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1.
Angew Chem Int Ed Engl ; 63(12): e202315849, 2024 Mar 18.
Article in English | MEDLINE | ID: mdl-38155097

ABSTRACT

Polymerization-induced self-assembly (PISA) combines polymerization and in situ self-assembly of block copolymers in one system and has become a widely used method to prepare block copolymer nanoparticles at high concentrations. The persistence of polymers in the environment poses a huge threat to the ecosystem and represents a significant waste of resources. There is an urgent need to develop novel chemical approaches to synthesize degradable polymers. To meet with this demand, it is crucial to install degradability into PISA nanoparticles. Most recently, degradable PISA nanoparticles have been synthesized by introducing degradation mechanisms into either shell-forming or core-forming blocks. This Minireview summarizes the development in degradable block copolymer nanoparticles synthesized by PISA, including shell-degradable, core-degradable, and all-degradable nanoparticles. Future development will benefit from expansion of polymerization techniques with new degradation mechanisms and adaptation of high-throughput approaches for both PISA syntheses and degradation studies.

2.
Int J Mol Sci ; 24(3)2023 Feb 01.
Article in English | MEDLINE | ID: mdl-36769118

ABSTRACT

Poly(ethylene terephthalate) (PET) is a manufactured plastic broadly available, whereas improper disposal of PET waste has become a serious burden on the environment. Leaf-branch compost cutinase (LCC) is one of the most powerful and promising PET hydrolases, and its mutant LCCICCG shows high catalytic activity and excellent thermal stability. However, low binding affinity with PET has been found to dramatically limit its further industrial application. Herein, TrCBM and CfCBM were rationally selected from the CAZy database to construct fusion proteins with LCCICCG, and mechanistic studies revealed that these two domains could bind with PET favorably via polar amino acids. The optimal temperatures of LCCICCG-TrCBM and CfCBM-LCCICCG were measured to be 70 and 80 °C, respectively. Moreover, these two fusion proteins exhibited favorable thermal stability, maintaining 53.1% and 48.8% of initial activity after the incubation at 90 °C for 300 min. Compared with LCCICCG, the binding affinity of LCCICCG-TrCBM and CfCBM-LCCICCG for PET has been improved by 1.4- and 1.3-fold, respectively, and meanwhile their degradation efficiency on PET films was enhanced by 3.7% and 24.2%. Overall, this study demonstrated that the strategy of constructing fusion proteins is practical and prospective to facilitate the enzymatic PET degradation ability.


Subject(s)
Composting , Polyethylene Terephthalates , Polyethylene Terephthalates/chemistry , Prospective Studies , Carbohydrates
3.
Molecules ; 28(6)2023 Mar 20.
Article in English | MEDLINE | ID: mdl-36985786

ABSTRACT

The fruit of Rosa laevigata Michx. (FR), a traditional Chinese herb utilized for the treatment of a variety diseases, has notably diverse pharmacological activities including hepatoprotective, anti-oxidant, and anti-inflammatory effects. Despite ongoing research on illustrating the underlying anti-inflammatory mechanism of FR, the principal mechanism remained inadequately understood. In this study, we investigated in depth the molecular mechanism of the anti-inflammatory actions of the ethanol extract of FR (EFR) and its potential targets using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages in vitro. We showed that EFR effectively ameliorated the overproduction of inflammatory mediators and cytokines, as well as the expression of related genes. It was further demonstrated that LPS-induced activation of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) were significantly inhibited by pretreatment with EFR, accompanied by a concomitant decrease in the nuclear translocation of the p65 subunit of NF-κB and activator protein 1 (AP-1). In addition, EFR pretreatment potently prevented LPS-induced decreased phosphorylation of adenosine monophosphate-activated protein kinase (AMPK). Our data also revealed that the activation of AMPK and subsequent inhibition of the mammalian target of the rapamycin (mTOR) signaling pathway was probably responsible for the inhibitory effect of EFR on LPS-induced inflammatory responses, evidenced by reverse changes observed under the condition of AMPK inactivation following co-treatment with the AMPK-specific inhibitor Compound C. Finally, the main components with an anti-inflammatory effect in EFR were identified as madecassic acid, ellagic acid, quinic acid, and procyanidin C1 by LC-MS and testified based on the inhibition of NO production and inflammatory mediator expression. Taken together, our results indicated that EFR was able to ameliorate inflammatory responses via the suppression of MAPKs/NF-κB signaling pathways following AMPK activation, suggesting the therapeutic potential of EFR for inflammatory diseases.


Subject(s)
NF-kappa B , Rosa , Animals , Mice , NF-kappa B/metabolism , AMP-Activated Protein Kinases/metabolism , Rosa/metabolism , Lipopolysaccharides/pharmacology , Fruit/metabolism , Macrophages , Signal Transduction , Anti-Inflammatory Agents/therapeutic use , RAW 264.7 Cells , Nitric Oxide/metabolism , Mammals/metabolism
4.
Angew Chem Int Ed Engl ; 61(46): e202213396, 2022 11 14.
Article in English | MEDLINE | ID: mdl-36151058

ABSTRACT

High-throughput synthesis of well-defined, ultrahigh molecular weight (UHMW) polymers by green approaches is highly desirable but remains unexplored. We report the creation of an atom-economic enzymatic cascade catalysis, consisting of formate oxidase (FOx) and horseradish peroxidase (HRP), that enables high-throughput reversible addition-fragmentation chain transfer (RAFT) synthesis of UHMW polymers at volumes down to 50 µL. FOx transforms formic acid, a C1 substrate, and oxygen to CO2 and H2 O2 , respectively. CO2 can escape from solution while H2 O2 is harnessed in situ by HRP to generate radicals from acetylacetone for RAFT polymerization, leaving no waste accumulation in solution. Oxygen-tolerant RAFT polymerization using enzymatic cascade redox cycles was successfully performed in vials and 96-well plates to produce libraries of well-defined UHMW polymers, and represents the first example of high-throughput synthesis method of such materials at extremely low volumes.


Subject(s)
Carbon Dioxide , Polymers , Polymers/chemistry , Molecular Weight , Polymerization , Catalysis , Horseradish Peroxidase , Oxygen
5.
Int Heart J ; 62(3): 607-615, 2021.
Article in English | MEDLINE | ID: mdl-34054001

ABSTRACT

The aim was to investigate the role of the α7nAChR-mediated cholinergic anti-inflammatory pathway in vagal nerve regulated atrial fibrillation (AF).18 beagles (standard dogs for testing) were used in this study, and the effective refractory period (ERP) of atrium and pulmonary veins and AF inducibility were measured hourly during rapid atrial pacing at 800 beats/minute for 6 hours in all beagles. After cessation of 3 hours of RAP, the low-level vagal nerve stimulation (LL-VNS) group (n = 6) was given LL-VNS and injection of salinne (0.5 mL/GP) into four GPs, the methyllycaconitine (MLA, the antagonist of α7nAChR) group (n = 6) was given LL-VNS and injection of MLA into four GPs, and the Control group (n = 6) was given saline into four GPs and the right cervical vagal nerve was exposed without stimulation. Then, the levels of the tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), acetylcholine (ACh), STAT3, and NF-κB proteins were measured. During the first 3 hours of RAP, the ERPs gradually decreased while the dispersion of ERPs (dERPs) and AF inducibility gradually increased in all three groups. During the last 3 hours of 6 hours' RAP in this study, the ERPs in the LL-VNS group were higher, while the dERPs and AF inducibility were significantly lower when compared with the Control and MLA groups at the same time points. The levels of ACh in the serum and atrium in the LL-VNS and MLA groups were higher than in the Control group, and the levels of TNF-α and IL-6 were higher in the Control and MLA groups than in the LL-VNS group. The concentrations of STAT3 in RA and LA tissues were higher in the LL-VNS group while those of NF-κB were lower.In conclusion, the cholinergic anti-inflammatory pathway mediated by α7nACh plays an important role in low-level vagal nerve-regulated AF.


Subject(s)
Aconitine/analogs & derivatives , Atrial Fibrillation/physiopathology , Neuroimmunomodulation/drug effects , Vagus Nerve/drug effects , alpha7 Nicotinic Acetylcholine Receptor/antagonists & inhibitors , Acetylcholine/blood , Aconitine/administration & dosage , Aconitine/pharmacology , Animals , Cardiac Pacing, Artificial/adverse effects , Cardiac Pacing, Artificial/methods , Case-Control Studies , Disease Models, Animal , Dogs , Heart Atria/innervation , Heart Atria/physiopathology , Interleukin-6/blood , NF-kappa B/blood , Nicotinic Antagonists/administration & dosage , Nicotinic Antagonists/pharmacology , Pulmonary Veins/innervation , Pulmonary Veins/physiopathology , Refractory Period, Electrophysiological/drug effects , STAT3 Transcription Factor/blood , Tumor Necrosis Factor-alpha/blood , Vagus Nerve Stimulation/adverse effects , Vagus Nerve Stimulation/methods
6.
Org Biomol Chem ; 16(4): 531-535, 2018 01 24.
Article in English | MEDLINE | ID: mdl-29303205

ABSTRACT

By using a transfer hydrogenative coupling strategy, we herein describe a new method for the efficient synthesis of anthranilic acid derivatives, a significantly important class of compounds with extensive applications in organic synthesis and the discovery of bioactive molecules, from 2-nitroaryl methanols and readily available alcohols/amines. The synthesis proceeds with the merits of no need for a transition metal catalyst, operational simplicity, broad substrate scope, good functional tolerance, and high step efficiency, which offers a useful alternative to access anthranilic acid derivatives.

7.
Europace ; 20(4): 712-718, 2018 04 01.
Article in English | MEDLINE | ID: mdl-28379329

ABSTRACT

Aims: Studies have shown that stellate ganglion nerve activity has association with atrial electrical remodelling and atrial fibrillation (AF) inducibility, while median nerve stimulation (MNS) decreases cardiac sympathetic drive. In this study, we tested the hypothesis that MNS suppresses atrial electrical remodelling and AF vulnerability. Methods and results: The atrial effective refractory period (AERP) and AF inducibility at baseline and after 3 h of rapid atrial pacing were determined in dogs undergoing MNS (n = 7), MNS+ application of methyllycaconitine (n = 7) or sham procedure (n = 6). Then, the levels of tumour necrosis factor-alpha (TNF-a), interleukin-6 (IL-6), and acetylcholine (Ach) in the plasma and atrial tissues were measured. The control dogs (n = 4) were assigned to measure atrial inflammation cytokines. Short-term rapid atrial pacing induced shortening of the AERP, an increase in AERP dispersion, and an increase AF vulnerability in the sham dogs, which were all suppressed by MNS. Levels of TNF-a and IL-6 were higher, and Ach levels were lower in the left and the right atrium in the sham dogs than in the MNS dogs. Methyllycaconitine blunted the effects of MNS on the AERP, AERP dispersion, the AF vulnerability, and TNF-a and IL-6 levels in the atrium, but had no impact on the levels of Ach. Conclusions: The effects of MNS on atrial electrical remodelling and AF inducibility might be associated with the cholinergic anti-inflammatory pathway.


Subject(s)
Atrial Fibrillation/therapy , Atrial Remodeling , Autonomic Nervous System/physiopathology , Cardiac Pacing, Artificial , Electric Stimulation Therapy/methods , Heart Atria/innervation , Heart Rate , Inflammation Mediators/blood , Median Nerve , Acetylcholine/blood , Action Potentials , Animals , Atrial Fibrillation/blood , Atrial Fibrillation/etiology , Atrial Fibrillation/physiopathology , Autonomic Nervous System/metabolism , Disease Models, Animal , Dogs , Interleukin-6/blood , Refractory Period, Electrophysiological , Tumor Necrosis Factor-alpha/blood
8.
Guang Pu Xue Yu Guang Pu Fen Xi ; 35(9): 2444-9, 2015 Sep.
Article in Zh | MEDLINE | ID: mdl-26669145

ABSTRACT

An in-house-built femtosecond laser ionization time-of-flight mass spectrometry (fs-LI-TOFMS) has been applied to the multi-elemental analysis of porcelain glaze from Yaozhou kiln. The samples are selected representing products of different dynasties, including Tang, Five, Song, Jin, and Ming Dynasty. For exploring the colorative mechanism of Yaozhou porcelain through the elemental analysis of the glaze, the effects of all potential coloring elements, especially transition elements, were considered. There was a speculation that the typical Co-Cr-Fe-Mn recipe was used in the fabrication of Yaozhou black glaze; the low content of Fe and high content of Ni resulted in the porcelain of white glaze; an increase content of P could lead the porcelain to be yellow-glazed. Undoubtedly, this research is an important supplement to the study of the colorative mechanism of the Yaozhou porcelain system.

9.
Spectrochim Acta A Mol Biomol Spectrosc ; 317: 124396, 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-38733911

ABSTRACT

Accurate prediction of the concentration of a large number of hyaluronic acid (HA) samples under temperature perturbations can facilitate the rapid determination of HA's appropriate applications. Near-infrared (NIR) spectroscopy analysis combined with deep learning presents an effective solution to this challenge, with current research in this area being scarce. Initially, we introduced a novel feature fusion method based on an intersection strategy and used two-dimensional correlation spectroscopy (2DCOS) and Aquaphotomics to interpret the interaction information in HA solutions reflected by the fused features. Subsequently, we created an innovative, multi-strategy improved Walrus Optimization Algorithm (MIWaOA) for parameter optimization of the deep extreme learning machine (DELM). The final constructed MIWaOA-DELM model demonstrated superior performance compared to partial least squares (PLS), extreme learning machine (ELM), DELM, and WaOA-DELM models. The results of this study can provide a reference for the quantitative analysis of biomacromolecules in complex systems.

10.
Se Pu ; 41(1): 76-86, 2023 Jan.
Article in Zh | MEDLINE | ID: mdl-36633079

ABSTRACT

With the increasing number of cosmetic products, their flavor and fragrance components are receiving greater and greater attention. Establishing an analytical method of determining these components in cosmetics is one of the most effective measures to eliminate consumers' concerns. In this study, a method for the simultaneous determination of 28 fragrance residues in cosmetics by gas chromatography-tandem mass spectrometry (GC-MS/MS) was developed. The samples were extracted using methanol and those containing more oil and grease were purified using a neutral alumina solid-phase extraction column, whereas those with more complex compositions were purified by QuEChERS. The analytes in the samples were measured by GC-MS/MS, characterized using their retention times and characteristic ion pairs, and quantified with an external standard. The respective limits of detection (LODs, S/N=3) and quantification (LOQs, S/N>10) of the compounds were in the ranges 2-20 and 5-50 µg/kg. The linearities of the concentration curves of the 28 substances were good in the ranges 1-100, 2-200, 4-200, and 10-1000 µg/L, and the correlation coefficients of the quantitative ion pairs were >0.999. Twenty-eight fragrances were added to blank samples at spiked levels of 50-500 µg/kg, and the recoveries ranged from 71.3% to 120.4%, with RSDs of 1.5%-14.6%. The method could be applied in the determination of fragrances in cosmetics because it was simple, sensitive, and stable and could effectively exclude the interferences of complex matrices. The method was used to determine the fragrance components in 16 cosmetic products, and some fragrance components were detected in 12 samples. Increased attention should be paid to the safeties of fragrances and flavors used in cosmetics.


Subject(s)
Cosmetics , Perfume , Tandem Mass Spectrometry , Odorants/analysis , Gas Chromatography-Mass Spectrometry , Cosmetics/analysis , Perfume/analysis , Solid Phase Extraction , Chromatography, High Pressure Liquid
11.
Front Microbiol ; 14: 1172257, 2023.
Article in English | MEDLINE | ID: mdl-37389349

ABSTRACT

Introduction: Invasive fungal infections (IFIs) are fatally threatening to critical patients. The fungal defensin as an antifungal protein can widely inhibit fungi. Methods: In this study, eight antifungal genes from different filamentous fungi were optimized by synonymous codon bias and heterologously expressed in Escherichia coli. Results and discussion: Only the antifungal protein (AFP) from Aspergillus giganteus was produced, whereas the AFP from its mutation of the chitin-binding domain could not be expressed, thereby suggesting the importance of the motif for protein folding. In addition, the recombinant AFP (rAFP, 100 µg/mL) pre-heated at 50°C for 1 h effectively inhibited Paecilomyces variotii CICC40716 of IFIs by 55%, and no cell cytotoxicity was observed in RAW264.7 cells. After being pre-heated at 50°C for 8 h, the fluorescence emission intensity of the rAFP decreased and shifted from 343 nm to 335 nm. Moreover, the helix and ß-turn of the rAFP gradually decreased with the pre-heated treatment temperature of 50°C via circular dichroism spectroscopy. Propidium iodide staining revealed that the rAFP could cause damage to the cell membrane. Moreover, the corresponding differentially expressed genes (DEGs) for downregulation such as amino sugar and nucleotide sugar metabolism, as well as mitogen-activated protein kinase (MAPK) signaling pathway involved in the cell wall integrity were found via the RNA-seq of rAFP treatment. By contrast, the upregulated DEGs were enriched in response to the oxidative stress of Biological Process by the Gene Ontology (GO) database. The encoding proteins of laccase, multicopper oxidase, and nitroreductase that contributed to reactive oxygen species (ROS) scavenging could be recognized. These results suggested that the rAFP may affect the integrity of the cell wall and cell membrane, and promote the increase in ROS, thereby resulting in fungal death. Consequently, drug development could be based on the inhibitory effect of the rAFP on IFIs.

12.
BMC Complement Med Ther ; 23(1): 286, 2023 Aug 14.
Article in English | MEDLINE | ID: mdl-37580785

ABSTRACT

BACKGROUND: Tea (Camellia sinensis L.) flowers will compete with tea leaves in nutrition and are abandoned as an undesirable by-product. In this study, the biological efficacy of tea flowers was investigated. Further exploration of its antifungal activity was explained. METHODS: Tea flowers harvested from China were characterized in term of component, antioxidant ability, tyrosinase inhibition, and antifungal ability. Chemical compounds of tea flowers were analyzed by LC-MS. Disinfectant compounds were identified in tea flowers, and 2-ketobutyric acid exhibited antifungal activity against Aspergillus flavusCCTCC AF 2023038. The antifungal mechanism of 2-ketobutyric acid was further investigated by RNA-seq. RESULTS: Water-soluble tea flower extracts (TFEs) exhibited free radical scavenging activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2, 2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS) as well as a high ferric-reducing ability. However, no inhibition of tyrosinase activity was observed. In the antifungal test, 6.4 mg/mL TFE reached 71.5% antifungal rate and the electrical conductivity of the culture broth increased with increasing concentration of TFE, implying that it damaged the fungal cell membrane by the TFE. Several disinfectants were identified in TFE by LC-MS, and 2-ketobutyric acid was also confirmed to be capable of fungal inhibition. Propidium iodide (PI) staining indicated that 2-ketobutyric acid caused damage to the cell membrane. RNA-seq analysis revealed that 3,808 differentially expressed genes (DEGs) were found in A. flavus CCTCC AF 2023038 treated by 2-ketobutyric acid, and more than 1,000 DEGs involved in the integral and intrinsic component of membrane were affected. Moreover, 2-ketobutyric acid downregulated aflatoxin biosynthesis genes and decreased the aflatoxin production. CONCLUSIONS: Overall, TFE exhibited excellent antioxidant ability and fungal inhibition against A. flavus CCTCC AF 2023038 due to its abundant disinfectant compounds. As a recognized food additive, 2-ketobutyric acid is safe to use in the food industry and can be utilized as the basis for the research and development of strong fungicides.


Subject(s)
Camellia sinensis , Flowers , Plant Extracts , Antifungal Agents/pharmacology , Aspergillus flavus/drug effects , Camellia sinensis/chemistry , Flowers/chemistry , Plant Extracts/pharmacology
13.
Front Oncol ; 13: 1064548, 2023.
Article in English | MEDLINE | ID: mdl-37168370

ABSTRACT

Three-dimensional cell tissue culture, which produces biological structures termed organoids, has rapidly promoted the progress of biological research, including basic research, drug discovery, and regenerative medicine. However, due to the lack of algorithms and software, analysis of organoid growth is labor intensive and time-consuming. Currently it requires individual measurements using software such as ImageJ, leading to low screening efficiency when used for a high throughput screen. To solve this problem, we developed a bladder cancer organoid culture system, generated microscopic images, and developed a novel automatic image segmentation model, AU2Net (Attention and Cross U2Net). Using a dataset of two hundred images from growing organoids (day1 to day 7) and organoids with or without drug treatment, our model applies deep learning technology for image segmentation. To further improve the accuracy of model prediction, a variety of methods are integrated to improve the model's specificity, including adding Grouping Cross Merge (GCM) modules at the model's jump joints to strengthen the model's feature information. After feature information acquisition, a residual attentional gate (RAG) is added to suppress unnecessary feature propagation and improve the precision of organoids segmentation by establishing rich context-dependent models for local features. Experimental results show that each optimization scheme can significantly improve model performance. The sensitivity, specificity, and F1-Score of the ACU2Net model reached 94.81%, 88.50%, and 91.54% respectively, which exceed those of U-Net, Attention U-Net, and other available network models. Together, this novel ACU2Net model can provide more accurate segmentation results from organoid images and can improve the efficiency of drug screening evaluation using organoids.

14.
Sheng Wu Gong Cheng Xue Bao ; 38(6): 2292-2307, 2022 Jun 25.
Article in Zh | MEDLINE | ID: mdl-35786480

ABSTRACT

Proteolytic enzymes and lipopeptides contain broad-spectrum antimicrobial activities, which have great potential for research and development. A microbial strain X49 obtained from protease screening plate showed antifungal activities against six fungi. Biochemical analysis, 16S rRNA sequencing, API identification system, and electron microscope analysis were carried out to identify the bacterium. Azocasein method was used to analyze the protease activity. Lipopeptides were extracted for antifungal analysis. The result indicated that strain X49 grew in the range of 10-50 ℃ and pH 4.0-9.0. Moreover, it survived in 10% NaCl, showing good halotolerance. Strain X49 was identified as Bacillus velezensis. Genomic analysis of B. velezensis X49 revealed eleven genes encoding serine protease. The ID 1_894 belonging to S8 subtilisin family was 99% similar to the serine protease with known antifungal ability. On the other hand, thirty genes encoding non-ribosomal peptide synthetase involved in the lipopeptide biosynthesis, including surfactin, iturin, fengycin, bacitracin, and gramicidin, were identified. Part of the extracellular proteolytic activity remained under high temperature. After co-fermentation of B. velezensis X49 with Zingiber officinale Rosc., the antifungal activity of the lipopeptide extract from the co-fermentation was greatly improved. In conclusion, B. velezensis X49 showed clear inhibitory effect on both plant and human pathogens. The active substances co-fermented with Chinese herbs and microbes can be utilized for further drug development.


Subject(s)
Antifungal Agents , Genomics , Antifungal Agents/pharmacology , Bacillus , Humans , Lipopeptides/genetics , Lipopeptides/pharmacology , RNA, Ribosomal, 16S , Serine Proteases
15.
Front Pharmacol ; 13: 1080273, 2022.
Article in English | MEDLINE | ID: mdl-36588731

ABSTRACT

Organoids are self-organized three-dimensional in vitro cell cultures derived from stem cells. They can recapitulate organ development, tissue regeneration, and disease progression and, hence, have broad applications in drug discovery. However, the lack of effective graphic algorithms for organoid growth analysis has slowed the development of organoid-based drug screening. In this study, we take advantage of a bladder cancer organoid system and develop a deep learning model, the res-double dynamic conv attention U-Net (RDAU-Net) model, to improve the efficiency and accuracy of organoid-based drug screenings. In this RDAU-Net model, the dynamic convolution and attention modules are integrated. The feature-extracting capability of the encoder and the utilization of multi-scale information are substantially enhanced, and the semantic gap caused by skip connections has been filled, which substantially improved its anti-interference ability. A total of 200 images of bladder cancer organoids on culture days 1, 3, 5, and 7, with or without drug treatment, were employed for training and testing. Compared with the other variations of the U-Net model, the segmentation indicators, such as Intersection over Union and dice similarity coefficient, in the RDAU-Net model have been improved. In addition, this algorithm effectively prevented false identification and missing identification, while maintaining a smooth edge contour of segmentation results. In summary, we proposed a novel method based on a deep learning model which could significantly improve the efficiency and accuracy of high-throughput drug screening and evaluation using organoids.

16.
Antioxidants (Basel) ; 11(12)2022 Nov 30.
Article in English | MEDLINE | ID: mdl-36552584

ABSTRACT

Cerebral ischemic stroke is characterized by acute ischemia in a certain part of the brain, which leads to brain cells necrosis, apoptosis, ferroptosis, pyroptosis, etc. At present, there are limited effective clinical treatments for cerebral ischemic stroke, and the recovery of cerebral blood circulation will lead to cerebral ischemia-reperfusion injury (CIRI). Cerebral ischemic stroke involves many pathological processes such as oxidative stress, inflammation, and mitochondrial dysfunction. Nuclear factor erythroid 2-related factor 2 (Nrf2), as one of the most critical antioxidant transcription factors in cells, can coordinate various cytoprotective factors to inhibit oxidative stress. Targeting Nrf2 is considered as a potential strategy to prevent and treat cerebral ischemia injury. During cerebral ischemia, Nrf2 participates in signaling pathways such as Keap1, PI3K/AKT, MAPK, NF-κB, and HO-1, and then alleviates cerebral ischemia injury or CIRI by inhibiting oxidative stress, anti-inflammation, maintaining mitochondrial homeostasis, protecting the blood-brain barrier, and inhibiting ferroptosis. In this review, we have discussed the structure of Nrf2, the mechanisms of Nrf2 in cerebral ischemic stroke, the related research on the treatment of cerebral ischemia through the Nrf2 signaling pathway in recent years, and expounded the important role and future potential of the Nrf2 pathway in cerebral ischemic stroke.

17.
Front Cell Neurosci ; 16: 864426, 2022.
Article in English | MEDLINE | ID: mdl-35602556

ABSTRACT

Ischemic stroke is an acute cerebrovascular disease characterized by sudden interruption of blood flow in a certain part of the brain, leading to serious disability and death. At present, treatment methods for ischemic stroke are limited to thrombolysis or thrombus removal, but the treatment window is very narrow. However, recovery of cerebral blood circulation further causes cerebral ischemia/reperfusion injury (CIRI). The endoplasmic reticulum (ER) plays an important role in protein secretion, membrane protein folding, transportation, and maintenance of intracellular calcium homeostasis. Endoplasmic reticulum stress (ERS) plays a crucial role in cerebral ischemia pathophysiology. Mild ERS helps improve cell tolerance and restore cell homeostasis; however, excessive or long-term ERS causes apoptotic pathway activation. Specifically, the protein kinase R-like endoplasmic reticulum kinase (PERK), activating transcription factor 6 (ATF6), and inositol-requiring enzyme 1 (IRE1) pathways are significantly activated following initiation of the unfolded protein response (UPR). CIRI-induced apoptosis leads to nerve cell death, which ultimately aggravates neurological deficits in patients. Therefore, it is necessary and important to comprehensively explore the mechanism of ERS in CIRI to identify methods for preserving brain cells and neuronal function after ischemia.

18.
J Hazard Mater ; 416: 125907, 2021 08 15.
Article in English | MEDLINE | ID: mdl-34492842

ABSTRACT

Polyacrylamide (PAM) is widely used in polymer flooding processes to increase oil recovery while the byproduct of PAM-containing wastewater is a serious environmental issue. In this study, electrochemical oxidation process (EAOP) was applied for treating PAM wastewater using a new type of 3-dimensional ultra-thin SnO2-Sb electrode. Nano-sized catalysts were evenly dispersed both on the surface and inside of a porous Ti filter forming nano-thickness catalytic layer that enhances the utilization and bonding of catalysts. This porous Ti electrode showed 20% improved OH· production and 16.3 times increased accelerated service life than the planar Ti electrode. Using this electrode to treat 100 mg L-1 PAM, the TOC removal efficiency reached over 99% within 3 h under current density of 20 mA cm-2. The EAOP could fastly break the long-chain PAM molecules into small molecular intermediates. With the porous electrode treating 5 g L-1 PAM under current density of 30 mA cm-2, EAOP reduced 94.2% of average molecular weight in 1 h and 92.0% of solution viscosity in 0.5 h. Moreover, the biodegradability of PAM solution was significantly improved as the solution BOD5/COD ratio raised from 0.05 to 0.41 after 4 h treatment. The degradation pathway of PAM was also investigated.


Subject(s)
Tin Compounds , Water Pollutants, Chemical , Acrylic Resins , Electrodes , Oxidation-Reduction , Titanium , Wastewater
19.
Front Integr Neurosci ; 15: 721833, 2021.
Article in English | MEDLINE | ID: mdl-35115912

ABSTRACT

Somatic symptom disorder (SSD) is a form of mental illness that causes one or more distressing somatic symptoms leading to a significant disruption to everyday life, characterized by excessive thoughts, feelings, or behaviors related to these symptoms. While SSD is characterized by significant discomfort in some parts of the body, these symptoms are not related to any known medical condition and therefore it cannot be diagnosed using any medical instrument examination. Currently available treatments for SSD, including drug therapy and psychotherapy (such as cognitive behavioral therapy), usually improve psychiatric symptoms, but the results are often disappointing. Furthermore, SSD is often comorbid with anxiety and depression (75.1 and 65.7%, respectively). Importantly, interventions targeting the anterior limb of the internal capsule (ALIC; e.g., deep brain stimulation and thermal ablation) can effectively treat various mental disorders, such as refractory obsessive-compulsive disorder, depression, and eating disorders, suggesting that it may also be effective for treating the depressive symptoms associated with SSD comorbidity. In this report, a 65-year-old woman diagnosed with SSD accompanied with depression and anxiety underwent bilateral anterior capsulotomy. The patient complained of nausea and vomiting, swelling of the hilum of the liver for 14 years, weakness of the limbs for 13 years, and burning pain in the esophagus for 1 year. Psychiatric and neuropsychological assessments were conducted to record the severity of the patients' symptoms and the progression of postoperative symptoms. The patient's somatization, depression, and anxiety symptoms as well as quality of life improved significantly and steadily; thus, anti-depressive and anti-anxiety medication were stopped. However, the patient developed new somatization symptoms, including dizziness, headache, and sternal pain, 10 months after the operation. Therefore, the patient resumed taking flupentixol and melitracen in order to control the new symptoms. This study shows that bilateral anterior capsulotomy appears to be a complementary treatment for refractory SSD with depressive and anxiety symptoms. Furthermore, postoperative use of anxiolytic and antidepressant medications may be useful for controlling future somatization symptoms.

20.
Europace ; 12(6): 805-10, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20353962

ABSTRACT

AIMS: The effects of ganglionated plexi (GP) ablation on atrial fibrillation (AF) inducibility and atrial autonomic innervation remodelling have not been elucidated. METHODS AND RESULTS: Thirteen dogs were randomly divided into sham-operated group and GP ablation group. All animals underwent a right thoracotomy at the fourth intercostal space. Atrial fibrillation inducibility was assessed by burst rapid pacing at right atrium (RA). After anterior right GP and inferior right GP ablation, AF inducibility was assessed in the GP ablation group. The animals were allowed to recover for 8 weeks, after which, AF was measured again. The levels of atrial natriuretic peptide (ANP) in blood and atrial tissues were examined by radioimmunoassay. Immunocytochemical staining of cardiac nerves was performed in tissues from the dogs. Atrial fibrillation was induced easily in the GP ablation group after 8 weeks although AF was not observed in the sham-operated group, and after instant GP ablation. Compared with that in the sham-operated group, the levels of ANP in the blood and RA increased significantly 8 weeks after GP ablation (111.4 +/- 18.2 vs. 175.1 +/- 25.9; 184.9 +/- 36.3 vs. 299.1 +/- 32.5; P < 0.05). In the GP ablation group, the density of growth-associated protein 43-positive, tyrosine hydroxylase-positive, and choline acetyltransferase-positive nerves in the RA was 821 +/- 752, 481 +/- 627, and 629 +/- 644 per mm(2), respectively, which was significantly (P < 0.01) lower than the nerve density in sham-operated tissues (2590 +/- 841, 1752 +/- 605, and 3147 +/- 886 per mm(2), respectively). CONCLUSION: Atrial autonomic innervations remodelling may be the mechanism of induced AF after GP ablation.


Subject(s)
Atrial Fibrillation/etiology , Atrial Fibrillation/physiopathology , Catheter Ablation , Ganglia, Autonomic/physiology , Heart/innervation , Animals , Atrial Fibrillation/diagnosis , Atrial Natriuretic Factor/blood , Autonomic Pathways/physiology , Autonomic Pathways/surgery , Cardiac Pacing, Artificial , Cardiac Volume , Cholinergic Fibers/metabolism , Denervation/methods , Disease Models, Animal , Dogs , Electrocardiography , Female , GAP-43 Protein/metabolism , Ganglia, Autonomic/surgery , Heart/physiopathology , Heart Atria/innervation , Heart Atria/physiopathology , Immunohistochemistry , Male , Radioimmunoassay , Recurrence
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