Your browser doesn't support javascript.
loading
: 20 | 50 | 100
1 - 20 de 84
1.
Int Immunopharmacol ; 133: 112025, 2024 May 30.
Article En | MEDLINE | ID: mdl-38677093

Angelica sinensis is a perennial herb widely distributed around the world, and angelica polysaccharide (APS) is a polysaccharide extracted from Angelica sinensis. APS is one of the main active components of Angelica sinensis. A large number of studies have shown that APS has hematopoietic, promoting blood circulation, radiation resistance, lowering blood glucose, enhancing the body immunity and other pharmacological effects in a variety of diseases. However, different extraction methods and extraction sites greatly affect the efficacy of APS. In recent years, with the emerging of new technologies, there are more and more studies on the combined application and structural modification of APS. In order to promote the comprehensive development and in-depth application of APS, this narrative review systematically summarizes the effects of different drying methods and extraction sites on the biological activity of APS, and the application of APS in the treatment of diseases, hoping to provide a scientific basis for the experimental study and clinical application of APS.


Angelica sinensis , Polysaccharides , Humans , Polysaccharides/pharmacology , Polysaccharides/chemistry , Polysaccharides/therapeutic use , Animals , Angelica sinensis/chemistry , Angelica/chemistry , Plant Extracts/pharmacology , Plant Extracts/chemistry , Plant Extracts/therapeutic use
2.
Sci Total Environ ; 919: 170897, 2024 Apr 01.
Article En | MEDLINE | ID: mdl-38346659

The potential increases in carbon stocks in arid regions due to recent shrub encroachment have attracted extensive interest among both ecologists and carbon policy analysts. Quantifying the shrub root biomass amount in these ecosystems is essential to understanding the ecological changes occurring. In this paper, we proposed a simple nondestructive method for estimating the coarse lateral root biomass of shrubs based on the root counts obtained from ground-penetrating radar (GPR) radargrams. Root data were gathered via field experiments using GPR with antenna center frequencies of 900 MHz and 400 MHz. Five Caragana microphylla Lam. shrubs of different sizes were selected for measuring objects, and a total of 40 GPR survey lines were established for GPR data acquisition. The soil profile wall excavation method was used to obtain the total root biomass from each radargram. A model for estimating the root biomass was built by establishing the relationship between the root biomass in each profile and the root counts interpreted from the radargrams. According to the mathematical relationship between the root diameter and root biomass, the proxy root radius was derived, which could explain the rationality of the proposed model from the biological mechanism. The established model provided high confidence in estimating the root dry biomass using the GPR data obtained at the two antenna frequencies (R2= 0.73 for 900 MHz and R2= 0.71 for 400 MHz). The leave-one-out cross-validation results showed that the model exhibits satisfactory performance. This study expands the application of geophysical methods in root research and offers a new simplified method for estimating the root biomass from GPR data under field conditions.


Caragana , Ecosystem , Biomass , Radar , China , Carbon
3.
Brain Res Bull ; 209: 110910, 2024 Apr.
Article En | MEDLINE | ID: mdl-38423190

Ischemic stroke is one of the leading causes of death and disability globally, but its treatment options are limited due to therapeutic window and reperfusion injury constraints. Microglia, astrocytes, and oligodendrocytes are the major components of the neurovascular unit, and there is substantial evidence suggesting their contributions to maintaining homeostasis in the central nervous system. Neuroglial cells participate in neuronal physiological functions and the repair of damaged neurons through various communication methods, including gap junctions, chemical signaling, and extracellular vesicles, in conjunction with other components of the neurovascular unit. Ischemia-induced microglia and astrocytes polarize into "M1/M2" and "A1/A2" phenotypes and exert neurotoxic or neuroprotective effects by releasing soluble factors, secreting extracellular vesicles, and forming syncytia networks in the acute (<72 h), subacute (>72 h), and chronic phases (>6 weeks). Apoptosis of oligodendrocytes due to ischemic hypoxia leads to white matter injury, causing long-term cognitive dysfunction, and promoting oligodendrogenesis is a crucial direction for achieving functional recovery in ischemic stroke. In this article, we summarize the cellular interactions following cerebral ischemia, analyze the roles of neuroglial cells through gap junctions, chemical signaling, and extracellular vesicles in different stages of ischemic stroke, and further explore strategies for intervening in ischemic stroke.


Brain Ischemia , Ischemic Stroke , Stroke , Humans , Neuroglia , Microglia , Neurons , Stroke/drug therapy
4.
J Food Prot ; 87(4): 100244, 2024 Apr.
Article En | MEDLINE | ID: mdl-38378071

Strawberries rapidly deteriorate postharvest, necessitating effective measures to extend their shelf life. This study focused on developing an eco-friendly chitosan-based protective film for strawberry preservation. Strawberries were treated with a coating solution containing varying concentrations of hawthorn leaf extract (HLE) (0.4%, 0.7%, and 1.0%), 1.5% chitosan (CH), and 1% acetic acid. The results demonstrated that coating strawberry fruit with 1% CH-HLE notably delayed fruit spoilage. In-depth analysis revealed that, compared with the uncoated strawberry fruits, the 1% CH-HLE coating effectively reduced weight loss, the respiration intensity, malondialdehyde (MDA) levels, and superoxide anion (O2·-) production. Additionally, the coated strawberries exhibited improved firmness, total soluble solids (TSS), vitamin C (Vc) content, titratable acidity (TA), and total phenolic compound (TPC) content. The enzyme activities of superoxide dismutase (SOD) and catalase (CAT) in the CH-HLE-coated strawberries were greater than those in their uncoated counterparts. The application of a 1% CH-HLE coating successfully delayed spoilage and extend the shelf life of the strawberries by approximately 4-5 days. These findings suggest that CH-HLE has significant potential as a resource for protecting fruits and vegetables, offering an environmentally sustainable solution for postharvest preservation.


Chitosan , Crataegus , Fragaria , Food Preservation/methods , Chitosan/pharmacology , Fruit , Plant Extracts/pharmacology
5.
Int J Pharm ; 654: 123955, 2024 Apr 10.
Article En | MEDLINE | ID: mdl-38423155

Many chemotherapeutic agents can induce immunogenic cell death (ICD), which leads to the release of danger-associated molecular patterns (DAMPs) and tumor-associated antigens. This process promotes dendritic cells (DCs) maturation and cytotoxic T lymphocyte (CTL) infiltration. However, cancer cells can employ diverse mechanisms to evade the host immune system. Recent studies have shown that stimulator of interferon genes (STING) agonists, such as cGAMP, can amplify ICD-triggered immune responses and enhance the infiltration of immune cells into the tumor microenvironment (TME). Building upon these findings, we constructed a doxorubicin (DOX) and cGAMP co-delivery system (DOX/cGAMP@NPs) for melanoma and triple-negative breast cancer (TNBC) therapy. The results demonstrated that DOX could effectively destroy tumors and induce the release of DAMPs by ICD. Furthermore, in orthotopic 4T1 tumors mice model and subcutaneous B16 tumor mice model, cGAMP could promote the maturation of DCs and CD8+ T cell activation and infiltration by inducing the secretion of type I interferons and pro-inflammation cytokine, which amplified the antitumor immune response induced by DOX. This strategy also promoted the depletion of immunosuppressive cells, potentially alleviating the immunosuppressive TME. In conclusion, our study highlights the combination of DOX-induced ICD and the immune-enhancing properties of cGAMP holds significant implications for future research and clinical applications.


Melanoma , Neoplasms , Animals , Mice , Doxorubicin , Nucleotides, Cyclic/pharmacology , Neoplasms/drug therapy , Cytokines , Melanoma/drug therapy , Tumor Microenvironment , Immunotherapy , Cell Line, Tumor
6.
Glob Chang Biol ; 30(1): e17005, 2024 Jan.
Article En | MEDLINE | ID: mdl-37905717

Climate change has induced substantial shifts in vegetation boundaries such as alpine treelines and shrublines, with widespread ecological and climatic influences. However, spatial and temporal changes in the upper elevational limit of alpine grasslands ("alpine grasslines") are still poorly understood due to lack of field observations and remote sensing estimates. In this study, taking the Tibetan Plateau as an example, we propose a novel method for automatically identifying alpine grasslines from multi-source remote sensing data and determining their positions at 30-m spatial resolution. We first identified 2895 mountains potentially having alpine grasslines. On each mountain, we identified a narrow area around the upper elevational limit of alpine grasslands where the alpine grassline was potentially located. Then, we used linear discriminant analysis to adaptively generate from Landsat reflectance features a synthetic feature that maximized the difference between vegetated and unvegetated pixels in each of these areas. After that, we designed a graph-cut algorithm to integrate the advantages of the Otsu and Canny approaches, which was used to determine the precise position of the alpine grassline from the synthetic feature image. Validation against alpine grasslines visually interpreted from a large number of high-spatial-resolution images showed a high level of accuracy (R2 , .99 and .98; mean absolute error, 22.6 and 36.2 m, vs. drone and PlanetScope images, respectively). Across the Tibetan Plateau, the alpine grassline elevation ranged from 4038 to 5380 m (5th-95th percentile), lower in the northeast and southeast and higher in the southwest. This study provides a method for remotely sensing alpine grasslines for the first-time at large scale and lays a foundation for investigating their responses to climate change.


Climate Change , Remote Sensing Technology , Tibet , Grassland , Ecosystem
7.
Chem Biol Interact ; 382: 110623, 2023 Sep 01.
Article En | MEDLINE | ID: mdl-37451665

Triazole scaffolds, a series of 5-membered heterocycles, are well known for their high efficacy, low toxicity, and superior pharmacokinetics. Alzheimer's disease (AD) is the first neurodegenerative disorder with complex pathological mechanisms. Triazole, as an aromatic group with three nitrogen atoms, forms polar and non-polar interactions with diverse key residues in the receptor-ligand binding procedure, and has been widely used in the molecular design in the development of anti-AD agents. Moreover, considering the simple synthesis approaches, triazole scaffolds are commonly used to link two pharmacodynamic groups in one chemical molecule, forming multi-target directed ligands (MTDLs). Furthermore, the click reaction between azide- and cyano-modified enzyme and ligand provides feasibility for the new modulator discovery, compound tissue distribution evaluation, enzyme localization, and pharmacological mechanism study, promoting the diagnosis of AD course.


Alzheimer Disease , Humans , Alzheimer Disease/diagnosis , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Ligands , Triazoles/therapeutic use , Protein Binding , Cholinesterase Inhibitors/chemistry
8.
J Biochem Mol Toxicol ; 37(10): e23436, 2023 Oct.
Article En | MEDLINE | ID: mdl-37376914

Matrine, an effective component extracted from the traditional Chinese herb, Sophora flavescens, has been indicated to exert antitumor activity in different types of cancer. However, the role and precise mechanism of matrine in the progression of liver cancer remains largely unclear. Cell viability, cell proliferation, cell apoptosis, and Warburg effect were estimated by cell counting kit-8 assay, colony formation assay, flow cytometry assay, and glucose uptake and lactate production assay, respectively. The candidate Circular RNAs (circRNAs) were screened by integrating the Gene Expression Omnibus database (GSE155949) analysis with the online program GEO2R. A quantitative real-time polymerase chain reaction was employed to test the expression of circRNA circROBO1, microRNA miR-130a-5p, and roundabout homolog 1 (ROBO1). The interaction of circROBO1/miR-130a-5p/ROBO1 axis was predicted and confirmed by bioinformatics analysis, a dual-luciferase reporter assay, and an RNA pull-down assay. A xenograft mouse model was employed to reveal the role of matrine in vivo. Matrine repressed liver cancer cell viability, proliferation, and Warburg effect, but increased cell apoptosis in vitro. CircROBO1 and ROBO1 were upregulated, but miR-130a-5p was downregulated in liver cancer tissues. Additionally, matrine could reduce the expression of circROBO1 and ROBO1, and increase the expression of miR-130a-5p. Mechanically, overexpression of circROBO1 partly recovered the effect of matrine on liver cancer cell viability, proliferation, apoptosis, and Warburg effect by regulating the miR-130a-5p/ROBO1 axis. Matrine impeded liver cancer development by mediating the circROBO1/miR-130a-5p/ROBO1 axis, which provided a theoretical basis for the application of matrine as an effective anticancer drug for liver cancer.

9.
Leukemia ; 37(6): 1361-1374, 2023 06.
Article En | MEDLINE | ID: mdl-37095209

Hematopoietic stem cells (HSCs) reside at the top of the hematopoietic hierarchy, exhibiting a unique capacity to self-renew and differentiate into all blood cells throughout the lifetime. However, how to prevent HSC exhaustion during long-term hematopoietic output is not fully understood. Here, we show that the homeobox transcription factor Nkx2-3 is required for HSC self-renewal by preserving metabolic fitness. We found that Nkx2-3 is preferentially expressed in HSCs with excessive regenerative potential. Mice with conditional deletion of Nkx2-3 displayed a reduced HSC pool and long-term repopulating capacity as well as increased sensitivity to irradiation and 5-flurouracil treatment due to impaired HSC quiescence. In contrast, overexpression of Nkx2-3 improved HSC function both in vitro and in vivo. Furthermore, mechanistic studies revealed that Nkx2-3 can directly control the transcription of the critical mitophagy regulator ULK1, which is essential for sustaining metabolic homeostasis in HSCs by clearing activated mitochondria. More importantly, a similar regulatory role of NKX2-3 was observed in human cord blood-derived HSCs. In conclusion, our data demonstrate an important role of the Nkx2-3/ULK1/mitophagy axis in regulating the self-renewal of HSCs, therefore providing a promising strategy to improve the function of HSCs in the clinic.


Hematopoietic Stem Cells , Mitophagy , Animals , Humans , Mice , Hematopoietic Stem Cells/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism
10.
Int J Nanomedicine ; 18: 1381-1397, 2023.
Article En | MEDLINE | ID: mdl-36987427

Background: Triple negative breast cancer (TNBC) is one of the most aggressive tumors with high metastasis and mortality, which constitutes 15~20% of all breast cancers. Chemotherapy remains main therapeutic option in the treatment of patients with TNBC. Methods: We developed reactive oxygen species (ROS)-responsive galactosylated nanoparticles (DOX@NPs) as an efficiently targeted carrier for doxorubicin (DOX) delivery to inhibit the growth of TNBC in vitro and in vivo. DOX@NPs were composed of polyacrylate galactose and phenylboronic derivatives conjugation. The in vitro cytotoxicity, cellular uptake, cell apoptosis and cycle distribution of tumor cells treated with different formulations were investigated. Meanwhile in vivo biodistribution and antitumor effects were investigated in a 4T1 tumor-bearing mouse model. Results: DOX@NPs showed good ROS responsiveness and rapid DOX release in the presence of H2O2. Furthermore, our data suggested that DOX@NPs could effectively trigger tumor cells apoptosis and cycle arrest, efficiently accumulate into tumor sites, and suppress tumor growth without adverse side effects. Conclusion: Our results suggested DOX@NP with potent potential as a promising nanocarrier for TNBC therapy, which deserved further investigation for other cancer treatment.


Nanoparticles , Triple Negative Breast Neoplasms , Humans , Animals , Mice , Triple Negative Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/pathology , Reactive Oxygen Species/metabolism , Tissue Distribution , Hydrogen Peroxide , Cell Line, Tumor , Doxorubicin
11.
Mar Drugs ; 21(3)2023 Feb 25.
Article En | MEDLINE | ID: mdl-36976201

Cancer-derived small extracellular vesicles (sEVs) serve as critical mediators of cell-to-cell communication. Manzamine A (MA), a unique marine-derived alkaloid with various bioactivities, exerts anticancer effects against several kinds of tumors, but it remains unclear whether it has the same activity against breast cancer. Here, we proved that MA inhibits MDA-MB-231 and MCF-7 cell proliferation, migration, and invasion in a time- and dose-dependent manner. In addition, MA promotes autophagosome formation but suppresses autophagosome degradation in breast cancer cells. Importantly, we also found that MA stimulates sEVs secretion and increases autophagy-related protein accumulation in secreted sEVs, further potentiated by autophagy inhibitor chloroquine (CQ). Mechanistically, MA decreases the expression level of RIP1, the key upstream regulator of the autophagic pathway, and reduces the acidity of lysosome. Overexpression of RIP1 activated AKT/mTOR signaling, thus attenuating MA-induced autophagy and the corresponding secretion of autophagy-associated sEVs. Collectively, these data suggested that MA is a potential inhibitor of autophagy by preventing autophagosome turnover, and RIP1 mediates MA-induced secretory autophagy, which may be efficacious for breast cancer treatment.


Breast Neoplasms , Humans , Female , Breast Neoplasms/pathology , Autophagy , Signal Transduction , Cell Line, Tumor , Cell Proliferation , Apoptosis
12.
Sci Data ; 9(1): 424, 2022 07 20.
Article En | MEDLINE | ID: mdl-35858958

Remote sensing of nighttime light can observe the artificial lights at night on the planet's surface. The Defense Meteorological Satellite Program's Operational Line Scan (DMSP-OLS) data (1992-2013) provide planet-scale nighttime light data over a long-time span and have been widely used in areas such as urbanization monitoring, socio-economic parameters estimation, and disaster assessment. However, due to the lack of an on-board calibration system, sensor design defects, limited light detection range, and inadequate quantization levels, the applications of DMSP-OLS data are greatly limited by interannual inconsistency, saturation, and blooming problems. To address these issues, we used the power function model based on pseudo-invariant feature, the saturation correction method based on regression model and radiance-calibrated data (SARMRC), and the self-adjusting model (SEAM) to improve the quality of DMSP data, and generated a Consistent and Corrected Nighttime Light dataset (CCNL 1992-2013). CCNL dataset shows good performance in interannual consistency, spatial details of urban centers, and light blooming, which is helpful to fully explore the application potentials of long time series nighttime light data.

13.
Comput Math Methods Med ; 2022: 4593637, 2022.
Article En | MEDLINE | ID: mdl-35903438

Objective: To explore the effect of dydrogesterone tablets combined with Zishen Yutai pills on threatened abortion in early pregnancy and pregnancy outcomes. Methods: This study retrospectively analyzed the clinical data of 100 patients with threatened abortion in early pregnancy who came to the Linhai Second People's Hospital/Taizhou Municipal Hospital from January 13, 2021, to January 13, 2022. According to different treatment methods, 48 patients treated with progesterone injection were assigned to the control group (CG), while 52 cases with the combined therapy of dydrogesterone tablets and Zishen Yutai pills were assigned to the observation group (OG). The two groups were compared in terms of the following parameters: treatment efficacy, whole blood high shear viscosity, hematocrit (HCT), plasma fibrinogen (FIB) level, spiral artery pulsatility index (PI), uterine spiral artery blood flow resistance index (RI), lumbar and abdominal pain relief time, hemostasis time, estrogen levels, pregnancy outcomes, neonatal adverse outcomes, and incidence of adverse reactions. Results: Compared with CG, the therapeutic effect in OG was observed to be evidently better, and its pain relief time and hemostasis time in the waist and abdomen were markedly shorter. After treatment, the whole blood high shear viscosity, FIB, RI, PI, and estrogen levels of both groups improved statistically compared with those before treatment, with more significant improvements in OG compared with CG. OG was also superior to CG with markedly lower incidence of preterm birth, miscarriage, neonatal adverse outcomes, and adverse reactions and a drastically higher full-term pregnancy rate. Conclusion: Zishen Yutai pill combined with dydrogesterone tablets is of remarkable therapeutic effect in treatment of early threatened abortion, which can significantly improve clinical symptoms and pregnancy outcomes of patients, with a high safety profile, which is worthy of clinical application.


Abortion, Threatened , Premature Birth , Abortion, Threatened/drug therapy , Drugs, Chinese Herbal , Dydrogesterone/pharmacology , Dydrogesterone/therapeutic use , Estrogens , Female , Humans , Infant, Newborn , Pregnancy , Pregnancy Outcome , Premature Birth/drug therapy , Retrospective Studies , Tablets/therapeutic use
14.
Exp Ther Med ; 24(1): 485, 2022 Jul.
Article En | MEDLINE | ID: mdl-35761806

Mitochondrial dysregulation is an important pathology that leads to endothelial dysfunction, and the occurrence and development of cardiovascular diseases. Salvianolic acid A (SAA) has been demonstrated to be effective in the treatment of vascular complications of type 2 diabetes mellitus. Limited information has been reported on the effects of SAA on mitochondrial function in endothelial cells. In the present study, the effects of SAA on mitochondrial biogenesis and the related underlying mechanisms were investigated in human umbilical vein endothelial cells (HUVECs). Mitotracker red staining and transmission electron microscopy were used to evaluate the effect of SAA on mitochondrial quality. The effect of SAA treatment on mitochondrial DNA/nuclear DNA ratio of HUVECs was detected by real-time quantitative PCR. Western blot was used to determine the protein expression levels of complex III and Complex IV of mitochondrial oxidative phosphorylation subunit, and ATP production was determined by ATP test kit. Real-time quantitative PCR and Western blot were used to determine the effects of SAA on the expression of peroxisome proliferator-activated receptor γ coactivator (PGC-1α) and its target genes nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (TFAM) proteins and genes. Finally, in the presence of 5'AMP-activated protein kinase (AMPK) specific inhibitors, the expression of PGC-1α, NRF1 and TFAM proteins and the phosphorylation levels of AMPK and Acetyl CoA Carboxylase (ACC) were detected by Western blot or real-time quantitative PCR. The results showed that SAA treatment significantly promoted mitochondrial biogenesis and enhanced mitochondrial function of HUVECs. SAA significantly increased the expression levels of PGC-1α and its target genes NRF1 and (TFAM), a key regulator of mitochondrial biogenesis in HUVECs. These enhancements were accompanied by significantly increased phosphorylation of AMPK and ACC, and were significantly inhibited by specific AMPK inhibitors. These results suggest that SAA may promote mitochondrial biogenesis in endothelial cells by activating the AMPK-mediated PGC-1α/TFAM signaling pathway. These data provide new insights into the mechanism of action of SAA in treating diabetic vascular complications.

15.
Drug Deliv ; 29(1): 970-985, 2022 Dec.
Article En | MEDLINE | ID: mdl-35343862

Lung cancer is the leading cause of cancer death world-wide and its treatment remains a challenge in clinic, especially for non-small cell lung cancer (NSCLC). Thus, more effective therapeutic strategies are required for NSCLC treatment. Quercetin (Que) as a natural flavonoid compound has gained increasing interests due to its anticancer activity. However, poor water solubility, low bioavailability, short half-life, and weak tumor accumulation hinder in vivo applications and antitumor effects of Que. In this study, we developed Que-loaded mixed micelles (Que-MMICs) assembled from 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-poly(ethylene glycol)-biotin (DSPE-PEG-biotin) and poly(ethylene glycol) methyl ether methacrylate-poly[2-(dimethylamino) ethyl acrylate]-polycaprolactone (PEGMA-PDMAEA-PCL) for NSCLC treatment. The results showed that Que was efficiently encapsulated into the mixed micelles and the encapsulation efficiency (EE) was up to 85.7%. Cellular uptake results showed that biotin conjugation significantly improved 1.2-fold internalization of the carrier compared to that of non-targeted mixed micelles. In vitro results demonstrated that Que-MMICs could improve cytotoxicity (IC50 = 7.83 µg/mL) than Que-MICs (16.15 µg/mL) and free Que (44.22 µg/mL) to A549 cells, which efficiently induced apoptosis and arrested cell cycle. Furthermore, Que-MMICs showed satisfactory tumor targeting capability and antitumor efficacy possibly due to the combination of enhanced permeability and retention (EPR) and active targeting effect. Collectively, Que-MMICs demonstrated high accumulation at tumor site and exhibited superior anticancer activity in NSCLC bearing mice model.


Antineoplastic Agents , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Animals , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Mice , Micelles , Quercetin/pharmacology , Quercetin/therapeutic use
16.
Int J Pharm ; 611: 121323, 2022 Jan 05.
Article En | MEDLINE | ID: mdl-34848363

Due to the superior safety and therapeutic efficacy, clopidogrel (CLP) has been widely used to prevent postoperative thrombosis. However, limitations of delayed absorption and metabolic activation of clopidogrel after oral administration hinder its clinic use for acute thrombosis treatment in percutaneous coronary intervention (PCI). Although clopidogrel aqueous injection systems were designed and developed, chemical instability under physiological condition or vascular irritation remains to be solved. In this study, we aim to prepare an injectable clopidogrel loaded submicron emulsion to overcome the drawbacks of conventional clopidogrel aqueous formulation and improve the antiplatelet aggregation effects. Results showed that this delivery system exerted inspiring features including uniform particle size, higher drug loading capacity and sustained drug release behavior. It can dramatically upgrade the formulation stability and prevent the drug degradation under sterilization or higher pH environments. No remarkable droplet size increase or drug content decrease was observed during storage. Compared to CLP tablet, the peak drug concentration (Cmax) and area under the curve (AUC) of CLP emulsion increased by 12.01-fold and 4.69-fold, respectively. Most importantly, it exerted excellent in vivo anti-thrombotic effect on numerous designed animal models. Conclusively, submicron emulsion is a promising delivery system for improving clopidogrel stability and anti-thrombotic efficacy.


Percutaneous Coronary Intervention , Thrombosis , Animals , Clopidogrel , Emulsions , Particle Size , Thrombosis/drug therapy
17.
Cell Mol Biol (Noisy-le-grand) ; 68(8): 110-115, 2022 Aug 31.
Article En | MEDLINE | ID: mdl-36800825

To explore the value of the Helicobacter pylori test in combination with the determination of plasma pepsinogen (PG) and gastrin 17 in screening the precancerous status of gastric cancer and gastric cancer in the healthy population, between 2019 and 2022, we enrolled a total of 402 subjects who went to the physical examination in the Center of Health Management of Ganzhou people's Hospital and additionally underwent the urea (14C) breath test and determination of PGI, PGII and G-17. Anomalies in Hp, PG or G-17 ≥ 2, or a single anomaly in PG determination would be taken as positive, and the diagnosis should be further confirmed by the gastroscopy and pathological test. According to the results, subjects would be further divided into the gastric cancer group, precancerous lesion group, precancerous disease group and control group, aiming to clarify the relationship between Hp, PG and G-17 levels and the precancerous status and development of gastric cancer and the screening value. Results showed that Hp-positive infection was found in 341 subjects (84.82%). Hp infection rate in the control group was much lower than those in the precancerous disease group, precancerous lesion group and gastric cancer group (P < 0.05). The CagA positive rates in the gastric cancer group and precancerous lesion group were significantly higher than those in the precancerous disease group and control group, while the serum level of G-17 in the gastric cancer group was much higher than those in the precancerous lesion group, precancerous disease group and control group (P < 0.05), and the PG I/II ratio in the gastric cancer patients was also lower than those in the precancerous lesion group, precancerous disease group and control group (P < 0.05). As the disease progressed, the G-17 level also increased but PG I/II ratio decreased gradually (P < 0.001). Hp test in combination with PG and G-17 shows a high value in determining the precancerous status of gastric cancer and screening for gastric cancer in healthy subjects.


Helicobacter Infections , Helicobacter pylori , Precancerous Conditions , Stomach Neoplasms , Humans , Stomach Neoplasms/diagnosis , Early Detection of Cancer , Pepsinogen A , Pepsinogen C , Helicobacter Infections/diagnosis , Precancerous Conditions/diagnosis
19.
Cell Mol Biol (Noisy-le-grand) ; 68(9): 160-164, 2022 Sep 30.
Article En | MEDLINE | ID: mdl-36905257

This research aimed to explore the clinical value of thin prep cytologic test (TCT) combined with human papillomavirus (HPV) and carbohydrate antigen 125 (CA125) in early cervical cancer screening in the physical examination population. For this purpose, a total of 3587 females who received gynecological physical examination in the outpatient department of Ganzhou people's Hospital from January 2018 to March 2022 were included and underwent TCT, HPV and carbohydrate antigen 125 upon admission. Colposcopy biopsy was performed on patients who tested positive for any of the three indicators. Then using pathological diagnosis as the gold standard, the three methods applied alone or in combination were evaluated in terms of sensitivity, specificity, diagnostic yield and Youden index. Results showed that Among the 3587 females, 476 (13.27%) were HPV positive, 364 (10.14%) CA125 positive, and 314 (8.75%) TCT positive. Furthermore, 738 tested positive for any of the three indicators and underwent cervical biopsy. Among the 738 cases, 280 (39.94%) developed chronic cervicitis, 268 (36.31%) low-level cervical intraepithelial neoplasia (CIN), 173 (23.44%) high-level CIN, and 17 (2.30%) cervical cancer. HPV+TCT+CA125 combined screening showed higher sensitivity (94.54%), specificity (83.92%), diagnostic coincidence rate (87.46%) and Youden index (0.760) than single-indicator examinations. Also, it had the largest area under the receiver operating characteristic (ROC) curve, 0.673 (0.647, 0.699), compared to any other screening method. In conclusion, The combined detection of CA125, HPV and TCT is of clinical significance due to its higher sensitivity and accuracy in early screening of cervical cancer in the physical examination population.


Papillomavirus Infections , Uterine Cervical Dysplasia , Uterine Cervical Neoplasms , Female , Humans , Early Detection of Cancer/methods , Human Papillomavirus Viruses , Papillomaviridae , Sensitivity and Specificity , Uterine Cervical Dysplasia/diagnosis , Uterine Cervical Neoplasms/pathology
20.
Front Pharmacol ; 12: 653232, 2021.
Article En | MEDLINE | ID: mdl-34220498

Among cancers, colorectal cancer (CRC) has one of the highest annual incidence and death rates. Considering severe adverse reactions associated with classical chemotherapy medications, traditional Chinese medicines have become potential drug candidates. In the current study, the effects of cryptotanshinone (CPT), a major component of Salvia miltiorrhiza Bunge (Danshen) on CRC and underlying mechanism were explored. First of all, data from in vitro experiments and in vivo zebrafish models indicated that CPT selectively inhibited the growth and proliferation of HCT116 and SW620 cells while had little effect on SW480 cells. Secondly, both ER stress and autophagy were associated with CRC viability regulation. Interestingly, ER stress inhibitor and autophagy inhibitor merely alleviated cytotoxic effects on HCT116 cells in response to CPT stimulation, while have little effect on SW620 cells. The significance of apoptosis, autophagy and ER stress were verified by clinical data from CRC patients. In summary, the current study has revealed the anti-cancer effects of CPT in CRC by activating autophagy signaling mediated by ER stress. CPT is a promising drug candidate for CRC treatment.

...