scholarly journals Cellular Contractility Profiles of Human Diabetic Corneal Stromal Cells

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Thi N. Lam ◽  
Sarah E. Nicholas ◽  
Alexander Choi ◽  
Jian-Xing Ma ◽  
Dimitrios Karamichos

Diabetic keratopathy is a corneal complication of diabetes mellitus (DM). Patients with diabetic keratopathy are prone to developing corneal haze, scarring, recurrent erosions, and significant wound healing defects/delays. The purpose of this study was to determine the contractility profiles in the diabetic human corneal stromal cells and characterize their molecular signatures. Primary human corneal fibroblasts from healthy, Type 1 DM (T1DM), and Type 2 DM (T2DM) donors were cultured using an established 3D collagen gel model. We tracked, measured, and quantified the contractile footprint over 9 days and quantified the modulation of specific corneal/diabetes markers in the conditional media and cell lysates using western blot analysis. Human corneal fibroblasts (HCFs) exhibited delayed and decreased contractility compared to that from T1DMs and T2DMs. Compared to HCFs, T2DMs demonstrated an initial downregulation of collagen I (day 3), followed by a significant upregulation by day 9. Collagen V was significantly upregulated in both T1DMs and T2DMs based on basal secretion, when compared to HCFs. Cell lysates were upregulated in the myofibroblast-associated marker, α-smooth muscle actin, in T2DMs on day 9, corresponding to the significant increase in contractility rate observed at the same time point. Furthermore, our data demonstrated a significant upregulation in IGF-1 expression in T2DMs, when compared to HCFs and T1DMs, at day 9. T1DMs demonstrated significant downregulation of IGF-1 expression, when compared to HCFs. Overall, both T1DMs and T2DMs exhibited increased contractility associated with fibrotic phenotypes. These findings, and future studies, may contribute to better understanding of the pathobiology of diabetic keratopathy and ultimately the development of new therapeutic approaches.

2014 ◽  
Author(s):  
Abdussalam Elshakmak ◽  
Nuri Shembesh ◽  
Najwa Ali ◽  
Najat Mazig
Keyword(s):  

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 118-LB
Author(s):  
CAROL J. LEVY ◽  
GRENYE OMALLEY ◽  
SUE A. BROWN ◽  
DAN RAGHINARU ◽  
YOGISH C. KUDVA ◽  
...  

Author(s):  
Hetal S. Gusai ◽  
V. K. Kori ◽  
Rajagopala S. ◽  
K. S. Patel ◽  
Ronakgiri V. Gosai

Over the period of time, human race has evolved and till date the development is going on. There is continuous civilization and change in life style of human being. Due to these changes in life style, human being is constantly struggling against the changing environmental conditions to maintain optimum health and vigor throughout the life. These changes have lead to increase in the disease burden in the society. Juvenile Diabetes is also such condition which is going to increase day by day in children. Children are the most vulnerable community in society. Juvenile diabetes (Insulin Dependent Diabetes Mellitus – IDDM/ Type 1 DM / T1DM) is the most common endocrine/metabolic disorder of childhood and adolescence. The high prevalence data of Juvenile Diabetes is also alarming. Globally, the incidence of Type 1 DM is increasing in children and youth by about 3% per annum. It is characterized by deficient insulin production and requires daily parenteral administration of insulin, otherwise may prove fatal. The cause of type 1 diabetes is not known and it is not preventable with current knowledge. So a survey of 50 diagnosed juvenile diabetes patients in Jamnagar city of Gujarat state was conducted. With this survey study an effort has been done to find out some contributory factors in the manifestation of the disease from an Ayurvedic perspective.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jing Lu ◽  
Shan-mei Shen ◽  
Qing Ling ◽  
Bin Wang ◽  
Li-rong Li ◽  
...  

Abstract Background The preservation or restoration of β cell function in type 1 diabetes (T1D) remains as an attractive and challengeable therapeutic target. Mesenchymal stromal cells (MSCs) are multipotent cells with high capacity of immunoregulation, which emerged as a promising cell-based therapy for many immune disorders. The objective of this study was to examine the efficacy and safety of one repeated transplantation of allogeneic MSCs in individuals with T1D. Methods This was a nonrandomized, open-label, parallel-armed prospective study. MSCs were isolated from umbilical cord (UC) of healthy donors. Fifty-three participants including 33 adult-onset (≥ 18 years) and 20 juvenile-onset T1D were enrolled. Twenty-seven subjects (MSC-treated group) received an initial systemic infusion of allogeneic UC-MSCs, followed by a repeat course at 3 months, whereas the control group (n = 26) only received standard care based on intensive insulin therapy. Data at 1-year follow-up was reported in this study. The primary endpoint was clinical remission defined as a 10% increase from baseline in the level of fasting and/or postprandial C-peptide. The secondary endpoints included side effects, serum levels of HbA1c, changes in fasting and postprandial C-peptide, and daily insulin doses. Results After 1-year follow-up, 40.7% subjects in MSC-treated group achieved the primary endpoint, significantly higher than that in the control arm. Three subjects in MSC-treated group, in contrast to none in control group, achieved insulin independence and maintained insulin free for 3 to 12 months. Among the adult-onset T1D, the percent change of postprandial C-peptide was significantly increased in MSC-treated group than in the control group. However, changes in fasting or postprandial C-peptide were not significantly different between groups among the juvenile-onset T1D. Multivariable logistic regression assay indicated that lower fasting C-peptide and higher dose of UC-MSC correlated with achievement of clinical remission after transplantation. No severe side effects were observed. Conclusion One repeated intravenous dose of allogeneic UC-MSCs is safe in people with recent-onset T1D and may result in better islet β cell preservation during the first year after diagnosis compared to standard treatment alone. Trial registration ChiCTR2100045434. Registered on April 15, 2021—retrospectively registered, http://www.chictr.org.cn/


2021 ◽  
Vol 22 (4) ◽  
pp. 2216
Author(s):  
Cheng-Chia Yu ◽  
Yi-Wen Liao ◽  
Pei-Ling Hsieh ◽  
Yu-Chao Chang

Oral submucous fibrosis (OSF) is known as a potentially malignant disorder, which may result from chemical irritation due to areca nuts (such as arecoline). Emerging evidence suggests that fibrogenesis and carcinogenesis are regulated by the interaction of long noncoding RNAs (lncRNAs) and microRNAs. Among these regulators, profibrotic lncRNA H19 has been found to be overexpressed in several fibrosis diseases. Here, we examined the expression of H19 in OSF specimens and its functional role in fibrotic buccal mucosal fibroblasts (fBMFs). Our results indicate that the aberrantly overexpressed H19 contributed to higher myofibroblast activities, such as collagen gel contractility and migration ability. We also demonstrated that H19 interacted with miR-29b, which suppressed the direct binding of miR-29b to the 3′-untranslated region of type I collagen (COL1A1). We showed that ectopic expression of miR-29b ameliorated various myofibroblast phenotypes and the expression of α-smooth muscle actin (α-SMA), COL1A1, and fibronectin (FN1) in fBMFs. In OSF tissues, we found that the expression of miR-29b was downregulated and there was a negative correlation between miR-29b and these fibrosis markers. Lastly, we demonstrate that arecoline stimulated the upregulation of H19 through the transforming growth factor (TGF)-β pathway. Altogether, this study suggests that increased TGF-β secretion following areca nut chewing may induce the upregulation of H19, which serves as a natural sponge for miR-29b and impedes its antifibrotic effects.


Author(s):  
Umamaheswari Gurunathan ◽  
Hemchand Krishna Prasad ◽  
Sherline White ◽  
Bala Prasanna ◽  
Thangavelu Sangaralingam

AbstractObjectivesPaucity of data from India on care of children with Type 1 diabetes in schools. Aims: To study assess the knowledge, attitude, practices and fear of Type 1 diabetes in school teachers and to assess the impact of an educational model on the fear of teachers and care of children in Type 1 DM at school hours.MethodsA community based study, involving school teachers and the intervention being educating them about diabetes conducted. Data pertaining to basic demography, attitude of teachers towards diabetic children, Hypoglycemia fear factor survey- parent version with worries domain and preparedness of school was collected. An education program was conducted on diabetes care in children. Immediately and after three months, the proforma details and HFSP-W scores reassessed.ResultsForty two teachers (mean age: 38.7±5.4; M:F ratio 2:40) participated in the study. Post intervention, a higher willingness to have the diabetic child in class (100 vs. 57.1%; p>0.05), better support in daily care (100 vs. 92%; p>0.05), participation in sports activities (100 vs. 7.1%; p<0.05) observed. HFSP-W scores were 38.8±4.5 (pre-intervention), 22.5±4.3 (immediate post intervention) and 29.5±3.2 (at 3months) (p<0.05). To study the determinants of improvement in HFSP-W a regression analysis was performed: presence of glucometer the most likely determining factor (T=1.999, p=0.05).ConclusionThere is a significant element of fear in the minds of teachers towards hypoglycemia which improves with a structured education program.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Junichi Mukai ◽  
Shinya Kanno ◽  
Rie Kubota

AbstractThe safety profiles of sodium-glucose co-transporter 2 (SGLT2) inhibitors may depend on races/ethnicities. We aimed to assess the safety profiles of SGLT2 inhibitors in Japanese patients with diabetes mellitus (DM). The electronic databases MEDLINE, CENTRAL, and Ichushi-web were searched for studies with no language restriction from their inception to August 2019. Trials were included in the analysis if they were randomized controlled trials (RCTs) comparing the effects of SGLT2 inhibitors with a placebo in Japanese patients with DM > 18 years and reporting HbA1c and at least 1 adverse event. We calculated risk ratios with 95% CIs and used a random-effects model. Of the 22 RCTs included in our review, only 1 included patients with type 1 DM. The durations of RCTs ranged between 4 and 24 weeks. In comparison with a placebo, SGLT2 inhibitors were associated with similar risks of hypoglycemia, urinary tract infection, genital infection, hypovolemia, and fracture. The outcomes of treatment with SGLT2 inhibitors among Japanese patients with DM suggest favorable safety profiles. However, further evidence from studies with a longer duration, involving more diverse populations, such as patients with different types of DM, or including individual SGLT2 inhibitors is needed to resolve the limitations of the present study.


2021 ◽  
Vol 8 (1) ◽  
pp. 11
Author(s):  
Sorel E. De Leon ◽  
Lana Cleuren ◽  
Zay Yar Oo ◽  
Paul R. Stoddart ◽  
Sally L. McArthur

Three-dimensional (3D) cell cultures have recently emerged as tools for biologically modelling the human body. As 3D models make their way into laboratories there is a need to develop characterisation techniques that are sensitive enough to monitor the cells in real time and without the need for chemical labels. Impedance spectroscopy has been shown to address both of these challenges, but there has been little research into the full impedance spectrum and how the different components of the system affect the impedance signal. Here we investigate the impedance of human fibroblast cells in 2D and 3D collagen gel cultures across a broad range of frequencies (10 Hz to 5 MHz) using a commercial well with in-plane electrodes. At low frequencies in both 2D and 3D models it was observed that protein adsorption influences the magnitude of the impedance for the cell-free samples. This effect was eliminated once cells were introduced to the systems. Cell proliferation could be monitored in 2D at intermediate frequencies (30 kHz). However, the in-plane electrodes were unable to detect any changes in the impedance at any frequency when the cells were cultured in the 3D collagen gel. The results suggest that in designing impedance measurement devices, both the nature and distribution of the cells within the 3D culture as well as the architecture of the electrodes are key variables.


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