Improvement of high-glucose and insulin resistance of chromium malate in 3T3-L1 adipocytes by glucose uptake and insulin sensitivity signaling pathways and its mechanism

Previous study has revealed that chromium malate could improve insulin resistance and the regulation of fasting blood glucose in type 2 diabetic rats. This study was designed to investigate the effect of chromium malate on hypoglycemic and improve insulin resistance activities in 3T3-L1 adipocytes with insulin resistance and investigate the acting mechanism. The result indicated that chromium malate exhibited direct hypoglycemic activity in vitro. Compared with the model group, chromium malate could significantly promote the expression levels of GLUT-4, Akt, Irs-1, PPARγ, PI3K and p38-MAPK and their mRNA, increase p-AKT/AKT level, AKT and AMPKβ1 phosphorylation and reduce Irs-1 phosphorylation and p-Irs-1/Irs-1 level in 3T3-L1 adipocytes (p < 0.05). Chromium malate is more effective in regulating the proteins and mRNA expressions than those of chromium trichloride and chromium picolinate. Compared to the model group, pretreatment with the specific p38-MAPK inhibitor completely inhibited the GLUT-4 and Irs-1 proteins and mRNA expressions induced by the chromium malate. In conclusion, chromium malate had a beneficial influence on improvement of controlling glucose levels and insulin resistance in 3T3-L1 adipocytes with insulin resistance by regulating proteins productions and genes expressions in glucose uptake and insulin sensitivity signaling pathways.

Chromium malate could increase the related protein and mRNA levels in 3T3-L1 adipocytes with insulin resistant. Pretreatment with the inhibitor completely/partially inhibited the GLUT-4 and Irs-1 proteins and mRNA expression compared to model group.     

Toxic trace elements at gastrointestinal level

Many trace elements are considered essential [iron (Fe), zinc (Zn), copper (Cu)], whereas others may be harmful [lead (Pb), cadmium (Cd), mercury (Hg), arsenic (As)], depending on their concentration and chemical form. In most cases, the diet is the main pathway by which they enter our organism. The presence of toxic trace elements in food has been known for a long time, and many of the food matrices that carry them have been identified. This has led to the appearance of legislation and recommendations concerning consumption. Given that the main route of exposure is oral, passage through the gastrointestinal tract plays a fundamental role in their entry into the organism, where they exert their toxic effect. Although the digestive system can be considered to be of crucial importance in their toxicity, in most cases we do not know the events that occur during the passage of these elements through the gastrointestinal tract and of ascertaining whether they may have some kind of toxic effect on it. The aim of this review is to summarize available information on this subject, concentrating on the toxic trace elements that are of greatest interest for organizations concerned with food safety and health: Pb, Cd, Hg and As.     

Just an additional hydrogen bond can dramatically reduce the catalytic activity of Bacillus subtilis lipase A I12T mutant: An integration of computational modeling and experimental analysis

Understanding the structural basis and energetic property of hydrogen bonding and its effects on enzymatic activity is fundamentally important for the rational design of specific enzymes with desired biological functions. In the current study, site-directed mutagenesis analysis preliminarily revealed that the amino acid substitution of Ile12 with Thr12 (I12T) dramatically reduced the hydrolytic activity of Bacillus subtilis lipase A. A further computational investigation proposed that the I12T mutation would establish a geometrically perfect hydrogen bond between the mutated Thr12 and catalytic Ser77 of lipase A, which considerably impaired the catalytic capability of lipase A through two distinct but complementary approaches: rigidizing the enzyme active site and lowering the nucleophilic ability of the catalytic residue Ser77. To verify this hypothesis, a homogenous mutation I12S serving as the control to the I12T mutation was created to examine the hydrogen bonding effect on enzymatic activity. It was found that the I12S mutant only suffered from a slight damage in its hydrolytic ability due to absence of the hydrogen bond originally present at the Thr12–Ser77 interface in the I12T mutant, which was further characterized systematically by quantum mechanics/molecular mechanics (QM/MM) modeling, atom-in-molecules (AIM) analysis and molecular dynamics (MD) simulation. It is suggested that the hydrogen bond arising from the I12T mutation in lipase A can considerably reduce the flexibility and mobility of the enzyme active site, thus impairing the catalytic activity of the lipase A I12T mutant remarkably; the activity loss can be, however, largely recovered by replacing Thr residue at the 12th position of I12T mutant with its analog Ser, which is chemically similar to Thr but cannot form effective hydrogen bonding with Ser77.     

Study on stable equilibrium of levitated impeller in rotary pump with passive magnetic bearings

It is widely acknowledged that the permanent maglev cannot achieve stable equilibrium; the authors have developed, however, a stable permanent maglev centrifugal blood pump. Permanent maglev needs no position detection and feedback control of the rotor, nevertheless the eccentric distance (ED) and vibration amplitude (VA) of the levitator have been measured to demonstrate the levitation and to investigate the factors affecting levitation. Permanent maglev centrifugal impeller pump has a rotor and a stator. The rotor is driven by stator coil and levitated by two passive magnetic bearings. The rotor position is measured by four Hall sensors, which are distributed evenly and peripherally on the end of the stator against the magnetic ring of the bearing on the rotor. The voltage differences of the sensors due to different distances between the sensors and the magnetic ring are converted into ED. The results verify that the rotor can be disaffiliated from the stator if the rotating speed and the flow rate of the pump are large enough, that is, the maximal ED will reduce to about half of the gap between the rotor and the stator. In addition, the gap between rotor and stator and the viscosity of the fluid to be pumped also affect levitation. The former has an optimal value of ≈ 2% of the radius of the rotor. For the latter, levitation stability is better with higher viscosity, meaning smaller ED and VA. The pressure to be pumped has no effect on levitation.     

Measurement of rotary pump flow and pressure by computation of driving motor power and speed

Measurement of pump flow and pressure by ventricular assist is an important process, but difficult to achieve. On one hand, the pump flow and pressure are indicators of pump performance and the physiologic status of the receptor, meanwhile providing a control basis of the blood pump itself. On the other hand, the direct measurement forces the receptor to connect with a flow meter and a manometer, and the sensors of these meters may cause haematological problems and increase the danger of infection. A novel method for measuring flow rate and pressure of rotary pump has been developed recently. First the pump performs at several rotating speeds, and at each speed the flow rate, pump head and the motor power (voltage x current) are recorded and shown in diagrams, thus obtaining P (motor power) - Q (pump volume) curves as well as P - H (pump head) curves. Secondly, the P, n (rotating speed) values are loaded into the input layer of a 3-layer BP (back propagation) neural network and the Q and H values into the output layer, to convert P-Q and P-H relations into Q=f (P,n) and H=g (P, n) functions. Thirdly, these functions are stored by computer to establish a database as an archive of this pump. Finally, the pump flow and pressure can be computed from motor power and speed during animal experiments or clinical trials. This new method was used in the authors' impeller pump. The results demonstrated that the error for pump head was less than 2% and that for pump flow was under 5%, so its accuracy is better than that of non-invasive measuring methods.     

Axial reciprocation of rotating impeller: a new concept of antithrombogenecity in centrifugal pump

For long-term application, rotary pumps have to solve the problems of bearing wear and thrombosis along the bearing. Most investigators choose the magnetic bearing to realize zerofriction and no contact between the rotor and stator; the former avoids the mechanical wear and the latter eliminates the possibility of thrombus formation. The authors have tried and found, however, that it is difficult to apply a magnetic bearing to the rotary pump without disturbing its simplicity, reliability and implantability, and have therefore developed a much simpler and much more creative approach to achieve the same results. Instead of using a sliding bearing, a rolling bearing has been devised for the pump, and its friction is about 1/15 of the sliding bearing. Furthermore, a wear-proof material of ultra-high-molecular weight polythene has been adopted to make the rollers, and its anti-wear property is 8 times better than metal. Thereby, the service life of the bearing has been prolonged to ten years according to the documents provided by the producer. In order to prevent the thrombus formation along the bearing, the impeller reciprocates axially as the impeller changes its rotating speed periodically to produce a pulsatile flow. The reciprocation is the result of the effects of a magnetic force between the motor rotor and stator, and a hydraulic force between the blood flow and the impeller. Similar to a piston pump, the oscillating impeller can make the blood flow in and out of the bearing, resulting in wash-out once a circle. This obviously helps to prevent thrombosis along the bearing and in the pump. The endurance tests with saline of this novel pump demonstrated the durability of the device. It promises to be able to assist the circulation of patients permanently, and to be able to replace heart transplantation in the future.     

Technical note: A novel impeller TAH using magnetic bearings for load reduction

A novel impeller TAH (total artificial heart), i.e. bi-ventricular assist impeller pumps, has been developed. The device consists of a rotor with motor magnets and two impellers, a stator with motor coil and iron core, and two pump housings. In both sides of the rotor magnets, as well as the stator coil core, a pair of magnetic bearings was devised to partly counteract the attractive forces between the rotor magnets and the stator coil core. This means the magnetic bearings are used for load reduction. On hydrodynamic testing, the two pumps both produced a flow rate as high as 6 l min -1 and the left pump had a pressure head of 150 mm Hg, and that of the right pump was 50 mm Hg. The highest efficiency of the device, including the motor, the two pumps and the controller, reached 14.7%. The device, weighing 250 g, had a length of 80 mm and a diameter of 40 mm at its largest point. Currently in the world, this is a unique TAH, which is electrically powered and driven by a single motor and has only one moving part, can produce either pulsatile or non-pulsatile flow, both pumps eject flow synchronistically by pulsatile mode, and the volume equilibrium of the two pumps can be achieved automatically without the need for control.     

Comparative proteomics reveals essential mechanisms for osmotolerance in Gluconacetobacter diazotrophicus

Plant growth-promoting bacteria are a promising alternative to improve agricultural sustainability. Gluconacetobacter diazotrophicus is an osmotolerant bacterium able to colonize several plant species, including sugarcane, coffee, and rice. Despite its biotechnological potential, the mechanisms controlling such osmotolerance remain unclear. The present study investigated the key mechanisms of resistance to osmotic stress in G. diazotrophicus. The molecular pathways regulated by the stress were investigated by comparative proteomics, and proteins essential for resistance were identified by knock-out mutagenesis. Proteomics analysis led to identify regulatory pathways for osmotic adjustment, de novo saturated fatty acids biosynthesis, and uptake of nutrients. The mutagenesis analysis showed that the lack of AccC protein, an essential component of de novo fatty acid biosynthesis, severely affected G. diazotrophicus resistance to osmotic stress. Additionally, knock-out mutants for nutrients uptake (Δtbdr and ΔoprB) and compatible solutes synthesis (ΔmtlK and ΔotsA) became more sensitive to osmotic stress. Together, our results identified specific genes and mechanisms regulated by osmotic stress in an osmotolerant bacterium, shedding light on the essential role of cell envelope and extracytoplasmic proteins for osmotolerance.     

左心室辅助装置控制模式影响双心室搏动同步性的数值研究

右心室(RV)衰竭已成为左心室辅助装置(LVAD)治疗的一种致命并发症。由LVAD引起的双心室搏动的不同步是引发RV功能障碍的重要因素。本文采用数值方法研究LVAD的控制模式对左、右心室搏动同步性的影响。数值结果表明:左心室(LV)与RV的收缩持续时间在无泵模式下没有显著差异(分别为48.52%和51.77%)。连续模式下,LV收缩期明显短于RV收缩期(LV vs.RV:24.38%vs.49.16%)和无泵模式的LV收缩期。搏动模式下,LV收缩期明显短于RV收缩期(LV vs.RV:28.38%vs.50.41%)但长于连续模式的LV收缩期。反搏动模式中的LV、RV收缩期差异较小(LV vs.RV:43.13%vs.49.23%),而LV收缩期短于无泵模式,并且长于连续模式。与连续和搏动模式相比,由反搏动模式提供的收缩期转速(RS)降低显著地校正了LV收缩持续时间,连续模式下缩短的收缩持续时间在反搏动模式下被校正为LV和RV之间的重新同步。因此,本文认为LV和RV收缩的再同步有助于预防RV功能障碍。总之,使用在收缩期间降低RS的反搏动模式有望用于由LVAD引起的双心室搏动不同步的临床校正。