Integrative profiling of metabolome and transcriptome of skeletal muscle after acute exercise intervention in mice

This study aims to explore the molecular regulatory mechanisms of acute exercise in the skeletal muscle of mice. Male C57BL/6 mice were randomly assigned to the control group, and the exercise group, which were sacrificed immediately after an acute bout of exercise. The study was conducted to investigate the metabolic and transcriptional profiling in the quadriceps muscles of mice. The results demonstrated the identification of 34 differentially expressed metabolites (DEMs), with 28 upregulated and 6 downregulated, between the two groups. Metabolic pathway analysis revealed that these DEMs were primarily enriched in several, including the citrate cycle, propanoate metabolism, and lysine degradation pathways. In addition, the results showed a total of 245 differentially expressed genes (DEGs), with 155 genes upregulated and 90 genes downregulated. KEGG analysis indicated that these DEGs were mainly enriched in various pathways such as ubiquitin mediated proteolysis and FoxO signaling pathway. Furthermore, the analysis revealed significant enrichment of DEMs and DEGs in signaling pathways such as protein digestion and absorption, ferroptosis signaling pathway. In summary, the identified multiple metabolic pathways and signaling pathways were involved in the exercise-induced physiological regulation of skeletal muscle, such as the TCA cycle, oxidative phosphorylation, protein digestion and absorption, the FoxO signaling pathway, ubiquitin mediated proteolysis, ferroptosis signaling pathway, and the upregulation of KLF-15, FoxO1, MAFbx, and MuRF1 expression could play a critical role in enhancing skeletal muscle proteolysis

Exploring the mechanism of aloe-emodin in the treatment of liver cancer through network pharmacology and cell experiments

Objective: Aloe-emodin (AE) is an anthraquinone compound extracted from the rhizome of the natural plant rhubarb. Initially, it was shown that AE exerts an anti-inflammatory effect. Further studies revealed its antitumor activity against various types of cancer. However, the mechanisms underlying these properties remain unclear. Based on network pharmacology and molecular docking, this study investigated the molecular mechanism of AE in the treatment of hepatocellular carcinoma (HCC), and evaluated its therapeutic effect through in vitro experiments.Methods: CTD, Pharmmapper, SuperPred and TargetNet were the databases to obtain potential drug-related targets. DisGenet, GeneCards, OMIM and TTD were used to identify potential disease-related targets. Intersection genes for drugs and diseases were obtained through the Venn diagram. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of intersecting genes were conducted by the website of Bioinformatics. Intersection genes were introduced into STRING to construct a protein-protein interaction network, while the Cytoscape3.9.1 software was used to visualize and analyze the core targets. AutoDock4.2.6 was utilized to achieve molecular docking between drug and core targets. In vitro experiments investigated the therapeutic effects and related mechanisms of AE.Results: 63 overlapped genes were obtained and GO analysis generated 3,646 entries by these 63 intersecting genes. KEGG analysis mainly involved apoptosis, proteoglycans in cancer, TNF signaling pathway, TP53 signaling pathway, PI3K-AKT signaling pathway, etc. AKT1, EGFR, ESR1, TP53, and SRC have been identified as core targets because the binding energies of them between aloe-emodin were less than -5 kcal/Mol.The mRNA and protein expression, prognosis, mutation status, and immune infiltration related to core targets were further revealed. The involvement of AKT1 and EGFR, as well as the key target of the PI3K-AKT signaling pathway, indicated the importance of this signaling pathway in the treatment of HCC using AE. The results of the Cell Counting Kit-8 assay and flow analysis demonstrated the therapeutic effect of AE. The downregulation of EGFR, PI3KR1, AKT1, and BCL2 in mRNA expression and PI3KR1, AKT,p-AKT in protein expression confirmed our hypothesis.Conclusion: Based on network pharmacology and molecular docking, our study initially showed that AE exerted a therapeutic effect on HCC by modulating multiple signaling pathways. Various analyses confirmed the antiproliferative activity and pro-apoptotic effect of AE on HCC through the PI3K-AKT signaling pathway. This study revealed the therapeutic mechanism of AE in the treatment of HCC through a novel approach, providing a theoretical basis for the clinical application of AE

A Three-Dimensional Inorganic Analogue of 9,10-Diazido-9,10-Diboraanthracene: A Lewis Superacidic Azido Borane with Reactivity and Stability

Herein, we report the facile synthesis of a three-dimensional (3D) inorganic analogue of 9,10-diazido-9,10-dihydrodiboraantracene, which turned out to be a monomer in both the solid and solution state, and thermally stable up to 230 °C, representing a rare example of azido borane with boosted Lewis acidity and stability in one. Apart from the classical acid-base and Staudinger reactions, E−H bond activation (E=B, Si, Ge) was investigated. While the reaction with B−H (9-borabicyclo[3.3.1]nonane) led directly to the 1,1-addition on N$_{α}$ upon N$_{2}$ elimination, the Si−H (Et$_{3}$SiH, PhMe$_{2}$SiH) activation proceeded stepwise via 1,2-addition, with the key intermediates 5$_{int}$ and 6$_{int}$ being isolated and characterized. In contrast, the cooperative Ge−H was reversible and stayed at the 1,2-addition step

Effects of Hypoxia Stress on Growth, Root Respiration, and Metabolism of Phyllostachys praecox

Hypoxia affects plant growth, hormone content, various enzyme activities, cell structure, peroxide production, and metabolic level, therefore reducing crop yield. This study assessed the physiological, biochemical, and metabolic characteristics of Phyllostachys praecox. Results revealed that hypoxia stress treatment significantly inhibited plant growth. Leaf chlorophyll contents was initially improved and then reduced with plant growth time. Under hypoxia stress, the root activity significantly was reduced, leading to the decrease in the nutrient absorption and transport. Yet, with low oxygen concentration, the contents of ethanol, acetaldehyde, and lactic acid were improved. With hypoxia stress, phospholipids and amino acids were the main metabolites of Phyllostachys praecox. Glycosphospholipid metabolism is the key pathway in responding to hypoxia stress significantly (p < 0.05), and lysophosphatidlycholine (lysoPC) and phosphatidylcholines (PC) in the metabolites of this metabolic pathway were significantly enhanced. Our study reveals the mechanism of Phyllostachys praecox cell membrane responding to hypoxia stress based on molecular level. This is conducive to finding targeted solutions to improve the productivity of Phyllostachys praecox to better optimize a mulching approach in the bamboo forest

Application of peripheral blood cytokine and immunoglobulin detection in ACTH therapy for the treatment of infantile spasms

ObjectiveThis research aims to investigate the levels of lymphocytes, immunoglobulins, and cytokines in children with infantile spasms (IS) before and after adrenocorticotropic hormone (ACTH) therapy and to explore the application of these markers in evaluating the therapeutic effects of ACTH on infantile spasms.MethodsFrom May to November 2022, 35 children initially diagnosed with IS and treated at our hospital were regarded as the observation group, and 35 healthy children who underwent physical examination at our hospital during the same period were regarded as the control group. Children in the observation group received intramuscular injections of ACTH for 2 weeks. Fasting venous blood was collected from the control group and the observation group before and after ACTH therapy. Serum levels of immunoglobulins IgG, IgA, and IgM in serum were detected by immunoturbidimetry. T-cell subsets (CD3+, CD3+CD4+, and CD3+CD8+) and B-cell subsets [CD3−CD19+ and CD3−CD16+CD56+ natural killer (NK) cells] were detected by flow cytometry, and the ratio of CD3+CD4+/CD3+CD8+ was calculated. Serum levels of interleukin-1β (IL-1β), interleukin-2R (IL-2R), and interleukin-6 (IL-6) cytokines were detected by the enzyme-linked immunosorbent assay, and changes in serum cytokine and immunoglobulin levels in the two groups were compared before therapy, whereas in observation group one, these comparisons were made both before and after ACTH therapy.ResultsCompared to the control group, the observation group showed significantly increased serum levels of immunoglobulins IgG and IgM before therapy, while the level of IgA was significantly decreased (p < 0.05). Also, the percentage of CD3−CD19+ B cells was significantly increased, while the percentages of CD3+ T cells and CD3+CD4+ T cells were significantly decreased (p < 0.05). The percentages of CD3+CD8+ T cells, CD3−CD16+CD56+ NK cells, and CD3+CD4+/CD3+CD8+ cells did not change significantly (p > 0.05); the levels of cytokines IL-1 β, IL-2R, and IL-6 were significantly increased (p < 0.05). Compared to levels before treatment, the serum level of immunoglobulin IgG in the observation group after ACTH therapy was significantly reduced (p < 0.05), while the IgA and IgM levels did not change significantly (p > 0.05). The percentages of CD3+ T cells and CD3+CD4+ T cells were significantly increased, while the percentages of CD3−CD16+CD56+ NK cells and CD3−CD19+ B cells were significantly decreased (p < 0.05); however, the percentages of CD3+CD8+ T cells and the CD3+CD4+/CD3+CD8+ ratio did not change significantly (p > 0.05). Furthermore, the levels of cytokines IL-1 β, IL-2R, and IL-6 were significantly reduced (p < 0.05).ConclusionChildren with IS exhibit immune dysfunction, and the changes in serological immune indices after ACTH treatment indicate that ACTH may control seizures in IS children by regulating and improving immune dysfunction. Therefore, the therapeutic effects of ACTH on IS can be evaluated by detecting the levels of cytokines and immunoglobulins

Effect of Hypoxic Stress and Levels of Mn on the Physiology and Biochemistry of <i>Phyllostachys praecox</i>

Hypoxic environments have an adverse effect on the growth and development of P. praecox, and this is accompanied by the production of reducing substances such as Fe and Mn. In this study, the effect of hypoxic stress and Mn concentrations on leaf chlorophyll contents, root morphology, root activity, element absorption, antioxidant enzymes, and respiratory enzyme system of P. praecox were evaluated in a hydroponics environment. The results revealed that application of Mn2+ during hypoxic stress enhanced leaf chlorophyll contents and boosted up the indexes of the root system. The root activity of P. praecox was reduced with stresses of hypoxia. The treatment of Mn2+ initially improved and then decreased the root activity of P. praecox, and attained its maximum with application of 300 μmol/L Mn2+ compared with control. The indexes of antioxidant enzymes of P. praecox were higher than that of 8 mg/L oxygen concentrations except for variable superoxide dismutase (SOD) in the treatment of 300 μmol/L Mn2+ with hypoxia stress. The application of Mn had inhibited the absorption of mineral elements in P. praecox. The activities of pyruvate decarboxylase (PDC), alcohol dehydrogenase (ADH), and lactic dehydrogenase (LDH) were initially improved and then diminished with hypoxia stress. It is concluded that hypoxia is a key factor affecting the growth and degradation of P. praecox, while combining it with the increase of Mn concentration enhances the damage to Phyllostachys pubescens. Our research is helpful for the sustainable management and scientific fertilization management of Phyllostachys praecox

Improvement of pharmacokinetics behavior of apocynin by nitrone derivatization: comparative pharmacokinetics of nitrone-apocynin and its parent apocynin in rats.

Apocynin, a potent inhibitor of NADPH-oxidase, was widely studied for activities in diseases such as inflammation-mediated disorders, asthma and cardiovascular diseases. In our recent study, a novel nitrone derivative of apocynin, AN-1, demonstrated potent inhibition to oxidative injury and to high expression of gp91(phox) subunit of NADPH-oxidase induced by tert-butyl hydroperoxide (t-BHP) in RAW 264.7 macrophage cells, and displayed promising preclinical protective effect against lipopolysaccharide (LPS)-induced acute lung injury in rats. In this work, the pharmacokinetic behaviors of AN-1 in Sprague-Dawley rats with single intravenous and intragastric doses were investigated for further development. Furthermore, apocynin's pharmacokinetics remain lacking, even though its pharmacological action has been extensively evaluated. The pharmacokinetics of parent apocynin were also comparatively characterized. A simple HPLC method was developed and validated to determine both AN-1 and apocynin in rat plasma. The chromatographic separation was achieved on an Agilent HC-C18 column (250 mm×4.6 mm, 5 µm) at an isocratic flow rate of 1.0 mL/min, with the mobile phase of methanol and water (53∶47, v/v) and the UV detection set at 279 nm. Good linearity was established over the concentration range of 0.1-500 µg/mL for AN-1 and 0.2-100 µg/mL for apocynin. The absolute recovery, precision and accuracy were satisfactory. Compared with the parent compound apocynin, AN-1 yielded a much longer T1/2 (AN-1 179.8 min, apocynin 6.1 min) and higher AUC0-t (AN-1 61.89 mmol/L·min, apocynin 2.49 mmol/L·min) after equimolar intravenous dosing (0.302 mmol/kg). The absolute bioavailability of oral AN-1 was 78%, but that of apocynin was only 2.8%. The significant improvement of pharmacokinetic behavior might be accounted for the effective pharmacodynamic results we documented for the novel nitrone derivative AN-1

Hydrochemical Characteristics and Formation of the Madeng Hot Spring in Yunnan, China

The Madeng hot spring emerges in the central river valley in the northeastern Lanping Basin in Jianchuan county of Yunnan Province in China. Quaternary sand and gravel occur in the valley which is underlain by the red beds consisting of sandstone and mudstone. The temperature of the hot spring is 42.1°C. The spring water has a pH value of 6.41, TDS of 3.98 g/L, F contents of 3.08 mg/L, and H2SiO3 of 35.6 mg/L. The hot water is of SO4•Cl-Na•Ca type. There is a slight hydrogen sulfide odor in the spring water. Stable hydrogen and oxygen isotopes indicate that the hot water is of meteoric origin. It is estimated that the elevation of the recharge area of the hot spring is approximately 3800 m, the age of the hot water is some 140 years, the temperature of the geothermal reservoir is 75°C–80°C, the mixture ratio of cold water is approximately 80%, and the circulation depth of the thermal groundwater is 1870 m. After receiving recharge from infiltration of precipitation in the mountainous recharge areas, the groundwater undergoes a deep circulation, obtains heat from the heat flow, flows upward along the fractured zone, and emerges as an upflow spring through the Quaternary sand and gravel in the central low-lying river valley

Mean Plasma Concentration-Time Profiles of AN-1 and Apocynin in Sprague-Dawley Rats.

<p>Profiles of (A) AN-1 after a single intravenous dose at 20 mg/kg (n = 8), 40 mg/kg (n = 6) and 80 mg/kg (n = 8); (B) AN-1 after a single intragastric dose at 40 mg/kg (n = 6); (C) apocynin after a single intravenous dose at 50 mg/kg (n = 8); (D) apocynin after a single intragastric dose at 50 mg/kg (n = 6). Each point represented as mean ± SD.</p