ABSTRACT
Acute lung injury (ALI), as a common clinical emergency, is pulmonary edema and diffuse lung infiltration caused by inflammation. The lack of non-invasive alert strategy, resulting in failure to carry out preventive treatment, means high mortality and poor prognosis. Stimulator of interferon genes (STING) is a key molecular biomarker of innate immunity in response to inflammation, but there is still a lack of STING-targeted strategy. In this study, a novel STING-targeted PET tracer, [18F]FBTA, was labeled with high radiochemical yield (79.7 ± 4.3%) and molar activity (32.5 ± 2.9 GBq/μmol). We confirmed that [18F]FBTA has a strong STING binding affinity (Kd = 26.86 ± 6.79 nmol/L) and can be used for PET imaging in ALI mice to alert early lung inflammation and to assess the efficacy of drug therapy. Our STING-targeted strategy also reveals that [18F]FBTA can trace ALI before reaching the computed tomography (CT) diagnostic criteria, and demonstrates its better specificity and distribution than [18F]fluorodeoxyglucose ([18F]FDG).
ABSTRACT
Although mesenchymal stem cell-derived exosomes (MSC-exos) have been shown to have therapeutic effects in experimental periodontitis, their drawbacks, such as low yield and limited efficacy, have hampered their clinical application. These drawbacks can be largely reduced by replacing the traditional 2D culture system with a 3D system. However, the potential function of MSC-exos produced by 3D culture (3D-exos) in periodontitis remains elusive. This study showed that compared with MSC-exos generated via 2D culture (2D-exos), 3D-exos showed enhanced anti-inflammatory effects in a ligature-induced model of periodontitis by restoring the reactive T helper 17 (Th17) cell/Treg balance in inflamed periodontal tissues. Mechanistically, 3D-exos exhibited greater enrichment of miR-1246, which can suppress the expression of Nfat5, a key factor that mediates Th17 cell polarization in a sequence-dependent manner. Furthermore, we found that recovery of the Th17 cell/Treg balance in the inflamed periodontium by the local injection of 3D-exos attenuated experimental colitis. Our study not only showed that by restoring the Th17 cell/Treg balance through the miR-1246/Nfat5 axis, the 3D culture system improved the function of MSC-exos in the treatment of periodontitis, but also it provided a basis for treating inflammatory bowel disease (IBD) by restoring immune responses in the inflamed periodontium.
Subject(s)
Humans , Colitis , Exosomes , Periodontitis/therapy , Periodontium , T-Lymphocytes, Regulatory , Th17 CellsABSTRACT
Objective To investigate the effects of 3% hypertonic saline (HTS) on cerebrospinal fluid pressure (CSFP), hemodynamics and electrolytes and the feasibility of reducing intracranial pressure (ICP) with 3% HTS in patients with brain tumor. Methods This study was approved by our institutional ethics committee. Forty consenting ASA Ⅰ or Ⅱ patients of both sexes (23 males, 17 females) undergoing elective surgical excision of supratentorial glioma were randomly divided into 2 groups (n =20 each):3% HTS group and 20% mannitol group. The patients were fasted for 12 h before operation and premedicated with intramuscular phenobarbital 0.1 g and scopolamine 0.3 mg. Anesthesia was induced with midazolam 1.5-2.0 mg, fentanyl 3 ?g?kg-1,2.5% sodium pentothal 4-6 mg?kg-1 and vecuronium 0.1 mg?kg-1. The patients were mechanically ventilated (VT= 8-10 ml?kg-1, RR = 12 bpm, PETCO2 = 30-35 mm Hg) after tracheal intubation. Anesthesia was maintained with isoflurane inhalation and vecuronium infusion at 0.05 mg?kg-1?h-1. A bolus of fentanyl 4 ?g?kg-1 was given i.v. 5 min before incision. Before induction of general anesthesia a 17 G catheter was inserted into subarachnoid space at L3,4 for measurement of CSFP. Left radial artery and right internal jugular vein were cannulated for BP and CVP monitoring and blood sampling. When end-tidal isoflurane concentration was maintained at 1 MAC and hemodynamics stabilized for 15 min,3% HTS 5.35 ml?kg-1 or 20% mannitol 1 g?kg-1 was infused i.v. over 15 min. MAP, HR, CVP and urine output were measured and recorded and arterial blood samples were taken for blood gas analysis and determination of plasma Na+ and K+ concentrations, pH and plasma osmotic pressure before infusion (T0 , baseline) and 15, 30, 60, 90 and 120 min after infusion (T1-5). CSFP was measured at T0-4 and cerebral perfusion pressure (CPP) was calculated (CPP = MAP - ICP).Results The two groups were comparable with regard to sex, age, body weight and the extent of cerebral midline deviation (