Rational construction of a triphenylphosphine-modified tetra-nuclear Cu(I) coordinated cluster for enhanced chemodynamic therapy.

A triphenylphosphine-modified tetra-nuclear Cu(I) coordinated cluster was constructed for enhanced chemodynamic therapy (CDT) by increasing the number of metal centers. Once inside human bladder cancer (T24) cells, a larger amount of copper accumulated compared with the mono-nuclear Cu(I) complex; the additional copper could generate more •OH and then induce more obvious apoptosis via a Fenton-like reaction, thus further increasing the tumor inhibition effect and ultimately improving the CDT efficiency.

Hypoglycemic effect of insulin-loaded hydrogel-nanogel composite on streptozotocin-induced diabetic rats.

At present, how to increase insulin rapidly, availably and stably is still a conundrum in the treatment of diabetes mellitus. In vitro studies have shown that insulin can be released from hydrogel-nanogel composite according to the changes of glucose level. This study aimed to observe the glucose-lowering effects and evaluate the safety of the insulin-loaded hydrogel-nanogel composite in diabetic rats. We found that significant glycemic regulation could be observed up to 30 hours after subcutaneous injection, and the fasting blood glucose was reduced effectively. The result of an oral glucose tolerance test showed that the level of insulin expressed a stable increase from 0.5 hours to 3.5 hours, which led to a reduction of glucose with steady steps. Also, compared with Ins group, the Gel+Ins group showed slighter skin and pancreas damage, while the oxidative stress and inflammation response were similar to the normal control group. In conclusion, these results demonstrated that the glucose-lowering action of the insulin-loaded hydrogel-nanogel composite was superior to that of the regular insulin, and might thus become an insulin carrier in the future.

Blood Levels of Glycated Hemoglobin, D-Dimer, and Fibrinogen in Diabetic Retinopathy.

PURPOSE: This study aimed to describe the levels of glycated hemoglobin (HbA1c), D-dimer (D-D), and fibrinogen (FIB) in different types of diabetic retinopathy (DR). METHODS: A total of 61 patients with diabetes, who were treated in our department between November 2017 and May 2019, were selected. According to their non-mydriatic fundus photography and fundus angiography results, patients were divided into three groups, ie, the non-DR (NDR) group (n=23), the non-proliferative DR (NPDR) group (n=17), and the proliferative DR (PDR) group (n=21). A control group of 20 people who had tested negative for diabetes was also included. The levels of HbA1c, D-D, and FIB were measured and compared, respectively. RESULTS: The mean values of HbA1c were 6.8% (5.2%, 7.7%), 7.4% (5.8%, 9.0%), and 8.5% (6.3%, 9.7%) in the NDR, NPDR, and PDR groups, respectively. The control group values were 4.9% (4.1%, 5.8%). These results indicated a significant statistical difference between groups. The mean values of D-D were 0.39 ± 0.21 mg/L, 1.06 ± 0.54 mg/L, and 1.39 ± 0.59 mg/L in the NDR, NPDR, and PDR groups, respectively. The control group result was 0.36 ± 0.17 mg/L. The values of the NPDR and PDR groups were significantly higher than those of the NDR and control groups, and the value of the PDR group was significantly higher than that of the NPDR group, indicating a significant difference between the groups (P < 0.001). The mean values of FIB were 3.07 ± 0.42 g/L, 4.38 ± 0.54 g/L, and 4.46 ± 1.09 g/L in the NDR, NPDR, and PDR groups, respectively. The control group result was 2.97 ± 0.67 g/L. The difference between the groups was statistically significant (P < 0.05). CONCLUSION: Blood levels of HbA1c, D-D, and FIB in the PDR group were significantly higher than in the NPDR group.

Synthesis, structural characterization and antitumor activity of six rare earth metal complexes with 8-hydroxyquinoline derivatives.

The rare earth metal Gd(III), Yb(III), Lu(III), Eu(III), Tb(III) and Ho(III) complexes 1-6 with 2-((2-(pyridin-2-yl)hydrazono)methyl)quinolin-8-ol (H-L) as ligands were synthesized. The in vitro cytotoxicity assay indicated that the cytotoxicity of 1 was equivalent to cisplatin and higher than that of H-L and other complexes towards T24 tumor cells. The mechanism study indicated that 1 caused significant up-regulation of the proteins p27, p21 and p53 in T24 cells and cell cycle arrest in G2 phase. In addition, 1 induced effective T24 cells apoptosis via mitochondrial dysfunction pathway, which was indicated by changes in mitochondrial membrane potential (Δψ), reactive oxygen species (ROS), intracellular Ca2+ and the mitochondria-related proteins (including cytochrome C (Cyt C), B-cell lymphoma-2 (Bcl-2), Bcl-2-associated x (Bax) and apoptotic protease activating factor-1 (Apaf-1)). Moreover, 1 could activate caspase-3/8/9 in T24 cells. Therefore, complex 1 is a promising and potent anticancer drug candidate.

Neuropilin1 silencing impairs the proliferation and migration of cells in pancreatic cancer.

BACKGROUND: Neuropilin1 (NRP1) participates in cancer cell proliferation, migration, and metastasis as a multifunctional co-receptor by interacting with multiple signal pathways, but few studies have addressed the precise function of NRP1 in pancreatic cancer (PACA) cells. We aimed to study whether NRP1 gene silencing involved in the proliferation and migration of PACA cells in vitro. METHODS: A lentiviral vector expressing NRP1 shRNA was constructed and transfected into human PACA cells (CFPAC-1 and PANC-1). The expression of NRP1 protein and mRNA was detected by Western blot and quantitative real-time polymerase chain reaction (qRT-PCR) assay, respectively. CCK-8 assay, wound healing assay, and transwell assay were conducted to examine the effect of NRP1 silencing on cells proliferation and migration capability. RESULTS: Results of qRT-PCR and Western blot showed successfully established, stably transfected shRNA-NRP1 cells in PACA cells. The proliferation capacity of PACA cells in NRP1 shRNA group was lower significantly than that in the negative control (NC) group (P < .05). The invasion and migration capability of PACA cells in NRP1 shRNA group was lower significantly than that in the NC group (P < .01). CONCLUSIONS: NRP1-shRNA lentiviral interference vectors can effectively decrease NRP1 gene expression in PACA cells, thereby inhibiting cells proliferation and migration, which provides a basis for finding a valuable therapeutic target for PACA therapy.

Synthesis and in vitro antitumor activity evaluation of copper(II) complexes with 5-pyridin-2-yl-[1,3]dioxolo[4,5-g]isoquinoline derivatives.

Seven Cu(II) complexes with 5-pyridin-2-yl-[1,3]dioxolo[4,5-g]isoquinoline derivatives as ligands: [Cu2(L1)2Cl4] (1), [Cu(L2)Cl2] (2), [Cu(L1)(NO3)2] (3), [Cu(L2)(NO3)2] (4), [Cu(L3)Cl2] (5), [Cu(L3)Br2] (6) and [Cu(L3)(NO3)2] (7){L1=9-nitro-5-pyridin-2-yl-[1,3]dioxolo[4,5-g]isoquinoline, L2=4-nitro-5-pyridin-2-yl-[1,3]dioxolo[4,5-g]isoquinoline, L3=9-bromo-5-pyridin-2-yl-[1,3]dioxolo[4,5-g]isoquinoline}, were synthesized and characterized. Their in vitro anticancer activities against T-24, MGC-80-3, HeLa, Hep-G2, A549 and SK-OV-3 were evaluated. Compared with their corresponding ligands, most of these complexes exhibited enhanced anticancer activities in contrast to their corresponding ligands and copper salt. Among them, complexes 1 and 3 displayed selective cytotoxicity to HeLa cells comparing with normal liver cell HL-7702, with IC50 values of 5.03 ±â€¯1.20 µM and 10.05 ±â€¯0.52 µM, respectively. Complexes 1 and 3 inhibited telomerase activity by interacting with c-myc promoter elements, and therefore exerted their antitumor activity. Furthermore, complexes 1 and 3 could trigger cell apoptosis via disruption of mitochondrial pathway through notably increased reactive oxygen species (ROS) levels, loss of mitochondrial membrane potential (Δψm), increase of the cytochrome c and apaf-1, decrease of bcl-2, and activation of caspases 3/9. Complexes 1 and 3 exhibited enhanced cytotoxicity, presenting synergetic effect after the ligands coordinated to copper(II) center.

Identification of Two Transcriptional Activators MabZIP4/5 in Controlling Aroma Biosynthetic Genes during Banana Ripening.

The transcriptional regulation of aroma formation genes remains poorly understood in the banana. In this work, we found that the expressions of a subset of aroma biosynthetic genes including MaOMT1, MaMT1, MaGT1, MaBCAT1, MaACY1, MaAGT1, and BanAAT, as well as two bZIP genes, MabZIP4 and MabZIP5, were down-regulated when prestored at 7 °C compared to those prestored at 22 °C during the ripening process of banana. Furthermore, MabZIP4 and MabZIP5 were shown to be able to activate the transcription of these aroma biosynthetic genes. Importantly, MabZIP4 directly binds to BanAAT promoter, while MabZIP5 binds to the promoters of MaMT1, MaACY1, MaAGT1, and BanAAT via the G-box motif, implicating the diverse functional significances of MabZIPs in controlling aroma biosynthesis in banana. Overall, this work sheds new insights on the understanding of transcriptional regulatory mechanisms associated with aroma formation during banana ripening.

Synthesis, crystal structure, cytotoxicity and action mechanism of a Rh(iii) complex with 8-hydroxy-2-methylquinoline as a ligand.

A rhodium(iii) complex, [Rh(MQ)(DMSO)2Cl2] (1), with 8-hydroxy-2-methylquinoline as the ligand was synthesized and characterized. Complex 1 exhibited cytotoxicity against BEL-7404, Hep-G2, NCI-H460, T-24, and A549 cell lines with IC50 values in the micromolar range (6.52-17.86 µM). Various experiments on the Hep-G2 cells showed that complex 1 caused cell cycle arrest at the S phase, downregulation of cdc25 A, cyclin A, cyclin B and CDK2, and upregulation of p21, p27 and p53. Furthermore, cytotoxicity mechanism studies suggested that complex 1-induced apoptosis was achieved via disruption of the mitochondrial function, which led to a significant loss of the mitochondrial membrane potential, an increase in the cellular levels of reactive oxygen species, cytochrome c, and apaf-1, and a fluctuation of the intracellular Ca2+ concentration. Taken altogether, complex 1 can trigger cancer cell death by inducing apoptosis through a mitochondrial dysfunction pathway.

[Cut-off points of fasting fingertip capillary blood glucose for detecting both undiagnosed diabetes and pre-diabetes].

OBJECTIVE: To determine the efficient cut-off points of fasting fingertip blood glucose test for undiagnosed diabetes mellitus (DM), impaired glucose tolerance (IGT), and impaired fasting glucose (IFG) in community-based residents aged above 45 years old. METHODS: A cluster-randomized study was conducted from May 2008 to January 2009. A total of 3250 subjects aged above 45 years in two communities of Baoding city received questionnaire investigation and tested for fingertip blood glucose. Those subjects whose capillary blood glucose level ≥ 5.1 mmol/L were subjected to 75 g oral glucose tolerance test. Undiagnosed diabetes mellitus and pre-diabetes were identified by fasting plasma glucose and OGTT. In this study, the cut-off points of fasting capillary blood glucose for detecting undiagnosed diabetes and pre-diabetes were evaluated, using receiver operator characteristic curve (ROC). RESULTS: Of 1351 subjects that having had oral glucose tolerance test, 230 cases were diagnosed as diabetes mellitus (7.3%), 166 cases (5.2%) as IFG, and 204 (6.7%) as IGT under fasting capillary blood glucose as test variable and state variables according to the following criteria. (1) FPG≥7.0 mmol/L or/and 2hPG≥11.1 mmol/L (2) FPG<5.6 mmol/L (3) FPG<7.0 mmol/L and 7.8 mmol/L≤2hPG≤11.1 mmol/L, areas under three ROC curves were 0.905, 0.633 and 0.719, respectively. The cut-off values of screening for undiagnosed DM, IGT and IFG were 6.0 mmol/L, 5.7 mmol/L, and 5.7 mmol/L, respectively. When cut-off value of screening for undiagnosed DM was 6.0 mmol/L, the maximal sensitivity was 78.0% and specificity was 89.3%. But there were both lower sensitivity and specificity in screening for IFG and IGT according to the best predicting value (5.7 mmol/L) from the ROC curves (50.3% and 28.0% vs. 60.8% and 28.0%). CONCLUSION: Fasting capillary blood glucose with the lower cut-point of 6.0 mmol/L in screening for undiagnosed diabetes mellitus alone, was relatively reliable, whereas for both IFG and IGT the fasting fingertip blood glucose tests were fallible. It was convenient and could be used in screening the DM at the community level.

Diaqua-bis-(3-nitro-benzoato-κO)bis-[1H-5-(3-pyrid-yl)-3-(4-pyrid-yl)-1H-1,2,4-triazole-κN]cobalt(II) dihydrate.

In the centrosymmetric title compound, [Co(C(7)H(4)NO(4))(2)(C(12)H(9)N(5))(2)(H(2)O)(2)]·2H(2)O, the Co(II) atom, located on an inversion center, is coordinated by two N atoms [Co-N = 2.155 (3) Å] and four O atoms [Co-O = 2.099 (2)-2.117 (3) Å] in a distorted octa-hedral geometry. Inter-molecular N-H⋯O, O-H⋯N and O-H⋯O hydrogen bonds link the components into a three-dimensional supramolecular framework.

[Determination of contents of many kinds of metal elements in Phellodendron by ICP-AES].

Dry and wet methods were used to digest Phellodendron grown in Jinxiu Dayaoshan of Guangxi with a high-pressure jar and to prepare the samples. The contents of microelements Cu, Fe, Zn, Mn and Ni and macroelements K, Ca, Mg, Sr and Na in Phellodendron were determined by using ICP-AES. Meanwhile, the optimal digestion conditions were found: 7 mL of HNO3 +HClO4 +H2O2 (volume ratio 5 : 1 : 1) for 4 h. The work condition and the optical wavelength were selected. The RSD was found to be less than 5% and the recovery rates of all elements were within the range of 89.4%-113.1%. The determined results agree with the analytical demand, and also indicate that Phellodendron contains high contents of Cu, Fe, Zn and Mn microelements. It is important to assess the medicinal value and understand pharmacological action of Phellodendron by the determination of microelements in the Chinese medicine with ICP-AES.

[A case-control study on risk factors of type 2 diabetes mellitus related chronic complications in Baoding city].

OBJECTIVE: To recognize the main risk factors and to provide evidence for prevention and intervention of type 2 diabetes chronic complications. METHODS: A hospital-based frequency matched case-control study including 200 type 2 diabetes mellitus (T2DM) chronic complications cases and 200 controls without T2DM chronic complications was carried out in Baoding city. Relationships between factors and T2DM chronic complications were analyzed by non-conditional uni-variate and multivariate logistic regression methodologies. RESULTS: High C-reactive protein (CRP) (OR = 5.568), dyslipidemia (OR = 4.400), high blood urea nitrogen (BUN) (OR = 4.399), high low density lipoprotein-cholesterol (LDL-C) (OR = 3.594), time of hospitalization (OR = 2.612), grease food intake before developing DM (OR = 2.300), high HbA1c% (OR = 1.747), lack of exercise after the development of DM (OR = 1.672), duration of DM (OR = 1.509), mental stress (OR = 1.427), high-quality sleep (OR = 0.606), well control of blood glucose (OR = 0.517), well control of blood fat (OR = 0.299), insulin injections (OR = 0.155) etc. were all significantly associated with T2DM chronic complications. CONCLUSION: The main risk factors of T2DM chronic complications seemed to be related to high CRP, dyslipidemia, high BUN and high LDL-C. The main protective factors were insulin injections, well control of blood fat and blood glucose, good-quality of sleep, while the unique risk factors of cardiovascular disease seemed to be high LDL-C and mental stress. The unique risk factors of neuropathy were lack of exercise after developing DM and the amount of sweet food intake. The duration of DM appeared to be the common risk factor and the common protective factor on those three complications was insulin injection.

Tetra-aqua-bis(3,5-di-4-pyridyl-1H-1,2,4-triazolido)cadmium(II) dihydrate.

In the title compound, [Cd(C(12)H(8)N(5))(2)(H(2)O)(4)]·2H(2)O, the Cd(II) atom is located on an inversion center and is coordinated by the two N atoms [Cd-N = 2.278 (2) Å] and four O atoms [Cd-O = 2.304 (2)-2.322 (2) Å] in a distorted octa-hedral geometry. Inter-molecular O-H⋯O and O-H⋯N hydrogen bonds link the complex into a three-dimensional supra-molecular framework.

Tetra-aqua-bis[3-(3-pyrid-yl)-5-(4-pyrid-yl)-1,2,4-triazolido]nickel(II) dihydrate.

In the title compound, [Ni(C(12)H(8)N(5))(2)(H(2)O)(4)]·2H(2)O, the Ni(II) atom is coordinated by the two N atoms [Ni-N = 2.094 (3) Å] and four O atoms [Ni-O = 2.063 (3)-2.083 (2) Å] in a distorted octa-hedral geometry. The mol-ecule is centrosymmetric and the Ni(II) atom is located on an inversion center. Inter-molecular O-H⋯N and O-H⋯O hydrogen bonds link the complex into a three-dimensional supra-molecular framework.

Bis[2-(2-pyridylmethyl-eneamino)benzene-sulfonato-κN,N',O]cadmium(II) dihydrate.

The title complex, [Cd(Paba)(2)]·2H(2)O or [Cd(C(12)H(9)N(2)O(3)S)(2)]·2H(2)O, was synthesized by the reaction of the potassium salt of 2-(2-pyridylmethyl-eneamino)benzene-sulfonic acid (PabaK) with CdCl(2)·2.5H(2)O in methanol. The Cd(II) atom lies on a crystallographic twofold axis and is coordinated by four N atoms and two O atoms from two deprotonated tridentate 2-(2-pyridylmethyl-eneamino)benzene-sulfonate ligands in a slightly distorted octa-hedral environment. There are extensive hydrogen bonds of the type O-H⋯O between the uncoordinated water molecules and the sulfonate O atoms, through which the complex forms a layered structure parallel to (001).