SS-31 inhibits the inflammatory response by increasing ATG5 and promoting autophagy in lipopolysaccharide-stimulated HepG2 cells.

SS-31 is a mitochondria-targeting short peptide. Recent studies have indicated its hepatoprotective effects. In our study, we investigated the impact of SS-31 on LPS-induced autophagy in HepG2 cells. The results obtained from a dual-fluorescence autophagy detection system revealed that SS-31 promotes the formation of autolysosomes and autophagosomes, thereby facilitating autophagic flux to a certain degree. Additionally, both ELISA and qPCR analyses provided further evidence that SS-31 safeguards HepG2 cells against inflammatory responses triggered by LPS through ATG5-dependent autophagy. In summary, our study demonstrates that SS-31 inhibits LPS-stimulated inflammation in HepG2 cells by upregulating ATG5-dependent autophagy.

Adsorption of Sb(III) and Pb(II) in wastewater by magnetic γ-Fe2O3-loaded sludge biochar: Performance and mechanisms.

Magnetically modified carbon-based adsorbent (BC@γ-Fe2O3) was prepared through facile route using activated sludge biomass and evaluated for the simultaneous removal of Sb(III) and Pb(II). BC@γ-Fe2O3 exhibited outstanding Sb(III) and Pb(II) adsorption capacity when 200 mg of adsorbent was employed at pH 5.0 for 240 min, with the removal efficiency higher than 90%. The experiments demonstrated the excellent reusability and the potent anti-interference properties of the prepared absorbent. Freundlich and pseudo-second-order kinetic were prior to describe the adsorption process. The adsorption of Sb(III) and Pb(II) onto BC@γ-Fe2O3 was spontaneous and endothermic. BC@γ-Fe2O3 with high specific surface area revealed the exceptional competence to absorb Sb(III) and Pb(II) through pore filling, electrostatic adsorption and complexation. The adsorption mechanisms of Sb(III) and Pb(II) showed similarities with slight disparities. The removal of Sb(III) involved the Fe-O-Sb bond and π-π bond, while the adsorption of Pb(II) was closely related to ion exchange. Moreover, Sb(III) was oxidized to Sb(V) in a minor part during adsorption. The Fe-O-Cl active sites on BC allowed for the binding of γ-Fe2O3, guaranteeing the abundant adsorption sites and stability. BC@γ-Fe2O3 provides an efficient and green insight into the simultaneous removal of complex heavy metals with promising application in wastewater treatment.

Daidzein alleviates osteoporosis by promoting osteogenesis and angiogenesis coupling.

Background: Postmenopausal osteoporosis and osteoporosis-related fractures are world-wide serious public health problem. Recent studies demonstrated that inhibiting caveolin-1 leads to osteoclastogenesis suppression and protection against OVX-induced osteoporosis. This study aimed to explore the mechanism of caveolin-1 mediating bone loss and the potential therapeutic target. Methods: Thirty C57BL/6 female mice were allocated randomly into three groups: sham or bilateral ovariectomy (OVX) surgeries were performed for mice and subsequently daidzein or vehicle was administrated to animals (control, OVX + vehicle and OVX + daidzein). After 8-week administration, femurs were harvested for Micro-CT scan, histological staining including H&E, immunohistochemistry, immunofluorescence, TRAP. Bone marrow endothelial cells (BMECs) were cultured and treated with inhibitors of caveolin-1 (daidzein) or EGFR (erlotinib) and then scratch wound healing and ki67 assays were performed. In addition, cells were harvested for western blot and PCR analysis. Results: Micro-CT showed inhibiting caveolin-1with daidzein alleviated OVX-induced osteoporosis and osteogenesis suppression. Further investigations revealed H-type vessels in cancellous bone were decreased in OVX-induced mice, which can be alleviated by daidzein. It was subsequently proved that daidzein improved migration and proliferation of BMECs hence improved H-type vessels formation through inhibiting caveolin-1, which suppressed EGFR/AKT/PI3K signaling in BMECs. Conclusions: This study demonstrated that daidzein alleviates OVX-induced osteoporosis by promoting H-type vessels formation in cancellous bone, which then promotes bone formation. Activating EGFR/AKT/PI3K signaling could be the critical reason.

Heat-Killed Staphylococcus aureus Induces Bone Mass Loss through Telomere Erosion.

The mechanism of systemic osteoporosis caused by chronic infection is not completely clear, and there is a lack of reasonable interventions for this disease. In this study, heat-killed S. aureus (HKSA) was applied to simulate the inflammation caused by the typical clinical pathogen and to explore the mechanism of systemic bone loss caused by it. In this study, we found that the systemic application of HKSA caused bone loss in mice. Further exploration found that HKSA caused cellular senescence, telomere length shortening, and telomere dysfunction-induced foci (TIF) in limb bones. As a well-known telomerase activator, cycloastragenol (CAG) significantly alleviated HKSA-induced telomere erosion and bone loss. These results suggested that telomere erosion in bone marrow cells is a possible mechanism of HKSA-induced bone loss. CAG may protect against HKSA-induced bone loss by alleviating telomere erosion in bone marrow cells.

Long non-coding RNA X-inactive specific transcript promotes osteosarcoma metastasis via modulating microRNA-758/Rab16.

BACKGROUND: As a common malignant bone sarcoma, osteosarcoma (OS) affects the health and lives of many people. Here, we probed the effects of long non-coding RNA (lncRNA) X-inactive specific transcript (XIST) and microRNA-758 (miR-758) on OS metastasis, and examined possible downstream effector. METHODS: Quantitative reverse transcription PCR (qRT-PCR) was performed to detect the expressions of XIST and miR-758 in OS tissues and cells. Cell transfection was carried out to alter the levels of XIST and miR-758 in OS cells, and cell viability, migration, and invasion were assessed. Subsequently, qRT-PCR and a dual-luciferase reporter assay were conducted to analyze the regulatory effects of XIST on miR-758 and miR-758 on Rab16. Finally, we investigated whether Rab16 was the downstream effector of XIST/miR-758 axis. RESULTS: XIST was highly expressed in OS tissues and cells, but the opposite was seen for miR-758. In OS cells, migration, invasion, and epithelial-mesenchymal transformation (EMT) was promoted by overexpression of XIST and miR-758 inhibitor, but were inhibited by XIST knockdown and miR-758 mimics. XIST regulated miR-758 expression, and miR-758 regulated Rab16 expression in OS cells. Overexpression of Rab16 reversed the effects of miR-758 mimics on OS cell migration and invasion. CONCLUSIONS: XIST contributed to OS cell migration, invasion, and EMT via regulation of miR-758/Rab16.

S100B/RAGE/Ceramide signaling pathway is involved in sepsis-associated encephalopathy.

AIMS: Sepsis-associated encephalopathy (SAE) is one of the most common complications of sepsis, and it might lead to long-term cognitive dysfunction and disability. This study aimed to explore the role of S100 calcium binding protein B (S100B)/RAGE/ceramide signaling pathway in SAE. MAIN METHODS: FPS-ZM1 (an inhibitor of RAGE), myriocin and GW4869 (an inhibitor of ceramide) were used to explore the role of S100B/RAGE/ceramide in acute brain injury and long-term cognitive impairment in sepsis. In addition, Mdivi-1 (inhibitor of Drp1) and Drp1 siRNA were utilized to assess the effects of C2-ceramide on neuronal mitochondria, and to explore the specific underlying mechanism in C2 ceramide-induced death of HT22 mouse hippocampal neuronal cells. KEY FINDINGS: Western blot analysis showed that sepsis significantly up-regulated S100B and RAGE. Nissl staining and Morris water maze (MWM) test revealed that inhibition of RAGE with FPS-ZM1 markedly attenuated cecal ligation and puncture (CLP)-induced brain damage and cognitive dysfunction. Furthermore, FPS-ZM1 relieved sepsis-induced C2-ceramide accumulation and abnormal mitochondrial dynamics. Moreover, inhibition of ceramide also showed similar protective effects both in vivo and in vitro. Furthermore, Mdivi-1 and Drp1 siRNA significantly reduced C2-ceramide-induced neuronal mitochondrial fragmentation and cell apoptosis in vitro. SIGNIFICANCE: This study confirmed that S100B regulates mitochondrial dynamics through RAGE/ceramide pathway, in addition to the role of this pathway in acute brain injury and long-term cognitive impairment during sepsis.

MicroRNA-125b alleviates hydrogen-peroxide-induced abnormal mitochondrial dynamics in HT22 cells by inhibiting p53.

Micro-RNA125b (miR-125b) and tumor protein p53 (p53) are involved in the regulation of mitochondrial dynamics; however, the mechanism of their possible interaction during oxidative stress remains unclear. In this study, we investigated the role and mechanism of miR-125b and p53 in oxidative stress-induced mitochondrial damage in immortalized mouse hippocampal HT22 cells. Following stimulation with H2O2, we observed downregulation of miR-125b expression, upregulation of p53 expression, mitochondria were damaged and increased cell death. Overexpression of miR-125b alleviated mitochondrial damage and inhibited p53 expression. Furthermore, confocal and electron microscopy showed that overexpression of p53 eliminated the protective effect of miR-125b on the mitochondria. Thus, miR-125b alleviates abnormal mitochondrial homeostasis in H2O2-treated HT22 cells by suppressing p53 expression. Our data reveal a new model by which miR-125b influences mitochondrial dynamics.

Extracellular Vesicles: A Potential Biomarker for Quick Identification of Infectious Osteomyelitis.

Effective management of infectious osteomyelitis relies on timely microorganism identification and appropriate antibiotic therapy. Extracellular vesicles (EVs) carry protein and genetic information accumulated rapidly in the circulation upon infection. Rat osteomyelitis models infected by Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Escherichia coli were established for the present study. Serum EVs were isolated 3 days after infection. The size and number of serum EVs from infected rats were significantly higher than those from controls. In addition, bacterial aggregation assay showed that the S. aureus and E. coli formed large aggregates in response to the stimulation of serum EVs from S. aureus-infected and E. coli-infected rats, respectively. Treatment of EVs-S. epidermidis led to large aggregates of S. epidermidis and E. coli, whereas stimulation of EVs-P. aeruginosa to large aggregates of S. aureus and P. aeruginosa. To evaluate the changes in EVs in osteomyelitis patients, 28 patients including 5 S. aureus ones and 21 controls were enrolled. Results showed that the size and number of serum EVs from S. aureus osteomyelitis patients were higher than those from controls. Further analysis using receiver operating characteristic curves revealed that only the particle size might be a potential diagnostic marker for osteomyelitis. Strikingly, serum EVs from S. aureus osteomyelitis patients induced significantly stronger aggregation of S. aureus and a cross-reaction with P. aeruginosa. Together, these findings indicate that the size and number of serum EVs may help in the diagnosis of potential infection and that EVs-bacteria aggregation assay may be a quick test to identify infectious microorganisms for osteomyelitis patients.

Identification of key genes of human bone marrow stromal cells adipogenesis at an early stage.

BACKGROUND: Bone marrow adipocyte (BMA), closely associated with bone degeneration, shares common progenitors with osteoblastic lineage. However, the intrinsic mechanism of cells fate commitment between BMA and osteogenic lineage remains unclear. METHODS: Gene Expression Omnibus (GEO) dataset GSE107789 publicly available was downloaded and analyzed. Differentially expressed genes (DEGs) were analyzed using GEO2R. Functional and pathway enrichment analyses of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were conducted by The Database for Annotation, Visualization and Integrated Discovery and Gene set enrichment analysis software. Protein-protein interactions (PPI) network was obtained using STRING database, visualized and clustered by Cytoscape software. Transcriptional levels of key genes were verified by real-time quantitative PCR in vitro in Bone marrow stromal cells (BMSCs) undergoing adipogenic differentiation at day 7 and in vivo in ovariectomized mice model. RESULTS: A total of 2,869 DEGs, including 1,357 up-regulated and 1,512 down-regulated ones, were screened out from transcriptional profile of human BMSCs undergoing adipogenic induction at day 7 vs. day 0. Functional and pathway enrichment analysis, combined with modules analysis of PPI network, highlighted ACSL1, sphingosine 1-phosphate receptors 3 (S1PR3), ZBTB16 and glypican 3 as key genes up-regulated at the early stage of BMSCs adipogenic differentiation. Furthermore, up-regulated mRNA expression levels of ACSL1, S1PR3 and ZBTB16 were confirmed both in vitro and in vivo. CONCLUSION: ACSL1, S1PR3 and ZBTB16 may play crucial roles in early regulation of BMSCs adipogenic differentiation.

Investigation on Microstructures and Mechanical Properties of the Hypoeutectic Al-10Si-0.8Fe-XEr Alloy.

In this paper, the effect of Er addition (0.2, 0.5, 0.65, 0.8, 1.0, and 1.5 wt. %) on the microstructure evolution and tensile properties of as-cast hypereutectic Al-10Si-0.8Fe alloy was investigated. The phases and their morphologies in these alloys were identified by XRD and SEM equipped with EDX with the help of metallographic analysis techniques; the length of the secondary phase (LSP) and secondary dendrite arm spacing (SDAS) of α-Al grain were quantified. The results indicated that the second phases (primary Si, eutectic Si, and iron-rich phases) and α-Al grain were significantly refined when the addition of Er increased from 0 to 0.8 wt. %. The mean LSP and SADS values were decreased to a minimum value when the Er addition reached 0.8 wt. %. However, the second phases and α-Al grain became coarser when the level of Er increased more than 0.8 wt. %. The analysis of XRD shows that Er mainly exists in the form of Er2Si compound. The microstructure modification also has a significant effect on the mechanical properties of the alloy. The yield strength (YS), ultimate tensile strength (UTS), and elongation (EL) increase from 52.86 MPa, 163.84 MPa, and 3.45% to 71.01 MPa, 163.84 MPa, and 5.65%, respectively. From the fracture surface, the promotions of mechanical properties are due to the dispersion and pinning reinforcement caused by the Er2Si phase.

The dynamic change of serum S100B levels from day 1 to day 3 is more associated with sepsis-associated encephalopathy.

We investigated the role of dynamic changes of serum levels S100B protein in brain injury and poor outcome of sepsis. This is a prospective cohort study designed to include 104 adult patients with sepsis who are admitted to ICU from Jan 2015 to Aug 2016. Sepsis was defined as sepsis 3.0. Patients with a GCS score of <15, or at least one positive CAM-ICU score were thought to have brain dysfunction. 59 patients were diagnosed with SAE and the rest 45 patients were diagnosed with non-SAE. Serum S100B was measured on day 1 and 3 after ICU admission. Primary outcomes included brain dysfunction and 28-day/180-day mortality. The SAE group showed a significantly higher APACHE II score, SOFA scores, length of ICU stay, 28-day and 180-day mortality, serum S100B levels on day 1 and day 3. S100B levels on day 1 of 0.226 µg/L were diagnostic for SAE with 80.0% specificity and 66.1% sensitivity, and the area under (AUC) the curve was 0.728, S100B levels on day 3 of 0.144 µg/L were diagnostic for SAE with 84.44% specificity and 69.49% sensitivity, and the AUC was 0.819. In addition, the AUC for S100B on day 3 for predicting 180-day mortality was larger than for S100B on day 1 (0.731 vs. 0.611). Multiple logistic regression analysis showed that S100B3 (p = 0.001) but not S100B1 (p = 0.927) were independently correlated with SAE. Kaplan-Meier survival analysis showed that patients with S100B levels higher than 0.144 µg/L had a lower probability of survival at day 180. There were more patients with encephalopathy and a higher 28-day or 180-day mortality in the ΔS100B + group than in the ΔS100B- group. Multiple logistic regression analysis showed that SAE and IL-6 on day 3 were independently correlated with S100B dynamic increase. These findings suggest that elevated serum S100B levels on day 3 and the dynamic changes of serum S100B levels from day three to one were more associated with brain dysfunction and mortality than that on day 1 in patients with sepsis.

Amitriptyline Reduces Sepsis-Induced Brain Damage Through TrkA Signaling Pathway.

Sepsis can induce acute and chronic changes in the central nervous system termed sepsis-associated encephalopathy (SAE). Not only cognitive deficits but also anxiety, depression, and post-traumatic stress disorder are common in severe sepsis survivors. In this study, we demonstrated that amitriptyline, a classic tricyclic antidepressant, reduced sepsis-induced brain damage through the tropomyosin receptor kinase A (TrkA) signaling pathway. Amitriptyline ameliorated neuronal loss assessed by Nissl staining in a mouse cecal ligation and puncture (CLP)-induced sepsis model. Furthermore, amitriptyline reduced early gliosis assessed by immunofluorescence and late cognitive deficits assessed by the Morris water maze (MWM) test. Moreover, amitriptyline treatment attenuated oxidative stress indicated by less superoxide dismutase (SOD) and catalase (CAT) activity consumption and malondialdehyde (MDA) accumulation. Interestingly, those protective effects of amitriptyline could be abolished by GW441756, a TrkA signaling pathway inhibitor. Immunoblot directly showed that TrkA signaling pathway-associated proteins, such as Akt and GSK3ß, were involved in the neuroprotective effects of amitriptyline. Thus, amitriptyline appears to be an encouraging candidate to treat cognitive deficits and depression after severe sepsis.

Mdivi-1 attenuates lipopolysaccharide-induced acute lung injury by inhibiting MAPKs, oxidative stress and apoptosis.

Sepsis is among the most devastating events in intensive care units. As a complication of sepsis, acute lung injury (ALI) is common and highly associated with poor outcome. The present study demonstrated that abnormal mitochondrial dynamics play a pivotal role in lipopolysaccharide (LPS)-induced ALI. Inhibiting the mitochondrial fission with the specific inhibitor-1 (Mdivi-1) ameliorated ALI as assessed by hematoxylin and eosin (H&E) staining and wet/dry ratio. Furthermore, Mdivi-1 reduced mitogen-activated protein kinases (MAPKs) activation, oxidative stress and apoptosis in the lungs. Plasma pro-inflammation cytokines were also reduced significantly in Mdivi-1-treated mice. In vitro study revealed that Mdivi-1 protected the macrophages from LPS-induced MAPKs activation, oxidative stress and cell apoptosis. Mdivi-1 also inhibited the release of pro-inflammatory cytokines. Morphological analysis showed that Mdivi-1 rescued the macrophages from LPS-induced mitochondrial fragmentation. Moreover, LPS treatment induced significant phosphorylation of Drp1 at Ser616, dephosphorylation at Ser637 and translocation of Drp1 from the cytoplasm to mitochondria, while Mdivi-1 inhibited those effects. Thus, modification of fission to rebuild mitochondrial homeostasis may offer an innovative opportunity for developing therapeutic strategies against ALI.

Shorter Telomere Length in Peripheral Blood Leukocytes Is Associated with Post-Traumatic Chronic Osteomyelitis.

Background: This study investigated the association between post-traumatic chronic osteomyelitis (COM) and peripheral leukocyte telomere length (PLTL) and explored factors associated with PLTL in COM. Methods: A total of 56 patients with post-traumatic COM of the extremity and 62 healthy control subjects were recruited. The PLTL was measured by real-time PCR. Binary logistic regression analysis was used to identify factors in correlation with telomere length. Sex, age, white blood cell (WBC) count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and infection duration were included as independent variables in the logistic regression model. Results: Post-traumatic COM patients had significantly shorter PLTLs (5.39 ± 0.40) than healthy control subjects (5.69 ± 0.46; p < 0.001). Binary logistic regression analysis showed that PLTL had a statistically significant association with age (B = -0.072; p = 0.013) and CRP (B = -0.061; p = 0.033). The logistic regression model was statistically significant and explained 31.4% (Nagelkerke R2) of the change in telomere length and correctly classified 69.6% of the cases. Conclusions: Patients with post-traumatic COM have shorter PLTLs than healthy subjects. The PLTL erosion of post-traumatic COM was partially explained by age and CRP.

SS-31 reduces inflammation and oxidative stress through the inhibition of Fis1 expression in lipopolysaccharide-stimulated microglia.

SS-31 is a kind of mitochondrion-targeted peptide. Recent studies indicated significant neuroprotective effects of SS-31. In this study, we investigated that SS-31 protected the murine cultured microglial cells (BV-2) against lipopolysaccharide (LPS)-induced inflammation and oxidative stress through stabilizing mitochondrial morphology. The morphological study showed that SS-31 preserved LPS-induced mitochondrial ultrastructure by reducing the fission protein 1 (Fis1) expression. Flow cytometry and Western blot verified that SS-31 defended the BV-2 cells against LPS-stimulated inflammation and oxidative stress via suppressing Fis1. To sum up, our study represents that SS-31 preserves BV-2 cells from LPS-stimulated inflammation and oxidative stress by down-regulating the Fis1 expression.

Mechanical Stretch Promotes the Osteogenic Differentiation of Bone Mesenchymal Stem Cells Induced by Erythropoietin.

INTRODUCTION: The effects of erythropoietin (EPO) on the behaviors of bone marrow mesenchymal stem cells (BMSCs) subjected to mechanical stretch remain unclear. This study was therefore aimed at establishing the dose-response effect of EPO stimulation on rat BMSCs and investigating the effects of mechanical stretch combined with EPO on the proliferation and osteogenic differentiation of BMSCs. MATERIAL AND METHODS: The proliferation and osteogenic differentiation of rat BMSCs were examined and compared using EPO with different concentrations. Thereafter, BMSCs were subjected to 10% elongation using a Flexcell strain unit, combined with 20 IU/ml EPO. The proliferation of BMSCs was detected by Cell Counting Kit-8, colony formation assay, and cell cycle assay; meanwhile, the mRNA expression levels of Ets-1, C-myc, Ccnd1, and C-fos were detected by reverse transcription and real-time quantitative PCR (qPCR). The osteogenic differentiation of BMSCs was detected by alkaline phosphatase (ALP) staining, and the mRNA expression levels of ALP, OCN, COL, and Runx2 were detected by qPCR. The role of the extracellular signal-regulated kinases 1/2 (ERK1/2) in the osteogenesis of BMSCs stimulated by mechanical stretch combined with 20 IU/ml EPO was examined by Western blot. RESULTS: Our results showed that effects of EPO on BMSCs included a dose-response relationship, with the 20 IU/ml EPO yielding the largest. Mechanical stretch combined with 20 IU/ml EPO promoted proliferation and osteogenic differentiation of BMSCs. The increase in ALP, mineral deposition, and osteoblastic genes induced by the mechanical stretch-EPO combination was inhibited by U0126, an ERK1/2 inhibitor. CONCLUSION: EPO was able to promote the proliferation and osteogenic differentiation of BMSCs, and these effects were enhanced when combined with mechanical stretch. The underlying mechanism may be related to the activation of the ERK1/2 signaling pathway.

Serum glial fibrillary acidic protein and ubiquitin C-terminal hydrolase-L1 for diagnosis of sepsis-associated encephalopathy and outcome prognostication.

PURPOSE: We investigated the role of serum Glial Fibrillary Acidic Protein (GFAP) and Ubiquitin C-Terminal Hydrolase-L1 (UCH-L1) in diagnosis of sepsis-associated encephalopathy(SAE), predicting prognosis and long-term quality of life with patients of sepsis. MATERIALS AND METHODS: This is a prospective single center study entailed 105 patients whosuffered from sepsis from Jan 2015 to Aug 2016. Serum concentrations of GFAP and UCH-L1 for diagnosis of SAE and predicting prognosis and long-term quality of life with patients of sepsis were analyzed. RESULTS: The serum concentrations of GFAP and UCH-L1 were higher in SAE group than in no-SAE group (p < .001). GFAP and UCH-L1 produced an AUC of 0.824 and 0.812 respectively for diagnosis of SAE with optimal cut-off values 0.532 ng/ml and 7.72 ng/ml respectively. The optimal cut-off values of GFAP and UCH-L1 to distinguish patients with survivors from non-survivors were 0.536 ng/ml and 8.06 ng/ml with an area under the curve of 0.773 and 0.746. Patients with a higher GFAP levels had worse long-term usual activities and patients with a higher UCH-L1 levels had more long-term pain (P = .026). CONCLUSIONS: Serum concentrations GFAP and UCH-L1 early elevated and associated with sepsis-associated encephalopathy, poor prognosis and quality of life.

Characterization of Sepsis and Sepsis-Associated Encephalopathy.

BACKGROUND: Sepsis and sepsis-associated encephalopathy (SAE) are common intensive care unit (ICU) diseases; the morbidity and mortality are high. The present study analyzed the sensitivity of different diagnostic criteria of sepsis 1.0 and 3.0, epidemiological characteristics of sepsis and SAE, and explored its risk factors for death, short-term, and long-term prognosis. METHODS: The retrospective study included patients in ICU from January 2015 to June 2016. After excluding 58 patients, 175 were assigned to either an SAE or a non-SAE group (patients with sepsis but no encephalopathy). The sensitivity of the diagnostic criteria was compared between sepsis 1.0 and 3.0, respectively. Between-group differences in baseline data, Acute Physiology and Chronic Health Evaluation II score (APACHE II score), Sequential Organ Failure Assessment score (SOFA score), etiological data, biochemical indicators, and 28-day and 180-day mortality rates were analyzed. Survival outcomes and long-term prognosis were observed, and risk factors for death were analyzed through 180-day follow-up. RESULTS: The sensitivity did not differ significantly between the diagnostic criteria of sepsis 1.0 and 3.0 (P = .286). The 42.3% incidence of SAE presented a significantly high APACHE II and SOFA scores as well as 28-day mortality and 180-day mortality (all P < .001). The incidence of death was 37.1%. The multivariate stepwise regression analysis demonstrated that the risk of death in SAE group was significantly higher than the non-SAE group (P < .001). Sepsis-associated encephalopathy is a risk factor for sepsis-related death (relative risk [RR] = 2.868; 95% confidence interval: 1.730-4.754; P < .001). Although males showed a significantly high rate of 28-day and 180-day mortality (P = .035 and .045), it was not an independent risk factor for sepsis-related death (P = .072). The long-term prognosis of patients with sepsis was poor with decreased quality of life. No significant difference was observed in prognosis between the SAE and non-SAE groups (P > .05). CONCLUSION: Both diagnostic criteria cause misdiagnosis, and the sensitivity did not differ significantly. The incidence of SAE was high, and 28-day and 180-day mortality rates were significantly higher than those without SAE. Sepsis-associated encephalopathy is a risk factor for poor outcome. The overall long-term prognosis of patients with sepsis was poor, and the quality of life decreased.

Intensity-dependent effect of treadmill running on rat Achilles tendon.

It is understood that mechanical loading may affect tendon properties. However, how different mechanical loading conditions may affect tendons remains unknown. The present study aimed to investigate the effect of treadmill running at various intensities on rat Achilles tendon. A total of 18 male Wistar rats were randomly assigned to one of three groups: Control (CON), medium-intensity running (MIR), and high-intensity running (HIR). Following 8 weeks of treadmill running protocols, all Achilles tendons were harvested for histological observation and gene expression analysis. Significant morphological changes were observed with regular and large diameter collagen fibrils in the MIR group, whereas irregular and small diameter collagen fibrils were observed in the HIR group. Collagen type I was significantly upregulated in the MIR group compared with the CON group, and downregulated in the HIR group compared with the CON or MIR groups (P<0.05). However, collagen type III was significantly upregulated in the HIR group in comparison with the CON or MIR groups (P<0.05). Furthermore, the expression of matrix metallopeptidase-13 was significantly increased in the MIR and HIR groups compared with the CON group (P<0.05). The expression of tissue inhibitor of metalloproteinases-1 was increased in the MIR group compared with the CON group, but decreased in the HIR group compared with the CON and MIR groups (P<0.05). Additionally, decorin expression was significantly higher in the MIR group compared with the CON group, and significantly decreased in the HIR group compared with the CON or MIR groups (P<0.05). A converse pattern of changes in biglycan expression was identified among the three groups. Aggrecan expression was significantly higher in the HIR group compared with the CON or MIR groups (P<0.05). These findings indicated that moderate exercise may induce increased collagen synthesis and organize regular and large collagen fibers, thus benefiting the Achilles tendon. However, overuse during exercise may result in collagen degradation and disturbance, which predisposes individuals to injury.

Response of decorin to different intensity treadmill running.

Decorin is widely understood to affect collagen fibrillogenesis. However, little is understood about its response to various mechanical loading conditions. In the present study, 36 Wistar rats were randomly divided into control (CON), moderate treadmill running (MTR) and strenuous treadmill running (STR) groups. Animals in the MTR and STR groups were subjected to a 4­ or 8­week treadmill running protocol. Subsequently, all Achilles tendons were harvested to perform histological and biochemical analyses. Decorin expression was markedly increased in the MTR group compared with the CON group at 4 and 8 weeks. Conversely, decorin expression was markedly decreased in the STR group compared with the CON and MTR group at 4 and 8 weeks. Furthermore, between the two time points, decorin expression levels were significantly increased in the MTR group, whereas they were markedly decreased in the STR group. These results suggested that MTR exercise may induce increased decorin expression via a balance of MMP­2 and TIMP­2, improving tendon structure and function. However, STR exercise may result in degradation of decorin due to an imbalance of MMP­2 and TIMP­2, with a bias to MMP­2, resulting in a predisposition to tendinopathy.