ABSTRACT
Pulmonary hypertension (PH) is an insidious pulmonary vasculopathy with high mortality and morbidity and its underlying pathogenesis is still poorly delineated. The hyperproliferation and apoptosis resistance of pulmonary artery smooth muscle cells (PASMCs) contributes to pulmonary vascular remodeling in pulmonary hypertension, which is closely linked to the downregulation of fork-head box transcriptional factor O1 (FoxO1) and apoptotic protein caspase 3 (Cas-3). Here, PA-targeted co-delivery of a FoxO1 stimulus (paclitaxel, PTX) and Cas-3 was exploited to alleviate monocrotaline-induced pulmonary hypertension. The co-delivery system is prepared by loading the active protein on paclitaxel-crystal nanoparticles, followed by a glucuronic acid coating to target the glucose transporter-1 on the PASMCs. The co-loaded system (170 nm) circulates in the blood over time, accumulates in the lung, effectively targets the PAs, and profoundly regresses the remodeling of pulmonary arteries and improves hemodynamics, leading to a decrease in pulmonary arterial pressure and Fulton's index. Our mechanistic studies suggest that the targeted co-delivery system alleviates experimental pulmonary hypertension primarily via the regression of PASMC proliferation by inhibiting cell cycle progression and promoting apoptosis. Taken together, this targeted co-delivery approach offers a promising avenue to target PAs and cure the intractable vasculopathy in pulmonary hypertension.
ABSTRACT
Cellular nanovesicles which are referred to as cell-derived, nanosized lipid bilayer structures, have emerged as a promising platform for regulating immune responses. Owing to their outstanding advantages such as high biocompatibility, prominent structural stability, and high loading capacity, cellular nanovesicles are suitable for delivering various immunomodulatory molecules, such as small molecules, nucleic acids, peptides, and proteins. Immunomodulation induced by cellular nanovesicles has been exploited to modulate immune cell behaviors, which is considered as a novel cell-free immunotherapeutic strategy for the prevention and treatment of diverse diseases. Here we review emerging concepts and new advances in leveraging cellular nanovesicles to activate or suppress immune responses, with the aim to explicate their applications for immunomodulation. We overview the general considerations and principles for the design of engineered cellular nanovesicles with tailored immunomodulatory activities. We also discuss new advances in engineering cellular nanovesicles as immunotherapies for treating major diseases.
ABSTRACT
Invasive fungal infections (IFIs) represent a growing public concern for clinicians to manage in many medical settings, with substantial associated morbidities and mortalities. Among many current therapeutic options for the treatment of IFIs, amphotericin B (AmB) is the most frequently used drug. AmB is considered as a first-line drug in the clinic that has strong antifungal activity and less resistance. In this review, we summarized the most promising research efforts on nanocarriers for AmB delivery and highlighted their efficacy and safety for treating IFIs. We have also discussed the mechanism of actions of AmB, rationale for treating IFIs, and recent advances in formulating AmB for clinical use. Finally, this review discusses some practical considerations and provides recommendations for future studies in applying AmB for combating IFIs.
ABSTRACT
Objective To explore the variations and prognostic factors of hyperhomocysteinaemia in ischemic cerebral apoplexy for the youth who administrated vitamin B6,vitamin B12 and folic acid at pretherapy and post-treatment.Methods One hundred and twenty cases of young patients with ischemic cerebral apoplexy in the Pinggu Hospital of Capital University from January 2003 to December 2013 as case group(intervention group,60 cases and 60 cases of non-intervention group),while 120 youth volunteers with the same period and age without neurological diseases as a control group.Both groups patients were detected for hyperhomocysteinaemia,folic acid and vitamin B12.The non-intervention group was administrated basic treatment,while the intervention group administrated vitamin B6,vitamin B12 and folic acid on this basis.The hyperhomocysteinaemia,folic acid and vitamin B12 were detected repetitively after four weeks.Results Compared with control group,the hyperhomocysteinaemia in ischemic cerebral apoplexy group for the youth had increased significantly ((10.2 ± 3.1) μmmol/L vs.(21.3 ± 4.5) μmmol/L,P ＜ 0.05).The hyperhomocysteinaemia,folic acid and vitamin B12 had no significant differences between intervention group and non-intervention group (P ＞ 0.05).After replenished vitamin B6,vitamin B12 and folic acid,the hyperhomocysteinaemia had decreased significantly ((10.5 ± 3.0) μmnol/L) in intervention group.Folic acid ((6.5±2.8)μg/L) and vitamin B12(450.2±155.6) ng/L) had increased significantly(P＜0.05).Conclusion The hyperhomocysteinaemia increased in ischemic cerebral apoplexy for the youth.It is that hyperhomocysteinaemia decreased by replenished vitamin B6,vitamin B12 and folic acid which make for prognosis in ischemic cerebral apoplexy for the youth.
ABSTRACT
OBJECTIVE To evaluate the efficacy,the eradication rates of pathogens and safety of levofloxacin in patients with community-acquired pneumonia(CAP) in comparison with therapy using a combination of cefuroxime plus azithromycin.METHODS Fifty five patients with CAP were randomly divided into two groups: levofloxacin alone and cefuroxime plus azithromycin,and the efficacy,the eradication rates of pathogens and the rates of side effects were observed.RESULTS From 30 patients in the levofloxacin group,25 patients(83.3%) were clinically cured and 3 patients(10.0%) were improved.And from 25 patients in the cefuroxime plus azithromycin group, 20 patients(80.0%) were clinically cured and 3 patients(12.0%) were improved. The eradication rates of pathogens were 85.7% and 88.9%,respectively.And the rates of side effects were 3.3% and 4.0%,respectively.CONCLUSIONS There are no significant differences in the efficacy,the eradication rates of pathogens and safety between 2 groups in treating community-acquired pneumonia.