旋转磁场治疗印^60CO辐射造血损伤小鼠生存分析的实验研究

目的：初步探讨旋转恒定磁场治疗急性骨髓型放射病的效果。方法：BALB／C小鼠按体重随机分为磁疗组和对照组，每组再各分为4组．分别接受0Gy、6．0Gy、8．0Gy、10．0Gy ^60COγ射线全身辐射，照后，对照组不作任何处理，磁疗组接受磁场处理30d，每天2次，每次1．5h，旋转磁场强度为0．6T，比较两组小鼠30d的存活率和存活期。结果：单纯磁场处理对正常小鼠生存状态及存活率无明显影响；10．0Gy组和8．0Gy组小鼠生存率磁疗组与对照组之间比较均无统计学差异（P〉0．05）；6．0Gy组生存率磁疗组和对照组之间比较有统计学差异（P〈0．05），其磁疗组30d平均存活率为71．43％，平均存活期为（24．93±8．43）d，对照组30d平均存活率21．4l％．平均存活期为（17．07±7．70）d。结论：旋转恒定磁场不能提高10．0Gy及8．0Gy剂量所致极重度急性骨髓型放射病小鼠的生存率，但对6．0Gy所致重度急性骨髓型放射病有明显的保护作用，从而为旋转恒定磁场应用于临床治疗重度急性骨髓型放射损伤提供了实验依据。     

SOCS2 Balances Metabolic and Restorative Requirements during Liver Regeneration

After significant injury, the liver must maintain homeostasis during the regenerative process. We hypothesized the existence of mechanisms to limit hepatocyte proliferation after injury to maintain metabolic and synthetic function. A screen for candidates revealed suppressor of cytokine signaling 2 (SOCS2), an inhibitor of growth hormone (GH) signaling, was strongly induced after partial hepatectomy. Using genetic deletion and administration of various factors we investigated the role of SOCS2 during liver regeneration. SOCS2 preserves liver function by restraining the first round of hepatocyte proliferation after partial hepatectomy by preventing increases in growth hormone receptor (GHR) via ubiquitination, suppressing GH pathway activity. At later times, SOCS2 enhances hepatocyte proliferation by modulating a decrease in serum insulin-like growth factor 1 (IGF-1) that allows GH release from the pituitary. SOCS2, therefore, plays a dual role in modulating the rate of hepatocyte proliferation. In particular, this is the first demonstration of an endogenous mechanism to limit hepatocyte proliferation after injury.     

铁过载促进小鼠肝组织发生蛋白质酪氨酸硝化

蛋白质酪氨酸硝化是一种蛋白质翻译后的修饰，其存在会影响酶的催化活性，细胞信号转导和细胞骨架结构．在铁过载情况下，存在引起蛋白质酪氨酸硝化的有利环境，但目前尚无实验证实．本文运用腹腔注射右旋糖苷铁造成小鼠铁过载模型，通过免疫印迹法发现，在铁过载情况下，肝中诱导型一氧化氮合酶表达显著高于正常对照小鼠；铁过载小鼠肝中总体蛋白质硝化程度高于正常小鼠；铁过载引起的蛋白质酪氨酸硝化有一定的选择性，在铁过载小鼠肝中发现一些新的被硝化蛋白质条带（约 57 kD、 35 kD）．上述结果证实，铁过载会促进肝蛋白质酪氨酸硝化．     

ERK/MAPK and PI3K/AKT signal channels simultaneously activated in nerve cell and axon after facial nerve injury

BackgroundThe in-vitro study indicated that ERK/MAPK and PI3K/AKT signal channels may play an important role in reparative regeneration process after peripheral nerve injury. But, relevant in-vivo study was infrequent. In particular, there has been no report on simultaneous activation of ERK/MAPK and PI3K/AKT signal channels in facial nerve cell and axon after facial nerve injury.ResultsThe expression of P-ERK enhanced in nerve cells at the injury side on the 1 d after the rat facial nerve was cut and kept on a higher level until 14 d, but decreased on 28 d. The expression of P-AKT enhanced in nerve cells at the injury side on 1 d after injury, and kept on a higher level until 28 d. The expression of P-ERK enhanced at the near and far sections of the injured axon on 1 d, then increased gradually and reached the maximum on 7 d, but decreased on 14 d, until down to the level before the injury on 28 d. The expression of P-AKT obviously enhanced in the injured axon on 1 d, especially in the axon of the rear section, but decreased in the axon of the rear section on 7 d, while the expression of axon in the far section increased to the maximum and kept on till 14 d. On 28 d, the expression of P-AKT decreased in both rear and far sections of the axon.ConclusionThe facial nerve simultaneously activated ERK/MAPK and PI3K/AKT signal channels in facial nerve cells and axons after the cut injury, but the expression levels of P-ERK and P-AKT varied as the function of the time. In particular, they were quite different in axon of the far section. It has been speculated that two signal channels might have different functions after nerve injury. However, their specific regulating effects should still be testified by further studies in regenerative process of peripheral nerve injury.     

Chronic ethanol ingestion induces oxidative kidney injury through taurine-inhibitable inflammation

Chronic ethanol ingestion mildly damages liver through oxidative stress and lipid oxidation, which is ameliorated by dietary supplementation with the anti-inflammatory β-amino acid taurine. Kidney, like liver, expresses cytochrome P450 2E1 that catabolizes ethanol with free radical formation, and so also may be damaged by ethanol catabolism. Sudden loss of kidney function, and not liver disease itself, foreshadows mortality in patients with alcoholic hepatitis [J. Altamirano, Clin. Gastroenterol. Hepatol. 2012, 10:65]. We found that ethanol ingestion in the Lieber-deCarli rat model increased kidney lipid oxidation, 4-hydroxynonenal protein adduction, and oxidatively truncated phospholipids that attract and activate leukocytes. Chronic ethanol ingestion increased myeloperoxidase-expressing cells in kidney and induced an inflammatory cell infiltrate. Apoptotic terminal deoxynucleotidyl transferase nick-end labeling-positive cells and active caspase-3 increased in kidney after ethanol ingestion, with reduced filtration with increased circulating blood urea nitrogen (BUN) and creatinine. These events were accompanied by release of albumin, myeloperoxidase, and the acute kidney injury biomarkers kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin, and cystatin c into urine. Taurine sequesters HOCl from myeloperoxidase of activated leukocytes, and taurine supplementation reduced renal lipid oxidation, reduced leukocyte infiltration, and reduced the increase in myeloperoxidase-positive cells during ethanol feeding. Taurine supplementation also normalized circulating BUN and creatinine levels and suppressed enhanced myeloperoxidase, albumin, KIM-1, and cystatin c in urine. Thus, chronic ethanol ingestion oxidatively damages kidney lipids and proteins, damages renal function, and induces acute kidney injury through an inflammatory cell infiltrate. The anti-inflammatory nutraceutical taurine effectively interrupts this ethanol-induced inflammatory cycle in kidney.     

Rutin decreases lipopolysaccharide-induced acute lung injury via inhibition of oxidative stress and the MAPK–NF-κB pathway

Acute lung injury (ALI) is a serious disease with unacceptably high mortality and morbidity rates. Up to now, no effective therapeutic strategy for ALI has been established. Rutin, quercetin-3-rhamnosyl glucoside, expresses a wide range of biological activities and pharmacological effects, such as anti-inflammatory, antihypertensive, anticarcinogenic, vasoprotective, and cardioprotective activities. Pretreatment with rutin inhibited not only histopathological changes in lung tissues but also infiltration of polymorphonuclear granulocytes into bronchoalveolar lavage fluid in lipopolysaccharide (LPS)-induced ALI. In addition, LPS-induced inflammatory responses, including increased secretion of proinflammatory cytokines and lipid peroxidation, were inhibited by rutin in a concentration-dependent manner. Furthermore, rutin suppressed phosphorylation of NF-κB and MAPK and degradation of IκB, an NF-κB inhibitor. Decreased activities of antioxidative enzymes such as superoxide dismutase, catalase, glutathione peroxidase, and heme oxygenase-1 caused by LPS were reversed by rutin. At the same time, we found that ALI amelioration by chelation of extracellular metal ions with rutin is more efficacious than with deferoxamine. These results indicate that the protective mechanism of rutin is through inhibition of MAPK–NF-κB activation and upregulation of antioxidative enzymes.     

Electromyographic analysis of rotator cuff muscles in patients with rotator cuff tendinopathy: A systematic review

The shoulder is inherently an unstable joint which heavily relies on the neuromuscular activation of the rotator cuff (RC) complex for stability during movement. Currently, there is no consensus regarding how the activity of RC muscles is affected among individuals with a RC tendinopathy (RCTe). This study reviewed the evidence of studies comparing the electromyographic (EMG) activity of any RC muscle of shoulders with a symptomatic RCTe to asymptomatic shoulders. Eight databases were searched. Data from 343 participants (201 symptomatic and 209 asymptomatic shoulders) were analyzed from 10 out of 402 included studies. Strong evidence for the infraspinatus and supraspinatus during isometric contractions and limited evidence for the supraspinatus and infraspinatus during isokinetic contractions suggest that the muscular activity is not altered among individuals with a RCTe during these types of contraction. Very limited evidence indicates reduced muscle activity for the infraspinatus and subscapularis in the presence of a RCTe during isotonic contractions, and no alterations for the supraspinatus or teres minor were identified. Lastly, conflicting to moderate evidence suggests alterations in RC muscle activity during unrestrained movements and swimming. These findings indicate that EMG deficits associated with a RCTe can best be appreciated during unrestrained movements.     

Neutral sphingomyelinase inhibition alleviates apoptosis,but not ER stress,in liver ischemia–reperfusion injury

Previous studies have revealed the activation of neutral sphingomyelinase (N-SMase)/ceramide pathway in hepatic tissue following warm liver ischemia reperfusion (IR) injury. Excessive ceramide accumulation is known to potentiate apoptotic stimuli and a link between apoptosis and endoplasmic reticulum (ER) stress has been established in hepatic IR injury. Thus, this study determined the role of selective N-SMase inhibition on ER stress and apoptotic markers in a rat model of liver IR injury. Selective N-SMase inhibitor was administered via intraperitoneal injections. Liver IR injury was created by clamping blood vessels supplying the median and left lateral hepatic lobes for 60?min, followed by 60?min reperfusion. Levels of sphingmyelin and ceramide in liver tissue were determined by an optimized multiple reactions monitoring (MRM) method using ultrafast-liquid chromatography (UFLC) coupled with tandem mass spectrometry (MS/MS). Spingomyelin levels were significantly increased in all IR groups compared with controls. Treatment with a specific N-SMase inhibitor significantly decreased all measured ceramides in IR injury. A significant increase was observed in ER stress markers C/EBP-homologous protein (CHOP) and 78?kDa glucose-regulated protein (GRP78) in IR injury, which was not significantly altered by N-SMase inhibition. Inhibition of N-SMase caused a significant reduction in phospho-NF-kB levels, hepatic TUNEL staining, cytosolic cytochrome c, and caspase-3, -8, and -9 activities which were significantly increased in IR injury. Data herein confirm the role of ceramide in increased apoptotic cell death and highlight the protective effect of N-SMase inhibition in down-regulation of apoptotic stimuli responses occurring in hepatic IR injury.     

Involvement of Nox2 and Nox4 NADPH oxidases in early brain injury after subarachnoid hemorrhage

Oxidative stress is responsible for a poor prognosis of subarachnoid hemorrhage (SAH) patients. Nox2 has been shown to participate in SAH-induced early brain injury (EBI). Nox4 is another major subtype of Nox family widely expressed in central nervous system (CNS). Here, we investigated the role of Nox4 and whether there was a synergistic effect of Nox2 and Nox4 in SAH-induced EBI. Clinical brain biopsies of four patients with traumatic brain injury (TBI) and perihematomal brain tissue from six subjects with SAH were examined. Gp91ds-tat (a specific inhibitor of Nox2), GKT137831 (a specific inhibitor of Nox4), and apocynin (a non-specific Nox inhibitor) were used to test the role of Nox2 and Nox4. The protein levels of Nox2 and Nox4 were elevated in rat neurons and astrocytes at 12?h after SAH, and in cultured brain microvascular endothelial cells at 24?h after exposure to OxyHb. Similarly, there were higher Nox2 and Nox4 protein levels in perihematomal neurons and astrocytes in SAH patients than that in brain tissue from subjects with TBI. In SAH rat model, gp91ds-tat and GKT137831 could reduce SAH-induced neuronal death and degeneration, whereas apocynin did not induce a more intense neuroprotection. Consistently, in in vitro SAH model, siRNA-mediated silencing of Nox2 and Nox4 suppressed the OxyHb-induced neuronal apoptosis, whereas Nox2 and Nox4 co-knockdown also did not show a remarkable overlay effect. In conclusion, Nox4 should contribute to the pathological processes in SAH-induced EBI, and there was not an overlay effect of Nox2 inhibition and Nox4 inhibition on preventing SAH-induced EBI.