Association between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and the risk of post-stroke depression: A cross-sectional study.

BACKGROUND: Limited observational research has explored the relationship between the non-high-density lipoprotein cholesterol (non-HDL-C) to high-density lipoprotein cholesterol (HDL-C) ratio (NHHR) and the risk of post-stroke depression (PSD). This study aims to investigate the potential associations between NHHR and PSD. METHODS: A cross-sectional study was conducted using data from stroke participants aged 20 and older, sourced from the National Health and Nutrition Examination Survey (NHANES) spanning 2005 to 2018. Depression was assessed using the PHQ-9 questionnaire. The association between NHHR and PSD risk was evaluated through weighted multivariate logistic regression and restricted cubic spline (RCS) models. Subgroup and sensitivity analyses were performed to validate the findings. RESULTS: In the continuous model, the NHHR value for the PSD group (3.23±1.84) was significantly higher than that of the non-PSD group (2.79±1.40, p=0.015). Logistic regression analysis in the fully adjusted model revealed a positive association between NHHR and PSD (OR 1.16, 95 % CI 1.03-1.30, p=0.016). Interaction tests showed no significant differences across strata (p > 0.05 for interaction). Restricted cubic spline results indicated a linear dose-response relationship between NHHR and PSD risk (P for non-linearity = 0.6). This association persisted in various subgroup analyses. CONCLUSION: NHHR was significantly correlated with an increased risk of PSD among U.S. adults. Further re-search on NHHR could contribute to the prevention and treatment of PSD.

Genetically proxied appendicular lean mass and stroke risk: A two-step mendelian randomization study.

BACKGROUND AND PURPOSE: Prior observational studies have suggested a strong correlation between sarcopenia and stroke, but the causal link between them remains uncertain. This study aims to investigate the associations between genetically predicted sarcopenia-related traits and stroke using a two-step Mendelian randomization (MR) approach. METHODS: Genome-wide association study (GWAS) summary data for sarcopenia-related traits were acquired from the UK Biobank. Genetic associations for ischemic stroke (IS) and its subtypes were selected from the MEGASTROKE consortium comprising European ancestry participants. GWAS summary data for cerebral hemorrhage were obtained from the FinnGen consortium, including intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH). MR estimates were calculated using the inverse-variance weighted (IVW) method. The robustness of results was assessed for heterogeneity and pleiotropy of individual single nucleotide polymorphisms (SNPs). RESULTS: Higher appendicular lean mass (ALM) exhibited a potential causal association with a reduced incidence of large artery atherosclerosis (LAA) (odds ratio [OR] = 0.81, 95% confidence interval [CI]:0.71-0.93; P = 0.003) and small vessel disease (SVD) (OR = 0.83, 95% CI:0.74-0.94; P = 0.002). The associations of ALM with IS and ICH were compromised after adjusting for body fat and physical activity with multivariable MR. Two-step MR mediation analysis explored 33 candidate mediators, among which hypertension and SBP accounted for more than 10% of the mediation proportion in the relationship between ALM and stroke and its subtypes. CONCLUSION: Our research findings indicate that lower ALM is associated with a increased risk of stroke . It is necessary to explore the specific protective mechanisms of higher ALM for preventing stroke occurrence.

Prevalence of small vessel disease and incidental DWI-positive lesions in patients with aneurysmal subarachnoid hemorrhage versus intracerebral hemorrhage.

INTRODUCTION: Aneurysmal subarachnoid hemorrhage (aSAH) and intracerebral hemorrhage (ICH) are main forms of hemorrhagic stroke. Data regarding cerebral small vessel disease (SVD) burden and incidental small lesions on diffusion-weighted imaging (DWI) following aSAH are sparse. PATIENTS AND METHODS: We retrospectively analyzed a prospective cohort of aSAH and ICH patients with brain MRI within 30 days after onset from March 2015 to January 2023. White matter hyperintensity (WMH), lacune, perivascular space, cerebral microbleed (CMB), total SVD score, and incidental DWI lesions were assessed and compared between aSAH and ICH. Clinical and radiological characteristics associated with small DWI lesions in aSAH were investigated. RESULTS: We included 180 patients with aSAH (median age [IQR] 53 [47-61] years) and 299 with ICH (63 [53-73] years). DWI lesions were more common in aSAH than ICH (47.8% vs 14.4%, p < 0.001). Higher total SVD score was associated with ICH versus aSAH irrespective of hematoma location, whereas DWI lesions and strictly lobar CMBs were correlated with aSAH. Multivariable analysis showed that shorter time from onset to MRI, anterior circulation aneurysm rupture, CMB ⩾ 5, and total SVD score were associated with DWI lesions in aSAH. DISCUSSION AND CONCLUSION: Incidental DWI lesions and strictly lobar CMBs were more frequent in aSAH versus ICH whereas ICH had higher SVD burden. Incidental DWI lesions in aSAH were associated with multiple clinical and imaging factors. Longitudinal studies to investigate the dynamic change and prognostic value of the covert hemorrhagic and ischemic lesions in aSAH seem justified.

Age-related differences in risk factors, clinical characteristics, and outcomes for intracerebral hemorrhage.

Background and purpose: Intracerebral hemorrhage (ICH) is a severe form of stroke that remains understudied in the young adults. We aimed to investigate the clinical presentation, and risk factors associated with ICH in this age group and compare them to older patients. Methods: Our study included ICH patients admitted between March 2016 and December 2021 in the First Affiliated Hospital of Chongqing Medical University from our ongoing prospective cohort database. Demographic characteristics, etiology, risk factors, and clinical outcomes were compared between elderly and young patients. Furthermore, logistic regression analysis was employed to explore risk factors associated with the functional outcome at 3-months. Results: We selected 1,003 patients (mean age, 59.9 ±13.8 years old), 746 (74.4%) patients were aged >50 years. The logistic regression analysis showed young patients have a higher proportion of secondary ICH, higher white blood cell count and higher body mass index (BMI), but less diabetes mellitus. Of all patients, predictors of 3-month functional independence was first-ever ICH and age ≤50 years. The history of nephropathy and stroke, higher baseline NIHSS score, larger hematoma volume, and the presence of hydrocephalus were associated with poor outcomes. And the white blood cell count could significantly influence the prognosis among young ICH patients. Three-month functional outcome based on modified Rankin scale score was better in young patients than the elderly (OR, 1.232; 95% CI, 1.095-1.388; p < 0.001). Conclusions: The highest incidence of ICH occurs in the age groups of 50-59 and 60-69. ICH in young adults had higher white blood cell and BMI compared to the elderly, and differs in etiological distribution. The young patients also had similar short-term mortality but more favorable functional outcomes than the elderly. Furthermore, NIHSS score and larger hematoma volumes were associated with poor outcome in all patients.

Microgravity induces inhibition of osteoblastic differentiation and mineralization through abrogating primary cilia.

It is well documented that microgravity in space environment leads to bone loss in astronauts. These physiological changes have also been validated by human and animal studies and modeled in cell-based analogs. However, the underlying mechanisms are elusive. In the current study, we identified a novel phenomenon that primary cilia (key sensors and functioning organelles) of rat calvarial osteoblasts (ROBs) gradually shrank and disappeared almost completely after exposure to simulated microgravity generated by a random positioning machine (RPM). Along with the abrogation of primary cilia, the differentiation, maturation and mineralization of ROBs were inhibited. We also found that the disappearance of primary cilia was prevented by treating ROBs with cytochalasin D, but not with LiCl or dynein light chain Tctex-type 1 (Dynlt1) siRNA. The repression of the differentiation, maturation and mineralization of ROBs was effectively offset by cytochalasin D treatment in microgravity conditions. Blocking ciliogenesis using intraflagellar transport protein 88 (IFT88) siRNA knockdown inhibited the ability of cytochalasin D to counteract this reduction of osteogenesis. These results indicate that the abrogation of primary cilia may be responsible for the microgravity's inhibition on osteogenesis. Reconstruction of primary cilia may become a potential strategy against bone loss induced by microgravity.

[Low-frequency pulsed electromagnetic fields promotes rat osteoblast differentiation in vitro through cAMP/PKA signal pathway].

OBJECTIVE: To study whether low-frequency pulsed electromagnetic fields promotes the differentiation of cultured rat osteoblasts through the cAMP/PKA signal pathway. METHODS: Rat calvarial osteoblasts isolated by enzyme digestion were exposed to 50 Hz 0.6 mT low-frequency pulsed electromagnetic field for varying lengths of time, and the concentration of cAMP and levels of phosphorylated PKA in the cells were assayed. In cells treated with DDA to inhibit the activity of adenylate cyclase, the changes of ALP activity and transcription of osteogenic gene were detected after exposure to low-frequency pulsed electromagnetic field. The changes of osteogenic gene transcription and protein expression were tested in the osteoblasts pretreated with KT5720 in response to low-frequency pulsed electromagnetic field exposure. RESULTS: The intracellular cAMP concentration in the cells increased significantly at 20 min during exposure to low-frequency pulsed electromagnetic field, began to decrease at 40 min during the exposure, and increased again after a 2-h exposure; the same pattern of variation was also observed in p-PKA level. Application of DDA and KT5720 pretreatment both suppressed the increase in ALP activity and osteogenic gene transcription induced by electromagnetic field exposure. CONCLUSION: Low- frequency pulsed electromagnetic field exposure improves the differentiation of cultured rat osteoblasts by activating cAMP/PKA signal pathway.

Pulsed electromagnetic fields stimulate osteogenic differentiation and maturation of osteoblasts by upregulating the expression of BMPRII localized at the base of primary cilium.

Pulsed electromagnetic fields (PEMFs) have been considered as a potential candidate for the prevention and treatment of osteoporosis, however, the mechanism of its action is still elusive. We have previously reported that 50Hz 0.6mT PEMFs stimulate osteoblastic differentiation and mineralization in a primary cilium- dependent manner, but did not know the reason. In the current study, we found that the PEMFs promoted osteogenic differentiation and maturation of rat calvarial osteoblasts (ROBs) by activating bone morphogenetic protein BMP-Smad1/5/8 signaling on the condition that primary cilia were normal. Further studies revealed that BMPRII, the primary binding receptor of BMP ligand, was readily and strongly upregulated by PEMF treatment and localized at the bases of primary cilia. Abrogation of primary cilia with small interfering RNA sequence targeting IFT88 abolished the PEMF-induced upregulation of BMPRII and its ciliary localization. Knockdown of BMPRII expression level with RNA interference had no effects on primary cilia but significantly decreased the promoting effect of PEMFs on osteoblastic differentiation and maturation. These results indicated that PEMFs stimulate osteogenic differentiation and maturation of osteoblast by primary cilium-mediated upregulation of BMPRII expression and subsequently activation of BMP-Smad1/5/8 signaling, and that BMPRII is the key component linking primary cilium and BMP-Smad1/5/8 pathway. This study has thus revealed the molecular mechanism for the osteogenic effect of PEMFs.

[3D Collagen Hydrogel Culture of Rat Calvarial Osteoblasts].

OBJECTIVE: To establish a collagen hydrogel three-dimensional culture model with rat calvarial osteoblasts (ROBs). METHODS: ROBs were obtained through enzyme digestion of segregated neonatal SD rat skull. The collagen hydrogel three-dimensional culture model was established by mixing ROBs with different concentrations of type I rat tail collagen (collagen concentration of 1, 2, 3 mg/mL), DMEM medium and NaOH under adjusted PH and a temperature of 37 degrees C. Cell viability and activity were detected by FDA/PI staining and CCK-8 3 d after cell culture. The optimal culture method of 3D collagen hydrogel was identified. Cell distribution was observed using scanning electron microscopy and HE staining. RESULTS: ROBs collagen was formed firmly at 2 mg/mL, which had significantly higher levels of cell viability and activity than those at 1 mg/mL and 3 mg/mL. Scanning electron microscopy and HE staining showed that cells under the 2 mg/mL collagen culture system adhered with collagen tightly and distributed homogeneously. CONCLUSION: A collagen hydrogel 3D culture model was established successfully by mixing ROBs with collagen at 2 mg/mL.

[ROLES OF SIGNAL MOLECULE p38 INVOLVED IN MINERALIZATION AND MATURATION OF OSTEOBLASTS PROMOTED BY LOW FREQUENCY PULSED ELECTROMAGNETIC FIELDS].

OBJECTIVE: To investigate whether signal molecule mitogen-activated protein kinases (MAPKs) involves in the process of the mineralization and maturation of rat calvarial osteoblasts promoted by 50 Hz, 0.6 mT pulsed electromagnetic fields. METHODS: Rat calvarial osteoblasts were obtained by enzyme digestion from the skull of 6 neonatal Wistar rats of SPF level. The primary osteoblasts were treated in 50 Hz and 0.6 mT pulsed electromagnetic fields for 0, 5, 10, 20, 40, 60, and 120 minutes; the protein expression of phosphorylated MAPKs was detected by Western blot. The osteoblasts were randomly divided into group A (control group), group B (low frequency pulse electromagnetic fields treatment group), group C (SB202190 group), and group D (SB202190+low frequency pulse electromagnetic fields treatment group); the alkaline phosphatase (ALP) activities were tested after corresponding treatment for 1, 4, and 7 days. The corresponding treated more than 90% confluenced osteoblasts were cultured under condition of osteogenic induction, then ALP staining and alizarin red staining were carried out at 9 and 12 days respectively. RESULTS: The results of Western blot showed that there was no significant changes in the protein expressions of phosphorylated level of extracellular signal-related kinases 1/2 and c-Jun amino N-terminal kinases 1/2 in 50 Hz, 0.6 mT pulsed electromagnetic fields P>0.05), but the phosphorylated level of p38 began to increase at 5 minutes, peaked at 40 minutes, then gradually decreased, and it was significantly higher at 5-120 minutes than at 0 minute (P<0.05). After the activities of p-p38 was inhibited by inhibitor SB202190, the ALP activities, positive colonies and area of ALP and calcified nodules of group B were significantly higher than groups A, C, and D (P<0.05). CONCLUSIONS: p38 is one of the signal molecules involved in the process of the mineralization and maturation of rat calvarial osteoblasts promoted by 50 Hz, 0.6 mT pulsed electromagnetic fields.

[Screening the Optimal Time of Sinusoidal Alternating Electromagnetic Field for the Bone Biomechanical Properties of Rat].

The present research is to investigate the time effect of sinusoidal electromagnetic fields(SEMFs)at different exposure time on the biomechanical properties in rats,and to find a best time for improving biomechanical properties.Forty female SD rats were randomly divided into five groups,i.e.control group,45 min SEMFs group,90 min SEMFs group,180 min SEMFs group,and 270 min SEMFs group.In addition to the control group,other groups were exposed to 50 Hz and 0.1mT magnetic field every day for the corresponding time periods.After eight weeks,bone mineral density(BMD),bone biomechanics,bone tissue morphology,micro-CT and pathological examination were performed.The results showed that there was no abnormal pathological finding in the experimental groups.In the 90 min SEMFs group,BMD,femur maximum load,elastic modulus,yield strength,trabecular number(Tb.N),trabecular thickness(Tb.Th)and trabecular area(Tb.Ar)percentage were all significantly higher than those in the control group(P<0.01),and trabecular separation(Tb.Sp)was significantly lower than that of the control group(P<0.01).However,for other experimental groups,some indices showed statistical significance compared to the control group(P<0.05),but some did not(P>0.05).This study showed that under 50 Hz and 0.1 mT SEMFs,90 min is the best time that can effectively increase bone mineral density,improve the bone tissue microstructure organization and the biomechanical properties.

[Icariin enhances differentiation and maturation of rat calvarial osteoblasts in collagen hydrogel three-dimensional culture].

OBJECTIVE: To investigate the effects of icariin on the differentiation and maturation of rat calvarial osteoblasts(ROB) in collagen hydrogel three-dimensional culture. METHODS: ROB were obtained by enzyme digestion from the segregated neonatal SD rats skull and were embedded in 2 mg/mL rat tail collagen for three-dimensional culture. The growth state of ROB was observed by FDA/PI staining, HE staining and scanning electron microscopy. ROB were treated with icariin at the concentration of 1 × 10⁻4, 1 × 10⁻5, 1 × 10⁻6 and 1 × 10⁻7 mol/L respectively. The activity of alkaline phosphatase(ALP) was detected after 3, 6, 9 d of icariin treatment. Three-dimensional cultured ROB were treated with optimal concentration icariin for 12, 24, 36, 48 h and total RNA was extracted and the mRNA expressions of bone morphogenetic protein-2 (BMP-2), Runt-related transcription factor 2 (RUNX-2) and Osterix were detected by real time RT-PCR. The protein expression of BMP-2, RUNX-2 and Osterix were examined by Western-blotting. RESULTS: ROB were cultured in collagen hydrogel successfully. FDA/PI staining, HE staining, and scanning electron microscopy showed that ROB adhered with collagen tightly and distributed homogeneously. Icariin at final concentration of 1 × 10⁻5, 1 × 10⁻6 and 1×10⁻7 mol/L all enhanced the activity of ALP of collagen hydrogel three-dimensional cultured ROB, and 1 × 10⁻6 mol/L was the optimal concentration. Besides, icariin (1 × 10⁻6 mol/L) increased mRNA and protein expression of BMP-2、RUNX-2 and Osterix compared to control group. CONCLUSION: Icariin can enhance the expression of osteogenic markers of ROB in collagen hydrogel three-dimensional culture significantly.

[Establishment of osteoblast primary cilia model removed by chloral hyrate].

OBJECTIVE: To establish osteoblast model, primary cilla model was removed by chloral hyrate, observe effects of osteoblast primary cilla moved on enhancing ALP staining and calcified nodules staining in electromagnetic field. METHODS: Three 3-day-old male SD rats weighed between 6 and 9 g were killed, cranial osteoblast was drawed and adherencing cultured respectively. Cells were subcultured and randomly divided into 4 groups until reach to fusion states. The four groups included chloral hydrate non-involved group (control group), 2 mM, 4 mM and 8 mM chloral hydrate group, and cultured in 37 °C, 5% CO2 incubator for 72 h. Morphology of primary cilla was observed by laser confocal scanning microscope, and incidence of osteoblast primary cilia was analyzed by Image-Pro Plus 6.0 software. Cells in the correct concentration group which can removed cillia most effectively were selected and divided into 3 groups, including control group (C), Electromagnetic fields group (EMFs), and EMFs with 4 mM chloral hydrate group. DMEM nutrient solution contained 10%FBS were added into three groups and cultured for 9 days and formation of ALP were observed by histochemical staining of alkaline phosphatase. After 12 days' cultivation, formation of mineralization nodes was observed by alizarin red staining. RESULTS: Compared with control group and 2mM chloral hydrate group,4 mM chloral hydrate group could effectively remove osteoblast primary cilla (P<0.01). Removal of osteoblast primary cilla could weaken the formation of ALP and mineralization nodes in osteoblast in EMFS. Compared with EMFs group, the area of ALP and mineralization nodes in EMFs with 4 mM chloral hydrate group were decreased obviously (P<0.01). CONCLUSION: 4mM chloral hydrate could effectively remove osteoblast primary cilia. Primary cilla participate in EMFs promoting formation of ALP and mineralization nodes in osteoblast and provide new ideas for exploring mechanism of EMFs promoting osteoblast maturation and mineralization.

[Icariin promote maturation of osteoblasts in vitro by an estrogen-independent mechanism].

OBJECTIVE: To investigate the estrogenic activity of icariin and genistein with estrogen-dependent human breast cancer (MCF-7) cells. METHOD: MCF-7 cells were incubated with media containing 5% charcoal dextran-treated FBS in phenol red-free media for 48 h. CCK-8 kit was used to study the impact of defferent concentration of icariin and genistein on MCF-7 proliferation in vitro. Optimal concentration icariin and genistein were added into medium and total RNA was isolated after 12, 24, 36, 48 h. The gene expression of ERalpha, ERbeta, PS2, and PR were investigated by Real-time RT-PCR Total protein was also isolated and secretion of ERalpha, ERbeta, PS2, and PR were examined by Western blot. RESULT: 10 micromol x L(-1) icariin and genistein could promote the proliferation of MCF-7 evidently. However, the ability of genistein to promote the proliferation was better than icariin. With the concentration of 10 micromol x L(-1), genistein group had a stronger expression of ERa, PS2 and PR mRNA levels than icariin while ERbetaexpression had no significant difference in two group. The same effects were detected by western blotting. CONCLUSION: Both genistein and icariin have a strong estrogen-like effect, but the estrogenic activity of genistein is stronger than icariin. It showed that the activity of icariin is stron-ger than genistein to promote ROB maturation. So it must be that icariin promotes the maturation of osteoblasts in vitro by a estogen-independent mechanism.

Discordances in ER, PR and HER2 receptors between primary and recurrent/metastatic lesions and their impact on survival in breast cancer patients.

The aim of this study was to evaluate the frequency and prognostic impact of changes in the estrogen (ER), progesterone (PR) and human epidermal growth factor receptor 2 (HER2) status between primary and recurrent/metastatic lesions (RML). We investigated 133 breast cancer patients for ER, PR and HER2 status of primary and RML and their follow-up records. Among 133 patients with RML, discordance rate for ER, PR, and HER2 was 18.8, 33.8, and 6.8%, respectively. ER, PR and HER2 discordance were observed in 20.0, 38.1 and 6.7% of the patients with distant metastasis, and in 14.3, 17.9 and 7.1% of the patients with locoregional recurrence. The mean time between the primary diagnosis and last contact or death was 57 (range 22-78) months and between the recurrence biopsy and last contact or death was 17 (range 1-33) months. Among 133 patients with RML, the ER-discordant cases and ER-loss cases experienced a worse overall survival (OS) (p=0.001 and p=0.016, respectively) and post-recurrence survival (PRS) (p=0.001 and p=0.018, respectively), compared with the respective concordant cases. The HER2-discordant patients and HER2-loss patients had a poorer OS (p=0.008 and p=0.001, respectively) and PRS (p=0.004 and p=0.000, respectively) than the respective concordant cases. Among 105 patients with distant metastasis, ER discordance, ER loss, HER2 discordance and HER2 loss, compared with the respective concordant cases, resulted in a worse OS and PRS (p<0.05 for all). Our findings show an evident change in ER, PR and HER2 between breast primary tumors and relapsing tumors. The unstable status for ER or HER2 in breast cancer seems to be clinically significant and to correlate with a worse prognosis.

Prognostic role of nucleophosmin in colorectal carcinomas.

AIM: Recent research suggests that nucleophosmin (NPM) may be a prognostic marker in colorectal carcinomas (CRC). We here tested its use to predict the survival of CRC patients. METHODS: We investigated NPM expression by immunohistochemistry in histologically normal to malignant colorectal tissues and evaluated its association with clinicopathological variables. Overall and disease-free survival after tumor removal were calculated by the Kaplan-Meier method, and differences in survival curves were analyzed by the log-rank test. The Cox proportional hazards model was used for multivariate analysis of prognostic factors. RESULTS: NPM expression was found significantly upregulated in CRC compared to adjacent colorectal tissue, villous adenoma, tubular adenoma and normal colorectal mucosa (p<0.05 for all). NPM expression was statistically linked to cancer embolus, lymph node metastasis, differentiation grade, and recurrence of CRC. Overall and disease-free survival of NPM-negative CRC patients tended to be better than those for patients with NPM-positive lesions (log-rank statistic, p<0.05 for all). Multivariate analysis indicated NPM expression as an independent prognostic indicator for CRC patients (p<0.05 ). CONCLUSION: Our results suggest that NPM expression can predict the survival of CRC patients. Prognosis of CRC is determined by not only many known prognostic factors but also by NPM expression.

Changes in ER, PR and HER2 receptors status after neoadjuvant chemotherapy in breast cancer.

Previous studies have reported conflicting results regarding the impact of neoadjuvant chemotherapy (NAC) on estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status in breast cancer. Our aim was to investigate whether NAC induces some selective change in the breast biomarkers. We retrospectively detected the immunohistochemical results of ER, PR and HER2 between the core biopsy and surgical excision specimens in 113 patients with NAC. As a control group, we analyzed sample pairs from 102 patients without NAC. Fourteen (12.4%) of 113 patients undergoing NAC showed the ER status modulation in the surgically removed specimen as compared with only 4 (3.9%) of 102 women without NAC (p=0.025). Eighteen (15.9%) of 113 patients given NAC appeared in the PR status alteration in the final surgical specimen, whereas only 7 (6.9%) of 102 patients without NAC did (p=0.038). The HER2 status shift was found in 17 (15.0%) of 113 patients with NAC and in 6 (5.9%) of 102 patients without NAC, respectively (p=0.030). Neoadjuvant chemotherapy does change ER, PR and HER2 status in a statistically significant manner. Retesting these biomarkers of the residual tumor should be considered to improve future tailored adjuvant therapies.

[Mechanisms of icariin in regulating bone formation of osteoblasts and bone resorption of osteoclasts].

OBJECTIVE: To investigate the molecular mechanisms of icariin (ICA) in regulating the bone formation of osteoblasts and the bone resorption of osteoclasts. METHODS: Primary osteoblast cell cultures were obtained from newborn rat calvarial. Calcified nodules were stained by alizarin red. The mRNA levels of osterix (OSX), runt-related transcription factor 2 (Runx-2), alkaline phosphatase (ALP), Collagen1, osteoprotegerin (OPG), and receptor activator of nuclear factor-ΚB ligand (RANKL) were analyzed by quantitative real-time RT-PCR, the protein levels of OPG, RANKL, and Collagen1 were examined by Western blotting, and the intracellular Ca(2+) concentration of osteoblasts was measured on a flow cytometer using the Cellquest program. RESULTS: Compared with control group, ICA markedly promoted bone formation by significant up-regulating the gene expressions of OSX, Runx-2,ALP, and Collagen1, the protein expression of Collagen1(all P<0.01), and the Ca(2+) concentration. Furthermore, ICA remarkably inhibited bone resorption by significant up-regulating the mRNA and protein expressions of OPG as well as the OPG/RANKL ratio. CONCLUSIONS: ICA could promote bone formation of osteoblasts through inducting the gene expressions of OSX,Runx-2, ALP and Collagen1, and the protein expressions of Collagen1, and by increasing the Ca (2+) concentration. Moreover, ICA could inhibit bone resorption of osteoclasts through regulating OPG/RANKL signal pathway.

A hierarchical Co-Fe LDH rope-like nanostructure: facile preparation from hexagonal lyotropic liquid crystals and intrinsic oxidase-like catalytic activity.

Hierarchical rope-like structures based on Co-Fe layered double hydroxide (LDH) nanosheets were synthesized by the coprecipitation method from a hexagonal lyotropic liquid crystal (LLC) nanoreactor, and were characterized by X-ray powder diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FT-IR), thermogravimetric (TG) and inductively coupled plasma (ICP) analyses. It was found that the rope-like LDH structures were composed of LDH nanosheets with a lateral size of about 200-400 nm and an average thickness of 4.47 nm in the form of face-to-edge interactions. The length and the diameter of the rope-like assemblies were about 3-6 µm and 150-300 nm, respectively, and their aspect ratio was as high as 20. Interestingly, the LDH rope-like assemblies were ordered to form an array with the oriented directions parallel to each other. A formation mechanism for the hierarchical LDH structures in the LLC media was proposed. In addition, the catalytic activity of the hierarchical rope-like LDH assemblies for the oxidation reaction of the typical horseradish peroxidase (HRP) substrate, 3,3',5,5'-tetramethylbenzidine (TMB), was examined, and results revealed that they had a higher oxidase-like catalytic activity towards the oxidization of TMB by dissolved oxygen. We expect that the hierarchical rope-like LDHs can offer the potential applications in aqueous redox catalysts, biosensors, medical diagnostics and so on.

Study on nicotinamide adenine dinucleotide adsorbed at nano-boehmite/water and nano-corundum/water interfaces.

In this study, the adsorption behaviors of nicotinamide adenine dinucleotide (NAD(+)) on nano-boehmite (γ-AlOOH) and nano-corundum (γ-Al(2)O(3)) surfaces were investigated. The results showed that NAD(+) was predominantly adsorbed at the boehmite/water and corundum/water interfaces in outer-sphere fashions by electrostatic interaction between NAD(+) phosphate and surface hydroxyl groups. However, the features of ATR-FTIR spectra suggested that some minor inner-sphere complex should be considered at low pH conditions on corundum surface, which was consistent with the effect of NAD(+) on dissolution rate of corundum. In addition, the adsorption data well fitted with Langmuir and Freundlich isotherms on the boehmite and corundum surfaces, respectively. Also, the Gibbs adsorption energy was negative on the boehmite surface, which indicated that the adsorption behavior was spontaneous.

Electrochemical and spectral study on the effects of Al(III) and nano-Al13 species on glutamate dehydrogenase activity.

A functionalized multi-wall nanotube (MWNT) modified glass carbon electrode (GCE) was used to study the effects of aluminum species on glutamate dehydrogenase (GLDH) activity by monitoring amperometric i-t curve for the oxidation of the enzymatically generated NADH. The conformational changes of the coenzyme nicotinamide adenine dinucleotide (NAD(+)) induced by Al(III) and nanometer-sized tridecameric aluminum polycation (nano-Al(13)) were investigated by the fluorescence technique. The results showed that the electrochemical method may be a potential tool to investigate the activity of enzymes in the biological system. It may also be useful in studying the effects of nano-sized aluminum compounds on biomolecules in order to discuss their safety to the environment and human.