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OBJECTIVE: The aim of this study was to explore the effect of simvastatin (Sim) on myocardial ischemia/reperfusion (I/R) injury in rats and to elucidate the possible underlying mechanism. Our findings might help to provide a certain reference for the clinical prevention and treatment of myocardial I/R injury. MATERIALS AND METHODS: A total of 60 male Sprague-Dawley (SD) rats were randomized into three groups using a random number table, including: Sham group (n=20), I/R group (n=20) and I/R + Sim group (n=20). The I/R injury model was successfully established in rats via ligation of the left anterior descending coronary artery (LAD), followed by reperfusion. Before operation, the rats in I/R + Sim group were administered with Sim at 10 mg/kg/d through oral gavage for 7 d. Cardiac ejection fraction (EF) (%) and fractional shortening (FS) (%) of rats in each group were detected using echocardiography. 2,3,5-triphenyltetrazolium chloride (TTC) staining was performed to measure the myocardial infarction (MI) area in each group. Collagen deposition in myocardial tissues of rats in each group was detected by Masson's trichrome staining. The apoptosis level of myocardial cells and fibroblasts in myocardial tissues of rats in each group were evaluated via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. The level of reactive oxygen species (ROS) in myocardial tissues of rats in each group was determined using fluorescent probes. Reverse Transcription-Polymerase Chain Reaction (RTPCR) was conducted to measure the expression levels of pro-inflammatory cytokines interleukin (IL)-1β and monocyte chemoattractant protein-1 (MCP-1) in myocardial tissues of rats in each group. Furthermore, the effects of Sim on the hedgehog signaling pathway-associated proteins were detected using Western blotting. RESULTS: Sim significantly alleviated I/R-induced cardiac dysfunction in rats and increased EF (%) and FS (%) (p<0.05). Meanwhile, it also evidently mitigated the MI caused by I/R and reduced the infarction area (p<0.05). According to the Masson's trichrome staining results, I/R + Sim group exhibited remarkably declined myocardial interstitial collagen deposition compared with I/R group (p<0.05). ROS-sensitive fluorescent staining showed that Sim notably reversed the increase of ROS expression and the decrease of myocardial oxidative stress induced by I/R (p<0.05). Finally, Western blotting results revealed that Sim dramatically restrained the protein expressions of sonic hedgehog (SHH), patched 1 (PTC1) and glioma-associated oncogene homolog 1 (GLI1) (p<0.05). CONCLUSIONS: Sim can significantly relieve myocardial I/R injury in rats. The possible underlying mechanism may be related to its inhibition on the hedgehog signaling pathway. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Autoimmune epilepsy is an under-recognized condition, and the mechanisms of antibody-mediated epileptogenesis are unknown. The N-methyl-D-aspartate (NMDA) receptor subunit 3 peptide B (NR3B) modulates Mg2+ sensitivity and Ca2+ mobilization of glutamate responses in the central nervous system (CNS). The levels of antibodies against NR3B (NR3B Ab's) in the cerebrospinal fluid (CSF) and the correlations between NR3B Ab's and cognitive comorbidities of epilepsy patients remain unclear. PATIENTS AND METHODS: CSF samples were collected from 36 patients with consecutive epilepsy and 17 healthy controls. The levels of NR3B Ab's in the CSF were measured by ELISA. The cognitive function was assessed by Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE). RESULTS: The results showed that the levels of NR3B Ab's were significantly higher in patients with epilepsy than those in the controls (p<0.01). Thirteen of 36 patients had higher levels of NR3B Ab's exceeding mean+ 2SD of all patients, and the scores of MMSE and MoCA of these 13 patients were significantly lower than the other 23 patients and controls (p<0.01; p<0.001). However, there were no significant differences in the scores of MMSE and MoCA between the 23 patients and the controls. Correlation analysis indicated a significant negative correlation between the levels of NR3B Ab's and the scores of MMSE (correlation coefficient: r=-0.543; p<0.01) or the scores of MoCA (correlation coefficient: r=-0.548; p<0.01). CONCLUSIONS: We suggest that some patients with epilepsy may have immune process after onset and the presence of NR3B Ab's may be associated with cognitive comorbidities in patients with epilepsy. [ABSTRACT FROM AUTHOR]

Radiofrequency thermo-ablation (RFTA) and trans-arterial chemoembolization (TACE) represent effective therapeutic strategies for cirrhotic patients with hepatocellular carcinoma (HCC). It has been proposed that body composition parameters, particularly skeletal muscle index (SMI), may predict outcomes in patients with HCC. However, only few studies investigated the role of visceral (VATI) and subcutaneous adipose tissue index (SATI) on patients' outcomes, and no data are available on the effect of their post-treatment changes in patients with HCC. to investigate the impact of early post-treatment changes in body composition parameters on the overall-survival (OS) of cirrhotic patients with HCC and on the probability of being transplanted. All cirrhotic patients with HCC treated for the first time with TACE or RFTA from 2012 to 2021 were retrospectively enrolled. Early changes of body composition (SMI, SATI and VATI) were extrapolated from abdominal CT scan performed before and one month after treatment and expressed as DELTA, following the formula: (one-month value- pre-procedure value)/ elapsed time. OS and probability of being transplanted were investigated with Fine-Gray multivariate competing risk analysis considering, respectively, LT and HCC progression outside the LT criteria (up-to-seven) as competitive risk events. 189 patients were enrolled, 132 undergoing TACE and 57 RFTA. In the multivariate analysis, across the entire population, the early decrease of VATI (DELTA-VATI negative) one month after treatment was associated to a increased risk of death (SHR=1.636; 95.0% CI=1.230-1.979; P=0.018), adjusting for age, MELDNa, Up-to-seven status and DELTA-SMI. In a sub-analysis, conducted considering only patients potentially eligible for LT, the early decrease in SMI (DELTA-SMI negative), but not in VATI was significantly associated to the need for LT (SHR=5.155; 95.0% CI=4.212-6.098; P<0.0001). early body composition parameters post-treatment changes are useful in identifying cirrhotic patients with HCC at increased risk of death or need of LT. [ABSTRACT FROM AUTHOR]

Liver transplant (LT) candidates are becoming older and more comorbid, with significant increase of metabolic associated fatty liver disease (MAFLD). The Charlson comorbidity index (CCI) is frequently used for risk stratification, even in the LT setting, but not for prediction of waitlist outcomes. We built a new risk score based on comorbidities, named Charlson Metabolic Comorbidity score (CMC-Score), adding within the CCI the clinical features of the metabolic syndrome not present. We then compared the new CMC-Score with the CCI regarding the ability to predict survival on the waiting list. All consecutive cirrhotic patients listed at our Liver Transplant Center from 2005 to 2019 were retrospectively analyzed. The CMC-Score was constructed by adding one point to the CCI for each clinical variable present among overweight/obesity, arterial hypertension, and dyslipidemia. Fine Gray multivariable competing risk analysis was employed to investigate risk factors for patients' death considering LT as competing event. 385 cirrhotic patients were enrolled, 45% had HCC and 70% had MAFLD. In the multivariate analysis, conducted considering the entire study population, the CMC-Score [SHR=1.260 (95.0%CI= 1.014-1.56); p=0.037], but not the CCI [SHR= 1.005 (95.0%CI=0.811 1.25); p=0.960], was the only statistically significant risk factor for death, adjusting for age, sex, MELDNa and presence of HCC. In a sub-analysis conducted in patients with HCC, the CMC-Score [SHR=1.604 (95.0%CI= 1.145-2.25); p=0.006], but not the CCI [SHR= 1.156 (95.0% CI= 0.815 1.64); p=0.42], was confirmed to be a relevant risk factor for death by adjusting for age, sex, MELDNa and the Up To Seven score of the HCC. The new CMC-Score is useful for identifying patients on the LT waiting list at increased risk of death. Further adjustments in the composition of the score and its validation should be made with multicenter and prospective studies. [ABSTRACT FROM AUTHOR]

Mn0·4Zn0·6NdxFe2-xO4/polyaniline (PANI) nanocomposites with magnetic properties were prepared by in situ polymerisation of aniline in the presence of Mn0·4Zn0·6NdxFe2-xO4 nanoparticles. The structure and morphologies of nanocomposites were characterised by X-ray diffraction, Fourier transform infrared (FTIR) spectroscopy and transmission electron microscopy (TEM). X-ray diffraction analysis shows that the size of Mn0·4Zn0·6NdxFe2-xO4 nanocomposites increases with the increase in the Nd doped amount. The optimum doped amount of Nd was 0·075, and the optimum calcination temperature was 850°C. The ferrite particles are well embedded in PANI chains. The FTIR results further prove that the Nd doped manganese-zinc-ferrite/PANI composites have been synthesised. Images (TEM) showed that the nanocomposites presented a spherical structure with a magnetic core of Mn0·4Zn0·6NdxFe2-xO4 and a conducting shell of PANI. The results showed that the electromagnetic properties of the Mn0·4Zn0·6NdxFe2-xO4/PANI composites were related to the mass ratio of PANI, the amount of Nd, the calcination temperature and the precipitation time. [ABSTRACT FROM AUTHOR]

OBJECTIVES: The aim of this study was to assess the long term effects of once-daily tacrolimus (OD-TAC) in a cohort of stable liver recipients converted from the twice daily tacrolimus (TD TAC), with a particular attention on the possible effects on renal function. PATIENTS AND METHODS: Between September 2008 and September 2010 conversion from TD-TAC to OD-TAC was proposed in adult stable liver transplant recipients who were followed as outpatients in our Transplant centre. Conversion from TC-TAC to OD-TAC was based on a 1 mg: 1 mg proportion. Tacrolimus through levels, laboratory parameters, metabolic disorders and any adverse events were evaluated at 1, 3, 6, 12 and 24 months after conversion. Renal function was evaluated using creatinine plasma levels and estimated glomerular filtration rate (GFR) derived from the Modification of Diet in Renal Disease (MDRD). Analysis of variance and t test for paired data were utilised for the comparison of the results obtained at the scheduled controls. RESULTS: Sixty-five patients were enrolled in the study (50 males, 15 females, mean age 59±8 years). Median time since liver transplant (LT) was 39 months (range: 6 to 83 months). All patients were followed for a minimum of 12 months. Ninety per cent of patients stabilized their blood levels within 45 days. Liver function, glucose and plasma lipids concentration and arterial blood pressure remained stable during the study. Renal function improved during the 24 months of follow-up. No adverse events or acute rejection episodes were recorded during the study. CONCLUSIONS: Considering the advantage on patient compliance, the equivalent efficacy and the adequate safety of OD-TAC formulation may represent a useful option in liver transplant patients, with a possible advantage on renal function. [ABSTRACT FROM AUTHOR]