Exposure of many cancer cells, including multiple myeloma cells, to cytotoxic concentrations of natural products celastrol and withaferin A or synthetic compounds of the IHSF series resulted in denaturation of a luciferase reporter protein. Proteomic analysis of detergent-insoluble extract fractions from HeLa-derived cells revealed that withaferin A, IHSF058 and IHSF115 caused denaturation of 915, 722 and 991 of 5132 detected cellular proteins, respectively, of which 440 were targeted by all three compounds. Western blots showed that important fractions of these proteins, in some cases approaching half of total protein amounts, unfolded. Relatively indiscriminate covalent modification of target proteins was observed; 1178 different proteins were modified by IHSF058. Further illustrating the depth of the induced proteostasis crisis, only 13% of these proteins detectably aggregated, and 79% of the proteins that aggregated were not targets of covalent modification. Numerous proteostasis network components were modified and/or found in aggregates. Proteostasis disruption caused by the study compounds may be more profound than that mediated by proteasome inhibitors. The compounds act by a different mechanism that may be less susceptible to resistance development. Multiple myeloma cells were particularly sensitive to the compounds. Development of an additional proteostasis-disrupting therapy of multiple myeloma is suggested.

2018-08-15·Journal of virology2区 · 医学

Immunization by Replication-Competent Controlled Herpesvirus Vectors

2区 · 医学

Article

作者: Feller, Joyce ; Bloom, David C. ; Tran, Robert K. ; Voellmy, Richard

We hypothesized that vigorous replication of a pathogen may be critical for eliciting the most potent and balanced immune response against it. Hence, attenuation/inactivation (as in conventional vaccines) should be avoided. Instead, the necessary safety should be provided by placing replication of the pathogen under stringent control and by activating time-limited replication of the pathogen strictly in an administration region in which pathology cannot develop. Immunization will then occur in the context of highly efficient pathogen replication and uncompromised safety. We found that localized activation in mice of efficient but limited replication of a replication-competent controlled herpesvirus vector resulted in a greatly enhanced immune response to the virus or an expressed heterologous antigen. This finding supports the above-mentioned hypothesis and suggests that the vectors may be promising novel agents worth exploring for the prevention/mitigation of infectious diseases for which efficient vaccination is lacking, in particular in immunocompromised patients.

2018-07-01·Cell stress & chaperones3区 · 生物学

Targeted heat activation of HSP promoters in the skin of mammalian animals and humans

3区 · 生物学

Article

作者: Voellmy, Richard ; de Viragh, Pierre A ; Zürcher, Olivier ; Zürcher, Manon ; Roberts, Stephen M ; Hall, Alexis K

The use of highly inducible HSP promoters for exerting spatial and/or temporal control over the expression of therapeutic transgenes has long been discussed. Localized and time-limited induction of the heat shock response may potentially also be of medical interest. However, such applications would require targeted delivery of heat doses capable of activating HSP promoters in tissues or organs of interest. Accessible areas, including the skin and tissues immediately underneath it, may be most readily targeted. A few applications for heat-directed or heat-controlled therapy in the skin might involve expression of proteins to restore or protect normal skin function, protein antigens for vaccination/immunotherapy, vaccine viruses or even systemically active proteins, e.g., cytokines and chemokines. A review of the literature relating to localized heat activation of HSP promoters and HSP genes in the skin revealed that a multitude of different technologies has been explored in small animal models. In contrast, we uncovered few publications that examine HSP promoter activation in human skin. None of these publications has a therapeutic focus. We present herein two, clinically relevant, developments of heating technologies that effectively activate HSP promoters in targeted regions of human skin. The first development advances a system that is capable of reliably activating HSP promoters in human scalp, in particular in hair follicles. The second development outlines a simple, robust, and inexpensive methodology for locally activating HSP promoters in small, defined skin areas.

项与 HSF Pharmaceuticals SA 相关的新闻（医药）

2023-09-05

·PRNewswire

IEHP welcomes Healthcare Scholarship Fund recipients

RANCHO CUCAMONGA, Calif., Sept. 5, 2023 /PRNewswire/ -- When Mina Botros immigrated to the U.S. from Egypt at age 10, he became an Inland Empire Health Plan (IEHP) member. Now the 25-year-old Riverside resident is preparing to give back to the community he loves by becoming a doctor in the very place he calls home – the Inland Empire. Continue Reading Inland Empire Health Plan (IEHP) welcomed a new crop of Healthcare Scholarship Fund recipients to its fold during a special luncheon held at the not-for-profit health organization’s Rancho Cucamonga campus on Aug. 19. Scholars selected are currently studying medicine at three I.E.-based schools, with scholarship funds covering education-related expenses like tuition and books. 2023 Health Scholarship Fund recipients pose outside of Inland Empire Healthcare Plan (IEHP) headquarters on Aug. 19. Jarrod McNaughton, IEHP’s chief executive officer, delivers words of encouragement to this year’s Healthcare Scholarship Fund recipients during a welcome luncheon on Aug. 19. And in a full-circle moment, Botros once again has the heart of IEHP watching over him — this time in the form of a scholarship through the not-for-profit health organization's Healthcare Scholarship Fund. Known as HSF, the fund addresses two critical needs: providing financial support to physicians-in-training and closing the gap on the shortage of health care providers in the region. "[IEHP] was a big source of support for me to seek health care and everything I needed to start a new life here," recalled Botros, a second-year med student at Loma Linda University. "I got a lot of support out of IEHP, but I know there's a lot of people who didn't have that same support. And later on, I saw some family members and friends falling through the gaps and suffering from it; that's when my passion toward serving the Inland Empire community through health care was solidified." IEHP launched its HSF in 2020 in partnership with three local medical schools – Loma Linda University School of Medicine, University of California, Riverside, and California University of Science and Medicine in Colton. Since its inception, HSF has invested millions of dollars in the future of health care through full-ride scholarships intended to help offset costs associated with attending medical school. Along with Botros, this year's awardees join more than 100 scholarship recipients already in their respective career field studies. To welcome the 2023 Scholars to the HSF family, IEHP hosted a special luncheon for the students and their supporters on Aug. 19 at the company's headquarters in Rancho Cucamonga. Each scholar received messages of encouragement and tips of the trade from IEHP leaders, including IEHP Chief Executive Officer Jarrod McNaughton. "The Inland Empire is actually at the bottom of the list when it comes to the provider-to-population ratios in the state of California," McNaughton explained. "And so, the goal with this program is to have 50 full-ride medical school scholarships per year at the three medical schools in an attempt to go upstream and make sure you are well taken care of in the process … and you can really focus on [becoming] an incredible provider." The HSF program is just one way IEHP is working to address the critical need of health care within the areas it serves throughout San Bernardino and Riverside counties. The organization launched a Network Expansion Fund (NEF) Program – with a 73 percent retention rate – which serves as a subsidy to offset costs associated with hiring physicians. All NEF recipients must commit to three years of practicing within the IEHP network and with no restrictions. Since its launch, NEF has supported more than 450 physicians and advanced practitioners. To be considered as an HSF Scholar, med students must meet certain criteria based on their institution's respective eligibility requirements, and all must agree to practice in the region for five years with a contracted IEHP provider. In the meantime, IEHP will support HSF recipients throughout their academic journey by providing a helping hand whenever the need arises. "You'll be hearing a lot from us," McNaughton explained. "This is not a 'one-time wonder.' We really want to be engaged and support you through your journey." About IEHP With a mission to heal and inspire the human spirit, Inland Empire Health Plan (IEHP) is one of the top 10 largest Medicaid health plans, the largest not-for-profit Medicare-Medicaid plan in the country and for the third year in a row, certified as A Great Place To Work®. In its 27th year, IEHP supports nearly 1.7 million Riverside and San Bernardino County residents enrolled in Medicaid or IEHP DualChoice (those with both Medi-Cal and Medicare). Today, IEHP has a growing network of 7,000 providers and 3,000 team members who are fully committed to the vision: We will not rest until our communities enjoy optimal care and vibrant health. To learn more, visit iehp.org. SOURCE Inland Empire Health Plan (IEHP)

2023-06-16

·PRNewswire

Global Natural Source Vitamin E (Tocopherols and Tocotrienols) Market: Demand for Natural Vitamin E is Projected to Reach About 20K Metric Tons by 2028

DUBLIN, June 16, 2023 /PRNewswire/ -- The "Natural Source Vitamin E (Tocopherols and Tocotrienols) - A Global Market Overview" report has been added to ResearchAndMarkets.com's offering. Global demand for Natural Source Vitamin E reached US$1.1 billion in 2022, registering a YOY growth of 17% attributed to huge price increase in Tocopherols. Dietary Supplements sector is the largest consumer of Natural Vitamin E worldwide and any upturns and downturns in the demand from Dietary Supplements will directly reflect in the overall Natural Vitamin E market. Amid the pandemic induced upturn in the demand for supplements and fortified foods & beverages, the global Natural Vitamin E consumption has significantly increased during 2020-2021 period. Demand growth for supplements and fortified foods slowed down likewise significantly in 2022 as the threat by the pandemic continued to wane and the global economic conditions weakened. Rising energy costs, supply chain disruptions and tight supply of vegetable oil distillates has prompted Tocopherols producers to increase prices during the 2021-2022 period. As evident from the industry, vitamin E prices are expected to remain stable at 2022 levels during the forecast period (2022-2028) as the global supply chain conditions are improved and energy costs are coming down. In light of high inflation and rising Tocopherols prices, consumers are likely to become increasingly price sensitive heading into the forecast period, and the global volume consumption of Natural Vitamin E is projected to progress at a moderate CAGR of 3.6% between 2022 and 2025. As economic conditions are expected to back to normal after 2025, the global demand for Natural Vitamin E is projected to reach about 20K metric tons by 2028. Research Findings & Coverage Global Natural Source Vitamin E market is analyzed in this report with respect to key product types and major end-use sectors The study exclusively analyzes the market size of each product type and end-use sectors of Vitamin E by a major geographic region/country The market for Natural Vitamin E Tocopherols and Natural Vitamin E Tocotrienols is analyzed by end-use applications individually for all major regions/countries Analysis of Market Drivers, Restraints and Opportunities In-depth analysis is covered for global Natural Vitamin E market with respect to rising prices and inflation while the study also takes the recent pandemic impact in to consideration Production capacity shares of all major Tocopherols and Tocotrienols producers are analyzed Key business trends focusing on product innovations/developments, M&As, JVs and other recent industry developments Major companies profiled - 43 The industry guide includes the contact details for 223 companies Product Outline The report analyzes the market for the following key product types of Natural Vitamin E: Tocopherols Tocotrienols End-Use sectors of Natural Vitamin E analyzed comprise the following: Animal Nutrition/Feed Dietary Supplements Food and Beverages Cosmetics & Personal Care Others (include pharmaceuticals, medical nutrition, and infant nutrition) Analysis Period, Units and Growth Rates The report reviews, analyzes and projects the global Natural Vitamin E market for the period 2019-2028 in terms of volumes in Metric Tons and market value in US$ and the compound annual growth rates (CAGRs) projected from 2022 through 2028 with a special focus on y-o-y growth analysis for 2021-2022 Geographic Coverage North America (The United States, Canada and Mexico) Europe (Germany, France, Italy, Spain, The Netherlands, The United Kingdom and Rest of World) Asia-Pacific (China, India, Japan and Rest of Asia-Pacific) South America (Brazil, Argentina and Rest of South America) Rest of World Key Topics Covered: PART A: GLOBAL MARKET PERSPECTIVE 1. INTRODUCTION 1.1 Market Trends and Outlook 1.2 Overall Vitamin E Market At-a-Glance 1.3 Product Outline 1.3.1 What is Vitamin E? 1.3.2 Forms of Vitamin E 1.3.2.1 Synthetic Vitamin E 1.3.2.2 Natural Source Vitamin E 1.3.2.2.1 Tocopherols 1.3.2.2.2 Tocotrienols 1.3.2.2.3 Vitamin E TPGS (d-Alpha Tocopheryl Polyethylene Glycol 1000 Succinate) 1.3.3 Manufacturing Processes of Vitamin E 1.3.3.1 Synthetic Vitamin E 1.3.3.2 Natural Source Vitamin E 1.3.3.2.1 Tocopherols 1.3.3.2.2 Tocotrienols 1.3.4 Sources of Vitamin E 1.3.4.1 Food Sources 1.3.4.2 Dietary Supplements 1.3.5 Vitamin E Health Claims 1.3.5.1 Coronary Heart Disease 1.3.5.2 Cancer 1.3.5.3 Disorders of the Eyes 1.3.5.4 Cognitive Decline 1.3.5.5 Other Health Claims 1.3.6 End-Use Applications of Vitamin E 1.3.6.1 Animal Nutrition 1.3.6.2 Human Nutritional/Dietary Supplements 1.3.6.3 Functional Food and Beverages 1.3.6.4 Cosmetics 1.3.6.5 Other Applications 2. REGULATIONS FOR DIETARY SUPPLEMENTS AND INGREDIENTS 2.1 Ministry of Health Malaysia Approves Two Health Claims for Palm Tocotrienols 2.2 Regulations for Dietary Supplements and Ingredients as per the US Food and Drug Administration (FDA) 2.2.1 How the Safety of Dietary Supplements is Ensured 2.2.2 Registration of Food Facilities 2.2.3 Notification Process for New Dietary Ingredients 2.3 FDA Changes Nutrition Facts Label on Food Packaging 2.3.1 FDA Guidance for Industry on Converting Units of Measure for Vitamin E 2.4 European Union: Traceability and Labeling of GMOs 3. INDUSTRY LANDSCAPE 3.1 Global Vitamin E Production Capacities 3.1.1 Global Natural Vitamin E Tocopherols Capacity 3.1.2 Global Natural Vitamin E Tocotrienols Capacity 3.2 Natural Vitamin E Tocopherols Manufacturers Advanced Organic Materials S.A. (Argentina) Archer Daniels Midland Company (United States) BTSA Biotecnologias Aplicadas Sl (Spain) COFCO Tech Bioengineering (Tianjin) Co., Ltd. (China) DSM Nutritional Products (Royal DSM NV) (Netherlands) Cargill, Inc (United States) ECA Healthcare Inc. (China) Fairchem Organics Limited (India) Fenchem Biotek Ltd. (China) Fujian Fuerjin Biotechnology Co., Ltd. (China) Fujian Glanny Bio-Engineering Co., Ltd. (China) Jiangsu Conat Biological Products Co., Ltd. (China) Jiangsu Xixin Vitamin Co., Ltd. (China) Jiangsu Yuehong Bio-Tec Co., Ltd. (China) Jiangxi Aturex Co Ltd (China) J-Oil Mills, Inc. (Japan) Kensing, LLC. (United States) Vitae Naturals (Spain) Matrix Life Science Pvt. Ltd. (India) Mitsubishi-Chemical Foods Corporation (Japan) Tama Biochemical Co., Ltd. (Japan) Ningbo Dahongying Bio-Engineering Co., Ltd. (China) Riken Vitamin Co., Ltd. (Japan) Shandong New Element Biotechnology Co., Ltd. (China) Vitae Naturals (Vitae Caps, S.A.) (Spain) Wilmar Spring Fruit Nutrition Products (Jiangsu) Co., Ltd. (China) Xi'an Healthful Biotechnology Co Ltd (HSF) (China) Yichun Dahaigui Life Science Co., Ltd. (China) Zhejiang Medicine Co., Ltd. (China) Zhejiang Worldbestve Biotechnology Co., Ltd. (China) 3.3 Natural Vitamin E Tocotrienols Manufacturers American River Nutrition, Inc. (United States) Beijing Gingko Group (China) ExcelVite Sdn. Bhd. (Malaysia) KLK Oleo (Davos Life Science) (Singapore) Musim Mas Group (Singapore) Oryza Oil & Fat Chemical Co., Ltd. (Japan) Pwani Oil Products Limited (Kenya) ORAH Nutrichem Exim Pvt. Ltd. (India) Phytogaia Sdn. Bhd. (Malaysia) Sime Darby Oils Nutrition (Malaysia) SOP Nutraceuticals Sdn. Bhd. (Malaysia) Supervitamins Sdn. Bhd. (Malaysia) Vance Group Ltd. (Singapore) 4. KEY BUSINESS TRENDS Kensing Acquires Spain-based Natural Vitamin E Producer Vitae Naturals ORAH Nutrichem Introduces ORAH VIT E Tocotrienol based Natural Antioxidant Kensing Inks Distribution Deal with Azelis in the EMEA Region One Rock Capital Partners Acquires BASF's Kankakee, Illinois Natural Vitamin E Plant Antares Introduces Pharmaceutical and Food Grade Non-GMO Sunflower TPGS 5. GLOBAL MARKET OVERVIEW 5.1 Global Natural Vitamin E Market Overview by End-Use Application 5.2 Global Natural Vitamin E Market Overview by Type 5.2.1 Natural Vitamin E - Tocopherols 5.2.1.1 Global Natural Vitamin E Tocopherols Market Overview by End-Use Application 5.2.2 Natural Vitamin E - Tocotrienols 5.2.2.1 Global Natural Vitamin E Tocotrienols Market Overview by End-Use Application PART B: REGIONAL MARKET PERSPECTIVE Natural Vitamin E Market Overview by Geographic Region Global Natural Vitamin E Tocopherols Market Overview by Geographic Region Global Natural Vitamin E Tocotrienols Market Overview by Geographic Region REGIONAL MARKET OVERVIEW 6. NORTH AMERICA 7. EUROPE 8. ASIA-PACIFIC 9. SOUTH AMERICA 10. REST OF WORLD PART C: GUIDE TO THE INDUSTRY 1. Major Manufacturers and Suppliers of Vitamin E Manufacturers of Natural Vitamin E Tocopherols Manufacturers of Natural Vitamin E Tocotrienols Vitamins and Other Ingredients Distributors 2. Major Companies in the End-use Application Industries for Vitamin E Nutritional Supplements Companies Direct Selling Companies - Supplements and Personal Care Contract Manufacturers - Supplements Animal Feed/Nutrition Companies Vitamins and Other Ingredients Distributors and Formulators PART D: ANNEXURE 1. RESEARCH METHODOLOGY 2. FEEDBACK For more information about this report visit About ResearchAndMarkets.com ResearchAndMarkets.com is the world's leading source for international market research reports and market data. We provide you with the latest data on international and regional markets, key industries, the top companies, new products and the latest trends. Media Contact: Research and Markets Laura Wood, Senior Manager [email protected] For E.S.T Office Hours Call +1-917-300-0470 For U.S./CAN Toll Free Call +1-800-526-8630 For GMT Office Hours Call +353-1-416-8900 U.S. Fax: 646-607-1907 Fax (outside U.S.): +353-1-481-1716 Logo: SOURCE Research and Markets

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