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Molecules (Basel, Switzerland) Jun 2024In the field of human health research, the homeostasis of copper (Cu) is receiving increased attention due to its connection to pathological conditions, including... (Review)
Review
In the field of human health research, the homeostasis of copper (Cu) is receiving increased attention due to its connection to pathological conditions, including diabetes mellitus (DM). Recent studies have demonstrated that proteins associated with Cu homeostasis, such as ATOX1, FDX1, ATP7A, ATPB, SLC31A1, p53, and UPS, also contribute to DM. Cuproptosis, characterized by Cu homeostasis dysregulation and Cu overload, has been found to cause the oligomerization of lipoylated proteins in mitochondria, loss of iron-sulfur protein, depletion of glutathione, production of reactive oxygen species, and cell death. Further research into how cuproptosis affects DM is essential to uncover its mechanism of action and identify effective interventions. In this article, we review the molecular mechanism of Cu homeostasis and the role of cuproptosis in the pathogenesis of DM. The study of small-molecule drugs that affect these proteins offers the possibility of moving from symptomatic treatment to treating the underlying causes of DM.
Topics: Humans; Diabetes Mellitus; Copper; Homeostasis; Drug Design; Animals; Small Molecule Libraries; Mitochondria; Reactive Oxygen Species
PubMed: 38930917
DOI: 10.3390/molecules29122852 -
Molecules (Basel, Switzerland) Jun 2024Turmeric () contains curcumin, demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC). Nevertheless, curcumin is the most researched active ingredient for its numerous...
Turmeric () contains curcumin, demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC). Nevertheless, curcumin is the most researched active ingredient for its numerous pharmacological effects. We investigated the impact of these curcuminoids found in Ryudai gold, an approved cultivar of , on wound healing, inflammation, and diabetes. Sub-planter injections of carrageenan induced acute paw inflammation in rats. The wound-healing ability of 1% curcuminoids was examined by making a 6 mm round wound on the shaved dorsum of the mice with a biopsy punch. A single intraperitoneal injection of streptozotocin (50 mg/kg) was used to induce diabetes in mice. Curcuminoids at a dose rate of 100 mg/kg body weight were used with feed and as a gastric gavage to treat diabetes and inflammation in experimental animals. Paw thickness was measured at 1, 3, and 6 h following carrageenan injection. After three hours, mean paw volume was 58% in carrageenan-injected mice, which was 35%, 37%, and 31% in the curcumin, DMC, and BDMC groups, respectively. Histopathology of the paw tissue demonstrated severe infiltration of inflammatory cells and thickening of the dermis, which were remarkably improved by the curcuminoids. The wound-healing abilities were significantly higher in the curcumin- (95.0%), DMC- (93.17%), and BDMC-treated (89.0%) groups, in comparison to that of the control (65.09%) group at day nine. There were no significant differences in wound-healing activity among the groups treated with 1% curcuminoids throughout the study. Streptozotocin-induced diabetes was characterized by an increased blood glucose (552.2 mg/dL) and decreased body weight (31.2 g), compared to that of the control rats (145.6 mg/dL and 46.8 g blood glucose and body weight, respectively). It also caused an increase in serum alanine aminotransferase (ALT; 44.2 U/L) and aspartate aminotransferase (AST; 55.8 U/L) compared to that of the control group (18.6 U/L and 20.1 U/L, respectively). Histopathological examination of the liver showed that diabetes caused hepatic cellular necrosis, congestion of the central vein, and parenchymatous degeneration. However, all three curcuminoids significantly decreased blood glucose levels, ALT, and AST and improved the histopathological score of the liver. These results evidenced that not only curcumin but also DMC and BDMC have potent anti-inflammatory, wound healing, and anti-diabetic efficacy, and the Ryudai gold variety of turmeric could be used as a functional food supplement.
Topics: Animals; Curcuma; Wound Healing; Mice; Rats; Diabetes Mellitus, Experimental; Anti-Inflammatory Agents; Hypoglycemic Agents; Curcumin; Male; Plant Extracts; Carrageenan; Inflammation; Diarylheptanoids
PubMed: 38930859
DOI: 10.3390/molecules29122795 -
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 -
Molecules (Basel, Switzerland) Jun 2024Currently, an estimated 537 million individuals are affected by type 2 diabetes mellitus (T2DM), the occurrence of which is invariably associated with complications.... (Review)
Review
Currently, an estimated 537 million individuals are affected by type 2 diabetes mellitus (T2DM), the occurrence of which is invariably associated with complications. Glucose-lowering therapy remains the main treatment for alleviating T2DM. However, conventional antidiabetic agents are fraught with numerous adverse effects, notably elevations in blood pressure and lipid levels. Recently, the use of traditional Chinese medicines (TCMs) and their constituents has emerged as a preferred management strategy aimed at curtailing the progression of diabetes and its associated complications with fewer adverse effects. Increasing evidence indicates that gut microbiome disturbances are involved in the development of T2DM and its complications. This regulation depends on various metabolites produced by gut microbes and their interactions with host organs. TCMs' interventions have demonstrated the ability to modulate the intestinal bacterial microbiota, thereby restoring host homeostasis and ameliorating metabolic disorders. This review delves into the alterations in the gut microbiota and metabolites in T2DM patients and how TCMs treatment regulates the gut microbiota, facilitating the management of T2DM and its complications. Additionally, we also discuss prospective avenues for research on natural products to advance diabetes therapy.
Topics: Humans; Diabetes Mellitus, Type 2; Gastrointestinal Microbiome; Medicine, Chinese Traditional; Drugs, Chinese Herbal; Hypoglycemic Agents; Animals
PubMed: 38930814
DOI: 10.3390/molecules29122747 -
Journal of Clinical Medicine Jun 2024Chronic kidney disease (CKD) elevates the risk of cardiovascular disease (CVD) and mortality. Uremic cardiomyopathy, frequently observed in CKD and end-stage renal...
Chronic kidney disease (CKD) elevates the risk of cardiovascular disease (CVD) and mortality. Uremic cardiomyopathy, frequently observed in CKD and end-stage renal disease (ESRD), involves alterations in cardiac structure and function, which may reverse post-kidney transplantation, although data remain controversial. This study examines the relationship between graft function and changes in cardiac parameters pre- and post-transplantation in kidney transplant recipients. A total of 145 pediatric and adult recipients of living or deceased donor kidney transplants were enrolled at Gazi Yaşargil Training and Research Hospital. This cohort study utilized transthoracic echocardiographic (TTE) imaging pre-transplant and at least two years post-transplant. Echocardiographic parameters were analyzed using standard techniques. The mean age of the participants was 35 years, with 60% male. The average dialysis duration prior to transplantation was 27 months. Most recipients (83.4%) received kidneys from living donors. Left ventricular diastolic dysfunction increased significantly post-transplant ( < 0.05), while other cardiac dimensions and functions, such as ejection fraction and pulmonary artery pressure, showed no significant change ( > 0.05). Notably, diastolic dysfunction worsened in patients with dysfunctional grafts (GFR < 45), correlating with increased pulmonary artery pressure post-transplant. The rate of antihypertensive drug use and the prevalence of diabetes mellitus increased significantly post-transplant ( < 0.05). This study demonstrates that left ventricular diastolic dysfunction present before kidney transplantation continues to persist post-transplantation in patients with end-stage renal disease undergoing chronic kidney disease treatment. Furthermore, it shows an increased rate of pulmonary artery pressure and pericardial effusion in patients with dysfunctional grafts after transplantation. Further research is required to explore strategies to reverse uremic cardiomyopathy and reduce cardiovascular risk in these patients.
PubMed: 38930157
DOI: 10.3390/jcm13123629 -
Journal of Clinical Medicine Jun 2024Cardiovascular diseases (CVD) are the main cause of death in the population with diabetes mellitus. This study purposed to determine clinical laboratory markers that...
Cardiovascular diseases (CVD) are the main cause of death in the population with diabetes mellitus. This study purposed to determine clinical laboratory markers that might be correlated with the risk of CVD in individuals with type 2 diabetes mellitus (T2DM). Using data from the Clinical Center of the University of Debrecen from 2016 to 2020, we assessed cardiovascular risk in 5593 individuals with T2DM over a five-year follow-up period. There were 347 new cases of acute myocardial infarction (AMI) and stroke during the period. Following the stratification of these individuals into two groups according to the diagnosis of these CVDs until 2020, the risk of these CVDs was assessed through the utilization of the Chi-square test and Cox proportional hazards regression. The findings of the Cox proportional hazards regression model showed that the number of HbA1C measurements per year (HR = 0.46, 95% CI 0.31-0.7), decreased levels of estimated glomerular filtration rate (eGFR) (HR = 1.6, 95% CI 1.04-2.47), and elevated triglyceride levels (HR = 1.56, 95% CI 1.06-2.29) were correlated with CVD in patients with T2DM. The area under the curve (AUC) was increased from 0.557 (95% CI 0.531-0.582) to 0.628 (95% CI 0.584-0.671) after the inclusion of the laboratory variables into the model showing improved discrimination for AMI and stroke. These findings indicated that eGFR, triglyceride, and the number of HbA1C per year are correlated with AMI and stroke in patients with T2DM.
PubMed: 38930090
DOI: 10.3390/jcm13123561 -
Journal of Clinical Medicine Jun 2024: Severe aortic stenosis (AS) is the most frequent valvular heart disease. Models for stratifying cardiac damage associated with aortic stenosis have been developed to...
: Severe aortic stenosis (AS) is the most frequent valvular heart disease. Models for stratifying cardiac damage associated with aortic stenosis have been developed to predict outcomes following valve replacement. However, evidence regarding morphological and functional evolution, as well as potential changes in the degree of cardiac damage, is limited. We aim to provide information on the evolution of cardiac morphology and the function of patients undergoing transcatheter aortic valve replacement (TAVR) who have been classified using a cardiac damage staging system. : In total, 496 patients were included in the analysis, and were classified into four stages based on the extent of cardiac damage as follows: Stage 0, no cardiac damage: left ventricle global longitudinal strain (LV-GLS) < -17%; right ventricular-arterial coupling (RVAc) ≥ 0.35), and absence of significant mitral regurgitation (MR). Stage 1, left-sided subclinical damage: LV-GLS ≥ -17%. Stage 2, left-sided damage: significant MR. Stage 3, right-sided damage: RVAc < 0.35. : The mean age was 82.1 ± 5.9 years, and 53.0% were female. In total, 24.5% of patients met the criteria for Stage 0, and Stage 1 included 42.8% of patients, Stage 2 included 16.5%, and Stage 3 comprised 16.2% of patients. Mortality was 8.4% for stage 0, 17.4% for stage 1, 25.6% for stage 2, and 28.6% for stage 3 patients ( = 0.004). Diabetes mellitus (DM) ( = 0.047) and chronic kidney disease (CKD) ( = 0.024) were the only clinical predictors of no change or worsening in the stage of cardiac damage. Regarding echocardiographic variables, concomitant tricuspid, and mitral regurgitation, ≥ 2 were both significantly associated with no change or worsening, also ( < 0.001). : Cardiac damage that is secondary to severe aortic stenosis has morphological and functional repercussions that, even after valve replacement, persist and might worsen the prognosis.
PubMed: 38930068
DOI: 10.3390/jcm13123539 -
Journal of Clinical Medicine Jun 2024The association between anti-Ro/SSA antibodies and the appearance of cardiac rhythm disorders in adults is discussed. We aim to study this relationship, together with...
The association between anti-Ro/SSA antibodies and the appearance of cardiac rhythm disorders in adults is discussed. We aim to study this relationship, together with active treatments and comorbidities, and its impact on daily clinical practice in adults with systemic autoimmune diseases (SADs). This cross-sectional single-center study was conducted in a tertiary hospital between January 2021 and March 2022. A sample of adult patients followed up in the SAD Unit with a diagnosis of a SAD and previously tested for anti-Ro/SSA and anti-La/SSB were recruited. All of them underwent a 12-lead electrocardiogram. 167 patients were included. 90 (53.9%) were positive for anti-Ro60, 101 (60.5%) for anti-Ro52, and 45 (26.9%) for anti-La/SSB; 52 (31.3%) were triple-negative. 84% were women, and the mean age was 59 years (standard deviation 12.8). The most common SAD was primary Sjögren's syndrome (34.8%), followed by systemic lupus erythematosus (24.6%) and rheumatoid arthritis (22.8%). A statistically significant relationship was found between anti-Ro52 positivity and cardiac rhythm disorders (relative risk = 2.007 [1.197-3.366]), specifically QTc prolongation (relative risk = 4.248 [1.553-11.615]). Multivariate regressions showed a significant association, with diabetes mellitus being the most related comorbidity. The association between anti-Ro52 antibodies and atrioventricular conduction disorders was not significant. The presence of anti-Ro52 antibodies in adult patients with SADs is associated with an increased risk of QTc prolongation. Electrocardiographic screening of patients with SAD, anti-Ro52 antibodies, and other risk factors, like diabetes mellitus or QT-prolonging drugs, seems advisable. Those with baseline electrocardiogram abnormalities or additional risk factors should undergo electrocardiographic monitoring.
PubMed: 38930039
DOI: 10.3390/jcm13123510 -
Journal of Clinical Medicine Jun 2024Diabetes is a rapidly growing global morbidity issue with high prevalence, and the associated dysglycemia leads to complications. Patients with type 2 diabetes mellitus...
Benefits of Quercetin on Glycated Hemoglobin, Blood Pressure, PiKo-6 Readings, Night-Time Sleep, Anxiety, and Quality of Life in Patients with Type 2 Diabetes Mellitus: A Randomized Controlled Trial.
Diabetes is a rapidly growing global morbidity issue with high prevalence, and the associated dysglycemia leads to complications. Patients with type 2 diabetes mellitus (T2DM) often experience elevated anxiety levels, affecting their quality of life and diabetes management. This study investigated quercetin, a nutraceutical and potential senolytic with antioxidant activity, to detect its possible positive effect on the bio-clinical measurements and routine health of patients with T2DM. This prospective randomized controlled trial (RCT) investigated the clinical usefulness of quercetin in patients with T2DM receiving non-insulin medications. One hundred participants were stratified by age and sex (1:1) and randomized to control (n = 50) or intervention (n = 50) groups. The control received standard care only, while the intervention received 500 mg quercetin daily for 12 weeks, followed by an 8-week washout and a final consecutive 12-week supplementation period (total: 32 weeks), as adjunct to their usual care. Comprehensive health assessments, including blood analyses, were conducted at baseline and study termination. Quality of life and anxiety were assessed using the 36-item Short Form Health Survey (SF-36) and Short Anxiety Screening Test (SAST-10). Eighty-eight patients with T2DM concluded the trial. Compared with the control, glycated hemoglobin (HbA1c) levels showed a significant decrease (Δ%-change: -4.0% vs. 0.1%, = 0.011). Quercetin also significantly improved PiKo-6 readings (FEV: 5.6% vs. -1.5%, = 0.002), systolic blood pressure (-5.0% vs. -0.2%, = 0.029), night-time sleep (11.6% vs. -7.3%, < 0.001), anxiety levels (SAST-10) (-26.2% vs. 3.3%, < 0.001), and quality of life (SF-36) (both physical and mental components, < 0.001). Based on the current open-label study, quercetin appears to be a promising supplement for T2DM, providing lifestyle and care support. Further research is warranted to shift this potential from clinical usefulness and feasibility to multidisciplinary evidence.
PubMed: 38930033
DOI: 10.3390/jcm13123504 -
Journal of Clinical Medicine Jun 2024This study is a Narrative Review that aims at investigating the implications of obesity, excessive gestational weight gain (GWG) and gestational diabetes mellitus... (Review)
Review
Gestational Metabolic Risk: A Narrative Review of Pregnancy-Related Complications and of the Effectiveness of Dietary, Exercise and Lifestyle Interventions during Pregnancy on Reducing Gestational Weight Gain and Preventing Gestational Diabetes Mellitus.
This study is a Narrative Review that aims at investigating the implications of obesity, excessive gestational weight gain (GWG) and gestational diabetes mellitus (GDM). Additionally, this Review seeks to explore the effectiveness of nutrition, and/or exercise interventions during pregnancy on reducing GWG and preventing GDM. The search in literature included studies that identified obesity, GWG, GDM and associated risks during pregnancy. Also, SR and MA focusing on interventions including diet, or physical activity (PA), or combined (i.e., lifestyle interventions) and their impact on metabolic risk during pregnancy, were identified through searches in PubMed, Cochrane Database of Systematic Reviews (CDSRs), and Scopus. The study findings suggest that lifestyle interventions during pregnancy may be effective in reducing excessive GWG. Regarding the prevention of GDM, results from studies evaluating lifestyle interventions vary. However, significant and less controversial results were reported from studies assessing the efficacy of exercise interventions, particularly in high-risk pregnant women. Lifestyle interventions during pregnancy may reduce excessive GWG. Exercise during pregnancy may prevent GDM, especially in high-risk pregnant women. Future research is warranted to tailor lifestyle interventions for optimal effectiveness during pregnancy.
PubMed: 38929991
DOI: 10.3390/jcm13123462