A study of the effects of SGLT-2 inhibitors on diabetic cardiomyopathy through miR-30d/KLF9/VEGFA pathway.

OBJECTIVE: The aim of this study was to observe the protective effects of SGLT-2 inhibitors on diabetic cardiomyopathy. MATERIALS AND METHODS: After constructing a diabetic rat model, the effects of SGLT-2 (Sodium-Glucose Cotransporter-2) inhibitors and miR-30d on cardiac function in rats were investigated by cardiac echocardiography, hematoxylin-eosin (HE) staining, and immunohistochemical methods. At the same time, changes in autophagy levels in rats were detected by Western blot (WB) experiments. RESULTS: SGLT-2 inhibitors improved the cardiac function of diabetic rats, and alleviated the pathological damage of myocardial tissue. Besides, knocking down miR-30d prevented the decrease of cardiac function in diabetic rats. Moreover, miR-30d could regulate the expression of the KLF9/VEGFA pathway and inhibit autophagy in rats. CONCLUSIONS: SGLT-2 inhibitors can regulate the autophagy level in diabetic rats through the miR-30d/KLF9/VEGFA pathway, thereby improving cardiac function.

The protective effect of lidocaine on lipopolysaccharide-induced acute lung injury in rats through NF-κB and p38 MAPK signaling pathway and excessive inflammatory responses.

OBJECTIVE: Acute lung injury is a severe disease with a high rate of mortality, leading to more important illness. We aimed at exploring the protective role and potential mechanisms of lidocaine on lipopolysaccharide (LPS)-induced acute lung injury (ALI). MATERIALS AND METHODS: Sprague Dawley (SD) rats were randomly assigned to control group receiving 0.9% saline solution, LPS group treated with 4 mg/kg LPS i.p., LPS + lidocaine(treated with 4 mg/kg LPS i.p. followed by giving 1 mg/kg, 3 mg/kg, 5 mg/kg of lidocaine i.v.). Lung specimens and the bronchoalveolar lavage fluid (BALF) were collected for histopathological examination and biochemical analyze 12 h after LPS induction. The cytokines expression of TNF-α, IL-6 and MCP-1 was measured by ELISA. In addition, the malondialdehyde (MDA) content, the activities of total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) in lung tissues were also detected using ELISA. The protein expressions of p38, p-p38, p65, p-p65 and IκB were analyzed by Western blot. RESULTS: The results indicated that after lidocaine treatment was able to decrease significantly wet-to-dry (W/D) ratio and ameliorate the histopathologic damage. Additionally, total protein content and the number of leukocytes in BALF significantly decreased. ELISA result indicated that the levels of TNF-α, IL-6 and MCP-1 in BALF were markedly suppressed. Meanwhile, the activities of T-AOC and SOD in lung tissues significantly increased, while the content of MDA significantly decreased after treatment with lidocaine. Moreover, Western blot suggested that lidocaine inhibited phosphorylation of NF-κB p65 and p38 MAPK. CONCLUSIONS: Therefore, lidocaine could ameliorate the LPS-induced lung injury via NF-κB/p38 MAPK signaling and excessive inflammatory responses, providing a potential for becoming the anti-inflammatory agent against lung injury.

A Randomised Controlled Trial to Evaluate the Effectiveness of Intrathecal Bupivacaine Combined with Different Adjuvants (Fentanyl, Clonidine and Dexmedetomidine) in Caesarean Section.

PURPOSE: The purpose of this study was to evaluate comparatively, in women undergoing caesarean section under spinal anesthesia, the effectiveness of hyperbaric bupivacaine combined with 3 different adjuvants (fentanyl, clonidine, and dexmedtomidine) on quality of blockade and maternal and neonatal repercussions. METHOD: 84 patients undergoing elective surgeries under spinal anesthesia were randomized into 4 groups of 21 each, gB, gBF, gBC and gBD. Patients in groups gb, gBF, gBC and gBD were given bupivacaine alone, bupivacaine plus fentanyl (15.0 µg), bupivacaine plus fentanyl plus clonidine (75 µg), and bupivacaine plus dexmedetomidine (10 µg), respectively. Hemodynamic parameters evaluated were the onset and level of sensory block, perioperative analgesia, degree and recovery time of motor block, duration of analgesia, sedation, and maternal-foetal repercussions. RESULTS: The onset of blockade was significantly faster in groups with adjuvants clonidine and dexmedetomidine compared with gB and gBF. Patients in Groups gB and gBF reported pain during the perioperative period. Duration of analgesia was significantly higher in Group gBD and was comparable to gBC and time to motor block recovery was significantly higher in Group gBD. Sedation was significant in Group gBD and gBC. CONCLUSION: Addition of dexmedetomidine and clonidine as adjuvants to hyperbaric bupivacaine provided adequate anesthesia and postoperative analgesia compared to fentanyl adjuvant without causing any significant side effects.

Fourier transform infrared spectroscopy approach for measurements of photoluminescence and electroluminescence in mid-infrared.

An improved Fourier transform infrared spectroscopy approach adapting to photoluminescence and electroluminescence measurements in mid-infrared has been developed, in which diode-pumped solid-state excitation lasers were adopted for photoluminescence excitation. In this approach, three different Fourier transform infrared modes of rapid scan, double modulation, and step scan were software switchable without changing the hardware or connections. The advantages and limitations of each mode were analyzed in detail. Using this approach a group of III-V and II-VI samples from near-infrared extending to mid-infrared with photoluminescence intensities in a wider range have been characterized at room temperature to demonstrate the validity and overall performances of the system. The weaker electroluminescence of quantum cascade lasers in mid-infrared band was also surveyed at different resolutions. Results show that for samples with relatively strong photoluminescence or electroluminescence out off the background, rapid scan mode is the most preferable. For weaker photoluminescence or electroluminescence overlapped with background, double modulation is the most effective mode. To get a better signal noise ratio when weaker photoluminescence or electroluminescence signal has been observed in double modulation mode, switching to step scan mode should be an advisable option despite the long data acquiring time and limited resolution.

Characterization of InAlAs/InGaAs/InP mid-infrared quantum cascade lasers.

A mid-infrared laser characterization system, including a GPIB programmable I-P and I-V set-up based on direct waveform measurement with extraordinary wide pulse duration and duty cycle tuning range, in conjunction with a Fourier transform infrared spectroscopy system adapted with double modulation technique, has been developed. Based on this characterization system, the characteristics of gas source MBE grown InAlAs/InGaAs/InP quantum cascade lasers (QCL), especially their thermal property, have been evaluated. The results show that in the combination of I-P, I-V and spectral measurements at various driving pulse parameters, the thermal resistance, lasing conditions as well as spectral characteristics of the mid-infrared QCL could be deduced. This characterization system is also a useful tool for the evaluation of other types of diode lasers in the mid-infrared band.

The iso-competition point for counterion competition binding to DNA: calculated multivalent versus monovalent cation binding equivalence.

In this paper we introduce an important parameter called the iso-competition point (ICP), to characterize the competition binding to DNA in a two-cation-species system. By imposing the condition of charge neutralization fraction equivalence theta1 = ZthetaZ upon the two simultaneous equations in Manning's counterion condensation theory, the ICPs can be calculated. Each ICP, which refers to a particular multivalent concentration where the charge fraction on DNA neutralized from monovalent cations equals that from the multivalent cations, corresponds to a specific ionic strength condition. At fixed ionic strength, the total DNA charge neutralization fractions thetaICP are equal, no matter whether the higher valence cation is divalent, trivalent, or tetravalent. The ionic strength effect on ICP can be expressed by a semiquantitative equation as ICPZa/ICPZb = (Ia/Ib)Z, where Ia, Ib refers to the instance of ionic strengths and Z indicates the valence. The ICP can be used to interpret and characterize the ionic strength, valence, and DNA length effects on the counterion competition binding in a two-species system. Data from our previous investigations involving binding of Mg2+, Ca2+, and Co(NH3)63+ to lambda-DNA-HindIII fragments ranging from 2.0 to 23.1 kbp was used to investigate the applicability of ICP to describe counterion binding. It will be shown that the ICP parameter presents a prospective picture of the counterion competition binding to polyelectrolyte DNA under a specific ion environment condition.

A gel electrophoresis study of the competitive effects of monovalent counterion on the extent of divalent counterions binding to DNA.

The behavior of alkaline earth metal cations (Mg2+ and Ca2+) and transition metal cations (Zn2+ and Cu2+) interacting with lambda-DNA-HindIII fragments ranging from 2,027 to 23,130 bp in Tris-borate-EDTA buffer solutions was investigated. The divalent counterions competed with Tris+ and Na+ for binding to polyion DNA, and the competition binding situations were investigated by measuring the reduction of the DNA mobility, by pulsed- or constant-field gel electrophoresis. The interaction of Mg2+ with DNA was intensively studied over a wide range of Mg2+ concentrations. In addition, we examined the competition binding as a function of ionic strength and DNA size. To compare valence effects, we studied Co(NH3)6(3+) interaction with DNA fragments under conditions similar to that of Mg2+. At relatively low Mg2+ concentration, the normalized titration curves of DNA mobility were well fit by Manning's two-variable counterion condensation (CC) theory. The agreement between the predicted value (total charge neutralization fraction theta) from Manning's CC theory and the data based on our measured DNA electrophoretic mobility reduction was consistent under our experimental conditions. In contrast to alkaline earth metal cations (Mg2+ and Ca2+), different binding behaviors were observed for the transition metal cations (Zn2+ and Cu2+). These differences highlight the usefulness of our reduced DNA electrophoretic mobility measurement approach to describing cation interactions with polyelectrolyte DNA.

Trivalent counterion condensation on DNA measured by pulse gel electrophoresis.

Pulse gel electrophoresis was used to measure the reduction of mobilities of lambda-DNA-Hind III fragments ranging from 23.130 to 2.027 kilobase pairs in Tris borate buffer solutions mixed with either hexammine cobalt(III), or spermidine3+ trivalent counterions that competed with Tris+ and Na+ for binding onto polyion DNA. The normalized titration curves of mobility were well fit by the two-variable counterion condensation theory. The agreement between measured charge fraction neutralized and counterion condensation prediction was good over a relatively wide range of trivalent cation concentrations at several solution conditions (pH, ionic strength). The effect of ionic strength, trivalent cation concentration, counterion structure, and DNA length on the binding were discussed based on the experimental measurements and the counterion condensation theory.

Formation study of toroidal condensation of DNA.

A detailed study of the formation of toroidal condensation produced from the 2700 base pair fragments of plasmid PUC13 DNA, induced by metal ions, is introduced. We have extracted several typical intermediate structures based on investigation by electron microscopy, and compared their size distributions. The observations suggest that the formation process of DNA condensation is the process of folding and arranging DNA chains and that of disorder-order transition. The result also indicates that the condensed particles are polymeric, but not randomly aggregative, further proving the toroidal structures are formed in certain regularities.

Condensation of DNA by trivalent cations. 1. Effects of DNA length and topology on the size and shape of condensed particles.

In vitro condensation of DNA by multivalent cations can provide useful insights into the physical factors governing folding and packaging of DNA in vivo. We have made a detailed study of hexammine cobalt (III) induced condensation of 2700 and 1350 base pair (bp) fragments of plasmid pUC12 DNA by electron microscopy and laser light scattering. The condensed DNA takes the form of toroids and rods. Both are present in all condensates, but the proportion of toroids is higher with the larger fragments. The intact, closed circular plasmid produces smaller particles than the linear fragments. The size of a particle is independent of DNA fragment length. Two hours after adding the condensing agent, a typical toroid is about 800 A in diameter; the outer radius (R1) is approximately 400 A, and the inner radius (R2) is approximately 140 A for both sets of fragments. These dimensions are relatively stable, but there is sufficient change in both R1 and R2 to produce approximately 50% increase in volume from 2 to 24 h. A typical rod at 2 h is about 1800 A long and 300 A wide. The distribution of rod lengths is similar to that of mean toroid circumferences pi (R1 + R2), and the distribution of rod widths is similar to that of toroidal widths (R1-R2). The 2700-bp fragments show a significantly higher ratio of toroids to rods than the 1350-bp fragments. Both types of particle are multimolecular. The average number of molecules/particle, calculated from the above dimensions, assuming hexagonally packed B-form DNA with a center-to-center spacing of 27 A, is 13 +/- 4 for condensates of 2700-bp fragments and 26 +/- 11 for those of 1350-bp fragments. Monomolecular condensates of much larger DNAs have similar dimensions, suggesting that size is governed primarily by the balance of attractive and repulsive intermolecular forces rather than by the entropic factors associated with incorporation of a number of small particles into a larger one. The similar dimensions and volumes of toroids and rods indicate that the free energy cost of continual bending in toroids, minus that gained by extra net attraction in a cyclic particle, is comparable to that of abrupt bending or kinking in rods. Although the condensed particles are multimeric, their distinct toroidal or rodlike shapes distinguish them from the random aggregates that would be generally expected from the multimolecular association of large, flexible polymers.