-
Neuroimmunomodulation 2024Dimethyl fumarate (DMF) has shown potential for protection in various animal models of neurological diseases. However, the impact of DMF on changes in peripheral immune...
INTRODUCTION
Dimethyl fumarate (DMF) has shown potential for protection in various animal models of neurological diseases. However, the impact of DMF on changes in peripheral immune organs and the central nervous system (CNS) immune cell composition after ischemic stroke remains unclear.
METHODS
Eight-week-old C57BL/6J mice with photothrombosis ischemia and patients with acute ischemic stroke (AIS) were treated with DMF. TTC staining, flow cytometry, and immunofluorescence staining were used to evaluate the infarct volume and changes in immune cells in the periphery and the CNS.
RESULTS
DMF reduced the infarct volume on day 1 after PT. DMF reduced the percentages of peripheral immune cells, such as neutrophils, dendritic cells, macrophages, and monocytes, on day 1, followed by NK cells on day 3 and B cells on day 7 after PT. In the CNS, DMF significantly reduced the percentage of monocytes in the brain on day 3 after PT. In addition, DMF increased the number of microglia in the peri-infarct area and reduced the number of neurons in the peri-infarct area in the acute and subacute phases after PT. In AIS patients, B cells decreased in patients receiving alteplase in combination with DMF.
CONCLUSION
DMF can change the immune environment of the periphery and the CNS, reduce infarct volume in the acute phase, promote the recruitment of microglia and preserve neurons in the peri-infarct area after ischemic stroke.
Topics: Animals; Dimethyl Fumarate; Ischemic Stroke; Mice, Inbred C57BL; Mice; Male; Humans; Female; Prognosis; Middle Aged; Aged; Disease Models, Animal
PubMed: 38843787
DOI: 10.1159/000539589 -
Bioorganic & Medicinal Chemistry Jun 2024An efficient protocol for direct coupling of maleimides and indolines at the C7-position was achieved under Rh(III) catalysis. Thirty four novel indoline-maleimide...
An efficient protocol for direct coupling of maleimides and indolines at the C7-position was achieved under Rh(III) catalysis. Thirty four novel indoline-maleimide conjugates were prepared in good to excellent yields using this method. All compounds were evaluated for their anti-proliferative effect against colorectal cell lines. Among them, compound 3ab showed the most potent anti-proliferative activity against the CRC cells, and displayed low toxicity in the normal cell. Further investigation indicated that 3ab could effectively suppress the proliferation and migration of CRC cells, along with inducing cell cycle arrest and apoptosis. Mechanistic studies revealed that compound 3ab inhibited the proliferation of CRC cells via suppressing the AKT/GSK-3β pathway. In vivo evaluation demonstrated remarkable antitumor effect of 3ab (10 mg/kg) in the HCT116 xenograft model with no obvious toxicity, which is superior to that of 5-Fluorouracil (20 mg/kg). Therefore, conjugate 3ab could be considered as a potential CRC therapy agent for further development.
Topics: Humans; Antineoplastic Agents; Colorectal Neoplasms; Indoles; Maleimides; Cell Proliferation; Drug Design; Animals; Structure-Activity Relationship; Drug Screening Assays, Antitumor; Apoptosis; Molecular Structure; Mice; Dose-Response Relationship, Drug; Mice, Nude; Cell Line, Tumor; Mice, Inbred BALB C; Cell Movement
PubMed: 38843656
DOI: 10.1016/j.bmc.2024.117786 -
PloS One 2024Drought stress is a prominent abiotic factor that adversely influences the growth and development of Bupleurum chinense during its seedling stage, negatively impacting...
Drought stress is a prominent abiotic factor that adversely influences the growth and development of Bupleurum chinense during its seedling stage, negatively impacting biomass and secondary metabolite production, thus affecting yield and quality. To investigate the molecular mechanism underlying the response of B. chinense seedlings under drought stress, this study employed comprehensive physiological, transcriptomic, and metabolomic analyses. The results revealed that under drought stress, the root soluble sugar and free proline content in B. chinense seedlings significantly increased, while the activities of SOD, POD, and CAT increased in the leaves. These findings indicate the presence of distinct response mechanisms in B. chinense to cope with drought stress. Integrated analysis further identified significant correlations between genes and metabolites related to amino acid biosynthesis in the leaves, as well as genes and metabolites associated with acetaldehyde and dicarboxylic acid metabolism. In the roots, genes and metabolites related to plant hormone signaling and the tricarboxylic acid (TCA) cycle showed significant correlations. These findings provide vital views into the molecular-level response mechanisms of B. chinense under drought stress. Moreover, this study establishes the groundwork for identifying drought-tolerant genes and breeding drought-resistant varieties, which could improve the drought tolerance of medicinal plants and have broader implications for agriculture and crop production in water-scarce areas.
Topics: Bupleurum; Seedlings; Droughts; Stress, Physiological; Metabolomics; Gene Expression Regulation, Plant; Transcriptome; Plant Roots; Plant Leaves; Gene Expression Profiling; Metabolome
PubMed: 38843246
DOI: 10.1371/journal.pone.0304503 -
Calcium phosphate controls nucleation and growth of calcium oxalate crystal phases in kidney stones.Biomedical Research (Tokyo, Japan) 2024Kidney stone disease is a serious disease due to the severe pain it causes, high morbidity, and high recurrence rate. Notably, calcium oxalate stones are the most common...
Kidney stone disease is a serious disease due to the severe pain it causes, high morbidity, and high recurrence rate. Notably, calcium oxalate stones are the most common type of kidney stone. Calcium oxalate appears in two forms in kidney stones: the stable phase, monohydrate (COM), and the metastable phase, dihydrate (COD). Particularly, COM stones with concentric structures are hard and difficult to treat. However, the factor determining the growth of either COM or COD crystals in the urine, which is supersaturated for both phases, remains unclear. This study shows that calcium phosphate ingredients preferentially induce COM crystal nucleation and growth, by observing and analyzing kidney stones containing both COM and COD crystals. The forms of calcium phosphate are not limited to Randall's plaques (1-2 mm size aggregates, which contain calcium phosphate nanoparticles and proteins, and form in the renal papilla). For example, aggregates of strip-shaped calcium phosphate crystals and fields of dispersed calcium phosphate microcrystals (nano to micrometer order) also promote the growth of concentric COM structures. This suggests that patients who excrete urine with a higher quantity of calcium phosphate crystals may be more prone to forming hard and troublesome COM stones.
Topics: Calcium Phosphates; Calcium Oxalate; Kidney Calculi; Crystallization; Humans; Animals
PubMed: 38839353
DOI: 10.2220/biomedres.45.103 -
BMC Psychiatry Jun 2024Malignant hyperthermia is a potentially lethal condition triggered by specific anesthetic drugs, especially a depolarizing muscle relaxant of succinylcholine...
BACKGROUND
Malignant hyperthermia is a potentially lethal condition triggered by specific anesthetic drugs, especially a depolarizing muscle relaxant of succinylcholine (Suxamethonium). Despite the frequent use of succinylcholine with electroconvulsive therapy (ECT), there has been no reported case of potentially lethal malignant hyperthermia following ECT. In addition, the time interval between the administration of succinylcholine and the onset of malignant hyperthermia has not been outlined in the context of ECT.
CASE PRESENTATION
We present the case of a 79-year-old woman suffering from severe depression, who experienced severe malignant hyperthermia due to succinylcholine administration during an ECT session. She presented with a high fever of 40.2 °C, tachycardia of 140/min, hypertension with a blood pressure exceeding 200 mmHg, significant muscle rigidity, and impaired consciousness. These symptoms emerged two hours after ECT, which occurred in a psychiatric ward rather than an operating room, and reached their peak in less than 24 h. She was given 60 mg of dantrolene, which quickly reduced the muscular rigidity. Subsequently, she received two additional doses of 20 mg and 60 mg of dantrolene, which brought her fever down to 36.2 °C and completely eased her muscle rigidity within two days after ECT.
CONCLUSIONS
This is the first reported case of potentially lethal malignant hyperthermia after ECT. In addition, it highlights the delayed onset of malignant hyperthermia following an ECT procedure, emphasizing the necessity for psychiatrists to recognize its onset even after the treatment. In the light of potentially lethal consequences of malignant hyperthermia, it is critically important for psychiatrists to closely monitor both intraoperative and postoperative patient's vital signs and characteristic physical presentations, promptly identify any symptomatic emergence, and treat it immediately with dantrolene.
Topics: Humans; Succinylcholine; Electroconvulsive Therapy; Aged; Malignant Hyperthermia; Female; Neuromuscular Depolarizing Agents; Dantrolene; Psychiatrists
PubMed: 38834964
DOI: 10.1186/s12888-024-05846-5 -
Journal of Natural Products Jun 2024Phenazines are aromatic compounds with antifungal and cytotoxic activities. Phenazines incorporating phenazine 1-carboxylic acid have widespread applications in...
Phenazines are aromatic compounds with antifungal and cytotoxic activities. Phenazines incorporating phenazine 1-carboxylic acid have widespread applications in agriculture, medicine, and industry. Griseoluteic acid is a cytotoxic compound secreted by P510, displaying potential medical applications. However, the biosynthetic pathway of griseoluteic acid has not been elucidated, limiting its development and application. In this study, a conserved phenazine biosynthetic gene cluster of P510 was identified through genomic analysis. Subsequently, its was confirmed that the four essential modification enzymes SgpH, SgpI, SgpK, and SgpL convert phenazine-1,6-dicarboxylic acid into griseoluteic acid by heterologous expression in . Moreover, the biosynthetic pathway of griseoluteic acid was established in characterized by a high growth rate and synthesis efficiency of phenazines, laying the foundation for the efficient production of griseoluteic acid.
Topics: Phenazines; Molecular Structure; Multigene Family; Biosynthetic Pathways; Streptomyces; Streptomyces griseus; Pseudomonas chlororaphis; Escherichia coli
PubMed: 38832657
DOI: 10.1021/acs.jnatprod.4c00017 -
RSC Advances May 2024The escalating demand for energy storage underscores the significance of supercapacitors as devices with extended lifespans, high energy densities, and rapid...
The escalating demand for energy storage underscores the significance of supercapacitors as devices with extended lifespans, high energy densities, and rapid charge-discharge capabilities. Ceria (CeO), known for its exceptional properties and dual oxidation states, emerges as a potent material for supercapacitor electrodes. This study enhances its capacitance by integrating it with Metal-Organic Frameworks (MOFs), carbon-rich compounds noted for their good conductivity. In our research, hollow ceria (h-ceria) is synthesized hydrothermal methods and amalgamated with Ce-MOF, employing 2,6-dinaphthalene dicarboxylic acid as a ligand, to fabricate Ce-MOF@h-CeO composites. The structural and morphological characteristics of the composite are methodically examined using X-ray Diffraction (XRD), Field Emission Scanning Electron Microscopy (FE-SEM), and Fourier-Transform Infrared (FT-IR) spectroscopy. The band gap of the materials is ascertained through UV-Diffuse Reflectance Spectroscopy (UV-DRS). Electrochemical behavior and redox properties of the Ce-MOF composites are explored using Cyclic Voltammetry (CV), Galvanostatic Charge and Discharge (GCD), and Electrochemical Impedance Spectroscopy (EIS), providing insights into the material's stability. Electrochemical characterization of the composite reveals maximum specific capacitance, energy density and power density are 2643.78 F g at a scan rate of 10 mV s, 249.22 W h kg, and 7.9 kW kg, respectively. Additionally, the specific capacitance of Ce-MOF synthesized with a 2,6-dinaphthalene dicarboxylic acid (NDC) ligand reaches 995.59 F g, surpassing that of Ce-MOF synthesized using a 1,3,5-tricarboxylic acid (HBTC) ligand. These findings highlight the promising economic potential of high-performance, environmentally sustainable, and cost-effective energy storage devices. The innovative Ce-MOF@h-CeO composite materials at the core of this research pave the way for advancing the field of energy storage solutions.
PubMed: 38832244
DOI: 10.1039/d4ra00523f -
Chemosphere Aug 2024Fe-based metal-organic frameworks (MOFs) have good photocatalytic performance, environmental friendliness, low cost, and abundance. However, their applications are...
Fe-based metal-organic frameworks (MOFs) have good photocatalytic performance, environmental friendliness, low cost, and abundance. However, their applications are limited by low water stability, particularly in the presence of light irradiation and oxidizing agents. In this study, we present a MIL-53(Fe)-based MOF using 1,4-naphthalene dicarboxylic (1,4-NDC) and 1,4-benzenedicarboxylic (HBDC) acid co-ligands, denoted MIL-53(Fe)-N, where N represents the ratio of 1,4-NDC. This MOF exhibits high water stability and good photocatalytic activity because of the hydrophobicity of naphthalene. The removal and mineralization rates for 100 mg/L 2,4-dichlorophenol reached 100% and 22%, respectively, within 60 min. After three cycles of use, the Fe leached into the solution from the catalysts was significantly lower than the maximum permissible limit indicated in the European Union standard. Of note, 1,4-NDC can be used to make a rigid MOF, thereby improving the crystallinity, porosity, and hydrophobicity of the resultant materials. It also significantly reduced the bandgap energy and improved the charge separation efficiency of the catalysts. This study provides a route to enhance the water stability of Fe-based MOFs via a mixed-ligand strategy to expand their applications in pollutant control.
Topics: Metal-Organic Frameworks; Chlorophenols; Catalysis; Water Pollutants, Chemical; Iron; Water; Ligands
PubMed: 38830463
DOI: 10.1016/j.chemosphere.2024.142518 -
PLoS Neglected Tropical Diseases Jun 2024The first dengue outbreak in Sao Tome and Principe was reported in 2022. Entomological investigations were undertaken to establish the typology of Aedes larval habitats,...
BACKGROUND
The first dengue outbreak in Sao Tome and Principe was reported in 2022. Entomological investigations were undertaken to establish the typology of Aedes larval habitats, the distribution of Ae. aegypti and Ae. albopictus, the related entomological risk and the susceptibility profile of Ae. aegypti to insecticides, to provide evidence to inform the outbreak response.
METHODOLOGY/PRINCIPAL FINDINGS
Entomological surveys were performed in all seven health districts of Sao Tome and Principe during the dry and rainy seasons in 2022. WHO tube and synergist assays using piperonyl butoxide (PBO) and diethyl maleate (DEM) were carried out, together with genotyping of F1534C/V1016I/V410L mutations in Ae. aegypti. Aedes aegypti and Ae. albopictus were found in all seven health districts of the country with high abundance of Ae. aegypti in the most urbanised district, Agua Grande. Both Aedes species bred mainly in used tyres, discarded tanks and water storage containers. In both survey periods, the Breteau (BI > 50), house (HI > 35%) and container (CI > 20%) indices were higher than the thresholds established by WHO to indicate high potential risk of dengue transmission. The Ae. aegypti sampled were susceptible to all insecticides tested except dichlorodiphenyltrichloroethane (DDT) (9.2% mortality, resistant), bendiocarb (61.4% mortality, resistant) and alpha-cypermethrin (97% mortality, probable resistant). A full recovery was observed in Ae. aegypti resistant to bendiocarb after pre-exposure to synergist PBO. Only one Ae. aegypti specimen was found carrying F1534C mutation.
CONCLUSIONS/SIGNIFICANCE
These findings revealed a high potential risk for dengue transmission throughout the year, with the bulk of larval breeding occurring in used tyres, water storage and discarded containers. Most of the insecticides tested remain effective to control Aedes vectors in Sao Tome, except DDT and bendiocarb. These data underline the importance of raising community awareness and implementing routine dengue vector control strategies to prevent further outbreaks in Sao Tome and Principe, and elsewhere in the subregion.
Topics: Aedes; Animals; Dengue; Insecticides; Mosquito Vectors; Disease Outbreaks; Insecticide Resistance; Larva; Humans; Piperonyl Butoxide; Female; Maleates; Ecosystem; Dengue Virus
PubMed: 38829904
DOI: 10.1371/journal.pntd.0011903 -
Cell Reports Jun 2024The high infiltration of tumor-associated macrophages (TAMs) in the immunosuppressive tumor microenvironment prominently attenuates the efficacy of immune checkpoint...
The high infiltration of tumor-associated macrophages (TAMs) in the immunosuppressive tumor microenvironment prominently attenuates the efficacy of immune checkpoint blockade (ICB) therapies, yet the underlying mechanisms are not fully understood. Here, we investigate the metabolic profile of TAMs and identify S-2-hydroxyglutarate (S-2HG) as a potential immunometabolite that shapes macrophages into an antitumoral phenotype. Blockage of L-2-hydroxyglutarate dehydrogenase (L2HGDH)-mediated S-2HG catabolism in macrophages promotes tumor regression. Mechanistically, based on its structural similarity to α-ketoglutarate (α-KG), S-2HG has the potential to block the enzymatic activity of 2-oxoglutarate-dependent dioxygenases (2-OGDDs), consequently reshaping chromatin accessibility. Moreover, S-2HG-treated macrophages enhance CD8 T cell-mediated antitumor activity and sensitivity to anti-PD-1 therapy. Overall, our study uncovers the role of blockage of L2HGDH-mediated S-2HG catabolism in orchestrating macrophage antitumoral polarization and, further, provides the potential of repolarizing macrophages by S-2HG to overcome resistance to anti-PD-1 therapy.
Topics: Animals; Mice; Macrophages; Humans; Glutarates; Mice, Inbred C57BL; Cell Line, Tumor; Tumor Microenvironment; Cell Polarity; Alcohol Oxidoreductases; Tumor-Associated Macrophages; CD8-Positive T-Lymphocytes; Macrophage Activation; Neoplasms; Female
PubMed: 38829739
DOI: 10.1016/j.celrep.2024.114300