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Background: Given the rapidly growing burden of cardiovascular disease (CVD) in Asia, this study forecasts the CVD burden and associated risk factors in Asia from 2025 to 2050. Methods: Data from the Global Burden of Disease 2019 study was used to construct regression models predicting prevalence, mortality, and disability-adjusted life years (DALYs) attributed to CVD and risk factors in Asia in the coming decades. Findings: Between 2025 and 2050, crude cardiovascular mortality is expected to rise 91.2% despite a 23.0% decrease in the age-standardised cardiovascular mortality rate (ASMR). Ischaemic heart disease (115 deaths per 100,000 population) and stroke (63 deaths per 100,000 population) will remain leading drivers of ASMR in 2050. Central Asia will have the highest ASMR (676 deaths per 100,000 population), more than three-fold that of Asia overall (186 deaths per 100,000 population), while high-income Asia sub-regions will incur an ASMR of 22 deaths per 100,000 in 2050. High systolic blood pressure will contribute the highest ASMR throughout Asia (105 deaths per 100,000 population), except in Central Asia where high fasting plasma glucose will dominate (546 deaths per 100,000 population). Interpretation: This forecast forewarns an almost doubling in crude cardiovascular mortality by 2050 in Asia, with marked heterogeneity across sub-regions. Atherosclerotic diseases will continue to dominate, while high systolic blood pressure will be the leading risk factor. Funding: This was supported by the NUHS Seed Fund (NUHSRO/2022/058/RO5+6/Seed-Mar/03), National Medical Research Council Research Training Fellowship (MH 095:003/008-303), National University of Singapore Yong Loo Lin School of Medicine's Junior Academic Fellowship Scheme, NUHS Clinician Scientist Program (NCSP2.0/2024/NUHS/NCWS) and the CArdiovascular DiseasE National Collaborative Enterprise (CADENCE) National Clinical Translational Program (MOH-001277-01).
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Food-derived extracellular vesicles (FEVs) are nanoscale membrane vesicles obtained from dietary materials such as breast milk, plants and probiotics. Distinct from other EVs, FEVs can survive the harsh degrading conditions in the gastrointestinal tract and reach the intestines. This unique feature allows FEVs to be promising prebiotics in health and oral nanomedicine for gut disorders, such as inflammatory bowel disease. Interestingly, therapeutic effects of FEVs have recently also been observed in non-gastrointestinal diseases. However, the mechanisms remain unclear or even mysterious. It is speculated that orally administered FEVs could enter the bloodstream, reach remote organs, and thus exert therapeutic effects therein. However, emerging evidence suggests that the amount of FEVs reaching organs beyond the gastrointestinal tract is marginal and may be insufficient to account for the significant therapeutic effects achieved regarding diseases involving remote organs such as the liver. Thus, we herein propose that FEVs primarily act locally in the intestine by modulating intestinal microenvironments such as barrier integrity and microbiota, thereby eliciting therapeutic impact remotely on the liver in non-gastrointestinal diseases via the gut-liver axis. Likewise, drugs delivered to the gastrointestinal system through FEVs may act via the gut-liver axis. As the liver is the main metabolic hub, the intestinal microenvironment may be implicated in other metabolic diseases. In fact, many patients with non-alcoholic fatty liver disease, obesity, diabetes and cardiovascular disease suffer from a leaky gut and dysbiosis. In this review, we provide an overview of the recent progress in FEVs and discuss their biomedical applications as therapeutic agents and drug delivery systems, highlighting the pivotal role of the gut-liver axis in the mechanisms of action of FEVs for the treatment of gut disorders and metabolic diseases.
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Vesículas Extracelulares , Hígado , Humanos , Vesículas Extracelulares/metabolismo , Hígado/metabolismo , Microbioma Gastrointestinal , Animales , Tracto Gastrointestinal/metabolismo , AlimentosRESUMEN
AIM: Patients with metabolic dysfunction-associated steatotic liver disease (MASLD) are at increased risk of incident cardiovascular disease. However, the clinical characteristics and prognostic importance of MASLD in patients presenting with acute myocardial infarction (AMI) have yet to be examined. METHODS: This study compared the characteristics and outcomes of patients with and without MASLD presenting with AMI at a tertiary centre in Singapore. MASLD was defined as hepatic steatosis, with at least one of five metabolic criteria. Hepatic steatosis was determined using the Hepatic Steatosis Index. Propensity score matching was performed to adjust for age and sex. The Kaplan-Meier curve was constructed for long-term all-cause mortality. Cox regression analysis was used to investigate independent predictors of long-term all-cause mortality. RESULTS: In this study of 4446 patients with AMI, 2223 patients with MASLD were matched with patients without MASLD using propensity scores. The mean follow-up duration was 3.4 ± 2.4 years. The MASLD group had higher rates of obesity, diabetes and chronic kidney disease than their counterparts. Patients with MASLD had early excess all-cause mortality (6.8% vs. 3.6%, p < .001) at 30 days, with unfavourable mortality rates sustained in the long-term (18.3% vs. 14.5%, p = .001) compared with those without MASLD. After adjustment, MASLD remained independently associated with higher long-term all-cause mortality (hazard ratio 1.330, 95% confidence interval 1.106-1.598, p = .002). CONCLUSION: MASLD embodies a higher burden of metabolic dysfunction and is an independent predictor of long-term mortality in the AMI population. Its early identification may be beneficial for risk stratification and provide therapeutic targets for secondary preventive strategies in AMI.
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Infarto del Miocardio , Puntaje de Propensión , Humanos , Masculino , Femenino , Infarto del Miocardio/mortalidad , Infarto del Miocardio/complicaciones , Infarto del Miocardio/epidemiología , Persona de Mediana Edad , Pronóstico , Anciano , Singapur/epidemiología , Hígado Graso/complicaciones , Hígado Graso/mortalidad , Factores de Riesgo , Estudios RetrospectivosRESUMEN
ApoE regulates neurogenesis, although how it influences genetic programs remains elusive. Cortical neurons induced from isogenic control and ApoE-/- human neural stem cells (NSCs) recapitulated key transcriptomic signatures of in vivo counterparts identified from single-cell human midbrain. Surprisingly, ApoE expression in NSC and neural progenitor cells (NPCs) is not required for differentiation. Instead, ApoE prevents the over-proliferation of non-neuronal cells during extended neuronal culture when it is not expressed. Elevated miR-199a-5p level in ApoE-/- cells lowers the EZH1 protein and the repressive H3K27me3 mark, a phenotype rescued by miR-199a-5p steric inhibitor. Reduced H3K27me3 at genes linked to extracellular matrix organization and angiogenesis in ApoE-/- NPC correlates with their aberrant expression and phenotypes in neurons. Interestingly, the ApoE coding sequence, which contains many predicted miR-199a-5p binding sites, can repress miR-199a-5p without translating into protein. This suggests that ApoE maintains neurons integrity through the target-directed miRNA degradation of miR-199a-5p, imparting the H3K27me3-mediated repression of non-neuronal genes during differentiation.
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The most common chronic liver illness, non-alcoholic fatty liver disease (NAFLD), refers to a range of abnormalities of the liver with varying degrees of steatosis. When the clinical symptoms including liver damage, inflammation, and fibrosis, are added to the initial steatosis, NAFLD becomes non-alcoholic steatohepatitis (NASH), the problematic and severe stage. The diagnosis of NASH at the right time could therefore effectively prevent deterioration of the disease. Considering that platelets (PLTs) could migrate to the sites of inflamed liver sinusoids with oxidative stress during the development of NASH, we purified the PLTs from fresh blood and engineered their surface with hydrogen peroxide (H2O2) responsive fluorescent probe (5-DP) through lipid fusion. The engineered PLT-DPs were recruited and trapped in the inflammation foci of the liver with NASH through interaction with the extracellular matrix, including hyaluronan and Kupffer cells. Additionally, the fluorescence of 5-DP on the surface of PLT-DP was significantly enhanced upon reacting with the elevated level of H2O2 in the NASH liver. Thus, PLT-DP has great promise for NASH fluorescence imaging with high selectivity and sensitivity.
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Enfermedad del Hígado Graso no Alcohólico , Humanos , Peróxido de Hidrógeno , Hígado/patología , Cirrosis Hepática/patología , Inflamación/patologíaRESUMEN
BACKGROUND & AIMS: The progression of metabolic dysfunction-associated steatotic liver disease (MASLD) has been found to manifest in a series of hepatic and extrahepatic complications. A comprehensive meta-analysis of the longitudinal outcomes associated with MASLD has yet to be conducted. METHODS: To investigate the longitudinal outcomes associated with MASLD, Medline and Embase databases were searched to identify original studies that evaluated the longitudinal risks of incident clinical outcomes among MASLD patients compared with non-MASLD individuals. DerSimonian Laird random-effects meta-analysis was performed. Pooled effect estimates were calculated, and heterogeneity among studies was evaluated. RESULTS: One hundred twenty-nine studies were included in the meta-analysis. Meta-analysis revealed a significant increase in the risk of cardiovascular outcomes (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.27-1.60; P < .01), various metabolic outcomes such as incident hypertension (HR, 1.75; 95% CI, 1.46-2.08; P < .01), diabetes (HR, 2.56; 95% CI, 2.10-3.13; P < .01), pre-diabetes (HR, 1.69; 95% CI, 1.22-2.35; P < .01), metabolic syndrome (HR, 2.57; 95% CI, 1.13-5.85; P = .02), chronic kidney disease (HR, 1.38; 95% CI, 1.27-1.50; P < .01), as well as all cancers (HR, 1.54; 95% CI, 1.35-1.76; P < .01) among MASLD patients compared with non-MASLD individuals. By subgroup analysis, MASLD patients with advanced liver disease (HR, 3.60; 95% CI, 2.10-6.18; P < .01) were also found to be associated with a significantly greater risk (P = .02) of incident diabetes than those with less severe MASLD (HR, 1.63; 95% CI, 1.0-2.45; P = .02) when compared with non-MASLD. CONCLUSIONS: The present study emphasizes the association between MASLD and its clinical outcomes including cardiovascular, metabolic, oncologic, and other outcomes. The multisystemic nature of MASLD found in this analysis requires treatment targets to reduce systemic events and end organ complications.
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Diabetes Mellitus , Hígado Graso , Síndrome Metabólico , Humanos , Hígado Graso/complicaciones , Hígado Graso/epidemiología , Síndrome Metabólico/complicaciones , Síndrome Metabólico/epidemiología , CardiooncologíaRESUMEN
BACKGROUND: High body mass index (BMI) is a major risk factor for cancer development, but its impact on the global burden of cancer remains unclear. METHODS: We estimated global and regional temporal trends in the burden of cancer attributable to high BMI, and the contributions of various cancer types using the framework of the Global Burden of Disease Study. RESULTS: From 2010 to 2019, there was a 35 % increase in deaths and a 34 % increase in disability-adjusted life-years from cancers attributable to high BMI. The age-standardized death rates for cancer attributable to high BMI increased over the study period (annual percentage change [APC] +0.48 %, 95 % CI 0.22 to 0.74 %). The greatest number of deaths from cancer attributable to high BMI occurred in Europe, but the fastest-growing age-standardized death rates and disability-adjusted life-years occurred in Southeast Asia. Liver cancer was the fastest-growing cause of cancer mortality (APC: 1.37 %, 95 % CI 1.25 to 1.49 %) attributable to high BMI. CONCLUSION: The global burden of cancer-related deaths attributable to high BMI has increased substantially from 2010 to 2019. The greatest increase in age-standardized death rates occurred in Southeast Asia, and liver cancer is the fastest-growing cause of cancer mortality attributable to high BMI. Urgent and sustained measures are required at a global and regional level to reverse these trends and slow the growing burden of cancer attributed to high BMI.
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Neoplasias Hepáticas , Humanos , Índice de Masa Corporal , Años de Vida Ajustados por Calidad de Vida , Factores de Riesgo , Europa (Continente)/epidemiologíaRESUMEN
BACKGROUND: Dilated cardiomyopathy (DCM) is a severe, non-ischemic heart disease which ultimately results in heart failure (HF). Decades of research on DCM have revealed diverse aetiologies. Among them, familial DCM is the major form of DCM, with pathogenic variants in LMNA being the second most common form of autosomal dominant DCM. LMNA DCM is a multifactorial and complex disease with no specific treatment thus far. Many studies have demonstrated that perturbing candidates related to various dysregulated pathways ameliorate LMNA DCM. However, it is unknown whether these candidates could serve as potential therapeutic targets especially in long term efficacy. METHODS: We evaluated 14 potential candidates including Lmna gene products (Lamin A and Lamin C), key signaling pathways (Tgfß/Smad, mTor and Fgf/Mapk), calcium handling, proliferation regulators and modifiers of LINC complex function in a cardiac specific Lmna DCM model. Positive candidates for improved cardiac function were further assessed by survival analysis. Suppressive roles and mechanisms of these candidates in ameliorating Lmna DCM were dissected by comparing marker gene expression, Tgfß signaling pathway activation, fibrosis, inflammation, proliferation and DNA damage. Furthermore, transcriptome profiling compared the differences between Lamin A and Lamin C treatment. RESULTS: Cardiac function was restored by several positive candidates (Smad3, Yy1, Bmp7, Ctgf, aYAP1, Sun1, Lamin A, and Lamin C), which significantly correlated with suppression of HF/fibrosis marker expression and cardiac fibrosis in Lmna DCM. Lamin C or Sun1 shRNA administration achieved consistent, prolonged survival which highly correlated with reduced heart inflammation and DNA damage. Importantly, Lamin A treatment improved but could not reproduce long term survival, and Lamin A administration to healthy hearts itself induced DCM. Mechanistically, we identified this lapse as caused by a dose-dependent toxicity of Lamin A, which was independent from its maturation. CONCLUSIONS: In vivo candidate evaluation revealed that supplementation of Lamin C or knockdown of Sun1 significantly suppressed Lmna DCM and achieve prolonged survival. Conversely, Lamin A supplementation did not rescue long term survival and may impart detrimental cardiotoxicity risk. This study highlights a potential of advancing Lamin C and Sun1 as therapeutic targets for the treatment of LMNA DCM.
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Cardiomiopatías , Cardiomiopatía Dilatada , Humanos , Cardiomiopatía Dilatada/genética , Cardiomiopatía Dilatada/patología , Lamina Tipo A/genética , Lamina Tipo A/metabolismo , Fibrosis , Inflamación/complicaciones , Factor de Crecimiento Transformador beta , MutaciónRESUMEN
Dietary modifications can help prevent many cardiovascular disease (CVD) events. Endothelial progenitor cells (EPCs) actively contribute to cardiovascular system maintenance and could function as surrogate markers for evaluating improvement in cardiovascular health resulting from nutritional interventions. This review summarizes the latest research progress on the impact of food and nutrients on EPCs, drawing on evidence from human, animal, and in vitro studies. Additionally, current trends and challenges faced in the field are highlighted. Findings from studies examining cells as EPCs are generally consistent, demonstrating that a healthy diet, such as the Mediterranean diet or a supervised diet for overweight people, specific foods like olive oil, fruit, vegetables, red wine, tea, chia, and nutraceuticals, and certain nutrients such as polyphenols, unsaturated fats, inorganic nitrate, and vitamins, generally promote higher EPC numbers and enhanced EPC function. Conversely, an unhealthy diet, such as one high in sugar substitutes, salt, or fructose, impairs EPC function. Research on outgrowth EPCs has revealed that various pathways are involved in the modulation effects of food and nutrients. The potential of EPCs as a biomarker for assessing the effectiveness of nutritional interventions in preventing CVDs is immense, while further clarification on definition and characterization of EPCs is required.
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Extracellular vesicles (EVs) can be produced from red blood cells (RBCs) on a large scale and used to deliver therapeutic payloads efficiently. However, not much is known about the native biological properties of RBCEVs. Here, we demonstrate that RBCEVs are primarily taken up by macrophages and monocytes. This uptake is an active process, mediated mainly by endocytosis. Incubation of CD14+ monocytes with RBCEVs induces their differentiation into macrophages with an Mheme-like phenotype, characterized by upregulation of heme oxygenase-1 (HO-1) and the ATP-binding cassette transporter ABCG1. Moreover, macrophages that take up RBCEVs exhibit a reduction in surface CD86 and decreased secretion of TNF-α under inflammatory stimulation. The upregulation of HO-1 is attributed to heme derived from haemoglobin in RBCEVs. Heme is released from internalized RBCEVs in late endosomes and lysosomes via the heme transporter, HRG1. Consequently, RBCEVs exhibit the ability to attenuate foam cell formation from oxidized low-density lipoproteins (oxLDL)-treated macrophages in vitro and reduce atherosclerotic lesions in ApoE knockout mice on a high-fat diet. In summary, our study reveals the uptake mechanism of RBCEVs and their delivery of heme to macrophages, suggesting the potential application of RBCEVs in the treatment of atherosclerosis.
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Aterosclerosis , Vesículas Extracelulares , Animales , Ratones , Células Espumosas/metabolismo , Células Espumosas/patología , Hemo/metabolismo , Vesículas Extracelulares/metabolismo , Macrófagos/metabolismo , Eritrocitos/metabolismo , EndocitosisRESUMEN
Atherosclerosis is a chronic inflammatory vascular disease that is characterized by the accumulation of lipids and immune cells in plaques built up inside artery walls. Docosahexaenoic acid (DHA, 22:6n-3), an omega-3 polyunsaturated fatty acid (PUFA), which exerts anti-inflammatory and antioxidant properties, has long been purported to be of therapeutic benefit to atherosclerosis patients. However, large clinical trials have yielded inconsistent data, likely due to variations in the formulation, dosage, and bioavailability of DHA following oral intake. To fully exploit its potential therapeutic effects, we have developed an injectable liposomal DHA formulation intended for intravenous administration as a plaque-targeted nanomedicine. The liposomal formulation protects DHA against chemical degradation and increases its local concentration within atherosclerotic lesions. Mechanistically, DHA liposomes are readily phagocytosed by activated macrophages, exert potent anti-inflammatory and antioxidant effects, and inhibit foam cell formation. Upon intravenous administration, DHA liposomes accumulate preferentially in atherosclerotic lesional macrophages and promote polarization of macrophages towards an anti-inflammatory M2 phenotype, resulting in attenuation of atherosclerosis progression in both ApoE-/- and Ldlr-/- experimental models. Plaque composition analysis demonstrates that liposomal DHA inhibits macrophage infiltration, reduces lipid deposition, and increases collagen content, thus improving the stability of atherosclerotic plaques against rupture. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) further reveals that DHA liposomes can partly restore the complex lipid profile of the plaques to that of early-stage plaques. In conclusion, DHA liposomes offer a promising approach for applying DHA to stabilize atherosclerotic plaques and attenuate atherosclerosis progression, thereby preventing atherosclerosis-related cardiovascular events.
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Aterosclerosis , Placa Aterosclerótica , Humanos , Placa Aterosclerótica/metabolismo , Ácidos Docosahexaenoicos/uso terapéutico , Ácidos Docosahexaenoicos/farmacología , Liposomas/uso terapéutico , Aterosclerosis/metabolismo , Antiinflamatorios/uso terapéutico , Apolipoproteínas E/genéticaRESUMEN
Wound healing is a dynamic process that involves a series of molecular and cellular events aimed at replacing devitalized and missing cellular components and/or tissue layers. Recently, extracellular vesicles (EVs), naturally cell-secreted lipid membrane-bound vesicles laden with biological cargos including proteins, lipids, and nucleic acids, have drawn wide attention due to their ability to promote wound healing and tissue regeneration. However, current exploitation of EVs as therapeutic agents is limited by their low isolation yields and tedious isolation processes. To circumvent these challenges, bioinspired cell-derived nanovesicles (CDNs) that mimic EVs were obtained by shearing mesenchymal stem cells (MSCs) through membranes with different pore sizes. Physical characterisations and high-throughput proteomics confirmed that MSC-CDNs mimicked MSC-EVs. Moreover, these MSC-CDNs were efficiently uptaken by human dermal fibroblasts and demonstrated a dose-dependent activation of MAPK signalling pathway, resulting in enhancement of cell proliferation, cell migration, secretion of growth factors and extracellular matrix proteins, which all promoted tissue regeneration. Of note, MSC-CDNs enhanced angiogenesis in human dermal microvascular endothelial cells in a 3D PEG-fibrin scaffold and animal model, accelerating wound healing in vitro and in vivo. These findings suggest that MSC-CDNs could replace both whole cells and EVs in promoting wound healing and tissue regeneration.
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Extracellular vesicles (EVs), which are miniaturised carriers loaded with functional proteins, lipids, and nucleic acid material, are naturally secreted by cells and show intrinsic pharmacological effects in several conditions. As such, they have the potential to be used for the treatment of various human diseases. However, the low isolation yield and laborious purification process are obstacles to their translation for clinical use. To overcome this problem, our lab developed cell-derived nanovesicles (CDNs), which are EV mimetics produced by shearing cells through membrane-fitted spin cups. To evaluate the similarities between EVs and CDNs, we compare the physical properties and biochemical composition of monocytic U937 EVs and U937 CDNs. Besides having similar hydrodynamic diameters, the produced CDNs had proteomic, lipidomic, and miRNA profiles with key communalities compared to those of natural EVs. Further characterisation was conducted to examine if CDNs could exhibit similar pharmacological activities and immunogenicity when administered in vivo. Consistently, CDNs and EVs modulated inflammation and displayed antioxidant activities. EVs and CDNs both did not exert immunogenicity when administered in vivo. Overall, CDNs could serve as a scalable and efficient alternative to EVs for further translation into clinical use.
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Monitoring X-ray radiation in the gastrointestinal tract can enhance the precision of radiotherapy in patients with gastrointestinal cancer. Here we report the design and performance, in the gastrointestinal tract of rabbits, of a swallowable X-ray dosimeter for the simultaneous real-time monitoring of absolute absorbed radiation dose and of changes in pH and temperature. The dosimeter consists of a biocompatible optoelectronic capsule containing an optical fibre, lanthanide-doped persistent nanoscintillators, a pH-sensitive polyaniline film and a miniaturized system for the wireless readout of luminescence. The persistent luminescence of the nanoscintillators after irradiation can be used to continuously monitor pH without the need for external excitation. By using a neural-network-based regression model, we estimated the radiation dose from radioluminescence and afterglow intensity and temperature, and show that the dosimeter was approximately five times more accurate than standard methods for dose determination. Swallowable dosimeters may help to improve radiotherapy and to understand how radiotherapy affects tumour pH and temperature.
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Milk-derived extracellular vesicles (mEVs) have been proposed as a potential nanomedicine for intestinal disorders; however, their impact on intestinal barrier integrity in gut inflammation and associated metabolic diseases has not been explored yet. Here, mEVs derived from bovine and human breast milk exert similar protective effects on epithelial tight junction functionality in vitro, survive harsh gastrointestinal conditions ex vivo, and reach the colon in vivo. Oral administration of mEVs restores gut barrier integrity at multiple levels, including mucus, epithelial, and immune barriers, and prevents endotoxin translocation into the liver in chemical-induced experimental colitis and diet-induced nonalcoholic steatohepatitis (NASH), thereby alleviating gut disorders, their associated liver inflammation, and NASH. Oral administration of mEVs has potential in the treatment of gut inflammation and gut-liver axis-associated metabolic diseases via protection of intestinal barrier integrity.
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Colitis , Vesículas Extracelulares , Hepatitis , Enfermedad del Hígado Graso no Alcohólico , Humanos , Animales , Bovinos , Ratones , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Leche/metabolismo , Inflamación , Vesículas Extracelulares/metabolismo , Ratones Endogámicos C57BLRESUMEN
BACKGROUND: Low socioeconomic status (SES) is an important prognosticator amongst patients with acute coronary syndrome (ACS). This paper analysed the effects of SES on ACS outcomes. METHODS: Medline and Embase were searched for articles reporting outcomes of ACS patients stratified by SES using a multidimensional index, comprising at least 2 of the following components: Income, Education and Employment. A comparative meta-analysis was conducted using random-effects models to estimate the risk ratio of all-cause mortality in low SES vs high SES populations, stratified according to geographical region, study year, follow-up duration and SES index. RESULTS: A total of 29 studies comprising of 301,340 individuals were included, of whom 43.7% were classified as low SES. While patients of both SES groups had similar cardiovascular risk profiles, ACS patients of low SES had significantly higher risk of all-cause mortality (adjusted HR:1.19, 95%CI: 1.10-1.1.29, p < 0.001) compared to patients of high SES, with higher 1-year mortality (RR:1.08, 95%CI:1.03-1.13, p = 0.0057) but not 30-day mortality (RR:1.07, 95%CI:0.98-1.16, p = 0.1003). Despite having similar rates of ST-elevation myocardial infarction and non-ST-elevation ACS, individuals with low SES had lower rates of coronary revascularisation (RR:0.95, 95%CI:0.91-0.99, p = 0.0115) and had higher cerebrovascular accident risk (RR:1.25, 95%CI:1.01-1.55, p = 0.0469). Excess mortality risk was independent of region (p = 0.2636), study year (p = 0.7271) and duration of follow-up (p = 0.0604) but was dependent on the SES index used (p < 0.0001). CONCLUSION: Low SES is associated with increased mortality post-ACS, with suboptimal coronary revascularisation rates compared to those of high SES. Concerted efforts are needed to address the global ACS-related socioeconomic inequity. REGISTRATION AND PROTOCOL: The current study was registered with PROSPERO, ID: CRD42022347987.
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Síndrome Coronario Agudo , Infarto del Miocardio con Elevación del ST , Humanos , Síndrome Coronario Agudo/diagnóstico , Síndrome Coronario Agudo/cirugía , Pronóstico , Clase Social , Estatus Socioeconómico BajoRESUMEN
Background: Malnutrition and obesity are interdependent pathologies along the same spectrum. We examined global trends and projections of disability-adjusted life years (DALYs) and deaths from malnutrition and obesity until 2030. Methods: Using data from the 2019 Global Burden of Disease study involving 204 countries and territories, trends in DALYs and deaths were described for obesity and malnutrition from 2000 to 2019, stratified by geographical regions (as defined by WHO) and Socio-Demographic Index (SDI). Malnutrition was defined according to the 10th revision of International Classification of Diseases codes for nutritional deficiencies, stratified by malnutrition type. Obesity was measured via body mass index (BMI) using metrics related to national and subnational estimates, defined as BMI ≥25 kg/m2. Countries were stratified into low, low-middle, middle, high-middle, and high SDI bands. Regression models were constructed to predict DALYs and mortality up to 2030. Association between age-standardised prevalence of the diseases and mortality was also assessed. Findings: In 2019, age-standardised malnutrition-related DALYs was 680 (95% UI: 507-895) per 100,000 population. DALY rates decreased from 2000 to 2019 (-2.86% annually), projected to fall 8.4% from 2020 to 2030. Africa and low SDI countries observed highest malnutrition-related DALYs. Age-standardised obesity-related DALY estimates were 1933 (95% UI: 1277-2640). Obesity-related DALYs rose 0.48% annually from 2000 to 2019, predicted to increase by 39.8% from 2020 to 2030. Highest obesity-related DALYs were in Eastern Mediterranean and middle SDI countries. Interpretation: The ever-increasing obesity burden, on the backdrop of curbing the malnutrition burden, is predicted to rise further. Funding: None.
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Global estimates of prevalence, deaths, and disability-adjusted life years (DALYs) from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 were examined for metabolic diseases (type 2 diabetes mellitus [T2DM], hypertension, and non-alcoholic fatty liver disease [NAFLD]). For metabolic risk factors (hyperlipidemia and obesity), estimates were limited to mortality and DALYs. From 2000 to 2019, prevalence rates increased for all metabolic diseases, with the greatest increase in high socio-demographic index (SDI) countries. Mortality rates decreased over time in hyperlipidemia, hypertension, and NAFLD, but not in T2DM and obesity. The highest mortality was found in the World Health Organization Eastern Mediterranean region, and low to low-middle SDI countries. The global prevalence of metabolic diseases has risen over the past two decades regardless of SDI. Urgent attention is needed to address the unchanging mortality rates attributed to metabolic disease and the entrenched sex-regional-socioeconomic disparities in mortality.
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Diabetes Mellitus Tipo 2 , Hipertensión , Enfermedades Metabólicas , Enfermedad del Hígado Graso no Alcohólico , Humanos , Años de Vida Ajustados por Calidad de Vida , Diabetes Mellitus Tipo 2/epidemiología , Carga Global de Enfermedades , Factores de Riesgo , Obesidad/epidemiología , Enfermedades Metabólicas/epidemiologíaRESUMEN
Background: Anthracyclines such as doxorubicin remain a primary treatment for hematological malignancies and breast cancers. However, cardiotoxicity induced by anthracyclines, possibly leading to heart failure, severely limits their application. The pathological mechanisms of anthracycline-induced cardiac injury are believed to involve iron-overload-mediated formation of reactive oxygen species (ROS), mitochondrial dysfunction, and inflammation. The dietary thione, ergothioneine (ET), is avidly absorbed and accumulated in tissues, including the heart. Amongst other cytoprotective properties, ET was shown to scavenge ROS, decrease proinflammatory mediators, and chelate metal cations, including Fe2+, preventing them from partaking in redox activities, and may protect against mitochondrial damage and dysfunction. Plasma ET levels are also strongly correlated to a decreased risk of cardiovascular events in humans, suggesting a cardioprotective role. This evidence highlights ET's potential to counteract anthracycline cardiotoxicity. Methods and Findings: We investigated whether ET supplementation can protect against cardiac dysfunction in mice models of doxorubicin-induced cardiotoxicity and revealed that it had significant protective effects. Moreover, ET administration in a mouse breast cancer model did not exacerbate the growth of the tumor or interfere with the chemotherapeutic efficacy of doxorubicin. Conclusion: These results suggest that ET could be a viable co-therapy to alleviate the cardiotoxic effects of anthracyclines in the treatment of cancers.
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Nonalcoholic steatohepatitis (NASH) is the critical stage in the development of nonalcoholic fatty liver disease (NAFLD) from simple and reversible steatosis to irreversible cirrhosis and even hepatocellular carcinoma (HCC). Thus, the diagnosis of NASH is important for preventing the progress of NAFLD into a fatal condition. The oxidative enzyme myeloperoxidase (MPO), which is mostly produced by polymorphonuclear neutrophil granulocytes (NEU), has been identified as a key player in lipid peroxidation in inflamed tissues. Considering that the expression of MPO was much higher in NASH than in the nonalcoholic fatty liver (NAFL) with steatosis, we designed a nanoparticle platform based on ultrasmall iron oxide (USIO) nanoparticles to realize MPO-sensitive NASH diagnosis. After modification of USIO nanoparticles with amphiphilic poly(ethylene glycol) (PEG) and conjugation with 5-hydroxytryptamine (5HT), a physiological substrate for MPO, the final nanocomposite (USIO-DA-PEG-5HT) revealed MPO-mediated aggregation at the inflammatory site of NASH. Meanwhile, the intrinsic T1-weighted magnetic resonance (MR) signal of dispersed USIO-DA-PEG-5HT nanoparticles diminishes, while the T2-weighted MR signal is amplified owing to the aggregation effect. These USIO-DA-PEG-5HT nanoprobes offer great potential for improving NASH MR imaging diagnostic accuracy and sensitivity compared to existing molecular MR contrast agents with a single imaging modality.