Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) are incretin-derived glucose-lowering agents that have been used for the treatment of type 2 diabetes since 2007. Agents such as exenatide (short-acting and once weekly preparations), liraglutide, taspoglutide, albiglutide and lixisenatide lower fasting glucose and HbA 1c upon subcutaneous injection, leading to glycaemic control that is equivalent to, or better than, that observed with other oral glucose-lowering agents or bedtime insulin. However, varying proportions of patients report nausea and vomiting, adverse events that typically narrow the therapeutic dose range. Furthermore, GLP-1 RAs reduce fasting glucose to a clinically meaningful extent, but not into the normal range. GLP-1: a parent compound for novel incretin-based glucose-lowering drugsGlucagon-like peptide-1 (GLP-1) has attracted attention because of its ability to stimulate insulin secretion in a glucose-dependent manner, to suppress glucagon release when glucose concentrations are not in the hypoglycaemic range, and to elicit a number of extra-pancreatic effects (on appetite/satiety, gastrointestinal motility and the cardiovascular system) [1]. This spectrum of biological activities addresses important deficits typical for patients with type 2 diabetes (impaired beta cell function, hyperglucagonaemia, overeating/obesity, excessive postprandial rises in glucoseElectronic supplementary material The online version of this article (doi:10.1007/s00125-013-2953-6) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

Vildagliptin and sitagliptin affected incretin hormones, glucose concentrations, insulin and glucagon secretion in a similar manner. Inter-individual variations in L-cell feedback inhibition may indicate heterogeneity in the clinical response to DPP-4 inhibition.

Sitagliptin, in patients already treated with a GLP-1 receptor agonist (liraglutide), increased intact GLP-1 and GIP concentrations, but with marginal, non-significant effects on glycaemic control. GLP-1 receptors have probably been maximally stimulated by liraglutide. Our findings do not support combination treatment with GLP-1 receptor agonists and DPP-4 inhibitors, but longer-term trials are needed to support clinical recommendations.

Abiotic stress significantly limits plant growth and production. Drought, in particular, is a severe constraint that affects growth and limits agricultural productivity on a global scale. Water stress induces in plants a set of morpho-anatomical (modification of root and leaf structure), physiological, and biochemical (relative water content, membrane stability, photosynthesis, hormonal balance, antioxidant systems, and osmolyte accumulation) changes mainly employed to cope with the drought stress. These strategies allow the plant to overcome the unfavorable period of limited water availability. Currently, a promising alternative is available to improve plant growth and tolerance under drought conditions. The use of osmotolerant plant growth-promoting rhizobacteria (PGPR) as inoculants can alleviate water stress by increasing the water use efficiency of the plant. The PGPR improve the tolerance of plants to drought, through changes in the morphology and architecture of the root system, production of phytohormones, extracellular polysaccharides, ACC 1-(aminocyclopropane-1-carboxylate) deaminase, volatile chemicals, and osmolyte accumulation. They may also enhance the antioxidant defense system and induce transcriptional regulation of stress response genes. This review addresses the effects of stress on plant growth, adaptation, and response to drought conditions and discusses the significant potential of PGPR to modulate the physiological response against water scarcity, ensuring plant survival and improving the resistance and growth of agricultural crops.

Salinity stress is among the key challenges for sustainable food production. It is continuously increasing against the backdrop of constant climate change and anthropogenic practices leading to a huge drop in soil, water, and cultivated crop quality and productivity. Halotolerant plants represent hot spots for endophytic bacteria which may have mechanisms to overcome salt stress. This research initiative aims to highlight the possible exploitation of bacterial endophytes as a microbial biotechnology tool in the productive success of plants exposed to saline stress. We started by solely studying the mechanisms of stress tolerance by plants and halotolerant bacteria. After that, we focused on the beneficial mechanisms of endophytic bacteria in salt stress mitigation. On one side, potent bacterium works by promoting plant performances by facilitating the plant’s nutrient uptake (P, K, Zn, N, and Fe) and by promoting the production of growth hormones (IAA and CKs). On the other side, they balance stress phytohormones (ABA, JA, GA, and ACC) produced by plants in case of soil salt augmentation. The selected potent endophytic bacteria could be exploited and applied to ameliorate the production and salt tolerance of food crops. Lastly, we elucidated deeper advanced technologies including (i) genomics unveiling the plant’s culture-dependent and culture-independent microbiomes, (ii) metabolomics focusing on genes’ metabolic pathways to discover novel secondary metabolites, (iii) transcriptomics studying gene expression, and (iv) proteomics delimiting proteins expressed in stress alleviation. These technologies have been used to understand the plant–bacterial mechanisms of interaction to combat salt stress.

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The growing importance of forest plantations increases the demand for phytopathogen resistant forest trees. This study describes an effective method for early detection and identification of the main fungal phytopathogens in planting material of silver birch (Betula pendula) and downy birch (B. pubescens), based on the estimation of the size of the internal transcribed spacers (ITS1 and ITS2) in the 18S-5.8S-28S rDNA gene cluster, which are species-specific for most micromycetes. The electrophoretic assay of the ITS1 and ITS2 loci has allowed us to identify predominant phytopathogenic fungal species in downy and silver birch in planta. This new molecular genetic method can be used to screen birch and other forest trees for different fungal pathogens to evaluate disease resistance. This information can be useful in breeding new genotypes of forest trees, including transgenic clones with modified wood composition.

Частота бактериальных коинфекций среди пациентов с COVID-19 невелика, поэтому избыточное назначение антибиотиков может способствовать селекции резистентных штаммов энтеробактерий и грамотрицательных неферментирующих бактерий.Цель исследования -оценка локальных особенностей и генетических механизмов антибиотикорезистентности K. pneumoniae на фоне пандемии инфекции COVID-19.Материал и методы. Отобрано 37 устойчивых к карбапенемам штаммов K. pneumoniae, выделенных в 2016, 2017 и 2020 гг. от госпитализированных пациентов, в том числе 15 штаммов, выделенных от пациентов с COVID-19. Методом микроразведений в бульоне определены минимальные подавляющие концентрации (МПК) меропенема и колистина. Определение МПК эравациклина, цефидерокола, цефтазидима/авибактама, меропенема/ваборбактама, имипенема/релебактама выполнено с использованием диагностической системы Sensititre на планшетах EUMDROXF. Чувствительность к 11 комбинациям из 2 разных антибиотиков определена модифицированным методом тестирования бактерицидности различных комбинаций. Для 4 штаммов K. pneumoniae выполнено высокопроизводительное секвенирование с последующим поиском детерминант антибиотикорезистентности и вирулентности, а также с оценкой плазмидных профилей.Результаты. Все штаммы были устойчивы к меропенему (МПК 50 32 мг/л, МПК 90 128 мг/л) и продуцировали карбапенемазы KPC и OXA-48. Штаммы, выделенные в 2016-2017 гг., были чувствительны к колистину (МПК 2 мг/л), в 2020 г. сохраняли чувствительность только 26,7% штаммов (МПК 50 64 мг/л, МПК 90 256 мг/л). Чувствительность к комбинациям из 2 антибиотиков с включением колистина сократилась с 84,6-100% в 2016-2017 гг. до 26,7-66,7% в 2020 г. Выделенные в 2020 г. штаммы сохраняли чувствительность к цефтазидиму/авибактаму (МПК 1 мг/л). Выявлено 5 штаммов, устойчивых к цефидероколу c МПК 8 мг/л. Штаммы 2564 и 3125, выделенные в 2020 г. из мокроты пациентов с инфекцией COVID-19, относились к различным сиквенс-типам (ST512 и ST23) и содержали ген карбапенемазы bla OXA-48, штамм 2564 дополнительно содержал ген карбапенемазы bla KPC-27. Устойчивость к колистину была вызвана инактивацией генов mgrB за счет инсерций IS1-и IS5-подобных транспозонов.Заключение. Выполненные генетические исследования демонстрируют многообразие механизмов антибиотикорезистентности у K. pneumoniae, приводящих к формированию устойчивости в том числе к антибиотикам, до настоящего времени не использовавшимся в Республике Беларусь.