[Tumor-induced osteomalacia caused by an orbital tumor: a case report].

A 52-year-old patient was initially diagnosed as hypophosphatemic osteomalacia in the Department of Endocrinology due to knee, foot and lumbosacral pain. The symptoms were not significantly relieved after phosphorus and vitamin D supplementation. Later, the imaging examination showed an orbital tumor in the right eye. The tumor was surgically removed, and the symptoms of systemic bone pain were relieved.

Magnetic nanofluid behavior including an immersed rotating conductive cylinder: finite element analysis.

In this paper, numerical Galerkin Finite Element Method (GFEM) is applied for conjugate heat-transfer of a rotating cylinder immersed in Fe3O4-water nanofluid under the heat-flux and magnetic field. The outer boundaries of the cavity were maintained at low temperatures while beside the cylinder were insulated. It is assumed that the cylinder rotates in both clockwise and counter-clockwise directions. The dimensionless governing equations such as velocity, pressure, and temperature formulation were analyzed by the GFEM. The results were evaluated using the governing parameters such as nanoparticles (NPs) volume fraction, Hartmann and Rayleigh numbers, magnetic field angle and NPs shapes. As a main result, the average Nusselt number increases by increasing the NPs volume fraction, inclination angle and thermal conductivity ratios, while increasing the Hartmann number decreased the Nusselt number. Furthermore, platelet NPs had the maximum average Nusselt number and spherical NPs made the minimum values of Nusselt numbers among examined NPs shapes.

Axin2+-Mesenchymal PDL Cells, Instead of K14+ Epithelial Cells, Play a Key Role in Rapid Cementum Growth.

To date, attempts to regenerate functional periodontal tissues (including cementum) are largely unsuccessful due to a lack of full understanding about the cellular origin (epithelial or mesenchymal cells) essential for root cementum growth. To address this issue, we first identified a rapid cementum growth window from the ages of postnatal day 28 (P28) to P56. Next, we showed that expression patterns of Axin2 and ß-catenin within cementum-forming periodontal ligament (PDL) cells are negatively associated with rapid cementum growth. Furthermore, cell lineage tracing studies revealed that the Axin2+-mesenchymal PDL cells and their progeny rapidly expand and directly contribute to postnatal acellular and cellular cementum growth. In contrast, the number of K14+ epithelial cells, which were initially active at early stages of development, was reduced during rapid cementum formation from P28 to P56. The in vivo cell ablation of these Axin2+ cells using Axin2CreERT2/+; R26RDTA/+ mice led to severe cementum hypoplasia, whereas constitutive activation of ß-catenin in the Axin2+ cells resulted in an acceleration in cellular cementogenesis plus a transition from acellular cementum to cellular cementum. Thus, we conclude that Axin2+-mesenchymal PDL cells, instead of K14+ epithelial cells, significantly contribute to rapid cementum growth.

Tissue Clearing and Its Application to Bone and Dental Tissues.

Opaqueness of animal tissue can be attributed mostly to light absorption and light scattering. In most noncleared tissue samples, confocal images can be acquired at no more than a 100-µm depth. Tissue-clearing techniques have emerged in recent years in the neuroscience field. Many tissue-clearing methods have been developed, and they all follow similar working principles. During the tissue-clearing process, chemical or physical treatments are applied to remove components blocking or scattering the light. Finally, samples are immersed in a designated clearing medium to achieve a uniform refractive index and to gain transparency. Once the transparency is reached, images can be acquired even at several millimeters of depth with high resolution. Tissue clearing has become an essential tool for neuroscientists to investigate the neural connectome or to analyze spatial information of various types of brain cells. Other than neural science research, tissue-clearing techniques also have applications for bone research. Several methods have been developed for clearing bones. Clearing treatment enables 3-dimensional imaging of bones without sectioning and provides important new insights that are difficult or impossible to acquire with conventional approaches. Application of tissue-clearing technique on dental research remains limited. This review will provide an overview of the recent literature related to the methods and application of various tissue-clearing methods. The following aspects will be covered: general principles for the tissue-clearing technique, current available methods for clearing bones and teeth, general principles of 3-dimensional imaging acquisition and data processing, applications of tissue clearing on studying biological processes within bones and teeth, and future directions for 3-dimensional imaging.

Pulsed electromagnetic fields preserve bone architecture and mechanical properties and stimulate porous implant osseointegration by promoting bone anabolism in type 1 diabetic rabbits.

The effects of exogenous pulsed electromagnetic field (PEMF) stimulation on T1DM-associated osteopathy were investigated in alloxan-treated rabbits. We found that PEMF improved bone architecture, mechanical properties, and porous titanium (pTi) osseointegration by promoting bone anabolism through a canonical Wnt/ß-catenin signaling-associated mechanism, and revealed the clinical potential of PEMF stimulation for the treatment of T1DM-associated bone complications. INTRODUCTION: Type 1 diabetes mellitus (T1DM) is associated with deteriorated bone architecture and impaired osseous healing potential; nonetheless, effective methods for resisting T1DM-associated osteopenia/osteoporosis and promoting bone defect/fracture healing are still lacking. PEMF, as a safe and noninvasive method, have proven to be effective for promoting osteogenesis, whereas the potential effects of PEMF on T1DM osteopathy remain poorly understood. METHODS: We herein investigated the effects of PEMF stimulation on bone architecture, mechanical properties, bone turnover, and its potential molecular mechanisms in alloxan-treated diabetic rabbits. We also developed novel nontoxic Ti2448 pTi implants with closer elastic modulus with natural bone and investigated the impacts of PEMF on pTi osseointegration for T1DM bone-defect repair. RESULTS: The deteriorations of cancellous and cortical bone architecture and tissue-level mechanical strength were attenuated by 8-week PEMF stimulation. PEMF also promoted osseointegration and stimulated more adequate bone ingrowths into the pore spaces of pTi in T1DM long-bone defects. Moreover, T1DM-associated reduction of bone formation was significantly attenuated by PEMF, whereas PEMF exerted no impacts on bone resorption. We also found PEMF-induced activation of osteoblastogenesis-related Wnt/ß-catenin signaling in T1DM skeletons, but PEMF did not alter osteoclastogenesis-associated RANKL/RANK signaling gene expression. CONCLUSION: We reveal that PEMF improved bone architecture, mechanical properties, and pTi osseointegration by promoting bone anabolism through a canonical Wnt/ß-catenin signaling-associated mechanism. This study enriches our basic knowledge for understanding skeletal sensitivity in response to external electromagnetic signals, and also opens new treatment alternatives for T1DM-associated osteopenia/osteoporosis and osseous defects in an easy and highly efficient manner.

Osteochondral Interface Stiffening in Mandibular Condylar Osteoarthritis.

Osteoarthritis (OA) of the temporomandibular joint (TMJ) is associated with dental biomechanics. A major change during OA progression is the ossification of the osteochondral interface. This study investigated the formation, radiological detectability, and mechanical property of the osteochondral interface at an early stage, the pathogenesis significance of which in OA progression is of clinical interest and remains elusive for the TMJ. Unilateral anterior crossbite (UAC) was performed on 6-wk-old rats as we previously reported. TMJs were harvested at 4, 12, and 20 wk. The progression of TMJ OA was evaluated using a modified Osteoarthritis Research Society International (OARSI) score system. Osteochondral interface was investigated by quantifying the thickness via von Kossa staining of histological slices and in vivo calcium deposition by calcein injection. Tissue ossification was imaged by micro-computed tomography (CT). Mechanical properties were measured at nanoscale using dynamic indentation. Time-dependent TMJ cartilage lesions were elicited by UAC treatment. Geometric change of the condyle head and increased value of the OARSI score were evident in UAC TMJs. At the osteochondral interface, there was not only enhanced deep-zone cartilage calcification but also calcium deposition at the osseous boundary. The thickness, density, and stiffness of the osteochondral interface were all significantly increased. The enhanced ossification of the osteochondral interface is a joint outcome of the aberrant deeper cartilage calcification at the superior region and promoted formation of subchondral cortical bone at the inferior region. The micro-CT detectable ossification from an early stage thus is of diagnostic significance. Although the environment of the cartilage and subchondral bone could be changed due to the stiffness of the interface, whether or not the stiffened interface would accelerate OA progress remains to be confirmed. With that evidence, the osteochondral interface could be a new diagnostic and therapeutic target of the mechanically initiated OA in the TMJ.

Novel stent in the palliation of malignant esophageal strictures: a retrospective study.

The placement of metal stents is often used as a palliative treatment for malignant esophageal stenosis. We designed a novel stent that has been used clinically since 2011, and we therefore performed a retrospective study to compare the therapeutic effects of this novel metal stent to a conventional partially covered metal stent in patients with malignant esophageal strictures. The records of 201 consecutive patients who underwent placement of either the conventional partially covered metal stents (Group A, n = 92) or the new metal stents (Group B, n = 109) in the Endoscopy Center of General Hospital of Chengdu Military Command from October 2008 to March 2013 were reviewed. The median dysphagia score significantly improved in both groups 1 week following stent placement (P < 0.001). No significant differences were observed in success rate (P = 0.910) or the complication rate (P = 0.426) between groups. Six months after stent placement, recurrent dysphagia due to stent migration, tissue ingrowth or overgrowth or food obstruction occurred in 45% and 29% of patients in the conventional stent and new stent groups, respectively. The results of this retrospective study indicate that the new modified self-expandable metal stents (SEMS) is at least as safe and effective as the conventional partially covered SEMS in treatment of malignant esophageal strictures.

Anti-tumor role of Bacillus subtilis fmbJ-derived fengycin on human colon cancer HT29 cell line.

To explore the potential clinical anti-tumor roles of Bacillus subtilis fmbJ-derived fengycin on cell growth and apoptosis in colon cancer HT29 cell line.Fengycin was extracted from Bacillus subtilis fmbJ and detected using HPLC. The effects of different concentration of fengycin on colon cell HT29 cell activity at different time points were analyzed using MTT assay. ROS level in colon HT29 cells affected by fengycin was detected using DCFH-DA method, followed by measuring the effects of fengycin on HT29 cell apoptosis and cell cycle by flow cytometry. The effects of fengycin on Bax/Bcl-2, CDK4/cyclin D1, Caspase-6 and Caspase-3 expressions in HT29 cells were analyzed using western blot. Also, mRNA levels of Bax/Bcl-2 and CDK4/cyclin D1 in HT29 cells affected by fengycin were analyzed using qRT-PCR.Compared with controlss, 20 µg/mL of fengycin performed an inhibit role on HT29 cell growth of at 3 day (P<0.05), and high dose of fengycin showed more excellent effect on inhibiting HT29 cell growth with time increasing. Besides, fengycin could induce HT29 cell apoptosis and affect the cell cycle arrest at G1. ROS level in HT29 cells treated by fengycin was significantly increased compared with that in control group (P<0.05). Western blot analysis showed that after being treated with fengycin, Bax, Caspase-3, and Caspase-6 expressions were increased, however, Bcl-2, and CDK4/cyclin D1 expressions were decreased (P<0.05).Our study suggested that fengycin may play certain inhibit roles in the development and progression of colon cancer through involving in the cell apoptosis and cell cycle processes by targeting the Bax/Bcl-2 pathway.

The preventive effects of pulsed electromagnetic fields on diabetic bone loss in streptozotocin-treated rats.

UNLABELLED: The present study was the first report demonstrating that pulsed electromagnetic field (PEMF) could partially prevent bone strength and architecture deterioration and improve the impaired bone formation in streptozotocin-induced diabetic rats. The findings indicated that PEMF might become a potential additive method for inhibiting diabetic osteopenia or osteoporosis. INTRODUCTION: Diabetes mellitus (DM) can cause various musculoskeletal abnormalities. Optimal therapeutic methods for diabetic bone complication are still lacking. It is essential to develop more effective and safe therapeutic methods for diabetic bone disorders. Pulsed electromagnetic field (PEMF) as an alternative noninvasive method has proven to be effective for treating fracture healing and osteoporosis in non-diabetic conditions. However, the issue about the therapeutic effects of PEMF on diabetic bone complication has not been previously investigated. METHODS: We herein systematically evaluated the preventive effects of PEMF on diabetic bone loss in streptozotocin-treated rats. Two similar experiments were conducted. In each experiment, 16 diabetic and eight non-diabetic rats were equally assigned to the control, DM, and DM + PEMF group. DM + PEMF group was subjected to daily 8-h PEMF exposure for 8 weeks. RESULTS: In experiment 1, three-point bending test suggested that PEMF improved the biomechanical quality of diabetic bone tissues, evidenced by increased maximum load, stiffness, and energy absorption. Microcomputed tomography analysis demonstrated that DM-induced bone architecture deterioration was partially reversed by PEMF, evidenced by increased Tb.N, Tb.Th, BV/TV, and Conn.D and reduced Tb.Sp and SMI. Serum OC analysis indicated that PEMF partially prevented DM-induced decrease in bone formation. In experiment 2, no significant difference in the bone resorption marker TRACP5b was observed. These biochemical findings were further supported by the dynamic bone histomorphometric parameters BFR/BS and Oc.N/BS. CONCLUSIONS: The results demonstrated that PEMF could partially prevent DM-induced bone strength and architecture deterioration and improve the impaired bone formation. PEMF might become a potential additive method for inhibiting diabetic osteoporosis.

Effect of brain-derived neurotrophic factor haploinsufficiency on stress-induced remodeling of hippocampal neurons.

Chronic restraint stress (CRS) induces the remodeling (i.e., retraction and simplification) of the apical dendrites of hippocampal CA3 pyramidal neurons in rats, suggesting that intrahippocampal connectivity can be affected by a prolonged stressful challenge. Since the structural maintenance of neuronal dendritic arborizations and synaptic connectivity requires neurotrophic support, we investigated the potential role of brain derived neurotrophic factor (BDNF), a neurotrophin enriched in the hippocampus and released from neurons in an activity-dependent manner, as a mediator of the stress-induced dendritic remodeling. The analysis of Golgi-impregnated hippocampal sections revealed that wild type (WT) C57BL/6 male mice showed a similar CA3 apical dendritic remodeling in response to three weeks of CRS to that previously described for rats. Haploinsufficient BDNF mice (BDNF(±) ) did not show such remodeling, but, even without CRS, they presented shorter and simplified CA3 apical dendritic arbors, like those observed in stressed WT mice. Furthermore, unstressed BDNF(±) mice showed a significant decrease in total hippocampal volume. The dendritic arborization of CA1 pyramidal neurons was not affected by CRS or genotype. However, only in WT mice, CRS induced changes in the density of dendritic spine shape subtypes in both CA1 and CA3 apical dendrites. These results suggest a complex role of BDNF in maintaining the dendritic and spine morphology of hippocampal neurons and the associated volume of the hippocampal formation. The inability of CRS to modify the dendritic structure of CA3 pyramidal neurons in BDNF(±) mice suggests an indirect, perhaps permissive, role of BDNF in mediating hippocampal dendritic remodeling.

Drosophila lacks C20 and C22 PUFAs.

Drosophila melanogaster has been considered a model organism for investigating human diseases and genetic pathways. Whether Drosophila is an ideal model for nutrigenomics, especially for FA metabolism, however, remains to be illustrated. The aim of this study was to examine the metabolism of C20 and C22 PUFAs in Drosophila. Analysis of FA composition revealed a complete lack of C20 and C22 PUFAs in the body tissue of larvae, pupae, and adult flies fed either a base or supplemented diet abundant in the PUFA precursors linoleic acid and α-linolenic acid. PUFA with >C20 could only be found in flies supplemented with specific FAs. Interestingly, the supplemented C22 PUFAs docosahexaenoic acid (22:6n-3) and docosatetraenoic acid (22:4n-6) were largely converted to the shorter chain C20 PUFAs eicosapentaenoic acid (20:5n-3) and arachidonic acid (20:4n-6), respectively. Furthermore, a genome sequence scan indicated that no gene encoding Δ-6/ Δ-5 desaturases, the key enzymes for the synthesis of C20/C22 PUFA, was present in Drosophila. These findings demonstrate that Drosophila lacks the capability to synthesize the biologically important C20 and C22 PUFAs, and thereby argue that Drosophila is not a valid model for the study of lipid metabolism and related diseases.

CD49d blockade by natalizumab in patients with multiple sclerosis affects steady-state hematopoiesis and mobilizes progenitors with a distinct phenotype and function.

Therapeutic application of natalizumab, an anti-CD49d Ab, in patients with multiple sclerosis (MS) has been associated with increased levels of circulating CD34+ progenitors. We analyzed the frequency, phenotype and functional activity of CD34+ HSC in blood and BM of patients with MS who were treated with natalizumab. Compared with healthy controls and untreated MS patients, natalizumab treatment increased CD34+ cells in the peripheral blood 7-fold and in BM 10-fold. CD34+ cells derived from blood and marrow of natalizumab-treated patients expressed less of the stem cell marker CD133, were enriched for erythroid progenitors (CFU-E) and expressed lower levels of adhesion molecules than G-CSF-mobilized CD34+ cells. The level of surface CXCR-4 expression on CD34+ cells from patients treated with natalizumab was higher compared with that of CD34+ cells mobilized by G-CSF (median 43.9 vs 15.1%). This was associated with a more than doubled migration capacity toward a chemokine stimulus. Furthermore, CD34+ cells mobilized by natalizumab contained more mRNA for p21 and less for matrix metallopeptidase 9 compared with G-CSF-mobilized hematopoietic stem cell (HSC). Our data indicate that G-CSF and CD49d blockade mobilize different HSC subsets and suggest that both strategies may be differentially applied in specific cell therapy approaches.

Effects of soybean oil and linseed oil on fatty acid compositions of muscle lipids and cooked pork flavour.

This study was conducted to investigate the effects of dietary oil on the fatty acid compositions of the longissimus and biceps brachii muscles and its effects on cooked muscles flavour. Seventy-two crossbred barrows (Duroc×Landrace×Large White), were blocked by weight and randomly assigned to one of three treatments. The three dietary treatments were: (a) no oil supplement (CON); (b) 3% soybean oil supplement (SO3); (c) 3% linseed oil supplement (LO3). Dietary linseed oil and soybean oil significantly increased the contents of C18:3 and C18:2 in the neutral lipids and phospholipids in both longissimus muscle and biceps brachii muscle, respectively. Aroma compounds analysis indicated only few aroma compounds were affected significantly by dietary oil in both cooked longissimus muscle and biceps brachii muscle. The flavour attributes of cooked longissimus muscle and biceps brachii muscle were not influenced by feeding 3% soybean oil. Feeding 3% linseed oil did not deleteriously affect the flavour of cooked longissimus muscle but cooked biceps brachii muscle from LO3 had significantly lower pork flavour and higher abnormal flavour than CON and SO3.

Inhibition of platelet-derived growth factor receptorbeta by imatinib mesylate suppresses proliferation and alters differentiation of human mesenchymal stem cells in vitro.

OBJECTIVES: Recent data show that Imatinib mesylate (IM) also affects haematopoietic stem cells (HSC), T lymphocytes and dendritic cells that do not harbour constitutively active tyrosine kinases. MATERIALS AND METHODS: We evaluated possible effects of IM on human bone marrow-derived mesenchymal stem cells (MSC) in vitro. RESULTS: Screening the activity of 42 receptor tyrosine kinases revealed an exclusive inhibition of platelet-derived growth factor receptorbeta (PDGFRbeta). Analysis of downstream targets of PDGFRbeta demonstrated IM-mediated reduction of Akt and Erk1/2 phosphorylation. Culture of MSC with IM led to the reversible development of perinuclear multi-vesicular bodies. The proliferation and clonogenicity of MSC were significantly reduced compared to control cultures. IM favoured adipogenic differentiation of MSC whereas osteogenesis was suppressed. The functional deficits described led to a 50% reduction in the support of clonogenic haematopoietic stem cells, cultured for 1 month on a monolayer of MSC with IM. CONCLUSION: In summary, inhibition of PDGFRbeta and downstream Akt and Erk signalling by IM has a significant impact on proliferation and differentiation of human MSC in vitro.

The role of Kupffer cells in non-alcoholic steatohepatitis of rats chronically fed with high-fat diet.

OBJECTIVE: To explore the role of Kupffer cells in non-alcoholic steatohepatitis (NASH) by means of rat model. METHODS: Nineteen male SD rats were randomized into model group (n=10) and normal group (n=9), with a high-fat diet and standard diet for 12 weeks, respectively. Routine histologic features of hepatic section were observed by HE staining. The number and shape of Kupffer cells in the liver were detected by immunohistochemistry and penetrated electron microscope, respectively. RESULTS: All rats of model group developed NASH, which was characterized by obesity and hyperlipidemia. Histopathological examination showed hepatocellular macrovesicular steatosis, lobular inflammatory cell infiltration and necrosis. Compared with normal group, the count of Kupffer cells in the liver was largely increased, and the Kupffer cells in the model group were activated to some extent. Furthermore, these changes of Kupffer cells were in accordance with the degree of steatosis, inflammation and necrosis in the liver of the model group. CONCLUSION: The number and activity of Kupffer cells are increased significantly in NASH induced by high-fat diet, and Kupffer cells might be involved in the pathogenesis of steatohepatitis.

Crystallization and preliminary X-ray analysis of a bacteriophage T4 primase fragment.

The primase from bacteriophage T4 is a single-stranded DNA-dependent RNA polymerase that is one of the seven proteins that constitute the DNA-replication machinery of bacteriophage T4. In an attempt to crystallize the protein, a number of variants were generated. One such construct, which includes the C-terminal region (residues 196-340), gave four different crystal forms which diffract in the 3. 5-6.0 A resolution range.

[The disposing techniques of evoked potentials].

This paper is to bring forward the new disposing techniques of evoked potentials which include four aspect techniques of the averaging, the recording, digital sampling and filters about the averaging, evoked potential amplitude, evoked potential latency, evoked potential recording, and evoked potential generations. The technique of the averaging including signal filtering and a periodic averaging, can enhance EP dedection. The commercial EP machines also plot changes in latency between serial EP studies in order to detect trends in peak latency. The modern digital EP recording device consists of sensory stimator, recording amplifiers with analog filters, an analog-to-digital converter, a digital signal averager, and a display and storage system. A sample-and-hold function is one of the recent developments which used EP collectors that provide simultaneous recording with multiple channels employing different time and voltage scales and sampling rates. The EP data may be further processed following A-D conversion by digital filters.

Interactions of bacteriophage T4-coded primase (gp61) with the T4 replication helicase (gp41) and DNA in primosome formation.

One primase (gp61) and six helicase (gp41) subunits interact to form the bacteriophage T4-coded primosome at the DNA replication fork. In order to map some of the detailed interactions of the primase within the primosome, we have constructed and characterized variants of the gp61 primase that carry kinase tags at either the N or the C terminus of the polypeptide chain. These tagged gp61 constructs have been probed using several analytical methods. Proteolytic digestion and protein kinase protection experiments show that specific interactions with single-stranded DNA and the T4 helicase hexamer significantly protect both the N- and the C-terminal regions of the T4 primase polypeptide chain against modification by these procedures and that this protection becomes more pronounced when the primase is assembled within the complete ternary primosome complex. Additional discrete sites of both protection and apparent hypersensitivity along the gp61 polypeptide chain have also been mapped by proteolytic footprinting reactions for the binary helicase-primase complex and in the three component primosome. These studies provide a detailed map of a number of gp61 contact positions within the primosome and reveal interactions that may be important in the structure and function of this central component of the T4 DNA replication complex.