Current perioperative nociception monitoring and potential directions.

Perioperative nociception-antinociception balance is essential for the prevention of adverse postoperative events. Estimating the nociception level helps optimize intraoperative management. In the past two decades, various nociception monitoring devices have been developed for the identification of intraoperative nociception. However, each type of nociception monitoring device has advantages and disadvantages, limiting their clinical application in particular patients and settings. Therefore, this review aimed to summarize the information on nociceptor monitoring in current clinical settings, explore each technique's particularities, and possible future directions to provide a reference for clinicians and researchers.

Transcriptomic and targeted metabolome analyses revealed the regulatory mechanisms of the synthesis of bioactive compounds in Citrus grandis 'tomentosa'.

Exocarpium Citri Grandis is a popular Chinese herbal medicine prepared from Citrus grandis 'tomentosa', and it is rich in several bioactive compounds, including flavonoids, coumarins, and volatile oils. However, studies are yet to elucidate the mechanisms of synthesis and regulation of these active components. Therefore, the present study examined the profiles of flavonoids and volatile oil bioactive compounds in plant petals, fruits, and tender leaves, and then performed RNA sequencing on different tissues to identify putative genes involved in the synthesis of bioactive compounds. The results show that the naringin, naringenin, and coumarin contents of the fruitlets were significantly higher than those of the tender leaves and petals, whereas the tender leaves had significantly higher levels of rhoifolin and apigenin. A total of 49 volatile oils, of which 10 were mainly found in flowers, 15 were mainly found in fruits, and 18 were mainly found in leaves, were identified. RNA sequencing identified 9,942 genes that were differentially expressed in different tissues. Further analysis showed that 20, 15, and 74 differentially expressed genes were involved in regulating flavonoid synthesis, regulating coumarin synthesis, and synthesis and regulation of terpenoids, respectively. CHI1 (Cg7g005600) and 1,2Rhat gene (Cg1g023820) may be involved in the regulation of naringin synthesis in C. grandis fruits. The HDR (Cg8g006150) gene, HMGS gene (Cg5g009630) and GGPS (Cg1g003650) may be involved in the regulation and synthesis of volatile oils in C. grandis petals. Overall, the findings of the present study enhance our understanding of the regulatory mechanisms of secondary metabolites in C. grandis, which could promote the breeding of C. grandis with desired characteristics.

Tuning microscopic structure of La-MOFs via ligand engineering effect towards enhancing phosphate adsorption.

The selection of different organic ligands when synthesizing metal organic framework (MOFs) can change their effects on the adsorption performance. Here, four La-MOFs adsorbents (La-SA, La-FA, La-TA and La-OA) with different organic ligands and structures were synthesized by solvothermal method for phosphate adsorption, and the relationship between their adsorption properties and structures was established. Among four La-MOFs, their phosphate adsorption capacities and adsorption rates followed La-SA > La-FA > La-TA > La-OA. The results indicated that average pore diameter played a key role in phosphate adsorption and there was a positive correlation between average pore diameter and adsorption capacity (R2 = 0.86). Coexisting ion experiments showed that phosphate adsorptions on three La-MOFs (La-SA, La-FA and La-TA) were inhibited in the presence of CO32- and HCO3-. The inhibition of CO32- was the most pronounced and the results of redundancy analysis pointed out that it was mainly due to the change of pH value. In contrast, La-OA showed enhanced phosphate adsorption in the presence of CO32- and HCO3-, and the combination of pH experiments showed that phosphate adsorption by La-OA was increased under alkaline conditions. Further combined with FT-IR, XRD, high resolution energy spectra of XPS (La 3d, P 2p and O 1s) and XANES, the adsorption mechanisms were derived electrostatic attraction, chemical precipitation and inner sphere complexation, and the last two were identified as the main mechanisms. Moreover, it can be identified from XPS 2p that the phosphate adsorption on La-FA and La-OA were mainly in the LaPO4 state, while La-SA and La-TA mainly existed in the form of LaPO4·xH2O crystals and inner sphere complexes. From the perspective of material morphology, this work provides a thought for the rational design of MOFs with adjustable properties for phosphate adsorption.

Hypoxia-triggered O-GlcNAcylation in the brain drives the glutamate-glutamine cycle and reduces sensitivity to sevoflurane in mice.

BACKGROUND: Hypersensitivity to general anaesthetics predicts adverse postoperative outcomes in patients. Hypoxia exerts extensive pathophysiological effects on the brain; however, whether hypoxia influences sevoflurane sensitivity and its underlying mechanisms remain poorly understood. METHODS: Mice were acclimated to hypoxia (oxygen 10% for 8 h day-1) for 28 days and anaesthetised with sevoflurane; the effective concentrations for 50% of the animals (EC50) showing loss of righting reflex (LORR) and loss of tail-pinch withdrawal response (LTWR) were determined. Positron emission tomography-computed tomography, O-glycoproteomics, seahorse analysis, carbon-13 tracing, site-specific mutagenesis, and electrophysiological techniques were performed to explore the underlying mechanisms. RESULTS: Compared with the control group, the hypoxia-acclimated mice required higher concentrations of sevoflurane to present LORR and LTWR (EC50LORR: 1.61 [0.03]% vs 1.46 [0.04]%, P<0.01; EC50LTWR: 2.46 [0.14]% vs 2.22 [0.06]%, P<0.01). Hypoxia-induced reduction in sevoflurane sensitivity was correlated with elevation of protein O-linked N-acetylglucosamine (O-GlcNAc) modification in brain, especially in the thalamus, and could be abolished by 6-diazo-5-oxo-l-norleucine, a glutamine fructose-6-phosphate amidotransferase inhibitor, and mimicked by thiamet-G, a selective O-GlcNAcase inhibitor. Mechanistically, O-GlcNAcylation drives de novo synthesis of glutamine from glucose in astrocytes and promotes the glutamate-glutamine cycle, partially via glycolytic flux and activation of glutamine synthetase. CONCLUSIONS: Intermittent hypoxia exposure decreased mouse sensitivity to sevoflurane anaesthesia through enhanced O-GlcNAc-dependent modulation of the glutamate-glutamine cycle in the brain.

Integrated metabolomics revealed the fibromyalgia-alleviation effect of Mo2C nanozyme through regulated homeostasis of oxidative stress and energy metabolism.

Fibromyalgia (FM), the most common cause of chronic musculoskeletal pain in the general public, lacks advanced therapeutic methodology and detailed bioinformation. However, acting as a newly developed and important transition metal carbide or carbonitride, the Mo2C nanozyme has provided a novel iatrotechnique with excellent bioactivity in a cell/animal model, which also exhibits potential prospects for future clinical applications. In addition, high-content and high-throughput integrated metabolomics (including aqueous metabolomics, lipidomics, and desorption electrospray ionization-mass spectrometry imaging) also specializes in qualitative and quantitative analysis of metabolic shifts at the molecular level. In this work, the FM-alleviation effect of Mo2C nanozyme was investigated through integrated metabolomics in a mouse model. An advanced platform combining gas chromatography-mass spectrometry, liquid chromatography-mass spectrometry and bioinformatics was utilized to study the variation in the mouse metabolome and lipidome. The results revealed that Mo2C treatment could effectively enhance energy metabolism-related biological events impaired by FM, leading to homeostasis of oxidative stress and energy metabolism toward the control levels. During this process, Mo2C facilitated the elimination of ROS in plasma and cells and the rehabilitation of mice from oxidative stress and mitochondrial dysfunction. It was believed that such an integrated metabolomics study on the FM-alleviation effect of Mo2C nanozyme could provide another excellent alternative to traditional Mo2C-based research with numerous pieces of bioinformation, further supporting research area innovation, material modification, and clinical application.

Phosphate removal and recovery by lanthanum-based adsorbents: A review for current advances.

Controlling eutrophication and recovering phosphate from water bodies are hot issues in the 21st century. Adsorption is considered to be the best method for phosphate removal because of its high adsorption efficiency and fast removal rate. Among the many adsorbents, lanthanum (La)-based adsorbents have been paid more and more attention due to their strong affinity to phosphorus. This paper reviews research of phosphate adsorption on La-based adsorbents in different La forms, including lanthanum oxide/hydroxide, lanthanum mixed metal oxide/hydroxide, lanthanum carbonate, La3+, La-based metal-organic framework (La-MOF) and La-MOF derivatives. The La-based adsorbents can be loaded on many carriers, such as carbon material, clay minerals, porous silica, polymers, industrial wastes, and others. We find that lanthanum oxide/hydroxide and La3+ adsorbents are mostly studied, while those in the forms of lanthanum carbonate, La-MOF, and La-MOF derivatives are relatively few. The kinetic process of most phosphate adsorption is pseudo-second-order and the isotherm process is in accordance with the Langmuir model. The cost of La-based and other traditional adsorbents was compared. The adsorption mechanisms are categorized as electrostatic attraction, ligand exchange, Lewis acid-base interaction, ion exchange and surface precipitation. Besides, regeneration methods of La-based adsorbents are mainly acid, alkali, and salt-alkali. In addition, the La-based adsorbents after absorbing phosphate can be directly used as a slow-release fertilizer. This review provides a basis for the research on phosphate adsorption by La-based adsorbents. It should be carried out to further develop La-based materials with high adsorption capacity and good regeneration ability. Meanwhile, studies have been conducted on the reuse of phosphate after desorption, which needs more attention in future research.

Ketone Body ß-Hydroxybutyrate Prevents Myocardial Oxidative Stress in Septic Cardiomyopathy.

Septic cardiomyopathy is a life-threatening complication of severe sepsis and septic shock. Oxidative stress and mitochondrial dysfunction have been identified as significant abnormalities in septic cardiomyopathy. However, specific treatments are rare. This study aims to investigate the impact of ß-hydroxybutyrate (ß-OHB) on septic cardiomyopathy and explore the underlying mechanism(s). We found that pretreatment of D-ß-hydroxybutyrate-(R)-1,3 butanediol monoester (ketone ester, 3 mg/g body weight, once daily) by gavage for three days elevated the levels of ketone bodies, especially that of ß-hydroxybutyrate (ß-OHB) in the circulation and mouse hearts, which exerted a protective effect against lipopolysaccharide (LPS, 20 mg/kg)-induced septic cardiomyopathy in mice. In addition, an LPS-stimulated macrophage-conditioned medium (MCM) was used to mimic the pathological process of septic cardiomyopathy. Mechanistically, ß-OHB alleviated myocardial oxidative stress and improved mitochondrial respiratory function through the antioxidant FoxO3a/MT2 pathway activated via histone deacetylase (HDAC) inhibition, which ultimately enhanced heart performance in septic cardiomyopathy. Our results, therefore, suggested an unappreciated critical role of ß-OHB in septic heart protection as well as highlighted the potential of ß-OHB as a simple remedy for the septic cardiomyopathy population.

Chronic Alcohol Intake Exacerbates Cardiac Dysfunction After Myocardial Infarction.

AIMS: Alcohol intake is a risk factor for cardiovascular diseases. This study was designed to investigate whether chronic alcohol intake affects myocardial infarction (MI)-induced cardiac remodeling and heart failure. METHODS: Eight-week-old male C57BL/6 mice were randomly divided into four groups: Sham group (Sham), MI plus drinking water group (MI + Vehicle), and MI plus daily alcohol intake for 6 weeks with or without gavage of additional alcohol every 3 days (MI + Alcohol and MI + Alcohol + G). The MI were induced by permanent left anterior descending (LAD) coronary artery ligation surgery before vehicle or alcohol treatment. The blood alcohol concentration (BAC), cardiac function, release of cardiac enzymes, pathological changes and mitochondrial function were measured. RESULTS: As expected, supplementation of alcohol in drinking water significantly increased random BAC in mice. Long-term exposure to alcohol further reduced body weight, ejection fraction and fractional shortening in comparison with the MI + Vehicle group. Histopathological data showed that alcohol increased fibrosis in infarct zone, which was well correlated with the functional decline. Also, as compared to the MI + Vehicle group, the adenosine diphosphate-supported respiratory function of freshly isolated cardiac mitochondria was inhibited in the MI + Alcohol + G group. Besides, upon MI-induced cardiac damage, we did not observe further changes in heart weight, cardiomyocyte enlargement in remote zone, exercise capacity, lung edema and the release of cardiac enzyme after chronic alcohol intake. CONCLUSIONS: Our study demonstrated that chronic daily alcohol exposure exacerbated MI-induced cardiac dysfunction, which is related to promoted myocardial fibrosis and inhibited mitochondrial function.

MicroRNA-127 targeting of mitoNEET inhibits neurite outgrowth, induces cell apoptosis and contributes to physiological dysfunction after spinal cord transection.

Neuroregeneration and apoptosis are two important pathophysiologic changes after spinal cord injury (SCI), but their underlying mechanisms remain unclear. MicroRNAs (miRNAs) play a crucial role in the regulation of neuroregeneration and neuronal apoptosis, research areas that have been greatly expanded in recent years. Here, using miRNA arrays to profile miRNA transcriptomes, we demonstrated that miR-127-3p was significantly down-regulated after spinal cord transection (SCT). Then, bioinformatics analyses and experimental detection showed that miR-127-3p exhibited specific effects on the regulation of neurite outgrowth and the induction of neuronal apoptosis by regulating the expression of the mitochondrial membrane protein mitoNEET. Moreover, knockdown of MitoNEET leaded to neuronal loss and apoptosis in primary cultured spinal neurons. This study therefore revealed that miR-127-3p, which targets mitoNEET, plays a vital role in regulating neurite outgrowth and neuronal apoptosis after SCT. Thus, modificatioin of the mitoNEET expression, such as mitoNEET activition may provide a new strategy for the treatment of SCI in preclinical trials.

Transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) improves brain ischemia-induced pulmonary injury in rats associated to TNF-α expression.

BACKGROUND: Bone marrow mesenchymal stem cell (BMSCs)-based therapy seems to be a promising treatment for acute lung injury, but the therapeutic effects of BMSCs transplantation on acute lung injury induced by brain ischemia and the mechanisms have not been totally elucidated. This study explores the effects of transplantation of BMSCs on acute lung injury induced by focal cerebral ischemia and investigates the underlying mechanism. METHODS: Acute lung injury model was induced by middle cerebral artery occlusion (MCAO). BMSCs (with concentration of 1 × 10(6)/ml) were transplanted into host through tail vein 1 day after MCAO. Then, the survival, proliferation and migration of BMSCs in lung were observed at 4 days after transplantation, and histology observation and lung function were assessed for 7 days. Meanwhile, in situ hybridization (ISH), qRT-PCR and western blotting were employed to detect the expression of TNF-α in lung. RESULTS: Neurobehavioral deficits and acute lung injury could be seen in brain ischemia rats. Implanted BMSCs could survive in the lung, and relieve pulmonary edema, improve lung function, as well as down regulate TNF-α expression. CONCLUSIONS: The grafted BMSCs can survive and migrate widespread in lung and ameliorate lung injury induced by focal cerebral ischemia in the MCAO rat models. The underlying molecular mechanism, at least partially, is related to the suppression of TNF-α.

Role of endogenous PDGF-BB in cultured cardiomyocytes exposed to hypoxia.

Platelet-derived growth factor-BB (PDGF-BB) plays a critical role in cell proliferation, angiogenesis and fibrosis. However, its exact role in cardiomyocytes exposed to hypoxia is not well known. This study was therefore designed to detect whether PDGF-BB expression was changed in a hypoxic condition, then the possible role of endogenous PDGF-BB in cardiomyocytes was explored, with interference RNA in a lentiviral vector ex vivo. The results showed that cultured cardiomyocytes exhibited an optimal proliferation from 3 to 10 days. However, LDH level was significantly increased but the heart rhythm was not altered in cardiomyocytes exposed to hypoxia for 24 hours. PDGF-BB expression was substantially upregulated in hypoxic cardiomyocytes. In order to know the role of PDGF-BB, we performed PDGF-BB knockdown in cultured cardiomyocytes. The number of apoptotic cells and the level of LDH were significantly increased but the beat rhythm was reduced in cardiomyocytes with PDGF-BB knockdown. These findings suggest that endogenous PDGF-BB exerts a crucial protective effect to cultured cardiomyocytes exposed to hypoxia.