Construction and analysis of a network of exercise-induced mitochondria-related non-coding RNA in the regulation of diabetic cardiomyopathy.

Diabetic cardiomyopathy (DCM) is a major factor in the development of heart failure. Mitochondria play a crucial role in regulating insulin resistance, oxidative stress, and inflammation, which affect the progression of DCM. Regular exercise can induce altered non-coding RNA (ncRNA) expression, which subsequently affects gene expression and protein function. The mechanism of exercise-induced mitochondrial-related non-coding RNA network in the regulation of DCM remains unclear. This study seeks to construct an innovative exercise-induced mitochondrial-related ncRNA network. Bioinformatic analysis of RNA sequencing data from an exercise rat model identified 144 differentially expressed long non-coding RNA (lncRNA) with cutoff criteria of p< 0.05 and fold change ≥1.0. GSE6880 and GSE4745 were the differentially expressed mRNAs from the left ventricle of DCM rat that downloaded from the GEO database. Combined with the differentially expressed mRNA and MitoCarta 3.0 dataset, the mitochondrial located gene Pdk4 was identified as a target gene. The miRNA prediction analysis using miRanda and TargetScan confirmed that 5 miRNAs have potential to interact with the 144 lncRNA. The novel lncRNA-miRNA-Pdk4 network was constructed for the first time. According to the functional protein association network, the newly created exercise-induced ncRNA network may serve as a promising diagnostic marker and therapeutic target, providing a fresh perspective to understand the molecular mechanism of different exercise types for the prevention and treatment of diabetic cardiomyopathy.

Improved cardioprotective effect of 3-nitro-N-methyl salicylamide solution after a prolonged preservation time of rat heart.

Ischemic reperfusion injury, caused by oxidative stress during reperfusion, is an inevitable outcome of organ transplantation, especially when the organ preservation time is prolonged. Prolonged ischaemic preservation is a valuable technique for improving the success of organ transplantation, but numerous challenges remain. 3-nitro-N-methyl salicylamide (3-NNMS), an inhibitor of mitochondrial electron transport chain complex III, can be used to reduce reactive oxygen species production during blood reperfusion by slowing the electron flow rate of the respiratory chain. Based on this property, a novel preservation solution was developed for the preservation of isolated rat heart and its cardioprotective effect was investigated during an 8-h cold ischaemia preservation time for the first time. For comparison, 3-NNMS was also included in the histidine-tryptophan-ketoglutarate (HTK) solution. Compared to HTK, HTK supplemented with 3-NNMS significantly improved the heart rate of isolated rat hearts after 8 h of cold storage. Both 3-NNMS solution and HTK supplemented with 3-NNMS solution decreased cardiac troponin T and lactate dehydrogenase levels in perfusion fluid and reduced reactive oxygen species and malondialdehyde levels in the myocardium. The 3-NNMS also maintained the membrane potential of myocardial mitochondria and significantly increased superoxide dismutase levels. These results showed that the new 3-NNMS solution can protect mitochondrial and cardiomyocyte function by increasing antioxidant capacity and reducing oxidative stress in cryopreserved rat hearts during a prolonged preservation time, resulting in less myocardial injury and better heart rate.

Occurrence Modes of AAEMs (Na+ and Ca2+) and the Effect on the Molecular Structures of Zhundong Coal via Quantum Chemistry.

Zhundong coal is known for its high content of alkali and alkaline earth metals (AAEMs), which greatly influences coal processing and utilization. To reveal the occurrence modes and the effect of AAEM ions on the molecular structures of Zhundong coal, the previously constructed molecular structure models of vitrinite-rich and inertinite-rich Zhundong coal (ZD-V and ZD-I) were selected to simulate using quantum chemical methods. By focusing on Na+ and Ca2+, the adsorption capacity at different adsorption sites was investigated based on the density functional theory (DFT), and the effects of adsorption of Na+ and Ca2+ on nearby atomic charges, chemical bonds, and molecular orbitals were investigated. Results show that compared with ZD-I, ZD-V contains a more negative electrostatic potential (ESP) distribution and lower bond order, indicating that vitrinite contains more adsorption sites for AAEM ions and exhibits stronger chemical reactivity. Na+ and Ca2+ are easily adsorbed to the most negative ESP with the optimal adsorption site near the carbonyl group (C=O). Compared with adsorbed Na+, Ca2+ has a smaller adsorption distance from the molecule and a higher adsorption energy. Ca2+ can transfer more charge than Na+ and has more affinity with the coal molecule. Ca2+ at all adsorption sites is bound to organic molecules by chemisorption, which also reveals the reason for the low water-soluble Ca content in coal at the molecular level. Adsorption of AAEM ions has a more significant effect on the chemical bond of oxygen-containing functional groups near AAEM ions compared to the overall molecular fragments, which makes the nearby chemical bonds (C-O/C=O) decrease in bond order and increase in bond length. Ca2+ makes the nearby chemical bonds more prone to break than Na+. Additionally, Ca2+ has a more significant impact on the energy gaps (ΔEgap) compared to Na+. Adsorption of Ca2+ near the carbonyl and carboxyl groups leads to a significant decrease in ΔEgap, indicating an enhanced chemical reactivity of coal molecular fragments.

miR­27a­3p upregulation by p65 facilitates cervical tumorigenesis by increasing TAB3 expression and is involved in the positive feedback loop of NF­κB signaling.

An altered microRNA (miRNA/miR)­27a­3p expression has been identified in cervical cancer, while the exact regulatory mechanisms responsible for the dysregulation of miR­27a­3p remain to be fully elucidated. In the present study, a NF­κB/p65 binding site was identified upstream of the miR­23a/27a/24­2 cluster and p65 binding enhanced the transcription of pri­miR­23a/27a/24­2, as well as the expression levels of mature miRNAs, including miR­27a­3p in HeLa cells. Mechanistically, using bioinformatics analyses and experimental validation, TGF­ß activated kinase 1 binding protein 3 (TAB3) was identified as a direct target of miR­27a­3p. By binding to the 3'UTR of TAB3, miR­27a­3p significantly enhanced TAB3 expression. Functionally, it was found that the overexpression of miR­27a­3p and TAB3 promoted the malignant potential of cervical cancer cells, as evaluated using cell growth, migration and invasion assays, and specific cell marker determinations in the epithelial mesenchymal transition progression, and vice versa. Further rescue experiments revealed that the enhanced malignant effects induced by miR­27a­3p were mediated via its upregulation of TAB3 expression. Moreover, miR­27a­3p and TAB3 also activated the NF­κB signaling pathway and formed a positive feedback regulatory loop composing of p65/miR­27a­3p/TAB3/NF­κB. On the whole, the findings presented herein may provide novel insight into the underlying cervical tumorigenesis and novel biomarker identification for clinical applications.

Occurrence Modes of Critical Metals (Li+ and Ge4+) in the Organic Molecular Structures of Coal: A Density Functional Theory Study.

To explore the mechanism of critical metal (Li+ and Ge4+) occurrence in the organic molecular structures of different rank coals, simulations were investigated using quantum chemical density functional theory. In this paper, Wender lignite, bituminous, and anthracite molecular models were used as organic molecular structures in coal. The electrostatic potential (ESP), frontier molecular orbitals, and Mulliken charges were used to identify adsorption sites in organic molecular structures. Mulliken charge, bond length, Mayer bond order (MBO), and adsorption energy values were used to estimate the binding conformation and strength between organic molecular structures and critical metals (Li+ and Ge4+). The results showed that the negative ESP, the highest occupied molecular orbitals, and negative Mulliken charges in the organic molecular structures were located at the O atom of oxygen functional groups and the aromatic structures, respectively, which were the active sites for critical metal adsorption. Mulliken charge transfer, bond length, MBO, and adsorption energy data suggested that the binding of Li+ with organic molecular structures was controlled by the carbonyl group (C=O), while the aromatic structures had less effect on the occurrence of Li+ in the organic molecular structures. The maximum adsorption energy value for binding Li+ with organic molecular structures was -742.16 kJ/mol. The Ge4+ ions not only showed strong binding ability with oxygen functional groups, but also Ge4+ formed thermodynamically stable half-sandwich complexes with aromatic structures. Therefore, the coal rank had little effect on the binding of Ge4+ with organic molecular structures. Moreover, the binding of Ge4+ with organic molecule structures was enhanced by the synergistic interactions of oxygen functional groups and aromatic structures. The adsorption energy values were up to -8511.43 kJ/mol. The adsorption of organic matter in coal to critical metals (Li+ and Ge4+) generated changes in the spatial configuration of the organic molecular structure, including local twisting of the organic molecular structure in lignite and bending of the aromatic structure in anthracite.

Construction and verification of vitrinite-rich and inertinite-rich Zhundong coal models at the aggregate level: new insights from the spatial arrangement and thermal behavior perspective.

To explore the thermal behavior of Zhundong coal from the perspective of maceral, it is essential to conduct molecular simulations based on constructing a realistic aggregate model of coal. Here, two Zhundong coal samples ZD-V (vitrinite-rich) and ZD-I (inertinite-rich) were collected, and coal models were constructed using elemental analysis, solid-state 13C-nuclear magnetic resonance (13C-NMR), X-ray photoelectron spectroscopy (XPS), and Fourier transform infrared spectrometry (FTIR). The chemical formulas of 2D vitrinite-rich coal and inertinite-rich coal constructed are C152H167NO36 and C155H119NO28, respectively. The chemical structure information matches well with that determined by those analysis results, including elemental analysis, structural composition, and 13C-NMR spectra. The final aggregate models show that the dimension of the unit cell is 2.785 × 2.785 × 2.785 nm for ZD-V and 2.743 × 2.743 × 2.743 nm for ZD-I, including six macromolecules respectively. The final aggregate structure models were verified by comparing experiments and simulation results. In addition to the verification with He density, the spatial arrangement of the aggregate model was verified by simulated XRD spectrum. And moreover, the thermal behavior was verified by ReaxFF MD, and the simulated trend of thermal weight loss and cumulative total molecules released were consistent with TG-MS. The final models show the visual difference between ZD-V and ZD-I, whether the 2D molecular structure or aggregation state. ZD-V is dominated by chain hydrocarbons, while ZD-I is dominated by cyclic hydrocarbons with linked aromatic rings. The aromatic substitution of oxygen atoms is different, ZD-V is mainly composed of ortho-disubstituted arenes, and ZD-I is mainly composed of meta-disubstituted arenes. In addition, ZD-V has a lower ultra-micropore size distribution and porosity than ZD-I. This study presents a comprehensive approach to construct and verify aggregate models from the spatial arrangement and thermal behavior perspective, and the constructed Zhundong coal models can provide a foundation for further exploration of the thermal reactivity (e.g. combustion, liquefaction, etc.) of coal from maceral aspects.

Objective inversion of the continuous atmospheric 137Cs release following the Fukushima accident.

Eleven years after the Fukushima accident, independent objective estimates of the atmospheric 137Cs release still suffer from discontinuities such as negative release terms, oscillations, and temporal gaps, leading to noticeable differences from the subjective estimate. This paper describes an objective method that handles these artifacts and promotes the continuity of releases at fine resolutions. The proposed method uses the joint estimation model to reduce the oscillations induced by the model-observation discrepancies, and employs total variation regularization to recover the missing releases caused by insufficient observations. Adaptive parameterization is used to correct negative values. The application of this method to the Fukushima accident produces a source term that accurately approximates continuous releases at a fine temporal resolution of 1 h, providing a better match with the recognized subjective source term than nine published estimates, with a Pearson's correlation coefficient of 0.923 and an index of agreement of 0.872. This source term agrees with the timing of on-site gamma dose rate peaks, significantly improving the air concentration and deposition simulations, with FAC10 values of 0.564 and 0.990, respectively. The estimation error varies smoothly in a limited range with different regularization parameters, enabling automatic parameterization and demonstrating the potential for operational inversions.

Efficiency calibration and self-attenuation correction in radioxenon measurement using ß-γ coincidence method.

Measurement of the four radioxenon isotopes, namely 131mXe, 133mXe, 133Xe, and 135Xe, play a key role in underground nuclear test monitoring for ensuring compliance with the Comprehensive Nuclear-Test-Ban Treaty (CTBT). To improve detection sensitivity, a ß-γ coincidence technique is commonly used. Due to the presence of the gas matrix, such as stable xenon, nitrogen, helium, the self-attenuation effects should be taken into account when measuring different types of sample. In order to improve the accuracy of the measurement, the detection efficiencies of X-rays and γ-rays were derived by using a simulation gas calibration source with low density of sponge matrix. The detection efficiencies of ß-particles and conversion electrons (CEs) were calibrated by measuring radioxenon sample. The self-attenuation correction factors of X-rays and γ-rays were determined by Geant4 simulation method. The self-attenuation correction factors of ß-particles and CEs were provided by measuring the radioxenon samples with different volumes of xenon, nitrogen and helium.

Inversion of 137Cs emissions following the fukushima accident with adaptive release recovery for temporal absences of observations.

Temporal absences in observation records lead to release losses during the source term inversions of atmospheric radionuclide emissions. Consequently, objectively-estimated source terms for the Fukushima accident contain fewer release details and present large discrepancies when compared with the expert-judged one. This paper describes an objective method that can adaptively recover the missing releases caused by the temporal absences of observations. The proposed method assumes that the accident releases of radionuclides are piecewise-constant and comprise both peaks and constant releases. The missing releases are adaptively recovered as either peaks or constant releases by minimizing the total variation of the estimated source term. The proposed method is applied to the Fukushima accident and evaluated against regional airborne and deposited 137Cs observations. The results demonstrate that this method effectively recovers the missing releases, producing a source term that matches the timing of both on-site gamma dose rate peaks and accident events. The retrieved source term improves the simulation of air concentrations and reproduces most of the deposition patterns. This is the first time that an objective method has independently reproduced the details in the expert-judged one for the Fukushima accident.

IP3R1/GRP75/VDAC1 complex mediates endoplasmic reticulum stress-mitochondrial oxidative stress in diabetic atrial remodeling.

RATIONALE: Endoplasmic reticulum (ER) stress and mitochondrial dysfunction are important mechanisms of atrial remodeling, predisposing to the development of atrial fibrillation (AF) in type 2 diabetes mellitus (T2DM). However, the molecular mechanisms underlying these processes especially their interactions have not been fully elucidated. OBJECTIVE: To explore the potential role of ER stress-mitochondrial oxidative stress in atrial remodeling and AF induction in diabetes. METHODS AND RESULTS: Mouse atrial cardiomyocytes (HL-1 cells) and rats with T2DM were used as study models. Significant ER stress was observed in the diabetic rat atria. After treatment with tunicamycin (TM), an ER stress agonist, mass spectrometry (MS) identified several known ER stress and calmodulin proteins, including heat shock protein family A (HSP70) member [HSPA] 5 [GRP78]) and HSPA9 (GRP75, glucose-regulated protein 75). In situ proximity ligation assay indicated that TM led to increased protein expression of the IP3R1-GRP75-VDAC1 (inositol 1,4,5-trisphosphate receptor 1-glucose-regulated protein 75-voltage-dependent anion channel 1) complex in HL-1 cells. Small interfering RNA silencing of GRP75 in HL-1 cells and GRP75 conditional knockout in a mouse model led to impaired calcium transport from the ER to the mitochondria and alleviated mitochondrial oxidative stress and calcium overload. Moreover, GRP75 deficiency attenuated atrial remodeling and AF progression in Myh6-Cre+/Hspa9flox/flox + TM mice. CONCLUSIONS: The IP3R1-GRP75-VDAC1 complex mediates ER stress-mitochondrial oxidative stress and plays an important role in diabetic atrial remodeling.

Radioactivity measurement of 85Kr by using anti-cosmic HPGe γ spectrometer.

In order to improve the detection sensitivity of 85Kr, an anti-cosmic HPGe γ spectrometer was established and a specific Marinelli beaker was designed for 85Kr measurement. Comparing to the non-anticoincidence γ spectrum, the integral background counts rate range from 20 to 2400 keV was reduced by a factor of 5.17 using anticoincidence shielding. The minimum detectable activity of 85Kr was 10.5 Bq within 24 h measurement in standard mode and that of 3.99 Bq in anticoincidence mode. The activity concentration of atmospheric 85Kr was preliminarily measured to be an average of 1.30 Bq/m3 in Beijing and corresponding minimum detectable concentration was 0.2 Bq/m3.

Pioglitazone Inhibits Diabetes-Induced Atrial Mitochondrial Oxidative Stress and Improves Mitochondrial Biogenesis, Dynamics, and Function Through the PPAR-γ/PGC-1α Signaling Pathway.

Background: Oxidative stress contributes to adverse atrial remodeling in diabetes mellitus. This remodeling can be prevented by the PPAR-γ agonist pioglitazone via its antioxidant and anti-inflammatory effects. In this study, we examined the molecular mechanisms underlying the protective effects of pioglitazone on atrial remodeling in a rabbit model of diabetes. Methods: Rabbits were randomly divided into control, diabetic, and pioglitazone-treated diabetic groups. Echocardiographic, hemodynamic, and electrophysiological parameters were measured. Serum PPAR-γ levels, serum and tissue oxidative stress and inflammatory markers, mitochondrial morphology, reactive oxygen species (ROS) production rate, respiratory function, and mitochondrial membrane potential (MMP) levels were measured. Protein expression of the pro-fibrotic marker TGF-ß1, the PPAR-γ coactivator-1α (PGC-1α), and the mitochondrial proteins (biogenesis-, fusion-, and fission-related proteins) was measured. HL-1 cells were transfected with PGC-1α small interfering RNA (siRNA) to determine the underlying mechanisms of pioglitazone improvement of mitochondrial function under oxidative stress. Results: The diabetic group demonstrated a larger left atrial diameter and fibrosis area than the controls, which were associated with a higher incidence of inducible atrial fibrillation (AF). The lower serum PPAR-γ level was associated with lower PGC-1α and higher NF-κB and TGF-ß1 expression. Lower mitochondrial biogenesis (PGC-1α, NRF1, and TFAM)-, fusion (Opa1 and Mfn1)-, and fission (Drp1)-related proteins were detected. Mitochondrial swelling, higher mitochondrial ROS, lower respiratory control rate, and lower MMP were observed. The pioglitazone group showed a reversal of structural remodeling and a lower incidence of inducible AF, which were associated with higher PPAR-γ and PGC-1α. The pioglitazone group had lower NF-κB and TGF-ß1 expression levels, whereas biogenesis-, fusion-, and fission-related protein expression was higher. Further, mitochondrial structure and function were improved. In HL-1 cells, PGC-1α siRNA transfection blunted the effect of pioglitazone on Mn-SOD protein expression and MMP collapse in H2O2-treated cells. Conclusion: Diabetes mellitus induces adverse atrial structural, electrophysiological remodeling, and mitochondrial damage and dysfunction. Pioglitazone prevented these abnormalities through the PPAR-γ/PGC-1α pathway.

Assessment of a compton-suppressed spectrometer for measurement of radioactive xenon isotopes.

Airborne radionuclide monitoring is considered to be the most certain way to detect a clandestine nuclear weapon test. The activity concentration of radioxenon samples collected by the radionuclide stations of the International Monitoring System (IMS) for the Comprehensive Nuclear-Test-Ban Treaty (CTBT) is generally performed at the low-level, hence it is necessary to improve the detection sensitivity of the radioactivity measuring apparatus for radionuclide monitoring. The Compton-suppressed spectrometer (CSS) has the advantage of reducing the background and improving the sensitivity in the environmental level measurement. Therefore, the measurement of the relevant radioxenon sample at the environmental level is feasible by using CSS. To assess the performance of CSS for radioxenon measurements, the Compton-suppressed and unsuppressed spectra of the 133Xe and 127Xe samples have been acquired, and subsequently, the information of the full energy peaks (FEP) in the spectra were compared. The assessment indicates that CSS can provide high sensitivity, simple operation, and straightforward activity determination, and it can be regarded as an appropriate apparatus in the radioxenon measurement.

Hyperglycemia Induces Endoplasmic Reticulum Stress in Atrial Cardiomyocytes, and Mitofusin-2 Downregulation Prevents Mitochondrial Dysfunction and Subsequent Cell Death.

Mitochondrial oxidative stress and dysfunction play an important role of atrial remodeling and atrial fibrillation (AF) in diabetes mellitus. Endoplasmic reticulum (ER) stress has been linked to both physiological and pathological states including diabetes. The aim of this project is to explore the roles of ER stress in hyperglycemia-induced mitochondrial dysfunction and cell death of atrial cardiomyocytes. High glucose upregulated ER stress, mitochondrial oxidative stress, and mitochondria-associated ER membrane (MAM)- enriched proteins (such as glucose-regulated protein 75 (GRP75) and mitofusin-2 (Mfn2)) of primary cardiomyocytes in vitro. Sodium phenylbutyrate (4-PBA) prevented the above changes. Silencing of Mfn2 in HL-1 cells decreased the Ca2+ transfer from ER to mitochondria under ER stress conditions, which were induced by the ER stress agonist, tunicamycin (TM). Electron microscopy data suggested that Mfn2 siRNA significantly disrupted ER-mitochondria tethering in ER stress-injured HL-1 cells. Mfn2 silencing attenuated mitochondrial oxidative stress and Ca2+ overload, increased mitochondrial membrane potential and mitochondrial oxygen consumption, and protected cells from TM-induced apoptosis. In summary, Mfn2 plays an important role in high glucose-induced ER stress in atrial cardiomyocytes, and Mfn2 silencing prevents mitochondrial Ca2+ overload-mediated mitochondrial dysfunction, thereby decreasing ER stress-mediated cardiomyocyte cell death.

OPA1 and MICOS Regulate mitochondrial crista dynamics and formation.

Mitochondrial cristae are the main site for oxidative phosphorylation, which is critical for cellular energy production. Upon different physiological or pathological stresses, mitochondrial cristae undergo remodeling to reprogram mitochondrial function. However, how mitochondrial cristae are formed, maintained, and remolded is still largely unknown due to the technical challenges of tracking mitochondrial crista dynamics in living cells. Here, using live-cell Hessian structured illumination microscopy combined with transmission electron microscopy, focused ion beam/scanning electron microscopy, and three-dimensional tomographic reconstruction, we show, in living cells, that mitochondrial cristae are highly dynamic and undergo morphological changes, including elongation, shortening, fusion, division, and detachment from the mitochondrial inner boundary membrane (IBM). In addition, we find that OPA1, Yme1L, MICOS, and Sam50, along with the newly identified crista regulator ATAD3A, control mitochondrial crista dynamics. Furthermore, we discover two new types of mitochondrial crista in dysfunctional mitochondria, "cut-through crista" and "spherical crista", which are formed due to incomplete mitochondrial fusion and dysfunction of the MICOS complex. Interestingly, cut-through crista can convert to "lamellar crista". Overall, we provide a direct link between mitochondrial crista formation and mitochondrial crista dynamics.

Wenxin Keli Regulates Mitochondrial Oxidative Stress and Homeostasis and Improves Atrial Remodeling in Diabetic Rats.

Mitochondrial dysfunction and oxidative stress play an important role in the pathogenesis of both atrial fibrillation (AF) and diabetes mellitus (DM). Wenxin Keli (WXKL), an antiarrhythmic traditional Chinese medicine, has been shown to prevent cardiac arrhythmias through modulation of cardiac ion channels. This study tested the hypothesis that WXKL can improve atrial remodeling in diabetic rats by restoring mitochondrial function. Primary atrial fibroblasts of neonatal SD rats were divided into four groups: control, hydrogen peroxide (H2O2), H2O2+WXKL 1 g/L, and H2O2+WXKL 3 g/L groups. Intracellular mitochondrial membrane potential (MMP), reactive oxygen species (ROS), and mitochondrial oxygen consumption were measured. SD male rats were randomly divided into three groups: control, DM, and DM+WXKL groups. Rats in the DM+WXKL group were treated with daily gavage of WXKL at 3 g/kg. After eight weeks, echocardiography, hemodynamic examination, histology, electrophysiology study, mitochondrial respiratory function, and western blots were assessed. H2O2 treatment led to increased ROS and decreased intracellular MMP and mitochondrial oxygen consumption in primary atrial fibroblasts. WXKL improved the above changes. DM rats showed increased atrial fibrosis, greater left atrial diameter, lower atrial conduction velocity, higher conduction heterogeneity, higher AF inducibility, and lower mitochondrial protein expression, and all these abnormal changes except for left atrial diameter were improved in the DM+WXKL group. WXKL improves atrial remodeling by regulating mitochondrial function and homeostasis and reducing mitochondrial ROS in diabetic rats.

Empagliflozin, a sodium glucose co-transporter-2 inhibitor, alleviates atrial remodeling and improves mitochondrial function in high-fat diet/streptozotocin-induced diabetic rats.

BACKGROUND: Diabetes mellitus is an important risk factor for atrial fibrillation (AF) development. Sodium-glucose co-transporter-2 (SGLT-2) inhibitors are used for the treatment of type 2 diabetes mellitus (T2DM). Their cardioprotective effects have been reported but whether they prevent AF in T2DM patients are less well-explored. We tested the hypothesis that the SGLT-2 inhibitor, empagliflozin, can prevent atrial remodeling in a diabetic rat model. METHODS: High-fat diet and low-dose streptozotocin (STZ) treatment were used to induce T2DM. A total of 96 rats were randomized into the following four groups: (i) control (ii) T2DM, (iii) low-dose empagliflozin (10 mg/kg/day)/T2DM; and (iv) high-dose empagliflozin (30 mg/kg/day)/T2DM by the intragastric route for 8 weeks. RESULTS: Compared with the control group, left atrial diameter, interstitial fibrosis and the incidence of AF inducibility were significantly increased in the DM group. Moreover, atrial mitochondrial respiratory function, mitochondrial membrane potential, and mitochondrial biogenesis were impaired. Empagliflozin treatment significantly prevented the development of these abnormalities in DM rats, likely via the peroxisome proliferator-activated receptor-c coactivator 1α (PGC-1α)/nuclear respiratory factor-1 (NRF-1)/mitochondrial transcription factor A (Tfam) signaling pathway. CONCLUSIONS: Empagliflozin can ameliorate atrial structural and electrical remodeling as well as improve mitochondrial function and mitochondrial biogenesis in T2DM, hence may be potentially used in the prevention of T2DM-related atrial fibrillation.

Plasma Metabolic Profiling Analysis of Gout Party on Acute Gout Arthritis Rats Based on UHPLC-Q-TOF/MS Combined with Multivariate Statistical Analysis.

Gout Party is a Chinese medicine prescription composed of Aconiti Lateralis Radix Praeparaia, Aconiti Radix Cocta, Cremastrae Pseudobulbus Pleiones Pseudobulbus, Smilacis Glabrae Rhizoma, Rehmanniae Radix, and Glycyrrhizae Radix et Rhizoma, which can relieve joint pain caused by gouty arthritis (GA) and rheumatoid, and has a therapeutic effect on acute gouty arthritis (AGA). However, little information is available on the molecular biological basis and therapeutic mechanism of Gout Party for the treatment of AGA. AGA model was established by injecting sodium urate, and colchicine served as a positive control drug. We established a metabolomic method based on ultra-high-performance liquid chromatography-tandem quadrupole/time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) to analyze the plasma samples of model group rats and blank group rats. Multiple statistical analyses, including principal component analysis (PCA) and partial least square discrimination analysis (PLS-DA), were used to examine metabolite profile changes in plasma samples. Finally, we identified 2-ketobutyric acid, 3-hexenedioic acid, but-2-enoic acid, and so on; 22 endogenous metabolites associated with AGA. After successful molding, we found that 2-ketobutyric acid, 3-hexenedioic acid, but-2-enoic acid, argininic acid, galactonic acid, lactic acid, equol 4'-O-glucuronide, deoxycholic acid glycine conjugate, glycocholic acid, sphinganine 1-phosphate, LPE (0:0/20:3), LPE (0:0/16:0), LPC (15:0) decreased significantly (p < 0.05 or p < 0.01), alanine, erythrulose, 3-dehydrocarnitine, m-methylhippuric acid, 3-hydroxyoctanoic acid, p-cresol sulfate, estriol 3-sulfate 16-glucuronide, 10-hydroxy-9-(phosphonooxy)octadecenoate, docosahexaenoic acid increased significantly (p < 0.05 or p < 0.01). After Gout Party treatment, 14 biomarkers had a tendency to normal conditions. These above biomarkers were mainly involved in fatty acid metabolism, bile acid metabolism, amino acid metabolism, and energy metabolism pathways. These results suggested that Gout Party exerted therapeutic effects of treating AGA by improving energy metabolism disorder and amino acid metabolism dysfunction, and attenuating fatty acid metabolism abnormal and inflammation. The results of this experiment provided a reference for revealing the metabolic mechanism produced by Gout Party in the treatment of AGA, but the subsequent studies need to be further improved and supported by relevant cell experiments and clinical experiments.

Measurement of the gamma-ray emission probability of 131mXe.

131mXe has been standardized by means of an internal gas proportional counting system, employing a length-compensated method. The activity concentration of 131mXe was measured with a relative standard uncertainty of 0.6%. The gamma-ray emission probability of 131mXe was then determined as 0.0196(4) by measuring a standard sample of 131mXe using a high-purity germanium (HPGe) spectrometer.

Alogliptin prevents diastolic dysfunction and preserves left ventricular mitochondrial function in diabetic rabbits.

BACKGROUND: There are increasing evidence that left ventricle diastolic dysfunction is the initial functional alteration in the diabetic myocardium. In this study, we hypothesized that alogliptin prevents diastolic dysfunction and preserves left ventricular mitochondrial function and structure in diabetic rabbits. METHODS: A total of 30 rabbits were randomized into control group (CON, n = 10), alloxan-induced diabetic group (DM, n = 10) and alogliptin-treated (12.5 mg/kd/day for 12 weeks) diabetic group (DM-A, n = 10). Echocardiographic and hemodynamic studies were performed in vivo. Mitochondrial morphology, respiratory function, membrane potential and reactive oxygen species (ROS) generation rate of left ventricular tissue were assessed. The serum concentrations of glucagon-like peptide-1, insulin, inflammatory and oxidative stress markers were measured. Protein expression of TGF-ß1, NF-κB p65 and mitochondrial biogenesis related proteins were determined by Western blotting. RESULTS: DM rabbits exhibited left ventricular hypertrophy, left atrial dilation, increased E/e' ratio and normal left ventricular ejection fraction. Elevated left ventricular end diastolic pressure combined with decreased maximal decreasing rate of left intraventricular pressure (- dp/dtmax) were observed. Alogliptin alleviated ventricular hypertrophy, interstitial fibrosis and diastolic dysfunction in diabetic rabbits. These changes were associated with decreased mitochondrial ROS production rate, prevented mitochondrial membrane depolarization and improved mitochondrial swelling. It also improved mitochondrial biogenesis by PGC-1α/NRF1/Tfam signaling pathway. CONCLUSIONS: The DPP-4 inhibitor alogliptin prevents cardiac diastolic dysfunction by inhibiting ventricular remodeling, explicable by improved mitochondrial function and increased mitochondrial biogenesis.