Trajectory and Sway Prediction Towards Fall Prevention.

Falls are the leading cause of fatal and non-fatal injuries, particularly for older persons. Imbalance can result from the body's internal causes (illness), or external causes (active or passive perturbation). Active perturbation results from applying an external force to a person, while passive perturbation results from human motion interacting with a static obstacle. This work proposes a metric that allows for the monitoring of the persons torso and its correlation to active and passive perturbations. We show that large changes in the torso sway can be strongly correlated to active perturbations. We also show that we can reasonably predict the future path and expected change in torso sway by conditioning the expected path and torso sway on the past trajectory, torso motion, and the surrounding scene. This could have direct future applications to fall prevention. Results demonstrate that the torso sway is strongly correlated with perturbations. And our model is able to make use of the visual cues presented in the panorama and condition the prediction accordingly.

A novel signature constructed by differential genes of muscle-invasive and non-muscle-invasive bladder cancer for the prediction of prognosis in bladder cancer.

Background: Bladder cancer (BCa) is a malignant tumor that usually forms cancer cells in the inner lining of the bladder. Hundreds of thousands of people worldwide have BCa diagnosed each year. The purpose of this study was to construct a prognostic model by differential expression of genes between muscular and non-muscular invasive BCa, and to investigate the prognosis of BCa patients. Methods: The data of BCa patients was sourced from the GEO and TCGA database. Single-cell sequencing data was obtained from three patients in the GSE135337 database, and microarray data for verification was obtained from GSE32894. Univariate, Lasso and multivariate cox regression analyses were performed to construct the prognostic model. The prognostic features, immune features and drug sensitivity of the model were further evaluated. Single-cell data and microarray data were used to validate the differential expression of model genes between muscle-invasive and non-muscle-invasive BCa. The invasion and migration of BCa cells were evaluated using the transwell assay and wound-healing assay. The cell proliferation capacity was simultaneously evaluated using Colony formation experiments. The protein expression of the specific gene was detected by western blot analysis. Results: We identified 183 differentially expressed muscle-invasive-related differential genes (MIRDGs), among which four were selected to establish a prognostic model. Based on our signature, patients in different groups displayed varying levels of immune infiltration and immunotherapy profiles. Single-cell sequencing data and microarray data confirmed that four invasion-related genes were expressed at higher levels in muscle-invasive BCa. Given the critical role of S100A9 in the progression of BCa, we performed further analysis. The results showed that protein expression of S100A9 was high in muscle-invasive BCa, and S100A9 knockdown could inhibit the proliferation, migration and invasion of BCa. Conclusion: These findings demonstrated that the prognostic model for BCa patients was reasonably accurate and valid, and it may prove to be of considerable value for the treatment and prognosis of BCa patients in the future. S100A9 may become a better prognostic marker and potential therapeutic target to further guide clinical treatment decisions.

Disrupting Hedgehog signaling in melanocytes by SUFU knockout leads to ocular melanocytosis and anterior segment malformation.

Hedgehog (Hh) signaling is well known for its crucial role during development, but its specific role in individual cell lineages is less well characterized. Here, we disrupted Hh signaling specifically in melanocytes by using Cre-mediated cell-type-specific knockout of the Hh regulator suppressor of fused (Sufu). Interestingly, corresponding mice were fully pigmented and showed no developmental alterations in melanocyte numbers or distribution in skin and hair follicles. However, there were ectopic melanoblasts visible in the anterior chamber of the eye that eventually displayed severe malformation. Choroidal melanocytes remained unaltered. Surprisingly, the abnormal accumulation of anterior uveal melanoblasts was not the result of increased cell proliferation but of increased migration to ectopic locations such as the cornea. In melanoblasts in vitro, Sufu knockdown replicated the increase in cell migration without affecting proliferation and was mediated by an increased level of phosphorylated-ERK brought about by a reduction in the levels of the repressor form of GLI3. These results highlight the developmental divergence of distinct melanocyte subpopulations and may shed light on the pathogenesis of human ocular melanocytosis.

Aim2 Deficiency Ameliorates Lacrimal Gland Destruction and Corneal Epithelium Defects in an Experimental Dry Eye Model.

Purpose: Dry eye disease (DED) is a multifactorial disease that is associated with inflammation. Excessive DNA is present in the tear fluid of patients with DED. Absent in melanoma 2 (AIM2) is a key DNA sensor. This study aimed to investigate the role of AIM2 in the pathogenesis of DED. Methods: DED was induced by injection of scopolamine (SCOP). Aberrant DNA was detected by cell-free DNA (cfDNA) ELISA and immunostaining. Corneal epithelial defects were assessed by corneal fluorescein staining, zonula occludens-1 immunostaining and TUNEL. Tear production was analyzed by phenol red thread test. Lacrimal gland (LG) histology was evaluated by hematoxylin and eosin staining, and transmission electron microscopy examination. Macrophage infiltration in LG was detected by immunohistochemistry for the macrophage marker F4/80. Gene expression was analyzed by RT-qPCR. Protein production was examined by immunoblot analysis or ELISA. Results: Aim2-/- mice displayed a normal structure and function of LG and cornea under normal conditions. In SCOP-induced DED, wild type (WT) mice showed increased cfDNA in tear fluid, and aberrant accumulations of dsDNA accompanied by increased AIM2 expression in the LG. In SCOP-induced DED, WT mice displayed damaged structures of LG, reduced tear production, and severe corneal epithelium defects, whereas Aim2-/- mice had a better preserved LG structure, less decreased tear production, and improved clinical signs of dry eye. Furthermore, genetic deletion of Aim2 suppressed the increased infiltration of macrophages and inhibited N-GSDMD and IL18 production in the LG of SCOP-induced DED. Conclusions: Aim2 deficiency alleviates ocular surface damage and LG inflammation in SCOP-induced DED.

Clinical detection, diagnosis and treatment of morphological abnormalities of sperm flagella: A review of literature.

Sperm carries male genetic information, and flagella help move the sperm to reach oocytes. When the ultrastructure of the flagella is abnormal, the sperm is unable to reach the oocyte and achieve insemination. Multiple morphological abnormalities of sperm flagella (MMAF) is a relatively rare idiopathic condition that is mainly characterized by multiple defects in sperm flagella. In the last decade, with the development of high-throughput DNA sequencing approaches, many genes have been revealed to be related to MMAF. However, the differences in sperm phenotypes and reproductive outcomes in many cases are attributed to different pathogenic genes or different pathogenic mutations in the same gene. Here, we will review information about the various phenotypes resulting from different pathogenic genes, including sperm ultrastructure and encoding proteins with their location and functions as well as assisted reproductive technology (ART) outcomes. We will share our clinical detection and diagnosis experience to provide additional clinical views and broaden the understanding of this disease.

Patient with multiple morphological abnormalities of sperm flagella caused by a novel ARMC2 mutation has a favorable pregnancy outcome from intracytoplasmic sperm injection.

PURPOSE: To investigate the potential genetic cause in a primary infertility patient with multiple morphological abnormalities of sperm flagella (MMAF). METHODS: The patient's sperm was observed by light and electron microscopy. Whole-exome sequencing (WES) was carried out to identify candidate genes. Then, the mutation found by WES was verified by Sanger sequencing. The proteins interacting with ARMC2 were revealed by co-immunoprecipitation (co-IP) and mass spectrometry. Intracytoplasmic sperm injection (ICSI) was carried out to achieve successful pregnancy. RESULTS: Typical MMAF phenotype (absent, short, coiled, bent irregular flagella) was shown in the patient's sperm. A novel homozygous mutation in ARMC2 (c.1264C > T) was identified. The proteins interacting with ARMC2 we found were CEP78, PGAM5, RHOA, FXR1, and SKIV2L2. The ICSI therapy was successful, and boy-girl twins were given birth. CONCLUSION: We found a novel mutation in ARMC2 which led to MMAF and male infertility. This is the first report of ICSI outcome of patient harboring ARMC2 mutation. The interacting proteins indicated that ARMC2 might be involved in multiple processes of spermatogenesis.

Applications of Sponge Iron and Effects of Organic Carbon Source on Sulfate-Reducing Ammonium Oxidation Process.

The typical characteristics of wastewater produced from seafood, chemical, textile, and paper industries are that it contains ammonia, sulfate, and a certain amount of chemical oxygen demand (COD). The sulfate-reducing ammonium oxidation process is a biochemical reaction that allows both ammonia and sulfate removal, but its low growth rate and harsh reaction conditions limit its practical application. Due to the adsorption properties of the iron sponge and its robust structure, it provides a suitable living environment for microorganisms. To reduce the negative impact on the environment, we employed 4.8 kg of sponge iron in a 2.0 dm3 anaerobic sequencing batch reactor (ASBR). We investigated the effects of the type and concentration of carbon sources on the performance of the sulfate-reducing ammonium oxidation (SRAO) process. The results demonstrated that during a start-up period of 90 days, the average ammonium removal efficiency and the sulfate conversion efficiency of the reactor containing the sponge iron were 4.42% and 8.37% higher than those of the reactor without the sponge iron. The addition of the sponge iron shortens the start-up time of this greenhouse gas-free denitrification process and reduces future costs in practical applications. The removal of total nitrogen (TN) significantly increased after adding organic carbon sources and then declined sharply, while the most considerable reduction of ammonium removal efficiency from 98.4% to 30.5% was observed with adding phenol. The performance of the group employing glucose as the carbon source was recovered on the 28th day, with the average ammonium removal efficiency increasing from 49.03% to 83.5%. The results of this simulation study will help the rapid start-up of SRAO in the water treatment industry and can precisely guide the application of the SRAO process for wastewater containing different organic carbon sources.

Phosphorus removal from wastewater using electric arc furnace slag aggregate.

Electric arc furnace (EAF) slag aggregate, a waste by-product of the steel industry, exhibited a high potential for phosphorus (P) removal and had attracted considerable attention. The main objectives of this study were to evaluate the performance of using EAF slag aggregate as an adsorbent for P removal and identify its P removal capacity. A series of batch tests showed that P removal capacity of EAF slag increases gradually with the increase of pH with a range of 2-10, while the highest P removal capacity (1.94 mg/g) can be obtained at pH 12. The adsorption kinetics of P on EAF slag can be described by pseudo-second-order kinetic equations. Isothermal adsorption simulations showed that the best fitted model was the Freundlich model with a correlation coefficient of 0.9825. A continuous flow column experiment feeding a synthetic influent containing 15 mg P/L was operated for 60 days and the P removal efficiency was greater than 95% with a P removal capacity of 1.6 mg P/g slag. The results obtained in this study showed that EAF slag could act as an efficient adsorbent for P removal. Calcium phosphate precipitation depends on the release of Ca2+ and OH- by the dissolution of calcium oxide in EAF slag was found to be the dominant removal mechanism for P removal.

Molecular mechanisms of cancer cachexia­induced muscle atrophy (Review).

Muscle atrophy is a severe clinical problem involving the loss of muscle mass and strength that frequently accompanies the development of numerous types of cancer, including pancreatic, lung and gastric cancers. Cancer cachexia is a multifactorial syndrome characterized by a continuous decline in skeletal muscle mass that cannot be reversed by conventional nutritional therapy. The pathophysiological characteristic of cancer cachexia is a negative protein and energy balance caused by a combination of factors, including reduced food intake and metabolic abnormalities. Numerous necessary cellular processes are disrupted by the presence of abnormal metabolites, which mediate several intracellular signaling pathways and result in the net loss of cytoplasm and organelles in atrophic skeletal muscle during various states of cancer cachexia. Currently, the clinical morbidity and mortality rates of patients with cancer cachexia are high. Once a patient enters the cachexia phase, the consequences are difficult to reverse and the treatment methods for cancer cachexia are very limited. The present review aimed to summarize the recent discoveries regarding the pathogenesis of cancer cachexia­induced muscle atrophy and provided novel ideas for the comprehensive treatment to improve the prognosis of affected patients.

The integrative analysis of DNA methylation and mRNA expression profiles confirmed the role of selenocompound metabolism pathway in Kashin-Beck disease.

Kashin-Beck disease (KBD) is an endemic chronic osteochondropathy. The etiology of KBD remains unknown. In this study, we conducted an integrative analysis of genome-wide DNA methylation and mRNA expression profiles between KBD and normal controls to identify novel candidate genes and pathways for KBD. Articular cartilage samples from 17 grade III KBD patients and 17 healthy controls were used in this study. DNA methylation profiling of knee cartilage and mRNA expression profile data were obtained from our previous studies. InCroMAP was performed to integrative analysis of genome-wide DNA methylation profiles and mRNA expression profiles. Gene ontology (GO) enrichment analysis was conducted by online DAVID 6.7. The quantitative real-time polymerase chain reaction (qPCR), Western blot, immunohistochemistry (IHC), and lentiviral vector transfection were used to validate one of the identified pathways. We identified 298 common genes (such as COL4A1, HOXA13, TNFAIP6 and TGFBI), 36 GO terms (including collagen function, skeletal system development, growth factor), and 32 KEGG pathways associated with KBD (including Selenocompound metabolism pathway, PI3K-Akt signaling pathway, and TGF-beta signaling pathway). Our results suggest the dysfunction of many genes and pathways implicated in the pathogenesis of KBD, most importantly, both the integrative analysis and in vitro study in KBD cartilage highlighted the importance of selenocompound metabolism pathway in the pathogenesis of KBD for the first time.

The Importance of Se-Related Genes in the Chondrocyte of Kashin-Beck Disease Revealed by Whole Genomic Microarray and Network Analysis.

Kashin-Beck disease (KBD) is an endemic, chronic, and degenerative osteoarthropathy. Selenium (Se) deficiency plays important role in the pathogenesis of KBD. We aimed to screen Se-related gene from chondrocytes of patients with KBD. Whole-genome oligonucleotide microarrays were used to detect differentially expressed genes. qRT-PCR was used to confirm the microarray results. Comparative Toxicogenomics Database (CTD) was used to screen Se-related genes from differentially expressed genes. Gene Ontology (GO) classifications and network analysis of Se-related genes were constituted by STRING online system. Three hundred ninety-nine differentially expressed genes were obtained from microarray. Among them, 54 Se-related genes were identified by CTD. The qRT-PCR validation showed that four genes expressed similarly with the ones in the microarray transcriptional profiles. The Se-related genes were categorized into 6 cellular components, 8 molecular functions, 44 biological processes, 10 pathways, and 1 network by STRING. The Se-related gene insulin-like growth factor binding protein 2 (IGFBP2), insulin-like growth factor binding protein 3 (IGFBP3), interleukin 6 (IL6), BCL2, apoptosis regulator (BCL2), and BCL2-associated X, apoptosis regulator (BAX), which involved in many molecular functions, biological processes, and apoptosis pathway may play important roles in the pathogenesis of KBD.

Hydrophobic drug adsorption loss to syringe filters from a perspective of drug delivery.

Filtering with a syringe filter is a common operation in pharmaceutical analysis. Ophthalmic research often has a limited amount of sample and low amount of drug which is vulnerable to filtering membrane adsorption loss but not well recognized in the research community. Current study investigated drug adsorption by 11 types of syringe filters for 4 hydrophobic compounds commonly encountered in transscleral drug delivery. Among the 11 types of syringe filters surveyed, polytetrafluoroethylene - NBA, polytetrafluoroethylene - NLA, and polypropylene filters caused the least adsorptive drug loss for these four drugs studied. The magnitude of drug adsorption was filter- and drug-specific. Polytetrafluoroethylene-NLA caused the least adsorptive loss (1%) for triamcinolone acetonide, polytetrafluoroethylene-NBA caused the least adsorptive loss (5.4%) for diclofenac, and polypropylene caused the least adsorptive loss for cyclosporine A, 16.8% on average. Tacrolimus had the least adsorptive loss to the filters of polytetrafluoroethylene - NLA and polypropylene; however, the percentage of adsorptive loss from filtration was the highest (32% loss in average) among the four drugs surveyed. CONCLUSION: Low drug concentrations as seen in samples from ophthalmic researches are vulnerable to filtration drug loss. Selecting the right filter via validation is critical to avoid underestimating the drug level and distorting the resultant distribution/clearance profile in the ocular pharmacokinetic analysis.

Cryptotanshinone inhibits RANKL-induced osteoclastogenesis by regulating ERK and NF-κB signaling pathways.

Osteoporosis (OS) is one of the most common healthy problems characterized by low bone mass. Osteoclast, the primary bone-resorbing cell, is responsible for destructive bone diseases including osteoporosis (OS). Cryptotanshinone (CTS), an active component extracted from the root of Salvia miltiorrhiza bunge, has been shown to prevent the destruction of cartilage and the thickening of subchondral bone in mice osteoarthritis models. However, its molecular mechanism in osteoclastogenesis needs to be determined. The aim of the current study was to explore the effect of CTS on osteoclastogenesis and further evaluate the underlying mechanism. Our results showed that CTS inhibited receptor activator of NF-κB ligand (RANKL)-induced the increase in tartrate-resistant acid phosphatase (TRAP) activity in bone marrow-derived macrophages (BMMs). In addition, the expressions of osteoclastogenesis-related marker proteins and nuclear factor of activated T-cells (NFAT) activation were suppressed by CTS treatment in BMMs. Furthermore, CTS attenuated RANKL-induced ERK phosphorylation and NF-κB activation in BMMs. These findings indicated that CTS inhibited RANKL-induced osteoclastogenesis by inhibiting ERK phosphorylation and NF-κB activation in BMMs. Thus, CTS may function as an inhibitor of osteoclastogenesis and may be considered as an alternative medicine for the prevention and treatment of OS.

The osteoarthritis-associated gene PAPSS2 promotes differentiation and matrix formation in ATDC5 chondrogenic cells.

3'-Phosphoadenosine 5'-phosphosulfate synthetase 2 (PAPSS2) has been shown to be important in the development of normal skeletal structure. The aim of the present study was to evaluate the role of PAPSS2 in the differentiation of chondrocytes as well as their mechanisms. Using RNA interference-mediated via a lentivirus and a retrovirus, PAPSS2 gene silence and overexpression in ATDC5 chondrogenic cells were performed. Chondrocyte differentiation and chondrogenic-related gene markers associated with extracellular matrix formation were noted. The mRNA and protein expression for Wnt4, ß-catenin and SOX9 genes were observed. The PAPSS2 transcript expression levels progressively decline in ATDC5-induced chondrocyte-like cells during differentiation. Silencing of PAPSS2 expression had a significantly attenuating effect on cell differentiation and decreased expression of collagen II and X. In contrast, over-expression of PAPSS2 promoted the differentiation of ATDC5 chondrogenic cells. The mRNA expression levels of Wnt4 and SOX9 decreased significantly in PAPSS2 knock down cells vs. control cells. However, this expression was increased in the cells over-expressing PAPSS2. These data indicate that PAPSS2 regulates aggrecan activity as well as cell differentiation. The findings favor a mechanism by which PAPSS2 induces differentiation in ATDC5 cells via direct regulation of early signaling events that promote formation of collagenous matrix components. This control is probably mediated via extracellular matrix formation Wnt/ß-catenin signaling pathways.

Down-regulation of miR-193a-3p promotes osteoblast differentiation through up-regulation of LGR4/ATF4 signaling.

Emerging evidence indicates that microRNAs (miRNAs) are crucial regulators of osteoblast differentiation. A previous study has reported that miR-193a-3p expression is altered during the induction of osteoblast differentiation. However, the precise biological function and regulatory mechanism of miR-193a-3p during osteoblast differentiation remains unclear. In this study, we aimed to investigate the precise role and underlying mechanism of miR-193a-3p in regulating osteoblast differentiation. The results showed that miR-193a-3p expression was significantly down-regulated during the induction of osteoblast differentiation. Functional experiments demonstrated that the overexpression of miR-193a-3p impeded osteoblast differentiation while miR-193a-3p inhibition promoted osteoblast differentiation. Bioinformatics analysis and a luciferase assay revealed that leucine-rich repeat-containing G-protein coupled receptor 4 (LGR4), a critical regulator of osteoblast differentiation, was a target gene of miR-193a-3p. We showed that miR-193a-3p negatively regulated the expression of LGR4 and activating transcription factor 4 (ATF4). Moreover, the knockdown of LGR4 or ATF4 significantly reversed the promotion effect of miR-193a-3p inhibition on osteoblast differentiation. Overall, these findings demonstrate that miR-193a-3p regulates osteoblast differentiation by modulating LGR4/ATF4 signaling and suggests that the miR-193a-3p/LGR4/ATF4 regulation axis may play an important role in regulating bone remodeling.

The efficacy and safety of intra-articular injection of hyaluronic acid in the knee and physical therapy agents to treat Kashin-Beck disease: A prospective interventional study.

The aim of the present study was to determine whether hyaluronic acid (HA) or physical therapy agents (PTA) can improve functional parameters in patients with knee Kashin-Beck disease (KBD). For 2 years, patients (n=55) were treated with HA weekly for 5 weeks, then received 6th and 7th injections on the 3rd and 6th month, respectively, for 7 injections in total. Patients (n=53) were treated with PTA five times a week for 3 weeks every month for 6 months. The patients were evaluated with the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) and the visual analog pain scale (VAS). Trial registration, ChiCTR-TRC-12002189 (http://www.chictr.org/). During the study, following treatment interruption, pain increased in the PTA group (from a mean value of 85.7±83.8 mm at month 12 to 145.2±128.8 mm at month 18 and 201.3±150.5 mm at month 24), while it remained stable in the HA group (from a mean value of 80.7±70.6 mm at month 12 to 90.1±95.2 mm at month 18 and 82.6±85.3 mm at month 24), with a statistically significant difference in favor of HA at month 18 (P<0.05) and month 24 (P<0.05). Joint stiffness, physical function and total WOMAC showed the same trend as pain. The global efficacy judgments by the patients and the investigators showed a statistically significant difference in favor of HA at month 18 (P<0.05) and month 24 (P<0.05). In conclusion, although all the patients improved in terms of pain and function, HA was superior to PTA alone for pain relief and lasting effect.

To screen the effective software for analysing gene interactions from Kashin-Beck disease genome profiling pathway and network, according to the tool of GeneMANIA.

In order to screen the more effective software for the pathway and network analysis of Kashin-Beck disease, gene microarrays, TranscriptomeBrowser, MetaCore and GeneMANIA were used for analysis. Three significant chondrocytic pathways and one network were screened by TranscriptomeBrowser; one significant pathway and one network were identified by MetaCore. BAX, APAF1, CASP6, BCL2, VEGF, SOCS3, BAK, TGFBI, TNFAIP6, TNFRSF11B and THBS1 were significant genes associated with the biological function of chondrocyte or cartilage involved in the TranscriptomeBrowser or MetaCore results. The interactions between the significant genes and their adjacent genes were searched and classified in GeneMANIA. In pathway analysis results, TranscriptomeBrowser is superior to get the interaction of pathway and co-expression compared with MetaCore; MetaCore is superior to get the interaction of physical interaction compared with TranscriptomeBrowser. In network analysis results, TranscriptomeBrowser contains more interaction message of co-localisation, MetaCore contains, more interaction message of co-expression.

Role of inflammation in the process of clinical Kashin-Beck disease: latest findings and interpretations.

Kashin-Beck disease (KBD), a particular type of osteoarthritis (OA), and an endemic disease with articular cartilage damage and chondrocytes apoptosis, can affect many joints, and the most commonly affected joints are the knee, ankle, and hand. KBD has traditionally been classified as a non-inflammatory OA. However, recent studies have shown that inflammation has played an important role in the development of KBD. Nowadays, clinical KBD is not only an endemic disease, but also a combined result of many other non-endemic factors, which contains age, altered biomechanics, joint trauma and secondary OA. The characteristics of the developmental joint failure of advanced KBD, because of the biochemical and mechanical processes, are tightly linked with the interaction of joint damage and its immune response, as well as the subsequent state of chronic inflammation leading to KBD progression. In this review, we focus on the epidemiology, pathology, imaging, cytokines and transduction pathways investigating the association of inflammation with KBD; meanwhile, a wide range of data will be discussed to elicit our current hypotheses considering the role of inflammation and immune activation in KBD development.

Panax notoginseng stimulates alkaline phosphatase activity, collagen synthesis, and mineralization in osteoblastic MC3T3-E1 cells.

Total Panax notoginseng saponin (PNS) has been extensively used to treat a variety of diseases, such as bone fractures, soft tissue injuries, etc. In this study, mouse calvaria-original osteoblastic MC3T3-E1 cells were cultured in various concentrations of PNS (0.005-5 mg/mL) during the period (1, 5, 14, and 23 d). At the endpoint, the osteogenic capacity of MC3T3-E1 cells was investigated by measuring the alkaline phosphatase (ALP) activity, the deposited calcium, and the expression of osteogenic-related markers, including bone collagen type 1 (Col1) and osteocalcin (OCN). Compared with all groups in each period, the most pronounced effect was observed at the concentration range between 0.05 and 0.5 mg/mL (P < 0.05) and the cell proliferation with PNS treatment was found during the whole osteogenic period. Moreover, cellular ALP activity with PNS was increased during 7, 14, and 21 d and cell mineralization with PNS was enhanced in 14 and 21 d. Furthermore, the differentiation markers Col1 and OCN increased in the PNS-treated cells. Our work suggests that PNS may stimulate the osteogenesis process which contains osteoblastic proliferation, differentiation, and mineralization by increasing cellular ALP activity, extracellular matrix mineralization, and osteoblast-associated molecules in the osteoblasts.

Effect of bone mesenchymal stem cells transplantation on the micro-environment of early osteonecrosis of the femoral head.

Autologous implantation of bone mesenchymal stem cells (BMSCs) has achieved promising clinical efficacy for the treatment of early-stage osteonecrosis of the femoral head (ONFH). However, the underlying mechanisms are not completely elucidated. Here, we investigated the effect of BMSCs on the early ONFH in vitro and in vivo. In co-cultured system, primary BMSCs enhanced the activity and inhibited the apoptosis of primary OB. The concentrations of VEGF and BMP-2 in the co-cultured medium were significantly higher than those without co-culture. Importantly, BMSCs implantation increased OB, capillaries and VEGF and BMP-2 expressions of the necrotic areas of femoral head in the ONFH rabbits. In conclusion, our results indicated that BMSCs treated the early ONFH possibly through increasing OB and capillaries, as well as VEGF and BMP-2 expression in the femoral head. These results provided possible mechanisms for the treatment of early-stage ONFH with BMSCs transplantation.