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1.
Talanta ; 278: 126497, 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38955104

RESUMO

Unveiling the intricate relationship between cancer and Golgi viscosity remains an arduous endeavor, primarily due to the lack of Golgi-specific fluorescent probes tailored for viscosity measurement. Considering this formidable obstacle, we have triumphed over the challenge by devising a bespoke Golgi-specific viscosity probe, aptly named GOL-V. This ingenious innovation comprises the viscosity rotor BODIPY intricately tethered to the Golgi-targeting moiety benzsulfamide. GOL-V exhibits remarkable sensitivity to fluctuations in viscosity, the fluorescence intensity of GOL-V increased 114-fold when the viscosity value was increased from 2.63 to 937.28 cP. Owing to its remarkable capacity to suppress the TICT state under conditions of heightened viscosity. Moreover, its efficacy in sensitively monitoring Golgi viscosity alterations within living cells is also very significant. Astonishingly, our endeavors have culminated in not only the visualization of Golgi viscosity at the cellular and tissue levels but also in the clinical tissue samples procured from cancer patients. Harnessing the prowess of GOL-V, we have successfully demonstrated that Golgi viscosity could serve as a discerning marker for detecting the presence of cancer. The convergence of these exceptional attributes firmly establishes GOL-V as an immensely potent instrument, holding immense potential in the realm of cancer diagnosis.

2.
Mol Ther Oncol ; 32(2): 200816, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38948919

RESUMO

The presence of a poly(A) tail is indispensable for the post-transcriptional regulation of gene expression in cancer. This dynamic and modifiable feature of transcripts is under the control of various nuclear and cytoplasmic proteins. This study aimed to develop a novel cytoplasmic poly(A)-related signature for predicting prognosis, clinical attributes, tumor immune microenvironment (TIME), and treatment response in hepatocellular carcinoma (HCC). Utilizing RNA sequencing (RNA-seq) data from The Cancer Genome Atlas (TCGA), non-negative matrix factorization (NMF), and principal-component analysis (PCA) were employed to categorize HCC patients into three clusters, thus demonstrating the pivotal prognostic role of cytoplasmic poly(A) tail regulators. Furthermore, machine learning algorithms such as least absolute shrinkage and selection operator (LASSO), survival analysis, and Cox proportional hazards modeling were able to distinguish distinct cytoplasmic poly(A) subtypes. As a result, a 5-gene signature derived from TCGA was developed and validated using International Cancer Genome Consortium (ICGC) HCC datasets. This novel classification based on cytoplasmic poly(A) regulators has the potential to improve prognostic predictions and provide guidance for chemotherapy, immunotherapy, and transarterial chemoembolization (TACE) in HCC.

3.
J Clin Oncol ; : JCO2302261, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38950321

RESUMO

PURPOSE: To assess whether the integration of PD-1 inhibitor with total neoadjuvant therapy (iTNT) can lead to an improvement in complete responses (CRs) and favors a watch-and-wait (WW) strategy in patients with proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). PATIENTS AND METHODS: We conducted a prospective, multicenter, randomized, open-label, phase II trial using a pick-the-winner design. Eligible patients with clinical T3-4 and/or N+ rectal adenocarcinoma were randomly assigned to group A for short-course radiotherapy (SCRT) followed by six cycles of consolidation immunochemotherapy with capecitabine and oxaliplatin and toripalimab or to group B for two cycles of induction immunochemotherapy followed by SCRT and the rest four doses. Either total mesorectal excision or WW was applied on the basis of tumor response. The primary end point was CR which included pathological CR (pCR) after surgery and clinical CR (cCR) if WW was applicable, with hypothesis of an increased CR of 40% after iTNT compared with historical data of 25% after conventional TNT. RESULTS: Of the 130 patients enrolled, 121 pMMR/MSS patients were evaluable (62 in group A and 59 in group B). At a median follow-up of 19 months, CR was achieved at 56.5% in group A and 54.2% in group B. Both groups fulfilled the predefined statistical hypothesis (P < .001). Both groups reported a pCR rate of 50%. Respectively, 15 patients in each group underwent WW and remained disease free. The most frequent grade 3 to 4 toxicities were thrombocytopenia and neutropenia. Patients in group A had higher rate of cCR (43.5% v 35.6%) at restaging and lower rate of grade 3 to 4 thrombocytopenia (24.2% v 33.9%) during neoadjuvant treatment. CONCLUSION: The iTNT regimens remarkably improved CR rates in pMMR/MSS LARC compared with historical benchmark with acceptable toxicity. Up-front SCRT followed by immunochemotherapy was selected for future definitive study.

4.
Front Chem ; 12: 1427451, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38952891

RESUMO

In solid propellants, combustion catalysts play a crucial role. Here, we introduce a convenient method for the self-assembly of UIO-66 (Mn) in the presence of water, leading to the preparation of Mn/C aerogels. The aerogels were successfully utilized in the thermocatalytic decomposition of ammonium perchlorate (AP). The results indicate that the incorporation of 2% mass fraction of Mn/C aerogels enhances the peak temperature of AP decomposition by approximately 87.5°C. Mn/C aerogels demonstrate excellent catalytic performance. In combination with kinetics, we propose a thermal catalytic mechanism.

5.
World J Gastroenterol ; 30(23): 2959-2963, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38946873

RESUMO

In this editorial, we comment on the article entitled "Stage at diagnosis of colorectal cancer through diagnostic route: Who should be screened?" by Agatsuma et al. Colorectal cancer (CRC) is emerging as an important health issue as its incidence continues to rise globally, adversely affecting the quality of life. Although the public has become more aware of CRC prevention, most patients lack screening awareness. Some poor lifestyle practices can lead to CRC and symptoms can appear in the early stages of CRC. However, due to the lack of awareness of the disease, most of the CRC patients are diagnosed already at an advanced stage and have a poor prognosis.


Assuntos
Neoplasias Colorretais , Detecção Precoce de Câncer , Humanos , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/prevenção & controle , Neoplasias Colorretais/epidemiologia , Detecção Precoce de Câncer/métodos , Qualidade de Vida , Estadiamento de Neoplasias , Programas de Rastreamento/métodos , Programas de Rastreamento/normas , Prognóstico , Colonoscopia , Incidência , Conhecimentos, Atitudes e Prática em Saúde , Estilo de Vida
6.
iScience ; 27(6): 110117, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38947521

RESUMO

Dysregulated host immune responses contribute to disease severity and worsened prognosis in COVID-19 infection and the underlying mechanisms are not fully understood. In this study, we observed that IL-33, a damage-associated molecular pattern molecule, is significantly increased in COVID-19 patients and in SARS-CoV-2-infected mice. Using IL-33-/- mice, we demonstrated that IL-33 deficiency resulted in significant decreases in bodyweight loss, tissue viral burdens, and lung pathology. These improved outcomes in IL-33-/- mice also correlated with a reduction in innate immune cell infiltrates, i.e., neutrophils, macrophages, natural killer cells, and activated T cells in inflamed lungs. Lung RNA-seq results revealed that IL-33 signaling enhances activation of inflammatory pathways, including interferon signaling, pathogen phagocytosis, macrophage activation, and cytokine/chemokine signals. Overall, these findings demonstrate that the alarmin IL-33 plays a pathogenic role in SARS-CoV-2 infection and provides new insights that will inform the development of effective therapeutic strategies for COVID-19.

7.
Int J Chron Obstruct Pulmon Dis ; 19: 1491-1513, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38957709

RESUMO

Background: Chronic obstructive pulmonary disease (COPD) stands as a predominant cause of global morbidity and mortality. This study aims to elucidate the relationship between pyroptosis-related genes (PRGs) and COPD diagnosis in the context of immune infiltration, ultimately proposing a PRG-based diagnostic model for predicting COPD outcomes. Methods: Clinical data and PRGs of COPD patients were sourced from the GEO database. The "ConsensusClusterPlus" package was employed to generate molecular subtypes derived from PRGs that were identified through differential expression analysis and LASSO Cox analysis. A diagnostic signature including eight genes (CASP4, CASP5, ELANE, GPX4, NLRP1, GSDME, NOD1and IL18) was also constructed. Immune cell infiltration calculated by the ESTIMATE score, Stroma scores and Immune scores were also compared on the basis of pyroptosis-related molecular subtypes and the risk signature. We finally used qRT - PCR to detect the expression levels of eight genes in COPD patient and normal. Results: The diagnostic model, anchored on eight PRGs, underwent validation with an independent experimental cohort. The area under the receiver operating characteristic (ROC) curves (AUC) for the diagnostic model showcased values of 0.809, 0.765, and 0.956 for the GSE76925, GSE8545, and GSE5058 datasets, respectively. Distinct expression patterns and clinical attributes of PRGs were observed between the comparative groups, with functional analysis underscoring a disparity in immune-related functions between them. Conclusion: In this study, we developed a potential as diagnostic biomarkers for COPD and have a significant role in modulating the immune response. Such insights pave the way for novel diagnostic and therapeutic strategies for COPD.


Assuntos
Bases de Dados Genéticas , Valor Preditivo dos Testes , Doença Pulmonar Obstrutiva Crônica , Piroptose , Humanos , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/imunologia , Piroptose/genética , Perfilação da Expressão Gênica , Pulmão/imunologia , Masculino , Feminino , Pessoa de Meia-Idade , Marcadores Genéticos , Estudos de Casos e Controles , Transcriptoma , Idoso , Reprodutibilidade dos Testes , Predisposição Genética para Doença , Prognóstico
8.
Meat Sci ; 216: 109585, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38959640

RESUMO

In this study, the effect of sodium alginate and quaternized chitosan bis-polysaccharide-based shell transport curcumin nano-emulsions (Cur@QCS/SA) on the microbiological, physicochemical properties, quality characteristics of Harbin red sausage during storage is investigated. According to the microbiological results, the shelf life of Harbin red sausage is extended from 3 d to 6 d by adding 0.15% Cur@QCS/SA, and Bacillus is the most predominant bacterial before 6 d. Additionally, the physicochemical properties change significantly, the pH, weight loss (WL), water holding capacity (WHC), water activity (aw), L*, and a* of red sausage decrease gradually with the extension of storage time, as well as b*, lipid oxidation, proteolysis increase significantly (P < 0.05). Secondly, it is found that 0.15% treatment group can better maintain the quality characteristics of Harbin red sausage according to texture profile analysis (TPA), electronic nose (E-nose), and electronic tongue (E-tongue) (P < 0.05). This study provides a new way for nano-emulsions in food applications and a new option for the preservation of Harbin red sausage as well as other low-temperature meat products.

9.
Sci Rep ; 14(1): 15114, 2024 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956155

RESUMO

Wheat straw returning is a common agronomic measure in the farmland. Understanding organic carbon transformation is of great significance for carbon budget under the premise of widespread distribution of cadmium (Cd) contaminated soils. An incubation experiment was conducted to assess the influence of Cd contamination on the decomposition and accumulation of total organic carbon (TOC) as well as the composition and abundance of bacterial communities in eight soil types with wheat straw addition. The results showed that inhibition of Cd contamination on microbially mediated organic carbon decomposition was affected by soil types. The lower cumulative C mineralization and higher TOC content could be observed in the acidic soils relative to that in the alkaline soils. The content of Cd in soil exhibits different effects on the inhibition in decomposition of TOC. The high dosage level of Cd had stronger inhibitory impact due to its high toxicity. The decomposition of TOC was restricted by a reduction in soil bacterial abundance and weakening of bacterial activities. Redundancy analysis (RDA) indicated that Proteobacteria and Gemmatimonadetes were abundant in alkaline Cd-contaminated soils with wheat straw addition, while Bacteroidetes dominated cumulative C mineralization in acidic Cd-contamination soils. Moreover, the abundance of predicted functional bacteria indicated that high-dose Cd-contamination and acid environment all inhibited the decomposition of TOC. The present study suggested that pH played an important role on carbon dynamics in the Cd-contaminated soils with wheat straw addition.


Assuntos
Cádmio , Carbono , Microbiologia do Solo , Poluentes do Solo , Solo , Triticum , Cádmio/metabolismo , Cádmio/análise , Triticum/metabolismo , Triticum/química , Poluentes do Solo/análise , Poluentes do Solo/metabolismo , Carbono/metabolismo , Carbono/análise , Solo/química , Bactérias/metabolismo , Biodegradação Ambiental , Concentração de Íons de Hidrogênio
10.
Sci Rep ; 14(1): 15108, 2024 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956257

RESUMO

Diabetic retinopathy is one of the most common microangiopathy in diabetes, essentially caused by abnormal blood glucose metabolism resulting from insufficient insulin secretion or reduced insulin activity. Epidemiological survey results show that about one third of diabetes patients have signs of diabetic retinopathy, and another third may suffer from serious retinopathy that threatens vision. However, the pathogenesis of diabetic retinopathy is still unclear, and there is no systematic method to detect the onset of the disease and effectively predict its occurrence. In this study, we used medical detection data from diabetic retinopathy patients to determine key biomarkers that induce disease onset through back propagation neural network algorithm and hierarchical clustering analysis, ultimately obtaining early warning signals of the disease. The key markers that induce diabetic retinopathy have been detected, which can also be used to explore the induction mechanism of disease occurrence and deliver strong warning signal before disease occurrence. We found that multiple clinical indicators that form key markers, such as glycated hemoglobin, serum uric acid, alanine aminotransferase are closely related to the occurrence of the disease. They respectively induced disease from the aspects of the individual lipid metabolism, cell oxidation reduction, bone metabolism and bone resorption and cell function of blood coagulation. The key markers that induce diabetic retinopathy complications do not act independently, but form a complete module to coordinate and work together before the onset of the disease, and transmit a strong warning signal. The key markers detected by this algorithm are more sensitive and effective in the early warning of disease. Hence, a new method related to key markers is proposed for the study of diabetic microvascular lesions. In clinical prediction and diagnosis, doctors can use key markers to give early warning of individual diseases and make early intervention.


Assuntos
Algoritmos , Biomarcadores , Retinopatia Diabética , Redes Neurais de Computação , Humanos , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/sangue , Biomarcadores/sangue , Análise por Conglomerados , Masculino , Feminino , Diagnóstico Precoce , Pessoa de Meia-Idade , Hemoglobinas Glicadas/análise , Hemoglobinas Glicadas/metabolismo
11.
Front Endocrinol (Lausanne) ; 15: 1379398, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38957444

RESUMO

Background: Diabetic gastroparesis is a common complication in patient with diabetes. Dietary intervention has been widely used in the treatment of diabetic gastroparesis. The aim of this study is to evaluate the role of diet in the treatment of diabetic gastroparesis. Methods: This systematic review was conducted a comprehensive search of randomized controlled trials using dietary interventions for the treatment of diabetic gastroparesis up to 9 November 2023. The primary outcomes were gastric emptying time and clinical effect, while fasting blood glucose, 2-hour postprandial blood glucose and glycosylated hemoglobin were secondary outcomes. Data analysis was performed using RevMan 5.4 software, and publication bias test was performed using Stata 15.1 software. Results: A total of 15 randomized controlled trials involving 1106 participants were included in this review. The results showed that patients with diabetic gastroparesis benefit from dietary interventions (whether personalized dietary care alone or personalized dietary care+routine dietary care). Compared with routine dietary care, personalized dietary care and personalized dietary care+routine dietary care can shorten the gastric emptying time, improve clinical efficacy, and reduce the level of fasting blood glucose, 2-hour postprandial blood glucose and glycosylated hemoglobin. Conclusions: Limited evidence suggests that dietary intervention can promote gastric emptying and stabilize blood glucose control in patients with diabetic gastroparesis. Dietary intervention has unique potential in the treatment of diabetic gastroparesis, and more high-quality randomized controlled trials are needed to further validate our research results. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023481621.


Assuntos
Gastroparesia , Humanos , Gastroparesia/dietoterapia , Gastroparesia/terapia , Gastroparesia/etiologia , Esvaziamento Gástrico , Glicemia/metabolismo , Complicações do Diabetes/dietoterapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Diabetes Mellitus/dietoterapia
12.
Front Microbiol ; 15: 1427806, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38962116

RESUMO

Altitude and ultraviolet (UV) radiation may affect the community composition and distribution of microorganisms in soil ecosystems. In this study, 49 soil samples from 10 locations were collected from different elevations on the eastern Pamir Plateau and analyzed for soil microbial community structure and function using high-throughput sequencing. The results showed that soil samples from different elevations of the eastern Pamir Plateau contained 6834 OTUs in 26 phyla and 399 genera. The dominant phyla common to different elevations were Actinobacteria, Proteobacteria, Bacteroidota, Acidobacteriota, and Gemmatimonadota. The dominant genera were Rubrobacter, Sphingomonas, Nocardioides, and Solirubrobacter. Species richness increased slightly with elevation, and there were significant differences in community composition between the elevations. Elevation and UV exposure are important factors that drive changes in bacterial communities. The results of the KEGG pathway showed that drug resistance, antineoplastic, aging, replication, and repair were enhanced and then slightly decreased with increasing elevation. Bacterial communities at different elevations were rich in radiation-resistant microorganisms, and the main genera were Rubrobacter, Sphingomonas, Nocardioides, Pontibacter, and Streptomyces. The findings have shown the composition and distribution of bacterial communities at different elevations on the Eastern Pamir Plateau. Potentially radiation tolerant microbial species were also examined. The results are of considerable importance for the succession of bacterial microorganisms in the plateau region, the study of radiation tolerant bacterial germplasm resources, and the application of biofunctionality.

14.
J Trace Elem Med Biol ; 85: 127492, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38964025

RESUMO

Low levels of the indispensable trace element selenium (Se) can cause oxidative stress and disrupt environmental homeostasis in humans and animals. Selenoprotein S (Selenos), of which Se is a key component, is a member of the selenoprotein family involved in various biological processes. This study aimed to investigate whether low-level SELENOS gene expression can induce oxidative stress and decrease the antioxidative capacity of chondrocytes. Compared with control cells, SELENOS-knockdown ATDC5 cells showed substantially higher dihydroethidium, reactive oxygen species and malondialdehyde levels, and lower superoxide dismutase (SOD) expression. Knockout of the gene in C57BL/6 mice increased the 8-hydroxy-2-deoxyguanosine level considerably and decreased SOD expression in cartilages relative to the levels in wild-type mice. The results showed that the increased nuclear factor erythroid 2-related factor 2/heme oxygenase-1 signaling mediated by low-level SELENOS expression was involved in oxidative damage. The proliferative zone of the cartilage growth plate of SELENOS-knockout mice was shortened, suggesting cartilage differentiation dysfunction. In conclusion, this study confirmed that low-level Selenos expression plays a role in oxidative stress in cartilages.

15.
Med ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38964333

RESUMO

BACKGROUND: Immune checkpoint inhibitors (ICIs) provide modest but unsatisfactory benefits for extensive-stage small cell lung cancer (ES-SCLC). Developing strategies for treating ES-SCLC is critical. METHODS: We preliminarily explored the outcomes of salvage low-dose radiotherapy (LDRT) plus ICI on refractory SCLC patients. Next, we evaluated the combinational efficacy in murine SCLC. The tumor immune microenvironment (TIME) was analyzed for mechanistic study. Subsequently, we conducted a multicenter, prospective phase II trial that administered concurrent thoracic LDRT plus chemoimmunotherapy to treatment-naive ES-SCLC patients (MATCH trial, NCT04622228). The primary endpoint was confirmed objective response rate (ORR), and the key secondary endpoints included progression-free survival (PFS) and safety. FINDINGS: Fifteen refractory SCLC patients treated with LDRT plus ICI were retrospectively reviewed. The ORR was 73.3% (95% confidence interval [CI], 44.9-92.2). We identified a specific dose of LDRT (15 Gy/5 fractions) that exhibited growth retardation and improved survival in murine SCLC when combined with ICIs. This combination recruited a special T cell population, TCF1+ PD-1+ CD8+ stem-like T cells, from tumor-draining lymph nodes into the TIME. The MATCH trial showed a confirmed ORR of 87.5% (95% CI, 75.9-94.8). The median PFS was 6.9 months (95% CI, 5.4-9.3). CONCLUSIONS: These findings verified that LDRT plus chemoimmunotherapy was safe, feasible, and effective for ES-SCLC, warranting further investigation. FUNDING: This research was funded by West China Hospital (no. ZYJC21003), the National Natural Science Foundation of China (no. 82073336), and the MATCH trial was fully funded by Roche (China) Holding Ltd. (RCHL) and Shanghai Roche Pharmaceuticals Ltd. (SRPL).

16.
Medicine (Baltimore) ; 103(27): e38798, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38968454

RESUMO

RATIONALE: Descending necrotizing mediastinitis (DNM) is a rare but serious complication of oral and cervical infections that is associated with high mortality because diagnosis can be difficult or delayed. Early diagnosis and accurate identification of the causative pathogen can significantly reduce mortality, and are critical for the management of these patients. PATIENT CONCERNS: A 56-year-old female was admitted with a sore throat and fever. The initial diagnosis was acute tonsillitis, but she was transferred to the intensive care unit after developing dyspnea. DIAGNOSES: Pleural effusion and mediastinal lesions were detected by computed tomography, and a diagnosis of DNM was confirmed by laboratory tests. INTERVENTIONS: Initial treatment consisting of ceftriaxone and vancomycin with chest tube drainage were not effective. Thoracic surgery was performed to completely remove the "moss" tissue, blood clots, and pus. Next-generation sequencing was then performed, and the anti-infective treatment was changed to imipenem and linezolid based on these results. OUTCOMES: Eventually, the patient's symptoms were controlled, all vital signs were stable, and she was successfully transferred out of the intensive care unit. LESSONS: Next-generation sequencing is a rapid and accurate method for identification of pathogens that can provide a basis for early treatment of DNM, thereby improving patient prognosis and reducing mortality.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Mediastinite , Tonsilite , Humanos , Feminino , Mediastinite/diagnóstico , Mediastinite/microbiologia , Pessoa de Meia-Idade , Tonsilite/complicações , Tonsilite/microbiologia , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Antibacterianos/uso terapêutico , Necrose , Tomografia Computadorizada por Raios X , Doença Aguda
17.
Medicine (Baltimore) ; 103(27): e38699, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38968529

RESUMO

Investigations into the therapeutic potential of Astragalus Mongholicus (AM, huáng qí) and Largehead Atractylodes (LA, bái zhú) reveal significant efficacy in mitigating the onset and progression of knee osteoarthritis (KOA), albeit with an elusive mechanistic understanding. This study delineates the primary bioactive constituents and their molecular targets within the AM-LA synergy by harnessing the comprehensive Traditional Chinese Medicine (TCM) network databases, including TCMSP, TCMID, and ETCM. Furthermore, an analysis of 3 gene expression datasets, sourced from the gene expression omnibus database, facilitated the identification of differential genes associated with KOA. Integrating these findings with data from 5 predominant databases yielded a refined list of KOA-associated targets, which were subsequently aligned with the gene signatures corresponding to AM and LA treatment. Through this alignment, specific molecular targets pertinent to the AM-LA therapeutic axis were elucidated. The construction of a protein-protein interaction network, leveraging the shared genetic markers between KOA pathology and AM-LA intervention, enabled the identification of pivotal molecular targets via the topological analysis facilitated by CytoNCA plugins. Subsequent GO and KEGG enrichment analyses fostered the development of a holistic herbal-ingredient-target network and a core target-signal pathway network. Molecular docking techniques were employed to validate the interaction between 5 central molecular targets and their corresponding active compounds within the AM-LA complex. Our findings suggest that the AM-LA combination modulates key biological processes, including cellular activity, reactive oxygen species modification, metabolic regulation, and the activation of systemic immunity. By either augmenting or attenuating crucial signaling pathways, such as MAPK, calcium, and PI3K/AKT pathways, the AM-LA dyad orchestrates a comprehensive regulatory effect on immune-inflammatory responses, cellular proliferation, differentiation, apoptosis, and antioxidant defenses, offering a novel therapeutic avenue for KOA management. This study, underpinned by gene expression omnibus gene chip analyses and network pharmacology, advances our understanding of the molecular underpinnings governing the inhibitory effects of AM and LA on KOA progression, laying the groundwork for future explorations into the active components and mechanistic pathways of TCM in KOA treatment.


Assuntos
Atractylodes , Medicamentos de Ervas Chinesas , Simulação de Acoplamento Molecular , Farmacologia em Rede , Osteoartrite do Joelho , Atractylodes/química , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/farmacologia , Osteoartrite do Joelho/tratamento farmacológico , Osteoartrite do Joelho/genética , Farmacologia em Rede/métodos , Humanos , Mapas de Interação de Proteínas , Astrágalo/química , Medicina Tradicional Chinesa/métodos , Análise de Sequência com Séries de Oligonucleotídeos , Astragalus propinquus
19.
Small ; : e2403300, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38966902

RESUMO

Pore size sieving, Donnan exclusion, and their combined effects seriously affect ion separation of membrane processes. However, traditional polymer-based membranes face some challenges in precisely controlling both charge distribution and pore size on the membrane surface, which hinders the ion separation performance, such as heavy metal ion removal. Herein, the heterocharged covalent organic framework (COF) membrane is reported by assembling two kinds of ionic COF nanosheets with opposite charges and different pore sizes. By manipulating the stacking quantity and sequence of two kinds of nanosheets, the impact of membrane surface charge and pore size on the separation performance of monovalent and multivalent ions is investigated. For the separation of anions, the effect of pore size sieving is dominant, while for the separation of cations, the effect of Donnan exclusion is dominant. The heterocharged TpEBr/TpPa-SO3H membrane with a positively charged upper layer and a negatively charged bottom layer exhibits excellent rejection of multivalent anions and cations (Ni2+, Cd2+, Cr2+, CrO4 2-, SeO3 2-, etc). The strategy provides not only high-performance COF membranes for ion separation but also an inspiration for the engineering of heterocharged membranes.

20.
Ultrasonography ; 43(4): 263-271, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38960742

RESUMO

PURPOSE: This study aimed to evaluate changes in ultrafast pulse wave velocity (ufPWV) in individuals with arterial stiffness and subclinical atherosclerosis (subAS), and to provide cutoff values. METHODS: This retrospective study recruited 231 participants, including 67 patients with subAS. The pulse wave velocity was measured at the beginning and end of systole (PWV-BS and PWVES, respectively) using ultrafast ultrasonography to assess arterial stiffness. The right and left common carotid arteries were measured separately, and laboratory metabolic parameters were also collected. Participants were balanced between groups using propensity score matching (PSM) at a 1:1 ratio, adjusting for age, sex, and waist-to-hip ratio as potential confounders. Cutoff values of ufPWV for monitoring subAS were determined via receiver operating characteristic (ROC) curve analysis. RESULTS: PWV-ES, unlike PWV-BS, was higher in the subAS subgroup than in the subAS-free group after PSM (all P<0.05). For each 1 m/s increase in left, right, and bilateral mean PWV-ES, the risk of subAS increased by 23% (95% confidence interval [CI], 1.04 to 1.46), 26% (95% CI, 1.07 to 1.52), and 38% (95% CI, 1.12 to 1.72), respectively. According to ROC analyses, predictive potential was found for left PWV-ES (cutoff value=7.910 m/s, P=0.002), right PWV-ES (cutoff value=6.615 m/s, P=0.003), and bilateral mean PWV-ES (cutoff value=7.415 m/s, P<0.001), but not for PWV-BS (all P>0.05). CONCLUSION: PWV-ES measured using ultrafast ultrasonography was significantly higher in individuals with subAS than in those without. Specific PWV-ES cutoff values showed potential for predicting an increased risk of subAS.

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