A novel Mn(2+)-doped core/shell quantum dot-based intracellular probe for fluoride anions sensing in MC3T3-E1 osteoblastic cells.

In this paper, 3-aminobenzeneboronic acid functionalized Mn(2+)-doped ZnTe/ZnSe quantum dots (APBA-dQDs) were prepared. The APBA functional groups had strong binding ability with F(-), resulting in the quenchment of dQDs photoluminescence (PL). Under the optimal condition, the fluorescence intensity of APBA-dQDs was related linearly to the concentration of F(-) in the range of 0.25-1.5µmol/L with a detection limit of 0.1µmol/L. The selectivity of fluorescence quenching of APBA-dQDs for F(-) was enhanced. Moreover, the proposed methodology for the sensing of F(-) at EM 560nm in MC3T3-E1 osteoblastic cells was demonstrated and got a satisfactory results. The results indicate that the APBA-dQDs are promising candidates for intracellular in MC3T3-E1 osteoblastic cells. To the best of our knowledge, it was the first report of F(-) sensing by using the quenched fluorescence of APBA-dQDs in non-cancerous cells.

Mechanisms of Intracellular Calcium Homeostasis in MC3T3-E1 Cells and Bone Tissues of Sprague-Dawley Rats Exposed to Fluoride.

Calcium homeostasis of osteoblasts (OBs) has an important role in the physiology and pathology of bone tissue. In order to study the mechanisms of intracellular calcium homeostasis, MC3T3-E1 cells and Sprague-Dawley rats were treated with different concentrations of fluoride. Then, we examined intracellular-free calcium ion ([Ca(2+)]i) in MC3T3-E1 cells as well as mRNA and protein levels of Cav1.2, the main subunit of L-type voltage-dependent calcium channels (VDCCs), Na(+)/Ca(2+) exchange carriers (NCS), and plasma membrane Ca(2+)-ATPase (PMCA), inositol 1,4,5-trisphosphate receptor (IP3R) channels, sarco/endoplasmic reticulum calcium ATPase 2b (SERCA2b)/ATP2A2 in vitro, and rat bone tissues in vivo. Our results showed that [Ca(2+)]i of fluoride-treated OBs increased in a concentration-dependent manner with an increase in the concentration of fluoride. We also found that the low dose of fluoride led to high expression levels of Cav1.2, NCS-1, and PMCA and low expression levels of IP3R and SERCA2b/ATP2A2, while the high dose of fluoride induced an increase in SERCA2b/ATP2A2 levels and decrease in Cav1.2, PMCA, NCS-1, and IP3R levels. These results demonstrate that calcium channels and calcium pumps of plasma and endoplasmic reticulum (ER) membranes keep intracellular calcium homeostasis by regulating Cav1.2, NCS-1, PMCA, IP3R, and SERCA2b/ATP2A2 expression.

Fluoride Affects Calcium Homeostasis by Regulating Parathyroid Hormone, PTH-Related Peptide, and Calcium-Sensing Receptor Expression.

Parathyroid hormone (PTH), PTH-related peptide (PTHrP), and calcium-sensing receptor (CaSR) play important roles in maintaining calcium homeostasis. Here, we study the effect of fluoride on expression of PTH, PTHrP, and CaSR both in vitro and in vivo. MC3T3-E1 cells and Sprague-Dawley rats were treated with different concentrations of fluoride. Then, the free calcium ion concentration in cell culture supernatant and serum were measured by biochemical analyzer. The expression of PTH, PTHrP, and CaSR was analyzed by qRT-PCR and Western blot. We found that the low dose of fluoride increased ionized calcium (i[Ca(2+)]) and the high dose of fluoride decreased i[Ca(2+)] in cell culture supernatant. The low dose of fluoride inhibited the PTH and PTHrP expression in MC3T3-E1 cells. The high dose of fluoride improved the PTHrP expression in MC3T3-E1 cells. Interestingly, we found that NaF decreased serum i[Ca(2+)] in rats. Fluoride increased CaSR expression at both messenger RNA (mRNA) and protein levels in MC3T3-E1 cells and rats. The expression of PTHrP protein was inhibited by fluoride in rats fed regular diet and was increased by fluoride in rats fed low-calcium diet. Fluoride also increased the expression of PTH, NF-kappaB ligand (RANKL), and osteoprotegerin (OPG) in rats. The ratio of RANKL/OPG in rats fed low-calcium food in presence or absence of fluoride was significantly increased. These results indicated that fluoride might be able to affect calcium homeostasis by regulating PTH, PTHrP, and CaSR.

The impact of self-concept and college involvement on the first-year success of medical students in China.

Students' first-year academic success plays a critical role on their overall development in college, which implies the need to concentrate on identifying ways to improve students' first-year academic success. Different from most research on the subject, this study attempted to combine the sociological perspective of college impact with a psychological perspective to synthetically explore the causal relationship of specific types of self-concept and college involvement with academic success of medical students. A longitudinal study was conducted using 519 matriculates at a medical university in mainland China. We conducted the Cooperative Institutional Research Program freshmen survey and the Your First College Year survey to collect data of the pre-college and college academic and social self-concept, college involvement components, and some input characteristics. The academic success was measured by the first-year grade point average. A pathway analysis was conducted and showed the following results. Having high academic self-concept, being engaged in class and putting effort in homework or study directly contributes to increasing college achievement. Students' pre-college achievement and self-concept, faculty interaction, and homework involvement positively affected students' college academic self-concept development, which indirectly improved average grade point. These findings contribute to our understanding of a student's ability to interact with his or her collegiate environment and to experience academic success.

Fluoride affects calcium homeostasis and osteogenic transcription factor expressions through L-type calcium channels in osteoblast cell line.

Osteoblast L-type voltage-dependent calcium channels (VDCC) play important roles in maintaining intracellular homeostasis and influencing multiple cellular processes. In particular, they contribute to the activities and functions of osteoblasts (OBs). In order to study how L-type VDCC modulate calcium ion (Ca(2+)) homeostasis and the expression of osteogenic transcription factors in OBs exposed to fluoride, MC3T3-E1 cells were exposed to a gradient of concentrations of fluoride (0, 2.0, 5.0, 10.0 mg/L) in combination with 10 µM nifedipine, a specific inhibitor of VDCC, for 48 h. We examined messenger RNA (mRNA) and protein levels of Cav1.2, the main subunit of VDCC, and c-fos, c-jun, runt-related transcription factor 2 (Runx2), osterix (OSX), and intracellular free Ca(2+) ([Ca(2+)]i) concentrations in MC3T3-E1 cells. Our results showed that [Ca(2+)]i levels increased in a dose-dependent manner with increase in concentration of fluoride. Meantime, results indicated that lower concentrations of fluoride (less than 5 mg/L, especially 2 mg/L) can lead to high expression of Cav1.2 and enhance osteogenic function, while high concentration of fluoride (10 mg/L) can induce decreased Cav1.2 and osteogenic transcriptional factors in MC3T3E1 cells exposed to fluoride. However, the levels of [Ca(2+)]i, Cav1.2, c-fos, c-jun, Runx2, and OSX induced by fluoride were significantly altered and even reversed in the presence of nifedipine. These results demonstrate that L-type calcium channels play a crucial role in Ca(2+) homeostasis and they affect the expression of osteogenic transcription factors in fluoride-treated osteoblasts.

Predictors of first-year GPA of medical students: a longitudinal study of 1285 matriculates in China.

BACKGROUND: Although medical education has developed rapidly in the last decade, and the National College Entrance Examination (NCEE) is used as the "gold standard" for admission to medical college in mainland China, there is a lack of literature regarding the influence of NCEE score and other factors on the academic performance of medical students. This study aimed to examine potential predictors of first-year grade point average (GPA) for medical students. METHODS: This study included 1,285 students who matriculated at a first-tier medical university in mainland China in 2011. The precollege motivational attitudes for each matriculate were investigated via questionnaire. A hierarchical linear model was fitted to regress first-year GPA on a 100-point scale on NCEE score and other student-level and major-level characteristics. RESULTS: NCEE score was a significant predictor of both within-major and between-major variation of first-year GPA for medical students. Majors with higher mean NCEE scores had higher mean GPAs, and higher GPAs were observed among those individuals with higher NCEE scores after controlling for major-level characteristics. First-year GPA differed by certain individual socio-demographic variables. Female students had a 2.44-higher GPA on average than did male students. NCEE repeaters had a 1.55-lower GPA than non-repeaters. First-year GPA was associated negatively with parental income but positively with academic self-concept. CONCLUSIONS: NCEE score is an important predictor of the first-year GPA of medical students, but it is not the sole determinant. Individual socio-demographic characteristics and major-level characteristics should be taken into account to understand better and improve the first-year GPA of medical students.

Fluoride-induced oxidative stress in three-dimensional culture of OS732 cells and rats.

Exposure to excessive fluoride poses a threat to human health, including increased susceptibility to developing the skeletal fluorosis. Despite its recognized importance as an endemic disease, little is known about how fluoride directly impacts on osteoblasts. We previously reported that fluoride-stimulating monolayer-cultured osteoblast proliferation or inhibiting cell viability depended on fluoride-exposure concentration and period, both accompanied with active oxidative stress. The purpose of this study was to provide extra insight into skeletal fluorosis by comparing their regulation of oxidative stress in rats and OS732 cells (a human osteoblast-like cell line) cultured in the three-dimensional approach. Our in vivo and in vitro studies proved that exposure to fluoride promoted varying extents of oxidative stress. Three-dimensional cultured OS732 cells revealed the action of fluoride on cell viability from excitatory to inhibitory trend according to fluoride-exposure concentration and time. The study provided insight into the mechanism of skeletal fluorosis. Also, this study distinguished itself by identifying oxidative stress as a potential modulator of osteogenesis in skeletal fluorosis.

Role of oxidative stress in osteoblasts exposed to sodium fluoride.

We investigated the relationship between oxidative stress and osteoblasts viability in osteoblasts exposed to various concentrations of fluoride in this study. Primary calvarial osteoblasts from neonatal Kunming mice were cultured and subcultured to the third generation. Osteoblasts were incubated with sodium fluoride (0, 0.5, 1, 2, 4, 8, 12, and 20 mgF(-)/L) for 24, 48, and 72 h. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) analysis showed cell viability significantly increased after osteoblasts exposed to low concentrations of fluoride (0.5 to approximately 2 mgF(-)/L) for 24 to approximately 72 h. Oxidative stress analysis showed that low concentration of fluoride excited lipid peroxidation in osteoblasts and increased activity of antioxidant enzymes in varying degrees. We demonstrated that changes of osteoblasts viability of the low-dose fluoride groups are different from those of high-dose fluoride groups; however, both low and high doses of fluoride caused active state of oxidative stress in osteoblasts, which suggesting that oxidative stress may be excited by the active osteoblasts viability induced by a low dose of fluoride.

Coxsackievirus B3 infection and its mutation in Keshan disease.

AIM: To investigate coxsackievirus B(3) infection and its gene mutation in Keshan disease. METHODS: The expression of Coxsackievirus B(3) RNA was detected in autopsy specimens of acute (12 cases), sub-acute (27 cases) and chronic (15 cases) Keshan disease by in situ hybridization. In sub-acute Keshan disease specimens, 3 cases with positive result by in situ hybridization were selected RT-PCR analysis. The DNA segments were then sequenced. RESULTS: Coxsackievirus B(3) RNA was detected in the cytoplasm of myocardiocyte. The positive rate was 83% in acute, 67% in sub-acute and 80% in chronic Keshan disease. In the conservative region of Coxsackievirus B(3) genome, there was a mutation in 234 (C-T) compared to the non-cardiovirulent strain, CVB(3/0). CONCLUSION: Coxsackievirus B(3) RNA can survive and replicate in heart muscle of Keshan disease, which may play an important role in the occurrence of Keshan disease. The possible mechanism of occurrence of Keshan disease is associated with point a mutation in Coxsackievirus B(3) genome.

[Comparative study on anti-hypercholesterolemia activity of diosgenin and total saponin of Dioscorea panthaica].

OBJECTIVE: To compare the anti-hypercholesterolemic and cholesterol absorption inhibitory activities between total saponin of Dioscorea panthaica (TSDP) and diosgenin (Dio). METHOD: TSDP and Dio were given ig or i.p. to mice or rats treated with cholesterol feed to evaluate their preventive and therapeutic effect on hypercholesterolemia. TSDP or Dio and cholesterol were mixed with pig bile to form the micelle, then the freeing cholesterol was detected to evaluate inhibitory effect of the both compounds on cholesterol absorption. RESULT: Dio (80 and 160 mg.kg-1) showed significantly therapeutic and preventive effect on hypercholesterolemia in mice, while TSDP showed a certain preventive activity only at a big dose (400 mg.kg-1). The intraperitoneal injection of Dio (20 and 40 mg.kg-1) to mice suffered from hypercholesterolemia was effective, but TSDP showed no effective. The serum total cholesterol level was decreased when rats were pre-treated with TSDP (200 and 400 mg.kg-1, ig) and Dio (200 and 100 mg.kg-1, ig). However, the hypercholesterolemia-preventing activity of Dio was stronger than that of TSDP. In addition, inhibitory effect of Dio on cholesterol micelle formation was still stronger than that of TSDP. CONCLUSION: The preventive and therapeutic activity of Dio against hypercholesterolemia indused by cholesterol in mice or rats is stronger than that of TSDP. The anti-hypercholesterolemia mechanism of Dio is probably related with its cholesterol absorption inhibitory activity.