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Pharmaceutics Jun 2024DOX/TPOR@CB[7] was synthesized via self-assembly, and its physicochemical properties and ability to generate reactive oxygen species (ROS) were evaluated. The impact of...
DOX/TPOR@CB[7] was synthesized via self-assembly, and its physicochemical properties and ability to generate reactive oxygen species (ROS) were evaluated. The impact of photodynamic therapy on SH-SY5Y cells was assessed using the MTT assay, while flow cytometry analysis was employed to detect cell apoptosis. Confocal laser scanning microscopy was utilized to observe the intracellular distribution of DOX/TPOR@CB[7] in SH-SY5Y cells. Additionally, fluorescence imaging of DOX/TPOR@CB[7] in nude mice bearing SH-SY5Y tumors and examination of the combined effects of photodynamic and chemical therapies were conducted. The incorporation of CB[7] significantly enhanced the optical properties of DOX/TPOR@CB[7], resulting in increased ROS production and pronounced toxicity towards SH-SY5Y cells. Moreover, both the apoptotic and mortality rates exhibited significant elevation. In vivo experiments demonstrated that tumor growth inhibition was most prominent in the DOX/TPOR@CB[7] group. π-π interactions facilitated the binding between DOX and photosensitizer TPOR, with TPOR's naphthalene hydrophilic groups encapsulated within CB[7]'s cavity through host-guest interactions with CB[7]. Therefore, CB[7] can serve as a nanocarrier to enhance the combined application of chemical therapy and photodynamic therapy, thereby significantly improving treatment efficacy against neuroblastoma tumors.
PubMed: 38931942
DOI: 10.3390/pharmaceutics16060822 -
Pharmaceutics May 2024We describe the design, synthesis, and activity of a potent thiourea-bridged backbone cyclic peptidomimetic known as Clarstatin, comprising a 5-amino acid sequence...
We describe the design, synthesis, and activity of a potent thiourea-bridged backbone cyclic peptidomimetic known as Clarstatin, comprising a 5-amino acid sequence (Q/D)-(R/K)-X-X-A-(Gln/Asp)-(Arg/Lys)-AA-AA-Ala-based on a motif called "shared epitope (SE)", specifically present in specific alleles of the gene. This SE binds to a particular site within the proline reach domain (P-domain) of the cell surface-calreticulin (CS-CRT). CS-CRT is a multifunctional endoplasmic reticulum (ER) calcium-binding protein that is located on the cell surface of T cells and triggers innate immune signaling, leading to the development of inflammatory autoimmune diseases. The development of Clarstatin was based on the parent peptide W-G-D-K-S-G-A- derived from the active region of the SE. Following the design based on the cycloscan method, the synthesis of Clarstatin was performed by the Fmoc solid phase peptide synthesis (SPPS) method, purified by HPLC to 96% homogeneity, and its structure was confirmed by LC-MS. Clarstatin reduced calcium levels in Jurkat lymphocyte cultures, ameliorated uveitis in vivo in the experimental autoimmune uveitis (EAU) mice model, and was safe upon acute toxicity evaluation. These findings identify Clarstatin as a promising lead compound for future drug development as a novel class of therapeutic agents in the therapy of uveitis.
PubMed: 38931845
DOI: 10.3390/pharmaceutics16060723 -
Nutrients Jun 2024Systemic lupus erythematosus (SLE) is a complex autoimmune disorder that affects multiple organ systems, with a higher prevalence among women in their reproductive... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Systemic lupus erythematosus (SLE) is a complex autoimmune disorder that affects multiple organ systems, with a higher prevalence among women in their reproductive years. The disease's multifactorial etiology involves genetic, environmental, and hormonal components. Recent studies have highlighted the potential impact of dietary factors, particularly unsaturated fatty acids, on the modulation of SLE due to their anti-inflammatory properties. This meta-analysis aims to evaluate the association between unsaturated fatty acid consumption and the risk, progression, and clinical manifestations of SLE, providing evidence-based guidance for dietary management.
METHODS
We conducted a comprehensive search across major medical databases up to January 2024, focusing on studies that examined the intake of unsaturated fatty acids and the impact of such intake on SLE. Using the PICOS (population, intervention, comparator, outcomes, study design) framework, we included randomized controlled trials and case-control studies, assessing outcomes such as SLE activity, measured by SLE Disease Activity Index (SLEDAI) or the British Isles Lupus Assessment Group (BILAG) index, inflammation biomarkers. Studies were analyzed using either a fixed- or random-effects model based on heterogeneity ( statistic), with sensitivity analyses performed to assess the robustness of the findings.
RESULTS
Our search included 10 studies, encompassing a wide variety of designs and populations. The meta-analysis showed that a diet rich in unsaturated fatty acids is significantly associated with a reduction in SLEDAI scores (pooled SMD) of -0.36, 95% CI: -0.61 to -0.11, = 0.007, indicating a beneficial effect on disease activity. Additionally, we found that unsaturated fatty acid intake has a significant impact on HDL levels, suggesting a positive effect on lipid profiles. However, no significant effects were observed on levels of the inflammatory marker IL-6 or other lipid components (LDL and cholesterol). With minimal heterogeneity among studies ( ≤ 15%), sensitivity analysis confirmed the stability and reliability of these results, highlighting the potential role of unsaturated fatty acids in SLE management.
CONCLUSIONS
This meta-analysis suggests that dietary intake of unsaturated fatty acids may play a positive role in reducing SLE activity and may significantly affect HDL levels without having significant effects on inflammation markers or other lipid profiles. These findings support the inclusion of unsaturated fatty acids in the dietary management of SLE patients, although further research is required to refine dietary recommendations and explore the mechanisms underlying these associations.
Topics: Lupus Erythematosus, Systemic; Humans; Fatty Acids, Unsaturated; Female; Diet; Male; Biomarkers; Adult
PubMed: 38931327
DOI: 10.3390/nu16121974 -
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 -
Nutrients Jun 2024Research on the microbiome has progressed from identifying specific microbial communities to exploring how these organisms produce and modify metabolites that impact a... (Review)
Review
Research on the microbiome has progressed from identifying specific microbial communities to exploring how these organisms produce and modify metabolites that impact a wide range of health conditions, including gastrointestinal, metabolic, autoimmune, and neurodegenerative diseases. This review provides an overview of the bacteria commonly found in the intestinal tract, focusing on their main functional outputs. We explore biomarkers that not only indicate a well-balanced microbiota but also potential dysbiosis, which could foreshadow susceptibility to future health conditions. Additionally, it discusses the establishment of the microbiota during the early years of life, examining factors such as gestational age at birth, type of delivery, antibiotic intake, and genetic and environmental influences. Through a comprehensive analysis of current research, this article aims to enhance our understanding of the microbiota's foundational development and its long-term implications for health and disease management.
Topics: Gastrointestinal Microbiome; Humans; Dysbiosis; Bacteria; Infant, Newborn; Infant; Anti-Bacterial Agents; Biomarkers
PubMed: 38931178
DOI: 10.3390/nu16121823 -
Nutrients Jun 2024Lipid functions can be influenced by genetics, age, disease states, and lifestyle factors, particularly dietary patterns, which are crucial in diabetes management....
Lipid functions can be influenced by genetics, age, disease states, and lifestyle factors, particularly dietary patterns, which are crucial in diabetes management. Lipidomics is an expanding field involving the comprehensive exploration of lipids from biological samples. In this cross-sectional study, 396 participants from a Mediterranean region, including individuals with type 1 diabetes (T1D), type 2 diabetes (T2D), and non-diabetic individuals, underwent lipidomic profiling and dietary assessment. Participants completed validated food frequency questionnaires, and lipid analysis was conducted using ultra-high-performance liquid chromatography coupled with mass spectrometry (UHPLC/MS). Multiple linear regression models were used to determine the association between lipid features and dietary patterns. Across all subjects, acylcarnitines (AcCa) and triglycerides (TG) displayed negative associations with the alternate Healthy Eating Index (aHEI), indicating a link between lipidomic profiles and dietary habits. Various lipid species (LS) showed positive and negative associations with dietary carbohydrates, fats, and proteins. Notably, in the interaction analysis between diabetes and the aHEI, we found some lysophosphatidylcholines (LPC) that showed a similar direction with respect to aHEI in non-diabetic individuals and T2D subjects, while an opposite direction was observed in T1D subjects. The study highlights the significant association between lipidomic profiles and dietary habits in people with and without diabetes, particularly emphasizing the role of healthy dietary choices, as reflected by the aHEI, in modulating lipid concentrations. These findings underscore the importance of dietary interventions to improve metabolic health outcomes, especially in the context of diabetes management.
Topics: Humans; Male; Female; Diabetes Mellitus, Type 2; Adult; Cross-Sectional Studies; Lipidomics; Middle Aged; Diabetes Mellitus, Type 1; Feeding Behavior; Mediterranean Region; Lipids; Diet, Healthy; Diet; Triglycerides; Chromatography, High Pressure Liquid; Diet, Mediterranean; Dietary Patterns; Carnitine
PubMed: 38931159
DOI: 10.3390/nu16121805 -
Molecules (Basel, Switzerland) Jun 2024The extract of , a traditional Chinese medicinal and food homologous plant belonging to the family Orchidaceae, was previously reported to have hypoglycemic and...
The extract of , a traditional Chinese medicinal and food homologous plant belonging to the family Orchidaceae, was previously reported to have hypoglycemic and antioxidant effects. In this study, the direct effects of polysaccharide (DHP) and non-polysaccharide (NDHP) components of , as well as its water extract (DHWE) were compared with that of metformin (an antidiabetic drug) on the gut microbiota (collected from fecal flora) of rats with streptozotocin-induced type 1 diabetes (T1D) using an in vitro fermentation method. The results showed that DHWE, DHP, and NDHP reduced pH and increased bacterial proliferation and short-chain fatty acid (SCFA) content in fermentation broth. DHWE, DHP, NDHP and metformin promoted the production of acetic and propionic acid, acetic acid, propionic acid and butyric acid, and propionic acid, respectively. DHWE, DHP, and NDHP reduced the abundance of (subdominant pathogenic bacteria) and increased the abundance of (dominant beneficial gut bacteria). NDHP also reduced the abundance of (beneficial and conditional pathogenic). Metformin increased the abundance of and reduced the abundance of and . At the genus level, NDHP promoted the proliferation of and and decreased harmful bacteria (e.g., ), and DHP increased the abundance of (opportunistic and usually harmless). By contrast, metformin increased the abundance of harmful bacteria (e.g., ) and reduced the abundance of beneficial bacteria (e.g., ). Our study indicates that DHWE, DHP, and NDHP are potentially more beneficial than metformin on the gut microbiota of T1D rats in vitro.
Topics: Animals; Gastrointestinal Microbiome; Metformin; Dendrobium; Polysaccharides; Rats; Diabetes Mellitus, Type 1; Fatty Acids, Volatile; Hypoglycemic Agents; Plant Extracts; Male; Diabetes Mellitus, Experimental
PubMed: 38930856
DOI: 10.3390/molecules29122791 -
Journal of Clinical Medicine Jun 2024: The aim of this study was to examine the association between in-hospital initiation of sodium glucose co-transporter 2 inhibitors (SGLT2is) and outcomes in...
: The aim of this study was to examine the association between in-hospital initiation of sodium glucose co-transporter 2 inhibitors (SGLT2is) and outcomes in hospitalized heart failure (HHF) patients utilizing data from a Greek center. : The present work was a single-center, retrospective, observational study of consecutive HF patients hospitalized in a tertiary center. The study endpoint was all-cause mortality or HF rehospitalization. Univariate and multivariate Cox proportional-hazard models were conducted to investigate the association between SGLT2i administration at discharge and the study endpoint. : Sample consisted of 171 patients, 55 of whom (32.2%) received SGLT2is at discharge. Overall, mean follow-up period was 6.1 months (SD = 4.8 months). Patients who received SGLT2is at discharge had a 43% lower probability of the study endpoint compared to those who did not receive SGLT2is at discharge (HR = 0.57; 95% CI: 0.36-0.91; = 0.018). After adjusting for age, gender, smoking, hemoglobin (Hgb), use of SGLT2is at admission, use of Angiotensin-Converting Enzyme Inhibitors (ACEI-Is)/Angiotensin Receptor Blockers (ARBs) at discharge and Sacubitril/Valsartan at discharge, the aforementioned result remained significant (HR = 0.38; 95% CI: 0.19-0.73; = 0.004). The 55 patients who received SGLT2is at discharge were propensity score matched with the 116 patients who did not receive SGLT2is at discharge. Receiving SGLT2is at discharge continued to be significantly associated with a lower probability of the study endpoint (HR= 0.43; 95% CI: 0.20-0.89; = 0.024). : Initiation of SGLT2is in HHF patients may be associated with better outcomes.
PubMed: 38930091
DOI: 10.3390/jcm13123562