[Long non-coding RNA in spermatogenesis regulation and male infertility: Progress in research].

Long non-coding RNA (lncRNA) is an RNA molecule transcribed by RNA polymerase II, longer than 200 nt, and not translated into proteins. During gonadal development and spermatogenesis, lncRNAs are involved in epigenetic mechanisms, including DNA methylation, chromatin remodeling, and histone tail modification, which play important regulatory roles at the transcriptional or post-transcriptional level. Epigenomics including lncRNA is considered to be the second dimension of DNA sequence that can be adapted to environmental factors to specifically regulate gene expressions in some cells. Based on the functional action mechanism of lncRNAs, we reviewed the advances in the studies of lncRNAs in the direction of spermatogenesis and male infertility and analyzed the potential of lncRNAs as a biomarker of male infertility. The potential application of lncRNA in the treatment of male infertility diseases can be further explored based on the lncRNA target, RNA interference, competitive binding closed target and structural disruption of lncRNAs.

CircMAP3K5 promotes cardiomyocyte apoptosis in diabetic cardiomyopathy by regulating miR-22-3p/DAPK2 Axis.

BACKGROUND: Diabetic cardiomyopathy (DCM) is one of the serious complications of the accumulated cardiovascular system in the long course of diabetes. To date, there is no effective treatment available for DCM. Circular RNA (circRNA) is a novel r2egulatory RNA that participates in a variety of cardiac pathological processes. However, the regulatory role of circular RNA MAP3K5 (circMAP3K5) in DCM is largely unclear. METHODS AND RESULTS: Microarray analysis of DCM rats' heart circular RNAs was performed and the highly species-conserved circRNA mitogen-activated protein kinase kinase kinase 5 (circMAP3K5) was identified, which participates in DCM processes. High glucose-provoked cardiotoxicity leads to the up-regulation of circMAP3K5, which mechanistically contributes to cardiomyocyte cell death. Also, in high glucose-induced H9c2 cardiomyocytes, the level of apoptosis was significantly increased, as well as the expression of circMAP3K5. In contrast, the depletion of circMAP3K5 could reduce high glucose-induced apoptosis in cardiomyocytes. In terms of mechanism, circMAP3K5 acts as a miR-22-3p sponge and miR-22-3p directly target death-associated protein kinase 2 (DAPK2) in H9c2 cardiomyocytes, where in circMAP3K5 upregulates DAPK2 expression by targeting miR-22-3p. Moreover, we also found that miR-22-3p inhibitor and pcDNA DAPK2 could antagonize the protective effects brought by the depletion of circMAP3K5. CONCLUSION: CircMAP3K5 is a highly conserved noncoding RNA that is upregulated during DCM process. We concluded that circMAP3K5 promotes high glucose-induced cardiomyocyte apoptosis by regulating the miR-22-3p/DAPK2 axis. The results of this study highlight a novel and translationally important circMAP3K5-based therapeutic approach for DCM.

Combined treatment of ulinastatin and tranexamic acid provides beneficial effects by inhibiting inflammatory and fibrinolytic response in patients undergoing heart valve replacement surgery.

OBJECTIVE: To investigate the effect of ulinastatin and tranexamic acid administered alone or in combination on inflammatory cytokines and fibrinolytic system in patients undergoing heart valve replacement surgery during cardiopulmonary bypass (CPB). BACKGROUND: CPB-induced fibrinolytic hyperfunction and systemic inflammatory response syndrome (SIRS) are the leading causes responsible for the occurrence of postsurgical complications such as postsurgical cardiac insufficiency and lung injury, which may lead to an increase in postsurgical bleeding, prolongation of hospital stay, and increased costs. METHODS: One hundred twenty patients undergoing heart valve replacement surgery during CPB were randomly assigned into 4 groups of 30 patients each: blank control group (Group C), tranexamic acid group (Group T), ulinastatin group (Group U), and tranexamic acid-ulinastatin combination group (Group D). Physiological saline, tranexamic acid, ulinastatin, and a combination of tranexamic acid and ulinastatin were given to each group, respectively. Arterial blood was collected from the radial artery at 4 time points: after induction of anesthesia (T1), unclamping the ascending aorta (T2), and at 1 hour (T3) and 24 hours (T4) after CPB. The levels of plasma tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), neutrophil elastase (NE), and the concentrations of tissue plasminogen activator (t-PA) and α2-antiplasmin (α2-AP) were detected. The changes in the volume of pericardial mediastinal drainage after surgery were observed and recorded. RESULTS: The plasma TNF-α, IL-6, and NE levels significantly increased in patients from all 4 groups at time points of T2, T3, and T4 in comparison to those before CPB (P < .05), and the plasma TNF-α and IL-6 levels in groups U and D were significantly lower than those in the other 2 groups (P < .05). The plasma t-PA, α2-AP, and D-dimer concentrations significantly increased in patients from all 4 groups at T2 and T3 compared with those before CPB (P < .05), and the plasma t-PA and D-dimer concentrations were significantly lower in groups T and D than those in groups U and C (P < .05) at T2 and T3. The plasma α2-AP concentrations in groups T and D were significantly higher than those in Group C at T3 (P < .05). The volumes of pericardial mediastinal drainage per body surface area were significantly lower in groups T and D than those in Group C 6 hours after the surgery (P < .05). CONCLUSIONS: Ulinastatin inhibits the release of inflammatory medium and reduces the inflammatory response during CPB. Tranexamic acid can effectively inhibit the fibrinolytic hyperfunction caused by CPB and thus decreases postsurgical bleeding. In addition, it exhibits a minor anti-inflammatory response. As a consequence, a combined treatment of ulinastatin and tranexamic acid reduces postsurgical bleeding and shortens postoperative hospital stay in patients undergoing heart valve replacement surgery.

A Model of Long-Term Ventricular Fibrillation in Isolated Rat Hearts.

Ventricular fibrillation (VF) is a fatal arrhythmia with a high incidence in cardiac patients, but VF arrest under perfusion is a neglected method of intraoperative arrest in the field of cardiac surgery. With recent advances in cardiac surgery, the demand for prolonged VF studies under perfusion has increased. However, the field lacks simple, reliable, and reproducible animal models of chronic ventricular fibrillation. This protocol induces long-term VF through alternating current (AC) electrical stimulation of the epicardium. Different conditions were used to induce VF, including continuous stimulation with a low or high voltage to induce long-term VF and stimulation for 5 min with a low or high voltage to induce spontaneous long-term VF. The success rates of the different conditions, as well as the rates of myocardial injury and recovery of cardiac function, were compared. The results showed that continuous low-voltage stimulation induced long-term VF and that 5 min of low-voltage stimulation induced spontaneous long-term VF with mild myocardial injury and a high rate of recovery of cardiac function. However, the low-voltage, continuously stimulated long-term VF model had a higher success rate. High-voltage stimulation provided a higher rate of VF induction but showed a low defibrillation success rate, poor recovery of cardiac function, and severe myocardial injury. On the basis of these results, continuous low-voltage epicardial AC stimulation is recommended for its high success rate, stability, reliability, reproducibility, low impact on cardiac function, and mild myocardial injury.

Efficacy, safety, and economy of shensongyangxin capsules for the treatment of coronary heart disease arrhythmia: a meta-analysis of randomized controlled trials.

Background: Shensong Yangxin Capsules (SSYX) is a proprietary Chinese medicine commonly, used in the treatment of arrhythmia. In recent years, a flurry of randomized controlled trials of SSYX was reported in the treatment of Coronary heart disease arrhythmia in China. However, these experiments have not been systematically evaluated by economics. The purpose of this study was to assess the efficacy, safety, and economy of the SSYX in the treatment of arrhythmia in patients with coronary heart disease. Methods: With "Shensong Yangxin Capsules" "Coronary Heart Disease" "Coronary Atherosclerotic Heart Disease"and "Arrhythmia" as the subject words, the relevant journals and conference papers were searched manually in China National Knowledge Infrastructure (CNKI), Wanfang Database, VIP, PubMed, Web Of Science, CBM, Embase and The Cochrane Library. The literature of randomized controlled trials of SSYX in the treatment of coronary heart disease arrhythmia was searched until November 2022. All data were analyzed using RevMan 5.3 Sotware and combined with cost-effectiveness for economic evaluation. Results: Twenty randomized controlled trials were included in this study, with a total of 2011 cases. The meta-analysis showed that the therapeutic effect of SSYX-metoprolol is superior to that of metoprolol alone. SSYX is superior to amiodarone in improving the total clinical effective rate, reducing the incidence of adverse reactions, and reducing the junction premature beats. There was no significant difference between the SSYX and amiodarone in the curative effect of ECG, ventricular premature complexes, and atrial premature beats. The results of pharmacoeconomics show that SSYX has a cost-effectiveness advantage in treating coronary heart disease arrhythmia. Single-factor sensitivity analysis also confirmed the stability of the results. In summary, SSYX has a curative effect, safety, and economy in treating coronary heart disease arrhythmia.

Human umbilical cord-derived stem cell sheets improve left ventricular function in rat models of ischemic heart failure.

INTRODUCTION: Human umbilical cord-derived mesenchymal stem cells (UC-MSCs) are among the most promising cell therapy sources used to treat ischemic heart disease. Cell sheet engineering has been used to transplant stem cells and improve their therapeutic effectiveness. We aimed to evaluate the effectiveness of UC-MSC sheets in the treatment of chronic ischemic heart failure. METHODS AND RESULTS: Flow cytometric analysis showed that UC-MSCs were positive for CD73, CD90, and CD105. UC-MSC sheets were produced from UC-MSCs using temperature-responsive culture dishes. Afterward, these sheets were transplanted onto the epicardial surface at the infarct heart in rat models of chronic ischemic heart failure. At four weeks after the transplantation, echocardiography analysis revealed that the cardiac function of the UC-MSC sheets group was significantly better than that of the suspension and myocardial infarction (MI) only groups. Furthermore, histological examinations revealed that the left ventricular remodeling was attenuated compared with the suspension and MI-only groups. In the UC-MSC slice group, the neovascular den and cell size in the infarct margin region were was significantly improved than in the suspension and MI-only groups. Also, the UC-MSC sheets inhibited the PI3K/AKT/mTOR signaling pathway in chronic ischemic heart failure. CONCLUSIONS: UC-MSC sheets can maintain cardiac function and attenuate ventricular remodeling in chronic ischemic heart failure, indicating that this strategy would be a promising therapeutic option in the clinical scenario.

Sevoflurane postconditioning protects isolated rat hearts against ischemia-reperfusion injury: the role of radical oxygen species, extracellular signal-related kinases 1/2 and mitochondrial permeability transition pore.

The roles of reactive oxygen species (ROS), extracellular signal-regulated kinase 1/2 (ERK 1/2) and mitochondrial permeability transition pore (mPTP) in sevoflurane postconditioning induced cardioprotection against ischemia-reperfusion injury in Langendorff rat hearts were investigated. When compared with the unprotected hearts subjected to 30 min of ischemia followed by 1 h of reperfusion, exposure of 3% sevoflurane during the first 15 min of reperfusion significantly improved functional recovery, decreased infarct size, reduced lactate dehydrogenase and creatine kinase-MB release, and reduced myocardial malondialdehyde production. However, these protective effects were abolished in the presence of either ROS scavenger N-acetylcysteine or ERK 1/2 inhibitor PD98059, and accompanied by prevention of ERK 1/2 phosphorylation and elimination of inhibitory effect on mPTP opening. These findings suggested that sevoflurane postconditioning protected isolated rat hearts against ischemia-reperfusion injury via the recruitment of the ROS-ERK 1/2-mPTP signaling cascade.

[The empirical study on paracrine communication of bone marrow mesenchymal stem cells].

OBJECTIVE: To study the influence of (60)Co gamma exposure on paracrine effect of marrow mesenchymal stem cells (MSC). To evaluate the function and construction after early stage of acute myocardial infarction (AMI) by injection of supernatant liquid. To discuss the mechanism of prarcrine communication initially. METHODS: MSC were radiated by (60)Co gamma with different dosage. The culture solution was collected peri-irradiation. The changes of Vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), Interleuki-1beta (IL-1beta) in supernatant liquid were checked by ELISA. Using a rat model of AMI, the supernatant liquid and control medium were injected intramyocardially and intraperitoneally according to the project. After 4 weeks, the cardiac dimension and functions were assessed, the microvessel density were detected. RESULTS: Three cytokines decreased significantly after irradiation, with the increasing in dosage of irradiation, the secretory volume of cytokines decreased greatly. When compared with the control group (group A 6.6 +/- 0.6) and medium group (group C 5.7 +/- 0.7), the microvessel density in supernatant liquid group (group B 10.8 +/- 2.9) increased obviously, contributing to improvement in cardiac function and dimension. (Left ventricular internal dimension in diastolic (LVDd) postoperation: A 8.1 mm +/- 1.5 mm, B 7.0 mm +/- 1.5 mm, C 7.7 mm +/- 1.1 mm; Eject fraction (EF) postoperation: A 43.8% +/- 8.9%, B 51.5% +/- 7.8%, C 45.6% +/- 8.1%. CONCLUSIONS: (60)Co gamma radiation exposure can degrade MSC' ability of paracrine communication. The paracrine effect which should take important role in improving the cardiac function after AMI. The mechanism of prarcrine is complex, neovascularization is the important link.

Toxic element (As and Hg) content and health risk assessment of commercially available rice for residents in Beijing based on their dietary consumption.

Arsenic (As) and mercury (Hg) are toxic elements that are often classified as heavy metals, much like cadmium (Cd) and lead (Pb) and others. In this study, we determined the As and Hg contents in rice samples obtained from commercially available rice in Beijing and the health risks associated with daily dietary exposure to As and Hg by the consumption of this rice. Furthermore, the pollution levels of the rice were evaluated based on the Nemerow index. For this purpose, we collected 353 rice samples from 16 municipal districts in Beijing and determined the As and Hg contents in these samples by microwave digestion and inductively coupled plasma mass spectrometry (ICP-MS). The results were as follows: (i) the average content of As in the collected rice samples was 154.91 µg/kg (95% confidence interval (CI) of 139.90-169.92 µg/kg), and the average content of Hg was 2.02 µg/kg (95% CI of 1.25-2.79 µg/kg), which did not exceed the limits established by China's National Standard; (ii) the Nemerow index indicated that the As and Hg contents in these rice samples were safe; (iii) the dietary exposure to As and Hg by rice consumption was, respectively, 15.35 µg/day and 0.20 µg/day, which accounted for 12.91% and 3.35% of the total dietary exposure, respectively; (iv) the hazard quotients (HQs) of As and Hg by the dietary consumption of rice were, respectively, 0.77 and 0.03, and both the HQ and hazard index (HI is 0.8) were less than one. These results indicate that dietary exposure to As and Hg would have no detrimental effect on the health of the residents in the study area; however, the possible carcinogenesis by As in these residents warrants serious attention.

Epidemiological and clinical characteristics of 3327 cases of traffic trauma deaths in Beijing from 2008 to 2017: a retrospective analysis.

We investigated the epidemiological and clinical characteristics deaths from road traffic injury (RTI) in Beijing, and provided evidence useful for the prevention of fatal traffic trauma and for the treatment of traffic-related injuries.We retrospectively reviewed death cases provided by the Beijing Red Cross Emergency Center on road traffic injury deaths from 2008 to 2017. We analyzed population characteristics, time distribution, distribution of transportation modes, intervals to death, locations and injured body parts.From 2008 to 2017, there were 3327 deaths from RTI recorded by the Beijing Red Cross Emergency Center, with mainly males among these deaths. The average age at death was 46.19 ±â€Š17.43 years old (46.19, 0.43-100.24). In accidents with more detail recorded, pedestrians and people using nonmotorized transportation modes suffered the most fatalities (664/968, 68.60%). The most commonly injured body parts were the head (2569/3327, 77.22%), followed by the chest (180/3327, 5.41%), abdomen (130/3327, 3.91%), lower extremities (68/3327, 2.04%), pelvis (67/3327, 2.01%), spinal cord (31/3327, 0.93%), and upper extremities (26/3327, 0.78%). Burns accounted for 0.96% (32/3327), and unknown body parts were affected in 11.28% (365/3327). The average time interval from injury to death was 36.90 ±â€Š89.57 h (36.90, 0-720); 46.7% (1554/3327) died within 10 minutes after injury; 9.02% (300/3327) died between 10 min and 1 hour; 30.33% (1009/3327) died between 1 hour and 3 days; 13.95% (464/3327) died between 3 and 30 days.In Beijing, RTI is a significant cause of preventable death, particularly among pedestrians and users of non-motorized vehicles. Head trauma was the most lethal cause of RTI deaths. Our findings suggested that interventions to prevent collisions and reduce injuries, and improved trauma treatment process and trauma rescue system could address a certain proportion of avoidable RTI deaths.

Sevoflurane postconditioning protects chronically-infarcted rat hearts against ischemia-reperfusion injury by activation of pro-survival kinases and inhibition of mitochondrial permeability transition pore opening upon reperfusion.

We evaluated the cardioprotection against myocardial ischemia-reperfusion injury induced by sevoflurane postconditioning (SpostC) in chronically-infarcted rat hearts, and investigated the roles of phosphoinositide 3-kinase (PI3K)-protein kinase B/Akt (PKB/Akt), mitogen-activated extracellular regulated kinase 1/2 (MEK 1/2)-extracellular regulated kinase 1/2 (ERK 1/2), and mitochondrial permeability transition pore (mPTP). Left anterior descending (LAD) coronary artery was ligated to induce myocardial infarction in rats. Six weeks later, chronically-infarcted hearts were isolated and subjected to 30 min of global ischemia, followed by 1 h of reperfusion with Krebs-Henseleit (K-H) buffer. SpostC was administered by perfusing the hearts with K-H buffer saturated with 3% sevoflurane during the first 15 min of reperfusion. To evaluate the role of PI3K-PKB/Akt and MEK 1/2-ERK 1/2 in SpostC, PI3K inhibitor LY294002 (15 microM) and MEK 1/2 inhibitor PD98059 (20 microM) were administered alone or together with sevoflurane during the first 15 min of reperfusion. We found that exposure of 3% sevoflurane during early reperfusion significantly improved functional recovery (improved left ventricular developed pressure (LVDP), +/-dp/dt, CF, HR and reduced left ventricular end-diastolic pressure (LVEDP)), decreased myocardial infarct size and reduced LDH and CK-MB release, when compared with unprotected hearts. However, these protective effects were abolished in the presence of either LY294002 or PD98059, which was accompanied by the prevention of PKB/Akt and ERK 1/2 phosphorylation, and reduction of myocardial nicotinamide adenine dinucleotide (NAD+) content. These findings suggest that sevoflurane postconditioning protects chronically-infarcted rat hearts against ischemia-reperfusion injury by inhibiting mPTP opening via recruitment of PKB/Akt and ERK 1/2.

Reconstruction of the architecture of ventricular myocardial fibers in ex vivo human hearts.

BACKGROUND: The 3-dimensional arrangement of the ventricular mass has been controversial. The aim of the present study was to investigate the macroarchitecture of ventricular myocardial fibers and to analyze whether it is consistent with the helical ventricular myocardial band (HVMB) hypothesis. METHODS: Eight excised human hearts were scanned by diffusion tensor magnetic resonance imaging (DT-MRI). Fiber tracking was then used with the DT-MRI data to reconstruct and visualize the positions of the myocardial fibers to reveal the architecture of ventricular myocardial fibers. RESULTS: The left ventricular myocardial fibers were found to consist of 2 crossed populations that were approximately normal from the epicardium to the endocardium in the tangent plane. The myocardial fibers in the middle of the myocardium had a smooth, linear angular rotation. The ventricular myocardial fibers maintained complete continuity and specific orientations that corresponded to the HVMB structure. CONCLUSIONS: The architecture of the ventricular myocardial fibers in the human heart conforms to the HVMB structural hypothesis.

Investigation on the structure of ventricular mass using magnetic resonance diffusion tensor imaging.

OBJECTIVE: The 3-dimensional arrangement of the ventricular mass remains controversial. In this study, we used magnetic resonance diffusion tensor imaging (MRDTI) in an attempt to determine whether the ventricular mass is arranged in the form of a helical ventricular myocardial band (HVMB) and what the geometrical features of the HVMB are in postmortem pig hearts. MATERIALS AND METHODS: Ten pig hearts were harvested from the slaughterhouse, and their whole-body MR images were obtained. The data were obtained via DTI by single-shot echo planar imaging and sensitivity encoding. The pig hearts were scanned with single-shot echo planar imaging and sensitivity-encoding scans (TE/TRZ78.5/10000 ms) with diffusion-sensitized gradients (b = 800 s/mm2) along 6 directions. Color-coded imaging and fiber-tracking techniques were used to investigate the arrangement of the fibers of ventricular mass on a GE Healthcare Advantage Workstation (Microsoft Windows). RESULTS: Color-coded images showed that the ventricular wall in each section was uniformly divided into 3 layers (subendocardial, middle, and subepicardial) in all samples. Fiber tracking showed that the subendocardial layer ran obliquely from base to apex, turned a circle, and transformed into the middle layer at the apex, and then ran obliquely upward. The ventricular mass was arranged in the form of double-helical coils. The crossing angle between subendocardial layer and middle layer was nearly vertical. CONCLUSION: Results of our investigation with MRDTI support the theory of Torrent-Guasp et al that the ventricular mass is arranged in the form of an HVMB.

Effect of subzero-balanced ultrafiltration on postoperative outcome of patients after cardiopulmonary bypass.

OBJECTIVE: To evaluate the effect of a new ultrafiltration technique - subzero-balanced ultrafiltration technique - on early postoperative outcomes of adult patients undergoing cardiac operations with cardiopulmonary bypass. METHODS: A total of 120 patients who required cardiopulmonary bypass for cardiac surgery were randomized into two groups, 60 in each group. Patients in the treatment group received subzero-balanced ultrafiltration during cardiopulmonary bypass, while patients in the control group received routine cardiopulmonary bypass. Postoperative outcomes, including hospital mortality and morbidity of the two groups, were analyzed. RESULTS: Hospital mortality was 0% (0 of 60) in the treatment group versus 1.8% (1 of 60) in the control group (P=1.000). Total hospital complications was lower in the treated patients (11 of 60 [18.3%] versus 22 of 60 [36.7%], P=0.025). Duration of intubation time was shorter and transfusion volume within 24 hours postoperatively was less in patients having received subzero-balanced ultrafiltration during cardiopulmonary bypass (14.35 + or - 1.66 versus 18.64 + or - 1.57 h, P=0.036 and 1.54 + or - 1.56 versus 3.64 + or - 2.67 U/patient, P=0.032). Length of stay on the intensive care unit, duration of hospital stay, need for infusion of inotropic agent and drainage volumes within 24 h postoperatively between the two groups were comparable. CONCLUSIONS: Subzero-balanced ultrafiltration during cardiopulmonary bypass can effectively decrease the patients' hospital morbidity and the volume of blood transfusion: it also may promote early postoperative recovery of patients. Routine application of subzero-balanced ultrafiltration during adult cardiac operations should not be necessary, but the technique should be compared to other techniques, e.g. MUF, in further studies.

Information Diffusion on Social Media During Natural Disasters.

Social media analytics has drawn new quantitative insights of human activity patterns. Many applications of social media analytics, from pandemic prediction to earthquake response, require an in-depth understanding of how these patterns change when human encounter unfamiliar conditions. In this paper, we select two earthquakes in China as the social context in Sina-Weibo (or Weibo for short), the largest Chinese microblog site. After proposing a formalized Weibo information flow model to represent the information spread on Weibo, we study the information spread from three main perspectives: individual characteristics, the types of social relationships between interactive participants, and the topology of real interaction networks. The quantitative analyses draw the following conclusions. First, the shadow of Dunbar's number is evident in the "declared friends/followers" distributions, and the number of each participant's friends/followers who also participated in the earthquake information dissemination show the typical power-law distribution, indicating a rich-gets-richer phenomenon. Second, an individual's number of followers is the most critical factor in user influence. Strangers are very important forces for disseminating real-time news after an earthquake. Third, two types of real interaction networks share the scale-free and small-world property, but with a looser organizational structure. In addition, correlations between different influence groups indicate that when compared with other online social media, the discussion on Weibo is mainly dominated and influenced by verified users.

Adenoviral gene transfer of sphingosine kinase 1 protects heart against ischemia/reperfusion-induced injury and attenuates its postischemic failure.

Sphingosine kinase 1 (SPK1) has been identified as a central mediator of ischemia preconditioning and plays a protective role in ischemia/reperfusion (I/R)-induced cardiomyocyte death. In the present study, we investigated the protective effect of adenovirus-mediated SPK1 gene (Ad-SPK1) transfer on I/R-induced cardiac injury, and evaluated its therapeutic action on postinfarction heart failure. Cardiac SPK1 activity was increased about 5-fold by injection of Ad-SPK1, compared with injection of adenovirus carrying the green fluorescent protein gene (Ad-GFP). A more potent performance and a lower incidence of arrhythmia were observed in Ad-SPK1-injected hearts during the reperfusion period, compared with Ad-GFP-injected hearts. An enzymatic activity assay showed that creatine kinase release was also less in Ad-SPK1-injected hearts. To investigate the therapeutic action of the SPK1 gene on postischemic heart failure, the left anterior descending branch of the coronary artery in Wistar rats was ligated after direct intramyocardial injection of Ad-SPK1 or Ad-GFP as a control. Ad-SPK1 injection significantly preserved cardiac systolic and diastolic function, as evidenced by left ventricular (LV) systolic pressure, LV end-diastolic pressure, and peak velocity of contraction (dP/dt). The LV morphometric parameters of Ad-SPK1-treated animals were also preserved. In addition, SPK1 gene delivery significantly enhanced angiogenesis and reduced fibrosis. These results demonstrate that adenovirus-mediated SPK1 gene transfer could efficiently prevent I/R-induced myocardial injury and attenuate postischemic heart failure. Thus, SPK1 gene delivery would be a novel strategy for the treatment of coronary heart disease.

[The experimental studies on cell transplantation into chronic ischemic myocardium using mesenchymal stem cells modified by recombinant adenovirus carrying vascular endothelial growth factors 165 gene].

OBJECTIVE: To observe the therapeutic effect of vascular endothelial growth factors 165 (VEGF165) gene expressing mesenchymal stem cells (MSCs) in chronic myocardial infarction model by providing enhanced cardioprotection, followed by angiogenic effects in infarcted myocardium. METHODS: Recombinant adenovirus vector carrying VEGF165 gene (rAd-VFGF165) was constructed. MSCs were harvested through gradient centrifugation, then were cultivated, multiplied and expanded. Recombinant adenoviruses mediated VEGF165 gene were transfected into MSCs, and the MSCs were labelled by DAPI. The left anterior descending branch of rabbits were ligated to establish a myocardial infarction model; and the animals survived for 6 weeks were randomly divided into three groups: VEGF165-expressing MSCs transplanted (Group I), MSCs transplanted (Group II) and dulbecco modified eagles medium injected (Group III). At 4 weeks after cell transplantation, the MSCs were detected by DAPI staining in infarcted region. The cardiac functions were estimated by UCG. The microvascular density in infarcted area were estimated through CD34 immunohistochemical analysis. RESULTS: Four weeks after cell transplantation, ejection fraction, E wave/A wave ratio and capillary density of the infarcted region were most improved in Group I compared with Group II and control group (P < 0.05). DAPI positive cells were most increased in Group I. CONCLUSIONS: The transplantation of VEGF165-expressing MSCs had a better therapeutic effect than the transplantation of simplex MSCs. This combined strategy of MSCs transplantation with vgene therapy could be a useful therapy for the treatment of myocardial infarction.

CXCL10/IP-10 Neutralization Can Ameliorate Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome in Rats.

The role of C-X-C motif chemokine 10 (CXCL10), a pro-inflammatory factor, in the development of acute respiratory distress syndrome (ARDS) remains unclear. In this study, we explored the role of CXCL10 and the effect of CXCL10 neutralization in lipopolysaccharide (LPS)-induced ARDS in rats. The expression of CXCL10 and its receptor chemokine receptor 3(CXCR3) increased after LPS induction. Moreover, neutralization of CXCL10 ameliorated the severity of ARDS by reducing pulmonary edema, inhibiting the release of inflammatory mediators (IFN-γ, IL-6 and ICAM-1) and limiting inflammatory cells (neutrophils, macrophages, CD8+ T cells) influx into the lung, with a reduction in CXCR3 expression in neutrophils and macrophages. Therefore, CXCL10 could be a potential therapeutic target in LPS-induced ARDS.

Differential effects of lysophosphatidylcholine and ACh on muscarinic K(+),non-selective cation and Ca(2+) currents in guinea-pig atrial cells.

We compared the effects of lysophosphatidylcholine (LPC) and acetylcholine (ACh) on IK(ACh), ICa and a non-selective cation current (INSC) in guinea-pig atrial myocytes to clarify whether LPC and ACh activate similar Gi/o-coupled effector systems.　IK(ACh), ICa and INSC were analyzed in single atrial myocytes by the whole cell patch-clamp.　LPC induced INSC in a concentration-dependent manner in atrial cells.　ACh activated IK(ACh), but failed to evoke INSC.　LPC also activated IK(ACh) but with significantly less potency than ACh.　The effects of both ligands on IK(ACh) were inhibited by intracellular loading of pre-activated PTX.　This treatment also inhibited LPC-induced INSC, indicating that IK(ACh) and INSC induced by LPC are both mediated by Gi/o.　LPC and ACh had similar potencies in inhibiting ICa, which was pre-augmented by forskolin, indicating that LPC and ACh activate similar amounts of α-subunits of Gi/o.　The different effects of LPC and ACh on IK(ACh) and INSC may suggest that LPC and ACh activate Gi/o having different types of ßγ subunits, and that LPC-induced INSC may be mediated by ßγ subunits of Gi/o, which are less effective in inducing IK(ACh).

Pharmacology of Na+/Ca2+ exchanger.

KB-R7943 inhibits the Na(+)/Ca(2+) exchanger in an independent manner or in a manner dependent on the direction of the current. This effect may be due to the experimental protocols bawed on the competition between the drug and external substrate ions. Some antiarrhythmic drugs inhibit NCX. A new column of NCX was added in Sicilian Gambit.