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Dev Comp Immunol ; 114: 103845, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32888968


Fish hepcidin genes are generally classified into two groups: hamp1-and hamp2-type isoforms. Hamp1-type hepcidin exhibits iron regulatory and antimicrobial activity, while hamp2-type shows a unique role in the immune response against various pathogens. An iron-regulatory motif exists at the N-terminus of hamp1-type hepcidin; however, the functional effect of this motif in fish is not well understood. Here, cDNA of the barbel steed (Hemibarbus labeo) hepcidin gene was cloned and sequenced. The predicted amino acid sequence comprised a signal peptide, a prodomain, and a mature peptide. Phylogenetic tree analysis revealed that barbel steed hepcidin belongs to the fish HAMP1 cluster and is closely related to Chinese rare minnow (Gobiocypris rarus) hepcidin. Barbel steed hepcidin is constitutively expressed in healthy fish tissues, predominantly in the liver. Following iron dextran treatment or Aeromonas hydrophila infection, expression of barbel steed hepcidin increased significantly in tested tissues. In vivo administration of intact hepcidin mature peptide (hep25) significantly and dose-dependently reduced ferroportin 1 expression, while truncated hepcidin mature peptide (hep20) lacking a QSHLS motif had no such effect. In vitro treatment of barbel steed monocytes/macrophages with hep25, but not hep20, increased the labile iron pool levels. Hep25 and hep20 conferred antibacterial activity only against A. hydrophila and Vibrio vulnificus, with greater activity of the latter at low concentrations. Neither hep25 nor hep20 impaired the cell membrane integrity of A. hydrophila, but could hydrolyze its genomic DNA; lack of a QSHLS motif enables hep20 to have a better hydrolytic effect. In summary, we identified an iron-regulatory motif in a fish species and demonstrated that this motif confers hamp1-type hepcidin iron-regulatory activity, but attenuates its antibacterial activity.

Org Lett ; 22(8): 3215-3218, 2020 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-32216367


Arylboration and arylsilylation reactions of N-(2-iodoaryl)acrylamides with bis(pinacolato)-diboron (B2pin2) or PhMe2Si-Bpin are developed by using simple CuOAc as the sole catalyst. A range of boron- or silane-bearing 3,3'-disubstituted oxindoles are obtained in moderate to excellent yields. The reaction is proposed to proceed via a domino sequence involving intermolecular olefin borylcupration or silylcupration followed by intramolecular coupling of an alkyl-Cu intermediate with aryl iodide.

Oncol Rep ; 2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31524273


Protein phosphorylation plays roles in cell transformation. Numerous protein kinase enzymes actively participate in the formation of various types of cancer by phosphorylating downstream substrates. Aurora­A is a widely known Serine/Threonine (Ser/Thr) oncogenic kinase, which is upregulated in more than twenty types of human cancer. This enzyme phosphorylates a wide range of substrates. For example, Aurora­A induces cell transformation by phosphorylating hepatoma upregulated protein (HURP) at four serine residues, which in turn decreases the phosphorylated levels of cell­growth suppressive Jun N­terminal kinase (p­JNK). Various protein phosphatase enzymes are considered tumor suppressors by the dephosphorylation and consequent inactivation of their oncogenic substrates. Protein phosphatase 1α (PP1α), for instance, acts on Aurora­A by dephosphorylating its substrates. However, the role of PP1α in cancer progression remains ambiguous. PP1α is overexpressed in several cancer tissues, and induces cell apoptosis and differentiation or it inhibits tumor formation in other types of cells. In addition, positive and negative correlations between PP1α expression and lung cancer development have been documented. These observations suggest the differential regulation of PP1α in various cancer tissues, or propose an ambiguous contribution of PP1α to lung cancer development. In order to investigate these contradictory conclusions, it was reported that the chromosomal region covering the PP1α locus was subjected to DNA alterations, such as gain or loss in various human cancer types by a study based on literature search. Upregulation of PP1α was noted in a collection of lung cancer tissues, and was required for the cell transformation of the lung cancer cell line A549. In contrast to this finding, overexpression of ectopic PP1α inhibited cell proliferation in 293T cells. Mechanistic studies revealed that PP1α activated AKT in A549 cells, whereas it further inactivated AKT and disrupted the HURP/JNK signaling cascade in 293T cells. Collectively, the data indicated that PP1α exerted an oncogenic function in lung cancer, while exhibiting various effects on cell transformation in different types of cells via distinct or opposite mechanisms.

Medicine (Baltimore) ; 97(42): e12835, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30334985


The study aims to investigate the association between nonalcoholic fatty liver disease (NAFLD) and osteoporosis.We employed a retrospective cohort study design using the National Health Insurance Research Database in Taiwan. Our study included 2 cohorts: 4318 patients with NAFLD and 17,272 patients without NAFLD for comparison. They were matched by sex and age on the date of enrollment between January 1, 2000 and December 31, 2003. The study population in both groups was observed from the enrollment date until December 31, 2013. The incidence and the risk ratios of subsequent osteoporosis were calculated separately in both cohorts. A Cox proportional hazards model was used to assess the potential confounding variables of NAFLD on the pathogenesis of osteoporosis.The eligible study participants comprised 4318 patients in the NAFLD and 17,272 in control cohorts. The median follow-up duration was 10.7 and 10.83 years in the NAFLD and control groups, respectively. The risk of new-onset osteoporosis was higher in patients with NAFLD than in the comparison cohort. In addition, the difference of the incidence of new-onset osteoporosis remained significant among the 2 cohorts in the follow-up durations of within 1 year and more than 10 years. Patients with NAFLD were 1.35 times more likely to develop subsequent osteoporosis compared with those without NAFLD (95% confidence interval = 1.20-1.53).Our finding indicates that NAFLD might increase the risk of developing new-onset osteoporosis. For earlier detection and intervention, screening for osteoporosis in patients with the NAFLD, especially those with lower income and co-morbid with diabetes mellitus and chronic obstructive pulmonary disease, may be recommended.

Hepatopatia Gordurosa não Alcoólica/complicações , Osteoporose/epidemiologia , Adulto , Idoso , Estudos de Coortes , Bases de Dados Factuais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Osteoporose/etiologia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Taiwan/epidemiologia
World J Gastroenterol ; 20(40): 14895-903, 2014 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-25356049


AIM: To investigate the effect of oridonin on nuclear transcription factors and to study the relationship between biological behavior and inflammatory factors in human pancreatic cancer (BxPC-3) cells. METHODS: BxPC-3 cells were treated with various concentrations of oridonin, and viability curves were generated to test for inhibitory effects of the drug on cells. The expression of cytokines such as interleukin-1ß (IL-1ß), IL-6, or IL-33 was detected in BxPC-3 cell supernatants using an enzyme-linked immunosorbent assay (ELISA), and the protein expression of nuclear transcription factors including nuclear factor κB, activating protein-1, signal transducer and activator of transcription 3, bone morphogenetic protein 2, transforming growth factor ß1 and sma and mad homologues in BxPC-3 cells was detected using Western blot. Carcinoma hallmark-related proteins such as survivin, vascular endothelial growth factor, and matrix metallopeptidase 2 were also detected using immunoblotting, and intra-nuclear IL-33 expression was detected using immunofluorescent staining. RESULTS: Treatment with oridonin reduced the viability of BxPC-3 cells in a dose dependent manner. The cells exhibited reduced growth following treatment with 8 µg/mL oridonin (13.05% ± 3.21%, P < 0.01), and the highest inhibitory ratio was 90.64% ± 0.70%, which was achieved with oridonin at a dose of 32 µg/mL. The IC50 value of oridonin in BxPC-3 cells was 19.32 µg/mL. ELISA analysis revealed that oridonin down-regulated the inflammatory factors IL-1ß, IL-6, and IL-33 in a dose-dependent manner. IL-1ß expression was significantly reduced in the 16 and 32 µg/mL treatment groups compared to the control group (12.97 ± 0.45 pg/mL, 11.17 ± 0.63 pg/mL vs 14.40 ± 0.38 pg/mL, P < 0.01). Similar trends were observed for IL-6 expression, which was significantly reduced in the 16 and 32 µg/mL treatment groups compared to the control group (4.05 ± 0.14 pg/mL vs 4.45 ± 0.43 pg/mL, P < 0.05; 3.95 ± 0.13 pg/mL vs 4.45 ± 0.43 pg/mL, P < 0.01). IL-33 expression was significantly reduced in the 8, 16, and 32 µg/mL treatment groups compared to the control group (911.05 ± 14.18 pg/mL vs 945.25 ± 12.09 pg/mL, P < 0.05; 802.70 ± 11.88 pg/mL, 768.54 ± 10.98 pg/mL vs 945.25 ± 12.09 pg/mL, P < 0.01). Western blot and immunofluorescent staining analyses suggested that oridonin changed the hallmarks and regulated the expression of various nuclear transcription factors. CONCLUSION: The results obtained suggest that oridonin alters the hallmarks of pancreatic cancer cells through the regulation of nuclear transcription factors.

Anti-Inflamatórios/farmacologia , Antineoplásicos/farmacologia , Diterpenos de Caurano/farmacologia , Mediadores da Inflamação/metabolismo , Neoplasias Pancreáticas/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteína Morfogenética Óssea 2/metabolismo , Linhagem Celular Tumoral , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Relação Dose-Resposta a Droga , Regulação para Baixo , Humanos , Concentração Inibidora 50 , NF-kappa B/metabolismo , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/patologia , Fator de Transcrição STAT3/metabolismo , Proteínas Smad/metabolismo , Fator de Transcrição AP-1/metabolismo , Fator de Crescimento Transformador beta1/metabolismo