Indole Diterpenes from Mangrove Sediment-Derived Fungus Penicillium sp. UJNMF0740 Protect PC12 Cells against 6-OHDA-Induced Neurotoxicity via Regulating the PI3K/Akt Pathway.

In our chemical investigation into Penicillium sp. UJNMF0740 derived from mangrove sediment, fourteen indole diterpene analogs, including four new ones, are purified by multiple chromatographic separation methods, with their structures being elucidated by the analyses of NMR, HR-ESIMS, and ECD data. The antibacterial and neuroprotective effects of these isolates were examined, and only compounds 6 and 9 exhibited weak antibacterial activity, while compounds 5, 8, and 10 showed protective effects against the injury of PC12 cells induced by 6-hydroxydopamine (6-OHDA). Additionally, compound 5 could suppress the apoptosis and production of reactive oxygen species (ROS) in 6-OHDA-stimulated PC12 cells as well as trigger the phosphorylation of PI3K and Akt. Taken together, our work enriches the structural diversity of indole diterpenes and hints that compounds of this skeleton can repress the 6-OHDA-induced apoptosis of PC12 cells via regulating the PI3K/Akt signaling pathway, which provides evidence for the future utilization of this fascinating class of molecules as potential neuroprotective agents.

Prognostic factors affecting the ruptured intracranial aneurysms: A 9-year multicenter study in Fujian, China.

BACKGROUND: A multicenter retrospective study was conducted to explore the factors affecting short-term prognosis and long-term outcomes of intracranial aneurysms (IA) rupture. Further, the prognosis prediction model was constructed based on survival analysis, contributing to the development of prevention strategies for aneurysmal subarachnoid hemorrhage. METHODS: Data of 1280 patients with IA rupture were gathered between 2014 and 2022 in Fujian, China. Logistic regression was implemented to study the short-term prognostic factors of IA rupture. Survival analysis of 911 patients among them was performed to explore the long-term outcome status by Cox risk assessment. Nomogram prognosis models were constructed using R software. RESULTS: The findings displayed that blood type O (OR = 1.79; P = 0.019), high systolic pressure (OR = 1.01; P < 0.001), Glasgow Coma score (GCS) 9-12 (OR = 2.73; P = 0.022), GCS < 9 (OR = 3.222; P = 0.006), diabetes (OR = 2.044; P = 0.040), and high white blood cell count (OR = 1.059, P = 0.040) were core influencing factors for poor short-term prognosis. Survival analysis revealed that age > 60 years (HR = 2.87; P = 0.001), hypertension (HR = 1.95; P = 0.001), conservative (HR = 6.89; P < 0.001) and endovascular treatment (HR = 2.20; P = 0.001), multiple ruptured IAs (HR = 2.37; P = 0.01), Fisher 3 (HR = 1.68; P = 0.09), Fisher 4 (HR = 2.75; P = 0.001), and Hunt-Hess 3 (HR = 0.55; P = 0.05) were the major risk factors for terrible long-term outcomes. CONCLUSIONS: People over 60 years with characteristics of type O blood, high systolic pressure, diabetes, high white blood cell count, and onset GCS < 12 will have more complications and a worse short-term prognosis. Those aged > 60 years with hypertension, conservative and endovascular treatment, multiple ruptured IAs, Fisher ≥ 3 and Hunt-Hess 3 have a greater risk of poor long-term prognosis.

[Soil Enzyme Stoichiometric Characteristics of Pinus massoniana Plantations at Different Stand Ages in Mid-subtropical Areas].

Soil enzyme activity is an important index to characterize the nutrient requirements and nutrient limitations of soil microorganisms. In this study, Pinus massoniana plantations of different stand ages (9, 17, 26, 34, and 43 a) in mid-subtropical China were taken as the research object; the activities of ß-glucosidase (BG), N-acetyl-ß-glucosaminidase (NAG), leucine amino-peptidase (LAP), acid phosphatase (AP), polyphenol oxidase (POX), and peroxidase (POD) were determined; and soil enzyme stoichiometric ratios were also calculated to investigate the soil microbial nutrient limitations of P. massoniana plantation development. The results showed that the activities of BG, NAG, AP, POX, and POD were enhanced with the increase in stand age, and the activity of LAP was the lowest at 17 a, which showed a significant difference and fluctuated among the neighboring stand ages. The soil enzyme C:N:P stoichiometric ratio was 1:1:0.56, which deviated from the global ecosystem enzyme C:N:P stoichiometric ratio (1:1:1). The enzyme C:N increased, whereas the enzyme N:P decreased, with increasing stand age, and both ratios tended to be stable after 17 a. There was no significant difference in enzyme N:P among different stand ages. The vector length of enzyme stoichiometry was not significantly different among the five stand ages. The vector angles increased with the increase in stand ages and tended to be stable after 17 a of stand age, but the angles were less than 45°. Redundancy analysis (RDA) revealed that soil carbon quality index and pH were the main factors influencing soil enzyme activity and the associated stoichiometric ratio. Our findings indicated that P. massoniana plantation soil microorganisms at different growth stages were all subjected to N limitation, and the N limitation was alleviated with the increase in stand age; however, the P requirement was gradually enhanced. Therefore, the management of P. massoniana plantations should take care to increase nitrogen fertilizer at the early growth stage of P. massoniana, and more phosphorus fertilizers need to be applied with nitrogen at the late growth stage in order to maintain the productivity and sustainable development of P. massoniana plantations.

[Evaluation of insulin resistance in type 1 diabetes with euglycemic-hyperinsulinemic clamp].

OBJECTIVE: To investigate insulin resistance in type 1 diabetes (T1DM) with euglycemic-hyperinsulinemic clamp. METHODS: Eight cases of newly diagnosed T1DM and 8 cases of newly diagnosed type 2 diabetes (T2DM) were selected. Their insulin sensitivity index (ISI) was evaluated with euglycemic-hyperinsulinemic clamp after 2 week insulin intensive treatment and compared with that of 10 healthy volunteers (normal control group, NC group). RESULTS: Age, BMI, fasting insulin (FIns), fasting C-peptide in the T1DM group were significantly lower than those in the NC group, while waist-to-hip ratio (WHR), systolic blood pressure (SBP), diastolic blood pressure (DBP), TC, TG, LDL-C, HDL-C were not significantly different between the T1DM and NC groups. Age, BMI, WHR, FIns, fasting C-peptide, SBP, TC, TG in the T1DM group were significantly lower than those in the T2DM group. The ISI of the NC, T1DM and T2DM groups were 12. 83 +/- 1.09, 9.95 +/-0.50, 3.80 +/- 0.20, respectively. There was significant difference among the three groups (P < 0.05). CONCLUSION: The ISI in T1DM was significantly lower than that in NC group, but higher than that in T2DM.

[Evaluation of insulin secretion and insulin resistance by hyperglycemic clamp in Graves disease patients with impaired glucose tolerance].

OBJECTIVE: To investigate the state of insulin secretion and insulin resistance in patients of Graves disease (GD) with impaired glucose tolerance (IGT) by hyperglycemic clamp. METHODS: Six cases of Graves disease with IGT were selected as GD + IGT group and ten healthy volunteers as normal control group (NC group). All the subjects were required to fast for 12 hours and then underwent hyperglycemic clamp to assay insulin secretion and insulin sensitivity. Glutamic acid decarboxylase antibody (GAD-A) was tested in all the subjects. RESULTS: Insulin secretion in GD + IGT group was significantly higher than that in NC group. The 1st phase insulin secretion (1PH) was (636.31 +/- 105.54) mIU/L vs (233.56 +/- 21.33) mIU/L, P = 0.001. The 2nd phase insulin secretion (2PH) was (146.68 +/- 25.00) mIU/L vs (67.06 +/- 6.23) mIU/L, P = 0.03. The maximal insulin secretion during 120 - 150 minutes (Ins(120 - 150)) was (195.05 +/- 32.94) mIU/L vs (87.64 +/- 9.78) mIU/L, P = 0.04. The hyperglycemic clamp insulin sensitivity index (average glucose metabolic rate during 120 - 150 minutes/Ins(120 - 150)) was significantly lower in GD + IGT group than that in NC group (11.52 +/- 1.90 vs 21.72 +/- 3.25, P = 0.04). GAD-A was negative in all subjects. CONCLUSION: Cases of GD with IGT show significant insulin resistance with compensated elevated insulin secretion.