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1.
Adv Sci (Weinh) ; : e2401855, 2024 Jul 07.
Article in English | MEDLINE | ID: mdl-38973158

ABSTRACT

Clinically, chronic pain and depression often coexist in multiple diseases and reciprocally reinforce each other, which greatly escalates the difficulty of treatment. The neural circuit mechanism underlying the chronic pain/depression comorbidity remains unclear. The present study reports that two distinct subregions in the paraventricular thalamus (PVT) play different roles in this pathological process. In the first subregion PVT posterior (PVP), glutamatergic neurons (PVPGlu) send signals to GABAergic neurons (VLPAGGABA) in the ventrolateral periaqueductal gray (VLPAG), which mediates painful behavior in comorbidity. Meanwhile, in another subregion PVT anterior (PVA), glutamatergic neurons (PVAGlu) send signals to the nucleus accumbens D1-positive neurons and D2-positive neurons (NAcD1→D2), which is involved in depression-like behavior in comorbidity. This study demonstrates that the distinct thalamo-subcortical circuits PVPGlu→VLPAGGABA and PVAGlu→NAcD1→D2 mediated painful behavior and depression-like behavior following spared nerve injury (SNI), respectively, which provides the circuit-based potential targets for preventing and treating comorbidity.

2.
ACS Omega ; 9(26): 28666-28675, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38973902

ABSTRACT

Skeletal muscle ischemia-reperfusion (IR) injury is a prevalent type of muscle injury caused by events, such as trauma, arterial embolism, and primary thrombosis. The development of an IR injury is associated with oxidative stress and an excessive inflammatory response. Nanozymes, which have exceptional free radical scavenging activities, have gained significant attention for treating oxidative stress. This study demonstrates that carbon dot (C-dot) nanozymes possess superoxide dismutase (SOD)-like activity and can act as free radical scavengers. The carbon dot nanozymes are presented to mitigate inflammation by downregulating the iNOS/COX-2 pathway and scavenging reactive oxygen-nitrogen species to reduce oxidative stress, thereby suppressing inflammation. In the IR injury of skeletal muscle mice, we demonstrate that C-dots can effectively reduce inflammatory cytokines and tissue edema in skeletal muscle following IR injury in the limb. These findings suggest that C-dots have potential as a therapeutic approach for IR injury of skeletal muscle with negligible systemic toxicity. This offers a promising strategy for clinical intervention.

3.
Pharmacol Res ; 206: 107279, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38942340

ABSTRACT

Transfer RNA-derived small RNAs (tsRNAs) are a class of small non-coding RNA (sncRNA) molecules derived from tRNA, including tRNA derived fragments (tRFs) and tRNA halfs (tiRNAs). tsRNAs can affect cell functions by participating in gene expression regulation, translation regulation, intercellular signal transduction, and immune response. They have been shown to play an important role in various human diseases, including cardiovascular diseases (CVDs). Targeted regulation of tsRNAs expression can affect the progression of CVDs. The tsRNAs induced by pathological conditions can be detected when released into the extracellular, giving them enormous potential as disease biomarkers. Here, we review the biogenesis, degradation process and related functional mechanisms of tsRNAs, and discuss the research progress and application prospects of tsRNAs in different CVDs, to provide a new perspective on the treatment of CVDs.

4.
Poult Sci ; 103(8): 103887, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38861845

ABSTRACT

Hyperuricemia (HUA) is a metabolic disorder caused by excessive production of uric acid (UA) or impaired uric acid metabolism. Smilax China L. has a wide range of pharmacological activities such as immunomodulatory, anti-inflammatory, and antioxidant. Its roots and rhizomes have been widely used for the treatment of HUA. However, its mechanisms for treating HUA and reducing renal impairment have not been fully elucidated. In the present study, we evaluated the effect of Smilax China L. extract (SC) on UA metabolism and further explored its mechanism of action by feeding a high-calcium and high-protein diet to chickens to induce a model of HUA in chickens. SC significantly reduced serum UA levels and improved renal function in hyperuricemic chickens. Meanwhile, SC was able to inhibit the activity of xanthine oxidase (XOD) in vivo and in vitro, reducing the production of uric acid. In addition, SC was able to increase the expression of Breast Cancer Resistance Protein (BCRP) in the kidney and ileum and increase uric acid excretion. Therefore, our results suggest that SC may be a candidate for anti-hyperuricemia.

5.
Spectrochim Acta A Mol Biomol Spectrosc ; 321: 124685, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38909561

ABSTRACT

Nickel ion (Ni2+) and pH play an important role in environment and living organisms. A fluorescent probe "naphthalimide- s-triazine" (NCNS) for targeted dual detection of Ni2+ and pH was synthesized. As a result, NCNS exhibits excellent optical properties: a much larger Stokes shift (140 nm), eminent changes of fluorescence intensity and significant red-shift both for Ni2+ and pH. As for the detection of Ni2+, the selectivity is high and the anti-interference is strong. NCNS can fluorescently detect Ni2+ in a wider pH range from 4.0 to 10.5. It provides a much lower limit of detection (LOD, 20.03 nM), a rapid response time (150 s) and six times reversibility, showing the high sensitivity. Particularly, NCNS can be applied to fluorescently detect Ni2+ in actual water samples and HA-VSMC imaging. In the detection of pH, the probe generates a ratiometric fluorescence in a wide pH range (3.0 âˆ¼ 12.3). NCNS has been successfully made test paper both for Ni2+ and pH. The mechanisms of the double recognition are verified by the density functional theory (DFT) calculations and the nuclear magnetic resonance (NMR) titration experiments.

6.
Zhen Ci Yan Jiu ; 49(6): 585-593, 2024 Jun 25.
Article in English, Chinese | MEDLINE | ID: mdl-38897802

ABSTRACT

OBJECTIVES: To observe the effect of heat-reinforcing needling (HRN) on synovial inflammation, hypoxia-inducible factor-1α (HIF-1α) and glycolytic activity in serum and synovial tissue in rabbits with cold syndrome of rheumatoid arthritis (RA), so as to explore its mechanisms underlying improvement of RA. METHODS: A total of 32 rabbits were randomly divided into normal, model, inhibitor and HRN groups, with 8 rabbits in each group. The RA with cold syndrome model was induced by injecting ovalbumin dry powder and Freund's complete adjuvant combined with cold freezing. Rabbits in the inhibitor group were intraperitoneally injected with 2-methoxyestradiol (2.5 mg/kg), rabbits in the HRN group were received HRN at bilateral "Zusanli" (ST36) for 30 min. The treatments were conducted once daily for 14 consecutive days. After the interventions, the knee circumference and pain threshold were measured. The contents of nicotinamide adenine dinucleotide phosphoric (NADPH), Hexokinase II (HK2) and 6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase 3 (PFKFB3) in serum of rabbits were detected by ELISA. The pathological morphology of synovial tissue of the knee joints were observed by HE staining. The positive expressions of tumor necrosis factor (TNF-α), interleukin (IL)-1ß, IL-6 and IL-17 in synovial tissue of knee joint were detected by immunohistochemistry. The content of lactic acid in synovial tissue of rabbit knee joint was detected by spectrophotometry. The expression levels of HIF-1α, pyruvate kinase 2 (PKM2) and lactate dehydrogenase (LDHA) in synovial tissue of knee joint were detected by Western blot. RESULTS: After intervention, compared with the normal group, the knee circumference was significantly enlarged (P<0.05), the pain threshold was significantly decreased (P<0.05);the synovial tissue of knee joints showed significant cell proliferation and inflammatory infiltration, the pathological score was significantly increased (P<0.05);positive expressions of TNF-α, IL-1ß, IL-6 and IL-17, the content of lactic acid in synovial tissue, the contents of NADPH, HK2 and PFKFB3 in serum, and the protein expression levels of HIF-1α, PKM2 and LDHA in synovial tissue were increased (all P<0.05) in the model group. Compared with model group, the circumference of knee joint was significantly decreased (P<0.05), the pain threshold was significantly increased (P<0.05);in synovial tissue, the pathological score was decreased (P<0.05);the positive expressions of TNF-α, IL-1ß, IL-6 and IL-17 in synovial tissue were decreased (P<0.05), the lactic acid content in synovial tissue was decreased (P<0.05);the contents of NADPH, HK2 and PFKFB3 in serum and the protein expression levels of HIF-1α, PKM2 and LDHA in synovial tissue were decreased (P<0.05) in inhibitor group and HRN group. Compared with the inhibitor group, the synovial pathological score was significantly increased (P<0.05), positive expressions of TNF-α, IL-1ß, IL-6 and IL-17, the content of lactic acid in synovial tissue, the contents of NADPH, HK2 and PFKFB3 in serum, and the protein expression levels of HIF-1α, PKM2 and LDHA in synovial tissue were increased (all P<0.05) in HRN group. CONCLUSIONS: HRN can increase the pain threshold, reduce the knee circumference and inhibit the inflammatory response in rabbits with cold syndrome of RA. The possible mechanism is related to the down-regulation of HIF-1α and glycolysis activity.


Subject(s)
Acupuncture Therapy , Arthritis, Rheumatoid , Glycolysis , Hypoxia-Inducible Factor 1, alpha Subunit , Animals , Rabbits , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Humans , Arthritis, Rheumatoid/therapy , Arthritis, Rheumatoid/metabolism , Arthritis, Rheumatoid/genetics , Male , Female , Tumor Necrosis Factor-alpha/metabolism , Tumor Necrosis Factor-alpha/genetics , Acupuncture Points , Interleukin-6/genetics , Interleukin-6/metabolism
7.
J Hazard Mater ; 475: 134917, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38889472

ABSTRACT

Crystal facet and defect engineering are crucial for designing heterogeneous catalysts. In this study, different solvents were utilized to generate NiO with distinct shapes (hexagonal layers, rods, and spheres) using nickel-based metal-organic frameworks (MOFs) as precursors. It was shown that the exposed crystal facets of NiO with different morphologies differed from each other. Various characterization techniques and density functional theory (DFT) calculations revealed that hexagonal-layered NiO (NiO-L) possessed excellent low-temperature reducibility and oxygen migration ability. The (111) crystal plane of NiO-L contained more lattice defects and oxygen vacancies, resulting in enhanced propane oxidation due to its highest O2 adsorption energy. Furthermore, the higher the surface active oxygen species and surface oxygen vacancy concentrations, the lower the C-H activation energy of the NiO catalyst and hence the better the catalytic activity for the oxidation of propane. Consequently, NiO-L exhibited remarkable catalytic activity and good stability for propane oxidation. This study provided a simple strategy for controlling NiO crystal facets, and demonstrated that the oxygen defects could be more easily formed on NiO(111) facets, thus would be beneficial for the activation of C-H bonds in propane. In addition, the results of this work can be extended to the other fields, such as propane oxidation to propene, fuel cells, and photocatalysis.

8.
Nucleic Acids Res ; 52(W1): W299-W305, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38769057

ABSTRACT

A key challenge in pathway design is finding proper enzymes that can be engineered to catalyze a non-natural reaction. Although existing tools can identify potential enzymes based on similar reactions, these tools encounter several issues. Firstly, the calculated similar reactions may not even have the same reaction type. Secondly, the associated enzymes are often numerous and identifying the most promising candidate enzymes is difficult due to the lack of data for evaluation. Thirdly, existing web tools do not provide interactive functions that enable users to fine-tune results based on their expertise. Here, we present REME (https://reme.biodesign.ac.cn/), the first integrated web platform for reaction enzyme mining and evaluation. Combining atom-to-atom mapping, atom type change identification, and reaction similarity calculation enables quick ranking and visualization of reactions similar to an objective non-natural reaction. Additional functionality enables users to filter similar reactions by their specified functional groups and candidate enzymes can be further filtered (e.g. by organisms) or expanded by Enzyme Commission number (EC) or sequence homology. Afterward, enzyme attributes (such as kcat, Km, optimal temperature and pH) can be assessed with deep learning-based methods, facilitating the swift identification of potential enzymes that can catalyze the non-natural reaction.


Subject(s)
Enzymes , Software , Enzymes/chemistry , Enzymes/metabolism , Data Mining/methods , Internet , Deep Learning , Biocatalysis
9.
J Leukoc Biol ; 2024 May 03.
Article in English | MEDLINE | ID: mdl-38700080

ABSTRACT

Precise synapse elimination is essential for the establishment of a fully developed neural circuit during brain development and higher function in adult brain. Beyond immune and nutrition support, recent groundbreaking studies have revealed that phagocytic microglia and astrocytes can actively and selectively eliminate synapses in normal and diseased brains, thereby mediating synapse loss and maintaining circuit homeostasis. Multiple lines of evidence indicate that the mechanisms of synapse elimination by phagocytic glia are not universal but rather depend on specific contexts and detailed neuron-glia interactions. The mechanism of synapse elimination by phagocytic glia is dependent on neuron-intrinsic factors, many innate immune and local apoptosis related molecules. During development, microglial synapse engulfment in the visual thalamus is primarily influenced by the classic complement pathway, whereas in the barrel cortex, the fractalkine pathway is dominant. In Alzheimer's disease, microglia employ complement-dependent mechanisms for synapse engulfment in tauopathy and early ß-amyloid pathology. But microglia are not involved in synapse loss at late ß-amyloid stages. Phagocytic microglia also engulfment synapses in complement dependent way in schizophrenia, anxiety and stress. Besides, phagocytic astrocytes engulf synapses in a MEGF10 dependent way during visual development, memory and stroke. Furthermore, the mechanism of a phenomenon that phagocytes selectively eliminating excitatory and inhibitory synapses is also emphasized in this review. We hypothesize that elucidating context-dependent synapse elimination by phagocytic microglia and astrocytes may reveal the molecular basis of synapse loss in neural disorders and provide a rationale for developing novel candidate therapies that target synapse loss and circuit homeostasis.

10.
BMJ Open ; 14(5): e081840, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38772896

ABSTRACT

OBJECTIVE: Although stroke is prevalent among older people, there is a rising incidence among the younger subpopulations, particularly middle-aged adults. A healthy diet is one of the key modifiable factors to primary prevention of stroke among these subpopulations, yet there is limited understanding of the dietary habits among middle agers who have the risk factor(s) but no occurrence of stroke. This study aims to explore the views on perceptions and the self-management of middle-aged adults at risk of stroke on a healthy diet and to identify the enablers and barriers that could inform the future development of dietary interventions. DESIGN: This study used an interpretive descriptive qualitative design, employing semistructured purposive sampling for focus group discussions. Thematic analysis was conducted on the transcribed interviews and field notes, facilitated by NVivo 12.0 Plus software. SETTING: Community settings in Zhengzhou City, Henan Province. PARTICIPANTS: Middle-aged adults (aged 45-59) were identified as at risk of stroke due to the presence of one or more modifiable risk factors. RESULT: A total of seven focus group discussions were audio recorded. Four main themes emerged, which were: (1) cognitive understanding of a healthy diet; (2) dietary practices; (3) knowledge acquisition and (4) barriers to dietary adherence. CONCLUSIONS: The middle-aged adults at risk of stroke were generally aware of the risk and attempted to practise healthy eating. The existing educational programmes on following a healthy diet in the prevention of disease need to be made more comprehensible, accessible and equitable, especially for those from socioeconomically disadvantaged communities.


Subject(s)
Diet, Healthy , Focus Groups , Health Knowledge, Attitudes, Practice , Qualitative Research , Self-Management , Stroke , Humans , Stroke/prevention & control , Stroke/psychology , China/epidemiology , Middle Aged , Male , Female , Self-Management/psychology , Risk Factors
11.
BMC Genomics ; 25(1): 354, 2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38594645

ABSTRACT

The homeodomain-leucine zipper (HD-Zip) gene family plays a pivotal role in plant development and stress responses. Nevertheless, a comprehensive characterization of the HD-Zip gene family in kiwifruit has been lacking. In this study, we have systematically identified 70 HD-Zip genes in the Actinidia chinensis (Ac) genome and 55 in the Actinidia eriantha (Ae) genome. These genes have been categorized into four subfamilies (HD-Zip I, II, III, and IV) through rigorous phylogenetic analysis. Analysis of synteny patterns and selection pressures has provided insights into how whole-genome duplication (WGD) or segmental may have contributed to the divergence in gene numbers between these two kiwifruit species, with duplicated gene pairs undergoing purifying selection. Furthermore, our study has unveiled tissue-specific expression patterns among kiwifruit HD-Zip genes, with some genes identified as key regulators of kiwifruit responses to bacterial canker disease and postharvest processes. These findings not only offer valuable insights into the evolutionary and functional characteristics of kiwifruit HD-Zips but also shed light on their potential roles in plant growth and development.


Subject(s)
Actinidia , Homeodomain Proteins , Homeodomain Proteins/genetics , Genome, Plant , Phylogeny , Actinidia/genetics , Leucine Zippers/genetics , Gene Expression Regulation, Plant , Plant Proteins/genetics , Gene Expression Profiling
12.
Nat Commun ; 15(1): 2974, 2024 Apr 06.
Article in English | MEDLINE | ID: mdl-38582895

ABSTRACT

Linear ubiquitination catalyzed by HOIL-1-interacting protein (HOIP), the key component of the linear ubiquitination assembly complex, plays fundamental roles in tissue homeostasis by executing domain-specific regulatory functions. However, a proteome-wide analysis of the domain-specific interactome of HOIP across tissues is lacking. Here, we present a comprehensive mass spectrometry-based interactome profiling of four HOIP domains in nine mouse tissues. The interaction dataset provides a high-quality HOIP interactome resource with an average of approximately 90 interactors for each bait per tissue. HOIP tissue interactome presents a systematic understanding of linear ubiquitination functions in each tissue and also shows associations of tissue functions to genetic diseases. HOIP domain interactome characterizes a set of previously undefined linear ubiquitinated substrates and elucidates the cross-talk among HOIP domains in physiological and pathological processes. Moreover, we show that linear ubiquitination of Integrin-linked protein kinase (ILK) decreases focal adhesion formation and promotes the detachment of Shigella flexneri-infected cells. Meanwhile, Hoip deficiency decreases the linear ubiquitination of Smad ubiquitination regulatory factor 1 (SMURF1) and enhances its E3 activity, finally causing a reduced bone mass phenotype in mice. Overall, our work expands the knowledge of HOIP-interacting proteins and provides a platform for further discovery of linear ubiquitination functions in tissue homeostasis.


Subject(s)
Ubiquitin-Protein Ligases , Ubiquitin , Animals , Mice , Homeostasis , NF-kappa B/metabolism , Ubiquitin/metabolism , Ubiquitin-Protein Ligases/metabolism , Ubiquitination
13.
Nanotechnology ; 35(31)2024 May 17.
Article in English | MEDLINE | ID: mdl-38640911

ABSTRACT

The polar channels formed by the curing of waterborne anticorrosive coatings compromise their water resistance, leading to coating degradation and metal corrosion. To enhance the anticorrosive performance of waterborne coatings, this study proposed a novel method of depositing ultrathin Al2O3films on the surface of waterborne epoxy coatings by atomic layer deposition, a technique that can modify the surface properties of polymer materials by depositing functional films. The Al2O3-modified coatings exhibited improved sealing and barrier properties by closing the polar channels and surface defects and cracks. The surface structure and morphology of the modified coatings were characterized by x-ray photoelectron spectroscopy and scanning electron microscopy. The hydrophilicity and corrosion resistance of the modified coatings were evaluated by water contact angle measurement, Tafel polarization curve, and electrochemical impedance spectroscopy. The results indicated that the water contact angle of the Al2O3-modified coating increased by 48° compared to the unmodified coating, and the protection efficiency of the modified coating reached 99.81%. The Al2O3-modified coating demonstrated high anticorrosive efficiency and potential applications for metal anticorrosion in harsh marine environments.

14.
Mol Biotechnol ; 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38664305

ABSTRACT

This study aimed to investigate the mechanisms of LACTB2 in colorectal cancer (CRC). Microarrays and sequencing data of CRC were acquired from UCSC Xena, GTEx, Gene Expression Omnibus, and TCGA. Pooled analysis of the mRNA expression of LACTB2 in CRC was performed using Stata software. The protein expression of LACTB2 in CRC tissues was evaluated by immunohistochemistry. The relationship between immune cell infiltration and LACTB2 expression was investigated using CIBERSORT. The potential signaling pathways and biological mechanisms of LACTB2 were explored using GSEA, KEGG, and GO. Subsequently, further screening of small molecular compounds with potential therapeutic effects on CRC was conducted through the HERB database, followed by molecular docking studies of these compounds with the LACTB2 protein. The integration and analysis of expression data obtained from 2294 CRC samples and 1286 noncancerous colorectal samples showed that LACTB2 was highly expressed in CRC. Immunohistochemistry performed on in-house tissue samples confirmed that LACTB2 protein expression was upregulated in CRC. CIBERSORT revealed lower B cell infiltration levels in the high LACTB2 expression group than in the low expression group. GO, KEGG, and GSEA analyses showed that LACTB2 expression and genes positively correlating with it were mainly related to DNA synthesis and repair, mitochondrial translational elongation and translational termination, phosphorylation, and mTORC1 signaling. Finally, molecular docking simulations confirmed the ability of quercitin to target and bind to LACTB2. This is the first study to demonstrate that LACTB2 is upregulated in CRC. LACTB2 promotes colorectal tumorigenesis and tumor progression.

15.
Behav Sci (Basel) ; 14(4)2024 Apr 14.
Article in English | MEDLINE | ID: mdl-38667120

ABSTRACT

With the increased emphasis on competition in academic settings, anxiety is becoming more common, which inevitably has some impact on students' learning processes and results. This study aimed to explore how competition-induced anxiety influences students' subjective cognitive load (SCL), attention levels, and test scores. We also investigated the mediating role of the behavioral inhibition system/behavioral activation system (BIS/BAS) in those factors. A total of 101 college students were recruited in Study 1 to learn from five micro-lectures from massive open online courses (MOOCs) under competitive and non-competitive conditions. The results showed that participants' state anxiety (SA) scores were higher after the experiment, participants under the competition condition had higher test scores, and the relationship between SA/ trait anxiety (TA) and SCL could be mediated by the BIS. To obtain more objective data on learning processes (attention levels), we conducted Study 2, which collected behavioral and EEG data from 42 college students during the online learning. The results showed that the competition group had higher SA, lower attention levels, and worse test scores, and the relationship between SA/TA and attention levels could be mediated through the BIS. The present study not only expands previous research by finding that BIS functioning plays an important role in the effects of anxiety on cognitive load and attention but also offers implications for using competitive strategies to motivate students according to their aptitudes.

16.
Neuropharmacology ; 252: 109946, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38599494

ABSTRACT

The spontaneous firing activity of nigral dopaminergic neurons is associated with some important roles including modulation of dopamine release, expression of tyrosine hydroxylase (TH), as well as neuronal survival. The decreased neuroactivity of nigral dopaminergic neurons has been revealed in Parkinson's disease. Central glucagon-like peptide-1 (GLP-1) functions as a neurotransmitter or neuromodulator to exert multiple brain functions. Although morphological studies revealed the expression of GLP-1 receptors (GLP-1Rs) in the substantia nigra pars compacta, the possible modulation of GLP-1 on spontaneous firing activity of nigral dopaminergic neurons is unknown. The present extracellular in vivo single unit recordings revealed that GLP-1R agonist exendin-4 significantly increased the spontaneous firing rate and decreased the firing regularity of partial nigral dopaminergic neurons of adult male C57BL/6 mice. Blockade of GLP-1Rs by exendin (9-39) decreased the firing rate of nigral dopaminergic neurons suggesting the involvement of endogenous GLP-1 in the modulation of firing activity. Furthermore, the PKA and the transient receptor potential canonical (TRPC) 4/5 channels are involved in activation of GLP-1Rs-induced excitatory effects of nigral dopaminergic neurons. Under parkinsonian state, both the exogenous and endogenous GLP-1 could still induce excitatory effects on the surviving nigral dopaminergic neurons. As the mild excitatory stimuli exert neuroprotective effects on nigral dopaminergic neurons, the present GLP-1-induced excitatory effects may partially contribute to its antiparkinsonian effects.


Subject(s)
Action Potentials , Dopaminergic Neurons , Exenatide , Glucagon-Like Peptide 1 , Glucagon-Like Peptide-1 Receptor , Mice, Inbred C57BL , Substantia Nigra , Animals , Male , Dopaminergic Neurons/drug effects , Dopaminergic Neurons/metabolism , Glucagon-Like Peptide 1/metabolism , Glucagon-Like Peptide 1/pharmacology , Exenatide/pharmacology , Substantia Nigra/drug effects , Substantia Nigra/metabolism , Glucagon-Like Peptide-1 Receptor/metabolism , Glucagon-Like Peptide-1 Receptor/agonists , Action Potentials/drug effects , Action Potentials/physiology , Mice , Venoms/pharmacology , Peptides/pharmacology , Parkinsonian Disorders/metabolism , Parkinsonian Disorders/physiopathology , Peptide Fragments/pharmacology , Cyclic AMP-Dependent Protein Kinases/metabolism
17.
J Phys Chem B ; 128(16): 3807-3823, 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38605466

ABSTRACT

The origin of highly efficient asymmetric aminohydroxylation of styrene catalyzed by engineered cytochrome c is investigated by the developed Atom-Bond Electronegativity Equalization Method polarizable force field (ABEEM PFF), which is a combined outcome of electronic and steric effects. Model molecules were used to establish the charge parameters of the ABEEM PFF, for which the bond-stretching and angle-bending parameters were obtained by using a combination of modified Seminario and scan methods. The interactions between carbon-radical Fe-porphyrin (FePP) and waters are simulated by molecular dynamics, which shows a clear preference for the pre-R over the pre-S. This preference is attributed to the hydrogen-bond between the mutated 100S and 101P residues as well as van der Waals interactions, enforcing a specific conformation of the carbon-radical FePP complex within the binding pocket. Meanwhile, the hydrogen-bond between water and the nitrogen atom in the active intermediate dictates the stereochemical outcome. Quantum mechanics/molecular mechanics (QM/MM (ABEEM PFF)) and free-energy perturbation calculations elucidate that the 3RTS is characterized by sandwich-like structure among adjacent amino acid residues, which exhibits greater stability than crowed arrangement in 3STS and enables the R enantiomer to form more favorably. Thus, this study provides mechanistic insight into the catalytic reaction of hemoproteins.


Subject(s)
Cytochromes c , Molecular Dynamics Simulation , Quantum Theory , Stereoisomerism , Cytochromes c/chemistry , Cytochromes c/metabolism , Hydrolysis , Carbon/chemistry , Protein Engineering , Hydrogen Bonding , Biocatalysis , Metalloporphyrins/chemistry , Metalloporphyrins/metabolism
18.
Forensic Sci Int ; 357: 111974, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38447346

ABSTRACT

Afghanistan and Myanmar are two overwhelming opium production places. In this study, rapid and efficient methods for distinguishing opium from Afghanistan and Myanmar were developed using infrared spectroscopy (IR) coupled with multiple machine learning (ML) methods for the first time. A total of 146 authentic opium samples were analyzed by mid-IR (MIR) and near-IR (NIR), within them 116 were used for model training and 30 were used for model validation. Six ML methods, including partial least squares discriminant analysis (PLS-DA), orthogonal PLS-DA (OPLS-DA), k-nearest neighbour (KNN), support vector machine (SVM), random forest (RF), and artificial neural networks (ANNs) were constructed and compared to get the best classification effect. For MIR data, the average of precision, recall and f1-score for all classification models were 1.0. For NIR data, the average of precision, recall and f1-score for different classification models ranged from 0.90 to 0.94. The comparison results of six ML models for MIR and NIR data showed that MIR was more suitable for opium geography classification. Compared with traditional chromatography and mass spectrometry profiling methods, the advantages of MIR are simple, rapid, cost-effective, and environmentally friendly. The developed IR chemical profiling methodology may find wide application in classification of opium from Afghanistan and Myanmar, and also to differentiate them from opium originating from other opium producing countries. This study presented new insights into the application of IR and ML to rapid drug profiling analysis.


Subject(s)
Opium , Spectroscopy, Near-Infrared , Spectroscopy, Near-Infrared/methods , Afghanistan , Myanmar , Spectrophotometry, Infrared , Discriminant Analysis , Least-Squares Analysis , Support Vector Machine
19.
Phytomedicine ; 128: 155415, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38503151

ABSTRACT

BACKGROUND: Chichoric acid (CA) is a major active ingredient found in chicory and Echinacea. As a derivative of caffeic acid, it has various pharmacological effects. PURPOSE: Due to the unclear etiology and disease mechanisms, effective treatment methods for ulcerative colitis (UC) are currently lacking. The study investigated the therapeutic effects of the folate-chicory acid liposome on both LPS-induced macrophage inflammation models and dextran sulfate sodium (DSS)-induced mouse UC models. METHODS: Folate-chicory acid liposome was prepared using the double emulsion ultrasonic method with the aim of targeting folate receptors specifically expressed on macrophages. The study investigated the therapeutic effects of the folate-chicory acid liposome on both LPS-induced macrophage inflammation models and DSS -induced mouse UC models. Furthermore, the effects of the liposomes on macrophage polarization and their underlying mechanisms in UC were explored. RESULTS: The average particle size of folate-chicory acid liposome was 120.4 ± 0.46 nm, with an encapsulation efficiency of 77.32 ± 3.19 %. The folate-chicory acid liposome could alleviate macrophage apoptosis induced by LPS, decrease the expression of inflammatory factors in macrophages, enhance the expression of anti-inflammatory factors, inhibit macrophage polarization towards the M1 phenotype, and mitigate cellular inflammation in vetro. In vivo test, folate-chicory acid liposome could attenuate clinical symptoms, increased colon length, reduced DAI scores, CMDI scores, and alleviated the severity of colonic histopathological damage in UC mice. Furthermore, it inhibited the polarization of macrophages towards the M1 phenotype in the colon and downregulated the TLR4/NF-κB signaling pathway, thereby ameliorating UC in mice. CONCLUSION: Folate-chicory acid liposome exhibited a uniform particle size distribution and high encapsulation efficiency. It effectively treated UC mice by inhibiting the polarization of macrophages towards the M1 phenotype in the colon and downregulating the TLR4/NF-κB signaling pathway.


Subject(s)
Caffeic Acids , Colitis, Ulcerative , Folic Acid , Lipopolysaccharides , Liposomes , Macrophages , NF-kappa B , Signal Transduction , Toll-Like Receptor 4 , Animals , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/chemically induced , Folic Acid/pharmacology , Folic Acid/chemistry , Folic Acid/analogs & derivatives , Toll-Like Receptor 4/metabolism , Mice , NF-kappa B/metabolism , Signal Transduction/drug effects , Macrophages/drug effects , Caffeic Acids/pharmacology , Caffeic Acids/chemistry , Male , RAW 264.7 Cells , Disease Models, Animal , Dextran Sulfate , Succinates/pharmacology , Succinates/chemistry , Mice, Inbred C57BL , Apoptosis/drug effects , Anti-Inflammatory Agents/pharmacology
20.
Nanotechnology ; 35(26)2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38522103

ABSTRACT

Titanium oxide (TiO2) coated polyimide has broad application prospects under extreme conditions. In order to obtain a high-quality ultra-thin TiO2coating on polyimide by atomic layer deposition (ALD), the polyimide was activated byin situoxygen plasma. It was found that a large number of polar oxygen functional groups, such as carboxyl, were generated on the surface of the activated polyimide, which can significantly promote the preparation of TiO2coating by ALD. The nucleation and growth of TiO2were studied by x-ray photoelectron spectroscopy monitoring and scanning electron microscopy observation. On the polyimide activated by oxygen plasma, the size of TiO2nuclei decreased and the quantity of TiO2nuclei increased, resulting in the growth of a highly uniform and dense TiO2coating. This coating exhibited excellent resistance to atomic oxygen. When exposed to 3.5 × 1021atom cm-2atomic oxygen flux, the erosion yield of the polyimide coated with 100 ALD cycles of TiO2was as low as 3.0 × 10-25cm3/atom, which is one order less than that of the standard POLYIMIDE-ref Kapton®film.

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