Causal associations of antioxidants with Alzheimer's disease and cognitive function: a Mendelian randomisation study.

BACKGROUND: Circulating antioxidants are associated with a lower risk of Alzheimer's disease (AD) in observational studies, suggesting potential target areas for intervention. However, whether the associations are causal remains unclear. Here, we studied the causality between antioxidants and AD or cognitive function using two-sample Mendelian randomisation (MR). METHODS: Single nucleotide polymorphisms strongly (p<5×10-8) associated with antioxidants (vitamin A, vitamin C, zinc, selenium, ß-carotene and urate) and outcomes (AD, cognitive performance and reaction time) were obtained from the largest and most recent genome-wide association studies (GWAS). MR inverse variance weighting (IVW) and MR pleiotropy residual sum and outlier test (MR-PRESSO) were used for data analysis. RESULTS: Higher genetically determined selenium level was associated with 5% higher risk of AD (OR 1.047, 95% CI 1.005 to 1.091, p=0.028) using IVW. Higher genetically determined urate level was associated with worse cognitive performance (ß=-0.026, 95% CI -0.044 to -0.008, p=0.005) using MR-PRESSO. No association between the other antioxidants and AD, cognitive performance and reaction time was found. Similar results were found in the sensitivity analyses. CONCLUSION: Our results suggest that lifelong exposure to higher selenium may be associated with a higher risk of AD, and higher urate levels could be associated with worse cognitive performance. Further analyses using larger GWAS of antioxidants are warranted to confirm these observations. Our results suggest that caution is needed in the interpretation of traditional observational evidence on the neuroprotective effects of antioxidants.

Trifolirhizin protects ovariectomy-induced bone loss in mice by inhibiting osteoclast differentiation and bone resorption.

Background: Osteoporosis is a debilitating condition characterized by reduced bone density and microstructure, leading to increased susceptibility to fractures and increased mortality, particularly among older individuals. Despite the availability of drugs for osteoporosis treatment, the need for targeted and innovative agents with fewer adverse effects persists. Trifolirhizin, a natural pterostalin derived from the root of Sophora flavescens, has been previously studied for its effects on certain anticancer and antiinflammatory. The impact of trifolirhizin on the formation and function of osteoclasts remain unclear. Purpose: Herein, the possible roles of trifolirhizin the formation and function of osteoclasts and the underlying mechanism were explored. Methods: Bone marrow-derived macrophages (BMMs) were employed to evaluate the roles of trifolirhizin on steoclastogenesis, bone absorption and the underlying mechanism in vitro. Bone loss model was established by ovariectomy(OVX) in mice in vivo. Results: Trifolirhizin repressed osteoclastogenesis, bone resorption induced by receptor activator of nuclear factor kappa B ligand (RANKL) in vitro. Mechanistically, trifolirhizin inhibits RANKL-induced MAPK signal transduction and NFATc1 expression. Moreover, trifolirhizin inhibited osteoclast marker gene expression, including NFATc1, CTSK, MMP9, DC-STAMP, ACP5, and V-ATPase-D2. Additionally, trifolirhizin was found to protect against ovariectomy(OVX)-induced bone loss in mice. Conclusion: Trifolirhizin can effectively inhibit osteoclast production and bone resorption activity. The results of our study provide evidence for trifolirhizin as a potential drug for the prevention and treatment of osteoporosis and other osteolytic diseases.

Causal associations between polyunsaturated fatty acids and kidney function: A bidirectional Mendelian randomization study.

BACKGROUND: PUFAs were suggested to be beneficial for kidney function in observational studies. However, whether these associations are causal remains unclear. OBJECTIVES: This study explores the causality between PUFAs and chronic kidney disease (CKD) or estimated glomerular filtration rate (eGFR) using bidirectional 2-sample Mendelian randomization (MR). METHODS: Single nucleotide polymorphisms associated with PUFAs and kidney function were obtained from the largest and most recent genome-wide association studies with sample sizes of 13,544, 13,506, 13,499, 13,527, and 13,549 for omega-3 fatty acids, omega-6 fatty acids, DHA, LA, and other PUFAs than 18:2 (otPUFA), and 480,698 and 1,201,909 for CKD and eGFR, respectively. MR inverse-variance weighted (IVW) and pleiotropy residual sum and outlier test (MR-PRESSO) were used for data analysis, supplemented with a weighted median estimator, MR-Egger regression, and multivariable MR, giving ß or OR and their 95% CIs. RESULTS: There was suggestive evidence that higher omega-6 fatty acids were associated with increased eGFR using MR-PRESSO [ß: 0.005 log(mL/min/1.73 m2) per SD increase in omega-6 fatty acids; 95% CI: 0.002, 0.008; P = 0.008]. Higher LA level was also associated with higher eGFR [ß: 0.005 log(mL/min/1.73 m2) per SD increase in LA; 95% CI: 0.003, 0.007; P = 0.0007] using MR-PRESSO. Neither association of the other PUFAs, i.e., omega-3 fatty acids, DHA, and otPUFA, with CKD or eGFR nor the association of CKD and eGFR with PUFAs was found. Similar results were found in sensitivity analyses. CONCLUSIONS: Our results suggest that higher omega-6 fatty acids and LA may increase eGFR levels. Although the estimated effects were relatively small, the results provide public health and research relevance, indicating the need for further longitudinal cohorts or randomized controlled trials on omega-6 fatty acids in improving kidney function.

Brevilin A inhibits RANKL-induced osteoclast differentiation and bone resorption.

Brevilin A (BA) is the primary component of Centipeda minima, which is widely used in Chinese traditional medicine. The anti-inflammatory and anti-tumor properties of BA have been established; however, its function in bone metabolism is not well understood. This study revealed that concentrations of BA below 1.0 µM did not inhibit the proliferation of bone marrow macrophages but did impede the differentiation and bone resorption activity of osteoclasts. Furthermore, BA suppressed the expression of osteoclast-specific genes Mmp9, Acp5, Dc-stamp, Ctsk, and Atp6v0d2. In addition, mTOR, ERK, and NFATc1 activation in bone marrow macrophages were suppressed by BA. As a whole, BA blocks the mTOR and ERK signaling pathways, which is responsible for the development and activity of osteoclasts, and the resorption of bone.

Loss of E-cadherin promotes the growth, invasion and drug resistance of colorectal cancer cells and is associated with liver metastasis.

The recent studies indicated that the epithelial cell adhesion molecule E-cadherin is a well-recognized molecule that is important in cell adhesion. To further investigate the molecular basis of this notion, we used small-interfering RNA to inhibit E-cadherin function and found that loss of E-cadherin promoted Colorectal cancer cell growth, invasion and drug resistance through induction of ß-catenin nuclear translocation and epithelial-to-mesenchymal transition. Further analysis of E-cadherin expression with clinicopathologic parameters showed that E-cadherin expression decreased in Colorectal cancer patients who developed liver metastasis (P = 0.043). These findings indicate that E-cadherin loss in tumors contributes to progression and metastatic dissemination. Thus, E-cadherin can act as a central modulator of the cell biological phenotypes and a potential prognostic marker in Colorectal cancer.

Plasma polyunsaturated fatty acid concentrations and sleep apnea risk: A two-sample Mendelian randomization study.

Background: Previous observational studies have found that lower levels of circulating polyunsaturated fatty acids (PUFAs) were associated with a higher risk of sleep apnea (SA). However, the causality of the association remains unclear. Materials and methods: We used the two-sample Mendelian randomization (MR) study to assess the causal association of omega-3 and omega-6 fatty acids with SA. Single-nucleotide polymorphisms (SNPs) predicting the plasma level of PUFAs at the suggestive genome-wide significance level (p < 5 × 10-6) were selected as instrumental variables (IVs) from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) (n = ∼8,000) Consortium. For outcomes, the summary-level statistics of SA were obtained from the latest genome-wide association study (GWAS), which combined five cohorts with a total number of 25,008 SA cases and 172,050 snoring cases (total = 523,366). Results: We found no association of α-linolenic acid (ALA) [odds ratio (OR) = 1.09 per% changed, 95% confidence interval (CI) 0.67-1.78], eicosapentaenoic acid (EPA) (OR = 0.94, 95% CI 0.88-1.01), docosapentaenoic acid (DPA) (OR = 0.95, 95% CI 0.88-1.02), and docosahexaenoic acid (DHA) (OR = 0.99, 95% CI 0.96-1.02) with the risk of SA using inverse-variance weighted (IVW) method. Moreover, for omega-6 PUFAs, no association between linoleic acid (LA) (OR = 0.98, 95% CI 0.96-1.01), arachidonic acid (AA) (1.00, 95% CI 0.99-1.01), and adrenic acid (AdrA) (0.93, 95% CI 0.71-1.21) with the risk of SA was found. Similarly, no associations of PUFAs with SA were found in single-locus MR analysis. Conclusion: In the current study, we first found that there is no genetic evidence to support the causal role of omega-3 and omega-6 PUFAs in the risk of SA. From a public health perspective, our findings refute the notion that consumption of foods rich in PUFAs or the use of PUFAs supplementation can reduce the risk of SA.

Detection of Bacterial Metabolic Volatile Indole Using a Graphene-Based Field-Effect Transistor Biosensor.

The existence of bacteria is a great threat to food safety. Volatile compounds secreted by bacteria during their metabolic process can be dissected to evaluate bacterial contamination. Indole, as a major volatile molecule released by Escherichia coli (E. coli), was chosen to examine the presence of E. coli in this research. In this work, a graphene field-effect transistor (G-FET) was employed to detect the volatile molecule-indole based on a π-π stacking interaction between the indole and the graphene. The exposure of G-FET devices to the indole provokes a change in electrical signal, which is ascribed to the adsorption of the indole molecule onto the graphene surface via π-π stacking. The adsorption of the indole causes a charge rearrangement of the graphene-indole complex, which leads to changes in the electrical signal of G-FET biosensors with a different indole concentration. Currently, the indole biosensor can detect indole from 10 ppb to 250 ppb and reach a limit of detection of 10 ppb for indole solution detection. We believe that our detection strategy for detecting bacterial metabolic gas molecules will pave a way to developing an effective platform for bacteria detection in food safety monitoring.

Native useful vascular plants of China: A checklist and use patterns.

Of all types of interactions between humans and plants, the utilization of plants by people is the most direct and influential. China has a long history of using native plants and a large body of recorded knowledge on uses. Here, we present an inventory of plant uses in China based on an extensive survey of the literature. Twelve categories of usage are recognized (medicinal, edible, etc.), these categories being chosen according to an integration of various current standards. A total of 50,521 use-citations were recorded, covering 10,808 species and infraspecies, representing 28% of the Chinese flora. Additional information is included in the dataset on taxonomy and endangerment status. Analysis of the data reveals that the eight plant families with the greatest numbers of species used in China, namely Asteraceae, Fabaceae, Rosaceae, Ranunculaceae, Poaceae, Lamiaceae, Orchidaceae, and Liliaceae, are also the top eight most species-rich Chinese plant families. However, there are some families that are over-represented or under-representation in certain use categories, compared with their relative abundance in the total flora. There are indications that rare and endangered species are being subject to some degree of over-exploitation. A disproportionately high number of used species are Chinese endemics (3552 species, representing over 33% of used species). A total of 20% of used species have been classified as threatened nationally or globally, according to at least one of the various threat assessments that have been made for the Chinese flora. This comprehensive inventory of the useful plants of China, with relevant ethnobotanical information included, provides a baseline for further studies of plant resources. It will be useful in follow-up research. The scientific dataset it contains will be useful for the protection and sustainable utilization of plant resources in China.

Ostracism, Psychological Capital, Perceived Social Support and Depression among Economically Disadvantaged Youths: A Moderated Mediation Model.

Mental health promotion of economically disadvantaged youths is a popular issue in current China. Economically disadvantaged youths are at greater risk of depression. Ostracism may be an important predictor of depression for them. However, no consensus has been reached on the underlying mechanism between ostracism and depression. A total of 1207 economically disadvantaged youths were recruited from six universities in China. These youths were asked to complete questionnaires measuring depression, ostracism, psychological capital, and perceived social support. A moderated mediation model was examined by using IBM SPSS STATISTICS 27macro program PROCESS version 3.5, in which psychological capital was a mediating variable, and perceived social support was a moderating variable. Lack of causal inferences and self-report bias due to the cross-sectional and self-report survey need to be considered when interpreting results. The results revealed that ostracism was positively associated with depression among economically disadvantaged youths. Psychological capital partially mediated the association. Perceived social support moderated the indirect association between ostracism and depression via psychological capital among economically disadvantaged females. Training and intentional practice of psychological capital could be the core to develop the depression interventions targeting economically disadvantaged youths with experience of ostracism. Gender and perceived social support need to be considered in developing the interventions.

6'-O-Galloylpaeoniflorin Attenuates Osteoclasto-genesis and Relieves Ovariectomy-Induced Osteoporosis by Inhibiting Reactive Oxygen Species and MAPKs/c-Fos/NFATc1 Signaling Pathway.

Emerging evidence suggests bright prospects of some natural antioxidants in the treatment of osteoporosis. 6'-O-Galloylpaeoniflorin (GPF), an antioxidant isolated from peony roots (one of very widely used Oriental medicines, with various anti-inflammatory, antitumor, and antioxidant activities), shows a series of potential clinical applications. However, its effects on osteoporosis remain poorly investigated. The current study aimed to explore whether GPF can attenuate osteoclastogenesis and relieve ovariectomy-induced osteoporosis via attenuating reactive oxygen species (ROS), and investigate the possible mechanism. After the culture of primary murine bone marrow-derived macrophages/monocytes were induced by the use of macrophage colony-stimulating factor (M-CSF) and the receptor activator of NF-κB ligand (RANKL) and then treated with GPF. Cell proliferation and viability were assessed by Cell Counting Kit-8 (CCK-8) assay. Thereafter, the role of GPF in the production of osteoclasts and the osteogenic resorption of mature osteoclasts were evaluated by tartrate-resistant acid phosphatase (TRAP) staining, podosome belt formation, and resorption pit assay. Western blotting and qRT-PCR examination were performed to evaluate proteins' generation and osteoclast-specific gene levels, respectively. The ROS generation in cells was measured in vitro by 2',7'-Dichlorodi-hydrofluorescein diacetate (DCFH-DA). Ovariectomy-induced osteoporosis mouse administered with GPF or vehicle was performed to explore the in vivo potential of GPF, then a micro-CT scan was performed in combination with histological examination for further analysis. GPF suppressed the formation of osteoclasts and podosome belts, as well as bone resorption when induced by RANKL through affecting intracellular ROS activity, MAPKs signaling pathway, and subsequent NFATc1 translocation and expression, as well as osteoclast-specific gene expression in vitro. In vivo study suggested that exposure to GPF prevented osteoporosis-related bone loss in the ovariectomized mice. These findings indicate that GPF attenuates osteoclastogenesis and relieves ovariectomy-induced osteoporosis by inhibiting ROS and MAPKs/c-Fos/NFATc1 signaling pathway. This suggested that GPF may be potentially used to treat bone diseases like periodontitis, rheumatoid arthritis, and osteoporosis associated with osteoclasts.

Spleen tyrosine kinase (SYK) inhibitor PRT062607 protects against ovariectomy-induced bone loss and breast cancer-induced bone destruction.

Osteolytic diseases, including breast cancer-induced osteolysis and postmenopausal osteoporosis, are attributed to excessive bone resorption by osteoclasts. Spleen tyrosine kinase (SYK) is involved in osteoclastogenesis and bone resorption, whose role in breast cancer though remains controversial. Effects of PRT062607 (PRT), a highly specific inhibitor of SYK, on the osteoclast and breast cancer functionalities are yet to be clarified. This study demonstrated the in vitro inhibitory actions of PRT on the osteoclast-specific gene expression, bone resorption, and osteoclastogenesis caused by receptor activator of nuclear factor kappa B ligand (RANKL), as well as its in vitro suppressive effects on the growth, migration and invasion of breast carcinoma cell line MDA-MB-231, which were achieved through PLCγ2 and PI3K-AKT-mTOR pathways. Further, we proved that PRT could prevent post-ovariectomy (OVX) loss of bone and breast cancer-induced bone destruction in vivo, which agreed with the in vitro outcomes. In conclusion, our findings suggest the potential value of PRT in managing osteolytic diseases mediated by osteoclasts.

MicroRNA-141 regulates Smad interacting protein 1 (SIP1) and inhibits migration and invasion of colorectal cancer cells.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer in the world. Despite recent advances in diagnostics and treatment, prognosis for patients with advanced disease is still poor. microRNAs (miRNAs) are a class of endogenous, small noncoding RNA molecules which are crucial regulators of gene expression at the posttranscriptional level. miRNAs participate in many biological events and play an important role in various human diseases, including CRC. AIMS: This study is to identify the role of miR-141 in migration and invasion of CRC cells. METHODS: Expression of miR-141 and Smad interacting protein 1 (SIP1) were detected by real-time reverse-transcription polymerase chain reaction (RT-PCR) and Western blotting. The effect of miR-141 on migration and invasion of CRC cells was investigated using wound healing assay and Matrigel invasion assay in vitro. The regulation effect of miR-141 on SIP1 was evaluated by dual-luciferase reporter assay. RESULTS: We demonstrated that miR-141 levels correlate inversely with SIP1 protein levels as well as cell migration and invasion of CRC cells. SIP1 was identified as a functional target of miR-141. CONCLUSIONS: miR-141 regulates SIP1 to inhibit migration and invasion of CRC cells. miR-141 and SIP1 might be candidate therapeutic targets in CRC.

Reversible reconfiguration of high-order DNA nanostructures by employing G-quartet toeholds as adhesive units.

G-quadruplex structures are becoming useful alternative interaction modules for the assembly of DNA nanomaterials because of their unique inducibility by cations. In this study, we demonstrated a new strategy for the assembly of polymeric DNA nanoarchitectures in the presence of cations, such as K+ and Na+, by employing G-quartet toeholds at the edges of discrete mini-square DNA building blocks as adhesive units. In comparison with the Watson-Crick base-paired duplex linkers, G-quadruplex arrays embedded in the self-assembled DNA system exhibit higher thermal stability. The morphology of these doughnut-shaped or spherical-shaped DNA nanostructures is highly regulated by the orientation of the folded G-quadruplexes either in parallel or antiparallel orientation in response to different cations. Furthermore, this G-quadruplex-mediated assembly strategy is able to manipulate the cycling of DNA assemblies between discrete and polymeric states by means of introducing cations and chelating agents sequentially. This property enables the reversible manipulation of the DNA-based nanosystems for at least 4 cycles. The G-quadruplex array embedded in this self-assembled DNA system can become a scaffold for functional molecules, as a number of organic molecules and proteins exhibit specific binding to these G-quadruplex structures. Besides, embedded G-quadruplexes are also considered as functional components of nanoscale electronic materials due to their electron transport through the stacked orientation of the G-quartet. Therefore, this work is an important step towards obtaining reversible, responsive G-quadruplex-induced DNA-based nanomaterials with versatile functionalities which will be highly useful in further electronic, biomedical and drug-delivery applications.

[Study on effect of sho-saiko-to compound on growth of nasopharyngeal carcinoma cells in CNE-bearing nude mice].

OBJECTIVE: To investigate the role of sho-saiko-to compound (SSTC) on the growth of the well-differentiated squamous cell line 1 of nasopharyngeal carcinoma (CNE-1) and well-differentiated CNE-2 in tumor-bearing nude mouse, and try to supply scientific data for its clinical development. METHOD: SSTC were prepared by concentration gradients, and the effect of SSTC on the growth and proliferation of the CNE-1 and CNE-2 were investigated by MT assay and soft-agar colony formation test. After setting up the subcutaneous tumor-bearing nude mouse model at the right lower back (0.2 mL CNE-2 cell suspension, 5 x 10(5)/mL), we randomly divided forty mice into 5 groups and gave high, middle and low concentration groups of SSTC (0.5, 0.25, 0.125 g X mL(-1) by intragastric administration. Positive and negative groups were set up for comparison. After constant administration for 15 days, the volume and weight of the tumor were measured for inhibition rate, so as to investigate the role of SSTC on the CNE-2 bearing tumor. RESULT: In vitro, compared with negative control, SSTC at different gradient concentrations were cultured with the CNE-1 and CNE-2 for 24 h, 48 h and 72 h. It showed that the growth and proliferation of both cell lines were inhibited to some extent. The inhibition rate was increased as the concentration and culture time increasing. Both MTT assay and soft-agar colony formation test showed that the 50% inhibiting concentration (IC50) was about 2.5 g X L(-1). In vivo, compared with negative control, the SSTC could slow down the tumor growth in the SSTC treated groups. The tumor growth of the negative control group (0.76 +/- 0.28) g, (962.88 +/- 245.96) mm3 and the low concentration group of SSTC (0.88 +/- 0.40) g, (1239.66 +/- 421.93) mm3 were obviously faster than those of the high, middle concentration group of SSTC (0.22 +/- 0.14) g, (239.31 +/- 137.07) mm3; (0.20 +/- 0.16) g, (263.42 +/- 166.57) mm3 and CTX positive control group (0.20 +/- 0.10) g, (246.72 +/- 194.6) mm3 (P<0.05). CONCLUSION: SSTC could efficiently inhibit the growth and proliferation of CNE-1 and CNE-2 in vitro, and slow down the tumor growth of the CNE-2 bearing nude mice. It may be a new compound of Chinese medicine for nasopharyngeal carcinoma therapy.

Graphene Field-Effect Transistors for the Sensitive and Selective Detection of Escherichia coli Using Pyrene-Tagged DNA Aptamer.

This study reports biosensing using graphene field-effect transistors with the aid of pyrene-tagged DNA aptamers, which exhibit excellent selectivity, affinity, and stability for Escherichia coli (E. coli) detection. The aptamer is employed as the sensing probe due to its advantages such as high stability and high affinity toward small molecules and even whole cells. The change of the carrier density in the probe-modified graphene due to the attachment of E. coli is discussed theoretically for the first time and also verified experimentally. The conformational change of the aptamer due to the binding of E. coli brings the negatively charged E. coli close to the graphene surface, increasing the hole carrier density efficiently in graphene and achieving electrical detection. The binding of negatively charged E. coli induces holes in graphene, which are pumped into the graphene channel from the contact electrodes. The carrier mobility, which correlates the gate voltage to the electrical signal of the APG-FETs, is analyzed and optimized here. The excellent sensing performance such as low detection limit, high sensitivity, outstanding selectivity and stability of the graphene biosensor for E. coli detection paves the way to develop graphene biosensors for bacterial detection.

In Situ Probing the Relaxation Properties of Ultrathin Polystyrene Films by Using Electric Force Microscopy.

The rapid development of nanoscience and nanotechnology involves polymer films with thickness down to nanometer scale. However, the properties of ultrathin polymer films are extremely different from that of bulk matrix or thin films. It is challenging to distinguish the changes of physical properties in ultrathin films using conventional techniques especially when it locates near the glass transition temperature (T g). In this work, we successfully evaluated a series of physical properties of ultrathin polystyrene (PS) films by in situ characterizing the discharging behavior of the patterned charges using electric force microscopy. By monitoring the surface potential in real time, we found that the T g of ultrathin PS films is clearly independent of film thickness, which are greatly different from that of thin PS films (film thickness larger than 10 nm).

A femtosecond transient absorption study of charge photogeneration and recombination dynamics in photovoltaic polymers with different side-chain linkages.

A pair of 9-arylidene-9H-fluorene and benzothiadiazole based, low-bandgap copolymers differing merely in the para or meta substitution of alkoxy groups to the arylidene linkages, i.e. p-PAFDTBT and m-PAFDTBT respectively, were comparatively investigated by using morphological characterization, ultrafast spectroscopy and quantum chemical calculations. Despite the subtle difference in the alkoxy substitution patterns, p-PAFDTBT molecules in photoactive films were shown to have a higher degree of crystallinity owing to the relatively less rotational torsion of the arylidene linkages. As a result, in either neat or fullerene-blended films, p-PAFDTBT compared to m-PAFDTBT gave rise to a substantially higher charge yield and much slower charge recombination. This work demonstrates that the alkoxy substitution pattern and the arylidene linkage are highly influencing on the morphology of the photoactive layers and thereby on the photovoltaic performance of the semiconducting copolymers.

Chondrogenic differentiation of ATDC5 and hMSCs could be induced by a novel scaffold-tricalcium phosphate-collagen-hyaluronan without any exogenous growth factors in vitro.

Application of chondrogenic growth factors is a routine strategy to induce chondrogenesis of hMSCs, but they have economic and safety problems in the long term. It is expected that scaffold material itself could play an important role in chondrogenesis of hMSCs. In this study we tested whether a novel tricalcium phosphate-collagen-hyaluronan scaffold (TCP-COL-HA) had inherent chondro-inductive capacity for chondrogenesis of both ATDC5 and hMSCs without any exogenous growth factors in vitro. hMSCs and ATDC5 were seeded onto TCP-COL-HA scaffolds and cultured in basal medium for 3 weeks to investigate whether the TCP-COL-HA scaffold itself had differentiation-inductive capacity in basal culture. With hMSCs-seeded scaffold in chondrogenic medium (including TGF-ß1) as positive control, we then compared the chondrogenic induction of TCP-COL-HA in basal culture and in chondrogenic culture. The chondrogenic differentiation was evaluated by sulfated glycosaminoglycans (GAGs) quantification, type II collagen immunohistochemistry, and RT-PCR. Mechanical strength was evaluated by compression test and the cell death rate of hMSCs was assessed with TUNEL assay. The results showed TCP-COL-HA scaffold itself could efficiently induce chondrogenic differentiation of both ATDC5 and hMSCs after 3 weeks in basal culture. The accumulation of GAGs and the expression of chondrocyte marker genes were all significantly increased. In addition, hMSCs-seeded scaffold showed a significantly higher mechanical strength after 3 weeks in basal culture. The chondrogenic induction of TCP-COL-HA scaffolds in basal medium were almost similar to that in chondrogenic medium on hMSCs. The chondrogenesis-inducing capacity of TCP-COL-HA scaffold might help to improve cartilage tissue engineering with economic and safe benefits.

Phosphatidylserine enhances osteogenic differentiation in human mesenchymal stem cells via ERK signal pathways.

Phosphatidylserine (PS) has been demonstrated to promote bone mineralization. It has also been used in bone repairing biomaterials as a functional molecule. However, the effect of PS on mesenchymal stem cells (MSCs) is not clear. In this study, we determined the effect of PS on the osteogenic differentiation of human MSCs (hMSCs) cultured in growth or osteogenic differentiation medium and the role of the ERK1/2 signaling pathway on PS activity. Cytotoxicity of PS was measured by MTT assay in growth medium for 5 days. Cell osteogenic differentiation was evaluated by alkaline phosphatase (ALP) activity analysis, Alizarin Red S staining and real-time PCR assay. Western blotting and ERK blocking assay were used to examine the role of ERK1/2 signaling pathway on PS activity. The results showed no cytotoxicity for the doses of PS administered. For 21 days, 50-100 µM PS increased ALP expression and mineralization of hMSCs. The expression of the osteogenic gene marker, ALP, osteocalcin (OC), and RUNX2 was enhanced by 50 µM PS treatment at day 14. Phospho-ERK was activated by 50 µM PS at 30 min and 1h in growth medium. In osteogenic medium, 50 µM PS extended phospho-ERK activation by osteogenic induction medium from 30 min to 8 h. U0126, an ERK inhibitor, suppressed the ALP expression induced by PS. Our data indicate that the ERK signal is potentially a mediator in the process of osteogenic differentiation of hMSCs induced by PS. PS, as a functional molecule, has high potential for use in bone repairing biomaterials and bone tissue engineering.

[Development of the role of micrornas regulation in osteogenesis].

OBJECTIVE: To review the progress, controversy and trend in the regulation and mechanism of the microRNAs (miRNAs) during the osteogenesis. METHODS: Recent literature concerning regulation and mechanism of the miRNAs during the osteogenesis was extensively reviewed, summarized and analyzed. RESULTS: Recently miRNAs was a hot topic for osteogenesis. More and more materials showed its important role in ossification, but its definite mechanism was not clear. CONCLUSION: Osteogenesis can be strengthened by miRNAs technology, which has a bright future and may also provide the molecular mechanism. The study on miRNAs of osteogenesis can provide a model to analyze and compare the osteogenetic effects of novel drugs.