The Association between Diabetic Retinopathy and Macular Degeneration: A Nationwide Population-Based Study.

OBJECTIVE: Age-related macular degeneration (AMD), particularly its exudative form, is a primary cause of vision impairment in older adults. As diabetes becomes increasingly prevalent in aging, it is crucial to explore the potential relationship between diabetic retinopathy (DR) and AMD. This study aimed to assess the risk of developing overall, non-exudative, and exudative AMD in individuals with DR compared to those without retinopathy (non-DR) based on a nationwide population study in Taiwan. METHODS: A retrospective cohort study was conducted using the Taiwan National Health Insurance Database (NHIRD) (2000-2013). A total of 3413 patients were placed in the study group (DR) and 13,652 in the control group (non-DR) for analysis. Kaplan-Meier analysis and the Cox proportional hazards model were used to calculate the hazard ratios (HRs) and adjusted hazard ratios (aHRs) for the development of AMD, adjusting for confounding factors, such as age, sex, and comorbid conditions. RESULTS: Kaplan-Meier survival analysis indicated a significantly higher cumulative incidence of AMD in the DR group compared to the non-DR group (log-rank test, p < 0.001). Adjusted analyses revealed that individuals with DR faced a greater risk of overall AMD, with an aHR of 3.50 (95% CI = 3.10-3.95). For senile (unspecified) AMD, the aHR was 3.45 (95% CI = 3.04-3.92); for non-exudative senile AMD, it was 2.92 (95% CI = 2.08-4.09); and for exudative AMD, the aHR was 3.92 (95% CI = 2.51-6.14). CONCLUSION: DR is a significant risk factor for both overall, senile, exudative, and non-exudative AMD, even after adjusting for demographic and comorbid conditions. DR patients tend to have a higher prevalence of vascular comorbidities; however, our findings indicate that the ocular pathologies inherent to DR might have a more significant impact on the progression to AMD. Early detection and appropriate treatment of AMD is critically important among DR patients.

Association between amiodarone use and risk of cataract: a population-based active-comparator study.

BACKGROUND: Despite previous concerns about ocular side effects related to amiodarone, the relationship between amiodarone and cataract remains uncertain. Therefore, this study aimed to assess the potential association between amiodarone use and the subsequent risk of cataract, taking into account potential confounders. METHODS: This population-based, active comparator-controlled cohort study utilized the data from the Taiwan National Health Insurance program and involved adults over 40 years old between 2001 and 2013. We analyzed 12 055 new amiodarone users and contrasted them with a propafenone user cohort. The primary outcome was the incidence of cataract. Inverse-probability treatment-weighting (IPTW) was further used to eliminate the potential confounding effects, and Cox proportional-hazard regression analyses were performed to calculate the risk of cataract. Serial subgroup analyses were also performed. RESULTS: In the main analysis, amiodarone users did not exhibit a significant causal relationship in both full cohort [adjusted hazard ratio (aHR): 0.994, 95% confidence interval (CI): 0.913-1.082] and IPTW cohort (IPTW-aHR 0.977, 95% CI: 0.900-1.060). Furthermore, it is important to highlight a significantly reduced risk of cataract among patients with heart failure (IPTW-aHR 0.708, 95% CI: 0.554-0.905) and during the 2-year follow-up period (IPTW-aHR 0.889, 95% CI: 0.794-0.996), implying potential advantages linked to the use of amiodarone. CONCLUSIONS: The study found no increased risk of cataract with amiodarone, one of the most frequently used antiarrhythmic medications, compared to the use of propafenone. Future research is recommended to explore potential mechanisms and their implications for clinical practice.

Influenza vaccination is associated with lower risk of renal cell carcinoma among chronic kidney disease patients: a population-based cohort study.

Background: Chronic kidney disease (CKD) patients possess a higher risk for renal cell carcinoma (RCC) possibly because of related underlying inflammation and immune dysregulation. In the current population-based cohort study, we evaluate the effects of influenza vaccination on RCC among CKD patients. Methods: We analysed the vaccinated and unvaccinated CKD patients (≥55 years of age) identified from the Taiwan National Health Insurance Database. Propensity score matching was used to reduce the selection bias. Subgroup analyses based on comorbid conditions, dialysis status and vaccinated dosages were also conducted. Results: The incidence of RCC decreased significantly in the vaccinated compared with unvaccinated group {unadjusted hazard ratio [HR] 0.50 [95% confidence interval (CI) 0.31-0.81], P < .01; adjusted HR 0.46 [95% CI 0.28-0.75], P < .01}. Such protective effects of influenza vaccination were noted significantly among those ≥75 years of age [unadjusted HR 0.29 (95% CI 0.12-0.74), P < .01; adjusted HR 0.22 (95% CI 0.08-0.58), P < .01]. A reverse association was noted between the total number of vaccinations and RCC events in both unadjusted and adjusted models. The Kaplan-Meier estimates of the RCC events showed significantly higher free survival rates in the vaccinated as compared with the unvaccinated patients (logrank P = .005). Conclusion: This population-based cohort study found a significant inverse relationship between influenza vaccination and the risk of RCC in CKD patients and the protective effects were more prominent in patients >75 years of age. A possible relation exists between the total number of vaccinations and RCC events. Future randomized clinical and basic studies will be needed to prove these findings and underlying pathophysiological mechanisms.

Ultra-thin Ag/Si heterojunction hot-carrier photovoltaic conversion Schottky devices for harvesting solar energy at wavelength above 1.1 µm.

Traditional silicon solar cells can only absorb the solar spectrum at wavelengths below 1.1 µm. Here we proposed a breakthrough in harvesting solar energy below Si bandgap through conversion of hot carriers generated in the metal into a current using an energy barrier at the metal-semiconductor junction. Under appropriate conditions, the photo-excited hot carriers can quickly pass through the energy barrier and lead to photocurrent, maximizing the use of excitation energy and reducing waste heat consumption. Compared with conventional silicon solar cells, hot-carrier photovoltaic conversion Schottky device has better absorption and conversion efficiency for an infrared regime above 1.1 µm, expands the absorption wavelength range of silicon-based solar cells, makes more effective use of the entire solar spectrum, and further improves the photovoltaic performance of metal-silicon interface components by controlling the evaporation rate, deposition thickness, and annealing temperature of the metal layer. Finally, the conversion efficiency 3.316% is achieved under the infrared regime with a wavelength of more than 1100 nm and an irradiance of 13.85 mW/cm2.

Risk of Dry Eye Syndrome in Patients with Orbital Fracture: A Nationwide Population-Based Cohort Study.

This study aimed to investigate whether orbital fracture increases the risk of dry eye syndrome (DES) and identified the profile of prognostic factors. We studied a cohort from the Taiwan National Health Insurance Research Database (NHIRD). Overall, 46,179 and 184,716 participants were enrolled in the study and control groups, respectively. Each patient in the case group was age- and gender-matched to four individuals without orbital fracture that served as the control group. Cox proportional hazards analysis regression was used to estimate the risks of incident DES. During the follow-up period, the case group was more likely to develop incident DES (0.17%) than the control group (0.11%) (p = 0.001). Multivariate Cox regression analysis demonstrated that the case group had a 4.917-fold increased risk of DES compared to the controls. In the stratified age group, orbital fracture had the highest impact on patients aged 18-29 years. Furthermore, patients with orbital roof fracture have a greater risk of developing DES. Regardless of whether having received surgery or not, the patients with orbital fracture have higher risks of DES. Our study demonstrated that orbital fracture increases the risk of developing subsequent DES. Early recognition by thorough examinations with raised awareness in the clinical setting could preserve visual function and prevent further complications.

Prevalence and risk factors for myopia in Taiwanese diabetes mellitus patients: a multicenter case-control study in Taiwan.

This population-based retrospective cohort study investigated the prevalence of myopia among patients with Type 1 and Type 2 diabetes mellitus (DM) and evaluate risk factors for myopia in these groups. Records from 2000 to 2012 with at least one year of follow-up from the Taiwan National Health Insurance Research Database were included. This study included 35,538 patients with DM and 71,076 patients without DM. Patients with DM had a significantly higher adjusted hazard ratio for myopia in all age groups and both sexes compared with patients without DM. The subgroup analysis results revealed that the rates of myopia and astigmatism were significantly higher among patients with DM compared with patients without DM aged < 60 years. However, the rates of high myopia or myopia progression to high myopia did not differ significantly between the two groups. These findings indicate that DM is a critical risk factor for myopia and astigmatism among patients aged < 60 years. Therefore, active surveillance and earlier treatment of myopia are critical for patients with DM.

Author Correction: Angiotensin-converting enzyme inhibitors or angiotensin receptor blocker monotherapy retard deterioration of renal function in Taiwanese chronic kidney disease population.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Author Correction: Relationship between body mass index and renal function deterioration among the Taiwanese chronic kidney disease population.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Very Low-Density Lipoproteins of Metabolic Syndrome Modulates STIM1, Suppresses Store-Operated Calcium Entry, and Deranges Myofilament Proteins in Atrial Myocytes.

Individuals with metabolic syndrome (MetS) are at high risk for atrial myopathy and atrial fibrillation. Very low-density lipoproteins (VLDLs) of MetS (MetS-VLDLs) are cytotoxic to atrial myocytes in vivo and in vitro. The calcineurin-nuclear factor of activated T-cells (NFAT) pathway, which is regulated by stromal interaction molecule 1 (STIM1)/ calcium release-activated calcium channel protein 1 (Orai1)-mediated store-operated Ca2+ entry (SOCE), is a pivotal mediator of adaptive cardiac hypertrophy. We hypothesized that MetS-VLDLs could affect SOCE and the calcineurin-NFAT pathway. Normal-VLDL and MetS-VLDL samples were isolated from the peripheral blood of healthy volunteers and individuals with MetS. VLDLs were applied to HL-1 atrial myocytes for 18 h and were also injected into wild-type C57BL/6 male mouse tails three times per week for six weeks. After the sarcoplasmic reticulum (SR) Ca2+ store was depleted, SOCE was triggered upon reperfusion with 1.8 mM of Ca2+. SOCE was attenuated by MetS-VLDLs, along with reduced transcriptional and membranous expression of STIM1 (P = 0.025), and enhanced modification of O-GlcNAcylation on STIM1 protein, while Orai1 was unaltered. The nuclear translocation and activity of calcineurin were both reduced (P < 0.05), along with the alteration of myofilament proteins in atrial tissues. These changes were absent in normal-VLDL-treated cells. Our results demonstrated that MetS-VLDLs suppressed SOCE by modulating STIM1 at the transcriptional, translational, and post-translational levels, resulting in the inhibition of the calcineurin-NFAT pathway, which resulted in the alteration of myofilament protein expression and sarcomere derangement in atrial tissues. These findings may help explain atrial myopathy in MetS. We suggest a therapeutic target on VLDLs to prevent atrial fibrillation, especially for individuals with MetS.

Diabetic Retinopathy as a Risk Factor for Chronic Kidney Disease Progression: A Multicenter Case⁻Control Study in Taiwan.

It has rarely been studied whether the presence and severity of diabetic retinopathy (DR) could influence the renal disease progression among all chronic kidney disease (CKD) diabetic patients. This study investigates the characteristics of diabetic patients, with different stages of chronic kidney disease (CKD), according to the occurrence of diabetic retinopathy and determines the influence of retinopathy in the deterioration of renal function. We conduct a multicenter, longitudinal cohort study based on the Epidemiology and Risk Factors Surveillance of the CKD project (2008⁻2013) and the National Health Insurance Research Database (NHIRD) (2001⁻2013). A total of 4050 diabetic patients with CKD, 20⁻85 years of age, from 14 hospitals and the community are included in this study. As compared to CKD patients without DR, CKD patients with DR have a lower baseline estimated glomerular filtration rate (eGFR) (39.17 ± 30.36 mL/min per 1.73 m² vs. 54.38 ± 33.67 mL/min per 1.73 m² ); poorer glycemic control (higher glycated hemoglobin (HbA1c) 7.85 ± 4.97 vs. 7.29 ± 4.02, p < 0.01); higher proteinuria (urine protein-to-creatinine ratio (UPCR )1.94 ± 2.96 g/dL vs. 0.91 ± 2.11 g/dL, p < 0.01); more anemia (Hb 11.22 ± 2.43 g/dL vs. 12.39 ± 3.85 g/dL, p < 0.01), and more hypoalbuminemia (3.88 ± 0.95 g/dL vs. 4.16 ± 1.74 g/dL, p < 0.01). Later stage (stage 3b⁻5) CKD patients with DR had significantly higher CKD progression compared with patients without DR (OR (odds ratio) 1.66 (1.36⁻2.02)). Patients with proliferative DR had significantly higher CKD progression events compared to patients with non-proliferative DR (OR 2.18 (1.71⁻2.78)). The presence and severity of DR is a risk factor for CKD progression among our Taiwanese CKD patients with diabetes. Prevention and early detection of DR are important and DR should be routinely screened as early as possible among diabetic CKD patients.

Simultaneous Electrocardiography Recording and Invasive Blood Pressure Measurement in Rats.

For studies related to cardiovascular physiology or pathophysiology, blood pressure (BP) and electrocardiography are basic observational parameters. Research focusing on cardiovascular disease models, potential cardiovascular therapeutic targets or pharmaceutical agents requires assessment of systemic arterial pressure and heart rhythm changes. In situations where radio telemetry systems are not available or affordable, the technique of femoral artery cannulation is an alternative way to obtain intra-arterial pressure waveform recordings and systemic BP measurements. This technique is economical and can be performed with standard equipment in animal facilities. However, invasive arterial pressure recording requires cannulation of small arteries, which can be a challenging surgical skill. Here, we present step-by-step protocols for femoral artery cannulation procedures. Key procedures include the calibration of the data acquisition system, tissue dissection and femoral artery cannulation, and setup of the arterial cannulation system for pressure recording. Surface electrocardiography recording procedures are also included. We also present examples of BP recordings from normotensive and hypertensive rats. This protocol allows reliable direct recordings of systemic BP with simultaneous electrocardiography.

Angiotensin-converting enzyme inhibitors or angiotensin receptor blocker monotherapy retard deterioration of renal function in Taiwanese chronic kidney disease population.

It remains unclear how different uses of angiotensin-converting inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) influence the progression of chronic kidney disease (CKD). This study explored CKD progression in a multicentre, longitudinal cohort study that included 2639 patients with CKD stage 1-5 and hypertension. Patients treated with ACEI or ARB for ≥90 days during a 6-mo period comprised the study group, or no treatment, comprised the control group. The study group was subdivided on the basis of treatment: ACEI monotherapy or ARB monotherapy. Progression of renal deterioration was defined by an average eGFR decline of more than 5 mL/min/1.73 m2/yr or the commencement of dialysis. With at least 1-year follow up, a progression of renal deterioration was demonstrated in 29.70% of the control group and 25.09% of the study group. Patients in the study group had significantly reduced progression of CKD with adjusted odds ratio 0.79 (95% confidence interval: 0.63-0.99). However, when ACEI monotherapy and ARB monotherapy were analyzed separately, none of their associations with CKD progression was statistically significant. In conclusion, ACEI or ARB monotherapy may retard the deterioration of renal function among patients with CKD and hypertension.

Optical coherence tomography angiography in unilateral multifocal choroiditis and panuveitis: A case report.

RATIONALE: Optical coherence tomography angiography (OCT-A) has the advantage to visualize the microvascular structure of the retina in vivo and was utilized clinically in various neovascular retinal diseases. The OCT-A has also been used to examine the lesion in multifocal choroiditis and panuveitis (MCP). This study aimed to describe a case of MCP and present the disease process of a punched-out lesion in the chorioretina with neovascular activity using OCT-A. PATIENTS CONCERNS: A 32-year-old female Caucasian patient presented with a 2-week history of progressive blurred vision in her right eye with photophobia and a diminished temporal visual field. On presentation, her best corrected visual acuity was 6/60 in the right eye with a prominent anterior uveitis seen under slit lamp examination. DIAGNOSES: Dilated fundus examination of the right eye showed vitritis and multiple, punched-out yellowish-white lesions over the peripheral retina. Additional multimodal imaging (MMI) were done including fluorescein angiography (FA), indocyanine green angiography (ICGA) and fundus autofluorescence (FAF), which all revealed characteristic findings of MCP. In general, the diagnosis of unilateral MCP was made. Furthermore, one of the punched-out lesions in the right eye was particularly selected and examined under OCT and OCT-A, which revealed a subretinal elevated lesion with high flow signal under OCT-A. INTERVENTIONS: Treatment with oral prednisolone at 30 mg daily with topical prednisolone acetate 1% every 2 hours were prescribed, which were gradually tapered down within a 2-month course. OUTCOMES: The patient's best corrected visual acuity of the right eye returned to 6/6 at 2 months after the diagnosis. The flow signal in the OCT-A study of the punched-out lesion had also resolved after steroid treatment. LESSONS: The MCP is an uncommon uveitis with multiple inflammatory chorioretinal lesions. Using multimodal imaging technique, physicians can better differentiate these lesions for diagnosis and for further monitoring. Our results demonstrated that these chorioretinal lesions in MCP may display neovascular activities that might not be seen easily using conventional FA or ICGA study. With OCT-A, ophthalmologists could identify and monitor subtle choroidal neovascularization (CNV) changes over these punched-out lesions.

Application of lateral tarsoconjunctival flap to correct ocular complications of Madelung's disease: A case report and literature review.

RATIONALE: Madelung's disease is a specific type of benign symmetric lipomatosis, which is characterized by overgrowing fat distributed at the neck and shoulder. This excessive fat accumulation may occur in different regions, including vital organs, such as the larynx, trachea, or the orbits. Surgery is usually performed to correct the esthetic or functional concern of the affected area. There are only few case reports mentioned about the orbital involvement of this disease. This study aimed to describe a case of Madelung's disease with ocular complications and the successful treatment using tarsoconjunctival flap. PATIENT CONCERNS: A 90-year-old obese male presented with decreased visual acuity accompanied with severe band form punctate epithelial erosions and ciliary injections in both eyes. Exophthalmos and ectropion of the lower eyelids were observed. DIAGNOSES: Orbital computed tomography revealed a rare entity of Madelung's disease with significant massive deposits of lipomas located symmetrically around the orbit and neck region. INTERVENTIONS: Bilateral lateral tarsoconjunctival flaps with lateral tarsal strip procedures were performed to correct the lower eyelid ectropion-related exposure keratopathy. OUTCOMES: The patient obtained improved visual acuity, intact and clear corneal surfaces, and perfect lower eyelid positions over both eyes. LESSONS: Madelung's disease is a rare condition. There are few reports to describe its ocular complications, due to lipoma overgrowing in the orbit. We shared our successful experience to correct ocular complications using tarsoconjunctival flap technique.

Impact of hypoxic and mesopic environments on visual acuity, contrast sensitivity and accommodation in subjects with LASIK surgery and aircrew candidate.

BACKGROUND: The safety of Laser-assisted in situ keratomileusis (LASIK) in aircrew was unclear, in addition, LASIK was not yet approved for aircrew of Taiwan Air Force. This study was aimed to evaluate visual performance in LASIK eyes in hypoxic and twilight environment. METHODS: 48 myopic eyes of 24 subjects enrolled in this study were divided into LASIK group and control group. Subjects were exposed in hypoxic (15% O2) and mesopic (3 cd/m2) environment. Visual performance was evaluated using the Early Treatment of Diabetic Retinopathy Study (ETDRS) visual chart, and Functional Acuity Contrast Test (FACT) before and after the expirement. Physiological parameters of all subjects were measured and recorded throughout the experiment. RESULTS: There was no significant difference of the two groups regarding their age, height, weight, and BMI. There is significant difference of preoperative spherical refractive error between the two groups. The results of physiological parameters were similar between two groups. Under normoxic conditions, there were no significant difference regarding distant vision in photopic and mesopic environments, so as for near vision. As a whole, the contrast sensitivity of the LASIK group were lowered than that of the control group about 35%, under whether normoxic or hypoxic conditions; photopic or mesopic circumstances. Under normoxic conditions, the measured accommodation of the LASIK group were 21% lowered than that of the control group and 31% lowered under hypoxic circumstances. CONCLUSION: There was no significant difference of visual acuity between the two groups regarding hypoxic and mesopic environment, but reduced contrast sensitivity was significant in LASIK group as compared to those of the control group. Accommodation was significantly lowered in LASIK group, compared with control group, in hypoxic environment. Whether postoperative visual performance after LASIK in aircrew during flying duty is safe might need further investigation.

Relationship between body mass index and renal function deterioration among the Taiwanese chronic kidney disease population.

This study investigated the characteristics of patients with different chronic kidney disease (CKD) stages according to various body mass index (BMI) categories and determined the influence of BMI in renal function deterioration. We conducted a multicenter, longitudinal cohort study based on the Epidemiology and Risk Factors Surveillance of CKD project (2008-2013) and National Health Insurance Research Database (2001-2013). A total of 7357 patients with CKD aged 20-85 years from 14 hospitals were included in the study. A higher male sex, diabetes mellitus (DM) and hypertension were noted among overweight and obese CKD patients, while more cancer prevalence was noted among underweight CKD patients. Charlson comorbidity index was significantly higher and correlated with BMI among late CKD patients. Patients with BMI < 18.5 kg/m2 exhibited non-significantly higher events of eGFR decline events in both early and late CKD stages than other BMI groups. BMI alone is not a determinant of CKD progression among our Taiwanese CKD patients. Obesity should be re-defined and body weight manipulation should be individualized in CKD patients.

High fat diet aggravates atrial and ventricular remodeling of hypertensive heart disease in aging rats.

BACKGROUND/PURPOSE: Left ventricular hypertrophy is a major cause of heart failure in aging population. This study is to determine whether an excess dietary fat is lipotoxic or lipoprotein to the hypertrophic aging heart. METHODS: At 44-week-old, a normal chow (12% fat) was replaced a high-fat diet (HFD; 45% fat) for randomly selective spontaneously hypertensive rats (SHR + HFD, n = 6) and Wistar-Kyoto rats (WKY + HFD, n = 6, normotensive control). Others (SHR, n = 11; WKY, n = 10) were continuously fed with normal diets. After 27 weeks, electrocardiogram, echocardiography, and femoral arterial catheterization were performed before rats being sacrificed for molecular biology analyses. RESULTS: HFD aggravated cardiac atrial, ventricular dilation and hypertrophy in SHR (LV mass: SHR + HFD 2026.0 ± 424.9 vs SHR 1449 ± 461.1 mg, unpaired t test P < 0.05). HFD caused significant atrial dilatation in both WKY (LA diameter, 5.38 ± 0.36 vs 4.11 ± 0.42 mm, P < 0.001) and SHR (6.13 ± 0.79 vs 4.69 ± 1.00, P < 0.01). Only in SHR, HFD induced significant left ventricular dilatation (LV diameter, 8.87 ± 1.25 vs 7.08 ± 1.00 mm, P < 0.01) and reduced ejection fraction (LVEF, 62.8 ± 11.6 vs 75.1 ± 9.2 mm, P < 0.05). The α-myosin heavy chain was significantly upregulated in atria and ventricles of HFD groups. HFD induced significant upregulation of PPARα, ACADM, and TNFα transcripts in atrial tissues (P < 0.05). CONCLUSION: Hypertensive heart disease in aging rats was aggravated by HFD with worse atrial, ventricular remodeling and associated with left ventricular systolic function impairment.

Very-Low-Density Lipoprotein of Metabolic Syndrome Modulates Gap Junctions and Slows Cardiac Conduction.

Very-low-density lipoproteins (VLDL) is a hallmark of metabolic syndrome (MetS) and each manifestation of MetS is related to atrial fibrillation (AF) risks. Slowed atrial conduction is a mechanism of AF in MetS. We hypothesized that VLDL can modulate and reduce atrial gap junctions. VLDLs were separated from normal (Normal-VLDL) and MetS (MetS-VLDL) individuals. VLDLs (15 µg/g) and equivalent volumes of saline (CTL) were injected respectively to C57BL/6 mice for 6 weeks. Electrocardiograms demonstrated that MetS-VLDL induced prolongation of P wave (P = 0.041), PR intervals (P = 0.014), QRS duration and QTc interval (both P = 0.003), but Normal-VLDL did not. Optical mapping of perfused hearts confirmed slowed conduction on atria and ventricles of MetS-VLDL mice. Slowed cardiac conduction was associated with significant atrial and ventricular remodeling, along with systolic dysfunction and comparable intra-cardiac fibrosis. MetS-VLDL induced downregulation of Cx40 and Cx43 at transcriptional, translational and tissue levels, and it also enhanced O-GlcNAcylation of Cx40 and Cx43. Protein structure analyses predicted O-GlcNAcylation at serine 18 of Cx40 and Cx43 which may impair stability of gap junctions. In conclusion, MetS-VLDL modulates gap junctions and delays both atrial and ventricular conduction. VLDL may contribute to the pathophysiology of atrial fibrillation and ventricular arrhythmias in MetS.

Effect of microgravity on the mesenchymal stem cell characteristics of limbal fibroblasts.

BACKGROUND: Mesenchymal stem cells (MSCs) are important for regenerative medicine. Limbal fibroblasts (LFs), present in the corneal limbus, have been shown to possess MSC characteristics, and can differentiate into other cell types. The current study sought to investigate the effect of microgravity on the proliferation and differentiation of LFs, and identify culture conditions to obtain a high proportion of LFs possessing MSC characteristics. METHODS: A rotary cell culture system was used to generate microgravity. Cellular proliferation and MSC marker (CD14, CD45, CD90, CD105, and SSEA4) expression were evaluated by WST-1 test and flow cytometry, respectively. Differentiation of LFs into adipocytes, osteocytes, and chondrocytes was examined. The effects of LF-conditioned medium on limbal stem cell differentiation were assessed. RESULTS: The cellular proliferation rates under microgravity were significantly lower than those under normal gravity (0.44 vs. 0.18 at 24 h, and 0.70 vs. 0.44 at 48 h, both P ≤ 0.004). Higher proportions of cells expressed CD90 (95.33% vs 81.69%), CD105 (95.32% vs 87.96%), and SSEA4 (68.26% vs 26.13%) under microgravity than under normal gravity. The differentiation potential of LFs was more prominent under microgravity. The LF-conditioned medium attenuated the differentiation of limbal corneal epithelial stem cells. CONCLUSION: Under microgravity, LFs showed a higher proportion of MSC characteristics and were easily induced into different linage cells. Culture in a microgravity environment may allow harvesting a greater number of MSC-like LFs for stem cell therapy in ocular surface reconstruction.

Deferasirox has strong anti-leukemia activity but may antagonize theanti-leukemia effect of doxorubicin.

Deferasirox (DFX), in addition to its iron-chelation property, has marked anti-proliferative effects on cancer cells. However, the activity and mechanism by which DFX inhibits acute myeloid leukemia (AML) cells remain to be elucidated. Furthermore, the anti-leukemia effect of combining DFX with currently recommended agents doxorubicin (DOX) and cytosine arabinoside (Ara-C) has not been studied. In this study, we show that DFX significantly reduces the viability of three AML cell lines, HL60, THP1, and WEHI3 and two primary leukemic cells harvested from AML patients. DFX induces cell cycle arrest at G1 phase and apoptosis and inhibits phosphorylation of ERK. We also showed that DFX antagonizes the anti-leukemic effect of DOX. On the contrary, combining DFX with Ara-C created a synergistic effect. Our study confirms the anti-leukemia activity of DFX and provides important information on how to select a partner drug for DFX for the treatment of AML in future clinical trials.