Diabetes Coronary Artery Disease Research Articles

Mitochondrial Dynamics and Mitophagy in Cardiometabolic Disease.

Mitochondria play a key role in cellular metabolism. Mitochondrial dynamics (fusion and fission) and mitophagy, are critical to mitochondrial function. Fusion allows organelles to share metabolites, proteins, and mitochondrial DNA, promoting complementarity between damaged mitochondria. Fission increases the number of mitochondria to ensure that they are passed on to their offspring during mitosis. Mitophagy is a process of selective removal of excess or damaged mitochondria that helps improve energy metabolism. Cardiometabolic disease is characterized by mitochondrial dysfunction, high production of reactive oxygen species, increased inflammatory response, and low levels of ATP. Cardiometabolic disease is closely related to mitochondrial dynamics and mitophagy. This paper reviewed the mechanisms of mitochondrial dynamics and mitophagy (focus on MFN1, MFN2, OPA1, DRP1, and PINK1 proteins) and their roles in diabetic cardiomyopathy, myocardial infarction, cardiac hypertrophy, heart failure, atherosclerosis, and obesity.

The Causal Effect of Systolic Blood Pressure Lowering on Vascular Outcomes in Diabetes: A Mendelian Randomization Study.

The effect of lowering systolic blood pressure (SBP) on clinical outcomes in diabetic patients is controversial. We used 2-sample mendelian randomization (MR) to study the causal effect of decreasing SBP on the risk of macrovascular and microvascular outcomes in diabetic patients. We used 362 SBP-related genetic variants from a large genome-wide association study (n = 299 024) and UK Biobank (n = 375 256) as exposure. We evaluated 5 macrovascular and microvascular complications up to 60 742 cases as outcomes in diabetes, including coronary artery disease (CAD), peripheral artery disease (PAD), nephropathy, retinopathy, and composite complications. All cases were diagnosed together with diabetes. We performed follow-up analyses by conducting 7 sensitivity analyses and comparing the present MR with results in general population, and clinical trials. Genetic predisposition of each 10-mm Hg SBP decrease was significantly associated with a 28% decreased risk of CAD (odds ratio [OR]: 0.72; 95% CI, 0.59-0.89; P = .002), a 34% decreased risk of nephropathy (OR: 0.66; 95% CI, 0.54-0.81; P < .001), and a 34% decreased risk of the composite complications (OR: 0.66; 95% CI, 0.58-0.76; P < .001), and was nominally associated with a decreased risk of PAD (OR: 0.69; 95% CI, 0.48-0.99) and retinopathy (OR: 0.90; 95% CI, 0.81-0.99). The MR results in diabetes were similar with that in the general population and clinical trials. SBP lowering was causally associated with an attenuated risk of diabetic CAD and nephropathy. It provides genetic evidence for the beneficial effect of lifelong SBP control in preventing diabetes-related vascular outcomes.

Guidelines on models of diabetic heart disease.

Diabetes is a major risk factor for cardiovascular diseases, including diabetic cardiomyopathy, atherosclerosis, myocardial infarction, and heart failure. As cardiovascular disease represents the number one cause of death in people with diabetes, there has been a major emphasis on understanding the mechanisms by which diabetes promotes cardiovascular disease, and how antidiabetic therapies impact diabetic heart disease. With a wide array of models to study diabetes (both type 1 and type 2), the field has made major progress in answering these questions. However, each model has its own inherent limitations. Therefore, the purpose of this guidelines document is to provide the field with information on which aspects of cardiovascular disease in the human diabetic population are most accurately reproduced by the available models. This review aims to emphasize the advantages and disadvantages of each model, and to highlight the practical challenges and technical considerations involved. We will review the preclinical animal models of diabetes (based on their method of induction), appraise models of diabetes-related atherosclerosis and heart failure, and discuss in vitro models of diabetic heart disease. These guidelines will allow researchers to select the appropriate model of diabetic heart disease, depending on the specific research question being addressed.

Biejiajian Pill Ameliorates Diabetes-Associated Atherosclerosis through Inhibition of the NLRP3 Inflammasome.

Objective To research the efficacy of Biejiajian pill (BJJ) on diabetes-associated atherosclerosis and explore its subsequent mechanisms. Methods Diabetes-associated atherosclerosis (AS) was established in apolipoprotein E knockout (ApoE−/−) mice using high-fat diet and streptozotocin. Atorvastatin (ATV, 10 mg/kg/day) or BJJ-L (BJJ low-dose, 0.9 g/kg/day), BJJ-M (BJJ medium-dose, 1.8 g/kg/day), and BJJ-H (BJJ high-dose, 3.6 g/kg/day) were administered to diabetic ApoE−/− mice for 12 continuous weeks. The normal control group consisted of 10 male C57BL/6J mice. Atherosclerosis plaques, vascular endothelial function, fasting blood glucose, lipid metabolism, inflammatory factors, NLRP3 inflammasome expression, and mitochondria and autophagy changes were evaluated. Results The atherosclerotic lesions areas in the aortas were analyzed through Oil Red O and H&E staining, and they were reduced in the BJJ-H and BJJ-M groups. In the BJJ group, endothelin-1 (ET-1) levels were decreased, whereas endothelial nitric oxide synthase (eNOS) was increased. Fasting blood glucose levels in the BJJ and ATV groups were gradually decreased. Lipid metabolism parameters such as TG, TC, and LDL-C were reduced, while HDL-C was elevated in BJJ groups. The serum IL-1β and IL-18 were decreased under BJJ therapy. The aortic mRNA and protein expressions of NF-κB, TXNIP, NLRP3, ASC, caspase-1, and IL-1β were inhibited in BJJ-H and BJJ-M groups, especially in the BJJ-H group. Electron microscopy revealed an increase in autophagy in each treatment group. Conclusions The findings reveal that BJJ could alleviate diabetic atherosclerosis in diabetic ApoE−/− mice by inhibiting NLRP3 inflammasome.

Obesity is associated with severe COVID-19

Diabetes mellitus, hypertension, and coronary artery disease (CAD) are comorbidities for severe COVID-19. Recently, there has been higher need for admission to intensive care unit (ICU), requiring oxygen support with high flow nasal cannula (HFNC), non-invasive ventilation (NIV), and invasive mechanical ventilation (IMV) amongst COVID-19 patients with obesity. The relationship between obesity and severe dyspnoea in COVID-19 needs more investigation.

Obesity and cancer: the gammadelta T cell link

Obesity has become a worldwide scourge, affecting more than 10% of adults worldwide. While widely recognized to be associated with increased incidence of medical conditions such as diabetes mellitus and atherosclerosis, obesity also accounts for 9% of the cancer burden in some populations. This is due in part to perturbation of protective immune mechanisms involving natural killer cells, macrophages, and neutrophils. Recent studies indicate that γδ T cells play a prominent protective role against cancer, but in some circumstances are detrimental and pro tumorogenic. In this review, the current scientific literature was explored to determine whether and how obesity affects the anti- and pro-tumoral functions of γδ T cells. Considerable perturbations of γδ T cells by obesity were revealed, suggesting that the “obesity-γδ T cell axis” may profoundly impact the increased incidence of cancer in obese individuals and is worthy of further study.

Comparison of continuous subcutaneous insulin infusion treatment and multiple daily injection treatment on the progression of diabetic complications in Japanese patients with juvenile-onset type 1 diabetes mellitus.

ABSTRACTTo evaluate whether continuous subcutaneous insulin infusion attenuates the progression of diabetic complications, we retrospectively extracted data from 35 individuals who had developed type 1 diabetes mellitus aged ≤20 years and whose treatment had been changed from multiple daily injections to continuous subcutaneous insulin infusion. The annual changes in estimated glomerular filtration rate, urinary albumin excretion rate, carotid intima‐media thickness and brachial‐ankle pulse wave velocity during each treatment period were calculated. Although mean glycated hemoglobin under the continuous subcutaneous insulin infusion treatment was lower than that under the multiple daily injection treatment, there were no significant differences in annual changes in diabetic nephropathy and atherosclerosis between the two treatment periods. This pilot study showed that, in Japanese patients with juvenile‐onset type 1 diabetes mellitus, there was no significant difference in the progression of diabetic nephropathy and atherosclerosis, at least in the early stage, between the two treatments.

Circulating Soluble ACE2 Plays an Independent Role to Protect against Vascular Damage in Diabetic Mice.

Circulating levels of soluble ACE2 are increased by diabetes. Although this increase is associated with the presence and severity of cardiovascular disease, the specific role of soluble ACE2 in atherogenesis is unclear. Previous studies suggested that, like circulating ACE, soluble ACE2 plays a limited role in vascular homeostasis. To challenge this hypothesis, we aimed to selectively increase circulating ACE2 and measure its effects on angiotensin II dependent atherogenesis. Firstly, in Ace2/ApoE DKO mice, restoration of circulating ACE2 with recombinant murine soluble (rmACE219-613; 1 mg/kg/alternate day IP) reduced plaque accumulation in the aortic arch, suggesting that the phenotype may be driven as much by loss of soluble ACE2 as the reduction in local ACE2. Secondly, in diabetic ApoE KO mice, where activation of the renin angiotensin system drives accelerated atherosclerosis, rmACE219-613 also reduced plaque accumulation in the aorta after 6 weeks. Thirdly, to ensure consistent long-term delivery of soluble ACE2, an intramuscular injection was used to deliver a DNA minicircle encoding ACE219-613. This strategy efficiently increased circulating soluble ACE2 and reduced atherogenesis and albuminuria in diabetic ApoE KO mice followed for 10 weeks. We propose that soluble ACE2 has independent vasculoprotective effects. Future strategies that increase soluble ACE2 may reduce accelerated atherosclerosis in diabetes and other states in which the renin angiotensin system is upregulated.

Prevalence and impact of high BMI in CAD patients

Abstract Funding Acknowledgements Type of funding sources: None. Background High body mass index (BMI) is a precursor to coronary artery disease (CAD) and an aggravator of the other co-existing CAD risk factors such as diabetes and hypertension. Lifestyle changes (e.g. balanced diet and exercise) in patients with high BMI are usually overlooked, although they contribute positively to prevention and improvement of CAD. Purpose The aim of this study is to calculate the prevalence of overweight and obesity in known CAD patients in both genders, in correlation with diabetes, hypertension, exercise and diet in CAD patients and to compare the findings to EUROASPIRE IV conducted in 2015 (1). Methods This study retrospectively included 362 patients (88% male; mean age 67 years) with a history of CAD (MI, PCI or CABG) from the registry of Cyprus heart survey in a hospital, in Nicosia from 2011 to 2014. Age, gender, date of myocardial infarction event, date of PCI or CABG surgery as well as CAD risk factors such as BMI, exercise, diet, hypertension and diabetes were noted on their visit to the cardiac clinic. Results Our study showed an overall similarity in BMI prevalence across both genders. The prevalence increased from 17.7% in patients with normal BMI (18.5-24.9) to the highest CAD prevalence of 49.2% which was seen in overweight (BMI = 25 –29.9) patients. However, there was a drop in the prevalence of obese (BMI = 30+) patients to 32.9%. This is supported by EUROASPIRE IV (1) which highlighted that CAD prevalence was higher in overweight patients (male = 83%; female = 80%) than obese patients (male = 36%; female = 44%) by nearly 2-fold. Furthermore, within the higher-than-normal BMIs, we recognized more non-diabetic CAD patients (115 overweight; 67 obese) in our study than diabetic CAD patients (62 overweight; 55 obese). On the contrary, hypertensive CAD patients (106 overweight; 80 obese) were more frequent than non-hypertensive CAD patients (71 overweight; 43 obese). Overweight patients split in nearly half when it came to exercise and diet (96 exercise, 82 do not; 90 diet, 88 do not). While in obese patients there was a higher proportion of patients not exercising or following a diet (47 exercise, 72 do not; 32 diet, 87 do not). According to EUROASPIRE IV (1), obesity contributed to higher prevalence of diabetes as patients did not lose weight. Conclusion Overweight and obese patients make up a large percentage of CAD patients. High BMI had a negative additive effect with hypertension but not with diabetes on the risk prevention in CAD patients which mismatches with the EUROASPIRE IV (1) findings. Despite BMI being a modifiable risk factor, not adhering to a diet or exercise was noticed in overweight and obese patients, which in return weakens their prevention of CAD.

Potential Mechanisms and Effects of Chinese Medicines in Treatment of Diabetic Atherosclerosis by Modulating NLRP3 Inflammasome: A Narrative Review.

Nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) is an intracellular sensor that detects endogenous danger signals and environmental irritants to assemble into the NLRP3 inflammasome. Activation of the NLRP3 inflammasome leads to the secretion of the proinflammatory cytokines interleutkin (IL)-1β and IL-18 and induces pyroptosis. Recent studies have shown that the NLRP3 inflammasome participates in the initiation and progression of diabetic atherosclerosis through pathological mechanisms such as β-cell dysfunction, insulin resistance, endothelial cell dysfunction, monocyte adhesion and infiltration, and smooth muscle cell proliferation and migration. In diabetic atherosclerosis, Chinese medicine has been proven effective for the inflammatory response mediated by the NLRP3 inflammasome. This review summarizes the latest progress on the NLRP3 inflammasome in the pathogenesis and potential Chinese medicine treatment of diabetic atherosclerosis.

MO108: Paraneoplastic Nephrotic Syndrome in a Man with Breast Cancer

Abstract BACKGROUND Nephrotic syndrome is associated with many solid tumours and haematologic malignancies. Membranous nephropathy (MN) is the most commonly reported paraneoplastic glomerulonephritis; about 10% (rate 5–20%) of adults with MN have been reported to have a malignancy [1]. Less frequently, minimal change disease, focal segmental glomerular sclerosis, membranoproliferative and crescentic glomerulonephritis, IgA nephropathy [1] and thrombotic microangiopathy [2] have been associated with cancer. Differentiating primary from secondary glomerular disease in patients with malignancy can be difficult. The probability of a secondary form is higher when the appearance of proteinuria or nephrotic syndrome precedes by few months or develops within a year of cancer diagnosis. The suspicion of paraneoplastic nephropathy is even stronger when tumour remission is associated by significant fall in proteinuria and when recurrence of malignancy is followed by the development of clinical glomerular disease. Solid tumour most commonly associated with glomerular diseases (mainly MN) is lung cancer, followed by prostate and colorectal cancer. Paraneoplastic glomerular diseases are rarely linked to breast cancer. In two reviews, breast cancer was reported only in 3% (5 out of 159 patients) [1] and 8% (6 out of 85 patients) of patients with MN and solid tumours. Breast cancer is the most common malignancy in women, while it is a rare disease in men. Male breast cancers account for less than 1% of all diagnosed cases, and the mean age is usually over 60 years [1]. METHODS We report the case of a breast cancer in a man associated with a paraneoplastic nephrotic syndrome. A 76-year-old man was managed at our renal department since 2016 for chronic kidney disease. He was overweight and affected by non-insulin dependent diabetes mellitus, arterial hypertension and coronary artery disease. Since 2016 to December 2020, he had stable renal function with serum creatinine levels ranging from 2.5 to 3.0 mg/dL and a normal urinary protein excretion rate (100–150 mg/24 h). In March 2021, the patient developed a right periareolar breast swelling, pain and erythema with yellowish nipple discharge. In the same period, a full-blown nephrotic syndrome with heavy proteinuria (8 g/24 h) was observed, and serum creatinine increased to 3.5–4.0 mg/dL. Immunological blood tests were negative, including anti-PLA2R and anti-THSD7A antibodies. A kidney biopsy could not be performed due to bilateral renal cysts. Mammogram examination and ultrasound imaging revealed ductal ectasia and microscopic calcifications at the site of right breast lesion, so a diagnosis of cancer was made. RESULTS In September 2021, the patient underwent radical right mastectomy and histopathological examination confirmed early-stage breast cancer (pT1a, pN0, Mx R0, ER 100%, PgR 0, Ki67 5%, CerbB2 neg). In the following month, the 24-h urinary protein excretion markedly reduced to 1.4 g and the nephrotic syndrome resolved completely, confirming its secondary origin. CONCLUSIONS Paraneoplastic nephrotic syndrome is a rare complication of cancer. Its recognition and detection of an undiagnosed malignancy could be life-saving. To our knowledge, this is the first case reported in literature of paraneoplastic nephrotic syndrome in a man affected by breast cancer.

Molecular Dynamics Simulation and Essential Dynamics of Deleterious Proline 12 Alanine Single-Nucleotide Polymorphism in PPARγ2 Associated with Type 2 Diabetes, Cardiovascular Disease, and Nonalcoholic Fatty Liver Disease.

Background. Peroxisome proliferator-activated receptor-γ (PPARγ) gene is located at 3p25 position. PPARγ functions as the master regulator of glucose homeostasis and lipoprotein metabolism, and recent studies have reported that it is involved in various metabolic diseases such as diabetes mellitus, hyperlipidemia, coronary artery disease (CAD), and nonalcoholic fatty liver disease (NAFLD). PPARγ1 and PPARγ2 are necessary for the development of adipose tissue and insulin sensitivity regulation. But PPARγ2 is the isoform that was controlled in response to nutrient intake and obesity. Methodology. In this study, we used computational techniques to show the impact of Pro12Ala polymorphism on PPARγ2. The 3-D structure of PPARγ2 was modeled using I-TASSER server. The modeled structure was validated with the ZLab server, and the mutation was created with SPDB viewer. Stability prediction tools were used. Molecular dynamics simulation (MDS) was used to understand the structural and functional behavior of the wild type and mutant. Essential dynamics was also applied. Results and Conclusions. Stability prediction tools were showed that this mutation has a destabilizing effect on the PPARγ2 structure. The RMSD, RMSF, Rg, SASA, and DSSP were in line with H-bond results that showed less flexibility in the mutant structure. Essential dynamics was used to verify MDS results. Pro12Ala polymorphism leads to rigidity of the PPARγ2 protein and might disturb the conformational changes and interactions of PPARγ2 and results in type 2 diabetes mellitus (T2DM), CAD, and NAFLD. This study can help scientists to develop a drug therapy against these diseases.

High Body Mass Index and Change in Cervical Carotid Artery Position on Serial Scans: A Retrospective Study of an Unexplained Phenomenon.

The purpose of this study was to investigate the relationship between increased body mass index (BMI) and abdominal circumference and prevalence of the change of position of common and internal carotid arteries on serial imaging, termed wandering carotid artery. We retrospectively reviewed computed tomography/magnetic resonance imaging neck scans and determined whether the common and internal carotid arteries moved in position on serial scans. We correlated patients' demographic and medical information along with abdominal circumference, BMI, location of the aortic arch, and area of soft tissue surrounding the carotid arteries with the prevalence of a wandering carotid artery. Computed tomography/magnetic resonance imaging neck performed on 56 randomly selected patients between 2017 and 2020 were reviewed. A total of 42.9% of the patients had a wandering common or internal carotid artery. The abdominal circumference and BMI were significantly higher in the patients with wandering carotid arteries compared with the patients without (abdominal circumference = 102.9 ± 14.13 vs 91.61 ± 13.9 cm [ P = 0.01] and BMI = 34.27 ± 8.58 [obese] vs 26.21 ± 4.89 [overweight, P = 0.0001]). After adjusting for age, sex, hypertension, diabetes, atherosclerosis grade, and aortic arch location, the odds of wandering carotid artery was 1.23 (95% confidence interval, 1.1-1.44) times higher for every one-unit increase in BMI. There is a higher prevalence of wandering common and internal carotid arteries in obese patients with large abdominal circumference irrespective of age, sex, diabetes, hypertension, or carotid atherosclerosis.

Endogenous Protective Factors and Potential Therapeutic Agents for Diabetes-Associated Atherosclerosis.

The complications of macrovascular atherosclerosis are the leading cause of disability and mortality in patients with diabetes. It is generally believed that the pathogenesis of diabetic vascular complications is initiated by the imbalance between injury and endogenous protective factors. Multiple endogenous protective factors secreted by endothelium, liver, skeletal muscle and other tissues are recognized of their importance in combating injury factors and maintaining the homeostasis of vasculatures in diabetes. Among them, glucagon-like peptide-1 based drugs were clinically proven to be effective and recommended as the first-line medicine for the treatment of type 2 diabetic patients with high risks or established arteriosclerotic cardiovascular disease (CVD). Some molecules such as irisin and lipoxins have recently been perceived as new protective factors on diabetic atherosclerosis, while the protective role of HDL has been reinterpreted since the failure of several clinical trials to raise HDL therapy on cardiovascular events. The current review aims to summarize systemic endogenous protective factors for diabetes-associated atherosclerosis and discuss their mechanisms and potential therapeutic strategy or their analogues. In particular, we focus on the existing barriers or obstacles that need to be overcome in developing new therapeutic approaches for macrovascular complications of diabetes.

Liraglutide Alleviates Diabetic Atherosclerosis through Regulating Calcification of Vascular Smooth Muscle Cells.

Background Diabetes mellitus (DM) is a group of metabolic diseases characterized by hyperglycemia, which can induce the development of atherosclerosis (AS). Calcification of vascular smooth muscle cells (VSMCs) exerts an important role in the process of AS. In this study, the effects of liraglutide (LIRA) on VSMC under high-glucose condition and its mechanism were explored. Method After VSMC was treated by high glucose with or without LIRA in vitro, the alkaline phosphatase (ALP) activity was measured by the detection kit, osteogenic marker protein expression was detected by Western blotting, and calcification was determined by alizarin red staining. Subsequently, the DM rat model was established and the ALP activity, calcification, and osteogenic marker proteins were determined in vivo. Immunohistochemical (IHC) staining and hematoxylin-eosin staining were performed on the thoracic aorta of DM rats. Result The positive rate of SMα-actin expression in the DM + AS group was significantly lower than that in control rats, but LIRA administration increased the positive rate in the model. The expression of Cbfα-1 and OPN in the DM + AS group was significantly higher than that in the control group, while it was decreased after treatment of LIRA. The ALP activity and calcium content were increased in DM + AS rats, and the treatment of LIRA decreased the phenotypes in the rats, so as to delay the progression of AS in DM rats. Meanwhile, LIRA inhibited the ALP activity, upregulated SM-α expression, and downregulated expression of OPN and Cbfα-1 in VSMC under high-glucose (HG) conditions. Mechanically, HG-enhanced ALP activity, AKT, and ERK phosphorylation were inhibited by LIRA, PI3K antagonist LY294002, or ERK1/2 antagonist PD98059, in which cotreatment of LIRA with LY294002 and PD98059 could further enhance the effect of LIRA on VSMC, and GLP-1R antagonists reversed the phenotypes in the model. LIRA blocked the osteogenic transformation of VSMC through PI3K and ERK1/2 signaling pathways, which can be reversed by GLP-1R antagonists. Conclusion LIRA inhibited the abnormalities in VSMC calcification mediated by the GLP-1R, which was related to PI3K/Akt and ERK1/2 MAPK pathways. Therefore, the prospect and significance of LIRA in the treatment of DM complicated with AS were clarified.

Well-posedness of a mathematical model of diabetic atherosclerosis with advanced glycation end-products

Atherosclerosis is a leading cause of death worldwide; it emerges as a result of multiple dynamical cell processes, including hemodynamics, endothelial damage, innate immunity and sterol biochemistry. Making matters worse, nearly 463 million people have diabetes, which increases atherosclerosis-related inflammation, diabetic patients are twice as likely to have a heart attack or stroke. The pathophysiology of diabetic vascular disease is generally understood. Dyslipidemia with increased levels of atherogenic low-density lipoprotein, hyperglycemia, oxidative stress and increased inflammation are factors that increase the risk and accelerate development of atherosclerosis. In a recent paper, Xie [Well-posedness of a mathematical model of diabetic atherosclerosis. J Math Anal Appl. 2022;505(2):125606], we have developed a mathematical model that includes the effect of hyperglycemia and insulin resistance on plaque growth. In this paper, we propose a more comprehensive mathematical model for diabetic atherosclerosis which include more variables; in particular, it includes the variable for Advanced Glycation End-Products (AGEs) concentration. Hyperglycemia trigger vascular damage by forming AGEs, which are not easily metabolized and may accelerate the progression of vascular disease in diabetic patients. The model is given by a system of partial differential equations (PDEs) with a free boundary. We also establish the local existence and uniqueness of solution to the model. The methodology is to reduce the free boundary to a fixed boundary and the system of PDEs to an abstract evolution equation in Banach spaces, and apply the theory of analytic semigroup.

Dynamics of endocrine and metabolic changes among patients with coronary artery disease, type 2 diabetes mellitus and metabolic syndrome while treating with telmisartan

Dynamics of endocrine and metabolic changes among patients with coronary artery disease, type 2 diabetes mellitus and metabolic syndrome while treating with telmisartan

Larrea divaricata: anti-inflammatory and antioxidant effects on macrophages and low density lipoproteins

BackgroundThe oxidized low density lipoprotein (ox-LDL) contributes to inflammation and oxidative stress through the activation of macrophages under hyperglycemia contributing to the development of diabetes mellitus and to atherosclerosis. Plants are a source of effective and innocuous antioxidants. Larrea divaricata Cav. (Zygophyllaceae) is used in Argentina folk medicine for its anti-inflammatory properties.MethodsThe aim of this work was to study the antioxidant and anti-inflammatory effects of the aqueous extract (AE) of L. divaricata on macrophages under glucose stimulation and on human LDL and HDL particles under free radical generators. ResultsAE reduced the lipid peroxidation (17%), nitric oxide (NO) (47-50%), tumor necrosis factor-α (TNF-α) (32%) and free radicals (50%) induced by glucose on macrophages. Also prevented HDL nitration (28%), thus preserving its function and structure and inhibited LDL oxidation. The effect on the nitrosative stress was mainly driven by nordihydroguaiaretic acid (NDGA).ConclusionsThese results suggest a potential usefulness of AE as an adjuvant phytotherapy in patients with diabetes mellitus and atherosclerosis.

Ensemble Convolutional Neural Network Classification for Pancreatic Steatosis Assessment in Biopsy Images

Non-alcoholic fatty pancreas disease (NAFPD) is a common and at the same time not extensively examined pathological condition that is significantly associated with obesity, metabolic syndrome, and insulin resistance. These factors can lead to the development of critical pathogens such as type-2 diabetes mellitus (T2DM), atherosclerosis, acute pancreatitis, and pancreatic cancer. Until recently, the diagnosis of NAFPD was based on noninvasive medical imaging methods and visual evaluations of microscopic histological samples. The present study focuses on the quantification of steatosis prevalence in pancreatic biopsy specimens with varying degrees of NAFPD. All quantification results are extracted using a methodology consisting of digital image processing and transfer learning in pretrained convolutional neural networks for the detection of histological fat structures. The proposed method is applied to 20 digitized histological samples, producing an 0.08% mean fat quantification error thanks to an ensemble CNN voting system and 83.3% mean Dice fat segmentation similarity compared to the semi-quantitative estimates of specialist physicians.

Examination of New Electrocardiographic Repolarization Markers in Diabetic Patients with Noncritical Coronary Artery Disease.

Background Diabetes mellitus (DM) is a multisystemic, chronic disease that affects many organs. Coronary artery disease (CAD) is the leading cause of death in patients with DM. The electrocardiogram's new ventricular repolarization parameters can predict mortality and morbidity. The ventricular repolarization indices were examined in diabetic patients with a CAD diagnosis in this study. Methods The study group consisted of 84 DM patients (51 males; mean age 58.8 ± 6.6) with noncritical CAD. The control group consisted of 84 DM patients (47 males; mean age 58.7 ± 8.8) with a normal coronary artery. The intervals of QT, QRS, JT, and Tp-e were all measured. Tp-e/QT, Tp-e/QTc, Tp-e/JT, and Tp-e/JTc ratios were determined with QTc, QTd, QTdc, and JTc intervals. Results Heart rate (74.4 ± 13.1 vs. 70.0 ± 13.6 bpm, p: 0.036), QT (381.0 ± 30.3 vs. 368.6 ± 29.1 ms, p: 0.008), QTc (407.5 (359–450) vs. 389 (339–430) ms, p < 0.001), QTd (25.1 ± 6.2 vs. 21.9 ± 9.9 ms, p: 0.013), QTdc (26.7 ± 6.1 vs. 23.1 ± 10.8 ms, p: 0.010), Tp-e (95.7 ± 12.2 vs. 73.6 ± 9.8 ms, p < 0.001), JT (293.8 ± 22.0 vs. 283.5 ± 30.9 ms, p: 0.014), and JTc (313.6 ± 12.3 vs. 302.4 ± 33.7 ms, p=0.005) intervals, and Tp-e/QT (0.25 ± 0.03 vs. 0.20 ± 0.03 ms, p < 0.001), Tp-e/QTc [0.23 (0.19–2.33) vs. 0.19 (0.14–0.25) ms, p=0.007], Tp-e/JT (0.33 ± 0.04 vs. 0.26 ± 0.04 ms, p < 0.001), and Tp-e/JTc (0.30 ± 0.03 vs. 0.24 ± 0.03 ms, p < 0.001) ratios were all found to be significantly higher in diabetic patients with noncritical CAD. Conclusion In this study, ventricular repolarization markers on the surface ECG were found to be elevated in diabetic CAD patients. These variables may be related to fatal arrhythmic events. To be sure, large-scale, randomized controlled trials are required.