Bioinspired Heteromultivalent Chitosan-α-Fe2O3/Gadofullerene Hybrid Composite for Enhanced Antibiotic-Resistant Bacterial Pneumonia.

Herein, we have designed and developed a heteromultivalent chitosan base α-Fe2O3/Gadofullerene (GdF) hybrid composite through a simple chemical precipitation method. Unlike other methods, the addition of external stabilizing agents to generate GdF nanoparticles (NPs) was not necessary herein. The prepared chitosan-α-Fe2O3/GdF hybrid nanocomposites were characterized using UV, FT-IR, XRD and morphological microscopic analyses. The results showed that α-Fe2O3 and GdF hybrid nanocomposites were successfully grown on the surface of chitosan. The FT-IR vibration peaks showed the formation of Fe2O3 NPs, and the vibration peak for Fe-O was 568 cm-1. The broad absorption peak observed in the range of 250-350 nm and a sharp absorption peak at 219 nm represents the UV absorption of the synthesized hybrid composites. XRD pattern showed sharp peaks of crystallinity and purity of α-Fe2O3 nanoparticles. Finally, the synthesized chitosan-α-Fe2O3/GdF hybrid composites were screened for their antibacterial resistance against the Escherichia coli, Pseudomonas aeruginosa, Bacilus subtilis, and Staphylococcus aereus. In addition, in vitro biocompatibility results exhibited that developed hybrid samples have provided high cell compatibility with fibroblast (L929) cell line. The in vivo bio inspired nanotherapeutics have the potential action to effective inhibition ability on antibiotic-resistant P. aeruginosa, which has been main factor of inducing pneumonia. In conclusion, we expect biomimicking systems combined with the effective antibacterial agent could be the suitable next generation therapeutic potential factors for prevention and treatment of antibiotic-resistant pneumonia.

The Role of Potassium Channels in Chronic Stress-Induced Brain Injury.

Chronic stress-induced brain injury (CSBI) is the organic damage of brain tissue caused by long-term psychological and environmental stress. However, there is no effective drug for the treatment of CSBI. The present study aimed to investigate possible mechanisms of CSBI and to explore related therapeutic targets. A rat model of CSBI was established by combining chronic restraint and cold water immersion. Our CSBI model was validated via Nissl staining, Western blotting, and behavioral tests. RNA sequencing (RNA-seq) was used to identify differentially expressed genes (DEGs) within brain tissue during CSBI. Both Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses were performed to determine signaling pathways associated with CSBI-induced DEGs. Agonists/antagonists were used to validate the pharmacodynamics of potential therapeutic targets. A combination of chronic restraint and cold water immersion successfully induced a rat model of CSBI, as indicated by various markers of brain injury and cell apoptosis that were verified via Nissl staining, Western blotting, and behavioral tests. RNA-seq analysis identified 1131 DEGs in CSBI rats. Of these DEGs, 553 genes were up-regulated and 778 genes were down-regulated. GO and KEGG pathway analyses revealed that significant DEGs were predominantly related to membrane-bound ion channels, among which the potassium channel function was found to be significantly affected. Pharmacological experiments revealed that retigabine, a voltage-gated potassium channel opener, demonstrated a protective effect in CSBI rats. Taken together, our findings suggest that potassium channel function is disrupted in CSBI, and that potassium channel regulators may function as anti-CSBI drugs.

Efficacy and safety of adjunctive corticosteroids therapy for patients with severe community-acquired pneumonia: A systematic review and meta-analysis.

BACKGROUND: The systemic use of corticosteroids for patients in severe community-acquired pneumonia (CAP) remains disputed in clinical practice. We undertook a systematic review and meta-analysis to assess the efficacy and safety of corticosteroids in patients with severe CAP. METHODS: We searched MEDLINE (1946 to June 2018), EMBASE (1966 to June 2018), and the Cochrane Library database for randomized controlled trials (RCTs) conducted for severe CAP. The endpoints of the study included total mortality, length of intensive care unit (ICU) stay and mechanical ventilation. RESULTS: Nine trials which contained 914 patients were included for final meta-analysis. Of the 488 patients in the corticosteroid group, there were 37 deaths (7.58%) and 56 deaths occurred in 426 patients in the control group (13.1%). Corticosteroid therapy was associated with a lower rate of all-cause mortality compared to control (odd ratio [OR] 0.63, 95% confidence interval [CI] 0.42-0.95, P = .03). Subgroup analysis was conducted to show that the drug type modified the effect of steroids for mortality rate: prednisolone or methylprednisolone therapy (OR 0.37, 95% CI 0.19-0.72) reduced total mortality, whereas hydrocortisone use did not (OR 0.90, 95% CI 0.54-1.49). We found the length of ICU stay was significantly shorter in the steroid group compared to control (MD -2.52 days, 95% CI -4.88 to -0.15; P = .04). And there was a reduction trend in the need for mechanical ventilation in corticosteroid group (OR 0.53, 95% CI 0.28-1.02; P = .06). There was no trend towards more adverse events in the corticosteroid arm compared to control (OR 0.92, 95% CI 0.58-1.47; P = .74). CONCLUSION: Overall, adjunctive systemic corticosteroids therapy was effective and safe for patients with severe CAP. In addition, the effects of mortality may differ according to the type of corticosteroids.

Cytotoxic and Antitumor Effects of Curzerene from Curcuma longa.

Curzerene is a sesquiterpene and component used in oriental medicine. It was originally isolated from the traditional Chinese herbal medicine Curcuma rhizomes. In this study, anticancer activity of curzerene was examined in both in vitro and in vivo models. The result of the MTT assay showed that curzerene exhibited antiproliferative effects in SPC-A1 human lung adenocarcinoma cells in a time-dependent and dose-dependent manner. The anticancer IC50s were 403.8, 154.8, and 47.0 µM for 24, 48, and 72 hours, respectively. The flow cytometry analysis indicated curzerene arrested the cells in the G2/M cell cycle and promoted or induced apoptosis of SPC-A1 cells. The percentage of cells arrested in the G2/M phase increased from 9.26 % in the control group cells to 17.57 % in the cells treated with the highest dose (100 µM) of curzerene. Western blot and RT-PCR analysis demonstrated that curzerene induced the downregulation of GSTA1 protein and mRNA expressions in SPC-A1 cells. Tumor growth was significantly inhibited in SPC-A1 cell-bearing nude mice by using curzerene (135 mg/kg daily), meanwhile, curzerene did not significantly affect body mass and the organs of the mice, which may indicate that curzerene has limited toxicity and side effects in vivo. In conclusion, curzerene could inhibit the proliferation of SPC-A1 human lung adenocarcinoma cells line in both in vitro and in vivo models. Focusing on its relationship with GSTA1, curzerene could induce the downregulation of GSTA1 protein and mRNA expressions in SPC-A1 cells. Curzerene might be used as an anti-lung adenocarcinoma drug candidate compound for further development.

Curcumol induces apoptosis in SPC-A-1 human lung adenocarcinoma cells and displays anti-neoplastic effects in tumor bearing mice.

Curcumol is a sesquiterpene originally isolated from curcuma rhizomes, a component of herbal remedies commonly used in oriental medicine. Its beneficial pharmacological activities have attract significant interest recently. In this study, anti-cancer activity of curcumol was examined with both in vitro and in vivo models. It was found that curcumol exhibited time- and concentration-dependent anti-proliferative effects in SPC-A-1 human lung adenocarcinoma cells with cell cycle arrest in the G0/G1 phase while apoptosis-induction was also confirmed with flow cytometry and morphological analyses. Interestingly, curcumol did not display growth inhibition in MRC-5 human embryonic lung fibroblasts, suggesting the anti-proliferative effects of curcumol were specific to cancer cells. Anti-neoplastic effects of curcumol were also confirmed in tumor bearing mice. Curcumol (60 mg/kg daily) significantly reduced tumor size without causing notable toxicity. In conclusion, curcumol appears a favorable anti-cancer candidate for further development.

[Application of high-frequency electrocautery combined with high pressure balloon expansion in treatment of benign airway obstruction].

OBJECTIVE: To study the value of high-frequency electrocautery combined with high-pressure balloon expansion in the treatment of benign airway obstruction. METHODS: Twelve patients with complete airway obstruction received treatment with high-frequency electrocautery and high-pressure balloon expansion, and 6 months of follow-up was performed. RESULTS: After the initial treatment, the rate of airway obstruction relief exceeded 50% in 8 patients, who showed lung recruitment and an increased dyspnea index, suggesting total effectiveness; one patient showed mild improvement with airway stenosis relief by less than 50% (the upper-left lobe remained obstructed). Stents were implanted eventually in 7 patients for airway maintenance. Two patients showed relief of the airway obstruction by over 50% after the initial treatment, but lung recruitment or dyspnea relief failed to be achieved, suggesting non-response to the treatment. The airway failed to be found in 1 case (who received 5 previous operations of ablation and dilatation), which was considered a non-response case. CONCLUSION: High-frequency electrocautery combined with high pressure balloon expansion is clinically effective with few complications in some cases of benign complete airway stenosis. The possibility of airway stenosis and even obstruction should be considered in patients with tuberculosis during the treatment.

[A retrospective cohort study of the influence of time of hospital-acquired pneumonia onset on pathogen constitution].

OBJECTIVE: To study the influence of duration of hospitalization on etiologic agent and antibiotic-resistance of hospital-acquired pneumonia (HAP). METHODS: Cases of HAP were patients hospitalized in Fudan University Zhongshan Hospital, Ruijin Hospital, Beijing Hospital, Zhongshan University Affiliated Third Hospital, Guangzhou Medical College Affiliated Hospital and Guangdong People's Hospital. These patients were hospitalized from January 2001 to December 2003, and the diagnosis of HAP was made based on positive respiratory specimen cultures. Clinical data including time of HAP onset, severity of illness, risk factors, isolated bacteria and antimicrobial susceptibility were collected and analyzed. Statistical analysis was performed with the SPSS 12.0 software. RESULTS: A total of 562 cases of HAP were recruited, including 136 cases of early-onset pneumonia (time of onset < or = 5 d), 326 cases of middle-onset pneumonia (time of onset 6 - 14 d) and 100 cases of late-onset pneumonia (time of onset > or = 15 d). The rate of prior antibiotic use increased from 68.4% in the early-onset group to 88.0% in the late-onset group (P = 0.002); ICU admission increased from 29.4% to 46.0% (P = 0.03), and immunosuppression increased from 1.5% to 15% (P = 0.001). A total of 918 strains of bacteria were isolated, the most common pathogens being Pseudomonas aeruginosa (18.6%), Staphylococcus aureus (16.1%), Acinetobacter spp (16.1%), Klebsiella spp (14.4%) and Enterobacter spp (8.8%). Early-onset HAP were more commonly caused by Klebstella (18.3%), while the main etiologic agents for late-onset HAP were Pseudomonas aeruginosa (24.2%) and Methicillin-resistant Staphylococcus aureus (19.3%). The rates of pneumonia caused by Haemophilus and Streptococcus were 4.3% and 2.4% respectively in the early-onset cases, but none was found in late-onset cases. The antibacterial activity of ceftriaxone was influenced by duration of hospitalization, risk factors and severity of the disease. In less severe early-onset cases without risk factors, the sensitivity of ceftriaxone was 80%. But in severe late-onset cases, it was only 50%. CONCLUSIONS: There was significant difference in the pathogen constitution and antibiotic-resistance among early-onset, middle-onset and late-onset cases of HAP. The sensitivity of ceftriaxone was high in less severe early-onset cases without risk factors.