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1.
PeerJ ; 12: e17586, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38974413

RESUMEN

The development of floral organs, crucial for the establishment of floral symmetry and morphology in higher plants, is regulated by MADS-box genes. In sunflower, the capitulum is comprised of ray and disc florets with various floral organs. In the sunflower long petal mutant (lpm), the abnormal disc (ray-like) floret possesses prolongated petals and degenerated stamens, resulting in a transformation from zygomorphic to actinomorphic symmetry. In this study, we investigated the effect of MADS-box genes on floral organs, particularly on petals, using WT and lpm plants as materials. Based on our RNA-seq data, 29 MADS-box candidate genes were identified, and their roles on floral organ development, especially in petals, were explored, by analyzing the expression levels in various tissues in WT and lpm plants through RNA-sequencing and qPCR. The results suggested that HaMADS3, HaMADS7, and HaMADS8 could regulate petal development in sunflower. High levels of HaMADS3 that relieved the inhibition of cell proliferation, together with low levels of HaMADS7 and HaMADS8, promoted petal prolongation and maintained the morphology of ray florets. In contrast, low levels of HaMADS3 and high levels of HaMADS7 and HaMADS8 repressed petal extension and maintained the morphology of disc florets. Their coordination may contribute to the differentiation of disc and ray florets in sunflower and maintain the balance between attracting pollinators and producing offspring. Meanwhile, Pearson correlation analysis between petal length and expression levels of MADS-box genes further indicated their involvement in petal prolongation. Additionally, the analysis of cis-acting elements indicated that these three MADS-box genes may regulate petal development and floral symmetry establishment by regulating the expression activity of HaCYC2c. Our findings can provide some new understanding of the molecular regulatory network of petal development and floral morphology formation, as well as the differentiation of disc and ray florets in sunflower.


Asunto(s)
Flores , Regulación de la Expresión Génica de las Plantas , Helianthus , Proteínas de Dominio MADS , Proteínas de Plantas , Helianthus/genética , Helianthus/crecimiento & desarrollo , Helianthus/metabolismo , Flores/genética , Flores/crecimiento & desarrollo , Proteínas de Dominio MADS/genética , Proteínas de Dominio MADS/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
2.
J Orthop Translat ; 46: 116-128, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38867741

RESUMEN

Objectives: SPARCL1 is a matricellular protein that mediates the cell-matrix interactions and participates in physiological processes such as cell adhesion, differentiation and proliferation. However, its role in chondrocyte and osteoarthritis (OA) progression has not been fully characterized. We aimed to evaluate the effects of SPARCL1 on OA through in vitro and in vivo experiments. Methods: Expression of SPARCL1 was examined in 55 paired human OA samples. Effects of Sparcl1 on chondrocytes were identified in vitro. Intra-articular injection was performed in an anterior cruciate ligament transection (ACLT) mouse model. Alterations of SPARCL1-mediated signaling pathway were identified by RNA-seq analysis. qPCR and western-blot were used to demonstrate the potential signaling pathway. Results: SPARCL1 expression in the OA cartilage was increased compared with undamaged cartilage. Recombinant Sparcl1 protein induced extracellular matrix degradation in chondrocytes. Furthermore, intra-articular injection of recombinant Sparcl1 protein in ACLT mice could promote OA pathogenesis. Mechanistically, Sparcl1 activated TNF/NF-κB pathway and consequently led to increased transcription of inflammatory factors and catabolism genes of cartilage, which could be reversed by NF-κB inhibitor BAY 11-7082. Conclusion: SPARCL1 could promote extracellular matrix degradation and inflammatory response to accelerate OA progression via TNF/NF-κB pathway. The translational potential of this article: The current research could help to gain further insights into the underlying molecular mechanism in OA development, and provides a biological rationale for the use of SPARCL1 as a potential therapeutic target of OA.

3.
bioRxiv ; 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38915509

RESUMEN

Underlying drivers of late-onset Alzheimer's disease (LOAD) pathology remain unknown. However, multiple biologically diverse risk factors share a common pathological progression. To identify convergent molecular abnormalities that drive LOAD pathogenesis we compared two common midlife risk factors for LOAD, heavy alcohol use and obesity. This revealed that disrupted lipophagy is an underlying cause of LOAD pathogenesis. Both exposures reduced lysosomal flux, with a loss of neuronal lysosomal acid lipase (LAL). This resulted in neuronal lysosomal lipid (NLL) accumulation, which opposed Aß localization to lysosomes. Neuronal LAL loss both preceded (with aging) and promoted (targeted knockdown) Aß pathology and cognitive deficits in AD mice. The addition of recombinant LAL ex vivo and neuronal LAL overexpression in vivo prevented amyloid increases and improved cognition. In WT mice, neuronal LAL declined with aging and correlated negatively with entorhinal Aß. In healthy human brain, LAL also declined with age, suggesting this contributes to the age-related vulnerability for AD. In human LOAD LAL was further reduced, correlated negatively with Aß1-42, and occurred with polymerase pausing at the LAL gene. Together, this finds that the loss of neuronal LAL promotes NLL accumulation to impede degradation of Aß in neuronal lysosomes to drive AD amyloid pathology.

4.
bioRxiv ; 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38915481

RESUMEN

Motivation: Biomarker detection plays a pivotal role in biomedical research. Integrating omics studies from multiple cohorts can enhance statistical power, accuracy and robustness of the detection results. However, existing methods for horizontally combining omics studies are mostly designed for two-class scenarios (e.g., cases versus controls) and are not directly applicable for studies with multi-class design (e.g., samples from multiple disease subtypes, treatments, tissues, or cell types). Results: We propose a statistical framework, namely Mutual Information Concordance Analysis (MICA), to detect biomarkers with concordant multi-class expression pattern across multiple omics studies from an information theoretic perspective. Our approach first detects biomarkers with concordant multi-class patterns across partial or all of the omics studies using a global test by mutual information. A post hoc analysis is then performed for each detected biomarkers and identify studies with concordant pattern. Extensive simulations demonstrate improved accuracy and successful false discovery rate control of MICA compared to an existing MCC method. The method is then applied to two practical scenarios: four tissues of mouse metabolism-related transcriptomic studies, and three sources of estrogen treatment expression profiles. Detected biomarkers by MICA show intriguing biological insights and functional annotations. Additionally, we implemented MICA for single-cell RNA-Seq data for tumor progression biomarkers, highlighting critical roles of ribosomal function in the tumor microenvironment of triple-negative breast cancer and underscoring the potential of MICA for detecting novel therapeutic targets. Availability: https://github.com/jianzou75/MICA.

5.
Cancer Manag Res ; 16: 593-602, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38855331

RESUMEN

Background: Regorafenib, a novel multikinase inhibitor, has been approved by the US Food and Drug Administration as a standard treatment choice for metastatic colorectal cancer (mCRC). Nonetheless, its substantial cost places a significant burden on social health resources and patients. However, the cost-effectiveness (CE) of regorafenib compared to other third-line therapies is still undetermined. Objective: This study aims to assess the CE of regorafenib compared to other third-line therapies for the treatment of mCRC. Methods: We conducted a comprehensive literature search in PubMed, Medline, Scopus, Embase, Cochrane Library, as well as nine other databases to identify relevant studies published up to October 2023, focusing on patients with mCRC and examining the cost-effectiveness of regorafenib. Following the screening and extraction of pertinent data, the study quality was assessed using the Quality of Health Economic Studies (QHES) checklist. Results: The literature search yielded 751 records, and after applying the inclusion criteria, 13 studies from 7 different countries were included. Of these, 7 studies evaluated the cost-effectiveness of regorafenib compared to trifluridine/tipiracil (TAS-102), 3 studies compared regorafenib with best supportive care (BSC), and 3 studies compared regorafenib with fruquintinib, serplulimab, and regorafenib dose optimization (ReDo).The quality of the included studies was high with an average QHES scores of 85.62. Regorafenib standard dose proves to be less cost-effective than alternative third-line therapies. Implementing a dose optimization strategy could potentially rectify this disparity and enhance the cost-effectiveness of regorafenib. Conclusion: The use of the standard dose of regorafenib is generally regarded as not cost-effective when compared to other third-line therapies for patients with mCRC. However, implementing a dose-escalation strategy may enhance regorafenib's cost-effectiveness. Consequently, significant price reductions or optimizing the dose of regorafenib are required to achieve cost-effectiveness.

6.
Huan Jing Ke Xue ; 45(6): 3725-3733, 2024 Jun 08.
Artículo en Chino | MEDLINE | ID: mdl-38897792

RESUMEN

Organic fertilizer substitution has been promoted as a weight loss, efficient, and diversified fertilizer substitution technology in agricultural production. However, there is a lack of comprehensive assessment of the impact of organic fertilizers on N2O and NO emissions from orchards. In this study, N2O and NO emissions from peach orchards were observed annually using static dark box-gas chromatography to compare the effects of chemical fertilizer application alone and partial replacement of chemical fertilizer treatment on NO emissions from peach orchards. The results showed that the partial replacement of chemical fertilizers with organic fertilizers reduced the total N2O and NO emissions from peach orchards by 15.0 % and 9.4 %, respectively. The N2O and NO emission factors were reduced by 21.3 % and 21.1 %. The mineral N content of the soil in the organic fertilizer treatment was lower than that in the chemical fertilizer treatment alone. The organic fertilizer treatment increased the contribution of AOA to nitrification and decreased the contribution of AOB, thus reducing N2O and NO from nitrification. In addition, the results of the dual isotope mixing model[δ18O(N2O/H2O) vs. δ15NSP] indicated that the bacterial denitrification/nitrifying bacterial denitrification (bD/nD) process served as the primary pathway for N2O emissions in peach orchards. Partial substitution with organic fertilizers enhanced soil denitrification, resulting in larger reductions in the amounts of N2O and NO. Therefore, partial substitution of organic fertilizer is a viable measure to mitigate nitrogen oxide emissions from orchards and to achieve green and low-carbon development in agriculture.

7.
Carbohydr Polym ; 339: 122228, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38823903

RESUMEN

Meat products consumption is rising globally, but concerns about sustainability, fat content, and shelf life. Synthetic additives and preservatives used for extending the shelf life of meat often carry health and environmental drawbacks. Seed mucilage, natural polysaccharides, possesses unique functional properties like water holding, emulsifying, and film forming, offering potential alternatives in meat processing and preservation. This study explores the application of seed mucilage from diverse sources (e.g., flaxseed, psyllium, basil) in various meat and meat products processing and preservation. Mucilage's water-holding and emulsifying properties can potentially bind fat and decrease the overall lipid content in meat and meat-based products. Moreover, antimicrobial and film-forming properties of mucilage can potentially inhibit microbial growth and reduce oxidation, extending the shelf life. This review emphasizes the advantages of incorporating mucilage into processing and coating strategies for meat and seafood products.


Asunto(s)
Conservación de Alimentos , Productos de la Carne , Mucílago de Planta , Semillas , Semillas/química , Productos de la Carne/análisis , Mucílago de Planta/química , Conservación de Alimentos/métodos , Lino/química , Biopolímeros/química , Polisacáridos/química , Animales , Psyllium/química , Manipulación de Alimentos/métodos
8.
Sheng Li Xue Bao ; 76(3): 407-417, 2024 Jun 25.
Artículo en Chino | MEDLINE | ID: mdl-38939935

RESUMEN

Noise, as an unavoidable stress (pressure) source in the modern life, affects animals in many ways, both behaviorally and physiologically. Behavioral changes may be driven by changes in hormone secretion in animals. When animals face with noise stress, the neuroendocrine systems, mainly the hypothalamic-pituitary-adrenal (HPA) axis, are activated, which promotes the secretion and release of stress hormones, and then leads to a series of behavioral changes. The behavioral changes can be easily observed, but the changes in physiological indicators such as hormone levels need to be accurately measured. Currently, many studies have measured the variations of stress hormone levels in animals under different noise conditions. Taking glucocorticoid as an example, this paper summarizes the different measurement methods of stress hormones, especially the non-invasive measurement methods, and compares the advantages and shortcomings of them. It provides a variety of measurement choices for the study of related issues, and also helps us to further understand the sources of animal stress, in order to provide a better habitat for animals.


Asunto(s)
Sistema Hipotálamo-Hipofisario , Ruido , Sistema Hipófiso-Suprarrenal , Estrés Fisiológico , Animales , Sistema Hipotálamo-Hipofisario/fisiología , Sistema Hipófiso-Suprarrenal/fisiología , Estrés Fisiológico/fisiología , Glucocorticoides/metabolismo , Estrés Psicológico/fisiopatología
9.
Mol Biotechnol ; 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38780825

RESUMEN

Osteoporosis is a common chronic bone metabolism disorder characterized by decreased bone mass and reduced bone density in the bone tissue. Osteoporosis can lead to increased fragility of the skeleton, making it prone to brittle fractures. Osteoclasts are macrophage-like cells derived from hematopoietic stem cells, and their excessive activity in bone resorption leads to lower bone formation than absorption during bone remodeling, which is one of the important factors inducing osteoporosis. Therefore, how to inhibit osteoclast formation and reducing bone loss is an important direction for treating osteoporosis. Sophoraflavanone G, derived from Sophora flavescens Alt and Rhizoma Drynariae, is a flavonoid compound with various biological activities. However, there have been few studies on osteoporosis and osteoclasts so far. Therefore, we hypothesize that genistein G can inhibit osteoclast differentiation, alleviate bone loss phenomenon, and conduct in vitro and in vivo experiments for research and verification purposes.

10.
Nat Prod Res ; : 1-7, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38771014

RESUMEN

An undescribed dammarane triterpenoid saponin Cypaliuruside F was isolated from the leaves of Cyclocarya paliurus in our preliminary study. The MTT assay, flow cytometry, cell scratch, and DAPI staining were used to detect the antitumor effects of Cypaliuruside F on HepG2 cells. Subsequently, network pharmacology and molecular docking analysis were used to analyse the key targets of Cypaliuruside F against HCC. In addition, a Western blot was performed to determine the effects of Cypaliuruside F on the expression of key proteins in HepG2 cells. The experimental results indicated that the damarane triterpenoid saponin Cypaliuruside F from Cyclocarya paliurus inhibits the proliferation of HepG2 cells by inducing apoptosis and cell cycle arrest. These changes may promote the apoptosis of HepG2 cells by inhibiting the expression of mTOR, STAT3, and Bcl-2 while activating Bax.

11.
Transl Cancer Res ; 13(4): 1876-1886, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38737678

RESUMEN

Background: Among human papillomavirus (HPV) type, HPV16 displays the strongest carcinogenic capacity for cervical cancer, but the mechanism underlying this phenomenon remains unclear. We investigated the effect and the underlying mechanism of HPV16 on higher carcinogenic capacity than HPV58. Methods: We collected 4,030 cervical exfoliated cell samples for genotyping HPV using HybriBio's proprietary flow-through hybridization technique, liquid-based cytology (LBC), colposcopy, and biopsies if indicated. Four plasmids containing E6 and E7 of HPV16 and 58 were constructed and transfected into 293T and U2OS cells. We detected the cell phenotype using Cell Counting Kit 8 (CCK8) assay, Transwell assay, flow cytometry, and apoptosis assay; the expression of retinoblastoma protein (Rb) and phosphorylated Rb (pRb) was determined via Western blot; and the cell activity was determined via a zebrafish model treated with or without roscovitine. Results: The positive rates of HPV16 and 58 were, respectively, 18.9% and 19.7% in the ≤ low-grade squamous intraepithelial lesion (LSIL) group, 49.5% and 19.6% (P<0.001) in the high-grade squamous intraepithelial lesion (HSIL) group, 65.3% and 9.0% (P<0.001) in the cancer group. In vitro, both 293T and U2OS cells with overexpressed HPV16 E6 and E7 displayed significantly higher cell proliferation, faster cell invasion, decreased cell apoptosis, and accelerated cell cycle from G1 phase to S phase compared to those with overexpressed HPV58 E6 and E7 (all P values <0.05). Rb loss of function was observed in cells with HPV16 E7 overexpression, while a greater level of phosphorylated Rb was observed in cells with HPV58 E7 overexpression. Roscovitine restored Rb expression and decreased the cell activity in zebrafish. Conclusions: HPV16 possesses a stronger carcinogenic ability than does HPV 58, and the mechanism underlying this effect may be the impairment of the E7-Rb pathway.

12.
Front Immunol ; 15: 1358114, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38711518

RESUMEN

Background: The relationship between serum antinuclear antibody (ANA) and rheumatoid arthritis (RA) remains unknown. Therefore, we aimed to evaluate whether serum ANA was associated with an increased risk of RA in a case-control study. Methods: Patients with rheumatoid arthritis hospitalized at Shandong Provincial Hospital from January 2018 to December 2022 were recruited as the case group, and patients with other types of arthritis and healthy people at the same time were taken as the control group. Antinuclear antibody (ANA) was detected by indirect immunofluorescence assays. Propensity score matching was employed to construct a cohort of patients exhibiting comparable baseline characteristics. The relationship between serum ANA and the risk of rheumatoid arthritis was analyzed by logistic regression analysis. Results: A total of 1,175 patients with RA and 1,662 control subjects were included in this study. After adjusting for potential confounding factors in the propensity-score matched cohort, the risk of RA gradually increased with rising of ANA titers. When ANA titers were divided into three groups (1:100, 1:320, and 1:1,000), the OR (95% CI) for ANA titers from low to high was 3.95 (3.01, 5.18), 16.63 (9.44, 29.30), and 17.34 (9.53, 31.54), respectively, compared to those when ANA was negative. The ANA patterns closely related to the occurrence of RA include nuclear homogeneous, nuclear speckled, and cytoplasmic speckled. Among them, the positive rate of nuclear homogeneous was the highest, which accounted for 42.64%. The OR (95% CI) of ANA patterns including nuclear homogeneous, nuclear speckled, and cytoplasmic speckled was 16.81 (11.46, 24.65), 3.40 (2.49, 4.63), and 3.09 (1.77, 5.40), respectively. Conclusion: There was a curve relation between ANA titer and RA, and the higher the ANA titer, the higher the probability of RA. However, there was no statistical difference in probability of RA for 1:320 versus 1:1,000 ANA titers. The most important kind of ANA pattern in the blood of RA patients was nuclear homogeneous. These findings suggest that ANA may be a novel risk marker for RA.


Asunto(s)
Anticuerpos Antinucleares , Artritis Reumatoide , Humanos , Artritis Reumatoide/sangre , Artritis Reumatoide/inmunología , Artritis Reumatoide/diagnóstico , Anticuerpos Antinucleares/sangre , Anticuerpos Antinucleares/inmunología , Masculino , Femenino , Persona de Mediana Edad , Estudios de Casos y Controles , Adulto , Anciano , Biomarcadores/sangre , Factores de Riesgo
13.
Front Immunol ; 15: 1411161, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38799437

RESUMEN

Instruction: Hepatitis B virus (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC). Programmed cell death (PCD) is a critical process in suppressing tumor growth, and alterations in PCD-related genes may contribute to the progression of HBV-HCC. This study aims to develop a prognostic model that incorporates genomic and clinical information based on PCD-related genes, providing novel insights into the molecular heterogeneity of HBV-HCC through bioinformatics analysis and experimental validation. Methods: In this study, we analyzed 139 HBV-HCC samples from The Cancer Genome Atlas (TCGA) and validated them with 30 samples from the Gene Expression Omnibus (GEO) database. Various bioinformatics tools, including differential expression analysis, gene set variation analysis, and machine learning algorithms were used for comprehensive analysis of RNA sequencing data from HBV-HCC patients. Furthermore, among the PCD-related genes, we ultimately chose DLAT for further research on tissue chips and patient cohorts. Besides, immunohistochemistry, qRT-PCR and Western blot analysis were conducted. Results: The cluster analysis identified three distinct subgroups of HBV-HCC patients. Among them, Cluster 2 demonstrated significant activation in DNA replication-related pathways and tumor-related processes. Analysis of copy number variations (CNVs) of PCD-related genes also revealed distinct patterns in the three subgroups, which may be associated with differences in pathway activation and survival outcomes. DLAT in tumor tissues of HBV-HCC patients is upregulated. Discussion: Based on the PCD-related genes, we developed a prognostic model that incorporates genomic and clinical information and provided novel insights into the molecular heterogeneity of HBV-HCC. In our study, we emphasized the significance of PCD-related genes, particularly DLAT, which was examined in vitro to explore its potential clinical implications.


Asunto(s)
Carcinoma Hepatocelular , Virus de la Hepatitis B , Neoplasias Hepáticas , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/virología , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/virología , Pronóstico , Virus de la Hepatitis B/genética , Masculino , Femenino , Regulación Neoplásica de la Expresión Génica , Hepatitis B/complicaciones , Hepatitis B/genética , Hepatitis B/virología , Apoptosis/genética , Persona de Mediana Edad , Variaciones en el Número de Copia de ADN , Biología Computacional/métodos , Biomarcadores de Tumor/genética , Perfilación de la Expresión Génica
14.
Viruses ; 16(5)2024 04 26.
Artículo en Inglés | MEDLINE | ID: mdl-38793564

RESUMEN

Porcine reproductive and respiratory syndrome virus (PRRSV) is a pathogen that causes severe abortions in sows and high piglet mortality, resulting in huge economic losses to the pig industry worldwide. The emerging and novel PRRSV isolates are clinically and biologically important, as there are likely recombination and pathogenic differences among PRRSV genomes. Furthermore, the NADC34-like strain has become a major epidemic strain in some parts of China, but the characterization and pathogenicity of the latest strain in Inner Mongolia have not been reported in detail. In this study, an NADC34-like strain (CHNMGKL1-2304) from Tongliao City, Inner Mongolia was successfully isolated and characterized, and confirmed the pathogenicity in pigs. The phylogenetic tree showed that this strain belonged to sublineage 1.5 and had high homology with the strain JS2021NADC34. There is no recombination between CHNMGKL1-2304 and any other domestic strains. Animal experiments show that the CHNMGKL1-2304 strain is moderately virulent to piglets, which show persistent fever, weight loss and high morbidity but no mortality. The presence of PRRSV nucleic acids was detected in both blood, tissues, nasal and fecal swabs. In addition, obvious pathological changes and positive signals were observed in lung, lymph node, liver and spleen tissues when subjected to hematoxylin-eosin (HE) staining and immunohistochemistry (IHC). This report can provide a basis for epidemiological investigations and subsequent studies of PRRSV.


Asunto(s)
Genoma Viral , Filogenia , Síndrome Respiratorio y de la Reproducción Porcina , Virus del Síndrome Respiratorio y Reproductivo Porcino , Animales , Porcinos , Virus del Síndrome Respiratorio y Reproductivo Porcino/genética , Virus del Síndrome Respiratorio y Reproductivo Porcino/patogenicidad , Virus del Síndrome Respiratorio y Reproductivo Porcino/aislamiento & purificación , Virus del Síndrome Respiratorio y Reproductivo Porcino/clasificación , China , Síndrome Respiratorio y de la Reproducción Porcina/virología , Síndrome Respiratorio y de la Reproducción Porcina/patología , Virulencia , Evolución Molecular
15.
Bioact Mater ; 38: 124-136, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38699245

RESUMEN

Adhesion after tendon injury, which can result in limb movement disorders, is a common clinical complication; however, effective treatment methods are lacking. Hyaluronic acid hydrogels are a new biomedical material used to prevent tendon adhesion owing to their good biocompatibility. In addition, potential drugs that inhibit adhesion formation have gradually been discovered. The anti-adhesion effects of a combination of loaded drugs into hydrogels have become an emerging trend. However, current drug delivery systems usually lack specific regulation of drug release, and the effectiveness of drugs for treating tendon adhesions is mostly flawed. In this study, we identified a new drug, imatinib mesylate (IM), that prevents tendon adhesion and explored its related molecular pathways. In addition, we designed a pH-responsive sustained-release hydrogel for delivery. Using the metal-organic framework ZIF-8 as a drug carrier, we achieved controlled drug release to increase the effective drug dose at the peak of adhesion formation to achieve better therapeutic effects. The results showed that IM blocked the formation of peritendon adhesions by inhibiting the PDGFRß/ERK/STAT3/CLDN1 pathway. Furthermore, the hydrogel with ZIF-8 exhibited better physical properties and drug release curves than the hydrogel loaded only with drugs, showing better prevention and treatment effects on tendon adhesion.

16.
Nat Med ; 30(6): 1680-1688, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38740994

RESUMEN

Emotional distress (ED), commonly characterized by symptoms of depression and/or anxiety, is prevalent in patients with cancer. Preclinical studies suggest that ED can impair antitumor immune responses, but few clinical studies have explored its relationship with response to immune checkpoint inhibitors (ICIs). Here we report results from cohort 1 of the prospective observational STRESS-LUNG study, which investigated the association between ED and clinical efficacy of first-line treatment of ICIs in patients with advanced non-small-cell lung cancer. ED was assessed by Patient Health Questionnaire-9 and Generalized Anxiety Disorder 7-item scale. The study included 227 patients with 111 (48.9%) exhibiting ED who presented depression (Patient Health Questionnaire-9 score ≥5) and/or anxiety (Generalized Anxiety Disorder 7-item score ≥5) symptoms at baseline. On the primary endpoint analysis, patients with baseline ED exhibited a significantly shorter median progression-free survival compared with those without ED (7.9 months versus 15.5 months, hazard ratio 1.73, 95% confidence interval 1.23 to 2.43, P = 0.002). On the secondary endpoint analysis, ED was associated with lower objective response rate (46.8% versus 62.1%, odds ratio 0.54, P = 0.022), reduced 2-year overall survival rate of 46.5% versus 64.9% (hazard ratio for death 1.82, 95% confidence interval 1.12 to 2.97, P = 0.016) and detriments in quality of life. The exploratory analysis indicated that the ED group showed elevated blood cortisol levels, which was associated with adverse survival outcomes. This study suggests that there is an association between ED and worse clinical outcomes in patients with advanced non-small-cell lung cancer treated with ICIs, highlighting the potential significance of addressing ED in cancer management. ClinicalTrials.gov registration: NCT05477979 .


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Inhibidores de Puntos de Control Inmunológico , Neoplasias Pulmonares , Distrés Psicológico , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Carcinoma de Pulmón de Células no Pequeñas/patología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Femenino , Masculino , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/inmunología , Persona de Mediana Edad , Anciano , Estudios Prospectivos , Depresión/tratamiento farmacológico , Ansiedad/tratamiento farmacológico , Resultado del Tratamiento , Supervivencia sin Progresión , Adulto , Anciano de 80 o más Años
17.
ACS Cent Sci ; 10(3): 628-636, 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38559293

RESUMEN

Angelica sinensis, commonly known as Dong Quai in Europe and America and as Dang-gui in China, is a medicinal plant widely utilized for the prevention and treatment of osteoporosis. In this study, we report the discovery of a new category of phthalide from Angelica sinensis, namely falcarinphthalides A and B (1 and 2), which contains two fragments, (3R,8S)-falcarindiol (3) and (Z)-ligustilide (4). Falcarinphthalides A and B (1 and 2) represent two unprecedented carbon skeletons of phthalide in natural products, and their antiosteoporotic activities were evaluated. The structures of 1 and 2, including their absolute configurations, were established using extensive analysis of NMR spectra, chemical derivatization, and ECD/VCD calculations. Based on LC-HR-ESI-MS analysis and DFT calculations, a production mechanism for 1 and 2 involving enzyme-catalyzed Diels-Alder/retro-Diels-Alder reactions was proposed. Falcarinphthalide A (1), the most promising lead compound, exhibits potent in vitro antiosteoporotic activity by inhibiting NF-κB and c-Fos signaling-mediated osteoclastogenesis. Moreover, the bioinspired gram-scale total synthesis of 1, guided by intensive DFT study, has paved the way for further biological investigation. The discovery and gram-scale total synthesis of falcarinphthalide A (1) provide a compelling lead compound and a novel molecular scaffold for treating osteoporosis and other metabolic bone diseases.

18.
PLoS One ; 19(4): e0301902, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38603697

RESUMEN

Spectral collinearity and limited spectral datasets are the problems influencing Chemical Oxygen Demand (COD) modeling. To address the first problem and obtain optimal modeling range, the spectra are preprocessed using six methods including Standard Normal Variate, Savitzky-Golay Smoothing Filtering (SG) etc. Subsequently, the 190-350 nm spectral range is divided into 10 subintervals, and Interval Partial Least Squares (IPLS) is used to perform PLS modeling on each interval. The results indicate that it is best modeled in the 7th range (238~253 nm). The values of Mean Square Error (MSE), Mean Absolute Error (MAE) and R2score of the model without pretreatment are 1.6489, 1.0661, and 0.9942. After pretreatment, the SG is better than others, with MSE and MAE decreasing to 1.4727, 1.0318 and R2score improving to 0.9944. Using the optimal model, the predicted COD for three samples are 10.87 mg/L, 14.88 mg/L, and 19.29 mg/L. To address the problem of the small dataset, using Generative Adversarial Networks for data augmentation, three datasets are obtained for Support Vector Machine (SVM) modeling. The results indicate that, compared to the original dataset, the SVM's MSE and MAE have decreased, while its accuracy has improved by 2.88%, 11.53%, and 11.53%, and the R2score has improved by 18.07%, 17.40%, and 18.74%.


Asunto(s)
Espectroscopía Infrarroja Corta , Máquina de Vectores de Soporte , Espectroscopía Infrarroja Corta/métodos , Análisis de la Demanda Biológica de Oxígeno , Análisis de los Mínimos Cuadrados , Agua , Algoritmos
19.
Carbohydr Polym ; 335: 122048, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38616087

RESUMEN

Although conductive hydrogels have been widely developed currently, their low sensitivity and poor stability severely limited their practical application in flexible wearable devices. Herein, a green "stencil" anchoring strategy was proposed in this study to engineer an ultra-stable and supersensitive hydrogel by virtue of polydopamine decorating sodium alginate molecular chains as "stencil" to anchor polyaniline as conductive component. The dispersion of polyaniline was significantly improved by the sodium alginate "stencil" in the conductive hydrogel. The developed conductive hydrogel exhibited outstanding properties that outperformed most conventional ones, including extraordinary sensitivity with a gauge factor of 38.2 and excellent stability with negligible shifting upon long-term cyclic stretching. Moreover, the conductive hydrogel displayed great self-adhesion and reliable self-healing performance endowed by its abundant catechol groups, hydrogen bondings and π-π stackings, respectively. Furthermore, the prepared hydrogel was also assembled as flexible strain and self-powered sensors, which displayed excellent sensing performance, indicating great potential in human-machine interactions, information transmission and road transportation.

20.
Small ; : e2401622, 2024 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-38682610

RESUMEN

Single-network hydrogels are often too fragile to withstand mechanical loading, whereas double-network hydrogels typically exhibit significant hysteresis during cyclic stretching-releasing process due to the presence of a sacrificial network. Consequently, it is a considerable challenge for designing hydrogels that are both low in hysteresis and high in toughness for applications requiring dynamic mechanical loads. Herein, the study introduced a novel "sliding tangle island" strategy for creating tough and low-hysteresis hydrogels, which are prepared through in situ polymerization of highly concentrated acrylamides (AM) to form numerous entanglements within the MXene spacing without any chemical crosslinker. The MXene entangled with long polyacrylamide (PAM) chains to form tangle island that served as a relay station to transmit stress to neighboring molecular chains. This mechanism helps alleviate stress concentration and enhances energy dissipation efficiency, thereby reducing mechanical hysteresis. The resulting hydrogel exhibited exceptional properties, including high stretchability (≈900%), low hysteresis (less than 7%), high toughness (1.34 MJ m-3), and excellent sensing performance to rival the commercial hydrogel electrode. Therefore, this work sheds light on feasible design of energy dissipation structure to reduce the hysteresis of the composite hydrogels.

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