ABSTRACT
The α-diimine-ligated Zn-Zn-bonded compound [K(THF)2]2[LZn-ZnL] (1, L = [(2,6-iPr2C6H3)NC(Me)]22-) displays diverse reactivities toward a variety of ketones. In the reaction of 1 with benzophenone or 4,4'-di-tert-butylbenzophenone, a multielectron transfer process was observed to give bimetallic (Zn/K) complexes with both ketyl radical fragments and C-C coupled pinacolate moieties (products 2 and 3). In contrast, treating 1 with 9-fluorenone only afforded pinacolate complex 5. Moreover, the reactions of 1 with N- or O-heterocycle-functionalized ketones, i.e., di(2-pyridyl)ketone, 2,2-pyrrolidinone, 9-xanthenone, or 10-methyl-9(10H)-acridone, were also carried out. Besides different transformations of the ketone moiety, the heteroatoms (nitrogen or oxygen) are also involved in coordination with zinc or potassium ions, yielding discrete aggregates or polymeric structures of products 6-9.
ABSTRACT
BACKGROUND: Oxidative stress is a well-known pathological factor driving neuronal loss and age-related neurodegenerative diseases. Melatonin, coenzyme Q10 and lecithin are three common nutrients with an antioxidative capacity. Here, we examined the effectiveness of them administrated individually and in combination in protecting against oxidative stress-induced neuronal death in vitro, and neurodegenerative conditions such as Alzheimer's disease and associated deficits in vivo. METHODS: Mouse neuroblastoma Neuro-2a (N2a) cells were exposed with H2O2 for 6 h, and subsequently treated with melatonin, coenzyme Q10, and lecithin alone or in combination for further 24 h. Cell viability was assessed using the CCK-8 assay. Eight-week-old male mice were intraperitoneally injected with D-(+)-galactose for 10 weeks and administrated with melatonin, coenzyme Q10, lecithin, or in combination for 5 weeks starting from the sixth week, followed by behavioral tests to assess the effectiveness in mitigating neurological deficits, and biochemical assays to explore the underlying mechanisms. RESULTS: Exposure to H2O2 significantly reduced the viability of N2a cells and increased oxidative stress and tau phosphorylation, all of which were alleviated by treatment with melatonin, coenzyme Q10, lecithin alone, and, most noticeably, by combined treatment. Administration of mice with D-(+)-galactose-induced oxidative stress and tau phosphorylation, brain aging, impairments in learning and memory, anxiety- and depression-like behaviors, and such detrimental effects were mitigated by melatonin, coenzyme Q10, lecithin alone, and, most consistently, by combined treatment. CONCLUSIONS: These results suggest that targeting oxidative stress via supplementation of antioxidant nutrients, particularly in combination, is a better strategy to alleviate oxidative stress-mediated neuronal loss and brain dysfunction due to age-related neurodegenerative conditions.
Subject(s)
Antioxidants , Hydrogen Peroxide , Neurons , Oxidative Stress , Ubiquinone , Animals , Oxidative Stress/drug effects , Mice , Ubiquinone/analogs & derivatives , Ubiquinone/pharmacology , Ubiquinone/administration & dosage , Male , Antioxidants/pharmacology , Hydrogen Peroxide/toxicity , Neurons/drug effects , Neurons/pathology , Cell Line, Tumor , Melatonin/pharmacology , Melatonin/therapeutic use , Cell Survival/drug effects , Cell Survival/physiology , tau Proteins/metabolism , Neuroprotective Agents/pharmacology , Galactose/toxicity , Drug Therapy, CombinationABSTRACT
Heavy metal accumulation in agricultural products has become a major concern. Previous studies have focused on the transport of heavy metals from the soil and their accumulation in crops. However, recent studies revealed that wheat leaves, ears, and awns can also transport and accumulate heavy metals. Wheat grains can be influenced by two sources of heavy metals: soil contamination and atmospheric deposition. To comprehend the transport characteristics of heavy metals in soil, atmospheric deposition, and wheat, 37 samples each for wheat rhizosphere soil, wheat roots, stems, leaves, and grains were collected. Fifteen samples of atmospheric dry deposition and atmospheric wet deposition were collected from Linshu County (northern area), China. Based on the test data, the characteristics of heavy metals and their distribution in the study area were analyzed. Migration patterns of heavy metals in crops from different sources were investigated using Pearson correlation and redundancy analysis. Finally, a predictive model for heavy metals in wheat grains was developed using multiple linear regression analysis. Significant disparities in the distribution of heavy metals existed among wheat roots, stems, leaves, and grains. The coefficient of variation of heavy metals in atmospheric deposition was relatively high, indicating discernible spatial patterns influenced by human activities. Notably, a positive correlation was observed between the concentration of heavy metals in wheat grains and atmospheric deposition of Hg, Cd, and Pb. Conversely, Zn and Ni levels in wheat grains were significantly negatively associated with soil Zn, Ni, pH, and OM content. The contribution of heavy metal elements from different sources varied in their impact on the grain's heavy metal content. Specifically, atmospheric deposition was the primary source of Hg and Pb in wheat grains, while Cd, Ni, Cu, and Zn were predominantly derived from soil. Using a multiple linear regression model, we could accurately predict Hg, Pb, Cd, Ni, Zn, and As concentrations in crop grains. This model can facilitate quantitative evaluation of ecological risk of heavy metals accumulation in crops in the study area.
Subject(s)
Metals, Heavy , Soil Pollutants , Soil , Triticum , Triticum/metabolism , Triticum/chemistry , Triticum/growth & development , Metals, Heavy/analysis , Metals, Heavy/metabolism , Soil Pollutants/analysis , Soil Pollutants/metabolism , Soil/chemistry , Linear Models , China , Agriculture/methods , Atmosphere/chemistry , Crops, Agricultural/metabolism , Crops, Agricultural/chemistry , Crops, Agricultural/growth & development , Environmental Monitoring/methods , Plant Leaves/metabolism , Plant Leaves/chemistry , Plant Roots/metabolism , Plant Roots/chemistryABSTRACT
Heteroleptic, bimetallic (Mg/K) cyclopentadienyl complexes (2-4) were synthesized by the reaction of the Mg-Mg-bonded compound [K(THF)3]2[LMg-MgL] (1, L = [(2,6-iPr2C6H3)NC(CH3)]22-) with cyclopentadiene derivatives, 6,6-dimethylfulvene, 6-(dimethylamino)fulvene, or 1,2,3,4-tetramethyl-1,3-cyclopentadiene. The reactions proceed through diverse pathways, including hydrogen abstraction, C-C coupling, and dehydrogenation, depending on the property of the polyene substrate, thus providing an access to alkali/alkaline earth metal cyclopentadienyl complexes.
ABSTRACT
Tau protein hyperphosphorylation and formation of intracellular neurofibrillary tangles (NFTs) are one of the histopathological hallmarks of Alzheimer's disease (AD) and positively correlated with the severity of AD symptoms. NFTs contain a large number of metal ions that play an important role in regulating tau protein phosphorylation and AD progression. Extracellular tau induces primary phagocytosis of stressed neurons and neuronal loss by activating microglia. Here, we studied the effects of a multi-metal ion chelator, DpdtpA, on tau-induced microglial activation and inflammatory responses and the underlying mechanisms. Treatment with DpdtpA attenuated the increase in the expression of NF-κB and production of inflammatory cytokines, IL-1ß, IL-6 and IL-10, in rat microglial cells induced by expression of human tau40 proteins. Treatment with DpdtpA also suppressed tau protein expression and phosphorylation. Moreover, treatment with DpdtpA prevented tau-induced activation of glycogen synthase kinase-3ß (GSK-3ß) and inhibition of phosphatidylinositol-3-hydroxy kinase (PI3K)/AKT. Collectively, these results show that DpdtpA can attenuate tau phosphorylation and inflammatory responses of microglia by regulating the PI3K/AKT/GSK-3ß signal pathways, providing a new option to alleviate neuroinflammation for the treatment of AD.
Subject(s)
Alzheimer Disease , tau Proteins , Rats , Humans , Animals , tau Proteins/metabolism , Phosphatidylinositol 3-Kinase/metabolism , Phosphatidylinositol 3-Kinase/pharmacology , Phosphorylation , Microglia/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Glycogen Synthase Kinase 3 beta/metabolism , Signal Transduction , Alzheimer Disease/metabolism , Chelating Agents/pharmacologyABSTRACT
OBJECTIVES: The objective was to calculate the efficacy of ultrasonographically-based measurements of minimum and maximum fascia-tumor distance (MiFTD and MaFTD) of benign salivary gland tumors to identify tumor location in the superficial or deep lobe of the parotid gland. STUDY DESIGN: MiFTDs and MaFTDs were measured on pre-operative ultrasonographic images of 102 tumors. Tumor location was classified at surgery as superficial or deep based on relation to the facial nerve, with 74 tumors in the superficial lobe and 28 in the deep lobe. The diagnostic efficacy of differences in MiFTD and MaFTD between locations was calculated with the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. Statistical significance was established at P < .05. RESULTS: Mean MiFTD and MaFTD values were significantly smaller in the superficial lobe tumors than in the deep lobe lesions (P < .001). Tumors with cutoff values of MiFTD >2.7 mm or MaFTD >21.1 mm were considered deep lobe lesions. When using the cutoff values for both MiFTD and MaFTD, the AUC was 0.893, whereas sensitivity and specificity were .821 and .919, respectively. CONCLUSIONS: Ultrasonography can help in the preoperative localization of tumors in the superficial and deep lobes of the parotid gland. This can facilitate proper surgical treatment selection and minimize the risk of adverse consequences of facial nerve damage while improving cosmetic outcomes.
Subject(s)
Parotid Neoplasms , Humans , Parotid Neoplasms/diagnostic imaging , Parotid Neoplasms/surgery , Retrospective Studies , Parotid Gland/diagnostic imaging , Parotid Gland/surgery , Parotid Gland/pathology , Sensitivity and Specificity , Facial NerveABSTRACT
Gasdermin D-executing pyroptosis mediated by NLRP3 inflammasomes has been recognized as a key pathogenesis during stroke. Hydrogen sulfide (H2S) could protect CNS against ischemia/reperfusion (I/R)-induced neuroinflammation, while the underlying mechanism remains unclear. The study applied the middle cerebral artery occlusion/reperfusion (MCAO/R) model to investigate how the brain and the retinal injuries were alleviated in sodium hydrogen sulfide (NaHS)-treated rats. The rats were assigned to four groups and received an intraperitoneal injection of 50 µmol/kg NaHS or NaCl 15 min after surgery. Neurological deficits were evaluated using the modified neurologic severity score. The quantification of pro-inflammatory cytokines, NLRP3, caspase-1, and GSDMD were determined by ELISA and Western blot. Cortical and retinal neurodegeneration and cell pyroptosis were determined by histopathologic examination. Results showed that NaHS rescued post-stroke neurological deficits and infarct progression, improved retina injury, and attenuated neuroinflammation in the brain cortexes and the retinae. NaHS administration inhibits inflammation by blocking the NLRP3/caspase-1/GSDMD pathway and further suppressing neuronal pyroptosis. This is supported by the fact that it reversed the high-level of NLRP3, caspase-1, and GSDMD following I/R. Our findings suggest that compounds with the ability to donate H2S could constitute a novel therapeutic strategy for ischemic stroke.
ABSTRACT
Six Cu(i) complexes, [Cu(2,3-f)(bdppmapy)]BF4 (1), [Cu(2,3-f)(bdppmapy)]ClO4 (2), [Cu(2,3-f)(bdppmapy)]CF3SO3 (3), [Cu(imidazo[4,5-f])(bdppmapy)]BF4 (4), [Cu(imidazo[4,5-f])(bdppmapy)]ClO4 (5), and [Cu(imidazo[4,5-f])(bdppmapy)]CF3SO3·MeOH (6·MeOH) (bdppmapy = N,N-bis[(diphenylphosphino)methyl]-2-pyridinamine, 2,3-f = pyrazine[2,3-f][1,10]-phenanthroline, and imidazo[4,5-f] = 1H-imidazo[4,5-f][1,10]-phenanthroline), have been synthesized to explore the effects of counteranions on their crystal structures, photophysical properties, and terahertz (THz) spectra. Time-dependent density functional theory (TD-DFT) shows that the luminescence performance of these complexes is attributed to the metal-to-ligand charge transfer (MLCT) in combination with ligand-to-ligand charge transfer (LLCT). In complexes 1-3, the characteristic peak at 1.4 THz is mainly related to the C-Hπ interaction formed by the H atom on the 4#/5# position of 2,3-f and the benzene ring from the bdppmapy on the adjacent asymmetric unit. The common C-Hπ interaction enhances the rigidity of the structure and has non-negligible influence on the photoluminescence quantum yields (PLQYs): the stronger the C-Hπ interaction is, the higher the quantum yield (QY) is. In complexes 4-6, similar absorption peaks (1.10-1.30 THz) are mainly related to the C-Hπ interactions, and strong absorption peaks (1.50-1.90 THz) are affected by the typical hydrogen bonds N-HF/O and O-HO. These results show that some weak interactions can be characterized by THz time-domain spectroscopy (THz-TDS). So, the THz spectroscopy method would make it possible to tune some of the weak interactions in complex structures to regulate the luminescence of materials.
ABSTRACT
Acute lung injury (ALI) caused by gas explosion is common, and warrants research on the underlying mechanisms. Specifically, the role of abnormalities of coagulation and fibrinolysis in this process has not been defined. It was hypothesized that the abnormal coagulation and fibrinolysis promoted ALI caused by gas explosion. Based on the presence of ALI, 74 cases of gas explosion injury were divided into the ALI and non-ALI groups. The results of prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), and platelet count (PLT) were collected within 24 hours and compared between the groups. ALI models caused by gas explosion were established in Sprague Dawley rats, and injuries were evaluated using hematoxylin and eosin (HE) staining and histopathological scoring. Moreover, the bronchoalveolar lavage fluid (BALF) was collected to examine thrombin-antithrombin complex (TAT), tissue factor (TF), tissue factor pathway inhibitor (TFPI), and plasminogen activator inhibitor-1 (PAI-1) levels by enzyme-linked immunosorbent assay (ELISA). The patients in ALI group had shorter PT and longer APTT, raised concentration of FIB and decreased number of PLT, as compared to the non-ALI group. In ALI rats, the HE staining revealed red blood cells in alveoli and interstitial thickening within 2 hours which peaked at 72 hours. The levels of TAT/TF in the BALF increased continually until the seventh day, while the PAI-1 was raised after 24 hours and 7 days. The TFPI was elevated after 2 hours and 24 hours, and then decreased after 72 hours. Abnormalities in coagulation and fibrinolysis in lung tissues play a role in ALI caused by gas explosion.