Protective Influence of SGLT-2 Inhibitors Against Heart Failure in Type 2 Diabetes Mellitus Through Longitudinal Clinical Database Analysis.

: Sodium-glucose co-transporter 2 (SGLT-2) inhibitors, initially designed for type 2 diabetes, promote glucose excretion and lower blood glucose. Newer analogs like empagliflozin and dapagliflozin improve cardiovascular outcomes through mechanisms other than glycemic control, including blood pressure reduction and anti-inflammatory effects. Given the high cardiovascular risk present in diabetes, our study aims to emphasize the cardioprotective benefits of SGLT-2 inhibitors as a preventive therapy for heart failure (HF) in high-risk T2DM patients.

Understanding the effects of weather parameters on the population dynamics of an endangered geophyte supports monitoring efficiency.

Due to their complex life cycles geophytes are often neglected in conservation programs, despite they are important elements of early spring communities. Their life cycle is strongly affected by weather parameters, i.e.

Werner helicase interacting protein 1 contributes to G-quadruplex processing in human cells.

Genome replication is frequently impeded by highly stable DNA secondary structures, including G-quadruplex (G4) DNA, that can hinder the progression of the replication fork. Human WRNIP1 (Werner helicase Interacting Protein 1) associates with various components of the replication machinery and plays a crucial role in genome maintenance processes. However, its detailed function is still not fully understood.

The ecological footprint of outdoor activities: Factors affecting human-vectored seed dispersal on clothing.

In the Anthropocene, humans are among the most abundant long-distance seed dispersal vectors globally, due to our increasing mobility and the growing global population. However, there are several knowledge gaps related to the process of human-vectored dispersal (HVD) on clothing. In a multi-site field experiment covering various habitat types in three countries of Central-Europe, we involved 88 volunteer participants and collected 251 HVD samples and 2008 subsamples from their socks and shoes.

Environmental heterogeneity increases the conservation value of small natural features in karst landscapes.

Local biodiversity hotspots are often located within regions where extreme and variable environmental - e.g., climatic and soil - conditions occur.

The hEag1 K Channel Inhibitor Astemizole Stimulates Ca Deposition in SaOS-2 and MG-63 Osteosarcoma Cultures.

The hEag1 (Kv10.1) K channel is normally found in the brain, but it is ectopically expressed in tumor cells, including osteosarcoma. Based on the pivotal role of ion channels in osteogenesis, we tested whether pharmacological modulation of hEag1 may affect osteogenic differentiation of osteosarcoma cell lines.

Vertical distribution of soil seed bank and the ecological importance of deeply buried seeds in alkaline grasslands.

Background: Soil seed banks play a central role in vegetation dynamics and may be an important source of ecological restoration. However, the vast majority of seed bank studies examined only the uppermost soil layers (0-10 cm); hence, our knowledge on the depth distribution of seed bank and the ecological significance of deeply buried seeds is limited. The aim of our study was to examine the fine-scale vertical distribution of soil seed bank to a depth of 80 cm, which is one of the largest studied depth gradients so far.

Vicinal difunctionalization of carbon-carbon double bond for the platform synthesis of trifluoroalkyl amines.

Regioselective vicinal diamination of carbon-carbon double bonds with two different amines is a synthetic challenge under transition metal-free conditions, especially for the synthesis of trifluoromethylated amines. However, the synthesis of ethylene diamines and fluorinated amine compounds is demanded, especially in the pharmaceutical sector. Herein, we demonstrate that the controllable double nucleophilic functionalization of an activated alkene synthon, originated from a trifluoropropenyliodonium salt with two distinct nucleophiles, enables the selective synthesis of trifluoromethylated ethylene amines and diamines on broad scale with high efficiency under mild reaction conditions.

Mgs1 protein supports genome stability via recognition of G-quadruplex DNA structures.

The integrity of the genetic material is crucial for every organism. One intrinsic attack to genome stability is stalling of the replication fork which can result in DNA breakage. Several factors, such as DNA lesions or the formation of stable secondary structures (eg, G-quadruplexes) can lead to replication fork stalling.

Periodic Membrane Potential and Ca Oscillations in T Cells Forming an Immune Synapse.

The immunological synapse (IS) is a specialized contact area formed between a T cell and an antigen presenting cell (APC). Besides molecules directly involved in antigen recognition such as the TCR/CD3 complex, ion channels important in the membrane potential and intracellular free Ca concentration control of T cells are also recruited into the IS. These are the voltage-gated Kv1.

The DNA-binding box of human SPARTAN contributes to the targeting of Polη to DNA damage sites.

Inappropriate repair of UV-induced DNA damage results in human diseases such as Xeroderma pigmentosum (XP), which is associated with an extremely high risk of skin cancer. A variant form of XP is caused by the absence of Polη, which is normally able to bypass UV-induced DNA lesions in an error-free manner. However, Polη is highly error prone when replicating undamaged DNA and, thus, the regulation of the proper targeting of Polη is crucial for the prevention of mutagenesis and UV-induced cancer formation.

The strong in vivo anti-tumor effect of the UIC2 monoclonal antibody is the combined result of Pgp inhibition and antibody dependent cell-mediated cytotoxicity.

P-glycoprotein (Pgp) extrudes a large variety of chemotherapeutic drugs from the cells, causing multidrug resistance (MDR). The UIC2 monoclonal antibody recognizes human Pgp and inhibits its drug transport activity. However, this inhibition is partial, since UIC2 binds only to 10-40% of cell surface Pgps, while the rest becomes accessible to this antibody only in the presence of certain substrates or modulators (e.

Epstein-Barr virus (HHV-4) inoculation to rabbits by intranasal and oral routes results in subacute and/or persistent infection dissimilar to human disease.

Objective: We report the infection of New Zealand white rabbits with Epstein-Barr virus (EBV).

Methods: EBV prepared in B95-8 (producer) cells was inoculated to rabbits by combined intranasal and oral routes. Blood and white blood cell (WBC) samples were taken before infection, then on days 8, 28 and 98 post-infection (p.

Margatoxin is a non-selective inhibitor of human Kv1.3 K+ channels.

Margatoxin (MgTx), an alpha-KTx scorpion toxin, is considered a selective inhibitor of the Kv1.3K + channel. This peptide is widely used in ion channel research; however, a comprehensive study of its selectivity with electrophysiological methods has not been published yet.

Acceptability of less than perfect health states in rheumatoid arthritis: the patients' perspective.

Some health problems are considered by many individuals as a 'normal' part of ageing. Our aim was to investigate whether patients with rheumatoid arthritis (RA) consider different types and levels of health losses as acceptable beyond a certain age. A multicenter cross-sectional survey was performed involving RA patients at the initiation of the first biological therapy.

Short communication: role of Mycoplasma arginini in mastitis caused by Streptococcus dysgalactiae.

We performed a comparative study on the development of mastitis induced by Mycoplasma arginini or Streptococcus dysgalactiae after challenging the cows. Mycoplasma arginini did not cause any clinical symptoms on its own, resulting in only a transient increase of somatic cell count (SCC; increase ranging from 0.5 × 10(6) to 0.

Successful unrelated umbilical cord blood transplantation in Lesch-Nyhan syndrome.

Lesch-Nyhan syndrome (LNS) is a chronic, progressive neurodevelopmental disorder causing motor and behavioral dysfunction due to decreased synthesis of the enzyme hypoxantine-guanine phosphoribosyltransferase (HPRT). Affected boys have mental retardation, delayed development, extrapyramidal motor disturbances and self-injuring behavior. As hematopoietic stem cell transplantation (HSCT) has been shown to be effective in several neurodevelopmental inborn errors, we hypothesized that it could be favorable in LNS as well.

[Growth hormone receptor antagonist in the treatment of acromegaly].

Exploration of construction, function and interaction of human growth hormone and growth hormone receptor in details resulted in the innovation of the new growth hormone receptor antagonist, pegvisomant. Pegvisomant with different mechanism of action extended the tools of medical management of acromegaly. Importance of the novel treatment modality is high.

Pgp inhibition by UIC2 antibody can be followed in vitro by using tumor-diagnostic radiotracers, 99mTc-MIBI and 18FDG.

P-glycoprotein (Pgp, ABCB1) is one of the active efflux pumps that are able to extrude a large variety of chemotherapeutic drugs from the cells, causing the phenomenon of multidrug resistance. It has been shown earlier that the combined application of a class of Pgp modulators (e.g.

Daunorubicin and doxorubicin inhibit the [(11)C]choline accumulation in cancer cells.

We studied how very short (10-40min) incubation with anthracycline derivatives modifies the accumulation of PET tumor-diagnostic radiotracers in cancer cells. The human ovarian A2780 and A2780AD, human B lymphoid JY, human epidermoid KB-3-1 and KB-V-1, and smooth muscle DDT1 MF-2 cells were pre-incubated with daunorubicin and doxorubicin, and the uptake of [(18)F]FDG and [(11)C]choline was measured. Anthracycline treatment decreased remarkably the [(11)C]choline accumulation in a concentration dependent manner, while it did not modify significantly the [(18)F]FDG uptake of the cells.

Functional consequences of Kv1.3 ion channel rearrangement into the immunological synapse.

Formation of immunological synapse (IS), the interface between T cells and antigen presenting cells, is a crucial step in T cell activation. This conjugation formation results in the rearrangement and segregation of a set of membrane bound and cytosolic proteins, including that of the T cell receptor, into membrane domains. It was showed earlier that Kv1.

Potassium channel expression in human CD4+ regulatory and naïve T cells from healthy subjects and multiple sclerosis patients.

The membrane potential of human T cells is regulated by two potassium channels: the voltage-gated K(V)1.3 and the Ca2+-activated K(Ca)3.1.