BAAT

SINGAPORE, 12 May 2023 – By studying the unusual ability of bats to host viruses without significant illness, scientists at Duke-NUS Medical School have discovered a protein that could unlock new strategies for fighting inflammatory diseases in humans. “Bats have attracted great attention as a likely reservoir of the SARS-CoV-2 virus responsible for the COVID-19 pandemic,” said Professor Wang Lin-Fa, from Duke-NUS’ Emerging Infectious Diseases (EID) Programme, the senior author of the study published in the journal Cell. “But this unique ability to host yet survive viral infections could also have a very positive impact on human health if we can understand and exploit how they achieve this.” The research is focused on multi-protein complexes called inflammasomes that are responsible for the overactive inflammation that causes serious symptoms in many diseases. Inflammasomes are also implicated in functional decline in ageing. The Duke-NUS team discovered that a bat protein called ASC2 has a powerful ability to inhibit inflammasomes, thereby limiting inflammation. “This suggests that the high-level activity of ASC2 is a key mechanism by which bats keep inflammation under control, with implications for their long lifespan and unique status as a reservoir for viruses,” explained Dr Matae Ahn, first author and co-corresponding author of the study, who is an Adjunct Research Fellow with the EID Programme and the SingHealth Duke-NUS Medicine Academic Clinical Programme. Dr Ahn is also a full-time clinician in SingHealth’s Postgraduate Year One (PGY1) Residency Programme after graduating from Duke-NUS in 2022. Ms Vivian Chen, co-first author of the study and an MD-PhD candidate in Duke-NUS, highlighted that the team was able to demonstrate the potential for exploiting the powers of the bat protein in humans by showing it could also be effective in mice*. She elaborated, “Expression of the bat protein in genetically-modified mice dampened inflammation and reduced the severity of the diseases driven by various triggers, including viruses.” Examination of the ASC2 protein in detail identified four amino acids in the molecule that were key to making the bat protein more effective at dampening inflammation than its corresponding human protein. This provides valuable insight for the development of drugs that can mimic the anti-inflammatory effect of the bat protein. The next step for the team is to investigate the potential of their findings for treating humans. Prof Wang said: “We have filed patents based on this work and are exploring commercial partnerships for drug discovery. We are hoping to develop a new class of anti-inflammatory drugs for inflammasome-driven human diseases.” Prof Wang strongly believes that it is time to focus on the more promising aspects of what makes bats special “to help fight the human diseases of the future.” Duke-NUS’ Senior Vice-Dean for Research, Professor Patrick Casey, commented on the study, “Even as COVID-19 begins to recede from the public’s attention, Professor Wang and his team continue to break new ground with their basic research into bat biology, yielding unique insights that can potentially strengthen global pandemic preparedness. This is a prime example of the immense value basic scientific research brings to solving major public health challenges.” (Concept art representing the study and its findings developed by the study team) Flying in the starry night are our nocturnal and echo-locating bats, the only mammals capable of powered flight. The fire symbolises the inflammation driven by the activation of inflammasomes—multi-protein complexes that assemble inside cells in response to danger or microbial signals. Adaption to flight (a metabolically costly process) may have driven key changes in the bat's immune system that enable it to survive viral and other diseases that would kill other mammals. Among these key changes are differences in the highly expressed protein ASC2, a potent negative regulator of inflammasomes in bats and humans. In bats, however, the ASC2 protein has naturally evolved to dampen inflammation. This insight could lead to the development of novel therapeutics against inflammatory diseases. Credit: Qi Su * All work with laboratory animals in this study fully complied with policies and guidelines for the humane care and use of laboratory animals set forth by the Institutional Animal Care and Use Committee (IACUC). Reference: Ahn, M., Chen, V.C.W., Rozario, P., Ng, W.L., et al. 2023. Bat ASC2 suppresses inflammasomes and ameliorates inflammatory diseases. Cell. 2023; 186: 2144-2159.e22. DOI: 10.1016/j.cell.2023.03.036

VANCOUVER, BC, Aug. 24, 2023 /PRNewswire/ - Vice Health and Wellness Inc. (CSE: VICE) (FSE: Z24) (OTC Pink: VICFF) is excited to announce the signing of a Letter of Intent ("LOI") with Biologic Pharmamedical Research Ltd to initiate a collaborative product research and development partnership for weight-loss and obesity focused products. The purpose of the LOI is to express mutual interest in developing cutting-edge nutraceutical technology products that aim to revolutionize health categories through effective and science-based innovations. It is anticipated that this LOI will lead to the establishment of a definitive agreement outlining the specific terms, conditions, and responsibilities of both VICE and Biologic Pharmamedical. During the period of the LOI the Company has agreed to cover certain expenditures which are not to exceed $10,000. Biologic Pharmamedical Research, a trailblazer in the realm of pharmacology and natural therapeutic agents, will focus on mapping the pharmacology of natural therapeutic agents to better understand poly-pharmacology at the proteomic and genomic level. VICE is committed to enhancing people's lives by offering innovative and effective health products targeting weight-loss and obesity At the core of this partnership is THERMOGALLATE™, an exclusive and patent-pending technology fully owned by Biologic. It is a unique and ground-breaking technology that facilitates efficient fat metabolism and energy production. Unlike traditional keto-products, THERMOGALLATE™ capitalizes on the body's natural fat stores to induce ketogenesis, fostering sustainable weight management and heightened cognitive function. This technology triggers the activation of Brown Adipose Fat (BAT) and Hormone Sensitive Lipase (HSL), initiating a chain reaction that enhances fat burning and release for fuel. Through this innovative process, heat and energy are generated, reducing the reliance on physical exercise alone. The key reported benefits of THERMOGALLATE™ include: Activation of Brown Adipose Fat (BAT): Facilitates efficient fat burning. Initiation of Hormone Sensitive Lipase (HSL) Activity: Breaks down and mobilizes fat for energy. Induction of Ketogenesis: Offers an alternate brain fuel source during low-caloric intake. Enhanced Energy and Cognitive Performance: Elevates energy levels, creativity, and cognitive function. Reduced Hunger Cravings and Dietary Control: Supports appetite management and dietary adherence. The partnership will encompass the creation of products with Thermogallate™ that contribute to improved lean body mass to fat mass proportions beginning with the research and development of a Gummy Version. Biologic Pharmamedical will explore the possibilities of a gummy version of the Brown Adipose Tissue activator, catering to consumers seeking a delightful and enjoyable means of experiencing the potential health benefits of the product. The company plans to explore further uses of Thermogalallate™ in consumer health products. Biologic Pharmamedical will play a crucial role in supporting the marketing efforts for these Nutraceutical Technology products. Biologic Pharmamedical will provide scientific backing, literature, and relevant research findings to substantiate health claims associated with the products. Furthermore, Biologic Pharmamedical will assist Vice Health and Wellness in organizing digital seminars or speaking engagements to disseminate vital information about the products. In addition, Vice Health and Wellness supplements will be enriched with Glyvia™, a patented and Health Canada approved natural product. Glyvia™ presents a plant-based, zero-calorie sweetness that emulates the flavor of sugar without the commonly associated bitter aftertaste found in alternative sweeteners like stevia. This proprietary complex, composed of aminoacetic acid and plant glycosides, enhances mouthfeel, sweetness, and sweet/sour balance, delivering an appealing and satisfying sensory experience. Maciej Lis, Chief Executive Officer of Vice, stated, "The collaboration between Biologic Pharmamedical Research and Vice holds tremendous potential and aligns with our shared goals of promoting health and wellness to help consumers achieve the pursuit of optimal wellness. We are excited about the possibilities and eagerly look forward to further discussions and negotiations to formalize this partnership." Franco Cavaleri BSc PhDc, Founder and CEO of Biologic, noted, "We're thrilled to partner with VICE's like-minded team to tackle weight loss and obesity through our advanced technologies led by THERMOGALLATE™. This patented technology, dubbed the 'Natural GLP1 agonist and Brown Fat Thermogenic inducer,' aims to regulate blood glucose and activate fat metabolism. This leads to spontaneous weight management and increased energy by revitalizing the body's natural fat-utilizing systems. For further information and updates, please visit the newly updated investor website at About Biologic Pharmamedical Research Biologic Pharmamedical Research is dedicated to cutting-edge research and development in the health and wellness industry. The company focuses on mapping the pharmacology of natural therapeutic agents to engineer more reliable and efficacious outcomes for consumers. About Vice Health and Wellness Inc. Vice Health and Wellness Inc. is a dynamic publicly traded company dedicated to fostering healthier lifestyle choices by offering a diverse range of products that empower consumers to enhance their mental and physical well-being. As an ever-growing community of like-minded individuals and organizations, we believe in the power of collective small steps leading to remarkable transformations. Our product line features low-sugar, plant-based gummy products, and we are actively spearheading innovations in alignment with emerging trends in the health and wellness sector. By prioritizing weight loss and harnessing the potential of AI-powered health and wellness applications, which leverage state-of-the-art artificial intelligence algorithms, we aim to provide individuals with unparalleled advice, personalized recommendations, unwavering support, and transformative solutions on their journey to ultimate well-being. Our exceptional applications intend to offer a multitude of treatment benefits, empowering users to embark on a transformative path toward optimal health. Neither the Canadian Securities Exchange nor its Regulation Services Provider (as that term is defined in the policies of the Canadian Securities Exchange) accepts responsibility for the adequacy or accuracy of this release. Forward Looking Statements Certain information set forth in this news release may contain forward-looking statements that involve substantial known and unknown risks and uncertainties. All statements other than statements of historical fact are forward-looking statements, including, without limitation, statements regarding future financial position, business strategy, use of proceeds, corporate vision, proposed acquisitions, partnerships, joint- ventures and strategic alliances and co-operations, budgets, cost and plans and objectives of or involving the Company. Such forward-looking information reflects management's current beliefs and is based on information currently available to management. Often, but not always, forward-looking statements can be identified by the use of words such as "plans", "expects", "is expected", "budget", "scheduled", "estimates", "forecasts", "predicts", "intends", "targets", "aims", "anticipates" or "believes" or variations (including negative variations) of such words and phrases or may be identified by statements to the effect that certain actions "may", "could", "should", "would", "might" or "will" be taken, occur or be achieved. A number of known and unknown risks, uncertainties and other factors may cause the actual results or performance to materially differ from any future results or performance expressed or implied by the forward-looking information. These forward-looking statements are subject to numerous risks and uncertainties, certain of which are beyond the control of the Company including, but not limited to, the impact of general economic conditions, industry conditions and dependence upon regulatory approvals. Readers are cautioned that the assumptions used in the preparation of such information, although considered reasonable at the time of preparation, may prove to be imprecise and, as such, undue reliance should not be placed on forward- looking statements. The Company does not assume any obligation to update or revise its forward-looking statements, whether as a result of new information, future events, or otherwise, except as required by securities laws. SOURCE Vice Health And Wellness Inc.

癌症-世纪难题！发生肿瘤-凉ban？凉“办”！ 未尝不可！2022年8月3日Nature在线发表由瑞典卡罗林斯卡医学院和中国复旦大学团队合作的题为《Brown-fat-mediated tumour suppression by cold-altered global metabolism》的研究，其中验证了多种癌症小鼠模型和一例癌症病人。研究表明，低温可以抑制肿瘤生长，激活棕色脂肪（BAT）及UCP1是其关键机制。恶性肿瘤被认为是代谢性紊乱，大部分实体瘤都加速糖酵解代谢攫取能量，即Warburg效应。为了研究产热相关的代谢对肿瘤的作用。作者把皮下植入结肠癌的C57BL/6小鼠，放在4℃和30℃两种温度下，观察肿瘤的生长。结果发现，20天后肿瘤生长竟相差约80%。不仅这一种肿瘤，在纤维肉瘤、乳腺癌、黑色素瘤和胰腺癌多种癌症中均有“奇效”。不仅移植肿瘤模型有效，不同基因背景的自发肿瘤也有效。在低温面前，这些肿瘤细胞的生长曲线变得不再嚣张，荷瘤小鼠的生存率翻倍。免疫组化分析肿瘤微环境（TME）发现CD31+的肿瘤微血管和Ki-67标志的肿瘤细胞增殖速率显著下降，CD45+髓细胞下降。而肿瘤巨噬细胞和成纤维细胞以及细胞凋亡未发生变化。因此，证明冷处理显著抑肿瘤，改变TME。作用机制？在皮下肿瘤模型中，冷处理或许能通过局部降温抑制肿瘤生长。虽然自发肠癌模型基本排除了这种可能，但是作者还是拿肝脏做了实验，毕竟肝脏也是肠癌常常扩散的器官。把肠癌细胞移植入肝，冷暴露依然能显著抑制其生长。作者还检测了皮下、内器官和肿瘤组织的温度，结果显示4℃和30℃条件下并无差异。不仅如此，在4℃下肛门测得的核心体温还是略有增加的。由此低温接触对抑制肿瘤生长的途径，排除。低温下，健康或荷瘤小鼠BAT结构致密程度增加，呈现更小多室结构，这是BAT激活的典型特征。与此表型一致，BAT的COX4+的线粒体和CD31+的微血管也显著增加。UCP1蛋白表达一致性升高。说明瘤移植未影响低温诱导的BAT激活。并且，在移植和自发肿瘤模型中，免疫组化分析发现了典型的白色脂肪（WAT）棕色化表型，包括脂肪细胞更小、胞内多泡结构、线粒体增加、微血管数目增多和UCP1蛋白表达增加，说明也没有干扰到低温激活的WAT棕色化。接下来通过PET-CT成像分析了荷瘤小鼠多种器官的氟脱氧葡萄糖18F-FDG摄入。结果发现冷处理富集葡萄糖于肩胛BAT而导致肿瘤组织几乎断供，换言之，低温通过增多BAT葡萄糖摄入而减少了肿瘤的摄入。为了确认BAT的作用，作者干脆一刀切除BAT。结果这一刀几乎抵消了低温对肿瘤的抑制作用。低温下肿瘤葡萄糖摄入水平的下降也被完全逆转，低氧、血管化和肿瘤细胞增殖也得到改善。相比之下，热中性条件下，BAT切除对肿瘤生长并无作用。由此低温诱导的肿瘤生长主要依赖于BAT。肿瘤代谢改变？基因组和蛋白组学分析发现低温下肿瘤的糖脂代谢被削弱，相关信号通路被抑制，葡萄糖摄入的关键蛋白GLUT显著下调，包括Glut1、Glut4和Glut7。PI3K、AKT和mTOR信号通路也被显著抑制。相反，BAT糖酵解增强，其相关信号通路上调，Glut4和糖酵解相关基因上调。证实了冷暴露通过抑制糖酵解重塑了肿瘤代谢。肿瘤与BAT竞争摄糖是低温抑瘤的关键？作者引入了高糖饮食。热中性条件下，饮水中提高葡萄糖浓度导致肿瘤生长加速，浓度15%时作用最大，甚至抵消了冷暴露对肿瘤的抑制作用。温度改变并未影响肿瘤细胞增殖、缺氧状态、炎症和微血管密度。在黑色素瘤和胰腺癌中也复现了高糖抵消低温抑瘤作用的结果。在分子水平上，Glut1基因和蛋白表达增加、PI3K和AKT磷酸化激活增加也印证了上述结果。因此BAT增加葡萄糖摄入导致肿瘤缺糖是肿瘤抑制的重要机制。UCP1是脂肪组织产热的关键线粒体蛋白。在冷暴露下野生鼠体重显著下降，而Ucp1敲除鼠则没有这种减重作用，也观察不到肿瘤抑制。与此一致的是，UCP1敲除也显著减少了产热。APET-CT扫描分析显示BAT葡萄糖摄入不明显，肿瘤的葡萄糖摄入也没有受到影响。肿瘤、BAT和sWAT大小在Ucp1敲除后也没有改变。因此UCP1是调控肿瘤抑制的重要蛋白。以上虽然运用了多种动物模型，但在人身上是否有效？作者招募了6位健康志愿者（3男3女22-25岁），穿轻薄的衣服每天在16℃的环境中2-6小时，连续14天。PET扫描显示无论男女在两侧锁骨、肩颈和胸骨区域的BAT显著激活。18F-FDG分析显示成年人体中BAT存量可观，并在低温耐受中被激活。接下来针对18岁霍奇金淋巴瘤病人进行了研究，让其接受了22℃ 7天轻度的冷暴露。PET-CT扫描分析显示锁骨、肩颈和胸骨区域大量的BAT和葡萄糖摄入增加。而28℃复温4天后糖摄入和BAT激活显著下降。CT扫描分析确认了淋巴瘤仍然存在。该前瞻性研究证明：（1）成年人中存在大量的BAT；（2）轻度低温耐受葡萄糖摄入增加，BAT激活；（3）在肿瘤病人中低温暴露也能激活BAT；（4）肿瘤病人暴露于轻度的低温即可显著的降低肿瘤葡萄糖摄入。总之，虽然需要更严谨的临床研究证明，但已经看到了该研究临床应用更多的可行性。原文：https://doi.org/10.1038/s41586-022-05030-3解读者注：本文阐释了一种肿瘤治疗的新理念，把BAT摄糖产热作为控制肿瘤生长阀门的一个齿轮。这是抗癌研究的一个重大突破，无副作用，性价比超高。冻一冻，“冷静”一下就可抗癌，这对不断化疗，掉光了头发，花掉了家底的癌症患者而言无疑是莫大喜讯。癌症研究历来是个无底洞，癌细胞靶点复杂而多变，尤其是实体瘤。虽然CAR-T在血液系统癌症中大有完胜的战绩，但实体瘤仍未呈现破防态势。不断加靶的CAR-X（T\NK\M）、溶瘤病毒跃跃欲试。但其实除了更加精准和靶向，既然癌细胞是细胞增殖道场里失控的黑马，相比杀死黑马，白马（健康细胞）也荡然无存的策略（比如：化疗）来说，降低其活跃程度或许是更友好的策略。代谢调控方向的大招就更普世。早在2012年，浙江大学胡汛教授团队就在eLife上发表对40位中晚期肝癌患者进行“饥饿疗法”实验，结果发现，患者的累计中位生存期超过3年半（原先按临床数据来看仅半年）。然而并不是说几天不吃饭就能“饿死”癌细胞。对于那些试图通过不吃饭、减少营养摄入等方法来“饿死癌细胞”的，中国医学科学院肿瘤医院综合科副主任丛明华更是直接表示：“肿瘤是饿不死的，饿死的最后一定是人！”该疗法需要在先进影像设备引导下精准注射栓塞剂，“堵”住肿瘤动脉，同时联合灌注化疗，才可 “饿死”癌细胞。而本文“冻死”癌细胞却是真正的冻冻就行。本文通过多种肿瘤动物模型及健康和癌症患者的研究，证明了低温（4℃即可，这不就是北方冬天的气候吗）抑制荷瘤小鼠的肿瘤生长，抑制程度甚至与大多数抗癌药物相当。在人体轻度降温22℃即可观察到响应。这种治疗手段简便易行、成本低廉，广谱抗癌，真是居家旅行（医院）的抗癌良策。按常理寒冷条件下产热是增加的。文中荷瘤小鼠的代谢确有增加，所有荷瘤小鼠低温下的空腹血糖水平下降，葡萄糖耐受和胰岛素敏感性也提高。该策略成功的关键就在于在葡萄糖有限的条件下，BAT强势激活优先占用，导致肿瘤细胞断供。这么说来低温这种策略也是很偏心的，一边拱火系统代谢，一边撺掇BAT占住有限资源，挤兑肿瘤细胞，“白马”完胜。由此几点提示（1）低温也是具有选择性的，（2）与“饥饿疗法”殊途同归，（3）低糖饮食是低温抗癌的前提。另外，其他激活BAT的措施是否也有同效，UCP1可否作为药物靶点？低温是如何激活的BAT？未知拼图有待揭示。该文为抗癌策略的研究提供了新的视角，貌似大战终于找到了一个缺口，值得学习和思考。