Metformin, an oral anti-diabetic drug, is known to possess a powerful antitumor effect by modulating the tumor-immune interaction. The precise influence of metformin on natural killer (NK) cells, a ...crucial innate immunity player, is not completely understood. In our study, analyses of the effect of metformin on the NK cell functional phenotype were performed, and the potential mechanisms underlying it were investigated.
BALB/C wild type mice were treated with metformin, and the functional phenotype of splenocytes and potential underlying mechanisms were investigated.
Metformin significantly boosts NK cell cytotoxicity and the percentage of NKp46
, FasL
, and interferon (IFN)-γ
NK cells while decreasing interleukin (IL)-10 producing NK cells. Our research also demonstrated that the simultaneous administration of metformin and 1-methyl-DL-tryptophan (1-MT), a specific inhibitor of indoleamine 2,3-dioxygenase (IDO), significantly increased the NK cells synthesis of IFN-γ, IL-17, perforin, and FasL and NKp46 expression. These findings imply that metformin potentiates NK cell cytotoxicity through mechanisms other than IDO blockade. Metformin administration strongly increased the expression of immunostimulatory microRNA (miRNA)-150 and miRNA-155, while decreasing the expression of immunosuppressive miRNA-146a.
These findings suggest that metformin can directly potentiate NK cell activation and cytotoxicity. This research may contribute to dissecting key mechanisms of metformin exerting antitumor activity to advance the use of metformin as an antitumor agent.
Treatment of psoriasis is very complex and there are no still universal, nor unique treatment modalities. Apart from conventional treatment, which includes topical calcipotriol (vitamin D3 analogue), ...balneotherapy is drawing increased attention worldwide. Being part of climatotherapy, balneotherapy is defined as the use of natural environmental factors in the treatment of health conditions, whereas in the treatment of psoriasis it means the use of mineral baths and peloids. The aim of this study was to examine the therapeutic efficacy of mineral waters and peloids of the Rusanda Spa on plaque psoriasis in patients also treated with calcipotriol.
The study included 60 patients divided into two groups. The first group included patients treated with mineral waters, peloids and calcipotriol in the Rusanda Spa, while the second one included those treated only with calcipotriol. The study took 21 days, and each patient was followed up for at least one month after ending the treatment. The treatment efficacy was measured by psoriasis area severity index (PASI) scores on the days 0, 7, 14 and 21 during the treatment and 30 after the end of the therapy.
After a 3-week treatment in the Rusanda Spa, the first group showed a decrease in PASI score by 59.45%, whereas in the group of outpatients treated by calcipotriol it was 39.34%. On the day 30 following the treatment, the first group presented with the PASI score reduction of 58.44%, and the second group of 34.78%. The therapeutic efficacy of mineral waters and peloids combined with calcipotriol showed to be significantly higher in regard to monotherapy with calcipotriol (p < 0.05). In regard to clinical symptoms, the best results were obtained in the reduction of desquamation (p < 0.001).
The results of our study show that in the treatment of plaque-type psoriasis, topical calcipotriol combined with Spa Rusanda balineotherapy is more effective than topical calcipotriol alone. Randomized controlled trials are needed to confirm the effects of balneotherapy as monotherapy in treatment of this type of psoriasis.
As a non-Annex I Party to the United Nations Framework Convention on Climate Change and Kyoto Protocol signatory, the Republic of Serbia has committed to develop GHG (Greenhouse Gases) emission ...inventory and prepare comprehensive program of mitigation measures at national level.
The paper presents results of 2000–2008 GHG emission inventory assembled for PDH (Public District Heating) sub-sector in accordance with revised IPCC (Intergovernmental Panel on Climate Change) Tier 1 methodology. Evaluation of proposed mitigation measures was performed based on 2012 and 2015 GHG emission projections, obtained for basic and four alternative scenarios, all characterized by the same energy demand but with different fuel mix used. The first alternative scenario addresses GHG emissions in case that solid fuel is substituted by natural gas. The second alternative scenario represents a sub-scenario of the first alternative scenario, with additional substitution of liquid fuel with locally available biomass. Third alternative scenario addresses emissions resulting from complete fuel switch from natural gas to liquid fuel oil, while the final alternative scenario considers the case when natural gas is the only energy resource used.
GHG emission trends in the period until 2015, examined in case of previously mentioned basic and four alternative scenarios, point out to the positive impact of fuel switch on GHG emission reduction and pathways for future implementation of proposed mitigation measures. Results obtained clearly quantified assumption that fuel substitution by locally available biomass could solve environmental problems, overcome problems associated with high prices of imported fuels, improve energy supply security and increase local employment.
Galectin-3 (Gal-3), multifunctional protein plays important roles in inflammatory response, infection and fibrosis. The goal of study was to determine the association of Gal-3, immune response, ...clinical, biochemical, and radiographic findings with COVID-19 severity. Study included 280 COVID-19 patients classified according to disease severity into mild, moderate, severe and critical group. Cytokines, clinical, biochemical, radiographic data and peripheral blood immune cell make up were analyzed. Patients in critical group had significantly higher serum level of Gal-3, IL-1β, TNF-α, IL-12, IL-10 compared to the patients in less severe stages of disease. Strong positive correlation was detected between Gal-3 and IL-1β, moderate positive correlation between Gal-3, TNF-α and IL-12, moderate negative correlation between Gal-3, IL-10/IL-1β and IL-10/TNF-α. Moderate positive correlation noted between Gal-3 and urea, D dimer, CXR findings. Strong negative correlation detected between Gal-3 and p0
, Sa0
and moderate negative correlation between Gal-3, lymphocyte and monocyte percentage. In the peripheral blood of patients with more severe stages of COVID-19 we detected significantly increased percentages of CD56
CD3
TNF-α
T cells and CD56
CD3
Gal-3
T cells and increased expression of CCR5 in PBMCs. Our results predict Gal-3 as an important marker for critical stage of COVID-19. Higher expression of Gal-3, TNF-α and CCR5 on T cells implicate on promoting inflammation and more severe form of disease.
Metformin, a medication known for its anti-glycemic properties, also demonstrates potent immune system activation. In our study, using a 4T1 breast cancer model in BALB/C WT mice, we examined ...metformin’s impact on the functional phenotype of multiple immune cells, with a specific emphasis on natural killer T (NKT) cells due to their understudied role in this context. Metformin administration delayed the appearance and growth of carcinoma. Furthermore, metformin increased the percentage of IFN-γ+ NKT cells, and enhanced CD107a expression, as measured by MFI, while decreasing PD-1+, FoxP3+, and IL-10+ NKT cells in spleens of metformin-treated mice. In primary tumors, metformin increased the percentage of NKp46+ NKT cells and increased FasL expression, while lowering the percentages of FoxP3+, PD-1+, and IL-10-producing NKT cells and KLRG1 expression. Activation markers increased, and immunosuppressive markers declined in T cells from both the spleen and tumors. Furthermore, metformin decreased IL-10+ and FoxP3+ Tregs, along with Gr-1+ myeloid-derived suppressor cells (MDSCs) in spleens, and in tumor tissue, it decreased IL-10+ and FoxP3+ Tregs, Gr-1+, NF-κB+, and iNOS+ MDSCs, and iNOS+ dendritic cells (DCs), while increasing the DCs quantity. Additionally, increased expression levels of MIP1a, STAT4, and NFAT in splenocytes were found. These comprehensive findings illustrate metformin’s broad immunomodulatory impact across a variety of immune cells, including stimulating NKT cells and T cells, while inhibiting Tregs and MDSCs. This dynamic modulation may potentiate its use in cancer immunotherapy, highlighting its potential to modulate the tumor microenvironment across a spectrum of immune cell types.
The technical analysis of a hybrid wind-photovoltaic energy system with
hydrogen gas storage was studied. The market for the distributed power
generation based on renewable energy is increasing, ...particularly for the
standalone mini-grid applications. The main design components of PV/Wind
hybrid system are the PV panels, the wind turbine and an alkaline
electrolyzer with tank. The technical analysis is based on the transient
system simulation program TRNSYS 16. The study is realized using the
meteorological data for a Typical Metrological Year (TMY) for region of Novi
Sad, Belgrade cities and Kopaonik national park in Serbia. The purpose of the
study is to design a realistic energy system that maximizes the use of
renewable energy and minimizes the use of fossil fuels. The reduction in the
CO2 emissions is also analyzed in the paper.
In today’s rapidly evolving technological landscape, effective management of information technology (IT) projects is paramount for organizational success. However, ensuring sustainability in IT ...project management remains a persistent challenge. This paper proposes a novel approach centered on data-driven strategies to enhance sustainability and excellence in IT project management. By harnessing the power of data analytics, organizations can derive actionable insights to optimize resource allocation, mitigate risks, and streamline project workflows. The integration of data-driven decision making processes enables project managers to make informed choices, fostering adaptability and resilience in the face of dynamic project environments. This research explores the utilization of IT software project performance metrics and historical project data to fuel analysis of how strategies drive business sustainability. Moreover, this paper examined these dimensions with the help of advanced analytics techniques such as multiple linear regression. By aligning IT project management practices with business sustainability objectives, organizations can enhance project success rates, while minimizing adverse environmental impacts and resource consumption. Prospectively, this kind of research should expand to determining factors for the adoption of data-driven strategies to empower organizations to achieve sustainable IT project management excellence, ensuring long-term competitiveness and value creation in a digitalized world.
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