Ubiquitinome Analysis Uncovers Alterations in Synaptic Proteins and Glucose Metabolism Enzymes in the Hippocampi of Adolescent Mice Following Cold Exposure.

Cold exposure exerts negative effects on hippocampal nerve development in adolescent mice, but the underlying mechanisms are not fully understood. Given that ubiquitination is essential for neurodevelopmental processes, we attempted to investigate the effects of cold exposure on the hippocampus from the perspective of ubiquitination. By conducting a ubiquitinome analysis, we found that cold exposure caused changes in the ubiquitination levels of a variety of synaptic-associated proteins. We validated changes in postsynaptic density-95 (PSD-95) ubiquitination levels by immunoprecipitation, revealing reductions in both the K48 and K63 polyubiquitination levels of PSD-95. Golgi staining further demonstrated that cold exposure decreased the dendritic-spine density in the CA1 and CA3 regions of the hippocampus. Additionally, bioinformatics analysis revealed that differentially ubiquitinated proteins were enriched in the glycolytic, hypoxia-inducible factor-1 (HIF-1), and 5'-monophosphate (AMP)-activated protein kinase (AMPK) pathways. Protein expression analysis confirmed that cold exposure activated the mammalian target of rapamycin (mTOR)/HIF-1α pathway. We also observed suppression of pyruvate kinase M2 (PKM2) protein levels and the pyruvate kinase (PK) activity induced by cold exposure. Regarding oxidative phosphorylation, a dramatic decrease in mitochondrial respiratory-complex I activity was observed, along with reduced gene expression of the key subunits NADH: ubiquinone oxidoreductase core subunit V1 (Ndufv1) and Ndufv2. In summary, cold exposure negatively affects hippocampal neurodevelopment and causes abnormalities in energy homeostasis within the hippocampus.

A comprehensive review on immune checkpoint inhibitors induced cardiotoxicity characteristics and associated factors.

Newly approved cancer drugs called ICIs have shown remarkable success in improving patient survival rates, but they also have the potential for inflammatory and immune-related side effects, including those affecting the cardiovascular system. Research has been conducted to understand the development of these toxicities and identify risk factors. This review focuses on the characteristics of ICI-induced cardiotoxicity and discusses the reported risk factors. It is important for cardio-oncologists to understand the basic concepts of these drugs to better understand how cardiotoxicities occur. It might be hard to find reports, where all patients treated with ICIs had developed cardiac toxicity, because there could be other existing and variable factors that influence the likelihood or risk of developing cardiotoxicity during treatment. Various clinical parameters have been explored as potential risk factors, and further investigation is needed through large-scale studies.

The relationship between leukocyte to albumin ratio and atrial fibrillation severity.

BACKGROUND: An increased leukocyte count is a sign of inflammation and has been demonstrated to be a predisposing factor and complication of atrial fibrillation. Similarly, albumin, the major protein in the serum, is also considered an acute phase reactant protein that has osmotic and anti-inflammatory properties, and a low albumin level is a known factor associated with severity in many pathologies, including atrial fibrillation. The neutrophil percentage-to-albumin ratio (NPAR) and other emerging leukocyte counts/albumin ratios have been reliable systemic inflammation-based predictors of mortality and complications in various diseases, but they have not yet been used with atrial fibrillation. This study's aim was to explore whether the leukocyte to albumin ratio could also serve as a useful index in estimating atrial fibrillation severity, including the severity of atrial fibrillation secondary to stroke, to provide a new and more objective tool than the conventional and medical history-based CHA2DS2-VASc score. MATERIALS AND METHODS: Data were retrospectively collected from the Wuhan University Zhongnan Hospital database from January 1st to December 31st, 2021. The patients were classified into 2 groups: Group 1-low severity and Group 2- moderate to high severity, and diverse statistical analyses were conducted to evaluate the relationship between the leukocyte-to-albumin ratio and AF severity. RESULTS: Only 2329 test subjects met the inclusion criteria. We had 727 test subjects (381 males and 346 females) categorized into the low severity cohort and 1601 test subjects (932 males and 670 females) in the moderate to high severity group. The difference in mean age between the two groups was significant (95% CI [-2.682 to -0.154] p = 0.028), and the difference in the LAR mean rank between the two groups was significant (p = 0.00). The Chi-square test of association yielded the following results: the relationship between the LAR level and category of severity was statistically significant (p = 0.00), and the Mantel‒Haenszel statistic association odds ratio was OR = 0.657. 95% CI OR [0.549-0.787] p = 0.000. The association between sex and atrial fibrillation severity also reached statistical significance. However, sex and LAR were found to be independent factors in atrial fibrillation (Chi-square p value = 0.564). CONCLUSION: It has been demonstrated throughout this investigation that the leukocyte to albumin ratio could provide key clues in clinical practice and contribute to thromboembolism risk assessment in the setting of atrial fibrillation.

The BNP to Albumin Ratio and Heart Rate in Stroke Complicating Atrial Fibrillation.

Heart rate is still a controversial and unclear factor of stroke risk in atrial fibrillation. Indices combining parameters are more accurate predictors than single parameters. This article assessed the association of the BNP-to-albumin ratio (BAR), with the risk of stroke, and evaluated the relationship between heart rate and stroke risk. Data were retrospectively collected from the Zhongnan Hospital electronic records. Binary logistic regression assessed the association between BAR and the prediction of acute stroke in atrial fibrillation. Spearman's correlation analysis evaluated the correlation between heart rate and BAR. The specificity and sensitivity of the BAR index were determined by ROC curve analysis. A total of 197 participants were involved, including 119 cases and 78 controls. The mean BAR was significantly higher for cases than for controls P = 0.00 while the difference in mean heart rate did not reach statistical significance P = 0.08. Using binary logistic analysis, BAR was a significant predictor of stroke in AF, OR = 1.67 95%CI [1.09-2.55] P = 0.018. The correlation between BAR and heart rate was significant, the correlation coefficient was r = 0.15 P = 0.03. ROC curve analysis showed that at a cut-off value of 2.01*10-9 g/L 93% of patients with a BAR of less than 2.01 did not have an acute stroke and only the 60% with a BAR greater than 2.01 experienced an acute stroke. It's been suggested that the BNP to albumin ratio and heart rate could be used to estimate the risk of stroke among hospitalized atrial fibrillation patients, thus contributing to the implementation of appropriate measures.

Image fusion of integrating fluoroscopy into 3D computed tomography in guidance of left atrial appendage closure.

AIMS: We evaluated the feasibility of left atrial appendage (LAA) closure guided by the image fusion of integrating fluoroscopy into 3D computed tomography (CT). METHODS AND RESULTS: A total of 117 consecutive patients who underwent LAA closure with or without the image fusion were matched (1:2). Each LAA closure step of the Image fusion group was guided by the preprocedure CT and image fusion, especially in the plan of LAA measurement and transseptal puncture. All patients were successfully implanted with a WATCHMAN closure device. Comparing the two groups, the mean number of recapture times and the number of devices per patient of the Image fusion group were significantly lower (0.4 ± 0.5 vs. 0.7 ± 0.8, P = 0.031 and 1.0 ± 0.2 vs. 1.1 ± 0.3, P = 0.027, respectively). The one-time successful deployment rate by the support of the image fusion was higher than in the control group (66.7% vs. 44.9%, P = 0.026). Each case of the Image fusion group was completely occluded with one transseptal puncture, while five of the Non-image fusion group required redo transseptal punctures. During the 45-day follow-up, both group cases presented occlusion efficiency and no major adverse cardiac events were observed. CONCLUSION: Image fusion technique integrating fluoroscopy into the 3D CT is safe and feasible which can be easily incorporated into the procedural work-flow of percutaneous LAA closure. The fusion image can play an important alternative role in the plan of LAA measurement and transseptal puncture site for improving the LAA closure procedure.

One-stop strategy for treatment of atrial fibrillation: feasibility and safety of combining catheter ablation and left atrial appendage closure in a single procedure.

BACKGROUND: Catheter ablation is effective in restoring sinus rhythm and left atrial appendage closure (LAAC) is increasingly used for stroke prevention in patients with atrial fibrillation (AF). We aimed to observe the feasibility and safety of performing AF ablation and LAAC in a single (one-stop) procedure. METHODS: Consecutive AF patients who underwent the combined procedure of AF ablation and LAAC with WATCHMAN device between March 2017 and September 2018 were prospectively enrolled. Baseline and intra-procedural parameters were evaluated. Three-month and subsequent 1-year follow-up were performed in all and earlier-enrolled subjects, respectively. RESULTS: A total of 178 AF patients (94 males, 68.9 ±â€Š8.1 years) underwent the one-stop procedure with CHA2DS2-VASc score 3.3 ±â€Š1.5 and HAS-BLED score 1.6 ±â€Š1.0, respectively. Pulmonary vein isolation was achieved in all patients while additional linear ablation was applied if the operator deemed necessary, yielding immediate ablation success rate of 98.9% (176/178). In the subsequent LAAC, satisfactory seal (residual leak <5 mm) was achieved in all patients. One stroke and four cardiac perforations occurred peri-operatively. At 3-month follow-up, sinus rhythm and satisfactory seal were maintained in 153/178 (86.0%) and 178/178 (100%) patients, respectively. One stroke and one delayed cardiac tamponade occurred, while no device-related thrombus or device migration was observed. During the 1-year follow-up for the earlier enrolled subjects, 52/72 (72.2%) of the patients maintained sinus rhythm. There was no stroke or systemic embolism observed. CONCLUSION: Combining catheter ablation and LAAC in a single procedure can be successfully and safely performed in non-valvular AF patients of Chinese population.

The significance of transaminase ratio (AST/ALT) in acute myocardial infarction.

INTRODUCTION: Fernando De Ritis described the significance of the transaminase (AST/ALT) ratio in 1957, and since then it has been commonly used to screen liver diseases. The liver is sensitive to hemodynamic changes because it receives approximately one-quarter of total cardiac output. We aimed to investigate the AST/ALT ratio changes in patients with acute myocardial infarction without any history of liver diseases in the Chinese Han population. MATERIAL AND METHODS: We analyzed a total of 120 patients with acute myocardial infarction admitted to the cardiology department of Zhongnan Hospital of Wuhan University between January 2019 and June 2019. AST/ALT ratio of the first blood test was calculated for all patients. RESULTS: The mean De Ritis ratio (AST/ALT) was higher in patients with ST-segment elevation myocardial infarction (STEMI) (3.2261 ±2.41379) than in non-ST-segment elevation myocardial infarction (NSTEMI) (2.2089 ±1.63177) patients. The difference was statistically significant (p = 0.002). CONCLUSIONS: AST/ALT ≥ 2.0 has a strong association with total coronary occlusion. We might rely on this test to predict coronary occlusion without age difference.

Combined effect of M/A constituent and grain boundary on the impact toughness of CGHAZ and ICCGHAZ of E550 grade offshore engineering steel.

The present paper investigated the relationship between low temperature impact toughness and microstructure of bainite in coarse-grained heat affected zone (CGHAZ) and intercritically rehazed CGHAZ (ICCGHAZ) of an offshore engineering steel from both the microstructure morphological and crystallographic aspects. In this work, six groups of samples simulated CGHAZ and ICCGHAZ were designated at three different cooling rates. The Charpy test results showed that the toughness in CGHAZ decreases dramatically with decrease of cooling rate, which was attributed to the microstructural evolution from lath bainite to granular bainite, accompanying with the size increase of Bain zone and the change of M/A morphology from film to block. The increase in hardenability by cooling rate promotes more crystallographic variants from different Bain groups. Meanwhile, the combination with controlled inter-spacing of block boundaries by self-accommodation below the critical Griffith crack length, micro-crack can be arrested by these high angle grain boundaries thereby suppressed brittle fracture initiation and increased fracture properties. However, the variation in toughness of ICCGHAZ is not a concern, since obtaining excellent toughness is scarcely accessible even if the matrix microstructure is analogous to CGHAZ. It was due to the formation of coarse M/A constituents (~2 µm) necklacing at the prior austenite grain boundary. The visualized crystallography suggested that the impact toughness was partially correlated to the configuration manner and the size of Bain zones as well via promoting highly misoriented angle (>45°) boundaries, which in turn effectively deflected or arrested the brittle crack propagation.

Catheter ablation of ventricular arrhythmias originating from the para-Hisian region with reversed C-curve technique.

AIMS: Ventricular arrhythmias (VAs) originating from the para-Hisian region represent a challenging location. The long-term success rate of catheter ablation above the septal leaflet of the tricuspid valve is not ideal. This study aimed to investigate the safety and efficacy of catheter ablation for para-Hisian VAs via a direct approach under the septal valve with reversed C-curve technique. METHODS AND RESULTS: Twenty-five consecutive patients with para-Hisian VAs were included. Systematic mapping was performed in the right ventricle septum, including both the regions above and under the septal valve. Radiofrequency (RF) ablation was preferentially performed under the valve with reversed C-curve technique in all patients. If the ablation failed under the valve, it was then performed above the valve and even in aortic sinus cusps. The earliest ventricular activation preceding surface QRS (V-QRS) under the valve was significantly larger than that above the valve (34.8 ± 5.3 vs 27.8 ± 5.7 ms, P < .01). RF ablation under the valve with reversed C-curve technique achieved acute success in 22 of 25 (88%) patients. Junctional rhythm developed during ablation in 3 of 25 (12%) patients and no atrioventricular block occurred. In the remaining three patients, RF application above the valve failed to eliminate the VAs and one of them achieved successful ablation in the right coronary cusp. During a mean follow-up of 17.8 ± 9.4 months, no patients presented with VAs recurrence and no postprocedure complications occurred. CONCLUSIONS: Catheter ablation under the valve with reversed C-curve technique shows to be effective and safe for para-Hisian VAs.

[Study on the effect of hydraulic delivery vertebroplasty on vertebral morphology and bone cement diffusion].

OBJECTIVE: To evaluate the effect of different bone cement injection methods during percutaneous vertebroplasty(PVP) on vertebral morphology and cement diffusion. METHODS: The clinical data of 52 patients with single-segment osteoporotic vertebral compression fracture treated from January 2016 to December 2017 were retrospectively analyzed. The patients were divided into hydraumatic group (28 cases) and pusher group (24 cases) according to bone cement injection method during PVP. By comparing visual analogue scale(VAS), height of anterior vertebral body, compression ratio, kyphosis angle before and after operation and analyzing filling ratio of bone cement in the first 1/3, median line and back 1/3 of the vertebral body in lateral X-rays and the conditions of bone cement diffusion in AP X-rays were to evaluate the effect of different bone cement injection methods on vertebral morphology and cement diffusion. RESULTS: Postoperative VAS was obviously improved in all patients and hydraumatic group was better than pusher group(P<0.05). Postoperative height of anterior vertebral body, compression ratio and kyphosis angle obviously restored in all patients while there was no significant difference between two groups(P>0.05). There was no significant difference in filling ratio of bone cement in the first 1/3 and median line of the vertebral body by lateral X-ray films between two groups(P>0.05), but in the back 1/3 of the vertebral body filling ratio of bone cement in hydraumatic group was better than in pusher group(P<0.05). The distribution of bone cement from AP X-ray films were more significant in hydraumatic group(P<0.05). CONCLUSIONS: Hydraulic delivery vertebroplasty (HDVP) has better clinical efficacy and it can guarantee sufficient distribution of bone cement into the fractured vertebra and preferably restore the morphology of vertebral body, which is worthy of clinical application.

Comparative study of carvedilol and quinidine for inhibiting hKv4.3 channel stably expressed in HEK 293 cells.

The inhibition of transient outward potassium current (Ito) is the major ionic mechanism for quinidine to treat Brugada syndrome; however, quinidine is inaccessible in many countries. The present study compared the inhibitory effect of the nonselective ß-adrenergic blocker carvedilol with quinidine on human Kv4.3 (hKv4.3, encoding for Ito) channel and action potential notch using a whole-cell patch technique in HEK 293 cell line expressing KCND3 as well as in ventricular epicardial myocytes of rabbit hearts. It was found that carvedilol and quinidine inhibited hKv4.3 current in a concentration-dependent manner. The IC50 of carvedilol was 1.2 µM for inhibiting hKv4.3 charge area, while the IC50 of quinidine was 2.9 µM (0.2 Hz). Both carvedilol and quinidine showed typical open channel blocking properties (i.e. decreasing the time to peak of activation and increasing the inactivation of hKv4.3), negatively shifted the V1/2 of activation and inactivation, and slowed the recovery from inactivation of the channel. Although carvedilol had weaker in use- and rate-dependent inhibition of hKv4.3 peak current than quinidine, its reduction of the charge area was more than quinidine at all frequencies (0.2-3.3 Hz). Moreover, the inhibitory effect of carvedilol on action potential notch was greater than quinidine. These results provide the novel information that carvedilol, like quinidine, significantly inhibits hKv4.3 and action potential notch, suggesting that carvedilol is likely an alternative drug for preventing malignant ventricular arrhythmias in patients with Brugada syndrome in countries where quinidine is unavailable.

Clinical Features of Post Cardiac Injury Syndrome Following Catheter Ablation of Arrhythmias: Systematic Review and Additional Cases.

BACKGROUND: Post cardiac injury syndrome (PCIS) is a troublesome but not uncommon complication following catheter ablation of arrhythmias. We aimed to study the clinical features of ablation-associated PCIS. METHODS: For this purpose, we conducted a computerised literature search that identified 19 published cases, and we additionally included another two new cases from our centres. Twenty-one (21) cases of PCIS following ablation were analysed. RESULTS: Among the 21 cases, PCIS most commonly occurred after atrial flutter/fibrillation (AFL/AF) ablation (71.4%), followed by atrioventricular re-entrant tachycardia (AVRT) ablation (9.5%), atrioventricular node (AVN) ablation (9.5%), atrioventricular nodal re-entrant tachycardia (AVNRT) ablation (4.8%) and ventricular tachycardia (VT) ablation (4.8%). Thirty-eight (38) per cent of PCIS was suggested to be secondary to cardiac perforation. Specific symptoms or features include pleuritic chest pain (76.2%), fever (76.2%), elevated markers of inflammation (76.2%), pericardial effusion (90.5%), pleural effusion (71.4%) and pulmonary infiltrates (28.6%). Interestingly, all the six cases with pulmonary infiltrates were following AFL/AF ablation (6/15, 40%). Serious clinical manifestations include cardiac tamponade, massive pleural effusion with hypoalbuminaemia and hyponatraemia, and massive pulmonary infiltrates with hypoxaemia. Notably, empiric antibiotic therapy was used in seven cases including five with pulmonary infiltrates but failed to work. No mortality occurred during a mean follow-up of 4.1±5.3 (1 to 19) months. CONCLUSIONS: Catheter ablation of AFL/AF was most commonly involved in ablation-associated PCIS. Pulmonary infiltrate is an important feature of PCIS following AFL/AF ablation and may be misdiagnosed as pneumonia. Although PCIS is troublesome and even dangerous, it does carry a benign prognosis.

Perioperative Use of Levosimendan Improves Clinical Outcomes in Patients After Cardiac Surgery: A Systematic Review and Meta-Analysis.

Severe postoperative complications can affect cardiac surgery patients. Levosimendan is a novel calcium sensitizer commonly administered after cardiac surgery. However, the patient benefits are controversial. PubMed, Embase, and the Cochrane library were systematically searched for randomized controlled trials comparing levosimendan with control in adult cardiac surgery patients. Twenty-five studies (3247 patients) were included. Pooled data indicated that levosimendan reduced mortality after cardiac surgery [odds ratio (OR) 0.63, 95% confidence interval (CI): 0.47-0.84, P = 0.001]. However, this reduction was restricted to patients with low (<50%) left ventricular ejection fraction (OR 0.49, 95% CI: 0.35-0.70, P = 0.0001). It significantly reduced the incidence of postoperative acute kidney injury (OR 0.55, 95% CI: 0.41-0.74, P < 0.0001) and renal replacement therapy use (OR 0.56, 95% CI: 0.39-0.80, P = 0.002). Moreover, levosimendan significantly shortened the duration of the intensive care unit stay (weighted mean differences -0.49 day, 95% CI: -0.75 to -0.24, P = 0.0002) and mechanical ventilation use (weighted mean differences -2.30 hours, 95% CI: -3.76 to -0.84, P = 0.002). In conclusion, levosimendan reduced the mortality in patients with low left ventricular ejection fraction and decreased the incidence of acute renal injury and renal replacement therapy use. In addition, it shortened the duration of the intensive care unit stay and mechanical ventilation use.

Meta-Analysis of Risk of Ventricular Arrhythmias and All-Cause Mortality in Patients With Chronic Total Occlusion of a Coronary Artery and/or Implantable Cardioverter-Defibrillator.

Implantable cardioverter-defibrillator (ICD) has been increasingly used to prevent sudden death in patients with high risk of ventricular arrhythmias (VAs). Chronic total occlusion (CTO) is a severe condition of coronary artery disease. However, the prognostic impact of CTO in ICD recipients remains controversial. We systematically searched the PubMed, EMBASE, and Cochrane databases for documents published before October 1, 2017 to identify studies that investigated the prognostic impact of CTO on VAs and all-cause mortality (ACM) in ICD recipients. The effect size was expressed by hazard ratio (HR) and 95% confidence interval (CI). Overall, 6 studies with 1,423 patients were included. We found that CTO independently predicted the occurrence of VAs in the global population (HR 1.77, 95% CI 1.14 to 2.76, p = 0.01). Subgroup analysis revealed that CTO only predicted VAs in patients receiving ICD as secondary prevention (HR 1.96, 95% CI 1.55 to 2.48, p <0.01). However, CTO was not associated with ACM in the global population (HR 1.51, 95% CI 0.99 to 2.32, p = 0.06). Further subgroup analysis still showed no association between CTO and ACM in patients receiving ICD as primary prevention (HR 1.49, 95% CI 0.43 to 5.21, p = 0.53) or secondary prevention (HR 1.56, 95% CI 0.87 to 2.78, p = 0.13). In conclusion, CTO is an independent predictor of VAs in patients with secondary-prevention ICD, but not for ACM. Our study provided additional evidence for improving the risk stratification and management of VAs in ICD recipients.

De novo characterization of the Iris lactea var. chinensis transcriptome and an analysis of genes under cadmium or lead exposure.

Iris lactea var. chinensis (I. lactea var. chinensis) is tolerant to accumulations of cadmium (Cd) and lead (Pb). In this study, the transcriptome of I. lactea var. chinensis was investigated under Cd or Pb stresses. Using the gene ontology database, 31,974 unigenes were classified into biological process, cellular component and molecular function. In total, 13,132 unigenes were involved in enriched Encyclopedia of Genes and Genomes (KEGG) metabolic pathways, and the expression levels of 5904 unigenes were significantly changed after exposure to Cd or Pb stresses. Of these, 974 were co-up-regulated and 1281 were co-down-regulated under the two stresses. The transcriptome expression profiles of I. lactea var. chinensis under Cd or Pb stresses obtained in this study provided a resource for identifying common mechanisms in the detoxification of different heavy metals. Furthermore, the identified unigenes may be used for the genetic breeding of heavy-metal tolerant plants.

Larger rate dependence of late sodium current in cardiac Purkinje cells: A potential link to arrhythmogenesis.

BACKGROUND: Purkinje cells (PCs) have a steeper rate dependence of repolarization and are more susceptible to arrhythmic activity than do ventricular myocytes (VMs). Late sodium current (INaL) is rate dependent and contributes to rate dependence of repolarization. OBJECTIVE: This study sought to test our hypothesis that PCs have a larger rate dependence of INaL, contributing to their steeper rate dependence of repolarization and higher susceptibility to arrhythmic activity, than do VMs. METHODS: INaL was recorded in isolated rabbit PCs and VMs with the whole-cell patch clamp technique. Action potential was examined using the microelectrode technique. RESULTS: Compared with VMs, PCs exhibited a significantly larger rate dependence of INaL with a larger INaL to basic cycle length (BCL) slope. Moreover, PCs had a larger rate dependence of INaL decay and slower recovery kinetics. Interestingly, the larger rate dependence of INaL matched to a steeper rate dependence of action potential duration (APD) in PCs. The INaL blocker tetrodotoxin significantly blunted, while the INaL enhancer anemone toxin (ATX-II) significantly increased, the rate dependence of INaL and APD in PCs and VMs. In the presence of ATX-II, the rate dependence of INaL in PCs was markedly larger than that in VMs, causing a much steeper rate dependence of APD in PCs. Accordingly, PCs exhibited greater rate-dependent electrical instability and were more prone to ATX-II-induced early afterdepolarizations, which were completely inhibited by the INaL inhibitor ranolazine. CONCLUSION: PCs have a significantly larger rate dependence of INaL than do VMs because of distinctive INaL decay and recovery kinetics, which contributes to their larger rate adaptation, and simultaneously predisposes them to a higher risk of arrhythmogenesis.

Effects of ginseng-spikenard heart-nourishing capsule on inactivation of C-type Kv1.4 potassium channel.

This research is to explore the effects of traditional Chinese medicine Ginseng-spikenard heart-nourishing capsule on the inactivation of c-type Kv1.4 channels (Kv1.4∆N) in Xenopus laevis oocytes with two-electrode voltageclamp technique. Defolliculated oocytes (stage V-VI) were injected with transcribed cRNAs of ferret Kv1.4δN channels. During recording, oocytes were continuously perfused with ND96 solution (control group) and solution prepared from Ginseng-spikenard heart-nourishing capsule (experimental group). Results found that, at the command potential of +50 mV, the current of experimental group was reduced to 48.33±4.0% of that in control group. The inactivation time constants in control and experimental groups were 2962.56±175.35 ms and 304.13±36.22ms, respectively (P<0.05, n=7). The recovery time of fKv1.4∆N channel after inactivation in control group and experimental groups was 987±68.39 ms and 1734.15±98.45 ms, respectively (P<0.05, n=5). Ginseng-spikenard heart-nourishing capsule can inhibit the Kv1.4δN channel, which may be one of the mechanisms of underlying antiarrhythmia.

Docosahexaenoic Acid Attenuates Doxorubicin-induced Cytotoxicity and Inflammation by Suppressing NF-κB/iNOS/NO Signaling Pathway Activation in H9C2 Cardiac Cells.

Doxorubicin (DOX) is a widely used antineoplastic agent for a variety of carcinomas. However, it is cardiotoxic and leads to cardiomyopathy. Previous studies have indicated that omega-3 polyunsaturated acids (ω-3 PUFAs) have therapeutic effects on dilated and diabetic cardiomyopathies. However, whether ω-3 PUFAs exert therapeutic effects on DOX-induced cardiomyopathy remains unclear. In this study, we explored the effect and underlying mechanisms of docosahexaenoic acid (DHA), an important type of ω-3 PUFA, on DOX-induced cardiotoxicity and inflammation. H9C2 cardiac cells were exposed to DOX (5 µM) and interfered with by DHA (10 µM) for 4 hours. The effect of DHA on H9C2 cell viability was measured by Cell Counting Kit-8 assay. The levels of mRNA and protein expression of inflammatory cytokines were determined by real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. Reactive oxygen species and nitric oxide (NO) levels were determined by corresponding kits. The protein expression of key molecules in the nuclear factor-kappa B/inducible isoform of nitric oxide synthase/nitric oxide (NF-κB/iNOS/NO) signaling pathway was determined by western blotting. DOX-induced significant cytotoxicity and reactive oxygen species production in H9C2 cardiac cells. It also induced cardiac inflammation as evidenced by significantly increased expressions of inflammatory cytokines, including tumor necrosis factor-α, interleukin-6, interleukin-1ß, monocyte chemoattractant protein-1, and inducible isoform of NO synthase. However, DHA effectively attenuated DOX-induced cytotoxicity and inflammation. A further mechanistic study revealed that DHA suppressed DOX-induced activation of the NF-κB/iNOS/NO signaling pathway in H9C2 cells. Our results indicate that DHA may protect against DOX-induced cardiotoxicity by inhibiting NF-κB/iNOS/NO signaling pathway activation.

[Response in cuttings of Taxodium hybrid 'Zhongshanshan' and their parents to drought and re-hydration.] / ä¸­å±±æ‰åŠå ¶çˆ¶æ¯æœ¬å¹¼è‹—å¯¹å¹²æ—±èƒè¿«å’Œå¤æ°´çš„å“åº”.

In this study, three different strains of Taxodium hybrid 'Zhongshanshan' varieties [T. hybrid 302 (T. distichum♀×T. mucronatum♂), T. hybrid 407 (T. mucronatum♀×T. distichum♂), T. hybrid 118 (T. hybrid 302 ♀×T. macronatum ♂)] and their parents, T. distichum and T. mucronatum, were applied to investigate the response of photosynthetic characteristics, antioxidant enzyme systems and morphological characteristics to drought stress and recovery. The results indicated that as drought days were prolonged, all plants' net photosynthetic rate (Pn) decreased, while proline accumulated. Meanwhile, the antioxidases functioned to eliminate malonaldehyde toxicity. On the 8th day, the decrease of Pn of T. distichum was the biggest, T. hybrid 118 plants showed the highest water use efficiency and the smallest MDA content, while T. macronatum plants increased the activity of superoxide dismutase and content of proline. After rewatering for 2 days, all these parameters showed signs of recovery, and the T. hybrid 118 plants showed the fastest recovery rate since their Pn and proline content had recovered for 74.4% and 60.2%, respectively. Then after recovered for 9 days, all tested parameters had almost restored to equivalent levels of CK plants. The total biomass of T. hybrid 118 plants was not affected, while the ratio of root to shoot was significantly (P<0.05) increased. The drought-resistance capacity ranged as T. macronatum>T. hybrid 118>T. hybrid 407>T. hybrid 302>T. distichum plants. In conclusion, the backcross generation T. hybrid 118 plants largely inherited the drought resistance of T. mucronatum, and the result would be instrumental in breeding and popularization of drought-resistant hybrid varieties.