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1.
Plant Physiol ; 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39222356

RESUMEN

Maize (Zea mays L.) kernel development is a complex and dynamic process involving cell division and differentiation, into a variety of cell types. Epigenetic modifications, including DNA methylation, play a pivotal role in regulating this process. N6-methyladenosine modification is a universal and dynamic post-transcriptional epigenetic modification that is involved in the regulation of plant development. However, the role of N6-methyladenosine in maize kernel development remains unknown. In this study, we have constructed transcriptome-wide profiles for maize kernels at various stages of early development. Utilizing a combination of MeRIP-seq and RNA-seq analysis, we identified a total of 11,170, 10,973, 11,094, 11,990, 12,203 and 10,893 N6-methyladenosine peaks in maize kernels at 0, 2, 4, 6, 8, and 12 days after pollination, respectively. These N6-methyladenosine modifications were primarily deposited at the 3'-UTRs and were associated with the conserved motif-UGUACA. Additionally, we found that conserved N6-methyladenosine modification are involved in the regulation of genes that are ubiquitously expressed during kernel development. Further analysis revealed that N6-methyladenosine peak intensity was negatively correlated with the mRNA abundance of these ubiquitously expressed genes. Meanwhile, we employed phylogenetic analysis to predict potential regulatory proteins involved in maize kernels development and identified several that participate in the regulation of N6-methyladenosine modifications. Collectively, our results suggest the existence of a novel post-transcriptional epigenetic modification mechanism involved in the regulation of maize kernels development, thereby providing a novel perspective for maize molecular breeding.

2.
Artículo en Inglés | MEDLINE | ID: mdl-39141462

RESUMEN

Graph classification is a critical task in numerous multimedia applications, where graphs are employed to represent diverse types of multimedia data, including images, videos, and social networks. Nevertheless, in the real world, labeled graph data are always limited or scarce. To address this issue, we focus on the semi-supervised graph classification task, which involves both supervised and unsupervised models learning from labeled and unlabeled data. In contrast to recent approaches that transfer the entire knowledge from the unsupervised model to the supervised one, we argue that an effective transfer should only retain the relevant semantics that align well with the supervised task. We introduce a novel framework termed in this article, which learns disentangled representation for semi-supervised graph classification. Specifically, a disentangled graph encoder is proposed to generate factorwise graph representations for both supervised and unsupervised models. Then, we train two models via supervised objective and mutual information (MI)-based constraints, respectively. To ensure the meaningful transfer of knowledge from the unsupervised encoder to the supervised one, we further define an MI-based disentangled consistency regularization between two models and identify the corresponding rationale that aligns well with the current graph classification task. Experiments conducted on various publicly available datasets demonstrate the effectiveness of our .

3.
Asian J Androl ; 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39091143

RESUMEN

Parameters of peripheral blood cell have been shown as the potential predictors of erectile dysfunction (ED). To investigate the clinical significance of hematological parameters for predicting the risk of rapid ejaculation, we established a rat copulatory model on the basis of ejaculation distribution theory. Blood samples from different ejaculatory groups were collected for peripheral blood cell counts and serum serotonin (5-HT) tests. Meanwhile, the relationship between hematological parameters and ejaculatory behaviors was assessed. Final analysis included 11 rapid ejaculators, 10 normal ejaculators, and 10 sluggish ejaculators whose complete data were available. The platelet (PLT) count in rapid ejaculators was significantly lower than that in normal and sluggish ejaculators, whereas the platelet distribution width (PDW) and mean platelet volume (MPV) were significantly greater in rapid ejaculators. Multivariate logistic regression analysis and receiver operating characteristic (ROC) curve analysis showed that the PLT was an independent protective factor for rapid ejaculation. Meanwhile, rapid ejaculators were found to have the lowest serum 5-HT compared to normal and sluggish ejaculators (P < 0.001). Furthermore, there was a positive correlation between the PLT and serum 5-HT (r = 0.662, P < 0.001), indicating that the PLT could indirectly reflect the serum 5-HT concentration. In addition, we assessed the association between the PLT and ejaculatory parameters. There was a negative correlation between ejaculation frequency (EF) and the PLT (r = -0.595, P < 0.001), whereas there was a positive correlation between ejaculation latency (EL) and the PLT (r = 0.740, P < 0.001). This study indicated that the PLT might be a useful and convenient diagnostic marker for predicting the risk of rapid ejaculation.

4.
Respir Res ; 25(1): 275, 2024 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-39003443

RESUMEN

Pleurisy can be categorized as primary or secondary, arising from immunological, tumorous, or microbial conditions. It often results in lung structure damage and the development of various respiratory issues. Among the different types, tuberculous pleurisy has emerged as a prominent focus for both clinical and scientific investigations. The IL-10 family, known for its anti-inflammatory properties in the human immune system, is increasingly being studied for its involvement in the pathogenesis of pleurisy. This review aims to present a detailed overview of the intricate role of IL-10 family members (specifically IL-10, IL-22, and IL-26) in human and animal pleuritic diseases or relevant animal models. These insights could serve as valuable guidance and references for further studies on pleurisy and potential therapeutic strategies.


Asunto(s)
Interleucina-10 , Interleucina-22 , Interleucinas , Tuberculosis Pleural , Animales , Humanos , Interleucina-10/metabolismo , Interleucinas/metabolismo , Interleucinas/inmunología , Pleuresia/inmunología , Pleuresia/diagnóstico , Pleuresia/metabolismo , Tuberculosis Pleural/diagnóstico , Tuberculosis Pleural/inmunología , Tuberculosis Pleural/metabolismo , Tuberculosis Pleural/tratamiento farmacológico
5.
J Asian Nat Prod Res ; : 1-8, 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38963349

RESUMEN

The preliminary study revealed that the ethyl acetate eluate of Youngia japonica (YJ-E) could inhibit the expression of key proteins of p-p65, p-IκBα, p-IKKα/ß, and p-AKT in LPS stimulated BV2 cell. Further phytochemical study led to the isolation of eight compounds from YJ-E, including one new sesquiterpene lactone. Their structures were elucidated by several spectroscopic data, and comparing the NMR data of known compound. In addition, all of the isolates were evaluated for the anti-inflammatory effect. As a result, compounds 3 and 4 distinctly attenuated the expressions of p-IκBα, p-p65, and p-AKT in LPS stimulated BV2 cell, respectively.

6.
Chem Biodivers ; : e202401063, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38924351

RESUMEN

In the process of searching for anti-breast cancer agents, five sesquiterpene lactones (1-5), including two previously undescribed ones, yjaponica B-C (1-2), were isolated from the herb of Youngia japonica. Their structures were elucidated by spectroscopic data analyses and Marfey's method. Cytotoxic activities of all compounds against A549, U87, and 4T1 cell lines were tested using the CCK8 assay. The result showed that compound 3 possessed the highest cytotoxic activity against 4T1 cells with an IC50 value of 10.60 µM. Furthermore, compound 3 distinctly induced apoptosis, inhibited immigration, and blocked the cell cycle of 4T1 cells. In addition, compound 3 induced the production of reactive oxygen species. Further anticancer mechanism studies showed that compound 3 significantly upregulated expression of the cleaved caspase 3 and PARP, whereas it downregulated the expression of Bcl-2, cyclin D1, cyclin A2, CDK4, and CDK2. Taken together, our results demonstrate that compound 3 has a high potential of being used as a leading compound for the discovery of new anti-breast cancer agent.

7.
Artículo en Inglés | MEDLINE | ID: mdl-38833395

RESUMEN

Hashing has received significant interest in large-scale data retrieval due to its outstanding computational efficiency. Of late, numerous deep hashing approaches have emerged, which have obtained impressive performance. However, these approaches can contain ethical risks during image retrieval. To address this, we are the first to study the problem of group fairness within learning to hash and introduce a novel method termed Fairness-aware Hashing with Mixture of Experts (FATE). Specifically, FATE leverages the mixture-of-experts framework as the hashing network, where each expert contributes knowledge from an individual viewpoint, followed by aggregation using the gating mechanism. This strongly enhances the model capability, facilitating the generation of both discriminative and unbiased binary descriptors. We also incorporate fairness-aware contrastive learning, combining sensitive labels with feature similarities to ensure unbiased hash code learning. Furthermore, an adversarial learning objective condition on both deep features and hash codes is employed to further eliminate group biases. Extensive experiments on several benchmark datasets validate the superiority of the proposed FATE compared with various state-of-the-art approaches.

8.
BMC Plant Biol ; 24(1): 458, 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38797860

RESUMEN

BACKGROUND: The endosperm serves as the primary source of nutrients for maize (Zea mays L.) kernel embryo development and germination. Positioned at the base of the endosperm, the transfer cells (TCs) of the basal endosperm transfer layer (BETL) generate cell wall ingrowths, which enhance the connectivity between the maternal plant and the developing kernels. These TCs play a crucial role in nutrient transport and defense against pathogens. The molecular mechanism underlying BETL development in maize remains unraveled. RESULTS: This study demonstrated that the MYB-related transcription factor ZmMYBR29, exhibited specific expression in the basal cellularized endosperm, as evidenced by in situ hybridization analysis. Utilizing the CRISPR/Cas9 system, we successfully generated a loss-of-function homozygous zmmybr29 mutant, which presented with smaller kernel size. Observation of histological sections revealed abnormal development and disrupted morphology of the cell wall ingrowths in the BETL. The average grain filling rate decreased significantly by 26.7% in zmmybr29 mutant in comparison to the wild type, which impacted the dry matter accumulation within the kernels and ultimately led to a decrease in grain weight. Analysis of RNA-seq data revealed downregulated expression of genes associated with starch synthesis and carbohydrate metabolism in the mutant. Furthermore, transcriptomic profiling identified 23 genes that expressed specifically in BETL, and the majority of these genes exhibited altered expression patterns in zmmybr29 mutant. CONCLUSIONS: In summary, ZmMYBR29 encodes a MYB-related transcription factor that is expressed specifically in BETL, resulting in the downregulation of genes associated with kernel development. Furthermore, ZmMYBR29 influences kernels weight by affecting the grain filling rate, providing a new perspective for the complementation of the molecular regulatory network in maize endosperm development.


Asunto(s)
Grano Comestible , Endospermo , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas , Factores de Transcripción , Zea mays , Zea mays/genética , Zea mays/crecimiento & desarrollo , Zea mays/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Grano Comestible/genética , Grano Comestible/crecimiento & desarrollo , Grano Comestible/metabolismo , Endospermo/genética , Endospermo/crecimiento & desarrollo , Endospermo/metabolismo , Pared Celular/metabolismo , Pared Celular/genética , Semillas/genética , Semillas/crecimiento & desarrollo , Semillas/metabolismo , Sistemas CRISPR-Cas
9.
Zhongguo Zhong Yao Za Zhi ; 49(8): 2188-2196, 2024 Apr.
Artículo en Chino | MEDLINE | ID: mdl-38812234

RESUMEN

This study aims to investigate the protective effect of salidroside(SAL) on renal damage in diabetic nephropathy(DN) mice based on the receptor for advanced glycation end products/janus activated kinase 1/signal transduction and activator of transcription 3(RAGE/JAK1/STAT3) signaling pathway. The mouse DN model was established by high-fat/high-sucrose diets combined with intraperitoneal injection of streptozocin(STZ). Mice were randomly divided into normal group, model group, low-dose SAL group(20 mg·kg~(-1)), high-dose SAL group(100 mg·kg~(-1)), and metformin group(140 mg·kg~(-1)), with 12 mice in each group. After establishing the DN model, mice were given drugs or solvent intragastrically, once a day for consecutive 10 weeks. Body weight, daily water intake, and fasting blood glucose(FBG) were measured every two weeks. After the last dose, the glucose tolerance test was performed, and the samples of 24-hour urine, serum, and kidney tissue were collected. The levels of 24 hours urinary total protein(24 h-UTP), serum creatinine(Scr), blood urea nitrogen(BUN), triglyceride(TG), total cholesterol(TC), low density lipoprotein cholesterol(LDL-C), and high density lipoprotein cholesterol(HDL-C) were detected by biochemical tests. Periodic acid-schiff(PAS) staining was used to observe the pathological changes in the kidney tissue. The protein expressions of α-smooth muscle actin(α-SMA), vimentin, and advanced glycation end products(AGEs) in kidneys were detected by immunohistochemical staining. The activities of superoxide dismutase(SOD), catalase(CAT), glutathione peroxidase(GSH-PX), and the level of malondialdehyde(MDA) in kidneys were detected by using a corresponding detection kit. Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of AGEs, carboxymethyllysine(CML), and carboxyethyllysine(CEL) in serum. The protein expressions of RAGE and the phosphorylation level of JAK1 and STAT3 in kidneys were detected by Western blot. Compared with the normal group, the levels of FBG, the area under the curve of glucose(AUCG), water intake, kidney index, 24 h-UTP, tubular injury score, extracellular matrix deposition ratio of the renal glomerulus, the serum levels of Scr, BUN, TG, LDL-C, AGEs, CEL, and CML, the level of MDA, the protein expressions of α-SMA, vimentin, AGEs, and RAGE, and the phosphorylation level of JAK1 and STAT3 in kidney tissue were increased significantly(P<0.01), while the level of HDL-C in serum and the activity of SOD, CAT, and GSH-PX in kidney tissue were decreased significantly(P<0.01). Compared with the model group, the above indexes of the high-dose SAL group were reversed significantly(P<0.05 or P<0.01). In conclusion, this study suggests that SAL can alleviate oxidative stress and renal fibrosis by inhibiting the activation of AGEs-mediated RAGE/JAK1/STAT3 signaling axis, thus playing a potential role in the treatment of DN.


Asunto(s)
Nefropatías Diabéticas , Glucósidos , Janus Quinasa 1 , Riñón , Fenoles , Receptor para Productos Finales de Glicación Avanzada , Factor de Transcripción STAT3 , Transducción de Señal , Animales , Ratones , Nefropatías Diabéticas/tratamiento farmacológico , Nefropatías Diabéticas/metabolismo , Glucósidos/farmacología , Glucósidos/administración & dosificación , Receptor para Productos Finales de Glicación Avanzada/metabolismo , Receptor para Productos Finales de Glicación Avanzada/genética , Transducción de Señal/efectos de los fármacos , Masculino , Riñón/efectos de los fármacos , Riñón/metabolismo , Riñón/patología , Fenoles/farmacología , Janus Quinasa 1/metabolismo , Janus Quinasa 1/genética , Factor de Transcripción STAT3/metabolismo , Factor de Transcripción STAT3/genética , Sustancias Protectoras/farmacología , Sustancias Protectoras/administración & dosificación , Humanos , Ratones Endogámicos C57BL , Glucemia/metabolismo , Glucemia/efectos de los fármacos
10.
Nat Commun ; 15(1): 2913, 2024 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-38575609

RESUMEN

Carbaporphyrin dimers, investigated for their distinctive electronic structures and exceptional properties, have predominantly consisted of systems containing identical subunits. This study addresses the associated knowledge gap by focusing on asymmetric carbaporphyrin dimers with Janus-like characteristics. The synthesis of a Janus-type carbaporphyrin pseudo-dimer 5 is presented. It displays antiaromatic characteristics on the fused side and nonaromatic behavior on the unfused side. A newly synthesized tetraphenylene (TPE) linked bis-dibenzihomoporphyrin 8 and a previously reported dibenzo[g,p]chrysene (DBC) linked bis-dicarbacorrole 9 were prepared as controls. Comprehensive analyses, including 1H NMR spectral studies, single crystal X-ray diffraction analyses, and DFT calculations, validate the mixed character of 5. A further feature of the Janus pseudo-dimer 5 is that it may be transformed into a heterometallic complex, with one side coordinating a Cu(III) center and the other stabilizing a BODIPY complex. This disparate regiochemical reactivity underscores the potential of carbaporphyrin dimers as versatile frameworks, with electronic features and site-specific coordination chemistry controlled through asymmetry. These findings position carbaporphyrin dimers as promising candidates for advances in electronic structure studies, coordination chemistry, materials science, and beyond.

11.
Chemistry ; 30(35): e202401240, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38632105

RESUMEN

A triply linked dicarbacorrole dimer (7) was synthesized from a new meso-meso singly linked dicarbacorrole dimer precursor (6) via an oxidative fusion reaction by 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) in the presence of trifluoromethanesulfonic acid (TfOH). Single crystal X-ray structure of 7 adopts a flat conformation with a length as ca. 15.946 Šand a width as 6.903 Å, which can be regarded as a short carbaporphyrinoid tape. Two coordinated Cu ions keeps the +3 oxidation state in 7, as confirmed by NMR spectroscopy, single crystal X-ray diffraction and X-ray photoelectron spectroscopy (XPS). This is in sharp contrast to the Osuka's triply linked tetrapyrrolic corrole dimers, where the inner 3NH form is not stable and thus can only act as a divalent ligand. Due to the non-aromatic nature of dicarbacorrole macrocycle, the largely decreased HOMO-LUMO gap and red-shifted absorption of 7 are best ascribed to the strong electronic interaction between two dipyrromethene-type chromophores. To our knowledge, this is the first fully fused carbaporphyrinoid dimer with ß-ß, meso-meso, ß-ß triply linkages prepared to date.

12.
New Phytol ; 242(3): 1098-1112, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38515249

RESUMEN

The potential for totipotency exists in all plant cells; however, the underlying mechanisms remain largely unknown. Earlier findings have revealed that the overexpression of LEAFY COTYLEDON 2 (LEC2) can directly trigger the formation of somatic embryos on the cotyledons of Arabidopsis. Furthermore, cotyledon cells that overexpress LEC2 accumulate significant lipid reserves typically found in seeds. The precise mechanisms and functions governing lipid accumulation in this process remain unexplored. In this study, we demonstrate that WRINKLED1 (WRI1), the key regulator of lipid biosynthesis, is essential for somatic embryo formation, suggesting that WRI1-mediated lipid biosynthesis plays a crucial role in the transition from vegetative to embryonic development. Our findings indicate a direct interaction between WRI1 and LEC2, which enhances the enrichment of LEC2 at downstream target genes and stimulates their induction. Besides, our data suggest that WRI1 forms a complex with LEC1, LEC2, and FUSCA3 (FUS3) to facilitate the accumulation of auxin and lipid for the somatic embryo induction, through strengthening the activation of YUCCA4 (YUC4) and OLEOSIN3 (OLE3) genes. Our results uncover a regulatory module controlled by WRI1, crucial for somatic embryogenesis. These findings provide valuable insights into our understanding of plant cell totipotency.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Proteínas de Arabidopsis/metabolismo , Regulación de la Expresión Génica de las Plantas , Ácidos Indolacéticos , Lípidos , Semillas/genética , Factores de Transcripción/metabolismo
13.
Int J Biol Macromol ; 264(Pt 1): 130475, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38428764

RESUMEN

Deep eutectic solvents (DES) are promising green solvents for depolymerization and reconstruction of lignin. Revealing the transformations of lignin during DES treatment is beneficial for high potential lignin applications. In this study, bagasse lignin was treated with a binary DES and three ternary DESs, respectively. The results showed that net hydrogen bonding acidity(α-ß) value of DES was positively correlated to the increment of phenolic hydroxyl of lignin, and the ternary DES of choline chloride-formic acid-oxalic acid (ChCl-FA-OA) exhibited the best phenolation performances. The phenolic hydroxyl content of ChCl-FA-OA treated lignin was increased by 50.4 %, reaching 2.41 mmol/g under optimum conditions (120 °C, 4 h, ChCl-FA-OA = 1:2:1). Moreover, it was found that the cleavage of ß-O-4' aryl ether bond and ester bond were dominant reactions during the treatment, accompanied by condensation reactions. Additionally, the obtained lignin oil contained various syringyl and guaiacyl derived phenolic compounds. Especially, the content of acetovanillone in lignin oil reached 29.94 %, much higher than in previous studies. Finally, the degradation mechanism of lignin in ChCl-FA-OA system was proposed. The present work provided insights into the relationship between lignin phenolation and DES properties. The novel ChCl-FA-OA system can achieve efficient lignin depolymerization, and convert lignin biomass into value-added chemical products.


Asunto(s)
Disolventes Eutécticos Profundos , Lignina , Lignina/química , Solventes/química , Fenoles , Colina/química , Biomasa , Ácido Oxálico , Hidrólisis
14.
Plant Physiol ; 195(2): 1642-1659, 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38431524

RESUMEN

Maize (Zea mays) smut is a common biotrophic fungal disease caused by Ustilago maydis and leads to low maize yield. Maize resistance to U. maydis is a quantitative trait. However, the molecular mechanism underlying the resistance of maize to U. maydis is poorly understood. Here, we reported that a maize mutant caused by a single gene mutation exhibited defects in both fungal resistance and plant development. maize mutant highly susceptible to U. maydis (mmsu) with a dwarf phenotype forms tumors in the ear. A map-based cloning and allelism test demonstrated that 1 gene encoding a putative arogenate dehydratase/prephenate dehydratase (ADT/PDT) is responsible for the phenotypes of the mmsu and was designated as ZmADT2. Combined transcriptomic and metabolomic analyses revealed that mmsu had substantial differences in multiple metabolic pathways in response to U. maydis infection compared with the wild type. Disruption of ZmADT2 caused damage to the chloroplast ultrastructure and function, metabolic flux redirection, and reduced the amounts of salicylic acid (SA) and lignin, leading to susceptibility to U. maydis and dwarf phenotype. These results suggested that ZmADT2 is required for maintaining metabolic flux, as well as resistance to U. maydis and plant development in maize. Meanwhile, our findings provided insights into the maize response mechanism to U. maydis infection.


Asunto(s)
Resistencia a la Enfermedad , Enfermedades de las Plantas , Zea mays , Zea mays/microbiología , Zea mays/genética , Zea mays/crecimiento & desarrollo , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/genética , Enfermedades de las Plantas/inmunología , Resistencia a la Enfermedad/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Hidroliasas/genética , Hidroliasas/metabolismo , Basidiomycota/fisiología , Regulación de la Expresión Génica de las Plantas , Fenotipo , Mutación/genética , Ácido Salicílico/metabolismo , Ustilago/genética
15.
Fitoterapia ; 174: 105869, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38378132

RESUMEN

Fourteen sesquiterpenes, including one undescribed sesquiterpene lactone, were isolated from Youngia japonica, and their structures were identified by NMR, HRESIMS, ECD and calculated ECD. Cytotoxic activities of all isolates against A549, HeLa, and 4 T1 cell lines were detected by CCK8 assay. Among them, 2 showed obvious cytotoxic activity against A549 cells. Subsequently, the production of ROS, and apoptosis of A549 cells treated with 2 were evaluated. The result showed that 2 distinctly increased the ROS level, and induced the apoptosis of A549 cells. Further anticancer mechanism studies showed that 2 increased the expression of cleaved caspase 3. Taken together, our results demonstrated that 2 might become potential leading compounds for the treatment of lung cancer.


Asunto(s)
Antineoplásicos , Asteraceae , Sesquiterpenos , Humanos , Línea Celular Tumoral , Estructura Molecular , Especies Reactivas de Oxígeno , Antineoplásicos/farmacología , Apoptosis , Sesquiterpenos/farmacología , Sesquiterpenos/química
16.
J Ethnopharmacol ; 325: 117805, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38278374

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Colorectal cancer (CRC) belongs to the category of intestinal wind, anal ulcer, abdominal mass and other diseases in traditional Chinese medicine (TCM). Floris Sophorae Powder (F.S), is a classical prescription is recorded in Puji Benshi Fang for the treatment of intestinal carbuncle. It has been incorporated into the prescriptions for the treatment of intestinal diseases and achieved remarkable results in modern medicine. However, the mechanism of F.S in the treatment of colorectal cancer remains unclear and requires further study. AIM OF THE STUDY: To investigate F.S in treating CRC and clarify the underlying mechanism. MATERIALS AND METHODS: This study was based on Dextran Sulfate Sodium Salt (DSS) combined with Azoxymethane (AOM) induced CRC mouse model to clarify the pharmacological effects of F.S. The serum metabolomics was used to study the mechanism of action, and the chemical composition of F.S was found by UPLC-Q-TOF-MS. The rationality of serm metabolomics results was verified through the clinical target database of network pharmacology, and the upstream and downstream targets of related pathways were found. The mechanism pathway was verified by Western blot to clarify its mechanism of action. RESULTS: In vivo pharmacological experiments showed that F.S inhibited tumor growth and improved hematochezia. The vital signs of mice in the high-dose F.S group approached to those in the control group. A total of 43 differential metabolites were found to be significantly changed by serum metabolomics. F.S could modulate and recover most of the differential metabolites, which proved to be closely related to the KRAS/MEK-ERK signaling pathway. A total of 46 compounds in F.S were identified, and the rationality of serm metabolic pathway was verified by network pharmacology. Western blot results also verified that the expression of KRAS, E2F1, p-MEK and p-ERK were significantly decreased after F.S treatment. CONCLUSION: Classical prescription Floris Sophorae Powder treat colorectal cancer by regulating KRAS/MEK-ERK signaling pathway.


Asunto(s)
Neoplasias Colorrectales , Medicamentos Herbarios Chinos , Animales , Ratones , Polvos/uso terapéutico , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , Moduladores Selectivos de los Receptores de Estrógeno/uso terapéutico , Transducción de Señal , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Neoplasias Colorrectales/metabolismo , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico
17.
Bioorg Chem ; 144: 107116, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38237391

RESUMEN

Four undescribed coumarin derivatives, ficusalt A (1) and ficusalt B (2), a pair of racemic coumarins, (±) ficudimer A (3a/3b), along with ten known amides, were isolated from the roots of Ficus hirta. Their structures were elucidated by several spectroscopic data analyses, including HRESIMS, NMR, and X-ray single-crystal diffraction. The cytotoxic activities of all compounds against HeLa, HepG2, MCF-7, and H460 cell lines were detected using the MTT assay. Among these, 5 showed the highest activity against HeLa cells. Subsequently, the apoptotic, anti-invasive, and anti-migration effects of 5 on HeLa cells were determined by flow cytometer, transwell invasion assay, and wound-healing assay, respectively. The result suggested that 5 distinctly induced the apoptosis in HeLa cells and inhibited their invasion and migration. Further studies on anticancer mechanisms were conducted using Western blotting. As a result, 5 increased the cleavage of PARP and the expression of pro-apoptotic protein Bax. Moreover, 5 notably upregulated the phosphorylation of p38 and JNK, whereas inhibited the expression of p-ERK and p-AKT. Our results demonstrated that 5 could be a potential leading compound for further application in the treatment of cervical cancer.


Asunto(s)
Antineoplásicos , Ficus , Femenino , Humanos , Células HeLa , Ficus/química , Amidas/farmacología , Cumarinas/farmacología , Antineoplásicos/farmacología , Antineoplásicos/química , Apoptosis
19.
IEEE Trans Pattern Anal Mach Intell ; 46(4): 2333-2347, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37943653

RESUMEN

This paper delves into the problem of correlated time-series forecasting in practical applications, an area of growing interest in a multitude of fields such as stock price prediction and traffic demand analysis. Current methodologies primarily represent data using conventional graph structures, yet these fail to capture intricate structures with non-pairwise relationships. To address this challenge, we adopt dynamic hypergraphs in this study to better illustrate complex interactions, and introduce a novel hypergraph neural network model named CHNN for correlated time series forecasting. In more detail, CHNN leverages both semantic and topological similarities via an interaction model and hypergraph diffusion process, thereby constructing comprehensive collaborative correlation scores that effectively guide spatial message propagation. In addition, it incorporates short-term temporal information to generate efficient spatio-temporal feature maps. Lastly, a long-term temporal module is proposed to generate future predictions utilizing both temporal attention and a gated recurrent network. Comprehensive experiments conducted on four real-world datasets, i.e., Tiingo, Stocktwits, NYC-Taxi, and Social Network demonstrate that the proposed CHNN markedly outperforms a range of benchmark methods.

20.
J Am Chem Soc ; 146(1): 543-551, 2024 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-38147538

RESUMEN

A nanographene-fused expanded carbaporphyrin (5) and its BF2 complex (6) were synthesized. Single-crystal X-ray structures revealed that 5 and 6 are connected by two hexa-peri-hexabenzocoronene (HBC) units and two dipyrromethene or BODIPY units, respectively. As prepared, 5 and 6 both show nonaromatic character with figure-of-eight carbaoctaphyrin (1.1.1.0.1.1.1.0) cores and adopt tweezers-like conformations characterized by a partially confined space between the two constituent HBC units. The distance between the HBC centers is >10 Å, while the dihedral angles between the two HBC planes are 30.5 and 35.2° for 5 and 6, respectively. The interactions between 5 and 6 and fullerene C60 were studied both in organic media and in the solid state. Proton NMR spectral titrations of 5 and 6 with C60 revealed a 1:1 binding mode for both macrocycles. In toluene-d8, the corresponding binding constants were determined to be 1141 ± 17 and 994 ± 10 M-1 for 5 and 6, respectively. Single-crystal X-ray diffraction structural analyses confirmed the formation of 1:1 fullerene inclusion complexes in the solid state. The C60 guests in both complexes are found within triangular pockets composed of two HBC units from the tweezers-like receptor most closely associated with the bound fullerene, as well as an HBC unit from an adjacent host. Femtosecond transient absorption measurements revealed subpicosecond ultrafast charge separation between 5 (and 6) and C60 in the complexes. To the best of our knowledge, the present report provides the first example wherein a nanographene building block is incorporated into the core of a porphyrinic framework.

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