Lung-protective ventilation worsens ventilator-induced diaphragm atrophy and weakness.

BACKGROUND: Lung-protective ventilation (LPV) has been found to minimize the risk of ventilator-induced lung injury (VILI). However, whether LPV is able to diminish ventilator-induced diaphragm dysfunction (VIDD) remains unknown. This study was designed to test the hypothesis that LPV protects the diaphragm against VIDD. METHODS: Adult male Wistar rats received either conventional mechanical (tidal volume [VT]: 10 ml/kg, positive end-expiratory pressure [PEEP]: 2 cm H2O; CV group) or lung-protective (VT: 5 ml/kg, PEEP: 10 cm H2O; LPV group) ventilation for 12 h. Then, diaphragms and lungs were collected for biochemical and histological analyses. Transcriptome sequencing (RNA-seq) was performed to determine the differentially expressed genes in the diaphragms between groups. RESULTS: Our results suggested that LPV was associated with diminished pulmonary injuries and reduced oxidative stress compared with the effects of the CV strategy in rats. However, animals that received LPV showed increased protein degradation, decreased cross-sectional areas (CSAs) of myofibers, and reduced forces of the diaphragm compared with the same parameters in animals receiving CV (p < 0.05). In addition, the LPV group showed a higher level of oxidative stress in the diaphragm than the CV group (p < 0.05). Moreover, RNA-seq and western blots revealed that the peroxisome proliferator-activated receptor γ coactivator-1alpha (PGC-1α), a powerful reactive oxygen species (ROS) inhibitor, was significantly downregulated in the LPV group compared with its expression in the CV group (p < 0.05). CONCLUSIONS: Compared with the CV strategy, the LPV strategy did not protect the diaphragm against VIDD in rats. In contrast, the LPV strategy worsened VIDD by inducing oxidative stress together with the downregulation of PGC-1α in the diaphragm. However, further studies are required to determine the roles of PGC-1α in ventilator-induced diaphragmatic oxidative stress.

Quality retention of chest compression after repetitive practices with or without feedback devices: A randomized manikin study.

OBJECTIVES: This study was designed to investigate whether an audiovisual feedback (AVF) device is beneficial for quality retention of chest compression (CC) after repetitive practices (RP). METHODS: After completion of a 45-min CC-only cardiopulmonary resuscitation (CPR) training, participants performed 3 sessions of practices on days 1, 3, and 7 under the guidance of an instructor with (RP + AVF) or without (RP) the AVF device. CC quality was determined after each session and was retested at 3 and 12 months. RESULTS: In total, ninety-seven third year university students participated in this study. CC quality was improved after 3 sessions in both the RP and RP + AVF groups. Retests at 3 months showed that the proportions of appropriate CC rate and correct hand position were significantly decreased in the RP group as compared with the last practice (p < 0.05). However, no significant changes in CC quality were observed in the RP + AVF group. However, the proportions of appropriate CC rate, depth, and complete recoil were significantly decreased after 12 months in both RP and RP + AVF groups (p < 0.05). There were no significant differences in these parameters between the RP and the RP + AVF groups at 12 months after RP. CONCLUSION: With RP, the use of an AVF device further improves initial CC skill acquisition and short-term quality retention. However, long-term quality retention is not statistically different between rescuers who receive verbal human feedback only and those who receive additional AVF device feedback after RP.

Hemorrhagic Shock Sensitized the Diaphragm to Ventilator-Induced Dysfunction through the Activation of IL-6/JAK/STAT Signaling-Mediated Autophagy in Rats.

Mechanical ventilation (MV) is a major life support technique for the management of trauma-associated hemorrhagic shock (HS). Ventilator-induced diaphragm dysfunction (VIDD), one of the most common complications of MV, has been well demonstrated in animal and human studies. However, few data are available concerning the effects of MV on diaphragm function in HS victims. In the present study, we found diaphragm muscle atrophy and weakness in HS but not in healthy animals after 4 hours of MV. The inhibition of autophagy resulted in reduced muscle fiber atrophy and improved forces. In addition, we observed diaphragmatic interleukin- (IL-) 6 overexpression and activation of its downstream signaling JAK/STAT in HS animals after MV, and either the neutralization of IL-6 or the inhibition of the JAK/STAT pathway attenuated autophagy, diaphragm atrophy, and weakness. Importantly, treatment with nonselective antioxidant exerted no protective effects against VIDD in HS animals. In addition, in vitro study showed that exogenous IL-6 was able to induce activation of JAK/STAT signaling and to increase autophagy in C2C12 cells. Moreover, the inhibition of JAK/STAT signaling abolished IL-6-induced cell autophagy. Together, our results suggested that HS sensitized the diaphragm to ventilator-induced atrophy and weakness through the activation of IL-6/JAK/STAT signaling-mediated autophagy in rats.

Effect of bed width on the quality of compressions in simulated resuscitation: a randomized crossover manikin study.

OBJECTIVES: To investigate the effects of bed width on the quality of chest compressions during simulated in-hospital resuscitation. METHODS: Each candidate performed two 2-minute cycles of compression-only cardiopulmonary resuscitation on an adult manikin placed on either an emergency stretcher (narrow bed) or a standard hospital bed (wide bed) in random order at 1 day intervals. We conducted subjective assessments of cardiopulmonary resuscitation quality and rescuer fatigue at the end of each session, using surveys. RESULTS: There were no significant differences between narrow and wide bed sessions in either mean depth or the percentage of compressions with adequate depth (P=.56 and .58, respectively). The mean rate of compressions and the percentage of compressions with adequate rate were also similar between sessions (P=.24 and .27, respectively). However, the percentage of correct hand position and complete chest recoil was significantly higher in the narrow bed session than in the wide bed session (P=.02 and .02, respectively). In addition, survey results showed that rescuers felt more comfortable and less exhausted in the narrow bed session compared with the wide bed session (P<.001 and < .001). CONCLUSIONS: When rescuers performed chest compressions on an emergency stretcher, chest compression quality increased, and the fatigue of rescuers decreased compared with a standard hospital bed. Therefore, we propose a narrow bed for critically ill inpatients with high risk of cardiac arrest.

MOF-Derived Porous Co3O4 Hollow Tetrahedra with Excellent Performance as Anode Materials for Lithium-Ion Batteries.

Porous Co3O4 hollow tetrahedra were prepared through the thermolysis of metal-organic frameworks and presented reversible capacities of 1196 and 1052 mAh g(-1) at 50 and 200 mA g(-1) after 60 charge/discharge cycles, respectively. Such excellent performances stem from the well-defined hollow structure of Co3O4 tetrahedra.

Dominant hand position improves the quality of external chest compression: a manikin study based on 2010 CPR guidelines.

BACKGROUND: The 2010 cardiopulmonary resuscitation (CPR) guidelines increased the importance of external chest compression. However, the best hand position to be the compressing one has not been identified. OBJECTIVES: To investigate the effects of dominant or nondominant external chest compression hand position during CPR. METHODS: Medical students performed five cycles of conventional CPR and completed one questionnaire. The CPR performances were manually evaluated, and detailed aspects of the external chest compression quality were assessed via the SimMan® Essential system (Laerdal China Ltd., Hangzhou, China). RESULTS: One hundred fifty-seven students participated in the nondominant hand (NH) group, and 68 students participated in the dominant hand (DH) group. The manual evaluations revealed no differences between the two groups. The proportion of chest compressions "above 100 cpm [compressions per minute]" was higher in the DH group than in the NH group (97% vs. 92%, respectively, p = 0.002). The frequency distributions of the chest compression rates were also significantly different between the two groups (p < 0.0001). The distribution of the NH group was concentrated within "130-139" cpm, whereas this distribution was concentrated within "140-149" cpm in the DH group. The chest compression depth of the DH group was deeper than that of the NH group (p = 0.001). The depth of the fifth cycle was significantly decreased compared with those of cycles 1, 2, and 3 in the NH group. A greater number of full chest recoils were observed in the NH group (p = 0.02). CONCLUSION: The dominant hand position during CPR was associated with a higher chest compression rate, a greater chest compression depth, and delayed fatigue.

Medical students do not adversely affect the quality of cardiopulmonary resuscitation for ED patients.

OBJECTIVES: To investigate the effect of medical student involvement on the quality of actual cardiopulmonary resuscitation (CPR). METHODS: A digital video-recording system was used to record and analyze CPR procedures for adult patients from March 2011 to September 2012. RESULTS: Twenty-six student-involved and 40 non-student-involved cases were studied. The chest compression rate in the student-involved group was significantly higher than that in the non-student-involved group (P < .001). The proportion of compressions at "above 110 cpm" was higher in the student-involved group (P = .021), whereas the proportion at "90-110 cpm" was lower in the student-involved group (P = .015). The ratio of hands-off time to total manual compression time was significantly lower in the student-involved group than in the non-student-involved group (P = .04). In contrast, the student-involved group delivered a higher ventilation rate compared with the non-student-involved group (P = .02). The observed time delay to first compression and first ventilation were very similar between the groups. There were no significant differences between the groups in either return of spontaneous circulation or time from survival to discharge. CONCLUSION: Student-involved resuscitation teams were able to perform good CPR, with higher compression rates and fewer interruptions. However, the supervision from medical staff is still needed to ensure appropriate chest compression and ventilation rate in student-involved actual CPR in the emergency department.

Protective effects of lipoxin A4 in testis injury following testicular torsion and detorsion in rats.

PURPOSE: To investigate the protective effects of lipoxin A4 (LXA4) in rat testis injury following testicular torsion/detorsion. METHODS: A rat testicular torsion model has been established as described. Rats were randomly divided into 6 groups: sham group, torsion group, torsion/detorsion (T/D) group, and T/D plus LXA4-pretreated groups (3 subgroups). Rats in LXA4-pretreated groups received LXA4 injection (0.1, 1.0, and 10 µg/kg body weight in LXA4-pretreated subgroups 1-3, resp.) at a single dose 1 h before detorsion. Biochemical analysis, apoptosis assessment, and morphologic evaluation were carried out after orchiectomies. RESULTS: GPx and SOD levels significantly increased and MDA levels significantly reduced in LXA4-pretreated groups compared to T/D group. LXA4 also reverted IL-2 and TNF- α to basal levels and improved the expression of IL-4 and IL-10 in LXA4-pretreated groups. Moreover, the expression of NF- κ B was downregulated in LXA4-pretreated groups. LXA4 treatment also showed an improved testicular morphology and decreased apoptosis in testes. CONCLUSION: Lipoxin A4 protects rats against testes injury after torsion/detorsion via modulation of cytokines, oxidative stress, and NF- κ B activity.

Sedation with midazolam worsens the diaphragm function than dexmedetomidine and propofol during mechanical ventilation in rats.

BACKGROUND: Mechanical ventilation (MV) is identified as an independent contributor to diaphragmatic atrophy and contractile dysfunction. Appropriate sedation is also essential during MV, and anesthetics may have direct adverse effects on the diaphragm. However, there is a lack of research into the effects of different anesthetics on diaphragm function during MV. OBJECTIVES: In the present study, we aim to examine the effect of midazolam, dexmedetomidine, and propofol on diaphragm function during MV. DESIGN: Animal study. SETTING: University research laboratory. SUBJECTS: Male Wistar rats. INTERVENTIONS: Animals were experienced 12 h of MV or spontaneous breathing (SB) with continuous anesthetics infusion. Diaphragm contractile properties, cross-sectional areas, microcirculation, oxidative stress, and proteolysis were examined. MEASUREMENTS AND MAIN RESULTS: Diaphragmatic specific force was markedly reduced in the midazolam group compared with the dexmedetomidine (-60.4 ±â€¯3.01%, p < 0.001) and propofol group (-58.3 ±â€¯2.60%, p < 0.001) after MV. MV sedated with midazolam induced more atrophy of type II fibers compared with dexmedetomidine (-21.8 ±â€¯2.11%, p = 0.0001) and propofol (-8.2 ±â€¯1.53%, p = 0.003). No significant differences of these indices were found in the midazolam, dexmedetomidine, and propofol groups under SB condition (all p > 0.05, respectively). Twelve hours of MV resulted in a time dependent reduction in diaphragmatic functional capillary density (PB -25.1%, p = 0.0001; MZ -21.6%, p = 0.0003; DD -15.2%, p = 0.022; PP -24.8%, p = 0.0001, respectively), which did not occur in the gastrocnemius muscle. The diaphragmatic lipid peroxidation adducts 4-HNE and HIF-1α levels were significantly lower in dexmedetomidine group and propofol group compared to midazolam group (p < 0.05, respectively). Meanwhile, the catalase and SOD levels were also relatively lower (p < 0.05, respectively) in midazolam group compared to dexmedetomidine group and propofol group. CONCLUSIONS: Twelve hours of mechanical ventilation during midazolam sedation led to a more severe diaphragm dysfunction than dexmedetomidine and propofol, possibly caused by its relative weaker antioxidant capacity.

Effect of Mild Hypothermia on the Diaphragmatic Microcirculation and Function in A Murine Cardiopulmonary Resuscitated Model.

OBJECTIVE: Diaphragm dysfunction often occurs in patients with prolonged mechanical ventilation (MV) after resuscitation. Mild hypothermia (MHT) is a classical treatment to improve the outcomes of cardiac arrest (CA); however, the effect of MHT on diaphragm function remains unclear. In the present study, we aim to investigate the effect of MHT on diaphragmatic microcirculation and function using a murine cardiopulmonary resuscitation model. METHODS: Thirty-two rats were randomly assigned into a resuscitation normothermia group (RNT), an intraresuscitation hypothermia group (IRH), a postresuscitation hypothermia group (PRH), or a sham control group. CA was induced by airway occlusion, and resuscitation was implemented by precordial compression and MV. The diaphragmatic microvascular blood flow velocity, diaphragmatic microcirculation flow index (MFI), and perfused vascular density (PVD) were measured. The diaphragm was then removed for in vitro contractile property examination and cross-sectional area measurement. The lipid peroxidation and superoxide dismutase (SOD) levels in the diaphragm were also assayed. RESULTS: Either early or delayed MHT intervention did not improve the diaphragmatic microvascular blood flow velocity, MFI, and PVD, which were significantly decreased during prolonged MV after resuscitation. Compared with the RNT group, treatment with MHT increased the diaphragm contractility, fiber dimensions, and SOD levels and decreased diaphragm lipid peroxidation. A more significant change in these indices was observed in the IRH group compared with that in the PRH group. CONCLUSION: MHT preserves the diaphragm contractility and fiber dimensions and decreases oxidative stress but does not improve the microcirculatory blood supply during prolonged MV after resuscitation. Early MHT intervention is more efficient in preventing diaphragm dysfunction than delayed intervention after CA.

The association between markers of liver injury and clinical outcomes in patients with COVID-19 in Wuhan.

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) is a critical challenge for public health. The effect of COVID-19 on liver injury has not been fully established. AIMS: To evaluate the dynamic changes in liver function and the relationship between liver damage and prognosis in patients with COVID-19. METHODS: Retrospective analysis of clinical data of 675 patients with COVID-19 in Zhongnan Hospital of Wuhan University from January 3 to March 8, 2020. Patients were classified as having normal or abnormal liver function and liver injury. RESULTS: Of 675 patients, 253 (37.5%) had abnormal liver function during hospitalisation, and 52 (7.7%) had liver injury. The dynamic changes of ALT and AST levels were more significant in patients with liver injury and in those who died. AST >3-fold upper limit of normal (ULN) had the highest risk of death and mechanical ventilation. Compared to patients with normal AST levels, mortality and risk of mechanical ventilation significantly increased 19.27-fold (95% confidence interval [CI], 4.89-75.97; P < 0.0001) and 116.72-fold (95% CI, 31.58-431.46; P < 0.0001), respectively, in patients with AST above 3-fold ULN. Increased leucocytes, decreased lymphocytes and female sex were independently associated with liver injury. CONCLUSIONS: The dynamic changes in liver function may have a significant correlation with the severity and prognosis of COVID-19. Increased index of liver injury was closely related to mortality and need for mechanical ventilation. Therefore, these indicators should be closely monitored during hospitalisation.

Fluid resuscitation with preventive peritoneal dialysis attenuates crush injury-related acute kidney injury and improves survival outcome.

BACKGROUND: In-hospital renal replacement therapy (RRT) is widely used for the treatments of acute kidney injury (AKI) in crush injury (CI) victims. This study was designed to investigate whether preventive peritoneal dialysis (PPD) is useful for renal protection in CI. METHODS: Animals received hindlimb compressions for 6 h to induce CI. Then, animals were untreated or treated with PPD and/or massive fluid resuscitation (MFR) for 8 h since the onset of compression release. Blood and renal tissue samples were collected at various time points for biological and morphological analysis. RESULTS: PPD attenuated lactic acidosis and reduced serum K+ and myoglobin levels in CI animals. In addition, PPD was effective in removing blood urea nitrogen (BUN) and creatinine, and reduced renal expressions of neutrophil gelatinase-associated lipocalin (NGAL). The combination of PPD and MFR furtherly attenuated AKI with significantly decreased histological scores (p = 0.037) and reduced NGAL expressions (p = 0.0002) as compared with the MFR group. Moreover, MFR + PPD group had a significantly higher survival rate than that in the MFR and the PPD groups (p < 0.05, respectively). CONCLUSION: The use of PPD at the onset of compression release is beneficial for renal protection and survival outcome in a rabbit model of CI.

Interactions between Cytosolic Phospholipase A2 Activation and Mitochondrial Reactive Oxygen Species Production in the Development of Ventilator-Induced Diaphragm Dysfunction.

Cytosolic phospholipase A2 (cPLA2) has been reported to be critical for infection-induced mitochondrial reactive oxygen species (ROS) production and diaphragm dysfunction (DD). In the present study, we aim to investigate whether cPLA2 was involved in ventilator-induced diaphragm dysfunction (VIDD). Our results showed that mechanical ventilation (MV) induced cPLA2 activation in the diaphragm with excessive mitochondrial ROS generation and muscle weakness. Specific inhibition of cPLA2 with CDIBA resulted in decreased mitochondrial ROS levels and improved diaphragm forces. In addition, mitochondria-targeted antioxidant MitoTEMPO attenuated ventilator-induced mitochondrial oxidative stress and downregulated cPLA2 activation in vivo. Both CDIBA and MitoTEMPO were able to attenuate protein degradation, muscle atrophy, and weakness following prolonged MV. Furthermore, laser Doppler imaging showed that MV decreased diaphragm tissue perfusion and induced subsequent hypoxia. An in vitro study also demonstrated a positive association between cPLA2 activation and mitochondrial ROS generation in C2C12 cells cultured under hypoxic condition. Collectively, our study showed that cPLA2 activation positively interacts with mitochondrial ROS generation in the development of VIDD, and ventilator-induced diaphragm hypoxia serves as a possible contributor to this positive feedback loop.

Systemic Inflammatory Response and Multiple Organ Dysfunctions Following Crush Injury: a New Experimental Model in Rabbits.

In this study, we aim to develop a new, reproducible crush injury (CI) model in rabbits. Anesthetized rabbits were compressed on both hind limbs using a special instrument for 6 h followed by 3 h of reperfusion. Blood samples and injured muscles were collected for biochemical analysis and morphological evaluation. Survival observation lasted for 72 h. Bilateral compressions with 10 kg/kg body weight (BW), but not with 5 kg/kg BW, reduced serious systemic impairment. Bilateral compressions with 10 kg/kg BW resulted in severe lactic acidosis; increased serum K+, creatine phosphokinase, aspartate transaminase, alanine transaminase, blood urea nitrogen, and creatinine levels; and a sharply decreased mean arterial blood pressure after compression release. Serious tissue edema and inflammation were observed in the damaged muscles. The mortality rates in compression groups were 20% (5 kg/kg BW) and 60% (10 kg/kg BW). There was a significant increase in plasma concentrations of TNF-α and IL-1ß after compression. Plasma IL-1ß levels returned to control levels at 6 h after compression release, whereas TNF-α peaked at 12 h following reperfusion. Furthermore, antiinflammatory cytokines, including IL-4 and IL-10, were also increased after compression, and these two cytokines peaked at 12 h after compression release. Our data suggested that bilateral compression with 10 kg/kg BW on rabbits' hind limbs is a reproducible CI model, and we also reported the CI-induced systemic inflammatory responses and changes of cytokines over time.

Acceleration-based training: A new mode of training in senescent rats improving performance and left ventricular and muscle functions.

High intensity training (HIT) has been shown to improve maximal aerobic capacity and muscle protein synthesis but has not yet been investigated in senescent rats. We hypothesized that the change of speed (acceleration) during each bout of HIT acts as a stimulus responsible for the adaptations of the organism to exercise. Twenty two month-old (mo) rats (n=13) were subjected to a short acceleration protocol (20-30min) of exercise, comprising 3 independent bouts of acceleration and compared to an age-matched sedentary group (n=14). The protocol was repeated twice a week for two months. Following the protocol, performance, cardiac function, muscle mechanics, and the cellular and molecular pathways that are implicated in exercise adaptations were investigated. This new training, comprising only 16 sessions, improved maximal oxygen uptake (⩒O2peak; +6.6%, p<0.05), running distance (+95.2%; p<0.001), speed (+29.7%; p<0.01) and muscle function of 24mo rats in only 8weeks. This new training protocol induced cardiac hypertrophy and improved fractional shortening (47.3% vs. 41.1% in the control group, p<0.01) and ejection fraction. Moreover, it also improved the mechanics of skeletal muscle by increasing developed force (+31% vs. the control group, p<0.05) and maximal mechanical efficiency, activated the IGF1/mTOR/Akt pathway, and reduced the Smad2/3 pathway. Our results clearly show that the change in speed is a stimulus to control cardiac and skeletal muscle mass. This acceleration-based training is not time-consuming and may be adaptable for athletes, the elderly or chronic disease patients in order to improve strength, oxidative capacity, and quality of life.

Thalidomide Inhibits TGF-ß1-induced Epithelial to Mesenchymal Transition in Alveolar Epithelial Cells via Smad-Dependent and Smad-Independent Signaling Pathways.

Recent evidence indicates that the epithelial to mesenchymal transition (EMT) in primary alveolar cells (AECs) plays an important role in idiopathic pulmonary fibrosis (IPF). In vivo models have suggested that thalidomide (THL) has anti-fibrotic effects against pulmonary fibrosis, but the underlying mechanism of this effect is not clear. This study investigated whether THL regulates alveolar EMT and the possible mechanisms underlying this process. CCL-149 cells were treated with TGF-ß1 in the presence of THL at the indicated concentrations. EMT was assessed by changes in cell morphology and in phenotypic markers. Signaling pathways involved in EMT were characterized by western blot analysis. THL inhibited the TGF-ß1 induction of α-SMA, vimentin, MMP-2/-9 and collagen type IV expression and restored the morphological changes in primary alveolar epithelial cells caused by TGF-ß1. TGF-ß1 induction of α-SMA expression was partially dependent on the activation of p38, JNK, ERK, Akt, Smad 2 and Smad3. Moreover, THL inhibited TGF-ß1-induced phosphorylation of p38, JNK, ERK, Akt, GSK3ß, Smad 2 and Smad3 without altering the total expression levels of those proteins. These findings indicate that TGF-ß1-induced EMT in alveolar epithelial cells is inhibited by THL via both Smad-dependent and non-Smad-dependent signaling pathways and suggests therapeutic approaches for targeting this process in pulmonary fibrosis.

Embelin Reduces Systemic Inflammation and Ameliorates Organ Injuries in Septic Rats Through Downregulating STAT3 and NF-κB Pathways.

Current evidence shows that the majority of the damage induced during sepsis is pursuant to induction and overproduction of endogenous cytokines. Embelin has been reported to suppress cytokine expressions in inflammatory disorders. The present study was designed to investigate the effects of embelin on cecal and ligation and puncture (CLP)-induced rat sepsis. Single-dose administration of embelin 1 h after surgery significantly improved survival of rats with CLP-induced sepsis. In addition, embelin treatment reduced the serum levels of pro-inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6 and decreased organ inflammation and injuries. Moreover, embelin suppressed the activation of p65 subunit of nuclear factor-kappa B (NF-κB) and signal transducers and activators of transcription 3 (STAT3). Collectively, these results indicated that embelin ameliorates sepsis in rats through suppressing STAT3 and NF-κB pathways.

Triptolide attenuates cerebral ischemia and reperfusion injury in rats through the inhibition the nuclear factor kappa B signaling pathway.

Inflammation plays critical roles in the acute progression of the pathology of ischemic injury. Previous studies have shown that triptolide interferes with a number of pro-inflammatory mechanisms. In this study, we investigated whether triptolide has protective effects during acute cerebral ischemia/reperfusion (I/R) injury. Male Sprague Dawley rats received triptolide or vehicle at the onset of reperfusion following middle cerebral artery occlusion. Twenty-four hours after reperfusion, we evaluated neurological injuries, the expression of pro-inflammatory markers, and NF-κB activation. I/R rats treated with triptolide showed significantly better neurological deficit scores, decreased neural apoptosis, and reduced cerebral infarct volume and brain edema, and triptolide treatment suppressed the activation of NF-κB following I/R injury. Furthermore, the expression levels of pro-inflammatory cytokines at both the mRNA and protein levels were significantly decreased in rats receiving triptolide. These results indicate that the neuroprotective effects of triptolide during acute cerebral I/R injury are possibly related to the inhibition of both the NF-κB signaling pathway and inflammation.

Kaempferol pretreatment modulates systemic inflammation and oxidative stress following hemorrhagic shock in mice.

BACKGROUND: Kaempferol has been reported as beneficial for both acute and chronic inflammatory diseases. This study aims to investigate whether kaempferol affects systemic inflammation and oxidative stress in the heart, lung, and liver after hemorrhagic shock in mice. METHODS: Male C57/BL6 mice underwent hemorrhagic shock (mean arterial pressure of 35 mmHg for 90 min) and were arbitrarily divided into Sham, hemorrhagic shock (HS), and Kae groups (n = 10 in each group). Mice in the Kae groups received a kaempferol (10-mg/kg body weight) injection 12 h prior to (Group Kae PT) or 90 min after (Group Kae T) the initiation of hemorrhagic shock. Plasma proinflammatory cytokines (TNF-α and IL-6), organ myeloperoxidase (MPO) and superoxide dismutase (SOD) activities, and organ malondialdehyde (MDA) concentrations and heme oxygenase-1 (HO-1) expression levels were assessed by enzyme-linked immunosorbent assay (ELISA) or western blot assay. RESULTS: Compared with the HS group and the Kae T group, pretreatment with kaempferol significantly decreased proinflammatory cytokines TNF-α (P = 0.012 and 0.015, respectively) and IL-6 (P = 0.023 and 0.014, respectively) following hemorrhagic shock. Kae pretreatment reverted MPO, SOD, and MDA to basal levels in the heart, lung, and liver (Ps < 0.05), while the Kae T group showed no significant differences in these biomarkers compared with the HS group (Ps > 0.05). HO-1 expression was significantly increased in the Kae PT group compared with the other groups (P = 0.011 vs. HS group and P = 0.02 vs. Kae T group). CONCLUSIONS: Pretreatment of hemorrhagic shock mice with kaempferol significantly decreased plasma levels of TNF-α and IL-6; reverted MPO, SOD, and MDA in the heart, lung, and liver; and increased expression of HO-1 in the same organs.