Changes of plasma fibroblast growth factor-21 (FGF-21) in oral glucose tolerance test and effects of metformin on FGF-21 levels in type 2 diabetes mellitus

Wstęp: Badanie przeprowadzono w celu ustalenia, czy czynnik wzrostu fibroblastów-21 (FGF-21) uczestniczy w regulacji stężenia glukozy i czy zastosowanie metforminy u chorych na cukrzycę wpływa na stężenie FGF-21. Materiał i metody: Do badania włączono 43 osoby, w tym 27 chorych z nowo rozpoznaną cukrzycą typu 2 (nT2DM). U wszystkich przeprowadzono test doustnego obciążenia 75 g glukozy (OGTT). Próbki krwi pobrano w 0., 60.,120. i 180. minucie testu. Osobom z nT2DM zaproponowano udział w dalszych badaniach; zastosowano u nich metforminę w dawce 1,0 g/dobę przez tydzień. Wyniki: Zmiany stężenia FGF-21 w osoczu podczas OGTT zaobserwowano tylko w grupie chorych na nT2DM; w grupie kontrolnej stężenie FGF-21 pozostało niezmienione. Nie stwierdzono, by stężenia FGF-21 w poszczególnych punktach czasowych różniły się w zależności od płci badanych (p < 0,05). Zastosowanie metforminy u osób z nT2DM spowodowało istotne zmniejszenie stężeń glukozy i FGF-21 we wszystkich punktach czasowych OGTT oraz zmniejszenie stężenia insuliny w 60. i 180. minucie, co wskazuje na obniżenie wskaźnika HOMA-IR. Wnioski: FGF-21 nie uczestniczy w krótkoterminowej regulacji glikemii u ludzi, a zmiany jego stężenia podczas OGTT są opóźnione w T2DM. Być może FGF-21 bierze udział w metabolizowaniu metforminy, zwiększając wrażliwość na glukozę i insulinę. (Endokrynol Pol 2013; 64 (3): 220&#8211;224)Introduction: The objectives of our study were to investigate whether fibroblast growth factor-21 (FGF-21) is involved in short-term regulation of glucose and the change of FGF-21 after metformin use in diabetic subjects. Material and methods: 43 subjects were recruited in the study, including 27 new-onset type 2 diabetes patients (nT2DM). A 75 g oral glucose tolerance test (OGTT) was administered to them. Blood samples were taken at 0, 60 ,120 and 180 minute of OGTT. nT2DM subjects were invited for further investigation, metformin was administered in a dose of 1.0 g every day for 1 week. Results: Plasma FGF-21 changed significantly in the nT2DM group during the OGTT administration but not in the control group. No gender differences were observed at different time points in FGF-21 levels (p < 0.05). Administration of metformin for nT2DM resulted in a significant decrease in both glucose and FGF-21 at all OGTT times and in insulin at 60 min and 180 min, indicative of a decrease in HOMA-IR. Conclusion: FGF-21 does not seem to be involved in short-term regulation of glycaemia in human subjects, and the change in OGTT delayed in T2DM. FGF-21 may participate in the processing of metformin, improving glucose and insulin sensitivity. (Pol J Endocrinol 2013; 64 (3): 220&#8211;224

In vitro and in vivo release studies of fluorouracil acetic acid-dextran conjugates

Fluorouracil acetic acid–dextran (FUD) conjugates were synthesized and its stability in buffer solution has been investigated previously in our laboratory. In this contribution, the in vitro and in vivo releases of FUD were investigated. The results revealed that no detectable 5-fluorouracil (5-FU, FU) found during in vitro and in vivo release studies. The in vitro release was dependent on both degree of substitution (DS) of 5-fluorouracil-1-acetic acid (5-FUA) in FUD and gastrointestinal tract section (GITs). 5- FUA can be completely released from the conjugates with DS of 10.3 % (wt/wt) in homogenates of cecum and colon content. After oral administration in rats, FUD with DS of 10.3 % showed colon specific delivery of 5-FUA compared with that of free 5-FUA. The target index (TI) of the conjugate was 1.93 in cecum contents and 2.09 in colon contents respectively within 24 h. The results indicated that the conjugates can be used as colon-specific delivery system of 5-FUA.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Novel multi-biotin grafted poly(lactic acid) and its self-assembling nanoparticles capable of binding to streptavidin

Targeted drug delivery requires novel biodegradable, specific binding systems with longer circulation time. The aim of this study was to prepare biotinylated poly(lactic acid) (PLA) nanoparticles (NPs) which can meet regular requirements as well conjugate more biotins in the polymer to provide better binding with streptavidin. A biotin-graft-PLA was synthesized based on previously published biodegradable poly(ethylene glycol) (PEG)-graft-PLA, with one polymer molecule containing three PEG molecules. Newly synthesized biotin-graft-PLA had three biotins per polymer molecule, higher than the previous biotinylated PLA (≤1 biotin per polymer molecule). A PEG with a much lower molecular weight (MW ~1900) than the previous biotinylated PLA (PEG MW ≥ 3800), and thus more biocompatible, was used which supplied good nonspecific protein-resistant property compatible to PEG-graft-PLA, suggesting its possible longer stay in the bloodstream. Biotin-graft-PLA specifically bound to streptavidin and self-assembled into NPs, during which naproxen, a model small molecule (MW 230 Da) and hydrophobic drug, was encapsulated (encapsulation efficiency 51.88%). The naproxen-loaded NPs with particle size and zeta potential of 175 nm and −27.35 mV realized controlled release within 170 hours, comparable to previous studies. The biotin-graft-PLA NPs adhered approximately two-fold more on streptavidin film and on biotin film via a streptavidin arm both in static and dynamic conditions compared with PEG-graft-PLA NPs, the proven nonspecific protein-resistant NPs. The specific binding of biotin-graft-PLA NPs with streptavidin and with biotin using streptavidin arm, as well as its entrapment and controlled release for naproxen, suggest potential applications in targeted drug delivery

Belowground rhizomes in paleosols:The hidden half of an Early Devonian vascular plant

The colonization of terrestrial environments by rooted vascular plants had far-reaching impacts on the Earth system. However, the belowground structures of early vascular plants are rarely documented, and thus the plant-soil interactions in early terrestrial ecosystems are poorly understood. Here we report the earliest rooted paleosols (fossil soils) in Asia from Early Devonian deposits of Yunnan, China. Plant traces are extensive within the soil and occur as complex network-like structures, which are interpreted as representing long-lived, belowground rhizomes of the basal lycopsid Drepanophycus. The rhizomes produced large clones and helped the plant survive frequent sediment burial in well-drained soils within a seasonal wet-dry climate zone. Rhizome networks contributed to the accumulation and pedogenesis of floodplain sediments and increased the soil stabilizing effects of early plants. Predating the appearance of trees with deep roots in the Middle Devonian, plant rhizomes have long functioned in the belowground soil ecosystem. This study presents strong, direct evidence for plant-soil interactions at an early stage of vascular plant radiation. Soil stabilization by complex rhizome systems was apparently widespread, and contributed to landscape modification at an earlier time than had been appreciated.National Natural Science Foundation of China [41272018]; Yunnan Key Laboratory for Palaeobiology, Yunnan University [2015DG007-KF04]; Key Laboratory of Economic Stratigraphy and Palaeogeography, Chinese Academy of Sciences (Nanjing Institute of Geology and Palaeontology)SCI(E)[email protected]

CXCL9 Is a Potential Biomarker of Immune Infiltration Associated With Favorable Prognosis in ER-Negative Breast Cancer

The chemokine CXCL9 (C-X-C motif chemokine ligand 9) has been reported to be required for antitumour immune responses following immune checkpoint blockade. In this study, we sought to investigate the potential value of CXCL9 according to immune responses in patients with breast cancer (BC). A variety of open-source databases and online tools were used to explore the expression features and prognostic significance of CXCL9 in BC and its correlation with immune-related biomarkers followed by subsequent verification with immunohistochemistry experiments. The CXCL9 mRNA level was found to be significantly higher in BC than in normal tissue and was associated with better survival outcomes in patients with ER-negative tumours. Moreover, CXCL9 is significantly correlated with immune cell infiltration and immune-related biomarkers, including CTLA4, GZMB, LAG3, PDCD1 and HAVCR2. Finally, we performed immunohistochemistry with breast cancer tissue samples and observed that CXCL9 is highly expressed in the ER-negative subgroup and positively correlated with the immune-related factors LAG3, PD1, PDL1 and CTLA4 to varying degrees. These findings suggest that CXCL9 is an underlying biomarker for predicting the status of immune infiltration in ER-negative breast cancer

Genome-wide analysis and characterization of Dendrocalamus farinosus SUT gene family reveal DfSUT4 involvement in sucrose transportation in plants

Sucrose is the main transported form of photosynthetic products. Sucrose transporter (SUT) participates in the translocation of sucrose from source to sink, which is important for the growth and development of plants. Dendrocalamus farinosus is an important economic crop in southwestern China because of its high growth rate, high fiber content, and dual usage for food and timber, but the mechanism of sucrose transportation in D. farinosus is unclear. In this study, a total of 12 SUT transporter genes were determined in D. farinosus by whole-genome identification. DfSUT2, DfSUT7, and DfSUT11 were homologs of rice OsSUT2, while DfSUT4 was a homolog of OsSUT4, and these four DfSUT genes were expressed in the leaf, internode, node, and bamboo shoots of D. farinosus. In addition, DfSUT family genes were involved in photosynthetic product distribution, ABA/MeJA responses, and drought resistance, especially DfSUT4. The function of DfSUT4 was then verified in Nicotiana tabacum. DfSUT4 was localized mainly in the leaf mesophyll and stem phloem of pDfSUT4::GUS transgenic plant. The overexpression of DfSUT4 gene in transgenic plant showed increases of photosynthetic rate, above-ground biomass, thousand grain weight, and cellulose content. Our findings altogether indicate that DfSUT4 can be a candidate gene that can be involved in phloem sucrose transportation from the source leaves to the sink organs, phytohormone responses, abiotic stress, and fiber formation in plants, which is very important in the genetic improvement of D. farinosus and other crops

Phenotypic Differentiation Is Associated with Gender Plasticity and Its Responsive Delay to Environmental Changes in Alternanthera philoxeroides – Phenotypic Differentiation in Alligator Weed

Phenotypic plasticity is common in many taxa, and it may increase an organism's fitness in heterogeneous environments. However, in some cases, the frequency of environmental changes can be faster than the ability of the individual to produce new adaptive phenotypes. The importance of such a time delay in terms of individual fitness and species adaptability has not been well studied. Here, we studied gender plasticity of Alternanthera philoxeroides to address this issue through a reciprocal transplant experiment. We observed that the genders of A. philoxeroides were plastic and reversible between monoclinous and pistillody depending on habitats, the offspring maintained the maternal genders in the first year but changed from year 2 to 5, and there was a cubic relationship between the rate of population gender changes and environmental variations. This relationship indicates that the species must overcome a threshold of environmental variations to switch its developmental path ways between the two genders. This threshold and the maternal gender stability cause a significant delay of gender changes in new environments. At the same time, they result in and maintain the two distinct habitat dependent gender phenotypes. We also observed that there was a significant and adaptive life-history differentiation between monoclinous and pistillody individuals and the gender phenotypes were developmentally linked with the life-history traits. Therefore, the gender phenotypes are adaptive. Low seed production, seed germination failure and matching phenotypes to habitats by gender plasticity indicate that the adaptive phenotypic diversity in A. philoxeroides may not be the result of ecological selection, but of gender plasticity. The delay of the adaptive gender phenotype realization in changing environments can maintain the differentiation between gender systems and their associated life-history traits, which may be an important component in evolution of novel traits and taxonomic diversity

Transcription and splicing regulation in human umbilical vein endothelial cells under hypoxic stress conditions by exon array

<p>Abstract</p> <p>Background</p> <p>The balance between endothelial cell survival and apoptosis during stress is an important cellular process for vessel integrity and vascular homeostasis, and it is also pivotal in angiogenesis during the development of many vascular diseases. However, the underlying molecular mechanisms remain largely unknown. Although both transcription and alternative splicing are important in regulating gene expression in endothelial cells under stress, the regulatory mechanisms underlying this state and their interactions have not yet been studied on a genome-wide basis.</p> <p>Results</p> <p>Human umbilical vein endothelial cells (HUVECs) were treated with cobalt chloride (CoCl₂) both to mimic hypoxia and to induce cell apoptosis and alternative splicing responses. Cell apoptosis rate analysis indicated that HUVECs exposed to 300 μM CoCl₂for 24 hrs were initially counterbalancing apoptosis with cell survival. We therefore used the Affymetrix exon array system to determine genome-wide transcript- and exon-level differential expression. Other than 1583 differentially expressed transcripts, 342 alternatively spliced exons were detected and classified by different splicing types. Sixteen alternatively spliced exons were validated by RT-PCR. Furthermore, direct evidence for the ongoing balance between HUVEC survival and apoptosis was provided by Gene Ontology (GO) and protein function, as well as protein domain and pathway enrichment analyses of the differentially expressed transcripts. Importantly, a novel molecular module, in which the heat shock protein (HSP) families play a significant role, was found to be activated under mimicked hypoxia conditions. In addition, 46% of the transcripts containing stress-modulated exons were differentially expressed, indicating the possibility of combinatorial regulation of transcription and splicing.</p> <p>Conclusion</p> <p>The exon array system effectively profiles gene expression and splicing on the genome-wide scale. Based on this approach, our data suggest that transcription and splicing not only regulate gene expression, but also carry out combinational regulation of the balance between survival and apoptosis of HUVECs under mimicked hypoxia conditions. Since cell survival following the apoptotic challenge is pivotal in angiogenesis during the development of many vascular diseases, our results may advance the knowledge of multilevel gene regulation in endothelial cells under physiological and pathological conditions.</p

Disentangling the effects of vapor pressure deficit on northern terrestrial vegetation productivity

The impact of atmospheric vapor pressure deficit (VPD) on plant photosynthesis has long been acknowledged, but large interactions with air temperature (T) and soil moisture (SM) still hinder a complete understanding of the influence of VPD on vegetation production across various climate zones. Here, we found a diverging response of productivity to VPD in the Northern Hemisphere by excluding interactive effects of VPD with T and SM. The interactions between VPD and T/SM not only offset the potential positive impact of warming on vegetation productivity but also amplifies the negative effect of soil drying. Notably, for high-latitude ecosystems, there occurs a pronounced shift in vegetation productivity\u27s response to VPD during the growing season when VPD surpasses a threshold of 3.5 to 4.0 hectopascals. These results yield previously unknown insights into the role of VPD in terrestrial ecosystems and enhance our comprehension of the terrestrial carbon cycle\u27s response to global warming