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To determine the prevalence of inapparent infection with severe acute respiratory syndrome (SARS) among healthcare workers, we performed a serosurvey to test for immunoglobulin (Ig) G antibodies to the SARS [...]

Abstract Background Despite the use of a series of preventive measures, a high incidence of severe acute respiratory syndrome (SARS) was observed among health care workers (HCWs) during the SARS epidemic. This study aimed to determine which preventive measures may have been effective in protecting HCWs from infection, and which were not effective. Methods A retrospective study was performed among 758 'frontline' health care workers who cared for SARS patients at the Second Affiliated Hospital and the Third Affiliated Hospital of Sun Yat-sen University. The HCWs with IgG against SARS and those without IgG against SARS were respectively defined as the "case group" and the "control group", and logistic regression was conducted to explore the risk factors for SARS infection in HCWs. Results After adjusting for age, gender, marital status, educational level, professional title, and the department in which an individual worked, the results of a multivariate logistic regression analysis indicated that incidence of SARS among HCWs was significantly and positively associated with: performing tracheal intubations for SARS patients, methods used for air ventilation in wards, avoiding face-to-face interaction with SARS patients, the number of pairs of gloves worn by HCWs, and caring for serious SARS cases. Conclusion Some measures, particularly good air ventilation in SARS wards, may be effective in minimizing or preventing SARS transmission among HCWs in hospitals.

Background Neuroactive steroids represent promising candidates for the treatment of neurological disorders. Our previous studies identified an endogenous steroid cholestane-3 β, 5 α, 6 β-triol (Triol) as a novel neuroprotectant. Aim We aimed to identify a potent candidate for stroke treatment through a screening of Triol analogs. Methods Hypoxia- and glutamate-induced neuronal injury models in vitro, middle cerebral artery occlusion ( MCAO)-induced cerebral ischemia model in vivo, fluorescein diacetate ( FDA) for alive and propidium iodide ( PI) for dead staining, LDH assay, and calcium imaging techniques were used. Results 24-keto-cholest-5-en-3 β, 19-diol (Diol) showed the most potent neuroprotective effect among the screened structurally related compounds. FDA and PI staining showed that Diol concentration dependently increased the survival rate of cerebellar granule neurons ( CGNs) challenged with glutamate or hypoxia, with an effective threshold concentration of 2.5 μM. Consistently, the quantitative LDH release assay showed the same concentration-dependent protection in both models. Diol, at 10 μM, potently decreased glutamate- and hypoxia-induced LDH release from 51.6 to 18.2% and 62.1 to 21.7%, respectively, which values are close to the normal LDH release (~16-18%). Moreover, we found Diol effectively decreased MCAO-induced infarction volume in mice from ~23% to 7%, at a dose of 6 mg/kg. We further explored the underlying mechanism and found that Diol attenuated NMDA-induced intracellular calcium ([Ca2+]i) increase in cortical neurons, suggesting a negative modulatory effect on NMDA receptor. Conclusion Taken together, we identified Diol as a potent neuroprotectant. It may represent a novel and promising neuroprotectant for stroke intervention. [ABSTRACT FROM AUTHOR]

AbstractAim:To evaluate the effects of the fibrinolytic enzyme FIIa from Agkistrodon acutus venom on acute pulmonary thromboembolism (APT) in animal models.Methods:Both rabbit and dog APT models were used. For the rabbit APT model, the thrombi weight before and after administration was measured. Central venous pressure (CVP) and mean arterial pressure (MAP) were measured before and 15, 30, 60, and 120 min after the injection of the blood clot. Partial thromboplastin time (APTT), prothrombin time (PT), platelet count, and fibrinogen concentration were measured using auto analyzers. Plasminogen activity was measured based on chromogenic substrates. In the dog APT model, pulmonary blood flow was recorded using pulmonary angiography.Results:Intravenous administration of FIIa (0.1-5.0 mg/kg) improved the APT-induced hemodynamic derangements and reduced thrombi weight. The angiography evidence also showed that the pulmonary emboli had almost disappeared after FIIa infusion. FIIa (0.1, 0.5, or 1.0 mg/kg) did not impair the coagulation pathways, although very high doses of FIIa (5.0 mg/kg) could stimulate the production of plasminogen and result in impairment of the pathways.Conclusion:FIIa could effectively protect against APT via degradation of thrombi with less activation of plasminogen, and may provide a novel fibrinolytic enzyme for targeting the main pathological processes of the disease. [ABSTRACT FROM AUTHOR]

A novel fibrinolytic enzyme, FIIa, was isolated from Agkistrodon acutus venom, which can degrade fibrin/fibrinogen and dissolve thrombus without activating plasminogen or influencing the activities of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type-1 (PAI-1). In this study, we evaluated the effect of FIIa on lipopolysaccharide (LPS)-induced experimental disseminated intravascular coagulation (DIC) in rabbits, through the continuous infusion of 100-μg/kg/h LPS for a period of 6 h. Seven groups were established: LPS control, FIIa (0.1, 0.3, and 0.6 mg/kg/h, respectively), heparin control (100 IU/kg/h), heparin + FIIa (heparin 100 IU/kg/h associated with FIIa 0.3 mg/kg/h), and a saline control group. A continuous injection of LPS induced a gradual impairment in hemostatic parameters, kidney fibrin deposition, and a high mortality rate. The intravenous administration of FIIa improved the concentration of fibrinogen, the activities of protein C, plasminogen, t-PA, antithrombin III (ATIII), and PAI-1. Kidney fibrin deposition and the mortality also decreased. In the in vitro experiments, FIIa can degrade fibrin/fibrinogen and high-dose FIIa enhanced the activity of protein C. These findings suggest that the effects of FIIa on LPS-induced DIC were from fibrinogen degradation and enhanced protein C activity. The simultaneous administration of FIIa and heparin further improved all the hemostatic parameters, including decreased kidney fibrin deposition, and none of the rabbits died within 24 h, which indicates that the effects were mediated by degradation of fibrin/fibrinogen together with thrombin inhibition. We conclude that FIIa may be useful in the treatment of DIC. [Copyright &y& Elsevier]

Following the publication of our paper (Zhang et al., 2020), it has come to our attention that we erroneously listed two funding sources unrelated to this study in the "ACKNOWLEDGEMENTS" section. Hereby, we wish to update the "ACKNOWLEDGEMENTS" section as a correction.

Hypobaric hypoxia (HH) exposure can cause serious brain injury as well as life-threatening cerebral edema in severe cases. Previous studies on the mechanisms of HH-induced brain injury have been conducted primarily using non-primate animal models that are genetically distant to humans, thus hindering the development of disease treatment. Here, we report that cynomolgus monkeys ( Macaca fascicularis ) exposed to acute HH developed human-like HH syndrome involving severe brain injury and abnormal behavior. Transcriptome profiling of white blood cells and brain tissue from monkeys exposed to increasing altitude revealed the central role of the HIF-1 and other novel signaling pathways, such as the vitamin D receptor (VDR) signaling pathway, in co-regulating HH-induced inflammation processes. We also observed profound transcriptomic alterations in brains after exposure to acute HH, including the activation of angiogenesis and impairment of aerobic respiration and protein folding processes, which likely underlie the pathological effects of HH-induced brain injury. Administration of progesterone (PROG) and steroid neuroprotectant 5α-androst-3β,5,6β-triol (TRIOL) significantly attenuated brain injuries and rescued the transcriptomic changes induced by acute HH. Functional investigation of the affected genes suggested that these two neuroprotectants protect the brain by targeting different pathways, with PROG enhancing erythropoiesis and TRIOL suppressing glutamate-induced excitotoxicity. Thus, this study advances our understanding of the pathology induced by acute HH and provides potential compounds for the development of neuroprotectant drugs for therapeutic treatment.

Aim: To investigate whether aspirin is able to augment gemcitabine-induced cytotoxicity in human pancreatic cancer cells., Methods: Two gemcitabine-insensitive human pancreatic cancer cell lines, PANC-1 and Capan-1, were used. Cells were treated with either aspirin or gemcitabine alone or both of them. Cell growth and apoptosis were determined by MTT assay, Annexin V or Hoechest 33258 staining. Cell cycle distribution was examined by flow cytometry. Western blot with specific phosphorylated protein antibodies was used to detect the activation of protein kinase. RT-PCR and Western blot were applied to assess the transcription and protein level for cyclin D1 and Bcl-2., Results: Aspirin alone significantly inhibits the proliferation of PANC-1 cells by causing cell cycle arrest at G(1) phase. Aspirin potentiates the anti-survival effect of gemcitabine as well as its pro-apoptotic effect in PANC-1 cells, although aspirin per se does not trigger apoptosis. Aspirin inhibits GSK-3beta activation and suppresses the expression of its downstream gene products (cyclin D1 and Bcl-2), which are implicated in proliferation, survival and chemoresistance of pancreatic cancer. The effects of aspirin on Capan-1, were similar to that on PANC-1., Conclusion: Our results suggest that aspirin inhibits the proliferation of gemcitabine-resistant pancreatic cancer cells and augments the antisurvival effect of gemcitabine, probably by suppressing the activity of GSK-3beta and its downstream gene products.

Aim: To analyze YZ-2, a novel protein associated with cerebral ischemia and prepares its polyclonal antibody., Methods: According to the bioinformatics analysis and prediction of the possible high structure, hydrophilicity and antigenicity of YZ-2, a 22-amino acid residue partial peptide of YZ-2 was synthesized. The synthesized peptide was then used to immunize. And the properties of anti-YZ2 were analyzed by ELISA and Western blot., Results: The hydrophilicity and antigenicity were predicted by methods of bioinformatics. The polyclonal antibody of YZ-2 was successfully obtained and its specificity and sensitivity were conformed by ELISA and Western blot., Conclusion: By the bioinformatics analysis and prediction, the hydrophilicity and antigenicity of YZ2 were analyzed. The antibody of YZ-2 was successfully obtained.

Aim: To explore the possibility that expressions of different heat shock proteins (HSPs) are specifically involved in the protection of thermal preconditioning against apoptosis of cerebellar granule neurons (CGNs) induced by repolarization., Methods: Western blotting was used to detect expressions of HSP27, HSP70, and HSP90 induced by thermal preconditioning (TP) in CGNs; reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the expression level of HSP70 mRNA; apoptosis of CGNs was induced by switching culture medium containing KCl 25 mmol/L to one containing KCl 5 mmol/L., Results: No expression of HSP27 in cerebellar granule neurons was observed with TP at 44 degree. Expression of HSP90 was obvious in CGNs both without and with TP at 44 degree for different periods. Expression of HSP70 protein in CGNs was lower with TP at 44 degree for 5 min, but it increased gradually after the period was prolonged to 30, 60, or 90 min. HSP70 mRNA was detected after TP 44 degree for 30, 60, and 90 min and increased gradually with time. HSP70 antisense oligodeoxynucleotides 10 micromol/L for 72 h inhibited the protective effects of TP at 44 degree on apoptosis of CGNs induced by repolarization., Conclusion: HSP70 is involved in protective effects of thermal preconditioning on apoptosis in cerebellar granule neurons induced by repolarization.

Aim: To study the local hemorrhagic activity of a fibrinolytic enzyme (FII(a)) from Agkistrodon acutus venom and its mechanism., Methods: The local hemorrhagic activity was determined by subcutaneous injection on the back of mouse. The effects of FIIa on factor X, prothrombin, gelatin, and collagen were visualized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Platelet aggregation assays were performed in rat platelet-rich plasma (PRP). Human umbilical vein endothelial cells (HUVEC) were cultured and passaged in complete M199 medium. Cell viability and nuclear morphology change were determined by fluorescein diacetate (FDA) staining and Hoechst 33258 staining, respectively., Results: The minimum hemorrhagic dose (MHD) of FIIa was 89 microg. In vitro, FII(a) (0.25 g/L) degraded factor X, prothrombin, collagen, and gelatin, and dose-dependently (0.25, 0.50, 0.75, and 1.00 g/L) inhibited the platelet aggregation induced by ADP in rat PRP. When HUVEC in culture treated with FII(a), HUVEC showed detachment in a dose-dependent manner, but no apoptosis sign was observed., Conclusion: FIIa had local hemorrhagic activity, and the mechanism was related to the degradation of factor X, prothrombin, gelatin, and collagen, the inhibition of ADP-induced platelet aggregation, and inducement of HUVEC detachment.

Aim: To investigate possible intracellular signal molecules involved in diphenylhydantoin (DPH)-mediated apoptosis of cerebellar granule neurons (CGN) and explore possible molecular mechanisms of neurotoxicity of DPH., Methods: Fluorescein diacetate (FDA) stain, hochest 33258 stain, and agar gel electrophoresis were used to test morphological and biological characters of primary CGN and cortical neurons (CN) in the presence or absence of 100 micromol/L DPH; Western blot and RT-PCR were employed to further investigate apoptotic/survival signal moleculars involved in the neuronal apoptotic signal transdution., Results: DPH 100 micromol/L induced a typical apoptosis of CGN but had no toxicity on CN. Cerebellar granule neural apoptosis induced by 100 micromol/L DPH was significantly inhibited by pre-treatment with SB203580 (10 micromol/L) or CEP-11004 (1 micromol/L) for 1 h. DPH markedly upregulated the levels of phospho-c-Jun (active c-Jun), total c-Jun protein and c-jun mRNA in CGN. The levels of phospho-c-Jun dramatically elevated by DPH at 8 h were significantly inhibited by SB203580 (10 micromol/L) or CEP-11004 (1 micromol/L). Moreover, the activities of p44/42 (ERK1/ERK2), other members of MAP kinases and generally believed to be important survival effetors in CGN, were markedly suppressed. However, the activities of both JNK and p38 were little affected in the process of apoptosis of CGN induced by 100 micromol/L DPH., Conclusion: The selective toxicity of DPH on CGN is likely due to its ability to induce apoptosis of CGN, it is a process involved activation of c-Jun and suppression of the activity of p44/42.

Low dose radiation induces apoptosis and Bcl-2 can inhibit apoptosis induced by a variety of stimuli. The effects and possible mechanisms of Bcl-2 on 4 Gy X-ray-induced apoptosis in Bcl-2 transfected and untransfected cells were studied. The data present here suggested that overexpression of Bcl-2 significantly inhibited X-ray-induced apoptosis in CHO cells within 72 h. Further investigation demonstrated that Bcl-2 prevented the loss of mitochondrial membrane potential (deltapsim) induced by X-ray irradiation. It appears that overexpression of Bcl-2 blocked the ionizing radiation-induced apoptosis. The maintenance of deltapsim plays an important role in the protective mechanism of Bcl-2 on ionizing radiation-induced apoptosis.