FKBP11 promotes cell proliferation and tumorigenesis via p53-related pathways in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is one of the causes of cancer-related death worldwide. The abnormal proliferation ability of OSCC has become one of the major reasons for its poor prognosis. FK-506 binding protein 11 (FKBP11) is abnormally expressed in malignant tumors and affects many biological processes. The purpose of this study is to investigate the effect of FKBP11 on cell proliferation in OSCC and explore the possible regulatory mechanism. The expression of FKBP11 was detected by western blotting (WB) and/or real-time PCR in OSCC and paracancerous normal tissues in tongue squamous cell carcinoma (TSCC) cell lines, revealing high expression in OSCC and CAL-27 cells. Furthermore, FKBP11 knockdown inhibited the proliferation of CAL-27 cells by CCK-8 and colony formation assays. G2/M arrest and induction of apoptosis were observed using flow cytometry, Hoechst 33258 and Calcein-AM/PI staining, accompanied by changes in some cell cycle- and apoptosis-related proteins, including CDK1, Cyclin B1, p21, p27, p53, Bax, Bcl-2 and Caspase-3. Additionally, the expression of these proteins can be reversed by the use of pifithrin-α (PFT-α), a p53 inhibitor. An in vivo xenograft model further confirmed that FKBP11 enhanced OSCC progression. In conclusion, FKBP11 could promote cell proliferation by regulating G2/M phase and apoptosis via the p53/p21/p27 and p53/Bcl-2/Bax pathways, respectively, which suggests that it may be a new candidate target for the treatment of OSCC.

Fabrication of Metal-Organic Framework MOF-177 Coatings on Stainless Steel Fibers for Head-Space Solid-Phase Microextraction of Phenols.

Direct head-space solid-phase microextraction (HS-SPME) of phenols in water is usually difficult due to its polarity and solubility in aqueous matrix. Herein we report the fabrication of metal-organic framework MOF-177 coated stainless steel fiber for the HS-SPME of phenols (2-methylolphenol, 4-methylolphenol, 2,4-dimethylolphenol, 2,4-dichlorphenol, and 3-methyl-4-chlorophenol) in environmental water samples prior to the gas chromatography-mass spectrometry detection. Several parameters affecting the extraction efficiency were optimized in the experiment, including extraction temperature and time, the pH value and salt addition. The results indicated that the coated fiber gave low detection limits (0.015-0.043 µg L-1) and good repeatability with the RSD ranging from 2.8% to 5.5% for phenols. The recoveries are between 84.5%-98.6% with the spiked level of 10 µg L-1 for the real water samples. The established method may afford a kind of potential enrichment material and a reference method for the analysis of methylphenols in water samples.

Synthesis and biological evaluation of new pleuromutilin derivatives as antibacterial agents.

Several pleuromutilin derivatives possessing thiadiazole moieties were synthesized via acylation reactions under mild conditions. The in vitro antibacterial activities of the derivatives against methicillin-resistant S. aureus, methicillin-resistant S. epidermidis, S. aureus, S. epidermidis, E. coli, and B. cereus were tested by the agar dilution method and Oxford cup assay. All the screened compounds displayed potent activity. Compound 6d was the most active antibacterial agent because of its lowest MIC value and largest inhibition zone. Docking experiments were performed to understand the possible mode of the interactions between the derivatives and 50S ribosomal subunit. Moreover, the absorption, distribution, metabolism, excretion and toxicity properties of the synthesized compounds were analyzed after prediction using the Advanced Chemistry Development/Percepta Platform available online.

A fourfold interpenetrating diamondoid three-dimensional coordination polymer: poly[[[µ2-1,2-bis(pyridin-4-yl)ethene-κ2N:N'](µ2-5-hydroxyisophthalato-κ2O1:O3)zinc(II)] 1,2-bis(pyridin-4-yl)ethene hemisolvate].

In the title compound, {[Zn(C8H4O5)(C12H10N2)]·0.5C12H10N2}n or {[Zn(HO-BDC)(bpe)]·0.5bpe}n [HO-H2BDC is 5-hydroxyisophthalic acid and bpe is 1,2-bis(pyridin-4-yl)ethene], the asymmetric unit contains a Zn(II) atom, one HO-BDC ligand, one coordinated bpe ligand and half a noncoordinating bpe molecule with crystallographic inversion symmetry. Each Zn(II) centre is four-coordinated by two O atoms from two distinct HO-BDC ligands and two N atoms from two different bpe ligands in a ZnO2N2 coordination environment. The three-dimensional topology of the title compound corresponds to a fourfold interpenetrating diamondoid coordination polymer network, with the uncoordinated bpe ligands located in the cavities, hydrogen bonded to the main network via the hydroxy group of the HO-H2BDC ligand.

A two-dimensional network containing an -Mn-O-C-O-Mn- chain: poly[diaqua[1,2-bis(pyridin-4-yl)ethylene][µ3-3-carboxy-5-(carboxylatomethoxy)benzoato]manganese(II)].

In the title compound, [Mn(C10H6O7)(C12H10N2)(H2O)2]n or [Mn(HOABDC)(bpe)(H2O)2]n [H3OABDC is 5-(carboxymethoxy)isophthalic acid and bpe is 1,2-bis(pyridin-4-yl)ethylene], each Mn(II) cation is at the centre of a distorted octahedron formed by three carboxylate O atoms from three different HOABDC(2-) ligands, one pyridyl N atom from the terminal bpe ligand and two water molecules. The flexible oxyacetate group bound to a methylene C atom of the HOABDC(2-) ligand links the Mn(II) centres into -Mn-O-C-O-Mn- chains, and the carboxylate group bound directly to the benzene ring extends the chains into two-dimensional layers which lie parallel to the (010) plane and present herringbone patterns. Intermolecular O-H...N and C-H...O hydrogen bonds connect the layers into a three-dimensional supramolecular structure.

Effect of acidic culture conditions on the proliferation, apoptosis, and migration ability of human tongue squamous cell carcinoma cells and its related mechanism.

OBJECTIVES: This study aims to explore the effect of acidic culture conditions on the proliferation, apoptosis, and migration ability of human tongue squamous cell carcinoma SCC15 and CAL27 cells and its potential molecular mechanism. METHODS: After acidic culture for different periods, methyl thiazolyl tetrazolium (MTT) method was adop-ted to detect the cell proliferation of SCC15 and CAL27. Flow cytometry was employed to detect the apoptosis level of SCC15 and CAL27 cells. The migration ability of SCC15 and CAL27 after acidic culture was detected by scratch hea-ling test. Real-time fluorescence quantitative polymerase chain reaction (FQ-PCR) was used to detect the mRNA expression of cyclooxygenase 2 (COX-2) and survivin in SCC15 and CAL27 cells after acidic culture. RESULTS: After culture for 24 h under acidic microenvironment, SCC15 and CAL27 cells grew rapidly and reached the stationary phase after adjustment for 3 days. The apoptosis levels of SCC15 and CAL27 cells decreased after acidic culture, but the most significant reduction occurred after 6 h of acidic culture. The scratch healing rates of SCC15 and CAL27 cells increased after acidic culture. The results of FQ-PCR showed that the mRNA expression levels of COX-2 and survivin in SCC15 and CAL27 cells increased after acidic culture. CONCLUSIONS: Extracellular acidic microenvironment can inhibit the apoptosis of tongue squamous carcinoma cells, promote their migration, and induce more adaptable and malignant tongue squamous carcinoma cells. The mechanism may be related to COX-2 and survivin and their signal pathways.

N,N-Bis(2-pyridylmeth-yl)aniline.

In the title compound, C(18)H(17)N(3), the two pyridyl rings make a dihedral angle of 54.55 (13)°. The dihedral angles between the phenyl ring and the two pyridyl rings are 73.61 (13) and 81.40 (13)°. In the crystal, weak inter-molecular C-H⋯π inter-actions are observed.

catena-Poly[[dichloridozinc(II)]-µ-1,1'-(butane-1,4-di-yl)diimidazole-κN:N].

The title compound, [ZnCl(2)(C(10)H(14)N(4))](n), is a coordination polymer consisting of zigzag chains propagating in [001], in which the metal cation exhibits a distorted tetrahedral ZnCl(2)N(2) coordination. Adjacent chains are linked by inter-molecular C-H⋯Cl hydrogen bonds, forming a three-dimensional supra-molecular network.

An integrated strategy for revealing the pharmacological changes based on metabolites profiling and network pharmacology: Arctiin as an example.

Traditional Chinese medicine was widely used in China since its definite effects and therapy. The components of TCM were absorbed into the circle system as the format of prototypes or metabolites, which contributed to the therapy or side effects. Declaring the functional changes in this process was of great importance to the clinical applications. In this work, an integrated strategy based on metabolites' profiling and network pharmacology was proposed for exploring the pharmacological changes of compounds in vivo. Arctiin, the main component in Fructus Arctii with various kinds of bioactivities, was used as an example. An ultra-performance liquid chromatography coupled with time-of-flight mass spectrometry and metabolynx™software was applied to characterize the metabolites of arctiin in rats at a dosage of 100 mg/kg; network pharmacology was applied to characterize the functional changes. As a result, fifty-three metabolites (32 in plasma, 40 in urine, 19 in bile, 20 in feces, 1 in brain, 12 in liver and 4 in lungs) were screened out and characterized, and 3 of them were unambitiously identified by comparison with standard substances. Among them, 38 metabolites were reported for the first time. It was found the major metabolic pathways of arctiin in rats were demethylation, lactone-opening and phase II conjugations with sulfate and glucuronide.It also confirmed that M14, M15, M18, M23, M22, M43 and M45 were the major circulating forms of arctiin in rats following oral administration. In addition to the above metabolic reactions, phase I reactions of hydrolysis, demethylation, dehydroxylation were also observed, and dehydrogenation were first revealed metabolic patterns of arctiin in rats. Meanwhile, in addition to the main targets of arctiin (MTOR, EGFR and MAPK14), its metabolites targeted additional 392 targets with additional functions of anti-hepatitis B or viral carcinogenesis (SRC, CAPS3, PIK3CA, CDK4, ESR1, MMP9 and ERBB2). The above results provided very important information for understanding the metabolism and functional changes of arctiinin vivo, and supporting data for further pharmacological evaluation. Our work also provided a newsight for elucidation of functional changes of TCMs in vivo.

Constructing mixed-metal coordination polymers from copper(II)-pyridinedicarboxylate metalloligands.

In the mixed-metal complex catena-poly[bis[diaquasilver(I)] [bis[aquacopper(II)]-mu(3)-pyridine-2,5-dicarboxylato-2':1:1'kappa(5)N,O(2):O(5):O(5),O(5')-mu-pyridine-2,5-dicarboxylato-2:1kappa(4)N,O(2):O(5),O(5')-disilver(I)-mu(3)-pyridine-2,5-dicarboxylato-1:1':2''kappa(5)O(5),O(5'):O(5):N,O(2)-mu-pyridine-2,5-dicarboxylato-1':2'''kappa(4)O(5),O(5'):N,O(2)] hexahydrate], {[Ag(H(2)O)(2)][AgCu(C(7)H(3)NO(4))(2)(H(2)O)].3H(2)O}(n), a square-pyramidal Cu(II) center is coordinated by two N atoms and two O atoms from two pyridine-2,5-dicarboxylate (2,5-pydc) ligands and a water molecule, forming a [Cu(2,5-pydc)(2)(H(2)O)](2-) metalloligand. One Ag(I) center is coordinated by five O atoms from three 2,5-pydc ligands and, as a result, the [Cu(2,5-pydc)(2)(H(2)O)](2-) metalloligands act as linkers in a unique mu(3)-mode connecting Ag(I) centers into a one-dimensional anionic double chain along the [101] direction. The other Ag(I) center is coordinated by two water molecules, forming an [Ag(H(2)O)(2)](+) cation. Four adjacent Ag(I) centers are associated by Ag...Ag interactions [3.126 (1) and 3.118 (1) A], producing a Z-shaped Ag(4) unit along the [010] direction and connecting the anionic chains into a two-dimensional layer structure. This study offers information for engineering mixed-metal complexes based on copper(II)-pyridinedicarboxylate metalloligands.

A polymorph of diaqua-bis(pyrazine-2-carboxyl-ato-κN,O)copper(II).

The title compound, [Cu(C(5)H(3)N(2)O(2))(2)(H(2)O)(2)], is a new polymorph of the previously reported compound [Klein et al. (1982 ▶). Inorg. Chem.21, 1891-1897]. The Cu(II) atom, lying on an inversion center, is coordinated by two N atoms and two O atoms from two pyrazine-2-carboxyl-ate ligands and by two water mol-ecules in a distorted octa-hedral geometry with the water mol-ecules occupying the axial sites. Inter-molecular O-H⋯O, O-H⋯N and C-H⋯O hydrogen bonds connect the complex mol-ecules into a two-dimensional layer parallel to (10), whereas the previously reported polymorph exhibits a three-dimensional hydrogen-bonded network.

catena-Poly[diammonium [diaqua-bis(pyridine-2,4-dicarboxyl-ato-κN,O)cuprate(II)] [[diaqua-copper(II)]-µ-pyridine-2,4-dicarboxyl-ato-κN,O:O-[tetra-aqua-cadmium(II)]-µ-pyridine-2,4-dicarboxyl-ato-κO:N,O] hexa-hydrate].

The title mixed-metal complex, {(NH(4))(2)[Cu(C(7)H(3)NO(4))(2)(H(2)O)(2)][CdCu(C(7)H(3)NO(4))(2)(H(2)O)(6)]·6H(2)O}(n), contains one octa-hedrally coordinated Cd(II) center and two octa-hedrally coordinated Cu(II) centers, each lying on an inversion center. The two Cu(II) atoms are each coordinated by two O atoms and two N atoms from two 2,4-pydc (2,4-H(2)pydc = pyridine-2,4-dicarboxylic acid) ligands in the equatorial plane and two water mol-ecules at the axial sites, thus producing two crystallographically independent [Cu(2,4-pydc)(2)(H(2)O)(2)](2-) metalloligands. One metalloligand exists as a discrete anion and the other connects the Cd(H(2)O)(4) units, forming a neutral chain. O-H⋯O and N-H⋯O hydrogen bonds connects the polymeric chains, complex anions, ammonium cations and uncoordinated water mol-ecules into a three-dimensional supra-molecular network.

[Observation of the clinical efficacy of the bone filling bag vertebroplasty for the treatment of osteoporotic vertebral compression fractures].

OBJECTIVE: To explore the clinical effects of bone filling bag vertebroplasty in treating osteoporotic vertebral compression fractures. METHODS: The clinical data of 127 patients (145 vertebrae) with osteoporotic vertebral compression fractures who corresponded the criteria of inclusion and exclusion from December 2015 to June 2017 were retrospectively analyzed. Responsible vertebral bodies were identified by clinical situation, X-rays, CT scan, MRI. Among them, 95 cases (110 vertebrae) were treated by percutaneons kyphoplasty (PKP group), there were 34 males (42 vertebrae) and 61 females (68 vertebrae), with an average age of (73.92±7.14) years, 47 thoracic vertebra (T8-T12) and 63 lumbar vertebra (L1-L5). Other 32 patients (35 vertebrae) were treated by bone filling bag vertebroplasty(bone filling bag vertebroplasty group). There were 11 males (12 vertebrae) and 21 females (23 vertebrae), with an average age of (71.56±7.89) years, 16 thoracic vertebra (T9-T12) and 19 lumbar vertebra(L1-L5). Postoperative pain after 3 days, vertebral body height, improvement of lumbar function were recorded and bone cement diffusion and leakage were observed by X-rays. RESULTS: All operations were successful and no complications were found. In bone filling bag vertebroplasty group, operation time was (31.75±4.99) min, postoperative VAS score at 3 days was(2.38±0.94) points, anterior and middle height of the vertebral body were(19.54±2.36) mm and (18.16±2.65) mm, respectively; ODI score was(25.19±5.49) points, all above items after operation were better than preoperation(P<0.01), but there was no significant difference between two groups(P>0.05). Bone cement was patchy, clumpy or slightly dispersed by X-rays at 3 days after operation, the leakage rate of bone cement in bone filling bag vertebroplasty group was 2.86%(1/35), while was 6.36%(18/110) in PKP group, all of them were "trailing sign", there was significant difference between two groups (P<0.05). CONCLUSIONS: The clinical effect of bone filling bag vertebroplasty in the treatment of osteoporotic vertebral compression fractures is similar to percutaneous kyphoplasty, it can effectively relieve the pain, restore part vertebral body height and obviously reduce the leakage rate, with safer, it is a simple, rapid and effective therapeutic method.

[Effects of different treatments on patients with osteoporotic fracture after percutaneous kyphoplasty].

OBJECTIVE: To evaluate effects of different treatments on patients with osteoporotic vertebral fracture after percutaneous kyphoplasty in pain and function. METHODS: From March 2010 to March 2012,138 patients (165 vertebrae) with thoracic and lumbar vertebral osteoporotic fracture were randomly divided into three groups (control group, treatment group and comprehensive group), 46 cases in each group, and all patients were treated by PKP. Control group were treated with calcium and calcitriol after operation, treatment group added salmon calcitonin see calcimar based on control group, comprehensive group added incrementality waist musculi dorsi function exercise based on treatment group. VAS, ODI scores and BMD before operation, 3 d, 2 weeks, 1 month, 6 months and 12 months after operation were detected and compared. RESULTS: All operation were performed successfully,38 cases (45 vertebrae) in control group, 36 cases (44 vertebrae) in treatment group and 40 cases (49 vertebrae) were obtained complete following up, there was no significant meaning in following time among three groups (P>0.05). Postoperative VAS and ODI scores at 3 d, 2 weeks and 1 month among three groups were lower than that of before operation (P<0.01). Compared with control group, postoperative VAS score at 3 d, 2 weeks and 1 month were decreasedin treatment group and comprehensive group, but there was no significant meaning in ODI scores (P>0.05). At 6 and 12 months after operation,there was no significant differences in VAS and ODI between control group and treatment group (P>0.05), while VAS score in comprehensive group decreased much than other two groups,decreased continuously (P<0.01). At 12 months after operation, BMD among three groups were increased more than preoperative,and BMD in comprehensive group was more obviously than that of in control and treatment group. CONCLUSION: PKP, an effective method for the treatment of thoracic and lumbar vertebral osteoporotic fracture, could improve short-term clinical effects by adding calcitonin with calcium supplements and activated vitamin D. Waist musculi dorsi function exercise could improve long-term clinical effects of PKP and improve quality of life.

[Distribution of rag genotypes of Porphyromonas gingivalis in patients with chronic periodontitis].

OBJECTIVE: To investigate the distribution of rag genotypes of Porphyromonas gingivalis (P. gingivalis) in chronic periodontitis patients. METHODS: Subgingival plaque samples were collected from 50 chronic periodontitis patients. The occurrence of P. gingivalis was determined by polymerase chain reaction (PCR) using 16S rDNA-specific primers. Distribution of rag genotypes was assessed in P. gingivalis positive samples by PCR. RESULTS: The occurrence of P. gingivalis was 70.7%, and the distribution of four rag genotypes among P. gingivalis positive samples was as follows: rag-1 60.4%; rag-2 23.6%; rag-3 44.3%; rag-4 15.1%, respectively. CONCLUSION: P.gingivalis with various rag genotypes was present in subgingival plaque samples from chronic periodontitis patients, and P. gingivalis with rag-1 and rag-3 were more predominant in chronic periodontitis patients, which may be associated with the development of periodontitis.

[The expression of rag-1 of Porphyromonas gingivalis in different periodontal inflamed conditions].

PURPOSE: To analyse the expression of rag-1 of Porphyromonas gingivalis (P.gingivalis) in different periodontal inflamed conditions. METHODS: 150 subgingival plaque samples were collected from chronic periodontitis patients. The presence of P.gingivalis and rag-1 was determined by PCR. mRNA level of rag-1 was assessed in P. gingivalis rag-1 positive samples by RT-PCR. RESULTS: The mRNA level of rag-1 was 1.19+/-0.06, 0.46+/-0.05 and 2.22+/-0.10(P<0.05) respectively at the mild, moderate and severe inflammation sites. CONCLUSION: mRNA level of rag-1 may be changed with the different clinical periodontal inflamed condition.

[Study on Porphyromonas gingivalis colonization in patients with periodontitis after periodontal initial therapy].

OBJECTIVE: To examine Porphyromonas gingivalis (Pg) in subgingival plaque of the patients with periodontitis and to find out the rules of Pg colonization after periodontal initial treatment. METHODS: A total of 1620 subgingival plaque samples were collected from 180 subjects including chronic periodontitis (CP) patients (n = 90), and aggressive periodontitis (AgP) patients (n = 90) in different periods of periodontal initial therapy-the baseline, 6 weeks, and 12 weeks after treatment. The following periodontal clinical parameters were recorded with Florida probe at sampled sites: probing depth (PD), clinical attachment loss (CAL), and bleeding on probing (BOP). Quantities of Pg were examined by AmpliFluor endpoint quantitative polymerase chain reaction. RESULTS: At the 6th week of periodontal initial therapy, there were 61 (22.6%) and 66 (24.4%) Pg increased sites respectively, in which no significant difference was detected (P > 0.05). At baseline of periodontal initial therapy, more severe periodontal clinical parameters of Pg increased sites were observed than those of Pg stationary sites. At the 12th week, however, there were 96 (35.6%) and 18 (6.7%) Pg increased sites respectively, significant difference detected (P < 0.05). At 6th week of periodontal initial therapy, more severe periodontal clinical parameters of Pg increased sites were observed than those of Pg stationary sites. CONCLUSIONS: Pg colonization in AgP and CP patients started 6 weeks after periodontal initial therapy, but the recolonization pattern was different between these two groups of patients. Severe periodontitis sites in baseline seemed to place them at risk of Pg colonization after periodontal initial therapy.

Tetraaqua(1,10-phenanthroline-kappa(2)N,N')cobalt(II) dinitrate: a hydrogen-bonded supramolecular network.

The structure of the title compound, [Co(C(12)H(8)N(2))(H(2)O)(4)](NO(3))(2), consists of tetraaqua(1,10-phenanthroline)cobalt(II) cations and nitrate anions. The Co atom is located on a twofold rotation axis and is coordinated by the two N atoms of a 1,10-phenanthroline ligand and four O atoms of water molecules. The cations and anions are linked by hydrogen-bond interactions into a three-dimensional supramolecular network.