Month: October 2022

Li, Xiang; Chen, Zhipeng; Ni, Yaojun; Bian, Chengyu; Huang, Jingjing; Chen, Liang; Xie, Xueying; Wang, Jun published the artcile< Tumor-associated macrophages secret exosomal miR-155 and miR-196a-5p to promote metastasis of non-small-cell lung cancer>, Name: p-Benzenediacrylanilide, 4′,4′′-di-2-imidazolin-2-yl-, dihydrochloride, the main research area is tumor associated macrophage mir155 transcriptome lung cancer metastasis; Tumor-associated macrophages (TAMs); epithelial-mesenchymal transition (EMT); exosomes; miR-155; miR-196a-5p; non-small-cell lung cancer (NSCLC).

Understanding the mol. basis underlying metastasis of non-small cell lung cancer (NSCLC) may provide a new therapeutic modality for the treatment of NSCLC. However, the mechanisms by which tumor-associated macrophages (TAMs) affect NSCLC metastasis remain undefined. In this study, we aimed to discover a novel regulatory pathway involved in NSCLC metastasis. Cell Counting Kit-8 (CCK-8), Transwell, western blot assays were used to assess cell viability, migration, invasion and epithelial-mesenchymal transition (EMT). Exosomes from macrophages medium were characterized, and in vitro cell coculture was further conducted to investigate M2 derived exosomes mediated crosstalk between TAMs and tumor cells. Besides, miRNA microarray was used to analyze miRNA expression profiles of M0 and M2 derived exosomes. Luciferase reporter assay was used to verify the potential binding between miRNA and mRNA. Moreover, 6-wk-old male BALB/c nude mice were performed to establish transplantation tumor model using tail vein injection. Hematoxylin & eosin staining was used to detect the metastasis of tumor tissues. We found that M2 TAMs were the main TAMs in metastatic tissues of NSCLC patients and exosomes derived from M2 TAMs were able to promote cell viability, cell migration, cell invasion and EMT in NSCLC. We demonstrated that miR-155 and miR-196a-5p were abundant in M2 TAMs and exosomes secreted by M2 TAMs. Functional experiments demonstrated that the deletion of miR-155 and miR-196a-5p in M2 TAMs significantly prevented NSCLC metastasis in vitro and in vivo. To clarify the mechanism governing miR-155 and miR-196a-5p from M2 TAMs, we carried out bioinformatics anal. to predict potential target genes. Mechanistically, miR-155 and miR-196a-5p directly bound to the 3′-UTR of Ras association domain family member 4 (RASSF4), and neg. regulating RASSF4 expression. At last, rescue assays demonstrated that miR-155 and miR-196a-5p exerted its performance by RASSF4. Overall, we revealed a new regulatory pathway that was M2 TAMs secreted exosomal miR-155 and miR-196a-5p to promote NSCLC metastasis. This dynamic and reciprocal cross-talk between NSCLC and macrophages innovatively provided a potential opportunity for diagnosis and treatment of NSCLC.

Translational Lung Cancer Research published new progress about Animal gene Role: BSU (Biological Study, Unclassified), PRP (Properties), BIOL (Biological Study) (BCAT1). 6823-69-4 belongs to class imidazoles-derivatives, and the molecular formula is C30H30Cl2N6O2, Name: p-Benzenediacrylanilide, 4′,4′′-di-2-imidazolin-2-yl-, dihydrochloride.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

D’Souza, Sara; Miller, Justin E.; Ahn, Jenny; Subandi, Raechel; Lozano, Daniel; Ramirez, James; Goff, Marisa; Davidian, Christina; Miller, Jeffrey H. published the artcile< The antibiotic trimethoprim displays strong mutagenic synergy with 2-aminopurine>, Name: 7H-Purin-2-amine, the main research area is antibiotic; mutagenesis; synergy; trimethoprim.

We show that trimethoprim (TMP), an antibiotic in current use, displays a strong synergistic effect on mutagenesis in Escherichia coli when paired with the base analog 2-aminopurine (2AP), resulting in a 35-fold increase in mutation frequencies in the rpoB-Rifr system. Combination therapies are often employed both as antibiotic treatments and in cancer chemotherapy. However, mutagenic effects of these combinations are rarely examined An anal. of the mutational spectra of TMP, 2AP, and their combination indicates that together they trigger a response via an alteration in deoxynucleoside triphosphate (dNTP) ratios that neither compound alone can trigger. A similar, although less strong, response is seen with the frameshift mutagen ICR191 and 2AP. These results underscore the need for testing the effects on mutagenesis of combinations of antibiotics and chemotherapeutics.

Antimicrobial Agents and Chemotherapy published new progress about 452-06-2. 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

Boehnke, Hendrik; Roettger, Katharina; Ingle, Rebecca A.; Marroux, Hugo J. B.; Bohnsack, Mats; Schwalb, Nina K.; Orr-Ewing, Andrew J.; Temps, Friedrich published the artcile< Electronic Relaxation Dynamics of UV-Photoexcited 2-Aminopurine-Thymine Base Pairs in Watson-Crick and Hoogsteen Conformations>, Electric Literature of 452-06-2, the main research area is electronic relaxation dynamics UV photoexcited aminopurine thymine base conformation.

The fluorescent analog 2-aminopurine (2AP) of the canonical nucleobase adenine (6-aminopurine) base-pairs with thymine (T) without disrupting the helical structure of DNA. It therefore finds frequent use in mol. biol. for probing DNA and RNA structures and conformational dynamics. However, detailed understanding of the processes responsible for fluorescence quenching remains largely elusive on a fundamental level. Although attempts have been made to ascribe decreased excited-state lifetimes to intrastrand charge-transfer and stacking interactions, possible influences from dynamic interstrand H-bonding have been widely ignored. Here, we investigate the electronic relaxation of UV-excited 2AP·T in Watson-Crick (WC) and Hoogsteen (HS) conformations. Although the WC conformation features slowed-down, monomer-like electronic relaxation in τ ∼ 1.6 ns toward ground-state recovery and triplet formation, the dynamics associated with 2AP·T in the HS motif exhibit faster deactivation in τ ∼ 70 ps. As recent research has revealed abundant transient interstrand H-bonding in the Hoogsteen motif for duplex DNA, the established model for dynamic fluorescence quenching may need to be revised in the light of our results. The underlying supramol. photophys. mechanisms are discussed in terms of a proposed excited-state double-proton transfer as an efficient deactivation channel for recovery of the HS species in the electronic ground state.

Journal of Physical Chemistry B published new progress about Double-stranded DNA Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 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

Ambati, Srinivasa Rao; Patel, Jeevan Lal; Chandrakar, Komal; Sarkar, Uttam; Penta, Santhosh; Banerjee, Subhash; Varma, Rajender S. published the artcile< One-pot, three-component synthesis of novel coumarinyl-pyrazolo[3,4-b]pyridine-3-carboxylate derivatives using [AcMIm]FeCl4 as recyclable catalyst>, Application of C6H9ClN2O2, the main research area is benzylhydrazine cyano hydroxyacrylate coumarinyl acrylaldehyde ionic liquid multicomponent reaction; benzyl coumarinyl pyrazolopyridine carboxylate preparation green chem.

Multicomponent synthesis of novel coumarin-based fused pyrazolo[3,4-b]pyridine-3-carboxylate derivatives I [R = H, OH, F, CN; R1 = Me, Et, i-Pr, t-Bu; R2 = H, MeO, Br] was developed using acidic ionic liquid, 1-acyl-3-methylimidazolium tetrachloroferrate ([AcMIm]FeCl4) under mild and environmentally benign reaction conditions. The prepared [AcMIm]FeCl4 served as a catalyst as well as the reaction medium and was reused for at least four times without significant loss of yield. The ensuing compounds, I were identified by FT-IR, 1H NMR and 13C NMR and mass spectroscopic studies. The developed method offers several advantages such as a simple protocol, excellent yields of the products (90-92%), shorter reaction time (2 h), recyclability of the catalyst, eco-friendly reaction conditions and better values of green chem. metrics like low E factor (0.32), high reaction mass efficiency (75.28%), low process mass efficiency (1.32) and high atom economy (81.82).

Journal of Molecular Structure published new progress about Aliphatic acids, esters Role: SPN (Synthetic Preparation), PREP (Preparation). 700370-07-6 belongs to class imidazoles-derivatives, and the molecular formula is C6H9ClN2O2, Application of C6H9ClN2O2.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Liu, Anqi; Jin, Shanshan; Fu, Cuicui; Cui, Shengji; Zhang, Ting; Zhu, Lisha; Wang, Yu; Shen, Steve G. F.; Jiang, Nan; Liu, Yan published the artcile< Macrophage-derived small extracellular vesicles promote biomimetic mineralized collagen-mediated endogenous bone regeneration>, Synthetic Route of 6823-69-4, the main research area is macrophage derived small extracellular vesicle mineralized collagen bone regeneration.

Macrophages play an important role in material-related immune responses and bone formation, but the functionality of macrophage-derived extracellular vesicles (EVs) in material-mediated bone regeneration is still unclear. Here, we evaluated intracellular communication through small extracellular vesicles (sEVs) and its effects on endogenous bone regeneration mediated by biomimetic intrafibrillarly mineralized collagen (IMC). After implantation in the bone defect area, IMC generated more neobone and recruited more mesenchymal stem cells (MSCs) than did extrafibrillarly mineralized collagen (EMC). More CD63+CD90+ and CD63+CD163+ cells were detected in the defect area in the IMC group than in the EMC group. To determine the functional roles of sEVs, extracellular vesicles from macrophages cultured on different mineralized collagen were isolated, and they showed no morphol. differences. However, macrophage-derived sEVs in the IMC group showed an enhanced Young’s modulus and exerted beneficial effects on the osteogenic differentiation of bone marrow MSCs by increasing the expression of the osteoblastic differentiation markers BMP2, BGLAP, COL1, and OSX and calcium nodule formation. Mechanistically, sEVs from IMC-treated macrophages facilitated MSC osteogenesis through the BMP2/Smad5 pathway, and blocking sEV secretion with GW4869 significantly impaired MSC proliferative, immunomodulative and osteogenic potential. Taken together, these findings show that macrophage-derived sEVs may serve as an emerging functional tool in biomaterial-mediated endogenous bone regeneration.

International Journal of Oral Science published new progress about Animal gene, COL1A1 Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 6823-69-4 belongs to class imidazoles-derivatives, and the molecular formula is C30H30Cl2N6O2, Synthetic Route of 6823-69-4.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Wang, Hongbin; Wei, Hong; Wang, Jingsong; Li, Lin; Chen, Anyue; Li, Zhigao published the artcile< MicroRNA-181d-5p-Containing Exosomes Derived from CAFs Promote EMT by Regulating CDX2/HOXA5 in Breast Cancer>, Safety of p-Benzenediacrylanilide, 4′,4′′-di-2-imidazolin-2-yl-, dihydrochloride, the main research area is gene expression CDX2 miR181d5p epithelial mesenchymal transition breast cancer; CDX2; HOXA5; breast cancer; cancer-associated fibroblasts; epithelial-mesenchymal transition; exosome; microRNA-181d-5p.

Recently, novel mechanisms underlying the pro-tumorigenic effects of cancer-associated fibroblasts (CAFs) have been identified in several cancers, including breast cancer. CAFs can secrete exosomes that are loaded with proteins, lipids, and RNAs to affect tumor microenvironment. Herein, we identify CAF-derived exosomes that can transfer miR-181d-5p to enhance the aggressiveness of breast cancer. Cancerous tissues and matched paracancerous tissues were surgically resected from 122 patients with breast cancer. Chromatin immunoprecipitation (ChIP) and dual luciferase reporter assays were employed to identify interaction between homeobox A5 (HOXA5) and caudal-related homeobox 2 (CDX2), as well as between CDX2 and miR-181d-5p, resp. Human breast cancer Michigan Cancer Foundation-7 (MCF-7) cells were cocultured with CAF-derived exosomes. 5-Ethynyl-2′-deoxyuridine (EdU) assay, TUNEL staining, Transwell invasion assays, and scratch tests were carried out to evaluate MCF-7 cell functions. Nude mice bearing xenografted MCF-7 cells were injected with CAF-derived exosomes, and the tumor formation was evaluated. HOXA5 expressed at a poor level in breast cancer tissues, and its overexpression retarded MCF-7 cell proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT) and facilitated its apoptosis in vitro. miR-181d-5p targets CDX2, a transcription factor binding to HOXA5 promoter. Coculture of CAFs and MCF-7 cells showed that CAFs prolonged proliferation and antagonized apoptosis of MCF-7 cells via release of exosomes. Coculture of MCF-7 cells and exosomes derived from CAFs identified miR-181d-5p as a mediator of the exosomal effects on MCF-7 cells, in part, via downregulation of CDX2 and HOXA5. CAF-derived exosomes containing miR-181d-5p promoted the tumor growth of nude mice bearing xenografted MCF-7 cells. In conclusion, exosomal miR-181d-5p plays a key role in CAF-mediated effects on tumor environment in breast cancer, likely via CDX2 and HOXA5.

Molecular Therapy–Nucleic Acids published new progress about Antigens, Thy-1 Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 6823-69-4 belongs to class imidazoles-derivatives, and the molecular formula is C30H30Cl2N6O2, Safety of p-Benzenediacrylanilide, 4′,4′′-di-2-imidazolin-2-yl-, dihydrochloride.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Milner, Phillip J.; Yang, Yang; Buchwald, Stephen L. published the artcile< In-Depth Assessment of the Palladium-Catalyzed Fluorination of Five-Membered Heteroaryl Bromides [Erratum to document cited in CA163:458639]>, Product Details of C4H5BrN2, the main research area is erratum palladium catalyzed fluorination five membered heteroaryl bromide; bromoazole palladium catalyzed fluorination theor erratum.

An updated reference 15a is provided.

Organometallics published new progress about Crystal structure. 1003-21-0 belongs to class imidazoles-derivatives, and the molecular formula is C4H5BrN2, Product Details of C4H5BrN2.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Ilgu, Muslum; Yan, Shuting; Khounlo, Ryan M.; Lamm, Monica H.; Nilsen-Hamilton, Marit published the artcile< Common secondary and tertiary structural features of aptamer-ligand interaction shared by RNA aptamers with different primary sequences>, COA of Formula: C5H5N5, the main research area is secondary tertiary structural feature RNA aptamer ligand interaction; 2-aminopurine (2AP), molecular dynamics; aminoglycoside; isothermal titration calorimetry; neomycin-B RNA aptamer.

Aptamer selection can yield many oligonucleotides with different sequences and affinities for the target mol. Here, we have combined computational and exptl. approaches to understand if aptamers with different sequences but the same mol. target share structural and dynamical features. NEO1A, with a known NMR-solved structure, displays a flexible loop that interacts differently with individual aminoglycosides, its ligand affinities and specificities are responsive to ionic strength, and it possesses an adenosine in the loop that is critical for high-affinity ligand binding. NEO2A was obtained from the same selection and, although they are only 43% identical in overall sequence, NEO1A and NEO2A share similar loop sequences. Exptl. anal. by 1D NMR and 2-aminopurine reporters combined with mol. dynamics modeling revealed similar structural and dynamical characteristics in both aptamers. These results are consistent with the hypothesis that the target ligand drives aptamer structure and also selects relevant dynamical characteristics for high-affinity aptamer-ligand interaction. Furthermore, they suggest that it might be possible to “”migrate”” structural and dynamical features between aptamer group members with different primary sequences but with the same target ligand.

Molecules published new progress about Affinity. 452-06-2 belongs to class imidazoles-derivatives, and the molecular formula is C5H5N5, COA of Formula: C5H5N5.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Choezom, Dolma; Gross, Julia Christina published the artcile< Neutral sphingomyelinase 2 controls exosome secretion by counteracting V-ATPase-mediated endosome acidification>, Application In Synthesis of 6823-69-4, the main research area is SMPD3 extracellular vesicle V ATPase maturation; Endosomal cargo sorting; Endosomal maturation; Intraluminal vesicles; Secretory multivesicular bodies; Small extracellular vesicles.

During endosome maturation, neutral sphingomyelinase 2 (nSMase2, encoded by SMPD3) is involved in budding of intraluminal vesicles (ILVs) into late endosomes or multivesicular bodies (MVBs). Fusion of these with the plasma membrane results in secretion of exosomes or small extracellular vesicles (sEVs). Here, we report that nSMase2 activity controls sEV secretion through modulation of vacuolar H+-ATPase (V-ATPase) activity. Specifically, we show that nSMase2 inhibition induces V-ATPase complex assembly that drives MVB lumen acidification and consequently reduces sEV secretion. Conversely, we further demonstrate that stimulating nSMase2 activity with the inflammatory cytokine TNFα (also known as TNF) decreases acidification and increases sEV secretion. Thus, we find that nSMase2 activity affects MVB membrane lipid composition to counteract V-ATPase-mediated endosome acidification, thereby shifting MVB fate towards sEV secretion.

Journal of Cell Science published new progress about CD81 antigens Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 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