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Myocardial Infarction (MI) is a leading cause of death worldwide. Metabolic modulation is a promising therapeutic approach to prevent adverse remodeling after MI. However, whether material‐derived cues can treat MI through metabolic regulation is mainly unexplored. Herein, a Cu2+ loaded casein microgel (CuCMG) aiming to rescue the pathological intramyocardial metabolism for MI amelioration is developed. Cu2+ is an important ion factor involved in metabolic pathways, and intracardiac copper drain is observed after MI. It is thus speculated that intramyocardial supplementation of Cu2+ can rescue myocardial metabolism. Casein, a milk‐derived protein, is screened out as Cu2+ carrier through molecular‐docking based on Cu2+ loading capacity and accessibility. CuCMGs notably attenuate MI‐induced cardiac dysfunction and maladaptive remodeling, accompanied by increased angiogenesis. The results from unbiased transcriptome profiling and oxidative phosphorylation analyses support the hypothesis that CuCMG prominently rescued the metabolic homeostasis of myocardium after MI. These findings enhance the understanding of the design and application of metabolic‐modulating biomaterials for ischemic cardiomyopathy therapy. [ABSTRACT FROM AUTHOR]

There is an ongoing global effort to advance emerging perovskite solar cells (PSCs), and many of these endeavours are focused on developing new compositions, processing methods and passivation strategies. In particular, the use of passivators to reduce the defects in perovskite materials has been demonstrated to be an effective approach for enhancing the photovoltaic performance and long-term stability of PSCs. Organic passivators have received increasing attention since the late 2010s as their structures and properties can readily be modified. First, this Review discusses the main types of defect in perovskite materials and reviews their properties. We examine the deleterious impact of defects on device efficiency and stability and highlight how defects facilitate extrinsic degradation pathways. Second, the proven use of different passivator designs to mitigate these negative effects is discussed, and possible defect passivation mechanisms are presented. Finally, we propose four specific directions for future research, which, in our opinion, will be crucial for unlocking the full potential of PSCs using the concept of defect passivation., (© 2023. Springer Nature Limited.)

Excess sodium intake is a leading but modifiable risk factor for mortality, with implications on hypertension, inflammation, cardiovascular disease, and chronic kidney disease (CKD). This review will focus mainly on the limitations of current measurement methods of sodium balance particularly in patients with CKD who have complex sodium physiology. The suboptimal accuracy of sodium intake and excretion measurement is seemingly more marked with the evolving understanding of tissue (skin and muscle) sodium. Tissue sodium represents an extrarenal influence on sodium homeostasis with demonstrated clinical associations of hypertension and inflammation. Measurement of tissue sodium has been largely unexplored in patients with CKD. Development and adoption of more comprehensive and dynamic assessment of body sodium balance is needed to better understand sodium physiology in the human body and explore therapeutic strategies to improve the clinical outcomes in the CKD population. [ABSTRACT FROM AUTHOR]

Maintenance hemodialysis (MHD) patients display significant nutritional abnormalities. Insulin is an anabolic hormone with direct effects on skeletal muscle (SM). We examined the anabolic actions of insulin, whole-body (WB), and SM protein turnover in 33 MHD patients and 17 participants without kidney disease using hyperinsulinemic-euglycemic-euaminoacidemic (dual) clamp. Gluteal muscle biopsies were obtained before and after the dual clamp. At baseline, WB protein synthesis and breakdown rates were similar in MHD patients. During dual clamp, controls had a higher increase in WB protein synthesis and a higher suppression of WB protein breakdown compared with MHD patients, resulting in statistically significantly more positive WB protein net balance [2.02 (interquartile range [IQR]: 1.79 and 2.36) vs. 1.68 (IQR: 1.46 and 1.91) mg·kg fat-free mass-1·min-1 for controls vs. for MHD patients, respectively, P < 0.001]. At baseline, SM protein synthesis and breakdown rates were higher in MHD patients versus controls, but SM net protein balance was similar between groups. During dual clamp, SM protein synthesis increased statistically significantly more in controls compared with MHD patients ( P = 0.03), whereas SM protein breakdown decreased comparably between groups. SM net protein balance was statistically significantly more positive in controls compared with MHD patients [67.3 (IQR: 46.4 and 97.1) vs. 15.4 (IQR: -83.7 and 64.7) μg·100 ml-1·min-1 for controls and MHD patients, respectively, P = 0.03]. Human SM biopsy showed a positive correlation between glucose and leucine disposal rates, phosphorylated AKT to AKT ratio, and muscle mitochondrial markers in controls but not in MHD patients. Diminished response to anabolic actions of insulin in the stimulated setting could lead to muscle wasting in MHD patients. [ABSTRACT FROM AUTHOR]

Wegener’s granulomatosis (WG) is characterized by necrotizing polyangiitis involving the respiratory tract and kidneys. It causes segmental necrotizing glomerulonephritis in the kidneys. In rare cases, a renal pseudotumor may be seen because of the granulomatous process. Association of WG with renal malignancy, however, is very uncommon. We report a case of a patient who presented several years after being treated for WG with malignant hypertension and an infiltrating mass in the right kidney. The histopathology of radical nephrectomy specimen showed presence of primitive neuroectodermal tumor (PNET). Association of renal cell carcinoma (RCC) with WG has been documented in a few cases, but PNET in such circumstances has not been reported. Long-term immunosuppressive treatment is a known risk factor in the development of malignancies, so it is proposed that the occurrence of RCC in WG may have been a side effect of cyclophosphamide treatment. It is not clear whether the same mechanism for PNET holds true in the present case. It is important to make a differential diagnosis between true malignancy and pseudotumors in WG as these entities cannot be distinguished based solely on imaging. We suggest a need to routinely screen the WG patients for increased risk of urologic malignancies. [ABSTRACT FROM AUTHOR]

Purpose: There are no robust data on hemoglobin (Hb), lactate dehydrogenase (LDH), and calcium variability for overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC) treated with vascular endothelial growth factor (VEGF)-targeted therapy. We aim to evaluate prognostic implications of Hb, LDH, and calcium variability and establish a novel risk stratification model in RCC patients receiving targeted therapies. Methods: We retrospectively studied an unselected cohort of patients with mRCC, who were treated with tyrosine kinase inhibitors. We assessed LDH variability, Ca variability, and Hb variability with various methods using standard deviation and fluctuation across thresholds. Kaplan-Meier and log-rank analyses were employed on OS and multivariate Cox proportional hazard model analyzed clinical parameters for their prognostic relevance. Results: A total of 59 patients intermediate-risk group according to the Memorial Sloan-Kettering Cancer Center with mRCC who had early progressed after first-line therapy with interferon-α were included in this retrospective single-center study conducted between February 2008 and December 2011. The mean Hb was 12.4 g/dl (min-max 9.1-15.2) throughout the study. Multivariable-adjusted Cox regression showed that patients in the consistently low-Hb group and patients in the low-amplitude and high-amplitude groups had a statistically significant increase in risk compared with patients who were consistently on target (HR 4.1; 95 % CI 1.3-12.9 and HR 2.9; 95 % CI 1.05-8.1 and HR 4.4; 95 % CI 1.7-11.1, respectively). On the other hand, the higher mean LDH (LDH more than 1 >upper limit of normal) was associated with OS. LDH variability and Ca variability were not associated with mortality. Conclusions: In patients with mRCC treated with VEGF-targeted therapy, Hb variability and mean LDH level might be associated with OS. This should be investigated prospectively. [ABSTRACT FROM AUTHOR]

Background: Fibroblast growth factor 23 (FGF23) is an important counterregulatory hormone for phosphate homeostasis. Since it has been reported that iron administration induces hypophosphatemic osteomalacia by triggering FGF23 synthesis, we hypothesized that iron administration might lead to a further increase in FGF23, resulting in alterations to Ca-P metabolism in a stage 5 CKD population. Methods: This cross-sectional study was performed in a single center, and involved 73 hemodialysis patients (47.7 ± 15.74 years old, 68.5 % men), 29 peritoneal dialysis patients (44.55 ± 15.05 years old, 62.1 % men), and 55 healthy (43.57 ± 14.36 years old, 55.6 % men) subjects. The dialysis group was subcategorized according to iron therapy administration into users and nonusers. Results: The median iFGF23 level was significantly higher in the dialysis population than in the healthy controls [88.050 (25.2-1038.3) pg/ml versus 46.95 (2.4-356) pg/ml ( p < 0.001)]. In the dialysis population, a significantly lower median iFGF23 level was observed in iron therapy users than in nonusers [87.6 (25.2-1038.3) versus 119 (51.6-1031); respectively, p = 0.045]. A significant negative association between iron administration and iFGF23 level was revealed by both univariate ( r = −0.237, p = 0.016) and multivariate ( β = −0.221, p = 0.032) analysis. No association was found between iFGF23 and serum ferritin and iron levels. Also, there was no association between iron therapy and serum phosphate level. Conclusion: In contrast to what is seen for the general population, this study showed that there was a negative relationship between iron administration and serum iFGF23 level in a dialysis population. We can therefore conclude that if high levels of FGF23 are harmful, iron therapy may have a beneficial effect on bone metabolism by reducing FGF23 levels in a dialysis population. [ABSTRACT FROM AUTHOR]

Introduction: The association between hyperuricemia and cardiovascular disease in hypertensive subjects is controversial. Attempts to elucidate the possible association between hyperuricemia and early atherosclerosis in hypertensive patients may provide alternative prevention or therapy targets for future cardiovascular events. Methods: A total of 67 hypertensive and 30 healthy subjects underwent B-mode ultrasonography to measure carotid intima media thickness (C-IMT). All biochemical analyses were assessed by local laboratories using standard laboratory methods. Results: C-IMT, serum uric acid (UA) levels, and mean arterial blood pressure (MBP) levels were significantly higher in hypertensive population compared to healthy subjects ( P<0.001). Among hypertensive subjects, high sensitivity C-reactive protein (hs-CRP), C-IMT, and proteinuria levels were significantly higher in hyperuricemic patients compared to normouricemic participants (for all, P<0.05). Age ( r=0.28, P=0.02), MBP ( r=0.34, P=0.04), hs-CRP ( r=0.58, P=0.006), proteinuria ( r=0.58, P=0.007), estimated glomerular filtration rate ( r=−0.35, P=0.02), and UA ( r=0.31, P=0.02) levels were significantly associated with C-IMT levels. Multiple linear regression analysis using C-IMT as a dependent variable showed that age ( beta=0.84, P=0.03) and UA levels ( beta=−0.87, P=0.02) were independently associated with C-IMT. Conclusion: Hyperuricemia is an independent predictor for early atherosclerosis in hypertensive subjects with normal renal function. Therefore, the optimal control of UA may provide further benefits in preventing atherosclerosis and hypertensive end-organ injury. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate the health-related quality of life (HRQOL) and mood conditions in familial Mediterranean fever (FMF) patients. Ninety FMF patients (F/M 60/30, median age 29) and 67 control subjects (F/M 46/21, median age 30) were included in this study. HRQOL was assessed with short form-36 (SF-36) and mood conditions were assessed with hospital anxiety depression scale (HADS). FMF patients had significantly lower mean scores on SF-36 physical components compared to the control group. However, mental components were comparable between groups. FMF patients were significantly more likely to have depression and anxiety compared to the control group [30 (33%) vs. 8 (12%), respectively, χ = 9.58, OR (95% CI) = 3.7 (1.5-8.7), p < 0.01 for depression and 48 (53%) and 11 (16%), respectively, χ = 22.31, OR (95% CI) = 5.8 (2.7-12.5), p < 0.001 for anxiety]. When frequency of anxious subjects was adjusted for the presence of concomitant depressive status as a confounding factor, the difference between the groups remained statistically significant [ χ = 11.86, OR (95% CI) = 5.4 (2.1-13.7), p < 0.01]. However, the difference of depression status between groups was not statistically significant when adjusted for the presence of concomitant anxiety status [ χ = 0.08, OR (95% CI) = 1.3 (0.5-3.8), p = 0.78] and FMF was found to be independently associated with only anxiety [OR (95% CI) = 7.1 (2.3-20.3)]. In addition, pure anxious FMF subgroup had significantly lower scores of mental health and mental component summary when compared to normal mood subgroup. In conclusion, FMF might adversely affect HRQOL. Depression and anxiety are more frequent in FMF patients than healthy subjects. [ABSTRACT FROM AUTHOR]

We investigated the association between familial Mediterranean fever (FMF) and osteoporosis (OP) in adult patients. Thirty-five attack-free FMF patients (28 females, 7 males; mean age 36.9 ± 5.7 years) were individually matched to control subjects on the basis of age (within 2 years) and sex. All patients were taking regular colchicine. Subjects having any condition that can cause decreased bone mineral density (BMD) were excluded from the study. BMD was measured at the spine and femur by dual X-ray absorptiometry (DXA). Data was given as the median (IQR). T scores of the spine were −0.700 (−1.097 to −0.262) and −0.450 (−0.830 to 0.112) in FMF patients and healthy controls, respectively ( p > 0.05). T scores of the femur neck were −0.900 (−1.480 to −0.570) and −0.430 (−1.472 to 0.247) in FMF patients and healthy controls, respectively ( p > 0.05). Total femur T scores were significantly lower in FMF patients than healthy controls (−0.780 [−1.222 to −0.085] vs. −0.100 [−0.765 to 0.537], respectively, p = 0.021). Total femur T scores were significantly decreased in adult patients with FMF. Ongoing subclinical inflammation may be associated with decreased bone mineral content in those patients. [ABSTRACT FROM AUTHOR]

Development of uroepithelial tumors after cyclophosphamide and azathioprine therapy in Wegener’s granulomatosis (WG) have been reported in the literature but renal cell carcinoma (RCC), rarely. RCC associated with WG has been previously reported in a few cases. Most of them have simultaneous diseases. Here, we report a case, which developed RCC 8 years after initiation of WG. Long-term immunosuppressive treatment is a risk factor for the development of malignancies; it should be suggested that RCC in our patient might be due to immunosuppressive therapy. [ABSTRACT FROM AUTHOR]