Search

Background: Kidney transplantation is followed by immunosuppressive therapy involving calcineurin inhibitors (CNIs) such as cyclosporin A. However, long-term high CNIs doses can lead to vitamin D deficiency, and genetic variations influencing vitamin D levels can indirectly impact the necessary CNIs dosage. This study investigates the impact of genetic variations of vitamin D binding protein (DBP) rs2282679 and CYP2R1 hydroxylase rs10741657 polymorphisms on the cyclosporin A dosage in kidney transplant recipients. Additional polymorphisims of genes that are predicted to influence the pharmacogenetic profile were included. Methods: Gene polymorphisms in 177 kidney transplant recipients were analyzed using data mining techniques, including the Random Forest algorithm and Classification and Regression Trees (C&RT). The relationship between the concentration/dose (C/D) ratio of cyclosporin A and genetic profiles was assessed to determine the predictive value of DBP rs2282679 and CYP2R1 rs10741657 polymorphisms. Results: Polymorphic variants of the DBP (rs2282679) demonstrated a strong predictive value for the cyclosporin A C/D ratio in post-kidney transplantation patients. By contrast, the CYP2R1 polymorphism (rs10741657) did not show predictive significance. Additionally, the immune response genes rs231775 CTLA4 and rs1800896 IL10 were identified as predictors of cyclosporin A response, though these did not result in statistically significant differences. Conclusions:DBP rs2282679 polymorphisms can significantly predict the cyclosporin A C/D ratio, potentially enhancing the accuracy of CNI dosing. This can help identify patient groups at risk of vitamin D deficiency, ultimately improving the management of kidney transplant recipients. Understanding these genetic influences allows for more personalized and effective treatment strategies, contributing to better long-term outcomes for patients. [ABSTRACT FROM AUTHOR]

Osteoporosis is a multifactorial systemic skeletal disease that is characterized by a low bone mineral density (BMD) and the microarchitectural deterioration of bone tissue, leading to bone fragility. The search for new genes that may play an important role in the regulation of bone mass and the development of osteoporosis is ongoing. Recently, it was found that altering the activity of the endothelin-1-converting enzyme encoded by the ECE1 gene may affect bone mineral density (BMD). Another gene involved in the process of osteoblast differentiation and maturation is believed to be PPARG (peroxisome proliferator-activated receptor gamma). This participates in regulating the transformation of stem cells and affects the process of bone formation and resorption. Therefore, we analyzed the association of the ECE1 and PPARG variants with osteopenia and osteoporosis risk in the Polish population. This study included a group (n = 608) of unrelated Polish women (245 individuals with osteoporosis (aged: 57 ± 9), 109 individuals with osteopenia (aged: 53 ± 8) and 254 healthy controls (aged: 54 ± 8)). The real-time PCR technique was used to determine the genetic variants for rs213045 (-338G>T) and rs213046 (-839A>C) of the ECE1 gene and rs1801282 (Pro12Ala, C>G) of the PPARG gene. Analysis of the PPARG rs1801282 variants did not show any association with the risk of osteoporosis and osteopenia. However, in the densitometric results, lower median Z-score values were observed for the T allele compared to the G allele for the rs213045 variant of the ECE1 gene (−1.11 ± 1.07 vs. −0.78 ± 1.21, p = 0.021). Moreover, the TT genotype for the rs213045 variant was more common in women with osteopenia (13.8%, OR = 2.82, p < 0.05) and osteoporosis (7.8%, OR = 1.38, p > 0.05) compared to the control group (5.5%). Additionally, our results suggested that the T allele of rs213045 was more common in women with osteopenia compared to the controls. We further observed that the haplotype containing two major GA alleles of ECE1 (rs213045, rs213046) could reduce the risk of osteopenia in our population. Finally, we found that women with osteoporosis had statistically significantly lower body mass and BMI values compared to the control group. Our results suggest that the ECE1 rs213045 variant may increase the risk of osteopenia. However, the data obtained require confirmation in further studies. [ABSTRACT FROM AUTHOR]

The FUT2 gene encodes an enzyme called α-1,2-fucosyltransferase, which is involved in the formation of blood group antigens AB0(H) and is also involved in the processes of vitamin B12 absorption and its transport between cells. FUT2 gene polymorphisms are associated with vitamin B12 levels in the body. Vitamin B12 deficiency associated with hyperhomocysteinemia is a major risk factor for cardiovascular diseases (CVDs), which are one of the main causes of death in patients after kidney transplantation. The aim of our study was to determine the impact of the rs602662 (G>A) polymorphism of the FUT2 gene on the functionality of transplanted kidneys and the risk of CVD in patients after kidney transplantation. The study included 402 patients treated with immunosuppression (183 patients taking cyclosporine (CsA) and 219 patients taking tacrolimus (TAC)). The analysis of the FUT2 rs602662 (G>A) polymorphism was performed using real-time PCR. Patients with CsA were more likely to be underweight (1.64% vs. 0.91%) and obese (27.87% vs. 15.98%), while those taking TAC were more likely to be of normal weight (39.27%) or overweight (43.84%). No statistically significant differences were observed comparing the mean blood pressure, both systolic and diastolic. The renal profile showed a higher median urea nitrogen concentration in patients with CsA (26.45 mg/dL (20.60–35.40) vs. 22.95 mg/dL (17.60–33.30), p = 0.004). The observed frequency of rs602662 alleles of the FUT2 gene was similar in the analyzed groups. The A allele was present in 43.7% of patients with CsA and 41.1% of those taking TAC (OR = 0.898; 95% CI: 0.678–1.189; p = 0.453). In the group with CsA, the GG genotype was present in 32.2% of patients, the GA in 48.1% and the AA in 19.7%. A similar distribution was obtained in the TAC group: GG—33.8%, GA—50.2%, and AA—16.0%. An association of genotypes containing the G allele with a higher incidence of hypertension was observed. The G allele was present in 65% of people with hypertension and in 56% of patients with normal blood pressure (p = 0.036). Moreover, the evaluation of the renal parameters showed no effect of the FUT2 polymorphism on the risk of organ rejection because the levels of creatinine, eGFR, potassium, and urea nitrogen were prognostic of successful transplantation. Our results suggest that the rs6022662 FUT2 polymorphism may influence the risk of cardiovascular diseases. [ABSTRACT FROM AUTHOR]

CAR-T immunotherapy, based on the genetic modification of T lymphocytes that contain a chimeric antigen receptor (CAR), has been a major breakthrough in the treatment of cancer patients since the 2017 approval of Kymriah™ (tisagenlecleucel) by the United States Food and Drug Administration (FDA). To date, six CAR-T cell therapies have been approved by the FDA, showing efficacy in patients with B-cell cancers and multiple myeloma. However, adverse events, such as cytokine release syndrome and neurotoxicity, present serious challenges to successful CAR-T cell therapy. The severity of adverse events correlates with the degree of tumor burden before treatment. This observation is supported by the use of CD19-specific CAR-T cells in autoimmune diseases such as systemic lupus erythematosus and anti-synthetase syndrome. These results indicate that early initiation of CAR-T cell therapy with a low tumor burden, or the use of a tumor-shrinking strategy prior to CAR-T cell infusion, may reduce the severity of adverse events. CAR-T cell therapy is expensive and has limited efficacy in solid tumors. Research is currently under way to increase the effectiveness of CAR-T therapy in patients with solid tumors not responding to conventional treatment. [ABSTRACT FROM AUTHOR]

The purpose of the study was to conduct a pilot survey of respondents’ preferences for the culinary use of legumes (broad bean crops) in terms of their healthpromoting properties. The survey was conducted among 120 people, 2021 nationwide, electronically using a Google form. Based on the survey, it was found that respondents rarely consume legumes, but are aware of their high nutritional and health-promoting value. The main motive for eating them is sensory acceptance (taste) and the possibility of preparing a variety of dishes. The most common dish prepared from legume seeds was baked beans, bean soup or the use of cooked seeds as an addition to vegetable salads. Among the health-promoting properties of legumes, respondents most often cited intestinal regulation, low glycemic index, prevention of heart disease and atherosclerosis. [ABSTRACT FROM AUTHOR]

Inflammation is the critical component of neuropathic pain; therefore, this study aimed to assess the potential anti-inflammatory effects of Cannabis sativa L. extracts in a vincristine-induced model of neuropathic pain. The effects of different doses (5.0-40.0 mg/kg) of two Cannabis sativa L. extracts (B and D) on COX-1, COX-2, TNF-α, and NF-κB mRNA and protein levels were examined in the rat hippocampus, cerebral cortex, and blood lymphocytes. There were statistically significant differences in COX-1, COX-2, and TNF-α mRNA and protein expression in the hippocampus and cerebral cortex, with significant differences in COX-2 and TNF-α in the lymphocytes. Extract D dose-dependently increased COX-1 mRNA and protein in the hippocampus and cortex. In contrast, Extract B dose-dependently increased COX-1 mRNA and decreased COX-2 mRNA (in a dose of 7.5 mg/kg) and TNF-α protein levels in the cortex. Cannabis sativa L. extracts significantly influenced the expression of inflammatory genes and proteins, with effects varying based on dose and tissue type. The increased expression of COX-1, COX-2, and TNF-α (in comparison to groups receiving NaCl, vincristine, and gabapentin) in the rat hippocampus and COX-1 in the cerebral cortex suggests that Cannabis may have a pro-inflammatory effect. Due to species specificity, the results of our research based on rats require confirmation in humans. However, Cannabis sativa should be recommended with caution for treating pain with an inflammatory component.