Background: Angiogenesis and energy metabolism mediated by adipose mesenchymal stem cell-derived exosomes (AMSC-exos) are promising therapeutics for vascular diseases. Objectives: The current study aimed to explore whether AMSC-exos have therapeutic effects on oxygen and glucose deprivation (OGD) human umbilical vein endothelial cells (HUVECs) injury by modulating the SIX1/HBO1 signaling pathway to upregulate endothelial cells (E.C.s) glycolysis and angiogenesis Methods: Methods: AMSC-exos were isolated and characterized following standard protocols. AMSC-exos cytoprotective effects were evaluated in the HUVECs-OGD model. The proliferation, migration, and tube formation abilities of HUVECs were assessed. The glycolysis level was evaluated by detecting lactate production and ATP synthesis. The expressions of HK2, PKM2, VEGF, HIF-1α, SIX1, and HBO1 were determined by western blotting, and finally, the SIX1 overexpression vector or small interfering RNA (siRNA) was transfected into HUVECs to assess the change in HBO1 expression. Results: Our study revealed that AMSC-exos promotes E.C.s survival after OGD, reducing E.C.s apoptosis while strengthening E.C.'s angiogenic ability. AMSC-exos enhanced glycolysis and reduced OGD-induced ECs injury by modulation of the SIX1/HBO1 signaling pathway, which is a novel anti-endothelial cell injury role of AMSC-exos that regulates glycolysis via activating the SIX1/HBO1 signaling pathway. Conclusion: The current study findings demonstrate a useful angiogenic therapeutic strategy for AMSC-exos treatment in vascular injury, thus providing new therapeutic ideas for treating ischaemic diseases.
Abstract Introduction There is conflicting evidence whether high‐density lipoprotein cholesterol (HDL‐C) is a risk factor for Alzheimer's disease (AD) and dementia. Genetic variation in the cholesteryl ester transfer protein ( CETP ) locus is associated with altered HDL‐C. We aimed to assess AD risk by genetically predicted HDL‐C. Methods Ten single nucleotide polymorphisms within the CETP locus predicting HDL‐C were applied to the International Genomics of Alzheimer's Project (IGAP) exome chip stage 1 results in up 16,097 late onset AD cases and 18,077 cognitively normal elderly controls. We performed instrumental variables analysis using inverse variance weighting, weighted median, and MR‐Egger. Results Based on 10 single nucleotide polymorphisms distinctly predicting HDL‐C in the CETP locus, we found that HDL‐C was not associated with risk of AD ( P > .7). Discussion Our study does not support the role of HDL‐C on risk of AD through HDL‐C altered by CETP . This study does not rule out other mechanisms by which HDL‐C affects risk of AD.
8173 Background: About 80% of children treated for ALL will be long term survivors. The estimated cumulative risk of a SMN is 2% to 3.3% 15 yrs after diagnosis. Methods: A review of the literature of 25,907 children treated for ALL revealed 274 SMN (1.07%). Results: The most frequently observed SMN are shown below: Others included CML(3), breast cancer (4), malignant histiocytosis (2), ovarian cancer (2), one case each of nephroblastoma, mucoepidermoid CA, bladder CA, malignant teratoma, leimyosarcoma of lung, and 22 unknown cases. In the lymphoma group there was an equal number of NHL and Hodgkins (10). In the AML/MDS group most were AML(26). Of all cases of SMN 62% recieved RT and the risk of a SMN appears to be dose related. Of significance is the fact that the overall survival rate for those patients with reported long term follow is 57.3% (101/176). The Ewings Family tumors and in particular PNET of bone are rare SMN. Of these 25,901 children treated for ALL there is only one case report of a PNET of bone. Our case of a chest wall PNET developing in an 8-yr-old boy one yr after completing therapy for standard risk ALL is the second case reported and the first one associated with germline and tumor cell p53 mutation. . Our patient did not receive RT and therefore can be excluded as a contributing factor. Exposure to anthracyclines and alkylating agents was minimal (75mg/m2 and 1gm/m2 of adriamycin and cytoxan respectively). Conclusions: We conclude that germline p53 mutation played a major role in the development of this rarely observed SMN and that cases of SMN in pediatric patients should be evaluated for p53 mutation. Overall long term survival for patients with SMN after treatment for ALL is encouraging at 57% and determination of p53 may influence therapeutic and prognostic considerations. One percent of children treated for ALL will develop SMN, the decrease use of RT in children with ALL should result in even a lower number of SMN. No significant financial relationships to disclose.
Abstract Sickle cell nephropathy results in chronic kidney disease (CKD), which is associated with significant morbidity and mortality in sickle cell anemia (SCA). Albuminuria is an early manifestation of sickle nephropathy; however, little is known about progression of albuminuria or its correlation with glomerular filtration rate (GFR) decline or CKD. We studied nephropathy progression in 303 SCA participants in a prospective, multicenter, longitudinal study. We collected steady-state urine and serum samples yearly and assessed albumin/creatinine ratio (ACR), estimated GFR (eGFR), and SCA and nephropathy biomarkers. Participants with albuminuria (ACR ≥30 mg/g) for ≥2 annual measurements were classified as having persistent albuminuria (PA). At baseline (mean age, 21 years; range, 2-64 years), 32% had albuminuria. In longitudinal multivariate analysis, ACR was associated with sex, anemia, older age, and higher bilirubin and kidney injury molecule-1 levels. Albuminuria increased with age by 3.5 mg/g per year (P < .0001). Of 175 participants with ≥3 annual samples, 81% with baseline albuminuria ≥100 mg/g developed PA. Decreased eGFR and adult CKD were associated with PA (P = .002 and P = .02, respectively), but not with baseline albuminuria. Rate of eGFR decline was steeper among adults (but not children) with albuminuria, compared with those without (P = .02). Participants with PA were more likely to have rapid eGFR decline compared with those without (P = .03). In this longitudinal study, albuminuria progressed with age, and adults with albuminuria had worse eGFR decline than those without. Albuminuria ≥100 mg/g predicted PA, which was associated with rapid eGFR decline and CKD development in adults with SCA. This trial was registered at www.clinicaltrials.gov as #NCT02239016.
Gliofibromas are bimorphic tumors of the central nervous system. Although they are composed of astrocytic and fibroblastic elements, their histogenesis is not clear. An attempt has been made to classify the tumors as low- or high-grade based on morphology and proliferative labeling index, but the clinical behavior and the optimal therapeutic strategies remain unknown. Although they are considered benign, the authors' review shows a 23% mortality rate. The authors report the successful use of carboplatinum and vincristine as treatment of this disease.
