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1.
J Gastrointest Oncol ; 15(2): 730-746, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38756638

ABSTRACT

Background: Solute carrier family 16 member 1 (SLC16A1) serves as a biomarker in numerous types of cancer. Tumor immune infiltration has drawn increasing attention in cancer progression and treatment. The objective of our study was to explore the association between SLC16A1 and the tumor immune microenvironment in pancreatic ductal adenocarcinoma (PDAC). Methods: Data were obtained from The Cancer Genome Atlas. The xCell web tool was used to calculate the proportion of immune cells according to SLC16A1 expression. To further explore the mechanism of SLC16A1, immunity-related genes were screened from differentially expressed genes through weighted gene coexpression network analysis, examined via Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses, and filtrated using univariate Cox regression and least absolute shrinkage and selection operator regression model combined correlation analysis (P<0.05). Next, CIBERSORT was used to analyze the correlation between immune cells and five important genes. SLC16A1 expression and its clinical role in pancreatic cancer was clarified via immunohistochemical staining experiments. Finally, the effects of SLC16A1 on the results of cancer immunity were evaluated by in vitro experiments. Results: SLC16A1 was overexpressed in PDAC tissues and could be an independent prognostic factor. SLC16A1 was significantly negatively correlated with overall survival and suppressed the tumor immunity of PDAC. In clinic, SLC16A1 expression was significantly positively correlated with tumor progression and poor prognosis. We also found that SLC16A1 could suppress the antitumor ability of CD8+ T cells. Conclusions: SLC16A1 is a biomarker for the prognosis of PDAC and can influence the immune environment of PDAC. These findings provide new insights into the treatment of PDAC.

2.
Int J Pharm ; 656: 124115, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38614430

ABSTRACT

Fibroblast growth factor 21 (FGF21) shows great therapeutic potential in metabolic, neurodegenerative and inflammatory diseases. However, current FGF21 administration predominantly relies on injection rather than oral ingestion due to its limited stability and activity post-gastrointestinal transit, thereby hindering its clinical utility. Milk-derived exosomes (mEx) have emerged as a promising vehicle for oral drug delivery due to their ability to maintain structural integrity in the gastrointestinal milieu. To address the challenge associated with oral delivery of FGF21, we encapsulated FGF21 within mEx (mEx@FGF21) to protect its activity post-oral administration. Additionally, we modified the surface of mEx@FGF21 by introducing transferrin (TF) to enhance intestinal absorption and transport, designated TF-mEx@FGF21. In vitro results demonstrated that the surface modification of TF promoted FGF21 internalization by intestinal epithelial cells. Orally administered TF-mEx@FGF21 showed promising therapeutic effects in septic mice. This study represents a practicable strategy for advancing the clinical application of oral FGF21 delivery.


Subject(s)
Fibroblast Growth Factors , Inflammation , Sepsis , Fibroblast Growth Factors/administration & dosage , Animals , Administration, Oral , Mice , Sepsis/drug therapy , Inflammation/drug therapy , Male , Exosomes , Transferrin/administration & dosage , Transferrin/chemistry , Mice, Inbred C57BL , Milk , Humans , Drug Delivery Systems , Intestinal Absorption/drug effects
3.
Adv Healthc Mater ; 13(13): e2304304, 2024 05.
Article in English | MEDLINE | ID: mdl-38306647

ABSTRACT

Acute lung injury (ALI) is a serious inflammatory disease that causes impairment of pulmonary function. Phenotypic modulation of macrophage in the lung using fibroblast growth factor 21 (FGF21) may be a potential strategy to alleviate lung inflammation. Consequently, achieving specific delivery of FGF21 to the inflamed lung and subsequent efficient FGF21 internalization by macrophages within the lung becomes critical for effective ALI treatment. Here, an apoptotic cell membrane-coated zirconium-based metal-organic framework UiO-66 is reported for precise pulmonary delivery of FGF21 (ACM@U-FGF21) whose design is inspired by the process of efferocytosis. ACM@U-FGF21 with apoptotic signals is recognized and internalized by phagocytes in the blood and macrophages in the lung, and then the intracellular ACM@U-FGF21 can inhibit the excessive secretion of pro-inflammatory cytokines by these cells to relieve the inflammation. Utilizing the homologous targeting properties inherited from the source cells and the spontaneous recruitment of immune cells to inflammatory sites, ACM@U-FGF21 can accumulate preferentially in the lung after injection. The results prove that ACM@U-FGF21 effectively reduces inflammatory damage to the lung by modulating lung macrophage polarization and suppressing the excessive secretion of pro-inflammatory cytokines by activated immune cells. This study demonstrates the usefulness of efferocytosis-inspired ACM@U-FGF21 in the treatment of ALI.


Subject(s)
Acute Lung Injury , Fibroblast Growth Factors , Acute Lung Injury/drug therapy , Acute Lung Injury/metabolism , Animals , Mice , Fibroblast Growth Factors/metabolism , Biomimetic Materials/chemistry , Biomimetic Materials/pharmacology , Phagocytosis/drug effects , Macrophages/metabolism , Macrophages/drug effects , Apoptosis/drug effects , Metal-Organic Frameworks/chemistry , Metal-Organic Frameworks/pharmacology , Mice, Inbred C57BL , Male , Zirconium/chemistry , Cytokines/metabolism , Lung/pathology , Lung/metabolism , RAW 264.7 Cells , Humans , Nanoparticles/chemistry
4.
Mater Horiz ; 11(9): 2191-2205, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38410914

ABSTRACT

Liquid-free ionic conductive elastomers (ICEs) are ideal materials for constructing flexible electronic devices by avoiding the limitations of liquid components. However, developing all-solid-state ionic conductors with high mechanical strength, high ionic conductivity, excellent healing, and recyclability remains a great challenge. Herein, a series of liquid-free polyurethane-based ICEs with a double dynamic crosslinked structure are reported. As a result of interactions between multiple dynamic bonds (multi-level hydrogen bonds, disulfide bonds, and dynamic D-A bonds) and lithium-oxygen bonds, the optimal ICE exhibited a high mechanical strength (1.18 MPa), excellent ionic conductivity (0.14 mS cm-1), desirable healing capacity (healing efficiency >95%), and recyclability. A multi-functional wearable sensor based on the novel ICE enabled real-time and rapid detection of various human activities and enabled recognizing writing signals and encrypted information transmission. A triboelectric nanogenerator based on the novel ICE exhibited an excellent open-circuit voltage of 464 V, a short-circuit current of 16 µA, a transferred charge of 50 nC, and a power density of 720 mW m-2, enabling powering of small-scale electronic products. This study provides a feasible strategy for designing flexible sensor products and healing, self-powered devices, with promising prospects for application in soft ionic electronics.

5.
Gastrointest Endosc ; 99(1): 108-115.e1, 2024 01.
Article in English | MEDLINE | ID: mdl-37739237

ABSTRACT

BACKGROUND AND AIMS: Ultrathin EGD (UT-EGD) is an ideal tool for unsedated upper GI examination and pediatric gastroenterology but is rarely competent for EUS miniprobe (EUS-MP). We developed a UT-EGD US method (UT-EUS) and verified its clinical application value through animal experiments. METHODS: Five Bama miniature pigs were selected. Using an acoustic medium, we performed US on the duodenum, stomach, and esophagus, respectively, with conventional 20-MHz EUS miniprobe (EUS-MP-20), 20-MHz UT-EUS (UT-EUS-20), and 30-MHz UT-EUS (UT-EUS-30). The times to acquire 5 consecutive stable US images, number of identifiable wall layers, and quality and penetration depth of the images were recorded. RESULTS: No significant differences were found in the time required to obtain images between EUS-MP-20 and UT-EUS-20 at each site (P > .05). UT-EUS-30 showed more wall levels than UT-EUS-20 (P < .05). No significant differences were noted between EUS-MP-20 and UT-EUS-20 in imaging quality and penetration depth (P > .05). CONCLUSIONS: The UT-EUS is easy to use with a satisfactory image quality and has potential clinical application value.


Subject(s)
Endoscopy, Digestive System , Ultrasonics , Humans , Child , Swine , Animals , Endoscopy, Digestive System/methods , Endoscopes , Endosonography/methods , Esophagus/diagnostic imaging
7.
iScience ; 26(8): 107416, 2023 Aug 18.
Article in English | MEDLINE | ID: mdl-37564699

ABSTRACT

Simultaneous photocatalytic biorefinery and CO2 reduction to co-produce fuels and high value-added chemicals have recently attracted significant attention; however, comprehensive studies are still lacking. Herein, we report the preparation of highly crystalline oxygen-doped carbon nitride nanotubes (O-CNNTs-x) using an ammonium fluoride-assisted hydrothermal/calcination strategy. The hollow structure, high crystallinity, and O incorporation endowed the O-CNNTs-x with photocatalytic activity by considerably improving optical absorption and modulating the charge carrier motion. The lactic acid yield and CO evolution rate over O-CNNTs-2.0 reached 82.08% and 67.95 µmol g-1 h-1, which are 1.57- and 7.37-fold times higher than those of CN, respectively. Moreover, ·OH plays a key role in the oxidation half-reaction. This study offers a facile approach for fabricating highly crystalline element-doped CN with a customizable morphology and electronic properties and demonstrates the viability of co-photocatalytic CO2 reduction and biomass selective oxidation.

8.
Cell Rep ; 42(6): 112650, 2023 06 27.
Article in English | MEDLINE | ID: mdl-37314930

ABSTRACT

METTL14 (methyltransferase-like 14) is an RNA-binding protein that partners with METTL3 to mediate N6-methyladenosine (m6A) methylation. Recent studies identified a function for METTL3 in heterochromatin in mouse embryonic stem cells (mESCs), but the molecular function of METTL14 on chromatin in mESCs remains unclear. Here, we show that METTL14 specifically binds and regulates bivalent domains, which are marked by trimethylation of histone H3 lysine 27 (H3K27me3) and lysine 4 (H3K4me3). Knockout of Mettl14 results in decreased H3K27me3 but increased H3K4me3 levels, leading to increased transcription. We find that bivalent domain regulation by METTL14 is independent of METTL3 or m6A modification. METTL14 enhances H3K27me3 and reduces H3K4me3 by interacting with and probably recruiting the H3K27 methyltransferase polycomb repressive complex 2 (PRC2) and H3K4 demethylase KDM5B to chromatin. Our findings identify an METTL3-independent role of METTL14 in maintaining the integrity of bivalent domains in mESCs, thus indicating a mechanism of bivalent domain regulation in mammals.


Subject(s)
Chromatin , Histones , Methyltransferases , Animals , Mice , Chromatin/metabolism , Histones/metabolism , Lysine/metabolism , Mammals/metabolism , Mice, Knockout , Mouse Embryonic Stem Cells/metabolism , Polycomb Repressive Complex 2/metabolism , Methyltransferases/metabolism
9.
J Control Release ; 358: 368-381, 2023 06.
Article in English | MEDLINE | ID: mdl-37121517

ABSTRACT

The management of acute kidney injury (AKI) imposes a significant medical burden. Due to the lack of effective drug transport vehicles, the administration of therapeutic agents for AKI cannot obtain the desired therapeutic effects. Kidney-targeted nanoparticles for renal delivery of drugs have shown promising potential as an emerging strategy for AKI therapy. However, these exogenous nanoparticles are rapidly cleared in the body and fail to achieve the expected renal targeting efficiency. Herein, we prepared the kidney targeting peptide-modified renal tubular epithelial cell membrane to coat zeolite imidazolate framework-8 nanoparticles for FGF21 delivery (KMZ@FGF21) for AKI treatment. KMZ@FGF21 could be efficiently internalized by renal cells and exhibited antioxidative, antiapoptotic and anti-inflammatory effects. A septic AKI murine model was established to assess the in vivo performance of KMZ@FGF21. The results showed that injected KMZ@FGF21 specifically accumulated in the injured kidney and exerted good renoprotective effects. This study provides an innovative thread for precise drug delivery in the treatment of various renal diseases.


Subject(s)
Acute Kidney Injury , Biomimetics , Mice , Animals , Kidney/metabolism , Acute Kidney Injury/drug therapy , Acute Kidney Injury/metabolism , Antioxidants , Kidney Tubules
10.
Front Public Health ; 10: 1049822, 2022.
Article in English | MEDLINE | ID: mdl-36582381

ABSTRACT

Objective: The study aimed to investigate the influencing factors of psychological symptoms in relation to job burnout and occupational stress among coal miners in Xinjiang, so as to provide data support for enterprises in an effort to help them identify internal psychological risk factors and improve the mental health of coal miners. Methods: A cross-sectional study was carried out. A total of 12 coal mines were selected using the stratified cluster random sampling method and 4,109 coal miners were investigated by means of online electronic questionnaires. The Symptoms Check List-90 (SCL-90), Chinese Maslach Burnout Inventory (CMBI), and Job Demand-Control (JDC) model were respectively used to measure the status of psychological symptoms, job burnout, and occupational stress among coal miners. The mediation analysis was performed through structural equation modeling (SEM) by using Analysis of Moment Structure (AMOS). Results: The prevalence of psychological symptoms was higher in the occupational stress group than in the non-occupational stress group, and increased with job burnout (P < 0.05). The multivariate logistic regression analysis results showed that mild (OR = 1.401, 95% CL: 1.165, 1.685), moderate (OR = 2.190, 95% CL: 1.795, 2.672), or severe levels of burnout (OR = 6.102, 95% CL: 3.481, 10.694) and occupational stress (OR = 1.462, 95% CL: 1.272, 1.679) were risk factors for psychological symptoms in coal miners. The results of structural equation modeling indicated that occupational stress (ß = 0.11, P = 0.002) and job burnout (ß = 0.46, P = 0.002) had significant positive direct effects on psychological symptoms, and job burnout was an intermediate variable between occupational stress and psychological symptoms. Conclusion: High levels of job burnout and occupational stress were risk factors for psychological symptoms. Both occupational stress and job burnout had direct effects on psychological symptoms, and occupational stress could also have an indirect effect on coal miners' psychological symptoms through the intermediate variable of job burnout.


Subject(s)
Burnout, Professional , Occupational Stress , Humans , Cross-Sectional Studies , Occupational Stress/epidemiology , Burnout, Professional/epidemiology , Burnout, Professional/psychology , China/epidemiology , Coal
11.
Article in English | MEDLINE | ID: mdl-36231557

ABSTRACT

Participation in gateball sports may improve the well-being of older individuals in the context of active aging. However, the mechanisms of the effect need a social viewpoint. A random sample of 337 valid data points was gathered from seven cities in the Chinese province of Hunan. Structural equation modeling, fuzzy set qualitative comparative analysis, and other techniques examined the standard structure and causal links between involvement in gateball sports, social capital, and elderly people's well-being. According to structural equation modeling, playing gateball sports may improve elderly people's well-being, and social capital may influence this link to some extent. The engagement in gateball sports and social capital work in concert to promote well-being, according to a qualitative comparative study of the fuzzy sets that identified four patterns of "A, B, C, and D" antecedent constructs that do so in elderly people.


Subject(s)
Social Capital , Sports , Aged , Aging , China , Cities , Humans
12.
Article in English | MEDLINE | ID: mdl-36011820

ABSTRACT

The prospects of China's sports sector hinge on how sports cities can thrive sustainably in the context of the new global pandemic, unlocking consumer potential and boosting domestic demand. In this study, 35 Chinese cities were chosen as research samples, and research methods such as literature, logical analysis, and fuzzy-set qualitative comparative analysis were used to select conditional variables such as government policy promotion and assistance, expert human resources, sports competitions and events, stadiums and facilities, and sponsorship by sports enterprises to examine how Chinese sports-consuming cities can develop sustainably. The research discovered that sports contests and events, as well as stadiums and facilities, are the essential prerequisites for the sustainable growth of sports-consuming cities, and that diverse combinations of the two may play a vital role in different circumstances. For the sustainable development of sports-consuming cities, there are four clusters and three models, which correspond to the "Venue + Event" model (Clusters 1 and 2), the "Event-led" model (Cluster 3), and the "Venue-led" model (Cluster 4). To encourage the high-quality growth of China's sports business, each city may establish its development strategy based on its unique qualities. The goal is to supply Chinese expertise for the long-term growth of Western sports cities.


Subject(s)
Sports , Sustainable Development , China , Cities , Government , Humans
13.
Int J Pharm ; 624: 121971, 2022 Aug 25.
Article in English | MEDLINE | ID: mdl-35787461

ABSTRACT

Acute lung injury (ALI) is one of the most common comorbidities associated with sepsis and can lead to acute respiratory distress syndrome. Intense inflammatory response due to excessive activation and uncontrolled infiltration of neutrophils are the central processes in the development of sepsis-induced ALI. In this study, a biomimetic nanoplatform that is a neutrophil membrane-coated liposome-loaded acidic fibroblast growth factor (aFGF@NMLs), which can selectively target the inflamed lung and effectively alleviate sepsis-induced ALI via inflammation suppression, was constructed. In vitro findings revealed that aFGF@NMLs has pro-inflammatory cytokine binding capabilities and can promote cellular uptake, substantially attenuate inflammatory responses, and enhance cellular antioxidant capacity. The in vivo results show that aFGF@NMLs can specifically accumulate in injured lungs in ALI mice after intravenous injection, thereby reducing the secretion of pro-inflammatory cytokines, inhibiting pulmonary cell apoptosis, and promoting lung function recovery. In conclusion, aFGF@NMLs demonstrated anti-inflammatory effects, mitigated the progression of ALI, and contributed to the disease prognosis. This research offers an innovative strategy and concept for the clinical treatment of diseases related to pulmonary inflammation.


Subject(s)
Acute Lung Injury , Sepsis , Acute Lung Injury/drug therapy , Animals , Lipopolysaccharides/pharmacology , Liposomes/pharmacology , Lung/metabolism , Mice , Mice, Inbred C57BL , Neutrophils/metabolism
14.
Front Pharmacol ; 13: 881320, 2022.
Article in English | MEDLINE | ID: mdl-35656291

ABSTRACT

Cardiac injury is recognized as a major contributor to septic shock and a major component of the multiple organ dysfunction associated with sepsis. Emerging evidence shows that regulation of the intramyocardial oxidative stress and inflammatory response has a promising prospect. Basic fibroblast growth factor (bFGF) exhibits anti-inflammatory and antioxidant properties. In this study, red blood cell membrane-camouflaged poly (lactide-co-glycolide) nanoparticles were synthesized to deliver bFGF (bFGF-RBC/NP) for sepsis-induced cardiac injury. The in vitro experiments revealed that bFGF-RBC/NP could protect cardiomyocytes from oxidative and inflammatory damage. In addition, the antioxidant and anti-inflammatory properties of bFGF-RBC/NP against cardiac injury were validated using data from in vivo experiments. Collectively, our study used bFGF for the treatment of sepsis-induced cardiac injury and confirmed that bFGF-RBC/NP has therapeutic benefits in the treatment of myocardial dysfunction. This study provides a novel strategy for preventing and treating cardiac injury in sepsis.

15.
Bioengineered ; 13(5): 11694-11705, 2022 05.
Article in English | MEDLINE | ID: mdl-35510503

ABSTRACT

Diabetic retinopathy (DR) has become the leading cause of blindness among adults at working age. Previous studies have implicated circ_0001897 in the development of DR. In this study, we investigated the functional roles and mechanisms of circ_0001897 in high glucose-induced angiogenesis and inflammation. Peripheral blood samples from DR patients and healthy controls were collected to examine circ_0001897 expression, which demonstrated a significant upregulation of circ_0001897 in DR patients. To investigate the functional role and mechanisms of circ_0001897, human retinal microvascular endothelial cells (HRECs) were treated with high glucose (HG) to establish an in vitro DR model of endothelial cells. HG treatment induced the upregulation of circ_0001897 in HRECs, and enhanced cell proliferation, inflammatory responses, as well as in vitro angiogenesis. Circ_0001897 knockdown significantly attenuated the cell proliferation, inflammatory responses, and angiogenesis induced by HG treatment. Mechanistically, circ_0001897 sponged and inhibited the activity of mir-29c-3p, which in turn regulates the downstream target transforming growth factor beta 2 (TGFB2). The effects of circ_0001897 knockdown could be rescued by mir-29c-3p inhibitor or TGFB2 overexpression. Collectively, our data demonstrated the novel role of circ_0001897/mir-29c-3p/TGFB2 axis in regulating HG-induced inflammation and angiogenesis of HRECs. These findings suggest that targeting circ_0001897 could serve as an intervention strategy to ameliorate DR.


Subject(s)
Diabetic Retinopathy , MicroRNAs , Adult , Cell Proliferation/genetics , Diabetic Retinopathy/genetics , Diabetic Retinopathy/metabolism , Endothelial Cells/metabolism , Glucose/metabolism , Glucose/toxicity , Humans , Inflammation/genetics , Inflammation/metabolism , MicroRNAs/metabolism , Neovascularization, Pathologic/genetics
16.
Small ; 18(20): e2107697, 2022 May.
Article in English | MEDLINE | ID: mdl-35218307

ABSTRACT

The exploitation of clean energy promotes the exploration of next-generation lithium-ion batteries (LIBs) with high energy-density, long life, high safety, and low cost. Ni-rich layered cathode materials are one of the most promising candidates for next-generation LIBs. Numerous studies focusing on the synthesis and modifications of the layered cathode materials are published every year. Many physical features of precursors, such as density, morphology, size distribution, and microstructure of primary particles pass to the resulting cathode materials, thus significantly affecting their electrochemical properties and battery performance. This review focuses on the recent advances in the controlled synthesis of hydroxide precursors and the growth of particles. The essential parameters in controlled coprecipitation are discussed in detail. Some innovative technologies for precursor modifications and for the synthesis of novel precursors are highlighted. In addition, future perspectives of the development of hydroxide precursors are presented.

17.
Article in English | MEDLINE | ID: mdl-35020594

ABSTRACT

High-frequency endoscopic ultrasound (HFEUS) imaging is an important tool commonly used in clinical practice for imaging hollow organs. The virtual source synthetic aperture (VSSA) method is effective in improving the imaging quality of HFEUS. However, interference from the motor control unit severely affects the accuracy of the conventional delay and sum (DAS) method, thus compromising the effectiveness of VSSA. In this article, a new computational method based on phase correction was proposed to overcome these shortcomings, which is named phase-corrected-and-sum (PCAS). Meanwhile, the parameters of coherence factor weighting (CFW) can be obtained from the correlation coefficient of the superimposed signals to further increase the imaging quality. Three kinds of imaging experiments were designed to evaluate the proposed method. Compared with the conventional method, the results show that the PCAS-CFW method improves the lateral resolution by about 10% and the contrast-to-noise ratio (CNR) by about 44%. Therefore, this proposed method is capable of significantly improving HFEUS image quality, and this method can be easily integrated into current HFEUS imaging systems, showing great potential for clinical applications.


Subject(s)
Endosonography , Image Processing, Computer-Assisted , Algorithms , Image Processing, Computer-Assisted/methods , Phantoms, Imaging , Signal-To-Noise Ratio , Ultrasonography/methods
18.
Ultrasonics ; 121: 106669, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35007837

ABSTRACT

Insufficient imaging penetration and large data acquisition are two of the major challenges of high-frequency ultrasound imaging. Based on the good autocorrelation properties of chirp signal and the feasibility of using compressed sensing theory to reconstruct high-quality ultrasound images with low sampling requirements, this paper proposed a chirp coded excitation combined with compressed sensing (CCE-CS) technique for high-frequency endoscopic ultrasound (HFEUS) imaging. The feasibility of the method was verified by a brief theoretical analysis, and the relevant parameters were selected and analyzed according to the actual engineering situation. Simulated phantoms and in-vitro tissue experiments were used to evaluate the performance of the CCE-CS. Simulation results demonstrate that CCE-CS is capable of reducing the impact of reconstruction errors and improving imaging quality through comparison with conventional methods. The reduction of reconstruction data had less impact on penetration depth, resolution and general contrast general contrast-to-noise ratio (gCNR), and the reconstructed image was closer to the original image with a maximum improvement of 37% in peak signal-to-noise ratio (PSNR). Moreover, comparisons were conducted on the digestive tract of swine, and the results show that CCE-CS is also feasible in the in-vitro environment. These results demonstrated that CCE-CS method has good potential for application to improve the imaging quality of HFEUS while reducing the sampling rate.


Subject(s)
Endosonography/methods , Intestines/diagnostic imaging , Animals , Computer Simulation , Image Processing, Computer-Assisted , In Vitro Techniques , Signal-To-Noise Ratio , Swine
19.
J Ethnopharmacol ; 285: 114858, 2022 Mar 01.
Article in English | MEDLINE | ID: mdl-34826543

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease with unknown etiology. Oxytropis falcata Bunge (O. falcata) is a 1-35 cm high perennial clustered herb, also known as edaxia, has viscosity and a special smell, and is mainly distributed in the western areas of China. The root of O. falcata has a diameter of 6 mm, is straight and deep, dark red and its stems are shortened, woody and multibranched. O. falcata has heat-clearing, detoxification, analgesic, anti-inflammatory, antibacterial, hemostatic and antitumor activities. Furthermore, O. falcata has excellent anti-inflammatory and analgesic effects, and it is one of the three major anti-inflammatory drugs in Tibetan medicine, known as "the king of herbs". Total flavonoids of Oxytropis falcata Bunge (FOFB) were previously extracted, and their pharmacological activities are consistent with those of the whole herb. In this study, FOFB was extracted from O. falcata by ethanol extraction, and the mechanism of FOFB on IPF was verified by in vivo and in vitro experiments. AIM OF THE STUDY: In this study, we aimed to observe the effects of FOFB on idiopathic pulmonary fibrosis. MATERIALS AND METHODS: In in vivo experiments, an IPF rat model was established by bleomycin induction. The rats were treated with FOFB (100, 200, 400 mg kg-1·d-1) for 4 weeks. Masson staining and the expression of TGF-ß, p-Smad2, p-Smad3 and Smad7 in the lung tissue of rats were detected. In in vitro experiments, we perfused normal rats with FOFB (100, 200, 400 mg kg-1·d-1) and obtained the corresponding drug-containing serum. The HFL-1 cell model induced by TGF-ß1 was used to detect the corresponding indices through intervention with drug-containing serum. The best intervention time for drug-containing serum was detected by the CCK-8 method. Changes in apoptosis, cytoskeleton and rough endoplasmic reticulum structure were detected. Finally, the expression of TGF-ß, p-Smad2, p-Smad3 and Smad7 in cells was examined. RESULTS: In vivo, Masson staining indicated that the degree of pulmonary fibrosis increased significantly, the expression of TGF-ß, p-smad2 and p-Smad3 increased significantly, and the expression of Smad7 decreased in the model group. We found that the degree of pulmonary fibrosis gradually decreased and that the inhibition of the TGF-ß/Smad signaling pathway became more obvious with increasing FOFB dose. FOFB (400 mg kg-1·d-1) significantly improved the degree of pulmonary fibrosis in rats. In in vitro experiments, the CCK-8 results showed that 120 h was the best intervention time for drug-containing serum. In the model group, there was no obvious apoptosis or changes in microfilaments and microtubules, the number of rough endoplasmic reticulum increased, and the expression of TGF-ß, p-Smad2 and p-Smad3 increased significantly, while the expression of Smad7 decreased significantly. We found that with the increase in drug-containing serum concentration, the apoptosis, cytoskeleton and degree of destruction of the rough endoplasmic reticulum in the HFL-1 cell model also increased, and the inhibition of the TGF-ß/Smad signaling pathway became more pronounced; the effect of the drug-containing serum administered with FOFB (400 mg kg-1·d-1) was the most significant. CONCLUSIONS: The results suggest that FOFB can improve the occurrence and development of IPF. The effect of FOFB on IPF may be mediated by inhibition of the TGF-ß1/Smad signaling pathway.


Subject(s)
Flavonoids/therapeutic use , Oxytropis/chemistry , Phytotherapy , Pulmonary Fibrosis/drug therapy , Smad Proteins/metabolism , Transforming Growth Factor beta1/metabolism , Animals , Antibiotics, Antineoplastic/toxicity , Bleomycin/toxicity , Cell Line , Female , Gene Expression Regulation/drug effects , Humans , Male , Plant Extracts/chemistry , Random Allocation , Rats , Rats, Sprague-Dawley , Signal Transduction , Smad Proteins/genetics , Specific Pathogen-Free Organisms , Transforming Growth Factor beta1/genetics
20.
Article in English | MEDLINE | ID: mdl-36619196

ABSTRACT

Objective: This study was aimed to explore the mechanism of Sishen Wan (SSW) in treating ulcerative colitis (UC) in a rat model of spleen-kidney yang deficiency pattern by regulating gut microbiota and the content of butyric acid in short-chain fatty acid (SCFAs) and restoring regulatory T (Treg)/T helper type 17 (Th17) balance from the perspective of the correlation between gut microbiota and immune function. Methods: The UC rat model of spleen-kidney yang deficiency pattern was established by the method of combining disease and syndrome (intragastric administration of senna leaf, subcutaneous injection of hydrocortisone, and enema with 2,4-dinitrobenzenesulfonic acid (DNBS)/ethanol solution). After successful modeling, rats were randomly divided into six groups: the blank group, model group, low-, middle-, and high-dose Sishen Wan groups, and mesalazine group. Samples were taken after continuous administration for 3 weeks. The general conditions and body weight of the rats were observed and recorded, and the disease activity index (DAI) score was calculated. Colonic mucosal injury was observed, and a colonic mucosal damage index (CMDI) score was calculated. Histopathological changes in colon tissues were determined by hematoxylin and eosin (H&E) staining, and the histopathological score (HS) was calculated. The serum levels of transforming growth factor-ß1 (TGF-ß1), interleukin (IL)-6, IL-10, and IL-17 were determined by enzyme-linked immunosorbent assay (ELISA) assays. The expression of TGF-ß1, signal transducer and activator of transcription 3 (STAT3), and peroxisome proliferator-activated receptor γ (PPARγ) was determined by Western blot analysis. The proportion of Th17 and Treg cells in colon tissue was determined by flow cytometry. The relative abundance of gut microbiota was determined by 16S rDNA sequencing, and the concentration of butyric acid of SCFAs was determined by gas chromatography-mass spectrometry (GC-MS). Results: Administration of SSW significantly improved the pathological changes of colon tissue in UC rats and could attenuate the DAI and CMDI scores, and the HS. SSW significantly decreased the serum levels of IL-6 and IL-17 and increased the serum levels of TGF-ß1 and IL-10. In addition, SSW increased the expression of TGF-ß1 and PPARγ and decreased the expression of STAT3 in colon tissue in a dose-dependent manner. Furthermore, SSW significantly decreased the proportion of Th17 cells and increased the proportion of Treg cells in colon tissue. Additionally, SSW altered the gut microbiota, including an increase in the relative abundance of Firmicutes and a decrease in Bacteroidota at the phylum level and an increase in the relative abundance of Lactobacillus at the genus level. Moreover, SSW significantly increased the concentration of butyric acid. Conclusions: Combined, these data suggested that SSW increased the relative abundance of firmicutes and the level of butyric acid and restored the balance of Treg/Th17 immune axis and gut homeostasis, thus delaying the progress of UC.

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