Atorvastatin ameliorated myocardial fibrosis in db/db mice by inhibiting oxidative stress and modulating macrophage polarization.

BACKGROUND: People with diabetes mellitus (DM) suffer from multiple chronic complications due to sustained hyperglycemia, especially diabetic cardiomyopathy (DCM). Oxidative stress and inflammatory cells play crucial roles in the occurrence and progression of myocardial remodeling. Macrophages polarize to two distinct phenotypes: M1 and M2, and such plasticity in phenotypes provide macrophages various biological functions. AIM: To investigate the effect of atorvastatin on cardiac function of DCM in db/db mice and its underlying mechanisms. METHODS: DCM mouse models were established and randomly divided into DM, atorvastatin, and metformin groups. C57BL/6 mice were used as the control. Cardiac function was evaluated by echocardiography. Hematoxylin and eosin and Masson staining was used to examine the morphology and collagen fibers in myocardial tissues. The expression of transforming growth factor-ß1 (TGF-ß1), tumor necrosis factor-α (TNF-α), interleukin-1 ß (IL-1ß),M1 macrophages (iNOS+), and M2 macrophages (CD206+) were demonstrated by immunohistochemistry and immunofluorescence staining. The levels of TGF-ß1, IL-1ß, and TNF-α were detected by ELISA and real-time quantitative polymerase chain reaction. Malondialdehyde (MDA) concentrations and superoxide dismutase (SOD) ac-tivities were also measured. RESULTS: Treatment with atorvastatin alleviated cardiac dysfunction and decreased db/db mice. The broken myocardial fibers and deposition of collagen in the myocardial interstitium were relieved especially by atorvastatin treatment. Atorvastatin also reduced the levels of serum lactate dehydrogenase, creatine kinase isoenzyme, and troponin; lowered the levels of TGF-ß1, TNF-α and IL-1ß in serum and myocardium; decreased the concentration of MDA and increased SOD activity in myocardium of db/db mice; inhibited M1 macrophages; and promoted M2 macrophages. CONCLUSION: Administration of atorvastatin attenuates myocardial fibrosis in db/db mice, which may be associated with the antioxidative stress and anti-inflammatory effects of atorvastatin on diabetic myocardium through modulating macrophage polarization.

Empagliflozin ameliorates diabetic cardiomyopathy probably via activating AMPK/PGC-1α and inhibiting the RhoA/ROCK pathway.

BACKGROUND: Diabetic cardiomyopathy (DCM) increases the risk of hospitalization for heart failure (HF) and mortality in patients with diabetes mellitus. However, no specific therapy to delay the progression of DCM has been identified. Mitochondrial dysfunction, oxidative stress, inflammation, and calcium handling imbalance play a crucial role in the pathological processes of DCM, ultimately leading to cardiomyocyte apoptosis and cardiac dysfunctions. Empagliflozin, a novel glucose-lowering agent, has been confirmed to reduce the risk of hospitalization for HF in diabetic patients. Nevertheless, the molecular mechanisms by which this agent provides cardioprotection remain unclear. AIM: To investigate the effects of empagliflozin on high glucose (HG)-induced oxidative stress and cardiomyocyte apoptosis and the underlying molecular mechanism. METHODS: Twelve-week-old db/db mice and primary cardiomyocytes from neonatal rats stimulated with HG (30 mmol/L) were separately employed as in vivo and in vitro models. Echocardiography was used to evaluate cardiac function. Flow cytometry and TdT-mediated dUTP-biotin nick end labeling staining were used to assess apoptosis in myocardial cells. Mitochondrial function was assessed by cellular ATP levels and changes in mitochondrial membrane potential. Furthermore, intracellular reactive oxygen species production and superoxide dismutase activity were analyzed. Real-time quantitative PCR was used to analyze Bax and Bcl-2 mRNA expression. Western blot analysis was used to measure the phosphorylation of AMP-activated protein kinase (AMPK) and myosin phosphatase target subunit 1 (MYPT1), as well as the peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) and active caspase-3 protein levels. RESULTS: In the in vivo experiment, db/db mice developed DCM. However, the treatment of db/db mice with empagliflozin (10 mg/kg/d) for 8 wk substantially enhanced cardiac function and significantly reduced myocardial apoptosis, accompanied by an increase in the phosphorylation of AMPK and PGC-1α protein levels, as well as a decrease in the phosphorylation of MYPT1 in the heart. In the in vitro experiment, the findings indicate that treatment of cardiomyocytes with empagliflozin (10 µM) or fasudil (FA) (a ROCK inhibitor, 100 µM) or overexpression of PGC-1α significantly attenuated HG-induced mitochondrial injury, oxidative stress, and cardiomyocyte apoptosis. However, the above effects were partly reversed by the addition of compound C (CC). In cells exposed to HG, empagliflozin treatment increased the protein levels of p-AMPK and PGC-1α protein while decreasing phosphorylated MYPT1 levels, and these changes were mitigated by the addition of CC. Adding FA and overexpressing PGC-1α in cells exposed to HG substantially increased PGC-1α protein levels. In addition, no sodium-glucose cotransporter (SGLT)2 protein expression was detected in cardiomyocytes. CONCLUSION: Empagliflozin partially achieves anti-oxidative stress and anti-apoptotic effects on cardiomyocytes under HG conditions by activating AMPK/PGC-1α and suppressing of the RhoA/ROCK pathway independent of SGLT2.

Tf2O/DMSO-Promoted P-O and P-S Bond Formation: A Scalable Synthesis of Multifarious Organophosphinates and Thiophosphates.

A Tf2O/DMSO-based system for the dehydrogenative coupling of a wide range of alcohols, phenols, thiols, and thiophenols with diverse phosphorus reagents has been developed. This metal- and strong-oxidant-free strategy provides a facile approach to a great variety of organophosphinates and thiophosphates. The simple reaction system, good functional-group tolerance, and broad substrate scope enable the application of this method to the modification of natural products and the direct synthesis of bioactive molecules and flame retardants.

Morphometric Trajectory Analysis for Occipital Condyle Screws.

OBJECTIVES: Occipitocervical fusion (OCF) is an effective treatment for instability of occipitocervical junction (OCJ). The occipital condyle screw serves as a novel surgical technique for occipitocervical fixation. However, the intraoperative procedures for the occipital condyle screw technique have relied on surgeons' experience, so the pool of surgeons who are able to perform this surgery safely is limited. The present study aims to evaluate the feasibility and safety of the occipital condyle screw technique using human cadavers and to provide image anatomy for clinical application basis. METHODS: The scientific study comprised 10 fresh-frozen cadaveric specimens from the anatomy department of Qingdao University. Placement of the occipital condyle screws (3.5 mm diameter and 20.0 mm length) was performed in the 10 fresh-frozen cadaveric specimens with intact occipitocervical junctions, respectively. Occipitocervical CT was performed for all specimens and the DICOM data was obtained. Occipitocervical CT three-dimensional (3D) reconstruction was performed for the cadavers. Morphometric analysis was performed on the bilateral occipitocervical junction of 10 cadaveric specimens based on the 3D reconstruction CT images. Detailed morphometric measurements of the 20 occipital condyles screws were conducted including the average length of the screw trajectory, inside and upper tilting angles of screws, distance to the hypoglossal canal, and to the medial wall of occipital condyle. RESULTS: Placement of the occipital condyle screws into the 20 occipital condyles of the 10 cadaveric specimens was performed successfully and the trajectory of implantation was satisfactory according to 3D CT reconstruction images, respectively. There was no obvious injury to the spinal cord, nerve root, and vertebral artery. The length of the bilateral screw trajectory was, respectively, 20.96 ± 0.91 mm (left) and 20.59 ± 0.77 mm (right) (t = 1.306, P > 0.05). The upper tilting angle of bilateral screws was, respectively, 11.24° ± 0.74° (left) and 11.11° ± 0.64° (right) (t = 0.681, P > 0.05). The inside tilting angle of bilateral screws was, respectively, 31.00° ± 1.32° (left) and 30.85° ± 1.27° (right) (t = 0.307, P > 0.05). The screw's distance to the bilateral hypoglossal canal was, respectively, 4.84 ± 0.54 mm (left) and 4.70 ± 0.54 mm (right) (t = 0.685, P > 0.05). The screw's distance to the medial wall of the bilateral occipital condyle was, respectively, 5.13 ± 0.77 mm (left) and 5.04 ± 0.71 mm (right) (t = 0.384, P > 0.05). CONCLUSION: The occipital condyle screw technique can serve as a feasible and safe treatment for instability of the occipitocervical junction with meticulous preoperative planning of the screw entry point and direction based on individual differences. Morphometric trajectory analysis is also an effective way to evaluate the surgical procedure.

[Effect of protein on the detection of antipsychotic drug residues in human serum and its elimination].

Using pure human serum albumin (HSA) as the model protein, the effects of protein on the extraction of antipsychotic drugs (APDs: diazepam, chlorpromazine hydrochloride, and perphenazine) in human serum sample were studied. The present paper investigated the interaction between APDs and HSA by fluorescence spectrometry in detail The influences of different ethanol concentration solution on protein denaturation were studied by Rayleigh scattering. The results showed that APDs strongly bound with HSA. In the phi (ethanol) 80% extracting solution, a slow but full protein denaturation takes place, which causes the unfolding of protein and the dissociation of drugs. Then K2 HPO4 was added into the extracting solution to form aqueous two-phase system, and meanwhile the drug residues were extracted into upper phase with high extraction efficiencies. After filtration, the upper phase was ready for analysis of drug residues by HPLC system. The detection limits were in the range of 18.8-38.4 ng x mL(-1), and the spiked recovery was 94.2%-98.7% for determination of antipsychotic drugs in human serum. The method is efficient, solvent-saving, environment-friendly, and accurate.

A novel technique of semi-aerobic aged refuse biofilter for leachate treatment.

We developed a semi-aerobic aged refuse biofilter (SAARB) for leachate treatment and examined its advantages and disadvantages compared to previous aged refuse biofilters (ARBs). To assess its treatment capability, decontamination mechanisms and optimal performance parameters, a single-period experiment and L(9)(3(4)) orthogonal array design experiments were conducted on artificial leachate. The SAARB markedly enhanced the treatment capability and removal efficiency of organic matter and nitrogen pollutants due to the alternating aerobic-anoxic-anaerobic zones in situ. The reduction in chemical oxygen demand (COD), ammonia nitrogen (NH(4)(+)-N) and total nitrogen (TN) exceeded 98%, 94%, and 80%, respectively. After the leachate was distributed onto the SAARB surface, the effluent velocity decreased as a logarithmic function, and there was a concomitant reduction in leachate effluent volume. Based on the capacity for removal of COD, NH(4)(+)-N, and TN, the effective height of aged refuse in a SAARB was enough to be 900mm. An excellent treatment efficiency could be achieved at 20-35°C, with a leachate distribution time of 1h once every period of 2-3 days, hydraulic loading of 11-30L/(m(3)day), and COD loading of 550-1200g/(m(3)day). This new SAARB system demonstrates superior efficacy for biofilter compared to other ARB systems, especially for nitrogen removal from leachate.

[Study on the interaction between alginic sodium diester and azur A and the application].

The interaction of alginic sodium diester (ASD) and azur A (AA) was studied by absorption spectra. The influence of pH and the molar ratio of AA/ASD on the spectra was investigated. The maximum binding number (N = 168) and the binding equilibrium constant (K = 3.25 x 10(6)) of the alginic sodium diester and azur A were obtained by the theoretical model. The new method for the determination of ASD was developed by the formation of ASD-AA ion-association complex that caused the fading of the AA. The detection limit is 0.009 microg x mL(-1). The method has the advantages of simplicity, stable system, good accuracy and selectivity, and was applied to the determination of alginic sodium diester in tablets with satisfactory results.

[Study on the adsorption behaviors of cadmium and lead ions on green tea and black tea by ICP-AES].

The adsorption behaviors of Cd(II) and Pb(II) on green tea and black tea in aqueous solution as well as the influences of time, acidity and temperature on the adsorption have been studied. It was found that Cd(II) and Pb(II) can been adsorbed strongly by green tea and black tea samples. The adsorption effects depend on the pH strongly when pH<4. The recovery of Pb(II) on tea samples is more than that of Cd(II) when pH<6 and it is opposite when pH>6. It is difficult to elute Cd(II) and Pb(II) from tea samples by water at 25 degrees C.

[Study on fluorescence characteristics of pefloxacin-La(III) complex and its application].

The complex of pefloxacin-La3+ was formed in the pH 5.6 HAc-NaAc buffer. Its fluorimetric intensity was 1.5 times that of the pefloxacin, and the excitation and emission peaks of the complex were at 276 and 440 nm, respectively. The new fluorescence method was developed for determining pefloxacin in serum based on the characteristics. The content of pefloxacin in serum was 4.79 mg x L(-1), the RSD and recovery were 6.3% and 95% respectively. The determination range was 0.04-2.0 mg x L(-1) with the detection limit of 2.8 microg x L(-1). The proposed method and UV-Vis photometric method were both applied to determining the pefloxacin in the same capsules with satisfactory results.

[Spectrophotometric method for the determination of water in organic solvents].

In the presence of a small amount of water, the chloranilic acid was disassociated. The absorption peak was bathochromic-shifted and the absorption intensity dramatically enhanced. Based on this fact, a spectrophotometric method was developed for determining water in many kinds of organic solvents. The mechanism and conditions for the determination were studied thoroughly. The water in alcohol samples (white wine, food alcohol and reagent alcohol) was detected with satisfactory results. The method was simple, sensitive and of good reproducibility. The linear range was phi(H2O) 0.02%-10% in alcohol. The method was also used for the determination of water in other organic solvents such as methanol, 2-propanol, acetone, butanone, acetonitrile and tetrahydrofuran, and the calibration curves were obtained, respectively.

[Study on fluorescence characteristics of pefloxacin based on charge transfer reaction].

The charge transfer complex formed between pefloxacin mesylate (PM) as the donor and tetrachlorobenzoquinone (TCQ) as the acceptor has been studied by fluorimetry. Experiment shows that PM reacted with TCQ in methanol with light and the complex was formed. Its fluorimetric intensity was stronger than that of PM and the excitation and emission peaks of the complex were red shifted to 80 nm and 60 nm, respectively. A linear calibration graph was obtained over the PM concentration from 0.05 micromol x L(-1) to 10 micromol x L(-1) with the detection limit of 0.004 micromol x L(-1) of PM. The proposed method and UV-Vis photometric method were both applied to determining the pefloxacin in the same capsules with satisfactory results.

[The progress of research on ginlcgobiobal flavone].

OBJECTIVE: The research on flavonoid in the recent years is extensive, such as Soybeans flavone, Baicalensis flavone, Epimedium flavone. Experiments show the effects of flavonoid is closely related to human health. There are a lot of reports about Ginkcobiobal flavone. In order to make further progress research on ginlcgobiobal flavone, we sum up the articles and reports on ginlcgobiobal flavone in the recent years. METHOD: To searche the articles about ginlcgobiobal flavone studies in the past five years. RESULT: Ginlcgobiobal flavone is not only a vasodilator, but also has the effects of anti-inflammation, analgesia, lowering blood lipids, preventing senile and inhibiting tumor, treating leukaemia, regulating gene and biotransformation. CONCLUSION: Ginlcgobiobal flavone has the potential value for drug research and development.