Cardiovascular Protection Research Articles

Design considerations for future renoprotection trials in the era of multiple therapies for chronic kidney disease.

Nephrology has benefited from conducting increasingly large high-quality trials in the last 5-10 years. In addition to the long-standing known benefits of renin-angiotensin system inhibitors, we now have multiple pharmacotherapies that provide kidney and/or cardiovascular protection for certain types of patient with chronic kidney disease (CKD). These include sodium-glucose co-transporter 2 inhibitors (SGLT2i), a non-steroidal mineralocorticoid receptor antagonist and a glucagon-like peptide-1 receptor agonist. Trials of SGLT2i have had particularly important impact, as wide eligibility criteria in pivotal trials have enabled safety and efficacy across a wide range of causes of CKD to be demonstrated. These findings support the concept of final common pathways of CKD progression and should encourage similar trial designs recruiting broad ranges of patients at risk of CKD progression. This is important as these new drugs do not completely arrest CKD progression nor do they mitigate the full excess of cardiovascular disease. In the current era of multiple therapies to manage risk of CKD progression, trial design and conduct also need to consider new challenges. These include falling event rates, establishing standard of care for participants pre-randomization and improving the inclusion of trial participants understudied in previous trials. Streamlining trial design and conduct and reducing participation burden for patients and clinicians is increasingly important to facilitate larger sample sizes and to optimize adherence to study interventions and follow-up. Potential other solutions include maintaining a focus on wide generalizability (to include understudied patient groups) and empowering patients to volunteer for trials (through public and patient involvement and large-scale invitation methods), as well as innovations in trial design (including use of pre-randomization run-in periods to implement standard of care and factorial or platform trials to assess multiple treatments simultaneously).

Endothelial-Protective Actions of Diethylether Extract from Gentiana kochiana and Xanthone Gentiacaulein Against Oxidized LDL-Induced Injury—In Vitro Evaluation

Endothelial dysfunction is an early pathophysiological event in atherosclerosis. The endothelial-protective abilities of diethylether extract (EE) from the Gentiana kochiana (Gentianaceae) herb and its main component, xanthone aglycone gentiacaulein (GC), were evaluated in an oxidized low-density lipoprotein (oxLDL)-treated EA.hy926 endothelial cell line. The EE and GC actions were assessed using cell viability assays, flow cytometry, immunoblot, DPPH, NBT, TBARS, conjugated diene formation, and Griess tests. Both EE and GC prevented oxLDL-induced apoptosis by reducing intracellular reactive oxygen species levels, mitochondrial depolarization, and caspase activation in EA.hy926 cells. EE and GC dose-dependently diminished oxLDL-induced cellular lipid peroxidation. In cell-free conditions, EE moderately scavenged superoxide anions and had no affinity toward DPPH radicals, GC did not interact with either of investigated free radicals, while both EE and GC effectively delayed Cu²⁺-induced LDL oxidation. EE and GC upregulated oxLDL-suppressed protective Akt/CREB/eNOS and ERK signals and restored oxLDL-reduced nitric oxide levels. Therefore, EE and GC effectively counteract oxLDL-induced endothelial apoptosis by reducing oxidative stress, promoting mitochondrial recovery, and enhancing the prosurvival Akt/CREB/eNOS axis and ERK activity. Our study is the first to demonstrate that xanthone-rich EE from aerial parts of G. kochiana and xanthone GC alleviate oxLDL-induced endothelial cell injury, underscoring their potential for cardiovascular protection.

The hidden interplay between sex and adverse outcomes in incident dialysis patients: the role of aortic calcification

Abstract Background Research on the sex disparity in the prognosis of chronic kidney disease (CKD), particularly among those who are newly initiating dialysis, is limited and inconclusive. This study aimed to investigate the associations between sex and all-cause mortality and major cardiovascular adverse events (MACE), with a particular focus on the presence of aortic calcification (AC). Methods We conducted a post hoc analysis of 1459 incident dialysis patients included in this prospective cohort study. The primary outcome of interest was all-cause mortality, and the secondary endpoint was a composite of MACE. Results During a median follow-up period of 3.55 years, 362 (269 male and 93 female) patients died and 477 (342 male and 135 female) patients developed MACE. The risks for all-cause mortality (HR 0.61, 95% CI 0.47-0.79) and MACE (HR 0.74, 95% CI 0.60-0.93) were lower in females than in males. This finding was robust across multiple sensitivity analyses and most subgroups. Moreover, the associations between sex and adverse outcomes were significantly modified by AC status at dialysis initiation (p for interaction < 0.05). Specifically, among patients without AC, females exhibited lower risks for all-cause mortality (HR 0.45, 95% CI 0.29-0.69; p < 0.001) and MACE (HR 0.67, 95% CI 0.49-0.93; p=0.015),whereas no differences were observed for all-cause mortality (HR 0.82; 95% CI 0.59-1.15; p=0.256) or MACE (HR 0.80, 95% CI 0.59-1.10; p=0.174) among patients with AC. Conclusions In patients with renal failure receiving dialysis, AC abolished the survival and cardiovascular protection observed in female versus male patients. This finding supports the need for greater awareness of the AC burden in female dialysis patients.

Exploring the therapeutic potential of lupeol: A review of its mechanisms, clinical applications, and advances in bioavailability enhancement.

Lupeol, a naturally occurring triterpenoid, has garnered significant attention for its diverse range of biological activities and potential therapeutic applications. This comprehensive review delves into the various aspects of lupeol, including its sources, extraction methods, chemical characteristics, pharmacokinetics, safety evaluation, mechanisms of action, and applications in disease treatment. We highlight the compound's unique carbon skeleton and its role in inflammation regulation, antioxidant activity, and broad-spectrum antimicrobial effects. The review also underscores lupeol's potential in cancer therapy, cardiovascular protection, metabolic disease management, and wound healing. Furthermore, we discuss the challenges and future perspectives of lupeol's clinical application, emphasizing the need for further research to improve its bioavailability and explore its full therapeutic potential. The review concludes by recognizing the significance of lupeol in drug development and healthcare, with expectations for future breakthroughs in medical applications.

Explainable Machine Learning Algorithms to Predict Cardiovascular Strokes

Cardiovascular disease has been more common throughout the past several decades. Cardiovascular disease detection methods use machine learning algorithms to assess data and provide accurate cardiac diagnosis. An accurate and comprehensive assessment of cardiovascular risk is essential to improve cardiovascular protection and reduce the frequency and severity of heart attacks and strokes. This paper proposes a machine learning-based autonomous strategy for the diagnosis of cardiovascular disease. Some preprocessing methods were applied to improve the results and accuracy. Finally, lazy prediction was used to find the best model by applying a neural network and two ensemble models. The best accuracy of 99% was obtained with the HistGradientBoosting (ensemble) classifier, which obtained respectable results with a higher accuracy rate. This model can enhance the ability to predict cardiovascular disease with better accuracy.

Preparation methods, structural features, biological activities and potential applications of Ophiopogon japonicus polysaccharides: An updated review.

Ophiopogon japonicus (O. japonicus) has a history of thousands of years as herbal medicine and nutritional food in China. Polysaccharides are one of the main bioactive components of O. japonicus. Various extraction methods and purification techniques have been employed to obtain O. japonicus polysaccharides (OJPs). Nevertheless, the structural characteristics of OJPs remain incompletely understood and require further investigation through the integration of advanced analytical techniques to uncover potential structure-activity relationships. Moreover, OJPs exhibit a variety of biological activities, such as regulating gut microbiota, providing cardiovascular protection, lowering blood glucose, and combating obesity. These diverse pharmacological effects make OJPs highly promising for widespread application in industries such as pharmaceuticals and food. Therefore, this review aims to provide a comprehensive overview of OJPs, covering their preparation methods, structural features, bioactivity, and structure-activity relationships. Here also emphasizes the significant promise of medicine and functional foods fields and advocating for their integration into clinical and industrial processes.

Does the Mechanism of Weight Loss Matter for Cardiovascular Protection?

Does the Mechanism of Weight Loss Matter for Cardiovascular Protection?

Euodiae Fructus: a review of botany, application, processing, phytochemistry, quality control, pharmacology, and toxicology

Euodiae Fructus (EF) is the dried and nearly ripe fruit of Euodia rutaecarpa, first recorded in Shen Nong’s Herbal Classic. EF is a versatile Traditional Chinese Medicine (TCM) known for the effects of dispelling colds and alleviating pain, suppressing adverse qi to relieve vomiting, and boosting yang to mitigate diarrhea. However, it should be noted that EF possesses mild toxicity. In TCM prescriptions, EF is employed to treat various ailments, including abdominal pain, diarrhea, chronic non-atrophic gastritis, irritable bowel syndrome, and primary dysmenorrhea. This review collected the literature published before September 2024 on EF. An exhaustive analysis of EF literature was conducted utilizing multiple sources, namely classic TCM books and various scientific databases like Web of Science, PubMed, Elsevier, ACS, ResearchGate, Google Scholar, and Chinese National Knowledge Infrastructure. So far, more than 300 metabolites have been extracted and identified from EF, exhibiting various pharmacological effects, such as cardiovascular protection, gastrointestinal protection, neuroprotection, anti-inflammation, analgesia, anti-tumor, glucose and lipid metabolism regulation, etc. It also exhibits diverse toxicological properties and poses specific toxic risks to the liver, heart, and kidney. Nonetheless, research is scarce regarding the toxicology of EF, especially on its cardiotoxicity and nephrotoxicity. Further in-depth research is necessary to explore the mechanisms underlying EF’s pharmacological and toxicological mechanisms and to develop strategies for quality control and toxicity mitigation. The toxicity of EF can be reduced by processing, but this aspect is rarely discussed, and the quality control needs to be further standardized. Evodiamine, rutaecarpine, and limonin are the effective metabolites of EF and are also one of the causes of EF toxicity. The pharmacological effects of evodiamine and rutaecarpine have been intensely studied, but there are few studies on limonin and other metabolites of EF. Therefore, this paper focuses on the botanical characteristics, traditional applications, processing methods, phytochemistry, quality control, pharmacology, and toxicology of EF. We hope this paper provides a theoretical basis for the future high-value and high-connotation development of EF.

Shenmai injection revives cardiac function in rats with hypertensive heart failure: involvement of microbial-host co-metabolism

Heart failure (HF) is a complex syndrome marked by considerable expenditures and elevated mortality and morbidity rates globally. Shenmai injection (SMI), a form of Traditional Chinese Medicine-based therapy, has demonstrated effectiveness in treating HF. Recent research suggests that Traditional Chinese Medicine (TCM) may induce beneficial changes in microbial-host co-metabolism, potentially providing cardiovascular protection. This study used a rat model of hypertensive heart failure (H-HF) to explore the mechanism of SMI. The possible compounds and key targets of SMI against H-HF were investigated using network pharmacology. The pharmacodynamics of SMI were validated using the H-HF animal model, with analysis of fecal gut microbiota integrating metabolomics and 16S rRNA sequencing. Metorigin metabolite traceability analysis and the MetaboAnalyst platform were utilized to explore the action mechanism. To evaluate changes in serum TMAO levels, targeted metabolomics was performed. Finally, the study looked at the intrinsic relationships among modifications in the intestinal flora, metabolite profile changes, and the targets of SMI compounds to clarify how they might be used to treat H-HF. According to metabolomics and 16S rRNA sequencing, by reestablishing homeostasis in the gut microbiota, SMI affects vital metabolic pathways, such as energy metabolism, amino acid metabolism, and bile acid metabolism. Increased serum TMAO levels were identified to be a risk factor for H-HF, and SMI was able to downregulate the levels of TMAO-related metabolites. Network pharmacology analysis identified 13 active components of SMI targeting 46 proteins, resulting in differential expression changes in 8 metabolites and 24 gut microbes. In conclusion, this study highlights the effectiveness of SMI in alleviating H-HF and its potential to modulate microbial-host co-metabolism. Through a comprehensive discussion of the interconnected relationships among the components, targets, metabolites, and gut microbiota, it provided fresh light on the therapeutic mechanism of SMI on H-HF.

Sodium-Glucose Cotransporter-2 Inhibitors in Diabetic Kidney Disease and Beyond

Background Sodium-glucose co-transporter 2 inhibitors (SGLT2is) have significantly impacted the management of diabetic kidney disease (DKD) and heart failure (HF), providing benefits beyond glycemic control. This review examines the mechanisms through which SGLT2is provide renal and cardiovascular protection and assesses their clinical efficacy. Summary By inducing glucosuria and natriuresis, SGLT2is alleviate multiple complications induced by chronic hyperglycemia. Moreover, SGLT2is reduce albuminuria, improve tubular function, and modulate erythropoiesis. Additionally, they mitigate inflammation and fibrosis by decreasing oxidative stress and downregulating pro-inflammatory pathways. Clinical trials have demonstrated significant reductions in renal and cardiovascular events among patients with type 2 diabetes mellitus. A comprehensive review of the literature was conducted through PUBMED, highlighting the effects of SGLT2is and the results of major clinical trials involving SGLT2is. Key messages SGLT2is play a crucial role in the management of DKD and HF by addressing multiple pathogenic pathways. Currently, SGLT2is are included in clinical guidelines for DKD and HF management, and their benefits extend to non-diabetic populations. Further research is needed to explore SGLT2is’ multifaceted mechanisms and potential applications across diverse patient populations and different disease etiologies.

Harnessing Therapeutic Potential of Allicin Against Cancer: An Exploratory Review.

The biological name of garlic is Allium sativum L., a familiar spice with various health benefits. These benefits are mainly attributable to the compound diversity of garlic, which includes saponins, polysaccharides, organic sulfides, and phenolic compounds. Allicin exhibits therapeutic activity such as antibacterial, anticancer, anti-inflammatory, immunomodulatory, anti-diabetic, and cardiovascular protection. This present study explores the anticancer potential of allicin, including cell line studies that examine its effects on various cancer types by analyzing the growth inhibition of cancer cells at different allicin concentrations. This study aims to present a concise overview of allicin, update patent statistics, and provide detailed insights into its wide range of therapeutic benefits, with a particular emphasis on its anticancer properties. A literature review has been conducted using reliable sources, including ClinicalTrials.gov, ScienceDirect, PubMed, Scopus, and other reputable foundations, to assess the true potential of allicin in cancer therapeutics. Allicin, a naturally occurring compound in garlic, represents a promising treatme nt approach for cancer due to its potent anticancer properties. Cell line studies have shown that various concentrations of allicin significantly inhibit cancer cell growth, underscoring its effectiveness against cancer types such as breast, pancreatic, liver, renal, osteosarcoma, gastric, colorectal, and stomach cancers. By effectively targeting cancer cells, allicin stands out as a potential therapeutic agent. The primary goal of the review is to highlight the anticancer potential of allicin, along with an overview of clinical and patent studies.

Effectiveness and Safety of Ticagrelor Monotherapy After Short-Duration Dual Antiplatelet Therapy in PCI Patients: A Systematic Review and Meta-Analysis.

Dual antiplatelet therapy (DAPT), consisting of aspirin and a P2Y12 inhibitor, is the standard treatment for patients undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES). However, the optimal duration of DAPT remains debated due to the need to balance ischemic event reduction with bleeding risks. This study evaluates the efficacy and safety of ticagrelor monotherapy after short-duration DAPT (1-3 months) compared to extended DAPT, focusing on major bleeding and cardiovascular outcomes. A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines. Randomized controlled trials (RCTs) comparing ticagrelor monotherapy after short-duration DAPT to extended DAPT were identified from PubMed, Embase, and the Cochrane Library. Data on major bleeding, major adverse cardiovascular and cerebrovascular events (MACCE), myocardial infarction, stroke, stent thrombosis, and mortality were analyzed, and risk ratios (RR) with 95% confidence intervals (CI) were calculated using a random-effects model. Five RCTs involving 32,393 patients were included. Ticagrelor monotherapy significantly reduced MACCE (RR: 0.88; 95% CI: 0.77-0.99; p=0.04) and major bleeding (RR: 0.53; 95% CI: 0.37-0.77; p=0.0008) compared to extended DAPT. It also significantly reduced all-cause mortality (RR: 0.82; 95% CI: 0.67-0.99; p=0.04) and cardiovascular death (RR: 0.68; 95% CI: 0.49-0.94; p=0.02). The incidence of myocardial infarction, stent thrombosis, and stroke were similar between the groups. Net adverse clinical events (NACE) were 27% lower with ticagrelor monotherapy (RR: 0.73; 95% CI: 0.63-0.85; p<0.0001). In conclusion, ticagrelor monotherapy after short-duration DAPT reduces major bleeding complications without compromising cardiovascular protection. This approach offers a promising strategy to optimize outcomes for PCI patients, particularly those at high bleeding risk. Further studies are needed to refine the optimal DAPT duration in various patient populations, especially those with higher ischemic risk.

Therapeutic Potential of GLP-1 Receptor Agonists in Diabetes and Cardiovascular Disease: Mechanisms and Clinical Implications.

Glucagon-like peptide-1 (GLP-1) is a crucial incretin hormone secreted by intestinal endocrine L cells. Given its pivotal physiological role, researchers have developed GLP-1 receptor agonists (GLP-1 RAs) through structural modifications. These analogues display pharmacological effects similar to those of GLP-1 but with augmented stability and are regarded as an effective means of regulating blood glucose levels in clinical practice. This review aims to comprehensively summarize the role of GLP-1 RAs in the management of diabetes mellitus (DM) and cardiovascular disease (CVD), with a particular emphasis on the underlying signal transduction pathways and their therapeutic potential. A comprehensive review was carried out through literature research. In pancreatic β-cells, GLP-1 RAs regulate the secretion of insulin and glucagon in a glucosedependent manner by influencing signaling pathways such as cAMP, PI3K, and MAPK. They also contribute to the regulation of blood glucose levels by promoting the proliferation of β-cells and inhibiting apoptosis in these cells. Recent comprehensive studies have also demonstrated the favorable impact of GLP-1 RAs on cardiovascular wellbeing. In addition to the cardiovascular protection afforded by glucose metabolism regulation, a large body of evidence from animal and cellular studies has corroborated the beneficial effects of GLP-1 RAs on conditions such as heart failure (HF), hypertension, and ischemic cardiomyopathy. These benefits are mainly attributed to the alleviation of inflammatory responses, reduction of oxidative stress, and prevention of cell apoptosis. Clinical data shows that GLP-1 RAs can reduce the risk of major adverse cardiovascular events (MACE) in diabetic patients. GLP-1 RAs play an important role in the management of both diabetes and cardiovascular diseases. They show potential therapeutic value through the modulation of multiple signal transduction pathways. However, there may still be some issues in practical applications that require further research and resolution.

Clopidogrel combined with rivaroxaban in peripheral artery disease after revascularization.

To evaluate the efficacy and safety of clopidogrel-rivaroxaban combination compared to aspirin-rivaroxaban combination in patients with symptomatic peripheral artery disease (PAD). Consecutive patients with symptomatic PAD patients were analyzed from January, 2018 to June, 2022at Nanjing Drum Tower Hospital. Patients were divided into two groups based on the antithrombotic therapy. The primary efficacy outcome was a composite of major adverse cardiovascular events (MACE) and major adverse limb events (MALE), and the primary safety outcome was major bleeding. Patients were followed until the first occurrence of any outcomes or the study end date (30 June 2024). A total of 695 patients were enrolled into this study. The clopidogrel-rivaroxaban combination significantly reduced the risk of composite outcome (HR: 0.59, 95%CI: 0.41-0.83) without increasing the risk of major bleeding (HR: 0.68, 95%CI: 0.27-1.69). When analyzed separately, clopidogrel-rivaroxaban combination was associated with a reduced risk of MALE (HR: 0.61, 95%CI: 0.41-0.91), although no significant differences were observed in terms of MACE (HR: 0.64, 95%CI: 0.34-1.20) or all bleeding events (HR: 1.00, 95%CI: 0.52-1.93). In the subgroup analysis, there were no significant interactions between the treatment groups and the subgroups of age, diabetes, lesion sites, Rutherford classifications and renal function for composite outcome, MACE and MALE. The clopidogrel-rivaroxaban combination in PAD patients may offer enhanced cardiovascular protection without increasing the risk of bleeding complications. These findings suggested that clopidogrel could be a superior alternative to aspirin in dual antithrombotic therapy for PAD management.

Potential beneficial impacts of tadalafil on cardiovascular diseases.

Tadalafil is a selective phosphodiesterase type 5 (PDE5) inhibitor commonly used for the treatment of erectile dysfunction and benign prostatic hyperplasia. Its mechanism of action involves the inhibition of PDE5, leading to increased levels of nitric oxide and cyclic guanosine monophosphate in the corpus cavernosum, which facilitates smooth muscle relaxation. This article reviews studies using tadalafil in the treatment of cardiovascular diseases and emphasizes its potential advantages in conditions such as pulmonary arterial hypertension, atherosclerosis, coronary artery disease, myocardial infarction, heart failure, stroke, diabetic ulcers, and cardiomyopathy. Although tadalafil shows potential efficacy in treating cardiovascular disease, further experimental studies are needed to clarify its pharmacological effects on cardiovascular protection beyond PDE5 inhibition.

Coronary atherosclerosis in athletes: emerging concepts and preventive strategies.

There should be no assumption that an athlete is immune to coronary artery disease (CAD), even when traditional cardiovascular (CV) risk factors appear well-managed. Excelling in certain aspects of health does not equate to total CV protection. Recent data from cardiac imaging studies have raised the possibility that long-term, high-volume, high-intensity endurance exercise is associated with coronary atherosclerosis. Whilst the risk of CV events has not been shown to rise with athletic activity, the potential for CAD should not be overlooked as it is the leading cause of sudden cardiac death in athletes >35 years of age (i.e. 'Masters athletes'). Evaluating both traditional and non-traditional risk factors for CAD is the most important part of pre-participation evaluation in Masters athletes. When managing athletes at risk of CAD it is important to adopt a shared decision-making approach regarding lifestyle adaptation and lipid-lowering treatments. In the great majority of athletes, after excluding the presence of symptoms and inducible ischaemia, this advice should include encouragement to continue exercising as available data indicate that higher levels of fitness are associated with a markedly attenuated incidence of coronary events regardless of the severity of coronary disease. Future research is needed to establish the relationship between clinically relevant CAD outcomes and coronary artery calcification in Masters Athletes, the role of sex, as well as exploration of the mechanisms underpinning these unexpected CV adaptations.

Plackett-Burman Design Combined With Response Surface Methodology to Recover Polysaccharides With Cardiovascular Protective Potential From Waste Zizania Latifolia Bract.

Zizania latifolia is the second aquatic vegetable in China. The circular valorization of its waste bracts remains an ongoing concern. In this work, the cellulase-microwave-assisted extraction (CMAE) of polysaccharides from waste Z. latifolia bracts (PWZLBs) was explored. Seven parameters were selected via a single-factor test, of which three significant parameters were screened out using the Plackett-Burman design, followed by response surface methodology optimization. The optimal CMAE for PWZLBs were: cellulase addition of 0.5%, microwave time of 7min, and microwave power of 425W, resulting in a yield of 0.82 ±0.08%. Four polysaccharide fractions (PWZLBs-1 ∼ 4) were isolated from PWZLBs, of which PWZLBs-1 accounted for a major proportion and exerted higher scavenging capacities on diphenyl picrylhydrazyl and hydroxyl radicals. More importantly, PWZLBs-1 elicited anticoagulation via prolonging thrombin time and prothrombin time, exhibiting potential for cardiovascular protection. Various characterizations confirmed that PWZLBs-1 is a heteropolysaccharide containing uronic acids and sulfates, with galactose (34.3%) as the predominant monosaccharide, and has a molecular weight of 8061kDa. This work provides clues for the circular valorization of waste Z. latifolia bracts and offers potential opportunities for the development of new cardiovascular protective drugs.

The Role of SGLT-2 Inhibitors in Cardiovascular and Renal Protection

SGLT-2 inhibitors have revolutionized the management of chronic diseases, demonstrating profound cardiovascular and renal protective effects that extend beyond their original purpose of glucose-lowering in T2DM. These agents target fundamental pathophysiological mechanisms, including hemodynamic regulation, metabolic efficiency, inflammation, and oxidative stress, making them effective across diverse populations. Landmark clinical trials such as EMPA-REG OUTCOME, CANVAS, DAPA-HF, and DAPA-CKD have shown significant reductions in cardiovascular death, heart failure hospitalizations, and the progression of CKD, even in non-diabetic patients. While generally well-tolerated, SGLT-2 inhibitors require careful patient selection to mitigate risks such as euglycemic diabetic ketoacidosis and volume depletion. Their broad applicability underscores their role as a cornerstone therapy, redefining integrated care for heart failure, CKD, and related conditions. As research expands, SGLT-2 inhibitors promise to further transform chronic disease management, offering improved outcomes, quality of life, and survival for millions worldwide.

A Comprehensive Analysis of Diabetic Complications and Advances in Management Strategies

Diabetes mellitus, particularly type 2 diabetes mellitus (T2DM), is a pervasive chronic disease that affects millions of people worldwide. It predisposes individuals to a range of severe microvascular and macrovascular complications, which drastically impact the patient's quality of life and increase mortality rates owing to various comorbidities. This extensive review explores the intricate pathophysiology underlying diabetic complications, focusing on key mechanisms, such as atherosclerosis, insulin resistance, chronic inflammation, and endothelial dysfunction. It also highlights recent therapeutic advancements, including the introduction of SGLT2 inhibitors and GLP-1 receptor agonists, which provide benefits beyond glycemic control and offer cardiovascular and renal protection. Furthermore, the future position of SGLT2 inhibitors and GLP-1 receptor agonists in terms of the prevention of diabetes and macrovascular diseases will be discussed. Considering the differences in insulin secretion capacity between Western and Asian patients, including Japanese patients, we propose a treatment strategy for high-quality diabetes in Japan.

The Impact of Polyphenols on Nutrition and Health

Polyphenols are plant-sourced compounds that exhibit important dietary features on human health. They have been defined and used either as a food source or as a raw material in the food industry to enhance functional properties and nutritional quality. They have significant positive bioactivities as; antioxidant, anti-inflammatory, anti-carcinogenic, cardiovascular health protection, immune supporter, and also benefits on digestion and brain functioning. The effects and bioactivity ranges were studied in the literature which has been discussed in the review to emphasize the importance of these natural compounds to provide insight into health and well-being.