Month: October 2022

Hao, Xueyu; Wang, Chunyu; Wang, Yu; Li, Chunjie; Hou, Jingwei; Zhang, Feng; Kang, Chuanqing; Gao, Lianxun published the artcile< Topological conversion of human telomeric G-quadruplexes from hybrid to parallel form induced by naphthalene diimide ligands>, Name: 7H-Purin-2-amine, the main research area is naphthalene diimide G quadruplex telomere regulation; G-quadruplex; Human telomere; Naphthalene diimide; Topological conversion.

G-quadruplexes (GQs) have become promising anti-cancer therapeutic targets, which are formed by the folding of a guanine-rich repeat DNA/RNA sequence at human telomeres or oncogene promoters. Polymorphism has been observed for the folding topologies of intramol. GQs. Here we report the topol. conversion of human telomeric GQ induced by naphthalene diimide (NDI) ligands in K+ solution The ligands selectively induce metastable hybrid-type GQs to highly stable parallel-type GQ at physiol. temperature (37°C) in dilute aqueous solutions and under crowding conditions that mimic cellular bioenvironment. According to spectroscopic analyses, the topol. conversion is speculated to undergo stepwise unfolding of hybrid-type GQ through intermediate states to parallel-type GQ. The results will prompt further studies on the designs of ligands with GQ conformation regulation functions and nanotechnol. systems based on nucleic acids with dynamic regulation of GQ conformation.

International Journal of Biological Macromolecules published new progress about Animal gene, c-myc Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 452-06-2 belongs to class imidazoles-derivatives, and the molecular formula is C5H5N5, Name: 7H-Purin-2-amine.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Hornum, Mick; Stendevad, Julie; Sharma, Pawan K.; Kumar, Pawan; Nielsen, Rasmus B.; Petersen, Michael; Nielsen, Poul published the artcile< Base-Pairing Properties of Double-Headed Nucleotides>, Electric Literature of 452-06-2, the main research area is base pair double headed nucleotide DNA duplex; 2,6-diaminopurine; double-headed nucleotides; hypoxanthine; oligonucleotides.

Nucleotides that contain two nucleobases (double-headed nucleotides) have the potential to condense the information of two sep. nucleotides into one. This presupposes that both bases must successfully pair with a cognate strand. Here, double-headed nucleotides that feature cytosine, guanine, thymine, adenine, hypoxanthine, and diaminopurine linked to the C2′-position of an arabinose scaffold were developed and examined in full detail. These monomeric units were efficiently prepared by convergent synthesis and incorporated into DNA oligonucleotides by means of the automated phosphoramidite method. Their pairing efficiency was assessed by UV-based melting-temperature anal. in several contexts and extensive mol. dynamics studies. Altogether, the results show that these double-headed nucleotides have a well-defined structure and invariably behave as functional dinucleotide mimics in DNA duplexes.

Chemistry – A European Journal published new progress about DNA-DNA hybridization. 452-06-2 belongs to class imidazoles-derivatives, and the molecular formula is C5H5N5, Electric Literature of 452-06-2.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Yuan, Xiaoqiu; Li, Tiefeng; Shi, Lei; Miao, Jinhao; Guo, Yongfei; Chen, Yu published the artcile< Human umbilical cord mesenchymal stem cells deliver exogenous miR-26a-5p via exosomes to inhibit nucleus pulposus cell pyroptosis through METTL14/NLRP3>, Recommanded Product: p-Benzenediacrylanilide, 4′,4′′-di-2-imidazolin-2-yl-, dihydrochloride, the main research area is miR26a5p METTL14 NLRP3 IGF2BP2 GW4869 nucleus pulposus cell pyroptosis; Exosomal miR-26a-5p; Intervertebral disc degeneration; N6-methyladenosine; Pyroptosis; Umbilical cord mesenchymal stem cells.

Intervertebral disk degeneration (IVDD) is the breakdown of the disks supporting the vertebrae. It is one of the most frequent causes of back pain worldwide. Currently, the clin. interventions for IVDD are mainly focused on symptom releases. Thus, new therapeutic options are needed. Nucleus pulposus (NP) samples were obtained from 20 patients experiencing IVDD and 10 healthy volunteers compared for mRNA N6-methyladenosine (m6A) mRNA modification as well as methyltransferase (METT) like METTL3, METTL14, and Wilms’ tumor 1-associated protein mRNA and protein abundance following exosomes exposure from mesenchymal stem cells. In addition, microRNA expressions were also compared. The correlation between the NLR family pyrin domain containing 3 (NLRP3) and METTL14 was measured by luciferase reporter assay. Cytokines were evaluated using an ELISA. METTL14, NLRP3, and insulin-like growth factor 2 mRNA-binding protein 2 mRNAs were measured via a quant. reverse transcription-polymerase chain reaction. Protein was assayed using western blots. Cell death was assessed by propidium iodide staining, lactate dehydrogenase release, gasdermin-N domain abundance, and caspase-1 activation. The human umbilical cord mesenchymal stem cell (hucMSC) exosomes were found to effectively improve the viability of NP cells and protect them from pyroptosis through targeting METTL14, with a methyltransferase catalyzing m6A modification. METTL14 was highly present in NP cells from IVDD patients, which stabilize NLRP3 mRNA in an IGFBP2-dependent manner. The elevated NLRP3 levels result in the increase of interleukin 1β (IL-1β) and IL-18 levels and trigger pyroptotic NP cell death. Such pathogenic axis could be blocked by hucMSC exosomes, which directly degrade METTL14 through exosomal miR-26a-5p. The results of the current study revealed the beneficial effects of hucMSC exosomes on NP cells and determined a potential mechanism inducing IVDD.

Molecular Medicine (London, United Kingdom) published new progress about 3′-Untranslated region Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 6823-69-4 belongs to class imidazoles-derivatives, and the molecular formula is C30H30Cl2N6O2, Recommanded Product: p-Benzenediacrylanilide, 4′,4′′-di-2-imidazolin-2-yl-, dihydrochloride.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Kaiser, Carl; Spagnuolo, Ciro J.; Adams, Theodore C. Jr.; Audia, Vicki H.; Dupont, Andrea C.; Hatoum, Holia; Lowe, Valerie C.; Prosser, Judith C.; Sturm, Bonnie L.; Noronha-Blob, Lalita published the artcile< Synthesis and antimuscarinic properties of some N-substituted 5-(aminomethyl)-3,3-diphenyl-2(3H)-furanones>, SDS of cas: 36947-69-0, the main research area is aminomethyldiphenylfuranone antimuscarinic structure activity; furanone aminomethyldiphenyl antimuscarinic structure activity; urinary incontinence treatment imidazolylmethyldiphenylfuranone; benactyzine constrained analog structure activity.

In a study aimed toward developing new, selective antimuscarinic drugs with potential utility in the treatment of urinary incontinence associated with bladder muscle instability, a series of N-substituted 5-(aminomethyl)-3,3-diphenyl-2(3H)-furanones I (R = Me, R1 = alkyl, aralkyl; R = R1 = Et, Pr; NRR1 = pyrrolidino, N-methylpiperazino, N-phenylpiperazino, morpholino, substituted imidazol-1-yl, substituted pyrazol-1-yl, triazol-1-yl, substituted imidazopyridin-1-yl, etc.), conformationally-constrained lactone relatives of benactyzine, was prepared The compounds were examined in several paradigms that measure muscarinic (M1, M2, and M3) receptor antagonist activity. Selected members of the series that displayed potency and/or selectivity in these tests were studied for their effects on urinary bladder contraction, mydriasis, and salivation in guinea pigs. These studies revealed that incorporation of the amino functionality into an imidazole or pyrazole ring resulted in some novel, potent, and selective antimuscarinic agents. Appropriate alkyl substitution of position 2 of the imidazole strikingly affected muscarinic, particularly M3, receptor activity and may reflect a complementary site of interaction. Some of the compounds selectively reduced bladder pressure in a cystometrogram (CMG) model without producing concomitant mydriatic and salivary effects. The sep. and distinct action of several compounds of this series in these in vivo protocols suggests the possibility of subtypes of muscarinic receptors that may correspond to previously characterized mol. cloned subpopulations. Structure-activity relationships of this series of substituted lactones are discussed. These studies led to the identification of (R)-isomer II as a clin. candidate for treating urinary bladder dysfunction.

Journal of Medicinal Chemistry published new progress about Muscarinic antagonists. 36947-69-0 belongs to class imidazoles-derivatives, and the molecular formula is C7H12N2, SDS of cas: 36947-69-0.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Wang, Lei; Duan, Lele; Stewart, Beverly; Pu, Maoping; Liu, Jianhui; Privalov, Timofei; Sun, Licheng published the artcile< Toward Controlling Water Oxidation Catalysis: Tunable Activity of Ruthenium Complexes with Axial Imidazole/DMSO Ligands>, Formula: C4H5BrN2, the main research area is controlling water oxidation catalysis tunable activity; ruthenium complex axial imidazole DMSO ligand.

Using the combinations of imidazole and DMSO (DMSO) as axial ligands and 2,2′-bipyridine-6,6′-dicarboxylate (bda) as the equatorial ligand, we have synthesized six novel ruthenium complexes with noticeably different activity as water oxidation catalysts (WOCs). In four Cs sym. RuII(κ3-bda)(DMSO)L2 complexes L = imidazole (1), N-methylimidazole (2), 5-methylimidazole (3), and 5-bromo-N-methylimidazole (4). Addnl., in two C2v sym. RuII(κ4-bda)L2 complexes L = 5-nitroimidazole (5) and 5-bromo-N-methylimidazole (6), i.e., fully equivalent axial imidazoles. A detailed characterization of all complexes and the mechanistic investigation of the catalytic water oxidation have been carried out with a number of exptl. techniques, i.e., kinetics, electrochem. and high resolution mass spectrometry (HR-MS), and d. functional theory (DFT) calculations We have observed the in situ formation of a RuII-complex with the accessible seventh coordination position. The measured catalytic activities and kinetics of complex 1-6 revealed details about an important structure-activity relation: the connection between the nature of axial ligands in the combination and either the increase or decrease of the catalytic activity. In particular, an axial DMSO group substantially increases the turnover frequency of WOCs reported in the article, with the ruthenium-complex having one axial 5-bromo-N-methyl-imidazole and one axial DMSO (4), we have obtained a high initial turnover frequency of ∼180 s-1. DFT modeling of the binuclear reaction pathway of the O-O bond formation in catalytic water oxidation further corroborated the concept of the mechanistic significance of the axial ligands and rationalized the exptl. observed difference in the activity of complexes with imidazole/DMSO and imidazole/imidazole combinations of axial ligands.

Journal of the American Chemical Society published new progress about Bond angle. 1003-21-0 belongs to class imidazoles-derivatives, and the molecular formula is C4H5BrN2, Formula: C4H5BrN2.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Yang, Qianxi; Zhao, Shaorong; Shi, Zhendong; Cao, Lixia; Liu, Jingjing; Pan, Teng; Zhou, Dongdong; Zhang, Jin published the artcile< Chemotherapy-elicited exosomal miR-378a-3p and miR-378d promote breast cancer stemness and chemoresistance via the activation of EZH2/STAT3 signaling>, Reference of 6823-69-4, the main research area is chemotherapy miR378a3p miR378d EZH2 STAT3 signaling breast cancer; Cancer stemness; Chemotherapy resistance; Chemotherapy-elicited exosomes; miR-378a-3p; miR-378d.

Not all breast cancer (BC) patients who receive neoadjuvant chemotherapy achieve a pathol. complete response (pCR), but the reasons for this are unknown. Previous studies have shown that exosomes produced in the tumor microenvironment in response to chemotherapy promote a chemotherapy-resistant phenotype in tumors. However, the role of BC chemotherapy-elicited exosomes in regulating chemoresistance is poorly understood. Using com. kits, serum exosomes were extracted from patients before neoadjuvant chemotherapy, after one cycle of chemotherapy and after four cycles of chemotherapy consisting of doxorubicin (DOX) and paclitaxel (PTX). Their miRNAs were sequenced, and the correlation between the sequencing results and chemotherapy effects was further verified by RT-qPCR using patient serum exosomes. Cell Counting Kit-8 (CCK-8) was used to detect chemosensitivity. Stemness was assessed by CD44+/CD24- population anal. and mammosphere formation assays. Chromatin immunoprecipitation (ChIP) experiments were performed to verify the binding of signal transducer and activator of transcription 3 (STAT3) to the promoter of miRNAs. Here, we provide clin. evidence that chemotherapy-elicited exosomal miR-378a-3p and miR-378d are closely related to the chemotherapy response and that exosomes produced by BC cells after stimulation with DOX or PTX deliver miR-378a-3p and miR-378d to neighboring cells to activate WNT and NOTCH stemness pathways and induce drug resistance by targeting Dickkopf 3 (DKK3) and NUMB. In addition, STAT3, which is enhanced by zeste homolog 2 (EZH2), bound to the promoter regions of miR-378a-3p and miR-378d, thereby increasing their expression in exosomes. More importantly, chemotherapeutic agents combined with the EZH2 inhibitor tazemetostat reversed chemotherapy-elicited exosome-induced drug resistance in a nude mouse tumor xenograft model. This study revealed a novel mechanism of acquired chemoresistance whereby chemotherapy activates the EZH2/STAT3 axis in BC cells, which then secrete chemotherapy-elicited exosomes enriched in miR-378a-3p and miR-378d. These exosomes are absorbed by chemotherapy-surviving BC cells, leading to activation of the WNT and NOTCH stem cell pathways via the targeting of DKK3 and NUMB and subsequently resulting in drug resistance. Therefore, blocking this adaptive mechanism during chemotherapy may reduce the development of chemotherapy resistance and maximize the therapeutic effect.

Journal of Experimental & Clinical Cancer Research published new progress about 3′-Untranslated region Role: BSU (Biological Study, Unclassified), BIOL (Biological Study) (3′-UTR). 6823-69-4 belongs to class imidazoles-derivatives, and the molecular formula is C30H30Cl2N6O2, Reference of 6823-69-4.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Ling, Irene; Sobolev, Alexandre N.; Dalgarno, Scott J. published the artcile< Inclusion complexes of imidazolium carboxylate-metal species in the water-soluble sulfonated calix[4]arene system>, Computed Properties of 700370-07-6, the main research area is preparation imidazolium carboxylate metal water sulfonated calixarene inclusion complex; crystal structure imidazolium carboxylate metal sulfonated calixarene inclusion complex.

Two multi-component crystal structures comprising a carboxylic acid-functionalized imidazolium zwitterion, a p-sulfonatocalix[4]arene anion and aquated metal ion (Na+ or Y3+) with or without an auxiliary component (the 3-methoxyphenyl-triphenylphosphonium cation) are reported. The carboxylic acid-functionalized imidazolium ion binds either as a monodentate or a bidentate ligand depending on the nature of the metal ions, and a bi-layer arrangement prevails in the extended structure regardless of the type of metal ion employed or presence/lack of auxiliary component.

Journal of Coordination Chemistry published new progress about Crystal structure. 700370-07-6 belongs to class imidazoles-derivatives, and the molecular formula is C6H9ClN2O2, Computed Properties of 700370-07-6.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Zhu, Jinbo; Yan, Zhiqiang; Boskovic, Filip; Haynes, Cally J. E.; Kieffer, Marion; Greenfield, Jake L.; Wang, Jin; Nitschke, Jonathan R.; Keyser, Ulrich F. published the artcile< FeII4L4 tetrahedron binds and aggregates DNA Gquadruplexes>, Product Details of C5H5N5, the main research area is iron ligand tetrahedron metal organic cage DNA G quadruplex.

Since the discovery of the G-quadruplex (G4) structure in telomeres in 1980s, studies have established the role it plays in various biol. processes. Here we report binding between DNA G4 and a self-assembled tetrahedral metal-organic cage 1 and consequent formation of aggregates, whereby the cage protects the DNA G4 from cleavage by S1 nuclease. We monitor DNA-cage interaction using fluorescence spectroscopy, firstly by quenching of a fluorescent label appended to the 5′ end of G4. Secondly, we detect the decrease in fluorescence of the G4-selective dyes thioflavin-T and Zn-PPIX bound to various DNA G4 sequences following the addition of cage 1. Our results demonstrate that 1 interacts with a wide range of G4s. Moreover, gel electrophoresis, CD and dynamic light scattering measurements establish the binding of 1 to G4 and indicate the formation of aggregate structures. Finally, we find that DNA G4 contained in an aggregate of cage 1 is protected from cleavage by S1 nuclease.

Chemical Science published new progress about Absorption spectra. 452-06-2 belongs to class imidazoles-derivatives, and the molecular formula is C5H5N5, Product Details of C5H5N5.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Takenaga, Keizo; Koshikawa, Nobuko; Nagase, Hiroki published the artcile< Intercellular transfer of mitochondrial DNA carrying metastasis-enhancing pathogenic mutations from high- to low-metastatic tumor cells and stromal cells via extracellular vesicles>, Reference of 6823-69-4, the main research area is mtDNA stromal EV metastasis enhancing pathogenic mutation intercellular transfer; Extracellular vesicles; Intercellular transfer; Lung cancer; Metastasis; Mitochondria; Mitochondrial DNA; Mutation; Tumor microenvironment.

Mitochondrial DNA (mtDNA) carrying certain pathogenic mutations or single nucleotide variants (SNVs) enhances the invasion and metastasis of tumor cells, and some of these mutations are homoplasmic in tumor cells and even in tumor tissues. On the other hand, intercellular transfer of mitochondria and cellular components via extracellular vesicles (EVs) and tunneling nanotubes (TNTs) has recently attracted intense attention in terms of cell-to-cell communication in the tumor microenvironment. It remains unclear whether metastasisenhancing pathogenic mutant mtDNA in tumor cells is intercellularly transferred between tumor cells and stromal cells. In this study, we investigated whether mtDNA with the NADH dehydrogenase subunit 6 (ND6) G13997A pathogenic mutation in highly metastatic cells can be horizontally transferred to low-metastatic cells and stromal cells in the tumor microenvironment. When MitoTracker Deep Red-labeled high-metastatic Lewis lung carcinoma A11 cells carrying the ND6 G13997A mtDNA mutation were cocultured with Cell Light mitochondria-GFP-labeled low-metastatic P29 cells harboring wild-type mtDNA, bidirectional transfer of red- and green-colored vesicles, probably mitochondria-related EVs, was observed in a time-dependent manner. Similarly, intercellular transfer of mitochondria-related EVs occurred between A11 cells and α-smooth muscle actin (α-SMA)-pos. cancer-associated fibroblasts (CAFs, WA-mFib), macrophages (RAW264.7) and cytotoxic T cells (CTLL-2). Intercellular transfer was suppressed by inhibitors of EV release. The large and small EV fractions (L-EV and S-EV, resp.) prepared from the conditioned medium by differential ultracentrifugation both were found to contain mtDNA, although only S-EVs were efficiently incorporated into the cells. Several subpopulations had evidence of LC3-II and contained degenerated mitochondrial components in the S-EV fraction, signaling to the existence of autophagy-related S-EVs. Interestingly, the S-EV fraction contained a MitoTracker-pos. subpopulation, which was inhibited by the respiration inhibitor antimycin A, indicating the presence of mitochondria with membrane potential. It was also demonstrated that mtDNA was transferred into mtDNA-less ρ0 cells after coculture with the S-EV fraction. In syngeneic mouse s.c. tumors formed by a mixture of A11 and P29 cells, the mitochondria-related EVs released from A11 cells reached distantly positioned P29 cells and CAFs. These results suggest that metastasis-enhancing pathogenic mtDNA derived from metastatic tumor cells is transferred to low-metastatic tumor cells and stromal cells via S-EVs in vitro and in the tumor microenvironment, inferring a novel mechanism of enhancement of metastatic potential during tumor progression.

BMC Molecular and Cell Biology published new progress about Animal gene, ND1 Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 6823-69-4 belongs to class imidazoles-derivatives, and the molecular formula is C30H30Cl2N6O2, Reference of 6823-69-4.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Angulo, Sandra; Morales, Albert; Danese, Silvio; Llacuna, Laura; Masamunt, Maria Carme; Pultz, Nicole; Cifone, Maria Grazia; De Simone, Claudio; Delgado, Salvadora; Vila, Jordi; Panes, Julian; Donskey, Curtis; Fernandez-Checa, Jose C.; Fiocchi, Claudio; Sans, Miquel published the artcile< Probiotic sonicates selectively induce mucosal immune cells apoptosis through ceramide generation via neutral sphingomyelinase>, Application In Synthesis of 6823-69-4, the main research area is NSMase mononuclear cell apoptosis ceramide probiotic lamina propria.

Background: Probiotics appear to be beneficial in inflammatory bowel disease, but their mechanism of action is incompletely understood. We investigated whether probiotic-derived sphingomyelinase mediates this beneficial effect. Methodol./Principal Findings: Neutral sphingomyelinase (NSMase) activity was measured in sonicates of the probiotic L. brevis (LB) and S. thermophilus (ST) and the non-probiotic E. coli (EC) and E. faecalis (EF). Lamina propria mononuclear cells (LPMC) were obtained from patients with Crohn’s disease (CD) and Ulcerative Colitis (UC), and peripheral blood mononuclear cells (PBMC) from healthy volunteers, analyzing LPMC and PBMC apoptosis susceptibility, reactive oxygen species (ROS) generation and JNK activation. In some experiments, sonicates were preincubated with GSH or GW4869, a specific NSMase inhibitor. NSMase activity of LB and ST was 10-fold that of EC and EF sonicates. LB and ST sonicates induced significantly more apoptosis of CD and UC than control LPMC, whereas EC and EF sonicates failed to induce apoptosis. Pre-stimulation with anti-CD3/CD28 induced a significant and time-dependent increase in LB-induced apoptosis of LPMC and PBMC. Exposure to LB sonicates resulted in JNK activation and ROS production by LPMC. NSMase activity of LB sonicates was completely abrogated by GW4869, causing a dose-dependent reduction of LB-induced apoptosis. LB and ST selectively induced immune cell apoptosis, an effect dependent on the degree of cell activation and mediated by bacterial NSMase. Conclusions: These results suggest that induction of immune cell apoptosis is a mechanism of action of some probiotics, and that NSMase-mediated ceramide generation contributes to the therapeutic effects of probiotics.

PLoS One published new progress about Apoptosis. 6823-69-4 belongs to class imidazoles-derivatives, and the molecular formula is C30H30Cl2N6O2, Application In Synthesis of 6823-69-4.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem