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31.
Ping-Chi Hsu Jia-Ying Jhong Li-Ping Huang Kuo-Hsin Lee Hsin-Pao Chen Yue-Leon Guo 《International journal of molecular sciences》2021,22(8)
Di(2-ethylhexyl) phthalate (DEHP) is widely used as a plasticizer in the manufacture of polyvinylchloride plastics and has been associated with concerns regarding male reproductive toxicity. In this study, we hypothesized that maternal exposure to DEHP induces transgenerational inheritance of adult-onset adverse reproductive outcomes through the male germline in the F1, F2, and F3 generations of male offspring. Pregnant rats were treated with 5 or 500 mg of DEHP/kg/day through gavage from gestation day 0 to birth. The offspring body weight, anogenital distance (AGD), anogenital index (AGI), sperm count, motility, and DNA fragmentation index (DFI) were measured for all generations. Methyl-CpG binding domain sequencing was performed to analyze sperm DNA methylation status in the F3. DEHP exposure at 500 mg/kg affected AGD, AGI, sperm count, mean DFI, and %DFI in the F1; AGD, sperm count, and mean DFI in the F2; and AGD, AGI, mean DFI, and %DFI in the F3. DEHP exposure at 5 mg/kg affected AGD, AGI, sperm count, and %DFI in the F1; sperm count in the F2; and AGD and AGI in F3. Compared with the control group, 15 and 45 differentially hypermethylated genes were identified in the groups administered 5 mg/kg and 500 mg/kg DEHP, respectively. Moreover, 130 and 6 differentially hypomethylated genes were observed in the groups administered 5 mg/kg and 500 mg/kg DEHP. Overall, these results demonstrated that prenatal exposure to DEHP caused transgenerational epigenetic effects, which may explain the observed phenotypic changes in the male reproductive system. 相似文献
32.
Ji Hye Yang Sae Kwang Ku IL Je Cho Je Hyeon Lee Chang-Su Na Sung Hwan Ki 《International journal of molecular sciences》2021,22(4)
Hepatic fibrosis occurs when liver tissue becomes scarred from repetitive liver injury and inflammatory responses; it can progress to cirrhosis and eventually to hepatocellular carcinoma. Previously, we reported that neoagarooligosaccharides (NAOs), produced by the hydrolysis of agar by β-agarases, have hepatoprotective effects against acetaminophen overdose-induced acute liver injury. However, the effect of NAOs on chronic liver injury, including hepatic fibrosis, has not yet been elucidated. Therefore, we examined whether NAOs protect against fibrogenesis in vitro and in vivo. NAOs ameliorated PAI-1, α-SMA, CTGF and fibronectin protein expression and decreased mRNA levels of fibrogenic genes in TGF-β-treated LX-2 cells. Furthermore, downstream of TGF-β, the Smad signaling pathway was inhibited by NAOs in LX-2 cells. Treatment with NAOs diminished the severity of hepatic injury, as evidenced by reduction in serum alanine aminotransferase and aspartate aminotransferase levels, in carbon tetrachloride (CCl4)-induced liver fibrosis mouse models. Moreover, NAOs markedly blocked histopathological changes and collagen accumulation, as shown by H&E and Sirius red staining, respectively. Finally, NAOs antagonized the CCl4-induced upregulation of the protein and mRNA levels of fibrogenic genes in the liver. In conclusion, our findings suggest that NAOs may be a promising candidate for the prevention and treatment of chronic liver injury via inhibition of the TGF-β/Smad signaling pathway. 相似文献
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Dr. Ala Jo Mingi Kim Dr. Jong In Kim Jaeyoung Ha Yoon Soo Hwang Hyunsung Nam Dr. Injae Hwang Dr. Jae Bum Kim Prof. Seung Bum Park 《ChemMedChem》2021,16(7):1104-1115
Obesity has become a pandemic that threatens the quality of life and discovering novel therapeutic agents that can reverse obesity and obesity-related metabolic disorders are necessary. Here, we aimed to identify new anti-obesity agents using a phenotype-based approach. We performed image-based high-content screening with a fluorogenic bioprobe (SF44), which visualizes cellular lipid droplets (LDs), to identify initial hit compounds. A structure-activity relationship study led us to yield a bioactive compound SB1501, which reduces cellular LDs in 3T3-L1 adipocytes without cytotoxicity. SB1501 induced the expression of gene products that regulate mitochondrial biogenesis and fatty acid oxidation in 3T3-L1 adipocytes. Daily treatment with SB1501 improved the metabolic states of db/db mice by reducing body fat mass, adipose tissue mass, food intake, and increasing glucose tolerance. The anti-obesity effect of SB1501 may result from perturbation of the PGC-1α–UCP1 regulatory axis in inguinal white adipose tissue and brown adipose tissue. These data suggest the therapeutic potential of SB1501 as an anti-obesity agent via modulating mitochondrial activities. 相似文献
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36.
Shannon Lee Scott L. Carnahan Georgiy Akopov Philip Yox Lin-Lin Wang Aaron J. Rossini Kui Wu Kirill Kovnir 《Advanced functional materials》2021,31(16):2010293
Noncentrosymmetric (NCS) tetrel pnictides have recently generated interest as nonlinear optical (NLO) materials due to their second harmonic generation (SHG) activity and large laser damage threshold (LDT). Herein nonmetal-rich silicon phosphides RuSi4P4 and IrSi3P3 are synthesized and characterized. Their crystal structures are reinvestigated using single crystal X-ray diffraction and 29Si and 31P magic angle spinning NMR. In agreement with previous report RuSi4P4 crystallizes in NCS space group P1, while IrSi3P3 is found to crystallize in NCS space group Cm, in contrast with the previously reported space group C2. A combination of DFT calculations and diffuse reflectance measurements reveals RuSi4P4 and IrSi3P3 to be wide bandgap (Eg) semiconductors, Eg = 1.9 and 1.8 eV, respectively. RuSi4P4 and IrSi3P3 outperform the current state-of-the-art infrared SHG material, AgGaS2, both in SHG activity and laser inducer damage threshold. Due to the combination of high thermal stabilities (up to 1373 K), wide bandgaps (≈2 eV), NCS crystal structures, strong SHG responses, and large LDT values, RuSi4P4 and IrSi3P3 are promising candidates for longer wavelength NLO materials. 相似文献
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38.
Dr. Jisook Lee Dr. Nyssa Drinkwater Prof. Sheena McGowan Prof. Peter Scammells 《ChemMedChem》2021,16(1):234-249
Aminopeptidase N (APN/CD13) is a zinc-dependent ubiquitous transmembrane ectoenzyme that is widely present in different types of cells. APN is one of the most extensively studied metalloaminopeptidases as an anti-cancer target due to its significant role in the regulation of metastasis and angiogenesis. Previously, we identified a potent and selective APN inhibitor, N-(2-(Hydroxyamino)-2-oxo-1-(3′,4′,5′-trifluoro-[1,1′-biphenyl]-4-yl)ethyl)-4-(methylsulfonamido)benzamide ( 3 ). Herein, we report the further modifications performed to explore SAR around the S1 subsite of APN and to improve the physicochemical properties. A series of hydroxamic acid analogues were synthesised, and the pharmacological activities were evaluated in vitro. N-(1-(3′-Fluoro-[1,1′-biphenyl]-4-yl)-2-(hydroxyamino)-2-oxoethyl)-4-(methylsulfonamido)benzamide ( 6 f ) was found to display an extremely potent inhibitory activity in the sub-nanomolar range. 相似文献
39.
Jang Hye Ji Kim Jong Ha Lee Hyun-Sook Paik Hyun-Dong 《Food science and biotechnology》2022,31(6):731-737
Food Science and Biotechnology - The objective of this study was to develop a non-fermented probiotic milk that maintains its physicochemical properties, microbial properties, antioxidant activity,... 相似文献
40.