Post translational modifications of connexin 43 in ventricular arrhythmias after myocardial infarction.

Ventricular arrhythmias are the leading cause of sudden cardiac death in patients after myocardial infarction (MI). Connexin43 (Cx43) is the most important gap junction channel-forming protein in cardiomyocytes. Dysfunction of Cx43 contributes to impaired myocardial conduction and the development of ventricular arrhythmias. Following an MI, Cx43 undergoes structural remodeling, including expression abnormalities, and redistribution. These alterations detrimentally affect intercellular communication and electrical conduction within the myocardium, thereby increasing the susceptibility to post-infarction ventricular arrhythmias. Emerging evidence suggests that post-translational modifications play essential roles in Cx43 regulation after MI. Therefore, Cx43-targeted management has the potential to be a promising protective strategy for the prevention and treatment of post infarction ventricular arrhythmias. In this article, we primarily reviewed the regulatory mechanisms of Cx43 mediated post-translational modifications on post-infarction ventricular arrhythmias. Furthermore, Cx43-targeted therapy have also been discussed, providing insights into an innovative treatment strategy for ventricular arrhythmias after MI.

Development of a label-free photoelectrochemical immunosensor for novel astrovirus detection.

Since 2017, an infectious goose gout disease characterized by urate precipitation in viscera, mainly caused by novel goose astrovirus (GoAstV) infection, has emerged in the main goose-producing region of China. The current challenge in managing goose gout disease is largely due to the absence of a rapid and efficient detection method for the GoAstV pathogen. Notably, the potential application of immunosensors in detecting GoAstV has not yet been explored. Herein, a label-free PEC immunosensor was fabricated by using purchased TiO2 as the photoactive material and antibody against GoAstV P2 proteins as the specific recognition element. First, we successfully expressed the capsid spike domain P2 protein of ORF2 from GoAstV CHSH01 by using the pET prokaryotic expression system. Meanwhile, the polyclonal antibody against GoAstV capsid P2 protein was produced by purified protein. To our knowledge, this is the first establishment and preliminary application of the label-free photoelectrochemical immunosensor method in the detection of AstV. The PEC immunosensor had a linear range of 1.83 fg mL-1 to 3.02 ng mL-1, and the limit of detection (LOD) was as low as 0.61 fg mL-1. This immunosensor exhibited high sensitivity, great specificity, and good stability in detecting GoAstV P2 proteins. To evaluate the practical application of the immunosensor in real-world sample detection, allantoic fluid from goose embryos was collected as test samples. The results indicated that of the eight positive samples, one false negative result was detected, while both negative samples were accurately detected, suggesting that the constructed PEC immunosensor had good applicability and practical application value, providing a platform for the qualitative detection of GoAstV.

Calcineurin/NFATc3 pathway mediates myocardial fibrosis in diabetes by impairing enhancer of zeste homolog 2 of cardiac fibroblasts.

BACKGROUND: Diabetes is associated with myocardial fibrosis, while the underlying mechanisms remain elusive. The aim of this study is to investigate the underlying role of calcineurin/nuclear factor of activated T cell 3 (CaN/NFATc3) pathway and the Enhancer of zeste homolog 2 (EZH2) in diabetes-related myocardial fibrosis. METHODS: Streptozotocin (STZ)-injected diabetic rats were randomized to two groups: the controlled glucose (Con) group and the diabetes mellitus (DM) group. Eight weeks later, transthoracic echocardiography was used for cardiac function evaluation, and myocardial fibrosis was visualized by Masson trichrome staining. The primary neonatal rat cardiac fibroblasts were cultured with high-glucose medium with or without cyclosporine A or GSK126. The expression of proteins involved in the pathway was examined by western blotting. The nuclear translocation of target proteins was assessed by immunofluorescence. RESULTS: The results indicated that high glucose treatment increased the expression of CaN, NFATc3, EZH2 and trimethylates lysine 27 on histone 3 (H3K27me3) in vitro and in vivo. The inhibition of the CaN/NFATc3 pathway alleviated myocardial fibrosis. Notably, inhibition of CaN can inhibit the nuclear translocation of NFATc3, and the expression of EZH2 and H3K27me3 protein induced by high glucose. Moreover, treatment with GSK126 also ameliorated myocardial fibrosis. CONCLUSION: Diabetes can possibly promote myocardial fibrosis by activating of CaN/NFATc3/EZH2 pathway.

Berberine Regulates GPX4 to Inhibit Ferroptosis of Islet ß Cells.

Ferroptosis, as a kind of non-apoptotic cell death, is involved in the pathogenesis of type 1 diabetes mellitus (T1DM). Islet B cells mainly produce insulin that is used to treat diabetes. Berberine (BBR) can ameliorate type 2 diabetes and insulin resistance in many ways. However, a few clues concerning the mechanism of BBR regulating ferroptosis of islet ß cells in T1DM have been detected so far. We measured the effects of BBR and GPX4 on islet ß cell viability and proliferation by MTT and colony formation assays. Western blot and qRT-PCR were utilized to examine GPX4 expression in islet ß cells with distinct treatments. The influence of BBR and GPX4 on ferroptosis of islet ß cells was investigated by evaluating the content of Fe2+ and reactive oxygen species (ROS) in cells. The mechanism of BBR targeting GPX4 to inhibit ferroptosis of islet ß cells was further revealed by the rescue experiment. Our results showed that BBR and overexpression of GPX4 could notably accelerate cell viability and the proliferative abilities of islet ß cells. Moreover, BBR stimulated GPX4 expression to reduce the content of Fe2+ and ROS, thereby repressing the ferroptosis of islet ß cells, which functioned similarly as ferroptosis inhibitor Fer-1. In conclusion, BBR suppressed ferroptosis of islet ß cells via promoting GPX4 expression, providing new insights into the mechanism of BBR for islet ß cells.

The toxic effect of bisphenol AF and nanoplastic coexposure in parental and offspring generation zebrafish.

Microplastics (MPs) and bisphenol AF (BPAF) are two environmental pollutants that usually coexist in the natural environment. Studies of MPs or BPAF have gradually increased in recent years, but few studies have focused on the combination toxic effects. In this study, the subchronic model of adult zebrafish was exposed to 1 mg/L nanolevel microplastics and 200 µg/L BPAF for 45 days; the parental zebrafish were spawning every 3 days during exposure, and the effects of continuous poisoning were examined on the offspring after 1-9 spawns. The results showed that single BPAF exposure or BPAF and nanoplastic coexposure can both decrease the number of eggs laid and the locomotor behavior of parental zebrafish and impact the hatching rate, mortality, body length and locomotor behavior of offspring zebrafish, especially in 7-9 spawn. BPAF were accumulated in parental zebrafish intestinal in 334.62 ng/g in BPAF group and 594.52 ng/g in nm+BPAF group, and accumulated in whole offspring zebrafish for 281.6 ng/g in BPAF group and 321.46 ng/g in nm+BPAF group. Neurodevelopmental, inflammation, apoptosis and oxidative stress-related genes were also significantly increased after 7-9 spawn. In addition, the exacerbated accumulation in the BPAF+nm group in parental and offspring zebrafish may be the reason for the accelerated toxic effect in the present research. In this study, we investigated the combined effects of nanoplastics and BPAF on parental and offspring zebrafish in the aquatic environment to identify the accumulative toxic effects and provide new experimental support for assessing the effects of coexposure on aquatic organisms.

Neurodevelopmental Toxicity of Emamectin Benzoate to the Early Life Stage of Zebrafish Larvae (Danio rerio).

Emamectin benzoate (EMB) is a widely used pesticide and feed additive in agriculture and aquaculture. It easily enters the aquatic environment through various pathways, thus causing adverse effects on aquatic organisms. However, there are no systematic studies regarding the effects of EMB on the developmental neurotoxicity of aquatic organisms. Therefore, the aim of this study was to evaluate the neurotoxic effects and mechanisms of EMB at different concentrations (0.1, 0.25, 0.5, 1, 2, 4 and 8 µg/mL) using zebrafish as a model. The results showed that EMB significantly inhibited the hatching rate, spontaneous movement, body length, and swim bladder development of zebrafish embryos, as well as significantly increased the malformation rate of zebrafish larvae. In addition, EMB adversely affected the axon length of motor neurons in Tg (hb9: eGFP) zebrafish and central nervous system (CNS) neurons in Tg (HuC: eGFP) zebrafish and significantly inhibited the locomotor behavior of zebrafish larvae. Meanwhile, EMB induced oxidative damage and was accompanied by increasing reactive oxygen species in the brains of zebrafish larvae. In addition, gene expression involvement in oxidative stress-related (cat, sod and Cu/Zn-sod), GABA neural pathway-related (gat1, gabra1, gad1b, abat and glsa), neurodevelopmental-related (syn2a, gfap, elavl3, shha, gap43 and Nrd) and swim bladder development-related (foxa3, pbxla, mnx1, has2 and elovlla) genes was significantly affected by EMB exposure. In conclusion, our study shows that exposure to EMB during the early life stages of zebrafish significantly increases oxidative damage and inhibits early central neuronal development, motor neuron axon growth and swim bladder development, ultimately leading to neurobehavioral changes in juvenile zebrafish.

Endocrine, genetic, and microbiome nexus of obesity and potential role of postbiotics: a narrative review.

Obesity is a public health crisis, presenting a huge burden on health care and the economic system in both developed and developing countries. According to the WHO's latest report on obesity, 39% of adults of age 18 and above are obese, with an increase of 18% compared to the last few decades. Metabolic energy imbalance due to contemporary lifestyle, changes in gut microbiota, hormonal imbalance, inherent genetics, and epigenetics is a major contributory factor to this crisis. Multiple studies have shown that probiotics and their metabolites (postbiotics) supplementation have an effect on obesity-related effects in vitro, in vivo, and in human clinical investigations. Postbiotics such as the SCFAs suppress obesity by regulating metabolic hormones such as GLP-1, and PPY thus reducing feed intake and suppressing appetite. Furthermore, muramyl di-peptides, bacteriocins, and LPS have been tested against obesity and yielded promising results in both human and mice studies. These insights provide an overview of targetable pharmacological sites and explore new opportunities for the safer use of postbiotics against obesity in the future.

Developmental and Reproductive Impacts of Four Bisphenols in Daphnia magna.

Bisphenol A (BPA) is a typical endocrine-disrupting chemical (EDC) used worldwide. Considering its adverse effects, BPA has been banned or strictly restricted in some nations, and many analogs have been introduced to the market. In this study, we selected three representative substitutes, BPS, BPF, and BPAF, along with BPA, to assess the developmental and reproductive effects on Daphnia magna. The F0 generation was exposed to bisphenols (BPs) at an environmentally relevant concentration (100 µg/L) for 21 d; then the embryo spawn at day 21 was collected. Behavior traits, the activity of antioxidant enzymes, and gene transcription were evaluated at three developmental stages (days 7, 14, and 21). Notably, body length, heart rate, and thoracic limb beating were significantly decreased, and D. magna behaved more sluggishly in the exposed group. Moreover, exposure to BPs significantly increased the antioxidant enzymatic activities, which indicated that BPs activated the antioxidant defense system. Additionally, gene expression indicated intergenerational effects in larvae, particularly in the BPAF group. In conclusion, BPA analogs such as BPF and BPAF showed similar or stronger reproductive and developmental toxicity than BPA in D. magna. These findings collectively deepen our understanding of the toxicity of BPA analogs and provide empirical evidence for screening safe alternatives to BPA.

FGF21/adiponectin ratio predicts deterioration in glycemia: a 4.6-year prospective study in China.

BACKGROUND: The fibroblast growth factor (FGF) 21-adiponectin pathway is involved in the regulation of insulin resistance. However, the relationship between the FGF21-adiponectin pathway and type 2 diabetes in humans is unclear. Here, we investigated the association of FGF21/adiponectin ratio with deterioration in glycemia in a prospective cohort study. METHODS: We studied 6361 subjects recruited from the prospective Shanghai Nicheng Cohort Study in China. The association between baseline FGF21/adiponectin ratio and new-onset diabetes and incident prediabetes was evaluated using multiple logistic regression analysis. RESULTS: At baseline, FGF21/adiponectin ratio levels increased progressively with the deterioration in glycemic control from normal glucose tolerance to prediabetes and diabetes (p for trend < 0.001). Over a median follow-up of 4.6 years, 195 subjects developed new-onset diabetes and 351 subjects developed incident prediabetes. Elevated baseline FGF21/adiponectin ratio was a significant predictor of new-onset diabetes independent of traditional risk factors, especially in subjects with prediabetes (odds ratio, 1.367; p = 0.001). Moreover, FGF21/adiponectin ratio predicted incident prediabetes (odds ratio, 1.185; p = 0.021) while neither FGF21 nor adiponectin were independent predictors of incident prediabetes (both p > 0.05). Furthermore, net reclassification improvement and integrated discrimination improvement analyses showed that FGF21/adiponectin ratio provided a better performance in diabetes risk prediction than the use of FGF21 or adiponectin alone. CONCLUSIONS: FGF21/adiponectin ratio independently predicted the onset of prediabetes and diabetes, with the potential to be a useful biomarker of deterioration in glycemia.

Modulation of SK Channels: Insight Into Therapeutics of Atrial Fibrillation.

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia in the world. Although much technological progress in the treatment of AF has been made, there is an urgent need for better treatment of AF due to its high rates of morbidity and mortality. The anti-arrhythmic drugs currently approved for marketing have significant limitations and side effects such as life-threatening ventricular arrhythmias and hypotension. The small conductance Ca2+-activated K+ channels (SK channels) are dependent on intracellular Ca2+ concentrations, which tightly integrate with membrane potential. Given the predominant expression in the atria of many species, including humans, they are now emerging as a therapeutic target for treating AF. This review aimed to illustrate the characteristics and function of SK channels. Moreover, it discussed the regulation of SK channels and their potential as a therapeutic target of AF.

Regulation of KCNMA1 transcription by Nrf2 in coronary arterial smooth muscle cells.

The large conductance Ca2+-activated K+ (BK) channels, composed of the pore-forming α subunits (BK-α, encoded by KCNMA1 gene) and the regulatory ß1 subunits (BK-ß1, encoded by KCNMB1 gene), play a unique role in the regulation of coronary vascular tone and myocardial perfusion by linking intracellular Ca2+ homeostasis with excitation-contraction coupling in coronary arterial smooth muscle cells (SMCs). The nuclear factor erythroid 2-related factor 2 (Nrf2) belongs to a member of basic leucine zipper transcription factor family that regulates the expression of antioxidant and detoxification enzymes by binding to the antioxidant response elements (AREs) of these target genes. We have previously reported that vascular BK-ß1 protein expression was tightly regulated by Nrf2. However, the molecular mechanism underlying the regulation of BK channel expression by Nrf2, particularly at transcription level, is unknown. In this study, we hypothesized that KCNMA1 and KCNMB1 are the target genes of Nrf2 transcriptional regulation. We found that BK channel protein expression and current density were diminished in freshly isolated coronary arterial SMCs of Nrf2 knockout (KO) mice. However, BK-α mRNA expression was reduced, but not that of BK-ß1 mRNA expression, in the arteries of Nrf2 KO mice. Promoter-Nrf2 luciferase reporter assay confirmed that Nrf2 binds to the ARE of KCNMA1 promoter, but not that of KCNMB1. Adenoviral expression and pharmacological activation of Nrf2 increased BK-α and BK-ß1 protein levels and enhanced BK channel activity in coronary arterial SMCs. Hence, our results indicate that Nrf2 is a key determinant of BK channel expression and function in vascular SMCs. Nrf2 facilitates BK-α expression through a direct increase in gene transcription, whereas that on BK-ß1 is through a different mechanism.

Glucose fluctuations promote vascular BK channels dysfunction via PKCα/NF-κB/MuRF1 signaling.

Glucose fluctuations may contribute to large conductance calcium activated potassium (BK) channel dysfunction. However, the underlying mechanisms remain elusive. The aim of this study was to investigate the molecular mechanisms involved in BK channel dysfunction as a result of glucose fluctuations. A rat diabetic model was established through the injection of streptozotocin. Glucose fluctuations in diabetic rats were induced via consumption and starvation. Rat coronary arteries were isolated and coronary vascular tensions were measured after three weeks. Rat coronary artery smooth muscle cells were isolated and whole-cell BK channel currents were recorded using a patch clamp technique. Human coronary artery smooth muscle cells in vitro were used to explore the underlying mechanisms. After incubation with iberiotoxin (IBTX), the Δ tensions (% Max) of rat coronary arteries in the controlled diabetes mellitus (C-DM), the uncontrolled DM (U-DM) and the DM with glucose fluctuation (GF-DM) groups were found to be 84.46 ± 5.75, 61.89 ± 10.20 and 14.77 ± 5.90, respectively (P < .05), while the current densities of the BK channels in the three groups were 43.09 ± 4.35 pA/pF, 34.23 ± 6.07 pA/pF and 17.87 ± 4.33 pA/pF, respectively (P < .05). The Δ tensions (% Max) of rat coronary arteries after applying IBTX in the GF-DM rats injected with 0.9% sodium chloride (NaCl) (GF-DM + NaCl) and the GF-DM rats injected with N-acetyl-L-cysteine (NAC) (GF-DM + NAC) groups were found to be 8.86 ± 1.09 and 48.90 ± 10.85, respectively (P < .05). Excessive oxidative stress and the activation of protein kinase C (PKC) α and nuclear factor (NF)-κB induced by glucose fluctuations promoted the decrease of BK-ß1 expression, while the inhibition of reactive oxygen species (ROS), PKCα, NF-κB and muscle ring finger protein 1 (MuRF1) reversed this effect. Glucose fluctuations aggravate BK channel dysfunction via the ROS overproduction and the PKCα/NF-κB/MuRF1 signaling pathway.

Glucose Fluctuations Promote Aortic Fibrosis through the ROS/p38 MAPK/Runx2 Signaling Pathway.

AIM: Glucose fluctuations may be responsible for, or further the onset of arterial hypertension, but the exact mechanisms remain unclear. The purpose of this study was to investigate the mechanisms behind and related to aortic fibrosis and aortic stiffening induced by glucose fluctuations. METHODS: Sprague-Dawley rats were injected with streptozotocin (STZ) and randomly divided into three treatment groups: controlled STZ-induced diabetes (C-STZ); uncontrolled STZ-induced diabetes (U-STZ); and STZ-induced diabetes with glucose fluctuations (STZ-GF). After 3 weeks, rat blood pressure (BP) was tested, and aortic fibrosis was detected by using the Masson trichrome staining technique. Levels of p38 mitogen-activated protein kinase (p38 MAPK), runt-related transcription factor 2 (Runx2), collagen type 1 (collagen I), and NADPH oxidases were determined by Western blot.Rat vascular smooth muscle cells in vitro were used to explore underlying mechanisms. RESULTS: The systolic BP of diabetic rats in the C-STZ, U-STZ, and STZ-GF groups was 127.67 ± 6.53, 150.03 ± 5.24, and 171.63 ± 3.53 mm Hg, respectively (p< 0.05). The mean BP of diabetic rats in the three groups was 91.20 ± 10.07, 117.29 ± 4.28, and 140.58 ± 2.14 mm Hg, respectively (p< 0.05). The diastolic BP of diabetic rats in the three groups was 73.20 ± 12.63, 101.93 ± 5.79, and 125.37 ± 4.62 mm Hg, respectively (p< 0.05). The ratios of fibrosis areas in the aortas of the three groups were 11.85 ± 1.23, 29.00 ± 0.87, and 48.36 ± 0.55, respectively (p< 0.05). The expressions of p38 MAPK, Runx2, and collagen I were significantly increased in the STZ-GF group. In vitro, applications of inhibitors of reactive oxygen species (ROS) and p38 MAPK successfully reversed glucose fluctuations that would have possibly induced aortic fibrosis. CONCLUSIONS: Blood glucose fluctuations aggravate aortic fibrosis via affecting the ROS/p38 MAPK /Runx2 signaling pathway.

Serum biomarkers combined with ultrasonography for early diagnosis of non-alcoholic fatty liver disease confirmed by magnetic resonance spectroscopy.

Magnetic resonance spectroscopy (MRS) is notably accurate for even minimal degree of hepatic steatosis in non-alcoholic fatty liver disease (NAFLD). But routine use of MRS is limited by its cost and availability. In this study, we developed a diagnostic model combining ultrasonography with biomarkers to identify mild NAFLD, with MRS as the reference standard. A total of 422 eligible subjects were enrolled. The serum levels of fibroblast growth factor 21 (FGF21), cytokeratin 18 M65ED, proteinase 3, neutrophil elastase, alpha-1 antitrypsin, and neutrophil elastase/alpha-1 antitrypsin were measured using ELISA assays. We found that among the six biomarkers, only serum FGF21 was independently associated with intrahepatic triglyceride content (IHTC, standardized ß = 0.185, P < 0.001) and was an independent risk factor for mild NAFLD. Thus, we established a Mild NAFLD Model based on FGF21, alanine transaminase, triglycerides, and body mass index. The area under the receiver-operating characteristic curve of the Mild NAFLD Model was 0.853 (95% confidence interval: 0.816-0.886). Furthermore, a two-step approach combining ultrasonography with the Mild NAFLD Model displayed a better sensitivity for diagnosing mild NAFLD compared with each method alone, with a sensitivity of 97.32% and a negative predictive value of 85.48%. This two-step approach combining ultrasonography and the Mild NAFLD Model derived from serum FGF21 improves the diagnosis of mild NAFLD and can be applied to the early diagnosis of NAFLD in clinical practice.

Kinetic Studies on Radical Scavenging Activity of Kaempferol Decreased by Sn(II) Binding.

Sn(II) binds to kaempferol (HKaem, 3,4',5,7-tetrahydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one) at the 3,4-site forming [Sn(II)(Kaem)2] complex in ethanol. DPPH• scavenging efficiency of HKaem is dramatically decreased by SnCl2 coordination due to formation of acid inhibiting deprotonation of HKaem as ligands and thus reduces the radical scavenging activity of the complex via a sequential proton-loss electron transfer (SPLET) mechanism. Moderate decreases in the radical scavenging of HKaem are observed by Sn(CH3COO)2 coordination and by contact between Sn and HKaem, in agreement with the increase in the oxidation potential of the complex compared to HKaem, leading to a decrease in antioxidant efficiency for fruits and vegetables with Sn as package materials.

Regulation of Coronary Arterial Large Conductance Ca2+-Activated K+ Channel Protein Expression and Function by n-3 Polyunsaturated Fatty Acids in Diabetic Rats.

AIM: The objective of this study was to examine the effects of n-3 polyunsaturated fatty acids (n-3 PUFAs) on coronary arterial large conductance Ca2+-activated K+ (BK) channel function in coronary smooth muscle cells (SMCs) of streptozotocin-induced diabetic rats. METHODS: The effects of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on coronary BK channel open probabilities were determined using the patch clamp technique. The mRNA and protein expressions of BK channel subunits were measured using qRT-PCR and Western blots. The coronary artery tension and coronary SMC Ca2+ concentrations were measured using a myograph system and fluorescence Ca2+ indicator. RESULTS: Compared to nondiabetic control rats, the BK channel function was impaired with a reduced response to EPA and DHA in freshly isolated SMCs of diabetic rats. Oral administration of n-3 PUFAs had no effects on protein expressions of BK channel subunits in nondiabetic rats, but significantly enhanced those of BK-ß1 in diabetic rats without altering BK-α protein levels. Moreover, coronary ring tension induced by iberiotoxin (a specific BK channel blocker) was increased and cytosolic Ca2+ concentrations in coronary SMCs were decreased in diabetic rats, but no changes were found in nondiabetic rats. CONCLUSIONS: n-3 PUFAs protect the coronary BK channel function and coronary vasoreactivity in diabetic rats as a result of not only increasing BK-ß1 protein expressions, but also decreasing coronary artery tension and coronary smooth muscle cytosolic Ca2+ concentrations.

Qualitative and Quantitative Assessment of Abdominal and Pelvic CT Image Quality Using Iopromide With Different Concentrations of Iodine (300 and 370 mg I/mL).

OBJECTIVE: The purpose of this study was to analyze the quality of MDCT images obtained using iopromide with two different concentrations of iodine (300 and 370 mg I/mL) in daily clinical settings. SUBJECTS AND METHODS: Patients from 38 hospitals in China undergoing abdominal or pelvic CT with iopromide were prospectively recruited. MDCT was performed using iopromide with an iodine concentration of 300 or 370 mg I/mL. CT quality image was graded as excellent, good, adequate, and poor. Objective indicators were the contrast-to-noise ratio (CNR) and signal-to-noise ratio (SNR). Outcomes were compared according to organ studied, tumor type (benign vs malignant), saline usage, and type of MDCT (16-MDCT vs 64-MDCT). RESULTS: A total of 4506 patients (63.7% men) with a mean (± SD) age of 56.3 ± 14.1 years and mean body mass index (weight in kilograms divided by the square of height in meters) of 23.2 ± 3.3 were included. Iopromide with 300 mg I/mL was used for 3042 patients (67.5%), and 370 mg I/mL was used for 1464 patients (32.2%). A total of 1847 scans (41.0%) had excellent image quality, 2454 (54.5%) had good quality, 176 (3.9%) had adequate quality, and 29 (0.6%) had poor quality. No differences were noted between CT scans that did or did not use saline, 16-MDCT versus 64-MDCT scans, and 300 versus 370 mg I/mL iopromide. Variations in the CNR and SNR were noted between the two iodine concentrations with respect to other parameters examined. CONCLUSION: Iopromide with both concentrations of iodine provided acceptable image quality, though according to CNR and SNR, one or the other may provide better quality in different situations.

[3D Reconstruction of PCL Based on MRI and CT Image Fusion].

OBJECTIVE: To reconstruct three-dimensional (3D) image of posterior cruciate ligament (PCL) based on MRI and CT image fusion. METHODS: CT and MRI scans were performed on 12 knees of young men. The Dicom data were extracted and unified. The outline of PCL on MRI imaging was drew and plugged into the CT data. Finally, the visible 3D image of PCL with adjacent bones was reconstructed. The imaging anatomical measurements were examined and compared with those in published literature. RESULTS: Two cases were excluded from this study because of data deviations. The 3D visible reconstruction of PCL was proved to be feasible on the other ten cases. CONCLUSION: Three-dimensional visible reconstruction of PCL based on CT and MRI image fusion is feasible, which can provide support for individualized treatment of PCL injuries. Further simplification with increased accuracy may be needed.

Wld(S) ameliorates renal injury in a type 1 diabetic mouse model.

Diabetic nephropathy (DN) is the leading cause of end-stage kidney disease worldwide. The purpose of this study is to investigate whether the Wld(S) (slow Wallerian degeneration; also known as Wld) gene plays a renoprotective role during the progression of DN. Diabetes was induced in 8-wk-old male wild-type (WT) and C57BL/Wld(S) mice by streptozotocin (STZ) injection. Blood and urinary variables including blood glucose, glycated hemoglobin (GHb), insulin, urea nitrogen, and albumin/creatinine ratio were assessed 4, 7, and 14 wk after STZ injection. Periodic acid-Schiff staining, Masson staining, and silver staining were performed for renal pathological analyses. In addition, the renal ultrastructure was observed by electron microscope. The activities of p38 and ERK signaling in renal cortical tissues were evaluated by Western blotting. NAD(+)/NADH ratio and NADPH oxidase activity were also measured. Moreover, the expressions of TNF-α, IL-1, and IL-6 were examined. We provide experimental evidence demonstrating that the Wld(S) gene is expressed in kidney cells and protects against the early stage of diabetes-induced renal dysfunction and extracellular matrix accumulation through delaying the reduction of the NAD(+)/NADH ratio, inhibiting the activation of p38 and ERK signaling, and suppressing oxidative stress as evidenced by the decreased NADPH oxidase activity and lower expression of TNF-α, IL-1, and IL-6.

The role and mechanism of heme oxygenase-1 in arrhythmias.

The global incidence and prevalence of arrhythmias are continuously increasing. However, the precise mechanisms of underlying arrhythmogenesis and the optimal measures for effective treatment remain incompletely understood. The inducible form of heme oxygenase, known as heme oxygenase-1 (HO-1), is recognized as a potent antioxidant molecule capable of exerting anti-inflammatory and anti-apoptotic effects. Recent research indicates that HO-1 plays a role in preventing arrhythmias by mitigating cardiac remodeling, including electrical remodeling, ion remodeling, and structural remodeling. This review aimed to consolidate current knowledge regarding the involvement of HO-1 in arrhythmias and elucidate its underlying mechanisms of action.