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Nano-micro Letters Dec 2023The ultrasmall gold nanoparticles (AuNPs), serving as a bridge between small molecules and traditional inorganic nanoparticles, create significant opportunities to... (Review)
Review
UNLABELLED
The ultrasmall gold nanoparticles (AuNPs), serving as a bridge between small molecules and traditional inorganic nanoparticles, create significant opportunities to address many challenges in the health field. This review discusses the recent advances in the biological interactions and imaging of ultrasmall AuNPs. The challenges and the future development directions of the ultrasmall AuNPs are presented.
ABSTRACT
Ultrasmall gold nanoparticles (AuNPs) typically includes atomically precise gold nanoclusters (AuNCs) and AuNPs with a core size below 3 nm. Serving as a bridge between small molecules and traditional inorganic nanoparticles, the ultrasmall AuNPs show the unique advantages of both small molecules (e.g., rapid distribution, renal clearance, low non-specific organ accumulation) and nanoparticles (e.g., long blood circulation and enhanced permeability and retention effect). The emergence of ultrasmall AuNPs creates significant opportunities to address many challenges in the health field including disease diagnosis, monitoring and treatment. Since the nano–bio interaction dictates the overall biological applications of the ultrasmall AuNPs, this review elucidates the recent advances in the biological interactions and imaging of ultrasmall AuNPs. We begin with the introduction of the factors that influence the cellular interactions of ultrasmall AuNPs. We then discuss the organ interactions, especially focus on the interactions of the liver and kidneys. We further present the recent advances in the tumor interactions of ultrasmall AuNPs. In addition, the imaging performance of the ultrasmall AuNPs is summarized and discussed. Finally, we summarize this review and provide some perspective on the future research direction of the ultrasmall AuNPs, aiming to accelerate their clinical translation. [Image: see text]
PubMed: 38047998
DOI: 10.1007/s40820-023-01266-4 -
Circulation Aug 2023Although heart transplantation is the preferred therapy for appropriate patients with advanced heart failure, the presence of concomitant renal or hepatic dysfunction... (Review)
Review
Dual-Organ Transplantation: Indications, Evaluation, and Outcomes for Heart-Kidney and Heart-Liver Transplantation: A Scientific Statement From the American Heart Association.
Although heart transplantation is the preferred therapy for appropriate patients with advanced heart failure, the presence of concomitant renal or hepatic dysfunction can pose a barrier to isolated heart transplantation. Because donor organ supply limits the availability of organ transplantation, appropriate allocation of this scarce resource is essential; thus, clear guidance for simultaneous heart-kidney transplantation and simultaneous heart-liver transplantation is urgently required. The purposes of this scientific statement are (1) to describe the impact of pretransplantation renal and hepatic dysfunction on posttransplantation outcomes; (2) to discuss the assessment of pretransplantation renal and hepatic dysfunction; (3) to provide an approach to patient selection for simultaneous heart-kidney transplantation and simultaneous heart-liver transplantation and posttransplantation management; and (4) to explore the ethics of multiorgan transplantation.
PubMed: 37439224
DOI: 10.1161/CIR.0000000000001155 -
La Radiologia Medica Sep 2023Glymphatic system maintains brain fluid circulation via active transportation of astrocytic aquaporin-4 in perivascular space. The diffusion tensor imaging analysis...
OBJECTIVES
Glymphatic system maintains brain fluid circulation via active transportation of astrocytic aquaporin-4 in perivascular space. The diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) is an established method measuring perivascular glymphatic activity, but comprehensive investigations into its influential factors are lacking.
METHODS
Community-dwelling older adults underwent brain MRI scans, neuropsychiatric, and multi-domain assessments. Blood biomarker tests included glial fibrillary acidic protein (GFAP) for astrocyte injury.
RESULTS
In 71 enrolled participants, the DTI-ALPS index was associated with modifiable factors, including lipid profile (high-density lipoprotein, r = 0.396; very-low-density lipoprotein, r = - 0.342), glucose intolerance (diabetes mellitus, standardized mean difference (SMD) = 0.7662; glycated hemoglobin, r = - 0.324), obesity (body mass index, r = - 0.295; waist, r = - 0.455), metabolic syndrome (SMD = - 0.6068), cigarette-smoking (SMD = - 0.6292), and renal clearance (creatinine, r = - 0.387; blood urea nitrogen, r = - 0.303). Unmodifiable associative factors of DTI-ALPS were age (r = - 0.434) and sex (SMD = 1.0769) (all p < 0.05). A correlation of DTI-ALPS and blood GFAP was noticed (r = - 0.201, one-tailed t-test for the assumption that astrocytic injury impaired glymphatic activity, p = 0.046). Their cognitive correlations diverged, domain-specific for DTI-ALPS (Facial Memory Test, r = 0.272, p = 0.022) but global cognition-related for blood GFAP (MoCA, r = - 0.264, p = 0.026; ADAS-cog, r = 0.304, p = 0.010).
CONCLUSION
This correlation analysis revealed multiple modifiable and unmodifiable association factors to the glymphatic image marker. The DTI-ALPS index correlated with various metabolic factors that are known to increase the risk of vascular diseases such as atherosclerosis. Furthermore, the DTI-ALPS index was associated with renal indices, and this connection might be a link of water regulation between the two systems. In addition, the astrocytic biomarker, plasma GFAP, might be a potential marker of the glymphatic system; however, more research is needed to confirm its effectiveness.
Topics: Humans; Aged; Glymphatic System; Diffusion Tensor Imaging; Astrocytes; Risk Factors; Brain
PubMed: 37462887
DOI: 10.1007/s11547-023-01675-w -
Journal of the American Heart... Jul 2023Background Fontan circulation is associated with kidney injury and dysfunction, often unappreciated until Fontan circulatory failure. We hypothesized that cystatin...
Background Fontan circulation is associated with kidney injury and dysfunction, often unappreciated until Fontan circulatory failure. We hypothesized that cystatin C-estimated glomerular filtration rate (eGFR) would identify chronic kidney disease more frequently and that urine kidney injury biomarkers would be higher with declining Fontan physiological features. Methods and Results We enrolled 100 ambulatory individuals. Blood and urinary laboratory measurements were compared with demographics and clinically obtained data. Different eGFR equations were used for individuals aged ≥19 years and <19 years. Chronic kidney disease was defined as eGFR <90 mL/min per 1.73 m. Median (25th-75th percentile) age was 19 (14-26) years, and 43% were female patients. Cystatin C eGFR detected chronic kidney disease (37%) in more patients than creatinine eGFR (11%). Cystatin C eGFR was positively associated, and skeletal muscle mass was negatively associated, with creatinine eGFR in both univariate (cystatin C eGFR β=0.44±0.12, =0.0006; skeletal muscle mass β=-0.72±0.32, =0.03) and multivariable analysis (cystatin C eGFR β=0.43±0.12, =0.0005; skeletal muscle mass β=-0.69±0.29, =0.02). Urine neutrophil gelatinase-associated lipocalin concentration correlated with Fontan pressure (=0.28; =0.04), ventricular end-diastolic pressure (=0.28; =0.04), and body fat mass (=0.26; =0.03). Conclusions Cystatin C eGFR identified more kidney dysfunction, likely attributable to creatinine eGFR being confounded by skeletal muscle mass. Elevated urine neutrophil gelatinase-associated lipocalin was associated with worse Fontan hemodynamics and higher percentage body fat, suggesting that higher venous pressure and higher adiposity are associated with ongoing kidney injury.
Topics: Humans; Female; Male; Lipocalin-2; Cystatin C; Creatinine; Fontan Procedure; Kidney; Biomarkers; Renal Insufficiency, Chronic; Glomerular Filtration Rate
PubMed: 37345835
DOI: 10.1161/JAHA.122.029130 -
American Journal of Physiology. Renal... Dec 2023Kidney organoids are three-dimensional structures generated from pluripotent stem cells (PSCs) that are capable of recapitulating the major structures of mammalian... (Review)
Review
Kidney organoids are three-dimensional structures generated from pluripotent stem cells (PSCs) that are capable of recapitulating the major structures of mammalian kidneys. As this technology is expected to be a promising tool for studying renal biology, drug discovery, and regenerative medicine, the functional capacity of kidney organoids has emerged as a critical question in the field. Kidney organoids produced using several protocols harbor key structures of native kidneys. Here, we review the current state, recent advances, and future challenges in the functional characterization of kidney organoids, strategies to accelerate and enhance kidney organoid functions, and access to PSC resources to advance organoid research. The strategies to construct physiologically relevant kidney organoids include the use of organ-on-a-chip technologies that integrate fluid circulation and improve organoid maturation. These approaches result in increased expression of the major tubular transporters and elements of mechanosensory signaling pathways suggestive of improved functionality. Nevertheless, continuous efforts remain crucial to create kidney tissue that more faithfully replicates physiological conditions for future applications in kidney regeneration medicine and their ethical use in patient care. Kidney organoids are three-dimensional structures derived from stem cells, mimicking the major components of mammalian kidneys. Although they show great promise, their functional capacity has become a critical question. This review explores the advancements and challenges in evaluating and enhancing kidney organoid function, including the use of organ-on-chip technologies, multiomics data, and in vivo transplantation. Integrating these approaches to further enhance their physiological relevance will continue to advance disease modeling and regenerative medicine applications.
Topics: Animals; Humans; Kidney; Regeneration; Nephrons; Pluripotent Stem Cells; Organoids; Mammals
PubMed: 37767571
DOI: 10.1152/ajprenal.00166.2023 -
Perfusion Apr 2024Cardiac surgery on cardiopulmonary bypass (CPB) is associated with postoperative renal dysfunction, one of the most common complications of this surgical cohort. Acute... (Review)
Review
Cardiac surgery on cardiopulmonary bypass (CPB) is associated with postoperative renal dysfunction, one of the most common complications of this surgical cohort. Acute kidney injury (AKI) is associated with increased short-term morbidity and mortality and has been the focus of much research. There is increasing recognition of the role of AKI as the key pathophysiological state leading to the disease entities acute and chronic kidney disease (AKD and CKD). In this narrative review, we will consider the epidemiology of renal dysfunction after cardiac surgery on CPB and the clinical manifestations across the spectrum of disease. We will discuss the transition between different states of injury and dysfunction, and, importantly, the relevance to clinicians. The specific facets of kidney injury on extracorporeal circulation will be described and the current evidence evaluated for the use of perfusion-based techniques to reduce the incidence and mitigate the complications of renal dysfunction after cardiac surgery.
Topics: Humans; Cardiopulmonary Bypass; Postoperative Complications; Cardiac Surgical Procedures; Acute Kidney Injury; Kidney; Risk Factors; Retrospective Studies
PubMed: 36794518
DOI: 10.1177/02676591231157055 -
Journal of the American College of... Nov 2023The SCORED (Effect of Sotagliflozin on Cardiovascular and Renal Events in Patients with Type 2 Diabetes and Moderate Renal Impairment Who Are at Cardiovascular Risk) and...
BACKGROUND
The SCORED (Effect of Sotagliflozin on Cardiovascular and Renal Events in Patients with Type 2 Diabetes and Moderate Renal Impairment Who Are at Cardiovascular Risk) and SOLOIST-WHF (Effect of Sotagliflozin on Cardiovascular Events in Patients with Type 2 Diabetes Post Worsening Heart Failure) trials demonstrated that sotagliflozin, an SGLT1 and SGLT2 inhibitor, improves outcomes in individuals with type 2 diabetes who have heart failure (HF) or kidney disease.
OBJECTIVES
We assessed the efficacy of sotagliflozin on HF clinical outcomes in individuals with differing baseline glycosylated hemoglobin (HbA1c) levels.
METHODS
We included all adults from SCORED and SOLOIST-WHF. The primary outcome was a composite of cardiovascular death, hospitalizations for HF, and urgent visits for HF. The efficacy of sotagliflozin compared with placebo was evaluated by baseline HbA1c using competing-risk marginal proportional hazards models.
RESULTS
We identified 11,744 adults. Individuals with HbA1c ≤7.5% experienced the primary outcome at a lower rate in the sotagliflozin group (11.2 per 100 person-years) than the placebo group (15.5 per 100 person-years) (HR: 0.73; 95% CI: 0.57-0.93). Similarly, individuals with HbA1c of 7.6% to 9.0% experienced the primary outcome at a lower rate in the sotagliflozin group (7.3 per 100 person-years) than the placebo group (9.4 per 100 person-years) (HR: 0.77; 95% CI: 0.63-0.96). These findings were also consistent among individuals with HbA1c >9.0%, with a primary outcome rate in the sotagliflozin group (7.8 per 100 person-years) that was lower than the placebo group (11.6 per 100 person-years) (HR: 0.65; 95% CI: 0.50-0.84). The efficacy of sotagliflozin was consistent by baseline HbA1c level (P for interaction = 0.58).
CONCLUSIONS
In individuals with type 2 diabetes and either HF or kidney disease, sotagliflozin reduced HF outcomes irrespective of baseline HbA1c.
Topics: Humans; Adult; Glycated Hemoglobin; Diabetes Mellitus, Type 2; Diabetes Mellitus, Type 1; Kidney Diseases; Heart Failure
PubMed: 37914514
DOI: 10.1016/j.jacc.2023.08.050 -
Frontiers in Cardiovascular Medicine 2023Massive pulmonary embolism (MPE) carries significant 30-day mortality and is characterized by acute right ventricular failure, hypotension, and hypoxia, leading to... (Review)
Review
Massive pulmonary embolism (MPE) carries significant 30-day mortality and is characterized by acute right ventricular failure, hypotension, and hypoxia, leading to cardiovascular collapse and cardiac arrest. Given the continued high mortality associated with MPE, there has been ongoing interest in utilizing extracorporeal membrane oxygenation (ECMO) to provide oxygenation support to improve hypoxia and offload the right ventricular (RV) pressure in the belief that rapid reduction of hypoxia and RV pressure will improve outcomes. Two modalities can be employed: Veno-arterial-ECMO is a reliable process to decrease RV overload and improve RV function, thus allowing for hemodynamic stability and restoration of tissue oxygenation. Veno-venous ECMO can support oxygenation but is not designed to help circulation. Several societal guidelines now suggest using ECMO in MPE with interventional therapy. There are three strategies for ECMO utilization in MPE: bridge to definitive interventional therapy, sole therapy, and recovery after interventional treatment. The use of ECMO in MPE has been associated with lower mortality in registry reviews, but there has been no significant difference in outcomes between patients treated with and without ECMO in meta-analyses. Considerable heterogeneity in studies is a significant weakness of the available literature. Applying ECMO is also associated with substantial multisystem morbidity due to a systemic inflammatory response, hemorrhagic stroke, renal dysfunction, and bleeding, which must be factored into the outcomes. The application of ECMO in MPE should be combined with an aggressive pulmonary interventional program and should strictly adhere to the current selection criteria.
PubMed: 38179509
DOI: 10.3389/fcvm.2023.1298686 -
Nutrients May 2024Vitamin D is a crucial micronutrient, critical to human health, and influences many physiological processes. Oral and skin-derived vitamin D is hydroxylated to form... (Review)
Review
Vitamin D is a crucial micronutrient, critical to human health, and influences many physiological processes. Oral and skin-derived vitamin D is hydroxylated to form calcifediol (25(OH)D) in the liver, then to 1,25(OH)D (calcitriol) in the kidney. Alongside the parathyroid hormone, calcitriol regulates neuro-musculoskeletal activities by tightly controlling blood-ionized calcium concentrations through intestinal calcium absorption, renal tubular reabsorption, and skeletal mineralization. Beyond its classical roles, evidence underscores the impact of vitamin D on the prevention and reduction of the severity of diverse conditions such as cardiovascular and metabolic diseases, autoimmune disorders, infection, and cancer. Peripheral target cells, like immune cells, obtain vitamin D and 25(OH)D through concentration-dependent diffusion from the circulation. Calcitriol is synthesized intracellularly in these cells from these precursors, which is crucial for their protective physiological actions. Its deficiency exacerbates inflammation, oxidative stress, and increased susceptibility to metabolic disorders and infections; deficiency also causes premature deaths. Thus, maintaining optimal serum levels above 40 ng/mL is vital for health and disease prevention. However, achieving it requires several times more than the government's recommended vitamin D doses. Despite extensive published research, recommended daily intake and therapeutic serum 25(OH)D concentrations have lagged and are outdated, preventing people from benefiting. Evidence suggests that maintaining the 25(OH)D concentrations above 40 ng/mL with a range of 40-80 ng/mL in the population is optimal for disease prevention and reducing morbidities and mortality without adverse effects. The recommendation for individuals is to maintain serum 25(OH)D concentrations above 50 ng/mL (125 nmol/L) for optimal clinical outcomes. Insights from metabolomics, transcriptomics, and epigenetics offer promise for better clinical outcomes from vitamin D sufficiency. Given its broader positive impact on human health with minimal cost and little adverse effects, proactively integrating vitamin D assessment and supplementation into clinical practice promises significant benefits, including reduced healthcare costs. This review synthesized recent novel findings related to the physiology of vitamin D that have significant implications for disease prevention.
Topics: Humans; Vitamin D; Vitamin D Deficiency; Dietary Supplements; Cardiovascular Diseases
PubMed: 38892599
DOI: 10.3390/nu16111666 -
Critical Care (London, England) Sep 2023We examined the risk of severe life-threatening morbidity in pregnant patients with Covid-19 infection.
BACKGROUND
We examined the risk of severe life-threatening morbidity in pregnant patients with Covid-19 infection.
METHODS
We conducted a population-based study of 162,576 pregnancies between March 2020 and March 2022 in Quebec, Canada. The main exposure was Covid-19 infection, including the severity, period of infection (antepartum, peripartum), and circulating variant (wildtype, alpha, delta, omicron). The outcome was severe maternal morbidity during pregnancy up to 42 days postpartum. We estimated risk ratios (RR) and 95% confidence intervals (CI) for the association between Covid-19 infection and severe maternal morbidity using adjusted log-binomial regression models.
RESULTS
Covid-19 infection was associated with twice the risk of severe maternal morbidity compared with no infection (RR 2.02, 95% CI 1.76-2.31). Risks were elevated for acute renal failure (RR 3.01, 95% CI 1.79-5.06), embolism, shock, sepsis, and disseminated intravascular coagulation (RR 1.35, 95% CI 0.95-1.93), and severe hemorrhage (RR 1.49, 95% CI 1.09-2.04). Severe antepartum (RR 13.60, 95% CI 10.72-17.26) and peripartum infections (RR 20.93, 95% CI 17.11-25.60) were strongly associated with severe maternal morbidity. Mild antepartum infections also increased the risk, but to a lesser magnitude (RR 3.43, 95% CI 2.42-4.86). Risk of severe maternal morbidity was around 3 times greater during circulation of wildtype and the alpha and delta variants, but only 1.2 times greater during omicron.
CONCLUSIONS
Covid-19 infection during pregnancy increases risk of life-threatening maternal morbidity, including renal, embolic, and hemorrhagic complications. Severe Covid-19 infection with any variant in the antepartum or peripartum periods all increase the risk of severe maternal morbidity.
Topics: Female; Pregnancy; Humans; COVID-19; SARS-CoV-2; Canada; Disseminated Intravascular Coagulation; Pregnancy Complications, Infectious
PubMed: 37670329
DOI: 10.1186/s13054-023-04584-6