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Total 1197 results found since Jan 2013.

ROMP- and RAFT-based Guanidinium-containing Polymers as Scaffolds for Protein Mimic Synthesis.
Abstract Cell-penetrating peptides are an important class of molecules with promising applications in bioactive cargo delivery. A diverse series of guanidinium-containing polymeric cell-penetrating peptide mimics (CPPMs) with varying backbone chemistries was synthesized and assessed for delivery of both GFP and fluorescently tagged siRNA. Specifically, we examined CPPMs based on norbornene, methacrylate, and styrene backbones to determine how backbone structure impacted internalization of these two cargoes. Either charge content or degree of polymerization was held constant at 20, with di-guanidinium norbornene mo...
Source: Chemistry - March 28, 2017 Category: Chemistry Authors: Tew GN, Sarpas JM, Backland CM, deRonde BM, Minter LM Tags: Chemistry Source Type: research

Molecules, Vol. 23, Pages 777: Polymer-Mediated Delivery of siRNAs to Hepatocellular Carcinoma: Variables Affecting Specificity and Effectiveness
Lucia Scarabel Marica Garziera Concetta Russo Spena Lucia De Stefano Barbara Salis Giuseppe Toffoli Flavio Rizzolio Gabriele Grassi Barbara Dapas Despite the advances in anticancer therapies, their effectiveness for many human tumors is still far from being optimal. Significant improvements in treatment efficacy can come from the enhancement of drug specificity. This goal may be achieved by combining the use of therapeutic molecules with tumor specific effects and delivery carriers with tumor targeting ability. In this regard, nucleic acid-based drug (NABD) and particularly small interfering RNAs (siR...
Source: Molecules - March 28, 2018 Category: Chemistry Authors: Rossella Farra Francesco Musiani Francesca Perrone Maja Čemažar Ur ška Kamenšek Federica Tonon Michela Abrami Ale š Ručigaj Mario Grassi Gabriele Pozzato Deborah Bonazza Fabrizio Zanconati Giancarlo Forte Maguie El Boustani Lucia Scarabel Marica Gar Tags: Review Source Type: research

Structural and functional analyses reveal the contributions of the C- and N-lobes of Argonaute protein to selectivity of RNA target cleavage RNA
Some gene transcripts have cellular functions as regulatory noncoding RNAs. For example, ∼23-nucleotide (nt)–long siRNAs are loaded into Argonaute proteins. The resultant ribonucleoprotein assembly, the RNA-induced silencing complex (RISC), cleaves RNAs that are extensively base-paired with the loaded siRNA. To date, base complementarity is recognized as the major determinant of specific target cleavage (or slicing), but little is known about how Argonaute inspects base pairing before cleavage. A hallmark of Argonaute proteins is their bilobal structure, but despite the significance of this structure for curtailing sli...
Source: Journal of Biological Chemistry - April 27, 2018 Category: Chemistry Authors: Daniel M. Dayeh, Bradley C. Kruithoff, Kotaro Nakanishi Tags: RNA Source Type: research

SERPINA3 Silencing Inhibits the Migration, Invasion, and Liver Metastasis of Colon Cancer Cells.
CONCLUSION: SERPINA3 silencing could inhibit the migration, invasion, and liver metastasis of colon cancer cells. PMID: 29855767 [PubMed - as supplied by publisher]
Source: Anal Sci - May 31, 2018 Category: Chemistry Authors: Cao LL, Pei XF, Qiao X, Yu J, Ye H, Xi CL, Wang PY, Gong ZL Tags: Dig Dis Sci Source Type: research

Molecules, Vol. 24, Pages 1377: Regulation of the Nrf2 Pathway by Glycogen Synthase Kinase-3 β in MPP+-Induced Cell Damage
Molecules, Vol. 24, Pages 1377: Regulation of the Nrf2 Pathway by Glycogen Synthase Kinase-3β in MPP+-Induced Cell Damage Molecules doi: 10.3390/molecules24071377 Authors: Armagan Sevgili Gürkan Köse Bilgiç Dagcı Saso Recently, nuclear translocation and stability of nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) have gained increasing attention in the prevention of oxidative stress. The present study was aimed to evaluate the regulatory role of glycogen synthase kinase-3β (GSK-3β) inhibition by tideglusib through the Nrf2 pathway in a cellular damage mod...
Source: Molecules - April 7, 2019 Category: Chemistry Authors: Armagan Sevgili G ürkan K öse Bilgi ç Dagc ı Saso Tags: Article Source Type: research

The myotubularin MTMR4 regulates phagosomal phosphatidylinositol 3-phosphate turnover and phagocytosis Cell Biology
In conclusion, our findings indicate that MTMR4 regulates PtdIns(3)P degradation in macrophages and thereby controls phagocytosis and phagosomal maturation.
Source: Journal of Biological Chemistry - November 7, 2019 Category: Chemistry Authors: David A. Sheffield, Malene R. Jepsen, Sandra J. Feeney, Micka C. Bertucci, Absorn Sriratana, Monica J. Naughtin, Jennifer M. Dyson, Ross L. Coppel, Christina A. Mitchell Tags: Cell Biology Source Type: research

Preparation of poly(glutamic acid) shielding micelles self-assembled from polylysine-b-polyphenylalanine for gene and drug codelivery
Publication date: Available online 19 February 2020Source: Chinese Chemical LettersAuthor(s): Jing Ma, Jingpeng Zhang, Lin Chi, Chong Liu, Yanhui Li, Huayu TianABSTRACTA novel amphiphilic cationic block copolymer polylysine-b-polyphenylalanine (PLL-b-PPhe) was synthesized and self-assembled into micelles in aqueous solution, then shielded with poly(glutamic acid) (marked as PG/PLL-b-PPhe) to codeliver gene and drug for combination cancer therapy. Here, doxorubicin (DOX) was selected to be loaded into PLL-b-PPhe micelles and the drug loading efficiency was 8.0%. The drug release studies revealed that the PLL-b-PPhe micelles...
Source: Chinese Chemical Letters - February 19, 2020 Category: Chemistry Source Type: research

Molecules, Vol. 28, Pages 4204: Triggering RNA Interference by Photoreduction under Red Light Irradiation
khir RNA interference (RNAi) using small interfering RNAs (siRNAs) is a powerful tool to target any protein of interest and is becoming more suitable for in vivo applications due to recent developments in RNA delivery systems. To exploit RNAi for cancer treatment, it is desirable to increase its selectivity, e.g., by a prodrug approach to activate the siRNAs upon external triggering, e.g., by using light. Red light is especially well suited for in vivo applications due to its low toxicity and higher tissue penetration. Known molecular (not nanoparticle-based) red-light-activatable siRNA prodrugs rely on singlet oxygen ...
Source: Molecules - May 20, 2023 Category: Chemistry Authors: Jennifer R ühle Insa Klemt Andriy Mokhir Tags: Article Source Type: research

eNOS Masquerades as iNOS in Inflamed Endothelium Cell Biology
High levels of NO generated in the vasculature under inflammatory conditions are usually attributed to inducible nitric-oxide synthase (iNOS), but the role of the constitutively expressed endothelial NOS (eNOS) is unclear. In normal human lung microvascular endothelial cells (HLMVEC), bradykinin (BK) activates kinin B2 receptor (B2R) signaling that results in Ca2+-dependent activation of eNOS and transient NO. In inflamed HLMVEC (pretreated with interleukin-1β and interferon-γ), we found enhanced binding of eNOS to calcium-calmodulin at basal Ca2+ levels, thereby increasing its basal activity that was dependent on extrac...
Source: Journal of Biological Chemistry - February 8, 2013 Category: Chemistry Authors: Lowry, J. L., Brovkovych, V., Zhang, Y., Skidgel, R. A. Tags: Signal Transduction Source Type: research

Role of p21WAF1 in IL-20-induced Migration Cell Biology
The role of inflammatory cytokine interleukin-20 (IL-20) has not yet been studied in cancer biology. Here, we demonstrated up-regulation of both IL-20 and IL-20R1 in muscle-invasive bladder cancer patients. The expressions of IL-20 and IL-20R1 were observed in bladder cancer 5637 and T-24 cells. We found that IL-20 significantly increased the expression of matrix metalloproteinase (MMP)-9 via binding activity of NF-κB and AP-1 in bladder cancer cells and stimulated the activation of ERK1/2, JNK, p38 MAPK, and JAK-STAT signaling. Among the pathways examined, only ERK1/2 inhibitor U0126 significantly inhibited IL-20-induced...
Source: Journal of Biological Chemistry - February 22, 2013 Category: Chemistry Authors: Lee, S.-J., Cho, S.-C., Lee, E.-J., Kim, S., Lee, S.-B., Lim, J.-H., Choi, Y. H., Kim, W.-J., Moon, S.-K. Tags: Immunology Source Type: research

STCH Regulates the Functional Expression of NBCe1-B and NHE1 Membrane Biology
In conclusion, we identify a novel role of STCH in the regulation of pHi through site-specific interactions with NBCe1-B and NHE1 and subsequent modulation of membrane transporter expression. We propose STCH may play a role in pHi regulation at times of cellular stress by enhancing the recovery from intracellular acidification.
Source: Journal of Biological Chemistry - March 1, 2013 Category: Chemistry Authors: Bae, J.-S., Koo, N.-Y., Namkoong, E., Davies, A. J., Choi, S.-K., Shin, Y., Jin, M., Hwang, S.-M., Mikoshiba, K., Park, K. Tags: Cell Biology Source Type: research

Prostasin Enhances Matriptase-mediated Intestinal Barrier Cell Biology
The type II transmembrane serine protease matriptase is a key regulator of epithelial barriers in skin and intestine. In skin, matriptase acts upstream of the glycosylphosphatidylinositol-anchored serine protease, prostasin, to activate the prostasin zymogen and initiate a proteolytic cascade that is required for stratum corneum barrier functionality. Here, we have investigated the relationship between prostasin and matriptase in intestinal epithelial barrier function. We find that similar to skin, matriptase and prostasin are components of a common intestinal epithelial barrier-forming pathway. Depletion of prostasin by s...
Source: Journal of Biological Chemistry - April 12, 2013 Category: Chemistry Authors: Buzza, M. S., Martin, E. W., Driesbaugh, K. H., Desilets, A., Leduc, R., Antalis, T. M. Tags: Enzymology Source Type: research

Leucine Increases Insulin Sensitivity through G{alpha}i Proteins Signal Transduction
In this study, we addressed the direct effect of leucine on insulin signaling. In investigating the associated mechanisms, we found that leucine itself does not activate the classical Akt- or ERK1/2 MAP kinase-dependent signaling pathways but can facilitate the insulin-induced phosphorylations of Akt473 and ERK1/2 in a time- and dose-dependent manner in cultured hepatocytes. The leucine-facilitated insulin-induced phosphorylation of Akt at residue 473 was not affected by knocking down the key component of mTORC1 or -2 complexes but was blocked by inhibition of c-Src (PP2), PI3K (LY294002), Gαi protein (pertussis toxin or ...
Source: Journal of Biological Chemistry - March 29, 2013 Category: Chemistry Authors: Yang, X., Mei, S., Wang, X., Li, X., Liu, R., Ma, Y., Hao, L., Yao, P., Liu, L., Sun, X., Gu, H., Liu, Z., Cao, W. Tags: Metabolism Source Type: research

PKC{iota}/Dvl2 in Wnt3a-dependent Neurite Outgrowth Cell Biology
Previously we reported that Wnt3a-dependent neurite outgrowth in Ewing sarcoma family tumor cell lines was mediated by Frizzled3, Dishevelled (Dvl), and c-Jun N-terminal kinase (Endo, Y., Beauchamp, E., Woods, D., Taylor, W. G., Toretsky, J. A., Uren, A., and Rubin, J. S. (2008) Mol. Cell. Biol. 28, 2368–2379). Subsequently, we observed that Dvl2/3 phosphorylation correlated with neurite outgrowth and that casein kinase 1δ, one of the enzymes that mediate Wnt3a-dependent Dvl phosphorylation, was required for neurite extension (Greer, Y. E., and Rubin, J. S. (2011) J. Cell Biol. 192, 993–1004). However, the functional ...
Source: Journal of Biological Chemistry - March 29, 2013 Category: Chemistry Authors: Greer, Y. E., Fields, A. P., Brown, A. M. C., Rubin, J. S. Tags: Signal Transduction Source Type: research

Suppression of TRPC6 Expression by NF-{kappa}B Cell Biology
This study was carried out to explore the molecular mechanism for down-regulation of TRPC6 expression in the reactive oxygen species (ROS)/PKC signaling in kidney cells. In cultured human mesangial cells, H2O2 and TNF-α inhibited TRPC6 mRNA expression in a time-dependent manner. Inhibition of NF-κB reversed both H2O2- and phorbol 12-myristate 13-acetate (PMA)-induced decrease in TRPC6 protein expression. Activation of NF-κB by knocking down IκBα using siRNA could mimic the suppressive effect of ROS/PKC on TRPC6. a Ca2+ imaging study showed that activation and inhibition of NF-κB significantly decreased and increased ...
Source: Journal of Biological Chemistry - May 3, 2013 Category: Chemistry Authors: Wang, Y., Ding, M., Chaudhari, S., Ding, Y., Yuan, J., Stankowska, D., He, S., Krishnamoorthy, R., Cunningham, J. T., Ma, R. Tags: Signal Transduction Source Type: research