Abstract Background : Cardiac arrest (CA) is a leading cause of death worldwide. Even after successful cardiopulmonary resuscitation (CPR), the majorities of survivals are companied with permanent myocardial and cerebral injury. Hydrogen sulfide (H 2 S) has been recognized as a novel gasotransmitter exerting multiple organ protection; however, the lacks of ideal H 2 S donors which can controlled release H 2 S to targeted organs such as heart and brain limits its application. Results : This work utilized mesoporous iron oxide nanoparticle (MION) as the carriers of diallyl trisulfide (DATS), with polyethylene glycol (PEG) and lactoferrin (LF) modified to MIONs to acquire the prolonged circulation time and brain-targeting effects, and a novel targeted H 2 S releasing system was constructed ( DATS@MION-PEG-LF ), which exhibited excellent biocompatibility, controlled-releasing H 2 S pattern, heart and brain targeting features, and the ability to be non-invasive traced by magnetic resonance imaging. DATS@MION-PEG-LF presented potent protective effects against cerebral and cardiac ischemic injury after CA in both in vitro hypoxia/reoxygenation models and in vivo CA/CPR models, which mainly involves anti-apoptosis, anti-inflammatory and anti-oxidant mechanisms. Accordingly, the cardiac and cerebral functions were obviously improved after CA/CPR, with potentially improved survival. Conclusions : The present work provides a unique platform for targeted controlled release of H 2 S based on MIONs, and offers a new method for combinational myocardial and cerebral protection from ischemic injury, bringing considerable benefits for CA patients.
Signal transduction has been acknowledged to be involved in various cell biological processes. And it is proved that multiple signaling pathways have been associated with the development and progression of pancreatic cancer, which remains one of the most devastating human diseases. Newly developed drugs targeting these aberrant signaling pathways show bright prospect in improving the therapeutic efficacy and outcome for patients with pancreatic cancer. Here we overview the pancreatic cancer related signaling pathway disorders and the corresponding promising targeted therapeutic regimens. Keywords: Pancreatic cancer, signal transduction pathway, therapy.
Objective Despite substantial advances in surgical practice, the management of patients with impaired left ventricular ejection fraction (LVEF) remains challenging. Furthermore, evidence on the outcomes of off-pump coronary artery bypass (OPCAB) surgery in this population is inconsistent. We conducted the present study to compare the short- and long-term outcomes of OPCAB in patients with different ejection fractions. Methods This retrospective cohort study used data from the Hua-Shan Cardiac Surgery and included consecutive patients aged ≥ 18 years who underwent OPCAB procedures during 2016–2019. The patients included in the study were followed up until death or the end of data collection. Patients with different ejection fractions were matched 1:2 using propensity score matching. Factors associated with short-term outcomes were determined using logistic regression, and Kaplan–Meier survival analyses for the differences in all-cause death were generated. Results The two propensity score matched groups consisted of 40 left ventricular dysfunction (LVD) and 80 normal left ventricular function (NLVF) patients. No significant intergroup differences were observed in the postoperative outcomes for the occurrence of left heart failure (22.5% in LVD vs. 5.0% in NLVF, p = .009). Age (odds ratio = 1.11, 95% confidence interval = 1.04–1.18) but not the preoperative LVEF was shown to be a strong predictor of short-term events in logistic regression analyses. Kaplan–Meier curves displayed similar freedom from all-cause death (p = .119) or cardio-death (p = .092) between groups. Conclusion The immediate postoperative outcomes and long-term outcomes were similar between the groups, indicating that OPCAB is a safe and effective choice for patients with LVD.
Cancer metastasis is the main cause of mortality in cancer patients. However, the drugs targeting metastasis processes are still lacking, which is partially due to the short of effective in vitro model for cell invasion studies. The traditional 2-D culture method cannot reveal the interaction between cells and the surrounding extracellular matrix during invasion process, while the animal models usually are too complex to explain mechanisms in detail. Therefore, a precise and efficient 3-D in vitro model is highly desirable for cell invasion studies and drug screening tests.Precise micro-fabrication techniques are developed and integrated with soft hydrogels for constructing of 3-D lung-cancer micro-environment, mimicking the pulmonary gland or alveoli as in vivo.A 3-D in vitro model for cancer cell culture and metastasis studies is developed with advanced micro-fabrication technique, combining microfluidic system with soft hydrogel. The constructed microfluidic platform can provide nutrition and bio-chemical factors in a continuous transportation mode and has the potential to form stable chemical gradient for cancer invasion research. Hundreds of micro-chamber arrays are constructed within the collagen gel, ensuring that all surrounding substrates for tumor cells are composed of natural collagen hydrogel, like the in vivo micro-environment. The 3-D in vitro model can also provide a fully transparent platform for the visual observation of the cell morphology, proliferation, invasion, cell-assembly, and even the protein expression by immune-fluorescent tests if needed. The lung-cancer cells A549 and normal lung epithelial cells (HPAEpiCs) have been seeded into the 3-D system. It is found out that cells can normally proliferate in the microwells for a long period. Moreover, although the cancer cells A549 and alveolar epithelial cells HPAEpiCs have the similar morphology on 2-D solid substrate, in the 3-D system the cancer cells A549 distributed sparsely as single round cells on the extracellular matrix (ECM) when they attached to the substrate, while the normal lung epithelial cells can form cell aggregates, like the structure of normal tissue. Importantly, cancer cells cultured in the 3-D in vitro model can exhibit the interaction between cells and extracellular matrix. As shown in the confocal microscope images, the A549 cells present round and isolated morphology without much invasion into ECM, while starting from around Day 5, cells changed their shape to be spindle-like, as in mesenchymal morphology, and then started to destroy the surrounding ECM and invade out of the micro-chambers.A 3-D in vitro model is constructed for cancer cell invasion studies, combining the microfluidic system and micro-chamber structures within hydrogel. To show the invasion process of lung cancer cells, the cell morphology, proliferation, and invasion process are all analyzed. The results confirmed that the micro-environment in the 3-D model is vital for revealing the lung cancer cell invasion as in vivo.
Despite great advances in surgeries, the management of patients with impaired left ventricular ejection fraction is still challenging. Furthermore, evidences on outcomes of off-pump coronary artery bypass surgery (OPCAB) in this population are inconsistent. We conducted present study to compare the short and long-term outcomes in patients with different ejection fractions undertaken OPCAB.
Summary Introduction To investigate the cardioprotective effect of Micro RNA ‐21 (miR‐21) in murine myocardial infarction ( MI ). Methods Forty C57 BL /6 male mice were divided into sham group, MI group, LV ‐ GFP group, and miR‐21 group. Mice in the MI group, LV ‐ GFP group, and miR‐21 group were subjected to MI by left anterior descending artery ( LAD ) ligation, while chest was opened/closed without ligation in sham group. In MI group, expression of miR‐21 in the MI area and its surrounding areas was detected at 1st, 2nd, and 4th week after experiment. Subsequently, lentivirus expressing miR‐21 and lentivirus that did not express miR‐21 were transfected into mice left ventricular cavity of miR‐21 group and LV ‐ GFP group, respectively. Cardiac function, MI size, miR‐21 expression, collagen I level, fibronectin content, number of α ‐ SMA ‐positive cells, number of apoptotic cells, apoptosis‐related factors were compared between the three groups. Results Compared with sham group, miR‐21 levels in MI group were significantly decreased in the 1st week and 2nd week, but were almost the same in the 4th week. Left ventricular fractional shortening ( LVFS ) and left ventricular ejection fraction ( LVEF ) in the miR‐21 group improved compared to the LV ‐ GFP group. In miR‐21 group, myocardial infarct size reduced by 36.9% in comparison with LV ‐ GFP group. Compared to sham group, miR‐21 expression in the miR‐21 group and LV ‐ GFP group decreased significantly. In the miR‐21 group, collagen I level, fibronectin content and number of α ‐ SMA ‐positive cells of miR‐21 decreased significantly compared to the LV ‐ GFP group. The number of apoptotic cells in the MI areas of the miR‐21 group was significantly less than the LV ‐ GFP group. Compared with the LV ‐ GFP group, Bcl‐2 level and the ratio of Bcl‐2 to Bax were significantly increased, and the levels of Bax and Caspase‐3 decreased. Conclusions Our results suggest miR‐21 is an important regulatory molecule in the pathophysiology of MI .
Abstract Hydrogen sulfide exists widely in mammalian tissues and plays a vital role in physiological and pathophysiological processes. However, striking differences with orders of magnitude were observed for the detected hydrogen sulfide concentrations in biological matrices among different measurements in literature, which lead to the uncertainty for examination the biological relevance of hydrogen sulfide. Here, we developed and validated a liquid chromatography- mass spectrometry (LC-MS/MS) method for the determination of hydrogen sulfide in various biological matrices by determination of a derivative of hydrogen sulfide and monobromobimane named sulfide dibimane (SDB). 36 S-labeled SDB was synthesized and validated for using as an internal standard. This method has been successfully used to measure hydrogen sulfide levels in a broad range of biological matrices, such as blood, plasma, tissues, cells, and enzymes, across different species. Moreover, a novel mode that hydrogen sulfide could loosely and non-covalently bind to human serum protein (HSA) and hemoglobin (HB) was revealed by using the developed method.
Abstract Although left ventricular assist devices ( LVADs ) have been commonly used for patients with cardiogenic shock after acute myocardial infarction ( AMI ), their effects on post‐ AMI prognosis remain to be elucidated. In this study, we aimed to explore the effects of an LVAD on left ventricular ( LV ) remodeling and function at the postinfarction stage in a swine model. AMI was induced by ligation of the circumflex artery or its branches for 120 min, followed by 120 min of reperfusion. In the assist group ( n = 6), LVAD was initiated at 90 min after ischemia and was maintained for support until 120 min after reperfusion, whereas the control group ( n = 6) received no support. LV pressure, volume, wall stress, and stroke work were all decreased by LVAD assistance at the ischemia and reperfusion stages, and blood pressure and cardiac output were maintained. All swine were studied 1 month after the procedure, and those in the assist group showed less increased end‐diastolic volumes (assist vs. control: 57.9 ± 6.6 vs. 79.0 ± 6.7 mL, P = 0.032) and sphericity (assist vs. control: 1.33 ± 0.16 vs. 1.51 ± 0.12, P = 0.01), as well as improved ejection fractions (assist vs. control: 59.0 ± 7.8 vs. 42.3 ± 6.0%, P = 0.002). Furthermore, despite a presence of a similar initial ischemic area, the percent of infarcted myocardium was reduced by 49.9% in the assist group (assist vs. control: 18.1 ± 4.8 vs. 35.3 ± 6.2%, P < 0.001). These results suggested that early assistance with an LVAD in AMI limited LV remodeling, preserved postinfarction systolic function, and improved the prognosis.
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