Although the application of medical marijuana and cannabinoid drugs is controversial, it is a part of modern-day medicine. The list of diseases in which cannabinoids are promoted as a treatment is constantly expanding. Cases of significant improvement in patients with a very poor prognosis of glioma or epilepsy have already been described. However, the occurrence of side effects is still difficult to estimate, and the current knowledge of the therapeutic effects of cannabinoids is still insufficient. In our opinion, the answers to many questions and concerns regarding the medical use of cannabis can be provided by pharmacogenetics. Knowledge based on proteins and molecules involved in the transport, action, and metabolism of cannabinoids in the human organism leads us to predict candidate genes which variations are responsible for the presence of the therapeutic and side effects of medical marijuana and cannabinoid-based drugs. We can divide them into: receptor genes—CNR1, CNR2, TRPV1, and GPR55, transporters—ABCB1, ABCG2, SLC6A, biotransformation, biosynthesis, and bioactivation proteins encoded by CYP3A4, CYP2C19, CYP2C9, CYP2A6, CYP1A1, COMT, FAAH, COX2, ABHD6, ABHD12 genes, and also MAPK14. This review organizes the current knowledge in the context of cannabinoids pharmacogenetics according to individualized medicine and cannabinoid drugs therapy.
Mechanistic understanding of the functionality of organic corrosion inhibitors in acidic media is essential to knowledge-based performance optimization. In this study, we address a key issue hindering progress in this area, namely the chemical nature of the corrosion inhibitor/substrate interface. X-ray photoelectron spectroscopy (XPS) is employed to reveal the surface termination of carbon-steel, following immersion in 1 M hydrochloric acid inhibited with 2mercaptobenzimidazole (MBI). Core level spectra indicate that the termination varies as a function of MBI concentration, with the interface consisting of MBI bound to film-free carbon-steel on highly inhibited substrates.
The efficacy of donor HSCT is partly reduced as a result of slow post-transplantation immune recovery. In particular, T cell regeneration is generally delayed, resulting in high infection-related mortality in the first years post-transplantation. Adoptive transfer of in vitro-generated human T cell progenitors seems a promising approach to accelerate T cell recovery in immunocompromised patients. AA may enhance T cell proliferation and differentiation in a controlled, feeder-free environment containing Notch ligands and defined growth factors. Our experiments show a pivotal role for AA during human in vitro T cell development. The blocking of NOS diminished this effect, indicating a role for the citrulline/NO cycle. AA promotes the transition of proT1 to proT2 cells and of preT to DP T cells. Furthermore, the addition of AA to feeder cocultures resulted in development of DP and SP T cells, whereas without AA, a preT cell-stage arrest occurred. We conclude that neither DLL4-expressing feeder cells nor feeder cell conditioned media are required for generating DP T cells from CB and G-CSF-mobilized HSCs and that generation and proliferation of proT and DP T cells are greatly improved by AA. This technology could potentially be used to generate T cell progenitors for adoptive therapy.
In this paper we demonstrate that patients treated with chemotherapy and/or hematopoietic stem cell transplantation (HSCT) have highly significant reduced serum ascorbic acid (AA) levels compared to healthy controls. We recently observed in in vitro experiments that growth of both T and NK cells from hematopoietic stem cells is positively influenced by AA. It might be of clinical relevance to study the function and recovery of immune cells after intensive treatment, its correlation to AA serum levels and the possible effect of AA supplementation.
A plasma source free from characteristic emission lines is described, based on laser irradiation of a water jet in a helium atmosphere. Various key aspects of the laser interaction are presented along with practical characterization of the observed isotropic approximately 4-10 keV x-ray emissions, measurements of which indicate subpicosecond duration. Observations are consistent with a vacuum heating plasma mechanism at the helium-water interface and indicate strong potential for in-house ultrafast chemical structure dynamics application when coupled to contemporary detector developments.
Therapeutic cancer vaccines show promise in preclinical studies, yet their clinical efficacy is limited. Increased recruitment of immune cells into tumors and suppression of the immune suppressive tumor environment are critical components toward effective cancer immunotherapies. Here, we report how local low-dose irradiation, alone or with a therapeutic immunization based on Semliki Forest virus (SFV) against human papillomavirus (HPV)-related cancer, influences these immune mechanisms. We first demonstrated that immunization with SFVeE6,7 or SFVeOVA, replicon particles expressing either HPV16 E6/E7 or ovalbumin, resulted in an antigen-specific migration of CD81 T cells into HPV-and OVA-specific tumors. Local low-dose tumor irradiation alone resulted in a 2-fold increase of intratumoral CD81 T cells. When 14 Gy irradiation was combined with immunization, intratumoral numbers of CD81 T cells increased 10-fold and the number of CD81 T cells specific for the E7-epitope increased more than 20-fold. Irradiation alone however also increased the number of intratumoral myeloid-derived suppressor cells (MDSCs) 3.5-fold. Importantly, this number did not further increase when combined with immunization. As a result, the ratio of antigen-specific CD81 T cells and MDSCs in tumors increased up to 85-fold compared to the control. We furthermore demonstrated that following irradiation CCR2 and CCL2, CXCR6 and CCL16, chemokines and ligands involved in tumor homing of immune cells, were significantly up regulated. This study demonstrates that local low-dose tumor irradiation influences the intratumoral immune population induced by SFVeE6,7 immunization by a strong increase in the ratio of antitumoral to immune suppressive cells, thus changing the intratumoral immune balance in favor of antitumor activity.An essential requirement for cancer immunotherapy is activation of antigen-specific T cells and their homing into tumors. Although antitumoral immunization studies in the clinic report the presence of vaccine-induced antigen-specific T cells in periphery or at the injection site, so far the therapeutic antitumor responses are limited. [1][2][3][4] The most obvious reasons for the lack of clinical responses can be insufficient tumor infiltration of antigen-specific immune effector cells and the immunosuppressive environment of the tumor. [5][6][7][8][9] Strategies aiming at promoting T-cell influx into the tumor or at reverting the immune suppression within the tumor microenvironment are currently the focus of numerous preclinical studies. In a recent review, we addressed various antitumoral therapeutic strategies currently under investigation.
It is well known that consumption of Brassica vegetables has beneficial effect on human's health. The greatest interest is focused on glucosinolates and their hydrolysis products isothiocyanates, due to their potential as cancer preventing compounds. Brassica vegetables are also rich in flavor compounds belonging to many chemical groups. The main sensory sensation related to these vegetable is their characteristic sharp and bitter taste, and unique aroma. Because of these features this group of vegetables is often rejected by consumers. Interestingly, for some people unpleasant sensations are not perceived, suggesting a potential role of inter-individual variability in bitter taste perception and sensibility. Receptors responsible for bitter sensation with the emphasis on Brassica are reviewed, as well as genetic predisposition for bitterness perception by consumers. Also the role of glucosinolates and isothiocyanates as compounds responsible for bitter taste is discussed based on data from the field of food science and molecular biology. Isothiocyanates are shown in broaded context of flavor compounds also contributing to the aroma of Brassica vegetables.
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