Catalytic sulfation of betulin with sulfamic acid : experiment and DFT calculation

Betulin is an important triterpenoid substance isolated from birch bark, which, together with its sulfates, exhibits important bioactive properties. We report on a newly developed method of betulin sulfation with sulfamic acid in pyridine in the presence of an Amberlyst(®)15 solid acid catalyst. It has been shown that this catalyst remains stable when being repeatedly (up to four cycles) used and ensures obtaining of sulfated betulin with a sulfur content of ~10%. The introduction of the sulfate group into the betulin molecule has been proven by Fourier-transform infrared, ultraviolet-visible, and nuclear magnetic resonance spectroscopy. The Fourier-transform infrared (FTIR) spectra contain absorption bands at 1249 and 835–841 cm(−1); in the UV spectra, the peak intensity decreases; and, in the nuclear magnetic resonance (NMR) spectra, of betulin disulfate, carbons С3 and С28 are completely shifted to the weak-field region (to 88.21 and 67.32 ppm, respectively) with respect to betulin. Using the potentiometric titration method, the product of acidity constants K(1) and K(2) of a solution of the betulin disulfate H(+) form has been found to be 3.86 × 10(–6) ± 0.004. It has been demonstrated by the thermal analysis that betulin and the betulin disulfate sodium salt are stable at temperatures of up to 240 and 220 °C, respectively. The density functional theory method has been used to obtain data on the most stable conformations, molecular electrostatic potential, frontier molecular orbitals, and mulliken atomic charges of betulin and betulin disulfate and to calculate the spectral characteristics of initial and sulfated betulin, which agree well with the experimental data

Assessment of Extremely Cold Subarctic Climate Environment Destruction of the Basalt Fiber Reinforced Epoxy (BFRE) Rebar Using Its Moisture Uptake Kinetics

A quite simple method is proposed for the assessment of extremely cold subarctic climate environment destruction of the basalt fiber reinforced epoxy (BFRE) rebar. The method involves the comparison of experimentally obtained long-term moisture uptake kinetic curves of unexposed and exposed BFRP rebars. A moisture uptake test was carried out at the temperature of 60 °C and relative humidity of 98 ± 2% for 306 days. The plasticization can be neglected because of low-level moisture saturation (<0.41% wt.); the swelling and structural relaxation of the polymer network can be neglected due to the high fiber content of BFRP rebar; moisture diffusion into the basalt fibers can be neglected since it is a much lesser amount than in the epoxy binder. These assumptions made it possible to build a three-stage diffusion model. It is observed that an increase in the density of defects with an increase in the diameter of the BFRP rebar is the result of the technology of manufacturing a periodic profile. The diffusion coefficient of the BFRP rebar with a 6, 10, or 18 mm diameter increased at an average of 82.7%, 56.7%, and 30%, respectively, after exposure to the climate of Yakutsk during 28 months, whereas it was known that the strength indicators had been increased

Calcification of Various Bioprosthetic Materials in Rats: Is It Really Different?

The causes of heart valve bioprosthetic calcification are still not clear. In this paper, we compared the calcification in the porcine aorta (Ao) and the bovine jugular vein (Ve) walls, as well as the bovine pericardium (Pe). Biomaterials were crosslinked with glutaraldehyde (GA) and diepoxide (DE), after which they were implanted subcutaneously in young rats for 10, 20, and 30 days. Collagen, elastin, and fibrillin were visualized in non-implanted samples. Atomic absorption spectroscopy, histological methods, scanning electron microscopy, and Fourier-transform infrared spectroscopy were used to study the dynamics of calcification. By the 30th day, calcium accumulated most intensively in the collagen fibers of the GA-Pe. In elastin-rich materials, calcium deposits were associated with elastin fibers and localized differences in the walls of Ao and Ve. The DE-Pe did not calcify at all for 30 days. Alkaline phosphatase does not affect calcification since it was not found in the implant tissue. Fibrillin surrounds elastin fibers in the Ao and Ve, but its involvement in calcification is questionable. In the subcutaneous space of young rats, which are used to model the implants’ calcification, the content of phosphorus was five times higher than in aging animals. We hypothesize that the centers of calcium phosphate nucleation are the positively charged nitrogen of the pyridinium rings, which is the main one in fresh elastin and appears in collagen as a result of GA preservation. Nucleation can be significantly accelerated at high concentrations of phosphorus in biological fluids. The hypothesis needs further experimental confirmation

Coronavirus-Specific Antibody and T Cell Responses Developed after Sputnik V Vaccination in Patients with Chronic Lymphocytic Leukemia

The clinical course of the new coronavirus disease 2019 (COVID-19) has shown that patients with chronic lymphocytic leukemia (CLL) are characterized by a high mortality rate, poor response to standard treatment, and low virus-specific antibody response after recovery and/or vaccination. To date, there are no data on the safety and efficacy of the combined vector vaccine Sputnik V in patients with CLL. Here, we analyzed and compared the magnitudes of the antibody and T cell responses after vaccination with the Sputnik V vaccine among healthy donors and individuals with CLL with different statuses of preexposure to coronavirus. We found that vaccination of the COVID-19–recovered individuals resulted in the boosting of pre-existing immune responses in both healthy donors and CLL patients. However, the COVID-19–naïve CLL patients demonstrated a considerably lower antibody response than the healthy donors, although they developed a robust T cell response. Regardless of the previous infection, the individuals over 70 years old demonstrated a decreased response to vaccination, as did those receiving anti-CD20 therapy. In summary, we showed that Sputnik V, like other vaccines, did not induce a robust antibody response in individuals with CLL; however, it provided for the development of a significant anti-COVID-19 T cell response

Food Xanthan Polysaccharide Sulfation Process with Sulfamic Acid

Xanthan is an important polysaccharide with many beneficial properties. Sulfated xanthan derivatives have anticoagulant and antithrombotic activity. This work proposes a new method for the synthesis of xanthan sulfates using sulfamic acid. Various N-substituted ureas have been investigated as process activators. It was found that urea has the greatest activating ability. BBD of xanthan sulfation process with sulfamic acid in 1,4-dioxane has been carried out. It was shown that the optimal conditions for the sulfation of xanthan (13.1 wt% sulfur content) are: the amount of sulfating complex per 1 g of xanthan is 3.5 mmol, temperature 90 °C, duration 2.3 h. Sulfated xanthan with the maximum sulfur content was analyzed by physicochemical methods. Thus, in the FTIR spectrum of xanthan sulfate, in comparison with the initial xanthanum, absorption bands appear at 1247 cm−1, which corresponds to the vibrations of the sulfate group. It was shown by GPC chromatography that the starting xanthan gum has a bimodal molecular weight distribution of particles, including a high molecular weight fraction with Mw > 1000 kDa and an LMW fraction with Mw < 600 kDa. It was found that the Mw of sulfated xanthan gum has a lower value (~612 kDa) in comparison with the original xanthan gum, and a narrower molecular weight distribution and is characterized by lower PD values. It was shown by thermal analysis that the main decomposition of xanthan sulfate, in contrast to the initial xanthan, occurs in two stages. The DTG curve has two pronounced peaks, with maxima at 226 and 286 °C

CX3CL1 and IL-15 Promote CD8 T cell chemoattraction in HIV and in atherosclerosis.

Atherosclerotic cardiovascular disease (ASCVD) remains an important cause of morbidity in the general population and risk for ASCVD is increased approximately 2-fold in persons living with HIV infection (PLWH). This risk is linked to elevated CD8 T cell counts that are abundant in atherosclerotic plaques and have been implicated in disease pathogenesis yet the mechanisms driving T cell recruitment to and activation within plaques are poorly defined. Here we investigated the role of CD8 T cells in atherosclerosis in a non-human primate model of HIV infection and in the HIV-uninfected elderly; we sought to identify factors that promote the activation, function, and recruitment to endothelium of CX3CR1+ CD8 T cells. We measured elevated expression of CX3CL1 and IL-15, and increased CD8 T cell numbers in the aortas of rhesus macaques infected with SIV or SHIV, and demonstrated similar findings in atherosclerotic vessels of HIV-uninfected humans. We found that recombinant TNF enhanced the production and release of CX3CL1 and bioactive IL-15 from aortic endothelial cells, but not from aortic smooth muscle cells. IL-15 in turn promoted CX3CR1 surface expression on and TNF synthesis by CD8 T cells, and IL-15-treated CD8 T cells exhibited enhanced CX3CL1-dependent chemoattraction toward endothelial cells in vitro. Finally, we show that CD8 T cells in human atherosclerotic plaques have an activated, resident phenotype consistent with in vivo IL-15 and CX3CL1 exposure. In this report, we define a novel model of CD8 T cell involvement in atherosclerosis whereby CX3CL1 and IL-15 operate in tandem within the vascular endothelium to promote infiltration by activated CX3CR1+ memory CD8 T cells that drive further endothelial activation via TNF. We propose that these interactions are prevalent in aging and in PLWH, populations where circulating activated CX3CR1+ CD8 T cell numbers are often expanded