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AbstractBackgroundNonalcoholic fatty liver disease (NAFLD) is the most common type of liver disease, but it is difficult to distinguish its pathogenic phenotype, nonalcoholic steatohepatitis (NASH), from nonalcoholic fatty liver (NAFL) without a liver biopsy. We analyzed serum lipids, including low-density lipoprotein triglyceride (LDL-TG), to elucidate their usefulness for diagnosing NASH.Patients and MethodsSerum samples obtained from 35 NASH and 9 NAFL biopsy-confirmed patients and 6 healthy volunteers (HLT) were studied for 13 lipid-related markers and compared between HLT, NAFL, and NASH groups. The relationship between histological findings and the lipid markers was also analyzed.ResultsThere were significant differences in triglyceride, LDL-TG, the ratio of LDL-TG to the LDL-cholesterol (LDL-TG/LDL-C), small dense LDL-C, and apolipoprotein E between the three groups. Among the 5 lipid components, serum LDL-TG level and the ratio of LDL-TG to the LDL-cholesterol (LDL-TG/LDL-C) were significantly elevated in NASH. The median concentrations of LDL-TG in HLT, NAFL, and NASH were 9, 15, and 20 mg/dL (P < 0.001), and those of LDL-TG/LDL-C were 0.097, 0.102, and 0.173 (P < 0.001), respectively. Although the degree of steatosis was not correlated with the LDL-TG/LDL-C, the ratio was significantly higher in patients with lobular inflammation (P = 0.071), ballooning (P = 0.031), and fibrosis (P < 0.001). The area under the receiver operating characteristic curve of the ratio for distinguishing NASH from NAFL was 0.857. The rest of studied markers showed no significant utility.ConclusionSerum LDL-TG levels and the LDL-TG/LDL-C ratio might serve as simple and noninvasive diagnostic biomarkers for NASH.

01 Oct 2020·Nephrology Dialysis TransplantationQ2 · MEDICINE

Chronic hypoxia exacerbates diabetic glomerulosclerosis through mesangiolysis and podocyte injury in db/db mice

Q2 · MEDICINE

Article

Author: Kamiyama, Kazuko ; Hara, Masanori ; Kasuno, Kenji ; Hirayama, Yoshiaki ; Imura, Toshio ; Yokoi, Seiji ; Takahashi, Naoki ; Sugimoto, Hidehiro ; Yoshida, Haruyoshi ; Mikami, Daisuke ; Naiki, Hironobu ; Iwano, Masayuki ; Kurosawa, Hiroyuki ; Kurose, Tomomi ; Kimura, Hideki

AbstractBackgroundChronic hypoxia may play a pivotal role in the development of diabetic nephropathy (DN). However, the precise mechanisms underlying progressive hypoxia-induced glomerular injury remain unclear.MethodsWe housed db/db mice in a hypoxia chamber (12% O2) for up to 16 weeks beginning at 8 weeks of age. Various urine, serum and kidney abnormalities and glomerular messenger RNA (mRNA) expression were compared with those in age-matched db/db mice housed under normoxia.ResultsLevels of urinary albumin and podocalyxin (PCX) were significantly higher in hypoxic mice early during hypoxia. Ultracentrifugation of urine samples revealed that podocytes in the hypoxic mice shed PCX-positive microparticles into the urine. After 16 weeks of hypoxia, the mice also had higher hematocrits with lower serum glucose and various degrees of mesangiolytic glomerulosclerosis with microaneurysms and the infrequent occurrence of nodular lesions. Immunohistologically, hypoxic mice showed significantly decreased endothelial cell densities early during hypoxia and decreased podocyte densities later. In both hypoxic and normoxic mice, glomerular macrophage and transforming growth factor-β1 (TGF-β1) staining significantly increased with aging, without changes in vascular endothelial growth factor or endothelial nitric oxide synthase (eNOS). Glomerular mRNA expression of monocyte chemoattractant protein-1, eNOS and TGF-β1 was significantly enhanced in the hypoxic mice.ConclusionsThese results indicate that chronic hypoxia induces advanced glomerulosclerosis with accelerated albuminuria triggered by mesangiolysis and podocyte injury in a murine model of DN.

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100 Translational Medicine associated with Denka Seiken Co., Ltd.

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Pipeline

Pipeline Snapshot as of 30 Nov 2024

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

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Current Projects

Drug(Targets)	Indications	Global Highest Phase

Influenza virus vaccine(Denka Seiken Co., Ltd.)	Influenza, Human More	Approved
Influenza A virus H5N1 vaccine(Denka Seiken Co., Ltd.)	Influenza A virus infection More	Approved