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1.
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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Anna Stasiowicz Natalia Rosiak Ewa Tykarska Maciej Kozak Jacek Jenczyk Piotr Szulc Joanna Kobus-Cisowska Kornelia Lewandowska Anita Paziska Wojciech Paziski Judyta Cielecka-Piontek 《International journal of molecular sciences》2021,22(8)
Piperine is an alkaloid that has extensive pharmacological activity and impacts other active substances bioavailability due to inhibition of CYP450 enzymes, stimulation of amino acid transporters and P-glycoprotein inhibition. Low solubility and the associated low bioavailability of piperine limit its potential. The combination of piperine with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) causes a significant increase in its solubility and, consequently, an increase in permeability through gastrointestinal tract membranes and the blood–brain barrier. X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FT-IR), nuclear magnetic resonance (NMR) were used to characterize interactions between piperine and HP-β-CD. The observed physicochemical changes should be combined with the process of piperine and CD system formation. Importantly, with an increase in solubility and permeability of piperine as a result of interaction with CD, it was proven to maintain its biological activity concerning the antioxidant potential (2,2-diphenyl-1-picryl-hydrazyl-hydrate assay), inhibition of enzymes essential for the inflammatory process and for neurodegenerative changes (hyaluronidase, acetylcholinesterase, butyrylcholinesterase). 相似文献
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Dr. Tomasz Ratajczyk Prof. Dr. Gerd Buntkowsky Dr. Torsten Gutmann Dr. Bartłomiej Fedorczyk Dr. Adam Mames Dr. Mariusz Pietrzak Zuzanna Puzio Piotr Grzegorz Szkudlarek 《Chembiochem : a European journal of chemical biology》2021,22(5):855-860
The biorelevant PyFALGEA oligopeptide ligand, which is selective towards the epidermal growth factor receptor (EGFR), has been successfully employed as a substrate in magnetic resonance signal amplification by reversible exchange (SABRE) experiments. It is demonstrated that PyFALGEA and the iridium catalyst IMes form a PyFALGEA:IMes molecular complex. The interaction between PyFALGEA:IMes and H2 results in a ternary SABRE complex. Selective 1D EXSY experiments reveal that this complex is labile, which is an essential condition for successful hyperpolarization by SABRE. Polarization transfer from parahydrogen to PyFALGEA is observed leading to significant enhancement of the 1H NMR signals of PyFALGEA. Different iridium catalysts and peptides are inspected to discuss the influence of their molecular structures on the efficiency of hyperpolarization. It is observed that PyFALGEA oligopeptide hyperpolarization is more efficient when an iridium catalyst with a sterically less demanding NHC ligand system such as IMesBn is employed. Experiments with shorter analogues of PyFALGEA, that is, PyLGEA and PyEA, show that the bulky phenylalanine from the PyFALGEA oligopeptide causes steric hindrance in the SABRE complex, which hampers hyperpolarization with IMes. Finally, a single-scan 1H NMR SABRE experiment of PyFALGEA with IMesBn revealed a unique pattern of NMR lines in the hydride region, which can be treated as a fingerprint of this important oligopeptide. 相似文献
6.
Teresa Glomb Benita Wiatrak Katarzyna Gbczak Tomasz Gbarowski Dorota Bodetko aneta Czynikowska Piotr
witek 《International journal of molecular sciences》2020,21(23)
Numerous studies have confirmed the coexistence of oxidative stress and inflammatory processes. Long-term inflammation and oxidative stress may significantly affect the initiation of the neoplastic transformation process. Here, we describe the synthesis of a new series of Mannich base-type hybrid compounds containing an arylpiperazine residue, 1,3,4-oxadiazole ring, and pyridothiazine-1,1-dioxide core. The synthesis was carried out with the hope that the hybridization of different pharmacophoric molecules would result in a synergistic effect on their anti-inflammatory activity, especially the ability to inhibit cyclooxygenase. The obtained compounds were investigated in terms of their potencies to inhibit cyclooxygenase COX-1 and COX-2 enzymes with the use of the colorimetric inhibitor screening assay. Their antioxidant and cytotoxic effect on normal human dermal fibroblasts (NHDF) was also studied. Strong COX-2 inhibitory activity was observed after the use of TG6 and, especially, TG4. The TG11 compound, as well as reference meloxicam, turned out to be a preferential COX-2 inhibitor. TG12 was, in turn, a non-selective COX inhibitor. A molecular docking study was performed to understand the binding interaction of compounds at the active site of cyclooxygenases. 相似文献
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The expression of cytokeratins (CK), involucrin, vimentin, CD34, and alpha-smooth-muscle actin was studied in fetal and adult hair follicles. The first stage of the developing hair follicle is characterized by palisaded, elongated epithelial cells budding from the epidermal basal layer. These cells express CK5/6, CK14, CK17, CK19, and vimentin. During the following weeks of gestation, different structures in the developing hair follicle can be identified and characterized. The matrical cells display only CK19. The keratinocytes of the outer root sheath express CK5/6, CK14, CK17, CK19, and involucrin; those of the inner root sheath, CK4, CK18, and involucrin; those of the isthmus, the same profile as the ORS. In the infundibulum, the basal-layer keratinocytes express CK5/6, CK14, CK17, and CK19, whereas in the suprabasal layers CK1, CK4, CK10, CK14, and CK17 are seen. The adult hair follicle in anagen fails to express CK19 in the matrical cells and isthmus and both CK17 and CK19 in the infundibulum. These profiles of intermediate filaments and other markers appear to be potentially useful in categorizing neoplasms with apparent follicular differentiation. 相似文献
10.
K Ku K Nakayama Y Saitoh S Nosaka T Kitano T Hanada H Nagami K Yamada K Minami 《Canadian Metallurgical Quarterly》1997,64(2):399-403
Forty-eight Russell's viper bite patients (40 males, 8 females), age ranging from 16-76 years were studied. Out of 48 patients, 14 were found to have a prolonged whole blood clotting time test (WBCT) (i.e. incoagulable blood) (Group 1); 23 had a normal WBCT (i.e. clotted blood) (Group II); and 11 patients had a normal WBCT on admission which changed to non-clotting during the clinical course (Group III). Four patients from group I developed hypotension and 2 expired. The serum cortisol concentration (mean +/- SEM) on admission among groups I and II were 639 +/- 45.6 and 424 +/- 33.2 nmol/l respectively. The blood cortisol level in 35 subjects (controls) were 370.7 +/- 17.7 nmol/l (mean +/- SEM). There was a significant rise of blood cortisol in patients with incoagulable blood when compared to controls at the time of admission to the hospital (p < 0.05); but there was no significant difference among those patients with clotted blood. A much higher mean serum cortisol level was observed in 4 patients with hypotension as compared to 10 patients without shock. These patients with hypotension according to our study shown to have a favorable response to steroid therapy and eventually recovered. Whether higher doses of steroid in addition to antiserum confer extra benefit in suppressing nonspecific venom effects on the pituitary and/or adrenal is not known. 相似文献