Saroglitazar is noninferior to fenofibrate in reducing triglyceride levels in hypertriglyceridemic patients in a randomized clinical trial

Saroglitazar, being a dual PPAR-α/γ agonist, has shown beneficial effect in diabetic dyslipidemia and hypertriglyceridemia. Fibrates are commonly used to treat severe hypertriglyceridemia. However, the effect of saroglitazar in patients with moderate to severe hypertriglyceridemia was not evaluated. We conducted a study to compare the efficacy and safety of saroglitazar (4 mg) with fenofibrate (160 mg) in patients with moderate to severe hypertriglyceridemia. This was a multicenter, randomized, double-blinded, double-dummy, active-control, and noninferiority trial in adult patients with fasting triglyceride (TG) levels of 500–1,500 mg/dl. The patients were randomized in a 1:1 ratio to receive daily dose of saroglitazar or fenofibrate for 12 weeks. The primary efficacy end point was the percent change in TG levels at week 12 relative to baseline. The study comprised of 41 patients in the saroglitazar group and 41 patients in the fenofibrate group. We found that the percent reduction from baseline in TG levels at week 12 was significantly higher in the saroglitazar group (least square mean = ?55.3%; SE = 4.9) compared with the fenofibrate group (least square mean = ?41.1%; SE = 4.9; P = 0.048). Overall, 37 treatment-emergent adverse events (AEs) were reported in 24 patients (saroglitazar: 13; fenofibrate: 11). No serious AEs were reported, and no patient discontinued the study because of AEs. We conclude that saroglitazar (4 mg) is noninferior to fenofibrate (160 mg) in reducing TG levels after 12 weeks of treatment, was safe, and well tolerated.     

Rice G protein γ subunit qPE9-1 modulates root elongation for phosphorus uptake by involving 14-3-3 protein OsGF14b and plasma membrane H+-ATPase

Heterotrimeric G protein is involved in plant growth and development, while the role of rice (Oryza sativa) G protein γ subunit qPE9-1 in response to low-phosphorus (LP) conditions remains unclear. The gene expression of qPE9-1 was significantly induced in rice roots under LP conditions. Rice varieties carrying the qPE9-1 allele showed a stronger primary root response to LP than the varieties carrying the qpe9-1 allele (mutant of the qPE9-1 allele). Transgenic rice plants with the qPE9-1 allele had longer primary roots and higher P concentrations than those with the qpe9-1 allele under LP conditions. The plasma membrane (PM) H⁺-ATPase was important for the qPE9-1-mediated response to LP. Furthermore, OsGF14b, a 14-3-3 protein that acts as a key component in activating PM H⁺-ATPase for root elongation, is also involved in the qPE9-1 mediation. Moreover, the overexpression of OsGF14b in WYJ8 (carrying the qpe9-1 allele) partially increased primary root length under LP conditions. Experiments using R18 peptide (a 14-3-3 protein inhibitor) showed that qPE9-1 is important for primary root elongation and H⁺ efflux under LP conditions by involving the 14-3-3 protein. In addition, rhizosheath weight, total P content, and the rhizosheath soil Olsen-P concentration of qPE9-1 lines were higher than those of qpe9-1 lines under soil drying and LP conditions. These results suggest that the G protein γ subunit qPE9-1 in rice plants modulates root elongation for phosphorus uptake by involving the 14-3-3 protein OsGF14b and PM H⁺-ATPase, which is required for rice P use.     

Variation of Essential Oil Content and Composition,Phenolics, and Yield Related Traits Using Different Pollination Systems in Populations of Thymus Species

The production of self-pollinated plants could be important for improving medicinal plants secondary metabolites. In this study, 11 Thymus populations from eight species were evaluated to determine the effect of self and open pollination on agro-morphological characteristics, total phenolic content (TPC), essential oil (EO) content, and EO components. Inbreeding led to some positive effects of above mentioned traits in most of the studied populations. Total phenolic content ranged from 7.07 to 52.69 mg tannic acid equivalents (TAE) g⁻¹ dry weight (DW) in open pollinated derived populations, while it varied from 1.2 to 55.03 mg TAE g⁻¹ DW in self-pollinated ones. Under open and self-pollination condition, the highest EO content was obtained in T. trautvetteri (3.37 %) and T. pubescens (1.96 %), respectively. Gas chromatography-mass spectrometry (GC/MS) identified 42 compounds including thymol, carvacrol, linalool, p-cymene, γ-terpinene, terpinen-4-ol, and α-terpineol as the main compounds. In most cases, selfed plants compared to open pollinated ones, revealed higher thymol content. T. daenensis-1 showed a significant increase in thymol content (from 25.22 % to 74.3 %) due to self-pollination. Moreover, self-pollination led to emergence of some new compounds. Carvacrol methyl ether was the constituents of Thymus EO that are being reported in self-pollinated populations. Finally, inbreeding in Thymus might be suggested as a useful tool to increase genetic homogeneity for the selection of superior plants for improving secondary metabolite.     

LncRNA TP73-AS1 enhances the malignant properties of pancreatic ductal adenocarcinoma by increasing MMP14 expression through miRNA -200a sponging

Pancreatic ductal adenocarcinoma (PDAC) is an invasive and aggressive cancer that remains a major threat to human health across the globe. Despite advances in cancer treatments and diagnosis, the prognosis of PDAC patients remains poor. New and more effective PDAC therapies are therefore urgently required. In this study, we identified a novel host factor, namely the LncRNA TP73-AS1, as overexpressed in PDAC tissues compared to adjacent healthy tissue samples. The overexpression of TP-73-AS1 was found to correlate with both PDAC stage and lymph node metastasis. To reveal its role in PDCA, we targeted TP73-AS1 using LnRNA inhibitors in a range of pancreatic cancer (PC) cell lines. We found that the inhibition of TP73-AS1 led to a loss of MMP14 expression in PC cells and significantly inhibited their migratory and invasive capacity. No effects of TP73-AS1 on cell survival or proliferation were observed. Mechanistically, we found that TP73-AS1 suppressed the expression of the known oncogenic miR-200a. Taken together, these data highlight the prognostic potential of TP73-AS1 for PC patients and highlight it as a potential anti-PDAC therapeutic target.     

Transport of groundwater-borne phosphorus to Lake Bysjön,South Sweden

Lake Bysjön is a hypertrophic seepage lake, with groundwater as a main external source of phosphorus. Twelve groundwater samples from the vicinity of the lake were high in phosphate (0.4 to 11 mg l^–1, mean value 2.57 mg l^–1 PO₄-P), both within the riparian zone and in two shallow wells located upstreams the lake in the nearby village. Phosphorus sorption capacity of four sand samples measured with the Langmuir isotherm method was low (7.3 to 121,1 mg kg^–1 PO₄-P), with the lowest values found within the riparian zone. It is suggested that the phosphorus originates from garden fertilizers and other human sources, and that the low absorption capacity of the soils is caused by the leaching of calcium from the watershed, a process which started some 3000 years ago. Riparian zone itself has almost no retention capacity, and processes within it (e.g., redox-related) have only secondary importance for the transport of phosphorus to the lake.     

A review of phosphorus efficiency in wheat

More efficient utilization of phosphorus by wheat plants is needed to extend the useful life of the phosphate reserves in the world, to reduce the cost of producing crops, and to improve the value of the grain and the straw produced. In this paper definitions of efficient use of phosphorus by wheat are reviewed, genotypic variation in phosphorus efficiency is reported, some consequences of breeding for greater efficiency are discussed, and ways to select more efficient genotypes are suggested.