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Viruses May 2024HIV-associated neurocognitive disorders (HAND) are highly prevalent in those ageing with HIV. High-income country data suggest that vascular risk factors (VRFs) may be...
HIV-associated neurocognitive disorders (HAND) are highly prevalent in those ageing with HIV. High-income country data suggest that vascular risk factors (VRFs) may be stronger predictors of HAND than HIV-disease severity, but data from sub-Saharan Africa are lacking. We evaluated relationships of VRFs, vascular end-organ damage and HAND in individuals aged ≥ 50 in Tanzania. c-ART-treated individuals were assessed for HAND using consensus criteria. The prevalence of VRFs and end organ damage markers were measured. The independent associations of VRFs, end organ damage and HAND were examined using multivariable logistic regression. Data were available for 153 individuals (median age 56, 67.3% female). HAND was highly prevalent (66.7%, 25.5% symptomatic) despite well-managed HIV (70.5% virally suppressed). Vascular risk factors included hypertension (34%), obesity (10.5%), hypercholesterolemia (33.3%), diabetes (5.3%) and current smoking (4.6%). End organ damage prevalence ranged from 1.3% (prior myocardial infarction) to 12.5% (left ventricular hypertrophy). Measured VRFs and end organ damage were not independently associated with HAND. The only significant association was lower diastolic BP ( 0.030, OR 0.969 (0.943-0.997). Our results suggest that vascular risk factors are not major drivers of HAND in this setting. Further studies should explore alternative aetiologies such as chronic inflammation.
Topics: Humans; Female; Male; Tanzania; Middle Aged; Risk Factors; HIV Infections; Aged; Prevalence; AIDS Dementia Complex; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Neurocognitive Disorders
PubMed: 38932112
DOI: 10.3390/v16060819 -
Pharmaceutics Jun 2024Silibinin has considerable therapeutic potential for the treatment of diabetes through anti-inflammatory, antioxidant, and immunomodulatory properties. However, the...
Silibinin has considerable therapeutic potential for the treatment of diabetes through anti-inflammatory, antioxidant, and immunomodulatory properties. However, the therapeutic application of silibinin is quite limited due to its poor bioavailability. In the present study, an attempt was made to improve the antidiabetic efficacy of silibinin by its encapsulation in liposomal vesicles. The liposomes with a high encapsulation efficiency of silibinin (96%) and a zeta potential of -26.2 ± 0.6 mV were developed and studied using nicotinamide/streptozotocin-induced diabetic rats. Administration of silibinin-loaded liposomes to diabetic rats lowered glucose levels, increased insulin levels, and improved pancreatic islet architecture. The anti-inflammatory effect of silibinin-loaded liposomes was demonstrated by a decrease in serum C-reactive protein (CRP) levels and a reduced deposition of collagen fibers in the islets of diabetic rats. Furthermore, silibinin-loaded liposomes were more efficient in lowering glucose, alanine transaminase, triglyceride, and creatinine levels in diabetic rats than pure silibinin. In addition, silibinin-loaded liposomes had a significantly better effect on beta-cell mass and Glut2 glucose receptor distribution in diabetic islets than pure silibinin. The present results clearly show that liposome encapsulation of silibinin enhances its antidiabetic efficacy, which may contribute to the therapeutic benefit of silibinin in the treatment of diabetes and its complications.
PubMed: 38931922
DOI: 10.3390/pharmaceutics16060801 -
Sensors (Basel, Switzerland) Jun 2024The precise segmentation of retinal vasculature is crucial for the early screening of various eye diseases, such as diabetic retinopathy and hypertensive retinopathy....
The precise segmentation of retinal vasculature is crucial for the early screening of various eye diseases, such as diabetic retinopathy and hypertensive retinopathy. Given the complex and variable overall structure of retinal vessels and their delicate, minute local features, the accurate extraction of fine vessels and edge pixels remains a technical challenge in the current research. To enhance the ability to extract thin vessels, this paper incorporates a pyramid channel attention module into a U-shaped network. This allows for more effective capture of information at different levels and increased attention to vessel-related channels, thereby improving model performance. Simultaneously, to prevent overfitting, this paper optimizes the standard convolutional block in the U-Net with the pre-activated residual discard convolution block, thus improving the model's generalization ability. The model is evaluated on three benchmark retinal datasets: DRIVE, CHASE_DB1, and STARE. Experimental results demonstrate that, compared to the baseline model, the proposed model achieves improvements in sensitivity (Sen) scores of 7.12%, 9.65%, and 5.36% on these three datasets, respectively, proving its strong ability to extract fine vessels.
Topics: Humans; Retinal Vessels; Neural Networks, Computer; Algorithms; Microvessels; Image Processing, Computer-Assisted; Diabetic Retinopathy; Retina
PubMed: 38931797
DOI: 10.3390/s24124014 -
Pharmaceuticals (Basel, Switzerland) Jun 2024(1) Background: Globally, about 600 million people are afflicted with diabetes, and one of its most prevalent complications is neuropathy, a debilitating condition. At...
(1) Background: Globally, about 600 million people are afflicted with diabetes, and one of its most prevalent complications is neuropathy, a debilitating condition. At the present time, the exploration of novel therapies for alleviating diabetic-neuropathy-associated pain is genuinely captivating, considering that current therapeutic options are characterized by poor efficacy and significant risk of side effects. In the current research, we evaluated the antihyperalgesic effect the sildenafil (phosphodiesterase-5 inhibitor)-metformin (antihyperglycemic agent) combination and its impact on biochemical markers in alloxan-induced diabetic neuropathy in rats. (2) Methods: This study involved a cohort of 70 diabetic rats and 10 non-diabetic rats. Diabetic neuropathy was induced by a single dose of 130 mg/kg alloxan. The rats were submitted to thermal stimulus test using a hot-cold plate and to tactile stimulus test using von Frey filaments. Moreover, at the end of the experiment, the animals were sacrificed and their brains and livers were collected to investigate the impact of this combination on TNF-α, IL-6, nitrites and thiols levels. (3) Results: The results demonstrated that all sildenafil-metformin combinations decreased the pain sensitivity in the von Frey test, hot plate test and cold plate test. Furthermore, alterations in nitrites and thiols concentrations and pro-inflammatory cytokines (specifically TNF-α and IL-6) were noted following a 15-day regimen of various sildenafil-metformin combinations. (4) Conclusions: The combination of sildenafil and metformin has a synergistic effect on alleviating pain in alloxan-induced diabetic neuropathy rats. Additionally, the combination effectively decreased inflammation, inhibited the rise in NOS activity, and provided protection against glutathione depletion.
PubMed: 38931450
DOI: 10.3390/ph17060783 -
Pharmaceuticals (Basel, Switzerland) Jun 2024Millions of patients suffer from type 1 diabetes (T1D) and its associated complications. Nevertheless, the pursuit of a cure for T1D has encountered significant...
Novel Protein Biomarkers and Therapeutic Targets for Type 1 Diabetes and Its Complications: Insights from Summary-Data-Based Mendelian Randomization and Colocalization Analysis.
Millions of patients suffer from type 1 diabetes (T1D) and its associated complications. Nevertheless, the pursuit of a cure for T1D has encountered significant challenges, with a crucial impediment being the lack of biomarkers that can accurately predict the progression of T1D and reliable therapeutic targets for T1D. Hence, there is an urgent need to discover novel protein biomarkers and therapeutic targets, which holds promise for targeted therapy for T1D. In this study, we extracted summary-level data on 4907 plasma proteins from 35,559 Icelanders and 2923 plasma proteins from 54,219 UK participants as exposures. The genome-wide association study (GWAS) summary statistics on T1D and T1D with complications were obtained from the R9 release results from the FinnGen consortium. Summary-data-based Mendelian randomization (SMR) analysis was employed to evaluate the causal associations between the genetically predicted levels of plasma proteins and T1D-associated outcomes. Colocalization analysis was utilized to investigate the shared genetic variants between the exposure and outcome. Moreover, transcriptome analysis and a protein-protein interaction (PPI) network further illustrated the expression patterns of the identified protein targets and their interactions with the established targets of T1D. Finally, a Mendelian randomization phenome-wide association study evaluated the potential side effects of the identified core protein targets. In the primary SMR analysis, we identified 72 potential protein targets for T1D and its complications, and nine of them were considered crucial protein targets. Within the group were five risk targets and four protective targets. Backed by evidence from the colocalization analysis, the protein targets were classified into four tiers, with MANSC4, CTRB1, SIGLEC5 and MST1 being categorized as tier 1 targets. Delving into the DrugBank database, we retrieved 11 existing medications for T1D along with their therapeutic targets. The PPI network clarified the interactions among the identified potential protein targets and established ones. Finally, the Mendelian randomization phenome-wide association study corroborated MANSC4 as a reliable target capable of mitigating the risk of various forms of diabetes, and it revealed the absence of adverse effects linked to CTRB1, SIGLEC5 and MST1. This study unveiled many protein biomarkers and therapeutic targets for T1D and its complications. Such advancements hold great promise for the progression of drug development and targeted therapy for T1D.
PubMed: 38931433
DOI: 10.3390/ph17060766 -
Pharmaceuticals (Basel, Switzerland) Jun 2024() is a shrub of the Andean Altiplano of Bolivia, Chile and Peru, consumed by local communities as a traditional medicine for several maladies such as diabetes, hepatic...
() is a shrub of the Andean Altiplano of Bolivia, Chile and Peru, consumed by local communities as a traditional medicine for several maladies such as diabetes, hepatic and inflammatory diseases. is rich in mulinane- and azorellane-type diterpenoids. For two of these, acute hypoglycemic effects have been described, but the impact of diterpenoids on fatty liver disease has not been investigated. Therefore, organic fractions were prepared using petroleum ether, dichloromethane and methanol. Their content was characterized by UHPLC/MS, revealing the presence of ten diterpenoids, mainly mulinic acid, azorellanol and mulin-11,13-diene. Next, mice fed with a high-fat diet (HFD), a model of metabolic dysfunction-associated fatty liver disease (MAFLD), received one of the fractions in drinking water for two weeks. After this treatment, hepatic parameters were evaluated. The fractions did not reduce hyperglycemia or body weight in the HFD-fed mice but increased the serum levels of hepatic transaminases (AST and ALT), reduced albumin and increased bilirubin, indicating hepatic damage, while histopathological alterations such as steatosis, inflammation and necrosis generated by the HFD were, overall, not ameliorated by the fractions. These results suggest that organic extracts may generate hepatic complications in patients with MAFLD.
PubMed: 38931413
DOI: 10.3390/ph17060746 -
Pharmaceuticals (Basel, Switzerland) Jun 2024Currently, there is no known cure for diabetes. Different pharmaceutical therapies have been approved for the management of type 2 diabetes mellitus (T2DM), some are in... (Review)
Review
Currently, there is no known cure for diabetes. Different pharmaceutical therapies have been approved for the management of type 2 diabetes mellitus (T2DM), some are in clinical trials and they have been classified according to their route or mechanism of action. Insulin types, sulfonylureas, biguanides, alpha-glucosidase inhibitors, thiazolidinediones, meglitinides, sodium-glucose cotransporter type 2 inhibitors, and incretin-dependent therapies (glucagon-like peptide-1 receptor agonists: GLP-1R, and dipeptidyl peptidase 4 inhibitors: DPP-4). Although some of the currently available drugs are effective in the management of T2DM, the side effects resulting from prolonged use of these drugs remain a serious challenge. GLP-1R agonists are currently the preferred medications to include when oral metformin alone is insufficient to manage T2DM. Medicinal plants now play prominent roles in the management of various diseases globally because they are readily available and affordable as well as having limited and transient side effects. Recently, studies have reported the ability of phytochemicals to activate glucagon-like peptide-1 receptor (GLP-1R), acting as an agonist just like the GLP-1R agonist with beneficial effects in the management of T2DM. Consequently, we propose that careful exploration of phytochemicals for the development of novel therapeutic candidates as GLP-1R agonists will be a welcome breakthrough in the management of T2DM and the co-morbidities associated with T2DM.
PubMed: 38931402
DOI: 10.3390/ph17060736 -
Nutrients Jun 2024Skin autofluorescence (sAF) measurement is a non-invasive method used to assess tissue advanced glycation end product (AGE) accumulation. This study aims to characterize...
Assessment of Skin Autofluorescence and Its Association with Glycated Hemoglobin, Cardiovascular Risk Markers, and Concomitant Chronic Diseases in Children with Type 1 Diabetes.
UNLABELLED
Skin autofluorescence (sAF) measurement is a non-invasive method used to assess tissue advanced glycation end product (AGE) accumulation. This study aims to characterize sAF's association with (1) glycated hemoglobin (HbA1c) values, (2) cardiovascular risk markers, and (3) common comorbidities (autoimmune thyroiditis, celiac disease) in children with type 1 diabetes (T1D).
MATERIALS AND METHODS
A total of 348 children with T1D aged 3-18 years and 85 age- and gender-matched control subjects were enrolled. sAF was quantified using an AGE Reader (Diagnoptics BV, The Netherlands). The analysis covered HbA1c, blood lipid, and C-reactive protein (CRP) levels, ambulatory blood pressure monitoring records, and body composition parameters. The associations between variables and sAF were assessed using the Mann-Whitney U test and Spearman correlation.
RESULTS
We observed significantly higher sAF values in the T1D group compared to the control (1.40 [1.27-1.53] vs. 1.20 [1.07-1.30, AU]; = 0.004), consistent across all tested age groups. In the T1D group, sAF was positively correlated with current HbA1c, mean of historical HbA1c values, and T1D duration (r values, respectively: 0.27, 0.22, 0.14, all < 0.01). Percentage of body fat was positively correlated with sAF (r = 0.120; = 0.044). No significant correlations were found between sAF and lipid fractions, Z-score of BMI, parameters from 24 h ambulatory blood pressure monitoring, or the amount of albumin excreted in urine. sAF was positively correlated with CRP (r = 0.17, < 0.05). sAF was significantly higher in patients with concomitant celiac disease (1.53 [1.43-1.63] vs. 1.40 [1.27-1.53, AU], = 0.001).
CONCLUSION
Among young T1D patients with relatively brief diabetes duration, sAF effectively mirrors prior glycemic control, as presented by historical average HbA1c. However, associations with conventional CV risk markers are not evident. The higher sAF values in patients with celiac disease warrant further exploration.
Topics: Humans; Child; Glycated Hemoglobin; Diabetes Mellitus, Type 1; Female; Male; Adolescent; Skin; Child, Preschool; Glycation End Products, Advanced; Heart Disease Risk Factors; Biomarkers; Cardiovascular Diseases; Chronic Disease; Optical Imaging; C-Reactive Protein; Case-Control Studies; Celiac Disease; Comorbidity
PubMed: 38931293
DOI: 10.3390/nu16121940 -
Nutrients Jun 2024Carbohydrate counting is one of the dietary strategies used for the management of type 1 diabetes (T1DM), and counting proteins and fats allows individuals to achieve...
Carbohydrate counting is one of the dietary strategies used for the management of type 1 diabetes (T1DM), and counting proteins and fats allows individuals to achieve better glycemic and metabolic control, reducing glycemic variability and long-term complications. The aim of this paper is to analyze the factors associated with adherence to the protein- and fat-counting strategy in adults with T1DM. This cross-sectional study was conducted from November 2021 to June 2022 through an online questionnaire. We applied Pearson's Chi-square test with adjusted residual analysis and a binomial logistic regression test using SPSS software, version 24.0, considering < 0.05 as indicative of statistical significance. There was an association between performing protein and lipid counting and having a higher education level, income exceeding three minimum wages, and having adequate glycated hemoglobin. Performing protein and lipid counting increased the chances of having adequate HbA1c by 4.3 times. Protein and lipid counting was a predictor of having adequate HbA1c. The results suggest that considering the practice of counting proteins and fats is important as a strategy to optimize glycemic control.
Topics: Humans; Diabetes Mellitus, Type 1; Male; Adult; Female; Cross-Sectional Studies; Dietary Proteins; Glycated Hemoglobin; Patient Compliance; Middle Aged; Dietary Fats; Glycemic Control; Young Adult; Surveys and Questionnaires; Blood Glucose
PubMed: 38931283
DOI: 10.3390/nu16121930 -
Nutrients Jun 2024Diabetic nephropathy (DN), defined as continuously elevated urinary albumin and a diminished estimated glomerular filtration rate, is a serious complication of both type... (Review)
Review
Diabetic nephropathy (DN), defined as continuously elevated urinary albumin and a diminished estimated glomerular filtration rate, is a serious complication of both type 1 diabetes and type 2 diabetes and is the main cause of end-stage kidney disease. Patients with end-stage renal disease require chronic kidney dialysis and/or a kidney transplantation. Research highlights the role of diet in modulating specific signaling pathways that are instrumental in the progression of DN. Nutrient-sensitive pathways, affected by nutritional compounds and dietary components, offer a novel perspective on the management of DN by influencing inflammation, oxidative stress, and nutrient metabolism. Animal models have identified signaling pathways related to glucose metabolism, inflammation responses, autophagy, and lipid metabolism, while human population studies have contributed to the clinical significance of designing medical and nutritional therapies to attenuate DN progression. Here, we will update recent progress in research into the renoprotective or therapeutic effects of nutritional compounds, and potential nutrition-modulated pathways.
Topics: Diabetic Nephropathies; Humans; Animals; Oxidative Stress; Disease Models, Animal; Diabetes Mellitus, Type 2; Diabetes Mellitus, Type 1; Diet; Signal Transduction
PubMed: 38931271
DOI: 10.3390/nu16121918