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1.
Int J Biol Sci ; 20(12): 4767-4780, 2024.
Article in English | MEDLINE | ID: mdl-39309426

ABSTRACT

Background: The important role of nucleobindin 2 (NUCB2) in various cancers has been recently recognized. However, its biological functions and regulatory mechanisms in hepatocellular carcinoma (HCC) remain unclear. Methods: The expression level of NUCB2 in HCC was assessed using public databases, immunohistochemistry, and Western blotting. The effects of NUCB2 on cell proliferation and metastasis were investigated using colony formation, EdU, Transwell assays, and an in vivo mouse xenograft model. Regulation of E2F4 by NUCB2 was identified by protein half-life and in vivo ubiquitylation assays. The relationship between E2F4 and prostaglandin reductase 1 (PTGR1) was investigated by qRT-PCR, RT-PCR, and chromatin immunoprecipitation assays. Results: This study found that NUCB2 expression was significantly higher in HCC tissues than in normal liver tissues, and patients with high expression displayed shorter survival rates. Inhibition of NUCB2 reduced the proliferation and metastatic potential of HCC cells in vitro and in vivo. NUCB2 depletion reduced PTGR1 expression, which reduced cell proliferation and migration. Our findings suggested that NUCB2 suppressed E2F4 degradation by interacting with E2F4. Additionally, increased E2F4 levels facilitated PTGR1 transcription by directly binding to the PTGR1 promoter. Conclusion: This study demonstrated the oncogenic properties of NUCB2 in HCC and suggested that NUCB2 facilitates hepatocellular carcinoma progression by activating the E2F4/PTGR1 axis.


Subject(s)
Carcinoma, Hepatocellular , Cell Proliferation , E2F4 Transcription Factor , Liver Neoplasms , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/genetics , Humans , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Liver Neoplasms/genetics , Cell Proliferation/genetics , Animals , Mice , E2F4 Transcription Factor/metabolism , E2F4 Transcription Factor/genetics , Cell Line, Tumor , DNA-Binding Proteins/metabolism , DNA-Binding Proteins/genetics , Mice, Nude , Gene Expression Regulation, Neoplastic , Male , Cell Movement/genetics , Female , Mice, Inbred BALB C
2.
Int J Mol Sci ; 25(17)2024 Aug 31.
Article in English | MEDLINE | ID: mdl-39273448

ABSTRACT

In view of the current problems of slow crystallization rate, varying grain sizes, complex process conditions, and low safety in the preparation of CL-20/TNT cocrystal explosives in the laboratory, an opposite spray crystallization method is provided to quickly prepare ultrafine explosive cocrystal particles. CL-20/TNT cocrystal explosive was prepared using this method, and the obtained cocrystal samples were characterized by electron microscopy morphology, differential thermal analysis, infrared spectroscopy, and X-ray diffraction analysis. The effects of spray temperature, feed ratio, and preparation method on the formation of explosive cocrystal were studied, and the process conditions of the pneumatic atomization spray crystallization method were optimized. The crystal plane binding energy and molecular interaction forces between CL-20 and TNT were obtained through molecular dynamic simulation, and the optimal binding crystal plane and cocrystal mechanism were analyzed. The theoretical calculation temperature of the binding energy was preliminarily explored in relation to the preparation process temperature of cocrystal explosives. The mechanical sensitivity of ultrafine CL-20/TNT cocrystal samples was tested. The results showed that choosing acetone as the cosolvent, a spraying temperature of 30 °C, and a feeding ratio of 1:1 was beneficial for the formation and growth of cocrystal. The prepared CL-20/TNT cocrystal has a particle size of approximately 10 µm. The grain size is small, and the crystallization rate is fast. The impact and friction sensitivity of ultrafine CL-20/TNT cocrystal samples were significantly reduced. The experimental process conditions are simple and easy to control, and the safety of the preparation process is high, providing certain technical support for the preparation of high-quality cocrystal explosives.


Subject(s)
Crystallization , Explosive Agents , Molecular Dynamics Simulation , Trinitrotoluene , Crystallization/methods , Explosive Agents/chemistry , Trinitrotoluene/chemistry , X-Ray Diffraction , Temperature
3.
Int J Hyperthermia ; 41(1): 2406889, 2024.
Article in English | MEDLINE | ID: mdl-39317933

ABSTRACT

OBJECTIVE: This study aimed to explore marker genes and their potential molecular mechanisms involved in US-guided MWA for glioma in mice. METHOD: The differentially expressed genes (DEGs1 and DEGs2) and lncRNAs (DELs1 and DELs2) were obtained between Non (glioma tissues without MWA) and T0 groups (0h after MWA), as well as between Non and T24 groups (24h after MWA). The down-regulation cluster genes (CONDOWNDEGs) and upregulation cluster genes (CONUPDEGs) were identified by time series analysis. Candidate genes were obtained by overlapping CONDOWNDEGs with downregulation DEGs (DOWNDEGs)1 and DOWNDEGs2, as well as CONUPDEGs with up-regulation DEGs (UPDEGs)1 and UPDEGs2. The expressions of immune checkpoints and inflammatory factors, gene set enrichment analysis (GSEA), and protein subcellular localization were performed. The eXpression2Kinases (X2K), GeneMANIA, transcription factor (TF), and competing endogenous (ce) RNA regulatory networks were conducted. The expression of marker genes was validated by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Five marker genes (IL32, VCAM1, IL34, NFKB1 and CXCL13) were identified, which were connected with immune-related functions. Two immune checkpoints (CD96 and TIGIT) and six inflammatory factors played key roles in US-guided MWA for glioma. ceRNA regulatory networks revealed that miR-625-5p, miR-625-3p, miR-31-5p and miR-671-5p were associated with target genes. qRT-PCR indicated both IL32, VCAM1, and NFKB1 were potential markers under US-guided MWA-related time series analysis. CONCLUSION: The use of US-guided MWA might be a practical method for influencing the function of target genes, regulating time frames to decrease inflammation, and stimulating immune responses in glioma therapy.


Subject(s)
Glioma , Glioma/genetics , Glioma/surgery , Animals , Mice , Microwaves/therapeutic use , Transcriptome , Male , Brain Neoplasms/genetics , Brain Neoplasms/surgery
4.
Anal Biochem ; 696: 115672, 2024 Sep 16.
Article in English | MEDLINE | ID: mdl-39293645

ABSTRACT

The integration of fiber optics and plasmonic sensors is promising to improve the practical usability over conventional bulky sensors and systems. To achieve high sensitivity, it typically requires fabrication of well-defined plasmonic nanostructures on optical fibers, which greatly increases the cost and complexity of the sensors. Here, we present a fiber-optic sensor system by using chemical absorption of gold nanoparticles and a replaceable configuration. By functioning gold nanoparticles with aptamers or antibodies, we demonstrate the applications in chemical sensing using two different modes. Measuring shift in resonance wavelength enables the Pb2+ detection with a high linearity and a limit of detection of 0.097 nM, and measuring absorption peak amplitude enables the detection of E. coli in urinary tract infection with a dynamic range between 103 to 108 CFU/mL. The high sensitivity, simple fabrication and disposability of this sensing approach could pave the way for point-of-care testing with fiber-optic plasmonic sensors.

5.
Chembiochem ; : e202400732, 2024 Sep 25.
Article in English | MEDLINE | ID: mdl-39322624

ABSTRACT

Guided by molecular networking based on single-molecule stretching assay, an unprecedented pyranonaphthoquinone, methyl kalafunginate (1) and five known compounds 2-6 were isolated from Streptomyces tanashiensis DSM 731. Compound 1 was characterized through a combination of spectroscopic techniques, including 1D and 2D NMR analysis, ECD calculation, and X-ray crystallography. Interestingly, we discovered that compound 1 was spontaneously converted from kalafungin (4) in methanol solution. All isolated compounds were assessed for their cytotoxic potential against a panel of five human cancer cell lines: A549, HepG2, BxPC-3, SW620, and C4-2B. Compounds 1, 2, 4, and 5 exhibited remarkable cytotoxicity with IC50 values below 2.382 µM, suggesting their potential as promising anticancer agents. These findings highlight the significance of using a combined approach of single-molecule stretching assays and molecular networking for efficiently discovering novel natural products with potential therapeutic applications.

6.
Chem Commun (Camb) ; 2024 Sep 19.
Article in English | MEDLINE | ID: mdl-39295449

ABSTRACT

A novel Sb3+-Yb3+ co-doped Cs2NaScCl6 double perovskite with multimode luminescence and efficient excitation-dependent emission is proposed. Upon Sb3+-Yb3+ co-substitution in Cs2NaScCl6, NIR emission at 995 nm is greatly enhanced. A new STE emission peaking at 570 nm appears. Its great potential in anti-counterfeiting, LEDs and night vision is successfully demonstrated.

7.
Clin Imaging ; 114: 110247, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39146827

ABSTRACT

PURPOSE: To assess the anatomical complexity of the left atrial appendage (LAA) using fractal dimension (FD) based on cardiac computed tomography angiography (CTA) and the association between LAA FD and LAA thrombosis. MATERIALS AND METHODS: Patients with atrial fibrillation (AF) who underwent both cardiac CTA and transesophageal echocardiography (TEE) between December 2018 and December 2022 were retrospectively analyzed. Patients were categorized into normal (n = 925), circulatory stasis (n = 82), and thrombus groups (n = 76) based on TEE results and propensity score matching (PSM) was performed for subsequent analysis. FD was calculated to quantify the morphological heterogeneity of LAA. Independent risk factors for thrombus were screened using logistic regression. The diagnostic performance of FD and CHA2DS2-VaSc score for predicting thrombus was evaluated using the area under the receiver operating characteristics curve (AUC). RESULTS: LAA FD was higher in the thrombus group (1.61 [1.49, 1.70], P < 0.001) than in the circulatory stasis (1.33 [1.18, 1.47]) and normal groups (1.30 [1.18, 1.42]) both before and after PSM. LAA FD was also an independent risk factor in the thrombus (OR [odds ratio] = 570,861.15 compared to normal, 41,122.87 compared to circulatory stasis; all P < 0.001) and circulatory stasis group (OR = 98.87, P = 0.001) after PSM. The diagnostic performance of LAA FD was significantly better than the CHA2DS2-VaSc score in identifying thrombus. CONCLUSIONS: Patients with high LAA FD are more likely to develop LAA thrombus, and the use of FD provides an effective method for assessing the risk of thrombosis in AF patients, thereby guiding individualized clinical treatment.


Subject(s)
Atrial Appendage , Atrial Fibrillation , Echocardiography, Transesophageal , Fractals , Thrombosis , Humans , Atrial Fibrillation/diagnostic imaging , Atrial Fibrillation/complications , Female , Male , Atrial Appendage/diagnostic imaging , Retrospective Studies , Middle Aged , Thrombosis/diagnostic imaging , Thrombosis/etiology , Aged , Echocardiography, Transesophageal/methods , Computed Tomography Angiography/methods , Risk Factors
8.
World J Gastroenterol ; 30(31): 3717-3725, 2024 Aug 21.
Article in English | MEDLINE | ID: mdl-39193003

ABSTRACT

BACKGROUND: Small cell lung carcinoma (SCLC) is highly susceptible to metastasis in the early stages of the disease. However, the stomach is an uncommon site of metastasis in SCLC, and only a few cases of this type of metastasis have been reported. Therefore, SCLC gastric metastases have not been systematically characterized and are easily missed and misdiagnosed. CASE SUMMARY: We report three cases of gastric metastasis from SCLC in this article. The first patient presented primarily with cough, hemoptysis, and epigastric fullness. The other two patients presented primarily with abdominal discomfort, epigastric distension, and pain. All patients underwent gastroscopy and imaging examinations. Meanwhile, the immunohistochemical results of the lesions in three patients were suggestive of small cell carcinoma. Finally, the three patients were diagnosed with gastric metastasis of SCLC through a comprehensive analysis. The three patients did not receive appropriate treatment and died within a short time. CONCLUSION: Here, we focused on summarizing the characteristics of gastric metastasis of SCLC to enhance clinicians' understanding of this disease.


Subject(s)
Gastroscopy , Lung Neoplasms , Small Cell Lung Carcinoma , Stomach Neoplasms , Humans , Stomach Neoplasms/pathology , Lung Neoplasms/secondary , Lung Neoplasms/pathology , Male , Small Cell Lung Carcinoma/secondary , Small Cell Lung Carcinoma/pathology , Small Cell Lung Carcinoma/diagnostic imaging , Middle Aged , Fatal Outcome , Aged , Female , Tomography, X-Ray Computed , Immunohistochemistry , Biopsy
9.
Eur J Radiol ; 179: 111650, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39116778

ABSTRACT

PURPOSE: To construct a nomogram for predicting lymphovascular invasion (LVI) in N0 stage non-small cell lung cancer (NSCLC) using dual-energy computed tomography (DECT) findings combined with clinical findings. METHODS: We retrospectively recruited 135 patients with N0 stage NSCLC from two hospitals underwent DECT before surgery and were divided into development cohort (n = 107) and validation cohort (n = 28). The clinical findings (baseline characteristics, biochemical markers, serum tumor markers and Immunohistochemical markers), DECT-derived parameters (iodine concentration [IC], effective atomic number [Eff-Z] and normalized iodine concentration [NIC], iodine enhancement [IE] and NIC ratio [NICr]) and Fractal dimension (FD) were collected and measured. A nomogram was constructed using significant findings to predict LVI in N0 stage NSCLC and was externally validated. RESULTS: Multivariable analysis revealed that lymphocyte count (LYMPH, odds ratio [OR]: 3.71, P=0.014), IC in arterial phase (ICa, OR: 1.25, P=0.021), NIC in venous phase (NICv, OR: 587.12, P=0.009) and FD (OR: 0.01, P=0.033) were independent significant factors for predicting LVI in N0 stage NSCLC, and were used to construct a nomogram. The nomogram exhibited robust predictive capabilities in both the development and validation cohort, with AUCs of 0.819 (95 % CI: 72.6-90.4) and 0.844 (95 % CI: 68.2-95.8), respectively. The calibration plots showed excellent agreement between the predicted probabilities and the actual rates of positive LVI, on external validation. CONCLUSIONS: Combination of clinical and DECT imaging findings could aid in predicting LVI in N0 stage NSCLC using significant findings of LYMPH, ICa, NICv and FD.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Lymphatic Metastasis , Neoplasm Invasiveness , Neoplasm Staging , Nomograms , Tomography, X-Ray Computed , Humans , Carcinoma, Non-Small-Cell Lung/diagnostic imaging , Carcinoma, Non-Small-Cell Lung/pathology , Male , Female , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/pathology , Middle Aged , Tomography, X-Ray Computed/methods , Retrospective Studies , Aged , Lymphatic Metastasis/diagnostic imaging , Radiography, Dual-Energy Scanned Projection/methods , Adult , Predictive Value of Tests , Reproducibility of Results
10.
Heliyon ; 10(14): e34496, 2024 Jul 30.
Article in English | MEDLINE | ID: mdl-39114074

ABSTRACT

The grey wolf optimizer is a widely used parametric optimization algorithm. It is affected by the structure and rank of grey wolves and is prone to falling into the local optimum. In this study, we propose a grey wolf optimizer for fusion cell-like P systems. Cell-like P systems can parallelize computation and communicate from cell membrane to cell membrane, which can help the grey wolf optimizer jump out of the local optimum. Design new convergence factors and use different convergence factors in other cell membranes to balance the overall exploration and utilization capabilities of the algorithm. At the same time, dynamic weights are introduced to accelerate the convergence speed of the algorithm. Experiments are performed on 24 test functions to verify their global optimization performance. Meanwhile, a support vector machine model optimized by the grey wolf optimizer for fusion cell-like P systems has been developed and tested on six benchmark datasets. Finally, the optimizing ability of grey wolf optimizer for fusion cell-like P systems on constrained optimization problems is verified on three real engineering design problems. Compared with other algorithms, grey wolf optimizer for fusion cell-like P systems obtains higher accuracy and faster convergence speed on the test function, and at the same time, it can find a better parameter set stably for the optimization of support vector machine parameters, in addition to being more competitive on constrained engineering design problems. The results show that grey wolf optimizer for fusion cell-like P systems improves the searching ability of the population, has a better ability to jump out of the local optimum, has a faster convergence speed, and has better stability.

11.
Front Oncol ; 14: 1351393, 2024.
Article in English | MEDLINE | ID: mdl-39114311

ABSTRACT

Objective: By utilizing machine learning, we can identify genes that are associated with recurrence, invasion, and tumor stemness, thus uncovering new therapeutic targets. Methods: To begin, we obtained a gene set related to recurrence and invasion from the GEO database, a comprehensive gene expression database. We then employed the Weighted Gene Co-expression Network Analysis (WGCNA) to identify core gene modules and perform functional enrichment analysis on them. Next, we utilized the random forest and random survival forest algorithms to calculate the genes within the key modules, resulting in the identification of three crucial genes. Subsequently, one of these key genes was selected for prognosis analysis and potential drug screening using the Kaplan-Meier tool. Finally, in order to examine the role of CDC20 in lung adenocarcinoma (LUAD), we conducted a variety of in vitro and in vivo experiments, including wound healing assay, colony formation assays, Transwell migration assays, flow cytometric cell cycle analysis, western blotting, and a mouse tumor model experiment. Results: First, we collected a total of 279 samples from two datasets, GSE166722 and GSE31210, to identify 91 differentially expressed genes associated with recurrence, invasion, and stemness in lung adenocarcinoma. Functional enrichment analysis revealed that these key gene clusters were primarily involved in microtubule binding, spindle, chromosomal region, organelle fission, and nuclear division. Next, using machine learning, we identified and validated three hub genes (CDC45, CDC20, TPX2), with CDC20 showing the highest correlation with tumor stemness and limited previous research. Furthermore, we found a close association between CDC20 and clinical pathological features, poor overall survival (OS), progression-free interval (PFI), progression-free survival (PFS), and adverse prognosis in lung adenocarcinoma patients. Lastly, our functional research demonstrated that knocking down CDC20 could inhibit cancer cell migration, invasion, proliferation, cell cycle progression, and tumor growth possibly through the MAPK signaling pathway. Conclusion: CDC20 has emerged as a novel biomarker for monitoring treatment response, recurrence, and disease progression in patients with lung adenocarcinoma. Due to its significance, further research studying CDC20 as a potential therapeutic target is warranted. Investigating the role of CDC20 could lead to valuable insights for developing new treatments and improving patient outcomes.

12.
Nano Lett ; 24(33): 10348-10354, 2024 Aug 21.
Article in English | MEDLINE | ID: mdl-39109804

ABSTRACT

Carrier transport capacity with high mobility and long-range diffusion length holds particular significance for the advancement of modern optoelectronic devices. Herein, we have unveiled the carrier dynamics and transport properties of a pristine violet phosphorus (VP) nanosheet by a transient absorption microscopy. Under the excitation (2.41 eV) above the exciton band, two photoinduced absorption peaks with the energy difference of approximately 520 meV emerge within a broadband transient absorption background which originates from the prompt generation of free carriers and the concomitant formation of excitons (lifetime of 467.21 ps). This observation is consistent with the established band-edge model of VP. Intriguingly, we have determined the ambipolar diffusion coefficient and mobility of VP to be approximately 47.32 cm2·s-1 and 1798 cm2·V-1·s-1, respectively, which further indicate a long-range carrier transport of approximately 2.10 µm. This work unveils the significant carrier transport capacity of VP, highlighting its potential for future optoelectronic and excitonic applications.

13.
Molecules ; 29(16)2024 Aug 08.
Article in English | MEDLINE | ID: mdl-39202836

ABSTRACT

3,4-bis(3-nitrofurazan-4-yl) furoxan (DNTF) is an explosive with excellent performance, and the use of DNTF as a high-energy component is of great significance for improving the comprehensive performance of weapons. To explore the effect of DNTF on low-melting-point molten carrier explosives, the compatibility between DNTF and other low-melting-point explosives was analyzed by differential scanning calorimetry, and mechanical sensitivity was tested. The compatibility and cohesive energy density between DNTF and other low-melting-point explosives were calculated by Materials Studio. The results showed that DNTF has good compatibility with most low-melting-point explosives, and the peak temperature change of the mixed system formed by melt-casting is not obvious. Among them, DNTF has the best compatibility with MTNP, TNT, and DNAN; moderate compatibility with DFTNAN and DNP; and the worst compatibility with DNMT. The sensitivity test results indicate that the combination of DNTF and TNT has the most significant reduction in mechanical sensitivity. DFTNAN and MTNP have better stability than DNTF and can generate strong interaction forces with DNTF. Other low-melting-point explosives mixed with DNTF have lower intermolecular forces than DNTF. The DNTF/MTNP system requires the most energy to phase change when heated compared to other mixed systems and is the least sensitive to heat. The DNTF/DNMT system has the lowest cohesive energy density and is the most sensitive to heat.

14.
Front Pharmacol ; 15: 1456796, 2024.
Article in English | MEDLINE | ID: mdl-39188952

ABSTRACT

Osteoporosis is a common systemic metabolic disease characterized by a decrease in bone density and bone mass, destruction of bone tissue microstructure, and increased bone fragility leading to fracture susceptibility. Pharmacological treatment of osteoporosis is the focus of current research, and anti-osteoporosis drugs usually play a role in inhibiting bone resorption, promoting bone formation, and having a dual role. However, most of the drugs have the disadvantages of single target and high toxic and side effects. There are many types of traditional Chinese medicines (TCM), from a wide range of sources and mostly plants. Herbal plants have unique advantages in regulating the relationship between osteoporosis and the immune system, acupuncture therapy has significant therapeutic effects in combination with medicine for osteoporosis. The target cells and specific molecular mechanisms of TCM in preventing and treating osteoporosis have not been fully elucidated. At present, there is a lack of comprehensive understanding of the pathological mechanism of the disease. Therefore, a better understanding of the pathological signaling pathways and key molecules involved in the pathogenesis of osteoporosis is crucial for the design of therapeutic targets and drug development. In this paper, we review the development and current status of anti-osteoporosis drugs currently in clinical application and under development to provide relevant basis and reference for drug prevention and treatment of osteoporosis, with the aim of promoting pharmacological research and new drug development.

15.
Transl Oncol ; 49: 102095, 2024 Nov.
Article in English | MEDLINE | ID: mdl-39167955

ABSTRACT

BACKGROUND: The immune status is closely linked to cancer progression, metastasis, and prognosis. Lipid metabolism, crucial for reshaping immune status, plays a key role in regulating the advancement of lung adenocarcinoma (LUAD) and deserves further investigation. METHODS: This study classifies LUAD patients into different immune subtypes based on lipid metabolism-related genes and compares the clinical characteristics among these subtypes. Single-multi COX analysis screens out key genes related to prognosis, and a risk feature and prognostic model are constructed. Cell cloning, scratch, transwell, western blotting and flow cytometry cell cycle analysis to detect the function of key genes. A subcutaneous tumor animal model is used to investigate the in vivo function and molecular mechanisms of key genes. RESULTS: LUAD patients are classified into three immune subtypes, among which C3 subtype has lower immune status and higher frequency of gene mutations, and show lower immunoreactivity in immunotherapy. COX analysis identified a prognostic model for four lipid metabolism factors (IGFBP1, NR0B2, PPARA, and POMC). IGFBP1, a core gene in this model, is highly expressed in the C3 subtype. Functionally, knocking down IGFBP1 significantly inhibits tumor cell cloning, scratch, and migration abilities, and downregulates the expression of cell cycle and EMT-related proteins. Knocking down IGFBP1 significantly inhibits tumor burden (P < 0.05). Mechanistically, knocking down IGFBP1 inhibits the activation of PPARα to regulate tumor cell growth. CONCLUSIONS: This study found that lipid metabolism genes are closely related to LUAD, and IGFBP1 may be a key gene in regulating tumor growth and development.

16.
Int J Mol Med ; 54(4)2024 10.
Article in English | MEDLINE | ID: mdl-39129313

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a fatal pulmonary disease that requires further investigation to understand its pathogenesis. The present study demonstrated that secreted phosphoprotein 1 (SPP1) was aberrantly highly expressed in the lung tissue of patients with IPF and was significantly positively associated with macrophage and T­cell activity. Cell localization studies revealed that SPP1 was primarily overexpressed in macrophages, rather than in T cells. Functionally, knocking down SPP1 expression in vitro inhibited the secretion of fibrosis­related factors and M2 polarization in macrophages. Furthermore, knocking down SPP1 expression inhibited the macrophage­induced epithelial­to­mesenchymal transition in both epithelial and fibroblastic cells. Treatment with SPP1 inhibitors in vivo enhanced lung function and ameliorated pulmonary fibrosis. Mechanistically, SPP1 appears to promote macrophage M2 polarization by regulating the JAK/STAT3 signaling pathway both in vitro and in vivo. In summary, the present study found that SPP1 promotes M2 polarization of macrophages through the JAK2/STAT3 signaling pathway, thereby accelerating the progression of IPF. Inhibition of SPP1 expression in vivo can effectively alleviate the development of IPF, indicating that SPP1 in macrophages may be a potential therapeutic target for IPF.


Subject(s)
Idiopathic Pulmonary Fibrosis , Janus Kinase 2 , Macrophages , Osteopontin , STAT3 Transcription Factor , Signal Transduction , STAT3 Transcription Factor/metabolism , Janus Kinase 2/metabolism , Idiopathic Pulmonary Fibrosis/pathology , Idiopathic Pulmonary Fibrosis/metabolism , Macrophages/metabolism , Humans , Animals , Male , Mice , Osteopontin/metabolism , Osteopontin/genetics , Disease Progression , Epithelial-Mesenchymal Transition/genetics , Female , Mice, Inbred C57BL , Middle Aged
17.
J Transl Med ; 22(1): 720, 2024 Aug 05.
Article in English | MEDLINE | ID: mdl-39103842

ABSTRACT

BACKGROUND: Fatigue is one of the most common neurological symptoms reported post coronavirus disease 2019 (COVID-19) infection. In order to establish effective early intervention strategies, more emphasis should be placed on the correlation between fatigue and cortical neurophysiological changes, especially in healthcare workers, who are at a heightened risk of COVID-19 infection. METHODS: A prospective cohort study was conducted involving 29 COVID-19 medical workers and 24 healthy controls. The assessment included fatigue, sleep and health quality, psychological status, and physical capacity. Functional near-infrared spectroscopy (fNIRS) was employed to detect activation of brain regions. Bilateral primary motor cortex (M1) excitabilities were measured using single- and paired-pulse transcranial magnetic stimulation. Outcomes were assessed at 1, 3, and 6 months into the disease course. RESULTS: At 1-month post-COVID-19 infection, 37.9% of patients experienced severe fatigue symptoms, dropping to 10.3% at 3 months. Interestingly, the remarkable decreased activation/excitability of bilateral prefrontal lobe (PFC) and M1 were closely linked to fatigue symptoms after COVID-19. Notably, greater increase in M1 region excitability correlated with more significant fatigue improvement. Re-infected patients exhibited lower levels of brain activation and excitability compared to single-infection patients. CONCLUSIONS: Both single infection and reinfection of COVID-19 lead to decreased activation and excitability of the PFC and M1. The degree of excitability improvement in the M1 region correlates with a greater recovery in fatigue. Based on these findings, targeted interventions to enhance and regulate the excitability of M1 may represent a novel strategy for COVID-19 early rehabilitation. TRIAL REGISTRATION: The Ethics Review Committee of Xijing Hospital, No. KY20232051-F-1; www.chictr.org.cn , ChiCTR2300068444.


Subject(s)
COVID-19 , Fatigue , Health Personnel , Motor Cortex , Prefrontal Cortex , Transcranial Magnetic Stimulation , Humans , COVID-19/physiopathology , Fatigue/physiopathology , Male , Female , Longitudinal Studies , Adult , Prefrontal Cortex/physiopathology , Prefrontal Cortex/diagnostic imaging , Motor Cortex/physiopathology , Middle Aged , SARS-CoV-2/isolation & purification , Prospective Studies , Spectroscopy, Near-Infrared , Cohort Studies
18.
Acad Radiol ; 2024 Aug 16.
Article in English | MEDLINE | ID: mdl-39153960

ABSTRACT

PURPOSE: To develop a model based on conventional CT signs and the tumor microenvironment immune types (TIMT) to predict the durable clinical benefits (DCB) of postoperative adjuvant chemotherapy in non-small cell lung cancer (NSCLC). METHODS AND MATERIALS: A total of 205 patients with NSCLC underwent preoperative CT and were divided into two groups: DCB (progression-free survival (PFS) ≥ 18 months) and non-DCB (NDCB, PFS <18 months). The density percentiles of PD-L1 and CD8 + tumor-infiltrating lymphocytes (TIL) were quantified to estimate the TIMT. Clinical characteristics and conventional CT signs were collected. Multivariate logistic regression was employed to select the most discriminating parameters, construct a predictive model, and visualize the model as a nomogram. Receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were used to evaluate prediction performance and clinical utility. RESULTS: Precisely 118 patients with DCB and 87 with NDCB in NSCLC received postoperative adjuvant chemotherapy. TIMT was statistically different between the DCB and NDCB groups (P < 0.05). Clinical characteristics (neuron-specific enolase, squamous cell carcinoma antigen, Ki-76, and cM stage) and conventional CT signs (spiculation, bubble-like lucency, pleural retraction, maximum diameter, and CT value of the venous phase) varied between the four TIMT groups (P < 0.05). Furthermore, clinical characteristics (lymphocyte count [LYMPH] and cM stage) and conventional CT signs (bubble-like lucency and Pleural effusion) differed between the DCB and NDCB groups (P < 0.05). Multivariate analysis revealed that TIMT, cM stage, LYMPH, and pleural effusion were independently associated with DCB and were used to construct a nomogram. The area under the curve (AUC) of the combined model was 0.70 (95%CI: 0.64-0.76), with sensitivity and specificity of 0.73 and 0.60, respectively. CONCLUSION: Conventional CT signs and the TIMT offer a promising approach to predicting clinical outcomes for patients treated with postoperative adjuvant chemotherapy in NSCLC.

19.
Mol Divers ; 2024 Aug 29.
Article in English | MEDLINE | ID: mdl-39207663

ABSTRACT

Idiopathic Pulmonary Fibrosis (IPF) is a disease characterized by pulmonary interstitial fibrosis and collagen proliferation, currently lacking effective therapeutic options. The combined use of Celastrol and Ligustrazine has been proved to synergistically improve the pathological processes of inflammation and fibrosis. In earlier studies, we designed and synthesized a Celastrol-Ligustrazine compound CL-001, though its role in IPF remains unclear. Here, the effects and mechanisms of CL-001 in bleomycin (BLM)-induced IPF were investigated. In vivo, CL-001 significantly improved lung function, reduced pulmonary inflammation, and decreased collagen deposition, thereby preventing the progression of IPF. In vitro, CL-001 concurrently inhibited both Smad-dependent and Smad-independent pathways, thereby suppressing TGF-ß1-induced epithelial-mesenchymal transition (EMT) and epithelial cell migration. This inhibitory effect was superior to that of Celastrol or Ligustrazine administered alone. Additionally, CL-001 significantly increased the level of apoptosis and promoted the expression of apoptosis-related proteins (Caspase-8 and PARP), ultimately leading to widespread apoptosis in activated lung epithelial cells. In summary, CL-001 exhibits excellent anti-IPF effects both in vitro and in vivo, suggesting its potential as a novel candidate drug for IPF, warranting further development.

20.
Langmuir ; 40(35): 18670-18682, 2024 Sep 03.
Article in English | MEDLINE | ID: mdl-39163637

ABSTRACT

Water oxidation is an endothermic and kinetics-sluggish reaction; the research of photoanodes with photothermal and cocatalytic properties is of great significance. Herein, BiVO4/CoAl2O4 film photoanodes were studied for solar water splitting through coupling spinel p-type CoAl2O4 nanoparticles on n-type BiVO4 films. Compared to the BiVO4 photoanode, better performance was observed on the BiVO4/CoAl2O4 photoanode during water oxidation. A photocurrent of 3.47 mA/cm2 was produced on the BiVO4/CoAl2O4 photoanode at 1.23 V vs RHE, which is two-fold to the BiVO4 photoanode (1.70 mA/cm2). Additionally, the BiVO4/CoAl2O4 photoanodes showed an acceptable stability for water oxidation. The BiVO4/CoAl2O4 photoanode being of higher water oxidation performance could be attributed to the presence of p-n heterojunction, cocatalytic, and photothermal effects. In specific, under the excitation of λ < 520 nm light, the holes produced in/on BiVO4 can be transferred to CoAl2O4 owing to the p-n heterojunctions of BiVO4/CoAl2O4. Meanwhile, the temperature on the BiVO4/CoAl2O4 photoanode rises quickly up to ∼53 °C under AM 1.5 G irradiation due to the photothermal property of CoAl2O4 through capturing the 520 < λ < 720 nm light. The temperature rising on the BiVO4/CoAl2O4 photoanode improves the cocatalytic activity of CoAl2O4 and modifies the wettability of BiVO4/CoAl2O4 for effective water oxidation.

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