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Coilia nasus, a migratory fish species found in the middle and lower reaches of the Yangtze River and along offshore areas of China, possesses considerable aquacultural and economic potential. However, the species faces challenges due to significant variation in the gonadal development rate among females, resulting in inconsistent ovarian maturation times at the population level, an extended reproductive period, and limitations on fish growth rate due to ovarian prematurity. In the present study, we combined genome-wide association study (GWAS) and comparative transcriptome analysis to investigate the potential single nucleotide polymorphisms (SNPs) and candidate genes associated with population-asynchronous ovarian development in C. nasus. Genotyping of the female population based on whole-genome resequencing yielded 2â¯120â¯695 high-quality SNPs, 39 of which were suggestively associated with ovarian development. Of note, a significant SNP peak on LG21 containing 30 suggestively associated SNPs was identified, with cpne5a determined as the causal gene of the peak. Therefore, single-marker and haplotype association analyses were performed on cpne5a, revealing four genetic markers ( P<0.05) and seven haplotypes (r 2>0.9) significantly associated with the phenotype. Comparative transcriptome analysis of precociously and normally maturing individuals screened out 29 and 426 overlapping differentially expressed genes in the brain and ovary, respectively, between individuals of different body sizes. Integrating the GWAS and transcriptome analysis results, this study identified genes and pathways related to hypothalamic-pituitary-gonadal axis hormone secretion, extracellular matrix, angiogenesis, and gap junctions involved in population-asynchronous ovarian development. The insights gained from this study provide a basis for a deeper understanding of the molecular mechanisms underlying ovarian development in fish and may facilitate the genetic breeding of C. nasus strains exhibiting population-synchronous ovarian development in the future.
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Estudio de Asociación del Genoma Completo , Ovario , Polimorfismo de Nucleótido Simple , Animales , Femenino , Ovario/crecimiento & desarrollo , Ovario/metabolismo , Perfilación de la Expresión Génica , Transcriptoma , Marcadores Genéticos , Peces/genética , Peces/crecimiento & desarrolloRESUMEN
Cervical cancer is one of the most leading causes of cancer death worldwide, and ferroptosis is implicated in the progression of cervical cancer. Cornichon family AMPA receptor auxiliary protein 4 (CNIH4) is involved in the progression of various human cancers; however, its function in cervical cancer remains unclear. The present study aims to investigate the role and mechanism of CNIH4 in cervical cancer using gain- and loss-of-function studies in vitro. SiHa and CaSki cells were infected with lentiviral vectors to manipulate the expression of CNIH4 in vitro, and cell viability, migration, invasion as well as ferroptosis were evaluated. Transcriptome sequencing analysis was performed to further validate the mechanism through which CNIH4 regulated the progression of cervical cancer. The expression of CNIH4 was upregulated in human cervical cancer tissues and cells, and strongly correlated with the decreases in overall survival and disease free survival rates of cervical cancer patients. CNIH4 silence inhibited, while CNIH4 overexpression facilitated the survival of human cervical cancer cells. Mechanistically, CNIH4 elevated solute carrier family 7 member 11 (SLC7A11)-mediated cystine import, and subsequently increased intracellular glutathione synthesis and glutathione peroxidase 4 activity, thereby inhibiting ferroptosis of human cervical cancer cells. SLC7A11 silence significantly abolished CNIH4-mediated inhibition of ferroptosis in cervical cancer cells in vitro. Our study for the first time reveals that CNIH4 inhibits ferroptosis of human cervical cancer cells through upregulating SLC7A11, defining CNIH4 as an attractive therapeutic and prognostic target for cervical cancer.
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Interleukin-1ß (IL-1ß)-induced signaling is one of the most important pathways in regulating inflammation and immunity. The assembly of the receptor complex, consisting of the ligand IL-1ß, the IL-1 receptor (IL-1R) type 1 (IL1R1), and the IL-1R accessory protein (IL1RAP), initiates this signaling. However, how the IL1R1-associated complex is regulated remains elusive. Angiopoietin like 3 (ANGPTL3), a key inhibitor of plasma triglyceride clearance, is mainly expressed in the liver and exists in both intracellular and extracellular secreted forms. Presently, ANGPTL3 has emerged as a highly promising drug target for hypertriglyceridemia and associated cardiovascular diseases. However, most studies have focused on the secreted form of ANGPTL3, while its intracellular role is still largely unknown. Here, we report that intracellular ANGPTL3 acts as a negative regulator of IL-1ß-triggered signaling. Overexpression of ANGPTL3 inhibited IL-1ß-induced NF-κB activation and the transcription of inflammatory genes in HepG2, THP1, and HEK293T cells, while knockdown or knockout of ANGPTL3 resulted in opposite effects. Mechanistically, ANGPTL3 interacted with IL1R1 and IL1RAP through its intracellular C-terminal fibrinogen-like domain (FLD) and disrupted the assembly of the IL1R1-associated complex. Taken together, our study reveals a novel role for ANGPTL3 in inflammation, whereby it inhibits the physiological interaction between IL1R1 and IL1RAP to maintain immune tolerance and homeostasis in the liver.
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Bacterial or viral infections, such as Brucella, mumps virus, herpes simplex virus, and Zika virus, destroy immune homeostasis of the testes, leading to spermatogenesis disorder and infertility. Of note, recent research shows that SARS-CoV-2 can infect male gonads and destroy Sertoli and Leydig cells, leading to male reproductive dysfunction. Due to the many side effects associated with antibiotic therapy, finding alternative treatments for inflammatory injury remains critical. Here, we found that Dmrt1 plays an important role in regulating testicular immune homeostasis. Knockdown of Dmrt1 in male mice inhibited spermatogenesis with a broad inflammatory response in seminiferous tubules and led to the loss of spermatogenic epithelial cells. Chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-seq) revealed that Dmrt1 positively regulated the expression of Spry1, an inhibitory protein of the receptor tyrosine kinase (RTK) signaling pathway. Furthermore, immunoprecipitation-mass spectrometry (IP-MS) and co-immunoprecipitation (Co-IP) analysis indicated that SPRY1 binds to nuclear factor kappa B1 (NF-κB1) to prevent nuclear translocation of p65, inhibit activation of NF-κB signaling, prevent excessive inflammatory reaction in the testis, and protect the integrity of the blood-testis barrier. In view of this newly identified Dmrt1- Spry1-NF-κB axis mechanism in the regulation of testicular immune homeostasis, our study opens new avenues for the prevention and treatment of male reproductive diseases in humans and livestock.
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Fertilidad , Homeostasis , FN-kappa B , Testículo , FN-kappa B/metabolismo , Fertilidad/genética , Fertilidad/inmunología , Humanos , Masculino , Testículo/inmunología , Testículo/metabolismo , Homeostasis/inmunología , Animales , Ratones , Células HEK293 , Espermatogénesis , Inflamación , Regiones Promotoras Genéticas/genética , Activación Transcripcional , Técnicas de Silenciamiento del GenRESUMEN
Fangwen Jiuwei Decoction is a traditional Chinese medicine preparation for the treatment of pneumonia developed by Shenzhen Bao'an Chinese Medicine Hospital, which shows remarkable clinical responses. Qualitative and quantitative analyses of the main active compounds are crucial for the quality control of traditional Chinese medicine prescription in clinical application. In this study, we identified nine active compounds essential for the pharmacological effects of Fangwen Jiuwei Decoction based on the analysis of the Network Pharmacology and relevant literature. Moreover, these compounds can interact with several crucial drug targets in pneumonia based on molecular docking. We applied high-performance liquid chromatography-tandem mass spectrometry method was established these nine active ingredients' qualitative and quantitative detections. The possible cleavage pathways of nine active components were determined based on secondary ions mass spectrometry. The results of high-performance liquid chromatography-tandem mass spectrometry were further validated, which show a satisfactory correlation coefficient (r > 0.99), recovery rate (≥93.31%), repeatability rate (≤5.62%), stability (≤7.95%), intra-day precision (≤6.68%), and inter-day precision (≤9.78%). The limit of detection was as low as 0.01 ng/ml. In this study, we established a high-performance liquid chromatography-tandem mass spectrometry method to qualitatively and quantitatively analyze the chemical components in the Fangwen Jiuwei Decoction extract.
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Medicamentos Herbarios Chinos , Medicamentos Herbarios Chinos/análisis , Espectrometría de Masas en Tándem/métodos , Simulación del Acoplamiento Molecular , Medicina Tradicional China , Cromatografía Líquida de Alta Presión/métodosRESUMEN
Objective To investigate the effect of glucocorticoids on the prognosis and inflammatory markers of patients with acute severe pancreatitis(SAP).Methods A retrospective collection was performed for SAP patients diagnosed and treated in the Department of General Hepatobiliary Surgery,the Second Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine from January 2020 to January 2023.SAP patients were divided into GC group and non-GC(NGC)group according to whether they used glucocorticoids(GC)or not.The two groups were compared with general data,inflammatory markers[neutrophil-lymphocyte ratio(NLR),monocyte-lymphocyte ratio(MLR),platelet-lymphocyte ratio(PLR),systemic inflammatory index(SII)and C-reactive protein-albumin ratio(CAR)],clinical events[continuous renal replacement therapy(CRRT),vasoactive drugs,ICU stay,total length of stay and survival)],and complications(organ failure,electrolyte imbalances,gastrointestinal bleeding and infection).Kaplan-Meier curve analysis of the relationship between GC and death in SAP patients.Logistic regression was used to explore the relationship between GC and death and organ failure.Results A total of 84 patients with SAP,40 in the GC group and 44 in the NGC group were included in the study.After treatment,NLR,MLR,PLR,SII and CAR in the GC group were significantly lower than those in the NGC group(P<0.05).There were no statistically significant differences between the GC and NGC groups in CRRT treatment,vasoactive drug use,surgery,ICU stay,total length of stay,electrolyte imbalance,gastrointestinal bleeding,pancreatic pseudocyst,abscess formation,pancreatic encephalopathy,and infectious complications(P>0.05);The mortality rate and organ failure incidence of patients in the GC group were significantly lower than those in the NGC group(P<0.05).The results of multivariate regression showed that the use of GC was an independent protective factor for death[OR=0.243,95% CI(0.062,0.948),P=0.042]and organ failure[OR=0.401,95% CI(0.165,0.976),P=0.044]in SAP patients.Conclusion GC can reduce the mortality rate and organ failure rate of SAP patients without increasing the incidence of additional complications,and has a high safety profile.
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Intermuscular bones (IBs) are mineralized spicules, present in the myosepta of many, but not all, teleost species. IBs are often small and sharp, and they consequently limit how the fish can be processed; the IBs may cause injury or trauma if lodged in consumers' throats or mouths, and therefore affect the appeal of the fish to many consumers. The development of IBs in teleosts is still not fully understood and the molecular basis of IB development remains to be established. Here, the characteristics of IB tissue are evaluated based on single-cell transcriptomics in wild-type zebrafish. The analysis defined 18 distinct cell types. Differentiation trajectories showed that IBs are derived from tendons and that a core tendon-osteoblast cell lineage is related to IB formation. In particular, the functions of 10 candidate genes were evaluated via CRISPR-Cas9 mutants. Among those, runx2b-/- mutants completely lost IBs, while swimming performance, growth and bone mineral density were not significantly different from runx2b+/+ zebrafish. Comparative single-cell RNA sequencing (scRNA-seq) analysis in runx2b-/- and runx2b+/+ zebrafish revealed the role of osteoblasts in IB formation. In addition, differentially expressed genes were enriched in the transforming growth factor ß/bone morphogenetic protein (TGF-ß/BMP) pathway after runx2b deletion. This study provides evidence for the crucial role of runx2b regulation in IB formation. Genetic breeding can target runx2b regulation and generate strains of commercial fish species without IBs, which can improve the safe consumption and economic value of many farmed fish species.
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Bone morphogenetic protein 2 plays an important role in the regulation of osteoblast proliferation and differentiation. Phylogenetic analysis showed that the bmp2 ortholog evolved from the same ancestral gene family in vertebrates and was duplicated in teleost, which were named bmp2a and bmp2b. The results of whole-mount in situ hybridization showed that the expression locations of bmp2a and bmp2b in zebrafish were different in different periods (24 hpf, 48 hpf, 72 hpf), which revealed potential functional differentiation between bmp2a and bmp2b. Phenotypic analysis showed that bmp2a mutations caused partial rib and vertebral deformities in zebrafish, while bmp2b-/- embryos died massively after 12 hpf due to abnormal somite formation. We further explored the expression pattern changes of genes (bmp2a, bmp2b, smad1, fgf4, runx2b, alp) related to skeletal development at different developmental stages (20 dpf, 60 dpf, 90 dpf) in wild-type and bmp2a-/- zebrafish. The results showed that the expression of runx2b in bmp2a-/- was significantly downregulated at three stages and the expression of other genes were significantly downregulated at 90 dpf compared with wild-type zebrafish. The study revealed functional differentiation of bmp2a and bmp2b in zebrafish embryonic and skeletal development.
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Proteínas de Pez Cebra , Pez Cebra , Animales , Proteínas de Pez Cebra/genética , Proteínas de Pez Cebra/metabolismo , Filogenia , Proteínas Morfogenéticas Óseas/genética , Hibridación in Situ , Regulación del Desarrollo de la Expresión Génica , Proteína Morfogenética Ósea 2/genética , Proteína Morfogenética Ósea 2/metabolismoRESUMEN
Diabetes is an urgent health issue characterized by ethnic and regional variations, and is inseparable from the different dietary habits. It is worthy to note that the incidence of diabetes in Bai nationality has been reported to be much lower than Han in China. As a daily vegetable of Bai, the phytochemical and antidiabetic study of Ottelia acuminata var. acuminata had not been carried out. In this study, 41 metabolites with diverse diarylheptanoid (six new ones, Otteacumienes A-F), flavone, sesquiterpenoid, coumarin, lignan, polyacetylene, and alkaloid skeletons were characterized from O. acuminata var. acuminata. Among them, the racemic nature of 3 was characterized by chiral resolution and calculated ECD methods. The biological study revealed diarylheptanoids showed significant α-glucosidase inhibitory activities with 5 as the most effective one (60-fold stronger than acarbose). Molecular docking studies indicated that these structures have different binding cavities with acarbose. This study demonstrated that O. acuminata var. acuminata might correlated with the low incidence diabetes of Bai and the diarylheptanoids may have potential therapeutic value for diabetes mellitus.
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Bone morphogenetic protein 7 (BMP7) belongs to the transforming growth factor ß (TGF-ß) family, which not only induces cartilage and bone formation, but also regulates eye development and melanoma tumorigenesis in mammals. In teleosts, BMP7 differentiates into two subtypes, bmp7a and bmp7b, which have clearly differentiated structures. To fully understand the functional differentiation of bmp7a and bmp7b in fish species, we successfully constructed bmp7a and bmp7b gene deletion mutants in zebrafish using CRISPR/Cas9-mediated gene editing technology. Our results showed that bmp7a mutation caused abnormal development of the embryo's dorsal-ventral pattern that led to death; bmp7b mutation induced growth inhibition and increased melanin production in the skin and eye of mutants. Histological analysis revealed that melanin in the retina of the eyes in bmp7b mutants increased, and behavioral observation showed that the vision and sensitivity to food of the mutants were reduced. Transcriptome analysis of the skin and eye tissues showed that the expression changes of wnt7ba and gna14 in bmp7b mutants might promote the increase of melanin. Additionally, the eye transcriptome analysis indicated that changes in the structure of the eyes in bmp7b mutants led to defects in phototransduction, and seven DEGs (rgs9a, rgs9b, rcvrn2, guca1d, grk1b, opn1mw4, and gc2) were identified as key candidate genes that affected the photonic response of the eyes. The study revealed the functional differentiation of bmp7a and bmp7b in teleosts and the first report about the inhibitory effect of bmp7b on melanogenesis may provide useful information for the future research on human melanoma-related diseases.
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The emergence of antibiotic resistance in Staphylococcus aureus has necessitated the development of innovative anti-infective agents acting on novel targets. Alpha-hemolysin (Hla), a key virulence factor of S. aureus, is known to cause various cell damage and death. In this study, with bioassay-guided fractionation, a pair of unusual epimeric lignan trimers, ligustchuanes A and B (1 and 2), were isolated from the rhizomes of Ligusticum chuanxiong Hort, together with two known phthalides being identified by UPLC-QTOF-MS. To the best of our knowledge, trimers with rare C8-C9â³-type neolignan and ferulic acid fragments have not been identified in any natural product. Both of them were isolated as racemic mixtures, and their absolute configurations were determined by comparing experimental and calculated ECD spectra after enantioseparation. Ligustchuane B exhibited an outstanding inhibitory effect on α-hemolysin expression in both MRSA USA300 LAC and MSSA Newman strains at concentrations of 3 and 6 µM, respectively. Notably, a mouse model of infection further demonstrated that ligustchuane B could attenuate MRSA virulence in vivo.
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Due to the rapid evolution of antibiotic resistance in Staphylococcus aureus, antivirulence therapy may be a promising alternative for the effective control of the spread of resistant pathogens. The Chinese Materia Medica has been widely used for the treatment of diseases and production of health foods, and it remains a valuable resource for the discovery of compounds possessing antivirulence activity. Through a Caenorhabditis elegans infection model, an EtOAc-soluble fraction of 80% EtOH extract of Salvia miltiorrhiza Bunge (SMEA) was found to possess potential anti-infective activity against S. aureus. Then, several in vitro assays indicated that SMEA had robust antivirulence activity at the dose of 400 µg mL-1, reducing hemolytic activity and α-hemolysin expression in S. aureus. Furthermore, at 100 mg kg-1, SMEA reduced abscess formation in the main organs of mice challenged with S. aureus. In order to identify the bioactive components of SMEA and investigate the mechanisms underlying the antivirulence activity, SMEA was separated using bioassay-guided fractionation. As a result, eight compounds were identified in SMEA. Among them, tanshinone IIB (TNB) showed strong antivirulence activity both in vitro and in vivo. Furthermore, at 24 µg mL-1, TNB significantly reduced the expression of RNAIII and psmα, indicating that the mechanism underlying TNB activity was related to the accessory gene regulator quorum sensing system. In conclusion, TNB's antivirulence properties make it a promising candidate for drug development against S. aureus infections.
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Antiinfecciosos , Salvia miltiorrhiza , Infecciones Estafilocócicas , Animales , Antibacterianos/metabolismo , Antiinfecciosos/farmacología , Ratones , Percepción de Quorum , Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus aureus , VirulenciaRESUMEN
Background: With the highest mortality and metastasis rate, kidney renal clear cell carcinoma (KIRC) is one of the most common urological malignant tumors and not sensitive to chemotherapy and radiotherapy. Immunotherapy, which proves to be effective and a big progression, such as PD-1/PD-L1 inhibitors, is not sensitive to all KIRC patients. To predict prognosis and immunotherapy response, a novel immune checkpoint gene- (ICG-) related model is essential in clinics. Methods: From the public database-downloaded dataset, a novel ICG-related model for predicting prognosis and immunotherapy response in KIRC patients was built up and verified with R packages and Cox regression analysis. The Kaplan-Meier curve was plotted. Results: 39 ICGs were identified to have different expression in KIRC patients and enriched in immune-related biological pathways and activities. Three ICGs (CTLA4, TNFSF14, and HHLA2) were screened to generate KIRC-ICG model. The KIRC-ICG model was verified to be effective. With conducting KIRC-SYS model, KIRC-ICGscore was verified to be an independent factor regardless of age, gender, stage, grade, and TNM stage. Compared to the ICG-low subgroup, the ICG-high subgroup had more immune activities. KIRC-ICGscore was significantly positively correlated with the expression of Treg markers. KIRC-ICG model could also be reliable to predict immunotherapy response. Conclusion: The KIRC-ICG model was reliable to predict prognosis and immunotherapy response for KIRC patients and could be an independent factor regardless of clinical characteristics.
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Carcinoma de Células Renales , Neoplasias Renales , Humanos , Carcinoma de Células Renales/genética , Bases de Datos Factuales , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inmunoterapia , Neoplasias Renales/genética , Neoplasias Renales/terapia , Pronóstico , InmunoglobulinasRESUMEN
Here, we report a series of acceptor-donor-acceptor (A-D-A) architecture isomeric acceptors (SeCT-IC, CSeT-IC, and CTSe-IC), which have an identical electron-deficient terminal A-group and three different central D-cores with the selenophene at the innermost, relatively outer, and outermost positions of the central core, respectively. From CSeT-IC to the atom regioisomer of CTSe-IC and to the conjugated skeleton isomer of SeCT-IC, the optical band gap of neat films continuously reduced and highest occupied molecular orbitals (HOMO) gradually upshifted with changing the selenophene from relatively outer position to the outermost position and to the innermost position of the central core. More importantly, the single-crystal structure and the GIWAXS measurements revealed that CTSe-IC presents the closest π-π stacking distance, the largest CCL, and the best molecular order and crystallinity, which led to the highest electron mobility in neat films. Furthermore, the J71:CTSe-IC blend film presents a more ordered film morphology with more proper phase separation domain size, more dominant face-on orientation, and relatively higher and more balanced electron-hole mobilities in comparison with that of J71:SeCT-IC and J71:CSeT-IC. Consequently, the J71:CTSe-IC-based organic solar cell gave a superior power conversion efficiency (PCE) of 11.59%, which was obviously higher than those for J71:SeCT-IC (10.89%) and J71:CSeT-IC (8.52%). Our results demonstrate that the acceptor with selenophene in the outermost position led to significantly enhance the PCE. More importantly, rational modulation of the central fused core in combination with the conjugated skeleton isomeric method and the atom regioisomeric method provides an effective way to understand the structure-crystallinity-photovoltaic property relationship of selenophene-based regioisomers.
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A two-dimensional electron-rich fused-ring moiety (ClBDSe) based on benzo[1,2-b:4,5-b']diselenophene is synthesized. Three copolymers (PBDT-Se, PBDSe-T, and PBDSe-Se) are obtained by manipulating the connection types and number of selenophene units on the conjugated main chains with two 2D fused-ring units and two different π-bridges, respectively. In comparison with PBDT-Se and PBDSe-Se, PBDSe-T with benzo[1,2-b:4,5-b']diselenophene unit and thiophene π-bridge exhibits the deepest HOMO energy level and the strongest crystallinity in neat films. The PBDSe-T:Y6 blend film exhibits the best absorption complementarity, the most distinctive face-on orientation with proper phase separation, the highest carrier mobilities, and the lowest charge recombination among three blend films. Finally, the PBDSe-T:Y6-based device delivers an impressive power conversion efficiency (PCE) of 14.50 %, which is higher than those of PBDT-Se:Y6 and PBDSe-Se:Y6. Moreover, a decent open-circuit voltage (Voc ) of 0.89â V with a remarkably small energy loss of 0.44â eV is achieved for PBDSe-T:Y6. The efficiency of 14.50 % is the highest value for selenophene-containing copolymer-based binary organic solar cells (OSCs). This study provides evidence that introduction of 2D-benzo[1,2-b:4,5-b']diselenophene as a fused electron-rich unit with π-bridging into copolymeric donors is a valid strategy for providing high Voc and excellent PCE simultaneously in selenophene-based OSCs.
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We performed a bioinformatics analysis with validation by multiple databases, aiming to evaluate the diagnostic and prognostic value of Kelch-like ECH-associated protein 1 (Keap1) mRNA for lung cancer, and to explore possible mechanisms. Diagnostic performance of Keap1 mRNA was determined by receiver operating characteristic (ROC) curve analysis. Prognostic implication of Keap1 mRNA was estimated by Kaplan-Meier survival analysis. Co-expressed genes with both Keap1 and Nfe2L2 were identified by LinkedOmics. Mechanisms of Keap1-Nfe2L2-co-expressed genes underlying the pathogenesis of lung cancer were explored by function enrichment and pathway analysis. The ROC curve analysis determined a good diagnostic performance of Keap1 mRNA for lung squamous cell carcinoma (LUSC), with an area under the ROC curve (AUC) of 0.833, sensitivity of 72.7%, and specificity of 90.6% (P<0.001). Multivariate Cox regression recognized high Keap1 mRNA to be an independent risk factor of mortality for overall lung cancer [hazard ratio (HR): 11.034, P=0.044], but an independent antagonistic factor for lung adenocarcinoma (LUAD) (HR: 0.404, P<0.001). Validation by UALCAN and GEPIA supported Oncomine findings regarding the diagnostic value of Keap1 mRNA for LUSC, but denied its prognostic value. After screening, we identified 17 co-expressed genes with both Keap1 and Nfe2L2 for LUAD, and 22 for LUSC, mainly enriched in signaling pathway of oxidative stress-induced gene expression via Nrf2. In conclusion, Keap1 mRNA has a good diagnostic performance, but controversial prognostic efficacy for LUSC. The pathogenesis of lung cancer is associated with Keap1-Nfe2L2-co-expressed genes by signaling pathway of oxidative stress-induced gene expression via Nrf2.
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Adenocarcinoma del Pulmón/genética , Carcinoma de Células Escamosas/genética , Proteína 1 Asociada A ECH Tipo Kelch/genética , Factor 2 Relacionado con NF-E2/genética , Adenocarcinoma del Pulmón/diagnóstico , Adenocarcinoma del Pulmón/patología , Biomarcadores de Tumor/genética , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patología , Biología Computacional , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Estimación de Kaplan-Meier , Masculino , Análisis por Micromatrices , Supervivencia sin Progresión , Modelos de Riesgos Proporcionales , ARN Mensajero/genéticaRESUMEN
Guttiferone F, a natural polyprenylated polycyclic acylphloroglucinol, was originally assigned as the 30-epimer of garcinol by NMR data analyses. Conversion of guttiferone F in the presence of acid afforded its cyclized form (2a), which was previously assigned as 30-epi-cambogin. However, the absolute configurations of guttiferone F and 2a have not been determined. Reinvestigation of the structures of those two compounds, using X-ray and NMR data analyses and chemical transformation, revealed that the original assignment of the C-30 absolute configuration in guttiferone F and 2a should be inverted. Guttiferone F is indeed garcinol, and 2a, which was previously identified as 30-epi-cambogin, is cambogin.
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Benzofenonas/química , Garcinia/química , Terpenos/química , China , Estructura MolecularRESUMEN
One new xanthone, (±) garciesculenxanthone C (1), two new biphenyls, garciesculenbiphenyls A (2) and B (3), together with two known compounds, doitungbiphenyl B (4) and morusignin D (5), were isolated from Garcinia esculenta. The structures of new compounds were elucidated by spectroscopic analysis, and the absolute configuration of (±) garciesculenxanthone C (1) was assigned by a modified Mosher's method. All isolates were evaluated for their antistaphylococcal activities against Staphylococcus aureus Newman, USA300 LAC, USA400 MW2, and Mu50 strains. Among these, (±) garciesculenxanthone C (1) showed the best antistaphylococcal activity, and its effect was determined to be bactericidal by time-kill experiment.
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Antibacterianos/farmacología , Compuestos de Bifenilo/aislamiento & purificación , Compuestos de Bifenilo/farmacología , Garcinia/química , Prenilación , Staphylococcus aureus/efectos de los fármacos , Xantonas/aislamiento & purificación , Xantonas/farmacología , Antibacterianos/química , Compuestos de Bifenilo/química , Espectroscopía de Resonancia Magnética con Carbono-13 , Pruebas de Sensibilidad Microbiana , Estereoisomerismo , Xantonas/químicaRESUMEN
Coronavirus disease-2019 (COVID-19) is a new highly infectious disease caused by a novel coronavirus. Recently, the number of new cases infected pneumonia in the world continues to increase, which has aroused great concern from the international community. At present, there are no small-molecule specific anti-viral drugs for the treatment. The high mortality rate seriously threatens human health. Traditional Chinese medicine (TCM) is a unique health resource in China. The combination of TCM and Western medicine has played a positive and important role in combating COVID-19 in China. In this review, through literature mining and analysis, it was found that TCM has the potential to prevent and treat the COVID-19. Then, the network pharmacological studies demonstrated that TCM played roles of anti-virus, anti-inflammation and immunoregulation in the management of COVID-19 via multiple components acting on multiple targets and multiple pathways. Finally, clinical researches also confirmed the beneficial effects of TCM on the treatment of patients. This review may provide meaningful and useful information on further drug development of COVID-19 and other viral infectious diseases.