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Breast cancer is one of the threatening malignant tumors with the highest mortality and incidence rate over the world. There are a lot of breast cancer patients dying every year due to the lack of effective and safe therapeutic drugs. Therefore, it is highly necessary to develop more effective drugs to overcome breast cancer. As a glycoside derivative of apigenin, cosmosiin is characterized by low toxicity, high water solubility, and wide distribution in nature. Additionally, cosmosiin has been shown to perform anti-tumor effects in cervical cancer, hepatocellular carcinoma and melanoma. However, its pharmacological effects on breast cancer and its mechanisms are still unknown. In our study, the anti-breast cancer effect and mechanism of cosmosiin were investigated by using breast cancer models in vivo and in vitro. The results showed that cosmosiin inhibited the proliferation, migration, and adhesion of breast cancer cells in vitro and suppressed the growth of tumor in vivo through binding with AhR and inhibiting it, thus regulating the downstream CYP1A1/AMPK/mTOR and PPARγ/Wnt/ß-catenin signaling pathways. Collectively, our findings have made contribution to the development of novel drugs against breast cancer by targeting AhR and provided a new direction for the research in the field of anti-breast cancer therapy.
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Neoplasias da Mama , Proliferação de Células , Citocromo P-450 CYP1A1 , PPAR gama , Receptores de Hidrocarboneto Arílico , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , PPAR gama/metabolismo , Animais , Receptores de Hidrocarboneto Arílico/metabolismo , Camundongos , Citocromo P-450 CYP1A1/metabolismo , Citocromo P-450 CYP1A1/genética , Proliferação de Células/efeitos dos fármacos , Camundongos Nus , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Camundongos Endogâmicos BALB C , Movimento Celular/efeitos dos fármacos , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Ensaios Antitumorais Modelo de Xenoenxerto , Via de Sinalização Wnt/efeitos dos fármacosRESUMO
Context-induced retrieval of drug withdrawal memory is one of the important reasons for drug relapses. Previous studies have shown that different projection neurons in different brain regions or in the same brain region such as the basolateral amygdala (BLA) participate in context-induced retrieval of drug withdrawal memory. However, whether these different projection neurons participate in the retrieval of drug withdrawal memory with same or different molecular pathways remains a topic for research. The present results showed that (1) BLA neurons projecting to the prelimbic cortex (BLA-PrL) and BLA neurons projecting to the nucleus accumbens (BLA-NAc) participated in context-induced retrieval of morphine withdrawal memory; (2) there was an increase in the expression of Arc and pERK in BLA-NAc neurons, but not in BLA-PrL neurons during context-induced retrieval of morphine withdrawal memory; (3) pERK was the upstream molecule of Arc, whereas D1 receptor was the upstream molecule of pERK in BLA-NAc neurons during context-induced retrieval of morphine withdrawal memory; (4) D1 receptors also strengthened AMPA receptors, but not NMDA receptors, -mediated glutamatergic input to BLA-NAc neurons via pERK during context-induced retrieval of morphine withdrawal memory. These results suggest that different projection neurons of the BLA participate in the retrieval of morphine withdrawal memory with diverse molecular pathways.
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Complexo Nuclear Basolateral da Amígdala , Morfina , Neurônios , Núcleo Accumbens , Síndrome de Abstinência a Substâncias , Animais , Complexo Nuclear Basolateral da Amígdala/metabolismo , Masculino , Síndrome de Abstinência a Substâncias/metabolismo , Síndrome de Abstinência a Substâncias/fisiopatologia , Morfina/farmacologia , Neurônios/metabolismo , Núcleo Accumbens/metabolismo , Memória/fisiologia , Receptores de AMPA/metabolismo , Ratos , Dependência de Morfina/metabolismo , Tonsila do Cerebelo/metabolismo , Ratos Sprague-Dawley , Receptores de Dopamina D1/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Vias Neurais/metabolismo , Córtex Pré-Frontal/metabolismoRESUMO
BACKGROUND: Costaceae, commonly known as the spiral ginger family, consists of approximately 120 species distributed in the tropical regions of South America, Africa, and Southeast Asia, of which some species have important ornamental, medicinal and ecological values. Previous studies on the phylogenetic and taxonomic of Costaceae by using nuclear internal transcribed spacer (ITS) and chloroplast genome fragments data had low resolutions. Additionally, the structures, variations and molecular evolution of complete chloroplast genomes in Costaceae still remain unclear. Herein, a total of 13 complete chloroplast genomes of Costaceae including 8 newly sequenced and 5 from the NCBI GenBank database, representing all three distribution regions of this family, were comprehensively analyzed for comparative genomics and phylogenetic relationships. RESULT: The 13 complete chloroplast genomes of Costaceae possessed typical quadripartite structures with lengths from 166,360 to 168,966 bp, comprising a large single copy (LSC, 90,802 - 92,189 bp), a small single copy (SSC, 18,363 - 20,124 bp) and a pair of inverted repeats (IRs, 27,982 - 29,203 bp). These genomes coded 111 - 113 different genes, including 79 protein-coding genes, 4 rRNA genes and 28 - 30 tRNAs genes. The gene orders, gene contents, amino acid frequencies and codon usage within Costaceae were highly conservative, but several variations in intron loss, long repeats, simple sequence repeats (SSRs) and gene expansion on the IR/SC boundaries were also found among these 13 genomes. Comparative genomics within Costaceae identified five highly divergent regions including ndhF, ycf1-D2, ccsA-ndhD, rps15-ycf1-D2 and rpl16-exon2-rpl16-exon1. Five combined DNA regions (ycf1-D2 + ndhF, ccsA-ndhD + rps15-ycf1-D2, rps15-ycf1-D2 + rpl16-exon2-rpl16-exon1, ccsA-ndhD + rpl16-exon2-rpl16-exon1, and ccsA-ndhD + rps15-ycf1-D2 + rpl16-exon2-rpl16-exon1) could be used as potential markers for future phylogenetic analyses and species identification in Costaceae. Positive selection was found in eight protein-coding genes, including cemA, clpP, ndhA, ndhF, petB, psbD, rps12 and ycf1. Maximum likelihood and Bayesian phylogenetic trees using chloroplast genome sequences consistently revealed identical tree topologies with high supports between species of Costaceae. Three clades were divided within Costaceae, including the Asian clade, Costus clade and South American clade. Tapeinochilos was a sister of Hellenia, and Parahellenia was a sister to the cluster of Tapeinochilos + Hellenia with strong support in the Asian clade. The results of molecular dating showed that the crown age of Costaceae was about 30.5 Mya (95% HPD: 14.9 - 49.3 Mya), and then started to diverge into the Costus clade and Asian clade around 23.8 Mya (95% HPD: 10.1 - 41.5 Mya). The Asian clade diverged into Hellenia and Parahellenia at approximately 10.7 Mya (95% HPD: 3.5 - 25.1 Mya). CONCLUSION: The complete chloroplast genomes can resolve the phylogenetic relationships of Costaceae and provide new insights into genome structures, variations and evolution. The identified DNA divergent regions would be useful for species identification and phylogenetic inference in Costaceae.
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Genoma de Cloroplastos , Filogenia , Teorema de Bayes , Genômica/métodos , DNARESUMO
Chronic morphine withdrawal memory formation is a complex process influenced by various molecular mechanisms. In this study, we aimed to investigate the contributions of the basolateral amygdala (BLA) and complement component 1, q subcomponent-like 3 (C1QL3), a secreted and presynaptically targeted protein, to the formation of chronic morphine (repeat dosing of morphine) withdrawal memory using conditioned place aversion (CPA) and chemogenetic methods. We conducted experiments involving the inhibition of the BLA during naloxone-induced withdrawal to assess its impact on CPA scores, providing insights into the significance of the BLA in the chronic morphine memory formation process. We also examined changes in C1ql3/C1QL3 expression within the BLA following conditioning. Immunofluorescence analysis revealed the colocalization of C1QL3 and the G protein-coupled receptor, brain-specific angiogenesis inhibitor 3 (BAI3) in the BLA, supporting their involvement in synaptic development. Moreover, we downregulated C1QL3 expression in the BLA to investigate its role in chronic morphine withdrawal memory formation. Our findings revealed that BLA inhibition during naloxone-induced withdrawal led to a significant reduction in CPA scores, confirming the critical role of the BLA in this memory process. Additionally, the upregulation of C1ql3 expression within the BLA postconditioning suggested its participation in withdrawal memory formation. The colocalization of C1QL3 and BAI3 in the BLA further supported their involvement in synaptic development. Furthermore, downregulation of C1QL3 in the BLA effectively hindered chronic morphine withdrawal memory formation, emphasizing its pivotal role in this process. Notably, we identified postsynaptic density protein 95 (PSD95) as a potential downstream effector of C1QL3 during chronic morphine withdrawal memory formation. Blocking PSD95 led to a significant reduction in the CPA score, and it appeared that C1QL3 modulated the ubiquitination-mediated degradation of PSD95, resulting in decreased PSD95 protein levels. This study underscores the importance of the BLA, C1QL3 and PSD95 in chronic morphine withdrawal memory formation. It provides valuable insights into the underlying molecular mechanisms, emphasizing their significance in this intricate process.
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Complexo Nuclear Basolateral da Amígdala , Proteína 4 Homóloga a Disks-Large , Memória , Morfina , Síndrome de Abstinência a Substâncias , Animais , Morfina/farmacologia , Síndrome de Abstinência a Substâncias/metabolismo , Masculino , Camundongos , Memória/efeitos dos fármacos , Proteína 4 Homóloga a Disks-Large/metabolismo , Complexo Nuclear Basolateral da Amígdala/metabolismo , Complexo Nuclear Basolateral da Amígdala/efeitos dos fármacos , Complemento C1q/metabolismo , Camundongos Endogâmicos C57BL , Naloxona/farmacologiaRESUMO
MAIN CONCLUSION: This study revealed the transcriptome-wide m6A methylation profile under drought stress and found that TaETC9 might regulate drought tolerance through mediating RNA methylation in wheat. Drought is one of the most destructive environmental constraints limiting crop growth and development. N6-methyladenosine (m6A) is a prevalent and important post-transcriptional modification in various eukaryotic RNA molecules, playing the crucial role in regulating drought response in plants. However, the significance of m6A in wheat (Triticum aestivum L.), particularly its involvment in drought response, remains underexplored. In this study, we investigated the transcriptome-wide m6A profile under drought stress using parallel m6A immunoprecipitation sequencing (MeRIP-seq). Totally, 4221 m6A peaks in 3733 m6A-modified genes were obtained, of which 373 methylated peaks exhibited differential expression between the control (CK) and drought-stressed treatments. These m6A loci were significantly enriched in proximity to stop codons and within the 3'-untranslated region. Integration of MeRIP-seq and RNA-seq revealed a positive correlation between m6A methylation and mRNA abundance and the genes displaying both differential methylation and expression were obtained. Finally, qRT-PCR analyses were further performed and the results found that the m6A-binding protein (TaETC9) showed significant up-regulation, while the m6A demethylase (TaALKBH10B) was significantly down-regulated under drought stress, contributing to increased m6A levels. Furthermore, the loss-of-function mutant of TaECT9 displayed significantly higher drought sensitivity compared to the wild type, highlighting its role in regulating drought tolerance. This study reported the first wheat m6A profile associated with drought stress, laying the groundwork for unraveling the potential role of RNA methylation in drought responses and enhancing stress tolerance in wheat through epigenetic approaches.
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Adenosina , Secas , Regulação da Expressão Gênica de Plantas , Estresse Fisiológico , Transcriptoma , Triticum , Triticum/genética , Triticum/fisiologia , Metilação , Adenosina/análogos & derivados , Adenosina/metabolismo , Estresse Fisiológico/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMO
Drought is one of the major environmental constraints for wheat production world-wide. As the progenitor and genetic reservoir of common wheat, emmer wheat is considered as an invaluable gene pool for breeding drought-tolerant wheat. Combining GWAS and eGWAS analysis of 107 accessions, we identified 86 QTLs, 105 462 eQTLs as well as 68 eQTL hotspots associating with drought tolerance (DT) in emmer wheat. A complex regulatory network composed of 185 upstream regulator and 2432 downstream drought-responsive candidates was developed, of which TtOTS1 was found to play a negative effect in determining DT through affecting root development. This study sheds light on revealing the genetic basis underlying DT, which will provide the indispensable genes and germplasm resources for elite drought tolerance wheat improvement and breeding.
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Resistência à Seca , Estudo de Associação Genômica Ampla , Locos de Características Quantitativas , Triticum , Adaptação Fisiológica/genética , Resistência à Seca/genética , Regulação da Expressão Gênica de Plantas , Redes Reguladoras de Genes , Genes de Plantas , Fenótipo , Raízes de Plantas/genética , Raízes de Plantas/fisiologia , Polimorfismo de Nucleotídeo Único , Triticum/genética , Triticum/fisiologiaRESUMO
In this paper, we propose a novel and simple multi-channel broadband optical chaos generation scheme based on phase modulation and chirped fiber Bragg grating (CFBG). Firstly, phase modulation is introduced to generate more new frequency components to broaden the spectrum of the phase chaos. Meanwhile, the accumulated dispersion from CFBG distorts the intensity chaos, converts phase chaos to intensity chaos, and weakens the laser relaxation oscillation. This process would lead to energy redistribution in the power spectrum, effectively increasing the chaotic bandwidth. Then, the wavelength detuning between CFBG and the semiconductor laser is introduced to enhance the chaotic bandwidth further. The experiment results show that the 10â dB bandwidths of the five channels are up to 31.0 GHz, 34.3 GHz, 36.3 GHz, 40 GHz, and 40 GHz, respectively. Note that the maximum bandwidth of the PD in our experiment is limited to 40â GHz. In addition, the multi-channel chaotic signals obtained from the experiment system are used to generate multi-channel physical random numbers. After the post-processing operations, the total rate of five parallel high-speed physical random number generation channels is 4.64 Tbit/s (160 GSa/s × 5bit × 1 channel + 160 GSa/s × 6bit × 4 channels). As far as we know, this is the highest record of using external cavity feedback semiconductor lasers to generate random numbers, which has great potential to meet the security requirements of next-generation Tbit/s optical communication systems.
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In real-world complex systems, heterogeneous components often interact in complex connection patterns and could be schematized by a formalism of multilayer network. In this work, the synchronization characteristics of multilayer network composed of semiconductor lasers (SLs) are investigated systematically. It is demonstrated that the interplay between different layers plays an important role on the synchronization patterns. We elucidate that the performance of cluster synchronization could be facilitated effectively with the introduction of disjoint layer symmetry into network topology. Intertwined stability of clusters from different layers could be decoupled into independent, and the parameter spaces for stable synchronization are extended significantly. The robustness of our proposed regulation scheme on operation parameters is numerically evaluated. Furthermore, the generality of presented theoretical results is validated in networks with more complex topology and multiple layers.
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Quantum key distribution allows secret key generation with information theoretical security. It can be realized with photonic integrated circuits to benefit the tiny footprints and the large-scale manufacturing capacity. Continuous-variable quantum key distribution is suitable for chip-based integration due to its compatibility with mature optical communication devices. However, the quantum signal power control compatible with the mature photonic integration process faces difficulties on stability, which limits the system performance and causes the overestimation of a secret key rate that opens practical security loopholes. Here, a highly stable chip-based quantum signal power control scheme based on a biased Mach-Zehnder interferometer structure is proposed, theoretically analyzed, and experimentally implemented with standard silicon photonic techniques. Simulations and experimental results show that the proposed scheme significantly improves the system stability, where the standard deviation of the secret key rate is suppressed by an order of magnitude compared with the system using traditional designs, showing a promising and practicable way to realize a highly stable continuous-variable quantum key distribution system on chip.
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AIM: In this study, we aimed to establish a rat tooth movement model to assess miR-20's ability in enhancing the BMP2 signaling pathway and facilitate alveolar bone remodeling. METHOD: 60 male SD rats had nickel titanium spring devices placed between their left upper first molars and incisors, with the right side serving as the control. Forces were applied at varying durations (18h, 24h, 30h, 36h, 42h, 1d, 3d, 5d, 7d, 14d), and their bilateral maxillary molars and surrounding alveolar bones were retrieved for analysis. Fluorescent quantitative PCR was conducted to assess miR-20a, BMP2, Runx2, Bambi and Smad6 gene expression in alveolar bone, and western blot was performed to determine the protein levels of BMP2, Runx2, Bambi, and Smad6 after mechanical loading. RESULT: We successfully established an orthodontic tooth movement model in SD rats and revealed upregulated miR-20a expression and significantly increased BMP2 and Runx2 gene expression and protein synthesis in alveolar bone during molar tooth movement. Although Bambi and Smad6 gene expression did not significantly increase, their protein synthesis was found to decrease significantly. CONCLUSION: MiR-20a was found to be involved in rat tooth movement model alveolar bone remodeling, wherein it promoted remodeling by reducing Bambi and Smad6 protein synthesis through the BMP2 signaling pathway.
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Herein, we developed a ligand-promoted Rh(III)-catalyzed C(sp3)-H thiolation of 8-methylquinolines. The effect of ligands on improving the activity of the catalytic centers has been studied in detail and proven to be significant. Various substituents are well tolerated under this reaction condition to provide potential precursors for organic synthesis. The mechanistic study suggests that the reaction may proceed through a five-membered rhodacycle intermediate via thiolation twice.
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The detection and removal of Pb2+ is of utmost importance for environmental protection and human health due to its toxicity, persistent pollution, and bioaccumulation effects. To address the limitations associated with organic small molecule-based fluorescence probes such as poor water solubility and single functionality in detecting Pb2+, a fluorescence probe based on halloysite nanotubes was developed. This probe not only enables specific, rapid, and reliable detection of Pb2+ but also facilitates efficient removal of it from water. The development of this bifunctional fluorescent probe provides a valuable insight for designing more advanced probes targeting heavy metal ions.
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Two-dimensional (2D) materials are an excellent platform for surface-enhanced Raman spectroscopy (SERS). For ReS2, the Raman enhancement effect can be highly improved through the dipole-dipole interactions and synergistic resonance effects in the phase-engineering ReS2 films. However, the performance of the substrate can be improved further through regulating the electronic interaction between the ReS2 and probe molecules. Herein, a dynamic coulomb repulsion strategy is proposed to trigger an electronic state redistribution by asymmetric electrostatic interactions. With the phase-engineering ReS2/graphene heterostructure as a prototype, under laser excitation, the generated hot electrons in graphene and ReS2 can repel each other due to Coulomb interaction, which breaks the symmetrical distribution of hot electrons in ReS2, and increases the electronic concentration at the interface between ReS2 and the probe molecule. With R6G as the probe molecule, the asymmetric electron distribution and synergistic resonance effects on their interface improve the limit of detection to 10-12 M with an EF of 2.15 × 108. Meanwhile, the heterostructure also shows good uniformity, stability as well as unique anisotropy. This strategy can be generalized to other 2D heterostructures to obtain the ultrasensitive SERS substrates.
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Self-activated phosphors have attracted considerable attention due to their low synthesis temperature, high excitation threshold, and broad emission spectrum. And self-activated tungstate phosphors are distinguished by their low cost and stable chemical properties. Generally, it is difficult to observe luminescence from tungstate phosphors at room temperature. Furthermore, blue-emitting tungstate phosphors with high quantum efficiency are rarely reported. In this study, we succeeded in discovering high quantum-efficiency bluish-white-emitting Li2(MgxZn1-x)2W2O9 phosphors and investigating their detailed crystal structures. Upon near-ultraviolet excitation at 266 nm, these phosphors exhibit a broadband emission peak. The red shift of emission is slight with increasing Zn content in Li2(MgxZn1-x)2W2O9. A highly compact octahedral [WO6] unit is observed in the Li2(MgxZn1-x)2W2O9 phosphors. The phosphors exhibit high internal quantum efficiencies (IQEs) of 68.70% (M = Mg), 43.90% (M = Mg0.5Zn0.5), and 22.90% (M = Zn), respectively. This study provides a bluish-white-emitting tungstate phosphor with high quantum efficiency.
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BACKGROUND AND AIMS: Epidemiological evidence suggests that the phenotype of glutathione S-transferase mu 1 (GSTM1), a hepatic high-expressed phase II detoxification enzyme, is closely associated with the incidence of alcohol-related liver disease (ALD). However, whether and how hepatic GSTM1 determines the development of ALD is largely unclear. This study was designed to elucidate the role and potential mechanism(s) of hepatic GSTM1 in the pathological process of ALD. METHODS: GSTM1 was detected in the liver of various ALD mice models and cultured hepatocytes. Liver-specific GSTM1 or/and micro (miR)-743a-3p deficiency mice were generated by adenoassociated virus-8 delivered shRNA, respectively. The potential signal pathways involving in alcohol-regulated GSTM1 and GSTM1-associated ALD were explored via both genetic manipulation and pharmacological approaches. RESULTS: GSTM1 was significantly upregulated in both chronic alcohol-induced mice liver and ethanol-exposed murine primary hepatocytes. Alcohol-reduced miR-743a-3p directly contributed to the upregulation of GSTM1, since liver specific silencing miR-743a-3p enhanced GSTM1 and miR-743a-3p loss protected alcohol-induced liver dysfunctions, which was significantly blocked by GSTM1 knockdown. GSTM1 loss robustly aggravated alcohol-induced hepatic steatosis, oxidative stress, inflammation, and early fibrotic-like changes, which was associated with the activation of apoptosis signal-regulating kinase 1 (ASK1), c-Jun N-terminal kinase (JNK), and p38. GSTM1 antagonized ASK1 phosphorylation and its downstream JNK/p38 signaling pathway upon chronic alcohol consumption via binding with ASK1. ASK1 blockage significantly rescued hepatic GSTM1 loss-enhanced disorders in alcohol-fed mice liver. CONCLUSIONS: Chronic alcohol consumption-induced upregulation of GSTM1 in the liver provides a feedback protection against hepatic steatosis and liver injury by counteracting ASK1 activation. Down-regulation of miR-743a-3p improves alcohol intake-induced hepatic steatosis and liver injury via direct targeting on GSTM1. The miR-743a-3p-GSTM1 axis functions as an innate protective pathway to defend the early stage of ALD.
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Fígado Gorduroso Alcoólico , Glutationa Transferase , MicroRNAs , Animais , Camundongos , Glutationa Transferase/metabolismo , Hepatócitos/metabolismo , Hepatócitos/patologia , Fígado/patologia , MicroRNAs/metabolismo , Fígado Gorduroso Alcoólico/metabolismoRESUMO
Cytochrome P40 (CYP) enzymes dominate the metabolism of numerous endogenous and xenobiotic substances. While it is commonly believed that CYP-catalyzed reactions result in the detoxication of foreign substances, these reactions can also yield reactive intermediates that can bind to cellular macromolecules to cause cytotoxicity or irreversibly inactivate CYPs that create them.Mechanism-based inactivation (MBI) produces either irreversible or quasi-irreversible inactivation and is commonly caused by CYP metabolic bioactivation to an electrophilic reactive intermediate. Many drugs that have been known to cause MBI in CYPs have been discovered as perpetrators in drug-drug interactions throughout the last 20-30 years.This review will highlight the key findings from the recent literature about the mechanisms of CYP enzyme inhibition, with a focus on the broad mechanistic elements of MBI for widely used drugs linked to the phenomenon. There will also be a brief discussion of the clinical or pharmacokinetic consequences of CYP inactivation with regard to drug interaction and toxicity risk.Gaining knowledge about the selective inactivation of CYPs by common therapeutic drugs helps with the assessment of factors that affect the systemic clearance of co-administered drugs and improves comprehension of anticipated interactions with other drugs or xenobiotics.
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BACKGROUND: Fruquintinib is a highly selective inhibitor of vascular endothelial growth factor receptor (VEGFR). Currently, there are no reported cases of fruquintinib causing kidney-restrictive thrombotic microangiopathy (TMA) in the available Chinese and foreign literature. CASE PRESENTATION: In this case report, we presented a 73-year-old patient receiving fruquintinib for metastatic colon cancer, manifesting abundant proteinuria, in which kidney-restrictive TMA was also diagnosed through renal biopsy. As far as we were concerned, this was the frst reported in terms of fruquintinib-induced kidney-restrictive TMA confrmed by renal biopsy. CONCLUSION: This case indicates that fruquintinib may result in kidney-restrictive TMA, which is a rare but life-threatening complication of cancer treatment drug. Therefore, regular monitoring of proteinuria and blood pressure is imperative for all patients undergoing anti-VEGF drug therapy. And renal biopsy should be promptly conducted to facilitate early detection of thrombotic microangiopathy.
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Microangiopatias Trombóticas , Humanos , Microangiopatias Trombóticas/induzido quimicamente , Idoso , Masculino , Neoplasias do Colo/tratamento farmacológico , Quinazolinas/efeitos adversos , Quinazolinas/uso terapêuticoRESUMO
BACKGROUND: Kawasaki disease (KD) is a pyretic ailment predominantly observed in children aged below 5 years. There is currently a dearth of precise markers for timely identification of incomplete Kawasaki disease (IKD). It is imperative to develop updated, comprehensive, and evidence-based guidelines to effectively direct clinical practice. METHODS: The guideline development group comprised individuals with diverse expertise in both content and methodology and carried out an extensive exploration of the following digital repositories: CNKI, VIP, Wanfang Data, UpToDate, BMJ, Clinical Evidence, National Guideline Clearinghouse, Joanna Briggs Institute Library, Cochrane Library, and PubMed. The entire period from the establishment of these databases until January 1, 2024 was covered. To evaluate IKD, systematic reviews and randomised controlled trials were assessed using the risk of prejudice instrument specified in the Cochrane Handbook, along with the evidence robustness framework established by the GRADE group. The recommendations were formulated based on the findings, considering the evidence strength. After several iterations of expert consensus, the relevant professional committees in China endorsed the ultimate guideline. RESULTS: These guidelines address clinical questions regarding the classification and definition of KD, diagnosis of IKD, treatment during the acute phase of IKD, and follow-up of IKD. CONCLUSIONS: To provide healthcare professionals with guidance and decision-making bases for the diagnosis and treatment of IKD in China, 13 recommendations were formulated based on expert consensus and evidence of best practices.
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Síndrome de Linfonodos Mucocutâneos , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Síndrome de Linfonodos Mucocutâneos/terapia , Humanos , China , Pré-Escolar , Criança , LactenteRESUMO
CYP-14 members of the Caenorhabditis elegans (C. elegans) Cytochrome P450 (CYP) enzyme family, plays important roles in mitochondrial dysfunction, detoxification, lipid metabolism, defense and lifespan regulation. The review identifies CYP-14 members: cyp-14A1, cyp-14A2, cyp-14A3, cyp-14A4, cyp-14A5 and their homology with human CYP families. Despite limited studies on C. elegans cyp-14 members, the findings unraveled their complex crosstalk between mitochondrial stress, detoxification mechanisms, and lifespan regulation, emphasizing the complexity of these interconnected pathways as well as how their regulation depends on environmental cues changes including pH, nutrients, ROS and chemical stressors. The review underscores the translational relevance to human health, shedding light on potential human homologues and their implications in age-related, metabolic and respiratory diseases. Among other genes, cyp-14A2 and cyp-14A4 predominate the mitochondrial function, heat resistance, lipid metabolism, detoxification and lifespan pathways. In conclusion, these insights pave the way for future research, offering promising avenues for therapeutic interventions targeting CYP-14 activity to address age-related diseases and promote healthy aging.
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PURPOSE: Mucosal inflammation is a key feature of ulcerative colitis (UC), a chronic relapsing and remitting form of inflammatory bowel disease. Omentin-1, a newly discovered adipokine, is reported to have anti-inflammatory effects and has been found to be decreased in patients with inflammatory bowel disease. The aim of our study was to investigate the association between serum omentin-1 levels and mucosal disease activity in patients with UC. STUDY DESIGN: A total of 126 patients with UC and 77 healthy volunteers were enrolled in the study. Serum omentin-1 expression levels were measured using enzyme-linked immunosorbent assay to evaluate its potential for monitoring disease activity, including clinical and endoscopic activity. RESULTS: Serum omentin-1 levels were significantly lower in patients with UC compared to healthy controls (HC) (UC, 61.7 interquartile range: 51.5-72.6 versus healthy controls, 103.5 interquartile range: 48.3-156.2 ng/ml; P < .001). Furthermore, serum omentin-1 levels were associated with both clinical and endoscopic activity in patients with UC. Notably, omentin-1 levels were significantly lower in patients who achieved mucosal healing. Receiver operating characteristic curves indicated that serum omentin-1 levels could potentially serve as an activity index for evaluating UC. CONCLUSIONS: These findings provide further insight into the association between omentin-1 and UC, suggesting that omentin-1 may be a useful biomarker for monitoring mucosal disease activity in patients with UC.