To enhance in vitro dissolution of Cur by preparing Cur solid dispersions. The ability of HPMCAS-HF,HPMCAS-MF,HPMCAS-LF and PVPK30 to maintain supersaturated solution was investigated by supersaturation test. Amorphous solid dispersions were prepared by the solvent-evaporation method. The prepared samples were characterized using infrared spectroscopy( IR) and differential scanning calorimetry( DSC),and in vitro dissolution was investigated. DSC and IR results showed that in 1 ∶3 and 1 ∶9 solid dispersions,Cur was amorphously dispersed in the carrier,and the interaction existed between drug and carrier. The supersaturation test showed that the order of the ability of polymer to inhibit crystallization of Cur was MF>HF>LF>K30. The dissolution results showed that Cur-K30 amorphous solid dispersion had the highest drug release rate; Cur-K30 and Cur-LF amorphous solid dispersions had a quicker but not stable dissolution rate,and the drug concentration decrease after 4 h; Cur-MF and Cur-HF solid dispersions had a low dissolution,which however increased steadily,attributing to the strong ability of the polymers to inhibit the crystallization of Cur. HPMCAS could inhibit the degradation of Cur better than K30,especially MF and HF. The amorphous solid dispersions of cur significantly enhanced the dissolution of Cur and improved the chemical stability of Cur. This study can provide a basis for the rational selection of the polymer used for Cur solid dispersion.
Chemistry, Pharmaceutical ; Curcumin ; chemistry ; Drug Stability ; Methylcellulose ; analogs & derivatives ; chemistry ; Polymers ; Solubility

Objective To investigate the effect of magnesium sulfate on NF-κB p65,inflammatory cyto-kines in brain and serum of preeclampsia model rats by magnesium sulfate. Methods The healthy SD rats were randomly divided into 4 groups,normal pregnancy group(n = 10),magnesium sulfate control group(n = 10), preeclampsia(PE)model group(n = 10)and magnesium sulfate intervention group(n = 10). Blood pressure, urinary protein,blood urea nitrogen and alanine aminotransferase levels were detected in rats in each group. RT-qP-CR and ELISA were used to detect the expression of IL-1β,TNF-αand IL-6 in the brain and serum. Western blot assay was used to detect the expression of the NF-κB p65 in brain. Results The level of proteinuria,blood urea nitrogen and blood pressure in PE model rats were significantly higher than those in the normal pregnancy group and those in the magnesium sulfate intervention group at 20 days of gestation(P<0.05). Results of RT-qPCR and ELISA assay showed that IL-1β,TNF-α and IL-6 level in magnesium sulfate intervention group were sig-nificantly lower than those in PE model group(P<0.05),but still higher than those in the normal pregnancy group (P < 0.05). Western blot result showed that NF-κB p65 in the magnesium sulfate intervention group was lower than that in the PE group(P<0.05),but still higher than that in the normal pregnancy group(P<0.05). Con-clusion The prevention and treatment preeclampsia mechanism of magnesium sulfate may inhibit inflammatory cyto-kines through NF-κB p65 pathway in the preeclampsia model rats.

AIM:To evaluate the agreement of corneal high-order aberrations from Topcon KR-1W, i.Profiler and OPD-Scan Ⅲ wavefront aberrometers in myopic adults.METHODS:A prospective clinical study. A total of 92 adult patients(92 eyes)with myopia in the department of optometry, the People's Hospital of Guangxi Zhuang Autonomous Region from June to August 2022 were enrolled. The third-order and fourth-order corneal aberrations at the pupil diameter of 4 and 6mm were measured by Topcon KR-1W, i.Profiler, and OPD-Scan Ⅲ, respectively. The difference and agreement of the three aberrometers were evaluated.RESULTS: The measurements at 6mm pupil diameter were all greater than those at 4mm pupil diameter. Although there were no statistical differences in the measurements of Z-44、Z-24 by the three aberrometers at 4 pupil diameter(P>0.05), there were statistical differences in other measurements(P<0.05). The aberration results measured by the three aberrometers were statistically different at the 6mm pupil diameter(P<0.05). The 95% limit of agreement(95%LoA)of the measurements of higher-order aberration, including the third-order aberrations at 4mm pupil diameter and the third-order and fourth-order aberrations at 6mm pupil diameter(except for the Z-24)were greater than 0.1μm. The concordance correlation coefficient(Pc)was lower than 0.90, indicating a poor consistency. The correlation coefficients of corneal higher-order aberrations were significantly different among the three aberrometers at 4 and 6mm pupil diameter(r4mm=0.215～0.805, P4mm<0.05; r6mm=0.561～0.916, P6mm<0.001).CONCLUSION:There were significant differences in the measurements of the third- and fourth-order corneal aberrations at 4 and 6mm pupil diameter among Topcon KR-1W, i.Profiler, and OPD-Scan Ⅲ, and the agreements were poor, so they are not interchangeably in clinical applications.

AIM: To study the subfoveal choroidal thickness(SFCT)and its influencing factors in children with different degree of myopia.

METHODS: This is prospective cohort study. Eighty-nine eyes of 45 school-age children aged 5-14 years old were studied, and according to the equivalent sphericity(SE)into different refractive groups. Mild, moderate and high myopia groups had 27, 42 and 20 eyes respectively, apply the enhanced depth scanning mode(EDI-OCT)of an optical coherence tomography(OCT)scanner to measure SFCT to compare choroid thickness differences among myopia groups, to find out the change rule of SFCT between myopia groups, and Pearson correlation analysis was used to analyze the related influencing factors.

RESULTS:SFCT of mild myopia, moderate myopia and high myopia respectively were(253.22±43.56)μm,(223.19±54.93)μm,(185.90±50.99)μm, SFCT differences between different refractive groups were statistically significant(P<0.05), Pearson correlation analysis found that there was a significant correlation between SFCT and SE and axial length(r=0.430, -0.499, 0.425, all P<0.001); slightly related to K1 and K2, and the correlation of AL, retinal nerve fiber layer(RNFL)thickness were better than that of SE. There were statistically significant differences in family history of myopia among the myopic groups(χ2=7.44, P<0.05).

CONCLUSION: The degree of myopia in children was deepened and SFCT became thinner. The degree of myopia in children is related to the family history of myopia.

Seventeen compounds were isolated from the 95% ethanol extract of the stems and leaves of Sapium discolor by using various chromatographic techniques,including silica gel,Sephadex LH-20,MCI,ODS,and semi-preparative HPLC. Their structures were elucidated as sapiumin F( 1),kadsulignan C( 2),ciwujiatone( 3),ethylbrevifolin carboxylate( 4),7-hydroxy-8-methoxycoumarin( 5),fraxetin( 6),fraxidin( 7),isofraxidin( 8),6,7,8-trimethoxycoumarin( 9),5,6,7,8-tetramethoxycoumarin( 10),8-hydroxy-5,6,7-trimethoxycoumarin( 11),3,3'-di-O-methylellagic acid( 12),3,3',4'-tri-O-methylellagic acid( 13),3'-methoxyellagic acid 4'-O-α-rhamnopyranoside( 14),4,5-didehydro-chebulic acid triethyl ester( 15),ent-kaurane-3-oxo-16α,17-diol( 16),and abscisic acid( 17) by spectroscopic data. Compound 1 is a new compound. Except for compounds 4,11,and 13,the remaining compounds were isolated from this plant for the first time. All the isolates were evaluated for their in vitro antineuroinflammatory activities,and the results showed that compounds 6 and 15 significantly inhibited nitric oxide production in lipopolysaccharide-induced BV-2 microglial cells,with IC50 values of 6. 06 and 6. 05 μmol·L-1,respectively.
Animals ; Cell Line ; Chromatography, High Pressure Liquid ; Mice ; Phytochemicals ; analysis ; Plant Leaves ; chemistry ; Plant Stems ; chemistry ; Sapium ; chemistry

Objective To investigate the effects of mechanical strain on Ca-calmodulin dependent kinase (CaMK)-cAMP response element binding protein (CREB) signal pathway and proliferation of osteoblasts.Methods Using a four-point bending device, MC3T3-E1 cells were exposed to mechanical tensile strains of 2500 µs and 5000 µs at 0.5 Hz respectively. The intracellular free Ca([Ca]i) concentration and calmodulin activity were assayed by fluorospectrophotometry, CaMK II β, CREB, and phosphorylated (activated) CREB (p-CREB) were assessed by Western blot, and cells proliferation was assayed with MTT. Pretreatment with verapamil was carried out to block Cachannel, and inhibitor U73122 was used to inhibit phospholipase C (PLC).Results Mechanical strains of 2500 µs and 5000 µs for 1 to 10 minutes both increased [Ca]i level of the cells. The 2500 µs strain, a periodicity of 1 h/d for 3 days, activated calmodulin, elevated protein levels of CaMK II β and p-CREB, and promoted cells proliferation, which were attenuated by pretreatment of verapamil or U73122. The effects of 5000 µs strain on calmodulin, CaMK II β, p-CREB and proliferation were contrary to 2500 µs strain.Conclusion The mechanical strain regulates osteoblasts proliferation through Ca-CaMK-CREB signal pathway via Cachannel and PLC/IPtransduction cascades.

Objective: To investigate the effect of niacinamide mononucleotide (NMN) on the fibrosis of renal cells in the rats with diabetic nephropathy (DN), and to elucidate the mechanism of NMN in regulating the fibrosis of renal parenchymal cells through silent information regulator 1 (Sirtl) and AKT pathways. Methods: The rat models of type 2 diabetes mellitus were induced by streptozotocin (STZ) and the model rats were randomly divided into experiment group (n= 30) and control group (n=10). The rats in experiment group were divided into diabetes + NMN group (n=15) and diabetes + PBS group (n=15). The rats in diabetes+ NMN group were given subcutaneous injection of NMN for 20 d and the rats in diabetes + PBS group were given 200 μL sterile PBS in the same way. Then the rats were decapitated and the kidney tissues were taken for section and protein extraction. The expression levels of Sirtl, AKT, p-Fox03a and Cav-1 proteins in kidney tissue of the rats in various groups were detected by Western blotting method and immuno-confocal focusing. The glomerular mesangial HBZY-1 cells were treated with high concentration of glucose (200 mmol · L-1) for 3-6 d, and then the cells were further randomly divided into 4 groups (treated with 0, 50, 100, and 200 mmol · L-1 NMN) and the cells only treated with 5. 6 mmol · L-1 glucose were regareded as control group. After 24 h culture, the cells were collected and the expression levels of Sirtl, AKT, and p-Fox03a proteins in the HBZY-1 cells in various groups were detected by Western blotting method. Results: Compared with diabetes +PBS group, the expression levels of Sirtl and AKT proteins in the renal parenchyma cells of the rats in diabetes+ NMN group were significantly increased (P<0. 01) and the expression levels of p-Fox03a and Cav-1 proteins in the renal parenchyma cells of the rats in diabetes + NMN group were also increased (P<0. 01). Compared with control group, the expression levels of Sirtl and AKT proteins in the HBZY-1 cells of the rats in 50 mmol · L-1 NMN group were significantly increased (P<0. 01), and the expression levels of Sirtl, AKT, and p-Fox03a proteins in the HBZY-1 cells in 100 and 200 mmol · L-1 NMN groups were increased significantly (P<0. 05 or P<0. 01). Conclusion: NMN can increase the expression levels of endogenous p-Fox03a and Cav-1 proteins in the glomerular cells of the DN rats by regulating the expression levels of Sirtl and AKT proteins, indicating that NMN and its analogues may play an important role in the prevention and treatment of the renal fibrosis of the DN rats.

Objective To observe the effects of interleukin-1β (IL-1β) and pentylenetetrazol (PTZ) induced acute epilepsy and the dynamic expression of aquaporin-4 (AQP4) in hippocampus. To explore the role of IL-1β in the pathogenesis of epilepsy by regulating AQP4. Methods All rats were randomly divided into control group, IL-1β group, PTZ group, IL-1ra + PTZ group and dexamethasone + PTZ group. Observe the behavior of the rats within 60 minutes after injection and record seizure score in each group. Then immunohistochemistry and RT-qPCR were used to detect the expression of AQP4 at at 6 , 12, 24 and 36 h. Results Almost of rats in IL-1β group and PTZ group showed severe degree seizure. The rats in control group and dexamethasone + PTZ group showed no obvious seizure. The seizure of rats were more remarkable serious in PTZ group than that in the IL-1ra + pentylenetetrazole group (P < 0.05). Immunohistochemistry and RT-qPCR Show: the expression of AQP4 in hippocampus in PTZ group increased gradually after 12 h (P < 0.05), then reached in the peak after 24 h (P < 0.001). The expression of AQP4 in IL-1ra + PTZ group was lower compare with PTZ group in each time (P < 0.05). Although the expression of AQP4 in dexamethasone + PTZ group higher than the control group, it was not significantly different (P < 0.05). Conclusion The proinflammatory cytokine IL-1β break the balance of water in brain and increasing the concentration of extracellular excitatory amino acids or ions by upregulate the expression of AQP4 in order to promote the excitatory of neurons.

Gram-positive bacteria secrete virulence factors into host cells and cause suppurative inflammation, which leads to the emergence of diseases, therefore poses a great threat to human health. Identifying secreted proteins is beneficial to understand the secretion system and pathogenic mechanism of bacteria, and lays the foundation for further screening of pathogenic factors. Due to the lack of classical signal peptide sequence in non-classical secreted proteins, it is relatively difficult and time-consuming to identify such proteins in large-scale experiments. At present, some computational prediction methods have been proposed, but their performance in predicting non-classical secreted proteins of Gram-positive bacteria is not satisfactory. This paper proposed an ensemble learning model - SPNG+, which integrates six machine learning algorithms including naive bayes, random forest, support vector machine, two gradient promotion trees XGBoost and LightGBM, and K-nearest neighbor through stacking strategy. The results of 5-fold cross validation and independent dataset test show that the SPNG+ is superior to the single machine learning model, the simple integrated learning model and the existing prediction tools in predicting non-classical secreted proteins of Gram-positive bacteria. Compared with the predictors constructed by limited feature coding methods or single machine learning algorithms in the past, the proposed method is a useful supplement to the study of non-classical secreted proteins in Gram-positive bacteria. The source code of SPNG+ is available from https: / / github.com / weidai00 / SPNG.

OBJECTIVE: To explore the molecular mechanism of fibroblast growth factor 8b (FGF8b) in promoting epithelial-mesenchymal transition in prostate cancer DU145 cells. METHODS: Cells were selected in three groups as follows: a block control group (DU145 cells), a negative control group [DU145 cells transfected with empty plasmid (pcDNA3.1/DU145)], and an experimental group [DU145 cells transfected with FGF8b (FGF8b/DU145)]. The activity of extracellular regulated protein kinases1/2( ERK1/2) pathway was detected by western-blot in the three groups. The FGF8b-DU145 cells and DU145 cells were cultured with PD98059 (an ERK kinase inhibitor) to observe microscopically the morphology changes within the cells. The experimental samples were also divided into four groups: FGF8b/DU145 cells cultured with 2% FBS (Group A); FGF8b/DU145 cells cultured with 2% FBS+PD98059 (50 μmol/L) (Group B); DU145 cells cultured with 2% FBS (Group C); DU145 cells cultured with FBS+PD98059 (50 μmol/L) (Group D). The expression of epithelial- mesenchymal transition (EMT) markers (E-cadherin, vimentin) were detected by western-blot analysis and the cell's mobility were detected by the Transwell chamber. RESULTS: The activity of ERK1/2 in the experimental group was significantly higher than that in the other two control groups; when ERK kinase inhibitor PD98059 was added to FGF8b/ DU145 cells, the expression of epithelial marker E-cadherin protein was significantly increased in group B compared with that in the group A (P<0.05). The expression of mesenchymal marker vimentin protein was significantly reduced in group B compared with that in group A (P<0.05). The cell migration assay suggested that cell migration was markedly decreased in group B (P<0.05) compared with that in group A. CONCLUSION EMT in prostate cancer induced by FGF8b can be mediated by ERK kinase pathway, in which mitogen-activated/extraceluer signal regulated kinase 1 (MEK1) may be a key factor. MEK1 could be an effective target in regulating the invasion and migration of prostate cancer.
Epithelial-Mesenchymal Transition ; genetics ; Fibroblast Growth Factor 8 ; genetics ; metabolism ; Flavonoids ; pharmacology ; Humans ; MAP Kinase Kinase 1 ; metabolism ; MAP Kinase Signaling System ; physiology ; Male ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Prostatic Neoplasms ; genetics ; metabolism ; pathology ; Transfection ; Tumor Cells, Cultured