Peptide Predictor" Identifies Thousands of Candidates**" * *Draft:* **“肽预测器”识别出数千个候选分子** * *Paragraph 9:* "Instead of relying on traditional protein analysis methods, the researchers developed a computer tool called Peptide Predictor. This algorithm scanned all 20,000 human protein-coding genes to identify where prohormones could be cut into peptides." * *Key terms:* protein analysis methods (蛋白质分析方法), Peptide Predictor (肽预测器), algorithm (算法), protein-coding genes (蛋白编码基因). * *Draft:* 研究人员没有依赖传统的蛋白质分析方法，而是开发了一种名为“肽预测器”的计算机工具。该算法扫描了所有20,000个人类蛋白编码基因，以识别激素原可在何处被切割成肽。 * *Paragraph 10:* "The team then narrowed their focus to proteins that are secreted outside cells, a key feature of hormones, and that contain multiple potential cleavage points. This reduced the list to 373 prohormones suitable for further testing." * *Key terms:* secreted outside cells (分泌到细胞外), key feature (关键特征), cleavage points (切割位点), 373 prohormones. * *Draft:* 随后，团队将重点缩小到那些被分泌到细胞外（这是激素的一个关键特征）且包含多个潜在切割位点的蛋白质。这将名单减少到373种适合进一步测试的激素原。 * *Paragraph 11:* "'The algorithm was absolutely key to our findings,' Svensson said." * *Draft:* Svensson说：“该算法对我们的发现至关重要。” * *Paragraph 12:* "From these proteins, the system predicted 2,683 possible peptides. Researchers selected 100 of them, including GLP-1, and tested how they affected lab-grown brain cells." * *Key terms:* 2,683 possible peptides, lab-grown brain cells (实验室培养的脑细胞). * *Draft:* 从这些蛋白质中，系统预测了2,683种可能的肽。研究人员从中选择了100种（包括GLP-1），并测试了它们对实验室培养的脑细胞的影响。 * *Paragraph 13:* "**A Tiny Peptide With Powerful Effects**" * *Draft:* **一种具有强大功效的微小肽** 3. **Review and Refine:** * *Check consistency:* "Semaglutide" -> 司美格鲁肽. "Ozempic" -> Ozempic (brand name often kept or transl 正如预期，GLP-1显著增加了神经元的活动。然而，一种更小的肽——仅由12个氨基酸组成——引发了更强烈的反应，与对照细胞相比，其活性增强了十倍。 该肽被命名为BRP，源自其母体分子BPM/视黄酸诱导神经特异性蛋白2（BRINP2，即BRINP2相关肽）。 **动物研究显示食欲减退与脂肪减少** 在瘦小鼠和小型猪（后者比小鼠更能反映人类的代谢和饮食模式）中进行测试时，BRP显著减少了食物摄入量。进食前单次注射，在一小时内使摄食量降低了高达50%。 在肥胖小鼠中，连续14天每日注射导致平均体重减轻3克，且主要源于脂肪减少。相比之下，未接受治疗的小鼠在同一时期体重增加了约3克。接受治疗的动物还表现出葡萄糖耐量和胰岛素耐量的改善。 重要的是，这些动物未表现出运动活动、饮水量、类焦虑行为或消化功能的变化。进一步分析证实，BRP通过不同于GLP-1或索马鲁肽的大脑和代谢途径发挥作用。 **一种更具针对性的减肥方法** 研究人员目前正致力于鉴定与BRP相互作用的具体受体，并深入理解其在体内的作用机制。他们也在探索延长其作用时间的方法，以便若其在人体内证实有效，能实现更便捷的用药。 Svensson表示：“几十年来，缺乏治疗人类肥胖的有效药物一直是个问题。我们此前测试过的药物无一能与索马鲁肽降低食欲和体重的效果相提并论。我们非常渴望知晓它在人类身上是否安全有效。” **合作与资助** 该研究汇集了来自加州大学伯克利分校、明尼苏达大学和不列颠哥伦比亚大学的科学家。资金来源包括美国国立卫生研究院（拨款号 R01DK125260、P30DK116074、K99AR081618 和 GM113854），以及斯坦福大学的多个项目、美国心脏协会、嘉士伯基金会和吴蔡人类表现联盟。 Svensson 和 Coassolo 被列为与治疗代谢疾病的 BRP 肽相关专利的发明人，Svensson 也是 Merrifield Therapeutics 公司的联合创始人。