Latest Issue
Issue 7 ， 2020
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Epigenetic role of
N 6-methyladenosine (m6A) RNA methylation in the cardiovascular systemAbstract：As the most prevalent and abundant transcriptional modification in the eukaryotic genome, the continuous and dynamic regulation of N6-methyladenosine (m6A) has been shown to play a vital role in physiological and pathological processes of cardiovascular diseases (CVDs), such as ischemic heart failure (HF), myocardial hypertrophy, myocardial infarction (MI), and cardiomyogenesis. Regulation is achieved by modulating the expression of m6A enzymes and their downstream cardiac genes. In addition, this process has a major impact on different aspects of internal biological metabolism and several other external environmental effects associated with the development of CVDs. However, the exact molecular mechanism of m6A epigenetic regulation has not been fully elucidated. In this review, we outline recent advances and discuss potential therapeutic strategies for managing m6A in relation to several common CVD-related metabolic disorders and external environmental factors. Note that an appropriate understanding of the biological function of m6A in the cardiovascular system will pave the way towards exploring the mechanisms responsible for the development of other CVDs and their associated symptoms. Finally, it can provide new insights for the development of novel therapeutic agents for use in clinical practice.Keywords：N6-methyladenosine (m6A);RNA methylation;Cardiovascular system;Metabolic disorder- 118
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Published：2022-01-05 -
Biological pacemaker: from biological experiments to computational simulation
Abstract：Pacemaking dysfunction has become a significant disease that may contribute to heart rhythm disorders, syncope, and even death. Up to now, the best way to treat it is to implant electronic pacemakers. However, these have many disadvantages such as limited battery life, infection, and fixed pacing rate. There is an urgent need for a biological pacemaker (bio-pacemaker). This is expected to replace electronic devices because of its low risk of complications and the ability to respond to emotion. Here we survey the contemporary development of the bio-pacemaker by both experimental and computational approaches. The former mainly includes gene therapy and cell therapy, whilst the latter involves the use of multi-scale computer models of the heart, ranging from the single cell to the tissue slice. Up to now, a bio-pacemaker has been successfully applied in big mammals, but it still has a long way from clinical uses for the treatment of human heart diseases. It is hoped that the use of the computational model of a bio-pacemaker may accelerate this process. Finally, we propose potential research directions for generating a bio-pacemaker based on cardiac computational modeling.Keywords：Biological pacemaker;Gene therapy;Cell therapy;Cardiac simulation;Computational modeling- 52
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Published：2022-01-05
Review
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Multi-biomarker strategy for prediction of myocardial dysfunction and mortality in sepsis
Abstract：Objective:The present study was to evaluate the feasibility of using the multi-biomarker strategy for the prediction of sepsis-induced myocardial dysfunction (SIMD) and mortality in septic patients.Methods:Brain natriuretic peptide (BNP), cardiac troponin I (cTnI), and heart-type fatty acid-binding protein (h-FABP) in 147 septic patients were assayed within 6 h after admission. We also determined the plasma levels of myeloperoxidase (MPO) and pregnancy-associated plasma protein-A (PAPP-A). The receiver operating characteristic (ROC) curve was used to assess the best cutoff values of various single-biomarkers for the diagnosis of SIMD and the prediction of mortality. Also, the ROC curve, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) indices were used to evaluate the feasibility of using multi-biomarkers to predict SIMD and mortality.Results:Our statistics revealed that only h-FABP independently predicted SIMD (P<0.05). The addition of MPO and cTnI to h-FABP for SIMD prediction provided an NRI of 18.7% (P=0.025) and IDI of 3.3% (P=0.033). However, the addition of MPO or cTnI to h-FABP did not significantly improve the predictive ability of h-FABP to SIMD, as evidenced by the area under the curve (AUC), NRI, and IDI (all P>0.05). A history of shock and MPO were independent predictors of mortality in septic patients (both P<0.05). The addition of PAPP-A and h-FABP to MPO resulted in a mortality prediction with NRI of 25.5% (P=0.013) and IDI of 2.9% (P=0.045). However, this study revealed that the addition of h-FABP or PAPP-A to MPO did not significantly improve the ability to predict mortality, as evidenced by the AUC, NRI, and IDI (all P>0.05).Conclusions:The findings of this study indicate that a sensitive and specific strategy for early diagnosis of SIMD and mortality prediction in sepsis should incorporate three biomarkers.Keywords：Multi-biomarker;Myocardial dysfunction;Sepsis;Mortality- 73
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Published：2022-01-05 -
Role of adjuvant (chemo)radiotherapy for resected extrahepatic cholangiocarcinoma: a meta-analysis#
Abstract：Background:Adjuvant (chemo)radiotherapy (A(C)RT) may be an important supplement to surgery for extrahepatic cholangiocarcinoma (EHCC). However, whether all patients would achieve benefits from A(C)RT and which adjuvant regimen, adjuvant radiotherapy (ART) or adjuvant chemoradiotherapy (ACRT), would be preferred, are still undetermined. The low incidence of EHCC makes it difficult to carry out randomized controlled trials (RCTs); therefore, almost all clinical studies on radiotherapy are retrospective. We have conducted a meta-analysis of these retrospective studies.Methods:We conducted a meta-analysis of current retrospective studies using PubMed, Embase, and ClinicalTrials databases. All studies published in English that were related to A(C)RT and which analyzed overall survival (OS), disease-free survival (DFS), or locoregional recurrence-free survival (LRFS) were included. Estimated hazard ratios (HRs) were calculated for OS, DFS, and LRFS. Results:Data from eight studies including 685 patients were included. Our analysis showed that A(C)RT significantly improved OS (HR 0.69, 95% confidence interval (CI) 0.48–0.97, P=0.03), DFS (HR 0.60, 95% CI 0.47–0.76, P<0.0001), and LRFS (HR 0.27, 95% CI 0.17–0.41, P<0.00001) of EHCC overall. In subgroups, patients with microscopically positive resection margin (R1) could achieve a benefit from A(C)RT (HR 0.44, 95% CI 0.27–0.72, P=0.001). No statistically OS difference was observed in negative resection margin (R0) subgroup (HR 0.98, 95% CI 0.30–3.19, P=0.98).Significant OS benefit was found in patients who received concurrent ACRT (HR 0.40, 95% CI 0.26–0.62, P<0.0001), while the result of ART without chemotherapy showed no significant benefit (HR 1.14, 95% CI 0.29–4.50, P=0.85). In the distal cholangiocarcinoma subgroup, no significant difference was seen when ACRT and ART were included (HR 0.61, 95% CI 0.14–2.72, P=0.52), but a significant difference was seen when analyzing the concurrent ACRT only (HR 0.29, 95% CI 0.13–0.64, P=0.002). Conclusions:A(C)RT may improve OS, DFS, and LRFS in EHCC patients, especially in those with R1 resection margins. ACRT may be superior to ART especially in distal patients.Keywords：Adjuvant (chemo)radiotherapy;Extrahepatic cholangiocarcinoma;Meta-analysis;Disease-free survival;Overall survival- 21
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Published：2022-01-05 -
Porcine circovirus 3 capsid protein induces autophagy in HEK293T cells by inhibiting phosphorylation of the mammalian target of rapamycin
Abstract：Porcine circovirus 3 (PCV3) has been detected in major pig-producing countries around the world since its first report in the US in 2016. Most current studies have focused on epidemiological investigations and detection methods of PCV3 because of lack of live virus strains for research on its pathogenesis in porcine cells or even in pigs. We constructed a recombinant plasmid pCMV-Cap carrying the PCV3 orf2 gene to investigate the effects of capsid (Cap) protein expression on autophagic response in human embryonic kidney cell line 293T (HEK293T). We demonstrate that PCV3 Cap protein induced complete autophagy shown as formation of autophagosomes and autophagosome-like vesicles as well as LC3-II conversion from LC3-I via inhibiting phosphorylation of the mammalian target of rapamycin (mTOR) in HEK293T cells. The ubiquitin–proteasome pathway is also involved in the autophagy process. These findings provide insight for further exploration of PCV3 pathogenetic mechanisms in porcine cells.Keywords：Porcine circovirus 3 (PCV3);Capsid (Cap) protein;Autophagy- 84
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Hyaluronic acid derivative-modified nano-structured lipid carrier for cancer targeting and therapy#
Abstract：To reduce the problems of poor solubility, high in vivo dosage requirement, and weak targeting ability of paclitaxel (PTX), a hyaluronic acid-octadecylamine (HA-ODA)-modified nano-structured lipid carrier (HA-NLC) was constructed. HA-ODA conjugates were synthesized by an amide reaction between HA and ODA. The hydrophobic chain of HA-ODA can be embedded in the lipid core of the NLC to obtain HA-NLC. The HA-NLC displayed strong internalization in cluster determinant 44 (CD44) highly expressed MCF-7 cells, and endocytosis mediated by the CD44 receptor was involved. The HA-NLC had an encapsulation efficiency of PTX of 72.0%. The cytotoxicity of the PTX-loaded nanoparticle HA-NLC/PTX in MCF-7 cells was much stronger than that of the commercial preparation Taxol®. In vivo, the HA-NLC exhibited strong tumor targeting ability. The distribution of the NLCs to the liver and spleen was reduced after HA modification, while more nanoparticles were aggregated to the tumor site. Our results suggest that HA-NLC has excellent properties as a nano drug carrier and potential for in vivo targeting.Keywords：Paclitaxel (PTX);Hyaluronic acid-octadecylamine (HA-ODA);Nano-structured lipid carrier (NLC);Tumor targeting;In vivo distribution- 133
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Published：2022-01-05 -
Postprandial proximal gastric acid pocket and its association with gastroesophageal acid reflux in patients with short-segment Barrett’s esophagus
Abstract：Objective:To determine the characteristics of postprandial proximal gastric acid pockets (PPGAPs) and their association with gastroesophageal acid reflux in patients with Barrett’s esophagus (BE).Methods:Fifteen patients with BE (defined by columnar lined esophagus of ≥1 cm) and 15 healthy individuals that were matched for age, gender, and body mass index, were recruited. The fasting intragastric pH and the appearance time, length, lowest pH, and mean pH of the PPGAP were determined using a single pH electrode pull-through experiment. For BE patients, a gastroesophageal reflux disease questionnaire (GerdQ) was completed and esophageal 24-h pH monitoring was carried out.Results:The PPGAP was significantly longer (5 (3, 5) cm vs. 2 (1, 2) cm) and the lowest pH (1.1 (0.8, 1.5) vs. 1.6 (1.4, 1.9)) was significantly lower in patients with short-segment BE than in healthy individuals. The PPGAP started to appear proximally from the gastroesophageal pH step-up point to the esophageal lumen. The acidity of the PPGAP was higher in the distal segment than in the proximal segment. In short-segment BE patients, there were significant correlations between the acidity and the appearance time and length of the PPGAP. The length and acidity of the PPGAP were positively associated with gastroesophageal acid reflux episodes. The acidity of the PPGAP was associated with the DeMeester scores, the GerdQ scores, and the fasting intragastric pH.Conclusions:In patients with short-segment BE, a PPGAP is commonly seen. Its length and acidity of PPGAP are associated with gastroesophageal acid reflux, the DeMeester score, and the GerdQ score in patients with short-segment BE.Keywords：Short-segment Barrett’s esophagus;Postprandial proximal gastric acid pocket (PPGAP);Gastroesophageal acid reflux- 123
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Published：2022-01-05
Article
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Secondary manifestations of mitochondrial disorders
Abstract：Mitochondrial disorders (MIDs) are a heterogeneous group of genetic metabolic diseases due to mutations in the mitochondrial DNA (mtDNA) or in the nuclear DNA (nDNA) (Rahman and Rahman, 2018). Some affected genes encode proteins with various functions, or structural RNAs such as transfer RNAs (tRNAs) and ribosomal RNAs (rRNAs). MIDs may also be caused by mutations in non-coding regions (e.g., D-loop of mtDNA) (Rahman and Rahman, 2018). Proteins involved in MIDs include enzymes, assembling factors, transport proteins, signaling proteins, pore proteins, and fusion/fission proteins (Gorman et al., 2016). The pathways most frequently affected by mutations in “mitochondrial genes” are the respiratory chain and the oxidative phosphorylation. Dysfunction of many other pathways (e.g., β-oxidation, pyruvate-dehydrogenase complex, and heme synthesis) may also manifest as MIDs (Hu et al., 2019). The estimated prevalence of MIDs is at least 1:5000 (Ng and Turnbull, 2016).Keywords：Mitochondrial disorder;nDNA;Multiple mtDNA deletions;Phenotype;Multisystem involvement- 75
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Published：2022-01-05
Correspondence
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