Impact loading in female runners with single and multiple bone stress injuries during fresh and exerted conditions

Background:Bone stress injuries(BSIs)are common in female runners,and recurrent BSI rates are high.Previous work suggests an association between higher impact loading during running and tibial BSI.However,it is unknown whether impact loading and fatigue-related loading changes discriminate women with a history of multiple BSIs.This study compared impact variables at the beginning of a treadmill run to exertion andthe changes in those variables with exertion among female runners with no history of BSI as well as among those with a history of single or multiple BSIs.Methods:We enrolled 45 female runners(aged 18-40 years)for this cross-sectional study:having no history of diagnosed lower extremity BSI(N-BSI,n=14);a history of 1 lower extremity BSI(1-BSI,n=16);and diagnosed by imaging,or a history of multiple(>3)lower extremity BSIs(M-BSI,n=15).Participants completed a 5-km race speed run on an instrumented treadmill while wearing an Inertial Measurement Unit.The vertical average loading rate(VALR),vertical instantaneous loading rate(VILR),vertical stiffness during impact via instrumented treadmill,and tibial shock determined as the peak po sitive tibial acceleration via Inertial Measurement Unit were measured at the beginning and the end of the run.Results:There were no differences between groups in VALR,VILR,vertical stiffness,or tibial shock in a fresh or exerted condition.However,compared to N-BSI,women with M-BSI had greater increase with exertion in VALR(-1.8%vs.6.1%,p=0.01)and VILR(1.5%vs.4.8%,p=0.03).Similarly,compared to N-BSI,vertical stiffness increased more with exertion among women with M-BSI(-0.9%vs.7.3%,p=0.006)and 1-BSI(-0.9%vs.1.8%,p=0.05).Finally,compared to N-BSI,the increase in tibial shock from fresh to exerted condition was greater among women with M-BSI(0.9%vs.5.5%,p=0.03)and 1-BSI(0.9%vs.11.2%,p=0.02).Conclusion:Women with 1-BSI or M-BSIs experience greater exertion-related increases in impact loading than women with N-BSI.These observations imply that exertion-related changes in gait biomechanics may contribute to risk of BSI.

Biomechanics associated with tibial stress fracture in runners:A systematic review and meta-analysis

Background:Tibial stress fracture(TSF)is an overuse running injury with a long recovery period.While many running studies refer to biomechanical risk factors for TSF,only a few have compared biomechanics in runners with TSF to controls.The aim of this systematic review and meta-analysis was to evaluate biomechanics in runners with TSF compared to controls.Methods:Electronic databases PubMed,Web of Science,SPORTDiscus,Scopus,Cochrane,and CINAHL were searched.Risk of bias was assessed and meta-analysis conducted for variables reported in 3 or more studies.Results:The search retrieved 359 unique records,but only the 14 that compared runners with TSF to controls were included in the review.Most studies were retrospective,2 were prospective,and most had a small sample size(5-30 per group).Many variables were not significantly different between groups.Meta-analysis of peak impact,active,and braking ground reaction forces found no significant differences between groups.Individual studies found larger tibial peak anterior tensile stress,peak posterior compressive stress,peak axial acceleration,peak rearfoot eversion,and hip adduction in the TSF group.Conclusion:Meta-analysis indicated that discrete ground reaction force variables were not statistically significantly different in runners with TSF compared to controls.In individual included studies,many biomechanical variables were not statistically significantly different between groups.However,many were reported by only a single study,and sample sizes were small.We encourage additional studies with larger sample sizes of runners with TSF and controls and adequate statistical power to confirm or refute these findings.

Lycium barbarum polysaccharides protects retinal ganglion cells against oxidative stress injury

The accumulation of excessive reactive oxygen species can exacerbate any injury of retinal tissue because free radicals can trigger lipid peroxidation,protein damage and DNA fragmentation.Increased oxidative stress is associated with the common pathological process of many eye diseases,such as glaucoma,diabetic retinopathy and ischemic optic neuropathy.Many studies have demonstrated that Lycium barbarum polysaccharides(LBP)protects against oxidative injury in numerous cells and tissues.For the model of hypoxia we used cultured retinal ganglion cells and induced hypoxia by incubating with 200μM cobalt chloride(CoCl2)for 24 hours.To investigate the protective effect of LBP and its mechanism of action against oxidative stress injury,the retinal tissue was pretreated with 0.5 mg/mL LBP for 24 hours.The results of flow cytometric analysis showed LBP could effectively reduce the CoCl2-induced retinal ganglion cell apoptosis,inhibited the generation of reactive oxygen species and the reduction of mitochondrial membrane potential.These findings suggested that LBP could protect retinal ganglion cells from CoCl2-induced apoptosis by reducing mitochondrial membrane potential and reactive oxygen species.

Attenuation of endoplasmic reticulum stress as a treatment strategy against ischemia/reperfusion injury

Brain ischemic stroke is the leading cause of long-lasting injury,disability,and death in adults.Although the brain represents only about 2%of the total body mass,it consumes almost 20%of the body＇s oxygen.As a result,brain cells are extremely sensitive to hypoxia.Once cerebral ischemia occurs.

Incidence investigation and analysis of hepatic stress injury after trauma

Objective To investigate the etiology and pathogenesis of hepatic stress injury after trauma.Methods 4 677 patients with severe trauma in 153th Hospital of PLA from Jan.2004 to Jul.2005 were enrolled in this study to investigate the incidence of hepatic stress injury,and furthermore,in combination with medical information,the possible pathogenesis was analyzed.Results The main manifestation of hepatic stress injury was the elevated ALT or AST levels(387 cases,8.3%).The incidence of hepatic stress injury after hand injury,burn injury,head injury,bone injury,abdominal injury,and thoracic injury were 16.6%,6.9%,5.6%,5.0%,3.8% and 2.0%,respectively,and among which,the incidence of hepatic stress injury after hand injury was statistically highest(P<0.01).Conclusion The total incidence of hepatic stress injury after trauma was 8.3%.Intestinal endotoxemia might be one of the beginning components of hepatic stress injury after trauma.

BH3-only protein Bim is involved in myocardial injury induced by co-stress of ischemia and cold stress in rats

Objectives To investigate the effect of co-exposure of myocardial ischemia and cold stress on myocardial injury in rats and the relative mechanism.Methods Myocardial ischemia model was established by ligation of left coronary artery.SD rats were randomly allocated to 4 groups; sham+normal temperature(S group),sham+cold stress(SC group),myocardial ischemia+ normal temperature(Ⅰgroup), myocardial ischemia+cold stress(IC group).On the condition of 26℃,SC and IC groups were keeped in a 4℃artificial chamber for 8h(8;00-16:00) for 4 consecu- tive days.Car diac function was assessed by echocardiography;pathological change was analyzed by HE staining;myocardial infarct size was determined by TTC staining;Bim,Caspase-3 expression in myocardium was determined by western blotting.Results It was demonstrated that co-exposure of myocardial ischemia and cold stress could significantly make the cardiac muscle in abnormal shape,increase the infarct size and the expression of Bim and Caspase-3.Conclusions Co-exposure of myocardial ischemia and cold stress may aggravate the cardiac injury,pro- apoptosis protein Bim is involved.

Protective effect of extracorporeal membrane pulmonary oxygenation combined with cardiopulmonary resuscitation on post-resuscitation lung injury

BACKGROUND: Cardiac arrest(CA) is a critical condition that is a concern to healthcare workers. Comparative studies on extracorporeal cardiopulmonary resuscitation(ECPR) and conventional cardiopulmonary resuscitation(CCPR) technologies have shown that ECPR is superior to CCPR. However, there is a lack of studies that compare the protective effects of these two resuscitative methods on organs. Therefore, we aim to perform experiments in swine models of ventricular fibrillation-induced CA to study whether the early application of ECPR has advantages over CCPR in the lung injury and to explore the protective mechanism of ECPR on the post-resuscitation pulmonary injury.METHODS: Sixteen male swine were randomized to CCPR(CCPR;n=8;CCPR alone) and ECPR(ECPR;n=8;extracorporeal membrane oxygenation with CCPR) groups, with the restoration of spontaneous circulation at 6 hours as an endpoint. RESULTS: For the two groups, the survival rates between the two groups were not statistically significant(P>0.05), the blood and lung biomarkers were statistically significant(P<0.05), and the extravascular lung water and pulmonary vascular permeability index were statistically significant(P<0.01). Compared with the ECPR group, electron microscopy revealed mostly vacuolated intracellular alveolar type II lamellar bodies and a fuzzy lamellar structure with widening and blurring of the blood-gas barrier in the CCPR group.CONCLUSIONS: ECPR may have pulmonary protective effects, possibly related to the regulation of alveolar surface-active proteins and mitigated oxidative stress response postresuscitation.

Injury of cortical neurons is caused by the advanced glycation end products-mediated pathway

Advanced glycation end products lead to cell apoptosis, and cause cell death by increasing endoplasmic reticulum stress. Advanced glycation end products alone may also directly cause damage to tissues and cells, but the precise mechanism remains unknown. This study used primary cultures of rat cerebral cortex neurons, and treated cells with different concentrations of glycation end products （50, 100, 200, 400 mg/L）, and with an antibody for the receptor of advanced glycation end products before and after treatment with advanced glycation end products. The results showed that with increasing concentrations of glycation end products, free radical content increased in neurons, and the number of apoptotic cells increased in a dose-dependent manner. Before and after treatment of advanced glycation end products, the addition of the antibody against advanced glycation end-products markedly reduced hydroxyl free radicals, malondialdehyde levels, and inhibited cell apoptosis. This result indicated that the antibody for receptor of advanced glycation end-products in neurons from the rat cerebral cortex can reduce glycation end product-induced oxidative stress damage by suppressing glycation end product receptors. Overall, our study confirms that the advanced glycation end products-advanced glycation end products receptor pathway may be the main signaling pathway leading to neuronal damage.

Safety and feasibility of irreversible electroporation for the pancreatic head in a porcine model

BACKGROUND Irreversible electroporation(IRE)is a local non-thermal ablative technique which has been suggested as a potential cancer therapy.However,the specific anatomic characteristics of the pancreatic head make it challenging to perform any local ablation in this region.Therefore,the safety and feasibility of IRE in the pancreatic head region should be further explored.AIM To evaluate the safety of IRE in pancreatic head region including its effects on pancreatic ducts,vessels,and adjacent gastrointestinal organs.METHODS Eight landrace miniature pigs underwent IRE of pancreatic head tissue successfully,with a total of 16 lesions created.Laboratory testing including white blood cell(WBC)count and serum amylase before IRE with follow-up laboratory analysis and pathological examination at 1,7,14,and 28 d postablation were performed.RESULTS All pigs tolerated the ablation procedure without serious perioperative complications.Transiently elevated WBC count and amylase were observed at 24 h post-IRE,suggesting an acute pancreatic tissue damage which was confirmed by pathological observations.Vascular endothelial cells and pancreatic duct epithelial cells in ablation zone were also positive in terminal deoxynucleotidyl transferase dUTP nick end labeling staining.There was extensive duodenum mucosa damage with local hemorrhage 24 h after ablation,while regeneration of new villous structures were observed at 7 and 28 d post-IRE.Masson’s trichromatic staining showed that the extracellular matrix was still intact in vessels and pancreatic ducts,and even in the duodenum.CONCLUSION IRE ablation to the pancreatic head may be safe and feasible without long-term damage to the surrounding vital structures.However,risks of stress injuries in acute phase should be taken into consideration to prevent severe perioperative complications.

The relationship between Metrnl and diabetic cardiomyopathy and its related molecular mechanism

Objective:To investigate the changes of serum concentration of Metrnl in diabetic cardiomyopathy mice,and the relationship between Metrnl and Diabetic cardiomyopathy(DCM)and its molecular mechanism.Methods:Fifteen male mice were randomly divided into experimental group(DCM+Metrnl),model group(DCM)and control group.Metrnl concentration was measured with an enzyme-linked immunosorbent assay.The experimental group was treated with Metrnl,and the control group and model group were treated with equal volume solvent.Then the myocardial pathological changes,reactive oxygen species and the expression of PPARs and GLUT4 protein and the expression of CD36 and SOD gene were observed after 7 days of administration of recombinant Metrnl.Results:Serum Metrnl concentrations were elevated in DCM(P>0.05).Metrnl reduced the serum concentrations of total cholesterol(TG,P<0.05),triglyceride(TC,P<0.05)and low density lipoprotein cholesterol(LDL-C,P<0.05),while increased high density lipoprotein cholesterol(HDL-C,P<0.05)in DCM.In addition,Metrnl improved the energy metabolism of DCM,decreased the production of reactive oxygen species(ROS)and up-regulated the protein expressions of PPAR-a,PPAR-β/δ,GLUT4 and the expression of SOD in cardiomyocytes,while CD36 gene expression was down-regulated.Conclusion:Serum Metrnl concentrations were elevated in DCM mouse modles.Metrnl improved lipid metabolism and cardiac function in DCM.Besides,it can reduced myocardial oxidative stress injury through PPAR-β/δ,GLUT4 pathway.

The key target of neuroprotection after the onset of ischemic stroke: secretory pathway Ca^(2+)-ATPase 1

The regulatory mechanisms of cytoplasmic Ca2＋ after myocardial infarction-induced Ca2＋ overload involve secretory pathway Ca2＋-ATPase 1 and the Golgi apparatus and are well understood. However, the effect of Golgi apparatus on Ca2＋ overload after cerebral ischemia and reperfusion remains unclear. Four-vessel occlusion rats were used as animal models of cerebral ischemia. The expression of secretory pathway Ca2＋-ATPase 1 in the cortex and hippocampus was detected by immunoblotting, and Ca2＋ concentrations in the cytoplasm and Golgi vesicles were determined. Results showed an overload of cytoplasmic Ca2＋ during ischemia and reperfusion that reached a peak after reperfusion. Levels of Golgi Ca2＋ showed an opposite effect. The expression of Golgi-specific secretory pathway Ca2＋-ATPase 1 in the cortex and hippocampus decreased before ischemia and reperfusion, and increased after reperfusion for 6 hours. This variation was similar to the alteration of calcium in separated Golgi vesicles. These results indicate that the Golgi apparatus participates in the formation and alleviation of calcium overload, and that secretory pathway Ca2＋-ATPase 1 tightly responds to ischemia and reperfusion in nerve cells. Thus, we concluded that secretory pathway Ca2＋-ATPase 1 plays an essential role in cytosolic calcium regulation and its expression can be used as a marker of Golgi stress, responding to cerebral ischemia and reperfusion. The secretory pathway Ca2＋-ATPase 1 can be an important neuroprotective target of ischemic stroke.

Investigation of acupuncture in improving sleep,cognitive and emotion based on attenuation of oxidative stress in prefrontal cortex in sleep-deprived rats

Objective To explore whether acupuncture can improve sleep disturbance,cognitive impairment and emotional disorders caused by sleep deprivation,and its association with the attenuation of oxidative stress injury in prefrontal cortex.Methods Fifty-two male Sprague-Dawley rats were randomly divided into a control group(n=10),a model group(n=14),a manual acupuncture(MA)group(n=14),and a sham-MA group(n=14).All the groups were established as sleep deprivation models via the modified multiple platform method,except for the control group.Rats in both the MA group and the sham-MA group received corresponding intervention,respectively.After modeling and intervention,the four groups received three behavioral tests,namely sleep monitoring,by comprehensive lab animal monitoring system(CLAMS),Morris water maze(MWM)test and open-field test(OFT),followed by oxygen free radical level test and Western blot(WB)detection for the expression levels of Bax and Bcl-2.Results The MA group derived more sleep time within 24 h than either the model group or the sham-MA group(both P<0.05).On MWM orientation navigation test day 1,there were no significant differences in escape latency among the control,MA and sham-MA groups(P>0.05),and the escape latency was significantly shorter in these three groups than that in the model group(all P<0.05).On test day 4,the escape latency was markedly shorter in the MA group than that in either the model group or the sham-MA group(both P<0.05);meanwhile,the MA group showed significantly better performance compared with these two groups in space probe test(both P<0.05).In OFT,compared with the control group,there was a significant decline in the horizontal movement score in the other three groups(all P<0.05),and the decrease was more significant in the model group and the sham-MA group than that in the MA group(both P<0.05).The superoxide dismutase(SOD)content was markedly higher and the malondialdehyde(MDA)content was markedly lower in the MA group than those in the model group and the sham-MA group(all P<0.05).Compared with the model group and the sham-MA group,the expression of Bax was significantly lower and the expression of Bcl-2 was significantly higher in the MA group(all P<0.05).Conclusion MA therapy can lengthen the sleep time in sleep-deprived rats and improve learning and memory impairments induced by sleep deprivation,and the underlying mechanism may be associated with the enhancement of antioxidant capacity in the prefrontal cortex and the inhibition of hippocampal neuronal apoptosis.

7,8-dihydroxyflavone protects human renal proximal tubular cells from hypoxia injury via inhibiting endoplasmic reticulum stress

Objective To observe the effects of 7,8-dihydroxyflavone(7,8-DHF)on hypoxia induced endoplasmic reticulum stress(ERS)in human proximal tubular epithelial cells(HK-2).Methods The mRNA level of ERS associated biomarkers was evaluated by RT-PCR assay

Ferulic acid prevents liver injury and increases the anti-tumor effect of diosbulbin B in vivo

The present study is designed to investigate the protection by ferulic acid against the hepatotoxicity induced by diosbulbin B and its possible mechanism, and further observe whether ferulic acid augments diosbulbin B- induced anti-tumor activity. The results show that ferulic acid decreases diosbulbin B-increased serum alanine transaminase/aspartate transaminase （ALT/AST） levels. Ferulic acid also decreases lipid peroxide （LPO） levels which are elevated in diosbulbin B-treated mice. Histological evaluation of the liver demonstrates hydropic degeneration in diosbulbin B-treated mice, while ferulic acid reverses this injury. Moreover, the activities of copper- and zinc-containing superoxide dismutase （CuZn-SOD） and catalase （CAT） are decreased in the livers of diosbulbin B-treated mice, while ferulic acid reverses these decreases. Further results demonstrate that the mRNA expressions of CuZn-SOD and CAT in diosbulbin B-treated mouse liver are significantly decreased, while ferulic acid prevents this decrease. In addition, ferulic acid also augments diosbulbin B-induced tumor growth inhibition compared with diosbulbin B alone. Taken together, the present study shows that ferulic acid prevents diosbulbin B-induced liver injury via ameliorating diosbulbin B-induced liver oxidative stress injury and augments diosbulbin B-induced anti-tumor activity.

Chlorogenic acid prevents acetaminophen-induced liver injury: the involvement of CYP450 metabolic enzymes and some antioxidant signals

Chlorogenic acid（CGA）, a polyphenolic compound, is abundant in fruits, dietary vegetables, and some medicinal herbs. This study investigated the prevention of CGA against acetaminophen（AP）-induced hepatotoxicity and its engaged mechanisms. CGA reversed the decreased cell viability induced by AP in L-02 cells in vitro. In addition, CGA reduced the AP-induced increased serum levels of alanine/aspartate aminotransferase（ALT/AST） in vivo. The effect of CGA on cytochrome P450（CYP） enzymatic（CYP2E1, CYP1A2, and CYP3A4） activities showed that CGA caused very little inhibition on CYP2E1 and CYP1A2 enzymatic activities, but not CYP3A4. The measurement of liver malondialdehyde（MDA）, reactive oxygen species（ROS）, and glutathione（GSH） levels showed that CGA prevented AP-induced liver oxidative stress injury. Further, CGA increased the AP-induced decreased m RNA expression of peroxiredoxin（Prx） 1, 2, 3, 5, 6, epoxide hydrolase（Ephx） 2, and polymerase（RNA） II（DNA directed） polypeptide K（Polr2k）, and nuclear factor erythroid-2-related factor 2（Nrf2）. In summary, CGA ameliorates the AP-induced liver injury probably by slightly inhibiting CYP2E1 and CYP1A2 enzymatic properties. In addition, cellular important antioxidant signals such as Prx1, 2, 3, 5, 6, Ephx2, Polr2 k, and Nrf2 also contributed to the protection of CGA against AP-induced oxidative stress injury.

Blast-induced traumatic brain injury： a new trend of blast injury research

Blast injury has become the major life- and function-threatening injuries in recent warfares. There is increased research interest in the mental disorders caused by blast-induced traumatic brain injury （bTBI）, which has been proved as one of the ＂signature wounds＂ in modern battlefield. We reviewed the recent progresses in bTBl-related researches and concluded that the new era of blast injury research has shifted from the traditional physical impairments to cognitive dysfunctional/mental disorders that are proved to be more related to the outcome of combat casualty care.

Dangfei Liganning Capsules (当飞利肝宁胶囊) Attenuate the Susceptibility of Rat Nonalcoholic Fatty Liver to Carbon Tetrachloride Toxicity

Objective: To test whether nonalcoholic hepatic steatosis sensitizes carbon tetrachloride (CCl4)-induced liver injury, and to assess the therapeutic effect of Chinese medicine extracts of Dangfei Liganning capsules (当飞利肝宁胶囊) and their potential underlying mechanisms. Methods: Male Wistar rats were fed a high-fat diet to induce nonalcoholic fatty liver disease (NAFLD) or a normal diet (N). Eight weeks later, a nonlethal dose of CCl4 was applied intraperitoneally. From the start, HF-CCl4 rats were administered daily Dangyao extracts (D), Dangfei Liganning capsules (DF), or Diammonium Glycyrrhizinate (G) intragastrically. Rats were sacrificed 48 h after CCl4 administration. In addition to serum biochemistry, liver histopathology was observed using hematoxylin-eosin (HE) and oil red O staining, and hepatic levels of triglyceride (TG), malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), caspase-3 activation and cytochrome P450 (CYP2E1) expression were assessed. Results: There was almost no response to the nonlethal dose of CCl4 in the N control group. However, the HF group demonstrated massive steatosis, and elevated levels of serum ALT and AST, liver MDA, CYP2E1, and caspase-3 activation, whereas the levels of GSH and SOD were significantly decreased. All indexes assessed were dramatically worse in the HF-CCl4 group compared to the HF group, in addition to the more severe steatosis, hepatocyte ballooning, and inflammatory infiltration apparent in the centrilobular area. The medicines we tested affected the pathological changes in HF-CCl4 rats to differing degrees: DF and G led to improvements in all of the above examined indexes, including an obvious improvement in histopathology, and DF improved serum ALT and MDA levels more markedly than G, whereas D extracts produced only mild liver injury attenuation. Conclusion: Liver with NAFLD is more sensitive to hepatotoxicity; furthermore, the disrupted balance of oxidative stress and anti-oxidant defense contributes to the underlying mechanisms. Dangfei Liganning capsules potentially decrease this toxic susceptibility and alleviate liver injury in non-alcoholic fatty liver.