THDP17 Decreases Ammonia Production through Glutaminase Inhibition. A New Drug for Hepatic Encephalopathy Therapy

Ammonia production is implicated in the pathogenesis of hepatic encephalopathy (HE), being intestinal glutaminase activity the main source for ammonia. Management of ammonia formation can be effective in HE treatment by lowering intestinal ammonia production. The use of glutaminase inhibitors represents one way to achieve this goal. In this work, we have performed a search for specific inhibitors that could decrease glutaminase activity by screening two different groups of compounds: i) a group integrated by a diverse, highly pure small molecule compounds derived from thiourea ranging from 200 to 800 Daltons; and ii) a group integrated by commonly use compounds in the treatment of HE. Results shown that THDP-17 (10 µM), a thiourea derivate product, could inhibit the intestinal glutaminase activity (57.4±6.7%). Inhibitory effect was tissue dependent, ranging from 40±5.5% to 80±7.8% in an uncompetitive manner, showing V_max and K_m values of 384.62 µmol min⁻¹, 13.62 mM with THDP-17 10 µM, respectively. This compound also decreased the glutaminase activity in Caco-2 cell cultures, showing a reduction of ammonia and glutamate production, compared to control cultures. Therefore, the THDP-17 compound could be a good candidate for HE management, by lowering ammonia production.     

NLRP3 inflammasome suppression improves longevity and prevents cardiac aging in male mice

While NLRP3‐inflammasome has been implicated in cardiovascular diseases, its role in physiological cardiac aging is largely unknown. During aging, many alterations occur in the organism, which are associated with progressive impairment of metabolic pathways related to insulin resistance, autophagy dysfunction, and inflammation. Here, we investigated the molecular mechanisms through which NLRP3 inhibition may attenuate cardiac aging. Ablation of NLRP3‐inflammasome protected mice from age‐related increased insulin sensitivity, reduced IGF‐1 and leptin/adiponectin ratio levels, and reduced cardiac damage with protection of the prolongation of the age‐dependent PR interval, which is associated with atrial fibrillation by cardiovascular aging and reduced telomere shortening. Furthermore, old NLRP3 KO mice showed an inhibition of the PI3K/AKT/mTOR pathway and autophagy improvement, compared with old wild mice and preserved Nampt‐mediated NAD⁺ levels with increased SIRT1 protein expression. These findings suggest that suppression of NLRP3 prevented many age‐associated changes in the heart, preserved cardiac function of aged mice and increased lifespan.     

Plant ontogenetic changes in vein and stomatal traits and their relationship with economic traits in leaves of three Mediterranean oaks

3种地中海橡树在叶脉和气孔性状上的个体发育性变化及其与叶片经济性状的关系 我们比较了3个地中海栎属(Quercus)树种幼苗和成龄树的叶脉和气孔性状。之前的研究表明,幼苗的气体交换率往往比成龄树的要高。我们的研究目标是确认叶脉和气孔的性状在整个植物个体发育过程中是否会随着气体交换率的变化而同步改变。我们提出了以下两个备选假设：幼苗比成龄树有着更高的叶脉和气孔密度(假设1);幼苗在维管组织上的投资更少,从而降低了建设成本(假设2)。本研究是在西班牙中西部进行的,我们对每个树种不同生长阶段的植株随机采集了10个样本。我们测量了气孔和叶脉的平均性状(单位叶面积里的气孔大小和数量、叶脉密度、叶脉体积、叶脉到表皮的距离),比叶质量和叶片厚度。研究结果表明,细脉密度和单位面积叶脉体积随着树龄的增加而增加,这似乎与气体交换率方面的个体发育趋势不一致。这种差异支持了我们的假设2,说明植株在幼苗阶段减少对维管组织的投资以最大限度地提高生长速度是其当务之急。幼苗叶片中较大的叶脉间距可以由叶脉到表皮的较短距离所补偿。因此,薄叶片可能是幼苗的一个必要性状,它可以让水分沿较短路径输送到蒸发点,而无需对高成本的维管组织进行大量投资。     

Effect of mesenchymal stromal cells encapsulated within polyethylene glycol-collagen hydrogels formed in situ on alkali-burned corneas in an ex vivo organ culture model

Background aimsCorneal inflammation after alkali burns often results in vision loss due to corneal opacification and neovascularization. Mesenchymal stem cells (MSCs) and their secreted factors (secretome) have been studied for their anti-inflammatory and anti-angiogenic properties with encouraging results. However, topical instillation of MSCs or their secretome is often accompanied by issues related to delivery or rapid washout. Polyethylene glycol (PEG) and collagen are well-known biomaterials used extensively in scaffolds for tissue engineering. To effectively suppress alkaline burn-induced corneal injury, the authors proposed encapsulating MSCs within collagen gels cross-linked with multi-functional PEG-succinimidyl esters as a means to deliver the secretome of immobilized MSCs.MethodsHuman MSCs were added to a neutralized collagen solution and mixed with a solution of four-arm PEG-N-hydroxysuccinimide. An ex vivo organ culture was conducted using rabbit corneas injured by alkali burn. MSCs were encapsulated within PEG-collagen hydrogels and injected onto the wounded cornea immediately following alkali burn and washing. Photographs of the ocular surface were taken over a period of 7 days after the alkali burn and processed for immunohistochemical evaluation. Samples were split into three groups: injury without treatment, MSCs alone, and MSCs encapsulated within PEG-collagen hydrogels.ResultsAll corneas in ex vivo organ culture lost their transparency immediately after alkali burn, and only the groups treated with MSCs and MSCs encapsulated within PEG-collagen hydrogels recovered some transparency after 7 days. Immunohistochemical analysis revealed increased expression of vimentin in the anterior corneal stroma of the group without treatment indicative of fibrotic healing, whereas less stromal vimentin was detected in the group containing MSCs encapsulated within the PEG-collagen hydrogels.ConclusionsPEG-collagen hydrogels enable the encapsulation of viable MSCs capable of releasing secreted factors onto the ocular surface. Encapsulating MSCs within PEG-collagen hydrogels may be a promising method for delivering their therapeutic benefits in cases of ocular inflammatory diseases, such as alkali burn injuries.     

Biogeographical and bioclimatic outline of Antarctica

Abstract

This study proposes a bioclimatic characterization and a new biogeographic division for the Antarctic territories up to the province level following the criteria and models of Rivas-Martínez et al. The Antarctic Kingdom comprises the continent of Antarctica, the surrounding ice-covered Antarctic islands, and the associated cold oceanic islands and archipelagos. It has two biogeographic regions: the Antarctic Region and the Subantarctic Insular Region. The Antarctic Region includes the entire pergelid Antarctic continent and the surrounding islands and archipelagos, and is characterized by upper suprapolar hyperoceanic and oceanic or Polar pergelid bioclimates on the coasts. The region has been divided into three pr6ovinces: Maritime Antarctica, West Antarctica and East Antarctica. The Subantarctic Insular Region comprises the circumantarctic islands and archipelagos that are widespread at the southern tip of the planet’s most important oceans, mostly in the subtemperate latitudinal zone inside or not far from the Antarctic Convergence. Bioclimatically, all insular subantarctic territories (excluding the South-American Tierra de Fuego, Terra Magellanica and large islands) are characterized by thermo-suprapolar and semipolar antarctic hyperoceanic bioclimates on the coasts. Four provinces – Falklandian-South Georgian, Kerguelenian, Macquarian and Aucklandian-Campbellian – have been recognized in this region. All these units are characterized by floristic bioindicators.     

Uncovering the different scales in deer–forest interactions

Deer are regarded to be a keystone species as they play a crucial role in the way an ecosystem functions. Most deer–forest interaction studies apply a single scale — process of analyzing ecological interactions by only taking into account one dependent variable — to understand how deer browsing behavior shapes different forest components, but they overlook the fact that forests respond to multiple scales simultaneously. This research evaluates the effect of browsing by wild deer on temperate and boreal forests at different scales by synthesizing seminal papers, specifically (a) what are the effects of deer population density in forest regeneration? (b) What are the effects of deer when forests present diverging spatial characteristics? (c) What are the effects on vegetation at different temporal scales? and (d) What are the hierarchical effects of deer when considering other trophic levels? Additionally, a framework based on modern technology is proposed to answer the multiscale research questions previously identified. When analyzing deer–forest interactions at different scales, the strongest relationships occur at the extremes. For example: when deer assemblage occurs in low or high density and is composed of a mix of small and large species. As forests on poor soils remain restrained in size, isolated and chronically browsed. When forests harbor incomplete trophic levels, the effects spill over to lower trophic levels. To better understand the complexities in deer–forest interactions, researchers should combine technology‐based instruments like fixed sensors and drones with field‐tested methods such observational studies and experiments to tackle multiscale research questions.