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1.
Eur J Med Chem ; 280: 116933, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-39368262

ABSTRACT

For clinically prevalent traumatic optic neuropathy (TON) and other retinal and optic nerve injuries lacking effective therapeutic agents, there is an urgent clinical demand for developing highly efficient and safe neuroprotective agents. Here, we have integrated naturally sourced chalcone with isatin through a catalyst-free green synthesis method, reporting a series of spirocyclic chalcone derivatives with significantly lower cytotoxicity than chalcone itself. Following in vitro cell protection assays in models of hydrogen peroxide and glutamic acid-induced damage, multiple active compounds capable of combating both forms of damage were identified. Among these, candidate compound X38 demonstrated promising neuroprotective prospects: in vitro, it attenuated glutamate-induced cell apoptosis, while in vivo, it effectively ameliorated retinal thinning and loss of optic nerve electrophysiological function induced by optic nerve injury. Preliminary mechanistic studies suggest that X38 exerts its neuroprotective effects by mitigating intracellular ROS accumulation, inhibiting JNK phosphorylation, and alleviating oxidative stress. Additionally, acute toxicity studies (intraperitoneal injection, 500 mg/kg) underscored the favorable in vivo safety profile of X38. Taken together, this study has designed a class of safe, neuroprotective spirocyclic chalcone derivatives that can be synthesized using green methods, offering an attractive candidate for treating retinal and optic nerve injuries.

2.
Article in English | MEDLINE | ID: mdl-39366518

ABSTRACT

Cocaine use disorder (CUD) is a chronic and relapsing neuropsychiatric disorder characterized by structural and functional brain lesions, posing a significant public health challenge. While the disruptive effects of cocaine on neurotransmitter systems (receptors/transporters) have been well established, the patterns of brain structural abnormalities in CUD and its interaction with other factors remain an ongoing topic of investigation. We employed source-based morphometry (SBM), a multivariate approach on 50 CUD participants and 50 matched healthy controls from the public SUDMEX CONN dataset. This method allowed us to identify co-varying patterns of brain tissue volume differences, and further explore the effect of average cocaine dosage through moderation analysis. Spatial correlation analysis was also performed to examine micro-macro structural consistency between tissue volume variations and chemoarchitectural distribution of dopamine and serotonin. Our SBM analysis findings were consistent with reward-related neuroadaptations in the striato-thalamo-cortical and limbic pathways and also exhibited co-localization with the distribution of dopamine and serotonin systems. The moderation analysis suggested that the average dosage positively strengthens cocaine consumption years' effect on brain structures. By integrating our findings of gray and white matter volume differences and corresponding neurotransmitter profiles, this comprehensive view not only strengthens our understanding of the brain's structural abnormalities in CUD, but also reveals potential mechanisms underlying its development and progression.

3.
J Phys Chem B ; 2024 Oct 02.
Article in English | MEDLINE | ID: mdl-39356838

ABSTRACT

Task-specific ionic liquids (ILs) employing carbanions represent a new class of ILs for carbon capture. The deprotonated malononitrile carbanion, [CH(CN)2]-, has shown close to equimolar capacity for reactive CO2 capture. Although the formation of the [C(CN)2COOH]- carboxylic acid was found to be the final product, how the hydrogen atom on the [CH(CN)2]- carbanion transfers to the carboxylate group as a proton has not been fully understood. In this work, we employ density functional theory calculations with an implicit solvation model to investigate the proton transfer mechanisms in forming carboxylic acid from the reaction of the [CH(CN)2]- carbanion with CO2. We find that the intramolecular proton-transfer pathway in [CH(CN)2COO]- to form [C(CN)2COOH]- is unlikely due to the high energy barrier of 152 kJ/mol. Instead, the intermolecular proton transfer pathway between two [CH(CN)2COO]- anions is more feasible to form two molecules of [C(CN)2COOH]-, with a significantly lower activation energy of 50 kJ/mol. Moreover, the [C(CN)2COOH]- dimer is further stabilized by the intermolecular hydrogen bonds of the two -COOH groups in the Z-configuration of the π-conjugated planar geometry. This insight of reactive CO2 capture enabled by intermolecular proton transfer will be useful in designing novel carbanions and ILs for carbon capture and conversion.

4.
Int J Pharm ; 665: 124706, 2024 Nov 15.
Article in English | MEDLINE | ID: mdl-39277152

ABSTRACT

TGF-ß is a crucial regulator in tumor microenvironment (TME), especially for myofibroblastic cancer-associated fibroblasts (myCAFs). The myCAFs can be motivated by TGF-ß signaling to erect pro-tumor TME, meanwhile, myCAFs overexpress TGF-ß to mediate the crosstalk between tumor and stromal cells. The blockade of TGF-ß can break cancer-associated fibroblasts barrier, consequently opening the access for drugs into tumor. The TGF-ß is a promising target in anti-tumor therapy. Herein, we introduced a two-stage combination therapy (TC-Therapy), including TGF-ß receptor I inhibitor SB525334 (SB) and cytotoxicity agent docetaxel micelle (DTX-M). We found that SB and DTX-M synergistically inhibited myCAFs proliferation and elevated p53 protein expression in BxPC-3/3T3 mixed cells. Gene and protein tests demonstrated that SB cut off TGF-ß signaling via receptor blockade and it did not arouse TGF-ß legend compensated internal autocrine. On the contrary, two agents combined decreased TGF-ß secretion and inhibited myCAFs viability marked by α-SMA and FAPα. TC-Therapy was applied in BxPc-3/3T3 mixed tumor-bearing mice model. After TC-Therapy, the α-SMA+/ FAPα+ myCAFs faded increasingly and collagenous fibers mainly secreted by myCAFs decreased dramatically as well. More than that, the myCAFs barrier breaking helped to normalize micro-vessels and paved way for micelle penetration. The TGF-ß protein level of TC-Therapy in TME was much lower than that of simplex DTX-M, which might account for TME restoration. In conclusion, TGF-ß inhibitor acted as the pioneer before nano chemotherapeutic agents. The TC-Therapy of TGF-ß signaling inhibition and anti-tumor agent DTX-M is a promising regimen without arising metastasis risk to treat pancreatic cancer. The therapeutic regimen focused on TGF-ß related myCAFs reminds clinicians to have a comprehensive understanding of pancreatic cancer.


Subject(s)
Antineoplastic Agents , Cancer-Associated Fibroblasts , Docetaxel , Micelles , Pancreatic Neoplasms , Transforming Growth Factor beta , Docetaxel/administration & dosage , Docetaxel/pharmacology , Animals , Cancer-Associated Fibroblasts/drug effects , Cancer-Associated Fibroblasts/metabolism , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/pathology , Mice , Transforming Growth Factor beta/antagonists & inhibitors , Transforming Growth Factor beta/metabolism , Cell Line, Tumor , Humans , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/pharmacology , Tumor Microenvironment/drug effects , Cell Proliferation/drug effects , Receptor, Transforming Growth Factor-beta Type I/antagonists & inhibitors , Receptor, Transforming Growth Factor-beta Type I/metabolism , 3T3 Cells , Signal Transduction/drug effects , Mice, Inbred BALB C , Drug Delivery Systems/methods , Imidazoles , Quinoxalines
5.
Biochem Pharmacol ; 230(Pt 1): 116554, 2024 Sep 25.
Article in English | MEDLINE | ID: mdl-39332693

ABSTRACT

The rapidly rising prevalence of metabolic diseases has turned them into an escalating global health concern. By producing or altering metabolic products, the gut microbiota plays a pivotal role in maintaining human health and influencing disease development. These metabolites originate from the host itself or the external environment. In the system of interactions between microbes and the host, tryptophan (Trp) plays a central role in metabolic processes. As the amino acid in the human body that must be obtained through dietary intake, it is crucial for various physiological functions. Trp can be metabolized in the gut into three main products: The gut microbiota regulates the transformation of 5-hydroxytryptamine (5-HT, serotonin), kynurenine (Kyn), and various indole derivatives. It has been revealed that a substantial correlation exists between alterations in Trp metabolism and the initiation and progression of metabolic disorders, including obesity, diabetes, non-alcoholic fatty liver disease, and atherosclerosis, but Trp metabolites have not been comprehensively reviewed in metabolic diseases. As such, this review summarizes and analyzes the latest research, emphasizing the importance of further studying Trp metabolism within the gut microbiota to understand and treat metabolic diseases. This carries potential significance for improving human health and may introduce new therapeutic strategies.

6.
J Environ Manage ; 370: 122542, 2024 Sep 22.
Article in English | MEDLINE | ID: mdl-39312876

ABSTRACT

Antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs) are emerging contaminants that widely exist in the environment. Effective reduction of ARB and ARGs from soil and water could be achieved by electrokinetic remediation (EKR) technology. In water, hydroxyl radicals (·OH) are proved to play a major role in the EKR process; while the reduction mechanism of ARB and ARGs is still unclear in soil. In this study, different concentrations of hydroxyl radical scavengers (salicylic acid) were added to the EKR system to explore the possible role of ·OH in the reduction of ARB and ARGs. The results showed that generally, ·OH played a more vital role in the reduction of ARB (65.24-72.46%) compared to the reduction of total cultivable bacteria (57.50%). And ·OH contributed to a higher reduction of sul genes (60.94%) compared to tet genes (47.71%) and integrons (36.02%). It was found that the abundance of Gram-negative bacteria (Chloroflexi, Acidobacteria and norank_c_Acidobacteria) was significantly reduced, and the correlation between norank_f_Gemmatimonadaceae and sul1 was weakened in the presence of ·OH. Correlation analysis indicated that the abundance of ARGs (especially sul1) was closely related to the Gram-negative bacteria (Proteobacteria, Acidobacteria, and Gemmatimonadetes) in the soil EKR treatment. Moreover, changes in bacterial community structure affected the abundance of ARB and ARGs indirectly. Overall, this study revealed the reduction mechanism of ARB and ARGs by ·OH in the soil EKR system for the first time. These findings provide valuable support for soil remediation efforts focusing on controlling antibiotic resistance.

7.
Small Methods ; : e2400460, 2024 Sep 09.
Article in English | MEDLINE | ID: mdl-39248667

ABSTRACT

"Flash heating" that transiently generates high temperatures above 1000 °C has great potential in synthesizing new materials with unprecedently properties. Up to now, the realization of "flash heating" still relies on the external power, which requires sophisticated setups for vast energy input. In this study, a mechanochemically triggered, self-powered flash heating approach is proposed by harnessing the enthalpy from chemical reactions themselves. Through a model reaction between Mg3N2/carbon and P2O5, it is demonstrated that this self-powered flash heating is controllable and compatible with conventional devices. Benefit from the self-powered flash heating, the resulting product has a nanoporous structure with a uniform distribution of phosphorus (P) nanoparticles in carbon (C) nanobowls with strong P─-C bonds. Consequently, the P/C composite demonstrates remarkable energy storage performance in lithium-ion batteries, including high capacity (1417 mAh g-1 at 0.2 A g-1), robust cyclic stability (935 mAh g-1 at 2 A g-1 after 800 cycles, 91.6% retention), high-rate capability (739 mAh g-1 at 20 A g-1), high loading performance (3.6 mAh cm-2 after 100 cycles), and full cell cyclic stability (90% retention after 100 cycles). This work broadens the flash heating concept and can potentially find application in various fields.

8.
Neuroimage ; 300: 120789, 2024 Oct 15.
Article in English | MEDLINE | ID: mdl-39159702

ABSTRACT

Interpersonal emotion regulation (IER) is a crucial ability for effectively recovering from negative emotions through social interaction. It has been emphasized that the empathy network, cognitive control network, and affective generation network sustain the deployment of IER. However, the temporal dynamics of functional connectivity among these networks of IER remains unclear. This study utilized IER task-fMRI and sliding window approach to examine both the stationary and dynamic functional connectivity (dFC) of IER. Fifty-five healthy participants were recruited for the present study. Through clustering analysis, four distinct brain states were identified in dFC. State 1 demonstrated situation modification stage of IER, with strong connectivity between affective generation and visual networks. State 2 exhibited pronounced connectivity between empathy network and both cognitive control and affective generation networks, reflecting the empathy stage of IER. Next, a 'top-down' pattern is observed between the connectivity of cognitive control and affective generation networks during the cognitive control stage of state 3. The affective response modulation stage of state 4 mainly involved connections between empathy and affective generation networks. Specifically, the degree centrality of the left middle temporal gyrus (MTG) mediated the association between one's IER tendency and the regulatory effects in state 2. The betweenness centrality of the left ventrolateral prefrontal cortex (VLPFC) mediated the association between one's IER efficiency and the regulatory effects in state 3. Altogether, these findings revealed that dynamic connectivity transitions among empathy, cognitive control, and affective generation networks, with the left VLPFC and MTG playing dominant roles, evident across the IER processing.


Subject(s)
Emotional Regulation , Magnetic Resonance Imaging , Prefrontal Cortex , Temporal Lobe , Humans , Male , Prefrontal Cortex/physiology , Prefrontal Cortex/diagnostic imaging , Female , Young Adult , Adult , Emotional Regulation/physiology , Temporal Lobe/physiology , Temporal Lobe/diagnostic imaging , Empathy/physiology , Brain Mapping/methods , Interpersonal Relations , Nerve Net/physiology , Nerve Net/diagnostic imaging , Connectome/methods , Emotions/physiology
9.
Ann Med ; 56(1): 2388709, 2024 Dec.
Article in English | MEDLINE | ID: mdl-39155811

ABSTRACT

BACKGROUND: To construct and evaluate a predictive model for in-hospital mortality among critically ill patients with acute kidney injury (AKI) undergoing continuous renal replacement therapy (CRRT), based on nine machine learning (ML) algorithm. METHODS: The study retrospectively included patients with AKI who underwent CRRT during their initial hospitalization in the United States using the medical information mart for intensive care (MIMIC) database IV (version 2.0), as well as in the intensive care unit (ICU) of Huzhou Central Hospital. Patients from the MIMIC database were used as the training cohort to construct the models (from 2008 to 2019, n = 1068). Patients from Huzhou Central Hospital were utilized as the external validation cohort to evaluate the models (from June 2019 to December 2022, n = 327). In the training cohort, least absolute shrinkage and selection operator (LASSO) regression with cross-validation was employed to select features for constructing the model and subsequently established nine ML predictive models. The performance of these nine models on the external validation cohort dataset was comprehensively evaluated based on the area under the receiver operating characteristic curve (AUROC) and the optimal model was selected. A static nomogram and a web-based dynamic nomogram were presented, with a comprehensive evaluation from the perspectives of discrimination (AUROC), calibration (calibration curve) and clinical practicability (DCA curves). RESULTS: Finally, 1395 eligible patients were enrolled, including 1068 patients in the training cohort and 327 patients in the external validation cohort. In the training cohort, LASSO regression with cross-validation was employed to select features and nine models were individually constructed. Compared to the other eight models, the Lasso regularized logistic regression (Lasso-LR) model exhibited the highest AUROC (0.756) and the optimal calibration curve. The DCA curve suggested a certain clinical utility in predicting in-hospital mortality among critically ill patients with AKI undergoing CRRT. Consequently, the Lasso-LR model was the optimal model and it was visualized as a common nomogram (static nomogram) and a web-based dynamic nomogram (https://chsyh2006.shinyapps.io/dynnomapp/). Discrimination, calibration and DCA curves were employed to assess the performance of the nomogram. The AUROC for the training and external validation cohorts in the nomogram model was 0.771 (95%CI: 0.743, 0.799) and 0.756 (95%CI: 0.702, 0.809), respectively. The calibration slope and Brier score for the training cohort were 1.000 and 0.195, while for the external validation cohort, they were 0.849 and 0.197, respectively. The DCA indicated that the model had a certain clinical application value. CONCLUSIONS: Our study selected the optimal model and visualized it as a static and dynamic nomogram integrating clinical predictors, so that clinicians can personalized predict the in-hospital outcome of critically ill patients with AKI undergoing CRRT upon ICU admission.


Subject(s)
Acute Kidney Injury , Continuous Renal Replacement Therapy , Hospital Mortality , Machine Learning , Humans , Acute Kidney Injury/mortality , Acute Kidney Injury/therapy , Male , Female , Continuous Renal Replacement Therapy/methods , Middle Aged , Retrospective Studies , Aged , Critical Illness/mortality , Critical Illness/therapy , Nomograms , Algorithms , Intensive Care Units/statistics & numerical data , ROC Curve , Risk Assessment/methods , United States/epidemiology
10.
Nat Nanotechnol ; 2024 Aug 20.
Article in English | MEDLINE | ID: mdl-39164411

ABSTRACT

Microstrain and the associated surface-to-bulk propagation of structural defects are known to be major roadblocks to developing high-energy and long-life batteries. However, the origin and effects of microstrain during the synthesis of battery materials remain largely unknown. Here we perform microstrain screening during real-time and realistic synthesis of sodium layered oxide cathodes. Evidence gathered from multiscale in situ synchrotron X-ray diffraction and microscopy characterization collectively reveals that the spatial distribution of transition metals within individual precursor particles strongly governs the nanoscale phase transformation, local charge heterogeneity and accumulation of microstrain during synthesis. This unexpected dominance of transition metals results in a counterintuitive outward propagation of defect nucleation and growth. These insights direct a more rational synthesis route to reduce the microstrain and crystallographic defects within the bulk lattice, leading to significantly improved structural stability. The present work on microstrain screening represents a critical step towards synthesis-by-design of defect-less battery materials.

11.
Front Immunol ; 15: 1430070, 2024.
Article in English | MEDLINE | ID: mdl-39188727

ABSTRACT

Lymphoma is a highly heterogeneous lymphohematopoietic tumor. As our understanding of the biological and pathological characteristics of lymphoma improves, we are identifying an increasing number of lymphoma subtypes. Genotyping has enhanced our ability to diagnose, treat, and monitor the prognosis of lymphoma. Despite significant improvements in treatment effectiveness, traditional methods for assessing disease response and monitoring prognosis are imperfect, and there is no significant improvement in overall remission rates for lymphoma patients. Minimal Residual Disease (MRD) is often indicative of refractory disease or early relapse. For lymphoma patients, personalized MRD monitoring techniques offer an efficient means to estimate disease remission levels, predict early relapse risk, and assess the effectiveness of new drug regimens. In this review, we delve into the MRD procedures in lymphoma, including sample selection and requirements, detection methods and their limitations and advantages, result interpretation. Besides, we also introduce the clinical applications of MRD detection in lymphoma.


Subject(s)
Lymphoma , Neoplasm, Residual , Neoplasm, Residual/diagnosis , Humans , Lymphoma/diagnosis , Prognosis , Biomarkers, Tumor , Clinical Relevance
12.
Nat Commun ; 15(1): 6084, 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39030160

ABSTRACT

Tuning the properties of a pair of entangled electron and hole in a light-induced exciton is a fundamentally intriguing inquiry for quantum science. Here, using semiconducting hybrid perovskite as an exploratory platform, we discover that Nd2+-doped CH3NH3PbI3 (MAPbI3) perovskite exhibits a Kondo-like exciton-spin interaction under cryogenic and photoexcitation conditions. The feedback to such interaction between excitons in perovskite and the localized spins in Nd2+ is observed as notably prolonged carrier lifetimes measured by time-resolved photoluminescence, ~10 times to that of pristine MAPbI3 without Nd2+ dopant. From a mechanistic standpoint, such extended charge separation states are the consequence of the trap state enabled by the antiferromagnetic exchange interaction between the light-induced exciton and the localized 4 f spins of the Nd2+ in the proximity. Importantly, this Kondo-like exciton-spin interaction can be modulated by either increasing Nd2+ doping concentration that enhances the coupling between the exciton and Nd2+ 4 f spins as evidenced by elongated carrier lifetime, or by using an external magnetic field that can nullify the spin-dependent exchange interaction therein due to the unified orientations of Nd2+ spin angular momentum, thereby leading to exciton recombination at the dynamics comparable to pristine MAPbI3.

13.
Environ Sci Pollut Res Int ; 31(32): 44983-44994, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38955967

ABSTRACT

Elemental doping is a promising way for enhancing the electrocatalytic activity of metal oxides. Herein, we fabricate Ti/ Ti4O7-CB-Ce anode materials by the modification means of carbon black and cerium co-doped Ti4O7, and this shift effectively improves the interfacial charge transfer rate of Ti4O7 and •OH yield in the electrocatalytic process. Remarkably, the Ti4O7-CB-Ce anode exhibits excellent efficiency of minocycline (MNC) wastewater treatment (100% removal within 20 min), and the removal rate reduces from 100 to 98.5% after five cycles, which is comparable to BDD electrode. •OH and 1O2 are identified as the active species in the reaction. Meanwhile, it is discovered that Ti/ Ti4O7-CB-Ce anodes can effectively improve the biochemical properties of the non-biodegradable pharmaceutical wastewater (B/C values from 0.25 to 0.44) and significantly reduce the toxicity of the wastewater (luminescent bacteria inhibition rate from 100 to 26.6%). This work paves an effective strategy for designing superior metal oxides electrocatalysts.


Subject(s)
Anti-Bacterial Agents , Cerium , Oxidation-Reduction , Soot , Wastewater , Cerium/chemistry , Anti-Bacterial Agents/chemistry , Wastewater/chemistry , Catalysis , Soot/chemistry , Electrodes , Titanium/chemistry , Tetracycline/chemistry , Water Pollutants, Chemical/chemistry
14.
Discov Oncol ; 15(1): 279, 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38995414

ABSTRACT

Acute myeloid leukemia (AML) is one of the most common hematopoietic malignancies that has a poor prognosis and a high rate of relapse. Dysregulated metabolism plays an important role in AML progression. This study aimed to conduct a comprehensive analysis of MRGs using TCGA and GEO datasets and further explore the potential function of critical MRGs in AML progression. In this study, we identified 17 survival-related differentially expressed MRGs in AML using TCGA and GEO datasets. The 150 AML samples were divided into three molecular subtypes using 17 MRGs, and we found that three molecular subtypes exhibited a different association with ferroptosis, cuproptosis and m6A related genes. Moreover, a prognostic signature that comprised nine MRGs and had good predictive capacity was established by LASSO-Cox stepwise regression analysis. Among the 17 MRGs, our attention focused on MICAL1 which was highly expressed in many types of tumors, including AML and its overexpression was also confirmed in several AML cell lines. We also found that the expression of MICAL1 was associated with several immune cells. Moreover, functional experiments revealed that knockdown of MICAL1 distinctly suppressed the proliferation of AML cells. Overall, this study not only contributes to a deeper understanding of the molecular mechanisms underlying AML but also provides potential targets and prognostic markers for AML treatment. These findings offer robust support for further research into therapeutic strategies and mechanisms related to AML, with the potential to improve the prognosis and quality of life for AML patients. Nevertheless, further research is needed to validate these findings and explore more in-depth molecular mechanisms.

15.
Int J Mol Med ; 54(3)2024 Sep.
Article in English | MEDLINE | ID: mdl-38994756

ABSTRACT

Drug resistance is a key factor underlying the failure of tumor chemotherapy. It enhances the stem­like cell properties of cancer cells, tumor metastasis and relapse. Luteolin is a natural flavonoid with strong anti­tumor effects. However, the mechanism(s) by which luteolin protects against paclitaxel (PTX)­resistant cancer cell remains to be elucidated. The inhibitory effect of luteolin on the proliferation of EC1/PTX and EC1 cells was detected by cell counting kit­8 assay. Colony formation and flow cytometry assays were used to assess clonogenic capacity, cell cycle and apoptosis. Wound healing and Transwell invasion tests were used to investigate the effects of luteolin on the migration and invasion of EC1/PTX cells. Western blotting was used to detect the protein levels of EMT­related proteins and stem cell markers after sphere formation. Parental cells and drug­resistant cells were screened by high­throughput sequencing to detect the differential expression of RNA and differential genes. ELISA and western blotting were used to verify the screened PI3K/Akt signaling pathway, key proteins of which were explored by molecular docking. Hematoxylin and eosin staining and TUNEL staining were used to observe tumor xenografts on morphology and apoptosis in nude mice. The present study found that luteolin inhibited tumor resistance (inhibited proliferation, induced cell cycle arrest and apoptosis and hindered migration invasion, EMT and stem cell spherification) in vitro in PTX­resistant esophageal squamous cell carcinoma (ESCC) cells. In addition, luteolin enhanced drug sensitivity and promoted the apoptosis of drug­resistant ESCC cells in combination with PTX. Mechanistically, luteolin may inhibit the PI3K/AKT signaling pathway by binding to the active sites of focal adhesion kinase (FAK), Src and AKT. Notably, luteolin lowered the tumorigenic potential of PTX­resistant ESCC cells but did not show significant toxicity in vivo. Luteolin enhanced drug chemosensitivity by downregulating the FAK/PI3K/AKT pathway in PTX­resistant ESCC and could be a promising agent for the treatment of PTX­resistant ESCC cancers.


Subject(s)
Drug Resistance, Neoplasm , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Luteolin , Paclitaxel , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Signal Transduction , Luteolin/pharmacology , Paclitaxel/pharmacology , Drug Resistance, Neoplasm/drug effects , Humans , Proto-Oncogene Proteins c-akt/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Animals , Cell Line, Tumor , Esophageal Squamous Cell Carcinoma/drug therapy , Esophageal Squamous Cell Carcinoma/metabolism , Esophageal Squamous Cell Carcinoma/pathology , Esophageal Squamous Cell Carcinoma/genetics , Signal Transduction/drug effects , Mice , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/metabolism , Esophageal Neoplasms/pathology , Mice, Nude , Cell Movement/drug effects , Focal Adhesion Kinase 1/metabolism , Focal Adhesion Kinase 1/genetics , Apoptosis/drug effects , Cell Proliferation/drug effects , Down-Regulation/drug effects , Mice, Inbred BALB C , Xenograft Model Antitumor Assays , Antineoplastic Agents, Phytogenic/pharmacology , Gene Expression Regulation, Neoplastic/drug effects , Epithelial-Mesenchymal Transition/drug effects , Female , Male
16.
Int J Biol Macromol ; 277(Pt 1): 134024, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39032899

ABSTRACT

Silicosis is a systemic disease with predominantly diffuse fibrosis of the lungs due to prolonged inhalation of free SiO2 dust during the manufacturing process, for which there is no effective treatment. In this study, we used a combined epigenetic and transcriptomic approach to reveal the chromatin-opening features of silicosis and identify the key transcription factor activator protein 1 (AP-1) that responds to silicosis fibrosis. Therapeutic administration of an AP-1 inhibitor inhibits the PI3K/AKT signaling pathway, reduces fibrosis marker proteins, and significantly ameliorates lung fibrosis in a mouse model of silicosis. In addition, it was observed that the expression of Jun and JunB was significantly up-regulated in a TGF-ß1-induced in vitro transdifferentiation model of NIH/3T3 cells, and Co-IP confirmed that a protein complex could be formed between Jun and JunB. Mechanistically, silencing of Jun and JunB expression reversed the activation of the PI3K/AKT signaling pathway and the upregulation of fibrosis marker proteins in NIH/3 T3 cells after TGF-ß1 stimulation. Taken together, Jun/JunB is expected to be a potential therapeutic target for silicosis fibrosis.


Subject(s)
Proto-Oncogene Proteins c-jun , Signal Transduction , Silicosis , Transcription Factor AP-1 , Silicosis/metabolism , Silicosis/drug therapy , Silicosis/pathology , Animals , Mice , Transcription Factor AP-1/metabolism , NIH 3T3 Cells , Signal Transduction/drug effects , Proto-Oncogene Proteins c-jun/metabolism , Transforming Growth Factor beta1/metabolism , Humans , Male , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Disease Models, Animal , Transcription Factors/metabolism , Transcription Factors/genetics , Pulmonary Fibrosis/drug therapy , Pulmonary Fibrosis/metabolism , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/pathology , Mice, Inbred C57BL
18.
Chem Biodivers ; : e202401027, 2024 Jul 29.
Article in English | MEDLINE | ID: mdl-39073310

ABSTRACT

Four new prenylated acetophenone derivatives, including one acetophenone dimer [acronyrone D (1)] and three acetophenone monomers [acronyrones E-G (2-4)], along with seven known analogues (5-11) were obtained from the leaves of Acronychia pedunculata. Their structures and absolute configurations were established by analysis of HRMS and NMR data, single crystal X-ray diffraction studies and quantum chemical calculations. In addition, the isolates were tested for their anti-proliferative acivity against HCT-116, RKO and SW480 cancer cell lines. Remarkably, compound 5 exhibited significant anti-proliferative effects on the three cell lines, with IC50 values ranging from 0.24 to 5.3 µM.

19.
World J Urol ; 42(1): 429, 2024 Jul 22.
Article in English | MEDLINE | ID: mdl-39037463

ABSTRACT

PURPOSE: To evaluate the association between serum alpha-fetoprotein (AFP) half-life (HL) and prognosis in prepubertal children with elevated AFP values 3 to 4 weeks after surgery for testicular yolk sac tumors (YST). METHODS: Prepubertal patients with testicular YST treated with radical orchiectomy between January 2016 and December 2022 were retrospectively reviewed. Negative outcomes were defined as relapse, metastasis or death. Univariate and multivariate logistic regression analyses were conducted to select risk factors for negative outcomes. RESULTS: A total of 42 patients were eventually enrolled into the study. Patients were divided into non-negative and negative outcomes groups, consisting of 35 and 7 patients, respectively. Thirty-five patients were stage I, two cases were stage II, and five cases were stage IV, according to the Children's Oncology Group staging system. The overall survival (OS) rate was 100%. Average AFP values significantly decreased after resection (P < 0.001). A significant positive correlation was shown between pre- and postoperative AFP values (r = 0.60, P < 0.001). Long AFP HL was considered as an independent risk factor for negative outcomes in YST patients underwent radical orchiectomy (P = 0.04). The cut-off value for AFP HL was 5.78 days, regardless of age division. CONCLUSION: Testicular YST is a relatively rare disease in children with an OS of 100%, and salvage chemotherapy is effective even in grade IV patients. The postoperative AFP HL was significantly associated with prognosis in prepubertal patients with testicular YST. The cut-off value for AFP HL is 5.78 days regardless of the effect of physiological AFP elevation.


Subject(s)
Endodermal Sinus Tumor , Testicular Neoplasms , alpha-Fetoproteins , Humans , Male , alpha-Fetoproteins/metabolism , alpha-Fetoproteins/analysis , Testicular Neoplasms/blood , Testicular Neoplasms/surgery , Testicular Neoplasms/pathology , Prognosis , Retrospective Studies , Child, Preschool , Child , Endodermal Sinus Tumor/blood , Endodermal Sinus Tumor/surgery , Endodermal Sinus Tumor/pathology , Orchiectomy , Infant
20.
Chem Commun (Camb) ; 60(56): 7192-7195, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38904432

ABSTRACT

A bipolar polymer cathode material, containing redox-active azo benzene and diamine moieties, was synthesized for sodium-ion batteries. The n-type azo group and p-type amine group enable a wide cutoff window with an initial capacity of 93 mA h g-1 at 50 mA g-1 and a high voltage plateau at ∼3.3 V.

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