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In Honor of Nobel Laureate Dr. Aaron Ciechanover

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SIPS 2025 takes place from November 17-20, 2025 at the Dusit Thani Mactan Resort in Cebu, Philippines

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More than 400 abstracts submitted from over 50 countries
Abstracts Still Accepted for a Limited Time



Featuring many Nobel Laureates and other Distinguished Guests

ADVANCED PROGRAM

Orals | Summit Plenaries | Round Tables | Posters | Authors Index


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Oral Presentations


08:00 SUMMIT PLENARY - Dusit Ballroom
12:00 LUNCH - Tradewinds Café

SESSION:
OxidativeTuePM1-R2
Inufusa International Symposium (5th Intl. Symp. on Oxidative Stress for Sustainable Development of Human Beings)
Tue. 18 Nov. 2025 / Room: Dusit 2
Session Chairs: Fuhua Yang; Koji Fukui; Student Monitors: TBA

14:00: [OxidativeTuePM104] OS Keynote
OXIDATIVE STRESS AND BRAIN INFLAMMATION INDUCES WIDE AREA DISEASES
Haruhiko Inufusa1; Fuhua Yang1; Kentaro Omoya1; Yoshiaki Harakawa1; Shigeru Hirano2; Yoichiro Sugiyama3; Yuki Sato3; Koji Fukui4
1Gifu University, Gifu, Japan; 2Kyoto Prefectural University of Medicine, Kyoto, Japan; 3Saga University, Saga, Japan; 4Shibaura Institute of Technology, Saitama, Japan
Paper ID: 256 [Abstract]

In human brain tissue, oxidative stress (OS) induces various inflammatory cytokines, leading to inflammation. This inflammation causes diverse damage not only in the affected brain area but also in surrounding brain tissue.Long-term damage to brain tissue can impair the brain's autophagy function, reducing its ability to clear waste, leading to the accumulation of waste products such as amyloid beta and tau proteins, and creating a vicious cycle of further oxidative stress. Dementia is a representative disease of this process, and the development of pharmaceuticals has been challenging due to the diverse nature of the target waste products.Twendee X (TwX) is a supplement composed of eight vitamins, amino acids, CoQ10, and other ingredients, with clinical trial-confirmed preventive effects against dementia in humans. Other diseases closely associated with OS in brain neurons include hypertension, atherosclerosis, hearing loss/tinnitus, ALS, Parkinson's disease, post-stroke sequelae, chronic fatigue syndrome, depression, and sleep apnea syndrome.TwX is an antioxidant formulation that has been shown to be safe for use in both clinical and basic research, and it is expanding the field of antioxidant therapy, which has previously been challenging. The importance of antioxidant therapy is beginning to be recognized in the expansion of treatment targets for inflammatory diseases caused by oxidative stress in the brain and in basic research fields.



14:20 POSTERS - Ballroom Foyer

SESSION:
OxidativeTuePM3-R2
Inufusa International Symposium (5th Intl. Symp. on Oxidative Stress for Sustainable Development of Human Beings)
Tue. 18 Nov. 2025 / Room: Dusit 2
Session Chairs: Davis Joseph; Haruhiko Inufusa; Student Monitors: TBA

16:05: [OxidativeTuePM309] OS Plenary
DISEASE PREVENTION: THE RELATIONSHIP BETWEEN LIFESTYLE HABITS AND OXIDATIVE STRESS
Fuhua Yang1; Yoshiaki Harakawa1; Kentaro Omoya1; Haruhiko Inufusa1
1Gifu University, Gifu, Japan
Paper ID: 131 [Abstract]

The COVID-19 pandemic has led to an increase in the number of people suffering from various diseases, with patients becoming younger. In addition, rising medical costs and drug shortages are exacerbating the situation, such as becoming impossible to adequately treat diseases that should normally be treatable, raising concerns about future health risks. As the current state of medical care is likely to persist, disease prevention will become increasingly important in the future. Inflammation is at the root of all diseases, including aging, common lifestyle-related diseases, designated intractable diseases, and even unknown diseases. Oxidative stress is closely associated with inflammation. Prolonged exposure to inflammation and oxidative stress can accelerate the onset of diseases, making it crucial to suppress oxidative stress. We have been investigating the effects of Twendee X and Twendee Mtcontrol, antioxidant combinations, on various diseases. While it is well known that oxidative stress increases with age, lifestyle factors are also closely related. These factors can be broadly categorized into preferences, diet, exercise, and sleep. We summarized the results of previous studies on how these factors increase oxidative stress and how they affect the body's homeostasis. Based on these findings, we discuss the importance of improving lifestyle through antioxidant supplements.

References:
[1] Fukka You, Carole Nicco, Yoshiaki Harakawa, Toshikazu Yoshikawa, Haruhiko Inufusa. The Potential of Twendee X® as a Safe Antioxidant Treatment for Systemic Sclerosis. Int J Mol Sci. March 2024;25(5):3064.
[2] Ranganathan, P.; Rao, K.A.; Sudan, J.J.; Balasundaram. S. Cadmium effects on sperm morphology and semenogelin with relates to increased ROS in infertile smokers: An in vitro and in silico approach. 2018, 18, 189-197. doi: 10.1016/j.repbio.2018.04.003
[3] Kucheria, K.; Saxena, R.; Mohan, D. Semen analysis in alcohol dependence syndrome. Andrologia. 1985, 17, 558-563. doi:10.1111/j.1439-0272.1985.tb01714.xYou F, Harakawa Y, Yoshikawa T, Inufusa H. Controlling Gut Microbiota by Twendee X® May Contribute to Dementia Prevention. Int J Mol Sci. 2023 Nov 23;24(23):16642. doi: 10.3390/ijms242316642.
[4] Fukui, K.; You, F.; Kato, Y.; Kimura, M.; Harakawa, Y.; Yoshikawa, T.; Inufusa, H. Twendee X, a mixed antioxidant supplement, improves cognitive function, coordination, and neurotrophic factor expression in long-term vitamin E-deficient mice. J Clin Biochem Nutr. 2023, 72, 93-100. doi: 10.3164/jcbn.22-55.
[5] Vaccaro A, Dor YK, Rogulja D, et al. Sleep Loss Can Cause Death through Accumulation of Reactive Oxygen Species in the Gut. Cell. 2020 Jun 11;181(6):1307-1328.


17:05: [OxidativeTuePM312] OS Invited
ANTIOXIDANT SUPPLEMENTS AS A MEASURE AGAINST ELECTROMAGNETIC WAVES
Yoshiaki Harakawa1; Fuhua Yang1; Kentaro Omoya1; Haruhiko Inufusa1
1Gifu University, Gifu, Japan
Paper ID: 132 [Abstract]

Nowadays, our surroundings are filled with electrical devices that emit electromagnetic waves. The electromagnetic waves emitted by devices such as mobile phones, wireless earphones, high-voltage power lines, electric cookers and electric blankets have the same properties as radiation; they differ only in wavelength. Exposure to these waves causes water molecules in the body to ionize, producing hydrogen peroxide and increasing oxidative stress. Oxidative stress contributes to numerous diseases and adverse effects of electromagnetic waves have been reported, including infertility, leukaemia and cancer. As it is impractical to avoid electromagnetic wave-emitting devices entirely, it is necessary to take measures to counteract the oxidative stress they cause.
Twendee X (TwX) is an antioxidant supplement containing vitamins, amino acids and CoQ10. It has passed pharmaceutical-level safety tests and can be used safely by both children and adults. Previous studies have proven that TwX suppresses the increase in oxidative stress caused by radiation exposure. Here, we discuss the potential effectiveness of an antioxidant in countering electromagnetic wave-induced oxidative stress in everyday environments. It incorporates measurement results of electromagnetic waves from common electronic devices, such as mobile phones and wireless earbuds.

References:
[1] Sciorio R, Tramontano L, Esteves SC. Effects of mobile phone radiofrequency radiation on sperm quality. Zygote. 2022 Apr;30(2):159-168.
[2] Brabant C, Geerinck A, Beaudart C, Tirelli E, Geuzaine C, Bruyère O. Exposure to magnetic fields and childhood leukemia: a systematic review and meta-analysis of case-control and cohort studies. Rev Environ Health. 2022 Mar 15;38(2):229-253.
[3] Gupta S, Sharma RS, Singh R. Non-ionizing radiation as possible carcinogen. Int J Environ Health Res. 2022 Apr;32(4):916-940.
[4] You F, Harakawa Y, Yoshikawa T, Inufusa H. Why Does the Antioxidant Complex Twendee X® Prevent Dementia? Int J Mol Sci. 2023 Aug 21;24(16):13018.





08:00 SUMMIT PLENARY - Dusit Ballroom
12:00 LUNCH - Tradewinds Café

SESSION:
OxidativeWedPM1-R2
Inufusa International Symposium (5th Intl. Symp. on Oxidative Stress for Sustainable Development of Human Beings)
Wed. 19 Nov. 2025 / Room: Dusit 2
Session Chairs: Haruhiko Inufusa; Motoki Watanabe; Student Monitors: TBA

13:20: [OxidativeWedPM102] OS Plenary
THE EFFECTS OF OXIDATIVE STRESS IN ORTHOSTATIC DYSREGULATION
Kentaro Omoya1; Fuhua Yang1; Yoshiaki Harakawa1; Haruhiko Inufusa1
1Gifu University, Gifu, Japan
Paper ID: 152 [Abstract]

Orthostatic dysregulation (OD) is most common during adolescence, with approximately 5-10% of junior high and high school students in Japan believed to be affected. According to Japanese clinical guidelines, this condition is classified into four subtypes: “instantaneous orthostatic hypotension (INOH)”, “postural tachycardia syndrome (POTS)”, “vasovagal syncope (VVS)” and “delayed orthostatic hypotension (delayed OH)”. Additionally, it is noted that various factors, including idiopathic causes, nutritional deficiencies, developmental disorders, and mental health issues, may contribute to its onset.

On the other hand, cases of OD symptoms have been reported among adult patients with chronic fatigue syndrome (ME/CFS), and it has been clarified that increased oxidative stress is involved in some of these cases. Additionally, there are cases where symptom improvement has been observed through antioxidant therapy.

Based on a summary of previous studies and initial data obtained, this report examines the trends in the association between each subtype of pediatric OD and oxidative stress markers, and discusses the potential involvement of oxidative stress in pediatric OD and implications for future treatment strategies. 

References:
[1] Tanaka H, et al. Pediatr Int. 2009 51(1):169-79.
[2] Del Pozzi AT, et al. Am J Physiol Heart Circ Physiol. 2014 1;307(3):H397-404.
[3] Stewart JM, et al. Am J Physiol Heart Circ Physiol. 2011;301(3):H1033-42.


14:20 POSTERS - Ballroom Foyer

SESSION:
OxidativeWedPM3-R2
Inufusa International Symposium (5th Intl. Symp. on Oxidative Stress for Sustainable Development of Human Beings)
Wed. 19 Nov. 2025 / Room: Dusit 2
Session Chairs: Kentaro Omoya; Yoichiro Sugiyama; Student Monitors: TBA

17:05: [OxidativeWedPM312] OS Keynote
THE ROLE OF OXIDATIVE STRESS IN KAWASAKI DISEASE AND ITS CLINICAL SIGNIFICANCE
Kentaro Omoya1; Fuhua Yang1; Yoshiaki Harakawa1; Haruhiko Inufusa1
1Gifu University, Gifu, Japan
Paper ID: 155 [Abstract]

Kawasaki disease (KD) is an acute systemic vasculitis of unknown etiology that primarily affects infants and young children. In Japan, it represents the leading cause of acquired heart disease in children. The most serious complication is the development of coronary artery lesions (CAL), which are directly associated with long-term cardiovascular risk. Although immune dysregulation, genetic predisposition, and infectious triggers have been implicated in the pathogenesis of KD, increasing attention has been directed toward the involvement of oxidative stress (OS). 

During the acute phase of KD, OS caused by excessive production of reactive oxygen species (ROS) and impaired antioxidant defense mechanisms contributes to vascular inflammation through endothelial cell injury, enhanced cytokine production, and platelet dysfunction. High OS levels in the early phase have been associated with an increased risk of CAL, and OS biomarkers may serve as potential predictors of disease severity. Moreover, OS may persist into the subacute and chronic phases, even after the resolution of overt inflammation. This ongoing oxidative imbalance may impair vascular recovery and contribute to long-term vascular dysfunction, possibly accelerating the development of atherosclerosis. In recent years, the clinical application of OS-related biomarkers has emerged, offering new opportunities for mechanistic disease assessment and the development of personalized treatment strategies.

This presentation summarized current evidence regarding the role of OS in the pathophysiology of KD, and explores how OS-based evaluation and therapeutic approaches may enhance clinical care and prognosis in pediatric patients.

References:
[1] Tsuge M, et al. Roles of Oxidative Injury and Nitric Oxide System Derangements in Kawasaki Disease Pathogenesis: A Systematic Review. Int J Mol Sci. 2023 Oct 22;24(20):15450.
[2] Yang Li, et al. Expression of Oxidative Stress and Inflammatory Indicators for Coronary Artery Disease in Kawasaki Disease. Mediterr J Hematol Infect Dis. 2024 Jul 1;16(1):e2024052.
[3] Hara T, et al. The up-to-date pathophysiology of Kawasaki disease. Clin Transl Immunology. 2021 May 10;10(5):e1284.





08:00 SUMMIT PLENARY - Dusit Ballroom
12:00 LUNCH - Tradewinds Café

SESSION:
OxidativeThuPM1-R2
Inufusa International Symposium (5th Intl. Symp. on Oxidative Stress for Sustainable Development of Human Beings)
Thu. 20 Nov. 2025 / Room: Dusit 2
Session Chairs: Yuki Sato; Keiichiro Okano; Student Monitors: TBA

13:00: [OxidativeThuPM101] OS Plenary
OXIDATIVE STRESS AND HEAT SHOCK PROTEIN
Haruhiko Inufusa1; Fuhua Yang1; Yoshiaki Harakawa1; Shigeru Hirano2; Yoichiro Sugiyama3; Yuki Sato3; Koji Fukui4; Kentaro Omoya1
1Gifu University, Gifu, Japan; 2Kyoto Prefectural University of Medicine, Kyoto, Japan; 3Saga University, Saga, Japan; 4Shibaura Institute of Technology, Saitama, Japan
Paper ID: 254 [Abstract]

Research on Heat Shock Proteins (HSPs) is widely conducted, and their name suggests that they are proteins primarily responsive to heat stimuli. However, some HSPs respond to oxidative stress (OS) and inflammation.

HSP70, with a molecular weight of 70 kDa, is conserved in nearly all biological species and is the most well-characterized HSP in response to oxidative stress, with numerous reports available. HSP70 not only responds to OS but also has been reported to increase oxidative stress when inhibited. HSP90 is another important HSP, which is constantly expressed and maintains the structure of the NOX enzyme family that produces reactive oxygen species (ROS), thereby promoting ROS production.HSP90 inhibitors are being studied as anticancer agents. HPS27 is strongly induced by heat, OS, and drugs, and its levels significantly increase in cancer and OS responses. Since opportunities for OS to rise and inflammation to occur are more common in humans than prolonged exposure to saunas or hot baths, it is considered that OS triggers HSP responses in the human body. Following the development of Twendee X (TwX), safe antioxidant therapy for humans has become possible.TwX is a supplement composed of eight vitamins, amino acids, CoQ10, and other ingredients, and its efficacy has been confirmed in human and animal experiments for the following conditions:Dementia, cancer, hypertension, atherosclerosis, asthma, atopic dermatitis, hay fever, sinusitis, systemic sclerosis, and other allergic diseases; hearing loss, tinnitus, vocal cord fatigue, and other otolaryngological disorders; ALS, Parkinson's disease, post-stroke sequelae, and other neurological disorders; pancreatitis, ulcerative colitis, hepatitis, and other inflammatory diseases.TwX is an antioxidant formulation that can be safely used in both clinical and basic research, and it is expanding significantly in the field of antioxidant therapy, which has previously been challenging. In terms of HSP research, it is anticipated that combining OS stimulation with TwX will promote HSP research.



13:20: [OxidativeThuPM102] OS Keynote
THE POTENTIAL EFFECTS OF ANTIOXIDANT SUPPLEMENTS ON MALE INFERTILITY
Fuhua Yang1; Yoshiaki Harakawa1; Kentaro Omoya1; Haruhiko Inufusa1
1Gifu University, Gifu, Japan
Paper ID: 140 [Abstract]

In recent years, alongside the trend towards postponed marriage and childbirth, factors such as diets high in additives, increased pesticide use, and changes in lifestyle and living environments have contributed to an increasing trend in infertility compared to previous years. While infertility has traditionally been considered to attribute to female factors, it is now proven that approximately half of cases are attributable to male factors. The involvement of oxidative stress (OS) has been indicated as a factor behind this. We investigated the effects of evidence-based antioxidants on male infertility. 

Orthophenyl phenol (OPP) is a fungicide used on citrus fruits. Exposure to OPP through contact with the fruit or the fungicide itself has been reported to increase OS in the body. In this study, long-term exposure to OPP showed an upward trend in OS in the sperm, the testes and the cauda epididymis, with a significant increase in sperm. Furthermore, Claudin1, a tight junction-associated protein found in the testes and the cauda epididymis, demonstrated a downward trend, indicating that elevated OS may result in testicular dysfunction or spermatogenesis disorders. In contrast, the group administered the antioxidant supplement Twendee X (TwX) suppressed the effects of OS. Furthermore, when TwX and Twendee Mtcontrol (TwM), which contains TwX plus seven additional ingredients, were administered to men and women with infertility for six months to one year, both TwX and TwM improved human male function. Notably, the pregnancy rate in the TwM group exceeded 30% after one year. The antioxidant supplements TwX and TwM was suggested to possess the potential to enhance male fertility, thereby improving infertility.

References:
[1] Tournaye, H.; Krausz, C.; Oates, R.D. Novel concepts in the aetiology of male reproductive impairment. Lancet Diabetes Endocrinol. 2017, 5, 544-553. doi:10.1016/S2213-8587(16)30040-7
[2] Krausz, C.; Riera-Escamilla, A. Genetics of male infertility. Nat Rev Urol. 2018, 15, 369–384. doi: 10.1038/s41585-018-0003-3.
[3] Shrilatha, B.; Muralidhara. Early oxidative stress in testis and epididymal sperm in streptozotocin-induced diabetic mice: its progression and genotoxic consequences. Reprod Toxicol. 2007, 23, 578–587. Doi:10.1016/j.reprotox.2007.02.001
[4] Fraga, C.G.; Motchnik, P.A.; Wyrobek, A.J.; Rempel, D.M.; Ames, B.N. Smoking and low antioxidant levels increase oxidative damage to sperm DNA. Mutat Res. 1996, 351, 199-203. doi:10.1016/0027-5107(95)00251-0
[5] Doreswamy, K.; Shrilatha, B.; Rajeshkumar, T.; Muralidhara. Nickel-induced oxidative stress in testis of mice: evidence of DNA damage and genotoxic effects. J Androl. 2004, 25, 996-1003. doi:10.1002/j.1939-4640.2004.tb03173.x


13:40: [OxidativeThuPM103] OS Keynote
POTENTIAL OF ANTIOXIDANT TREATMENT FOR GREY HAIR AND HAIR LOSS
Yoshiaki Harakawa1; Fuhua Yang1; Kentaro Omoya1; Haruhiko Inufusa1
1Gifu University, Gifu, Japan
Paper ID: 130 [Abstract]

Human hair has various functions, including physical protection, insulation, and waste disposal function for the head. It also plays a significant role in social and aesthetic aspects. In many cultures, hair loss and greying are seen as undesirable signs of aging because they contradict the desire to appear younger.
In healthy individuals, around 90 hairs are shed daily and replaced by new hair within 4–6 months; however, factors such as lifestyle habits, stress and hormonal changes can disrupt this cycle, resulting in increased hair loss or delayed growth. Grey hair, on the other hand, occurs when melanocytes — cells that produce melanin, the pigment that gives hair its color — are damaged and can no longer produce melanin. Both conditions are known to be significantly influenced by oxidative stress.
Twendee X and Twendee M are mixed antioxidant supplements composed of vitamins and amino acids, for which safety tests have been conducted. Previous studies have shown that these supplements reduce oxidative stress in the body through their mitochondrial protective effects. In this presentation, we will discuss the potential of antioxidant treatment for grey hair and hair loss based on antioxidant data from the Twendee series, as well as questionnaire results and case reports from human participants.

References:
[1] Seiberg M. Age-induced hair greying - the multiple effects of oxidative stress. Int J Cosmet Sci. 2013 Dec;35(6):532-8.
[2] Trüeb RM. The impact of oxidative stress on hair. Int J Cosmet Sci. 2015 Dec;37 Suppl 2:25-30.
[3] You F, Harakawa Y, Yoshikawa T, Inufusa H. Why Does the Antioxidant Complex Twendee X® Prevent Dementia? Int J Mol Sci. 2023 Aug 21;24(16):13018.


14:00: [OxidativeThuPM104] OS Plenary
ANTIOXIDANT TREATMENT FOR HYPERTHYROIDISM
Yoshiaki Harakawa1; Fuhua Yang1; Kentaro Omoya1; Haruhiko Inufusa1
1Gifu University, Gifu, Japan
Paper ID: 234 [Abstract]

Hyperthyroidism is a general term for a group of disorders characterized by an excessive secretion of thyroid hormones, which affect many vital bodily functions, leading to an accelerated rate of important bodily processes. The causes include Graves' disease, the most common form, toxic multinodular goiter, and thyroiditis, among others. In all cases, patients with this disorder experience increased oxidative stress in the body, which is known to be deeply involved in the pathogenesis of the disease. Furthermore, mitochondria are a primary target of oxidative stress and may contribute to tissue dysfunction associated with hyperthyroidism.

Twendee X (TwX) is an antioxidant supplement containing vitamins, amino acids, and CoQ10. It has passed pharmaceutical-grade safety tests and previous studies have shown that it reduces oxidative stress and protects mitochondrial function. In a case study of patients with Graves' disease who took TwX, elevated thyroid hormone levels normalized shortly after supplementation. TwX shows promise as a safe, antioxidant-based treatment for hyperthyroidism.

References:
[1] Venditti P, Di Meo S. Thyroid hormone-induced oxidative stress. Cell Mol Life Sci. 2006;63(4):414-434.
[2] Bianchi G, Solaroli E, Zaccheroni V, et al. Oxidative stress and anti-oxidant metabolites in patients with hyperthyroidism: effect of treatment. Horm Metab Res. 1999;31(11):620-624.
[3] You F, Harakawa Y, Yoshikawa T, Inufusa H. Why Does the Antioxidant Complex Twendee X® Prevent Dementia? Int J Mol Sci. 2023 Aug 21;24(16):13018.


14:20 POSTERS - Ballroom Foyer