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Background: The present study investigated the outcomes and possible predictive factors of autologous bone marrow cells (BMCs) therapy in patients with "no-option" critical limb ischaemia (CLI). It was focused on exploring the clinical background and prior statin and renin-angiotensin system (RAS)-acting agents pharmacotherapy related to the therapeutic efficacy of BMCs treatment. Methods: In the present study, we reviewed thirty-three patients (mean age 64.9 ± 10 years; 31 males) with advanced CLI after failed or impossible revascularisation, who were treated with 40 mL of autologous BMCs by local intramuscular application. Patients with limb salvage and wound healing (N = 22) were considered as responders to BMCs therapy, and patients with limb salvage and complete ischemic wound healing (N = 13) were defined as super-responders. Logistic regression models were used to screen and identify the prognostic factors, and a receiver operating characteristics (ROC) curve, a linear regression, and a survival curve were drawn to determine the predictive accuracy, the correlation between the candidate predictors, and the risk of major amputation. Results: Based on the univariate regression analysis, baseline C-reactive protein (CRP) and transcutaneous oxygen pressure (TcPO2) values were identified as prognostic factors of the responders, while CRP value, ankle-brachial index (ABI), and bone marrow-derived mononuclear cells (BM-MNCs) concentration were identified as prognostic factors of the super-responders. An area under the ROC curve of 0.768 indicated good discrimination for CRP > 8.1 mg/L before transplantation as a predictive factor for negative clinical response. Linear regression analysis revealed a significant dependence between the levels of baseline CRP and the concentration of BM-MNCs in transplanted bone marrow. Patients taking atorvastatin before BMCs treatment (N = 22) had significantly improved TcPO2 and reduced pain scale after BMCs transplant, compared to the non-atorvastatin group. Statin treatment was associated with reduced risk for major amputation. However, the difference was not statistically significant. Statin use was also associated with a significantly higher concentration of BM-MNCs in the transplanted bone marrow compared to patients without statin treatment. Patients treated with RAS-acting agents (N = 20) had significantly reduced pain scale after BMCs transplant, compared to the non-RAS-acting agents group. Similar results, reduced pain scale and improved TcPO2, were achieved in patients treated with atorvastatin and RAS-acting agents (N = 17) before BMCs treatment. Results of the Spearman correlation showed a significant positive correlation between CLI regression, responders, and previous therapy before BMCs transplant with RAS-acting agents alone or with atorvastatin. Conclusions: CRP and TcPO2 were prognostic factors of the responders, while CRP value, ABI, and BM-MNCs concentration were identified as predictive factors of the super-responders. Atorvastatin treatment was associated with a significantly increased concentration of BM-MNCs in bone marrow concentrate and higher TcPO2 and lower pain scale after BMCs treatment in CLI patients. Similarly, reduced pain scales and improved TcPO2 were achieved in patients treated with atorvastatin and RAS-acting agents before BMCs treatment. Positive correlations between responders and previous treatment before BMCs transplant with RAS-acting agents alone or with atorvastatin were significant. [ABSTRACT FROM AUTHOR]

Currently published data suggest that the specific transcription factors GATA4 and MEF2C play a crucial role in the development of pathological cardiac hypertrophy. The synergistic effect of these two transcription factors was observed mainly with a calcineurin/NFAT signalling pathway that induces the expression of genes associated with hypertrophy. It is assumed that statins can affect the process of cardiac fibrosis and subsequent heart remodelling through cardioprotective pleiotropic effects, which are still not sufficiently examined. The aim of the study was to investigate the intervention of atorvastatin into molecular mechanisms of cardiac fibrosis and pathological cardiac hypertrophy by monitoring changes of the expression of selected genes in human cardiac fibroblasts (HCF) in vitro. Experimental cell cultures of HCF were treated with atorvastatin (10 µM) for 24 hr, 48 hr, and 72 hr. Changes in the expression of selected genes were assessed by RT-qPCR. Our findings reflect the occurrence of several changes in HCF after their treatment with atorvastatin. A significant reduction (p < .0001) was observed in the gene expression of the alpha-SMA, a major marker of the activated fibroblasts responsible for development of cardiac fibrosis. A significant decrease (p < .05) in gene expression of the transcription factors GATA4 and MEF2C was also observed, demonstrating a possible protective effect of atorvastatin against pathological cardiac hypertrophy. [ABSTRACT FROM AUTHOR]

The global pandemic caused by the SARS-COV2 virus persists. Coronaviruses causing COVID-19 disease interact with ACE-2 receptors and penetrate host cells by endocytosis. This process can lead to a rapid release of proinflammatory mediators, which is one of the factors responsible for the development of one serious complication of the disease, acute respiratory distress syndrome. The altered regulation of specific cytokines and growth factors that affect various physiological processes, such as immune responses, can exacerbate the progression of viral diseases and contribute to the pathogenesis of COVID-19 disease. The aim of this study was to compare relative expression of selected growth factors (IGF-1, FGF-2, VEGF-A) in plasma samples from patients with and without COVID-19 disease. To measure relative expression RT-qPCR was used. Our data showed that relative expressions of selected growth factors in 3 groups of patients (6 patients cured from the disease, 6 patients who succumbed to the disease, 6 COVID-19 negative patients) are altered. The relative expression of VEGF-A was increased in patients who died of COVID-19 disease. A decrease in the relative expression of FGF-2 was observed in patients who overcame the disease compared to patients who succumbed to the disease. Differences in relative expression of IGF-1 were very slight in all three patient groups. These changes all suggest the importance of examining specific growth factors and their levels in relation to the development of COVID-19 disease. [ABSTRACT FROM AUTHOR]

Cell therapy represents an innovative approach in treatment for many injuries. Stem cells can also be applied in dental treatment to regenerate bone tissue in the craniofacial region. It has been shown that vascular endothelial growth factor A (VEGFA) and hepatocyte growth factor (HGF) play an important role in this type of regeneration. However, due to complications such as pain, it is necessary to study the effect of pharmacotherapy used because of its potential influence on applied stem cells and subsequently molecular regenerative processes. The main goal of this work was to evaluate the effect of ibuprofen on human dental pulp stem cells (DPSC) in vitro and to identify relative mRNA expression levels of growth factors, VEGFA and HGF. DPSC in ninth passage was incubated with 300 µM ibuprofen for 24, 48, and 72 hr. Total RNA was extracted using phenol-chloroform extraction. The relative mRNA expression levels of VEGFA and HGF were measured by RT-qPCR method. Our preliminary data showed a significant increase in relative mRNA expression levels of VEGFA and HGF after influence of DPSC by ibuprofen at all time intervals. This suggests that the possible use of nonsteroidal anti-inflammatory drugs in parallel with cell therapy could be beneficial, but to confirm this phenomenon further research is needed. [ABSTRACT FROM AUTHOR]

Recently, the pleiotropic extraskeletal effects of vitamin D have received more attention in addition to its well-known importance for bone health. Research suggests that vitamin D deficiency is as associated with the risk of developing various malignancies. Increased expression of vitamin D receptors and vitamin D metabolism enzymes is observed in cancer cells. There is growing evidence that vitamin D exhibits anticancer activity via different pathways, for example, inhibition of proliferation or induction of cell apoptosis. The aim of this work was to evaluate the effect of vitamin D (in the form of cholecalciferol) on viability and relative expression of apoptosis regulators BAX and Bcl-2 in human cervical cancer cell line HeLa. Experimental cultures in eighth passage were treated with 1300 nM and 130 nM cholecalciferol for 24 hr. Viability of the cells was analysed by flow cytometry and relative expression of BAX and Bcl-2 proteins by western blotting. Our preliminary results showed that viability of HeLa cells after cholecalciferol treatment did not change significantly compared to the control condition. The amount of BAX protein decreased more in cholecalciferol-treated cells compared to the control condition, but no significant difference was observed. HeLa cells treated with cholecalciferol also indicated slight alteration in Bcl-2 expression and BAX/Bcl-2 ratio without statistical significance. In conclusion, the treatment of HeLa cells with cholecalciferol at the used concentrations did not have a significant effect on the apoptotic signalling pathway. [ABSTRACT FROM AUTHOR]

Pregnancy and postpartum period are associated with demanding physical and psychological changes that often lead to the development of psychological disorders. Depression is diagnosed in more than one in six women after childbirth. However, the prevalence of postpartum depression can be much higher because many cases are undiagnosed. In the case of severe depression, the patient is switched to pharmacological treatment, with sertraline being the most commonly used for this diagnosis. A new drug used in the treatment of postpartum depression is brexanolone, which was registered by FDA in 2019. The advantage over conventional therapy is its rapid onset of action. The structure represents the neuroactive steroid - allopregnanolone, which acts as an agonist on the &#948;-subunit of the GABA receptor and improves the symptoms of postpartum depression. In addition to the registered brexanolone, another steroidal drug, zuranolone, is available in the third phase of the clinical trial. The steroid structure was chemically altered to improve bioavailability and create an oral dosage form. Another synthetic analogue of neuroactive allopregnanolone, known as ganaxolone, did not show a significant reduction in depressive symptoms in the second phase of the clinical trial compared to placebo. Nevertheless, it has great therapeutic potential in the treatment of various types of epilepsy.