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1.
J Ethnopharmacol ; 336: 118717, 2025 Jan 10.
Article in English | MEDLINE | ID: mdl-39181284

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Thrombosis is a common cause of morbidity and mortality worldwide. Lagopsis supina (Stephan ex Willd.) Ikonn.-Gal. ex Knorring is an ancient Chinese herbal medicine used for treating thrombotic diseases. Nevertheless, the antithrombotic mechanisms and effective constituents of this plant have not been clarified. AIM OF THE STUDY: This work aimed to elucidate the pharmacodynamics and mechanism of L. supina against thrombosis. MATERIALS AND METHODS: Systematic network pharmacology was used to explore candidate effective constituents and hub targets of L. supina against thrombosis. Subsequently, the binding affinities of major constituents with core targets were verified by molecular docking analysis. Afterward, the therapeutic effect and mechanism were evaluated in an arteriovenous bypass thrombosis rat model. In addition, the serum metabolomics analysis was conducted using ultra-high performance liquid chromatography coupled with Q-Exactive mass spectrometry. RESULTS: A total of 124 intersected targets of L. supina against thrombosis were predicted. Among them, 24 hub targets were obtained and their mainly associated with inflammation, angiogenesis, and thrombosis approaches. Furthermore, 9 candidate effective constituents, including (22E,24R)-5α,8α-epidioxyergosta-6,22-dien-3ß-ol, aurantiamide, (22E,24R)-5α,8α-epidioxyergosta-6,9 (11),22-trien-3ß-ol, lagopsinA, lagopsin C, 15-epi-lagopsin C, lagopsin D, 15-epi-lagopsin D, and lagopsin G in L. supina and 6 potential core targets (TLR-4, TNF-α, HIF-1α, VEGF-A, VEGFR-2, and CLEC1B) were acquired. Then, these 9 constituents demonstrated strong binding affinities with the 6 targets, with their lowest binding energies were all less than -5.0 kcal/mol. The antithrombotic effect and potential mechanisms of L. supina were verified, showing a positively associated with the inhibition of inflammation (TNF-α, IL-1ß, IL-6, IL-8, and IL-10) and coagulation cascade (TT, APTT, PT, FIB, AT-III), promotion of angiogenesis (VEGF), suppression of platelet activation (TXB2, 6-keto-PGF1α, and TXB2/6-keto-PGF1α), and prevention of fibrinolysis (t-PA, u-PA, PAI-1, PAI-1/t-PA, PAI-1/u-PA, and PLG). Finally, 14 endogenous differential metabolites from serum samples of rats were intervened by L. supina based on untargeted metabolomics analysis, which were closely related to amino acid metabolism, inflammatory and angiogenic pathways. CONCLUSION: Our integrated strategy based on network pharmacology, molecular docking, metabolomics, and in vivo experiments revealed for the first time that L. supina exerts a significant antithrombotic effect through the inhibition of inflammation and coagulation cascade, promotion of angiogenesis, and suppression of platelet activation. This paper provides novel insight into the potential of L. supina as a candidate agent to treat thrombosis.


Subject(s)
Fibrinolytic Agents , Metabolomics , Molecular Docking Simulation , Network Pharmacology , Rats, Sprague-Dawley , Thrombosis , Animals , Fibrinolytic Agents/pharmacology , Fibrinolytic Agents/chemistry , Fibrinolytic Agents/isolation & purification , Rats , Male , Thrombosis/drug therapy , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/chemistry
2.
Eur Heart J Case Rep ; 8(8): ytae413, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39219803

ABSTRACT

Background: The occurrence of type A aortic dissection (TAAD) during transoesophageal echocardiography (TEE) has only been reported once. We present another case of pre-procedural type B AD with retrograde TAAD or de novo TAAD during the TEE procedure. Case summary: An 81-year-old man with a pre-existing infrarenal abdominal aortic aneurysm and highly tortuous aorta was referred to our ward for acute decompensated heart failure (ADHF) with New York Heart Association functional class II. On hospital Day 2, the patient complained of intermittent dull pain over chest and back; ADHF or acute coronary syndrome was suspected. On Day 3, we transferred the patient to the intensive care unit due to ADHF with cardiogenic shock attributed to fluid overload, atrial fibrillation with rapid ventricular response, and severe mitral regurgitation with severely impaired left ventricular ejection fraction. Given the heightened surgical risk, TEE was performed to evaluate the eligibility of mitral transcatheter edge-to-edge repair. The first mid-oesophageal long-axis view showed no evidence of dissection. After 20 min, the same view showed the occurrence of TAAD. Urgent contrast CT confirmed a TAAD extending from the aortic root to the infrarenal abdominal aorta. Due to the prohibitive risk for surgical repair of TAAD, the patient received palliative care and unfortunately passed away on hospital Day 6. Discussion: Albeit rare, TAAD could progress or de novo occur during TEE, especially in high-risk patients. Therefore, high alertness during TEE procedures is imperative. Moreover, in patients with AD and poor renal function, the risk of using TEE as an alternative diagnostic modality should be carefully considered.

3.
World J Hepatol ; 16(8): 1167-1176, 2024 Aug 27.
Article in English | MEDLINE | ID: mdl-39221094

ABSTRACT

BACKGROUND: Neoadjuvant chemotherapy can cause hepatic sinusoidal obstruction syndrome (SOS) in patients with colorectal cancer liver metastases and increases postoperative morbidity and mortality. AIM: To evaluate T1 mapping based on gadoxetic acid-enhanced magnetic resonance imaging (MRI) for diagnosis of hepatic SOS induced by monocrotaline. METHODS: Twenty-four mice were divided into control (n = 10) and experimental (n = 14) groups. The experimental groups were injected with monocrotaline 2 or 6 days before MRI. MRI parameters were: T1 relaxation time before enhancement; T1 relaxation time 20 minutes after enhancement (T1post); a reduction in T1 relaxation time (△T1%); and first enhancement slope percentage of the liver parenchyma (ESP). Albumin and bilirubin score was determined. Histological results served as a reference. Liver parenchyma samples from the control and experimental groups were analyzed by western blotting, and organic anion transporter polypeptide 1 (OATP1) was measured. RESULTS: T1post, △T1%, and ESP of the liver parenchyma were significantly different between two groups (all P < 0.001) and significantly correlated with the total histological score of hepatic SOS (r = -0.70, 0.68 and 0.79; P < 0.001). △T1% and ESP were positively correlated with OATP1 levels (r = 0.82, 0.85; P < 0.001), whereas T1post had a negative correlation with OATP1 levels (r = -0.83; P < 0.001). CONCLUSION: T1 mapping based on gadoxetic acid-enhanced MRI may be useful for diagnosis of hepatic SOS, and MRI parameters were associated with OATP1 levels.

4.
Angew Chem Int Ed Engl ; : e202414202, 2024 Sep 11.
Article in English | MEDLINE | ID: mdl-39261287

ABSTRACT

Single-atom catalysts with maximal atom-utilization have emerged as promising alternatives for chlorine evolution reaction (CER) toward valuable Cl2 production. However, understanding their intrinsic CER activity have so far been plagued due to the lack of well-defined atomic structure controlling. Herein, we prepare and identify a series of atomically dispersed noble metals (e.g., Pt, Ir, Ru) in nitrogen-doped nanocarbons (M1-N-C) with an identical M-N4 moiety, which allows objective activity evaluation. Electrochemical experiments, operando Raman spectroscopy, and quasi-in situ electron paramagnetic resonance spectroscopy analyses collectively reveal that all the three M1-N-C proceed the CER via a direct Cl-mediated Vomer-Heyrovský mechanism with reactivity following the trend of Pt1-N-C > Ir1-N-C > Ru1-N-C. Density functional theory (DFT) calculations reveal that this activity trend is governed by the binding strength of Cl*-Cl intermediate (ΔGCl*-Cl) on M-N4 sites (Pt < Ir < Ru) featuring distinct d-band centers, providing a reliable thermodynamic descriptor for rational design of single metal sites toward Cl2 electrosynthesis.

5.
Mol Biomed ; 5(1): 37, 2024 Sep 10.
Article in English | MEDLINE | ID: mdl-39251538

ABSTRACT

The combination of anti-angiogenic drugs and immune checkpoint inhibitors (ICIs) in the treatment of tumors is emerging as a way to improve ICIs-resistant tumor therapy. In addition, gut microbes (GMs) are involved in angiogenesis in the tumor microenvironment and are also associated with the antitumor function of immune checkpoint inhibitors. However, it is unclear whether gut microbes have a role in anti-tumor function in the combination of anti-angiogenic drugs and immune checkpoint inhibitors for cancer treatment. Endostatin, an angiogenesis inhibitor, has been widely used as an antiangiogenic therapy for cancer. We showed that combined therapy with an adenovirus encoding human endostatin, named Ad-E, and PD-1 blockade dramatically abrogated MC38 tumor growth. The structure of intestinal microbes in mice was changed after combination treatment. We found that the antitumor function of combination therapy was inhibited after the elimination of intestinal microbes. In mice with depleted microbiota, oral gavage of Bacteroides fragilis salvaged the antitumor effects of combination Ad-E and αPD-1 monoclonal antibody (mAb) to a certain extent. Further, Bacteroides fragilis could improve CD3+T cells, NK cells, and IFNγ+CD8+ T cells in the tumor microenvironment to inhibit tumor growth. Besides, Bacteroides fragilis might restore antitumor function by down-regulating isobutyric acid (IBA). Our results suggested that GMs may be involved in the combination of Ad-E and αPD-1 mAb for cancer treatment, which has oncological implications for tumor growth dynamics and cancer immune surveillance.


Subject(s)
Colorectal Neoplasms , Endostatins , Gastrointestinal Microbiome , Immune Checkpoint Inhibitors , Programmed Cell Death 1 Receptor , Animals , Gastrointestinal Microbiome/drug effects , Endostatins/pharmacology , Endostatins/therapeutic use , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Programmed Cell Death 1 Receptor/immunology , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/immunology , Colorectal Neoplasms/microbiology , Colorectal Neoplasms/pathology , Mice , Immune Checkpoint Inhibitors/pharmacology , Immune Checkpoint Inhibitors/administration & dosage , Immune Checkpoint Inhibitors/therapeutic use , Humans , Cell Line, Tumor , Tumor Microenvironment/drug effects , Tumor Microenvironment/immunology , Mice, Inbred C57BL , Angiogenesis Inhibitors/pharmacology , Angiogenesis Inhibitors/therapeutic use , Angiogenesis Inhibitors/administration & dosage , Female
6.
Hematology ; 29(1): 2399361, 2024 Dec.
Article in English | MEDLINE | ID: mdl-39263910

ABSTRACT

OBJECTIVE: The α-globin fusion gene between the HBA2 and HBAP1 genes, is clinically important in thalassemia screening because this fusion gene can cause severe hemoglobin (Hb) H disease when combined with α0 -thalassemia (α0 -thal). In this study, we evaluate the red blood cell parameters of α-thalassemia fusion gene in southern China. METHOD: Study samples suspected of α-thalassemia fusion gene were collected and confirmed by PCR-sequencing from one medical lab center in southern China. Their genotypes and phenotypes were analyzed. RESULTS: A total of 266 cases of α-thalassemia fusion gene were confirmed in our lab from 2017 to 2023, most of them were from Hainan province (169 cases) and Huadu district of Guangzhou (21 cases), the nationality of 143 cases from Hainan was identified, with 71.3% (102/143) being from the Li minority. The Hb, MCV, MCH for αα/(αα)fusion in adult males were 143.5±11.83g/L, 81.51±4.39 fl, and 26.26±1.29 pg, respectively; and in females, they were 126.69±12.89 g/L, 80.10±4.05 fl, 25.8±2.04 pg, respectively. All 12 cases (αα) Fusion/ --SEA showed anemia with decreased Hb, MCV and MCH. CONCLUSION: The carriers of α-globin fusion gene heterozygotes are clinically silent and exhibit an α+ phenotype. Individuals with (αα)Fusion/--SEA show apparent anemia. This α-globin fusion gene is relatively common in southern China, specifically among the Li minority of Hainan province. Therefore, it should be taken into account for genetic counseling purposes.


Subject(s)
Genotype , Phenotype , alpha-Thalassemia , Humans , alpha-Thalassemia/genetics , alpha-Thalassemia/epidemiology , Male , Female , China/epidemiology , Adult , alpha-Globins/genetics , Middle Aged , Child , Adolescent , Young Adult
7.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 46(4): 581-591, 2024 Aug.
Article in Chinese | MEDLINE | ID: mdl-39223023

ABSTRACT

Vigilance is a sensitive ability to respond to small changes in the environment and it is a major component of various cognitive performance tasks.Professionals in a variety of fields require high physical and vigilance performance during the working process to ensure productivity,workplace safety,and their own safety. This article reviews the research progress in vigilance in terms of the examination methods,influencing factors,and drug treatment in recent years,aiming to improve the understanding of vigilance and provide support for the research on vigilance and clinical treatment of vigilance-related dysfunctions.


Subject(s)
Attention , Humans
8.
Food Res Int ; 194: 114927, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39232539

ABSTRACT

In this study, the potential mechanism of aroma loss in non-smoked bacon due to excessive hot air drying (beyond 24 h) was investigated, focusing on protein conformational changes and the inhibition of heme protein-mediated lipid oxidation by oleic acid. The results showed that prolonged hot-air drying caused a stretching of the myofibrillar protein (MP) conformation in bacon before 36 h, leading to an increase in reactive sulfhydryl groups, surface hydrophobicity, and the exposure of additional hydrophobic sites. Consequently, the binding ability of MP to the eight key aroma compounds (hexanal, 1-octen-3-ol, (E)-2-nonenal, 3-methyl-butanoic acid, 2-undecenal, (E, E)-2,4-decadienal, 2,3-octanedione, and dihydro-5-pentyl-2(3H)-furanone) was enhanced, resulting in their retention. On the other hand, a sustained increase in oleic acid levels has been demonstrated to effectively inhibit heme protein-mediated lipid oxidation and the formation of these key aroma compounds. Using lipidomic techniques, 30 lipid molecules were identified as potential precursors of oleic acid during the bacon drying process. Among these precursors, triglycerides (16:0/18:0/18:1) may be the most significant.


Subject(s)
Hot Temperature , Odorants , Odorants/analysis , Desiccation/methods , Meat Products/analysis , Oleic Acid/chemistry , Food Handling/methods , Hydrophobic and Hydrophilic Interactions , Protein Conformation , Volatile Organic Compounds/analysis , Volatile Organic Compounds/chemistry , Oxidation-Reduction , Aldehydes/analysis , Aldehydes/chemistry
9.
Nat Prod Res ; : 1-8, 2024 Sep 03.
Article in English | MEDLINE | ID: mdl-39225394

ABSTRACT

A new steroid named persteroid (1) and seven known compounds (2-8) were isolated from the marine-derived fungus Penicillium sp. ZYX-Z-143. The structure of 1 was determined by HRESIMS, NMR, and ECD calculations. Compound 1 showed inhibitory activity against protein tyrosine phosphatase 1B (PTP1B) with IC50 value of 46.31 ± 0.52 µM. Moreover, compound 1 potently suppressed nitric oxide (NO) production on lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. The cytotoxicity and antibacterial activity of all isolates were tested.

10.
Urol Int ; : 1-10, 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39236682

ABSTRACT

Urinary system stones are a common clinical disease, with significant differences in incidence and recurrence rates between different countries and regions. The etiology and pathogenesis of urinary system stones have not been fully elucidated, but many studies have found that some bacteria and fungi that are difficult to detect in urine constitute a unique urinary microbiome. This special urinary microbiome is closely related to the occurrence and development of urinary system stones. By analyzing the urinary microbiome and its metabolic products, early diagnosis and treatment of urinary system stones can be carried out. This article reviews the relationship between the urinary microbiome and urinary system stones, discusses the impact of the microbiome on the formation of urinary system stones and its potential therapeutic value, with the aim of providing a reference for the early diagnosis, prevention, and treatment of urinary system stones.

11.
Urolithiasis ; 52(1): 126, 2024 Sep 06.
Article in English | MEDLINE | ID: mdl-39237840

ABSTRACT

Kidney Stone Disease (KSD) constitutes a multifaceted disorder, emerging from a confluence of environmental and genetic determinants, and is characterized by a high frequency of occurrence and recurrence. Our objective is to elucidate potential causative proteins and identify prospective pharmacological targets within the context of KSD. This investigation harnessed the unparalleled breadth of plasma protein and KSD pooled genome-wide association study (GWAS) data, sourced from the United Kingdom Biobank Pharma Proteomics Project (UKBPPP) and the FinnGen database version R10. Through Mendelian randomization analysis, proteins exhibiting a causal influence on KSD were pinpointed. Subsequent co-localization analyses affirmed the stability of these findings, while enrichment analyses evaluated their potential for pharmacological intervention. Culminating the study, a phenome-wide association study (PheWAS) was executed, encompassing all phenotypes (2408 phenotypes) catalogued in the FinnGen database version R10. Our MR analysis identified a significant association between elevated plasma levels of proteins FKBPL, ITIH3, and SERPINC1 and increased risk of KSD based on genetic predictors. Conversely, proteins CACYBP, DAG1, ITIH1, and SEMA6C showed a protective effect against KSD, documented with statistical significance (PFDR<0.05). Co-localization analysis confirmed these seven proteins share genetic variants with KSD, signaling a shared genetic basis (PPH3 + PPH4 > 0.8). Enrichment analysis revealed key pathways including hyaluronan metabolism, collagen-rich extracellular matrix, and serine-type endopeptidase inhibition. Additionally, our PheWAS connected the associated proteins with 356 distinct diseases (PFDR<0.05), highlighting intricate disease interrelations. In conclusion, our research elucidated a causal nexus between seven plasma proteins and KSD, enriching our grasp of prospective therapeutic targets.


Subject(s)
Genome-Wide Association Study , Mendelian Randomization Analysis , Proteome , Humans , Nephrolithiasis/genetics , Nephrolithiasis/blood , Nephrolithiasis/metabolism , Phenotype , Proteomics
12.
Mol Genet Genomic Med ; 12(9): e70005, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39225318

ABSTRACT

BACKGROUND: Contiguous gene deletion in the short arm of chromosome 4 is linked to various neurodevelopmental disorders. METHODS: In this study, we conducted peripheral blood chromosome G-banding karyotyping and whole-exome sequencing (WES) on a proband presenting with anal atresia, global developmental delay, lymphocytosis, and other multisystem anomalies. Additionally, chromosome G-banding karyotyping was also carried out on the proband's parents and brother. RESULTS: The 7-month-old proband was found to have a 26.738 Mb 4p15.33-p14 deletion as identified by chromosome G-banding karyotyping and WES. CONCLUSION: We identified a patient with proximal 4p deletion syndrome by karyotype and WES analysis, which might explain some of his phenotypes. Our research enhances clinicians' knowledge of this rare condition, and offers valuable genetic counseling to the affected family. Further research is necessary to identify the causative gene or critical region associated with proximal 4p deletion syndrome.


Subject(s)
Abnormalities, Multiple , Chromosome Deletion , Chromosomes, Human, Pair 4 , Humans , Male , Infant , Abnormalities, Multiple/genetics , Abnormalities, Multiple/pathology , Chromosomes, Human, Pair 4/genetics , Phenotype , Chromosome Disorders/genetics , Chromosome Disorders/pathology , Karyotyping , Exome Sequencing
13.
Rev Cardiovasc Med ; 25(8): 294, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39228482

ABSTRACT

Background: The inflammatory response to atherosclerosis is a process that leads to coronary artery disease. Pan-immune-inflammation value (PIV) has emerged as a new and simple biomarker of inflammation. However, studies on the predictive power of PIV for major adverse cardiovascular events (MACE) or the degree of coronary artery stenosis are scarce. We aimed to explore the predictive ability of PIV for MACE and the degree of coronary artery stenosis in patients with ST-segment elevation myocardial infarction (STEMI) after percutaneous coronary intervention (PCI) during hospitalization. Methods: This study included 542 patients who were diagnosed with STEMI and who underwent PCI between 2016 and 2023 and whose PIV and other inflammatory markers were measured. Using univariate and multivariate logistic regression analysis, risk variables for MACE following PCI and severe coronary stenosis during hospitalization were assessed to create receiver operating characteristic (ROC) curves and determine the best thresholds for inflammatory markers. Spearman correlation analysis was used to evaluate the correlation of PIV and other inflammatory markers with the Gensini score (GS). Results: Compared with the systemic inflammatory index (SII), platelet-to-lymphocyte ratio (PLR), and neutrophil-to-lymphocyte ratio (NLR), the PIV may have greater predictive value in terms of the occurrence of MACE and the degree of coronary stenosis after PCI in hospitalized STEMI patients. The correlation between the PIV and GS was strong. Conclusions: PIV was superior to the SII, PLR, and NLR in predicting inpatient prognosis and severe coronary stenosis after PCI for STEMI patients.

14.
Heliyon ; 10(16): e36039, 2024 Aug 30.
Article in English | MEDLINE | ID: mdl-39247298

ABSTRACT

In order to adjust and detect micro-nano periodic structure optical surface accurately and efficiently, the problem of composite scattering between micro-ellipsoidal periodic structure optical surface and pore defects is studied use the multi-resolution time domain (MRTD) approach. A calculation model is established for the intensity distribution of composite scattering, which is modulated by the micro-ellipsoidal periodic structure optical surface and microdefects. Results are in good agreement with those obtained using CST Microwave Studio software and the finite-different time-domain (FDTD) approach, which demonstrates the effectiveness of the calculation model and method. By combining the field distribution of the micro-ellipsoidal periodic structure optical surface containing microdefects with the optical response at different wavelengths, it is necessary to study the influence of various parameters of the micro-ellipsoidal structure and microdefects on the optical system of metamaterials. The effects of the parameters such as roughness, structure of micro-ellipsoidal unit, defect sizes and buried depths on the composite scattering characteristics are analyzed numerically. The results provide technical support for the fields of functional surface design, ultrasensitive detection, scattering peak orientation and frequency selection.

15.
Mitochondrial DNA B Resour ; 9(9): 1185-1189, 2024.
Article in English | MEDLINE | ID: mdl-39247498

ABSTRACT

Dryas octopetala L. var. asiatica (Nakai) Nakai 1918 is a dwarf shrub that mainly grow in alpine and arctic zones of the Northern Hemisphere, representing an endemic variety in Asia. In the present study, the complete chloroplast (cp) genome of D. octopetala var. asiatica was first characterized and used for its phylogenetic analysis. The cp genome span 158,271 bp with an overall GC content of 36.5%. A total of 129 genes were identified, including 84 protein-coding genes (PCGs), 37 tRNA genes, and 8 rRNA genes. In addition, repetitive sequences and microsatellites were detected within this species. Phylogenetic analysis involving 39 cp genomes from Rosaceae family indicated that D. octopetala var. asiatica was sister to the clade of Amygdaloideae. This study contributes fundamental insights into the cp genome of Dryas octopetala var. asiatica, which will have expanded its use in photosynthesis and evolutionary study.

16.
Drug Dev Res ; 85(6): e22260, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39254376

ABSTRACT

In 2023, the U.S. Food and Drug Administration has approved 29 small molecule drugs. These newly approved small molecule drugs possess the distinct scaffolds, thereby exhibiting diverse mechanisms of action and binding modalities. Moreover, the marketed drugs have always been an important source of new drug development and creative inspiration, thereby fostering analogous endeavors in drug discovery that potentially extend to the diverse clinical indications. Therefore, conducting a comprehensive evaluation of drug approval experience and associated information will facilitate the expedited identification of highly potent drug molecules. In this review, we comprehensively summarized the relevant information regarding the clinical applications, mechanisms of action and chemical synthesis of 29 small molecule drugs, with the aim of providing a promising structural basis and design inspiration for pharmaceutical chemists.


Subject(s)
Drug Approval , United States Food and Drug Administration , United States , Humans , Pharmaceutical Preparations/chemical synthesis , Pharmaceutical Preparations/chemistry , Drug Discovery , Small Molecule Libraries/chemical synthesis
17.
Theranostics ; 14(12): 4874-4893, 2024.
Article in English | MEDLINE | ID: mdl-39239508

ABSTRACT

Rationale: Dysregulated T-cell immune response-mediated inflammation plays critical roles in the pathology of diverse liver diseases, but the underlying mechanism of liver immune homeostasis control and the specific therapies for limiting T-cell overactivation remain unclear. Methods: The metabolic changes in concanavalin A (ConA) mice and autoimmune hepatitis (AIH) patients and their associations with liver injury were analyzed. The expression of purine catabolism nucleases (e.g., CD39 and CD73) on liver cells and immune cells was assessed. The effects of MCregs and their extracellular vesicles (EVs) on CD4+ T-cell overactivation and the underlying mechanism were also explored. Results: Our findings revealed significant alterations in purine metabolism in ConA mice and AIH patients, which correlated with liver injury severity and therapeutic response. CD39 and CD73 were markedly upregulated on CD11b+Gr-1+ MCs under liver injury conditions. The naturally expanded CD39+CD73+Gr-1highCD11b+ MCreg subset during early liver injury effectively suppressed CD4+ T-cell hyperactivation and liver injury both in vitro and in vivo. Mechanistically, MCregs released CD73high EVs, which converted extracellular AMP to immunosuppressive metabolites (e.g., adenosine and inosine), activating the cAMP pathway and inhibiting glycolysis and cytokine secretion in activated CD4+ T cells. Conclusions: This study provides insights into the mechanism controlling immune homeostasis during the early liver injury phase and highlights that MCreg or MCreg-EV therapy may be a specific strategy for preventing diverse liver diseases induced by T-cell overactivation.


Subject(s)
Extracellular Vesicles , Hepatitis, Autoimmune , Mice, Inbred C57BL , Purines , Animals , Extracellular Vesicles/metabolism , Extracellular Vesicles/immunology , Mice , Purines/metabolism , Hepatitis, Autoimmune/immunology , Hepatitis, Autoimmune/metabolism , Hepatitis, Autoimmune/pathology , Humans , Apyrase/metabolism , Liver/metabolism , Liver/immunology , Liver/pathology , Myeloid Cells/metabolism , Myeloid Cells/immunology , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/metabolism , Male , 5'-Nucleotidase/metabolism , Lymphocyte Activation/immunology , Concanavalin A , Female , Disease Models, Animal , Inflammation/metabolism , Inflammation/immunology , Antigens, CD
18.
Int J Med Sci ; 21(11): 2170-2188, 2024.
Article in English | MEDLINE | ID: mdl-39239548

ABSTRACT

Purpose: Matrix metalloproteinase-11 (MMP11), which belongs to the stromelysin subgroup, has been reported to play a role in the progression of colorectal cancer (CRC). However, the significance of MMP11 in the tumor microenvironment, immune/stromal cells, and its mechanism in CRC remain unclear. Methods: The impact of MMP11 knockdown using specific short hairpin RNAs (shRNAs) on the metastasis and invasion of colorectal cancer RKO and SW480 cells was investigated using western blot, quantitative real-time polymerase chain reaction (qRT-PCR), transwell assays, and immunohistochemistry. Results: MMP11 mRNA expression was significantly higher in CRC cells than in normal cells, and its expression was stimulated in CCD-18Co fibroblasts. Additionally, MMP11 expression was found to be higher in individuals aged ≤ 65 years, the T4/T3 group, and Stage III/IV patients. Overall survival (OS) and disease-free survival rates were significantly different between the high and low MMP11 groups. Furthermore, the receiver operating characteristic (ROC) curves for MMP11 at 1-, 3-, and 5-years were 0.450, 0.552, and 0.560, respectively. Moreover, MMP11 promoted the migration and invasion of CRC cells by elevating the expression of Slug protein. Most importantly, MMP11 was positively associated with M0-macrophages and negatively associated with M1-macrophages, NK cells activated, NK cells resting, T cells CD4 memory activated, and T cells follicular helper, indicating the remarkable interactions of MMP11 with tumor immunology. Conclusions: MMP11 plays an important role in colorectal cancer development, and its mechanism in CRC needs to be further explored in the future.


Subject(s)
Cell Movement , Colorectal Neoplasms , Gene Expression Regulation, Neoplastic , Matrix Metalloproteinase 11 , Neoplasm Invasiveness , Snail Family Transcription Factors , Humans , Colorectal Neoplasms/pathology , Colorectal Neoplasms/genetics , Colorectal Neoplasms/mortality , Snail Family Transcription Factors/metabolism , Snail Family Transcription Factors/genetics , Matrix Metalloproteinase 11/genetics , Matrix Metalloproteinase 11/metabolism , Neoplasm Invasiveness/genetics , Cell Movement/genetics , Male , Cell Line, Tumor , Female , Middle Aged , Aged , Tumor Microenvironment/immunology , Tumor Microenvironment/genetics , Disease-Free Survival
19.
Compr Rev Food Sci Food Saf ; 23(5): e13430, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39217522

ABSTRACT

Pulsed vacuum drying (PVD) is a novel vacuum drying method that has demonstrated significant potential in improving energy efficiency and product quality in the drying of foods and agricultural products. The current work provides a comprehensive analysis of the latest advancements in PVD technology, including its historical development, fundamental principles, and mechanistic aspects. The impact of periodic pulsed pressure changes between vacuum and atmospheric pressure on heat and moisture transfer, as well as structural changes in foods at micro- and macro-scales, is thoroughly discussed. The article also highlights the influential drying parameters, the integration of novel auxiliary heaters, and the applications of PVD across various fruits, vegetables, and herbs. Furthermore, the review examines the current status and needs for mathematical modeling of PVD processes, identifying key challenges, research opportunities, and future trends for industrial application. The findings suggest that PVD not only enhances drying efficiency and reduces energy consumption but also preserves the nutritional value, color, and texture of dried products better than traditional methods. Future research should focus on optimizing process parameters and integrating advanced control systems to further improve the scalability and applicability of PVD technology in the food industry.


Subject(s)
Desiccation , Fruit , Vegetables , Vegetables/chemistry , Vacuum , Fruit/chemistry , Desiccation/methods , Food Preservation/methods , Food Handling/methods
20.
Ying Yong Sheng Tai Xue Bao ; 35(6): 1573-1582, 2024 Jun.
Article in Chinese | MEDLINE | ID: mdl-39235015

ABSTRACT

Low temperature (LT) in spring usually occurs at the booting of winter wheat, resulting in reduction of wheat yield. In this study, we used the LT-sensitive wheat cultivar 'Wanmai 52' and the LT-insensitive wheat cultivar 'Yannong 19' as experimental materials to conduct LT treatment (-2 ℃ and 0 ℃) at booting stage. After the LT treatment, we sprayed 6-benzylaminoadenine (6-BA) solutions with concentrations of 10, 20, and 30 mg·L-1 respectively, with equal mass distilled water as control to investigate the effects of spraying 6-BA on the physiological characteristics, yield and quality of wheat flag leaves after LT stress at booting stage. The results showed that compared with the control, young ear of wheat treated with exogenous spraying 6-BA was fuller, the floret morphology was improved, and the number of vascular bundles under the spike was increased. 6-BA application promoted the accumulation of soluble sugar, soluble protein, and proline in flag leaves. The activities of peroxidase and superoxide dismutase were increased, and the content of malondialdehyde was decreased. Exogenous 6-BA application decreased the number of degenerated spikes of wheat, increased the number of grains per spike and 1000-grain weight, as well as the contents of grain protein, wet gluten, and sedimentation value. In summary, exogenous 6-BA application could effectively alleviate the effects of LT stress on flag leaf and yield of wheat. Under the conditions of this experiment, the mitigation effect of spraying 6-BA solution on Yannong 19 was higher than that of Wanmai 52, and the mitigation effect of spraying 20 mg·L-1 6-BA solution on low temperature stress was the best.


Subject(s)
Cold Temperature , Plant Leaves , Purines , Stress, Physiological , Triticum , Triticum/growth & development , Triticum/metabolism , Triticum/drug effects , Triticum/physiology , Plant Leaves/drug effects , Plant Leaves/chemistry , Plant Leaves/metabolism , Purines/pharmacology , Biomass , Plant Growth Regulators/pharmacology , Quality Control , Benzyl Compounds
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