University of Catania

Polyphenols, abundant in fruits, vegetables, tea, and coffee, offer potential health benefits. However, owing to low bioavailability, the mechanisms underlying their beneficial effects remain unknown. In a recent study, researchers have explored the interaction between polyphenols and human sensory receptors. Their findings elucidate how polyphenols influence brain function and metabolic pathways by interacting with gut receptors, explaining their role in well-being and nutrition innovation. Polyphenols are powerful plant metabolites known for their antioxidant properties, offering potential health benefits and protection against various diseases. With over 8,000 identified varieties, these substances are found in plentiful amounts in various fruits, vegetables, tea, and coffee. Besides adding color and flavor to foods, polyphenols play a crucial role in promoting health and overall well-being. Despite their bitter and astringent taste, recent studies indicate that they may hold the key to a range of health benefits, including the prevention of cardiovascular diseases, neurodegenerative conditions, and age-related sensory decline. However, there are significant gaps in understanding how exactly they exert these beneficial effects, particularly in terms of their interactions with the body. To fill this knowledge gap, Professor Naomi Osakabe along with Dr. Yasuyuki Fujii from Shibaura Institute of Technology, and Professor Vittorio Calabrese from the University of Catania, Italy explored the interaction between polyphenols and human health, and its consequent impact. The findings of their study were published in Volume 14, Issue 2 of Biomolecules on 17th February, 2024. Sharing the inspiration behind their work Prof. Osakabe remarks, "Although many researchers have conducted polyphenol research for more than 30 years, a major challenge has been to elucidate the mechanisms behind their beneficial health effects." This review attempts to understand the ways in which polyphenols interact with sensory receptors in the gastrointestinal tract, ultimately influencing metabolic pathways and promoting overall well-being. Epidemiological evidences have long established the protective effects of polyphenols against various chronic conditions such as cardiovascular diseases, metabolic disorders, neurodegenerative diseases, and age-related degeneration of sensory organs. The major challenge in decoding the underlying mechanism of action is their unavailability in blood and/or organs. Polyphenols are usually broken down in the lower gut by intestinal bacteria and excreted in feces. Recent studies have reported that ingested dietary polyphenols can alter the composition of the gut microflora, altering the composition of secondary metabolites in the colon. It is hypothesized that these altered metabolites may be absorbed and affect the metabolic and cognitive functions. However, the type and amount of polyphenol varies greatly with diet and individuals making it quite difficult to establish a causal correlation. Sensory receptors are specialized cells located close to nerve endings and are widely distributed in specialized organs such as eyes, ears, and even the gut. In recent years, sensory nutrition, a new field of study examining the cross-talk between ingested food or beverages, the brain, and its impact on human behavior, has garnered significant attention. Some reports have suggested that food signals contribute to homeostasis via gut-based sensory receptors. Delving deeper to unearth the association between polyphenols and the gut, researchers in this study revealed that polyphenols, which are inherently bitter in taste, interact with the bitter taste receptor, the taste receptor 2 (T2R) receptors. Furthermore, some studies found that until polyphenols are excreted, they stay in contact with I-, K-, and L- cells of the intestine expressing T2Rs, or with gastrointestinal sensory nerves and epithelial cells that express TRP channels for an extended time. Astringency of polyphenols was suggested to be a somatosensory perception (a sensation which can occur anywhere in the body) and was correlated with improved blood pressure and risk factors for heart diseases. Polyphenols caused a marked increase in blood flow-dependent vasorelaxation (FMD) levels at moderate doses, known as the hormetic effect. Researchers have found that astringent polyphenols interact with transient receptor potential (TRP) channels. However, further investigation is needed to clearly understand this interaction. These findings strongly suggested that polyphenols exert their beneficial effects via sensory receptors of the gastrointestinal tract. The astringent and bitter properties of polyphenols offer various therapeutic properties. An experimental animal study demonstrated that repeated intake of stringent polyphenols reduced FMD response significantly along with blood pressure. Another study reported that consumption of bitter polyphenols increased gastrointestinal hormone secretion, thereby regulating blood glucose levels and glucose tolerance. Astringent polyphenols have been observed to regulate the hypothalamic-pituitary-adrenal (HPA) axis activation, thereby improving mood and memory function. Bitter and astringent perception of polyphenols have also been attributed for their anti-obesity effects. The integration of polyphenol-rich ingredients in functional beverages and snacks, could therefore revolutionize the way we approach nutrition and disease prevention. Elaborating on the long-term impact of their work, a hopeful Prof. Osakabe explains, "Our study is the first to identify that sensory stimuli in food can promote homeostasis and paves the way for the development of novel food products aimed at promoting human health." Overall, by comprehensively looking at the underlying mechanisms responsible for the beneficial effects of polyphenols, this review represents a significant step forward in our understanding of the health effects of polyphenols and could pave the way towards innovative dietary interventions for well-being.

LEWISVILLE, Texas--( BUSINESS WIRE )-- Orthofix Medical Inc . (NASDAQ: OFIX), a leading global spine and orthopedics company, today announced that effective immediately, Massimo Calafiore has assumed the role of President and Chief Executive Officer (CEO) and as a member of the Orthofix Board of Directors. In conjunction with Mr. Calafiore stepping into his role as CEO, the Company has announced the appointment of Julie Andrews as Chief Financial Officer. Ms. Andrews previously served as CFO for Smart Wires Technology, where she led all finance, tax, treasury, accounting, information technology, and investor relations functions. Prior to that role, Ms. Andrews served as the Senior Vice President, Global Finance for Wright Medical Group, a global medical device company focused on extremities and biologics that was acquired by Stryker in 2020, and before that, she was the Vice President of Finance for the Spine and Biologics division of Medtronic Inc. “I am thrilled to announce that Massimo has officially started in his role as President and CEO and am equally excited to welcome Julie to Orthofix as incoming CFO,” said Catherine Burzik, Chair of the Board of Directors and former Interim CEO of Orthofix. “Our search for these critical management roles was executed quickly and thoroughly, with many highly qualified candidates expressing interest in leading Orthofix. We are confident we have chosen two visionary executives who will bring meaningful perspectives and expertise to the Company and that their leadership will serve us well in the years ahead.” Mr. Calafiore commented, “I am honored to officially begin this role at this important time for the Company, and I am excited to welcome Julie to the team next week. I look forward to working with the more than 1,600 employees who dedicate themselves to furthering our mission to deliver meaningful and life-improving technologies for our surgeon customers and their patients.” About Massimo Calafiore Mr. Calafiore joined LimaCorporate S.p.A., a global orthopedics company in September 2022, where he served as CEO until the January 3, 2024, acquisition of LimaCorporate by Enovis Corporation (NYSE: ENOV). Prior to this he served as Executive Vice President and Chief Commercial Officer of NuVasive, Inc. During his tenure at NuVasive, Mr. Calafiore served as President of NuVasive Specialized Orthopedics (formerly Ellipse Technologies). Earlier in his career, Mr. Calafiore worked for Waldemar Link GmbH & Co. KG and served in various leadership roles across multiple business segments, including orthopedics, lower extremities, and spine. He received his M.Sc. in Mechanical Engineering from the University of Catania and an MBA from New York University. About Julie Andrews Ms. Andrews joined Smart Wires Technology, a global transmission grid technology company focused on enabling the transition to renewable energy, as CFO in 2021. From 2012 to 2020, she served as Senior Vice President, Global Finance and Vice President, Global FP&A, and Chief Accounting Officer at Wright Medical Group, where Ms. Andrews led a 170-person finance team. Prior to this, Ms. Andrews spent many years in roles of increasing responsibility at Medtronic Inc., including as Vice President of Finance for the Spine and Biologics division, where she provided oversight of all FP&A and accounting functions. Early in her career, Ms. Andrews served as a Senior Financial Analyst for Thomas & Betts and as an auditor for Thomas Havey, LLC. Currently, she serves on the board of RxSight, Inc., an ophthalmic medical device company. Ms. Andrews received a Bachelor of Science in Accounting from Indiana University. She also participated in advanced leader and director development programs at both Medtronic and Wharton School of Business. About Orthofix Orthofix is a leading global spine and orthopedics company with a comprehensive portfolio of biologics, innovative spinal hardware, bone growth therapies, specialized orthopedic solutions, and a leading surgical navigation system. Its products are distributed in approximately 68 countries worldwide. The Company is headquartered in Lewisville, Texas and has primary offices in Carlsbad, CA, with a focus on spine and biologics product innovation and surgeon education, and Verona, Italy, with an emphasis on product innovation, production, and medical education for orthopedics. The combined Company’s global R&D, commercial and manufacturing footprint also includes facilities and offices in Irvine, CA, Toronto, Canada, Sunnyvale, CA, Wayne, PA, Olive Branch, MS, Maidenhead, UK, Munich, Germany, Paris, France and Sao Paulo, Brazil. Forward-Looking Statements This news release may include forward-looking statements within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended, and Section 27A of the Securities Act of 1933, as amended. In some cases, you can identify forward-looking statements by terminology such as “may,” “will,” “should,” “expects,” “plans,” “anticipates,” “believes,” “estimates,” “projects,” “intends,” “predicts,” “potential,” “continue” or other comparable terminology. Orthofix cautions you that statements included in this news release that are not a description of historical facts are forward-looking statements that are based on the Company’s current expectations and assumptions. Each forward-looking statement contained in this news release is subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statement. Applicable risks and uncertainties include, among others: the ability of newly launched products to perform as designed and intended and to meet the needs of surgeons and patients, including as a result of the lack of robust clinical validation; and the risks identified under the heading “Risk Factors” in Orthofix Medical Inc.’s Annual Report on Form 10-K for the fiscal year ended December 31, 2022, which was filed with the Securities and Exchange Commission (SEC) on March 6, 2023. The Company’s public filings with the Securities and Exchange Commission are available at www.sec.gov . You are cautioned not to place undue reliance on forward-looking statements, which speak only as of the date when made. Orthofix does not intend to revise or update any forward-looking statement set forth in this news release to reflect events or circumstances arising after the date hereof, except as may be required by law.

Value-Building Medical Device Executive with 20-Year Record of Driving Market-Leading Growth Across Orthopedics and Spine Businesses Global Leader with Extensive M&A Integration Expertise and Commercial and Operating Experience Across Key Orthofix Geographies LEWISVILLE, Texas--(BUSINESS WIRE)-- Orthofix Medical Inc. (NASDAQ:OFIX), a leading global spine and orthopedics company, announced today that Massimo Calafiore has been named incoming President and Chief Executive Officer. Mr. Calafiore is currently Chief Executive Officer of LimaCorporate S.p.A., a global orthopedics company, and his appointment to Orthofix is expected to be effective in early 2024, following the completion of LimaCorporate’s previously announced acquisition by Enovis Corporation (NYSE: ENOV). At that time, Mr. Calafiore is also expected to join Orthofix’s Board of Directors. This press release features multimedia. View the full release here: Massimo Calafiore, Incoming President and CEO, Orthofix Medical Inc. (Photo: Business Wire) “The Board of Directors unanimously determined that Massimo is the right choice to lead Orthofix given his exceptional track record of delivering value creation and his extensive knowledge of the medical device industry, specifically within orthopedics and spine,” said Catherine Burzik, Chair of the Board of Directors and Interim CEO of Orthofix. “Throughout his career, Massimo has demonstrated his ability to unlock value opportunities for multi-segmented, global businesses. He has successfully driven sales and commercial operations to achieve both industry leading profitability and growth. Importantly, he has proven experience integrating companies and building high performing teams.” “Having worked in orthopedics and spine throughout my entire career, I know Orthofix well and have long admired the Company and its talented team,” said Mr. Calafiore. “I was attracted to Orthofix given the many growth opportunities created by its unique, broad-based portfolio and high-quality distributor relationships. I am also impressed with the innovative solutions Orthofix has developed to meet the needs of surgeons and the patients it serves. At this pivotal time for the Company, I look forward to working with the Board and leadership team to capture Orthofix’s significant profitable growth potential and drive enhanced shareholder value.” Mr. Calafiore is an accomplished global business leader with an excellent track record across multiple companies in the orthopedics and spine industry. Throughout his career he has demonstrated a commitment to operating excellence, ethical integrity and DE&I values. He has been CEO of LimaCorporate since September 2022. During this time, Mr. Calafiore strengthened and reshaped the company’s strategy and culture priorities, with an emphasis on fostering, mentoring and retaining talent. His leadership resulted in consecutive quarter-over-quarter above-market growth; best-in-class EBITDA margins; and substantial improvement in employee engagement and retention. On September 25, 2023, LimaCorporate announced its sale to Enovis Corporation for €800 million. Prior to LimaCorporate, he served as Executive Vice President and Chief Commercial Officer of NuVasive, Inc. and delivered consecutive quarter-over-quarter above-market growth in all core geographies, including the U.S., APAC, EMEA and Japan, and successfully launched multiple products globally, which became foundational to NuVasive’s portfolio offering. At the beginning of his tenure at NuVasive, Mr. Calafiore served as President of NuVasive Specialized Orthopedics (formerly Ellipse Technologies). In this role, he helped to further integrate the Ellipse business with NuVasive, achieving multiple quarters of accelerated revenue growth with above-market operation margin expansion. NuVasive Specialized Orthopedics is today an important player in complex trauma and limb reconstruction for adults and children, a market segment where Orthofix is also a recognized leader. Earlier in his career, Mr. Calafiore worked for Waldemar Link GmbH & Co. KG and served in various leadership roles across multiple business segments, including orthopedics, lower extremities and spine. He oversaw the sales of the STAR Ankle to Small Bone Innovations and the PCM Cervical disc to NuVasive. He holds an M.Sc. in Mechanical Engineering from the University of Catania and an MBA from New York University. The Company also announced that Ms. Burzik has notified the Board that she has elected to not stand for reelection to the Board at the 2024 Annual Meeting. Ms. Burzik said, “It is an honor to serve as Interim CEO and work closely with Orthofix’s amazing employees. The organization is on solid footing, and I will be delighted to turn the Company over to Massimo’s very capable hands and plan to work closely with him in the following months to ensure a seamless transition.” The Board retained Heidrick & Struggles, a leading global executive search firm, to assist in its search process. About Orthofix Orthofix is a leading global spine and orthopedics company with a comprehensive portfolio of biologics, innovative spinal hardware, bone growth therapies, specialized orthopedic solutions, and a leading surgical navigation system. Its products are distributed in approximately 68 countries worldwide. The Company is headquartered in Lewisville, Texas and has primary offices in Carlsbad, CA, with a focus on spine and biologics product innovation and surgeon education, and Verona, Italy, with an emphasis on product innovation, production, and medical education for orthopedics. The combined Company’s global R&D, commercial and manufacturing footprint also includes facilities and offices in Irvine, CA, Toronto, Canada, Sunnyvale, CA, Wayne, PA, Olive Branch, MS, Maidenhead, UK, Munich, Germany, Paris, France and Sao Paulo, Brazil. Forward-Looking Statements This news release may include forward-looking statements within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended, and Section 27A of the Securities Act of 1933, as amended. In some cases, you can identify forward-looking statements by terminology such as “may,” “will,” “should,” “expects,” “plans,” “anticipates,” “believes,” “estimates,” “projects,” “intends,” “predicts,” “potential,” “continue” or other comparable terminology. Orthofix cautions you that statements included in this news release that are not a description of historical facts are forward-looking statements that are based on the Company’s current expectations and assumptions. Each forward-looking statement contained in this news release is subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statement. Applicable risks and uncertainties include, among others: the ability of newly launched products to perform as designed and intended and to meet the needs of surgeons and patients, including as a result of the lack of robust clinical validation; and the risks identified under the heading “Risk Factors” in Orthofix Medical Inc.’s Annual Report on Form 10-K for the fiscal year ended December 31, 2022, which was filed with the Securities and Exchange Commission (SEC) on March 6, 2023. The Company’s public filings with the Securities and Exchange Commission are available at . You are cautioned not to place undue reliance on forward-looking statements, which speak only as of the date when made. Orthofix does not intend to revise or update any forward-looking statement set forth in this news release to reflect events or circumstances arising after the date hereof, except as may be required by law.