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1.
Fitoterapia ; : 106242, 2024 Oct 05.
Article in English | MEDLINE | ID: mdl-39374706

ABSTRACT

Polygonati Rhizoma, a Chinese medicine often used in the clinic, can irritate the tongue and throat, so it must be processed before use. Polygonati Rhizoma contains a variety of chemical components, with saponins being one of the main active ingredients. Saponins can be highly irritating to human mocous membranes and have toxicity. In this study, total saponins were extracted from raw and processed Polygonati Rhizoma and detected by UPLC-Q-TOF-MS to identify their constituents. A total of 46 saponins were detected in TSRPR(total saponins of raw Polygonati Rhizoma), TSSPR(total saponins of steamed Polygonati Rhizoma) and TSWPR(total saponins of Polygonati Rhizoma steamed in wine). Of these, 9 compounds that were present in TSRPR were not detected in TSSPR and TSWPR. C.elegans was used as a model animal to study the neurotoxic effect and its mechanisms. TSRPR was found to have neurotoxic effects on C.elegans, but TSSPR and TSWPR had no adverse effects on the nematodes. The disappearance of the irritant effect of raw Polygonati Rhizoma after processing might be related to the changes in the composition of saponins, and the main reason might be the structural transformation of saponins. In particular, the sugar chains of some highly irritating saponins may have been removed or highly irritating saponins isomerized into weakly irritating saponins. The mechanisms of neurotoxic effects on C.elegans may include upregulation of ced-3 and egl-1 expression to promote apoptosis, damage to GABAergic and cholinergic neurons, downregulation of the GABA transmitter receptor genes ggr-1 and gab-1, and a decrease in glutamate levels that impairs nerve signal transmission.

2.
Article in English | MEDLINE | ID: mdl-39356052

ABSTRACT

INTRODUCTION: Our objective was to compare the performance of the first vaginal examination at 8 versus 4 h after amniotomy following Foley ripening in nulliparous labor induction. MATERIAL AND METHODS: A randomized controlled trial was conducted from June 2021 to January 2022. 210 nulliparas at term for labor induction were randomized: 105 each to first vaginal examination at 8 or 4 h after Foley balloon ripening and amniotomy. Titrated oxytocin infusion was routinely commenced after amniotomy to expedite labor. Primary outcomes were the amniotomy-to-delivery interval (non-inferiority hypothesis) and maternal satisfaction with their allocated labor care (superiority hypothesis) within 24 h after delivery. Analyses performed using t-test, Mann-Whitney U test, and Chi-squared test as appropriate. RESULTS: The amniotomy-to-delivery interval was mean ± standard deviation 8.7 ± 3.4 versus 8.4 ± 3.7, mean difference 0.4 (97.5% CI: -0.7 to 1.5) hours, p = 0.442 within the pre-specified 2-hour non-inferiority margin, and maternal satisfaction score with allocated labor care was median [interquartile range] 8[7.5-10] versus 8[7.0-10], p = 0.248 for 8 versus 4 h arms, respectively. The amniotomy to first vaginal examination intervals was 5.9 ± 2.3 versus 3.6 ± 1.0 h, p < 0.001, and the number of vaginal examinations was 2[1-2.5] versus 3 [2, 3], p < 0.001 for 8 versus 4 h, respectively. The first vaginal examination was less likely to have been performed as scheduled, more likely to be indicated by the urge to bear down, and non-reassuring cardiotocography for the 8 h arm (p < 0.001). Spontaneous vaginal delivery was significantly more likely and instrumental vaginal delivery less likely, but cesarean rate was not significantly different for the 8 h arm (p = 0.017). CONCLUSIONS: A routine first vaginal examination at 8 h compared to 4 h is non-inferior for the time to birth but does not increase maternal satisfaction although the number of vaginal examinations is fewer. The increase in spontaneous vaginal delivery and reduction in instrumental vaginal delivery rates warrant further powered primary evaluation.

3.
Opt Lett ; 49(19): 5407-5410, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-39352968

ABSTRACT

Tunable metasurfaces offer a promising avenue for dynamically modulating terahertz waves. Phase-change materials are crucial in this dynamic modulation, enabling precise and reversible control over the electromagnetic properties of the metasurfaces. In this study, we designed and experimentally fabricated a tunable lattice-induced transparent metasurface. This metasurface comprises two gold rod resonators exhibiting different periodic distributions, each supporting an electric dipole resonance at 2.03 THz and a surface lattice resonance at 1.51 THz, respectively. By combining these structures, we realize lattice-induced transparency. Simulation results show that the phase change of Ge2Sb2Te5 modulates these resonances, with the crystalline state significantly weakening their resonance strength intensity. The maximum modulation depth of the lattice-induced transparency peak can reach 44.4%. Experimental results of laser-induced GST phase changes confirm a modulation depth of 42.4%. This innovative metasurface design holds promise for applications in terahertz communication systems.

4.
Chin Med ; 19(1): 123, 2024 Sep 09.
Article in English | MEDLINE | ID: mdl-39252074

ABSTRACT

Traditional Chinese medicine (TCM) is considered to be one of the most comprehensive and influential form of traditional medicine. It plays an important role in clinical treatment and adjuvant therapy for cancer. However, the complex composition of TCM presents challenges to the comprehensive and systematic understanding of its antitumor mechanisms, which hinders further development of TCM with antitumor effects. Omics technologies can immensely help in elucidating the mechanism of action of drugs. They utilize high-throughput sequencing and detection techniques to provide deeper insights into biological systems, revealing the intricate mechanisms through which TCM combats tumors. Multi-omics approaches can be used to elucidate the interrelationships among different omics layers by integrating data from various omics disciplines. By analyzing a large amount of data, these approaches further unravel the complex network of mechanisms underlying the antitumor effects of TCM and explain the mutual regulations across different molecular levels. In this study, we presented a comprehensive overview of the recent progress in single-omics and multi-omics research focused on elucidating the mechanisms underlying the antitumor effects of TCM. We discussed the significance of omics technologies in advancing research on the antitumor properties of TCM and also provided novel research perspectives and methodologies for further advancing this research field.

5.
Small ; : e2405674, 2024 Sep 03.
Article in English | MEDLINE | ID: mdl-39225385

ABSTRACT

Si provides an effective approach to achieving high-energy batteries owing to its high energy density and abundance. However, the poor stability of Si requires buffering with graphite particles when used as anodes. Currently, commercial lithium-ion batteries with Si/graphite composite anodes can provide a high energy density and are expected to replace traditional graphite-based batteries. The different lithium storage properties of Si and graphite lead to different degrees of lithiation and chemical environments for this composite anode, which significantly affects the performance of batteries. Herein, the interplay between Si and graphite in mechanically mixed Si/graphite composite anodes is emphasized, which alters the lithiation sequence of the active materials and thus the cycling performance of the battery. Furthermore, performance optimization can be achieved by changing the intrinsic properties of the active materials and external operating conditions, which are summarized and explained in detail. The investigation of the interplay based on Si/graphite composite anodes lays the foundation for developing long-life and high-energy batteries. The abovementioned experimental methods provide logical guidance for future research on composite electrodes with multiple active materials.

6.
Elife ; 122024 Sep 13.
Article in English | MEDLINE | ID: mdl-39269442

ABSTRACT

Van Gogh-like 2 (Vangl2), a core planar cell polarity component, plays an important role in polarized cellular and tissue morphology induction, growth development, and cancer. However, its role in regulating inflammatory responses remains elusive. Here, we report that Vangl2 is upregulated in patients with sepsis and identify Vangl2 as a negative regulator of The nuclear factor-kappaB (NF-κB) signaling by regulating the protein stability and activation of the core transcription component p65. Mice with myeloid-specific deletion of Vangl2 (Vangl2ΔM) are hypersusceptible to lipopolysaccharide (LPS)-induced septic shock. Vangl2-deficient myeloid cells exhibit enhanced phosphorylation and expression of p65, therefore, promoting the secretion of proinflammatory cytokines after LPS stimulation. Mechanistically, NF-κB signaling-induced-Vangl2 recruits E3 ubiquitin ligase PDLIM2 to catalyze K63-linked ubiquitination on p65, which serves as a recognition signal for cargo receptor NDP52-mediated selective autophagic degradation. Taken together, these findings demonstrate Vangl2 as a suppressor of NF-κB-mediated inflammation and provide insights into the crosstalk between autophagy and inflammatory diseases.


Subject(s)
Autophagy , Sepsis , Signal Transduction , Transcription Factor RelA , Animals , Mice , Humans , Transcription Factor RelA/metabolism , Transcription Factor RelA/genetics , Sepsis/metabolism , NF-kappa B/metabolism , Lipopolysaccharides , Ubiquitin-Protein Ligases/metabolism , Ubiquitin-Protein Ligases/genetics , Mice, Inbred C57BL , Ubiquitination , Nerve Tissue Proteins , Adaptor Proteins, Signal Transducing , LIM Domain Proteins
7.
J Colloid Interface Sci ; 678(Pt B): 88-94, 2024 Sep 03.
Article in English | MEDLINE | ID: mdl-39241450

ABSTRACT

Considerable attention has been paid to the preparation of single-atom solid base catalysts (SASBCs) owing to their high activity and maximized utilization of basic sites. At present, the reported fabrication methods of SASBCs, such as two-step reduction strategy and sublimation capture strategy, require high temperature. Such a high activation temperature is easy to cause the sublimation loss of alkali or alkaline earth metal atoms and destructive to the support structure. Herein, a new SASBC, Ca1/UiO-67-BPY, is fabricated, in which the alkaline earth metal Ca sites are immobilized onto N-rich metal-organic framework UiO-67-BPY at room temperature. The results show that the atomic configuration of Ca single atoms is coordinated by two N atoms in the framework. The obtained Ca SASBC possesses ordered structure and exhibits high product yield of 87.2% in the Knoevenagel reaction between benzaldehyde and malononitrile. Furthermore, thanks to the Ca single atoms sites anchored on UiO-67-BPY, the Ca1/UiO-67-BPY catalyst also shows good stability during cycles. This work might offer new insight in designing SASBCs for different base-catalyzed reactions.

8.
Theranostics ; 14(15): 6016-6035, 2024.
Article in English | MEDLINE | ID: mdl-39346538

ABSTRACT

Rationale: Total hip arthroplasty (THA) and total knee arthroplasty (TKA) are effective interventions for end-stage osteoarthritis; however, periprosthetic infection is a devastating complication of arthroplasty. To safely prevent periprosthetic infection and enhance osteointegration, the surface modification strategy was utilized to kill bacteria, modulate the osteoimmune microenvironment, and improve new bone formation. Methods: We used the hydrothermal method to fabricate a bionic insect wing with the disordered titanium dioxide nanoneedle (TNN) coating. The mussel-inspired poly-dopamine (PDA) and antibacterial silver nanoparticles (AgNPs) were coated on TNN, named AgNPs-PDA@TNN, to improve the biocompatibility and long-lasting bactericidal capacity. The physicochemical properties of the engineered specimen were evaluated with SEM, AFM, XPS spectrum, and water contact assay. The biocompatibility, bactericidal ability, and the effects on macrophages and osteogenic differentiation were assessed with RT-qPCR, Western blotting, live/dead staining, immunofluorescent staining, etc. Results: The AgNPs-PDA@TNN were biocompatible with macrophages and exhibited immunomodulatory ability to promote M2 macrophage polarization. In addition, AgNPs-PDA@TNN ameliorated the cytotoxicity caused by AgNPs, promoted cell spreading, and increased osteogenesis and matrix deposition of BMSCs. Furthermore, AgNPs-PDA@TNN exhibited bactericidal ability against E. coli and S. aureus by the bionic nanostructure and coated AgNPs. Various imaging analyses indicated the enhanced bactericidal ability and improved new bone formation by AgNPs-PDA@TNN in vivo. H&E, Gram, and Masson staining, verified the improved bone formation, less inflammation, infection, and fibrosis encapsulation. The immunofluorescence staining confirmed the immunomodulatory ability of AgNPs-PDA@TNN in vivo. Conclusion: The bionic insect wing AgNPs-PDA@TNN coating exhibited bactericidal property, immunomodulatory ability, and enhanced osteointegration. Thus, this multidimensional bionic implant surface holds promise as a novel strategy to prevent periprosthetic infection.


Subject(s)
Anti-Bacterial Agents , Metal Nanoparticles , Osseointegration , Prosthesis-Related Infections , Silver , Staphylococcus aureus , Titanium , Titanium/chemistry , Titanium/pharmacology , Animals , Prosthesis-Related Infections/prevention & control , Prosthesis-Related Infections/microbiology , Mice , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Metal Nanoparticles/chemistry , Silver/pharmacology , Silver/chemistry , Staphylococcus aureus/drug effects , Osseointegration/drug effects , RAW 264.7 Cells , Macrophages/drug effects , Macrophages/immunology , Osteogenesis/drug effects , Indoles/pharmacology , Indoles/chemistry , Humans , Polymers
9.
Front Pharmacol ; 15: 1425157, 2024.
Article in English | MEDLINE | ID: mdl-39161904

ABSTRACT

Background: Breast cancer (BC) is one of the most frequently observed malignancies globally, yet drug development for BC has been encountering escalating challenges. Commiphora myrrha is derived from the dried resin of C. myrrha (T. Nees) Engl., and is widely adopted in China for treating BC. However, the anti-BC effect and underlying mechanism of C. myrrha remain largely unclear. Methods: MTT assay, EdU assay, and colony formation were used to determine the effect of C. myrrha n-hexane extract (CMHE) on the proliferation of human BC cells. Cell cycle distribution and apoptosis were assessed via flow cytometry analysis. Moreover, metastatic potential was evaluated using wound-scratch assay and matrigel invasion assay. The 4T1 breast cancer-bearing mouse model was established to evaluate the anti-BC efficacy of CMHE in vivo. RNA-sequencing analysis, quantitative real-time PCR, immunoblotting, immunohistochemical analysis, RNA interference assay, and database analysis were conducted to uncover the underlying mechanism of the anti-BC effect of CMHE. Results: We demonstrated the significant inhibition in the proliferative capability of BC cell lines MDA-MB-231 and MCF-7 by CMHE. Moreover, CMHE-induced G0/G1 phase arrest and apoptosis of the above two BC cell lines were also observed. CMHE dramatically repressed the metastatic potential of these two cells in vitro. Additionally, the administration of CMHE remarkably suppressed tumor growth in 4T1 tumor-bearing mice. No obvious toxic or side effects of CMHE administration in mice were noted. Furthermore, immunohistochemical (IHC) analysis demonstrated that CMHE treatment inhibited the proliferative and metastatic abilities of cancer cells, while also promoting apoptosis in the tumor tissues of mice. Based on RNA sequencing analysis, quantitative real-time PCR, immunoblotting, and IHC assay, the administration of CMHE downregulated Cyclin D1/CDK4-Rb signaling pathway in BC. Furthermore, RNA interference assay and database analysis showed that downregulated Cyclin D1/CDK4 signaling cascade participated in the anti-BC activity of CMHE. Conclusion: CMHE treatment resulted in the suppression of BC cell growth through the stimulation of cell cycle arrest at the G0/G1 phase and the induction of apoptotic cell death via the inhibition of the Cyclin D1/CDK4-Rb pathway, thereby enhancing the anti-BC effect of CMHE. CMHE has potential anti-BC effects, particularly in those harboring aberrant activation of Cyclin D1/CDK4-Rb signaling.

10.
ACS Appl Mater Interfaces ; 16(32): 42321-42331, 2024 Aug 14.
Article in English | MEDLINE | ID: mdl-39088694

ABSTRACT

Aqueous rechargeable batteries are regarded as one of the most reliable solutions for electrochemical energy storage, and ion (e.g., H+ or OH-) transport is essential for their electrochemical performance. However, modeling and numerical simulations often fall short of depicting the actual ion transport characteristics due to deviations in model assumptions from reality. Experimental methods, including laser interferometry, Raman, and nuclear magnetic resonance imaging, are limited by the complexity of the system and the restricted detection of ions, making it difficult to detect specific ions such as H+ and OH-. Herein, in situ visualization of ion transport is achieved by innovatively introducing laser scanning confocal microscopy. Taking neutral Zn-air batteries as an example and using a pH-sensitive probe, real-time dynamic pH changes associated with ion transport processes are observed during battery operation. The results show that after immersion in the zinc sulfate electrolyte, the pH near the Zn electrode changes significantly and pulsation occurs, which demonstrates the intense self-corrosion hydrogen evolution reaction and the periodic change in the reaction intensity. In contrast, the change in the pH of the galvanized electrode plate is weak, proving its significant corrosion inhibition effect. For the air electrode, the heterogeneity of ion transport during the discharging and charging process is presented. With an increase of the current density, the ion transport characteristics gradually evolve from diffusion dominance to convection-diffusion codominance, revealing the importance of convection in the ion transport process inside batteries. This method opens up a new approach of studying ion transport inside batteries, guiding the design for performance enhancement.

11.
Cell Signal ; 123: 111338, 2024 Nov.
Article in English | MEDLINE | ID: mdl-39117252

ABSTRACT

BACKGROUND: PDAC, also known as pancreatic ductal adenocarcinoma, is often diagnosed at a late stage due to nonspecific symptoms and a distinct lack of reliable biomarkers for timely diagnosis. Ferroptosis, a novel non-apoptotic cell death mode discovered in recent years, is strongly linked to the progression of PDAC and the evasion of the immune system. The objective of this study is to discover a novel ceRNA biomarker associated with ferroptosis and investigate its possible molecular mechanisms and therapeutic potential in PDAC. METHODS: Based on the FerrDb and TCGA databases, the R survival package was used to screen for ferroptosis-related mRNAs associated with PDAC prognosis. The ferroptosis-related ceRNA network was identified by miRTarBase, miRNet, and starBase and visualized using Cytoscape. The LASSO regression analysis was used to build a risk model associated with ceRNA. Additionally, we investigated the correlation between the ceRNA axis and the infiltration of immune cells in PDAC by employing the ssGSEA algorithm. Spearman correlation analysis was used to investigate the association between the ceRNA network and the expression levels of immune checkpoint genes in PDAC. The prediction of potential medications for PAAD patients with high risk scores was conducted using the R package oncoPredict and the Genomics of Drug Sensitivity in Cancer (GDSC) repository. Expression levels of LINC02535 in clinical specimens and PDAC cell lines were determined using qRT-PCR. CCK-8, colony formation, EdU, wound healing, and transwell assays were performed to assess the impact of reducing LINC02535 on the growth, migration, and invasion of PDAC cell lines BxPC3 and PANC1. RESULTS: We first discovered a new LINC02535/miR-30c-5p/EIF2S1 axis associated with ferroptosis and created a prognostic nomogram for predicting overall survival. Meanwhile, the risk scores of the LINC02535/miR-30c-5p/EIF2S1 axis associated with ferroptosis were linked to immune subtypes in PDAC. The high immune infiltration subtype exhibited elevated ceRNA risk scores and EIF2S1 expression. The correlation analysis revealed a positive correlation between ceRNA risk scores and four immune cells, namely Activated CD4 T cell, Memory B cell, Neutrophil, and Type 2 T helper cell, as well as four immune checkpoint genes, namely CD274, HAVCR2, PDCD1LG2, and TIGIT. The analysis of drug sensitivity indicated that individuals with a high-risk score may exhibit greater sensitivity to inhibitors targeting MEK1/2 compared to those with a low-risk score. In our validation experiments, it was observed that the expression of LINC02535 was increased in both PDAC tissues and cell lines. Additionally, the inhibition of LINC02535 resulted in decreased proliferation, migration, and invasion of PDAC cells. Rescue experiments demonstrated that LINC02535 promoted PDAC cell growth and metastasis by upregulating EIF2S1 expression. CONCLUSION: To summarize, a novel ferroptosis-associated LINC02535/miR-30c-5p/EIF2S1 ceRNA network for PDAC patients was established. The analysis of this network's functionality offers potential insights for clinical decision-making and the advancement of precision medicine.


Subject(s)
Biomarkers, Tumor , Carcinoma, Pancreatic Ductal , Ferroptosis , Gene Expression Regulation, Neoplastic , MicroRNAs , Pancreatic Neoplasms , RNA, Long Noncoding , Humans , Ferroptosis/genetics , MicroRNAs/metabolism , MicroRNAs/genetics , Biomarkers, Tumor/metabolism , Biomarkers, Tumor/genetics , Prognosis , Carcinoma, Pancreatic Ductal/genetics , Carcinoma, Pancreatic Ductal/pathology , Carcinoma, Pancreatic Ductal/metabolism , Carcinoma, Pancreatic Ductal/immunology , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Disease Progression , Cell Line, Tumor
12.
Int Immunopharmacol ; 140: 112898, 2024 Oct 25.
Article in English | MEDLINE | ID: mdl-39128417

ABSTRACT

OBJECTIVE: Disorders of lipid oxidation play an important role in organ damage, and lipid metabolites are associated with inflammation and coagulation dysfunction in sepsis. However, the specific molecular mechanism by which lipid metabolism-related proteins regulate sepsis is still unclear. The aim of this study is to investigate the role of mortality factor 4-like protein 1 (MORF4L1, also called MRG15), a hepatic lipid metabolism related gene, in sepsis-induced liver injury. METHODS: In the mouse sepsis models established by cecal ligation and puncture (CLP) and lipopolysaccharide (LPS), the impact of pretreatment with the MRG15 inhibitor argatroban on sepsis-related liver injury was investigated. In the LPS-induced hepatocyte sepsis cell model, the effects of MRG15 overexpression or knockdown on hepatic inflammation and lipid metabolism were studied. Additionally, in a co-culture system of hepatocytes and macrophages, the influence of MRG15 knockdown in hepatocytes on the synthesis and secretion of inflammation-related protein PCSK9 as well as its effect on macrophage activation were examined. RESULTS: Studies have shown that MRG15 expression was increased in septicemia mice and positively correlated with lipid metabolism and inflammation. However, knockdown of MRG15 ameliorates sepsis-induced hepatocyte injury. Increased MRG15 in LPS-stimulated hepatocytes promotes PCSK9 synthesis and secretion, which induces macrophage M1 polarization and exacerbates the inflammatory response. Agatroban, an inhibitor of MRG15, ameliorates sepsis-induced liver injury in mice by inhibiting MRG15-induced lipid metabolism disorders and inflammatory responses. CONCLUSIONS: In sepsis, increased MRG15 expression in hepatocytes leads to disturbed hepatic lipid metabolism and induces macrophage M1 polarization by secreting PCSK9, ultimately exacerbating liver injury.


Subject(s)
Hepatocytes , Lipid Metabolism , Lipopolysaccharides , Proprotein Convertase 9 , Sepsis , Sulfonamides , Animals , Humans , Male , Mice , Arginine/analogs & derivatives , Arginine/metabolism , Disease Models, Animal , Hepatocytes/metabolism , Liver/pathology , Liver/metabolism , Macrophage Activation , Macrophages/metabolism , Macrophages/immunology , Mice, Inbred C57BL , Pipecolic Acids/pharmacology , Proprotein Convertase 9/metabolism , Proprotein Convertase 9/genetics , RAW 264.7 Cells , Sepsis/metabolism , Sulfonamides/pharmacology
13.
Sci Bull (Beijing) ; 69(16): 2491-2495, 2024 Aug 30.
Article in English | MEDLINE | ID: mdl-38972806
14.
mLife ; 3(2): 251-268, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38948143

ABSTRACT

Broad-spectrum antibacterial drugs often lack specificity, leading to indiscriminate bactericidal activity, which can disrupt the normal microbial balance of the host flora and cause unnecessary cytotoxicity during systemic administration. In this study, we constructed a specifically targeted antimicrobial peptide against Staphylococcus aureus by introducing a phage-displayed peptide onto a broad-spectrum antimicrobial peptide and explored its structure-function relationship through one-factor modification. SFK2 obtained by screening based on the selectivity index and the targeting index showed specific killing ability against S. aureus. Moreover, SFK2 showed excellent biocompatibility in mice and piglet, and demonstrated significant therapeutic efficacy against S. aureus infection. In conclusion, our screening of phage-derived heptapeptides effectively enhances the specific bactericidal ability of the antimicrobial peptides against S. aureus, providing a theoretical basis for developing targeted antimicrobial peptides.

15.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 40(6): 501-507, 2024 Jun.
Article in Chinese | MEDLINE | ID: mdl-38952089

ABSTRACT

Objective To investigate the effects of astragaloside IV(AS-IV) on the balance of T helper type 1 (Th1) and Th2 cells in mice with IgA nephropathy (IgAN) and its possible mechanism. Methods The IgAN model of BALB/c mice was established. Successfully modeled mice were randomly divided into four groups: model, AS-IV low dose, AS-IV medium dose and AS-IV high dose groups, with 10 mice in each group. Another 10 mice served as the control group. Mice in the low, medium and high dose groups were administered 12.5, 25 and 50 mg/kg AS-IV suspension (prepared in normal saline) by gavage, while the control and model groups were given an equivalent volume of normal saline. The 24-hour urinary protein (24 h UPr) content and urine red blood cell count were measured in each group. The levels of blood urea nitrogen (BUN), serum creatinine (Scr) and albumin (ALB) were determined. Serum interferon γ (IFN-γ), interleukin 4 (IL-4) and IL-10 levels were detected by ELISA. The ratio of Th1/Th2 cells in peripheral blood of mice was detected using flow cytometry. Histopathological changes in the kidney of mice were observed by HE staining. RT-PCR and Western blot were used to detect the mRNA and protein expressions of T cell immunoglobulin and mucin domain gene 1 (TIM-1), Toll-like receptor 4 (TLR4) in mouse kidney tissue. Results Compared with the model group, in weeks 12 and 15, the urine red blood cell count, 24 h UPr, BUN, Scr, levels of IL-4 and IL-10, the proportion of Th2 cells, as well as the mRNA and protein expression levels of TIM-1 and TLR4 were significantly decreased in the low, medium and high dose groups of AS-IV, and the levels of ALB, IFN-γ, the proportion of Th1 cells and Th1/Th2 cell ratio were increased, with the high-dose group showing the best effects. Conclusion AS-IV can inhibit TIM-1 signaling pathway, increase the Th1/Th2 cell ratio, inhibit the inflammatory reaction, and alleviate the renal injury in IgAN mice.


Subject(s)
Glomerulonephritis, IGA , Hepatitis A Virus Cellular Receptor 1 , Mice, Inbred BALB C , Saponins , Signal Transduction , Th1 Cells , Th2 Cells , Triterpenes , Animals , Hepatitis A Virus Cellular Receptor 1/metabolism , Hepatitis A Virus Cellular Receptor 1/genetics , Triterpenes/pharmacology , Glomerulonephritis, IGA/drug therapy , Glomerulonephritis, IGA/metabolism , Glomerulonephritis, IGA/immunology , Saponins/pharmacology , Th1 Cells/drug effects , Th1 Cells/immunology , Th1 Cells/metabolism , Signal Transduction/drug effects , Th2 Cells/drug effects , Th2 Cells/immunology , Th2 Cells/metabolism , Mice , Toll-Like Receptor 4/metabolism , Toll-Like Receptor 4/genetics , Interleukin-4/genetics , Interleukin-4/metabolism , Kidney/drug effects , Kidney/pathology , Kidney/metabolism , Interleukin-10/genetics , Interleukin-10/metabolism , Interferon-gamma/metabolism , Interferon-gamma/genetics , Male , Female
16.
BMC Pregnancy Childbirth ; 24(1): 461, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38965486

ABSTRACT

BACKGROUND: Maternal Group B Streptococcus (GBS) colonization is influenced by many factors but results are inconsistent. Consideration of antenatal risk factors may help inform decision making on GBS microbiological culture screening where universal screening is not standard of care. We sought to identify independent predictors of GBS colonization at 34-37 weeks gestation incorporating vaginal symptoms, perineal hygiene measures, sexual activity, and a potential novel factor, constipation. METHODS: In this prospective cross-sectional study, 573 women at 34-37 weeks gestation had an ano-vaginal swab taken and sent for selective culture for GBS. Women were asked about vaginal bleeding, discharge, irritation and candidiasis, antibiotic use during pregnancy, ano-vaginal hygiene practices such as douching and perineal cleansing after toileting, sexual intercourse related activities, and a potential novel factor for GBS carriage, constipation. Maternal basic demographics and obstetric-related characteristics were also collected. Bivariate analyses were performed to identify associates of GBS colonization. All variables with p < 0.05 found on bivariate analysis were then included into a model for multivariable binary logistic regression analysis to identify independent risk factors for GBS colonization. RESULTS: GBS colonization was found in 235/573 (41.0%) of participants. Twenty six independent variables were considered for bivariate analysis. Eight were found to have p < 0.05. Following adjusted analysis, six independent predictors of GBS colonization were identified: ethnicity, previous neonatal GBS prophylaxis, antenatal vaginal irritation, antibiotic use, recent panty liner use, and frequency of sexual intercourse. Vaginal discharge and perineal cleansing were not associated after adjustment. Recent douching and constipation were not associated on bivariate analysis. CONCLUSION: The identification of independent predictors of GBS colonization in late pregnancy may inform the woman and care provider in their shared decision making for microbiological screening at 35-38 weeks gestation in locations where universal GBS screening is not standard of care. ETHICS OVERSIGHT: This study was approved by the Medical Ethics Committee of University Malaya Medical Centre (UMMC) on August 9, 2022, reference number 2022328-11120.


Subject(s)
Constipation , Hygiene , Perineum , Pregnancy Complications, Infectious , Sexual Behavior , Streptococcal Infections , Streptococcus agalactiae , Vagina , Humans , Female , Pregnancy , Prospective Studies , Streptococcus agalactiae/isolation & purification , Adult , Constipation/microbiology , Constipation/prevention & control , Vagina/microbiology , Cross-Sectional Studies , Pregnancy Complications, Infectious/microbiology , Pregnancy Complications, Infectious/prevention & control , Pregnancy Complications, Infectious/diagnosis , Streptococcal Infections/prevention & control , Streptococcal Infections/diagnosis , Perineum/microbiology , Perineum/injuries , Risk Factors , Anal Canal/microbiology , Pregnancy Trimester, Third
18.
Chemosphere ; 361: 142517, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38830464

ABSTRACT

Indoor volatile formaldehyde is a serious health hazard. The development of low-temperature and efficient nonhomogeneous oxidation catalysts is crucial for protecting human health and the environment but is also quite challenging. Single-atom catalysts (SACs) with active centers and coordination environments that are precisely tunable at the atomic level exhibit excellent catalytic activity in many catalytic fields. Among two-dimensional materials, the nonmagnetic monolayer material g-C3N4 may be a good platform for loading single atoms. In this study, the effect of nitrogen defect formation on the charge distribution of g-C3N4 is discussed in detail using density functional theory (DFT) calculations. The effect of nitrogen defects on the activated molecular oxygen of Pt/C3N4 was systematically revealed by DFT calculations in combination with molecular orbital theory. Two typical reaction mechanisms for the catalytic oxidation of formaldehyde were proposed based on the Eley-Rideal (E-R) mechanism. Pt/C3N4-V3N was more advantageous for path 1, as determined by the activation energy barrier of the rate-determining step and product desorption. Finally, the active centers and chemical structures of Pt/C3N4 and Pt/C3N4-V3N were verified to have good stability at 375 K by determination of the migration energy barriers and ab initio molecular dynamics simulations. Therefore, the formation of N defects can effectively anchor single-atom Pt and provide additional active sites, which in turn activate molecular oxygen to efficiently catalyze the oxidation of formaldehyde. This study provides a better understanding of the mechanism of formaldehyde oxidation by single-atom Pt catalysts and a new idea for the development of Pt as well as other metal-based single-atom oxidation catalysts.


Subject(s)
Density Functional Theory , Formaldehyde , Oxidation-Reduction , Platinum , Formaldehyde/chemistry , Catalysis , Platinum/chemistry , Nitrogen Compounds/chemistry , Molecular Dynamics Simulation , Oxygen/chemistry , Graphite
19.
Int J Mol Sci ; 25(11)2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38892371

ABSTRACT

The composition of skeletal muscle fiber types affects the quality of livestock meat and human athletic performance and health. L-arginine (Arg), a semi-essential amino acid, has been observed to promote the formation of slow-twitch muscle fibers in animal models. However, the precise molecular mechanisms are still unclear. This study investigates the role of Arg in skeletal muscle fiber composition and mitochondrial function through the mTOR signaling pathway. In vivo, 4-week C56BL/6J male mice were divided into three treatment groups and fed a basal diet supplemented with different concentrations of Arg in their drinking water. The trial lasted 7 weeks. The results show that Arg supplementation significantly improved endurance exercise performance, along with increased SDH enzyme activity and upregulated expression of the MyHC I, MyHC IIA, PGC-1α, and NRF1 genes in the gastrocnemius (GAS) and quadriceps (QUA) muscles compared to the control group. In addition, Arg activated the mTOR signaling pathway in the skeletal muscle of mice. In vitro experiments using cultured C2C12 myotubes demonstrated that Arg elevated the expression of slow-fiber genes (MyHC I and Tnnt1) as well as mitochondrial genes (PGC-1α, TFAM, MEF2C, and NRF1), whereas the effects of Arg were inhibited by the mTOR inhibitor rapamycin. In conclusion, these findings suggest that Arg modulates skeletal muscle fiber type towards slow-twitch fibers and enhances mitochondrial functions by upregulating gene expression through the mTOR signaling pathway.


Subject(s)
Arginine , Muscle Fibers, Skeletal , Signal Transduction , TOR Serine-Threonine Kinases , Animals , TOR Serine-Threonine Kinases/metabolism , Signal Transduction/drug effects , Mice , Arginine/metabolism , Arginine/pharmacology , Male , Muscle Fibers, Skeletal/metabolism , Muscle Fibers, Skeletal/drug effects , Mice, Inbred C57BL , Muscle Fibers, Slow-Twitch/metabolism , Muscle Fibers, Slow-Twitch/drug effects , Muscle, Skeletal/metabolism , Muscle, Skeletal/drug effects , Cell Line
20.
Sci Rep ; 14(1): 14307, 2024 06 21.
Article in English | MEDLINE | ID: mdl-38906931

ABSTRACT

Breast cancer (BC) remains a significant health concern for women globally, prompting the relentless pursuit of novel therapeutic modalities. As a traditional Chinese medicine, Boswellia carterii has been extensively used to treat various cancers, such as BC. However, the anti-BC effect and underlying mechanism of Boswellia carterii remain largely unclear. The aim of this study is to explore the therapeutic effect of Boswellia carterii n-hexane extract (BCHE) against BC as well as its underlying mechanism. The present study showed that BCHE significantly suppressed the viability of human BC cells. Moreover, BCHE exhibited potent anti-BC activity in vivo with no significant toxic effects. Additionally, BCHE induced ferroptosis via increased Transferrin expression and the intracellular accumulation of Fe2+, as well as decreased glutathione peroxidase 4 (GPX4) expression and the upregulation of reactive oxygen species (ROS)-induced lipid peroxidation in BC cells. In vivo experimental results also demonstrated that BCHE effectively induced ferroptosis through GPX4 downregulation and Transferrin upregulation in tumor-bearing mice. Overall, BCHE inhibited the growth of BC cells by inducing ferroptosis mediated by modulating the iron accumulation pathway and the lipid peroxidation pathway. Therefore, BCHE could serve as a potential ferroptosis-targeting drug for treating BC.


Subject(s)
Boswellia , Breast Neoplasms , Ferroptosis , Phospholipid Hydroperoxide Glutathione Peroxidase , Plant Extracts , Transferrin , Ferroptosis/drug effects , Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism , Humans , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Female , Animals , Transferrin/metabolism , Mice , Plant Extracts/pharmacology , Plant Extracts/chemistry , Cell Line, Tumor , Boswellia/chemistry , Reactive Oxygen Species/metabolism , Xenograft Model Antitumor Assays , Cell Proliferation/drug effects , Hexanes/chemistry , Down-Regulation/drug effects , Lipid Peroxidation/drug effects , Up-Regulation/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Mice, Nude , Mice, Inbred BALB C
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