Parkinson’s disease (PD) is characterized by degeneration of nigrostriatal dopaminergic (DA) neurons. Mice treated with MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) exhibit microglial ...activation-induced oxidative stress and inflammation, and nigrostriatal DA neuronal damage, and thus serve as an experimental model of PD. Here, we report that fluoxetine, one of the most commonly prescribed antidepressants, prevents MPTP-induced degeneration of nigrostriatal DA neurons and increases striatal dopamine levels with the partial motor recovery. This was accompanied by inhibiting transient expression of proinflammatory cytokines and inducible nitric oxide synthase; and attenuating microglial NADPH oxidase activation, reactive oxygen species/reactive nitrogen species production, and consequent oxidative damage. Interestingly, fluoxetine was found to protect DA neuronal damage from 1-methyl-4-phenyl-pyridinium (MPP
+) neurotoxicity in co-cultures of mesencephalic neurons and microglia but not in neuron-enriched mesencephalic cultures devoid of microglia. The present in vivo and in vitro findings show that fluoxetine may possess anti-inflammatory properties and inhibit glial activation-mediated oxidative stress. Therefore, we carefully propose that neuroprotection of fluoxetine might be associated with its anti-inflammatory properties and could be employed as novel therapeutic agents for PD and other disorders associated with neuroinflammation and microglia-derived oxidative damage.
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► Fluoxetine rescues nigrostriatal DA neurons from MPTP neurotoxicity. ► Fluoxetine improves MPTP-induced behavior dysfunction. ► Fluoxetine inhibits microglial activation-mediated oxidative stress. ► Fluoxetine possesses anti-inflammatory properties.
Computed tomography (CT) imaging has been widely used for the diagnosis and surveillance of diseases. Although CT is attracting attention due to its reasonable price, short scan time, and excellent ...diagnostic ability, there are severe drawbacks of conventional CT contrast agents, such as low sensitivity, serious toxicity, and complicated synthesis process. Herein, we describe iodine-doped carbon dots (IDC) for enhancing the abilities of CT contrast agents. IDC was synthesized by one-pot hydrothermal synthesis for 4 h at 180 â and analysis of its structure and size distribution with UV-Vis, XPS, FT-IR, NMR, TEM, and DLS. Furthermore, the CT values of IDC were calculated and compared with those of conventional CT contrast agents (Iohexol), and the in vitro and in vivo toxicities of IDC were determined to prove their safety. IDC showed improved CT contrast enhancement compared to iohexol. The biocompatibility of the IDC was verified via cytotoxicity tests, hemolysis assays, chemical analysis, and histological analysis. The osmotic pressure of IDC was lower than that of iohexol, resulting in no dilution-induced contrast decrease in plasma. Based on these results, the remarkable CT contrast enhancement and biocompatibility of IDC can be used as an effective CT contrast agent for the diagnosis of various diseases compared with conventional CT contrast agents.
Currently there is no neuroprotective or neurorestorative therapy for Parkinson's disease. Here we report that transient receptor potential vanilloid 1 (TRPV1) on astrocytes mediates endogenous ...production of ciliary neurotrophic factor (CNTF), which prevents the active degeneration of dopamine neurons and leads to behavioural recovery through CNTF receptor alpha (CNTFRα) on nigral dopamine neurons in both the MPP(+)-lesioned or adeno-associated virus α-synuclein rat models of Parkinson's disease. Western blot and immunohistochemical analysis of human post-mortem substantia nigra from Parkinson's disease suggests that this endogenous neuroprotective system (TRPV1 and CNTF on astrocytes, and CNTFRα on dopamine neurons) might have relevance to human Parkinson's disease. Our results suggest that activation of astrocytic TRPV1 activates endogenous neuroprotective machinery in vivo and that it is a novel therapeutic target for the treatment of Parkinson's disease.
Adenocarcinosarcoma,a neoplasm containing both carcinomatous and sarcomatous components,is a rare form of a cancer and the pathophysiology is currently poorly understood.Moreover,definitive treatment ...guidelines for this disease have not yet been established.Pancreatic adenocarcinosarcoma is even more rare and the prognosis is fatal.Here,we report a case of a 77-year-old male with pancreatic adenocarcinosarcoma and metastasis to the liver.The patient presented at our hospital with uncontrolled glucose levels and diabetes mellitus.The patient’s laboratory findings were unremarkable with the exception of elevated carbohydrate antigen 19-9 levels.Biopsies of the tumors in the pancreas and the liver revealed two types of tumors:pancreatic adenocarcinoma and a poorly differentiated sarcoma.To determine if KRAS mutations were present,we performed a peptide nucleic acid(PNA) clamp PCR-based assay.DNA sequencing by PNA clamp PCR identified a point mutation in codon 12 of exon 2 within KRAS from both tumor types.Because the KRAS mutation is observed in both tumor components,our findings support a monoclonal tumor origin followed by subsequent divergent differentiation into the sarcomatous and carcinomatous tumor populations.After we considered the patient’s status and the late stage of tumor detection,gemcitabine chemotherapy was administered.
We propose new fabrication methods of a pixel-isolated liquid crystal (LC) structure for flexible display applications. In the LC structure fabricated through the proposed method, the patterned ...interpixel walls for sustaining the cell thickness are supported by the solidified polymer layer through anisotropic phase separation of LC/polymer composite, causing the alignment of the LC molecules to have very good mechanical stability against external pressure. In addition, we show that such pixel-isolating walls can be made by the stamping method which can be applied to fabricate large size plastic LCDs by roll-to-roll processing.
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•The issues and demands for MOF commercialization are discussed.•Scalable MOF synthesis, recovery, drying, and post-processing processes are discussed.•Future applications that have ...significant potential for MOF commercialization are investigated.
Progress in metal–organic frameworks (MOFs) has advanced from fundamental chemistry to engineering processes and applications, resulting in new industrial opportunities. The unique features of MOFs, such as their permanent porosity, high surface area, and structural flexibility, continue to draw industrial interest outside the traditional MOF field, both to solve existing challenges and to create new businesses. In this context, diverse research has been directed toward commercializing MOFs, but such studies have been performed according to a variety of individual goals. Therefore, there have been limited opportunities to share the challenges, goals, and findings with most of the MOF field. In this review, we examine the issues and demands for MOF commercialization and investigate recent advances in MOF process engineering and applications. Specifically, we discuss the criteria for MOF commercialization from the views of stability, producibility, regulations, and production cost. This review covers progress in the mass production and formation of MOFs along with future applications that are not currently well known but have high potential for new areas of MOF commercialization.
Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce cardiovascular events in humans with type 2 diabetes (T2D); however, the underlying mechanism remains unclear. Activation of the NLR family, ...pyrin domain-containing 3 (NLRP3) inflammasome and subsequent interleukin (IL)-1β release induces atherosclerosis and heart failure. Here we show the effect of SGLT2 inhibitor empagliflozin on NLRP3 inflammasome activity. Patients with T2D and high cardiovascular risk receive SGLT2 inhibitor or sulfonylurea for 30 days, with NLRP3 inflammasome activation analyzed in macrophages. While the SGLT2 inhibitor's glucose-lowering capacity is similar to sulfonylurea, it shows a greater reduction in IL-1β secretion compared to sulfonylurea accompanied by increased serum β-hydroxybutyrate (BHB) and decreased serum insulin. Ex vivo experiments with macrophages verify the inhibitory effects of high BHB and low insulin levels on NLRP3 inflammasome activation. In conclusion, SGLT2 inhibitor attenuates NLRP3 inflammasome activation, which might help to explain its cardioprotective effects.
Assembling high-quality microbial genomes using only cost-effective Nanopore long-read systems such as Flongle is important to accelerate research on the microbial genome and the most critical point ...for this is the polishing process. In this study, we performed an evaluation based on BUSCO and Prokka gene prediction in terms of microbial genome assembly for eight state-of-the-art Nanopore polishing tools and combinations available. In the evaluation of individual tools, Homopolish, PEPPER, and Medaka demonstrated better results than others. In combination polishing, the second round Homopolish, and the PEPPER × medaka combination also showed better results than others. However, individual tools and combinations have specific limitations on usage and results. Depending on the target organism and the purpose of the downstream research, it is confirmed that there remain some difficulties in perfectly replacing the hybrid polishing carried out by the addition of a short-read. Nevertheless, through continuous improvement of the protein pores, related base-calling algorithms, and polishing tools based on improved error models, a high-quality microbial genome can be achieved using only Nanopore reads without the production of additional short-read data. The polishing strategy proposed in this study is expected to provide useful information for assembling the microbial genome using only Nanopore reads depending on the target microorganism and the purpose of the research.
Industrial development has led to the widespread production of toxic materials, including carcinogenic, mutagenic, and toxic chemicals. Even with strict management and control measures, such ...materials still pose threats to human health. Therefore, convenient chemical sensors are required for toxic chemical monitoring, such as optical, electrochemical, nanomaterial-based, and biological-system-based sensors. Many existing and new chemical sensors have been developed, as well as new methods based on novel technologies for detecting toxic materials. The emergence of material sciences and advanced technologies for fabrication and signal-transducing processes has led to substantial improvements in the sensing elements for target recognition and signal-transducing elements for reporting interactions between targets and sensing elements. Many excellent reviews have effectively summarized the general principles and applications of different types of chemical sensors. Therefore, this review focuses on chemical sensor advancements in terms of the sensing and signal-transducing elements, as well as more recent achievements in chemical sensors for toxic material detection. We also discuss recent trends in biosensors for the detection of toxic materials.
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