Coumaronochromones, flavanones, and isoflavones from the twigs and leaves of Erythrina subumbrans inhibit PTP1B and nitric oxide production.

A chemical investigation of the twigs and leaves of Erythrina subumbrans led to the isolation and structural elucidation of three coumaronochromones, erythrinasubumbrin A and (±)-erythrinasubumbrin B, five prenylated flavanones, (±)-erythrinasubumbrin C and erythrinasubumbrins D-F, and two prenylated isoflavones, (±)-5,4'-dihydroxy-[4,5-cis-4-ethoxy-5-hydroxy-6,6-dimethyl-4,5-dihydropyrano (2,3:7,6)]-isoflavone, in addition to 18 known analogues. Two extra cinnamylphenols previously only known as commercial synthetic products were also isolated and elucidated from a natural source for the first time, and assigned the trivial names erythrinasubumbrins G and H. Their structures were characterized by detailed analysis of spectroscopic data, including HRESIMS and 2D NMR. The absolute configurations of the previously undescribed isolates and the known coumaronochromone lupinol C were determined by specific rotation and electronic circular dichroism (ECD) data. All the isolates were evaluated for their inhibitory activities on protein tyrosine phosphatase 1 B (PTP1B) and nitric oxide (NO) production in lipopolysaccharide (LPS)-induced BV-2 microglial cells as well as their cytotoxicity against the HCT116 cell line. The pair of enantiomers, (+)-5,4'-dihydroxy-[4,5-cis-4-ethoxy-5-hydroxy-6,6-dimethyl-4,5-dihydropyrano (2,3:7,6)]-isoflavone and (-)-5,4'-dihydroxy-[4,5-cis-4-ethoxy-5-hydroxy-6,6-dimethyl-4,5-dihydropyrano (2,3:7,6)]-isoflavone, and the known compounds lupinol C, 4'-O-methyl-8-prenylnaringenin, glepidotin B, shuterin, parvisoflavones A, luteone, lupiwighteone, 2,3-dehydrokievitone, 6,8-diprenylgenistein, angustone A, and 2'-O-demethylbidwillol B exhibited different levels of PTP1B inhibitory activities with IC50 values ranging from 3.21 to 19.17 µM, while erythrinasubumbrin A, (-)-erythrinasubumbrin B, (+)-5,4'-dihydroxy-[4,5-cis-4-ethoxy-5-hydroxy-6,6-dimethyl-4,5-dihydropyrano (2,3:7,6)]-isoflavone, (-)-5,4'-dihydroxy-[4,5-cis-4-ethoxy-5-hydroxy-6,6-dimethyl-4,5-dihydropyrano (2,3:7,6)]-isoflavone, and the known compounds lupinol C, 8-prenylnaringenin, macatrichocarpin A, alpinumisoflavone, and 2'-O-demethylbidwillol B substantially inhibited NO production in BV-2 microglial cells. In addition, 8-prenylnaringenin showed weak cytotoxicity with an IC50 value of 9.13 µM. This is the first report of PTP1B inhibitory activity for a coumaronochromone.

A pilot study of viscoelastic agent to prevent recurrent vitreous hemorrhage after vitrectomy for proliferative diabetic retinopathy.

BACKGROUND: To evaluate the possibilty of preventing recurrent vitreous hemorrhage (RVH) after vitrectomy in proliferative diabetic retinopathy (PDR) patients with unabsorbed vitreous hemorrhage (VH) by intravitreal injection of viscoelastic agent (VA) at the end of the surgery and compared its effect with triamcinolone acetonide (TA). METHODS: This was a pilot prospective, observational study. PDR patients with VH who underwent vitrectomy were assigned to 3 groups according to the tamponade applicated at the end of the surgery, including VA group (intravitreally injected 1 ml VA if the retina was prone to bleed during the operation), TA group (intravitreally injected 2 mg TA when there was much exudates), or balanced salt solution (BSS) group (no tamponade). Then postoperative follow-up was performed routinely until 6 months after surgery. The primary outcome was the incidence of RVH, secondary outcome were the best-corrected visual acuity (BCVA) and introcular pressure (IOP). Cataract formation and other complication were also assessed. RESULTS: A total of 68 eyes, from 68 patients, were included. 18,18,32 eyes were enrolled in the VA group, TA group and BSS group, respectively. The integral incidence of RVH after vitrectomy was 5.6%, 5.6% and 12.5% respectively (P = 0.602). There was no early RVH in VA or TA group, whereas 3 early RVHs were identified in BSS group, however there was no significant difference (P = 0.171). Every group had one late RVH case. In all groups, final BCVA showed significant improvement compared to baseline. BCVA at any postoperative visit showed no significant differences among 3 groups. Mean IOP was higher 1 week after surgery in VA group compared with the other groups; however, in other times the differences were not significant. No cataract formation and other complication was noted in 3 groups. CONCLUSION: Intravitreal injection of VA or TA at the end of vitrectomy for PDR patients with unabsorbed VH tend to reduce the incidence of early RVH after vitrectomy similarly. As VA was preferred to applicate in the eyes that were prone to bleed, intravitreal injection of VA at the end of vitrectomy might be a promising method for preventing RVH in PDR patients.

MRI-visible enlarged perivascular spaces: imaging marker to predict cognitive impairment in older chronic insomnia patients.

OBJECTIVE: Perivascular spaces (PVS), components of the glymphatic system in the brain, have been known to be important conduits for clearing metabolic waste, and this process mainly increases during sleep. Sleep disruption might result in PVS dysfunction and cognitive impairment. In this study, we aim to explore whether MRI-visible enlarged perivascular spaces (EPVS) could be imaging markers to predict cognitive impairment in chronic insomnia patients. METHOD: We obtained data from 156 patients with chronic insomnia and 79 age-matched healthy individuals. Using T2-weighted MRI images, visible EPVS in various brain regions were measured and analyzed. The associations between EPVS numbers and cerebrospinal fluid (CSF) ß-amyloid 42 (Aß42), total tau (t-tau), and phosphorylated tau (p-tau) level in chronic insomnia patients were evaluated. RESULT: Our results showed that MRI-visible EPVS in the frontal cortex, centrum semiovale, basal ganglia, and hippocampus of chronic insomnia patients with impaired cognition (ICG) significantly increased than that in normal cognition (NCG) patients. The increased MRI-visible EPVS in the frontal cortex, centrum semiovale, and basal ganglia were also associated with the increased CSF Aß42, t-tau, and p-tau level in ICG patients. MRI-visible EPVS in the basal ganglia and centrum semiovale had high sensitivity and specificity in distinguishing ICG chronic insomnia patients from those with NCG. CONCLUSION: Our study indicated that MRI-visible EPVS in the basal ganglia and centrum semiovale might be valuable imaging markers to predict cognitive impairment in chronic insomnia patients. It will be meaningful to discern those cognitive decline patients in preclinical stage and take some measures to prevent disease progression. KEY POINTS: • Increased MRI-visible EPVS were associated with the increased CSF Aß42, t-tau, and p-tau level in older chronic insomnia patients with impaired cognition.

[Role of BET Bromodomain in Hematopoietic Differentiation from hESCs].

OBJECTIVE: To explore the role of bromodomain and extra terminal (BET) bromodomain in hematopoietic differentiation from human enbryonic stem cells (hESC). METHODS: The effect of BET hematopoietic inhibitor I-BET151 on hematopoietic differentiation from hESC was detected by using a monolayer hematopoietic defferentiation model, immunofluorescence, flow cytometry and real-time PCR; moreover the role of I-BET151 in process of hematopoietic differentiation was explored by adding I-BET151 in different differentiation stages. RESULTS: The analysis results of immunofluorescence, flow cytometry and real-time PCR showed that I-BET 151 significantly inhibited the generation of CD43 positive hematopoietic stem and progenitor cells (HSPCs). It was found that the addition of I-BET 151 in different stages, including APLNR+ lateral plate mesoderm production, CD34+CD31+ hemogenic endothelium (HEP) generation and endothelial-to-hematopoietic transition, significantly suppressed the generation of CD43 positive hematopoietic progenitor cells. CONCLUSION: I-BET 151 inhibites hematopoietic differentiation from hESCs at several stages, suggesting that the BET bromodomain plays important roles in multiple stages of hematopoietic differentiation from hESCs.

[DMSO Promotes Hematopoietic Differentiation of Human Embryonic Stem Cells in vitro].

OBJECTIVE: To explore the role of dimethyl sulfoxide (DMSO) in the hematopoietic differentiation of human embryonic stem cells (hESCs). METHODS: The role of DMSO in hematopoietic differentiation of hESC was investigated by using a established stepwise hematopoietic differentiation system from hESC, immunofluorescouse assay and flow cytometry. Furthermore, the window phase of DMSO action was explored by adding it to the different stage of hematopoietic differentiation. RESULTS: Immunofluorescence and flow cytometry analysis showed that DMSO significantly promoted the generation of CD43+ hematopoietic progenitor cells (HPC). The flow cytometry demonstrated that DMSO profoundly promoted the generation of APLNR+ lateral plate mesoderm cells and CD31+CD34+ hemogenic endothelium progenitors (HEP). The addition of DMSO in the window phase of lateral plate mesoderm cell generation could markedly improve the generation of hematopoietic progenitor cells. CONCLUSION: DMSO promotes hematopoietic differentiation of hESC through enhancing the generation of APLNR positive lateral plate mesoderm cells. The addition of DMSO in the window phase of lateral plate mesoderm cell generation can significantly improve the generation of hematopoietic progenitor cells.