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1.
Polymers (Basel) ; 16(14)2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-39065289

RESUMEN

A polysaccharide (CP2-S), consisting of glucose with a weight average molecular weight of 5.9 × 106, was purified from the fruit bodies of Cordyceps militaris. In this work, the corresponding structure and anti-tumor activity in vivo were investigated. Methylation and NMR analysis revealed that CP2-S was composed of a →4)-α-D-Glcp-(1→ backbone with partial substitution occurring at O-6 by T-linked α-D-Glcp in every ten residues, which has not been reported in previous reports. In vivo anti-tumor experiments showed that CP2-S could inhibit the growth of Lewis lung carcinoma in mice. Tumor inhibition rates were 17.8%, 24.5%, and 29.5% at dosages of 12.5, 50, and 100 mg/kg/d, respectively. Compared with the cisplatin group, mice treated with CP2-S exhibited a significant increase in spleen index (increased 22.7-42.4%) and thymus index (increased 47.7-36.8%). Additionally, serum levels of IgM and IgG in tumor-bearing mice increased by approximately 6.11~10.75-folds and 1.31~1.38-folds, respectively. These findings prove that CP2-S significantly inhibited the growth of Lewis lung carcinoma through immune-enhancing activity in mice.

2.
Stress Health ; : e3454, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39078475

RESUMEN

Depression is closely related to individual social functions. The current study aimed to examine whether depression is associated with ostracism, whether interpretation bias mediates this relationship, and whether trait mindfulness moderates direct and indirect relationships between depression and ostracism. Overall, 389 Chinese college students completed the Center for Epidemiological Survey, Depression Scale, Interpretation Bias Questionnaire, Philadelphia mindfulness scale, and perceived ostracism scale at two-time points. Latent Profile analysis and moderated mediation analysis were performed. After controlling for sex and age, depression (t1) was positively correlated to perceived ostracism, with this relationship being partially mediated by negative interpretation bias (IBN, t2). The effect of IBN on perceived ostracism was weak when awareness was high at time 2. Acceptance had a non-significant moderating role in the relationship between IBN and perceived ostracism at time 2. LPA delineated three profiles: high awareness, high acceptance, and medium mindfulness. The moderating role of the different profiles in the relationship between IBN (t2) and perceived ostracism (t2) was significant. Depressed individuals appear to experience more ostracism because of IBN. Awareness might alleviate the effect of IBN on perceived ostracism.

3.
Spectrochim Acta A Mol Biomol Spectrosc ; 322: 124765, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-39018670

RESUMEN

Excessive use of gentamicin sulfate can cause severe nephrotoxicity and ototoxicity, abnormal levels of Fe3+ intake can also cause serious damage to body. Therefore, establishing a fast and accurate detection method for the above-mentioned substances is of great significance. However, traditional detection methods such as high-performance liquid chromatography still have certain problems such as high cost and complex operation. Fluorescent MOFs are favored by analysts due to their high specific surface area, high porosity, adjustable pore size, and good stability. In this paper, we have synthesized four rare earth MOFs based on the pyridinecarboxylic acid ligand (H2L), which are [Eu(L)1/2H2O]n, [Gd(L)1/2H2O]n, [Sm(L)1/2H2O]n, [Y(L)3/2H2O·DMF]n. The structures of four MOFs were confirmed by single crystal X-ray diffraction, which proved that MOF-1, MOF-2 and MOF-3 were isostructural, and all the four MOFs were three-dimensional structures. In the fluorescence test, gentamicin sulfate and Fe3+ can cause significant fluorescence quenching of MOF-1 and MOF-4 respectively, and show good selectivity and anti-interference performance, as well as low detection limit and wide detection range. This work may provide a possibility for the detection of gentamicin sulfate and iron ions in complex environments.

4.
Opt Lett ; 49(13): 3701-3704, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38950246

RESUMEN

We presented the first, to our knowledge, demonstration of an ultraviolet (UV) laser at 223.8 nm by six-harmonic generation of an electro-optic Q-switched cavity dumping 1342 nm Nd:YVO4 laser. It offers high power, constant short pulse duration, and adjustable pulse repetition rate. The pulse duration is independent of the pump power and repetition rate compared to classical Q-switched oscillators. The output efficiency of the UV laser is optimized by adjusting the focusing lens. With the incident pump power of 30 W, an maximum average output power of 249 mW was obtained at 13 kHz. The pulse width maintained 3.4-3.5 ns from 5 to 20 kHz. The maximum pulse energy of 28.1 µJ was obtained at 5 kHz, and the corresponding peak power was up to 8.1 kW.

5.
Molecules ; 29(11)2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38893439

RESUMEN

Hydrogen peroxide (H2O2) is an environmentally friendly oxidant with a wide range of applications, and the two-electron pathway (2e-) of the oxygen reduction reaction (ORR) for H2O2 production has attracted much attention due to its eco-friendly nature and operational simplicity in contrast to the conventional anthraquinone process. The challenge is to design electrocatalysts with high activity and selectivity and to understand their structure-activity relationship and catalytic mechanism in the ORR process. Covalent organic frameworks (COFs) provide an efficient template for the construction of highly efficient electrocatalysts due to their designable structure, excellent stability, and controllable porosity. This review firstly outlines the design principles of COFs, including the selection of metallic and nonmetallic active sites, the modulation of the electronic structure of the active sites, and the dimensionality modulation of the COFs, to provide guidance for improving the production performance of H2O2. Subsequently, representative results are summarized in terms of both metallic and metal-free sites to follow the latest progress. Moreover, the challenges and perspectives of 2e- ORR electrocatalysts based on COFs are discussed.

6.
Front Psychol ; 15: 1281207, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38899122

RESUMEN

Anthropomorphism, the attribution of human-like qualities (e.g., mental states) to nonhuman entities, is a universal but variable psychological experience. Adults with professionally diagnosed autism or high levels of subclinical autistic traits consistently show greater tendencies to anthropomorphize, which has been hypothesized to reflect 1) a compensatory mechanism for lack of social connectedness and 2) a persistence of childhood anthropomorphism into adulthood. Here, we directly tested these hypotheses in a general population sample consisting of both adults (N=685, 17-58 years old) and early adolescents (N=145, 12-14 years old) using the refined 9-item Anthropomorphism Questionnaire (AnthQ9), which measures both present and childhood anthropomorphic tendencies. We found that adults with heightened autistic traits reported increased present anthropomorphism (e.g., tend more to perceive computers as having minds), which held even after controlling for social connectedness. In contrast, adolescents with heightened autistic traits did not show increased present anthropomorphism, but rather reported reduced childhood anthropomorphism (e.g., less likely to perceive toys as having feelings) after controlling for social connectedness. We also found evidence that the present and childhood subscales of the AnthQ9 may tap into fundamentally different aspects of anthropomorphism. The results suggest that increased anthropomorphic tendencies in adults with heightened autistic traits cannot be explained solely by increased sociality motivation, but may be due to delayed development of anthropomorphism, although alternative possibilities of measurement problems cannot be ruled out. Implications for the measurement of anthropomorphism and its relation with theory of mind were also discussed.

7.
Nat Microbiol ; 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38862603

RESUMEN

Dimethylsulfoniopropionate (DMSP) is an abundant marine organosulfur compound with roles in stress protection, chemotaxis, nutrient and sulfur cycling and climate regulation. Here we report the discovery of a bifunctional DMSP biosynthesis enzyme, DsyGD, in the transamination pathway of the rhizobacterium Gynuella sunshinyii and some filamentous cyanobacteria not previously known to produce DMSP. DsyGD produces DMSP through its N-terminal DsyG methylthiohydroxybutyrate S-methyltransferase and C-terminal DsyD dimethylsulfoniohydroxybutyrate decarboxylase domains. Phylogenetically distinct DsyG-like proteins, termed DSYE, with methylthiohydroxybutyrate S-methyltransferase activity were found in diverse and environmentally abundant algae, comprising a mix of low, high and previously unknown DMSP producers. Algae containing DSYE, particularly bloom-forming Pelagophyceae species, were globally more abundant DMSP producers than those with previously described DMSP synthesis genes. This work greatly increases the number and diversity of predicted DMSP-producing organisms and highlights the importance of Pelagophyceae and other DSYE-containing algae in global DMSP production and sulfur cycling.

8.
Arab J Gastroenterol ; 25(2): 150-159, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38719664

RESUMEN

BACKGROUND AND STUDY AIMS: The prognosis of colorectal cancer (CRC) is related to natural killer (NK) cells, but the molecular subtype features of CRC based on NK cells are still unknown. This study aimed to identify NK cell-related molecular subtypes of CRC and analyze the survival status and immune landscape of patients with different subtypes. PATIENTS/MATERIAL AND METHODS: mRNA expression data, single nucleotide variant (SNV) data, and clinical information of CRC patients were obtained from The Cancer Genome Atlas. Differentially expressed genes (DEGs) were obtained through differential analysis, and the intersection was taken with NK cell-associated genes to obtain 103 NK cell-associated CRC DEGs (NCDEGs). Based on NCDEGs, CRC samples were divided into three clusters through unsupervised clustering analysis. Survival analysis, immune analysis, Gene Set Enrichment Analysis (GSEA), and tumor mutation burden (TMB) analysis were performed. Finally, NCDEG-related small-molecule drugs were screened using the CMap database. RESULTS: Survival analysis revealed that cluster2 had a lower survival rate than cluster1 and cluster3 (p < 0.05). Immune infiltration analysis found that the immune infiltration levels and immune checkpoint expression levels of cluster1_3 were substantially higher than those of cluster2, and the tumor purity was the opposite (p < 0.05). GSEA presented that cluster1_3 was significantly enriched in the chemokine signaling pathway, ECM receptor interaction, and antigen processing and presentation pathways (p < 0.05). The TMB of cluster1_3 was significantly higher than that of cluster2 (p < 0.05). Genes with the highest mutation rate in CRC were APC, TP53, TTN, and KRAS. Drug prediction results showed that small-molecule drugs that reverse the upregulation of NCDEGs, deoxycholic acid, dipivefrine, phenformin, and other drugs may improve the prognosis of CRC. CONCLUSION: NK cell-associated CRC subtypes can be used to evaluate the tumor characteristics of CRC patients and provide an important reference for CRC patients.


Asunto(s)
Neoplasias Colorrectales , Células Asesinas Naturales , Humanos , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/inmunología , Neoplasias Colorrectales/patología , Células Asesinas Naturales/inmunología , Pronóstico , Mutación , Tasa de Supervivencia , Análisis de Supervivencia , Regulación Neoplásica de la Expresión Génica , Femenino , Masculino , Perfilación de la Expresión Génica/métodos
9.
J Agric Food Chem ; 72(21): 12029-12044, 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38752706

RESUMEN

Weeds present a significant challenge to agricultural productivity, and acetyl-CoA carboxylase (ACCase)-inhibiting herbicides have proven to be effective in managing weed populations in rice fields. To develop ACCase-inhibiting herbicide-resistant rice, we generated mutants of rice ACCase (OsACC) featuring Ile-1792-Leu or Gly-2107-Ser substitutions through ethyl methyl sulfonate (EMS) mutagenesis. The Ile-1792-Leu mutant displayed cross-resistance to aryloxyphenoxypropionate (APP) and phenylpyrazoline (DEN) herbicides, whereas the Gly-2107-Ser mutants primarily exhibited cross-resistance to APP herbicides with diminished resistance to the DEN herbicide. In vitro assays of the OsACC activity revealed an increase in resistance to haloxyfop and quizalofop, ranging from 4.84- to 29-fold in the mutants compared to that in wild-type. Structural modeling revealed that both mutations likely reduce the binding affinity between OsACC and ACCase inhibitors, thereby imparting resistance. This study offers insights into two target-site mutations, contributing to the breeding of herbicide-resistant rice and presenting alternative weed management strategies in rice cultivation.


Asunto(s)
Acetil-CoA Carboxilasa , Inhibidores Enzimáticos , Resistencia a los Herbicidas , Herbicidas , Mutación , Oryza , Proteínas de Plantas , Acetil-CoA Carboxilasa/genética , Acetil-CoA Carboxilasa/antagonistas & inhibidores , Acetil-CoA Carboxilasa/metabolismo , Acetil-CoA Carboxilasa/química , Oryza/genética , Oryza/enzimología , Herbicidas/farmacología , Herbicidas/química , Resistencia a los Herbicidas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/química , Proteínas de Plantas/antagonistas & inhibidores , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Malezas/efectos de los fármacos , Malezas/genética , Malezas/enzimología
10.
Front Pharmacol ; 15: 1374182, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38783959

RESUMEN

Lung cancer has high metastasis and drug resistance. The prognosis of lung cancer patients is poor and the patients' survival chances are easily neglected. Ferroptosis is a programmed cell death proposed in 2012, which differs from apoptosis, necrosis and autophagy. Ferroptosis is a novel type of regulated cell death which is driven by iron-dependent lipid peroxidation and subsequent plasma membrane ruptures. It has broad prospects in the field of tumor disease treatment. At present, multiple studies have shown that biological compounds can induce ferroptosis in lung cancer cells, which exhibits significant anti-cancer effects, and they have the advantages in high safety, minimal side effects, and less possibility to drug resistance. In this review, we summarize the biological compounds used for the treatment of lung cancer by focusing on ferroptosis and its mechanism. In addition, we systematically review the current research status of combining nanotechnology with biological compounds for tumor treatment, shed new light for targeting ferroptosis pathways and applying biological compounds-based therapies.

11.
Mar Pollut Bull ; 202: 116258, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38493606

RESUMEN

Arsenic (As) is an abundant metalloid in marine environments, while the biogeochemical cycling of As in cold seeps remains poorly understood. We characterized the speciation of As and investigated controls of As distribution in cold seeps of South China Sea. High methane concentrations (0.2-5.5 mmol/L) and rapid sulfate depletion were observed in the seepage. Dissolved inorganic arsenic (DIAs) was enriched in the porewater ranging from 7.5 to 23.5 µg/L. As in the solid phase ranged from 2.9 to 22.6 µg/g, and sulfide mineral-bound As dominated the total arsenic (TAs) pool, followed by iron (manganese, aluminum) oxide-bound As. The significant correlations between porewater Fe2+ and DIAs reflect the controls of iron on DIAs release. Incubation experiments showed that adsorption to the solid phase and sulfate reduction activity affected the bioavailability and removal of DIAs, suggesting that multiple processes regulate the speciation and transformation of As in seep sediments.


Asunto(s)
Arsénico , Monitoreo del Ambiente , Sedimentos Geológicos , Contaminantes Químicos del Agua , Sedimentos Geológicos/química , Arsénico/análisis , Contaminantes Químicos del Agua/análisis , China , Agua de Mar/química
12.
Data Brief ; 53: 110183, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38406249

RESUMEN

DNA-dependent protein kinase catalytic subunit (DNA-PK) is a multifunctional serine­threonine protein kinase that plays roles in non-homologous end joining of DNA repair in cells. NU7441 is a specific DNA-PKcs inhibitor. We investigated the effects of NU7441 on the transcriptome of BT549 triple negative breast cancer cells. Total RNA extracted from NU7441-treated or control BT549 cells was processed for preparation of sequencing libraries. Assessment of read quality was performed using fastqc tool. Trimming and filtering low-quality reads were performed using fastp. Reads were aligned by hisat2. SAM files were converted to BAM files using Samtools. The gene differential expression analysis, Gene Ontology (GO) analysis and KEGG pathway analysis were performed. After NU7441 treatment, total number of 2045 differential genes were selected according to |log2(FoldChange)| >= 1 & padj<= 0.05, among which 1365 genes were down-regulated and 680 genes were up-regulated. The differential expression genes in pattern recognition receptors (PRRs) immune responses signals, including NOD-like receptor signaling, Toll-like receptor signaling, RIG-I-like receptor signaling and cytosolic DNA-sensing pathways were noted in this paper.

13.
Br J Dermatol ; 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38366639

RESUMEN

BACKGROUND: Xeligekimab is a fully human monoclonal antibody that selectively neutralizes IL-17A and had shown potential efficacy in preliminary trials. OBJECTIVE: To evaluate the efficacy and safety of Xeligekimab in Chinese patients with moderate-to-severe psoriasis. METHODS: A total of 420 Chinese patients were randomized to 200 mg Xeligekimab every 2 weeks (n = 281) or placebo (n = 139) for the first 12 weeks, followed by extending the treatment schedule to GR1501 every 4 weeks for further 40 weeks. Efficacy was assessed by evaluating the Physician's Global Assessment (PGA) 0/1 and Psoriasis Area and Severity Index (PASI) 75/90/100 improvement. The safety profile was also evaluated. RESULTS: At week 12, The PASI 75/90/100 were achieved in 90.7%/74.4%/30.2%% patients in GR1501 group compared with 8.6%/1.4%/0% patients in placebo group, respectively. The PGA 0/1 were achieved in 74.4% patients of GR1501 group and 3.6% patients in placebo group, respectively. The PASI 75 and PGA 0/1 maintained until week 52. No unexpected adverse events were observed. CONCLUSION: Xeligekimab showed high efficacy and is well tolerated in Chinese patients with moderate-to-severe plaque psoriasis.

14.
Carbohydr Polym ; 330: 121829, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38368108

RESUMEN

The herbal medicine Polygonatum cyrtonema is highly regarded in China for its medicinal and dietary properties. However, further research is needed to elucidate the structure of its polysaccharide and understand how it promotes human health by modulating the gut microbiota. This study aims to investigate a homogeneous polysaccharide (PCP95-1-1) from Polygonatum cyrtonema and assess its susceptibility to digestion as well as its utilization by intestinal microbiota. The results confirmed that PCP95-1-1 is an agavin-type fructan, which possesses two fructose chains, namely ß-(2 â†’ 6) and ß-(2 â†’ 1) fructosyl-fructose, attached to the sucrose core, and has branches of ß-D-Fruf residues. Moreover, PCP95-1-1 demonstrated resistance to digestion and maintained its reducing sugar content throughout the digestive system, indicating it could reach the gut without being digested. In vitro fermentation of PCP95-1-1 significantly decreased the pH value (p < 0.05) while notably increasing the production of short-chain fatty acids (SCFAs), confirming its utilization by human gut microbiota. Additionally, PCP95-1-1 exhibited a significant ability (p < 0.05) to beneficial bacteria such as Megamonas and Bifidobacterium, while reducing the presence of facultative or conditional pathogens such as Escherichia-Shigella and Klebsiella at the genus level. Consequently, PCP95-1-1 has the potential to positively influence physical well-being by modulating the gut microbiota environment and can be developed as a functional food.


Asunto(s)
Microbioma Gastrointestinal , Polygonatum , Humanos , Fructanos/farmacología , Polygonatum/química , Polisacáridos , Fructosa
15.
Front Behav Neurosci ; 18: 1332760, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38333761

RESUMEN

Pain, a universal and burdensome condition, influences numerous individuals worldwide. It encompasses sensory, emotional, and cognitive facets, with recent research placing a heightened emphasis on comprehending pain's impact on emotion and cognition. Cognitive bias, which encompasses attentional bias, interpretation bias, and memory bias, signifies the presence of cognitive distortions influenced by emotional factors. It has gained significant prominence in pain-related research. Human studies have shown that individuals experiencing pain exhibit cognitive bias. Similarly, animal studies have demonstrated cognitive bias in pain-induced states across various species and disease models. In this study, we aimed to investigate the memory bias displayed by rats experiencing acute pain, using the affective bias test (ABT) as a tool and administering either hotplate or formalin to induce acute pain. Our data showed that rats demonstrated a significant preference for the control treatment-related substrate over the substrate associated with formalin treatment (p < 0.001), an indication of the prominent memory bias stimulated by acute formalin injections. However, when exposed to substrates related to hotplate treatment and control treatment, the acute pain induced by the hotplate treatment failed to generate a statistically significant choice bias in rats (p = 0.674). Our study demonstrates that the negative emotions associated with acute pain can be reflected by memory bias in ABT, at least for formalin-induced acute pain. This finding will augment our comprehension of the emotional and cognitive aspects of acute pain.

16.
Neural Netw ; 172: 106113, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38232430

RESUMEN

In the domain of graph-structured data learning, semi-supervised node classification serves as a critical task, relying mainly on the information from unlabeled nodes and a minor fraction of labeled nodes for training. However, real-world graph-structured data often suffer from label noise, which significantly undermines the performance of Graph Neural Networks (GNNs). This problem becomes increasingly severe in situations where labels are scarce. To tackle this issue of sparse and noisy labels, we propose a novel approach Contrastive Robust Graph Neural Network (CR-GNN), Firstly, considering label sparsity and noise, we employ unsupervised contrastive loss and further incorporate homophily in the graph structure, thus introducing neighbor contrastive loss. Moreover, data augmentation is typically used to construct positive and negative samples in contrastive learning, which may result in inconsistent prediction outcomes. Based on this, we propose a dynamic cross-entropy loss, which selects the nodes with consistent predictions as reliable nodes for cross-entropy loss and benefits to mitigate the overfitting to labeling noise. Finally, we propose cross-space consistency to narrow the semantic gap between the contrast and classification spaces. Extensive experiments on multiple publicly available datasets demonstrate that CR-GNN notably outperforms existing methods in resisting label noise.


Asunto(s)
Aprendizaje , Redes Neurales de la Computación , Entropía , Semántica
17.
J Agric Food Chem ; 72(8): 4277-4291, 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38288993

RESUMEN

Salt stress significantly impedes plant growth and the crop yield. This study utilized de novo transcriptome assembly and ribosome profiling to explore mRNA translation's role in rice salt tolerance. We identified unrecognized translated open reading frames (ORFs), including 42 upstream transcripts and 86 unannotated transcripts. A noteworthy discovery was the role of a small ORF, Ospep5, in conferring salt tolerance. Overexpression of Ospep5 in plants increased salt tolerance, while its absence led to heightened sensitivity. This hypothesis was corroborated by the findings that exogenous application of the synthetic small peptide Ospep5 bolstered salt tolerance in both rice and Arabidopsis. We found that the mechanism underpinning the Ospep5-mediated salt tolerance involves the maintenance of intracellular Na+/K+ homeostasis, facilitated by upregulation of high-affinity potassium transporters (HKT) and Na+/H+ exchangers (SOS1). Furthermore, a comprehensive multiomics approach, particularly ribosome profiling, is instrumental in uncovering unannotated ORFs and elucidating their functions in plant stress responses.


Asunto(s)
Arabidopsis , Oryza , Estrés Salino , Tolerancia a la Sal/genética , Perfilación de la Expresión Génica , Sodio/metabolismo , Plantas Tolerantes a la Sal/metabolismo , Transcriptoma , Intercambiadores de Sodio-Hidrógeno/genética , Intercambiadores de Sodio-Hidrógeno/metabolismo , Arabidopsis/metabolismo , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Oryza/metabolismo
18.
Cancer Lett ; 587: 216622, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38246224

RESUMEN

Triptolide, a natural bioactive compound derived from herbal medicine Tripterygium wilfordii, has multiple biological activities including anti-cancer effect, which is being tested in clinical trials for treating cancers. However, the exact mechanism by which Triptolide exerts its cytotoxic effects, particularly its specific protein targets, remains unclear. Here, we show that Triptolide effectively induces cytotoxicity in gastric cancer cells by increasing reactive oxygen species (ROS) levels. Further investigations reveal that ROS accumulation contributes to the induction of Endoplasmic Reticulum (ER) stress, and subsequently autophagy induction in response to Triptolide. Meanwhile, this autophagy is cytoprotective. Interestingly, through activity-based protein profiling (ABPP) approach, we identify peroxiredoxins-2 (PRDX2), a component of the key enzyme systems that act in the defense against oxidative stress and protect cells against hydroperoxides, as direct binding target of Triptolide. By covalently binding to PRDX2 to inhibit its antioxidant activity, Triptolide increases ROS levels. Moreover, overexpression of PRDX2 inhibits and knockdown of the expression of PRDX2 increases Triptolide-induced apoptosis. Collectively, these results indicate PRDX2 as a direct target of Triptolides for inducing apoptosis. Our results not only provide novel insight into the underlying mechanisms of Triptolide-induced cytotoxic effects, but also indicate PRDX2 as a promising potential therapeutic target for developing anti-gastric cancer agents.


Asunto(s)
Diterpenos , Fenantrenos , Neoplasias Gástricas , Humanos , Especies Reactivas de Oxígeno/metabolismo , Neoplasias Gástricas/tratamiento farmacológico , Peroxirredoxinas/genética , Diterpenos/farmacología , Fenantrenos/farmacología , Autofagia , Apoptosis , Compuestos Epoxi/farmacología
19.
Chin Med J (Engl) ; 137(2): 200-208, 2024 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-37482623

RESUMEN

BACKGROUND: Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD. METHODS: This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied. RESULTS: At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs . placebo, 95% CI 31%-69%) and 45% (low vs . placebo, 95% CI 26%-64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator's Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310. CONCLUSION: CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.


Asunto(s)
Dermatitis Atópica , Adulto , Humanos , Dermatitis Atópica/tratamiento farmacológico , Resultado del Tratamiento , Índice de Severidad de la Enfermedad , Anticuerpos Monoclonales Humanizados/uso terapéutico , Inyecciones Subcutáneas , Método Doble Ciego
20.
World J Pediatr ; 20(3): 250-258, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38070095

RESUMEN

BACKGROUND: Surgery plays an important role in the treatment of neuroblastoma. Perioperative complications may impact the course of neuroblastoma treatment. To date, comprehensive analyses of complications and risk factors have been lacking. METHODS: Patients with retroperitoneal neuroblastoma undergoing tumor resection were retrospectively analyzed between 2014 and 2021. The data collected included clinical characteristics, operative details, operative complications and postoperative outcomes. Risk factors for perioperative complications of retroperitoneal neuroblastoma were analyzed. RESULTS: A total of 571 patients were enrolled in this study. Perioperative complications were observed in 255 (44.7%) patients. Lymphatic leakage (28.4%), diarrhea (13.5%), and injury (vascular, nerve and organ; 7.5%) were the most frequent complications. There were three operation-related deaths (0.53%): massive hemorrhage (n = 1), biliary tract perforation (n = 1) and intestinal necrosis (n = 1). The presence of image-defined risk factors (IDRFs) [odds ratio (OR) = 2.09, P < 0.01], high stage of the International Neuroblastoma Risk Group staging system (INRGSS) (OR = 0.454, P = 0.04), retroperitoneal lymph node metastasis (OR = 2.433, P = 0.026), superior mesenteric artery encasement (OR = 3.346, P = 0.003), and inferior mesenteric artery encasement (OR = 2.218, P = 0.019) were identified as independent risk factors for perioperative complications. CONCLUSIONS: Despite the high incidence of perioperative complications, the associated mortality rate was quite low. Perioperative complications of retroperitoneal neuroblastoma were associated with IDRFs, INRGSS, retroperitoneal lymph node metastasis and vascular encasement. Patients with high-risk factors should receive more serious attention during surgery but should not discourage the determination to pursue total resection of neuroblastoma. Video Abstract (MP4 94289 KB).


Asunto(s)
Neuroblastoma , Niño , Humanos , Estudios Retrospectivos , Incidencia , Metástasis Linfática , Neuroblastoma/epidemiología , Neuroblastoma/cirugía , Factores de Riesgo , Complicaciones Posoperatorias/epidemiología , Estadificación de Neoplasias
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