Effects of Lifestyle Modification Programs on Cardiac Risk Factors

Medicare conducted a payment demonstration to evaluate the effectiveness of two intensive lifestyle modification programs in patients with symptomatic coronary artery disease: the Dr. Dean Ornish Program for Reversing Heart Disease (Ornish) and Cardiac Wellness Program of the Benson-Henry Mind Body Institute. This report describes the changes in cardiac risk factors achieved by each program during the active intervention year and subsequent year of follow-up. The demonstration enrolled 580 participants who had had an acute myocardial infarction, had undergone coronary artery bypass graft surgery or percutaneous coronary intervention within 12 months, or had documented stable angina pectoris. Of these, 98% completed the intense 3-month intervention, 71% the 12-month intervention, and 56% an additional follow-up year. Most cardiac risk factors improved significantly during the intense intervention period in both programs. Favorable changes in cardiac risk factors and functional cardiac capacity were maintained or improved further at 12 and 24 months in participants with active follow-up. Multivariable regressions found that risk-factor improvements were positively associated with abnormal baseline values, Ornish program participation for body mass index and systolic blood pressure, and with coronary artery bypass graft surgery. Expressed levels of motivation to lose weight and maintain weight loss were significant independent predictors of sustained weight loss (p = 0.006). Both lifestyle modification programs achieved well-sustained reductions in cardiac risk factors.     

Quantitative characterization of postnatal growth trends in proximal pulmonary arteries in rats by phase-contrast magnetic resonance imaging

Malformations of the pulmonary arteries can increase right heart workload and result in morbidity, heart failure, and death. With the increased use of murine models to study these malformations, there is a pressing need for an accurate and noninvasive experimental technique that is capable of characterizing pulmonary arterial hemodynamics in these animals. We describe the growth trends of pulmonary arteries in 13 male Sprague-Dawley rats at 20, 36, 52, 100, and 160 days of age with the introduction of phase-contrast MRI as such a technique. PCMRI results correlated closely with cardiac output measurements by ultrasound echocardiography and with fluorescent microspheres in right-left lung flow split (flow partition). Mean flow, average cross-sectional area, distensibility, and shear rates for the right and left pulmonary arteries (RPA and LPA) were calculated. The RPA was larger and received more flow at all times than the LPA (P < 0.0001). Right-left flow split did not change significantly with age, and arterial distensibility was not significantly different between RPA and LPA, except at 160 days (P < 0.01). Shear rates were much higher for the LPA than the RPA (P < 0.0001) throughout development. The RPA and LPA showed different structure-function relationships but obeyed similar allometric scaling laws, with scaling exponents comparable to those of the main pulmonary artery. This study is the first to quantitatively describe changes in RPA and LPA flows and sizes with development and to apply phase-contrast MRI techniques to pulmonary arteries in rats.     

Biocontrol Agent Talaromyces flavus Stimulates the Growth of Cotton and Potato

Beneficial plant-microbe interactions in the rhizosphere are primary determinants of plant health and soil fertility. Some antagonistic fungi have shown great effects toward the growth of plant crops. In this study, two major crops, cotton and potato, were selected to evaluate their growth promotion by the antagonistic fungus Talaromyces flavus. For each plant, five T. flavus isolates were selected from our fungal collection which had shown the highest antagonistic activities against the causal agent of wilt diseases on these plants. In the next step, for every crop, five isolates were used under greenhouse conditions. For evaluation of the plant growth promotion ability of T. flavus isolates, a split-plot trial was arranged in a randomized complete block design with four replications. The main factor was the method of application of T. flavus as a soil treatment, a seed treatment, and a combination of both methods. The subfactor was the use of different fungal isolates. Measured parameters were root length, crown length, plant height, plant fresh weight, and plant dry weight. Results showed that the maximum increase in the above parameters was mediated by the seed treatment method. The most effective isolate for cotton plants was TF-Co-M-23, which increased root length, plant height, plant fresh weight, and plant dry weight by 1.80-, 2.26-, 1.23-, and 1.19-fold, respectively. There were no significant differences among the various treatments affected by T. flavus in terms of crown length. The most effective isolate for potato plants was TF-Po-V-50, which increased root length, crown length, plant height, and plant dry weight by 1.71-, 1.09-, 1.45-, and 3.75-fold, respectively. The overall results of this study suggest that it may be possible to promote cotton and potato growth characteristics by using the antagonistic fungus T. flavus.     

Effect of chronic L-Arginine supplementation on aortic fatty streak formation and serum nitric oxide concentration in normal and high-cholesterol fed rabbits

Several reports indicated the beneficial effects of short-term L-Arginine (L-Arg) administration on atherosclerosis processes. The aim of this study was to evaluate the effect of chronic L-Arg supplementation on serum lipid profile, aortic Fatty Streak (FS) formation, and serum Nitric oxide (NO) concentration in Normal Diet (ND) and High-Cholesterol Diet (HCD) fed rabbits. 24 male rabbits were randomly divided into four groups (n=6 in each group) (i): ND for seven months; (ii): ND for 1 month plus ND + L-Arg for six months; (iii): HCD (1%) for 1 month plus HCD (0.5%) for six months; (iv): HCD (1%) for 1 month plus HCD (0.5%) + L-Arg for six months. At the end of the study, histological evaluation of aortic FS formation was performed. Blood samples were taken for serum lipid profile and NO concentrations. L-Arg did not change serum total cholesterol, triglyceride, LDL and LDL/HDL ratio in normal and hypercholesterolemic rabbits (p>0.05). Histological examination of thoracic aortae revealed that the HCD group had higher FS formation compared to the ND group (2.1 ± 0.16 vs. 0 ± 0; respectively; p<0.05) and L-Arg supplementation did not attenuate FS formation in the HCD group (1.93 ± 0.17 compare to 2.1 ± 0.16; p>0.05). Serum NO level in the HCD group was higher than ND groups (p<0.05). Chronic L-Arg supplementation did not alter serum NO concentration either in the hypercholesterolemic or in the ND group (p>0.05). It seems that chronic L-Arg supplementation does not have beneficial effects on aortic fatty streak formation, serum lipids and NO concentrations in this model of experimental hypercholesterolemia.     

Cytotoxic and apoptotic properties of a novel nano-toxin formulation based on biologically synthesized silver nanoparticle loaded with recombinant truncated pseudomonas exotoxin A

Bacterial toxins have received a great deal of attention in the development of antitumor agents. Currently, these protein toxins were used in the immunotoxins as a cancer therapy strategy. Despite the successful use of immunotoxins, immunotherapy strategies are still expensive and limited to hematologic malignancies. In the current study, for the first time, a nano-toxin comprised of truncated pseudomonas exotoxin (PE38) loaded silver nanoparticles (AgNPs) were prepared and their cytotoxicity effect was investigated on human breast cancer cells. The PE38 protein was cloned into pET28a and expressed in Escherichia coli, BL21 (DE3), and purified using metal affinity chromatography and was analyzed by 15% sodium dodecyl sulfate-polyacrylamide gel electrophoresis. AgNPs were biologically prepared using cell-free supernatant of E. Coli K12 strain. Nanoparticle formation was characterized by energy dispersive spectroscopy, transmission electron microscopy, and dynamic light scattering. The PE38 protein was loaded on AgNPs and prepared the PE38-AgNPs nano-toxin. Additionally, in vitro release indicated a partial slow release of toxin in about 100 hr. The nano-toxin exhibited dose-dependent cytotoxicity on MCF-7 cells. Also, real-time polymerase chain reaction results demonstrated the ability of nano-toxin to upregulate Bax/Bcl-2 ratio and caspase-3, -8, -9, and P53 apoptotic genes in the MCF-7 tumor cells. Apoptosis induction was determined by Annexin-V/propidium flow cytometry and caspases activity assay after treatment of cancer cells with the nano-toxin. In general, in the current study, the nano-toxin exhibit an inhibitory effect on the viability of breast cancer cells through apoptosis, which suggests that AgNPs could be used as a delivery system for targeting of toxins to cancer cells.     

Responses of wheat plants to interactions of 24-epibrassinolide and <Emphasis Type="Italic">Glomus mosseae</Emphasis> in saline condition

This study was designed to investigate the possible effects of 24-Epibrassinolide (BR), arbuscular mycorrhizal (AM) fungus, Glomus mosseae, singularly and collectively under salt stress in wheat (Triticum aestivum L.) plants. After foliar spraying of mycorrhizal and non-mycorrhizal plants by 5 µM epibrassinolide (24-Epi), they were treated with 0 and 150 mM NaCl for 2 weeks and then harvested. The results showed interactions of G. mosseae and 24-Epi could alleviate the adverse effects of salinity by improving relative water content (RWC) of leaves (62%), relative growth rate (40.74%), shoot fresh weights (39.83%) and shoot phosphorous content (63.93%), stimulating leaf enzymatic antioxidant activities including catalase (2.24 fold) and ascorbate peroxidase (2.18 fold) as well as malondialdehyde (36.17%) and H₂O₂ concentrations (49.74%) as compared to those of NaCl treatments. Moreover, mycorrhizal dependency of root dry weight (2%) and phosphorus concentration (0.4%) increased with AM infection and 24-Epi application under saline condition. Leaf RWC, also, negatively correlated with membrane electrolyte leakage. Furthermore, the greatest mitigating effects were observed in mycorrhizal plants subjected to NaCl and 24-Epi. This study indicated that 24-Epi application and AM fungi may synergistically mitigate harmful impacts of salinity in wheat plants.     

Synchronization of follicular wave emergence prior to superovulation in Bactrian camel (Camelus bactrianus)

This study was conducted to synchronize follicle wave emergence prior to superovulation using either GnRH or progestogen treatments, in Bactrian camels. GnRH group camels (n=5) received 20 microg of the GnRH analogue Buserelin on Days -18 and -4 of the experiment (initiation of superovulation=Day 0). Camels in the progestogen group (n=5) received two consecutive treatments of progestogens, 7 days apart, on Days -14 and -8 of the experiment. On each occasion, each female received three norgestomet implants and 200mg progesterone (i.m.) and all implants were removed 14 days after the first progestogen treatment coinciding with Day -1 of superovulation. A combination of eCG and FSH was used to induce superovulation and the growth of all subsequent follicles and CLs were monitored daily by ultrasonography. Following the first GnRH injection, mature follicles ovulated within 1-2 days, and a new follicle wave emerged after 3+/-0.77 days. At the time of the second GnRH injection, a mature follicle (15.6+/-0.97 mm) ovulated and a new follicular wave emerged between 1 and 2 days after GnRH injection. Growing follicles at the time of the first progestogen treatment became either atretic (n=1) or persistent (n=4) and a new follicle wave (n=3) emerged 3-6 days later. At the initiation of superovulation, the diameters of the largest follicle in GnRH and progestogen groups were 7.4+/-0.59 and 20.5+/-2.26 mm, respectively but after superovulation and mating there was no significant differences in the number of unovulated follicles or CLs between groups. In conclusion, two GnRH injections, 14 days apart, may be used to synchronize follicle wave emergence in Bactrian camel.     

The Effects of Probiotics or Synbiotics Supplementation in Women with Polycystic Ovarian Syndrome: a Systematic Review and Meta-Analysis of Randomized Clinical Trials

Probiotics and Antimicrobial Proteins - We searched bibliographic databases from inception through May 2018 to evaluate the effect of probiotics (or synbiotics) supplementation in women suffering...     

Identification of novel azaindazole CCR1 antagonist clinical candidates

Exploring various cyclization strategies, using a submicromolar pyrazole HTS screening hit 6 as a starting point, a novel indazole based CCR1 antagonist core was discovered. This report presents the design and SAR of CCR1 indazole and azaindazole antagonists leading to the identification of three development compounds, including 19e that was advanced to early clinical trials.