Purpose:
The aim of this study was to evaluate whether perivascular space (PVS) severity and retinal ganglion cell layer (GCL) thickness differed based on the stage of diabetic retinopathy (DR) and ...the cognitive status in patients with DR.
Methods:
A total of 81 patients with DR (51 in the non-proliferative group and 30 in the proliferative group) were included in this retrospective, cross-sectional study. PVS severity was assessed in the basal ganglia (BG) and centrum semiovale using MRI. The total cerebral small vessel disease (SVD) score was determined based on the numbers of lacunes and microbleeds and the severity of white matter hyperintensity. Optical coherence tomography was used to measure foveal and perifoveal GCL thicknesses. Cerebral SVD markers and cognitive function were compared between the groups, and correlations between the BG-PVS severity and the Mini-Mental Status Examination (MMSE) scores and GCL parameters were evaluated.
Results:
Patients with proliferative DR had higher BG-PVS severity (
P
= 0.012), higher total cerebral SVD scores (
P
= 0.035), reduced GCL thicknesses in the inferior (
P
= 0.027), superior (
P
= 0.046), and temporal (
P
= 0.038) subfields compared to patients with non-proliferative DR. In addition, the BG-PVS severity was negatively correlated with the MMSE score (
P
= 0.007), and the GCL thickness was negatively correlated with the BG-PVS severity (
P
-values < 0.05 for inferior, superior, and temporal subfields).
Conclusion:
BG-PVS severity and retinal GCL thickness may represent novel imaging biomarkers reflecting the stage of DR and cognitive decline in diabetic patients. Furthermore, these results suggest a possible link between cerebral and retinal neurodegeneration at the clinical level.
The ketogenic pathway is an effective mechanism by which the liver disposes of fatty acids (FAs) to the peripheral tissues. Impaired ketogenesis is presumed to be related to the pathogenesis of ...metabolic-associated fatty liver disease (MAFLD), but the results of previous studies have been controversial. Therefore, we investigated the association between ketogenic capacity and MAFLD in subjects with type 2 diabetes (T2D).
A total of 435 subjects with newly diagnosed T2D was recruited for the study. They were classified into two groups based on median serum β-hydroxybutyrate (β-HB) level: intact
. impaired ketogenesis groups. The associations of baseline serum β-HB and MAFLD indices of hepatic steatosis index, NAFLD liver fat score (NLFS), Framingham Steatosis index (FSI), Zhejian University index, and Chinese NAFLD score were investigated.
Compared to the impaired ketogenesis group, the intact ketogenesis group showed better insulin sensitivity, lower serum triglyceride level, and higher low-density lipoprotein-cholesterol and glycated hemoglobin levels. Serum levels of liver enzymes were not different between the two groups. Of the hepatic steatosis indices, NLFS (0.8
. 0.9, p=0.045) and FSI (39.4
. 47.0: p=0.041) were significantly lower in the intact ketogenesis group. Moreover, intact ketogenesis was significantly associated with lower risk of MAFLD as calculated by FSI after adjusting for potential confounders (adjusted odds ratio 0.48, 95% confidence interval 0.25-0.91, p=0.025).
Our study suggests that intact ketogenesis might be associated with decreased risk of MAFLD in T2D.
Vascular smooth muscle cells (VSMCs) undergo a phenotypic switch from a differentiated to synthetic phenotype in cardiovascular diseases such as atherosclerosis and restenosis. Our previous studies ...indicate that transforming growth factor-β (TGF-β) helps to maintain the differentiated phenotype by regulating expression of pro-differentiation genes such as smooth muscle α-actin (SMA) and Calponin (CNN) through reactive oxygen species (ROS) derived from NADPH oxidase 4 (Nox4) in VSMCs. In this study, we investigated the relationship between Nox4 and myocardin-related transcription factor-A (MRTF-A), a transcription factor known to be important in expression of smooth muscle marker genes. Previous work has shown that MRTF-A interacts with the actin-binding protein, palladin, although how this interaction affects MRTF-A function is unclear, as is the role of phosphorylation in MRTF-A activity. We found that Rho kinase (ROCK)-mediated phosphorylation of MRTF-A is a key event in the regulation of SMA and CNN in VSMCs and that this phosphorylation depends upon Nox4-mediated palladin expression. Knockdown of Nox4 using siRNA decreases TGF-β -induced palladin expression and MRTF-A phosphorylation, suggesting redox-sensitive regulation of this signaling pathway. Knockdown of palladin also decreases MRTF-A phosphorylation. These data suggest that Nox4-dependent palladin expression and ROCK regulate phosphorylation of MRTF-A, a critical factor in the regulation of SRF responsive gene expression.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Generalised Anxiety Disorder (GAD) is a common anxiety-related diagnosis, affecting approximately 5% of the adult population. One characteristic of GAD is a high degree of anxiety sensitivity (AS), a ...personality trait which describes the fear of arousal-related sensations. Here we present a genome-wide association study of AS using a cohort of 730 MZ and DZ female twins. The GWAS showed a significant association for a variant within the RBFOX1 gene. A heritability analysis of the same cohort also confirmed a significant genetic component with h2 of 0.42. Additionally, a subset of the cohort (25 MZ twins discordant for AS) was studied for evidence of differential expression using RNA-seq data. Significant differential expression of two exons with the ITM2B gene within the discordant MZ subset was observed, a finding that was replicated in an independent cohort. While previous research has shown that anxiety has a high comorbidity with a variety of psychiatric and neurodegenerative disorders, our analysis suggests a novel etiology specific to AS.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cancer therapies attempt to destroy the entire tumor, but this tends to require toxic compounds and high doses of radiation. Recently, considerable attention has focused on therapy-induced senescence ...(TIS), which can be induced in cancer cells by low doses of therapeutic drugs or radiation and provides a barrier to tumor development. However, the molecular mechanisms governing TIS remain elusive. Special attention has been paid to the potential chemopreventive effect of aspirin against human colorectal cancer. In this study, we investigated the effects of aspirin on TIS of human colorectal carcinoma (CRC) cells and show that it occurs via sirtuin 1 (SIRT1) and AMP-activated protein kinase (AMPK), two key regulators of cellular metabolism. Aspirin increased the senescence of CRC cells, increased the protein levels of SIRT1, phospho-AMPK (T172), and phospho-acetyl CoA carboxylase (S79), and reduced the cellular level of ATP. Small-interfering RNA-mediated downregulation or pharmacological inhibition of SIRT1 or AMPK significantly attenuated the aspirin-induced cellular senescence in CRC cells. In contrast, treatment with a SIRT1 agonist or an AMP analog induced cellular senescence. Remarkably, SIRT1 knockdown abrogated the aspirin-induced activation of AMPK, and vice versa. During the progression of aspirin-induced cellular senescence in CRC cells, SIRT1 showed increased deacetylase activity at a relatively early time point but was characterized by decreased activity with increased cytoplasmic localization at a later time point. Collectively, these novel findings suggest that aspirin could provide anticancer effects by inducing senescence in human CRC cells through the reciprocal regulation of SIRT1-AMPK pathways.
Aims
Glucagon‐like peptide 1 (GLP-1) receptor agonists have demonstrated strong glycemic control. However, few studies have investigated the effects of switching from insulin to GLP-1 receptor ...agonists. We aimed to investigate, using real-world data, whether switching to dulaglutide improves glycemic control in patients with type 2 diabetes mellitus (T2D) inadequately controlled with conventional insulin treatment.
Materials and methods
We retrospectively evaluated 138 patients with T2D who were switched from insulin to dulaglutide therapy. We excluded 20 patients who dropped out during the follow-up period. The participants were divided into two groups according to whether they resumed insulin treatment at 6 months after switching to a GLP-1 receptor agonist (group I) or not (group II). A multiple logistic regression analysis was performed to evaluate the parameters associated with the risk of resuming insulin after replacement with dulaglutide.
Results
Of 118 patients initiated on the GLP-1 receptor agonist, 62 (53%) resumed insulin treatment (group I), and 53 (47%) continued with GLP-1 receptor agonists or switched to oral anti-hypoglycemic agents (group II). Older age, a higher insulin dose, and lower postprandial glucose levels while switching to the GLP-1 receptor agonist were associated with failure to switch to the GLP-1 receptor agonist from insulin.
Conclusions
A considerable proportion of patients with T2D inadequately controlled with insulin treatment successfully switched to the GLP-1 receptor agonist. Younger age, a lower dose of insulin, and a higher baseline postprandial glucose level may be significant predictors of successful switching from insulin to GLP-1 receptor agonist therapy.
Predictive influences of auditory information on resolution of visual competition were investigated using music, whose visual symbolic notation is familiar only to those with musical training. ...Results from two experiments using different experimental paradigms revealed that melodic congruence between what is seen and what is heard impacts perceptual dynamics during binocular rivalry. This bisensory interaction was observed only when the musical score was perceptually dominant, not when it was suppressed from awareness, and it was observed only in people who could read music. Results from two ancillary experiments showed that this effect of congruence cannot be explained by differential patterns of eye movements or by differential response sluggishness associated with congruent score/melody combinations. Taken together, these results demonstrate robust audiovisual interaction based on high-level, symbolic representations and its predictive influence on perceptual dynamics during binocular rivalry.
Full text
Available for:
BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Chronic wounds in diabetic patients are challenging because their prolonged inflammation makes healing difficult, thus burdening patients, society, and health care systems. Customized dressing ...materials are needed to effectively treat such wounds that vary in shape and depth. The continuous development of 3D‐printing technology along with artificial intelligence has increased the precision, versatility, and compatibility of various materials, thus providing the considerable potential to meet the abovementioned needs. Herein, functional 3D‐printing inks comprising DNA from salmon sperm and DNA‐induced biosilica inspired by marine sponges, are developed for the machine learning‐based 3D‐printing of wound dressings. The DNA and biomineralized silica are incorporated into hydrogel inks in a fast, facile manner. The 3D‐printed wound dressing thus generates provided appropriate porosity, characterized by effective exudate and blood absorption at wound sites, and mechanical tunability indicated by good shape fidelity and printability during optimized 3D printing. Moreover, the DNA and biomineralized silica act as nanotherapeutics, enhancing the biological activity of the dressings in terms of reactive oxygen species scavenging, angiogenesis, and anti‐inflammation activity, thereby accelerating acute and diabetic wound healing. These bioinspired 3D‐printed hydrogels produce using a DNA‐induced biomineralization strategy are an excellent functional platform for clinical applications in acute and chronic wound repair.
The healing of chronic wounds in diabetic patients is challenging due to prolonged inflammation. In this study, bioinspired 3D printing inks comprising of functionalized sodium alginate (FSA), biomineralized silica, and DNA are developed. Bioinspired hydrogel dressings fabricated with DNA‐bSi@FSA inks and the 3D printing process are optimized using machine learning. The potential of using biomineralization‐based nanotherapeutics for chronic wound repair is evaluated.
Full text
Available for:
FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
We developed a set of assessment tools for health professionals to evaluate the physical functions, mental functions, and social abilities of people with stroke (PWS) from 6 months to 3 years after ...stroke onset, to design a tailored "Rehabilitation Exercise and Sports" (RES) program, which the South Korean government was required to provide by the Act on Guarantee of Right to Health and Access to Health Services for people with disabilities. Since previous studies mainly dealt with the chronic stage of PWS, it would not be appropriate to apply assessment tools used in previous studies, as they are not compatible with the time window (6 months to 3 years) used to define the target population of the RES program. We reviewed the literature to identify evaluation factors and assessment tools applied in previous studies, and developed a Delphi questionnaire with closed-ended questions based on the literature review's results and supplementary open-ended questions. A 20-expert panel conducted four rounds of the Delphi survey, including two rounds to determine evaluation factors and two rounds to determine assessment tools. The Delphi survey revealed that 22 evaluation factors and 24 corresponding assessment tools reached consensus among the experts. However, no assessment tools reached consensus for three evaluation factors: muscle endurance, flexibility, and dynamic balance. A comprehensive set of assessment tools would be useful for health professionals to understand the health status of PWS from 6 months to 3 years after stroke onset, and help the design of tailored RES programs.
PDF
