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Background Arsenic exposure is a common and important environmental and occupational hazardous factor in China, and arsenic-induced insulin resistance (IR) has attracted widespread attention as a negative health outcome to the population. Objective To explore part of the mechanism of hepatic IR induced by arsenic exposure based on the peroxisome proliferators-activated receptors γ (PPARγ)/ glucose transporter 4 (GLUT4) pathway, and to investigate potential effects of Ginkgo biloba extract (GBE) on hepatic IR induced by arsenic exposure and associated mechanism of action. Methods The target of drug action was predicted by network pharmacology and verified by in vivo and in vitro experiments. In vivo experiments: 48 SPF C57BL/6J male mice were divided into 4 groups, including control group, 50 mg·L−1 NaAsO2 model group (NaAsO2), 50 mg·L−1 NaAsO2+10 mg·kg−1 GBE intervene group (NaAsO2+GBE), and 10 mg·kg−1 GBE group (GBE), 12 mice in each group. The animals were given free access to purified water containing 50 mg·L−1 NaAsO2, or given intraperitoneal injection of normal saline containing 10 mg·kg−1 GBE once per week. After 6 months of exposure, blood glucose detection, intraperitoneal glucose tolerance test (IPGTT), and insulin tolerance test (ITT) were performed. Serum and liver tissues were collected after the mice were neutralized, liver histopathological sections were obtained, serum insulin levels, liver tissue glycogen content, glucose content were detected by enzyme linked immunosorbent assay (ELISA), and the expression of PPARγ and GLUT4 proteins was detected by Western blot (WB). In vitro experiments: HepG2 cells were divided into 4 groups, including control group, 8 μmol·L−1 NaAsO2 group (NaAsO2), 8 μmol·L−1 NaAsO2 + 200 mg·L−1 GBE intervene group (NaAsO2+GBE), and 200 mg·L−1 GBE group (GBE). The levels of glycogen and glucose were detected by ELISA, and the expression of PPARγ and GLUT4 proteins was detected by WB. Results A strong binding effect between GBE and PPARγ was revealed by network pharmacology. In in vivo experiments, the NaAsO2 group exhibited an elevated blood glucose compared to the control group, and the NaAsO2+GBE group showed a decreased blood glucose compared to the NaAsO2 group (P<0.01). The histopathological sections indicated severe liver structural damage in the arsenic exposure groups (NaAsO2 group and NaAsO2+GBE group), with varying staining intensity, partial liver cell necrosis, and diffuse red blood cell appearance. Both results of in vitro and in vivo experiments showed a decrease in glycogen synthesis and glucose uptake in the NaAsO2 groups compared to the control groups, which was alleviated in the NaAsO2+GBE group (P<0.01). The results of WB revealed inhibited PPARγ expression and reduced GLUT4 levels on the cell membrane, and all these changes were alleviated in the NaAsO2+GBE group (P<0.01). Conclusion This study findings suggest that GBE antagonizes arsenic exposure-induced hepatic IR by regulating the PPARγ/GLUT4 pathway, indicating that GBE has a protective effect on arsenic exposure-induced hepatic IR, and PPARγ may be a potential therapeutic target for arsenic exposure-induced hepatic IR.
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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been a major health burden in the world. So far, many strategies have been investigated to control the spread of COVID-19, including social distancing, disinfection protocols, vaccines, and antiviral treatments. Despite the significant achievement, due to the constantly emerging new variants, COVID-19 is still a great challenge to the global healthcare system. It is an urgent demand for the development of new therapeutics and technologies for containing the wild spread of SARS-CoV-2. Inhaled administration is useful for the treatment of lung and respiratory diseases, and enables the drugs to reach the site of action directly with benefits of decreased dose, improved safety, and enhanced patient compliance. Nanotechnology has been extensively applied in the prevention and treatment of COVID-19. In this review, the inhaled nanomedicines and antibodies, as well as intranasal nanodrugs, for the prevention and treatment of COVID-19 are summarized.
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The heparin polysaccharide nanoparticles block the interaction between heparan sulfate/S protein and inhibit the infection of both wild-type SARS-CoV-2 pseudovirus and the mutated strains through pulmonary delivery.Image 1.
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Objective To examine the distribution of bacterial species and antimicrobial susceptibility profile of pathogens in febrile neutropenic patients.Methods A total of 355 bacterial strains were isolated from febrile neutropenic patients in Shanghai General Hospital from January 2005 to December 2012. Antimicrobial susceptibility testing was done by Kirby-Bauer method. The susceptibility testing results were analyzed according to CLSI 2014 breakpoints.Results Gram-negative bacteria accounted for 70.4% of the 355 isolates, while gram-positive organisms accounted for 29.6%. The most common bacterial species werePseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii, Escherichia coli, Stenotrophomonas maltophiliaand Staphylococcus haemolyticus. Non-fermentative bacteria accounted for 53.2% of all the gram-negative bacterial isolates. All theEnterococcus and Staphylococcus isolates were susceptible to linezolid, vancomycin and teicoplanin. All theStaphylococcus strains were resistant to methicillin.P. aeruginosa isolates were relatively more susceptible to cefoperazone-sulbactam, piperacillin-tazobactam and cefepime (>70%) than imipenem (40.8%) and meropenem (59.2%). All theK. pneumoniae isolates were susceptible to imipenem and meropenem and more than 70% of the isolates were susceptible to cefoperazone-sulbactam, amikacin. More than 80% of theA. baumannii isolates were susceptible to carbapenems, cefoperazone-sulbactam, amikacin, ciprolfoxacin and aminoglycosides. All the E. coli isolates were susceptible to carbapenems and more than 70% were susceptible to cefoperazone-sulbactam and ceftazidime. More than 90% of theS. maltophilia strains were sensitive to levolfoxacin, minocycline, cefoperazone-sulbactam and trimethoprim-sulfamethoxazole.Conclusions Our data suggest that gram-negative bacteria, especiallyEnterobacteriaceae and non-fermentative bacteria, are still the primary pathogens in febrile neutropenic patients. Antimicrobial resistant strains are prevalent. Such data of bacterial species and antimicrobial susceptibility proifle of pathogens in febrile neutropenic patients are useful for empirical antimicrobial therapy of such infections.
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OBJECTIVE To analyze and compare the value of c-reactive protein(CRP) and body temperature in the infection diagnosis and severity of infection among the patients with malignant hematological disease.METHODS According to the microorganism detection and application of antibiotics,we divided the 119 patients into infection group and noninfection group from May 2004 to May 2005 in our ward.CRP and temperature of the patients were measured and.RESULTS There were 88 cases in the infection group and 31 cases in the noninfection group.The CRP plasma concentration had significant difference between too groups(P
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<p><b>OBJECTIVE</b>To investigate the efficacy of allogeneic peripheral blood stem cell transplantation (PBSCT) in the treatment of severe aplastic anemia (SAA) and severe infection.</p><p><b>METHODS</b>A patient with SAA and pseudomonas aeruginosa septicemia was treated with PBSCT from an HLA-identical sibling with cyclophosphamide (CY) and total body irradiation (TBI) for conditioning. The patient was infused with 20.3 x 10(8)/kg mononuclear cells including 61.0 x 10(6)/kg CD34(+) cells following the conditioning regimen.</p><p><b>RESULTS</b>Twelve days after PBSCT, the absolute neutrophil count (ANC) of 1.0 x 10(9)/L was achieved, with platelet count > 50 x 10(9)/L at twenty days. The donor origin of engraftment was confirmed by polymerase chain reaction (PCR) analysis of short tandem repeats at the end of the first, sixth and twelfth month. The patient's body temperature dropped to normal level when her ANC reached 0.5 x 10(9)/L on day 10, and the bacterial culture of blood sample became negative subsequently. Symptoms and signs of acute or chronic graft versus host disease (GVHD) were not observed in 30 months after PBSCT.</p><p><b>CONCLUSIONS</b>Hematopoiesis was reconstituted shortly after PBSCT. The combination of CY and TBI and the infusion of sufficient peripheral blood stem cells may contribute to the successful engraftment. PBSCT may be considered as the first choice when hematopoietic stem cell transplantation is needed for SAA patients complicated with severe infection.</p>