Production of St. John's wort plants under controlled environment for maximizing biomass and secondary metabolites

Summary St. John's wort (Hypericum perforatum L.) is a medicinal plant used in the treatment of neurological disorders and has been recently shown to have anticancer potential. The principle medicinal components of St. John's wort are hypericin. pseudohypericin, and hyperforin. One of the problems associated with medicinal plant preparations including St. John's wort is the extreme variability in the phytochemical content, mostly due to environmental variability, and biotic and abiotic contamination during cropping. The current study was undertaken to transplant St. John's wort plants from in vitro bioreactors in a closed controlled environment system (CCES) with CO₂ enrichment for the optimized production of biomas and phytochemicals. The growth and levels of hypericin, pseudohypericin, and hyperforin in plants grown in CCES were compared with those of the greenhouse and in vitro-grown plants. The environmental parameters in the greenhouse were found to be variable whereas in the CCES these parameters were controlled. Generally, all the growth parameters and hypericin and psendohypericin levels were significantly higher in the plants grown in the CCES. These results provide the first indication that growing St. John's wort plants, under CO₂ enrichment in a closed environment system can enhance the biomass and medicinal contents. The adaptation of this growing system may be useful for the production of optimized products of St. John's wort and other medicinal species.     

Molecular identification, immunolocalization, and functional activity of a vacuolar-type H+-ATPase in bovine rumen epithelium

In this study, we have studied the expression, localization, and functionality of vacuolar-type H⁺-ATPase (vH⁺-ATPase) and Na⁺/K⁺-ATPase in the bovine rumen epithelium. Compared with the intracellular pH (pH_i) of control rumen epithelial cells (REC; 7.06 ± 0.07), application of inhibitors selective for vH⁺-ATPase (foliomycin) and Na⁺/K⁺-ATPase (ouabain) reduced pH_i by 0.10 ± 0.03 and 0.18 ± 0.03 pH-units, respectively, thereby verifying the existence of both functional proteins. Results from qRT-PCR and immunoblotting clearly confirm the expression of vH⁺-ATPase B subunit in REC. However, the amount of Na⁺/K⁺-ATPase mRNA and protein is tenfold and 11-fold of those of vH⁺-ATPase subunit B, respectively, reflecting a lower overall abundance of the latter in REC. Na⁺/K⁺-ATPase immunostaining has revealed the protein in the plasma membrane of all REC from the stratum basale to stratum granulosum, with the highest abundance in basal cells. In contrast, the vH⁺-ATPase B subunit has been detected in groups of cells only, mainly localized in the stratum spinosum and stratum granulosum of the epithelium. Furthermore, vH⁺-ATPase has been detected in the cell membrane and in intracellular pools. Thus, functional vacuolar-type H⁺ pumps are expressed in REC and probably play a role in the adaptation of epithelial transport processes.     

100Hz电针刺受时大鼠脑和脊髓k受体结构特性的改变

西方采用放射配体结合实验研究了１００ＨＺ电针耐受发生发展过程中大鼠脑和脊髓Ｋ受体结构特性的变化。大鼠每天给予１００ＨＺ电针１次,连续７ｄ。分别在电针的第１、３、５、７天取不同脑区进行观察。     

Effects of sodium glucose cotransporter-2 inhibitors on serum uric acid in type 2 diabetes mellitus: A systematic review with an indirect comparison meta-analysis

To describe the effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors on serum uric acid (SUA) in patients with type 2 diabetes mellitus (T2DM). PubMed, EMBASE, and CENTRAL were searched for randomized controlled trials of SGLT2 inhibitors in patients with T2DM up to Aug 10, 2017, without language or date restrictions. Thirty-one studies totaling 13,650 patients were included. SGLT2 inhibitors significantly decreased SUA levels compared with placebo, canagliflozin WMD –37.02?μmol/L, 95% CI [–38.41, –35.63], dapagliflozin WMD –38.05?μmol/L, 95% CI [–44.47, –31.62], empagliflozin WMD –42.07?μmol/L, 95% CI [–46.27, –37.86]. The drug class effect of SUA reduction suggesting SGLT2 inhibitors might be beneficial for diabetic patients with hyperuricemia.     

Opioidergic effects of nonopioid analgesics on the central nervous system

1. The analgesic effect of nonsteroidal anti-inflammatory drugs (NSAIDs) is partly due to the fact that they act upon the periaqueductal gray matter (PAG) and the rostral ventromedial medulla of the brain stem and thus activate the descending pain-control system, which inhibits nociceptive transmission at the spinal dorsal horn.2. The analgesic action of dipyrone (metamizol) and of lysine-acetylsalicylate (LASA), two well-known NSAIDs, whether microinjected into the PAG or given systemically, can be reverted by naloxone. Repeated administration of dipyrone or LASA induces tolerance to their antinociceptive effect, with cross-tolerance to morphine, and a withdrawal syndrome upon naloxone administration. Dipyrone tolerance can be reverted by proglumide, a cholecystokinin antagonist.3. These findings reveal a close association between the central action of NSAIDs and endogenous opioids.     

Development and validation of a weight-bearing finite element model for total knee replacement

Total knee arthroplasty (TKA) is a successful procedure for osteoarthritis. However, some patients (19%) do have pain after surgery. A finite element model was developed based on boundary conditions of a knee rig. A 3D-model of an anatomical full leg was generated from magnetic resonance image data and a total knee prosthesis was implanted without patella resurfacing. In the finite element model, a restarting procedure was programmed in order to hold the ground reaction force constant with an adapted quadriceps muscle force during a squat from 20° to 105° of flexion. Knee rig experimental data were used to validate the numerical model in the patellofemoral and femorotibial joint. Furthermore, sensitivity analyses of Young’s modulus of the patella cartilage, posterior cruciate ligament (PCL) stiffness, and patella tendon origin were performed. Pearson’s correlations for retropatellar contact area, pressure, patella flexion, and femorotibial ap-movement were near to 1. Lowest root mean square error for retropatellar pressure, patella flexion, and femorotibial ap-movement were found for the baseline model setup with Young’s modulus of 5 MPa for patella cartilage, a downscaled PCL stiffness of 25% compared to the literature given value and an anatomical origin of the patella tendon. The results of the conducted finite element model are comparable with the experimental results. Therefore, the finite element model developed in this study can be used for further clinical investigations and will help to better understand the clinical aspects after TKA with an unresurfaced patella.     

Computer simulation of synchronization of Na/K pump molecules

The behavior of Na/K pump currents when exposed to an oscillating electric field is studied by computer simulation. The pump current from a single pump molecule was sketched based on previous experimental results. The oscillating electric field is designed as a symmetric, dichotomous waveform varying the membrane potential from −30 to −150 mV around the membrane resting potential of −90 mV. Based on experimental results from skeletal muscle fibers, the energy needed to overcome the electrochemical potentials for the Na and K-transports are calculated in response to the field’s two half-cycles. We found that a specially designed oscillating electric field can eventually synchronize the pump molecules so that all the individual pumps run at the same pumping rate and phase as the field oscillation. They extrude Na ions during the positive half-cycle and pump in K ions during the negative half-cycle. The field can force the two ion-transports into the corresponding half-cycles, respectively, but cannot determine their detailed positions. In other words, the oscillating electric field can synchronize pumps in terms of their pumping loops but not at a specific step in the loop. These results are consistent with our experimental results in measurement of the pump currents.     

Meta-analysis: Four-Drug, Three-Antibiotic, Non-bismuth-Containing "Concomitant Therapy" Versus Triple Therapy for Helicobacter pylori Eradication

Background: Low success rates with triple therapy for Helicobacter pylori infections have prompted search for alternatives. In one, a proton-pump inhibitor (PPI) and amoxicillin was followed by the PPI plus clarithromycin and a nitroimidazole (sequential therapy); in another, these four drugs were given concomitantly (concomitant therapy).
Aim: To compare concomitant therapy with standard triple therapy for H. pylori infection.
Methods: By searching PubMed, EMBASE, the Cochrane Central Register of Controlled Trials and abstracts of major gastrointestinal meeting, two independent reviewers systemically identified randomized controlled trials (RCT) comparing concomitant quadruple to standard triple therapies as well as studies reporting eradication rates of concomitant quadruple therapy in treatment of H. pylori . Pooled eradication rates and odds ratios (OR) with 95% confidence intervals (CI) were calculated, and univariable metaregression analysis for all extracted variables was conducted.
Results: We identified nine studies (10 treatment arms) including five qualifying RCTs (576 subjects) comparing concomitant (293 subjects, duration 3 to 5 days) and triple therapy (283 subjects, duration 5 to 10 days) and four other studies evaluating concomitant therapy (478 subjects, duration 3 to 7 days). Pooled estimates of the five RCTs showed superiority of concomitant therapy over triple therapy; with intention-to-treat) pooled OR of 2.86 (95% CI: 1.73–4.73) and per-protocol (PP) pooled OR of 3.52 (95% CI: 1.95–6.38). Considering all 10 treatment arms, the ITT eradication rate was 89.7% (95% CI: 86.8–92.1%) and PP was 92.9% (95% CI: 90.2–94.8%).
Conclusion: Concomitant therapy appears to be an effective alternative to triple therapy and is less complex than sequential therapy.     

Triggered release of ciprofloxacin from nanostructured agglomerated vesicles

Nanostructured agglomerated vesicles encapsulating ciprofloxacin were evaluated for modulated delivery from the lungs in a healthy rabbit model. An aliphatic disulfide crosslinker, cleavable by cysteine was used to form cross-links between nanosized liposomes to form the agglomerates. The blood levels of drug after pulmonary instillation of free ciprofloxacin, liposomal ciprofloxacin, and the agglomerated liposomes encapsulating ciprofloxacin were evaluated. The liposomes and agglomerated vesicles showed extended release of drug into the blood over 24 hours, while the free ciprofloxacin did not. The agglomerates also allowed modulation of the drug release rate upon the introduction of cysteine into the lungs post-drug instillation; the cysteine-cleavable agglomerates accelerated their drug release rate, indicated by an increased level of drug in the blood. This technology holds promise for the post-administration modulation of antibiotic release, for the prevention and treatment of pulmonary and systemic infections.