Background: Doxorubicin (DOX) is an effective antineoplastic drug; however, clinical use of DOX is limited by its dose-dependent cardiotoxicity. It is well known that reactive oxygen species (ROS) play a vital role in the pathological process of DOX-induced cardiotoxicity. For this study, we evaluated the protective effects of guggulsterone (GS), a steroid obtained from myrrh, to determine its preliminary mechanisms in defending against DOX-induced cytotoxicity in H9C2 cells.Methods: In this study, we used a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, lactate dehydrogenase (LDH) release measurements, and Hoechst 33258 staining to evaluate the protective effect of GS against DOX-induced cytotoxicity in H9C2 cells. In addition, we observed the immunofluorescence of intracellular ROS and measured lipid peroxidation, caspase-3 activity, and apoptosis-related proteins by using Western blotting.Results: The MTT assay and LDH release showed that treatment using GS (1–30 μM) did not cause cytotoxicity. Furthermore, GS inhibited DOX (1 μM)-induced cytotoxicity in a concentration-dependent manner. Hoechst 33258 staining showed that GS significantly reduced DOX-induced apoptosis and cell death. Using GS at a dose of 10–30 μM significantly reduced intracellular ROS and the formation of MDA in the supernatant of DOX-treated H9C2 cells and suppressed caspase-3 activity to reference levels. In immunoblot analysis, pretreatment using GS significantly reversed DOX-induced decrease of PARP, caspase-3 and bcl-2, and increase of bax, cytochrome C release, cleaved-PARP and cleaved-caspase-3. In addition, the properties of DOX-induced cancer cell (DLD-1 cells) death did not interfere when combined GS and DOX.Conclusion: These data provide considerable evidence that GS could serve as a novel cardioprotective agent against DOX-induced cardiotoxicity.

Background. The optimal dose and concentration of analgesic efficacy of ropivacaine (RPV) and bupivacaine (BPV) for postoperative pain relief in paediatric abdominal surgery patients is still unclear. Therefore, this meta-analysis compared the efficacy of these analgesics, their administered modes (ultrasound-guided RSB versus LAI) for postoperative pain relief, and side effects. Methods. Three databases, PubMed, Embase, and Cochrane Database of Systematic Reviews, were exhaustively searched with predefined keywords. Eight randomized clinical trials and retrospective studies were selected. Analgesic effect, postoperative pain score, level of side effect, applied dose, and concentration of drug were analysed. Results. Drug dose ranged from 0.5–2.5 mL/kg of 0.2 to 0.5% concentrations. Male participant for RSB and LAI treatment groups varied from 40–62% and 25–83%, respectively. Mean age of RSB and LAI groups ranged from 3.8–11.65 years and 4.3–11.27 years, respectively. Our meta-analysis revealed that RSB could reduce total opioid use postoperatively (WMD = −0.02, 95% CI: −0.02, −0.02), with I² value of 15%. We found that the RPV (0.25%, 2.5 ml/kg) was optimal in suppressing the pain. Its lower concentration (0.2%) was ineffective, whereas higher one (0.375%) seems to increase risk of systemic toxicity. Similarly, BPV (0.25%, 2.5 mg/kg) efficaciously reduced the pain score, while its lower concentration was ineffective. The combined postoperative pain score in the RPV-treated group was found to be significantly reduced ( ) with I² value of 85% indicating high heterogeneity. Conclusion. Both RPV and BPV were significantly effective in reducing postoperative pain score. It appears that RSB could be a preferred choice to deliver analgesia, due to reduced opiate dose requirement and improved clinical safety without significant postoperative adverse events.

Background: In the past several decades,Polygonum viviparumL. (PV) was reported to have antibacterial, antiulcer, antioxidant, antitumor, anti-inflammatory, and antiarthritic properties. The anti-inflammatory pathway was recently elucidated through cytosolic nuclear factor E2-related factor 2 (Nrf2) activation and heme oxygenase (HO)-1 protein expression. PV is a perennial herb and widely distributed in high-elevation mountain regions, such as the Tibetan Plateau. In Tibetan traditional medicine, PV is usually used to boost the blood circulation to dissipate blood stasis. Therefore, this study focused on how PV improves the vascular circulation and acts on vascular tissues.Methods: In this study, we isolated aortas from Sprague-Dawley rats (male, weight about 250 ~ 350 g), and detected the effects of PV on phenylephrine (PE)-induced contraction and cyclic guanosine 3′,5′-monophosphate (cGMP) formation using aortic rings. In addition, human umbilical vein endothelial cells (HUVECs) were used to exam nitric oxygen (NO) synthase (NOS) activity by directly measuring NO production in the culture medium. Endothelial (e) NOS phosphorylation, and cytosolic Nrf2 and HO-1 expressions were measured using a Western blot analysis.Results: PV dose-dependently relaxed PE-induced contractions in endothelial-intact but not -denuded aorta. The concentration to produce 50% relaxation was 22.04 ± 1.77 μg/ml. PV-induced vasorelaxation was markedly blocked by pretreatment withN^G-nitro-_L-arginine methyl ester (L-NAME), an NOS inhibitor, methylene blue (MB), a guanylyl cyclase inhibitor, and hemoglobin, an NO scavenger. PV increased cGMP formation; however, this effect was also suppressed by co-pretreatment withl-NAME, MB, hemoglobin, and Ca²⁺-free medium. In HUVECs, PV increased NO formation, which was greatly attenuated by NOS inhibitors (L-NAME and L-NMMA) and by removing extracellular Ca²⁺and chelating intracellular Ca²⁺with BAPTA-AM. In addition, PV promoted eNOS phosphorylation, Nrf2 degradation, and HO-1 protein expression according to a Western blot analysis.Conclusions: The results suggest that PV possesses vasorelaxing action in an endothelium-dependent manner and works through activating Ca²⁺/calmodulin- dependent NO synthesis; when NO is released and then transferred to smooth muscle cells, NO activates guanylyl cyclase and increases cGMP formation, ultimately resulting in vasorelaxation. Thus, PV can be considered for application as a potential therapeutic approach for vascular-associated disorders.

Both vasculature and myocardium in the heart are excessively damaged following myocardial infarction (MI), hence therapeutic strategies for treating MI hearts should concurrently aim for true cardiac repair by introducing new cardiomyocytes to replace lost or injured ones. Of them, mesenchymal stem cells (MSCs) have long been considered a promising candidate for cell-based therapy due to their unspecialized, proliferative differentiation potential to specific cell lineage and, most importantly, their capacity of secreting beneficial paracrine factors which further promote neovascularization, angiogenesis, and cell survival. As a consequence, the differentiated MSCs could multiply and replace the damaged tissues to and turn into tissue- or organ-specific cells with specialized functions. These cells are also known to release potent anti-fibrotic factors including matrix metalloproteinases, which inhibit the proliferation of cardiac fibroblasts, thereby attenuating fibrosis. To achieve the highest possible therapeutic efficacy of stem cells, the other interventions, including hydrogels, electrical stimulations, or platelet-derived biomaterials, have been supplemented, which have resulted in a narrow to broad range of outcomes. Therefore, this article comprehensively analyzed the progress made in stem cells and combinatorial therapies to rescue infarcted myocardium.

Carbon monoxide (CO) poisoning is a public health issue in numerous countries. Oxygen supplementation is the standard and initial management for acute CO poisoning. Normobaric oxygen (NBO) and hyperbaric oxygen (HBO) therapies for CO poisoning have been discussed for several decades. NBO, one-session HBO, two-session HBO, and three-session HBO have not been clearly compared, although there are some syntheses. Therefore, this study aimed to provide an overview of various HBO therapies for CO poisoning. We searched online databases for randomized controlled trials (RCTs) on this topic, and two authors individually extracted data on characteristics, mortality, headache recovery, general fatigue, memory impairment, and difficulty concentrating. Outcomes were pooled using network meta-analysis. We included eight RCTs (n = 1785) that met our eligibility criteria. Pooled estimates showed that HBO had no better outcomes than NBO. Moreover, two-session HBO seemed to have a higher general fatigue rate than NBO, and compared with one-session HBO therapy, it had a higher fatigue rate (risk ratio (RR): 1.29, 95% confidence interval (CI): 1.03–1.62), memory impairment rate (RR = 1.80, 95% CI: 1.01–3.19), and concentration impairment rate (RR = 1.85, 95% CI: 1.19–2.89). HBO may be ineffective for patients with CO poisoning. Therefore, clinicians should consider the available treatment options carefully before recommending HBO to patients.

Gastroenteritis promotes the development of systemic inflammation and a hypercoagulable state. There are limited data regarding the association between gastroenteritis and acute myocardial infarction (AMI). We aimed to evaluate the risk of AMI after an episode of gastroenteritis. In this nested case-control study, we selected patients who were hospitalized for AMI (N = 103,584) as a case group during 2010–2017 and performed propensity score matching (case-control ratio 1:1) to select eligible controls from insurance research data in Taiwan. We applied multivariable logistic regressions to calculate adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for the risk of AMI associated with recent gastroenteritis within 14 days before AMI. We also compared the outcomes after AMI in patients with or without gastroenteritis. A total of 1381 patients (1.3%) with AMI had a prior episode of gastroenteritis compared to 829 (0.8%) among the controls. Gastroenteritis was significantly associated with a subsequent risk of AMI (adjusted OR: 1.68, 95% CI: 1.54–1.83), which was augmented in hospitalizations for gastroenteritis (adjusted OR: 2.50, 95% CI: 1.20–5.21). The outcomes after AMI were worse in patients with gastroenteritis than in those without gastroenteritis, including increased 30-day in-hospital mortality (adjusted OR: 1.28, 95% CI: 1.08–1.52), medical expenditure, and length of hospital stay. Gastroenteritis may act as a trigger for AMI and correlates with worse post-AMI outcomes. Strategies of aggressive hydration and/or increased antithrombotic therapies for this susceptible population should be further developed.