Protective effects of total flavonoids from Flos Puerariae on retinal neuronal damage in diabetic mice.

PURPOSE: To investigate the potential protective effects of total flavonoids from Flos Puerariae (TFF) on retinal neural cells in diabetic mice. METHODS: C57BL/6J mice were intraperitoneally injected with streptozotocin to generate type I diabetes in a murine model, as indicated by blood glucose levels ≥11.1 mmol/l. TFF was administered intragastrically at a dose of 50, 100, or 200 mg/kg/day. After 10 weeks of administration, the mice were euthanized, and the eyes were dissected. Retinal histology was examined, and the thickness of the retina was measured. Ultrastructural changes in the retinal ganglion cells and capillary basement membrane were observed with electron microscopy. Apoptosis of retinal neural cells was determined with the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling assay. Bax and Bcl-2 expression in the retinal tissues was determined with immunohistochemical staining and western blotting. RESULTS: Compared with the diabetic mice, the blood glucose level decreased (p<0.01) and the bodyweight increased (p<0.05) in the 100 and 200 mg/kg TFF-treated groups. The thickness of the retina significantly increased (p<0.01), and the retinal capillary basement membrane (BM) thickness was reduced in the 100 and 200 mg/kg TFF-treated diabetic mice (DM). The 100 and 200 mg/kg TFF treatments also attenuated the diabetes-induced apoptosis of retinal neural cells. Consistent with these effects, TFF treatment decreased the Bax expression level and, concurrently, increased the ratio of Bcl-2 to Bax. CONCLUSIONS: TFF attenuated diabetes-induced apoptosis in retinal neurons by inhibiting Bax expression and increasing the ratio of Bcl-2 to Bax, which suggests that TFF might prevent retinal neuronal damage in diabetes mellitus.

Application of Three-Dimensional Arterial Spin Labeling Technique in the Assessment of Cerebral Blood Perfusion in Patients with Middle Cerebral Artery Occlusion: Analysis of Clinical Implications and Prognostic Factors.

Objective: To explore the value of three-dimensional- (3D-) arterial spin labeling (ASL) technique in evaluating cerebral perfusion in patients with unilateral middle cerebral artery occlusion (MCAO) and to observe the influencing factors of poor prognosis via long-term follow-up of patients who survived the disease. Methods: The clinical data of 60 patients with unilateral middle cerebral artery (MCA) M1 segment occlusion diagnosed by magnetic resonance angiography (MRA) from January 2018 to January 2022 were retrospectively analyzed. All patients were examined by routine MRI, MRA, and 3D-ASL, in which two postlabeling delays (PLDs; 1525 ms and 2525 ms) were used in 3D-ASL. Cerebral blood flow (CBF) in the regions of interest (ROIs) of MCA on the affected side and the mirror side was measured. The clinical data and laboratory indexes of patients were collected and evaluated by clinical scales. With the modified Rankin Score (mRS) as the outcome indicator, patients were assigned to either the poor or the good prognosis group to analyze the factors influencing patient prognosis via univariate and multivariate analyses. Results: Among unilateral MCAO patients, there was a significant difference in the CBF of the affected side between the PLD 1525 ms and 2525 ms groups (P < 0.05), but there was no significant difference in the CBF of the mirror side (P > 0.05). Compared with the mirror side, 43 cases (71.7%) of the affected CBF presented with hypoperfusion, 9 cases (15.0%) with normal perfusion, and 8 cases (13.3%) with hyperperfusion. Age, NIHSS score, collateral circulation, and homocysteine (Hcy) were identified by multivariate Logistic regression analysis as independent risk factors for adverse outcomes. Conclusion: MCAO can lead to cerebral blood perfusion decline, and 3D-ASL technique can evaluate the post-MCAO cerebral blood perfusion level. Old age, high NIHSS scores, poor collateral circulation, and high Hcy levels are associated with poor clinical outcomes.

Safety but Limited Efficacy of Ensartinib in ROS1-Positive NSCLC: A Single-Arm, Multicenter Phase 2 Study.

INTRODUCTION: Some ALK inhibitors with good inhibition of ROS1 in preclinical studies have been reported to be possibly beneficial in ROS1-positive NSCLC. In this work, we studied the efficacy and safety of ensartinib in the treatment of patients with ROS1-positive NSCLC. METHODS: The exploratory study was a phase 2, single-arm, multicenter design (NCT03608007). Patients with ROS1-positive NSCLC with a previous chemotherapy line number of less than or equal to 1 who received ensartinib at the dose of 225 mg once daily were enrolled. The primary end point was objective response rate evaluated by an investigator per Response Evaluation Criteria in Solid Tumors version 1.1. RESULTS: From June 2018 to July 2019, a total of 59 patients were enrolled at 23 centers in the People's Republic of China. At the time of data cutoff, the median follow-up was 19.8 months (range: 0.8-22.5). The median objective response rate was 27.0 % (95 % confidence interval [CI]: 13.8-44.1) with 10 partial responses. Median duration of response was 4.8 months (95 % CI: 1.8-10.8). The median progression-free survival was 4.6 months (95 % CI: 4.0-6.4). The median overall survival was not estimable (95 % CI: 14.9-not estimable). Of four patients with brain metastases, intracranial disease control was reported in three (75.0 %, 95 % CI: 19.4-99.4). The most common treatment-related adverse events (TRAEs) were rash and liver enzyme abnormalities, with good prognosis after adjustment for dosage and concomitant medication. Most of the TRAEs were of grades 1 to 2, and incidence of grade greater than or equal to 3 TRAEs was 25.4 %. CONCLUSIONS: Ensartinib had a modest efficacy in patients with ROS1-positive NSCLC with an acceptable safety profile.

Flos Puerariae Extract Ameliorates Cognitive Impairment in Streptozotocin-Induced Diabetic Mice.

Objective. The effects of Flos Puerariae extract (FPE) on cognitive impairment associated with diabetes were assessed in C57BL/6J mice. Methods. Experimental diabetic mice model was induced by one injection of 50 mg/kg streptozotocin (STZ) for 5 days consecutively. FPE was orally administrated at the dosages of 50, 100, or 200 mg/kg/day, respectively. The learning and memory ability was assessed by Morris water maze test. Body weight, blood glucose, free fatty acid (FFA) and total cholesterol (TCH) in serum, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and acetylcholinesterase (AChE) activities in cerebral cortex and hippocampus were also measured. Results. Oral administration of FPE significantly improved cognitive deficits in STZ-induced diabetic mice. FPE treatment also maintained body weight and ameliorated hyperglycemia and dyslipidemia in diabetic mice. Additionally, decreased MDA level, enhanced CAT, and GSH-Px activities in cerebral cortex or hippocampus, as well as alleviated AChE activity in cerebral cortex, were found in diabetic mice supplemented with FPE. Conclusion. This study suggests that FPE ameliorates memory deficits in experimental diabetic mice, at least partly through the normalization of metabolic abnormalities, ameliorated oxidative stress, and AChE activity in brain.

Flos Puerariae extract prevents myocardial apoptosis via attenuation oxidative stress in streptozotocin-induced diabetic mice.

BACKGROUND: Diabetic cardiomyopathy (DCM) suggests a direct cellular insult to myocardium. Apoptosis is considered as one of the hallmarks of DCM. Oxidative stress plays a key role in the pathogenesis of DCM. In this study, we explored the prevention of myocardial apoptosis by crude extract from Flos Puerariae (FPE) in experimental diabetic mice. METHODS: Experimental diabetic model was induced by intraperitoneally injection of streptozotocin (STZ, 50 mg/kg/day) for five consecutive days in C57BL/6J mice. FPE (100, 200 mg/kg) was orally administrated once a day for ten weeks. Cardiac structure changes, apoptosis, superoxide production, NADPH oxidase subunits expression (gp91phox, p47phox, and p67phox), and related regulatory factors were assessed in the heart of mice. RESULTS: Diabetic mice were characterized by high blood glucose (≥11.1 mmol/L) and reduced body weight. In the end of the experiment, aberrant myofilament structure, as well as TUNEL positive cardiac cells coupled with increased Bax/Bcl-2 ratio and Caspase-3 expression was found in diabetic mice. Moreover, ROS formation, the ratio of NADP+/NADPH and NADPH oxidase subunits expression of gp91phox and p47phox, lipid peroxidation level was significantly increased, while antioxidant enzyme SOD and GSH-Px activity were reduced in the myocardial tissue of diabetic mice. In contrast, treatment with FPE resulted in a normalized glucose and weight profile. FPE administration also preserved myocardial structure and reduced apoptotic cardiac cell death in diabetic mice. The elevated markers of oxidative stress were significantly reversed by FPE supplementation. Further, FPE treatment markedly inhibited the increased Bax/Bcl-2 ratio and Caspase-3 expression, as well as suppressed JNK and P38 MAPK activation in the heart of diabetic mice. CONCLUSIONS: Our data demonstrate for the first time that FPE may have therapeutic potential for STZ-induced diabetic cardiomyopathy through preventing myocardial apoptosis via attenuation oxidative stress. And this effect is probably mediated by JNK and P38 MAPK signaling pathway.