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[en] Highlights: • RhoA expression and its activity were decreased in HG-injured podocytes in vitro and in vivo. • Loss of RhoA by siRNA resulted in podocyte apoptosis and proteinuria. • RhoA deficiency could reduce the nuclear protein expression of YAP in vitro and in vivo. • Podocyte apoptosis induced by RhoA knockdown was significantly abolished by over expressing active YAP. • RhoA played a critical role in DN probably by mediating the podocyte apoptosis through YAP. RhoA may be a novel target for the treatment of DN. Podocyte apoptosis is important mechanism that leading to proteinuria in Diabetic nephropathy (DN), but the underling mechanisms that cause podocyte apoptosis in DN are not very clear. We have recently demonstrated that RhoA, a small GTPase protein, effectively protected podocyte apoptosis induced by LPS and ADR in vitro. However, the potential role of RhoA in DN is unknown.
[en] Eight modifications of the ''universal'' medium are proposed, differing one from another by the method of preparing glucose. Thioglycolane and Saburo media were used as controls. All experiments were conducted in Petri dishes. It has been found that the ''universal'' medium can be improved by increasing glucose up to 1% and lowering sterilization temperature to 1080C (for glucose-enriched media). The ''universal'' medium was then compared with other media by calculating ID50 (50% infectivity dose). The results obtained for S.faecium A2I,B.pumilus E601, Bsphaericus C1A, B.subtilis 6633, S.aureus 209P, C.albicans L-45, and Cl.sporogenes 477 have confirmed the suitability of the ''universal'' medium for use in radiosterilization studies.(author)
[en] To analyze the relation between serum glucose concentration and hospital outcome across the critically ill patients. A single-centre, retrospective study was performed at surgical and medical intensive care unit. Admission glucose, mean morning glucose, mean glucose, maximal glucose and time-averaged glucose levels were calculated for each patient. The time-averaged hyperglycemia was defined as the area under the curve above the upper limit of normal, divided by the total length of stay. Of 300 patients with a median stay of 16 days, the mortality rate was 32%. Mean fasting glucose was 121 mg/dl in survivors versus 160 mg/dl in non survivors (P=0.001). Mean admission glucose was 127 mg/dl in survivors versus 142 mg/dl in non survivors (0.03). Median time-averaged hyperglycemia was 4 mg/dl in survivors versus 17.5 mg/dl in non survivors (P < 0.006). The area under the receiver operator characteristic (ROC) curve was 0.59 for time-averaged glucose and 0.73 for mean fasting glucose. Whereas time-averaged hyperglycemia is a useful assessment for glucose control in critically ill patients, it has no priority to admission glucose and mean fasting glucose for outcome prediction. (author)
[en] The feasibility of glycosylation post-purification has been demonstrated by introducing glucose into the model protein lysozyme via a novel reaction that is compatible with biological samples. The crystallization of glycoproteins is one of the challenges to be confronted by the crystallographic community in the frame of what is known as glycobiology. The state of the art for the crystallization of glycoproteins is not promising and removal of the carbohydrate chains is generally suggested since they are flexible and a source of heterogeneity. In this paper, the feasibility of introducing glucose into the model protein hen egg-white lysozyme via a post-purification glycosylation reaction that may turn any protein into a model glycoprotein whose carbohydrate fraction can be manipulated is demonstrated
[en] Currently, there are lots of herbal products available in local markets that are used for treatment of diabetes mellitus. Most of these products are not standardized and lack of efficacy and safety data. DiaBetterTM is one of the local herbal products that have been used for treatment of diabetes. This study was carried out to determine the efficacy of DiaBetterTM in reducing hyperglycemia and to elucidate the mechanisms by which hyperglycemia is reduced. Antihyperglycemic evaluation was done in normal and streptozotocin-induced diabetic rats at different prandial states and the antihyperglycemic mechanisms elucidation was carried out in muscle and adipocytes cells using glucose tracer method (2-deoxy-[1-3H]-glucose). The results showed that DiaBetterTM significantly reduced post meal hyperglycemia in normal and diabetic rats, and improved glucose tolerance activity in diabetic rats particularly after 4 and 6 hours of administration. Antihyperglycemic mechanisms elucidation revealed that the DiaBetterTM significantly enhanced insulin-stimulated glucose uptake into adipocytes and muscle cells, with the highest magnitude of enhancement were 1.54-fold (p<0.01) and 1.46-fold (p<0.001), respectively. Molecular mechanisms that responsible for this enhancement were the increment of insulin sensitivity at cells membrane. Cytotoxic evaluation was also done and confirmed that DiaBetterTM was toxicologically safe against muscle and adipocytes cells. In conclusion, post-meal antihyperglycemic and glucose tolerance activity activity of DiaBetterTM was mediated through the enhancement of glucose uptake into adipocytes and muscle cells. Insulin sensitizing activity showed by DiaBetterTM suggests that this product has the potential to ameliorate insulin resistance condition. Therefore, it is suggested that DiaBetterTM can be used as dietary adjunct for the treatment of type 2 diabetes mellitus which related to insulin resistance. (author)
[en] The functional interaction between the peroxisome proliferator-activated receptor γ (PPARγ) and its coactivator PGC-1α is crucial for the normal physiology of PPARγ and its pharmacological response to antidiabetic treatment with rosiglitazone. Here we report the crystal structure of the PPARγ ligand-binding domain bound to rosiglitazone and to a large PGC-1α fragment that contains two LXXLL-related motifs. The structure reveals critical contacts mediated through the first LXXLL motif of PGC-1α and the PPARγ coactivator binding site. Through a combination of biochemical and structural studies, we demonstrate that the first LXXLL motif is the most potent among all nuclear receptor coactivator motifs tested, and only this motif of the two LXXLL-related motifs in PGC-1α is capable of binding to PPARγ. Our studies reveal that the strong interaction of PGC-1α and PPARγ is mediated through both hydrophobic and specific polar interactions. Mutations within the context of the full-length PGC-1α indicate that the first PGC-1α motif is necessary and sufficient for PGC-1α to coactivate PPARγ in the presence or absence of rosiglitazone. These results provide a molecular basis for specific recruitment and functional interplay between PPARγ and PGC-1α in glucose homeostasis and adipocyte differentiation.
[en] The crystal structure of the RBD-PRDI fragment of the antiterminator protein GlcT from Bacillus subtilis has been solved at 2 Å resolution. The structure represents an inactive state of the protein. GlcT is a transcriptional antiterminator protein that is involved in regulation of glucose metabolism in Bacillus subtilis. Antiterminator proteins bind specific RNA sequences, thus preventing the formation of overlapping terminator stem-loops. The structure of a fragment (residues 3–170) comprising the RNA-binding domain (RBD) and the first regulatory domain (PRDI) of GlcT was solved at 2.0 Å resolution with one molecule in the asymmetric unit. The two domains are connected by a helical linker. Their interface is mostly constituted by hydrophobic interactions
[en] Apoptosis plays a critical role in normal vascular development and atherosclerosis. However, high glucose has been reported to generate a certain level of ROS that can inhibit vascular smooth muscle cell (VSMC) apoptosis, with the underlying mechanism remaining unclear. In this study, a synthetic peptide AREGEM (Ala-Arg-Glu-Gly-Glu-Met) exhibited antioxidative effects and was used to investigate its function in VSMCs during hyperglycaemia. MTT assay results demonstrated that AREGEM significantly attenuated high glucose-induced VSMCs proliferation. Flow cytometry displayed that high glucose levels inhibited cell apoptosis, whereas this effect was attenuated by pre-incubation with AREGEM. In addition, the 2′,7'-dichlorofluorescein diacetate (DCFH-DA) fluorescent probe assay further demonstrated that AREGEM reduced intracellular ROS accumulation in VSMCs. Furthermore, this peptide was able to prevent the decrease of caspase-3 activity and the increase of the ratio of Bcl-2/Bax protein in VSMCs exposed to high glucose. These findings demonstrated that AREGEM is able to abolish the effects of high glucose in VSMCs; therefore, this peptide can be a potential candidate to develop a novel strategy for curing diabetic related diseases. - Highlights: • A peptide, AREGEM, can reduce intracellular ROS accumulation in vascular smooth muscle cells (VSMCs). • AREGEM significantly inhibits high glucose-induced proliferation of VSMCs. • AREGEM attenuates the inhibitory effect of high glucose on VSMC Apoptosis and caspase-3 activity. • AREGEM decreases the ratio of Bcl-2/Bax protein in VSMCs exposed to high glucose.
[en] The great challenge for sensor systems to be accepted as a relevant diagnostic and therapeutic tool for cancer detection is the ability to determine the presence of relevant biomarkers or biomarker patterns comparably to or even better than the traditional analytical systems. Biosensor and chemical sensor technologies are already used for several clinical applications such as blood glucose or blood gas measurements. However, up to now not many sensors have been developed for cancer-related tests because only a few of the biomarkers have shown clinical relevance and the performance of the sensor systems is not always satisfactory. New genomic and proteomic tools are used to detect new molecular signatures and identify which combinations of biomarkers may detect best the presence or risk of cancer or monitor cancer therapies. These molecular signatures include genetic and epigenetic signatures, changes in gene expressions, protein biomarker profiles and other metabolite profile changes. They provide new changes in using different sensor technologies for cancer detection especially when complex biomarker patterns have to be analyzed. To address requirements for this complex analysis, there have been recent efforts to develop sensor arrays and new solutions (e.g. lab on a chip) in which sampling, preparation, high-throughput analysis and reporting are integrated. The ability of parallelization, miniaturization and the degree of automation are the focus of new developments and will be supported by nanotechnology approaches. This review recaps some scientific considerations about cancer diagnosis and cancer-related biomarkers, relevant biosensor and chemical sensor technologies, their application as cancer sensors and consideration about future challenges. (topical review)