Semi-automatic proximal humeral trabecular bone density assessment tool: technique application and clinical validation.

PURPOSE: This study aimed to apply a newly developed semi-automatic phantom-less QCT (PL-QCT) to measure proximal humerus trabecular bone density based on chest CT and verify its accuracy and precision. METHODS: Subcutaneous fat of the shoulder joint and trapezius muscle were used as calibration references for PL-QCT BMD measurement. A self-developed algorithm based on a convolution map was utilized in PL-QCT for semi-automatic BMD measurements. CT values of ROIs used in PL-QCT measurements were directly used for phantom-based quantitative computed tomography (PB-QCT) BMD assessment. The study included 376 proximal humerus for comparison between PB-QCT and PL-QCT. Two sports medicine doctors measured the proximal humerus with PB-QCT and PL-QCT without knowing each other's results. Among them, 100 proximal humerus were included in the inter-operative and intra-operative BMD measurements for evaluating the repeatability and reproducibility of PL-QCT and PB-QCT. RESULTS: A total of 188 patients with 376 shoulders were involved in this study. The consistency analysis indicated that the average bias between proximal humerus BMDs measured by PB-QCT and PL-QCT was 1.0 mg/cc (agreement range - 9.4 to 11.4; P > 0.05, no significant difference). Regression analysis between PB-QCT and PL-QCT indicated a good correlation (R-square is 0.9723). Short-term repeatability and reproducibility of proximal humerus BMDs measured by PB-QCT (CV: 5.10% and 3.41%) were slightly better than those of PL-QCT (CV: 6.17% and 5.64%). CONCLUSIONS: We evaluated the bone quality of the proximal humeral using chest CT through the semi-automatic PL-QCT system for the first time. Comparison between it and PB-QCT indicated that it could be a reliable shoulder BMD assessment tool with acceptable accuracy and precision. This study developed and verify a semi-automatic PL-QCT for assessment of proximal humeral bone density based on CT to assist in the assessment of proximal humeral osteoporosis and development of individualized treatment plans for shoulders.

Retraction Note: Glycol chitosan incorporated retinoic acid chlorochalcone (RACC) nanoparticles in the treatment of Osteosarcoma.

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s12944-020-01416-2.

Theoretical study on the gas adsorption capacity and selectivity of CPM-200-In/Mg and CPM-200-In/Mg-X (-X = -NH2, -OH, -N, -F).

The adsorption capacities of a heterometallic metal-organic framework (CPM-200-In/Mg) to VOCs (HCHO, C2H4, CH4, C2H2, C3H8, C2H6, C2H3Cl, C2H2Cl2, CH2Cl2 and CHCl3) and some inorganic gas molecules (HCN, SO2, NO, CO2, CO, H2S and NH3), as well as its selectivity in ternary mixture systems of natural gas and post-combustion flue gas are theoretically explored at the grand canonical Monte Carlo (GCMC) and density functional theory (DFT) levels. It is shown that CPM-200-In/Mg is suitable for the adsorption of VOCs, particularly for HCHO (up to 0.39 g g-1 at 298 K and 1 bar), and the adsorption capacities of some inorganic gas molecules such as SO2, H2S and CO2 match well with the sequence of their polarizability (SO2 > H2S > CO2). The large adsorption capacities of HCN and HCHO in the framework result from the strong interaction between adsorbates and metal centers, based on analyzing the radial distribution functions (RDF). Comparing C2H4 and CH4 molecules interacting with CPM-200-In/Mg by VDW interaction, we speculate that the high adsorption capacities of their chlorine derivatives in the framework could be due to the existence of halogen bonding or strong electrostatic and VDW interactions. It is found that the basic groups, including -NH2, -N and -OH, can effectively improve both the adsorption capacities and selectivity of CPM-200-In/Mg for harmful gases. Note that the adsorption capacity of CPM-200-In/Mg-NH2 (site 2) (245 cm3 g-1) for CO2 exceeded that of MOF-74-Mg (228 cm3 g-1) at 273 K and 1 bar and that for HCHO can reach 0.41 g g-1, which is almost twice that of 438-MOF and nearly 45 times of that in active carbon. Moreover, for natural gas mixtures, the decarburization and desulfurization abilities of CPM-200-In/Mg-NH2 (site 2) have exceeded those of the MOF-74 series, while for post-combustion flue gas mixtures, the desulfurization ability of CPM-200-In/Mg-NH2 (site 2) is still comparable to those of the MOF-74 series at 303 K and 4 MPa. We hope that the current theoretical study could guide experimental research in the future.

Early VEGF inhibition attenuates blood-brain barrier disruption in ischemic rat brains by regulating the expression of MMPs.

Vascular endothelial growth factor (VEGF) inhibition has been demonstrated to be an effective strategy in preserving the integrity of the blood-brain barrier (BBB) in patients with acute ischemic stroke. Loss of the BBB is the key event associated with morbidity and mortality in these patients. However, the underlying mechanisms remain poorly understood. In the present study, the effects of VEGF inhibition and the possible mechanism that underlies acute cerebral ischemia in rats was investigated. Following the induction of transient middle cerebral artery occlusion for a 90­min period, either an anti­VEGF neutralizing antibody (RB­222; 5 or 10 µg), or IgG (control), was administered by intracerebroventricular injection at 1 h following reperfusion. Functional outcomes, BBB leakage, brain edema, microvessel numbers and the relative protein levels of VEGF, matrix metalloproteinase (MMP)-2, MMP-9, occludin and collagen-IV were then determined using neurological assessments, Evans Blue staining, brain water content, CD31 staining and western blotting. Treatment with RB­222 at a dose of 5 and 10 µg significantly improved neurological functional outcomes and diminished infarct size, BBB leakage and brain edema compared with the MCAO and IgG groups at 24 h following reperfusion; 10 µg RB­222 was more effective than a 5 µg dose of the antibody. In addition, RB­222 reduced the number of immature microvessels, which subsequently attenuated BBB permeability. RB­222 significantly repressed VEGF expression as well as decreased MMP­2 and MMP­9 expression. However, it enhanced occludin and collagen­IV levels in the ischemic rat brain compared with the MCAO and IgG groups. Taken together, the results indicate that early inhibition of VEGF may have significant potential against cerebral ischemia, partly by regulating the expression of MMPs.

Demethyleneberberine alleviates inflammatory bowel disease in mice through regulating NF-κB signaling and T-helper cell homeostasis.

OBJECTIVE: The activation of NF-κB signaling and unbalance of T-helper (Th) cells have been reported to play a key role in the pathogenesis of colitis. Cortex Phellodendri Chinensis (CPC) is commonly used to treat inflammation and diarrhea. Demethyleneberberine (DMB), a component of CPC, was reported to treat alcoholic liver disease as a novel natural mitochondria-targeted antioxidant in our previous study. In this study, we investigated whether DMB could protect against dextran sulfate sodium (DSS)-induced inflammatory colitis in mice by regulation of NF-κB pathway and Th cells homeostatis. METHODS: Inflammatory colitis mice were induced by 3% DSS, and DMB were orally administered on the doses of 150 and 300 mg/kg. In vitro, DMB (10, 20, 40 µM) and N-acetyl cysteine (NAC, 5 mM) were co-cultured with RAW264.7 for 2 h prior to lipopolysaccharide (LPS) stimulation, and splenocytes from the mice were cultured ex vivo for 48 h for immune response test. RESULTS: In vivo, DMB significantly alleviated the weight loss and diminished myeloperoxidase (MPO) activity, while significantly reduced the production of pro-inflammatory cytokines, such as interleukin (IL)-6 and tumor necrosis factor-α (TNF-α), and inhibited the activation of NF-κB signaling pathway. Furthermore, DMB decreased interferon (IFN)-γ, increased IL-4 concentration in the mice splenocytes and the ratio of IgG1/IgG2a in the serum. In vitro, ROS production and pro-inflammation cytokines were markedly inhibited by DMB in RAW264.7 cell. CONCLUSIONS: Our findings revealed that DMB alleviated mice colitis and inhibited the inflammatory responses by inhibiting NF-κB pathway and regulating the balance of Th cells.

Glycol chitosan incorporated retinoic acid chlorochalcone (RACC) nanoparticles in the treatment of Osteosarcoma.

BACKGROUND: Osteosarcoma is the most common of all the bone malignancies and accounts for 30-80% of the primary skeletal sarcomas. The overall survival rate of patients with osteosarcoma is < 20% suggesting poor prognosis. METHODS: The present study demonstrates the effect of retinoic acid chlorochalcone (RACC) incorporated glycol chitosan (GC) nanoparticle transfection in osteosarcoma cells. MG-63 and Saos-2 osteosarcoma cells were transfected with various concentrations of RACC-incorporated GC nanoparticle for 24 h. The effect on cell proliferation, Ezh2 expression, apoptosis, cell cycle arrest, cell migration and invasiveness, Akt phosphorylation and local tumour growth and metastases were studied. RESULTS: MG-63 and Saos-2 osteosarcoma cells on RACC-incorporated GC nanoparticle transfection for 24 h showed a concentration-dependent inhibition of cell proliferation. Of the various concentrations of RACC tested, the effective concentration started from 5 µM with an IC50 of 20 µM. Wound healing assay also showed that RACC-incorporated GC nanoparticles inhibited migration of tumor cells more effectively compared to the parent RA. RACC transfection resulted in inhibition of cell proliferation, Ezh2 expression inhibition, apoptosis through mitochondrial pathway by decrease in membrane potential and release of cytochrome c and cell cycle arrest in the G0/G1 phase. The invasiveness of cells treated with 5 and 20 µM RACC was decreased by 49 and 76% respectively, compared to the control. RACC-treated mice showed significantly lower number of metastases compared to that in the control mice. CONCLUSIONS: Thus, RACC-incorporated glycol chitosan nanoparticle strategy can be promising for the treatment of osteosarcoma.

Increased whole blood viscosity is associated with silent cerebral infarction.

BACKGROUND: The presence of silent cerebral infarction (SCI) increases the risk of transient ischemia attack, symptomatic stroke, cardiovascular disease and dementia. Increased viscosity is associated with aging, obesity, carotid intima-media thickness, metabolic syndrome, hypertension, diabetes, ischemic heart disease, and stroke. AIMS: The purpose of the study was to assess the hemorheological parameters levels in SCI patients. METHODS: A cross-sectional study was conducted to evaluate the association between hemorheological parameters and SCI in 1487 subjects (868 men and 619 women) undergoing medical check-up. RESULTS: The participants with SCI had higher whole blood viscosity (WBV) levels at low shear rate than those without SCI (10.34 ± 1.77 mPa.s vs. 8.98 ± 0.88 mPa.s; P <  0.001). Moreover, the subjects with a high WBV had a higher prevalence of SCI. Logistic regression analysis revealed that a significant association of WBV levels with the risk of SCI after adjustment for confounding factors (OR: 2.025; 95% CI: 1.750-2.343; P <  0.001). CONCLUSIONS: Whole blood viscosity at low shear rate is a novel indicator for SCI regardless of classical cardiovascular risk factors. Early measurement of whole blood viscosity may be helpful to assess the risk of stroke.

Decreased serum bilirubin is associated with silent cerebral infarction.

OBJECTIVE: The presence of silent cerebral infarction (SCI) increases the risk of transient ischemia attack, symptomatic stroke, cardiovascular disease, and dementia. Total bilirubin (TB) levels were demonstrated to be decreased in carotid intima-media thickness, cardiovascular disease, stroke, and peripheral arterial disease. However, little information is available concerning the correlation between TB and SCI. APPROACH AND RESULTS: A cross-sectional study was conducted to evaluate the association between TB and SCI in 2865 subjects (1831 men and 1034 women) undergoing medical checkup. The participants with SCI had lower TB levels than those without SCI. The subjects with a low TB had a higher prevalence of SCI. Moreover, partial correlation showed that TB levels were tightly correlated with brachial-ankle pulse wave velocity after adjusting for confounding covariates (r=-0.149; P<0.001). Multivariate logistic regression analysis revealed that higher TB was associated with a lower risk of SCI (odds ratio, 0.925; 95% confidence interval, 0.897-0.954; P<0.001). CONCLUSIONS: TB is a novel biochemical indicator for SCI regardless of classical cardiovascular risk factors. Early measurement of TB may be useful to assess the risk of SCI.

Regulation of ASIC1 by Ca2+/calmodulin-dependent protein kinase II in human glioblastoma multiforme.

Recent studies have implicated the acid-sensing ion channel 1 (ASIC1), a proton-gated cation channel that belongs to the epithelial sodium channel (ENaC)/Degenerin family, plays an important role in glioma cell migration. Among the ASIC subunits, only ASIC1a has been found be calcium permeable. However, it has not been determined whether Ca2+/calmodulin-dependent protein kinase II (CaMKII) regulates ASIC1 in glioblastoma multiforme (GBM). Herein, we report that ASIC1 and CaMKII assemble to form a functional complex at the plasma membrane of GBM cells. We found that migration ability was significantly attenuated in GBM cells that were pre-treated with autocamtide-2-related inhibitory peptide (AIP), a CaMKII-specific inhibitor, or psalmotoxin 1 (PcTX-1), a selective ASIC1 blocker. Furthermore, the inhibitory effect of AIP or PcTX-1 on migration was diminished when ASIC1 was knocked down in GBM cells; when ASIC1 knockdown GBM cells were concurrently treated with these two inhibitors, cell migration was slightly but significantly decreased. Using whole-cell patch-clamp recordings, we detected an amiloride-sensitive current in GBM cells, and this current was significantly inhibited by both PcTX-1 and AIP. Moreover, the magnitude of this current was dramatically decreased when ASIC1 was knocked down in GBM cells. The addition of AIP failed to further decrease the amplitude of this current. Taken together, these data suggest that ASIC1 and CaMKII form a functional complex in GBM cells. Furthermore, it can be concluded that CaMKII regulates the activity of ASIC1, which is associated with the ability of GBM cells to migrate.

MiR-139 inhibits Mcl-1 expression and potentiates TMZ-induced apoptosis in glioma.

AIMS: Mcl-1, an antiapoptotic member of the Bcl-2 family, is overexpressed in human glioblastoma, conferring a survival advantage to tumor cells. The mechanisms underlying its dysregulation have not been clarified. In this study, we explored the involvement of micro-RNAs that acted as endogenous sequence-specific suppressors of gene expression. METHODS AND RESULTS: Using computational and TCGA analysis, we identified miR-139 as being downregulated in glioblastoma in comparison with human brain tissue, as well as possessing a putative target site in Mcl-1 mRNA. Overexpression of miR-139 led to a clear decrease in Mcl-1 expression in gliomas. Reporter assays revealed direct post-transcriptional regulation involving miR-139 and the 3'-untranslated region of Mcl-1. Human glioma tissues with low expression of miR-139 displayed higher expression of Mcl-1 protein than those with high expression, suggesting that low miR-139 contributes to Mcl-1 overexpression. In addition, upregulation of miR-139 suppressed the proliferation and enhanced temozolomide (TMZ)-induced apoptosis. Finally, we observed that Mcl-1 knockdown resulted in similar effects compared with miR-139 transfection. CONCLUSION: Our results suggested that miR-139 negatively regulated Mcl-1 and induced apoptosis in cooperation with an anticancer drug TMZ in glioma.

Screening and identification of permeable components in a combined prescription of Danggui Buxue decoction using a liposome equilibrium dialysis system followed by HPLC and LC-MS.

A new method, i.e., liposome equilibrium dialysis followed by HPLC and LC-MS analysis, has been developed for the screening of permeable components in combined prescriptions of Danggui Buxue decoction (CPDBD). Multiple permeable components were simultaneously predicted by comparison of chromatograms of CPDBD extract before and after interaction with liposome membranes. A diode-array detector (DAD) and an evaporative light scattering detector (ELSD) were used, and the permeable compounds were identified by comparison with the available reference compounds and confirmed by on-line LC-MS. About fifteen compounds in a CPDBD extract were found to interact with liposome membranes. They were identified as calycosin-7-O-beta-D-glucoside (1), senkyunolide I or H (2), ononin (3), (6alphaR,11alphaR)-9,10-dimethoxypterocarpan-3-O-beta-D-glucoside (4), (3R)-2'-hydroxy-3',4'-dimethoxyisoflavan-7-O-beta-D-glucoside (5), calycosin (6), astragaloside IV (7), isoastragaloside II (8), formononetin (9), (6alphaR, 11alphaR),-3-hydroxy-9,10-dimethoxypterocarpan (10), (3R)-7,2'-dihydroxy-3',4'-dimethoxyisoflavan (11), astragaloside I (12), isoastragaloside I (13), E-ligustilide (14), and Z-ligustilide (15), respectively. Among all permeable components, 1, 3, 6, and 9 (flavonoids), 2, 14, and 15 (phthalides), and 7 (saponins) have been considered as major bioactive components in CPDBD. Therefore, this new method appears useful as a first step in the screening of bioactive components in natural products including Traditional Chinese Medicines (TCMs).

Live cell extraction and HPLC-MS analysis for predicting bioactive components of traditional Chinese medicines.

A novel strategy for predicting bioactive components in traditional Chinese medicines (TCM) using live cell extraction and high performance liquid chromatography-diode array detection-mass spectrometry (HPLC-DAD-MS) analysis was proposed. The hypothesis is that when cells are incubated together with the extract of TCM, the potential bioactive components in the TCM should selectively combine with the cells, and the relative concentrations of the cell-combining components in the suspension medium should decrease, while the cell-combining components would be detectable in the extract of denatured cells. The identities of the cell-combining components could be determined by HPLC-DAD-MS analysis. Using the proposed approach, the potential bioactive components of Danggui Buxue decoction, a commonly used TCM for anaemia, and its compositions, Radix Angelica Sinensis and Radix Astragli for endothelial cells, were investigated. Six compounds in the extract of Danggui Buxue decoction were detected as the components selectively combined with endothelial cells, among them two were contributed by Radix Angelica Sinensis, and four by Radix Astragli. The identities of four of the six potential bioactive compounds were elucidated as ononoside, calycosin, 3-butylphthalide and ligustilide by HPLC-DAD-MS analysis. The results indicate that the proposed approach may be applied to predict the bioactive candidates in TCM.

Study of pi halogen bonds in complexes C2H(4-n)Fn-ClF (n = 0-2).

The pi-halogen bond may be considered, in a broad sense, essentially a pi-hydrogen bond. Using the counterpoise-corrected potential energy surface method (interaction energy optimization), the stationary structures of the C2H(4-n)Fn-ClF (n = 0-2) complexes with all real frequencies have been obtained at the MP2/aug-cc-pVDZ level. For C2H(4-n)Fn-ClF (n = 0-2), the pi-halogen bond has a long distance and is elongated by the F substituent effect. The pi-halogen bond length order is 2.661 A for C2H4-ClF < 2.745 A for C2H3F-ClF < 2.766 A for g-C2H2F2-ClF < 2.8076 A for trans-C2H2F2-ClF < 2.8079 A for cis-C2H2F2-ClF. For three complexes C2H3F-ClF, g-C2H2F2-ClF, and cis-C2H2F2-ClF, the pi-halogen bonds are further shifted and sloped by the F substituent effect. The F substituent effect reduces also the interaction energy of the pi-halogen bond. The interaction energies are respectively -3.7 for C2H4-ClF, -2.8 for C2H3F-ClF, -2.3 for g-C2H2F2-ClF, -1.9 for cis-C2H2F2-ClF, and -1.8 kcal/mol for trans-C2H2F2-ClF, at the CCSD(T)/aug-cc-pVDZ level. The electron correlation contribution of the interaction energy is large for C2H(4-n)Fn-ClF (n = 0-2), which shows that the stabilities of the pi-halogen bond systems results primarily from the dispersion interaction. In the double F substituent systems, the interaction energy of the pi-halogen bond structure with a longer interaction distance is larger than that of the corresponding pi-hydrogen bond structure with a shorter interaction distance. This may be because there are the large electron correlation contributions of the interaction energy, and a secondary interaction between lone pairs of Cl atom and some atoms (H, C) with positive charges in the pi-halogen bond structure.

Inverse sodium hydride: density functional theory study of the large nonlinear optical properties.

"Inverse sodium hydride" (AdzH(+)Na-) is an alkalide compound synthesized in recent experiments containing the unusual charge distribution H+ and Na- (inverse charge state). The new class of compounds interests scientists to investigate their especial structures and properties. In this paper, the structures of three alkalides compounds, (Me)3NH(+)Na-, AdzH(+)Na-, and AdzLi(+)Na-, have been obtained in theory. Especially, the structure of AdzLi(+)Na- is still researched by experimental scientists. We investigated the NLO properties of the alkalides complexes for the first time and found that inverse sodium hydride AdzH(+)Na- has a considerably large NLO response beta0 = 5.7675 x 10(4) au by density functional theory (DFT). To understand the essential features of the large NLO properties, four related systems have been also calculated. Their first hyperpolarizabilities are beta0 = 7.357 x 10(3) au for (Me)3NH(+)Na-, beta0 = 3.9 au for (Me)3NH+, beta0 = 1.10 x 10(2) au for (Me)3NH(+)Cl-, and beta0 = 6.20681 x 10(5) au for AdzLi(+)Na-, respectively. By comparing, we found that, first, the Na- anion plays a crucial role in the considerably large first hyperpolarizability of inverse sodium hydride and, second, the first hyperpolarizability of inverse sodium hydride increases with the charge value of the sodium anion. The above results are useful for designing potential NLO materials.

Theoretical investigation of the large nonlinear optical properties of (HCN)n clusters with Li atom.

Two new classes of (HCN)(n)...Li and Li...(HCN)(n) (n = 1, 2, 3) clusters with the electride characteristic are formed in theory by the metal Li atom attaching to the (HCN)(n) (n = 1, 2, 3) clusters. Because of the interaction between the Li atom and the (HCN)(n) part, the 2s valence electron of the Li atom becomes a loosely bound excess electron. Our high-level ab initio calculations show that these new clusters with the excess electron have large first hyperpolarizabilities, for example, beta(0) = -15,258 au for (HCN)...Li and beta(0) = -3401 au for Li...(HCN) at the QCISD/6-311++G(3df,3pd) level (only beta(0) = -2.8 au for HCN monomer(26)). Obviously, the excess electron from the Li atom plays a crucial role in the large first hyperpolarizabilities of these clusters. The beta(0) value of (HCN)(n)...Li (beta(0) > 10(4) au, from sigma --> pi* transition) is larger than that of Li...(HCN)(n) (beta(0) > 10(3) au, from sigma --> sigma* transition) for n = 1, 2, or 3. In addition, two interesting rules have been observed. They are that |beta(0)| decreases with lengthening of the HCN chain for (HCN)(n)...Li clusters and that |beta(0)| increases as n increases for Li...(HCN)(n) clusters. In this paper, we discuss two classes of clusters that are highly similar to the electride structure model, of which the structural characteristics are that alkali metal atoms ionize to form cations and trapped electrons under the action of other polar molecules. Thus, the investigation on the large first hyperpolarizabilities of (HCN)(n)...Li and Li...(HCN)(n) (n = 1, 2, 3) may prompt one to study the unusual nonlinear optical responses of some electrides.

Characteristic of structures and pi-hydrogen bond of dimers C2H4-nFn-HF (n=0,1,2).

By the counterpoise-correlated potential energy surface method (interaction energy optimization), five structures of the C(2)H(4-n)F(n)-HF (n = 0,1,2) dimers with all real frequencies have been obtained at MP2/aug-cc-pVDZ level. The influence of F substituent effect on the structure and pi-hydrogen bond of dimer has been discussed. For C(2)H(4-n)F(n)-HF (n = 1,2), the pi-hydrogen bonds are elongated comparing with that for C(2)H(4)-HF. For C(2)H(3)F-HF, g-C(2)H(2)F(2)-HF, cis-C(2)H(2)F(2)-HF, the pi-hydrogen bonds are further deformed. These changes (elongate, shift, and deformation) of pi-hydrogen bond mainly come from deformation of pi-electron cloud of C=C bond. The pi-electron cloud is pushed towards the one C atom, the pi H-bond shift also to the C direction. Since the two lobes of pi-electron cloud have deviated slightly from the molecular vertical plane passing through C=C bond, the pi-hydrogen bond is sloped. Intermolecular interaction energies of the dimers are calculated to be -3.9 for C(2)H(4)-HF, -2.8 for C(2)H(3)F-HF, -2.1 for g-C(2)H(2)F(2)-HF, -1.6 for cis-C(2)H(2)F(2)-HF, -1.3 kcal/mol for trans-C(2)H(2)F(2)-HF, at CCSD(T)/aug-cc-pVDZ level.