作者: Baig, Mirza Muhammad Faran Ashraf ; Saleem, Ammara ; Shah, Shahid ; Alshammari, Abdulrahman ; Albekairi, Norah A ; Hussain, Liaqat ; Moazzam, Anam ; Akhtar, Muhammad Furqan

Presently, it is known that the progression of obesity concomitantly leads to polycystic ovary syndrome and infertility. This study aimed to evaluate the potential effects of metformin (M; insulin secretagogues) and gliclazide (G; insulin sensitizer) alone and their combination at different doses to treat obesity-induced PCOS. High high-fat diet was given to all female Wistar rats for nine weeks to induce obesity except for the normal control group which received a normal chow diet. Estradiol valerate (0.8 mg/kg) was also given to all obese rats to induce polycystic ovarian syndrome. After the induction, M (100, 300 mg/kg) and G (5, 10 mg/kg) were given orally either individually or in combination for 28 days. The notable (p < 0.0001) reduction in body weight and blood glucose level was observed in treatment groups in contrast to disease control (DCG). The marked (p < 0.05-0.0001) decrease in hemocylated hemoglobin, serum insulin, cholesterol, triglycerides, and testosterone was observed in treated groups, notably in combination groups (M100+G10 mg/kg) in contrast to DCG. There was a considerable (p < 0.01-0.0001) increase in progesterone E2, estradiol, luteinizing, and follicle-stimulating hormones in treated groups as compared to DCG. Treatment with M and G treated groups also exhibited marked (p < 0.05-0.0001) increases in SOD, CAT, and GSH while decreased in NO and MDA levels in ovary tissue as evidenced by the histological study of the ovary. Treatment with M and G alone and in combination significantly (p < 0.0001) restored the serum IL-6, NrF2, and NF-κB levels as compared to DCG. The results inveterate that the M and G combination (M100+G10, and M300+G10) was useful in treating obesity-induced infertility due to antioxidant properties, hypolipidemic effects, and modulation of inflammatory markers.

2022-06-01·animal

Effects of magnolol and honokiol blend on performance, egg quality, hepatic lipid metabolism, and intestinal morphology of hens at late laying cycle

Article

作者: Wei, Jintao ; Zhao, Na ; Zhang, Hao ; Fan, Qiwen ; Huang, Shaowen ; Guo, Wanzheng ; Chen, Fang ; Jin, Feng ; Du, Encun

Magnolol and its isomer honokiol are polyphenols with anti-oxidative and anti-inflammatory activities. We evaluated the effects of magnolol and honokiol supplementation alone or in combination with hen diets during the late laying cycle. A total of 540 Jingfen pink-shell laying hens (50 weeks old) were randomly assigned to six treatments: a control diet and diets supplemented with 300 mg/kg magnolol (M₃₀₀), honokiol (H₃₀₀), or 300 mg/kg total phenols with a magnolol/honokiol ratio of 2:1 (M₂₀₀H₁₀₀), 1:2 (M₁₀₀H₂₀₀), and 1:1 (M₁₅₀H₁₅₀). Compared with that of the control, all supplementation groups had higher laying rates and the M₃₀₀, M₁₀₀H₂₀₀, and M₁₅₀H₁₅₀ groups showed comparatively lower feed conversion ratios. Magnolol and honokiol supplementation increased the Haugh units of fresh eggs at week 62 and alleviated the decline of the Haugh units of eggs stored for 14 days. Compared with that of the control group, the serum total antioxidant capacity of the M₁₀₀H₂₀₀ and M₁₅₀H₁₅₀ groups significantly increased, and all supplementation groups had higher total antioxidant capacity and lower malondialdehyde content in the liver. With respect to lipid metabolism, the M₂₀₀H₁₀₀ and M₁₅₀H₁₅₀ groups had lower total and relative liver weights compared with those of the control and H₃₀₀ groups. The mRNA expression levels of CCAAT enhancer binding protein alpha, sterol regulatory element binding protein-1, fatty acid synthase and stearyl coenzyme A desaturase 1 involved in lipogenesis; microsomal triglyceride transfer protein and apolipoprotein B involved in fatty acid transport; and the proinflammatory cytokine interleukin-1 beta were lower in all supplementation groups compared with those in the control. With respect to gut health, the heights of the jejunum and ileum villi significantly increased in all supplementation groups compared with those of the control, and the jejunum villus heights of the M₃₀₀ and M₁₅₀H₁₅₀ groups were higher than those of the H₃₀₀ and M₁₀₀H₂₀₀ groups. The H₃₀₀ and M₁₅₀H₁₅₀ groups had higher mRNA expression levels of zonula occludens-1 in the ileum compared with those in the control and M₃₀₀ groups, whereas all supplementation groups had higher mRNA levels of claudin-1 than that of the control group. In conclusion, magnolol and honokiol improved hen performance and the albumen quality of fresh and stored eggs by improving the antioxidant capacity, liver lipid metabolism, and intestinal health of laying hens. The combination of magnolol and honokiol at a 1:1 ratio may be an optimal choice for hen diet supplementation.

2021-02-01·Poultry Science2区 · 农林科学

Effects of magnolol on egg production, egg quality, antioxidant capacity, and intestinal health of laying hens in the late phase of the laying cycle

2区 · 农林科学

ArticleOA

作者: Zhang, Hao ; Wei, Jintao ; Huang, Shaowen ; Jin, Feng ; Fan, Qiwen ; Zheng, Chao ; Guo, Wanzheng ; Chen, Fang ; Du, Encun ; Zhang, Wei ; Zhao, Na

Magnolol is a multifunctional plant polyphenol. To evaluate the effects of magnolol on laying hens in the late laying period, 360 (50-week-old) laying hens were randomly assigned to 4 dietary treatments: a non-supplemented control diet (C), and control diets supplemented with 100, 200, and 300 mg/kg of magnolol (M100, M200, and M300), respectively. Each treatment had 6 replicates with 15 hens per replicate. Results showed that dietary supplementation of 200 and 300 mg/kg of magnolol increased the laying rate and the M200 group had a lower feed conversion ratio (P < 0.05). Magnolol supplementation (200 and 300 mg/kg) could linearly increase albumen height and Haugh unit of fresh eggs in the late phase of the laying cycle (P < 0.01). And magnolol linearly alleviated the decline of the albumen height and Haugh unit of eggs stored for 14 d (P < 0.01). The total superoxide dismutase activity in the ovaries of M100 group was greater than that in the other treatments (P < 0.05). As dietary magnolol levels increased, villus height of jejunum and ileum linearly increased (P < 0.01). M200 and M300 groups had higher expression level of occludin in the ileum compared with group C (P < 0.01). The level of nitric oxide production and inducible nitric oxide synthase expression in the ileum of M200 group were lower than that in the C group (P < 0.05). In conclusion, dietary supplementation of 200 and 300 mg/kg magnolol can improve hen performance, albumen quality of fresh and storage eggs, and hepatic lipid metabolism in the late laying cycle. Also, magnolol has a good effect on increasing villi and improving the intestinal mucosal mechanical barrier function.

项与 M-300 相关的新闻（医药）

2024-04-15

·药时代

AACR之后，又会有多少BD交易产生？

当地时间2024年4月8日，在美国癌症研究协会（AACR）年会会场外，数百名参会者佩戴着偏光纸质眼镜，站在庞大的圣地亚哥会议中心前，观看日食。虽然时间只有短短几分钟，但这样小插曲使原本热烈的会议气氛更加活络，今年的AACR在参会人数与壁报数量两个方面均破记录。摄影：（Annalee Armstrong/Fierce Biotech）时至今日，距离2024AACR年会结束已有近一周时间，远行的中国从业者们也尽数返航。对于他们而言，AACR的意义每年都不太一样，从起初观看前沿技术转化，license-in或者follow，到如今向友商展示自家实力，等待BD和投资青睐。那么一场两万多人的国际会议，不仅成为了中外药企沟通的桥梁，更是成为了全球医药行业演变的一个缩影。据不完全统计，2024年AACR有80家中国药企披露摘要，相较于2023年70家，同比增长14.29%。其中，以康源博创、多禧生物、恒瑞医药、海创药业等多家药企披露产品数量最多。生物药研发方面，依旧是以ADC和多抗作为主力军。（毕竟这也是本土药药企的出海主力军）2023年，创新药投资处在下行通道，二级市场上市公司表现弱于大盘，祸不单行一级市场同样不容乐观。据不完全统计，2023年全球创新药投资事件991起，较2022年的1132起下降12.45%，已回落至2019年水平。在“资本寒冬”的背景下，众多Biotech或迫于运营压力，或迫于投资人的千叮万嘱等多重因素，BD成了件“头等大事”。得益于此，2023年成为我国创新药出海元年。默沙东接连入手科伦博泰7款ADC；BMS以8亿美元首付款，84亿美元交易总价入手百利天恒的双抗ADC，刷新了我国创新药单笔出海记录……在MNC对我国创新药广泛认可的前提条件下，2024AACR年会之后，又会有多少BD交易产生？首先是ADC篇。据不完全统计，本次AACR共有58款国产ADC产品报道摘要，涉及药企29家。数据来源：医药笔记其中，恒瑞的SHR4602（HER2）、多禧的DXC126-262（HER2）、启德的GQ1005（HER2）等多款HER2 ADC已推至临床阶段。而HER2、TROP2、FRα一直作为ADC的研发热点，如何脱颖而出，至关重要。一位行业专家以SHR4602为例，该产品的定位在DS-8201或SHR-A1811（恒瑞DS-8201的快跟产品）耐药的后线治疗，具有差异化优势。再者，便是百利天恒84亿美元交易之后，更加热闹的双抗ADC领域。进展最快的除百利天恒的BL-B01D（HER3/EGFR）外，康宁杰瑞的HER2双表位ADCJSKN003也已进入临床三期阶段，谁将成为我国首款获批的双抗ADC，值得期待。与此同时，信达的IBI3001（B7-H3/EGFR）、多禧生物的（ Trop2/EGFR）、百奥赛图的BCG016（5T4 / MUC1）、橙帆的VBC101-F11（EGFRcMet）等多款产品均值得关注。今年3月，百利天恒宣布已收到8亿美元首付款，实打实的真金白银，刺激着每一个双抗ADC玩家的神经。再者便是单抗、多抗篇。此类产品相较于双抗ADC、ADC对MNC的吸引力有限，2022年以50亿美元买下康方AK112（PD-1/VEGF）的Summit，彼时还名不见经传。数据来源：医药笔记据不完全统计，全球范围内，已上市的双抗有10款，安进、罗氏、康方、强生等药企走在前列。一位业内人士告诉药时代，他对PD-1和TIGIT的双特异性抗体十分在意。这类抗体的设计使其可以同时靶向两个免疫抑制点，从而更有效地激活免疫系统，增强对肿瘤细胞的攻击。国外进展较快的有罗氏、阿斯利康两大玩家。国内布局最快的是信达的IBI321，泽璟的ZG005、普米斯的PM1022、圣和的SH006、复宏汉霖的HLX301紧跟其后。此外，在今年的AACR年会上，辉瑞/Mestag Therapeutics的M300与Kyowa Kirin的KK2260值得关注。M300是“FIC”的FAP-LTβR双特异性抗体，该靶点通过诱导三级淋巴组织的形成发挥抑癌作用，作为抗癌治疗的新靶点，与PD-L1抗体联用展现出强劲的抗肿瘤疗效。至于，KK2260为TfR1×EGFR双抗，针对EGFR高表达癌症，作为新设计，由于其在脑内皮细胞中高表达，可开发TfR1双特异性抗体提高药物跨血脑屏障的能力，为本土双抗玩家提供新思路。最后便是小分子方面，KRAS靶向药物领域尤为瞩目。KRAS G12C只是其中的冰山一角，其他KRAS突变（如G12D和G12V）等具有巨大潜力，像贝达的BPI-501836、恒瑞的SHR1127、劲方的GFH375、泰励的TSN1611均是靶向KRAS G12D。其他方面，以同宜医药的双配体BET-PROTAC药物CBP-8008为代表的各类配体偶联PROTAC前沿技术；以AI、ML、Slush用于药物发现的研究也成为一大卖点，特别是在有条件，且内卷的当下。参考资料：1.AACR: Oncologists look to the skies as partial solar eclipse passes over San Diego（fiercebiotech）2.aacr官网3.2024AACR会议小结：百花齐放 ADC、双抗、免疫联合盘点368（IO笔记）4.2024 AACR新药开发机会分析（医药魔方数据库）5.其他公开资料封面图来源：pixabay版权声明/免责声明本文为原创文章。本文仅作信息交流之目的，不提供任何商用、医用、投资用建议。文中图片、视频、字体、音乐等素材或为药时代购买的授权正版作品，或来自微信公共图片库，或取自公司官网/网络，部分素材根据CC0协议使用，版权归拥有者，药时代尽力注明来源。如有任何问题，请与我们联系。衷心感谢!药时代官方网站:www.drugtimes.cn联系方式:电话:13651980212微信:27674131邮箱:contact@drugtimes.cn夹在“见死不救”与“画饼充饥”之间的肿瘤学药物加速批准狂风过境，中国药企的出海浪潮将止步于此？最长三月打一针，所有关键疗效终点均显著！梯瓦公布偏头痛创新药在华III期研究结果！点击阅读原文，了解更多！

AACR会议抗体药物偶联物临床3期引进/卖出

2024-04-09

·GlobeNewswire-Health Care

Mestag Presents Preclinical Data at AACR on its M300 Program, a Conditionally Active LTBR Agonist Designed to Induce Tertiary Lymphoid Structures in Tumors

April 08, 2024 -- Mestag Therapeutics (“Mestag”), a biotech company harnessing new insights into fibroblast-immune interactions, is today presenting data on its M300 program in a late-breaking poster session at the 2024 American Association for Cancer Research (AACR) meeting. The poster titled “Conditionally active, therapeutic lymphotoxin beta receptor (LTBR) agonist bispecific antibodies for induction of tertiary lymphoid structures in the treatment of solid tumors” is being presented as part of the “Late-Breaking Research: Immunology 2” poster session (9:00 a.m. – 12:30 p.m. PT, poster section 52; board number 11). The presented data demonstrate that Mestag’s bispecific antibody co-engages fibroblast activated protein (FAP) and LTBR to conditionally activate LTBR and induce Tertiary Lymphoid Structures (TLS) in the tumor. In vivo data showed potent monotherapy efficacy as well as tumor regression in combination with tumor antigen or a checkpoint inhibitor. Ray Jupp, PhD, Chief Scientific Officer of Mestag Therapeutics, said, “TLS is an exciting new area of anti-cancer immunology. There is now extensive evidence that the presence of these structures plays a critical role in anti-tumor immunity and better survival outcomes in patients. We are excited to share that M300 conditionally induces TLS formation in hard-to-treat tumor models representative of low antigen, cold human tumors, an area of significant unmet need. We look forward to bringing this to patients as soon as possible.” M300 is a first-in-class bispecific antibody designed to conditionally induce the formation of Tertiary Lymphoid Structures (TLS) in solid tumors. TLS are aggregates of immune cells that can form in tumor tissue as part of our bodies’ natural anti-cancer mechanisms, and drive powerful immune responses by recruiting, educating, and activating new anti-tumor T and B-cells. Fibroblast populations play a key role in the induction and maintenance of TLSs. TLSs in tumors are strongly predictive of both improved patient outcomes across solid tumor types and better response to therapy. Mestag harnesses new insights into fibroblast-immune interactions to develop impactful treatments for patients with cancer and inflammatory diseases. We are progressing a pipeline of sophisticated first-in-class antibodies designed to direct and drive the immune system using known and emerging fibroblast-immune biology for a distinctly differentiated class of therapeutics. Our pipeline comprises the M300 program, leveraging new understanding of tertiary lymphoid structures (TLS) in solid tumors, and their role in driving improved patient outcomes; the M402 program, targeting a stromal checkpoint to dampen down the activation of specific immune cell subsets in inflammatory disease; and earlier programs in discovery stage. Separately, in a collaboration with Janssen Biotech, Inc., a Johnson & Johnson company, we are also identifying novel targets for future therapies. Our founding investigators comprise global experts in inflammatory disease, cancer, computational biology and fibroblast biology from the University of Oxford, Brigham & Women’s Hospital, Harvard Medical School and Cold Spring Harbor Laboratory. We are supported by leading life science investors SV Health Investors, Johnson & Johnson Innovation – JJDC, Inc., Forbion, GV (formerly Google Ventures) and Northpond Ventures. Mestag is headquartered in Cambridge, UK, and in 2021 was recognized on the Fierce 15 list of innovative biotechnology companies. The content above comes from the network. if any infringement, please contact us to modify.

免疫疗法AACR会议

2024-03-05

·GlobeNewswire-Health Care

Mestag Therapeutics’ M300 Program, Designed to Conditionally Induce Tertiary Lymphoid Structures in Tumors, Selected for Late-Breaking Poster Presentation at AACR Annual Meeting

CAMBRIDGE, United Kingdom, March 05, 2024 (GLOBE NEWSWIRE) -- Mestag Therapeutics (“Mestag”), a biotech company harnessing new insights into fibroblast-immune interactions to develop impactful treatments for patients, today announced the acceptance of a late-breaking abstract titled “Conditionally active, therapeutic lymphotoxin beta receptor (LTBR) agonist bispecific antibodies for induction of tertiary lymphoid structures in the treatment of solid tumors” for presentation at the American Association for Cancer Research (AACR) meeting taking place April 5-10, 2024 in San Diego, CA. Presentation details: Poster Title:Conditionally active, therapeutic lymphotoxin beta receptor (LTBR) agonist bispecific antibodies for induction of tertiary lymphoid structures in the treatment of solid tumorsAbstract Number:LB123Date:April 8, 2024Time:9:00 a.m. – 12:30 p.m. PTSession Title:Late-Breaking Research: Immunology 2Location:Poster section 52; Poster board number 11 Late-breaking abstract titles are currently available on AACR’s online itinerary planner, and late-breaking abstract text will be available on AACR’s planner on April 5, 2024, at 12:00 p.m. PT. The planner can be accessed at: https://www.abstractsonline.com/pp8/#!/20272. About Mestag’s M300 Program M300 is a first-in-class antibody program designed to conditionally induce the formation of Tertiary Lymphoid Structures (TLS) in the tumor. TLSs are aggregates of immune cells that form in tumor tissue as part of our bodies’ natural anti-cancer mechanisms, and drive powerful immune responses by recruiting, educating, and activating new anti-tumor T and B-cells. Fibroblast populations play a key role in the induction and maintenance of TLSs. TLSs in tumors are strongly predictive of both improved patient outcomes across solid tumor types and better response to therapy. About Mestag Therapeutics Mestag harnesses new insights into fibroblast-immune interactions to develop impactful treatments for patients with cancer and inflammatory diseases. We are progressing a pipeline of sophisticated first-in-class antibodies designed to direct and drive the immune system using known and emerging fibroblast-immune biology for a distinctly differentiated class of therapeutics. Our pipeline comprises the M300 program, leveraging new understanding of tertiary lymphoid structures (TLS) in solid tumors, and their role in driving improved patient outcomes; the M402 program, targeting a stromal checkpoint to dampen down the activation of specific immune cell subsets in inflammatory disease; and earlier programs in discovery stage. Separately, in a collaboration with our partner Janssen Biotech, Inc., a Johnson & Johnson company, we are also identifying novel targets for future therapies. Our founding investigators comprise global experts in inflammatory disease, cancer, computational biology and fibroblast biology from the University of Oxford, Brigham & Women’s Hospital, Harvard Medical School and Cold Spring Harbor Laboratory. We are supported by leading life science investors SV Health Investors, Johnson & Johnson Innovation – JJDC, Inc., Forbion, GV (formerly Google Ventures) and Northpond Ventures. Mestag is headquartered in Cambridge, UK, and in 2021 was recognized on the Fierce 15 list of innovative biotechnology companies. For further information please visit our website www.mestagtherapeutics.com For enquiries, please contact: InvestorsAlexandra Santosasantos@wheelhouselsa.comMediaAljanae Reynoldsareynolds@wheelhouselsa.com

AACR会议免疫疗法临床研究

100 项与 M-300 相关的药物交易

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