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Biomacromolecules Dec 2023The excellent combined properties of poly(butylene succinate) (PBS) make it a promising biodegradable plastic. However, the lack of functionality and low impact strength...
The excellent combined properties of poly(butylene succinate) (PBS) make it a promising biodegradable plastic. However, the lack of functionality and low impact strength limit its application. Poly(dimethylsiloxane) (PDMS) was introduced to prepare new high-performance and functional poly(butylene succinate)--poly(dimethylsiloxane) (PBS--PDMS) in this work. The resulting PBS--PDMS was found to possess high molecular weight, narrow molecular weight distribution, and excellent combined performance. PBS--PDMS had good thermal properties. The decomposition temperature of 5% weight loss () increased from 324 to 344 °C, and the temperatures at the maximum weight loss rate () values increased from 385.1 to 396.7 °C. The impact strength increased significantly from 7.8 kJ/m of PBS to 53.9 kJ/m of PBS--PDMS. As the PDMS block endows copolymers with low surface energy and good liquid resistance, PBS--PDMS has excellent antismudge, self-cleaning, and solvent resistance. Finally, to minimize the surface energy, PDMS blocks preferentially enrich the surface, which imparts the polymers with self-cleaning properties.
Topics: Humans; Biocompatible Materials; Polymers; Succinates; Weight Loss
PubMed: 38033158
DOI: 10.1021/acs.biomac.3c00956 -
Archives of Biochemistry and Biophysics Feb 2024Ventilator-induced lung injury (VILI) disturbs the disordered immune system and causes persistent inflammatory damage. 4-octyl itaconate (OI) is a synthetic...
Ventilator-induced lung injury (VILI) disturbs the disordered immune system and causes persistent inflammatory damage. 4-octyl itaconate (OI) is a synthetic cell-permeable itaconate derivative with antioxidant and anti-inflammatory effects. In this study, we assessed whether OI protects against VILI. OI was intraperitoneally injected for three days before mechanical ventilation (MV; 20 ml/kg at 70 breaths/min) for 2 h. Mouse lung vascular endothelial cells (MLVECs) were pretreated with OI (62.5, 125, and 250 μM) prior to cyclic stretch for 4 h. We found that OI attenuated VILI and inflammatory response. OI also increased superoxide dismutase, nuclear factor E2-related factor 2, and heme oxygenase-1 levels, and decreased reactive oxygen species and malondialdehyde levels. Furthermore, OI inhibited the expression of NLR family pyrin domain-containing 3 (NLRP3), caspase-1 p20, apoptosis-associated speck-like protein containing a CARD, and N-terminal fragment of gasdermin D. Therefore, OI attenuates VILI, potentially by suppressing oxidative stress and NLRP3 activation.
Topics: Mice; Animals; NLR Family, Pyrin Domain-Containing 3 Protein; Endothelial Cells; Ventilator-Induced Lung Injury; NF-E2-Related Factor 2; Lung; Succinates
PubMed: 38086523
DOI: 10.1016/j.abb.2023.109853 -
Redox Biology Jun 2024Premature infants often require oxygen supplementation, which can elicit bronchopulmonary dysplasia (BPD) and lead to mitochondrial dysfunction. Mitochondria play...
BACKGROUND
Premature infants often require oxygen supplementation, which can elicit bronchopulmonary dysplasia (BPD) and lead to mitochondrial dysfunction. Mitochondria play important roles in lung development, in both normal metabolism and apoptosis. Enhancing our comprehension of the underlying mechanisms in BPD development can facilitate the effective treatments.
METHODS
Plasma samples from BPD and non-BPD infants were collected at 36 weeks post-menstrual age and used for metabolomic analysis. Based on hyperoxia-induced animal and cell models, changes in mitophagy and apoptosis were evaluated following treatment with itaconic acid (ITA). Finally, the mechanism of action of ITA in lung development was comprehensively demonstrated through rescue strategies and administration of corresponding inhibitors.
RESULTS
An imbalance in the tricarboxylic acid (TCA) cycle significantly affected lung development, with ITA serving as a significant metabolic marker for the outcomes of lung development. ITA improved the morphological changes in BPD rats, promoted SP-C expression, and inhibited the degree of alveolar type II epithelial cells (AEC II) apoptosis. Mechanistically, ITA mainly promotes the nuclear translocation of transcription factor EB (TFEB) to facilitate dysfunctional mitochondrial clearance and reduces apoptosis in AEC II cells by regulating autophagic flux.
CONCLUSION
The metabolic imbalance in the TCA cycle is closely related to lung development. ITA can improve lung development by regulating autophagic flux and promote the nuclear translocation of TFEB, implying its potential therapeutic utility in the treatment of BPD.
Topics: Succinates; Animals; Autophagy; Bronchopulmonary Dysplasia; Rats; Humans; Hyperoxia; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Apoptosis; Mitochondria; Disease Models, Animal; Male; Citric Acid Cycle; Female; Mitophagy; Lung; Infant, Newborn
PubMed: 38554522
DOI: 10.1016/j.redox.2024.103115 -
Clinical and Translational Medicine Apr 2024Spinal cord injury (SCI)-induced neuroinflammation and oxidative stress (OS) are crucial events causing neurological dysfunction. Aconitate decarboxylase 1 (ACOD1) and...
BACKGROUND
Spinal cord injury (SCI)-induced neuroinflammation and oxidative stress (OS) are crucial events causing neurological dysfunction. Aconitate decarboxylase 1 (ACOD1) and its metabolite itaconate (Ita) inhibit inflammation and OS by promoting alkylation of Keap1 to induce Nrf2 expression; however, it is unclear whether there is another pathway regulating their effects in inflammation-activated microglia after SCI.
METHODS
Adult male C57BL/6 ACOD1 mice and their wild-type (WT) littermates were subjected to a moderate thoracic spinal cord contusion. The degree of neuroinflammation and OS in the injured spinal cord were assessed using qPCR, western blot, flow cytometry, immunofluorescence, and trans-well assay. We then employed immunoprecipitation-western blot, chromatin immunoprecipitation (ChIP)-PCR, dual-luciferase assay, and immunofluorescence-confocal imaging to examine the molecular mechanisms of ACOD1. Finally, the locomotor function was evaluated with the Basso Mouse Scale and footprint assay.
RESULTS
Both in vitro and in vivo, microglia with transcriptional blockage of ACOD1 exhibited more severe levels of neuroinflammation and OS, in which the expression of p62/Keap1/Nrf2 was down-regulated. Furthermore, silencing ACOD1 exacerbated neurological dysfunction in SCI mice. Administration of exogenous Ita or 4-octyl itaconate reduced p62 phosphorylation. Besides, ACOD1 was capable of interacting with phosphorylated p62 to enhance Nrf2 activation, which in turn further promoted transcription of ACOD1.
CONCLUSIONS
Here, we identified an unreported ACOD1-p62-Nrf2-ACOD1 feedback loop exerting anti-inflammatory and anti-OS in inflammatory microglia, and demonstrated the neuroprotective role of ACOD1 after SCI, which was different from that of endogenous and exogenous Ita. The present study extends the functions of ACOD1 and uncovers marked property differences between endogenous and exogenous Ita.
KEY POINTS
ACOD1 attenuated neuroinflammation and oxidative stress after spinal cord injury. ACOD1, not itaconate, interacted with p-p62 to facilitate Nrf2 expression and nuclear translocation. Nrf2 was capable of promoting ACOD1 transcription in microglia.
Topics: Animals; Male; Mice; Carboxy-Lyases; Disease Models, Animal; Hydro-Lyases; Mice, Inbred C57BL; Microglia; NF-E2-Related Factor 2; Sequestosome-1 Protein; Spinal Cord Injuries; Succinates
PubMed: 38644791
DOI: 10.1002/ctm2.1661 -
Yeast (Chichester, England) Dec 2023Microbial metabolism offers a wide variety of opportunities to produce chemicals from renewable resources. Employing such processes of industrial biotechnology provides... (Review)
Review
Microbial metabolism offers a wide variety of opportunities to produce chemicals from renewable resources. Employing such processes of industrial biotechnology provides valuable means to fight climate change by replacing fossil feedstocks by renewable substrate to reduce or even revert carbon emission. Several yeast species are well suited chassis organisms for this purpose, illustrated by the fact that the still largest microbial production of a chemical, namely bioethanol is based on yeast. Although production of ethanol and some other chemicals is highly efficient, this is not the case for many desired bulk chemicals. One reason for low efficiency is carbon loss, which decreases the product yield and increases the share of total production costs that is taken by substrate costs. Here we discuss the causes for carbon loss in metabolic processes, approaches to avoid carbon loss, as well as opportunities to incorporate carbon from CO , based on the electron balance of pathways. These aspects of carbon efficiency are illustrated for the production of succinic acid from a diversity of substrates using different pathways.
Topics: Carbon; Biotechnology; Yeasts; Metabolic Engineering
PubMed: 37997485
DOI: 10.1002/yea.3909 -
Andrology Oct 2023Asthenozoospermia is one of the essential causes of male infertility, and its incidence is significantly higher in obese men. Due to its complex etiology and unknown...
BACKGROUND
Asthenozoospermia is one of the essential causes of male infertility, and its incidence is significantly higher in obese men. Due to its complex etiology and unknown pathomechanism, the diagnosis and treatment of obesity-induced asthenozoospermia is a prevalent problem in reproductive medicine.
OBJECTIVE
This study aims to explore major differential metabolites and metabolic pathways in seminal plasma and pathological mechanisms for obesity-induced asthenozoospermia.
MATERIALS AND METHODS
We performed non-target metabolomic studies on the seminal plasma of healthy men with normal semen parameters (HN group, n = 20), obese men with normal semen parameters (ON group, n = 20), and men with obesity-induced asthenozoospermia (OA group, n = 20) based on gas chromatography-mass spectrometry. Metabolic profilings and related pathway analyses were conducted to discriminate differential metabolites and metabolic pathways.
RESULTS
A total of 20 differential metabolites including fructose, succinic acid, aconitic acid, methylmaleic acid, glucopyranose, serine, valine, leucine, phenylalanine, glycine, glutamic acid, alanine, proline and threonine were identified in HN group and ON group; 24 differential metabolites including glucose, fructose, pyruvic acid, citric acid, succinic acid, aconitic acid, glucopyranose, glutamic acid, valine, leucine, glycine, phenylalanine, lysine, citrulline, proline and alanine were produced in OA group and ON group; and 28 differential metabolites including glucose, fructose, citric acid, succinic acid, glucopyranose, valine, glycine, serine, leucine, phenylalanine, alanine, threonine, proline, glutamic acid, citrulline, lysine and tyrosine were produced in OA group and HN group. In addition, abnormal energy metabolism including carbohydrate metabolism (TCA cycle, glycolysis/gluconeogenesis, and pyruvate metabolism) and amino acid metabolism (phenylalanine, tyrosine, and tryptophan biosynthesis, D-glutamine and D-glutamate metabolism; phenylalanine metabolism, etc.) were found in ON group and OA group.
CONCLUSION
Obesity could affect the metabolite composition in seminal plasma and abnormal energy metabolism in seminal plasma mainly including carbohydrate metabolism and amino acid metabolism were closely related to obesity-induced asthenozoospermia.
Topics: Male; Humans; Semen; Asthenozoospermia; Leucine; Lysine; Glutamic Acid; Citrulline; Aconitic Acid; Succinic Acid; Metabolomics; Alanine; Proline; Glycine; Tyrosine; Phenylalanine; Valine; Serine; Threonine; Glucose
PubMed: 36841993
DOI: 10.1111/andr.13412 -
Molecular Oral Microbiology Apr 2024Type 2 diabetes (T2D) is a chronic metabolic disorder in which insulin resistance and impaired insulin secretion result in altered metabolite balance, specifically...
Type 2 diabetes (T2D) is a chronic metabolic disorder in which insulin resistance and impaired insulin secretion result in altered metabolite balance, specifically elevated levels of circulating glucose and succinate, which increases the risk of many pathologies, including periodontitis. Succinate, a tricarboxylic acid (TCA) cycle intermediate, can be produced and metabolized by both host cells and host microbiota, where elevated levels serve as an inflammation and pathogen threat signal through activating the succinate G protein-coupled receptor, SUCNR1. Modulating succinate-induced SUCNR1 signaling remains a promising therapeutic approach for pathologies resulting in elevated levels of succinate, such as T2D and periodontitis. Here, we demonstrate hyperglycemia and elevated intracellular succinate in a T2D mouse model and determine gut microbiome composition. Drawing on previous work demonstrating the ability of a novel SUCNR1 antagonist, compound 7a, to block inflammation and alleviate dysbiosis in a mouse model, we examined if compound 7a has an impact on the growth and virulence gene expression of bacterial and fungal human microbiota in vitro, and if 7a could reduce bone loss in a periodontitis-induced mouse model. T2D mice harbored a significantly different gut microbiome, suggesting the altered metabolite profile of T2D causes shifts in host-microbial community structure, with enrichment in succinate producers and consumers and mucin-degrading bacteria. Bacterial and fungal cultures showed that 7a did not influence growth or virulence gene expression, suggesting the therapeutic effects of 7a are a direct result of 7a interacting with host cells and that alterations in microbial community structure are driven by reduced host SUCNR1 signaling. This work further suggests that targeting SUCNR1 signaling is a promising therapeutic approach in metabolic, inflammatory, or immune disorders with elevated succinate levels.
Topics: Mice; Humans; Animals; Diabetes Mellitus, Type 2; Dysbiosis; Inflammation; Microbiota; Succinic Acid; Succinates; Periodontitis
PubMed: 37715517
DOI: 10.1111/omi.12431 -
Physiological Reports Nov 2023Recently, the gut microbiome has emerged as a potent modulator of exercise-induced systemic adaptation and appears to be crucial for mediating some of the benefits of...
Recently, the gut microbiome has emerged as a potent modulator of exercise-induced systemic adaptation and appears to be crucial for mediating some of the benefits of exercise. This study builds upon previous evidence establishing a gut microbiome-skeletal muscle axis, identifying exercise-induced changes in microbiome composition. Metagenomics sequencing of fecal samples from non-exercise-trained controls or exercise-trained mice was conducted. Biodiversity indices indicated exercise training did not change alpha diversity. However, there were notable differences in beta-diversity between trained and untrained microbiomes. Exercise significantly increased the level of the bacterial species Muribaculaceae bacterium DSM 103720. Computation simulation of bacterial growth was used to predict metabolites that accumulate under in silico culture of exercise-responsive bacteria. We identified acetate and succinate as potential gut microbial metabolites that are produced by Muribaculaceae bacterium, which were then administered to mice during a period of mechanical overload-induced muscle hypertrophy. Although no differences were observed for the overall muscle growth response to succinate or acetate administration during the first 5 days of mechanical overload-induced hypertrophy, acetate and succinate increased skeletal muscle mitochondrial respiration. When given as post-biotics, succinate or acetate treatment may improve oxidative metabolism during muscle hypertrophy.
Topics: Mice; Animals; Succinic Acid; Muscle, Skeletal; Microbiota; Bacteria; Bacteroidetes; Acetates; Hypertrophy
PubMed: 37940330
DOI: 10.14814/phy2.15848 -
Cancer Reports (Hoboken, N.J.) Nov 2023There is an increased risk of colon cancer associated with inflammatory bowel disease (IBD). Dietary fibers (DFs) naturally present in vegetables and whole grains offer...
BACKGROUND AND AIM
There is an increased risk of colon cancer associated with inflammatory bowel disease (IBD). Dietary fibers (DFs) naturally present in vegetables and whole grains offer numerous beneficial effects on intestinal health. However, the effects of refined DFs on intestinal health remain unclear. Therefore, we elucidated the impact of the refined DF inulin on colonic inflammation and tumorigenesis.
METHODS
Four-week-old wild-type (WT) mice were fed diets containing insoluble DF cellulose (control) or refined DF inulin for 4 weeks. A subgroup of mice was then switched to drinking water containing dextran sulfate sodium (DSS, 1.4% wt/vol) for colitis induction. In another subgroup of mice, colitis-associated colorectal cancer (CRC) was initiated with three 7-day alternate cycles of DSS following an initial dose of mutagenic substance azoxymethane (AOM; 7.5 mg/kg body weight; i.p.). Post 7 weeks of AOM treatment, mice were euthanized and examined for CRC development.
RESULTS
Mice consuming inulin-containing diet exhibited severe colitis upon DSS administration, as evidenced by more body weight loss, rectal bleeding, and increased colonic inflammation than the DSS-treated control group. Correspondingly, histological analysis revealed extensive disruption of colon architecture and massive infiltration of immune cells in the inulin-fed group. We next examined the effect of inulin on CRC development. Surprisingly, significant mortality (~50%) was observed in the inulin-fed but not in the control group during the DSS cycle. Consequently, the remaining inulin-fed mice, which completed the study exhibited extensive colon tumorigenesis. Immunohistochemical characterization showed comparatively high expression of the cell proliferation marker Ki67 and activation of the Wnt signaling in tumor sections obtained from the inulin-fed group. Gut microbiota and metabolite analysis revealed expansion of succinate producers and elevated cecal succinate in inulin-fed mice. Human colorectal carcinoma cells (HCT116) proliferated more rapidly when supplemented with succinate in an inflamed environment, suggesting that elevated luminal succinate may contribute to tumorigenesis.
CONCLUSIONS
Our study uncovers that supplementation of diet with refined inulin induces abnormal succinate accumulation in the intestinal lumen, which in part contributes to promoting colon inflammation and tumorigenesis.
Topics: Humans; Animals; Mice; Inulin; Succinic Acid; Dextran Sulfate; Inflammation; Colitis; Colonic Neoplasms; Colorectal Neoplasms; Carcinogenesis; Cell Transformation, Neoplastic
PubMed: 37489647
DOI: 10.1002/cnr2.1863 -
The American Journal of Emergency... Sep 2023Succinylcholine and rocuronium are the most commonly utilized neuromuscular blocker agents (NMBAs) for rapid sequence intubation (RSI) in the emergency department (ED)....
BACKGROUND
Succinylcholine and rocuronium are the most commonly utilized neuromuscular blocker agents (NMBAs) for rapid sequence intubation (RSI) in the emergency department (ED). The duration of action of rocuronium is significantly longer (∼30 min) compared to succinylcholine (∼10 min) and previous studies have shown that patients receiving rocuronium are more likely to have longer time to sedation initiation following RSI. Furthermore, patients receiving rocuronium may be more likely to experience awareness with paralysis than those receiving succinylcholine. The primary goal for this study was to evaluate the association between NMBA use during RSI and post-intubation sedation and analgesia practices in the ED.
METHODS
This was a retrospective, multicenter cohort study including patients 18 years and older that received succinylcholine or rocuronium during RSI in the ED between September 1, 2020 and August 31, 2021. Patients were excluded if they were intubated prior to ED arrival, experienced an out-of-hospital or in ED cardiac arrest, or received sugammadex within 60 min of rocuronium administration. Patients were screened in reverse chronological order until the targeted sample size was achieved and all data was abstracted from the electronic health record. The primary outcome was the time to initiation of analgesia or sedation. Secondary outcomes included dose of sedatives or analgesia administered at 30- and 60 min, and medications administered for post-intubation sedation or analgesia.
FINDINGS
A total of 200 ED patients were included of which 100 received succinylcholine and 100 received rocuronium. There was no difference in the median time to initiation of analgesia or sedation between the succinylcholine and rocuronium groups (10 vs 8.5 min, p = 0.82) or in Kaplan-Meier cumulative probabilities (p = 0.17). At 60 min post-RSI, those receiving succinylcholine received significantly higher median doses of propofol (20 μg/kg/min vs. 10 μg/kg/min; p = 0.02) and fentanyl [100 μg vs. 84.2 μg; p = 0.02].
CONCLUSION
While no differences were observed in the time to initiation of post-intubation sedation or analgesia in ED patients receiving succinylcholine compared to rocuronium, differences in the intensity of post-intubation regimens was observed. Further investigation is needed to evaluate the adequacy of sedation following RSI in the ED.
Topics: Humans; Succinylcholine; Rocuronium; Neuromuscular Depolarizing Agents; Retrospective Studies; Cohort Studies; Androstanols; Neuromuscular Nondepolarizing Agents; Intubation, Intratracheal; Analgesia; Emergency Service, Hospital
PubMed: 37356339
DOI: 10.1016/j.ajem.2023.06.017