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1.
J Am Chem Soc ; 2024 Aug 05.
Article de Anglais | MEDLINE | ID: mdl-39102638

RÉSUMÉ

Stereoconvergent reactions enable the transformation of mixed stereoisomers into well-defined, chiral products─a crucial strategy for handling Z/E-mixed olefins, which are common but challenging substrates in organic synthesis. Herein, we report a stereoconvergent and highly enantioselective method for synthesizing Z-homoallylic alcohols via the nickel-catalyzed reductive coupling of Z/E-mixed 1,3-dienes with aldehydes. This process is enabled by an N-heterocyclic carbene ligand characterized by C2-symmetric backbone chirality and bulky 2,6-diisopropyl N-aryl substituents. Our method achieves excellent stereocontrol over both enantioselectivity and Z-selectivity in a single step, producing chiral Z-homoallylic alcohols that are valuable in natural products and pharmaceuticals.

2.
J Cell Mol Med ; 28(13): e18510, 2024 Jul.
Article de Anglais | MEDLINE | ID: mdl-38953409

RÉSUMÉ

In recent years, inflammatory disorders have emerged as a significant concern for human health. Through ongoing research on anti-inflammatory agents, alpinetin has shown promising anti-inflammatory properties, including involvement in epigenetic modification pathways. As a crucial regulator of epigenetic modifications, Mecp2 may play a role in modulating the epigenetic effects of alpinetin, potentially impacting its anti-inflammatory properties. To test this hypothesis, two key components, p65 (a member of NF-KB family) and p300 (a type of co-activator), were screened by the expression profiling microarray, which exhibited a strong correlation with the intensity of LPS stimulation in mouse macrophages. Meanwhile, alpinetin demonstrates the anti-inflammatory properties through its ability to disrupt the synthesis of p65 and its interaction with promoters of inflammatory genes, yet it did not exhibit similar effects on p300. Additionally, Mecp2 can inhibit the binding of p300 by attaching to the methylated inflammatory gene promoter induced by alpinetin, leading to obstacles in promoter acetylation and subsequently impacting the binding of p65, ultimately enhancing the anti-inflammatory capabilities of alpinetin. Similarly, in a sepsis mouse model, it was observed that homozygotes overexpressing Mecp2 showed a greater reduction in organ damage and improved survival rates compared to heterozygotes when administered by alpinetin. However, blocking the expression of DNA methyltransferase 3A (DNMT3A) resulted in the loss of Mecp2's anti-inflammatory assistance. In conclusion, Mecp2 may augment the anti-inflammatory effects of alpinetin through epigenetic 'crosstalk', highlighting the potential efficacy of a combined therapeutic strategy involving Mecp2 and alpinetin for anti-inflammatory intervention.


Sujet(s)
Anti-inflammatoires , Épigenèse génétique , Flavanones , Protéine-2 de liaison au CpG méthylé , Régions promotrices (génétique) , Protéine-2 de liaison au CpG méthylé/métabolisme , Protéine-2 de liaison au CpG méthylé/génétique , Animaux , Flavanones/pharmacologie , Épigenèse génétique/effets des médicaments et des substances chimiques , Souris , Anti-inflammatoires/pharmacologie , Cellules RAW 264.7 , Méthylation de l'ADN/effets des médicaments et des substances chimiques , Lipopolysaccharides/pharmacologie , Facteur de transcription RelA/métabolisme , Sepsie/traitement médicamenteux , Sepsie/génétique , Sepsie/métabolisme , Macrophages/métabolisme , Macrophages/effets des médicaments et des substances chimiques , Inflammation/traitement médicamenteux , Inflammation/anatomopathologie , Inflammation/génétique , Inflammation/métabolisme , DNA methyltransferase 3A/métabolisme , Mâle , Protéine p300-E1A/métabolisme , Modèles animaux de maladie humaine , Souris de lignée C57BL , DNA (cytosine-5-)-methyltransferase/métabolisme , DNA (cytosine-5-)-methyltransferase/génétique
3.
Biodivers Data J ; 12: e126064, 2024.
Article de Anglais | MEDLINE | ID: mdl-38841137

RÉSUMÉ

Background: The protection of urban biodiversity plays a critical role in maintaining urban ecological security. As a unique taxon of urban wildlife, birds have been intensively used as an indicator of our surrounding environment. Although the diversity of urban bird species has received increasing attention, present studies are mainly focused on urban parks. As one of the important components of the urban ecosystem, the university campus also plays a critical role in maintaining bird diversity. Due to the lack of observation data, it is a challenge to evaluate the impact of the environmental conditions on campus bird diversity. Given the most concentrated higher education resources in China, Nanjing has a large number of universities, covering a wide area of the urban landscape. The landscape of these universities usually has a high percentage of green space as well as waterbodies, which is conducive to attracting various bird species to inhabit. Here, we conducted a one-year bird survey from January 2019 to December 2019 in 12 universities in Nanjing and provided an occurrence dataset containing detailed species and geographical information, providing a good source to study the ecological and anthropogenic factors on urban bird diversity on a local and larger scale. New information: This dataset represents the first annual record of birds publicly released by 12 universities in Nanjing, Jiangsu Province. It includes classification information, population, distribution and survey details. All data have been published on GBIF.

4.
J Am Chem Soc ; 146(22): 14915-14921, 2024 Jun 05.
Article de Anglais | MEDLINE | ID: mdl-38781401

RÉSUMÉ

Unactivated aliphatic alkenes are particularly desirable as starting materials because they are readily accessible in large quantities, but the enantioselective intermolecular reductive coupling of unactivated alkenes with imines is challenging. In this paper, we report a method for nickel-catalyzed intermolecular reductive coupling reactions between aliphatic alkenes and imines to yield chiral amines with excellent enantioselectivities and good linear selectivities. The reaction conditions are compatible with a broad range of aliphatic alkenes, including those derived from bioactive molecules. The success of this method can be attributed to the use of newly developed monodentate chiral spiro phosphine ligands.

5.
J Am Chem Soc ; 146(8): 5643-5649, 2024 Feb 28.
Article de Anglais | MEDLINE | ID: mdl-38327018

RÉSUMÉ

We developed a method for the enantioselective synthesis of germanium-stereogenic compounds by the desymmetric carbene insertion of dihydrogermanes. A chiral rhodium phosphate catalyst decomposes diaryldiazo-methanes to generate rhodium carbenes that insert enantioselectively into one of the two Ge-H bonds of dihydrogermanes to form germanium-stereogenic compounds under mild reaction conditions. By this method, a variety of chiral germanes with germanium-stereogenic centers were synthesized in high yields and excellent enantioselectivities. Kinetic studies of the reaction showed that the diazo decomposition process was the rate-determining step. The remaining Ge-H bond of the chiral germane products provides a possibility for preparing chiral tetra-substituted germanium-stereogenic compounds.

6.
J Am Chem Soc ; 146(5): 3458-3470, 2024 Feb 07.
Article de Anglais | MEDLINE | ID: mdl-38270100

RÉSUMÉ

Ligand modulation of transition-metal catalysts to achieve optimal reactivity and selectivity in alkene hydrofunctionalization is a fundamental challenge in synthetic organic chemistry. Hydroaminoalkylation, an atom-economical approach for alkylating amines using alkenes, is particularly significant for amine synthesis in the pharmaceutical, agrochemical, and fine chemical industries. However, the existing methods usually require specific substrate combinations to achieve precise regio- and stereoselectivity, which limits their practical utility. Protocols allowing for regiodivergent hydroaminoalkylation from the same starting materials, controlling both regiochemical and stereochemical outcomes, are currently absent. Herein, we report a ligand-controlled, regiodivergent nickel-catalyzed hydroaminoalkylation of unactivated alkenes with N-sulfonyl amines. The reaction initiates with amine dehydrogenation and involves aza-nickelacycle intermediates. Tritert-butylphosphine promotes branched regioselectivity and syn diastereoselectivity, whereas ethyldiphenylphosphine enables linear selectivity, yielding regioisomers with inverse orientation. Systematic evaluation of diverse monodentate phosphine ligands reveals distinct regioselectivity cliffs, and % Vbur (min), a ligand steric descriptor, was established as a predictive parameter correlating ligand structure to regioselectivity. Computational investigations supported experimental findings, offering mechanistic insights into the origins of regioselectivity. Our method provides an efficient and predictable route for amine synthesis, demonstrating broad substrate scope, excellent tolerance toward various functional groups, and practical advantages. These include the use of readily available starting materials and cost-effective nickel(II) salts as precatalysts.

7.
Org Lett ; 26(14): 2729-2732, 2024 Apr 12.
Article de Anglais | MEDLINE | ID: mdl-37294050

RÉSUMÉ

Highly substituted aminotetrahydropyrans were synthesized via sequential C-H functionalizations. The process was initiated with a Pd(II)-catalyzed stereoselective γ-methylene C-H arylation of aminotetrahydropyran, followed by α-alkylation or arylation of the corresponding primary amine. The initial γ-C-H (hetero)arylation was compatible with a range of aryl iodides containing various substituents and provided the corresponding products in moderate to good yields. The subsequent α-alkylation or arylation of the isolated arylated products proceeded with high diastereoselectivity to afford value-added disubstituted aminotetrahydropyrans.

8.
Histol Histopathol ; 39(1): 117-130, 2024 Jan.
Article de Anglais | MEDLINE | ID: mdl-37129345

RÉSUMÉ

Keratin 80 (KRT80) is a filament protein that participates in cell differentiation and the integrity of the epithelial barrier. Here, KRT80 expression was higher in gastric cancer compared with normal mucosa at both mRNA and protein levels by bioinformatic analysis, qRT-PCR and Western blot (p<0.05), however, the methylation of KRT80 was lower than in normal mucosa (p<0.05). There was a negative relationship between promoter methylation and expression level of KRT80 gene in gastric cancer (p<0.05). KRT80 mRNA and protein expression was positively correlated with the differentiation of gastric cancer (p<0.05), while KRT80 methylation was negatively associated with gastric cancer differentiation and p53 mutation (p<0.05). The expression of KRT80 mRNA was positively linked to the short survival time of gastric cancers (p<0.05). The differential genes of KRT80 mRNA were involved in ligand-receptor interaction, estrogen signal pathway, peptidase, filament and cytoskeleton, keratinocyte differentiation, vitamin D receptor, muscle contraction, and B cell-mediated immunity (p<0.05). KRT80-related genes were classified into cell adhesion and junction, cadherin binding, skin and epidermis development, and so forth (p<0.05). KRT80 knockdown suppressed proliferation, anti-apoptosis, anti-pyroptosis, migration, invasion and epithelial-mesenchymal transition in gastric cancer cells (p<0.05). These findings indicated that up-regulated expression of KRT80 played a crucial part in gastric carcinogenesis, and might be considered as a biological marker for aggressive behaviors and poor prognosis. Its silencing might be used as an approach of target therapy for gastric cancer patients.


Sujet(s)
Tumeurs de l'estomac , Humains , Marqueurs biologiques tumoraux/génétique , Marqueurs biologiques tumoraux/métabolisme , Différenciation cellulaire , Lignée cellulaire tumorale , Mouvement cellulaire/génétique , Prolifération cellulaire , Transition épithélio-mésenchymateuse/génétique , Régulation de l'expression des gènes tumoraux , Pronostic , ARN messager/métabolisme , Tumeurs de l'estomac/métabolisme
9.
Sci Rep ; 13(1): 20135, 2023 11 16.
Article de Anglais | MEDLINE | ID: mdl-37978247

RÉSUMÉ

Colorectal cancer (CRC) is a common and deadly cancer worldwide with a high lethality rate. Disulfidptosis has been found to be an emerging mode of death in cancer, and the purpose of this study was to explore the relationship between disulfidptosis-related lncRNAs (DRLs) and CRC and to develop a prognostic model for CRC and DRLs. The gene expression data and clinicopathologic information of colorectal cancer patients were obtained from The Cancer Genome Atlas (TCGA) and screened for DRLs based on correlation analysis. The least absolute shrinkage and selection operator (LASSO) and Cox regression were used to construct the prognostic model, and its validation was carried out by PCA and receiver operating characteristic (ROC) curves. We constructed nomograms combined with the model. Finally, the possible mechanisms by which lncRNAs affect CRC were explored by functional enrichment analysis, immune infiltration and immune escape analysis. In summary, we developed a prognostic marker consisting of lncRNAs associated with disulfidptosis to help clinicians predict the survival of different CRC patients and use different targeted therapies and immunotherapies depending on the condition.


Sujet(s)
Tumeurs colorectales , ARN long non codant , Humains , ARN long non codant/génétique , Microenvironnement tumoral/génétique , Pronostic , Nomogrammes , Tumeurs colorectales/génétique
10.
J Cell Biochem ; 124(11): 1749-1763, 2023 11.
Article de Anglais | MEDLINE | ID: mdl-37796169

RÉSUMÉ

In this study, we investigated the effects of sweroside on podocyte injury in diabetic nephropathy (DN) mice and elucidated its molecular mechanisms. We conducted in vivo experiments using a C57BL/6 mice model of DN to explore the effects of sweroside on proteinuria and podocyte injury in DN mice. In in vitro experiments, conditionally immortalized mouse podocytes were treated with high glucose and sweroside, and the protective effects of sweroside on podocyte injury were analyzed. In vitro, Akt/BAD pathways were detected using gene siRNA silencing assays and found to be involved in the protective roles of sweroside in high glucose-mediated podocyte injury. In vivo, sweroside significantly decreased albuminuria in DN mice (p < 0.01). periodic acid-Schiff staining showed that sweroside alleviated the glomerular volume and mesangium expansion in DN mice. Consistently, western blot and reverse transcription-polymerase chain reaction analyses showed that the profibrotic molecule expression in the glomeruli declined in sweroside-treated DN mice. Immunofluorescent results showed that sweroside preserved nephrin and podocin expression, and transmission electron microscopy showed that sweroside attenuated podocyte injury. In DN mice, sweroside decreased podocyte apoptosis, and increased nephrin, podocin expression and decreased desmin and HIF1α expression. These results confirmed that sweroside ameliorated albuminuria, glomerulomegaly, and glomerulosclerosis in these mice. Experiments in vitro revealed that sweroside improved HG-induced podocyte injury and apoptosis. Sweroside stimulated activation of the Akt/BAD pathway and upregulated Bcl-2-associated death promoter (BAD) and p-Akt. Overall, sweroside protected podocytes from injury and prevented the progression of DN, providing a novel strategy for the treatment of DN.


Sujet(s)
Diabète expérimental , Néphropathies diabétiques , Podocytes , Souris , Animaux , Podocytes/métabolisme , Protéines proto-oncogènes c-akt/métabolisme , Albuminurie/traitement médicamenteux , Albuminurie/métabolisme , Diabète expérimental/métabolisme , Souris de lignée C57BL , Néphropathies diabétiques/traitement médicamenteux , Néphropathies diabétiques/métabolisme , Glucose/métabolisme , Apoptose
11.
Clin. transl. oncol. (Print) ; 25(10): 3042-3056, oct. 2023. ilus, tab, graf
Article de Anglais | IBECS | ID: ibc-225084

RÉSUMÉ

Background Belonging to the G-protein coupled receptor 1 family, G protein-coupled receptor 176 (GPR176) is associated with the Gz/Gx G-protein subclass and is capable of decreasing cAMP production. Methods GPR176 expression was detected by qRT-PCR, bioinformatics analysis, Western blot and immunohistochemistry, and compared with clinicopathological characteristics of breast cancer. GPR176-related genes and pathways were subjected to bioinformatic analysis. We also explored the effects of GPR176 on the phenotypes of breast cancer cells. Results Lower expression of GPR176 mRNA was seen in breast cancer than in normal tissues, but the opposite pattern was found for its protein (p < 0.05). GPR176 mRNA was associated with female sex, low T staging, non-Her-2+ subtypes, non-mutant p53 status in breast cancer (p < 0.05). GPR176 methylation was negatively correlated with its mRNA level and T staging in breast cancer, and was higher in breast cancer than normal tissues (p < 0.05). GPR176 protein expression was positively correlated with older age, small tumor size, and non-luminal-B subtype of breast cancers (p < 0.05). The differential genes of GPR176 were involved in receptor-ligand interaction, RNA maturation, and so forth (p < 0.05). GPR176-related genes were categorized into cell mobility, membrane structure, and so on (p < 0.05). GPR176 knockdown weakened the proliferation, glucose catabolism, anti-apoptosis, anti-pyroptosis, migration, invasion, and epithelial-mesenchymal transition of breast cancer cells. Conclusion These results indicate that GPR176 might be involved in the tumorigenesis and subsequent progression of breast cancer by deteriorating aggressive phenotypes. It might be utilized as a potential biomarker to indicate the aggressive behaviors and poor prognosis of breast cancer and a potential target of genetic therapy (AU)


Sujet(s)
Humains , Femelle , Tumeurs du sein/génétique , Tumeurs du sein/métabolisme , Thérapie génétique , Régulation de l'expression des gènes tumoraux , ARN messager/génétique , Marqueurs biologiques tumoraux , Lignée cellulaire tumorale , Mouvement cellulaire , Prolifération cellulaire , Pronostic , Phénotype
12.
J Am Chem Soc ; 145(35): 19195-19201, 2023 Sep 06.
Article de Anglais | MEDLINE | ID: mdl-37616490

RÉSUMÉ

We present the first enantioselective nickel-catalyzed borylative coupling of 1,3-dienes with aldehydes, providing an efficient route to highly valuable homoallylic alcohols in a single step. The reaction involves the 1,4-carboboration of dienes, leading to the formation of C-C and C-B bonds accompanied by the construction of two continuous stereogenic centers. Enabled by a chiral spiro phosphine-oxazoline nickel complex, this transformation yields products with exceptional diastereoselectivity, E-selectivity, and enantioselectivity. The diastereoselectivity of the reaction can be controlled by employing either (Z)-1,3-dienes or (E)-1,3-dienes.

13.
BMC Genomics ; 24(1): 462, 2023 Aug 17.
Article de Anglais | MEDLINE | ID: mdl-37592233

RÉSUMÉ

BACKGROUND: Numerous studies in the past have expanded our understanding of the genetic differences of global distributed cyanobacteria that originated around billions of years ago, however, unraveling how gene gain and loss drive the genetic evolution of cyanobacterial species, and the trade-off of these evolutionary forces are still the central but poorly understood issues. RESULTS: To delineate the contribution of gene flow in mediating the hereditary differentiation and shaping the microbial evolution, a global genome-wide study of bloom-forming cyanobacterium, Microcystis aeruginosa species complex, provided robust evidence for genetic diversity, reflected by enormous variation in gene repertoire among various strains. Mathematical extrapolation showed an 'open' microbial pan-genome of M. aeruginosa species, since novel genes were predicted to be introduced after new genomes were sequenced. Identification of numerous horizontal gene transfer's signatures in genome regions of interest suggested that genome expansion via transformation and phage-mediated transduction across bacterial lineage as an evolutionary route may contribute to the differentiation of Microcystis functions (e.g., carbohydrate metabolism, amino acid metabolism, and energy metabolism). Meanwhile, the selective loss of some dispensable genes at the cost of metabolic versatility is as a mean of adaptive evolution that has the potential to increase the biological fitness. CONCLUSIONS: Now that the recruitment of novel genes was accompanied by a parallel loss of some other ones, a trade-off in gene content may drive the divergent differentiation of M. aeruginosa genomes. Our study provides a genetic framework for the evolution of M. aeruginosa species and illustrates their possible evolutionary patterns.


Sujet(s)
Bactériophages , Microcystis , Microcystis/génétique , Étude d'association pangénomique , Métabolisme énergétique , Évolution moléculaire
14.
Chem Sci ; 14(32): 8644-8650, 2023 Aug 16.
Article de Anglais | MEDLINE | ID: mdl-37592986

RÉSUMÉ

Molecules with an allylic amine motif provide access to important building blocks and versatile applications of biologically relevant chemical space. The need for diverse allylic amines requires the development of increasingly general and modular multicomponent reactions for allylic amine synthesis. Herein, we report an efficient catalytic multicomponent coupling reaction of simple alkenes, aldehydes, and amides by combining nickel catalysis and Lewis acid catalysis, thus providing a practical, environmentally friendly, and modular protocol to build architecturally complex and functionally diverse allylic amines in a single step. The method is remarkably simple, shows broad functional-group tolerance, and facilitates the synthesis of drug-like allylic amines that are not readily accessible by other methods. The utilization of accessible starting materials and inexpensive Ni(ii) salt as the alternative precatalyst offers a significant practical advantage. In addition, the practicality of the process was also demonstrated in an efficient, gram-scale preparation of the prostaglandin agonist.

15.
Sensors (Basel) ; 23(11)2023 May 30.
Article de Anglais | MEDLINE | ID: mdl-37299924

RÉSUMÉ

With the rapid growth in wireless communication and IoT technologies, Radio Frequency Identification (RFID) is applied to the Internet of Vehicles (IoV) to ensure the security of private data and the accuracy of identification and tracking. However, in traffic congestion scenarios, frequent mutual authentication increases the overall computing and communication overhead of the network. For this reason, in this work, we propose a lightweight RFID security fast authentication protocol for traffic congestion scenarios, designing an ownership transfer protocol to transfer access rights to vehicle tags in non-congestion scenarios. The edge server is used for authentication, and the elliptic curve cryptography (ECC) algorithm and the hash function are combined to ensure the security of vehicles' private data. The Scyther tool is used for the formal analysis of the proposed scheme, and this analysis shows that the proposed scheme can resist typical attacks in mobile communication of the IoV. Experimental results show that, compared to other RFID authentication protocols, the calculation and communication overheads of the tags proposed in this work are reduced by 66.35% in congested scenarios and 66.67% in non-congested scenarios, while the lowest are reduced by 32.71% and 50%, respectively. The results of this study demonstrate a significant reduction in the computational and communication overhead of tags while ensuring security.


Sujet(s)
Dispositif d'identification par radio-fréquence , Dispositif d'identification par radio-fréquence/méthodes , Sécurité informatique , Internet , Algorithmes , Communication
16.
Nat Commun ; 14(1): 3326, 2023 Jun 07.
Article de Anglais | MEDLINE | ID: mdl-37286579

RÉSUMÉ

Control of the regioselectivity of α-alkylation of carbonyl compounds is a longstanding topic of research in organic chemistry. By using stoichiometric bulky strong bases and carefully adjusting the reaction conditions, selective alkylation of unsymmetrical ketones at less-hindered α-sites has been achieved. In contrast, selective alkylation of such ketones at more-hindered α-sites remains a persistent challenge. Here we report a nickel-catalysed alkylation of unsymmetrical ketones at the more-hindered α-sites with allylic alcohols. Our results indicate that the space-constrained nickel catalyst bearing a bulky biphenyl diphosphine ligand enables the preferential alkylation of the more-substituted enolate over the less-substituted enolate and reverses the conventional regioselectivity of ketone α-alkylation. The reactions proceed under neutral conditions in the absence of additives, and water is the only byproduct. The method has a broad substrate scope and permits late-stage modification of ketone-containing natural products and bioactive compounds.

17.
Food Chem ; 424: 136264, 2023 Oct 30.
Article de Anglais | MEDLINE | ID: mdl-37207599

RÉSUMÉ

Oral intake of 1,4-naphthoquinones could be a potential risk factor for hyperuricemia and gout via activation of xanthine oxidase (XO). Herein, 1,4-naphthoquinones derived from food and food-borne pollutants were selected to investigate the structure and activity relationship (SAR) and the relative mechanism for activating XO in liver S9 fractions from humans (HLS9) and rats (RLS9). The SAR analysis showed that introduction of electron-donating substituents on the benzene ring or electron-withdrawing substituents on the quinone ring improved the XO-activating effect of 1,4-naphthoquinones. Different activation potential and kinetics behaviors were observed for activating XO by 1,4-naphthoquinones in HLS9/RLS9. Molecular docking simulation and density functional theory calculations showed a good correlation between -LogEC50 and docking free energy or HOMO-LUMO energy gap. The risk of exposure to the 1,4-naphthoquinones was evaluated and discussed. Our findings are helpful to guide diet management in clinic and avoid adverse events attributable to exposure to food-derived 1,4-naphthoquinones.


Sujet(s)
Antienzymes , Naphtoquinones , Humains , Rats , Animaux , Antienzymes/composition chimique , Simulation de docking moléculaire , Xanthine oxidase/composition chimique , Appréciation des risques , Régime alimentaire
18.
Clin Transl Oncol ; 25(10): 3042-3056, 2023 Oct.
Article de Anglais | MEDLINE | ID: mdl-37079213

RÉSUMÉ

BACKGROUND: Belonging to the G-protein coupled receptor 1 family, G protein-coupled receptor 176 (GPR176) is associated with the Gz/Gx G-protein subclass and is capable of decreasing cAMP production. METHODS: GPR176 expression was detected by qRT-PCR, bioinformatics analysis, Western blot and immunohistochemistry, and compared with clinicopathological characteristics of breast cancer. GPR176-related genes and pathways were subjected to bioinformatic analysis. We also explored the effects of GPR176 on the phenotypes of breast cancer cells. RESULTS: Lower expression of GPR176 mRNA was seen in breast cancer than in normal tissues, but the opposite pattern was found for its protein (p < 0.05). GPR176 mRNA was associated with female sex, low T staging, non-Her-2+ subtypes, non-mutant p53 status in breast cancer (p < 0.05). GPR176 methylation was negatively correlated with its mRNA level and T staging in breast cancer, and was higher in breast cancer than normal tissues (p < 0.05). GPR176 protein expression was positively correlated with older age, small tumor size, and non-luminal-B subtype of breast cancers (p < 0.05). The differential genes of GPR176 were involved in receptor-ligand interaction, RNA maturation, and so forth (p < 0.05). GPR176-related genes were categorized into cell mobility, membrane structure, and so on (p < 0.05). GPR176 knockdown weakened the proliferation, glucose catabolism, anti-apoptosis, anti-pyroptosis, migration, invasion, and epithelial-mesenchymal transition of breast cancer cells. CONCLUSION: These results indicate that GPR176 might be involved in the tumorigenesis and subsequent progression of breast cancer by deteriorating aggressive phenotypes. It might be utilized as a potential biomarker to indicate the aggressive behaviors and poor prognosis of breast cancer and a potential target of genetic therapy.


Sujet(s)
Thérapie génétique , Tumeurs , Femelle , Animaux , Marqueurs biologiques , Mouvement cellulaire/génétique , Phénotype , ARN messager/génétique , Régulation de l'expression des gènes tumoraux , Prolifération cellulaire , Lignée cellulaire tumorale , Pronostic , Tumeurs/génétique
19.
Angew Chem Int Ed Engl ; 62(24): e202304427, 2023 Jun 12.
Article de Anglais | MEDLINE | ID: mdl-37057709

RÉSUMÉ

Chiral benzylic amines are privileged motifs in pharmacologically active molecules. Intramolecular enantioselective radical C(sp3 )-H functionalization by hydrogen-atom transfer has emerged as a straightforward, powerful tool for the synthesis of chiral amines, but methods for intermolecular enantioselective C(sp3 )-H amination remain elusive. Herein, we report a cationic copper catalytic system for intermolecular enantioselective benzylic C(sp3 )-H amination with peroxide as an oxidant. This mild, straightforward method can be used to transform an array of feedstock alkylarenes and amides into chiral amines with high enantioselectivities, and it has good functional group tolerance and broad substrate scope. More importantly, it can be used to synthesize bioactive molecules, including chiral drugs. Preliminary mechanistic studies indicate that the amination reaction involves benzylic radicals generated by hydrogen-atom transfer.

20.
Brain Res Bull ; 197: 1-12, 2023 06 01.
Article de Anglais | MEDLINE | ID: mdl-36935054

RÉSUMÉ

In sleep deprivation (SD) models, ferroptosis is increased. SIRT1 alleviates cognitive impairment in SD, and SIRT1/NRF2/HO1 pathway depresses ferroptosis in different diseases. Moreover, YTHDC1 can regulate SIRT1 mRNA stability. Therefore, our study explored effects of the YTHDC1/SIRT1/NRF2/HO1 axis on neuronal damage and ferroptosis in SD. The SD mouse model was established through a modified multi-platform water environment method and a cell model of ferroptosis was constructed with Erastin, followed by gain- and loss-of-function assays. In mice, the cognitive impairment and CLOCK and BMAL1 levels in hippocampal tissues were assessed. In cells, viability was measured. In mice and cells, mitochondrial ultrastructure, the content of reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), and iron, and the expression of GPX4 and ACSL4 were detected. The potential relationships among YTHDC1, SIRT1, and NRF2 were analyzed. SD mice had downregulated YTHDC1, SIRT1, NRF2, and HO1 protein expression in hippocampal tissues and increased ferroptosis. Mechanically, SIRT1 activated the NRF2/HO1 pathway through deacetylation, and YTHDC1 increased SIRT1 mRNA stability. YTHDC1 overexpression diminished mitochondrial damage, the content of ROS, iron, and MDA, and the expression of ACSL4 while enhancing GSH contents and GPX4 expression in hippocampal tissues of SD mice and Erastin-induced HT22 cells. Additionally, YTHDC1 overexpression elevated viability in Erastin-induced HT22 cells. SIRT1 or NRF2 overexpression ameliorated Erastin-induced mitochondrial damage and ferroptosis in HT22 cells. Silencing SIRT1 abolished the impact of YTHDC1 overexpression on SD mice and Erastin-induced HT22 cells. Collectively, YTHDC1 ameliorates mitochondrial damage and ferroptosis after SD by activating the SIRT1/NRF2/HO1 pathway.


Sujet(s)
Ferroptose , Souris , Animaux , Espèces réactives de l'oxygène/métabolisme , Heme oxygenase-1/métabolisme , Sirtuine-1/métabolisme , Heme oxygenase (decyclizing)/métabolisme , Facteur-2 apparenté à NF-E2/métabolisme , Transduction du signal , Privation de sommeil , Fer/métabolisme
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