Review
Urology & Nephrology
Laura G. Sanchez-Lozada, Magdalena Madero, Marilda Mazzali, Daniel Feig, Takahiko Nakagawa, Miguel A. Lanaspa, Mehmet Kanbay, Masanari Kuwabara, Bernardo Rodriguez-Iturbe, Richard J. Johnson
Summary: Despite being discovered more than 150 years ago, the cause of primary hypertension remains unknown. Recent studies suggest that fructose metabolism may play a role in the development of primary hypertension. Restricting salt and sugar intake, as well as staying hydrated, may be helpful in preventing primary hypertension.
CLINICAL KIDNEY JOURNAL
(2023)
Review
Peripheral Vascular Disease
Takahiko Nakagawa, Ana Andres-Hernando, Tomoki G. Kosugi, Laura Sanchez-Lozada, Peter Stenvinkel, Karolina Kublickiene, S. Ananth Karumanchi, Duk-Hee Kang, Hideto Kojima, Bernardo R. Rodriguez-Iturbe, Dean A. Tolan, Miguel J. Lanaspa, Richard Johnson
Summary: Preeclampsia is a hypertensive disorder of pregnancy caused by abnormal placentation. Fructose, which plays a critical role in fetal growth, is produced in the placenta during early pregnancy to assist fetal survival in a hypoxic environment. Impaired placentation leads to excessive fructose production, which drives various pathological features of preeclampsia. In addition, dietary fructose intake has been identified as an independent risk factor for preeclampsia.
HYPERTENSION RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Ana Magdalena Velazquez, Roger Bentanachs, Aleix Sala-Vila, Iolanda Lazaro, Jose Rodriguez-Morato, Rosa Maria Sanchez, Juan Carlos Laguna, Nuria Roglans, Marta Alegret
Summary: The study investigated the anti-steatotic effect of Bempedoic acid (BemA) in a rat model of fatty liver induced by a high-fat diet supplemented with liquid fructose. The results showed that BemA-treated rats exhibited lower body weight, higher liver/body weight, and reduced hepatic steatosis compared to the control group. In addition to inhibiting ATP-citrate lyase (ACLY), BemA was found to have three novel mechanisms, including reducing fructose intake and de novo lipogenesis, increasing liver triglyceride export, and promoting hepatic fatty acid beta-oxidation. These findings suggest that BemA may be a potential approach for treating hepatic steatosis and preventing the progression of non-alcoholic fatty liver disease.
Article
Plant Sciences
Muhammad Moaaz Ali, Shaista Gull, Xiaobo Hu, Youming Hou, Faxing Chen
Summary: This study found that spraying loquat trees with 0.1% zinc sulphate resulted in increased levels of soluble sugars and decreased acid contents in loquats. The activities of key enzymes were measured and gene expression analysis revealed the potential involvement of certain enzymes and genes in regulating sugar-acid metabolism in loquats.
PLANT PHYSIOLOGY AND BIOCHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Francesco Balestri, Roberta Moschini, Umberto Mura, Mario Cappiello, Antonella Del Corso
Summary: This article introduces the role of aldose reductase (AKR1B1) in diabetic complications and the development of its inhibitors. Currently, the synthesized inhibitors have failed to become drugs for the treatment of diabetic complications. The article proposes a differential inhibition approach that has the potential to become a new generation of inhibitors.
Article
Chemistry, Multidisciplinary
Aqeel Imran, Muhammad Tariq Shehzad, Syed Jawad Ali Shah, Mark Laws, Taha al-Adhami, Khondaker Miraz Rahman, Imtiaz Ali Khan, Zahid Shafiq, Jamshed Iqbal
Summary: Diabetic complications are caused by overexpression of aldose reductase, leading to oxidative stress and formation of advanced glycation end products. Current aldose reductase inhibitors have failed due to toxicity and poor pharmacokinetic profiles. This study developed thiosemicarbazone derivatives as selective inhibitors of ALR2 with antioxidant and antiglycation potential. Among the synthesized compounds, 3c showed strong and selective inhibition of ALR2, as well as good antioxidant and antiglycative properties.
Article
Nutrition & Dietetics
Francois-Guillaume Debray, Kevin Seyssel, Marjorie Fadeur, Luc Tappy, Nicolas Paquot, Christel Tran
Summary: The study showed that overfeeding on fructose can lead to increased uric acid and insulin resistance, with a more significant impact on carriers of hereditary fructose intolerance.
CLINICAL NUTRITION
(2021)
Article
Chemistry, Multidisciplinary
Alican Kaya, Asli F. Ceylan, Mustafa Kavutcu, Abel Santamaria, Marta Soltesova Prnova, Milan Stefek, Cimen Karasu
Summary: Inhibiting aldose reductase (ALR2, AR) as well as maintaining a concomitant antioxidant (AO) activity via dual-acting agents may be a rational approach to prevent cellular glucotoxicity and at least delay the progression of diabetes mellitus (DM).
DRUG AND CHEMICAL TOXICOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Yeliz Demir, Hamid Ceylan, Cuneyt Turkes, Sukru Beydemir
Summary: The study demonstrates the inhibitory effects of VA, CA, and UA on AR and SDH enzymes, potentially useful in preventing diabetic complications.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Review
Nutrition & Dietetics
Simonetta Genovesi, Marco Giussani, Antonina Orlando, Francesca Orgiu, Gianfranco Parati
Summary: The prevalence of essential arterial hypertension in children and adolescents has increased significantly in recent decades, with incorrect eating habits being one of the contributing factors. Excessive intake of salt and sugar has been linked to the development of hypertension in children, especially those who are overweight. Maintaining correct eating habits is crucial for the prevention and non-drug treatment of essential hypertension in children and adolescents.
Review
Biochemistry & Molecular Biology
Pablo Muriel, Pedro Lopez-Sanchez, Erika Ramos-Tovar
Summary: Chronic diseases, particularly metabolic syndrome and non-alcoholic fatty liver disease (NAFLD), are major health challenges globally, with fructose overconsumption playing a significant role in their development. Fructose-induced inflammation, fibrosis, and oncogenic signaling pathways contribute to the progression of NAFLD, leading to serious liver complications such as NASH and ultimately liver cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Plant Sciences
Pingchang Fang, Xiangyu Long, Yongjun Fang, Hua Chen, Ma Yu
Summary: This study investigated the role of fructokinase in rubber tree, with findings that HbFRK2 exhibited the highest expression level and affinity for fructose in laticifers, indicating a critical role in carbon flow and latex regeneration.
PLANT PHYSIOLOGY AND BIOCHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Xudong Wang, Qingbo Deng, Yi Zhang, Zhilin Ren, Ping He
Summary: Efficient production of 5-hydroxymethylfurfural (5-HMF) from fructose dehydration was achieved using a strong acidic ion-functionalized porous carbon (PCN-ILSO3CF3) as catalyst. The optimized reaction conditions were 110 degrees C for 50 min in DMSO, resulting in full fructose conversion and a 5-HMF yield of 95.6%. The PCN-ILSO3CF3 catalyst exhibited high Bronsted acid density and a super-high surface area of 1400 m(2)/g, enabling selective adsorption of fructose and rapid removal of 5-HMF from the catalyst surface. The catalyst also showed good reusability with 84.0% 5-HMF yield after five runs.
RESEARCH ON CHEMICAL INTERMEDIATES
(2023)
Review
Biology
Richard J. Johnson, Miguel A. Lanaspa, L. Gabriela Sanchez-Lozada, Dean Tolan, Takahiko Nakagawa, Takuji Ishimoto, Ana Andres-Hernando, Bernardo Rodriguez-Iturbe, Peter Stenvinkel
Summary: The fructose survival hypothesis suggests that obesity and metabolic disorders may be caused by excessive stimulation of a biological response triggered by fructose intake. This response involves hunger, thirst, weight gain, fat accumulation, insulin resistance, inflammation, and increased blood pressure. In humans, this response is exaggerated due to genetic factors and a western diet high in fructose. Excessive fructose metabolism not only explains obesity but also various diseases such as diabetes, hypertension, fatty liver disease, obesity-related cancers, vascular and Alzheimer's dementia, and aging. Reducing activation of this pathway and promoting mitochondrial regeneration may improve health-span.
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Himangshu Sonowal, Kota V. Ramana
Summary: Aldose Reductase (AR) is an enzyme involved in the polyol pathway of glucose metabolism and has been associated with the development of secondary diabetic complications as well as inflammatory disorders and cancer. Research is currently focused on exploring the potential therapeutic use of AR inhibitors beyond diabetic complications.
CURRENT MEDICINAL CHEMISTRY
(2021)
Article
Rheumatology
Ruriko Koto, Izumi Sato, Masanari Kuwabara, Tomotsugu Seki, Koji Kawakami
Summary: This study aims to evaluate the association between hypouricemia and cardiometabolic diseases, and explore the optimal range of serum uric acid (sUA) associated with the lowest risk for these diseases, considering the gender difference. The results showed a J-shaped association between sUA levels and cardiometabolic diseases, with excess and extremely low levels being associated with increased risk. The optimal range for the lowest risk of hypertension was assumed to be between 2.1 and 3.0 mg/dL for the overall population, while this association was only observed in women.
JCR-JOURNAL OF CLINICAL RHEUMATOLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Ryusuke Ae, Yoshihide Shibata, Tohru Kobayashi, Koki Kosami, Masanari Kuwabara, Nobuko Makino, Yuri Matsubara, Teppei Sasahara, Hiroya Masuda, Yosikazu Nakamura
Summary: No studies have assessed the differences in echocardiographic detection sensitivity of coronary artery abnormalities between the Japanese and Z score criteria in Kawasaki disease (KD). This study analyzed data from a large-scale survey in Japan and found that the Z score criteria had significantly higher detection sensitivities for CA dilatations and aneurysms compared to the Japanese criteria. The differences in detection sensitivity were dependent on CA size and patient age.
PEDIATRIC CARDIOLOGY
(2023)
Article
Medicine, General & Internal
Makoto Yamaguchi, Masashi Mizuno, Fumiya Kitamura, Shiho Iwagaitsu, Hironobu Nobata, Hiroshi Kinashi, Shogo Banno, Akimasa Asai, Takuji Ishimoto, Takayuki Katsuno, Yasuhiko Ito
Summary: Thrombotic microangiopathy (TMA) and macrophage activation syndrome (MAS) are rare and life-threatening complications of systemic lupus erythematosus (SLE). The association between TMA and MAS in SLE patients has been rarely studied and the diagnosis of these conditions remains challenging. This case report demonstrates the efficacy of eculizumab in treating refractory TMA concurrent with SLE-associated MAS, and suggests the importance of evaluating TMA during the course of SLE-associated MAS.
FRONTIERS IN MEDICINE
(2023)
Article
Urology & Nephrology
Miyoko Kunou, Makoto Yamaguchi, Hirotake Takahashi, Yukihiro Kimura, Naoki Watanabe, Mayumi Ito, Hirokazu Sugiyama, Shiho Iwagaitsu, Hironobu Nobata, Hiroshi Kinashi, Takayuki Katsuno, Shogo Banno, Yasuhiko Ito, Takuji Ishimoto
Summary: Adenine phosphoribosyltransferase (APRT) deficiency, a rare genetic disorder, causes the accumulation of poorly soluble 2,8-dihydroxyadenine (DHA) in the kidneys, leading to various renal problems such as nephrolithiasis, acute kidney injury, and chronic kidney disease (CKD) due to crystal nephropathy. We present a case of a 43-year-old man with 2,8-DHA crystalline nephropathy caused by APRT deficiency, diagnosed definitively by urine gas chromatography-mass spectrometry (GC/MS)-based plasma metabolomics. This case highlights the importance of recognizing the signs, symptoms, and progression of this rare condition to CKD, which can be prevented by early administration of xanthine oxidoreductase inhibitors.
Review
Medicine, General & Internal
Cem Tanriover, Sidar Copur, Abduzhappar Gaipov, Batu Ozlusen, Rustu E. Akcan, Masanari Kuwabara, Mads Hornum, Daniel H. Van Raalte, Mehmet Kanbay
Summary: Obesity is a complex condition with different subtypes, one of which is metabolically healthy obesity (MHO). MHO has various definitions and its prevalence differs in different studies. Mechanisms underlying MHO include adipose tissue types and distribution, hormones, inflammation, diet, microbiota, and genetics. While MHO has relatively favorable metabolic characteristics compared to metabolically unhealthy obesity (MUO), it is still associated with important chronic diseases and has the potential to progress into an unhealthy phenotype. The major treatment options for MHO include dietary modifications, exercise, bariatric surgery, and specific medications.
EUROPEAN JOURNAL OF INTERNAL MEDICINE
(2023)
Article
Peripheral Vascular Disease
Megumi Shimizu, Takatoshi Kasai, Ryo Naito, Akihiro Sato, Sayaki Ishiwata, Shoichiro Yatsu, Jun Shitara, Hiroki Matsumoto, Azusa Murata, Takao Kato, Shoko Suda, Masaru Hiki, Masanari Kuwabara, Takayo Murase, Takashi Nakamura, Hiroyuki Daida
Summary: Serum uric acid (UA) level and sleep-disordered breathing (SDB) are associated with the risk of coronary artery disease (CAD). This study found that SDB severity is correlated with an increase in xanthine oxidoreductase (XOR) activity and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels, suggesting a link between SDB and oxidative stress via UA production. Serum UA levels also significantly increased overnight in male CAD patients. Overall, these findings shed light on the mechanisms linking SDB, hyperuricemia, and CAD.
HYPERTENSION RESEARCH
(2023)
Editorial Material
Peripheral Vascular Disease
Yu Otsu, Ryusuke Ae, Masanari Kuwabara
HYPERTENSION RESEARCH
(2023)
Review
Peripheral Vascular Disease
Masanari Kuwabara, Takahide Kodama, Ryusuke Ae, Mehmet Kanbay, Ana Andres-Hernando, Claudio Borghi, Ichiro Hisatome, Miguel A. Lanaspa
Summary: Many studies have reported a direct relationship between serum uric acid levels and hypertension, cardiovascular, renal, and metabolic diseases. While there is a clinical association between uric acid and high blood pressure, it is still unclear whether lowering uric acid is beneficial for preventing cardiovascular and renal metabolic diseases.
HYPERTENSION RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Ana Andres-Hernando, David J. Orlicky, Christina Cicerchi, Masanari Kuwabara, Gabriela E. Garcia, Takahiko Nakagawa, Laura Gabriela Sanchez-Lozada, Richard J. Johnson, Miguel A. Lanaspa
Summary: Obesity and metabolic syndrome increase the susceptibility to chronic kidney disease (CKD), potentially due to enhanced absorption and utilization of fructose. Pound mice with metabolic syndrome showed increased expression of fructose transporter and fructokinase, leading to enhanced fructose absorption. Administration of high fructose corn syrup (HFCS) rapidly induced CKD in pound mice, whereas pound mice lacking fructokinase were protected from CKD. Lowering added sugar intake may reduce the risk for CKD in subjects with metabolic syndrome.
Article
Nutrition & Dietetics
Makoto Yamaguchi, Mayumi Ito, Hirokazu Sugiyama, Shiho Iwagaitsu, Hironobu Nobata, Hiroshi Kinashi, Takayuki Katsuno, Shogo Banno, Yasuhiko Ito, Masahiko Ando, Yoko Kubo, Keisuke Maeda, Yuria Ishida, Naoharu Mori, Takuji Ishimoto
Summary: A study found that malnutrition based on the GLIM criteria is associated with mortality in patients with cardiovascular disease (CVD), and the severity of malnutrition is positively correlated with mortality. Furthermore, malnutrition combined with renal dysfunction is also positively associated with mortality. These findings provide clinically relevant information for identifying high mortality risk and emphasizing the importance of addressing malnutrition with kidney dysfunction among CVD patients.
CLINICAL NUTRITION ESPEN
(2023)
Review
Biology
Richard J. Johnson, Miguel A. Lanaspa, L. Gabriela Sanchez-Lozada, Dean Tolan, Takahiko Nakagawa, Takuji Ishimoto, Ana Andres-Hernando, Bernardo Rodriguez-Iturbe, Peter Stenvinkel
Summary: The fructose survival hypothesis suggests that obesity and metabolic disorders may be caused by excessive stimulation of a biological response triggered by fructose intake. This response involves hunger, thirst, weight gain, fat accumulation, insulin resistance, inflammation, and increased blood pressure. In humans, this response is exaggerated due to genetic factors and a western diet high in fructose. Excessive fructose metabolism not only explains obesity but also various diseases such as diabetes, hypertension, fatty liver disease, obesity-related cancers, vascular and Alzheimer's dementia, and aging. Reducing activation of this pathway and promoting mitochondrial regeneration may improve health-span.
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
(2023)
Meeting Abstract
Peripheral Vascular Disease
Masanari Kuwabara, Takahide Kodama
JOURNAL OF HYPERTENSION
(2023)
Meeting Abstract
Peripheral Vascular Disease
Masanari Kuwabara, Yuki OhmotoSekine, Hidetaka Itoh, Ichiro Hisatome, Takahide Kodama
JOURNAL OF HYPERTENSION
(2023)
Review
Rheumatology
Seika Terashima, Makoto Yamaguchi, Tomomi Ishihara, Junichiro Hagita, Takayuki Katsuno, Mayumi Ito, Hirokazu Sugiyama, Shiho Iwagaitsu, Hironobu Nobata, Hiroshi Kinashi, Takuji Ishimoto, Shogo Banno, Yasuhiko Ito
Summary: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare disease characterized by inflammation in multiple organ systems, most commonly the lungs, skin, and nervous system. Limb ulcers are a rare complication, and there are few reports on the use of mepolizumab in treating EGPA.
MODERN RHEUMATOLOGY CASE REPORTS
(2023)
