ABSTRACT
BACKGROUND: Obesity and its associated complications raise significant public concern, revealing gender disparities in the susceptibility to metabolic disorders, with females often displaying greater resistance to obesity-related metabolic disorder than males. Sestrin2 is a crucial protein involved in metabolism and energy balance. This study seeks to explore whether Sesn2 knockout (KO) exacerbates high-fat diet (HFD) induced obesity in female mice. METHODS: Female mice with wild-type (WT) and Sesn2 KO were subjected to a 12-week regimen of normal diet or HFD. Using a Body Composition Analyzer, body composition was gauged. Biochemical assays encompassed glucose, lipid, and liver function measurements, alongside 24-hour urine albumin excretion. Echocardiographic evaluation assessed cardiac function. Histopathological analysis of key metabolic tissues (liver, kidney, and heart tissues) were conducted. Western blotting or qRT-PCR evaluated key proteins and genes linked to inflammation, mitochondrial, and lipid metabolism in adipose tissues. RESULTS: In comparison to mice fed a regular diet, those on a HFD exhibited significant increases in body weight and fat mass. Notably, Sesn2 KO further aggravated obesity, showcasing the most pronounced metabolic anomalies: elevated body weight, fat mass, impaired glucose tolerance, and insulin sensitivity, alongside heightened levels of free fatty acids and triglycerides. Additionally, KO-HFD mice displayed exacerbated multi-tissue impairments, including elevated hepatic enzymes, increased urinary albumin excretion, compromised cardiac function, and accumulation of lipids in the liver, kidney, and heart. Moreover, adipose tissue showcased altered lipid dynamics and function, characterized by enhanced triglyceride breakdown and modified adipokine levels. Browning was diminished, along with decreased Pgc1α and Sirt1 in KO-HFD mice. CONCLUSION: Sesn2 KO exacerbates HFD-induced obesity and metabolic disorders in female mice. These findings underscore Sestrin2's novel role as a regulator of obesity in female mice.
ABSTRACT
BACKGROUND: Ketogenic diets are increasingly popular for addressing obesity, but their impacts on the gut microbiota and metabolome remain unclear. This paper aimed to investigate how a ketogenic diet affects intestinal microorganisms and metabolites in obesity. METHODS: Male mice were provided with one of the following dietary regimens: normal chow, high-fat diet, ketogenic diet, or high-fat diet converted to ketogenic diet. Body weight and fat mass were measured weekly using high-precision electronic balances and minispec body composition analyzers. Metagenomics and non-targeted metabolomics data were used to analyze differences in intestinal contents. RESULTS: Obese mice on the ketogenic diet exhibited notable improvements in weight and body fat. However, these were accompanied by a significant decrease in intestinal microbial diversity, as well as an increase in Firmicutes abundance and a 247% increase in the Firmicutes/Bacteroidetes ratio. The ketogenic diet also altered multiple metabolic pathways in the gut, including glucose, lipid, energy, carbohydrate, amino acid, ketone body, butanoate, and methane pathways, as well as bacterial secretion and colonization pathways. These changes were associated with increased intestinal inflammation and dysbiosis in obese mice. Furthermore, the ketogenic diet enhanced the secretion of bile and the synthesis of aminoglycoside antibiotics in obese mice, which may impair the gut microbiota and be associated with intestinal inflammation and immunity. CONCLUSIONS: The study suggest that the ketogenic diet had an unfavorable risk-benefit trade-off and may compromise metabolic homeostasis in obese mice.
Subject(s)
Diet, High-Fat , Diet, Ketogenic , Gastrointestinal Microbiome , Metagenomics , Obesity , Diet, Ketogenic/adverse effects , Animals , Male , Mice , Obesity/metabolism , Obesity/microbiology , Obesity/etiology , Diet, High-Fat/adverse effects , Metagenomics/methods , Metabolomics/methods , Dysbiosis/microbiology , Dysbiosis/metabolism , Mice, Inbred C57BL , Metabolome , Body WeightABSTRACT
The increasing incidence of chronic kidney disease (CKD) poses a significant public health concern, prompting heightened attention to its treatment. Incretins, including glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide, are intestinal peptides released after nutrient intake, known for their hypoglycemic effects in diabetes management. Recent advancements highlight the promising outcomes of GLP-1 receptor agonists in reducing CKD risk factors and improving renal outcomes. The multifaceted functions of GLP-1, such as its anti-obesity, anti-hypertensive, anti-hyperglycemic, anti-lipid, anti-inflammatory, and endothelial function protective properties, contribute to its potential as a therapeutic agent for CKD. Although experiments suggest the potential benefits of incretin in CKD, a comprehensive understanding of its specific mechanisms is still lacking. This review aims to provide a detailed examination of current evidence and potential future directions, emphasizing the promising yet evolving landscape of incretin agonists in the context of CKD.
Subject(s)
Glucagon-Like Peptide 1 , Glucagon-Like Peptide-1 Receptor , Incretins , Renal Insufficiency, Chronic , Humans , Renal Insufficiency, Chronic/drug therapy , Renal Insufficiency, Chronic/metabolism , Incretins/therapeutic use , Glucagon-Like Peptide 1/agonists , Glucagon-Like Peptide 1/metabolism , Glucagon-Like Peptide-1 Receptor/agonists , Animals , Hypoglycemic Agents/therapeutic useABSTRACT
The global burden of diseases and injuries poses complex and pressing challenges. This study analyzed 369 diseases and injuries attributed to 84 risk factors globally from 1990 to 2019, projecting trends to 2040. In 2019, global risks caused 35 million deaths. Non-communicable diseases were responsible for 8.2 million deaths, primarily from air pollution (5.5 million). Cardiovascular disease from air pollution had a high age-standardized disability-adjusted life year rate (1,073.40). Communicable, maternal, neonatal, and nutritional diseases caused 1.4 million deaths, mainly due to unsafe water and sanitation. Occupational risks resulted in 184,269 transport-related deaths. Behavioral risks caused 21.6 million deaths, with dietary factors causing 6.9 million cardiovascular deaths. Diabetes linked to sugar-sweetened beverages showed significant growth (1990-2019). Metabolic risks led to 18.6 million deaths. Projections to 2040 indicated persistent challenges, emphasizing the urgent need for targeted interventions and policies to alleviate the global burden of diseases and injuries.
ABSTRACT
Cancer remains a significant challenge in the field of oncology, with the search for novel and effective treatments ongoing. Calycosin (CA), a phytoestrogen derived from traditional Chinese medicine, has garnered attention as a promising candidate. With its high targeting and low toxicity profile, CA has demonstrated medicinal potential across various diseases, including cancers, inflammation, and cardiovascular disease. Studies have revealed that CA possesses inhibitory effects against a diverse array of cancers. The underlying mechanism of action involves a reduction in tumor cell proliferation, induction of tumor cell apoptosis, and suppression of tumor cell migration and invasion. Furthermore, CA has been shown to enhance the efficacy of certain chemotherapeutic drugs, making it a potential component in treating malignant tumors. Given its high efficacy, low toxicity, and multi-targeting characteristics, CA holds considerable promise as a therapeutic agent for cancer treatment. The objective of this review is to present a synthesis of the current understanding of the antitumor mechanism of CA and its research progress.
Subject(s)
Isoflavones , Neoplasms , Phytoestrogens , Isoflavones/therapeutic use , Isoflavones/pharmacology , Humans , Phytoestrogens/therapeutic use , Phytoestrogens/pharmacology , Neoplasms/drug therapy , Cell Proliferation/drug effects , Apoptosis/drug effects , Cell Movement/drug effects , Antineoplastic Agents, Phytogenic/therapeutic use , Antineoplastic Agents, Phytogenic/pharmacologyABSTRACT
The growing global burden of cancer, especially among people aged 60 years and over, has become a key public health issue. This trend suggests the need for a deeper understanding of the various cancer types in order to develop universally effective treatments. A prospective area of research involves elucidating the interplay between the senescent microenvironment and tumor genesis. Currently, most oncology research focuses on adulthood and tends to ignore the potential role of senescent individuals on tumor progression. Senescent cells produce a senescence-associated secretory phenotype (SASP) that has a dual role in the tumor microenvironment (TME). While SASP components can remodel the TME and thus hinder tumor cell proliferation, they can also promote tumorigenesis and progression via pro-inflammatory and pro-proliferative mechanisms. To address this gap, our review seeks to investigate the influence of senescent microenvironment changes on tumor development and their potential implications for cancer therapies.
Subject(s)
Carcinogenesis , Cellular Senescence , Neoplasms , Tumor Microenvironment , Humans , Neoplasms/pathology , Neoplasms/therapy , Carcinogenesis/pathology , AnimalsABSTRACT
The global diabetes surge poses a critical public health challenge, emphasizing the need for effective glycemic control. However, rapid correction of chronic hyperglycemia can unexpectedly trigger microvascular complications, necessitating a reevaluation of the speed and intensity of glycemic correction. Theories suggest swift blood sugar reductions may cause inflammation, oxidative stress, and neurovascular changes, resulting in complications. Healthcare providers should cautiously approach aggressive glycemic control, especially in long-standing, poorly controlled diabetes. Preventing and managing these complications requires a personalized, comprehensive approach with education, monitoring, and interdisciplinary care. Diabetes management must balance short and long-term goals, prioritizing overall well-being. This editorial underscores the need for a personalized, nuanced approach, focusing on equilibrium between glycemic control and avoiding overcorrection.
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Sodium-glucose cotransporter-2 (SGLT2) inhibitors have emerged as a pivotal intervention in diabetes management, offering significant cardiovascular benefits. Empagliflozin, in particular, has demonstrated cardioprotective effects beyond its glucose-lowering action, reducing heart failure hospitalizations and improving cardiac function. Of note, the cardioprotective mechanisms appear to be inde-pendent of glucose lowering, possibly mediated through several mechanisms involving shifts in cardiac metabolism and anti-fibrotic, anti-inflammatory, and anti-oxidative pathways. This editorial summarizes the multifaceted cardiovascular advantages of SGLT2 inhibitors, highlighting the need for further research to elucidate their full therapeutic potential in cardiac care.
ABSTRACT
Heart diseases are a major cause of morbidity and mortality worldwide. Understanding the molecular mechanisms underlying these diseases is essential for the development of effective diagnostic and therapeutic strategies. The FHL family consists of five members: FHL1, FHL2, FHL3, FHL4, and FHL5/Act. These members exhibit different expression patterns in various tissues including the heart. FHL family proteins are implicated in cardiac remodeling, regulation of metabolic enzymes, and cardiac biomechanical stress perception. A large number of studies have explored the link between FHL family proteins and cardiac disease, skeletal muscle disease, and ovarian metabolism, but a comprehensive and in-depth understanding of the specific molecular mechanisms targeting FHL on cardiac disease is lacking. The aim of this review is to explore the structure and function of FHL family members, to comprehensively elucidate the mechanisms by which they regulate the heart, and to explore in depth the changes in FHL family members observed in different cardiac disorders, as well as the effects of mutations in FHL proteins on heart health.
Subject(s)
Heart Diseases , Muscular Diseases , Humans , Muscle Proteins/metabolism , Muscular Diseases/genetics , Heart Diseases/genetics , Mutation , Intracellular Signaling Peptides and Proteins/genetics , LIM Domain Proteins/geneticsABSTRACT
BACKGROUND: Chronic kidney disease (CKD) poses a significant health risk in contemporary society. Current CKD treatments primarily involve renin-angiotensin-aldosterone system inhibitors and mineralocorticoid receptor antagonists, albeit associated with hyperkalemia risks. A novel selective mineralocorticoid receptor antagonist, finerenone, offers a promising, safer alternative for CKD therapy. This review comprehensively assesses the role and efficacy of finerenone in CKD treatment by analyzing clinical and animal studies. Emerging evidence consistently supports finerenone's ability to effectively slow the progression of CKD. By targeting the mineralocorticoid receptor, finerenone not only mitigates renal damage but also exhibits a favorable safety profile, minimizing hyperkalemia concerns. CONCLUSION: Finerenone emerges as a valuable addition to CKD therapy, demonstrating potential benefits in delaying CKD progression while minimizing side effects. Nevertheless, further clinical trials are necessary to provide a comprehensive understanding of its safety and efficacy.
Subject(s)
Diabetes Mellitus, Type 2 , Hyperkalemia , Renal Insufficiency, Chronic , Animals , Mineralocorticoid Receptor Antagonists/adverse effects , Hyperkalemia/chemically induced , Hyperkalemia/drug therapy , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/drug therapy , Renal Insufficiency, Chronic/chemically induced , Naphthyridines/adverse effects , Diabetes Mellitus, Type 2/complicationsABSTRACT
Diabetic kidney disease (DKD) is a serious complication of diabetes and is the primary cause of end-stage renal disease. Current treatment strategies primarily focus on the inhibition of the renin-angiotensin-aldosterone system and the attainment of blood glucose control. Although current medical therapies for DKD have been shown to delay disease progression and improve long-term outcomes, their efficacy is limited and they may be restricted in certain cases, particularly when hyperkalemia is present. Traditional Chinese medicine (TCM) treatment has emerged as a significant complementary approach for DKD. TCM monomers, derived from various Chinese herbs, have been found to modulate multiple therapeutic targets and exhibit a broad range of therapeutic effects in patients with DKD. This review aims to summarize the mechanisms of action of TCM monomers in the treatment of DKD, based on findings from clinical trials, as well as cell and animal studies. The results of these investigations demonstrate the potential effective use of TCM monomers in treating or preventing DKD, offering a promising new direction for future research in the field. By providing a comprehensive overview of the mechanisms and efficacy of TCM monomers in DKD, this review highlights the potential of these natural compounds as alternative therapeutic options for improving outcomes in patients with DKD.
Subject(s)
Diabetes Mellitus , Diabetic Nephropathies , Kidney Failure, Chronic , Humans , Diabetic Nephropathies/drug therapy , Renin-Angiotensin SystemABSTRACT
Bisphenol A (BPA) is a widely used environmental estrogen found in a variety of products, including food packaging, canned goods, baby bottle soothers, reusable cups, medical devices, tableware, dental sealants, and other consumer goods. This substance has been found to have detrimental effects on both the environment and human health, particularly on the reproductive, immune, embryonic development, nervous, endocrine, and respiratory systems. This paper aims to provide a comprehensive review of the effects of BPA on the neuroendocrine system, with a primary focus on its impact on the brain, neurons, oligodendrocytes, neural stem cell proliferation, DNA damage, and behavioral development. Additionally, the review explores the clinical implications of BPA, specifically examining its role in the onset and progression of various diseases associated with the neuroendocrine metabolic system. By delving into the mechanistic analysis and clinical implications, this review aims to serve as a valuable resource for studying the impacts of BPA exposure on organisms.
Subject(s)
Ecotoxicology , Phenols , Humans , Phenols/toxicity , Benzhydryl Compounds/toxicity , Neurosecretory SystemsABSTRACT
Aging is a progressive and irreversible pathophysiological process that manifests as the decline in tissue and cellular functions, along with a significant increase in the risk of various aging-related diseases, including metabolic diseases. While advances in modern medicine have significantly promoted human health and extended human lifespan, metabolic diseases such as obesity and type 2 diabetes among the older adults pose a major challenge to global public health as societies age. Therefore, understanding the complex interaction between risk factors and metabolic diseases is crucial for promoting well-being and healthy aging. This review article explores the environmental and behavioral risk factors associated with metabolic diseases and their impact on healthy aging. The environment, including an obesogenic environment and exposure to environmental toxins, is strongly correlated with the rising prevalence of obesity and its comorbidities. Behavioral factors, such as diet, physical activity, smoking, alcohol consumption, and sleep patterns, significantly influence the risk of metabolic diseases throughout aging. Public health interventions targeting modifiable risk factors can effectively promote healthier lifestyles and prevent metabolic diseases. Collaboration between government agencies, healthcare providers and community organizations is essential for implementing these interventions and creating supportive environments that foster healthy aging.
Subject(s)
Diabetes Mellitus, Type 2 , Healthy Aging , Metabolic Diseases , Humans , Aged , Public Health , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/etiology , Risk Factors , Obesity/epidemiology , Metabolic Diseases/epidemiologyABSTRACT
Subcellular organelles dysfunction is implicated in various diseases, including metabolic diseases, neurodegenerative diseases, cancer, and cardiovascular diseases. BAM15, a selective mitochondrial uncoupler, has emerged as a promising therapeutic agent due to its ability to enhance mitochondrial respiration and metabolic flexibility. By disrupting the coupling between electron transport and ATP synthesis, BAM15 dissipates the proton gradient, leading to increased mitochondrial respiration and energy expenditure. This review provides a comprehensive overview of BAM15, including its mechanism of action and potential therapeutic applications in diverse disease contexts. BAM15 has shown promise in obesity by increasing energy expenditure and reducing fat accumulation. In diabetes, it improves glycemic control and reverses insulin resistance. Additionally, BAM15 has potential in non-alcoholic fatty liver disease, sepsis, and cardiovascular diseases by mitigating oxidative stress, modulating inflammatory responses, and promoting cardioprotection. The safety profile of BAM15 is encouraging, with minimal adverse effects and remarkable tolerability. However, challenges such as its high lipophilicity and the need for alternative delivery methods need to be addressed. Further research is necessary to fully understand the therapeutic potential of BAM15 and optimize its application in clinical settings.
Subject(s)
Cardiovascular Diseases , Non-alcoholic Fatty Liver Disease , Humans , Cardiovascular Diseases/metabolism , Mitochondria/metabolism , Obesity/metabolism , Energy Metabolism/physiology , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/metabolismABSTRACT
Metabolic diseases pose a significant global health challenge, characterized by an imbalance in metabolism and resulting in various complications. Secreted frizzled-related protein 5 (SFRP5), an adipokine known for its anti-inflammatory properties, has gained attention as a promising therapeutic target for metabolic diseases. SFRP5 acts as a key regulator in the Wnt signaling pathway, exerting its influence on critical cellular functions including proliferation, differentiation, and migration. Its significance extends to the realm of adipose tissue biology, where it plays a central role in regulating inflammation, insulin resistance, adipogenesis, lipid metabolism, glucose homeostasis, and energy balance. By inhibiting Wnt signaling, SFRP5 facilitates adipocyte growth, promotes lipid accumulation, and contributes to a decrease in oxidative metabolism. Lifestyle interventions and pharmacological treatments have shown promise in increasing SFRP5 levels and protecting against metabolic abnormalities. SFRP5 is a pivotal player in metabolic diseases and presents itself as a promising therapeutic target. An overview of SFRP5 and its involvement in metabolic disorders and metabolism is provided in this comprehensive review. By elucidating these aspects, valuable insights can be gained to foster the development of effective strategies in combating metabolic diseases.
Subject(s)
Insulin Resistance , Wnt Signaling Pathway , Humans , Secreted Frizzled-Related Proteins , Eye Proteins/metabolism , Membrane Proteins/metabolism , Adaptor Proteins, Signal Transducing/metabolismABSTRACT
The Wnt signaling system is a critical pathway that regulates embryonic development and adult homeostasis. Secreted frizzled-related proteins (SFRPs) are extracellular inhibitors of Wnt signaling that act by binding directly to Wnt ligands or Frizzled receptors. SFRPs can act as anti-Wnt agents and suppress cancer growth by blocking the action of Wnt ligands. However, SFRPs are often silenced by promoter methylation in cancer cells, resulting in hyperactivation of the Wnt pathway. Epigenetic modifiers can reverse this silencing and restore SFRPs expression. Despite the potential of SFRPs as a therapeutic target, the effects of SFRPs on tumor development remain unclear. Therefore, a review of the expression of various members of the SFRPs family in different cancers and their potential as therapeutic targets is warranted. This review aims to summarize the current knowledge of SFRPs in cancer, focusing on their expression patterns and their potential as novel therapeutic targets.
Subject(s)
Neoplasms , Wnt Signaling Pathway , Adult , Female , Pregnancy , Humans , Secreted Frizzled-Related Proteins , Ligands , Homeostasis , Frizzled Receptors/genetics , Neoplasms/drug therapy , Neoplasms/geneticsABSTRACT
Post-stroke depression (PSD) is a frequent and disabling complication of stroke that affects up to one-third of stroke survivors. The pathophysiology of PSD involves multiple mechanisms, including neurochemical, neuroinflammatory, neurotrophic, and neuroplastic changes. Astrocytes are a type of glial cell that is plentiful and adaptable in the central nervous system. They play key roles in various mechanisms by modulating neurotransmission, inflammation, neurogenesis, and synaptic plasticity. This review summarizes the latest evidence of astrocyte involvement in PSD from human and animal studies, focusing on the alterations of astrocyte markers and functions in relation to monoamine neurotransmitters, inflammatory cytokines, brain-derived neurotrophic factor, and glutamate excitotoxicity. We also discuss the potential therapeutic implications of targeting astrocytes for PSD prevention and treatment. Astrocytes could be new candidates for antidepressant medications and other interventions that aim to restore astrocyte homeostasis and function in PSD. Astrocytes could be new candidates for antidepressant medications and other interventions that aim to restore astrocyte homeostasis and function in PSD.
Subject(s)
Astrocytes , Stroke , Animals , Humans , Astrocytes/metabolism , Depression/etiology , Depression/drug therapy , Synaptic Transmission , Antidepressive Agents/metabolism , Inflammation/metabolismABSTRACT
Importance: Diabetes in children is a global epidemic that causes various medical conditions associated with an increased incidence of premature death. Objective: To investigate the trends in diabetes incidence, mortality, and disability-adjusted life-years (DALYs) in children, with risk factors for diabetes-associated death, from 1990 to 2019. Design, Setting, and Participants: This was a cross-sectional study that used data from the Global Burden of Diseases (GBD) 2019 in 204 countries and territories. Children with diabetes who were aged 0 to 14 years were included in the analysis. Data were analyzed from December 28, 2022, to January 10, 2023. Exposure: Childhood diabetes from 1990 to 2019. Main Outcome Measures: Incidence, all-cause and cause-specific deaths, DALYs, and corresponding estimated annual percentage changes (EAPCs). These trends were stratified according to region, country, age, sex, and Sociodemographic Index (SDI). Results: A total of 1â¯449â¯897 children (738â¯923 male [50.96%]) were included in the analysis. In 2019, there were 227â¯580 incident cases of childhood diabetes worldwide. Cases of childhood diabetes increased by 39.37% (95% uncertainty interval [UI], 30.99%-45.45%) from 1990 to 2019. Over 3 decades, diabetes-associated deaths decreased from 6719 (95% UI, 4823-8074) to 5390 (95% UI, 4450-6507). The global incidence rate increased from 9.31 (95% UI, 6.56-12.57) to 11.61 (95% UI, 7.98-15.98) per 100â¯000 population; however, the diabetes-associated death rate decreased from 0.38 (95% UI, 0.27-0.46) to 0.28 (95% UI, 0.23-0.33) per 100â¯000 population. Among the 5 SDI regions, the low SDI region had the highest childhood diabetes-associated mortality rate in 2019. Regionally, North Africa and the Middle East had the largest increase in incidence (EAPC, 2.06; 95% CI, 1.94-2.17). Among 204 countries, Finland had the highest national incidence of childhood diabetes in 2019 (31.60 per 100â¯000 population; 95% UI, 22.65-40.36), Bangladesh had the highest diabetes-associated mortality rate (1.16 per 100â¯000 population; 95% UI, 0.51-1.70), and the United Republic of Tanzania had the highest DALYs rate (100.16 per 100â¯000 population; 95% UI, 63.01-155.88). Globally, environmental/occupational risk, nonoptimal temperature, high temperature, and low temperature were key risk factors for childhood diabetes-associated mortality in 2019. Conclusions and Relevance: Childhood diabetes is an increasing global health challenge with rising incidence. Results of this cross-sectional study suggest that despite the global decline in deaths and DALYs, the number of deaths and DALYs remains high among children with diabetes, especially in low SDI regions. Improved understanding of the epidemiology of diabetes in children may facilitate prevention and control.
Subject(s)
Diabetes Mellitus , Global Burden of Disease , Humans , Male , Child , Quality-Adjusted Life Years , Cross-Sectional Studies , Risk Factors , Global Health , Incidence , Diabetes Mellitus/epidemiologyABSTRACT
Diabetes is a multifactorial disorder that increases mortality and disability due to its complications. A key driver of these complications is nonenzymatic glycation, which generates advanced glycation end-products (AGEs) that impair tissue function. Therefore, effective nonenzymatic glycation prevention and control strategies are urgently needed. This review comprehensively describes the molecular mechanisms and pathological consequences of nonenzymatic glycation in diabetes and outlines various anti-glycation strategies, such as lowering plasma glucose, interfering with the glycation reaction, and degrading early and late glycation products. Diet, exercise, and hypoglycemic medications can reduce the onset of high glucose at the source. Glucose or amino acid analogs such as flavonoids, lysine and aminoguanidine competitively bind to proteins or glucose to block the initial nonenzymatic glycation reaction. In addition, deglycation enzymes such as amadoriase, fructosamine-3-kinase, parkinson's disease protein, glutamine amidotransferase-like class 1 domain-containing 3A and terminal FraB deglycase can eliminate existing nonenzymatic glycation products. These strategies involve nutritional, pharmacological, and enzymatic interventions that target different stages of nonenzymatic glycation. This review also emphasizes the therapeutic potential of anti-glycation drugs for preventing and treating diabetes complications.
Subject(s)
Diabetes Mellitus , Humans , Diabetes Mellitus/drug therapy , Diabetes Mellitus/metabolism , Glycation End Products, Advanced/metabolism , Maillard Reaction , Proteins/chemistry , Glucose/chemistryABSTRACT
Aims: Pancreatic cancer (PC) is a malignant tumor with a strong invasive nature and low survival rate. We aimed to estimate the PC burden at the global, regional, and national levels in 204 countries from 1990 to 2019. Methods: Detailed data, including the incidence, death, and disability-adjusted life years (DALYs), were analyzed from the Global Burden of Diseases Study 2019. Results: Globally, there were 530,297 (486,175-573,635) incident cases and 531,107 (491,948-566,537) deaths from PC in 2019. The age-standardized incidence rate (ASIR) was 6.6 (6-7.1), and the age-standardized mortality rate (ASMR) was 6.6 (6.1-7.1) per 100,000 person-years. PC caused 11,549,016 (10,777,405-12,338,912) DALYs, with an age-standardized rate of 139.6 (130.2-149.1) per 100,000 person-years. There were increases in estimated annual percentage changes (EAPCs) of ASIR (0.83; 0.78-0.87), ASMR (0.77; 0.73-0.81), and age-standardized DALYs rate (ASDR) (0.67; 0.63-0.71). The global number of incident cases increased by 168.7%, from 197,348 (188,604-203,971) to 530,297 (486,175-573,635); the number of deaths increased by 168.2% from 198,051 (189,329-204,763) to 531,107 (491,948-566,537); and total DALYs increased by 148.5% from 4,647,207 (4,465,440-4,812,129) to 11,549,016 (10,777,405-12,338,912). East Asia and China recorded the highest number of incident cases, deaths, and DALYs. The proportion of deaths was attributable to smoking (21.4%), elevated fasting glucose (9.1%), and high BMI (6%). Conclusions: Our study updated the epidemiological trends and risk factors for PC. PC remains a major hazard to the sustainability of health systems worldwide, with an increasing incidence rate and mortality from 1990 to 2019. More targeted strategies are required to prevent and treat PC.