Comparative Study of Combined Microneedling With Either 1% Lactic Acid Solution or Vitamin D3 or Triamcinolone Acetonide in The Treatment of Alopecia Areata

Alopecia areata (AA) is an immunologically mediated disease characterized by non-scarring hair loss (Madni and Shapiro, 2000). AA is presented by rapid and complete hair loss in one or more round or oval patches, usually on the scalp, beard area, eyebrows, eyelashes, and less commonly, on other hairy areas of the body (Berker et al., 2010 and James et al., 2011) Alopecia areata is a T-cell-mediated autoimmune disease. There is a complicated interplay between loss of immune privilege in the hair follicle, autoimmune-mediated hair follicle damage, and activation of inflammatory pathways that have been argued to explain the development of this disorder, but the exact pathophysiology of AA remains unknown. Hair follicles are infiltrated by autoreactive CD8 and CD4 T lymphocytes, which attack hair follicle-derived autoantigens while sparing the stem compartment (Rajabi et al., 2018).
Alopecia areata can be treated with topical and/or intralesional corticosteroids, which are the treatment of choice. Anthralin, minoxidil, coal tar, and topical immunotherapy are examples of other topical treatments. Systemic immunosuppressants such as cyclosporine, systemic steroids, Janus kinase inhibitors, and methotrexate may be considered in severe resistant cases (lee and lee, 2017).
Intralesional triamcinolone acetonide is preferred in cases of AA , as it is well known as anti-inflammatory and interferes with local immunity of the skin, which helps in the recovery of the disease, but if used in wrong technique or given in a high dose, it might cause all the side effects of corticosteroid, especially skin atrophy (Berker et al., 2010).
Lactic acid is a member of alpha-hydroxy acids. It has been used in the treatment of many skin diseases, like AA and vitiligo. Lactic acid stimulates spontaneous secretion of vascular endothelial growth factor (VEGF) by human reconstructed epidermis. VEGF is an angiogenic cytokine involved in angiogenesis and wound healing and stimulates the growth of hair follicles resulting in recovery of AA. Other studies suggest that lactic acid may act through its irritant effect (Al-Tammimy, 2005).
Vitamin D interacts with the innate and adaptive immune systems in a variety of ways, the majority of which contribute to its downregulation (Nancy and Yehuda, 2009). It has a powerful effect on T and B lymphocytes, influencing their activation responses (Arnson et al., 2007).
All cells of the immune system express 1,25-dihydroxyvitamin D3 receptors (VDRs) and are therefore vulnerable to calcitriol-mediated modulation. Vitamin D3 has the ability to influence the migration and maturation of different dendritic cell subtypes and their production of chemokines and cytokines, giving them an immunoregulatory and tolerogenic role (Illescas-Montes et al., 2019) It has been shown that VDRs are highly expressed in the keratinocytes of human hair follicles and the absence of their expression is associated with reduced hair follicle growth and epidermal differentiation. Reduced VDR expression in the hair follicles of affected areas has also been observed in studies of AA patients' scalp (Çerman et al., 2015).
Microneedling (MN) is a technique that comprises puncturing the skin repeatedly with sterile microneedles (Iriarte et al., 2017). It promotes hair regeneration by triggering stem cells in the hair bulge, which results in the generation of growth factors. It also improves blood circulation to the hair follicles and influences the local immune cells (Chandrashekar et al., 2014). Moreover, combining MN with applied topical drugs facilitates their absorption through the microchannels created within the epidermis (Fertig et al., 2018).

开始日期2023-12-15

申办/合作机构

Zagazig University

JPRN-UMIN000052725 / Suspended

Study on Improvement of Intestinal Environment and Defecation by Intake of lactic acid bacillus A Double-Blind, Placebo-Controlled, Parallel Group Comparison Study - Study on Improvement of Intestinal Environment and Defecation by Intake of lactic acid bacillus A Double-Blind, Placebo-Controlled, Parallel Group Comparison Study

开始日期2023-11-07

申办/合作机构-

JPRN-UMIN000051940 / SuspendedN/A

Double-blind study to confirm the effect of lactic acid bacteria N1487-7 on improving liver function -Placebo-controlled, double-blind, randomized, parallel-group comparative study- - Double-blind study to confirm the effect of lactic acid bacteria N1487-7 on improving liver function -Placebo-controlled, double-blind, randomized, parallel-group comparative study-

开始日期2023-09-12

申办/合作机构-

100 项与乳酸相关的临床结果

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100 项与乳酸相关的转化医学

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100 项与乳酸相关的专利（医药）

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3,498

项与乳酸相关的文献（医药）

2024-12-01·Cellular and molecular life sciences : CMLS

Lactic acid promotes nucleus pulposus cell senescence and corresponding intervertebral disc degeneration via interacting with Akt

Article

作者: Liu, Chao ; Chang, Xian ; Chen, Yuxuan ; Zhai, Yu ; Li, Haiyin ; Qi, Yuhan ; Hu, Zhilei ; Feng, Chencheng ; Li, Yueyang ; Liu, Libangxi ; Zhang, Yuyao ; Lou, Jinhui ; Li, Changqing ; Zhang, Yang ; Zhou, Yue

The accumulation of metabolites in the intervertebral disc is considered an important cause of intervertebral disc degeneration (IVDD). Lactic acid, which is a metabolite that is produced by cellular anaerobic glycolysis, has been proven to be closely associated with IVDD. However, little is known about the role of lactic acid in nucleus pulposus cells (NPCs) senescence and oxidative stress. The aim of this study was to investigate the effect of lactic acid on NPCs senescence and oxidative stress as well as the underlying mechanism. A puncture-induced disc degeneration (PIDD) model was established in rats. Metabolomics analysis revealed that lactic acid levels were significantly increased in degenerated intervertebral discs. Elimination of excessive lactic acid using a lactate oxidase (LOx)-overexpressing lentivirus alleviated the progression of IVDD. In vitro experiments showed that high concentrations of lactic acid could induce senescence and oxidative stress in NPCs. High-throughput RNA sequencing results and bioinformatic analysis demonstrated that the induction of NPCs senescence and oxidative stress by lactic acid may be related to the PI3K/Akt signaling pathway. Further study verified that high concentrations of lactic acid could induce NPCs senescence and oxidative stress by interacting with Akt and regulating its downstream Akt/p21/p27/cyclin D1 and Akt/Nrf2/HO-1 pathways. Utilizing molecular docking, site-directed mutation and microscale thermophoresis assays, we found that lactic acid could regulate Akt kinase activity by binding to the Lys39 and Leu52 residues in the PH domain of Akt. These results highlight the involvement of lactic acid in NPCs senescence and oxidative stress, and lactic acid may become a novel potential therapeutic target for the treatment of IVDD.

2024-04-01·The American journal of emergency medicine

Lactate combined with SOFA score for improving the predictive efficacy of SOFA score in patients with severe heatstroke

Article

作者: Tang, Yun ; Wang, Jinhai ; Zhang, He ; Liu, Fujing ; Jin, Fang ; Gu, Tijun ; Zhang, Lingling

BACKGROUND:

The relationship between lactate levels and multiple organ dysfunction in patients with severe heatstroke remains unclear. In this study, we aimed to elucidate the clinical significance of lactate in severe heatstroke prognosis and assess whether incorporating lactate in the SOFA score improves its predictive efficacy.

METHODS:

This study was a multicenter retrospective cohort investigation included 275 patients. Logistic regression analysis was performed to examine the relationship between lactate levels and patient outcomes and complications, including acute kidney injury (AKI), disseminated intravascular coagulation (DIC), and myocardial injury. Further, receiver operating characteristic (ROC) curves and clinical decision curve analysis (DCA) were used to evaluate the predictive power of lactate and SOFA scores in severe heatstroke-associated death. Lastly, the Kaplan-Meier survival curve was employed to differentiate the survival rates among the various patient groups.

RESULTS:

After adjusting for confounding factors, lactate was demonstrated as an independent risk factor for death (OR = 1.353, 95% CI [1.170, 1.569]), AKI (OR = 1.158, 95% CI [1.007, 1.332]), DIC (OR = 1.426, 95% CI [1.225, 1.659]), and myocardial injury (OR = 2.039, 95% CI [1.553, 2.679]). The area under the curve (AUC) of lactate for predicting death from severe heatstroke was 0.7540, with a cutoff of 3.35. The Kaplan-Meier survival curve analysis showed that patients with elevated lactate levels had higher mortality rates. Additionally, the ROC curves demonstrated that combining lactate with the SOFA score provided better predictive efficacy than the SOFA score alone in patients with severe heatstroke (AUC: 0.9025 vs. 0.8773, DeLong test, P < 0.001). Finally, the DCA curve revealed a higher net clinical benefit rate for lactate combined with the SOFA score.

CONCLUSIONS:

Lactate is an independent risk factor for severe heatstroke-related death as well as a risk factor for AKI, DIC, and myocardial injury associated with severe heatstroke. Thus, combining lactate with the SOFA score can significantly improve its predictive efficacy in patients with severe heatstroke.

2024-03-01·The Science of the total environment

Feed materials – Levels and characteristic profiles of dioxins and PCBs

Article

作者: Mikolajczyk, S ; Pajurek, M ; Warenik-Bany, M

Dioxins (PCDD/PCDF) are toxic compounds that are ubiquitous in the environment; although present in low concentrations, they are persistent and highly toxic and they bioaccumulate in food chains. Therefore, it is very important that feed is free of these types of contaminants, because otherwise they can become a source that can negatively affect animal health and the safety of food of animal origin. The aim of the study was to comprehensively assess the concentrations of dioxins and polychlorinated biphenyls (PCBs) in a variety of feed materials available on the Polish market. In addition, characteristic profiles of congeners for given categories of feeds were investigated and defined. Approximately 95 % of the 523 samples of various feed materials tested over seven years (2013-2018 and 2022) met the requirements of European Union feed law (Commission Regulation 277/2012/EU). The highest average PCDD/PCDF/dl-PCB concentrations were found in fish oils and meal and were respectively 1.17 ± 0.78 and 5.51 ± 4.51 ng WHO-TEQ/kg of feed at 12 % moisture. Median and background level concentrations of PCDD/PCDFs, dl-PCBs, PCDD/PCDF/dl-PCBs, and ndl-PCBs were significantly lower than their average concentrations for each individual feed material category. The WHO-TEQ profiles enabled the identification of three different characteristic profiles in feed materials.

项与乳酸相关的新闻（医药）

2024-05-15

·生物谷

晚讯｜中国生物制药“安罗替尼”三阴性乳腺癌研究成果登柳叶刀子刊、业绩狂飙400亿后，华东医药计划分红10亿

1. 中国生物制药“安罗替尼”三阴性乳腺癌研究成果登柳叶刀子刊中国生物制药「安罗替尼」联合紫杉烷类及洛铂新辅助治疗三阴性乳腺癌（TNBC）研究成果发表在《柳叶刀》子刊，显示该方案抗肿瘤效果达到预期，且总缓解率较高，为不适合传统化疗方案的TNBC患者提供了新的治疗选择。该研究由齐晓伟教授团队主导，基于TNBC的生物学特性进行探索，有望改善患者的预后。2. 业绩狂飙400亿后，华东医药计划分红10亿华东医药宣布派发10.18亿元现金红利，为近年来医药行业罕见的分红规模。该公司2023年营收和净利润均实现增长，得益于其医药工业板块的强劲表现，特别在肿瘤领域的创新药产品获批上市。尽管行业面临挑战，华东医药的分红举措仍显示了其稳健的财务状况和市场信心。3. 国产液相色谱龙头平台依利特科技获亿元A+轮融资，助推产品线结构升级及海外市场拓展2024年5月15日，苏州依利特科技有限公司近日完成亿元A+轮融资。本轮融资由君信资本、国泰君安创新投资联合领投，熠美投资跟投，启峰资本持续担任独家财务顾问。这是依利特科技继2024年1月完成超亿元的首轮融资后，又完成的新一轮融资。依利特科技是国内领先的具有自主研发能力并实现产品批量化生产的液相色谱企业，国产HPLC市场占有率领先，公司通过逾百项核心专利的布局，实现了液相色谱核心部件的自主知识产权化。4. 灵眸医疗完成数千万元Pre-A融资，加速内镜全场景时代到来近期，软性内窥镜科室级解决方案提供商杭州灵眸医疗科技有限公司宣布完成数千万人民币Pre-A融资。本轮由海邦沣华领投，跃为资本担任长期独家财务顾问。本轮融资将用于推进公司获批产品的商业化，以及进一步强化补充公司的内镜产品组合，提升综合竞争优势。对于获得本轮融资，灵眸医疗管理层表示：灵眸一直以来致力于推动中国软式内窥镜的发展和渗透，从创立之初，公司就从产品技术底层逻辑出发建立研发体系，不断打磨产品细节，来为临床与患者提供更高质量的内窥镜产品，促使更多风险人群能够从内窥镜的诊疗中获益。在此基础之上，灵眸会继续发力新技术、新产品的迭代，进而满足广泛内镜术者更多样、创新的临床需求。同时，在此产品获证之关键期，公司也将不断提升营销团队实力，着力于快速、高效的产品的商业化与推广，在中国内窥镜市场中突出重围。5. 华东医药“童颜针”将启动注册临床，有望成为国内第四个获批产品华东医药的“童颜针”产品Lanluma即将启动注册临床，有望成为国内第四个获批的聚左旋乳酸医美填充剂。该产品具有刺激胶原蛋白再生的能力，可提供长效填充效果。目前国内已有三款类似产品获批，市场前景良好，但“童颜针”售价高且毛利可观。6. 智愈医疗完成超6000万元Pre-A++轮融资，利用水刀机器人打造标准化、自动化的BPH治疗范式2024年5月14日，北京智愈医疗科技有限公司于近期正式完成超6000万元Pre-A++轮融资。本轮融资由辰德资本领投，联想之星跟投，老股东顺为资本、礼来亚洲基金（LAV）、众海投资持续加注。凡卓资本担任本轮融资独家财务顾问。本轮超募融资所募集资金将用于核心产品metaFlow®️高能水射流自主执行手术机器人（水刀手术机器人）的临床试验，以及新产品管线研发布局。本文仅用于学术分享，转载请注明出处。若有侵权，请联系微信：bioonSir 删除或修改！

2024-05-15

·PRNewswire

Evofem Biosciences Announces Financial Results for the First Quarter of 2024

SAN DIEGO, May 15, 2024 /PRNewswire/ -- The company behind the hormone-free contraceptive Phexxi® (lactic acid, citric acid and potassium bitartrate), Evofem Biosciences, Inc. ("Evofem" or "the Company") (OTCQB: EVFM) today announced financial results for the first quarter of 2024. Highlights of and since the quarter include: Received $1 million from Aditxt, Inc. (Nasdaq: ADTX) in May 2024 in consideration for reinstating and amending the Merger Agreement, as amended, between the companies. Aditxt agreed to invest an additional $2.5 million in Evofem by July 1, 2024. The companies are working to close the contemplated transaction in the second half of 2024. Strengthened Phexxi intellectual property with the allowance of a new Composition of Matter Patent by the USPTO. Once issued, this will be the fifth U.S. patent covering Evofem's hormone-free contraceptive. Launched a partnership with Modern Remedies, one of the top pharmacies dispensing Phexxi in the Northeast, effective May 2024. Successfully renegotiated the rebate for Phexxi with Medi-Cal, the California state Medicaid program serving more than 15.4 million beneficiaries. Effective July 1, 2024, Evofem will pay a 7.4% lower rebate to Medi-Cal on Phexxi prescriptions dispensed to its beneficiaries. Net sales were $3.6 million for the first quarter of 2024, reflecting anticipated cyclical softness following the wholesale acquisition cost (WAC) increase on January 1, 2024, and the impact of the cyberattack on Change Healthcare on February 19, 2024. Total operating expenses decreased 31% vs. the first quarter of 2023 to $6.4 million. Narrowed loss from operations to $2.8 million, a 21% improvement compared to the first quarter of 2023. "We expect 2024 will be our fourth consecutive year of net sales growth, driven in part by continued execution of our market access strategy with payer wins and successful rebate reductions," said Saundra Pelletier, Evofem's CEO. "We also expect lift from increasing use of Phexxi for supplemental contraception among women of reproductive age who take oral birth control pills in conjunction with GLP-1 agonists like Mounjaro and Zepbound. These drugs may make oral contraceptives less effective at certain points in the dosing schedule – specifically for four weeks after initiation and for another four weeks after each dose escalation. Adding a hormone-free, woman-controlled contraceptive like Phexxi is a logical choice for these patients for additional protection against unintended pregnancy during these times." Financial Results For the three months ended March 31, 2024, net sales were $3.6 million compared to $5.8 million in the prior year period. The 38% decrease reflects cyclical softness related to the timing of orders relative to WAC increases and the unfavorable impact of the cyberattack on Change Healthcare. The typical cycle is that our customers A) place larger orders ahead of a price increase, B) sell from this inventory for several months after the price increase, and C) resume ordering the following quarter. Phexxi WAC increased on January 1, 2024, resulting in softer first quarter 2024 net sales (stage B). By contrast, following the October 2022 WAC increase and the near-absence of sales in the fourth quarter of 2022, net sales in the first quarter of 2023 were strong (stage C). Following the cyberattack on Change Healthcare on February 19, 2024, retail pharmacies across the country experienced delays processing prescriptions and were unable to send orders through insurance plans, and there were delays in the processing of insurance claims, which lowered dispensed units of many prescription products, including Phexxi. Additionally, Change Healthcare was the sole adjudicator (processor) used by Evofem's co-pay card vendor and Evofem received no claims for several weeks following the cyberattack. In mid-March, our co-pay card vendor established an alternative adjudicator. Initially the cost to Evofem was significantly higher, which negatively impacted our first quarter results. Costs have dropped back down in the second quarter of 2024 to approximately 8% above pre-cyberattack levels. Total operating expenses decreased 31% to $6.4 million, compared to $9.4 million in the prior year period. The improvement reflects a 39% decrease in selling and marketing costs and 22% decrease in general and administrative costs. As a result, loss from operations improved to $2.8 million, compared with a loss from operations of $3.6 million for the three months ended March 31, 2023. Liquidity At March 31, 2024, we had $0.7 million of restricted cash, as compared to $0.6 million of restricted cash at December 31, 2023. Subsequent to the quarter close, in April 2024 Evofem made the required quarterly payment of $0.1 million to a U.S.-based, healthcare-focused institutional investor as required by the Fourth Amendment to the Securities Purchase and Security Agreement dated April 2020, as amended, under which this investor purchased $25 million of convertible senior secured promissory notes from Evofem in 2020. In May 2024, Evofem received $1 million from Aditxt in consideration of reinstating and amending the Agreement and Plan of Merger, as amended on January 10, 2024, January 30, 2024, February 29, 2024, and May 2, 2024, by and between the companies. Under the Fourth Amendment to the Agreement and Plan of Merger, Aditxt agreed to invest an additional $2.5 million in Evofem by July 1, 2024. The companies are working to close the contemplated transaction in the second half of 2024. About Evofem Biosciences Evofem Biosciences, Inc., is developing and commercializing innovative products to address unmet needs in women's sexual and reproductive health. The Company's first FDA-approved product, Phexxi® (lactic acid, citric acid and potassium bitartrate), is a hormone-free, on-demand prescription contraceptive vaginal gel. It comes in a box of 12 pre-filled applicators and is applied 0-60 minutes before each act of sex. Learn more at phexxi.com and evofem.com. Phexxi® is a registered trademark of Evofem Biosciences, Inc. Forward-Looking Statements This press release includes "forward-looking statements" within the meaning of the safe harbor for forward-looking statements provided by Section 21E of the Securities Exchange Act of 1934, as amended, and the Private Securities Litigation Reform Act of 1995 including, without limitation, statements related to the Company's anticipated financial performance, the anticipated benefits of the contemplated Aditxt transaction, and timing thereof. You are cautioned not to place undue reliance on these forward-looking statements, which are current only as of the date of this press release. Each of these forward-looking statements involves risks and uncertainties. Important factors that could cause actual results to differ materially from those discussed or implied in the forward-looking statements are disclosed in the Company's SEC filings, including its Annual Report on Form 10-K for the year ended December 31, 2023, filed with the SEC on March 27, 2024, its Quarterly Report on Form 10-Q for quarter ended March 31, 2024, filed with the SEC on May 15, 2024, and any subsequent filings. All forward-looking statements are expressly qualified in their entirety by such factors. The Company does not undertake any duty to update any forward-looking statement except as required by law. Contact Amy Raskopf Evofem Biosciences, Inc. [email protected] (917) 673-5775 -- Financial Tables Follow -- SOURCE Evofem Biosciences, Inc.

财报上市批准并购

2024-05-04

·生物谷

你知道吗？看似平平无奇的乳酸，却是癌症的帮凶！乳酸不仅是肿瘤细胞代谢过程中的产物，还通过多种机制促进肿瘤的生长和扩散。乳酸能够作为能量底物支持肿瘤细胞的生存，激活关键信号通路，促进肿瘤细胞的侵袭、转移、血管生成以及免疫逃逸。最近苏州大学的周芳芳教授团队揭示了乳酸促进肿瘤细胞生长的机理。他们发现丙氨酰tRNA合成酶（AARS1）作为乳酸的传感元件，在肿瘤细胞中促进全局性的赖氨酸乳酰化过程。具体而言，有个叫丙氨酰tRNA合成酶（AARS1）的小家伙，竟然在肿瘤细胞里兼职当起了乳酸的“雷达”——AARS1通过与乳酸结合，催化生成乳酸-AMP复合物，促进p53蛋白的乳酸化，导致其活性异常，阻碍了细胞周期的调节并刺激肿瘤生长。这一成果以“Alanyl-tRNA synthetase, AARS1, is a lactate sensor and lactyltransferase that lactylates p53 and contributes to tumorigenesis”为题被发表在《细胞》上。癌症的一大特征是代谢失衡，可以简单理解为癌细胞的“节能模式”，即多数癌细胞在氧气充足的情况下，仍偏好进行有氧糖酵解（Warburg效应，表现为“吃糖”不完全），故意产生大量乳酸，这不仅改变了周围的居住环境，还为自己准备了一堆“能量零食”——乳酸。乳酸不仅影响免疫细胞分化、肿瘤免疫监测、纤维化及缺血性伤害等生物学过程，还能通过蛋白乳酸化这一表观遗传修饰方式调控基因表达，尽管如此，乳酸在细胞内被识别并转化为蛋白乳酸化的具体机制仍有待阐明。在该研究中，研究团队用蛋白质组学方法发现了众多AARS1作用靶点，特别是p53的DNA结合域中两个关键位点——赖氨酸120和赖氨酸139，它们可被乳酸化。通过使用模拟内在乳酸化状态的p53变体进行实验，科研人员观察到，p53上的AARS1介导乳酸化会抑制其液-液相分离能力、DNA结合功能及转录激活作用。在野生型p53存在的癌症病患中，AARS1的高表达与p53的乳酸化水平与不良预后相关联。动物模型实验进一步揭示，补充β-丙氨酸能有效阻止乳酸与AARS1的相互作用，减少p53的乳酸化程度，从而减轻肿瘤的发展，这一发现彰显了AARS1通过连接肿瘤细胞的新陈代谢与蛋白质组变化，在肿瘤发生机制中的关键角色。作为多功能的肿瘤抑制因子，p53可以激活多条防御途径，维护细胞免于癌变，这些途径涉及DNA修复、细胞周期控制及应对压力的生存机制。不幸的是，p53在肿瘤进展中频繁遭受抑制，半数以上的癌症携带有损其抑癌功能的突变。此外，p53的活性还受磷酸化、乙酰化、泛素化等多种翻译后修饰的精细调控。因此深化对p53调控机制的理解，有望为癌症治疗开辟新径，恢复或增强p53的抗癌功能。AARS1作为乳酸传感器和乳酰基转移酶，图片来源于[1]该研究借助CRISPR筛选技术，揭示了AARS1作为细胞内乳酸感知器的功能，它直接结合乳酸并催化蛋白质的全局赖氨酸乳酸化，p53蛋白也在其作用范围内。AARS1利用ATP辅助生成乳酸-AMP中间体，将乳酸共价连接至赖氨酸残基，介导了蛋白组水平的赖氨酸乳酸化。此外，大肠杆菌的AlaRS（EcAlaRS）也被证实能跨物种催化真核蛋白及p53的乳酸化，可见AARS1的乳酸转移酶活性具有深远的进化历史和高度保守性。AARS1能够诱导p53的DNA结合域发生特定位点乳酸化，阻碍其与p53响应元件DNA的结合，进而干扰p53的液相分离与转录活性。研究还提出利用β-丙氨酸竞争性结合AARS1以抑制p53乳酸化，为增强化疗效果提供了新策略。这些研究成果不仅丰富了蛋白质乳酸化的基本理论，还直接阐明了代谢产物乳酸与肿瘤发生发展的紧密联系。科研人员此前就发现乳酸对肿瘤生长有促进作用，比如在2023年底，同济大学医学院/附属东方医院袁健教授的团队同样是在《细胞》上发表了题为“Metabolic Regulation of Homologous Recombination Repair by MRE11 Lactylation”的论文，他们发现乳酸能够帮助肿瘤细胞躲避化疗药物的杀伤，从而导致化疗耐药性。具体来说，乳酸能通过使DNA修复关键蛋白MRE11乳酸化，进而促进同源重组修复（HR），导致化疗耐药，犹如给肿瘤细胞穿上一件”‘金钟罩铁布衫“。乳酸脱氢酶A低表达与HR下调相关，说明乳酸参与了HR调控。提高细胞乳酸化水平可促进HR修复，使肿瘤细胞耐药。MRE11在乙酰转移酶CBP催化下发生乳酸化，K673是其主要修饰位点。高水平的MRE11 K673乳酸化促进DNA结合与修复，导致耐药。抑制这种修饰能显著提升化疗效果，表明这是一种潜在的化疗增效策略。综上所述，乳酸在肿瘤的多过程中扮演着多重角色，既是能量供应商，又是信号传导的使者，还是调控基因的高手。科学家们正努力揭开乳酸的神秘面纱，希望找到更多像β-丙氨酸这样的“奇兵”，通过抑制乳酸的作用，或是干扰它的代谢路径，给抗肿瘤治疗带来新的希望。未来，我们或许能在与癌症的战斗中，依靠这些科学新发现，给肿瘤细胞来个“酸爽”的反击！参考文献：[1]. Zong Z, Xie F, Wang S, et al. Alanyl-tRNA synthetase, AARS1, is a lactate sensor and lactyltransferase that lactylates p53 and contributes to tumorigenesis. Cell. Published online April 17, 2024. doi:10.1016/j.cell.2024.04.002[2]. Chen Y, Wu J, Zhai L, et al. Metabolic regulation of homologous recombination repair by MRE11 lactylation. Cell. 2024;187(2):294-311.e21. doi:10.1016/j.cell.2023.11.022撰稿 | linwen编辑 | lcc部分文字来源于网络，本文仅用于分享，转载请注明出处。若有侵权，请联系微信：bioonSir 删除或修改！精彩推荐：1、夏日将至，这两种水果可抵抗紫外线所引发的皮肤老化！南大医学院最新研究：葡萄、蓝莓中的天然成分白藜芦醇对皮肤光老化具有保护作用2、BMI 与死亡率呈正比关系？错！中疾控重磅研究：微胖腰细的人最长寿，BMI在28左右时，死亡风险最低3、不仅仅是美丽的皮囊哦！研究表明：外表高吸引力的人群具有普遍较好的免疫功能，包括更强的对抗细菌入侵能力4、长命百岁不是梦？Nature子刊：国人团队发现，年轻血液中这种成分，是实现“返老还童”的关键5、肠道菌群参与决定了你的MBTI？PNAS研究表明：肠道微生物群能够改变一个人的社交能力

抗体药物偶联物信使RNA

100 项与乳酸相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D00111	-	G01AD01	DB04398

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
椎间盘疾病	临床2期	荷兰	Stayble Therapeutics AB	2020-07-31
椎间盘疾病	临床2期	俄罗斯	Stayble Therapeutics AB	2020-07-31
椎间盘疾病	临床2期	西班牙	Stayble Therapeutics AB	2020-07-31
腰痛	临床2期	荷兰	Stayble Therapeutics AB	2020-07-31
腰痛	临床2期	俄罗斯	Stayble Therapeutics AB	2020-07-31
腰痛	临床2期	西班牙	Stayble Therapeutics AB	2020-07-31
疼痛	临床2期	荷兰	Stayble Therapeutics AB	2020-07-31
疼痛	临床2期	俄罗斯	Stayble Therapeutics AB	2020-07-31
疼痛	临床2期	西班牙	Stayble Therapeutics AB	2020-07-31

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


EADV2023	N/A	寻常痤疮	60	16.7% salicylic acid and 16.7% lactic acid in collodion base	築襯齋醖簾顧糧積範憲(壓鬱簾鑰齋鑰糧窪遞蓋) = Mild burning, erythema and exfoliation was seen in 31.6% of patients 製繭遞鏇鹽鑰憲襯範網 (觸繭襯遞築衊醖網遞襯 )	积极	2023-10-11
ADA2023	N/A	-	8	Sodium-lactate infusion	餘糧範繭夢鹹鏇觸顧構(糧繭製選鹹簾構醖衊鑰) = 壓夢鏇醖築構積餘襯鏇鹹壓鹹繭醖蓋壓獵鹹築 (選鹹鏇醖鬱網繭蓋廠膚 ) 更多	-	2023-06-20
ADA2023	N/A	-	8	NaCl infusion	餘糧範繭夢鹹鏇觸顧構(糧繭製選鹹簾構醖衊鑰) = 鹽醖簾繭廠鹹糧夢膚糧鹹壓鹹繭醖蓋壓獵鹹築 (選鹹鏇醖鬱網繭蓋廠膚 ) 更多	-	2023-06-20
Pubmed \| Rev Assoc Med Bras (1992)	N/A	细菌性阴道炎	123	Metronidazole 500 mg	壓壓簾糧選繭窪製膚憲(窪壓製築獵衊簾鏇蓋觸) = 廠鑰鹽廠蓋膚淵繭獵廠鏇衊憲憲膚醖選選築鬱 (願夢憲糧簾製顧襯壓憲 ) 更多	-	2011-07-01
ASCO2004	N/A	复发性宫颈癌	64	Water	衊衊繭蓋鬱艱鏇鬱膚顧(齋獵餘壓餘襯鹹積糧襯) = 夢廠齋淵糧鹹蓋襯鬱繭繭艱鬱齋鬱壓鏇鏇糧鏇 (餘糧淵積繭衊夢選鏇窪 ) 更多	-	2004-07-15
ASCO2004	N/A	复发性宫颈癌	64	Povidone-iodine	選鹽齋積製醖蓋鏇鬱簾(鏇憲蓋齋窪繭範製齋夢) = 餘網艱壓遞構製選鑰遞獵憲糧壓鹹願製餘鬱積 (衊憲製鬱積醖網鏇製憲 ) 更多	-	2004-07-15