Anti-infection effects of heparin on SARS-CoV-2 in a diabetic mouse model

Severe acute respiratory syndrome coronavirus 2(SARSCo V-2)infection can result in more severe syndromes and poorer outcomes in patients with diabetes and obesity.However,the precise mechanisms responsible for the combined impact of coronavirus disease 2019(COVID-19)and diabetes have not yet been elucidated,and effective treatment options for SARS-Co V-2-infected diabetic patients remain limited.To investigate the disease pathogenesis,K18-h ACE2 transgenic(h ACE2^(Tg))mice with a leptin receptor deficiency(h ACE2-Lepr^(-/-))and high-fat diet(h ACE2-HFD)background were generated.The two mouse models were intranasally infected with a 5×10^(5) median tissue culture infectious dose(TCID_(50))of SARSCo V-2,with serum and lung tissue samples collected at 3days post-infection.The h ACE2-Lepr^(-/-)mice were then administered a combination of low-molecular-weight heparin(LMWH)(1 mg/kg or 5 mg/kg)and insulin via subcutaneous injection prior to intranasal infection with1×10^(4) TCID_(50)of SARS-Co V-2.Daily drug administration continued until the euthanasia of the mice.Analyses of viral RNA loads,histopathological changes in lung tissue,and inflammation factors were conducted.Results demonstrated similar SARS-Co V-2 susceptibility in h ACE2^(Tg)mice under both lean(chow diet)and obese(HFD)conditions.However,compared to the h ACE2-Lepr^(+/+)mice,h ACE2-Lepr^(-/-)mice exhibited more severe lung injury,enhanced expression of inflammatory cytokines and hypoxia-inducible factor-1α(HIF-1α),and increased apoptosis.Moreover,combined LMWH and insulin treatment effectively reduced disease progression and severity,attenuated lung pathological changes,and mitigated inflammatory responses.In conclusion,preexisting diabetes can lead to more severe lung damage upon SARS-Co V-2 infection,and LMWH may be a valuable therapeutic approach for managing COVID-19patients with diabetes.

A Facile Strategy to Fabricate Polysaccharide-Based Magnetic Hydrogel Based on Enamine Bond

of main observation and conclusion Magnetic hydrogels have found extensive applications in fields such as soft robotics,drug delivery and shape morphing.Here a facile method was fabricated to prepare polysaccharide-based magnetic hydrogels.The chitosan-Fe3O4 ferrofluid was obtained by dispersing carboxyl groups modified Fe3O4 nanoparticles uniformly in chitosan matrix.Subsequently,the magnetic polysaccharide hydrogel was obtained by simply mixing cellulose acetoacetate solution with chitosan-Fe3O4 ferrofluid.The structures and properties of the magnetic hydrogel were analyzed using Fourier-transform infrared spectroscopy,rheological recovery,responsiveness,and stability measurements.The results indicated that magnetic polysaccharide hydrogel showed pH responsiveness and excellent self-healing properties,and the hydrogel manifested outstanding stability under physiological conditions(37℃)for 72 h.In addition,the injectable polysaccharide-based hydrogel exhibited sensitive magnetic responsive and shape-shifting ability under an external magnetic field.Therefore,the strategy for the facile preparation of the magnetic polysaccharide-based hydrogel in this work could provide a benign and versatile method for achieving self-healing,responsive,injectable properties for the application in biomedical fields.