Protective effects of Terminalia arjuna against Doxorubicin-induced cardiotoxicity

Terminalia arjuna has been marked as a potential cardioprotective agent since vedic period. The present study was aimed to investigate the effects of butanolic fraction of Terminalia arjuna bark (TA-05) on Doxorubicin (Dox)-induced cardiotoxicity. Male wistar rats were used as in vivo model for the study. TA-05 was administered orally to Wistar rats at different doses (0.42 mg/kg, 0.85 mg/kg, 1.7 mg/kg, 3.4 mg/kg and 6.8 mg/kg) for 6 days/week for 4 weeks. Thereafter, all the animals except saline and TA-05-treated controls were administered 20 mg/kg Dox intraperitonially. There was a significant decrease in myocardial superoxide dismutase (38.94%) and reduced glutathione (23.84%) in animals treated with Dox. Concurrently marked increase in serum creatine kinase-MB (CKMB) activity (48.11%) as well as increase in extent of lipid peroxidation (2.55-fold) was reported. Co-treatment of TA-05 and Dox resulted in an increase in the cardiac antioxidant enzymes, decrease in serum CKMB levels and reduction in lipid peroxidation as compared to Dox-treated animals. Electron microscopic studies in Dox-treated animals revealed mitochondrial swelling, Z-band disarray, focal dilatation of smooth endoplasmic reticulum (SER) and lipid inclusions, whereas the concurrent administration of TA-05 led to a lesser degree of Dox-induced histological alterations. These findings suggest that butanolic fraction of Terminalia arjuna bark has protective effects against Dox-induced cardiotoxicity and may have potential as a cardioprotective agent.     

Temporal effect of Guanxin No. 2 on cardiac function, blood viscosity and angiogenesis in rats after long-term occlusion of the left anterior descending coronary artery

AIM: Cardiac infarction is one of the main causes of death in both developing and developed countries over past decades. Currently available approaches for treating patients with this disease are not satisfactory. Traditional Chinese medicines have been increasingly paid attention to. The aim of this study was to characterize the dynamic protective effects of Guanxin No. 2 decoction (GX II) on cardiac dysfunction combined with the blood viscosity and myocardial hypertrophy parameters in myocardial infarction (MI) rats. METHODS: Male Sprague-Dawley rats (180-200 g) were randomly divided into three groups: sham-operated, coronary artery ligation (CAL), and CAL plus GX II (GX II, 10.0 g raw materials/kg/d, bid, p.o.). The experiment was carried out at 4 time points as the 3rd, 7th, 14th, and 28th day after ligation. RESULT: It was found that on the one hand, GX II could significantly improve the heart function, and remarkably decrease infarct size and inhibit ventricular remodeling. On the other hand, GX II showed some unique effects such as angiogenesis which was induced in the left ventricular tissue. This result was consistent with the finding of an augmented vascular endothelial growth factor (VEGF) expression in this area. CONCLUSIONS: The studies demonstrated that GX II exerted extensively beneficial cardioprotective effect on CAL rats, it might stimulate angiogenesis of ischemic region to compensate blood supply to the heart via upregulated VEGF expression.     

α_1—抗胰蛋白酶异质体的测量新方法及其临床意义的探讨

本文对a_1-抗胰蛋白酶异质体的检测方法(小扁豆凝集素亲合交叉免疫电泳法)进行改进。改进后的方法操作流程短、成本低、结果清晰、操作简便、不需预测a_1-抗胰蛋白酶总浓度,适合于临床广泛应用。本文用该法对原发性肝癌、转移性肝癌,其它器官癌肿、肝硬化及正常人血清中的a_1-抗胰蛋白酶异质体进行分析,发现小扁豆凝集素结合型a_1-抗胰蛋白酶百分比(LCA-R-AAT％)原发性肝癌组明显高于其它各组,以LCA-R-AAT(％)>25％为阳性标准,则原发性肝癌诊断的敏感性、特异性、准确性分别为80.6％、86.2％和84.3％,与小扁豆凝集素结合型甲胎蛋白联合检测,可使原发性肝癌诊断的敏感性提高至100％(P<0.05),特异性和准确性分别为82.8％和89.9％(P均>0.05),表明LCA-R-AAT(％)的检测对原发性肝癌的诊断及鉴别诊断有一定的价值。     

Motor Mapping with Functional Magnetic Resonance Imaging: Comparison with Electrical Cortical Stimulation

The aim of the present study was to evaluate motor area mapping using functional magnetic resonance imaging (fMRI) compared with electrical cortical stimulation (ECS). Motor mapping with fMRI and ECS were retrospectively compared in seven patients with refractory epilepsy in which the primary motor (M1) areas were identified by fMRI and ECS mapping between 2012 and 2019. A right finger tapping task was used for fMRI motor mapping. Blood oxygen level-dependent activation was detected in the left precentral gyrus (PreCG)/postcentral gyrus (PostCG) along the “hand knob” of the central sulcus in all seven patients. Bilateral supplementary motor areas (SMAs) were also activated (n = 6), and the cerebellar hemisphere showed activation on the right side (n = 3) and bilateral side (n = 4). Furthermore, the premotor area (PM) and posterior parietal cortex (PPC) were also activated on the left side (n = 1) and bilateral sides (n = 2). The M1 and sensory area (S1) detected by ECS included fMRI-activated PreCG/PostCG areas with broader extent. This study showed that fMRI motor mapping was locationally well correlated to the activation of M1/S1 by ECS, but the spatial extent was not concordant. In addition, the involvement of SMA, PM/PPC, and the cerebellum in simple voluntary movement was also suggested. Combination analysis of fMRI and ECS motor mapping contributes to precise localization of M1/S1.     

Novel Bacteriophage Specific against Staphylococcus epidermidis and with Antibiofilm Activity

Staphylococcus epidermidis has emerged as the most important pathogen in infections related to indwelling medical devices, and although these infections are not life-threatening, their frequency and the fact that they are extremely difficult to treat represent a serious burden on the public health system. Treatment is complicated by specific antibiotic resistance genes and the formation of biofilms. Hence, novel therapeutic strategies are needed to fight these infections. A novel bacteriophage CUB-EPI_14 specific to the bacterial species S. epidermidis was isolated from sewage and characterized genomically and phenotypically. Its genome contains a total of 46,098 bp and 63 predicted genes, among which some have been associated with packaging and lysis-associated proteins, structural proteins, or DNA- and metabolism-associated proteins. No lysogeny-associated proteins or known virulence proteins were identified in the phage genome. CUB-EPI_14 showed stability over a wide range of temperatures (from −20 °C to 50 °C) and pH values (pH 3–pH 12) and a narrow host range against S. epidermidis. Potent antimicrobial and antibiofilm activities were observed when the phage was tested against a highly susceptible bacterial isolate. These encouraging results open the door to new therapeutic opportunities in the fight against resilient biofilm-associated infections caused by S. epidermidis.     

Piperlongumine increases the sensitivity of bladder cancer to cisplatin by mitochondrial ROS

BackgroundThe development of cisplatin resistance often results in cisplatin inefficacy in advanced or recurrent bladder cancer. However, effective treatment strategies for cisplatin resistance have not been well established.MethodsGene expression was measured by qRT‐PCR and Western blotting. CCK‐8 assay was performed to detect cell survival. The number of apoptotic cells was determined using the Annexin V‐PI double‐staining assay. The level of reactive oxygen species (ROS) was measured using 2’,7''‐dichlorodihydrofluorescein diacetate fluorescent dye, and the ATP level was detected using an ATP measurement kit.ResultsThe expression of receptor‐interacting protein kinase 1 (RIPK1), a key regulator of necroptosis, gradually decreased during cisplatin resistance. We first used piperlongumine (PL) in combination with cisplatin to act on cisplatin‐resistant BC cells and found that PL‐induced activation of RIPK1 increased the sensitivity of T24 resistant cells to cisplatin treatment. Furthermore, we revealed that PL killed T24 cisplatin‐resistant cells by triggering necroptosis, because cell death could be rescued by the mixed lineage kinase domain‐like (MLKL) protein inhibitor necrotic sulfonamide or MLKL siRNA, but could not be suppressed by the apoptosis inhibitor z‐VAD. We further explored the specific mechanism and found that PL activated RIPK1 to induce necroptosis in cisplatin‐resistant cells by stimulating mitochondrial fission to produce excessive ROS.ConclusionsOur results demonstrated the role of RIPK1 in cisplatin‐resistant cells and the sensitization effect of the natural drug PL on bladder cancer. These may provide a new treatment strategy for overcoming cisplatin resistance in bladder cancer.     

Asymptomatic Malaria in Households and Neighbors of Laboratory Confirmed Cases in Raya Kobo District,Northeast Ethiopia

BackgroundMalaria is the leading vector-borne parasitic disease that is causing high morbidity and mortality worldwide. So far huge efforts to control and eliminate malaria are hindered by the occurrence of asymptomatic carriers that are a potential source of infection. Yet, there is a scarcity of data nationally and in the current study area as well. Therefore, this study was aimed to assess the prevalence of asymptomatic malaria in Northeast Ethiopia.MethodsA community-based cross-sectional study was conducted in 2019 involving a total of 270 study participants recruited via purposive non-probability sampling technique. A structured questionnaire was used to collect data on sociodemographic characteristics, individual and household factors related to asymptomatic malaria. Data were entered in Epi Data 3.1 version and analyzed by using SPSS version 20, and p< 0.05 was considered statistically significant.ResultsThe overall prevalence of asymptomatic malaria was 7.0%, with 3.0%, 5.2%, and 12.0%, respectively by Rapid diagnostic tests (RDT), Microscopy and Polymerase chain reaction (PCR). The majority of infections (73.7%) were identified from index households. Previous malaria history (AOR: 4.030, 95% CI: 1.021–15.903), living with index cases (AOR: 3.880, 95% CI: 1.275–11.806) and family size > 6 members (AOR: 4.820, 95% CI: 1.260–18.437) were significant predictors of asymptomatic malaria.ConclusionReactive case detection had identified considerably higher asymptomatic malaria cases in the community. Therefore, active case investigation should be established in the community by tracking the symptomatic cases at the health facilities.     

Glycine induces enhancement of bactericidal activity of neutrophils

Severe bacterial infections are frequently accompanied by depressed neutrophil functions. Thus, agents that increase the microbicidal activity of neutrophils could add to a direct antimicrobial therapy. Lysophosphatidylcholine augments neutrophil bactericidal activity via the glycine (Gly)/glycine receptor (GlyR) α2/TRPM2/p38 mitogen-activated protein kinase (MAPK) pathway. However, the direct effect of glycine on neutrophil bactericidal activity was not reported. In this study, the effect of glycine on neutrophil bactericidal activity was examined. Glycine augmented bactericidal activity of human neutrophils (EC₅₀ = 238 μM) in a strychnine (a GlyR antagonist)-sensitive manner. Glycine augmented bacterial clearance in mice, which was also blocked by strychnine (0.4 mg/kg, s.c.). Glycine enhanced NADPH oxidase-mediated reactive oxygen species (ROS) production and TRPM2-mediated [Ca²⁺]_i increase in neutrophils that had taken up E. coli. Glycine augmented Lucifer yellow uptake (fluid-phase pinocytosis) and azurophil granule-phagosome fusion in neutrophils that had taken up E. coli in an SB203580 (a p38 MAPK inhibitor)-sensitive manner. These findings indicate that glycine augments neutrophil microbicidal activity by enhancing azurophil granule-phagosome fusion via the GlyRα2/ROS/calcium/p38 MAPK pathway. We suggest that glycine could be a useful agent for increasing neutrophil bacterial clearance.     

New Insight into the Gas Phase Reaction Dynamics in Pulsed Laser Deposition of Multi-Elemental Oxides

The gas-phase reaction dynamics and kinetics in a laser induced plasma are very much dependent on the interactions of the evaporated target material and the background gas. For metal (M) and metal–oxygen (MO) species ablated in an Ar and O₂ background, the expansion dynamics in O₂ are similar to the expansion dynamics in Ar for M⁺ ions with an MO⁺ dissociation energy smaller than O₂. This is different for metal ions with an MO⁺ dissociation energy larger than for O₂. This study shows that the plume expansion in O₂ differentiates itself from the expansion in Ar due to the formation of MO⁺ species. It also shows that at a high oxygen background pressure, the preferred kinetic energy range to form MO species as a result of chemical reactions in an expanding plasma, is up to 5 eV.