Association between Remnant Cholesterol and Metabolic Syndrome among Chinese Adults: Chinese Nutrition and Health Surveillance (2015-2017).

BACKGROUND: Remnant cholesterol (RC) is highly associated with several chronic diseases. However, the relationship between RC and Metabolic syndrome (MetS) remains unclear. The study's objective is to illustrate the relationship of RC to MetS. METHODS: The data were collected from the Chinese Nutrition and Health Surveillance (2015-2017), which included personal, household and dietary information. A total of 65,618 residents aged 20 years or older from 31 provinces in mainland China were included in this study. RC was calculated by the equation RC = TC - (LDL-C + HDL-C). The criteria for MetS were based on the 2020 Chinese Type 2 Diabetes Prevention and Treatment Guidelines. Logistic regression models were used to analyse the relationship between RC and MetS and every MetS component. The receiver operating characteristic (ROC) curve was established to evaluate the accuracy of RC in identifying MetS, and the area under the curve (AUC) and the best threshold were calculated. RESULTS: The weighted RC level of Chinese residents aged 20 years or older was 0.48 mmol/L. Participants with high RC levels were likely to be elderly, have a higher prevalence of MetS, higher total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), fasting blood glucose (FBG), hba1c, and lower high-density lipoprotein cholesterol (HDL-C). Sex, body mass index (BMI), education status, household yearly income per capita, marital status, area of the country, residence location, smoking status, fruit intake and sleep time had statistical differences in the RC group (p < 0.05). The OR of MetS gradually increased with an increase in the RC quartile (p < 0.01), and higher quartiles of RC (Q4) suggested the highest MetS risk. The prevalence of each MetS component gradually increased with an increase in the RC quartile. The ROC curve found that to identify MetS, the AUC and best threshold of RC were 0.71 and 0.52 mmol/L, respectively. CONCLUSIONS: RC had a positive association with MetS and each MetS component. The accuracy in identifying MetS was higher in RC than in other indexes. The current study could provide new scientific evidence for the early prevention and control of MetS.

Inhibitory effect of human interleukin-24 on the proliferation, migration, and invasion of cervical cancer cells.

OBJECTIVE: This study aimed to identify significantly differentially expressed genes (DEGs) related to cervical cancer by exploring extensive gene expression datasets to unveil new therapeutic targets. METHODS: Gene expression profiles were extracted from the Gene Expression Omnibus, The Cancer Genome Atlas, and the Genotype-Tissue Expression platforms. A differential expression analysis identified DEGs in cervical cancer cases. Weighted gene co-expression network analysis (WGCNA) was implemented to locate genes closely linked to the clinical traits of diseases. Machine learning algorithms, including LASSO regression and the random forest algorithm, were applied to pinpoint key genes. RESULTS: The investigation successfully isolated DEGs pertinent to cervical cancer. Interleukin-24 was recognized as a pivotal gene via WGCNA and machine learning techniques. Experimental validations demonstrated that human interleukin (hIL)-24 inhibited proliferation, migration, and invasion, while promoting apoptosis, in SiHa and HeLa cervical cancer cells, affirming its role as a therapeutic target. CONCLUSION: The multi-database analysis strategy employed herein emphasized hIL-24 as a principal gene in cervical cancer pathogenesis. The findings suggest hIL-24 as a promising candidate for targeted therapy, offering a potential avenue for innovative treatment modalities. This study enhances the understanding of molecular mechanisms of cervical cancer and aids in the pursuit of novel oncological therapies.

Targeting myocardial inflammation: investigating the therapeutic potential of atrial natriuretic peptide in atrial fibrosis.

BACKGROUND: Atrial Fibrillation (AF), a prevalent arrhythmic condition, is intricately associated with atrial fibrosis, a major pathological contributor. Central to the development of atrial fibrosis is myocardial inflammation. This study focuses on Atrial Natriuretic Peptide (ANP) and its role in mitigating atrial fibrosis, aiming to elucidate the specific mechanisms by which ANP exerts its effects, with an emphasis on fibroblast dynamics. METHODS AND RESULTS: The study involved forty Sprague-Dawley rats, divided into four groups: control, Angiotensin II (Ang II), Ang II + ANP, and ANP only. The administration of 1 µg/kg/min Ang II was given to Ang II and Ang II + ANP groups, while both Ang II + ANP and ANP groups received 0.1 µg/kg/min ANP intravenously for a duration of 14 days. Cardiac fibroblasts were used for in vitro validation of the proposed mechanisms. The study observed that rats in the Ang II and Ang II + ANP groups showed an increase in blood pressure and a decrease in body weight, more pronounced in the Ang II group. Diastolic dysfunction, a characteristic of the Ang II group, was alleviated by ANP. Additionally, ANP significantly reduced Ang II-induced atrial fibrosis, myofibroblast proliferation, collagen overexpression, macrophage infiltration, and the elevated expression of Interleukin 6 (IL-6) and Tenascin-C (TN-C). Transcriptomic sequencing indicated enhanced PI3K/Akt signaling in the Ang II group. Furthermore, in vitro studies showed that ANP, along with the PI3K inhibitor LY294002, effectively reduced PI3K/Akt pathway activation and the expression of TN-C, collagen-I, and collagen-III, which were induced by Ang II. CONCLUSIONS: The study demonstrates ANP's potential in inhibiting myocardial inflammation and reducing atrial fibrosis. Notably, ANP's effect in countering atrial fibrosis seems to be mediated through the suppression of the Ang II-induced PI3K/Akt-Tenascin-C signaling pathway. These insights enhance our understanding of AF pathogenesis and position ANP as a potential therapeutic agent for treating atrial fibrosis.

Non-contrast computed tomography-based radiomics for staging of connective tissue disease-associated interstitial lung disease.

Rationale and introduction: It is of significance to assess the severity and predict the mortality of patients with connective tissue disease-associated interstitial lung disease (CTD-ILD). In this double-center retrospective study, we developed and validated a radiomics nomogram for clinical management by using the ILD-GAP (gender, age, and pulmonary physiology) index system. Materials and methods: Patients with CTD-ILD were staged using the ILD-GAP index system. A clinical factor model was built by demographics and CT features, and a radiomics signature was developed using radiomics features extracted from CT images. Combined with the radiomics signature and independent clinical factors, a radiomics nomogram was constructed and evaluated by the area under the curve (AUC) from receiver operating characteristic (ROC) analyses. The models were externally validated in dataset 2 to evaluate the model generalization ability using ROC analysis. Results: A total of 245 patients from two clinical centers (dataset 1, n = 202; dataset 2, n = 43) were screened. Pack-years of smoking, traction bronchiectasis, and nine radiomics features were used to build the radiomics nomogram, which showed favorable calibration and discrimination in the training cohort {AUC, 0.887 [95% confidence interval (CI): 0.827-0.940]}, the internal validation cohort [AUC, 0.885 (95% CI: 0.816-0.922)], and the external validation cohort [AUC, 0.85 (95% CI: 0.720-0.919)]. Decision curve analysis demonstrated that the nomogram outperformed the clinical factor model and radiomics signature in terms of clinical usefulness. Conclusion: The CT-based radiomics nomogram showed favorable efficacy in predicting individual ILD-GAP stages.

CT-based radiomics nomogram for differentiation of adrenal hyperplasia from lipid-poor adenoma: an exploratory study.

BACKGROUND: To establish and verify a radiomics nomogram for differentiating isolated micronodular adrenal hyperplasia (iMAD) from lipid-poor adenoma (LPA) based on computed tomography (CT)-extracted radiomic features. METHODS: A total of 148 patients with iMAD or LPA were divided into three cohorts: a training cohort (n = 72; 37 iMAD and 35 LPA), a validation cohort (n = 36; 22 iMAD and 14 LPA), and an external validation cohort (n = 40; 20 iMAD and 20 LPA). Radiomics features were extracted from contrast-enhanced and non-contrast CT images. The least absolute shrinkage and selection operator (LASSO) method was applied to develop a triphasic radiomics model and unenhanced radiomics model using reproducible radiomics features. A clinical model was constructed using certain laboratory variables and CT findings. Radiomics nomogram was established by selected radiomics signature and clinical factors. Nomogram performance was assessed by calibration curve, the areas under receiver operating characteristic curves (AUC), and decision curve analysis (DCA). RESULTS: Eleven and eight extracted features were finally selected to construct an unenhanced radiomics model and a triphasic radiomics model, respectively. There was no significant difference in AUC between the two models in the external validation cohort (0.838 vs. 0.843, p = 0.949). The radiomics nomogram inclusive of the unenhanced model, maximum diameter, and aldosterone showed the AUC of 0.951, 0.938, and 0.893 for the training, validation, and external validation cohorts, respectively. The nomogram showed good calibration, and the DCA demonstrated the superiority of the nomogram compared with the clinical factors model alone in terms of clinical usefulness. CONCLUSIONS: A radiomics nomogram based on unenhanced CT images and clinical variables showed favorable performance for distinguishing iMAD from LPA. In addition, an efficient unenhanced model can help avoid extra contrast-enhanced scanning and radiation risk.

Identification of pyroptosis-related subtypes, development of a prognostic model, and characterization of tumour microenvironment infiltration in gastric cancer.

As a new programmed death mode, pyroptosis plays an indispensable role in gastric cancer (GC) and has strong immunotherapy potential, but the specific pathogenic mechanism and antitumor function remain unclear. We comprehensively analysed the overall changes of pyroptosis-related genes (PRGs) at the genomic and epigenetic levels in 886 GC patients. We identified two molecular subtypes by consensus unsupervised clustering analysis. Then, we calculated the risk score and constructed the risk model for predicting prognostic and selected nine PRGs related genes (IL18RAP, CTLA4, SLC2A3, IL1A, KRT7,PEG10, IGFBP2, GPA33, and DES) through LASSO and COX regression analyses in the training cohorts and were verified in the test cohorts. Consequently, a highly accurate nomogram for improving the clinical applicability of the risk score was constructed. Besides, we found that multi-layer PRGs alterations were correlated with patient clinicopathological features, prognosis, immune infiltration and TME characteristics. The low risk group mainly characterized by increased microsatellite hyperinstability, tumour mutational burden and immune infiltration. The group had lower stromal cell content, higher immune cell content and lower tumour purity. Moreover, risk score was positively correlated with T regulatory cells, M1 and M2 macrophages. In addition, the risk score was significantly associated with the cancer stem cell index and chemotherapeutic drug sensitivity. This study revealed the genomic, transcriptional and TME multiomics features of PRGs and deeply explored the potential role of pyroptosis in the TME, clinicopathological features and prognosis in GC. This study provides a new immune strategy and prediction model for clinical treatment and prognosis evaluation.

The Long-Term Impact of Bariatric Surgery on Development of Atrial Fibrillation and Cardiovascular Events in Obese Patients: An Historical Cohort Study.

Objective: To determine whether early Roux-en-Y gastric bypass surgery (RYGB) reduces the risk of Major adverse cardiovascular events (MACE) in patients with obesity. Patients and Methods: We conducted a study of patients with class II and III obesity [body mass index (BMI) > 35 kg/m2] from Olmsted County, Minnesota, who underwent obesity clinic consultation between the years 1993-2012, and had either RYGB surgery within 1 year (RYGB-1Y group), or medically managed (No-RYGB group). The composite endpoint of MACE (all-cause mortality, stroke, heart failure admission and acute myocardial infarction) was the primary endpoint, with new-onset AF as the secondary endpoint. Results: Of the 1,009 study patients, 308 had RYGB-1Y and 701 were medically managed (No-RYGB). Overall, the age was 44.0 ± 12.4 (mean ± SD) years; BMI was 45.0 ± 6.8 kg/m2. The RYGB-1Y group had a lower rate of MACE (adjusted hazard ratio (HR), 0.62; 95% CI, 0.44-0.88; P = 0.008) and lower mortality (adjusted HR, 0.51; 95% CI, 0.26-0.96; P = 0.04) than the No-RYGB group. The RYGB-1Y surgery was not associated with lower AF occurrence (HR, 0.66; 95% CI, 0.40-1.10; P = 0.11). Conclusion: An early RYGB approach for BMI reduction was associated with lower rates of MACE.

Neuroprotective mechanism of L-cysteine after subarachnoid hemorrhage.

Hydrogen sulfide, which can be generated in the central nervous system from the sulfhydryl-containing amino acid, L-cysteine, by cystathionine-ß-synthase, may exert protective effects in experimental subarachnoid hemorrhage; however, the mechanism underlying this effect is unknown. This study explored the mechanism using a subarachnoid hemorrhage rat model induced by an endovascular perforation technique. Rats were treated with an intraperitoneal injection of 100 mM L-cysteine (30 µL) 30 minutes after subarachnoid hemorrhage. At 48 hours after subarachnoid hemorrhage, hematoxylin-eosin staining was used to detect changes in prefrontal cortex cells. L-cysteine significantly reduced cell edema. Neurological function was assessed using a modified Garcia score. Brain water content was measured by the wet-dry method. L-cysteine significantly reduced neurological deficits and cerebral edema after subarachnoid hemorrhage. Immunofluorescence was used to detect the number of activated microglia. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the levels of interleukin 1ß and CD86 mRNA in the prefrontal cortex. L-cysteine inhibited microglial activation in the prefrontal cortex and reduced the mRNA levels of interleukin 1ß and CD86. RT-PCR and western blot analysis of the complement system showed that L-cysteine reduced expression of the complement factors, C1q, C3α and its receptor C3aR1, and the deposition of C1q in the prefrontal cortex. Dihydroethidium staining was applied to detect changes in reactive oxygen species, and immunohistochemistry was used to detect the number of NRF2- and HO-1-positive cells. L-cysteine reduced the level of reactive oxygen species in the prefrontal cortex and the number of NRF2- and HO-1-positive cells. Western blot assays and immunohistochemistry were used to detect the protein levels of CHOP and GRP78 in the prefrontal cortex and the number of CHOP- and GRP78-positive cells. L-cysteine reduced CHOP and GRP78 levels and the number of CHOP- and GRP78-positive cells. The cystathionine-ß-synthase inhibitor, aminooxyacetic acid, significantly reversed the above neuroprotective effects of L-cysteine. Taken together, L-cysteine can play a neuroprotective role by regulating neuroinflammation, complement deposition, oxidative stress and endoplasmic reticulum stress. The study was approved by the Animals Ethics Committee of Shandong University, China on February 22, 2016 (approval No. LL-201602022).

Evaluation of H2S-producing enzymes in cerebrospinal fluid and its relationship with interleukin-6 and neurologic deficits in subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Recent studies have suggested that H2S may be involved in the pathophysiology of subarachnoid hemorrhage (SAH). Endogenous H2S is mainly formed by cystathionine ß-synthase (CBS), d-amino-acid oxidase (DAO), and 3-mercaptopyruvate sulfotransferase (3-MST) from the substrate cysteine in the central nervous system. In this study, we assessed the expression of CBS, 3-MST, and DAO in cerebrospinal fluid (CSF) from patients with SAH and rats and the expression in the rat brain. METHODS: CSF samples were collected within 48 h of aneurysm rupture in SAH patients. The CBS, DAO and 3-MST levels in CSF were measured using Western blot analyses, and correlations with the inflammatory parameter Interleukin-6 (IL-6) were assessed. Six months after SAH, the clinical outcomes were assessed. RESULTS: In human CSF samples, the CBS and DAO protein levels were detected and increased after SAH. However, 3-MST was not detected in the control group CSF but increased after SAH. Strong correlations were observed between the increasing levels of CBS, DAO, and 3-MST and IL-6 2 days after SAH. Furthermore, high CBS, 3-MST and DAO levels in the CSF samples were correlated with poor outcomes at 6 months after SAH onset. We also found that the expression of CBS, DAO and 3-MST in the rat CSF and brain (parietal cortex and hippocampus) increased following SAH. We detected strong correlations between the increases in CBS, 3-MST and IL-6 in the rat CSF and brain samples. CONCLUSIONS: These results indicate that the upregulated expression of CBS, DAO and 3-MST after SAH was closely associated with the inflammatory response and neurological deficits after SAH.

Exosomes Derived From Bone Marrow Mesenchymal Stem Cells Inhibit Complement Activation In Rats With Spinal Cord Injury.

PURPOSE: Spinal cord injury (SCI) is a relatively common, devastating traumatic condition resulting in permanent disability. In this study, the use of exosomes derived from bone mesenchymal stem cells (BMSCs-Exo) as a cell-free therapy for the treatment of SCI in rats was investigated to gain insights into their mechanisms of action. METHODS: Rats were randomly divided into three groups, Sham (treated with PBS), SCI (SCI injury + PBS) and SCI + Exo (SCI injury + BMSCs-Exo). Changes in the complement system between the three groups were assessed with the use of proteomics. The proteomic data were verified using reverse transcription-polymerase chain reaction (RT-PCR). In addition, the distributions of BMSCs-Exo in rats with SCI were detected by immunofluorescence. Moreover, SCI-activated NF-κB levels were determined using Western blot. RESULTS: SCI insult increased complement levels, including C4, C5, C6, C4 binding protein alpha and complement factor H. In contrast, the SCI + BMSCs-Exo group exhibited attenuated SCI-induced complement levels. Immunofluorescence assay results revealed that BMSCs-Exo mainly accumulated at the spinal cord injury site and were bound to microglia cells. Western blot analysis of tissue lysates showed that BMSCs-Exo treatment also inhibited SCI-activated nuclear factor kappa-B (NF-κB). CONCLUSION: BMSCs-Exo play a protective role in spinal cord injury by inhibiting complement mRNA synthesis and release and by inhibiting SCI-activated NF-κB by binding to microglia.

Resveratrol reduces brain injury after subarachnoid hemorrhage by inhibiting oxidative stress and endoplasmic reticulum stress.

Previous studies have shown that resveratrol, a bioactive substance found in many plants, can reduce early brain injury after subarachnoid hemorrhage, but how it acts is still unclear. This study explored the mechanism using the experimental subarachnoid hemorrhage rat model established by injecting autologous blood into the cerebellomedullary cistern. Rat models were treated with an intraperitoneal injection of 60 mg/kg resveratrol 2, 6, 24 and 46 hours after injury. At 48 hours after injury, their neurological function was assessed using a modified Garcia score. Brain edema was measured by the wet-dry method. Neuronal apoptosis in the prefrontal cortex was detected by terminal deoxyribonucleotidyl transferase-mediated biotin-16-dUTP nick-end labeling assay. Levels of reactive oxygen species and malondialdehyde in the prefrontal cortex were determined by colorimetry. CHOP, glucose-regulated protein 78, nuclear factor-erythroid 2-related factor 2 and heme oxygenase-1 mRNA expression levels in the prefrontal cortex were measured by reverse transcription polymerase chain reaction. Tumor necrosis factor-alpha content in the prefrontal cortex was detected by enzyme linked immunosorbent assay. Immunohistochemical staining was used to detect the number of positive cells of nuclear factor-erythroid 2-related factor 2, heme oxygenase 1, glucose-regulated protein 78, CHOP and glial fibrillary acidic protein. Western blot assay was utilized to analyze the expression levels of nuclear factor-erythroid 2-related factor 2, heme oxygenase 1, glucose-regulated protein 78 and CHOP protein expression levels in the prefrontal cortex. The results showed that resveratrol treatment markedly alleviated neurological deficits and brain edema in experimental subarachnoid hemorrhage rats, and reduced neuronal apoptosis in the prefrontal cortex. Resveratrol reduced the levels of reactive oxygen species and malondialdehyde, and increased the expression of nuclear factor-erythroid 2-related factor 2, heme oxygenase-1 mRNA and protein in the prefrontal cortex. Resveratrol decreased glucose-regulated protein 78, CHOP mRNA and protein expression and tumor necrosis factor-alpha level. It also activated astrocytes. The results suggest that resveratrol exerted neuroprotective effect on subarachnoid hemorrhage by reducing oxidative damage, endoplasmic reticulum stress and neuroinflammation. The study was approved by the Animals Ethics Committee of Shandong University, China on February 22, 2016 (approval No. LL-201602022).

Mesenchymal stem cell derived EVs mediate neuroprotection after spinal cord injury in rats via the microRNA-21-5p/FasL gene axis.

Spinal cord injury (SCI) represents a relatively common type of motor system trauma. While the SCI patient will experience varying degrees of paraplegia and quadriplegia, which severely affects their quality of life, a heavy burden is also placed on the family and society as a whole. The exact pathogenic mechanisms underlying this condition remain unknown and no specific treatments are currently available. Findings from recent studies have shown that mesenchymal stem cells (MSCs), derived from extracellular vesicles (EVs) can reduce apoptosis, inflammation and promote angiogenesis after SCI. However, the mechanisms through which EVs exert these effects have yet to be identified, indicating the necessity for further investigation. In the present study, we report that treatment with MSCs-EVs significantly improved functional recovery and attenuated lesion size and apoptosis in a rat model of SCI. These MSCs-EVs were found to be directed to the spinal injury site and mainly incorporated into neurons within the lesioned site of the spinal cord. Tandem Mass Tags quantitative proteomics was applied to compare protein changes after SCI and MSCs-EVs treatment. A total of 883 differential proteins were identified, many of which being associated with apoptosis and inflammation. Subsequently, miRNA contents of MSCs-EVs were determined using qRT-PCR, with the result that miR-21-5p was one of the most highly expressed miRNA in these MSCs-EVs. Moreover, inhibition of miR-21-5p in MSCs-EVs significantly reversed the beneficial effects of MSCs-EVs on motor function and apoptosis, an effect which was associated with modulating FasL expression. The data suggest that modulation of the MSCs-EVs miR-21-5p/FasL gene axis may serve as a promising strategy for clinical treatment of SCI and other neurological diseases.

L-Cysteine-Derived H2S Promotes Microglia M2 Polarization via Activation of the AMPK Pathway in Hypoxia-Ischemic Neonatal Mice.

We have reported previously that L-cysteine-derived hydrogen sulfide (H2S) demonstrates a remarkable neuroprotective effect against hypoxia-ischemic (HI) insult in neonatal animals. Here, we assessed some of the mechanisms of this protection as exerted by L-cysteine. Specifically, we examined the capacity for L-cysteine to stimulate microglial polarization of the M2 phenotype and its modulation of complement expression in response to HI in neonatal mice. L-cysteine treatment suppressed the production of inflammatory cytokines, while dramatically up-regulating levels of anti-inflammatory cytokines in the damaged cortex. This L-cysteine administration promoted the conversion of microglia from an inflammatory M1 to an anti-inflammatory M2 phenotype, an effect which was associated with inhibiting the p38 and/or JNK pro-inflammatory pathways, nuclear factor-κB activation and a decrease in HI-derived levels of the C1q, C3a and C3a complement receptor proteins. Notably, blockade of H2S-production clearly prevented L-cysteine-mediated M2 polarization and complement expression. L-cysteine also inhibited neuronal apoptosis as induced by conditioned media from activated M1 microglia in vitro. We also show that L-cysteine promoted AMP-activated protein kinase (AMPK) activation and the AMPK inhibitor abolished these anti-apoptotic and anti-inflammatory effects of L-cysteine. Taken together, our findings demonstrate that L-cysteine-derived H2S attenuated neuronal apoptosis after HI and suggest that these effects, in part, result from enhancing microglia M2 polarization and modulating complement expression via AMPK activation.

l-Cysteine suppresses hypoxia-ischemia injury in neonatal mice by reducing glial activation, promoting autophagic flux and mediating synaptic modification via H2S formation.

We previously reported that l-Cysteine, an H2S donor, significantly alleviated brain injury after hypoxia-ischemic (HI) injury in neonatal mice. However, the mechanisms underlying this neuroprotective effect of l-Cysteine against HI insult remain unknown. In the present study, we tested the hypothesis that the protective effects of l-Cysteine are associated with glial responses and autophagy, and l-Cysteine attenuates synaptic injury as well as behavioral deficits resulting from HI. Consistent with our previous findings, we found that treatment with l-Cysteine after HI reduced early brain injury, improved behavioral deficits and synaptic damage, effects which were associated with an up-regulation of synaptophysin and postsynaptic density protein 95 expression in the lesioned cortex. l-Cysteine attenuated the accumulation of CD11b+/CD45high cells, activation of microglia and astrocytes and diminished HI-induced increases in reactive oxygen species and malondialdehyde within the lesioned cortex. In addition, l-Cysteine increased microtubule associated protein 1 light chain 3-II and Beclin1 expression, decreased p62 expression and phosphor-mammalian target of rapamycin and phosphor-signal transducer and activator of transcription 3. Further support for a critical role of l-Cysteine was revealed from results demonstrating that treatment with an inhibitor of the H2S-producing enzyme, amino-oxyacetic acid, reversed the beneficial effects of l-Cysteine described above. These results demonstrate that l-Cysteine effectively alleviates HI injury and improves behavioral outcomes by inhibiting reactive glial responses and synaptic damage and an accompanying triggering of autophagic flux. Accordingly, l-Cysteine may provide a new a therapeutic approach for the treatment of HI via the formation of H2S.

Clinical Outcomes of Cardiac Resynchronization with Epicardial Left Ventricular Lead.

BACKGROUND: Left ventricular (LV) pacing in cardiac resynchronization therapy (CRT) can be achieved via a transvenous or epicardial route. A surgically implanted epicardial LV (eLV) lead is used after a standard transvenous LV (tLV) lead implantation has failed. However, studies of clinical outcomes in patients with eLV leads and comparisons of outcome between tLV and eLV-CRT are sparse. Therefore, the purpose of this study is to compare clinical response between tLV-CRT and eLV-CRT, as well as to understand the differences within the eLV-CRT population. METHODS: Forty-four patients received eLV-CRT following unsuccessful attempts of tLV-CRT implantation between 2002 and 2013 at the University of California, San Diego (UCSD) and Mayo Clinics. These patients were matched for age, gender, and etiology of cardiomyopathy in a 1:2 ratio with a cohort of patients who received tLV-CRT during the same time period. RESULTS: During a mean follow-up of 57 months, similar clinical outcomes and survival rate were noted between tLV and eLV-CRT patients (all P > 0.05). Within the eLV-CRT group, dilated cardiomyopathy patients had significant improvement in New York Heart Association class and ejection fraction (both P < 0.05), while ischemic cardiomyopathy patients did not (both P > 0.05). eLV-CRT patients with nonanterior lead location had significantly improved survival (P < 0.001). There was also a trend for improved survival in those with nonapical lead location (P = 0.09). CONCLUSION: In this case-matched two-centered study, comparable improvements were noted in patients with tLV-CRT and eLV-CRT. Operators should target nonanterior and nonapical locations during eLV-CRT implantation. Use of eLV-CRT should be considered a viable alternative for CRT candidates.

Role of inflammation in the initiation and maintenance of atrial fibrillation and the protective effect of atorvastatin in a goat model of aseptic pericarditis.

The present study was designed to determine the association between atrial fibrillation (AF) and inflammation in a goat sterile pericarditis model and to assess the effect of atorvastatin, a cholesterol­reducing drug, on AF. A total of 15 adult male goats were randomly divided into control, untreated pericarditis and atorvastatin­treated pericarditis groups. Pericarditis was induced via thoracotomy and atorvastatin was administered orally (60 mg/day) to the goats in the latter group for the duration of the study, commencing 1 week prior to surgery. The levels of high­sensitivity C­reactive protein (hs­CRP), interleukin(IL)­6 and tumor necrosis factor­α (TNF­α) were significantly elevated following surgery in the untreated pericarditis and atorvastatin groups compared with the control group (P<0.05). However, lower levels of hs­CRP, IL­6 and TNF­α were observed in the atorvastatin group compared with the untreated pericarditis group (P<0.05). Additionally, the animals in the atorvastatin­treated pericarditis group had a longer effective refractory period (ERP) and a higher rate adaptation of the ERP compared with those in the untreated pericarditis group (P<0.05). There was a significant negative correlation between the levels of ERP and hs­CRP in the untreated pericarditis group. The inducibility of AF in the left atrium and the duration of AF in the untreated pericarditis and atorvastatin­treated groups increased significantly following surgery (P<0.05). The pericarditis group, however, had a longer duration of AF compared with the atorvastatin group (P<0.05). Thus, inflammation may promote AF by shortening atrial ERP and by reducing the rate adaptation of ERP. These results suggested that atorvastatin can attenuate AF by inhibiting inflammation and may assist in preventing the occurrence and recurrence of AF following cardiac surgery.