The Biology and Therapeutic Applications of Red Blood Cell Extracellular Vesicles

This chapter focuses on the biology of red blood cell extracellular vesicles (RBCEVs) in normal and diseased conditions, and the potential application of RBCEVs in treatment. Extracellular vesicles (EVs) refer to membranous vesicles secreted by cells into the extracellular environment. EV biology belongs to a rapidly developing field in biomedical sciences. EVs represent a natural mode of cell-to-cell communication, which makes them suitable for delivery of therapeutic agents, such as nucleic acids and proteins, in the body. In particular, RBCEVs feature a wide range of benefits in drug delivery as compared to extracellular vesicles derived from other cell types. In comparison to other delivery systems currently available, RBCEVs are nontoxic, low immunogenic, conveniently obtainable, and easy to use and store. Therefore, RBCEVs boast promising and exceptional advantages in overcoming various limitations of conventional therapeutics

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To evaluate the relationship between circulating adiponectin and insulin sensitivity in patients with hyperthyroid Graves' disease, we studied 19 adult patients with this disease and 19 age-and sex-matched euthyroid controls. All hyperthyroid patients were treated with antithyroid drugs and were re-evaluated after thyroid function normalized. Before antithyroid treatment, the adiponectin plasma concentrations were not different comparing with those in control group. The adiponectin levels remained unchanged after treatment. The homeostasis model assessment of insulin resistance (HOMA-IR) in hyperthyroid group was higher before treatment than after treatment. There was no significant difference in serum glucose and insulin levels between hyperthyroid and control groups and in the hyperthyroid group before and after treatment. BMI-adjusted adiponectin levels were not different among three groups. On the other hand, BMI-adjusted insulin levels and HOMA-IR values were significantly decreased after management of hyperthyroidism. Pearson's correlation revealed that insulin and HOMA-IR values positively correlated with triiodothyronine (T3) and free thyroxine (FT4) levels. However, adiponectin did not correlate with T3, FT4, insulin, HOMA-IR and thyrotropin receptor autoantibody (TRAb) levels. In conclusion, insulin resistance associated with hyperthyroidism is not mediated by the levels of plasma adiponectin

Transcriptional Repressive H3K9 and H3K27 Methylations Contribute to DNMT1-Mediated DNA Methylation Recovery

DNA methylation and histone modifications are two major epigenetic events regulating gene expression and chromatin structure, and their alterations are linked to human carcinogenesis. DNA methylation plays an important role in tumor suppressor gene inactivation, and can be revised by DNA methylation inhibitors. The reversible nature of DNA methylation forms the basis of epigenetic cancer therapy. However, it has been reported that DNA re-methylation and gene re-silencing could occur after removal of demethylation treatment and this may significantly hamper the therapeutic value of DNA methylation inhibitors. In this study we have provided detailed evidence demonstrating that mammalian cells possess a bona fide DNA methylation recovery system. We have also shown that DNA methylation recovery was mediated by the major human DNA methyltransferase, DNMT1. In addition, we found that H3K9-tri-methylation and H3K27-tri-methylation were closely associated with this DNA methylation recovery. These persistent transcriptional repressive histone modifications may have a crucial role in regulating DNMT1-mediated DNA methylation recovery. Our findings may have important implications towards a better understanding of epigenetic regulation and future development of epigenetic therapeutic intervention

Statin use reduces cardiovascular events and all-cause mortality amongst Chinese patients with type 2 diabetes mellitus: a 5-year cohort study

Abstract Background The benefit of statin on the management of Type 2 Diabetes Mellitus (T2DM) among Chinese patients in primary care is not clear nor fully implemented in clinical practice. This study aimed to evaluate and quantify the benefit of statin on the overall cardiovascular risk and all-cause mortality in patients with T2DM. Methods Uncomplicated diabetic patients with baseline low-density-lipoprotein cholesterol (LDL-C) > 2.6 mmol/L and without statin use before baseline in 2010 were followed-up for 5 years for cardiovascular disease (CVD) events and all-cause mortality. Propensity score matching analysis was conducted to identify patients who were newly prescribed statin at baseline and then compared to non-statin users with similar baseline characteristics. Subgroup analysis was done within the statin group to detect any difference in outcomes between patients achieving target LDL-C of <2.6 mmol/L and not. Multivariable Cox proportional hazards regression with adjustment of all baseline covariates was used to evaluate the effect of statin on outcome events. Hazard ratio (HR) and its 95% confidence intervals were reported. Results 10,104 pairs of diabetic patients were propensity score matched. Statin users had an extra drop of 1.21 mmol/L in LDL-C than non-users. Statin group had a CVD incidence rate of 16.533 per 1000 person-years whereas comparison group had 32.387 per 1000 person-years (HR: 0.458) during a median follow-up period of 50.5 months. Statin group had a mortality rate of 8.138 deaths per 1000 person-years whereas comparison group had 19.603 deaths per 1000 person-years (HR: 0.378). For patients prescribed with statin, the HR was 0.491 for CVD and 0.487 for all-cause mortality if target of LDL-C < 2.6 mmol/L achieved compare to those not achieved. Conclusions Use of statin was associated with a significant decrease in CVD risk and all-cause mortality among diabetic patients in primary care, and the risk reduction was most significant if the target of LDL-C less than 2.6 mmol/L was achieved

Creep of parylene-C film

The glass transition temperature of as-deposited parylene-C is first measured to be 50°C with a ramping-temperature-dependent modulus experiment. The creep behavior of parylene-C film in the primary and secondary creep region is then investigated below and above this glass transition temperature using a dynamic mechanical analysis (DMA) machine Q800 from TA instruments at 8 different temperatures: 10, 25, 40, 60, 80, 100, 120 and 150°C. The Burger's model, which is the combined Maxwell model and Kelvin-Voigt model, fits well with our primary and secondary creep data. Accordingly, the results show that there's little or no creep below the glass transition temperature. Above the glass transition temperature, the primary creep and creep rate increases with the temperature, with a retardation time constant around 6 minutes

Drought Stress Priming Improved the Drought Tolerance of Soybean

The capability of a plant to protect itself from stress-related damages is termed &ldquo;adaptability&rdquo; and the phenomenon of showing better performance in subsequent stress is termed &ldquo;stress memory&rdquo;. While drought is one of the most serious disasters to result from climate change, the current understanding of drought stress priming in soybean is still inadequate for effective crop improvement. To fill this gap, in this study, the drought memory response was evaluated in cultivated soybean (Glycine max). To determine if a priming stress prior to a drought stress would be beneficial to the survival of soybean, plants were divided into three treatment groups: the unprimed group receiving one cycle of stress (1S), the primed group receiving two cycles of stress (2S), and the unstressed control group not subjected to any stress (US). When compared with the unprimed plants, priming led to a reduction of drought stress index (DSI) by 3, resulting in more than 14% increase in surviving leaves, more than 13% increase in leaf water content, slight increase in shoot water content and a slower rate of loss of water from the detached leaves. Primed plants had less than 60% the transpiration rate and stomatal conductance compared to the unprimed plants, accompanied by a slight drop in photosynthesis rate, and about a 30% increase in water usage efficiency (WUE). Priming also increased the root-to-shoot ratio, potentially improving water uptake. Selected genes encoding late embryogenesis abundant (LEA) proteins and MYB, NAC and PP2C domain-containing transcription factors were shown to be highly induced in primed plants compared to the unprimed group. In conclusion, priming significantly improved the drought stress response in soybean during recurrent drought, partially through the maintenance of water status and stronger expression of stress related genes. In sum, we have identified key physiological parameters for soybean which may be used as indicators for future genetic study to identify the genetic element controlling the drought stress priming

Common Hemoglobin Variants in Southern Taiwan and Their Effect on the Determination of HbA1c by Ion-exchange High-performance Liquid Chromatography

Patients with hemoglobin (Hb) variants may produce false HbA1c measurement. This study aimed to detect the common Hb variants in southern Taiwan and to evaluate their effect on the determination of HbA1c. Methods: A total of 1,434 samples collected for HbA1c measurement at Kaohsiung Veterans General Hospital in southern Taiwan in March 2008 were submitted for Hb variant analysis by Primus CLC-385. HbA1c measurements were obtained using ion-exchange high-performance liquid chromatography (HPLC) (Tosoh HLC-723 G7) for routine analysis. Patients identified with Hb variants were recalled for boronate-affinity HPLC analysis. The values of estimated average glucose (eAG) were converted from HbA1c. Values of eAG-FPG, calculated by eAG minus fasting plasma glucose (FPG), were compared to estimate the accuracy of HbA1c measurement in patients with Hb variants. Results: Among the 1,434 patients, the mean ± standard deviation of FPG was 162.8 ± 60.5 mg/dL, HbA1c was 8.28 ± 1.97%, and eAG was 190.9 ± 56.6 mg/dL. Five Hb variants were detected in 11 patients, the incidence being 0.76%. Hb J was identified in 4 patients, Hb G in 2 patients, Hb E in 1 patient, Hb owari in 3 patients, and high fetal hemoglobin (HbF) in 1 patient. Abnormal HPLC chromatograms were seen among the patients with Hb J, E, G and HbF, but not in the patients with Hb owari. In patients with Hb variants, FPG was 149.5 ± 39.9 mg/dL, HbA1c was 7.29 ± 2.01%, and eAG was 162.5 ± 57.7 mg/dL. Lower values of eAG-FPG may have occurred in the patients with Hb J and E, and in those with high HbF. On scattergrams of the relationship between HbA1c and FPG, the plots of Hb J, E and high HbF lay below the regression line of non-Hb variants. Inconsistent Hb values between both methods were only observed among some samples of patients with Hb variants. Conclusion: The existence of Hb variants may result in false HbA1c measurement. The possible presence of spuriously low HbA1c levels or abnormal HPLC chromatograms by using ion-exchange methods should be kept in mind

Triboelectric behaviour of selected MOFs in contact with metals

This work was funded by Latvian-Lithuanian-Taiwan Scientific Cooperation Support Fund (LV-LT-TW/2021/3) represented by the Research Council of Lithuania (Project Nr. S-LLT-21-2) and Latvian Council of Science (Project Nr. 03000-3.1.2.1-e/3). Fa-Kuen Shieh would like to thank the Ministry of Science and Technology, Taiwan, for funding support (MOST 110-2923-M-008-002-MY3). Part of the measurements were performed on equipment located at the Center of Excellence at the Institute of Solid State Physics, University of Latvia, which is supported by European Union's Horizon 2020 Framework Programme H2020-WIDESPREAD-01-2016-2017-TeamingPhase2 under Grant Agreement No. 739508, project CAMART2. O. Verners acknowledges support by the European Regional Development Fund within the Activity 1.1.1.2 “Post-doctoral Research Aid” of the Specific Aid Objective 1.1.1 “To increase the research and innovative capacity of scientific institutions of Latvia and the ability to attract external financing, investing in human resources and infrastructure” of the Operational Programme “Growth and Employment” (No.1.1.1.2/VIAA/4/20/636). O. Verners acknowledges Riga Technical University's HPC Center for providing access to their computing infrastructure.MOFs have been effectively used to magnify the triboelectric charge of polymers. However, so far the individual triboelectric properties and charge transfer mechanisms of MOFs haven't been reported. Triboelectric property investigation for selected MOFs show that the main mechanism for MOF triboelectrification in contact with metals is electron transfer. © 2023 The Royal Society of Chemistry.--//-- This is an open access article Šutka A., Shieh F.-K., Kinka M., Lapčinskis L., Chang C.-C., Lam P.K., Pudzs K., Verners O., "Triboelectric behaviour of selected MOFs in contact with metals" (2022) RSC Advances, 13 (1), pp. 41 - 46, DOI: 10.1039/d2ra06150c published under the CC BY and CC BY-NC licence.Latvian-Lithuanian-Taiwan Scientific Cooperation Support Fund (LV-LT-TW/2021/3); Research Council of Lithuania (Project Nr. S-LLT-21-2); Latvian Council of Science (Project Nr. 03000-3.1.2.1-e/3); Ministry of Science and Technology, Taiwan (MOST 110-2923-M-008-002-MY3); ERDF (No.1.1.1.2/VIAA/4/20/636); Institute of Solid-State Physics, University of Latvia has received funding from the European Union's Horizon 2020 Framework Programme H2020-WIDESPREAD-01-2016-2017-Teaming Phase 2 under grant agreement No. 739508, project CAMART2