The treatment of diabetes with new generation drugs

Introduction: Diabetes is a global problem, affecting nearly 422 million people around the world. Pathogenesis includes a defect in secretion or insulin activity. This results in an increase in the glucose level, which is associated with the development of complications. These include changes in peripheral vessels and nerves that lead to their damage. It is necessary to introduce appropriate treatment in the earliest stages of the disease to prevent these effects.Materials and methods: The aim of this work is to present knowledge about the treatment based on the recommendations of the Polish Diabetes Association, American Diabetes Association, as well as a literature review and analysis of publications published on PubMed and Google Scholar platforms.Results: Over the years, the recommendations and recommendations for treatment change. Recently, a greater role has been given to the latest antidiabetic drugs. This group includes SGLT-2 inhibitors as well as incremental drugs, the main representatives of which are GLP-1 analogues. These drugs affect the level of glycemia, but also have a beneficial effect on weight reduction and reduce the risk of cardiovascular events. Recently, Poland has introduced reimbursement of some new generation antidiabetic drugs such as dapaglyphosin, empaglyphosin and canaglyphosin.Conclusions: Dynamic development of diabetes treatment helps to slow down the course of the disease and postpones the introduction of insulin therapy as the final treatment method. Reimbursement of some antidiabetic drugs enables patients to have better access to drugs that have not been within their reach so far. The changes introduced are, in a way, groundbreaking in the treatment of diabetes.

Transcriptional profiling of ParA and ParB mutants in actively dividing cells of an opportunistic human pathogen Pseudomonas aeruginosa.

Accurate chromosome segregation to progeny cells is a fundamental process ensuring proper inheritance of genetic material. In bacteria with simple cell cycle, chromosome segregation follows replication initiation since duplicated oriC domains start segregating to opposite halves of the cell soon after they are made. ParA and ParB proteins together with specific DNA sequences are parts of the segregation machinery. ParA and ParB proteins in Pseudomonas aeruginosa are important for optimal growth, nucleoid segregation, cell division and motility. Comparative transcriptome analysis of parA null and parB null mutants versus parental P. aeruginosa PAO1161 strain demonstrated global changes in gene expression pattern in logarithmically growing planktonic cultures. The set of genes similarly affected in both mutant strains is designated Par regulon and comprises 536 genes. The Par regulon includes genes controlled by two sigma factors (RpoN and PvdS) as well as known and putative transcriptional regulators. In the absence of Par proteins, a large number of genes from RpoS regulon is induced, reflecting the need for slowing down the cell growth rate and decelerating the metabolic processes. Changes in the expression profiles of genes involved in c-di-GMP turnover point out the role of this effector in such signal transmission. Microarray data for chosen genes were confirmed by RT-qPCR analysis. The promoter regions of selected genes were cloned upstream of the promoter-less lacZ gene and analyzed in the heterologous host E. coliΔlac. Regulation by ParA and ParB of P. aeruginosa was confirmed for some of the tested promoters. Our data demonstrate that ParA and ParB besides their role in accurate chromosome segregation may act as modulators of genes expression. Directly or indirectly, Par proteins are part of the wider regulatory network in P. aeruginosa linking the process of chromosome segregation with the cell growth, division and motility

Application and verification of a water balance model with distributed parameters (on the example of Rega river basin)

The purpose of the study reported was to apply and verify a model of water balance of spatially distributed parameters in a meso-scale river catchment. The model was applied in the basin of Rega river, with the use of meteorological and hydrological measurement data from the years 1956 -1995. In modelling, due account was taken of the land use changes having occurred during the 40-year period considered. The output from modelling was constituted by the raster maps of area evaporation, surface runoff and supply of the underground water resources. On the basis of these results the magnitude of outflow and the structure of water balance were calculated for three river gauge profiles. The deviations of the model-based calculated outflow values from the measured ones were maximally equal +10% for the entire 40-year period and +20% in one of the 5-year sub-periods

Geographical dimension of internet domains

One of the two highest levels of Internet domains has its geographical dimension. It consists of the so-called country-code domains (ccTLDs) assigned to the individual countries of the world according to the standard ISO 3166. Some of these domains took over the role of worldwide functional domains and large income from their sale caused economic and social changes in the countries with attractive country-code domains

Genes from overrepresented regulons affected by mutations in <i>parA</i> and <i>parB</i> genes in <i>P. aeruginosa</i>.

<p><b>(A)</b> RpoS, QS, RpoN(KinB) and stress regulated genes with altered expression in <i>par</i> mutants presented as Venn diagram illustrating separate and common genes classified into presented regulons (according to <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0087276#pone.0087276.s001" target="_blank">Table S1</a>). (<b>B)</b> The most potent known regulators with changed expression in <i>par</i> mutants. The functions they influence are given.</p

Validation of microarray data by RT-qPCR analysis.

<p>The RT-qPCR on RNA samples applied for microarrays analysis for chosen genes with changed mRNA level in <i>P. aeruginosa par</i> mutants (p-value ≤0.05; fold change ≥2). Abbreviations: MC - microarray data; RT - RT-qPCR data; SD RT - standard deviation for RT-qPCR analysis; nd - change not detected. Standard deviation from at least three independent experiments is presented.</p

Number of genes with changed expression in <i>P. aeruginosa parA</i>_null and <i>parB</i>_null strains.

<p>The loci with altered expression in <i>parA</i>_null and <i>parB</i>_null as compared to reference PAO1161 <i>P. aeruginosa</i> (WT), indicated by pairwise comparison of microarray data (fold change FC ≥2; p-value ≤0.05). Number of genes (including intergenic regions and tRNA genes) with indicated mRNA level change are shown. Genes were grouped according to the magnitude of differential expression.</p

Functional classification of genes differentially expressed in logarithmically growing cultures of <i>P. aeruginosa par</i> mutants.

<p>(<b>A</b>) Venn diagram demonstrating the number of genes with changed mRNA level (fold change ≥2; p-value ≤0.05) in <i>parA</i>_null and <i>parB</i>_null mutant strains as compared to reference WT PAO1161 <i>P. aeruginosa</i> strain. Three gene set lists were created representing genes differentially expressed only in <i>parA</i>_null, with different expression in both <i>par</i> mutants (common in <i>parA</i>_null and <i>parB</i>_null) and with different mRNA level only in <i>parB</i>_null. (<b>B</b>) Functional classification of identified genes according to their predicted or known functions. Functional classes are taken from PseudoCAP <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0087276#pone.0087276-Winsor1" target="_blank">[29]</a> and are listed on the left with abbreviations in brackets. The original PseudoCAP functional categories were further grouped into six larger classes encompassing: (<b>I</b>) adaptation, protection, motility (green panel); (<b>II</b>) membrane proteins, transport, secretion (blue panel); (<b>III</b>) signal transduction, regulatory functions (red panel); (<b>IV</b>) cellular processes (yellow panel); (<b>V</b>) metabolism (orange panel); (<b>VI</b>) hypothetical, unknown functions (grey panel). (<b>C</b>) The pie charts created for each gene set list illustrating the percentage of genes in each class accounted for the total number of genes with changed expression for: only in <i>parA</i>_null, common in <i>parA</i>_null and <i>parB</i>_null and only in <i>parB</i>_null gene set list.</p

Gene expression analysis in logarithmically growing cultures of <i>parA</i>_null, <i>parB</i>_null strains versus WT <i>P. aeruginosa</i>.

<p>(<b>A</b>) Quality analysis of three biological replicates of studied strains <i>parA</i>_null, <i>parB</i>_null and WT of PAO1161 <i>P. aeruginosa</i> by principle component analysis (PCA) of data obtained from expression microarray analysis. The first principle component (PC#1) accounted for 68% and the second principle component PC#2 for 19.7% of the total variation in the dataset. The plot indicates that the transcriptome data are of high quality as the samples cluster together according to the strain: green - WT, red - <i>parA</i>_null, blue - <i>parB</i>_null. (<b>B</b>) and (<b>C</b>) Cluster analysis of the normalized gene expression for genes that were differentially regulated in <i>parA</i>_null and <i>parB</i>_null strains as compared to the WT, respectively.</p

Ashwagandha <i>(Withania somnifera)</i>—Current Research on the Health-Promoting Activities: A Narrative Review

In recent years, there has been a significant surge in reports on the health-promoting benefits of winter cherry (Withania somnifera), also known as Ashwagandha. Its current research covers many aspects of human health, including neuroprotective, sedative and adaptogenic effects and effects on sleep. There are also reports of anti-inflammatory, antimicrobial, cardioprotective and anti-diabetic properties. Furthermore, there are reports of reproductive outcomes and tarcicidal hormone action. This growing body of research on Ashwagandha highlights its potential as a valuable natural remedy for many health concerns. This narrative review delves into the most recent findings and provides a comprehensive overview of the current understanding of ashwagandha’s potential uses and any known safety concerns and contraindications