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1.
Nano Lett ; 2024 Sep 06.
Article in English | MEDLINE | ID: mdl-39240781

ABSTRACT

Antiferroelectric materials have shown great potential in electronic devices benefiting from the reversible phase transition between ferroelectric and antiferroelectric phases. Understanding the dipole arrangements and clear phase transition pathways is crucial for design of antiferroelectric materials-based energy storage and conversion devices. However, the specific phase transition details remain largely unclear and even controversial to date. Here, we have grown a series of PbZrO3 on SrTiO3 substrates and elucidated the fine atom structures and phase transition pathways using atomic-resolution transmission electron microscopy. Specifically, a roadmap for ferroelectric to antiferroelectric phase transitions, here with increasing film thickness, is determined as ferroelectric rhombohedral (R3c)-ferroelectric monoclinic (Pc)-ferrielectric orthorhombic (Ima2)-antiferroelectric orthorhombic (Pbam), where Pc and Ima2 phases act as structural bridges. Moreover, the phase transition pathway is strongly related to the synergistic effect of oxygen octahedral tilting and cation displacement. These findings provide an insightful understanding for the theories and related properties of antiferroelectrics.

2.
Colloids Surf B Biointerfaces ; 243: 114135, 2024 Aug 02.
Article in English | MEDLINE | ID: mdl-39106630

ABSTRACT

Myocardial infarction (MI) leads to substantial cellular necrosis as a consequence of reduced blood flow and oxygen deprivation. Stimulating cardiomyocyte proliferation and angiogenesis can promote functional recovery after cardiac events. In this study, we explored a novel therapeutic strategy for MI by synthesizing a biomimetic nanovesicle (NV). This biomimetic NVs are composed of exosomes sourced from umbilical cord mesenchymal stem cells, which have been loaded with placental growth factors (PLGF) and surface-engineered with a cardiac-targeting peptide (CHP) through covalent bonding, termed Exo-P-C NVs. With the help of the myocardial targeting effect of homing peptides, NVs can be enriched in the MI site, thus improve cardiac regeneration, reduce fibrosis, stimulate cardiomyocyte proliferation, and promote angiogenesis, ultimately resulted in improved cardiac functional recovery. It was demonstrated that Exo-P-C NVs have the potential to offer novel therapeutic strategies for the improvement of cardiac function and management of myocardial infarction.

3.
Data Brief ; 55: 110703, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39105063

ABSTRACT

Real-time monitoring of milling parameters is essential to improve machining efficiency and quality, especially for the workpieces with complex geometry. Its main task is to build the relationship between the parameters and the monitoring data. As the relationship is challenging to be established solely through mechanism-driven or data-driven methods, the physics informed method, based on prior physical laws between physical signals and milling parameters, becomes the optimal method. However, this method is limited due to the lack of a high-quality dataset. Therefore, a multi-sensor monitoring dataset for the milling process with various milling parameters and milling materials is built. The variables include cutting depth, cutting width, feed rate, spindle speed and workpiece materials (aluminium alloy 7030 and CK45 steel). The multi-sensor includes force, vibration, noise, and current. A dataset comprising 115 samples is built, including 100 samples collected using the 'all factors' method, and 15 slot milling samples using two different workpiece materials. The 15 slot milling samples are used to calibrate mechanical milling force coefficients, which is beneficial for developing a physics-informed machine learning algorithm.

4.
Zool Res ; 45(5): 1048-1060, 2024 Sep 18.
Article in English | MEDLINE | ID: mdl-39147719

ABSTRACT

Extracellular membrane proteins are crucial for mediating cell attachment, recognition, and signal transduction in the testicular microenvironment, particularly germline stem cells. Cadherin 18 (CDH18), a type II classical cadherin, is primarily expressed in the nervous and reproductive systems. Here, we investigated the expression of CDH18 in neonatal porcine prospermatogonia (ProSGs) and murine spermatogonial stem cells (SSCs). Disruption of CDH18 expression did not adversely affect cell morphology, proliferation, self-renewal, or differentiation in cultured porcine ProSGs, but enhanced cell adhesion and prolonged cell maintenance. Transcriptomic analysis indicated that the down-regulation of CDH18 in ProSGs significantly up-regulated genes and signaling pathways associated with cell adhesion. To further elucidate the function of CDH18 in germ cells, Cdh18 knockout mice were generated, which exhibited normal testicular morphology, histology, and spermatogenesis. Transcriptomic analysis showed increased expression of genes associated with adhesion, consistent with the observations in porcine ProSGs. The interaction of CDH18 with ß-catenin and JAK2 in both porcine ProSGs and murine SSCs suggested an inhibitory effect on the canonical Wnt and JAK-STAT signaling pathways during CDH18 deficiency. Collectively, these findings highlight the crucial role of CDH18 in regulating cell adhesion in porcine ProSGs and mouse SSCs. Understanding this regulatory mechanism provides significant insights into the testicular niche.


Subject(s)
Cadherins , Cell Adhesion , Animals , Male , Swine , Cell Adhesion/physiology , Mice , Cadherins/metabolism , Cadherins/genetics , Mice, Knockout , Spermatogonia/metabolism , Spermatogonia/physiology , Testis/metabolism , Testis/physiology , Adult Germline Stem Cells/metabolism , Adult Germline Stem Cells/physiology , Gene Expression Regulation , Stem Cells/physiology , Stem Cells/metabolism
5.
Food Chem ; 457: 140198, 2024 Nov 01.
Article in English | MEDLINE | ID: mdl-38936127

ABSTRACT

Quercetin (QCT) is a flavonoid with significant health benefits, necessitating sensitive detection methods for food safety and quality control. This study presents a novel UiO-66-TCPP ratiometric fluorescent probe for the quantitative and visual detection of QCT. Under optimal conditions, the fluorescence intensity of UiO-66-TCPP decreased linearly with increasing QCT concentration, with a detection limit of 26 nM. The probe demonstrated high specificity, showing no significant interference from various substances and QCT analogues. Practical applicability was confirmed by testing artificially contaminated juice samples, achieving recovery rates between 98.0% and 104.8%. Furthermore, a paper-based sensor was developed by incorporating UiO-66-TCPP onto Whatman#1 chromatography paper. This sensor exhibited stable fluorescence and a reliable, sensitive visual response to QCT concentrations, detectable via a smartphone-based color recognizer application. The UiO-66-TCPP ratiometric fluorescent probe provides a sensitive, specific, and practical method for detecting QCT in food matrices, offering significant potential for both laboratory and on-site applications.


Subject(s)
Fluorescent Dyes , Food Contamination , Quercetin , Quercetin/analysis , Fluorescent Dyes/chemistry , Food Contamination/analysis , Limit of Detection , Spectrometry, Fluorescence
6.
Int J Lab Hematol ; 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38874282

ABSTRACT

INTRODUCTION: In recent years, the correlation between CD117 antigen and the prognosis of hematological malignancies has been demonstrated. However, there is limited literature on the clinical significance of CD117 antigen in acute promyelocytic leukemia (APL). The aim of this study was to retrospectively analyze the clinical features and prognostic significance of CD117 in APL. METHODS: In this study, we retrospectively investigated the clinicopathological characteristics, outcome, and prognostic impact of negative CD117 expression (CD117-) in 169 APL patients treated with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) containing regimen. RESULTS: The median follow-up period was 63.0 months. CD117- was detected in 13 APL patients (7.7%). No significant differences were found in baseline characteristics between CD117+ and CD117- subgroups. However, compared to CD117+ APL, the incidence of early death (ED) was significantly higher in CD117- APL (p = 0.023). By multivariate analysis, CD117- was an independent adverse prognostic factor for overall survival (OS) and progression-free survival (PFS) (p = 0.022 and p = 0.014, respectively). CONCLUSIONS: To sum up, CD117- is associated with greater risk of ED and has the statistical power to predict inferior OS and PFS, this marker may be considered to build prognostic scores for risk-adapted therapeutic strategies in APL management.

7.
Int J Biol Macromol ; 273(Pt 1): 133043, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38857728

ABSTRACT

Water pollution is one of serious environmental issues due to the rapid development of industrial and agricultural sectors, and clean water resources have been receiving increasing attention. Recently, more and more studies have witnessed significant development of catalysts (metal oxides, metal sulfides, metal-organic frameworks, zero-valent metal, etc.) for wastewater treatment and water purification. Sustainable and clean catalysts immobilized into chitosan-based materials (Cat@CSbMs) are considered one of the most appealing subclasses of functional materials due to their high catalytic activity, high adsorption capacities, non-toxicity and relative stability. This review provides a summary of various upgrading renewable Cat@CSbMs (such as cocatalyst, photocatalyst, and Fenton-like reagent, etc.). As for engineering applications, further researches of Cat@CSbMs should focus on treating complex wastewater containing both heavy metals and organic pollutants, as well as developing continuous flow treatment methods for industrial wastewater using Cat@CSbMs. In conclusion, this review abridges the gap between different approaches for upgrading renewable and clean Cat@CSbMs and their future applications. This will contribute to the development of cleaner and sustainable Cat@CSbMs for wastewater treatment and water purification.


Subject(s)
Chitosan , Wastewater , Water Pollutants, Chemical , Water Purification , Chitosan/chemistry , Water Purification/methods , Catalysis , Wastewater/chemistry , Water Pollutants, Chemical/chemistry , Water Pollutants, Chemical/isolation & purification , Adsorption , Metals, Heavy/chemistry , Metals, Heavy/isolation & purification
8.
J Med Chem ; 67(11): 9645-9661, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38776419

ABSTRACT

While a number of p53-MDM2 inhibitors have progressed into clinical trials for the treatment of cancer, their progression has been hampered by a variety of problems, including acquired drug resistance, dose-dependent toxicity, and limited clinical efficiency. To make more progress, we integrated the advantages of MDM2 inhibitors and platinum drugs to construct novel PtIV-RG7388 (a selective MDM2 inhibitor) complexes. Most complexes, especially 5a and 5b, displayed greatly improved antiproliferative activity against both wild-type and mutated p53 cancer cells. Remarkably, 5a exhibited potent in vivo tumor growth inhibition in the A549 xenograft model (66.5%) without apparent toxicity. It arrested the cell cycle at both the S phase and the G2/M phase and efficiently induced apoptosis via the synergistic effects of RG7388 and cisplatin. Altogether, PtIV-RG7388 complex 5a exhibited excellent in vitro and in vivo antitumor activities, highlighting the therapeutic potential of PtIV-RG7388 complexes as antitumor agents.


Subject(s)
Antineoplastic Agents , Proto-Oncogene Proteins c-mdm2 , Tumor Suppressor Protein p53 , Humans , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/therapeutic use , Proto-Oncogene Proteins c-mdm2/antagonists & inhibitors , Proto-Oncogene Proteins c-mdm2/metabolism , Tumor Suppressor Protein p53/metabolism , Tumor Suppressor Protein p53/antagonists & inhibitors , Animals , Cell Line, Tumor , Mice , Apoptosis/drug effects , Cell Proliferation/drug effects , Organoplatinum Compounds/pharmacology , Organoplatinum Compounds/chemistry , Organoplatinum Compounds/chemical synthesis , Mice, Nude , Xenograft Model Antitumor Assays , Structure-Activity Relationship , Drug Discovery , Mice, Inbred BALB C , Pyrrolidines , para-Aminobenzoates
9.
Nano Lett ; 24(14): 4082-4090, 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38526914

ABSTRACT

The generally nonpolar SrTiO3 has attracted more attention recently because of its possibly induced novel polar states and related paraelectric-ferroelectric phase transitions. By using controlled pulsed laser deposition, high-quality, ultrathin, and strained SrTiO3 layers were obtained. Here, transmission electron microscopy and theoretical simulations have unveiled highly polar states in SrTiO3 films even down to one unit cell at room temperature, which were stabilized in the PbTiO3/SrTiO3/PbTiO3 sandwich structures by in-plane tensile strain and interfacial coupling, as evidenced by large tetragonality (∼1.05), notable polar ion displacement (0.019 nm), and thus ultrahigh spontaneous polarization (up to ∼50 µC/cm2). These values are nearly comparable to those of the strong ferroelectrics as the PbZrxTi1-xO3 family. Our findings provide an effective and practical approach for integrating large strain states into oxide films and inducing polarization in nonpolar materials, which may broaden the functionality of nonpolar oxides and pave the way for the discovery of new electronic materials.

10.
J Org Chem ; 89(3): 1748-1752, 2024 Feb 02.
Article in English | MEDLINE | ID: mdl-38262733

ABSTRACT

A highly enantioselective catalytic reduction of pyrazolo[1,5-a]pyrimidine to zanubrutinib has been realized by the Ir/(R)-t-Bu-FcPhox complex. This chiral product could be obtained in up to >99% ee in the asymmetric transformation without any other additives, providing a new route for the asymmetric synthesis of zanubrutinib.

11.
J Ethnopharmacol ; 324: 117749, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38219880

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Obesity has become a public burden worldwide due to its booming incidence and various complications, and browning of white adipose tissue (WAT) is recognized as a hopeful strategy to combat it. Blossom of Citrus aurantium L. var. amara Engl. (CAVA) is a popular folk medicine and dietary supplement used for relieving dyspepsia, which is recorded in the Chinese Materia Medica. Our previous study showed that blossom of CAVA had anti-obesity potential, while its role in browning of WAT was still unclear. AIM OF THE STUDY: This study aimed to characterize the constituents in flavonoids from blossom of CAVA (CAVAF) and to clarify the anti-obesity capacities especially the effects on browning of WAT. MATERIALS AND METHODS: Gradient ethanol eluents from blossom of CAVA were obtained by AB-8 macroporous resin. 3T3-L1 cells and pancreatic lipase inhibition assay were employed to investigate the potential anti-obesity effects in vitro. HPLC and UPLC/MS assays were performed to characterize the chemical profiles of different eluents. Network pharmacology and molecular docking assays were used to reveal potential anti-obesity targets. Furthermore, high-fat diet (HFD)-induced mice were constructed to explore the anti-obesity actions and mechanisms in vivo. RESULTS: 30% ethanol eluents with high flavonoid content and great inhibition on proliferation of 3T3-L1 preadipocytes and pancreatic lipase activity were regarded as CAVAF. 19 compounds were identified in CAVAF. Network pharmacology analysis demonstrated that AMPK and PPARα were potential targets for CAVAF in alleviating obesity. Animal studies demonstrated that CAVAF intervention significantly decreased the body weight, WAT weight, serum TG, TC and LDL-C levels in HFD-fed obese mice. HFD-induced insulin resistance and morphological changes in WAT and brown adipose tissue were also markedly attenuated by CAVAF treatment. CAVAF supplementation potently inhibited iWAT inflammation by regulating IL-6, IL-1ß, TNF-α and IL-10 mRNA expression in iWAT of mice. Furthermore, the gene expression levels of thermogenic markers including Cyto C, ATP synthesis, Cidea, Cox8b and especially UCP1 in iWAT of mice were significantly up-regulated by CAVAF administration. CAVAF intervention also markedly increased the expression levels of PRDM16, PGC-1α, SIRT1, AMPK-α1, PPARα and PPARγ mRNA in iWAT of mice. CONCLUSION: CAVAF treatment significantly promoted browning of WAT in HFD-fed mice. These results suggested that flavonoid extracts from blossom of CAVA were probably promising candidates for the treatment of obesity.


Subject(s)
Citrus , Flavonoids , Mice , Animals , Flavonoids/pharmacology , Flavonoids/therapeutic use , Diet, High-Fat/adverse effects , AMP-Activated Protein Kinases/metabolism , Molecular Docking Simulation , PPAR alpha , Adipose Tissue, White , Obesity/metabolism , Ethanol/pharmacology , Citrus/chemistry , RNA, Messenger , Lipase , Mice, Inbred C57BL
12.
Sci Total Environ ; 915: 170116, 2024 Mar 10.
Article in English | MEDLINE | ID: mdl-38232831

ABSTRACT

Pyrolysis is an effective method for treating of livestock and poultry manure developed in recent years. It can completely decompose pathogens and antibiotics, stabilize heavy metals, and enrich phosphorus (P) in biochar. To elucidate the P migration mechanism under different pig manure pyrolysis temperatures, sequential fractionation, solution 31P nuclear magnetic resonance, X-ray photoelectron spectroscopy, X-ray diffraction, and K-edge X-ray absorption near-edge structure techniques were used to analyze the P species in pig manure biochar (PMB). The results indicated that most of the organic P in the pig manure was converted to inorganic P during pyrolysis. Moreover, the transformation to different P groups pathways was clarified. The phase transition from amorphous to crystalline calcium phosphate was promoted when the temperature was above 600 °C. The content of P extracted by hydrochloric acid, which was the long-term available P for plant uptake, increased significantly. PMB pyrolyzed at 600 °C can be used as a highly effective substitute for P source. It provides the necessary P species (e.g. water-soluble P.) and metal elements for the growth of water spinach plants, and which are slow-release comparing with the Hogland nutrient solution.


Subject(s)
Manure , Pyrolysis , Animals , Swine , Hydroponics , Phosphorus/chemistry , Charcoal/chemistry
13.
Int J Biol Macromol ; 254(Pt 2): 127887, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37935288

ABSTRACT

A cleaner and safer environment is one of the most important requirements in the future. It has become increasingly urgent and important to fabricate novel environmentally-friendly materials to remove various hazardous pollutants. Compared with traditional materials, chitosan is a more environmentally friendly material due to its abundance, biocompatibility, biodegradability, film-forming ability and hydrophilicity. As an abundant of -NH2 and -OH groups on chitosan molecular chain could chelate with all kinds of metal ions efficiently, chitosan-based materials hold great potential as a versatile supporting matrix for metal oxide nanomaterials (MONMs) (TiO2, ZnO, SnO2, Fe3O4, etc.). Recently, many chitosan/metal oxide nanomaterials (CS/MONMs) have been reported as adsorbents, photocatalysts, heterogeneous Fenton-like agents, and sensors for potential and practical applications in environmental remediation and monitoring. This review analyzed and summarized the recent advances in CS/MONMs composites, which will provide plentiful and meaningful information on the preparation and application of CS/MONMs composites for wastewater treatment and help researchers to better understand the potential of CS/MONMs composites for environmental remediation and monitoring. In addition, the challenges of CS/MONM have been proposed.


Subject(s)
Chitosan , Environmental Pollutants , Environmental Restoration and Remediation , Nanocomposites , Water Pollutants, Chemical , Oxides , Adsorption
14.
Pacing Clin Electrophysiol ; 47(1): 167-171, 2024 01.
Article in English | MEDLINE | ID: mdl-38041413

ABSTRACT

BACKGROUND: Atrial esophageal fistula (AEF) is a lethal complication that can occur post atrial fibrillation (AF) ablation. Esophageal injury (EI) is likely to be the initial lesion leading to AEF. Endoscopic examination is the gold standard for a diagnosis of EI but extensive endoscopic screening is invasive and costly. This study was conducted to determine whether fecal calprotectin (Fcal), a marker of inflammation throughout the intestinal tract, may be associated with the existence of esophageal injury. METHODS: This diagnostic study was conducted in a cohort of 166 patients with symptomatic AF undergoing radiofrequency catheter ablation from May 2020 to June 2021. Fcal tests were performed 1-7 days after ablation. All patients underwent endoscopic ultrasonography 1 or 2 days after ablation. RESULTS: The levels of Fcal were significantly different between the EI and non-EI groups (404.9 µg/g (IQR 129.6-723.6) vs. 40.4 µg/g (IQR 15.0-246.2), p < .001). Analysis of ROC curves revealed that a Fcal level of 125 µg/g might be the optimal cut-off value for a diagnosis of EI, giving a 78.8% sensitivity and a 65.4% specificity. The negative predictive value of Fcal was 100% for ulcerated EI. CONCLUSIONS: The level of Fcal is associated with EI post AF catheter ablation. 125 µg/g might be the optimal cut-off value for a diagnosis of EI. Negative Fcal could predict the absence of ulcerated EI, which could be considered a precursor to AEF.


Subject(s)
Atrial Fibrillation , Catheter Ablation , Esophageal Fistula , Humans , Atrial Fibrillation/diagnosis , Atrial Fibrillation/surgery , Leukocyte L1 Antigen Complex , Heart Atria , Esophageal Fistula/etiology , Catheter Ablation/adverse effects
15.
Plant Dis ; 2023 Oct 25.
Article in English | MEDLINE | ID: mdl-37877995

ABSTRACT

Root-knot nematodes of the genus Meloidogyne parasitize the roots of thousands of plants and can cause severe damage and yield loss. Here, we report a new root-knot nematode, Meloidogyne limonae n. sp., parasitizing "lemon" (Citrus limon) in Hainan Province, South China. Lemon trees infected by the root-knot nematode showed poor-quality lemons, chlorosis of foliage, weak growth, and numerous root galls with white females and egg masses protruding outside. Phylogenetic trees of sequences within the ribosomal and mitochondria DNA demonstrated that this species differs clearly from other previously described root-knot nematodes. Morphologically, the new species is characterized by an oval-shaped perineal pattern and the lateral field marked by a ridge of cuticle on one or both sides, the dorsal arch is low with fine to coarse, smooth cuticle striae, vulva slit centrally located at the unstriated area; spicules of males are arcuate, curved ventrally; gubernaculum is distinct and curved; labial disc of second-stage juveniles is prominent and dumbbell-shaped; stylet knobs oval and sloping backwardly; pharyngeal glands not filling the body cavity, overlapping intestine ventrally; conical tail gradually tapering. Phylogenetic trees based on ITS1-5.8S-ITS2, D2-D3 of the 28S rDNA, and the COI and COII-16S rRNA genes of the mtDNA showed that Meloidogyne limonae n. sp. belongs to an undescribed root-knot nematode lineage that is separated from other species with the resemblance in morphology, such as M. floridensis M. hispanica, M. acronea, and M. paranaenis.

16.
J Ovarian Res ; 16(1): 201, 2023 Oct 13.
Article in English | MEDLINE | ID: mdl-37833722

ABSTRACT

BACKGROUND: The factors affecting the cumulative live birth rate (CLBR) of PCOS (Polycystic ovary syndrom) patients who received in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) needs more research for a better outcome. METHODS: Here we carried out a retrospective analysis of 1380 PCOS patients who received IVF/ICSI-ET for the first time from January 2014 to December 2016. We divided them into cumulative live birth group (group A) and non-cumulative live birth group (group B) according to whether there were live births. RESULTS: The conservative cumulative live birth rate was 63.48%. There were 876 cumulative live births (group A) and 504 non-cumulative live births (group B) according to whether the patients had live births or not. Competition analysis showed that duration of infertility, primary/secondary type of infertility, stimulation protocols, starting dose of gonadotrophins and oocyte retrieved numbers were significantly correlated with CLBR. The Cox proportional risk regression model of PCOS patients showed that stimulation protocols had a significant impact on CLBR. Patients in the GnRH (Gonadotropin-releasing hormone)-antagonist protocol group and the mild stimulation protocol had lower CLBR than those in the prolonged GnRH-agonist protocol, which was statistically significant. PCOS patients with the starting dose of gonadotrophins greater than 112.5u had lower CLBR than those with less than 100u, which was statistically significant. Women with 11-15 oocytes and 16-20 oocytes had higher CLBR than women with 1-9 oocytes, which was statistically significant. CONCLUSIONS: When we used Prolonged GnRH-agonist protocol, or the first starting dose of gonadotrophins was 100u-112.5u, or the number of oocytes obtained was 11-15 and 16-20, the CLBR of PCOS patients increased significantly after the 1st oocyte collection.


Subject(s)
Infertility , Polycystic Ovary Syndrome , Male , Pregnancy , Humans , Female , Sperm Injections, Intracytoplasmic , Birth Rate , Retrospective Studies , Ovulation Induction/methods , Semen , Fertilization in Vitro , Gonadotropins , Gonadotropin-Releasing Hormone , Live Birth , Oocytes , Pregnancy Rate
17.
Cancer Med ; 12(17): 17766-17775, 2023 09.
Article in English | MEDLINE | ID: mdl-37584196

ABSTRACT

BACKGROUND: The innovative combination of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) has established a new chapter of curative approach in acute promyelocytic leukemia (APL). The disease characteristics and prognostic influence of additional cytogenetic abnormalities (ACA) in APL with modern therapeutic strategy need to be elucidated. METHODS: In the present study, we retrospectively investigated disease features and prognostic power of ACA in 171 APL patients treated with ATRA-ATO-containing regimens. RESULTS: Patients with ACA had markedly decreased hemoglobin levels than that without ACA (p = 0.021). Risk stratification in the ACA group was significantly worse than that in the non-ACA group (p = 0.032). With a median follow-up period of 62.0 months, worse event-free survival (EFS) was demonstrated in patients harboring ACA. Multivariate analysis showed that ACA was an independent adverse factor for EFS (p = 0.033). By further subgroup analysis, in CD34 and CD56 negative APL, patients harboring ACA had inferior EFS (p = 0.017; p = 0.037). CONCLUSIONS: To sum up, ACA remains the independent prognostic value for EFS, we should build risk-adapted therapeutic strategies in the long-term management of APL when such abnormalities are detected.


Subject(s)
Arsenicals , Leukemia, Promyelocytic, Acute , Humans , Leukemia, Promyelocytic, Acute/diagnosis , Leukemia, Promyelocytic, Acute/drug therapy , Leukemia, Promyelocytic, Acute/genetics , Progression-Free Survival , Retrospective Studies , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Tretinoin/therapeutic use , Chromosome Aberrations , Oxides/therapeutic use , Arsenicals/therapeutic use , Treatment Outcome
18.
ACS Nano ; 17(14): 13461-13473, 2023 07 25.
Article in English | MEDLINE | ID: mdl-37449998

ABSTRACT

Competitive consumption of nutrients between rapidly proliferating cancer cells and T cells results in an immunosuppressive tumor microenvironment (TME) and nutrient deprivation of T cells, which can cause low response rate and resistance to immunotherapies. In this study, we proposed a dual-mechanism based nutrient partitioning nanoregulator (designated as DMNPN), which can simultaneously regulate the immunosuppressive TME and enhance T cell nutrient availability. DMNPN consists of a charge-reversal biodegradable mesoporous silica, encapsulating glycolysis inhibitor lonidamine, and small interfering RNA against glutaminase. Through inhibiting glycolysis to decrease the lactic acid production and downregulating glutaminase expression to reduce the uptake of glutamine by tumor cells, DMNPN enables effective remodeling of metabolism and nutrient partitioning, which alleviates the immunosuppressive TME and boosts nutrient availability for T cells with enhanced antitumor immunity. Such a nutrient partitioning nanoregulator can effectively inhibit the growth of anti-programmed death receptor 1 (anti-PD-1) resistant tumors and prevent tumor metastasis and recurrence. Overall, this dual-mechanism based nutrient reallocation strategy provides a promising approach for cancer therapy.


Subject(s)
Glutaminase , Neoplasms , Humans , Glutaminase/pharmacology , Neoplasms/therapy , Immunotherapy/methods , T-Lymphocytes , Immunosuppressive Agents/pharmacology , Nutrients , Tumor Microenvironment , Cell Line, Tumor
19.
Mol Med Rep ; 28(2)2023 08.
Article in English | MEDLINE | ID: mdl-37350394

ABSTRACT

Acute myeloid leukemia (AML) is a clonal malignant proliferative disease. In recent years, with the use of all­trans retinoic acid to induce cancer cell differentiation in acute promyelocytic leukemia, and its advantages of high efficacy and low toxic side effects, tumor differentiation therapy has become a research hotspot; however, the mechanisms underlying its role remain to be fully established. Nod­like receptor family pyridine domain containing 3 (NLRP3) is the most extensively studied and well­characterized inflammasome, is involved in a variety of inflammation­related diseases, including cancer, and is a very attractive potential target for the study of novel therapeutic agents. Activation of the NLRP3 inflammasome is a double­edged sword in tumor therapy, with evidence of protective anti­tumor and pro­tumor effects in different types of cancer. Whether the NLRP3 inflammasome promotes disease progression or exerts a protective anti­tumor effect in hematological malignancies remains contested. In the present study, the protective anti­tumor effects of NLRP3 on leukemia cells during their differentiation and maturation were investigated. It was found that the upregulation of NLRP3 expression induced using Phorbol 12­Myristate 13­Acetate played a role in promoting the differentiation and maturation of leukemia cells into monocytes/macrophages, and it was directly involved in the apoptosis of leukemia cells and the differentiation and maturation of CD11b+ cells. These results provide novel theoretical evidence for exploring the mechanism of differentiation therapy in leukemia and improves our understanding of the role of NLRP3 in hematologic tumors.


Subject(s)
Inflammasomes , Leukemia , Humans , Inflammasomes/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Apoptosis , Cell Differentiation
20.
J Med Chem ; 66(12): 8066-8085, 2023 06 22.
Article in English | MEDLINE | ID: mdl-37306362

ABSTRACT

Recently, artemisinin and derivatives have been revealed to possess encouraging antitumor activity. Herein, we integrated the antitumor advantages of artesunate and platinum drugs to construct novel PtIV-artesunate dual-action and triple-action complexes. Most derivatives, especially 10f, displayed broad-spectrum and potent in vitro antitumor activities against a number of cancer cell lines. Compound 10f displayed potent antimetastasis and anticlonogenic activities, efficiently induced autophagic cell death and apoptosis, and arrested the cell cycle at both S and G2/M phases. More importantly, it displayed remarkable in vivo antitumor efficacy in the A549 xenograft model (TGI = 53.4%; 6 µmol/kg) with low toxicity. In addition to the antitumor application, 10f showed potent in vivo antimalarial activity in malarial-infected mice model and obviously alleviated malarial-related multiorgan injury. This conjugation greatly improved safety, especially reducing the platinum drugs' nephrotoxicity. Taken together, this study highlighted the therapeutic potential of PtIV-artesunate complexes as antitumor and antimalarial agents.


Subject(s)
Antimalarials , Antineoplastic Agents , Prodrugs , Mice , Animals , Humans , Platinum/pharmacology , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Antimalarials/pharmacology , Antimalarials/therapeutic use , Artesunate/pharmacology , Artesunate/therapeutic use , Prodrugs/pharmacology , Prodrugs/therapeutic use , Cell Line, Tumor , Apoptosis
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